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Sample records for focal hippocampal seizures

  1. 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. ...

  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 RB, ... 6th ed. Philadelphia, PA: Elsevier Saunders; 2012:chap 67. ...

  3. GABAergic networks jump-start focal seizures.

    PubMed

    de Curtis, Marco; Avoli, Massimo

    2016-05-01

    Abnormally enhanced glutamatergic excitation is commonly believed to mark the onset of a focal seizure. This notion, however, is not supported by firm evidence, and it will be challenged here. A general reduction of unit firing has been indeed observed in association with low-voltage fast activity at the onset of seizures recorded during presurgical intracranial monitoring in patients with focal, drug-resistant epilepsies. Moreover, focal seizures in animal models start with increased γ-aminobutyric acid (GABA)ergic interneuronal activity that silences principal cells. In vitro studies have shown that synchronous activation of GABAA receptors occurs at seizure onset and causes sizeable elevations in extracellular potassium, thus facilitating neuronal recruitment and seizure progression. A paradoxical involvement of GABAergic networks is required for the initiation of focal seizures characterized by low-voltage fast activity, which represents the most common seizure-onset pattern in focal epilepsies. PMID:27061793

  4. Ambroxol-induced focal epileptic seizure.

    PubMed

    Lapenta, Leonardo; Morano, Alessandra; Fattouch, Jinane; Casciato, Sara; Fanella, Martina; Giallonardo, Anna Teresa; Di Bonaventura, Carlo

    2014-01-01

    It is well known that in epileptic patients some compounds and different drugs used for the treatment of comorbidities can facilitate or provoke seizures, this evidence regarding a wide spectrum of pharmacological categories. The potential facilitating factors usually include direct toxic effects or pharmacological interactions of either active ingredients or excipients. We report the case of a patient with drug-resistant epilepsy who experienced focal epileptic seizures, easily and constantly reproducible, after each administration of a cough syrup. This is, to our knowledge, the first electroencephalogram-documented case of focal epileptic seizures induced by cough syrup containing ambroxol as active ingredient. PMID:24824664

  5. 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. PMID:25082395

  6. Focal cooling rapidly terminates experimental neocortical seizures.

    PubMed

    Yang, X F; Rothman, S M

    2001-06-01

    The efficacy of surgical resection for epilepsy is considerably lower for neocortical epilepsy than for temporal lobe epilepsy. We have explored focal cooling with a thermoelectric (Peltier) device as a potential therapy for neocortical epilepsy. After creating a cranial window in anesthetized rats, we induced seizures by injecting artificial cerebrospinal fluid containing 4-aminopyridine (4-AP), a potassium channel blocker. Within 30 minutes of 4-AP injection, animals developed recurrent seizures (duration 85.7 +/- 26.2 seconds; n = 10 rats) that persisted for 2 hours. When a small Peltier device cooled the exposed cortical surface to 20-25 degrees C at seizure onset, the seizure duration was reduced to 8.4 +/- 5.0 seconds (n = 10 rats; p < 0.001). When the Peltier device was placed close to the cortical surface, but not allowed to make physical contact, there was no effect on seizure duration (104.3 +/- 20.7 seconds; p > 0.05 compared to control). Interestingly, the duration of uncooled seizures was reduced after we allowed the cortex to rewarm from prior cooling. Histological examination of the cortex after cooling has shown no evidence of acute or delayed neuronal injury, and blood pressure and temperature remained stable. It may be possible to use Peltier devices for cortical mapping or, when seizure detection algorithms improve, for chronic seizure control. PMID:11409423

  7. 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

  8. Hippocampal internal architecture and postoperative seizure outcome in temporal lobe epilepsy due to hippocampal sclerosis

    PubMed Central

    Elkommos, Samia; Weber, Bernd; Niehusmann, Pitt; Volmering, Elisa; Richardson, Mark P.; Goh, Yen Y.; Marson, Anthony G.; Elger, Christian; Keller, Simon S.

    2016-01-01

    Purpose Semi-quantitative analysis of hippocampal internal architecture (HIA) on MRI has been shown to be a reliable predictor of the side of seizure onset in patients with temporal lobe epilepsy (TLE). In the present study, we investigated the relationship between postoperative seizure outcome and preoperative semi-quantitative measures of HIA. Methods We determined HIA on high in-plane resolution preoperative T2 short tau inversion recovery MR images in 79 patients with presumed unilateral mesial TLE (mTLE) due to hippocampal sclerosis (HS) who underwent amygdalohippocampectomy and postoperative follow up. HIA was investigated with respect to postoperative seizure freedom, neuronal density determined from resected hippocampal specimens, and conventionally acquired hippocampal volume. Results HIA ratings were significantly related to some neuropathological features of the resected hippocampus (e.g. neuronal density of selective CA regions, Wyler grades), and bilaterally with preoperative hippocampal volume. However, there were no significant differences in HIA ratings of the to-be-resected or contralateral hippocampus between patients rendered seizure free (ILAE 1) compared to those continuing to experience seizures (ILAE 2-5). Conclusions This work indicates that semi-quantitative assessment of HIA on high-resolution MRI provides a surrogate marker of underlying histopathology, but cannot prospectively distinguish between patients who will continue to experience postoperative seizures and those who will be rendered seizure free. The predictive power of HIA for postoperative seizure outcome in non-lesional patients with TLE should be explored. PMID:26803053

  9. Patient considerations in the management of focal seizures in children and adolescents

    PubMed Central

    Kenney, Daniel; Wirrell, Elaine

    2014-01-01

    Focal epilepsy accounts for approximately one-half to two-thirds of new-onset epilepsy in children. Etiologies are diverse, and range from benign epilepsy syndromes with normal neuroimaging and almost certain remission to focal malformations of cortical development or hippocampal sclerosis with intractable seizures persisting lifelong. Other important etiologies in children include pre-, peri-, or postnatal brain injury, low-grade neoplasms, vascular lesions, and neuroimmunological disorders. Cognitive, behavioral, and psychiatric comorbidities are commonly seen and must be addressed in addition to seizure control. Given the diverse nature of focal epilepsies in children and adolescents, investigations and treatments must be individualized. First-line therapy consists of prophylactic antiepileptic drugs; however, prognosis is poor after failure of two to three drugs for lack of efficacy. Refractory cases should be referred for an epilepsy surgery workup. Dietary treatments and neurostimulation may be considered in refractory cases who are not good candidates for surgery. PMID:24808722

  10. 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

  11. 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

  12. Microscale spatiotemporal dynamics during neocortical propagation of human focal seizures.

    PubMed

    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

    2015-11-15

    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 multiunit 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, ~2-3 Hz) 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 MUA

  13. Coexistent ganglioglioma, focal cortical dysplasia, and hippocampal sclerosis (triple pathology) in chronic epilepsy.

    PubMed

    Prayson, Richard A; Gales, Jordan M

    2015-10-01

    The most commonly identified pathologies in patients with medically intractable epilepsy include focal cortical dysplasia, hippocampal sclerosis, tumors, and remote ischemic damage. Surgery has proven to be an effective therapeutic modality in most of such patients. The coexistence of multiple pathologies in resected tissues is well documented, particularly ganglioglioma and focal cortical dysplasia. Cases of triple pathology are, however, extraordinarily unusual. We report 2 cases of triple pathology including hippocampal sclerosis, ganglioglioma, and focal cortical dysplasia. Cases of pathologically confirmed hippocampal sclerosis diagnosed between January 2000 to December 2012 (n= 349) were reviewed, and only 2 cases (0.6%) with triple pathology were identified. The histopathologic and clinical features of these 2 cases are reviewed. The patients included a 6-year-old girl and 10-year-old boy. The former patient presented with a 4-year history of epilepsy and oppositional defiant disorder. Imaging identified a lesion in the left parahippocampal gyrus and posterior hippocampus. The latter patient presented with an 8-year history of epilepsy, attention deficient hyperactivity disease, and a pervasive developmental disorder. Imaging identified a lesion in the left posterior temporal and occipital region. Resected tissues in both patients showed a ganglioglioma (World Health Organization grade I) with accompanying focal cortical dysplasia and hippocampal sclerosis. Both patients were seizure free on antiepileptic medication at last follow-up at 20 and 38 months, respectively. The prevalence of triple pathology including hippocampal sclerosis is low (<1% in the current study). Surgical intervention for triple pathology cases anecdotally appears effective in achieving seizure control. PMID:26235882

  14. [FOCAL MOTOR SEIZURES AND STATUS EPILEPTICUS PROVOKED BY MIRTAZAPINE].

    PubMed

    Dömötör, Johanna; Clemens, Béla

    2015-07-30

    The seizure-provoking effect of the tetracyclic antidepressant mirtazapine is not a well-known adverse effect of the drug. The authors report on a 39-year-old non-epileptic patient who had been treated for depression with the usual daily dose of mirtazapine. Having increased the daily dose of the drug from 30 to 45 milligrams he experienced a few clonic seizures of the right lower limb. This symptom and insomnia erroneously intended the patient to further increase the daily dose of mirtazapine, which immediately resulted in the evolution of focal clonic status epilepticus in the same limb. After admission, this condition was recorded by video-EEG and abolished by intravenous administration of levetiracetam after the intravenous clonazepam had been ineffective. Discontinuation of mirtazapine and administration of carbamazepine resulted in completely seizure-free state that persisted even after carbamazepine treatment was terminated. The clinical and laboratory data indicate the seizure-provoking effect of mirtazapine in the reported case. PMID:26380424

  15. Ictal electrographic pattern of focal subcortical seizures induced by sound in rats.

    PubMed

    Vinogradova, Lyudmila V; Grinenko, Olesya A

    2016-03-15

    It is now recognized that both generalized and focal seizures may originate in subcortical structures. The well-known types of focal subcortically-driven seizures are gelastic seizures in patients with the hypothalamic hamartoma and sound-induced seizures in rodents with audiogenic epilepsy. The seizures are generated by subcortical intrinsically epileptogenic focus, the hamartoma in humans and the inferior colliculus (IC) in rodents. In patients with gelastic epilepsy additional seizure types may develop with time that are supposed to result from secondary epileptogenesis and spreading of epileptic discharges to the cortex. Repeated audiogenic seizures can also lead to development of additional seizure behavior and secondary epileptic activation of the cortex. This process, named audiogenic kindling, may be useful for studying secondary subcortico-cortical epileptogenesis. Using intracollicular and intracortical recordings, we studied an ictal electrographic pattern of focal subcortical seizures induced by repeated sound stimulation in Wistar audiogenic-susceptible rats. The audiogenic seizures, representing brief attacks of paroxysmal unidirectional running, were accompanied by epileptiform abnormalities in the IC, mostly on the side ipsilateral to run direction, and enhanced rhythmic 8-9Hz activity in the cortex. With repetition of the subcortical seizures and kindling development, a secondary cortical discharge began to follow the IC seizure. The secondary discharge initially involved the cortex homolateral to the side of dominant subcortical epileptiform abnormalities and behaviorally expressed as limbic (partial) clonus. Kindling progression was associated with bilateralization of the secondary cortical discharge, an increase in its amplitude and duration, intensification of associated behavioral seizures (from partial clonus to generalized tonic-clonic convulsions). Thus, ictal recordings during brief audiogenic running seizures showed their focal

  16. 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

  17. Convulsive seizures from experimental focal cortical dysplasia occur independently of cell misplacement

    PubMed Central

    Hsieh, Lawrence S.; Wen, John H.; Claycomb, Kumiko; Huang, Yuegao; Harrsch, Felicia A.; Naegele, Janice R.; Hyder, Fahmeed; Buchanan, Gordon F.; Bordey, Angelique

    2016-01-01

    Focal cortical dysplasia (FCD), a local malformation of cortical development, is the most common cause of pharmacoresistant epilepsy associated with life-long neurocognitive impairments. It remains unclear whether neuronal misplacement is required for seizure activity. Here we show that dyslamination and white matter heterotopia are not necessary for seizure generation in a murine model of type II FCDs. These experimental FCDs generated by increasing mTOR activity in layer 2/3 neurons of the medial prefrontal cortex are associated with tonic-clonic seizures and a normal survival rate. Preventing all FCD-related defects, including neuronal misplacement and dysmorphogenesis, with rapamycin treatments from birth eliminates seizures, but seizures recur after rapamycin withdrawal. In addition, bypassing neuronal misplacement and heterotopia using inducible vectors do not prevent seizure occurrence. Collectively, data obtained using our new experimental FCD-associated epilepsy suggest that life-long treatment to reduce neuronal dysmorphogenesis is required to suppress seizures in individuals with FCD. PMID:27249187

  18. SEIZURES IN EARLY-LIFE SUPPRESS HIPPOCAMPAL DENDRITE GROWTH WHILE IMPAIRING SPATIAL LEARNING

    PubMed Central

    Nishimura, Masataka; Gu, Xue; Swann, John W.

    2011-01-01

    Impaired learning and memory are common in epilepsy syndromes of childhood. Clinical investigations suggest that the developing brain may be particularly vulnerable to the effects of intractable seizure disorders. Magnetic resonance imaging (MRI) studies have demonstrated reduced volumes in brain regions involved in learning and memory. The earlier the onset of an epilepsy the larger the effects seem to be on both brain anatomy and cognition. Thus, childhood epilepsy has been proposed to interfere in some unknown way with brain development. Experiments reported here explore these ideas by examining the effects of seizures in infant mice on learning and memory and on the growth of CA1 hippocampal pyramidal cell dendrites. Fifteen brief seizures were induced by flurothyl between postnatal days 7 and 11 in mice that express green fluorescent protein (GFP) in hippocampal pyramidal cells. One to 44 days later, dendritic arbors were reconstructed to measure growth. Spatial learning and memory were also assessed in a water maze. Our results show that recurrent seizures produced marked deficits in learning and memory. Seizures also dramatically slowed the growth of basilar dendrites while neurons in litter-mate control mice continued to add new dendritic branches and lengthen existing branches. When experiments were performed in older mice, seizures had no measureable effects on either dendrite arbor complexity or spatial learning and memory. Our results suggest that the recurring seizures of intractable childhood epilepsy contribute to associated learning and memory deficits by suppressing dendrite growth. PMID:21777677

  19. 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

  20. 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. PMID:22692938

  1. 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

  2. A rule-based seizure prediction method for focal neocortical epilepsy

    PubMed Central

    Aarabi, Ardalan; He, Bin

    2012-01-01

    Objective In the present study, we have developed a novel patient-specific rule-based seizure prediction system for focal neocortical epilepsy. Methods Five univariate measures including correlation dimension, correlation entropy, noise level, Lempel-Ziv complexity, and largest Lyapunov exponent as well as one bivariate measure, nonlinear interdependence, were extracted from non-overlapping 10-second segments of intracranial electroencephalogram (iEEG) data recorded using electrodes implanted deep in the brain and/or placed on the cortical surface. The spatio-temporal information was then integrated by using rules established based on patient-specific changes observed in the period prior to a seizure sample for each patient. The system was tested on 316 h of iEEG data containing 49 seizures recorded in eleven patients with medically intractable focal neocortical epilepsy. Results For seizure occurrence periods of 30 and 50 min our method showed an average sensitivity of 79.9% and 90.2% with an average false prediction rate of 0.17 and 0.11/h, respectively. In terms of sensitivity and false prediction rate, the system showed superiority to random and periodical predictors. Conclusions The nonlinear analysis of iEEG in the period prior to seizures revealed patient-specific spatio-temporal changes that were significantly different from those observed within baselines in the majority of the seizures analyzed in this study. Significance The present results suggest that the patient specific rule-based approach may become a potentially useful approach for predicting seizures prior to onset. PMID:22361267

  3. Isovaline attenuates generalized epileptiform activity in hippocampal and primary sensory cortices and seizure behavior in pilocarpine treated rats.

    PubMed

    Yu, Wilson; Smith, Autumn B; Pilitsis, Julie G; Shin, Damian S

    2015-07-10

    Anti-seizure drugs are the most commonly employed treatment option for epilepsy and these generally provide effective management of seizures. However, 30% of patients with epilepsy are not adequately treated with anti-seizure medications and are considered intractable. Recently we reported that isovaline, a unique amino acid, could attenuate seizure like events (SLEs) in two in vitro hippocampal seizure models by selectively increasing the activity of interneurons, but not pyramidal neurons. Isovaline also attenuated hippocampal epileptiform activity and behavioral seizures in vivo in rats administered 4 aminopyridine (4AP). Here, we investigate whether isovaline is efficacious in attenuating secondarily generalized epileptiform activity and behavioral seizures in rats administered pilocarpine. We found that 150 mg/kg isovaline administered intravenously abolished pilocarpine-induced epileptiform activity in the primary sensory cortex and hippocampus and attenuated generalized forebrain behavioral seizures. We are the first to demonstrate that isovaline may be a plausible anti-seizure drug for secondarily generalized seizures and this could potentially lead to the development of a novel class of anti-seizure drugs focused around the unique mechanism(s) of isovaline. PMID:26007701

  4. Diabetic hyperglycemia aggravates seizures and status epilepticus-induced hippocampal damage.

    PubMed

    Huang, Chin-Wei; Cheng, Juei-Tang; Tsai, Jing-Jane; Wu, Sheng-Nan; Huang, Chao-Ching

    2009-01-01

    Epileptic seizures in diabetic hyperglycemia (DH) are not uncommon. This study aimed to determine the acute behavioral, pathological, and electrophysiological effects of status epilepticus (SE) on diabetic animals. Adult male Sprague-Dawley rats were first divided into groups with and without streptozotocin (STZ)-induced diabetes, and then into treatment groups given a normal saline (NS) (STZ-only and NS-only) or a lithium-pilocarpine injection to induce status epilepticus (STZ + SE and NS + SE). Seizure susceptibility, severity, and mortality were evaluated. Serial Morris water maze test and hippocampal histopathology results were examined before and 24 h after SE. Tetanic stimulation-induced long-term potentiation (LTP) in a hippocampal slice was recorded in a multi-electrode dish system. We also used a simulation model to evaluate intracellular adenosine triphosphate (ATP) and neuroexcitability. The STZ + SE group had a significantly higher percentage of severe seizures and SE-related death and worse learning and memory performances than the other three groups 24 h after SE. The STZ + SE group, and then the NS + SE group, showed the most severe neuronal loss and mossy fiber sprouting in the hippocampal CA3 area. In addition, LTP was markedly attenuated in the STZ + SE group, and then the NS + SE group. In the simulation, increased intracellular ATP concentration promoted action potential firing. This finding that rats with DH had more brain damage after SE than rats without diabetes suggests the importance of intensively treating hyperglycemia and seizures in diabetic patients with epilepsy. PMID:19384590

  5. Hyperintense cortical signal on MRI reflects focal leukocortical encephalitis and seizure risk in PML

    PubMed Central

    Khoury, Michael N.; Alsop, David C.; Agnihotri, Shruti P.; Pfannl, Rolf; Wuthrich, Christian; Ho, Mai-Lan; Hackney, David; Ngo, Long; Anderson, Matthew P.; Koralnik, Igor J.

    2015-01-01

    Objective To determine the frequency of hyperintense cortical signal (HCS) on T1-weighted pre-contrast MRI in progressive multifocal leukoencephalopathy (PML) patients, its association with seizure risk and immune reconstitution inflammatory syndrome (IRIS), and its pathologic correlate. Methods We reviewed clinical data including seizure history, presence of IRIS, and MRI scans from PML patients evaluated at our institution between 2003 and 2012. Cases that were diagnosed either by CSF JC Virus (JCV) PCR, brain biopsy or autopsy, and who had MRI images available were included in the analysis (n=49). We characterized pathologic findings in areas of the brain displaying HCS in two patients and compared them with isointense cortex in the same individuals. Results Of 49 patients, 17 (34.7%) had seizures and 30 (61.2%) had HCS adjacent to subcortical PML lesions on MRI. Of the 17 PML patients with seizures, 15 (88.2%) had HCS compared to 15/32 (46.9%) patients without seizures (p= 0.006). HCS was associated with seizure development with a relative risk (RR) of 4.75 (95% confidence interval of 1.2 to 18.5; p=0.006). Of the 20 patients with IRIS, 16 (80.0%) had HCS compared to 14/29 (49.3%) of those without IRIS (p=0.04). On histological examination, HCS areas were associated with striking JCV-associated demyelination of cortical and sub-cortical U-fibers, significant macrophage infiltration and a pronounced reactive gliosis in the deep cortical layers. Interpretation Seizures are a frequent complication in PML. HCS is associated with seizures as well as IRIS, and correlates histologically with JCV focal leukocortical encephalitis (JCV FLE). PMID:24752885

  6. Focal seizures and epileptic spasms in a child with Down syndrome from a family with a PRRT2 mutation.

    PubMed

    Igarashi, Ayuko; Okumura, Akihisa; Shimojima, Keiko; Abe, Shinpei; Ikeno, Mitsuru; Shimizu, Toshiaki; Yamamoto, Toshiyuki

    2016-06-01

    We describe a girl with Down syndrome who experienced focal seizures and epileptic spasms during infancy. The patient was diagnosed as having trisomy 21 during the neonatal period. She had focal seizures at five months of age, which were controlled with phenobarbital. However, epileptic spasms appeared at seven months of age in association with hypsarrhythmia. Upon treatment with adrenocorticotropic hormone, her epileptic spasms disappeared. Her younger brother also had focal seizures at five months of age. His development and interictal electroencephalogram were normal. The patient's father had had infantile epilepsy and paroxysmal kinesigenic dyskinesia. We performed a mutation analysis of the PRRT2 gene and found a c.841T>C mutation in the present patient, her father, and in her younger brother. We hypothesized that the focal seizures in our patient were caused by the PRRT2 mutation, whereas the epileptic spasms were attributable to trisomy 21. PMID:26867511

  7. Focal inhibitory seizure with prolonged deficit in adult Sturge-Weber syndrome.

    PubMed

    Aupy, Jerome; Bonnet, Charlotte; Arnould, Jean-Simon; Fernandez, Philippe; Marchal, Cecile; Zanotti-Fregonara, Paolo

    2015-09-01

    Sturge-Weber syndrome is a sporadic congenital neurocutaneous disorder often related to varying degrees of motor impairment. The phenomenon of prolonged ictal paresis is a rare seizure sign that can be due to lesions affecting the centro-parietal lobe. Focal inhibitory motor seizures can be difficult to differentiate from other clinical entities such as stroke, migraine or postictal paresis. We describe the case of a 40-year-old patient suffering from Sturge-Weber syndrome, admitted due to prolonged right-sided hemiparesis following a usual seizure. Repeated EEGs during the prolonged deficit showed only intermittent left fronto-parietal sharp waves. (99m)Tc HMPAO-brain SPECT performed seven days after the last seizure showed a vast area of parieto-occipital hyperperfusion in the left hemisphere. Aggressive antiepileptic therapy dramatically improved the clinical symptoms and scintigraphic images, which corroborated the diagnosis of ictal paresis. This case highlights the role of SPECT in the evaluation of Sturge-Weber syndrome, not only to investigate progressive neurological deterioration, but also exacerbation of seizures or prolonged neurological deficits. In fact, it may be possible to document ongoing epileptic activity using SPECT, despite a non-contributory EEG, which may be of help in adapting a therapeutic strategy. PMID:26235101

  8. Seizures

    MedlinePlus

    ... minutes The person does not awaken or have normal behavior after a seizure Another seizure starts soon after a seizure ends The person had a seizure in water The person is pregnant, injured, or has diabetes ...

  9. Seizures

    MedlinePlus

    ... two or more seizures may be diagnosed with epilepsy , also known as seizure disorder. Seizure Basics Under ... over and over might indicate the ongoing condition epilepsy . Febrile seizures can happen in children younger than ...

  10. Seizures

    MedlinePlus

    ... Story" 5 Things to Know About Zika & Pregnancy First Aid: Seizures KidsHealth > For Parents > First Aid: Seizures Print A A A Text Size en ... Seizures Febrile Seizures Brain and Nervous System Epilepsy First Aid: Febrile Seizures Word! Seizure Epilepsy Epilepsy Contact Us ...

  11. A novel STXBP1 mutation causes focal seizures with neonatal onset.

    PubMed

    Vatta, Matteo; Tennison, Michael B; Aylsworth, Arthur S; Turcott, Christie M; Guerra, Maria P; Eng, Christine M; Yang, Yaping

    2012-06-01

    Mutations of the syntaxin binding protein 1 (STXBP1) have been associated with severe infantile epileptic encephalopathies (Ohtahara syndrome and West syndrome), but also with moderate to severe cognitive impairment and nonsyndromic epilepsy. We have studied a white infant who presented with focal seizures at age 2 weeks. Brain imaging was unremarkable. The electroencephalograph (EEG) demonstrated normal background frequency content but with multifocal sharp waves and no evidence of the typical patterns associated with Ohtahara or West syndrome. Therapy with levetiracetam and oxcarbazepine effectively managed the seizure episodes. Investigation of genes associated with infantile forms of epilepsy such as SCN1A, SCN1B, and ARX were negative, but we identified a novel single-nucleotide duplication mutation, c.931dupT (p.S311FfsX3), in exon 11 of the STXBP1 gene. This previously unreported STXBP1 mutation in a subject with neonatal-onset focal seizures broadens the spectrum of clinically relevant human disorders caused by STXBP1 mutations. PMID:22596016

  12. The Role of Gastrodin on Hippocampal Neurons after N-Methyl-D-Aspartate Excitotoxicity and Experimental Temporal Lobe Seizures.

    PubMed

    Wong, Shi-Bing; Hung, Wei-Chen; Min, Ming-Yuan

    2016-06-30

    Tian ma (Gastrodia elata, GE) is an ancient Chinese herbal medicine that has been suggested to be effective as an anticonvulsant and analgesic, and to have sedative effects against vertigo, general paralysis, epilepsy and tetanus. The primary active ingredient isolated from GE is termed gastrodin, which is the glucoside of 4-hydroxybenzyl alcohol (4-HBA). Gastrodin can abolish hypoxia-, glutamate- and N-methyl-D-aspartate (NMDA) receptor-induced toxicity in primary culture of rat cortical neurons, and reduces seizure severity in seizure-sensitive gerbils. We evaluated the effect of gastrodin on NMDA excitotoxicity in hippocampal slice cultures (HSCs) with propidium iodide (PI) fluorescence measurement. We also evaluated the effects of gastrodin for treating active in vivo temporal lobe seizures induced by lithium/pilocarpine. Seizure severity, time span to seizure onset, mortality rate and hippocampal histology for survivors were compared. The effect of gastrodin was evaluated for treating in vitro seizures induced by Mg²⁺-free medium in hippocampal slices. Frequencies and amplitudes of epileptiform discharges were compared. The effect of gastrodin on synaptic transmission was evaluated on hippocampal CA1 Schaffer collaterals. Application of 25 μM gastrodin significantly suppressed NMDA excitotoxicity in CA3 but not in CA1 hippocampus and dentate gyrus. Intraventricular gastrodin accelerated seizure onset for 12 min after intraperitoneal pilocarpine injection (P = 0.051). Three of five rats (60%) in the gastrodin group, and three of four (75%) in the dimethyl sulfoxide (DMSO) group died within 3 days after status epilepticus (SE). Gastrodin also failed to inhibit epileptiform discharges in hippocampal slices induced by Mg²⁺-free medium, believed to be NMDA receptor-mediated spontaneous activity. The frequencies of the spontaneous epileptiform discharges were similar under treatments with 25 μM gastrodin, 200 μM gastrodin and DMSO. For the evaluation of

  13. 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.

  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. PMID:22772373

  15. Chronic Trigeminal Nerve Stimulation Protects Against Seizures, Cognitive Impairments, Hippocampal Apoptosis, and Inflammatory Responses in Epileptic Rats.

    PubMed

    Wang, Qian-Qian; Zhu, Li-Jun; Wang, Xian-Hong; Zuo, Jian; He, Hui-Yan; Tian, Miao-Miao; Wang, Lei; Liang, Gui-Ling; Wang, Yu

    2016-05-01

    Trigeminal nerve stimulation (TNS) has recently been demonstrated effective in the treatment of epilepsy and mood disorders. Here, we aim to determine the effects of TNS on epileptogenesis, cognitive function, and the associated hippocampal apoptosis and inflammatory responses. Rats were injected with pilocarpine to produce status epilepticus (SE) and the following chronic epilepsy. After SE induction, TNS treatment was conducted for 4 consecutive weeks. A pilocarpine re-injection was then used to induce a seizure in the epileptic rats. The hippocampal neuronal apoptosis induced by seizure was assessed by TUNEL staining and inflammatory responses by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). The spontaneous recurrent seizure (SRS) number was counted through video monitoring, and the cognitive function assessed through Morris Water Maze (MWM) test. TNS treatment attenuated the SRS attacks and improved the cognitive impairment in epileptic rats. A pilocarpine re-injection resulted in less hippocampal neuronal apoptosis and reduced level of interleukin-1 beta (IL-1β), tumor necrosis factor-α (TNF-α), and microglial activation in epileptic rats with TNS treatment in comparison to the epileptic rats without TNS treatment. It is concluded that TNS treatment shortly after SE not only protected against the chronic spontaneous seizures but also improved cognitive impairments. These antiepileptic properties of TNS may be related to its attenuating effects on hippocampal apoptosis and pro-inflammatory responses. PMID:26973056

  16. 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 PMID:26854742

  17. Accumulation of abnormal adult-generated hippocampal granule cells predicts seizure frequency and severity

    PubMed Central

    Hester, Michael S.; Danzer, Steve C.

    2013-01-01

    Accumulation of abnormally integrated, adult-born, hippocampal dentate granule cells (DGC) is hypothesized to contribute to the development of temporal lobe epilepsy (TLE). DGCs have long been implicated in TLE, as they regulate excitatory signaling through the hippocampus and exhibit neuroplastic changes during epileptogenesis. Furthermore, DGCs are unusual in that they are continually generated throughout life, with aberrant integration of new cells underlying the majority of restructuring in the dentate during epileptogenesis. While it is known that these abnormal networks promote abnormal neuronal firing and hyperexcitability, it has yet to be established whether they directly contribute to seizure generation. If abnormal DGCs do contribute, a reasonable prediction would be that the severity of epilepsy will be correlated with the number or load of abnormal DGCs. To test this prediction, we utilized a conditional, inducible transgenic mouse model to fate-map adult-generated DGCs. Mossy cell loss, also implicated in epileptogenesis, was assessed as well. Transgenic mice rendered epileptic using the pilocarpine-status epilepticus model of epilepsy were monitored 24/7 by video/EEG for four weeks to determine seizure frequency and severity. Positive correlations were found between seizure frequency and: 1) the percentage of hilar ectopic DGCs, 2) the amount of mossy fiber sprouting and 3) the extent of mossy cell death. In addition, mossy fiber sprouting and mossy cell death were correlated with seizure severity. These studies provide correlative evidence in support of the hypothesis that abnormal DGCs contribute to the development of TLE, and also support a role for mossy cell loss. PMID:23699504

  18. N-methyl-D-aspartate and non-N-methyl-D-aspartate receptors mediate seizures and CA1 hippocampal damage induced by dendrotoxin-K in rats.

    PubMed

    Bagetta, G; Iannone, M; Palma, E; Nisticò, G; Dolly, J O

    1996-04-01

    The epileptogenic and neurodegenerative effects of dendrotoxin K, from Dendroaspis polylepis, a specific blocker of a non-inactivating, voltage-sensitive K+ channel, were studied after focal injection into one dorsal hippocampus in rats. Administration of 35 pmol dendrotoxin K elicited motor seizures and bilateral electrocortical discharges after a latent period (5.3 +/- 2.1 min), in all of the treated animals (n = 6). At 24 h, histological examination of brain (n = 5) coronal sections (10 microns; n = 6 per brain) detected bilateral damage to the hippocampal formation which extended 300 microns rostral and caudal to the injection tract. Quantitation of the damage revealed significant bilateral neuronal cell loss in the CA1 and CA4 pyramidal cell layer relative to the corresponding brain regions of rats (n = 3) injected with bovine serum albumin (105 pmol), which per se was ineffective in all respects. Dendrotoxin K (35 pmol) also caused a significant loss of CA3 pyramidal neurons and dentate gyrus granule cells ipsilateral to the site of toxin injection. In one out of six rats, a lower dose (3.5 pmol) of dendrotoxin K produced convulsive behaviour and electrocortical seizures but after a longer latency and these were accompanied by significant neuronal loss in the CA1, CA3 and CA4 pyramidal cell layer ipsilateral to the injected side. The lowest dose (0.35 pmol; n = 6 rats) of dendrotoxin K used failed to induce seizures and did not cause hippocampal damage (n = 6 rats). Systemic (i.p.) treatment with dizocilpine maleate (3 mg/kg) or LY 274614 (5 mg/kg i.p.), two N-methyl-D-aspartate receptor antagonists (given 15 min beforehand), prevented dendrotoxin K (35 pmol)-induced motor seizures and electrocortical epileptogenic discharges in 100% of the animals (n = 6 per group) treated. Similarly, these antagonists minimized the damage typically produced in the rat hippocampus, with no significant neuronal loss being observed. By contrast, NBQX (30 mg/kg, i.p. given 15

  19. Effects of genistein on cognitive dysfunction and hippocampal synaptic plasticity impairment in an ovariectomized rat kainic acid model of seizure.

    PubMed

    Khodamoradi, Mehdi; Asadi-Shekaari, Majid; Esmaeili-Mahani, Saeed; Esmaeilpour, Khadije; Sheibani, Vahid

    2016-09-01

    The major objective of this study was to investigate the probable effects of genistein (one of the most important soy phytoestrogens-SPEs) on seizure-induced cognitive dysfunction, hippocampal early long-term potentiation (E-LTP) impairment and morphological damage to CA1 neurons in ovariectomized (OVX) rats. Three weeks after ovariectomy, cannulae were implanted over the left lateral ventricle. After a 7-day recovery period, animals were injected by genistein (0.5 or 5mg/kg) or vehicle during four consecutive days, each 24h. One h after the last treatment, kainic acid (KA) or vehicle was perfused into the left lateral ventricle to induce generalized tonic-clonic seizures. Finally, 7 days later, spatial learning and memory of animals were examined using the Morris water maze (MWM) task, hippocampal E-LTP was assessed using in-vivo field potential recordings and the morphology of hippocampal CA1 area was examined using Fluoro-Jade C staining. KA-induced generalized seizures resulted in spatial learning and memory impairment, E-LTP deficit and CA1 cell injury. Seizure-induced abnormalities improved partially only by the lower dose of genistein (0.5mg/kg). However, genistein at the higher dose (5mg/kg) did not have any beneficial effects. Also, genistein did not affect seizure activity. It is concluded that genistein may have partially preventive effects against seizure-induced cognitive impairment in OVX rats. Also, it seems that such effects of genistein are correlated with its beneficial effects on hippocampal synaptic plasticity and morphology. PMID:27235295

  20. A guinea pig hippocampal slice model of organophosphate-induced seizure activity.

    PubMed

    Harrison, Patrick K; Sheridan, Robert D; Green, A Chris; Scott, Iain R; Tattersall, John E H

    2004-08-01

    Extracellular recording techniques have been used in the guinea pig hippocampal slice preparation to investigate the electrophysiological actions of the organophosphate (OP) anticholinesterase soman. When applied at a concentration of 100 nM, soman induced epileptiform activity in the CA1 region in approximately 75% of slices. This effect was mimicked by the anticholinesterases paraoxon (1 and 3 microM), physostigmine (30 microM), and neostigmine (30 microM), thus providing indirect evidence that the epileptiform response was mediated by elevated acetylcholine levels. Soman-induced bursting was inhibited by the muscarinic receptor antagonists atropine (concentrations tested, 0.1-10 microM), telenzepine (0.03-3 microM), AF-DX116 [11-(2-[(diethylamino)methyl]-1-piperidinyl acetyl)-5,11-dihydro-6H-pyrido 92.b-b) (1,4)-benzodiazepin-6-one] (0.3-300 microM), and biperiden (0.1-10 microM) and by the benzodiazepine anticonvulsants diazepam (3-30 microM) and midazolam (3-30 microM), but it was not inhibited by the nicotinic antagonists mecamylamine (30 microM) and methyllycaconitine (300 nM). In contrast to soman-induced epileptiform activity, bursting induced by the K(+) channel blocker 4-aminopyridine (30 microM), the adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (30 nM) or perfusion with low Mg(2+) buffer was insensitive to atropine (10 microM). The ability of muscarinic antagonists and benzodiazepines to inhibit soman-induced epileptiform activity is in accordance with the in vivo pharmacology of soman-induced seizures and suggests that the guinea pig hippocampal slice preparation may provide a useful tool for the evaluation of novel anticonvulsant therapies for the treatment of seizures related to OP poisoning. PMID:15031302

  1. [Seizure].

    PubMed

    Saito, Ayumi; Terayama, Yasuo

    2013-06-01

    Seizure is defined as "a strong shrinkage state of the skeletal muscle which is involuntary, and occurs spasmodically" and it is often accompanied by disturbance of consciousness. The typical disease which causes seizure is epilepsy. But there is many conditions causing seizure. Therefore, diagnosis of epilepsy should be careful. Seizure among eldery increases in an era of an aging population in Japan. The risk of recurrence of seizure or epilepsy in elderly is higher than that in youth. In considering of the treatment of seizure among elderly, differential diagnosis from various condition must be done. PMID:23855204

  2. Nearly Automatic Segmentation of Hippocampal Subfields in In Vivo Focal T2-Weighted MRI

    PubMed Central

    Yushkevich, Paul A.; Wang, Hongzhi; Pluta, John; Das, Sandhitsu R.; Craige, Caryne; Avants, Brian B.; Weiner, Michael W.; Mueller, Susanne

    2010-01-01

    We present and evaluate a new method for automatically labeling the subfields of the hippocampal formation in focal 0.4×0.5×2.0mm3 resolution T2-weighted magnetic resonance images that can be acquired in the routine clinical setting with under 5 min scan time. The method combines multi-atlas segmentation, similarity-weighted voting, and a novel learning-based bias correction technique to achieve excellent agreement with manual segmentation. Initial partitioning of MRI slices into hippocampal ‘head’, ‘body’ and ‘tail’ slices is the only input required from the user, necessitated by the nature of the underlying segmentation protocol. Dice overlap between manual and automatic segmentation is above 0.87 for the larger subfields, CA1 and dentate gyrus, and is competitive with the best results for whole-hippocampus segmentation in the literature. Intraclass correlation of volume measurements in CA1 and dentate gyrus is above 0.89. Overlap in smaller hippocampal subfields is lower in magnitude (0.54 for CA2, 0.62 for CA3, 0.77 for subiculum and 0.79 for entorhinal cortex) but comparable to overlap between manual segmentations by trained human raters. These results support the feasibility of subfield-specific hippocampal morphometry in clinical studies of memory and neurodegenerative disease. PMID:20600984

  3. Seizures

    MedlinePlus

    ... defects) Brain tumor (rare) Drug abuse Electric shock Epilepsy Fever (particularly in young children) Head injury Heart ... age. There may be a family history of epilepsy or seizures. If seizures continue repeatedly after the ...

  4. Mutations in SLC12A5 in epilepsy of infancy with migrating focal seizures.

    PubMed

    Stödberg, Tommy; McTague, Amy; Ruiz, Arnaud J; Hirata, Hiromi; Zhen, Juan; Long, Philip; Farabella, Irene; Meyer, Esther; Kawahara, Atsuo; Vassallo, Grace; Stivaros, Stavros M; Bjursell, Magnus K; Stranneheim, Henrik; Tigerschiöld, Stephanie; Persson, Bengt; Bangash, Iftikhar; Das, Krishna; Hughes, Deborah; Lesko, Nicole; Lundeberg, Joakim; Scott, Rod C; Poduri, Annapurna; Scheffer, Ingrid E; Smith, Holly; Gissen, Paul; Schorge, Stephanie; Reith, Maarten E A; Topf, Maya; Kullmann, Dimitri M; Harvey, Robert J; Wedell, Anna; Kurian, Manju A

    2015-01-01

    The potassium-chloride co-transporter KCC2, encoded by SLC12A5, plays a fundamental role in fast synaptic inhibition by maintaining a hyperpolarizing gradient for chloride ions. KCC2 dysfunction has been implicated in human epilepsy, but to date, no monogenic KCC2-related epilepsy disorders have been described. Here we show recessive loss-of-function SLC12A5 mutations in patients with a severe infantile-onset pharmacoresistant epilepsy syndrome, epilepsy of infancy with migrating focal seizures (EIMFS). Decreased KCC2 surface expression, reduced protein glycosylation and impaired chloride extrusion contribute to loss of KCC2 activity, thereby impairing normal synaptic inhibition and promoting neuronal excitability in this early-onset epileptic encephalopathy. PMID:26333769

  5. The algorithmic complexity of neural spike trains increases during focal seizures.

    PubMed

    Rapp, P E; Zimmerman, I D; Vining, E P; Cohen, N; Albano, A M; Jiménez-Montaño, M A

    1994-08-01

    The interspike interval spike trains of spontaneously active cortical neurons can display nonrandom internal structure. The degree of nonrandom structure can be quantified and was found to decrease during focal epileptic seizures. Greater statistical discrimination between the two physiological conditions (normal vs seizure) was obtained with measurements of context-free grammar complexity than by measures of the distribution of the interspike intervals such as the mean interval, its standard deviation, skewness, or kurtosis. An examination of fixed epoch data sets showed that two factors contribute to the complexity: the firing rate and the internal structure of the spike train. However, calculations with randomly shuffled surrogates of the original data sets showed that the complexity is not completely determined by the firing rate. The sequence-sensitive structure of the spike train is a significant contributor. By combining complexity measurements with statistically related surrogate data sets, it is possible to classify neurons according to the dynamical structure of their spike trains. This classification could not have been made on the basis of conventional distribution-determined measures. Computations with more sophisticated kinds of surrogate data show that the structure observed using complexity measures cannot be attributed to linearly correlated noise or to linearly correlated noise transformed by a static monotonic nonlinearity. The patterns in spike trains appear to reflect genuine nonlinear structure. The limitations of these results are also discussed. The results presented in this article do not, of themselves, establish the presence of a fine-structure encoding of neural information. PMID:8046447

  6. 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

  7. Synchrotron FTIR micro-spectroscopy study of the rat hippocampal formation after pilocarpine-evoked seizures.

    PubMed

    Chwiej, J; Dulinska, J; Janeczko, K; Dumas, P; Eichert, D; Dudala, J; Setkowicz, Z

    2010-10-01

    In the present work, synchrotron radiation Fourier transform infrared (SRFTIR) micro-spectroscopy and imaging were used for topographic and semi-quantitative biochemical analysis of rat brain tissue in cases of pilocarpine-induced epilepsy. The tissue samples were analyzed with a beam defined by small apertures and spatial resolution steps of 10 microm which allowed us to probe the selected cellular layers of hippocampal formation. Raster scanning of the samples has generated 2D chemical cartographies revealing the distribution of proteins, lipids and nucleic acids. Spectral analysis has shown changes in the saturation level of phospholipids and relative secondary structure of proteins. Special interest was put in the analysis of two areas of the hippocampal formation (sector 3 of the Ammon's horn, CA3 and dentate gyrus, DG) in which elemental abnormalities were observed during our previous studies. Statistically significant increase in the saturation level of phospholipids (increased ratio of the absorption intensities at around 2921 and 2958 cm(-1)) as well as conformational changes of proteins (beta-type structure discrepancies as shown by the increased ratio of the absorbance intensities at around 1631 and 1657 cm(-1) as well as the ratio of the absorbance at 1548 and 1657 cm(-1)) were detected in pyramidal cells of CA3 area as well as in the multiform and molecular layers of DG. The findings presented here suggest that abnormalities in the protein secondary structure and increases in the level of phospholipid saturation could be involved in mechanisms of neurodegenerative changes following the oxidative stress evoked in brain areas affected by pilocarpine-induced seizures. PMID:20362662

  8. Transmeningeal muscimol can prevent focal EEG seizures in the rat neocortex without stopping multineuronal activity in the treated area.

    PubMed

    Ludvig, Nandor; Tang, Hai M; Artan, N Sertac; Mirowski, Piotr; Medveczky, Geza; Baptiste, Shirn L; Darisi, Sindhu; Kuzniecky, Ruben I; Devinsky, Orrin; French, Jacqueline A

    2011-04-18

    Muscimol has potent antiepileptic efficacy after transmeningeal administration in animals. However, it is unknown whether this compound stops local neuronal firing at concentrations that prevent seizures. The purpose of this study was to test the hypothesis that epidurally administered muscimol can prevent acetylcholine (Ach)-induced focal seizures in the rat neocortex without causing cessation of multineuronal activity. Rats were chronically implanted with a modified epidural cup over the right frontal cortex, with microelectrodes positioned underneath the cup. In each postsurgical experimental day, either saline or 0.005-, 0.05-, 0.5- or 5.0-mM muscimol was delivered through the cup, followed by a 20-min monitoring of the multineuronal activity and the subsequent delivery of Ach in the same way. Saline and muscimol pretreatment in the concentration range of 0.005-0.05 mM did not prevent EEG seizures. In contrast, 0.5-mM muscimol reduced the average EEG Seizure Duration Ratio value from 0.30±0.04 to 0. At this muscimol concentration, the average baseline multineuronal firing rate of 10.9±4.4 spikes/s did not change significantly throughout the 20-min pretreatment. Muscimol at 5.0mM also prevented seizures, but decreased significantly the baseline multineuronal firing rate of 7.0±1.8 to 3.7±0.9 spikes/s in the last 10 min of pretreatment. These data indicate that transmeningeal muscimol in a submillimolar concentration range can prevent focal neocortical seizures without stopping multineuronal activity in the treated area, and thus this treatment is unlikely to interrupt local physiological functions. PMID:21338591

  9. 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.

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

    PubMed

    Shayegh, F; Sadri, S; Amirfattahi, R; Ansari-Asl, K; Bellanger, J J; Senhadji, L

    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. 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

  12. CA3 Synaptic Silencing Attenuates Kainic Acid-Induced Seizures and Hippocampal Network Oscillations123

    PubMed Central

    Yu, Lily M. Y.; Wintzer, Marie E.

    2016-01-01

    Abstract Epilepsy is a neurological disorder defined by the presence of seizure activity, manifest both behaviorally and as abnormal activity in neuronal networks. An established model to study the disorder in rodents is the systemic injection of kainic acid, an excitatory neurotoxin that at low doses quickly induces behavioral and electrophysiological seizures. Although the CA3 region of the hippocampus has been suggested to be crucial for kainic acid-induced seizure, because of its strong expression of kainate glutamate receptors and its high degree of recurrent connectivity, the precise role of excitatory transmission in CA3 in the generation of seizure and the accompanying increase in neuronal oscillations remains largely untested. Here we use transgenic mice in which CA3 pyramidal cell synaptic transmission can be inducibly silenced in the adult to demonstrate CA3 excitatory output is required for both the generation of epileptiform oscillatory activity and the progression of behavioral seizures. PMID:27022627

  13. 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

  14. Cleavage of bid may amplify caspase-8-induced neuronal death following focally evoked limbic seizures.

    PubMed

    Henshall, D C; Bonislawski, D P; Skradski, S L; Lan, J Q; Meller, R; Simon, R P

    2001-08-01

    The mechanism by which seizures induce neuronal death is not completely understood. Caspase-8 is a key initiator of apoptosis via extrinsic, death receptor-mediated pathways; we therefore investigated its role in mediating seizure-induced neuronal death evoked by unilateral kainic acid injection into the amygdala of the rat, terminated after 40 min by diazepam. We demonstrate that cleaved (p18) caspase-8 was detectable immediately following seizure termination coincident with an increase in cleavage of the substrate Ile-Glu-Thr-Asp (IETD)-p-nitroanilide and the appearance of cleaved (p15) Bid. Expression of Fas and FADD, components of death receptor signaling, was increased following seizures. In vivo intracerebroventricular z-IETD-fluoromethyl ketone administration significantly reduced seizure-induced activities of caspases 8, 9, and 3 as well as reducing Bid and caspase-9 cleavage, cytochrome c release, DNA fragmentation, and neuronal death. These data suggest that intervention in caspase-8 and/or death receptor signaling may confer protection on the brain from the injurious effects of seizures. PMID:11493022

  15. Early detection of human focal seizures based on cortical multiunit activity.

    PubMed

    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

  16. 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

  17. Impaired neuronal KCC2 function by biallelic SLC12A5 mutations in migrating focal seizures and severe developmental delay.

    PubMed

    Saitsu, Hirotomo; Watanabe, Miho; Akita, Tenpei; Ohba, Chihiro; Sugai, Kenji; Ong, Winnie Peitee; Shiraishi, Hideaki; Yuasa, Shota; Matsumoto, Hiroshi; Beng, Khoo Teik; Saitoh, Shinji; Miyatake, Satoko; Nakashima, Mitsuko; Miyake, Noriko; Kato, Mitsuhiro; Fukuda, Atsuo; Matsumoto, Naomichi

    2016-01-01

    Epilepsy of infancy with migrating focal seizures (EIMFS) is one of the early-onset epileptic syndromes characterized by migrating polymorphous focal seizures. Whole exome sequencing (WES) in ten sporadic and one familial case of EIMFS revealed compound heterozygous SLC12A5 (encoding the neuronal K(+)-Cl(-) co-transporter KCC2) mutations in two families: c.279 + 1G > C causing skipping of exon 3 in the transcript (p.E50_Q93del) and c.572 C >T (p.A191V) in individuals 1 and 2, and c.967T > C (p.S323P) and c.1243 A > G (p.M415V) in individual 3. Another patient (individual 4) with migrating multifocal seizures and compound heterozygous mutations [c.953G > C (p.W318S) and c.2242_2244del (p.S748del)] was identified by searching WES data from 526 patients and SLC12A5-targeted resequencing data from 141 patients with infantile epilepsy. Gramicidin-perforated patch-clamp analysis demonstrated strongly suppressed Cl(-) extrusion function of E50_Q93del and M415V mutants, with mildly impaired function of A191V and S323P mutants. Cell surface expression levels of these KCC2 mutants were similar to wildtype KCC2. Heterologous expression of two KCC2 mutants, mimicking the patient status, produced a significantly greater intracellular Cl(-) level than with wildtype KCC2, but less than without KCC2. These data clearly demonstrated that partially disrupted neuronal Cl(-) extrusion, mediated by two types of differentially impaired KCC2 mutant in an individual, causes EIMFS. PMID:27436767

  18. Impaired neuronal KCC2 function by biallelic SLC12A5 mutations in migrating focal seizures and severe developmental delay

    PubMed Central

    Saitsu, Hirotomo; Watanabe, Miho; Akita, Tenpei; Ohba, Chihiro; Sugai, Kenji; Ong, Winnie Peitee; Shiraishi, Hideaki; Yuasa, Shota; Matsumoto, Hiroshi; Beng, Khoo Teik; Saitoh, Shinji; Miyatake, Satoko; Nakashima, Mitsuko; Miyake, Noriko; Kato, Mitsuhiro; Fukuda, Atsuo; Matsumoto, Naomichi

    2016-01-01

    Epilepsy of infancy with migrating focal seizures (EIMFS) is one of the early-onset epileptic syndromes characterized by migrating polymorphous focal seizures. Whole exome sequencing (WES) in ten sporadic and one familial case of EIMFS revealed compound heterozygous SLC12A5 (encoding the neuronal K+-Cl− co-transporter KCC2) mutations in two families: c.279 + 1G > C causing skipping of exon 3 in the transcript (p.E50_Q93del) and c.572 C >T (p.A191V) in individuals 1 and 2, and c.967T > C (p.S323P) and c.1243 A > G (p.M415V) in individual 3. Another patient (individual 4) with migrating multifocal seizures and compound heterozygous mutations [c.953G > C (p.W318S) and c.2242_2244del (p.S748del)] was identified by searching WES data from 526 patients and SLC12A5-targeted resequencing data from 141 patients with infantile epilepsy. Gramicidin-perforated patch-clamp analysis demonstrated strongly suppressed Cl− extrusion function of E50_Q93del and M415V mutants, with mildly impaired function of A191V and S323P mutants. Cell surface expression levels of these KCC2 mutants were similar to wildtype KCC2. Heterologous expression of two KCC2 mutants, mimicking the patient status, produced a significantly greater intracellular Cl− level than with wildtype KCC2, but less than without KCC2. These data clearly demonstrated that partially disrupted neuronal Cl− extrusion, mediated by two types of differentially impaired KCC2 mutant in an individual, causes EIMFS. PMID:27436767

  19. Hypocalcemic focal seizures in a one-month-old infant of a mother with a low circulating level of vitamin D.

    PubMed

    Oki, J; Takedatsu, M; Itoh, J; Yano, K; Cho, K; Okuno, A

    1991-01-01

    We present a case of a one-month-old infant with hypocalcemia and rickets, with symptoms of focal seizures. The ictal EEG showed left occipital spikes spreading over all of the left hemisphere. From the laboratory studies, we concluded that a low maternal circulating level of vitamin D would cause infantile hypocalcemia and rickets, while immature renal response to parathyroid hormone and transient hypoparathyroidism in infancy would induce hyperphosphatemia. Hypocalcemia may be an important factor in the cause of focal seizures which start even after the age of one month. Further, investigation of maternal vitamin D levels should be done in infantile hypocalcemia. PMID:1892219

  20. Ictal Spread of Medial Temporal Lobe Seizures With and Without Secondary Generalization: An Intracranial EEG Analysis

    PubMed Central

    Yoo, Ji Yeoun; Farooque, Pue; Chen, William; Youngblood, Mark W.; Zaveri, Hitten P.; Gerrard, Jason L.; Spencer, Dennis D.; Hirsch, Lawrence J.; Blumenfeld, Hal

    2013-01-01

    Summary Objective Secondary generalization of seizures has devastating consequences for patient safety and quality of life. The aim of this intracranial EEG (icEEG) study was to investigate the differences in onset and propagation patterns of temporal lobe seizures that remained focal vs. those with secondary generalization in order to better understand the mechanism of secondary generalization. Methods A total of 39 seizures were analyzed in 9 patients who met the following criteria: 1) icEEG-video monitoring with at least 1 secondarily generalized tonic clonic seizure (GTC), 2) pathologically proven hippocampal sclerosis, and 3) no seizures for at least 1 year after anteromedial temporal lobe resection. Seizures were classified as focal or secondary generalized by behavioral analysis of video. Onset and propagation patterns were compared by analysis of icEEG. Results We obtained data from 22 focal seizures without generalization (FS), and 17 GTC. Seizure onset patterns did not differ between FS and GTCs, but there were differences in later propagation. All seizures started with low voltage fast activity except 7 seizures in one patient (6 FS, 1 GTC), which started with sharply contoured theta activity. 15 of 39 seizures started from the hippocampus and 24 seizures (including 6 seizures in a patient without hippocampal contacts) started from other medial temporal lobe areas. We observed involvement or more prominent activation of the posterior-lateral temporal regions in GTCs prior to propagation to the other cortical regions, vs. FS which had no involvement or less prominent activation of the posterior lateral temporal cortex. Occipital contacts were not involved at the time of clinical secondary generalization. Significance The posterior-lateral temporal cortex may serve as an important “gateway” controlling propagation of medial temporal lobe seizures to other cortical regions. Identifying the mechanisms of secondary generalization of focal seizures may

  1. Amygdala kindling-induced seizures selectively impair spatial memory. 2. Effects on hippocampal neuronal and glial muscarinic acetylcholine receptor.

    PubMed

    Beldhuis, H J; Everts, H G; Van der Zee, E A; Luiten, P G; Bohus, B

    1992-10-01

    The muscarinic acetylcholine receptor is linked via hydrolysis of phosphoinositides to the protein kinase C pathway. In a preceding paper (Beldhuis, H. J. A., H. G. J. Everts, E. A. Vander Zee, P. G. M. Luiten, and B. Bohus (1992) Amygdala kindling-induced seizures selectively impair spatial memory. 1. Behavioral characteristics and effects on hippocampal neuronal protein kinase C isoforms. Hippocampus 2:397-410), the role of different isoforms of protein kinase C in neurobiological processes associated with plasticity was studied using both a spatial learning paradigm and amygdala kindling in the rat. This study extended the findings on protein kinase C activity to the level of the muscarinic acetylcholine receptor. Rats were trained in a spatial learning paradigm and kindled simultaneously in the amygdala to develop generalized motor convulsions. Control rats were trained only in the spatial learning paradigm to acquire stable working and reference memory performance. Alteration in the expression of the muscarinic acetylcholine receptor was investigated using a monoclonal antibody to muscarinic acetylcholine receptor proteins. Trained control rats that were exposed repeatedly to the spatial learning paradigm showed an increase in immunoreactivity for the muscarinic acetylcholine receptor located in the same hippocampal regions in which the protein kinase C activity was increased. In fully kindled rats, however, this increase located in principal neurons was absent, whereas expression of muscarinic acetylcholine receptor proteins was increased in hippocampal astrocytes. Moreover, fully kindled rats showed an impairment in reference memory performance as compared to trained control rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1308197

  2. Mouse hippocampal phosphorylation footprint induced by generalized seizures: Focus on ERK, mTORC1 and Akt/GSK-3 pathways.

    PubMed

    Gangarossa, Giuseppe; Sakkaki, Sophie; Lory, Philippe; Valjent, Emmanuel

    2015-12-17

    Exacerbated hippocampal activity has been associated to critical modifications of the intracellular signaling pathways. We have investigated rapid hippocampal adaptive responses induced by maximal electroshock seizure (MES). Here, we demonstrate that abnormal and exacerbated hippocampal activity induced by MES triggers specific and temporally distinct patterns of phosphorylation of extracellular signal-related kinase (ERK), mammalian target of rapamycin complex (mTORC) and Akt/glycogen synthase kinase-3 (Akt/GSK-3) pathways in the mouse hippocampus. While the ERK pathway is transiently activated, the mTORC1 cascade follows a rapid inhibition followed by a transient activation. This rebound of mTORC1 activity leads to the selective phosphorylation of p70S6K, which is accompanied by an enhanced phosphorylation of the ribosomal subunit S6. In contrast, the Akt/GSK-3 pathway is weakly altered. Finally, MES triggers a rapid upregulation of several plasticity-associated genes as a consequence exacerbated hippocampal activity. The results reported in the present study are reminiscent of the one observed in other models of generalized seizures, thus defining a common molecular footprint induced by intense and aberrant hippocampal activities. PMID:26545981

  3. Conditional Disabled-1 Deletion in Mice Alters Hippocampal Neurogenesis and Reduces Seizure Threshold

    PubMed Central

    Korn, Matthew J.; Mandle, Quinton J.; Parent, Jack M.

    2016-01-01

    Many animal models of temporal lobe epilepsy (TLE) exhibit altered neurogenesis arising from progenitors within the dentate gyrus subgranular zone (SGZ). Aberrant integration of new neurons into the existing circuit is thought to contribute to epileptogenesis. In particular, adult-born neurons that exhibit ectopic migration and hilar basal dendrites (HBDs) are suggested to be pro-epileptogenic. Loss of reelin signaling may contribute to these morphological changes in patients with epilepsy. We previously demonstrated that conditional deletion of the reelin adaptor protein, disabled-1 (Dab1), from postnatal mouse SGZ progenitors generated dentate granule cells (DGCs) with abnormal dendritic development and ectopic placement. To determine whether the early postnatal loss of reelin signaling is epileptogenic, we conditionally deleted Dab1 in neural progenitors and their progeny on postnatal days 7–8 and performed chronic video-EEG recordings 8–10 weeks later. Dab1-deficient mice did not have spontaneous seizures but exhibited interictal epileptiform abnormalities and a significantly reduced latency to pilocarpine-induced status epilepticus. After chemoconvulsant treatment, over 90% of mice deficient for Dab1 developed generalized motor convulsions with tonic-clonic movements, rearing, and falling compared to <20% of wild-type mice. Recombination efficiency, measured by Cre reporter expression, inversely correlated with time to the first sustained seizure. These pro-epileptogenic changes were associated with decreased neurogenesis and increased numbers of hilar ectopic DGCs. Interestingly, neurons co-expressing the Cre reporter comprised a fraction of these hilar ectopic DGCs cells, suggesting a non-cell autonomous effect for the loss of reelin signaling. We also noted a dispersion of the CA1 pyramidal layer, likely due to hypomorphic effects of the conditional Dab1 allele, but this abnormality did not correlate with seizure susceptibility. These findings suggest

  4. Fluvoxamine alleviates seizure activity and downregulates hippocampal GAP-43 expression in pentylenetetrazole-kindled mice: role of 5-HT3 receptors.

    PubMed

    Alhaj, Momen W; Zaitone, Sawsan A; Moustafa, Yasser M

    2015-06-01

    Epilepsy has been documented to lead to many changes in the nervous system including cell loss and mossy fiber sprouting. Neuronal loss and aberrant neuroplastic changes in the dentate gyrus of the hippocampus have been identified in the pentylenetetrazole (PTZ) kindling model. Antiseizure activity of selective serotonin reuptake inhibitors has been reported in several studies. In the current study, the protective effect of fluvoxamine against PTZ-kindling was investigated in terms of seizure scores, neuronal loss, and regulation of hippocampal neuroplasticity. Further, the role of 5-HT3 receptors was determined. Kindling was induced by repeated injections of PTZ (35 mg/kg) thrice weekly, for a total of 13 injections. One hundred male albino mice were allocated into 10 groups: (1) saline, (2) PTZ, (3) diazepam (1 mg/kg)+PTZ, (4-6) fluvoxamine (5, 10 or 20 mg/kg)+PTZ, (7) ondansetron+fluvoxamine (20 mg/kg)+PTZ, (8) ondansetron+PTZ group, (9) ondansetron (2 mg/kg, i.p.)+saline, and (10) fluvoxamine (20 mg/kg)+saline. PTZ-kindled mice showed high seizure activity, hippocampal neuronal loss, and expression of growth-associated phosphoprotein (GAP-43) compared with saline-treated mice. Repeated administration of fluvoxamine (20 mg/kg) in PTZ-kindled mice suppressed seizure scores, protected against hippocampal neuronal loss, and downregulated GAP-43 expression, without producing any signs of the 5-HT syndrome in healthy rats. Importantly, pretreatment with a selective 5-HT3 receptor blocker (ondansetron) attenuated the aforementioned effects of fluvoxamine. In conclusion, the ameliorating effect of fluvoxamine on hippocampal neurons and neuroplasticity in PTZ-kindled mice was, at least in part, dependent on enhancement of hippocampal serotoninergic transmission at 5-HT3 receptors. PMID:25590967

  5. 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. PMID:26709877

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

    PubMed

    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 Mg(2+) 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. [Eslicarbazepine acetate: a novel therapeutic alternative in the treatment of focal seizures].

    PubMed

    Mauri-Llerda, José A

    2012-05-01

    Epilepsy is one of the most common neurological diseases. In recent years an important number of drugs have been added to the therapeutic options we have available to us. With the aim of offering an optimal clinical effectiveness, the mechanisms of action or chemical structures of the antiepileptic drugs recently introduced onto the market have been modified with respect to the first, so-called classical or conventional, antiepileptics. Eslicarbazepine acetate belongs to this group of recently incorporated pharmaceuticals and is a novel single daily dose voltage-gated sodium channel blocker, which acts selectively in groups of rapid-activation neurons. It has been approved for indication in associated therapy in adults with partial onset seizures, with or without secondary generalisation. It is widely metabolised to eslicarbazepine and, to a lesser extent, to R-licarbazepine and oxcarbazepine. In 800 mg and 1200 mg doses it has been shown to bring about a significant reduction in a high percentage of patients with refractory epilepsy in simultaneous treatment with up to three antiepileptic drugs, and this effectiveness is maintained in open follow-up studies lasting up to a year. It is generally speaking well-tolerated; most of the adverse side-effects range in intensity from mild to moderate, and the percentage of patients who withdraw from treatment for this reason is low. Eslicarbazepine acetate is an alternative treatment in associated therapy in patients with partial epilepsy who do not respond adequately to treatment in monotherapy. PMID:22532219

  8. 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. PMID:26341542

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

    PubMed

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

    2016-07-01

    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

  10. Interictal Hippocampal Spiking Influences the Occurrence of Hippocampal Sleep Spindles

    PubMed Central

    Frauscher, Birgit; Bernasconi, Neda; Caldairou, Benoit; von Ellenrieder, Nicolás; Bernasconi, Andrea; Gotman, Jean; Dubeau, François

    2015-01-01

    Objectives: The significance of hippocampal sleep spindles and their relation to epileptic activity is still a matter of controversy. Hippocampal spindles have been considered a physiological phenomenon, an evoked response to afferent epileptic discharges, or even the expression of an epileptic manifestation. To address this question, we investigated the presence and rate of hippocampal spindles in focal pharmacoresistant epilepsy patients undergoing scalp-intracerebral electroencephalography (EEG). Design: Sleep recording with scalp-intracerebral EEG. Setting: Tertiary referral epilepsy center. Patients: Twenty-five epilepsy patients (extratemporal: n = 6, temporal: n = 15, and multifocal including the temporal lobe: n = 4). Interventions: N/A. Measurements and Results: We analyzed associations between hippocampal spindles and hippocampal electrophysiological findings (interictal spiking, seizure onset zone) and magnetic resonance imaging volumetry. Sixteen of 25 patients (64%) had hippocampal spindles (extratemporal epilepsy: 6/6; temporal epilepsy: 10/15; and multifocal epilepsy: 0/4; P = 0.005). Median spindle rate was 0.6 (range, 0.1–8.6)/min in nonrapid eye movement sleep. Highest spindle rates were found in hippocampi of patients with extratemporal epilepsy (P < 0.001). A negative association was found between hippocampal spiking activity and spindle rate (P = 0.003). We found no association between the presence (n = 21) or absence (n = 17) of hippocampal seizure onset zone and hippocampal spindle rate (P = 0.114), and between a normal (n = 30) or atrophic (n = 8) hippocampus and hippocampal spindle rate (P = 0.195). Conclusions: Hippocampal spindles represent a physiological phenomenon, with an expression that is diminished in epilepsy affecting the temporal lobe. Hippocampal spiking lowered the rate of hippocampal spindles, suggesting that epileptic discharges may at least in part be a transformation of these physiological events, similar to the

  11. Cannabidiol Post-Treatment Alleviates Rat Epileptic-Related Behaviors and Activates Hippocampal Cell Autophagy Pathway Along with Antioxidant Defense in Chronic Phase of Pilocarpine-Induced Seizure.

    PubMed

    Hosseinzadeh, Mahshid; Nikseresht, Sara; Khodagholi, Fariba; Naderi, Nima; Maghsoudi, Nader

    2016-04-01

    Abnormal and sometimes severe behavioral and molecular symptoms are usually observed in epileptic humans and animals. To address this issue, we examined the behavioral and molecular aspects of seizure evoked by pilocarpine. Autophagy can promote both cell survival and death, but there are controversial reports about the neuroprotective or neurodegenerative effects of autophagy in seizure. Cannabidiol has anticonvulsant properties in some animal models when used as a pretreatment. In this study, we investigated alteration of seizure scores, autophagy pathway proteins, and antioxidant status in hippocampal cells during the chronic phase of pilocarpine-induced epilepsy after treatment with cannabidiol. Cannabidiol (100 ng, intracerebroventricular injection) delayed the chronic phase of epilepsy. Single administration of cannabidiol during the chronic phase of seizure significantly diminished seizure scores such as mouth clonus, head nodding, monolateral and bilateral forelimb clonus and increased the activity of catalase enzyme and reduced glutathione content. Such a protective effect in the behavioral scores of epileptic rats was also observed after repeated administrations of cannabidiol at the onset of the silent phase. Moreover, the amount of Atg7, conjugation of Atg5/12, Atg12, and LC3II/LC3I ratio increased significantly in epileptic rats treated with repeated injections of cannabidiol. In short, our results suggest that post-treatment of Cannabidiol could enhance the induction of autophagy pathway and antioxidant defense in the chronic phase of epilepsy, which could be considered as the protective mechanisms of cannabidiol in a temporal lobe epilepsy model. PMID:26738731

  12. Omega 3 polyunsaturated fatty acids enhance the protective effect of levetiracetam against seizures, cognitive impairment and hippocampal oxidative DNA damage in young kindled rats.

    PubMed

    Abdel-Wahab, Basel A; Shaikh, Ibrahim A; Khateeb, Masood M; Habeeb, Shafiuddin M

    2015-08-01

    Levetiracetam (LEV) is a unique, effective, relatively safe antiepileptic drug that preferentially interacts with synaptic vesicle protein 2A (SV2A). This study aimed to explore the effect of combined treatment of LEV with omega 3 (OM3) on cognitive impairment and hippocampal oxidative stress and DNA damage induced by seizures in the PTZ-kindled young rat model. Cognitive functions, biomarkers of oxidative stress, and DNA damage were assessed in PTZ-kindled young rats pretreated with single and combined treatment of LEV (30mg/kg, i.p.) and OM3 (200mg/kg, p.o.). Pretreatment with LEV and OM3 at the tested doses significantly attenuated PTZ-induced seizures and decreased cognitive impairment in both passive avoidance and elevated plus maze tests in the PTZ-kindled rats. Moreover, the increase in hippocampal glutamate, malondialdehyde and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels, as well as the decrease in reduced glutathione (GSH) levels and GSH-peroxidase and superoxide dismutase activities induced by PTZ kindling, significantly decreased. These effects were higher with combined treatment of LEV with OM3 and significantly more than the observed effects of single LEV or OM3. In conclusion, the combined treatment of LEV with OM3 is more effective in seizure control and alleviating the cognitive impairment induced by PTZ kindling in the young rat model, the effects that result from the decrease in hippocampal oxidative stress and DNA damage which can be attributed to the antioxidant properties of both LEV and OM3. These results may be promising for the use of LEV and OM3 combination in the treatment of epileptic children. PMID:26044965

  13. Left Hippocampal Pathology Is Associated with Atypical Language Lateralization in Patients with Focal Epilepsy

    ERIC Educational Resources Information Center

    Weber, Bernd; Wellmer, Jorg; Reuber, Markus; Mormann, Florian; Weis, Susanne; Urbach, Horst; Ruhlmann, Jurgen; Elger, Christian E.; Fernandez, Guillen

    2006-01-01

    It is well recognized that the incidence of atypical language lateralization is increased in patients with focal epilepsy. The hypothesis that shifts in language dominance are particularly likely when epileptic lesions are located in close vicinity to the so-called language-eloquent areas rather than in more remote brain regions such as the…

  14. Phase-Amplitude Coupling Is Elevated in Deep Sleep and in the Onset Zone of Focal Epileptic Seizures.

    PubMed

    Amiri, Mina; Frauscher, Birgit; Gotman, Jean

    2016-01-01

    The interactions between different EEG frequency bands have been widely investigated in normal and pathologic brain activity. Phase-amplitude coupling (PAC) is one of the important forms of this interaction where the amplitude of higher frequency oscillations is modulated by the phase of lower frequency activity. Here, we studied the dynamic variations of PAC of high (gamma and ripple) and low (delta, theta, alpha, and beta) frequency bands in patients with focal epilepsy in different sleep stages during the interictal period, in an attempt to see if coupling is different in more or less epileptogenic regions. Sharp activities were excluded to avoid their effect on the PAC. The results revealed that the coupling intensity was generally the highest in stage N3 of sleep and the lowest in rapid eye movement sleep. We also compared the coupling strength in different regions [seizure onset zone (SOZ), exclusively irritative zone, and normal zone]. PAC between high and low frequency rhythms was found to be significantly stronger in the SOZ compared to normal regions. Also, the coupling was generally more elevated in spiking channels outside the SOZ than in normal regions. We also examined how the power in the delta band correlates to the PAC, and found a mild but statistically significant correlation between slower background activity in epileptic channels and the elevated coupling in these channels. The results suggest that an elevated PAC may reflect some fundamental abnormality, even after exclusion of sharp activities and even in the interictal period. PAC may therefore contribute to understanding the underlying dynamics of epileptogenic brain regions. PMID:27536227

  15. Phase-Amplitude Coupling Is Elevated in Deep Sleep and in the Onset Zone of Focal Epileptic Seizures

    PubMed Central

    Amiri, Mina; Frauscher, Birgit; Gotman, Jean

    2016-01-01

    The interactions between different EEG frequency bands have been widely investigated in normal and pathologic brain activity. Phase-amplitude coupling (PAC) is one of the important forms of this interaction where the amplitude of higher frequency oscillations is modulated by the phase of lower frequency activity. Here, we studied the dynamic variations of PAC of high (gamma and ripple) and low (delta, theta, alpha, and beta) frequency bands in patients with focal epilepsy in different sleep stages during the interictal period, in an attempt to see if coupling is different in more or less epileptogenic regions. Sharp activities were excluded to avoid their effect on the PAC. The results revealed that the coupling intensity was generally the highest in stage N3 of sleep and the lowest in rapid eye movement sleep. We also compared the coupling strength in different regions [seizure onset zone (SOZ), exclusively irritative zone, and normal zone]. PAC between high and low frequency rhythms was found to be significantly stronger in the SOZ compared to normal regions. Also, the coupling was generally more elevated in spiking channels outside the SOZ than in normal regions. We also examined how the power in the delta band correlates to the PAC, and found a mild but statistically significant correlation between slower background activity in epileptic channels and the elevated coupling in these channels. The results suggest that an elevated PAC may reflect some fundamental abnormality, even after exclusion of sharp activities and even in the interictal period. PAC may therefore contribute to understanding the underlying dynamics of epileptogenic brain regions. PMID:27536227

  16. SIRT5 Deficiency Enhances Susceptibility to Kainate-Induced Seizures and Exacerbates Hippocampal Neurodegeneration not through Mitochondrial Antioxidant Enzyme SOD2

    PubMed Central

    Li, Fengling; Liu, Lei

    2016-01-01

    Epilepsy is a common and serious neurological disorder characterized by occurrence of recurrent spontaneous seizures, and emerging evidences support the association of mitochondrial dysfunction with epilepsy. Sirtuin 5 (SIRT5), localized in mitochondrial matrix, has been considered as an important functional modulator of mitochondria that contributes to ageing and neurological diseases. Our data shows that SIRT5 deficiency strikingly increased mortality rate and severity of response to epileptic seizures, dramatically exacerbated hippocampal neuronal loss and degeneration in mice exposed to Kainate (KA), and triggered more severe reactive astrogliosis. We found that the expression of mitochondrial SIRT5 of injured hippocampus was relatively up-regulated, indicating its potential contribution to the comparably increased survival of these cells and its possible neuroprotective role. Unexpectedly, SIRT5 seems not to apparently alter the decline of antioxidant enzymes superoxide dismutase 2 (SOD2) and glutathione peroxidase (GPx) in hippocampus caused by KA exposure in our paradigm, which indicates the protective role of SIRT5 on seizures and cellular degeneration might through different regulatory mechanism that would be explored in the future. In the present study, we provided strong evidences for the first time to demonstrate the association between SIRT5 and epilepsy, which offers a new understanding of the roles of SIRT5 in mitochondrial functional regulation. The neuroprotection of SIRT5 in KA-induced epileptic seizure and neurodegeneration will improve our current knowledge of the nature of SIRT5 in central nervous system (CNS) and neurological diseases. PMID:27445698

  17. Beneficial Effects of Polygonum multiflorum on Hippocampal Neuronal Cells and Mouse Focal Cerebral Ischemia.

    PubMed

    Ahn, Sung Min; Kim, Yu Ri; Kim, Ha Neui; Shin, Hwa Kyoung; Choi, Byung Tae

    2015-01-01

    Beneficial effects of the water extract of Polygonum multiflorum (WEPM) and their mechanisms were investigated in HT22 hippocampal cells and hippocampus of middle cerebral artery occlusion (MCAO) mice. In HT22 cells against glutamate-induced oxidative stress, pretreatment with WEPM resulted in significantly reduced apoptotic neuronal death. Pretreatment with WEPM resulted in the suppression of ROS accumulation in connection with cellular Ca (2+) level after exposure to glutamate. Treatment with glutamate alone led to suppressed protein level of mature brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP response element binding protein (CREB); however, pretreatment with either WEPM or anti-oxidant N-acetyl-ʟ-cysteine (NAC) resulted in the significant enhancement of levels of these proteins. In addition, levels of mature BDNF expression and CREB phosphorylation were increased by combined treatment with WEPM, NAC, and intracellular Ca (2+) inhibitor BAPTA compared to other treatment groups. In MCAO mice, we confirmed the critical role of mature BDNF expression and CREB phosphorylation by WEPM in the neurons of the hippocampus. Our results suggest that WEPM mainly exerted beneficial effects on hippocampal neurons through the suppression of ROS accumulation and up-regulation of mature BDNF expression and CREB phosphorylation. PMID:26119951

  18. Chronic oleoylethanolamide treatment improves spatial cognitive deficits through enhancing hippocampal neurogenesis after transient focal cerebral ischemia.

    PubMed

    Yang, Li-Chao; Guo, Han; Zhou, Hao; Suo, Da-Qin; Li, Wen-Jun; Zhou, Yu; Zhao, Yun; Yang, Wu-Shuang; Jin, Xin

    2015-04-15

    Oleoylethanolamide (OEA) has been shown to have neuroprotective effects after acute cerebral ischemic injury. The aim of this study was to investigate the effects of chronic OEA treatment on ischemia-induced spatial cognitive impairments, electrophysiology behavior and hippocampal neurogenesis. Daily treatments of 30 mg/kg OEA significantly ameliorated spatial cognitive deficits and attenuated the inhibition of long-term potentiation (LTP) in the middle cerebral artery occlusion (MCAO) rat model. Moreover, OEA administration improved cognitive function in a manner associated with enhanced neurogenesis in the hippocampus. Further study demonstrated that treatment with OEA markedly increased the expressions of brain-derived neurotrophic factor (BDNF) and peroxisome proliferator-activated receptors α (PPARα). Our data suggest that chronic OEA treatment can exert functional recovery of cognitive impairments and neuroprotective effects against cerebral ischemic insult in rats via triggering of neurogenesis in the hippocampus, which supports the therapeutic use of OEA for cerebral ischemia. PMID:25748831

  19. 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. PMID:26286172

  20. Fingolimod (FTY720) improves hippocampal synaptic plasticity and memory deficit in rats following focal cerebral ischemia.

    PubMed

    Nazari, Maryam; Keshavarz, Somaye; Rafati, Ali; Namavar, Mohammad Reza; Haghani, Masoud

    2016-06-01

    Fingolimod (FTY720) is a known sphingosine-1-phosphate (S1P) receptor agonist. Several studies have shown the therapeutic efficacy of FTY720 in neurodegenerative disorders. However, the neuroprotective mechanisms in brain ischemia have not been adequately studied. Therefore, the present study aimed to investigate the effects of FTY720 on the impairment of learning and memory and hippocampal synaptic plasticity induced by middle cerebral artery occlusion (MCAO) in ischemic brain injury. Twenty eight male rats were randomly divided into four groups of control (n=7), sham (n=8), ischemic-reperfusion+vehicle (I/R+V; n=7), and I/R+FTY720 (n=6). After 1h of the occlusion of artery, the filament was gently withdrawn to allow reperfusion for the next 7 days. The animals first received a dose of FTY720 (0.5mg/Kg) or its vehicle (intra-peritoneal) twenty-four hours before surgery in I/R+FTY720 and I/R+V groups, respectively. The administration of FTY720 or its vehicle continued every other day. The passive avoidance test and field potential recording were used for evaluation of learning, memory and synaptic plasticity. The brain infarct volume was measured by triphenyltetrazolim hydrochloride (TTC) staining. MCAO caused infarct damage in the rat's brain tissue. The administration of FTY720 significantly reduced the size of the lesion, improved the memory impairment of MCAO rats, and increased the STL time. In addition, the field potential recording demonstrated a marked reduction in induction of long-term potentiation of MCAO animals. However, administration of FTY720 recovers the magnitude of the LTP without any effects on presynaptic plasticity and neurotransmitter release probability. The results of this study demonstrated that MCAO in rats impairs the retention of passive avoidance tasks and multiple injection of FTY720 improved the memory performance after MCAO by LTP induction via post-synaptic mechanisms. PMID:27066884

  1. The temporal sequence of aura-sensations in patients with complex focal seizures with particular attention to ictal aphasia.

    PubMed Central

    Kanemoto, K; Janz, D

    1989-01-01

    The sequences of aura sensations in 143 patients with complex partial seizures, were analysed with special emphasis on aphasic symptoms. Anxiety, epigastric sensation and visual hallucination were experienced early in the course of the aura, while illusion of familiarity and aphasia occurred late in the course of the aura. Three groups of interconnections of aura sensations were found which corresponded possibly to the types of seizure constellations proposed by Weiser. Close interconnections between impairment of verbal comprehension during seizures and paroxysmal thought disorder, as well as between paroxysmal paraphasia and illusion of familiarity were noted. Paroxysmal aphasia in patients with complex partial seizures was characterised as a positive symptom in contrast to stable aphasia. PMID:2468740

  2. Stimulation of Anterior Thalamic Nuclei Protects Against Seizures and Neuronal Apoptosis in Hippocampal CA3 Region of Kainic Acid-induced Epileptic Rats

    PubMed Central

    Meng, Da-Wei; Liu, Huan-Guang; Yang, An-Chao; Zhang, Kai; Zhang, Jian-Guo

    2016-01-01

    Background: The antiepileptic effect of the anterior thalamic nuclei (ANT) stimulation has been demonstrated; however, its underlying mechanism remains unclear. The aim of this study was to investigate the effect of chronic ANT stimulation on hippocampal neuron loss and apoptosis. Methods: Sixty-four rats were divided into four groups: The control group, the kainic acid (KA) group, the sham-deep brain stimulation (DBS) group, and the DBS group. KA was used to induce epilepsy. Seizure count and latency to the first spontaneous seizures were calculated. Nissl staining was used to analyze hippocampal neuronal loss. Polymerase chain reaction and Western blotting were conducted to assess the expression of caspase-3 (Casp3), B-cell lymphoma-2 (Bcl2), and Bcl2-associated X protein (Bax) in the hippocampal CA3 region. One-way analysis of variance was used to determine the differences between the four groups. Results: The latency to the first spontaneous seizures in the DBS group was significantly longer than that in the KA group (27.50 ± 8.05 vs. 16.38 ± 7.25 days, P = 0.0005). The total seizure number in the DBS group was also significantly reduced (DBS vs. KA group: 11.75 ± 6.80 vs. 23.25 ± 7.72, P = 0.0002). Chronic ANT-DBS reduced neuronal loss in the hippocampal CA3 region (DBS vs. KA group: 23.58 ± 6.34 vs. 13.13 ± 4.00, P = 0.0012). After chronic DBS, the relative mRNA expression level of Casp3 was decreased (DBS vs. KA group: 1.18 ± 0.37 vs. 2.09 ± 0.46, P = 0.0003), and the relative mRNA expression level of Bcl2 was increased (DBS vs. KA group: 0.92 ± 0.21 vs. 0.48 ± 0.16, P = 0.0004). The protein expression levels of CASP3 (DBS vs. KA group: 1.25 ± 0.26 vs. 2.49 ± 0.38, P < 0.0001) and BAX (DBS vs. KA group: 1.57 ± 0.49 vs. 2.80 ± 0.63, P = 0.0012) both declined in the DBS group whereas the protein expression level of BCL2 (DBS vs. KA group: 0.78 ± 0.32 vs. 0.36 ± 0.17, P = 0.0086) increased in the DBS group. Conclusions: This study demonstrated

  3. Stereotactic radiofrequency amygdalohippocampectomy for the treatment of temporal lobe epilepsy: do good neuropsychological and seizure outcomes correlate with hippocampal volume reduction?

    PubMed

    Malikova, Hana; Kramska, Lenka; Liscak, Roman; Vojtech, Zdenek; Prochazka, Tomas; Mareckova, Iva; Lukavsky, Jiri; Druga, Rastislav

    2012-11-01

    Temporal lobe surgery bears the risk of a decline of neuropsychological functions. Stereotactic radiofrequency amygdalohippocampectomy (SAHE) represents an alternative to mesial temporal lobe epilepsy (MTLE) surgery. This study compared neuropsychological results with MRI volumetry of the residual hippocampus. We included 35 patients with drug-resistant MTLE treated by SAHE. MRI volumetry and neuropsychological examinations were performed before and 1 year after SAHE. Each year after SAHE clinical seizure outcome was assessed. One year after SAHE 77% of patients were assessed as Engel Class I, 14% of patients was classified as Engel II and in 9% of patients treatment failed. Two years after SAHE 76% of subjects were classified as Engel Class I, 15% of patients was assessed as Engel II and in 9% of patients treatment failed. Hippocampal volume reduction was 58±17% on the left and 54 ± 27% on the right side. One year after SAHE, intelligence quotients of treated patients increased. Patients showed significant improvement in verbal memory (p=0.039) and the semantic long-term memory subtest (LTM) (p=0.003). Patients treated on the right side improved in verbal memory, delayed recall and LTM. No changes in memory were found in patients treated on the left side. There was a trend between the larger extent of the hippocampal reduction and improvement in visual memory in speech-side operated. PMID:22591753

  4. Long-Term Seizure Suppression and Optogenetic Analyses of Synaptic Connectivity in Epileptic Mice with Hippocampal Grafts of GABAergic Interneurons

    PubMed Central

    Henderson, Katharine W.; Gupta, Jyoti; Tagliatela, Stephanie; Litvina, Elizabeth; Zheng, XiaoTing; Van Zandt, Meghan A.; Woods, Nicholas; Grund, Ethan; Lin, Diana; Royston, Sara; Yanagawa, Yuchio; Aaron, Gloster B.

    2014-01-01

    Studies in rodent epilepsy models suggest that GABAergic interneuron progenitor grafts can reduce hyperexcitability and seizures in temporal lobe epilepsy (TLE). Although integration of the transplanted cells has been proposed as the underlying mechanism for these disease-modifying effects, prior studies have not explicitly examined cell types and synaptic mechanisms for long-term seizure suppression. To address this gap, we transplanted medial ganglionic eminence (MGE) cells from embryonic day 13.5 VGAT-Venus or VGAT-ChR2-EYFP transgenic embryos into the dentate gyrus (DG) of adult mice 2 weeks after induction of TLE with pilocarpine. Beginning 3–4 weeks after status epilepticus, we conducted continuous video-electroencephalographic recording until 90–100 d. TLE mice with bilateral MGE cell grafts in the DG had significantly fewer and milder electrographic seizures, compared with TLE controls. Immunohistochemical studies showed that the transplants contained multiple neuropeptide or calcium-binding protein-expressing interneuron types and these cells established dense terminal arborizations onto the somas, apical dendrites, and axon initial segments of dentate granule cells (GCs). A majority of the synaptic terminals formed by the transplanted cells were apposed to large postsynaptic clusters of gephyrin, indicative of mature inhibitory synaptic complexes. Functionality of these new inhibitory synapses was demonstrated by optogenetically activating VGAT-ChR2-EYFP-expressing transplanted neurons, which generated robust hyperpolarizations in GCs. These findings suggest that fetal GABAergic interneuron grafts may suppress pharmacoresistant seizures by enhancing synaptic inhibition in DG neural circuits. PMID:25274826

  5. Neurogenesis in a young dog with epileptic seizures.

    PubMed

    Borschensky, C M; Woolley, J S; Kipar, A; Herden, C

    2012-09-01

    Epileptic seizures can lead to various reactions in the brain, ranging from neuronal necrosis and glial cell activation to focal structural disorganization. Furthermore, increased hippocampal neurogenesis has been documented in rodent models of acute convulsions. This is a report of hippocampal neurogenesis in a dog with spontaneous epileptic seizures. A 16-week-old epileptic German Shepherd Dog had marked neuronal cell proliferation (up to 5 mitotic figures per high-power field and increased immunohistochemical expression of proliferative cell nuclear antigen) in the dentate gyrus accompanied by microglial and astroglial activation. Some granule cells expressed doublecortin, a marker of immature neurons; mitotically active cells expressed neuronal nuclear antigen. No mitotic figures were found in the brain of age-matched control dogs. Whether increased neurogenesis represents a general reaction pattern of young epileptic dogs should be investigated. PMID:22194355

  6. 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. PMID:25922088

  7. Coexistent arteriovenous malformation and hippocampal sclerosis.

    PubMed

    Prayson, Richard A; O'Toole, Elizabeth E

    2016-06-01

    Cavernous angiomas or cavernomas have been occasionally described in patients presenting with medically intractable epilepsy. Reports of cavernomas associated with a second pathology potentially causative of seizures have rarely been documented; most commonly, the second pathology is focal cortical dysplasia or less frequently, hippocampal sclerosis. To our knowledge, cases of arteriovenous malformation arising in this clinical setting and associated with hippocampal sclerosis have not been previously described. We report a 56-year-old woman who initially presented at age 24years with staring spells. Imaging studies revealed an arteriovenous malformation in the right parietal lobe. At age 51years, she represented with signs and symptoms related to a hemorrhage from the malformation. The patient underwent Gamma Knife radiosurgery (Elekta AB, Stockholm, Sweden) of the lesion. She subsequently developed seizures, refractory to medical management. MRI studies showed atrophy in the right hippocampus. She underwent resection of the right parietal lobe and hippocampus. Histopathologic examination of the right parietal lesion revealed an arteriovenous malformation marked by focally prominent vascular sclerosis, calcification and adjacent hemosiderin deposition. The hippocampus was marked by prominent neuronal loss and gliosis in the CA1 region, consistent with CA1 sclerosis or hippocampal sclerosis International League Against Epilepsy type 2. PMID:26899356

  8. Tuberous sclerosis complex coexistent with hippocampal sclerosis.

    PubMed

    Lang, Min; Prayson, Richard A

    2016-02-01

    Tuberous sclerosis and hippocampal sclerosis are both well-defined entities associated with medically intractable epilepsy. To our knowledge, there has been only one prior case of these two pathologies being co-existent. We report a 7-month-old boy who presented with intractable seizures at 2 months of age. MRI studies showed diffuse volume loss in the brain with bilateral, multiple cortical tubers and subcortical migration abnormalities. Subependymal nodules were noted without subependymal giant cell astrocytoma. Genetic testing revealed TSC2 and PRD gene deletions. Histopathology of the hippocampus showed CA1 sclerosis marked by loss of neurons in the CA1 region. Sections from the temporal, parietal and occipital lobes showed multiple cortical tubers characterized by cortical architectural disorganization, gliosis, calcifications and increased number of large balloon cells. Focal white matter balloon cells and spongiform changes were also present. The patient underwent resection of the right fronto-parietal lobe and a subsequent resection of the right temporal, parietal and occipital lobes. The patient is free of seizures on anti-epileptic medication 69 months after surgery. Although hippocampal sclerosis is well documented to be associated with coexistent focal cortical dysplasia, the specific co-existence of cortical tubers and hippocampal sclerosis appears to be rare. PMID:26498091

  9. The role of IL-1β and glutamate in the effects of lipopolysaccharide on the hippocampal electrical kindling of seizures.

    PubMed

    Kołosowska, Karolina; Maciejak, Piotr; Szyndler, Janusz; Turzyńska, Danuta; Sobolewska, Alicja; Płaźnik, Adam

    2016-09-15

    In our study, we used rapid electrical hippocampal kindling and in vivo microdialysis methods to assess the involvement of inflammatory mediators: lipopolysaccharide (LPS) and proinflammatory interleukin-1β (IL-1β) in mechanisms of epileptogenesis. We observed, that both, LPS and IL-1β, administered into stimulated hippocampus, accelerated kindling process. LPS also increased the expression of IL-1β in stimulated hippocampus in kindled rats. In vivo acute LPS perfusion, via a microdialysis cannula implanted into the naïve rat's hippocampus, produced an increase in extracellular glutamate release. We suppose, that particularly IL-1β action and increased glutamate concentration may significantly contribute to LPS effects on kindling development. PMID:27609288

  10. Focal and Generalized Patterns of Cerebral Cortical Veins Due to Non-Convulsive Status Epilepticus or Prolonged Seizure Episode after Convulsive Status Epilepticus – A MRI Study Using Susceptibility Weighted Imaging

    PubMed Central

    Verma, Rajeev Kumar; Abela, Eugenio; Schindler, Kaspar; Krestel, Heinz; Springer, Elisabeth; Huber, Adrian; Weisstanner, Christian; Hauf, Martinus; Gralla, Jan; Wiest, Roland

    2016-01-01

    Objective The aim of this study was to investigate variant patterns of cortical venous oxygenation during status epilepticus (SE) using susceptibility-weighted imaging (SWI). Methods We analyzed magnetic resonance imaging (MRI) scans of 26 patients with clinically witnessed prolonged seizures and/or EEG-confirmed SE. All MRI exams encompassed SWI, dynamic susceptibility contrast perfusion MRI (MRI-DSC) and diffusion-weighted imaging (DWI). We aimed to identify distinct patterns of SWI signal alterations that revealed regional or global increases of cerebral blood flow (CBF) and DWI restrictions. We hypothesized that SWI-related oxygenation patterns reflect ictal or postictal patterns that resemble SE or sequelae of seizures. Results Sixteen patients were examined during nonconvulsive status epilepticus (NCSE) as confirmed by EEG, a further ten patients suffered from witnessed and prolonged seizure episode ahead of imaging without initial EEG. MRI patterns of 15 of the 26 patients revealed generalized hyperoxygenation by SWI in keeping with either global or multifocal cortical hyperperfusion. Eight patients revealed a focal hyperoxygenation pattern related to focal CBF increase and three patients showed a focal deoxygenation pattern related to focal CBF decrease. Conclusions SWI-related hyper- and deoxygenation patterns resemble ictal and postictal CBF changes within a range from globally increased to focally decreased perfusion. In all 26 patients the SWI patterns were in keeping with ictal hyperperfusion (hyperoxygenation patterns) or postictal hypoperfusion (deoxygenation patterns) respectively. A new finding of this study is that cortical venous patterns in SWI can be not only focally, but globally attenuated. SWI may thus be considered as an alternative contrast-free MR sequence to identify perfusion changes related to ictal or postictal conditions. PMID:27486662

  11. 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. ...

  12. Febrile Seizures

    MedlinePlus

    ... or prolonged seizures are a risk factor for epilepsy but most children who experience febrile seizures do ... develop the reoccurring seizures that re characteristic of epilepsy. Certain children who have febrile seizures face an ...

  13. Febrile Seizures

    MedlinePlus

    ... febrile seizure does not mean a child has epilepsy, since that disorder is characterized by reoccurring seizures ... outcome but carry an increased risk of developing epilepsy. How common are febrile seizures? Febrile seizures are ...

  14. Absence seizure

    MedlinePlus

    Seizure - petit mal; Seizure - absence; Petit mal seizure; Epilepsy - absence seizure ... Abou-Khalil BW, Gallagher MJ, Macdonald RL. Epilepsies. In: Daroff RB, ... 6th ed. Philadelphia, PA: Elsevier Saunders; 2012:chap ...

  15. Seizures induced by playing music.

    PubMed

    Sutherling, W W; Hershman, L M; Miller, J Q; Lee, S I

    1980-09-01

    A 67-year-old organist and minister with diabetes mellitus had stereotyped focal seizures of the left lower face, jaw, and neck. Attacks occurred spontaneously or were induced when he played a specific hymn on the organ. The seizures were not induced by reading, singing, hearing, or playing the hymn silently. The patient had interictal weakness of the left lower face and left side of the tongue. Focal seizures were recorded on an electroencephalogram (EEG) at the right temporofrontal area. This patient illustrates partial seizures induced by playing music. PMID:6775246

  16. 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. PMID:24766826

  17. Reflex operculoinsular seizures.

    PubMed

    Xiao, Handsun; Tran, Thi Phuoc Yen; Pétrin, Myriam; Boucher, Olivier; Mohamed, Ismail; Bouthillier, Alain; Nguyen, Dang Khoa

    2016-03-01

    Activation of specific cortical territories by certain stimuli is known to trigger focal seizures. We report three cases of well documented operculo-insular reflex seizures, triggered by somatosensory stimuli in two and loud noises in the third. Limited operculoinsular resection resulted in an excellent outcome for all. We discuss these observations in regard to the literature on reflex epilepsy and known functions of the insula. [Published with video sequences online]. PMID:26892245

  18. A unique ictal EEG pattern in a patient with the coexistence of generalized and focal epilepsy.

    PubMed

    Ladino, Lady Diana; Gleadow, Aaron; Téllez-Zenteno, José F

    2015-04-01

    The coexistence of focal and generalized epilepsy is rare. We report on a 17-year-old male with drug-resistant focal epilepsy and idiopathic generalized epilepsy (IGE). He began to experience generalized tonic-clonic seizures (GTCS) at the age of 3 years, with a good response to phenobarbital. At the age of 14 years, he began to experience complex partial seizures (CPS). Video-electroencephalography (video-EEG) telemetry showed the coexistence of right temporal spikes and bursts of generalized spike-wave (GSW). The ictal EEG showed a unique EEG pattern characterized by a 4- to 5-second burst of GSW followed by rhythmic delta activity over the right temporal region. A magnetic resonance image (MRI) showed right hippocampal sclerosis. The patient underwent a right temporal lobectomy that significantly improved his seizure control. He was rendered seizure free of the complex partial seizures and improvement of the GTCS. This case illustrates a very uncommon ictal EEG pattern, and shows that the decision for surgery in patients with focal drug-resistant epilepsy should not be affected by coexistent generalized epilepsy. PMID:24615929

  19. Migrating partial seizures of infancy: expansion of the electroclinical, radiological and pathological disease spectrum

    PubMed Central

    McTague, Amy; Appleton, Richard; Avula, Shivaram; Cross, J. Helen; King, Mary D.; Jacques, Thomas S.; Bhate, Sanjay; Cronin, Anthony; Curran, Andrew; Desurkar, Archana; Farrell, Michael A.; Hughes, Elaine; Jefferson, Rosalind; Lascelles, Karine; Livingston, John; Meyer, Esther; McLellan, Ailsa; Poduri, Annapurna; Scheffer, Ingrid E.; Spinty, Stefan; Kurian, Manju A.

    2013-01-01

    Migrating partial seizures of infancy, also known as epilepsy of infancy with migrating focal seizures, is a rare early infantile epileptic encephalopathy with poor prognosis, presenting with focal seizures in the first year of life. A national surveillance study was undertaken in conjunction with the British Paediatric Neurology Surveillance Unit to further define the clinical, pathological and molecular genetic features of this disorder. Fourteen children with migrating partial seizures of infancy were reported during the 2 year study period (estimated prevalence 0.11 per 100 000 children). The study has revealed that migrating partial seizures of infancy is associated with an expanded spectrum of clinical features (including severe gut dysmotility and a movement disorder) and electrographic features including hypsarrhythmia (associated with infantile spasms) and burst suppression. We also report novel brain imaging findings including delayed myelination with white matter hyperintensity on brain magnetic resonance imaging in one-third of the cohort, and decreased N-acetyl aspartate on magnetic resonance spectroscopy. Putaminal atrophy (on both magnetic resonance imaging and at post-mortem) was evident in one patient. Additional neuropathological findings included bilateral hippocampal gliosis and neuronal loss in two patients who had post-mortem examinations. Within this cohort, we identified two patients with mutations in the newly discovered KCNT1 gene. Comparative genomic hybridization array, SCN1A testing and genetic testing for other currently known early infantile epileptic encephalopathy genes (including PLCB1 and SLC25A22) was non-informative for the rest of the cohort. PMID:23599387

  20. Febrile seizures

    MedlinePlus

    American Academy of Pediatrics, Steering Committee on Quality Improvement and Management, Subcommittee on Febrile Seizures. Febrile seizures: clinical practice guideline for the long-term management of the child with simple febrile seizures. Pediatrics . 2008; ...

  1. [Ecstatic seizures].

    PubMed

    Likhachev, S A; Astapenko, A V; Osos, E L; Zmachynskaya, O L; Gvishch, T G

    2015-01-01

    Ecstatic seizures is a rare manifestation of epilepsy. They were described for the first time by F.M. Dostoevsky. Currently, the description of ecstatic seizures is possible to find in the scientific literature. The description of the own observation of a patient with emotional-affective seizures is presented. A role of the anterior insular cortex in the ecstatic seizures origin is discussed. The similarities between the feelings reported during ecstatic seizures and the feelings experienced under the effect of stimulant addictive drugs are described. The possible reasons of the low frequency of emotional-affective seizures are considered. PMID:26356170

  2. Unraveling the Mystery Behind A Patient with 'Refractory Seizures'.

    PubMed

    Varghese, Mithun Jacob; Lahiri, Anadaroop; Kumar, Vipin; Manuel, Devi A; George, Oommen K

    2016-02-01

    Neurological manifestations such as seizures although rare are well recognized presentations of cardiac arrhythmias. Almost always, such events are primarily generalized in nature leading on to loss of consciousness. Rarely however, cardiac seizures can manifest with focal neurological events. We report a case of a sexagenarian who presented with recurrent focal seizures with secondary generalization, who was misdiagnosed and treated as seizure disorder; only a careful history and focussed investigations helped in realising a precise diagnosis. PMID:27042501

  3. Morphometric MRI alterations and postoperative seizure control in refractory temporal lobe epilepsy.

    PubMed

    Keller, Simon S; Richardson, Mark P; O'Muircheartaigh, Jonathan; Schoene-Bake, Jan-Christoph; Elger, Christian; Weber, Bernd

    2015-05-01

    Refractory mesial temporal lobe epilepsy (mTLE) is a debilitating condition potentially amenable to resective surgery. However, between 40 and 50% patients continue to experience postoperative seizures. The development of imaging prognostic markers of postoperative seizure outcome is a crucial objective for epilepsy research. In the present study, we performed analyses of preoperative cortical thickness and subcortical surface shape on MRI in 115 of patients with mTLE and radiologically defined hippocampal sclerosis being considered for surgery, and 80 healthy controls. Patients with excellent (International League Against Epilepsy outcome (ILAE) I) and suboptimal (ILAE II-VI) postoperative outcomes had a comparable distribution of preoperative atrophy across the cortex, basal ganglia, and amygdala. Conventional volumetry of whole hippocampal and extrahippocampal subcortical structures, and of global gray and white matter, could not differentiate between patient outcome groups. However, surface shape analysis revealed localized atrophy of the thalamus bilaterally and of the posterior/lateral hippocampus contralateral to intended resection in patients with persistent postoperative seizures relative to those rendered seizure free. Data uncorrected for multiple comparisons also revealed focal atrophy of the ipsilateral hippocampus posterior to the margins of resection in patients with persistent seizures. This data indicates that persistent postoperative seizures after temporal lobe surgery are related to localized preoperative shape alterations of the thalamus bilaterally and the hippocampus contralateral to intended resection. Imaging techniques that have the potential to unlock prognostic markers of postoperative outcome in individual patients should focus assessment on a bihemispheric thalamohippocampal network in prospective patients with refractory mTLE being considered for temporal lobe surgery. PMID:25704244

  4. Febrile seizures

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000980.htm Febrile seizures To use the sharing features on this page, please enable JavaScript. A febrile seizure is a convulsion in a child triggered by ...

  5. Acute administration of a small molecule p75NTR ligand does not prevent hippocampal neuron loss nor development of spontaneous seizures after pilocarpine-induced status epilepticus

    PubMed Central

    Grabenstatter, H.L.; Carlsen, J.; Raol, Y.H.; Yang, T.; Hund, D.; Del Angel, Y. Cruz; White, A.M.; Gonzalez, M.I.; Longo, F.M.; Russek, S.J.; Brooks-Kayal, A.R.

    2014-01-01

    Neurotrophins, such as brain-derived neurotrophic factor (BDNF), are initially expressed in a precursor form (e.g., proBDNF) and cleaved to form mature BDNF (mBDNF). Following pilocarpine-induced status epilepticus (SE), increases in neurotrophins regulate a wide variety of cell signaling pathways including pro-survival and cell-death machinery in a receptor-specific manner. ProBDNF preferentially binds to the p75 neurotrophin receptor (p75NTR), while mBDNF is the major ligand of the tropomyosin related kinase receptor (TrkB). To elucidate a potential role of p75NTR in acute stages of epileptogenesis, rats were injected prior to and at onset of SE with LM11A-31, a small molecule ligand that binds to p75NTR to promote survival signaling and inhibit neuronal cell death. Modulation of early p75NTR signaling and its effects on (1) electrographic SE, (2) SE-induced neurodegeneration, and (3) subsequent spontaneous seizures were examined following LM11A-31 administration. Despite an established neuroprotective effect of LM11A-31 in several animal models of neurodegenerative disorders (e.g., Alzheimer’s disease, traumatic brain injury, and spinal cord injury), high-dose LM11A-31 administration prior to and at onset of SE did not reduce the intensity of electrographic SE, prevent SE-induced neuronal cell injury, nor inhibit the progression of epileptogenesis. Further studies are required to understand the role of p75NTR activation during epileptogenesis and in seizure-induced cell injury in the hippocampus among other potential cellular pathologies contributing to the onset of spontaneous seizures. Additional studies utilizing more prolonged treatment with LM11A-31 are required to reach a definite conclusion on its potential neuroprotective role in epilepsy. PMID:24801281

  6. Hypnopompic seizures.

    PubMed

    Awad, Amer M; Lüders, Hans O

    2010-12-01

    The relationship between epilepsy and sleep is complex and bidirectional. Ictal awakening is probably a common and well-described phenomenon. In this small observational study we describe arousal from sleep as the only, or at least main, manifestation of some epileptic seizures. We coin the term "hypnopompic seizures" to describe this entity. Five patients with intractable epilepsy were monitored by continuous video-electroencephalogram. Four of them had left temporal lobe epilepsy and one patient had generalised epilepsy. Hypnopompic seizures accounted for 30-100% of their seizure types captured during monitoring. All the seizures occurred during stage II sleep and were brief. Hypnopompic seizures are extremely subtle and may be underdiagnosed and underreported. Future larger studies are needed to shed some light on this unique entity and its neuropathophysiology. Epileptologists should be aware of this type of seizure and careful review of electroencephalograms during the transition from sleep to arousal is imperative to capture these seizures. Physicians, patients and families also need to be aware of such a subtle manifestation of seizures. Improved awareness of hypnopompic seizures and subtle seizures, in general, help guide accurate and early diagnosis, thorough monitoring and appropriate management. PMID:21030341

  7. Transcriptome profiling of hippocampal CA1 after early-life seizure-induced preconditioning may elucidate new genetic therapies for epilepsy.

    PubMed

    Friedman, L K; Mancuso, J; Patel, A; Kudur, V; Leheste, J R; Iacobas, S; Botta, J; Iacobas, D A; Spray, D C

    2013-07-01

    Injury of the CA1 subregion induced by a single injection of kainic acid (1 × KA) in juvenile animals (P20) is attenuated in animals with two prior sustained neonatal seizures on P6 and P9. To identify gene candidates involved in the spatially protective effects produced by early-life conditioning seizures we profiled and compared the transcriptomes of CA1 subregions from control, 1 × KA- and 3 × KA-treated animals. More genes were regulated following 3 × KA (9.6%) than after 1 × KA (7.1%). Following 1 × KA, genes supporting oxidative stress, growth, development, inflammation and neurotransmission were upregulated (e.g. Cacng1, Nadsyn1, Kcng1, Aven, S100a4, GFAP, Vim, Hrsp12 and Grik1). After 3 × KA, protective genes were differentially over-expressed [e.g. Cat, Gpx7, Gad1, Hspa12A, Foxn1, adenosine A1 receptor, Ca(2+) adaptor and homeostasis proteins, Cacnb4, Atp2b2, anti-apoptotic Bcl-2 gene members, intracellular trafficking protein, Grasp and suppressor of cytokine signaling (Socs3)]. Distinct anti-inflammatory interleukins (ILs) not observed in adult tissues [e.g. IL-6 transducer, IL-23 and IL-33 or their receptors (IL-F2 )] were also over-expressed. Several transcripts were validated by real-time polymerase chain reaction (QPCR) and immunohistochemistry. QPCR showed that casp 6 was increased after 1 × KA but reduced after 3 × KA; the pro-inflammatory gene Cox1 was either upregulated or unchanged after 1 × KA but reduced by ~70% after 3 × KA. Enhanced GFAP immunostaining following 1 × KA was selectively attenuated in the CA1 subregion after 3 × KA. The observed differential transcriptional responses may contribute to early-life seizure-induced pre-conditioning and neuroprotection by reducing glutamate receptor-mediated Ca(2+) permeability of the hippocampus and redirecting inflammatory and apoptotic pathways. These changes could lead to new genetic therapies for epilepsy. PMID:23551718

  8. 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

  9. 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

  10. Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline.

    PubMed

    Cho, Kyung-Ok; Lybrand, Zane R; Ito, Naoki; Brulet, Rebecca; Tafacory, Farrah; Zhang, Ling; Good, Levi; Ure, Kerstin; Kernie, Steven G; Birnbaum, Shari G; Scharfman, Helen E; Eisch, Amelia J; Hsieh, Jenny

    2015-01-01

    Acute seizures after a severe brain insult can often lead to epilepsy and cognitive impairment. Aberrant hippocampal neurogenesis follows the insult but the role of adult-generated neurons in the development of chronic seizures or associated cognitive deficits remains to be determined. Here we show that the ablation of adult neurogenesis before pilocarpine-induced acute seizures in mice leads to a reduction in chronic seizure frequency. We also show that ablation of neurogenesis normalizes epilepsy-associated cognitive deficits. Remarkably, the effect of ablating adult neurogenesis before acute seizures is long lasting as it suppresses chronic seizure frequency for nearly 1 year. These findings establish a key role of neurogenesis in chronic seizure development and associated memory impairment and suggest that targeting aberrant hippocampal neurogenesis may reduce recurrent seizures and restore cognitive function following a pro-epileptic brain insult. PMID:25808087

  11. Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline

    PubMed Central

    Cho, Kyung-Ok; Lybrand, Zane R.; Ito, Naoki; Brulet, Rebecca; Tafacory, Farrah; Zhang, Ling; Good, Levi; Ure, Kerstin; Kernie, Steven G.; Birnbaum, Shari G.; Scharfman, Helen E.; Eisch, Amelia J.; Hsieh, Jenny

    2015-01-01

    Acute seizures after a severe brain insult can often lead to epilepsy and cognitive impairment. Aberrant hippocampal neurogenesis follows the insult but the role of adult-generated neurons in the development of chronic seizures or associated cognitive deficits remains to be determined. Here we show that the ablation of adult neurogenesis before pilocarpine-induced acute seizures in mice leads to a reduction in chronic seizure frequency. We also show that ablation of neurogenesis normalizes epilepsy-associated cognitive deficits. Remarkably, the effect of ablating adult neurogenesis before acute seizures is long lasting as it suppresses chronic seizure frequency for nearly 1 year. These findings establish a key role of neurogenesis in chronic seizure development and associated memory impairment and suggest that targeting aberrant hippocampal neurogenesis may reduce recurrent seizures and restore cognitive function following a pro-epileptic brain insult. PMID:25808087

  12. Hippocampal Sclerosis: Causes and Prevention.

    PubMed

    Walker, Matthew Charles

    2015-06-01

    Hippocampal sclerosis is the commonest cause of drug-resistant epilepsy in adults, and is associated with alterations to structures and networks beyond the hippocampus.In addition to being a cause of epilepsy, the hippocampus is vulnerable to damage from seizure activity. In particular, prolonged seizures (status epilepticus) can result in hippocampal sclerosis. The hippocampus is also vulnerable to other insults including traumatic brain injury, and inflammation. Hippocampal sclerosis can occur in association with other brain lesions; the prevailing view is that it is probably a secondary consequence. In such instances, successful surgical treatment usually involves the resection of both the lesion and the involved hippocampus. Experimental data have pointed to numerous neuroprotective strategies to prevent hippocampal sclerosis. Initial neuroprotective strategies aimed at glutamate receptors may be effective, but later, metabolic pathways, apoptosis, reactive oxygen species, and inflammation are involved, perhaps necessitating the use of interventions aimed at multiple targets. Some of the therapies that we use to treat status epilepticus may neuroprotect. However, prevention of neuronal death does not necessarily prevent the later development of epilepsy or cognitive deficits. Perhaps, the most important intervention is the early, aggressive treatment of seizure activity, and the prevention of prolonged seizures. PMID:26060898

  13. Galactosemia and phantom absence seizures.

    PubMed

    Aydin-Özemir, Zeynep; Tektürk, Pınar; Uyguner, Zehra Oya; Baykan, Betül

    2014-01-01

    Generalized and focal seizures can rarely be seen in galactosemia patients, but absence seizures were not reported previously. An 18-year-old male was diagnosed as galactosemia at the age of 8 months. No family history of epilepsy was present. His absence seizures realized at the age of 9 years. Generalized 3-4 Hz spike-wave discharges were identified in his electroencephalography. Homozygous mutation at exon 6 c. 563A > G was identified. The electroencephalogram of his sibling was unremarkable. Our aim was to present the long-term follow-up of a patient diagnosed with galactosemia, who had phantom absence seizures and typical 3-4 Hz spike-wave discharges in his electroencephalogram to draw attention to this rare association. PMID:25624930

  14. 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. PMID:26621617

  15. 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…

  16. 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

  17. Generalized tonic-clonic seizure

    MedlinePlus

    ... Seizure - grand mal; Grand mal seizure; Seizure - generalized; Epilepsy - generalized seizure ... occur as part of a repeated, chronic illness (epilepsy). Some seizures are due to psychological problems (psychogenic).

  18. Visual reflex seizures induced by complex stimuli.

    PubMed

    Zifkin, Benjamin G; Inoue, Yushi

    2004-01-01

    Visual reflex seizures induced by complex stimuli may be triggered by patterned and flashing displays that are now ubiquitous. The seizures may be clinically generalized, but unilateral and bilateral myoclonic attacks also may be triggered, especially in patients with juvenile myoclonic epilepsy, and recently, clearly focal reflex occipital lobe seizures have been described. Some seizure-triggering properties of video displays can be identified, such as perceived brightness, pattern, flicker frequency, and color. Knowledge of these is useful in planning individual treatment and in designing regulations for screen content of television broadcasts or for other video displays. Some subjects will also be sensitive to cognitive or action-programming activation, especially when playing video games, and this can increase the chance of seizure triggering. Nonspecific factors such as sleep deprivation, prolonged exposure, and drug or alcohol use also may play a role in reflex seizure occurrence. PMID:14706042

  19. Changes in hormone and lipid levels in male patients with focal seizures when switched from carbamazepine to lacosamide as adjunctive treatment to levetiracetam: A small phase IIIb, prospective, multicenter, open-label trial.

    PubMed

    Elger, Christian E; Rademacher, Michael; Brandt, Christian; Elmoufti, Sami; Dedeken, Peter; Eckhardt, Klaus; Tennigkeit, Frank; De Backer, Marc

    2016-09-01

    Treatment with enzyme-inducing antiepileptic drugs (AEDs) such as carbamazepine (CBZ) can lead to changes in reproductive, endocrine, and lipid parameters, resulting in clinical symptoms for some patients. Previous studies indicate that these changes can be reversed by switching to a nonenzyme-inducing AED. Lacosamide is a newer-generation AED, not known to induce or strongly inhibit cytochrome P450 (CYP450) enzymes. In this phase IIIb, prospective, multicenter, open-label, single-arm trial (NCT01375374), the serum concentrations of CYP-related reproductive hormones, thyroid hormones, and lipids were assessed in otherwise healthy male patients with focal seizures (N=11), before and after a switch from CBZ (600-1200mg/day at baseline) to lacosamide (target dose: 400mg/day by the end of titration) as adjunctive treatment to the nonenzyme-inducing AED levetiracetam (LEV, stable dosage of >1000mg/day throughout). Cross titration took place over 4weeks, followed by an 8-week maintenance period. Serum measurements were conducted at baseline and at the end of maintenance. The median serum sex-hormone-binding globulin (SHBG) concentration was towards the higher end of the normal range at baseline and decreased following the switch (61.7 to 47.5nmol/L, N=10, p=0.027 by Wilcoxon signed-rank test). Free androgen index (100×testosterone/SHBG) and free thyroxine serum concentration increased (25.4 to 36.4 and 13.0 to 14.9pmol/L, respectively, both N=10 and p=0.002). At baseline, the median progesterone serum concentration was below the normal range (0.7nmol/L), whereas median cholesterol and low-density lipoprotein concentrations were above the normal range (5.5 and 3.6mmol/L, respectively). By the end of maintenance, all measured parameters were within the normal range. The safety and tolerability profile of lacosamide was consistent with that observed in previous studies. Furthermore, antiseizure efficacy appeared to be maintained, suggesting that deinduction of CYP enzymes

  20. Frontal lobe epilepsy with atypical seizure semiology resembling shuddering attacks or wet dog shake seizures.

    PubMed

    Jahodova, Alena; Krsek, Pavel; Komarek, Vladimir; Kudr, Martin; Kyncl, Martin; Zamecnik, Josef; Tichy, Michal

    2012-03-01

    We report a girl with a drug-resistant frontal lobe epilepsy caused by focal cortical dysplasia, who exhibited uncommon seizures. The seizures consisted of shoulder or whole body shuddering after a short psychic aura and face grimacing. Consciousness was fully preserved. The seizures resembled "wet dog shake" seizures described in rat models of epilepsy or shuddering attacks in infants. EEG findings were inconclusive, however, MRI showed a clear dysplastic lesion in the right frontal mesial and polar structures. The patient underwent an extended lesionectomy guided by neuronavigation and intraoperative electrocorticography. Focal cortical dysplasia type Ib was histologically confirmed and the patient has been seizure-free for the three years following resection. [Published with video sequences]. PMID:22425715

  1. Controlling Seizures

    ERIC Educational Resources Information Center

    Henderson, Nancy

    2008-01-01

    This article describes how an implantable device could greatly improve the quality of life for people with epilepsy. Gabe Anderson was diagnosed with bilateral heterotopia, a congenital condition that can lead to the onset of complex partial seizures stemming from both hemispheres of the brain. In early 2004, Gabe became one of the first 35…

  2. Evaluation of Bax and Bcl-2 Proteins Expression in the Rat Hippocampus due to Childhood Febrile Seizure

    PubMed Central

    SAEEDI BORUJENI, Mohammad Javad; HAMI, Javad; HAGHIR, Hossein; RASTIN, Maryam; SAZEGAR, Ghasem

    2016-01-01

    Objective Simple Febrile Seizure (SFS) is the most common seizure disorder in childhood, and is frequently described as inoffensive disorder. Nevertheless, there is evidence suggesting the association between neonatal febrile seizures and hippocampal abnormalities in adulthood. This study was conducted at evaluating the hippocampal expression of pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins following SFS induction in rat neonates. Materials & Methods Febrile seizure was modeled by hyperthermia-induced seizure in 22-dayold male rats by a hot water bath. The animals were divided into two groups based on the presence or absence of seizure behaviors: Hyperthermia without seizure (n=10) and hyperthermia with seizure (n=10). To control the effects of environmental stress a sham-control group was also added (n=10). The rats’ hippocampi were dissected 2 or 15 days after hyperthermia. The expression of Bax and Bcl-2 proteins were measured using Western Blotting technique. Results The hippocampal expression of Bcl-2 protein was significantly lower in the hyperthermia with seizure animals than that of the sham-control and hyperthermia without seizure groups. The expression of pro-apoptotic Bax protein also significantly increased in the hippocampus of hyperthermia with seizure group rats compared to the sham-control and hyperthermia without seizure animals. Conclusion The simple febrile seizure markedly disturbed the hippocampal expression of both Bcl2 and Bax proteins, resulting in apoptosis promotion in hippocampi of juvenile rats, which were measurable for at least 15 days. PMID:27057189

  3. L-Theanine intake increases threshold for limbic seizures but decreases threshold for generalized seizures.

    PubMed

    Schallier, Anneleen; Vermoesen, Katia; Loyens, Ellen; Van Liefferinge, Joeri; Michotte, Yvette; Smolders, Ilse; Massie, Ann

    2013-03-01

    L-Theanine, an ethylamide derivate of glutamate found in abundance in green tea, has been shown to exert beneficial actions in animal models for several neurological disorders. We here investigated for the first time the effect of L-theanine intake on seizure susceptibility using acute pilocarpine and pentylenetetrazol (PTZ) mouse models for studying, respectively, limbic seizures or primarily generalized seizures. Moreover, we studied the effect of l-theanine intake on extracellular hippocampal and cortical glutamate and gamma-aminobutyric acid (GABA) levels, using in vivo microdialysis. Feeding mice with a 4% L-theanine solution significantly decreased their susceptibility to pilocarpine-induced seizures whereas susceptibility to PTZ-induced seizures was increased. The latter effect was linked to decreased extracellular GABA concentrations in frontal cortex. PMID:23324588

  4. Posterior reversible encephalopathy syndrome (PRES): electroencephalographic findings and seizure patterns.

    PubMed

    Kastrup, Oliver; Gerwig, Markus; Frings, Markus; Diener, Hans-Christoph

    2012-07-01

    To better describe seizure type, frequency, and electroencephalographic (EEG) findings in posterior reversible encephalopathy syndrome (PRES) and correlate these data with clinical and magnetic resonance imaging (MRI) data, we retrospectively assessed medical charts and EEG studies of patients with PRES treated between 2004 and 2011. Data collected included patients' underlying pathology, lesion distribution by MRI, seizure type and frequency, EEG pathologic background activity, focal pathology, and epileptogenic activity. Thirty-eight of 49 adults with PRES suffered from seizures; 17 underwent EEG and were included in the analysis. Perpetuating factors were similar to those reported in the literature. In 15 of 17 patients, MRI showed widespread involvement rather than purely occipital lesions. Nine patients had subcortical and cortical involvement. Seizures were single short grand mal (GM) in 11, serial GM in 2, recurrent GM in 2, and additional focal seizures in 2. No seizures were noted beyond the first day. After discontinuation of antiepileptic medication, no patients experienced seizure recurrence during 6-month follow-up. EEG showed diffuse theta/delta slowing in 13 patients and epileptogenic activity with focal sharp-wave and periodic lateralizing epileptiform discharges in 2 patients. Seizures in PRES are most commonly single GM and are usually of limited duration. EEG shows variable theta/delta slowing. Focal EEG pathology is seen in patients with focal seizures. Seizures occur early after disease onset and terminate spontaneously or under therapy during the first 24 h. Seizure recurrence beyond 24 h and chronic epilepsy were not seen. Seizures in PRES are frequent but appear to be uncomplicated and do not herald worse prognosis. EEG is helpful in evaluating the degree of encephalopathy and monitoring epileptic activity. Long-term antiepileptic medication does not appear to be warranted. PMID:22189837

  5. A practical approach to uncomplicated seizures in children.

    PubMed

    McAbee, G N; Wark, J E

    2000-09-01

    Uncomplicated seizures and epilepsy are common in infants and children. Family physicians should be aware of certain epilepsy syndromes that occur in children, such as febrile seizures, benign focal epilepsy of childhood, complex partial epilepsy, juvenile myoclonic epilepsy and video game-related epilepsy. Not all uncomplicated childhood seizures require neuroimaging or treatment. Febrile seizures, rolandic seizures and video game-related seizures are childhood epileptic syndromes that are typically not associated with brain structural lesions on computed tomography or magnetic resonance imaging, and are often not treated with anticonvulsant drugs. Juvenile myoclonic epilepsy does not require neuroimaging but does require treatment because of a high rate of recurrent seizures. Complex partial epilepsy often requires both neuroimaging and treatment. Although seizures are diagnosed primarily on clinical grounds, all children with a possible seizure (except febrile seizures) should have an electroencephalogram. Interictal EEGs may be normal. Computed tomography has demonstrated abnormalities in 7 to 19 percent of children with new-onset seizures. The yield of magnetic resonance imaging for specific childhood seizure types is not known, but it is the preferred modality of neuroimaging for many clinical presentations. Most children's seizures treated with anticonvulsants are controlled by the first drug selected. The value of "therapeutic' serum drug levels is questionable in the management of uncomplicated childhood seizures. PMID:10997534

  6. Febrile seizures

    PubMed Central

    2014-01-01

    Febrile seizure (FS) is the most common seizure disorder of childhood, and occurs in an age-related manner. FS are classified into simple and complex. FS has a multifactorial inheritance, suggesting that both genetic and environmental factors are causative. Various animal models have elucidated the pathophysiological mechanisms of FS. Risk factors for a first FS are a family history of the disorder and a developmental delay. Risk factors for recurrent FS are a family history, age below 18 months at seizure onset, maximum temperature, and duration of fever. Risk factors for subsequent development of epilepsy are neurodevelopmental abnormality and complex FS. Clinicians evaluating children after a simple FS should concentrate on identifying the cause of the child's fever. Meningitis should be considered in the differential diagnosis for any febrile child. A simple FS does not usually require further evaluation such as ordering electroencephalography, neuroimaging, or other studies. Treatment is acute rescue therapy for prolonged FS. Antipyretics are not proven to reduce the recurrence risk for FS. Some evidence shows that both intermittent therapy with oral/rectal diazepam and continuous prophylaxis with oral phenobarbital or valproate are effective in reducing the risk of recurrence, but there is no evidence that these medications reduce the risk of subsequent epilepsy. Vaccine-induced FS is a rare event that does not lead to deleterious outcomes, but could affect patient and physician attitudes toward the safety of vaccination. PMID:25324864

  7. Why Are Seizures Rare in Rapid Eye Movement Sleep? Review of the Frequency of Seizures in Different Sleep Stages

    PubMed Central

    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. PMID:23853720

  8. Seizure Disorders in Pregnancy

    MedlinePlus

    ... Seizures that cause a loss of consciousness and violent, jerking movements, called grand mal seizures , are especially ... of seizure that causes loss of consciousness and violent, jerking movements. Intrauterine Device: A small device that ...

  9. Hyperactive mTOR signals in the proopiomelanocortin-expressing hippocampal neurons cause age-dependent epilepsy and premature death in mice.

    PubMed

    Matsushita, Yuki; Sakai, Yasunari; Shimmura, Mitsunori; Shigeto, Hiroshi; Nishio, Miki; Akamine, Satoshi; Sanefuji, Masafumi; Ishizaki, Yoshito; Torisu, Hiroyuki; Nakabeppu, Yusaku; Suzuki, Akira; Takada, Hidetoshi; Hara, Toshiro

    2016-01-01

    Epilepsy is a frequent comorbidity in patients with focal cortical dysplasia (FCD). Recent studies utilizing massive sequencing data identified subsets of genes that are associated with epilepsy and FCD. AKT and mTOR-related signals have been recently implicated in the pathogenic processes of epilepsy and FCD. To clarify the functional roles of the AKT-mTOR pathway in the hippocampal neurons, we generated conditional knockout mice harboring the deletion of Pten (Pten-cKO) in Proopiomelanocortin-expressing neurons. The Pten-cKO mice developed normally until 8 weeks of age, then presented generalized seizures at 8-10 weeks of age. Video-monitored electroencephalograms detected paroxysmal discharges emerging from the cerebral cortex and hippocampus. These mice showed progressive hypertrophy of the dentate gyrus (DG) with increased expressions of excitatory synaptic markers (Psd95, Shank3 and Homer). In contrast, the expression of inhibitory neurons (Gad67) was decreased at 6-8 weeks of age. Immunofluorescence studies revealed the abnormal sprouting of mossy fibers in the DG of the Pten-cKO mice prior to the onset of seizures. The treatment of these mice with an mTOR inhibitor rapamycin successfully prevented the development of seizures and reversed these molecular phenotypes. These data indicate that the mTOR pathway regulates hippocampal excitability in the postnatal brain. PMID:26961412

  10. Hyperactive mTOR signals in the proopiomelanocortin-expressing hippocampal neurons cause age-dependent epilepsy and premature death in mice

    PubMed Central

    Matsushita, Yuki; Sakai, Yasunari; Shimmura, Mitsunori; Shigeto, Hiroshi; Nishio, Miki; Akamine, Satoshi; Sanefuji, Masafumi; Ishizaki, Yoshito; Torisu, Hiroyuki; Nakabeppu, Yusaku; Suzuki, Akira; Takada, Hidetoshi; Hara, Toshiro

    2016-01-01

    Epilepsy is a frequent comorbidity in patients with focal cortical dysplasia (FCD). Recent studies utilizing massive sequencing data identified subsets of genes that are associated with epilepsy and FCD. AKT and mTOR-related signals have been recently implicated in the pathogenic processes of epilepsy and FCD. To clarify the functional roles of the AKT-mTOR pathway in the hippocampal neurons, we generated conditional knockout mice harboring the deletion of Pten (Pten-cKO) in Proopiomelanocortin-expressing neurons. The Pten-cKO mice developed normally until 8 weeks of age, then presented generalized seizures at 8–10 weeks of age. Video-monitored electroencephalograms detected paroxysmal discharges emerging from the cerebral cortex and hippocampus. These mice showed progressive hypertrophy of the dentate gyrus (DG) with increased expressions of excitatory synaptic markers (Psd95, Shank3 and Homer). In contrast, the expression of inhibitory neurons (Gad67) was decreased at 6–8 weeks of age. Immunofluorescence studies revealed the abnormal sprouting of mossy fibers in the DG of the Pten-cKO mice prior to the onset of seizures. The treatment of these mice with an mTOR inhibitor rapamycin successfully prevented the development of seizures and reversed these molecular phenotypes. These data indicate that the mTOR pathway regulates hippocampal excitability in the postnatal brain. PMID:26961412

  11. 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…

  12. DC potentials of temporal lobe seizures in the monkey.

    PubMed

    Mayanagi, Y; Walker, A E

    1975-07-01

    In 8 monkeys, made epileptic by alum or penicillin injection into temporal lobe structures, 40 seizures were studied by both DC cortical potential and subcortical EEG recordings. Eighteen seizures of lateral temporal origin had an abrupt negative DC potential shift of 0.5 to 2.0 mV in and around the focus. The frontal, parietal and occipital cortices did not develop DC potential changes, perhaps due to the limited propagation of the neocortical seizures. Twenty-two seizures of medial temporal origin showed a negative shift of the anterior, inferior or lateral temporal cortex in 85% of seizures. The other 15% had a positive or no shift. In hippocampal seizures, a positive displacement was sometimes seen prior to the main negative shift in the lateral temporal cortex. The remote cortex developed only a minimal positive shift in 30% of the mediotemporal seizures. A marked negative shift in the frontocentral cortex was the first sign of impending generalization, which may result from a series of chain reactions with seizure propagation, involving more and more structures of the brain. Registration of DC potentials in temporal lobe seizures may give insight into the nature of abnormal EEG activities and to some extent into the origin of seizures. PMID:51061

  13. Assimilating Seizure Dynamics

    PubMed Central

    Ullah, Ghanim; Schiff, Steven J.

    2010-01-01

    Observability of a dynamical system requires an understanding of its state—the collective values of its variables. However, existing techniques are too limited to measure all but a small fraction of the physical variables and parameters of neuronal networks. We constructed models of the biophysical properties of neuronal membrane, synaptic, and microenvironment dynamics, and incorporated them into a model-based predictor-controller framework from modern control theory. We demonstrate that it is now possible to meaningfully estimate the dynamics of small neuronal networks using as few as a single measured variable. Specifically, we assimilate noisy membrane potential measurements from individual hippocampal neurons to reconstruct the dynamics of networks of these cells, their extracellular microenvironment, and the activities of different neuronal types during seizures. We use reconstruction to account for unmeasured parts of the neuronal system, relating micro-domain metabolic processes to cellular excitability, and validate the reconstruction of cellular dynamical interactions against actual measurements. Data assimilation, the fusing of measurement with computational models, has significant potential to improve the way we observe and understand brain dynamics. PMID:20463875

  14. Assimilating seizure dynamics.

    PubMed

    Ullah, Ghanim; Schiff, Steven J

    2010-05-01

    Observability of a dynamical system requires an understanding of its state-the collective values of its variables. However, existing techniques are too limited to measure all but a small fraction of the physical variables and parameters of neuronal networks. We constructed models of the biophysical properties of neuronal membrane, synaptic, and microenvironment dynamics, and incorporated them into a model-based predictor-controller framework from modern control theory. We demonstrate that it is now possible to meaningfully estimate the dynamics of small neuronal networks using as few as a single measured variable. Specifically, we assimilate noisy membrane potential measurements from individual hippocampal neurons to reconstruct the dynamics of networks of these cells, their extracellular microenvironment, and the activities of different neuronal types during seizures. We use reconstruction to account for unmeasured parts of the neuronal system, relating micro-domain metabolic processes to cellular excitability, and validate the reconstruction of cellular dynamical interactions against actual measurements. Data assimilation, the fusing of measurement with computational models, has significant potential to improve the way we observe and understand brain dynamics. PMID:20463875

  15. Regulating hippocampal hyperexcitability through GABAB Receptors

    PubMed Central

    Lang, Min; Moradi‐Chameh, Homeira; Zahid, Tariq; Gane, Jonathan; Wu, Chiping; Valiante, Taufik; Zhang, Liang

    2014-01-01

    Abstract Disturbances of GABAergic inhibition are a major cause of epileptic seizures. GABA exerts its actions via ionotropic GABAA receptors and metabotropic G protein‐coupled GABAB receptors. Malfunction of GABAA inhibition has long been recognized in seizure genesis but the role of GABAB receptors in controlling seizure activity is still not well understood. Here, we examined the anticonvulsive, or inhibitory effects, of GABAB receptors in a mouse model of hippocampal kindling as well as mouse hippocampal slices through the use of GS 39783, a positive allosteric GABAB receptor modulator, and CGP 55845, a selective GABAB receptor antagonist. When administered via intraperitoneal injections in kindled mice, GS 39783 (5 mg/kg) did not attenuate hippocampal EEG discharges, but did reduce aberrant hippocampal spikes, whereas CGP 55845 (10 mg/kg) prolonged hippocampal discharges and increased spike incidences. When examined in hippocampal slices, neither GS 39783 at 5 μmol/L nor the GABAB receptor agonist baclofen at 0.1 μmol/L alone significantly altered repetitive excitatory field potentials, but GS 39783 and baclofen together reversibly abolished these field potentials. In contrast, CGP 55845 at 1 μmol/L facilitated induction and incidence of these field potentials. In addition, CGP 55845 attenuated the paired pulse depression of CA3 population spikes and increased the frequency of EPSCs in individual CA3 pyramidal neurons. Collectively, these data suggest that GABABB receptors regulate hippocampal hyperexcitability by inhibiting CA3 glutamatergic synapses. We postulate that positive allosteric modulation of GABAB receptors may be effective in reducing seizure‐related hyperexcitability. PMID:24771688

  16. Clinical analysis of leucine-rich glioma inactivated-1 protein antibody associated with limbic encephalitis onset with seizures

    PubMed Central

    Li, Zhimei; Cui, Tao; Shi, Weixiong; Wang, Qun

    2016-01-01

    Abstract We summarized the clinical characteristics of patients presenting with seizures and limbic encephalitis (LE) associated with leucine-rich glioma inactivated-1 protein antibody (LGI1) in order help recognize and treat this condition at its onset. We analyzed clinical, video electroencephalogram (VEEG), magnetic resonance imaging (MRI), and laboratory data of 10 patients who presented with LGI1-LE and followed up their outcomes from 2 to 16 (9.4 ± 4.2) months. All patients presented with seizures onset, including faciobrachial dystonic seizure (FBDS), partial seizure (PS), and generalized tonic-clonic seizure (GTCS). Four patients (Cases 3, 5, 7, and 8) had mild cognitive deficits. Interictal VEEG showed normal patterns, focal slowing, or sharp waves in the temporal or frontotemporal lobes. Ictal VEEG of Cases 4, 5, and 7 showed diffuse voltage depression preceding FBDS, a left frontal/temporal origin, and a bilateral temporal origin, respectively. Ictal foci could not be localized in other cases. MRI scan revealed T2/fluid-attenuated inversion recovery (FLAIR) hyperintensity and evidence of edema in the right medial temporal lobe in Case 3, left hippocampal atrophy in Case 5, hyperintensities in the bilateral medial temporal lobes in Case 7, and hyperintensities in the basal ganglia and frontal cortex in Case 10. All 10 serum samples were positive for LGI1 antibody, but it was only detected in the cerebrospinal fluid (CSF) of 7 patients. Five patients (Cases 2, 4, 6, 7, and 8) presented with hyponatremia. One patient (Case 2) was diagnosed with small cell lung cancer. While responses to antiepileptic drugs (AEDs) were poor, most patients (except Case 2) responded favorably to immunotherapy. LGI1-LE may initially manifest with various types of seizures, particularly FBDS and complex partial seizures (CPS) of mesial temporal origin, and slowly progressive cognitive involvement. Clinical follow-up, VEEG monitoring, and MRI scan are helpful in early

  17. Experimental febrile seizures impair interastrocytic gap junction coupling in juvenile mice.

    PubMed

    Khan, Dilaware; Dupper, Alexander; Deshpande, Tushar; Graan, Pierre N E De; Steinhäuser, Christian; Bedner, Peter

    2016-09-01

    Prolonged and focal febrile seizures (FSs) have been associated with the development of temporal lobe epilepsy (TLE), although the underlying mechanism and the contribution of predisposing risk factors are still poorly understood. Using a kainate model of TLE, we previously provided strong evidence that interruption of astrocyte gap junction-mediated intercellular communication represents a crucial event in epileptogenesis. To elucidate this aspect further, we induced seizures in immature mice by hyperthermia (HT) to study the consequences of FSs on the hippocampal astrocytic network. Changes in interastrocytic coupling were assessed by tracer diffusion studies in acute slices from mice 5 days after experimental FS induction. The results reveal that HT-induced FSs cause a pronounced reduction of astrocyte gap junctional coupling in the hippocampus by more than 50%. Western blot analysis indicated that reduced connexin43 protein expression and/or changes in the phosphorylation status account for this astrocyte dysfunction. Remarkably, uncoupling occurred in the absence of neuronal death and reactive gliosis. These data provide a mechanistic link between FSs and the subsequent development of TLE and further strengthen the emerging view that astrocytes have a central role in the pathogenesis of this disorder. © 2016 Wiley Periodicals, Inc. PMID:26931373

  18. Modeling early-onset post-ischemic seizures in aging mice

    PubMed Central

    Wu, Chiping; Wang, Justin; Peng, Jessie; Patel, Nisarg; Huang, Yayi; Gao, Xiaoxing; Aljarallah, Salman; Eubanks, James H; McDonald, Robert; Zhang, Liang

    2016-01-01

    Stroke is the leading cause of seizures and epilepsy in the aged population, with post-stroke seizures being a poor prognostic factor. The pathological processes underlying post-stroke seizures are not well understood and studies of these seizures in aging/aged animals remain scarce. Therefore, our primary objective was to model post-stroke seizures in aging mice (C57 black strain, 16–20 month-old), with a focus on early-onset, convulsive seizures that occur within 24-hours of brain ischemia. We utilized a middle cerebral artery occlusion model and examined seizure activity and brain injury using combined behavioral and electroencephalographic monitoring and histological assessments. Aging mice exhibited vigorous convulsive seizures within hours of the middle cerebral artery occlusion. These seizures manifested with jumping, rapid running, barrel-rolling and/or falling all in the absence of hippocampal-cortical electrographic discharges. Seizure development was closely associated with severe brain injury and acute mortality. Anticonvulsive treatments after seizure occurrence offered temporary seizure control but failed to improve animal survival. A separate cohort of adult mice (6–8 months-old) exhibited analogous early-onset convulsive seizures following the middle cerebral artery occlusion but had better survival outcomes following anticonvulsive treatment. Collectively, our data suggest that early-onset convulsive seizures are a result of severe brain ischemia in aging animals. PMID:25943585

  19. 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. PMID:26875662

  20. 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. PMID:26575850

  1. Search and Seizure.

    ERIC Educational Resources Information Center

    Murray, Kenneth T.

    This paper examines the practice of search and seizure from a legal perspective. All issues concerning lawful or unlawful search and seizure, whether in a public school or otherwise, are predicated upon the Fourth Amendment to the United States Constitution. The terms "search,""seizure,""probable cause,""reasonable suspicion," and "exclusionary…

  2. Mapping preictal networks preceding childhood absence seizures using magnetoencephalography.

    PubMed

    Jacobs-Brichford, Eliza; Horn, Paul S; Tenney, Jeffrey R

    2014-10-01

    The electrographic hallmark of childhood absence seizures is 3 Hz generalized spike and wave discharges; however, there is likely a focal thalamic or cortical onset that cannot be detected using scalp electroencephalography (EEG). The purpose of this study was to study the earliest preictal changes in children with absence epilepsy. In this report, magnetoencephalography recordings of 44 absence seizures recorded from 12 children with drug-naïve childhood absence seizures were used to perform time frequency analysis and source localization prior to the onset of the seizures. Evidence of preictal magnetoencephalography frequency changes were detected a mean of 694 ms before the initial spike on the EEG. A consistent pattern of focal sources was present in the frontal cortex and thalamus during this preictal period, but source localization occurred synchronously so that independent activity between the 2 structures could not be distinguished. PMID:24532809

  3. The behavioral treatment of epilepsy generation and inhibition of seizures.

    PubMed

    Fenwick, P

    1994-02-01

    These studies provide abundant evidence of the close interrelation between seizure activity and behavior. They reaffirm the point that epileptic seizures do not occur in a behavioral vacuum and strengthen the theoretical framework for behavioral treatment of epilepsy patients. As our understanding of the epileptic focus and its connections to surrounding cerebral systems increases, the concept that seizure control is significantly influenced by altering behavior of the patient becomes more comprehensible. Epileptic seizures should not be thought of as arising randomly. They occur in focal seizures when the pools of neurons surrounding the epilepsy focus are sufficiently excited for seizure activity to spread. Generalized seizures occur when the level of cortical excitability, or corticoreticular excitation, has reached a point at which thalamic recruiting volleys generalize and start to spread. In the partial epilepsies, a detailed clinical history should be taken as to the nature and characteristics of the aura and the form that seizure generalization or spread may take. Charting events surrounding the time of the seizure as described below are the engine which drives the creation of a countermeasure and its application to stopping seizures. They are the heart of a behavioral program and skill in interpreting the data will be repaid by the finding of the appropriate countermeasures for seizure reduction. This information will define those aspects of the patient's psychic life or behavior that will both trigger and inhibit seizure activity. Discussing this information with the patient will help him or her to understand that their seizures are not necessarily random events, but are intimately related to feelings, actions, and thoughts. A complete treatment of epilepsy involves not just medication, but includes teaching the patient about their brain and its functioning, and how they can use their feelings, thinking, and behavior in the control of their epilepsy. PMID

  4. 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

  5. Does aspirin use make it harder to collect seizures during elective video-EEG telemetry?

    PubMed

    Godfred, Rachel M; Parikh, Mihir S; Haltiner, Alan M; Caylor, Lisa M; Sepkuty, Jehuda P; Doherty, Michael J

    2013-04-01

    Aspirin has shown promise as an anticonvulsant drug in animal models. Whether aspirin alters seizure frequency in humans remains unstudied. We retrospectively looked at adults with focal onset epilepsy who took aspirin daily while undergoing elective video-EEG monitoring and compared them with similar age- and sex-matched controls to see if seizure frequencies were different between those two populations. Significantly fewer seizures were seen on day two of monitoring for patients on aspirin therapies. Higher aspirin doses were correlated with fewer seizures collected during the monitoring stay. Further prospective study is needed to determine whether aspirin affects more robust seizure control. PMID:23399946

  6. Neurocysticercosis presenting as focal hydrocephalus

    PubMed Central

    Malik, Azharuddin Mohammed; Shamim, Md Dilawez; Ahmad, Mehtab; Abdali, Nasar

    2014-01-01

    A 40-year-old man presented with a 2-month history of headache, nausea and vomiting, with generalised seizures for the past 15 days. On examination he had bilateral papilloedema, visual acuity was 6/6 in both eyes but perimetry showed right homonymous inferior quadrantanopia. His MRI showed numerous small cystic lesions with eccentric nodules, diffusely distributed in bilateral cerebral and cerebellar hemispheres. There was also focal hydrocephalus involving occipital and temporal horns of the left lateral ventricle leading to its selective dilation. Stool examination showed ova of Taenia solium. He was treated with albendazole, prednisone and sustained release sodium valproate for 1 month. His headache resolved and he is free of seizures. Repeat perimetry at 1 month also showed resolution of visual field defect. PMID:24962486

  7. Nitric Oxide Regulates Neurogenesis in the Hippocampus following Seizures

    PubMed Central

    Carreira, Bruno P.; Santos, Daniela F.; Santos, Ana I.; Carvalho, Caetana M.; Araújo, Inês M.

    2015-01-01

    Hippocampal neurogenesis is changed by brain injury. When neuroinflammation accompanies injury, activation of resident microglial cells promotes the release of inflammatory cytokines and reactive oxygen/nitrogen species like nitric oxide (NO). In these conditions, NO promotes proliferation of neural stem cells (NSC) in the hippocampus. However, little is known about the role of NO in the survival and differentiation of newborn cells in the injured dentate gyrus. Here we investigated the role of NO following seizures in the regulation of proliferation, migration, differentiation, and survival of NSC in the hippocampus using the kainic acid (KA) induced seizure mouse model. We show that NO increased the proliferation of NSC and the number of neuroblasts following seizures but was detrimental to the survival of newborn neurons. NO was also required for the maintenance of long-term neuroinflammation. Taken together, our data show that NO positively contributes to the initial stages of neurogenesis following seizures but compromises survival of newborn neurons. PMID:26587180

  8. Clinically silent seizures in a neonate with tuberous sclerosis.

    PubMed

    Ikeno, Mitsuru; Okumura, Akihisa; Abe, Shinpei; Igarashi, Ayuko; Hisata, Ken; Shoji, Hiromichi; Shimizu, Toshiaki

    2016-01-01

    Although seizures during infancy in patients with tuberous sclerosis complex are common, seizures in neonates are infrequent. Here, we report the clinical course and electroencephalography (EEG) findings of a neonate with tuberous sclerosis complex associated with clinically silent seizures. The patient was a girl in whom cardiac tumors were detected on fetal ultrasonography. Brain magnetic resonance imaging during the neonatal period showed subependymal and cortical tubers. Routine EEG indicated unexpected ictal changes with no noticeable clinical symptoms. Ictal EEG was associated with a subtle increase in heart rate and a brief increase in chin electromyogram. These changes were difficult to identify clinically. The patient later developed focal seizures and epileptic spasms and had severe psychomotor delay. The present case suggests the occurrence of clinically silent seizures before the appearance of epileptic spasms in infants with tuberous sclerosis, and that EEG is an option for neonates with a prenatal diagnosis. PMID:26712128

  9. 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

  10. Sleep Related Hypermotor Seizures with a Right Parietal Onset.

    PubMed

    Gibbs, Steve A; Figorilli, Michela; Casaceli, Giuseppe; Proserpio, Paola; Nobili, Lino

    2015-08-01

    Nocturnal frontal lobe epilepsy (NFLE) is a syndrome characterized by the occurrence of sleep related seizures of variable complexity and duration. Hypermotor seizures (HMS) represent a classic manifestation of this syndrome, associated with a perturbation of the ventromesial frontal cortex and anterior cingulate gyrus regions. Nevertheless, in recent years, reports have showed that the seizure onset zone (SOZ) need not be of frontal origin to generate HMS. Here we report an unusual case of a patient presenting with a seven-year history of drug-resistant sleep related HMS arising from the mesial parietal region. The presence of an infrequent feeling of levitation before the HMS was key to suspecting a subtle focal cortical dysplasia in the right precuneus region. A stereo-EEG investigation confirmed the extra-frontal seizure onset of the HMS and highlighted the interrelationship between unstable sleep and seizure precipitation. PMID:25902821

  11. Pyramidal cells accumulate chloride at seizure onset

    PubMed Central

    Lillis, Kyle P; Kramer, Mark A; Mertz, Jerome; Staley, Kevin J

    2012-01-01

    Seizures are thought to originate from a failure of inhibition to quell hyperactive neural circuits, but the nature of this failure remains unknown. Here we combine high-speed two-photon imaging with electrophysiological recordings to directly evaluate the interaction between populations of interneurons and principal cells during the onset of seizure-like activity in mouse hippocampal slices. Both calcium imaging and dual patch clamp recordings reveal that in vitro seizure-like events (SLEs) are preceded by pre-ictal bursts of activity in which interneurons predominate. Corresponding changes in intracellular chloride concentration were observed in pyramidal cells using the chloride indicator Clomeleon. These changes were measurable at SLE onset and became very large during the SLE. Pharmacological manipulation of GABAergic transmission, either by blocking GABAA receptors or by hyperpolarizing the GABAA reversal potential, converted SLEs to short interictal-like bursts. Together, our results support a model in which pre-ictal GABAA receptor-mediated chloride influx shifts EGABA to produce a positive feedback loop that contributes to the initiation of seizure activity. PMID:22677032

  12. Positron emission tomography in generalized seizures

    SciTech Connect

    Theodore, W.H.; Brooks, R.; Margolin, R.; Patronas, N.; Sato, S.; Porter, R.J.; Mansi, L.; Bairamian, D.; DiChiro, G.

    1985-05-01

    The authors used /sup 18/F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to study nine patients with clinical absence or generalized seizures. One patient had only absence seizures, two had only generalized tonic-clonic seizures, and six had both seizure types. Interictal scans in eight failed to reveal focal or lateralized hypometabolism. No apparent abnormalities were noted. Two patients had PET scans after isotope injection during hyperventilation-induced generalized spike-wave discharges. Diffusely increased metabolic rates were found in one compared with an interictal scan, and in another compared with control values. Another patient had FDG injected during absence status: EEG showed generalized spike-wave discharges (during which she was unresponsive) intermixed with slow activity accompanied by confusion. Metabolic rates were decreased, compared with the interictal scan, throughout both cortical and subcortical structures. Interictal PET did not detect specific anatomic regions responsible for absence seizure onset in any patient, but the results of the ictal scans did suggest that pathophysiologic differences exist between absence status and single absence attacks.

  13. Failure of antiepileptic drugs in controlling seizures in epilepsy: What do we do next?

    PubMed

    Galindo-Mendez, Brahyan; Mayor, Luis C; Velandia-Hurtado, Fernando; Calderon-Ospina, Carlos

    2015-01-01

    Medically intractable epilepsy is a clinical condition of concern that arises when a patient with epilepsy suffers seizures, despite a trial of two or more antiepileptic drugs (AEDs) suitable for the type of epilepsy that are prescribed at maximum tolerated doses, does not achieve control of seizures. This diagnosis could be related to cortical dysplasias. We report the case of a 5-year-old girl with a previous normal neurological development and no family history of epilepsy who presented with focal-type seizures at age 4. She started treatment by taking different AEDs for seizure control. She continued having frequent seizures that sometimes progressed to generalized seizures and status epilepticus. After a focal cortical resection performed in the area where interictal spikes were detected, the pathology confirmed a type IIb cortical dysplasia as the cause of the epilepsy. This article discusses cortical dysplasias as a cause of pharmacoresistant epilepsy and its treatment. PMID:26101746

  14. 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. PMID:25944463

  15. [Seizures in newborn infant].

    PubMed

    Eskola, Vesa; Jäntti, Ville; Eriksson, Kai

    2010-01-01

    Seizures in newborn infants are common. The may constitute a neurologic emergency or a nonepileptic, harmless symptom. Diagnostics is becoming more specific with current methodologies. Detailed description of seizures and their connection with EEG abnormalities are the diagnostic cornerstones. The treatment has made slow progress, but newer antiepileptic drugs may aid in the treatment of epileptic seizures in newborn infants in the future. For the time being, evidence-based research results for them are lacking, as well as data on long-term effects. Differential diagnosis of seizures has become increasingly important. PMID:21188877

  16. Firing patterns of human limbic neurons during stereoencephalography (SEEG) and clinical temporal lobe seizures.

    PubMed

    Babb, T L; Wilson, C L; Isokawa-Akesson, M

    1987-06-01

    Comparisons of the patterns of neuronal firing and stereoencephalography (SEEG) recorded from the same microelectrodes chronically implanted in the human limbic system were made in order to study neuronal electrogenesis at onset and during propagation of focal partial complex seizures. Alert or sleeping patients were monitored during spontaneous subclinical seizures (no alterations in consciousness detectable), during auras reported by the patients as typical, and during clinical seizures with loss of consciousness, movements and post-ictal confusion. During subclinical SEEG seizures (ipsilateral, normal consciousness), few neurons increased firing (estimated at only 7%) either at the focus or at propagated sites. During auras, with altered consciousness, there were relatively few neurons that increased firing, with the estimate about 14% or twice as many as during a subclinical seizure. During the onset of a clinical seizure that involved loss of consciousness, movements and post-ictal confusion, many neurons were recruited into increased firing, with an estimate of approximately 36%. During this increased electrogenesis, neurons fired briefly in association with high-frequency local SEEG; however, the bursts were shorter than the SEEG seizure pattern. Apparently, other local neurons were recruited to fire in bursts to sustain sufficient axonal driving for widespread propagation of the seizure. When the focal SEEG slowed, the units stopped firing, which suggested that the 'focal' seizure need not be sustained for more than several seconds because propagated seizure activity was self-sustaining at distant structures. The data lead to the conclusion that SEEG seizures can be generated focally by synchronous firing of fewer than 10% of neurons in the 'epileptic pool.' However, when greater percentages of neurons are recruited in the 'epileptic focus' there is greater propagation to widespread sites, especially contralaterally, which will produce clinical partial

  17. Genes, Seizures & Epilepsy

    ERIC Educational Resources Information Center

    Goldman, Alica M.

    2006-01-01

    The chance that someone will develop any disease is influenced by heredity and environment. Epilepsy is not an exception. Everybody inherits a unique degree of susceptibility to seizures. About 3 percent of the United States population is prone to seizures and will get epilepsy at some point of their lives (1). Two thirds of the people with…

  18. Translational Development Strategy for Magnetic Seizure Therapy

    PubMed Central

    Rowny, Stefan; Benzl, Karla; Lisanby, Sarah H.

    2009-01-01

    Electroconvulsive therapy (ECT) has unparalleled antidepressant efficacy, but its cognitive side effects may be persistent. Research suggests that the side effects may be at least partially dissociable from the therapeutic effects of ECT, suggesting that distinct cortical networks may underlie them and introducing a role for focal seizure induction as a means of minimizing side effects. In magnetic seizure therapy (MST), magnetic fields avoid tissue impedance and induce electrical currents confined to superficial cortex, facilitating focal seizure induction. The translational development strategy for MST has included: (1) device development, (2) feasibility in animals and initial human trials, (3) testing in nonhuman primates on safety and mechanisms of action (with neuroanatomical, neurophysiological and cognitive endpoints), (4) safety testing in patients, (5) initial efficacy testing in patients, (6) dosage optimization, and (7) randomized comparison with ECT. These stages have been iterative, with results of early clinical testing prompting device enhancements that were, in turn, tested in nonhuman primates prior to human trials. Safety testing was aided by development of a nonhuman primate model of human ECT, and the validation of a cognitive battery for the monkey that is sensitive to the range of effects of ECT on human memory. Human testing has been facilitated by the development of an international consortium of centers addressing various aspects of technique and dose/response relationships. Challenges facing MST are common to other device based therapies: characterizing dose/response relationships, optimizing efficacy, and developing efficient and reliable methods to induce lasting therapeutic change in the circuitry underlying depression. PMID:19348798

  19. 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…

  20. 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

  1. Predictors and characteristics of seizures in survivors of progressive multifocal leukoencephalopathy.

    PubMed

    Miskin, Dhanashri P; Herman, Susan T; Ngo, Long H; Koralnik, Igor J

    2016-08-01

    This study aims to determine the risk factors for epileptogenesis and characteristics of seizures in patients with progressive multifocal leukoencephalopathy (PML) who survive more than 1 year from onset of neurological symptoms (PML survivors). We reviewed clinical data including seizure history and MR imaging studies from PML survivors evaluated at our institution between 1997 and 2014. PML progressors who passed away within 1 year and patients with a history of seizures prior to PML diagnosis were excluded from the analysis. Of 64 PML survivors, 28 (44 %) developed seizures. The median time from the onset of PML symptoms to the first seizure was 5.4 months (range 0-159) and 64 % of patients with seizures had them within the first year. The presence of juxtacortical PML lesions was associated with a relative risk of seizures of 3.5 (p < 0.02; 95 % confidence interval (CI) 1.3-9.4) in multivariate analyses. Of all seizure types, 86 % were focal and 60 % most likely originated from the frontal lobes. Among seizure patients, 89 % required treatment, including one (54 %), two (25 %), or three (10.5 %) antiepileptic drugs. Seizures are a frequent complication in PML and can develop throughout the entire course of the disease. However, late onset seizures did not signify PML relapse. Seizures may require treatment with multiple antiepileptic medications and are a significant co-morbidity in PML. PMID:26676826

  2. 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. PMID:26614397

  3. Immunological perspectives of temporal lobe seizures.

    PubMed

    Liimatainen, Suvi; Lehtimäki, Kai; Kai, Lehtimäki; Palmio, Johanna; Johanna, Palmio; Alapirtti, Tiina; Tiina, Alapirtti; Peltola, Jukka; Jukka, Peltola

    2013-10-15

    The temporal lobes are affected in many different neurological disorders, such as neurodegenerative diseases, viral and immunological encephalitides, and epilepsy. Both experimental and clinical evidence suggests a different inflammatory response to seizures in patients with temporal lobe epilepsy (TLE) in comparison to those with extra-TLE (XTLE). Proinflammatory cytokines and several autoantibodies have been shown to be associated with TLE compared to other epilepsy types suggesting the specific role and structure of the temporal lobe. Abundant experience suggests that activation of both innate and adaptive immunity is associated with epilepsy, particularly refractory focal epilepsy. Limbic encephalitis often triggers temporal lobe seizures, and a proportion of these disorders are immune-mediated. Histological evidence shows activation of specific inflammatory pathways in resected temporal lobes of epileptic patients, and certain epileptic disorders have shown increased incidence in patients with autoimmune diseases. Rapid activation of proinflammatory cytokines is observed after single seizures, but there is also evidence of chronic overproduction of cytokines and other inflammatory mediators in patients with TLE, suggesting a neuromodulatory role of inflammation in epilepsy. In this review we summarize current data on the presence and the role of immunological factors in temporal lobe seizures, and their possible involvement in epileptogenesis. PMID:23998423

  4. 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

  5. Effect of electroconvulsive seizures on cognitive flexibility.

    PubMed

    Svensson, Maria; Grahm, Matilda; Ekstrand, Joakim; Höglund, Peter; Johansson, Mikael; Tingström, Anders

    2016-07-01

    Electroconvulsive seizures (ECS), an animal model of electroconvulsive therapy, strongly stimulate hippocampal neurogenesis, but it is not known how this relates to the therapeutic effect or to the unwanted cognitive side effects. Recent findings suggest that neurogenesis might be important for flexible learning in changing environments. We hypothesize that animals receiving ECS treatment, which induces hippocampal neurogenesis, will show enhanced cognitive flexibility compared with controls. We have utilized a touch screen-based cognitive test (location discrimination (LD) task) to assess how five consecutive ECS treatments affect cognitive flexibility (measured as reversal of cognitive strategy) as well as spatial pattern separation ability. ECS-treated animals performed more reversals in the LD task earlier than controls over the 9 experimental weeks irrespective of spatial separation of visual stimuli, indicating an enhanced cognitive flexibility but unaffected pattern separation ability after ECS. We observed no correlation between hippocampal neurogenesis and the number of performed reversals during the last experimental week. This is the first study to elucidate the effect of ECS on cognitive flexibility. Our results indicate that ECS improves cognitive flexibility without affecting spatial pattern separation ability. Whether cognitive flexibility is enhanced via neurogenesis or other ECS-modulated processes, remains unknown. © 2016 Wiley Periodicals, Inc. PMID:26850212

  6. Efficacy of Retigabine on Acute Limbic Seizures in Adult Rats

    PubMed Central

    Friedman, LK; Slomko, AM; Wongvravit, JP; Naseer, Z; Hu, S; Wan, WY; Ali, SS

    2015-01-01

    Background and Purpose: The efficacy of retigabine (RGB), a positive allosteric modulator of K+ channels indicated for adjunct treatment of partial seizures, was studied in two adult models of kainic acid (KA)-induced status epilepticus to determine it’s toleratbility. Methods: Retigabine was administered systemiclly at high (5 mg/kg) and low (1–2 mg/kg) doses either 30 min prior to or 2 hr after KA-induced status epilepticus. High (1 µg/µL) and low (0.25 µg/µL) concentrations of RGB were also delivered by intrahippocampal microinjection in the presence of KA. Results: Dose-dependent effects of RGB were observed with both models. Lower doses increased seizure behavior latency and reduced the number of single spikes and synchronized burst events in the electroencephalogram (EEG). Higher doses worsened seizure behavior, produced severe ataxia, and increased spiking activity. Animals treated with RGB that were resistant to seizures did not exhibit significant injury or loss in GluR1 expression; however if stage 5–6 seizures were reached, typical hippocampal injury and depletion of GluR1 subunit protein in vulernable pyramidal fields occurred. Conclusions: RGB was neuroprotective only if seizures were significantly attenuated. GluR1 was simultaneously suppressed in the resistant granule cell layer in presence of RGB which may weaken excitatory transmission. Biphasic effects observed herein suggest that the human dosage must be carefully scrutinized to produce the optimal clinical response. PMID:26819936

  7. Beyond the CA1 subfield: Local hippocampal shape changes in MRI-negative temporal lobe epilepsy

    PubMed Central

    Maccotta, Luigi; Moseley, Emily D.; Benzinger, Tammie L.; Hogan, R. Edward

    2015-01-01

    Summary Objective Hippocampal atrophy in temporal lobe epilepsy (TLE) can indicate mesial temporal sclerosis and predict surgical success. Yet many TLE patients do not have significant atrophy (MRI-negative), presenting a diagnostic challenge. We used a new variant of high-dimensional large deformation mapping to assess whether patients with apparently normal hippocampi have local shape changes that mirror those of patients with significant hippocampal atrophy. Methods Forty-seven unilateral TLE patients and thirty-two controls underwent structural brain MRI. High-dimensional large deformation mapping provided hippocampal surface and volume estimates for each participant, dividing patients into low vs. high hippocampal atrophy groups. A vertex-level generalized linear model compared local shape changes between groups. Results Low atrophy TLE patients (MRI-negative) had significant local hippocampal shape changes compared to controls, similar to those in the contralateral hippocampus of high atrophy patients. These changes primarily involved the subicular and hilar/dentate regions, instead of the classically affected CA1 region. Disease duration instead covaried with lateral hippocampal atrophy, colocalizing with the CA1 subfield. Significance These findings show that “MRI-negative” TLE patients have regions of hippocampal atrophy that cluster medially, sparing the lateral regions (CA1) involved in high atrophy patients, suggesting an overall effect of temporal lobe seizures manifesting as bilateral medial hippocampal atrophy, and a more selective effect of hippocampal seizures leading to disease-proportional CA1 atrophy, potentially reflecting epileptogenesis. PMID:25809286

  8. Hypermotor seizures in lateral and mesial parietal epilepsy.

    PubMed

    Montavont, Alexandra; Kahane, Philippe; Catenoix, Hélène; Ostrowsky-Coste, Karine; Isnard, Jean; Guénot, Marc; Rheims, Sylvain; Ryvlin, Philippe

    2013-09-01

    Four patients with refractory epilepsy and hypermotor seizures (HMS) benefited from an intracerebral investigation after a presurgical evaluation and demonstrated an ictal onset zone primarily involving the posterior cortex, specifically the posterior cingulate gyrus in two patients. At seizure onset, these two patients reported a falling sensation, followed by HMSs characterized by swinging movements of the trunk with intense grasping of the bed railing. The two other patients with lateral parietal seizure onset reported blurred vision and dizziness, followed by a mixed pattern of the previously described type 1 and 2 HMSs. Three patients have been operated on, including two class I of Engel after 36 and 52months of follow-up. One patient developed a postoperative infection and continues to suffer seizures. Pathological findings disclosed a type IIa focal cortical dysplasia in all the patients. The last patient is awaiting surgery. Posterior cortex epilepsies, including those originating from the posterior cingulate cortex, can be responsible for HMSs. PMID:23872083

  9. Local cerebral metabolism during partial seizures

    SciTech Connect

    Engel, J. Jr.; Kuhl, D.E.; Phelps, M.E.; Rausch, R.; Nuwer, M.

    1983-04-01

    Interictal and ictal fluorodeoxyglucose scans were obtained with positron CT from four patients with spontaneous recurrent partial seizures, one with epilepsia partialis continua, and one with a single partial seizure induced by electrical stimulation of the hippocampus. Ictal metabolic patterns were different for each patient studied. Focal and generalized increased and decreased metabolism were observed. Ictal hypermetabolism may exceed six times the interictal rate and could represent activation of excitatory or inhibitory synapses in the epileptogenic region and its projection fields. Hypometabolism seen on ictal scans most likely reflects postictal depression and may indicate projection fields of inhibited neurons. No quantitative relationship between alterations in metabolism and EEG or behavioral measurements of ictal events could be demonstrated.

  10. Occipital seizures and subcortical T2 hypointensity in the setting of hyperglycemia

    PubMed Central

    Putta, Swapna L.; Weisholtz, Daniel; Milligan, Tracey A.

    2014-01-01

    Introduction Occipital lobe seizures are a recognized manifestation of diabetic nonketotic hyperglycemia, though not as common as focal motor seizures. Occipital lobe white matter T2 hypointensity may suggest this diagnosis. Methods We present a case of a 66-year-old man with hyperglycemia-related occipital lobe seizures who presented with confusion, intermittent visual hallucinations, and homonymous hemianopia. Results Magnetic resonance imaging showed subcortical T2 hypointensity within the left occipital lobe with adjacent leptomeningeal enhancement. These findings were transient with disappearance in a follow-up MRI. The EEG captured frequent seizures originating in the left occipital region. HbA1c level was 13.4% on presentation, and finger stick blood glucose level was 400 mg/dl. Conclusion Hyperglycemia should be considered in the etiology of differential diagnosis of patients with visual abnormalities suspicious for seizures, especially when the MRI shows focal subcortical T2 hypointensity with or without leptomeningeal enhancement. PMID:25667880

  11. 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

  12. Improving Early Seizure Detection

    PubMed Central

    Jouny, Christophe C.; Franaszczuk, Piotr J.; Bergey, Gregory K.

    2011-01-01

    Over the last decade, the search for a method able to reliably predict seizures hours in advance has been largely replaced by a more realistic goal of very early detection of seizure onset which would allow therapeutic or warning devices to be triggered prior to the onset of disabling clinical symptoms. We explore in this article the steps along the pathway from data acquisition to closed loop applications that can and should be considered to design the most efficient early seizure detection. Microelectrodes, high-frequency oscillations, high sampling rate, high-density arrays, and modern analysis techniques are all elements of the recording and detection process that in combination with modeling studies can provide new insights into the dynamics of seizure onsets. Each of these step needs to be considered if one wants to implement improved detection devices that will favorably impact the quality of life of patients. PMID:22078518

  13. Fibromyalgia and seizures.

    PubMed

    Tatum, William O; Langston, Michael E; Acton, Emily K

    2016-06-01

    The purpose of this case-matched study was to determine how frequently fibromyalgia is associated with different paroxysmal neurological disorders and explore the utility of fibromyalgia as a predictor for the diagnosis of psychogenic non-epileptic seizures. The billing diagnosis codes of 1,730 new, non-selected patient encounters were reviewed over a three-year period for an epileptologist in a neurology clinic to identify all patients with historical diagnoses of fibromyalgia. The frequency with which epileptic seizures, psychogenic non-epileptic seizures, and physiological non-epileptic events were comorbid with fibromyalgia was assessed. Age and gender case-matched controls were used for a between-group comparison. Wilcoxon tests were used to analyse interval data, and Chi-square was used to analyse categorical data (p<0.05). Fibromyalgia was retrospectively identified in 95/1,730 (5.5%) patients in this cohort. Females represented 95% of the fibromyalgia sample (age: 53 years; 95% CI: 57, 51). Forty-three percent of those with fibromyalgia had a non-paroxysmal, neurological primary clinical diagnosis, most commonly chronic pain. Paroxysmal events were present in 57% of fibromyalgia patients and 54% of case-matched controls. Among patients with fibromyalgia and paroxysmal disorders, 11% had epileptic seizures, 74% had psychogenic non-epileptic seizures, and 15% had physiological non-epileptic events, compared to case-matched controls with 37% epileptic seizures, 51% psychogenic non-epileptic events, and 12% physiological non-epileptic events (p = 0.009). Fibromyalgia was shown to be a predictor for the diagnosis of psychogenic non-epileptic seizures in patients with undifferentiated paroxysmal spells. However, our results suggest that the specificity and sensitivity of fibromyalgia as a marker for psychogenic non-epileptic seizures in a mixed general neurological population of patients is less than previously described. PMID:27238051

  14. On-off control of burst high frequency electrical stimulation to suppress 4-AP induced seizures

    NASA Astrophysics Data System (ADS)

    Chiang, Chia-Chu; Lin, Chou-Ching K.; Ju, Ming-Shaung

    2013-06-01

    Objective. The goal of this study was to investigate, using model simulations and animal experiments, the efficiency and the side effects of burst high frequency stimulation combined with on-off control in seizure suppression. Approach. A modified mathematical hippocampal seizure model was created to provide evidence of the eligibility of this approach. In the experimental setup, two recording electrodes were inserted into bilateral septal CA1 of the hippocampus, and a stimulation electrode was placed on the ventral hippocampal commissure of a rat. After seizures had been induced by 4-aminopyridine treatment, on-off control stimulation was used to suppress the seizures at 20 s intervals. The stimulation time, cumulative charge and post-stimulation suppression were used to assess the effects of burst duration. Main results. The results showed that burst stimulation could suppress the seizures during the control period and burst stimulation of a shorter duration could keep the seizure suppressed with less effort. By decreasing the burst duration, the cumulative stimulation time became shorter, the delivered cumulative charge became lower, and the cumulative time of post-stimulation suppression became longer. Significance. The on-off control stimulation not only prolonged the duration of suppression but also avoided the side effects of the conversion of seizure patterns. In particular, decreasing the specified burst duration increased the efficiency of the burst stimulation.

  15. Focal interictal epileptiform discharges in idiopathic generalized epilepsy.

    PubMed

    Esmail, Eman H; Nawito, Amani M; Labib, Dalia M; Basheer, Mye A

    2016-07-01

    Are idiopathic generalized epilepsies (IGEs) truly generalized? Do IGEs represent a continuum or rather distinct syndromes? Focal changes in the electroencephalography (EEG) have been reported in IGEs. The aim of this work is to investigate focal interictal epileptiform discharges (IEDs) in IGEs, and their relation to clinical variables. Forty-one IGE patients (classified according to ILAE, 2001) were recruited from a tertiary center (age 23 ± 10.938 years). Their files were reviewed and they were subjected to clinical examination and interictal EEG. Patients with focal IEDs were compared to those without focal IEDs. Nine patients had juvenile myoclonic epilepsy (JME) and 32 had idiopathic epilepsy with generalized tonic-clonic seizures only (EGTCSA). Focal IEDs were found in 20 patients, mostly in the frontal (45.5 %) and temporal (31.8 %) distribution. Patients with focal IEDs were treated with a larger number of combined antiepileptic drugs (AEDs) (p value = 0.022). No significant difference was found between the two groups regarding age, sex, age at onset, epilepsy syndrome, seizure frequency, family history, AEDs used (sodium valproate and carbamazepine) and their doses. Seventeen EGTCSA patients had focal IEDs. They were treated with larger number of combined AEDs (p value = 0.0142). No significant difference was found between the EGTCSA patients with and those without focal IEDs regarding age, sex, age at onset, seizure frequency, family history and AEDs doses. Caution must be applied in the interpretation of interictal focal IEDs. These focal changes may be related to prognosis, however this needs further investigation. PMID:26956566

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

    PubMed Central

    Mirrione, Martine M.; Konomos, Dorothy K.; Gravanis, Iordanis; Dewey, Stephen L.; Aguzzi, Adriano; Heppner, Frank L.; Tsirka, Stella E.

    2010-01-01

    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 hours prior to acute seizure), we observed a significant pro-convulsant phenomenon. This effect was associated with lower metabolic activation 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 hours prior to seizure induction may have a protective effect which is abolished by unilateral hippocampal microglia/macrophage ablation. PMID:20382223

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

    SciTech Connect

    Mirrione, M.M.; Mirrione, M.M.; Konomosa, D.K.; Ioradanis, G.; Dewey, S.L.; Agzzid, A.; Heppnerd, F.L.; Tsirka, St.E.

    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 activation 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.

  18. Hippocampal abnormalities after prolonged febrile convulsion: a longitudinal MRI study.

    PubMed

    Scott, Rod C; King, Martin D; Gadian, David G; Neville, Brian G R; Connelly, Alan

    2003-11-01

    Mesial temporal sclerosis (MTS) is the most common lesion in patients who require epilepsy surgery, and approximately 50% of patients with MTS have a history of prolonged febrile convulsion (PFC) in childhood. The latter led to the hypothesis that convulsive status epilepticus, including PFC, can cause MTS. Our recently published data on children investigated within 5 days of a PFC showed that children investigated by MRI within 48 h of a PFC had large hippocampal volumes and prolongation of T2 relaxation time. Patients investigated >48 h from a PFC had large hippocampal volumes and normal T2 relaxation time. These data are strongly suggestive of hippocampal oedema that is resolving within 5 days of a PFC, but do not exclude the possibility of a pre-existing hippocampal lesion. Fourteen children from the original study had follow-up investigations carried out 4-8 months after the acute investigations. Of the 14 patients, four have had further seizures. Two had short febrile convulsions, one had PFC and one had non-febrile seizures. There was a significant reduction in hippocampal volume and T2 relaxation time between the first and second investigations, and there is now no difference in hippocampal volume or T2 relaxation time in patients compared with a control population. Moreover, there is a significant increase in hippocampal volume asymmetry in patients at follow-up when compared with initial data. Five out of 14 patients had asymmetry outside the 95th percentile for control subjects and, of these, three had one hippocampal volume outside the lower 95% prediction limit for control subjects. A reduction in hippocampal volume or T2 relaxation time, into or below the normal range between the first and second scans, indicates that the earlier findings are temporary and are strongly suggestive of hippocampal oedema as the abnormality in the initial investigations. The change in hippocampal symmetry in the patient group is consistent with injury and neuronal loss

  19. A patient with atonic seizures mimicking transient ischemic attacks

    PubMed Central

    Kang, Min-Ju; Choi, Jun Young; An, Young-Sil; Park, Ki-Hyung; Park, Hyeon-Mi; Lee, Yeong-Bae; Shin, Dong-Jin; Sung, Young Hee; Shin, Dong Hoon

    2015-01-01

    A focal atonic seizure is a partial seizure in which the ictal manifestation consists of paresis of the extremities or muscles on one side of the body, and this phenomenon can easily be misdiagnosed as a transient ischemic attack. An 86-year-old woman visited our hospital complaining of transient right upper extremity weakness lasting for 10 min following an unusual sensation in her chest accompanied by palpitations. On the third hospital day, she again complained of right arm weakness, which progressed to jerky movements of her right extremity accompanied by facial twitching and then generalized into a tonic–clonic seizure. The EEG displayed several interictal spikes in the contralateral temporal area, and the ictal SPECT, analyzed using the SISCOM system, showed an increased signal in both the contralateral superior parietal area and the mesial frontal area. In this case, the patient was diagnosed with focal atonic seizures as the cause of the monolimb weakness, which had been initially misdiagnosed aas transient ischemic attacks. In cases in which a patient presents with monolimb paresis, physicians should consider the possibility of an atonic seizure as the cause. PMID:25870790

  20. Early-Onset Convulsive Seizures Induced by Brain Hypoxia-Ischemia in Aging Mice: Effects of Anticonvulsive Treatments

    PubMed Central

    Peng, Jessie; Patel, Nisarg; Huang, Yayi; Gao, Xiaoxing; Aljarallah, Salman; Eubanks, James H.; McDonald, Robert; Zhang, Liang

    2015-01-01

    Aging is associated with an increased risk of seizures/epilepsy. Stroke (ischemic or hemorrhagic) and cardiac arrest related brain injury are two major causative factors for seizure development in this patient population. With either etiology, seizures are a poor prognostic factor. In spite of this, the underlying pathophysiology of seizure development is not well understood. In addition, a standardized treatment regimen with anticonvulsants and outcome assessments following treatment has yet to be established for these post-ischemic seizures. Previous studies have modeled post-ischemic seizures in adult rodents, but similar studies in aging/aged animals, a group that mirrors a higher risk elderly population, remain sparse. Our study therefore aimed to investigate early-onset seizures in aging animals using a hypoxia-ischemia (HI) model. Male C57 black mice 18-20-month-old underwent a unilateral occlusion of the common carotid artery followed by a systemic hypoxic episode (8% O2 for 30 min). Early-onset seizures were detected using combined behavioral and electroencephalographic (EEG) monitoring. Brain injury was assessed histologically at different times post HI. Convulsive seizures were observed in 65% of aging mice post-HI but not in control aging mice following either sham surgery or hypoxia alone. These seizures typically occurred within hours of HI and behaviorally consisted of jumping, fast running, barrel-rolling, and/or falling (loss of the righting reflex) with limb spasms. No evident discharges during any convulsive seizures were seen on cortical-hippocampal EEG recordings. Seizure development was closely associated with acute mortality and severe brain injury on brain histological analysis. Intra-peritoneal injections of lorazepam and fosphenytoin suppressed seizures and improved survival but only when applied prior to seizure onset and not after. These findings together suggest that seizures are a major contributing factor to acute mortality in aging

  1. Seizures in Alzheimer's disease.

    PubMed

    Born, H A

    2015-02-12

    Alzheimer's disease (AD) increases the risk for late-onset seizures and neuronal network abnormalities. An elevated co-occurrence of AD and seizures has been established in the more prevalent sporadic form of AD. Recent evidence suggests that nonconvulsive network abnormalities, including seizures and other electroencephalographic abnormalities, may be more commonly found in patients than previously thought. Patients with familial AD are at an even greater risk for seizures, which have been found in patients with mutations in PSEN1, PSEN2, or APP, as well as with APP duplication. This review also provides an overview of seizure and electroencephalography studies in AD mouse models. The amyloid-β (Aβ) peptide has been identified as a possible link between AD and seizures, and while Aβ is known to affect neuronal activity, the full-length amyloid precursor protein (APP) and other APP cleavage products may be important for the development and maintenance of cortical network hyperexcitability. Nonconvulsive epileptiform activity, such as seizures or network abnormalities that are shorter in duration but may occur with higher frequency, may contribute to cognitive impairments characteristic of AD, such as amnestic wandering. Finally, the review discusses recent studies using antiepileptic drugs to rescue cognitive deficits in AD mouse models and human patients. Understanding the mechanistic link between epileptiform activity and AD is a research area of growing interest. Further understanding of the connection between neuronal hyperexcitability and Alzheimer's as well as the potential role of epileptiform activity in the progression of AD will be beneficial for improving treatment strategies. PMID:25484360

  2. Epileptic spasms without hypsarrhythmia in infancy and childhood: tonic spasms as a seizure type.

    PubMed

    Marchi, Luciana R De; Seraphim, Evelyn A; Corso, Jeana T; Naves, Pedro Vf; Carvalho, Kelly Cristina de; Ramirez, Milton David H; Ferrari-Marinho, Taissa; Guaranha, Mirian Sb; Yacubian, Elza Márcia T

    2015-06-01

    Epileptic spasms were defined by the International League Against Epilepsy Task Force on Classification and Terminology in 2001 as a specific seizure type. Epileptic spasms without hypsarrhythmia have been described in some series of patients, occurring either in infancy or childhood. More prolonged epileptic spasms without hypsarrhythmia were previously defined as a different seizure type, and referred to as "tonic spasm seizures". Here, we present a 5-year-old boy who started having epileptic spasms without hypsarrhythmia at 8 months of age, effectively treated with oxcarbazepine. With the withdrawal of medication, epileptic spasms returned. Video-EEG monitoring revealed high-voltage slow waves superimposed by low-voltage fast activity, followed by an electrodecremental phase and a burst of asymmetric fast activity, time-locked to clinical tonic spasm seizures. Brain MRI showed left temporal atrophy with temporal pole grey/white matter junction blurring and ictal PET-CT showed left basal frontal hypermetabolism. Seizures were refractory to several AEDs and vigabatrin was introduced with seizure cessation. Despite efforts to classify epileptic spasms, these are still considered as part of the group of unknown seizure types. In some cases, a focal origin has been suggested, leading to the term "periodic spasms" and "focal spasms". In this case, epileptic spasms without hypsarrhythmia, associated with tonic spasms, may be a variant of focal spasms and might be considered as an epileptic syndrome. [Published with video sequence]. PMID:25895540

  3. Dual effects of limbic seizures on psychosis-relevant behaviors shown by nucleus accumbens kindling in rats

    PubMed Central

    Ma, Jingyi; Leung, L. Stan

    2016-01-01

    Background A paradox in epilepsy and psychiatry is that temporal lobe epilepsy is often predisposed to schizophrenic-like psychosis, whereas convulsive therapy can relieve schizophrenic symptoms. We have previously demonstrated that the nucleus accumbens is a key structure in mediating postictal psychosis induced by a hippocampal electrographic seizure. Objective/Hypothesis The purpose of this study is to test a hypothesis that accumbens kindling cumulating in a single (1-time) or repeated (5-times) convulsive seizures have different effects on animal models of psychosis. Methods Electrical stimulation at 60 Hz was applied to nucleus accumbens to evoke afterdischarges until one, or five, convulsive seizures that involved the hind limbs (stage 5 seizures) were attained. Behavioral tests, performed at 3 days after the last seizure, included gating of hippocampal auditory evoked potentials (AEP) and prepulse inhibition to an acoustic startle response (PPI), tested without drug injection or after ketamine (3 mg/kg s.c.) injection, as well as locomotion induced by ketamine or methamphetamine (1 mg/kg i.p.). Results Compared to non-kindled control rats, 1-time, but not 5-times, convulsive seizures induced PPI deficit and decreased gating of hippocampal AEP, without drug injection. Compared to non-kindled rats, 5-times, but not 1-time, convulsive seizures antagonized ketamine-induced hyperlocomotion, ketamine-induced PPI deficit and AEP gating decrease. However, both 1- and 5-times convulsive seizures, significantly enhanced methamphetamine-induced locomotion as compared to non-kindled rats. Conclusions Accumbens kindling ending with 1 convulsive seizure may induce schizophrenic-like behaviors, while repeated (≥ 5) convulsive seizures induced by accumbens kindling may have therapeutic effects on dopamine independent psychosis. PMID:27267861

  4. 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…

  5. Sleep Related Hypermotor Seizures with a Right Parietal Onset

    PubMed Central

    Gibbs, Steve A.; Figorilli, Michela; Casaceli, Giuseppe; Proserpio, Paola; Nobili, Lino

    2015-01-01

    Nocturnal frontal lobe epilepsy (NFLE) is a syndrome characterized by the occurrence of sleep related seizures of variable complexity and duration. Hypermotor seizures (HMS) represent a classic manifestation of this syndrome, associated with a perturbation of the ventromesial frontal cortex and anterior cingulate gyrus regions. Nevertheless, in recent years, reports have showed that the seizure onset zone (SOZ) need not be of frontal origin to generate HMS. Here we report an unusual case of a patient presenting with a seven-year history of drug-resistant sleep related HMS arising from the mesial parietal region. The presence of an infrequent feeling of levitation before the HMS was key to suspecting a subtle focal cortical dysplasia in the right precuneus region. A stereo-EEG investigation confirmed the extra-frontal seizure onset of the HMS and highlighted the interrelationship between unstable sleep and seizure precipitation. Citation: Gibbs SA, Figorilli M, Casaceli G, Proserpio P, Nobili L. Sleep related hypermotor seizures with a right parietal onset. J Clin Sleep Med 2015;11(8):953–955. PMID:25902821

  6. Acute and chronic pharmacological models of generalized absence seizures.

    PubMed

    Cortez, Miguel A; Kostopoulos, George K; Snead, O Carter

    2016-02-15

    This article reviews the contribution of pharmacologically induced acute and chronic animal models to our understanding of epilepsies featuring non-convulsive generalized seizures, the typical and atypical absence seizures. Typical absences comprise about 5% of all epilepsies regardless of age and the atypical ones are even more common. Although absence epilepsy was thought to be relatively benign, children with childhood epilepsy (CAE) turn out to have a high rate of pretreatment attention deficits that persist despite seizure freedom. The phenomenon of the absence seizure has long attracted research interest because of the clear temporal relationship of the conspicuous EEG rhythm of 3 Hz generalized spike and wave discharges (GSWD) and the parallel transient "loss of consciousness" characterizing these seizures which is time-locked with the GSWD. Indeed, clinical epileptologists, basic scientists and neurophysiologists have long recognized in GSWD a unique electrographic and behavioral marker of the genetic predisposition to most types of epilepsy. Interestingly, the subject is still controversial since it has recently been proposed that both classification terms of CAE currently in use: idiopathic and primary generalized, be abandoned - a point of debate. Both issues - underlying mechanisms and focal origin of absence seizures - may be further enlightened by observations in valid animal models. PMID:26343323

  7. 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

  8. Kindled seizures selectively reduce a subpopulation of (/sup 3/H)quinuclidinyl benzilate binding sites in rat dentate gyrus

    SciTech Connect

    Savage, D.D.; McNamara, J.O.

    1982-09-01

    Amygdala-kindled seizures reduced significantly the total number of (/sup 3/H)quinuclidinyl benzilate binding sites in both dentate and hippocampal gyri compared to electrode implanted unstimulated controls. Both high and low affinity carbachol displaceable binding site populations were significantly reduced in hippocampal gyrus. By contrast, a selective decline of low affinity sites was found in dentate gyrus membranes. The selectivity of the decline in dentate but not hippocampus gyrus underscores the specificity of this molecular response to amygdala-kindled seizures. We suggest that these receptor alterations underlie adaptive mechanisms which antagonize kindled epileptogenesis.

  9. Spatial cognition following early-life seizures in rats: Performance deficits are dependent on task demands.

    PubMed

    Barry, Jeremy M; Tian, Chengju; Spinella, Anthony; Page, Matias; Holmes, Gregory L

    2016-07-01

    Cognitive impairment is a common comorbidity in childhood epilepsy. Studies in rodents have demonstrated that frequent seizures during the first weeks of life result in impaired spatial cognition when the rats are tested as juvenile or adults. To determine if spatial cognitive deficits following early-life seizures are task-specific or similar across spatial tasks, we compared the effects of early-life seizures in two spatial assays: 1) the Morris water maze, a hippocampal-dependent task of spatial cognition and 2) the active avoidance task, a task that associates an aversive shock stimulus with a static spatial location that requires intact hippocampal-amygdala networks. Rats with early-life seizures tested as adults did not differ from control rats in the water maze. However, while animals with early-life seizures showed some evidence of learning the active avoidance task, they received significantly more shocks in later training trials, particularly during the second training day, than controls. One possibility for the performance differences between the tasks is that the active avoidance task requires multiple brain regions and that interregional communication could be affected by alterations in white matter integrity. However, there were no measurable group differences with regard to levels of myelination. The study suggests that elucidation of mild cognitive deficits seen following early-life seizures may be dependent on task features of active avoidance. PMID:27152463

  10. The role of estrogens in seizures and epilepsy: the bad guys or the good guys?

    PubMed

    Velísková, J

    2006-01-01

    Estrogens influence neuronal activity and are important for normal brain functions. Effects of estrogens on seizures are contradictory. It is commonly accepted that estrogens may increase neuronal excitability and thus mediate proconvulsant effects. However, clinical and animal data show that estrogen may also have no effect or anticonvulsant effects. The action of estrogens on seizures depends on various factors, such as treatment duration and latency prior to the seizure testing, estrogen dose, hormonal status (naïve vs gonadectomized animals), estrogenic substance, the region/neurotransmitter system involved, the seizure type/model used, and sex. Besides the effects on seizure susceptibility, estrogens may also play an important role in seizure-induced damage. Pretreatment with beta-estradiol in ovariectomized female rats has neuroprotective effects on status epilepticus-induced hippocampal damage and prevents the loss of inhibition in the dentate gyrus during the early post-status epilepticus period determined by the in vitro paired pulse paradigm. Several signaling pathways may be involved in the neuroprotective effects of beta-estradiol on status epilepticus-induced hippocampal damage but at least one of these pathways involves interactions with neuropeptide Y. PMID:16310960

  11. Teaching about Search and Seizure.

    ERIC Educational Resources Information Center

    Kelly, Cynthia A.

    1978-01-01

    Presents a six-step model to help teachers develop curriculum related to the Fourth Amendment (search and seizure). The model focuses on determining values and attitudes, defining valid and unreasonable search and seizure, recognizing a valid warrant, and using film to teach about search and seizure. Journal available from the American Bar…

  12. Methylxanthine-evoked perturbation of spontaneous and evoked activities in isolated newborn rat hippocampal networks.

    PubMed

    Ruangkittisakul, A; Sharopov, S; Kantor, C; Kuribayashi, J; Mildenberger, E; Luhmann, H J; Kilb, W; Ballanyi, K

    2015-08-20

    Treatment of apnea of prematurity with methylxanthines like caffeine, aminophylline or theophylline can evoke hippocampal seizures. However, it is unknown at which interstitial brain concentrations methylxanthines promote such neonatal seizures or interfere with physiological 'early network oscillations' (ENOs) that are considered as pivotal for maturation of hippocampal neural networks. We studied theophylline and caffeine effects on ENOs in CA3 neurons (CA3-ENOs) and CA3 electrical stimulation-evoked monosynaptic CA1 field potentials (CA1-FPs) in sliced and intact hippocampi, respectively, from 8 to 10-days-old rats. Submillimolar doses of theophylline and caffeine, blocking adenosine receptors and phosphodiesterase-4 (PDE4), did not affect CA3-ENOs, ENO-associated cytosolic Ca(2+) transients or CA1-FPs nor did they provoke seizure-like discharges. Low millimolar doses of theophylline (⩾1mM) or caffeine (⩾5mM), blocking GABAA and glycine receptors plus sarcoplasmic-endoplasmic reticulum Ca(2+) ATPase (SERCA)-type Ca(2+) ATPases, evoked seizure-like discharges with no indication of cytosolic Ca(2+) dysregulation. Inhibiting PDE4 with rolipram or glycine receptors with strychnine had no effect on CA3-ENOs and did not occlude seizure-like events as tested with theophylline. GABAA receptor blockade induced seizure-like discharges and occluded theophylline-evoked seizure-like discharges in the slices, but not in the intact hippocampi. In summary, submillimolar methylxanthine concentrations do not acutely affect spontaneous CA3-ENOs or electrically evoked synaptic activities and low millimolar doses are needed to evoke seizure-like discharges in isolated developing hippocampal neural networks. We conclude that mechanisms of methylxanthine-related seizure-like discharges do not involve SERCA inhibition-related neuronal Ca(2+) dysregulation, PDE4 blockade or adenosine and glycine receptor inhibition, whereas GABA(A) receptor blockade may contribute partially. PMID

  13. Seizure Prediction: Methods

    PubMed Central

    Carney, Paul R.; Myers, Stephen; Geyer, James D.

    2011-01-01

    Epilepsy, one of the most common neurological diseases, affects over 50 million people worldwide. Epilepsy can have a broad spectrum of debilitating medical and social consequences. Although antiepileptic drugs have helped treat millions of patients, roughly a third of all patients have seizures that are refractory to pharmacological intervention. The evolution of our understanding of this dynamic disease leads to new treatment possibilities. There is great interest in the development of devices that incorporate algorithms capable of detecting early onset of seizures or even predicting them hours before they occur. The lead time provided by these new technologies will allow for new types of interventional treatment. In the near future, seizures may be detected and aborted before physical manifestations begin. In this chapter we discuss the algorithms that make these devices possible and how they have been implemented to date. We also compare and contrast these measures, and review their individual strengths and weaknesses. Finally, we illustrate how these techniques can be combined in a closed-loop seizure prevention system. PMID:22078526

  14. Absence of seizures in Rasmussen encephalitis with active inflammation.

    PubMed

    Samanta, Debopam; Gokden, Murat; Albert, Gregory W

    2016-06-01

    Severe focal motor epilepsy is considered a clinical hallmark of Rasmussen encephalitis (RE). The authors report a 6-year-old girl with progressive right sided hemiparesis, loss of language skills, left sided hemispheric atrophy, and brain pathologic features characteristic for RE. The patient did not experience seizures over a 2year period after symptom onset and for several months during follow-up. This report expands the clinical spectrum of RE and suggests that seizures are not a universal symptom of RE. Our patient's quite remarkable neurologic deficits along with active inflammation in the absence of epilepsy supports that, at least in some individuals, unilateral hemispheric progressive inflammation can occur without active seizure activity. PMID:26775150

  15. Seizure prediction and its applications.

    PubMed

    Iasemidis, Leon D

    2011-10-01

    Epilepsy is characterized by intermittent, paroxysmal, hypersynchronous electrical activity that may remain localized and/or spread and severely disrupt the brain's normal multitask and multiprocessing function. Epileptic seizures are the hallmarks of such activity. The ability to issue warnings in real time of impending seizures may lead to novel diagnostic tools and treatments for epilepsy. Applications may range from a warning to the patient to avert seizure-associated injuries, to automatic timely administration of an appropriate stimulus. Seizure prediction could become an integral part of the treatment of epilepsy through neuromodulation, especially in the new generation of closed-loop seizure control systems. PMID:21939848

  16. Musicogenic seizures in Dravet syndrome.

    PubMed

    Sanchez-Carpintero, Rocio; Patiño-Garcia, Ana; Urrestarazu, Elena

    2013-07-01

    Dravet syndrome is an epileptic encephalopathy characterized by multiple types of seizures. We report the first case of musicogenic reflex seizures in a 7-year-old male with a mutation in the SCN1A gene causing Dravet syndrome. Reflex seizures have been reported in patients with Dravet syndrome provoked by body temperature elevation, looking at visual patterns, or under intermittent photic stimulation. The case we report widens the spectrum of reflex seizures recorded in patients with Dravet syndrome. Cortical hyperexcitability of genetic origin could explain the tendency of these patients to experience reflex seizures. PMID:23517304

  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. PMID:26785903

  18. Pilomotor seizures in temporal lobe epilepsy: A case report with sequential changes in magnetic resonance imaging☆

    PubMed Central

    Kurita, Tsugiko; Sakurai, Kotaro; Takeda, Youji; Kusumi, Ichiro

    2013-01-01

    Piloerection is a rare ictal manifestation of temporal lobe epilepsy. The case is a 38-year-old man with acute onset of repetitive pilomotor seizures. Lacking other symptoms implicating epileptic seizures, a month passed before he was diagnosed with epilepsy. Ictal electroencephalography revealed rhythmic waves in the right temporal area. Reversible magnetic resonance imaging (MRI) abnormalities were visible in the right hippocampus, right uncus, and right amygdala. The appropriate antiepileptic drug therapy made him seizure-free, but following MRI, he showed right hippocampal atrophy one year after seizure cessation. This case is significant in that we can follow sequential MRI from onset, and it is meaningful for considering the mesial temporal area as involved with piloerection. PMID:25667848

  19. Dysplastic Cerebellar Epilepsy: Complete Seizure Control Following Resection of a Ganglioglioma.

    PubMed

    Martins, William Alves; Paglioli, Eliseu; Hemb, Marta; Palmini, Andre

    2016-08-01

    Subcortical epilepsy has been a controversial issue, partially settled by evidence showing seizure generation in hypothalamic hamartomas and also by reports of seizures caused by cerebellar lesions. We report 4-year-old girl with right hemifacial seizures and autonomic phenomena, in whom MRI showed an irregular mass in the right cerebellar peduncle. Despite several unremarkable video-EEG recordings, seizure origin in the lesion was hypothesized. Complete resection was feasible, histopathology showed a ganglioglioma, and she has been seizure free for 3 years. A fine line separates these developmental tumors from focal cortical dysplasia, and the homogeneous presentation of this entity led us to propose the terminology dysplastic cerebellar epilepsy. PMID:26208704

  20. Extraction of motion strength and motor activity signals from video recordings of neonatal seizures.

    PubMed

    Karayiannis, N B; Srinivasan, S; Bhattacharya, R; Wise, M S; Frost, J D; Mizrahi, E M

    2001-09-01

    This paper presents two methods developed to extract quantitative information from video recordings of neonatal seizures in the form of temporal motion strength and motor activity signals. Motion strength signals are extracted by measuring the area of the body parts that move during the seizure and the relative speed of motion using a combination of spatiotemporal subband decomposition of video, nonlinear filtering, and segmentation. Motor activity signals are extracted by tracking selected anatomical sites during the seizure using a modified version of a feature-tracking procedure developed for video, known as the Kanade-Lucas-Tomasi (KLT) algorithm. The experiments indicate that the temporal signals produced by the proposed methods provide the basis for differentiating myoclonic from focal clonic seizures and distinguishing these types of neonatal seizures from normal infant behaviors. PMID:11585212

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

    PubMed

    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; Kirsch, Heidi E; Nagarajan, Srikantan S

    2015-08-01

    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

  2. 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…

  3. Ion dynamics during seizures

    PubMed Central

    Raimondo, Joseph V.; Burman, Richard J.; Katz, Arieh A.; Akerman, Colin J.

    2015-01-01

    Changes in membrane voltage brought about by ion fluxes through voltage and transmitter-gated channels represent the basis of neural activity. As such, electrochemical gradients across the membrane determine the direction and driving force for the flow of ions and are therefore crucial in setting the properties of synaptic transmission and signal propagation. Ion concentration gradients are established by a variety of mechanisms, including specialized transporter proteins. However, transmembrane gradients can be affected by ionic fluxes through channels during periods of elevated neural activity, which in turn are predicted to influence the properties of on-going synaptic transmission. Such activity-induced changes to ion concentration gradients are a feature of both physiological and pathological neural processes. An epileptic seizure is an example of severely perturbed neural activity, which is accompanied by pronounced changes in intracellular and extracellular ion concentrations. Appreciating the factors that contribute to these ion dynamics is critical if we are to understand how a seizure event evolves and is sustained and terminated by neural tissue. Indeed, this issue is of significant clinical importance as status epilepticus—a type of seizure that does not stop of its own accord—is a life-threatening medical emergency. In this review we explore how the transmembrane concentration gradient of the six major ions (K+, Na+, Cl−, Ca2+, H+and HCO3−) is altered during an epileptic seizure. We will first examine each ion individually, before describing how multiple interacting mechanisms between ions might contribute to concentration changes and whether these act to prolong or terminate epileptic activity. In doing so, we will consider how the availability of experimental techniques has both advanced and restricted our ability to study these phenomena. PMID:26539081

  4. 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

  5. Supernumerary phantom limb as a rare symptom of epileptic seizures--case report and literature review.

    PubMed

    Millonig, Alban; Bodner, Thomas; Donnemiller, Eveline; Wolf, Elisabeth; Unterberger, Iris

    2011-08-01

    Supernumerary phantom limbs, that is, the awareness of an illusory extra limb is a fascinating neurologic symptom that has been described in a number of neurologic diseases including stroke, spinal injury, and epilepsy. Herein we report a case of a 70-year-old male patient with new-onset focal seizures with left-sided supernumerary phantom arm and leg as the only seizure manifestation. Ictal single-photon emission computed tomography (SPECT) revealed a hyperperfusion in the right temporoparietal junction and allowed localization of the seizure-onset zone. This report is accompanied by a discussion of phenomenology and terminology in the context of existing literature. PMID:21740418

  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. An Scn1a epilepsy mutation in Scn8a alters seizure susceptibility and behavior.

    PubMed

    Makinson, Christopher D; Dutt, Karoni; Lin, Frank; Papale, Ligia A; Shankar, Anupama; Barela, Arthur J; Liu, Robert; Goldin, Alan L; Escayg, Andrew

    2016-01-01

    Understanding the role of SCN8A in epilepsy and behavior is critical in light of recently identified human SCN8A epilepsy mutations. We have previously demonstrated that Scn8a(med) and Scn8a(med-jo) mice carrying mutations in the Scn8a gene display increased resistance to flurothyl and kainic acid-induced seizures; however, they also exhibit spontaneous absence seizures. To further investigate the relationship between altered SCN8A function and epilepsy, we introduced the SCN1A-R1648H mutation, identified in a family with generalized epilepsy with febrile seizures plus (GEFS+), into the corresponding position (R1627H) of the mouse Scn8a gene. Heterozygous R1627H mice exhibited increased resistance to some forms of pharmacologically and electrically induced seizures and the mutant Scn8a allele ameliorated the phenotype of Scn1a-R1648H mutants. Hippocampal slices from heterozygous R1627H mice displayed decreased bursting behavior compared to wild-type littermates. Paradoxically, at the homozygous level, R1627H mice did not display increased seizure resistance and were susceptible to audiogenic seizures. We furthermore observed increased hippocampal pyramidal cell excitability in heterozygous and homozygous Scn8a-R1627H mutants, and decreased interneuron excitability in heterozygous Scn8a-R1627H mutants. These results expand the phenotypes associated with disruption of the Scn8a gene and demonstrate that an Scn8a mutation can both confer seizure protection and increase seizure susceptibility. PMID:26410685

  8. Potential predictors of hippocampal atrophy in Alzheimer's disease.

    PubMed

    Dhikav, Vikas; Anand, Kuljeet

    2011-01-01

    The hippocampus is a vulnerable and plastic brain structure that is damaged by a variety of stimuli, e.g. hypoxia, hypoperfusion, hypoglycaemia, stress and seizures. Alzheimer's disease is a common and important disorder in which hippocampal atrophy is reported. Indeed, the available evidence suggests that hippocampal atrophy is the starting point of the pathogenesis of Alzheimer's disease and a significant number of patients with hippocampal atrophy will develop Alzheimer's disease. Studies indicate that hippocampal atrophy has functional consequences, e.g. cognitive impairment. Deposition of tau protein, formation of neurofibrillary tangles and accumulation of β-amyloid (Aβ) contributes to hippocampal atrophy together with damage caused by several other factors. Some of the factors associated with the development of hippocampal atrophy in Alzheimer's disease have been identified, e.g. hypertension, diabetes mellitus, hyperlipidaemia, seizures, affective disturbances and stress, and more is being learnt about other factors. Hypertension can potentially damage the hippocampus through ischaemia caused by atherosclerosis and cerebral amyloid angiopathy. Diabetes can produce hippocampal lesions via both vascular and non-vascular pathologies and can reduce the threshold for hippocampal damage. Carriers of the apolipoprotein E (ApoE)-ε4 genotype have been shown to have greater mesial temporal atrophy and poorer memory functions than non-carriers. In addition to giving rise to abnormal lipid metabolism, the ApoE-ε4 allele can affect the course of Alzheimer's disease via both Aβ-dependent and -independent pathways. Repetitive seizures can increase Aβ-peptide production and cause neurotransmission dysfunction and cytoskeletal abnormalities or a combination of these. Affective disturbances and stress are proposed to increase corticosteroid-induced hippocampal damage in many different ways. In the absence of any specific markers for predicting Alzheimer's disease

  9. Simultaneous fMRI and local field potential measurements during epileptic seizures in medetomidine sedated rats using RASER pulse sequence

    PubMed Central

    Airaksinen, Antti M; Niskanen, Juha-Pekka; Chamberlain, Ryan; Huttunen, Joanna K; Nissinen, Jari; Garwood, Michael; Pitkänen, Asla; Gröhn, Olli

    2010-01-01

    Simultaneous electrophysiological and functional magnetic resonance imaging (fMRI) measurements of animal models of epilepsy are methodologically challenging, but essential to better understand abnormal brain activity and hemodynamics during seizures. In the present study, fMRI of medetomidine sedated rats was performed using novel Rapid Acquisition by Sequential Excitation and Refocusing (RASER) fast imaging pulse sequence and simultaneous local field potential (LFP) measurements during kainic acid (KA) induced seizures. The image distortion caused by the hippocampal measuring electrode was clearly seen in echo planar imaging (EPI) images, whereas no artifact was seen in RASER images. Robust blood oxygenation level dependent (BOLD) responses were observed in the hippocampus during KA induced seizures. The recurrent epileptic seizures were detected in the LFP signal after KA injection. The presented combination of deep electrode LFP measurements and fMRI under medetomidine anesthesia, that does not significantly suppress KA induced seizures, provides a unique tool for studying abnormal brain activity in rats. PMID:20725933

  10. Long-lasting hyperpolarization underlies seizure reduction by low frequency deep brain electrical stimulation

    PubMed Central

    Toprani, Sheela; Durand, Dominique M

    2013-01-01

    Mesial temporal lobe epilepsy (MTLE) is a common medically refractory neurological disease. Deep brain electrical stimulation (DBS) of grey matter has been used for MTLE with limited success. However, stimulation of a white matter tract connecting the hippocampi, the ventral hippocampal commissure (VHC), with low frequencies that simulate interictal discharges has shown promising results, with seizure reduction greater than 98% in bilateral hippocampi during stimulation and greater than 50% seizure reduction in bilateral hippocampi after treatment. A major hurdle to the implementation and optimization of this treatment is that the mechanisms of seizure reduction by low frequency electrical stimulation (LFS) are not known. The goal of this study is to understand how commissural fibre tract stimulation reduces bilateral hippocampal epileptic activity in an in vitro slice preparation containing bilateral hippocampi connected by the VHC. It is our hypothesis that electrical stimuli induce hyperpolarization lasting hundreds of milliseconds following each pulse which reduces spontaneous epileptic activity during each inter-stimulus interval (ISI). Stimulus-induced long-lasting-hyperpolarization (LLH) can be mediated by GABAB inhibitory post-synaptic potentials (IPSPs) or slow after-hyperpolarization (sAHP). To test the role of LLH in effective bilateral seizure reduction by fibre tract stimulation, we measured stimulus-induced hyperpolarization during LFS of the VHC using electrophysiology techniques. Antagonism of the GABAB IPSP and/or sAHP diminished stimulus-induced hyperpolarization concurrently with LFS efficacy (greater than 50% reduction). Blocking both the GABAB IPSP and sAHP simultaneously eliminated the effect of electrical stimulation on seizure reduction entirely. These data show that LFS of the VHC is an effective protocol for bilateral hippocampal seizure reduction and that its efficacy relies on the induction of long-lasting hyperpolarization mediated

  11. Contrasting effects of Na+, K+-ATPase activation on seizure activity in acute versus chronic models.

    PubMed

    Funck, V R; Ribeiro, L R; Pereira, L M; de Oliveira, C V; Grigoletto, J; Della-Pace, I D; Fighera, M R; Royes, L F F; Furian, A F; Larrick, J W; Oliveira, M S

    2015-07-01

    Epilepsy is a life-shortening brain disorder affecting approximately 1% of the worldwide population. Most epilepsy patients are refractory to currently available antiepileptic drugs (AEDs). Knowledge about the mechanisms underlying seizure activity and probing for new AEDs is fundamental to the discovery of new therapeutic strategies. Brain Na(+), K(+)-ATPase activity contributes to the maintenance of the electrochemical gradients underlying neuronal resting and action potentials as well as the uptake and release of neurotransmitters. Accordingly, a decrease of Na(+), K(+)-ATPase increases neuronal excitability and may predispose to appearing of seizure activity. In the present study, we tested the hypothesis that activation of Na(+), K(+)-ATPase activity with a specific antibody (DRRSAb) raised against a regulatory site in the α subunit would decrease seizure susceptibility. We found that incubation of hippocampal homogenates with DRRSAb (1 μM) increased total and α1 Na(+), K(+)-ATPase activities. A higher concentration (3 μM) increased total, α1 and α2/α3 Na(+), K(+)-ATPase activities. Intrahippocampal injection of DRRSAb decreased the susceptibility of post status epilepticus animals to pentylenetetrazol (PTZ)-induced myoclonic seizures. In contrast, administration of DRRSAb into the hippocampus of naïve animals facilitated the appearance of PTZ-induced seizures. Quantitative analysis of hippocampal electroencephalography (EEG) recordings revealed that DRRSAb increased the percentage of total power contributed by the delta frequency band (0-3 Hz) to a large irregular amplitude pattern of hippocampal EEG. On the other hand, we found no DRRSAb-induced changes regarding the theta functional state. Further studies are necessary to define the potential of Na(+), K(+)-ATPase activation as a new therapeutic approach for seizure disorders. PMID:25907445

  12. Amentoflavone protects hippocampal neurons: anti-inflammatory, antioxidative, and antiapoptotic effects

    PubMed Central

    Zhang, Zhen; Sun, Tao; Niu, Jian-guo; He, Zhen-quan; Liu, Yang; Wang, Feng

    2015-01-01

    Amentoflavone is a natural biflavone compound with many biological properties, including anti-inflammatory, antioxidative, and neuroprotective effects. We presumed that amentoflavone exerts a neuroprotective effect in epilepsy models. Prior to model establishment, mice were intragastrically administered 25 mg/kg amentoflavone for 3 consecutive days. Amentoflavone effectively prevented pilocarpine-induced epilepsy in a mouse kindling model, suppressed nuclear factor-κB activation and expression, inhibited excessive discharge of hippocampal neurons resulting in a reduction in epileptic seizures, shortened attack time, and diminished loss and apoptosis of hippocampal neurons. Results suggested that amentoflavone protected hippocampal neurons in epilepsy mice via anti-inflammation, antioxidation, and antiapoptosis, and then effectively prevented the occurrence of seizures. PMID:26330838

  13. TISSUE-PLASMINOGEN ACTIVATOR IS INDUCED AS AN IMMEDIATE-EARLY GENE DURING SEIZURE, KINDLING, AND LONG-TERM POTENTIATION

    EPA Science Inventory

    Activity-dependent genes in brain have been identified using differential screening of hippocampal cDNA library from rats exposed to metrazol seizures under conditions of superconduction. Five immediate early genes whose expression is elevated by neural activity were identified. ...

  14. Raloxifene protects against seizures and neurodegeneration in a mouse model mimicking epilepsy in postmenopausal woman.

    PubMed

    Pottoo, F H; Bhowmik, M; Vohora, D

    2014-12-18

    Epilepsy in menopausal women presents several challenges in the treatment including an increased risk of seizures due to hormone replacement therapy. We investigated the hypothesis if raloxifene, a selective oestrogen receptor modulator, could be employed to prevent behavioural seizures and morphological alterations in a mouse model mimicking epilepsy in postmenopausal women. Female mice were made ovotoxic by treatment with 4-vinylcyclohexene diepoxide (VCD) to mimic a postmenopausal state. They were then subjected to kainic acid (KA)-induced seizures and neurotoxicity, as assessed by microscopic examination of hippocampus, relevant to human temporal lobe epilepsy. VCD administration (for 15days followed by a drug-free period of 30days) induced ovotoxicity in mice as evidenced by reduced number of primary ovarian follicles. This was accompanied by a 62.4% reduction in serum oestradiol levels. The bone mineral density of ovotoxic mice, however, remained unaffected. Raloxifene (8mg/kg) reduced the seizure severity score in both normal and ovotoxic mice and protected against degeneration induced by KA in the CA3, CA1 sub-fields and hilus of the DG. Hippocampal TGF-β3 levels were not affected by any of the treatments. We show the potential protective role of raloxifene in preventing seizures and neuronal damage in a mouse model mimicking epilepsy in postmenopausal women which was found unrelated to hippocampal TGF-β3. Raloxifene might represent a novel therapeutic option for postmenopausal temporal lobe epileptic woman. PMID:25218046

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

    PubMed Central

    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. PMID:26609376

  16. 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. PMID:23536761

  17. Quantitative peri-ictal electrocorticography and long-term seizure outcomes in temporal lobe epilepsy.

    PubMed

    Park, Seong-Cheol; Lee, Sang Kun; Chung, Chun Kee

    2015-01-01

    We analyzed peri-ictal electrocorticography below 70 Hz by a semiautomatic quantitative method. Thirty-four patients with medically intractable temporal lobe epilepsy underwent chronic electrocorticography using subdural electrodes. The resection extent of cortices with maximum amplitude activities were compared between seizure outcome groups. In detected activity significantly related to seizure outcome, we analyzed waveforms with automated waveform amplitude analysis. Mann-Whitney U tests were used. Mean follow-up duration was 49.7 ± 18.2 months. The resection extents of maximum amplitude activities in theta bands during the period between -10 and -5s from the ictal onset were significantly different between seizure outcome groups (adjusted p=0.01, the Benjamini-Hochberg correction). Delta, alpha and beta bands were related to seizure outcome only without multiple comparison corrections (unadjusted p=0.02, 0.03 and 0.04). Waveform peak amplitudes greater than 200 μV tended to be more common in the seizure free group than in the non-seizure-free group (unadjusted p=0.06). Waveform peak amplitudes greater than 350 μV were significantly more common in the cortical dysplasia type I group than in the hippocampal sclerosis group (unadjusted p=0.03). The resection of theta band activities during the preictal period was most important for good seizure outcome in temporal lobe epilepsy. PMID:25524857

  18. Two Seizure-Onset Types Reveal Specific Patterns of High-Frequency Oscillations in a Model of Temporal Lobe Epilepsy

    PubMed Central

    Lévesque, Maxime; Salami, Pariya; Gotman, Jean; Avoli, Massimo

    2016-01-01

    High-frequency oscillations(HFOs; 80–500 Hz ) are thought to mirror the pathophysiological changes occurring in epileptic brains. However, the distribution of HFOs during seizures remains undefined. Here, we recorded from the hippocampal CA3 subfield, subiculum, entorhinal cortex, and dentate gyrus to quantify the occurrence of ripples (80–200 Hz) and fast ripples (250–500 Hz) during low-voltage fast-onset (LVF) and hypersynchronous-onset (HYP) seizures in the rat pilocarpine model of temporal lobe epilepsy. We discovered in LVF seizures that (1) progression from preictal to ictal activity was characterized in seizure-onset zones by an increase of ripple rates that were higher when compared with fast ripple rates and (2) ripple rates during the ictal period were higher compared with fast ripple rates in seizure-onset zones and later in regions of secondary spread. In contrast, we found in HYP seizures that (1) fast ripple rates increased during the preictal period and were higher compared with ripple rates in both seizure-onset zones and in regions of secondary spread and (2) they were still higher compared with ripple rates in both seizure-onset zones and regions of secondary spread during the ictal period. Our findings demonstrate that ripples and fast ripples show distinct time- and region-specific patterns during LVF and HYP seizures, thus suggesting that they play specific roles in ictogenesis. PMID:22993442

  19. Modern concepts of seizure modeling.

    PubMed

    Bernard, Christophe; Naze, Sebastien; Proix, Timothée; Jirsa, Viktor K

    2014-01-01

    Seizures are complex phenomena spanning multiple spatial and temporal scales, from ion dynamics to communication between brain regions, from milliseconds (spikes) to days (interseizure intervals). Because of the existence of such multiple scales, the experimental evaluation of the mechanisms underlying the initiation, propagation, and termination of epileptic seizures is a difficult problem. Theoretical models and numerical simulations provide new tools to investigate seizure mechanisms at multiple scales. In this chapter, we review different theoretical approaches and their contributions to our understanding of seizure mechanisms. PMID:25078501

  20. Seizures and Teens: The Practical Aspects of Managing Seizure Medications

    ERIC Educational Resources Information Center

    Shafer, Patricia Osborne; Israel, Beth

    2007-01-01

    Medications are the primary treatment for epilepsy, yet many teens and their families have problems managing seizure medicines. Fear of side effects, difficulties remembering to take medicines and figuring out how to take them are common challenges. Unfortunately, not taking medicine as prescribed can lead to breakthrough seizures, which in turn…

  1. Seizures and Teens: Using Technology to Develop Seizure Preparedness

    ERIC Educational Resources Information Center

    Shafer, Patricia O.; Schachter, Steven C.

    2007-01-01

    Most people learn about seizures from their doctors, but others know only what they have seen on television. Unfortunately, visits to doctor's office aren't long enough to learn all that is needed, and often times, doctors and nurses aren't available to teach this information. Seizures are often represented inaccurately and too dramatically on…

  2. Neuroimaging observations in a cohort of elderly manifesting with new onset seizures: Experience from a university hospital

    PubMed Central

    Sinha, Sanjib; Satishchandra, Parthasarathy; Kalband, Balaji Rameshrao; Bharath, Rose Dawn; Thennarasu, Kandavel

    2012-01-01

    Background: The occurrence of epilepsy is higher among elderly patients. The clinical manifestations of seizures, causes of epilepsy, and choice of anti-epileptic drugs (AEDs) are different in elderly people with epilepsy compared to the young. Aim: To evaluate the imaging (CT/MRI) observations in elderly patients manifesting with new-onset seizures. Materials and Methods: Two hundred and one elderly patients with new onset seizures, >60 years (age: 68.0 ± 7.5 years; M:F = 1.8:1) from Jan’ 07 to Jan’ 09, were prospectively recruited. Observations of cranial CT scan (n = 201) and MR imaging (n = 43) were analyzed. Results: The type of seizures included: Simple partial (42%), generalized tonic-clonic (30.3%), and complex partial (27.4%). The pattern of epilepsy syndromes were acute symptomatic (42.3%), remote symptomatic (18.4%), cryptogenic (37.8%), and idiopathic (1.5%). Seizures were controlled with monotherapy in 85%. The CT scan (n = 201) revealed cerebral atrophy (139), mild (79), moderate (43), and severe (18); focal lesions (98), infarcts (45), hemorrhages (18), granuloma (16), tumor (15) and gliosis (4), and hemispheric atrophy (1), white matter changes (75) and diffuse edema (21). An MRI (n = 43) showed variable degree of cerebral atrophy (31); white matter changes (20); focal cerebral lesions (24); - infarct (7); intracranial hemorrhage (6); granuloma (5); tumor (6); gliosis (1); hemispheric atrophy (1); and prominent Virchow-Robin spaces (7); and UBOs (12). Patients with focal lesions in neuroimaging more often had partial seizures, symptomatic epilepsy, past stroke, focal deficit, absence of diffuse atrophy, focal EEG slowing, abnormal CSF, seizure recurrence at follow-up (P < 0.05). Conclusions: Brain imaging observations in elderly patients with new-onset seizures revealed underlying symptomatic nature, hence the etiology and thereby assisted in deciding the specific therapy. PMID:23349592

  3. Febrile seizures - what to ask your doctor

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000223.htm Febrile seizures - what to ask your doctor To use the ... please enable JavaScript. Your child has had a febrile seizure. A simple febrile seizure stops by itself within ...

  4. Characterising seizures in anti-NMDA-receptor encephalitis with dynamic causal modelling

    PubMed Central

    Cooray, Gerald K.; Sengupta, Biswa; Douglas, Pamela; Englund, Marita; Wickstrom, Ronny; Friston, Karl

    2015-01-01

    We characterised the pathophysiology of seizure onset in terms of slow fluctuations in synaptic efficacy using EEG in patients with anti-N-methyl-d-aspartate receptor (NMDA-R) encephalitis. EEG recordings were obtained from two female patients with anti-NMDA-R encephalitis with recurrent partial seizures (ages 19 and 31). Focal electrographic seizure activity was localised using an empirical Bayes beamformer. The spectral density of reconstructed source activity was then characterised with dynamic causal modelling (DCM). Eight models were compared for each patient, to evaluate the relative contribution of changes in intrinsic (excitatory and inhibitory) connectivity and endogenous afferent input. Bayesian model comparison established a role for changes in both excitatory and inhibitory connectivity during seizure activity (in addition to changes in the exogenous input). Seizures in both patients were associated with a sequence of changes in inhibitory and excitatory connectivity; a transient increase in inhibitory connectivity followed by a transient increase in excitatory connectivity and a final peak of excitatory–inhibitory balance at seizure offset. These systematic fluctuations in excitatory and inhibitory gain may be characteristic of (anti NMDA-R encephalitis) seizures. We present these results as a case study and replication to motivate analyses of larger patient cohorts, to see whether our findings generalise and further characterise the mechanisms of seizure activity in anti-NMDA-R encephalitis. PMID:26032883

  5. Impaired consciousness in temporal lobe seizures: role of cortical slow activity

    PubMed Central

    Englot, Dario J.; Yang, Li; Hamid, Hamada; Danielson, Nathan; Bai, Xiaoxiao; Marfeo, Anthony; Yu, Lissa; Gordon, Aliza; Purcaro, Michael J.; Motelow, Joshua E.; Agarwal, Ravi; Ellens, Damien J.; Golomb, Julie D.; Shamy, Michel C. F.; Zhang, Heping; Carlson, Chad; Doyle, Werner; Devinsky, Orrin; Vives, Kenneth; Spencer, Dennis D.; Spencer, Susan S.; Schevon, Catherine; Zaveri, Hitten P.

    2010-01-01

    Impaired consciousness requires altered cortical function. This can occur either directly from disorders that impair widespread bilateral regions of the cortex or indirectly through effects on subcortical arousal systems. It has therefore long been puzzling why focal temporal lobe seizures so often impair consciousness. Early work suggested that altered consciousness may occur with bilateral or dominant temporal lobe seizure involvement. However, other bilateral temporal lobe disorders do not impair consciousness. More recent work supports a ‘network inhibition hypothesis’ in which temporal lobe seizures disrupt brainstem–diencephalic arousal systems, leading indirectly to depressed cortical function and impaired consciousness. Indeed, prior studies show subcortical involvement in temporal lobe seizures and bilateral frontoparietal slow wave activity on intracranial electroencephalography. However, the relationships between frontoparietal slow waves and impaired consciousness and between cortical slowing and fast seizure activity have not been directly investigated. We analysed intracranial electroencephalography recordings during 63 partial seizures in 26 patients with surgically confirmed mesial temporal lobe epilepsy. Behavioural responsiveness was determined based on blinded review of video during seizures and classified as impaired (complex-partial seizures) or unimpaired (simple-partial seizures). We observed significantly increased delta-range 1–2 Hz slow wave activity in the bilateral frontal and parietal neocortices during complex-partial compared with simple-partial seizures. In addition, we confirmed prior work suggesting that propagation of unilateral mesial temporal fast seizure activity to the bilateral temporal lobes was significantly greater in complex-partial than in simple-partial seizures. Interestingly, we found that the signal power of frontoparietal slow wave activity was significantly correlated with the temporal lobe fast seizure

  6. Impaired consciousness in temporal lobe seizures: role of cortical slow activity.

    PubMed

    Englot, Dario J; Yang, Li; Hamid, Hamada; Danielson, Nathan; Bai, Xiaoxiao; Marfeo, Anthony; Yu, Lissa; Gordon, Aliza; Purcaro, Michael J; Motelow, Joshua E; Agarwal, Ravi; Ellens, Damien J; Golomb, Julie D; Shamy, Michel C F; Zhang, Heping; Carlson, Chad; Doyle, Werner; Devinsky, Orrin; Vives, Kenneth; Spencer, Dennis D; Spencer, Susan S; Schevon, Catherine; Zaveri, Hitten P; Blumenfeld, Hal

    2010-12-01

    Impaired consciousness requires altered cortical function. This can occur either directly from disorders that impair widespread bilateral regions of the cortex or indirectly through effects on subcortical arousal systems. It has therefore long been puzzling why focal temporal lobe seizures so often impair consciousness. Early work suggested that altered consciousness may occur with bilateral or dominant temporal lobe seizure involvement. However, other bilateral temporal lobe disorders do not impair consciousness. More recent work supports a 'network inhibition hypothesis' in which temporal lobe seizures disrupt brainstem-diencephalic arousal systems, leading indirectly to depressed cortical function and impaired consciousness. Indeed, prior studies show subcortical involvement in temporal lobe seizures and bilateral frontoparietal slow wave activity on intracranial electroencephalography. However, the relationships between frontoparietal slow waves and impaired consciousness and between cortical slowing and fast seizure activity have not been directly investigated. We analysed intracranial electroencephalography recordings during 63 partial seizures in 26 patients with surgically confirmed mesial temporal lobe epilepsy. Behavioural responsiveness was determined based on blinded review of video during seizures and classified as impaired (complex-partial seizures) or unimpaired (simple-partial seizures). We observed significantly increased delta-range 1-2 Hz slow wave activity in the bilateral frontal and parietal neocortices during complex-partial compared with simple-partial seizures. In addition, we confirmed prior work suggesting that propagation of unilateral mesial temporal fast seizure activity to the bilateral temporal lobes was significantly greater in complex-partial than in simple-partial seizures. Interestingly, we found that the signal power of frontoparietal slow wave activity was significantly correlated with the temporal lobe fast seizure activity in

  7. Post-Traumatic Seizures Exacerbate Histopathological Damage after Fluid-Percussion Brain Injury

    PubMed Central

    Bao, Ying-hui; Bramlett, Helen M.; Atkins, Coleen M.; Truettner, Jessie S.; Lotocki, George; Alonso, Ofelia F.

    2011-01-01

    Abstract The purpose of this study was to investigate the effects of an induced period of post-traumatic epilepsy (PTE) on the histopathological damage caused by traumatic brain injury (TBI). Male Sprague Dawley rats were given a moderate parasagittal fluid-percussion brain injury (1.9–2.1 atm) or sham surgery. At 2 weeks after surgery, seizures were induced by administration of a GABAA receptor antagonist, pentylenetetrazole (PTZ, 30 mg/kg). Seizures were then assessed over a 1-h period using the Racine clinical rating scale. To evaluate whether TBI-induced pathology was exacerbated by the seizures, contusion volume and cortical and hippocampal CA3 neuronal cell loss were measured 3 days after seizures. Nearly all TBI rats showed clinical signs of PTE following the decrease in inhibitory activity. In contrast, clinically evident seizures were not observed in TBI rats given saline or sham-operated rats given PTZ. Contusions in TBI-PTZ-treated rats were significantly increased compared to the TBI-saline-treated group (p < 0.001). In addition, the TBI-PTZ rats showed less NeuN-immunoreactive cells within the ipsilateral parietal cerebral cortex (p < 0.05) and there was a trend for decreased hippocampal CA3 neurons in TBI-PTZ rats compared with TBI-saline or sham-operated rats. These results demonstrate that an induced period of post-traumatic seizures significantly exacerbates the structural damage caused by TBI. These findings emphasize the need to control seizures after TBI to limit even further damage to the injured brain. PMID:20836615

  8. 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

  9. [Seizure characteristics in Kawasaki disease].

    PubMed

    Shimakawa, Shuichi; Yamada, Katsuhiko; Hara, Keita; Tanabe, Takuya; Tamai, Hiroshi

    2008-07-01

    It is well known that convulsions may occur in clinical course of Kawasaki disease. However, the features of such seizures remain unclear. Recent reports have hypothesized that proinflammatory cytokines may contribute to the genesis of febrile convulsions (FC). In the acute phase of Kawasaki disease, proinflammatory cytokines are elevated in serum and CSF. If cytokines play a role in seizure phenomena in patients with Kawasaki disease, FC and seizures in Kawasaki disease might share some clinical features. To clarify the clinical features of convulsion in Kawasaki disease, we investigated 7 patients with Kawasaki disease with convulsions who were diagnosed and treated from November 2003 to November 2005. We found several features of the seizures, as well as the onset age, were diffrent among these clinical entities. The onset of Kawasaki disease was characteristically before six months of age in all patients. Seizure clustering was seen in 5 patients and partial seizures in 4. Prolonged unconsciousness after seizures was seen in one patient, syndrome of inappropriate secretion of ADH (SIADH) in one other. One patient had markedly elevated IL-6 in CSF. These observations led us to speculate that the convulsion of Kawasaki disease may be attributable to an encephalitis. The results of this study suggest that seizure pathophysiology differs between FC and Kawasaki disease. PMID:18634413

  10. Recurrent seizures after lidocaine ingestion.

    PubMed

    Aminiahidashti, Hamed; Laali, Abolghasem; Nosrati, Nazanin; Jahani, Fatemeh

    2015-01-01

    Lidocaine has a concentration-dependent effect on seizures. Concentrations above 15 μg/mL frequently result in seizures in laboratory animals and human. We report a case of central nervous system (CNS) lidocaine toxicity and recurrent seizure after erroneous ingestion of lidocaine solution. A 4-year-old boy presented to the Emergency Department of Imam Hospital of Sari in December 2013 due to tonic-clonic generalized seizures approximately 30 min ago. 3 h before seizure, his mother gave him 2 spoons (amount 20-25 cc) lidocaine hydrochloride 2% solution instead of pediatric gripe by mistake. Seizure with generalized tonic-clonic occurred 3 times in home. Neurological examination was essentially unremarkable except for the depressed level of consciousness. Personal and medical history was unremarkable. There was no evidence of intracranial ischemic or hemorrhagic lesions in computed tomography scan. There were no further seizures, the condition of the patient remained stable, and he was discharged 2 days after admission. The use of viscous lidocaine may result in cardiovascular and CNS toxicity, particularly in children. Conservative management is the best option for treatment of lidocaine induced seizure. PMID:25709968

  11. Recurrent seizures after lidocaine ingestion

    PubMed Central

    Aminiahidashti, Hamed; Laali, Abolghasem; Nosrati, Nazanin; Jahani, Fatemeh

    2015-01-01

    Lidocaine has a concentration-dependent effect on seizures. Concentrations above 15 μg/mL frequently result in seizures in laboratory animals and human. We report a case of central nervous system (CNS) lidocaine toxicity and recurrent seizure after erroneous ingestion of lidocaine solution. A 4-year-old boy presented to the Emergency Department of Imam Hospital of Sari in December 2013 due to tonic-clonic generalized seizures approximately 30 min ago. 3 h before seizure, his mother gave him 2 spoons (amount 20–25 cc) lidocaine hydrochloride 2% solution instead of pediatric gripe by mistake. Seizure with generalized tonic-clonic occurred 3 times in home. Neurological examination was essentially unremarkable except for the depressed level of consciousness. Personal and medical history was unremarkable. There was no evidence of intracranial ischemic or hemorrhagic lesions in computed tomography scan. There were no further seizures, the condition of the patient remained stable, and he was discharged 2 days after admission. The use of viscous lidocaine may result in cardiovascular and CNS toxicity, particularly in children. Conservative management is the best option for treatment of lidocaine induced seizure. PMID:25709968

  12. [Reflex seizures, cinema and television].

    PubMed

    Olivares-Romero, Jesús

    2015-12-16

    In movies and television series are few references to seizures or reflex epilepsy even though in real life are an important subgroup of total epileptic syndromes. It has performed a search on the topic, identified 25 films in which they appear reflex seizures. Most seizures observed are tonic-clonic and visual stimuli are the most numerous, corresponding all with flashing lights. The emotions are the main stimuli in higher level processes. In most cases it is not possible to know if a character suffers a reflex epilepsy or suffer reflex seizures in the context of another epileptic syndrome. The main conclusion is that, in the movies, the reflex seizures are merely a visual reinforcing and anecdotal element without significant influence on the plot. PMID:26662874

  13. Predicting Epileptic Seizures in Advance

    PubMed Central

    Moghim, Negin; Corne, David W.

    2014-01-01

    Epilepsy is the second most common neurological disorder, affecting 0.6–0.8% of the world's population. In this neurological disorder, abnormal activity of the brain causes seizures, the nature of which tend to be sudden. Antiepileptic Drugs (AEDs) are used as long-term therapeutic solutions that control the condition. Of those treated with AEDs, 35% become resistant to medication. The unpredictable nature of seizures poses risks for the individual with epilepsy. It is clearly desirable to find more effective ways of preventing seizures for such patients. The automatic detection of oncoming seizures, before their actual onset, can facilitate timely intervention and hence minimize these risks. In addition, advance prediction of seizures can enrich our understanding of the epileptic brain. In this study, drawing on the body of work behind automatic seizure detection and prediction from digitised Invasive Electroencephalography (EEG) data, a prediction algorithm, ASPPR (Advance Seizure Prediction via Pre-ictal Relabeling), is described. ASPPR facilitates the learning of predictive models targeted at recognizing patterns in EEG activity that are in a specific time window in advance of a seizure. It then exploits advanced machine learning coupled with the design and selection of appropriate features from EEG signals. Results, from evaluating ASPPR independently on 21 different patients, suggest that seizures for many patients can be predicted up to 20 minutes in advance of their onset. Compared to benchmark performance represented by a mean S1-Score (harmonic mean of Sensitivity and Specificity) of 90.6% for predicting seizure onset between 0 and 5 minutes in advance, ASPPR achieves mean S1-Scores of: 96.30% for prediction between 1 and 6 minutes in advance, 96.13% for prediction between 8 and 13 minutes in advance, 94.5% for prediction between 14 and 19 minutes in advance, and 94.2% for prediction between 20 and 25 minutes in advance. PMID:24911316

  14. Audiogenic reflex seizures in cats

    PubMed Central

    Lowrie, Mark; Bessant, Claire; Harvey, Robert J; Sparkes, Andrew; Garosi, Laurent

    2015-01-01

    Objectives This study aimed to characterise feline audiogenic reflex seizures (FARS). Methods An online questionnaire was developed to capture information from owners with cats suffering from FARS. This was collated with the medical records from the primary veterinarian. Ninety-six cats were included. Results Myoclonic seizures were one of the cardinal signs of this syndrome (90/96), frequently occurring prior to generalised tonic–clonic seizures (GTCSs) in this population. Other features include a late onset (median 15 years) and absence seizures (6/96), with most seizures triggered by high-frequency sounds amid occasional spontaneous seizures (up to 20%). Half the population (48/96) had hearing impairment or were deaf. One-third of cats (35/96) had concurrent diseases, most likely reflecting the age distribution. Birmans were strongly represented (30/96). Levetiracetam gave good seizure control. The course of the epilepsy was non-progressive in the majority (68/96), with an improvement over time in some (23/96). Only 33/96 and 11/90 owners, respectively, felt the GTCSs and myoclonic seizures affected their cat’s quality of life (QoL). Despite this, many owners (50/96) reported a slow decline in their cat’s health, becoming less responsive (43/50), not jumping (41/50), becoming uncoordinated or weak in the pelvic limbs (24/50) and exhibiting dramatic weight loss (39/50). These signs were exclusively reported in cats experiencing seizures for >2 years, with 42/50 owners stating these signs affected their cat’s QoL. Conclusions and relevance In gathering data on audiogenic seizures in cats, we have identified a new epilepsy syndrome named FARS with a geriatric onset. Further studies are warranted to investigate potential genetic predispositions to this condition. PMID:25916687

  15. Seizure Treatment in Transplant Patients

    PubMed Central

    Shepard, Paul W.

    2013-01-01

    Opinion statement Solid organ transplantation is frequently complicated by a spectrum of seizure types, including single partial-onset or generalized tonic-clonic seizures, acute repetitive seizures or status epilepticus, and sometimes the evolution of symptomatic epilepsy. There is currently no specific evidence involving the transplant patient population to guide the selection, administration, or duration of antiepileptic drug (AED) therapy, so familiarity with clinical AED pharmacology and application of sound judgment are necessary for successful patient outcomes. An initial detailed search for symptomatic seizure etiologies, including metabolic, infectious, cerebrovascular, and calcineurin inhibitor treatment-related neuro-toxic complications such as posterior reversible encephalopathy syndrome (PRES), is imperative, as underlying central nervous system disorders may impose additional serious risks to cerebral or general health if not promptly detected and appropriately treated. The mainstay for post-transplant seizure management is AED therapy directed toward the suspected seizure type. Unfavorable drug interactions could place the transplanted organ at risk, so choosing an AED with limited interaction potential is also crucial. When the transplanted organ is dysfunctional or vulnerable to rejection, AEDs without substantial hepatic metabolism are favored in post-liver transplant patients, whereas after renal transplantation, AEDs with predominantly renal elimination may require dosage adjustment to prevent adverse effects. Levetiracetam, gabapentin, pregabalin, and lacosamide are drugs of choice for treatment of partial-onset seizures in post-transplant patients given their efficacy spectrum, generally excellent tolerability, and lack of drug interaction potential. Levetiracetam is the drug of choice for primary generalized seizures in post-transplant patients. When intravenous drugs are necessary for acute seizure management, benzodiazepines and

  16. Imaging the seizure onset zone with stereo-electroencephalography.

    PubMed

    David, Olivier; Blauwblomme, Thomas; Job, Anne-Sophie; Chabardès, Stéphan; Hoffmann, Dominique; Minotti, Lorella; Kahane, Philippe

    2011-10-01

    Stereo-electroencephalography is used to localize the seizure onset zone and connected neuronal networks in surgical candidates suffering from intractable focal epilepsy. The concept of an epileptogenicity index has been proposed recently to represent the likelihood of various regions being part of the seizure onset zone. It quantifies low-voltage fast activity, the electrophysiological signature of seizure onset usually assessed visually by neurologists. Here, we revisit epileptogenicity in light of neuroimaging tools such as those provided in statistical parametric mapping software. Our goal is to propose a robust approach, allowing easy exploration of patients' brains in time and space. The procedure is based upon statistical parametric mapping, which is an established framework for comparing multi-dimensional image data that allows one to correct for inherent multiple comparisons. Statistics can also be performed at the group level, between seizures in the same patient or between patients suffering from the same type of epilepsy using normalization of brains to a common anatomic atlas. Results are obtained from three case studies (insular reflex epilepsy, cryptogenic frontal epilepsy and lesional occipital epilepsy) where tailored resection was performed, and from a group of 10 patients suffering from mesial temporal lobe epilepsy. They illustrate the basics of the technique and demonstrate its very good reproducibility and specificity. Most importantly, the proposed approach to the quantification of the seizure onset zone allows one to summarize complex signals in terms of a time-series of statistical parametric maps that can support clinical decisions. Quantitative neuroimaging of stereo-electroencephalographic features of seizures might thus help to provide better pre-surgical assessment of patients undergoing resective surgery. PMID:21975587

  17. Dynamic seizure-related changes in extracellular signal-regulated kinase activation in a mouse model of temporal lobe epilepsy

    PubMed Central

    Houser, Carolyn R.; Huang, Christine S.; Peng, Zechun

    2008-01-01

    Extracellular signal-regulated kinase (ERK) is highly sensitive to regulation by neuronal activity and is critically involved in several forms of synaptic plasticity. These features suggested that alterations in ERK signaling might occur in epilepsy. Previous studies have described increased ERK phosphorylation immediately after the induction of severe seizures, but patterns of ERK activation in epileptic animals during the chronic period have not been determined. Thus, the localization and abundance of phosphorylated ERK (pERK) were examined in a pilocarpine model of recurrent seizures in C57BL/6 mice during the seizure-free period and at short intervals after spontaneous seizures. Immunolabeling of pERK in control animals revealed an abundance of distinctly-labeled neurons within the hippocampal formation. However, in pilocarpine-treated mice during the seizure-free period, the numbers of pERK-labeled neurons were substantially decreased throughout much of the hippocampal formation. Double labeling with a general neuronal marker suggested that the decrease in pERK-labeled neurons was not due primarily to cell loss. The decreased ERK phosphorylation in seizure-prone animals was interpreted as a compensatory response to increased neuronal excitability within the network. Nevertheless, striking increases in pERK labeling occurred at the time of spontaneous seizures and were evident in large populations of neurons at very short intervals (as early as 2 min) after detection of a behavioral seizure. These findings suggest that increased pERK labeling could be one of the earliest immunohistochemical indicators of neurons that are activated at the time of a spontaneous seizure. PMID:18675888

  18. Electrographic seizures are significantly reduced by in vivo inhibition of neuronal uptake of extracellular glutamine in rat hippocampus

    PubMed Central

    Kanamori, Keiko; Ross, Brian D.

    2013-01-01

    Summary Rats were given unilateral kainate injection into hippocampal CA3 region, and the effect of chronic electrographic seizures on extracellular glutamine (GLNECF) was examined in those with low and steady levels of extracellular glutamate (GLUECF). GLNECF, collected by microdialysis in awake rats for 5 h, decreased to 62 ± 4.4% of the initial concentration (n = 6). This change correlated with the frequency and magnitude of seizure activity, and occurred in the ipsilateral but not in contralateral hippocampus, nor in kainate-injected rats that did not undergo seizure (n = 6). Hippocampal intracellular GLN did not differ between the Seizure and No-Seizure Groups. These results suggested an intriguing possibility that seizure-induced decrease of GLNECF reflects not decreased GLN efflux into the extracellular fluid, but increased uptake into neurons. To examine this possibility, neuronal uptake of GLNECF was inhibited in vivo by intrahippocampal perfusion of 2-(methylamino)isobutyrate, a competitive and reversible inhibitor of the sodium-coupled neutral amino acid transporter (SNAT) subtypes 1 and 2, as demonstrated by 1.8 ± 0.17 fold elevation of GLNECF (n = 7). The frequency of electrographic seizures during uptake inhibition was reduced to 35 ± 7% (n = 7) of the frequency in pre-perfusion period, and returned to 88 ± 9% in the post-perfusion period. These novel in vivo results strongly suggest that, in this well-established animal model of temporal-lobe epilepsy, the observed seizure-induced decrease of GLNECF reflects its increased uptake into neurons to sustain enhanced glutamatergic epileptiform activity, thereby demonstrating a possible new target for anti-seizure therapies. PMID:24070846

  19. Beamlet focal plane diagnostic

    SciTech Connect

    Caird, J.A.; Nielsen, N.D.; Patton, H.G.; Seppala, L.G.; Thompson, C.E.; Wegner, P.J.

    1996-12-01

    This paper describes the major optical and mechanical design features of the Beamlet Focal Plane Diagnostic system as well as measurements of the system performance, and typical data obtained to date. We also discuss the NIF requirements on the focal spot that we are interested in measuring, and some of our plans for future work using this system.

  20. Retrospective study of late febrile seizures.

    PubMed

    Webb, D W; Jones, R R; Manzur, A Y; Farrell, K

    1999-04-01

    This retrospective study documents the clinical features, electroencephalographic data, and outcome of 50 children with a history of seizures with fever that occurred after 5 years of age. Children with afebrile seizures before the onset of febrile seizures were excluded. Outcome was based on a cross-sectional survey and the follow-up period was 1-13 years. Of the 50 children, 40 had two or fewer febrile seizures after 5 years of age, and febrile seizures did not occur after 10 years of age. Twenty had complex febrile seizures, and 16 had a first-degree relative with febrile seizures. Five developed afebrile seizures, and 18 had educational difficulties. Epileptiform electroencephalographic abnormalities were observed in 22 but were not predictive of later afebrile seizures. Febrile seizures that occur after 5 years of age recur infrequently and cease by 10 years of age. The risk of developing afebrile seizures in this group is small. PMID:10328275

  1. Idiopathic focal epilepsies: the "lost tribe".

    PubMed

    Pal, Deb K; Ferrie, Colin; Addis, Laura; Akiyama, Tomoyuki; Capovilla, Giuseppe; Caraballo, Roberto; de Saint-Martin, Anne; Fejerman, Natalio; Guerrini, Renzo; Hamandi, Khalid; Helbig, Ingo; Ioannides, Andreas A; Kobayashi, Katsuhiro; Lal, Dennis; Lesca, Gaetan; Muhle, Hiltrud; Neubauer, Bernd A; Pisano, Tiziana; Rudolf, Gabrielle; Seegmuller, Caroline; Shibata, Takashi; Smith, Anna; Striano, Pasquale; Strug, Lisa J; Szepetowski, Pierre; Valeta, Thalia; Yoshinaga, Harumi; Koutroumanidis, Michalis

    2016-09-01

    The term idiopathic focal epilepsies of childhood (IFE) is not formally recognised by the ILAE in its 2010 revision (Berg et al., 2010), nor are its members and boundaries precisely delineated. The IFEs are amongst the most commonly encountered epilepsy syndromes affecting children. They are fascinating disorders that hold many "treats" for both clinicians and researchers. For example, the IFEs pose many of the most interesting questions central to epileptology: how are functional brain networks involved in the manifestation of epilepsy? What are the shared mechanisms of comorbidity between epilepsy and neurodevelopmental disorders? How do focal EEG discharges impact cognitive functioning? What explains the age-related expression of these syndromes? Why are EEG discharges and seizures so tightly locked to slow-wave sleep? In the last few decades, the clinical symptomatology and the respective courses of many IFEs have been described, although they are still not widely appreciated beyond the specialist community. Most neurologists would recognise the core syndromes of IFE to comprise: benign epilepsy of childhood with centro-temporal spikes or Rolandic epilepsy (BECTS/RE); Panayiotopoulos syndrome; and the idiopathic occipital epilepsies (Gastaut and photosensitive types). The Landau-Kleffner syndrome and the related (idiopathic) epilepsy with continuous spikes and waves in sleep (CSWS or ESES) are also often included, both as a consequence of the shared morphology of the interictal discharges and their potential evolution from core syndromes, for example, CSWS from BECTS. Atypical benign focal epilepsy of childhood also has shared electro-clinical features warranting inclusion. In addition, a number of less well-defined syndromes of IFE have been proposed, including benign childhood seizures with affective symptoms, benign childhood epilepsy with parietal spikes, benign childhood seizures with frontal or midline spikes, and benign focal seizures of adolescence. The

  2. [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. PMID:25585440

  3. Seizures of idiopathic generalized epilepsies.

    PubMed

    Durón, Reyna M; Medina, Marco T; Martínez-Juárez, Iris E; Bailey, Julia N; Perez-Gosiengfiao, Katerina Tanya; Ramos-Ramírez, Ricardo; López-Ruiz, Minerva; Alonso, María Elisa; Ortega, Ramón H Castro; Pascual-Castroviejo, Ignacio; Machado-Salas, Jesús; Mija, Lizardo; Delgado-Escueta, Antonio V

    2005-01-01

    Idiopathic generalized epilepsies (IGEs) comprise at least 40% of epilepsies in the United States, 20% in Mexico, and 8% in Central America. Here, we review seizure phenotypes across IGE syndromes, their response to treatment and advances in molecular genetics that influence nosology. Our review included the Medline database from 1945 to 2005 and our prospectively collected Genetic Epilepsy Studies (GENESS) Consortium database. Generalized seizures occur with different and similar semiologies, frequencies, and patterns, ages at onset, and outcomes in different IGEs, suggesting common neuroanatomical pathways for seizure phenotypes. However, the same seizure phenotypes respond differently to the same treatments in different IGEs, suggesting different molecular defects across syndromes. De novo mutations in SCN1A in sporadic Dravet syndrome and germline mutations in SCN1A, SCN1B, and SCN2A in generalized epilepsies with febrile seizures plus have unraveled the heterogenous myoclonic epilepsies of infancy and early childhood. Mutations in GABRA1, GABRG2, and GABRB3 are associated with absence seizures, while mutations in CLCN2 and myoclonin/EFHC1 substantiate juvenile myoclonic epilepsy as a clinical entity. Refined understanding of seizure phenotypes, their semiology, frequencies, and patterns together with the identification of molecular lesions in IGEs continue to accelerate the development of molecular epileptology. PMID:16302874

  4. Migrating partial seizures in infancy: a malignant disorder with developmental arrest.

    PubMed

    Coppola, G; Plouin, P; Chiron, C; Robain, O; Dulac, O

    1995-10-01

    Fourteen infants of both sexes had a previously unreported epileptic condition characterized by nearly continuous multifocal seizures. The first seizures occurred at a mean age of 3 months, without antecedent risk factors. At 1 to 10 months, the seizures became very frequent. They were partial with variable clinical expression, and the EEG showed that the discharges randomly involved multiple independent sites, moving from one cortical area to another in consecutive seizures. Although their topography varied, the EEG ictal pattern of each seizure was very similar. It consisted of rhythmic alpha or theta activity which spread to involve an increasing area of the cortical surface. Patients regressed developmentally and became quadriplegic with severe axial hypotonia. Three patients died at age 7 months and at age 7 and 8 years, respectively. Seizures were controlled in only 2 patients, and only 3 children resumed psychomotor development. Extensive investigation failed to determine an etiology, and there was no familial recurrence. Neuropathological examination of the brain in two cases showed only severe hippocampal neuronal loss and accompanying gliosis. PMID:7555952

  5. Magnetic resonance imaging findings in children with a first recognized seizure.

    PubMed

    Kalnin, Andrew J; Fastenau, Philip S; deGrauw, Ton J; Musick, Beverly S; Perkins, Susan M; Johnson, Cynthia S; Mathews, Vincent P; Egelhoff, John C; Dunn, David W; Austin, Joan K

    2008-12-01

    This study characterized structural abnormalities associated with onset of seizures in children, using magnetic resonance imaging and a standardized classification system in a large prospective cohort. Two hundred eighty-one children aged 6-14 years completed magnetic resonance imaging within 6 months of their first recognized seizure. Most examinations were performed with a standardized, dedicated seizure protocol; all were scored using a standard scoring system. At least one magnetic resonance imaging abnormality was identified in 87 of 281 (31%) children with a first recognized seizure. Two or more abnormalities were identified in 34 (12%). The commonest abnormalities were ventricular enlargement (51%), leukomalacia/gliosis (23%), gray-matter lesions such as heterotopias and cortical dysplasia (12%), volume loss (12%), other white-matter lesions (9%), and encephalomalacia (6%). Abnormalities defined as significant, or potentially related to seizures, occurred in 40 (14%). Temporal lobe and hippocampal abnormalities were detected at a higher frequency than in previous studies (13/87). Magnetic resonance imaging and a standardized, reliable, valid scoring system demonstrated a higher rate of abnormal findings than previously reported, including findings formerly considered incidental. Practice parameters may need revision, to expand the definition of significant abnormalities and support wider use of magnetic resonance imaging in children with newly diagnosed seizures. PMID:19027586

  6. Seizure-Induced Oxidative Stress in Temporal Lobe Epilepsy

    PubMed Central

    2015-01-01

    An insult to the brain (such as the first seizure) causes excitotoxicity, neuroinflammation, and production of reactive oxygen/nitrogen species (ROS/RNS). ROS and RNS produced during status epilepticus (SE) overwhelm the mitochondrial natural antioxidant defense mechanism. This leads to mitochondrial dysfunction and damage to the mitochondrial DNA. This in turn affects synthesis of various enzyme complexes that are involved in electron transport chain. Resultant effects that occur during epileptogenesis include lipid peroxidation, reactive gliosis, hippocampal neurodegeneration, reorganization of neural networks, and hypersynchronicity. These factors predispose the brain to spontaneous recurrent seizures (SRS), which ultimately establish into temporal lobe epilepsy (TLE). This review discusses some of these issues. Though antiepileptic drugs (AEDs) are beneficial to control/suppress seizures, their long term usage has been shown to increase ROS/RNS in animal models and human patients. In established TLE, ROS/RNS are shown to be harmful as they can increase the susceptibility to SRS. Further, in this paper, we review briefly the data from animal models and human TLE patients on the adverse effects of antiepileptic medications and the plausible ameliorating effects of antioxidants as an adjunct therapy. PMID:25650148

  7. Electroencephalographic seizures during cardiopulmonary bypass

    PubMed Central

    Stockard, J.; Calanchini, P.; Bickford, R.; Billinger, T.

    1974-01-01

    Eleven cardiac operations are reported in which there was electroencephalographic and/or clinical evidence of seizure activity during cardiopulmonary bypass (CPB). In four patients seizure activity appeared after acute episodes of cerebral ischaemia resulting from either hypotension or pump-generated emboli occurring at the beginning of CPB, or from air embolism occurring at the end of CPB when the myocardium was closed and defibrillated. In the remaining seven patients the seizures appeared to result from the synergistic action of a toxic substance in the perfusate with pre-existing or CPB-induced alterations in cerebral physiology. Images PMID:4819907

  8. Optical triggered seizures using a caged 4-Aminopyridine

    PubMed Central

    Zhao, Mingrui; McGarry, Laura M.; Ma, Hongtao; Harris, Samuel; Berwick, Jason; Yuste, Rafael; Schwartz, Theodore H.

    2015-01-01

    Animal models of epilepsy are critical not only for understanding the fundamental mechanism of epilepsy but also for testing the efficacy of new antiepileptic drugs and novel therapeutic interventions. Photorelease of caged molecules is widely used in biological research to control pharmacologic events with high spatio-temporal resolution. We developed a technique for in vivo optical triggering of neocortical seizures using a novel caged compound based on ruthenium photochemistry (RuBi-4AP). Epileptiform events in mouse cortex were induced with blue light in both whole brain and focal illumination. Multi-electrode array recording and optical techniques were used to characterize the propagation of these epileptic events, including interictal spikes, polyspikes, and ictal discharges. These results demonstrate a novel optically-triggered seizure model, with high spatio-temporal control, that could have widespread application in the investigation of ictal onset, propagation and to develop novel light-based therapeutic interventions. PMID:25698919

  9. Effects of neonatal hypoxic-ischemic episodes on late seizure outcomes in C57 black mice.

    PubMed

    Peng, Jessie; Li, Ran; Arora, Neha; Lau, Marcus; Lim, Stellar; Wu, Chiping; Eubanks, James H; Zhang, Liang

    2015-03-01

    We examined brain injury and seizures in adult C57 black mice (C57/BL6) that underwent neonatal hypoxic-ischemic (HI) episodes. Mouse pups of 7 days-old underwent a ligation of the right common carotid artery and a subsequent hypoxic challenge (8% O2 for 45min). Post-HI mice were implanted with intracranial electrodes at 2-3 months of age, subjected to behavioral/EEG recordings and hippocampal electrical stimulation in next several months and then euthanized for brain histological assessments at ages of 11-12 months. Histological assessment revealed ipsilateral brain infarctions in 9 post-HI animals. Evident motor seizures were found to occur in only 2 animals with histologically identified cystic infarctions but not in the 21 post-HI animals with or without infarctions. In response to the hippocampal stimulation, post-HI animals were less prone than sham controls to evoked motor seizures. We thus suggest that adult C57 black mice may have low propensity of developing epileptic seizures following the neonatal HI episode. Our present observations may be relevant to future investigation of post-HI epileptogenesis in mouse models. PMID:25769378

  10. Chronic stress shifts the GABA reversal potential in the hippocampus and increases seizure susceptibility.

    PubMed

    MacKenzie, Georgina; Maguire, Jamie

    2015-01-01

    The most commonly reported precipitating factor for seizures is stress. However, the underlying mechanisms whereby stress triggers seizures are not yet fully understood. Here we demonstrate a potential mechanism underlying changes in neuronal excitability in the hippocampus following chronic stress, involving a shift in the reversal potential for GABA (EGABA) associated with a dephosphorylation of the potassium chloride co-transporter, KCC2. Mice subjected to chronic restraint stress (30min/day for 14 consecutive days) exhibit an increase in serum corticosterone levels which is associated with increased susceptibility to seizures induced with kainic acid (20mg/kg). Following chronic stress, but not acute stress, we observe a dephosphorylation of KCC2 residue S940, which regulates KCC2 cell surface expression and function, in the hippocampus. To determine the impact of alterations in KCC2 expression following chronic stress, we performed gramicidin perforated patch recordings to measure changes in EGABA and neuronal excitability of principal hippocampal neurons. We observe a depolarizing shift in EGABA in hippocampal CA1 pyramidal neurons after chronic stress. In addition, there is an increase in the intrinsic excitability of CA1 pyramidal neurons, evident by a shift in the input-output curve which could be reversed with the NKCC1 inhibitor, bumetanide. These data uncover a potential mechanism involving chronic stress-induced plasticity in chloride homeostasis which may contribute to stress-induced seizure susceptibility. PMID:25524838