Sample records for focal hippocampal seizures

  1. Unilateral or bilateral punctate hippocampal hyperintensities on DW-MRI: seizures, amnesia, or both?

    PubMed

    Bocos-Portillo, Jone; Escalza-Cortina, Inés; Gómez-Beldarrain, Marian; Rodriguez-Sainz, Aida; Garcia-Monco, Juan Carlos

    2018-06-02

    The presence of small hippocampal hyperintense lesions on diffusion-weighted (DW) MRI can respond to different etiologies and represents a challenge where clinical judgment is imperative, since therapeutic approach may be quite different.We here report three patients with similar neuroradiological findings, i.e., hyperintense punctate hippocampal lesions on diffusion-weighted MRI sequences, yet of different origin. The first one presented with isolated amnesia (transient global amnesia), the second one with amnesia and seizures, and the third one with seizures.Thus, hippocampal punctate lesions appear after transient global amnesia, but the same pattern may be present after seizures, either focal-onset or generalized seizures. This peculiar radiological MRI pattern could indicate a pathogenic link between transient global amnesia (TGA) and seizures which should be further studied.

  2. Partial (focal) seizure

    MedlinePlus

    ... Jacksonian seizure; Seizure - partial (focal); Temporal lobe seizure; Epilepsy - partial seizures ... Abou-Khalil BW, Gallagher MJ, Macdonald RL. Epilepsies. In: Daroff ... Practice . 7th ed. Philadelphia, PA: Elsevier; 2016:chap 101. ...

  3. Multiple hippocampal transections for intractable hippocampal epilepsy: Seizure outcome.

    PubMed

    Koubeissi, Mohamad Z; Kahriman, Emine; Fastenau, Philip; Bailey, Christopher; Syed, Tanvir; Amina, Shahram; Miller, Jonathan; Munyon, Charles; Tanner, Adriana; Karanec, Kristina; Tuxhorn, Ingrid; Lüders, Hans

    2016-05-01

    The purpose of this study was to evaluate the seizure outcomes after transverse multiple hippocampal transections (MHTs) in 13 patients with intractable TLE. Thirteen patients with normal memory scores, including 8 with nonlesional hippocampi on MRI, had temporal lobe epilepsy (TLE) necessitating depth electrode implantation. After confirming hippocampal seizure onset, they underwent MHT. Intraoperative monitoring was done with 5-6 hippocampal electrodes spaced at approximately 1-cm intervals and spike counting for 5-8min before each cut. The number of transections ranged between 4 and 7. Neuropsychological assessment was completed preoperatively and postoperatively for all patients and will be reported separately. Duration of epilepsy ranged between 5 and 55years. There were no complications. Intraoperatively, MHT resulted in marked spike reduction (p=0.003, paired t-test). Ten patients (77%) are seizure-free (average follow-up was 33months, range 20-65months) without medication changes. One of the 3 patients with persistent seizures had an MRI revealing incomplete transections, another had an additional neocortical seizure focus (as suggested by pure aphasic seizures), and the third had only 2 seizures in 4years, one of which occurred during antiseizure medication withdrawal. Verbal and visual memory outcomes will be reported separately. Right and left hippocampal volumes were not different preoperatively (n=12, p=0.64, Wilcoxon signed-rank test), but the transected hippocampal volume decreased postoperatively (p=0.0173). Multiple hippocampal transections provide an effective intervention and a safe alternative to temporal lobectomy in patients with hippocampal epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Seizure ending signs in patients with dyscognitive focal seizures.

    PubMed

    Gavvala, Jay R; Gerard, Elizabeth E; Macken, Mícheál; Schuele, Stephan U

    2015-09-01

    Signs indicating the end of a focal seizure with loss of awareness and/or responsiveness but without progression to focal or generalized motor symptoms are poorly defined and can be difficult to determine. Not recognizing the transition from ictal to postictal behaviour can affect seizure reporting accuracy by family members and may lead to delayed or a lack of examination during EEG monitoring, erroneous seizure localization and inadequate medical intervention for prolonged seizure duration. Our epilepsy monitoring unit database was searched for focal seizures without secondary generalization for the period from 2007 to 2011. The first focal seizure in a patient with loss of awareness and/or responsiveness and/or behavioural arrest, with or without automatisms, was included. Seizures without objective symptoms or inadequate video-EEG quality were excluded. A total of 67 patients were included, with an average age of 41.7 years. Thirty-six of the patients had seizures from the left hemisphere and 29 from the right. All patients showed an abrupt change in motor activity and resumed contact with the environment as a sign of clinical seizure ending. Specific ending signs (nose wiping, coughing, sighing, throat clearing, or laughter) were seen in 23 of 47 of temporal lobe seizures and 7 of 20 extra-temporal seizures. Seizure ending signs are often subtle and the most common finding is a sudden change in motor activity and resumption of contact with the environment. More distinct signs, such as nose wiping, coughing or throat clearing, are not specific to temporal lobe onset. A higher proportion of seizures during sleep went unexamined, compared to those during wakefulness. This demonstrates that seizure semiology can be very subtle and arousals from sleep during monitoring should alert staff. Patient accounts of seizure frequency appear to be unreliable and witness reports need to be taken into account. [Published with video sequences].

  5. Genetic (idiopathic) epilepsy with photosensitive seizures includes features of both focal and generalized seizures.

    PubMed

    Xue, Jiao; Gong, Pan; Yang, Haipo; Liu, Xiaoyan; Jiang, Yuwu; Zhang, Yuehua; Yang, Zhixian

    2018-04-19

    Clinically, some patients having genetic (idiopathic) epilepsy with photosensitive seizures were difficult to be diagnosed. We aimed to discuss whether the genetic (idiopathic) epilepsy with photosensitive seizures is a focal entity, a generalized entity or a continuum. Twenty-two patients with idiopathic epilepsies and photoconvulsive response (PCR) were retrospectively recruited. In the medical records, the seizure types included "generalized tonic-clonic seizures (GTCS)" in 15, "partial secondarily GTCS (PGTCS)" in 3, partial seizures (PS) in 3, myoclonic seizures in 2, eyelid myoclonus in one, and only febrile seizures in one. Seizure types of PCR included GTCS (1/22), PGTCS (6/22), PS (9/22), electrical seizures (ES) (3/22) and GTCS/PGTCS (3/22). Combined the medical history with PCR results, they were diagnosed as: idiopathic (photosensitive) occipital lobe epilepsy (I(P)OE) in 12, genetic (idiopathic) generalized epilepsy (GGE) in one, GGE/I(P)OE in 5, pure photosensitive seizure in one, and epilepsy with undetermined generalized or focal seizure in 3. So, the dichotomy between generalized and focal seizures might have been out of date regarding to pathophysiological advances in epileptology. To some extent, it would be better to recognize the idiopathic epilepsy with photosensitive seizures as a continuum between focal and generalized seizures.

  6. Chemical–genetic attenuation of focal neocortical seizures

    PubMed Central

    Kätzel, Dennis; Nicholson, Elizabeth; Schorge, Stephanie; Walker, Matthew C.; Kullmann, Dimitri M.

    2014-01-01

    Focal epilepsy is commonly pharmacoresistant, and resective surgery is often contraindicated by proximity to eloquent cortex. Many patients have no effective treatment options. Gene therapy allows cell-type specific inhibition of neuronal excitability, but on-demand seizure suppression has only been achieved with optogenetics, which requires invasive light delivery. Here we test a combined chemical–genetic approach to achieve localized suppression of neuronal excitability in a seizure focus, using viral expression of the modified muscarinic receptor hM4Di. hM4Di has no effect in the absence of its selective, normally inactive and orally bioavailable agonist clozapine-N-oxide (CNO). Systemic administration of CNO suppresses focal seizures evoked by two different chemoconvulsants, pilocarpine and picrotoxin. CNO also has a robust anti-seizure effect in a chronic model of focal neocortical epilepsy. Chemical–genetic seizure attenuation holds promise as a novel approach to treat intractable focal epilepsy while minimizing disruption of normal circuit function in untransduced brain regions or in the absence of the specific ligand. PMID:24866701

  7. Generalized onset seizures with focal evolution (GOFE) - A unique seizure type in the setting of generalized epilepsy.

    PubMed

    Linane, Avriel; Lagrange, Andre H; Fu, Cary; Abou-Khalil, Bassel

    2016-01-01

    We report clinical and electrographic features of generalized onset seizures with focal evolution (GOFE) and present arguments for the inclusion of this seizure type in the seizure classification. The adult and pediatric Epilepsy Monitoring Unit databases at Vanderbilt Medical Center and Children's Hospital were screened to identify generalized onset seizures with focal evolution. We reviewed medical records for epilepsy characteristics, epilepsy risk factors, MRI abnormalities, neurologic examination, antiepileptic medications before and after diagnosis, and response to medications. We also reviewed ictal and interictal EEG tracings, as well as video-recorded semiology. Ten patients were identified, 7 males and 3 females. All of the patients developed generalized epilepsy in childhood or adolescence (ages 3-15years). Generalized onset seizures with focal evolution developed years after onset in 9 patients, with a semiology concerning for focal seizures or nonepileptic events. Ictal discharges had a generalized onset on EEG, described as either generalized spike-and-wave and/or polyspike-and-wave discharges, or generalized fast activity. This electrographic activity then evolved to focal rhythmic activity most commonly localized to one temporal or frontal region; five patients had multiple seizures evolving to focal activity in different regions of both hemispheres. The predominant interictal epileptiform activity included generalized spike-and-wave and/or polyspike-and-wave discharges in all patients. Taking into consideration all clinical and EEG data, six patients were classified with genetic (idiopathic) generalized epilepsy, and four were classified with structural/metabolic (symptomatic) generalized epilepsy. All of the patients had modifications to their medications following discharge, with three becoming seizure-free and five responding with >50% reduction in seizure frequency. Generalized onset seizures may occasionally have focal evolution with semiology

  8. The semiology of febrile seizures: Focal features are frequent.

    PubMed

    Takasu, Michihiko; Kubota, Tetsuo; Tsuji, Takeshi; Kurahashi, Hirokazu; Numoto, Shingo; Watanabe, Kazuyoshi; Okumura, Akihisa

    2017-08-01

    To clarify the semiology of febrile seizures (FS) and to determine the frequency of FS with symptoms suggestive of focal onset. FS symptoms in children were reported within 24h of seizure onset by the parents using a structured questionnaire consisting principally of closed-ended questions. We focused on events at seizure commencement, including changes in behavior and facial expression, and ocular and oral symptoms. We also investigated the autonomic and motor symptoms developing during seizures. The presence or absence of focal and limbic features was determined for each patient. The associations of certain focal and limbic features with patient characteristics were assessed. Information was obtained on FS in 106 children. Various events were recorded at seizure commencement. Behavioral changes were observed in 35 children, changes in facial expression in 53, ocular symptoms in 78, and oral symptoms in 90. In terms of events during seizures, autonomic symptoms were recognized in 78, and convulsive motor symptoms were recognized in 68 children. Focal features were evident in 81 children; 38 children had two or more such features. Limbic features were observed in 44 children, 9 of whom had two or more such features. There was no significant relationship between any patient characteristic and the numbers of focal or limbic features. The semiology of FS varied widely among children, and symptoms suggestive of focal onset were frequent. FS of focal onset may be more common than is generally thought. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Mechanisms underlying different onset patterns of focal seizures

    PubMed Central

    Trevelyan, Andrew J; Valentin, Antonio; Alarcon, Gonzalo

    2017-01-01

    Focal seizures are episodes of pathological brain activity that appear to arise from a localised area of the brain. The onset patterns of focal seizure activity have been studied intensively, and they have largely been distinguished into two types—low amplitude fast oscillations (LAF), or high amplitude spikes (HAS). Here we explore whether these two patterns arise from fundamentally different mechanisms. Here, we use a previously established computational model of neocortical tissue, and validate it as an adequate model using clinical recordings of focal seizures. We then reproduce the two onset patterns in their most defining properties and investigate the possible mechanisms underlying the different focal seizure onset patterns in the model. We show that the two patterns are associated with different mechanisms at the spatial scale of a single ECoG electrode. The LAF onset is initiated by independent patches of localised activity, which slowly invade the surrounding tissue and coalesce over time. In contrast, the HAS onset is a global, systemic transition to a coexisting seizure state triggered by a local event. We find that such a global transition is enabled by an increase in the excitability of the “healthy” surrounding tissue, which by itself does not generate seizures, but can support seizure activity when incited. In our simulations, the difference in surrounding tissue excitability also offers a simple explanation of the clinically reported difference in surgical outcomes. Finally, we demonstrate in the model how changes in tissue excitability could be elucidated, in principle, using active stimulation. Taken together, our modelling results suggest that the excitability of the tissue surrounding the seizure core may play a determining role in the seizure onset pattern, as well as in the surgical outcome. PMID:28472032

  10. Prolonged Febrile Seizures in the Immature Rat Model Enhance Hippocampal Excitability Long Term

    PubMed Central

    Dube, Celine; Chen, Kang; Eghbal-Ahmadi, Mariam; Brunson, Kristen; Soltesz, Ivan; Baram, Tallie Z.

    2011-01-01

    Febrile seizures (FSs) constitute the most prevalent seizure type during childhood. Whether prolonged FSs alter limbic excitability, leading to spontaneous seizures (temporal lobe epilepsy) during adulthood, has been controversial. Recent data indicate that, in the immature rat model, prolonged FSs induce transient structural changes of some hippocampal pyramidal neurons and long-term functional changes of hippocampal circuitry. However, whether these neuroanatomical and electrophysiological changes promote hippocampal excitability and lead to epilepsy has remained unknown. By using in vivo and in vitro approaches, we determined that prolonged hyperthermia-induced seizures in immature rats caused long-term enhanced susceptibility to limbic convulsants that lasted to adulthood. Thus, extensive hippocampal electroencephalographic and behavioral monitoring failed to demonstrate spontaneous seizures in adult rats that had experienced hyperthermic seizures during infancy. However, 100% of animals developed hippocampal seizures after systemic administration of a low dose of kainate, and most progressed to status epilepticus. Conversely, a minority of normothermic and hyperthermic controls had (brief) seizures, none developing status epilepticus. In vitro, spontaneous epileptiform discharges were not observed in hippocampal-entorhinal cortex slices derived from either control or experimental groups. However, Schaeffer collateral stimulation induced prolonged, self-sustaining, status epilepticus-like discharges exclusively in slices from experimental rats. These data indicate that hyperthermic seizures in the immature rat model of FSs do not cause spontaneous limbic seizures during adulthood. However, they reduce thresholds to chemical convulsants in vivo and electrical stimulation in vitro, indicating persistent enhancement of limbic excitability that may facilitate the development of epilepsy. PMID:10716253

  11. Repeated seizures induce long-term increase in hippocampal benzodiazepine receptors.

    PubMed Central

    McNamara, J O; Peper, A M; Patrone, V

    1980-01-01

    Repeated seizures, whether induced by kindling or electroshock, caused a long-lasting (at least 24 hr) increase of [3H]diazepam binding in hippocampal membranes of Sprague-Dawley rats. Scatchard analyses demonstrated that increased numbers of binding sites accounted for the increase. Neither repeated hypoxia nor repeated administration of electrical current without inducing seizures caused an increase of [3H]diazepam binding. Regardless of the method used for seizure induction, the response was graded in that large numbers of seizures were required to induce significant increases, whereas fewer seizures induced only slight increases. We suggest that the receptor increases imply a heightened response to benzodiazepines and more powerful hippocampal recurrent inhibition. PMID:6930682

  12. Seizure prediction in hippocampal and neocortical epilepsy using a model-based approach

    PubMed Central

    Aarabi, Ardalan; He, Bin

    2014-01-01

    Objectives The aim of this study is to develop a model based seizure prediction method. Methods A neural mass model was used to simulate the macro-scale dynamics of intracranial EEG data. The model was composed of pyramidal cells, excitatory and inhibitory interneurons described through state equations. Twelve model’s parameters were estimated by fitting the model to the power spectral density of intracranial EEG signals and then integrated based on information obtained by investigating changes in the parameters prior to seizures. Twenty-one patients with medically intractable hippocampal and neocortical focal epilepsy were studied. Results Tuned to obtain maximum sensitivity, an average sensitivity of 87.07% and 92.6% with an average false prediction rate of 0.2 and 0.15/h were achieved using maximum seizure occurrence periods of 30 and 50 min and a minimum seizure prediction horizon of 10 s, respectively. Under maximum specificity conditions, the system sensitivity decreased to 82.9% and 90.05% and the false prediction rates were reduced to 0.16 and 0.12/h using maximum seizure occurrence periods of 30 and 50 min, respectively. Conclusions The spatio-temporal changes in the parameters demonstrated patient-specific preictal signatures that could be used for seizure prediction. Significance The present findings suggest that the model-based approach may aid prediction of seizures. PMID:24374087

  13. Termination of seizure clusters is related to the duration of focal seizures.

    PubMed

    Ferastraoaru, Victor; Schulze-Bonhage, Andreas; Lipton, Richard B; Dümpelmann, Matthias; Legatt, Alan D; Blumberg, Julie; Haut, Sheryl R

    2016-06-01

    Clustered seizures are characterized by shorter than usual interseizure intervals and pose increased morbidity risk. This study examines the characteristics of seizures that cluster, with special attention to the final seizure in a cluster. This is a retrospective analysis of long-term inpatient monitoring data from the EPILEPSIAE project. Patients underwent presurgical evaluation from 2002 to 2009. Seizure clusters were defined by the occurrence of at least two consecutive seizures with interseizure intervals of <4 h. Other definitions of seizure clustering were examined in a sensitivity analysis. Seizures were classified into three contextually defined groups: isolated seizures (not meeting clustering criteria), terminal seizure (last seizure in a cluster), and intracluster seizures (any other seizures within a cluster). Seizure characteristics were compared among the three groups in terms of duration, type (focal seizures remaining restricted to one hemisphere vs. evolving bilaterally), seizure origin, and localization concordance among pairs of consecutive seizures. Among 92 subjects, 77 (83%) had at least one seizure cluster. The intracluster seizures were significantly shorter than the last seizure in a cluster (p = 0.011), whereas the last seizure in a cluster resembled the isolated seizures in terms of duration. Although focal only (unilateral), seizures were shorter than seizures that evolved bilaterally and there was no correlation between the seizure type and the seizure position in relation to a cluster (p = 0.762). Frontal and temporal lobe seizures were more likely to cluster compared with other localizations (p = 0.009). Seizure pairs that are part of a cluster were more likely to have a concordant origin than were isolated seizures. Results were similar for the 2 h definition of clustering, but not for the 8 h definition of clustering. We demonstrated that intracluster seizures are short relative to isolated seizures and terminal seizures. Frontal

  14. Role of inhibitory control in modulating focal seizure spread.

    PubMed

    Liou, Jyun-You; Ma, Hongtao; Wenzel, Michael; Zhao, Mingrui; Baird-Daniel, Eliza; Smith, Elliot H; Daniel, Andy; Emerson, Ronald; Yuste, Rafael; Schwartz, Theodore H; Schevon, Catherine A

    2018-05-10

    Focal seizure propagation is classically thought to be spatially contiguous. However, distribution of seizures through a large-scale epileptic network has been theorized. Here, we used a multielectrode array, wide field calcium imaging, and two-photon calcium imaging to study focal seizure propagation pathways in an acute rodent neocortical 4-aminopyridine model. Although ictal neuronal bursts did not propagate beyond a 2-3-mm region, they were associated with hemisphere-wide field potential fluctuations and parvalbumin-positive interneuron activity outside the seizure focus. While bicuculline surface application enhanced contiguous seizure propagation, focal bicuculline microinjection at sites distant to the 4-aminopyridine focus resulted in epileptic network formation with maximal activity at the two foci. Our study suggests that both classical and epileptic network propagation can arise from localized inhibition defects, and that the network appearance can arise in the context of normal brain structure without requirement for pathological connectivity changes between sites.

  15. Seizures and Sleep in the Thalamus: Focal Limbic Seizures Show Divergent Activity Patterns in Different Thalamic Nuclei

    PubMed Central

    Feng, Li; Motelow, Joshua E.; Ma, Chanthia; Liu, Mengran; Zhan, Qiong; Jia, Ruonan; Xiao, Bo; Duque, Alvaro

    2017-01-01

    The thalamus plays diverse roles in cortical-subcortical brain activity patterns. Recent work suggests that focal temporal lobe seizures depress subcortical arousal systems and convert cortical activity into a pattern resembling slow-wave sleep. The potential simultaneous and paradoxical role of the thalamus in both limbic seizure propagation, and in sleep-like cortical rhythms has not been investigated. We recorded neuronal activity from the central lateral (CL), anterior (ANT), and ventral posteromedial (VPM) nuclei of the thalamus in an established female rat model of focal limbic seizures. We found that population firing of neurons in CL decreased during seizures while the cortex exhibited slow waves. In contrast, ANT showed a trend toward increased neuronal firing compatible with polyspike seizure discharges seen in the hippocampus. Meanwhile, VPM exhibited a remarkable increase in sleep spindles during focal seizures. Single-unit juxtacellular recordings from CL demonstrated reduced overall firing rates, but a switch in firing pattern from single spikes to burst firing during seizures. These findings suggest that different thalamic nuclei play very different roles in focal limbic seizures. While limbic nuclei, such as ANT, appear to participate directly in seizure propagation, arousal nuclei, such as CL, may contribute to depressed cortical function, whereas sleep spindles in relay nuclei, such as VPM, may interrupt thalamocortical information flow. These combined effects could be critical for controlling both seizure severity and impairment of consciousness. Further understanding of differential effects of seizures on different thalamocortical networks may lead to improved treatments directly targeting these modes of impaired function. SIGNIFICANCE STATEMENT Temporal lobe epilepsy has a major negative impact on quality of life. Previous work suggests that the thalamus plays a critical role in thalamocortical network modulation and subcortical arousal

  16. Efficacy of lacosamide by focal seizure subtype.

    PubMed

    Sperling, Michael R; Rosenow, Felix; Faught, Edward; Hebert, David; Doty, Pamela; Isojärvi, Jouko

    2014-10-01

    The purpose of this post hoc exploratory analysis was to determine the effects of the antiepileptic drug, lacosamide, on focal (partial-onset) seizure subtypes. Patient data from the three lacosamide pivotal trials were grouped and pooled by focal seizure subtype at Baseline: simple partial seizures (SPS), complex partial seizures (CPS), and secondarily generalized partial seizures (SGPS). Both efficacy outcomes (median percent change from Baseline to Maintenance Phase in seizure frequency per 28 days and the proportion of patients experiencing at least a 50% reduction in seizures) were evaluated by lacosamide dose (200, 400, or 600 mg/day) compared to placebo for each seizure subtype. An additional analysis was performed to determine whether a shift from more severe focal seizure subtypes to less severe occurred upon treatment with lacosamide. In patients with CPS or SGPS at Baseline, lacosamide 400 mg/day (maximum recommended daily dose) and 600 mg/day reduced the frequency of CPS and SGPS compared to placebo. Likewise, a proportion of patients with CPS and SGPS at Baseline experienced at least a 50% reduction in the frequency of CPS and SGPS (≥50% responder rate) in the lacosamide 400 and 600 mg/day groups compared with placebo. For both outcomes, numerically greatest responses were observed in the lacosamide 600 mg/day group among patients with SGPS at Baseline. In patients with SPS at Baseline, no difference between placebo and lacosamide was observed for either efficacy outcome. An additional exploratory analysis suggests that in patients with SPS at Baseline, CPS and SGPS may have been shifted to less severe SPS upon treatment with lacosamide. The results of these exploratory analyses revealed reductions in CPS and SGPS frequency with adjunctive lacosamide. Reduction in CPS and SGPS may confound assessment of SPS since the CPS or SGPS may possibly change to SPS by effective treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Various ketogenic diets can differently support brain resistance against experimentally evoked seizures and seizure-induced elemental anomalies of hippocampal formation.

    PubMed

    Chwiej, J; Patulska, A; Skoczen, A; Matusiak, K; Janeczko, K; Ciarach, M; Simon, R; Setkowicz, Z

    2017-07-01

    In this paper the influence of two different ketogenic diets (KDs) on the seizure-evoked elemental anomalies of hippocampal formation was examined. To achieve this purpose normal and pilocarpine treated rats previously fed with one of the two high fat and carbohydrate restricted diets were compared with animals on standard laboratory diet. The ketogenic ratios of the examined KDs were equal to 5:1 (KD1) and 9:1 (KD2). KD1 and standard diet fed animals presented similar patterns of seizure-evoked elemental changes in hippocampal formation. Also the analysis of behavioral data recorded after pilocarpine injection did not show any significant differences in intensity and duration of seizures between KD1 and standard diet fed animals. Higher ketogenic ratio KD2 introduced in the normal hippocampal formation prolonged changes in the accumulation of P, K, Zn and Ca. Despite this, both the intensity and duration of seizures were significantly reduced in rats fed with KD2 which suggests that its saving action on the nerve tissue may protect brain from seizure propagation. Also seizure-evoked elemental anomalies in KD2 animals were different than those observed for rats both on KD1 and standard diets. The comparison of seizure experiencing and normal rats on KD2, did not show any statistically significant differences in elemental composition of CA1 and H hippocampal areas whilst in CA3 area only Zn level changed as a result of seizures. DG was the area mostly affected by seizures in KD2 fed rats but areal densities of all examined elements increased in this hippocampal region. Copyright © 2017 Elsevier GmbH. All rights reserved.

  18. Seizures and Sleep in the Thalamus: Focal Limbic Seizures Show Divergent Activity Patterns in Different Thalamic Nuclei.

    PubMed

    Feng, Li; Motelow, Joshua E; Ma, Chanthia; Biche, William; McCafferty, Cian; Smith, Nicholas; Liu, Mengran; Zhan, Qiong; Jia, Ruonan; Xiao, Bo; Duque, Alvaro; Blumenfeld, Hal

    2017-11-22

    The thalamus plays diverse roles in cortical-subcortical brain activity patterns. Recent work suggests that focal temporal lobe seizures depress subcortical arousal systems and convert cortical activity into a pattern resembling slow-wave sleep. The potential simultaneous and paradoxical role of the thalamus in both limbic seizure propagation, and in sleep-like cortical rhythms has not been investigated. We recorded neuronal activity from the central lateral (CL), anterior (ANT), and ventral posteromedial (VPM) nuclei of the thalamus in an established female rat model of focal limbic seizures. We found that population firing of neurons in CL decreased during seizures while the cortex exhibited slow waves. In contrast, ANT showed a trend toward increased neuronal firing compatible with polyspike seizure discharges seen in the hippocampus. Meanwhile, VPM exhibited a remarkable increase in sleep spindles during focal seizures. Single-unit juxtacellular recordings from CL demonstrated reduced overall firing rates, but a switch in firing pattern from single spikes to burst firing during seizures. These findings suggest that different thalamic nuclei play very different roles in focal limbic seizures. While limbic nuclei, such as ANT, appear to participate directly in seizure propagation, arousal nuclei, such as CL, may contribute to depressed cortical function, whereas sleep spindles in relay nuclei, such as VPM, may interrupt thalamocortical information flow. These combined effects could be critical for controlling both seizure severity and impairment of consciousness. Further understanding of differential effects of seizures on different thalamocortical networks may lead to improved treatments directly targeting these modes of impaired function. SIGNIFICANCE STATEMENT Temporal lobe epilepsy has a major negative impact on quality of life. Previous work suggests that the thalamus plays a critical role in thalamocortical network modulation and subcortical arousal

  19. Theta frequency decreases throughout the hippocampal formation in a focal epilepsy model.

    PubMed

    Kilias, Antje; Häussler, Ute; Heining, Katharina; Froriep, Ulrich P; Haas, Carola A; Egert, Ulrich

    2018-06-01

    Mesial temporal lobe epilepsy is characterized by focal, recurrent spontaneous seizures, sclerosis and granule cell dispersion (GCD) in the hippocampal formation. Changes in theta rhythm properties have been correlated with the severity of hippocampal restructuring and were suggested as a cause of memory deficits accompanying epilepsy. For severe sclerosis, it has even been questioned whether theta band oscillations persist. We asked how theta oscillations change with graded restructuring along the longitudinal hippocampal axis and whether these changes correlate with the overall severity of temporal lobe epilepsy. We recorded local field potentials in the medial entorhinal cortex and along the septo-temporal axis of the dentate gyrus at sites with different degrees of GCD in freely behaving epileptic mice. Theta frequency was decreased at all recording positions throughout the dentate gyrus and in the medial entorhinal cortex, irrespective of the extent of GCD or the rate of severe epileptic events. The frequency reduction by up to 1.7 Hz, corresponding to 1/3 octaves within the theta range, was present during rest, exploration and running. Despite the frequency reduction, theta oscillations remained coherent across the hippocampal formation and were modulated by running speed as in controls. The reduction in theta frequency thus is likely not a consequence of the local restructuring but rather a global phenomenon affecting the hippocampal formation as a whole. © 2018 Wiley Periodicals, Inc.

  20. Rapid focal cooling attenuates cortical seizures in a primate epilepsy model.

    PubMed

    Ren, Guoping; Yan, Jiaqing; Tao, Guoxian; Gan, Yunmeng; Li, Donghong; Yan, Xi; Fu, Yongjuan; Wang, Leiming; Wang, Weimin; Zhang, Zhiming; Yue, Feng; Yang, Xiaofeng

    2017-09-01

    Rapid focal cooling is an attractive nondestructive strategy to control and possibly prevent focal seizures. However, the temperature threshold necessary to abort seizures in primates is still unknown. Here, we explored this issue in a primate epilepsy model and observed the effect of rapid cooling on different electroencephalogram frequency bands, aiming at providing necessary experimental data for future clinical translational studies and exploring the mechanism of focal cooling in terminating seizures. We induced focal neocortical seizures using microinjection of 4-aminopyridine into premotor cortex in five anesthetized cynomolgus monkeys. The rapid focal cooling was implemented by using a thermoelectric (Peltier) device. As a result, the average durations of seizures and interictal intervals before cooling were 94.3±4.0s and 62.3±6.9s, respectively. When the cortex was cooled to 20°C or 18°C, there was no effect on seizure duration (109.4±30.0s, 91.3±19.3s) or interictal duration (99.4±26.8s, 83.2±11.5s, P>0.05). But when the cortex was cooled to 16°C, the seizure duration was reduced to 54.1±4.9s and the interictal duration was extended to 175.0±16.7s (P<0.05). Electroencephalogram spectral analysis showed that the power of delta, alpha, beta, gamma and ripples bands in seizures were significantly reduced at 20°C and 18°C. At 16°C, the power of theta band in seizures was also significantly reduced along with the other bands. Our data reveal that the temperature threshold in rapid focal cooling required to significantly shorten neocortical seizures in nonhuman primates is 16°C, and inhibition of electroencephalogram broadband spectrum power, especially power of theta band, may be the underlying mechanism to control seizures. Copyright © 2017. Published by Elsevier Inc.

  1. Prediction of secondary generalization from a focal onset seizure in intracerebral EEG.

    PubMed

    Karthick, P A; Tanaka, Hideaki; Khoo, Hui Ming; Gotman, Jean

    2018-05-01

    We propose a system based on the first five seconds of intracerebrally recorded focal seizures to predict their evolution from focal to bilateral tonic-clonic seizure (FTC), to spread outside the onset zone but without tonic-clonic component (FS), or to a seizure remaining focal (F). Nineteen time and frequency domain features were extracted from 39 seizures of 32 patients and were subjected to support vector machine based classification. Three prediction approaches regarding seizure evolution were (1) FTC vs FS vs F, (2) FTC vs FS or F and (3) FTC or FS vs F. We used 21 seizures for training. Most features had significantly different distributions in the three seizure types (p < 0.05). Eighteen seizures were used for testing. We predicted the evolution of 12 seizures in FTC vs FS vs F, 13 seizures in FTC vs FS or F and 14 seizures in FTC or FS vs F. The first five seconds of a focal seizure contains information regarding the eventual evolution of the seizure, which could be predicted in most seizures. The proposed system could alert the health care team when a patient is hospitalized for intracerebral EEG and improve safety and eventually result in an implantable device. Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  2. Epilepsy, hippocampal sclerosis and febrile seizures linked by common genetic variation around SCN1A

    PubMed Central

    Kasperavičiūtė, Dalia; Catarino, Claudia B.; Matarin, Mar; Leu, Costin; Novy, Jan; Tostevin, Anna; Leal, Bárbara; Hessel, Ellen V. S.; Hallmann, Kerstin; Hildebrand, Michael S.; Dahl, Hans-Henrik M.; Ryten, Mina; Trabzuni, Daniah; Ramasamy, Adaikalavan; Alhusaini, Saud; Doherty, Colin P.; Dorn, Thomas; Hansen, Jörg; Krämer, Günter; Steinhoff, Bernhard J.; Zumsteg, Dominik; Duncan, Susan; Kälviäinen, Reetta K.; Eriksson, Kai J.; Kantanen, Anne-Mari; Pandolfo, Massimo; Gruber-Sedlmayr, Ursula; Schlachter, Kurt; Reinthaler, Eva M.; Stogmann, Elisabeth; Zimprich, Fritz; Théâtre, Emilie; Smith, Colin; O’Brien, Terence J.; Meng Tan, K.; Petrovski, Slave; Robbiano, Angela; Paravidino, Roberta; Zara, Federico; Striano, Pasquale; Sperling, Michael R.; Buono, Russell J.; Hakonarson, Hakon; Chaves, João; Costa, Paulo P.; Silva, Berta M.; da Silva, António M.; de Graan, Pierre N. E.; Koeleman, Bobby P. C.; Becker, Albert; Schoch, Susanne; von Lehe, Marec; Reif, Philipp S.; Rosenow, Felix; Becker, Felicitas; Weber, Yvonne; Lerche, Holger; Rössler, Karl; Buchfelder, Michael; Hamer, Hajo M.; Kobow, Katja; Coras, Roland; Blumcke, Ingmar; Scheffer, Ingrid E.; Berkovic, Samuel F.; Weale, Michael E.; Delanty, Norman; Depondt, Chantal; Cavalleri, Gianpiero L.; Kunz, Wolfram S.

    2013-01-01

    Epilepsy comprises several syndromes, amongst the most common being mesial temporal lobe epilepsy with hippocampal sclerosis. Seizures in mesial temporal lobe epilepsy with hippocampal sclerosis are typically drug-resistant, and mesial temporal lobe epilepsy with hippocampal sclerosis is frequently associated with important co-morbidities, mandating the search for better understanding and treatment. The cause of mesial temporal lobe epilepsy with hippocampal sclerosis is unknown, but there is an association with childhood febrile seizures. Several rarer epilepsies featuring febrile seizures are caused by mutations in SCN1A, which encodes a brain-expressed sodium channel subunit targeted by many anti-epileptic drugs. We undertook a genome-wide association study in 1018 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 7552 control subjects, with validation in an independent sample set comprising 959 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 3591 control subjects. To dissect out variants related to a history of febrile seizures, we tested cases with mesial temporal lobe epilepsy with hippocampal sclerosis with (overall n = 757) and without (overall n = 803) a history of febrile seizures. Meta-analysis revealed a genome-wide significant association for mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures at the sodium channel gene cluster on chromosome 2q24.3 [rs7587026, within an intron of the SCN1A gene, P = 3.36 × 10−9, odds ratio (A) = 1.42, 95% confidence interval: 1.26–1.59]. In a cohort of 172 individuals with febrile seizures, who did not develop epilepsy during prospective follow-up to age 13 years, and 6456 controls, no association was found for rs7587026 and febrile seizures. These findings suggest SCN1A involvement in a common epilepsy syndrome, give new direction to biological understanding of mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures

  3. Detection of recurrent activation patterns across focal seizures: Application to seizure onset zone identification.

    PubMed

    Vila-Vidal, Manel; Principe, Alessandro; Ley, Miguel; Deco, Gustavo; Tauste Campo, Adrià; Rocamora, Rodrigo

    2017-06-01

    We introduce a method that quantifies the consistent involvement of intracranially monitored regions in recurrent focal seizures. We evaluated the consistency of two ictal spectral activation patterns (mean power change and power change onset time) in intracranial recordings across focal seizures from seven patients with clinically marked seizure onset zone (SOZ). We examined SOZ discrimination using both patterns in different frequency bands and periods of interest. Activation patterns were proved to be consistent across more than 80% of recurrent ictal epochs. In all patients, whole-seizure mean activations were significantly higher for SOZ than non-SOZ regions (P<0.05) while activation onset times were significantly lower for SOZ than for non-SOZ regions (P<0.001) in six patients. Alpha-beta bands (8-20Hz) achieved the highest patient-average effect size on the whole-seizure period while gamma band (20-70Hz) achieved the highest discrimination values between SOZ and non-SOZ sites near seizure onset (0-5s). Consistent spectral activation patterns in focal epilepsies discriminate the SOZ with high effect sizes upon appropriate selection of frequency bands and activation periods. The present method may be used to improve epileptogenic identification as well as pinpoint additional regions that are functionally altered during ictal events. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  4. Classic hippocampal sclerosis and hippocampal-onset epilepsy produced by a single “cryptic” episode of focal hippocampal excitation in awake rats

    PubMed Central

    Norwood, Braxton A.; Bumanglag, Argyle V.; Osculati, Francesco; Sbarbati, Andrea; Marzola, Pasquina; Nicolato, Elena; Fabene, Paolo F.; Sloviter, Robert S.

    2010-01-01

    In refractory temporal lobe epilepsy, seizures often arise from a shrunken hippocampus exhibiting a pattern of selective neuron loss called “classic hippocampal sclerosis.” No single experimental injury has reproduced this specific pathology, suggesting that hippocampal atrophy might be a progressive “endstage” pathology resulting from years of spontaneous seizures. We posed the alternate hypothesis that classic hippocampal sclerosis results from a single excitatory event that has never been successfully modeled experimentally because convulsive status epilepticus, the insult most commonly used to produce epileptogenic brain injury, is too severe and necessarily terminated before the hippocampus receives the needed duration of excitation. We tested this hypothesis by producing prolonged hippocampal excitation in awake rats without causing convulsive status epilepticus. Two daily 30-minute episodes of perforant pathway stimulation in Sprague-Dawley rats increased granule cell paired-pulse inhibition, decreased epileptiform afterdischarge durations during 8 hours of subsequent stimulation, and prevented convulsive status epilepticus. Similarly, one 8-hour episode of reduced-intensity stimulation in Long-Evans rats, which are relatively resistant to developing status epilepticus, produced hippocampal discharges without causing status epilepticus. Both paradigms immediately produced the extensive neuronal injury that defines classic hippocampal sclerosis, without giving any clinical indication during the insult that an injury was being inflicted. Spontaneous hippocampal-onset seizures began 16–25 days post-injury, before hippocampal atrophy developed, as demonstrated by sequential magnetic resonance imaging. These results indicate that classic hippocampal sclerosis is uniquely produced by a single episode of clinically “cryptic” excitation. Epileptogenic insults may often involve prolonged excitation that goes undetected at the time of injury. PMID

  5. Effects of undernourishment, recurrent seizures and enriched environment during early life in hippocampal morphology.

    PubMed

    Alvarez, Paula Steffen; Simão, Fabrício; Hemb, Marta; Xavier, Léder Leal; Nunes, Magda Lahorgue

    2014-04-01

    It has been recently shown that enriched environment led to a significant benefit in learning and retention of visual-spatial memory, being able to reverse the cognitive impairment generated by undernourishment and recurrent seizures. We investigated the hippocampal morphological effects of recurrent seizures and undernourishment early in life in Wistar rats and the possible benefits produced by the enriched environment in these conditions. The morphological parameters stereologically evaluated were hippocampal volume, thickness of pyramidal stratum of the CA1 subfield and neuronal and glial densities in the same subfield. Male Wistar rats were divided into eight groups including nourished, nourished+enriched environment, nourished+recurrent seizures, nourished+recurrent seizures+enriched environment, undernourished, undernourished+enriched environment, undernourished+recurrent seizures and undernourished+recurrent seizures+enriched environment. Undernourishment model consisted in nutritional deprivation regimen from post-natal day 2 (P2) to P15. From P8 to P10, recurrent seizures group were induced by flurothyl three times per day. Enriched environment groups were exposed between P21 and P51. Our main findings were: (1) animals submitted to the enriched environment showed an increased hippocampal volume; (2) enriched environment promotes increases in the thickness of the pyramidal layer in hippocampal CA1 subfield in animals nourished and undernourished with recurrent seizures; (3) undernourishment during early development decreased neuronal density in CA1 and CA3 subfields. Our findings show that these three conditions induces important changes in hippocampal morphology, the most deleterious changes are induced by undernourishment and recurrent seizures, while more beneficial morphological changes are produced by enriched environment. Copyright © 2014 ISDN. Published by Elsevier Ltd. All rights reserved.

  6. Familial aggregation of focal seizure semiology in the Epilepsy Phenome/Genome Project.

    PubMed

    Tobochnik, Steven; Fahlstrom, Robyn; Shain, Catherine; Winawer, Melodie R

    2017-07-04

    To improve phenotype definition in genetic studies of epilepsy, we assessed the familial aggregation of focal seizure types and of specific seizure symptoms within the focal epilepsies in families from the Epilepsy Phenome/Genome Project. We studied 302 individuals with nonacquired focal epilepsy from 149 families. Familial aggregation was assessed by logistic regression analysis of relatives' traits (dependent variable) by probands' traits (independent variable), estimating the odds ratio for each symptom in a relative given presence vs absence of the symptom in the proband. In families containing multiple individuals with nonacquired focal epilepsy, we found significant evidence for familial aggregation of ictal motor, autonomic, psychic, and aphasic symptoms. Within these categories, ictal whole body posturing, diaphoresis, dyspnea, fear/anxiety, and déjà vu/jamais vu showed significant familial aggregation. Focal seizure type aggregated as well, including complex partial, simple partial, and secondarily generalized tonic-clonic seizures. Our results provide insight into genotype-phenotype correlation in the nonacquired focal epilepsies and a framework for identifying subgroups of patients likely to share susceptibility genes. © 2017 American Academy of Neurology.

  7. Bilateral hippocampal atrophy in temporal lobe epilepsy: Effect of depressive symptoms and febrile seizures

    PubMed Central

    Finegersh, Andrey; Avedissian, Christina; Shamim, Sadat; Dustin, Irene; Thompson, Paul M.; Theodore, William H.

    2011-01-01

    Summary Purpose Neuroimaging studies suggest a history of febrile seizures, and depression, are associated with hippocampal volume reductions in patients with temporal lobe epilepsy (TLE). Methods We used radial atrophy mapping (RAM), a three-dimensional (3D) surface modeling tool, to measure hippocampal atrophy in 40 patients with unilateral TLE, with or without a history of febrile seizures and symptoms of depression. Multiple linear regression was used to single out the effects of covariates on local atrophy. Key Findings Subjects with a history of febrile seizures (n = 15) had atrophy in regions corresponding to the CA1 and CA3 subfields of the hippocampus contralateral to seizure focus (CHC) compared to those without a history of febrile seizures (n = 25). Subjects with Beck Depression Inventory II (BDI-II) score ≥14 (n = 11) had atrophy in the superoanterior portion of the CHC compared to subjects with BDI-II <14 (n = 29). Significance Contralateral hippocampal atrophy in TLE may be related to febrile seizures or depression. PMID:21269286

  8. Effects of Antiepileptic Drugs on Spontaneous Recurrent Seizures in a Novel Model of Extended Hippocampal Kindling in Mice

    PubMed Central

    Song, Hongmei; Tufa, Uilki; Chow, Jonathan; Sivanenthiran, Nila; Cheng, Chloe; Lim, Stellar; Wu, Chiping; Feng, Jiachun; Eubanks, James H.; Zhang, Liang

    2018-01-01

    Epilepsy is a common neurological disorder characterized by naturally-occurring spontaneous recurrent seizures and comorbidities. Kindling has long been used to model epileptogenic mechanisms and to assess antiepileptic drugs. In particular, extended kindling can induce spontaneous recurrent seizures without gross brain lesions, as seen clinically. To date, the development of spontaneous recurrent seizures following extended kindling, and the effect of the antiepileptic drugs on these seizures are not well understood. In the present study we aim to develop a mouse model of extended hippocampal kindling for the first time. Once established, we plan to evaluate the effect of three different antiepileptic drugs on the development of the extended-hippocampal-kindled-induced spontaneous recurrent seizures. Male C57 black mice were used for chronic hippocampal stimulations or handling manipulations (twice daily for up to 70 days). Subsequently, animals underwent continuous video/EEG monitoring for seizure detection. Spontaneous recurrent seizures were consistently observed in extended kindled mice but no seizures were detected in the control animals. The aforementioned seizures were generalized events characterized by hippocampal ictal discharges and concurrent motor seizures. Incidence and severity of the seizures was relatively stable while monitored over a few months after termination of the hippocampal stimulation. Three antiepileptic drugs with distinct action mechanisms were tested: phenytoin, lorazepam and levetiracetam. They were applied via intra-peritoneal injections at anticonvulsive doses and their effects on the spontaneous recurrent seizures were analyzed 10–12 h post-injection. Phenytoin (25 mg/kg) and levetiracetam (400 mg/kg) abolished the spontaneous recurrent seizures. Lorazepam (1.5 mg/kg) decreased motor seizure severity but did not reduce the incidence and duration of corresponding hippocampal discharges, implicating its inhibitory effects on

  9. Effects of Antiepileptic Drugs on Spontaneous Recurrent Seizures in a Novel Model of Extended Hippocampal Kindling in Mice.

    PubMed

    Song, Hongmei; Tufa, Uilki; Chow, Jonathan; Sivanenthiran, Nila; Cheng, Chloe; Lim, Stellar; Wu, Chiping; Feng, Jiachun; Eubanks, James H; Zhang, Liang

    2018-01-01

    Epilepsy is a common neurological disorder characterized by naturally-occurring spontaneous recurrent seizures and comorbidities. Kindling has long been used to model epileptogenic mechanisms and to assess antiepileptic drugs. In particular, extended kindling can induce spontaneous recurrent seizures without gross brain lesions, as seen clinically. To date, the development of spontaneous recurrent seizures following extended kindling, and the effect of the antiepileptic drugs on these seizures are not well understood. In the present study we aim to develop a mouse model of extended hippocampal kindling for the first time. Once established, we plan to evaluate the effect of three different antiepileptic drugs on the development of the extended-hippocampal-kindled-induced spontaneous recurrent seizures. Male C57 black mice were used for chronic hippocampal stimulations or handling manipulations (twice daily for up to 70 days). Subsequently, animals underwent continuous video/EEG monitoring for seizure detection. Spontaneous recurrent seizures were consistently observed in extended kindled mice but no seizures were detected in the control animals. The aforementioned seizures were generalized events characterized by hippocampal ictal discharges and concurrent motor seizures. Incidence and severity of the seizures was relatively stable while monitored over a few months after termination of the hippocampal stimulation. Three antiepileptic drugs with distinct action mechanisms were tested: phenytoin, lorazepam and levetiracetam. They were applied via intra-peritoneal injections at anticonvulsive doses and their effects on the spontaneous recurrent seizures were analyzed 10-12 h post-injection. Phenytoin (25 mg/kg) and levetiracetam (400 mg/kg) abolished the spontaneous recurrent seizures. Lorazepam (1.5 mg/kg) decreased motor seizure severity but did not reduce the incidence and duration of corresponding hippocampal discharges, implicating its inhibitory effects on

  10. Synchronous inhibitory potentials precede seizure-like events in acute models of focal limbic seizures.

    PubMed

    Uva, Laura; Breschi, Gian Luca; Gnatkovsky, Vadym; Taverna, Stefano; de Curtis, Marco

    2015-02-18

    Interictal spikes in models of focal seizures and epilepsies are sustained by the synchronous activation of glutamatergic and GABAergic networks. The nature of population spikes associated with seizure initiation (pre-ictal spikes; PSs) is still undetermined. We analyzed the networks involved in the generation of both interictal and PSs in acute models of limbic cortex ictogenesis induced by pharmacological manipulations. Simultaneous extracellular and intracellular recordings from both principal cells and interneurons were performed in the medial entorhinal cortex of the in vitro isolated guinea pig brain during focal interictal and ictal discharges induced in the limbic network by intracortical and brief arterial infusions of either bicuculline methiodide (BMI) or 4-aminopyridine (4AP). Local application of BMI in the entorhinal cortex did not induce seizure-like events (SLEs), but did generate periodic interictal spikes sensitive to the glutamatergic non-NMDA receptor antagonist DNQX. Unlike local applications, arterial perfusion of either BMI or 4AP induced focal limbic SLEs. PSs just ahead of SLE were associated with hyperpolarizing potentials coupled with a complete blockade of firing in principal cells and burst discharges in putative interneurons. Interictal population spikes recorded from principal neurons between two SLEs correlated with a depolarizing potential. We demonstrate in two models of acute limbic SLE that PS events are different from interictal spikes and are sustained by synchronous activation of inhibitory networks. Our findings support a prominent role of synchronous network inhibition in the initiation of a focal seizure. Copyright © 2015 the authors 0270-6474/15/353048-08$15.00/0.

  11. Management of focal-onset seizures: an update on drug treatment.

    PubMed

    Johannessen, Svein I; Ben-Menachem, Elinor

    2006-01-01

    Focal-onset seizures are manifestations of abnormal epileptic firing of brain cells in a localised area or areas of the brain. The diagnosis of focal-onset seizures initially entails an EEG, a detailed history from the patient and eyewitnesses, as well as computer tomographic or, preferably, magnetic resonance imaging scans. Video EEG to record ictal events may be necessary to establish the correct diagnosis. Focal seizures are classified according to the International Classification of Epileptic Seizures and International Classification of Epilepsies and Epilepsy Syndromes. It is important to try to decide how the seizure event fits into this system in order to successfully evaluate and optimise treatment, as well as to give detailed information to the patient about their seizures and prognosis. Once the decision to treat the seizures has been made, the physician must choose which medication is the most appropriate to begin with. Carbamazepine, phenytoin or valproic acid (sodium valproate) are often rated as first-line drugs, but factors such as adverse-effect profiles, age, possibility of pregnancy, and concomitant diseases and medication also need to be considered. Most of the newer antiepileptic drugs (AEDs) appear to have good efficacy and better tolerability than the older agents, but evidence to support their superiority is scarce and has led to conflicting advice in several guidelines. Among the newer AEDs, lamotrigine, gabapentin, topiramate and oxcarbazepine have obtained monotherapy indication in many countries. The higher costs of the newer AEDs may inhibit their wider use, especially in poorer countries.

  12. Seizure Freedom in Children With Pathology-Confirmed Focal Cortical Dysplasia.

    PubMed

    Mrelashvili, Anna; Witte, Robert J; Wirrell, Elaine C; Nickels, Katherine C; Wong-Kisiel, Lily C

    2015-12-01

    We evaluated the temporal course of seizure outcome in children with pathology-confirmed focal cortical dysplasia and explored predictors of sustained seizure freedom. We performed a single-center retrospective study of children ≤ 18 years who underwent resective surgery from January 1, 2000 through December 31, 2012 and had pathology-proven focal cortical dysplasia. Surgical outcome was classified as seizure freedom (Engel class I) or seizure recurrence (Engel classes II-IV). Fisher exact and nonparametric Wilcoxon ranksum tests were used, as appropriate. Survival analysis was based on seizure-free outcome. Patients were censored at the time of seizure recurrence or seizure freedom at last follow-up. Thirty-eight patients were identified (median age at surgery, 6.5 years; median duration of epilepsy, 3.3 years). Median time to last follow-up was 13.5 months (interquartile range, 7-41 months). Twenty patients (53%) were seizure free and 26 patients (68%) attained seizure freedom for a minimum of 3 months. Median time to seizure recurrence was 38 months (95% confidence interval, 6-109 months), and the cumulative seizure-free rate was 60% at 12 months (95% confidence interval, 43%-77%). Clinical features associated with seizure freedom at last follow-up included older age at seizure onset (P = .02), older age at surgery (P = .04), absent to mild intellectual disability before surgery (P = .05), and seizure freedom for a minimum of 3 months (P < .001). Favorable clinical features associated with sustained seizure freedom included older age at seizure onset, older age at surgery, absent or mild intellectual disability at baseline, and seizure freedom for a minimum of 3 months. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Epilepsy of infancy with migrating focal seizures: three patients treated with the ketogenic diet.

    PubMed

    Caraballo, Roberto; Noli, Daniel; Cachia, Pedro

    2015-06-01

    We present three patients with epilepsy of infancy with migrating focal seizures treated with the ketogenic diet. Between February 1, 2012 and January 31, 2014, three patients who met the diagnostic criteria for migrating focal seizures in infancy at our department were placed on the ketogenic diet and followed for a minimum of seven months. Two of the three children responded well to the ketogenic diet. One of these patients became seizure-free and his neuropsychological performance also significantly improved. The other child had a seizure reduction of 75% to 99% with only weekly seizures and moderate psychomotor improvement. For these two patients who responded well to the ketogenic diet, hospital admission was not required. The remaining patient had a seizure reduction of less than 50%. Tolerability of the diet was good in all three patients. Early treatment with the ketogenic diet should be considered for epilepsy of infancy with migrating focal seizures to control seizures and status epilepticus, and avoid progressive cognitive impairment.

  14. Silent hippocampal seizures and spikes identified by foramen ovale electrodes in Alzheimer's disease.

    PubMed

    Lam, Alice D; Deck, Gina; Goldman, Alica; Eskandar, Emad N; Noebels, Jeffrey; Cole, Andrew J

    2017-06-01

    We directly assessed mesial temporal activity using intracranial foramen ovale electrodes in two patients with Alzheimer's disease (AD) without a history or EEG evidence of seizures. We detected clinically silent hippocampal seizures and epileptiform spikes during sleep, a period when these abnormalities were most likely to interfere with memory consolidation. The findings in these index cases support a model in which early development of occult hippocampal hyperexcitability may contribute to the pathogenesis of AD.

  15. Risk of seizure relapse after antiepileptic drug withdrawal in adult patients with focal epilepsy.

    PubMed

    He, Ru-Qian; Zeng, Qing-Yi; Zhu, Pan; Bao, Yi-Xin; Zheng, Rong-Yuan; Xu, Hui-Qin

    2016-11-01

    The objective of this study was to estimate the risk of a seizure relapse and the high-risk period of recurrence after antiepileptic drug (AED) withdrawal and to determine the predictive factors for a seizure relapse in adult patients with focal epilepsy who were seizure-free for more than 2years. Using the Wenzhou Epilepsy Follow-Up Registry Database, 200 adult patients with focal epilepsy were recruited, who were undergoing follow-up, met the inclusion criteria of this study, were seizure-free for more than 2years, began withdrawing between June 2003 and June 2014, and were followed up prospectively for at least 1year or until a seizure relapse. The risk of recurrence and the time to seizure relapse were analyzed by the Kaplan-Meier method, and the predictive factors were identified by the Cox proportional hazard regression model. A total of 99 patients had an unprovoked relapse during the follow-up period. The relapse rate was 49.5%, and each year, the recurrence probability of 12, 24, 36, 48, 60, 72, and 84months after AED withdrawal was 24.0%, 20.4%, 8.3%, 2.7%, 4.6%, 0.97%, and 0.98%, respectively. The two independent risk factors for recurrence after withdrawal in adult patients with focal epilepsy were a longer duration of active epilepsy and a shorter seizure-free period before withdrawal. The high-risk period of a seizure relapse in adult patients with focal epilepsy is the first 2years after withdrawal, and beyond 5years after withdrawal, seizures rarely relapse (relapse rate<1%). A seizure-free period for less than 4years before withdrawal is a predictive factor of risk for seizure recurrence after AED withdrawal in adult patients with focal epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Decreased subcortical cholinergic arousal in focal seizures

    PubMed Central

    Motelow, Joshua E.; Li, Wei; Zhan, Qiong; Mishra, Asht M.; Sachdev, Robert N. S.; Liu, Geoffrey; Gummadavelli, Abhijeet; Zayyad, Zaina; Lee, Hyun Seung; Chu, Victoria; Andrews, John P.; Englot, Dario J.; Herman, Peter; Sanganahalli, Basavaraju G.; Hyder, Fahmeed; Blumenfeld, Hal

    2015-01-01

    SUMMARY Impaired consciousness in temporal lobe seizures has a major negative impact on quality of life. The prevailing view holds that this disorder impairs consciousness by seizure spread to the bilateral temporal lobes. We propose instead that seizures invade subcortical regions and depress arousal, causing impairment through decreases rather than through increases in activity. Using functional magnetic resonance imaging in a rodent model, we found increased activity in regions known to depress cortical function including lateral septum and anterior hypothalamus. Importantly, we found suppression of intralaminar thalamic and brainstem arousal systems and suppression of the cortex. At a cellular level, we found reduced firing of identified cholinergic neurons in the brainstem pedunculopontine tegmental nucleus and basal forebrain. Finally, we used enzyme-based amperometry to demonstrate reduced cholinergic neurotransmission in both cortex and thalamus. Decreased subcortical arousal is a novel mechanism for loss of consciousness in focal temporal lobe seizures. PMID:25654258

  17. Lacosamide: A Review in Focal Seizures in Patients with Epilepsy.

    PubMed

    Scott, Lesley J

    2015-12-01

    Lacosamide (Vimpat(®)) is a functionalized amino acid available orally (as a solution or tablets) and as an intravenous infusion for use as monotherapy (only in the USA) or adjunctive therapy for the treatment of focal seizures in adult and adolescent (aged ≥17 years in the USA) patients with epilepsy. As adjunctive therapy to other antiepileptic drugs (AEDs), lacosamide provided effective seizure control and was generally well tolerated in adults and adolescents (aged ≥16 years) in randomized clinical trials and in the real-world setting. In clinical trials, adjunctive lacosamide provided significantly greater reductions in 28-day seizure rates than adjunctive placebo, with these benefits maintained after up to 8 years of therapy in open-label extension studies. Moreover, patients were effectively switched from oral to short-term intravenous adjunctive therapy at the same dosage, which may be particularly beneficial in situations where oral therapy is not suitable. Conversion to lacosamide monotherapy was superior to a historical-control cohort in patients with focal seizures converting from previous AED therapy. In the absence of head-to-head comparisons with other AEDs, the exact position of lacosamide relative to other AEDs remains to be fully determined. In the meantime, oral and intravenous lacosamide provides a useful option as monotherapy (only in the USA) or adjunctive therapy for the treatment of focal seizures in adult and adolescent (aged ≥17 years in the USA) patients with epilepsy.

  18. Memory impairment is not necessarily related to seizure frequency in mesial temporal lobe epilepsy with hippocampal sclerosis.

    PubMed

    Pacagnella, Denise; Lopes, Tatila M; Morita, Marcia E; Yasuda, Clarissa L; Cappabianco, Fabio A M; Bergo, Felipe; Balthazar, Marcio L F; Coan, Ana C; Cendes, Fernando

    2014-08-01

    To investigate the effect of seizure frequency on memory, we performed a cross sectional study comparing mesial temporal lobe epilepsy (MTLE) patients with frequent and infrequent seizures. We performed magnetic resonance imaging (MRI) hippocampal volume (HV) measurements and neuropsychological assessment in 22 patients with frequent seizures (at least one dyscognitive seizure [DS] per month) that were refractory to antiepileptic drugs and 20 patients with infrequent seizures (three or less DS per year and no event evolving to a bilateral convulsive seizure), all with MRI signs of hippocampal sclerosis (HS) on visual analysis. We also included 29 controls for comparison of volumetric data. There was no difference in memory performance between patients with frequent seizures and infrequent seizures. We observed a significant bilateral reduction of HV in patients with MTLE when compared to controls (p < 0.001). The degree of hippocampal atrophy (HA) between patients with frequent and infrequent seizures was not different. There was a negative correlation between seizure frequency and HV, with r = -0.3 for the HV ipsilateral to the HS and r = -0.55 for the contralateral side, thus, explaining only 9% and 30% of the HV loss. There was a positive correlation between age of onset and degree of HA (r = 0.37). Our data suggest that seizure frequency does not explain most of the HV loss or memory impairment in MTLE. Memory impairment appears to be more influenced by hippocampal damage than by seizure frequency. Further studies are necessary to identify the factors that influence memory decline in patients with MTLE. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

  19. Temporal lobe dual pathology in malignant migrating partial seizures in infancy.

    PubMed

    Coppola, Giangennaro; Operto, Francesca Felicia; Auricchio, Gianfranca; D'Amico, Alessandra; Fortunato, Delia; Pascotto, Antonio

    2007-06-01

    A child had the characteristic clinical and EEG pattern of migrating partial seizures in infancy with left temporal lobe atrophy, hippocampal sclerosis and cortical-subcortical blurring. Seizures were drug-resistant, with recurring episodes of status epilepticus. The child developed microcephaly with arrest of psychomotor development. Focal brain lesions, in the context of migrating partial seizures, have not been previously reported.[Published with video sequences].

  20. Brain State Is a Major Factor in Preseizure Hippocampal Network Activity and Influences Success of Seizure Intervention

    PubMed Central

    Ewell, Laura A.; Liang, Liang; Armstrong, Caren; Soltész, Ivan; Leutgeb, Stefan

    2015-01-01

    Neural dynamics preceding seizures are of interest because they may shed light on mechanisms of seizure generation and could be predictive. In healthy animals, hippocampal network activity is shaped by behavioral brain state and, in epilepsy, seizures selectively emerge during specific brain states. To determine the degree to which changes in network dynamics before seizure are pathological or reflect ongoing fluctuations in brain state, dorsal hippocampal neurons were recorded during spontaneous seizures in a rat model of temporal lobe epilepsy. Seizures emerged from all brain states, but with a greater likelihood after REM sleep, potentially due to an observed increase in baseline excitability during periods of REM compared with other brains states also characterized by sustained theta oscillations. When comparing the firing patterns of the same neurons across brain states associated with and without seizures, activity dynamics before seizures followed patterns typical of the ongoing brain state, or brain state transitions, and did not differ until the onset of the electrographic seizure. Next, we tested whether disparate activity patterns during distinct brain states would influence the effectiveness of optogenetic curtailment of hippocampal seizures in a mouse model of temporal lobe epilepsy. Optogenetic curtailment was significantly more effective for seizures preceded by non-theta states compared with seizures that emerged from theta states. Our results indicate that consideration of behavioral brain state preceding a seizure is important for the appropriate interpretation of network dynamics leading up to a seizure and for designing effective seizure intervention. SIGNIFICANCE STATEMENT Hippocampal single-unit activity is strongly shaped by behavioral brain state, yet this relationship has been largely ignored when studying activity dynamics before spontaneous seizures in medial temporal lobe epilepsy. In light of the increased attention on using single

  1. Focal seizure symptoms in idiopathic generalized epilepsies.

    PubMed

    Seneviratne, Udaya; Woo, Jia J; Boston, Ray C; Cook, Mark; D'Souza, Wendyl

    2015-08-18

    We sought to study the frequency and prognostic value of focal seizure symptoms (FSS) in idiopathic generalized epilepsies (IGE) using a validated tool: Epilepsy Diagnostic Interview Questionnaire and Partial Seizure Symptom Definitions. Participants with IGE were recruited from epilepsy clinics at 2 tertiary hospitals. The diagnosis was validated and classified into syndromes according to the International League Against Epilepsy criteria by 2 epileptologists independently with discordance resolved by consensus. The Epilepsy Diagnostic Interview Questionnaire utilizes both open- and closed-ended questions to elicit FSS in association with generalized tonic-clonic seizures, myoclonus, and absences. The elicited FSS were classified according to the Partial Seizure Symptom Definitions. Regression analysis was conducted to examine the relationship between the duration of seizure freedom and FSS. A total of 135 patients were studied, of whom 70 (51.9%) reported FSS. Those symptoms occurred in association with generalized tonic-clonic seizures (53.1%) as well as myoclonus and absences (58%). FSS were reported with similar frequency in juvenile absence epilepsy (62.5%) and juvenile myoclonic epilepsy (60%), and with a lesser frequency in generalized epilepsy with tonic-clonic seizures only (39.5%) and childhood absence epilepsy (33.3%). A strong relationship between FSS and duration of seizure freedom was found (regression coefficient -0.665, p = 0.037). FSS are frequently reported by patients with IGE. A shorter duration of seizure freedom is associated with FSS. Recognition of the presence of FSS in IGE is important to avoid misdiagnosis and delayed diagnosis as well as to choose appropriate antiepileptic drug therapy. © 2015 American Academy of Neurology.

  2. Noninvasive transcranial focal stimulation via tripolar concentric ring electrodes lessens behavioral seizure activity of recurrent pentylenetetrazole administrations in rats.

    PubMed

    Makeyev, Oleksandr; Luna-Munguía, Hiram; Rogel-Salazar, Gabriela; Liu, Xiang; Besio, Walter G

    2013-05-01

    Epilepsy affects approximately 1% of the world population. Antiepileptic drugs are ineffective in approximately 30% of patients and have side effects. We have been developing a noninvasive transcranial focal electrical stimulation with our novel tripolar concentric ring electrodes as an alternative/complementary therapy for seizure control. In this study we demonstrate the effect of focal stimulation on behavioral seizure activity induced by two successive pentylenetetrazole administrations in rats. Seizure onset latency, time of the first behavioral change, duration of seizure, and maximal seizure severity score were studied and compared for focal stimulation treated (n = 9) and control groups (n = 10). First, we demonstrate that no significant difference was found in behavioral activity for focal stimulation treated and control groups after the first pentylenetetrazole administration. Next, comparing first and second pentylenetetrazole administrations, we demonstrate there was a significant change in behavioral activity (time of the first behavioral change) in both groups that was not related to focal stimulation. Finally, we demonstrate focal stimulation provoking a significant change in seizure onset latency, duration of seizure, and maximal seizure severity score. We believe that these results, combined with our previous reports, suggest that transcranial focal stimulation may have an anticonvulsant effect.

  3. Interaction between synaptic inhibition and glial-potassium dynamics leads to diverse seizure transition modes in biophysical models of human focal seizures.

    PubMed

    Y Ho, E C; Truccolo, Wilson

    2016-10-01

    How focal seizures initiate and evolve in human neocortex remains a fundamental problem in neuroscience. Here, we use biophysical neuronal network models of neocortical patches to study how the interaction between inhibition and extracellular potassium ([K (+)] o ) dynamics may contribute to different types of focal seizures. Three main types of propagated focal seizures observed in recent intracortical microelectrode recordings in humans were modelled: seizures characterized by sustained (∼30-60 Hz) gamma local field potential (LFP) oscillations; seizures where the onset in the propagated site consisted of LFP spikes that later evolved into rhythmic (∼2-3 Hz) spike-wave complexes (SWCs); and seizures where a brief stage of low-amplitude fast-oscillation (∼10-20 Hz) LFPs preceded the SWC activity. Our findings are fourfold: (1) The interaction between elevated [K (+)] o (due to abnormal potassium buffering by glial cells) and the strength of synaptic inhibition plays a predominant role in shaping these three types of seizures. (2) Strengthening of inhibition leads to the onset of sustained narrowband gamma seizures. (3) Transition into SWC seizures is obtained either by the weakening of inhibitory synapses, or by a transient strengthening followed by an inhibitory breakdown (e.g. GABA depletion). This reduction or breakdown of inhibition among fast-spiking (FS) inhibitory interneurons increases their spiking activity and leads them eventually into depolarization block. Ictal spike-wave discharges in the model are then sustained solely by pyramidal neurons. (4) FS cell dynamics are also critical for seizures where the evolution into SWC activity is preceded by low-amplitude fast oscillations. Different levels of elevated [K (+)] o were important for transitions into and maintenance of sustained gamma oscillations and SWC discharges. Overall, our modelling study predicts that the interaction between inhibitory interneurons and [K (+)] o glial buffering under

  4. [Different effects of chronically administered phenobarbital on amygdaloid- and hippocampal-kindled seizures in the cat].

    PubMed

    Sumi, T

    1993-03-01

    Kindling model has been regarded as an experimental model for partial seizure with secondary generalized convulsion in human epilepsy. A number of pharmacological studies have been carried out to evaluate antiepileptic effects of conventional anticonvulsants on kindled seizures, mainly using amygdala kindled model. However, it is known that hippocampus is a more important site for human temporal epilepsy. It should therefore be considered appropriate to evaluate effects of antiepileptic drugs, not only on amygdaloid- but also on hippocampal-kindled seizures. In the present study, effects of chronically administered phenobarbital (PB) on amygdaloid- and hippocampal-kindled seizures were investigated. In the first session, cats were orally administered 6 mg/kg of PB for 15 days to obtain the serum level between 15 micrograms/ml and 25 micrograms/ml (optimal level for human epileptic seizure), then stimulation was carried out once a day for the following five days with suprathreshold stimulation intensity (100 microA higher than generalized seizure triggering threshold). For evaluation of drug efficacy, duration of afterdischarge and seizure severity were determined. After the end of session 1, session 2 started with 12 mg/kg of PB for 35-50 micrograms/ml serum level (subtoxic level) and continued in the same manner as stated above. PB was proved to be more effective for hippocampal- than for amygdaloid-kindled seizures. Generalized convulsions were easily suppressed in the level of 15-25 micrograms/ml and afterdischarge was totally suppressed in 33% of cats in the level of 35-50 micrograms/ml in the hippocampal-kindled group. However, amygdaloid-kindled seizures were more resistant to PB. It was difficult to suppress generalized convulsion in the level of 15-25 micrograms/ml, and total suppression of afterdischarge was extremely rare even in the higher serum level in amygdaloid-kindled cats. In addition, cats requiring a smaller number of stimuli to the completion of

  5. Regional cerebral blood flow changes associated with focal electrically administered seizure therapy (FEAST).

    PubMed

    Chahine, George; Short, Baron; Spicer, Ken; Schmidt, Matthew; Burns, Carol; Atoui, Mia; George, Mark S; Sackeim, Harold A; Nahas, Ziad

    2014-01-01

    Use of electroconvulsive therapy (ECT) is limited by cognitive disturbance. Focal electrically-administered seizure therapy (FEAST) is designed to initiate focal seizures in the prefrontal cortex. To date, no studies have documented the effects of FEAST on regional cerebral blood flow (rCBF). A 72 year old depressed man underwent three single photon emission computed tomography (SPECT) scans to capture the onset and resolution of seizures triggered with right unilateral FEAST. We used Bioimage Suite for within-subject statistical analyses of perfusion differences ictally and post-ictally compared with the baseline scan. Early ictal increases in regional cerebral blood flow (rCBF) were limited to the right prefrontal cortex. Post-ictally, perfusion was reduced in bilateral frontal and occipital cortices and increased in left motor and precuneus cortex. FEAST appears to triggers focal onsets of seizure activity in the right prefrontal cortex with subsequent generalization. Future studies are needed on a larger sample. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Effect of Temporal Neocortical Pathology on Seizure Freeness in Adult Patients with Temporal Lobe Epilepsy.

    PubMed

    Kemerdere, Rahsan; Ahmedov, Merdin Lyutviev; Alizada, Orkhan; Yeni, Seher Naz; Oz, Buge; Tanriverdi, Taner

    2018-05-23

    Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy. Focal cortical dysplasia is the most common dual pathology found in association with the hippocampal sclerosis. In this study, the effect of dual pathology on freedom from seizure was sought in patients with TLE. This study performed a retrospective analysis of patients with TLE who underwent surgery between 2010 and 2017. Histopathologic analysis was performed on patients with and without dual pathology in the temporal neocortex. Seizure outcomes were compared. A total of 54 patients with TLE were included. The rate of overall favorable seizure outcome was found to be 96.3%. In 53.7%, dual pathology was present in the temporal cortices in addition to the hippocampal sclerosis. Patients without dual pathology showed significantly greater freedom from seizure (P = 0.02). Patients without dual pathology had a significantly higher seizure-free rate after anterior temporal resection than patients with dual pathology. Resection of the temporal cortex in addition to mesial temporal structures seems to be reasonable for better seizure outcome. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Outcomes of resective surgery in children and adolescents with focal lesional epilepsy: The experience of a tertiary epilepsy center.

    PubMed

    Hirfanoglu, Tugba; Serdaroglu, Ayse; Kurt, Gokhan; Erdem, Atilla; Capraz, Irem; Bilir, Erhan; Vural, Ozge; Ucar, Murat; Oner, Ali Yusuf; Onal, Baran; Akdemir, Ozgur; Atay, Ozlem; Arhan, Ebru; Aydin, Kursad

    2016-10-01

    This study aimed to investigate the efficacy of resective surgery in children with focal lesional epilepsy by evaluating the predictive value of pre- and postsurgical factors in terms of seizure freedom. This study included 61 children aged between 2 and 18years who were admitted to the pediatric video-EEG unit for presurgical workup. Each patient was evaluated with a detailed history, video-EEG, neuroimaging, and postsurgical outcomes according to Engel classification to predict postsurgical seizure freedom. All the possible factors including history, etiology, presurgical evaluation, surgical procedures, and postsurgical results were analyzed for their predictive value for postoperative seizure freedom. Of the 61 patients, 75% were diagnosed as having temporal lobe epilepsy (TLE), and 25% were diagnosed with extra-TLE. Two years after the surgery, 78.6% were seizure-free, of which 89% had TLE, and 50% had extra-TLE (p<0.05). Patients were more likely to have a favorable outcome for seizure freedom if they had rare seizure frequency, focal EEG findings, and focal seizures; had a temporal epileptogenic zone; or had TLE and hippocampal sclerosis. On the other hand, patients were more likely to have unfavorable results for seizure freedom if they had younger age of seizure onset, frequent seizures before the surgery, a frontal or multilobar epileptogenic zone, secondarily generalized seizures, extra-TLE with frontal lobe surgery, or focal cortical dysplasia. Resective surgery is one of the most effective treatment methods in children with intractable epilepsy. A history of young age of seizure onset, frequent seizures before surgery, secondarily generalized seizures, a multilobar epileptogenic zone, frontal lobe surgery, and focal cortical dysplasia (FCD) are the most important predictive factors indicating that a patient would continue having seizures after surgery. On the other hand, focal seizure semiologies, temporal lobe localization, and hippocampal sclerosis

  8. Prenatal choline deficiency does not enhance hippocampal vulnerability after kainic acid-induced seizures in adulthood

    PubMed Central

    Wong-Goodrich, Sarah J.E.; Tognoni, Christina M.; Mellott, Tiffany J.; Glenn, Melissa J.; Blusztajn, Jan K.; Williams, Christina L.

    2011-01-01

    Choline is a vital nutrient needed during early development for both humans and rodents. Severe dietary choline deficiency during pregnancy leads to birth defects, while more limited deficiency during mid- to late pregnancy causes deficits in hippocampal plasticity in adult rodent offspring that are accompanied by cognitive deficits only when task demands are high. Because prenatal choline supplementation confers neuroprotection of the adult hippocampus against a variety of neural insults and aids memory, we hypothesized that prenatal choline deficiency may enhance vulnerability to neural injury. To examine this, adult offspring of rat dams either fed a control diet (CON) or one deficient in choline (DEF) during embryonic days 12–17 were given multiple injections (i.p.) of saline (control) or kainic acid to induce seizures and were euthanized 16 days later. Perhaps somewhat surprisingly, DEF rats were not more susceptible to seizure induction and showed similar levels of seizure-induced hippocampal histopathology, GAD expression loss, upregulated hippocampal GFAP and growth factor expression, and increased dentate cell and neuronal proliferation as that seen in CON rats. Although prenatal choline deficiency compromises adult hippocampal plasticity in the intact brain, it does not appear to exacerbate the neuropathological response to seizures in the adult hippocampus at least shortly after excitotoxic injury. PMID:21840511

  9. Noninvasive transcranial focal stimulation via tripolar concentric ring electrodes lessens behavioral seizure activity of recurrent pentylenetetrazole administrations in rats

    PubMed Central

    Makeyev, Oleksandr; Luna-Munguía, Hiram; Rogel-Salazar, Gabriela; Liu, Xiang; Besio, Walter G.

    2012-01-01

    Epilepsy affects approximately one percent of the world population. Antiepileptic drugs are ineffective in approximately 30% of patients and have side effects. We have been developing a noninvasive transcranial focal electrical stimulation with our novel tripolar concentric ring electrodes as an alternative/complementary therapy for seizure control. In this study we demonstrate the effect of focal stimulation on behavioral seizure activity induced by two successive pentylenetetrazole administrations in rats. Seizure onset latency, time of the first behavioral change, duration of seizure, and maximal seizure severity score were studied and compared for focal stimulation treated (n = 9) and control groups (n = 10). First, we demonstrate that no significant difference was found in behavioral activity for focal stimulation treated and control groups after the first pentylenetetrazole administration. Next, comparing first and second pentylenetetrazole administrations, we demonstrate there was a significant change in behavioral activity (time of the first behavioral change) in both groups that was not related to focal stimulation. Finally, we demonstrate focal stimulation provoking a significant change in seizure onset latency, duration of seizure, and maximal seizure severity score. We believe that these results, combined with our previous reports, suggest that transcranial focal stimulation may have an anticonvulsant effect. PMID:22692938

  10. Repetitive convulsant-induced seizures reduce the number but not precision of hippocampal place cells.

    PubMed

    Lin, Hai; Hangya, Balázs; Fox, Steven E; Muller, Robert U

    2012-03-21

    Repetitive one-per-day seizures induced in otherwise normal rats by the volatile convulsant flurothyl decrease the accuracy of locating a hidden goal without changing the mean location of goal selection. We now show that an 8-d series of such seizures degrades the spatial signal carried by the firing of hippocampal pyramidal cells and specifically reduces the information conveyed by the place cell subset of pyramidal cells. This degradation and a concomitant slowing of the hippocampal theta rhythm occur over time courses parallel to the development of the behavioral deficit and plausibly account for the impairment. The details of how pyramidal cell discharge weakens are, however, unexpected. Rather than a reduction in the precision of location-specific firing distributed evenly over all place cells, the number of place cells decreases with seizure number, although the remaining place cells remain quite intact. Thus, with serial seizures there is a cell-specific conversion of robust place cells to sporadically firing (<0.1 spike/s) "low-rate" cells as opposed to gradual loss of place cell resolution. This transformation occurs in the absence of significant changes in the discharge rate of hippocampal interneurons, suggesting that the decline in the number of place cells is not a simple matter of increased inhibitory tone. The cumulative transformation of place cells to low-rate cells by repetitive seizures may reflect a homeostatic, negative-feedback process.

  11. Brivaracetam: a novel antiepileptic drug for focal-onset seizures.

    PubMed

    Stephen, Linda J; Brodie, Martin J

    2018-01-01

    Brivaracetam (BRV), the n -propyl analogue of levetiracetam (LEV), is the latest antiepileptic drug (AED) to be licensed in Europe and the USA for the adjunctive treatment of focal-onset seizures with or without secondary generalization in patients aged 16 years or older. Like LEV, BRV binds to synaptic vesicle protein 2A (SV2A), but BRV has more selective binding and a 15- to 30-fold higher binding affinity than LEV. BRV is more effective than LEV in slowing synaptic vesicle mobilization and the two AEDs may act at different binding sites or interact with different conformational states of the SV2A protein. In animal models, BRV provides protection against focal and secondary generalized seizures and has significant anticonvulsant effects in genetic models of epilepsy. The drug undergoes first-order pharmacokinetics with an elimination half-life of 7-8 h. Although BRV is metabolized extensively, the main circulating compound is unchanged BRV. Around 95% of metabolites undergo renal elimination. No dose reduction is required in renal impairment, but it is recommended that the daily dose is reduced by one-third in hepatic dysfunction that may prolong half-life. BRV has a low potential for drug interactions. The efficacy and tolerability of adjunctive BRV in adults with focal-onset seizures have been explored in six randomized, placebo-controlled studies. These showed significant efficacy outcomes for doses of 50-200 mg/day. The most common adverse events reported were headache, somnolence, dizziness, fatigue and nausea. Patients who develop psychiatric symptoms with LEV appear to be at risk of similar side effects with BRV, although preliminary data suggest that these issues are likely to be less frequent and perhaps less severe. As with all AEDs, a low starting dose and slow titration schedule help to minimize side effects and optimize seizure control and thereby quality of life.

  12. Microscale Spatiotemporal Dynamics during Neocortical Propagation of Human Focal Seizures

    PubMed Central

    Wagner, Fabien B.; Eskandar, Emad N.; Cosgrove, G. Rees; Madsen, Joseph R.; Blum, Andrew S.; Potter, N. Stevenson; Hochberg, Leigh R.; Cash, Sydney S.; Truccolo, Wilson

    2015-01-01

    Some of the most clinically consequential aspects of focal epilepsy, e.g. loss of consciousness, arise from the generalization or propagation of seizures through local and large-scale neocortical networks. Yet, the dynamics of such neocortical propagation remain poorly understood. Here, we studied the microdynamics of focal seizure propagation in neocortical patches (4 × 4 mm) recorded via high-density microelectrode arrays (MEAs) implanted in people with pharmacologically resistant epilepsy. Our main findings are threefold: (1) A newly developed stage segmentation method, applied to local field potentials (LFPs) and multi-unit activity (MUA), revealed a succession of discrete seizure stages, each lasting several seconds. These different stages showed characteristic evolutions in overall activity and spatial patterns, which were relatively consistent across seizures within each of the 5 patients studied. Interestingly, segmented seizure stages based on LFPs or MUA showed a dissociation of their spatiotemporal dynamics, likely reflecting different contributions of non-local synaptic inputs and local network activity. (2) As previously reported, some of the seizures showed a peak in MUA that happened several seconds after local seizure onset and slowly propagated across the MEA. However, other seizures had a more complex structure characterized by, for example, several MUA peaks, more consistent with the succession of discrete stages than the slow propagation of a simple wavefront of increased MUA. In both cases, nevertheless, seizures characterized by spike-wave discharges (SWDs, ~ 2–3Hz) eventually evolved into patterns of phase-locked MUA and LFPs. (3) Individual SWDs or gamma oscillation cycles (25–60 Hz), characteristic of two different types of recorded seizures, tended to propagate with varying degrees of directionality, directions of propagation and speeds, depending on the identified seizure stage. However, no clear relationship was observed between the

  13. Prenatal choline deficiency does not enhance hippocampal vulnerability after kainic acid-induced seizures in adulthood.

    PubMed

    Wong-Goodrich, Sarah J E; Tognoni, Christina M; Mellott, Tiffany J; Glenn, Melissa J; Blusztajn, Jan K; Williams, Christina L

    2011-09-21

    Choline is a vital nutrient needed during early development for both humans and rodents. Severe dietary choline deficiency during pregnancy leads to birth defects, while more limited deficiency during mid- to late pregnancy causes deficits in hippocampal plasticity in adult rodent offspring that are accompanied by cognitive deficits only when task demands are high. Because prenatal choline supplementation confers neuroprotection of the adult hippocampus against a variety of neural insults and aids memory, we hypothesized that prenatal choline deficiency may enhance vulnerability to neural injury. To examine this, adult offspring of rat dams either fed a control diet (CON) or one deficient in choline (DEF) during embryonic days 12-17 were given multiple injections (i.p.) of saline (control) or kainic acid to induce seizures and were euthanized 16 days later. Perhaps somewhat surprisingly, DEF rats were not more susceptible to seizure induction and showed similar levels of seizure-induced hippocampal histopathology, GAD expression loss, upregulated hippocampal GFAP and growth factor expression, and increased dentate cell and neuronal proliferation as that seen in CON rats. Although prenatal choline deficiency compromises adult hippocampal plasticity in the intact brain, it does not appear to exacerbate the neuropathological response to seizures in the adult hippocampus at least shortly after excitotoxic injury. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Focal BOLD-fMRI changes in bicuculline-induced tonic-clonic seizures in the rat

    PubMed Central

    DeSalvo, Matthew N.; Schridde, Ulrich; Mishra, Asht M.; Motelow, Joshua E.; Purcaro, Michael J.; Danielson, Nathan; Bai, Xiaoxiao; Hyder, Fahmeed; Blumenfeld, Hal

    2010-01-01

    Generalized tonic-clonic seizures cause widespread physiological changes throughout the cerebral cortex and subcortical structures in the brain. Using combined blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) at 9.4 T and electroencephalography (EEG) these changes can be characterized with high spatiotemporal resolution. We studied BOLD changes in anesthetized Wistar rats during bicuculline-induced tonic-clonic seizures. Bicuculline, a GABAA receptor antagonist, was injected systemically and seizure activity was observed on EEG as high amplitude, high-frequency polyspike discharges followed by clonic paroxysmal activity of lower frequency, with mean electrographic seizure duration of 349 s. Our aim was to characterize the spatial localization, direction, and timing of BOLD signal changes during the pre-ictal, ictal and post-ictal periods. Group analysis was performed across seizures using paired t-maps of BOLD signal superimposed on high resolution anatomical images. Regional analysis was then performed using volumes of interest to quantify BOLD timecourses. In the pre-ictal period we found focal BOLD increases in specific areas of somatosensory cortex (S1, S2) and thalamus several seconds before seizure onset. During seizures we observed BOLD increases in cortex, brainstem and thalamus and BOLD decreases in the hippocampus. The largest ictal BOLD increases remained in the focal regions of somatosensory cortex showing pre-ictal increases. During the post-ictal period we observed widespread BOLD decreases. These findings support a model in which “generalized” tonic-clonic seizures begin with focal changes before electrographic seizure onset, which progress to non-uniform changes during seizures, possibly shedding light on the etiology and pathophysiology of similar seizures in humans. PMID:20079442

  15. Repetitive Convulsant-Induced Seizures Reduce the Number But Not Precision of Hippocampal Place Cells

    PubMed Central

    Hangya, Balázs; Fox, Steven E.

    2012-01-01

    Repetitive one-per-day seizures induced in otherwise normal rats by the volatile convulsant flurothyl decrease the accuracy of locating a hidden goal without changing the mean location of goal selection. We now show that an 8-d series of such seizures degrades the spatial signal carried by the firing of hippocampal pyramidal cells and specifically reduces the information conveyed by the place cell subset of pyramidal cells. This degradation and a concomitant slowing of the hippocampal theta rhythm occur over time courses parallel to the development of the behavioral deficit and plausibly account for the impairment. The details of how pyramidal cell discharge weakens are, however, unexpected. Rather than a reduction in the precision of location-specific firing distributed evenly over all place cells, the number of place cells decreases with seizure number, although the remaining place cells remain quite intact. Thus, with serial seizures there is a cell-specific conversion of robust place cells to sporadically firing (<0.1 spike/s) “low-rate” cells as opposed to gradual loss of place cell resolution. This transformation occurs in the absence of significant changes in the discharge rate of hippocampal interneurons, suggesting that the decline in the number of place cells is not a simple matter of increased inhibitory tone. The cumulative transformation of place cells to low-rate cells by repetitive seizures may reflect a homeostatic, negative-feedback process. PMID:22442080

  16. Evolution of genuine cross-correlation strength of focal onset seizures.

    PubMed

    Müller, Markus F; Baier, Gerold; Jiménez, Yurytzy López; Marín García, Arlex O; Rummel, Christian; Schindler, Kaspar

    2011-10-01

    To quantify the evolution of genuine zero-lag cross-correlations of focal onset seizures, we apply a recently introduced multivariate measure to broad band and to narrow-band EEG data. For frequency components below 12.5 Hz, the strength of genuine cross-correlations decreases significantly during the seizure and the immediate postseizure period, while higher frequency bands show a tendency of elevated cross-correlations during the same period. We conclude that in terms of genuine zero-lag cross-correlations, the electrical brain activity as assessed by scalp electrodes shows a significant spatial fragmentation, which might promote seizure offset.

  17. Acute postoperative seizures and long-term seizure outcome after surgery for hippocampal sclerosis.

    PubMed

    Di Gennaro, Giancarlo; Casciato, Sara; Quarato, Pier Paolo; Mascia, Addolorata; D'Aniello, Alfredo; Grammaldo, Liliana G; De Risi, Marco; Meldolesi, Giulio N; Romigi, Andrea; Esposito, Vincenzo; Picardi, Angelo

    2015-01-01

    To assess the incidence and the prognostic value of acute postoperative seizures (APOS) in patients surgically treated for drug-resistant temporal lobe epilepsy due to hippocampal sclerosis (TLE-HS). We studied 139 consecutive patients with TLE-HS who underwent epilepsy surgery and were followed up for at least 5 years (mean duration of follow-up 9.1 years, range 5-15). Medical charts were reviewed to identify APOS, defined as ictal events with the exception of auras occurring within the first 7 days after surgery. Seizure outcome was determined at annual intervals. Patients who were in Engel Class Ia at the last contact were classified as having a favorable outcome. Seizure outcome was favorable in 99 patients (71%). Six patients (4%) experienced APOS and in all cases their clinical manifestations were similar to the habitual preoperative seizures. All patients with APOS had unfavorable long-term outcome, as compared with 35 (26%) of 133 in whom APOS did not occur (p<0.001). Our study suggests that APOS, despite being relatively uncommon in patients undergoing resective surgery for TLE-HS, are associated with a worse long-term seizure outcome. Given some study limitations, our findings should be regarded as preliminary and need confirmation from future larger, prospective, multicenter studies. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  18. Efficacy and tolerability of high-dose phenobarbital in children with focal seizures.

    PubMed

    Okumura, Akihisa; Nakahara, Eri; Ikeno, Mitsuru; Abe, Shinpei; Igarashi, Ayuko; Nakazawa, Mika; Takasu, Michihiko; Shimizu, Toshiaki

    2016-04-01

    We retrospectively reviewed the outcomes of children with focal epilepsy treated with oral high-dose phenobarbital. We reviewed data on children (aged<15 years) with focal seizures treated with high-dose phenobarbital (>5 mg/kg/day to maintain a target serum level >40 μg/mL) for at least 6 months. Seizure frequency was evaluated after phenobarbital titration, and 1 and 2 years after high-dose phenobarbital treatment commenced. Treatment was judged effective when seizure frequencies fell by ⩾75%. Seven boys and eight girls were treated. The median age at commencement of high-dose phenobarbital therapy was 30 months. The maximal serum phenobarbital level ranged from 36.5 to 62.9 μg/mL. High-dose PB was effective in seven. In two patients, treatment was transiently effective, but seizure frequency later returned to the baseline. High-dose PB was ineffective in six. No significant association between effectiveness and any clinical variable was evident. Drowsiness was recorded in nine patients, but no patient developed a behavioral problem or hypersensitivity. Oral high-dose phenobarbital was effective in 7 of 15 patients with focal epilepsy and well tolerated. High-dose PB may be useful when surgical treatment is difficult. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  19. Long-term seizure outcome for international consensus classification of hippocampal sclerosis: a survival analysis.

    PubMed

    Na, Meng; Ge, Haitao; Shi, Chen; Shen, Hong; Wang, Yu; Pu, Song; Liu, Li; Wang, Haiyang; Xie, Chuncheng; Zhu, Minwei; Wang, Jiabin; Shi, Changbin; Lin, Zhiguo

    2015-02-01

    Surgery is regarded as a common treatment option for patients with mesial temporal lobe epilepsy (MTLE) as a result of hippocampal sclerosis (HS). However, approximately one-third of patients with intractable epilepsy did not become seizure-free after tailored resection strategies. It would be compelling to identify predictive factors of postoperative seizure outcomes. Our aim was to assess the correlation between HS classification and long-term postoperative seizure outcome in patients with MTLE due to HS. To investigate HS classification, semi-quantitative analysis and immunohistochemical staining of neuronal nuclei (NeuN) were performed on 100 postoperative hippocampal specimens. All patients had a 1-7 year postoperative follow-up. The postoperative seizure outcome was evaluated using International League Against Epilepsy (ILAE) outcome classification. Three types of HS were recognized. The highest incidence of initial precipitating injury (IPI) was noted in the HS ILAE type 1 group (53.1%). The most favorable long-term seizure outcome was also noted in the HS ILAE type 1 group. The shortest epilepsy duration was recorded in the HS ILAE type 2 group (mean epilepsy duration=6.64 ± 5.83 years). The completely seizure free rate of patients in all groups declined with an increase in time. Our study for the first time demonstrated a significant correlation between HS ILAE types and long-term postoperative seizure outcome in patients with MTLE due to HS. Therefore, HS ILAE types have predictive value in long-term seizure outcome following epilepsy surgery. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  20. Synchronization analysis of voltage-sensitive dye imaging during focal seizures in the rat neocortex

    NASA Astrophysics Data System (ADS)

    Takeshita, Daisuke; Bahar, Sonya

    2011-12-01

    Seizures are often assumed to result from an excess of synchronized neural activity. However, various recent studies have suggested that this is not necessarily the case. We investigate synchronization during focal neocortical seizures induced by injection of 4-aminopyridine (4AP) in the rat neocortex in vivo. Neocortical activity is monitored by field potential recording and by the fluorescence of the voltage-sensitive dye RH-1691. After removal of artifacts, the voltage-sensitive dye (VSD) signal is analyzed using the nonlinear dynamics-based technique of stochastic phase synchronization in order to determine the degree of synchronization within the neocortex during the development and spread of each seizure event. Results show a large, statistically significant increase in synchronization during seizure activity. Synchrony is typically greater between closer pixel pairs during a seizure event; the entire seizure region is synchronized almost exactly in phase. This study represents, to our knowledge, the first application of synchronization analysis methods to mammalian VSD imaging in vivo. Our observations indicate a clear increase in synchronization in this model of focal neocortical seizures across a large area of the neocortex; a sharp increase in synchronization during seizure events was observed in all 37 seizures imaged. The results are consistent with a recent computational study which simulates the effect of 4AP in a neocortical neuron model.

  1. Reduced hippocampal damage and epileptic seizures after status epilepticus in mice lacking proapoptotic Puma

    PubMed Central

    Engel, Tobias; Murphy, Brona M.; Hatazaki, Seiji; Jimenez-Mateos, Eva M.; Concannon, Caoimhin G.; Woods, Ina; Prehn, Jochen H. M.; Henshall, David C.

    2010-01-01

    The functional significance of neuronal death for pathogenesis of epilepsy and the underlying molecular mechanisms thereof remain incompletely understood. The p53 transcription factor has been implicated in seizure damage, but its target genes and the influence of cell death under its control on epilepsy development are unknown. In the present study, we report that status epilepticus (SE) triggered by intra-amygdala kainic acid in mice causes rapid p53 accumulation and subsequent hippocampal damage. Expression of p53-up-regulated mediator of apoptosis (Puma), a proapoptotic Bcl-2 homology domain 3-only protein under p53 control, was increased within a few hours of SE. Induction of Puma was blocked by pharmacologic inhibition of p53, and hippocampal damage was also reduced. Puma induction was also blocked in p53-deficient mice subject to SE. Compared to Puma-expressing mice, Puma-deficient mice had significantly smaller hippocampal lesions after SE. Long-term, continuous telemetric EEG monitoring revealed a ∼60% reduction in the frequency of epileptic seizures in the Puma-deficient mice compared to Puma-expressing mice. These are the first data showing genetic deletion of a proapoptotic protein acting acutely to influence neuronal death subsequently alters the phenotype of epilepsy in the long-term, supporting the concept that apoptotic pathway activation is a trigger of epileptogenesis.—Engel, T., Murphy, B. M., Hatazaki, S., Jimenez-Mateos, E. M., Concannon, C. G., Woods, I., Prehn, J. H. M., Henshall, D. C. Reduced hippocampal damage and epileptic seizures after status epilepticus in mice lacking proapoptotic Puma. PMID:19890018

  2. Focal Scn1a knockdown induces cognitive impairment without seizures

    PubMed Central

    Bender, Alex C.; Natola, Heather; Holmes, Gregory L.; Scott, Rod C.; Lenck-Santini, Pierre-Pascal

    2013-01-01

    Cognitive impairment is a common comorbidity in pediatric epilepsy that can severely affect quality of life. In many cases, antiepileptic treatments fail to improve cognition. Therefore, a fundamental question is whether underlying brain abnormalities may contribute to cognitive impairment through mechanisms independent of seizures. Here, we examined the possible effects on cognition of Nav1.1 down-regulation, a sodium channel principally involved in Dravet syndrome but also implicated in other cognitive disorders, including autism and Alzheimer’s disease. Using an siRNA approach to knockdown Nav1.1 selectively in the basal forebrain region, we were able to target a learning and memory network while avoiding the generation of spontaneous seizures. We show that reduction of Nav1.1 expression in the medial septum and diagonal band of Broca leads to a dysregulation of hippocampal oscillations in association with a spatial memory deficit. We propose that the underlying etiology responsible for Dravet syndrome may directly contribute to cognitive impairment in a manner that is independent from seizures. PMID:23318929

  3. Local Functional Connectivity as a Pre-Surgical Tool for Seizure Focus Identification in Non-Lesion, Focal Epilepsy

    PubMed Central

    Weaver, K. E.; Chaovalitwongse, W. A.; Novotny, E. J.; Poliakov, A.; Grabowski, T. G.; Ojemann, J. G.

    2013-01-01

    Successful resection of cortical tissue engendering seizure activity is efficacious for the treatment of refractory, focal epilepsy. The pre-operative localization of the seizure focus is therefore critical to yielding positive, post-operative outcomes. In a small proportion of focal epilepsy patients presenting with normal MRI, identification of the seizure focus is significantly more challenging. We examined the capacity of resting state functional MRI (rsfMRI) to identify the seizure focus in a group of four non-lesion, focal (NLF) epilepsy individuals. We predicted that computing patterns of local functional connectivity in and around the epileptogenic zone combined with a specific reference to the corresponding region within the contralateral hemisphere would reliably predict the location of the seizure focus. We first averaged voxel-wise regional homogeneity (ReHo) across regions of interest (ROIs) from a standardized, probabilistic atlas for each NLF subject as well as 16 age- and gender-matched controls. To examine contralateral effects, we computed a ratio of the mean pair-wise correlations of all voxels within a ROI with the corresponding contralateral region (IntraRegional Connectivity – IRC). For each subject, ROIs were ranked (from lowest to highest) on ReHo, IRC, and the mean of the two values. At the group level, we observed a significant decrease in the rank for ROI harboring the seizure focus for the ReHo rankings as well as for the mean rank. At the individual level, the seizure focus ReHo rank was within bottom 10% lowest ranked ROIs for all four NLF epilepsy patients and three out of the four for the IRC rankings. However, when the two ranks were combined (averaging across ReHo and IRC ranks and scalars), the seizure focus ROI was either the lowest or second lowest ranked ROI for three out of the four epilepsy subjects. This suggests that rsfMRI may serve as an adjunct pre-surgical tool, facilitating the identification of the seizure focus in

  4. Focal seizure associated with human parvovirus B19 infection in a non-encephalopathic child.

    PubMed

    Samanta, Debopam; Willis, Erin

    2016-02-01

    The incidence of acute symptomatic (at the time of documented brain insult) seizures and single unprovoked seizures are 29-39 and 23-61 per 100 000 per year, respectively. After stabilization of the patient, finding the etiology of the seizure is of paramount importance. A careful history and physical examination may allow a diagnosis without need for further evaluation. In the literature, severe central nervous system involvement has been reported from human parvovirus B19 infection. We reported a previously healthy 7-year-old girl who presented after an episode of focal seizure. She was afebrile and didn't have any focal neurological abnormalities. She had erythematous malar rash along with reticulating pattern of rash over her both upper extremities. Parvovirus infection was suspected due to the characteristic erythematous malar rash. Serum human parvovirus B19 DNA polymerase chain reaction was positive which was consistent with acute parvovirus infection. Further confirmation of current infection was done with Sandwich enzyme immunoassays showing positive anti-B19 IgM Index (>1.1). IgG index was equivocal (0.9-1.1). We report an extremely rare presentation of non-febrile seizure from acute parvovirus infection in a child without encephalopathy who had an excellent recovery. Timely diagnosis can provide counselling regarding future seizure recurrence risk, curtail expenditure from expensive diagnostic work up and provide additional recommendations about potential risks to a pregnant caregiver.

  5. Hippocampal closed-loop modeling and implications for seizure stimulation design.

    PubMed

    Sandler, Roman A; Song, Dong; Hampson, Robert E; Deadwyler, Sam A; Berger, Theodore W; Marmarelis, Vasilis Z

    2015-10-01

    Traditional hippocampal modeling has focused on the series of feedforward synapses known as the trisynaptic pathway. However, feedback connections from CA1 back to the hippocampus through the entorhinal cortex (EC) actually make the hippocampus a closed-loop system. By constructing a functional closed-loop model of the hippocampus, one may learn how both physiological and epileptic oscillations emerge and design efficient neurostimulation patterns to abate such oscillations. Point process input-output models where estimated from recorded rodent hippocampal data to describe the nonlinear dynamical transformation from CA3 → CA1, via the schaffer-collateral synapse, and CA1 → CA3 via the EC. Each Volterra-like subsystem was composed of linear dynamics (principal dynamic modes) followed by static nonlinearities. The two subsystems were then wired together to produce the full closed-loop model of the hippocampus. Closed-loop connectivity was found to be necessary for the emergence of theta resonances as seen in recorded data, thus validating the model. The model was then used to identify frequency parameters for the design of neurostimulation patterns to abate seizures. Deep-brain stimulation (DBS) is a new and promising therapy for intractable seizures. Currently, there is no efficient way to determine optimal frequency parameters for DBS, or even whether periodic or broadband stimuli are optimal. Data-based computational models have the potential to be used as a testbed for designing optimal DBS patterns for individual patients. However, in order for these models to be successful they must incorporate the complex closed-loop structure of the seizure focus. This study serves as a proof-of-concept of using such models to design efficient personalized DBS patterns for epilepsy.

  6. Seizure outcome after AED failure in pediatric focal epilepsy: impact of underlying etiology.

    PubMed

    Wirrell, Elaine C; Wong-Kisiel, Lily C; Nickels, Katherine C

    2014-05-01

    This study aimed to identify long-term seizure outcome in pediatric nonsyndromic focal epilepsy after failure of serial antiepileptic drugs (AEDs) due to lack of efficacy. Children (1 month-17 years) with new-onset focal epilepsy not meeting the criteria for a defined electroclinical syndrome diagnosed between 1980 and 2009 while residing in Olmsted County, MN, were retrospectively identified. Medical records of those followed for ≥2 years were reviewed to assess etiology, the number of AEDs that failed due to lack of efficacy, and seizure outcome at final follow-up. Etiology was classified into structural/metabolic, genetic, or unknown. Favorable outcome was defined as seizure freedom ≥1 year, on or off AEDs, without prior epilepsy surgery. Poor outcome was defined as ongoing seizures in the preceding year or having undergone prior epilepsy surgery. Nonsyndromic focal epilepsy accounted for 275/468 (59%) of all patients with newly diagnosed epilepsy--of these, 256 (93%) were followed for a minimum of two years and were included in the study. Median duration of follow-up was 10.0 years. At least one AED had failed due to lack of efficacy in 100 (39.1%) children. Favorable outcomes occurred in 149/156 (95.5%) children with no AED failure, 16/30 (53.3%) with one AED failure, 8/25 (32%) with two AED failures, and only 2/45 (4.4%) with three AED failures. After two AED failures, the seizures of nearly one-quarter of children who had epilepsy with an unknown cause responded favorably to the third AED compared with only 7.8% of the cohort that had epilepsy with a structural/metabolic cause. Children with a remote brain insult had a significantly higher likelihood of favorable outcome with serial AEDs than those with other structural abnormalities. Etiology is an important determinant of pharmacoresistance in nonsyndromic focal epilepsy. Surgical evaluation should be considered after failure of 1-2 AEDs in those who have epilepsy with structural causes, excluding

  7. GENE EXPRESSION CHANGES AFTER SEIZURE PRECONDITIONING IN THE THREE MAJOR HIPPOCAMPAL CELL LAYERS

    PubMed Central

    Borges, Karin; Shaw, Renee; Dingledine, Raymond

    2008-01-01

    Rodents experience hippocampal damage after status epilepticus (SE) mainly in pyramidal cells while sparing the dentate granule cell layer (DGCL). Hippocampal damage was prevented in rats that had been preconditioned by brief seizures on two consecutive days before SE. To identify neuroprotective genes and biochemical pathways changed after preconditioning we compared the effect of preconditioning on gene expression in the CA1 and CA3 pyramidal and DGCLs, harvested by laser capture microscopy. In the DGCL the expression of 632 genes was altered, compared to only 151 and 58 genes in CA1 and CA3 pyramidal cell layers. Most of the differentially expressed genes regulate tissue structure and intra- and extracellular signaling, including neurotransmission. A selective upregulation of energy metabolism transcripts occurred in CA1 pyramidal cells relative to the DGCL. These results reveal a broad transcriptional response of the DGCL to preconditioning, and suggest several mechanisms underlying the neuroprotective effect of preconditioning seizures. PMID:17239605

  8. Classification of Focal and Non Focal Epileptic Seizures Using Multi-Features and SVM Classifier.

    PubMed

    Sriraam, N; Raghu, S

    2017-09-02

    Identifying epileptogenic zones prior to surgery is an essential and crucial step in treating patients having pharmacoresistant focal epilepsy. Electroencephalogram (EEG) is a significant measurement benchmark to assess patients suffering from epilepsy. This paper investigates the application of multi-features derived from different domains to recognize the focal and non focal epileptic seizures obtained from pharmacoresistant focal epilepsy patients from Bern Barcelona database. From the dataset, five different classification tasks were formed. Total 26 features were extracted from focal and non focal EEG. Significant features were selected using Wilcoxon rank sum test by setting p-value (p < 0.05) and z-score (-1.96 > z > 1.96) at 95% significance interval. Hypothesis was made that the effect of removing outliers improves the classification accuracy. Turkey's range test was adopted for pruning outliers from feature set. Finally, 21 features were classified using optimized support vector machine (SVM) classifier with 10-fold cross validation. Bayesian optimization technique was adopted to minimize the cross-validation loss. From the simulation results, it was inferred that the highest sensitivity, specificity, and classification accuracy of 94.56%, 89.74%, and 92.15% achieved respectively and found to be better than the state-of-the-art approaches. Further, it was observed that the classification accuracy improved from 80.2% with outliers to 92.15% without outliers. The classifier performance metrics ensures the suitability of the proposed multi-features with optimized SVM classifier. It can be concluded that the proposed approach can be applied for recognition of focal EEG signals to localize epileptogenic zones.

  9. Glutamate receptor 1 phosphorylation at serine 831 and 845 modulates seizure susceptibility and hippocampal hyperexcitability after early life seizures.

    PubMed

    Rakhade, Sanjay N; Fitzgerald, Erin F; Klein, Peter M; Zhou, Chengwen; Sun, Hongyu; Huganir, Richard L; Hunganir, Richard L; Jensen, Frances E

    2012-12-05

    Neonatal seizures can lead to later life epilepsy and neurobehavioral deficits, and there are no treatments to prevent these sequelae. We showed previously that hypoxia-induced seizures in a neonatal rat model induce rapid phosphorylation of serine-831 (S831) and Serine 845 (S845) sites of the AMPA receptor GluR1 subunit and later neuronal hyperexcitability and epilepsy, suggesting that seizure-induced posttranslational modifications may represent a novel therapeutic target. To unambiguously assess the contribution of these sites, we examined seizure susceptibility in wild-type mice versus transgenic knock-in mice with deficits in GluR1 S831 and S845 phosphorylation [GluR1 double-phosphomutant (GluR1 DPM) mice]. Phosphorylation of the GluR1 S831 and S845 sites was significantly increased in the hippocampus and cortex after a single episode of pentyleneterazol-induced seizures in postnatal day 7 (P7) wild-type mouse pups and that transgenic knock-in mice have a higher threshold and longer latencies to seizures. Like the rat, hypoxic seizures in P9 C57BL/6N wild-type mice resulted in transient increases in GluR1 S831 and GluR1 S845 phosphorylation in cortex and were associated with enhanced seizure susceptibility to later-life kainic-acid-induced seizures. In contrast, later-life seizure susceptibility after hypoxia-induced seizures was attenuated in GluR1 DPM mice, supporting a role for posttranslational modifications in seizure-induced network excitability. Finally, human hippocampal samples from neonatal seizure autopsy cases also showed an increase in GluR1 S831 and S845, supporting the validation of this potential therapeutic target in human tissue.

  10. Hippocampal closed-loop modeling and implications for seizure stimulation design

    NASA Astrophysics Data System (ADS)

    Sandler, Roman A.; Song, Dong; Hampson, Robert E.; Deadwyler, Sam A.; Berger, Theodore W.; Marmarelis, Vasilis Z.

    2015-10-01

    Objective. Traditional hippocampal modeling has focused on the series of feedforward synapses known as the trisynaptic pathway. However, feedback connections from CA1 back to the hippocampus through the entorhinal cortex (EC) actually make the hippocampus a closed-loop system. By constructing a functional closed-loop model of the hippocampus, one may learn how both physiological and epileptic oscillations emerge and design efficient neurostimulation patterns to abate such oscillations. Approach. Point process input-output models where estimated from recorded rodent hippocampal data to describe the nonlinear dynamical transformation from CA3 → CA1, via the schaffer-collateral synapse, and CA1 → CA3 via the EC. Each Volterra-like subsystem was composed of linear dynamics (principal dynamic modes) followed by static nonlinearities. The two subsystems were then wired together to produce the full closed-loop model of the hippocampus. Main results. Closed-loop connectivity was found to be necessary for the emergence of theta resonances as seen in recorded data, thus validating the model. The model was then used to identify frequency parameters for the design of neurostimulation patterns to abate seizures. Significance. Deep-brain stimulation (DBS) is a new and promising therapy for intractable seizures. Currently, there is no efficient way to determine optimal frequency parameters for DBS, or even whether periodic or broadband stimuli are optimal. Data-based computational models have the potential to be used as a testbed for designing optimal DBS patterns for individual patients. However, in order for these models to be successful they must incorporate the complex closed-loop structure of the seizure focus. This study serves as a proof-of-concept of using such models to design efficient personalized DBS patterns for epilepsy.

  11. Hippocampal Closed-Loop Modeling and Implications for Seizure Stimulation Design

    PubMed Central

    Sandler, Roman A.; Song, Dong; Hampson, Robert E.; Deadwyler, Sam A.; Berger, Theodore W.; Marmarelis, Vasilis Z.

    2016-01-01

    Objective Traditional hippocampal modeling has focused on the series of feedforward synapses known as the trisynaptic pathway. However, feedback connections from CA1 back to the hippocampus through the Entorhinal Cortex (EC) actually make the hippocampus a closed-loop system. By constructing a functional closed-loop model of the hippocampus, one may learn how both physiological and epileptic oscillations emerge and design efficient neurostimulation patterns to abate such oscillations. Approach Point process input-output models where estimated from recorded rodent hippocampal data to describe the nonlinear dynamical transformation from CA3→CA1, via the Schaffer-Collateral synapse, and CA1→CA3 via the EC. Each Volterra-like subsystem was composed of linear dynamics (Principal Dynamic Modes) followed by static nonlinearities. The two subsystems were then wired together to produce the full closed-loop model of the hippocampus. Main Results Closed-loop connectivity was found to be necessary for the emergence of theta resonances as seen in recorded data, thus validating the model. The model was then used to identify frequency parameters for the design of neurostimulation patterns to abate seizures. Significance DBS is a new and promising therapy for intractable seizures. Currently, there is no efficient way to determine optimal frequency parameters for DBS, or even whether periodic or broadband stimuli are optimal. Data-based computational models have the potential to be used as a testbed for designing optimal DBS patterns for individual patients. However, in order for these models to be successful they must incorporate the complex closed-loop structure of the seizure focus. This study serves as a proof-of-concept of using such models to design efficient personalized DBS patterns for epilepsy. PMID:26355815

  12. Glutamate receptor 1 phosphorylation at Serine 831 and 845 modulates seizure susceptibility and hippocampal hyperexcitability following early life seizures

    PubMed Central

    Rakhade, S.N.; Fitzgerald, E.F.; Klein, P.M.; Zhou, C.; Sun, H; Huganir, R.L.; Jensen, F.E.

    2012-01-01

    Neonatal seizures can lead to later life epilepsy and neurobehavioral deficits, and there are no treatments to prevent these sequelae. We previously showed that hypoxia-induced seizures in a neonatal rat model induce rapid phosphorylation of S831 and S845 sites of the AMPA receptor GluR1 subunit and later neuronal hyperexcitability and epilepsy, suggesting that seizure-induced post-translational modifications may represent a novel therapeutic target. To unambiguously assess the contribution of these sites, we examined seizure susceptibility in wild type mice versus transgenic knock-in mice with deficits in GluR1 S831 and S845 phosphorylation (GluR1 double phosphomutant (GluR1DPM) mice). Phosphorylation of the GluR1 S831 and S845 sites was significantly increased in the hippocampus and cortex following a single episode of pentyleneterazol (PTZ) induced seizures in postnatal day 9 (P9) wild type mouse pups, and that transgenic knock-in mice have a higher threshold and longer latencies to seizures. Like the rat, hypoxic seizures in P9 C57BL/6N wild type mice resulted in transient increases in GluR1 S831 and GluR1 S845 phosphorylation in cortex, and were associated with enhanced seizure susceptibility to later-life kainic acid induced seizures. In contrast, later-life seizure susceptibility following hypoxia-induced seizures was attenuated in GluR1 DPM mice, supporting a role for post-translational modifications in seizure-induced network excitability. Finally, human hippocampal samples from neonatal seizure autopsy cases also showed an increase in GluR1 S831 and S845, supporting the validation of this potential therapeutic target in human tissue. PMID:23223299

  13. Seizure-like activity leads to the release of BAD from 14-3-3 protein and cell death in hippocampal neurons in vitro.

    PubMed

    Meller, R; Schindler, C K; Chu, X P; Xiong, Z G; Cameron, J A; Simon, R P; Henshall, D C

    2003-05-01

    Seizure-induced neuronal death may involve engagement of the BCL-2 family of apoptosis-regulating proteins. In the present study we examined the activation of proapoptotic BAD in cultured hippocampal neurons following seizures induced by removal of chronic glutamatergic transmission blockade. Kynurenic acid withdrawal elicited an increase in seizure-like electrical activity, which was inhibited by blockers of AMPA (CNQX) and NMDA (MK801 and AP5) receptor function. However, only NMDA receptor antagonists inhibited calcium entry as assessed by fura-2, and cell death of hippocampal neurons. Seizures increased proteolysis of caspase-3 and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) of cells. Seizure-like activity induced dephosphorylation of BAD and the disruption of its constitutive interaction with 14-3-3 proteins. In turn, BAD dimerized with antiapoptotic BCL-Xl after seizures. However, the absence of neuroprotective effects of pathway intervention suggests that BAD may perform a reinforcement rather than instigator role in cell death following seizures in vitro.

  14. Hyperventilation revisited: physiological effects and efficacy on focal seizure activation in the era of video-EEG monitoring.

    PubMed

    Guaranha, Mirian S B; Garzon, Eliana; Buchpiguel, Carlos A; Tazima, Sérgio; Yacubian, Elza M T; Sakamoto, Américo C

    2005-01-01

    Hyperventilation is an activation method that provokes physiological slowing of brain rhythms, interictal discharges, and seizures, especially in generalized idiopathic epilepsies. In this study we assessed its effectiveness in inducing focal seizures during video-EEG monitoring. We analyzed the effects of hyperventilation (HV) during video-EEG monitoring (video-EEG) of patients with medically intractable focal epilepsies. We excluded children younger than 10 years, mentally retarded patients, and individuals with frequent seizures. We analyzed 97 patients; 24 had positive seizure activation (PSA), and 73 had negative seizure activation (NSA). No differences were found between groups regarding sex, age, age at epilepsy onset, duration of epilepsy, frequency of seizures, and etiology. Temporal lobe epilepsies were significantly more activated than frontal lobe epilepsies. Spontaneous and activated seizures did not differ in terms of their clinical characteristics, and the activation did not affect the performance of ictal single-photon emission computed tomography (SPECT). HV is a safe and effective method of seizure activation during monitoring. It does not modify any of the characteristics of the seizures and allows the obtaining of valuable ictal SPECTs. This observation is clinically relevant and suggests the effectiveness and the potential of HV in shortening the presurgical evaluation, especially of temporal lobe epilepsy patients, consequently reducing its costs and increasing the number of candidates for epilepsy surgery.

  15. Frequent Seizures Are Associated with a Network of Gray Matter Atrophy in Temporal Lobe Epilepsy with or without Hippocampal Sclerosis

    PubMed Central

    Coan, Ana C.; Campos, Brunno M.; Yasuda, Clarissa L.; Kubota, Bruno Y.; Bergo, Felipe PG.; Guerreiro, Carlos AM.; Cendes, Fernando

    2014-01-01

    Objective Patients with temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS) have diffuse subtle gray matter (GM) atrophy detectable by MRI quantification analyses. However, it is not clear whether the etiology and seizure frequency are associated with this atrophy. We aimed to evaluate the occurrence of GM atrophy and the influence of seizure frequency in patients with TLE and either normal MRI (TLE-NL) or MRI signs of HS (TLE-HS). Methods We evaluated a group of 172 consecutive patients with unilateral TLE-HS or TLE-NL as defined by hippocampal volumetry and signal quantification (122 TLE-HS and 50 TLE-NL) plus a group of 82 healthy individuals. Voxel-based morphometry was performed with VBM8/SPM8 in 3T MRIs. Patients with up to three complex partial seizures and no generalized tonic-clonic seizures in the previous year were considered to have infrequent seizures. Those who did not fulfill these criteria were considered to have frequent seizures. Results Patients with TLE-HS had more pronounced GM atrophy, including the ipsilateral mesial temporal structures, temporal lobe, bilateral thalami and pre/post-central gyri. Patients with TLE-NL had more subtle GM atrophy, including the ipsilateral orbitofrontal cortex, bilateral thalami and pre/post-central gyri. Both TLE-HS and TLE-NL showed increased GM volume in the contralateral pons. TLE-HS patients with frequent seizures had more pronounced GM atrophy in extra-temporal regions than TLE-HS with infrequent seizures. Patients with TLE-NL and infrequent seizures had no detectable GM atrophy. In both TLE-HS and TLE-NL, the duration of epilepsy correlated with GM atrophy in extra-hippocampal regions. Conclusion Although a diffuse network GM atrophy occurs in both TLE-HS and TLE-NL, this is strikingly more evident in TLE-HS and in patients with frequent seizures. These findings suggest that neocortical atrophy in TLE is related to the ongoing seizures and epilepsy duration, while thalamic atrophy is more

  16. Age-dependent long-term structural and functional effects of early life seizures: evidence for a hippocampal critical period influencing plasticity in adulthood

    PubMed Central

    Meyerand, M.E.; Sutula, T.

    2015-01-01

    Neural activity promotes circuit formation in developing systems and during critical periods permanently modifies circuit organization and functional properties. These observations suggest that excessive neural activity, as occurs during seizures, might influence developing neural circuitry with long-term outcomes that depend on age at the time of seizures. We systematically examined long-term structural and functional consequences of seizures induced in rats by kainic acid, pentylenetetrazol, and hyperthermia across postnatal ages from birth through postnatal day 90 in adulthood (P90). Magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and electrophysiological methods at ≥P95 following seizures induced from P1 to P90 demonstrated consistent patterns of gross atrophy, microstructural abnormalities in the corpus callosum and hippocampus, and functional alterations in hippocampal circuitry at ≥P95 that were independent of the method of seizure induction and varied systematically as a function of age at the time of seizures. Three distinct epochs were observed in which seizures resulted in distinct long-term structural and functional outcomes at ≥P95. Seizures prior to P20 resulted in DTI abnormalities in corpus callosum and hippocampus in the absence of gross cerebral atrophy, and increased paired pulse inhibition (PPI) in the dentate gyrus at ≥P95. Seizures after P30 induced a different pattern of DTI abnormalities in the fimbria and hippocampus accompanied by gross cerebral atrophy with increases in lateral ventricular volume, as well as increased PPI in the dentate gyrus at ≥P95. In contrast, seizures between P20-P30 did not result in cerebral atrophy or significant imaging abnormalities in the hippocampus or white matter, but irreversibly decreased PPI in the dentate gyrus compared to normal adult controls. These age-specific long-term structural and functional outcomes identify P20-P30 as a potential critical period in hippocampal

  17. The phenotypic spectrum of ARHGEF9 includes intellectual disability, focal epilepsy and febrile seizures.

    PubMed

    Klein, Karl Martin; Pendziwiat, Manuela; Eilam, Anda; Gilad, Ronit; Blatt, Ilan; Rosenow, Felix; Kanaan, Moien; Helbig, Ingo; Afawi, Zaid

    2017-07-01

    Mutations or structural genomic alterations of the X-chromosomal gene ARHGEF9 have been described in male and female patients with intellectual disability. Hyperekplexia and epilepsy were observed to a variable degree, but incompletely described. Here, we expand the phenotypic spectrum of ARHGEF9 by describing a large Ethiopian-Jewish family with epilepsy and intellectual disability. The four affected male siblings, their unaffected parents and two unaffected female siblings were recruited and phenotyped. Parametric linkage analysis was performed using SNP microarrays. Variants from exome sequencing in two affected individuals were confirmed by Sanger sequencing. All affected male siblings had febrile seizures from age 2-3 years and intellectual disability. Three developed afebrile seizures between age 7-17 years. Three showed focal seizure semiology. None had hyperekplexia. A novel ARHGEF9 variant (c.967G>A, p.G323R, NM_015185.2) was hemizygous in all affected male siblings and heterozygous in the mother. This family reveals that the phenotypic spectrum of ARHGEF9 is broader than commonly assumed and includes febrile seizures and focal epilepsy with intellectual disability in the absence of hyperekplexia or other clinically distinguishing features. Our findings suggest that pathogenic variants in ARHGEF9 may be more common than previously assumed in patients with intellectual disability and mild epilepsy.

  18. Lacosamide: A Review in Focal-Onset Seizures in Patients with Epilepsy.

    PubMed

    Hoy, Sheridan M

    2018-05-01

    Lacosamide (Vimpat ® ) is a functionalized amino acid (available orally and intravenously) approved in the EU and the USA for use as monotherapy and adjunctive therapy for the treatment of focal-onset seizures in adults, adolescents and children aged ≥ 4 years with epilepsy. In adults and adolescents (aged ≥ 16 years), oral lacosamide as adjunctive therapy to other antiepileptic drugs was generally effective in reducing seizure frequency during short-term (up to 18 weeks) treatment, with efficacy sustained over the longer-term (up to 8 years). Moreover, patients were effectively switched from adjunctive oral lacosamide to the same dosage of intravenous lacosamide. Oral lacosamide was an effective conversion to monotherapy agent in this patient population and as monotherapy demonstrated noninferiority to carbamazepine controlled release in terms of seizure freedom. Antiepileptic benefits were maintained during longer-term (≤ 2 years) monotherapy. The antiepileptic efficacy of lacosamide in children aged ≥ 4 years has been extrapolated from data from adults and adolescents, with a similar response expected provided paediatric dosage adaptations are used and safety is demonstrated. Indeed, preliminary data demonstrated the efficacy of short-term (16 weeks) adjunctive lacosamide in patients aged ≥ 4 to < 17 years. Oral lacosamide was generally well tolerated over the short- and longer-term when administered as adjunctive therapy, a conversion to monotherapy agent and monotherapy in adults and adolescents and when administered as adjunctive therapy in children aged ≥ 4 years. Thus, lacosamide is a useful option for the management of focal-onset seizures across a broad age range, starting as early as 4 years of age.

  19. Anti-Neuronal Autoantibodies in Both Drug Responsive and Resistant Focal Seizures with Unknown Cause.

    PubMed

    Gozubatik-Celik, Gokcen; Ozkara, Cigdem; Ulusoy, Canan; Gunduz, Aysegul; Delil, Sakir; Yeni, Naz; Tuzun, Erdem

    2017-09-01

    and Objective Autoimmunity is an emerging field of research in the etiology of different neurological disorders including epilepsy. We aimed to investigate the presence of neuronal autoantibodies in focal epilepsy with unknown cause and their clinical correlates in both drug-responsive and resistant patients. Between 2009 and 2010 94 patients were prospectively enrolled, had their antibodies tested and clinically followed." An additional 50 age- and gender-matched controls were also tested for antibodies. Age at examination, gender, age at onset, seizure frequency, risk factors, seizure precipitants, and type of seizures were noted. Plasma obtained from patients was frozen at -80°C and analysed for autoantibodies against VGKC-complex, VGCC, GAD, LGI1, CASPR2, NMDA, AMPA and GABAB receptors with immunocytochemistry and radioimmunoassay as required. Thirteen (13.8%) patients, but none of the controls, had antibodies (p=0.003). Antibodies were directed against the uncharacterized components of VGKC-complex in 5 patients (5.3%), GAD in 4 patients (4.2%), NMDA-R in 1 patient (1%), AMPA-R in 1 patient (1%) and both GAD and VGKC-complex in 2 patients (2.1%). Prognosis of epilepsy, in subsequent follow-up, did not correlate to general presence of anti-neuronal antibodies with slightly more patients with antibodies epilepsy control than without (76.9% vs. 69.1%, not-statistically significant. Three patients with suspected active autoimmunity and epilepsy who were treated, showed a response to treatment with a reduction in the seizure frequency. Although most clinical features were identical between seropositive and seronegative patient groups, seropositive patients were more likely to have inflammatory/autoimmune disorders in their medical history. In keeping with previous studies, we have shown anti-neuronal antibodies in a proportion of focal epilepsy patients. Although autoimmunity might merely occur as a bystander effect in many chronic neurological disorders

  20. Adjunctive lacosamide for focal epilepsy: an open-label trial evaluating the impact of flexible titration and dosing on safety and seizure outcomes.

    PubMed

    Baulac, Michel; Coulbaut, Safia; Doty, Pamela; McShea, Cindy; De Backer, Marc; Bartolomei, Fabrice; Vlaicu, Mihaela

    2017-06-01

    To evaluate the safety and effectiveness of lacosamide in a real-life setting with the use of a flexible dose titration schedule and individualised maintenance doses up to the maximum approved dose of 400 mg/day. Adults with a diagnosis of focal seizures, with or without secondary generalization, were enrolled in this open-label Phase IV trial (NCT01235403). Lacosamide was initiated at 100 mg/day (50 mg bid) and uptitrated over a 12-week period to 200, 300 or 400 mg/day, based on safety and seizure control. Although dose increases were to be in increments of 100 mg/day, intermediate doses were permitted at each escalation step for one week for patients known to be particularly sensitive to starting new AEDs. After receiving a stable, effective dose for three weeks, patients entered the 12-week maintenance period. Primary outcomes were incidence of treatment-emergent adverse events (TEAEs) and withdrawal due to TEAEs. Seizure outcomes, all secondary, were median focal seizure frequency, ≥50% reduction in focal seizure frequency, and seizure freedom. One hundred patients with a mean age of 44 years were enrolled and 74 completed the trial. The incidence of TEAEs was 64.0% (n=100), with the most frequently reported (≥5% of patients) being dizziness, headache, and asthenia. Fourteen patients withdrew due to TEAEs, most frequently due to dizziness (six patients; 6.0%), vomiting (two patients; 2%), and tremor (two patients; 2%). Among patients with baseline and maintenance phase seizure data (n=75), median reduction in focal seizure frequency from baseline was 69.7% and the ≥50% responder rate was 69.3%. Among 74 patients who completed the maintenance phase, 21 (28.4%) were seizure-free. Flexible lacosamide dosing in this open-label trial was associated with a favourable tolerability and safety profile; the nature of the TEAEs was consistent with that observed in previous pivotal trials. Treatment with lacosamide was also associated with effective seizure

  1. Enhanced oscillatory activity in the hippocampal-prefrontal network is related to short-term memory function after early-life seizures

    PubMed Central

    Kleen, Jonathan K.; Wu, Edie X.; Holmes, Gregory L.; Scott, Rod C.; Lenck-Santini, Pierre-Pascal

    2011-01-01

    Neurological insults during development are associated with later impairments in learning and memory. Although remedial training can help restore cognitive function, the neural mechanisms of this recovery in memory systems are largely unknown. To examine this issue we measured electrophysiological oscillatory activity in the hippocampus (both CA3 and CA1) and prefrontal cortex of adult rats that had experienced repeated seizures in the first weeks of life, while they were remedially trained on a delayed-nonmatch-to-sample memory task. Seizure-exposed rats showed initial difficulties learning the task but performed similar to control rats after extra training. Whole-session analyses illustrated enhanced theta power in all three structures while seizure rats learned response tasks prior to the memory task. Whilst performing the memory task, dynamic oscillation patterns revealed that prefrontal cortex theta power was increased among seizure-exposed rats. This enhancement appeared after the first memory training steps using short delays and plateaued at the most difficult steps which included both short and long delays. Further, seizure rats showed enhanced CA1-prefrontal theta coherence in correct trials compared to incorrect trials when long delays were imposed, suggesting increased hippocampal-prefrontal synchrony for the task in this group when memory demand was high. Seizure-exposed rats also showed heightened gamma power and coherence among all three structures during the trials. Our results demonstrate the first evidence of hippocampal-prefrontal enhancements following seizures in early development. Dynamic compensatory changes in this network and interconnected circuits may underpin cognitive rehabilitation following other neurological insults to higher cognitive systems. PMID:22031886

  2. Electric field strength and focality in electroconvulsive therapy and magnetic seizure therapy: a finite element simulation study

    NASA Astrophysics Data System (ADS)

    Deng, Zhi-De; Lisanby, Sarah H.; Peterchev, Angel V.

    2011-02-01

    We present the first computational study comparing the electric field induced by various electroconvulsive therapy (ECT) and magnetic seizure therapy (MST) paradigms. Four ECT electrode configurations (bilateral, bifrontal, right unilateral, and focal electrically administered seizure therapy) and three MST coil configurations (circular, cap, and double cone) were modeled. The model incorporated a modality-specific neural activation threshold. ECT (0.3 ms pulse width) and MST induced the maximum electric field of 2.1-2.5 V cm-1 and 1.1-2.2 V cm-1 in the brain, corresponding to 6.2-7.2 times and 1.2-2.3 times the neural activation threshold, respectively. The MST electric field is more confined to the superficial cortex compared to ECT. The brain volume stimulated was much larger with ECT (up to 100%) than with MST (up to 8.2%). MST with the double-cone coil was the most focal, and bilateral ECT was the least focal. Our results suggest a possible biophysical explanation of the reduced side effects of MST compared to ECT. Our results also indicate that the conventional ECT pulse amplitude (800-900 mA) is much higher than necessary for seizure induction. Reducing the ECT pulse amplitude should be explored as a potential means of diminishing side effects.

  3. Electric field strength and focality in electroconvulsive therapy and magnetic seizure therapy: A finite element simulation study

    PubMed Central

    Deng, Zhi-De; Lisanby, Sarah H.; Peterchev, Angel V.

    2014-01-01

    We present the first computational study comparing the electric field induced by various electroconvulsive therapy (ECT) and magnetic seizure therapy (MST) paradigms. Four ECT electrode configurations (bilateral, bifrontal, right unilateral, and focal electrically administered seizure therapy) and three MST coil configurations (circular, cap, and double cone) were modeled. The model incorporated a modality-specific neural activation threshold. ECT (0.3 ms pulse width) and MST induced maximum electric field in the brain of 2.1–2.5 V/cm and 1.1–2.2 V/cm, corresponding to 6.2–7.2 times and 1.2–2.3 times the neural activation threshold, respectively. The MST electric field is more confined to the superficial cortex compared to ECT. The brain volume stimulated was much higher with ECT (up to 100%) than MST (up to 8.2%). MST with the double cone coil was the most focal and bilateral ECT was the least focal. Our results suggest a possible biophysical explanation of the reduced side effects of MST compared to ECT. Our results also indicate that the conventional ECT pulse amplitude (800–900 mA) is much higher than necessary for seizure induction. Reducing the ECT pulse amplitude should be explored as a potential means of diminishing side effects. PMID:21248385

  4. Hippocampal Expression of Connexin36 and Connexin43 during Epileptogenesis in Pilocarpine Model of Epilepsy

    PubMed Central

    Motaghi, Sahel; Sayyah, Mohammad; Babapour, Vahab; Mahdian, Reza

    2017-01-01

    Background: Gap junctions (GJs) provide direct intercellular communications that are formed by hexameric protein subunits, called connexin (Cx). The role of Cxs in epileptogenesis has not received sufficient attention. Hippocampus with a critical function in epileptogenesis has a wide network of GJs. We examined the protein expression levels of hippocampal Cx36 (the prominent Cx present between GABAergic interneurons) and Cx43 (the main Cx expressed by astrocytes) during epileptogenesis in the pilocarpine model of epilepsy. Methods: Male Wistar rats received scopolamine (1 mg/kg, s.c.). Pilocarpine (380 mg/kg, i.p.) was administered 30 min thereafter to induce status epilepticus (SE). SE was stopped 2 h later by diazepam (10 mg/kg, i.p.). Cx36 and Cx43 protein expression was assessed by Western blot analysis in the hippocampus of SE-experienced rats, after injection of diazepam (F0 subgroup), after acquisition of focal seizures (F3 subgroup), and after development of generalized seizures (F5 subgroup). The control subgroups, C0, C3, and C5, were aged-matched rats, which received saline (1 ml/kg, i.p.) instead of pilocarpine. Injection of scopolamine and diazepam, and dissection of hippocampi were carried out at the same time interval as the test subgroups. Results: SE emerged in 67.1% of pilocarpine-treated animals. Focal and generalized seizures developed 3.8±0.4 and 7.0±0.5 days after SE, respectively. Cx36 protein abundance was not significantly different between test and control groups in the three time points. However, Cx43 protein level showed 40% increase in F3 subgroup (P<0.05 compared to C3, P<0.01 compared to F0 and F5). Conclusion: Hippocampal Cx43 is overexpressed in pilocarpine model of epileptogenesis after acquisition of focal seizures. PMID:28042145

  5. Surgical pathology of epilepsy-associated non-neoplastic cerebral lesions: a brief introduction with special reference to hippocampal sclerosis and focal cortical dysplasia

    PubMed Central

    Miyata, Hajime; Hori, Tomokatsu; Vinters, Harry V.

    2014-01-01

    Among epilepsy-associated non-neoplastic lesions, mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS) and malformation of cortical development (MCD) including focal cortical dysplasia (FCD), are the two most frequent causes of drug-resistant focal epilepsies constituting about 50% of all surgical pathology of epilepsy. Several distinct histological patterns have been historically recognized in both HS and FCD, and several studies have tried to perform clinicopathological correlation; results, however, have been controversial, particularly in terms of postsurgical seizure outcome. Recently, the International League Against Epilepsy constituted a Task Forces of Neuropathology and FCD within the Commission on Diagnostic Methods, to establish an international consensus of histological classification of HS and FCD, respectively, based on agreement with the recognition of the importance of defining a histopathological classification system that reliably has some clinicopathological correlation. Such consensus classifications are likely to facilitate future clinicopathological study. Meanwhile, we reviewed neuropathology of 41 surgical cases of mTLE, and confirmed three type/patterns of HS along with no HS, based on the qualitative evaluation of the distribution and severity of neuronal loss and gliosis within hippocampal formation; i.e., HS type 1 (61%) equivalent to ‘classical’ Ammon’s horn sclerosis, HS type 2 (2%) representing CA1 sclerosis, HS type 3 (17%) equivalent to end folium sclerosis, and no HS (19%). Furthermore we performed a neuropathological comparative study on mTLE-HS and dementia associated HS (d-HS) in elderly, and confirmed that neuropathological features differ between mTLE-HS and d-HS in the distribution of hippocampal neuronal loss and gliosis, morphology of reactive astrocytes and their protein expression, and presence of concomitant neurodegenerative changes particularly Alzheimer type and TDP-43 pathologies. These

  6. Transsylvian selective amygdalohippocampectomy in children with hippocampal sclerosis: seizure, intellectual and memory outcome.

    PubMed

    Beaton, Anne E; Durnford, Andrew; Heffer-Rahn, Phillip E; Kirkham, Fenella; Griffin, Angela; Gray, William P; Gray, W L S

    2012-11-01

    This study investigates the efficacy of transylvian selective amygdalohippocampectomy (TS SAH) in children with medically intractable epilepsy due to unilateral hippocampal sclerosis. Post-surgical seizure control, intellectual and memory outcomes are examined. This study reports on pre- and post-surgical clinical data from 10 patients who underwent TS SAH between 2002 and 2010 after 24 months follow-up. Pre- and post-operative change in seizure frequency, AED use, intellect and memory are compared. At 12 months and 24 months post-surgery, 9/10 (90%) and 7/8 (87.5%) patients respectively, were seizure free (Engel I). No patients were classed as Engel III or IV. No significant improvement or decline at a group level was found on measures of intellect or verbal or visual memory. One hundred per cent improved or remained within 1 SD of their pre-operatives score on verbal and perceptual reasoning learning and reasoning measures. Significant improvement was found post-operatively for both immediate and delayed facial memory. Our findings of good post-surgical seizure control and favourable cognitive outcome provides evidence against previous findings that SAH in children may not be effective. Copyright © 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  7. VEGF Receptor-2 (Flk-1) Overexpression in Mice Counteracts Focal Epileptic Seizures

    PubMed Central

    Nikitidou, Litsa; Kanter-Schlifke, Irene; Dhondt, Joke; Carmeliet, Peter; Lambrechts, Diether; Kokaia, Mérab

    2012-01-01

    Vascular endothelial growth factor (VEGF) was first described as an angiogenic agent, but has recently also been shown to exert various neurotrophic and neuroprotective effects in the nervous system. These effects of VEGF are mainly mediated by its receptor, VEGFR-2, which is also referred to as the fetal liver kinase receptor 1 (Flk-1). VEGF is up-regulated in neurons and glial cells after epileptic seizures and counteracts seizure-induced neurodegeneration. In vitro, VEGF administration suppresses ictal and interictal epileptiform activity caused by AP4 and 0 Mg2+ via Flk-1 receptor. We therefore explored whether increased VEGF signaling through Flk-1 overexpression may regulate epileptogenesis and ictogenesis in vivo. To this extent, we used transgenic mice overexpressing Flk-1 postnatally in neurons. Intriguingly, Flk-1 overexpressing mice were characterized by an elevated threshold for seizure induction and a decreased duration of focal afterdischarges, indicating anti-ictal action. On the other hand, the kindling progression in these mice was similar to wild-type controls. No significant effects on blood vessels or glia cells, as assessed by Glut1 and GFAP immunohistochemistry, were detected. These results suggest that increased VEGF signaling via overexpression of Flk-1 receptors may directly affect seizure activity even without altering angiogenesis. Thus, Flk-1 could be considered as a novel target for developing future gene therapy strategies against ictal epileptic activity. PMID:22808185

  8. Hypoxia-Induced neonatal seizures diminish silent synapses and long-term potentiation in hippocampal CA1 neurons

    PubMed Central

    Zhou, Chengwen; Bell, Jocelyn J. Lippman; Sun, Hongyu; Jensen, Frances E.

    2012-01-01

    Neonatal seizures can lead to epilepsy and long-term cognitive deficits in adulthood. Using a rodent model of the most common form of human neonatal seizures, hypoxia-induced seizures (HS), we aimed to determine whether these seizures modify long-term potentiation (LTP) and “silent” N-methyl-D-aspartate receptor (NMDAR)-only synapses in hippocampal CA1. At 48-72 hours (hrs) post-HS, electrophysiology and immunofluorescent confocal microscopy revealed a significant decrease in the incidence of silent synapses, and an increase in amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) at the synapses. Coincident with this decrease in silent synapses, there was an attenuation of LTP elicited by either tetanic stimulation of Schaffer collaterals or a pairing protocol, and persistent attenuation of LTP in slices removed in later adulthood after P10 HS. Furthermore, post-seizure treatment in vivo with the AMPAR antagonist 2,3-dihydroxy-6-nitro-7-sulfonyl-benzo[f]quinoxaline (NBQX) protected against the HS-induced depletion of silent synapses and preserved LTP. Thus, this study demonstrates a novel mechanism by which early-life seizures could impair synaptic plasticity, suggesting a potential target for therapeutic strategies to prevent long-term cognitive deficits. PMID:22171027

  9. Menstrual cycle worsening of epileptic seizures in women with symptomatic focal epilepsy.

    PubMed

    Bazán, Ana Carolina Belini; Montenegro, Maria Augusta; Cendes, Fernando; Min, Li Li; Guerreiro, Carlos A M

    2005-09-01

    Hormonal fluctuation is responsible for worsening of epileptic seizures during the menstrual cycle. To identify irregularities in the menstrual cycles of women with mesial temporal lobe epilepsy (MTLE) and extratemporal focal epilepsy (ETFE) and correlate the frequency of seizures during the menstrual cycles. We evaluated prospectively women in the menacme with MTLE and ETFE. Calendars were provided for these patients, and they were asked to mark their seizure frequency according to the menses. Calendars were reviewed in each routine medical appointment. Thirty-nine patients with MTLE and 14 with ETFE were evaluated. We registered 211 cycles in the patients with MTLE and 49 in those with ETFE. Irregular menstrual cycles were found in 28 (28/39, 71.7%) patients with MTLE and 6 (6/14, 42.8%) with ETFE (p=0.052). Premenstrual seizure worsening was observed in 46 (21.8%) patients with MTLE and 9 (18.3%) with ETFE (p=0.596). Menstrual worsening was observed in 47 (22.2%) patients with MTLE and 15 (30.6%) with ETFE (p=0.217). Ovulatory worsening was observed in 36 (17%) patients with MTLE and 13 (26.5%) with ETFE (p=0,126). Catamenial worsening was observed in 58 (27.4%) of the patients with MTLE and in 17 (34.7%) of the patients with ETFE (p=0.315). There was no difference between the group of patients with MTLE and ETFE regarding the frequency of irregular cycles and seizure worsening during the premenstrual, menstrual, catamenial or ovulatory periods.

  10. Hippocampal effective synchronization values are not pre-seizure indicator without considering the state of the onset channels

    PubMed Central

    Shayegh, Farzaneh; Sadri, Saeed; Amirfattahi, Rassoul; Ansari-Asl, Karim; Bellanger, Jean-Jacques; Senhadji, Lotfi

    2014-01-01

    In this paper, a model-based approach is presented to quantify the effective synchrony between hippocampal areas from depth-EEG signals. This approach is based on the parameter identification procedure of a realistic Multi-Source/Multi-Channel (MSMC) hippocampal model that simulates the function of different areas of hippocampus. In the model it is supposed that the observed signals recorded using intracranial electrodes are generated by some hidden neuronal sources, according to some parameters. An algorithm is proposed to extract the intrinsic (solely relative to one hippocampal area) and extrinsic (coupling coefficients between two areas) model parameters, simultaneously, by a Maximum Likelihood (ML) method. Coupling coefficients are considered as the measure of effective synchronization. This work can be considered as an application of Dynamic Causal Modeling (DCM) that enables us to understand effective synchronization changes during transition from inter-ictal to pre -ictal state. The algorithm is first validated by using some synthetic datasets. Then by extracting the coupling coefficients of real depth-EEG signals by the proposed approach, it is observed that the coupling values show no significant difference between ictal, pre-ictal and inter-ictal states, i.e., either the increase or decrease of coupling coefficients has been observed in all states. However, taking the value of intrinsic parameters into account, pre-seizure state can be distinguished from inter-ictal state. It is claimed that seizures start to appear when there are seizure-related physiological parameters on the onset channel, and its coupling coefficient toward other channels increases simultaneously. As a result of considering both intrinsic and extrinsic parameters as the feature vector, inter-ictal, pre-ictal and ictal activities are discriminated from each other with an accuracy of 91.33% accuracy. PMID:25061815

  11. Clinical characteristics in focal cortical dysplasia: a retrospective evaluation in a series of 120 patients.

    PubMed

    Fauser, Susanne; Huppertz, Hans-Juergen; Bast, Thomas; Strobl, Karl; Pantazis, Georgios; Altenmueller, Dirk-Matthias; Feil, Bertram; Rona, Sabine; Kurth, Christoph; Rating, Dietz; Korinthenberg, Rudolf; Steinhoff, Bernhard J; Volk, Benedikt; Schulze-Bonhage, Andreas

    2006-07-01

    Focal cortical dysplasias (FCDs) are increasingly diagnosed as a cause of symptomatic focal epilepsy in paediatric and adult patients. However, little is known about the clinical characteristics of epilepsy in these patients. In order to elucidate the clinical characteristics of their epilepsy, 120 pharmacoresistant patients including children and adults with histologically proven FCD were studied retrospectively. Age at seizure onset was analysed in the total group and compared between subgroups with different localization and different histological subtypes of FCD. The role of febrile seizures with respect to dual pathology was investigated. Seizure semiology was analysed focusing on initial seizure type and change of seizure semiology during the course of disease. Finally, transient responsiveness to antiepileptic drug therapy was studied. In the majority of patients, epilepsy began in the first 5 years of life. However, onset of epilepsy could also occur in the second or third decade until the age of 60. Age at epilepsy onset was not significantly different between temporal, extratemporal and multilobar localization of FCD. Patients without cytoarchitectural abnormalities (mild malformations of cortical development, FCD 1a according to Palmini) had significantly later epilepsy onset (P= 0.001) compared with patients with cytoarchitectural abnormalities (FCD 1b, 2a and 2b according to Palmini). In patients with additional hippocampal sclerosis (dual pathology) febrile seizures were significantly more frequently reported (P = 0.02) than in patients without dual pathology. Moreover, patients with dual pathology and febrile seizures significantly more frequently presented with severe hippocampal sclerosis (Wyler Grade 3-4) as compared with patients with dual pathology in the absence of febrile seizures (P = 0.03). First observed seizures were mainly tonic or generalized tonic-clonic. A change of seizure semiology seemed to be age-dependent and occurred between the

  12. Genital automatisms: Reappraisal of a remarkable but ignored symptom of focal seizures.

    PubMed

    Dede, Hava Özlem; Bebek, Nerses; Gürses, Candan; Baysal-Kıraç, Leyla; Baykan, Betül; Gökyiğit, Ayşen

    2018-03-01

    Genital automatisms (GAs) are uncommon clinical phenomena of focal seizures. They are defined as repeated fondling, grabbing, or scratching of the genitals. The aim of this study was to determine the lateralizing and localizing value and associated clinical characteristics of GAs. Three hundred thirteen consecutive patients with drug-resistant seizures who were referred to our tertiary center for presurgical evaluation between 2009 and 2016 were investigated. The incidence of specific kinds of behavior, clinical semiology, associated symptoms/signs with corresponding ictal electroencephalography (EEG) findings, and their potential role in seizure localization and lateralization were evaluated. Fifteen (4.8%) of 313 patients had GAs. Genital automatisms were identified in 19 (16.4%) of a total 116 seizures. Genital automatisms were observed to occur more often in men than in women (M/F: 10/5). Nine of fifteen patients (60%) had temporal lobe epilepsy (right/left: 4/5) and three (20%) had frontal lobe epilepsy (right/left: 1/2), whereas the remaining two patients could not be classified. One patient was diagnosed as having Rasmussen encephalitis. Genital automatisms were ipsilateral to epileptic focus in 12 patients and contralateral in only one patient according to ictal-interictal EEG and neuroimaging findings. Epileptic focus could not be lateralized in the last 2 patients. Genital automatisms were associated with unilateral hand automatisms such as postictal nose wiping or manual automatisms in 13 (86.7%) of 15 and contralateral dystonia was seen in 6 patients. All patients had amnesia of the performance of GAs. Genital automatisms are more frequent in seizures originating from the temporal lobe, and they can also be seen in frontal lobe seizures. Genital automatisms seem to have a high lateralizing value to the ipsilateral hemisphere and are mostly concordant with other unilateral hand automatisms. Men exhibit GAs more often than women. Copyright © 2017

  13. Toward a noninvasive automatic seizure control system in rats with transcranial focal stimulations via tripolar concentric ring electrodes

    PubMed Central

    Makeyev, Oleksandr; Liu, Xiang; Luna-Munguía, Hiram; Rogel-Salazar, Gabriela; Mucio-Ramirez, Samuel; Liu, Yuhong; Sun, Yan L.; Kay, Steven M.; Besio, Walter G.

    2012-01-01

    Epilepsy affects approximately one percent of the world population. Antiepileptic drugs are ineffective in approximately 30% of patients and have side effects. We are developing a noninvasive, or minimally invasive, transcranial focal electrical stimulation system through our novel tripolar concentric ring electrodes to control seizures. In this study we demonstrate feasibility of an automatic seizure control system in rats with pentylenetetrazole-induced seizures through single and multiple stimulations. These stimulations are automatically triggered by a real-time electrographic seizure activity detector based on a disjunctive combination of detections from a cumulative sum algorithm and a generalized likelihood ratio test. An average seizure onset detection accuracy of 76.14% was obtained for the test set (n = 13). Detection of electrographic seizure activity was accomplished in advance of the early behavioral seizure activity in 76.92% of the cases. Automatically triggered stimulation significantly (p = 0.001) reduced the electrographic seizure activity power in the once stimulated group compared to controls in 70% of the cases. To the best of our knowledge this is the first closed-loop automatic seizure control system based on noninvasive electrical brain stimulation using tripolar concentric ring electrode electrographic seizure activity as feedback. PMID:22772373

  14. Toward a noninvasive automatic seizure control system in rats with transcranial focal stimulations via tripolar concentric ring electrodes.

    PubMed

    Makeyev, Oleksandr; Liu, Xiang; Luna-Munguía, Hiram; Rogel-Salazar, Gabriela; Mucio-Ramirez, Samuel; Liu, Yuhong; Sun, Yan L; Kay, Steven M; Besio, Walter G

    2012-07-01

    Epilepsy affects approximately 1% of the world population. Antiepileptic drugs are ineffective in approximately 30% of patients and have side effects. We are developing a noninvasive, or minimally invasive, transcranial focal electrical stimulation system through our novel tripolar concentric ring electrodes to control seizures. In this study, we demonstrate feasibility of an automatic seizure control system in rats with pentylenetetrazole-induced seizures through single and multiple stimulations. These stimulations are automatically triggered by a real-time electrographic seizure activity detector based on a disjunctive combination of detections from a cumulative sum algorithm and a generalized likelihood ratio test. An average seizure onset detection accuracy of 76.14% was obtained for the test set (n = 13). Detection of electrographic seizure activity was accomplished in advance of the early behavioral seizure activity in 76.92% of the cases. Automatically triggered stimulation significantly (p = 0.001) reduced the electrographic seizure activity power in the once stimulated group compared to controls in 70% of the cases. To the best of our knowledge this is the first closed-loop automatic seizure control system based on noninvasive electrical brain stimulation using tripolar concentric ring electrode electrographic seizure activity as feedback.

  15. Unit Activity of Hippocampal Interneurons before Spontaneous Seizures in an Animal Model of Temporal Lobe Epilepsy

    PubMed Central

    Toyoda, Izumi; Fujita, Satoshi; Thamattoor, Ajoy K.

    2015-01-01

    Mechanisms of seizure initiation are unclear. To evaluate the possible roles of inhibitory neurons, unit recordings were obtained in the dentate gyrus, CA3, CA1, and subiculum of epileptic pilocarpine-treated rats as they experienced spontaneous seizures. Most interneurons in the dentate gyrus, CA1, and subiculum increased their firing rate before seizures, and did so with significant consistency from seizure to seizure. Identification of CA1 interneuron subtypes based on firing characteristics during theta and sharp waves suggested that a parvalbumin-positive basket cell and putative bistratified cells, but not oriens lacunosum moleculare cells, were activated preictally. Preictal changes occurred much earlier than those described by most previous in vitro studies. Preictal activation of interneurons began earliest (>4 min before seizure onset), increased most, was most prevalent in the subiculum, and was minimal in CA3. Preictal inactivation of interneurons was most common in CA1 (27% of interneurons) and included a putative ivy cell and parvalbumin-positive basket cell. Increased or decreased preictal activity correlated with whether interneurons fired faster or slower, respectively, during theta activity. Theta waves were more likely to occur before seizure onset, and increased preictal firing of subicular interneurons correlated with theta activity. Preictal changes by other hippocampal interneurons were largely independent of theta waves. Within seconds of seizure onset, many interneurons displayed a brief pause in firing and a later, longer drop that was associated with reduced action potential amplitude. These findings suggest that many interneurons inactivate during seizures, most increase their activity preictally, but some fail to do so at the critical time before seizure onset. PMID:25904809

  16. Low-frequency stimulation in anterior nucleus of thalamus alleviates kainate-induced chronic epilepsy and modulates the hippocampal EEG rhythm.

    PubMed

    Wang, Yi; Liang, Jiao; Xu, Cenglin; Wang, Ying; Kuang, Yifang; Xu, Zhenghao; Guo, Yi; Wang, Shuang; Gao, Feng; Chen, Zhong

    2016-02-01

    High-frequency stimulation (HFS) of the anterior nucleus of thalamus (ANT) is a new and alternative option for the treatment of intractable epilepsy. However, the responder rate is relatively low. The present study was designed to determine the effect of low-frequency stimulation (LFS) in ANT on chronic spontaneous recurrent seizures and related pathological pattern in intra-hippocampal kainate mouse model. We found that LFS (1 Hz, 100 μs, 300 μA), but not HFS (100 Hz, 100 μs, 30 μA), in bilateral ANT significantly decreased the frequency of spontaneous recurrent seizures, either non-convulsive focal seizures or tonic-clonic generalized seizures. The anti-epileptic effect persisted for one week after LFS cessation, which manifested as a long-term inhibition of the frequency of seizures with short (20-60 s) and intermediate duration (60-120 s). Meanwhile, LFS decreased the frequency of high-frequency oscillations (HFOs) and interictal spikes, two indicators of seizure severity, whereas HFS increased the HFO frequency. Furthermore, LFS decreased the power of the delta band and increased the power of the gamma band of hippocampal background EEG. In addition, LFS, but not HFS, improved the performance of chronic epileptic mice in objection-location task, novel objection recognition and freezing test. These results provide the first evidence that LFS in ANT alleviates kainate-induced chronic epilepsy and cognitive impairment, which may be related to the modulation of the hippocampal EEG rhythm. This may be of great therapeutic significance for clinical treatment of epilepsy with deep brain stimulation. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Intracranial investigation of a patient with nodular heterotopia and hippocampal sclerosis: dealing with a dual pathology.

    PubMed

    Ladino, Lady Diana; Dash, Chelsea; Wu, Adam; Tellez-Zenteno, Jose Francisco

    2017-06-01

    The pre-operative assessment and surgical management of patients with dual pathology is challenging. We describe a patient with drug-resistant focal epilepsy with hippocampal sclerosis and extensive periventricular nodular heterotopia in the same hemisphere. The semiology, scalp EEG, and imaging were divergent, but the presence of focal interictal and ictal epileptic discharges of the putative ictal onset zone resulted in successful localization of the epileptogenic zone. A less aggressive resection was performed based on intracranial EEG recording. The patient has been seizure-free for three years since resection. Electroclinical hypotheses and challenges in defining the epileptogenic network are discussed.

  18. Hippocampal TNFα Signaling Contributes to Seizure Generation in an Infection-Induced Mouse Model of Limbic Epilepsy.

    PubMed

    Patel, Dipan C; Wallis, Glenna; Dahle, E Jill; McElroy, Pallavi B; Thomson, Kyle E; Tesi, Raymond J; Szymkowski, David E; West, Peter J; Smeal, Roy M; Patel, Manisha; Fujinami, Robert S; White, H Steve; Wilcox, Karen S

    2017-01-01

    Central nervous system infection can induce epilepsy that is often refractory to established antiseizure drugs. Previous studies in the Theiler's murine encephalomyelitis virus (TMEV)-induced mouse model of limbic epilepsy have demonstrated the importance of inflammation, especially that mediated by tumor necrosis factor-α (TNFα), in the development of acute seizures. TNFα modulates glutamate receptor trafficking via TNF receptor 1 (TNFR1) to cause increased excitatory synaptic transmission. Therefore, we hypothesized that an increase in TNFα signaling after TMEV infection might contribute to acute seizures. We found a significant increase in both mRNA and protein levels of TNFα and the protein expression ratio of TNF receptors (TNFR1:TNFR2) in the hippocampus, a brain region most likely involved in seizure initiation, after TMEV infection, which suggests that TNFα signaling, predominantly through TNFR1, may contribute to limbic hyperexcitability. An increase in hippocampal cell-surface glutamate receptor expression was also observed during acute seizures. Although pharmacological inhibition of TNFR1-mediated signaling had no effect on acute seizures, several lines of genetically modified animals deficient in either TNFα or TNFRs had robust changes in seizure incidence and severity after TMEV infection. TNFR2 -/- mice were highly susceptible to developing acute seizures, suggesting that TNFR2-mediated signaling may provide beneficial effects during the acute seizure period. Taken together, the present results suggest that inflammation in the hippocampus, caused predominantly by TNFα signaling, contributes to hyperexcitability and acute seizures after TMEV infection. Pharmacotherapies designed to suppress TNFR1-mediated or augment TNFR2-mediated effects of TNFα may provide antiseizure and disease-modifying effects after central nervous system infection.

  19. Hippocampal TNFα Signaling Contributes to Seizure Generation in an Infection-Induced Mouse Model of Limbic Epilepsy

    PubMed Central

    Patel, Dipan C.; Wallis, Glenna; Dahle, E. Jill; McElroy, Pallavi B.; Thomson, Kyle E.; West, Peter J.; Smeal, Roy M.; Patel, Manisha; Fujinami, Robert S.; White, H. Steve

    2017-01-01

    Abstract Central nervous system infection can induce epilepsy that is often refractory to established antiseizure drugs. Previous studies in the Theiler’s murine encephalomyelitis virus (TMEV)-induced mouse model of limbic epilepsy have demonstrated the importance of inflammation, especially that mediated by tumor necrosis factor-α (TNFα), in the development of acute seizures. TNFα modulates glutamate receptor trafficking via TNF receptor 1 (TNFR1) to cause increased excitatory synaptic transmission. Therefore, we hypothesized that an increase in TNFα signaling after TMEV infection might contribute to acute seizures. We found a significant increase in both mRNA and protein levels of TNFα and the protein expression ratio of TNF receptors (TNFR1:TNFR2) in the hippocampus, a brain region most likely involved in seizure initiation, after TMEV infection, which suggests that TNFα signaling, predominantly through TNFR1, may contribute to limbic hyperexcitability. An increase in hippocampal cell-surface glutamate receptor expression was also observed during acute seizures. Although pharmacological inhibition of TNFR1-mediated signaling had no effect on acute seizures, several lines of genetically modified animals deficient in either TNFα or TNFRs had robust changes in seizure incidence and severity after TMEV infection. TNFR2–/– mice were highly susceptible to developing acute seizures, suggesting that TNFR2-mediated signaling may provide beneficial effects during the acute seizure period. Taken together, the present results suggest that inflammation in the hippocampus, caused predominantly by TNFα signaling, contributes to hyperexcitability and acute seizures after TMEV infection. Pharmacotherapies designed to suppress TNFR1-mediated or augment TNFR2-mediated effects of TNFα may provide antiseizure and disease-modifying effects after central nervous system infection. PMID:28497109

  20. Extracellular chelation of zinc does not affect hippocampal excitability and seizure-induced cell death in rats

    PubMed Central

    Lavoie, Nathalie; Peralta, Modesto R; Chiasson, Marilou; Lafortune, Kathleen; Pellegrini, Luca; Seress, László; Tóth, Katalin

    2007-01-01

    In the nervous system, zinc can influence synaptic responses and at extreme concentrations contributes to epileptic and ischaemic neuronal injury. Zinc can originate from synaptic vesicles, the extracellular space and from intracellular stores. In this study, we aimed to determine which of these zinc pools is responsible for the increased hippocampal excitability observed in zinc-depleted animals or following zinc chelation. Also, we investigated the source of intracellularly accumulating zinc in vulnerable neurons. Our data show that membrane-permeable and membrane-impermeable zinc chelators had little or no effect on seizure activity in the CA3 region. Furthermore, extracellular zinc chelation could not prevent the accumulation of lethal concentrations of zinc in dying neurons following epileptic seizures. At the electron microscopic level, zinc staining significantly increased at the presynaptic membrane of mossy fibre terminals in kainic acid-treated animals. These data indicate that intracellular but not extracellular zinc chelators could influence neuronal excitability and seizure-induced zinc accumulation observed in the cytosol of vulnerable neurons. PMID:17095563

  1. Assessment of seizure liability of Org 306039, a 5-HT2c agonist, using hippocampal brain slice and rodent EEG telemetry.

    PubMed

    Markgraf, Carrie G; DeBoer, Erik; Zhai, Jin; Cornelius, Lara; Zhou, Ying Ying; MacSweeney, Cliona

    2014-01-01

    Evaluation of the seizure potential for a CNS-targeted pharmaceutical compound before it is administered to humans is an important part of development. The current in vitro and in vivo studies were undertaken to characterize the seizure potential of the potent and selective 5-HT2c agonist Org 306039. Rat hippocampal slices (n=5) were prepared and Org 306039 was applied over a concentration range of 0-1000μM. Male Sprague-Dawley rats, implanted with telemetry EEG recording electrodes received either vehicle (n=4) or 100mg/kg Org 306039 (n=4) by oral gavage daily for 10days. EEG was recorded continuously for 22±1h post-dose each day. Post-dose behavior observations were conducted daily for 2h. Body temperature was measured at 1 and 2h post-dose. On Day 7, blood samples were drawn for pharmacokinetic analysis of Org 306039. In hippocampal slice, Org 306039 elicited a concentration-dependent increase in population spike area and number recorded from CA1 area, indicating seizure-genic potential. In telemetered rats, Org 306039 was associated with a decrease in body weight, a decrease in body temperature and the appearance of seizure-related behaviors and pre-seizure waveforms on EEG. One rat exhibited an overt seizure. Plasma concentrations of Org 306039 were similar among the 4 rats in the Org-treated group. Small group size made it difficult to determine a PK-PD relationship. These results indicate that the in vitro and in vivo models complement each other in the characterization of the seizure potential of CNS-targeted compounds such as the 5-HT2c agonist Org 306039. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Neuronal Ensemble Synchrony during Human Focal Seizures

    PubMed Central

    Ahmed, Omar J.; Harrison, Matthew T.; Eskandar, Emad N.; Cosgrove, G. Rees; Madsen, Joseph R.; Blum, Andrew S.; Potter, N. Stevenson; Hochberg, Leigh R.; Cash, Sydney S.

    2014-01-01

    Seizures are classically characterized as the expression of hypersynchronous neural activity, yet the true degree of synchrony in neuronal spiking (action potentials) during human seizures remains a fundamental question. We quantified the temporal precision of spike synchrony in ensembles of neocortical neurons during seizures in people with pharmacologically intractable epilepsy. Two seizure types were analyzed: those characterized by sustained gamma (∼40–60 Hz) local field potential (LFP) oscillations or by spike-wave complexes (SWCs; ∼3 Hz). Fine (<10 ms) temporal synchrony was rarely present during gamma-band seizures, where neuronal spiking remained highly irregular and asynchronous. In SWC seizures, phase locking of neuronal spiking to the SWC spike phase induced synchrony at a coarse 50–100 ms level. In addition, transient fine synchrony occurred primarily during the initial ∼20 ms period of the SWC spike phase and varied across subjects and seizures. Sporadic coherence events between neuronal population spike counts and LFPs were observed during SWC seizures in high (∼80 Hz) gamma-band and during high-frequency oscillations (∼130 Hz). Maximum entropy models of the joint neuronal spiking probability, constrained only on single neurons' nonstationary coarse spiking rates and local network activation, explained most of the fine synchrony in both seizure types. Our findings indicate that fine neuronal ensemble synchrony occurs mostly during SWC, not gamma-band, seizures, and primarily during the initial phase of SWC spikes. Furthermore, these fine synchrony events result mostly from transient increases in overall neuronal network spiking rates, rather than changes in precise spiking correlations between specific pairs of neurons. PMID:25057195

  3. High frequency oscillations (80–500 Hz) in the preictal period in patients with focal seizures

    PubMed Central

    Jacobs, Julia; Zelmann, Rina; Jirsch, Jeffrey; Chander, Rahul; Châtillon, Claude-Édouard; Dubeau, François; Gotman, Jean

    2013-01-01

    Summary Purpose Intracranial depth macroelectrode recordings from patients with focal seizures demonstrate interictal and ictal high frequency oscillations (HFOs, 80–500 Hz). These HFOs are more frequent in the seizure-onset zone (SOZ) and reported to be linked to seizure genesis. We evaluated whether HFO activity changes in a systematic way during the preictal period. Methods Fifteen minutes of preictal intracranial electroencephalography (EEG) recordings were evaluated in seven consecutive patients with well-defined SOZ. EEG was filtered at 500 Hz and sampled at 2,000 Hz. Ripples (80–250 Hz) and fast ripples (250–500 Hz) were visually marked, and spectral analysis was performed in seizure-onset as well as nonseizure-onset channels. Linear regressions fitted to the power trends corresponding to intervals of 1, 5, and 15 min before the seizure onset was calculated. Results Total rates of HFOs were significantly higher in the SOZ than outside. Preictal increases and decreases in HFO rates and band power could be detected in all patients, and they were not limited to the SOZs. These measures were very variable, and nosystematic trends were observed when comparing patients or seizures in the same patient. Discussion High frequencies in the range of 80–500 Hz are present during the preictal period and are more prominent in the SOZ. They do not change in a systematic way before seizure onset for the horizons we tested. The 80–500 Hz band may be used for the localization of seizure-onset areas but may be more difficult to use for seizure prediction purposes. PMID:19400871

  4. Transcranial focal stimulation via concentric ring electrodes reduced power of pentylenetetrazole-induced seizure activity in rat electroencephalogram.

    PubMed

    Makeyev, Oleksandr; Liu, Xiang; Koka, Kanthaiah; Kay, Steven M; Besio, Walter G

    2011-01-01

    As epilepsy affects approximately one percent of the world population, electrical stimulation of the brain has recently shown potential for additive seizure control therapy. In this study we applied noninvasive transcranial focal stimulation (TFS) via concentric ring electrodes on the scalp of rats after inducing seizures with pentylenetetrazole (PTZ) to assess the effect of TFS on the electrographic activity. Grand average power spectral densities were calculated to compare different stages of seizure development. They showed a significant difference between the TFS treated group and the control group. In case of the TFS treated group, after TFS, the power spectral density was reduced further towards a pre-seizure "baseline" than it was for the control group. The difference is the most drastic in delta, theta and alpha frequency bands. Application of general likelihood ratio test showed that TFS significantly (p<0.001) reduced the power of electrographic seizure activity in the TFS treated group compared to controls in more than 86% of the cases. These results suggest that TFS may have an anticonvulsant effect.

  5. Minimum Electric Field Exposure for Seizure Induction with Electroconvulsive Therapy and Magnetic Seizure Therapy.

    PubMed

    Lee, Won H; Lisanby, Sarah H; Laine, Andrew F; Peterchev, Angel V

    2017-05-01

    Lowering and individualizing the current amplitude in electroconvulsive therapy (ECT) has been proposed as a means to produce stimulation closer to the neural activation threshold and more focal seizure induction, which could potentially reduce cognitive side effects. However, the effect of current amplitude on the electric field (E-field) in the brain has not been previously linked to the current amplitude threshold for seizure induction. We coupled MRI-based E-field models with amplitude titrations of motor threshold (MT) and seizure threshold (ST) in four nonhuman primates (NHPs) to determine the strength, distribution, and focality of stimulation in the brain for four ECT electrode configurations (bilateral, bifrontal, right-unilateral, and frontomedial) and magnetic seizure therapy (MST) with cap coil on vertex. At the amplitude-titrated ST, the stimulated brain subvolume (23-63%) was significantly less than for conventional ECT with high, fixed current (94-99%). The focality of amplitude-titrated right-unilateral ECT (25%) was comparable to cap coil MST (23%), demonstrating that ECT with a low current amplitude and focal electrode placement can induce seizures with E-field as focal as MST, although these electrode and coil configurations affect differently specific brain regions. Individualizing the current amplitude reduced interindividual variation in the stimulation focality by 40-53% for ECT and 26% for MST, supporting amplitude individualization as a means of dosing especially for ECT. There was an overall significant correlation between the measured amplitude-titrated ST and the prediction of the E-field models, supporting a potential role of these models in dosing of ECT and MST. These findings may guide the development of seizure therapy dosing paradigms with improved risk/benefit ratio.

  6. Safety of the Transcranial Focal Electrical Stimulation via Tripolar Concentric Ring Electrodes for Hippocampal CA3 Subregion Neurons in Rats

    PubMed Central

    2017-01-01

    Epilepsy is a neurological disorder that affects approximately one percent of the world population. Noninvasive electrical brain stimulation via tripolar concentric ring electrodes has been proposed as an alternative/complementary therapy for seizure control. Previous results suggest its efficacy attenuating acute seizures in penicillin, pilocarpine-induced status epilepticus, and pentylenetetrazole-induced rat seizure models and its safety for the rat scalp, cortical integrity, and memory formation. In this study, neuronal counting was used to assess possible tissue damage in rats (n = 36) due to the single dose or five doses (given every 24 hours) of stimulation on hippocampal CA3 subregion neurons 24 hours, one week, and one month after the last stimulation dose. Full factorial analysis of variance showed no statistically significant difference in the number of neurons between control and stimulation-treated animals (p = 0.71). Moreover, it showed no statistically significant differences due to the number of stimulation doses (p = 0.71) nor due to the delay after the last stimulation dose (p = 0.96). Obtained results suggest that stimulation at current parameters (50 mA, 200 μs, 300 Hz, biphasic, charge-balanced pulses for 2 minutes) does not induce neuronal damage in the hippocampal CA3 subregion of the brain. PMID:29065603

  7. Safety of the Transcranial Focal Electrical Stimulation via Tripolar Concentric Ring Electrodes for Hippocampal CA3 Subregion Neurons in Rats.

    PubMed

    Mucio-Ramírez, Samuel; Makeyev, Oleksandr

    2017-01-01

    Epilepsy is a neurological disorder that affects approximately one percent of the world population. Noninvasive electrical brain stimulation via tripolar concentric ring electrodes has been proposed as an alternative/complementary therapy for seizure control. Previous results suggest its efficacy attenuating acute seizures in penicillin, pilocarpine-induced status epilepticus, and pentylenetetrazole-induced rat seizure models and its safety for the rat scalp, cortical integrity, and memory formation. In this study, neuronal counting was used to assess possible tissue damage in rats ( n = 36) due to the single dose or five doses (given every 24 hours) of stimulation on hippocampal CA3 subregion neurons 24 hours, one week, and one month after the last stimulation dose. Full factorial analysis of variance showed no statistically significant difference in the number of neurons between control and stimulation-treated animals ( p  = 0.71). Moreover, it showed no statistically significant differences due to the number of stimulation doses ( p  = 0.71) nor due to the delay after the last stimulation dose ( p  = 0.96). Obtained results suggest that stimulation at current parameters (50 mA, 200  μ s, 300 Hz, biphasic, charge-balanced pulses for 2 minutes) does not induce neuronal damage in the hippocampal CA3 subregion of the brain.

  8. Cerebellar Directed Optogenetic Intervention Inhibits Spontaneous Hippocampal Seizures in a Mouse Model of Temporal Lobe Epilepsy1 2

    PubMed Central

    Szabo, Gergely G.; Armstrong, Caren; Oijala, Mikko; Soltesz, Ivan

    2014-01-01

    Abstract Cover Figure Krook-Magnuson et al. report a bidirectional functional connectivity between the hippocampus and the cerebellum in a mouse model of temporal lobe epilepsy, and demonstrate that cerebellar directed on-demand optogenetic intervention can stop seizures recorded from the hippocampus. Temporal lobe epilepsy is often medically refractory and new targets for intervention are needed. We used a mouse model of temporal lobe epilepsy, on-line seizure detection, and responsive optogenetic intervention to investigate the potential for cerebellar control of spontaneous temporal lobe seizures. Cerebellar targeted intervention inhibited spontaneous temporal lobe seizures during the chronic phase of the disorder. We further report that the direction of modulation as well as the location of intervention within the cerebellum can affect the outcome of intervention. Specifically, on-demand optogenetic excitation or inhibition of parvalbumin-expressing neurons, including Purkinje cells, in the lateral or midline cerebellum results in a decrease in seizure duration. In contrast, a consistent reduction in spontaneous seizure frequency occurs uniquely with on-demand optogenetic excitation of the midline cerebellum, and was not seen with intervention directly targeting the hippocampal formation. These findings demonstrate that the cerebellum is a powerful modulator of temporal lobe epilepsy, and that intervention targeting the cerebellum as a potential therapy for epilepsy should be revisited. PMID:25599088

  9. Seizure characteristics of epilepsy in childhood after acute encephalopathy with biphasic seizures and late reduced diffusion.

    PubMed

    Ito, Yuji; Natsume, Jun; Kidokoro, Hiroyuki; Ishihara, Naoko; Azuma, Yoshiteru; Tsuji, Takeshi; Okumura, Akihisa; Kubota, Tetsuo; Ando, Naoki; Saitoh, Shinji; Miura, Kiyokuni; Negoro, Tamiko; Watanabe, Kazuyoshi; Kojima, Seiji

    2015-08-01

    The aim of this study was to clarify characteristics of post-encephalopathic epilepsy (PEE) in children after acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), paying particular attention to precise diagnosis of seizure types. Among 262 children with acute encephalopathy/encephalitis registered in a database of the Tokai Pediatric Neurology Society between 2005 and 2012, 44 were diagnosed with AESD according to the clinical course and magnetic resonance imaging (MRI) findings and were included in this study. Medical records were reviewed to investigate clinical data, MRI findings, neurologic outcomes, and presence or absence of PEE. Seizure types of PEE were determined by both clinical observation by pediatric neurologists and ictal video-electroencephalography (EEG) recordings. Of the 44 patients after AESD, 10 (23%) had PEE. The period between the onset of encephalopathy and PEE ranged from 2 to 39 months (median 8.5 months). Cognitive impairment was more severe in patients with PEE than in those without. Biphasic seizures and status epilepticus during the acute phase of encephalopathy did not influence the risk of PEE. The most common seizure type of PEE on clinical observation was focal seizures (n = 5), followed by epileptic spasms (n = 4), myoclonic seizures (n = 3), and tonic seizures (n = 2). In six patients with PEE, seizures were induced by sudden unexpected sounds. Seizure types confirmed by ictal video-EEG recordings were epileptic spasms and focal seizures with frontal onset, and all focal seizures were startle seizures induced by sudden acoustic stimulation. Intractable daily seizures remain in six patients with PEE. We demonstrate seizure characteristics of PEE in children after AESD. Epileptic spasms and startle focal seizures are common seizure types. The specific seizure types may be determined by the pattern of diffuse subcortical white matter injury in AESD and age-dependent reorganization of the brain

  10. Elevated expression of pleiotrophin in pilocarpine-induced seizures of immature rats and in pentylenetetrazole-induced hippocampal astrocytes in vitro.

    PubMed

    Zhang, Shuqin; Liang, Feng; Wang, Bing; Le, Yuan; Wang, Hua

    2014-03-01

    Pleiotrophin (PTN) is a secreted extracellular matrix (ECM)-associated cytokine that has emerged as an important neuromodulator with multiple neuronal functions. In the present study, we detected and compared the dynamic expression of PTN in the hippocampus and adjacent cortex of immature rats with pilocarpine-induced epilepsy. Moreover, we also confirmed the results by examining PTN expression in hippocampal astrocytes cultured in the presence of pentylenetetrazole (PTZ). Immunohistochemistry showed faint immunostaining of PTN in the control hippocampus and adjacent cortex. Notably, PTN immunoreactivity began to increase in relatively small cells in the hippocampus and adjacent cortex at 2h and 3 weeks after seizures, and the labeling intensity reached the maximum level in the hippocampus and adjacent cortex at 8 weeks after seizures. Furthermore, we also found that PTZ treatment significantly reduced astrocytic viability in a dose-dependent manner and time-dependently increased expression levels of PTN in hippocampal astrocytes. In conclusion, our data suggest that increased expression of PTN in the brain tissues may be involved in epileptogenesis. Copyright © 2013 Elsevier GmbH. All rights reserved.

  11. Seizure outcome after epilepsy surgery in patients with normal preoperative MRI.

    PubMed

    Chapman, K; Wyllie, E; Najm, I; Ruggieri, P; Bingaman, W; Lüders, J; Kotagal, P; Lachhwani, D; Dinner, D; Lüders, H O

    2005-05-01

    To determine outcome after epilepsy surgery in patients with normal preoperative magnetic resonance imaging (MRI). 24 adult and paediatric patients with normal preoperative MRIs were studied. They underwent epilepsy surgery between 1994 and 2001 and had at least one year of follow up. At the most recent follow up, nine patients (37%) were seizure-free and 18 (75%) had at least a 90% reduction in seizure frequency with weekly or monthly seizures. Seizure freedom was not significantly different after resections in frontal (5/9) or temporal regions (4/13) (p = 0.24, Fisher's exact test), or among patients with or without localising features on EEG, PET, or ictal SPECT. Subdural grids, used in 15 of 24 patients, helped tailor resections but were not associated with differences in outcome. Histopathology showed cortical dysplasia in 10 patients (42%), non-specific findings in 13 (54%), and hippocampal sclerosis in one (4%). Cortical dysplasia was seen in seven patients with frontal resection (78%) and non-specific findings in nine (69%) with temporal resection. Seizure outcome did not differ on the basis of location of resection or histopathology. While these results were less favourable than expected for patients with focal epileptogenic lesions seen on MRI, they represented worthwhile improvement for this patient population with high preoperative seizure burden. In this highly selected group, no single test or combination of tests further predicted postoperative seizure outcome.

  12. A meta-analysis of predictors of seizure freedom in the surgical management of focal cortical dysplasia.

    PubMed

    Rowland, Nathan C; Englot, Dario J; Cage, Tene A; Sughrue, Michael E; Barbaro, Nicholas M; Chang, Edward F

    2012-05-01

    Focal cortical dysplasia (FCD) is one of the most common causes of medically refractory epilepsy leading to surgery. However, seizure control outcomes reported in isolated surgical series are highly variable. As a result, it is not clear which variables are most crucial in predicting seizure freedom following surgery for FCD. The authors' aim was to determine the prognostic factors for seizure control in FCD by performing a meta-analysis of the published literature. A MEDLINE search of the published literature yielded 37 studies that met inclusion and exclusion criteria. Seven potential prognostic variables were determined from these studies and were dichotomized for analysis. For each variable, individual studies were weighted by inverse variance and combined to generate an odds ratio favoring seizure freedom. The methods complied with a standardized meta-analysis reporting protocol. Two thousand fourteen patients were included in the analysis. The overall rate of seizure freedom (Engel Class I) among patients undergoing surgery for FCD in the cohort of studies was 55.8% ± 16.2%. Partial seizures, a temporal location, detection with MRI, and a Type II Palmini histological classification were associated with higher rates of postoperative seizure control. As a treatment-related factor, complete resection of the anatomical or electrographic abnormality was the most important predictor overall of seizure freedom. Neither age nor electroencephalographic localization of the ictal onset significantly affected seizure freedom after surgery. Using a large population cohort pooled from the published literature, an analysis identified important factors that are prognostic in patients with epilepsy due to FCD. The most important of these factors-diagnostic imaging and resection-provide modalities through which improvements in the impact of FCD can be effected.

  13. Long-term safety and efficacy of eslicarbazepine acetate in patients with focal seizures: results of the 1-year ESLIBASE retrospective study.

    PubMed

    Villanueva, V; Serratosa, J M; Guillamón, E; Garcés, M; Giráldez, B G; Toledo, M; Salas-Puig, J; López González, F J; Flores, J; Rodríguez-Uranga, J; Castillo, A; Mauri, J A; Camacho, J L; López-Gomáriz, E; Giner, P; Torres, N; Palau, J; Molins, A

    2014-09-01

    Eslicarbazepine acetate (ESL) is a new antiepileptic drug (AED) licensed as adjunctive therapy in adults with partial-onset or focal seizures. To evaluate in a clinical practice setting the long-term efficacy and safety of ESL in patients with focal seizures. ESLIBASE was a retrospective study that included all patients with focal seizures who started ESL between January 2010 and July 2012 at 12 hospitals. ESL was prescribed individually according to real-life practice. Efficacy and safety were evaluated over 1 year. Switching from carbamazepine (CBZ) and oxcarbazepine (OXC) was assessed. Three hundred and twenty-seven patients were included; 78% of patients were taking ≥2 other AEDs at baseline. Most (87%) began ESL because of poor seizure control and 13% because of adverse events (AEs) with CBZ or OXC. After 1 year, 237 patients (72.4%) remained on ESL. At 3, 6 and 12 months, the responder rate was 46.3%, 57.9%, and 52.5%, and 21.0%, 28.0%, and 25.3% of patients were seizure free. The responder rate significantly increased when ESL was combined with a non-sodium channel-targeting drug (non-SC drug) (66.7%) versus an SC drug (47.7%; p<0.001). At 12 months, 40.7% of patients had ≥1 AE; AEs led to treatment discontinuation in 16.2%. Dizziness, nausea, and somnolence were the most common AEs. The tolerability profile improved in >50% of the patients who switched from CBZ or OXC to ESL because of AEs. ESL was well tolerated and effective in a real-world setting over 1 year. Side-effect profile improved when OXC and CBZ recipients were switched to ESL. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. The New Classification of Seizures by the International League Against Epilepsy 2017.

    PubMed

    Fisher, Robert S

    2017-06-01

    This review presents the newly developed International League Against Epilepsy (ILAE) 2017 classification of seizure types. The fundamental distinction is between seizures that begin focally in one hemisphere of the brain, generalized onset seizures that apparently originate in both hemispheres, and seizures of unknown onset. Focal seizures optionally can be subclassified according to whether awareness (a surrogate marker for consciousness) is intact or impaired. The next level of classification for focal seizures is motor (with subgroups automatisms, atonic, clonic, epileptic spasms, hyperkinetic, myoclonic, tonic), non-motor (with subgroups autonomic, behavior arrest, cognitive, emotional, sensory), and focal to bilateral tonic-clonic. Generalized seizures are categorized as motor (tonic-clonic, clonic, tonic, myoclonic, myoclonic-tonic-clonic, myoclonic-atonic, atonic, epileptic spasms) and non-motor/absence (typical, atypical, myoclonic, eyelid myoclonia). The classification allows new types of focal seizures and a few new generalized seizures, and clarifies terms used to name seizures.

  15. Frequent sleep-related bitemporal focal seizures in transient epileptic amnesia syndrome: Evidence from ictal video-EEG.

    PubMed

    Burkholder, David B; Jones, Amy L; Jones, David T; Fabris, Rachel R; Britton, Jeffrey W; Lagerlund, Terrence D; So, Elson L; Cascino, Gregory D; Worrell, Gregory A; Shin, Cheolsu; St Louis, Erik K

    2017-06-01

    Two patients who shared similar presenting clinical features of anterograde and retrograde autobiographical amnesia typical of transient epileptic amnesia (TEA) underwent prolonged video electroencephalogram (VEEG) monitoring and were found to have sleep-activated epileptiform activity and frequent subclinical bitemporal seizures predominantly during sleep. Case 1 is a 59-year-old woman whose presenting complaint was memory impairment. Over 18 months, she had three distinct 8-h-long episodes of confusion and disorientation with persistent anterograde and retrograde autobiographical amnesia. VEEG recorded frequent interictal bitemporal sharp waves confined to sleep, and 14 subclinical seizures, also mostly during sleep. Case 2 is a 50-year-old woman with known focal epilepsy also presented with memory complaints. Over the course of 1 year, she had two discrete 2-h-long episodes of amnesia, with ongoing anterograde and retrograde autobiographical amnesia. VEEG recorded independent bitemporal sharp waves, and 14 subclinical seizures during sleep and drowsiness. Memory impairment improved in both patients with successful treatment of their seizures. Although the etiology of accelerated long-term forgetting (ALF) and remote memory impairment (RMI) in transient epileptic amnesia (TEA) is unknown, these cases suggest frequent sleep-related seizures may contribute, and they highlight the importance of video-EEG monitoring.

  16. Why are seizures rare in rapid eye movement sleep? Review of the frequency of seizures in different sleep stages.

    PubMed

    Ng, Marcus; Pavlova, Milena

    2013-01-01

    Since the formal characterization of sleep stages, there have been reports that seizures may preferentially occur in certain phases of sleep. Through ascending cholinergic connections from the brainstem, rapid eye movement (REM) sleep is physiologically characterized by low voltage fast activity on the electroencephalogram, REMs, and muscle atonia. Multiple independent studies confirm that, in REM sleep, there is a strikingly low proportion of seizures (~1% or less). We review a total of 42 distinct conventional and intracranial studies in the literature which comprised a net of 1458 patients. Indexed to duration, we found that REM sleep was the most protective stage of sleep against focal seizures, generalized seizures, focal interictal discharges, and two particular epilepsy syndromes. REM sleep had an additional protective effect compared to wakefulness with an average 7.83 times fewer focal seizures, 3.25 times fewer generalized seizures, and 1.11 times fewer focal interictal discharges. In further studies REM sleep has also demonstrated utility in localizing epileptogenic foci with potential translation into postsurgical seizure freedom. Based on emerging connectivity data in sleep, we hypothesize that the influence of REM sleep on seizures is due to a desynchronized EEG pattern which reflects important connectivity differences unique to this sleep stage.

  17. Fast spiking interneuron control of seizure propagation in a cortical slice model of focal epilepsy

    PubMed Central

    Cammarota, Mario; Losi, Gabriele; Chiavegato, Angela; Zonta, Micaela; Carmignoto, Giorgio

    2013-01-01

    In different animal models of focal epilepsy, seizure-like ictal discharge propagation is transiently opposed by feedforward inhibition. The specific cellular source of this signal and the mechanism by which inhibition ultimately becomes ineffective are, however, undefined. We used a brain slice model to study how focal ictal discharges that were repetitively evoked from the same site, and at precise times, propagate across the cortex. We used Ca2+ imaging and simultaneous single/dual cell recordings from pyramidal neurons (PyNs) and different classes of interneurons in rodents, including G42 and GIN transgenic mice expressing the green fluorescence protein in parvalbumin (Pv)-fast spiking (FS) and somatostatin (Som) interneurons, respectively. We found that these two classes of interneurons fired intensively shortly after ictal discharge generation at the focus. The inhibitory barrages that were recorded in PyNs occurred in coincidence with Pv-FS, but not with Som interneuron burst discharges. Furthermore, the strength of inhibitory barrages increased or decreased in parallel with increased or decreased firing in Pv-FS interneurons but not in Som interneurons. A firing impairment of Pv-FS interneurons caused by a membrane depolarization was found to precede ictal discharge onset in neighbouring pyramidal neurons. This event may account for the collapse of local inhibition that allows spatially defined clusters of PyNs to be recruited into propagating ictal discharges. Our study demonstrates that Pv-FS interneurons are a major source of the inhibitory barrages that oppose ictal discharge propagation and raises the possibility that targeting Pv-FS interneurons represents a new therapeutic strategy to prevent the generalization of human focal seizures. PMID:23207591

  18. Seizure outcome after epilepsy surgery in patients with normal preoperative MRI

    PubMed Central

    Chapman, K; Wyllie, E; Najm, I; Ruggieri, P; Bingaman, W; Luders, J; Kotagal, P; Lachhwani, D; Dinner, D; Luders, H

    2005-01-01

    Objective: To determine outcome after epilepsy surgery in patients with normal preoperative magnetic resonance imaging (MRI). Methods: 24 adult and paediatric patients with normal preoperative MRIs were studied. They underwent epilepsy surgery between 1994 and 2001 and had at least one year of follow up. Results: At the most recent follow up, nine patients (37%) were seizure-free and 18 (75%) had at least a 90% reduction in seizure frequency with weekly or monthly seizures. Seizure freedom was not significantly different after resections in frontal (5/9) or temporal regions (4/13) (p = 0.24, Fisher's exact test), or among patients with or without localising features on EEG, PET, or ictal SPECT. Subdural grids, used in 15 of 24 patients, helped tailor resections but were not associated with differences in outcome. Histopathology showed cortical dysplasia in 10 patients (42%), non-specific findings in 13 (54%), and hippocampal sclerosis in one (4%). Cortical dysplasia was seen in seven patients with frontal resection (78%) and non-specific findings in nine (69%) with temporal resection. Seizure outcome did not differ on the basis of location of resection or histopathology. Conclusions: While these results were less favourable than expected for patients with focal epileptogenic lesions seen on MRI, they represented worthwhile improvement for this patient population with high preoperative seizure burden. In this highly selected group, no single test or combination of tests further predicted postoperative seizure outcome. PMID:15834032

  19. Should consciousness describe seizures and what terms should be applied? Epilepsia's survey results.

    PubMed

    Mathern, Gary W; Beninsig, Laurie; Nehlig, Astrid

    2015-03-01

    From May to September 2014, Epilepsia conducted an online survey seeking opinions on whether consciousness should be used in describing focal and generalized seizures, and what terms should be applied to describe focal seizures with loss of awareness and amnesia. This study reports the findings of that survey. Two questions asked if consciousness should be used to classify seizures and what terms should be applied. Another four questions addressed demographic information. Of 209 individuals that started the poll, 147 (70.3%) completing it, and most that completed it were epileptologists (66%) from Europe (41%) and North America (27%). A majority (64%) indicated that the presence or absence of consciousness should be used to describe focal and generalized seizures, whereas 23% said it should not be used. When asked what term should be used to describe focal seizures with altered awareness and amnesia, 36% said focal impaired consciousness seizures (FICS), 30% selected complex partial seizures (CPS), and 16% answered focal dyscognitive seizures. This survey indicates that most responders prefer that consciousness be considered in the description of focal and generalized seizures, despite the difficulty in determining awareness clinically. Furthermore, responders could not agree on a single term that could be used to define focal seizures with loss of awareness and amnesia. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

  20. Generalized versus partial reflex seizures: a review.

    PubMed

    Italiano, Domenico; Ferlazzo, Edoardo; Gasparini, Sara; Spina, Edoardo; Mondello, Stefania; Labate, Angelo; Gambardella, Antonio; Aguglia, Umberto

    2014-08-01

    In this review we assess our currently available knowledge about reflex seizures with special emphasis on the difference between "generalized" reflex seizures induced by visual stimuli, thinking, praxis and language tasks, and "focal" seizures induced by startle, eating, music, hot water, somatosensory stimuli and orgasm. We discuss in particular evidence from animal, clinical, neurophysiological and neuroimaging studies supporting the concept that "generalized" reflex seizures, usually occurring in the setting of IGE, should be considered as focal seizures with quick secondary generalization. We also review recent advances in genetic and therapeutic approach of reflex seizures. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  1. Outcome of epilepsy surgery in focal cortical dysplasia

    PubMed Central

    Kral, T; Clusmann, H; Blumcke, I; Fimmers, R; Ostertun, B; Kurthen, M; Schramm, J

    2003-01-01

    Objective: To describe the outcome of surgery in patients with drug resistant epilepsy and a histopathological diagnosis of focal cortical dysplasia. Methods and subjects: Analysis of histories and presurgical and follow up data was carried out in 53 patients with a histological diagnosis of focal cortical dysplasia. Their mean age was 24.0 years (range 5 to 46), and they included 14 children and adolescents. Mean age at seizure onset was 12.4 years (0.4 to 36) and mean seizure duration was 11.6 years (1 to 45). Results: The presurgical detection rate of focal cortical dysplasia with magnetic resonance imaging (MRI) was 96%. There were 24 temporal and 29 extratemporal resections; additional multiple subpial transections were done in 12 cases to prevent spread of seizure discharges. There was a 6% rate of complications with permanent neurological deficit, but no deaths. All resected specimens were classified by neuropathological criteria as focal cortical dysplasia. Balloon cells were seen in most cases of extratemporal focal cortical dysplasia. After a mean follow up of 50 months, 38 patients (72%) were seizure-free, two (4%) had less than two seizures a year, nine (17%) had a reduction of seizure frequency of more than 75%, and four (8%) had no improvement. Seizure outcome was similar after temporal and extratemporal surgery. The patients in need of multilobar surgery had the poorest outcome. Conclusions: Circumscribed lesionectomy of focal dysplastic lesions provides seizure relief in patients with chronic drug resistant temporal and extratemporal epilepsy. There was a trend for the best seizure outcome to be in patients with early presurgical evaluation and early surgery, and in whom lesions were identified on the preoperative MRI studies. PMID:12531945

  2. The effects of early-life seizures on hippocampal dendrite development and later-life learning and memory.

    PubMed

    Casanova, J R; Nishimura, Masataka; Swann, John W

    2014-04-01

    Severe childhood epilepsy is commonly associated with intellectual developmental disabilities. The reasons for these cognitive deficits are likely multifactorial and will vary between epilepsy syndromes and even among children with the same syndrome. However, one factor these children have in common is the recurring seizures they experience - sometimes on a daily basis. Supporting the idea that the seizures themselves can contribute to intellectual disabilities are laboratory results demonstrating spatial learning and memory deficits in normal mice and rats that have experienced recurrent seizures in infancy. Studies reviewed here have shown that seizures in vivo and electrographic seizure activity in vitro both suppress the growth of hippocampal pyramidal cell dendrites. A simplification of dendritic arborization and a resulting decrease in the number and/or properties of the excitatory synapses on them could help explain the observed cognitive disabilities. There are a wide variety of candidate mechanisms that could be involved in seizure-induced growth suppression. The challenge is designing experiments that will help focus research on a limited number of potential molecular events. Thus far, results suggest that growth suppression is NMDA receptor-dependent and associated with a decrease in activation of the transcription factor CREB. The latter result is intriguing since CREB is known to play an important role in dendrite growth. Seizure-induced dendrite growth suppression may not occur as a single process in which pyramidal cells dendrites simply stop growing or grow slower compared to normal neurons. Instead, recent results suggest that after only a few hours of synchronized epileptiform activity in vitro dendrites appear to partially retract. This acute response is also NMDA receptor dependent and appears to be mediated by the Ca(+2)/calmodulin-dependent phosphatase, calcineurin. An understanding of the staging of seizure-induced growth suppression and the

  3. Familial temporal lobe epilepsy due to focal cortical dysplasia type IIIa.

    PubMed

    Fabera, Petr; Krijtova, Hana; Tomasek, Martin; Krysl, David; Zamecnik, Josef; Mohapl, Milan; Jiruska, Premysl; Marusic, Petr

    2015-09-01

    Focal cortical dysplasia (FCD) represents a common cause of refractory epilepsy. It is considered a sporadic disorder, but its occasional familial occurrence suggests the involvement of genetic mechanisms. Siblings with intractable epilepsy were referred for epilepsy surgery evaluation. Both patients were examined using video-EEG monitoring, MRI examination and PET imaging. They underwent left anteromedial temporal lobe resection. Electroclinical features pointed to left temporal lobe epilepsy and MRI examination revealed typical signs of left-sided hippocampal sclerosis and increased white matter signal intensity in the left temporal pole. PET examination confirmed interictal hypometabolism in the left temporal lobe. Histopathological examination of resected tissue demonstrated the presence FCD type IIIa, i.e. hippocampal sclerosis and focal cortical dysplasia in the left temporal pole. We present a unique case of refractory mesial temporal lobe epilepsy in siblings, characterized by an identical clinical profile and histopathology of FCD type IIIa, who were successfully treated by epilepsy surgery. The presence of such a high concordance between the clinical and morphological data, together with the occurrence of epilepsy and febrile seizures in three generations of the family pedigree points towards a possible genetic nature of the observed FCD type IIIa. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  4. Picrotoxin-induced seizures modified by morphine and opiate antagonists.

    PubMed

    Thomas, J; Nores, W L; Kenigs, V; Olson, G A; Olson, R D

    1993-07-01

    The effects of naloxone, Tyr-MIF-1, and MIF-1 on morphine-mediated changes in susceptibility to picrotoxin-induced seizures were studied. Rats were pretreated with naloxone, MIF-1, Tyr-MIF-1, or saline. At 15-min intervals, they received a second pretreatment of morphine or saline and then were tested for seizures following a convulsant dose of picrotoxin. Several parameters of specific categories of seizures were scored. Morphine increased the number of focal seizure episodes, duration of postseizure akinesis, and incidence of generalized clonic seizures. Naloxone tended to block the morphine-mediated changes in susceptibility. Tyr-MIF-1 had effects similar to naloxone on duration of postseizure immobility but tended to potentiate the effects of morphine on focal seizure episodes. The effects of morphine and the opiate antagonists on focal seizure episodes and postseizure duration suggest the general involvement of several types of opiate receptors in these picrotoxin-induced behaviors. However, the observation of antagonistic effects for Tyr-MIF-1 on immobility but agonistic effects for focal seizures suggests that the type of effect exerted by opiate agents may depend upon other neuronal variables.

  5. Effects of AT1 receptor antagonism on kainate-induced seizures and concomitant changes in hippocampal extracellular noradrenaline, serotonin, and dopamine levels in Wistar-Kyoto and spontaneously hypertensive rats.

    PubMed

    Tchekalarova, Jana; Loyens, Ellen; Smolders, Ilse

    2015-05-01

    In the management of epilepsy, AT1 receptor antagonists have been suggested as an additional treatment strategy. A hyperactive brain angiotensin (Ang) II system and upregulated AT1 receptors are implicated in the cerebrovascular alterations in a genetic form of hypertension. Uncontrolled hypertension could also, in turn, be a risk factor for a seizure threshold decrease and development of epileptogenesis. The present study aimed to assess the effects of the selective AT1 receptor antagonist ZD7155 on kainic acid (KA)-induced status epilepticus (SE) development and accompanying changes in the hippocampal extracellular (EC) neurotransmitter levels of noradrenaline (NAD), serotonin (5-HT), and dopamine (DA) in spontaneously hypertensive rats (SHRs) and their parent strain Wistar-Kyoto (WKY) rats, since monoamines are well-known neurotransmitters involved in mechanisms of both epilepsy and hypertension. Status epilepticus was evoked in freely moving rats by a repetitive intraperitoneal (i.p.) administration of KA in subconvulsant doses. In the treatment group, ZD7155 (5mg/kg i.p.) was coadministered with the first KA injection. Spontaneously hypertensive rats exhibited higher susceptibility to SE than WKY rats, but the AT1 receptor antagonist did not alter the development of SE in SHRs or in WKY rats. In vivo microdialysis demonstrated significant KA-induced increases of the hippocampal NAD and DA levels in SHRs and of NAD, 5-HT, and DA in WKY rats. Although SHRs developed more severe seizures while receiving a lower dose of KA compared to WKY rats, AT1 receptor antagonism completely prevented all KA-induced increases of hippocampal monoamine levels in both rat strains without affecting seizure development per se. These results suggest a lack of direct relationship between KA-induced seizure susceptibility and adaptive changes of hippocampal NAD, 5-HT, and DA levels in the effects of ZD7155 in WKY rats and SHRs. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Requirement of longitudinal synchrony of epileptiform discharges in the hippocampus for seizure generation: a pilot study.

    PubMed

    Umeoka, Shuichi C; Lüders, Hans O; Turnbull, John P; Koubeissi, Mohamad Z; Maciunas, Robert J

    2012-03-01

    The goal in this study was to assess the role of longitudinal hippocampal circuits in the generation of interictal and ictal activity in temporal lobe epilepsy (TLE) and to evaluate the effects of multiple hippocampal transections (MHT). In 6 patients with TLE, the authors evaluated the synchrony of hippocampal interictal and ictal epileptiform discharges by using a cross-correlation analysis, and the effect of MHT on hippocampal interictal spikes was studied. Five of the 6 patients were studied with depth electrodes, and epilepsy surgery was performed in 4 patients (anterior temporal lobectomy in 1 and MHT in 3). Four hundred eighty-two (95.1%) of 507 hippocampal spikes showed an anterior-to-posterior propagation within the hippocampus, with a fixed peak-to-peak interval. During seizures, a significant increase of synchronization between different hippocampal regions and between the hippocampus and the ipsilateral anterior parahippocampal gyrus was observed in all seizures. An ictal increase in synchronization between the hippocampus and ipsilateral amygdala was seen in only 24.1% of the seizures. No changes in synchronization were noticed during seizures between the hippocampi and the amygdala on either side. The structure leading the epileptic seizures varied over time during a given seizure and also from one seizure to another. Spike analysis during MHT demonstrated that there were two spike populations that reacted differently to this procedure--namely, 1) spikes that showed maximum amplitude at the head of the hippocampus (type H); and 2) spikes that showed the highest amplitude at the hippocampal body (type B). A striking decrease in amplitude and frequency of type B spikes was noticed in all 3 patients after transections at the head or anterior portion of the hippocampal body. Type H spikes were seen in 2 cases and did not change in amplitude and frequency throughout MHT. Type B spikes showed constantly high cross-correlation values in different derivations

  7. Pediatric epilepsy surgery: long-term 5-year seizure remission and medication use.

    PubMed

    Hauptman, Jason S; Pedram, Kayvon; Sison, Christia Angela; Sankar, Raman; Salamon, Noriko; Vinters, Harry V; Mathern, Gary W

    2012-11-01

    It is unclear whether long-term seizure outcomes in children are similar to those in adult epilepsy surgery patients. To determine 5-year outcomes and antiepilepsy drug (AED) use in pediatric epilepsy surgery patients from a single institution. The cohort consisted of children younger than 18 years of age whose 5-year outcome data would have been available by 2010. Comparisons were made between patients with and without 5-year data (n = 338), patients with 5-year data for seizure outcome (n = 257), and seizure-free patients on and off AEDs (n = 137). Five-year data were available from 76% of patients. More seizure-free patients with focal resections for hippocampal sclerosis and tumors lacked 5-year data compared with other cases. Of those with 5-year data, 53% were continuously seizure free, 18% had late seizure recurrence, 3% became seizure free after initial failure, and 25% were never seizure free. Patients were more likely to be continuously seizure free if their surgery was performed during the period 2001 to 2005 (68%) compared with surgery performed from 1996 to 2000 (61%), 1991 to 1995 (36%), and 1986 to 1990 (46%). More patients had 1 or fewer seizures per month in the late seizure recurrence (47%) compared with the not seizure-free group (20%). Four late deaths occurred in the not seizure-free group compared with 1 in the seizure-free group. Of patients who were continuously seizure free, 55% were not taking AEDs, and more cortical dysplasia patients (74%) had stopped taking AEDs compared with hemimegalencephaly patients (18%). In children, 5-year outcomes improved over 20 years of clinical experience. Our results are similar to those of adult epilepsy surgery patients despite mostly extratemporal and hemispheric operations for diverse developmental etiologies.

  8. Instruction manual for the ILAE 2017 operational classification of seizure types.

    PubMed

    Fisher, Robert S; Cross, J Helen; D'Souza, Carol; French, Jacqueline A; Haut, Sheryl R; Higurashi, Norimichi; Hirsch, Edouard; Jansen, Floor E; Lagae, Lieven; Moshé, Solomon L; Peltola, Jukka; Roulet Perez, Eliane; Scheffer, Ingrid E; Schulze-Bonhage, Andreas; Somerville, Ernest; Sperling, Michael; Yacubian, Elza Márcia; Zuberi, Sameer M

    2017-04-01

    This companion paper to the introduction of the International League Against Epilepsy (ILAE) 2017 classification of seizure types provides guidance on how to employ the classification. Illustration of the classification is enacted by tables, a glossary of relevant terms, mapping of old to new terms, suggested abbreviations, and examples. Basic and extended versions of the classification are available, depending on the desired degree of detail. Key signs and symptoms of seizures (semiology) are used as a basis for categories of seizures that are focal or generalized from onset or with unknown onset. Any focal seizure can further be optionally characterized by whether awareness is retained or impaired. Impaired awareness during any segment of the seizure renders it a focal impaired awareness seizure. Focal seizures are further optionally characterized by motor onset signs and symptoms: atonic, automatisms, clonic, epileptic spasms, or hyperkinetic, myoclonic, or tonic activity. Nonmotor-onset seizures can manifest as autonomic, behavior arrest, cognitive, emotional, or sensory dysfunction. The earliest prominent manifestation defines the seizure type, which might then progress to other signs and symptoms. Focal seizures can become bilateral tonic-clonic. Generalized seizures engage bilateral networks from onset. Generalized motor seizure characteristics comprise atonic, clonic, epileptic spasms, myoclonic, myoclonic-atonic, myoclonic-tonic-clonic, tonic, or tonic-clonic. Nonmotor (absence) seizures are typical or atypical, or seizures that present prominent myoclonic activity or eyelid myoclonia. Seizures of unknown onset may have features that can still be classified as motor, nonmotor, tonic-clonic, epileptic spasms, or behavior arrest. This "users' manual" for the ILAE 2017 seizure classification will assist the adoption of the new system. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  9. Determining the relationship between sleep architecture, seizure variables and memory in patients with focal epilepsy.

    PubMed

    Miller, Laurie A; Ricci, Monica; van Schalkwijk, Frank J; Mohamed, Armin; van der Werf, Ysbrand D

    2016-06-01

    Sleep has been shown to be important to memory. Both sleep and memory have been found to be abnormal in patients with epilepsy. In this study, we explored the effects that nocturnal epileptiform discharges and the presence of a hippocampal lesion have on sleep patterns and memory. Twenty-five patients with focal epilepsy who underwent a 24-hr ambulatory EEG also completed the Everyday Memory Questionnaire (EMQ). The EEG record was scored for length of time spent in the various sleep stages, time spent awake after sleep onset, and rapid eye movement (REM) latency. Of these sleep variables, only REM latency differed when the epilepsy patients were divided on the bases of either presence/absence of nocturnal discharges or presence/absence of a hippocampal lesion. In both cases, presence of the abnormality was associated with longer latency. Furthermore, longer REM latency was found to be a better predictor of EMQ score than either number of discharges or presence of a hippocampal lesion. Longer REM latency was associated with a smaller percentage of time spent in slow-wave sleep in the early part of the night and may serve as a particularly sensitive marker to disturbances in sleep architecture. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  10. Focal CA3 hippocampal subfield atrophy following LGI1 VGKC-complex antibody limbic encephalitis

    PubMed Central

    Miller, Thomas D.; Chong, Trevor T.-J.; Aimola Davies, Anne M.; Ng, Tammy W.C.; Johnson, Michael R.; Irani, Sarosh R.; Vincent, Angela; Husain, Masud; Jacob, Saiju; Maddison, Paul; Kennard, Christopher; Gowland, Penny A.

    2017-01-01

    Magnetic resonance imaging has linked chronic voltage-gated potassium channel (VGKC) complex antibody-mediated limbic encephalitis with generalized hippocampal atrophy. However, autoantibodies bind to specific rodent hippocampal subfields. Here, human hippocampal subfield (subiculum, cornu ammonis 1-3, and dentate gyrus) targets of immunomodulation-treated LGI1 VGKC-complex antibody-mediated limbic encephalitis were investigated using in vivo ultra-high resolution (0.39 × 0.39 × 1.0 mm3) 7.0 T magnetic resonance imaging [n = 18 patients, 17 patients (94%) positive for LGI1 antibody and one patient negative for LGI1/CASPR2 but positive for VGKC-complex antibodies, mean age: 64.0 ± 2.55 years, median 4 years post-limbic encephalitis onset; n = 18 controls]. First, hippocampal subfield quantitative morphometry indicated significant volume loss confined to bilateral CA3 [F(1,34) = 16.87, P < 0.0001], despite hyperintense signal evident in 5 of 18 patients on presentation. Second, early and later intervention (<3 versus >3 months from symptom onset) were associated with CA3 atrophy. Third, whole-brain voxel-by-voxel morphometry revealed no significant grey matter loss. Fourth, CA3 subfield atrophy was associated with severe episodic but not semantic amnesia for postmorbid autobiographical events that was predicted by variability in CA3 volume. The results raise important questions about the links with histopathology, the impact of the observed focal atrophy on other CA3-mediated reconstructive and episodic mechanisms, and the role of potential antibody-mediated pathogenicity as part of the pathophysiology cascade in humans. PMID:28369215

  11. Focal electrically administered seizure therapy: a novel form of ECT illustrates the roles of current directionality, polarity, and electrode configuration in seizure induction.

    PubMed

    Spellman, Timothy; Peterchev, Angel V; Lisanby, Sarah H

    2009-07-01

    Electroconvulsive therapy (ECT) is a mainstay in the treatment of severe, medication-resistant depression. The antidepressant efficacy and cognitive side effects of ECT are influenced by the position of the electrodes on the head and by the degree to which the electrical stimulus exceeds the threshold for seizure induction. However, surprisingly little is known about the effects of other key electrical parameters such as current directionality, polarity, and electrode configuration. Understanding these relationships may inform the optimization of therapeutic interventions to improve their risk/benefit ratio. To elucidate these relationships, we evaluated a novel form of ECT (focal electrically administered seizure therapy, FEAST) that combines unidirectional stimulation, control of polarity, and an asymmetrical electrode configuration, and contrasted it with conventional ECT in a nonhuman primate model. Rhesus monkeys had their seizure thresholds determined on separate days with ECT conditions that crossed the factors of current directionality (unidirectional or bidirectional), electrode configuration (standard bilateral or FEAST (small anterior and large posterior electrode)), and polarity (assignment of anode and cathode in unidirectional stimulation). Ictal expression and post-ictal suppression were quantified through scalp EEG. Findings were replicated and extended in a second experiment with the same subjects. Seizures were induced in each of the 75 trials, including 42 FEAST procedures. Seizure thresholds were lower with unidirectional than with bidirectional stimulation (p<0.0001), and lower in FEAST than in bilateral ECS (p=0.0294). Ictal power was greatest in posterior-anode unidirectional FEAST, and post-ictal suppression was strongest in anterior-anode FEAST (p=0.0008 and p=0.0024, respectively). EEG power was higher in the stimulated hemisphere in posterior-anode FEAST (p=0.0246), consistent with the anode being the site of strongest activation. These

  12. Partial psychic seizures and brain organization.

    PubMed

    Ardila, A; Montañes, P; Bernal, B; Serpa, A; Ruiz, E

    1986-08-01

    This research was an attempt to determine the cerebral areas involved in focal epileptic seizures accompanied by psychic manifestations. Six types of partial seizures involving psychic symptomatology and phonatory seizures were included in the study. Sixty-one clinical records of focal epilepsy, which had been revealed by means of a CT-scan examination, were analyzed and a subsample of 25 patients with psychic symptoms was selected. The scans taken of the lesions were transferred to a six-level standard template built for this purpose. Subsequently, templates of patients with the same type of seizures were superimposed. The critical zones for the seven types of seizures studied are presented. A clear correlation was found between these results and our present knowledge of functional brain organization.

  13. Surgical treatment of patients with single and dual pathology: relevance of lesion and of hippocampal atrophy to seizure outcome.

    PubMed

    Li, L M; Cendes, F; Watson, C; Andermann, F; Fish, D R; Dubeau, F; Free, S; Olivier, A; Harkness, W; Thomas, D G; Duncan, J S; Sander, J W; Shorvon, S D; Cook, M J; Arnold, D L

    1997-02-01

    Modern neuroimaging can disclose epileptogenic lesions in many patients with partial epilepsy and, at times, display the coexistence of hippocampal atrophy in addition to an extrahippocampal lesion (dual pathology). We studied the postoperative seizure outcome of 64 patients with lesional epilepsy (median follow-up, 30 months) and considered separately the surgical results in the 51 patients with a single lesion and in the 13 who had dual pathology. In patients with a single lesion, 85% were seizure free or significantly improved (Engel's class I-II) when the lesion was totally removed compared with only 40% when there was incomplete resection (p < 0.007). All three patients with dual pathology who had both the lesion and the atrophic hippocampus removed became seizure free. In contrast, only 2 of the 10 patients with dual pathology undergoing surgery aimed at the lesion or at the hippocampus alone became seizure free (p < 0.05), although 4 of them showed significant improvement (Engel's class II). We conclude that the outcome in patients with single epileptogenic lesions is usually dependent upon the completeness of lesion resection. In patients with dual pathology, surgery should, if possible, include resection of both the lesion and the atrophic hippocampus.

  14. Seizure-onset patterns in focal cortical dysplasia and neurodevelopmental tumors: Relationship with surgical prognosis and neuropathologic subtypes.

    PubMed

    Lagarde, Stanislas; Bonini, Francesca; McGonigal, Aileen; Chauvel, Patrick; Gavaret, Martine; Scavarda, Didier; Carron, Romain; Régis, Jean; Aubert, Sandrine; Villeneuve, Nathalie; Giusiano, Bernard; Figarella-Branger, Dominique; Trebuchon, Agnès; Bartolomei, Fabrice

    2016-09-01

    The study of intracerebral electroencephalography (EEG) seizure-onset patterns is crucial to accurately define the epileptogenic zone and guide successful surgical resection. It also raises important pathophysiologic issues concerning mechanisms of seizure generation. Until now, several seizure-onset patterns have been described using distinct recording methods (subdural, depth electrode), mostly in temporal lobe epilepsies or with heterogeneous neocortical lesions. We analyzed data from a cohort of 53 consecutive patients explored by stereoelectroencephalography (SEEG) and with pathologically confirmed malformation of cortical development (MCD; including focal cortical dysplasia [FCD] and neurodevelopmental tumors [NDTs]). We identified six seizure-onset patterns using visual and time-frequency analysis: low-voltage fast activity (LVFA); preictal spiking followed by LVFA; burst of polyspikes followed by LVFA; slow wave/DC shift followed by LVFA; theta/alpha sharp waves; and rhythmic spikes/spike-waves. We found a high prevalence of patterns that included LVFA (83%), indicating nevertheless that LVFA is not a constant characteristic of seizure onset. An association between seizure-onset patterns and histologic types was found (p = 001). The more prevalent patterns were as follows: (1) in FCD type I LVFA (23.1%) and slow wave/baseline shift followed by LVFA (15.4%); (2) in FCD type II burst of polyspikes followed by LVFA (31%), LVFA (27.6%), and preictal spiking followed by LVFA (27.6%); (3) in NDT, LVFA (54.5%). We found that a seizure-onset pattern that included LVFA was associated with favorable postsurgical outcome, but the completeness of the EZ resection was the sole independent predictive variable. Six different seizure-onset patterns can be described in FCD and NDT. Better postsurgical outcome is associated with patterns that incorporate LVFA. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

  15. Ketogenic diet change cPLA2/clusterin and autophagy related gene expression and correlate with cognitive deficits and hippocampal MFs sprouting following neonatal seizures.

    PubMed

    Ni, Hong; Zhao, Dong-Jing; Tian, Tian

    2016-02-01

    Because the ketogenic diet (KD) was affecting expression of energy metabolism- related genes in hippocampus and because lipid membrane peroxidation and its associated autophagy stress were also found to be involved in energy depletion, we hypothesized that KD might exert its neuroprotective action via lipid membrane peroxidation and autophagic signaling. Here, we tested this hypothesis by examining the long-term expression of lipid membrane peroxidation-related cPLA2 and clusterin, its downstream autophagy marker Beclin-1, LC3 and p62, as well as its execution molecule Cathepsin-E following neonatal seizures and chronic KD treatment. On postnatal day 9 (P9), 48 Sprague-Dawley rats were randomly assigned to two groups: flurothyl-induced recurrent seizures group and control group. On P28, they were further randomly divided into the seizure group without ketogenic diet (RS+ND), seizure plus ketogenic diet (RS+KD), the control group without ketogenic diet (NS+ND), and the control plus ketogenic diet (NS+KD). Morris water maze test was performed during P37-P43. Then mossy fiber sprouting and the protein levels were detected by Timm staining and Western blot analysis, respectively. Flurothyl-induced RS+ND rats show a long-term lower amount of cPLA2 and LC3II/I, and higher amount of clusterin, Beclin-1, p62 and Cathepsin-E which are in parallel with hippocampal mossy fiber sprouting and cognitive deficits. Furthermore, chronic KD treatment (RS+KD) is effective in restoring these molecular, neuropathological and cognitive changes. The results imply that a lipid membrane peroxidation and autophagy-associated pathway is involved in the aberrant hippocampal mossy fiber sprouting and cognitive deficits following neonatal seizures, which might be a potential target of KD for the treatment of neonatal seizure-induced brain damage. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Resistance to excitotoxin-induced seizures and neuronal death in mice lacking the preprotachykinin A gene.

    PubMed

    Liu, H; Cao, Y; Basbaum, A I; Mazarati, A M; Sankar, R; Wasterlain, C G

    1999-10-12

    Epileptic seizures are associated with increases in hippocampal excitability, but the mechanisms that render the hippocampus hyperexcitable chronically (in epilepsy) or acutely (in status epilepticus) are poorly understood. Recent evidence suggests that substance P (SP), a peptide that has been implicated in cardiovascular function, inflammatory responses, and nociception, also contributes to hippocampal excitability and status epilepticus, in part by enhancing glutamate release. Here we report that mice with disruption of the preprotachykinin A gene, which encodes SP and neurokinin A, are resistant to kainate excitoxicity. The mice show a reduction in the duration and severity of seizures induced by kainate or pentylenetetrazole, and both necrosis and apoptosis of hippocampal neurons are prevented. Although kainate induced the expression of bax and caspase 3 in the hippocampus of wild-type mice, these critical intracellular mediators of cell death pathways were not altered by kainate injection in the mutant mice. These results indicate that the reduction of seizure activity and the neuroprotection observed in preprotachykinin A null mice are caused by the extinction of a SP/neurokinin A-mediated signaling pathway that is activated by seizures. They suggest that these neurokinins are critical to the control of hippocampal excitability, hippocampal seizures, and hippocampal vulnerability.

  17. Comparative sensitivity of quantitative EEG (QEEG) spectrograms for detecting seizure subtypes.

    PubMed

    Goenka, Ajay; Boro, Alexis; Yozawitz, Elissa

    2018-02-01

    To assess the sensitivity of Persyst version 12 QEEG spectrograms to detect focal, focal with secondarily generalized, and generalized onset seizures. A cohort of 562 seizures from 58 patients was analyzed. Successive recordings with 2 or more seizures during continuous EEG monitoring for clinical indications in the ICU or EMU between July 2016 and January 2017 were included. Patient ages ranged from 5 to 64 years (mean = 36 years). There were 125 focal seizures, 187 secondarily generalized and 250 generalized seizures from 58 patients analyzed. Seizures were identified and classified independently by two epileptologists. A correlate to the seizure pattern in the raw EEG was sought in the QEEG spectrograms in 4-6 h EEG epochs surrounding the identified seizures. A given spectrogram was interpreted as indicating a seizure, if at the time of a seizure it showed a visually significant departure from the pre-event baseline. Sensitivities for seizure detection using each spectrogram were determined for each seizure subtype. Overall sensitivities of the QEEG spectrograms for detecting seizures ranged from 43% to 72%, with highest sensitivity (402/562,72%) by the seizure detection trend. The asymmetry spectrogram had the highest sensitivity for detecting focal seizures (117/125,94%). The FFT spectrogram was most sensitive for detecting secondarily generalized seizures (158/187, 84%). The seizure detection trend was the most sensitive for generalized onset seizures (197/250,79%). Our study suggests that different seizure types have specific patterns in the Persyst QEEG spectrograms. Identifying these patterns in the EEG can significantly increase the sensitivity for seizure identification. Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  18. Behaviors induced or disrupted by complex partial seizures.

    PubMed

    Leung, L S; Ma, J; McLachlan, R S

    2000-09-01

    We reviewed the neural mechanisms underlying some postictal behaviors that are induced or disrupted by temporal lobe seizures in humans and animals. It is proposed that the psychomotor behaviors and automatisms induced by temporal lobe seizures are mediated by the nucleus accumbens. A non-convulsive hippocampal afterdischarge in rats induced an increase in locomotor activity, which was suppressed by the injection of dopamine D(2) receptor antagonist in the nucleus accumbens, and blocked by inactivation of the medial septum. In contrast, a convulsive hippocampal or amygdala seizure induced behavioral hypoactivity, perhaps by the spread of the seizure into the frontal cortex and opiate-mediated postictal depression. Mechanisms underlying postictal psychosis, memory disruption and other long-term behavioral alterations after temporal lobe seizures, are discussed. In conclusion, many of the changes of postictal behaviors observed after temporal lobe seizures in humans may be found in animals, and the basis of the behavioral change may be explained as a change in neural processing in the temporal lobe and the connecting subcortical structures.

  19. Focal CA3 hippocampal subfield atrophy following LGI1 VGKC-complex antibody limbic encephalitis.

    PubMed

    Miller, Thomas D; Chong, Trevor T-J; Aimola Davies, Anne M; Ng, Tammy W C; Johnson, Michael R; Irani, Sarosh R; Vincent, Angela; Husain, Masud; Jacob, Saiju; Maddison, Paul; Kennard, Christopher; Gowland, Penny A; Rosenthal, Clive R

    2017-05-01

    Magnetic resonance imaging has linked chronic voltage-gated potassium channel (VGKC) complex antibody-mediated limbic encephalitis with generalized hippocampal atrophy. However, autoantibodies bind to specific rodent hippocampal subfields. Here, human hippocampal subfield (subiculum, cornu ammonis 1-3, and dentate gyrus) targets of immunomodulation-treated LGI1 VGKC-complex antibody-mediated limbic encephalitis were investigated using in vivo ultra-high resolution (0.39 × 0.39 × 1.0 mm3) 7.0 T magnetic resonance imaging [n = 18 patients, 17 patients (94%) positive for LGI1 antibody and one patient negative for LGI1/CASPR2 but positive for VGKC-complex antibodies, mean age: 64.0 ± 2.55 years, median 4 years post-limbic encephalitis onset; n = 18 controls]. First, hippocampal subfield quantitative morphometry indicated significant volume loss confined to bilateral CA3 [F(1,34) = 16.87, P < 0.0001], despite hyperintense signal evident in 5 of 18 patients on presentation. Second, early and later intervention (<3 versus >3 months from symptom onset) were associated with CA3 atrophy. Third, whole-brain voxel-by-voxel morphometry revealed no significant grey matter loss. Fourth, CA3 subfield atrophy was associated with severe episodic but not semantic amnesia for postmorbid autobiographical events that was predicted by variability in CA3 volume. The results raise important questions about the links with histopathology, the impact of the observed focal atrophy on other CA3-mediated reconstructive and episodic mechanisms, and the role of potential antibody-mediated pathogenicity as part of the pathophysiology cascade in humans. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

  20. Focal Electrically Administered Seizure Therapy (FEAST): A novel form of ECT illustrates the roles of current directionality, polarity, and electrode configuration in seizure induction

    PubMed Central

    Spellman, Timothy; Peterchev, Angel V.; Lisanby, Sarah H.

    2009-01-01

    Electroconvulsive therapy (ECT) is a mainstay in the treatment of severe, medication resistant depression. The antidepressant efficacy and cognitive side effects of ECT are influenced by the position of the electrodes on the head and by the degree to which the electrical stimulus exceeds the threshold for seizure induction. However, surprisingly little is known about the effects of other key electrical parameters such as current directionality, polarity, and electrode configuration. Understanding these relationships may inform the optimization of therapeutic interventions to improve their risk/benefit ratio. To elucidate these relationships, we evaluated a novel form of ECT (focal electrically administered seizure therapy, FEAST) that combines unidirectional stimulation, control of polarity, and an asymmetrical electrode configuration, and contrasted it with conventional ECT in a nonhuman primate model. Rhesus monkeys had their seizure thresholds determined on separate days with ECT conditions that crossed the factors of current directionality (unidirectional or bidirectional), electrode configuration (standard bilateral or FEAST (small anterior and large posterior electrode)), and polarity (assignment of anode and cathode in unidirectional stimulation). Ictal expression and post-ictal suppression were quantified via scalp EEG. Findings were replicated and extended in a second experiment with the same subjects. Seizures were induced in each of 75 trials, including 42 FEAST procedures. Seizure thresholds were lower with unidirectional than with bidirectional stimulation (p<0.0001), and lower in FEAST than in bilateral ECS (p=0.0294). Ictal power was greatest in posterior-anode unidirectional FEAST, and post-ictal suppression was strongest in anterior-anode FEAST (p=0.0008 and p=0.0024, respectively). EEG power was higher in the stimulated hemisphere in posterior-anode FEAST (p=0.0246), consistent with the anode being the site of strongest activation. These findings

  1. Effects of transcranial focal electrical stimulation via tripolar concentric ring electrodes on pentylenetetrazole-induced seizures in rats

    PubMed Central

    Besio, W.G.; Makeyev, O.; Medvedev, A.; Gale, K.

    2013-01-01

    Purpose To study the effects of noninvasive transcranial focal electrical stimulation (TFS) via tripolar concentric ring electrodes (TCRE) on the electrographic and behavioral activity from pentylenetetrazole (PTZ)-induced seizures in rats. Methods The TCREs were attached to the rat scalp. PTZ was administered and, after the first myoclonic jerk was observed, TFS was applied to the TFS treated group. The electroencephalogram (EEG) and behavioral activity were recorded and studied. Results In the case of the TFS treated group, after TFS, there was a significant (p = 0.001) decrease in power compared to the control group in delta, theta, and alpha frequency bands. The number of myoclonic jerks was significantly different (p = 0.002) with median of 22 and 4.5 for the control group and the TFS treated groups, respectively. The duration of myoclonic activity was also significantly different (p= 0.031) with median of 17.56 min for the control group versus 8.63 min for the TFS treated group. At the same time there was no significant difference in seizure onset latency and maximal behavioral seizure activity score between control and TFS treated groups. Conclusions TFS via TCREs interrupted PTZ-induced seizures and electrographic activity was reduced towards the “baseline.” The significantly reduced electrographic power, number of myoclonic jerks, and duration of myoclonic activity of PTZ-induced seizures suggests that TFS may have an anticonvulsant effect. PMID:23290195

  2. Effects of transcranial focal electrical stimulation via tripolar concentric ring electrodes on pentylenetetrazole-induced seizures in rats.

    PubMed

    Besio, W G; Makeyev, O; Medvedev, A; Gale, K

    2013-07-01

    To study the effects of noninvasive transcranial focal electrical stimulation (TFS) via tripolar concentric ring electrodes (TCRE) on the electrographic and behavioral activity from pentylenetetrazole (PTZ)-induced seizures in rats. The TCREs were attached to the rat scalp. PTZ was administered and, after the first myoclonic jerk was observed, TFS was applied to the TFS treated group. The electroencephalogram (EEG) and behavioral activity were recorded and studied. In the case of the TFS treated group, after TFS, there was a significant (p=0.001) decrease in power compared to the control group in delta, theta, and alpha frequency bands. The number of myoclonic jerks was significantly different (p=0.002) with median of 22 and 4.5 for the control group and the TFS treated groups, respectively. The duration of myoclonic activity was also significantly different (p=0.031) with median of 17.56 min for the control group versus 8.63 min for the TFS treated group. At the same time there was no significant difference in seizure onset latency and maximal behavioral seizure activity score between control and TFS treated groups. TFS via TCREs interrupted PTZ-induced seizures and electrographic activity was reduced toward the "baseline." The significantly reduced electrographic power, number of myoclonic jerks, and duration of myoclonic activity of PTZ-induced seizures suggests that TFS may have an anticonvulsant effect. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. Long-term consequences of a prolonged febrile seizure in a dual pathology model.

    PubMed

    Gibbs, Steve; Chattopadhyaya, Bidisha; Desgent, Sébastien; Awad, Patricia N; Clerk-Lamalice, Olivier; Levesque, Maxime; Vianna, Rose-Mari; Rébillard, Rose-Marie; Delsemme, Andrée-Anne; Hébert, David; Tremblay, Luc; Lepage, Martin; Descarries, Laurent; Di Cristo, Graziella; Carmant, Lionel

    2011-08-01

    Clinical evidence suggests that febrile status epilepticus (SE) in children can lead to acute hippocampal injury and subsequent temporal lobe epilepsy. The contribution of febrile SE to the mechanisms underlying temporal lobe epilepsy are however poorly understood. A rat model of temporal lobe epilepsy following hyperthermic SE was previously established in our laboratory, wherein a focal cortical lesion induced at postnatal day 1 (P1), followed by a hyperthermic SE (more than 30 min) at P10, leads to hippocampal atrophy at P22 (dual pathology model) and spontaneous recurrent seizures (SRS) with mild visuospatial memory deficits in adult rats. The goal of this study was to identify the long term electrophysiological, anatomical and molecular changes in this model. Following hyperthermic SE, all cortically lesioned pups developed progressive SRS as adults, characterized by the onset of highly rhythmic activity in the hippocampus. A reduction of hippocampal volume on the side of the lesion preceded the SRS and was associated with a loss of hippocampal neurons, a marked decrease in pyramidal cell spine density, an increase in the hippocampal levels of NMDA receptor NR2A subunit, but no significant change in GABA receptors. These findings suggest that febrile SE in the abnormal brain leads to hippocampal injury that is followed by progressive network reorganization and molecular changes that contribute to the epileptogenesis as well as the observed memory deficits. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Multichannel continuous electroencephalography-functional near-infrared spectroscopy recording of focal seizures and interictal epileptiform discharges in human epilepsy: a review

    PubMed Central

    Peng, Ke; Pouliot, Philippe; Lesage, Frédéric; Nguyen, Dang Khoa

    2016-01-01

    Abstract. Functional near-infrared spectroscopy (fNIRS) has emerged as a promising neuroimaging technique as it allows noninvasive and long-term monitoring of cortical hemodynamics. Recent work by our group and others has revealed the potential of fNIRS, combined with electroencephalography (EEG), in the context of human epilepsy. Hemodynamic brain responses attributed to epileptic events, such as seizures and interictal epileptiform discharges (IEDs), are routinely observed with a good degree of statistical significance and in concordance with clinical presentation. Recording done with over 100 channels allows sufficiently large coverage of the epileptic focus and other areas. Three types of seizures have been documented: frontal lobe seizures, temporal lobe seizures, and posterior seizures. Increased oxygenation was observed in the epileptic focus in most cases, while rapid but similar hemodynamic variations were identified in the contralateral homologous region. While investigating IEDs, it was shown that their hemodynamic effect is observable with fNIRS, that their response is associated with significant (inhibitive) nonlinearities, and that the sensitivity and specificity of fNIRS to localize the epileptic focus can be estimated in a sample of 40 patients. This paper first reviews recent EEG-fNIRS developments in epilepsy research and then describes applications to the study of focal seizures and IEDs. PMID:26958576

  5. Hippocampal subfield segmentation in temporal lobe epilepsy: Relation to outcomes.

    PubMed

    Kreilkamp, B A K; Weber, B; Elkommos, S B; Richardson, M P; Keller, S S

    2018-06-01

    To investigate the clinical and surgical outcome correlates of preoperative hippocampal subfield volumes in patients with refractory temporal lobe epilepsy (TLE) using a new magnetic resonance imaging (MRI) multisequence segmentation technique. We recruited 106 patients with TLE and hippocampal sclerosis (HS) who underwent conventional T1-weighted and T2 short TI inversion recovery MRI. An automated hippocampal segmentation algorithm was used to identify twelve subfields in each hippocampus. A total of 76 patients underwent amygdalohippocampectomy and postoperative seizure outcome assessment using the standardized ILAE classification. Semiquantitative hippocampal internal architecture (HIA) ratings were correlated with hippocampal subfield volumes. Patients with left TLE had smaller volumes of the contralateral presubiculum and hippocampus-amygdala transition area compared to those with right TLE. Patients with right TLE had reduced contralateral hippocampal tail volumes and improved outcomes. In all patients, there were no significant relationships between hippocampal subfield volumes and clinical variables such as duration and age at onset of epilepsy. There were no significant differences in any hippocampal subfield volumes between patients who were rendered seizure free and those with persistent postoperative seizure symptoms. Ipsilateral but not contralateral HIA ratings were significantly correlated with gross hippocampal and subfield volumes. Our results suggest that ipsilateral hippocampal subfield volumes are not related to the chronicity/severity of TLE. We did not find any hippocampal subfield volume or HIA rating differences in patients with optimal and unfavorable outcomes. In patients with TLE and HS, sophisticated analysis of hippocampal architecture on MRI may have limited value for prediction of postoperative outcome. © 2018 The Authors. Acta Neurologica Scandinavica Published by John Wiley & Sons Ltd.

  6. Inheritance of Febrile Seizures in Sudden Unexplained Death in Toddlers

    PubMed Central

    Holm, Ingrid A.; Poduri, Annapurna; Crandall, Laura; Haas, Elisabeth; Grafe, Marjorie R.; Kinney, Hannah C.; Krous, Henry F.

    2014-01-01

    Sudden unexplained death in toddlers has been associated with febrile seizures, family history of febrile seizures, and hippocampal anomalies. We investigated the mode of inheritance for febrile seizures in these families. A three-generation pedigree was obtained from families enrolled in the San Diego Sudden Unexplained Death in Childhood Research Project, involving toddlers with sudden unexplained death, febrile seizures, and family history of febrile seizures. In our six cases, death was unwitnessed and related to sleep. The interval from last witnessed febrile seizure to death ranged from 3 weeks to 6 months. Hippocampal abnormalities were identified in one of three cases with available autopsy sections. Autosomal dominant inheritance of febrile seizures was observed in three families. A fourth demonstrated autosomal dominant inheritance with incomplete penetrance or variable expressivity. In two families, the maternal and paternal sides manifested febrile seizures. In this series, the major pattern of inheritance in toddlers with sudden unexplained death and febrile seizures was autosomal dominant. Future studies should develop markers (including genetic) to identify which patients with febrile seizures are at risk for sudden unexplained death in childhood, and to provide guidance for families and physicians. PMID:22490769

  7. Hippocampal volume and memory performance in children with perinatal stroke.

    PubMed

    Gold, Jeffrey J; Trauner, Doris A

    2014-01-01

    Pediatric neurologists and neonatologists often are asked to predict cognitive outcome after perinatal brain injury (including likely memory and learning outcomes). However, relatively few data exist on how accurate predictions can be made. Furthermore, although the consequences of brain injury on hippocampal volume and memory performance have been studied extensively in adults, little work has been done in children. We measured the volume of the hippocampus in 27 children with perinatal stroke and 19 controls, and measured their performance on standardized verbal and non-verbal memory tests. We discovered the following: (1) As a group, children with perinatal stroke had smaller left and right hippocampi compared with control children. (2) Individually, children with perinatal stroke demonstrated 1 of 3 findings: no hippocampal loss, unilateral hippocampal loss, or bilateral hippocampal volume loss compared with control children. (3) Hippocampal volume inversely correlated with memory test performance in the perinatal stroke group, with smaller left and right hippocampal volumes related to poorer verbal and non-verbal memory test performance, respectively. (4) Seizures played a significant role in determining memory deficit and extent of hippocampal volume reduction in patients with perinatal stroke. These findings support the view that, in the developing brain, the left and right hippocampi preferentially support verbal and nonverbal memory respectively, a consistent finding in the adult literature but a subject of debate in the pediatric literature. This is the first work to report that children with focal brain injury incurred from perinatal stroke have volume reduction in the hippocampus and impairments in certain aspects of declarative memory. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Temporal pole abnormalities in temporal lobe epilepsy with hippocampal sclerosis: Clinical significance and seizure outcome after surgery.

    PubMed

    Di Gennaro, Giancarlo; D'Aniello, Alfredo; De Risi, Marco; Grillea, Giovanni; Quarato, Pier Paolo; Mascia, Addolorata; Grammaldo, Liliana G; Casciato, Sara; Morace, Roberta; Esposito, Vincenzo; Picardi, Angelo

    2015-11-01

    To assess the clinical significance of temporal pole abnormalities (temporopolar blurring, TB, and temporopolar atrophy, TA) in patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS) with a long post-surgical follow-up. We studied 60 consecutive patients with TLE-HS and 1.5 preoperative MRI scans who underwent surgery and were followed up for at least 5 years (mean follow-up 7.3 years). Based on findings of pre-surgical MRI, patients were classified according to the presence of TB or TA. Groups were compared on demographic, clinical, neuropsychological data, and seizure outcome. TB was found in 37 (62%) patients, while TA was found in 35 (58%) patients, always ipsilateral to HS, with a high degree of overlap (83%) between TB and TA (p<0.001). Patients with TB did not differ from those without TB with regard to history of febrile convulsions, GTCSs, age of epilepsy onset, side of surgery, seizure frequency, seizure outcome, and neuropsychological outcome. On the other hand, they were significantly older, had a longer duration of epilepsy, and displayed lower preoperative scores on several neuropsychological tests. Similar findings were observed for TA. Multivariate analysis corroborated the association between temporopolar abnormalities and age at onset, age at surgery (for TB only), and lower preoperative scores on some neuropsychological tests. Temporopolar abnormalities are frequent in patients with TLE-HS. Our data support the hypothesis that TB and TA are caused by seizure-related damages. These abnormalities did not influence seizure outcome, even after a long-term post-surgical follow-up. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  9. Changes in Hippocampal Volume are Correlated with Cell Loss but Not with Seizure Frequency in Two Chronic Models of Temporal Lobe Epilepsy

    PubMed Central

    Polli, Roberson S.; Malheiros, Jackeline M.; dos Santos, Renan; Hamani, Clement; Longo, Beatriz M.; Tannús, Alberto; Mello, Luiz E.; Covolan, Luciene

    2014-01-01

    Kainic acid (KA) or pilocarpine (PILO) have been used in rats to model human temporal lobe epilepsy (TLE) but the distribution and severity of structural lesions between these two models may differ. Magnetic resonance imaging (MRI) studies have used quantitative measurements of hippocampal T2 (T2HP) relaxation time and volume, but simultaneous comparative results have not been reported yet. The aim of this study was to compare the MRI T2HP and volume with histological data and frequency of seizures in both models. KA- and PILO-treated rats were imaged with a 2 T MRI scanner. T2HP and volume values were correlated with the number of cells, mossy fiber sprouting, and spontaneous recurrent seizures (SRS) frequency over the 9 months following status epilepticus (SE). Compared to controls, KA-treated rats had unaltered T2HP, pronounced reduction in hippocampal volume and concomitant cell reduction in granule cell layer, CA1 and CA3 at 3 months post SE. In contrast, hippocampal volume was unchanged in PILO-treated animals despite detectable increased T2HP and cell loss in granule cell layer, CA1 and CA3. In the following 6 months, MRI hippocampal volume remained stable with increase of T2HP signal in the KA-treated group. The number of CA1 and CA3 cells was smaller than age-matched CTL group. In contrast, PILO group had MRI volumetric reduction accompanied by reduction in the number of CA1 and CA3 cells. In this group, T2HP signal was unaltered at 6 or 9 months after status. Reductions in the number of cells were not progressive in both models. Notably, the SRS frequency was higher in PILO than in the KA model. The volumetry data correlated well with tissue damage in the epileptic brain, suggesting that MRI may be useful for tracking longitudinal hippocampal changes, allowing the assessment of individual variability and disease progression. Our results indicate that the temporal changes in hippocampal morphology are distinct for both models of TLE and that

  10. Intraoperative Magnetic-Resonance Tomography and Neuronavigation During Resection of Focal Cortical Dysplasia Type II in Adult Epilepsy Surgery Offers Better Seizure Outcomes.

    PubMed

    Roessler, Karl; Kasper, Burkhard S; Heynold, Elisabeth; Coras, Roland; Sommer, Björn; Rampp, Stefan; Hamer, Hajo M; Blümcke, Ingmar; Buchfelder, Michael

    2018-01-01

    Focal cortical dysplasia (FCD) is one important cause of drug-resistant epilepsy potentially curable by epilepsy surgery. We investigated the options of using neuronavigation and intraoperative magnetic-resonance tomographical imaging (MRI) to avoid residual epileptogenic tissue during resection of patients with FCD II to improve seizure outcome. Altogether, 24 patients with FCD II diagnosed by MRI (16 female, 8 male; mean age 34 ± 10 years) suffered from drug-resistant electroclinical and focal epilepsy for a mean of 20.7 ± 5 years. Surgery was performed with preoperative stereoelectroencephalography (in 15 patients), neuronavigation, and intraoperative 1.5T-iopMRI in all 24 investigated patients. In 75% of patients (18/24), a complete resection was performed. In 89% (16/18) of completely resected patients, we documented an Engel I seizure outcome after a mean follow-up of 42 months. All incompletely resected patients had a worse outcome (Engel II-III, P < 0.0002). Patients with FCD IIB had also significant better seizure outcome compared with patients diagnosed as having FCD IIA (82% vs. 28%, P < 0.02). In 46% (11/24) of patients, intraoperative second-look surgeries due to residual lesions detected during the intraoperative MRI were performed. In these 11 patients, there were significant more completely seizure free patients (73% vs. 38% Engel IA), compared with 13 patients who finished surgery after the first intraoperative MRI (P < 0.05). Excellent seizure outcome after surgery of patients with FCD II positively correlated with the amount of resection, histologic subtype, and the use of intraoperative MRI, especially when intraoperative second-look surgeries were performed. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Bursts of seizures in long-term recordings of human focal epilepsy

    PubMed Central

    Karoly, Philippa J.; Nurse, Ewan S.; Freestone, Dean R.; Ung, Hoameng; Cook, Mark J.; Boston, Ray

    2017-01-01

    Summary Objective We report on temporally clustered seizures detected from continuous long-term ambulatory human electroencephalographic data. The objective was to investigate short-term seizure clustering, which we have termed bursting, and consider implications for patient care, seizure prediction, and evaluating therapies. Methods Chronic ambulatory intracranial EEG data collected for the purpose of seizure prediction were annotated to identify seizure events. A detection algorithm was used to identify bursts of events. Burst events were compared to non-burst events to evaluate event dispersion, duration and dynamics. Results Bursts of seizures were present in six of fifteen patients, and detections were consistent over long term monitoring (> 2 years). Seizures within bursts are highly overdispersed compared to non-burst seizures. There was a complicated relationship between bursts and clinical seizures, although bursts were associated with multi-modal distributions of seizure duration, and poorer predictive outcomes. For three subjects, bursts demonstrated distinctive pre-ictal dynamics compared to clinical seizures. Significance We have previously hypothesized that there are distinct physiological pathways underlying short and long duration seizures. Here we show that burst seizures fall almost exclusively within the short population of seizure durations; however, a short duration was not sufficient to induce or imply bursting. We can therefore conclude that in addition to distinct mechanisms underlying seizure duration, there are separate factors regulating bursts of seizures. We show that bursts were a robust phenomenon in our patient cohort, which were consistent with overdispersed seizure rates, suggesting long-memory dynamics. PMID:28084639

  12. Rosiglitazone Suppresses In Vitro Seizures in Hippocampal Slice by Inhibiting Presynaptic Glutamate Release in a Model of Temporal Lobe Epilepsy.

    PubMed

    Wong, Shi-Bing; Cheng, Sin-Jhong; Hung, Wei-Chen; Lee, Wang-Tso; Min, Ming-Yuan

    2015-01-01

    Peroxisomal proliferator-activated receptor gamma (PPARγ) is a nuclear hormone receptor whose agonist, rosiglitazone has a neuroprotective effect to hippocampal neurons in pilocarpine-induced seizures. Hippocampal slice preparations treated in Mg2+ free medium can induce ictal and interictal-like epileptiform discharges, which is regarded as an in vitro model of N-methyl-D-aspartate (NMDA) receptor-mediated temporal lobe epilepsy (TLE). We applied rosiglitazone in hippocampal slices treated in Mg2+ free medium. The effects of rosiglitazone on hippocampal CA1-Schaffer collateral synaptic transmission were tested. We also examined the neuroprotective effect of rosiglitazone toward NMDA excitotoxicity on cultured hippocampal slices. Application of 10 μM rosiglitazone significantly suppressed amplitude and frequency of epileptiform discharges in CA1 neurons. Pretreatment with the PPARγ antagonist GW9662 did not block the effect of rosiglitazone on suppressing discharge frequency, but reverse the effect on suppressing discharge amplitude. Application of rosiglitazone suppressed synaptic transmission in the CA1-Schaffer collateral pathway. By miniature excitatory-potential synaptic current (mEPSC) analysis, rosiglitazone significantly suppressed presynaptic neurotransmitter release. This phenomenon can be reversed by pretreating PPARγ antagonist GW9662. Also, rosiglitazone protected cultured hippocampal slices from NMDA-induced excitotoxicity. The protective effect of 10 μM rosiglitazone was partially antagonized by concomitant high dose GW9662 treatment, indicating that this effect is partially mediated by PPARγ receptors. In conclusion, rosiglitazone suppressed NMDA receptor-mediated epileptiform discharges by inhibition of presynaptic neurotransmitter release. Rosiglitazone protected hippocampal slice from NMDA excitotoxicity partially by PPARγ activation. We suggest that rosiglitazone could be a potential agent to treat patients with TLE.

  13. Interference of TRPV1 function altered the susceptibility of PTZ-induced seizures.

    PubMed

    Jia, Yun-Fang; Li, Ying-Chao; Tang, Yan-Ping; Cao, Jun; Wang, Li-Ping; Yang, Yue-Xiong; Xu, Lin; Mao, Rong-Rong

    2015-01-01

    Transient receptor potential vanilloid 1 (TRPV1) is widely distributed in the central nervous system (CNS) including hippocampus, and regulates the balance of excitation and inhibition in CNS, which imply its important role in epilepsy. We used both pharmacological manipulations and transgenic mice to disturb the function of TRPV1 and then studied the effects of these alterations on the susceptibility of pentylenetetrazol (PTZ)-induced seizures. Our results showed that systemic administration of TRPV1 agonist capsaicin (CAP, 40 mg/kg) directly induced tonic-clonic seizures (TCS) without PTZ induction. The severity of seizure was increased in lower doses of CAP groups (5 and 10 mg/kg), although the latency to TCS was delayed. On the other hand, systemic administration of TRPV1 antagonist capsazepine (CPZ, 0.05 and 0.5 mg/kg) and TRPV1 knockout mice exhibited delayed latency to TCS and reduced mortality. Furthermore, hippocampal administration of CPZ (10 and 33 nmol/μL/side) was firstly reported to increase the latency to TCS, decrease the maximal grade of seizure and mortality. It is worth noting that decreased susceptibility of PTZ-induced seizures was observed in hippocampal TRPV1 overexpression mice and hippocampal CAP administration (33 nmol/μL/side), which is opposite from results of systemic agonist CAP. Our findings suggest that the systemic administration of TRPV1 antagonist may be a novel therapeutic target for epilepsy, and alteration of hippocampal TRPV1 function exerts a critical role in seizure susceptibility.

  14. New directions in the rational design of electrical and magnetic seizure therapies: individualized Low Amplitude Seizure Therapy (iLAST) and Magnetic Seizure Therapy (MST).

    PubMed

    Radman, Thomas; Lisanby, Sarah H

    2017-04-01

    Electroconvulsive therapy remains a key treatment option for severe cases of depression, but undesirable side-effects continue to limit its use. Innovations in the design of novel seizure therapies seek to improve its risk benefit ratio through enhanced control of the focality of stimulation. The design of seizure therapies with increased spatial precision is motivated by avoiding stimulation of deep brain structures implicated in memory retention, including the hippocampus. The development of two innovations in seizure therapy-individualized low-amplitude seizure therapy (iLAST) and magnetic seizure therapy (MST), are detailed. iLAST is a method of seizure titration involving reducing current spread in the brain by titrating current amplitude from the traditional fixed amplitudes. MST, which can be used in conjunction with iLAST dosing methods, involves the use of magnetic stimulation to reduce shunting and spreading of current by the scalp occurring during electrical stimulation. Evidence is presented on the rationale for increasing the focality of ECT in hopes of preserving its effectiveness, while reducing cognitive side-effects. Finally, the value of electric field and neural modelling is illustrated to explain observed clinical effects of modifications to ECT technique, and their utility in the rational design of the next generation of seizure therapies.

  15. Remote infarct of the temporal lobe with coexistent hippocampal sclerosis in mesial temporal lobe epilepsy.

    PubMed

    Gales, Jordan M; Prayson, Richard A

    2016-02-01

    In patients undergoing surgery for temporal lobe epilepsy, hippocampal sclerosis remains the most commonly observed pathology. In addition to hippocampal sclerosis, 5% to 30% of these resections on magnetic resonance imaging contain a second independently epileptogenic lesion, commonly referred to as dual pathology. A second etiology of seizure activity, as seen in dual pathology, may serve as an important cause of treatment failure in striving for post-operative seizure control. Dual pathology, consisting of hippocampal sclerosis and a remote infarct of the adjacent cortex, has been rarely reported. Cases of pathologically confirmed hippocampal sclerosis diagnosed between January 2000 and December 2012 (n = 349) were reviewed, and 7 cases of coexistent infarct (2%) formed the study group. Seven individuals (mean age, 29years; range, 5-47 years) with a mean epilepsy duration of 12.5years (3.3-25 years) and a mean pre-surgery frequency of 15 seizures per week (range, 0.5-56 seizures/week) were followed up postoperatively for a mean duration of 64months (range, 3-137 months). Pathologically, the most common form of hippocampal sclerosis observed was International League against Epilepsy type Ib or severe variant (n = 4). Four of the six individuals with post-surgery follow-up were seizure free at last encounter. The reported incidence of dual pathology, including hippocampal sclerosis and remote infarct, is low (2% in the present study) but may indicate a slightly increased risk of developing hippocampal sclerosis in the setting of a remote infarct. Surgical intervention for such cases anecdotally appears effective in achieving seizure control. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Interactive effects of prenatal exposure to restraint stress and alcohol on pentylenetetrazol-induced seizure behaviors in rat offspring.

    PubMed

    Hashemi, Paria; Roshan-Milani, Shiva; Saboory, Ehsan; Ebrahimi, Loghman; Soltanineghad, Maryam

    2016-11-01

    Prenatal exposure to stress or alcohol increases vulnerability of brain regions involved in neurobehavioral development and programs susceptibility to seizure. To examine how prenatal alcohol interferes with stress-sensitive seizures, corticosterone (COS) blood levels and pentylenetetrazol (PTZ)-induced seizure behaviors were investigated in rat pups, prenatally exposed to stress, alcohol, or both. Pregnant rats were exposed to stress and saline/alcohol on 17, 18, and 19 days of pregnancy and divided into four groups of control-saline (CS), control-alcohol (CA), restraint stress-saline (RS), and restraint stress-alcohol (RA). In CS/CA groups, rats received saline/alcohol (20%, 2 g/kg, intraperitoneally [i.p.]). In RS/RA groups, rats were exposed to restraint stress by being held immobile in a Plexiglas ® tube (twice/day, 1 h/session), and received saline/alcohol, simultaneously. After parturition, on postnatal days 6 and 15 (P6 & P15), blood samples were collected from the pups to determine COS level. On P15 and P25, PTZ (45 mg/kg) was injected into the rest of the pups and seizure behaviors were then recorded. COS levels increased in pups of the RS group but not in pups of the RA group. Both focal and tonic-clonic seizures were prevalent and severe in pups of the RS group, whereas only focal seizures were prominent in pups of the CA group. However, pups prenatally exposed to co-administration of alcohol and stress, unexpectedly, did not show additive epileptic effects. The failure of pups prenatally exposed to alcohol to show progressive or facilitatory epileptic responses to stressors, indicates decreased plasticity and adaptability, which may negatively affect HPA-axis performance or hippocampal structure/function. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Focal epilepsy recruiting a generalised network of juvenile myoclonic epilepsy: a case report.

    PubMed

    Khaing, Myo; Lim, Kheng-Seang; Tan, Chong-Tin

    2014-09-01

    We report a patient with juvenile myoclonic epilepsy who subsequently developed temporal lobe epilepsy, which gradually became clinically dominant. Video telemetry revealed both myoclonic seizures and temporal lobe seizures. The temporal lobe seizures were accompanied by a focal recruiting rhythm with rapid generalisation on EEG, in which the ictal EEG pattern during the secondary generalised phase was morphologically similar to the ictal pattern during myoclonic seizures. The secondary generalised seizures of the focal epilepsy responded to sodium valproate, similar to the myoclonic epilepsy. In this rare case of coexistent Juvenile Myoclonic Epilepsy and Temporal lobe epilepsy, the possibility of focal epilepsy recruiting a generalised epileptic network was proposed and discussed.

  18. MicroRNA-34a upregulation during seizure-induced neuronal death

    PubMed Central

    Sano, T; Reynolds, J P; Jimenez-Mateos, E M; Matsushima, S; Taki, W; Henshall, D C

    2012-01-01

    MicroRNAs (miRNAs) are short, noncoding RNAs that function as posttranscriptional regulators of gene expression by controlling translation of mRNAs. A subset of miRNAs may be critical for the control of cell death, including the p53-regulated miRNA, miR-34a. Because seizures activate p53, and p53-deficient mice are reportedly resistant to damage caused by prolonged seizures, we investigated the role of miR-34a in seizure-induced neuronal death in vivo. Status epilepticus was induced by intra-amygdala microinjection of kainic acid in mice. This led to an early (2 h) multifold upregulation of miR-34a in the CA3 and CA1 hippocampal subfields and lower protein levels of mitogen-activated kinase kinase kinase 9, a validated miR-34a target. Immunoprecipitation of the RNA-induced silencing complex component, Argonaute-2, eluted significantly higher levels of miR-34a after seizures. Injection of mice with pifithrin-α, a putative p53 inhibitor, prevented miR-34a upregulation after seizures. Intracerebroventricular injection of antagomirs targeting miR-34a reduced hippocampal miR-34a levels and had a small modulatory effect on apoptosis-associated signaling, but did not prevent hippocampal neuronal death in models of either severe or moderate severity status epilepticus. Thus, prolonged seizures cause subfield-specific, temporally restricted upregulation of miR-34a, which may be p53 dependent, but miR-34a is probably not important for seizure-induced neuronal death in this model. PMID:22436728

  19. Verbal learning and memory outcome in selective amygdalohippocampectomy versus temporal lobe resection in patients with hippocampal sclerosis.

    PubMed

    Foged, Mette Thrane; Vinter, Kirsten; Stauning, Louise; Kjær, Troels W; Ozenne, Brice; Beniczky, Sándor; Paulson, Olaf B; Madsen, Flemming Find; Pinborg, Lars H

    2018-02-01

    With the advent of new very selective techniques like thermal laser ablation to treat drug-resistant focal epilepsy, the controversy of resection size in relation to seizure outcome versus cognitive deficits has gained new relevance. The purpose of this study was to test the influence of the selective amygdalohippocampectomy (SAH) versus nonselective temporal lobe resection (TLR) on seizure outcome and cognition in patients with mesial temporal lobe epilepsy (MTLE) and histopathological verified hippocampal sclerosis (HS). We identified 108 adults (>16years) with HS, operated between 1995 and 2009 in Denmark. Exclusion criteria are the following: Intelligence below normal range, right hemisphere dominance, other native languages than Danish, dual pathology, and missing follow-up data. Thus, 56 patients were analyzed. The patients were allocated to SAH (n=22) or TLR (n=34) based on intraoperative electrocorticography. Verbal learning and verbal memory were tested pre- and postsurgery. Seizure outcome did not differ between patients operated using the SAH versus the TLR at 1year (p=0.951) nor at 7years (p=0.177). Verbal learning was more affected in patients resected in the left hemisphere than in the right (p=0.002). In patients with left-sided TLR, a worsening in verbal memory performance was found (p=0.011). Altogether, 73% were seizure-free for 1year and 64% for 7years after surgery. In patients with drug-resistant focal MTLE, HS and no magnetic resonance imaging (MRI) signs of dual pathology, selective amygdalohippocampectomy results in sustained seizure freedom and better memory function compared with patients operated with nonselective temporal lobe resection. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. SRF modulates seizure occurrence, activity induced gene transcription and hippocampal circuit reorganization in the mouse pilocarpine epilepsy model.

    PubMed

    Lösing, Pascal; Niturad, Cristina Elena; Harrer, Merle; Reckendorf, Christopher Meyer Zu; Schatz, Theresa; Sinske, Daniela; Lerche, Holger; Maljevic, Snezana; Knöll, Bernd

    2017-07-17

    A hallmark of temporal lobe epilepsy (TLE) is hippocampal neuronal demise and aberrant mossy fiber sprouting. In addition, unrestrained neuronal activity in TLE patients induces gene expression including immediate early genes (IEGs) such as Fos and Egr1.We employed the mouse pilocarpine model to analyze the transcription factor (TF) serum response factor (SRF) in epileptogenesis, seizure induced histopathology and IEG induction. SRF is a neuronal activity regulated TF stimulating IEG expression as well as nerve fiber growth and guidance. Adult conditional SRF deficient mice (Srf CaMKCreERT2 ) were more refractory to initial status epilepticus (SE) acquisition. Further, SRF deficient mice developed more spontaneous recurrent seizures (SRS). Genome-wide transcriptomic analysis uncovered a requirement of SRF for SE and SRS induced IEG induction (e.g. Fos, Egr1, Arc, Npas4, Btg2, Atf3). SRF was required for epilepsy associated neurodegeneration, mossy fiber sprouting and inflammation. We uncovered MAP kinase signaling as SRF target during epilepsy. Upon SRF ablation, seizure evoked induction of dual specific phosphatases (Dusp5 and Dusp6) was reduced. Lower expression of these negative ERK kinase regulators correlated with altered P-ERK levels in epileptic Srf mutant animals.Overall, this study uncovered an SRF contribution to several processes of epileptogenesis in the pilocarpine model.

  1. Role of Phosphatidylinositol-3 Kinase Pathway in NMDA Preconditioning: Different Mechanisms for Seizures and Hippocampal Neuronal Degeneration Induced by Quinolinic Acid.

    PubMed

    Constantino, Leandra C; Binder, Luisa B; Vandresen-Filho, Samuel; Viola, Giordano G; Ludka, Fabiana K; Lopes, Mark W; Leal, Rodrigo B; Tasca, Carla I

    2018-04-20

    N-methyl D-aspartate (NMDA) preconditioning is evoked by the administration of a subtoxic dose of NMDA and is protective against neuronal excitotoxicity. This effect may involve a diversity of targets and cell signaling cascades associated to neuroprotection. Phosphatidylinositol-3 kinase/protein kinase B (PI3K/Akt) and mitogen-activated protein kinases (MAPKs) such as extracellular regulated protein kinase 1/2 (ERK1/2) and p38 MAPK pathways play a major role in neuroprotective mechanisms. However, their involvement in NMDA preconditioning was not yet fully investigated. The present study aimed to evaluate the effect of NMDA preconditioning on PI3K/Akt, ERK1/2, and p38 MAPK pathways in the hippocampus of mice and characterize the involvement of PI3K on NMDA preconditioning-evoked prevention of seizures and hippocampal cell damage induced by quinolinic acid (QA). Thus, mice received wortmannin (a PI3K inhibitor) and 15 min later a subconvulsant dose of NMDA (preconditioning) or saline. After 24 h of this treatment, an intracerebroventricular QA infusion was administered. Phosphorylation levels and total content of Akt, glycogen synthase protein kinase-3β (GSK-3β), ERK1/2, and p38 MAPK were not altered after 24 h of NMDA preconditioning with or without wortmmanin pretreatment. Moreover, after QA administration, behavioral seizures, hippocampal neuronal degeneration, and Akt activation were evaluated. Inhibition of PI3K pathway was effective in abolishing the protective effect of NMDA preconditioning against QA-induced seizures, but did not modify neuronal protection promoted by preconditioning as evaluated by Fluoro-Jade B staining. The study confirms that PI3K participates in the mechanism of protection induced by NMDA preconditioning against QA-induced seizures. Conversely, NMDA preconditioning-evoked protection against neuronal degeneration is not altered by PI3K signaling pathway inhibition. These results point to differential mechanisms regarding protection

  2. The Gut Microbiota Mediates the Anti-Seizure Effects of the Ketogenic Diet.

    PubMed

    Olson, Christine A; Vuong, Helen E; Yano, Jessica M; Liang, Qingxing Y; Nusbaum, David J; Hsiao, Elaine Y

    2018-06-14

    The ketogenic diet (KD) is used to treat refractory epilepsy, but the mechanisms underlying its neuroprotective effects remain unclear. Here, we show that the gut microbiota is altered by the KD and required for protection against acute electrically induced seizures and spontaneous tonic-clonic seizures in two mouse models. Mice treated with antibiotics or reared germ free are resistant to KD-mediated seizure protection. Enrichment of, and gnotobiotic co-colonization with, KD-associated Akkermansia and Parabacteroides restores seizure protection. Moreover, transplantation of the KD gut microbiota and treatment with Akkermansia and Parabacteroides each confer seizure protection to mice fed a control diet. Alterations in colonic lumenal, serum, and hippocampal metabolomic profiles correlate with seizure protection, including reductions in systemic gamma-glutamylated amino acids and elevated hippocampal GABA/glutamate levels. Bacterial cross-feeding decreases gamma-glutamyltranspeptidase activity, and inhibiting gamma-glutamylation promotes seizure protection in vivo. Overall, this study reveals that the gut microbiota modulates host metabolism and seizure susceptibility in mice. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Pregnant serum induces neuroinflammation and seizure activity via TNFα.

    PubMed

    Cipolla, Marilyn J; Pusic, Aya D; Grinberg, Yelena Y; Chapman, Abbie C; Poynter, Matthew E; Kraig, Richard P

    2012-04-01

    Preeclampsia is a hypertensive disorder of pregnancy that affects many organs including the brain. Neurological complications occur during preeclampsia, the most serious of which is seizure known as eclampsia. Although preeclampsia can precede the eclamptic seizure, it often occurs during normal pregnancy, suggesting that processes associated with normal pregnancy can promote neuronal excitability. Here we investigated whether circulating inflammatory mediators that are elevated late in gestation when seizure also occurs are hyperexcitable to neuronal tissue. Evoked field potentials were measured in hippocampal slices in which control horse serum that slices are normally grown in, was replaced with serum from nonpregnant or late-pregnant Wistar rats for 48 h. We found that serum from pregnant, but not nonpregnant rats, caused hyperexcitability to hippocampal neurons and seizure activity that was abrogated by inhibition of tumor necrosis factor alpha (TNFα) signaling. Additionally, application of TNFα mimicked this increased excitability. Pregnant serum also caused morphological changes in microglia characteristic of activation, and increased TNFα mRNA expression that was not seen with exposure to nonpregnant serum. However, TNFα protein was not found to be elevated in pregnant serum itself, suggesting that other circulating factors during pregnancy caused activation of hippocampal slice cells to produce a TNFα-mediated increase in neuronal excitability. Lastly, although pregnant serum caused neuroinflammation and hyperexcitability of hippocampal slices, it did not increase blood-brain barrier permeability, nor were pregnant rats from which the serum was taken undergoing seizure. Thus, the BBB has an important role in protecting the brain from circulating neuroinflammatory mediators that are hyperexcitable to the brain during pregnancy. These studies provide novel insight into the underlying cause of eclampsia without elevated blood pressure and the protective

  4. Secondary generalization of focal-onset seizures: examining the relationship between seizure propagation and epilepsy surgery outcome.

    PubMed

    Tomlinson, Samuel B; Venkataraman, Arun

    2017-04-01

    Surgical intervention often fails to achieve seizure-free results in patients with intractable epilepsy. Identifying features of the epileptic brain that dispose certain patients to unfavorable outcomes is critical for improving surgical candidacy assessments. Recent research by Martinet, Ahmad, Lepage, Cash, and Kramer ( J Neurosci 35: 9477-9490, 2015) suggests that pathways of secondary seizure generalization distinguish patients with favorable (i.e., seizure free) vs. unfavorable (i.e., seizure persistent) surgical outcomes, lending insights into the network mechanisms of epilepsy surgery failure. Copyright © 2017 the American Physiological Society.

  5. Atypical multifocal Dravet syndrome lacks generalized seizures and may show later cognitive decline.

    PubMed

    Kim, Young Ok; Bellows, Susannah; McMahon, Jacinta M; Iona, Xenia; Damiano, John; Dibbens, Leanne; Kelley, Kent; Gill, Deepak; Cross, J Helen; Berkovic, Samuel F; Scheffer, Ingrid E

    2014-01-01

    To show that atypical multifocal Dravet syndrome is a recognizable, electroclinical syndrome associated with sodium channel gene (SCN1A) mutations that readily escapes diagnosis owing to later cognitive decline and tonic seizures. Eight patients underwent electroclinical characterization. SCN1A was sequenced and copy number variations sought by multiplex ligation-dependent probe amplification. All patients were female (age range at assessment 5-26y) with median seizure onset at 6.5 months (range 4-19mo). The initial seizure was brief in seven and status epilepticus only occurred in one; three were febrile. Focal seizures occurred in four patients and bilateral convulsion in the other four. All patients developed multiple focal seizure types and bilateral convulsions, with seizure clusters in six. The most common focal seizure semiology (six out of eight) comprised unilateral clonic activity. Five also had focal or asymmetric tonic seizures. Rare or transient myoclonic seizures occurred in six individuals, often triggered by specific antiepileptic drugs. Developmental slowing occurred in all: six between 3 years and 8 years, and two around 1 year 6 months. Cognitive outcome varied from severe to mild intellectual disability. Multifocal epileptiform discharges were seen on electroencephalography. Seven out of eight patients had SCN1A mutations. Atypical, multifocal Dravet syndrome with SCN1A mutations may not be recognized because of later cognitive decline and frequent tonic seizures. © 2013 Mac Keith Press.

  6. Neonatal seizures alter NMDA glutamate receptor GluN2A and 3A subunit expression and function in hippocampal CA1 neurons

    PubMed Central

    Zhou, Chengwen; Sun, Hongyu; Klein, Peter M.; Jensen, Frances E.

    2015-01-01

    Neonatal seizures are commonly caused by hypoxic and/or ischemic injury during birth and can lead to long-term epilepsy and cognitive deficits. In a rodent hypoxic seizure (HS) model, we have previously demonstrated a critical role for seizure-induced enhancement of the AMPA subtype of glutamate receptor (GluA) in epileptogenesis and cognitive consequences, in part due to GluA maturational upregulation of expression. Similarly, as the expression and function of the N-Methyl-D-aspartate (NMDA) subtype of glutamate receptor (GluN) is also developmentally controlled, we examined how early life seizures during the critical period of synaptogenesis could modify GluN development and function. In a postnatal day (P)10 rat model of neonatal seizures, we found that seizures could alter GluN2/3 subunit composition of GluNs and physiological function of synaptic GluNs. In hippocampal slices removed from rats within 48–96 h following seizures, the amplitudes of synaptic GluN-mediated evoked excitatory postsynaptic currents (eEPSCs) were elevated in CA1 pyramidal neurons. Moreover, GluN eEPSCs showed a decreased sensitivity to GluN2B selective antagonists and decreased Mg2+ sensitivity at negative holding potentials, indicating a higher proportion of GluN2A and GluN3A subunit function, respectively. These physiological findings were accompanied by a concurrent increase in GluN2A phosphorylation and GluN3A protein. These results suggest that altered GluN function and expression could potentially contribute to future epileptogenesis following neonatal seizures, and may represent potential therapeutic targets for the blockade of future epileptogenesis in the developing brain. PMID:26441533

  7. Seizures in hospitalized cocaine users.

    PubMed

    Choy-Kwong, M; Lipton, R B

    1989-03-01

    We reviewed the records of 283 cocaine abusers consecutively admitted to a municipal hospital, and identified eight patients (2.8%) who presented with seizures. Four (1.4%) had focal or generalized seizures temporally associated with cocaine use. Based on these four cases and five previous reports, we conclude that although seizures are relatively rare in hospitalized cocaine users, they are provoked by all major routes of administration, and may be partial or generalized.

  8. Entorhinal Principal Neurons Mediate Brain-stimulation Treatments for Epilepsy.

    PubMed

    Xu, Zhenghao; Wang, Yi; Chen, Bin; Xu, Cenglin; Wu, Xiaohua; Wang, Ying; Zhang, Shihong; Hu, Weiwei; Wang, Shuang; Guo, Yi; Zhang, Xiangnan; Luo, Jianhong; Duan, Shumin; Chen, Zhong

    2016-12-01

    Brain stimulation is an alternative treatment for epilepsy. However, the neuronal circuits underlying its mechanisms remain obscure. We found that optogenetic activation (1Hz) of entorhinal calcium/calmodulin-dependent protein kinase II α (CaMKIIα)-positive neurons, but not GABAergic neurons, retarded hippocampal epileptogenesis and reduced hippocampal seizure severity, similar to that of entorhinal low-frequency electrical stimulation (LFES). Optogenetic inhibition of entorhinal CaMKIIα-positive neurons blocked the antiepileptic effect of LFES. The channelrhodopsin-2-eYFP labeled entorhinal CaMKIIα-positive neurons primarily targeted the hippocampus, and the activation of these fibers reduced hippocampal seizure severity. By combining extracellular recording and pharmacological methods, we found that activating entorhinal CaMKIIα-positive neurons induced the GABA-mediated inhibition of hippocampal neurons. Optogenetic activation of focal hippocampal GABAergic neurons mimicked this neuronal modulatory effect and reduced hippocampal seizure severity, but the anti-epileptic effect is weaker than that of entorhinal LFES, which may be due to the limited spatial neuronal modulatory effect of focal photo-stimulation. Our results demonstrate a glutamatergic-GABAergic neuronal circuit for LFES treatment of epilepsy, which is mediated by entorhinal principal neurons. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  9. Epidemiology of early stages of epilepsy: Risk of seizure recurrence after a first seizure.

    PubMed

    Rizvi, Syed; Ladino, Lady Diana; Hernandez-Ronquillo, Lizbeth; Téllez-Zenteno, José F

    2017-07-01

    A single unprovoked seizure is a frequent phenomenon in the general population and the rate of seizure recurrence can vary widely. Individual risk prognostication is crucial in predicting patient outcomes and guiding treatment decisions. In this article, we review the most important risk factors associated with an increased likelihood of seizure recurrence after a single unprovoked seizure. In summary, the presence of focal seizure, nocturnal seizure, history of prior brain injury, family history of epilepsy, abnormal neurological exam, epileptiform discharges on electroencephalography and neuroimaging abnormalities, portend increased risk of seizure recurrence. Elucidation of these risk factors in patient assessment will augment clinical decision-making and may help determine the appropriateness of instituting anti-epilepsy treatment. We also discuss the Canadian model of single seizure clinics and the potential use to assess these patients. Copyright © 2017. Published by Elsevier Ltd.

  10. miRNA Expression Profile after Status Epilepticus and Hippocampal Neuroprotection by Targeting miR-132

    PubMed Central

    Jimenez-Mateos, Eva M.; Bray, Isabella; Sanz-Rodriguez, Amaya; Engel, Tobias; McKiernan, Ross C.; Mouri, Genshin; Tanaka, Katsuhiro; Sano, Takanori; Saugstad, Julie A.; Simon, Roger P.; Stallings, Raymond L.; Henshall, David C.

    2011-01-01

    When an otherwise harmful insult to the brain is preceded by a brief, noninjurious stimulus, the brain becomes tolerant, and the resulting damage is reduced. Epileptic tolerance develops when brief seizures precede an episode of prolonged seizures (status epilepticus). MicroRNAs (miRNAs) are small, noncoding RNAs that function as post-transcriptional regulators of gene expression. We investigated how prior seizure preconditioning affects the miRNA response to status epilepticus evoked by intra-amygdalar kainic acid in mice. The miRNA was extracted from the ipsilateral CA3 subfield 24 hours after focal-onset status epilepticus in animals that had previously received either seizure preconditioning (tolerance) or no preconditioning (injury), and mature miRNA levels were measured using TaqMan low-density arrays. Expression of 21 miRNAs was increased, relative to control, after status epilepticus alone, and expression of 12 miRNAs was decreased. Increased miR-132 levels were matched with increased binding to Argonaute-2, a constituent of the RNA-induced silencing complex. In tolerant animals, expression responses of >40% of the injury-group-detected miRNAs differed, being either unchanged relative to control or down-regulated, and this included miR-132. In vivo microinjection of locked nucleic acid-modified oligonucleotides (antagomirs) against miR-132 depleted hippocampal miR-132 levels and reduced seizure-induced neuronal death. Thus, our data strongly suggest that miRNAs are important regulators of seizure-induced neuronal death. PMID:21945804

  11. Seizure-Induced Regulations of Amyloid-β, STEP61, and STEP61 Substrates Involved in Hippocampal Synaptic Plasticity

    PubMed Central

    Jang, Sung-Soo; Royston, Sara E.; Lee, Gunhee; Wang, Shuwei; Chung, Hee Jung

    2016-01-01

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline. Pathologic accumulation of soluble amyloid-β (Aβ) oligomers impairs synaptic plasticity and causes epileptic seizures, both of which contribute to cognitive dysfunction in AD. However, whether seizures could regulate Aβ-induced synaptic weakening remains unclear. Here we show that a single episode of electroconvulsive seizures (ECS) increased protein expression of membrane-associated STriatal-Enriched protein tyrosine Phosphatase (STEP61) and decreased tyrosine-phosphorylation of its substrates N-methyl D-aspartate receptor (NMDAR) subunit GluN2B and extracellular signal regulated kinase 1/2 (ERK1/2) in the rat hippocampus at 2 days following a single ECS. Interestingly, a significant decrease in ERK1/2 expression and an increase in APP and Aβ levels were observed at 3-4 days following a single ECS when STEP61 level returned to the baseline. Given that pathologic levels of Aβ increase STEP61 activity and STEP61-mediated dephosphorylation of GluN2B and ERK1/2 leads to NMDAR internalization and ERK1/2 inactivation, we propose that upregulation of STEP61 and downregulation of GluN2B and ERK1/2 phosphorylation mediate compensatory weakening of synaptic strength in response to acute enhancement of hippocampal network activity, whereas delayed decrease in ERK1/2 expression and increase in APP and Aβ expression may contribute to the maintenance of this synaptic weakening. PMID:27127657

  12. Co-induction of p75(NTR) and the associated death executor NADE in degenerating hippocampal neurons after kainate-induced seizures in the rat.

    PubMed

    Yi, Jung-Sun; Lee, Soon-Keum; Sato, Taka-Aki; Koh, Jae-Young

    2003-08-21

    Zinc induces in cultured cortical neurons both p75(NTR) and p75(NTR)-associated death executor (NADE), which together contribute to caspase-dependent neuronal apoptosis. Since zinc neurotoxicity may contribute to neuronal death following seizures, we examined whether p75(NTR) and NADE are co-induced also in rat hippocampal neurons degenerating after seizures. Staining of brain sections with a zinc-specific fluorescent dye (N-(6-methoxy-8-quinolyl)-p-carboxybenzoylsulphonamide) and acid fuchsin revealed zinc accumulation in degenerating neuronal cell bodies in CA1 and CA3 of hippocampus 24 h after kainate injection. Both anti-p75(NTR) and anti-NADE immunoreactivities appeared in zinc-accumulating/degenerating neurons in both areas. Intraventricular injection of CaEDTA, without altering the severity or time course of kainate-induced seizures, markedly attenuated the induction of p75(NTR)/NADE in hippocampus, which correlated with the decrease of caspase-3 activation and zinc accumulation/cell death. The present study has demonstrated that p75(NTR) and NADE are co-induced in neurons degenerating after kainate-induced seizures in rats, likely in a zinc-dependent manner.

  13. An Excitatory Loop with Astrocytes Contributes to Drive Neurons to Seizure Threshold

    PubMed Central

    Chiavegato, Angela; Zonta, Micaela; Cammarota, Mario; Brondi, Marco; Vetri, Francesco; Uva, Laura; Pozzan, Tullio; de Curtis, Marco; Ratto, Gian Michele; Carmignoto, Giorgio

    2010-01-01

    Seizures in focal epilepsies are sustained by a highly synchronous neuronal discharge that arises at restricted brain sites and subsequently spreads to large portions of the brain. Despite intense experimental research in this field, the earlier cellular events that initiate and sustain a focal seizure are still not well defined. Their identification is central to understand the pathophysiology of focal epilepsies and to develop new pharmacological therapies for drug-resistant forms of epilepsy. The prominent involvement of astrocytes in ictogenesis was recently proposed. We test here whether a cooperation between astrocytes and neurons is a prerequisite to support ictal (seizure-like) and interictal epileptiform events. Simultaneous patch-clamp recording and Ca2+ imaging techniques were performed in a new in vitro model of focal seizures induced by local applications of N-methyl-D-aspartic acid (NMDA) in rat entorhinal cortex slices. We found that a Ca2+ elevation in astrocytes correlates with both the initial development and the maintenance of a focal, seizure-like discharge. A delayed astrocyte activation during ictal discharges was also observed in other models (including the whole in vitro isolated guinea pig brain) in which the site of generation of seizure activity cannot be precisely monitored. In contrast, interictal discharges were not associated with Ca2+ changes in astrocytes. Selective inhibition or stimulation of astrocyte Ca2+ signalling blocked or enhanced, respectively, ictal discharges, but did not affect interictal discharge generation. Our data reveal that neurons engage astrocytes in a recurrent excitatory loop (possibly involving gliotransmission) that promotes seizure ignition and sustains the ictal discharge. This neuron–astrocyte interaction may represent a novel target to develop effective therapeutic strategies to control seizures. PMID:20405049

  14. Distemper virus encephalitis exerts detrimental effects on hippocampal neurogenesis.

    PubMed

    von Rüden, E-L; Avemary, J; Zellinger, C; Algermissen, D; Bock, P; Beineke, A; Baumgärtner, W; Stein, V M; Tipold, A; Potschka, H

    2012-08-01

    Despite knowledge about the impact of brain inflammation on hippocampal neurogenesis, data on the influence of virus encephalitis on dentate granule cell neurogenesis are so far limited. Canine distemper is considered an interesting model of virus encephalitis, which can be associated with a chronic progressing disease course and can cause symptomatic seizures. To determine the impact of canine distemper virus (CDV) infection on hippocampal neurogenesis, we compared post-mortem tissue from dogs with infection with and without seizures, from epileptic dogs with non-viral aetiology and from dogs without central nervous system diseases. The majority of animals with infection and with epilepsy of non-viral aetiology exhibited neuronal progenitor numbers below the age average in controls. Virus infection with and without seizures significantly decreased the mean number of neuronal progenitor cells by 43% and 76% as compared to age-matched controls. Ki-67 labelling demonstrated that hippocampal cell proliferation was neither affected by infection nor by epilepsy of non-viral aetiology. Analysis of CDV infection in cells expressing caspase-3, doublecortin or Ki-67 indicated that infection of neuronal progenitor cells is extremely rare and suggests that infection might damage non-differentiated progenitor cells, hamper neuronal differentiation and promote glial differentiation. A high inter-individual variance in the number of lectin-reactive microglial cells was evident in dogs with distemper infection. Statistical analyses did not reveal a correlation between the number of lectin-reactive microglia cells and neuronal progenitor cells. Our data demonstrate that virus encephalitis with and without seizures can exert detrimental effects on hippocampal neurogenesis, which might contribute to long-term consequences of the disease. The lack of a significant impact of distemper virus on Ki-67-labelled cells indicates that the infection affected neuronal differentiation and

  15. Stimulus-induced, sleep-bound, focal seizures: a case report.

    PubMed

    Siclari, Francesca; Nobili, Lino; Lo Russo, Giorgio; Moscato, Alessio; Buck, Alfred; Bassetti, Claudio L; Khatami, Ramin

    2011-12-01

    In nocturnal frontal lobe epilepsy (NFLE), seizures occur almost exclusively during NREM sleep. Why precisely these seizures are sleep-bound remains unknown. Studies of patients with nonlesional familial forms of NFLE have suggested the arousal system may play a major role in their pathogenesis. We report the case of a patient with pharmaco-resistant, probably cryptogenic form of non-familial NFLE and strictly sleep-bound seizures that could be elicited by alerting stimuli and were associated with ictal bilateral thalamic and right orbital-insular hyperperfusion on SPECT imaging. Case report. University Hospital Zurich. One patient with pharmaco-resistant epilepsy. This case shows that the arousal system plays a fundamental role also in cryptogenic non-familial forms of NFLE.

  16. Recognition Memory Is Impaired in Children after Prolonged Febrile Seizures

    ERIC Educational Resources Information Center

    Martinos, Marina M.; Yoong, Michael; Patil, Shekhar; Chin, Richard F. M.; Neville, Brian G.; Scott, Rod C.; de Haan, Michelle

    2012-01-01

    Children with a history of a prolonged febrile seizure show signs of acute hippocampal injury on magnetic resonance imaging. In addition, animal studies have shown that adult rats who suffered febrile seizures during development reveal memory impairments. Together, these lines of evidence suggest that memory impairments related to hippocampal…

  17. Remembering preservation in hippocampal amnesia

    PubMed Central

    Clark, Ian A.; Maguire, Eleanor A.

    2017-01-01

    The lesion-deficit model dominates neuropsychology. This is unsurprising given powerful demonstrations that focal brain lesions can affect specific aspects of cognition. Nowhere is this more evident than in patients with bilateral hippocampal damage. In the last sixty years the amnesia and other impairments exhibited by these patients have helped to delineate the functions of the hippocampus and shape the field of memory. We do not question the value of this approach. However, less prominent are the cognitive processes that remain intact following hippocampal lesions. Here, we collate the piecemeal reports of preservation of function following focal bilateral hippocampal damage, highlighting a wealth of information often veiled by the field’s focus on deficits. We consider how a systematic understanding of what is preserved as well as what is lost could add an important layer of precision to models of memory and the hippocampus. PMID:26361051

  18. The biochemical changes in hippocampal formation occurring in normal and seizure experiencing rats as a result of a ketogenic diet.

    PubMed

    Chwiej, Joanna; Skoczen, Agnieszka; Janeczko, Krzysztof; Kutorasinska, Justyna; Matusiak, Katarzyna; Figiel, Henryk; Dumas, Paul; Sandt, Christophe; Setkowicz, Zuzanna

    2015-04-07

    In this study, ketogenic diet-induced biochemical changes occurring in normal and epileptic hippocampal formations were compared. Four groups of rats were analyzed, namely seizure experiencing animals and normal rats previously fed with ketogenic (KSE and K groups respectively) or standard laboratory diet (NSE and N groups respectively). Synchrotron radiation based Fourier-transform infrared microspectroscopy was used for the analysis of distributions of the main organic components (proteins, lipids, compounds containing phosphate group(s)) and their structural modifications as well as anomalies in creatine accumulation with micrometer spatial resolution. Infrared spectra recorded in the molecular layers of the dentate gyrus (DG) areas of normal rats on a ketogenic diet (K) presented increased intensity of the 1740 cm(-1) absorption band. This originates from the stretching vibrations of carbonyl groups and probably reflects increased accumulation of ketone bodies occurring in animals on a high fat diet compared to those fed with a standard laboratory diet (N). The comparison of K and N groups showed, moreover, elevated ratios of absorbance at 1634 and 1658 cm(-1) for DG internal layers and increased accumulation of creatine deposits in sector 3 of the Ammon's horn (CA3) hippocampal area of ketogenic diet fed rats. In multiform and internal layers of CA3, seizure experiencing animals on ketogenic diet (KSE) presented a lower ratio of absorbance at 1634 and 1658 cm(-1) compared to rats on standard laboratory diet (NSE). Moreover, in some of the examined cellular layers, the increased intensity of the 2924 cm(-1) lipid band as well as the massifs of 2800-3000 cm(-1) and 1360-1480 cm(-1), was found in KSE compared to NSE animals. The intensity of the 1740 cm(-1) band was diminished in DG molecular layers of KSE rats. The ketogenic diet did not modify the seizure induced anomalies in the unsaturation level of lipids or the number of creatine deposits.

  19. Global and regional functional connectivity maps of neural oscillations in focal epilepsy

    PubMed Central

    Englot, Dario J.; Hinkley, Leighton B.; Kort, Naomi S.; Imber, Brandon S.; Mizuiri, Danielle; Honma, Susanne M.; Findlay, Anne M.; Garrett, Coleman; Cheung, Paige L.; Mantle, Mary; Tarapore, Phiroz E.; Knowlton, Robert C.; Chang, Edward F.; Nagarajan, Srikantan S.

    2015-01-01

    Intractable focal epilepsy is a devastating disorder with profound effects on cognition and quality of life. Epilepsy surgery can lead to seizure freedom in patients with focal epilepsy; however, sometimes it fails due to an incomplete delineation of the epileptogenic zone. Brain networks in epilepsy can be studied with resting-state functional connectivity analysis, yet previous investigations using functional magnetic resonance imaging or electrocorticography have produced inconsistent results. Magnetoencephalography allows non-invasive whole-brain recordings, and can be used to study both long-range network disturbances in focal epilepsy and regional connectivity at the epileptogenic zone. In magnetoencephalography recordings from presurgical epilepsy patients, we examined: (i) global functional connectivity maps in patients versus controls; and (ii) regional functional connectivity maps at the region of resection, compared to the homotopic non-epileptogenic region in the contralateral hemisphere. Sixty-one patients were studied, including 30 with mesial temporal lobe epilepsy and 31 with focal neocortical epilepsy. Compared with a group of 31 controls, patients with epilepsy had decreased resting-state functional connectivity in widespread regions, including perisylvian, posterior temporo-parietal, and orbitofrontal cortices (P < 0.01, t-test). Decreased mean global connectivity was related to longer duration of epilepsy and higher frequency of consciousness-impairing seizures (P < 0.01, linear regression). Furthermore, patients with increased regional connectivity within the resection site (n = 24) were more likely to achieve seizure postoperative seizure freedom (87.5% with Engel I outcome) than those with neutral (n = 15, 64.3% seizure free) or decreased (n = 23, 47.8% seizure free) regional connectivity (P < 0.02, chi-square). Widespread global decreases in functional connectivity are observed in patients with focal epilepsy, and may reflect deleterious

  20. Rasmussen's encephalitis presenting as focal cortical dysplasia

    PubMed Central

    O'Rourke, D.J.; Bergin, A.; Rotenberg, A.; Peters, J.; Gorman, M.; Poduri, A.; Cryan, J.; Lidov, H.; Madsen, J.; Harini, C.

    2014-01-01

    Rasmussen's encephalitis is a rare syndrome characterized by intractable seizures, often associated with epilepsia partialis continua and symptoms of progressive hemispheric dysfunction. Seizures are usually the hallmark of presentation, but antiepileptic drug treatment fails in most patients and is ineffective against epilepsia partialis continua, which often requires surgical intervention. Co-occurrence of focal cortical dysplasia has only rarely been described and may have implications regarding pathophysiology and management. We describe a rare case of dual pathology of Rasmussen's encephalitis presenting as a focal cortical dysplasia (FCD) and discuss the literature on this topic. PMID:25667877

  1. Comparison of electric field strength and spatial distribution of electroconvulsive therapy and magnetic seizure therapy in a realistic human head model

    PubMed Central

    Lee, Won Hee; Lisanby, Sarah H.; Laine, Andrew F.; Peterchev, Angel V.

    2017-01-01

    Background This study examines the strength and spatial distribution of the electric field induced in the brain by electroconvulsive therapy (ECT) and magnetic seizure therapy (MST). Methods The electric field induced by standard (bilateral, right unilateral, and bifrontal) and experimental (focal electrically administered seizure therapy and frontomedial) ECT electrode configurations as well as a circular MST coil configuration was simulated in an anatomically realistic finite element model of the human head. Maps of the electric field strength relative to an estimated neural activation threshold were used to evaluate the stimulation strength and focality in specific brain regions of interest for these ECT and MST paradigms and various stimulus current amplitudes. Results The standard ECT configurations and current amplitude of 800–900 mA produced the strongest overall stimulation with median of 1.8–2.9 times neural activation threshold and more than 94% of the brain volume stimulated at suprathreshold level. All standard ECT electrode placements exposed the hippocampi to suprathreshold electric field, although there were differences across modalities with bilateral and right unilateral producing respectively the strongest and weakest hippocampal stimulation. MST stimulation is up to 9 times weaker compared to conventional ECT, resulting in direct activation of only 21% of the brain. Reducing the stimulus current amplitude can make ECT as focal as MST. Conclusions The relative differences in electric field strength may be a contributing factor for the cognitive sparing observed with right unilateral compared to bilateral ECT, and MST compared to right unilateral ECT. These simulations could help understand the mechanisms of seizure therapies and develop interventions with superior risk/benefit ratio. PMID:27318858

  2. Sex differences in seizure types and symptoms.

    PubMed

    Carlson, Chad; Dugan, Patricia; Kirsch, Heidi E; Friedman, Daniel

    2014-12-01

    Despite the increasing interest in sex differences in disease manifestations and responses to treatment, very few data are available on sex differences in seizure types and semiology. The Epilepsy Phenome/Genome Project (EPGP) is a large-scale, multi-institutional, collaborative study that aims to create a comprehensive repository of detailed clinical information and DNA samples from a large cohort of people with epilepsy. We used this well-characterized cohort to explore differences in seizure types as well as focal seizure symptoms between males and females. We reviewed the EPGP database and identified individuals with generalized epilepsy of unknown etiology (GE) (n = 760; female: 446, male: 314), nonacquired focal epilepsy (NAFE) (n = 476; female: 245, male: 231), or both (n = 64; female: 33, male: 31). Demographic data along with characterization of seizure type and focal seizure semiologies were examined. In GE, males reported atonic seizures more frequently than females (6.5% vs. 1.7%; p < 0.001). No differences were observed in other generalized seizure types. In NAFE, no sex differences were seen for seizure types with or without alteration of consciousness or progression to secondary generalization. Autonomic (16.4% vs. 26.6%; p = 0.005), psychic (26.7% vs. 40.3%; p = 0.001), and visual (10.3% vs. 19.9%; p = 0.002) symptoms were more frequently reported in females than males. Specifically, of psychic symptoms, more females than males endorsed déjà vu (p = 0.001) but not forced thoughts, derealization/depersonalization, jamais vu, or fear. With corrections for multiple comparisons, there were no significant differences in aphasic, motor, somatosensory, gustatory, olfactory, auditory, vertiginous, or ictal headache symptoms between sexes. Significant differences between the sexes were observed in the reporting of atonic seizures, which were more common in males with GE, and for autonomic, visual, and psychic symptoms associated with NAFE, which were more

  3. Sex Differences in Seizure Types and Symptoms

    PubMed Central

    Carlson, Chad; Dugan, Patricia; Kirsch, Heidi E; Friedman, Daniel

    2014-01-01

    Background Despite the increasing interest in sex differences in disease manifestations and responses to treatment, very few data are available on sex differences in seizure types and semiology. The Epilepsy Phenome/Genome Project (EPGP) is a large-scale, multi-institutional, collaborative study that aims to create a comprehensive repository of detailed clinical information and DNA samples from a large cohort of people with epilepsy. We used this well-characterized cohort to explore differences in seizure types as well as focal seizure symptoms between males and females. Methods We reviewed the EPGP database and identified individuals with generalized epilepsy of unknown etiology (GE) (n=760; female 446, male 314), non-acquired focal epilepsy (NAFE) (n=476; female 245, male 231), or both (n=64; female 33, male 31). Demographic data along with characterization of seizure type and focal seizure semiologies were examined. Results In GE, males reported atonic seizures more frequently than females (6.5% vs. 1.7%; p<0.001). No differences were observed in other generalized seizure types. In NAFE, no sex differences were seen for seizure types with or without alteration of consciousness or progression to secondary generalization. Autonomic (16.4% vs. 26.6%; p=0.005), psychic (26.7% vs. 40.3%; p=0.001), and visual symptoms (10.3% vs. 19.9%; p=0.002) were more frequently reported in females than males. Specifically, of psychic symptoms, more females than males endorsed déjà vu (p=0.001), but not forced thoughts, derealization/depersonalization, jamais vu, or fear. With corrections for multiple comparisons, there were no significant differences in aphasic, motor, somatosensory, gustatory, olfactory, auditory, vertiginous, or ictal headache symptoms between sexes. Conclusions Significant differences between the sexes were observed in the reporting of atonic seizures, which was more common in males with GE, and for autonomic, visual, and psychic symptoms associated with NAFE

  4. Hippocampal interictal epileptiform activity disrupts cognition in humans

    PubMed Central

    Kleen, Jonathan K.; Scott, Rod C.; Holmes, Gregory L.; Roberts, David W.; Rundle, Melissa M.; Testorf, Markus; Lenck-Santini, Pierre-Pascal

    2013-01-01

    Objective: We investigated whether interictal epileptiform discharges (IED) in the human hippocampus are related to impairment of specific memory processes, and which characteristics of hippocampal IED are most associated with memory dysfunction. Methods: Ten patients had depth electrodes implanted into their hippocampi for preoperative seizure localization. EEG was recorded during 2,070 total trials of a short-term memory task, with memory processing categorized into encoding, maintenance, and retrieval. The influence of hippocampal IED on these processes was analyzed and adjusted to account for individual differences between patients. Results: Hippocampal IED occurring in the memory retrieval period decreased the likelihood of a correct response when they were contralateral to the seizure focus (p < 0.05) or bilateral (p < 0.001). Bilateral IED during the memory maintenance period had a similar effect (p < 0.01), particularly with spike-wave complexes of longer duration (p < 0.01). IED during encoding had no effect, and reaction time was also unaffected by IED. Conclusions: Hippocampal IED in humans may disrupt memory maintenance and retrieval, but not encoding. The particular effects of bilateral IED and those contralateral to the seizure focus may relate to neural compensation in the more functional hemisphere. This study provides biological validity to animal models in the study of IED-related transient cognitive impairment. Moreover, it strengthens the argument that IED may contribute to cognitive impairment in epilepsy depending upon when and where they occur. PMID:23685931

  5. A Functional-Genetic Scheme for Seizure Forecasting in Canine Epilepsy.

    PubMed

    Bou Assi, Elie; Nguyen, Dang K; Rihana, Sandy; Sawan, Mohamad

    2018-06-01

    The objective of this work is the development of an accurate seizure forecasting algorithm that considers brain's functional connectivity for electrode selection. We start by proposing Kmeans-directed transfer function, an adaptive functional connectivity method intended for seizure onset zone localization in bilateral intracranial EEG recordings. Electrodes identified as seizure activity sources and sinks are then used to implement a seizure-forecasting algorithm on long-term continuous recordings in dogs with naturally-occurring epilepsy. A precision-recall genetic algorithm is proposed for feature selection in line with a probabilistic support vector machine classifier. Epileptic activity generators were focal in all dogs confirming the diagnosis of focal epilepsy in these animals while sinks spanned both hemispheres in 2 of 3 dogs. Seizure forecasting results show performance improvement compared to previous studies, achieving average sensitivity of 84.82% and time in warning of 0.1. Achieved performances highlight the feasibility of seizure forecasting in canine epilepsy. The ability to improve seizure forecasting provides promise for the development of EEG-triggered closed-loop seizure intervention systems for ambulatory implantation in patients with refractory epilepsy.

  6. Pathology-Based Approach to Seizure Outcome After Surgery for Pharmacoresistant Medial Temporal Lobe Epilepsy.

    PubMed

    Martinoni, Matteo; Berti, Pier Paolo; Marucci, Gianluca; Rubboli, Guido; Volpi, Lilia; Riguzzi, Patrizia; Marliani, Federica; Toni, Francesco; Bisulli, Francesca; Tinuper, Paolo; Michelucci, Roberto; Baruzzi, Agostino; Giulioni, Marco

    2016-06-01

    Hippocampal sclerosis (HS) is the most common cause of drug-resistant medial temporal lobe epilepsy (MTLE). Structural abnormalities such as HS, granule cell pathology (GCP), and focal cortical dysplasia (FCD) have been classified histopathologically, possibly allowing a more accurate assessment of prognostic seizure and neuropsychologic outcomes. We correlated seizure outcome with comprehensive temporal lobe pathologic findings, identified according to the most recent classification systems of HS, GCP, and FCD. All the 83 patients who underwent anterior temporal lobectomy (ATL) for drug-resistant MTLE and with a proven diagnosis of HS between April 2001 and May 2014 were collected. Patients were divided in 2 main groups: 1) isolated HS with/without GCP (HS +/- GCP); and 2) HS associated with FCD with/without GCP (HS+FCD +/- GCP). Patients were followed up at least 1 year, and seizure outcome was reported in accordance with Engel classification. Group I: HS +/- GCP: Statistical analysis confirmed a better outcome in HS + GCP patients than in HS-no GCP (P < 0.05). Moreover, a better outcome for the patients affected by GCP type I was observed (P < 0.05). Group II: HS+FCD +/- GCP: Patients with HS variant type I presented a better seizure outcome than the patients with HS type II (Engel class IA HS type I vs. type II: 69% vs. 40%). A pathology-based approach to epilepsy surgery might improve the interpretation of the results, could predict which cases will enjoy a better seizure outcome, and could help to the comprehension of the causes of failures. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Occipitoparietal epilepsy, hippocampal atrophy, and congenital developmental abnormalities.

    PubMed

    Lawn, N; Londono, A; Sawrie, S; Morawetz, R; Martin, R; Gilliam, F; Faught, E; Kuzniecky, R

    2000-12-01

    Diagnostic uncertainty may arise in patients with occipitoparietal epilepsy when there is neuroimaging evidence of a posterior quadrant lesion and coexistent hippocampal abnormalities ("dual pathology"). It is not known whether hippocampal atrophy (HA) in these patients results from seizure propagation to temporolimbic structures or whether it is part of the pathological process underlying the occipitoparietal epilepsy. Clarification of this issue may have a significant bearing on the management of these patients. We studied 20 patients with occipitoparietal epilepsy and neuroimaging or pathologic evidence of a congenital developmental abnormality. Normalized hippocampal volumes were obtained in all patients. The medical records and video-EEG recordings were analyzed to correlate the MRI findings with clinical data, seizure semiology, and EEG findings. HA was found in seven patients (35%). Neuroimaging abnormalities concordant with the side of HA were seen in all cases. There was clinical or EEG evidence of temporal spread in 12 patients. There was no correlation between the presence of HA and temporal lobe spread. The only clinical factor associated with HA in this series was a younger age of seizure onset. HA in patients with occipitoparietal epilepsy due to congenital developmental abnormalities is most likely to be a marker of a more widespread process related to a common pathogenesis during prenatal or perinatal development. HA in these patients is unlikely to be the result of secondary spread from an extrahippocampal focus. Surgical treatment should be tailored toward the primary epileptogenic zone rather the site of seizure spread.

  8. Proton MR spectroscopy in patients with acute temporal lobe seizures.

    PubMed

    Castillo, M; Smith, J K; Kwock, L

    2001-01-01

    Decreases in N-acetyl aspartate (NAA) as seen by proton MR spectroscopy are found in hippocampal sclerosis, and elevated levels of lipids/lactate have been observed after electroconvulsive therapy. Our purpose was to determine whether increased levels of lipids/lactate are found in patients with acute seizures of hippocampal origin. Seventeen patients with known temporal lobe epilepsy underwent proton MR spectroscopy of the mesial temporal lobes within 24 hours of their last seizure. Four of them were restudied when they were seizure-free. Five healthy individuals were used as control subjects. All MR spectroscopy studies were obtained using a single-voxel technique with TEs of 135 and 270. The relationship between the presence of lipids/lactate and seizures was tested using Fisher's exact test. Mean and standard deviations for NAA/creatine (Cr) were obtained in the hippocampi in patients with seizures on initial and follow-up studies and these values were compared with those in the control subjects. Seizure lateralization was obtained in 15 patients. Of the 17 seizure locations that involved hippocampi, 16 showed lipids/lactate by proton MR spectroscopy. Of the 13 hippocampi not directly affected by seizures, 10 showed no lipids/lactate and three showed lipids/lactate. The relationship between lipids/lactate and seizure location was confirmed. A comparison of NAA/Cr ratios for the involved hippocampi with those in control subjects showed significant differences on initial MR spectroscopy; however, no significant difference was found between acute and follow-up NAA/Cr ratios in hippocampi affected by seizures. Lipids/lactate were present in the hippocampi of patients with acute seizures and decreased when the patients were seizure-free. Thus, lipids/lactate may be a sensitive marker for acute temporal lobe seizures.

  9. miRNA Expression profile after status epilepticus and hippocampal neuroprotection by targeting miR-132.

    PubMed

    Jimenez-Mateos, Eva M; Bray, Isabella; Sanz-Rodriguez, Amaya; Engel, Tobias; McKiernan, Ross C; Mouri, Genshin; Tanaka, Katsuhiro; Sano, Takanori; Saugstad, Julie A; Simon, Roger P; Stallings, Raymond L; Henshall, David C

    2011-11-01

    When an otherwise harmful insult to the brain is preceded by a brief, noninjurious stimulus, the brain becomes tolerant, and the resulting damage is reduced. Epileptic tolerance develops when brief seizures precede an episode of prolonged seizures (status epilepticus). MicroRNAs (miRNAs) are small, noncoding RNAs that function as post-transcriptional regulators of gene expression. We investigated how prior seizure preconditioning affects the miRNA response to status epilepticus evoked by intra-amygdalar kainic acid in mice. The miRNA was extracted from the ipsilateral CA3 subfield 24 hours after focal-onset status epilepticus in animals that had previously received either seizure preconditioning (tolerance) or no preconditioning (injury), and mature miRNA levels were measured using TaqMan low-density arrays. Expression of 21 miRNAs was increased, relative to control, after status epilepticus alone, and expression of 12 miRNAs was decreased. Increased miR-132 levels were matched with increased binding to Argonaute-2, a constituent of the RNA-induced silencing complex. In tolerant animals, expression responses of >40% of the injury-group-detected miRNAs differed, being either unchanged relative to control or down-regulated, and this included miR-132. In vivo microinjection of locked nucleic acid-modified oligonucleotides (antagomirs) against miR-132 depleted hippocampal miR-132 levels and reduced seizure-induced neuronal death. Thus, our data strongly suggest that miRNAs are important regulators of seizure-induced neuronal death. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  10. Lateralizing value of unilateral relative ictal immobility in patients with refractory focal seizures--Looking beyond unilateral automatisms.

    PubMed

    Agarwal, Priya; Kaul, Bhavna; Shukla, Garima; Srivastava, Achal; Singh, Mamta Bhushan; Goyal, Vinay; Behari, Madhuri; Suri, Ashish; Gupta, Aditya; Garg, Ajay; Gaikwad, Shailesh; Bal, C S

    2015-12-01

    Ictal motor phenomena play a crucial role in the localization of seizure focus in the management of refractory focal epilepsy. While the importance of unilateral automatisms is well established, little attention is paid to the contralateral relatively immobile limb. In cases where automatisms mimic clonic or dystonic movements and in the absence of previously well-established signs, unilateral relative ictal immobility (RII) is potentially useful as a lateralizing sign. This study was carried out to examine the lateralizing value of this sign and to define its characteristics among patients of refractory focal epilepsy. VEEGs of 69 consecutive patients of refractory focal epilepsy who had undergone epilepsy surgery at our center over last four years were reviewed and analyzed for the presence of RII. Unilateral RII was defined as a paucity of movement in one limb lasting for at least 10s while the contralateral limb showed purposive or semi-purposive movements (in the absence of tonic or dystonic posturing or clonic movements in the involved limb). The findings were seen in the light of VEEG, radiological and nuclear imaging data, and with post-surgical outcome. Unilateral RII as a lateralizing sign was found in 24 of 69 patients (34.78%), consisting of both temporal and extra temporal epilepsy, with 100% concordance with VEEG and MRI data. All patients demonstrating this sign had a good post-surgical outcome. RII, when well characterized is a frequent and reliable lateralizing sign in patients of refractory focal epilepsy. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  11. The use of routine EEG in acute ischemic stroke patients without seizures: generalized but not focal EEG pathology is associated with clinical deterioration.

    PubMed

    Wolf, Marc E; Ebert, Anne D; Chatzikonstantinou, Anastasios

    2017-05-01

    Specialized electroencephalography (EEG) methods have been used to provide clues about stroke features and prognosis. However, the value of routine EEG in stroke patients without (suspected) seizures has been somewhat neglected. We aimed to assess this in a group of acute ischemic stroke patients in regard to short-term prognosis and basic stroke features. We assessed routine (10-20) EEG findings in 69 consecutive acute ischemic stroke patients without seizures. Associations between EEG abnormalities and NIHSS scores, clinical improvement or deterioration as well as MRI stroke characteristics were evaluated. Mean age was 69 ± 18 years, 43 of the patients (62.3%) were men. Abnormal EEG was found in 40 patients (58%) and was associated with higher age (p = 0.021). The most common EEG pathology was focal slowing (30; 43.5%). No epileptiform potentials were found. Abnormal EEG in general and generalized or focal slowing in particular was significantly associated with higher NIHSS score on admission and discharge as well as with hemorrhagic transformation of the ischemic lesion. Abnormal EEG and generalized (but not focal) slowing were associated with clinical deterioration ( p = 0.036, p = 0.003). Patients with lacunar strokes had no EEG abnormalities. Abnormal EEG in general and generalized slowing in particular are associated with clinical deterioration after acute ischemic stroke. The study demonstrates the value of routine EEG as a simple diagnostic tool in the evaluation of stroke patients especially with regard to short-term prognosis.

  12. SOX11 identified by target gene evaluation of miRNAs differentially expressed in focal and non-focal brain tissue of therapy-resistant epilepsy patients.

    PubMed

    Haenisch, Sierk; Zhao, Yi; Chhibber, Aparna; Kaiboriboon, Kitti; Do, Lynn V; Vogelgesang, Silke; Barbaro, Nicholas M; Alldredge, Brian K; Lowenstein, Daniel H; Cascorbi, Ingolf; Kroetz, Deanna L

    2015-05-01

    MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally control the expression of their target genes via RNA interference. There is increasing evidence that expression of miRNAs is dysregulated in neuronal disorders, including epilepsy, a chronic neurological disorder characterized by spontaneous recurrent seizures. Mesial temporal lobe epilepsy (MTLE) is a common type of focal epilepsy in which disease-induced abnormalities of hippocampal neurogenesis in the subgranular zone as well as gliosis and neuronal cell loss in the cornu ammonis area are reported. We hypothesized that in MTLE altered miRNA-mediated regulation of target genes could be involved in hippocampal cell remodeling. A miRNA screen was performed in hippocampal focal and non-focal brain tissue samples obtained from the temporal neocortex (both n=8) of MTLE patients. Out of 215 detected miRNAs, two were differentially expressed (hsa-miR-34c-5p: mean increase of 5.7 fold (p=0.014), hsa-miR-212-3p: mean decrease of 76.9% (p=0.0014)). After in-silico target gene analysis and filtering, reporter gene assays confirmed RNA interference for hsa-miR-34c-5p with 3'-UTR sequences of GABRA3, GRM7 and GABBR2 and for hsa-miR-212-3p with 3'-UTR sequences of SOX11, MECP2, ADCY1 and ABCG2. Reporter gene assays with mutated 3'-UTR sequences of the transcription factor SOX11 identified two different binding sites for hsa-miR-212-3p and its primary transcript partner hsa-miR-132-3p. Additionally, there was an inverse time-dependent expression of Sox11 and miR-212-3p as well as miR-132-3p in rat neonatal cortical neurons. Transfection of neurons with anti-miRs for miR-212-3p and miR-132-3p suggest that both miRNAs work synergistically to control Sox11 expression. Taken together, these results suggest that differential miRNA expression in neurons could contribute to an altered function of the transcription factor SOX11 and other genes in the setting of epilepsy, resulting not only in impaired neural

  13. Effects of hippocampal high-frequency electrical stimulation in memory formation and their association with amino acid tissue content and release in normal rats.

    PubMed

    Luna-Munguía, Hiram; Meneses, Alfredo; Peña-Ortega, Fernando; Gaona, Andres; Rocha, Luisa

    2012-01-01

    Hippocampal high frequency electrical stimulation (HFS) at 130 Hz has been proposed as a therapeutical strategy to control neurological disorders such as intractable temporal lobe epilepsy (TLE). This study was carried out to determine the effects of hippocampal HFS on the memory process and the probable involvement of amino acids. Using the autoshaping task, we found that animals receiving hippocampal HFS showed augmented short-term, but not long-term memory formation, an effect blocked by bicuculline pretreatment and associated with enhanced tissue levels of amino acids in hippocampus. In addition, microdialysis experiments revealed high extracellular levels of glutamate, aspartate, glycine, taurine, and alanine during the application of hippocampal HFS. In contrast, GABA release augmented during HFS and remained elevated for more than 1 h after the stimulation was ended. HFS had minimal effects on glutamine release. The present results suggest that HFS has an activating effect on specific amino acids in normal hippocampus that may be involved in the enhanced short-term memory formation. These data further provide experimental support for the concept that hippocampus may be a promising target for focal stimulation to treat intractable seizures in humans. Copyright © 2010 Wiley Periodicals, Inc., Inc.

  14. Insulin growth factor-1 (IGF-1) enhances hippocampal excitatory and seizure activity through IGF-1 receptor-mediated mechanisms in the epileptic brain.

    PubMed

    Jiang, Guohui; Wang, Wei; Cao, Qingqing; Gu, Juan; Mi, Xiujuan; Wang, Kewei; Chen, Guojun; Wang, Xuefeng

    2015-12-01

    Insulin-like growth factor-1 (IGF-1) is known to promote neurogenesis and survival. However, recent studies have suggested that IGF-1 regulates neuronal firing and excitatory neurotransmission. In the present study, focusing on temporal lobe epilepsy, we found that IGF-1 levels and IGF-1 receptor activation are increased in human epileptogenic tissues, and pilocarpine- and pentylenetetrazole-treated rat models. Using an acute model of seizures, we showed that lateral cerebroventricular infusion of IGF-1 elevates IGF-1 receptor (IGF-1R) signalling before pilocarpine application had proconvulsant effects. In vivo electroencephalogram recordings and power spectrogram analysis of local field potential revealed that IGF-1 promotes epileptiform activities. This effect is diminished by co-application of an IGF-1R inhibitor. In an in vitro electrophysiological study, we demonstrated that IGF-1 enhancement of excitatory neurotransmission and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor- and N-methyl-D-aspartate receptor-mediated currents is inhibited by IGF-1R inhibitor. Finally, activation of extracellular signal-related kinase (ERK)-1/2 and protein kinase B (Akt) in seizures in rats is increased by exogenous IGF-1 and diminished by picropodophyllin. A behavioural study reveals that the ERK1/2 or Akt inhibitor attenuates seizure activity. These results indicate that increased IGF-1 levels after recurrent hippocampal neuronal firings might, in turn, promote seizure activity via IGF-1R-dependent mechanisms. The present study presents a previously unappreciated role of IGF-1R in the development of seizure activity. © 2015 Authors; published by Portland Press Limited.

  15. Continuous Monitoring via Tethered Electroencephalography of Spontaneous Recurrent Seizures in Mice

    PubMed Central

    Bin, Na-Ryum; Song, Hongmei; Wu, Chiping; Lau, Marcus; Sugita, Shuzo; Eubanks, James H.; Zhang, Liang

    2017-01-01

    We describe here a simple, cost-effective apparatus for continuous tethered electroencephalographic (EEG) monitoring of spontaneous recurrent seizures in mice. We used a small, low torque slip ring as an EEG commutator, mounted the slip ring onto a standard mouse cage and connected rotary wires of the slip ring directly to animal's implanted headset. Modifications were made in the cage to allow for a convenient installation of the slip ring and accommodation of animal ambient activity. We tested the apparatus for hippocampal EEG recordings in adult C57 black mice. Spontaneous recurrent seizures were induced using extended hippocampal kindling (≥95 daily stimulation). Control animals underwent similar hippocampal electrode implantations but no stimulations were given. Combined EEG and webcam monitoring were performed for 24 h daily for 5–9 consecutive days. During the monitoring periods, the animals moved and accessed water and food freely and showed no apparent restriction in ambient cage activities. Ictal-like hippocampal EEG discharges and concurrent convulsive behaviors that are characteristics of spontaneous recurrent seizures were reliably recorded in a majority of the monitoring experiments in extendedly kindled but not in control animals. However, 1–2 rotary wires were disconnected from the implanted headset in some animals after continuous recordings for ≥5 days. The key features and main limitations of our recording apparatus are discussed. PMID:28959196

  16. A feasibility study of a new method for electrically producing seizures in man: focal electrically administered seizure therapy [FEAST].

    PubMed

    Nahas, Ziad; Short, Baron; Burns, Carol; Archer, Melanie; Schmidt, Matthew; Prudic, Joan; Nobler, Mitchell S; Devanand, D P; Fitzsimons, Linda; Lisanby, Sarah H; Payne, Nancy; Perera, Tarique; George, Mark S; Sackeim, Harold A

    2013-05-01

    Electroconvulsive therapy (ECT) remains the most effective acute treatment for severe major depression, but with significant risk of adverse cognitive effects. Unidirectional electrical stimulation with a novel electrode placement and geometry (Focal Electrically Administered Seizure Therapy (FEAST)) has been proposed as a means to initiate seizures in prefrontal cortex prior to secondary generalization. As such, it may have fewer cognitive side effects than traditional ECT. We report on its first human clinical application. Seventeen unmedicated depressed adults (5 men; 3 bipolar disorder; age 53 ± 16 years) were recruited after being referred for ECT. Open-label FEAST was administered with a modified spECTrum 5000Q device and a traditional ECT dosing regimen until patients clinically responded. Clinical and cognitive assessments were obtained at baseline, and end of course. Time to orientation recovery, a predictor of long-term amnestic effects, was assessed at each treatment. Nonresponders to FEAST were transitioned to conventional ECT. One patient withdrew from the study after a single titration session. After the course of FEAST (median 10 sessions), there was a 46.1 ± 35.5% improvement in Hamilton Rating Scale for Depression (HRSD24) scores compared to baseline (33.1 ± 6.8, 16.8 ± 10.9; P < 0.0001). Eight of 16 patients met response criteria (50% decrease in HRSD24) and 5/16 met remission criteria (HRSD24 ≤ 10). Patients achieved full re-orientation (4 of 5 items) in 5.5 ± 6.4 min (median = 3.6), timed from when their eyes first opened after treatment. In this feasibility study, FEAST produced clinically meaningful antidepressant improvement, with relatively short time to reorientation. Our preliminary work first in primates and now depressed adults demonstrates that FEAST is feasible, safe, well-tolerated and, if efficacy can be optimized, has potential to replace traditional ECT. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. The localizing value of ictal EEG in focal epilepsy.

    PubMed

    Foldvary, N; Klem, G; Hammel, J; Bingaman, W; Najm, I; Lüders, H

    2001-12-11

    To investigate the lateralization and localization of ictal EEG in focal epilepsy. A total of 486 ictal EEG of 72 patients with focal epilepsy arising from the mesial temporal, neocortical temporal, mesial frontal, dorsolateral frontal, parietal, and occipital regions were analyzed. Surface ictal EEG was adequately localized in 72% of cases, more often in temporal than extratemporal epilepsy. Localized ictal onsets were seen in 57% of seizures and were most common in mesial temporal lobe epilepsy (MTLE), lateral frontal lobe epilepsy (LFLE), and parietal lobe epilepsy, whereas lateralized onsets predominated in neocortical temporal lobe epilepsy and generalized onsets in mesial frontal lobe epilepsy (MFLE) and occipital lobe epilepsy. Approximately two-thirds of seizures were localized, 22% generalized, 4% lateralized, and 6% mislocalized/lateralized. False localization/lateralization occurred in 28% of occipital and 16% of parietal seizures. Rhythmic temporal theta at ictal onset was seen exclusively in temporal lobe seizures, whereas localized repetitive epileptiform activity was highly predictive of LFLE. Seizures arising from the lateral convexity and mesial regions were differentiated by a high incidence of repetitive epileptiform activity at ictal onset in the former and rhythmic theta activity in the latter. With the exception of mesial frontal lobe epilepsy, ictal recordings are very useful in the localization/lateralization of focal seizures. Some patterns are highly accurate in localizing the epileptogenic lobe. One limitation of ictal EEG is the potential for false localization/lateralization in occipital and parietal lobe epilepsies.

  18. [A case of focal epilepsy manifesting multiple psychiatric auras].

    PubMed

    Ezura, Michinori; Kakisaka, Yosuke; Jin, Kazutaka; Kato, Kazuhiro; Iwasaki, Masaki; Fujikawa, Mayu; Aoki, Masashi; Nakasato, Nobukazu

    2015-01-01

    We present a case of epilepsy with multiple types of focal seizures that were misdiagnosed as psychiatric disorders. A 20-year-old female patient presented with a variety of episodes, including loss of consciousness, deja vu, fear, delusion of possession, violent movements, and generalized convulsions. Each of these symptoms appeared in a stereotypic manner. She was initially diagnosed with a psychiatric disorder and treated with psychoactive medications, which had no effect. Long-term video electroencephalography revealed that her episodes of violent movement with impaired consciousness and secondarily generalized seizure were epileptic events originating in the right hemisphere. High-field brain magnetic resonance imaging for detecting subtle lesions revealed bilateral lesions from periventricular nodular heterotopia. Her final diagnosis was right hemispheric focal epilepsy. Carbamazepine administration was started, which successfully controlled all seizures. The present case demonstrates the pitfall of diagnosing focal epilepsy when it presents with multiple types of psychiatric aura. Epilepsy should thus be included in differential diagnoses, considering the stereotypic nature of symptoms, to avoid misdiagnosis.

  19. Effects of adjunctive eslicarbazepine acetate on neurocognitive functioning in children with refractory focal-onset seizures.

    PubMed

    Jóźwiak, Sergiusz; Veggiotti, P; Moreira, J; Gama, H; Rocha, F; Soares-da-Silva, P

    2018-04-01

    This was a phase-II, randomized, double-blind (DB), placebo-controlled study aimed to evaluate neurocognitive effects of eslicarbazepine acetate (ESL) as adjunctive therapy in pediatric patients with refractory focal-onset seizures (FOS). Children (6-16years old) with FOS were randomized (2:1) to ESL or placebo. Treatment started at 10mg/kg/day, was up-titrated up to 30mg/kg/day (target dose), and maintained for 8weeks, followed by one-year open-label follow-up. The primary endpoint was change from baseline to the end of maintenance period in the composite Power of Attention assessed with the Cognitive Drug Research (CDR) system. Behavioral and emotional functioning and quality of life (QOL), secondary endpoints, were assessed with Child Health Questionnaire-Parent Form 50 (CHQ-PF50), Child Behavior Checklist (CBCL), and Raven's Standard Progressive Matrices (SPM). Efficacy was evaluated through changes in standardized seizure frequency (SF), responder rate, and proportion of seizure-free patients. Safety was evaluated by the incidence of treatment-emergent adverse events (TEAEs). One hundred and twenty-three patients were randomized. A noninferiority analysis failed to reject the null hypothesis that the change from baseline in the Power of Attention score in the ESL group was at least 121ms inferior to the placebo group for all age groups. The CDR scores showed no differences between placebo and ESL in Power of Attention (1868.0 vs 1759.5), Continuity of Attention (1.136 vs -1.786), Quality of Working Memory (-0.023 vs -0.024), and Speed of Memory (-263.4 vs -249.6). Nonsignificant differences between placebo and ESL were seen for CHQ-PF50, CBCL scores, and Raven's SPM. Episodic Memory Index showed significant negative effect on ESL. Efficacy results favored the ESL group (SF least square [LS] means 1.98 vs 4.29). The TEAEs had a similar incidence between treatment groups (41.0% vs 47.5%). Overall ESL did not produce statistically significant effects on

  20. Early Detection of Human Focal Seizures Based on Cortical Multiunit Activity

    PubMed Central

    Park, Yun S.; Hochberg, Leigh R.; Eskandar, Emad N.; Cash, Sydney S.; Truccolo, Wilson

    2014-01-01

    Approximately 50 million people in the world suffer from epileptic seizures. Reliable early seizure detection could bring significantly beneficial therapeutic alternatives. In recent decades, most approaches have relied on scalp EEG and intracranial EEG signals, but practical early detection for closed-loop seizure control remains challenging. In this study, we present preliminary analyses of an early detection approach based on intracortical neuronal multiunit activity (MUA) recorded from a 96-microelectrode array (MEA). The approach consists of (1) MUA detection from broadband field potentials recorded at 30 kHz by the MEA; (2) MUA feature extraction; (3) cost-sensitive support vector machine classification of ictal and interictal samples; and (4) Kalman-filtering postprocessing. MUA was here defined as the number of threshold crossing (spike counts) applied to the 300 Hz – 6 kHz bandpass filtered local field potentials in 0.1 sec time windows. MUA features explored in this study included the mean, variance, and Fano-factor, computed across the MEA channels. In addition, we used the leading eigenvalues of MUA spatial and temporal correlation matrices computed in 1-sec moving time windows. We assessed the seizure detection approach on out-of-sample data from one-participant recordings with six seizure events and 4.73-hour interictal data. The proposed MUA-based detection approach yielded a 100% sensitivity (6/6) and no false positives, and a latency of 4.17 ± 2.27 sec (mean ± SD) with respect to ECoG-identified seizure onsets. These preliminary results indicate intracortical MUA may be a useful signal for early detection of human epileptic seizures. PMID:25571313

  1. The value of magnetoencephalography for seizure-onset zone localization in magnetic resonance imaging-negative partial epilepsy

    PubMed Central

    Bouet, Romain; Delpuech, Claude; Ryvlin, Philippe; Isnard, Jean; Guenot, Marc; Bertrand, Olivier; Hammers, Alexander; Mauguière, François

    2013-01-01

    Surgical treatment of epilepsy is a challenge for patients with non-contributive brain magnetic resonance imaging. However, surgery is feasible if the seizure-onset zone is precisely delineated through intracranial electroencephalography recording. We recently described a method, volumetric imaging of epileptic spikes, to delineate the spiking volume of patients with focal epilepsy using magnetoencephalography. We postulated that the extent of the spiking volume delineated with volumetric imaging of epileptic spikes could predict the localizability of the seizure-onset zone by intracranial electroencephalography investigation and outcome of surgical treatment. Twenty-one patients with non-contributive magnetic resonance imaging findings were included. All patients underwent intracerebral electroencephalography investigation through stereotactically implanted depth electrodes (stereo-electroencephalography) and magnetoencephalography with delineation of the spiking volume using volumetric imaging of epileptic spikes. We evaluated the spatial congruence between the spiking volume determined by magnetoencephalography and the localization of the seizure-onset zone determined by stereo-electroencephalography. We also evaluated the outcome of stereo-electroencephalography and surgical treatment according to the extent of the spiking volume (focal, lateralized but non-focal or non-lateralized). For all patients, we found a spatial overlap between the seizure-onset zone and the spiking volume. For patients with a focal spiking volume, the seizure-onset zone defined by stereo-electroencephalography was clearly localized in all cases and most patients (6/7, 86%) had a good surgical outcome. Conversely, stereo-electroencephalography failed to delineate a seizure-onset zone in 57% of patients with a lateralized spiking volume, and in the two patients with bilateral spiking volume. Four of the 12 patients with non-focal spiking volumes were operated upon, none became seizure

  2. The value of magnetoencephalography for seizure-onset zone localization in magnetic resonance imaging-negative partial epilepsy.

    PubMed

    Jung, Julien; Bouet, Romain; Delpuech, Claude; Ryvlin, Philippe; Isnard, Jean; Guenot, Marc; Bertrand, Olivier; Hammers, Alexander; Mauguière, François

    2013-10-01

    Surgical treatment of epilepsy is a challenge for patients with non-contributive brain magnetic resonance imaging. However, surgery is feasible if the seizure-onset zone is precisely delineated through intracranial electroencephalography recording. We recently described a method, volumetric imaging of epileptic spikes, to delineate the spiking volume of patients with focal epilepsy using magnetoencephalography. We postulated that the extent of the spiking volume delineated with volumetric imaging of epileptic spikes could predict the localizability of the seizure-onset zone by intracranial electroencephalography investigation and outcome of surgical treatment. Twenty-one patients with non-contributive magnetic resonance imaging findings were included. All patients underwent intracerebral electroencephalography investigation through stereotactically implanted depth electrodes (stereo-electroencephalography) and magnetoencephalography with delineation of the spiking volume using volumetric imaging of epileptic spikes. We evaluated the spatial congruence between the spiking volume determined by magnetoencephalography and the localization of the seizure-onset zone determined by stereo-electroencephalography. We also evaluated the outcome of stereo-electroencephalography and surgical treatment according to the extent of the spiking volume (focal, lateralized but non-focal or non-lateralized). For all patients, we found a spatial overlap between the seizure-onset zone and the spiking volume. For patients with a focal spiking volume, the seizure-onset zone defined by stereo-electroencephalography was clearly localized in all cases and most patients (6/7, 86%) had a good surgical outcome. Conversely, stereo-electroencephalography failed to delineate a seizure-onset zone in 57% of patients with a lateralized spiking volume, and in the two patients with bilateral spiking volume. Four of the 12 patients with non-focal spiking volumes were operated upon, none became seizure

  3. Spontaneous seizures in a rat model of multiple prenatal freeze lesioning.

    PubMed

    Kamada, Takashi; Sun, Wei; Takase, Kei-Ichiro; Shigeto, Hiroshi; Suzuki, Satoshi O; Ohyagi, Yasumasa; Kira, Jun-Ichi

    2013-08-01

    Focal cortical dysplasia (FCD) is an important cause of intractable epilepsy. Previous rat studies have utilized freeze lesioning of neonatal animals to model FCD; however, such models are unable to demonstrate spontaneous seizures without seizure-provoking events. Therefore, we created an animal model with multiple FCD, produced during embryonic development, and observed whether spontaneous seizures occurred. Furthermore, we examined the relationship between FCD and epileptogenesis using immunohistochemistry. At 18 days postconception, a frozen metal probe was placed bilaterally on the scalps of Sprague-Dawley rat embryos through the uterus wall to produce multiple FCD. Electroencephalogram (EEG) and video recording were performed from postnatal day (P) 35 to P77. Brain tissues were examined immunohistochemically at P28 and P78 using semiquantitative densitometry. Eleven of 16 rats (68.8%) showed spontaneous seizures arising in the hippocampus from P47. Movement cessation followed by sniffing and mastication, culminating in wet-dog shaking, was seen during the hippocampal EEG discharges. FCD was observed in the bilateral frontoparietal lobes. The expression levels of N-methyl-d-aspartate receptor (NMDAR) subunits 1, 2A, 2B, the glutamate/aspartate transporter and the glial glutamate transporter 1 (GLT1) at FCD sites were increased at P28 and P78. There were no major histological abnormalities in the hippocampi compared with those in the cortex. However, the expression levels of NMDAR 2A and 2B were increased at P28. Levels of NMDAR1, 2A and 2B, the glutamate/aspartate transporter and GLT1 were also increased at P78. We created an animal model showing spontaneous seizures without a provoking event except for the existence of cortical dysplasia, and without a genetic or general systematic cause like MAM injection or irradiation. The seizures resembled human temporal lobe epilepsy both clinically and on EEG. Alterations in the levels of glutamatergic and GABAergic

  4. Prevalence and risk factors of seizure clusters in adult patients with epilepsy.

    PubMed

    Chen, Baibing; Choi, Hyunmi; Hirsch, Lawrence J; Katz, Austen; Legge, Alexander; Wong, Rebecca A; Jiang, Alfred; Kato, Kenneth; Buchsbaum, Richard; Detyniecki, Kamil

    2017-07-01

    In the current study, we explored the prevalence of physician-confirmed seizure clusters. We also investigated potential clinical factors associated with the occurrence of seizure clusters overall and by epilepsy type. We reviewed medical records of 4116 adult (≥16years old) outpatients with epilepsy at our centers for documentation of seizure clusters. Variables including patient demographics, epilepsy details, medical and psychiatric history, AED history, and epilepsy risk factors were then tested against history of seizure clusters. Patients were then divided into focal epilepsy, idiopathic generalized epilepsy (IGE), or symptomatic generalized epilepsy (SGE), and the same analysis was run. Overall, seizure clusters were independently associated with earlier age of seizure onset, symptomatic generalized epilepsy (SGE), central nervous system (CNS) infection, cortical dysplasia, status epilepticus, absence of 1-year seizure freedom, and having failed 2 or more AEDs (P<0.0026). Patients with SGE (27.1%) were more likely to develop seizure clusters than patients with focal epilepsy (16.3%) and IGE (7.4%; all P<0.001). Analysis by epilepsy type showed that absence of 1-year seizure freedom since starting treatment at one of our centers was associated with seizure clustering in patients across all 3 epilepsy types. In patients with SGE, clusters were associated with perinatal/congenital brain injury. In patients with focal epilepsy, clusters were associated with younger age of seizure onset, complex partial seizures, cortical dysplasia, status epilepticus, CNS infection, and having failed 2 or more AEDs. In patients with IGE, clusters were associated with presence of an aura. Only 43.5% of patients with seizure clusters were prescribed rescue medications. Patients with intractable epilepsy are at a higher risk of developing seizure clusters. Factors such as having SGE, CNS infection, cortical dysplasia, status epilepticus or an early seizure onset, can also

  5. Unilateral hemispheric memory and hippocampal neuronal density in temporal lobe epilepsy.

    PubMed

    O'Rourke, D M; Saykin, A J; Gilhool, J J; Harley, R; O'Connor, M J; Sperling, M R

    1993-04-01

    We examined the relationship of preoperative unilateral memory function and quantitative hippocampal histology in patients undergoing anterior temporal lobectomy for the treatment of complex partial seizures. Recognition memory (objects, words, figures) was assessed preoperatively for each hemisphere by the intracarotid amobarbital procedure in 23 patients (mean age at the time of operation, 30.2 yr; standard deviation, 9.2; mean age at the time of seizure onset, 12.3 yr; standard deviation, 8.6) without tumor. Memory scores were the total number of items recognized, adjusted for guessing. Histological examination of the anterior 20 to 30 mm of hippocampal tissue was accomplished in all patients. The degree of unilateral memory impairment ipsilateral to the seizure focus was significantly correlated with decreased neuronal density in the hilar (r = 0.66, P < 0.001) and dentate granule (r = 0.61, P < 0.002) regions, but not in the CA1 (r = 0.10, P = not significant) or CA2-3 (r = 0.35, P = not significant) regions. Memory performance with the contralateral hemisphere was not significantly correlated with ipsilateral hippocampal densities. These data support the role of the hippocampus in human memory and show further evidence of hippocampal subfield specificity in the relationship between memory performance and neuronal cell loss. Further studies of the dentate granule and hilar regions in relation to human memory are warranted.

  6. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009.

    PubMed

    Berg, Anne T; Berkovic, Samuel F; Brodie, Martin J; Buchhalter, Jeffrey; Cross, J Helen; van Emde Boas, Walter; Engel, Jerome; French, Jacqueline; Glauser, Tracy A; Mathern, Gary W; Moshé, Solomon L; Nordli, Douglas; Plouin, Perrine; Scheffer, Ingrid E

    2010-04-01

    The International League Against Epilepsy (ILAE) Commission on Classification and Terminology has revised concepts, terminology, and approaches for classifying seizures and forms of epilepsy. Generalized and focal are redefined for seizures as occurring in and rapidly engaging bilaterally distributed networks (generalized) and within networks limited to one hemisphere and either discretely localized or more widely distributed (focal). Classification of generalized seizures is simplified. No natural classification for focal seizures exists; focal seizures should be described according to their manifestations (e.g., dyscognitive, focal motor). The concepts of generalized and focal do not apply to electroclinical syndromes. Genetic, structural-metabolic, and unknown represent modified concepts to replace idiopathic, symptomatic, and cryptogenic. Not all epilepsies are recognized as electroclinical syndromes. Organization of forms of epilepsy is first by specificity: electroclinical syndromes, nonsyndromic epilepsies with structural-metabolic causes, and epilepsies of unknown cause. Further organization within these divisions can be accomplished in a flexible manner depending on purpose. Natural classes (e.g., specific underlying cause, age at onset, associated seizure type), or pragmatic groupings (e.g., epileptic encephalopathies, self-limited electroclinical syndromes) may serve as the basis for organizing knowledge about recognized forms of epilepsy and facilitate identification of new forms.

  7. Impaired hippocampal glucose metabolism during and after flurothyl-induced seizures in mice: Reduced phosphorylation coincides with reduced activity of pyruvate dehydrogenase.

    PubMed

    McDonald, Tanya S; Borges, Karin

    2017-07-01

    To determine changes in glucose metabolism and the enzymes involved in the hippocampus ictally and postictally in the acute mouse flurothyl seizure model. [U- 13 C]-Glucose was injected (i.p.) prior to, or following a 5 min flurothyl-induced seizure. Fifteen minutes later, mice were killed and the total metabolite levels and % 13 C enrichment were analyzed in the hippocampal formation using gas chromatography-mass spectrometry. Activities of key metabolic and antioxidant enzymes and the phosphorylation status of pyruvate dehydrogenase were measured, along with lipid peroxidation. During seizures, total lactate levels increased 1.7-fold; however, [M + 3] enrichment of both lactate and alanine were reduced by 30% and 43%, respectively, along with a 28% decrease in phosphofructokinase activity. Postictally the % 13 C enrichments of all measured tricarboxylic acid (TCA) cycle intermediates and the amino acids were reduced by 46-93%. At this time, pyruvate dehydrogenase (PDH) activity was 56% of that measured in controls, and there was a 1.9-fold increase in the phosphorylation of PDH at ser232. Phosphorylation of PDH is known to decrease its activity. Here, we show that the increase of lactate levels during flurothyl seizures is from a source other than [U- 13 C]-glucose, such as glycogen. Surprisingly, although we saw a reduction in phosphofructokinase activity during the seizure, metabolism of [U- 13 C]-glucose into the TCA cycle seemed unaffected. Similar to our recent findings in the chronic phase of the pilocarpine model, postictally the metabolism of glucose by glycolysis and the TCA cycle was impaired along with reduced PDH activity. Although this decrease in activity may be a protective mechanism to reduce oxidative stress, which is observed in the flurothyl model, ATP is critical to the recovery of ion and neurotransmitter balance and return to normal brain function. Thus we identified promising novel strategies to enhance energy metabolism and recovery from

  8. Individualized Low-Amplitude Seizure Therapy: Minimizing Current for Electroconvulsive Therapy and Magnetic Seizure Therapy.

    PubMed

    Peterchev, Angel V; Krystal, Andrew D; Rosa, Moacyr A; Lisanby, Sarah H

    2015-08-01

    Electroconvulsive therapy (ECT) at conventional current amplitudes (800-900 mA) is highly effective but carries the risk of cognitive side effects. Lowering and individualizing the current amplitude may reduce side effects by virtue of a less intense and more focal electric field exposure in the brain, but this aspect of ECT dosing is largely unexplored. Magnetic seizure therapy (MST) induces a weaker and more focal electric field than ECT; however, the pulse amplitude is not individualized and the minimum amplitude required to induce a seizure is unknown. We titrated the amplitude of long stimulus trains (500 pulses) as a means of determining the minimum current amplitude required to induce a seizure with ECT (bilateral, right unilateral, bifrontal, and frontomedial electrode placements) and MST (round coil on vertex) in nonhuman primates. Furthermore, we investigated a novel method of predicting this amplitude-titrated seizure threshold (ST) by a non-convulsive measurement of motor threshold (MT) using single pulses delivered through the ECT electrodes or MST coil. Average STs were substantially lower than conventional pulse amplitudes (112-174 mA for ECT and 37.4% of maximum device amplitude for MST). ST was more variable in ECT than in MST. MT explained 63% of the ST variance and is hence the strongest known predictor of ST. These results indicate that seizures can be induced with less intense electric fields than conventional ECT that may be safer; efficacy and side effects should be evaluated in clinical studies. MT measurement could be a faster and safer alternative to empirical ST titration for ECT and MST.

  9. Acute seizures in cerebral venous sinus thrombosis: What predicts it?

    PubMed

    Mahale, Rohan; Mehta, Anish; John, Aju Abraham; Buddaraju, Kiran; Shankar, Abhinandan K; Javali, Mahendra; Srinivasa, Rangasetty

    2016-07-01

    Seizures are the presenting feature of cerebral venous sinus thrombosis (CVST) in 12-31.9% of patients. 44.3% of patients have seizures in the early stage of the disease. Acute seizures (AS), refers to seizures which take place before the diagnosis or during the first 2 weeks afterward. To report the predictors of acute seizures in cerebral venous sinus thrombosis (CVST). 100 patients with CVST were included in the study. The occurrence of acute seizures was noted. The predictors of acute seizure were evaluated by univariate analysis including the demographic (gender, age), clinical (headache, focal neurological deficit, papilloedema, GCS score), type and number of risk factors, MRI findings (Type of lesion: hemorrhagic infarction or hematoma, location of lesion) and MRV findings (superficial or deep sinus, cortical veins). A total of 46 patients had acute seizures. On univariate analysis, altered mental status (p<0.001), paresis (p=0.03), GCS score <8 (p=0.009), hemorrhagic infarct on imaging (p=0.04), involvement of frontal lobe (p=0.02), superior sagittal sinus (p=0.008), and high D-dimer levels (p=0.03) were significantly associated with acute seizure. On multivariate analysis, the hemorrhagic infarct on MRI and high D-dimer was independently predictive for early seizure. The predictive factors for the acute seizures are altered mental status (GCS<8), focal deficits, hemorrhagic infarct, involvement of frontal lobe and superior sagittal sinus with high D-dimer levels. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Allosteric modulation of sigma-1 receptors elicits anti-seizure activities.

    PubMed

    Guo, Lin; Chen, Yanke; Zhao, Rui; Wang, Guanghui; Friedman, Eitan; Zhang, Ao; Zhen, Xuechu

    2015-08-01

    Application of orthosteric sigma-1 receptor agonists as anti-seizure drugs has been hindered by questionable efficacy and potential adverse effects. Here, we have investigated the anti-seizure effects of the novel and potent allosteric modulator of sigma-1 receptors, SKF83959 and its derivative SOMCL-668 (3-methyl-phenyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ol). The anti-seizure effects of SKF83959 were investigated in three mouse models, maximal electroshock seizures, pentylenetetrazole-induced convulsions and kainic acid-induced 'status epilepticus'. Also, in rats, the cortical epileptiform activity induced by topical application of picrotoxin was recorded in electrocorticograms. In rat hippocampal brain slices, effects of the drugs on the high potassium-evoked epileptiform local field potentials were studied. Anti-seizure activities of SOMCL-668, a newly developed sigma-1 receptor selective allosteric modulator, were also investigated. SKF83959 (20, 40 mg·kg(-1) ) exhibited anti -seizure actitity in the three mouse models and reduced the cortical epileptiform activity without alteration of spontaneous motor activity and motor coordination. These effects were blocked by the sigma-1 receptor antagonist BD1047, but not the dopamine D1 receptor antagonist SCH23390. SKF83959 alone did not directly inhibit the epileptiform firing of CA3 neurons induced by high potassium in hippocampal slices, but did potentiate inhibition by the orthosteric sigma-1 receptor agonist SKF10047. Lastly, a selective sigma-1 receptor allosteric modulator SOMCL-668, which does not bind to dopamine receptors, exerted similar anti-seizure activities. SKF83959 and SOMCL-668 displayed anti-seizure activities, indicating that allosteric modulation of sigma-1 receptors may provide a novel approach for discovering new anti-seizure drugs. © 2015 The British Pharmacological Society.

  11. The role of histopathologic subtype in the setting of hippocampal sclerosis-associated mesial temporal lobe epilepsy.

    PubMed

    Gales, Jordan M; Jehi, Lara; Nowacki, Amy; Prayson, Richard A

    2017-05-01

    Hippocampal sclerosis (HS) and focal cortical dysplasia (FCD) are among the most common neuropathological findings in those undergoing surgery for refractory mesial temporal lobe epilepsy. Existing data regarding differences among the most recent International League Against Epilepsy (ILAE) HS subtypes remain limited. This study sought to characterize the roles of HS subtype and coexistent FCD. Epilepsy surgery pathologic specimens in 307 cases of temporal lobe epilepsy with HS were reviewed (mean age±SD, 37±15years; 56% women). HS and coexistent FCD were classified according to ILAE guidelines. Medical records were reviewed for data on seizure recurrence and seizure burden (clinical follow-up mean duration ± SD, 5±4years). Cases of typical HS (ILAE type I) predominated (ILAE type Ia: 41%, Ib: 47%, II: 11%, and III: 0.7%]. The HS subtypes shared similar demographic and etiologic characteristics, as well as associated pathology and postoperative seizure outcomes. Individuals with type Ib HS were more likely to remain seizure free at long-term follow-up when compared with other subtypes, and they had a later age of seizure onset. Two hundred forty-three cases (79%) demonstrated FCD within the adjacent temporal lobe. Its presence was associated with a significantly decreased risk of seizure recurrence (P=.02). When present, FCD was predominantly type I (98%). HS subtype does not appear to affect epilepsy surgery outcomes despite some clinical differences between the subgroups. FCD is often observed in association with HS in mesial temporal lobe epilepsy; the finding of FCD was associated with better postoperative outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Clinical presentation of neurocysticercosis-related epilepsy.

    PubMed

    Duque, Kevin R; Burneo, Jorge G

    2017-11-01

    Neurocysticercosis (NCC) is the most common parasitic infection of the central nervous system and a major risk factor for seizures and epilepsy. Seizure types in NCC vary largely across studies and seizure semiology is poorly understood. We discuss here the studies regarding seizure types and seizure semiology in NCC, and examine the clinical presentation in patients with NCC and drug-resistant epilepsy. We also provide evidence of the role of MRI and EEG in the diagnosis of NCC-related epilepsy. Focal seizures are reported in 60-90% of patients with NCC-related epilepsy, and around 90% of all seizures registered prospectively are focal not evolving to bilateral tonic-clonic seizures. A great number of cases suggest that seizure semiology is topographically related to NCC lesions. Patients with hippocampal sclerosis and NCC have different clinical and neurophysiological characteristics than those with hippocampal sclerosis alone. Different MRI protocols have allowed to better differentiate NCC from other etiologies. Lesions' stages might account on the chances of finding an interictal epileptiform discharge. Studies pursuing the seizure onset in patients with NCC are lacking and they are specially needed to determine both whether the reported events of individual cases are seizures, and whether they are related to the NCC lesion or lesions. This article is part of a Special Issue entitled "Neurocysticercosis and Epilepsy". Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Effects of hypoxia-induced neonatal seizures on acute hippocampal injury and later-life seizure susceptibility and anxiety-related behavior in mice.

    PubMed

    Rodriguez-Alvarez, Natalia; Jimenez-Mateos, Eva M; Dunleavy, Mark; Waddington, John L; Boylan, Geraldine B; Henshall, David C

    2015-11-01

    Seizures are common during the neonatal period, often due to hypoxic-ischemic encephalopathy and may contribute to acute brain injury and the subsequent development of cognitive deficits and childhood epilepsy. Here we explored short- and long-term consequences of neonatal hypoxia-induced seizures in 7 day old C57BL/6J mice. Seizure activity, molecular markers of hypoxia and histological injury were investigated acutely after hypoxia and response to chemoconvulsants and animal behaviour was explored at adulthood. Hypoxia was induced by exposing pups to 5% oxygen for 15 min (global hypoxia). Electrographically defined seizures with behavioral correlates occurred in 95% of these animals and seizures persisted for many minutes after restitution of normoxia. There was minimal morbidity or mortality. Pre- or post-hypoxia injection of phenobarbital (50mg/kg) had limited efficacy at suppressing seizures. The hippocampus from neonatal hypoxia-seizure mice displayed increased expression of vascular endothelial growth factor and the immediate early gene c-fos, minimal histological evidence of cell injury and activation of caspase-3 in scattered neurons. Behavioral analysis of mice five weeks after hypoxia-induced seizures detected novel anxiety-related and other behaviors, while performance in a spatial memory test was similar to controls. Seizure threshold tests with kainic acid at six weeks revealed that mice previously subject to neonatal hypoxia-induced seizures developed earlier, more frequent and longer-duration seizures. This study defines a set of electro-clinical, molecular, pharmacological and behavioral consequences of hypoxia-induced seizures that indicate short- and long-term deleterious outcomes and may be a useful model to investigate the pathophysiology and treatment of neonatal seizures in humans. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Aspirin attenuates spontaneous recurrent seizures in the chronically epileptic mice.

    PubMed

    Zhu, Kun; Hu, Ming; Yuan, Bo; Liu, Jian-Xin; Liu, Yong

    2017-08-01

    Neuroinflammatory processes are pathologic hallmarks of both experimental and human epilepsy, and could be implicated in the neuronal hyperexcitability. Aspirin represents one of the non-selective nonsteroidal anti-inflammatory drugs with fewer side effects in long-term application. This study was carried out to assess the anti-epileptic effects of aspirin when administered during the chronic stage of temporal lobe epilepsy [TLE] in mice. The alteration of hippocampal neurogenesis was also examined for raising a possible mechanism underlying the protective effect of anti-inflammatory treatment in the TLE. Two months after pilocarpine-induced status epilepticus, the chronically epileptic mice were treated with aspirin (20 mg, 60 mg or 80 mg/kg) once a day for 10 weeks. Spontaneous recurrent seizures were monitored by video camera for 2 weeks. To evaluate the profile of hippocampal neurogenesis, the newly generated cells in the dentate gyrus were labeled by the proliferation marker BrdU. The newborn neurons that extended axons to CA3 area were visualized by cholera toxin B subunit retrograde tracing. Administration of aspirin with a dosage of 60 mg or 80 mg/kg initiated at 2 months after pilocarpine-induced status epilepticus significantly reduced the frequency and duration of spontaneous recurrent seizures. Aspirin treatment also increased the number of newborn neurons with anatomic integration through improving the survival of the newly generated cells. Aspirin treatment during the chronic stage of TLE could attenuate the spontaneous recurrent seizures in mice. Promotion of hippocampal neurogenesis and inhibition of COX-PGE2 pathway might partly contribute to this anti-epileptic effect. Highlights • Aspirin attenuates spontaneous recurrent seizures of chronically epileptic mice • Aspirin increases neurogenesis of chronically epileptic hippocampus by improving the survival of newly generated cells • Promotion of hippocampal neurogenesis and inhibition

  15. Individualized Low-Amplitude Seizure Therapy: Minimizing Current for Electroconvulsive Therapy and Magnetic Seizure Therapy

    PubMed Central

    Peterchev, Angel V; Krystal, Andrew D; Rosa, Moacyr A; Lisanby, Sarah H

    2015-01-01

    Electroconvulsive therapy (ECT) at conventional current amplitudes (800–900 mA) is highly effective but carries the risk of cognitive side effects. Lowering and individualizing the current amplitude may reduce side effects by virtue of a less intense and more focal electric field exposure in the brain, but this aspect of ECT dosing is largely unexplored. Magnetic seizure therapy (MST) induces a weaker and more focal electric field than ECT; however, the pulse amplitude is not individualized and the minimum amplitude required to induce a seizure is unknown. We titrated the amplitude of long stimulus trains (500 pulses) as a means of determining the minimum current amplitude required to induce a seizure with ECT (bilateral, right unilateral, bifrontal, and frontomedial electrode placements) and MST (round coil on vertex) in nonhuman primates. Furthermore, we investigated a novel method of predicting this amplitude-titrated seizure threshold (ST) by a non-convulsive measurement of motor threshold (MT) using single pulses delivered through the ECT electrodes or MST coil. Average STs were substantially lower than conventional pulse amplitudes (112–174 mA for ECT and 37.4% of maximum device amplitude for MST). ST was more variable in ECT than in MST. MT explained 63% of the ST variance and is hence the strongest known predictor of ST. These results indicate that seizures can be induced with less intense electric fields than conventional ECT that may be safer; efficacy and side effects should be evaluated in clinical studies. MT measurement could be a faster and safer alternative to empirical ST titration for ECT and MST. PMID:25920013

  16. Low Frequency Stimulation Decreases Seizure Activity in a Mutation Model of Epilepsy

    PubMed Central

    Kile, Kara Buehrer; Tian, Nan; Durand, Dominique M.

    2013-01-01

    Summary Purpose To investigate brain electrical activity in Q54 mice that display spontaneous seizures because of a gain-of-function mutation of the Scn2a sodium channel gene, and to evaluate the efficacy of low frequency deep brain stimulation (DBS) for seizure frequency reduction. Methods EEG, EMG, and hippocampal deep electrodes were implanted into Q54 mice expressing an epileptic phenotype (n = 6). Chronic six channel recordings (wideband, 0.1–300 Hz) were stored 24 hours a day for more than 12 days. Low Frequency stimulation (LFS) (3Hz, square wave, biphasic, 100μs, 400μA) was applied to the ventral hippocampal commisure (VHC) in alternating five minute cycles (on or off) 24 hours a day for a period of four days. Results LFS (3Hz) resulted in a significant reduction in seizure frequency and duration (21% and 35%, p<0.05), when applied to the VHC of epileptic Q54 mice (n = 6). Seizure frequency was not directly affected by stimulation state (“on” versus “off”). Conclusion LFS applied at a frequency of 3Hz significantly reduced seizure frequency and duration in the Q54 model. Furthermore, the reduction of seizure frequency and duration by LFS was not immediate but had a delayed and lasting effect, supporting complex, indirect mechanisms of action. PMID:20659150

  17. Loss of hippocampal serine protease BSP1/neuropsin predisposes to global seizure activity.

    PubMed

    Davies, B; Kearns, I R; Ure, J; Davies, C H; Lathe, R

    2001-09-15

    Serine proteases in the adult CNS contribute both to activity-dependent structural changes accompanying learning and to the regulation of excitotoxic cell death. Brain serine protease 1 (BSP1)/neuropsin is a trypsin-like serine protease exclusively expressed, within the CNS, in the hippocampus and associated limbic structures. To explore the role of this enzyme, we have used gene targeting to disrupt this gene in mice. Mutant mice were viable and overtly normal; they displayed normal hippocampal long-term synaptic potentiation (LTP) and exhibited no deficits in spatial navigation (water maze). Nevertheless, electrophysiological studies revealed that the hippocampus of mice lacking this specifically expressed protease possessed an increased susceptibility for hyperexcitability (polyspiking) in response to repetitive afferent stimulation. Furthermore, seizure activity on kainic acid administration was markedly increased in mutant mice and was accompanied by heightened immediate early gene (c-fos) expression throughout the brain. In view of the regional selectivity of BSP1/neuropsin brain expression, the observed phenotype may selectively reflect limbic function, further implicating the hippocampus and amygdala in controlling cortical activation. Within the hippocampus, our data suggest that BSP1/neuropsin, unlike other serine proteases, has little effect on physiological synaptic remodeling and instead plays a role in limiting neuronal hyperexcitability induced by epileptogenic insult.

  18. Are YouTube seizure videos misleading? Neurologists do not always agree.

    PubMed

    Brna, P M; Dooley, J M; Esser, M J; Perry, M S; Gordon, K E

    2013-11-01

    The internet has become the first stop for the public and patients to seek health-related information. Video-sharing websites are particularly important sources of information for those seeking answers about seizures and epilepsy. Because of the widespread popularity of YouTube, we sought to explore whether a seizure diagnosis and classification could reliably be applied. All videos related to "seizures" were reviewed, and irrelevant videos were excluded. The remaining 162 nonduplicate videos were analyzed by 4 independent pediatric neurologists who classified the events as epilepsy seizures, nonepileptic seizures, or indeterminate. Videos designated as epilepsy seizures were then classified into focal, generalized, or unclassified. At least 3 of the 4 reviewers agreed that 35% of the videos showed that the events were "epilepsy seizures", at least 3 of the 4 reviewers agreed that 28% of the videos demonstrated that the events were "nonepileptic seizures", and there was good agreement that 7% of the videos showed that the event was "indeterminate". Overall, interrater agreement was moderate at k=0.57 for epilepsy seizures and k=0.43 for nonepileptic seizures. For seizure classification, reviewer agreement was greatest for "generalized seizures" (k=0.45) and intermediate for "focal seizures" (k=0.27), and there was no agreement for unclassified events (k=0.026, p=0.2). Overall, neurology reviewer agreement suggests that only approximately one-third of the videos designated as "seizures" on the most popular video-sharing website, YouTube, definitely depict a seizure. Caution should be exercised in the use of such online video media for accessing educational or self-diagnosis aids for seizures. © 2013.

  19. Automatic multimodal detection for long-term seizure documentation in epilepsy.

    PubMed

    Fürbass, F; Kampusch, S; Kaniusas, E; Koren, J; Pirker, S; Hopfengärtner, R; Stefan, H; Kluge, T; Baumgartner, C

    2017-08-01

    This study investigated sensitivity and false detection rate of a multimodal automatic seizure detection algorithm and the applicability to reduced electrode montages for long-term seizure documentation in epilepsy patients. An automatic seizure detection algorithm based on EEG, EMG, and ECG signals was developed. EEG/ECG recordings of 92 patients from two epilepsy monitoring units including 494 seizures were used to assess detection performance. EMG data were extracted by bandpass filtering of EEG signals. Sensitivity and false detection rate were evaluated for each signal modality and for reduced electrode montages. All focal seizures evolving to bilateral tonic-clonic (BTCS, n=50) and 89% of focal seizures (FS, n=139) were detected. Average sensitivity in temporal lobe epilepsy (TLE) patients was 94% and 74% in extratemporal lobe epilepsy (XTLE) patients. Overall detection sensitivity was 86%. Average false detection rate was 12.8 false detections in 24h (FD/24h) for TLE and 22 FD/24h in XTLE patients. Utilization of 8 frontal and temporal electrodes reduced average sensitivity from 86% to 81%. Our automatic multimodal seizure detection algorithm shows high sensitivity with full and reduced electrode montages. Evaluation of different signal modalities and electrode montages paces the way for semi-automatic seizure documentation systems. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  20. Neuroprotective Effect of Uncaria rhynchophylla in Kainic Acid-Induced Epileptic Seizures by Modulating Hippocampal Mossy Fiber Sprouting, Neuron Survival, Astrocyte Proliferation, and S100B Expression.

    PubMed

    Liu, Chung-Hsiang; Lin, Yi-Wen; Tang, Nou-Ying; Liu, Hsu-Jan; Hsieh, Ching-Liang

    2012-01-01

    Uncaria rhynchophylla (UR), which is a traditional Chinese medicine, has anticonvulsive effect in our previous studies, and the cellular mechanisms behind this are still little known. Because of this, we wanted to determine the importance of the role of UR on kainic acid- (KA-) induced epilepsy. Oral UR for 6 weeks can successfully attenuate the onset of epileptic seizure in animal tests. Hippocampal mossy fiber sprouting dramatically decreased, while neuronal survival increased with UR treatment in hippocampal CA1 and CA3 areas. Furthermore, oral UR for 6 weeks significantly attenuated the overexpression of astrocyte proliferation and S100B proteins but not γ-aminobutyric acid A (GABA(A)) receptors. These results indicate that oral UR for 6 weeks can successfully attenuate mossy fiber sprouting, astrocyte proliferation, and S100B protein overexpression and increase neuronal survival in KA-induced epileptic rat hippocampus.

  1. Temporal epilepsy seizures monitoring and prediction using cross-correlation and chaos theory.

    PubMed

    Haddad, Tahar; Ben-Hamida, Naim; Talbi, Larbi; Lakhssassi, Ahmed; Aouini, Sadok

    2014-01-01

    Temporal seizures due to hippocampal origins are very common among epileptic patients. Presented is a novel seizure prediction approach employing correlation and chaos theories. The early identification of seizure signature allows for various preventive measures to be undertaken. Electro-encephalography signals are spectrally broken down into the following sub-bands: delta; theta; alpha; beta; and gamma. The proposed approach consists of observing a high correlation level between any pair of electrodes for the lower frequencies and a decrease in the Lyapunov index (chaos or entropy) for the higher frequencies. Power spectral density and statistical analysis tools were used to determine threshold levels for the lower frequencies. After studying all five sub-bands, the analysis has revealed that the seizure signature can be extracted from the delta band and the high frequencies. High frequencies are defined as both the gamma band and the ripples occurring within the 60-120 Hz sub-band. To validate the proposed approach, six patients from both sexes and various age groups with temporal epilepsies originating from the hippocampal area were studied using the Freiburg database. An average seizure prediction of 30 min, an anticipation accuracy of 72%, and a false-positive rate of 0% were accomplished throughout 200 h of recording time.

  2. Tiagabine in clinical practice: effects on seizure control and behavior.

    PubMed

    Vossler, David G; Morris, George L; Harden, Cynthia L; Montouris, Georgia; Faught, Edward; Kanner, Andres M; Fix, Aaron; French, Jacqueline A

    2013-08-01

    Preapproval randomized controlled trials of antiepileptic drugs provide data in limited patient groups. We assessed the side effect and seizure reduction profile of tiagabine (TGB) in typical clinical practice. Investigators recorded adverse effect (AE), seizure, and assessment-of-benefit data prospectively in sequential patients treated open label with TGB. Two hundred ninety-two patients (39 children) were enrolled to be treated long term with TGB. Seizure types were focal-onset (86%), generalized-onset (12%), both focal- and generalized-onset (0.3%), and multiple associated with Lennox-Gastaut Syndrome (2%). Two hundred thirty-one received at least one dose of TGB (median = 28 mg/day) and had follow-up seizure or AE data reported. Common AEs were fatigue, dizziness, psychomotor slowing, ataxia, gastrointestinal upset, weight change, insomnia, and "others" (mostly behavioral). Serious AEs occurred in 19 patients: behavioral effects (n = 12), status epilepticus (n = 3), others (n = 3), and sudden unexplained death (n = 1). No patients experienced suicidal ideation/behavior, rash, nephrolithiasis, or organ failure. Seizure outcomes were seizure freedom (5%), ≥75% reduction (12%), ≥50% reduction (23%), and increased number of seizures (17%), or new seizure type (1%). Behavioral AEs occurred in a larger proportion of patients compared to those reported in TGB preapproval randomized controlled trials. A moderate percentage of patients had a meaningful reduction in seizure frequency. In clinical practice, TGB remains a useful antiepileptic drug. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Afebrile seizure subsequent to initial febrile seizure.

    PubMed

    Fallah, Razieh; Razieh, Fallah; Akhavan Karbasi, Sedighah; Sedighah, Akhavan Karbasi; Golestan, Motahhareh; Motahhareh, Golestan

    2012-05-01

    Febrile seizure (FS) is the most common paediatric neurological problem. The purpose of this study was to determine the frequency of afebrile seizures subsequent to FS in children with initial FS and to evaluate its risk factors. A prospective study was conducted on all children (age 6 months to 6 years) referred with initial FS to the Shahid Sadoughi Hospital, Yazd, Iran, between August 2004 and March 2006, who were followed up for at least 15 months for the occurrence of subsequent afebrile seizures. 161 boys and 120 girls (mean age 2.12 ± 1.33 years) were followed up for 34.1 ± 7.8 months. 87 (31%) patients had complex FS and 19 (6.7%) patients had subsequent afebrile seizure, with a mean occurrence time of 10.6 ± 6.4 months. Univariate analysis using chi-square test showed that initial FS within one hour of developing fever (p = 0.0001), neurodevelopmental delay (p = 0.0001), family history of epilepsy (p = 0.0001), recurrent FS (p = 0.003) and focal FS (p = 0.04) were risk factors for subsequent afebrile seizure. On multivariate analysis, neurodevelopmental delay (odds ratio [OR] 2.6, 95% confidence interval [CI] 2.3-3.4), initial FS within one hour of developing fever (OR 1.7, 95% CI 1.2-2.1) and family history of epilepsy (OR 1.5, 95% CI 1.1-1.9) were significant factors. Special attention should be paid to children with FS during history-taking and developmental assessments to identify high-risk patients and those who might need prophylactic anticonvulsants.

  4. [Effects and consequence of recurrent seizures of neonatal rat on the hippocampal neurogenesis].

    PubMed

    Shi, Xiu-yu; Wang, Ji-wen; Sun, Ruo-peng

    2006-04-01

    Seizures occur more frequently in the neonatal period than at any other time in life. A controversy which has been debated for the recent years is whether recurrent neonatal seizures can lead to long-term adverse consequences or are simply a reflection of underlying brain dysfunction and are not intrinsically harmful. Despite numerous clinical observations showed that seizures may be detrimental to the developing brain, the pathological mechanism has not yet been completely understood. The goal of this study was to investigate what effect was induced by recurrent seizures in neonatal rats on dentate granule cell neurogenesis. Sixty-four neonatal Wistar rats were randomly divided into seizure group (n = 40) and control group (n = 24). The rats of seizure group were subjected to three times of pilocarpine injections intraperitonealy at postnatal day 1 (P1), 4 (P4) and 7 (P7). Neonatal rats of the control group were given saline injection (i.p.) at the same time points. The rat were sacrificed separately at the next four time points: immediately after the third seizure (P7), the fourth day after the seizure (P11), the fourteenth day (P21) and the forty fifth day (P52), corresponding control group rats were killed accordingly. The rats in both seizure and control groups were given bromodeoxyuridine (BrdU) injection 36 hours before sacrifice to indicate newly generated cells. Brain tissue sections were prepared and subjected to Nissl staining for neuronal loss, by BrdU labeling for cell proliferation and by BrdU + NF200 (neurofilament 200) double labeling for the identification of the newly formed cells. The numbers of BrdU-labeled cells were age-dependent in the control group, decreased with age, and their morphorlogy and distribution changed (P < 0.01). BrdU-labeled cells decreased significantly in the seizure group compared with the matched controls at P7 and P11 (P < 0.01), while at P21 there was no significant difficence between the two groups. On the contrary, Brd

  5. Seizure Prediction and its Applications

    PubMed Central

    Iasemidis, Leon D.

    2011-01-01

    Epilepsy is characterized by intermittent, paroxysmal, hypersynchronous electrical activity, that may remain localized and/or spread and severely disrupt the brain’s normal multi-task and multi-processing function. Epileptic seizures are the hallmarks of such activity and had been considered unpredictable. It is only recently that research on the dynamics of seizure generation by analysis of the brain’s electrographic activity (EEG) has shed ample light on the predictability of seizures, and illuminated the way to automatic, prospective, long-term prediction of seizures. The ability to issue warnings in real time of impending seizures (e.g., tens of minutes prior to seizure occurrence in the case of focal epilepsy), may lead to novel diagnostic tools and treatments for epilepsy. Applications may range from a simple warning to the patient, in order to avert seizure-associated injuries, to intervention by automatic timely administration of an appropriate stimulus, for example of a chemical nature like an anti-epileptic drug (AED), electromagnetic nature like vagus nerve stimulation (VNS), deep brain stimulation (DBS), transcranial direct current (TDC) or transcranial magnetic stimulation (TMS), and/or of another nature (e.g., ultrasonic, cryogenic, biofeedback operant conditioning). It is thus expected that seizure prediction could readily become an integral part of the treatment of epilepsy through neuromodulation, especially in the new generation of closed-loop seizure control systems. PMID:21939848

  6. The Association Between Neurocysticercosis and Hippocampal Atrophy is Related to Age

    PubMed Central

    Del Brutto, Oscar H.; Issa, Naoum P.; Salgado, Perla; Del Brutto, Victor J.; Zambrano, Mauricio; Lama, Julio; García, Héctor H.

    2017-01-01

    Neurocysticercosis (NCC) has been associated with hippocampal atrophy, but the prevalence and pathogenic mechanisms implicated in this relationship are unknown. Using a population-based, case–control study design, residents in a rural village (Atahualpa) aged ≥ 40 years with calcified NCC were identified as cases and paired to NCC-free individuals (control subjects) matched by age, sex, and level of education. Cases and control subjects underwent magnetic resonance imaging for hippocampal rating according to the Scheltens' scale for medial temporal atrophy and were interviewed to identify those with a clinical seizure disorder. The prevalence of hippocampal atrophy was compared between cases and control subjects by the use of the McNemar's test for correlated proportions. Seventy-five individuals with calcified NCC and their matched control subjects were included in the analysis. Hippocampal atrophy was noted in 26 (34.7%) cases and nine (12%) control subjects (odds ratio: 4.4; 95% confidence interval: 1.6–14.9, P < 0.0021). Stratification of pairs according to tertiles of age revealed an age-related trend in this association, which became significant only in those aged ≥ 68 years (P = 0.027). Only five cases and one control had recurrent seizures (P = 0.221); three of these five cases had hippocampal atrophy, and the single control subject had normal hippocampi. This study confirms an association between NCC and hippocampal atrophy, and shows that this association is stronger in older age groups. This suggests that NCC-related hippocampal atrophy takes a long time to develop. PMID:28077750

  7. Cytidine 5'-diphosphocholine (CDP-choline) adversely effects on pilocarpine seizure-induced hippocampal neuronal death.

    PubMed

    Kim, Jin Hee; Lee, Dong Won; Choi, Bo Young; Sohn, Min; Lee, Song Hee; Choi, Hui Chul; Song, Hong Ki; Suh, Sang Won

    2015-01-21

    Citicoline (CDP-choline; cytidine 5'-diphosphocholine) is an important intermediate in the biosynthesis of cell membrane phospholipids. Citicoline serves as a choline donor in the biosynthetic pathways of acetylcholine and neuronal membrane phospholipids, mainly phosphatidylcholine. The ability of citicoline to reverse neuronal injury has been tested in animal models of cerebral ischemia and clinical trials have been performed in stroke patients. However, no studies have examined the effect of citicoline on seizure-induced neuronal death. To clarify the potential therapeutic effects of citicoline on seizure-induced neuronal death, we used an animal model of pilocarpine-induced epilepsy. Temporal lobe epilepsy (TLE) was induced by intraperitoneal injection of pilocarpine (25mg/kg) in adult male rats. Citicoline (100 or 300 mg/kg) was injected into the intraperitoneal space two hours after seizure onset and a second injection was performed 24h after the seizure. Citicoline was injected once per day for one week after pilocarpine- or kainate-induced seizure. Neuronal injury and microglial activation were evaluated at 1 week post-seizure. Surprisingly, rather than offering protection, citicoline treatment actually enhanced seizure-induced neuronal death and microglial activation in the hippocampus compared to vehicle treated controls. Citicoline administration after seizure-induction increased immunoglobulin leakage via BBB disruption in the hippocampus compared with the vehicle-only group. To clarify if this adverse effect of citicoline is generalizable across alternative seizure models, we induced seizure by kainate injection (10mg/kg, i.p.) and then injected citicoline as in pilocarpine-induced seizure. We found that citicoline did not modulate kainate seizure-induced neuronal death, BBB disruption or microglial activation. These results suggest that citicoline may not have neuroprotective effects after seizure and that clinical application of citicoline after

  8. Reducing premature KCC2 expression rescues seizure susceptibility and spine morphology in atypical febrile seizures.

    PubMed

    Awad, Patricia N; Sanon, Nathalie T; Chattopadhyaya, Bidisha; Carriço, Josianne Nunes; Ouardouz, Mohamed; Gagné, Jonathan; Duss, Sandra; Wolf, Daniele; Desgent, Sébastien; Cancedda, Laura; Carmant, Lionel; Di Cristo, Graziella

    2016-07-01

    Atypical febrile seizures are considered a risk factor for epilepsy onset and cognitive impairments later in life. Patients with temporal lobe epilepsy and a history of atypical febrile seizures often carry a cortical malformation. This association has led to the hypothesis that the presence of a cortical dysplasia exacerbates febrile seizures in infancy, in turn increasing the risk for neurological sequelae. The mechanisms linking these events are currently poorly understood. Potassium-chloride cotransporter KCC2 affects several aspects of neuronal circuit development and function, by modulating GABAergic transmission and excitatory synapse formation. Recent data suggest that KCC2 downregulation contributes to seizure generation in the epileptic adult brain, but its role in the developing brain is still controversial. In a rodent model of atypical febrile seizures, combining a cortical dysplasia and hyperthermia-induced seizures (LHS rats), we found a premature and sustained increase in KCC2 protein levels, accompanied by a negative shift of the reversal potential of GABA. In parallel, we observed a significant reduction in dendritic spine size and mEPSC amplitude in CA1 pyramidal neurons, accompanied by spatial memory deficits. To investigate whether KCC2 premature overexpression plays a role in seizure susceptibility and synaptic alterations, we reduced KCC2 expression selectively in hippocampal pyramidal neurons by in utero electroporation of shRNA. Remarkably, KCC2 shRNA-electroporated LHS rats show reduced hyperthermia-induced seizure susceptibility, while dendritic spine size deficits were rescued. Our findings demonstrate that KCC2 overexpression in a compromised developing brain increases febrile seizure susceptibility and contribute to dendritic spine alterations. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Controlling stimulation strength and focality in electroconvulsive therapy via current amplitude and electrode size and spacing: comparison with magnetic seizure therapy.

    PubMed

    Deng, Zhi-De; Lisanby, Sarah H; Peterchev, Angel V

    2013-12-01

    Understanding the relationship between the stimulus parameters of electroconvulsive therapy (ECT) and the electric field characteristics could guide studies on improving risk/benefit ratio. We aimed to determine the effect of current amplitude and electrode size and spacing on the ECT electric field characteristics, compare ECT focality with magnetic seizure therapy (MST), and evaluate stimulus individualization by current amplitude adjustment. Electroconvulsive therapy and double-cone-coil MST electric field was simulated in a 5-shell spherical human head model. A range of ECT electrode diameters (2-5 cm), spacing (1-25 cm), and current amplitudes (0-900 mA) was explored. The head model parameters were varied to examine the stimulus current adjustment required to compensate for interindividual anatomical differences. By reducing the electrode size, spacing, and current, the ECT electric field can be more focal and superficial without increasing scalp current density. By appropriately adjusting the electrode configuration and current, the ECT electric field characteristics can be made to approximate those of MST within 15%. Most electric field characteristics in ECT are more sensitive to head anatomy variation than in MST, especially for close electrode spacing. Nevertheless, ECT current amplitude adjustment of less than 70% can compensate for interindividual anatomical variability. The strength and focality of ECT can be varied over a wide range by adjusting the electrode size, spacing, and current. If desirable, ECT can be made as focal as MST while using simpler stimulation equipment. Current amplitude individualization can compensate for interindividual anatomical variability.

  10. Cracking Down on Inhibition: Selective Removal of GABAergic Interneurons from Hippocampal Networks

    PubMed Central

    Antonucci, Flavia; Alpár, Alán; Kacza, Johannes; Caleo, Matteo; Verderio, Claudia; Giani, Alice; Martens, Henrik; Chaudhry, Farrukh A.; Allegra, Manuela; Grosche, Jens; Michalski, Dominik; Erck, Christian; Hoffmann, Anke; Härtig, Wolfgang

    2012-01-01

    Inhibitory (GABAergic) interneurons entrain assemblies of excitatory principal neurons to orchestrate information processing in the hippocampus. Disrupting the dynamic recruitment as well as the temporally precise activity of interneurons in hippocampal circuitries can manifest in epileptiform seizures, and impact specific behavioral traits. Despite the importance of GABAergic interneurons during information encoding in the brain, experimental tools to selectively manipulate GABAergic neurotransmission are limited. Here, we report the selective elimination of GABAergic interneurons by a ribosome inactivation approach through delivery of saporin-conjugated anti-vesicular GABA transporter antibodies (SAVAs) in vitro as well as in the mouse and rat hippocampus in vivo. We demonstrate the selective loss of GABAergic—but not glutamatergic—synapses, reduced GABA release, and a shift in excitation/inhibition balance in mixed cultures of hippocampal neurons exposed to SAVAs. We also show the focal and indiscriminate loss of calbindin+, calretinin+, parvalbumin/system A transporter 1+, somatostatin+, vesicular glutamate transporter 3 (VGLUT3)/cholecystokinin/CB1 cannabinoid receptor+ and neuropeptide Y+ local-circuit interneurons upon SAVA microlesions to the CA1 subfield of the rodent hippocampus, with interneuron debris phagocytosed by infiltrating microglia. SAVA microlesions did not affect VGLUT1+ excitatory afferents. Yet SAVA-induced rearrangement of the hippocampal circuitry triggered network hyperexcitability associated with the progressive loss of CA1 pyramidal cells and the dispersion of dentate granule cells. Overall, our data identify SAVAs as an effective tool to eliminate GABAergic neurons from neuronal circuits underpinning high-order behaviors and cognition, and whose manipulation can recapitulate pathogenic cascades of epilepsy and other neuropsychiatric illnesses. PMID:22323713

  11. Neuroprotective Effect of Uncaria rhynchophylla in Kainic Acid-Induced Epileptic Seizures by Modulating Hippocampal Mossy Fiber Sprouting, Neuron Survival, Astrocyte Proliferation, and S100B Expression

    PubMed Central

    Liu, Chung-Hsiang; Lin, Yi-Wen; Tang, Nou-Ying; Liu, Hsu-Jan; Hsieh, Ching-Liang

    2012-01-01

    Uncaria rhynchophylla (UR), which is a traditional Chinese medicine, has anticonvulsive effect in our previous studies, and the cellular mechanisms behind this are still little known. Because of this, we wanted to determine the importance of the role of UR on kainic acid- (KA-) induced epilepsy. Oral UR for 6 weeks can successfully attenuate the onset of epileptic seizure in animal tests. Hippocampal mossy fiber sprouting dramatically decreased, while neuronal survival increased with UR treatment in hippocampal CA1 and CA3 areas. Furthermore, oral UR for 6 weeks significantly attenuated the overexpression of astrocyte proliferation and S100B proteins but not γ-aminobutyric acid A (GABAA) receptors. These results indicate that oral UR for 6 weeks can successfully attenuate mossy fiber sprouting, astrocyte proliferation, and S100B protein overexpression and increase neuronal survival in KA-induced epileptic rat hippocampus PMID:21837247

  12. Multicenter clinical assessment of improved wearable multimodal convulsive seizure detectors.

    PubMed

    Onorati, Francesco; Regalia, Giulia; Caborni, Chiara; Migliorini, Matteo; Bender, Daniel; Poh, Ming-Zher; Frazier, Cherise; Kovitch Thropp, Eliana; Mynatt, Elizabeth D; Bidwell, Jonathan; Mai, Roberto; LaFrance, W Curt; Blum, Andrew S; Friedman, Daniel; Loddenkemper, Tobias; Mohammadpour-Touserkani, Fatemeh; Reinsberger, Claus; Tognetti, Simone; Picard, Rosalind W

    2017-11-01

    New devices are needed for monitoring seizures, especially those associated with sudden unexpected death in epilepsy (SUDEP). They must be unobtrusive and automated, and provide false alarm rates (FARs) bearable in everyday life. This study quantifies the performance of new multimodal wrist-worn convulsive seizure detectors. Hand-annotated video-electroencephalographic seizure events were collected from 69 patients at six clinical sites. Three different wristbands were used to record electrodermal activity (EDA) and accelerometer (ACM) signals, obtaining 5,928 h of data, including 55 convulsive epileptic seizures (six focal tonic-clonic seizures and 49 focal to bilateral tonic-clonic seizures) from 22 patients. Recordings were analyzed offline to train and test two new machine learning classifiers and a published classifier based on EDA and ACM. Moreover, wristband data were analyzed to estimate seizure-motion duration and autonomic responses. The two novel classifiers consistently outperformed the previous detector. The most efficient (Classifier III) yielded sensitivity of 94.55%, and an FAR of 0.2 events/day. No nocturnal seizures were missed. Most patients had <1 false alarm every 4 days, with an FAR below their seizure frequency. When increasing the sensitivity to 100% (no missed seizures), the FAR is up to 13 times lower than with the previous detector. Furthermore, all detections occurred before the seizure ended, providing reasonable latency (median = 29.3 s, range = 14.8-151 s). Automatically estimated seizure durations were correlated with true durations, enabling reliable annotations. Finally, EDA measurements confirmed the presence of postictal autonomic dysfunction, exhibiting a significant rise in 73% of the convulsive seizures. The proposed multimodal wrist-worn convulsive seizure detectors provide seizure counts that are more accurate than previous automated detectors and typical patient self-reports, while maintaining a tolerable FAR for ambulatory

  13. Metabolic Therapy for Temporal Lobe Epilepsy in a Dish: Investigating Mechanisms of Ketogenic Diet using Electrophysiological Recordings in Hippocampal Slices

    PubMed Central

    Kawamura, Masahito Jr.; Ruskin, David N.; Masino, Susan A.

    2016-01-01

    The hippocampus is prone to epileptic seizures and is a key brain region and experimental platform for investigating mechanisms associated with the abnormal neuronal excitability that characterizes a seizure. Accordingly, the hippocampal slice is a common in vitro model to study treatments that may prevent or reduce seizure activity. The ketogenic diet is a metabolic therapy used to treat epilepsy in adults and children for nearly 100 years; it can reduce or eliminate even severe or refractory seizures. New insights into its underlying mechanisms have been revealed by diverse types of electrophysiological recordings in hippocampal slices. Here we review these reports and their relevant mechanistic findings. We acknowledge that a major difficulty in using hippocampal slices is the inability to reproduce precisely the in vivo condition of ketogenic diet feeding in any in vitro preparation, and progress has been made in this in vivo/in vitro transition. Thus far at least three different approaches are reported to reproduce relevant diet effects in the hippocampal slices: (1) direct application of ketone bodies; (2) mimicking the ketogenic diet condition during a whole-cell patch-clamp technique; and (3) reduced glucose incubation of hippocampal slices from ketogenic diet–fed animals. Significant results have been found with each of these methods and provide options for further study into short- and long-term mechanisms including Adenosine triphosphate (ATP)-sensitive potassium (KATP) channels, vesicular glutamate transporter (VGLUT), pannexin channels and adenosine receptors underlying ketogenic diet and other forms of metabolic therapy. PMID:27847463

  14. The new patient with a first seizure.

    PubMed

    King, Mark

    2003-04-01

    First seizures are common, with one in 20 people suffering a seizure at some time in their life. This article aims to outline the assessment of patients with a first seizure, including making an accurate diagnosis of both seizure type and an epilepsy syndrome, if present. Seizures are classified into generalised and partial (arising from a focal region in the brain) based on clinical and electroencephalogram findings. However, as a partial seizure may proceed to a tonic clonic phase, differentiation may be difficult. Inquiring directly about 'minor' epileptic symptoms before the episode such as absences, myoclonic jerks, visual or auditory hallucinations or feelings of déjà vu, is needed to attempt to make a epilepsy syndrome diagnosis, as this has practical implications for treatment, prognosis and genetic counselling. Generalised epilepsies should be treated initially with valproate, while partial epilepsies should be treated with carbamazepine and switched to newer agents if intolerance occurs.

  15. Ketone bodies do not directly alter excitatory or inhibitory hippocampal synaptic transmission.

    PubMed

    Thio, L L; Wong, M; Yamada, K A

    2000-01-25

    To determine the effect of the ketone bodies beta-hydroxybutyrate (betaHB) and acetoacetate (AA) on excitatory and inhibitory neurotransmission in the mammalian CNS. The ketogenic diet is presumed to be an effective anticonvulsant regimen for some children with medically intractable seizures. However, its mechanism of action remains a mystery. According to one hypothesis, ketone bodies have anticonvulsant properties. The authors examined the effect of betaHB and AA on excitatory and inhibitory synaptic transmission in rat hippocampal-entorhinal cortex slices and cultured hippocampal neurons. In cultured neurons, their effect was also directly assayed on postsynaptic receptor properties. Finally, their ability to prevent spontaneous seizures was determined in a hippocampal-entorhinal cortex slice model. betaHB and AA did not alter synaptic transmission in these models. The anticonvulsant properties of the ketogenic diet do not result from a direct effect of ketone bodies on the primary voltage and ligand gated ion channels mediating excitatory or inhibitory neurotransmission in the hippocampus.

  16. Comparison between Scalp EEG and Behind-the-Ear EEG for Development of a Wearable Seizure Detection System for Patients with Focal Epilepsy

    PubMed Central

    Gu, Ying; Cleeren, Evy; Dan, Jonathan; Claes, Kasper; Hunyadi, Borbála

    2017-01-01

    A wearable electroencephalogram (EEG) device for continuous monitoring of patients suffering from epilepsy would provide valuable information for the management of the disease. Currently no EEG setup is small and unobtrusive enough to be used in daily life. Recording behind the ear could prove to be a solution to a wearable EEG setup. This article examines the feasibility of recording epileptic EEG from behind the ear. It is achieved by comparison with scalp EEG recordings. Traditional scalp EEG and behind-the-ear EEG were simultaneously acquired from 12 patients with temporal, parietal, or occipital lobe epilepsy. Behind-the-ear EEG consisted of cross-head channels and unilateral channels. The analysis on Electrooculography (EOG) artifacts resulting from eye blinking showed that EOG artifacts were absent on cross-head channels and had significantly small amplitudes on unilateral channels. Temporal waveform and frequency content during seizures from behind-the-ear EEG visually resembled that from scalp EEG. Further, coherence analysis confirmed that behind-the-ear EEG acquired meaningful epileptic discharges similarly to scalp EEG. Moreover, automatic seizure detection based on support vector machine (SVM) showed that comparable seizure detection performance can be achieved using these two recordings. With scalp EEG, detection had a median sensitivity of 100% and a false detection rate of 1.14 per hour, while, with behind-the-ear EEG, it had a median sensitivity of 94.5% and a false detection rate of 0.52 per hour. These findings demonstrate the feasibility of detecting seizures from EEG recordings behind the ear for patients with focal epilepsy. PMID:29295522

  17. Usefulness of ketogenic diet in a girl with migrating partial seizures in infancy.

    PubMed

    Mori, Tatsuo; Imai, Katsumi; Oboshi, Taikan; Fujiwara, Yuh; Takeshita, Saoko; Saitsu, Hirotomo; Matsumoto, Naomichi; Takahashi, Yukitoshi; Inoue, Yushi

    2016-06-01

    Migrating partial seizures in infancy (MPSI) are an age-specific epilepsy syndrome characterized by migrating focal seizures, which are intractable to various antiepileptic drugs and cause severe developmental delay. We report a case of MPSI with heterozygous missense mutation in KCNT1, which was successfully managed by ketogenic diet. At age 2months, the patient developed epilepsy initially manifesting focal seizures with eye deviation and apnea, then evolving to secondarily generalized clonic convulsion. Various antiepileptic drugs including phenytoin, valproic acid, zonisamide, clobazam, levetiracetam, vitamin B6, and carbamazepine were not effective, but high-dose phenobarbital allowed discontinuation of midazolam infusion. Ictal scalp electroencephalogram showed migrating focal seizures. MPSI was suspected and she was transferred to our hospital for further treatment. Potassium bromide (KBr) was partially effective, but the effect was transient. High-dose KBr caused severe adverse effects such as over-sedation and hypercapnia, with no further effects on the seizures. At age 9months, we started a ketogenic diet, which improved seizure frequency and severity without obvious adverse effects, allowing her to be discharged from hospital. Ketogenic diet should be tried in patients with MPSI unresponsive to antiepileptic drugs. In MPSI, the difference in treatment response in patients with and those without KCNT1 mutation remains unknown. Accumulation of case reports would contribute to establish effective treatment options for MPSI. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  18. Picrotoxin-induced behavioral tolerance and altered susceptibility to seizures: effects of naloxone.

    PubMed

    Thomas, J; Nores, W L; Pariser, R

    1993-07-01

    The role of opiate mechanisms in the development of tolerance and altered susceptibility to seizures after repeated injections of picrotoxin was investigated. Independent groups of rats were pretreated with naloxone (0.3, 1.0, 3.0, and 10.0 mg/kg) or the saline vehicle and then tested for seizures induced by picrotoxin. The procedure was performed on 3 days at 1-week intervals, for a total of 3 testing days. Latencies to different types of seizures, the duration of postseizure immobility, and the number of focal seizure episodes were scored. In the vehicle-treated group, repeated picrotoxin injections led to an increased susceptibility to myoclonic and focal seizures and to decreased duration of postseizure immobility. Naloxone pretreatment significantly decreased the duration of the postseizure akinetic periods in the 1.0- and 10.0-mg/kg groups across all days, suggesting that endogenous opiates are involved in postseizure immobility and that there are interactions between opiate and picrotoxin mechanisms in some seizure-related behaviors. Naloxone did not alter the development of tolerance or sensitivity, indicating that naloxone-insensitive opiate mechanisms or nonopiate mechanisms may be involved in these processes.

  19. Theophylline-Induced Seizures: Clinical and Pathophysiologic Aspects

    PubMed Central

    Nakada, Tsutomu; Kwee, Ingrid L.; Lerner, Alfred M.; Remler, Michael P.

    1983-01-01

    The clinical features and management of theophylline-induced seizures are not well appreciated in spite of their unique aspects. These seizures tend to occur in neurologically intact patients and leave no or only minor neurologic sequelae if controlled early. They begin with focal motor seizures with or without secondary generalization and are followed by stupor or coma. They are responsive only to adjustment of theophylline dosage. Should the motor phenomenon persist, it takes the form of epilepsia partialis continua. Extensive workup for a structural brain lesion may be unrewarding. The electroencephalogram typically shows periodic lateralized epileptiform discharges, which may provide a diagnostic clue. PMID:6858124

  20. Neurobehavioral Deficits in a Rat Model of Recurrent Neonatal Seizures Are Prevented by a Ketogenic Diet and Correlate with Hippocampal Zinc/Lipid Transporter Signals.

    PubMed

    Tian, Tian; Ni, Hong; Sun, Bao-liang

    2015-10-01

    The ketogenic diet (KD) has been shown to be effective as an antiepileptic therapy in adults, but it has not been extensively tested for its efficacy in neonatal seizure-induced brain damage. We have previously shown altered expression of zinc/lipid metabolism-related genes in hippocampus following penicillin-induced developmental model of epilepsy. In this study, we further investigated the effect of KD on the neurobehavioral and cognitive deficits, as well as if KD has any influence in the activity of zinc/lipid transporters such as zinc transporter 3 (ZnT-3), MT-3, ApoE, ApoJ (clusterin), and ACAT-1 activities in neonatal rats submitted to flurothyl-induced recurrent seizures. Postnatal day 9 (P9), 48 Sprague-Dawley rats were randomly assigned to two groups: flurothyl-induced recurrent seizure group (EXP) and control group (CONT). On P28, they were further randomly divided into the seizure group without ketogenic diet (EXP1), seizure plus ketogenic diet (EXP2), the control group without ketogenic diet (CONT1), and the control plus ketogenic diet (CONT2). Neurological behavioral parameters of brain damage (plane righting reflex, cliff avoidance reflex, and open field test) were observed from P35 to P49. Morris water maze test was performed during P51-P57. Then hippocampal mossy fiber sprouting and the protein levels of ZnT3, MT3, ApoE, CLU, and ACAT-1 were detected by Timm staining and Western blot analysis, respectively. Flurothyl-induced neurobehavioral toxicology and aberrant mossy fiber sprouting were blocked by KD. In parallel with these behavioral changes, rats treated with KD (EXP2) showed a significant down-regulated expression of ZnT-3, MT-3, ApoE, clusterin, and ACAT-1 in hippocampus when compared with the non-KD-treated EXP1 group. Our findings provide support for zinc/lipid transporter signals being potential targets for the treatment of neonatal seizure-induced brain damage by KD.

  1. A tachykinin NK1 receptor antagonist, CP-122,721-1, attenuates kainic acid-induced seizure activity.

    PubMed

    Zachrisson, O; Lindefors, N; Brené, S

    1998-10-01

    Substance P (SP) can play an important role in neuronal survival. To analyze the role of SP in excitotoxicity, kainic acid (KA) was administered to rats and in situ hybridization was used to analyze the levels of the SP encoding preprotachykinin-A (PPT-A) mRNA in striatal and hippocampal subregions 1, 4, and 24 h and 7 days after KA. In striatum and piriform cortex, PPT-A mRNA peaked 4 h after KA while in hippocampus, levels peaked after 24 h. KA caused seizures and neuronal toxicity as indicated by a reduction of the number of neurons in the hippocampal CA1 subregion after 7 days. KA was later administered alone or following pretreatment with the tachykinin NK1 receptor antagonist CP-122,721-1 (0.3 mg/kg). The pretreatment decreased seizure activity and a negative correlation was found between seizure activity and survival of CA1 neurons. Conclusively, treatment with CP-122,721-1 has a seizure inhibiting property and may possibly counteract KA-induced nerve cell death in CA1. Copyright 1998 Elsevier Science B.V.

  2. Ictal electroencephalograms in neonatal seizures: characteristics and associations.

    PubMed

    Nagarajan, Lakshmi; Ghosh, Soumya; Palumbo, Linda

    2011-07-01

    The characteristics of ictal electroencephalograms in 160 neonatal seizures of 43 babies were correlated with mortality and neurodevelopmental outcomes. Neonatal seizures are focal at onset, most frequently temporal, and often occur during sleep. Twenty-one percent of babies with seizures died, and 76% of survivors manifested neurodevelopmental impairment during 2-6-year follow-up. A low-amplitude ictal electroencephalogram discharge was associated with increased mortality, and a frequency of <2 Hz with increased morbidity. Status epilepticus, ictal fractions, multiple foci, and bihemispheric involvement did not influence outcomes. Of 160 seizures, 99 exhibited no associated clinical features (electrographic seizures). Neonatal seizures with clinical correlates (electroclinical seizures) exhibited a higher amplitude and frequency of ictal electroencephalogram discharge than electrographic seizures. During electroclinical seizures, the ictal electroencephalogram was more likely to involve larger areas of the brain and to cross the midline. Mortality and morbidity were similar in babies with electroclinical and electrographic seizures, emphasizing the need to diagnose and treat both types. Ictal electroencephalogram topography has implications for electrode application during limited-channel, amplitude-integrated electroencephalograms. We recommend temporal and paracentral electrodes. Video electroencephalograms are important in diagnosing neonatal seizures and providing useful information regarding ictal electroencephalogram characteristics. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. The prevalence of thyrotoxicosis-related seizures.

    PubMed

    Song, Tae-Jin; Kim, Sun-Jung; Kim, Gyu Sik; Choi, Young-Chul; Kim, Won-Joo

    2010-09-01

    Central nervous system dysfunction, such as hyperexcitation, irritability, and disturbance of consciousness, may occur in patients with thyrotoxicosis. There are also a few case reports of seizures attributed to thyrotoxicosis. The objective of the present study was to determine the prevalence of seizures that appeared to be related to the thyrotoxic state in patients with thyrotoxicosis. We retrospectively determined the prevalence and clinical features of seizures in 3382 patients with hyperthyroidism. Among patients with seizures, we excluded those with other causes of seizures or a history of epilepsy. We did not exclude two patients in whom later work-up showed an abnormal magnetic resonance imaging, as their seizures resolved after they became euthyroid. Among the 3382 patients with hyperthyroidism, there were seven patients (0.2%) with seizures who met our criteria. Primary generalized tonic-clonic seizures occurred in four patients (57%), complex partial seizures with secondary generalized tonic-clonic seizures occurred in two patients (29%), and one patient had a focal seizure (14%). The initial electroencephalography (EEG) was normal in two patients (29%), had generalized slow activity in four patients (57%), and had diffuse generalized beta activity in one patient (14%). On magnetic resonance imaging, one patient had diffuse brain atrophy, and one had an old basal ganglia infarct. After the patients became euthyroid, the EEG was repeated and was normal in all patients. During follow-up periods ranging from 18 to 24 months, none of the patients had seizures. Hyperthyroidism is the precipitating cause of seizures in a small percentage of these patients. In these patients, the prognosis is good if they become euthyroid. The prevalence of thyrotoxicosis-related seizures reported here can be used in conjunction with the prevalence of thyrotoxicosis in the population to estimate the prevalence of thyrotoxicosis-related seizures in populations.

  4. Widespread changes in network activity allow non-invasive detection of mesial temporal lobe seizures.

    PubMed

    Lam, Alice D; Zepeda, Rodrigo; Cole, Andrew J; Cash, Sydney S

    2016-10-01

    Decades of experience with intracranial recordings in patients with epilepsy have demonstrated that seizures can occur in deep cortical regions such as the mesial temporal lobes without showing any obvious signs of seizure activity on scalp electroencephalogram. Predicated on the idea that these seizures are purely focal, currently, the only way to detect these 'scalp-negative seizures' is with intracranial recordings. However, intracranial recordings are only rarely performed in patients with epilepsy, and are almost never performed outside of the context of epilepsy. As such, little is known about scalp-negative seizures and their role in the natural history of epilepsy, their effect on cognitive function, and their association with other neurological diseases. Here, we developed a novel approach to non-invasively identify scalp-negative seizures arising from the mesial temporal lobe based on scalp electroencephalogram network connectivity measures. We identified 25 scalp-negative mesial temporal lobe seizures in 10 patients and obtained control records from an additional 13 patients, all of whom underwent recordings with foramen ovale electrodes and scalp electroencephalogram. Scalp data from these records were used to train a scalp-negative seizure detector, which consisted of a pair of logistic regression classifiers that used scalp electroencephalogram coherence properties as input features. On cross-validation performance, this detector correctly identified scalp-negative seizures in 40% of patients, and correctly identified the side of seizure onset for each seizure detected. In comparison, routine clinical interpretation of these scalp electroencephalograms failed to identify any of the scalp-negative seizures. Among the patients in whom the detector raised seizure alarms, 80% had scalp-negative mesial temporal lobe seizures. The detector had a false alarm rate of only 0.31 per day and a positive predictive value of 75%. Of the 13 control patients, false

  5. Effects of Edaravone on Hippocampal Antioxidants in EL Mice.

    PubMed

    Baba, Asami; Kawakami, Yasuhiko; Saito, Kenichi; Murashima, Yoshiya L; Itoh, Yasuhiko

    2016-01-01

    The role of oxidative stress in susceptibility to seizures has been the focus of several recent studies. The aim of the present study was to evaluate the antiepileptic effects of the free radical scavenger edaravone on EL mice, a strain that is highly susceptible to convulsive seizures. EL mice were treated intraperitoneally with edaravone or saline for 1 week. The levels of reduced glutathione (GSH), oxidized glutathione (GSSG) and 3 isozymes of superoxide dismutase (SOD) (cytoplasmic copper- and zinc-containing SOD, extracellular SOD, and mitochondrial manganese-containing SOD) were measured in the hippocampus, and electroencephalograms (EEGs) were used to evaluate seizure sensitivity. Hippocampal levels of GSSG were lower in the edaravone group than in the untreated control group, and the GSH/GSSG ratio, Cu/Zn-SOD, and EC-SOD activities were higher in the edaravone group. Edaravone shortened the duration of interictal spike discharges and clinically suppressed epileptic seizures. Edaravone increases antioxidant potency and reduces seizure susceptibility in EL mice, making it a promising novel antiepileptic agent.

  6. Incidence of seizures following initial ischemic stroke in a community-based cohort: The Framingham Heart Study.

    PubMed

    Stefanidou, Maria; Das, Rohit R; Beiser, Alexa S; Sundar, Banu; Kelly-Hayes, Margaret; Kase, Carlos S; Devinsky, Orrin; Seshadri, Sudha; Friedman, Daniel

    2017-04-01

    We examined the incidence of seizures following ischemic stroke in a community-based sample. All subjects with incident ischemic strokes in the Framingham Original and Offspring cohorts between 1982 and 2003 were identified and followed for up to 20 years to determine incidence of seizures. Seizure-type was based on the 2010 International League Against Epilepsy (ILAE) classification. Disability was stratified into mild/none, moderate and severe, based on post-stroke neurological deficit documentation according to the Framingham Heart Study (FHS) protocol and functional status was determined using the Barthel Index. An initial ischemic stroke occurred in 469 subjects in the cohort and seizures occurred in 25 (5.3%) of these subjects. Seizure incidence was similar in both large artery atherosclerosis (LAA) (6.8%) and cardio-embolic (CE) (6.2%) strokes. No seizures occurred following lacunar strokes. The predominant seizure type was focal seizure with or without evolution to bilateral convulsive seizure. One third of participants had seizures within the first 24h from stroke onset and half of all seizures occurred within the first 30days. On multivariate analysis, moderate and severe disability following stroke was associated with increased risk of incident seizure. Seizures occurred in approximately 5% of subjects after an ischemic stroke. One third of these seizures occurred in the first 24h after stroke and none followed lacunar strokes. Focal seizures with or without evolution in bilateral convulsive seizures were the most common seizure type. Moderate and severe disability was predictive of incident seizures. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  7. The patient had a normal magnetic resonance imaging and temporal lobe epilepsy secondary to a porencephalic cyst but showed structural lesions (hippocampal sclerosis)☆

    PubMed Central

    Matsubara, Teppei; Ayuzawa, Satoshi; Aoki, Tsukasa; Fujiomto, Ayataka; Osuka, Satoru; Matsumura, Akira

    2013-01-01

    Patients with a porencephalic cyst frequently develop intractable temporal lobe epilepsy (TLE). We report a surgically-treated male patient with intractable mesial TLE (mTLE) secondary to a porencephalic cyst. Although magnetic resonance imaging showed no hippocampal abnormalities, long-term video-electrocorticography revealed seizure onset discharges in the hippocampus. Temporal lobectomy brought an end to the patient's seizures. Hippocampal sclerosis was histopathologically confirmed (dual pathology). Careful evaluation of hippocampal epileptogenicity is required, and temporal lobectomy, which is less invasive than hemispherectomy, can be a treatment of choice for patients with mTLE secondary to a porencephalic cyst. PMID:25667851

  8. Early-life seizures alter synaptic calcium-permeable AMPA receptor function and plasticity

    PubMed Central

    Lippman-Bell, Jocelyn J.; Zhou, Chengwen; Sun, Hongyu; Feske, Joel S.; Jensen, Frances E.

    2016-01-01

    Calcium (Ca2+)-mediated1 signaling pathways are critical to synaptic plasticity. In adults, the NMDA glutamate receptor (NMDAR) represents a major route for activity-dependent synaptic Ca2+ entry. However, during neonatal development, when synaptic plasticity is high, many AMPA glutamate receptors (AMPARs) are also permeable to Ca2+ (CP-AMPAR) due to low GluA2 subunit expression, providing an additional route for activity- and glutamate-dependent Ca2+ influx and subsequent signaling. Therefore, altered hippocampal Ca2+ signaling may represent an age-specific pathogenic mechanism. We thus aimed to assess Ca2+ responses 48 hours after hypoxia-induced neonatal seizures (HS) in postnatal day (P)10 rats, a post-seizure time point at which we previously reported LTP attenuation. We found that Ca2+ responses were higher in brain slices from post-HS rats than in controls and this increase was CP-AMPAR-dependent. To determine whether synaptic CP-AMPAR expression was also altered post-HS, we assessed the expression of GluA2 at hippocampal synapses and the expression of long-term depression (LTD), which has been linked to the presence of synaptic GluA2. Here we report a decrease 48 hours after HS in synaptic GluA2 expression at synapses and LTD in hippocampal CA1. Given the potentially critical role of AMPAR trafficking in disease progression, we aimed to establish whether post-seizure in vivo AMPAR antagonist treatment prevented the enhanced Ca2+ responses, changes in GluA2 synaptic expression, and diminished LTD. We found that NBQX treatment prevents all three of these post-seizure consequences, further supporting a critical role for AMPARs as an age-specific therapeutic target. PMID:27521497

  9. Effects of hydroalcoholic extract of Coriandrum sativum on oxidative damage in pentylenetetrazole-induced seizures in rats

    PubMed Central

    Karami, Reza; Hosseini, Mahmoud; Mohammadpour, Toktam; Ghorbani, Ahmad; Sadeghnia, Hamid Reza; Rakhshandeh, Hassan; Vafaee, Farzaneh; Esmaeilizadeh, Mahdi

    2015-01-01

    Background: An important role for oxidative stress, as a consequence of epileptic seizures, has been suggested. Coriandrum sativum has been shown that have antioxidant effects. Central nervous system depressant effects of C. sativum have also been reported. In this study, the effects of hydroalcoholic extract of aerial parts of the plants on brain tissues oxidative damages following seizures induced by pentylenetetrazole (PTZ) was investigated in rats. Methods: The rats were divided into five groups and treated: (1) Control (saline), (2) PTZ (90 mg/kg, i.p.), (3-5) three doses (100, 500 and 1000 mg/kg of C. sativum extract (CSE) before PTZ. Latencies to the first minimal clonic seizures (MCS) and the first generalized tonic-clonic seizures (GTCS) were recorded. The cortical and hippocampal tissues were then removed for biochemical measurements. Results: The extract significantly increased the MCS and GTCS latencies (P < 0.01, P < 0.001) following PTZ-induced seizures. The malondialdehyde (MDA) levels in both cortical and hippocampal tissues of PTZ group were significantly higher than those of the control animals (P < 0.001). Pretreatment with the extract prevented elevation of the MDA levels (P < 0.010–P < 0.001). Following PTZ administration, a significant reduction in total thiol groups was observed in both cortical and hippocampal tissues (P < 0.050). Pre-treatment with the 500 mg/kg of the extract caused a significant prevention of decreased in total thiol concentration in the cortical tissues (P < 0.010). Conclusion: The present study showed that the hydroalcoholic extract of the aerial parts of C. sativum possess significant antioxidant and anticonvulsant activities. PMID:26056549

  10. Widespread changes in network activity allow non-invasive detection of mesial temporal lobe seizures

    PubMed Central

    Zepeda, Rodrigo; Cole, Andrew J.; Cash, Sydney S.

    2016-01-01

    Abstract Decades of experience with intracranial recordings in patients with epilepsy have demonstrated that seizures can occur in deep cortical regions such as the mesial temporal lobes without showing any obvious signs of seizure activity on scalp electroencephalogram. Predicated on the idea that these seizures are purely focal, currently, the only way to detect these ‘scalp-negative seizures’ is with intracranial recordings. However, intracranial recordings are only rarely performed in patients with epilepsy, and are almost never performed outside of the context of epilepsy. As such, little is known about scalp-negative seizures and their role in the natural history of epilepsy, their effect on cognitive function, and their association with other neurological diseases. Here, we developed a novel approach to non-invasively identify scalp-negative seizures arising from the mesial temporal lobe based on scalp electroencephalogram network connectivity measures. We identified 25 scalp-negative mesial temporal lobe seizures in 10 patients and obtained control records from an additional 13 patients, all of whom underwent recordings with foramen ovale electrodes and scalp electroencephalogram. Scalp data from these records were used to train a scalp-negative seizure detector, which consisted of a pair of logistic regression classifiers that used scalp electroencephalogram coherence properties as input features. On cross-validation performance, this detector correctly identified scalp-negative seizures in 40% of patients, and correctly identified the side of seizure onset for each seizure detected. In comparison, routine clinical interpretation of these scalp electroencephalograms failed to identify any of the scalp-negative seizures. Among the patients in whom the detector raised seizure alarms, 80% had scalp-negative mesial temporal lobe seizures. The detector had a false alarm rate of only 0.31 per day and a positive predictive value of 75%. Of the 13 control

  11. A common reference-based indirect comparison meta-analysis of eslicarbazepine versus lacosamide as add on treatments for focal epilepsy.

    PubMed

    Brigo, Francesco; Trinka, Eugen; Bragazzi, Nicola Luigi; Nardone, Raffaele; Milan, Alberto; Grillo, Elisabetta

    2016-11-01

    Eslicarbazepine acetate (ESL) and lacosamide (LCM) have recently emerged as add-on treatments in patients with focal epilepsy experiencing seizures despite adequate monotherapy. Both drugs enhance slow inactivation of voltage-gated sodium channels. To date no randomized controlled trial (RCT) has directly compared ESL with LCM as add-on treatments for focal epilepsy. Our aim was to indirectly compare the efficacy of ESL and LCM used as add-on treatments in patients with focal epilepsy using common reference-based indirect comparison meta-analysis. We systematically searched RCTs in which ESL or LCM has been used as add-on treatment in patients with focal epilepsy and compared with placebo. Following outcomes were considered: ≥50% reduction in seizure frequency; seizure freedom; treatment withdrawal for any reason; ≥25% increase in seizure frequency. Random-effects Mantel-Haenszel meta-analyses were performed to obtain odds ratios (ORs) for the efficacy of ESL or LCM versus placebo. Adjusted indirect comparisons were then made between ESL and LCM using the obtained results, and comparing the minimum and the highest effective recommended daily dose of each drug. Eight studies were included. Indirect comparisons adjusted for dose-effect showed no difference between ESL and LCM for responder rate, seizure freedom, and withdrawal rates. We could not assess increase in seizure frequency due to lack of data. Indirect comparisons failed to find a significant difference in efficacy between add-on ESL and LCM in patients with focal epilepsy. Direct head-to-head clinical trials comparing ESL with LCM as add-on antiepileptic treatment are required to confirm these results. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Automated detection of videotaped neonatal seizures of epileptic origin.

    PubMed

    Karayiannis, Nicolaos B; Xiong, Yaohua; Tao, Guozhi; Frost, James D; Wise, Merrill S; Hrachovy, Richard A; Mizrahi, Eli M

    2006-06-01

    This study aimed at the development of a seizure-detection system by training neural networks with quantitative motion information extracted from short video segments of neonatal seizures of the myoclonic and focal clonic types and random infant movements. The motion of the infants' body parts was quantified by temporal motion-strength signals extracted from video segments by motion-segmentation methods based on optical flow computation. The area of each frame occupied by the infants' moving body parts was segmented by clustering the motion parameters obtained by fitting an affine model to the pixel velocities. The motion of the infants' body parts also was quantified by temporal motion-trajectory signals extracted from video recordings by robust motion trackers based on block-motion models. These motion trackers were developed to adjust autonomously to illumination and contrast changes that may occur during the video-frame sequence. Video segments were represented by quantitative features obtained by analyzing motion-strength and motion-trajectory signals in both the time and frequency domains. Seizure recognition was performed by conventional feed-forward neural networks, quantum neural networks, and cosine radial basis function neural networks, which were trained to detect neonatal seizures of the myoclonic and focal clonic types and to distinguish them from random infant movements. The computational tools and procedures developed for automated seizure detection were evaluated on a set of 240 video segments of 54 patients exhibiting myoclonic seizures (80 segments), focal clonic seizures (80 segments), and random infant movements (80 segments). Regardless of the decision scheme used for interpreting the responses of the trained neural networks, all the neural network models exhibited sensitivity and specificity>90%. For one of the decision schemes proposed for interpreting the responses of the trained neural networks, the majority of the trained neural

  13. Ictal EEG/fMRI study of vertiginous seizures.

    PubMed

    Morano, Alessandra; Carnì, Marco; Casciato, Sara; Vaudano, Anna Elisabetta; Fattouch, Jinane; Fanella, Martina; Albini, Mariarita; Basili, Luca Manfredi; Lucignani, Giulia; Scapeccia, Marco; Tomassi, Regina; Di Castro, Elisabetta; Colonnese, Claudio; Giallonardo, Anna Teresa; Di Bonaventura, Carlo

    2017-03-01

    Vertigo and dizziness are extremely common complaints, related to either peripheral or central nervous system disorders. Among the latter, epilepsy has to be taken into consideration: indeed, vertigo may be part of the initial aura of a focal epileptic seizure in association with other signs/symptoms, or represent the only ictal manifestation, a rare phenomenon known as "vertiginous" or "vestibular" seizure. These ictal symptoms are usually related to a discharge arising from/involving temporal or parietal areas, which are supposed to be a crucial component of the so-called "vestibular cortex". In this paper, we describe three patients suffering from drug-resistant focal epilepsy, symptomatic of malformations of cortical development or perinatal hypoxic/ischemic lesions located in the posterior regions, who presented clusters of vertiginous seizures. The high recurrence rate of such events, recorded during video-EEG monitoring sessions, offered the opportunity to perform an ictal EEG/fMRI study to identify seizure-related hemodynamic changes. The ictal EEG/fMRI revealed the main activation clusters in the temporo-parieto-occipital regions, which are widely recognized to be involved in the processing of vestibular information. Interestingly, ictal deactivation was also detected in the ipsilateral cerebellar hemisphere, suggesting the ictal involvement of cortical-subcortical structures known to be part of the vestibular integration network. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Seizure-associated aphasia has good lateralizing but poor localizing significance.

    PubMed

    Loesch, Anna Mira; Steger, Hannah; Losher, Claudia; Hartl, Elisabeth; Rémi, Jan; Vollmar, Christian; Noachtar, Soheyl

    2017-09-01

    To investigate the occurrence of ictal and postictal aphasia in different focal epilepsy syndromes. We retrospectively analyzed the video-electroencephalographic monitoring data of 1,118 patients with focal epilepsy for seizure-associated aphasia (SAA). Statistical analysis included chi-square analysis and Fisher's exact test. We identified 102 of 1,118 patients (9.1%) in whom ictal or postictal aphasia (SAA) was part of their recorded seizures (n = 59 of 102; 57.8%) or who reported aphasia by history (n = 43; 42.2% only reported aphasia by history). Postictal aphasia was present in 18 patients (30.5%). Six of the 59 patients had both ictal and postictal aphasia (10.2%). SAA occurred either with left hemisphere seizure onset or with seizures spreading from the right to the left hemisphere. SAA was most common in patients with parieto-occipital epilepsy (10.9%; five of 46 patients), followed by patients with temporal (6.7%; 28 of 420 patients), focal (not further localized; 4.8%; 22 of 462 patients), and frontal epilepsy (2.1%; four of 190 patients; p = 0.04). SAA was more common in parieto-occipital epilepsy than in frontal epilepsy (p = 0.02). In contrast, there was no significant difference in SAA between temporal and parieto-occipital epilepsy (p = 0.36). SAA has a high lateralizing but limited localizing value, as it often reflects spread of epileptic activity into speech-harboring brain regions. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  15. Cerebrospinal fluid findings after epileptic seizures.

    PubMed

    Chatzikonstantinou, Anastasios; Ebert, Anne D; Hennerici, Michael G

    2015-12-01

    We aimed to evaluate ictally-induced CSF parameter changes after seizures in adult patients without acute inflammatory diseases or infectious diseases associated with the central nervous system. In total, 151 patients were included in the study. All patients were admitted to our department of neurology following acute seizures and received an extensive work-up including EEG, cerebral imaging, and CSF examinations. CSF protein elevation was found in most patients (92; 60.9%) and was significantly associated with older age, male sex, and generalized seizures. Abnormal CSF-to-serum glucose ratio was found in only nine patients (5.9%) and did not show any significant associations. CSF lactate was elevated in 34 patients (22.5%) and showed a significant association with focal seizures with impaired consciousness, status epilepticus, the presence of EEG abnormalities in general and epileptiform potentials in particular, as well as epileptogenic lesions on cerebral imaging. Our results indicate that non-inflammatory CSF elevation of protein and lactate after epileptic seizures is relatively common, in contrast to changes in CSF-to-serum glucose ratio, and further suggest that these changes are caused by ictal activity and are related to seizure type and intensity. We found no indication that these changes may have further-reaching pathological implications besides their postictal character.

  16. Microglial ablation and lipopolysaccharide preconditioning affects pilocarpine-induced seizures in mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mirrione, M.M.; Mirrione, M.M.; Konomosa, D.K.

    2010-04-01

    Activated microglia have been associated with neurodegeneration in patients and in animal models of Temporal Lobe Epilepsy (TLE), however their precise functions as neurotoxic or neuroprotective is a topic of significant investigation. To explore this, we examined the effects of pilocarpine-induced seizures in transgenic mice where microglia/macrophages were conditionally ablated. We found that unilateral ablation of microglia from the dorsal hippocampus did not alter acute seizure sensitivity. However, when this procedure was coupled with lipopolysaccharide (LPS) preconditioning (1 mg/kg given 24 h prior to acute seizure), we observed a significant pro-convulsant phenomenon. This effect was associated with lower metabolic activationmore » in the ipsilateral hippocampus during acute seizures, and could be attributed to activity in the mossy fiber pathway. These findings reveal that preconditioning with LPS 24 h prior to seizure induction may have a protective effect which is abolished by unilateral hippocampal microglia/macrophage ablation.« less

  17. Decreased number of interneurons and increased seizures in neuropilin 2 deficient mice: Implications for autism and epilepsy

    PubMed Central

    Gant, John C.; Thibault, Oliver; Blalock, Eric M.; Yang, Jun; Bachstetter, Adam; Kotick, James; Schauwecker, Paula E.; Hauser, Kurt F.; Smith, George M.; Mervis, Ron; Li, YanFang; Barnes, Gregory N.

    2010-01-01

    Summary Purpose Clinically, perturbations in the semaphorin signaling system have been associated with autism and epilepsy. The semaphorins have been implicated in guidance, migration, differentiation, and synaptic plasticity of neurons. The semaphorin 3F (Sema3F) ligand and its receptor, neuropilin 2 (NPN2) are highly expressed within limbic areas. NPN2 signaling may intimately direct the apposition of presynaptic and postsynaptic locations, facilitating the development and maturity of hippocampal synaptic function. To further understand the role of NPN2 signaling in central nevous system (CNS) plasticity, structural and functional alterations were assessed in NPN2 deficient mice. Methods In NPN2 deficient mice, we measured seizure susceptibility after kainic acid or pentylenetetrazol, neuronal excitability and synaptic throughput in slice preparations, principal and interneuron cell counts with immunocytochemical protocols, synaptosomal protein levels with immunoblots, and dendritic morphology with Golgi-staining. Results NPN2 deficient mice had shorter seizure latencies, increased vulnerability to seizure-related death, were more likely to develop spontaneous recurrent seizure activity after chemical challenge, and had an increased slope on input/output curves. Principal cell counts were unchanged, but GABA, parvalbumin, and neuropeptide Y interneuron cell counts were significantly reduced. Synaptosomal NPN2 protein levels and total number of GABAergic synapses were decreased in a gene dose-dependent fashion. CA1 pyramidal cells showed reduced dendritic length and complexity, as well as an increased number of dendritic spines. Discussion These data suggest the novel hypothesis that the Sema 3F signaling system's role in appropriate placement of subsets of hippocampal interneurons has critical downstream consequences for hippocampal function, resulting in a more seizure susceptible phenotype. PMID:18657176

  18. The phenotype of bilateral hippocampal sclerosis and its management in "real life" clinical settings.

    PubMed

    Sen, Arjune; Dugan, Patricia; Perucca, Piero; Costello, Daniel; Choi, Hyunmi; Bazil, Carl; Radtke, Rod; Andrade, Danielle; Depondt, Chantal; Heavin, Sinead; Adcock, Jane; Pickrell, W Owen; McGinty, Ronan; Nascimento, Fábio; Smith, Philip; Rees, Mark I; Kwan, Patrick; O'Brien, Terence J; Goldstein, David; Delanty, Norman

    2018-06-14

    There is little detailed phenotypic characterization of bilateral hippocampal sclerosis (HS). We therefore conducted a multicenter review of people with pharmacoresistant epilepsy and bilateral HS to better determine their clinical characteristics. Databases from 11 EPIGEN centers were searched. For identified cases, clinicians reviewed the medical notes, imaging, and electroencephalographic (EEG), video-EEG, and neuropsychometric data. Data were irretrievably anonymized, and a single database was populated to capture all phenotypic information. These data were compared with phenotyped cases of unilateral HS from the same centers. In total, 96 patients with pharmacoresistant epilepsy and bilateral HS were identified (43 female, 53 male; age range = 8-80 years). Twenty-five percent had experienced febrile convulsions, and 27% of patients had experienced status epilepticus. The mean number of previously tried antiepileptic drugs was 5.32, and the average number of currently prescribed medications was 2.99; 44.8% of patients had cognitive difficulties, and 47.9% had psychiatric comorbidity; 35.4% (34/96) of patients continued with long-term medical therapy alone, another 4 being seizure-free on medication. Sixteen patients proceeded to, or were awaiting, neurostimulation, and 11 underwent surgical resection. One patient was rendered seizure-free postresection, with an improvement in seizures for 3 other cases. By comparison, of 201 patients with unilateral HS, a significantly higher number (44.3%) had febrile convulsions and only 11.4% had experienced status epilepticus. Importantly, 41.8% (84/201) of patients with unilateral HS had focal aware seizures, whereas such seizures were less frequently observed in people with bilateral HS, and were never observed exclusively (P = .002; Fisher's exact test). The current work describes the phenotypic spectrum of people with pharmacoresistant epilepsy and bilateral HS, highlights salient clinical differences from patients

  19. Bumetanide enhances phenobarbital efficacy in a rat model of hypoxic neonatal seizures.

    PubMed

    Cleary, Ryan T; Sun, Hongyu; Huynh, Thanhthao; Manning, Simon M; Li, Yijun; Rotenberg, Alexander; Talos, Delia M; Kahle, Kristopher T; Jackson, Michele; Rakhade, Sanjay N; Berry, Gerard T; Berry, Gerard; Jensen, Frances E

    2013-01-01

    Neonatal seizures can be refractory to conventional anticonvulsants, and this may in part be due to a developmental increase in expression of the neuronal Na(+)-K(+)-2 Cl(-) cotransporter, NKCC1, and consequent paradoxical excitatory actions of GABAA receptors in the perinatal period. The most common cause of neonatal seizures is hypoxic encephalopathy, and here we show in an established model of neonatal hypoxia-induced seizures that the NKCC1 inhibitor, bumetanide, in combination with phenobarbital is significantly more effective than phenobarbital alone. A sensitive mass spectrometry assay revealed that bumetanide concentrations in serum and brain were dose-dependent, and the expression of NKCC1 protein transiently increased in cortex and hippocampus after hypoxic seizures. Importantly, the low doses of phenobarbital and bumetanide used in the study did not increase constitutive apoptosis, alone or in combination. Perforated patch clamp recordings from ex vivo hippocampal slices removed following seizures revealed that phenobarbital and bumetanide largely reversed seizure-induced changes in EGABA. Taken together, these data provide preclinical support for clinical trials of bumetanide in human neonates at risk for hypoxic encephalopathy and seizures.

  20. Efficacy and safety of lacosamide in infants and young children with refractory focal epilepsy.

    PubMed

    Grosso, Salvatore; Parisi, Pasquale; Spalice, Alberto; Verrotti, Alberto; Balestri, Paolo

    2014-01-01

    Lacosamide is effective and well-tolerated antiepileptic drug (AED) in both children and adults. This multicentric, prospective study investigates the efficacy and safety of lacosamide adjunctive therapy in children aged less than four years presenting with refractory focal seizures. Lacosamide was added to the baseline therapy at a starting dose of 1-2 mg/kg/day and titrated to the final dose, ranging from 7 to 15.5 mg/kg/day. Efficacy was evaluated after a three-month period of therapy. When possible, we compared the initial efficacy and the retention after a minimum of 12 months of lacosamide, with regard to loss of efficacy (defined as the return to the baseline seizure frequency). Twenty-four children were enrolled in the study. Mean age was 2.7 years. After a minimum three-month period of lacosamide add-on therapy, ten (42%) patients were responders (more than a 50% decrease in seizure frequency), of whom 4 (17%) became seizure free. Retention rate, after a minimum of 12 months of lacosamide, was evaluated in a group of 18 patients. In the latter group, eight patients (44%) were initial responders (three of whom seizure free). After 12 months of follow-up, four of them (22%) maintained the improvement, 2 (11%) of whom remained seizure free. A loss of efficacy was observed in 4 of the initial responders (50%). Adverse events were seen in 8 (33%) patients. We conclude that lacosamide is an effective and a well-tolerated antiepileptic drug in an etiologically wide range of focal seizures. Therefore, lacosamide might represent a possible therapeutic option in infants and young children affected by uncontrolled focal epilepsy. Copyright © 2013 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  1. Surgical Management and Long-Term Seizure Outcome After Surgery for Temporal Lobe Epilepsy Associated with Cerebral Cavernous Malformations.

    PubMed

    Yang, Peng-Fan; Pei, Jia-Sheng; Jia, Yan-Zeng; Lin, Qiao; Xiao, Hui; Zhang, Ting-Ting; Zhong, Zhong-Hui

    2018-02-01

    Operative strategies for cerebral cavernous malformation (CCM)-associated temporal lobe epilepsy and timing of surgical intervention continue to be debated. This study aimed to establish an algorithm to evaluate the efficacy of surgical intervention strategies, to maximize positive surgical outcomes and minimize postsurgical neurologic deficits. 47 patients having undergone operation for CCM-associated temporal lobe epilepsy were retrospectively reviewed. They had received a diagnostic series for seizure localization, including long-term video electroencephalography (vEEG), high-resolution magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET-CT). In patients with mesial temporal lobe CCMs, the involved structures (amygdala, hippocampus, or parahippocampal gyrus) were resected in addition to the lesions. Patients with neocortical epileptogenic CCM underwent extended lesionectomy guided by intraoperative electrocorticography; further performance of amygdalohippocampectomy depended on the extent of hippocampal epileptogenicity. The study cohort contained 28 patients with drug-resistant epilepsy (DRE), 12 with chronic epilepsy (CE), and 7 with sporadic seizure (SS). Normal temporal lobe metabolism was seen in 7/7 patients of the SS group. Hypometabolism was found in all patients with chronic disease except for those with posterior inferior and middle temporal gyrus cavernous malformations (CMs). Of the 31 patients with superficial neocortical CCM, 7 had normal PET without hippocampal sclerosis, 14 had ipsilateral temporal lobe hypometabolism without hippocampal sclerosis, and 10 had obvious hippocampal sclerosis and hypometabolism. Seizure freedom in DRE, CE, and SS was 82.1%, 75%, and 100%, respectively. A significant difference was found between lesion laterality and postoperative seizure control; the rate was lower in left-sided cases because of less aggressive resection. Our study demonstrates that the data from the

  2. Subacute and chronic electrical stimulation of the hippocampus on intractable temporal lobe seizures: preliminary report.

    PubMed

    Velasco, A L; Velasco, M; Velasco, F; Menes, D; Gordon, F; Rocha, L; Briones, M; Márquez, I

    2000-01-01

    Recent animal experiments show that the application of an electrical stimulus to the amygdala or hippocampus following the kindling stimulus produced a significant and long-lasting suppressive effect on this experimental model of epilepsy. This is a preliminary report on the development of a surgical neuromodulatory procedure by chronic electrical stimulation of the hippocampus (CHCS) for control of intractable temporal lobe seizures in patients in whom anterior temporal lobectomy is not advisable, i.e., patients with bilateral temporal foci or a unilateral focus spreading to surrounding cerebral regions of the dominant hemisphere. This work was divided in two main consecutive stages. In the first stage, we demonstrated that subacute hippocampal stimulation (SAHCS) blocks intractable temporal lobe epileptogenesis with no additional damage to the stimulated tissue, and in a second stage, we attempt to demonstrate that CHCS may produce a sustained, long-lasting antiepileptic condition without additional undesirable effects on language and memory. In addition, taking advantage of this unique and ethically permissible situation, we attempt to determine whether or not the antiepileptic effects of SAHCS and CHCS are due to inhibition of the stimulation of hippocampal tissue by means of a number of electrophysiological, single photon computed tomography (SPECT) perfusion, and autoradiographic techniques.SAHCS during 3-4 weeks prior to anterior temporal lobectomy applied to a critical area located either at the anterior Pes hippocampus close to the amygdala or at the parahippocampal gyrus close to the entorhinal cortex abolished clinical seizures and significantly decreased the number of interictal spikes at focus after 5-6 days. Microscopy analysis of the stimulated tissue showed no evident histopathological differences between stimulated vs. non-stimulated hippocampal tissues. Additionally, CHCS persistently blocked temporal lobe epileptogenesis for 3-4 months with no

  3. Losigamone add-on therapy for focal epilepsy.

    PubMed

    Xiao, Yousheng; Luo, Man; Wang, Jin; Luo, Hongye

    2018-01-22

    Epilepsy is a common neurologic disorder, affecting approximately 50 million people worldwide; nearly a third of these people have epilepsy that is not well controlled by a single antiepileptic drug (AED) and they usually require treatment with a combination of two or more AEDs. In recent years, many newer AEDs have been investigated as add-on therapy for focal epilepsy; losigamone is one of these drugs and is the focus of this systematic review. This is an update of a Cochrane review first published in 2012 (Cochrane Database of Systematic Reviews 2012, Issue 6) and updated in 2015. To investigate the efficacy and safety of losigamone when used as an add-on therapy for focal epilepsy. For the latest update on 9 February 2017, we searched the Cochrane Epilepsy Specialized Register, CENTRAL and MEDLINE . We searched trials registers and contacted the manufacturer of losigamone and authors of included studies for additional information. We did not impose any language restrictions. Randomized controlled, add-on trials comparing losigamone with placebo for focal epilepsy. Two review authors independently assessed trial quality and extracted data. The primary outcomes were 50% or greater reduction in seizure frequency and seizure freedom; the secondary outcomes were treatment withdrawal and adverse events. Results are presented as risk ratios (RRs) with 95% confidence intervals (CIs) or 99% CIs (for the individual listed adverse events to make an allowance for multiple testing). Two trials involving a total of 467 participants, aged over 18 years, were eligible for inclusion. Both trials assessed losigamone 1200 mg/day or 1500 mg/day as an add-on therapy for focal epilepsy. We assessed one trial as being of good methodological quality while the other was of uncertain quality. For the efficacy outcomes, results did show that participants taking losigamone were significantly more likely to achieve a 50% or greater reduction in seizure frequency (RR 1.76, 95% CI 1.14 to 2

  4. Empathy in Hippocampal Amnesia

    PubMed Central

    Beadle, J. N.; Tranel, D.; Cohen, N. J.; Duff, M. C.

    2013-01-01

    Empathy is critical to the quality of our relationships with others and plays an important role in life satisfaction and well-being. The scientific investigation of empathy has focused on characterizing its cognitive and neural substrates, and has pointed to the importance of a network of brain regions involved in emotional experience and perspective taking (e.g., ventromedial prefrontal cortex, amygdala, anterior insula, cingulate). While the hippocampus has rarely been the focus of empathy research, the hallmark properties of the hippocampal declarative memory system (e.g., representational flexibility, relational binding, on-line processing capacity) make it well-suited to meet some of the crucial demands of empathy, and a careful investigation of this possibility could make a significant contribution to the neuroscientific understanding of empathy. The present study is a preliminary investigation of the role of the hippocampal declarative memory system in empathy. Participants were three patients (1 female) with focal, bilateral hippocampal (HC) damage and severe declarative memory impairments and three healthy demographically matched comparison participants. Empathy was measured as a trait through a battery of gold standard questionnaires and through on-line ratings and prosocial behavior in response to a series of empathy inductions. Patients with hippocampal amnesia reported lower cognitive and emotional trait empathy than healthy comparison participants. Unlike healthy comparison participants, in response to the empathy inductions hippocampal patients reported no increase in empathy ratings or prosocial behavior. The results provide preliminary evidence for a role for hippocampal declarative memory in empathy. PMID:23526601

  5. The piriform, perirhinal, and entorhinal cortex in seizure generation

    PubMed Central

    Vismer, Marta S.; Forcelli, Patrick A.; Skopin, Mark D.; Gale, Karen; Koubeissi, Mohamad Z.

    2015-01-01

    Understanding neural network behavior is essential to shed light on epileptogenesis and seizure propagation. The interconnectivity and plasticity of mammalian limbic and neocortical brain regions provide the substrate for the hypersynchrony and hyperexcitability associated with seizure activity. Recurrent unprovoked seizures are the hallmark of epilepsy, and limbic epilepsy is the most common type of medically-intractable focal epilepsy in adolescents and adults that necessitates surgical evaluation. In this review, we describe the role and relationships among the piriform (PIRC), perirhinal (PRC), and entorhinal cortex (ERC) in seizure-generation and epilepsy. The inherent function, anatomy, and histological composition of these cortical regions are discussed. In addition, the neurotransmitters, intrinsic and extrinsic connections, and the interaction of these regions are described. Furthermore, we provide evidence based on clinical research and animal models that suggest that these cortical regions may act as key seizure-trigger zones and, even, epileptogenesis. PMID:26074779

  6. Localization of cortical tissue optical changes during seizure activity in vivo with optical coherence tomography

    PubMed Central

    Eberle, Melissa M.; Hsu, Mike S.; Rodriguez, Carissa L.; Szu, Jenny I.; Oliveira, Michael C.; Binder, Devin K.; Park, B. Hyle

    2015-01-01

    Optical coherence tomography (OCT) is a high resolution, minimally invasive imaging technique, which can produce depth-resolved cross-sectional images. In this study, OCT was used to detect changes in the optical properties of cortical tissue in vivo in mice during the induction of global (pentylenetetrazol) and focal (4-aminopyridine) seizures. Through the use of a confidence interval statistical method on depth-resolved volumes of attenuation coefficient, we demonstrated localization of regions exhibiting both significant positive and negative changes in attenuation coefficient, as well as differentiating between global and focal seizure propagation. PMID:26137382

  7. Activation of either the ETA or the ETB receptors is involved in the development of electrographic seizures following intrahippocampal infusion of the endothelin-1 in immature rats.

    PubMed

    Tsenov, Grygoriy; Vondrakova, Katerina; Otahal, Jakub; Burchfiel, James; Kubova, Hana

    2015-03-01

    The period around birth is a risky time for stroke in infants, which is associated with two major acute and subacute processes: anatomical damage and seizures. It is unclear as to what extent each of these processes independently contributes to poor outcome. Furthermore, it is unclear whether there is an interaction between the two processes - does seizure activity cause additional brain damage beyond that produced by ischemia and/or does brain damage foster seizures? The model of focal cerebral ischemia induced by the intrahippocampal infusion of endothelin-1 (ET-1) in 12-day-old rat was used to examine the role of the endothelin receptors in the development of focal ischemia, symptomatic acute seizures and neurodegeneration. ET-1 (40pmol/μl) was infused either alone or co-administered with selective antagonists of ETA (BQ123; 70nmol/μl) or ETB receptors (BQ788; 70nmol/1μl). Effects of activation of ETB receptors were studied using selective agonist 4-Ala-ET-1 (40pmol/1μl). Regional cerebral blood flow (rCBF) and tissue oxygenation (pO2) were measured in anesthetized animals with a Doppler-flowmeter and a pO2-sensor, respectively. Seizure development was assessed with video-EEG in freely moving rats. Controls received the corresponding volume of the appropriate vehicle (10mM PBS or 0.01% DMSO-PBS solution; pH7.4). The extent of hippocampal lesion was determined using FluoroJade B staining performed 24h after ET-1 infusion. Infusion of ET-1 or ET-1+ETB receptor antagonist reduced rCBF to ~25% and pO2 to ~10% for about 1.5h, whereas selective ETB agonist, ET-1+ETA antagonist and the PBS vehicle had only negligible effect on the rCBF and pO2 levels. Reduction of rCBF was associated with the development of lesion in the injected hippocampus. In all groups, except sham operated and PBS controls, epileptiform activity was observed after activation of the ETA or the ETB receptors. The data revealed a positive correlation between the severity of morphological damage

  8. Altered synchrony and loss of consciousness during frontal lobe seizures.

    PubMed

    Bonini, Francesca; Lambert, Isabelle; Wendling, Fabrice; McGonigal, Aileen; Bartolomei, Fabrice

    2016-02-01

    Loss of consciousness (LOC) in frontal lobe epilepsy (FLE) has been rarely specifically studied until now. In this study we evaluated the LOC in a population of patients with FLE and studied the relationship between changes in synchrony and degree of LOC. 24 patients undergoing stereoelectroencephalography (SEEG) during pre-surgical evaluation of FLE were studied. The LOC intensity was scored using the Consciousness Seizure Scale (CSS). For each studied seizure (n=52), interdependencies between signals recorded from 5 brain regions were estimated as a function of time by using non-linear regression analysis (h(2) coefficient). Seizures were divided into 3 groups according to the CSS scale: group A (no LOC) with a score ⩽2, group B (intermediate or partial LOC) with a score ranging from 3 to 5, and group C (maximal LOC) with a score ⩾6. The majority of seizures in FLE patients disclosed significant LOC, particularly for patients with prefrontal lobe seizures. Mean correlation values were significantly different between groups A and C (p<0.001), the maximal values of synchrony being observed in group C. Differences were significant for interaction affecting the external prefrontal cortex (p=0.004) (p=0.01) and the parietal cortex. In addition, a significant correlation was found between CSS scores and correlations values (h(2)) of the prefrontal and the parietal region but not with the premotor cortex. This study indicates that in FLE, prefrontal seizures frequently alter consciousness. As in other focal seizures, LOC appears to be related to changes in synchrony in prefrontal and parietal associative cortices. LOC in FLE is frequent and as in other focal epilepsies is related to an alteration of prefrontal-parietal network. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  9. CXCR4 antagonist AMD3100 reverses the neurogenesis promoted by enriched environment and suppresses long-term seizure activity in adult rats of temporal lobe epilepsy.

    PubMed

    Zhou, Zhike; Liu, Tingting; Sun, Xiaoyu; Mu, Xiaopeng; Zhu, Gang; Xiao, Ting; Zhao, Mei; Zhao, Chuansheng

    2017-03-30

    It has been showed that enriched environment (EE) enhances the hippocampal neurogenesis and improves the cognitive impairments, accompanied by the increased expressions of stromal cell-derived factor-1 (SDF-1) in adult rats of temporal lobe epilepsy (TLE). We examined whether the enhanced neurogenesis and improved cognitive functions induced by EE following seizures were mediated by SDF-1/CXCR4 pathway. Therefore, we investigated the effects of the EE combined with CXCR4 antagonist AMD3100 on neurogenesis, cognitive functions and the long-term seizure activity in the TLE model. Adult rats were randomly assigned as control rats, rats treated with EE, rats subjected to status epilepticus (SE), post-SE rats treated with EE, AMD3100 or EE combined with AMD3100 respectively. We used immunofluorescence staining to analyze the hippocampal neurogenesis and Nissl staining to evaluate hippocampal damage. Electroencephalography was used to measure the frequency and mean duration of spontaneous seizures. Cognitive function was evaluated by Morris water maze test. EE treatment significantly, as well as improved cognitive impairments and decreased long-term seizure activity, and that these effects might be mediated through SDF-1/CXCR4 pathway during the chronic stage of TLE. Although AMD3100 reversed the effect of EE on neurogenesis, it did not abolish the cognitive improvement induced by EE following seizures. More importantly, EE combined with AMD3100 treatment significantly suppressed long-term seizure activity, which provided promising evidences to treat TLE. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Earlier tachycardia onset in right than left mesial temporal lobe seizures.

    PubMed

    Kato, Kazuhiro; Jin, Kazutaka; Itabashi, Hisashi; Iwasaki, Masaki; Kakisaka, Yosuke; Aoki, Masashi; Nakasato, Nobukazu

    2014-10-07

    To clarify whether the presence and timing of peri-ictal heart rate (HR) change is a seizure lateralizing sign in patients with mesial temporal lobe epilepsy (mTLE). Long-term video EEGs were retrospectively reviewed in 21 patients, 7 men and 14 women aged 13 to 67 years, diagnosed as mTLE with MRI lesions in the mesial temporal structures (hippocampal sclerosis in 20 cases, amygdala hypertrophy in 1 case). Seventy-seven partial seizures without secondary generalization were extracted. Peri-ictal HR change was compared between 29 right seizures (9 patients) and 48 left seizures (12 patients). HR abruptly increased in all 29 right seizures and 42 of 48 left seizures. Onset time of HR increase in relation to ictal EEG onset was significantly earlier in right seizures than in left seizures (mean ± SD, -11.5 ± 14.8 vs 9.2 ± 21.7 seconds; p < 0.0001). Time of maximum HR was also significantly earlier in right seizures than in left seizures (36.0 ± 18.1 vs 58.0 ± 28.7 seconds; p < 0.0001). Maximum HR changes from baseline showed no significant difference between right and left seizures (47.5 ± 19.1 vs 40.8 ± 20.0/min). Significantly earlier tachycardia in right than left mTLE seizures supports previous hypotheses that the right cerebral hemisphere is dominant in the sympathetic network. No HR change, or delayed tachycardia possibly due to seizure propagation to the right hemisphere, may be a useful lateralizing sign of left mTLE seizures. © 2014 American Academy of Neurology.

  11. Stiripentol add-on therapy for focal refractory epilepsy.

    PubMed

    Brigo, Francesco; Igwe, Stanley C; Bragazzi, Nicola Luigi

    2018-05-10

    This is an updated version of the Cochrane review last published in 2015 (Issue 10). For nearly 30% of people with epilepsy, seizures are not controlled by current treatments. Stiripentol is a new antiepileptic drug (AED) that was developed in France and was approved by the European Medicines Agency (EMA) in 2007 for the treatment of Dravet syndrome as an adjunctive therapy with valproate and clobazam, with promising effects. To evaluate the efficacy and tolerability of stiripentol as add-on treatment for people with focal refractory epilepsy who are taking AEDs. For the latest update, we searched the following databases on 21 August 2017: Cochrane Epilepsy Specialized Register, CENTRAL , MEDLINE, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP). We contacted Biocodex (the manufacturer of stiripentol) and epilepsy experts to identify published, unpublished and ongoing trials. Randomised, controlled, add-on trials of stiripentol in people with focal refractory epilepsy. Review authors independently selected trials for inclusion and extracted data. Outcomes investigated included 50% or greater reduction in seizure frequency, seizure freedom, adverse effects, treatment withdrawal and changes in quality of life. On the basis of our selection criteria, we included no new studies in the present review. Only one study was included from the earlier review (32 children with focal epilepsy). This study adopted a 'responder enriched' design and found no clear evidence of a reduction in seizure frequency (≥ 50% seizure reduction) (risk ratio (RR) 1.51, 95% confidence interval (CI) 0.81 to 2.82, low-quality evidence) nor evidence of seizure freedom (RR 1.18, 95% CI 0.31 to 4.43, low-quality evidence) when add-on stiripentol was compared with placebo. Stiripentol led to a greater risk of adverse effects considered as a whole (RR 2.65, 95% CI 1.08 to 6.47, low-quality evidence). When specific adverse events were considered, confidence

  12. AED discontinuation may be dangerous for seizure-free patients.

    PubMed

    Schmidt, Dieter

    2011-02-01

    Despite its benefits, stopping antiepileptic drugs (AEDs) in seizure-free patients is associated with several risks. AED discontinuation doubles the risk of seizure recurrence for up to 2 years compared with continued treatment. On average, one in three patients has a seizure recurrence, though the range can go up to 66% (34%, range 12-66%, 95% CI: 27-43). Furthermore, the outcome of treating a seizure recurrence in patients who have been seizure-free for years is surprisingly poor in some patients. Although the long-term prognosis is not worsened by drug discontinuation, one in five patients does not re-enter remission and for some patients, it may take several years to become seizure-free again. The risk of seizure recurrence is particularly high for those with juvenile myoclonic epilepsy and symptomatic focal epilepsy, the most frequent epilepsies in adults. Seizure-recurrence may have devastating, medical, psychological and social consequences for the individual, for example injury, loss of self-esteem, unemployment and losing a driver's license. Discontinuation should be avoided in patients with a high risk of seizure recurrence. Given these risks, patients will ultimately have to decide themselves whether they wish to discontinue drug treatment after full informed consent.

  13. Autonomic headache with autonomic seizures: a case report.

    PubMed

    Ozge, Aynur; Kaleagasi, Hakan; Yalçin Tasmertek, Fazilet

    2006-10-01

    The aim of the report is to present a case of an autonomic headache associated with autonomic seizures. A 19-year-old male who had had complex partial seizures for 15 years was admitted with autonomic complaints and left hemicranial headache, independent from seizures, that he had had for 2 years and were provoked by watching television. Brain magnetic resonance imaging showed right hippocampal sclerosis and electroencephalography revealed epileptic activity in right hemispheric areas. Treatment with valproic acid decreased the complaints. The headache did not fulfil the criteria for the diagnosis of trigeminal autonomic cephalalgias, and was different from epileptic headache, which was defined as a pressing type pain felt over the forehead for several minutes to a few hours. Although epileptic headache responds to anti-epileptics and the complaints of the present case decreased with antiepileptics, it has been suggested that the headache could be a non-trigeminal autonomic headache instead of an epileptic headache.

  14. SCN3A deficiency associated with increased seizure susceptibility

    PubMed Central

    Lamar, Tyra; Vanoye, Carlos G.; Calhoun, Jeffrey; Wong, Jennifer C.; Dutton, Stacey B.B.; Jorge, Benjamin S.; Velinov, Milen; Escayg, Andrew; Kearney, Jennifer A.

    2017-01-01

    Mutations in voltage-gated sodium channels expressed highly in the brain (SCN1A, SCN2A, SCN3A, and SCN8A) are responsible for an increasing number of epilepsy syndromes. In particular, mutations in the SCN3A gene, encoding the pore-forming Nav1.3 α subunit, have been identified in patients with focal epilepsy. Biophysical characterization of epilepsy-associated SCN3A variants suggests that both gain- and loss-of-function SCN3A mutations may lead to increased seizure susceptibility. In this report, we identified a novel SCN3A variant (L247P) by whole exome sequencing of a child with focal epilepsy, developmental delay, and autonomic nervous system dysfunction. Voltage clamp analysis showed no detectable sodium current in a heterologous expression system expressing the SCN3A-L247P variant. Furthermore, cell surface biotinylation demonstrated a reduction in the amount of SCN3A-L247P at the cell surface, suggesting the SCN3A-L247P variant is a trafficking-deficient mutant. To further explore the possible clinical consequences of reduced SCN3A activity, we investigated the effect of a hypomorphic Scn3a allele (Scn3aHyp) on seizure susceptibility and behavior using a gene trap mouse line. Heterozygous Scn3a mutant mice (Scn3a+/Hyp) did not exhibit spontaneous seizures nor were they susceptible to hyperthermia-induced seizures. However, they displayed increased susceptibility to electroconvulsive (6 Hz) and chemiconvulsive (flurothyl and kainic acid) induced seizures. Scn3a+/Hyp mice also exhibited deficits in locomotor activity and motor learning. Taken together, these results provide evidence that loss-of-function of SCN3A caused by reduced protein expression or deficient trafficking to the plasma membrane may contribute to increased seizure susceptibility. PMID:28235671

  15. Temporal pole abnormalities detected by 3 T MRI in temporal lobe epilepsy due to hippocampal sclerosis: No influence on seizure outcome after surgery.

    PubMed

    Casciato, Sara; Picardi, Angelo; D'Aniello, Alfredo; De Risi, Marco; Grillea, Giovanni; Quarato, Pier Paolo; Mascia, Addolorata; Grammaldo, Liliana G; Meldolesi, Giulio Nicolo'; Morace, Roberta; Esposito, Vincenzo; Di Gennaro, Giancarlo

    2017-05-01

    To assess the clinical significance of temporal pole abnormalities (temporopolar blurring, TB, and temporopolar atrophy, TA) detected by using 3 Tesla MRI in the preoperative workup in patients with temporal lobe epilepsy due to hippocampal sclerosis (TLE-HS) who underwent surgery. We studied 78 consecutive patients with TLE-HS who underwent surgery and were followed up for at least 2 years. Based on findings of pre-surgical 3 Tesla MRI, patients were subdivided in subgroups according to the presence of TB or TA. Subgroups were compared on demographic, clinical, neuropsychological data and seizure outcome. TB was found in 39 (50%) patients, while TA was found in 32 (41%) patients, always ipsilateral to HS, with a considerable degree of overlap (69%) between TB and TA (p=0.01). Patients with temporopolar abnormalities did not significantly differ from those without TB or TA with regard to sex, age, age of epilepsy onset, duration of epilepsy, history of febrile convulsions or birth complications, side of surgery, seizure frequency at surgery, presence of GTCSs, and, in particular, seizure outcome. On the other hand, TB patients show a less frequent family history of epilepsy (p<.05) while age at epilepsy onset showed a trend to be lower in the TB group (p=.09). Patients with temporopolar atrophy did not significantly differ from those without TA on any variable, except for age at epilepsy onset, which was significantly lower for the TA group (p<.05). History of birth complications and longer duration of epilepsy also showed a trend to be associated with TA (p=.08). Multivariate analysis corroborated the association between temporopolar abnormalities and absence of family history of epilepsy and history of birth complications. High-field 3 T MRI in the preoperative workup for epilepsy surgery confirms that temporopolar abnormalities are frequent findings in TLE-HS patients and may be helpful to lateralize the epileptogenic zone. Their presence did not influence

  16. Mutations in KCNT1 cause a spectrum of focal epilepsies

    PubMed Central

    Møller, Rikke S.; Heron, Sarah E.; Larsen, Line H. G.; Lim, Chiao Xin; Ricos, Michael G.; Bayly, Marta A.; van Kempen, Marjan J. A.; Klinkenberg, Sylvia; Andrews, Ian; Kelley, Kent; Ronen, Gabriel M.; Callen, David; McMahon, Jacinta M.; Yendle, Simone C.; Carvill, Gemma L.; Mefford, Heather C.; Nabbout, Rima; Poduri, Annapurna; Striano, Pasquale; Baglietto, Maria G.; Zara, Federico; Smith, Nicholas J.; Pridmore, Clair; Gardella, Elena; Nikanorova, Marina; Dahl, Hans Atli; Gellert, Pia; Scheffer, Ingrid E.; Gunning, Boudewijn; Kragh-Olsen, Bente; Dibbens, Leanne M.

    2018-01-01

    Summary Autosomal dominant mutations in the sodium-gated potassium channel subunit gene KCNT1 have been associated with two distinct seizure syndromes, nocturnal frontal lobe epilepsy (NFLE) and malignant migrating focal seizures of infancy (MMFSI). To further explore the phenotypic spectrum associated with KCNT1, we examined individuals affected with focal epilepsy or an epileptic encephalopathy for mutations in the gene. We identified KCNT1 mutations in 12 previously unreported patients with focal epilepsy, multifocal epilepsy, cardiac arrhythmia, and in a family with sudden unexpected death in epilepsy (SUDEP), in addition to patients with NFLE and MMFSI. In contrast to the 100% penetrance so far reported for KCNT1 mutations, we observed incomplete penetrance. It is notable that we report that the one KCNT1 mutation, p.Arg398Gln, can lead to either of the two distinct phenotypes, ADNFLE or MMFSI, even within the same family. This indicates that genotype–phenotype relationships for KCNT1 mutations are not straightforward. We demonstrate that KCNT1 mutations are highly pleiotropic and are associated with phenotypes other than ADNFLE and MMFSI. KCNT1 mutations are now associated with Ohtahara syndrome, MMFSI, and nocturnal focal epilepsy. They may also be associated with multifocal epilepsy and cardiac disturbances. PMID:26122718

  17. Neurogenic function in rats with unilateral hippocampal sclerosis that experienced early-life status epilepticus

    PubMed Central

    Dunleavy, Mark; Schindler, Clara K; Shinoda, Sachiko; Crilly, Shane; Henshall, David C

    2014-01-01

    Status epilepticus in the adult brain invariably causes an increase in hippocampal neurogenesis and the appearance of ectopic cells and this has been implicated as a causal factor in epileptogenesis. The effect of status epilepticus on neurogenesis in the developing brain is less well characterized and models of early-life seizures typically do not reproduce the hippocampal damage common to human mesial temporal sclerosis. We recently reported that evoking status epilepticus by intra-amygdala microinjection of kainic acid in post-natal (P) day 10 rats caused substantial acute neuronal death within the ipsilateral hippocampus and rats later developed unilateral hippocampal sclerosis and spontaneous recurrent seizures. Here, we examined the expression of a selection of genes associated with neurogenesis and assessed neurogenic function in this model. Protein levels of several markers of neurogenesis including polysialic acid neural cell adhesion molecule, neuroD and doublecortin were reduced in the hippocampus three days after status epilepticus in P10 rats. In contrast, protein levels of neurogenesis markers were similar to control in rats at P55. Pulse-chase experiments using thymidine analogues suggested there was a reduction in new neurons at 72 h after status epilepticus in P10 rats, whereas numbers of new neurons labelled in epileptic rats at P55 with hippocampal sclerosis were similar to controls. The present study suggests that status epilepticus in the immature brain suppresses neurogenesis but the neurogenic potential is retained in animals that later develop hippocampal sclerosis. PMID:25755841

  18. Bumetanide Enhances Phenobarbital Efficacy in a Rat Model of Hypoxic Neonatal Seizures

    PubMed Central

    Cleary, Ryan T.; Sun, Hongyu; Huynh, Thanhthao; Manning, Simon M.; Li, Yijun; Rotenberg, Alexander; Talos, Delia M.; Kahle, Kristopher T.; Jackson, Michele; Rakhade, Sanjay N.; Berry, Gerard; Jensen, Frances E.

    2013-01-01

    Neonatal seizures can be refractory to conventional anticonvulsants, and this may in part be due to a developmental increase in expression of the neuronal Na+-K+-2 Cl− cotransporter, NKCC1, and consequent paradoxical excitatory actions of GABAA receptors in the perinatal period. The most common cause of neonatal seizures is hypoxic encephalopathy, and here we show in an established model of neonatal hypoxia-induced seizures that the NKCC1 inhibitor, bumetanide, in combination with phenobarbital is significantly more effective than phenobarbital alone. A sensitive mass spectrometry assay revealed that bumetanide concentrations in serum and brain were dose-dependent, and the expression of NKCC1 protein transiently increased in cortex and hippocampus after hypoxic seizures. Importantly, the low doses of phenobarbital and bumetanide used in the study did not increase constitutive apoptosis, alone or in combination. Perforated patch clamp recordings from ex vivo hippocampal slices removed following seizures revealed that phenobarbital and bumetanide largely reversed seizure-induced changes in EGABA. Taken together, these data provide preclinical support for clinical trials of bumetanide in human neonates at risk for hypoxic encephalopathy and seizures. PMID:23536761

  19. Seizures and electroencephalography findings in 61 patients with fetal alcohol spectrum disorders.

    PubMed

    Boronat, S; Vicente, M; Lainez, E; Sánchez-Montañez, A; Vázquez, E; Mangado, L; Martínez-Ribot, L; Del Campo, M

    2017-01-01

    Fetal alcohol spectrum disorders (FASD) cause neurodevelopmental abnormalities. However, publications about epilepsy and electroencephalographic features are scarce. In this study, we prospectively performed electroencephalography (EEG) and brain magnetic resonance (MR) imaging in 61 patients with diagnosis of FASD. One patient had multiple febrile seizures with normal EEGs. Fourteen children showed EEG anomalies, including slow background activity and interictal epileptiform discharges, focal and/or generalized, and 3 of them had epilepsy. In one patient, seizures were first detected during the EEG recording and one case had an encephalopathy with electrical status epilepticus during slow sleep (ESES). Focal interictal discharges in our patients did not imply the presence of underlying visible focal brain lesions in the neuroimaging studies, such as cortical dysplasia or polymicrogyria. However, they had nonspecific brain MR abnormalities, including corpus callosum hypoplasia, vermis hypoplasia or cavum septum pellucidum. The latter was significantly more frequent in the group with EEG abnormal findings (p < 0.01). Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  20. Characteristic MRI findings in hyperglycaemia-induced seizures: diagnostic value of contrast-enhanced fluid-attenuated inversion recovery imaging.

    PubMed

    Lee, E J; Kim, K K; Lee, E K; Lee, J E

    2016-12-01

    To describe characteristic magnetic resonance imaging (MRI) abnormalities in hyperglycaemia-induced seizures, and evaluate the diagnostic value of contrast-enhanced fluid-attenuated inversion recovery (FLAIR) imaging. Possible underlying mechanisms of this condition are also discussed. Eleven patients with hyperglycaemia-induced seizures and MRI abnormalities were retrospectively studied. Clinical manifestations, laboratory findings, MRI findings, and clinical outcomes were analysed. All patients, except one, presented with focal seizures, simple or complex partial seizures, or negative motor seizures. All patients had long-standing uncontrolled diabetes mellitus. The MRI abnormalities observed acutely were focal subcortical hypointensities on T2-weighted imaging and FLAIR imaging in all patients with overlying cortical gyral T2 hyperintensities in five. Focal overlying cortical or leptomeningeal enhancement on contrast-enhanced T1-weighted imaging or contrast-enhanced FLAIR imaging was observed in all patients. Contrast-enhanced FLAIR imaging was superior to contrast-enhanced T1-weighted imaging for detecting characteristic cortical or leptomeningeal enhancement. Diffusion-weighted imaging showed mildly restricted diffusion in four of five patients with cortical gyral T2 hyperintensity. In nine patients, the lesions were localised in the parietal or parieto-occipital lobes. The other two patients showed localised precentral gyral lesions. After treatment, the neurological symptoms, including the seizures, improved in all patients. On clinical recovery, the subcortical T2 hypointensity, gyral or leptomeningeal enhancement, and overlying cortical T2 hyperintensities resolved. Recognition of these radiological abnormalities in patients with hyperglycaemia-induced seizures is important in restricting unwarranted investigations and initiating early therapy. These patients generally have a good prognosis. Copyright © 2016 The Royal College of Radiologists. Published by

  1. Rates and predictors of seizure freedom in resective epilepsy surgery: an update

    PubMed Central

    Englot, Dario J.; Chang, Edward F.

    2017-01-01

    Epilepsy is a debilitating neurological disorder affecting approximately 1 % of the world’s population. Drug-resistant focal epilepsies are potentially surgically remediable. Although epilepsy surgery is dramatically underutilized among medically refractory patients, there is an expanding collection of evidence supporting its efficacy which may soon compel a paradigm shift. Of note is that a recent randomized controlled trial demonstrated that early resection leads to considerably better seizure outcomes than continued medical therapy in patients with pharmacoresistant temporal lobe epilepsy. In the present review, we provide a timely update of seizure freedom rates and predictors in resective epilepsy surgery, organized by the distinct pathological entities most commonly observed. Class I evidence, meta-analyses, and individual observational case series are considered, including the experiences of both our institution and others. Overall, resective epilepsy surgery leads to seizure freedom in approximately two thirds of patients with intractable temporal lobe epilepsy and about one half of individuals with focal neocortical epilepsy, although only the former observation is supported by class I evidence. Two common modifiable predictors of postoperative seizure freedom are early operative intervention and, in the case of a discrete lesion, gross total resection. Evidence-based practice guidelines recommend that epilepsy patients who continue to have seizures after trialing two or more medication regimens should be referred to a comprehensive epilepsy center for multidisciplinary evaluation, including surgical consideration. PMID:24497269

  2. Enhanced susceptibility to stress and seizures in GAD65 deficient mice

    PubMed Central

    Qi, Jin; Kim, Minjung; Sanchez, Russell; Ziaee, Saba M; Kohtz, Jhumku D

    2018-01-01

    Reduced gamma-aminobutyric acid (GABA) inhibition has been implicated in both anxiety and epilepsy. GAD65-/- (NOD/LtJ) mice have significantly decreased basal GABA levels in the brain and a lowered threshold for seizure generation. One fifth of GAD65 -/- mice experienced stress-induced seizures upon exposure to an open field at 4 weeks of age. In each successive week until 8 weeks of age, the latency to seizures decreased with prior seizure experience. 100% of GAD65-/- mice exhibited stress-induced seizures by the end of 8 weeks. GAD65-/- mice also exhibited marked impairment in open field exploratory behavior and deficits in spatial learning acquisition on a Barnes maze. Anxiety-like behavior in an open field was observed prior to seizure onset and was predictive of subsequent seizures. Immunohistochemical characterization of interneuron subtypes in GAD65-/- mice showed a selective decrease in GABA and neuropeptide Y (NPY) levels and no change in calbindin (CLB) or calretinin (CLR) immunoreactivity in the hippocampus. Stem cells from the medial ganglionic eminence (MGE) were injected into the hippocampal hilus to restore GABAergic interneurons. One week after transplantation, MGE-transplanted mice demonstrated significant seizure resistance compared to sham surgical controls. The percent area of GFP+ MGE graft in the hippocampus correlated significantly with the increase in seizure latency. Our data indicate that impaired GABAergic neurotransmission can cause anxiety-like behavior and stress-induced seizures that can be rescued by MGE stem cell transplantation. PMID:29377906

  3. Enhanced susceptibility to stress and seizures in GAD65 deficient mice.

    PubMed

    Qi, Jin; Kim, Minjung; Sanchez, Russell; Ziaee, Saba M; Kohtz, Jhumku D; Koh, Sookyong

    2018-01-01

    Reduced gamma-aminobutyric acid (GABA) inhibition has been implicated in both anxiety and epilepsy. GAD65-/- (NOD/LtJ) mice have significantly decreased basal GABA levels in the brain and a lowered threshold for seizure generation. One fifth of GAD65 -/- mice experienced stress-induced seizures upon exposure to an open field at 4 weeks of age. In each successive week until 8 weeks of age, the latency to seizures decreased with prior seizure experience. 100% of GAD65-/- mice exhibited stress-induced seizures by the end of 8 weeks. GAD65-/- mice also exhibited marked impairment in open field exploratory behavior and deficits in spatial learning acquisition on a Barnes maze. Anxiety-like behavior in an open field was observed prior to seizure onset and was predictive of subsequent seizures. Immunohistochemical characterization of interneuron subtypes in GAD65-/- mice showed a selective decrease in GABA and neuropeptide Y (NPY) levels and no change in calbindin (CLB) or calretinin (CLR) immunoreactivity in the hippocampus. Stem cells from the medial ganglionic eminence (MGE) were injected into the hippocampal hilus to restore GABAergic interneurons. One week after transplantation, MGE-transplanted mice demonstrated significant seizure resistance compared to sham surgical controls. The percent area of GFP+ MGE graft in the hippocampus correlated significantly with the increase in seizure latency. Our data indicate that impaired GABAergic neurotransmission can cause anxiety-like behavior and stress-induced seizures that can be rescued by MGE stem cell transplantation.

  4. Automated detection of videotaped neonatal seizures based on motion segmentation methods.

    PubMed

    Karayiannis, Nicolaos B; Tao, Guozhi; Frost, James D; Wise, Merrill S; Hrachovy, Richard A; Mizrahi, Eli M

    2006-07-01

    This study was aimed at the development of a seizure detection system by training neural networks using quantitative motion information extracted by motion segmentation methods from short video recordings of infants monitored for seizures. The motion of the infants' body parts was quantified by temporal motion strength signals extracted from video recordings by motion segmentation methods based on optical flow computation. The area of each frame occupied by the infants' moving body parts was segmented by direct thresholding, by clustering of the pixel velocities, and by clustering the motion parameters obtained by fitting an affine model to the pixel velocities. The computational tools and procedures developed for automated seizure detection were tested and evaluated on 240 short video segments selected and labeled by physicians from a set of video recordings of 54 patients exhibiting myoclonic seizures (80 segments), focal clonic seizures (80 segments), and random infant movements (80 segments). The experimental study described in this paper provided the basis for selecting the most effective strategy for training neural networks to detect neonatal seizures as well as the decision scheme used for interpreting the responses of the trained neural networks. Depending on the decision scheme used for interpreting the responses of the trained neural networks, the best neural networks exhibited sensitivity above 90% or specificity above 90%. The best among the motion segmentation methods developed in this study produced quantitative features that constitute a reliable basis for detecting myoclonic and focal clonic neonatal seizures. The performance targets of this phase of the project may be achieved by combining the quantitative features described in this paper with those obtained by analyzing motion trajectory signals produced by motion tracking methods. A video system based upon automated analysis potentially offers a number of advantages. Infants who are at risk for

  5. Anti-kindling Effect of Bezafibrate, a Peroxisome Proliferator-activated Receptors Alpha Agonist, in Pentylenetetrazole Induced Kindling Seizure Model

    PubMed Central

    Saha, Lekha; Bhandari, Swati; Bhatia, Alka; Banerjee, Dibyajyoti; Chakrabarti, Amitava

    2014-01-01

    Background and Purpose: Studies in the animals suggested that Peroxisome proliferators activated receptors (PPARs) may be involved in seizure control and selective agonists of PPAR α or PPAR γ raise seizure thresholds. The present study was contemplated with the aim of evaluating the anti kindling effects and the mechanism of bezafibrate, a Peroxisome proliferator-activated receptors α (PPAR-α) agonist in pentylenetetrazole (PTZ) induced kindling model of seizures in rats. Methods: In a PTZ kindled Wistar rat model, different doses of bezafibrate (100 mg/kg, 200 mg/kg and 300 mg/kg) were administered intraperitoneally 30 minutes before the PTZ injection. The PTZ injection was given on alternate day till the animal became fully kindled or till 10 weeks. The parameters measured were the latency to develop kindling and incidence of kindling, histopathological study of hippocampus, hippocampal lipid peroxidation studies, serum neuron specific enolase, and hippocampal DNA fragmentation study. Results: In this study, bezafibrate significantly reduced the incidence of kindling in PTZ treated rats and exhibited a marked prolongation in the latencies to seizures. In the present study bezafibrate decreased the thiobarbituric acid-reactive substance i.e. Malondialdehyde levels, increased the reduced glutathione levels, catalase and superoxide dismutase activity in the brain. This added to its additional neuroprotective effects. Bezafibrate also reduced the neuronal damage and apoptosis in hippocampal area of the brain. Therefore bezafibrate exerted anticonvulsant properties in PTZ induced kindling model in rats. Conclusions: These findings may provide insights into the understanding of the mechanism of bezafibrate as an anti kindling agent and could offer a useful support to the basic antiepileptic therapy in preventing the development of PTZ induced seizures, suggesting its potential for therapeutic applications in temporal lobe epilepsy. PMID:25625088

  6. Anticonvulsant effect of minocycline on pentylenetetrazole-induced seizure in mice: involvement of nitric oxide and N-methyl-D-aspartate receptor.

    PubMed

    Amini-Khoei, Hossein; Kordjazy, Nastaran; Haj-Mirzaian, Arya; Amiri, Shayan; Haj-Mirzaian, Arvin; Shirzadian, Armin; Hasanvand, Amin; Balali-Dehkordi, Shima; Hassanipoor, Mahsa; Dehpour, Ahmad Reza

    2018-03-20

    Anticonvulsant effects of minocycline have been explored recently. This study was designed to examine the anticonvulsant effect of acute administration of minocycline on pentylenetetrazole (PTZ)-induced seizures in mouse considering the possible role of nitric oxide (NO)/NMDA pathway. We induced seizure using intravenous administration of PTZ. Our results showed that acute administration of minocycline increased the seizure threshold. Furthermore, co-administration of sub-effective doses of the non-selective nitric oxide synthase (NOS) inhibitor, L-NAME (10 mg/kg) and the neuronal NOS inhibitor, 7-nitroindazole (40 mg/kg) enhanced the anticonvulsant effect of sub-effective dose of minocycline (40 mg/kg). We found that inducible NOS inhibitor, aminoguanidine (100 mg/kg), had no effect on the anti-seizure effect of minocycline. Moreover, L-arginine (60 mg/kg), as a NOS substrate, reduced the anticonvulsant effect of minocycline. We also demonstrated that pretreatment with NMDA receptor antagonists, ketamine (0.5 mg/kg) and MK-801 (0.05 mg/kg) increased the anticonvulsant effect of sub-effective dose of minocycline. Results showed that minocycline significantly decreased the hippocampal nitrite level. Furthermore, co-administration of nNOS inhibitor like NMDA receptor antagonists augmented the effect of minocycline on the hippocampal nitrite level. In conclusion, we revealed that anticonvulsant effect of minocycline might be, at least in part, due to decline in constitutive hippocampal nitric oxide activity as well as inhibition of NMDA receptors.

  7. Forecasting seizures in dogs with naturally occurring epilepsy.

    PubMed

    Howbert, J Jeffry; Patterson, Edward E; Stead, S Matt; Brinkmann, Ben; Vasoli, Vincent; Crepeau, Daniel; Vite, Charles H; Sturges, Beverly; Ruedebusch, Vanessa; Mavoori, Jaideep; Leyde, Kent; Sheffield, W Douglas; Litt, Brian; Worrell, Gregory A

    2014-01-01

    Seizure forecasting has the potential to create new therapeutic strategies for epilepsy, such as providing patient warnings and delivering preemptive therapy. Progress on seizure forecasting, however, has been hindered by lack of sufficient data to rigorously evaluate the hypothesis that seizures are preceded by physiological changes, and are not simply random events. We investigated seizure forecasting in three dogs with naturally occurring focal epilepsy implanted with a device recording continuous intracranial EEG (iEEG). The iEEG spectral power in six frequency bands: delta (0.1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-30 Hz), low-gamma (30-70 Hz), and high-gamma (70-180 Hz), were used as features. Logistic regression classifiers were trained to discriminate labeled pre-ictal and inter-ictal data segments using combinations of the band spectral power features. Performance was assessed on separate test data sets via 10-fold cross-validation. A total of 125 spontaneous seizures were detected in continuous iEEG recordings spanning 6.5 to 15 months from 3 dogs. When considering all seizures, the seizure forecasting algorithm performed significantly better than a Poisson-model chance predictor constrained to have the same time in warning for all 3 dogs over a range of total warning times. Seizure clusters were observed in all 3 dogs, and when the effect of seizure clusters was decreased by considering the subset of seizures separated by at least 4 hours, the forecasting performance remained better than chance for a subset of algorithm parameters. These results demonstrate that seizures in canine epilepsy are not randomly occurring events, and highlight the feasibility of long-term seizure forecasting using iEEG monitoring.

  8. Intravenous Carbamazepine for Adults With Seizures.

    PubMed

    Vickery, P Brittany; Tillery, Erika E; DeFalco, Alicia Potter

    2018-03-01

    To review the pharmacology, pharmacokinetics, efficacy, safety, dosage and administration, potential drug-drug interactions, and place in therapy of the intravenous (IV) formulation of carbamazepine (Carnexiv) for the treatment of seizures in adult patients. A comprehensive PubMed and EBSCOhost search (1945 to August 2017) was performed utilizing the keywords carbamazepine, Carnexiv, carbamazepine intravenous, IV carbamazepine, seizures, epilepsy, and seizure disorder. Additional data were obtained from literature review citations, manufacturer's product labeling, and Lundbeck website as well as Clinicaltrials.gov and governmental sources. All English-language trials evaluating IV carbamazepine were analyzed for this review. IV carbamazepine is FDA approved as temporary replacement therapy for treatment of adult seizures. Based on a phase I trial and pooled data from 2 open-label bioavailability studies comparing oral with IV dosing, there was no noted indication of loss of seizure control in patients switched to short-term replacement antiepileptic drug therapy with IV carbamazepine. The recommended dose of IV carbamazepine is 70% of the patient's oral dose, given every 6 hours via 30-minute infusions. The adverse effect profile of IV carbamazepine is similar to that of the oral formulation, with the exception of added infusion-site reactions. IV carbamazepine is a reasonable option for adults with generalized tonic-clonic or focal seizures, previously stabilized on oral carbamazepine, who are unable to tolerate oral medications for up to 7 days. Unknown acquisition cost and lack of availability in the United States limit its use currently.

  9. Hippocampal atrophy on MRI is predictive of histopathological patterns and surgical prognosis in mesial temporal lobe epilepsy with hippocampal sclerosis.

    PubMed

    Jardim, Anaclara Prada; Corso, Jeana Torres; Garcia, Maria Teresa Fernandes Castilho; Gaça, Larissa Botelho; Comper, Sandra Mara; Lancellotti, Carmen Lúcia Penteado; Centeno, Ricardo Silva; Carrete, Henrique; Cavalheiro, Esper Abrão; Scorza, Carla Alessandra; Yacubian, Elza Márcia Targas

    2016-12-01

    To correlate hippocampal volumes obtained from brain structural imaging with histopathological patterns of hippocampal sclerosis (HS), in order to predict surgical outcome. Patients with mesial temporal lobe epilepsy (MTLE) with HS were selected. Clinical data were assessed pre-operatively and surgical outcome in the first year post surgery. One block of mid hippocampal body was selected for HS classification according to ILAE criteria. NeuN-immunoreactive cell bodies were counted within hippocampal subfields, in four randomly visual fields, and cell densities were transformed into z-score values. FreeSurfer processing of 1.5T brain structural images was used for subcortical and cortical volumetric estimation of the ipsilateral hippocampus. Univariate analysis of variance and Pearson's correlation test were applied for statistical analyses. Sixty-two cases (31 female, 32 right HS) were included. ILAE type 1 HS was identified in 48 patients, type 2 in eight, type 3 in two, and four had no-HS. Better results regarding seizure control, i.e. ILAE 1, were achieved by patients with type 1 HS (58.3%). Patients with types 1 and 2 had smaller hippocampal volumes compared to those with no-HS (p<0.001 and p=0.004, respectively). Positive correlation was encountered between hippocampal volumes and CA1, CA3, CA4, and total estimated neuronal densities. CA2 was the only sector which did not correlate its neuronal density with hippocampal volume (p=0.390). This is the first study correlating hippocampal volume on MRI submitted to FreeSurfer processing with ILAE patterns of HS and neuronal loss within each hippocampal subfield, a fundamental finding to anticipate surgical prognosis for patients with drug-resistant MTLE and HS. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Thalamotemporal alteration and postoperative seizures in temporal lobe epilepsy

    PubMed Central

    Richardson, Mark P.; Schoene‐Bake, Jan‐Christoph; O'Muircheartaigh, Jonathan; Elkommos, Samia; Kreilkamp, Barbara; Goh, Yee Yen; Marson, Anthony G.; Elger, Christian; Weber, Bernd

    2015-01-01

    Objective There are competing explanations for persistent postoperative seizures after temporal lobe surgery. One is that 1 or more particular subtypes of mesial temporal lobe epilepsy (mTLE) exist that are particularly resistant to surgery. We sought to identify a common brain structural and connectivity alteration in patients with persistent postoperative seizures using preoperative quantitative magnetic resonance imaging and diffusion tensor imaging (DTI). Methods We performed a series of studies in 87 patients with mTLE (47 subsequently rendered seizure free, 40 who continued to experience postoperative seizures) and 80 healthy controls. We investigated the relationship between imaging variables and postoperative seizure outcome. All patients had unilateral temporal lobe seizure onset, had ipsilateral hippocampal sclerosis as the only brain lesion, and underwent amygdalohippocampectomy. Results Quantitative imaging factors found not to be significantly associated with persistent seizures were volumes of ipsilateral and contralateral mesial temporal lobe structures, generalized brain atrophy, and extent of resection. There were nonsignificant trends for larger amygdala and entorhinal resections to be associated with improved outcome. However, patients with persistent seizures had significant atrophy of bilateral dorsomedial and pulvinar thalamic regions, and significant alterations of DTI‐derived thalamotemporal probabilistic paths bilaterally relative to those patients rendered seizure free and controls, even when corrected for extent of mesial temporal lobe resection. Interpretation Patients with bihemispheric alterations of thalamotemporal structural networks may represent a subtype of mTLE that is resistant to temporal lobe surgery. Increasingly sensitive multimodal imaging techniques should endeavor to transform these group‐based findings to individualize prediction of patient outcomes. Ann Neurol 2015;77:760–774 PMID:25627477

  11. Etiology of hippocampal sclerosis

    PubMed Central

    Tsai, Meng-Han; Pardoe, Heath R.; Perchyonok, Yuliya; Fitt, Gregory J.; Scheffer, Ingrid E.; Berkovic, Samuel F.

    2013-01-01

    Objective: We sought evidence of a hereditary component for hippocampal sclerosis (HS) by determining whether close relatives of probands with temporal lobe epilepsy (TLE) with HS also had asymptomatic HS or subtle variation in hippocampal morphology. Methods: First-degree relatives from 15 families in which probands had TLE with HS and 32 age- and sex-matched controls were included in the study. Left and right hippocampal volumes and T2 relaxometry were measured using 3-tesla MRI. Results: Thirty-two asymptomatic first-degree relatives and 3 relatives with a history of seizures or epilepsy were studied. None of the first-degree relatives had HS on visual analysis and T2 relaxation times were normal, excluding the presence of HS. Mean hippocampal volume was smaller (6.4%) in asymptomatic relatives (2.94 ± 0.27 cm3, 95% confidence interval = 2.87–3.01) than in controls (3.14 ± 0.22 cm3, 95% confidence interval = 3.09–3.19, p < 0.005); the effect was greater in relatives of probands with a positive family history of epilepsy. The relatives also had more asymmetric hippocampi (asymmetric index 0.92 ± 0.05) than controls (0.96 ± 0.03, p = 0.001). Conclusions: Small asymmetric hippocampi in healthy relatives are likely to represent a familial developmental variant that may predispose to the formation of TLE with HS. The underlying histopathology of these small hippocampi is unknown. This observation may provide an imaging marker for future studies seeking susceptibility genes for HS. PMID:23749796

  12. Machine learning-based prediction of adverse drug effects: An example of seizure-inducing compounds.

    PubMed

    Gao, Mengxuan; Igata, Hideyoshi; Takeuchi, Aoi; Sato, Kaoru; Ikegaya, Yuji

    2017-02-01

    Various biological factors have been implicated in convulsive seizures, involving side effects of drugs. For the preclinical safety assessment of drug development, it is difficult to predict seizure-inducing side effects. Here, we introduced a machine learning-based in vitro system designed to detect seizure-inducing side effects. We recorded local field potentials from the CA1 alveus in acute mouse neocortico-hippocampal slices, while 14 drugs were bath-perfused at 5 different concentrations each. For each experimental condition, we collected seizure-like neuronal activity and merged their waveforms as one graphic image, which was further converted into a feature vector using Caffe, an open framework for deep learning. In the space of the first two principal components, the support vector machine completely separated the vectors (i.e., doses of individual drugs) that induced seizure-like events and identified diphenhydramine, enoxacin, strychnine and theophylline as "seizure-inducing" drugs, which indeed were reported to induce seizures in clinical situations. Thus, this artificial intelligence-based classification may provide a new platform to detect the seizure-inducing side effects of preclinical drugs. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  13. A new epileptic seizure classification based exclusively on ictal semiology.

    PubMed

    Lüders, H; Acharya, J; Baumgartner, C; Benbadis, S; Bleasel, A; Burgess, R; Dinner, D S; Ebner, A; Foldvary, N; Geller, E; Hamer, H; Holthausen, H; Kotagal, P; Morris, H; Meencke, H J; Noachtar, S; Rosenow, F; Sakamoto, A; Steinhoff, B J; Tuxhorn, I; Wyllie, E

    1999-03-01

    Historically, seizure semiology was the main feature in the differential diagnosis of epileptic syndromes. With the development of clinical EEG, the definition of electroclinical complexes became an essential tool to define epileptic syndromes, particularly focal epileptic syndromes. Modern advances in diagnostic technology, particularly in neuroimaging and molecular biology, now permit better definitions of epileptic syndromes. At the same time detailed studies showed that there does not necessarily exist a one-to-one relationship between epileptic seizures or electroclinical complexes and epileptic syndromes. These developments call for the reintroduction of an epileptic seizure classification based exclusively on clinical semiology, similar to the seizure classifications which were used by neurologists before the introduction of the modern diagnostic methods. This classification of epileptic seizures should always be complemented by an epileptic syndrome classification based on all the available clinical information (clinical history, neurological exam, ictal semiology, EEG, anatomical and functional neuroimaging, etc.). Such an approach is more consistent with mainstream clinical neurology and would avoid the current confusion between the classification of epileptic seizures (which in the International Seizure Classification is actually a classification of electroclinical complexes) and the classification of epileptic syndromes.

  14. Comparing neurostimulation technologies in refractory focal-onset epilepsy.

    PubMed

    Gooneratne, Inuka Kishara; Green, Alexander L; Dugan, Patricia; Sen, Arjune; Franzini, Angelo; Aziz, Tipu; Cheeran, Binith

    2016-11-01

    For patients with pharmacoresistant focal epilepsy in whom surgical resection of the epileptogenic focus fails or was not feasible in the first place, there were few therapeutic options. Increasingly, neurostimulation provides an alternative treatment strategy for these patients. Vagal nerve stimulation (VNS) is well established. Deep brain stimulation (DBS) and cortical responsive stimulation (CRS) are newer neurostimulation therapies with recently published long-term efficacy and safety data. In this literature review, we introduce these therapies to a non-specialist audience. Furthermore, we compare and contrast long-term (5-year) outcomes of newer neurostimulation techniques with the more established VNS. A search to identify all studies reporting long-term efficacy (>5 years) of VNS, CRS and DBS in patients with refractory focal/partial epilepsy was conducted using PubMed and Cochrane databases. The outcomes compared were responder rate, percentage seizure frequency reduction, seizure freedom, adverse events, neuropsychological outcome and quality of life. We identified 1 study for DBS, 1 study for CRS and 4 studies for VNS. All neurostimulation technologies showed long-term efficacy, with progressively better seizure control over time. Sustained improvement in quality of life measures was demonstrated in all modalities. Intracranial neurostimulation had a greater side effect profile compared with extracranial stimulation, though all forms of stimulation are safe. Methodological differences between the studies mean that direct comparisons are not straightforward. We have synthesised the findings of this review into a pragmatic decision tree, to guide the further management of the individual patient with pharmacoresistant focal-onset epilepsy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  15. Forecasting Seizures in Dogs with Naturally Occurring Epilepsy

    PubMed Central

    Stead, S. Matt; Brinkmann, Ben; Vasoli, Vincent; Crepeau, Daniel; Vite, Charles H.; Sturges, Beverly; Ruedebusch, Vanessa; Mavoori, Jaideep; Leyde, Kent; Sheffield, W. Douglas; Litt, Brian; Worrell, Gregory A.

    2014-01-01

    Seizure forecasting has the potential to create new therapeutic strategies for epilepsy, such as providing patient warnings and delivering preemptive therapy. Progress on seizure forecasting, however, has been hindered by lack of sufficient data to rigorously evaluate the hypothesis that seizures are preceded by physiological changes, and are not simply random events. We investigated seizure forecasting in three dogs with naturally occurring focal epilepsy implanted with a device recording continuous intracranial EEG (iEEG). The iEEG spectral power in six frequency bands: delta (0.1–4 Hz), theta (4–8 Hz), alpha (8–12 Hz), beta (12–30 Hz), low-gamma (30–70 Hz), and high-gamma (70–180 Hz), were used as features. Logistic regression classifiers were trained to discriminate labeled pre-ictal and inter-ictal data segments using combinations of the band spectral power features. Performance was assessed on separate test data sets via 10-fold cross-validation. A total of 125 spontaneous seizures were detected in continuous iEEG recordings spanning 6.5 to 15 months from 3 dogs. When considering all seizures, the seizure forecasting algorithm performed significantly better than a Poisson-model chance predictor constrained to have the same time in warning for all 3 dogs over a range of total warning times. Seizure clusters were observed in all 3 dogs, and when the effect of seizure clusters was decreased by considering the subset of seizures separated by at least 4 hours, the forecasting performance remained better than chance for a subset of algorithm parameters. These results demonstrate that seizures in canine epilepsy are not randomly occurring events, and highlight the feasibility of long-term seizure forecasting using iEEG monitoring. PMID:24416133

  16. Spatiotemporal differences in the c-fos pathway between C57BL/6J and DBA/2J mice following flurothyl-induced seizures: a dissociation of hippocampal Fos from seizure activity

    PubMed Central

    Kadiyala, Sridhar B.; Papandrea, Dominick; Tuz, Karina; Anderson, Tara M.; Jayakumar, Sachidhanand; Herron, Bruce J.; Ferland, Russell J.

    2014-01-01

    Significant differences in seizure characteristics between inbred mouse strains highlight the importance of genetic predisposition to epilepsy. Here, we examined the genetic differences between the seizure-resistant C57BL/6J (B6) mouse strain and the seizure-susceptible DBA/2J (D2) strain in the phospho-Erk and Fos pathways to examine seizure-induced neuronal activity to uncover potential mechanistic correlates to these disparate seizure responsivities. Expression of neural activity markers was examined following 1, 5, or 8 seizures, or after 8 seizures, a 28 day rest period, and a final flurothyl rechallenge. Two brain regions, the hippocampus and ventromedial nucleus of the hypothalamus (VMH), had significantly different Fos expression profiles following seizures. Fos expression was highly robust in B6 hippocampus following one seizure and remained elevated following multiple seizures. Conversely, there was an absence of Fos (and phospho-Erk) expression in D2 hippocampus following one generalized seizure that increased with multiple seizures. This lack of Fos expression occurred despite intracranial electroencephalographic recordings indicating that the D2 hippocampus propagated ictal discharge during the first flurothyl seizure suggesting a dissociation of seizure discharge from Fos and phospho-Erk expression. Global transcriptional analysis confirmed a dysregulation of the c-fos pathway in D2 mice following 1 seizure. Moreover, global analysis of RNA expression differences between B6 and D2 hippocampus revealed a unique pattern of transcripts that were co-regulated with Fos in D2 hippocampus following 1 seizure. These expression differences could, in part, account for D2’s seizure susceptibility phenotype. Following 8 seizures, a 28 day rest period, and a final flurothyl rechallenge, ~85% of B6 mice develop a more complex seizure phenotype consisting of a clonic-forebrain seizure that uninterruptedly progresses into a brainstem seizure. This seizure phenotype

  17. Spatiotemporal differences in the c-fos pathway between C57BL/6J and DBA/2J mice following flurothyl-induced seizures: A dissociation of hippocampal Fos from seizure activity.

    PubMed

    Kadiyala, Sridhar B; Papandrea, Dominick; Tuz, Karina; Anderson, Tara M; Jayakumar, Sachidhanand; Herron, Bruce J; Ferland, Russell J

    2015-01-01

    Significant differences in seizure characteristics between inbred mouse strains highlight the importance of genetic predisposition to epilepsy. Here, we examined the genetic differences between the seizure-resistant C57BL/6J (B6) mouse strain and the seizure-susceptible DBA/2J (D2) strain in the phospho-Erk and Fos pathways to examine seizure-induced neuronal activity to uncover potential mechanistic correlates to these disparate seizure responsivities. Expression of neural activity markers was examined following 1, 5, or 8 seizures, or after 8 seizures, a 28 day rest period, and a final flurothyl rechallenge. Two brain regions, the hippocampus and ventromedial nucleus of the hypothalamus (VMH), had significantly different Fos expression profiles following seizures. Fos expression was highly robust in B6 hippocampus following one seizure and remained elevated following multiple seizures. Conversely, there was an absence of Fos (and phospho-Erk) expression in D2 hippocampus following one generalized seizure that increased with multiple seizures. This lack of Fos expression occurred despite intracranial electroencephalographic recordings indicating that the D2 hippocampus propagated ictal discharge during the first flurothyl seizure suggesting a dissociation of seizure discharge from Fos and phospho-Erk expression. Global transcriptional analysis confirmed a dysregulation of the c-fos pathway in D2 mice following 1 seizure. Moreover, global analysis of RNA expression differences between B6 and D2 hippocampus revealed a unique pattern of transcripts that were co-regulated with Fos in D2 hippocampus following 1 seizure. These expression differences could, in part, account for D2's seizure susceptibility phenotype. Following 8 seizures, a 28 day rest period, and a final flurothyl rechallenge, ∼85% of B6 mice develop a more complex seizure phenotype consisting of a clonic-forebrain seizure that uninterruptedly progresses into a brainstem seizure. This seizure phenotype

  18. Alterations of network synchrony after epileptic seizures: An analysis of post-ictal intracranial recordings in pediatric epilepsy patients.

    PubMed

    Tomlinson, Samuel B; Khambhati, Ankit N; Bermudez, Camilo; Kamens, Rebecca M; Heuer, Gregory G; Porter, Brenda E; Marsh, Eric D

    2018-07-01

    Post-ictal EEG alterations have been identified in studies of intracranial recordings, but the clinical significance of post-ictal EEG activity is undetermined. The purpose of this study was to examine the relationship between peri-ictal EEG activity, surgical outcome, and extent of seizure propagation in a sample of pediatric epilepsy patients. Intracranial EEG recordings were obtained from 19 patients (mean age = 11.4 years, range = 3-20 years) with 57 seizures used for analysis (mean = 3.0 seizures per patient). For each seizure, 3-min segments were extracted from adjacent pre-ictal and post-ictal epochs. To compare physiology of the epileptic network between epochs, we calculated the relative delta power (Δ) using discrete Fourier transformation and constructed functional networks based on broadband connectivity (conn). We investigated differences between the pre-ictal (Δ pre , conn pre ) and post-ictal (Δ post , conn post ) segments in focal-network (i.e., confined to seizure onset zone) versus distributed-network (i.e., diffuse ictal propagation) seizures. Distributed-network (DN) seizures exhibited increased post-ictal delta power and global EEG connectivity compared to focal-network (FN) seizures. Following DN seizures, patients with seizure-free outcomes exhibited a 14.7% mean increase in delta power and an 8.3% mean increase in global connectivity compared to pre-ictal baseline, which was dramatically less than values observed among seizure-persistent patients (29.6% and 47.1%, respectively). Post-ictal differences between DN and FN seizures correlate with post-operative seizure persistence. We hypothesize that post-ictal deactivation of subcortical nuclei recruited during seizure propagation may account for this result while lending insights into mechanisms of post-operative seizure recurrence. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Hippocampal CA1 Kindling but Not Long-Term Potentiation Disrupts Spatial Memory Performance

    ERIC Educational Resources Information Center

    Leung, L. Stan; Shen, Bixia

    2006-01-01

    Long-term synaptic enhancement in the hippocampus has been suggested to cause deficits in spatial performance. Synaptic enhancement has been reported after hippocampal kindling that induced repeated electrographic seizures or afterdischarges (ADs) and after long-term potentiation (LTP) defined as synaptic enhancement without ADs. We studied…

  20. On the nature of seizure dynamics

    PubMed Central

    Stacey, William C.; Quilichini, Pascale P.; Ivanov, Anton I.

    2014-01-01

    Seizures can occur spontaneously and in a recurrent manner, which defines epilepsy; or they can be induced in a normal brain under a variety of conditions in most neuronal networks and species from flies to humans. Such universality raises the possibility that invariant properties exist that characterize seizures under different physiological and pathological conditions. Here, we analysed seizure dynamics mathematically and established a taxonomy of seizures based on first principles. For the predominant seizure class we developed a generic model called Epileptor. As an experimental model system, we used ictal-like discharges induced in vitro in mouse hippocampi. We show that only five state variables linked by integral-differential equations are sufficient to describe the onset, time course and offset of ictal-like discharges as well as their recurrence. Two state variables are responsible for generating rapid discharges (fast time scale), two for spike and wave events (intermediate time scale) and one for the control of time course, including the alternation between ‘normal’ and ictal periods (slow time scale). We propose that normal and ictal activities coexist: a separatrix acts as a barrier (or seizure threshold) between these states. Seizure onset is reached upon the collision of normal brain trajectories with the separatrix. We show theoretically and experimentally how a system can be pushed toward seizure under a wide variety of conditions. Within our experimental model, the onset and offset of ictal-like discharges are well-defined mathematical events: a saddle-node and homoclinic bifurcation, respectively. These bifurcations necessitate a baseline shift at onset and a logarithmic scaling of interspike intervals at offset. These predictions were not only confirmed in our in vitro experiments, but also for focal seizures recorded in different syndromes, brain regions and species (humans and zebrafish). Finally, we identified several possible biophysical

  1. Temporal seizure focus and status epilepticus are associated with high-sensitive troponin I elevation after epileptic seizures.

    PubMed

    Chatzikonstantinou, Anastasios; Ebert, Anne D; Hennerici, Michael G

    2015-09-01

    Postictal elevation of high-sensitive troponin I (TNI), a highly specific biomarker for myocardial ischemia, has been reported. We aimed at evaluating its association of high-sensitive troponin I (TNI) with seizure type and focus, as well as vascular risk factors. TNI was measured in 247 patients admitted to our clinic via the emergency room with an acute epileptic seizure. TNI control measurements were performed in 61.5% of cases. All patients underwent electroencephalography and cerebral imaging. Seizure focus - when possible - was determined using results from these examinations as well as clinical data. Of 247 patients, 133 (53.8%) were men, the mean age was 59 ± 18 years. 70 (28.3%) patients had focal and 177 (71.7%) generalized seizures. Status epilepticus was present in 38 cases (15.4%). Mean TNI was 0.05 ± 0.17. TNI was elevated in 27 patients (10.9%). Higher age, status epilepticus and temporal seizure focus were significantly associated with TNI elevation in multivariate analysis. In 21 (13.8%) of the patients with TNI control measurement, TNI was continuously elevated. Higher age and temporal seizure focus were significantly associated with continuously high TNI. Coronary heart disease and vascular risk factors were significantly associated with high TNI only in univariate analysis. No patient had a symptomatic myocardial ischemia. Postictal TNI elevation is relatively common in older patients with status epilepticus or temporal seizure focus. These data support the concept of relevant and possibly dangerous ictal effects on cardiac function especially in temporal lobe seizures. Although the risk of manifest postictal myocardial infarction seems to be very low, selected patients could profit from closer monitoring. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Seizure Dynamics of Coupled Oscillators with Epileptor Field Model

    NASA Astrophysics Data System (ADS)

    Zhang, Honghui; Xiao, Pengcheng

    The focus of this paper is to investigate the dynamics of seizure activities by using the Epileptor coupled model. Based on the coexistence of seizure-like event (SLE), refractory status epilepticus (RSE), depolarization block (DB), and normal state, we first study the dynamical behaviors of two coupled oscillators in different activity states with Epileptor model by linking them with slow permittivity coupling. Our research has found that when one oscillator in normal states is coupled with any oscillator in SLE, RSE or DB states, these two oscillators can both evolve into SLE states under appropriate coupling strength. And then these two SLE oscillators can perform epileptiform synchronization or epileptiform anti-synchronization. Meanwhile, SLE can be depressed when considering the fast electrical or chemical coupling in Epileptor model. Additionally, a two-dimensional reduced model is also given to show the effect of coupling number on seizures. Those results can help to understand the dynamical mechanism of the initiation, maintenance, propagation and termination of seizures in focal epilepsy.

  3. High-Frequency Oscillations and Seizure Generation in Neocortical Epilepsy

    ERIC Educational Resources Information Center

    Worrell, Greg A.; Parish, Landi; Cranstoun, Stephen D.; Jonas, Rachel; Baltuch, Gordon; Litt, Brian

    2004-01-01

    Neocortical seizures are often poorly localized, explosive and widespread at onset, making them poorly amenable to epilepsy surgery in the absence of associated focal brain lesions. We describe, for the first time in an unselected group of patients with neocortical epilepsy, the finding that high-frequency (60--100 Hz) epileptiform oscillations…

  4. Epilepsy with dual pathology: surgical treatment of cortical dysplasia accompanied by hippocampal sclerosis.

    PubMed

    Kim, Dong W; Lee, Sang K; Nam, Hyunwoo; Chu, Kon; Chung, Chun K; Lee, Seo-Young; Choe, Geeyoung; Kim, Hyun K

    2010-08-01

    The presence of two or more epileptogenic pathologies in patients with epilepsy is often observed, and the coexistence of focal cortical dysplasia (FCD) with hippocampal sclerosis (HS) is one of the most frequent clinical presentations. Although surgical resection has been an important treatment for patients with refractory epilepsy associated with FCD, there are few studies on the surgical treatment of FCD accompanied by HS, and treatment by resection of both neocortical dysplastic tissue and hippocampus is still controversial. We retrospectively recruited epilepsy patients who had undergone surgical treatment for refractory epilepsy with the pathologic diagnosis of FCD and the radiologic evidence of HS. We evaluated the prognostic roles of clinical factors, various diagnostic modalities, surgical procedures, and the severity of pathology. A total of 40 patients were included, and only 35.0% of patients became seizure free. Complete resection of the epileptogenic area (p = 0.02), and the presence of dysmorphic neurons or balloon cells on histopathology (p = 0.01) were associated with favorable surgical outcomes. Patients who underwent hippocampal resection were more likely to have a favorable surgical outcome (p = 0.02). We show that patients with complete resection of epileptogenic area, the presence of dysmorphic neurons or balloon cells on histopathology, or resection of hippocampus have a higher chance of a favorable surgical outcome. We believe that this observation is useful in planning of surgical procedures and predicting the prognoses of individual patients with FCD patients accompanied by HS. Wiley Periodicals, Inc. © 2009 International League Against Epilepsy.

  5. Focal cortical dysplasias: surgical outcome in 67 patients in relation to histological subtypes and dual pathology.

    PubMed

    Fauser, Susanne; Schulze-Bonhage, Andreas; Honegger, Juergen; Carmona, Hans; Huppertz, Hans-Juergen; Pantazis, Georgios; Rona, Sabine; Bast, Thomas; Strobl, Karl; Steinhoff, Bernhard J; Korinthenberg, Rudolf; Rating, Dietz; Volk, Benedikt; Zentner, Josef

    2004-11-01

    The purpose of this study was to assess whether the histological subtype of focal cortical dysplasia and dual pathology affect surgical outcome in patients with medically intractable epilepsy due to focal cortical dysplasia (FCD). We retrospectively analysed the outcome of 67 patients from 2 to 66 years of age at follow-up periods of 6 to 48 months after epilepsy surgery. Histological subtypes were classified according to Palmini and included a few cases with mild histological abnormalities corresponding to the definition of mild malformations of cortical development. The seizure outcome was classified according to Engel and evaluated at the last follow-up visit as well as at follow-up periods of 12 and 24 months after surgery. The outcome in patients with FCD and additional hippocampal pathology (dual pathology) was analysed separately. Distribution of histological subtypes differed in temporal and extratemporal localization, with a significantly higher extratemporal prevalence of FCD type 2. There was a tendency towards better postsurgical outcome related to the last follow-up visit in patients with more subtle abnormalities classified as mild malformations of cortical development (mMCD) (63% Engel Ia), FCD type 1a (67% Engel Ia) and FCD type 1b (55% Engel Ia) compared with patients with FCD type 2a (43% Engel Ia) and FCD type 2b (Taylor type) (50% Engel Ia). Considering the outcome at follow-up periods over 12 and 24 months, complete seizure-freedom was achieved significantly more often in patients with FCD type 1 and mMCD than with FCD type 2, and seizure reduction by less than 75% (Engel IV) occurred in more patients with FCD type 2a compared with the other subgroups. This tendency was seen in the whole patient group and in the extratemporal subgroup. Patients with dual pathology almost always had temporal lobe epilepsy; the outcome in this patient group was generally favourable (66% complete seizure-freedom at the last follow-up visit). The outcome remained

  6. Investigation of hypoxia-inducible factor-1α in hippocampal sclerosis: a postmortem study.

    PubMed

    Feast, Alexandra; Martinian, Lillian; Liu, Joan; Catarino, Claudia B; Thom, Maria; Sisodiya, Sanjay M

    2012-08-01

    Hypoxia-inducible factor-1α (HIF-1α) is involved in critical aspects of cell survival in response to hypoxia and regulates vascular endothelial growth factor (VEGF) expression. Previous experimental and human studies in epilepsy show up-regulation of VEGF following seizures, although expression of HIF-1α as its potential regulator has not been explored. We used a postmortem (PM) series from patients with epilepsy and hippocampal sclerosis (HS) to investigate patterns of expression of HIF-1α and VEGF and their potential contribution to neuroprotection. In 33 PMs (17 cases with unilateral HS, 3 with bilateral HS, 3 with No-HS, and 10 controls), we quantified neuronal immunolabeling for HIF-1α and VEGF in hippocampal subfields. HIF-1α- and VEGF-immunopositive hippocampal neurones were observed in HS, No-HS, and also in control cases; there was no significant difference in overall labeling between epilepsy cases and controls. In positive cases, HIF-1α and VEGF neuronal labeling localized primarily in CA1, CA4, and CA3 subfields in all groups; significantly more positive neurons were seen in the entorhinal cortex in epilepsy cases (p < 0.05). Labeling lateralized to the side of sclerosis in unilateral HS cases, with significant differences between hemispheres (p < 0.05). There was a trend for high HIF-1α labeling scores in patients with Dravet syndrome without HS and sudden unexpected death in epilepsy (SUDEP) cases, and lower scores with long seizure-free periods prior to death. Hippocampal HIF-1α and VEGF labeling showed a significant correlation. There was neuronal colocalization of HIF-1α and VEGF. Regional expression patterns are in keeping with seizure-related activation of HIF-1α and VEGF. The prominent expression in non-HS cases could support an overall neuroprotective effect. Correlation between HIF-1α and VEGF neuronal immunolabeling supports HIF-1α-mediated induction of VEGF in epilepsy. Wiley Periodicals, Inc. © 2012 International League

  7. DEPDC5 takes a second hit in familial focal epilepsy.

    PubMed

    Anderson, Matthew P

    2018-04-30

    Loss-of-function mutations in a single allele of the gene encoding DEP domain-containing 5 protein (DEPDC5) are commonly linked to familial focal epilepsy with variable foci; however, a subset of patients presents with focal cortical dysplasia that is proposed to result from a second-hit somatic mutation. In this issue of the JCI, Ribierre and colleagues provide several lines of evidence to support second-hit DEPDC5 mutations in this disorder. Moreover, the authors use in vivo, in utero electroporation combined with CRISPR-Cas9 technology to generate a murine model of the disease that recapitulates human manifestations, including cortical dysplasia-like changes, focal seizures, and sudden unexpected death. This study provides important insights into familial focal epilepsy and provides a preclinical model for evaluating potential therapies.

  8. Impaired extinction of fear and maintained amygdala-hippocampal theta synchrony in a mouse model of temporal lobe epilepsy.

    PubMed

    Lesting, Jörg; Geiger, Matthias; Narayanan, Rajeevan T; Pape, Hans-Christian; Seidenbecher, Thomas

    2011-02-01

    The relationship between epilepsy and fear has received much attention. However, seizure-modulated fear and physiologic or structural correlates have not been examined systematically, and the underlying basics of network levels remain unclear to date. Therefore, this project was set up to characterize the neurophysiologic basis of seizure-related fear and the contribution of the amygdala-hippocampus system. The experimental strategy was composed of the following steps: (1) use of the mouse pilocarpine model of temporal lobe epilepsy (TLE); (2) behavioral analyses of anxiety states in the elevated plus maze test, light-dark avoidance test, and Pavlovian fear conditioning; and (3) probing neurophysiologic activity patterns in amygdala-hippocampal circuits in freely behaving mice. Our results displayed no significant differences in basic anxiety levels comparing mice that developed spontaneous recurrent seizures (SRS) and controls. Furthermore, conditioned fear memory retrieval was not influenced in SRS mice. However, during fear memory extinction, SRS mice showed an extended freezing behavior and a maintained amygdala-hippocampal theta frequency synchronization compared to controls. These results indicate specific alterations in conditioned fear behavior and related neurophysiologic activities in the amygdala-hippocampal network contributing to impaired fear memory extinction in mice with TLE. Clinically, the nonextinguished fear memories may well contribute to the experience of fear in patients with TLE. Wiley Periodicals, Inc. © 2010 International League Against Epilepsy.

  9. [Machine Learning-based Prediction of Seizure-inducing Action as an Adverse Drug Effect].

    PubMed

    Gao, Mengxuan; Sato, Motoshige; Ikegaya, Yuji

    2018-01-01

     During the preclinical research period of drug development, animal testing is widely used to help screen out a drug's dangerous side effects. However, it remains difficult to predict side effects within the central nervous system. Here, we introduce a machine learning-based in vitro system designed to detect seizure-inducing side effects before clinical trial. We recorded local field potentials from the CA1 alveus in acute mouse neocortico-hippocampal slices that were bath-perfused with each of 14 different drugs, and at 5 different concentrations of each drug. For each of these experimental conditions, we collected seizure-like neuronal activity and merged their waveforms as one graphic image, which was further converted into a feature vector using Caffe, an open framework for deep learning. In the space of the first two principal components, the support vector machine completely separated the vectors (i.e., doses of individual drugs) that induced seizure-like events, and identified diphenhydramine, enoxacin, strychnine and theophylline as "seizure-inducing" drugs, which have indeed been reported to induce seizures in clinical situations. Thus, this artificial intelligence-based classification may provide a new platform to pre-clinically detect seizure-inducing side effects of drugs.

  10. Autonomic symptoms during childhood partial epileptic seizures.

    PubMed

    Fogarasi, András; Janszky, József; Tuxhorn, Ingrid

    2006-03-01

    To analyze systematically the occurrence and age dependence as well as the localizing and lateralizing value of ictal autonomic symptoms (ASs) during childhood partial epilepsies and to compare our results with those of earlier adult studies. Five hundred fourteen video-recorded seizures of 100 consecutive children 12 years or younger with partial epilepsy and seizure-free postoperative outcome were retrospectively analyzed. Sixty patients produced at least one AS; 43 (70%) of 61 with temporal and 17 (44%) of 39 with extratemporal lobe epilepsy (p=0.012). Apnea/bradypnea occurred more frequently in younger children (p<0.01), whereas the presence of other ASs was neither age nor gender related. Postictal coughing (p<0.01) and epigastric aura (p<0.05) localized to the temporal lobe, whereas no ASs lateralized to the seizure-onset zone. Our study shows that ASs are common in childhood focal epilepsies, appearing in infants and young children, too. As in adults, childhood central autonomic networks might have a close connection to temporal lobe structures but do not lateralize the seizure-onset zone. To our knowledge, this is the first study comprehensively assessing ASs in childhood epilepsy.

  11. Calcified neurocysticercosis lesions and hippocampal sclerosis: potential dual pathology?

    PubMed

    Rathore, Chaturbhuj; Thomas, Bejoy; Kesavadas, Chandrasekharan; Radhakrishnan, Kurupath

    2012-04-01

    In areas where cysticercosis is endemic, calcified neurocysticercosis lesion(s) (CNL) and hippocampal sclerosis (HS) commonly coexist in patients with localization-related epilepsies. To understand the pathogenesis of HS associated with CNL, we compared the characteristics of three groups of patients with antiepileptic drug-resistant epilepsies: CNL with HS, CNL without HS (CNL alone), and HS without CNL (HS alone). In comparison to patients with CNL alone, those with CNL with HS had CNL more frequently located in the ipsilateral temporal lobe. Those with CNL with HS had a lower incidence of febrile seizures, older age at initial precipitating injury and at onset of habitual complex partial seizures, and more frequent clustering of seizures and extratemporal/bitemporal interictal epileptiform discharges as compared to patients with HS alone. Our study illustrates that HS associated with CNL might have a different pathophysiologic basis as compared to classical HS. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

  12. Lacosamide as an adjunctive therapy in pediatric patients with refractory focal epilepsy.

    PubMed

    Kim, Jon Soo; Kim, Hunmin; Lim, Byung Chan; Chae, Jong-Hee; Choi, Jieun; Kim, Ki Joong; Hwang, Yong Seung; Hwang, Hee

    2014-06-01

    To evaluate the efficacy and safety of lacosamide in pediatric patients with refractory focal epilepsy. We reviewed retrospectively the medical records of children younger than 18 years of age treated at Seoul National University Bundang Hospital, in whom oral lacosamide was used as an adjunctive treatment for refractory focal epilepsy. Clinical information regarding the patients' epilepsy and the outcome of lacosamide treatment was gathered and analyzed. Twenty-one patients (16 boys, 5 girls) were included, with a median age of 13.9 (range, 1.2-17.9) years. The mean number of concomitant antiepileptic drugs was 3.0 (range, 1-6) and the mean duration of follow-up was 10.1 (range, 6.1-13.0) months. The mean maintenance dose of lacosamide was 5.4 (range, 1.4-9.8) mg/kg/day. Fourteen patients (67%) were responders; four of these were seizure free at the last follow-up. Seven patients (33%) were nonresponders: two of these presented with <50% seizure reduction and five showed no change in seizure frequency. Two patients (10%) discontinued oral lacosamide because of adverse events (aggressive behavior and depression). Mild transient treatment-related adverse events were observed in eight of the 21 patients (38%). Lacosamide represents a useful drug that is effective for a wide range of pediatric refractory focal epilepsy and is well tolerated. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  13. Epileptogenicity of cortical dysplasia in temporal lobe dual pathology: an electrophysiological study with invasive recordings.

    PubMed

    Fauser, Susanne; Schulze-Bonhage, Andreas

    2006-01-01

    Hippocampal sclerosis is often associated with macroscopic or microscopic dysplasia in the temporal neocortex (TN). The relevance of such a dual pathology with regard to epileptogenesis is unclear. This study investigates the role of both pathologies in the generation of ictal and interictal activity. Ictal (113 seizures) and interictal data from invasive EEG recordings with simultaneous depth electrodes in the hippocampus and subdural electrodes over the TN were analysed retrospectively in 12 patients with variable degrees of hippocampal sclerosis and different types of histologically confirmed temporal cortical dysplasia [all male, age at epilepsy onset <1-29 years (mean 9.6 years), age when invasive recordings were performed 6-50 years (mean 28.2 years)]. Of the seizures 41.3% arose from the amygdala/hippocampus complex (AHC), 34.7% from the TN, 22% were simultaneously recorded from AHC and TN (indeterminate seizure onset), and 2% from other regions. In three patients, seizure onset was recorded only from the AHC. In patients with severe hippocampal sclerosis only 12% of the seizures arose from the TN, whereas in patients with mild hippocampal sclerosis 58% arose from the TN. The type of cortical dysplasia, however, did not predict seizure onset in the AHC or TN. Propagation time from the TN to the AHC tended to be shorter (mean 7.4 s) than vice versa (mean 13.7 s). The most common initial ictal patterns in the AHC were rhythmic beta activity (<25 Hz) and repetitive sharp waves, and in the TN were fast activity (>25 Hz) and repetitive sharp waves. The interictal patterns over the TN were similar to those seen over extratemporal focal cortical dysplasias. Simultaneous recordings from the hippocampus and the TN strongly suggest that dysplastic tissue in the TN is often epileptogenic. The quantitative contribution of the hippocampus to seizure generation corresponded with the degree of hippocampal pathology, whereas different subtypes of cortical dysplasia did not

  14. Corpora amylacea in the neocortex in patients with temporal lobe epilepsy and focal cortical dysplasia.

    PubMed

    Estupiñán-Díaz, B O; Morales-Chacón, L M; García-Maeso, I; Lorigados-Pedre, L; Báez-Martín, M; García-Navarro, M E; Trápaga-Quincoses, O; Quintanal-Cordero, N; Prince-López, J; Bender-del Busto, J E

    2015-03-01

    Corpora amylacea (CoA) are present in about 60% of atrophic hippocampi resected from patients with drug resistant temporal lobe epilepsy (DRTLE). They have also been described in the lateral temporal neocortex, although less frequently. The objective is to measure the presence, distribution and density of CoA in the lateral temporal lobes of patients with DRTLE and focal cortical dysplasia (FCD), also examining how CoA density may be linked to demographic and clinical traits. Resected tissue from 35 patients was analysed. CoA density was assessed with a semi-quantitative scale according to the criteria established by Cherian et al. Presence of CoA in the neocortex of 9 patients was associated with hippocampal sclerosis (FCD type iiia, 7 cases), disembryoplastic neuroepithelial tumour (FCD type iiib, 1 case), and cavernous angioma (FCD type iiic, 1 case). The meningeal surface (MS) was involved in all cases, and 8 cases displayed CoA in the cerebral parenchyma (white matter) and around blood vessels. CoA density on the MS showed a negative correlation with age at seizure onset (r = -0.828, P<.05) and a positive correlation with disease duration (r = 0.678, P<.05) but not with postoperative clinical outcome. Patients with DRTLE and a primary lesion (hippocampal sclerosis, tumour, vascular malformation) associated with mild FCD were shown to have CoA deposits in the neocortex. No association was found between presence of CoA and clinical outcome one year after surgery. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  15. HOMEOSTATIC REGULATION OF KCC2 ACTIVITY BY THE ZINC RECEPTOR mZnR/GPR39 DURING SEIZURES

    PubMed Central

    Gilad, David; Shorer, Sharon; Ketzef, Maya; Friedman, Alon; Sekler, Israel; Aizenman, Elias; Hershfinkel, Michal

    2015-01-01

    The aim of this study was to investigate the role of the synaptic metabotropic zinc receptor mZnR/GPR39 in physiological adaptation to epileptic seizures. We previously demonstrated that synaptic activation of mZnR/GPR39 enhances inhibitory drive in the hippocampus by upregulating neuronal K+/Cl− co-transporter 2 (KCC2) activity. Here, we first show that mZnR/GPR39 knockout (KO) adult mice have dramatically enhanced susceptibility to seizures triggered by a single intraperitoneal injection of kainic acid, when compared to wild type (WT) littermates. Kainate also substantially enhances seizure-associated gamma oscillatory activity in juvenile mZnR/GPR39 KO hippocampal slices, a phenomenon that can be reproduced in WT tissue by extracellular Zn2+ chelation. Importantly, kainate-induced synaptic Zn2+ release enhances surface expression and transport activity of KCC2 in WT, but not mZnR/GPR39 KO hippocampal neurons. Kainate-dependent upregulation of KCC2 requires mZnR/GPR39 activation of the Gαq/phospholipase C/extracellular regulated kinase (ERK1/2) signaling cascade. We suggest that mZnR/GPR39-dependent upregulation of KCC2 activity provides homeostatic adaptation to an excitotoxic stimulus by increasing inhibition. As such, mZnR/GPR39 may provide a novel pharmacological target for dampening epileptic seizure activity. PMID:25562657

  16. Stroke-like episodes, peri-episodic seizures, and MELAS mutations.

    PubMed

    Finsterer, Josef; Wakil, Salma Majid

    2016-11-01

    Stroke-like episodes (SLEs) are a hallmark of various mitochondrial disorders, in particular MELAS syndrome. SLEs manifest with vasogenic oedema (DWI and ADC hyperintensity) or partial cytotoxic oedema (DWI hyperintensity, ADC hypointensity) in the acute and subacute stage, and with gyriform T1-hyperintensity (cortical necrosis) in the chronic stage. SLEs must be clearly distinguished from ischaemic stroke, since management of these two entities is different. SLEs may go along with or without seizures or epileptiform discharges on EEG. However, in MELAS syndrome seizures may also occur in the absence of SLEs. Focal and generalised seizures have been reported but it is currently unknown if the one or the other prevail. SLEs with and without seizures may respond to NO-precursors l-arginine, succinate, or citrulline. As a supportive measure a ketogenic diet should be initiated. Seizures prior to or during a SLE or paroxysmal EEG-activity during a SLE should be initially treated with antiepileptic drugs (AEDs) with low mitochondrion-toxicity. Only in case these AEDs are ineffective, AEDs with higher mitochondrion-toxicity should be added. All patients with SLEs need to have an EEG recorded irrespective if they have manifesting seizures or not. There are no mtDNA or nDNA mutations which predispose for SLEs with seizures. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  17. Clinical characteristics of patients seizure following the 2016 Kumamoto earthquake.

    PubMed

    Inatomi, Yuichiro; Nakajima, Makoto; Yonehara, Toshiro; Ando, Yukio

    2017-06-01

    To investigate the clinical characteristics of patients with seizure following the 2016 Kumamoto earthquake. We retrospectively studied patients with seizure admitted to our hospital for 12weeks following the earthquake. We compared the clinical backgrounds and characteristics of the patients: before (the same period from the previous 3years) and after the earthquake; and the early (first 2weeks) and late (subsequent 10weeks) phases. A total of 60 patients with seizure were admitted to the emergency room after the earthquake, and 175 (58.3/year) patients were admitted before the earthquake. Of them, 35 patients with seizure were hospitalized in the Department of Neurology after the earthquake, and 96 (32/year) patients were hospitalized before the earthquake. In patients after the earthquake, males and non-cerebrovascular diseases as an epileptogenic disease were seen more frequently than before the earthquake. During the early phase after the earthquake, female, first-attack, and non-focal-type patients were seen more frequently than during the late phase after the earthquake. These characteristics of patients with seizure during the early phase after the earthquake suggest that many patients had non-epileptic seizures. To prevent seizures following earthquakes, mental stress and physical status of evacuees must be assessed. Copyright © 2017. Published by Elsevier Ltd.

  18. Excitatory Effects of Parvalbumin-Expressing Interneurons Maintain Hippocampal Epileptiform Activity via Synchronous Afterdischarges

    PubMed Central

    Ellender, Tommas J.; Raimondo, Joseph V.; Irkle, Agnese; Lamsa, Karri P.

    2014-01-01

    Epileptic seizures are characterized by periods of hypersynchronous, hyperexcitability within brain networks. Most seizures involve two stages: an initial tonic phase, followed by a longer clonic phase that is characterized by rhythmic bouts of synchronized network activity called afterdischarges (ADs). Here we investigate the cellular and network mechanisms underlying hippocampal ADs in an effort to understand how they maintain seizure activity. Using in vitro hippocampal slice models from rats and mice, we performed electrophysiological recordings from CA3 pyramidal neurons to monitor network activity and changes in GABAergic signaling during epileptiform activity. First, we show that the highest synchrony occurs during clonic ADs, consistent with the idea that specific circuit dynamics underlie this phase of the epileptiform activity. We then show that ADs require intact GABAergic synaptic transmission, which becomes excitatory as a result of a transient collapse in the chloride (Cl−) reversal potential. The depolarizing effects of GABA are strongest at the soma of pyramidal neurons, which implicates somatic-targeting interneurons in AD activity. To test this, we used optogenetic techniques to selectively control the activity of somatic-targeting parvalbumin-expressing (PV+) interneurons. Channelrhodopsin-2-mediated activation of PV+ interneurons during the clonic phase generated excitatory GABAergic responses in pyramidal neurons, which were sufficient to elicit and entrain synchronous AD activity across the network. Finally, archaerhodopsin-mediated selective silencing of PV+ interneurons reduced the occurrence of ADs during the clonic phase. Therefore, we propose that activity-dependent Cl− accumulation subverts the actions of PV+ interneurons to perpetuate rather than terminate pathological network hyperexcitability during the clonic phase of seizures. PMID:25392490

  19. Seizure frequency correlates with loss of dentate gyrus GABAergic neurons in a mouse model of temporal lobe epilepsy

    PubMed Central

    Buckmaster, Paul S.; Abrams, Emily; Wen, Xiling

    2018-01-01

    Epilepsy occurs in one of 26 people. Temporal lobe epilepsy is common and can be difficult to treat effectively. It can develop after brain injuries that damage the hippocampus. Multiple pathophysiological mechanisms involving the hippocampal dentate gyrus have been proposed. This study evaluated a mouse model of temporal lobe epilepsy to test which pathological changes in the dentate gyrus correlate with seizure frequency and help prioritize potential mechanisms for further study. FVB mice (n = 127) that had experienced status epilepticus after systemic treatment with pilocarpine 31–61 days earlier were video-monitored for spontaneous, convulsive seizures 9 hr/day every day for 24–36 days. Over 4,060 seizures were observed. Seizure frequency ranged from an average of one every 3.6 days to one every 2.1 hr. Hippocampal sections were processed for Nissl stain, Prox1-immunocytochemistry, GluR2-immunocytochemistry, Timm stain, glial fibrillary acidic protein-immunocytochemistry, glutamic acid decarboxylase in situ hybridization, and parvalbumin-immunocytochemistry. Stereological methods were used to measure hilar ectopic granule cells, mossy cells, mossy fiber sprouting, astrogliosis, and GABAergic interneurons. Seizure frequency was not significantly correlated with the generation of hilar ectopic granule cells, the number of mossy cells, the extent of mossy fiber sprouting, the extent of astrogliosis, or the number of GABAergic interneurons in the molecular layer or hilus. Seizure frequency significantly correlated with the loss of GABAergic interneurons in or adjacent to the granule cell layer, but not with the loss of parvalbumin-positive interneurons. These findings prioritize the loss of granule cell layer interneurons for further testing as a potential cause of temporal lobe epilepsy. PMID:28425097

  20. Seizure frequency correlates with loss of dentate gyrus GABAergic neurons in a mouse model of temporal lobe epilepsy.

    PubMed

    Buckmaster, Paul S; Abrams, Emily; Wen, Xiling

    2017-08-01

    Epilepsy occurs in one of 26 people. Temporal lobe epilepsy is common and can be difficult to treat effectively. It can develop after brain injuries that damage the hippocampus. Multiple pathophysiological mechanisms involving the hippocampal dentate gyrus have been proposed. This study evaluated a mouse model of temporal lobe epilepsy to test which pathological changes in the dentate gyrus correlate with seizure frequency and help prioritize potential mechanisms for further study. FVB mice (n = 127) that had experienced status epilepticus after systemic treatment with pilocarpine 31-61 days earlier were video-monitored for spontaneous, convulsive seizures 9 hr/day every day for 24-36 days. Over 4,060 seizures were observed. Seizure frequency ranged from an average of one every 3.6 days to one every 2.1 hr. Hippocampal sections were processed for Nissl stain, Prox1-immunocytochemistry, GluR2-immunocytochemistry, Timm stain, glial fibrillary acidic protein-immunocytochemistry, glutamic acid decarboxylase in situ hybridization, and parvalbumin-immunocytochemistry. Stereological methods were used to measure hilar ectopic granule cells, mossy cells, mossy fiber sprouting, astrogliosis, and GABAergic interneurons. Seizure frequency was not significantly correlated with the generation of hilar ectopic granule cells, the number of mossy cells, the extent of mossy fiber sprouting, the extent of astrogliosis, or the number of GABAergic interneurons in the molecular layer or hilus. Seizure frequency significantly correlated with the loss of GABAergic interneurons in or adjacent to the granule cell layer, but not with the loss of parvalbumin-positive interneurons. These findings prioritize the loss of granule cell layer interneurons for further testing as a potential cause of temporal lobe epilepsy. © 2017 Wiley Periodicals, Inc.

  1. Impaired recruitment of seizure-generated neurons into functional memory networks of the adult dentate gyrus following long-term amygdala kindling.

    PubMed

    Fournier, Neil M; Botterill, Justin J; Marks, Wendie N; Guskjolen, Axel J; Kalynchuk, Lisa E

    2013-06-01

    Epileptic seizures increase the birth of new neurons in the adult hippocampus. Although the consequences of aberrant neurogenesis on behavior are not fully understood, one hypothesis is that seizure-generated neurons might form faulty circuits that disrupt hippocampal functions, such as learning and memory. In the present study, we employed long-term amygdala kindling (i.e., rats receive 99-electrical stimulations) to examine the effect of repeated seizures on hippocampal neurogenesis and behavior. We labeled seizure-generated cells with the proliferation marker BrdU after 30-stimulations and continued kindling for an additional 4weeks to allow newborn neurons to mature under conditions of repeated seizures. After kindling was complete, rats were tested in a trace fear conditioning task and sacrificed 2h later to examine if 4-week old newborn cells were recruited into circuits involved in the retrieval of emotional memory. Compared to non-kindled controls, long-term kindled rats showed significant impairments in fear memory reflected in a decrease in conditioned freezing to both tone and contextual cues during testing. Moreover, long-term kindling also prevented the activation of 4-week old newborn cells in response to fear memory retrieval. These results indicate that the presence of seizure activity during cell maturation impedes the ability of new neurons to integrate properly into circuits important in memory formation. Together, our findings suggest that aberrant seizure-induced neurogenesis might contribute to the development of learning impairments in chronic epilepsy and raise the possibility that targeting the reduced activation of adult born neurons could represent a beneficial strategy to reverse cognitive deficits in some epileptic patients. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. CONTROVERSIES IN EPILEPSY – DEBATES HELD DURING THE FOURTH INTERNATIONAL WORKSHOP ON SEIZURE PREDICTION

    PubMed Central

    Frei, Mark G.; Zaveri, Hitten P.; Arthurs, Susan; Bergey, Gregory K.; Jouny, Christophe; Lehnertz, Klaus; Gotman, Jean; Osorio, Ivan; Netoff, Theoden I.; Freeman, Walter J.; Jefferys, John; Worrell, Gregory; Le Van Quyen, Michel; Schiff, Steven J.; Mormann, Florian

    2010-01-01

    Debates on 6 controversial topics were held during the Fourth International Workshop on Seizure Prediction (IWSP4) convened in Kansas City (July 4–7, 2009). The topics were 1) Ictogenesis: focus vs. network? 2) Spikes and seizures: step-relatives or siblings? 3) Ictogenesis: a result of hyposynchrony? 4) Can focal seizures be caused by excessive inhibition? 5) Do high-frequency oscillations (HFOs) provide relevant independent information? and 6) Phase synchronization – is it worthwhile as measured? This manuscript, written by the IWSP4 organizing committee and the debaters, summarizes the arguments presented during the debates. PMID:20708976

  3. Interleukin-1 Receptor in Seizure Susceptibility after Traumatic Injury to the Pediatric Brain

    PubMed Central

    O'Brien, Terence J.; Gimlin, Kayleen; Wright, David K.; Kim, Shi Eun; Casillas-Espinosa, Pablo M.; Webster, Kyria M.; Petrou, Steven; Noble-Haeusslein, Linda J.

    2017-01-01

    Epilepsy after pediatric traumatic brain injury (TBI) is associated with poor quality of life. This study aimed to characterize post-traumatic epilepsy in a mouse model of pediatric brain injury, and to evaluate the role of interleukin-1 (IL-1) signaling as a target for pharmacological intervention. Male mice received a controlled cortical impact or sham surgery at postnatal day 21, approximating a toddler-aged child. Mice were treated acutely with an IL-1 receptor antagonist (IL-1Ra; 100 mg/kg, s.c.) or vehicle. Spontaneous and evoked seizures were evaluated from video-EEG recordings. Behavioral assays tested for functional outcomes, postmortem analyses assessed neuropathology, and brain atrophy was detected by ex vivo magnetic resonance imaging. At 2 weeks and 3 months post-injury, TBI mice showed an elevated seizure response to the convulsant pentylenetetrazol compared with sham mice, associated with abnormal hippocampal mossy fiber sprouting. A robust increase in IL-1β and IL-1 receptor were detected after TBI. IL-1Ra treatment reduced seizure susceptibility 2 weeks after TBI compared with vehicle, and a reduction in hippocampal astrogliosis. In a chronic study, IL-1Ra-TBI mice showed improved spatial memory at 4 months post-injury. At 5 months, most TBI mice exhibited spontaneous seizures during a 7 d video-EEG recording period. At 6 months, IL-1Ra-TBI mice had fewer evoked seizures compared with vehicle controls, coinciding with greater preservation of cortical tissue. Findings demonstrate this model's utility to delineate mechanisms underlying epileptogenesis after pediatric brain injury, and provide evidence of IL-1 signaling as a mediator of post-traumatic astrogliosis and seizure susceptibility. SIGNIFICANCE STATEMENT Epilepsy is a common cause of morbidity after traumatic brain injury in early childhood. However, a limited understanding of how epilepsy develops, particularly in the immature brain, likely contributes to the lack of efficacious treatments

  4. Dynamic Imaging of Coherent Sources Reveals Different Network Connectivity Underlying the Generation and Perpetuation of Epileptic Seizures

    PubMed Central

    Anwar, Abdul Rauf; Deuschl, Günther; Stephani, Ulrich; Raethjen, Jan; Siniatchkin, Michael

    2013-01-01

    The concept of focal epilepsies includes a seizure origin in brain regions with hyper synchronous activity (epileptogenic zone and seizure onset zone) and a complex epileptic network of different brain areas involved in the generation, propagation, and modulation of seizures. The purpose of this work was to study functional and effective connectivity between regions involved in networks of epileptic seizures. The beginning and middle part of focal seizures from ictal surface EEG data were analyzed using dynamic imaging of coherent sources (DICS), an inverse solution in the frequency domain which describes neuronal networks and coherences of oscillatory brain activities. The information flow (effective connectivity) between coherent sources was investigated using the renormalized partial directed coherence (RPDC) method. In 8/11 patients, the first and second source of epileptic activity as found by DICS were concordant with the operative resection site; these patients became seizure free after epilepsy surgery. In the remaining 3 patients, the results of DICS / RPDC calculations and the resection site were discordant; these patients had a poorer post-operative outcome. The first sources as found by DICS were located predominantly in cortical structures; subsequent sources included some subcortical structures: thalamus, Nucl. Subthalamicus and cerebellum. DICS seems to be a powerful tool to define the seizure onset zone and the epileptic networks involved. Seizure generation seems to be related to the propagation of epileptic activity from the primary source in the seizure onset zone, and maintenance of seizures is attributed to the perpetuation of epileptic activity between nodes in the epileptic network. Despite of these promising results, this proof of principle study needs further confirmation prior to the use of the described methods in the clinical praxis. PMID:24194931

  5. Sensor integration of multiple tripolar concentric ring electrodes improves pentylenetetrazole-induced seizure onset detection in rats.

    PubMed

    Makeyev, Oleksandr; Ding, Quan; Kay, Steven M; Besio, Walter G

    2012-01-01

    As epilepsy affects approximately one percent of the world population, electrical stimulation of the brain has recently shown potential for additive seizure control therapy. Previously, we applied noninvasive transcranial focal stimulation via tripolar concentric ring electrodes on the scalp of rats after inducing seizures with pentylenetetrazole. We developed a system to detect seizures and automatically trigger the stimulation and evaluated the system on the electrographic activity from rats. In this preliminary study we propose and validate a novel seizure onset detection algorithm based on exponentially embedded family. Unlike the previously proposed approach it integrates the data from multiple electrodes allowing an improvement of the detector performance.

  6. Hippocampal low-frequency stimulation inhibits afterdischarge and increases GABA (A) receptor expression in amygdala-kindled pharmacoresistant epileptic rats.

    PubMed

    Wu, Guofeng; Wang, Likun; Hong, Zhen; Ren, Siying; Zhou, Feng

    2017-08-01

    The purpose of the present study was to observe the effects of hippocampal low-frequency stimulation (Hip-LFS) on amygdala afterdischarge and GABA (A) receptor expression in pharmacoresistant epileptic (PRE) rats. A total of 110 healthy adult male Wistar rats were used to generate a model of epilepsy by chronic stimulation of the amygdala. Sixteen PRE rats were selected from 70 amygdala-kindled rats by testing their response to Phenytoin and Phenobarbital, and they were randomly assigned to a pharmacoresistant stimulation group (PRS group, 8 rats) or a pharmacoresistant control group (PRC group, 8 rats). A stimulation electrode was implanted into the hippocampus of all of the rats. Hip-LFS was administered twice per day in the PRS group for two weeks. Simultaneously, amygdala stimulus-induced seizures and afterdischarge were recorded. After the hippocampal stimulation was terminated, the brain tissues were obtained to determine the GABA (A) receptors by a method of immumohistochemistry and a real-time polymerase chain reaction. The stages and duration of the amygdala stimulus-induced epileptic seizures were decreased in the PRS group. The afterdischarge threshold was increased and the duration as well as the afterdischarge frequency was decreased. Simultaneously, the GABA (A) expression was significantly increased in the PRS group. Hip-LFS may inhibit amygdala stimulus-induced epileptic seizures and up-regulate GABA (A) receptor expression in PRE rats. The antiepileptic effects of hippocampal stimulation may be partly achieved by increasing the GABA (A) receptor.

  7. 3 Tesla MRI-negative focal epilepsies: Presurgical evaluation, postoperative outcome and predictive factors.

    PubMed

    Kogias, Evangelos; Klingler, Jan-Helge; Urbach, Horst; Scheiwe, Christian; Schmeiser, Barbara; Doostkam, Soroush; Zentner, Josef; Altenmüller, Dirk-Matthias

    2017-12-01

    To investigate presurgical diagnostic modalities, clinical and seizure outcome as well as predictive factors after resective epilepsy surgery in 3 Tesla MRI-negative focal epilepsies. This retrospective study comprises 26 patients (11 males/15 females, mean age 34±12years, range 13-50 years) with 3 Tesla MRI-negative focal epilepsies who underwent resective epilepsy surgery. Non-invasive and invasive presurgical diagnostic modalities, type and localization of resection, clinical and epileptological outcome with a minimum follow-up of 1year (range 1-11 years, mean 2.5±2.3years) after surgery as well as outcome predictors were evaluated. All patients underwent invasive video-EEG monitoring after implantation of intracerebral depth and/or subdural electrodes. Ten patients received temporal and 16 extratemporal or multilobar (n=4) resections. There was no perioperative death or permanent morbidity. Overall, 12 of 26 patients (46%) were completely seizure-free (Engel IA) and 65% had a favorable outcome (Engel I-II). In particular, seizure-free ratio was 40% in the temporal and 50% in the extratemporal group. In the temporal group, long duration of epilepsy correlated with poor seizure outcome, whereas congruent unilateral FDG-PET hypometabolism correlated with a favorable outcome. In almost two thirds of temporal and extratemporal epilepsies defined as "non-lesional" by 3 Tesla MRI criteria, a favorable postoperative seizure outcome (Engel I-II) can be achieved with accurate multimodal presurgical evaluation including intracranial EEG recordings. In the temporal group, most favorable results were obtained when FDG-PET displayed congruent unilateral hypometabolism. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Targeting deficiencies in mitochondrial respiratory complex I and functional uncoupling exerts anti-seizure effects in a genetic model of temporal lobe epilepsy and in a model of acute temporal lobe seizures.

    PubMed

    Simeone, Kristina A; Matthews, Stephanie A; Samson, Kaeli K; Simeone, Timothy A

    2014-01-01

    Mitochondria actively participate in neurotransmission by providing energy (ATP) and maintaining normative concentrations of reactive oxygen species (ROS) in both presynaptic and postsynaptic elements. In human and animal epilepsies, ATP-producing respiratory rates driven by mitochondrial respiratory complex (MRC) I are reduced, antioxidant systems are attenuated and oxidative damage is increased. We report that MRCI-driven respiration and functional uncoupling (an inducible antioxidant mechanism) are reduced and levels of H2O2 are elevated in mitochondria isolated from KO mice. Experimental impairment of MRCI in WT hippocampal slices via rotenone reduces paired-pulse ratios (PPRs) at mossy fiber-CA3 synapses (resembling KO PPRs), and exacerbates seizure-like events in vitro. Daily treatment with AATP [a combination therapy composed of ascorbic acid (AA), alpha-tocopherol (T), sodium pyruvate (P) designed to synergistically target mitochondrial impairments] improved mitochondrial functions, mossy fiber PPRs, and reduced seizure burden index (SBI) scores and seizure incidence in KO mice. AATP pretreatment reduced severity of KA-induced seizures resulting in 100% protection from the severe tonic-clonic seizures in WT mice. These data suggest that restoration of bioenergetic homeostasis in the brain may represent a viable anti-seizure target for temporal lobe epilepsy. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Comparison between febrile and afebrile seizures associated with mild rotavirus gastroenteritis.

    PubMed

    Kang, Ben; Kim, Dong Hyun; Hong, Young Jin; Son, Byong Kwan; Kim, Dong Wook; Kwon, Young Se

    2013-09-01

    We aimed on identifying the differences of febrile and afebrile seizures associated with mild rotavirus gastroenteritis (RVGE) in the pediatric population. Medical charts of pediatric patients who had been admitted between July 1999 and June 2011 due to RVGE were retrospectively reviewed. Subjects were ultimately divided into three groups; 'no seizure' (NS: patients without seizure), 'febrile seizure' (FS: patients with fever during seizure), 'afebrile seizure' (AFS: patients without fever during seizure). Comparisons between groups were carried out on demographic and clinical characteristics, laboratory test results, electroencephalogram findings, brain magnetic resonance imaging findings, antiepileptic treatment, and prognosis. Among the 755 subjects who had been admitted due to mild rotavirus enteritis, 696 (90.3%) did not have any seizures, 17 (2.2%) had febrile seizures, 42 (5.5%) had afebrile seizures. The duration of gastrointestinal symptoms before the onset of seizures were significantly shorter in the FS group compared to the AFS group (1.3±0.8 vs. 2.8±1.0 days; p<0.0001). A single seizure attack was significantly higher in the AFS group (3.0±1.6 vs. 1.7±1.0 episodes; p=0.0003), and the frequency of seizures that were of focal type with or without secondary generalization were significantly higher in the AFS group (33.3% vs. 6.0%; p=0.0139). All patients among the FS and AFS group had not received further antiepileptic treatment after discharge, and none developed epilepsy during follow up period. Despite some differences in seizure characteristics, both febrile and afebrile seizures associated with mild RVGE were mostly benign with a favorable prognosis. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  10. Seizure semiology: an important clinical clue to the diagnosis of autoimmune epilepsy.

    PubMed

    Lv, Rui-Juan; Ren, Hai-Tao; Guan, Hong-Zhi; Cui, Tao; Shao, Xiao-Qiu

    2018-02-01

    The purpose of this study is to analyze the seizure semiologic characteristics of patients with autoimmune epilepsy (AE) and describe the investigation characteristics of AE using a larger sample size. This observational retrospective case series study was conducted from a tertiary epilepsy center between May 2014 and March 2017. Cases of new-onset seizures were selected based on laboratory evidence of autoimmunity. At the same time, typical mesial temporal lobe epilepsy (MTLE) patients with hippocampal sclerosis (HS) were recruited as the control group from the subjects who underwent presurgical evaluation during the same period. A total of 61 patients with AE were identified. Specific autoimmune antibodies were detected in 39 patients (63.93%), including anti-VGKC in 23 patients (37.70%), anti-NMDA-R in 9 patients (14.75%), anti-GABA B -R in 6 patients (9.84%), and anti-amphiphysin in 1 patient (1.64%). Regarding the seizure semiology, no significant differences were noted between AE patients with autoantibody and patients with suspected AE without antibody. Compared to typical MTLE patients with HS, both AE patients with autoantibody and patients with suspected AE without antibody had the same seizure semiologic characteristics, including more frequent SPS or CPS, shorter seizure duration, rare postictal confusion, and common sleeping SGTC seizures. This study highlights important seizure semiologic characteristics of AE. Patients with autoimmune epilepsy had special seizure semiologic characteristics. For patients with autoimmune epilepsy presenting with new-onset seizures in isolation or with a seizure-predominant neurological disorder, the special seizure semiologic characteristics may remind us to test neuronal nuclear/cytoplasmic antibodies early and initiate immunomodulatory therapies as soon as possible. Furthermore, the absence of neural-specific autoantibodies does not rule out AE.

  11. Innate but not Adaptive Immune Responses Contribute to Behavioral Seizures Following Viral Infection

    PubMed Central

    Kirkman, Nikki J.; Libbey, Jane E.; Wilcox, Karen S.; White, H. Steve; Fujinami, Robert S.

    2011-01-01

    SUMMARY Purpose To examine the role of innate immunity in a novel viral infection-induced seizure model. Methods C57BL/6 mice, mouse strains deficient in interleukin (IL)-1RI, IL-6, tumor necrosis factor (TNF)-RI, or myeloid differentiation primary response gene 88 (MyD88), or transgenic mice (OT-I) were infected with Theiler’s murine encephalomyelitis virus (TMEV) or mock-infected. Mice were followed for acute seizures. Tissues were examined for neuron loss, the presence of virus (viral RNA and antigen), perivascular cuffs, macrophages/microglia and gliosis, and mRNA expression of IL-1, TNF-α and IL-6. Results IL-1 does not play a major role in seizures as IL-1RI and MyD88 deficient mice displayed a comparable seizure frequency relative to controls. In contrast, TNF-α and IL-6 appear to be important in the development of seizures as only 10% and 15% of TNF-RI and IL-6 deficient mice showed signs of seizure activity, respectively. TNF-α and IL-6 mRNA levels also increased in mice with seizures. Inflammation (perivascular cuffs, macrophages/microglia and gliosis) was greater in mice with seizures. OT-I mice (virus persists) had a seizure rate that was comparable to controls (no viral persistence) thereby discounting a role for TMEV-specific T–cells in seizures. Discussion We have implicated the innate immune response to viral infection, specifically TNF-α and IL-6, and concomitant inflammatory changes in the brain as contributing to the development of acute seizures. This model is a potential infection-driven model of mesial temporal lobe epilepsy with hippocampal sclerosis. PMID:19845729

  12. Epileptic Networks in Focal Cortical Dysplasia Revealed Using Electroencephalography–Functional Magnetic Resonance Imaging

    PubMed Central

    Thornton, Rachel; Vulliemoz, Serge; Rodionov, Roman; Carmichael, David W; Chaudhary, Umair J; Diehl, Beate; Laufs, Helmut; Vollmar, Christian; McEvoy, Andrew W; Walker, Matthew C; Bartolomei, Fabrice; Guye, Maxime; Chauvel, Patrick; Duncan, John S; Lemieux, Louis

    2011-01-01

    Objective Surgical treatment of focal epilepsy in patients with focal cortical dysplasia (FCD) is most successful if all epileptogenic tissue is resected. This may not be evident on structural magnetic resonance imaging (MRI), so intracranial electroencephalography (icEEG) is needed to delineate the seizure onset zone (SOZ). EEG-functional MRI (fMRI) can reveal interictal discharge (IED)-related hemodynamic changes in the irritative zone (IZ). We assessed the value of EEG-fMRI in patients with FCD-associated focal epilepsy by examining the relationship between IED-related hemodynamic changes, icEEG findings, and postoperative outcome. Methods Twenty-three patients with FCD-associated focal epilepsy undergoing presurgical evaluation including icEEG underwent simultaneous EEG-fMRI at 3T. IED-related hemodynamic changes were modeled, and results were overlaid on coregistered T1-weighted MRI scans fused with computed tomography scans showing the intracranial electrodes. IED-related hemodynamic changes were compared with the SOZ on icEEG and postoperative outcome at 1 year. Results Twelve of 23 patients had IEDs during recording, and 11 of 12 had significant IED-related hemodynamic changes. The fMRI results were concordant with the SOZ in 5 of 11 patients, all of whom had a solitary SOZ on icEEG. Four of 5 had >50% reduction in seizure frequency following resective surgery. The remaining 6 of 11 patients had widespread or discordant regions of IED-related fMRI signal change. Five of 6 had either a poor surgical outcome (<50% reduction in seizure frequency) or widespread SOZ precluding surgery. Interpretation Comparison of EEG-fMRI with icEEG suggests that EEG-fMRI may provide useful additional information about the SOZ in FCD. Widely distributed discordant regions of IED-related hemodynamic change appear to be associated with a widespread SOZ and poor postsurgical outcome. ANN NEUROL 2011 PMID:22162063

  13. Trans-Modulation of the Somatostatin Type 2A Receptor Trafficking by Insulin-Regulated Aminopeptidase Decreases Limbic Seizures.

    PubMed

    De Bundel, Dimitri; Fafouri, Assia; Csaba, Zsolt; Loyens, Ellen; Lebon, Sophie; El Ghouzzi, Vincent; Peineau, Stéphane; Vodjdani, Guilan; Kiagiadaki, Foteini; Aourz, Najat; Coppens, Jessica; Walrave, Laura; Portelli, Jeanelle; Vanderheyden, Patrick; Chai, Siew Yeen; Thermos, Kyriaki; Bernard, Véronique; Collingridge, Graham; Auvin, Stéphane; Gressens, Pierre; Smolders, Ilse; Dournaud, Pascal

    2015-08-26

    Within the hippocampus, the major somatostatin (SRIF) receptor subtype, the sst2A receptor, is localized at postsynaptic sites of the principal neurons where it modulates neuronal activity. Following agonist exposure, this receptor rapidly internalizes and recycles slowly through the trans-Golgi network. In epilepsy, a high and chronic release of somatostatin occurs, which provokes, in both rat and human tissue, a decrease in the density of this inhibitory receptor at the cell surface. The insulin-regulated aminopeptidase (IRAP) is involved in vesicular trafficking and shares common regional distribution with the sst2A receptor. In addition, IRAP ligands display anticonvulsive properties. We therefore sought to assess by in vitro and in vivo experiments in hippocampal rat tissue whether IRAP ligands could regulate the trafficking of the sst2A receptor and, consequently, modulate limbic seizures. Using pharmacological and cell biological approaches, we demonstrate that IRAP ligands accelerate the recycling of the sst2A receptor that has internalized in neurons in vitro or in vivo. Most importantly, because IRAP ligands increase the density of this inhibitory receptor at the plasma membrane, they also potentiate the neuropeptide SRIF inhibitory effects on seizure activity. Our results further demonstrate that IRAP is a therapeutic target for the treatment of limbic seizures and possibly for other neurological conditions in which downregulation of G-protein-coupled receptors occurs. The somatostatin type 2A receptor (sst2A) is localized on principal hippocampal neurons and displays anticonvulsant properties. Following agonist exposure, however, this receptor rapidly internalizes and recycles slowly. The insulin-regulated aminopeptidase (IRAP) is involved in vesicular trafficking and shares common regional distribution with the sst2A receptor. We therefore assessed by in vitro and in vivo experiments whether IRAP could regulate the trafficking of this receptor. We

  14. Stereotyped high-frequency oscillations discriminate seizure onset zones and critical functional cortex in focal epilepsy.

    PubMed

    Liu, Su; Gurses, Candan; Sha, Zhiyi; Quach, Michael M; Sencer, Altay; Bebek, Nerses; Curry, Daniel J; Prabhu, Sujit; Tummala, Sudhakar; Henry, Thomas R; Ince, Nuri F

    2018-01-30

    High-frequency oscillations in local field potentials recorded with intracranial EEG are putative biomarkers of seizure onset zones in epileptic brain. However, localized 80-500 Hz oscillations can also be recorded from normal and non-epileptic cerebral structures. When defined only by rate or frequency, physiological high-frequency oscillations are indistinguishable from pathological ones, which limit their application in epilepsy presurgical planning. We hypothesized that pathological high-frequency oscillations occur in a repetitive fashion with a similar waveform morphology that specifically indicates seizure onset zones. We investigated the waveform patterns of automatically detected high-frequency oscillations in 13 epilepsy patients and five control subjects, with an average of 73 subdural and intracerebral electrodes recorded per patient. The repetitive oscillatory waveforms were identified by using a pipeline of unsupervised machine learning techniques and were then correlated with independently clinician-defined seizure onset zones. Consistently in all patients, the stereotypical high-frequency oscillations with the highest degree of waveform similarity were localized within the seizure onset zones only, whereas the channels generating high-frequency oscillations embedded in random waveforms were found in the functional regions independent from the epileptogenic locations. The repetitive waveform pattern was more evident in fast ripples compared to ripples, suggesting a potential association between waveform repetition and the underlying pathological network. Our findings provided a new tool for the interpretation of pathological high-frequency oscillations that can be efficiently applied to distinguish seizure onset zones from functionally important sites, which is a critical step towards the translation of these signature events into valid clinical biomarkers.awx374media15721572971001. © The Author(s) (2018). Published by Oxford University Press on

  15. Subacute Fluoxetine Reduces Signs of Hippocampal Damage Induced by a Single Convulsant Dose of 4-Aminopyridine in Rats.

    PubMed

    Shiha, Ahmed A; de la Rosa, Rubén Fernández; Delgado, Mercedes; Pozo, Miguel A; García-García, Luis

    2017-01-01

    Epilepsy is a central disorder associated with neuronal damage and brain hypometabolism. It has been reported that antidepressant drugs show anticonvulsant and neuroprotective effects in different animal models of seizures and epilepsy. The purpose of this study was to investigate the eventual short-term brain impairment induced by a single low convulsant dose of the potassium channel blocker 4-aminopyridine (4-AP) and the eventual neuroprotective effects exerted by fluoxetine, a prototypical selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor (SSRI). In vivo 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET) and several histological assessments were carried out in adult male rats after i.p. administration of 3 mg/kg 4-AP for evaluating eventual brain metabolism impairment and signs of hippocampal damage. We also evaluated the effects of a short-term fluoxetine treatment (10 mg/kg, i.p. for 7 days) in this seizure model. [18F]FDG PET analysis revealed no changes in the regional brain metabolism on day 3 after 4-AP injection. The histological assessments revealed signs of damage in the hippocampus, a brain area usually affected by seizures. Thus, reactive gliosis and a significant increase in the expression of caspase-9 were found in the aforementioned brain area. By contrast, we observed no signs of neurodegeneration or neuronal death. Regarding the effects of fluoxetine, this SSRI showed beneficial neurologic effects, since it significantly increased the seizure latency time and reduced the abovementioned 4-AP-induced hippocampal damage markers. Overall, our results point to SSRIs and eventually endogenous 5-HT as neuroprotective agents against convulsant-induced hippocampal damage. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Which Brain Regions are Important for Seizure Dynamics in Epileptic Networks? Influence of Link Identification and EEG Recording Montage on Node Centralities.

    PubMed

    Geier, Christian; Lehnertz, Klaus

    2017-02-01

    Nodes in large-scale epileptic networks that are crucial for seizure facilitation and termination can be regarded as potential targets for individualized focal therapies. Graph-theoretical approaches based on centrality concepts can help to identify such important nodes, however, they may be influenced by the way networks are derived from empirical data. Here we investigate evolving functional epileptic brain networks during 82 focal seizures with different anatomical onset locations that we derive from multichannel intracranial electroencephalographic recordings from 51 patients. We demonstrate how the various methodological steps (from the recording montage via node and link inference to the assessment of node centralities) affect importance estimation and discuss their impact on the interpretability of findings in the context of pathophysiological aspects of seizure dynamics.

  17. Increase in gray matter volume and white matter fractional anisotropy in the motor pathways of patients with secondarily generalized neocortical seizures.

    PubMed

    Hsin, Yue-Loong; Harnod, Tomor; Chang, Cheng-Siu; Peng, Syu-Jyun

    2017-11-01

    Convulsive motor activity is a clinical manifestation of secondarily generalized seizures evolving from different focal regions. The way in which the motor seizures present themselves is not very different from most of the generalized seizures in and between epilepsy patients. This might point towards the involvement of motor-related cortices and corticospinal pathway for wide spread propagation of epileptic activity. Our aim was to identify changes in the cerebral structures and to correlate clinical variables with structural changes particularly in the motor-related cortices and pathway of patients with generalized convulsions from different seizure foci. Sixteen patients with focal onset and secondarily generalized seizures were included, along with sixteen healthy volunteers. Structural differences were analysed by measuring grey matter (GM) volume and thickness via T1-weighted MRI, and white matter (WM) fractional anisotropy (FA) via diffusion tensor imaging. GM and WM microstructural properties were compared between patients and controls by voxel- and surface- based analyses. Next, morphometric findings were correlated with seizure severity and disease duration to identify the pathologic process. In addition to widely reduced GM and WM properties, increased GM volume in the bilateral precentral gyri and paracentral lobules, and elevated regional FA in the bilateral corticospinal tracts adjacent to these motor -related GM were observed in patients and with higher statistical difference in the sub-patient group with drug-resistance. The increment of GM volume and WM FA in the motor pathway positively correlated with severity and duration of epilepsy. The demonstrated microstructural changes of motor pathways imply a plastic process of motor networks in the patients with frequent generalization of focal seizures. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  18. Seizure Semiology: Its Value and Limitations in Localizing the Epileptogenic Zone

    PubMed Central

    Lüders, Hans O.

    2012-01-01

    Epilepsy surgery has become an important treatment option in patients with medically refractory epilepsy. The ability to precisely localize the epileptogenic zone is crucial for surgical success. The tools available for localization of the epileptogenic zone are limited. Seizure semiology is a simple and cost effective tool that allows localization of the symptomatogenic zone which either overlaps or is in close proximity of the epileptogenic zone. This becomes particularly important in cases of MRI negative focal epilepsy. The ability to video record seizures made it possible to discover new localizing signs and quantify the sensitivity and specificity of others. Ideally the signs used for localization should fulfill these criteria; 1) Easy to identify and have a high inter-rater reliability, 2) It has to be the first or one of the earlier components of the seizure in order to have localizing value. Later symptoms or signs are more likely to be due to ictal spread and may have only a lateralizing value. 3) The symptomatogenic zone corresponding to the recorded ictal symptom has to be clearly defined and well documented. Reproducibility of the initial ictal symptoms with cortical stimulation identifies the corresponding symptomatogenic zone. Unfortunately, however, not all ictal symptoms can be reproduced by focal cortical stimulation. Therefore, the problem the clinician faces is trying to deduce the epileptogenic zone from the seizure semiology. The semiological classification system is particularly useful in this regard. We present the known localizing and lateralizing signs based on this system. PMID:23323131

  19. Optimized methods for epilepsy therapy development using an etiologically realistic model of focal epilepsy in the rat

    PubMed Central

    Eastman, Clifford L.; Fender, Jason S.; Temkin, Nancy R.; D’Ambrosio, Raimondo

    2015-01-01

    Conventionally developed antiseizure drugs fail to control epileptic seizures in about 30% of patients, and no treatment prevents epilepsy. New etiologically realistic, syndrome-specific epilepsy models are expected to identify better treatments by capturing currently unknown ictogenic and epileptogenic mechanisms that operate in the corresponding patient populations. Additionally, the use of electrocorticography permits better monitoring of epileptogenesis and the full spectrum of acquired seizures, including focal nonconvulsive seizures that are typically difficult to treat in humans. Thus, the combined use of etiologically realistic models and electrocorticography may improve our understanding of the genesis and progression of epilepsy, and facilitate discovery and translation of novel treatments. However, this approach is labor intensive and must be optimized. To this end, we used an etiologically realistic rat model of posttraumatic epilepsy, in which the initiating fluid percussion injury closely replicates contusive closed-head injury in humans, and has been adapted to maximize epileptogenesis and focal non-convulsive seizures. We obtained week-long 5-electrode electrocorticography 1 month post-injury, and used a Monte-Carlo-based non-parametric bootstrap strategy to test the impact of electrode montage design, duration-based seizure definitions, group size and duration of recordings on the assessment of posttraumatic epilepsy, and on statistical power to detect antiseizure and antiepileptogenic treatment effects. We found that use of seizure definition based on clinical criteria rather than event duration, and of recording montages closely sampling the activity of epileptic foci, maximize the power to detect treatment effects. Detection of treatment effects was marginally improved by prolonged recording, and 24 h recording epochs were sufficient to provide 80% power to detect clinically interesting seizure control or prevention of seizures with small groups

  20. Progressive contralateral hippocampal atrophy following surgery for medically refractory temporal lobe epilepsy.

    PubMed

    Elliott, Cameron A; Gross, Donald W; Wheatley, B Matt; Beaulieu, Christian; Sankar, Tejas

    2016-09-01

    Determine the extent and time course of volumetric changes in the contralateral hippocampus following surgery for medically refractory temporal lobe epilepsy (TLE). Serial T1-weighted MRI brain scans were obtained in 26 TLE patients pre- and post-temporal lobe epilepsy surgery as well as in 12 control subjects of similar age. Patients underwent either anterior temporal lobectomy (ATL) or selective amygdalohippocampectomy (SAH). Blinded, manual hippocampal volumetry (head, body, and tail) was performed in two groups: 1) two scan group [ATL (n=6); SAH (n=10)], imaged pre-surgery and on average at 5.4 years post-surgery; and 2) longitudinal group [ATL (n=8); SAH (n=2)] imaged pre-surgery and on post-operative day 1, 2, 3, 6, 60, 120 and a delayed time point (average 2.4 years). In the two scan group, there was atrophy by 12% of the unresected contralateral hippocampus (p<0.001), with atrophy being most pronounced (27%) in the hippocampal body (p<0.001) with no significant differences seen for the hippocampal head or tail. In the longitudinal group, significant atrophy was also observed for the whole hippocampus and the body with atrophy seen as early as post-operative day #1 which progressed significantly over the first post-operative week (1.3%/day and 3.0%./day, respectively) before stabilizing over the long-term to a 13% reduction in total volume. There was no significant difference in atrophy compared by surgical approach (ATL vs. SAH; p=0.94) or side (p=0.31); however, atrophy was significantly more pronounced in patients with ongoing post-operative seizures (hippocampal body, p=0.019; whole hippocampus, p=0.048). There were no detectable post-operative neuropsychological deficits attributable to contralateral hippocampal atrophy. Significant contralateral hippocampal atrophy occurs following TLE surgery, which begins immediately and progresses over the first post-operative week. The observation that seizure free patients had significantly less atrophy of the

  1. Childhood onset temporal lobe epilepsy: Beyond hippocampal sclerosis.

    PubMed

    Mühlebner, Angelika; Breu, Markus; Kasprian, Gregor; Schmook, Maria T; Stefanits, Harald; Scholl, Theresa; Samueli, Sharon; Gröppel, Gudrun; Dressler, Anastasia; Prayer, Daniela; Czech, Thomas; Hainfellner, Johannes A; Feucht, Martha

    2016-03-01

    Hippocampal Sclerosis (HS) is widely recognized as a significant underlying cause of drug-resistant temporal lobe epilepsy (TLE) in adults. In contrast, HS is a rare finding in pediatric surgical series, and a higher incidence of HS associated with cortical dysplasia (i.e. FCD type IIIa according to the new ILAE classification) than in adult series has been reported. Data about the electro-clinical characteristics of this subgroup are scarce. We studied 15 children and adolescents with drug-resistant TLE and HS who had anterior temporal lobe resection at our center with regard to electroclinical characteristics, MRI features and histopathology. Children in whom histopathology was consistent with Focal Cortical Dysplasia (FCD) type IIIa (n = 7) were compared with those who had HS only (n = 8). Clinical characteristics associated with this highly selective subset of patients with FCD type IIIa were: the presence of febrile seizures during infancy, a shorter duration of active epilepsy and a lower age at epilepsy surgery. In addition, there were non-significant trends towards more extended abnormalities on both EEG and neuroimaging. We were, however, not able to find group differences with respect to neuropathologic subtyping of the HS. We present the first detailed description and comprehensive data analysis of children with FCD type IIIa. According to our results, this patient group seems to show a distinct clinical phenotype. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  2. Evaluation of a novel median power spectrogram for seizure detection by non-neurophysiologists.

    PubMed

    Yan, Peter; Melman, Tamar; Yan, Sherry; Otgonsuren, Munkhzul; Grinspan, Zachary

    2017-08-01

    (1) To evaluate how well resident physicians use a novel EEG spectral analysis tool (the median power spectrogram; MPS) to detect seizures. (2) To assess the capability of the MPS to identify different seizure types. 120 EEG records from children with intractable seizures were converted to MPS by taking the median power across leads and using multi-taper spectral estimation. Twelve blinded neurology residents were trained to interpret the spectrogram with a five-minute video tutorial and post-test. Two residents independently assessed each set for presence of seizures. Their performance was compared to seizures identified using conventional EEG. Two blinded neurologists separately reviewed the EEGs and spectrograms to independently categorize the seizures. Their results were used to determine the spectrogram's capability to reveal seizures and visualize different seizure types for the user. Three key MPS features distinguished seizures from inter-ictal background: power difference relative to background, down-sloping resonance bands, and power in high frequencies. Using these features, residents identified seizures with 77% sensitivity and 72% specificity. 86% (51/59) of focal seizures and 81% (22/27) of generalized seizures were detected by at least one resident. Missed seizures included brief (<60s) seizures, tonic seizures, seizures with predominant delta (0-4Hz) activity, and seizures evident primarily in supplementary low temporal leads. The MPS is a novel qEEG modality that requires minimal training to interpret. It enables physicians without extensive neurophysiology training to identify seizures with sensitivity and specificity comparable to more complex multi-modal qEEG displays. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  3. Differentiability of simulated MEG hippocampal, medial temporal and neocortical temporal epileptic spike activity.

    PubMed

    Stephen, Julia M; Ranken, Doug M; Aine, Cheryl J; Weisend, Michael P; Shih, Jerry J

    2005-12-01

    Previous studies have shown that magnetoencephalography (MEG) can measure hippocampal activity, despite the cylindrical shape and deep location in the brain. The current study extended this work by examining the ability to differentiate the hippocampal subfields, parahippocampal cortex, and neocortical temporal sources using simulated interictal epileptic activity. A model of the hippocampus was generated on the MRIs of five subjects. CA1, CA3, and dentate gyrus of the hippocampus were activated as well as entorhinal cortex, presubiculum, and neocortical temporal cortex. In addition, pairs of sources were activated sequentially to emulate various hypotheses of mesial temporal lobe seizure generation. The simulated MEG activity was added to real background brain activity from the five subjects and modeled using a multidipole spatiotemporal modeling technique. The waveforms and source locations/orientations for hippocampal and parahippocampal sources were differentiable from neocortical temporal sources. In addition, hippocampal and parahippocampal sources were differentiated to varying degrees depending on source. The sequential activation of hippocampal and parahippocampal sources was adequately modeled by a single source; however, these sources were not resolvable when they overlapped in time. These results suggest that MEG has the sensitivity to distinguish parahippocampal and hippocampal spike generators in mesial temporal lobe epilepsy.

  4. Preictal Activity of Subicular, CA1, and Dentate Gyrus Principal Neurons in the Dorsal Hippocampus before Spontaneous Seizures in a Rat Model of Temporal Lobe Epilepsy

    PubMed Central

    Fujita, Satoshi; Toyoda, Izumi; Thamattoor, Ajoy K.

    2014-01-01

    Previous studies suggest that spontaneous seizures in patients with temporal lobe epilepsy might be preceded by increased action potential firing of hippocampal neurons. Preictal activity is potentially important because it might provide new opportunities for predicting when a seizure is about to occur and insight into how spontaneous seizures are generated. We evaluated local field potentials and unit activity of single, putative excitatory neurons in the subiculum, CA1, CA3, and dentate gyrus of the dorsal hippocampus in epileptic pilocarpine-treated rats as they experienced spontaneous seizures. Average action potential firing rates of neurons in the subiculum, CA1, and dentate gyrus, but not CA3, increased significantly and progressively beginning 2–4 min before locally recorded spontaneous seizures. In the subiculum, CA1, and dentate gyrus, but not CA3, 41–57% of neurons displayed increased preictal activity with significant consistency across multiple seizures. Much of the increased preictal firing of neurons in the subiculum and CA1 correlated with preictal theta activity, whereas preictal firing of neurons in the dentate gyrus was independent of theta. In addition, some CA1 and dentate gyrus neurons displayed reduced firing rates preictally. These results reveal that different hippocampal subregions exhibit differences in the extent and potential underlying mechanisms of preictal activity. The finding of robust and significantly consistent preictal activity of subicular, CA1, and dentate neurons in the dorsal hippocampus, despite the likelihood that many seizures initiated in other brain regions, suggests the existence of a broader neuronal network whose activity changes minutes before spontaneous seizures initiate. PMID:25505320

  5. A testbed to explore the optimal electrical stimulation parameters for suppressing inter-ictal spikes in human hippocampal slices.

    PubMed

    Min-Chi Hsiao; Pen-Ning Yu; Dong Song; Liu, Charles Y; Heck, Christi N; Millett, David; Berger, Theodore W

    2014-01-01

    New interventions using neuromodulatory devices such as vagus nerve stimulation, deep brain stimulation and responsive neurostimulation are available or under study for the treatment of refractory epilepsy. Since the actual mechanisms of the onset and termination of the seizure are still unclear, most researchers or clinicians determine the optimal stimulation parameters through trial-and-error procedures. It is necessary to further explore what types of electrical stimulation parameters (these may include stimulation frequency, amplitude, duration, interval pattern, and location) constitute a set of optimal stimulation paradigms to suppress seizures. In a previous study, we developed an in vitro epilepsy model using hippocampal slices from patients suffering from mesial temporal lobe epilepsy. Using a planar multi-electrode array system, inter-ictal activity from human hippocampal slices was consistently recorded. In this study, we have further transferred this in vitro seizure model to a testbed for exploring the possible neurostimulation paradigms to inhibit inter-ictal spikes. The methodology used to collect the electrophysiological data, the approach to apply different electrical stimulation parameters to the slices are provided in this paper. The results show that this experimental testbed will provide a platform for testing the optimal stimulation parameters of seizure cessation. We expect this testbed will expedite the process for identifying the most effective parameters, and may ultimately be used to guide programming of new stimulating paradigms for neuromodulatory devices.

  6. [Neuroprotective effect of naloxone in brain damage caused by repeated febrile seizure].

    PubMed

    Shan, Ying; Qin, Jiong; Chang, Xing-zhi; Yang, Zhi-xian

    2004-04-01

    The brain damage caused by repeated febrile seizure (FS) during developing age is harmful to the intellectual development of children. So how to decrease the related damage is a very important issue. The main purpose of the present study was to find out whether the non-specific opiate antagonist naloxone at low dose has the neuroprotective effect on seizure-induced brain damage. Warm water induced rat FS model was developed in this study. Forty-seven rats were randomly divided into two groups: normal control group (n = 10) and hyperthermic seizure groups (n = 37). The latter was further divided into FS control group (n = 13) and naloxone-treated group (n = 24). The dose of naloxone is different in two naloxone-treated groups (12/each group), in one group the dose was 1 mg/kg, in the other one 2 mg/kg. Seven febrile seizures were induced in each rat of hyperthermic seizure groups with the interval of 2 days. The rats were weighed and injected intraperitoneally with naloxone once the FS occurred in naloxone-treated group, while the rats of the other groups were injected with 0.9% sodium chloride. Latency, duration and grade of FS in different groups were observed and compared. HE-staining and the electron microscopy (EM) were used to detect the morphologic and ultrastructural changes of hippocampal neurons. In naloxone-treated group, the rats' FS duration and FS grade (5.02 +/- 0.63, 2.63 +/- 0.72) were significantly lower (t = 5.508, P < 0.01; t = 8.439, P < 0.01) than those in FS control group (7.70 +/- 2.25 min, 4.52 +/- 0.49), although no significant gap was observed on FS latency between them. In FS control group, HE-staining pattern of hippocampal CA(1) and CA(2) showed lots of disordered neurons with confused polarity and vacuoles formed. Nuclei were with various size, some rounded and some oblong. While in naloxone-treated groups, the arrangement of neurons was regular, only a small quantity of neurons had changed polarity and vacuoles formed. Most nuclei

  7. A minimum of 3 months of dietary fish oil supplementation is required to raise amygdaloid afterdischarge seizure thresholds in rats--implications for treating complex partial seizures.

    PubMed

    Taha, Ameer Y; Trepanier, Marc-Olivier; Ciobanu, Flaviu A; Taha, Nadeen M; Ahmed, Muaz; Zeng, Qiudi; Cheuk, Waiyin I; Ip, Bryan; Filo, Elvis; Scott, Brian W; Burnham, W M; Bazinet, Richard P

    2013-04-01

    Complex partial seizures, which typically originate in limbic structures such as the amygdala, are often resistant to antiseizure medications. Our goal was to investigate the effects of chronic dietary supplementation with n-3 polyunsaturated fatty acids (PUFAs) derived from fish oil on seizure thresholds in the amygdala, as well as on blood and brain PUFA levels. The acute effects of injected n-3 PUFAs--eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)--were also tested in the maximal pentylenetetrazol (PTZ) seizure model. In amygdala-implanted subjects, fish oil supplementation significantly increased amygdaloid afterdischarge thresholds, as compared with controls at 3, 5, and 7 months after the start of supplementation. Fish oil supplementation also increased serum EPA and DHA concentrations. DHA concentration in the pyriform-amygdala area increased in the fish-oil treated group by 17-34%, but this effect did not reach statistical significance (P=0.065). DHA significantly increased the latency to seizure onset in the PTZ seizure model, whereas EPA had no significant effect. These observations suggest that chronic dietary fish oil supplementation can raise focal amygdaloid seizure thresholds and that this effect is likely mediated by DHA rather than by EPA. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Radiation Dose–Dependent Hippocampal Atrophy Detected With Longitudinal Volumetric Magnetic Resonance Imaging

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Seibert, Tyler M.; Karunamuni, Roshan; Bartsch, Hauke

    Purpose: After radiation therapy (RT) to the brain, patients often experience memory impairment, which may be partially mediated by damage to the hippocampus. Hippocampal sparing in RT planning is the subject of recent and ongoing clinical trials. Calculating appropriate hippocampal dose constraints would be improved by efficient in vivo measurements of hippocampal damage. In this study we sought to determine whether brain RT was associated with dose-dependent hippocampal atrophy. Methods and Materials: Hippocampal volume was measured with magnetic resonance imaging (MRI) in 52 patients who underwent fractionated, partial brain RT for primary brain tumors. Study patients had high-resolution, 3-dimensional volumetric MRI beforemore » and 1 year after RT. Images were processed using software with clearance from the US Food and Drug Administration and Conformité Européene marking for automated measurement of hippocampal volume. Automated results were inspected visually for accuracy. Tumor and surgical changes were censored. Mean hippocampal dose was tested for correlation with hippocampal atrophy 1 year after RT. Average hippocampal volume change was also calculated for hippocampi receiving high (>40 Gy) or low (<10 Gy) mean RT dose. A multivariate analysis was conducted with linear mixed-effects modeling to evaluate other potential predictors of hippocampal volume change, including patient (random effect), age, hemisphere, sex, seizure history, and baseline volume. Statistical significance was evaluated at α = 0.05. Results: Mean hippocampal dose was significantly correlated with hippocampal volume loss (r=−0.24, P=.03). Mean hippocampal volume was significantly reduced 1 year after high-dose RT (mean −6%, P=.009) but not after low-dose RT. In multivariate analysis, both RT dose and patient age were significant predictors of hippocampal atrophy (P<.01). Conclusions: The hippocampus demonstrates radiation dose–dependent atrophy after treatment for

  9. Seizure entrainment with polarizing low-frequency electric fields in a chronic animal epilepsy model

    NASA Astrophysics Data System (ADS)

    Sunderam, Sridhar; Chernyy, Nick; Peixoto, Nathalia; Mason, Jonathan P.; Weinstein, Steven L.; Schiff, Steven J.; Gluckman, Bruce J.

    2009-08-01

    Neural activity can be modulated by applying a polarizing low-frequency (Lt100 Hz) electric field (PLEF). Unlike conventional pulsed stimulation, PLEF stimulation has a graded, modulatory effect on neuronal excitability, and permits the simultaneous recording of neuronal activity during stimulation suitable for continuous feedback control. We tested a prototype system that allows for simultaneous PLEF stimulation with minimal recording artifact in a chronic tetanus toxin animal model (rat) of hippocampal epilepsy with spontaneous seizures. Depth electrode local field potentials recorded during seizures revealed a characteristic pattern of field postsynaptic potentials (fPSPs). Sinusoidal voltage-controlled PLEF stimulation (0.5-25 Hz) was applied in open-loop cycles radially across the CA3 of ventral hippocampus. For stimulated seizures, fPSPs were transiently entrained with the PLEF waveform. Statistical significance of entrainment was assessed with Thomson's harmonic F-test, with 45/132 stimulated seizures in four animals individually demonstrating significant entrainment (p < 0.04). Significant entrainment for multiple presentations at the same frequency (p < 0.01) was observed in three of four animals in 42/64 stimulated seizures. This is the first demonstration in chronically implanted freely behaving animals of PLEF modulation of neural activity with simultaneous recording.

  10. Unexpected marked seizure improvement in paediatric epilepsy surgery candidates.

    PubMed

    Hoei-Hansen, Christina E; Mathiasen, René; Uldall, Peter

    2017-02-01

    Epilepsy surgery is performed based on the assumption that medical refractory epilepsy will continue. Rarely seizure freedom occurs before surgery is performed, while the patient is being evaluated as an epilepsy surgery candidate. The aim of this study was to describe the number of children withdrawn from an epilepsy surgery programme due to unexpected seizure improvement. We retrospectively studied 173 children under 18 years with medical refractory epilepsy referred for epilepsy surgery between 1996 and 2010. Medical records were reviewed in 2012 and 2015. At the first evaluation point in 2012, 13 patients were withdrawn from the epilepsy surgery programme due to unexpected marked improvement. In 2015, 6 of them were still seizure free. They had unexpected seizure freedom due to change in AED treatment (n=3) or after a febrile episode (n=3). The mean number of years they had had seizures was 3.4 years (range 0.6-6.2 years) and the number of seizures at inclusion was 209 per month (range 6-750 per month). The duration of follow-up was 6.6 years after inclusion into the epilepsy surgery programme (range 4.0-13.0 years). The aetiology of the epilepsy for these patients was heterotopia (n=1), focal cortical dysplasia (n=3), infarction (n=1) and unknown, with normal MRI (n=1). They all had an IQ in the normal range. Two of the remaining 7 children were operated later. Unexpected seizure control may occur during epilepsy surgery evaluation. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  11. Hippocampal sclerosis in advanced age: clinical and pathological features.

    PubMed

    Nelson, Peter T; Schmitt, Frederick A; Lin, Yushun; Abner, Erin L; Jicha, Gregory A; Patel, Ela; Thomason, Paula C; Neltner, Janna H; Smith, Charles D; Santacruz, Karen S; Sonnen, Joshua A; Poon, Leonard W; Gearing, Marla; Green, Robert C; Woodard, John L; Van Eldik, Linda J; Kryscio, Richard J

    2011-05-01

    Hippocampal sclerosis is a relatively common neuropathological finding (∼10% of individuals over the age of 85 years) characterized by cell loss and gliosis in the hippocampus that is not explained by Alzheimer's disease. Hippocampal sclerosis pathology can be associated with different underlying causes, and we refer to hippocampal sclerosis in the aged brain as hippocampal sclerosis associated with ageing. Much remains unknown about hippocampal sclerosis associated with ageing. We combined three different large autopsy cohorts: University of Kentucky Alzheimer's Disease Centre, the Nun Study and the Georgia Centenarian Study to obtain a pool of 1110 patients, all of whom were evaluated neuropathologically at the University of Kentucky. We focused on the subset of cases with neuropathology-confirmed hippocampal sclerosis (n=106). For individuals aged≥95 years at death (n=179 in our sample), each year of life beyond the age of 95 years correlated with increased prevalence of hippocampal sclerosis pathology and decreased prevalence of 'definite' Alzheimer's disease pathology. Aberrant TAR DNA protein 43 immunohistochemistry was seen in 89.9% of hippocampal sclerosis positive patients compared with 9.7% of hippocampal sclerosis negative patients. TAR DNA protein 43 immunohistochemistry can be used to demonstrate that the disease is usually bilateral even when hippocampal sclerosis pathology is not obvious by haematoxylin and eosin stains. TAR DNA protein 43 immunohistochemistry was negative on brain sections from younger individuals (n=10) after hippocampectomy due to seizures, who had pathologically confirmed hippocampal sclerosis. There was no association between cases with hippocampal sclerosis associated with ageing and apolipoprotein E genotype. Age of death and clinical features of hippocampal sclerosis associated with ageing (with or without aberrant TAR DNA protein 43) were distinct from previously published cases of frontotemporal lobar degeneration TAR

  12. Hippocampal sclerosis in advanced age: clinical and pathological features

    PubMed Central

    Schmitt, Frederick A.; Lin, Yushun; Abner, Erin L.; Jicha, Gregory A.; Patel, Ela; Thomason, Paula C.; Neltner, Janna H.; Smith, Charles D.; Santacruz, Karen S.; Sonnen, Joshua A.; Poon, Leonard W.; Gearing, Marla; Green, Robert C.; Woodard, John L.; Van Eldik, Linda J.; Kryscio, Richard J.

    2011-01-01

    Hippocampal sclerosis is a relatively common neuropathological finding (∼10% of individuals over the age of 85 years) characterized by cell loss and gliosis in the hippocampus that is not explained by Alzheimer’s disease. Hippocampal sclerosis pathology can be associated with different underlying causes, and we refer to hippocampal sclerosis in the aged brain as hippocampal sclerosis associated with ageing. Much remains unknown about hippocampal sclerosis associated with ageing. We combined three different large autopsy cohorts: University of Kentucky Alzheimer’s Disease Centre, the Nun Study and the Georgia Centenarian Study to obtain a pool of 1110 patients, all of whom were evaluated neuropathologically at the University of Kentucky. We focused on the subset of cases with neuropathology-confirmed hippocampal sclerosis (n = 106). For individuals aged ≥95 years at death (n = 179 in our sample), each year of life beyond the age of 95 years correlated with increased prevalence of hippocampal sclerosis pathology and decreased prevalence of ‘definite’ Alzheimer’s disease pathology. Aberrant TAR DNA protein 43 immunohistochemistry was seen in 89.9% of hippocampal sclerosis positive patients compared with 9.7% of hippocampal sclerosis negative patients. TAR DNA protein 43 immunohistochemistry can be used to demonstrate that the disease is usually bilateral even when hippocampal sclerosis pathology is not obvious by haematoxylin and eosin stains. TAR DNA protein 43 immunohistochemistry was negative on brain sections from younger individuals (n = 10) after hippocampectomy due to seizures, who had pathologically confirmed hippocampal sclerosis. There was no association between cases with hippocampal sclerosis associated with ageing and apolipoprotein E genotype. Age of death and clinical features of hippocampal sclerosis associated with ageing (with or without aberrant TAR DNA protein 43) were distinct from previously published cases of frontotemporal lobar

  13. Neuronal carbonic anhydrase VII provides GABAergic excitatory drive to exacerbate febrile seizures

    PubMed Central

    Ruusuvuori, Eva; Huebner, Antje K; Kirilkin, Ilya; Yukin, Alexey Y; Blaesse, Peter; Helmy, Mohamed; Jung Kang, Hyo; El Muayed, Malek; Christopher Hennings, J; Voipio, Juha; Šestan, Nenad; Hübner, Christian A; Kaila, Kai

    2013-01-01

    Brain carbonic anhydrases (CAs) are known to modulate neuronal signalling. Using a novel CA VII (Car7) knockout (KO) mouse as well as a CA II (Car2) KO and a CA II/VII double KO, we show that mature hippocampal pyramidal neurons are endowed with two cytosolic isoforms. CA VII is predominantly expressed by neurons starting around postnatal day 10 (P10). The ubiquitous isoform II is expressed in neurons at P20. Both isoforms enhance bicarbonate-driven GABAergic excitation during intense GABAA-receptor activation. P13–14 CA VII KO mice show behavioural manifestations atypical of experimental febrile seizures (eFS) and a complete absence of electrographic seizures. A low dose of diazepam promotes eFS in P13–P14 rat pups, whereas seizures are blocked at higher concentrations that suppress breathing. Thus, the respiratory alkalosis-dependent eFS are exacerbated by GABAergic excitation. We found that CA VII mRNA is expressed in the human cerebral cortex before the age when febrile seizures (FS) occur in children. Our data indicate that CA VII is a key molecule in age-dependent neuronal pH regulation with consequent effects on generation of FS. PMID:23881097

  14. New clinicopathological associations and histoprognostic markers in ILAE types of hippocampal sclerosis.

    PubMed

    Calderon-Garcidueñas, Ana Laura; Mathon, Bertrand; Lévy, Pierre; Bertrand, Anne; Mokhtari, Karima; Samson, Véronique; Thuriès, Valérie; Lambrecq, Virginie; Nguyen, Vi-Huong Michel; Dupont, Sophie; Adam, Claude; Baulac, Michel; Clémenceau, Stéphane; Duyckaerts, Charles; Navarro, Vincent; Bielle, Franck

    2018-02-24

    Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is a heterogeneous syndrome. Surgery results in seizure freedom for most pharmacoresistant patients, but the epileptic and cognitive prognosis remains variable. The 2013 International League Against Epilepsy (ILAE) histopathological classification of hippocampal sclerosis (HS) has fostered research to understand MTLE-HS heterogeneity. We investigated the associations between histopathological features (ILAE types, hypertrophic CA4 neurons, granule cell layer alterations, CD34 immunopositive cells) and clinical features (presurgical history, postsurgical outcome) in a monocentric series of 247 MTLE-HS patients treated by surgery. NeuN, GFAP and CD34 immunostainings and a double independent pathological examination were performed. 186 samples were type 1, 47 type 2, 7 type 3 and 7 samples were gliosis only but no neuronal loss (noHS). In the type 1, hypertrophic CA4 neurons were associated with a worse postsurgical outcome and granule cell layer duplication was associated with generalized seizures and episodes of status epilepticus. In the type 2, granule cell layer duplication was associated with generalized seizures. CD34+ stellate cells were more frequent in the type 2, type 3 and in noHS. These cells had a Nestin and SOX2 positive, immature neural immunophenotype. Patients with nodules of CD34+ cells had more frequent dysmnesic auras. CD34+ stellate cells in scarce pattern were associated with higher ratio of normal MRI and of stereo-electroencephalographic studies. CD34+ cells were associated with a trend for a better postsurgical outcome. Among CD34+ cases, we proposed a new entity of BRAF V600E positive HS and we described three hippocampal multinodular and vacuolating neuronal tumors. To conclude, our data identified new clinicopathological associations with ILAE types. They showed the prognostic value of CA4 hypertrophic neurons. They highlighted CD34+ stellate cells and BRAF V600E as

  15. Epileptic seizures as condensed sleep: an analysis of network dynamics from electroencephalogram signals.

    PubMed

    Gast, Heidemarie; Müller, Markus; Rummel, Christian; Roth, Corinne; Mathis, Johannes; Schindler, Kaspar; Bassetti, Claudio L

    2014-06-01

    Both deepening sleep and evolving epileptic seizures are associated with increasing slow-wave activity. Larger-scale functional networks derived from electroencephalogram indicate that in both transitions dramatic changes of communication between brain areas occur. During seizures these changes seem to be 'condensed', because they evolve more rapidly than during deepening sleep. Here we set out to assess quantitatively functional network dynamics derived from electroencephalogram signals during seizures and normal sleep. Functional networks were derived from electroencephalogram signals from wakefulness, light and deep sleep of 12 volunteers, and from pre-seizure, seizure and post-seizure time periods of 10 patients suffering from focal onset pharmaco-resistant epilepsy. Nodes of the functional network represented electrical signals recorded by single electrodes and were linked if there was non-random cross-correlation between the two corresponding electroencephalogram signals. Network dynamics were then characterized by the evolution of global efficiency, which measures ease of information transmission. Global efficiency was compared with relative delta power. Global efficiency significantly decreased both between light and deep sleep, and between pre-seizure, seizure and post-seizure time periods. The decrease of global efficiency was due to a loss of functional links. While global efficiency decreased significantly, relative delta power increased except between the time periods wakefulness and light sleep, and pre-seizure and seizure. Our results demonstrate that both epileptic seizures and deepening sleep are characterized by dramatic fragmentation of larger-scale functional networks, and further support the similarities between sleep and seizures. © 2013 European Sleep Research Society.

  16. Left Frontal Meningioangiomatosis Associated with Type IIIc Focal Cortical Dysplasia Causing Refractory Epilepsy and Literature Review.

    PubMed

    Roux, Alexandre; Mellerio, Charles; Lechapt-Zalcman, Emmanuelle; Still, Megan; Zerah, Michel; Bourgeois, Marie; Pallud, Johan

    2018-06-01

    We report the surgical management of a lesional drug-resistant epilepsy caused by a meningioangiomatosis associated with a type IIIc focal cortical dysplasia located in the left supplementary motor area in a young male patient. A first anatomically based partial surgical resection was performed on an 11-year-old under general anesthesia without intraoperative mapping, which allowed for postoperative seizure control (Engel IA) for 6 years. The patient then exhibited intractable right sensatory and aphasic focal onset seizures despite 2 appropriate antiepileptic drugs. A second functional-based surgical resection was performed using intraoperative corticosubcortical functional mapping with direct electrical stimulation under awake conditions. A complete surgical resection was performed, and a left partial supplementary motor area syndrome was observed. At 6 months postoperatively, the patient is seizure free (Engel IA) with an ongoing decrease in antiepileptic drug therapy. Intraoperative functional brain mapping can be applied to preserve the brain function and networks around a meningioangiomatosis to facilitate the resection of potentially epileptogenic perilesional dysplastic cortex and to tailor the extent of resection to functional boundaries. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Hippocampal protection in mice with an attenuated inflammatory monocyte response to acute CNS picornavirus infection

    PubMed Central

    Howe, Charles L.; LaFrance-Corey, Reghann G.; Sundsbak, Rhianna S.; Sauer, Brian M.; LaFrance, Stephanie J.; Buenz, Eric J.; Schmalstieg, William F.

    2012-01-01

    Neuronal injury during acute viral infection of the brain is associated with the development of persistent cognitive deficits and seizures in humans. In C57BL/6 mice acutely infected with the Theiler's murine encephalomyelitis virus, hippocampal CA1 neurons are injured by a rapid innate immune response, resulting in profound memory deficits. In contrast, infected SJL and B6xSJL F1 hybrid mice exhibit essentially complete hippocampal and memory preservation. Analysis of brain-infiltrating leukocytes revealed that SJL mice mount a sharply attenuated inflammatory monocyte response as compared to B6 mice. Bone marrow transplantation experiments isolated the attenuation to the SJL immune system. Adoptive transfer of B6 inflammatory monocytes into acutely infected B6xSJL hosts converted these mice to a hippocampal damage phenotype and induced a cognitive deficit marked by failure to recognize a novel object. These findings show that inflammatory monocytes are the critical cellular mediator of hippocampal injury during acute picornavirus infection of the brain. PMID:22848791

  18. Dynamics of convulsive seizure termination and postictal generalized EEG suppression

    PubMed Central

    Bauer, Prisca R.; Thijs, Roland D.; Lamberts, Robert J.; Velis, Demetrios N.; Visser, Gerhard H.; Tolner, Else A.; Sander, Josemir W.; Lopes da Silva, Fernando H.; Kalitzin, Stiliyan N.

    2017-01-01

    Abstract It is not fully understood how seizures terminate and why some seizures are followed by a period of complete brain activity suppression, postictal generalized EEG suppression. This is clinically relevant as there is a potential association between postictal generalized EEG suppression, cardiorespiratory arrest and sudden death following a seizure. We combined human encephalographic seizure data with data of a computational model of seizures to elucidate the neuronal network dynamics underlying seizure termination and the postictal generalized EEG suppression state. A multi-unit computational neural mass model of epileptic seizure termination and postictal recovery was developed. The model provided three predictions that were validated in EEG recordings of 48 convulsive seizures from 48 subjects with refractory focal epilepsy (20 females, age range 15–61 years). The duration of ictal and postictal generalized EEG suppression periods in human EEG followed a gamma probability distribution indicative of a deterministic process (shape parameter 2.6 and 1.5, respectively) as predicted by the model. In the model and in humans, the time between two clonic bursts increased exponentially from the start of the clonic phase of the seizure. The terminal interclonic interval, calculated using the projected terminal value of the log-linear fit of the clonic frequency decrease was correlated with the presence and duration of postictal suppression. The projected terminal interclonic interval explained 41% of the variation in postictal generalized EEG suppression duration (P < 0.02). Conversely, postictal generalized EEG suppression duration explained 34% of the variation in the last interclonic interval duration. Our findings suggest that postictal generalized EEG suppression is a separate brain state and that seizure termination is a plastic and autonomous process, reflected in increased duration of interclonic intervals that determine the duration of postictal

  19. The role of executive functioning in memory performance in pediatric focal epilepsy

    PubMed Central

    Sepeta, Leigh N.; Casaletto, Kaitlin Blackstone; Terwilliger, Virginia; Facella-Ervolini, Joy; Sady, Maegan; Mayo, Jessica; Gaillard, William D.; Berl, Madison M.

    2016-01-01

    Objective Learning and memory are essential for academic success and everyday functioning, but the pattern of memory skills and its relationship to executive functioning in children with focal epilepsy is not fully delineated. We address a gap in the literature by examining the relationship between memory and executive functioning in a pediatric focal epilepsy population. Methods Seventy children with focal epilepsy and 70 typically developing children matched on age, intellectual functioning, and gender underwent neuropsychological assessment, including measures of intelligence (WASI/DAS), as well as visual (CMS Dot Locations) and verbal episodic memory (WRAML Story Memory and CVLT-C). Executive functioning was measured directly (WISC-IV Digit Span Backward; CELF-IV Recalling Sentences) and by parent report (Behavior Rating Inventory of Executive Function (BRIEF)). Results Children with focal epilepsy had lower delayed free recall scores than controls across visual and verbal memory tasks (p = 0.02; partial η2 = .12). In contrast, recognition memory performance was similar for patients and controls (p = 0.36; partial η2 = .03). Children with focal epilepsy demonstrated difficulties in working memory (p = 0.02; partial η2 = .08) and planning/organization (p = 0.02) compared to controls. Working memory predicted 9–19% of the variance in delayed free recall for verbal and visual memory; organization predicted 9–10% of the variance in verbal memory. Patients with both left and right focal epilepsy demonstrated more difficulty on verbal versus visual tasks (p = 0.002). Memory performance did not differ by location of seizure foci (temporal vs. extra-temporal, frontal vs. extra-frontal). Significance Children with focal epilepsy demonstrated memory ability within age-level expectations, but delayed free recall was inefficient compared to typically developing controls. Memory difficulties were not related to general cognitive impairment or seizure localization

  20. Intra-hippocampal microinjection of oxytocin produced antiepileptic effect on the pentylenetetrazol-induced epilepsy in rats.

    PubMed

    Erfanparast, Amir; Tamaddonfard, Esmaeal; Henareh-Chareh, Farzin

    2017-08-01

    In addition to its role as a circulating hormone, oxytocin can also act as a neurotransmitter and a neuromodulator within the brain. In this study, we investigated the intra-hippocampal effect of oxytocin on an experimental seizure model induced by pentylenetetrazole (PTZ) in rats. We also used atosiban (oxytocin antagonist), diazepam and flumazenil (gamma-aminobutyric acid or GABA-benzodiazepine receptor agonist and antagonist, respectively) to clarify the involved mechanism. In ketamine-xylazine anesthetized rats, the right and left sides of the dorsal hippocampus (CA1) were implanted with two guide cannulas. Epileptic behaviors were induced by intraperitoneal (ip) injection of PTZ (60mg/kg), and the latency time to onset of first myoclonic jerk, and the duration of epileptic seizures were determined for 30min. Intra-hippocampal microinjections of oxytocin at doses of 10 and 20ng/site, diazepam (100 and 200ng/site) and co-administration of their ineffective doses significantly (p<0.01) increased the onset of first myoclonic jerk and decreased duration of epileptic seizure. Antiepileptic effects of oxytocin (20ng/site) were inhibited by atosiban (20 and 40ng/site) and flumazenil (100 and 200ng/site) pretreatments. On the other hand, prior administration of flumazenil (100 and 200ng/site) and atosiban (20 and 40ng/site) prevented the antiepileptic effects induced by diazepam (100 and 200ng/site). The results of the present study showed that at the level of the hippocampus oxytocin suppressed the severity of epileptic behaviors. A hippocampal GABA-benzodiazepine receptor mechanism may be involved in antiepileptic effect of oxytocin. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  1. Seven tesla MRI improves detection of focal cortical dysplasia in patients with refractory focal epilepsy.

    PubMed

    Veersema, Tim J; Ferrier, Cyrille H; van Eijsden, Pieter; Gosselaar, Peter H; Aronica, Eleonora; Visser, Fredy; Zwanenburg, Jaco M; de Kort, Gerard A P; Hendrikse, Jeroen; Luijten, Peter R; Braun, Kees P J

    2017-06-01

    The aim of this study is to determine whether the use of 7 tesla (T) MRI in clinical practice leads to higher detection rates of focal cortical dysplasias in possible candidates for epilepsy surgery. In our center patients are referred for 7 T MRI if lesional focal epilepsy is suspected, but no abnormalities are detected at one or more previous, sufficient-quality lower-field MRI scans, acquired with a dedicated epilepsy protocol, or when concealed pathology is suspected in combination with MR-visible mesiotemporal sclerosis-dual pathology. We assessed 40 epilepsy patients who underwent 7 T MRI for presurgical evaluation and whose scans (both 7 T and lower field) were discussed during multidisciplinary epilepsy surgery meetings that included a dedicated epilepsy neuroradiologist. We compared the conclusions of the multidisciplinary visual assessments of 7 T and lower-field MRI scans. In our series of 40 patients, multidisciplinary evaluation of 7 T MRI identified additional lesions not seen on lower-field MRI in 9 patients (23%). These findings were guiding in surgical planning. So far, 6 patients underwent surgery, with histological confirmation of focal cortical dysplasia or mild malformation of cortical development. Seven T MRI improves detection of subtle focal cortical dysplasia and mild malformations of cortical development in patients with intractable epilepsy and may therefore contribute to identification of surgical candidates and complete resection of the epileptogenic lesion, and thus to postoperative seizure freedom.

  2. Scalp EEG Ictal Gamma and Beta Activity during Infantile Spasms: Evidence of Focality

    PubMed Central

    Nariai, Hiroki; Beal, Jules; Galanopoulou, Aristea S.; Mowrey, Wenzhu B.; Bickel, Stephan; Sogawa, Yoshimi; Jehle, Rana; Shinnar, Shlomo; Moshé, Solomon L.

    2017-01-01

    Objective We investigated temporal and spatial characteristics of ictal gamma and beta activity on scalp EEG during spasms in patients with West syndrome (WS) to evaluate potential focal cortical onset. Methods A total of 1033 spasms from 34 patients with WS of various etiologies were analyzed in video-EEG using time-frequency analysis. Ictal gamma (35–90 Hz) and beta (15–30 Hz) activities were correlated with visual symmetry of spasms, objective EMG (electromyography) analysis, and etiology of WS. Results Prior to the ictal motor manifestation, focal ictal gamma activity emerged from one hemisphere (71%, 24/34) or from midline (26%, 9/34), and was rarely simultaneously bilateral (3%, 1/34). Focal ictal beta activity emerged from either one hemisphere (68%, 23/34) or from midline (32%, 11/34). Onsets of focal ictal gamma and beta activity were most commonly observed around the parietal areas. Focal ictal gamma activity propagated faster than ictal beta activity to adjacent electrodes (median: 65 vs. 170 ms, p<0.01), and to contralateral hemisphere (median: 100 vs. 170 ms, p=0.01). Asymmetric peak amplitude of ictal gamma activity in the centroparietal areas (C3-P3 vs. C4-P4) correlated with asymmetric semiology. On the other hand, the majority of visually symmetric spasms showed asymmetry in peak amplitude and interhemispheric onset latency difference in both ictal gamma and beta activity. Significance Spasms may be a seizure with focal electrographic onset regardless of visual symmetry. Asymmetric involvement of ictal gamma activity to the centroparietal areas may determine the motor manifestations in WS. Scalp EEG ictal gamma and beta activity may be useful to demonstrate localized seizure onset in infants with WS. PMID:28397999

  3. Early Activation of Ventral Hippocampus and Subiculum during Spontaneous Seizures in a Rat Model of Temporal Lobe Epilepsy

    PubMed Central

    Toyoda, Izumi; Bower, Mark R.; Leyva, Fernando

    2013-01-01

    Temporal lobe epilepsy is the most common form of epilepsy in adults. The pilocarpine-treated rat model is used frequently to investigate temporal lobe epilepsy. The validity of the pilocarpine model has been challenged based largely on concerns that seizures might initiate in different brain regions in rats than in patients. The present study used 32 recording electrodes per rat to evaluate spontaneous seizures in various brain regions including the septum, dorsomedial thalamus, amygdala, olfactory cortex, dorsal and ventral hippocampus, substantia nigra, entorhinal cortex, and ventral subiculum. Compared with published results from patients, seizures in rats tended to be shorter, spread faster and more extensively, generate behavioral manifestations more quickly, and produce generalized convulsions more frequently. Similarities to patients included electrographic waveform patterns at seizure onset, variability in sites of earliest seizure activity within individuals, and variability in patterns of seizure spread. Like patients, the earliest seizure activity in rats was recorded most frequently within the hippocampal formation. The ventral hippocampus and ventral subiculum displayed the earliest seizure activity. Amygdala, olfactory cortex, and septum occasionally displayed early seizure latencies, but not above chance levels. Substantia nigra and dorsomedial thalamus demonstrated consistently late seizure onsets, suggesting their unlikely involvement in seizure initiation. The results of the present study reveal similarities in onset sites of spontaneous seizures in patients with temporal lobe epilepsy and pilocarpine-treated rats that support the model's validity. PMID:23825415

  4. Expression and function of the metabotropic purinergic P2Y receptor family in experimental seizure models and patients with drug-refractory epilepsy.

    PubMed

    Alves, Mariana; Gomez-Villafuertes, Rosa; Delanty, Norman; Farrell, Michael A; O'Brien, Donncha F; Miras-Portugal, Maria Teresa; Hernandez, Miguel Diaz; Henshall, David C; Engel, Tobias

    2017-09-01

    ATP is released into the extracellular space during pathologic processes including increased neuronal firing. Once released, ATP acts on P2 receptors including ionotropic P2X and metabotropic P2Y receptors, resulting in changes to glial function and neuronal network excitability. Evidence suggests an involvement of P2Y receptors in the pathogenesis of epilepsy, but there has been no systematic effort to characterize the expression and function of the P2Y receptor family during seizures and in experimental and human epilepsy. Status epilepticus was induced using either intra-amygdala kainic acid or pilocarpine to characterize the acute- and long-term changes in hippocampal P2Y expression. P2Y expression was also investigated in brain tissue from patients with temporal lobe epilepsy. Finally, we analyzed the effects of two specific P2Y agonists, ADP and UTP, on seizure severity and seizure-induced cell death. Both intra-amygdala kainic acid and pilocarpine-induced status epilepticus increased the transcription of the uracil-sensitive P2Y receptors P2ry 2 , P2ry 4 , and P2ry 6 and decreased the transcription of the adenine-sensitive P2Y receptors P2ry 1 , P2ry 12 , P2ry 13 . Protein levels of P2Y 1 , P2Y 2 , P2Y 4 , and P2Y 6 were increased after status epilepticus, whereas P2Y 12 expression was decreased. In the chronic phase, P2ry 1 , P2ry 2 , and P2ry 6 transcription and P2Y 1 , P2Y 2 , and P2Y 12 protein levels were increased with no changes for the other P2Y receptors. In hippocampal samples from patients with temporal lobe epilepsy, P2Y 1 and P2Y 2 protein expression was increased, whereas P2Y 13 levels were lower. Demonstrating a functional contribution of P2Y receptors to seizures, central injection of ADP exacerbated seizure severity, whereas treatment with UTP decreased seizure severity during status epilepticus in mice. The present study is the first to establish the specific hippocampal expression profile and function of the P2Y receptor family after

  5. Neuroprotective effects of idebenone against pilocarpine-induced seizures: modulation of antioxidant status, DNA damage and Na(+), K (+)-ATPase activity in rat hippocampus.

    PubMed

    Ahmed, Maha Ali Eissa

    2014-02-01

    The current study investigated the neuroprotective activity of idebenone against pilocarpine-induced seizures and hippocampal injury in rats. Idebenone is a ubiquinone analog with antioxidant, and ATP replenishment effects. It is well tolerated and has low toxicity. Previous studies reported the protective effects of idebenone against neurodegenerative diseases such as Friedreich's ataxia and Alzheimer's disease. So far, the efficacy of idebenone in experimental models of seizures has not been tested. To achieve this aim, rats were randomly distributed into six groups. Two groups were treated with either normal saline (0.9 %, i.p., control group) or idebenone (200 mg/kg, i.p., Ideb200 group) for three successive days. Rats of the other four groups (P400, Ideb50 + P400, Ideb100 + P400, and Ideb200 + P400) received either saline or idebenone (50, 100, 200 mg/kg, i.p.) for 3 days, respectively followed by a single dose of pilocarpine (400 mg/kg, i.p.). All rats were observed for 6 h post pilocarpine injection. Latency to the first seizure, and percentages of seizures and survival were recorded. Surviving animals were sacrificed, and the hippocampal tissues were separated and used for the measurement of lipid peroxides, total nitrate/nitrite, glutathione and DNA fragmentation levels, in addition to catalase and Na(+), K(+)-ATPase activities. Results revealed that in a dose-dependent manner, idebenone (100, 200 mg/kg) prolonged the latency to the first seizure, elevated the percentage of survival and diminished the percentage of pilocapine-induced seizures in rats. Significant increases in lipid peroxides, total nitrate/nitrite, DNA fragmentation levels and catalase activity, in addition to a significant reduction in glutathione level and Na(+), K(+)-ATPase activity were observed in pilocarpine group. Pre-administration of idebenone (100, 200 mg/kg, i.p.) to pilocarpine-treated rats, significantly reduced lipid peroxides, total nitrate/nitrite, DNA

  6. Characteristic phasic evolution of convulsive seizure in PCDH19-related epilepsy.

    PubMed

    Ikeda, Hiroko; Imai, Katsumi; Ikeda, Hitoshi; Shigematsu, Hideo; Takahashi, Yukitoshi; Inoue, Yushi; Higurashi, Norimichi; Hirose, Shinichi

    2016-03-01

    PCDH19-related epilepsy is a genetic disorder that was first described in 1971, then referred to as "epilepsy and mental retardation limited to females". PCDH19 has recently been identified as the responsible gene, but a detailed characterization of the seizure manifestation based on video-EEG recording is still limited. The purpose of this study was to elucidate features of the seizure semiology in children with PCDH19-related epilepsy. To do this, ictal video-EEG recordings of 26 convulsive seizures in three girls with PCDH19-related epilepsy were analysed. All seizures occurred in clusters, mainly during sleep accompanied by fever. The motor manifestations consisted of six sequential phases: "jerk", "reactive", "mild tonic", "fluttering", "mild clonic", and "postictal". Some phases were brief or lacking in some seizures, whereas others were long or pronounced. In the reactive phase, the patients looked fearful or startled with sudden jerks and turned over reactively. The tonic and clonic components were less intense compared with those of typical tonic-clonic seizures in other types of epilepsy. The fluttering phase was characterised initially by asymmetric, less rhythmic, and less synchronous tremulous movement and was then followed by the subtle clonic phase. Subtle oral automatism was observed in the postictal phase. The reactive, mild tonic, fluttering and mild clonic phases were most characteristic of seizures of PCDH19-related epilepsy. Ictal EEG started bilaterally and was symmetric in some patients but asymmetric in others. It showed asymmetric rhythmic discharges in some seizures at later phases. The electroclinical pattern of the phasic evolution of convulsive seizure suggests a focal onset seizure with secondary generalisation. Based on our findings, we propose that the six unique sequential phases in convulsive seizures suggest the diagnosis of PCDH19-related epilepsy when occurring in clusters with or without high fever in girls. [Published with

  7. Control of seizures in different stages of partial epilepsy: LACO-EXP, a Spanish retrospective study of lacosamide.

    PubMed

    Villanueva, Vicente; López, Francisco Javier; Serratosa, José María; González-Giraldez, Beatriz; Campos, Dulce; Molins, Albert; Rodriguez Uranga, Juan; Mauri, José Angel; Salas-Puig, Javier; Toledo, Manuel; Sánchez-Alvarez, Juan Carlos; Moreno, Antonio; Serrano-Castro, Pedro J; Saiz-Diaz, Rosa Ana; González de la Aleja, Jesús; de la Peña, Pilar; Asensio, Montserrat

    2013-11-01

    Lacosamide is approved as adjunctive therapy for focal epilepsies. The number of antiepileptic drugs (AEDs) tried is associated with prognosis. This multicenter, retrospective, observational study (LACO-EXP) in Spain in 500 adult patients with focal epilepsies examined the efficacy and tolerability of add-on lacosamide. Factors associated with better efficacy/tolerability were analyzed. After 12months, the responder rate (≥50% reduction in seizure frequency) was 57.1%, and the seizure-free rate was 14.9%. Efficacy was better when lacosamide was the first or second add-on AED, although there was a small chance to be seizure-free even for patients who had received ≤10 prior AEDs. The mechanism of action of concomitant AEDs is important in all the stages, but differences are smaller in the early stages. Lacosamide was generally well tolerated. A slower dosage-titration schedule was associated with a lower adverse event rate. Further investigation of the timing of initiation of lacosamide add-on therapy and ideal combinations of AEDs is required. © 2013.

  8. Reasons for uncontrolled seizures in adults; the impact of pseudointractability.

    PubMed

    Asadi-Pooya, Ali A; Emami, Mehrdad; Ashjazadeh, Nahid; Nikseresht, Alireza; Shariat, Abdolhamid; Petramfar, Peyman; Yousefipour, Gholamali; Borhani-Haghighi, Afshin; Izadi, Sadegh; Rahimi-Jaberi, Abbas

    2013-05-01

    We investigated the various possible reasons for uncontrolled seizures in patients 18 years of age and older to determine the impact of pseudointractability. We also tried to investigate the various forms of pseudointractability. In this cross-sectional study, all patients 18 years of age and older with their first seizure occurring at least six months prior to the referral date, taking at least one antiepileptic drug (AED) and having at least one seizure in the past three months were studied. The presumed reason for uncontrolled seizures was arbitrarily considered to be one of these five categories: Poor compliance; Wrong medication (misclassification); Wrong dose of the correct medication; Diagnosis other than epilepsy; and finally, Medically-refractory epilepsy. Statistical analyses were performed using Chi-square and Fisher's exact tests, and a P value less than 0.05 was considered significant. 350 patients were referred to us due to uncontrolled seizures. One hundred ninety-one (55%) were male and 159 (45%) were female. Twelve percent of the patients had diagnoses other than epilepsy, 40% had indeed medically-refractory epilepsy; 29% were taking the wrong AEDs (misclassified epilepsy); 18% were taking suboptimal doses of AEDs; and 1% had poor drug compliance. The most common reason for uncontrolled seizures among patients with idiopathic generalized epilepsy was taking the wrong AED. However, among patients with focal epilepsy, true medically-refractory epilepsy was the most common reason. Uncontrolled seizures are a commonly encountered problem, especially at epilepsy clinics and one should consider all possible reasons for these uncontrolled seizures. The mainstay for making a correct diagnosis is a detailed clinical history. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  9. The effect of dorsal hippocampal administration of nicotinic and muscarinic cholinergic ligands on pentylenetetrazol-induced generalized seizures in rats.

    PubMed

    Gholami, Morteza; Saboory, Ehsan; Zare, Samad; Roshan-Milani, Shiva; Hajizadeh-Moghaddam, Akbar

    2012-10-01

    In the present study, the effects of intrahippocampal injections of cholinergic ligands on pentylenetetrazol (PTZ)-induced seizures were investigated in rats. The rats were assigned to 1 of the following 9 groups: saline, nicotine (0.5 or 1 μg), atropine (0.25 or 1 μg), oxotremorine-M (0.1 or 1 μg), or mecamylamine (2 or 8 μg). Cholinergic ligands were administered via intrahippocampal infusion 30 min before seizure induction (intraperitoneal injection of 80 mg/kg PTZ). Results show that antagonists caused nonsignificant increases in the latency of tonic-clonic seizures, significant decreases in the duration of tonic-clonic seizures, significant decreases in the latency of death, and increases in mortality rate. Agonists led to increases in the duration of tonic-clonic seizures, decreases in the latency of death, and decreases in mortality rate. These results provide compelling evidence that cholinergic ligands show modulatory effects on a PTZ model of acute seizure in the rat hippocampus. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Sustained consumption of cocoa-based dark chocolate enhances seizure-like events in the mouse hippocampus.

    PubMed

    Cicvaric, Ana; Bulat, Tanja; Bormann, Daniel; Yang, Jiaye; Auer, Bastian; Milenkovic, Ivan; Cabatic, Maureen; Milicevic, Radoslav; Monje, Francisco J

    2018-03-01

    While the consumption of caffeine and cocoa has been associated with a variety of health benefits to humans, some authors have proposed that excessive caffeine intake may increase the frequency of epileptic seizures in humans and reduce the efficiency of antiepileptic drugs. Little is known, however, about the proconvulsant potential of the sustained, excessive intake of cocoa on hippocampal neural circuits. Using the mouse as an experimental model, we examined the effects of the chronic consumption of food enriched in cocoa-based dark chocolate on motor and mood-related behaviours as well as on the excitability properties of hippocampal neurons. Cocoa food enrichment did not affect body weights or mood-related behaviours but rather promoted general locomotion and improved motor coordination. However, ex vivo electrophysiological analysis revealed a significant enhancement in seizure-like population spike bursting at the neurogenic dentate gyrus, which was paralleled by a significant reduction in the levels of GABA-α1 receptors thus suggesting that an excessive dietary intake of cocoa-enriched food might alter some of the synaptic elements involved in epileptogenesis. These data invite further multidisciplinary research aiming to elucidate the potential deleterious effects of chocolate abuse on behaviour and brain hyperexcitability.

  11. Methamphetamine-induced neuronal necrosis: the role of electrographic seizure discharges

    PubMed Central

    Fujikawa, Denson G.; Pais, Emil S.; Aviles, Ernesto R.; Hsieh, Kung-Chiao; Bashir, Muhammad Tariq

    2016-01-01

    We have evidence that methamphetamine (METH)-induced neuronal death is morphologically necrotic, not apoptotic, as is currently believed, and that electrographic seizures may be responsible. We administered 40 mg/kg i.p. to 12 male C57BL/6 mice and monitored EEGs continuously and rectal temperatures every 15 min, keeping rectal temperatures <41.0 °C. Seven of the 12 mice had repetitive electrographic seizure discharges (RESDs) and 5 did not. The RESDs were often not accompanied by behavioral signs of seizures–i.e., they were often not accompanied by clonic forelimb movements. The 7 mice with RESDs had acidophilic neurons (the H&E light-microscopic equivalent of necrotic neurons by ultrastructural examination) in all of 7 brain regions (hippocampal CA1, CA2, CA3 and hilus, amygdala, piriform cortex and entorhinal cortex), the same brain regions damaged following generalized seizures, 24 h after METH administration. The 5 mice without RESDs had a few acidophilic neurons in 4 of the 7 brain regions, but those with RESDs had significantly more in 6 of the 7 brain regions. Maximum rectal temperatures were comparable in mice with and without RESDs, so that cannot explain the difference between the two groups with respect to METH-induced neuronal death. Our data show that METH-induced neuronal death is morphologically necrotic, that EEGs must be recorded to detect electrographic seizure activity in rodents without behavioral evidence of seizures, and that RESDs may be responsible for METH-induced neuronal death. PMID:26562800

  12. Mouse repeated electroconvulsive seizure (ECS) does not reverse social stress effects but does induce behavioral and hippocampal changes relevant to electroconvulsive therapy (ECT) side-effects in the treatment of depression

    PubMed Central

    Sigrist, Hannes; Seifritz, Erich; Fikse, Lianne; Bosker, Fokko J.; Schoevers, Robert A.; Klein, Hans C.

    2017-01-01

    Electroconvulsive therapy (ECT) is an effective treatment for depression, but can have negative side effects including amnesia. The mechanisms of action underlying both the antidepressant and side effects of ECT are not well understood. An equivalent manipulation that is conducted in experimental animals is electroconvulsive seizure (ECS). Rodent studies have provided valuable insights into potential mechanisms underlying the antidepressant and side effects of ECT. However, relatively few studies have investigated the effects of ECS in animal models with a depression-relevant manipulation such as chronic stress. In the present study, mice were first exposed to chronic social stress (CSS) or a control procedure for 15 days followed by ECS or a sham procedure for 10 days. Behavioral effects were investigated using an auditory fear conditioning (learning) and expression (memory) test and a treadmill-running fatigue test. Thereafter, immunohistochemistry was conducted on brain material using the microglial marker Iba-1 and the cholinergic fibre marker ChAT. CSS did not increase fear learning and memory in the present experimental design; in both the control and CSS mice ECS reduced fear learning and fear memory expression. CSS induced the expected fatigue-like effect in the treadmill-running test; ECS induced increased fatigue in CSS and control mice. In CSS and control mice ECS induced inflammation in hippocampus in terms of increased expression of Iba-1 in radiatum of CA1 and CA3. CSS and ECS both reduced acetylcholine function in hippocampus as indicated by decreased expression of ChAT in several hippocampal sub-regions. Therefore, CSS increased fatigue and reduced hippocampal ChAT activity and, rather than reversing these effects, a repeated ECS regimen resulted in impaired fear learning-memory, increased fatigue, increased hippocampal Iba-1 expression, and decreased hippocampal ChAT expression. As such, the current model does not provide insights into the

  13. Mouse repeated electroconvulsive seizure (ECS) does not reverse social stress effects but does induce behavioral and hippocampal changes relevant to electroconvulsive therapy (ECT) side-effects in the treatment of depression.

    PubMed

    van Buel, Erin M; Sigrist, Hannes; Seifritz, Erich; Fikse, Lianne; Bosker, Fokko J; Schoevers, Robert A; Klein, Hans C; Pryce, Christopher R; Eisel, Ulrich Lm

    2017-01-01

    Electroconvulsive therapy (ECT) is an effective treatment for depression, but can have negative side effects including amnesia. The mechanisms of action underlying both the antidepressant and side effects of ECT are not well understood. An equivalent manipulation that is conducted in experimental animals is electroconvulsive seizure (ECS). Rodent studies have provided valuable insights into potential mechanisms underlying the antidepressant and side effects of ECT. However, relatively few studies have investigated the effects of ECS in animal models with a depression-relevant manipulation such as chronic stress. In the present study, mice were first exposed to chronic social stress (CSS) or a control procedure for 15 days followed by ECS or a sham procedure for 10 days. Behavioral effects were investigated using an auditory fear conditioning (learning) and expression (memory) test and a treadmill-running fatigue test. Thereafter, immunohistochemistry was conducted on brain material using the microglial marker Iba-1 and the cholinergic fibre marker ChAT. CSS did not increase fear learning and memory in the present experimental design; in both the control and CSS mice ECS reduced fear learning and fear memory expression. CSS induced the expected fatigue-like effect in the treadmill-running test; ECS induced increased fatigue in CSS and control mice. In CSS and control mice ECS induced inflammation in hippocampus in terms of increased expression of Iba-1 in radiatum of CA1 and CA3. CSS and ECS both reduced acetylcholine function in hippocampus as indicated by decreased expression of ChAT in several hippocampal sub-regions. Therefore, CSS increased fatigue and reduced hippocampal ChAT activity and, rather than reversing these effects, a repeated ECS regimen resulted in impaired fear learning-memory, increased fatigue, increased hippocampal Iba-1 expression, and decreased hippocampal ChAT expression. As such, the current model does not provide insights into the

  14. Long-term neuropsychological, neuroanatomical, and life outcome in hippocampal amnesia

    PubMed Central

    Warren, David E.; Duff, Melissa C.; Magnotta, Vincent; Capizzano, Aristides A; Cassell, Martin D.; Tranel, Daniel

    2012-01-01

    Focal bilateral hippocampal damage typically causes severe and selective amnesia for new declarative information (facts and events), a cognitive deficit that greatly impacts the ability to live a normal, fully-independent life. We describe the case of 1846, a 48-year-old woman with profound hippocampal amnesia following status epilepticus and an associated anoxic episode at age 30. 1846 has undergone extensive neuropsychological testing on many occasions over the 18 years since her injury, and we present data indicating that her memory impairment has remained severe and stable during that time. New, high-resolution structural MRI studies of 1846's brain reveal substantial bilateral hippocampal atrophy resembling that of other well-known amnesic patients. In spite of severe amnesia, 1846 lives a full and mostly independent adult life, facilitated by an extensive social support network of family and friends. Her case provides an example of a rare and unlikely positive outcome in the face of severe memory problems. PMID:22401298

  15. Seizure entrainment with polarizing low frequency electric fields in a chronic animal epilepsy model

    PubMed Central

    Sunderam, Sridhar; Chernyy, Nick; Peixoto, Nathalia; Mason, Jonathan P.; Weinstein, Steven L.; Schiff, Steven J.; Gluckman, Bruce J.

    2009-01-01

    Neural activity can be modulated by applying a polarizing low frequency (≪ 100 Hz) electric field (PLEF). Unlike conventional pulsed stimulation, PLEF stimulation has a graded, modulatory effect on neuronal excitability, and permits the simultaneous recording of neuronal activity during stimulation suitable for continuous feedback control. We tested a prototype system that allows for simultaneous PLEF stimulation with minimal recording artifact in a chronic tetanus toxin animal model (rat) of hippocampal epilepsy with spontaneous seizures. Depth electrode local field potentials recorded during seizures revealed a characteristic pattern of field postsynaptic potentials (fPSPs). Sinusoidal voltage-controlled PLEF stimulation (0.5–25 Hz) was applied in open-loop cycles radially across the CA3 of ventral hippocampus. For stimulated seizures, fPSPs were transiently entrained with the PLEF waveform. Statistical significance of entrainment was assessed with Thomson’s harmonic F-test, with 45/132 stimulated seizures in 4 animals individually demonstrating significant entrainment (p < 0.04). Significant entrainment for multiple presentations at the same frequency (p < 0.01) was observed in 3 of 4 animals in 42/64 stimulated seizures. This is the first demonstration in chronically implanted freely behaving animals of PLEF modulation of neural activity with simultaneous recording. PMID:19602730

  16. BID Mediates Oxygen-Glucose Deprivation-Induced Neuronal Injury in Organotypic Hippocampal Slice Cultures and Modulates Tissue Inflammation in a Transient Focal Cerebral Ischemia Model without Changing Lesion Volume

    PubMed Central

    Martin, Nellie Anne; Bonner, Helena; Elkjær, Maria Louise; D’Orsi, Beatrice; Chen, Gang; König, Hans Georg; Svensson, Martina; Deierborg, Tomas; Pfeiffer, Shona; Prehn, Jochen H.; Lambertsen, Kate Lykke

    2016-01-01

    The BH3 interacting-domain death agonist (BID) is a pro-apoptotic protein involved in death receptor-induced and mitochondria-mediated apoptosis. Recently, it has also been suggested that BID is involved in the regulation of inflammatory responses in the central nervous system. We found that BID deficiency protected organotypic hippocampal slice cultures in vitro from neuronal injury induced by oxygen-glucose deprivation. In vivo, BID-knockout (KO) mice and wild type (WT) mice were subjected to 60 min of transient middle cerebral artery occlusion (tMCAO) to induce focal cerebral ischemia, and allowed to recover for 24 h. Infarct volumes and functional outcome were assessed and the inflammatory response was evaluated using immunofluorescence, Western blotting, quantitative PCR (qPCR) and Mesoscale multiplex analysis. We observed no difference in the infarct volume or neurological outcome between BID-KO and WT mice. The inflammatory response was reduced by BID deficiency as indicated by a change in microglial/leukocyte response. In conclusion, our data suggest that BID deficiency is neuroprotective in an in vitro model and modulates the inflammatory response to focal cerebral ischemia in vivo. However, this is not translated into a robust neuroprotection in vivo. PMID:26869884

  17. Faciobrachial dystonic seizures: the influence of immunotherapy on seizure control and prevention of cognitive impairment in a broadening phenotype.

    PubMed

    Irani, Sarosh R; Stagg, Charlotte J; Schott, Jonathan M; Rosenthal, Clive R; Schneider, Susanne A; Pettingill, Philippa; Pettingill, Rosemary; Waters, Patrick; Thomas, Adam; Voets, Natalie L; Cardoso, Manuel J; Cash, David M; Manning, Emily N; Lang, Bethan; Smith, Shelagh J M; Vincent, Angela; Johnson, Michael R

    2013-10-01

    months in six cases. Voltage-gated potassium channel-complex antibodies persisted in the four cases with relapses of faciobrachial dystonic seizures during corticosteroid withdrawal. Time to recovery of baseline function was positively correlated with time to immunotherapy (r = 0.74; P = 0.03) but not time to anti-epileptic drug administration (r = 0.55; P = 0.10). Of 10 cases, the eight cases who received anti-epileptic drugs (n = 3) or no treatment (n = 5) all developed cognitive impairment. By contrast, the two who did not develop cognitive impairment received immunotherapy to treat their faciobrachial dystonic seizures (P = 0.02). In eight cases without clinical magnetic resonance imaging evidence of hippocampal signal change, cross-sectional volumetric magnetic resonance imaging post-recovery, after accounting for age and head size, revealed cases (n = 8) had smaller brain volumes than healthy controls (n = 13) (P < 0.001). In conclusion, faciobrachial dystonic seizures can be prospectively identified as a form of epilepsy with an expanding phenotype. Immunotherapy is associated with excellent control of the frequently anti-epileptic drug refractory seizures, hastens time to recovery, and may prevent the subsequent development of cognitive impairment observed in this study.

  18. The effect of albendazole treatment on seizure outcomes in patients with symptomatic neurocysticercosis.

    PubMed

    Romo, Matthew L; Wyka, Katarzyna; Carpio, Arturo; Leslie, Denise; Andrews, Howard; Bagiella, Emilia; Hauser, W Allen; Kelvin, Elizabeth A

    2015-11-01

    Randomized controlled trials have found an inconsistent effect of anthelmintic treatment on long-term seizure outcomes in neurocysticercosis. The objective of this study was to further explore the effect of albendazole treatment on long-term seizure outcomes and to determine if there is evidence for a differential effect by seizure type. In this trial, 178 patients with active or transitional neurocysticercosis cysts and new-onset symptoms were randomized to 8 days of treatment with albendazole (n=88) or placebo (n=90), both with prednisone, and followed for 24 months. We used negative binomial regression and logistic regression models to determine the effect of albendazole on the number of seizures and probability of recurrent or new-onset seizures, respectively, over follow-up. Treatment with albendazole was associated with a reduction in the number of seizures during 24 months of follow-up, but this was only significant for generalized seizures during months 1-12 (unadjusted rate ratio [RR] 0.19; 95% CI: 0.04-0.91) and months 1-24 (unadjusted RR 0.06; 95% CI: 0.01-0.57). We did not detect a significant effect of albendazole on reducing the number of focal seizures or on the probability of having a seizure, regardless of seizure type or time period. Albendazole treatment may be associated with some symptomatic improvement; however, this association seems to be specific to generalized seizures. Future research is needed to identify strategies to better reduce long-term seizure burden in patients with neurocysticercosis. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. Targeted Interneuron Ablation in the Mouse Hippocampus Can Cause Spontaneous Recurrent Seizures

    PubMed Central

    2017-01-01

    Abstract The death of GABAergic interneurons has long been hypothesized to contribute to acquired epilepsy. These experiments tested the hypothesis that focal interneuron lesions cause acute seizures [i.e., status epilepticus (SE)] and/or chronic epilepsy [i.e., persistent spontaneous recurrent seizures (SRSs)]. To selectively ablate interneurons, Gad2-ires-Cre mice were injected unilaterally in the CA1 area of the dorsal hippocampus with an adeno-associated virus containing the diphtheria toxin receptor (DTR). Simultaneously, an electrode, connected to a miniature telemetry device, was positioned at the injection site for chronic recordings of local field potentials (LFPs). Two weeks after virus transfection, intraperitoneal injection of DT consistently caused focal, specific, and extensive ablation of interneurons. Long-term, continuous monitoring revealed that all mice with DT-induced interneuron lesions had SRSs. Seizures lasted tens of seconds and interseizure intervals were several hours (or days); therefore, these interneuron lesions did not induce SE. The SRSs occurred 3-5 d after DT treatment, which is the estimated time required for DT-induced cell death; therefore, induction of SRSs occurred without the latent period typical of acquired epilepsy. In five of six DT-treated mice, SRSs stopped within days, suggesting that the DT-induced interneuron lesions did not usually cause epilepsy. In one mouse, however, SRSs occurred for ≥34 d after interneuron ablation, similar to epilepsy after experimental SE. Sham control mice had no detectable seizures, confirming that the SRSs were due to ablation of interneurons. These data show that selective interneuron ablation consistently caused SRSs but not SE; and, at least under the conditions used here, interneuron lesions rarely led to persistent SRSs (i.e., epilepsy). PMID:28785726

  20. Cardiac arrhythmias during or after epileptic seizures

    PubMed Central

    van der Lende, Marije; Surges, Rainer; Sander, Josemir W; Thijs, Roland D

    2016-01-01

    Seizure-related cardiac arrhythmias are frequently reported and have been implicated as potential pathomechanisms of Sudden Unexpected Death in Epilepsy (SUDEP). We attempted to identify clinical profiles associated with various (post)ictal cardiac arrhythmias. We conducted a systematic search from the first date available to July 2013 on the combination of two terms: ‘cardiac arrhythmias’ and ‘epilepsy’. The databases searched were PubMed, Embase (OVID version), Web of Science and COCHRANE Library. We attempted to identify all case reports and case series. We identified seven distinct patterns of (post)ictal cardiac arrhythmias: ictal asystole (103 cases), postictal asystole (13 cases), ictal bradycardia (25 cases), ictal atrioventricular (AV)-conduction block (11 cases), postictal AV-conduction block (2 cases), (post)ictal atrial flutter/atrial fibrillation (14 cases) and postictal ventricular fibrillation (3 cases). Ictal asystole had a mean prevalence of 0.318% (95% CI 0.316% to 0.320%) in people with refractory epilepsy who underwent video-EEG monitoring. Ictal asystole, bradycardia and AV-conduction block were self-limiting in all but one of the cases and seen during focal dyscognitive seizures. Seizure onset was mostly temporal (91%) without consistent lateralisation. Postictal arrhythmias were mostly found following convulsive seizures and often associated with (near) SUDEP. The contrasting clinical profiles of ictal and postictal arrhythmias suggest different pathomechanisms. Postictal rather than ictal arrhythmias seem of greater importance to the pathophysiology of SUDEP. PMID:26038597

  1. Temporal lobe epilepsy in a cat with a pyriform lobe oligodendroglioma and hippocampal necrosis.

    PubMed

    Vanhaesebrouck, An E; Posch, Barbara; Baker, Sam; Plessas, Ioannis N; Palmer, Anthony C; Constantino-Casas, Fernando

    2012-12-01

    A 14-year-old male domestic shorthair cat presented with an acute onset of aggressive behaviour, fear and hypersalivation. Neurological examination revealed bilateral mydriasis and left-sided facial twitching and hemiparesis. Magnetic resonance imaging (MRI) showed moderate bilateral symmetrical T2-hyperintensity along the entire hippocampus and bilateral asymmetric T2-hyperintensity in the pyriform lobes. Marked bilateral contrast enhancement of the hippocampus was evident on post-contrast T1-weighted images. The partial complex seizures were refractory to medical treatment and the cat was euthanased 4 days after admission. The clinical and MRI findings were consistent with feline hippocampal necrosis (FHN). On histopathology, neuronal necrosis and astrocytosis were present in the hippocampi and pyriform lobes. In addition, an oligodendroglioma was detected in the right pyriform lobe. Contrary to previous reports of FHN in which no underlying cause could be identified, we believe that in this case the seizure focus arose from a neoplastic lesion within the right pyriform lobe. This unique case report represents the so-called 'dual pathology' of temporal lobe epilepsy in humans, in which an extrahippocampal lesion within the temporal lobe results in hippocampal sclerosis.

  2. Interictal and Postictal Performances on Dichotic Listening Test in Children with Focal Epilepsy

    ERIC Educational Resources Information Center

    Carlsson, G.; Wiegand, G.; Stephani, U.

    2011-01-01

    Dichotic listening test (DL) is an important tool to disclose speech dominance in healthy subjects and in clinical cases. The aim of this study was to probe if focal epilepsy in children reveals a corresponding suppression of the ear reports contralateral to seizure onset site. Thus, 15 children and adolescents with clinically and…

  3. Ictal semiology in hippocampal versus extrahippocampal temporal lobe epilepsy.

    PubMed

    Gil-Nagel, A; Risinger, M W

    1997-01-01

    We have analysed retrospectively the clinical features and electroencephalograms in 35 patients with complex partial seizures of temporal lobe origin who were seizure-free after epilepsy surgery. Two groups were differentiated for statistical analysis: 16 patients had hippocampal temporal lobe seizures (HTS) and 19 patients had extrahippocampal temporal lobe seizures (ETS) associated with a small tumour of the lateral or inferior temporal cortex. All patients in the HTS group had ictal onset verified with intracranial recordings (depth or subdural electrodes). In the ETS group, extrahippocampal onset was verified with intracranial recordings in eight patients and assumed, because of failure of a previous amygdalohippocampectomy, in one patient. Historical information, ictal semiology and ictal EEG of typical seizures were analysed in each patient. The occurrence of early and late oral automatisms and dystonic posturing of an upper extremity was analysed separately. A prior history of febrile convulsions was obtained in 13 HTS patients (81.3%) but in none with ETS (P < 0.0001, Fisher's exact test). An epigastric aura preceded seizures in five patients with HTS (31.3%) and none with ETS (P = 0.0135, Fisher's exact test), while an aura with experiential content was recalled by nine patients with ETS (47.4%) and none with HTS (P = 0.0015), Fisher's exact test). Early oral automatisms occurred in 11 patients with HTS (68.8%) and in two with ETS (10.5%) (P = 0.0005, Fisher's exact test). Early motor involvement of the contralateral upper extremity without oral automatisms occurred in three patients with HTS (18.8%) and in 10 with ETS (52.6%) (P = 0.0298, Fisher's exact test). Arrest reaction, vocalization, speech, facial grimace, postictal cough, late oral automatisms and late motor involvement of the contralateral arm and hand occurred with similar frequency in both groups. These observations show that the early clinical features of HTS and ETS are different.

  4. Clinical Profile and Electroencephalogram Findings in Children with Seizure Presenting to Dhulikhel Hospital.

    PubMed

    Poudyal, P; Shrestha, R Pb; Shrestha, P S; Dangol, S; Shrestha, N C; Joshi, A; Shrestha, A

    Background Seizure disorder is the most common childhood neurologic condition and a major public health concern. Identification of the underlying seizure etiology helps to identify appropriate treatment options and the prognosis for the child. Objective This study was conducted to investigate the clinical profile, causes and electroencephalogram findings in children with seizure presenting to a tertiary center in Kavre district. Method This was a hospital based prospective study carried out in the Department of Pediatrics, Dhulikhel Hospital, Kavre from 1st April 2015 to 31st March 2016. Variables collected were demographics, clinical presentations, laboratory tests, brain imaging studies, electroencephalography, diagnosis and outcome. Result Study included 120 (age 1 month to 16 years) children attending Dhulikhel Hospital. Majority of the patients were male (60.84%). Age at first seizure was less than 5 years in 75.83% of children. Seizure was generalized in 62.50%, focal in 31.67% and unclassified in 5.83%. Common causes of seizure were - Primary generalized epilepsy (26.66%), neurocysticercosis (10%) and hypoxic injury (6.6%) which was diagnosed in the perinatal period. Febrile seizure (26.66%) was the most common cause of seizure in children between 6 months to 5 years of age. Neurological examination, electroencephalography and Computed Tomography were abnormal in 71.66%, 68.92% and 58.14% cases respectively. Seizure was controlled by monotherapy in 69.16% cases and was resistant in 7.50% of the cases. Conclusion Primary generalized epilepsy and febrile seizure were the most common causes of seizures in children attending Dhulikhel Hospital. Electroencephalogram findings help to know the pattern of neuronal activity. Response to monotherapy was good and valproic acid was the most commonly used drug.

  5. Seizure classification key to epilepsy management.

    PubMed

    Davidson, Louise; Derry, Chris

    2015-09-01

    The diagnosis of epilepsy carries significant implications for physical, psychosocial and financial wellbeing as well as a small but significant increased risk of mortality. The diagnosis is often incorrect, potentially in up to 20% of cases, so should be revisited if seizures are not responding to treatment. Evidence indicates that misdiagnosis is significantly more common among nonspecialists. SIGN recommends that the diagnosis of epilepsy should be made by an epilepsy specialist, ideally in the setting of a dedicated first seizure or epilepsy clinic. An incorrect diagnosis of epilepsy can be harmful. There is an exhaustive list of epilepsy mimics that can result in misdiagnosis and expose patients to unnecessary treatment with antiepileptic drugs. Diagnosis relies primarily on the history. Investigations can support the diagnosis but cannot make it in isolation, and negative investigation findings are common in epilepsy. Brain imaging will be undertaken in most patients with epilepsy, but is not routinely required in those with a definite diagnosis of genetic generalised epilepsy. The EEG has limitations and can sometimes cloud rather than clarify the diagnostic picture. Distinguishing between a genetic generalised epilepsy and a focal epilepsy is vital as this influences investigation, treatment and prognosis. Generally medication should not be started following a single seizure except in specific circumstances or in cases where the risk of recurrence is high.

  6. Assessment of the usefulness of magnetic resonance brain imaging in patients presenting with acute seizures.

    PubMed

    Olszewska, D A; Costello, D J

    2014-12-01

    Magnetic Resonance Imaging (MRI) is increasingly available as a tool for assessment of patients presenting to acute services with seizures. We set out to prospectively determine the usefulness of early MRI brain in a cohort of patients presenting with acute seizures. We examined the MR imaging studies performed in patients admitted solely because of acute seizures to Cork University Hospital over a 12-month period. The main aim of the study was to determine if the MRI established the proximate cause for the patient's recent seizure. We identified 91 patients who underwent MRI brain within 48 h of admission for seizures. Of the 91 studies, 51 were normal (56 %). The remaining 40 studies were abnormal as follows: microvascular disease (usually moderate/severe) (n = 19), post-traumatic gliosis (n = 7), remote symptomatic lesion (n = 6), primary brain tumour (n = 5), venous sinus thrombosis (n = 3), developmental lesion (n = 3), post-surgical gliosis (n = 3) and single cases of demyelination, unilateral hippocampal sclerosis, lobar haemorrhage and metastatic malignant melanoma. Abnormalities in diffusion-weighted sequences that were attributable to prolonged ictal activity were seen in nine patients, all of who had significant ongoing clinical deficits, most commonly delirium. Of the 40 patients with abnormal MRI studies, seven patients had unremarkable CT brain. MR brain imaging revealed the underlying cause for acute seizures in 44 % of patients. CT brain imaging failed to detect the cause of the acute seizures in 19 % of patients in whom subsequent MRI established the cause. This study emphasises the importance of obtaining optimal imaging in people admitted with acute seizures.

  7. Temporal lobe epilepsy: quantitative MR volumetry in detection of hippocampal atrophy.

    PubMed

    Farid, Nikdokht; Girard, Holly M; Kemmotsu, Nobuko; Smith, Michael E; Magda, Sebastian W; Lim, Wei Y; Lee, Roland R; McDonald, Carrie R

    2012-08-01

    To determine the ability of fully automated volumetric magnetic resonance (MR) imaging to depict hippocampal atrophy (HA) and to help correctly lateralize the seizure focus in patients with temporal lobe epilepsy (TLE). This study was conducted with institutional review board approval and in compliance with HIPAA regulations. Volumetric MR imaging data were analyzed for 34 patients with TLE and 116 control subjects. Structural volumes were calculated by using U.S. Food and Drug Administration-cleared software for automated quantitative MR imaging analysis (NeuroQuant). Results of quantitative MR imaging were compared with visual detection of atrophy, and, when available, with histologic specimens. Receiver operating characteristic analyses were performed to determine the optimal sensitivity and specificity of quantitative MR imaging for detecting HA and asymmetry. A linear classifier with cross validation was used to estimate the ability of quantitative MR imaging to help lateralize the seizure focus. Quantitative MR imaging-derived hippocampal asymmetries discriminated patients with TLE from control subjects with high sensitivity (86.7%-89.5%) and specificity (92.2%-94.1%). When a linear classifier was used to discriminate left versus right TLE, hippocampal asymmetry achieved 94% classification accuracy. Volumetric asymmetries of other subcortical structures did not improve classification. Compared with invasive video electroencephalographic recordings, lateralization accuracy was 88% with quantitative MR imaging and 85% with visual inspection of volumetric MR imaging studies but only 76% with visual inspection of clinical MR imaging studies. Quantitative MR imaging can depict the presence and laterality of HA in TLE with accuracy rates that may exceed those achieved with visual inspection of clinical MR imaging studies. Thus, quantitative MR imaging may enhance standard visual analysis, providing a useful and viable means for translating volumetric analysis into

  8. Hippocampal Network Modularity Is Associated With Relational Memory Dysfunction in Schizophrenia.

    PubMed

    Avery, Suzanne N; Rogers, Baxter P; Heckers, Stephan

    2018-05-01

    Functional dysconnectivity has been proposed as a major pathophysiological mechanism for cognitive dysfunction in schizophrenia. The hippocampus is a focal point of dysconnectivity in schizophrenia, with decreased hippocampal functional connectivity contributing to the marked memory deficits observed in patients. Normal memory function relies on the interaction of complex corticohippocampal networks. However, only recent technological advances have enabled the large-scale exploration of functional networks with accuracy and precision. We investigated the modularity of hippocampal resting-state functional networks in a sample of 45 patients with schizophrenia spectrum disorders and 38 healthy control subjects. Modularity was calculated for two distinct functional networks: a core hippocampal-medial temporal lobe cortex network and an extended hippocampal-cortical network. As hippocampal function differs along its longitudinal axis, follow-up analyses examined anterior and posterior networks separately. To explore effects of resting network function on behavior, we tested associations between modularity and relational memory ability. Age, sex, handedness, and parental education were similar between groups. Network modularity was lower in schizophrenia patients, especially in the posterior hippocampal network. Schizophrenia patients also showed markedly lower relational memory ability compared with control subjects. We found a distinct brain-behavior relationship in schizophrenia that differed from control subjects by network and anterior/posterior division-while relational memory in control subjects was associated with anterior hippocampal-cortical modularity, schizophrenia patients showed an association with posterior hippocampal-medial temporal lobe cortex network modularity. Our findings support a model of abnormal resting-state corticohippocampal network coherence in schizophrenia, which may contribute to relational memory deficits. Copyright © 2018 Society of

  9. Seizures in the elderly: development and validation of a diagnostic algorithm.

    PubMed

    Dupont, Sophie; Verny, Marc; Harston, Sandrine; Cartz-Piver, Leslie; Schück, Stéphane; Martin, Jennifer; Puisieux, François; Alecu, Cosmin; Vespignani, Hervé; Marchal, Cécile; Derambure, Philippe

    2010-05-01

    Seizures are frequent in the elderly, but their diagnosis can be challenging. The objective of this work was to develop and validate an expert-based algorithm for the diagnosis of seizures in elderly people. A multidisciplinary group of neurologists and geriatricians developed a diagnostic algorithm using a combination of selected clinical, electroencephalographical and radiological criteria. The algorithm was validated by multicentre retrospective analysis of data of patients referred for specific symptoms and classified by the experts as epileptic patients or not. The algorithm was applied to all the patients, and the diagnosis provided by the algorithm was compared to the clinical diagnosis of the experts. Twenty-nine clinical, electroencephalographical and radiological criteria were selected for the algorithm. According to criteria combination, seizures were classified in four levels of diagnosis: certain, highly probable, possible or improbable. To validate the algorithm, the medical records of 269 elderly patients were analyzed (138 with epileptic seizures, 131 with non-epileptic manifestations). Patients were mainly referred for a transient focal deficit (40%), confusion (38%), unconsciousness (27%). The algorithm best classified certain and probable seizures versus possible and improbable seizures, with 86.2% sensitivity and 67.2% specificity. Using logistical regression, 2 simplified models were developed, the first with 13 criteria (Se 85.5%, Sp 90.1%), and the second with 7 criteria only (Se 84.8%, Sp 88.6%). In conclusion, the present study validated the use of a revised diagnostic algorithm to help diagnosis epileptic seizures in the elderly. A prospective study is planned to further validate this algorithm. Copyright 2010 Elsevier B.V. All rights reserved.

  10. The role of executive functioning in memory performance in pediatric focal epilepsy.

    PubMed

    Sepeta, Leigh N; Casaletto, Kaitlin Blackstone; Terwilliger, Virginia; Facella-Ervolini, Joy; Sady, Maegan; Mayo, Jessica; Gaillard, William D; Berl, Madison M

    2017-02-01

    Learning and memory are essential for academic success and everyday functioning, but the pattern of memory skills and its relationship to executive functioning in children with focal epilepsy is not fully delineated. We address a gap in the literature by examining the relationship between memory and executive functioning in a pediatric focal epilepsy population. Seventy children with focal epilepsy and 70 typically developing children matched on age, intellectual functioning, and gender underwent neuropsychological assessment, including measures of intelligence (Wechsler Abbreviated Scale of Intelligence [WASI]/Differential Ability Scales [DAS]), as well as visual Children's Memory Scale (CMS Dot Locations) and verbal episodic memory (Wide Range Assessment of Memory and Learning [WRAML] Story Memory and California Verbal Learning Test for Children [CVLT-C]). Executive functioning was measured directly (WISC-IV Digit Span Backward; Clinical Evaluation of Language Fundamentals, Fourth Edition (CELF-IV) Recalling Sentences) and by parent report (Behavior Rating Inventory of Executive Function [BRIEF]). Children with focal epilepsy had lower delayed free-recall scores than controls across visual and verbal memory tasks (p = 0.02; partial η 2 = 0.12). In contrast, recognition memory performance was similar for patients and controls (p = 0.36; partial η 2 = 0.03). Children with focal epilepsy demonstrated difficulties in working memory (p = 0.02; partial η 2 = 0.08) and planning/organization (p = 0.02) compared to controls. Working memory predicted 9-19% of the variance in delayed free recall for verbal and visual memory; organization predicted 9-10% of the variance in verbal memory. Patients with both left and right focal epilepsy demonstrated more difficulty on verbal versus visual tasks (p = 0.002). Memory performance did not differ by location of seizure foci (temporal vs. extratemporal, frontal vs. extrafrontal). Children with focal epilepsy demonstrated memory

  11. Wortmannin Attenuates Seizure-Induced Hyperactive PI3K/Akt/mTOR Signaling, Impaired Memory, and Spine Dysmorphology in Rats

    PubMed Central

    Carter, Angela N.; Born, Heather A.; Levine, Amber T.; Dao, An T.; Zhao, Amanda J.; Lee, Wai L.

    2017-01-01

    Numerous studies have shown epilepsy-associated cognitive deficits, but less is known about the effects of one single generalized seizure. Recent studies demonstrate that a single, self-limited seizure can result in memory deficits and induces hyperactive phosphoinositide 3-kinase/Akt (protein kinase B)/mechanistic target of rapamycin (PI3K/Akt/mTOR) signaling. However, the effect of a single seizure on subcellular structures such as dendritic spines and the role of aberrant PI3K/Akt/mTOR signaling in these seizure-induced changes are unclear. Using the pentylenetetrazole (PTZ) model, we induced a single generalized seizure in rats and: (1) further characterized short- and long-term hippocampal and amygdala-dependent memory deficits, (2) evaluated whether there are changes in dendritic spines, and (3) determined whether inhibiting hyperactive PI3K/Akt/mTOR signaling rescued these alterations. Using the PI3K inhibitor wortmannin (Wort), we partially rescued short- and long-term memory deficits and altered spine morphology. These studies provide evidence that pathological PI3K/Akt/mTOR signaling plays a role in seizure-induced memory deficits as well as aberrant spine morphology. PMID:28612047

  12. Clinical outcome of recurrent afebrile seizures in children with benign convulsions associated with mild gastroenteritis.

    PubMed

    Chen, Boman; Cheng, Min; Hong, Siqi; Liao, Shuang; Ma, Jiannan; Li, Tingsong; Jiang, Li

    2018-05-30

    To assess the clinical outcome and evolution of recurrent afebrile seizures in children initially diagnosed with benign convulsions associated with mild gastroenteritis (CwG). We reviewed and analyzed the medical records of 37 patients who were diagnosed as CwG at onset, followed by recurrent afebrile seizures and followed up for at least 24 months. The follow-up period ranged from 2 to 7 years (median, 40.1 months).Three patterns of recurrent afebrile seizures were recorded: afebrile seizures associated with gastrointestinal infection (AS-GI, n = 25), afebrile seizures associated with non-gastrointestinal infection (AS-nGI, n = 9), and unprovoked seizures (US, n = 3). Twenty eight patients (75.7%) had a second episode within 6 months after the first seizures. Five cases (13.5%) suffered three episodes of afebrile seizures. Seizure characteristics of the three patterns were similar, manifesting as clustered seizures in the majority. Focal epileptic activities in interictal EEG were found in 3 cases (9.4%) at onset, 10 cases (28.6%) at the second episode, respectively. Six patients were prescribed anti-epileptic drugs with apparently good responses. During at least 2 years' follow-up, all the cases showed normal psychomotor development. Only one patient was diagnosed with epilepsy. All the recurrent afebrile seizures initially diagnosed as CwG, irrespective of the kinds and frequency of relapses, showed favorable prognoses. CwG maybe falls within the category of situation-related seizures, rather than epilepsy. Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  13. The performance of the spatiotemporal Kalman filter and LORETA in seizure onset localization.

    PubMed

    Hamid, Laith; Sarabi, Masoud; Japaridze, Natia; Wiegand, Gert; Heute, Ulrich; Stephani, Ulrich; Galka, Andreas; Siniatchkin, Michael

    2015-08-01

    The assumption of spatial-smoothness is often used to solve the bioelectric inverse problem during electroencephalographic (EEG) source imaging, e.g., in low resolution electromagnetic tomography (LORETA). Since the EEG data show a temporal structure, the combination of the temporal-smoothness and the spatial-smoothness constraints may improve the solution of the EEG inverse problem. This study investigates the performance of the spatiotemporal Kalman filter (STKF) method, which is based on spatial and temporal smoothness, in the localization of a focal seizure's onset and compares its results to those of LORETA. The main finding of the study was that the STKF with an autoregressive model of order two significantly outperformed LORETA in the accuracy and consistency of the localization, provided that the source space consists of a whole-brain volumetric grid. In the future, these promising results will be confirmed using data from more patients and performing statistical analyses on the results. Furthermore, the effects of the temporal smoothness constraint will be studied using different types of focal seizures.

  14. Converging PET and fMRI evidence for a common area involved in human focal epilepsies

    PubMed Central

    Laufs, H.; Richardson, M.P.; Salek-Haddadi, A.; Vollmar, C.; Duncan, J.S.; Gale, K.; Lemieux, L.; Löscher, W.

    2011-01-01

    Objectives: Experiments in animal models have identified specific subcortical anatomic circuits, which are critically involved in the pathogenesis and control of seizure activity. However, whether such anatomic substrates also exist in human epilepsy is not known. Methods: We studied 2 separate groups of patients with focal epilepsies arising from any cortical location using either simultaneous EEG-fMRI (n = 19 patients) or [11C]flumazenil PET (n = 18). Results: Time-locked with the interictal epileptiform discharges, we found significant hemodynamic increases common to all patients near the frontal piriform cortex ipsilateral to the presumed cortical focus. GABAA receptor binding in the same area was reduced in patients with more frequent seizures. Conclusions: Our findings of cerebral blood flow and GABAergic changes, irrespective of where interictal or ictal activity occurs in the cortex, suggest that this area of the human primary olfactory cortex may be an attractive new target for epilepsy therapy, including neurosurgery, electrical stimulation, and focal drug delivery. PMID:21849655

  15. Seizure semiology and electroencephalography in young children with lesional temporal lobe epilepsy.

    PubMed

    Lv, Rui-Juan; Sun, Zhen-Rong; Cui, Tao; Shao, Xiao-Qiu

    2014-02-01

    This study aimed to discuss the clinical features of seizure semiology and electroencephalography (EEG) in young children with lesional temporal lobe epilepsy (TLE). Children with lesional TLE received presurgical evaluation for intractable epilepsy. They were followed up for more than one year after temporal lobectomy. We reviewed the medical history and video-EEG monitoring of children with TLE to analyze the semiology of seizures and EEG findings and compared the semiology of seizures and EEG findings of childhood TLE and adult TLE. A total of 84 seizures were analyzed in 11 children (aged 23-108 months). The age of seizure onset was from 1 month to 26 months (a mean of 17.6 months). All of the patients exhibited prominent motor manifestations including epileptic spasm, tonic seizure, and unilateral clonic seizure. Seven children manifested behavioral arrest similar to an automotor seizure in adult TLE but with a shorter duration and higher frequency. The automatisms were typically orofacial, whereas manual automatisms were rarely observed. The EEG recordings revealed that diffuse discharge patterns were more common in younger children, whereas focal or unilateral patterns were more typical in older children. All of the patients were seizure-free after temporal lobectomy with more than one-year follow-up. All of the children had a mental development delay or regression; however, there was improvement after surgery, especially in those with surgery performed early. In contrast to TLE in adults, young children with lesional TLE probably represent a distinct nosological and probably less homogeneous syndrome. Although they had generalized clinical and electrographic features, resective epilepsy surgery should be considered as early as possible to obtain seizure control and improvement in mental development. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  16. Genetics of reflex seizures and epilepsies in humans and animals.

    PubMed

    Italiano, Domenico; Striano, Pasquale; Russo, Emilio; Leo, Antonio; Spina, Edoardo; Zara, Federico; Striano, Salvatore; Gambardella, Antonio; Labate, Angelo; Gasparini, Sara; Lamberti, Marco; De Sarro, Giovambattista; Aguglia, Umberto; Ferlazzo, Edoardo

    2016-03-01

    Reflex seizures are epileptic events triggered by specific motor, sensory or cognitive stimulation. This comprehensive narrative review focuses on the role of genetic determinants in humans and animal models of reflex seizures and epilepsies. References were mainly identified through MEDLINE searches until August 2015 and backtracking of references in pertinent studies. Autosomal dominant inheritance with reduced penetrance was proven in several families with photosensitivity. Molecular genetic studies on EEG photoparoxysmal response identified putative loci on chromosomes 6, 7, 13 and 16 that seem to correlate with peculiar seizure phenotype. No specific mutation has been found in Papio papio baboon, although a genetic etiology is likely. Mutation in synaptic vesicle glycoprotein 2A was found in another animal model of photosensitivity (Fayoumi chickens). Autosomal dominant inheritance with incomplete penetrance overlapping with a genetic background for IGE was proposed for some families with primary reading epilepsy. Musicogenic seizures usually occur in patients with focal symptomatic or cryptogenic epilepsies, but they have been reported in rare genetic epilepsies such as Dravet syndrome. A single LGI1 mutation has been described in a girl with seizures evoked by auditory stimuli. Interestingly, heterozygous knockout (Lgi1(+/-)) mice show susceptibility to sound-triggered seizures. Moreover, in Frings and Black Swiss mice, the spontaneous mutations of MASS1 and JAMS1 genes, respectively, have been linked to audiogenic seizures. Eating seizures usually occur in symptomatic epilepsies but evidences for a genetic susceptibility were mainly provided by family report from Sri Lanka. Eating seizures were also reported in rare patients with MECP2 duplication or mutation. Hot water seizures are genetically heterogeneous but two loci at chromosomes 4 and 10 were identified in families with likely autosomal dominant inheritance. Startle-induced seizures usually occur in

  17. Feasibility of recording high frequency oscillations with tripolar concentric ring electrodes during pentylenetetrazole-induced seizures in rats.

    PubMed

    Makeyev, Oleksandr; Liu, Xiang; Wang, Liling; Zhu, Zhenghan; Taveras, Aristides; Troiano, Derek; Medvedev, Andrei V; Besio, Walter G

    2012-01-01

    As epilepsy remains a refractory condition in about 30% of patients with complex partial seizures, electrical stimulation of the brain has recently shown potential for additive seizure control therapy. Previously, we applied noninvasive transcranial focal stimulation via novel tripolar concentric ring electrodes (TCREs) on the scalp of rats after inducing seizures with pentylenetetrazole (PTZ). We developed a close-loop system to detect seizures and automatically trigger the stimulation and evaluated its effect on the electrographic activity recorded by TCREs in rats. In our previous work the detectors of seizure onset were based on seizure-induced changes in signal power in the frequency range up to 100 Hz, while in this preliminary study we assess the feasibility of recording high frequency oscillations (HFOs) in the range up to 300 Hz noninvasively with scalp TCREs during PTZ-induced seizures. Grand average power spectral density estimate and generalized likelihood ratio tests were used to compare power of electrographic activity at different stages of seizure development in a group of rats (n= 8). The results suggest that TCREs have the ability to record HFOs from the scalp as well as that scalp-recorded HFOs can potentially be used as features for seizure onset detection.

  18. The perforant path projection to hippocampal area CA1 in the rat hippocampal-entorhinal cortex combined slice.

    PubMed

    Empson, R M; Heinemann, U

    1995-05-01

    1. The perforant path projection from layer III of the entorhinal cortex to CA1 of the hippocampus was studied within a hippocampal-entorhinal combined slice preparation. We prevented contamination from the other main hippocampal pathways by removal of CA3 and the dentate gyrus. 2. Initially the projection was mapped using field potential recordings that suggested an excitatory sink in stratum lacunosum moleculare with an associated source in stratum pyramidale. 3. However, recording intracellularly from CA1 cells, stimulation of the perforant path produced prominent fast GABAA and slow GABAB IPSPs often preceded by small EPSPs. In a small number of cells we observed EPSPs only. 4. CNQX blocked excitatory and inhibitory responses. This indicated the presence of an intervening excitatory synapse between the inhibitory interneurone and the pyramidal cell. 5. Focal bicuculline applications revealed that the major site of GABAA inhibitory input was to stratum radiatum of CA1. 6. The inhibition activated by the perforant path was very effective at reducing simultaneously activated Schaffer collateral mediated EPSPs and suprathreshold-stimulated action potentials. 7. Blockade of fast inhibition increased excitability and enhanced slow inhibition. Both increases relied upon the activation of NMDA receptors. 8. Perforant path inputs activated prominent and effective disynaptic inhibition of CA1 cells. This has significance for the output of hippocampal processing during normal behaviour and also under pathological conditions.

  19. EEG dynamical correlates of focal and diffuse causes of coma.

    PubMed

    Kafashan, MohammadMehdi; Ryu, Shoko; Hargis, Mitchell J; Laurido-Soto, Osvaldo; Roberts, Debra E; Thontakudi, Akshay; Eisenman, Lawrence; Kummer, Terrance T; Ching, ShiNung

    2017-11-15

    Rapidly determining the causes of a depressed level of consciousness (DLOC) including coma is a common clinical challenge. Quantitative analysis of the electroencephalogram (EEG) has the potential to improve DLOC assessment by providing readily deployable, temporally detailed characterization of brain activity in such patients. While used commonly for seizure detection, EEG-based assessment of DLOC etiology is less well-established. As a first step towards etiological diagnosis, we sought to distinguish focal and diffuse causes of DLOC through assessment of temporal dynamics within EEG signals. We retrospectively analyzed EEG recordings from 40 patients with DLOC with consensus focal or diffuse culprit pathology. For each recording, we performed a suite of time-series analyses, then used a statistical framework to identify which analyses (features) could be used to distinguish between focal and diffuse cases. Using cross-validation approaches, we identified several spectral and non-spectral EEG features that were significantly different between DLOC patients with focal vs. diffuse etiologies, enabling EEG-based classification with an accuracy of 76%. Our findings suggest that DLOC due to focal vs. diffuse injuries differ along several electrophysiological parameters. These results may form the basis of future classification strategies for DLOC and coma that are more etiologically-specific and therefore therapeutically-relevant.

  20. Efficacy, tolerability, and retention rates of zonisamide in older adult patients with focal-onset epilepsy: Experiences from two tertiary epilepsy centers.

    PubMed

    Doğan, Ebru Apaydın; Genç, Emine; Genç, Bülent Oğuz; Erdoğan, Çağla

    2017-11-01

    The objective of this study was to evaluate the efficacy, tolerability, and retention rates for zonisamide (ZNS) in older adult patients with focal-onset epilepsy. Chart reviews of patients aged 60years and older with focal-onset epilepsy treated with ZNS in two tertiary epilepsy centers were analyzed retrospectively. Eighty-five patients (41 males, 44 females) aged over 60years (range: 60-81) with focal-onset epilepsy treated with ZNS were identified; 55.3% of the patients (n=47) were on monotherapy. The median and average doses of ZNS doses were 200mg/day (range: 100-400) and 212.9±84.2mg/day, respectively. With ZNS treatment, 67.1% of the patients (n=57) were seizure-free for a median of 28months (range: 10-56) whereas 20% (n=17) of the patients had seizures that were unresponsive to ZNS treatment. Best seizure control was achieved in patients with poststroke epilepsy; seizure freedom was 80% in this subgroup. Overall retention rate was found to be 83.5%. There was no significant relation between receiving poly- or monotherapy and discontinuation of ZNS (p=0.18). Thirty-two of the patients (37.6%) lost weight. Median weight loss was 8kg (range: 2-16). There was no significant correlation between weight loss and the administered doses of ZNS (r=0.34; p=0.12). Despite limitations due to the retrospective design of the study, the results show that ZNS is a well-retained drug with high efficacy in older adult patients with epilepsy. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Seizure clustering.

    PubMed

    Haut, Sheryl R

    2006-02-01

    Seizure clusters, also known as repetitive or serial seizures, occur commonly in epilepsy. Clustering implies that the occurrence of one seizure may influence the probability of a subsequent seizure; thus, the investigation of the clustering phenomenon yields insights into both specific mechanisms of seizure clustering and more general concepts of seizure occurrence. Seizure clustering has been defined clinically as a number of seizures per unit time and, statistically, as a deviation from a random distribution, or interseizure interval dependence. This review explores the pathophysiology, epidemiology, and clinical implications of clustering, as well as other periodic patterns of seizure occurrence. Risk factors for experiencing clusters and potential precipitants of clustering are also addressed.

  2. A Population-Based Study of Long-term Outcomes of Cryptogenic Focal Epilepsy in Childhood: Cryptogenic Epilepsy is NOT Probably Symptomatic Epilepsy

    PubMed Central

    Wirrell, Elaine C; Grossardt, Brandon R; So, Elson L; Nickels, Katherine C

    2011-01-01

    Purpose To compare long-term outcome in a population-based group of children with cryptogenic vs symptomatic focal epilepsy diagnosed from 1980–2004 and to define the course of epilepsy in the cryptogenic group. Methods We identified all children residing in Olmsted County, MN, 1 month through 17 years with newly diagnosed, non-idiopathic focal epilepsy from 1980–2004. Children with idiopathic partial epilepsy syndromes were excluded. Medical records were reviewed to determine etiology, results of imaging and EEG studies, treatments used, and long-term outcome. Children were defined as having symptomatic epilepsy if they had a known genetic or structural/metabolic etiology, and as cryptogenic if they did not. Key Findings Of 359 children with newly-diagnosed epilepsy, 215 (60%) had non-idiopathic focal epilepsy. Of these, 206 (96%) were followed for more than 12 months. Ninety five children (46%) were classified as symptomatic. Median follow-up from diagnosis was similar in both groups, being 157 months (25%ile, 75%ile 89, 233) in the cryptogenic group vs 134 months (25%ile, 75%ile 78, 220) in the symptomatic group (p=0.26). Of 111 cryptogenic cases, 66% had normal cognition. Long-term outcome was significantly better in those with cryptogenic vs symptomatic etiology (intractable epilepsy at last follow-up, 7% vs 40%, p<0.001; seizure-freedom at last follow-up, 81% vs 55%, p<0.001). Of those who achieved seizure-freedom at final follow-up, 68% of the cryptogenic group versus only 46% of the symptomatic group were off antiepileptic medications (p=0.01). One third of the cryptogenic group had a remarkably benign disorder, with no seizures seen after initiation of medication, or in those who were untreated, after the second afebrile seizure. A further 5% had seizures within the first year but remained seizure-free thereafter. With the exception of perinatal complications, which predicted against seizure remission, no other factors were found to significantly

  3. Time-to-Seizure Modeling of Lacosamide Used in Monotherapy in Patients with Newly Diagnosed Epilepsy.

    PubMed

    Lindauer, Andreas; Laveille, Christian; Stockis, Armel

    2017-11-01

    To quantify the relationship between exposure to lacosamide monotherapy and seizure probability, and to simulate the effect of changing the dose regimen. Structural time-to-event models for dropouts (not because of a lack of efficacy) and seizures were developed using data from 883 adult patients newly diagnosed with epilepsy and experiencing focal or generalized tonic-clonic seizures, participating in a trial (SP0993; ClinicalTrials.gov identifier: NCT01243177) comparing the efficacy of lacosamide and carbamazepine controlled-release monotherapy. Lacosamide dropout and seizure models were used for simulating the effect of changing the initial target dose on seizure freedom. Repeated time-to-seizure data were described by a Weibull distribution with parameters estimated separately for the first and subsequent seizures. Daily area under the plasma concentration-time curve was related linearly to the log-hazard. Disease severity, expressed as the number of seizures during the 3 months before the trial (baseline), was a strong predictor of seizure probability: patients with 7-50 seizures at baseline had a 2.6-fold (90% confidence interval 2.01-3.31) higher risk of seizures compared with the reference two to six seizures. Simulations suggested that a 400-mg/day, rather than a 200-mg/day initial target dose for patients with seven or more seizures at baseline could potentially result in an additional 8% of seizure-free patients for 6 months at the last evaluated dose level. Patients receiving lacosamide had a slightly lower dropout risk compared with those receiving carbamazepine. Baseline disease severity was the most important predictor of seizure probability. Simulations suggest that an initial target dose >200 mg/day could potentially benefit patients with greater disease severity.

  4. Functional definition of seizure provides new insight into post-traumatic epileptogenesis.

    PubMed

    D'Ambrosio, Raimondo; Hakimian, Shahin; Stewart, Tessandra; Verley, Derek R; Fender, Jason S; Eastman, Clifford L; Sheerin, Aaron H; Gupta, Puneet; Diaz-Arrastia, Ramon; Ojemann, Jeffrey; Miller, John W

    2009-10-01

    Experimental animals' seizures are often defined arbitrarily based on duration, which may lead to misjudgement of the syndrome and failure to develop a cure. We employed a functional definition of seizures based on the clinical practice of observing epileptiform electrocorticography and simultaneous ictal behaviour, and examined post-traumatic epilepsy induced in rats by rostral parasagittal fluid percussion injury and epilepsy patients evaluated with invasive monitoring. We showed previously that rostral parasagittal fluid percussion injury induces different types of chronic recurrent spontaneous partial seizures that worsen in frequency and duration over the months post injury. However, a remarkable feature of rostral parasagittal fluid percussion injury is the occurrence, in the early months post injury, of brief (<2 s) focal, recurrent and spontaneous epileptiform electrocorticography events (EEEs) that are never observed in sham-injured animals and have electrographic appearance similar to the onset of obvious chronic recurrent spontaneous partial seizures. Simultaneous epidural-electrocorticography and scalp-electroencephalography recordings in the rat demonstrated that these short EEEs are undetectable by scalp electrocorticography. Behavioural analysis performed blinded to the electrocorticography revealed that (i) brief EEEs lasting 0.8-2 s occur simultaneously with behavioural arrest; and (ii) while behavioural arrest is part of the rat's behavioural repertoire, the probability of behavioural arrest is greatly elevated during EEEs. Moreover, spectral analysis showed that EEEs lasting 0.8-2 s occurring during periods of active behaviour with dominant theta activity are immediately followed by loss of such theta activity. We thus conclude that EEEs lasting 0.8-2 s are ictal in the rat. We demonstrate that the assessment of the time course of fluid percussion injury-induced epileptogenesis is dramatically biased by the definition of seizure employed, with

  5. Functional definition of seizure provides new insight into post-traumatic epileptogenesis

    PubMed Central

    Hakimian, Shahin; Stewart, Tessandra; Verley, Derek R.; Fender, Jason S.; Eastman, Clifford L.; Sheerin, Aaron H.; Gupta, Puneet; Diaz-Arrastia, Ramon; Ojemann, Jeffrey; Miller, John W.

    2009-01-01

    Experimental animals’ seizures are often defined arbitrarily based on duration, which may lead to misjudgement of the syndrome and failure to develop a cure. We employed a functional definition of seizures based on the clinical practice of observing epileptiform electrocorticography and simultaneous ictal behaviour, and examined post-traumatic epilepsy induced in rats by rostral parasagittal fluid percussion injury and epilepsy patients evaluated with invasive monitoring. We showed previously that rostral parasagittal fluid percussion injury induces different types of chronic recurrent spontaneous partial seizures that worsen in frequency and duration over the months post injury. However, a remarkable feature of rostral parasagittal fluid percussion injury is the occurrence, in the early months post injury, of brief (<2 s) focal, recurrent and spontaneous epileptiform electrocorticography events (EEEs) that are never observed in sham-injured animals and have electrographic appearance similar to the onset of obvious chronic recurrent spontaneous partial seizures. Simultaneous epidural-electrocorticography and scalp-electroencephalography recordings in the rat demonstrated that these short EEEs are undetectable by scalp electrocorticography. Behavioural analysis performed blinded to the electrocorticography revealed that (i) brief EEEs lasting 0.8–2 s occur simultaneously with behavioural arrest; and (ii) while behavioural arrest is part of the rat's behavioural repertoire, the probability of behavioural arrest is greatly elevated during EEEs. Moreover, spectral analysis showed that EEEs lasting 0.8–2 s occurring during periods of active behaviour with dominant theta activity are immediately followed by loss of such theta activity. We thus conclude that EEEs lasting 0.8–2 s are ictal in the rat. We demonstrate that the assessment of the time course of fluid percussion injury-induced epileptogenesis is dramatically biased by the definition of seizure employed

  6. Dissociation of spontaneous seizures and brainstem seizure thresholds in mice exposed to eight flurothyl-induced generalized seizures.

    PubMed

    Kadiyala, Sridhar B; Ferland, Russell J

    2017-03-01

    C57BL/6J mice exposed to eight flurothyl-induced generalized clonic seizures exhibit a change in seizure phenotype following a 28-day incubation period and subsequent flurothyl rechallenge. Mice now develop a complex seizure semiology originating in the forebrain and propagating into the brainstem seizure network (a forebrain→brainstem seizure). In contrast, this phenotype change does not occur in seizure-sensitive DBA/2J mice. The underlying mechanism(s) was the focus of these studies. DBA2/J mice were exposed to eight flurothyl-induced seizures (1/day) followed by 24-hour video-electroencephalographic recordings for 28-days. Forebrain and brainstem seizure thresholds were determined in C57BL/6J and DBA/2J mice following one or eight flurothyl-induced seizures, or after eight flurothyl-induced seizures, a 28-day incubation period, and final flurothyl rechallenge. Similar to C57BL/6J mice, DBA2/J mice expressed spontaneous seizures. However, unlike C57BL/6J mice, DBA2/J mice continued to have spontaneous seizures without remission. Because DBA2/J mice do not express forebrain→brainstem seizures following flurothyl rechallenge after a 28-day incubation period, this indicated that spontaneous seizures were not sufficient for the evolution of forebrain→brainstem seizures. Therefore, we determined whether brainstem seizure thresholds were changing during this repeated-flurothyl model and whether this could account for the expression of forebrain→brainstem seizures. Brainstem seizure thresholds were not different between C57BL/6J and DBA/2J mice on day one or on the last induction seizure trial (day eight). However, brainstem seizure thresholds did differ significantly on flurothyl rechallenge (day 28) with DBA/2J mice showing no lowering of their brainstem seizure thresholds. These results demonstrated that DBA/2J mice exposed to the repeated-flurothyl model develop spontaneous seizures without evidence of seizure remission and provide a new model of

  7. Seizure outcomes in non-resective epilepsy surgery: An update

    PubMed Central

    Englot, Dario J.; Birk, Harjus; Chang, Edward F.

    2016-01-01

    In approximately 30% of patients with epilepsy, seizures are refractory to medical therapy, leading to significant morbidity and increased mortality. Substantial evidence has demonstrated the benefit of surgical resection in patients with drug-resistant focal epilepsy, and in the present journal, we recently reviewed seizure outcomes in resective epilepsy surgery. However, not all patients are candidates for or amenable to open surgical resection for epilepsy. Fortunately, several non-resective surgical options are now available at various epilepsy centers, including novel therapies which have been pioneered in recent years. Ablative procedures such as stereotactic laser ablation and stereotactic radiosurgery offer minimally invasive alternatives to open surgery with relatively favorable seizure outcomes, particularly in patients with mesial temporal lobe epilepsy. For certain individuals who are not candidates for ablation or resection, palliative neuromodulation procedures such as vagus nerve stimulation, deep brain stimulation, or responsive neurostimulation may result in a significant decrease in seizure frequency and improved quality of life. Finally, disconnection procedures such as multiple subpial transections and corpus callosotomy continue to play a role in select patients with an eloquent epileptogenic zone or intractable atonic seizures, respectively. Overall, open surgical resection remains the gold standard treatment for drug-resistant epilepsy, although it is significantly under-utilized. While non-resective epilepsy procedures have not replaced the need for resection, there is hope that these additional surgical options will increase the number of patients who receive treatment for this devastating disorder - particularly individuals who are not candidates for or who have failed resection. PMID:27206422

  8. Electrographic waveform structure predicts laminar focus location in a model of temporal lobe seizures in vitro.

    PubMed

    Adams, Christopher; Adams, Natalie E; Traub, Roger D; Whittington, Miles A

    2015-01-01

    Temporal lobe epilepsy is the most common form of partial-onset epilepsy and accounts for the majority of adult epilepsy cases in most countries. A critical role for the hippocampus (and to some extent amygdala) in the pathology of these epilepsies is clear, with selective removal of these regions almost as effective as temporal lobectomy in reducing subsequent seizure risk. However, there is debate about whether hippocampus is 'victim' or 'perpetrator': The structure is ideally placed to 'broadcast' epileptiform activity to a great many other brain regions, but removal often leaves epileptiform events still occurring in cortex, particularly in adjacent areas, and recruitment of the hippocampus into seizure-like activity has been shown to be difficult in clinically-relevant models. Using a very simple model of acute epileptiform activity with known, single primary pathology (GABAA Receptor partial blockade), we track the onset and propagation of epileptiform events in hippocampus, parahippocampal areas and neocortex. In this model the hippocampus acts as a potential seizure focus for the majority of observed events. Events with hippocampal focus were far more readily propagated throughout parahippocampal areas and into neocortex than vice versa. The electrographic signature of events of hippocampal origin was significantly different to those of primary neocortical origin - a consequence of differential laminar activation. These data confirm the critical role of the hippocampus in epileptiform activity generation in the temporal lobe and suggest the morphology of non-invasive electrical recording of neocortical interictal events may be useful in confirming this role.

  9. Electrographic Waveform Structure Predicts Laminar Focus Location in a Model of Temporal Lobe Seizures In Vitro

    PubMed Central

    Adams, Christopher; Adams, Natalie E.; Traub, Roger D.; Whittington, Miles A.

    2015-01-01

    Temporal lobe epilepsy is the most common form of partial-onset epilepsy and accounts for the majority of adult epilepsy cases in most countries. A critical role for the hippocampus (and to some extent amygdala) in the pathology of these epilepsies is clear, with selective removal of these regions almost as effective as temporal lobectomy in reducing subsequent seizure risk. However, there is debate about whether hippocampus is ‘victim’ or ‘perpetrator’: The structure is ideally placed to ‘broadcast’ epileptiform activity to a great many other brain regions, but removal often leaves epileptiform events still occurring in cortex, particularly in adjacent areas, and recruitment of the hippocampus into seizure-like activity has been shown to be difficult in clinically-relevant models. Using a very simple model of acute epileptiform activity with known, single primary pathology (GABAA Receptor partial blockade), we track the onset and propagation of epileptiform events in hippocampus, parahippocampal areas and neocortex. In this model the hippocampus acts as a potential seizure focus for the majority of observed events. Events with hippocampal focus were far more readily propagated throughout parahippocampal areas and into neocortex than vice versa. The electrographic signature of events of hippocampal origin was significantly different to those of primary neocortical origin – a consequence of differential laminar activation. These data confirm the critical role of the hippocampus in epileptiform activity generation in the temporal lobe and suggest the morphology of non-invasive electrical recording of neocortical interictal events may be useful in confirming this role. PMID:25799020

  10. A comparative study of the dentate gyrus in hippocampal sclerosis in epilepsy and dementia

    PubMed Central

    Bandopadhyay, R; Liu, J Y W; Sisodiya, S M; Thom, M

    2014-01-01

    Aims: Hippocampal sclerosis (HS) is long-recognized in association with epilepsy (HSE) and more recently in the context of cognitive decline or dementia in the elderly (HSD), in some cases as a component of neurodegenerative diseases, including Alzheimer's disease (AD) and fronto-temporal lobe dementia (FTLD). There is an increased risk of seizures in AD and spontaneous epileptiform discharges in the dentate gyrus of transgenic AD models; epilepsy can be associated with an age-accelerated increase in AD-type pathology and cognitive decline. The convergence between these disease processes could be related to hippocampal pathology. HSE typically shows re-organization of both excitatory and inhibitory neuronal networks in the dentate gyrus, and is considered to be relevant to hippocampal excitability. We sought to compare the pathology of HSE and HSD, focusing on re-organization in the dentate gyrus. Methods: In nine post mortem cases with HSE and bilateral damage, 18 HSD and 11 controls we carried out immunostaining for mossy fibres (dynorphin), and interneuronal networks (NPY, calbindin and calretinin) on sections from the mid-hippocampal body. Fibre sprouting (FS) or loss of expression in the dentate gyrus was semi-quantitatively graded from grade 0 (normal) to grade 3 (marked alteration). Results: Significantly more re-organization was seen with all four markers in the HSE than HSD group (P < 0.01). Mild alterations were noted in HSD group with dynorphin (FS in 3 cases), calretinin (FS in 6 cases), NPY (FS in 11 cases) and calbindin (loss in 10 cases). In eight HSD cases, alteration was seen with more than one antibody but in no cases were the highest grades seen. We also noted NPY and, to a lesser extent, calretinin labelling of Hirano bodies in CA1 of AD cases and some older controls, but not in HSE. Conclusion: Reorganization of excitatory and inhibitory networks in the dentate gyrus is more typical of HSE. Subtle alterations in HSD may be a result of

  11. Repeat surgery for focal cortical dysplasias in children: indications and outcomes.

    PubMed

    Sacino, Matthew F; Ho, Cheng-Ying; Whitehead, Matthew T; Kao, Amy; Depositario-Cabacar, Dewi; Myseros, John S; Magge, Suresh N; Keating, Robert F; Gaillard, William D; Oluigbo, Chima O

    2017-02-01

    OBJECTIVE Focal cortical dysplasia (FCD) is a common cause of medically intractable epilepsy that often may be treated by surgery. Following resection, many patients continue to experience seizures, necessitating a decision for further surgery to achieve the desired seizure outcomes. Few studies exist on the efficacy of reoperation for intractable epilepsy due to FCD in pediatric cohorts, including the definition of prognostic factors correlated with clinical benefit from further resection. METHODS The authors retrospectively analyzed the medical records and MR images of 22 consecutive pediatric patients who underwent repeat FCD resection after unsuccessful first surgery at the Children's National Health System between March 2005 and April 2015. RESULTS Accounting for all reoperations, 13 (59%) of the 22 patients achieved complete seizure freedom and another 5 patients (23%) achieved significant improvement in seizure control. Univariate analysis demonstrated that concordance in electrocorticography (ECoG) and MRI localization (p = 0.005), and completeness of resection (p = 0.0001), were associated with seizure freedom after the first reoperation. Patients with discordant ECoG and MRI findings ultimately benefited from aggressive multilobe lobectomy or hemispherectomy. Repeat lesionectomies utilizing intraoperative MRI (iMRI; n = 9) achieved complete resection and seizure freedom in all cases. CONCLUSIONS Reoperation may be clinically beneficial in patients with intractable epilepsy due to FCD. Patients with concordant intraoperative ECoG and MRI localization may benefit from extended resection of residual dysplasia at the margins of the previous lesional cavity, and iMRI may offer benefits as a quality control mechanism to ensure that a complete resection has been accomplished. Patients with discordant findings may benefit from more aggressive resections at earlier stages to achieve better seizure control and ensure functional plasticity.

  12. Focal status epilepticus and progressive dyskinesia: A novel phenotype for glycine receptor antibody-mediated neurological disease in children.

    PubMed

    Chan, D W S; Thomas, T; Lim, M; Ling, S; Woodhall, M; Vincent, A

    2017-03-01

    Antibody-associated disorders of the central nervous system are increasingly recognised in adults and children. Some are known to be paraneoplastic, whereas in others an infective trigger is postulated. They include disorders associated with antibodies to N-methyl-d-aspartate receptor (NMDAR), voltage-gated potassium channel-complexes (VGKC-complex), GABA B receptor or glycine receptor (GlyR). With antibodies to NMDAR or VGKC-complexes, distinct clinical patterns are well characterised, but as more antibodies are discovered, the spectra of associated disorders are evolving. GlyR antibodies have been detected in patients with progressive encephalopathy with rigidity and myoclonus (PERM), or stiff man syndrome, both rare but disabling conditions. We report a case of a young child with focal seizures and progressive dyskinesia in whom GlyR antibodies were detected. Anticonvulsants and immunotherapy were effective in treating both the seizures and movement disorder with good neurological outcome and with a decline in the patient's serum GlyR-Ab titres. Glycine receptor antibodies are associated with focal status epilepticus and seizures, encephalopathy and progressive dyskinesia and should be evaluated in autoimmune encephalitis. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  13. Postoperative recovery of hippocampal contralateral diffusivity in medial temporal lobe epilepsy.

    PubMed

    Thivard, Lionel; Tanguy, Marie-Laure; Adam, Claude; Clémenceau, Stéphane; Dezamis, Edouard; Lehéricy, Stéphane; Dormont, Didier; Chiras, Jacques; Baulac, Michel; Dupont, Sophie

    2007-03-01

    To search for a recovery after surgery of mean diffusivity (MD) values in the contralateral nonsclerotic hippocampus of patients with medial temporal lobe epilepsy (MTLE) and hippocampal sclerosis (HS). Twenty-four MTLE patients (12 right-sided and 12 left-sided MTLE) and 36 healthy volunteers were investigated using diffusion tensor imaging. A region-of-interest approach was used to measure pre- and postoperative interictal hippocampal MD values in patients. Diffusion abnormalities in contralateral nonsclerotic hippocampus recovered after surgery (p<0.0001). A subgroup of 14 patients exhibited a clear increase in MD values whereas the remaining 10 patients were stable. No significant difference was found between the two subgroups for each of the electroclinical data studied including early postoperative outcome, all patients being either seizure free or with rare persistent auras. This finding suggests that diffusion abnormalities in contralateral hippocampus may represent a functional mechanism linked to the active epileptic process.

  14. Prevention of plasticity of endocannabinoid signaling inhibits persistent limbic hyperexcitability caused by developmental seizures.

    PubMed

    Chen, Kang; Neu, Axel; Howard, Allyson L; Földy, Csaba; Echegoyen, Julio; Hilgenberg, Lutz; Smith, Martin; Mackie, Ken; Soltesz, Ivan

    2007-01-03

    Depolarization-induced suppression of inhibition (DSI) is an endocannabinoid-mediated short-term plasticity mechanism that couples postsynaptic Ca2+ rises to decreased presynaptic GABA release. Whether the gain of this retrograde synaptic mechanism is subject to long-term modulation by glutamatergic excitatory inputs is not known. Here, we demonstrate that activity-dependent long-term DSI potentiation takes place in hippocampal slices after tetanic stimulation of Schaffer collateral synapses. This activity-dependent, long-term plasticity of endocannabinoid signaling was specific to GABAergic synapses, as it occurred without increases in the depolarization-induced suppression of excitation. Induction of tetanus-induced DSI potentiation in vitro required a complex pathway involving AMPA/kainate and metabotropic glutamate receptor as well as CB1 receptor activation. Because DSI potentiation has been suggested to play a role in persistent limbic hyperexcitability after prolonged seizures in the developing brain, we used these mechanistic insights into activity-dependent DSI potentiation to test whether interference with the induction of DSI potentiation prevents seizure-induced long-term hyperexcitability. The results showed that the in vitro, tetanus-induced DSI potentiation was occluded by previous in vivo fever-induced (febrile) seizures, indicating a common pathway. Accordingly, application of CB1 receptor antagonists during febrile seizures in vivo blocked the seizure-induced persistent DSI potentiation, abolished the seizure-induced upregulation of CB1 receptors, and prevented the emergence of long-term limbic hyperexcitability. These results reveal a new form of activity-dependent, long-term plasticity of endocannabinoid signaling at perisomatic GABAergic synapses, and demonstrate that blocking the induction of this plasticity abolishes the long-term effects of prolonged febrile seizures in the developing brain.

  15. Oral Uncaria rhynchophylla (UR) reduces kainic acid-induced epileptic seizures and neuronal death accompanied by attenuating glial cell proliferation and S100B proteins in rats.

    PubMed

    Lin, Yi-Wen; Hsieh, Ching-Liang

    2011-05-17

    Epilepsy is a common clinical syndrome with recurrent neuronal discharges in cerebral cortex and hippocampus. Here we aim to determine the protective role of Uncaria rhynchophylla (UR), an herbal drug belong to Traditional Chinese Medicine (TCM), on epileptic rats. To address this issue, we tested the effect of UR on kainic acid (KA)-induced epileptic seizures and further investigate the underlying mechanisms. Oral UR successfully decreased neuronal death and discharges in hippocampal CA1 pyramidal neurons. The population spikes (PSs) were decreased from 4.1 ± 0.4 mV to 2.1 ± 0.3 mV in KA-induced epileptic seizures and UR-treated groups, respectively. Oral UR protected animals from neuronal death induced by KA treatment (from 34 ± 4.6 to 191.7 ± 48.6 neurons/field) through attenuating glial cell proliferation and S100B protein expression but not GABAA and TRPV1 receptors. The above results provide detail mechanisms underlying the neuroprotective action of UR on KA-induced epileptic seizure in hippocampal CA1 neurons. Crown Copyright © 2011. Published by Elsevier Ireland Ltd. All rights reserved.

  16. Seizures

    MedlinePlus

    ... Your Child Has a Seizure Print en español Crisis convulsivas (convulsiones) Seizures are caused by a sudden surge of electrical activity in the brain. A seizure usually affects how a person looks or acts for a ...

  17. Slow Spatial Recruitment of Neocortex during Secondarily Generalized Seizures and Its Relation to Surgical Outcome

    PubMed Central

    Martinet, Louis-Emmanuel; Ahmed, Omar J.; Lepage, Kyle Q.; Cash, Sydney S.

    2015-01-01

    Understanding the spatiotemporal dynamics of brain activity is crucial for inferring the underlying synaptic and nonsynaptic mechanisms of brain dysfunction. Focal seizures with secondary generalization are traditionally considered to begin in a limited spatial region and spread to connected areas, which can include both pathological and normal brain tissue. The mechanisms underlying this spread are important to our understanding of seizures and to improve therapies for surgical intervention. Here we study the properties of seizure recruitment—how electrical brain activity transitions to large voltage fluctuations characteristic of spike-and-wave seizures. We do so using invasive subdural electrode arrays from a population of 16 patients with pharmacoresistant epilepsy. We find an average delay of ∼30 s for a broad area of cortex (8 × 8 cm) to be recruited into the seizure, at an estimated speed of ∼4 mm/s. The spatiotemporal characteristics of recruitment reveal two categories of patients: one in which seizure recruitment of neighboring cortical regions follows a spatially organized pattern consistent from seizure to seizure, and a second group without consistent spatial organization of activity during recruitment. The consistent, organized recruitment correlates with a more regular, compared with small-world, connectivity pattern in simulation and successful surgical treatment of epilepsy. We propose that an improved understanding of how the seizure recruits brain regions into large amplitude voltage fluctuations provides novel information to improve surgical treatment of epilepsy and highlights the slow spread of massive local activity across a vast extent of cortex during seizure. PMID:26109670

  18. Canonical Transient Receptor Channel 5 (TRPC5) and TRPC1/4 Contribute to Seizure and Excitotoxicity by Distinct Cellular Mechanisms

    PubMed Central

    Phelan, Kevin D.; Shwe, U Thaung; Abramowitz, Joel; Wu, Hong; Rhee, Sung W.; Howell, Matthew D.; Gottschall, Paul E.; Freichel, Marc; Flockerzi, Veit; Birnbaumer, Lutz

    2013-01-01

    Seizures are the manifestation of highly synchronized burst firing of a large population of cortical neurons. Epileptiform bursts with an underlying plateau potential in neurons are a cellular correlate of seizures. Emerging evidence suggests that the plateau potential is mediated by neuronal canonical transient receptor potential (TRPC) channels composed of members of the TRPC1/4/5 subgroup. We previously showed that TRPC1/4 double-knockout (DKO) mice lack epileptiform bursting in lateral septal neurons and exhibit reduced seizure-induced neuronal cell death, but surprisingly have unaltered pilocarpine-induced seizures. Here, we report that TRPC5 knockout (KO) mice exhibit both significantly reduced seizures and minimal seizure-induced neuronal cell death in the hippocampus. Interestingly, epileptiform bursting induced by agonists for metabotropic glutamate receptors in the hippocampal CA1 area is unaltered in TRPC5 KO mice, but is abolished in TRPC1 KO and TRPC1/4 DKO mice. In contrast, long-term potentiation is greatly reduced in TRPC5 KO mice, but is normal in TRPC1 KO and TRPC1/4 DKO mice. The distinct changes from these knockouts suggest that TRPC5 and TRPC1/4 contribute to seizure and excitotoxicity by distinct cellular mechanisms. Furthermore, the reduced seizure and excitotoxicity and normal spatial learning exhibited in TRPC5 KO mice suggest that TRPC5 is a promising novel molecular target for new therapy. PMID:23188715

  19. Canonical transient receptor channel 5 (TRPC5) and TRPC1/4 contribute to seizure and excitotoxicity by distinct cellular mechanisms.

    PubMed

    Phelan, Kevin D; Shwe, U Thaung; Abramowitz, Joel; Wu, Hong; Rhee, Sung W; Howell, Matthew D; Gottschall, Paul E; Freichel, Marc; Flockerzi, Veit; Birnbaumer, Lutz; Zheng, Fang

    2013-02-01

    Seizures are the manifestation of highly synchronized burst firing of a large population of cortical neurons. Epileptiform bursts with an underlying plateau potential in neurons are a cellular correlate of seizures. Emerging evidence suggests that the plateau potential is mediated by neuronal canonical transient receptor potential (TRPC) channels composed of members of the TRPC1/4/5 subgroup. We previously showed that TRPC1/4 double-knockout (DKO) mice lack epileptiform bursting in lateral septal neurons and exhibit reduced seizure-induced neuronal cell death, but surprisingly have unaltered pilocarpine-induced seizures. Here, we report that TRPC5 knockout (KO) mice exhibit both significantly reduced seizures and minimal seizure-induced neuronal cell death in the hippocampus. Interestingly, epileptiform bursting induced by agonists for metabotropic glutamate receptors in the hippocampal CA1 area is unaltered in TRPC5 KO mice, but is abolished in TRPC1 KO and TRPC1/4 DKO mice. In contrast, long-term potentiation is greatly reduced in TRPC5 KO mice, but is normal in TRPC1 KO and TRPC1/4 DKO mice. The distinct changes from these knockouts suggest that TRPC5 and TRPC1/4 contribute to seizure and excitotoxicity by distinct cellular mechanisms. Furthermore, the reduced seizure and excitotoxicity and normal spatial learning exhibited in TRPC5 KO mice suggest that TRPC5 is a promising novel molecular target for new therapy.

  20. Absence seizure

    MedlinePlus

    Seizure - petit mal; Seizure - absence; Petit mal seizure; Epilepsy - absence seizure ... Abou-Khalil BW, Gallagher MJ, Macdonald RL. Epilepsies. In: Daroff ... Practice . 7th ed. Philadelphia, PA: Elsevier; 2016:chap 101. ...

  1. Phase shift in the 24-hour rhythm of hippocampal EEG spiking activity in a rat model of temporal lobe epilepsy

    PubMed Central

    Stanley, David A.; Talathi, Sachin S.; Parekh, Mansi B.; Cordiner, Daniel J.; Zhou, Junli; Mareci, Thomas H.; Ditto, William L.

    2013-01-01

    For over a century epileptic seizures have been known to cluster at specific times of the day. Recent studies have suggested that the circadian regulatory system may become permanently altered in epilepsy, but little is known about how this affects neural activity and the daily pattern of seizures. To investigate, we tracked long-term changes in the rate of spontaneous hippocampal EEG spikes (SPKs) in a rat model of temporal lobe epilepsy. In healthy animals, SPKs oscillated with near 24-h period; however, after injury by status epilepticus, a persistent phase shift of ∼12 h emerged in animals that later went on to develop chronic spontaneous seizures. Additional measurements showed that global 24-h rhythms, including core body temperature and theta state transitions, did not phase shift. Instead, we hypothesized that locally impaired circadian input to the hippocampus might be responsible for the SPK phase shift. This was investigated with a biophysical computer model in which we showed that subtle changes in the relative strengths of circadian input could produce a phase shift in hippocampal neural activity. MRI provided evidence that the medial septum, a putative circadian relay center for the hippocampus, exhibits signs of damage and therefore could contribute to local circadian impairment. Our results suggest that balanced circadian input is critical to maintaining natural circadian phase in the hippocampus and that damage to circadian relay centers, such as the medial septum, may disrupt this balance. We conclude by discussing how abnormal circadian regulation may contribute to the daily rhythms of epileptic seizures and related cognitive dysfunction. PMID:23678009

  2. The effects of high-frequency oscillations in hippocampal electrical activities on the classification of epileptiform events using artificial neural networks

    NASA Astrophysics Data System (ADS)

    Chiu, Alan W. L.; Jahromi, Shokrollah S.; Khosravani, Houman; Carlen, Peter L.; Bardakjian, Berj L.

    2006-03-01

    The existence of hippocampal high-frequency electrical activities (greater than 100 Hz) during the progression of seizure episodes in both human and animal experimental models of epilepsy has been well documented (Bragin A, Engel J, Wilson C L, Fried I and Buzsáki G 1999 Hippocampus 9 137-42 Khosravani H, Pinnegar C R, Mitchell J R, Bardakjian B L, Federico P and Carlen P L 2005 Epilepsia 46 1-10). However, this information has not been studied between successive seizure episodes or utilized in the application of seizure classification. In this study, we examine the dynamical changes of an in vitro low Mg2+ rat hippocampal slice model of epilepsy at different frequency bands using wavelet transforms and artificial neural networks. By dividing the time-frequency spectrum of each seizure-like event (SLE) into frequency bins, we can analyze their burst-to-burst variations within individual SLEs as well as between successive SLE episodes. Wavelet energy and wavelet entropy are estimated for intracellular and extracellular electrical recordings using sufficiently high sampling rates (10 kHz). We demonstrate that the activities of high-frequency oscillations in the 100-400 Hz range increase as the slice approaches SLE onsets and in later episodes of SLEs. Utilizing the time-dependent relationship between different frequency bands, we can achieve frequency-dependent state classification. We demonstrate that activities in the frequency range 100-400 Hz are critical for the accurate classification of the different states of electrographic seizure-like episodes (containing interictal, preictal and ictal states) in brain slices undergoing recurrent spontaneous SLEs. While preictal activities can be classified with an average accuracy of 77.4 ± 6.7% utilizing the frequency spectrum in the range 0-400 Hz, we can also achieve a similar level of accuracy by using a nonlinear relationship between 100-400 Hz and <4 Hz frequency bands only.

  3. Focal cortical malformations in children with early infantile epilepsy and PCDH19 mutations: case report.

    PubMed

    Kurian, Mary; Korff, Christian M; Ranza, Emmanuelle; Bernasconi, Andrea; Lübbig, Anja; Nangia, Srishti; Ramelli, Gian Paolo; Wohlrab, Gabriele; Nordli, Douglas R; Bast, Thomas

    2018-01-01

    In this case report we assess the occurrence of cortical malformations in children with early infantile epilepsy associated with variants of the gene protocadherin 19 (PCDH19). We describe the clinical course, and electrographic, imaging, genetic, and neuropathological features in a cohort of female children with pharmacoresistant epilepsy. All five children (mean age 10y) had an early onset of epilepsy during infancy and a predominance of fever sensitive seizures occurring in clusters. Cognitive impairment was noted in four out of five patients. Radiological evidence of cortical malformations was present in all cases and, in two patients, validated by histology. Sanger sequencing and Multiplex Ligation-dependent Probe Amplification analysis of PCDH19 revealed pathogenic variants in four patients. In one patient, array comparative genomic hybridization showed a microdeletion encompassing PCDH19. We propose molecular testing and analysis of PCDH19 in patients with pharmacoresistant epilepsy, with onset in early infancy, seizures in clusters, and fever sensitivity. Structural lesions are to be searched in patients with PCDH19 pathogenic variants. Further, PCDH19 analysis should be considered in epilepsy surgery evaluation even in the presence of cerebral structural lesions. Focal cortical malformations and monogenic epilepsy syndromes may coexist. Structural lesions are to be searched for in patients with protocadherin 19 (PCDH19) pathogenic variants with refractory focal seizures. © 2017 Mac Keith Press.

  4. A study of 43 patients with panayiotopoulos syndrome, a common and benign childhood seizure susceptibility.

    PubMed

    Lada, Christina; Skiadas, Konstantinos; Theodorou, Virginia; Loli, Nomiki; Covanis, Athanasios

    2003-01-01

    To determine prevalence, clinical, EEG features, and prognosis of Panayiotopoulos syndrome and to examine the proposition that clinical manifestations are more important than EEG findings. We analyzed retrospectively the clinical and EEG records of 1,340 children with one or more focal seizures seen in the last 18 years, supplemented with a prospective study from 1998. Panayiotopoulos syndrome was defined by clinical criteria, mainly ictal emesis, irrespective of EEG findings. We analyzed 43 of 90 patients with Panayiotopoulos syndrome who were seizure free >2 years. Girls predominated. Mean age at first seizure was 5 years. Seizures consisted mainly of autonomic manifestations; ictal emesis was often the first symptom, culminating in vomiting in 86%. Of nonautonomic manifestations, lateral eye deviation was the most common; visual symptoms were exceptional. Impairment of consciousness ensued in all seizures, half of which ended with hemi or generalized convulsions. Nearly 46.5% of cases had at least one seizure >30 min, constituting autonomic status epilepticus. Seizures during sleep (84%) were more common than those in wakefulness. EEG showed occipital spikes in 29 patients. Of the other 14 cases, five had extraoccipital abnormalities or brief generalized discharges, and nine had normal awake and sleep EEG. Prognosis was excellent. All 43 children have been free of seizures for > or =2 years, 53% having a single seizure, and 47%, an average two to three seizures. Panayiotopoulos syndrome is common and needs wider recognition. EEG shows occipital or extraoccipital abnormalities, is normal in one third of patients, and does not determine clinical manifestations or prognosis, which is excellent despite the high prevalence of lengthy seizures.

  5. The effects of different fractions of Coriandrum sativum on pentylenetetrazole-induced seizures and brain tissues oxidative damage in rats.

    PubMed

    Anaeigoudari, Akbar; Hosseini, Mahmoud; Karami, Reza; Vafaee, Farzaneh; Mohammadpour, Toktam; Ghorbani, Ahmad; Sadeghnia, Hamid Reza

    2016-01-01

    In the present work, the effects of different fractions of Coriandrum sativum (C. sativum), on pentylenetetrazole (PTZ)-induced seizures and brain tissues oxidative damage were investigated in rats. The rats were divided into the following groups: (1) vehicle, (2) PTZ (90 mg/kg), (3) water fraction (WF) of C. sativum (25 and 100 mg/kg), (4) n-butanol fraction (NBF) of C. sativum (25 and 100 mg/kg), and (5) ethyl acetate fraction (EAF) of C. sativum (25 and 100 mg/kg). The first generalized tonic-clonic seizures (GTCS) latency in groups treated with 100 mg /kg of WF or EAF was significantly higher than that of PTZ group (p<0.01). In contrast to WF, the EAF and NBF were not effective in increasing the first minimal clonic seizure (MCS) latency. Malondialdehyde (MDA) levels in both cortical and hippocampal tissues of PTZ group were significantly higher than those of control animals (p<0.001). Pretreatment with WF, NBF, or EAF resulted in a significant reduction in the MDA levels of hippocampi (p<0.01 - p<0.001). Following PTZ administration, a significant reduction in total thiol groups was observed in the brain tissues (p<0.05). Pretreatment with WF and NBF significantly elevated thiol concentrations in cortical and hippocampal tissues, respectively (p<0.05). The present study showed that different fractions of C. sativum possess antioxidant activity in the brain and WF and EAF of this plant have anticonvulsant effects.

  6. Pre-seizure architecture of the local connections of the epileptic focus examined via graph-theory.

    PubMed

    Vecchio, Fabrizio; Miraglia, Francesca; Vollono, Catello; Fuggetta, Filomena; Bramanti, Placido; Cioni, Beatrice; Rossini, Paolo Maria

    2016-10-01

    Epilepsy is characterized by unpredictable and sudden paroxysmal neuronal firing occurrences and sometimes evolving in clinically evident seizure. To predict seizure event, small-world characteristic in nine minutes before seizure, divided in three 3-min periods (T0, T1, T2) were investigated. Intracerebral recordings were obtained from 10 patients with drug resistant focal epilepsy examined by means of stereotactically implanted electrodes; analysis was focused in a period of low spiking (Baseline) and during two seizures. Networks' architecture is undirected and weighted. Electrodes' contacts close to epileptic focus are the vertices, edges are weighted by mscohere (=magnitude squared coherence). Differences were observed between Baseline and T1 and between Baseline and T2 in theta band; and between Baseline and T1, Baseline and T2, and near-significant difference between T0 and T2 in Alpha 2 band. Moreover, an intra-band index was computed for small worldness as difference between Theta and Alpha 2. It was found a growing index trend from Baseline to T2. Cortical network features a specific pre-seizure architecture which could predict the incoming epileptic seizure. Through this study future researches could investigate brain connectivity modifications approximating a clinical seizure also in order to address a preventive therapy. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  7. Seizures and Teens: Stress, Sleep, & Seizures

    ERIC Educational Resources Information Center

    Shafer, Patricia Osborne

    2007-01-01

    Most parents are used to erratic sleep patterns and mood swings in their teenagers. When these occur in an adolescent with seizures, however, the parent may wonder if sleep and mood problems are related to seizures. Sorting out the cause and effects of sleep in an adolescent with seizures can be confusing. Since stress can be a contributor to both…

  8. The promise of subtraction ictal SPECT co-registered to MRI for improved seizure localization in pediatric epilepsies: Affecting factors and relationship to the surgical outcome

    PubMed Central

    Stamoulis, Catherine; Verma, Nishant; Kaulas, Himanshu; Halford, Jonathan J.; Duffy, Frank H.; Pearl, Phillip L.; Treves, S. Ted

    2016-01-01

    Objective Ictal SPECT is promising for accurate non-invasive localization of the epileptogenic brain tissue in focal epilepsies. However, high quality ictal scans require meticulous attention to the seizure onset. In a relatively large cohort of pediatric patients, this study investigated the impact of the timing of radiotracer injection, MRI findings and seizure characteristics on ictal SPECT localizations, and the relationship between concordance of ictal SPECT, scalp EEG and resected area with seizure freedom following epilepsy surgery. Methods Scalp EEG and ictal SPECT studies from 95 patients (48 males and 47 females, median age = 11 years, (25th, 75th) quartiles = (6.0, 14.75) years) with pharmacoresistant focal epilepsy and no prior epilepsy surgery were reviewed. The ictal SPECT result was examined as a function of the radiotracer injection delay, seizure duration, epilepsy etiology, cerebral lobe of seizure onset identified by EEG and MRI findings. Thirty two patients who later underwent epilepsy surgery had postoperative seizure freedom data at <1, 6 and 12 months. Results Sixty patients (63.2%) had positive SPECT localizations - 51 with a hyperperfused region that was concordant with the cerebral lobe of seizure origin identified by EEG and 9 with discordant localizations. Of these, 35 patients (58.3%) had temporal and 25 (41.7%) had extratemporal seizures. The ictal SPECT result was significantly correlated with the injection delay (p<0.01) and cerebral lobe of seizure onset (specifically frontal versus temporal; p = 0.02) but not MRI findings (p = 0.33), epilepsy etiology (p ≥ 0.27) or seizure duration (p = 0.20). Concordance of SPECT, scalp EEG and resected area was significantly correlated with seizure freedom at 6 months after surgery (p=0.04). Significance Ictal SPECT holds promise as a powerful source imaging tool for presurgical planning in pediatric epilepsies. To optimize the SPECT result the radiotracer injection delay should be minimized to

  9. The promise of subtraction ictal SPECT co-registered to MRI for improved seizure localization in pediatric epilepsies: Affecting factors and relationship to the surgical outcome.

    PubMed

    Stamoulis, Catherine; Verma, Nishant; Kaulas, Himanshu; Halford, Jonathan J; Duffy, Frank H; Pearl, Phillip L; Treves, S Ted

    2017-01-01

    Ictal SPECT is promising for accurate non-invasive localization of the epileptogenic brain tissue in focal epilepsies. However, high quality ictal scans require meticulous attention to the seizure onset. In a relatively large cohort of pediatric patients, this study investigated the impact of the timing of radiotracer injection, MRI findings and seizure characteristics on ictal SPECT localizations, and the relationship between concordance of ictal SPECT, scalp EEG and resected area with seizure freedom following epilepsy surgery. Scalp EEG and ictal SPECT studies from 95 patients (48 males and 47 females, median age=11years, (25th, 75th) quartiles=(6.0, 14.75) years) with pharmacoresistant focal epilepsy and no prior epilepsy surgery were reviewed. The ictal SPECT result was examined as a function of the radiotracer injection delay, seizure duration, epilepsy etiology, cerebral lobe of seizure onset identified by EEG and MRI findings. Thirty two patients who later underwent epilepsy surgery had postoperative seizure freedom data at <1, 6 and 12 months. Sixty patients (63.2%) had positive SPECT localizations - 51 with a hyperperfused region that was concordant with the cerebral lobe of seizure origin identified by EEG and 9 with discordant localizations. Of these, 35 patients (58.3%) had temporal and 25 (41.7%) had extratemporal seizures. The ictal SPECT result was significantly correlated with the injection delay (p<0.01) and cerebral lobe of seizure onset (specifically frontal versus temporal; p=0.02) but not MRI findings (p=0.33), epilepsy etiology (p≥0.27) or seizure duration (p=0.20). Concordance of SPECT, scalp EEG and resected area was significantly correlated with seizure freedom at 6 months after surgery (p=0.04). Ictal SPECT holds promise as a powerful source imaging tool for presurgical planning in pediatric epilepsies. To optimize the SPECT result the radiotracer injection delay should be minimized to≤25s, although the origin of seizure onset

  10. Cannabidiol attenuates seizures and social deficits in a mouse model of Dravet syndrome

    PubMed Central

    Kaplan, Joshua S.; Stella, Nephi; Catterall, William A.; Westenbroek, Ruth E.

    2017-01-01

    Worldwide medicinal use of cannabis is rapidly escalating, despite limited evidence of its efficacy from preclinical and clinical studies. Here we show that cannabidiol (CBD) effectively reduced seizures and autistic-like social deficits in a well-validated mouse genetic model of Dravet syndrome (DS), a severe childhood epilepsy disorder caused by loss-of-function mutations in the brain voltage-gated sodium channel NaV1.1. The duration and severity of thermally induced seizures and the frequency of spontaneous seizures were substantially decreased. Treatment with lower doses of CBD also improved autistic-like social interaction deficits in DS mice. Phenotypic rescue was associated with restoration of the excitability of inhibitory interneurons in the hippocampal dentate gyrus, an important area for seizure propagation. Reduced excitability of dentate granule neurons in response to strong depolarizing stimuli was also observed. The beneficial effects of CBD on inhibitory neurotransmission were mimicked and occluded by an antagonist of GPR55, suggesting that therapeutic effects of CBD are mediated through this lipid-activated G protein-coupled receptor. Our results provide critical preclinical evidence supporting treatment of epilepsy and autistic-like behaviors linked to DS with CBD. We also introduce antagonism of GPR55 as a potential therapeutic approach by illustrating its beneficial effects in DS mice. Our study provides essential preclinical evidence needed to build a sound scientific basis for increased medicinal use of CBD. PMID:28973916

  11. Thalamic stimulation to improve level of consciousness after seizures: evaluation of electrophysiology and behavior.

    PubMed

    Gummadavelli, Abhijeet; Motelow, Joshua E; Smith, Nicholas; Zhan, Qiong; Schiff, Nicholas D; Blumenfeld, Hal

    2015-01-01

    Understanding the neural mechanisms that support human consciousness is an important frontier in neuroscience and medicine. We previously developed a rodent model of temporal lobe seizures that recapitulates the human electroencephalography (EEG) signature of ictal and postictal neocortical slow waves associated with behavioral impairments in level of consciousness. The mechanism of slow-wave production in epilepsy may involve suppression of the subcortical arousal systems including the brainstem and intralaminar thalamic nuclei. We hypothesized that intralaminar thalamic stimulation may lead to electrophysiologic and functional rescue from postictal slow waves and behavioral arrest. We electrically stimulated the central lateral thalamic nucleus (a member of the intralaminar nuclei) under anesthesia and after electrically induced hippocampal seizures in anesthetized and in awake-behaving animal model preparations. We demonstrated a proof-of-principle restoration of electrophysiologic and behavioral measures of consciousness by stimulating the intralaminar thalamic nuclei after seizures. We measured decreased cortical slow waves and increased desynchronization and multiunit activity in the cortex with thalamic stimulation following seizures. Functionally, thalamic stimulation produced resumption of exploratory behaviors in the postictal state. Targeting of nodes in the neural circuitry of consciousness has important medical implications. Impaired consciousness with epilepsy has dangerous consequences including decreased school/work performance, social stigmatization, and impaired airway protection. These data suggest a novel therapeutic approach for restoring consciousness after seizures. If paired with responsive neurostimulation, this may allow rapid implementation to improve level of consciousness in patients with epilepsy. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

  12. Peroxisome proliferator-activated receptors γ/mitochondrial uncoupling protein 2 signaling protects against seizure-induced neuronal cell death in the hippocampus following experimental status epilepticus

    PubMed Central

    2012-01-01

    Background Status epilepticus induces subcellular changes that may lead to neuronal cell death in the hippocampus. However, the mechanism of seizure-induced neuronal cell death remains unclear. The mitochondrial uncoupling protein 2 (UCP2) is expressed in selected regions of the brain and is emerged as an endogenous neuroprotective molecule in many neurological disorders. We evaluated the neuroprotective role of UCP2 against seizure-induced hippocampal neuronal cell death under experimental status epilepticus. Methods In Sprague–Dawley rats, kainic acid (KA) was microinjected unilaterally into the hippocampal CA3 subfield to induce prolonged bilateral seizure activity. Oxidized protein level, translocation of Bcl-2, Bax and cytochrome c between cytosol and mitochondria, and expression of peroxisome proliferator-activated receptors γ (PPARγ) and UCP2 were examined in the hippocampal CA3 subfield following KA-induced status epilepticus. The effects of microinjection bilaterally into CA3 area of a PPARγ agonist, rosiglitazone or a PPARγ antagonist, GW9662 on UCP2 expression, induced superoxide anion (O2· -) production, oxidized protein level, mitochondrial respiratory chain enzyme activities, translocation of Bcl-2, Bax and cytochrome c, and DNA fragmentation in bilateral CA3 subfields were examined. Results Increased oxidized proteins and mitochondrial or cytosol translocation of Bax or cytochrome c in the hippocampal CA3 subfield was observed 3–48 h after experimental status epilepticus. Expression of PPARγ and UCP2 increased 12–48 h after KA-induced status epilepticus. Pretreatment with rosiglitazone increased UCP2 expression, reduced protein oxidation, O2· - overproduction and dysfunction of mitochondrial Complex I, hindered the translocation of Bax and cytochrome c, and reduced DNA fragmentation in the CA3 subfield. Pretreatment with GW9662 produced opposite effects. Conclusions Activation of PPARγ upregulated mitochondrial UCP2 expression

  13. Hypoglycemia and risk of seizures: a retrospective cross-sectional study.

    PubMed

    Imad, Halawa; Johan, Zelano; Eva, Kumlien

    2015-02-01

    Few studies have been dedicated to assess neurological symptoms in relations to hypoglycemia. In this study we investigated the association between different levels of hypoglycemia and the occurrence of epileptic seizures in patients without a prior diagnosis of epilepsy. A retrospective cross-sectional study. We identified 388 individuals from a laboratory database in Swedish regional hospital who had been found to have a glucose value of ≤3.5 mM between January and December 2009. Medical records were reviewed. Hypoglycemia was defined at three different categories: 0-2 mM (40 patients), 2.1-3 mM (154 patients) and 3.1-3.5 mM (194 patients). 14 patients had disturbance of consciousness including 3 with seizures. The majority of cases had coma, a generalized tonic-clonic seizure was seen only when s-glucose dropped below 2.0 mM. Two cases with focal seizure were noted, one at s-glucose 2.0 mM, and one at s-glucose 3.3 mM. The absolute risks (95% confidence interval) for having major neurological symptoms at glucose levels of ≤2.0 mM were 0.25 (0.13-0.41), 0.02 (0-0.06) at 2.1-3.0 mM and 0.01 (0-0.03) at 3.1-3.5 mM. Coma is the most common neurological symptom related to hypoglycemia. Epileptic seizures are rare and not as common as previously assumed. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  14. Treatment with lacosamide impedes generalized seizures in a rodent model of cortical dysplasia.

    PubMed

    Nemes, Ashley D; O'Dwyer, Rebecca; Najm, Imad M; Ying, Zhong; Gonzalez-Martinez, Jorge; Alexopoulos, Andreas V

    2017-10-01

    Epilepsy is a common neurologic disorder resulting in spontaneous, recurrent seizures. About 30-40% of patients are not responsive to pharmacologic therapies. This may be due to the differences between individual patients such as etiology, underlying pathophysiology, and seizure focus, and it highlights the importance of new drug discovery and testing in this field. Our goal was to determine the efficacy of lacosamide (LCM), a drug approved for the treatment of focal seizures, in a model of generalized epilepsy with cortical dysplasia (CD). We sought to compare LCM to levetiracetam (LEV), a drug that is currently used for the treatment of both partial and generalized epilepsy and to test its proficiency. Pregnant rats were irradiated to produce pups with malformed cortices in a model of CD, which will be referred to as the "first hit." Adult animals, developed normally (NL) and irradiated (XRT), were surgically implanted with electroencephalography (EEG) electrodes. Baseline EEG was recorded on all rats prior to pretreatments with either LCM, LEV, or placebo (PBO). After 30 min, all rats were injected with a subconvulsive dose of pentylenetetrazole (PTZ), a γ-aminobutyric acid receptor A (GABA A ) antagonist used to provoke generalized seizures as a "second hit." LCM and LEV were both effective against seizures induced by PTZ. XRT rats had a higher seizure incidence with longer and more severe seizures than NL rats. Seizure duration was decreased with both LCM and LEV in all animals. In XRT rats, there was a significant reduction in acute seizure incidence and severity with both LCM and LEV after PTZ injection. Our results suggest that LCM could be used as a potential treatment option for generalized epilepsy with CD as the underlying pathology. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  15. 22q11.2 deletion syndrome lowers seizure threshold in adult patients without epilepsy.

    PubMed

    Wither, Robert G; Borlot, Felippe; MacDonald, Alex; Butcher, Nancy J; Chow, Eva W C; Bassett, Anne S; Andrade, Danielle M

    2017-06-01

    Previous studies examining seizures in patients with 22q11.2 deletion syndrome (22q11.2DS) have focused primarily on children and adolescents. In this study we investigated the prevalence and characteristics of seizures and epilepsy in an adult 22q11.2DS population. The medical records of 202 adult patients with 22q11.2DS were retrospectively reviewed for documentation of seizures, electroencephalography (EEG) reports, and magnetic resonance imaging (MRI) findings. Epilepsy status was assigned in accordance with 2010 International League Against Epilepsy Classification. Of 202 patients, 32 (15.8%) had a documented history of seizure. Of these 32, 23 (71.8%) had acute symptomatic seizures, usually associated with hypocalcemia and/or antipsychotic or antidepressant use. Nine patients (9/32, 28%; 9/202, 4%) met diagnostic criteria for epilepsy. Two patients had genetic generalized epilepsy; two patients had focal seizures of unknown etiology; two had epilepsy due to malformations of cortical development; in two the epilepsy was due to acquired structural changes; and in one patient the epilepsy could not be further classified. Similarly to children, the prevalence of epilepsy and acute symptomatic seizures in adults with 22q11.2DS is higher than in the general population. Hypocalcemia continues to be a risk factor for adults, but differently from kids, the main cause of seizures in adults with 22q11.2DS is exposure to antipsychotics and antidepressants. Further prospective studies are warranted to investigate how 22q11.2 microdeletion leads to an overall decreased seizure threshold. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  16. Apoptosis of mouse hippocampal cells induced by Taenia crassiceps metacestode factor.

    PubMed

    Zepeda, N; Solano, S; Copitin, N; Chávez, J L; Fernández, A M; García, F; Tato, P; Molinari, J L

    2017-03-01

    Seizures, headache, depression and neurological deficits are the signs and symptoms most frequently reported in human neurocysticercosis. However, the cause of the associated learning and memory deficits is unknown. Here, we used Taenia crassiceps infection in mice as a model of human cysticercosis. The effects of T. crassiceps metacestode infection or T. crassiceps metacestode factor (MF) treatment on mouse hippocampal cells were studied; control mice were included. At 45 days after infection or treatment of the mice with MF, all mice were anaesthetized and perfused transcardially with saline followed by phosphate-buffered 10% formalin. Then the brains were carefully removed. Coronal sections stained using several techniques were analysed. Extensive and significant apoptosis was found in the experimental animals, mainly in the dentate gyrus, CA1, CA2, CA3 and neighbouring regions, in comparison with the apparently intact cells from control mice (P < 0.01). These results suggest that neurological deficits, especially the learning and memory deficits, may be generated by extensive apoptosis of hippocampal cells.

  17. Dual Pathology in Rasmussen's Encephalitis: A Report of Coexistent Focal Cortical Dysplasia and Review of the Literature.

    PubMed

    Prayson, Richard A

    2012-01-01

    Rasmussen's encephalitis is a well-established, albeit rare cause of medically intractable epilepsy. In a small number of Rasmussen's cases, a second pathology is identified, which independently can cause medically intractable seizures (dual pathology). This paper documents a case of a 13-year-old male who presented with medically intractable epilepsy. The patient underwent a series of surgical resections, early on resulting in a diagnosis of focal cortical dysplasia and later yielding a diagnosis of coexistent Rasmussen's encephalitis, marked by chronic inflammation, microglial nodules, and focal cortical atrophy, combined with focal cortical dysplasia (Palmini et al. type IIA, ILAE type IIA). The literature on dual pathology in the setting of Rasmussen's encephalitis is reviewed.

  18. Dual Pathology in Rasmussen's Encephalitis: A Report of Coexistent Focal Cortical Dysplasia and Review of the Literature

    PubMed Central

    Prayson, Richard A.

    2012-01-01

    Rasmussen's encephalitis is a well-established, albeit rare cause of medically intractable epilepsy. In a small number of Rasmussen's cases, a second pathology is identified, which independently can cause medically intractable seizures (dual pathology). This paper documents a case of a 13-year-old male who presented with medically intractable epilepsy. The patient underwent a series of surgical resections, early on resulting in a diagnosis of focal cortical dysplasia and later yielding a diagnosis of coexistent Rasmussen's encephalitis, marked by chronic inflammation, microglial nodules, and focal cortical atrophy, combined with focal cortical dysplasia (Palmini et al. type IIA, ILAE type IIA). The literature on dual pathology in the setting of Rasmussen's encephalitis is reviewed. PMID:23056977

  19. Identifying seizure clusters in patients with psychogenic nonepileptic seizures.

    PubMed

    Baird, Grayson L; Harlow, Lisa L; Machan, Jason T; Thomas, Dave; LaFrance, W C

    2017-08-01

    The present study explored how seizure clusters may be defined for those with psychogenic nonepileptic seizures (PNES), a topic for which there is a paucity of literature. The sample was drawn from a multisite randomized clinical trial for PNES; seizure data are from participants' seizure diaries. Three possible cluster definitions were examined: 1) common clinical definition, where ≥3 seizures in a day is considered a cluster, along with two novel statistical definitions, where ≥3 seizures in a day are considered a cluster if the observed number of seizures statistically exceeds what would be expected relative to a patient's: 1) average seizure rate prior to the trial, 2) observed seizure rate for the previous seven days. Prevalence of clusters was 62-68% depending on cluster definition used, and occurrence rate of clusters was 6-19% depending on cluster definition. Based on these data, clusters seem to be common in patients with PNES, and more research is needed to identify if clusters are related to triggers and outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Increase in α-tubulin modifications in the neuronal processes of hippocampal neurons in both kainic acid-induced epileptic seizure and Alzheimer's disease.

    PubMed

    Vu, Hang Thi; Akatsu, Hiroyasu; Hashizume, Yoshio; Setou, Mitsutoshi; Ikegami, Koji

    2017-01-09

    Neurodegeneration includes acute changes and slow-developing alterations, both of which partly involve common cellular machinery. During neurodegeneration, neuronal processes are impaired along with dysregulated post-translational modifications (PTMs) of cytoskeletal proteins. In neuronal processes, tubulin undergoes unique PTMs including a branched form of modification called glutamylation and loss of the C-terminal tyrosine residue and the penultimate glutamic acid residue forming Δ2-tubulin. Here, we investigated the state of two PTMs, glutamylation and Δ2 form, in both acute and slow-developing neurodegenerations, using a newly generated monoclonal antibody, DTE41, which had 2-fold higher affinity to glutamylated Δ2-tubulin, than to unmodified Δ2-tubulin. DTE41 recognised glutamylated Δ2-tubulin preferentially in immunostaining than in enzyme-linked immunosorbent assay and immunoblotting. In normal mouse brain, DTE41 stained molecular layer of the cerebellum as well as synapse-rich regions in pyramidal neurons of the cerebral cortex. In kainic acid-induced epileptic seizure, DTE41-labelled signals were increased in the hippocampal CA3 region, especially in the stratum lucidum. In the hippocampi of post-mortem patients with Alzheimer's disease, intensities of DTE41 staining were increased in mossy fibres in the CA3 region as well as in apical dendrites of the pyramidal neurons. Our findings indicate that glutamylation on Δ2-tubulin is increased in both acute and slow-developing neurodegeneration.

  1. Ginkgo biloba L. attenuates spontaneous recurrent seizures and associated neurological conditions in lithium-pilocarpine rat model of temporal lobe epilepsy through inhibition of mammalian target of rapamycin pathway hyperactivation.

    PubMed

    Mazumder, Arindam Ghosh; Sharma, Pallavi; Patial, Vikram; Singh, Damanpreet

    2017-05-23

    Ginkgo biloba L. (Ginkgoaceae) has been widely used in traditional medicine for variety of neurological conditions particularly behavioral and memory impairments. The present study was envisaged to explore the effect of a standardized fraction of Ginkgo biloba leaves (GBbf) in rat model of lithium-pilocarpine induced spontaneous recurrent seizures, and associated behavioral impairments and cognitive deficit. Rats showing appearance of spontaneous recurrent seizures following lithium pilocarpine (LiPc)-induced status epilepticus (SE) were treated with different doses of GBbf or vehicle for subsequent 4 weeks. The severity of seizures and aggression in rats were scored following treatment with GBbf. Further, open field, forced swim, novel object recognition and Morris water maze tests were conducted. Histopathological, protein levels and gene expression studies were performed in the isolated brains. Treatment with GBbf reduced seizure severity score and aggression in epileptic animals. Improved spatial cognitive functions and recognition memory, along with reduction in anxiety-like behavior were also observed in the treated animals. Histopathological examination by Nissl staining showed reduction in neuronal damage in the hippocampal pyramidal layer. The dentate gyrus and Cornu Ammonis 3 regions of the hippocampus showed reduction in mossy fiber sprouting. GBbf treatment attenuated ribosomal S6 and pS6 proteins, and hippocampal mTOR, Rps6 and Rps6kb1 mRNA levels. The results of present study concluded that GBbf treatment suppressed lithium-pilocarpine induced spontaneous recurrent seizures severity and incidence with improved cognitive functions, reduced anxiety-like behavior and aggression. The effect was found to be due to inhibition of mTOR pathway hyperactivation linked with recurrent seizures. Copyright © 2017. Published by Elsevier B.V.

  2. Lithium-methomyl induced seizures in rats: A new model of status epilepticus?

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kaminski, Rafal M.; Blaszczak, Piotr; Dekundy, Andrzej

    2007-03-15

    Behavioral, electroencephalographic (EEG) and neuropathological effects of methomyl, a carbamate insecticide reversibly inhibiting acetylcholinesterase activity, were studied in naive or lithium chloride (24 h, 3 mEq/kg, s.c.) pretreated male Wistar rats. In naive animals, methomyl with equal potency produced motor limbic seizures and fatal status epilepticus. Thus, the CD50 values (50% convulsant dose) for these seizure endpoints were almost equal to the LD50 (50% lethal dose) of methomyl (13 mg/kg). Lithium pretreated rats were much more susceptible to convulsant, but not lethal effect of methomyl. CD50 values of methomyl for motor limbic seizures and status epilepticus were reduced by lithiummore » pretreatment to 3.7 mg/kg (a 3.5-fold decrease) and 5.2 mg/kg (a 2.5-fold decrease), respectively. In contrast, lithium pretreatment resulted in only 1.3-fold decrease of LD50 value of methomyl (9.9 mg/kg). Moreover, lithium-methomyl treated animals developed a long-lasting status epilepticus, which was not associated with imminent lethality observed in methomyl-only treated rats. Scopolamine (10 mg/kg) or diazepam (10 mg/kg) protected all lithium-methomyl treated rats from convulsions and lethality. Cortical and hippocampal EEG recordings revealed typical epileptic discharges that were consistent with behavioral seizures observed in lithium-methomyl treated rats. In addition, convulsions induced by lithium-methomyl treatment were associated with widespread neurodegeneration of limbic structures. Our observations indicate that lithium pretreatment results in separation between convulsant and lethal effects of methomyl in rats. As such, seizures induced by lithium-methomyl administration may be an alternative to lithium-pilocarpine model of status epilepticus, which is associated with high lethality.« less

  3. Model-guided control of hippocampal discharges by local direct current stimulation.

    PubMed

    Mina, Faten; Modolo, Julien; Recher, Fanny; Dieuset, Gabriel; Biraben, Arnaud; Benquet, Pascal; Wendling, Fabrice

    2017-05-10

    Neurostimulation is an emerging treatment for drug-resistant epilepsies when surgery is contraindicated. Recent clinical results demonstrate significant seizure frequency reduction in epileptic patients, however the mechanisms underlying this therapeutic effect are largely unknown. This study aimed at gaining insights into local direct current stimulation (LDCS) effects on hyperexcitable tissue, by i) analyzing the impact of electrical currents locally applied on epileptogenic brain regions, and ii) characterizing currents achieving an "anti-epileptic" effect (excitability reduction). First, a neural mass model of hippocampal circuits was extended to accurately reproduce the features of hippocampal paroxysmal discharges (HPD) observed in a mouse model of epilepsy. Second, model predictions regarding current intensity and stimulation polarity were confronted to in vivo mice recordings during LDCS (n = 8). The neural mass model was able to generate realistic hippocampal discharges. Simulation of LDCS in the model pointed at a significant decrease of simulated HPD (in duration and occurrence rate, not in amplitude) for cathodal stimulation, which was successfully verified experimentally in epileptic mice. Despite the simplicity of our stimulation protocol, these results contribute to a better understanding of clinical benefits observed in epileptic patients with implanted neurostimulators. Our results also provide further support for model-guided design of neuromodulation therapy.

  4. Temporal Lobe Epilepsy: Quantitative MR Volumetry in Detection of Hippocampal Atrophy

    PubMed Central

    Farid, Nikdokht; Girard, Holly M.; Kemmotsu, Nobuko; Smith, Michael E.; Magda, Sebastian W.; Lim, Wei Y.; Lee, Roland R.

    2012-01-01

    Purpose: To determine the ability of fully automated volumetric magnetic resonance (MR) imaging to depict hippocampal atrophy (HA) and to help correctly lateralize the seizure focus in patients with temporal lobe epilepsy (TLE). Materials and Methods: This study was conducted with institutional review board approval and in compliance with HIPAA regulations. Volumetric MR imaging data were analyzed for 34 patients with TLE and 116 control subjects. Structural volumes were calculated by using U.S. Food and Drug Administration–cleared software for automated quantitative MR imaging analysis (NeuroQuant). Results of quantitative MR imaging were compared with visual detection of atrophy, and, when available, with histologic specimens. Receiver operating characteristic analyses were performed to determine the optimal sensitivity and specificity of quantitative MR imaging for detecting HA and asymmetry. A linear classifier with cross validation was used to estimate the ability of quantitative MR imaging to help lateralize the seizure focus. Results: Quantitative MR imaging–derived hippocampal asymmetries discriminated patients with TLE from control subjects with high sensitivity (86.7%–89.5%) and specificity (92.2%–94.1%). When a linear classifier was used to discriminate left versus right TLE, hippocampal asymmetry achieved 94% classification accuracy. Volumetric asymmetries of other subcortical structures did not improve classification. Compared with invasive video electroencephalographic recordings, lateralization accuracy was 88% with quantitative MR imaging and 85% with visual inspection of volumetric MR imaging studies but only 76% with visual inspection of clinical MR imaging studies. Conclusion: Quantitative MR imaging can depict the presence and laterality of HA in TLE with accuracy rates that may exceed those achieved with visual inspection of clinical MR imaging studies. Thus, quantitative MR imaging may enhance standard visual analysis, providing a

  5. Autopsy-confirmed hippocampal-sparing Alzheimer's disease with delusional jealousy as initial manifestation.

    PubMed

    Fujishiro, Hiroshige; Iritani, Shuji; Hattori, Miho; Sekiguchi, Hirotaka; Matsunaga, Shinji; Habuchi, Chikako; Torii, Youta; Umeda, Kentaro; Ozaki, Norio; Yoshida, Mari; Fujita, Kiyoshi

    2015-09-01

    Alzheimer's disease (AD) is clinically characterized by gradual onset over years with worsening of cognition. The initial and most prominent cognitive deficit is commonly memory dysfunction. However, a subset of AD cases has less hippocampal atrophy than would be expected relative to the predominance of cortical atrophy. These hippocampal-sparing cases have distinctive clinical features, including the presence of focal cortical clinical syndromes. Given that previous studies have indicated that severe hippocampal atrophy corresponds to prominent loss of episodic memory, it is likely that memory impairment is initially absent in hippocampal-sparing AD cases. Here, we report on a patient with an 8-year history of delusional jealousy with insidious onset who was clinically diagnosed as possible AD and pathologically confirmed to have AD with relatively preserved neurons in the hippocampus. This patient had delusional jealousy with a long pre-dementia stage, which initially was characterized by lack of memory impairment. Head magnetic resonance imaging findings showed preserved hippocampal volume with bilateral enlarged ventricles and mild-to-moderate cortical atrophy. Head single-photon emission computed tomography revealed severely decreased regional cerebral blood flow in the right temporal lobe. The resolution of the delusion was attributed to pharmacotherapy by an acetylcholinesterase inhibitor, suggesting that the occurrence of delusional jealousy was due to the disease process of AD. Although the neural basis of delusional jealousy remains unclear, this hippocampal-sparing AD case may be classified as an atypical presentation of AD. © 2015 The Authors. Psychogeriatrics © 2015 Japanese Psychogeriatric Society.

  6. Drug-resistant focal epilepsy in women of childbearing age: Reproduction and the effect of epilepsy surgery.

    PubMed

    Fabris, Rachel R; Cascino, Teresa Griffin; Mandrekar, Jay; Marsh, W Richard; Meyer, Frederic B; Cascino, Gregory D

    2016-07-01

    surgery (p=0.0036 and 0.0060, respectively). Patients who received fewer antiepileptic drug medication trials by the time of surgery also had a greater change in the number of births after surgery (p=0.0362). Seizure onset localization and lateralization, presurgical seizure frequency, age at seizure onset, duration of epilepsy, and postoperative seizure outcome were not statistically significant factors. The present retrospective observational study provides additional evidence for the importance of early surgical treatment in women with drug-resistant focal epilepsy. Patients who had received fewer medications prior to surgery were more likely to experience an increase in births following surgery. The significance of these findings requires further investigation but may support a role for earlier surgical intervention in the management of drug-resistant focal epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Exploring the capability of wireless near infrared spectroscopy as a portable seizure detection device for epilepsy patients.

    PubMed

    Jeppesen, Jesper; Beniczky, Sándor; Johansen, Peter; Sidenius, Per; Fuglsang-Frederiksen, Anders

    2015-03-01

    Near infrared spectroscopy (NIRS) has proved useful in measuring significant hemodynamic changes in the brain during epileptic seizures. The advance of NIRS-technology into wireless and portable devices raises the possibility of using the NIRS-technology for portable seizure detection. This study used NIRS to measure changes in oxygenated (HbO), deoxygenated (HbR), and total hemoglobin (HbT) at left and right side of the frontal lobe in 33 patients with epilepsy undergoing long-term video-EEG monitoring. Fifteen patients had 34 focal seizures (20 temporal-, 11 frontal-, 2 parietal-lobe, one unspecific) recorded and analyzed with NIRS. Twelve parameters consisting of maximum increase and decrease changes of HbO, HbR and HbT during seizures (1 min before- to 3 min after seizure-onset) for left and right side, were compared with the patients' own non-seizure periods (a 2-h period and a 30-min exercise-period). In both non-seizure periods 4 min moving windows with maximum overlapping were applied to find non-seizure maxima of the 12 parameters. Detection was defined as positive when seizure maximum change exceeded non-seizure maximum change. When analyzing the 12 parameters separately the positive seizure detection was in the range of 6-24%. The increase in hemodynamics was in general better at detecting seizures (15-24%) than the decrease in hemodynamics (6-18%) (P=0.02). NIRS did not seem to be a suitable technology for generic seizure detection given the device, settings, and methods used in this study. There are still several challenges to overcome before the NIRS-technology can be used as a home-monitoring seizure detection device. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  8. Serotonin depletion increases seizure susceptibility and worsens neuropathological outcomes in kainate model of epilepsy.

    PubMed

    Maia, Gisela H; Brazete, Cátia S; Soares, Joana I; Luz, Liliana L; Lukoyanov, Nikolai V

    2017-09-01

    Serotonin is implicated in the regulation of seizures, but whether or not it can potentiate the effects of epileptogenic factors is not fully established. Using the kainic acid model of epilepsy in rats, we tested the effects of serotonin depletion on (1) susceptibility to acute seizures, (2) development of spontaneous recurrent seizures and (3) behavioral and neuroanatomical sequelae of kainic acid treatment. Serotonin was depleted by pretreating rats with p-chlorophenylalanine. In different groups, kainic acid was injected at 3 different doses: 6.5mg/kg, 9.0mg/kg or 12.5mg/kg. A single dose of 6.5mg/kg of kainic acid reliably induced status epilepticus in p-chlorophenylalanine-pretreated rats, but not in saline-pretreated rats. The neuroexcitatory effects of kainic acid in the p-chlorophenylalanine-pretreated rats, but not in saline-pretreated rats, were associated with the presence of tonic-clonic convulsions and high lethality. Compared to controls, a greater portion of serotonin-depleted rats showed spontaneous recurrent seizures after kainic acid injections. Loss of hippocampal neurons and spatial memory deficits associated with kainic acid treatment were exacerbated by prior depletion of serotonin. The present findings are of particular importance because they suggest that low serotonin activity may represent one of the major risk factors for epilepsy and, thus, offer potentially relevant targets for prevention of epileptogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Under what conditions is recognition spared relative to recall after selective hippocampal damage in humans?

    PubMed

    Holdstock, J S; Mayes, A R; Roberts, N; Cezayirli, E; Isaac, C L; O'Reilly, R C; Norman, K A

    2002-01-01

    The claim that recognition memory is spared relative to recall after focal hippocampal damage has been disputed in the literature. We examined this claim by investigating object and object-location recall and recognition memory in a patient, YR, who has adult-onset selective hippocampal damage. Our aim was to identify the conditions under which recognition was spared relative to recall in this patient. She showed unimpaired forced-choice object recognition but clearly impaired recall, even when her control subjects found the object recognition task to be numerically harder than the object recall task. However, on two other recognition tests, YR's performance was not relatively spared. First, she was clearly impaired at an equivalently difficult yes/no object recognition task, but only when targets and foils were very similar. Second, YR was clearly impaired at forced-choice recognition of object-location associations. This impairment was also unrelated to difficulty because this task was no more difficult than the forced-choice object recognition task for control subjects. The clear impairment of yes/no, but not of forced-choice, object recognition after focal hippocampal damage, when targets and foils are very similar, is predicted by the neural network-based Complementary Learning Systems model of recognition. This model postulates that recognition is mediated by hippocampally dependent recollection and cortically dependent familiarity; thus hippocampal damage should not impair item familiarity. The model postulates that familiarity is ineffective when very similar targets and foils are shown one at a time and subjects have to identify which items are old (yes/no recognition). In contrast, familiarity is effective in discriminating which of similar targets and foils, seen together, is old (forced-choice recognition). Independent evidence from the remember/know procedure also indicates that YR's familiarity is normal. The Complementary Learning Systems model can

  10. Event-Associated Oxygen Consumption Rate Increases ca. Five-Fold When Interictal Activity Transforms into Seizure-Like Events In Vitro.

    PubMed

    Schoknecht, Karl; Berndt, Nikolaus; Rösner, Jörg; Heinemann, Uwe; Dreier, Jens P; Kovács, Richard; Friedman, Alon; Liotta, Agustin

    2017-09-07

    Neuronal injury due to seizures may result from a mismatch of energy demand and adenosine triphosphate (ATP) synthesis. However, ATP demand and oxygen consumption rates have not been accurately determined, yet, for different patterns of epileptic activity, such as interictal and ictal events. We studied interictal-like and seizure-like epileptiform activity induced by the GABA A antagonist bicuculline alone, and with co-application of the M-current blocker XE-991, in rat hippocampal slices. Metabolic changes were investigated based on recording partial oxygen pressure, extracellular potassium concentration, and intracellular flavine adenine dinucleotide (FAD) redox potential. Recorded data were used to calculate oxygen consumption and relative ATP consumption rates, cellular ATP depletion, and changes in FAD/FADH₂ ratio by applying a reactive-diffusion and a two compartment metabolic model. Oxygen-consumption rates were ca. five times higher during seizure activity than interictal activity. Additionally, ATP consumption was higher during seizure activity (~94% above control) than interictal activity (~15% above control). Modeling of FAD transients based on partial pressure of oxygen recordings confirmed increased energy demand during both seizure and interictal activity and predicted actual FAD autofluorescence recordings, thereby validating the model. Quantifying metabolic alterations during epileptiform activity has translational relevance as it may help to understand the contribution of energy supply and demand mismatches to seizure-induced injury.

  11. Long term outcome of temporal lobe epilepsy surgery: analyses of 140 consecutive patients

    PubMed Central

    Jutila, L; Immonen, A; Mervaala, E; Partanen, J; Partanen, K; Puranen, M; Kalviainen, R; Alafuzoff, I; Hurskainen, H; Vapalahti, M; Ylinen, A

    2002-01-01

    Objective: To analyse the long term results of temporal lobe epilepsy surgery in a national epilepsy surgery centre for adults, and to evaluate preoperative factors predicting a good postoperative outcome on long term follow up. Methods: Longitudinal follow up of 140 consecutive adult patients operated on for drug resistant temporal lobe epilepsy. Results: 46% of patients with unilateral temporal lobe epilepsy became seizure-free, 10% had only postoperative auras, and 15% had rare seizures on follow up for (mean (SD)) 5.4 (2.6) years, range 0.25 to 10.5 years. The best outcome was after introduction of a standardised magnetic resonance (MR) imaging protocol (1993–99): in unilateral temporal lobe epilepsy, 52% of patients became seizure-free, 7% had only postoperative auras, and 17% had rare seizures (median follow up 3.8 years, range 0.25 to 6.5 years); in palliative cases (incomplete removal of focus), a reduction in seizures of at least 80% was achieved in 71% of cases (median follow up 3.1 years, range 1.1 to 6.8 years). Most seizure relapses (86%) occurred within one year of the operation, and outcome at one year did not differ from the long term outcome. Unilateral hippocampal atrophy with or without temporal cortical atrophy on qualitative MR imaging (p < 0.001, odds ratio (OR) 5.2, 95% confidence interval (CI) 2.0 to 13.7), other unitemporal structural lesions on qualitative MR imaging (p ≤ 0.001, OR 6.9, 95% CI 2.2 to 21.5), onset of epilepsy before the age of five years (p < 0.05, OR 2.9, 95% CI 1.2 to 7.2), and focal seizures with ictal impairment of consciousness and focal ictal EEG as a predominant seizure type (p < 0.05, OR 3.4, 95% CI 1.2 to 9.1) predicted Engel I–II outcome. Hippocampal volume reduction of at least 1 SD from the mean of controls on the side of the seizure onset (p < 0.05, OR 3.1, 95% CI 1.1 to 9.2) also predicted Engel I–II outcome. Conclusions: Outcome at one year postoperatively is highly predictive of long term outcome

  12. Nicotine increases eclampsia-like seizure threshold and attenuates microglial activity in rat hippocampus through the α7 nicotinic acetylcholine receptor.

    PubMed

    Li, Xiaolan; Han, Xinjia; Bao, Junjie; Liu, Yuanyuan; Ye, Aihua; Thakur, Mukesh; Liu, Huishu

    2016-07-01

    A considerable number of studies have demonstrated that nicotine, a α7-nicotinic acetylcholine receptor (α7-nAChR) agonist, can dampen immune response through the cholinergic anti-inflammatory pathway. Evidence suggests that inflammation plays a critical role in eclampsia, which contributes to maternal and fetal morbidity and mortality. In the present study, possible anti-inflammation and neuro-protective effects of nicotine via α7-nAChRs have been investigated after inducing eclampsia-like seizures in rats. Rat eclampsia-like models were established by administering lipopolysaccharide (LPS) plus pentylenetetrazol (PTZ) in pregnant rats. Rats were given nicotine from gestation day (GD) 14-19. Then, clinical symptoms were detected. Seizure severity was recorded by behavioral tests, serum levels of inflammatory cytokines were measured by Luminex assays, microglia and astrocyte expressions were detected by immunofluorescence, and changes in neuronal number in the hippocampal CA1 region among different groups were detected by Nissl staining. Our results revealed that nicotine effectively improved fetal outcomes. Furthermore, it significantly decreased systolic blood pressure, and maternal serum levels of Th1 cytokines (TNF-α, IL-1β, IL-6 and IL-12P70) and an IL-17 cytokine (IL-17A), and dramatically increased eclampsia-like seizure threshold. Moreover, this attenuated neuronal loss and decreased the expression of microglial activation markers of the hippocampal CA1 region in the eclampsia-like group. Additionally, pretreatment with α-bungarotoxin, a selective α7-nAChR antagonist could prevent the protective effects of nicotine in eclampsia-like model rats. Our findings indicate that the administration of nicotine may attenuate microglial activity and increase eclampsia-like seizure threshold in rat hippocampus through the α7 nicotinic receptor. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. A comparative study of the dentate gyrus in hippocampal sclerosis in epilepsy and dementia.

    PubMed

    Bandopadhyay, R; Liu, J Y W; Sisodiya, S M; Thom, M

    2014-02-01

    Hippocampal sclerosis (HS) is long-recognized in association with epilepsy (HSE ) and more recently in the context of cognitive decline or dementia in the elderly (HSD ), in some cases as a component of neurodegenerative diseases, including Alzheimer's disease (AD) and fronto-temporal lobe dementia (FTLD). There is an increased risk of seizures in AD and spontaneous epileptiform discharges in the dentate gyrus of transgenic AD models; epilepsy can be associated with an age-accelerated increase in AD-type pathology and cognitive decline. The convergence between these disease processes could be related to hippocampal pathology. HSE typically shows re-organization of both excitatory and inhibitory neuronal networks in the dentate gyrus, and is considered to be relevant to hippocampal excitability. We sought to compare the pathology of HSE and HSD , focusing on re-organization in the dentate gyrus. In nine post mortem cases with HSE and bilateral damage, 18 HSD and 11 controls we carried out immunostaining for mossy fibres (dynorphin), and interneuronal networks (NPY, calbindin and calretinin) on sections from the mid-hippocampal body. Fibre sprouting (FS) or loss of expression in the dentate gyrus was semi-quantitatively graded from grade 0 (normal) to grade 3 (marked alteration). Significantly more re-organization was seen with all four markers in the HSE than HSD group (P < 0.01). Mild alterations were noted in HSD group with dynorphin (FS in 3 cases), calretinin (FS in 6 cases), NPY (FS in 11 cases) and calbindin (loss in 10 cases). In eight HSD cases, alteration was seen with more than one antibody but in no cases were the highest grades seen. We also noted NPY and, to a lesser extent, calretinin labelling of Hirano bodies in CA1 of AD cases and some older controls, but not in HSE . Reorganization of excitatory and inhibitory networks in the dentate gyrus is more typical of HSE . Subtle alterations in HSD may be a result of increased hippocampal excitability

  14. Absence Seizure (Petit Mal Seizure)

    MedlinePlus

    ... people have many episodes daily, which interfere with school or daily activities. A child may have absence seizures for some time before an adult notices the seizures, because they're so brief. A decline in a child's learning ability may be the first sign of this ...

  15. Correlation between magnetoencephalography-based "clusterectomy" and postoperative seizure freedom.

    PubMed

    Vadera, Sumeet; Jehi, Lara; Burgess, Richard C; Shea, Katherine; Alexopoulos, Andreas V; Mosher, John; Gonzalez-Martinez, Jorge; Bingaman, William

    2013-06-01

    During the presurgical evaluation of patients with medically intractable focal epilepsy, a variety of noninvasive studies are performed to localize the hypothetical epileptogenic zone and guide the resection. Magnetoencephalography (MEG) is becoming increasingly used in the clinical realm for this purpose. No investigators have previously reported on coregisteration of MEG clusters with postoperative resection cavities to evaluate whether complete "clusterectomy" (resection of the area associated with MEG clusters) was performed or to compare these findings with postoperative seizure-free outcomes. The authors retrospectively reviewed the charts and imaging studies of 65 patients undergoing MEG followed by resective epilepsy surgery from 2009 until 2012 at the Cleveland Clinic. Preoperative MEG studies were fused with postoperative MRI studies to evaluate whether clusters were within the resected area. These data were then correlated with postoperative seizure freedom. Sixty-five patients were included in this study. The average duration of follow-up was 13.9 months, the mean age at surgery was 23.1 years, and the mean duration of epilepsy was 13.7 years. In 30 patients, the main cluster was located completely within the resection cavity, in 28 it was completely outside the resection cavity, and in 7 it was partially within the resection cavity. Seventy-four percent of patients were seizure free at 12 months after surgery, and this rate decreased to 60% at 24 months. Improved likelihood of seizure freedom was seen with complete clusterectomy in patients with localization outside the temporal lobe (extra-temporal lobe epilepsy) (p = 0.04). In patients with preoperative MEG studies that show clusters in surgically accessible areas outside the temporal lobe, we suggest aggressive resection to improve the chances for seizure freedom. When the cluster is found within the temporal lobe, further diagnostic testing may be required to better localize the epileptogenic zone.

  16. Posterior cortex epilepsy surgery in childhood and adolescence: Predictors of long-term seizure outcome.

    PubMed

    Ramantani, Georgia; Stathi, Angeliki; Brandt, Armin; Strobl, Karl; Schubert-Bast, Susanne; Wiegand, Gert; Korinthenberg, Rudolf; van Velthoven, Vera; Zentner, Josef; Schulze-Bonhage, Andreas; Bast, Thomas

    2017-03-01

    We aimed to investigate the long-term seizure outcome of children and adolescents who were undergoing epilepsy surgery in the parietooccipital cortex and determine their predictive factors. We retrospectively analyzed the data of 50 consecutive patients aged 11.1 (mean) ± 5.1 (standard deviation) years at surgery. All patients but one had a magnetic resonance imaging (MRI)-visible lesion. Resections were parietal in 40%, occipital in 32%, and parietooccipital in 28% cases; 24% patients additionally underwent a resection of the posterior border of the temporal lobe. Etiology included focal cortical dysplasia in 44%, benign tumors (dysembryoplastic neuroepithelial tumor, ganglioglioma, angiocentric glioma, and pilocystic astrocytoma) in 32%, peri- or postnatal ischemic lesions in 16%, and tuberous sclerosis in 8% cases. At last follow-up (mean 8 years, range 1.5-18 years), 60% patients remained seizure-free (Engel class I): 30% had discontinued and 20% had reduced antiepileptic drugs. Most seizure recurrences (71%) occurred within the first 6 months, and only three patients presented with seizures ≥2 years after surgery. Independent predictors of seizure recurrence included left-sided as well as parietal epileptogenic zones and resections. Longer epilepsy duration to surgery was identified as the only modifiable independent predictor of seizure recurrence. Our study demonstrates that posterior cortex epilepsy surgery is highly effective in terms of lasting seizure control and antiepileptic drug cessation in selected pediatric candidates. Most importantly, our data supports the early consideration of surgical intervention in children and adolescents with refractory posterior cortex epilepsy. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  17. Seizure-induced alterations in fast-spiking basket cell GABA currents modulate frequency and coherence of gamma oscillation in network simulations

    NASA Astrophysics Data System (ADS)

    Proddutur, Archana; Yu, Jiandong; Elgammal, Fatima S.; Santhakumar, Vijayalakshmi

    2013-12-01

    (-54 mV). When FS-BCs were activated by biologically based dendritic synaptic inputs, enhancing gGABA-extra reduced the frequency and coherence of FS-BC firing when EGABA was shunting and increased average FS-BC firing when EGABA was depolarizing. Shifting EGABA from shunting to depolarizing potentials consistently increased network frequency to and above high gamma frequencies (>80 Hz). Since gamma oscillations may contribute to learning and memory processing [Fell et al., Nat. Neurosci. 4, 1259 (2001); Jutras et al., J. Neurosci. 29, 12521 (2009); Wang, Physiol. Rev. 90, 1195 (2010)], our demonstration that network oscillations are modulated by extrasynaptic inhibition in FS-BCs suggests that neuroactive compounds that act on extrasynaptic GABA receptors could impact memory formation by modulating hippocampal gamma oscillations. The simulation results indicate that the depolarized FS-BC GABA reversal, observed after experimental seizures, together with enhanced spillover extrasynaptic GABA currents are likely to promote generation of focal high frequency activity associated with epileptic networks.

  18. The effects of different fractions of Coriandrum sativum on pentylenetetrazole-induced seizures and brain tissues oxidative damage in rats

    PubMed Central

    Anaeigoudari, Akbar; Hosseini, Mahmoud; Karami, Reza; Vafaee, Farzaneh; Mohammadpour, Toktam; Ghorbani, Ahmad; Sadeghnia, Hamid Reza

    2016-01-01

    Objective: In the present work, the effects of different fractions of Coriandrum sativum (C. sativum), on pentylenetetrazole (PTZ)-induced seizures and brain tissues oxidative damage were investigated in rats. Materials and Methods: The rats were divided into the following groups: (1) vehicle, (2) PTZ (90 mg/kg), (3) water fraction (WF) of C. sativum (25 and 100 mg/kg), (4) n-butanol fraction (NBF) of C. sativum (25 and 100 mg/kg), and (5) ethyl acetate fraction (EAF) of C. sativum (25 and 100 mg/kg). Results: The first generalized tonic-clonic seizures (GTCS) latency in groups treated with 100 mg /kg of WF or EAF was significantly higher than that of PTZ group (p<0.01). In contrast to WF, the EAF and NBF were not effective in increasing the first minimal clonic seizure (MCS) latency. Malondialdehyde (MDA) levels in both cortical and hippocampal tissues of PTZ group were significantly higher than those of control animals (p<0.001). Pretreatment with WF, NBF, or EAF resulted in a significant reduction in the MDA levels of hippocampi (p<0.01 - p<0.001). Following PTZ administration, a significant reduction in total thiol groups was observed in the brain tissues (p<0.05). Pretreatment with WF and NBF significantly elevated thiol concentrations in cortical and hippocampal tissues, respectively (p<0.05). Conclusion: The present study showed that different fractions of C. sativum possess antioxidant activity in the brain and WF and EAF of this plant have anticonvulsant effects. PMID:27222836

  19. Use of BIS VISTA bilateral monitor for diagnosis of intraoperative seizures, a case report.

    PubMed

    Iturri Clavero, F; Tamayo Medel, G; de Orte Sancho, K; González Uriarte, A; Iglesias Martínez, A; Martínez Ruíz, A

    2015-12-01

    Changes in BIS (bispectral index) VISTA bilateral monitoring system associated with intraoperative episodes of generalized and focal seizures, during total intravenous anesthesia for resection of a left frontal parasagittal meningioma, are herein described. Copyright © 2014 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. AMPA GluA1-flip targeted oligonucleotide therapy reduces neonatal seizures and hyperexcitability

    PubMed Central

    Lykens, Nicole M.; Reddi, Jyoti M.

    2017-01-01

    Glutamate-activated α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPA-Rs) mediate the majority of excitatory neurotransmission in brain and thus are major drug targets for diseases associated with hyperexcitability or neurotoxicity. Due to the critical nature of AMPA-Rs in normal brain function, typical AMPA-R antagonists have deleterious effects on cognition and motor function, highlighting the need for more precise modulators. A dramatic increase in the flip isoform of alternatively spliced AMPA-R GluA1 subunits occurs post-seizure in humans and animal models. GluA1-flip produces higher gain AMPA channels than GluA1-flop, increasing network excitability and seizure susceptibility. Splice modulating oligonucleotides (SMOs) bind to pre-mRNA to influence alternative splicing, a strategy that can be exploited to develop more selective drugs across therapeutic areas. We developed a novel SMO, GR1, which potently and specifically decreased GluA1-flip expression throughout the brain of neonatal mice lasting at least 60 days after single intracerebroventricular injection. GR1 treatment reduced AMPA-R mediated excitatory postsynaptic currents at hippocampal CA1 synapses, without affecting long-term potentiation or long-term depression, cellular models of memory, or impairing GluA1-dependent cognition or motor function in mice. Importantly, GR1 demonstrated anti-seizure properties and reduced post-seizure hyperexcitability in neonatal mice, highlighting its drug candidate potential for treating epilepsies and other neurological diseases involving network hyperexcitability. PMID:28178321

  1. Progressive brain damage, synaptic reorganization and NMDA activation in a model of epileptogenic cortical dysplasia.

    PubMed

    Colciaghi, Francesca; Finardi, Adele; Nobili, Paola; Locatelli, Denise; Spigolon, Giada; Battaglia, Giorgio Stefano

    2014-01-01

    Whether severe epilepsy could be a progressive disorder remains as yet unresolved. We previously demonstrated in a rat model of acquired focal cortical dysplasia, the methylazoxymethanol/pilocarpine - MAM/pilocarpine - rats, that the occurrence of status epilepticus (SE) and subsequent seizures fostered a pathologic process capable of modifying the morphology of cortical pyramidal neurons and NMDA receptor expression/localization. We have here extended our analysis by evaluating neocortical and hippocampal changes in MAM/pilocarpine rats at different epilepsy stages, from few days after onset up to six months of chronic epilepsy. Our findings indicate that the process triggered by SE and subsequent seizures in the malformed brain i) is steadily progressive, deeply altering neocortical and hippocampal morphology, with atrophy of neocortex and CA regions and progressive increase of granule cell layer dispersion; ii) changes dramatically the fine morphology of neurons in neocortex and hippocampus, by increasing cell size and decreasing both dendrite arborization and spine density; iii) induces reorganization of glutamatergic and GABAergic networks in both neocortex and hippocampus, favoring excitatory vs inhibitory input; iv) activates NMDA regulatory subunits. Taken together, our data indicate that, at least in experimental models of brain malformations, severe seizure activity, i.e., SE plus recurrent seizures, may lead to a widespread, steadily progressive architectural, neuronal and synaptic reorganization in the brain. They also suggest the mechanistic relevance of glutamate/NMDA hyper-activation in the seizure-related brain pathologic plasticity.

  2. Efficacy and safety of eslicarbazepine-acetate in elderly patients with focal epilepsy: Case series.

    PubMed

    Gómez-Ibáñez, A; Serratosa, J M; Guillamón, E; Garcés, M; Giráldez, B G; Toledo, M; Salas-Puig, J; López-González, F J; Rodríguez-Uranga, J; Castillo, A; Mauri, J A; Camacho, J L; López-Gomáriz, E; Giner, P; Torres, N; Palau, J; Molins, A; Villanueva, V

    2017-05-01

    Eslicarbazepine-acetate (ESL) is a third generation antiepileptic drug licensed as adjunctive therapy in adults with focal seizures. Efficacy and safety of ESL have been established in real-life setting. However, data about outcomes in elderly patients are scarce. Primary endpoint was to evaluate outcomes of ESL in elderly patients. This was a retrospective survey that included patients >65years with focal seizures who started ESL between January 2010 and July 2012 at 12 Spanish Hospitals. ESL was prescribed individually according to real-life practice. Efficacy and safety were evaluated over 1year. These patients were included within the bigger study ESLIBASE. We included 29 patients, most of them males (18). Mean age was 71.2 year-old and epilepsy evolution was 20 years. Eighteen were pharmacorresistant at baseline. At 12 months, the mean dose was 850mg/day, the retention rate 69%, the responder rate 62% and 24.1% were seizure-free. At 12 months, 16 patients (55.2%) had ≥1 adverse effect (AE), that led to discontinuation in 7 patients. Dizziness, nausea and ataxia were the most common AEs. The tolerability profile improved in 4/5 patients who switched from carbamazepine (CBZ) or oxcarbazepine (OXC) to ESL due to AEs. ESL was well-tolerated and effective in elderly patients in a real-life setting over 1year, with a dose around 800mg/day. AE effects improved in most of who switched from CBZ or OXC to ESL. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  3. The association between tranexamic acid and convulsive seizures after cardiac surgery: a multivariate analysis in 11 529 patients.

    PubMed

    Sharma, V; Katznelson, R; Jerath, A; Garrido-Olivares, L; Carroll, J; Rao, V; Wasowicz, M; Djaiani, G

    2014-02-01

    Because of a lack of contemporary data regarding seizures after cardiac surgery, we undertook a retrospective analysis of prospectively collected data from 11 529 patients in whom cardiopulmonary bypass was used from January 2004 to December 2010. A convulsive seizure was defined as a transient episode of disturbed brain function characterised by abnormal involuntary motor movements. Multivariate regression analysis was performed to identify independent predictors of postoperative seizures. A total of 100 (0.9%) patients developed postoperative convulsive seizures. Generalised and focal seizures were identified in 68 and 32 patients, respectively. The median (IQR [range]) time after surgery when the seizure occurred was 7 (6-12 [1-216]) h and 8 (6-11 [4-18]) h, respectively. Epileptiform findings on electroencephalography were seen in 19 patients. Independent predictors of postoperative seizures included age, female sex, redo cardiac surgery, calcification of ascending aorta, congestive heart failure, deep hypothermic circulatory arrest, duration of aortic cross-clamp and tranexamic acid. When tested in a multivariate regression analysis, tranexamic acid was a strong independent predictor of seizures (OR 14.3, 95% CI 5.5-36.7; p < 0.001). Patients with convulsive seizures had 2.5 times higher in-hospital mortality rates and twice the length of hospital stay compared with patients without convulsive seizures. Mean (IQR [range]) length of stay in the intensive care unit was 115 (49-228 [32-481]) h in patients with convulsive seizures compared with 26 (22-69 [14-1080]) h in patients without seizures (p < 0.001). Convulsive seizures are a serious postoperative complication after cardiac surgery. As tranexamic acid is the only modifiable factor, its administration, particularly in doses exceeding 80 mg.kg(-1), should be weighed against the risk of postoperative seizures.

  4. A hardware-algorithm co-design approach to optimize seizure detection algorithms for implantable applications.

    PubMed

    Raghunathan, Shriram; Gupta, Sumeet K; Markandeya, Himanshu S; Roy, Kaushik; Irazoqui, Pedro P

    2010-10-30

    Implantable neural prostheses that deliver focal electrical stimulation upon demand are rapidly emerging as an alternate therapy for roughly a third of the epileptic patient population that is medically refractory. Seizure detection algorithms enable feedback mechanisms to provide focally and temporally specific intervention. Real-time feasibility and computational complexity often limit most reported detection algorithms to implementations using computers for bedside monitoring or external devices communicating with the implanted electrodes. A comparison of algorithms based on detection efficacy does not present a complete picture of the feasibility of the algorithm with limited computational power, as is the case with most battery-powered applications. We present a two-dimensional design optimization approach that takes into account both detection efficacy and hardware cost in evaluating algorithms for their feasibility in an implantable application. Detection features are first compared for their ability to detect electrographic seizures from micro-electrode data recorded from kainate-treated rats. Circuit models are then used to estimate the dynamic and leakage power consumption of the compared features. A score is assigned based on detection efficacy and the hardware cost for each of the features, then plotted on a two-dimensional design space. An optimal combination of compared features is used to construct an algorithm that provides maximal detection efficacy per unit hardware cost. The methods presented in this paper would facilitate the development of a common platform to benchmark seizure detection algorithms for comparison and feasibility analysis in the next generation of implantable neuroprosthetic devices to treat epilepsy. Copyright © 2010 Elsevier B.V. All rights reserved.

  5. Seizures, syndromes, and etiologies in childhood epilepsy: The International League Against Epilepsy 1981, 1989, and 2017 classifications used in a population-based cohort.

    PubMed

    Aaberg, Kari Modalsli; Surén, Pål; Søraas, Camilla Lund; Bakken, Inger Johanne; Lossius, Morten I; Stoltenberg, Camilla; Chin, Richard

    2017-11-01

    The study provides updated information about the distribution of seizures, epilepsies, and etiologies of epilepsy in the general child population, and compares the old and new classification systems from the International League Against Epilepsy (ILAE). The study platform was the Norwegian Mother and Child Cohort Study. Cases of epilepsy were identified through registry linkages and sequential parental questionnaires. Epilepsy diagnoses were validated using a standardized protocol, and seizures, epilepsies, and etiologies were classified according to the old (ILAE 1981/1989) and new (ILAE 2017) classifications. Information was collected through medical record reviews and/or parental telephone interviews. The study population included 112,744 children aged 3-13 years at the end of follow-up on December 31, 2012. Of these, there were 606 children with epilepsy (CWE). Distribution of seizure types varied by age of onset. Multiple seizure types were common with early onset. Focal epilepsies were the most common, occurring in 317 per 100,000 children in the study population and in 59% of CWE. Generalized epilepsies were found in 190 per 100,000 (35% of CWE). CWE with onset during the first 2 years of life had an even distribution of focal and generalized epilepsies, whereas focal epilepsies became dominant at later ages of onset. A definite cause of epilepsy had been demonstrated in 33% of CWE. The ILAE 1989 classification allowed for a broad syndrome category in 93% of CWE and a defined epileptic syndrome in 37%. With the ILAE 2017 classification, 41% of CWE had a defined epileptic syndrome and 63% had either a defined syndrome or structural-metabolic etiology. The distribution of seizures and epilepsies is strongly dependent on age of onset. Despite diagnostic advances, the causes of epilepsy are still unknown in two-thirds of CWE. The ILAE 2017 classifications allow for a higher precision of diagnoses, but at the expense of leaving more epilepsies classifiable only

  6. Acute Hippocampal Slice Preparation and Hippocampal Slice Cultures

    PubMed Central

    Lein, Pamela J.; Barnhart, Christopher D.; Pessah, Isaac N.

    2012-01-01

    A major advantage of hippocampal slice preparations is that the cytoarchitecture and synaptic circuits of the hippocampus are largely retained. In neurotoxicology research, organotypic hippocampal slices have mostly been used as acute ex vivo preparations for investigating the effects of neurotoxic chemicals on synaptic function. More recently, hippocampal slice cultures, which can be maintained for several weeks to several months in vitro, have been employed to study how neurotoxic chemicals influence the structural and functional plasticity in hippocampal neurons. This chapter provides protocols for preparing hippocampal slices to be used acutely for electrophysiological measurements using glass microelectrodes or microelectrode arrays or to be cultured for morphometric assessments of individual neurons labeled using biolistics. PMID:21815062

  7. Febrile seizures

    MedlinePlus

    ... proper care. Occasionally, a provider will prescribe a medicine called diazepam to prevent or treat febrile seizures that occur more than once. However, no drug is completely effective in preventing febrile seizures. Alternative Names Seizure - fever induced; Febrile convulsions Patient Instructions ...

  8. Seizures and Teens: Sorting Out Seizures--Part Two

    ERIC Educational Resources Information Center

    Devinsky, Orrin

    2006-01-01

    In adolescents, diagnosing seizures can be challenging and can lead to many pitfalls. Because seizures are episodic and unpredictable events, they usually do not occur in the doctor's office. Thus, a diagnosis of epilepsy is usually based on information presented by the person with seizures and their family. Together with results of diagnostic…

  9. Risk of seizure recurrence after achieving initial seizure freedom on the ketogenic diet.

    PubMed

    Taub, Katherine S; Kessler, Sudha Kilaru; Bergqvist, A G Christina

    2014-04-01

    Few studies have examined the long-term sustainability of complete seizure freedom on the ketogenic diet (KD). The purpose of this study was to describe the risk of seizure recurrence in children who achieved at least 1 month of seizure freedom on the KD, and to assess clinical features associated with sustained seizure freedom. Records of patients initiated on the KD at The Children's Hospital of Philadelphia (CHOP) from 1991 to 2009 were reviewed. Subjects who attained seizure freedom for at least 1 month within 2 years were included in the study. Seizure frequency was recorded based on caregiver-reported seizure diaries as unchanged, improved, or worse compared to baseline. Those patients with seizure freedom ≥1 year were compared to those with seizure freedom <1 year in terms of demographics, age of seizure onset, number of antiepileptic drugs (AEDs) prior to KD, and epilepsy classification. Of 276 patients initiated on the KD, 65 patients (24%) attained seizure freedom for a minimum of 1 month. The majority of these patients had daily seizures. The median time to seizure freedom after KD initiation was 1.5 months. Seizures recurred in 53 patients (82%), with a median time to seizure recurrence of 3 months. However, seizure frequency after initial recurrence remained far less than baseline. No clinical features were identified as risk factors for seizure recurrence. Seizure recurrence on the KD after 1 month of seizure freedom most often occurred as occasional breakthrough seizures and not a return to baseline seizure frequency. This study provides evidence to support the continued use of the KD in patients with initial seizure freedom even after breakthrough seizures. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

  10. Specific imbalance of excitatory/inhibitory signaling establishes seizure onset pattern in temporal lobe epilepsy

    PubMed Central

    de Curtis, Marco; Gnatkovsky, Vadym; Gotman, Jean; Köhling, Rüdiger; Lévesque, Maxime; Manseau, Frédéric; Shiri, Zahra; Williams, Sylvain

    2016-01-01

    Low-voltage fast (LVF) and hypersynchronous (HYP) patterns are the seizure-onset patterns most frequently observed in intracranial EEG recordings from mesial temporal lobe epilepsy (MTLE) patients. Both patterns also occur in models of MTLE in vivo and in vitro, and these studies have highlighted the predominant involvement of distinct neuronal network/neurotransmitter receptor signaling in each of them. First, LVF-onset seizures in epileptic rodents can originate from several limbic structures, frequently spread, and are associated with high-frequency oscillations in the ripple band (80–200 Hz), whereas HYP onset seizures initiate in the hippocampus and tend to remain focal with predominant fast ripples (250–500 Hz). Second, in vitro intracellular recordings from principal cells in limbic areas indicate that pharmacologically induced seizure-like discharges with LVF onset are initiated by a synchronous inhibitory event or by a hyperpolarizing inhibitory postsynaptic potential barrage; in contrast, HYP onset is associated with a progressive impairment of inhibition and concomitant unrestrained enhancement of excitation. Finally, in vitro optogenetic experiments show that, under comparable experimental conditions (i.e., 4-aminopyridine application), the initiation of LVF- or HYP-onset seizures depends on the preponderant involvement of interneuronal or principal cell networks, respectively. Overall, these data may provide insight to delineate better therapeutic targets in the treatment of patients presenting with MTLE and, perhaps, with other epileptic disorders as well. PMID:27075542

  11. The effectiveness of Hering's nerve stimulation in controlling penicillin-induced seizures in the rat is dependent on the amygdala.

    PubMed

    Tubbs, R Shane; Wellons, John C; Patwardhan, Ravish V; Oakes, W Jerry; Wyss, J Michael

    2002-11-01

    This study tests the hypothesis that the ability of Hering's nerve stimulation (HNS) to blunt seizure activity is dependent on the availability of dopamine in the amygdala. In 10 rats, Hering's nerve (HN) on the right side was isolated and placed on an electrode and penicillin was locally placed on each rat's left frontoparietal region to induce seizures. After the initiation of seizures, HN was stimulated. After the recurrence of seizure activity, the left basolateral amygdala was injected with 1.0 microl of normal saline, dopamine, haloperidol or 1% lidocaine in sequential tests. HN was stimulated after each injection and the latency and amplitude of the seizure activity were assessed. Focal cortical penicillin induced seizures that resulted in tonic-clonic movement of the limbs and face that lasted 35-45 min. Tonic-clonic movements of the limbs and face of similar latency and amplitude were induced by repeated reapplication of penicillin in untreated rats. HNS decreased seizure activity, but infusion of haloperidol or lidocaine into the basolateral amygdala blocked this antiseizure effect of HNS. In contrast, infusion of saline or dopamine had no effect on the ability of HNS to blunt seizure activity. None of the amygdala injections altered the latency or amplitude of seizure activity. These results demonstrate that the ability of HNS to blunt seizure activity in the rat is dependent on an intact dopamine system in the basolateral amygdala. These data will hopefully be useful in furthering our understanding of the circuitry that allows peripheral nerve stimulation to alter seizure activity. Copyright 2002 S. Karger AG, Basel

  12. Individualised prediction model of seizure recurrence and long-term outcomes after withdrawal of antiepileptic drugs in seizure-free patients: a systematic review and individual participant data meta-analysis.

    PubMed

    Lamberink, Herm J; Otte, Willem M; Geerts, Ada T; Pavlovic, Milen; Ramos-Lizana, Julio; Marson, Anthony G; Overweg, Jan; Sauma, Letícia; Specchio, Luigi M; Tennison, Michael; Cardoso, Tania M O; Shinnar, Shlomo; Schmidt, Dieter; Geleijns, Karin; Braun, Kees P J

    2017-07-01

    epilepsy duration before remission, seizure-free interval before antiepileptic drug withdrawal, age at onset of epilepsy, history of febrile seizures, number of seizures before remission, absence of a self-limiting epilepsy syndrome, developmental delay, and epileptiform abnormality on electroencephalogram (EEG) before withdrawal. Independent predictors of seizures in the last year of follow-up were epilepsy duration before remission, seizure-free interval before antiepileptic drug withdrawal, number of antiepileptic drugs before withdrawal, female sex, family history of epilepsy, number of seizures before remission, focal seizures, and epileptiform abnormality on EEG before withdrawal. Adjusted concordance statistics were 0·65 (95% CI 0·65-0·66) for predicting seizure recurrence and 0·71 (0·70-0·71) for predicting long-term seizure freedom. Validation was stable across the individual study populations. We present evidence-based nomograms with robust performance across populations of children and adults. The nomograms facilitate prediction of outcomes following drug withdrawal for the individual patient, including both the risk of relapse and the chance of long-term freedom from seizures. The main limitations were the absence of a control group continuing antiepileptic drug treatment and a consistent definition of long-term seizure freedom. Epilepsiefonds. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Non-EEG seizure detection systems and potential SUDEP prevention: State of the art: Review and update.

    PubMed

    Van de Vel, Anouk; Cuppens, Kris; Bonroy, Bert; Milosevic, Milica; Jansen, Katrien; Van Huffel, Sabine; Vanrumste, Bart; Cras, Patrick; Lagae, Lieven; Ceulemans, Berten

    2016-10-01

    Detection of, and alarming for epileptic seizures is increasingly demanded and researched. Our previous review article provided an overview of non-invasive, non-EEG (electro-encephalography) body signals that can be measured, along with corresponding methods, state of the art research, and commercially available systems. Three years later, many more studies and devices have emerged. Moreover, the boom of smart phones and tablets created a new market for seizure detection applications. We performed a thorough literature review and had contact with manufacturers of commercially available devices. This review article gives an updated overview of body signals and methods for seizure detection, international research and (commercially) available systems and applications. Reported results of non-EEG based detection devices vary between 2.2% and 100% sensitivity and between 0 and 3.23 false detections per hour compared to the gold standard video-EEG, for seizures ranging from generalized to convulsive or non-convulsive focal seizures with or without loss of consciousness. It is particularly interesting to include monitoring of autonomic dysfunction, as this may be an important pathophysiological mechanism of SUDEP (sudden unexpected death in epilepsy), and of movement, as many seizures have a motor component. Comparison of research results is difficult as studies focus on different seizure types, timing (night versus day) and patients (adult versus pediatric patients). Nevertheless, we are convinced that the most effective seizure detection systems are multimodal, combining for example detection methods for movement and heart rate, and that devices should especially take into account the user's seizure types and personal preferences. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  14. Automated seizure detection systems and their effectiveness for each type of seizure.

    PubMed

    Ulate-Campos, A; Coughlin, F; Gaínza-Lein, M; Fernández, I Sánchez; Pearl, P L; Loddenkemper, T

    2016-08-01

    Epilepsy affects almost 1% of the population and most of the approximately 20-30% of patients with refractory epilepsy have one or more seizures per month. Seizure detection devices allow an objective assessment of seizure frequency and a treatment tailored to the individual patient. A rapid recognition and treatment of seizures through closed-loop systems could potentially decrease morbidity and mortality in epilepsy. However, no single detection device can detect all seizure types. Therefore, the choice of a seizure detection device should consider the patient-specific seizure semiologies. This review of the literature evaluates seizure detection devices and their effectiveness for different seizure types. Our aim is to summarize current evidence, offer suggestions on how to select the most suitable seizure detection device for each patient and provide guidance to physicians, families and researchers when choosing or designing seizure detection devices. Further, this review will guide future prospective validation studies. Copyright © 2016. Published by Elsevier Ltd.

  15. The Subiculum: A Potential Site of Ictogenesis in a Neonatal Seizure Model

    PubMed Central

    Wang, Xin-Xin; Li, Yong-Hua; Gong, Hai-Qing; Liang, Pei-Ji; Zhang, Pu-Ming; Lu, Qin-Chi

    2017-01-01

    Studies have reported that the subiculum is one origin of interictal-like discharges in adult patients with temporal lobe epilepsy; however, whether the subiculum represents a site of ictogenesis for neonatal seizures remains unclear. In this study, multi-electrode recording techniques were used to record epileptiform discharges induced by low-Mg2+ or high-K+ artificial cerebrospinal fluid in neonatal mouse hippocampal slices, and the spatiotemporal dynamics of the epileptiform discharges were analyzed. The Na+–K+–2Cl− cotransporter 1 (NKCC1) blocker, bumetanide, was applied to test its effect upon epileptiform discharges in low-Mg2+ model. The effect of N-methyl-d-aspartate receptors (NMDARs) antagonist, d-AP5, upon the epileptiform discharges in high-K+ model was examined. We found that the neonatal subiculum not only relayed epileptiform discharges emanating from the hippocampus proper (HP) but also initiated epileptiform discharges (interictal- and ictal-like discharges) independently. The latency to onset of the first epileptiform discharge initiated in the subiculum was similar to that initiated in the HP. Bumetanide efficiently blocked seizures in the neonatal HP, but was less effectively in suppressing seizures initiated in the subiculum. In high-K+ model, d-AP5 was more effective in blocking seizures initiated in the subiculum than that initiated in the HP. Furthermore, Western blotting analysis showed that NKCC1 expression was lower in the subiculum than that in the HP, whereas the expression of NMDAR subunits, NR2A and NR2B, was higher in the subiculum than that in the HP. Our results revealed that the subiculum was a potential site of ictogenesis in neonatal seizures and possessed similar seizure susceptibility to the HP. GABAergic excitation resulting from NKCC1 may play a less dominant role during ictogenesis in the subiculum than that in the HP. The subicular ictogenesis may be related to the glutamatergic excitation mediated by NMDARs. PMID

  16. The role of the GLP-1/GLP-1R signaling pathway in regulating seizure susceptibility in rats.

    PubMed

    Zhang, Yusong; Fang, Jian; Feng, Wen; Sun, Qi; Xu, Jian; Xia, Qingxin

    2018-06-27

    This study aimed to investigate the role of glucagon-like peptide-1 (GLP-1)/GLP-1 receptor(R) signaling in the regulation of seizure susceptibility and to explore the potential mechanism in rats. Hyperthermia-induced seizures in SD rats were generated using hot bath methods, and seizure severity was measured according to Racine scores and electroencephalogram (EEG). Protein levels of GLP-1 and GLP-1R in the brain tissues of rats were evaluated through ELISA, western blot analysis, and immunohistochemistry to explore the possible roles of each in FS. Neuronal excitability, spontaneous inhibitory postsynaptic currents (sIPSCs) and transient receptor potential cation channel subfamily V member 1(TRPV1) currents were tested using the patch-clamp method in cultured hippocampal neurons. Significant decreases in the levels of GLP-1 and GLP-1R were observed in the hippocampi of rats compared to those in the control group. Furthermore, treatment with the GLP-1R pharmacological inhibitor exendin9-39 increased hyperthermia- induced seizure severity in rats and promoted neuronal firing activity in cultured neurons. Importantly, exendin9-39 and GLP-1R knockdown decreased the amplitude and frequency of sIPSCs in cultured neurons. In addition, GLP-1R knockdown elevated downstream TRPV1 expression and promoted capsaicin-induced TRPV1 function, which may regulate inhibitory neurotransmission to affect seizure susceptibility. The present study suggests that inhibition of GLP-1R signaling promotes seizure activity, which plays a key role in the pathogenesis of FS. Copyright © 2018. Published by Elsevier Inc.

  17. Laboratory findings in neurosyphilis patients with epileptic seizures alone as the initial presenting symptom.

    PubMed

    Tong, Man-Li; Liu, Li-Li; Zeng, Yan-Li; Zhang, Hui-Lin; Liu, Gui-Li; Zheng, Wei-Hong; Dong, Jie; Wu, Jing-Yi; Su, Yuan-Hui; Lin, Li-Rong; Yang, Tian-Ci

    2013-04-01

    A retrospective chart review was performed to characterize the clinical presentation, the characteristic combination of serologic and cerebrospinal fluid (CSF) abnormalities, and the neuroimaging findings of neurosyphilis (NS) patients who had epileptic seizures alone as an initial presenting symptom. In a 6.75-year period, 169 inpatients with NS were identified at Zhongshan Hospital (from June 2005 to February 2012). We demonstrated that 13 (7.7%) of the 169 NS patients had epileptic seizures alone as an initial presenting feature. Epileptic seizures occurred in NS patients with syphilitic meningitis (2 cases), meningovascular NS (5 cases), and general paresis (6 cases). The types of epileptic seizures included simple partial, complex partial with secondary generalization (including status epilepticus), and generalized seizures (no focal onset reported). Nine of NS patients with only epileptic seizures as primary symptom were misdiagnosed, and the original misdiagnosis was 69.23% (9/13). Ten (10/13, 76.9%) patients had an abnormal magnetic resonance imaging, and 7 (7/13 53.8%) patients had abnormal electroencephalogram recordings. In addition, the sera rapid plasma reagin (RPR) and Treponema pallidum particle agglutination (TPPA) from all 13 patients were positive. The overall positive rates of the CSF-RPR and CSF-TPPA were 61.5% and 69.2%, respectively. Three patients demonstrated CSF pleocytosis, and 9 patients exhibited elevated CSF protein levels. Therefore, NS with only epileptic seizures at the initial presentation exhibits a lack of specificity. It is recommended that every patient with clinically evident symptoms of epileptic seizures should have a blood test performed for syphilis. When the serology results are positive, all of the patients should undergo a CSF examination to diagnose NS. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Imaging of patients with hippocampal sclerosis at 7 Tesla: initial results.

    PubMed

    Breyer, Tobias; Wanke, Isabel; Maderwald, Stefan; Woermann, Friedrich G; Kraff, Oliver; Theysohn, Jens M; Ebner, Alois; Forsting, Michael; Ladd, Mark E; Schlamann, Marc

    2010-04-01

    Focal epilepsies potentially can be cured by neurosurgery; other treatment options usually remain symptomatic. High-resolution magnetic resonance (MR) imaging is the central imaging strategy in the evaluation of focal epilepsy. The most common substrate of temporal epilepsies is hippocampal sclerosis (HS), which cannot always be sufficiently characterized with current MR field strengths. Therefore, the purpose of our study was to demonstrate the feasibility of high-resolution MR imaging at 7 Tesla in patients with focal epilepsy resulting from a HS and to improve image resolution at 7 Tesla in patients with HS. Six patients with known HS were investigated with T1-, T2-, T2(*)-, and fluid-attenuated inversion recovery-weighted sequences at 7 Tesla with an eight-channel transmit-receive head coil. Total imaging time did not exceed 90 minutes per patient. High-resolution imaging at 7 Tesla is feasible and reveals high resolution of intrahippocampal structures in vivo. HS was confirmed in all patients. The maximum non-interpolated in-plane resolution reached 0.2 x 0.2 mm(2) in T2(*)-weighted images. The increased susceptibility effects at 7 Tesla revealed identification of intrahippocampal structures in more detail than at 1.5 Tesla, but otherwise led to stronger artifacts. Imaging revealed regional differences in hippocampal atrophy between patients. The scan volume was limited because of specific absorption rate restrictions, scanning time was reasonable. High-resolution imaging at 7 Tesla is promising in presurgical epilepsy imaging. "New" contrasts may further improve detection of even very small intrahippocampal structural changes. Therefore, further investigations will be necessary to demonstrate the potential benefit for presurgical selection of patients with various lesion patterns in mesial temporal epilepsies resulting from a unilateral HS. Copyright 2010 AUR. Published by Elsevier Inc. All rights reserved.

  19. The temporal relation between seizure onset and arousal-awakening in temporal lobe seizures.

    PubMed

    Gumusyayla, Sadiye; Erdal, Abidin; Tezer, F Irsel; Saygi, Serap

    2016-07-01

    Our main aim was to determine the time interval between the seizure onsets and arousal-awakening related to these seizures in patients with temporal lobe epilepsy (TLE) and to discuss the role of lateralization on arousal-awakening mechanisms. Thirty-three TLE patients who underwent video-EEG monitoring with simultaneous polysomnography (PSG) and had recorded nocturnal seizures were retrospectively examined. These TLE patients had 64 seizures during sleep. The onsets of seizures and arousal-awakening related to these seizures were marked according to clinical and electrophysiological features. The time interval between the seizure onset and arousal-awakening related to the seizure was compared in patients with right- or left-sided temporal lobe seizures. In our TLE patients nocturnal seizures mostly followed arousal-awakening (64%). The time interval between the seizure onset and arousal-awakening related to the seizure was significantly shorter in patients with left-sided temporal lobe seizures (p=0.01). Video-EEG monitoring and PSG with scalp electrodes in our TLE patients showed that nocturnal seizures mostly followed arousal-awakening, and it was more pronounced in those with left-sided seizures. Arousal-awakening might be a signal for subsequent seizures in patients with TLE. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  20. Stimulation Induced Electrographic Seizures in Deep Brain Stimulation of the Anterior Nucleus of the Thalamus Do Not Preclude a Subsequent Favorable Treatment Response.

    PubMed

    Nora, Tommi; Heinonen, Hanna; Tenhunen, Mirja; Rainesalo, Sirpa; Järvenpää, Soila; Lehtimäki, Kai; Peltola, Jukka

    2018-01-01

    Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is a method of neuromodulation used for refractory focal epilepsy. We report a patient suffering from drug-resistant epilepsy who developed novel visual symptoms and atypical seizures with the onset of ANT-DBS therapy. Rechallenge under video electroencephalography recording confirmed that lowering the stimulation voltage alleviated these symptoms. Subsequent stimulation with the initial voltage value did not cause the recurrence of either the visual symptoms or the new seizure type, and appeared to alleviate the patient's seizures in long-term follow-up. We therefore hypothesize that the occurrence of stimulation induced seizures at the onset of DBS therapy should not be considered as a failure in the DBS therapy, and the possibility of a subsequent favorable response to the treatment still exists.

  1. Okadaic acid induces epileptic seizures and hyperphosphorylation of the NR2B subunit of the NMDA receptor in rat hippocampus in vivo.

    PubMed

    Arias, Clorinda; Montiel, Teresa; Peña, Fernando; Ferrera, Patricia; Tapia, Ricardo

    2002-09-01

    Overactivation of N-methyl-D-aspartate (NMDA) glutamate receptors is closely related to epilepsy and excitotoxicity, and the phosphorylation of these receptors may facilitate glutamate-mediated synaptic transmission. Here we show that in awake rats the microinjection into the hippocampus of okadaic acid, a potent inhibitor of protein phosphatases 1 and 2A, induces in about 20 min intense electroencephalographic and behavioral limbic-type seizures, which are suppressed by the systemic administration of the NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo-[a,d]cyclohepten-5,10-imine hydrogen maleate and by the intrahippocampal administration of 1-(5-isoquinolinesulfonyl)-2-methylpiperazine, an inhibitor of protein kinases. Two hours after okadaic acid, when the EEG seizures were intense, an increased serine phosphorylation of some hippocampal proteins, including an enhancement of the serine phosphorylation of the NMDA receptor subunit NR2B, was detected by immunoblotting. Twenty-four hours after okadaic acid a marked destruction of hippocampal CA1 region was observed, which was not prevented by the receptor antagonists. These findings suggest that hyperphosphorylation of glutamate receptors in vivo may result in an increased sensitivity to the endogenous transmitter and therefore induce neuronal hyperexcitability and epilepsy.

  2. Eight Flurothyl-Induced Generalized Seizures Lead to the Rapid Evolution of Spontaneous Seizures in Mice: A Model of Epileptogenesis with Seizure Remission.

    PubMed

    Kadiyala, Sridhar B; Yannix, Joshua Q; Nalwalk, Julia W; Papandrea, Dominick; Beyer, Barbara S; Herron, Bruce J; Ferland, Russell J

    2016-07-13

    The occurrence of recurrent, unprovoked seizures is the hallmark of human epilepsy. Currently, only two-thirds of this patient population has adequate seizure control. New epilepsy models provide the potential for not only understanding the development of spontaneous seizures, but also for testing new strategies to treat this disorder. Here, we characterize a primary generalized seizure model of epilepsy following repeated exposure to the GABAA receptor antagonist, flurothyl, in which mice develop spontaneous seizures that remit within 1 month. In this model, we expose C57BL/6J mice to flurothyl until they experience a generalized seizure. Each of these generalized seizures typically lasts <30 s. We induce one seizure per day for 8 d followed by 24 h video-electroencephalographic recordings. Within 1 d following the last of eight flurothyl-induced seizures, ∼50% of mice have spontaneous seizures. Ninety-five percent of mice tested have seizures within the first week of the recording period. Of the spontaneous seizures recorded, the majority are generalized clonic seizures, with the remaining 7-12% comprising generalized clonic seizures that transition into brainstem seizures. Over the course of an 8 week recording period, spontaneous seizure episodes remit after ∼4 weeks. Overall, the repeated flurothyl paradigm is a model of epileptogenesis with spontaneous seizures that remit. This model provides an additional tool in our armamentarium for understanding the mechanisms underlying epileptogenesis and may provide insights into why spontaneous seizures remit without anticonvulsant treatment. Elucidating these processes could lead to the development of new epilepsy therapeutics. Epilepsy is a chronic disorder characterized by the occurrence of recurrent, unprovoked seizures in which the individual seizure-ictal events are self-limiting. Remission of recurrent, unprovoked seizures can be achieved in two-thirds of cases by treatment with anticonvulsant medication

  3. Acute seizure suppression by transcranial direct current stimulation in rats

    PubMed Central

    Dhamne, Sameer C; Ekstein, Dana; Zhuo, Zhihong; Gersner, Roman; Zurakowski, David; Loddenkemper, Tobias; Pascual-Leone, Alvaro; Jensen, Frances E; Rotenberg, Alexander

    2015-01-01

    Objective Cathodal transcranial direct current stimulation (tDCS) is a focal neuromodulation technique that suppresses cortical excitability by low-amplitude constant electrical current, and may have an antiepileptic effect. Yet, tDCS has not been tested in status epilepticus (SE). Furthermore, a combined tDCS and pharmacotherapy antiseizure approach is unexplored. We therefore examined in the rat pentylenetetrazol (PTZ) SE model whether cathodal tDCS (1) suppresses seizures, (2) augments lorazepam (LZP) efficacy, and (3) enhances GABAergic cortical inhibition. Methods Experiment 1 aimed to identify an effective cathodal tDCS intensity. Rats received intraperitoneal PTZ followed by tDCS (sham, cathodal 1 mA, or cathodal 0.1 mA; for 20 min), and then a second PTZ challenge. In Experiment 2, two additional animal groups received a subtherapeutic LZP dose after PTZ, and then verum or sham tDCS. Clinical and electroencephalography (EEG) epileptic activity were compared between all groups. In Experiment 3, we measured GABA-mediated paired-pulse inhibition of the motor evoked potential by paired-pulse transcranial magnetic stimulation (ppTMS) in rats that received PTZ or saline, and either verum or sham tDCS. Results Cathodal 1 mA tDCS (1) reduced EEG spike bursts, and suppressed clinical seizures after the second PTZ challenge, (2) in combination with LZP was more effective in seizure suppression and improved the clinical seizure outcomes compared to either tDCS or LZP alone, and (3) prevented the loss of ppTMS motor cortex inhibition that accompanied PTZ injection. Interpretation These results suggest that cathodal 1 mA tDCS alone and in combination with LZP can suppress seizures by augmenting GABAergic cortical inhibition. PMID:26339678

  4. Loss of Hippocampal Neurons after Kainate Treatment Correlates with Behavioral Deficits

    PubMed Central

    Maia, Gisela H.; Quesado, José L.; Soares, Joana I.; do Carmo, Joana M.; Andrade, Pedro A.; Andrade, José P.; Lukoyanov, Nikolai V.

    2014-01-01

    Treating rats with kainic acid induces status epilepticus (SE) and leads to the development of behavioral deficits and spontaneous recurrent seizures later in life. However, in a subset of rats, kainic acid treatment does not induce overt behaviorally obvious acute SE. The goal of this study was to compare the neuroanatomical and behavioral changes induced by kainate in rats that developed convulsive SE to those who did not. Adult male Wistar rats were treated with kainic acid and tested behaviorally 5 months later. Rats that had experienced convulsive SE showed impaired performance on the spatial water maze and passive avoidance tasks, and on the context and tone retention tests following fear conditioning. In addition, they exhibited less anxiety-like behaviors than controls on the open-field and elevated plus-maze tests. Histologically, convulsive SE was associated with marked neuron loss in the hippocampal CA3 and CA1 fields, and in the dentate hilus. Rats that had not experienced convulsive SE after kainate treatment showed less severe, but significant impairments on the spatial water maze and passive avoidance tasks. These rats had fewer neurons than control rats in the dentate hilus, but not in the hippocampal CA3 and CA1 fields. Correlational analyses revealed significant relationships between spatial memory indices of rats and neuronal numbers in the dentate hilus and CA3 pyramidal field. These results show that a part of the animals that do not display intense behavioral seizures (convulsive SE) immediately after an epileptogenic treatment, later in life, they may still have noticeable structural and functional changes in the brain. PMID:24409306

  5. Histological Characterization of the Irritative Zones in Focal Cortical Dysplasia Using a Preclinical Rat Model.

    PubMed

    Deshmukh, Abhay; Leichner, Jared; Bae, Jihye; Song, Yinchen; Valdés-Hernández, Pedro A; Lin, Wei-Chiang; Riera, Jorge J

    2018-01-01

    Current clinical practice in focal epilepsy involves brain source imaging (BSI) to localize brain areas where from interictal epileptiform discharges (IEDs) emerge. These areas, named irritative zones , have been useful to define candidate seizures-onset zones during pre-surgical workup. Since human histological data are mostly available from final resected zones, systematic studies characterizing pathophysiological mechanisms and abnormal molecular/cellular substrates in irritative zones-independent of them being epileptogenic-are challenging. Combining BSI and histological analysis from all types of irritative zones is only possible through the use of preclinical animal models. Here, we recorded 32-channel spontaneous electroencephalographic data from rats that have focal cortical dysplasia (FCD) and chronic seizures. BSI for different IED subtypes was performed using the methodology presented in Bae et al. (2015). Post-mortem brain sections containing irritative zones were stained to quantify anatomical, functional, and inflammatory biomarkers specific for epileptogenesis, and the results were compared with those obtained using the contralateral healthy brain tissue. We found abnormal anatomical structures in all irritative zones (i.e., larger neuronal processes, glioreactivity, and vascular cuffing) and larger expressions for neurotransmission (i.e., NR2B) and inflammation (i.e., ILβ1, TNFα and HMGB1). We conclude that irritative zones in this rat preclinical model of FCD comprise abnormal tissues disregarding whether they are actually involved in icto-genesis or not. We hypothesize that seizure perpetuation happens gradually; hence, our results could support the use of IED-based BSI for the early diagnosis and preventive treatment of potential epileptic foci. Further verifications in humans are yet needed.

  6. Information theoretic measures of network coordination in high-frequency scalp EEG reveal dynamic patterns associated with seizure termination

    PubMed Central

    Stamoulis, Catherine; Schomer, Donald L.; Chang, Bernard S.

    2013-01-01

    How a seizure terminates is still under-studied and, despite its clinical importance, remains an obscure phase of seizure evolution. Recent studies of seizure-related scalp EEGs at frequencies >100 Hz suggest that neural activity, in the form of oscillations and/or neuronal network interactions, may play an important role in preictal/ictal seizure evolution [2, 31]. However, the role of high-frequency activity in seizure termination, is unknown, if it exists at all. Using information theoretic measures of network coordination, this study investigated ictal and immediate postictal neurodynamic interactions encoded in scalp EEGs from a relatively small sample of 8 patients with focal epilepsy and multiple seizures originating in temporal and/or frontal brain regions, at frequencies ≤100 Hz and >100 Hz, respectively. Despite some heterogeneity in the dynamics of these interactions, consistent patterns were also estimated. Specifically, in several seizures, linear or non-linear increase in high-frequency neuronal coordination during ictal intervals, coincided with a corresponding decrease in coordination at frequencies <100 Hz, suggesting a potential interference role of high-frequency activity, to disrupt abnormal ictal synchrony at lower frequencies. These changes in network synchrony started at least 20–30 sec prior to seizure offset, depending on the seizure duration. Opposite patterns were estimated at frequencies ≤100 Hz in several seizures. These results raise the possibility that high-frequency interference may occur in the form of progressive network coordination during the ictal interval, which continues during the postictal interval. This may be one of several possible mechanisms that facilitate seizure termination. In fact, inhibition of pairwise interactions between EEGs by other signals in their spatial neighborhood, quantified by negative interaction information, was estimated at frequencies ≤100 Hz, at least in some seizures. PMID:23608198

  7. Information theoretic measures of network coordination in high-frequency scalp EEG reveal dynamic patterns associated with seizure termination.

    PubMed

    Stamoulis, Catherine; Schomer, Donald L; Chang, Bernard S

    2013-08-01

    How a seizure terminates is still under-studied and, despite its clinical importance, remains an obscure phase of seizure evolution. Recent studies of seizure-related scalp EEGs at frequencies >100 Hz suggest that neural activity, in the form of oscillations and/or neuronal network interactions, may play an important role in preictal/ictal seizure evolution (Andrade-Valenca et al., 2011; Stamoulis et al., 2012). However, the role of high-frequency activity in seizure termination, is unknown, if it exists at all. Using information theoretic measures of network coordination, this study investigated ictal and immediate postictal neurodynamic interactions encoded in scalp EEGs from a relatively small sample of 8 patients with focal epilepsy and multiple seizures originating in temporal and/or frontal brain regions, at frequencies ≤ 100 Hz and >100 Hz, respectively. Despite some heterogeneity in the dynamics of these interactions, consistent patterns were also estimated. Specifically, in several seizures, linear or non-linear increase in high-frequency neuronal coordination during ictal intervals, coincided with a corresponding decrease in coordination at frequencies <100 Hz, suggesting a potential interference role of high-frequency activity, to disrupt abnormal ictal synchrony at lower frequencies. These changes in network synchrony started at least 20-30s prior to seizure offset, depending on the seizure duration. Opposite patterns were estimated at frequencies ≤ 100 Hz in several seizures. These results raise the possibility that high-frequency interference may occur in the form of progressive network coordination during the ictal interval, which continues during the postictal interval. This may be one of several possible mechanisms that facilitate seizure termination. In fact, inhibition of pairwise interactions between EEGs by other signals in their spatial neighborhood, quantified by negative interaction information, was estimated at frequencies ≤ 100 Hz

  8. Risk factors of postictal generalized EEG suppression in generalized convulsive seizures.

    PubMed

    Alexandre, Veriano; Mercedes, Blanca; Valton, Luc; Maillard, Louis; Bartolomei, Fabrice; Szurhaj, William; Hirsch, Edouard; Marchal, Cécile; Chassoux, Francine; Petit, Jérôme; Crespel, Arielle; Nica, Anca; Navarro, Vincent; Kahane, Philippe; De Toffol, Bertrand; Thomas, Pierre; Rosenberg, Sarah; Denuelle, Marie; Jonas, Jacques; Ryvlin, Philippe; Rheims, Sylvain

    2015-11-03

    To identify the clinical determinants of occurrence of postictal generalized EEG suppression (PGES) after generalized convulsive seizures (GCS). We reviewed the video-EEG recordings of 417 patients included in the REPO2MSE study, a multicenter prospective cohort study of patients with drug-resistant focal epilepsy. According to ictal semiology, we classified GCS into 3 types: tonic-clonic GCS with bilateral and symmetric tonic arm extension (type 1), clonic GCS without tonic arm extension or flexion (type 2), and GCS with unilateral or asymmetric tonic arm extension or flexion (type 3). Association between PGES and person-specific or seizure-specific variables was analyzed after correction for individual effects and the varying number of seizures. A total of 99 GCS in 69 patients were included. Occurrence of PGES was independently associated with GCS type (p < 0.001) and lack of early administration of oxygen (p < 0.001). Odds ratio (OR) for GCS type 1 in comparison with GCS type 2 was 66.0 (95% confidence interval [CI 5.4-801.6]). In GCS type 1, risk of PGES was significantly increased when the seizure occurred during sleep (OR 5.0, 95% CI 1.2-20.9) and when oxygen was not administered early (OR 13.4, 95% CI 3.2-55.9). The risk of PGES dramatically varied as a function of GCS semiologic characteristics. Whatever the type of GCS, occurrence of PGES was prevented by early administration of oxygen. © 2015 American Academy of Neurology.

  9. Eight Flurothyl-Induced Generalized Seizures Lead to the Rapid Evolution of Spontaneous Seizures in Mice: A Model of Epileptogenesis with Seizure Remission

    PubMed Central

    Kadiyala, Sridhar B.; Yannix, Joshua Q.; Nalwalk, Julia W.; Papandrea, Dominick; Beyer, Barbara S.; Herron, Bruce J.

    2016-01-01

    The occurrence of recurrent, unprovoked seizures is the hallmark of human epilepsy. Currently, only two-thirds of this patient population has adequate seizure control. New epilepsy models provide the potential for not only understanding the development of spontaneous seizures, but also for testing new strategies to treat this disorder. Here, we characterize a primary generalized seizure model of epilepsy following repeated exposure to the GABAA receptor antagonist, flurothyl, in which mice develop spontaneous seizures that remit within 1 month. In this model, we expose C57BL/6J mice to flurothyl until they experience a generalized seizure. Each of these generalized seizures typically lasts <30 s. We induce one seizure per day for 8 d followed by 24 h video-electroencephalographic recordings. Within 1 d following the last of eight flurothyl-induced seizures, ∼50% of mice have spontaneous seizures. Ninety-five percent of mice tested have seizures within the first week of the recording period. Of the spontaneous seizures recorded, the majority are generalized clonic seizures, with the remaining 7–12% comprising generalized clonic seizures that transition into brainstem seizures. Over the course of an 8 week recording period, spontaneous seizure episodes remit after ∼4 weeks. Overall, the repeated flurothyl paradigm is a model of epileptogenesis with spontaneous seizures that remit. This model provides an additional tool in our armamentarium for understanding the mechanisms underlying epileptogenesis and may provide insights into why spontaneous seizures remit without anticonvulsant treatment. Elucidating these processes could lead to the development of new epilepsy therapeutics. SIGNIFICANCE STATEMENT Epilepsy is a chronic disorder characterized by the occurrence of recurrent, unprovoked seizures in which the individual seizure–ictal events are self-limiting. Remission of recurrent, unprovoked seizures can be achieved in two-thirds of cases by treatment with

  10. Seizures

    MedlinePlus

    ... wake up between them. Seizures can have many causes, including medicines, high fevers, head injuries and certain diseases. People who have recurring seizures due to a brain disorder have epilepsy. NIH: National Institute of Neurological Disorders and Stroke

  11. Semiology of psychogenic nonepileptic seizures: An international cross-cultural study.

    PubMed

    Asadi-Pooya, Ali A; Valente, Kette; Alessi, Ruda; Tinker, Jennifer

    2017-10-01

    We compared the semiology of psychogenic nonepileptic seizures (PNES) between patients from the USA and Brazil. This international cross-cultural comparative study may expand understanding of PNES across the borders. We retrospectively investigated all patients with PNES admitted to one epilepsy center in the USA and one in Brazil. We classified their seizures into four classes: generalized motor, akinetic, focal motor, and subjective symptoms. All patients were interviewed by an epileptologist in both countries and were administered psychological assessment measures, including questions about PNES risk factors. For the statistical analyses, we compared patients from the two nations. Eighty-nine patients (49 from the USA and 40 from Brazil) were studied. Patients from the two countries were not significantly different with regard to sex and age, but patients from Brazil had earlier age at onset (26years vs. 34years; P=0.004) and a significantly greater delay in diagnosis (9.9years vs. 5.6years; P=0.001). Some characteristics of PNES were different between the two groups; patients from the USA had generally more seizure types and more often reported subjective seizures (55% in the USA vs. 10% in Brazil; P=0.0001). Clinical and historical characteristics of the patients were not significantly different. Delay in diagnosis of PNES may represent a major factor in resource-limited countries. Large multicenter cross-cultural studies may reveal subtle but significant cross-cultural differences with respect to the semiological, clinical, and historical aspects of PNES; however, patients with PNES share more similarities than differences. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Integrating artificial intelligence with real-time intracranial EEG monitoring to automate interictal identification of seizure onset zones in focal epilepsy.

    PubMed

    Varatharajah, Yogatheesan; Berry, Brent; Cimbalnik, Jan; Kremen, Vaclav; Van Gompel, Jamie; Stead, Matt; Brinkmann, Benjamin; Iyer, Ravishankar; Worrell, Gregory

    2018-08-01

    An ability to map seizure-generating brain tissue, i.e. the seizure onset zone (SOZ), without recording actual seizures could reduce the duration of invasive EEG monitoring for patients with drug-resistant epilepsy. A widely-adopted practice in the literature is to compare the incidence (events/time) of putative pathological electrophysiological biomarkers associated with epileptic brain tissue with the SOZ determined from spontaneous seizures recorded with intracranial EEG, primarily using a single biomarker. Clinical translation of the previous efforts suffers from their inability to generalize across multiple patients because of (a) the inter-patient variability and (b) the temporal variability in the epileptogenic activity. Here, we report an artificial intelligence-based approach for combining multiple interictal electrophysiological biomarkers and their temporal characteristics as a way of accounting for the above barriers and show that it can reliably identify seizure onset zones in a study cohort of 82 patients who underwent evaluation for drug-resistant epilepsy. Our investigation provides evidence that utilizing the complementary information provided by multiple electrophysiological biomarkers and their temporal characteristics can significantly improve the localization potential compared to previously published single-biomarker incidence-based approaches, resulting in an average area under ROC curve (AUC) value of 0.73 in a cohort of 82 patients. Our results also suggest that recording durations between 90 min and 2 h are sufficient to localize SOZs with accuracies that may prove clinically relevant. The successful validation of our approach on a large cohort of 82 patients warrants future investigation on the feasibility of utilizing intra-operative EEG monitoring and artificial intelligence to localize epileptogenic brain tissue. Broadly, our study demonstrates the use of artificial intelligence coupled with careful feature engineering in

  13. Deep Recurrent Neural Networks for seizure detection and early seizure detection systems

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Talathi, S. S.

    Epilepsy is common neurological diseases, affecting about 0.6-0.8 % of world population. Epileptic patients suffer from chronic unprovoked seizures, which can result in broad spectrum of debilitating medical and social consequences. Since seizures, in general, occur infrequently and are unpredictable, automated seizure detection systems are recommended to screen for seizures during long-term electroencephalogram (EEG) recordings. In addition, systems for early seizure detection can lead to the development of new types of intervention systems that are designed to control or shorten the duration of seizure events. In this article, we investigate the utility of recurrent neural networks (RNNs) in designing seizuremore » detection and early seizure detection systems. We propose a deep learning framework via the use of Gated Recurrent Unit (GRU) RNNs for seizure detection. We use publicly available data in order to evaluate our method and demonstrate very promising evaluation results with overall accuracy close to 100 %. We also systematically investigate the application of our method for early seizure warning systems. Our method can detect about 98% of seizure events within the first 5 seconds of the overall epileptic seizure duration.« less

  14. System characterization of neuronal excitability in the hippocampus and its relevance to observed dynamics of spontaneous seizure-like transitions.

    PubMed

    Zalay, Osbert C; Serletis, Demitre; Carlen, Peter L; Bardakjian, Berj L

    2010-06-01

    Most forms of epilepsy are marked by seizure episodes that arise spontaneously. The low-magnesium/high-potassium (low-Mg(2+)/high-K(+)) experimental model of epilepsy is an acute model that produces spontaneous, recurring seizure-like events (SLEs). To elucidate the nature of spontaneous seizure transitions and their relationship to neuronal excitability, whole-cell recordings from the intact hippocampus were undertaken in vitro, and the response of hippocampal CA3 neurons to Gaussian white noise injection was obtained before and after treatment with various concentrations of low-Mg(2+)/high-K(+) solution. A second-order Volterra kernel model was estimated for each of the input-output response pairs. The spectral energy of the responses was also computed, providing a quantitative measure of neuronal excitability. Changes in duration and amplitude of the first-order kernel correlated positively with the spectral energy increase following treatment with low-Mg(2+)/high-K(+) solution, suggesting that variations in neuronal excitability are coded by the system kernels, in part by differences to the profile of the first-order kernel. In particular, kernel duration was more sensitive than amplitude to changes in spectral energy, and correlated more strongly with kernel area. An oscillator network model of the hippocampal CA3 was constructed to investigate the relationship of kernel duration to network excitability, and the model was able to generate spontaneous, recurrent SLEs by increasing the duration of a mode function analogous to the first-order kernel. Results from the model indicated that disruption to the dynamic balance of feedback was responsible for seizure-like transitions and the observed intermittency of SLEs. A physiological candidate for feedback imbalance consistent with the network model is the destabilizing interaction of extracellular potassium and paroxysmal neuronal activation. Altogether, these results (1) validate a mathematical model for

  15. System characterization of neuronal excitability in the hippocampus and its relevance to observed dynamics of spontaneous seizure-like transitions

    NASA Astrophysics Data System (ADS)

    Zalay, Osbert C.; Serletis, Demitre; Carlen, Peter L.; Bardakjian, Berj L.

    2010-06-01

    Most forms of epilepsy are marked by seizure episodes that arise spontaneously. The low-magnesium/high-potassium (low-Mg2+/high-K+) experimental model of epilepsy is an acute model that produces spontaneous, recurring seizure-like events (SLEs). To elucidate the nature of spontaneous seizure transitions and their relationship to neuronal excitability, whole-cell recordings from the intact hippocampus were undertaken in vitro, and the response of hippocampal CA3 neurons to Gaussian white noise injection was obtained before and after treatment with various concentrations of low-Mg2+/high-K+ solution. A second-order Volterra kernel model was estimated for each of the input-output response pairs. The spectral energy of the responses was also computed, providing a quantitative measure of neuronal excitability. Changes in duration and amplitude of the first-order kernel correlated positively with the spectral energy increase following treatment with low-Mg2+/high-K+ solution, suggesting that variations in neuronal excitability are coded by the system kernels, in part by differences to the profile of the first-order kernel. In particular, kernel duration was more sensitive than amplitude to changes in spectral energy, and correlated more strongly with kernel area. An oscillator network model of the hippocampal CA3 was constructed to investigate the relationship of kernel duration to network excitability, and the model was able to generate spontaneous, recurrent SLEs by increasing the duration of a mode function analogous to the first-order kernel. Results from the model indicated that disruption to the dynamic balance of feedback was responsible for seizure-like transitions and the observed intermittency of SLEs. A physiological candidate for feedback imbalance consistent with the network model is the destabilizing interaction of extracellular potassium and paroxysmal neuronal activation. Altogether, these results (1) validate a mathematical model for epileptiform

  16. Lateralization of Temporal Lobe Epilepsy using a Novel Uncertainty Analysis of MR Diffusion in Hippocampus, Cingulum, and Fornix, and Hippocampal Volume and FLAIR Intensity

    PubMed Central

    Nazem-Zadeh, Mohammad-Reza; Schwalb, Jason M.; Elisevich, Kost V.; Bagher-Ebadian, Hassan; Hamidian, Hajar; Akhondi-Asl, Ali-Reza; Jafari-Khouzani, Kourosh; Soltanian-Zadeh, Hamid

    2014-01-01

    Purpose To analyze the utility of a quantitative uncertainty analysis approach for evaluation and comparison of various MRI findings for lateralization of epileptogenicity in mesial temporal lobe epilepsy (mTLE), including novel diffusion-based analyses. Methods We estimated the hemispheric variation uncertainty (HVU) of hippocampal T1 volumetry and FLAIR (Fluid Attenuated Inversion Recovery) intensity. Using diffusion tensor images of 23 nonepileptic subjects, we estimated the HVU levels of mean diffusivity (MD) in the hippocampus, and fractional anisotropy (FA) in the posteroinferior cingulum and crus of fornix. Imaging from a retrospective cohort of 20 TLE patients who had undergone surgical resection with Engel class I outcomes was analyzed to determine whether asymmetry of preoperative volumetrics, FLAIR intensities, and MD values in hippocampi, as well as FA values in posteroinferior cingula and fornix crura correctly predicted laterality of seizure onset. Ten of the cohort had pathologically proven mesial temporal sclerosis (MTS). Seven of these patients had undergone extra-operative electrocorticography (ECoG) for lateralization or to rule out extra-temporal foci. Results HVU was estimated to be 3.1 × 10−5 for hippocampal MD, 0.027 for FA in posteroinferior cingulum, 0.018 for FA in crus of fornix, 0.069 for hippocampal normalized volume, and 0.099 for hippocampal normalized FLAIR intensity. Using HVU analysis, a higher hippocampal MD value, lower FA within the posteroinferior cingulum and crus of fornix, shrinkage in hippocampal volume, and higher hippocampal FLAIR intensity were observed beyond uncertainty on the side ipsilateral to seizure onset for 10, 10, 9, 9, and 10 out of 10 pathology-proven MTS patients, respectively. Considering all 20 TLE patients, these numbers were 18, 15, 14, 13, and 16, respectively. However, consolidating lateralization results of HVU analysis on these quantities by majority voting detected the epileptogenic side for 19

  17. Lateralization of temporal lobe epilepsy using a novel uncertainty analysis of MR diffusion in hippocampus, cingulum, and fornix, and hippocampal volume and FLAIR intensity.

    PubMed

    Nazem-Zadeh, Mohammad-Reza; Schwalb, Jason M; Elisevich, Kost V; Bagher-Ebadian, Hassan; Hamidian, Hajar; Akhondi-Asl, Ali-Reza; Jafari-Khouzani, Kourosh; Soltanian-Zadeh, Hamid

    2014-07-15

    To analyze the utility of a quantitative uncertainty analysis approach for evaluation and comparison of various MRI findings for the lateralization of epileptogenicity in mesial temporal lobe epilepsy (mTLE), including novel diffusion-based analyses. We estimated the hemispheric variation uncertainty (HVU) of hippocampal T1 volumetry and FLAIR (Fluid Attenuated Inversion Recovery) intensity. Using diffusion tensor images of 23 nonepileptic subjects, we estimated the HVU levels of mean diffusivity (MD) in the hippocampus, and fractional anisotropy (FA) in the posteroinferior cingulum and crus of fornix. Imaging from a retrospective cohort of 20 TLE patients who had undergone surgical resection with Engel class I outcomes was analyzed to determine whether asymmetry of preoperative volumetrics, FLAIR intensities, and MD values in hippocampi, as well as FA values in posteroinferior cingula and fornix crura correctly predicted laterality of seizure onset. Ten of the cohort had pathologically proven mesial temporal sclerosis (MTS). Seven of these patients had undergone extraoperative electrocorticography (ECoG) for lateralization or to rule out extra-temporal foci. HVU was estimated to be 3.1×10(-5) for hippocampal MD, 0.027 for FA in posteroinferior cingulum, 0.018 for FA in crus of fornix, 0.069 for hippocampal normalized volume, and 0.099 for hippocampal normalized FLAIR intensity. Using HVU analysis, a higher hippocampal MD value, lower FA within the posteroinferior cingulum and crus of fornix, shrinkage in hippocampal volume, and higher hippocampal FLAIR intensity were observed beyond uncertainty on the side ipsilateral to seizure onset for 10, 10, 9, 9, and 10 out of 10 pathology-proven MTS patients, respectively. Considering all 20 TLE patients, these numbers were 18, 15, 14, 13, and 16, respectively. However, consolidating the lateralization results of HVU analysis on these quantities by majority voting has detected the epileptogenic side for 19 out of 20 cases

  18. Feasibility, safety, and preliminary efficacy of Low Amplitude Seizure Therapy (LAP-ST): A proof of concept clinical trial in man.

    PubMed

    Youssef, Nagy A; Sidhom, Emad

    2017-11-01

    Current pulse amplitude used in clinical ECT may be higher than needed. Reducing pulse amplitude may improve focality of the electric field and thus cognitive adverse effects. Here we examine the feasibility, safety, and whether Low Pulse Amplitude Seizure Therapy (LAP-ST, 0.5-0.6A) minimizes cognitive adverse effects while retaining efficacy. Patients with treatment-resistant primary mood (depressive episodes) or psychotic disorders who were clinically indicated to undergo ECT were offered to be enrolled in an open-label study. The study consisted of a full acute course of LAP-ST under standard anesthesia and muscle relaxation. The primary outcome was feasibility of seizure induction. Clinical outcome measures were: time to reorientation (TRO), Mini Mental State Examination, Montgomery Aberg Depression Scale, and Brief Psychiatric Rating Scale, and Clinical Global Impression Scale. Twenty-two patients consented for enrollment in the study. LAP-ST was feasible, and all patients had seizures in the first session. Participants had a quick orientation with median TRO of 4.5min. Treatment was efficacious for both depressive and psychotic symptoms. Relatively small sample size, non-blinded, and no randomization was performed in this initial proof of concept study. This first human preliminary data of a full course of focal LAP-ST demonstrates that seizure induction is feasible. These results, although preliminary, suggest that the LAP-ST compared to the standard ECT techniques may result in less cognitive side effects, but comparable efficacy. Larger studies are needed to replicate these findings. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Treating acute seizures with benzodiazepines: does seizure duration matter?

    PubMed

    Naylor, David E

    2014-10-01

    Several clinical trials have shown improved seizure control and outcome by early initiation of treatment with benzodiazepines, before arrival in the emergency department and before intravenous access can be established. Here, evidence is provided and reviewed for rapid treatment of acute seizures in order to avoid the development of benzodiazepine pharmacoresistance and the emergence of self-sustaining status epilepticus. Alterations in the physiology, pharmacology, and postsynaptic level of GABA-A receptors can develop within minutes to an hour and hinder the ability of synaptic inhibition to stop seizures while also impairing the efficacy of GABAergic agents, such as benzodiazepines, to boost impaired inhibition. In addition, heightened excitatory transmission further exacerbates the inhibitory/excitatory balance and makes seizure control even more resistant to treatment. The acute increase in the surface expression of NMDA receptors during prolonged seizures also may cause excitotoxic injury, cell death, and other pathological expressions and re-arrangements of receptor subunits that all contribute to long-term sequelae such as cognitive impairment and chronic epilepsy. In conclusion, a short window of opportunity exists when seizures are maximally controlled by first-line benzodiazepine treatment. After that, multiple pathological mechanisms quickly become engaged that make seizures increasingly more difficult to control with high risk for long-term harm.

  20. Is there a predictive value of EEG and MRI after a first afebrile seizure in children?

    PubMed

    Tews, W; Weise, S; Syrbe, S; Hirsch, W; Viehweger, A; Merkenschlager, A; Bertsche, A; Kiess, W; Bernhard, M K

    2015-03-01

    After a first afebrile seizure, EEG in addition to cMRI is recommended for pediatric patients. Once indications requiring immediate treatment are excluded, it is of interest to determine if the results provide a prognostic tool for seizure relapses. Patients aged between 1 month and 18 years who had a first afebrile seizure between 2006 and 2008 were retrospectively studied and monitored for another 48 months. Out of 248 patients, 62.5% had generalized and 36.3% focal seizures. 34.7% of the EEG results were pathological. 176 patients had a cMRI that showed in 23.3% probable epileptogenic lesions. 3 patients with benign cerebral tumours needed surgical therapy. In the following 48 months 29.4% of the children showed seizure relapses. There was a correlation between epileptic patterns in the EEG and further seizures (p=0.0001). However, the sensitivity of the EEG based diagnoses was 0.6, the specificity 0.78 and the positive predictive value 0.52. There was no correlation between epileptogenic lesions and the probability of seizure relapses. The sensitivity of the cMRI to this effect was 0.36, the specificity 0.74 and the positive predictive value 0.34. The EEG is superior to cMRI for predicting seizure relapses. The percentage of noticeable cMRI findings is high but this has low therapeutic relevance and is assumed to largely represent "incidental findings". It is important to question the value of MRI investigations for sedated small children except in the case of emergencies. The key question is whether the cMRI should be deployed to diagnose epilepsy, the probability of seizure recurrences or to classify the entity of a most likely epilepsy. © Georg Thieme Verlag KG Stuttgart · New York.