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Sample records for focal hippocampal seizures

  1. Remote effects of focal hippocampal seizures on the rat neocortex

    PubMed Central

    Englot, Dario J.; Mishra, Asht M.; Mansuripur, Peter K.; Herman, Peter; Hyder, Fahmeed; Blumenfeld, Hal

    2008-01-01

    Seizures have both local and remote effects on nervous system function. While propagated seizures are known to disrupt cerebral activity, little work has been done on remote network effects of seizures that do not propagate. Human focal temporal lobe seizures demonstrate remote changes including slow waves on electroencephalography (EEG) and decreased cerebral blood flow (CBF) in the neocortex. Ictal neocortical slow waves have been interpreted as seizure propagation, however we hypothesize that they reflect a depressed cortical state resembling sleep or coma. To investigate this hypothesis, we performed multi-modal studies of partial and secondarily-generalized limbic seizures in rats. Video/EEG monitoring of spontaneous seizures revealed slow waves in the frontal cortex during behaviorally mild partial seizures, contrasted with fast poly-spike activity during convulsive generalized seizures. Seizures induced by hippocampal stimulation produced a similar pattern, and were used to perform functional magnetic resonance imaging (fMRI) weighted for blood oxygenation (BOLD) and blood volume (CBV), demonstrating increased signals in hippocampus, thalamus and septum, but decreases in orbitofrontal, cingulate, and retrosplenial cortex during partial seizures; and increases in all these regions during propagated seizures. Combining these results with neuronal recordings and CBF measurements, we related neocortical slow waves to reduced neuronal activity and cerebral metabolism during partial seizures, but found increased neuronal activity and metabolism during propagated seizures. These findings suggest that ictal neocortical slow waves represent an altered cortical state of depressed function, not propagated seizure activity. This remote effect of partial seizures may cause impaired cerebral functions, including loss of consciousness. PMID:18768701

  2. Partial (focal) seizure

    MedlinePlus

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

  3. TONIC INFLUENCE OF NEOCORTEX ON HIPPOCAMPAL SEIZURES.

    PubMed

    Saralidze, E; Khuchua, L; Kobaidze, I

    2016-09-01

    The interaction between different brain structures could be crucial to predicting seizure occurrence, threshold and spread. Moreover, the sleep-wake cycle and electrical activity of brain structures in different phases of sleep could significantly affect the pattern and extent of seizure spread, and therefore the characteristics of epileptic activity. In this animal model using 15 Wistar rats, we show that the duration of hippocampal seizures, induced by electrical stimulation of the hippocampus, is significantly increased during slow sleep. Moreover, decreasing the electrical activity of the neocortex by cooling of the cortical surface or induction of cortical spreading depression also caused an increase in hippocampal seizure duration. Conversely, warming the cortical surface triggered a remission in spreading depression, in turn restoring the duration of epileptic episodes. Our data suggest that the neocortex probably exerts a tonic inhibitory influence on hippocampal seizures. Thus, cortico-hippocampal interaction could be an important component in the manifestation and generalization of limbic seizures.

  4. 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.

  5. Hippocampal sclerosis and associated focal cortical dysplasia-related epilepsy in neurofibromatosis type I.

    PubMed

    Gales, Jordan; Prayson, Richard A

    2017-03-01

    Neurofibromatosis type I (NF1) is a relatively common disorder associated with a range of neurologic sequelae. Refractory epilepsy occurs in 4-13% of NF1 patients. Hippocampal sclerosis and focal cortical dysplasia, both well-defined epilepsy-related entities, have been described in a subset of cases. To our knowledge, there has been only one other series describing coexistent focal cortical dysplasia and hippocampal sclerosis in the setting of NF1. We report two such patients who presented with intractable seizures requiring epilepsy surgery. Histologically, the hippocampal sclerosis specimen met criteria for the International League Against Epilepsy (ILAE) hippocampal sclerosis subtypes Ia and II respectively. The associated focal cortical dysplasia observed within the resected temporal lobe were both consistent with ILAE focal cortical dysplasia type IIIa (e.g. associated with a secondary lesion). Post-operatively, both patients had recurrence of habitual seizures, with one case continuing to have intractable seizures following two subsequent temporal lobectomies. Although hippocampal sclerosis association with focal cortical dysplasia is well document in epilepsy, it has been rarely described in the setting of neurofibromatosis type I. Although prior surgical series have shown good epilepsy surgery outcomes within neurofibromatosis type I, these two cases did not.

  6. Focal Seizures Induced by Intracranial Electroencephalogram Grids

    PubMed Central

    Brown, Mesha-Gay; Litt, Brian; Davis, Kathryn; Richardson, Andrew G; Lucas, Timothy

    2016-01-01

    Here we present a unique, but important seizure variant directly related to placement of subdural grids. Two distinct epileptogenic zones were identified, one which correlated with the patient’s baseline seizures and a separate zone associated with atypical semiology and localization. Inspection of this zone at surgery revealed cortical deformation from the grid itself. The patient underwent successful surgical resection of the primary epileptogenic zone, but not that of the atypical zone. She remains seizure free at two years following surgery. Recognition of grid-induced seizures is important as they may confound the interpretation of intracranial electroencephalograms (iEEG) and mislead resective surgery. PMID:27896038

  7. Olanzapine-related repetitive focal seizures with lingual dystonia.

    PubMed

    Anzellotti, Francesca; Capasso, Margherita; Frazzini, Valerio; Onofrj, Marco

    2016-03-01

    Olanzapine-related seizures have rarely been reported despite associated proconvulsant risk factors described in the literature: myoclonic status, increased frequency of seizures, tonic-clonic seizures, as well as fatal status epilepticus. We present a psychiatric patient who developed repetitive focal motor seizures and lingual dystonia when olanzapine was added for psychomotor agitation and aggressiveness. Olanzapine was immediately suspended and the seizures progressively disappeared. A control EEG showed no paroxysmal discharges. Olanzapine shares some pharmacological similarities with clozapine, a neuroleptic with a high risk of dose-dependent seizures. This adverse effect should be taken into account, and olanzapine should be used with caution if concomitant circumstances decrease the seizure threshold. [Published with video sequence online].

  8. 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

  9. Adjunctive pregabalin vs gabapentin for focal seizures

    PubMed Central

    Glue, Paul; Friedman, Daniel; Almas, Mary; Yardi, Nandan; Knapp, Lloyd; Pitman, Verne; Posner, Holly B.

    2016-01-01

    Objective: To evaluate the comparative safety and adjunctive efficacy of pregabalin and gabapentin in reducing seizure frequency in patients with partial-onset seizures based on prestudy modeling showing superior efficacy for pregabalin. Methods: The design of this comparative efficacy and safety study of pregabalin and gabapentin as adjunctive treatment in adults with refractory partial-onset seizures was randomized, flexible dose, double blind, and parallel group. The study included a 6-week baseline and a 21-week treatment phase. The primary endpoint was the percentage change from baseline in 28-day seizure rate to the treatment phase. Results: A total of 484 patients were randomized to pregabalin (n = 242) or gabapentin (n = 242). Of these, 359 patients (187 pregabalin, 172 gabapentin) completed the treatment phase. The observed median and mean in percentage change from baseline was −58.65 and −47.7 (SD 48.3) for pregabalin and −57.43 and −45.28 (SD 60.6) for gabapentin. For the primary endpoint, there was no significant difference between treatments. The Hodges-Lehman estimated median difference was 0.0 (95% confidence interval −6.0 to 7.0). Safety profiles were comparable and consistent with prior trials. Conclusions: The absence of the anticipated efficacy difference based on modeling of prior, nearly identical trials and the larger-than-expected response rates of the 2 antiepileptic drugs were unexpected. These findings raise questions that are potentially important to consider in future comparative efficacy trials. ClinicalTrials.gov identifier: NCT00537940. Classification of evidence: This study provides Class II evidence that for patients with partial seizures enrolled in this study, pregabalin is not superior to gabapentin in reducing seizure frequency. Because of the atypical response rates, the results of this study are poorly generalizable to other epilepsy populations. PMID:27521437

  10. Chemical-genetic attenuation of focal neocortical seizures.

    PubMed

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

    2014-05-27

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

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

    PubMed

    Scott, Lesley J

    2015-12-01

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

  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. Microscale Spatiotemporal Dynamics during Neocortical Propagation of Human Focal Seizures

    PubMed Central

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

    2015-01-01

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

  14. Focal epileptic seizures mimicking sleep paralysis.

    PubMed

    Galimberti, Carlo Andrea; Ossola, Maria; Colnaghi, Silvia; Arbasino, Carla

    2009-03-01

    Sleep paralysis (SP) is a common parasomnia. The diagnostic criteria for SP, as reported in the International Classification of Sleep Disorders, are essentially clinical, as electroencephalography (EEG)-polysomnography (PSG) is not mandatory. We describe a subject whose sleep-related events fulfilled the diagnostic criteria for SP, even though her visual hallucinations were elementary, repetitive and stereotyped, thus differing from those usually reported by patients with SP. Video/EEG-PSG documented the focal epileptic nature of the SP-like episodes.

  15. 24-hour rhythmicity of seizures in refractory focal epilepsy.

    PubMed

    Nzwalo, Hipólito; Menezes Cordeiro, Inês; Santos, Ana Catarina; Peralta, Rita; Paiva, Teresa; Bentes, Carla

    2016-02-01

    The occurrence of seizures in specific types of epilepsies can follow a 24-hour nonuniform or nonrandom pattern. We described the 24-hour pattern of clinical seizures in patients with focal refractory epilepsy who underwent video-electroencephalography monitoring. Only patients who were candidates for epilepsy surgery with an unequivocal seizure focus were included in the study. A total of 544 seizures from 123 consecutive patients were analyzed. Specific time of seizures were distributed along 3- or 4-hour time blocks or bins throughout the 24-hour period. The mean age of the subjects was 37.7 years, with standard deviation of 11.5 years, median of 37. The majority were females (70/56%). The majority of patients had a seizure focus located in the mesial temporal lobe (102/83%) and in the neocortical temporal lobe (13/11%). The remaining patients had a seizure focus located in the extratemporal lobe (8/6%). The most common etiology was mesial temporal sclerosis (86/69.9%). Nonuniform seizure distribution was observed in seizures arising from the temporal lobe (mesial temporal lobe and neocortical temporal lobe), with two peaks found in both 3- and 4-hour bins: 10:00-13:00/16:00-19:00 and 08:00-12:00/16:00-20:00 respectively (p=0.004). No specific 24-hour pattern was identified in seizures from extratemporal location. The 24-hour rhythmicity of seizure distribution is recognized in certain types of epilepsy, but studies on the topic are scarce. Their replication and validation is therefore needed. Our study confirms the bimodal pattern of temporal lobe epilepsy independently of the nature of the lesion. However, peak times differ between different studies, suggesting that the ambient, rhythmic exogenous factors or environmental/social zeitgebers, may modulate the 24-hour rhythmicity of seizures. Characterization of these 24-hour patterns of seizure occurrence can influence diagnosis and treatment in selected types of epilepsy, such as the case of temporal lobe

  16. Optogenetic stimulation of cholinergic brainstem neurons during focal limbic seizures: Effects on cortical physiology.

    PubMed

    Furman, Moran; Zhan, Qiong; McCafferty, Cian; Lerner, Benjamin A; Motelow, Joshua E; Meng, Jin; Ma, Chanthia; Buchanan, Gordon F; Witten, Ilana B; Deisseroth, Karl; Cardin, Jessica A; Blumenfeld, Hal

    2015-12-01

    Focal temporal lobe seizures often cause impaired cortical function and loss of consciousness. Recent work suggests that the mechanism for depressed cortical function during focal seizures may depend on decreased subcortical cholinergic arousal, which leads to a sleep-like state of cortical slow-wave activity. To test this hypothesis, we sought to directly activate subcortical cholinergic neurons during focal limbic seizures to determine the effects on cortical function. Here we used an optogenetic approach to selectively stimulate cholinergic brainstem neurons in the pedunculopontine tegmental nucleus during focal limbic seizures induced in a lightly anesthetized rat model. We found an increase in cortical gamma activity and a decrease in delta activity in response to cholinergic stimulation. These findings support the mechanistic role of reduced subcortical cholinergic arousal in causing cortical dysfunction during seizures. Through further work, electrical or optogenetic stimulation of subcortical arousal networks may ultimately lead to new treatments aimed at preventing cortical dysfunction during seizures.

  17. 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

  18. 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

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

    PubMed

    Caraballo, Roberto; Noli, Daniel; Cachia, Pedro

    2015-06-01

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

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

    NASA Astrophysics Data System (ADS)

    Takeshita, Daisuke; Bahar, Sonya

    2011-12-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2014-04-01

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

  3. Restoring Conscious Arousal During Focal Limbic Seizures with Deep Brain Stimulation.

    PubMed

    Kundishora, Adam J; Gummadavelli, Abhijeet; Ma, Chanthia; Liu, Mengran; McCafferty, Cian; Schiff, Nicholas D; Willie, Jon T; Gross, Robert E; Gerrard, Jason; Blumenfeld, Hal

    2016-03-03

    Impaired consciousness occurs suddenly and unpredictably in people with epilepsy, markedly worsening quality of life and increasing risk of mortality. Focal seizures with impaired consciousness are the most common form of epilepsy and are refractory to all current medical and surgical therapies in about one-sixth of cases. Restoring consciousness during and following seizures would be potentially transformative for these individuals. Here, we investigate deep brain stimulation to improve level of conscious arousal in a rat model of focal limbic seizures. We found that dual-site stimulation of the central lateral nucleus of the intralaminar thalamus (CL) and the pontine nucleus oralis (PnO) bilaterally during focal limbic seizures restored normal-appearing cortical electrophysiology and markedly improved behavioral arousal. In contrast, single-site bilateral stimulation of CL or PnO alone was insufficient to achieve the same result. These findings support the "network inhibition hypothesis" that focal limbic seizures impair consciousness through widespread inhibition of subcortical arousal. Driving subcortical arousal function would be a novel therapeutic approach to some forms of refractory epilepsy and may be compatible with devices already in use for responsive neurostimulation. Multisite deep brain stimulation of subcortical arousal structures may benefit not only patients with epilepsy but also those with other disorders of consciousness.

  4. The Control of Seizure-Like Activity in the Rat Hippocampal Slice

    PubMed Central

    Khosravani, Houman; Carlen, Peter L.; Velazquez, Jose L. Perez

    2003-01-01

    The sudden and transient hypersynchrony of neuronal firing that characterizes epileptic seizures can be considered as the transitory stabilization of metastable states present within the dynamical repertoire of a neuronal network. Using an in vitro model of recurrent spontaneous seizures in the rat horizontal hippocampal slice preparation, we present an approach to characterize the dynamics of the transition to seizure, and to use this information to control the activity and avoid the occurrence of seizure-like events. The transition from the interictal activity (between seizures) to the seizure-like event is aborted by brief (20–50 s) low-frequency (0.5 Hz) periodic forcing perturbations, applied via an extracellular stimulating electrode to the mossy fibers, the axons of the dentate neurons that synapse onto the CA3 pyramidal cells. This perturbation results in the stabilization of an interictal-like low-frequency firing pattern in the hippocampal slice. The results derived from this work shed light on the dynamics of the transition to seizure and will further the development of algorithms that can be used in automated devices to stop seizure occurrence. PMID:12524321

  5. Nonprogressive familial leukoencephalopathy with porencephalic cyst and focal seizures.

    PubMed

    Blumkin, Lubov; Watemberg, Nathan; Lev, Dorit; Malinger, Gustavo; Luckman, Yehudit; Ben-Zeev, Bruria; Lerman-Sagie, Tally

    2006-02-01

    Two siblings with a similar white-matter disease but different clinical symptoms are described. The first sibling suffers from nonprogressive spastic hemiparesis secondary to a congenital periventricular porencephalic cyst. Her brother has focal epilepsy. On magnetic resonance imaging, both patients show diffuse white-matter involvement predominantly of the posterior periventricular area. We suggest that this is a familial white-matter disorder with minimal symptoms and no progression in early childhood.

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

    PubMed Central

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

    2012-01-01

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

  7. Seizures in early life suppress hippocampal dendrite growth while impairing spatial learning.

    PubMed

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

    2011-11-01

    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 44days 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 littermate 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.

  8. FOCAL GENERATION OF PAROXYSMAL FAST RUNS DURING ELECTROGRAPHIC SEIZURES

    PubMed Central

    Boucetta, Sofiane; Chauvette, Sylvain; Bazhenov, Maxim; Timofeev, Igor

    2008-01-01

    Purpose A cortically generated Lennox-Gastaut type seizure is associated with spike-wave/polyspike-wave discharges at 1.0–2.5 Hz and fast runs at 7–16 Hz. Here we studied the patterns of synchronization during runs of paroxysmal fast spikes. Methods Electrographic activities were recorded using multisite intracellular and field potential recordings in vivo from cats anesthetized with ketamine-xylazine. In different experiments, the recording electrodes were located either at short distances (<1 mm) or at longer distances (up to 12 mm). The main experimental findings were tested in computational models. Results In the majority of cases, the onset and the offset of fast runs occurred almost simultaneously in different recording sites. The amplitude and duration of fast runs could vary by orders of magnitude. Within the fast runs, the patterns of synchronization recorded in different electrodes were as following: (i) synchronous, in phase, (ii) synchronous, with phase shift, (iii) patchy, repeated in phase/phase shift transitions and (iv) non-synchronous, slightly different frequencies in different recording sites or absence of oscillatory activity in one of the recording sites; the synchronous patterns (in phase or with phase shifts) were most common. All these patterns could be recorded in the same pair of electrodes during different seizures and they were reproduced in a computational network model. Intrinsically-bursting (IB) neurons fired more spikes per cycle than any other neurons suggesting their leading role in the fast run generation. Conclusions Once started, the fast runs are generated locally with variable correlations between neighboring cortical foci. PMID:18616553

  9. Critical evaluation of four different seizure detection systems tested on one patient with focal and generalized tonic and clonic seizures.

    PubMed

    Van de Vel, Anouk; Verhaert, Kristien; Ceulemans, Berten

    2014-08-01

    For long-term home monitoring of epileptic seizures, the measurement of extracerebral body signals such as abnormal movement is often easier and less obtrusive than monitoring intracerebral brain waves with electroencephalography (EEG). Non-EEG devices are commercially available but with little scientifically valid information and no consensus on which system works for which seizure type or patient. We evaluated four systems based on efficiency, comfort, and user-friendliness and compared them in one patient suffering from focal epilepsy with secondary generalization. The Emfit mat, Epi-Care device, and Epi-Care Free bracelet are commercially available alarm systems, while the VARIA (Video, Accelerometry, and Radar-Induced Activity recording) device is being developed by our team and requires offline analysis for seizure detection and does so by presenting the 5% or 10% (patient-specific) most abnormal movement events, irrespective of the number of seizures per night. As we chose to mimic the home situation, we did not record EEG and compared our results to the seizures reported by experienced staff that were monitoring the patient on a semicontinuous basis. This resulted in a sensitivity (sens) of 78% and false detection rate (FDR) of 0.55 per night for Emfit, sens 40% and FDR 0.41 for Epi-Care, sens 41% and FDR 0.05 for Epi-Care Free, and sens 56% and FDR 20.33 for VARIA. Good results were obtained by some of the devices, even though, as expected, nongeneralized and nonrhythmic motor seizures (involving the head only, having a tonic phase, or manifesting mainly as sound) were often missed. The Emfit mat was chosen for our patient, also based on user-friendliness (few setup steps), comfort (contactless), and possibility to adjust patient-specific settings. When in need of a seizure detection system for a patient, a thorough individual search is still required, which suggests the need for a database or overview including results of clinical trials describing the

  10. 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

  11. Mossy Fiber Plasticity and Enhanced Hippocampal Excitability, Without Hippocampal Cell Loss or Altered Neurogenesis, in an Animal Model of Prolonged Febrile Seizures

    PubMed Central

    Bender, Roland A.; Dubé, Celine; Gonzalez-Vega, Rebeca; Mina, Erene W.; Baram, Tallie Z.

    2010-01-01

    Seizures induced by fever (febrile seizures) are the most frequent seizures affecting infants and children; however, their impact on the developing hippocampal formation is not completely understood. Such understanding is highly important because of the potential relationship of prolonged febrile seizures to temporal lobe epilepsy. Using an immature rat model, we have previously demonstrated that prolonged experimental febrile seizures render the hippocampus hyperexcitable throughout life. Here we examined whether (1) neuronal loss, (2) altered neurogenesis, or (3) mossy fiber sprouting, all implicated in epileptogenesis in both animal models and humans, were involved in the generation of a pro-epileptic, hyperexcitable hippocampus by these seizures. The results demonstrated that prolonged experimental febrile seizures did not result in appreciable loss of any vulnerable hippocampal cell population, though causing strikingly enhanced sensitivity to hippocampal excitants later in life. In addition, experimental febrile seizures on postnatal day 10 did not enhance proliferation of granule cells, whereas seizures generated by kainic acid during the same developmental age increased neurogenesis in the immature hippocampus. However, prolonged febrile seizures resulted in long-term axonal reorganization in the immature hippocampal formation: Mossy fiber densities in granule cell- and molecular layers were significantly increased by 3 months (but not 10 days) after the seizures. Thus, the data indicate that prolonged febrile seizures influence connectivity of the immature hippocampus long-term, and this process requires neither significant neuronal loss nor altered neurogenesis. In addition, the temporal course of the augmented mossy fiber invasion of the granule cell and molecular layers suggests that it is a consequence, rather than the cause, of the hyperexcitable hippocampal network resulting from these seizures. PMID:12722980

  12. Review of therapeutic options for adjuvant treatment of focal seizures in epilepsy: focus on lacosamide.

    PubMed

    Becerra, Juan Luis; Ojeda, Joaquín; Corredera, Enrique; Ruiz Giménez, Jesús

    2011-12-05

    Epilepsy is one of the most common serious neurological conditions worldwide, with an age-adjusted incidence of approximately 50 per 100,000 persons per year in developed countries. Antiepileptic therapy can result in long-term remission in 60-70% of patients, but many patients will require combination treatment to achieve optimal seizure control, as monotherapy is ineffective at controlling seizures in 30-53% of patients. Despite the increase in available treatment options, patient outcomes have not improved significantly and there is still a need for more effective therapies. Drugs used in the treatment of focal-onset seizures are a diverse range of compounds, and in most cases their mechanism of action is unknown or poorly defined. This review discusses the efficacy and safety of the newer adjuvant antiepileptic therapies that may improve outcomes in patients unresponsive to monotherapy, including clobazam, vigabatrin, lamotrigine, gabapentin, topiramate, tiagabine, levetiracetam, oxcarbazepine, pregabalin, zonisamide and eslicarbazepine, with focus on lacosamide. Lacosamide has been shown to exert its anticonvulsant effects predominantly by enhancement of the slow inactivation of voltage-gated sodium channels. Lacosamide is indicated for use as adjuvant treatment of focal-onset seizures in patients with epilepsy, and there is some evidence that it may also be of use in patients with status epilepticus and cancer patients with epilepsy. The efficacy of lacosamide has been assessed in three randomized, double-blind, placebo-controlled clinical trials, all of which have shown lacosamide to be effective at reducing seizure frequency and increasing 50% responder rates in patients with focal-onset seizures. Long-term lacosamide treatment is generally well tolerated and is not associated with significant drug interactions; the availability of an intravenous form of the drug also makes it particularly useful for a broad range of patients.

  13. [Clinical features and gene mutations in epilepsy of infancy with migrating focal seizures].

    PubMed

    Shang, K W; Zhang, Y H; Yang, X L; Liu, A J; Yang, Z X; Liu, X Y; Jiang, Y W; Wu, X R

    2016-10-02

    Objective: To summarize the clinical features and gene mutations of epilepsy of infancy with migrating focal seizures (EIMFS). Method: Clinical features and electroencephalograms(EEG)of 9 patients with EIMFS of Peking University First Hospital from May 2015 to January 2016 were analyzed. Candidate gene mutations were screened by next generation sequencing. Result: Among the 9 patients, 3 were males and 6 were females. Two patients had family history. Seizure onset age was 2 days to 3 months after birth (median age 35 days). Migrating focal seizure was presented. Seizures manifested as eyes and(or)head deviation, involuntary blinking, swallowing, trembling or stiffness of limbs, hand clenching, flushing and cyanosis of lips, etc. Four patients had a history of status epilepticus. All 9 patients had psychomotor delay. EEG of all patients presented relatively slow background; during interictal phase, there were multi-focal epileptic discharges, which dominated one hemisphere or brain region; seizures were recorded in all 9 cases, which manifested eyes or(and)head deviation, stiffening or trembling of limbs, lip smacking, etc. Corresponding EEG showed low-medium-amplitude fast waves that originated from some brain regions and migrated to other regions. Cranial magnetic resonance imaging (MRI) was abnormal in 4 cases, which predominantly showed white matter dysplasia and enlargement of subarachnoid spaces. Two cases carried heterozygous missense mutations of SCN1A gene, while 3 cases carried heterozygous missense mutations of KCNT1 gene, all of which were de novo. One case carried compound heterozygous mutation of TBC1D24 gene(p.Gln207*, p. Ala289Va). Gene mutation was not found in 3 cases. All patients used multiple antiepileptic drugs (AED) and their seizures were not controlled. Follow-up ranged from 2 months to 5 years and 8 months, during which 4 were found dead. Two were lost to follow-up. Conclusion: EIMFS is clinically characterized by early onset, which is

  14. Seizures induce proliferation and dispersion of doublecortin-positive hippocampal progenitor cells.

    PubMed

    Jessberger, Sebastian; Römer, Benedikt; Babu, Harish; Kempermann, Gerd

    2005-12-01

    One neuropathological hallmark of temporal lobe epilepsy is granule cell dispersion, a widening of the hippocampal granule cell layer (GCL) with abnormally positioned excitatory neurons. The finding that seizure activity also induces adult hippocampal neurogenesis was taken largely as indicative of a regenerative attempt, not as part of the pathology. The aim of our study was to characterize a potential relationship between granule cell dispersion and seizure-induced neurogenesis. Kainic acid (KA)-induced seizures in mice led to increased cell proliferation and new neurons persisted for months after the seizures. We show that the proliferative stimulus did not affect nestin-expressing early precursor cells that primarily respond to physiologic mitogenic stimuli, but stimulated the division of late type-3 progenitor cells, which express doublecortin (DCX), a protein associated with cell migration. This delayed proliferation presumably interfered with migration, leading to a significant dispersion of DCX-positive progenitors and early postmitotic neurons within the dentate gyrus granule cell layer. We propose that initial seizures induce ectopic precursor cell proliferation resulting in the dispersion of immature neurons within the adult granule cell layer. Thus, seizure-generated neurons might contribute to the disease process of epilepsy.

  15. Developmental Febrile Seizures Modulate Hippocampal Gene Expression of Hyperpolarization-Activated Channels in an Isoform- and Cell-Specific Manner

    PubMed Central

    Brewster, Amy; Bender, Roland A.; Chen, Yuncai; Dube, Celine; Eghbal-Ahmadi, Mariam; Baram, Tallie Z.

    2012-01-01

    Febrile seizures, in addition to being the most common seizure type of the developing human, may contribute to the generation of subsequent limbic epilepsy. Our previous work has demonstrated that prolonged experimental febrile seizures in the immature rat model increased hippocampal excitability long term, enhancing susceptibility to future seizures. The mechanisms for these profound proepileptogenic changes did not require cell death and were associated with long-term slowed kinetics of the hyperpolarization-activated depolarizing current (IH). Here we show that these seizures modulate the expression of genes encoding this current, the hyperpolarization-activated, cyclic nucleotide-gated channels (HCNs): In CA1 neurons expressing multiple HCN isoforms, the seizures induced a coordinated reduction of HCN1 mRNA and enhancement of HCN2 expression, thus altering the neuronal HCN phenotype. The seizure-induced augmentation of HCN2 expression involved CA3 in addition to CA1, whereas for HCN4, mRNA expression was not changed by the seizures in either hippocampal region. This isoform- and region-specific transcriptional regulation of the HCNs required neuronal activity rather than hyperthermia alone, correlated with seizure duration, and favored the formation of slow-kinetics HCN2-encoded channels. In summary, these data demonstrate a novel, activity-dependent transcriptional regulation of HCN molecules by developmental seizures. These changes result in long-lasting alteration of the HCN phenotype of specific hippocampal neuronal populations, with profound consequences on the excitability of the hippocampal network. PMID:12040066

  16. Developmental febrile seizures modulate hippocampal gene expression of hyperpolarization-activated channels in an isoform- and cell-specific manner.

    PubMed

    Brewster, Amy; Bender, Roland A; Chen, Yuncai; Dube, Celine; Eghbal-Ahmadi, Mariam; Baram, Tallie Z

    2002-06-01

    Febrile seizures, in addition to being the most common seizure type of the developing human, may contribute to the generation of subsequent limbic epilepsy. Our previous work has demonstrated that prolonged experimental febrile seizures in the immature rat model increased hippocampal excitability long term, enhancing susceptibility to future seizures. The mechanisms for these profound proepileptogenic changes did not require cell death and were associated with long-term slowed kinetics of the hyperpolarization-activated depolarizing current (I(H)). Here we show that these seizures modulate the expression of genes encoding this current, the hyperpolarization-activated, cyclic nucleotide-gated channels (HCNs): In CA1 neurons expressing multiple HCN isoforms, the seizures induced a coordinated reduction of HCN1 mRNA and enhancement of HCN2 expression, thus altering the neuronal HCN phenotype. The seizure-induced augmentation of HCN2 expression involved CA3 in addition to CA1, whereas for HCN4, mRNA expression was not changed by the seizures in either hippocampal region. This isoform- and region-specific transcriptional regulation of the HCNs required neuronal activity rather than hyperthermia alone, correlated with seizure duration, and favored the formation of slow-kinetics HCN2-encoded channels. In summary, these data demonstrate a novel, activity-dependent transcriptional regulation of HCN molecules by developmental seizures. These changes result in long-lasting alteration of the HCN phenotype of specific hippocampal neuronal populations, with profound consequences on the excitability of the hippocampal network.

  17. 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

  18. 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.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Toyoda, Izumi; Fujita, Satoshi; Thamattoor, Ajoy K; Buckmaster, Paul S

    2015-04-22

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

  1. A novel KCNT1 mutation in a Japanese patient with epilepsy of infancy with migrating focal seizures.

    PubMed

    Shimada, Shino; Hirano, Yoshiko; Ito, Susumu; Oguni, Hirokazu; Nagata, Satoru; Shimojima, Keiko; Yamamoto, Toshiyuki

    2014-01-01

    Epilepsy of infancy with migrating focal seizures (EIFMS) is a rare, early-onset epileptic encephalopathy characterized by polymorphous focal seizures. De novo mutations of KCNT1 have been identified in cases of this disorder. We encountered a sporadic patient with EIFMS, who suffered tonic convulsions at the age of 9 days. Using Sanger sequencing, we identified a de novo missense mutation of the same amino acid affected by a previously identified mutation, c.1420C>T (p.Arg474Cys).

  2. Rapid eye movement sleep and hippocampal theta oscillations precede seizure onset in the tetanus toxin model of temporal lobe epilepsy.

    PubMed

    Sedigh-Sarvestani, Madineh; Thuku, Godfrey I; Sunderam, Sridhar; Parkar, Anjum; Weinstein, Steven L; Schiff, Steven J; Gluckman, Bruce J

    2014-01-22

    Improved understanding of the interaction between state of vigilance (SOV) and seizure onset has therapeutic potential. Six rats received injections of tetanus toxin (TeTX) in the ventral hippocampus that resulted in chronic spontaneous seizures. The distribution of SOV before 486 seizures was analyzed for a total of 19 d of recording. Rapid eye movement sleep (REM) and exploratory wake, both of which express prominent hippocampal theta rhythm, preceded 47 and 34%, for a total of 81%, of all seizures. Nonrapid eye movement sleep (NREM) and nonexploratory wake, neither of which expresses prominent theta, preceded 6.8 and 13% of seizures. We demonstrate that identification of SOV yields significant differentiation of seizure susceptibilities, with the instantaneous seizure rate during REM nearly 10 times higher than baseline and the rate for NREM less than half of baseline. Survival analysis indicated a shorter duration of preseizure REM bouts, with a maximum transition to seizure at ∼90 s after the onset of REM. This study provides the first analysis of a correlation between SOV and seizure onset in the TeTX model of temporal lobe epilepsy, as well as the first demonstration that hippocampal theta rhythms associated with natural behavioral states can serve a seizure-promoting role. Our findings are in contrast with previous studies suggesting that the correlations between SOV and seizures are primarily governed by circadian oscillations and the notion that hippocampal theta rhythms inhibit seizures. The documentation of significant SOV-dependent seizure susceptibilities indicates the potential utility of SOV and its time course in seizure prediction and control.

  3. Low Frequency Stimulation of Hippocampal Commissures Reduces Seizures in Chronic Rat Model of Temporal Lobe Epilepsy

    PubMed Central

    Rashid, Saifur; Pho, Gerald; Czigler, Michael; Werz, Mary Ann; Durand, Dominique M.

    2013-01-01

    SUMMARY Purpose To investigate the effects of low frequency stimulation (LFS) of a fiber track for the suppression of spontaneous seizures described by Nissinen in a rat model of human temporal lobe epilepsy. Methods Stimulation electrodes were implanted into the ventral hippocampal commissure (VHC) in a rat post-status epilepticus (SE) model of human temporal lobe epilepsy (n = 7). Two recordings electrodes were placed in the CA3 regions bilaterally and neural data was recorded for a minimum of six weeks. LFS (60 minute train of 1Hz biphasic square wave pulses, each 0.1ms in duration and 200μA in amplitude, followed by 15 minutes of rest) was applied to the VHC for, two weeks, 24 hours a day. Key Findings The baseline mean seizure frequency of the study animals was 3.7 seizures per day. The seizures were significantly reduced by the application of LFS in every animal (n=7). By the end of the two-week period of stimulation, there was a significant 90% (<1 seizure/day) reduction of seizure frequencies (p < 0.05) and a 57% reduction during the period following LFS (p < 0.05) when compared to baseline. LFS also resulted in a significant reduction of hippocampal interictal spike frequency (71%, p < 0.05), during two weeks LFS session. The hippocampal histological analysis showed no significant difference between rats that received LFS and SE-induction and those that had only received SE-induction. None of the animals showed any symptomatic hemorrhage, infection or complication. Significance LFS applied at a frequency of 1Hz significantly reduced both the excitability of the neural tissue as well as the seizure frequency in a rat model of human temporal lobe epilepsy. The results support the hypothesis that LFS of fiber tracts can be an effective method for the suppression of spontaneous seizures in a temporal lobe model of epilepsy in rats and could be lead to the development of the new therapeutic modality for human patients with temporal lobe epilepsy. PMID:22150779

  4. Seizures

    MedlinePlus

    ... Your 1- to 2-Year-Old First Aid: Seizures KidsHealth > For Parents > First Aid: Seizures Print A A A en español Folleto de instructiones: Convulsiones (Seizures) Although seizures can be frightening, many last only ...

  5. Somatostatin receptor subtypes 2 and 4 affect seizure susceptibility and hippocampal excitatory neurotransmission in mice.

    PubMed

    Moneta, D; Richichi, C; Aliprandi, M; Dournaud, P; Dutar, P; Billard, J M; Carlo, A S; Viollet, C; Hannon, J P; Fehlmann, D; Nunn, C; Hoyer, D; Epelbaum, J; Vezzani, A

    2002-09-01

    We have investigated the role of somatostatin receptor subtypes sst2 and sst4 in limbic seizures and glutamate-mediated neurotransmission in mouse hippocampus. As compared to wild-type littermates, homozygous mice lacking sst2 receptors showed a 52% reduction in EEG ictal activity induced by intrahippocampal injection of 30 ng kainic acid (P < 0.05). The number of behavioural tonic-clonic seizures was reduced by 50% (P < 0.01) and the time to onset of seizures was doubled on average (P < 0.05). Seizure-associated neurodegeneration was found in the injected hippocampus (CA1, CA3 and hilar interneurons) and sporadically in the ipsilateral latero-dorsal thalamus. This occurred to a similar extent in wild-type and sst2 knock-out mice. Intrahippocampal injection of three selective sst2 receptor agonists in wild-type mice (Octreotide, BIM 23120 and L-779976, 1.5-6.0 nmol) did not affect kainate seizures while the same compounds significantly reduced seizures in rats. L-803087 (5 nmol), a selective sst4 receptor agonist, doubled seizure activity in wild-type mice on average. Interestingly, this effect was blocked by 3 nmol octreotide. It was determined, in both radioligand binding and cAMP accumulation, that octreotide had no direct agonist or antagonist action at mouse sst4 receptors expressed in CCl39 cells, up to micromolar concentrations. In hippocampal slices from wild-type mice, octreotide (2 micro m) did not modify AMPA-mediated synaptic responses while facilitation occurred with L-803087 (2 micro m). Similarly to what was observed in seizures, the effect of L-803087 was reduced by octreotide. In hippocampal slices from sst2 knock-out mice, both octreotide and L-803087 were ineffective on synaptic responses. Our findings show that, unlike in rats, sst2 receptors in mice do not mediate anticonvulsant effects. Moreover, stimulation of sst4 receptors in the hippocampus of wild-type mice induced excitatory effects which appeared to depend on the presence of sst2

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

    PubMed Central

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

    2012-01-01

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

  7. Reversible cerebral vasoconstriction syndrome manifesting as focal seizures without a thunderclap headache: A pediatric case report.

    PubMed

    Kuga, Shuji; Goto, Hironori; Okanari, Kazuo; Maeda, Tomoki; Ihara, Kenji

    2016-10-01

    We report a pediatric case of reversible cerebral vasoconstriction syndrome with focal seizures without a thunderclap headache. A 7-year-old girl had a mild acute headache with nausea after swimming. She subsequently developed hemi-convulsions followed by right hemiplegia. Brain magnetic resonance angiography revealed generalized vasoconstriction of the main cerebral peripheral arteries. Her hemiplegia was spontaneously resolved within 6h. Over the next 24h she suffered from recurrent and transient headaches, which recurred on days 3 and 5. Follow-up magnetic resonance angiography on day 3 documented the multifocal narrowing of the main cerebral arteries, which was observed to have diminished at 12weeks after her initial presentation. She did not have any headaches or neurological deficits after day 5. This case indicates that reversible cerebral vasoconstriction syndrome should be considered in children with focal seizures even when they do not present with thunderclap headaches. The timely and appropriate evaluation by magnetic resonance angiography and imaging is essential for diagnosing reversible cerebral vasoconstriction syndrome.

  8. A novel KCNT1 mutation in a Japanese patient with epilepsy of infancy with migrating focal seizures

    PubMed Central

    Shimada, Shino; Hirano, Yoshiko; Ito, Susumu; Oguni, Hirokazu; Nagata, Satoru; Shimojima, Keiko; Yamamoto, Toshiyuki

    2014-01-01

    Epilepsy of infancy with migrating focal seizures (EIFMS) is a rare, early-onset epileptic encephalopathy characterized by polymorphous focal seizures. De novo mutations of KCNT1 have been identified in cases of this disorder. We encountered a sporadic patient with EIFMS, who suffered tonic convulsions at the age of 9 days. Using Sanger sequencing, we identified a de novo missense mutation of the same amino acid affected by a previously identified mutation, c.1420C>T (p.Arg474Cys). PMID:27081515

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

    PubMed Central

    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

  10. Alumina cream-induced focal motor seizures in cats: bilateral lesions of the mesencephalic reticular formation.

    PubMed

    Velasco, M; Velasco, F; Cepeda, C; Márquez, I; Estrada-Villanueva, F

    1986-06-01

    The effect of bilateral lesions of the mesencephalic reticular formation on the EEG-EMG patterns of types B and C alumina cream-induced focal motor seizures was studied in cats with chronically implanted electrode and cannula lesion systems. EEG patterns included number, amplitude, and contralateral propagation of type B spikes and occurrence and duration of type C tonic-clonic discharges. EMG patterns included changes in muscular multiple-unit activity time locked to the onset of type B spikes and to the onset and end of type C tonic-clonic EEG paroxysmal discharges. The lesions persistently blocked the orienting response to visual, auditory, and tactile stimuli to both sides in all cats and produced other neurologic symptoms partially or totally recovered in some cats. The lesions significantly increased the number, amplitude, and contralateral propagation of type B EEG spikes and the occurrence, but not the duration, of type C EEG tonic-clonic discharges. Ipsi- and contralateral adversion of the tonic phase were completely blocked and the muscular contractions of the clonic phase were reduced and delayed. These facts suggest that in intact epileptic cats, the mesencephalic reticular formation has an ascending suppressive influence on the mechanism related to EEG spike generation and precipitation of seizures but also a descending facilitatory control on the corticospinal epileptic impulses mediated through pyramidal and extrapyramidal pathways.

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

    PubMed Central

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

    2016-01-01

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

  12. 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.

  13. 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.

  14. 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

  15. Seizures

    MedlinePlus

    ... often with a loss of or change in consciousness. Seizures can be frightening, but most last only ... unusual sensations, uncontrollable muscle spasms, and loss of consciousness. Some seizures may be due to another medical ...

  16. Seizures

    MedlinePlus

    ... because of sudden, abnormal electrical activity in the brain. When people think of seizures, they often think of convulsions in which a person's body shakes rapidly and uncontrollably. Not all seizures ... part of the brain. Generalized seizures are a result of abnormal activity ...

  17. 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

  18. The medial septum mediates impairment of prepulse inhibition of acoustic startle induced by a hippocampal seizure or phencyclidine.

    PubMed

    Ma, Jingyi; Shen, Bixia; Rajakumar, N; Leung, L Stan

    2004-11-05

    The involvement of the septohippocampal system on the impaired sensorimotor gating induced by phencyclidine (PCP) or by an electrically induced hippocampal seizure was examined in behaving rats. An impaired sensorimotor gating, measured by prepulse inhibition (PPI) of the acoustic startle response, was observed following a hippocampal afterdischarge (AD) or systemic injection of PCP and was accompanied with an increase in hippocampal gamma waves (30-70 Hz). The medial septum infusion with muscimol (0.25 microg), a GABA(A) receptor agonist, 15 min prior to PCP or a hippocampal AD, prevented the impairment of sensorimotor gating and the increase in gamma waves. By itself, muscimol (0.25 microg) injection into the medial septum did not affect PPI, although it significantly suppressed spontaneous gamma waves. In order to identify subpopulations of neurons mediating the sensorimotor gating deficit and the hippocampal gamma wave increase, 0.14-0.21 microg of p75 antibody conjugated to saporin (192 IgG-saporin) was injected into the medial septum to selectively lesion the septohippocampal cholinergic neurons. Neither the PPI deficit nor the gamma wave increase induced by PCP or a hippocampal AD was affected by 192 IgG-saporin lesion of the medial septum. It is concluded that increase in neural activity in the medial septum participates in the impairment of sensorimotor gating and the increase in hippocampal gamma waves induced by PCP or a hippocampal AD. It is suggested that the GABAergic but not the cholinergic septohippocampal neurons mediate the sensorimotor gating deficit.

  19. Consecutive 15 min is necessary for focal low frequency stimulation to inhibit amygdaloid-kindling seizures in rats.

    PubMed

    Liu, Yang; Wang, Yi; Xu, Zhenghao; Xu, Cenglin; Ying, Xiaoying; Wang, Shuang; Zhang, Shihong; Xiao, Bo; Chen, Zhong

    2013-09-01

    Low-frequency stimulation (LFS) is emerging as a new option for the treatment of intractable epilepsy. The stimulation duration may influence the anti-epileptic effect of LFS but is poorly studied. The present study was designed to evaluate the anti-epileptic effect of focal LFS with different stimulation duration on amygdaloid-kindling seizures in rats. We found 15 and 30 min but not 1 or 5 min LFS delivered immediately after the kindling stimulation slowed the progression of behavioral seizure stages and reduced mean afterdischarge duration (ADD) during kindling acquisition. In fully kindled animals, 15 and 30min rather than 1 and 5 min LFS decreased the incidence of generalized seizures and the average seizure stage as well as shortened the cumulative generalized seizure duration (GSD). Meanwhile, EEG analysis showed 15 and 30 min LFS specifically lowered the power in delta band. However, if 15min LFS delivered intermittently by 5 min interval, it had no suppressing effect on kindling rat. Thus, it is likely that consecutive 15 min is necessary for LFS to inhibit amygdaloid-kindling seizures in rats, indicating the stimulation duration may be a key fact affecting the clinical effect of LFS on epilepsy.

  20. Inhibition of neuronal (type 1) nitric oxide synthase prevents hyperaemia and hippocampal lesions resulting from kainate-induced seizures.

    PubMed

    Montécot, C; Rondi-Reig, L; Springhetti, V; Seylaz, J; Pinard, E

    1998-06-01

    The possible roles for nitric oxide produced by neurons in epileptic conditions have been investigated from two different aspects: microcirculation and delayed damage. Our aim was to determine whether the selective inhibition of neuronal (type 1) nitric oxide synthase by 7-nitroindazole, during seizures induced by systemic kainate, modifies hippocampal blood flow and oxygen supply and influences the subsequent hippocampal damage. Experiments were performed in conscious Wistar rats whose electroencephalogram was recorded. 7-Nitroindazole (25 mg/kg, i.p.) or its vehicle was injected 30 min before kainate administration (10 mg/kg, i.p.) and then twice at 1-h intervals. Kainate triggered typical limbic seizures evolving into status epilepticus, identified by uninterrupted electroencephalographic spike activity. The seizures were stopped by diazepam (5 mg/kg, i.p.) after 1 h of status epilepticus. Three types of experiments were performed in vehicle- and 7-nitroindazole-treated rats. (1) Hippocampal nitric oxide synthase activity was measured under basal conditions, at 1 h after the onset of the status epilepticus and at 24 h after its termination (n = 4-6 per group). (2) Hippocampal blood flow and tissue partial pressure of oxygen were measured simultaneously by mass spectrometry for the whole duration of the experiment, while systemic variables and body temperature were monitored (n = 6 per group). (3) Hippocampal damage was revealed by Cresyl Violet staining and evaluated with a lesion score seven days after status epilepticus (n = 12 per group). Hippocampal nitric oxide synthase activity was not significantly modified during status epilepticus or the following day in vehicle-treated rats. In contrast, it was inhibited by 57% in 7-nitroindazole-treated rats, both in basal conditions and after 1 h of status epilepticus, but was not different from its basal level 24 h later. 7-Nitroindazole significantly decreased basal hippocampal blood flow and tissue partial

  1. 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.

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

    PubMed Central

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

    2009-01-01

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

  3. Aging-induced Seizure-related Changes to the Hippocampal Mossy Fiber Pathway in Forebrain Specific BDNF Overexpressing Mice

    PubMed Central

    Weidner, Kate L.; Goodman, Jeffrey H.; Chadman, Kathryn K.; McCloskey, Daniel P.

    2011-01-01

    Aging confers an increased risk for developing seizure activity, especially within brain regions that mediate learning and synaptic plasticity. Brain derived neurotrophic factor (BDNF) is a member of the neurotrophin family that has an important role in regulating growth and development of the nervous system. BDNF is upregulated after pharmacological seizure induction and this upregulation contributes to enhanced excitability of the hippocampal mossy fiber–CA3 pathway, which is accompanied by neuropeptide Y (NPY) upregulation. Mice overexpressing a BDNF transgene in forebrain neurons provide an avenue for understanding the role of neurotrophic support in the aged hippocampus. In this study BDNF transgenic (TG) mice were utilized to determine whether increased BDNF expression through genetic manipulation resulted in age-related changes in hippocampal excitability and NPY expression. Spontaneous behavioral seizures were observed in TG mice, but not WT mice, past 5 months of age and the severity of behavioral seizures increased with age. Electrophysiological investigation of hippocampal CA3 activity indicated that slices from aged TG mice (86%), but not age-matched WT mice, or young TG mice, showed epileptiform activity in response to either repeated paired pulse or high frequency (tetanic) stimulation. Electrophysiological results were supported by the observation of robust ectopic NPY immunoreactivity in hippocampal mossy fibers of most aged TG mice (57%), which was absent in age-matched WT mice and young TG mice. The results from this study indicate that forebrain restricted BDNF overexpression produces age-related changes in hyperexcitability and NPY immunoreactivity in mossy fiber–CA3 pathway. Together, these data suggest that the capability for BDNF to promote epileptogenesis is maintained, and may be enhanced, in the aging hippocampus. PMID:22396883

  4. Aging-induced Seizure-related Changes to the Hippocampal Mossy Fiber Pathway in Forebrain Specific BDNF Overexpressing Mice.

    PubMed

    Weidner, Kate L; Goodman, Jeffrey H; Chadman, Kathryn K; McCloskey, Daniel P

    2011-08-01

    Aging confers an increased risk for developing seizure activity, especially within brain regions that mediate learning and synaptic plasticity. Brain derived neurotrophic factor (BDNF) is a member of the neurotrophin family that has an important role in regulating growth and development of the nervous system. BDNF is upregulated after pharmacological seizure induction and this upregulation contributes to enhanced excitability of the hippocampal mossy fiber-CA3 pathway, which is accompanied by neuropeptide Y (NPY) upregulation. Mice overexpressing a BDNF transgene in forebrain neurons provide an avenue for understanding the role of neurotrophic support in the aged hippocampus. In this study BDNF transgenic (TG) mice were utilized to determine whether increased BDNF expression through genetic manipulation resulted in age-related changes in hippocampal excitability and NPY expression. Spontaneous behavioral seizures were observed in TG mice, but not WT mice, past 5 months of age and the severity of behavioral seizures increased with age. Electrophysiological investigation of hippocampal CA3 activity indicated that slices from aged TG mice (86%), but not age-matched WT mice, or young TG mice, showed epileptiform activity in response to either repeated paired pulse or high frequency (tetanic) stimulation. Electrophysiological results were supported by the observation of robust ectopic NPY immunoreactivity in hippocampal mossy fibers of most aged TG mice (57%), which was absent in age-matched WT mice and young TG mice. The results from this study indicate that forebrain restricted BDNF overexpression produces age-related changes in hyperexcitability and NPY immunoreactivity in mossy fiber-CA3 pathway. Together, these data suggest that the capability for BDNF to promote epileptogenesis is maintained, and may be enhanced, in the aging hippocampus.

  5. Feline hippocampal and piriform lobe necrosis as a consequence of severe cluster seizures in two cats in Finland.

    PubMed

    Fors, Sara; Van Meervenne, Sofie; Jeserevics, Janis; Rakauskas, Mindaugas; Cizinauskas, Sigitas

    2015-07-28

    Feline hippocampal and piriform lobe necrosis (FHN) has been reported from several countries worldwide and is considered an important aetiology for feline epileptic seizures. The aetiology of FHN remains unclear, however it is suspected that FHN might occur secondary to intense epileptic activity as described in humans and dogs although this has not yet been documented in cats. The purpose of our report is to describe the first cases of FHN in Finland diagnosed by magnetic resonance imaging (MRI) and histopathology. The two cases we describe had a well documented history of pre-existing seizures with normal brain MRI at the onset of cluster seizures but MRI done when the cats exhibited clinical deterioration secondary to severe seizure activity, revealed lesions in the hippocampus and piriform lobes typical of FHN. Our report confirms that feline hippocampus and piriform lobe necrosis does occur in the Finnish cat population and should therefore be considered as a differential diagnosis in cats with seizures. In addition, the presentation, clinical findings, results of MRI and/or histopathology shows that cats may develop FHN secondary to severe seizure activity.

  6. Altered glutamate metabolism contributes to antiepileptogenic effects in the progression from focal seizure to generalized seizure by low-frequency stimulation in the ventral hippocampus.

    PubMed

    Sun, Hong-Liu; Zhu, Wei; Zhang, Yu-Rong; Pan, Xiao-Hong; Zhang, Jun-Ru; Chen, Xiang-Ming; Liu, Yu-Xia; Li, Shu-Cui; Wang, Qiao-Yun; Deng, Da-Ping

    2017-03-01

    As a promising method for treating intractable epilepsy, the inhibitory effect of low-frequency stimulation (LFS) is well known, although its mechanisms remain unclear. Excessive levels of cerebral glutamate are considered a crucial factor for epilepsy. Therefore, we designed experiments to investigate the crucial parts of the glutamate cycle. We evaluated glutamine synthetase (GS, metabolizes glutamate), glutaminase (synthesizes glutamate), and glutamic acid decarboxylase (GAD, a γ-aminobutyric acid [GABA] synthetase) in different regions of the brain, including the dentate gyrus (DG), CA3, and CA1 subregions of the hippocampus, and the cortex, using western blots, immunohistochemistry, and enzyme activity assays. Additionally, the concentrations of glutamate, GABA, and glutamine (a product of GS) were measured using high-performance liquid chromatography (HPLC) in the same subregions. The results indicated that a transiently promoted glutamate cycle was closely involved in the progression from focal to generalized seizure. Low-frequency stimulation (LFS) delivered to the ventral hippocampus had an antiepileptogenic effect in rats exposed to amygdaloid-kindling stimulation. Simultaneously, LFS could partly reverse the effects of the promoted glutamate cycle, including increased GS function, accelerated glutamate-glutamine cycling, and an unbalanced glutamate/GABA ratio, all of which were induced by amygdaloid kindling in the DG when seizures progressed to stage 4. Moreover, glutamine treatment reversed the antiepileptic effect of LFS with regard to both epileptic severity and susceptibility. Our results suggest that the effects of LFS on the glutamate cycle may contribute to the antiepileptogenic role of LFS in the progression from focal to generalized seizure.

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

    PubMed

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

    2014-04-01

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

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

    PubMed

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

    2011-12-14

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

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

    PubMed Central

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

    2015-01-01

    Peroxisomal proliferator-activated receptor gamma (PPARγ) is a nuclear hormone receptor whose agonist, rosiglitazone has a neuroprotective effect to hippocampal neurons in pilocarpine-induced seizures. Hippocampal slice preparations treated in Mg2+ free medium can induce ictal and interictal-like epileptiform discharges, which is regarded as an in vitro model of N-methyl-D-aspartate (NMDA) receptor-mediated temporal lobe epilepsy (TLE). We applied rosiglitazone in hippocampal slices treated in Mg2+ free medium. The effects of rosiglitazone on hippocampal CA1-Schaffer collateral synaptic transmission were tested. We also examined the neuroprotective effect of rosiglitazone toward NMDA excitotoxicity on cultured hippocampal slices. Application of 10μM rosiglitazone significantly suppressed amplitude and frequency of epileptiform discharges in CA1 neurons. Pretreatment with the PPARγ antagonist GW9662 did not block the effect of rosiglitazone on suppressing discharge frequency, but reverse the effect on suppressing discharge amplitude. Application of rosiglitazone suppressed synaptic transmission in the CA1-Schaffer collateral pathway. By miniature excitatory-potential synaptic current (mEPSC) analysis, rosiglitazone significantly suppressed presynaptic neurotransmitter release. This phenomenon can be reversed by pretreating PPARγ antagonist GW9662. Also, rosiglitazone protected cultured hippocampal slices from NMDA-induced excitotoxicity. The protective effect of 10μM rosiglitazone was partially antagonized by concomitant high dose GW9662 treatment, indicating that this effect is partially mediated by PPARγ receptors. In conclusion, rosiglitazone suppressed NMDA receptor-mediated epileptiform discharges by inhibition of presynaptic neurotransmitter release. Rosiglitazone protected hippocampal slice from NMDA excitotoxicity partially by PPARγ activation. We suggest that rosiglitazone could be a potential agent to treat patients with TLE. PMID:26659605

  10. 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

  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. Lamotrigine Decreased Hippocampal Damage and Improved Vascular Risk Markers in a Rat Model of Pentylenetetrazole Induced Kindling Seizure

    PubMed Central

    Haggag, Basma S; Raafat, Mona H; Abdel Kawy, Hala S

    2014-01-01

    Various antiepileptic drugs (AEDs) especially enzyme-inducing AEDs might be associated with increased vascular risk, through impairment of the endogenous antioxidative ability which may trigger oxygen-dependent tissue injury. Lamotrigine (LTG) a non-enzyme-inducing AED has scarce information regarding its effects on oxidative stress. The present study aimed to study the possible modulation of vascular risk factors of epileptogenesis by LTG, in a rat model of kindling seizure induced by pentylenetetrazole (PTZ). Four groups of male Wister rats were used; vehicle control group, PTZ group (alternate day PTZ, 30 mg/kg, i.p), LTG/PTZ group (LTG 20 mg/kg/day p.o and alternate day PTZ) and LTG group. The study period was 5 weeks. Lipoproteins and total homocysteine (tHcy), malondialdehyde (MDA) and reduced glutathione (GSH) were measured. Aortic endothelial function study and histopathological examination of the rats' brains, aortas and coronaries were conducted. Serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C), tHcy, MDA, GSH levels were significantly higher in epileptic rats than normal controls rats. A decrease in HDL-cholesterol with high atherosclerotic index was also demonstrated. The administration of LTG improved the PTZ-kindled seizures. It produced a significant decrease in TC, TG and LDL-cholesterol, MDA, aortic GSH and increase in HDL-cholesterol with no significant effect on serum GSH and tHcy levels. LTG improved endothelium-dependent relaxation, decreased hippocampal neurodegenerative changes and atherosclerotic changes of aortas and coronaries. LTG decreased seizures severity, hippocampal damage and improved vascular risk markers in this rat model of kindling seizures. PMID:24976768

  13. Exogenous antenatal glucocorticoid treatment reduces susceptibility for hippocampal kindled and maximal electroconvulsive seizures in infant rats.

    PubMed

    Young, Nicole A; Teskey, G Campbell; Henry, Luke C; Edwards, Heather E

    2006-04-01

    Dexamethasone (DEX) and betamethasone (BETA) are synthetic glucocorticoids used clinically to reduce morbidity and mortality in infants at risk of premature birth. While their main role is to facilitate lung development, their effect on the developing nervous system and seizure susceptibility is unclear. The present study tested the hypothesis that antenatal DEX or BETA treatment would alter seizure thresholds and spread of epileptiform activity in the brains of infant offspring. Pregnant dams received once daily injections with DEX, BETA, or vehicle on gestation days 15 to 18. Physical appearance, litter size, and weight of the pups were assessed postnatally. Seizure thresholds were determined on postnatal day 14 using electroconvulsive shock delivered through ear clips (i.e., generalized seizure) or kindling stimulation of the left hippocampus through indwelling electrodes (i.e., partial seizure). The rate of acquisition of kindled seizures was determined on postnatal days 14 and 15. Pups from dams treated with DEX and BETA were growth restricted. Antenatal BETA treatment increased seizure threshold for both models. Antenatal DEX treatment increased kindling threshold, but not electroconvulsive shock threshold. Kindling rate was unaffected by either antenatal treatment. In summary, repeated glucocorticoid treatments had adverse effects on weight, skin and litter size, raised seizure thresholds, and reduced seizure vulnerability. Although these effects are seemingly desirable with respect to seizure susceptibility, they suggest that the functional organization of the nervous system is altered with antenatal synthetic glucocorticoid treatment.

  14. 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

  15. Standing waves as an explanation for generic stationary correlation patterns in noninvasive EEG of focal onset seizures.

    PubMed

    Müller, Markus Franziskus; Rummel, Christian; Goodfellow, Marc; Schindler, Kaspar

    2014-03-01

    Cerebral electrical activity is highly nonstationary because the brain reacts to ever changing external stimuli and continuously monitors internal control circuits. However, a large amount of energy is spent to maintain remarkably stationary activity patterns and functional inter-relations between different brain regions. Here we examine linear EEG correlations in the peri-ictal transition of focal onset seizures, which are typically understood to be manifestations of dramatically changing inter-relations. Contrary to expectations we find stable correlation patterns with a high similarity across different patients and different frequency bands. This skeleton of spatial correlations may be interpreted as a signature of standing waves of electrical brain activity constituting a dynamical ground state. Such a state could promote the formation of spatiotemporal neuronal assemblies and may be important for the integration of information stemming from different local circuits of the functional brain network.

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

    PubMed

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

    2015-04-07

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

  17. Enhanced seizures and hippocampal neurodegeneration following kainic acid-induced seizures in metallothionein-I + II-deficient mice.

    PubMed

    Carrasco, J; Penkowa, M; Hadberg, H; Molinero, A; Hidalgo, J

    2000-07-01

    Metallothioneins (MTs) are major zinc binding proteins in the CNS that could be involved in the control of zinc metabolism as well as in protection against oxidative stress. Mice lacking MT-I and MT-II (MT-I + II deficient) because of targeted gene inactivation were injected with kainic acid (KA), a potent convulsive agent, to examine the neurobiological importance of these MT isoforms. At 35 mg/kg KA, MT-I + II deficient male mice showed a higher number of convulsions and a longer convulsion time than control mice. Three days later, KA-injected mice showed gliosis and neuronal injury in the hippocampus. MT-I + II deficiency decreased both astrogliosis and microgliosis and potentiated neuronal injury and apoptosis as shown by terminal deoxynucleotidyl transferase-mediated in situ end labelling (TUNEL), detection of single stranded DNA (ssDNA) and by increased interleukin-1beta-converting enzyme (ICE) and caspase-3 levels. Histochemically reactive zinc in the hippocampus was increased by KA to a greater extent in MT-I + II-deficient compared with control mice. KA-induced seizures also caused increased oxidative stress, as suggested by the malondialdehyde (MDA) and protein tyrosine nitration (NITT) levels and by the expression of MT-I + II, nuclear factor-kappaB (NF-kappaB), and Cu/Zn-superoxide dismutase (Cu/Zn-SOD). MT-I + II deficiency potentiated the oxidative stress caused by KA. Both KA and MT-I + II deficiency significantly affected the expression of MT-III, granulocyte-macrophage colony stimulating factor (GM-CSF) and its receptor (GM-CSFr). The present results indicate MT-I + II as important for neuron survival during KA-induced seizures, and suggest that both impaired zinc regulation and compromised antioxidant activity contribute to the observed neuropathology of the MT-I + II-deficient mice.

  18. Mice lacking doublecortin and doublecortin-like kinase 2 display altered hippocampal neuronal maturation and spontaneous seizures.

    PubMed

    Kerjan, Géraldine; Koizumi, Hiroyuki; Han, Edward B; Dubé, Celine M; Djakovic, Stevan N; Patrick, Gentry N; Baram, Tallie Z; Heinemann, Stephen F; Gleeson, Joseph G

    2009-04-21

    Mutations in doublecortin (DCX) are associated with intractable epilepsy in humans, due to a severe disorganization of the neocortex and hippocampus known as classical lissencephaly. However, the basis of the epilepsy in lissencephaly remains unclear. To address potential functional redundancy with murin Dcx, we targeted one of the closest homologues, doublecortin-like kinase 2 (Dclk2). Here, we report that Dcx; Dclk2-null mice display frequent spontaneous seizures that originate in the hippocampus, with most animals dying in the first few months of life. Elevated hippocampal expression of c-fos and loss of somatostatin-positive interneurons were identified, both known to correlate with epilepsy. Dcx and Dclk2 are coexpressed in developing hippocampus, and, in their absence, there is dosage-dependent disrupted hippocampal lamination associated with a cell-autonomous simplification of pyramidal dendritic arborizations leading to reduced inhibitory synaptic tone. These data suggest that hippocampal dysmaturation and insufficient receptive field for inhibitory input may underlie the epilepsy in lissencephaly, and suggest potential therapeutic strategies for controlling epilepsy in these patients.

  19. 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

  20. Facilitation of Hippocampal Kindling and Exacerbation of Kindled Seizures by Intra-CA1 Injection of Quinine: A Possible Role of Cx36 Gap Junctions

    PubMed Central

    Etemadi, Fatemeh; Sayyah, Mohammad; Pourbadie, Hamid Gholami; Babapour, Vahab

    2016-01-01

    Background: GABAergic interneurons in the hippocampal CA1 area are mutually communicated by gap junctions (GJs) composed of connexin36 (Cx36). We examined the role of Cx36 in CA1 in manifestation of kindled seizures and hippocampal kindling in rats. Methods: Quinine, as the specific blocker of Cx36, was injected into CA1, and kindled seizures severity was examined 10 min afterward. Moreover, quinine was injected into CA1 once daily, and the rate of CA1 kindling was recorded. Results: Quinine 0.5 and 1 mM caused 2- and 3.5-fold increase in the duration of total seizure behavior and generalized the seizures. Primary and secondary afterdischarges (AD) were also significantly increased. Quinine 0.1 mM augmented the rate of kindling and the growth of secondary AD. Conclusion: Cx36 GJs in CA1 are the main components of hippocampal inhibitory circuit. Any interruption in this path by pathologic or physical damages can trigger hippocampal hyperexcitability and facilitate epileptogenesis. xx PMID:27108691

  1. Excitotoxicity by kainate-induced seizure causes diacylglycerol kinase ζ to shuttle from the nucleus to the cytoplasm in hippocampal neurons.

    PubMed

    Saino-Saito, Sachiko; Hozumi, Yasukazu; Goto, Kaoru

    2011-05-02

    Diacylglycerol kinase (DGK), which consists of several isozymes, plays a pivotal role in lipid second-messenger diacylglycerol metabolism. A nuclear isozyme, DGKζ, which is translocated from the nucleus to the cytoplasm in hippocampal neurons under transient ischemic stress, is implicated in nuclear events of delayed neuronal death. Kainate (KA)-induced seizure is another model used to study excitotoxic stress. Therefore, we examined whether DGKζ is implicated in a different type of degenerative excitotoxicity in hippocampal neurons. We conducted immunohistochemical analysis of rat hippocampi after KA-induced seizures. DGKζ in hippocampal neurons shuttles from the nucleus to the cytoplasm. It never relocates to the nucleus during KA-induced seizures. Marked change in the immunoreactivity is first observed in CA1 pyramidal neurons 2h after injection during stage 3 seizures. Immunoreactivity for DGKι remains unchanged in the cytoplasm. That for NeuN remains mostly unchanged in the nucleus. Results show that nucleocytoplasmic translocation of DGKζ also occurs in a different model of excitotoxicity that results in apoptotic neuronal death. Cytoplasmic translocation of DGKζ might be involved in early events of the apoptotic cell death pathway in hippocampal neurons under stressed conditions.

  2. Seizure Onset Zone Localization from Ictal High-Density EEG in Refractory Focal Epilepsy.

    PubMed

    Staljanssens, Willeke; Strobbe, Gregor; Holen, Roel Van; Birot, Gwénaël; Gschwind, Markus; Seeck, Margitta; Vandenberghe, Stefaan; Vulliémoz, Serge; van Mierlo, Pieter

    2017-03-01

    Epilepsy surgery is the most efficient treatment option for patients with refractory epilepsy. Before surgery, it is of utmost importance to accurately delineate the seizure onset zone (SOZ). Non-invasive EEG is the most used neuroimaging technique to diagnose epilepsy, but it is hard to localize the SOZ from EEG due to its low spatial resolution and because epilepsy is a network disease, with several brain regions becoming active during a seizure. In this work, we propose and validate an approach based on EEG source imaging (ESI) combined with functional connectivity analysis to overcome these problems. We considered both simulations and real data of patients. Ictal epochs of 204-channel EEG and subsets down to 32 channels were analyzed. ESI was done using realistic head models and LORETA was used as inverse technique. The connectivity pattern between the reconstructed sources was calculated, and the source with the highest number of outgoing connections was selected as SOZ. We compared this algorithm with a more straightforward approach, i.e. selecting the source with the highest power after ESI as the SOZ. We found that functional connectivity analysis estimated the SOZ consistently closer to the simulated EZ/RZ than localization based on maximal power. Performance, however, decreased when 128 electrodes or less were used, especially in the realistic data. The results show the added value of functional connectivity analysis for SOZ localization, when the EEG is obtained with a high-density setup. Next to this, the method can potentially be used as objective tool in clinical settings.

  3. Nimodipine prevents early loss of hippocampal CA1 parvalbumin immunoreactivity after focal cerebral ischemia in the rat.

    PubMed

    Benyó, Z; De Jong, G I; Luiten, P G

    1995-01-01

    The effect of focal cerebral ischemia induced by middle cerebral artery occlusion on hippocampal interneurons containing the calcium-binding protein parvalbumin (PV) was studied in rats. Four hours after the onset of ischemia, a reduced number of PV-immunoreactive (-ir) neurons was observed in the lateral part of the CA1 region, while PV-ir was not altered in the CA2 and CA3 areas. Pretreatment with the L-type Ca2+ channel blocker nimodipine prevented the ischemia-induced loss of PV-ir in the CA1, suggesting a role for L-type voltage sensitive calcium channels in the mechanism of early neuronal alterations in the hippocampus CA1 region after focal cerebral ischemia.

  4. Cytochrome c oxidase deficit is associated with the seizure onset zone in young patients with focal cortical dysplasia Type II.

    PubMed

    Miles, Lili; Greiner, Hansel M; Mangano, Francesco T; Horn, Paul S; Leach, James L; Miles, Michael V

    2015-10-01

    It has been postulated that mitochondrial dysfunction may be an important factor in epileptogenesis of intractable epilepsy. The current study tests the hypothesis that mitochondrial Complex IV (CIV) or cytochrome c oxidase dysfunction is associated with the seizure onset zone (SOZ) in patients with focal cortical dysplasia (FCD). Subjects were selected based on: age <19y; epilepsy surgery between May, 2010 and October, 2011; pathological diagnosis of isolated focal cortical dysplasia Type I (FCDI) or Type II (FCDII); and sufficient residual cortical tissue to conduct analysis of electron transport chain complex (ETC) activity in SOZ and adjacent cortical regions. In this retrospective study, patients were identified who had sufficient unfixed, frozen brain tissue for biochemical analysis in tissue homogenates. Specimens were subtyped using ILAE classification for FCD, and excluded if diagnosed with FCD Type III or dual pathology. Analysis of ETC activity in resected tissues was conducted independently and without knowledge of the identity, diagnosis, or clinical status of individual subjects. Seventeen patients met the inclusion criteria, including 6 FCDI and 11 FCDII. Comparison of adjacent cortical resections showed decreased CIV activity in the SOZ of the FCDII group (P = 0.003), but no significant CIV difference in adjacent tissues of the FCDI group. Because of the importance of CIV as the terminal and rate-limiting complex in the mitochondrial electron transport chain, these authors conclude that 1) a deficit of CIV is associated with the SOZ of patients with FCDII; 2) CIV deficiency may contribute to the spectrum of FCD neuropathology; and 3) further investigation of CIV in FCD may lead to the discovery of new targets for neuroprotective therapies for patients with intractable epilepsy.

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

    PubMed Central

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

    2016-01-01

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

  6. 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

  7. 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.

  8. 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

  9. 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.

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

    PubMed Central

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

    2015-01-01

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

  11. Low doses of ethanol markedly potentiate the anti-seizure effect of diazepam in a mouse model of difficult-to-treat focal seizures.

    PubMed

    Klein, Sabine; Bankstahl, Marion; Gramer, Martina; Hausknecht, Maria; Löscher, Wolfgang

    2014-12-01

    Ethanol is commonly used as a solvent in injectable formulations of poorly water-soluble drugs. The concentrations of ethanol in such formulations are generally considered reasonably safe. It is long known that ethanol can potentiate central effects of sedatives and tranquillizers, particularly the benzodiazepines, most likely as a result of a synergistic interaction at the GABAA receptor. However, whether this occurs at the low systemic doses of ethanol resulting from its use as solvent in parenteral formulations of benzodiazepines is not known. In the present study we evaluated whether a commercial ethanol-containing aqueous solution of diazepam exerts more potent anti-seizure effects than an aqueous solution of diazepam hydrochloride or an aqueous emulsion of this drug in the intrahippocampal kainate model of temporal lobe epilepsy in mice. Spontaneous epileptic seizures in this model are known to be resistant to major antiepileptic drugs. Administration of the ethanol-containing formulation of diazepam caused an almost complete suppression of seizures. This was not seen when the same dose (5 mg/kg) of diazepam was administered as aqueous solution or emulsion, although all three diazepam formulations resulted in similar drug and metabolite concentrations in plasma. Our data demonstrate that ethanol-containing solutions of diazepam are superior to block difficult-to-treat seizures to other formulations of diazepam. To our knowledge, this has not been demonstrated before and, if this finding can be translated to humans, may have important consequences for emergency treatment of acute seizures, series of seizures, and initial treatment of status epilepticus in patients.

  12. 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…

  13. 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.

  14. The effects of group III mGluR ligands on pentylenetetrazol-induced kindling of seizures and hippocampal amino acids concentration.

    PubMed

    Maciejak, Piotr; Szyndler, Janusz; Turzyńska, Danuta; Sobolewska, Alicja; Taracha, Ewa; Skórzewska, Anna; Lehner, Małgorzata; Bidziński, Andrzej; Hamed, Adam; Wisłowska-Stanek, Aleksandra; Płaźnik, Adam

    2009-07-28

    Considering the contribution of hippocampal formation and glutamate-mediated signalling to epileptogenesis, we investigated the effects of group III metabotropic glutamate receptor (mGluR)-selective ligands on the kindling of seizures. We also examined the concentration of the amino acid glutamate, GABA, alanine and taurine in the hippocampus of rats using a microdialysis technique. Pentylenetetrazol (PTZ), a non-competitive antagonist of the GABA(A) receptor, was administered intraperitoneally at 35 mg/kg body weight to induce seizures. It was determined that the kindling of PTZ-induced seizures could be attenuated by post intracerebroventricular administration of 100 nmol of the group III mGluR antagonist CPPG [(RS)-a-cyclopropyl-4-phosphonophenylglycine]. There were significant differences in tested parameters during the final stages of the kindling procedure. The group III mGluR agonist L-AP4 [L-(+)-2-amino-4-phosphonobutyric acid at 100 nmol, i.c.v.] did not significantly affect the kindling of seizures in comparison to control rats, although there was acceleration of the process as compared to CPPG treated animals. We demonstrated that the baseline concentrations of glutamate, GABA, alanine, taurine, and the glutamine/GABA ratio were elevated in the hippocampus of fully kindled rats. Intracerebroventricular administration of a single dose of CPPG increased the concentrations of glutamate in the hippocampus of control, non-kindled rats. Intracerebroventricular administration of L-AP4 did not affect the hippocampal amino acid concentration in either animal group. Overall, these data suggest that there is a shift in the balance between neurotransmitters towards increased production of excitatory amino acids, and this may be mediated by group III mGluRs during seizure kindling.

  15. Genetic fate mapping of type-1 stem cell-dependent increase in newborn hippocampal neurons after electroconvulsive seizures.

    PubMed

    Weber, Tillmann; Baier, Vera; Lentz, Katharina; Herrmann, Elke; Krumm, Bertram; Sartorius, Alexander; Kronenberg, Golo; Bartsch, Dusan

    2013-12-01

    Electroconvulsive therapy (ECT) is a uniquely effective treatment for major depressive disorder. An increase in hippocampal neurogenesis is implicated in the recovery from depression. We used an inducible genetic mouse model in which only GFAP-expressing stem-like cells (type-1 cells) and their progeny are selectively labeled with the reporter protein β-galactosidase to track the process of neurogenesis in the dentate gyrus over 3 months following electroconvulsive seizures (ECS), the mouse equivalent of ECT. All ECS protocols tested induced a transient increase in type-1 cell divisions. While this led to an expansion of the type-1 cell pool after high-frequency ECS sessions for 5 consecutive days (5-ECS), asymmetric divisions drove neurogenesis by giving rise to Doublecortin (DCX)-expressing neuroblasts that matured into NeuN+ neurons. Significantly, the increase in newly generated DCX+ and NeuN+ cells after 5-ECS could be traced back to proliferating type-1 cells. Low-frequency continuation ECS (c-ECS) consisting of five single ECS sessions administered every 2 weeks resulted in a similar increase in newborn neurons as the high-frequency 5-ECS protocol. Moreover, the combination of 5-ECS and c-ECS led to a further significant increase in newborn neurons, suggesting a cellular mechanism responsible for the propitious effects of high-frequency ECT followed by continuation ECT in severely depressed patients. The ability of high- and low-frequency ECS to induce normally quiescent type-1 cells to proliferate and generate new neurons sets it apart from other antidepressant treatments and may underlie the superior clinical efficacy of ECT.

  16. Bromocriptine reduces lipid peroxidation and enhances spatial learning and hippocampal neuron survival in a rodent model of focal brain trauma.

    PubMed

    Kline, Anthony E; Massucci, Jaime L; Ma, Xiecheng; Zafonte, Ross D; Dixon, C Edward

    2004-12-01

    Oxidative stress is a significant contributor to the secondary sequelae of traumatic brain injury (TBI), and may mediate subsequent neurobehavioral deficits and histopathology. The present study examined the neuroprotective effects of bromocriptine (BRO), a dopamine D2 receptor agonist with significant antioxidant properties, on cognition, histopathology, and lipid peroxidation in a rodent model of focal brain trauma. BRO (5 mg/kg) or a comparable volume of vehicle (VEH) was administered intraperitoneally 15 min prior to cortical impact or sham injury. In experiment 1, spatial learning was assessed in an established water maze task on post-surgery days 14-18, followed by quantification of hippocampal cell survival and cortical lesion volume at 4 weeks. In experiment 2, rats were sacrificed 1 hr post-surgery, and malondialdehyde (MDA), the end product of lipid peroxidation, was measured in the frontal cortex, striatum, and substantia nigra using a thiobarbituric acid reactive substances assay. The TBI+BRO group was significantly more adept at locating a hidden platform in the water maze compared to the TBI+VEH group and also exhibited a greater percentage of surviving CA3 hippocampal neurons. TBI increased MDA in all examined regions of the VEH-treated, but not BRO-treated group versus SHAMs. MDA was significantly decreased in both the striatum (4.22 +/- 0.52 versus 5.60 +/- 0.44 nmol per mg/tissue +/- SEM) and substantia nigra (4.18 +/- 0.35 versus 7.76 +/- 2.05) of the TBI+BRO versus TBI+VEH groups, respectively, while only a trend toward decreased MDA was observed in the frontal cortex (5.44 +/- 0.44 versus 6.96 +/- 0.77). These findings suggest that TBI-induced oxidative stress is attenuated by acute BRO treatment, which may, in part, explain the benefit in cognitive and histological outcome.

  17. 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.

  18. Progressive Seizure Aggravation in the Repeated 6-Hz Corneal Stimulation Model Is Accompanied by Marked Increase in Hippocampal p-ERK1/2 Immunoreactivity in Neurons

    PubMed Central

    Giordano, Carmela; Costa, Anna M.; Lucchi, Chiara; Leo, Giuseppina; Brunel, Luc; Fehrentz, Jean-Alain; Martinez, Jean; Torsello, Antonio; Biagini, Giuseppe

    2016-01-01

    the third session. The vast majority of p-ERK1/2 immunopositive cells were co-labeled with FosB/ΔFosB antibodies, suggesting the existence of a relationship between the investigated markers in a subpopulation of neurons activated by seizures. These findings suggest that p-ERK1/2 are useful markers to define the aggravation of seizures and the response to anticonvulsant treatments. In particular, p-ERK1/2 expression clearly identified the involvement of hippocampal regions during seizure aggravation in the 6-Hz model. PMID:28018175

  19. 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

  20. Dreaming of seizures.

    PubMed

    Vercueil, Laurent

    2005-08-01

    Could some dreams and temporal lobe seizures share an intrinsic neuronal network? At the interplay of emotion, memory, dream, and temporal lobe seizure, we report on a patient with a left dysplastic amygdala and temporal lobe epilepsy who presented with a typical seizure while dreaming. Neuronal networks subserving affective states are suggested to be involved in emotional dream, memory recall, and amygdalo-hippocampal seizures.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2014-03-01

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

  4. The long-term effects of neonatal morphine administration on the pentylenetetrazol seizure model in rats: the role of hippocampal cholinergic receptors in adulthood.

    PubMed

    Saboory, Ehsan; Gholami, Morteza; Zare, Samad; Roshan-Milani, Shiva

    2014-04-01

    Early life exposure to opiates may affect neuropathological conditions, such as epilepsy, during adulthood. We investigated whether neonatal morphine exposure affects pentylenetetrazol (PTZ)-induced seizures in adulthood. Male rats were subcutaneously injected with morphine or saline on postnatal days 8-14. During adulthood, each rat was assigned to 1 of the following 10 sub-groups: saline, nicotine (0.1, 0.5, or 1 μg), atropine (0.25 or 1 μg), oxotremorine M (0.1 or 1 μg), or mecamylamine (2 or 8 μg). An intrahippocampal infusion of the indicated compound was administered 30 min before seizure induction (80 mg/kg PTZ). Compared with the saline/oxotremorine (1 μg), saline/saline, and morphine/saline groups, the morphine/oxotremorine (1 μg) group showed a significantly increased latency to the first epileptic behavior. The duration of tonic-clonic seizures was significantly lower in the morphine/oxotremorine (1 μg) group compared to the saline/saline and morphine/saline groups. The severity of seizure was significantly decreased in the morphine/atropine (1 μg) group than in the saline/atropine (1 μg). Seizure severity was also decreased in the morphine/mecamylamine (2 μg) group than in the saline/mecamylamine (2 μg) group. Latency for death was significantly lower in the morphine/mecamylamine (2 μg) group compared with the saline/mecamylamine (2 μg) group. Mortality rates in the morphine/atropine (1 μg) and morphine/mecamylamine (2 μg) groups were significantly lower than those in the saline/atropine (1 μg) and saline/mecamylamine (2 μg) groups, respectively. Chronic neonatal morphine administration attenuated PTZ-induced seizures, reduced the mortality rate, and decreased the impact of the hippocampal cholinergic system on seizures and mortality rate in adult rats. Neonatal morphine exposure induces changes to μ-receptors that may lead to activation of GABAergic neurons in the hippocampus. This pathway may explain the anti-convulsant effects of

  5. Alterations of hippocampal GAbaergic system contribute to development of spontaneous recurrent seizures in the rat lithium-pilocarpine model of temporal lobe epilepsy.

    PubMed

    André, V; Marescaux, C; Nehlig, A; Fritschy, J M

    2001-01-01

    Reorganization of excitatory and inhibitory circuits in the hippocampal formation following seizure-induced neuronal loss has been proposed to underlie the development of chronic seizures in temporal lobe epilepsy (TLE). Here, we investigated whether specific morphological alterations of the GABAergic system can be related to the onset of spontaneous recurrent seizures (SRS) in the rat lithium-pilocarpine model of TLE. Immunohistochemical staining for markers of interneurons and their projections, including parvalbumin (PV), calretinin (CR), calbindin (CB), glutamic acid decarboxylase (GAD), and type 1 GABA transporter (GAT1), was performed in brain sections of rats treated with lithium-pilocarpine and sacrificed after 24 h, during the silent phase (6 and 12 days), or after the onset of SRS (10-18 days after treatment). Semiquantitative analysis revealed a selective loss of interneurons in the stratum oriens of CA1, associated with a reduction of GAT1 staining in the stratum radiatum and stratum oriens. In contrast, interneurons in CA3 were largely preserved, although GAT1 staining was also reduced. These changes occurred within 6 days after treatment and were therefore insufficient to cause SRS. In the dentate gyrus, extensive cell loss occurred in the hilus. The pericellular innervation of granule cells by PV-positive axons was markedly reduced, although the loss of PV-interneurons was only partial. Most strikingly, the density of GABAergic axons, positive for both GAD and GAT1, was dramatically increased in the inner molecular layer. This change emerged during the silent period, but was most marked in animals with SRS. Finally, supernumerary CB-positive neurons were detected in the hilus, selectively in rats with SRS. These findings suggest that alterations of GABAergic circuits occur early after lithium-pilocarpine-induced status epilepticus and contribute to epileptogenesis. In particular, the reorganization of GABAergic axons in the dentate gyrus might

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

    PubMed

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

    2015-10-01

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

  7. 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

  8. Voltage-gated Na+ channel II immunoreactivity is selectively up-regulated in hippocampal interneurons of seizure sensitive gerbils.

    PubMed

    Kim, Ji-Eun; Kwak, Sung-Eun; Choi, Hui-Chul; Song, Hong-Ki; Kim, Yeong-In; Jo, Seung-Mook; Kang, Tae-Cheon

    2008-06-27

    In the present study, we investigated the distribution of voltage-gated Na(+) channels (VGSCs) in the normal and epileptic hippocampus of gerbils (a genetic epilepsy model) in order to confirm the relationship between VGSC and seizure activity in these animals. There was no difference of VGSC I immunoreactivity in the hippocampus between seizure-resistant (SR) and seizure sensitive (SS) gerbils. VGSC II immunoreactivity was rarely detected in the perikarya of principal neurons and interneurons in the SR gerbil hippocampus. However, in the SS gerbil hippocampus, VGSC II immunoreactivity was densely observed in the somata of interneurons located in the stratum radiatum and stratum lacunosum-moleculare. Double immunofluorescent study showed immunoreactivity for calretinin (approximately 80% in VGSC II-positive neurons) or calbindin D-28k (approximately 20% in VGSC II-positive neurons) in VGSC II-immunoreactive neurons. VGSC II-immunoreactive neurons did not show parvalbumin immunoreactivity. These findings suggest that seizure activity in SS gerbils may be related to the selective hyperactivation of interneurons in stratum lacunosum-moleculare via the up-regulation of VGSC II expression, which leads to the disinhibition of CA1 pyramidal cells.

  9. Application of correlation dimension and pointwise dimension for non-linear topographical analysis of focal onset seizures.

    PubMed

    Feucht, M; Möller, U; Witte, H; Benninger, F; Asenbaum, S; Prayer, D; Friedrich, M H

    1999-03-01

    For many patients who are candidates for epilepsy surgery, non-invasive evaluation fails to provide sufficient information to permit surgical treatment. Since there are also definite risks and considerable costs associated with invasive procedures, new (non-invasive) techniques are required. This study provides empirical evidence that a non-linear approach applied to ictal surface electroencephalograms (EEGs) can help to delineate the area of seizure onset and may prove useful in complementing visual analysis of the EEG. Multichannel EEGs, recorded from eight patients with different drug-resistant localisation-related epilepsies, were analysed using the concept of correlation dimension and two extensions based on the pointwise dimension. The latter also provided results in cases where assessment of the correlation dimension was not feasible. Comparative values between 2 and 6 were accepted as the result of the algorithms, mostly 3-4 for the EEG channels strongly reflecting epileptic activity, and 4-6 for the other signals. The proportion of accepted pointwise values was usually 200-800% for strong epileptic EEG activity compared to the other data. The approach permitted the characterisation of the scalp area reflecting epileptic activity. The results obtained were in perfect concordance with those obtained during pre-surgical work-up and confirmed by the post-operative outcome.

  10. 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.

  11. 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

  12. 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.

  13. Increase in α-tubulin modifications in the neuronal processes of hippocampal neurons in both kainic acid-induced epileptic seizure and Alzheimer’s disease

    PubMed Central

    Vu, Hang Thi; Akatsu, Hiroyasu; Hashizume, Yoshio; Setou, Mitsutoshi; Ikegami, Koji

    2017-01-01

    Neurodegeneration includes acute changes and slow-developing alterations, both of which partly involve common cellular machinery. During neurodegeneration, neuronal processes are impaired along with dysregulated post-translational modifications (PTMs) of cytoskeletal proteins. In neuronal processes, tubulin undergoes unique PTMs including a branched form of modification called glutamylation and loss of the C-terminal tyrosine residue and the penultimate glutamic acid residue forming Δ2-tubulin. Here, we investigated the state of two PTMs, glutamylation and Δ2 form, in both acute and slow-developing neurodegenerations, using a newly generated monoclonal antibody, DTE41, which had 2-fold higher affinity to glutamylated Δ2-tubulin, than to unmodified Δ2-tubulin. DTE41 recognised glutamylated Δ2-tubulin preferentially in immunostaining than in enzyme-linked immunosorbent assay and immunoblotting. In normal mouse brain, DTE41 stained molecular layer of the cerebellum as well as synapse-rich regions in pyramidal neurons of the cerebral cortex. In kainic acid-induced epileptic seizure, DTE41-labelled signals were increased in the hippocampal CA3 region, especially in the stratum lucidum. In the hippocampi of post-mortem patients with Alzheimer’s disease, intensities of DTE41 staining were increased in mossy fibres in the CA3 region as well as in apical dendrites of the pyramidal neurons. Our findings indicate that glutamylation on Δ2-tubulin is increased in both acute and slow-developing neurodegeneration. PMID:28067280

  14. Lipoic acid inhibits caspase-dependent and -independent cell death pathways and is neuroprotective against hippocampal damage after pilocarpine-induced seizures.

    PubMed

    dos Santos, Pauline Sousa; Feitosa, Chistiane Mendes; Saldanha, Gláucio Barros; Tomé, Adriana da Rocha; Feng, Dejiang; de Freitas, Rivelilson Mendes

    2011-01-01

    Alpha-lipoic acid has some neuroprotective properties, but this action has not been investigated in models of epilepsy. The aim of the present study was to investigate the protective efficacy of α-lipoic acid (lipoic acid) against pilocarpine-induced cell death through the caspase-dependent or -independent mitochondrial apoptotic pathways. Wistar rats were injected intraperitoneally with 0.9% saline (control group), pilocarpine (400 mg/kg, pilocarpine group) alone, or α-lipoic acid (20 mg/kg) in association with pilocarpine (400 mg/kg) 30 min before administration of α-lipoic acid. After the treatments all groups were observed for 24 h. Cell death was reduced in lipoic acid-treated rats. Cytosolic translocation of cytochrome c and subsequent activation of caspase-3 were reduced by lipoic acid treatment. AIF nuclear translocation and subsequent large-scale DNA fragmentation were also decreased in lipoic acid-treated rats. Our study suggests that lipoic acid inhibits both caspase-dependent and -independent apoptotic pathways and may be neuroprotective against hippocampal damage during pilocarpine-induced seizures.

  15. Bumetanide reduce the seizure susceptibility induced by pentylenetetrazol via inhibition of aberrant hippocampal neurogenesis in neonatal rats after hypoxia-ischemia.

    PubMed

    Hu, Jiang-Jian; Yang, Xing-Liang; Luo, Wen-Di; Han, Song; Yin, Jun; Liu, Wan-Hong; He, Xiao-Hua; Peng, Bi-Wen

    2017-02-02

    Hypoxia-ischemia brain damage (HIBD) is one of prevalent causes of neonatal mortality and morbidity. Our data demonstrated that hypoxia-ischemia (HI) induced Na(+)-K(+)-Cl(-)-co-transporter 1 (NKCC1) increasing in hippocampus. Previous studies demonstrated that NKCC1 regulates various stages of neurogenesis. In this study, we studied the role of increased NKCC1 in regulating of HI-induced neurogenesis. HIBD model was established in 7days old Sprague-Dawley rat pup, and the expression of NKCC1 was detected by western blot and qPCR. Brain electrical activity in freely rats was monitored by electroencephalography (EEG) recordings. HI-induced neurogenesis was detected by immunofluorescence staining. Neurobehavioral test was to investigate the neuro-protective role of bumetanide, an inhibitor of NKCC1, on neonatal rats after HI. The results showed that bumetanide treatment significantly reduced brain electrical activity and the seizure stage of epilepsy induced by pentylenetetrazol (PTZ) in vivo after HI. In addition, bumetanide restored aberrant hippocampal neurogenesis and associated cognitive function. Our data demonstrated that bumetanide reduces the susceptibility of epilepsy induced by PTZ in rats suffering from HI injury during neonatal period via restoring the ectopic newborn neurons in dentate gyrus (DG) and cognitive function.

  16. Transition to seizure: ictal discharge is preceded by exhausted presynaptic GABA release in the hippocampal CA3 region.

    PubMed

    Zhang, Zhang J; Koifman, Julius; Shin, Damian S; Ye, Hui; Florez, Carlos M; Zhang, Liang; Valiante, Taufik A; Carlen, Peter L

    2012-02-15

    How the brain transitions into a seizure is poorly understood. Recurrent seizure-like events (SLEs) in low-Mg2+/ high-K+ perfusate were measured in the CA3 region of the intact mouse hippocampus. The SLE was divided into a "preictal phase," which abruptly turns into a higher frequency "ictal" phase. Blockade of GABA(A) receptors shortened the preictal phase, abolished interictal bursts, and attenuated the slow preictal depolarization, with no effect on the ictal duration, whereas SLEs were blocked by glutamate receptor blockade. In CA3 pyramidal cells and stratum oriens non-fast-spiking and fast-spiking interneurons, recurrent GABAergic IPSCs predominated interictally and during the early preictal phase, synchronous with extracellularly measured recurrent field potentials (FPs). These IPSCs then decreased to zero or reversed polarity by the onset of the higher-frequency ictus. However, postsynaptic muscimol-evoked GABA(A) responses remained intact. Simultaneously, EPSCs synchronous with the FPs markedly increased to a maximum at the ictal onset. The reversal potential of the compound postsynaptic currents (combined simultaneous EPSCs and IPSCs) became markedly depolarized during the preictal phase, whereas the muscimol-evoked GABA(A) reversal potential remained unchanged. During the late preictal phase, interneuronal excitability was high, but IPSCs, evoked by local stimulation, or osmotically by hypertonic sucrose application, were diminished, disappearing at the ictal onset. We conclude that the interictal and early preictal states are dominated by GABAergic activity, with the onset of the ictus heralded by exhaustion of presynaptic release of GABA, and unopposed increased glutamatergic responses.

  17. [Gelastic seizures: etiology, semiology, therapeutic perspectives].

    PubMed

    Usacheva, E L; Mukhin, K Iu; Prityko, A G; Aĭvazian, S O; Kharlamov, L A; Shorina, M Iu

    2003-01-01

    Gelastic seizures (laughing seizures) are a rare type of epileptic seizure in which laugh in a main and dominating manifestation of the seizure. As a rule, the seizures are caused by organic cerebral pathology and are often reported as a specific epilepsy marker related to hypothalamic hamartoma. The interictal EEG frequently shows a focal activity. Based on examination of 2 patients with gelastic seizures and hypothalamic hamartoma, clinical features, EEG characteristics and therapeutic perspectives for the disorder are discussed.

  18. Ketone ester supplementation attenuates seizure activity, and improves behavior and hippocampal synaptic plasticity in an Angelman syndrome mouse model.

    PubMed

    Ciarlone, Stephanie L; Grieco, Joseph C; D'Agostino, Dominic P; Weeber, Edwin J

    2016-12-01

    Angelman syndrome (AS) is a rare genetic and neurological disorder presenting with seizures, developmental delay, ataxia, and lack of speech. Previous studies have indicated that oxidative stress-dependent metabolic dysfunction may underlie the phenotypic deficits reported in the AS mouse model. While the ketogenic diet (KD) has been used to protect against oxidative stress and has successfully treated refractory epilepsy in AS case studies, issues arise due to its strict adherence requirements, in addition to selective eating habits and weight issues reported in patients with AS. We hypothesized that ketone ester supplementation would mimic the KD as an anticonvulsant and improve the behavioral and synaptic plasticity deficits in vivo. AS mice were supplemented R,S-1,3-butanediol acetoacetate diester (KE) ad libitum for eight weeks. KE administration improved motor coordination, learning and memory, and synaptic plasticity in AS mice. The KE was also anticonvulsant and altered brain amino acid metabolism in AS treated animals. Our findings suggest that KE supplementation produces sustained ketosis and ameliorates many phenotypes in the AS mouse model, and should be investigated further for future clinical use.

  19. Water maze experience and prenatal choline supplementation differentially promote long-term hippocampal recovery from seizures in adulthood.

    PubMed

    Wong-Goodrich, Sarah J E; Glenn, Melissa J; Mellott, Tiffany J; Liu, Yi B; Blusztajn, Jan K; Williams, Christina L

    2011-06-01

    Status epilepticus (SE) in adulthood dramatically alters the hippocampus and produces spatial learning and memory deficits. Some factors, like environmental enrichment and exercise, may promote functional recovery from SE. Prenatal choline supplementation (SUP) also protects against spatial memory deficits observed shortly after SE in adulthood, and we have previously reported that SUP attenuates the neuropathological response to SE in the adult hippocampus just 16 days after SE. It is unknown whether SUP can ameliorate longer-term cognitive and neuropathological consequences of SE, whether repeatedly engaging the injured hippocampus in a cognitive task might facilitate recovery from SE, and whether our prophylactic prenatal dietary treatment would enable the injured hippocampus to more effectively benefit from cognitive rehabilitation. To address these issues, adult offspring from rat dams that received either a control (CON) or SUP diet on embryonic days 12-17 first received training on a place learning water maze task (WM) and were then administered saline or kainic acid (KA) to induce SE. Rats then either remained in their home cage, or received three additional WM sessions at 3, 6.5, and 10 weeks after SE to test spatial learning and memory retention. Eleven weeks after SE, the brains were analyzed for several hippocampal markers known to be altered by SE. SUP attenuated SE-induced spatial learning deficits and completely rescued spatial memory retention by 10 weeks post-SE. Repeated WM experience prevented SE-induced declines in glutamic acid decarboxylase (GAD) and dentate gyrus neurogenesis, and attenuated increased glial fibrilary acidic protein (GFAP) levels. Remarkably, SUP alone was similarly protective to an even greater extent, and SUP rats that were water maze trained after SE showed reduced hilar migration of newborn neurons. These findings suggest that prophylactic SUP is protective against the long-term cognitive and neuropathological effects of

  20. Enhanced Burst-Suppression and Disruption of Local Field Potential Synchrony in a Mouse Model of Focal Cortical Dysplasia Exhibiting Spike-Wave Seizures

    PubMed Central

    Williams, Anthony J.; Zhou, Chen; Sun, Qian-Quan

    2016-01-01

    Focal cortical dysplasias (FCDs) are a common cause of brain seizures and are often associated with intractable epilepsy. Here we evaluated aberrant brain neurophysiology in an in vivo mouse model of FCD induced by neonatal freeze lesions (FLs) to the right cortical hemisphere (near S1). Linear multi-electrode arrays were used to record extracellular potentials from cortical and subcortical brain regions near the FL in anesthetized mice (5–13 months old) followed by 24 h cortical electroencephalogram (EEG) recordings. Results indicated that FL animals exhibit a high prevalence of spontaneous spike-wave discharges (SWDs), predominately during sleep (EEG), and an increase in the incidence of hyper-excitable burst/suppression activity under general anesthesia (extracellular recordings, 0.5%–3.0% isoflurane). Brief periods of burst activity in the local field potential (LFP) typically presented as an arrhythmic pattern of increased theta-alpha spectral peaks (4–12 Hz) on a background of low-amplitude delta activity (1–4 Hz), were associated with an increase in spontaneous spiking of cortical neurons, and were highly synchronized in control animals across recording sites in both cortical and subcortical layers (average cross-correlation values ranging from +0.73 to +1.0) with minimal phase shift between electrodes. However, in FL animals, cortical vs. subcortical burst activity was strongly out of phase with significantly lower cross-correlation values compared to controls (average values of −0.1 to +0.5, P < 0.05 between groups). In particular, a marked reduction in the level of synchronous burst activity was observed, the closer the recording electrodes were to the malformation (Pearson’s Correlation = 0.525, P < 0.05). In a subset of FL animals (3/9), burst activity also included a spike or spike-wave pattern similar to the SWDs observed in unanesthetized animals. In summary, neonatal FLs increased the hyperexcitable pattern of burst activity induced by

  1. Seizure-Induced Axonal Sprouting: Assessing Connections Between Injury, Local Circuits, and Epileptogenesis

    PubMed Central

    Sutula, Thomas

    2002-01-01

    Neurons and neural circuits undergo extensive structural and functional remodeling in response to seizures. Sprouting of axons in the mossy fiber pathway of the hippocampus is a prominent example of a seizure-induced structural alteration which has received particular attention because it is easily detected, is induced by intense or repeated brief seizures in focal chronic models of epilepsy, and is also observed in the human epileptic hippocampus. During the last decade the association of mossy fiber sprouting with seizures and epilepsy has been firmly established. Many anatomical features of mossy fiber sprouting have been described in considerable detail, and there is evidence that sprouting occurs in a variety of other pathways in association with seizures and injury. There is uncertainty, however, about how or when mossy fiber sprouting may contribute to hippocampal dysfunction and generation of seizures. Study of mossy fiber sprouting has provided a strong theoretical and conceptual framework for efforts to understand how seizures and injury may contribute to epileptogenesis and its consequences. It is likely that investigation of mossy fiber sprouting will continure to offer significant opportunities for insights into seizure-induced plasticity of neural circuits at molecular, cellular, and systems levels. PMID:15309153

  2. 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. ...

  3. 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.

  4. 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].

  5. Classification of seizures and epilepsy.

    PubMed

    Riviello, James J

    2003-07-01

    The management of seizures and epilepsy begins with forming a differential diagnosis, making the diagnosis, and then classifying seizure type and epileptic syndrome. Classification guides treatment, including ancillary testing, management, prognosis, and if needed, selection of the appropriate antiepileptic drug (AED). Many AEDs are available, and certain seizure types or epilepsy syndromes respond to specific AEDs. The identification of the genetics, molecular basis, and pathophysiologic mechanisms of epilepsy has resulted from classification of specific epileptic syndromes. The classification system used by the International League Against Epilepsy is periodically revised. The proposed revision changes the classification emphasis from the anatomic origin of seizures (focal vs generalized) to seizure semiology (ie, the signs or clinical manifestations). Modified systems have been developed for specific circumstances (eg, neonatal seizures, infantile seizures, status epilepticus, and epilepsy surgery). This article reviews seizure and epilepsy classification, emphasizing new data.

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

    PubMed

    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; Kneen, Rachel

    2013-05-01

    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.

  7. Gelastic seizures: not always hypothalamic hamartoma.

    PubMed

    Cheung, Christina S; Parrent, Andrew G; Burneo, Jorge G

    2007-12-01

    Gelastic seizures are often associated with hypothalamic hamartomas. However, focal cortical dysplasias can also cause "laughing seizures", and such cases can be difficult to localize with EEG. This case report presents a 29-year-old woman who was successfully rendered free of gelastic seizures after resection of a frontal cortical dysplasia, localized through MRI and SPECT imaging.[Published with video sequences].

  8. Progressive neuronal activation accompanies epileptogenesis caused by hippocampal glutamine synthetase inhibition.

    PubMed

    Albright, Benjamin; Dhaher, Roni; Wang, Helen; Harb, Roa; Lee, Tih-Shih W; Zaveri, Hitten; Eid, Tore

    2017-02-01

    Loss of glutamine synthetase (GS) in hippocampal astrocytes has been implicated in the causation of human mesial temporal lobe epilepsy (MTLE). However, the mechanism by which the deficiency in GS leads to epilepsy is incompletely understood. Here we ask how hippocampal GS inhibition affects seizure phenotype and neuronal activation during epilepsy development (epileptogenesis). Epileptogenesis was induced by infusing the irreversible GS blocker methionine sulfoximine (MSO) unilaterally into the hippocampal formation of rats. We then used continuous video-intracranial electroencephalogram (EEG) monitoring and c-Fos immunohistochemistry to determine the type of seizures and spatial distribution of neuronal activation early (1-5days postinfusion) and late (16-43days postinfusion) in epileptogenesis. Early in epileptogenesis, seizures were preferentially mild (stage 1-2), activating neurons in the entorhinal-hippocampal area, the basolateral amygdala, the piriform cortex, the midline thalamus, and the anterior olfactory area. Late in epileptogenesis, the seizures were generally more severe (stages 4-5) with neuronal activation extending to the neocortex, the bed nucleus of the stria terminalis, the mediodorsal thalamu\\s, and the central nucleus of the amygdala. Our findings demonstrate that inhibition of GS focally in the hippocampal formation triggers a process of epileptogenesis characterized by gradual worsening of seizure severity and involvement of progressively larger neuronal populations over a period of several weeks. Knowledge about the underlying mechanism of epileptogenesis is important because such knowledge may result in more specific and efficacious treatments of MTLE by moving away from large and poorly specific surgical resections to highly targeted surgical or pharmacological interventions of the epileptogenic process.

  9. Absence Seizure (Petit Mal Seizure)

    MedlinePlus

    ... Staff Absence seizures involve brief, sudden lapses of consciousness. They're more common in children than adults. ... have seizures, the brain's usual electrical activity is altered. During an absence seizure, these electrical signals repeat ...

  10. Neurocysticercosis and microscopic hippocampal dysplasia in a patient with refractory mesial temporal lobe epilepsy.

    PubMed

    da Silva, Alexandre Valotta; Martins, Heloise Helena; Marques, Carolina Mattos; Yacubian, Elza Marcia Targas; Sakamoto, Américo Ceiki; Carrete, Henrique; da Silva Centeno, Ricardo; Stavale, João Norberto; Cavalheiro, Esper Abrão

    2006-06-01

    Epidemiologic studies suggest that neurocysticercosis (NC) is the main cause of symptomatic epilepsy in developing countries. The association between NC and mesial temporal lobe epilepsy (MTLE) has been reported by several authors. Recent data have shown that the presence of NC does not influence the clinical and pathological profile in MTLE patients and suggest that not all cysticercotic lesions are inevitably epileptogenic. We describe a 50-years-old woman with partial seizures due to NC which evolve to MTLE. The patient was submitted to a corticoamygdalohippocampectomy to treat refractory epilepsy. An immunohistochemical study using neuronal markers was made on hippocampal formation. Besides the typical aspects of Ammon's horn sclerosis (AHS), the microscopic examination demonstrates cellular features of hippocampal malformation including dysmorphic neurons and focal bilamination of granular cell layer. We suggest that, in this case, a developmental disorder lowered the threshold for the NC-induced seizures and contributed to the establishment of refractory epilepsy.

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

    PubMed

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

    2011-08-01

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

  12. Beta/gamma oscillatory activity in the CA3 hippocampal area is depressed by aberrant GABAergic transmission from the dentate gyrus after seizures.

    PubMed

    Treviño, Mario; Vivar, Carmen; Gutiérrez, Rafael

    2007-01-03

    Oscillatory activity in the CA3 region is thought to be involved in the encoding and retrieval of information. These oscillations originate from the recurrent excitation between pyramidal cells that are entrained by the synchronous rhythmic inhibition of local interneurons. We show here that, after seizures, the dentate gyrus (DG) tonically inhibits beta/gamma (20-24 Hz) field oscillations in the CA3 area through GABA-mediated signaling. These oscillations originate in the interneuron network because they are maintained in the presence of ionotropic glutamate receptor antagonists, and they can be blocked by GABA(A) receptor antagonists or by perfusion of a calcium-free extracellular medium. Inhibition of this oscillatory activity requires intact DG-to-CA3 connections, and it is suppressed by the activation of metabotropic glutamate receptors (mGluR). The influence of mGluR activation was reflected in the spontaneous subthreshold membrane oscillations of CA3 interneurons after one seizure but could also be observed in pyramidal cells after several seizures. Coincident stimulation of the DG at and beta/gamma frequencies produced a frequency-dependent excitation of interneurons and the inhibition of pyramidal cells. Indeed, these effects were maximal at the frequency that matched the mGluR-sensitive spontaneous field oscillations, suggesting a resonance phenomenon. Our results shed light on the mechanisms that may underlie the deficits in memory and cognition observed after epileptic seizures.

  13. [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.

  14. Gelastic seizures involving the left parietal lobe.

    PubMed

    Machado, René Andrade; Astencio, Adriana Goicoechea

    2012-01-01

    Gelastic seizures have been described in various epilepsies arising from the temporal or frontal lobes, although the most commonly encountered form is related to the presence of a hypothalamic hamartoma. We describe a patient with gelastic seizures involving the left parietal lobe. Our patient, an 8-year-old girl, underwent interictal video/EEG monitoring and MRI. The seizures consisted of brief staring followed by smiling and laughing. Electroencephalography during the gelastic seizures showed rhythmic spikes and waves in the left parietal lobe. MRI revealed the characteristic features of focal cortical dysplasia. Our findings suggest that the left parietal lobe may actively participate in the particular epileptogenic network generating gelastic seizures.

  15. Mice deficient for the extracellular matrix glycoprotein tenascin-r show physiological and structural hallmarks of increased hippocampal excitability, but no increased susceptibility to seizures in the pilocarpine model of epilepsy.

    PubMed

    Brenneke, F; Bukalo, O; Dityatev, A; Lie, A A

    2004-01-01

    Recognition molecules provide important cues for neuronal survival, axonal fasciculation, axonal pathfinding, synaptogenesis, synaptic plasticity, and regeneration. Our previous studies revealed a link between perisomatic inhibition and the extracellular matrix glycoprotein tenascin-R (TN-R). Therefore, we here studied neuronal excitability and epileptic susceptibility in mice constitutively deficient in TN-R. In vitro analysis of populational spikes in hippocampal slices of TN-R-deficient mice revealed a significant increase in multiple spikes in the CA1 region, as compared with wild-type mice. This difference between genotypes was only partially reduced after blockade of GABA(A) receptors with picrotoxin, indicating a deficit in GABAergic inhibition and an increase in intrinsic excitability of CA1 pyramidal cells in TN-R-deficient mice. Using a battery of immunohistochemical markers and histological stainings, we were able to identify two abnormalities in the hippocampus of TN-R-deficient mice possibly related to increased excitability: the high number of glial fibrillary acidic protein-positive astrocytes and low number of calretinin-positive interneurons in the CA1 and CA3 regions. In order to test whether the revealed abnormalities give rise to increased susceptibility to seizures in TN-R-deficient mice, we used the pilocarpine model of epilepsy. No genotype-specific differences were found with regard to the time-course of pilocarpine-induced and spontaneous seizures, neuronal cell loss, aberrant sprouting and distribution of synaptic and inhibitory interneuron markers. However, pilocarpine-induced astrogliosis and reduction in calretinin-positive interneurons were less pronounced in TN-R mutants, thereby resulting in an occlusion of effects induced by TN-R deficiency and pilocarpine. Thus, TN-R-deficient mutants show several electrophysiological and morphological hallmarks of increased neuronal excitability, which, however, do not give rise to more

  16. Possible involvement of NO/NOS signaling in hippocampal amyloid-beta production induced by transient focal cerebral ischemia in aged rats.

    PubMed

    Li, Song; Wang, Wei; Wang, Che; Tang, Yi-Yuan

    2010-02-12

    In the present study, to define the roles of nitric oxide (NO) signaling in amyloid-beta (A beta) production after transient cerebral ischemia, extracellular levels of NO and A beta were monitored by intracerebral microdialysis in the hippocampus of aged rats exposed to transient middle cerebral artery occlusion and reperfusion (MCAO/R). The results indicated that 1-h MCAO significantly upregulated hippocampal NO and A beta levels. In addition, the NO elevation preceded the A beta changes. The Western blotting suggested that acute hypoperfusion could increase the expression of beta-secretase 1 (BACE1) but not BACE2. The enhanced NO concentration in acute stage of MCAO/R was coincident with increased eNOS expression, while in subacute stage was coincident with increased iNOS and nNOS. Our results also indicated that pretreatment of L-NAME, one non-selective NOS inhibitor could decrease the BACE1 expression, reverse both NO and A beta changes and rescue the delayed neuronal death. These preliminary findings indicated that activation of NOS/NO signaling system could trigger A beta production through BACE1 pathway during acute ischemic episode. The present data may be important in understanding, at least in part, the pathological role of NO/NOS system involved in hippocampal A beta production and neuronal damage induced by transient cerebral ischemia.

  17. Carbon monoxide offers neuroprotection from hippocampal cell damage induced by recurrent febrile seizures through the PERK-activated ER stress pathway.

    PubMed

    Han, Ying; Yi, Wenxia; Qin, Jiong; Zhao, Yang; Zhang, Jing; Chang, Xingzhi

    2015-01-12

    Carbon monoxide (CO) is neuroprotective in various models of brain injury, but the precise mechanisms for this are yet to be established. In the present study, using a rat model of recurrent febrile seizures (FSs), we found an increase in plasma CO, evidence of neuronal damage and apoptosis, an increase in the expression of the endoplasmic reticulum stress (ERS) marker glucose-regulated protein 78 (GRP78) and C/EBP homologous binding protein (CHOP), and an increase in phosphorylated protein kinase RNA-like endoplasmic reticulum kinase (p-PERK)/eukaryotic translation initiation factor 2 alpha (p-eIF2α) in the hippocampus after 10 FSs. Administration of Hemin (a CO donor) in FS rats alleviated the neuronal damage, reduced neuronal apoptosis, upregulated GRP78 expression, decreased CHOP, and increased p-PERK and p-eIF2α expression in the hippocampus, compared to FS control rats. In contrast, treating FS rats with ZnPP-IX (a CO synthase inhibitor) aggravated the neuronal damage, enhanced neuronal apoptosis, downregulated GRP78 expression, increased CHOP, and decreased p-PERK and p-eIF2α expression, compared to FS control rats. These results suggest that endogenous CO limits the neuronal damage induced by recurrent FSs, through the PERK-activated ERS pathway.

  18. A gain-of-function mutation in the sodium channel gene Scn2a results in seizures and behavioral abnormalities.

    PubMed

    Kearney, J A; Plummer, N W; Smith, M R; Kapur, J; Cummins, T R; Waxman, S G; Goldin, A L; Meisler, M H

    2001-01-01

    The GAL879-881QQQ mutation in the cytoplasmic S4-S5 linker of domain 2 of the rat brain IIA sodium channel (Na(v)1.2) results in slowed inactivation and increased persistent current when expressed in Xenopus oocytes. The neuron-specific enolase promoter was used to direct in vivo expression of the mutated channel in transgenic mice. Three transgenic lines exhibited seizures, and line Q54 was characterized in detail. The seizures in these mice began at two months of age and were accompanied by behavioral arrest and stereotyped repetitive behaviors. Continuous electroencephalogram monitoring detected focal seizure activity in the hippocampus, which in some instances generalized to involve the cortex. Hippocampal CA1 neurons isolated from presymptomatic Q54 mice exhibited increased persistent sodium current which may underlie hyperexcitability in the hippocampus. During the progression of the disorder there was extensive cell loss and gliosis within the hippocampus in areas CA1, CA2, CA3 and the hilus. The lifespan of Q54 mice was shortened and only 25% of the mice survived beyond six months of age. Four independent transgenic lines expressing the wild-type sodium channel were examined and did not exhibit any abnormalities. The transgenic Q54 mice provide a genetic model that will be useful for testing the effect of pharmacological intervention on progression of seizures caused by sodium channel dysfunction. The human ortholog, SCN2A, is a candidate gene for seizure disorders mapped to chromosome 2q22-24.

  19. Febrile seizures

    MedlinePlus

    Seizure - fever induced; Febrile convulsions ... an illness. It may not occur when the fever is highest. A cold or viral illness may ... other than symptoms of the illness causing the fever. Often, the child will not need a full ...

  20. 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).

  1. Do Single Seizures Cause Neuronal Death in the Human Hippocampus?

    PubMed Central

    Rocha, Luisa L; Lopez-Meraz, Maria-Leonor; Niquet, Jerome; Wasterlain, Claude G

    2007-01-01

    The question of whether repeated single seizures cause neuronal death in the adult human brain is of great clinical importance and might have broad therapeutic implications. Reviewed here are recent studies on the effects of repeated single seizures (in the absence of status epilepticus) on hippocampal volume and on neuronal death markers in blood and in surgically ablated hippocampi. PMID:17520081

  2. 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…

  3. Epileptic seizure after treatment with thiocolchicoside

    PubMed Central

    Giavina-Bianchi, Pedro; Giavina-Bianchi, Mara; Tanno, Luciana Kase; Ensina, Luis Felipe Chiaverini; Motta, Antôno Abílio; Kalil, Jorge

    2009-01-01

    Background: Adverse drug reactions are important determinants of inpatient and outpatient morbidity. Thiocolchicoside is a semisynthetic derivate of naturally occurring colchicoside, which is largely used in humans as a centrally acting muscle relaxant. Epileptic seizures after thiocolchicoside intake have been reported in individuals with a history of epilepsy, acute brain injury or possible blood–brain barrier disruption. Case report: We report the case of a 66-year-old male patient presenting a sudden epileptic seizure temporally related to the intake of thiocolchicoside for muscle contracture and pain. The probably causes of the seizures were thiocolchicoside intake and cerebral microhemorrhages attributed to cerebral amyloid angiopathy. Discussion: Drugs only rarely cause focal seizures. Our case indicates that thiocolchicoside can precipitate seizures in predisposed patients, and that its use should be avoided in patients with brain diseases (and therefore lower seizure thresholds) or blood–brain barrier disruption. This information should be provided in the drug package insert. PMID:19707540

  4. 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

  5. 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

    2015-03-26

    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.

  6. Hippocampal Formation Maldevelopment and Sudden Unexpected Death across the Pediatric Age Spectrum.

    PubMed

    Kinney, Hannah C; Poduri, Annapurna H; Cryan, Jane B; Haynes, Robin L; Teot, Lisa; Sleeper, Lynn A; Holm, Ingrid A; Berry, Gerald T; Prabhu, Sanjay P; Warfield, Simon K; Brownstein, Catherine; Abram, Harry S; Kruer, Michael; Kemp, Walter L; Hargitai, Beata; Gastrang, Joanne; Mena, Othon J; Haas, Elisabeth A; Dastjerdi, Roya; Armstrong, Dawna D; Goldstein, Richard D

    2016-10-01

    Sudden infant death syndrome (SIDS) and sudden unexplained death in childhood (SUDC) are defined as sudden death in a child remaining unexplained despite autopsy and death scene investigation. They are distinguished from each other by age criteria, i.e. with SIDS under 1 year and SUDC over 1 year. Our separate studies of SIDS and SUDC provide evidence of shared hippocampal abnormalities, specifically focal dentate bilamination, a lesion classically associated with temporal lobe epilepsy, across the 2 groups. In this study, we characterized the clinicopathologic features in a retrospective case series of 32 children with sudden death and hippocampal formation (HF) maldevelopment. The greatest frequency of deaths was between 3 weeks and 3 years (81%, 26/32). Dentate anomalies were found across the pediatric age spectrum, supporting a common vulnerability that defies the 1-year age cutoff between SIDS and SUDC. Twelve cases (38%) had seizures, including 7 only with febrile seizures. Subicular anomalies were found in cases over 1 year of age and were associated with increased risk of febrile seizures. Sudden death associated with HF maldevelopment reflects a complex interaction of intrinsic and extrinsic factors that lead to death at different pediatric ages, and may be analogous to sudden unexplained death in epilepsy.

  7. Evaluation of first nonfebrile seizures.

    PubMed

    Wilden, Jessica A; Cohen-Gadol, Aaron A

    2012-08-15

    Nonfebrile seizures may indicate underlying disease or epilepsy. The patient history can often distinguish epileptic seizures from nonepileptic disorders by identifying the events directly preceding the convulsion, associated conditions, and details of the seizure, including triggers, length, and type of movements. Laboratory testing, lumbar puncture, and neuroimaging may be indicated depending on the presentation, suspected etiology, and patient's age. Electroencephalography should be performed 24 to 48 hours after a first seizure because of its substantial yield and ability to predict recurrence. Neuroimaging is recommended for adults, infants, and children who have cognitive or motor developmental delay or a focal seizure. Neuroimaging may be scheduled on an outpatient basis for patients with stable vital signs who are awake and have returned to neurologic baseline. Emergent neuroimaging should be performed in patients with persistent decreased mental status or a new focal neurologic abnormality. Although magnetic resonance imaging is generally preferred to head computed tomography because of its greater sensitivity for intracranial pathology, computed tomography should be performed if intracranial bleeding is suspected because of recent head trauma, coagulopathy, or severe headache. Treatment with an antiepileptic drug after a first seizure does not prevent epilepsy in the long term, but it decreases the short-term likelihood of a second seizure. Adults with an unremarkable neurologic examination, no comorbidities, and no known structural brain disease who have returned to neurologic baseline do not need to be started on antiepileptic therapy. Treatment decisions should weigh the benefit of decreased short-term risk of recurrence against the potential adverse effects of antiepileptic drugs.

  8. 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.

  9. 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].

  10. Frontal Lobe Seizures

    MedlinePlus

    Frontal lobe seizures Overview By Mayo Clinic Staff Frontal lobe seizures are a common form of epilepsy, a ... seizures originate in the front of the brain. Frontal lobe seizures may also be caused by abnormal brain ...

  11. 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…

  12. Genetic effects on sleep/wake variation of seizures

    PubMed Central

    Winawer, Melodie R.; Shih, Jerry; Beck, Erin S.; Hunter, Jessica E.; Epstein, Michael P.

    2016-01-01

    Summary Objective There is a complex bidirectional relationship between sleep and epilepsy. Sleep/wake timing of seizures has been investigated for several individual seizure types and syndromes, but few large-scale studies of the timing of seizures exist in people with varied epilepsy types. In addition, the genetic contributions to seizure timing have not been well studied. Methods Sleep/wake timing of seizures was determined for 1,395 subjects in 546 families enrolled in the Epilepsy Phenome/Genome Project (EPGP). We examined seizure timing among subjects with different epilepsy types, seizure types, epilepsy syndromes, and localization. We also examined the familial aggregation of sleep/wake occurrence of seizures. Results Seizures in nonacquired focal epilepsy (NAFE) were more likely to occur during sleep than seizures in generalized epilepsy (GE), for both convulsive (odds ratio [OR] 5.2, 95% confidence interval [CI] 3.59–7.52) and nonconvulsive seizures (OR 4.2, 95% CI 2.48–7.21). Seizures occurring within 1 h of awakening were more likely to occur in patients with GE than with NAFE for both convulsive (OR 2.3, 95% CI 1.54– 3.39) and nonconvulsive (OR 1.7, 95% CI 1.04–2.66) seizures. Frontal onset seizures were more likely than temporal onset seizures to occur during sleep. Sleep/wake timing of seizures in first-degree relatives predicted timing of seizures in the proband. Significance We found that sleep/wake timing of seizures is associated with both epilepsy syndrome and seizure type. In addition, we provide the first evidence for a genetic contribution to sleep/wake timing of seizures in a large group of individuals with common epilepsy syndromes. PMID:26948972

  13. Ictal scalp EEG recording during sleep and wakefulness: diagnostic implications for seizure localization and lateralization.

    PubMed

    Buechler, Robbie D; Rodriguez, Alcibiades J; Lahr, Brian D; So, Elson L

    2008-02-01

    To determine the localizing value of electroencephalography (EEG) for seizures during sleep versus seizures during wakefulness, we compared scalp EEG for 58 seizures that occurred during sleep with 76 seizures during wake in 28 consecutive patients with temporal lobe epilepsy. Regression analysis showed that seizures during sleep are 2.5 times more likely to have focal EEG onset (p = 0.01) and 4 times more likely to correctly localize seizure onset (p = 0.04) than seizures during wake. EEG seizure onset preceded clinical onset by a longer duration in sleep seizures (mean, 4.69 s) than in wake seizures (mean, 1.23 s; p < 0.01). Sleep seizures showed fewer artifacts, but the difference was not significant (p = 0.07). For temporal lobectomy candidates undergoing video-EEG monitoring, the recording of seizures during sleep may be favored.

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

    PubMed Central

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

    2014-01-01

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

  15. Epileptic Seizures From Abnormal Networks: Why Some Seizures Defy Predictability

    PubMed Central

    Azhar, Feraz; Kudela, Pawel; Bergey, Gregory K.; Franaszczuk, Piotr J.

    2011-01-01

    Summary Seizure prediction has proven to be difficult in clinically realistic environments. Is it possible that fluctuations in cortical firing could influence the onset of seizures in an ictal zone? To test this, we have now used neural network simulations in a computational model of cortex having a total of 65,536 neurons with intercellular wiring patterned after histological data. A spatially distributed Poisson driven background input representing the activity of neighboring cortex affected 1% of the neurons. Gamma distributions were fit to the interbursting phase intervals, a non-parametric test for randomness was applied, and a dynamical systems analysis was performed to search for period-1 orbits in the intervals. The non-parametric analysis suggests that intervals are being drawn at random from their underlying joint distribution and the dynamical systems analysis is consistent with a nondeterministic dynamical interpretation of the generation of bursting phases. These results imply that in a region of cortex with abnormal connectivity analogous to a seizure focus, it is possible to initiate seizure activity with fluctuations of input from the surrounding cortical regions. These findings suggest one possibility for ictal generation from abnormal focal epileptic networks. This mechanism additionally could help explain the difficulty in predicting partial seizures in some patients. PMID:22169211

  16. Single photon emission computed tomography in seizure disorders.

    PubMed Central

    Denays, R; Rubinstein, M; Ham, H; Piepsz, A; Noël, P

    1988-01-01

    Fourteen children with various seizure disorders were studied using a cerebral blood flow tracer, 123I iodoamphetamine (0.05 mCi/kg), and single photon emission computed tomography (SPECT). In the five patients with radiological lesions, SPECT showed congruent or more extensive abnormalities. Five of the nine children with a normal scan on computed tomography had abnormal SPECT studies consisting of focal hypoperfusion, diffuse hemispheric hypoperfusion, multifocal and bilateral hypoperfusion, or focal hyperperfusion. A focal lesion seen on SPECT has been found in children with tonic-clonic seizures suggesting secondarily generalised seizures. Moreover the pattern seen on SPECT seemed to be related to the clinical status. An extensive impairment found on SPECT was associated with a poor evolution in terms of intellectual performance and seizure frequency. Conversely all children with a normal result on SPECT had less than two seizures per year and normal neurological and intellectual development. Images Figure PMID:3264135

  17. Aberrant hippocampal neurogenesis after limbic kindling: Relationship to BDNF and hippocampal-dependent memory.

    PubMed

    Botterill, J J; Brymer, K J; Caruncho, H J; Kalynchuk, L E

    2015-06-01

    Seizures dramatically increase the number of adult generated neurons in the hippocampus. However, it is not known whether this effect depends on seizures that originate in specific brain regions or whether it is nonspecific to seizure activity regardless of origin. We used kindling of different brain sites to address this question. Rats received 99 kindling stimulations of the basolateral amygdala, dorsal hippocampus, or caudate nucleus over a 6-week period. After kindling, we counted the number of adult generated hippocampal neurons that were birth-dated with the proliferative marker bromodeoxyuridine (BrdU) to evaluate cell proliferation and survival under conditions of repeated seizures. Next, we counted the number of doublecortin immunoreactive (DCX-ir) cells and evaluated their dendritic complexity to determine if limbic and nonlimbic seizures have differential effects on neuronal maturation. We also quantified hippocampal brain-derived neurotrophin factor (BDNF) protein levels using an ELISA kit and assessed memory performance using a hippocampal-dependent fear conditioning paradigm. We found that limbic, but not nonlimbic, seizures dramatically increased hippocampal cell proliferation and the number of hilar-CA3 ectopic granule cells. Further, limbic kindling promoted dendritic outgrowth of DCX-ir cells and the number of DCX-ir cells containing basal dendrites. Limbic kindling also enhanced BDNF protein levels throughout the entire hippocampus and impaired the retrieval of fear memories. Collectively, our results suggest a relationship between limbic seizures, neurogenesis, BDNF protein, and cognition.

  18. 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.

  19. The effects of glycemic control on seizures and seizure-induced excitotoxic cell death

    PubMed Central

    2012-01-01

    Background Epilepsy is the most common neurological disorder after stroke, affecting more than 50 million persons worldwide. Metabolic disturbances are often associated with epileptic seizures, but the pathogenesis of this relationship is poorly understood. It is known that seizures result in altered glucose metabolism, the reduction of intracellular energy metabolites such as ATP, ADP and phosphocreatine and the accumulation of metabolic intermediates, such as lactate and adenosine. In particular, it has been suggested that the duration and extent of glucose dysregulation may be a predictor of the pathological outcome of status. However, little is known about neither the effects of glycemic control on brain metabolism nor the effects of managing systemic glucose concentrations in epilepsy. Results In this study, we examined glycemic modulation of kainate-induced seizure sensitivity and its neuropathological consequences. To investigate the relationship between glycemic modulation, seizure susceptibility and its neuropathological consequences, C57BL/6 mice (excitotoxin cell death resistant) were subjected to hypoglycemia or hyperglycemia, followed by systemic administration of kainic acid to induce seizures. Glycemic modulation resulted in minimal consequences with regard to seizure severity but increased hippocampal pathology, irrespective of whether mice were hypoglycemic or hyperglycemic prior to kainate administration. Moreover, we found that exogenous administration of glucose following kainic acid seizures significantly reduced the extent of hippocampal pathology in FVB/N mice (excitotoxin cell death susceptible) following systemic administration of kainic acid. Conclusion These findings demonstrate that modulation of the glycemic index can modify the outcome of brain injury in the kainate model of seizure induction. Moreover, modulation of the glycemic index through glucose rescue greatly diminishes the extent of seizure-induced cell death following kainate

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

    PubMed

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

    2017-04-01

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

  1. 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 ...

  2. Remembering preservation in hippocampal amnesia

    PubMed Central

    Clark, Ian A.; Maguire, Eleanor A.

    2017-01-01

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

  3. Cyclosporin A acute encephalopathy and seizure syndrome in childhood: clinical features and risk of seizure recurrence.

    PubMed

    Gleeson, J G; duPlessis, A J; Barnes, P D; Riviello, J J

    1998-07-01

    Cyclosporin A is associated with an acute encephalopathy including seizures and alterations in mental status, herein referred to as cyclosporin A acute encephalopathy and seizure syndrome. The clinical history, electroencephalogram (EEG), and neuroimaging findings in 19 children with cyclosporin A acute encephalopathy and seizure syndrome over a 10-year period were reviewed in order to delineate clinical characteristics, imaging features, and to determine the risk of seizure recurrence in this population. All 19 had motor seizures associated with other features of cortical and subcortical dysfunction. The acute mean cyclosporin A level was 342 microg/L, but was within the "therapeutic" range in five cases. Brain imaging by computed tomography (CT) or magnetic resonance imaging (MRI) in the acute or subacute phase revealed lesions characteristic of cyclosporin A toxicity in 14 cases. Acute EEG abnormalities were present in all and included epileptiform discharges or focal slowing. Patients were followed for a median of 49 months (1-9 years). Follow-up imaging (n = 10) showed lesion resolution or improvement in the majority while EEG (n = 10) had normalized in only three. Seizures recurred in six patients and only in those with persistent EEG or imaging abnormalities. No patient had a second episode of cyclosporin A associated neurotoxicity or seizure. It appears that a significant risk of seizure recurrence exists following cyclosporin A acute encephalopathy and seizure syndrome and primarily in those children with persistent EEG or imaging abnormalities.

  4. Low distribution of synaptic vesicle protein 2A and synaptotagimin-1 in the cerebral cortex and hippocampus of spontaneously epileptic rats exhibiting both tonic convulsion and absence seizure.

    PubMed

    Hanaya, R; Hosoyama, H; Sugata, S; Tokudome, M; Hirano, H; Tokimura, H; Kurisu, K; Serikawa, T; Sasa, M; Arita, K

    2012-09-27

    The spontaneously epileptic rat (SER) is a double mutant (zi/zi, tm/tm) which begins to exhibit tonic convulsions and absence seizures after 6 weeks of age, and repetitive tonic seizures over time induce sclerosis-like changes in SER hippocampus with high brain-derived neurotrophic factor (BDNF) expression. Levetiracetam, which binds to synaptic vesicle protein 2A (SV2A), inhibited both tonic convulsions and absence seizures in SERs. We studied SER brains histologically and immunohistochemically after verification by electroencephalography (EEG), as SERs exhibit seizure-related alterations in the cerebral cortex and hippocampus. SERs did not show interictal abnormal spikes and slow waves typical of focal epilepsy or symptomatic generalized epilepsy. The difference in neuronal density of the cerebral cortex was insignificant between SER and Wistar rats, and apoptotic neurons did not appear in SERs. BDNF distributions portrayed higher values in the entorhinal and piriform cortices which would relate with hippocampal sclerosis-like changes. Similar synaptophysin expression in the cerebral cortex and hippocampus was found in both animals. Low and diffuse SV2A distribution portrayed in the cerebral cortex and hippocampus of SERs was significantly less than that of all cerebral lobes and inner molecular layer (IML) of the dentate gyrus (DG) of Wistar rats. The extent of low SV2A expression/distribution in SERs was particularly remarkable in the frontal (51% of control) and entorhinal cortices (47%). Lower synaptotagmin-1 expression (vs Wistar rats) was located in the frontal (31%), piriform (13%) and entorhinal (39%) cortices, and IML of the DG (38%) in SER. Focal low distribution of synaptotagmin-1 accompanying low SV2A expression may contribute to epileptogenesis and seizure propagation in SER.

  5. 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…

  6. Can Seizure-Alert Dogs predict seizures?

    PubMed

    Brown, Stephen W; Goldstein, Laura H

    2011-12-01

    An index observation where a dog was trained to alert to, as well as respond to, human tonic-clonic seizures led to further research and refinement of training techniques. This was followed by anecdotal reports of pet dogs spontaneously anticipating human epileptic seizures. An industry has since developed training Seizure-Alert Dogs (SADs) to give humans warnings of their seizures. In some cases this has been accompanied by a reduction in seizure frequency. SADs may be trained along with the person with epilepsy, responding specifically to that person's seizures, or may be trained separately. Recent sceptical reports of non-epileptic seizures in some people with SADs have cast doubt on dogs' ability to anticipate true epileptic seizures. This may reflect selection criteria for training programmes as well as training methods used, but does not necessarily indicate that SADs might not be able to predict epileptic seizures. Whether the seizures are epileptic or non-epileptic, it is speculated that SADs probably alert to subtle pre-ictal human behaviour changes, but may also be sensitive to heart rate or olfactory cues. As yet, however, no rigorous data exist as to whether seizure prediction by SADS is better than chance, and what false positive and negative prediction rates might be.

  7. 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

  8. Seizure-induced reduction in PIP3 levels contributes to seizure-activity and is rescued by valproic acid☆

    PubMed Central

    Chang, Pishan; Walker, Matthew C.; Williams, Robin S.B.

    2014-01-01

    Phosphatidylinositol (3–5) trisphosphate (PIP3) is a central regulator of diverse neuronal functions that are critical for seizure progression, however its role in seizures is unclear. We have recently hypothesised that valproic acid (VPA), one of the most commonly used drugs for the treatment of epilepsy, may target PIP3 signalling as a therapeutic mode of action. Here, we show that seizure induction using kainic acid in a rat in vivo epilepsy model resulted in a decrease in hippocampal PIP3 levels and reduced protein kinase B (PKB/AKT) phosphorylation, measured using ELISA mass assays and Western blot analysis, and both changes were restored following VPA treatment. These finding were reproduced in cultured rat hippocampal primary neurons and entorhinal cortex–hippocampal slices during exposure to the GABA(A) receptor antagonist pentylenetetrazol (PTZ), which is widely used to generate seizures and seizure-like (paroxysmal) activity. Moreover, VPA's effect on paroxysmal activity in the PTZ slice model is blocked by phosphatidylinositol 3-kinase (PI3K) inhibition or PIP2 sequestration by neomycin, indicating that VPA's efficacy is dependent upon PIP3 signalling. PIP3 depletion following PTZ treatment may also provide a positive feedback loop, since enhancing PIP3 depletion increases, and conversely, reducing PIP3 dephosphorylation reduces paroxysmal activity and this effect is dependent upon AMPA receptor activation. Our results therefore indicate that PIP3 depletion occurs with seizure activity, and that VPA functions to reverse these effects, providing a novel mechanism for VPA in epilepsy treatment. PMID:24148856

  9. 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

  10. Therapeutic epilepsy research: from pharmacological rationale to focal adenosine augmentation

    PubMed Central

    Boison, Detlev; Stewart, Kerry-Ann

    2009-01-01

    Epilepsy is a common seizure disorder affecting approximately 70 million people worldwide. Current pharmacotherapy is neuron-centered, frequently accompanied by intolerable side-effects, and fails to be effective in about one third of patients. Therefore, new therapeutic concepts are needed. Recent research suggests an astrocytic basis of epilepsy, presenting the possibility of novel therapeutic targets. In particular, dysfunction of the astrocyte-controlled, endogenous, adenosine-based seizure control system of the brain is implicated in seizure generation. Thus, astrogliosis – a pathological hallmark of the epileptic brain – is associated with upregulation of the adenosine-removing enzyme adenosine kinase (ADK), resulting in focal adenosine deficiency. Both astrogliotic upregulation of ADK in epilepsy and transgenic overexpression of ADK are associated with seizures, and inhibition of ADK prevents seizures in a mouse model of pharmacoresistant epilepsy. These findings link adenosine deficiency with seizures and predict that adenosine augmentation therapies (AATs) will likely be effective in preventing seizures. Given the widespread systemic and central side effects of systemically administered AATs, focal AATs (i.e., limited to the astrogliotic lesion) are a necessity. This Commentary will discuss the pharmacological rationale for the development of focal AATs. Additionally, several AAT strategies will be discussed: (1) adenosine released from silk-based brain implants; (2) adenosine released from locally implanted encapsulated cells; (3) adenosine released from stem cell-derived brain implants; and (4) adenosine augmenting gene therapies. Finally, new developments and therapeutic challenges in using focal AATs for epilepsy therapy will critically be evaluated. PMID:19682439

  11. Altered expression of adrenocorticotropic hormone in the epileptic gerbil hippocampus following spontaneous seizure.

    PubMed

    Oh, Yun-Jung; Kim, Heung-No; Jeong, Ji-Heon; Park, Dae-Kyoon; Park, Kyung-Ho; Ko, Jeong-Sik; Kim, Duk-Soo

    2013-02-01

    We investigated the temporal alterations of adrenocorticotropic hormone (ACTH) immunoreactivity in the hippocampus after seizure onset. Expression of ACTH was observed within interneurons in the pre-seizure group of seizure sensitive gerbils, whereas its immunoreactivities were rarely detected in seizure resistant gerbil. Three hr after the seizure, ACTH immunoreactivity was significantly increased in interneurons within all hippocampal regions. On the basis of their localization and morphology through immunofluorescence staining, these cells were identified as GABAA α1-containing interneurons. At the 12 hr postictal period, ACTH expression in these regions was down-regulated, in a similar manner to the pre-seizure group of gerbils. These findings support the increase in ACTH synthesis that contributes to a reduction of corticotrophin-releasing factor via the negative feedback system which in turn provides an opportunity to enhance the excitability of GABAergic interneurons. Therefore, ACTH may play an important role in the reduction of excitotoxicity in all hippocampal regions.

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

    PubMed

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

    2015-09-01

    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 months-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.

  13. 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.

  14. 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.

  15. Grand Mal Seizure

    MedlinePlus

    ... generalized tonic-clonic seizure — features a loss of consciousness and violent muscle contractions. It's the type of ... seizures have two stages: Tonic phase. Loss of consciousness occurs, and the muscles suddenly contract and cause ...

  16. Comparable seizure characteristics in magnetic seizure therapy and electroconvulsive therapy for major depression.

    PubMed

    Kayser, Sarah; Bewernick, Bettina H; Hurlemann, René; Soehle, Martin; Schlaepfer, Thomas E

    2013-11-01

    Electroconvulsive therapy (ECT) is highly effective for treatment-resistant depression (TRD); however, its use for less severe forms of depression is somewhat limited by a lack of control over current spreading to medial temporal lobe memory structures, resulting in various cognitive side effects. In contrast, magnetic seizure therapy (MST), which uses high frequency repetitive transcranial magnetic stimulation (rTMS) for local seizure induction, has been associated with reduced cognitive side effects. To assess whether different characteristics of seizures induced by both methods are responsible for the differences in neuropsychological side-effect profile, we studied seven TRD-patients undergoing both MST and ECT in an open-label, within subject, controlled crossover pilot study. Comparison parameters included seizure-related ictal characteristics, including motor activity, electromyogram (EMG), electroencephalogram (EEG), and postictal recovery and reorientation times.Our results showed no differences in motor activity or EMG and EEG characteristics, thus implicating similar electrophysiological processes in seizure induction with MST and ECT. In line with previous studies, we observed shorter postictal recovery and reorientation times following MST.The ictal characteristics of induced seizures were found similar with ECT and MST suggesting that the more focal seizure induction associated with MST may account for the more beneficial neuropsychological side effect profile of MST.

  17. 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

  18. 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

  19. Febrile Seizure: Demographic Features and Causative Factors

    PubMed Central

    ESMAILI GOURABI, Hamed; BIDABADI, Elham; CHERAGHALIPOUR, Fatemeh; AARABI, Yasaman; SALAMAT, Fatemeh

    2012-01-01

    Objective Because of geographical and periodical variation, we prompted to determine the demographic features and causative factors for febrile seizure in Rasht. Materials & Methods In this cross-sectional study, all 6–month- to 6-year-old children with the diagnosis of febrile seizure admitted to 17 Shahrivar hospital in Rasht, from August, 2009 to August, 2010 were studied. Age, sex, family history of the disease, seizure types, body temperature upon admission and infectious causes of the fever were recorded. All statistical analysis was performed with SPSS software, version 16. Results Of the 214 children (mean age, 25.24±15.40 months), 124 were boys and 109 had a positive family history. Complex seizures were seen in 39 cases. In patients with a complex febrile seizure, 59% had the repetitive type, 20.5% had the focal type and 20.5% had more than 15 minutes duration of seizures. Most of the repetitive seizures (78.3%) occurred in patients under 2 years old; the difference between under and over 2-year-old patients was statistically significant. Study results did not show significant differences between the two genders for simple or complex seizures. The mean body temperature upon admission was 38.2±1.32◦C (38.31±0.82 degrees in boys and 38.04±1.78 in girls). Upper respiratory infections were seen in most patients (74.29%). All cases of lower respiratory infections were boys. There was a statistically significant difference between boys and girls in causes of fever. Conclusion Most of the children had a positive family history and the most common causative factor was upper respiratory infection. PMID:24665278

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

    PubMed

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

    2012-01-01

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

  1. Focal status epilepticus as atypical presentation of pyridoxine-dependent epilepsy.

    PubMed

    Yoshii, Akira; Takeoka, Masanori; Kelly, Peter J; Krishnamoorthy, Kalpahty S

    2005-08-01

    Pyridoxine-dependent epilepsy usually presents in the neonatal period or even in utero, is refractory to antiepileptic medications, and is treatable with lifelong administration of pyridoxine. The seizures are typically generalized tonic-clonic, although myoclonic seizures or infantile spasms have been described. We report an infant who presented at 5 months of age with a right-sided clonic seizure with fever. Subsequently, she had recurrent right focal or generalized seizures despite sequential treatment with various antiepileptic medications. At 7 months, she was hospitalized with status epilepticus, which was finally controlled with pyridoxine. After she became seizure free, she continued to have a strong left arm preference with mild weakness of the right arm and delayed language skill. Eventually, she outgrew these symptoms. This case illustrates that pyridoxine-dependent epilepsy, although rare, must be included in the differential diagnosis of focal seizures, especially when the seizures are refractory to traditional antiepileptic drugs.

  2. 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.

  3. Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology.

    PubMed

    Fisher, Robert S; Cross, J Helen; French, Jacqueline A; Higurashi, Norimichi; Hirsch, Edouard; Jansen, Floor E; Lagae, Lieven; Moshé, Solomon L; Peltola, Jukka; Roulet Perez, Eliane; Scheffer, Ingrid E; Zuberi, Sameer M

    2017-04-01

    The International League Against Epilepsy (ILAE) presents a revised operational classification of seizure types. The purpose of such a revision is to recognize that some seizure types can have either a focal or generalized onset, to allow classification when the onset is unobserved, to include some missing seizure types, and to adopt more transparent names. Because current knowledge is insufficient to form a scientifically based classification, the 2017 Classification is operational (practical) and based on the 1981 Classification, extended in 2010. Changes include the following: (1) "partial" becomes "focal"; (2) awareness is used as a classifier of focal seizures; (3) the terms dyscognitive, simple partial, complex partial, psychic, and secondarily generalized are eliminated; (4) new focal seizure types include automatisms, behavior arrest, hyperkinetic, autonomic, cognitive, and emotional; (5) atonic, clonic, epileptic spasms, myoclonic, and tonic seizures can be of either focal or generalized onset; (6) focal to bilateral tonic-clonic seizure replaces secondarily generalized seizure; (7) new generalized seizure types are absence with eyelid myoclonia, myoclonic absence, myoclonic-atonic, myoclonic-tonic-clonic; and (8) seizures of unknown onset may have features that can still be classified. The new classification does not represent a fundamental change, but allows greater flexibility and transparency in naming seizure types.

  4. Time-frequency analysis of intracranial EEG in patients with myoclonic seizures.

    PubMed

    Sun, Ying; Zhang, Guojun; Zhang, Xiaohua; Yan, Xiaoming; Li, Liping; Xu, Cuiping; Yu, Tao; Liu, Chunyan; Zhu, Yu; Lin, Yicong; Wang, Yuping

    2016-12-01

    Myoclonic seizures are defined as generalized seizures according to the classification of seizure by the International League Against Epilepsy (ILAE). The pathogenesis of myoclonic seizures is not yet clear. There are very few studies on the focal surgical treatment of myoclonic seizures. The aim of this study is to investigate the characteristics of myoclonic seizure onset in different bands of the intracranial electroencephalogram (EEG) and their dynamic changes in temporal and spatial evolution. We studied four patients with myoclonic seizures who were under the focal resection of the epileptogenic zone. We retrospectively analyzed the semiology, electrocorticogram (ECoG) and imaging data of these patients, and conducted time-frequency analysis of broadband ECoG activity. We found that myoclonic seizures without clinical lateralizing signs could be improved by the resection of the epileptogenic zone. The ECoG power in different frequency bands increased to a peak at 0.5s before the clinical seizure onset and decreased quickly afterwards. The power of alpha activity was highest during the preictal and ictal periods. The central zone had higher power than the epileptogenic zone in all frequency bands during the preictal period, but this difference was not statistically significant. Our results suggest that myoclonic seizures in some patients might have a focal origination, with a fast bilateral propagating network in all frequency bands, especially the alpha band.

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

    PubMed

    Schmidt, Dieter

    2011-02-01

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

  6. Features and futures: seizure detection in partial epilepsies.

    PubMed

    Han, Yu; Hsin, Yue-Loong; Harnod, Tomor; Liu, Wentai

    2011-10-01

    Many factors underlying basic epileptic conditions determine the characteristics of epileptic seizures and the therapeutic outcome. Diagnosis and treatment rely on the clinical manifestations as well as electroencephalographic (EEG) epileptic activities. This article briefly reviews the fundamentals of the EEG, interictal, and ictal electrical activities of both extracranial and intracranial EEG of partial epilepsies, based on the information obtained from epilepsy patients who have undergone epilepsy surgery. The authors also present the status of their current research, focusing on decomposed seizure sources and the rendered spatial-temporal transitions in focal seizure.

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

    PubMed

    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.

  8. 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.

  9. Athletes with seizure disorders.

    PubMed

    Knowles, Byron Don; Pleacher, Michael D

    2012-01-01

    Individuals with seizure disorders have long been restricted from participation in certain sporting activities. Those with seizure disorders are more likely than their peers to have a sedentary lifestyle and to develop obesity. Regular participation in physical activity can improve both physical and psychosocial outcomes for persons with seizure disorders. Seizure activity often is reduced among those patients who regularly engage in aerobic activity. Recent literature indicates that the diagnosis of seizure disorders remains highly stigmatizing in the adolescent population. Persons with seizure disorders may be more accepted by peer groups if they are allowed to participate in sports and recreational activities. Persons with seizure disorders are encouraged to participate in regular aerobic activities. They may participate in team sports and contact or collision activities provided that they utilize appropriate protective equipment. There seems to be no increased risk of injury or increasing seizure activity as the result of such participation. Persons with seizure disorders still are discouraged from participating in scuba diving and skydiving. The benefits of participation in regular sporting activity far outweigh any risk to the athlete with a seizure disorder who chooses to participate in sports.

  10. Forecasting seizures in dogs with naturally occurring epilepsy.

    PubMed

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

    2014-01-01

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

  11. Downregulated GABA and BDNF-TrkB pathway in chronic cyclothiazide seizure model.

    PubMed

    Kong, Shuzhen; Cheng, Zhihua; Liu, Jianhui; Wang, Yun

    2014-01-01

    Cyclothiazide (CTZ) has been reported to simultaneously enhance glutamate receptor excitation and inhibit GABAA receptor inhibition, and in turn it evokes epileptiform activities in hippocampal neurons. It has also been shown to acutely induce epileptic seizure behavior in freely moving rats. However, whether CTZ induced seizure rats could develop to have recurrent seizure still remains unknown. In the current study, we demonstrated that 46% of the CTZ induced seizure rats developed to have recurrent seizure behavior as well as epileptic EEG with a starting latency between 2 weeks and several months. In those chronic seizure rats 6 months after the seizure induction by the CTZ, our immunohistochemistry results showed that both GAD and GAT-1 were significantly decreased across CA1, CA3, and dentate gyrus area of the hippocampus studied. In addition, both BDNF and its receptor TrkB were also decreased in hippocampus of the chronic CTZ seizure rats. Our results indicate that CTZ induced seizure is capable of developing to have recurrent seizure, and the decreased GABA synthesis and transport as well as the impaired BDNF-TrkB signaling pathway may contribute to the development of the recurrent seizure. Thus, CTZ seizure rats may provide a novel animal model for epilepsy study and anticonvulsant drug testing in the future.

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

    PubMed

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

    2015-01-01

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

  13. Epileptic seizures as condensed sleep: an analysis of network dynamics from electroencephalogram signals.

    PubMed

    Gast, Heidemarie; Müller, Markus; Rummel, Christian; Roth, Corinne; Mathis, Johannes; Schindler, Kaspar; Bassetti, Claudio L

    2014-06-01

    Both deepening sleep and evolving epileptic seizures are associated with increasing slow-wave activity. Larger-scale functional networks derived from electroencephalogram indicate that in both transitions dramatic changes of communication between brain areas occur. During seizures these changes seem to be 'condensed', because they evolve more rapidly than during deepening sleep. Here we set out to assess quantitatively functional network dynamics derived from electroencephalogram signals during seizures and normal sleep. Functional networks were derived from electroencephalogram signals from wakefulness, light and deep sleep of 12 volunteers, and from pre-seizure, seizure and post-seizure time periods of 10 patients suffering from focal onset pharmaco-resistant epilepsy. Nodes of the functional network represented electrical signals recorded by single electrodes and were linked if there was non-random cross-correlation between the two corresponding electroencephalogram signals. Network dynamics were then characterized by the evolution of global efficiency, which measures ease of information transmission. Global efficiency was compared with relative delta power. Global efficiency significantly decreased both between light and deep sleep, and between pre-seizure, seizure and post-seizure time periods. The decrease of global efficiency was due to a loss of functional links. While global efficiency decreased significantly, relative delta power increased except between the time periods wakefulness and light sleep, and pre-seizure and seizure. Our results demonstrate that both epileptic seizures and deepening sleep are characterized by dramatic fragmentation of larger-scale functional networks, and further support the similarities between sleep and seizures.

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

    PubMed

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

    2016-10-01

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

  15. Monitoring neonatal seizures.

    PubMed

    Boylan, Geraldine B; Stevenson, Nathan J; Vanhatalo, Sampsa

    2013-08-01

    Neonatal seizures are a neurological emergency and prompt treatment is required. Seizure burden in neonates can be very high, status epilepticus a frequent occurrence, and the majority of seizures do not have any clinical correlate. Detection of neonatal seizures is only possible with continuous electroencephalogram (EEG) monitoring. EEG interpretation requires special expertise that is not available in most neonatal intensive care units (NICUs). As a result, a simplified method of EEG recording incorporating an easy-to-interpret compressed trend of the EEG output (amplitude integrated EEG) from one of the EEG output from one or two channels has emerged as a popular way to monitor neurological function in the NICU. This is not without limitations; short duration and low amplitude seizures can be missed, artefacts are problematic and may mimic seizure-like activity and only a restricted area of the brain is monitored. Continuous multichannel EEG is the gold standard for detecting seizures and monitoring response to therapy but expert interpretation of the EEG output is generally not available. Some centres have set up remote access for neurophysiologists to the cot-side EEG, but reliable interpretation is wholly dependent on the 24 h availability of experts, an expensive solution. A more practical solution for the NICU without such expertise is an automated seizure detection system. This review outlines the current state of the art regarding cot-side monitoring of neonatal seizures in the NICU.

  16. Gelastic seizures due to right temporal cortical dysplasia.

    PubMed

    Dericioglu, Nese; Cataltepe, Oguz; Tezel, Gaye Guler; Saygi, Serap

    2005-06-01

    Gelastic seizures are an uncommon seizure type. They are most frequently observed in patients with hypothalamic hamartoma. Their association with other types of cerebral lesions is rare. Depending on the location of the lesion, gelastic seizures may or may not be accompanied by a subjective feeling of mirth. The pathophysiological mechanisms of this type of seizure are still undefined, and little is known about which pathways promote laughter and its emotional content, mirth. We present a young man with drug-resistant, gelastic seizures due to focal cortical dysplasia of the right inferior temporal gyrus. The lesion was evident on cranial MRI. Interictal EEG displayed a right temporal focus, whereas ictal EEG was not informative. Ictal loss of consciousness precluded reporting of any possible emotional experience. The patient underwent surgical resection of the lesion and has been seizure-free with anti-epileptic medication for two years. Although various anatomical regions may elicit laughter, in view of the current literature it seems that the anterior cingulate region is involved in the motor aspects of laughter, while the basal temporal cortex is involved in the processing of mirth. The fact that the present case exhibited gelastic seizures stresses once more the importance of the baso-lateral temporal cortex in the genesis of this type of seizures.[Published with video sequences].

  17. Seizures in a Pediatric Intensive Care Unit: A Prospective Study

    PubMed Central

    Yazici, Mutlu Uysal; Ayar, Ganime; Karalok, Zeynep Selen; Arhan, Ebru Petek

    2016-01-01

    Background: The aim of the research is to determine the etiology and clinical features of seizures in critically ill children admitted to a pediatric intensive care unit (PICU). Methods: A total of 203 children were admitted from June 2013 to November 2013; 45 patients were eligible. Age ranged from 2 months to 19 years. Seizures were organized as epileptic or acute symptomatic. Pediatric risk of mortality score III, Glasgow coma scale, risk factors, coexistent diagnosis, medications administered before admission, type and duration of seizures, drugs used, requirement and duration of mechanical ventilation, length of stay and neuroimaging findings were collected as demographic data prospectively. Results: The male–female ratio was 0.8. Mean age was 5.4. The most common causes of seizures were acute symptomatic. Most frequent coexistent diagnosis was infectious diseases, and 53.3% had recurrent seizures. Medications were administered to 51.1% of the patients before admission. Seizures were focal in 21 (46.7%), generalized in 11 (24.4%) and 13 (28.9%) had status epilepticus. Intravenous midazolam was first-line therapy in 48.9%. Acute symptomatic seizures were usually new-onset, and duration was shorter. Epileptic seizures tended to be recurrent and were likely to progress to status epilepticus. However, type of seizures did not change severity of the disease. Also, laboratory test results, medications administered before admission, requirement and duration of ventilation, mortality and length of stay were not significant between epileptic/acute symptomatic patients. Conclusion: Seizures in critically ill children, which may evolve into status epilepticus, is an important condition that requires attention regardless of cause. Intensified educational programs for PICU physicians and international guidelines are necessary for a more efficient approach to children with seizures. PMID:26892503

  18. 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…

  19. 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…

  20. Carbamazepine clearance and seizure stability during pregnancy.

    PubMed

    Johnson, Emily L; Stowe, Zachary N; Ritchie, James C; Newport, D Jeffrey; Newman, Melanee L; Knight, Bettina; Pennell, Page B

    2014-04-01

    The aims of this study were to characterize the alterations in total and free carbamazepine (CBZ) and in total and free carbamazepine-epoxide (CBZ-EPO) clearances during pregnancy, to calculate the change in free fractions of CBZ and CBZ-EPO during pregnancy, and to determine whether seizure worsening is associated with a low ratio to nonpregnant baseline concentration of total or free CBZ or CBZ-EPO. Women on CBZ were enrolled before conception or during pregnancy in this prospective, observational study. Concomitant medications and seizure frequency were recorded. Serum total and free CBZ and CBZ-EPO were collected at each visit. Changes in the clearance of all four compounds and free fractions of CBZ and CBZ-EPO were compared with nonpregnant baseline. During pregnancy, the ratios to baseline concentrations of total and free CBZ and CBZ-EPO were compared for months with and without increased seizure frequency. Total and free CBZ and CBZ-EPO clearances were calculated in 15 pregnancies in 12 women. Clearances did not change for any of these compounds during pregnancy. The free fraction of CBZ increased from 0.23 at baseline to a maximum of 0.32 in the third trimester (p=0.008). In the six women on CBZ monotherapy with adequate seizure diaries and blood sampling, seizure worsening did not correspond to a ratio to baseline concentration of less than 0.65 for total or free CBZ or CBZ-EPO. In conclusion, total and free CBZ and CBZ-EPO clearances did not change substantially during pregnancy, and seizure frequency worsening was not associated with decreased concentrations of total or free CBZ; therefore, therapeutic drug monitoring may not be necessary for all women on CBZ during pregnancy. Further studies with larger sample sizes are needed before definitive recommendations can be made. Carbamazepine monotherapy may be a relatively safe and cost effective treatment option for women with focal epilepsy syndromes during pregnancy.

  1. 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

  2. Cardiac arrhythmias during or after epileptic seizures.

    PubMed

    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.

  3. Chronic exercise dampens hippocampal glutamate overflow induced by kainic acid in rats.

    PubMed

    Holmes, Philip V; Reiss, Jenny I; Murray, Patrick S; Dishman, Rod K; Spradley, Jessica M

    2015-05-01

    Our laboratory has previously reported that chronic, voluntary exercise diminishes seizure-related behaviors induced by convulsant doses of kainic acid. The present experiments tested the hypothesis that exercise exerts this protective effect through a mechanism involving suppression of glutamate release in the hippocampal formation. Following three weeks of voluntary wheel running or sedentary conditions, rats were injected with 10 mg/kg of kainic acid, and hippocampal glutamate was measured in real time using a telemetric, in vivo voltammetry system. A separate experiment measured electroencephalographic (EEG) activity following kainic acid treatment. Results of the voltammetry experiment revealed that the rise in hippocampal glutamate induced by kainic acid is attenuated in exercising rats compared to sedentary controls, indicating that the exercise-induced protection against seizures involves regulation of hippocampal glutamate release. The findings reveal the potential benefit of regular exercise in the treatment and prevention of seizure disorders and suggest a possible neurobiological mechanism underlying this effect.

  4. 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.

  5. Is neuronal death required for seizure-induced epileptogenesis in the immature brain?

    PubMed Central

    Baram, Tallie Z.; Eghbal-Ahmadi, Mariam; Bender, Roland A.

    2011-01-01

    Do seizures cause neuronal death? At least in the immature hippocampus, this may not be the critical question for determining the mechanisms of epileptogenesis. Neuronal injury and death have clearly been shown to occur in most epilepsy models in the mature brain, and are widely considered a prerequisite to seizure-induced epilepsy. In contrast, little neuronal death occurs after even a severe and prolonged seizure prior to the third postnatal week. However, seizures early in life, for example prolonged experimental febrile seizures, can profoundly and permanently change the hippocampal circuit in a pro-epileptogenic direction. These seizure-induced alterations of limbic excitability may require transient structural injury, but are mainly due to functional changes in expression of gene coding for specific receptors and channels, leading to altered functional properties of hippocampal neurons. Thus, in some pro-epileptogenic models in the developing brain, neither the death of neurons nor death-induced abnormalities of surviving neurons may underlie the formation of an epileptic circuit. Rather, findings in the experimental prolonged febrile seizure model suggest that persistent functional alterations of gene expression (‘neuroplasticity’) in diverse hippocampal neuronal populations may promote pro-epileptogenic processes induced by these seizures. These findings also suggest that during development, relatively short, intense bursts of neuronal activity may disrupt ‘normal’ programmed maturational processes to result in permanent, selective alterations of gene expression, with profound functional consequences. Therefore, determining the cascade of changes in the programmed expression of pertinent genes, including their temporal and cell-specific spatial profiles, may provide important information for understanding the process of transformation of an evolving, maturing hippocampal network into one which is hyperexcitable. PMID:12143355

  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. Pulmonary edema following generalized tonic clonic seizures is directly associated with seizure duration

    PubMed Central

    Kennedy, Jeffrey D.; Hardin, Kimberly A.; Parikh, Palak; Li, Chin-Shang; Seyal, Masud

    2015-01-01

    Purpose Postictal pulmonary edema (PPE) is almost invariably present in human and animal cases of sudden unexpected death in epilepsy (SUDEP) coming to autopsy. PPE may be a contributing factor in SUDEP. The incidence of postictal PPE is unknown. We retrospectively investigated PPE following generalized tonic clonic seizures (GTCS) in the epilepsy monitoring unit. Methods Chest X-Rays (CXR) following each GTCS were obtained in 24 consecutive patients. Relationship of CXR abnormality to seizure duration, ictal/postictal oxygen desaturation (SpO2), apnea and presence of postictal generalized EEG suppression (PGES) was investigated using logistic regression. Results Eleven of 24 patients had CXR abnormalities following a GTCS. In these 11 patients, 22 CXR were obtained and abnormalities were present in 15 CXR. Abnormalities included PPE in 7 patients, of which 2 also had focal infiltrates. In 4 patients focal infiltrates were present without PPE. There was no significant difference in mean time to CXR (225 min) following GTCS in the abnormal CXR group versus the normal group of patients (196 min). Mean preceding seizure duration was longer (p=0.002) in GTCS with abnormal CXR (259.7 sec) versus GTCS with normal CXR (101.2 sec). Odds-ratio for CXR abnormality was 20.46 (p=0.006) with seizure duration greater than 100 sec versus less than 100 sec. On multivariable analysis, only the seizure duration was a significant predictor of CXR abnormality (p=0.015). Conclusions Radiographic abnormalities are not uncommon following GTCS. The presence of CXR abnormality is significantly associated with the duration of the preceding GTCS. Severe, untreated PPE may be relevant to the pathophysiology of SUDEP. PMID:25844030

  8. Seizures Following Cardiopulmonary Bypass

    PubMed Central

    Brouwer, Monique E.; McMeniman, William J.

    2016-01-01

    Abstract: Seizures following cardiopulmonary bypass are an immediate and alarming indication that a neurologic event has occurred. A case report of a 67-year-old man undergoing aortic valve surgery who unexpectedly experiences seizures following cardiopulmonary bypass is outlined. Possible contributing factors including atheromatous disease in the aorta, low cerebral perfusion pressures, an open-chamber procedure, and the use of tranexamic acid are identified. PMID:27729707

  9. 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.

  10. Regional and global connectivity disturbances in focal epilepsy, related neurocognitive sequelae, and potential mechanistic underpinnings.

    PubMed

    Englot, Dario J; Konrad, Peter E; Morgan, Victoria L

    2016-10-01

    Epilepsy is among the most common brain network disorders, and it is associated with substantial morbidity and increased mortality. Although focal epilepsy was traditionally considered a regional brain disorder, growing evidence has demonstrated widespread network alterations in this disorder that extend beyond the epileptogenic zone from which seizures originate. The goal of this review is to summarize recent investigations examining functional and structural connectivity alterations in focal epilepsy, including neuroimaging and electrophysiologic studies utilizing model-based or data-driven analytic methods. A significant subset of studies in both mesial temporal lobe epilepsy and focal neocortical epilepsy have demonstrated patterns of increased connectivity related to the epileptogenic zone, coupled with decreased connectivity in widespread distal networks. Connectivity patterns appear to be related to the duration and severity of disease, suggesting progressive connectivity reorganization in the setting of recurrent seizures over time. Global resting-state connectivity disturbances in focal epilepsy have been linked to neurocognitive problems, including memory and language disturbances. Although it is possible that increased connectivity in a particular brain region may enhance the propensity for seizure generation, it is not clear if global reductions in connectivity represent the damaging consequences of recurrent seizures, or an adaptive mechanism to prevent seizure propagation away from the epileptogenic zone. Overall, studying the connectome in focal epilepsy is a critical endeavor that may lead to improved strategies for epileptogenic-zone localization, surgical outcome prediction, and a better understanding of the neuropsychological implications of recurrent seizures.

  11. Consciousness of seizures and consciousness during seizures: are they related?

    PubMed

    Detyniecki, Kamil; Blumenfeld, Hal

    2014-01-01

    Recent advances have been made in the network mechanisms underlying impairment of consciousness during seizures. However, less is known about patient awareness of their own seizures. Studying patient reports or documentation of their seizures is currently the most commonly utilized mechanism to scientifically measure patient awareness of seizures. The purpose of this review is to summarize the available evidence regarding the accuracy of patient seizure counts and identify the variables that may influence unreliable seizure reporting. Several groups looking at patient documentation of seizures during continuous EEG monitoring show that patients do not report as many as 50% of their seizures. These studies also suggest that seizures accompanied by loss of consciousness, arising from the left hemisphere or the temporal lobe, or occurring during sleep are associated with significantly reduced reporting. Baseline memory performance does not appear to have a major influence on the accuracy of seizure report. Further prospective studies using validated ictal behavioral testing as well as using correlation with newer electrophysiological and neuroimaging techniques for seizure localization are needed to more fully understand the mechanisms of underreporting of seizures. Better methods to alert caregivers about unrecognized seizures and to improve seizure documentation are under investigation.

  12. Bilaterally symmetric focal cortical dysplasia in a golden retriever dog.

    PubMed

    Casey, K M; Bollen, A W; Winger, K M; Vernau, K M; Dickinson, P J; Higgins, R J; Sisó, S

    2014-11-01

    A 10-year-old golden retriever dog was referred with a 24-h history of generalized seizures. Magnetic resonance imaging of the brain found no abnormalities on 3 mm transverse sections and the dog was subsequently humanely destroyed. Microscopically there was bilaterally symmetrical focal disorganization of cortical grey matter within the tips of the right and left suprasylvian gyri of the temporal cortex. The focal abnormal cortical lamination was characterized by loss of pyramidal neurons with abnormal, irregular, angular, remaining neurons occasionally forming clusters, surrounded by fibrillary astrogliosis and microgliosis and vascular proliferation. These histological findings are consistent with focal cortical dysplasia, a cerebral cortical malformation that causes seizures in people, but not reported previously in the dog.

  13. Gelastic seizures: A case of lateral frontal lobe epilepsy and review of the literature.

    PubMed

    Kovac, Stjepana; Deppe, Michael; Mohammadi, Siawoosh; Schiffbauer, Hagen; Schwindt, Wolfram; Möddel, Gabriel; Dogan, Mujgan; Evers, Stefan

    2009-06-01

    We describe a 40-year-old patient with gelastic seizures triggered by hand movement. Despite nonlesional magnetic resonance imaging (MRI), electroencephalography (EEG), functional magnetic resonance imaging (fMRI), and diffusion tensor imaging (DTI) are concordant with seizure onset in the right frontocentral area. Seizure semiology and EEG recordings imply involvement of mesial frontal structures remote from seizure initiation site. We reviewed all published cases on gelastic seizures of frontal lobe origin to find characteristic features. For further investigation of the phenomenon of movement-induced seizures, fMRI was performed using a finger tapping paradigm. Interictal fMRI revealed widespread activation of right motor cortex during finger tapping on either side outreaching the anatomical representation of the left finger. In line with this finding DTI revealed fiber track impairment in the right frontocentral region, supporting the hypothesis of a focal derangement. This case highlights the importance of complementary functional investigations in MRI-negative epilepsies.

  14. Cortical deactivation induced by subcortical network dysfunction in limbic seizures

    PubMed Central

    Englot, Dario J.; Modi, Badri; Mishra, Asht M.; DeSalvo, Matthew; Hyder, Fahmeed; Blumenfeld, Hal

    2009-01-01

    Normal human consciousness may be impaired by two possible routes: direct reduced function in widespread cortical regions, or indirect disruption of subcortical activating systems. The route through which temporal lobe limbic seizures impair consciousness is not known. We recently developed an animal model which, like human limbic seizures, exhibits neocortical deactivation including cortical slow waves and reduced cortical cerebral blood flow (CBF). We now find through functional MRI (fMRI) that electrically-stimulated hippocampal seizures in rats cause increased activity in subcortical structures including the septal area and mediodorsal thalamus, along with reduced activity in frontal, cingulate, and retrosplenial cortex. Direct recordings from the hippocampus, septum, and medial thalamus demonstrated fast poly-spike activity associated with increased neuronal firing and CBF, while frontal cortex showed slow oscillations with decreased neuronal firing and CBF. Stimulation of septal area, but not hippocampus or medial thalamus, in the absence of a seizure resulted in cortical deactivation with slow oscillations and behavioral arrest, resembling changes seen during limbic seizures. Transecting the fornix, the major route from hippocampus to subcortical structures, abolished the negative cortical and behavioral effects of seizures. Cortical slow oscillations and behavioral arrest could be reconstituted in fornix-lesioned animals by inducing synchronous activity in the hippocampus and septal area, implying involvement of a downstream region converged upon by both structures. These findings suggest that limbic seizures may cause neocortical deactivation indirectly, through impaired subcortical function. If confirmed, subcortical networks may represent a target for therapies aimed at preserving consciousness in human temporal lobe seizures. PMID:19828814

  15. 10 Methylxanthines, seizures and excitotoxicity

    PubMed Central

    Boison, Detlev

    2010-01-01

    Clinical evidence, in particular the wide use of theophylline as bronchodilator, suggests that methylxanthines can cause seizures in patients without known underlying epilepsy. Theophylline is also known to be an added risk factor for seizure exacerbation in patients with epilepsy. The proconvulsant activity of methylxanthines can best be explained by antagonizing the brain’s own anticonvulsant adenosine. Recent evidence suggests that adenosine dysfunction is a pathological hallmark of epilepsy contributing to seizure generation and seizure spread. Conversely, adenosine augmentation therapies are effective in seizure suppression and prevention, whereas adenosine receptor antagonists such as methylxanthines generally exacerbate seizures. The impact of the methylxanthines caffeine and theophylline on seizures and excitotoxicity depends on timing, dose, and acute versus chronic use. New findings suggest a role of free radicals in theophylline-induced seizures and adenosine-independent mechanisms for seizure generation have been proposed. PMID:20859799

  16. 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.

  17. Focal Choroidal Excavation

    PubMed Central

    Cebeci, Zafer; Bayraktar, Şerife; Oray, Merih; Kır, Nur

    2016-01-01

    Focal choroidal excavation is a choroidal pit that can be detected by optical coherence tomography. Central serous chorioretinopathy, choroidal neovascularization and polypoidal choroidal vasculopathy are pathologies associated with focal choroidal excavation. In this article, we present the follow-up and treatment outcomes of three eyes of two patients with focal choroidal excavation. PMID:28050329

  18. Focal Choroidal Excavation.

    PubMed

    Cebeci, Zafer; Bayraktar, Şerife; Oray, Merih; Kır, Nur

    2016-12-01

    Focal choroidal excavation is a choroidal pit that can be detected by optical coherence tomography. Central serous chorioretinopathy, choroidal neovascularization and polypoidal choroidal vasculopathy are pathologies associated with focal choroidal excavation. In this article, we present the follow-up and treatment outcomes of three eyes of two patients with focal choroidal excavation.

  19. Hippocampal stroke.

    PubMed

    Szabo, Kristina

    2014-01-01

    The first to link disturbance of memory and lesions of the medial temporal lobe was the Russian neurologist von Bechterew, who in 1989 presented the brain of a 60-year-old man who had suffered from severe amnesia. Autopsy showed bilateral damage of the medial temporal lobe. Several following postmortem case studies confirmed the association between permanent amnesia and bitemporal stroke. Reports of transient memory deficits in unilateral stroke in combination with other neurological and neuropsychological deficits followed. With the advent of brain imaging, persistent or transient amnesia as the sole or primary manifestation of acute - mostly left-sided - hippocampal stroke was described. With the use of modern MRI techniques the identification of typical ischemic stroke lesion patterns affecting the hippocampus has become possible. Although overt cognitive deficits in unilateral hippocampal stroke seem to be rare, a careful neuropsychological examination might be necessary to detect resulting neuropsychological deficits including disturbances of verbal and nonverbal episodic long-term memory and spatial orientation.

  20. 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.

  1. 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

  2. SEIZURE AND EPILEPSY: STUDIES OF SEIZURE DISORDERS IN DROSOPHILA

    PubMed Central

    Parker, Louise; Howlett, Iris C.; Rusan, Zeid M.; Tanouye, Mark A.

    2012-01-01

    Despite the frequency of seizure disorders in the human population, the genetic and physiological basis for these defects has been difficult to resolve. Although many genetic contributions to seizure susceptibility have been identified, these involve disparate biological processes, many of which are not neural specific. The large number and heterogeneous nature of the genes involved makes it difficult to understand the complex factors underlying the etiology of seizure disorders. Examining the effect known genetic mutations have on seizure susceptibility is one approach that may prove fruitful. This approach may be helpful in both understanding how different physiological processes affect seizure susceptibility and identifying novel therapeutic treatments. We review here factors contributing to seizure susceptibility in Drosophila, a genetically tractable system that provides a model for human seizure disorders. Seizure-like neuronal activities and behaviors in the fruit fly are described, as well as a set of mutations that exhibit features resembling some human epilepsies and render the fly sensitive to seizures. Especially interesting are descriptions of a novel class of mutations that are second-site mutations that act as seizure suppressors. These mutations revert epilepsy phenotypes back to the wild-type range of seizure susceptibility. The genes responsible for seizure suppression are cloned with the goal of identifying targets for lead compounds that may be developed into new antiepileptic drugs. PMID:21906534

  3. 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…

  4. Neuronal desynchronization as a trigger for seizure generation.

    PubMed

    Li, Yue; Fleming, Ioana Nicolaescu; Colpan, Mustafa Efkan; Mogul, David J

    2008-02-01

    Experimental reports have appeared which challenge the dogma that epileptic seizures arise as a consequence of neuronal hypersynchronization. We sought to explore what mechanisms that desynchronize neuronal firing could induce epileptic seizures. A computer model of connections in a mammalian hippocampal slice preparation was constructed including two recently-reported distinct inhibitory feedback circuits. When inhibition by interneurons that synapse on pyramidal dendrites was decreased, highly localized seizure-like bursting was observed in the CA3 region similar to that which occurs experimentally under GABAergic blockade. In contrast, when inhibition by interneurons that synapse in the axosomatic region was similarly decreased, no such bursting was observed. However, when this transient inhibition was increased, normal coordinated spread of excitation was interrupted by high-frequency localized seizure-like bursting. The increase of this inhibitory input resulted in decreased cell coupling of pyramidal neurons. A decrease in phase coherence was initially observed until seizure-like activity initiated causing a net increase in coherence as has been observed in epileptic patients. These results provide a possible pathway in which a decrease in synchronization could provide the trigger for inducing epileptiform activity.

  5. Recurrent seizures and brain pathology after inhibition of glutamine synthetase in the hippocampus in rats.

    PubMed

    Eid, Tore; Ghosh, Arko; Wang, Yue; Beckström, Henning; Zaveri, Hitten P; Lee, Tih-Shih W; Lai, James C K; Malthankar-Phatak, Gauri H; de Lanerolle, Nihal C

    2008-08-01

    An excess of extracellular glutamate in the hippocampus has been linked to the generation of recurrent seizures and brain pathology in patients with medically intractable mesial temporal lobe epilepsy (MTLE). However, the mechanism which results in glutamate excess in MTLE remains unknown. We recently reported that the glutamate-metabolizing enzyme glutamine synthetase is deficient in the hippocampus in patients with MTLE, and we postulated that this deficiency is critically involved in the pathophysiology of the disease. To further explore the role of glutamine synthetase in MTLE we created a novel animal model of hippocampal glutamine synthetase deficiency by continuous (approximately 28 days) microinfusion of methionine sulfoximine (MSO: 0.625 to 2.5 microg/h) unilaterally into the hippocampus in rats. This treatment led to a deficiency in hippocampal glutamine synthetase activity by 82-97% versus saline. The majority (>95%) of the MSO-treated animals exhibited recurrent seizures that continued for several weeks. Some of the MSO-treated animals exhibited neuropathological features that were similar to mesial temporal sclerosis, such as hippocampal atrophy and patterned loss of hippocampal neurons. However, many MSO-treated animals displayed only minimal injury to the hippocampus, with no clear evidence of mesial temporal sclerosis. These findings support the hypothesis that a deficiency in hippocampal glutamine synthetase causes recurrent seizures, even in the absence of classical mesial temporal sclerosis, and that restoration of glutamine synthetase may represent a novel approach to therapeutic intervention in this disease.

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

    PubMed Central

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

    2015-01-01

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

  7. 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

  8. 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

  9. Epilepsy or seizures - discharge

    MedlinePlus

    ... food to the table. If possible, replace all glass doors either with safety glass or plastic. Most people with seizures can have a very active lifestyle. You should still plan ahead for the ... law from your doctor and the Department of Motor Vehicles (DMV).

  10. Antipsychotic drugs and seizures.

    PubMed

    Remick, R A; Fine, S H

    1979-02-01

    The authors examine the clinical problem of which antipsychotic drug to use when antipsychotics are indicated in patients with a seizuire disorder or who are susceptible to seizures. While definitive answers to this problem are still unknown, guidelines are offered for antipsychotic drug use in this situation, based on the author's understanding of psychotropics and epilepsy.

  11. Mutations in DEPDC5 cause familial focal epilepsy with variable foci.

    PubMed

    Dibbens, Leanne M; de Vries, Boukje; Donatello, Simona; Heron, Sarah E; Hodgson, Bree L; Chintawar, Satyan; Crompton, Douglas E; Hughes, James N; Bellows, Susannah T; Klein, Karl Martin; Callenbach, Petra M C; Corbett, Mark A; Gardner, Alison E; Kivity, Sara; Iona, Xenia; Regan, Brigid M; Weller, Claudia M; Crimmins, Denis; O'Brien, Terence J; Guerrero-López, Rosa; Mulley, John C; Dubeau, Francois; Licchetta, Laura; Bisulli, Francesca; Cossette, Patrick; Thomas, Paul Q; Gecz, Jozef; Serratosa, Jose; Brouwer, Oebele F; Andermann, Frederick; Andermann, Eva; van den Maagdenberg, Arn M J M; Pandolfo, Massimo; Berkovic, Samuel F; Scheffer, Ingrid E

    2013-05-01

    The majority of epilepsies are focal in origin, with seizures emanating from one brain region. Although focal epilepsies often arise from structural brain lesions, many affected individuals have normal brain imaging. The etiology is unknown in the majority of individuals, although genetic factors are increasingly recognized. Autosomal dominant familial focal epilepsy with variable foci (FFEVF) is notable because family members have seizures originating from different cortical regions. Using exome sequencing, we detected DEPDC5 mutations in two affected families. We subsequently identified mutations in five of six additional published large families with FFEVF. Study of families with focal epilepsy that were too small for conventional clinical diagnosis with FFEVF identified DEPDC5 mutations in approximately 12% of families (10/82). This high frequency establishes DEPDC5 mutations as a common cause of familial focal epilepsies. Shared homology with G protein signaling molecules and localization in human neurons suggest a role of DEPDC5 in neuronal signal transduction.

  12. Efficacy of lacosamide on seizures and myoclonus in a patient with epilepsia partialis continua.

    PubMed

    Spalletti, Maddalena; Comanducci, Angela; Vagaggini, Alessandro; Bucciardini, Luca; Grippo, Antonello; Amantini, Aldo

    2013-06-01

    A 39-year-old male with epilepsia partialis continua, refractory to first- and second-line antiepileptic drugs, is described. Lacosamide produced a progressive antiepileptic effect on Jacksonian motor seizures and subsequently on positive myoclonus, which developed into negative myoclonus before complete resolution. Our report confirms the efficacy of lacosamide on focal motor refractory status epilepticus and documents a unique effect of lacosamide on seizure semiology.

  13. Ischemia-induced degeneration of CA1 pyramidal cells decreases seizure severity in a subgroup of epileptic gerbils and affects parvalbumin immunoreactivity of CA1 interneurons.

    PubMed

    Winkler, D T; Scotti, A L; Nitsch, C

    2001-04-01

    Mongolian gerbils are epilepsy-prone animals. In adult gerbils two major groups can be differentiated according to their seizure behavior: Highly seizure-sensitive gerbils exhibit facial and forelimb clonus or generalized tonic-clonic seizures from the first test on, while kindled-like gerbils are seizure free for the first three to six consecutive tests, later develop forelimb myoclonus, and eventually progress to generalized tonic-clonic seizures. In the hippocampus, seizure history of the individual animal is mirrored in the intensity in which GABAergic neurons are immunostained for the calcium-binding protein parvalbumin: they lose parvalbumin with increasing seizure incidence. In a first step to clarify the influence of hippocampal projection neurons on spontaneous seizure behavior and related parvalbumin expression, we induced degeneration of the CA1 pyramidal cells by transient forebrain ischemia. This results in a decreased seizure sensitivity in highly seizure-sensitive gerbils. The kindling-like process, however, is not permanently blocked by the ischemic nerve cell loss, suggesting that an intact CA1 field is not a prerequisite for the development of seizure behavior. The seizure-induced loss of parvalbumin from the ischemia-resistant interneurons recovers after ischemia. Thus, changes in parvalbumin content brought about by repeated seizures are not permanent but can rather be modulated by novel stimuli.

  14. Ictal EEG/fMRI study of vertiginous seizures.

    PubMed

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

    2017-03-01

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

  15. Prenatal protein malnutrition and hippocampal function: rapid kindling.

    PubMed

    Austin-Lafrance, R J; Morgane, P J; Bronzino, J D

    1991-12-01

    A stimulation paradigm evoking rapidly recurring seizure activity from the hippocampal dentate gyrus was used to examine perforant path kindling in prenatally protein malnourished adult rats. Biphasic electrical stimulations (50 Hz) of five s duration were applied to the perforant path every five min for one hour over five consecutive days. Behavioral manifestations of seizure activity were assessed using the standard 0-5 scale. Prenatally malnourished rats exhibited significantly fewer convulsive seizures (stage 5) and required significantly more stimulations to attain the first stage 5 seizure than controls. Animals of the malnourished group also exhibited significantly more stage 1 seizures than control animals, indicating a significant retardation in the kindling rate of these animals. Additionally, 3 of the 11 malnourished animals failed to exhibit a single stage 5 seizure during the 60 stimulation test period. These findings parallel previous results reported for prenatally protein malnourished rats using the traditional one stimulation-per-day kindling paradigm and indicate that this rapid kindling paradigm can be effectively used to study the impact of various insults on seizure susceptibility and development in a shortened time frame.

  16. Knife cuts of entorhinal cortex: effects on development of amygdaloid kindling and seizure-induced decrease of muscarinic cholinergic receptors

    SciTech Connect

    Savage, D.D.; Rigsbee, L.C.; McNamara, J.O.

    1985-02-01

    This report examines the effect of transection of the entorhinal hippocampal projection on amygdaloid kindling. We found that: bilateral knife cuts of entorhinal cortex but not of dorsal neocortex antagonize the development of amygdaloid kindling; and bilateral knife cuts of entorhinal cortex eliminate the seizure-induced decrease in number of muscarinic receptors of dentate granule cells. We suggest the following interpretations of these data: the hippocampal formation circuitry facilitates the development of amygdaloid kindling; and the decline of muscarinic receptors after kindled seizures is due to excessive activation of granule cells by axons from entorhinal cortex, a noncholinergic afferent.

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

    PubMed Central

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

    2013-01-01

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

  18. 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.

  19. Gelastic seizures: incidence, clinical and EEG features in adult patients undergoing video-EEG telemetry.

    PubMed

    Kovac, Stjepana; Diehl, Beate; Wehner, Tim; Fois, Chiara; Toms, Nathan; Walker, Matthew C; Duncan, John S

    2015-01-01

    This study aimed to determine clinical features of adult patients with gelastic seizures recorded on video -electroencephalography (EEG) over a 5-year period. We screened video-EEG telemetry reports for the occurrence of the term "gelastic" seizures, and assessed the semiology, EEG features, and duration of those seizures. Gelastic seizures were identified in 19 (0.8%) of 2,446 admissions. The presumed epileptogenic zone was in the hypothalamus in one third of the cases, temporal lobe epilepsy was diagnosed in another third, and the remainder of the cases presenting with gelastic seizures were classified as frontal, parietal lobe epilepsy or remained undetermined or were multifocal. Gelastic seizures were embedded in a semiology, with part of the seizure showing features of automotor seizures. A small proportion of patients underwent epilepsy surgery. Outcome of epilepsy surgery was related to the underlying pathology; two patients with hippocampal sclerosis had good outcomes following temporal lobe resection and one of four patients with hypothalamic hamartomas undergoing gamma knife surgery had a good outcome.

  20. Mechanism of Highly Synchronized Bilateral Hippocampal Activity

    PubMed Central

    Wang, Y.; Toprani, S.; Tang, Y.; Vrabec, T.; Durand, D.M.

    2014-01-01

    In vivo studies of epileptiform discharges in the hippocampi of rodents have shown that bilateral seizure activity can sometimes be synchronized with very small delays (< 2 ms). This observed small time delay of epileptiform activity between the left and right CA3 regions is unexpected given the physiological propagation time across the hemispheres (> 6 ms). The goal of this study is to determine the mechanisms of this tight synchronization with in-vitro electrophysiology techniques and computer simulations. The hypothesis of a common source was first eliminated by using an in-vitro preparation containing both hippocampi with a functional ventral hippocampal commissure (VHC) and no other tissue. Next, the hypothesis that a noisy baseline could mask the underlying synchronous activity between the two hemispheres was ruled out by low noise in-vivo recordings and computer simulation of the noisy environment. Then we built a novel bilateral CA3 model to test the hypothesis that the phenomenon of very small left-to-right propagation delay of seizure activity is a product of epileptic cell network dynamics. We found that the commissural tract connectivity could decrease the delay between seizure events recorded from two sides while the activity propagated longitudinally along the CA3 layer thereby yielding delays much smaller than the propagation time between the two sides. The modeling results indicate that both recurrent and feedforward inhibition were required for shortening the bilateral propagation delay and depended critically on the length of the commissural fiber tract as well as the number of cells involved in seizure generation. These combined modeling/experimental studies indicate that it is possible to explain near perfect synchronization between the two hemispheres by taking into account the structure of the hippocampal network. PMID:24262205

  1. Gelastic seizures due to hypothalamic hamartoma: rapid resolution after endoscopic tumor disconnection.

    PubMed

    Incorpora, Gemma; Pavone, Piero; Castellano-Chiodo, Danilo; Praticò, Andrea Domenico; Ruggieri, Martino; Pavone, Lorenzo

    2013-01-01

    Gelastic epilepsy are focal seizures manifesting as recurrent brief seizures starting as laughter or grimaces. They are most commonly associated with other types of seizures and can be secondary to infectious, malformative, metabolic, or neoplastic processes involving the central nervous system. We report on an 18-month-old girl who presented since the age of 2 months with multiple, recurrent, unprovoked episodes of stereotypical laughter. Brain magnetic resonance study revealed an hypothalamic hamartoma. Endoscopic tumor disconnection of the hamartoma resulted in rapid resolution of neurological symptomatology.

  2. [Anticonvulsive Therapy after the First Unprovoked Seizure – Pros and Cons].

    PubMed

    Zieglgänsberger, Dominik; Tettenborn, Barbara

    2016-01-06

    A first seizure is a critical life time event with severe consequences. A very thorough work-up is needed to find out the cause of the seizure and to number the risk of recurrence. Reasons for an anticonvulsive therapy are a pathologic EEG, a pathologic neurologic examination, the proof of a structural lesion, focal seizure onset or seizure onset while sleeping or classification as an epilepsy syndrome with high recurrence risk like juvenile myoclonic epilepsy or juvenile absence epilepsy. Psychological and social aspects like the patients or relatives fear of a further seizure, the risk of injury and occupational and recreational aspects must be considered as well. Reasons against an anticonvulsive therapy are mainly related to adverse effects like gain of weight and osteoporosis.

  3. Termination of epileptiform activity by cooling in rat hippocampal slice epilepsy models.

    PubMed

    Motamedi, Gholam K; Salazar, Patricia; Smith, Eric L; Lesser, Ronald P; Webber, William R S; Ortinski, Pavel I; Vicini, Stefano; Rogawski, Michael A

    2006-08-01

    Cooling has been shown to terminate experimentally induced epileptiform activity in models of epilepsy without causing injury to the cooled brain, suggesting that cooling could represent an approach to seizure control in intractable focal epilepsies. Here we sought to determine the most effective way to apply cooling to abort spontaneous epileptiform discharges in in vitro brain slice models. We induced spontaneous epileptiform activity in rat brain slices by exposure to 4-aminopyridine (4-AP), 4-AP plus bicuculline, and Mg(2+)-free artificial CSF (aCSF) at 28-34 degrees C. Extracellular field recordings were made at hippocampal or neocortical sites. Slice temperature was reduced by perfusion with cold aCSF. Rapid cooling at rates of 2-5 degrees C/s was compared to cooling at slower rates of 0.1-1 degrees C/s. Cooling at both rates reversibly aborted epileptiform discharges in all three models and at all recording sites. With rapid cooling, small temperature drops were highly effective in terminating discharges, an effect that was sustained for as long as the reduced temperature level was maintained. In contrast, slow cooling required much larger temperature drops to inhibit discharges. With slow cooling, absolute temperature drops to 21-22 degrees C caused a 90% reduction in event frequency, but cooling to 14-15 degrees C was required to terminate discharges. We conclude that rapid cooling as effectively aborts discharges in in vitro epilepsy models as does slow cooling, but the magnitude of the temperature change required is less. Practical devices to inhibit seizure activity may only need to induce small temperature drops, if the cooling can be applied sufficiently rapidly.

  4. Detection of seizure precursors from depth-EEG using a sign periodogram transform.

    PubMed

    Niederhauser, Joël J; Esteller, Rosana; Echauz, Javier; Vachtsevanos, George; Litt, Brian

    2003-04-01

    Brief bursts of focal, low amplitude rhythmic activity have been observed on depth electroencephalogram (EEG) in the minutes before electrographic onset of seizures in human mesial temporal lobe epilepsy. We have found these periods to contain discrete, individualized synchronized activity in patient-specific frequency bands ranging from 20 to 40 Hz. We present a method for detecting and displaying these events using a periodogram of the sign-limited temporal derivative of the EEG signal, denoted joint sign periodogram event characterization transform (JSPECT). When applied to continuous 2-6 day depth-EEG recordings from ten patients with temporal lobe epilepsy, JSPECT demonstrated that these patient-specific EEG events reliably occurred 5-80 s prior to electrical onset of seizures in five patients with focal, unilateral seizure onsets. JSPECT did not reveal this type of activity prior to seizures in five other patients with bilateral, extratemporal or more diffuse seizure onsets on EEG. Patient-specific, localized rhythmic events may play an important role in seizure generation in temporal lobe epilepsy. The JSPECT method efficiently detects these events, and may be useful as part of an automated system for predicting electrical seizure onset in appropriate patients.

  5. 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

  6. Network dynamics of the brain and influence of the epileptic seizure onset zone.

    PubMed

    Burns, Samuel P; Santaniello, Sabato; Yaffe, Robert B; Jouny, Christophe C; Crone, Nathan E; Bergey, Gregory K; Anderson, William S; Sarma, Sridevi V

    2014-12-09

    The human brain is a dynamic networked system. Patients with partial epileptic seizures have focal regions that periodically diverge from normal brain network dynamics during seizures. We studied the evolution of brain connectivity before, during, and after seizures with graph-theoretic techniques on continuous electrocorticographic (ECoG) recordings (5.4 ± 1.7 d per patient, mean ± SD) from 12 patients with temporal, occipital, or frontal lobe partial onset seizures. Each electrode was considered a node in a graph, and edges between pairs of nodes were weighted by their coherence within a frequency band. The leading eigenvector of the connectivity matrix, which captures network structure, was tracked over time and clustered to uncover a finite set of brain network states. Across patients, we found that (i) the network connectivity is structured and defines a finite set of brain states, (ii) seizures are characterized by a consistent sequence of states, (iii) a subset of nodes is isolated from the network at seizure onset and becomes more connected with the network toward seizure termination, and (iv) the isolated nodes may identify the seizure onset zone with high specificity and sensitivity. To localize a seizure, clinicians visually inspect seizures recorded from multiple intracranial electrode contacts, a time-consuming process that may not always result in definitive localization. We show that network metrics computed from all ECoG channels capture the dynamics of the seizure onset zone as it diverges from normal overall network structure. This suggests that a state space model can be used to help localize the seizure onset zone in ECoG recordings.

  7. 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

  8. Cerebrospinal fluid findings in children with fever-associated status epilepticus: results of the consequences of prolonged febrile seizures (FEBSTAT) study.

    PubMed

    Frank, L Matthew; Shinnar, Shlomo; Hesdorffer, Dale C; Shinnar, Ruth C; Pellock, John M; Gallentine, William; Nordli, Douglas R; Epstein, Leon G; Moshé, Solomon L; Lewis, Darrell V; Sun, Shumei

    2012-12-01

    This prospective multicenter study of 200 patients with fever-associated status epilepticus (FSE), of whom 136 underwent a nontraumatic lumbar puncture, confirms that FSE rarely causes cerebrospinal fluid (CSF) pleocytosis. CSF glucose and protein levels were unremarkable. Temperature, age, seizure focality, and seizure duration did not affect results. CSF pleocytosis should not be attributed to FSE.

  9. Neuroligin-1 Knockdown Suppresses Seizure Activity by Regulating Neuronal Hyperexcitability.

    PubMed

    Fang, Min; Wei, Jin-Lai; Tang, Bo; Liu, Jing; Chen, Ling; Tang, Zhao-Hua; Luo, Jing; Chen, Guo-Jun; Wang, Xue-Feng

    2016-01-01

    Abnormally synchronized synaptic transmission in the brain leads to epilepsy. Neuroligin-1 (NL1) is a synaptic cell adhesion molecule localized at excitatory synapses. NL1 modulates synaptic transmission and determines the properties of neuronal networks in the mammalian central nervous system. We showed that the expression of NL1 and its binding partner neurexin-1β was increased in temporal lobe epileptic foci in patients and lithium-pilocarpine-treated epileptic rats. We investigated electrophysiological and behavioral changes in epileptic rats after lentivirally mediated NL1 knockdown in the hippocampus to determine whether NL1 suppression prevented seizures and, if so, to explore the probable underlying mechanisms. Our behavioral studies revealed that NL1 knockdown in epileptic rats reduced seizure severity and increased seizure latency. Whole-cell patch-clamp recordings of CA1 pyramidal neurons in hippocampal slices from NL1 knockdown epileptic rats revealed a decrease in spontaneous action potential frequency and a decrease in miniature excitatory postsynaptic current (mEPSC) frequency but not amplitude. The amplitude of N-methyl-D-aspartate receptor (NMDAR)-dependent EPSCs was also selectively decreased. Notably, NL1 knockdown reduced total NMDAR1 expression and the surface/total ratio in the hippocampus of epileptic rats. Taken together, these data indicate that NL1 knockdown in epileptic rats may reduce the frequency and severity of seizures and suppress neuronal hyperexcitability via changes in postsynaptic NMDARs.

  10. Severe depression as the sole symptom of affective focal status epilepticus

    PubMed Central

    Dimitriadis, Konstantinos; Pfefferkorn, Thomas; Noachtar, Soheyl

    2014-01-01

    Depression as well as fear, joy and anger have been described as the semiological features of focal epileptic seizures. When emotions present as the sole symptoms of epileptic seizures, they may easily be misdiagnosed as a psychiatric disorder. We describe a patient with affective focal status epilepticus, secondary to limbic encephalitis, in which depression was the only clinical manifestation. Through EEG correlates the epileptic nature of depression could be proven. Furthermore, we discuss the association between epilepsy and depression, as well as the link between ictal depression and suicidal rates. PMID:24827645

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

    PubMed Central

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

    2015-01-01

    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 Scn8amed and Scn8amed-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

  12. "Tectonic" hippocampal malformations in patients with temporal lobe epilepsy.

    PubMed

    Sloviter, Robert S; Kudrimoti, Hemant S; Laxer, Kenneth D; Barbaro, Nicholas M; Chan, Stephen; Hirsch, Lawrence J; Goodman, Robert R; Pedley, Timothy A

    2004-01-01

    Histological analysis of hippocampi removed en bloc during surgical treatment of temporal lobe epilepsy revealed a subgroup of patients with bulbous expansions of the CA1 pyramidal cell/subicular layers that were consistently accompanied by "tectonic" invaginations of the adjacent dentate gyrus. Most hippocampi containing the CA1/subicular anomaly and the tectonically deformed dentate gyrus exhibited minor cell loss compared to hippocampi with typical hippocampal sclerosis, and retrospective analysis revealed that conventional imaging methods usually failed to detect subtle hippocampal atrophy or abnormal signal characteristics in patients with this anomaly. Cells within the anomaly exhibited the spherical appearance of undifferentiated pyramidal layer neurons, and were immunopositive for the neuronal marker NeuN. Immunostaining for the synaptic marker beta-synuclein suggested abnormal dentate gyrus lamination in segments containing the pyramidal cell layer anomaly, but not in unaffected areas of the same specimens. Despite differences in the extent of neuronal loss between patients with hippocampal sclerosis and those with the CA1/subicular anomaly, the incidence of antecedent febrile seizures was similar in both groups. In a comparison group of hippocampi obtained at autopsy, structural irregularities were evident, but were consistently less disruptive to hippocampal architecture than the anomalies observed in epilepsy patients. We hypothesize that developmental malformation of the CA1 pyramidal cell/subicular layers may adversely influence the subsequent development of the adjacent dentate gyrus, and may render temporal lobe structures hyperexcitable and more vulnerable to relatively innocuous seizures and injuries. Thus, these presumably developmental hippocampal anomalies may serve as substrates for early febrile seizures and subsequent epilepsy.

  13. Medial temporal lobe heterotopia as a cause of increased hippocampal and amygdaloid MRI volumes.

    PubMed

    Watson, C; Nielsen, S L; Cobb, C; Burgerman, R; Williamson, B

    1996-10-01

    Magnetic resonance imaging (MRI)-based volumetric measurements of the hippocampus and amygdala are useful in detecting hippocampal and amygdaloid sclerosis in patients with temporal lobe epilepsy. In these pathological entities, volumetric MRI analysis shows the epileptogenic structures to be atrophic when compared to the normal, nonepileptogenic side. Described are 2 patients with increased hippocampal and amygdaloid volumes on the side of seizure onset due to medial temporal lobe heteroto pias. Care must be taken in the interpretation of volumetric MRI data to make certain that asymmetries in hippocampal and amygdaloid measurements are due to atrophy and sclerosis of the abnormal side and not to increased tissue such as heterotopic gray matter.

  14. 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…

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

    PubMed

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

    2015-09-01

    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.

  16. Multistage seizure detection techniques optimized for low-power hardware platforms.

    PubMed

    Raghunathan, Shriram; Jaitli, Arjun; Irazoqui, Pedro P

    2011-12-01

    Closed-loop neurostimulation devices that stimulate the brain to treat epileptic seizures have shown great promise in treating more than a third of the 2 million people with epilepsy in the United States alone whose seizures are currently nonresponsive to pharmaceutical treatment. Seizure detection algorithms facilitate responsive therapeutic intervention that is believed to increase the efficacy of neurostimulation by improving on its spatial and temporal specificity. Translating these signal processing algorithms into battery-powered, implantable devices poses a number of challenges that severely limit the computational power of the chosen algorithm. We propose a cascaded two-stage seizure detection algorithm that is computationally efficient (resulting in a low-power hardware implementation) without compromising on detection efficacy. Unlike traditional detection algorithms, the proposed technique does not explicitly require a "training" phase from individual to individual and, instead, relies on using features that result in distinct "patterns" at the electrographic seizure onset. We tested the algorithm on spontaneous clinical seizures recorded using depth electrodes from patients with focal intractable epilepsy and annotated by epileptologists at the University of Freiburg Medical Center, via the Freiburg database. The algorithm performs with a specificity and sensitivity of 99.82 and 87.5%, detecting seizures in less than 9.08% of their duration after onset. The proposed technique is also shown to be computationally efficient, facilitating low-power hardware implementation. This article is part of a Supplemental Special Issue entitled The Future of Automated Seizure Detection and Prediction.

  17. Silencing microRNA-134 produces neuroprotective and prolonged seizure-suppressive effects

    PubMed Central

    Jimenez-Mateos, Eva M.; Engel, Tobias; Merino-Serrais, Paula; McKiernan, Ross C.; Tanaka, Katsuhiro; Mouri, Genshin; Sano, Takanori; O’Tuathaigh, Colm; Waddington, John L.; Prenter, Suzanne; Delanty, Norman; Farrell, Michael A.; O’Brien, Donncha F.; Conroy, Ronán M.; Stallings, Raymond L.; deFelipe, Javier; Henshall, David C.

    2012-01-01

    Temporal lobe epilepsy is a common, chronic neurologic disorder characterized by recurrent spontaneous seizures. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate post-transcriptional expression of protein-coding mRNAs, which may have important roles in the pathogenesis of neurologic disorders. In models of prolonged, injurious seizures (status epilepticus) and in experimental and human epilepsy, we found up-regulation of miR-134, a brain-specific, activity-regulated miRNA implicated in the control of dendritic spine morphology. Silencing of miR-134 expression in vivo using antagomirs reduced hippocampal CA3 pyramidal neuron dendrite spine density by 21%, and rendered mice refractory to seizures and hippocampal injury caused by status epilepticus. Depletion of miR-134 after status epilepticus reduced the later occurrence of spontaneous seizures by over 90% and mitigated attendant pathologic features of temporal lobe epilepsy. Thus, silencing miR-134 exerts prolonged seizure suppressant and neuroprotective actions; whether these represent anticonvulsant or truly antiepileptogenic effects requires additional experimentation. PMID:22683779

  18. Inverse relationship between seizure expression and extrasynaptic NMDAR function following chronic NMDAR inhibition.

    PubMed

    Bausch, Suzanne B; He, Shuijin; Dong, Yu

    2010-07-01

    We showed previously that electrographic seizures involving dentate granule cells in organotypic hippocampal slice cultures were dramatically reduced following chronic treatment with the NR2B-selective antagonist, Ro25,6981, but were increased following chronic treatment with the high-affinity competitive antagonist, D(-)-2-amino-5-phosphonopentanoic acid (D-APV). To begin to investigate the potential mechanisms underlying the differential effects of N-methyl-D-aspartate receptor (NMDAR) antagonists on seizures, electrophysiologic experiments were conducted in dentate granule cells in hippocampal slice cultures treated for the entire 17-21 day culture period with vehicle, Ro25,6981 or D-APV. Initial experiments revealed a lack of an association between miniature excitatory postsynaptic current (mEPSC) measures and seizures suggesting that shifts in mEPSC were unlikely to account for the differential effects of D-APV and Ro25,6981 on seizures. However, the amplitude of tonic NMDAR-mediated currents was reduced in cultures treated chronically with D-APV and dramatically enhanced in cultures treated chronically with Ro25,6981. Because tonic NMDAR currents are mediated primarily by extrasynaptic NMDAR, these data show an inverse relationship between changes in extrasynaptic NMDAR function and alterations in seizure expression.

  19. 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.

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

    PubMed

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

    2014-01-01

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

  1. Febrile seizures - what to ask your doctor

    MedlinePlus

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

  2. 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

  3. Kainate, a double agent that generates seizures: two decades of progress.

    PubMed

    Ben-Ari, Y; Cossart, R

    2000-11-01

    Studies using kainate, an excitatory amino acid extracted from a seaweed, have provided major contributions to the understanding of epileptogenesis. Here we review pioneering and more recent studies aimed at determining how kainate generates seizures and, in particular, how inhibition is altered during seizures. We focus on target and subunit-specific effects of kainate on hippocampal pyramidal neurons and interneurons that lead to an excitation of both types of neurons and thus to the parallel increase of glutamatergic and GABAergic spontaneous currents. We propose that kainate excites all its targets, the net consequence depending on the level of activity of the network.

  4. Mutations in KCNT1 cause a spectrum of focal epilepsies.

    PubMed

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

    2015-09-01

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

  5. Effects of selective neonatal hippocampal lesions on tests of object and spatial recognition memory in monkeys.

    PubMed

    Heuer, Eric; Bachevalier, Jocelyne

    2011-04-01

    Earlier studies in monkeys have reported mild impairment in recognition memory after nonselective neonatal hippocampal lesions. To assess whether the memory impairment could have resulted from damage to cortical areas adjacent to the hippocampus, we tested adult monkeys with neonatal focal hippocampal lesions and sham-operated controls in three recognition tasks: delayed nonmatching-to-sample, object memory span, and spatial memory span. Further, to rule out that normal performance on these tasks may relate to functional sparing following neonatal hippocampal lesions, we tested adult monkeys that had received the same focal hippocampal lesions in adulthood and their controls in the same three memory tasks. Both early and late onset focal hippocampal damage did not alter performance on any of the three tasks, suggesting that damage to cortical areas adjacent to the hippocampus was likely responsible for the recognition impairment reported by the earlier studies. In addition, given that animals with early and late onset hippocampal lesions showed object and spatial recognition impairment when tested in a visual paired comparison task, the data suggest that not all object and spatial recognition tasks are solved by hippocampal-dependent memory processes. The current data may not only help explain the neural substrate for the partial recognition memory impairment reported in cases of developmental amnesia, but they are also clinically relevant given that the object and spatial memory tasks used in monkeys are often translated to investigate memory functions in several populations of human infants and children in which dysfunction of the hippocampus is suspected.

  6. [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.

  7. 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…

  8. 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

  9. 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

  10. 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

  11. Rapid and accurate assessment of seizure liability of drugs by using an optimal support vector machine method.

    PubMed

    Zhang, Hui; Li, Wei; Xie, Yang; Wang, Wen-Jing; Li, Lin-Li; Yang, Sheng-Yong

    2011-12-01

    Drug-induced seizures are a serious adverse effect and assessment of seizure risk usually takes place at the late stage of drug discovery process, which does not allow sufficient time to reduce the risk by chemical modification. Thus early identification of chemicals with seizure liability using rapid and cheaper approaches would be preferable. In this study, an optimal support vector machine (SVM) modeling method has been employed to develop a prediction model of seizure liability of chemicals. A set of 680 compounds were used to train the SVM model. The established SVM model was then validated by an independent test set comprising 175 compounds, which gave a prediction accuracy of 86.9%. Further, the SVM-based prediction model of seizure liability was compared with various preclinical seizure assays, including in vitro rat hippocampal brain slice, in vivo zebrafish larvae assay, mouse spontaneous seizure model, and mouse EEG model. In terms of predictability, the SVM model was ranked just behind the mouse EEG model, but better than the rat brain slice and zebrafish models. Nevertheless, the SVM model has considerable advantages compared with the preclinical seizure assays in speed and cost. In summary, the SVM-based prediction model of seizure liability established here offers potential as a cheaper, rapid and accurate assessment of seizure liability of drugs, which could be used in the seizure risk assessment at the early stage of drug discovery. The prediction model is freely available online at http://www.sklb.scu.edu.cn/lab/yangsy/download/ADMET/seizure_pred.tar.

  12. The alpha2 adrenoreceptor agonist clonidine suppresses evoked and spontaneous seizures, whereas the alpha2 adrenoreceptor antagonist idazoxan promotes seizures in amygdala-kindled kittens.

    PubMed

    Shouse, Margaret N; Scordato, John C; Farber, Paul R; de Lanerolle, Nihal

    2007-03-16

    Microinfusion of alpha2 adrenoreceptor agonists and antagonists into amygdala has contrasting effects on evoked and spontaneous seizure susceptibility in amygdala-kindled kittens. Subjects were 14 preadolescent kittens between 3 and 4 months old at the beginning of kindling. The same protocol was followed except that half the kittens received microinfusions (1 mul) of the alpha2 agonist clonidine (CLON; 1.32 nmol), and half received the alpha2 antagonist idazoxan (IDA; 0.33 nmol). Infusions were made over 1 min through needles inserted into cannulae adjacent to stimulating electrodes in the kindled amygdala, and evoked seizures were tested 10-12 min later. The results were: (1) CLON elevated seizure thresholds obtained once at the beginning and end of kindling, but only when compared to sham control values (needle insertion only) in the same animals; IDA significantly reduced thresholds. (2) CLON retarded and IDA accelerated kindling rate, defined as the number of afterdischarges (ADs) required to achieve the first stage 6 seizure or generalized tonic-clonic convulsion (GTC). These effects were most pronounced on the emergence of seizure "generalization" stages (3-6) from "focal" seizure stages (1-2). (3) CLON prevented onset of spontaneous seizures, whereas IDA precipitated onset of spontaneous seizures in 100% of the animals before or during the 5-week post-kindling follow-up during which seizures were evoked once each work day. The study confirms previous findings in kindled rodents to show that CLON and IDA can have opposing effects on kindling development in kittens and is the first report to show contrasting effects on spontaneous epileptogenesis in kindled animals as well.

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

    PubMed

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

    2017-01-01

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

  14. [Focal epithelial hyperplasia].

    PubMed

    Vera-Iglesias, E; García-Arpa, M; Sánchez-Caminero, P; Romero-Aguilera, G; Cortina de la Calle, P

    2007-11-01

    Focal epithelial hyperplasia is a rare disease of the oral mucosa caused by the human papilloma virus (HPV). It appears as a benign epithelial growth, usually in the mucosa of the lower lip. It is mainly associated with HPV serotypes 13 and 32 and there is a clear racial predilection for the disease in Native Americans and Eskimos. We describe the case of a 17-year-old girl from Ecuador with multiple papular lesions in both lips that were clinically and histologically consistent with focal epithelial hyperplasia. Analysis by polymerase chain reaction detected HPV serotype 13.

  15. Vitelliform focal choroidal excavation.

    PubMed

    Or, Chris; Forooghian, Farzin

    2014-05-30

    Focal choroidal excavations (FCE) are characterized by foveal or perifoveal choroid excavations seen on optical coherence tomography (OCT). The authors report a case of FCE associated with a vitelliform lesion within the excavation. A case of FCE associated with a small vitelliform lesion has been described previously, but the larger extent of the vitelliform lesion observed in the current case has not been previously reported. This may represent a novel category of FCE, vitelliform focal choroidal excavation, in which deposition of vitelliform material is associated with its development.

  16. SNAP focal plane

    SciTech Connect

    Lampton, Michael L.; Kim, A.; Akerlof, C.W.; Aldering, G.; Amanullah, R.; Astier, P.; Barrelet, E.; Bebek, C.; Bergstrom, L.; Berkovitz, J.; Bernstein, G.; Bester, M.; Bonissent, A.; Bower, C.; Carithers Jr., W.C.; Commins, E.D.; Day, C.; Deustua, S.E.; DiGennaro,R.; Ealet, A.; Ellis, R.S.; Eriksson, M.; Fruchter, A.; Genat, J.-F.; Goldhaber, G.; Goobar, A.; Groom, D.; Harris, S.E.; Harvey, P.R.; Heetderks, H.D.; Holland, S.E.; Huterer, D.; Karcher, A.; Kolbe, W.; Krieger, B.; Lafever, R.; Lamoureux, J.; Levi, M.E.; Levin, D.S.; Linder,E.V.; Loken, S.C.; Malina, R.; Massey, R.; McKay, T.; McKee, S.P.; Miquel, R.; Mortsell, E.; Mostek, N.; Mufson, S.; Musser, J.; Nugent, P.; Oluseyi, H.; Pain, R.; Palaio, N.; Pankow, D.; Perlmutter, S.; Pratt, R.; Prieto, E.; Refregier, A.; Rhodes, J.; Robinson, K.; Roe, N.; Sholl, M.; Schubnell, M.; Smadja, G.; Smoot, G.; Spadafora, A.; Tarle, G.; Tomasch,A.; von der Lippe, H.; Vincent, R.; Walder, J.-P.; Wang, G.

    2002-07-29

    The proposed SuperNova/Acceleration Probe (SNAP) mission will have a two-meter class telescope delivering diffraction-limited images to an instrumented 0.7 square-degree field sensitive in the visible and near-infrared wavelength regime. We describe the requirements for the instrument suite and the evolution of the focal plane design to the present concept in which all the instrumentation--visible and near-infrared imagers, spectrograph, and star guiders--share one common focal plane.

  17. 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

  18. EFFECT OF AGE ON KAINATE-INDUCED SEIZURE SEVERITY AND CELL DEATH

    PubMed Central

    McCord, Meghan C.; Lorenzana, Ariana; Bloom, Christopher S.; Chancer, Zackary O.; Schauwecker, P. Elyse

    2008-01-01

    While the onset and extent of epilepsy increases in the aged population, the reasons for this increased incidence remain unexplored. The present study used two inbred strains of mice (C57BL/6J and FVB/NJ) to address the genetic control of age-dependent neurodegeneration by building upon previous experiments that have identified phenotypic differences in susceptibility to hippocampal seizure-induced cell death. We determined if seizure induction and seizure-induced cell death are affected differentially in young adult, mature, and aged male C57BL/6J and FVB/NJ mice administered the excitotoxin, kainic acid. Dose response testing was performed in three-four groups of male mice from each strain. Following kainate injections, mice were scored for seizure activity and brains from mice in each age group were processed for light microscopic histopathologic evaluation seven days following kainate administration to evaluate the severity of seizure-induced brain damage. Irrespective of the dose of kainate administered or the age group examined, resistant strains of mice (C57BL/6J) continued to be resistant to seizure-induced cell death. In contrast, aged animals of the FVB/NJ strain were more vulnerable to the induction of behavioral seizures and associated neuropathology after systemic injection of kainic acid than young or middle-aged mice. Results from these studies suggest that the age-related increased susceptibility to the neurotoxic effects of seizure induction and seizure-induced injury is regulated in a strain-dependent manner, similar to previous observations in young adult mice. PMID:18479826

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  1. 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

  2. Interictal and Postictal Performances on Dichotic Listening Test in Children with Focal Epilepsy

    ERIC Educational Resources Information Center

    Carlsson, G.; Wiegand, G.; Stephani, U.

    2011-01-01

    Dichotic listening test (DL) is an important tool to disclose speech dominance in healthy subjects and in clinical cases. The aim of this study was to probe if focal epilepsy in children reveals a corresponding suppression of the ear reports contralateral to seizure onset site. Thus, 15 children and adolescents with clinically and…

  3. Low and High Frequency Hippocampal Stimulation for Drug‐Resistant Mesial Temporal Lobe Epilepsy

    PubMed Central

    Lim, Siew‐Na; Lee, Ching‐Yi; Lee, Shih‐Tseng; Tu, Po‐Hsun; Chang, Bao‐Luen; Lee, Chih‐Hong; Cheng, Mei‐Yun; Chang, Chun‐Wei; Tseng, Wei‐En Johnny; Hsieh, Hsiang‐Yao; Chiang, Hsing‐I

    2016-01-01

    Objective Electrical stimulation of the hippocampus offers the possibility to treat patients with mesial temporal lobe epilepsy (MTLE) who are not surgical candidates. We report long‐term follow‐up results in five patients receiving low or high frequency hippocampal stimulation for drug‐resistant MTLE. Materials and Methods The patients underwent stereotactic implantation of quadripolar stimulating electrodes in the hippocampus. Two of the patients received unilateral electrode implantation, while the other three received bilateral implantation. Stimulation of the hippocampal electrodes was turned ON immediately after the implantation of an implantable pulse generator, with initial stimulation parameters: 1 V, 90–150 μs, 5 or 145 Hz. The frequency of seizures was monitored and compared with preimplantation baseline data. Results Two men and three women, aged 27–61 years were studied, with a mean follow‐up period of 38.4 months (range, 30–42 months). The baseline seizure frequency was 2.0–15.3/month. The five patients had an average 45% (range 22–72%) reduction in the frequency of seizures after hippocampal stimulation over the study period. Low frequency hippocampal stimulation decreased the frequency of seizures in two patients (by 54% and 72%, respectively). No implantation‐ or stimulation‐related side effects were reported. Conclusions Electrical stimulation of the hippocampus is a minimally invasive and reversible method that can improve seizure outcomes in patients with drug‐resistant MTLE. The optimal frequency of stimulation varied from patient to patient and therefore required individual setting. These experimental results warrant further controlled studies with a large patient population to evaluate the long‐term effect of hippocampal stimulation with different stimulation parameters. PMID:27072376

  4. Seizures and Epileptiform Patterns in SAH and Their Relation to Outcomes.

    PubMed

    Maciel, Carolina B; Gilmore, Emily J

    2016-06-01

    In subarachnoid hemorrhage (SAH), seizures are frequent and occur at different time points, likely reflecting heterogeneous pathophysiology. Young patients, those with more severe SAH (by clot burden or presence of severe mental status changes at onset or focal neurologic deficits at any time), those with associated increased cortical irritation (by infarction or presence of underlying hematoma), and patients undergoing craniotomy are at higher risk. Advanced neurophysiologic monitoring allows for seizure burden quantification, identification of subclinical seizures, and interictal patterns as well as neurovascular complications that may have an independent impact on the outcome in this population. Practice regarding seizure prophylaxis varies widely; its institution is often guided by the risk-benefit ratio of seizures and medication side effects. Newer anticonvulsants seem to be equally effective and may have a more favorable profile. However, questions regarding the association of seizures and vasospasm, the therapeutic dosing, timing, and duration of antiepileptic treatment and the impact of seizures and antiepileptics on the outcome remain unanswered. In this review, we provide a broad overview of the work in this area and offer a diagnostic and therapeutic approach based on our own expert opinion.

  5. Treatment of seizures in subcortical laminar heterotopia with corpus callosotomy and lamotrigine.

    PubMed

    Vossler, D G; Lee, J K; Ko, T S

    1999-05-01

    Focal and generalized cortical dysgeneses are sometimes seen on the magnetic resonance images (MRI) of patients with epilepsy. Subcortical laminar heterotopia are bilateral collections of gray matter in the centrum semiovale that resemble a band or "double cortex" on MRI. We studied one male and two female patients with subcortical laminar heterotopia who had moderate to severe developmental delay, early-onset epilepsy, and medically refractory seizures. Atonic, atypical absence, tonic, myoclonic, complex partial, and generalized tonic-clonic seizures were recorded. Interictal and ictal electroencephalographic patterns were generalized and, less commonly, multifocal. Two years after corpus callosotomy, one patient was free of generalized tonic-clonic and atonic seizures, but the other patient who had undergone callosotomy had no significant reduction in seizure frequency. With lamotrigine treatment, the patient who had not had surgery had complete cessation of monthly episodes of status epilepticus and a dramatic reduction of generalized tonic-clonic seizures, and the other patient who received lamotrigine had a 50% reduction of her atonic seizures. In patients with subcortical laminar heterotopia, atonic and generalized tonic-clonic seizures can be substantially reduced or eliminated by corpus callosotomy or treatment with lamotrigine.

  6. Oral focal epithelial hyperplasia.

    PubMed

    Bassioukas, K; Danielides, V; Georgiou, I; Photos, E; Zagorianakou, P; Skevas, A

    2000-01-01

    Focal epithelial hyperplasia (FEH) or Heck disease, is a rare viral infection of the oral mucosa caused by HPV 13 or HPV 32. In Caucasians there have been only a few cases reported. We present the first case in Greece in a young Caucasian girl in which HPV 13 was detected with PCR analysis. The patient was successfully treated with CO2 laser.

  7. 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

  8. Psychomotor seizures, Penfield, Gibbs, Bailey and the development of anterior temporal lobectomy: A historical vignette

    PubMed Central

    Vannemreddy, Prasad; Stone, James L.; Vannemreddy, Siddharth; Slavin, Konstantin V.

    2010-01-01

    Psychomotor seizures, referred to as limbic or partial complex seizures, have had an interesting evolution in diagnosis and treatment. Hughlings Jackson was the first to clearly relate the clinical syndrome and likely etiology to lesions in the uncinate region of the medial temporal lobe. With the application of electroencephalography (EEG) to the study of human epilepsy as early as 1934 by Gibbs, Lennox, and Davis in Boston, electrical recordings have significantly advanced the study of epilepsy. In 1937, Gibbs and Lennox proposed the term "psychomotor epilepsy" to describe a characteristic EEG pattern of seizures accompanied by mental, emotional, motor, and autonomic phenomena. Concurrently, typical psychomotor auras and dreamy states were produced by electrical stimulation of medial temporal structures during epilepsy surgery by Penfield in Montreal. In 1937, Jasper joined Penfield, EEG was introduced and negative surgical explorations became less frequent. Nevertheless, Penfield preferred to operate only on space occupying lesions. A milestone in psychomotor seizure diagnosis was in the year 1946 when Gibbs, at the Illinois Neuropsychiatric Institute, Chicago, reported that the patient falling asleep during EEG was a major activator of the psychomotor discharges and electrographic ictal episodes becoming more prominently recorded. Working with Percival Bailey, Gibbs was proactive in applying EEG to define surgical excision of the focus in patients with intractable psychomotor seizures. By early 1950s, the Montreal group began to clearly delineate causative medial temporal lesions such as hippocampal sclerosis and tumors in the production of psychomotor seizures. PMID:20814492

  9. Hippocampal Inactivation Enhances Taste Learning

    ERIC Educational Resources Information Center

    Stone, Martha E.; Grimes, Brandon S.; Katz, Donald B.

    2005-01-01

    Learning tasks are typically thought to be either hippocampal-dependent (impaired by hippocampal lesions) or hippocampal-independent (indifferent to hippocampal lesions). Here, we show that conditioned taste aversion (CTA) learning fits into neither of these categories. Rats were trained to avoid two taste stimuli, one novel and one familiar.…

  10. A minimum of 3 months of dietary fish oil supplementation is required to raise amygdaloid afterdischarge seizure thresholds in rats--implications for treating complex partial seizures.

    PubMed

    Taha, Ameer Y; Trepanier, Marc-Olivier; Ciobanu, Flaviu A; Taha, Nadeen M; Ahmed, Muaz; Zeng, Qiudi; Cheuk, Waiyin I; Ip, Bryan; Filo, Elvis; Scott, Brian W; Burnham, W M; Bazinet, Richard P

    2013-04-01

    Complex partial seizures, which typically originate in limbic structures such as the amygdala, are often resistant to antiseizure medications. Our goal was to investigate the effects of chronic dietary supplementation with n-3 polyunsaturated fatty acids (PUFAs) derived from fish oil on seizure thresholds in the amygdala, as well as on blood and brain PUFA levels. The acute effects of injected n-3 PUFAs--eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)--were also tested in the maximal pentylenetetrazol (PTZ) seizure model. In amygdala-implanted subjects, fish oil supplementation significantly increased amygdaloid afterdischarge thresholds, as compared with controls at 3, 5, and 7 months after the start of supplementation. Fish oil supplementation also increased serum EPA and DHA concentrations. DHA concentration in the pyriform-amygdala area increased in the fish-oil treated group by 17-34%, but this effect did not reach statistical significance (P=0.065). DHA significantly increased the latency to seizure onset in the PTZ seizure model, whereas EPA had no significant effect. These observations suggest that chronic dietary fish oil supplementation can raise focal amygdaloid seizure thresholds and that this effect is likely mediated by DHA rather than by EPA.

  11. Hyponatraemia and seizures after ecstasy use.

    PubMed

    Holmes, S B; Banerjee, A K; Alexander, W D

    1999-01-01

    A patient presented to our unit with seizures and profound hyponatraemia after ingestion of a single tablet of ecstasy. The seizures proved resistant to therapy and ventilation on the intensive care unit was required. Resolution of the seizures occurred on correction of the metabolic abnormalities. The pathogenesis of seizures and hyponatraemia after ecstasy use is discussed. Ecstasy use should be considered in any young patient presenting with unexplained seizures and attention should be directed towards electrolyte levels, particularly sodium.

  12. Different patterns of dipole source localization in gelastic seizure with or without a sense of mirth.

    PubMed

    Iwasa, Hiroto; Shibata, Tadahiko; Mine, Seiichiro; Koseki, Keijirou; Yasuda, Kimiko; Kasagi, Yasufumi; Okada, Motohiro; Yabe, Hirooki; Kaneko, Sunao; Nakajima, Yoshio

    2002-05-01

    Dipole source localization corresponding to interictal spikes were estimated using EEG dipole tracing with a realistic three-shell head model in three patients with cryptogenic gelastic epilepsy. The dipole sources in two patients, whose gelastic seizures were accompanied by a subjective feeling of mirth, were estimated in the right or left medio-basal temporal regions. In the other patient, with gelastic seizures without a sense of mirth, the dipole sources were localized in the right frontal region corresponding to the anterior cingulate. The results suggest that the neural activities in hippocampal regions are involved with the generation of gelastic seizures with a sense of mirth and those in the cingulate might be associated with the motor act of laughter.

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

    PubMed Central

    MacKenzie, Georgina; Maguire, Jamie

    2014-01-01

    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 (30 mins/day for 14 consecutive days) exhibit an increase in serum corticosterone levels which is associated with increased susceptibility to seizures induced with kainic acid (20 mg/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

  14. Acute seizure suppression by transcranial direct current stimulation in rats

    PubMed Central

    Dhamne, Sameer C; Ekstein, Dana; Zhuo, Zhihong; Gersner, Roman; Zurakowski, David; Loddenkemper, Tobias; Pascual-Leone, Alvaro; Jensen, Frances E; Rotenberg, Alexander

    2015-01-01

    Objective Cathodal transcranial direct current stimulation (tDCS) is a focal neuromodulation technique that suppresses cortical excitability by low-amplitude constant electrical current, and may have an antiepileptic effect. Yet, tDCS has not been tested in status epilepticus (SE). Furthermore, a combined tDCS and pharmacotherapy antiseizure approach is unexplored. We therefore examined in the rat pentylenetetrazol (PTZ) SE model whether cathodal tDCS (1) suppresses seizures, (2) augments lorazepam (LZP) efficacy, and (3) enhances GABAergic cortical inhibition. Methods Experiment 1 aimed to identify an effective cathodal tDCS intensity. Rats received intraperitoneal PTZ followed by tDCS (sham, cathodal 1 mA, or cathodal 0.1 mA; for 20 min), and then a second PTZ challenge. In Experiment 2, two additional animal groups received a subtherapeutic LZP dose after PTZ, and then verum or sham tDCS. Clinical and electroencephalography (EEG) epileptic activity were compared between all groups. In Experiment 3, we measured GABA-mediated paired-pulse inhibition of the motor evoked potential by paired-pulse transcranial magnetic stimulation (ppTMS) in rats that received PTZ or saline, and either verum or sham tDCS. Results Cathodal 1 mA tDCS (1) reduced EEG spike bursts, and suppressed clinical seizures after the second PTZ challenge, (2) in combination with LZP was more effective in seizure suppression and improved the clinical seizure outcomes compared to either tDCS or LZP alone, and (3) prevented the loss of ppTMS motor cortex inhibition that accompanied PTZ injection. Interpretation These results suggest that cathodal 1 mA tDCS alone and in combination with LZP can suppress seizures by augmenting GABAergic cortical inhibition. PMID:26339678

  15. Preictal Dynamics of EEG Complexity in Intracranially Recorded Epileptic Seizure

    PubMed Central

    Bob, Petr; Roman, Robert; Svetlak, Miroslav; Kukleta, Miloslav; Chladek, Jan; Brazdil, Milan

    2014-01-01

    Abstract Recent findings suggest that neural complexity reflecting a number of independent processes in the brain may characterize typical changes during epileptic seizures and may enable to describe preictal dynamics. With respect to previously reported findings suggesting specific changes in neural complexity during preictal period, we have used measure of pointwise correlation dimension (PD2) as a sensitive indicator of nonstationary changes in complexity of the electroencephalogram (EEG) signal. Although this measure of complexity in epileptic patients was previously reported by Feucht et al (Applications of correlation dimension and pointwise dimension for non-linear topographical analysis of focal onset seizures. Med Biol Comput. 1999;37:208–217), it was not used to study changes in preictal dynamics. With this aim to study preictal changes of EEG complexity, we have examined signals from 11 multicontact depth (intracerebral) EEG electrodes located in 108 cortical and subcortical brain sites, and from 3 scalp EEG electrodes in a patient with intractable epilepsy, who underwent preoperative evaluation before epilepsy surgery. From those 108 EEG contacts, records related to 44 electrode contacts implanted into lesional structures and white matter were not included into the experimental analysis. The results show that in comparison to interictal period (at about 8–6 minutes before seizure onset), there was a statistically significant decrease in PD2 complexity in the preictal period at about 2 minutes before seizure onset in all 64 intracranial channels localized in various brain sites that were included into the analysis and in 3 scalp EEG channels as well. Presented results suggest that using PD2 in EEG analysis may have significant implications for research of preictal dynamics and prediction of epileptic seizures. PMID:25415671

  16. Using Lorenz plot and Cardiac Sympathetic Index of heart rate variability for detecting seizures for patients with epilepsy.

    PubMed

    Jeppesen, Jesper; Beniczky, Sandor; Johansen, Peter; Sidenius, Per; Fuglsang-Frederiksen, Anders

    2014-01-01

    Tachycardia is often seen during epileptic seizures, but it also occurs during physical exercise. In order to assess whether focal epileptic seizures can be detected by short term moving window Heart Rate Variability (HRV) analysis, we modified the geometric HRV method, Lorenz plot, to consist of only 30, 50 or 100 R-R intervals per analyzed window. From each window we calculated the longitudinal (L) and transverse (T) variability of Lorenz plot to retrieve the Cardiac Sympathetic Index (CSI) as (L/T) and "Modified CSI" (described in methods), and compared the maximum during the patient's epileptic seizures with that during the patient's own exercise and non-seizure sessions as control. All five analyzed patients had complex partial seizures (CPS) originating in the temporal lobe (11 seizures) during their 1-5 days long term video-EEG monitoring. All CPS with electroencephalographic correlation were selected for the HRV analysis. The CSI and Modified CSI were correspondently calculated after each heart beat depicting the prior 30, 50 and 100 R-R intervals at the time. CSI (30, 50 and 100) and Modified CSI (100) showed a higher maximum peak during seizures than exercise/non-seizure (121-296%) for 4 of the 5 patients within 4 seconds before till 60 seconds after seizure onset time even though exercise maximum HR exceeded that of the seizures. The results indicate a detectable, sudden and inordinate shift towards sympathetic overdrive in the sympathovagal balance of the autonomic nervous system just around seizure-onset for certain patients. This new modified moving window Lorenz plot method seems promising way of constructing a portable ECG-based epilepsy alarm for certain patients with epilepsy who needs aid during seizure.

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

    PubMed

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

    2013-10-01

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

  18. Oral focal epithelial hyperplasia.

    PubMed

    López-Jornet, Pía; Camacho-Alonso, Fabio; Berdugo, Lucero

    2010-01-01

    Focal epithelial hyperplasia (FEH) is a benign, asymptomatic disease. It appears as papules, principally on the lower lip, although it can also be found on the retro-commissural mucosa and tongue and, less frequently, on the upper lip, gingiva and palate. FEH is caused by human papillomavirus subtype 13 or 32. The condition occurs in many populations and ethnic groups. We present the clinical case of a 31-year-old male with lesions that clinically and histologically corresponded to FEH.

  19. Updating the lamellar hypothesis of hippocampal organization.

    PubMed

    Sloviter, Robert S; Lømo, Terje

    2012-01-01

    Andersen et al. (1971) proposed that excitatory activity in the entorhinal cortex propagates topographically to the dentate gyrus, and on through a "trisynaptic circuit" lying within transverse hippocampal "slices" or "lamellae." In this way, a relatively simple structure might mediate complex functions in a manner analogous to the way independent piano keys can produce a nearly infinite variety of unique outputs. The lamellar hypothesis derives primary support from the "lamellar" distribution of dentate granule cell axons (the mossy fibers), which innervate dentate hilar neurons and area CA3 pyramidal cells and interneurons within the confines of a thin transverse hippocampal segment. Following the initial formulation of the lamellar hypothesis, anatomical studies revealed that unlike granule cells, hilar mossy cells, CA3 pyramidal cells, and Layer II entorhinal cells all form axonal projections that are more divergent along the longitudinal axis than the clearly "lamellar" mossy fiber pathway. The existence of pathways with "translamellar" distribution patterns has been interpreted, incorrectly in our view, as justifying outright rejection of the lamellar hypothesis (Amaral and Witter, 1989). We suggest that the functional implications of longitudinally projecting axons depend not on whether they exist, but on what they do. The observation that focal granule cell layer discharges normally inhibit, rather than excite, distant granule cells suggests that longitudinal axons in the dentate gyrus may mediate "lateral" inhibition and define lamellar function, rather than undermine it. In this review, we attempt a reconsideration of the evidence that most directly impacts the physiological concept of hippocampal lamellar organization.

  20. Neurophysiological aspects of neonatal seizures.

    PubMed

    Watanabe, Kazuyoshi

    2014-05-01

    Recently, amplitude-integrated EEG (aEEG) has been increasingly used and proved useful in neonatal intensive care units (NICU) for the management of neonatal seizures. It does not replace, but is supplementary to standard EEG. This article reviews some of findings obtained with standard EEGs, and tries to interpret them with recent findings in the field of basic science. Seizures mainly occur in active-REM sleep in neonates. This is in sharp contrast to those in older children and adults, in whom epileptic seizures occur mainly in NREM sleep. This may be explained by neurotransmitter effects on sleep mechanisms of the neonatal brain that are different from those of older individuals. When all clinical seizures have no electrical correlates, they are non-epileptic, but when the correlation between clinical seizures and frequent electrical discharges are inconsistent, they should rather be considered epileptic, reflecting progression of status epilepticus causing electro-clinical dissociation. Electro-clinical dissociation is not a characteristic of neonatal seizures per se, but a feature of prolonged status epilepticus in adults as well as children. It occurs when prolonged status epilepticus itself causes a progressively severe encephalopathy, or when status occurs in the presence of a severe underlying encephalopathy. In neonates without pre-existing brain damage, frequent seizures per se may cause mild depression characterized by the loss of high voltage slow patterns, an important constituent of slow wave sleep reflecting cortico-cortical connectivity. Mild depression only in the acute stage is not associated with neurological sequelae, but previously damaged brain may be more vulnerable than normal brain.

  1. Prevalence of Stroke in Neonates Who Admitted With Seizures in Neonatal Intensive Care Unit

    PubMed Central

    FARHADI, Roya; ALAEE, Abdolrasool; ALIPOUR, Zahra; ABBASKHANIAN, Ali; NAKHSHAB, Maryam; DERAKHSHANFAR, Hojjat

    2015-01-01

    Objective Prevalence of neonatal stroke has been reported 1/2300-1/4000 live births and accounts for 12-20% of the cases of neonatal seizures. Although stroke has been introduced as the second cause of the neonatal seizures in literatures, it may remain unclear in diagnostic evaluations of seizure in neonates. This study was performed to assess the prevalence of stroke in neonates with seizure. Materials & Methods In this cross-sectional study, all neonates ≥ 28 weeks of gestation with a diagnosis of seizures admitted to the NICU of Boo-Ali Sina Hospital in Sari, north of Iran, were enrolled. Brain CT scan and a Transcranial Doppler ultrasonography were performed for the all cases. In cases that stroke were reported in one or two above modalities, an MRI was also performed and prevalence of stroke was reported. Putative risk factors of stroke were analyzed with univariate and multivariate statistical methods. Results From 174 newborn infants, 75.3% of neonates were male. Prevalence of stroke was 8%, 2.3% and 3.4% in Doppler ultrasonography, CT scan and MRI reports respectively. Umbilical venous catheterization was the risk factor of stroke in the univariate and multivariate analysis (P= 0.001; OR, 10.39; 95% CI, 2.72- 39.77). The most common form of seizure was focal clonic seizures (78.6%) in neonates with stroke. Conclusion Investigation of stroke as an etiology of neonatal seizures is essential because seizure may be the only symptom of neonatal cerebral infarction. Doppler ultrasonography can be a valuable diagnostic tool at first in critically ill neonates or in situations that MRI is not available primarily. Further studies with notice to outcome assessment of these infants recommended. PMID:26664440

  2. Seizures and Meperidine: Overstated and Underutilized.

    PubMed

    Schlick, Konrad H; Hemmen, Thomas M; Lyden, Patrick D

    2015-12-01

    Meperidine is used for pain control and treatment of shivering. Concerns about neurotoxicity, particularly seizures, have led to efforts limiting meperidine use. We reviewed the body of evidence linking meperidine to seizures. We searched PubMed for the terms meperidine, normeperidine, pethidine, and norpethidine; each was combined with the terms: seizure, epilepsy, epileptogenic, toxicity, overdose, seizure threshold, and convulsion. Articles were assessed for relevance. Semiologies were reviewed to ascertain seizure likelihood. Our search yielded 351 articles, of which 66 were relevant. Of these, 33 had primary clinical data on meperidine-associated seizures, comprising 50 patients. Twenty events were deemed likely to be seizures, 26 indeterminate, and 4 unlikely. Most studies were case reports. Confounding comorbidities were frequent. The evidence base for meperidine-associated seizures in man is scant. Seizure risk associated with meperidine appears to be overstated. The utility of meperidine should continue to be explored, especially for therapeutic hypothermia.

  3. Gelastic seizures in ring chromosome 20 syndrome: a case report with video illustration.

    PubMed

    Dimova, Petia; Boneva, Iliyana; Todorova, Albena; Minotti, Lorella; Kahane, Philippe

    2012-06-01

    Although increasingly recognised, ring chromosome 20 (r[20]) syndrome is still diagnosed with delay, sometimes leading to inappropriate presurgical evaluation. The focal, presumed frontal, character of the seizures manifesting with fear and hypermotor behaviour and episodes of non-convulsive status epilepticus (NCSE) are most typical, as well as cognitive impairment with behavioural problems and, sometimes, dysmorphic signs. We present a girl diagnosed at the age of 13 years who suffered from an atypical clinical presentation, with minimal cognitive problems, absence of dysmorphic symptoms, and hypermotor/gelastic seizures. [Published with video sequences].

  4. Predictors of anti-convulsant treatment failure in children presenting with malaria and prolonged seizures in Kampala, Uganda

    PubMed Central

    Mpimbaza, Arthur; Staedke, Sarah G; Ndeezi, Grace; Byarugaba, Justus; Rosenthal, Philip J

    2009-01-01

    Background In endemic areas, falciparum malaria remains the leading cause of seizures in children presenting to emergency departments. In addition, seizures in malaria have been shown to increase morbidity and mortality in these patients. The management of seizures in malaria is sometimes complicated by the refractory nature of these seizures to readily available anti-convulsants. The objective of this study was to determine predictors of anti-convulsant treatment failure and seizure recurrence after initial control among children with malaria. Methods In a previous study, the efficacy and safety of buccal midazolam was compared to that of rectal diazepam in the treatment of prolonged seizures in children aged three months to 12 years in Kampala, Uganda. For this study, predictive models were used to determine risk factors for anti-convulsant treatment failure and seizure recurrence among the 221 of these children with malaria. Results Using predictive models, focal seizures (OR 3.21; 95% CI 1.42–7.25, p = 0.005), cerebral malaria (OR 2.43; 95% CI 1.20–4.91, p = 0.01) and a blood sugar ≥200 mg/dl at presentation (OR 2.84; 95% CI 1.11–7.20, p = 0.02) were independent predictors of treatment failure (seizure persistence beyond 10 minutes or recurrence within one hour of treatment). Predictors of seizure recurrence included: 1) cerebral malaria (HR 3.32; 95% CI 1.94–5.66, p < 0.001), 2) presenting with multiple seizures (HR 2.45; 95% CI 1.42–4.23, p = 0.001), 3) focal seizures (HR 2.86; 95% CI 1.49–5.49, p = 0.002), 4) recent use of diazepam (HR 2.43; 95% CI 1.19–4.95, p = 0.01) and 5) initial control of the seizure with diazepam (HR 1.96; 95% CI 1.16–3.33, p = 0.01). Conclusion Specific predictors, including cerebral malaria, can identify patients with malaria at risk of anti-convulsant treatment failure and seizure recurrence. PMID:19563665

  5. N-methyl-D-aspartate, hyperpolarization-activated cation current (Ih) and gamma-aminobutyric acid conductances govern the risk of epileptogenesis following febrile seizures in rat hippocampus.

    PubMed

    Ouardouz, Mohamed; Lema, Pablo; Awad, Patricia N; Di Cristo, Graziella; Carmant, Lionel

    2010-04-01

    Febrile seizures are the most common types of seizure in children, and are generally considered to be benign. However, febrile seizures in children with dysgenesis have been associated with the development of temporal lobe epilepsy. We have previously shown in a rat model of dysgenesis (cortical freeze lesion) and hyperthermia-induced seizures that 86% of these animals developed recurrent seizures in adulthood. The cellular changes underlying the increased risk of epileptogenesis in this model are not known. Using whole cell patch-clamp recordings from CA1 hippocampal pyramidal cells, we found a more pronounced increase in excitability in rats with both hyperthermic seizures and dysgenesis than in rats with hyperthermic seizures alone or dysgenesis alone. The change was found to be secondary to an increase in N-methyl-D-aspartate (NMDA) receptor-mediated excitatory postsynaptic currents (EPSCs). Inversely, hyperpolarization-activated cation current was more pronounced in naïve rats with hyperthermic seizures than in rats with dysgenesis and hyperthermic seizures or with dysgenesis alone. The increase in GABAA-mediated inhibition observed was comparable in rats with or without dysgenesis after hyperthermic seizures, whereas no changes were observed in rats with dysgenesis alone. Our work indicates that in this two-hit model, changes in NMDA receptor-mediated EPSCs may facilitate epileptogenesis following febrile seizures. Changes in the hyperpolarization-activated cation currents may represent a protective reaction and act by damping the NMDA receptor-mediated hyperexcitability, rather than converting inhibition into excitation. These findings provide a new hypothesis of cellular changes following hyperthermic seizures in predisposed individuals, and may help in the design of therapeutic strategies to prevent epileptogenesis following prolonged febrile seizures.

  6. Hippocampal neurons in schizophrenia

    PubMed Central

    Heckers, S.; Konradi, C.

    2014-01-01

    Summary The hippocampus is crucial for normal brain function, especially for the encoding and retrieval of multimodal sensory information. Neuropsychiatric disorders such as temporal lobe epilepsy, amnesia, and the dementias are associated with structural and functional abnormalities of specific hippocampal neurons. More recently we have also found evidence for a role of the hippocampus in the pathophysiology of schizophrenia. The most consistent finding is a subtle, yet significant volume difference in schizophrenia. Here we review the cellular and molecular basis of smaller hippocampal volume in schizophrenia. In contrast to neurodegenerative disorders, total hippocampal cell number is not markedly decreased in schizophrenia. However, the intriguing finding of a selective loss of hippocampal inter-neurons deserves further study. Two neurotransmitter receptors, the GABAA and AMPA/kainate glutamate receptors, appear to be abnormal, whereas changes of the NMDA glutamate receptor are less robust. The expression of several genes, including those related to the GABAergic system, neurodevelopment, and synaptic function, is decreased in schizophrenia. Taken together, recent studies of hippocampal cell number, protein expression, and gene regulation point towards an abnormality of hippocampal architecture in schizophrenia. PMID:12111476

  7. Seizures in the critically ill.

    PubMed

    Ch'ang, J; Claassen, J

    2017-01-01

    Critically ill patients with seizures are either admitted to the intensive care unit because of uncontrolled seizures requiring aggressive treatment or are admitted for other reasons and develop seizures secondarily. These patients may have multiorgan failure and severe metabolic and electrolyte disarrangements, and may require complex medication regimens and interventions. Seizures can be seen as a result of an acute systemic illness, a primary neurologic pathology, or a medication side-effect and can present in a wide array of symptoms from convulsive activity, subtle twitching, to lethargy. In this population, untreated isolated seizures can quickly escalate to generalized convulsive status epilepticus or, more frequently, nonconvulsive status epileptics, which is associated with a high morbidity and mortality. Status epilepticus (SE) arises from a failure of inhibitory mechanisms and an enhancement of excitatory pathways causing permanent neuronal injury and other systemic sequelae. Carrying a high 30-day mortality rate, SE can be very difficult to treat in this complex setting, and a portion of these patients will become refractory, requiring narcotics and anesthetic medications. The most significant factor in successfully treating status epilepticus is initiating antiepileptic drugs as soon as possible, thus attentiveness and recognition of this disease are critical.

  8. Automated seizure detection systems and their effectiveness for each type of seizure.

    PubMed

    Ulate-Campos, A; Coughlin, F; Gaínza-Lein, M; Fernández, I Sánchez; Pearl, P L; Loddenkemper, T

    2016-08-01

    Epilepsy affects almost 1% of the population and most of the approximately 20-30% of patients with refractory epilepsy have one or more seizures per month. Seizure detection devices allow an objective assessment of seizure frequency and a treatment tailored to the individual patient. A rapid recognition and treatment of seizures through closed-loop systems could potentially decrease morbidity and mortality in epilepsy. However, no single detection device can detect all seizure types. Therefore, the choice of a seizure detection device should consider the patient-specific seizure semiologies. This review of the literature evaluates seizure detection devices and their effectiveness for different seizure types. Our aim is to summarize current evidence, offer suggestions on how to select the most suitable seizure detection device for each patient and provide guidance to physicians, families and researchers when choosing or designing seizure detection devices. Further, this review will guide future prospective validation studies.

  9. Effects of A1 receptor agonist/antagonist on spontaneous seizures in pilocarpine-induced epileptic rats.

    PubMed

    Amorim, Beatriz Oliveira; Hamani, Clement; Ferreira, Elenn; Miranda, Maísa Ferreira; Fernandes, Maria José S; Rodrigues, Antonio M; de Almeida, Antônio-Carlos G; Covolan, Luciene

    2016-08-01

    Adenosine is an endogenous anticonvulsant that activates pre- and postsynaptic adenosine A1 receptors. A1 receptor agonists increase the latency for the development of seizures and status epilepticus following pilocarpine administration. Although hippocampal adenosine is increased in the chronic phase of the pilocarpine model, it is not known whether the modulation of A1 receptors may influence the frequency of spontaneous recurrent seizures (SRS). Here, we tested the hypothesis that the A1 receptor agonist RPia ([R]-N-phenylisopropyladenosine) and the A1 antagonist DPCPX (8-Cyclopentyl-1,3-dipropylxanthine) administered to chronic pilocarpine epileptic rats would respectively decrease and increase the frequency of SRS and hippocampal excitability. Four months after Pilo-induced SE, chronic epileptic rats were video-monitored for the recording of SRS before (basal) and after a 2-week treatment with RPia (25μg/kg) or DPCPX (50μg/kg). Following sacrifice, brain slices were studied with electrophysiology. We found that rats given RPia had a 93% nonsignificant reduction in the frequency of seizures compared with their own pretreatment baseline. In contrast, the administration of DPCPX resulted in an 87% significant increase in seizure rate. Nontreated epileptic rats had a similar frequency of seizures along the study. Corroborating our behavioral data, in vitro recordings showed that slices from animals previously given DPCPX had a shorter latency to develop epileptiform activity, longer and higher DC shifts, and higher spike amplitude compared with slices from nontreated Pilo controls. In contrast, smaller spike amplitude was recorded in slices from animals given RPia. In summary, the administration of A1 agonists reduced hippocampal excitability but not the frequency of spontaneous recurrent seizures in chronic epileptic rats, whereas A1 receptor antagonists increased both.

  10. Neurologic links between epilepsy and depression in women: is hippocampal neuroplasticity the key?

    PubMed

    Hajszan, Tibor; MacLusky, Neil J

    2006-03-28

    Recent advances in our understanding of the actions of sex steroids on the brain and the pathophysiology of depression have provided a hypothetical framework that may functionally connect epilepsy, ovarian hormone levels, and depression. The hippocampus plays a critical role in both seizure activity and mood disorders, which suggests that pathology in this area of the brain might provide a link between epilepsy and depression. Recent findings support the view that neurogenesis is not the only factor that contributes to the pathomechanism of depression and antidepressant responses, which may involve other hippocampal cellular or molecular changes, or both. Specifically, remodeling of the hippocampal spine synapses may play a significant role in the neurobiology of depression and the effects of antidepressant therapy. Because the effects of estrogens on hippocampal synaptogenesis parallel those of antidepressants, loss of estrogen appears to be a critical contributor to the etiology of depressive disorders. The increased incidence of depression observed in women with epilepsy might therefore reflect a hormonal deficiency state because epilepsy is frequently associated with defects in reproductive function. In women with catamenial epilepsy, changes in gonadal steroid production are seen to link seizure frequency with reproductive state, emphasizing the importance of gonadal steroid levels not only in depression but also in seizure activity. Paradoxical features of epilepsy, i.e., seizure-induced increases in hippocampal neurotrophin expression and neurogenesis, suggest that the most important factor in the neurobiology of depression might be the extent to which the hippocampus can adapt appropriately to changes in the environment through alterations in hippocampal synaptic connectivity.

  11. Interictal spikes, seizures and ictal cell death are not necessary for post-traumatic epileptogenesis in vitro

    PubMed Central

    Berdichevsky, Yevgeny; Dzhala, Volodymyr; Mail, Michelle; Staley, Kevin J.

    2012-01-01

    Clinical studies indicate that phenytoin prevents acute post-traumatic seizures but not subsequent post-traumatic epilepsy. We explored this phenomenon using organotypic hippocampal slice cultures as a model of severe traumatic brain injury. Hippocampal slices were cultured for up to eight weeks, during which acute and chronic electrical recordings revealed a characteristic evolution of spontaneous epileptiform discharges, including interictal spikes, seizure activity and electrical status epilepticus. Cell death exhibited an early peak immediately following slicing, and a later secondary peak that coincided with the peak of seizure-like activity. The secondary peak in neuronal death was abolished by either blockade of glutamatergic transmission with kynurenic acid or by elimination of ictal activity and status epilepticus with phenytoin. Withdrawal of kynurenic acid or phenytoin was followed by a sharp increase in spontaneous seizure activity. Phenytoin’s anticonvulsant and neuroprotective effects failed after four weeks of continuous administration. These data support the clinical findings that after brain injury, anticonvulsants prevent seizures but not epilepsy or the development of anticonvulsant resistance. We extend the clinical data by showing that secondary neuronal death is correlated with ictal but not interictal activity, and that blocking all three of these sequelae of brain injury does not prevent epileptogenesis in this in vitro model. PMID:22115940

  12. [Seizures revealing phosphocalcic metabolism abnormalities].

    PubMed

    Hmami, F; Chaouki, S; Benmiloud, S; Souilmi, F Z; Abourazzak, S; Idrissi, M; Atmani, S; Bouharrou, A; Hida, M

    2014-01-01

    Hypocalcemia due to hypoparathyroidism produces a broad spectrum of clinical manifestations, but overt symptoms may be sparse. One unusual presentation is onset or aggravation of epilepsy in adolescence revealing hypoparathyroidism. This situation can lead to delayed diagnosis, with inefficacity of the antiepileptic drugs. We report five cases of adolescence-onset epilepsy with unsuccessful antiepileptic therapy, even with gradually increasing dose. Physical examination revealed signs of hypocalcemia, confirmed biologically. Full testing disclosed the origin of the seizures: hypoparathyroidism in three patients and pseudohypoparathyroidism in the other two. In four of five patients, computed tomography showed calcification of the basal ganglia, defining Fahr's syndrome. The patients were treated with oral calcium and active vitamin D (1-alphahydroxy vitamin D3). Seizure frequency progressively decreased and serum calcium levels returned to normal. These cases illustrate the importance of the physical examination and of routine serum calcium assay in patients with new-onset epileptic seizures in order to detect hypocalcemia secondary to hypoparathyroidism.

  13. [Focal epithelial hyperplasia].

    PubMed

    Delgado, Yolanda; Torrelo, Antonio; Colmenero, Isabel; Zambrano, Antonio

    2005-12-01

    Focal epithelial hyperplasia (FEH) is a benign proliferation of the oral mucosa with well defined clinical and histological characteristics. It has been associated with infection of the oral mucosa by types 13 and 32 of the human papillomavirus (HPV), and to a lesser extent, with other types. Its clinical course is variable, although it usually persists for months or years; cases with spontaneous resolution have been described, as have others with prolonged persistence. We present the case of an Ecuadorian boy whose visit was motivated by lesions in the oral mucosa consistent with a diagnosis of FEH, which were confirmed in the histological study, and in which HPV type 13 DNA was identified.

  14. Focal adhesions in osteoneogenesis

    PubMed Central

    Biggs, M.J.P; Dalby, M.J

    2010-01-01

    As materials technology and the field of tissue engineering advances, the role of cellular adhesive mechanisms, in particular the interactions with implantable devices, becomes more relevant in both research and clinical practice. A key tenet of medical device technology is to use the exquisite ability of biological systems to respond to the material surface or chemical stimuli in order to help develop next-generation biomaterials. The focus of this review is on recent studies and developments concerning focal adhesion formation in osteoneogenesis, with an emphasis on the influence of synthetic constructs on integrin mediated cellular adhesion and function. PMID:21287830

  15. Asynchronous electrical activity in epileptic seizures

    NASA Astrophysics Data System (ADS)

    Holman, Katherine; Lim, Eugene; Gliske, Stephen; Stacey, William; Fink, Christian

    High-frequency oscillations (HFOs) have been postulated to be potential biomarkers for focal epileptic seizures, with fast ripples (>250 Hz) as the most interesting candidate. The mechanisms underlying the generation of fast ripples, however, are not well understood. In this study, we draw upon results from previous computational studies on HFOs to develop a new mathematical model from first principles describing the generation of HFOs through asynchronous neuronal firing. Asynchrony in the model is obtained with the introduction of two parameters of heterogeneity: variability in the inter-spike interval (ISI) and jitter. The model predicts the generation of harmonic narrow-band oscillations if the heterogeneity-governing parameters do not differ from the predefined ISI by more than 20%. Comparisons against results from a separately constructed computational model verify the accuracy of the model in study. These results provide us with a rigorous framework in which we may investigate the mechanisms driving the generation of abnormal HFOs, and may serve as groundwork for future research in epileptogenesis. Nsf Grant 1003992, Ohio Wesleyan University SSRP.

  16. Inflammatory markers associated with seizures.

    PubMed

    Sohn, Hong Seok; Kim, Sung Keun; Lee, Seo-Young

    2016-03-01

    Seizures can produce systemic changes, including elevated body temperature, white blood cell count, and C-reactive protein levels, which raises concern for potential infection. We describe seizure-induced inflammation-like responses and discuss how these changes may be distinguished from those associated with infection. We prospectively investigated 140 consecutive visits to the emergency room, in which patients presented with seizures. We defined elevated body temperature, white blood cell count, or C-reactive protein levels as inflammation-like responses. We investigated the occurrence of inflammation-like responses, characteristics of the seizures, neurological status at the initial visit, outcomes, and clinical findings to determine the presence of infection. We ascertained whether the patients had infection or not based on the overall information post-discharge. An inflammation-like response was observed in 56.3% of all visits and 19.3% were diagnosed with concurrent infection. Among the visits with inflammation-like response, 34.7% were shown to have an infection. Increases in body temperature and C-reactive protein levels were milder (<39°C and <6 mg/dl, respectively) in patients without infection compared to those with infection, whereas there was no difference in leukocytosis, with regard to the presence or absence of infection. Increased body temperature occurred only in cases of generalized tonic-clonic seizures, whereas leukocytosis and elevated C-reactive protein levels were reported in patients with any type of seizure. Body temperatures returned to normal within eight hours in uncomplicated cases. Seizures frequently induce an increase in body temperature, white blood cell count, or C-reactive protein levels, making it challenging to distinguish these changes from those associated with infection. Nonetheless, elevated body temperature in the absence of generalized tonic-clonic seizures, above 39̊C, or persisting for more than eight hours after

  17. Utility of different seizure induction protocols in psychogenic nonepileptic seizures.

    PubMed

    Goyal, Gourav; Kalita, Jayantee; Misra, Usha K

    2014-08-01

    Psychogenic non epileptic seizure (PNES) can be induced by several induction tests but their relative usefulness has not been evaluated. In this study, we report the sensitivity and specificity of various induction tests in the diagnosis of PNES and assess their discomfort level. The induction tests were: (a) compression of temple region (CTR), (b) verbal suggestion (VS), (c) tuning fork application (TFA), (d) moist swab application (MSA), (e) torch light stimulation (TLS) and (f) saline injection (SI). Up to 3 trials were done for each test except for normal saline injection which was given once. For comparison of these tests, patients with epileptic seizures were included as controls. The time to precipitate PNES was recorded and patients' discomfort levels were noted on a 0-10 scale. Video EEG was recorded in the PNES patients. 140 patients with PNES and 50 controls with epileptic seizures were included. The diagnostic yield of CTR was 65.7%, TFA 61.4%, MSA 60.7%, SI 55.6%, VS 54.3% and TLS 40.7%. These tests did not induce seizures in the controls. All these tests had 100% specificity and 100% positive predictive value in the diagnosis of PNES. The maximum discomfort was reported with SI and minimum with MSA. The similarity of efficacy and discomfort with CTR and TFA appear to be the most optimal induction techniques when compared with VS, AMS, TLS, and SI.

  18. Seizure entrainment with polarizing low-frequency electric fields in a chronic animal epilepsy model

    NASA Astrophysics Data System (ADS)

    Sunderam, Sridhar; Chernyy, Nick; Peixoto, Nathalia; Mason, Jonathan P.; Weinstein, Steven L.; Schiff, Steven J.; Gluckman, Bruce J.

    2009-08-01

    Neural activity can be modulated by applying a polarizing low-frequency (Lt100 Hz) electric field (PLEF). Unlike conventional pulsed stimulation, PLEF stimulation has a graded, modulatory effect on neuronal excitability, and permits the simultaneous recording of neuronal activity during stimulation suitable for continuous feedback control. We tested a prototype system that allows for simultaneous PLEF stimulation with minimal recording artifact in a chronic tetanus toxin animal model (rat) of hippocampal epilepsy with spontaneous seizures. Depth electrode local field potentials recorded during seizures revealed a characteristic pattern of field postsynaptic potentials (fPSPs). Sinusoidal voltage-controlled PLEF stimulation (0.5-25 Hz) was applied in open-loop cycles radially across the CA3 of ventral hippocampus. For stimulated seizures, fPSPs were transiently entrained with the PLEF waveform. Statistical significance of entrainment was assessed with Thomson's harmonic F-test, with 45/132 stimulated seizures in four animals individually demonstrating significant entrainment (p < 0.04). Significant entrainment for multiple presentations at the same frequency (p < 0.01) was observed in three of four animals in 42/64 stimulated seizures. This is the first demonstration in chronically implanted freely behaving animals of PLEF modulation of neural activity with simultaneous recording.

  19. Multiple Sclerosis: Can It Cause Seizures?

    MedlinePlus

    ... it cause seizures? Is there any connection between multiple sclerosis and epilepsy? Answers from B Mark Keegan, M. ... seizures are more common in people who have multiple sclerosis (MS) than in those who don't have ...

  20. Focal Epileptogenic Lesions in Adult Patients with Epilepsy and Generalized Epileptiform Discharges

    PubMed Central

    Kim, Dong Wook; Lee, Seo-Young; Lee, Sang Kun

    2016-01-01

    Background and Purpose There are reports of successful resective epilepsy surgery for pediatric patients with epilepsy and generalized epileptiform discharges when they had focal epileptogenic lesions identified by MRI. However, there is limited information regarding adult patients with epilepsy who have both generalized epileptiform discharges and focal epileptogenic lesions. Methods To investigate the incidence and characteristics of adult patients who have both generalized epileptiform discharges and potentially epileptogenic lesions, we retrospectively analyzed data of clinical features and results of EEG and MRI of all patients with adult-onset epilepsy in a tertiary referral hospital. Results While 1315 patients were classified as having partial seizures, 207 patients were classified as having generalized seizures. Five of 207 patients (2.4%) with generalized seizures had potentially epileptogenic lesions. All the epileptogenic lesions were congenital or acquired during early life, such as focal cortical dysplasia, dysembryoplastic neuroepithelial tumor, and cerebromalacic change because of perinatal injury. Conclusions The presence of epileptogenic lesions in adult patients with generalized epileptiform discharges may be an incidental finding, but it has been suggested that some adult-onset epilepsy with generalized epileptiform discharges may actually have focal onset, which may have significant clinical implications for the choice of appropriate treatment. PMID:28101478

  1. Impaired K+ Homeostasis and Altered Electrophysiological Properties of Post-Traumatic Hippocampal Glia

    PubMed Central

    D'Ambrosio, Raimondo; Maris, Donald O.; Grady, M. Sean; Winn, H. Richard; Janigro, Damir

    2014-01-01

    Traumatic brain injury (TBI) can be associated with memory impairment, cognitive deficits, or seizures, all of which can reflect altered hippocampal function. Whereas previous studies have focused on the involvement of neuronal loss in post-traumatic hippocampus, there has been relatively little understanding of changes in ionic homeostasis, failure of which can result in neuronal hyperexcitability and abnormal synchronization. Because glia play a crucial role in the homeostasis of the brain microenvironment, we investigated the effects of TBI on rat hippocampal glia. Using a fluid percussion injury (FPI) model and patch-clamp recordings from hippocampal slices, we have found impaired glial physiology 2 d after FPI. Electrophysiologically, we observed reduction in transient outward and inward K+ currents. To assess the functional consequences of these glial changes, field potentials and extracellular K+ activity were recorded in area CA3 during antidromic stimulation. An abnormal extracellular K+ accumulation was observed in the post-traumatic hippocampal slices, accompanied by the appearance of CA3 afterdischarges. After pharmacological blockade of excitatory synapses and of K+ inward currents, uninjured slices showed the same altered K+ accumulation in the absence of abnormal neuronal activity. We suggest that TBI causes loss of K+ conductance in hippocampal glia that results in the failure of glial K+ homeostasis, which in turn promotes abnormal neuronal function. These findings provide a new potential mechanistic link between traumatic brain injury and subsequent development of disorders such as memory loss, cognitive decline, seizures, and epilepsy. PMID:10479715

  2. Frontal lobe nonconvulsive status epilepticus: a case of epileptic stuttering, aphemia, and aphasia--not a sign of psychogenic nonepileptic seizures.

    PubMed

    Kaplan, Peter W; Stagg, Ryan

    2011-06-01

    Stuttering is a repetitive, iterative disfluency of speech, and is usually seen as a developmental problem in childhood. Acquired causes in adults include strokes and medications. When stuttering occurs with seizure-like events, it is usually attributed to psychogenic nonepileptic seizures. We describe an elderly man who experienced personality change and bouts of stuttering, followed by anarthria with preserved writing and then aphasia affecting written and uttered language, and ending with confusion. EEG recordings showed nonconvulsive status epilepticus (NCSE) with focality in the left frontal region followed by bifrontal NCSE. This case enlarges our understanding of the behavioral correlates of focal frontal seizures to include simple partial seizures with speech and then language output disturbances (aphemia, then aphasia), progressing to complex partial phenomenology in the setting of frontal NCSE.

  3. Development of a novel rat mutant with spontaneous limbic-like seizures.

    PubMed Central

    Amano, S.; Ihara, N.; Uemura, S.; Yokoyama, M.; Ikeda, M.; Serikawa, T.; Sasahara, M.; Kataoka, H.; Hayase, Y.; Hazama, F.

    1996-01-01

    A new epileptic rat mutant with spontaneous seizures was developed by successive mating and selection from an inherited cataract rat. The procedures for developing the mutant and the symptomatology, electroencephalographic correlates, and neuropathology of the mutant are reported. It is possible that this rat stain will provide a useful animal model for human temporal lobe epilepsy. The seizures of the rat usually begin with face and head myoclonus, followed by rearing, and generalized clonic and tonic convulsions, all of which are symptomatologically the same as limbic seizures. Electrographic recording during generalized convulsive seizures demonstrated that sustained spike discharges emerged at the hippocampus and then propagated to the neocortex. Seizures occurred spontaneously without any artificial stimuli. Furthermore, external stimuli such as auditory, flashing light, or vestibular stimulations could not elicit epileptic attacks. Almost all of the male animals had generalized convulsions, mostly from 5 months after birth, and the frequency of the seizures increased with aging. Generalized convulsions developed in approximately 20% of the female rats. Microdysgenesis, such as abnormal neuronal clustering, neuronal disarrangement, or interruption of pyramidal neurons in the hippocampal formation, was found in the young rats that had not yet had generalized seizures. This microdysgenesis, which is though to be genetically programmed, was very interesting from the aspect of the relationship between structural abnormalities and epileptogenesis in this mutant. In addition to microdysgenesis, there was sprouting of mossy fibers into the inner molecular layer of the dentate gyrus in those adult rats that had repeated generalized convulsions. An increase of glial-fibrillary-acidic-protein-positive astrocytes with thickened and numerous processes, ie, astrogliosis, was also found in the cerebral cortex, amygdala region, and hippocampus of these adult animals. Judging

  4. Abnormal discharges from the temporal neocortex after selective amygdalohippocampectomy and seizure outcomes.

    PubMed

    Uda, Takehiro; Morino, Michiharu; Minami, Noriaki; Matsumoto, Takahiro; Uchida, Tatsuya; Kamei, Takamasa

    2015-11-01

    The present study examined the relationship between residual discharges from the temporal neocortex postoperatively and seizure outcomes, in mesial temporal lobe epilepsy (MTLE) patients with hippocampal sclerosis (HS) who were treated with selective amygdalohippocampectomy (SelAH). Abnormal discharges from the temporal neocortex are often observed and remain postoperatively. However, no recommendations have been made regarding whether additional procedures to eliminate these discharges should be performed for seizure relief. We retrospectively analyzed 28 patients with unilateral MTLE and HS, who underwent transsylvian SelAH. The mean follow-up period was 29 months (range: 16-49). In the pre- and postresection states, electrocorticography (ECoG) was recorded for the temporal base and lateral temporal cortex. The extent of resection was not influenced by the results of the preresection ECoG. Even if residual abnormal discharges were identified on the temporal neocortex, no additional procedures were undertaken to eliminate these abnormalities. The postresection spike counts were examined to determine the postresective alterations in spike count, and the frequency of residual spike count. The seizure outcomes were evaluated in all patients using the Engel classification. The postoperative seizure-free rate was 92.9%. No significant correlations were seen between a decreasing spike count and seizure outcomes (p=0.9259), or between the absence of residual spikes and seizure outcomes (p=1.000). Residual spikes at the temporal neocortex do not appear to influence seizure outcomes. Only mesial temporal structures should be removed, and additional procedures to eliminate residual spikes are not required.

  5. Search and Seizure in Schools.

    ERIC Educational Resources Information Center

    Hickok, Angelia B.

    1980-01-01

    Although problems of drug abuse, bomb threats, theft, and concealed weapons sometimes make search and seizure necessary, the student's rights must be protected through proper legal procedures. The article presents guidelines for conducting locker and personal searches and for educating students, teachers, and administrators on student rights. (DS)

  6. Virtual Cortical Resection Reveals Push-Pull Network Control Preceding Seizure Evolution.

    PubMed

    Khambhati, Ankit N; Davis, Kathryn A; Lucas, Timothy H; Litt, Brian; Bassett, Danielle S

    2016-09-07

    In ∼20 million people with drug-resistant epilepsy, focal seizures originating in dysfunctional brain networks will often evolve and spread to surrounding tissue, disrupting function in otherwise normal brain regions. To identify network control mechanisms that regulate seizure spread, we developed a novel tool for pinpointing brain regions that facilitate synchronization in the epileptic network. Our method measures the impact of virtually resecting putative control regions on synchronization in a validated model of the human epileptic network. By applying our technique to time-varying functional networks, we identified brain regions whose topological role is to synchronize or desynchronize the epileptic network. Our results suggest that greater antagonistic push-pull interaction between synchronizing and desynchronizing brain regions better constrains seizure spread. These methods, while applied here to epilepsy, are generalizable to other brain networks and have wide applicability in isolating and mapping functional drivers of brain dynamics in health and disease.

  7. Tonicity-responsive enhancer binding protein haplodeficiency attenuates seizure severity and NF-κB-mediated neuroinflammation in kainic acid-induced seizures

    PubMed Central

    Shin, H J; Kim, H; Heo, R W; Kim, H J; Choi, W S; Kwon, H M; Roh, G S

    2014-01-01

    Kainic acid (KA)-induced seizures followed by neuronal death are associated with neuroinflammation and blood–brain barrier (BBB) leakage. Tonicity-responsive enhancer binding protein (TonEBP) is known as a transcriptional factor activating osmoprotective genes, and in brain, it is expressed in neuronal nuclei. Thus dysregulation of TonEBP may be involved in the pathology of KA-induced seizures. Here we used TonEBP heterozygote (+/−) mice to study the roles of TonEBP. Electroencephalographic study showed that TonEBP (+/−) mice reduced seizure frequency and severity compared with wild type during KA-induced status epilepticus. Immunohistochemistry and western blotting analysis showed that KA-induced neuroinflammation and BBB leakage were dramatically reduced in TonEBP (+/−) mice. Similarly, TonEBP-specific siRNA reduced glutamate-induced death in HT22 hippocampal neuronal cells. TonEBP haplodeficiency prevented KA-induced nuclear translocation of NF-κB p65 and attenuated inflammation. Our findings identify TonEBP as a critical regulator of neuroinflammation and BBB leakage in KA-induced seizures, which suggests TonEBP as a good therapeutic target. PMID:24608792

  8. Extensive focal epithelial hyperplasia.

    PubMed

    Hashemipour, Maryam Alsadat; Shoryabi, Ali; Adhami, Shahrzad; Mehrabizadeh Honarmand, Hoda

    2010-01-01

    Heck's disease or focal epithelial hyperplasia is a benign contagious disease caused by human papillomavirus types 13 or 32. It occurs with low frequency in the Iranian population. This condition is characterized by the occurrence of multiple, small papules or nodules in the oral cavity, especially on the labial and buccal mucosa and tongue. In some populations, up to 39% of children are affected. Conservative surgical excision of lesions may be performed for diagnostic or aesthetic purposes. The risk of recurrence after this therapy is minimal, and there seems to be no malignant transformation potential. In the present work, we presented the clinical case of a 12-year-old Iranian girl with oral lesions that clinically and histologically correspond to Heck's disease.

  9. ACTH and prednisone in childhood seizure disorders.

    PubMed

    Snead, O C; Benton, J W; Myers, G J

    1983-08-01

    We treated 116 children with ACTH or prednisone. Fifty-two had infantile spasms with hypsarhythmia, and 64 had other types of intractable seizures. ACTH completely controlled seizures in all patients with infantile spasms and hypsarhythmia and 74% of those with other types of seizures. Prednisone controlled 51% of patients with infantile spasms and none with other seizures. Serious side effects were minimal for both drugs, and recurrent seizures occurred in 40 to 50% of patients within 4 to 14 months after completion of therapy.

  10. Evaluating the role of astrocytes on β-estradiol effect on seizures of Pilocarpine epileptic model.

    PubMed

    Sarfi, Masoumeh; Elahdadi Salmani, Mahmoud; Goudarzi, Iran; Lashkar Boluki, Taghi; Abrari, Kataneh

    2017-02-15

    Epilepsy with periodic and unpredictable seizures is associated with hippocampal glutamate toxicity and tissue reorganization. Astrocytes play an important role in mediating the neuroprotective effects of estradiol and reducing seizure severity. Accordingly, the protective effects of low and high doses of estradiol on behavioral, astrocytic involvement and neuronal survival aspects of Pilocarpine-induced epilepsy were investigated. Lithium- Pilocarpine (30mg/kg) model was used to provoke epilepsy. Βeta-estradiol (2,40μg/µl) was injected subcutaneously from 48 before to 48h after seizure induction. Behavioral convulsions were then monitored and recorded on the day of induction. Four weeks later, glutamine synthetase (GS) activity and the astrocyte transporter GLT-1 expression of the hippocampus were measured. Moreover, hippocampal glutamate and GABA were evaluated to study excitability changes. Finally, neuronal counting in the hippocampus was also performed using Nissl staining. The latency for generalized clonic (GC) convulsions significantly increased while the rate of GC and death significantly reduced due to β-estradiol treatment. GS activity and GLT-1 expression increased in the groups receiving the high dose of β-estradiol and Pilocarpine. Furthermore, the amount of both GABA and glutamate content decreased due to high dose of estradiol, while only GABA increased in Pilocarpine treated rats. Finally, administration of β-estradiol with low and high doses increased and improved the density of nerve cells. It is concluded that chronic administration β-estradiol has anticonvulsant and neuroprotective properties which are plausibly linked to astrocytic activity.

  11. Interictal EEG discoordination in a rat seizure model.

    PubMed

    Neymotin, Samuel A; Lee, Heekyung; Fenton, André A; Lytton, William W

    2010-12-01

    Cognitive and psychiatric comorbidities are common and clinically important in medial temporal lobe epilepsy and are likely caused by ongoing abnormalities in brain activity. In addition, it is unclear how the dynamics of interictal brain activity in medial temporal lobe epilepsy contributes to the generation of seizures. To investigate these issues, the authors evaluated multisite interictal EEG from a perinatal excitotoxic, hippocampal lesion rat model of medial temporal lobe epilepsy. Sample entropy, an information theoretical measure, demonstrated decreased complexity at different time scales and across all channels in epileptic animals. However, higher-order multiarea measures showed evidence of increased variability in population correlation measures. This apparent paradox was resolved by noting that although the EEG from epileptic animals was overall more stereotyped, there were frequent periods where two or more brain areas "broke off" from ongoing brain activity in epileptic animals, producing decorrelations between areas. These decorrelations were particularly apparent across the midline, suggesting impairments of interhemispheric coordination, a form of interhemispheric diaschisis. Both the observed alterations could contribute to a reduction in brain functionality: an overall reduction in complexity and a failure of interhemispheric brain coordination, suggesting a breakdown in communication between hemispheres. The authors speculate that any tendency of areas to lose communication or break away from coordinated brain activity might predispose to seizures in these areas.

  12. High-frequency oscillations, extent of surgical resection, and surgical outcome in drug-resistant focal epilepsy

    PubMed Central

    Haegelen, Claire; Perucca, Piero; Châtillon, Claude-Edouard; Andrade-Valença, Luciana; Zelmann, Rina; Jacobs, Julia; Collins, D. Louis; Dubeau, François; Olivier, André; Gotman, Jean

    2013-01-01

    Summary Purpose Removal of areas generating high-frequency oscillations (HFOs) recorded from the intracerebral electroencephalography (iEEG) of patients with medically intractable epilepsy has been found to be correlated with improved surgical outcome. However, whether differences exist according to the type of epilepsy is largely unknown. We performed a comparative assessment of the impact of removing HFO-generating tissue on surgical outcome between temporal lobe epilepsy (TLE) and extratemporal lobe epilepsy (ETLE). We also assessed the relationship between the extent of surgical resection and surgical outcome. Methods We studied 30 patients with drug-resistant focal epilepsy, 21 with TLE and 9 with ETLE. Two thirds of the patients were included in a previous report and for these, clinical and imaging data were updated and follow-up was extended. All patients underwent iEEG investigations (500 Hz high-pass filter and 2,000 Hz sampling rate), surgical resection, and postoperative magnetic resonance imaging (MRI). HFOs (ripples, 80–250 Hz; fast ripples, >250 Hz) were identified visually on a 5–10 min interictal iEEG sample. HFO rates inside versus outside the seizure-onset zone (SOZ), in resected versus nonresected tissue, and their association with surgical outcome (ILAE classification) were assessed in the entire cohort, and in the TLE and ETLE subgroups. We also tested the correlation of resected brain hippocampal and amygdala volumes (as measured on postoperative MRIs) with surgical outcome. Key Findings HFO rates were significantly higher inside the SOZ than outside in the entire cohort and TLE subgroup, but not in the ETLE subgroup. In all groups, HFO rates did not differ significantly between resected and nonresected tissue. Surgical outcome was better when higher HFO rates were included in the surgical resection in the entire cohort and TLE subgroup, but not in the ETLE subgroup. Resected brain hippocampal and amygdala volumes were not correlated with

  13. Seizure control by decanoic acid through direct AMPA receptor inhibition

    PubMed Central

    Chang, Pishan; Augustin, Katrin; Boddum, Kim; Williams, Sophie; Sun, Min; Terschak, John A.; Hardege, Jörg D.; Chen, Philip E.

    2016-01-01

    See Rogawski (doi:10.1093/awv369) for a scientific commentary on this article.  The medium chain triglyceride ketogenic diet is an established treatment for drug-resistant epilepsy that increases plasma levels of decanoic acid and ketones. Recently, decanoic acid has been shown to provide seizure control in vivo, yet its mechanism of action remains unclear. Here we show that decanoic acid, but not the ketones β-hydroxybutryate or acetone, shows antiseizure activity in two acute ex vivo rat hippocampal slice models of epileptiform activity. To search for a mechanism of decanoic acid, we show it has a strong inhibitory effect on excitatory, but not inhibitory, neurotransmission in hippocampal slices. Using heterologous expression of excitatory ionotropic glutamate receptor AMPA subunits in Xenopus oocytes, we show that this effect is through direct AMPA receptor inhibition, a target shared by a recently introduced epilepsy treatment perampanel. Decanoic acid acts as a non-competitive antagonist at therapeutically relevant concentrations, in a voltage- and subunit-dependent manner, and this is sufficient to explain its antiseizure effects. This inhibitory effect is likely to be caused by binding to sites on the M3 helix of the AMPA-GluA2 transmembrane domain; independent from the binding site of perampanel. Together our results indicate that the direct inhibition of excitatory neurotransmission by decanoic acid in the brain contributes to the anti-convulsant effect of the medium chain triglyceride ketogenic diet. PMID:26608744

  14. Nonlinear analysis of EEG for epileptic seizures

    SciTech Connect

    Hively, L.M.; Clapp, N.E.; Daw, C.S.; Lawkins, W.F.; Eisenstadt, M.L.

    1995-04-01

    We apply chaotic time series analysis (CTSA) to human electroencephalogram (EEG) data. Three epoches were examined: epileptic seizure, non-seizure, and transition from non-seizure to seizure. The CTSA tools were applied to four forms of these data: raw EEG data (e-data), artifact data (f-data) via application of a quadratic zero-phase filter of the raw data, artifact-filtered data (g- data) and that was the residual after subtracting f-data from e-data, and a low-pass-filtered version (h-data) of g-data. Two different seizures were analyzed for the same patient. Several nonlinear measures uniquely indicate an epileptic seizure in both cases, including an abrupt decrease in the time per wave cycle in f-data, an abrupt increase in the Kolmogorov entropy and in the correlation dimension for e-h data, and an abrupt increase in the correlation dimension for e-h data. The transition from normal to seizure state also is characterized by distinctly different trends in the nonlinear measures for each seizure and may be potential seizure predictors for this patient. Surrogate analysis of e-data shows that statistically significant nonlinear structure is present during the non-seizure, transition , and seizure epoches.

  15. Inferring Seizure Frequency From Brief EEG Recordings

    PubMed Central

    Westover, M. Brandon; Bianchi, Matt T.; Shafi, Mouhsin; Hoch, Daniel B.; Cole, Andrew J.; Chiappa, Keith; Cash, Sydney S.

    2012-01-01

    Routine EEGs remain a cornerstone test in caring for people with epilepsy. Although rare, a self-limited seizure (clinical or electrographic only) may be observed during such brief EEGs. The implications of observing a seizure in this situation, especially with respect to inferring the underlying seizure frequency, are unclear. The issue is complicated by the inaccuracy of patient-reported estimations of seizure frequency. The treating clinician is often left to wonder whether the single seizure indicates very frequent seizures, or if it is of lesser significance. We applied standard concepts of probabilistic inference to a simple model of seizure incidence to provide some guidance for clinicians facing this situation. Our analysis establishes upper and lower bounds on the seizure rate implied by observing a single seizure during routine EEG. Not surprisingly, with additional information regarding the expected seizure rate, these bounds can be further constrained. This framework should aid the clinician in applying a more principled approach toward decision making in the setting of a single seizure on a routine EEG. PMID:23545768

  16. Inferring seizure frequency from brief EEG recordings.

    PubMed

    Westover, M Brandon; Bianchi, Matt T; Shafi, Mouhsin; Hoch, Daniel B; Cole, Andrew J; Chiappa, Keith; Cash, Sydney S

    2013-04-01

    Routine EEGs remain a cornerstone test in caring for people with epilepsy. Although rare, a self-limited seizure (clinical or electrographic only) may be observed during such brief EEGs. The implications of observing a seizure in this situation, especially with respect to inferring the underlying seizure frequency, are unclear. The issue is complicated by the inaccuracy of patient-reported estimations of seizure frequency. The treating clinician is often left to wonder whether the single seizure indicates very frequent seizures, or if it is of lesser significance. We applied standard concepts of probabilistic inference to a simple model of seizure incidence to provide some guidance for clinicians facing this situation. Our analysis establishes upper and lower bounds on the seizure rate implied by observing a single seizure during routine EEG. Not surprisingly, with additional information regarding the expected seizure rate, these bounds can be further constrained. This framework should aid the clinician in applying a more principled approach toward decision making in the setting of a single seizure on a routine EEG.

  17. [Case report of muscle cramp versus focal epilepsy].

    PubMed

    Fujita, H; Muranaka, H; Osari, S; Kimura, Y; Goto, A; Koda, M; Shiotani, M; Ozaki, I

    1999-09-01

    We report here a boy suffering from muscle cramps in the right upper extremity. At 32 days of age, he developed purulent meningitis followed by paresis of the right upper extremity. From infancy he had intermittent episodes myoclonus-like involving the right hand. Since he also had true epileptic seizures with loss of consciousness, ocular deviation, and vomiting at 6 and 8 years of age, he was treated with anti-epileptic drugs as therapy for focal motor seizures. At 6 years of age, these episodes increased in frequency. The cramps spread from the right hand to involve the entire upper extremity with pain. At the age of 10, he was referred to Hirosaki University Hospital and was admitted. Using closed circuit television with continuous EEG and EMG monitoring we observed during his episodes repeated EMG abnormalities consisting of continuous discharges of polyphasic motor unit potentials, but no epileptic EEG discharges. We diagnosed these episodes as muscle cramp. His muscle cramps were controlled by medication with muscle relaxants and Chinese medicines. This case illustrates that the differential diagnosis between muscle cramps and epileptic seizures is important for proper treatment.

  18. Gelastic seizures involving the right parietal lobe.

    PubMed

    Shin, Hee-Young; Hong, Seung Bong; Joo, Eun Yeon; Tae, Woo Suk; Han, Sun Jung; Cho, Jae Wook; Seo, Dae Won; Kim, Sun Hyung; Lee, Jong-Min; Kim, Sun I

    2006-09-01

    Gelastic seizures have been described in various epilepsies arising from the temporal or frontal lobes, although the most commonly encountered form is related to the presence of an hypothalamic hamartoma. We report a patient with gelastic seizures involving the right parietal lobe. Our patient, a 32-year-old man, underwent video-EEG monitoring, interictal and ictal brain SPECTs during gelastic seizures. Subtraction ictal SPECT co-registered to MRI (SISCOM), was performed to localize any ictal hyperperfusion during these gelastic seizures. The seizures consisted of brief staring followed by smiling and laughing. Electroencephalography during the gelastic seizures showed rhythmic sharp waves in the right parietal lobe. SISCOM showed ictal hyperperfusion in the right parietal lobe and medial portions of right cerebellum. Our findings suggest that the right parietal lobe may actively participate in the particular epileptogenic network generating gelastic seizures.

  19. Electromyogram-evoked focal myositis

    PubMed Central

    Snipes, George; Quan, Carolyn

    2017-01-01

    Focal myositis is a rarely reported inflammatory disease of skeletal muscle, particularly of an extremity. It is often misinterpreted as an infectious syndrome, leading to prolonged antibiotic use and a delay in immunosuppressive therapy. Without a confirmed etiology to date, we present a case of recurrent focal myositis following an electromyogram. PMID:28127151

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  3. Effects of selective neonatal hippocampal lesions on tests of object and spatial recognition memory in monkeys

    PubMed Central

    Heuer, Eric; Bachevalier, Jocelyne

    2011-01-01

    Earlier studies in monkeys have reported mild impairment in recognition memory following nonselective neonatal hippocampal lesions (Bachevalier, Beauregard, & Alvarado, 1999; Rehbein, Killiany, & Mahut, 2005). To assess whether the memory impairment could have resulted from damage to cortical areas adjacent to the hippocampus, we tested adult monkeys with neonatal focal hippocampal lesions and sham-operated controls in three recognition tasks: delayed nonmatching-to-sample, object memory span, and spatial memory span. Further, to rule out that normal performance on these tasks may relate to functional sparing following neonatal hippocampal lesions, we tested adult monkeys that had received the same focal hippocampal lesions in adulthood and their controls in the same three memory tasks. Both early and late onset focal hippocampal damage did not alter performance on any of the three tasks, suggesting that damage to cortical areas adjacent to the hippocampus was likely responsible for the recognition impairment reported by the earlier studies. In addition, given that animals with early and late onset hippocampal lesions showed object and spatial recognition impairment when tested in a visual paired comparison task (Zeamer, Meunier, & Bachevalier, Submitted; Zeamer, Heuer & Bachevalier, 2010), the data suggest that not all object and spatial recognition tasks are solved by hippocampal-dependent memory processes. The current data may not only help explain the neural substrate for the partial recognition memory impairment reported in cases of developmental amnesia (Adlam, Malloy, Mishkin, & Vargha-Khadem, 2009), but they are also clinically relevant given that the object and spatial memory tasks used in monkeys are often translated to investigate memory functions in several populations of human infants and children in which dysfunction of the hippocampus is suspected. PMID:21341885

  4. Seizure-induced disinhibition of the HPA axis increases seizure susceptibility.

    PubMed

    O'Toole, Kate K; Hooper, Andrew; Wakefield, Seth; Maguire, Jamie

    2014-01-01

    Stress is the most commonly reported precipitating factor for seizures. The proconvulsant actions of stress hormones are thought to mediate the effects of stress on seizure susceptibility. Interestingly, epileptic patients have increased basal levels of stress hormones, including corticotropin-releasing hormone (CRH) and corticosterone, which are further increased following seizures. Given the proconvulsant actions of stress hormones, we proposed that seizure-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis may contribute to future seizure susceptibility. Consistent with this hypothesis, our data demonstrate that pharmacological induction of seizures in mice with kainic acid or pilocarpine increases circulating levels of the stress hormone, corticosterone, and exogenous corticosterone administration is sufficient to increase seizure susceptibility. However, the mechanism(s) whereby seizures activate the HPA axis remain unknown. Here we demonstrate that seizure-induced activation of the HPA axis involves compromised GABAergic control of CRH neurons, which govern HPA axis function. Following seizure activity, there is a collapse of the chloride gradient due to changes in NKCC1 and KCC2 expression, resulting in reduced amplitude of sIPSPs and even depolarizing effects of GABA on CRH neurons. Seizure-induced activation of the HPA axis results in future seizure susceptibility which can be blocked by treatment with an NKCC1 inhibitor, bumetanide, or blocking the CRH signaling with Antalarmin. These data suggest that compromised GABAergic control of CRH neurons following an initial seizure event may cause hyperexcitability of the HPA axis and increase future seizure susceptibility.

  5. Culturing rat hippocampal neurons.

    PubMed

    Audesirk, G; Audesirk, T; Ferguson, C

    2001-01-01

    Cultured neurons are widely used to investigate the mechanisms of neurotoxicity. Embryonic rat hippocampal neurons may be grown as described under a wide variety of conditions to suit differing experimental procedures, including electrophysiology, morphological analysis of neurite development, and various biochemical and molecular analyses.

  6. Tardive seizure: a case report.

    PubMed

    Williams, Adedapo; Adetunji, Babatunde; Odulate, Adeola

    2006-12-01

    Electroconvulsive therapy remains the best option for treatment-resistant depressive episodes. A rare, but potentially dangerous, complication is tardive seizures, which occur after the patient has already stopped convulsing from the electroconvulsive therapy and has recovered full consciousness. We have decided to report this case, which many psychiatrists and psychiatry residents may not be familiar with, to heighten the awareness of the condition because it has ramifications in terms of safe management of the patients concerned.

  7. Focal cerebral mantle disruption in fetal hydrocephalus.

    PubMed

    Humphreys, Peter; Muzumdar, Dattatraya P; Sly, Lloyd E; Michaud, Jean

    2007-04-01

    A variety of developmental brain anomalies have been described in individuals with fetal hydrocephalus, regardless of etiology. Examples include callosal dysgenesis, periventricular gray matter heterotopia, hippocampal and white matter hypoplasia, and cortical polygyration. The present report draws attention to another anomaly not reported in previous case series of fetal hydrocephalus: focal cerebral mantle disruption. Neonatal imaging findings (where available) and post-shunt, stable-state magnetic resonance imaging, or pathological findings were reviewed in 77 subjects with fetal hydrocephalus (55 myelomeningocele, 16 sporadic aqueductal stenosis, 6 miscellaneous). Of these, 12 subjects (15.6%) demonstrated a combination of absence of the septum pellucidum and severe thinning or absence of the posteromesial cerebral mantle. On axial sequences, this combination created the illusion of a common ventricle, as in lobar holoprosencephaly. All 12 subjects had massive hydrocephalus at birth, accompanied in 7 by posteromesial ventricular diverticula. Two subjects, and one other subject with distinct lateral ventricles, demonstrated unilateral or bilateral mantle clefts suggestive of schizencephaly. Close radiological (n = 2) or pathological (n = 1) inspection showed that the clefts were only partially lined with gray matter and contained a transverse gliotic membrane. These findings are consistent with the hypothesis that massive early fetal hydrocephalus may completely disrupt cerebral mantle formation, particularly in the posteromesial hemispheres.

  8. Prevalence, Response to Cysticidal Therapy, and Risk Factors for Persistent Seizure in Indian Children with Neurocysticercosis

    PubMed Central

    Kumar, Animesh; Mandal, Anirban; Sinha, Sheela; Singh, Amitabh

    2017-01-01

    Background. Neurocysticercosis (NCC) is the commonest cause of childhood acquired epilepsy in developing countries. The use of cysticidal therapy in NCC, except “single lesion NCC,” is still debated in view of its doubtful usefulness and potential adverse effects. Methods. Children presenting with first episode of seizure or acute focal neurological deficit without fever were screened for NCC and received appropriate therapy (followup done for 1 year to look for the response and side effects). Results. The prevalence of NCC was 4.5%. Most common presenting feature was generalized seizure and commonest imaging finding was single small enhancing lesion in the parietal lobe. Abnormal EEG and CSF abnormalities were found in almost half of the children. The response to therapy was very good with infrequent recurrence of seizure and adverse effects of therapy were encountered rarely. No risk factors for persistent seizure could be identified. Conclusion. Present study shows that the response to cysticidal therapy is very good in NCC as seizure recurrence was observed in only 5%, 4.2%, and 4.2% of cases at 3-month, 6-month, and 1-year followup. Adverse effects of therapy were observed in 20% of cases during therapy but they were mild and self-limiting. PMID:28167968

  9. Early presentation of de novo high grade glioma with epileptic seizures: electroclinical and neuroimaging findings.

    PubMed

    Rossi, Rosario; Figus, Andrea; Corraine, Simona

    2010-10-01

    We report the clinical, EEG and neuroradiologic findings from three adult patients who developed new-onset seizure disorders as early clinical manifestations of de novo high grade glioma. The malignancies could not be recognised at the time of the first epileptic seizure because of minimal non-specific brain abnormalities, which showed no signs of necrosis or significant contrast enhancement on computed tomography and magnetic resonance imaging. Focal EEG abnormalities were recorded in all cases and appeared consistent with the neuroradiologic findings. The patients regained normal neurological status after the first seizure but rapidly developed space-occupying necrotic lesions. Two patients underwent surgery and received histological diagnoses of the tumours. Another patient was finally diagnosed with a malignant glioma based on the neuroradiologic picture and rapid progression of the cerebral lesion. It should be noted that in adult patients, new-onset epileptic seizures might reveal the presence of malignant gliomas at a very early stage in the tumour formation process. This report indicates that typical anatomoradiologic features of de novo high grade glioma, such as necrosis and rim-contrast enhancement, could be absent at the time of the first epileptic seizure but become clear within a short period after clinical presentation.

  10. Smartphone applications for seizure management.

    PubMed

    Pandher, Puneet Singh; Bhullar, Karamdeep Kaur

    2016-06-01

    Technological advancements continue to provide innovative ways of enhancing patient care in medicine. In particular, the growing popularity of smartphone technology has seen the recent emergence of a myriad of healthcare applications (or apps) that promise to help shape the way in which health information is delivered to people worldwide. While limited research already exists on a range of such apps, our study is the first to examine the salient features of smartphone applications as they apply to the area of seizure management. For the purposes of this review, we conducted a search of the official online application stores of the five major smartphone platforms: iPhone, Android, Blackberry, Windows Mobile and Nokia-Symbian. Apps were included if they reported to contain some information or tools relating to seizure management and excluded if they were aimed exclusively at health professionals. A total of 28 applications met these criteria. Overall, we found an increasing number of epilepsy apps available on the smartphone market, but with only a minority offering comprehensive educational information alongside tools such as seizure diaries, medication tracking and/or video recording.

  11. Persistent changes in action potential broadening and the slow afterhyperpolarization in rat CA1 pyramidal cells after febrile seizures.

    PubMed

    Kamal, Amer; Notenboom, Robbert G E; de Graan, Pierre N E; Ramakers, Geert M J

    2006-04-01

    Febrile (fever-induced) seizures (FS) are the most common form of seizures during childhood and have been associated with an increased risk of epilepsy later in life. The relationship of FS to subsequent epilepsy is, however, still controversial. Insights from animal models do indicate that especially complex FS are harmful to the developing brain and contribute to a hyperexcitable state that may persist for life. Here, we determined long-lasting changes in neuronal excitability of rat hippocampal CA1 pyramidal cells after prolonged (complex) FS induced by hyperthermia on postnatal day 10. We show that hyperthermia-induced seizures at postnatal day 10 induce a long-lasting increase in the hyperpolarization-activated current I(h). Furthermore, we show that a reduction in the amount of spike broadening and in the amplitude of the slow afterhyperpolarization following FS are also likely to contribute to the hyperexcitability of the hippocampus long term.

  12. The expression of kainate receptor subunits in hippocampal astrocytes after experimentally induced status epilepticus.

    PubMed

    Vargas, Jay R; Takahashi, D Koji; Thomson, Kyle E; Wilcox, Karen S

    2013-10-01

    Astrocytes have emerged as active participants of synaptic transmission and are increasingly implicated in neurologic disorders including epilepsy. Adult glial fibrillary acidic protein (GFAP)-positive hippocampal astrocytes are not known for ionotropic glutamate receptor expression under basal conditions. Using a chemoconvulsive status epilepticus (SE) model of temporal lobe epilepsy, we show by immunohistochemistry and colocalization analysis that reactive hippocampal astrocytes express kainate receptor (KAR) subunits after SE. In the CA1 region, GluK1, GluK2/3, GluK4, and GluK5 subunit expression was observed in GFAP-positive astrocytes during the seizure-free or "latent" period 1 week after SE. At 8 weeks after SE, a time after SE when spontaneous behavioral seizures occur, the GluK1 and GluK5 subunits remained expressed at significant levels. Kainate receptor subunit expression was found in astrocytes in the hippocampus and surrounding cortex but not in GFAP-positive astrocytes of striatum, olfactory bulb, or brainstem. To examine hippocampal KAR expression more broadly, astroglial-enriched tissue fractions were prepared from dissected hippocampi and were found to have greater GluK4 expression after SE than controls. These results demonstrate that astrocytes begin to express KARs after seizure activity and suggest that their expression may contribute to the pathophysiology of epilepsy.

  13. Seizure related accidents and injuries in childhood.

    PubMed

    Buffo, Thais Helena; Guerreiro, Marilisa M; Tai, Peter; Montenegro, Maria Augusta

    2008-09-01

    Several studies show that the risk of accidents involving patients with epilepsy is much higher compared to the general population. The objective of this study was to identify the frequency and type of seizure related injuries in children diagnosed with epilepsy. In addition we also assessed possible risk factors associated with this seizure related accidents in childhood. This study was conducted at the pediatric epilepsy clinic of Unicamp, from January 2005 to August 2006. We evaluated 100 consecutive children with epilepsy. Parents were interviewed by one of the authors using a structured questionnaire that included questions about seizure related accidents and related injuries. Forty-four patients reported seizure related accidents. Eighteen patients needed medical assistance at an emergency room due the severity of their seizure related accident. Forty patients reported having a seizure related accident prevented by a bystander. Another 14 patients reported avoiding a seizure related accident by luck alone. Contusions and lacerations were the most common type of lesion associated with seizures. Patients with symptomatic/probable symptomatic epilepsy and those using higher numbers of anti-epileptic drugs (AEDs) were at greater risk for seizure related accidents (p<0.05). We conclude that patients with symptomatic/probable symptomatic epilepsy and on multiple AEDs are at increased risk of seizure related accidents. Parents and caretakers should be even more cautious about risk of injury in such patients.

  14. Ictal Asystole in Focal Epilepsy

    PubMed Central

    Sarwal, Aarti

    2015-01-01

    Ictal bradyarrhythmias are rare episodes occurring in patients with or without a past cardiac history. These episodes go unnoticed unless the patient is monitored on simultaneous video-electroencephalogram and 1-lead electrocardiogram. Recognizing ictal bradyarrhythmias is important, since episodes may predispose patients to sudden, unexplained death in epilepsy. We present 2 cases of ictal asystole in patients with right temporal lobe epilepsy. The first patient had seizures refractory to medical therapy and received a pacemaker. The seizures in the second patient responded well to antiepileptic medication, and a pacemaker was deferred. These cases highlight the differing cardiovascular treatment options for ictal asystole. PMID:26425256

  15. Two-year seizure reduction in adults with medically intractable partial onset epilepsy treated with responsive neurostimulation: Final results of the RNS System Pivotal trial

    PubMed Central

    Heck, Christianne N; King-Stephens, David; Massey, Andrew D; Nair, Dileep R; Jobst, Barbara C; Barkley, Gregory L; Salanova, Vicenta; Cole, Andrew J; Smith, Michael C; Gwinn, Ryder P; Skidmore, Christopher; Van Ness, Paul C; Bergey, Gregory K; Park, Yong D; Miller, Ian; Geller, Eric; Rutecki, Paul A; Zimmerman, Richard; Spencer, David C; Goldman, Alica; Edwards, Jonathan C; Leiphart, James W; Wharen, Robert E; Fessler, James; Fountain, Nathan B; Worrell, Gregory A; Gross, Robert E; Eisenschenk, Stephan; Duckrow, Robert B; Hirsch, Lawrence J; Bazil, Carl; O'Donovan, Cormac A; Sun, Felice T; Courtney, Tracy A; Seale, Cairn G; Morrell, Martha J

    2014-01-01

    Objective To demonstrate the safety and effectiveness of responsive stimulation at the seizure focus as an adjunctive therapy to reduce the frequency of seizures in adults with medically intractable partial onset seizures arising from one or two seizure foci. Methods Randomized multicenter double-blinded controlled trial of responsive focal cortical stimulation (RNS System). Subjects with medically intractable partial onset seizures from one or two foci were implanted, and 1 month postimplant were randomized 1:1 to active or sham stimulation. After the fifth postimplant month, all subjects received responsive stimulation in an open label period (OLP) to complete 2 years of postimplant follow-up. Results All 191 subjects were randomized. The percent change in seizures at the end of the blinded period was −37.9% in the active and −17.3% in the sham stimulation group (p = 0.012, Generalized Estimating Equations). The median percent reduction in seizures in the OLP was 44% at 1 year and 53% at 2 years, which represents a progressive and significant improvement with time (p < 0.0001). The serious adverse event rate was not different between subjects receiving active and sham stimulation. Adverse events were consistent with the known risks of an implanted medical device, seizures, and of other epilepsy treatments. There were no adverse effects on neuropsychological function or mood. Significance Responsive stimulation to the seizure focus reduced the frequency of partial-onset seizures acutely, showed improving seizure reduction over time, was well tolerated, and was acceptably safe. The RNS System provides an additional treatment option for patients with medically intractable partial-onset seizures. PMID:24621228

  16. Parvalbumin-Positive Inhibitory Interneurons Oppose Propagation But Favor Generation of Focal Epileptiform Activity.

    PubMed

    Sessolo, Michele; Marcon, Iacopo; Bovetti, Serena; Losi, Gabriele; Cammarota, Mario; Ratto, Gian Michele; Fellin, Tommaso; Carmignoto, Giorgio

    2015-07-01

    Parvalbumin (Pv)-positive inhibitory interneurons effectively control network excitability, and their optogenetic activation has been reported to block epileptic seizures. An intense activity in GABAergic interneurons, including Pv interneurons, before seizures has been described in different experimental models of epilepsy, raising the hypothesis that an increased GABAergic inhibitory signal may, under certain conditions, initiate seizures. It is therefore unclear whether the activity of Pv interneurons enhances or opposes epileptiform activities. Here we use a mouse cortical slice model of focal epilepsy in which the epileptogenic focus can be identified and the role of Pv interneurons in the generation and propagation of seizure-like ictal events is accurately analyzed by a combination of optogenetic, electrophysiological, and imaging techniques. We found that a selective activation of Pv interneurons at the focus failed to block ictal generation and induced postinhibitory rebound spiking in pyramidal neurons, enhancing neuronal synchrony and promoting ictal generation. In contrast, a selective activation of Pv interneurons distant from the focus blocked ictal propagation and shortened ictal duration at the focus. We revealed that the reduced ictal duration was a direct consequence of the ictal propagation block, probably by preventing newly generated afterdischarges to travel backwards to the original focus of ictal initiation. Similar results were obtained upon individual Pv interneuron activation by intracellular depolarizing current pulses. The functional dichotomy of Pv interneurons here described opens new perspectives to our understanding of how local inhibitory circuits govern generation and spread of focal epileptiform activities.

  17. Focal and secondarily generalised convulsive status epilepticus induced by thiocolchicoside in the rat.

    PubMed

    Sechi, GianPietro; De Riu, Pierluigi; Mameli, Ombretta; Deiana, Giovanni A; Cocco, Giovanni A; Rosati, Giulio

    2003-10-01

    The objective of this study was to document the convulsant properties of thiocolchicoside in rats, and to characterise the electroclinical pattern of epileptic seizures. Experiments were carried out in three groups of male Wistar rats: in group A, thiocolchicoside was applied topically to the pia, or given by microinjection to the cerebral cortex (2 microg/microl); in group B, the drug was administered parenterally (6 mg/kg) to rats with minimal lesions of the dura and arachnoid membranes; in group C, thiocolchicoside was administered parenterally (up to 12 mg/kg) to intact rats. In all animals, electroclinical activity was continuously monitored for at least 3 hours after thiocolchicoside injection or application. In group A, electrographic and behavioural activity of focal motor seizures occurred in 100% of animals, developing into a focal status epilepticus; in group B, a multifocal epileptic pattern with secondary generalisation, clinically characterised by clonic or tonic-clonic seizures occurred in 100% of animals, until a secondarily generalised convulsive status epilepticus; in group C, none of animals showed either electrographic or behavioural seizure activity. Our study documents that thiocolchicoside has a powerful convulsant activity in the rat, perhaps due to an antagonistic interaction of the compound with a cortical subtype of the GABA(A) receptor.

  18. Novel Vitamin K analogs suppress seizures in zebrafish and mouse models of epilepsy.

    PubMed

    Rahn, J J; Bestman, J E; Josey, B J; Inks, E S; Stackley, K D; Rogers, C E; Chou, C J; Chan, S S L

    2014-02-14

    Epilepsy is a debilitating disease affecting 1-2% of the world's population. Despite this high prevalence, 30% of patients suffering from epilepsy are not successfully managed by current medication suggesting a critical need for new anti-epileptic drugs (AEDs). In an effort to discover new therapeutics for the management of epilepsy, we began our study by screening drugs that, like some currently used AEDs, inhibit histone deacetylases (HDACs) using a well-established larval zebrafish model. In this model, 7-day post fertilization (dpf) larvae are treated with the widely used seizure-inducing compound pentylenetetrazol (PTZ) which stimulates a rapid increase in swimming behavior previously determined to be a measurable manifestation of seizures. In our first screen, we tested a number of different HDAC inhibitors and found that one, 2-benzamido-1 4-naphthoquinone (NQN1), significantly decreased swim activity to levels equal to that of valproic acid, 2-n-propylpentanoic acid (VPA). We continued to screen structurally related compounds including Vitamin K3 (VK3) and a number of novel Vitamin K (VK) analogs. We found that VK3 was a robust inhibitor of the PTZ-induced swim activity, as were several of our novel compounds. Three of these compounds were subsequently tested on mouse seizure models at the National Institute of Neurological Disorders and Stroke (NINDS) Anticonvulsant Screening Program. Compound 2h reduced seizures particularly well in the minimal clonic seizure (6Hz) and corneal-kindled mouse models of epilepsy, with no observable toxicity. As VK3 affects mitochondrial function, we tested the effects of our compounds on mitochondrial respiration and ATP production in a mouse hippocampal cell line. We demonstrate that these compounds affect ATP metabolism and increase total cellular ATP. Our data indicate the potential utility of these and other VK analogs for the prevention of seizures and suggest the potential mechanism for this protection may lie in the

  19. Novel Vitamin K analogues suppress seizures in zebrafish and mouse models of epilepsy

    PubMed Central

    Rahn, Jennifer J.; Bestman, Jennifer E.; Josey, Benjamin J.; Inks, Elizabeth S.; Stackley, Krista D.; Rogers, Carolyn E.; Chou, C. James; Chan, Sherine S. L.

    2014-01-01

    Epilepsy is a debilitating disease affecting 1-2% of the world’s population. Despite this high prevalence, 30% of patients suffering from epilepsy are not successfully managed by current medication suggesting a critical need for new anti-epileptic drugs (AEDs). In an effort to discover new therapeutics for the management of epilepsy, we began our study by screening drugs that, like some currently used AEDs, inhibit HDACs using a well-established larval zebrafish model. In this model, 7-day post fertilization (dpf) larvae are treated with the widely used seizure-inducing compound pentylenetetrazol (PTZ) which stimulates a rapid increase in swimming behavior previously determined to be a measurable manifestation of seizures. In our first screen, we tested a number of different HDAC inhibitors and found that one, NQN1, significantly decreased swim activity to levels equal to that of VPA. We continued to screen structurally related compounds including Vitamin K3 (VK3) and a number of novel Vitamin K (VK) analogues. We found that VK3 was a robust inhibitor of the PTZ-induced swim activity, as were several of our novel compounds. Three of these compounds were subsequently tested on mouse seizure models at the National Institute of Neurological Disorders and Stroke (NINDS) Anticonvulsant Screening Program. Compound 2h reduced seizures particularly well in the minimal clonic seizure (6 Hz) and corneal kindled mouse models of epilepsy, with no observable toxicity. As VK3 affects mitochondrial function, we tested the effects of our compounds on mitochondrial respiration and ATP production in a mouse hippocampal cell line. We demonstrate that these compounds affect ATP metabolism and increase total cellular ATP. Our data indicate the potential utility of these and other VK analogues for prevention of seizures and suggest the potential mechanism for this protection may lie in the ability of these compounds to affect energy production. PMID:24291671

  20. The role for nitric oxide on the effects of hydroalcoholic extract of Achillea wilhelmsii on seizure

    PubMed Central

    Hosseini, Mahmoud; Harandizadeh, Fatemeh; Niazmand, Saeed; Soukhtanloo, Mohammad; Faizpour, Azadeh; Ghasemabady, Marzieh

    2014-01-01

    Objective : Nitric oxide (NO) plays an important role both as a consequence and as a cause of epileptic seizures. Regarding the central nervous system depressant effects of Achillea wilhelmsii (A. wilhelmsii), as well the effects of the plant on NO, this study was aimed to elucidate the possible role for nitric oxide on the effects of hydroalcoholic extract of A. wilhelmsii on pentylenetetrazole (PTZ)-induced seizures. Materials and Methods: Fifty-six male Wistar rats were divided into 7 groups (n=8 in each group) and treated with (1) normal saline, (2) normal saline before pentylenetetrazole (PTZ, 90 mg/kg), (3-7) A. wilhelmsii extract (100, 200, 400, 800, and 1200 mg/kg) before PTZ. Latency to first minimal colonic seizure (MCS) and the first generalized tonic-clonic seizures (GTCS) as well as the mortality rate were recorded. The brain tissues were then removed for biochemical measurements. Fisher’s exact probability test as well as analysis of variance (ANOVA), followed by Tukey’s test were used for statistical evaluation. Results: Treatment with 100- 1200 mg/kg of the extract did not affect MCS latencies. 400 mg/kg of the extract prolonged GTCS latency (p<0.001), however, the lower and higher doses were not effective. Nitric oxide metabolites concentrations in the hippocampal tissues of the animals treated with 100, 200, and 400 mg/kg of the extract were increased compared with saline (p<0.05-p<0.01). Conclusion: The present study showed that hydroalcoholic extract of A. wilhelmsii affects NO metabolites in brain tissues as well the severity of seizures in PTZ-induced seizure model. PMID:25068139

  1. Ketone Bodies Mediate Anti-Seizure Effects Through Mitochondrial Permeability Transition

    PubMed Central

    Kim, Do Young; Simeone, Kristina A.; Simeone, Timothy A.; Pandya, Jignesh D.; Wilke, Julianne C.; Ahn, Younghee; Geddes, James W.; Sullivan, Patrick G.; Rho, Jong M.

    2015-01-01

    Objective Ketone bodies (KB) are products of fatty acid oxidation and serve as essential fuels during fasting or treatment with the high-fat anti-seizure ketogenic diet (KD). Despite growing evidence that KB exert broad neuroprotective effects, their role in seizure control has not been firmly demonstrated. The major goal of this study was to demonstrate the direct anti-seizure effects of KB and to identify an underlying target mechanism. Methods We studied the effects of both the KD and KB in spontaneously epileptic Kcna1-null mice using a combination of behavioral, planar multi-electrode, and standard cellular electophysiological techniques. Thresholds for mitochondrial permeability transition (mPT) were determined in acutely isolated brain mitochondria. Results KB alone were sufficient to: (1) exert anti-seizure effects in Kcna1-null mice; (2) restore intrinsic impairment of hippocampal long-term potentiation (LTP) and spatial learning-memory defects in Kcna1-null mutants; and (3) raise the threshold for calcium-induced mPT in acutely prepared mitochondria from hippocampi of Kcna1-null animals. Targeted deletion of the cyclophilin D (CypD) subunit of the mPT complex abrogated the effects of KB on mPT, and in vivo pharmacological inhibition and activation of mPT were found to mirror and reverse, respectively, the anti-seizure effects of the KD in Kcna1-null mice. Interpretation The present data reveal the first direct link between mPT and seizure control, and provide a potential mechanistic explanation for the KD. Given that mPT is increasingly being implicated in diverse neurological disorders, our results suggest that metabolism-based treatments and/or metabolic substrates might represent a worthy paradigm for therapeutic development. PMID:25899847

  2. Morphological variations of hippocampal formation in epilepsy: image, clinical and electrophysiological data.

    PubMed

    Hamad, Ana Paula Andrade; Carrete, Henrique; Bianchin, Marino Muxfeldt; Ferrari-Marinho, Taissa; Lin, Katia; Yacubian, Elza Márcia Targas; Vilanova, Luiz Celso Pereira; Garzon, Eliana; Caboclo, Luís Otávio; Sakamoto, Américo Ceiki

    2013-01-01

    Morphological variations of hippocampal formation (MVHF) are observed in patients with epilepsy but also in asymptomatic individuals. The precise role of these findings in epilepsy is not yet fully understood. This study analyzes the hippocampal formation (HF) morphology of asymptomatic individuals (n = 30) and of patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS) (n = 68), patients with malformations of cortical development (MCD) (n = 34), or patients with pure morphological variations of hippocampal formation (pure MVHF) (n = 12). Main clinical and electrophysiological data of patients with MVHF were also analyzed. Morphological variations of hippocampal formation are more frequently observed in patients with MCD than in patients with MTLE-HS or in asymptomatic individuals. Patients with pure morphological variations of hippocampal formation showed higher incidence of extratemporal seizure onset. Refractoriness seems to be more associated with other abnormalities, like HS or MCD, than with the HF variation itself. Thus, although morphological HF abnormalities might play a role in epileptogenicity, they seem to contribute less to refractoriness.

  3. Genetics Home Reference: focal dermal hypoplasia

    MedlinePlus

    ... Home Health Conditions focal dermal hypoplasia focal dermal hypoplasia Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description Focal dermal hypoplasia is a genetic disorder that primarily affects the ...

  4. Preoperative automated fibre quantification predicts postoperative seizure outcome in temporal lobe epilepsy

    PubMed Central

    Glenn, G. Russell; Weber, Bernd; Kreilkamp, Barbara A. K.; Jensen, Jens H.; Helpern, Joseph A.; Wagner, Jan; Barker, Gareth J.; Richardson, Mark P.; Bonilha, Leonardo

    2017-01-01

    Approximately one in every two patients with pharmacoresistant temporal lobe epilepsy will not be rendered completely seizure-free after temporal lobe surgery. The reasons for this are unknown and are likely to be multifactorial. Quantitative volumetric magnetic resonance imaging techniques have provided limited insight into the causes of persistent postoperative seizures in patients with temporal lobe epilepsy. The relationship between postoperative outcome and preoperative pathology of white matter tracts, which constitute crucial components of epileptogenic networks, is unknown. We investigated regional tissue characteristics of preoperative temporal lobe white matter tracts known to be important in the generation and propagation of temporal lobe seizures in temporal lobe epilepsy, using diffusion tensor imaging and automated fibre quantification. We studied 43 patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis and 44 healthy controls. Patients underwent preoperative imaging, amygdalohippocampectomy and postoperative assessment using the International League Against Epilepsy seizure outcome scale. From preoperative imaging, the fimbria-fornix, parahippocampal white matter bundle and uncinate fasciculus were reconstructed, and scalar diffusion metrics were calculated along the length of each tract. Altogether, 51.2% of patients were rendered completely seizure-free and 48.8% continued to experience postoperative seizure symptoms. Relative to controls, both patient groups exhibited strong and significant diffusion abnormalities along the length of the uncinate bilaterally, the ipsilateral parahippocampal white matter bundle, and the ipsilateral fimbria-fornix in regions located within the medial temporal lobe. However, only patients with persistent postoperative seizures showed evidence of significant pathology of tract sections located in the ipsilateral dorsal fornix and in the contralateral parahippocampal white matter bundle

  5. Protective effect of hispidulin on kainic acid-induced seizures and neurotoxicity in rats.

    PubMed

    Lin, Tzu Yu; Lu, Cheng Wei; Wang, Su Jane; Huang, Shu Kuei

    2015-05-15

    Hispidulin is a flavonoid compound which is an active ingredient in a number of traditional Chinese medicinal herbs, and it has been reported to inhibit glutamate release. The purpose of this study was to investigate whether hispidulin protects against seizures induced by kainic acid, a glutamate analog with excitotoxic properties. The results indicated that intraperitoneally administering hispidulin (10 or 50mg/kg) to rats 30 min before intraperitoneally injecting kainic acid (15 mg/kg) increased seizure latency and decreased seizure score. In addition, hispidulin substantially attenuated kainic acid-induced hippocampal neuronal cell death, and this protective effect was accompanied by the suppression of microglial activation and the production of proinflammatory cytokines such as interleukin-1β, interleukin-6, and tumor necrosis factor-α in the hippocampus. Moreover, hispidulin reduced kainic acid-induced c-Fos expression and the activation of mitogen-activated protein kinases in the hippocampus. These data suggest that hispidulin has considerable antiepileptic, neuroprotective, and antiinflammatory effects on kainic acid-induced seizures in rats.

  6. Toward a probabilistic definition of seizures.

    PubMed

    Osorio, Ivan; Lyubushin, Alexey; Sornette, Didier

    2011-12-01

    This writing (1) draws attention to the intricacies inherent to the pursuit of a universal seizure definition even when powerful, well-understood signal analysis methods are used to this end; (2) identifies this aim as a multi-objective optimization problem and discusses the advantages and disadvantages of adopting or rejecting a unitary seizure definition; and (3) introduces a probabilistic measure of seizure activity to manage this thorny issue. The challenges posed by the attempt to define seizures unitarily may be partly related to their fractal properties and understood through a simplistic analogy to the so-called "Richardson effect." A revision of the time-honored conceptualization of seizures may be warranted to further advance epileptology. This article is part of a Supplemental Special Issue entitled The Future of Automated Seizure Detection and Prediction.

  7. Role of subdural electrocorticography in prediction of long-term seizure outcome in epilepsy surgery

    PubMed Central

    Juhász, Csaba; Shah, Aashit; Sood, Sandeep; Chugani, Harry T.

    2009-01-01

    Since prediction of long-term seizure outcome using preoperative diagnostic modalities remains suboptimal in epilepsy surgery, we evaluated whether interictal spike frequency measures obtained from extraoperative subdural electrocorticography (ECoG) recording could predict long-term seizure outcome. This study included 61 young patients (age 0.4–23.0 years), who underwent extraoperative ECoG recording prior to cortical resection for alleviation of uncontrolled focal seizures. Patient age, frequency of preoperative seizures, neuroimaging findings, ictal and interictal ECoG measures were preoperatively obtained. The seizure outcome was prospectively measured [follow-up period: 2.5–6.4 years (mean 4.6 years)]. Univariate and multivariate logistic regression analyses determined how well preoperative demographic and diagnostic measures predicted long-term seizure outcome. Following the initial cortical resection, Engel Class I, II, III and IV outcomes were noted in 35, 6, 12 and 7 patients, respectively. One child died due to disseminated intravascular coagulation associated with pseudomonas sepsis 2 days after surgery. Univariate regression analyses revealed that incomplete removal of seizure onset zone, higher interictal spike-frequency in the preserved cortex and incomplete removal of cortical abnormalities on neuroimaging were associated with a greater risk of failing to obtain Class I outcome. Multivariate logistic regression analysis revealed that incomplete removal of seizure onset zone was the only independent predictor of failure to obtain Class I outcome. The goodness of regression model fit and the predictive ability of regression model were greatest in the full regression model incorporating both ictal and interictal measures [R2 0.44; Area under the receiver operating characteristic (ROC) curve: 0.81], slightly smaller in the reduced model incorporating ictal but not interictal measures (R2 0.40; Area under the ROC curve: 0.79) and slightly smaller

  8. Preictal Activity of Subicular, CA1, and Dentate Gyrus Principal Neurons in the Dorsal Hippocampus before Spontaneous Seizures in a Rat Model of Temporal Lobe Epilepsy

    PubMed Central

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

    2014-01-01

    Previous studies suggest that spontaneous seizures in patients with temporal lobe epilepsy might be preceded by increased action potential firing of hippocampal neurons. Preictal activity is potentially important because it might provide new opportunities for predicting when a seizure is about to occur and insight into how spontaneous seizures are generated. We evaluated local field potentials and unit activity of single, putative excitatory neurons in the subiculum, CA1, CA3, and dentate gyrus of the dorsal hippocampus in epileptic pilocarpine-treated rats as they experienced spontaneous seizures. Average action potential firing rates of neurons in the subiculum, CA1, and dentate gyrus, but not CA3, increased significantly and progressively beginning 2–4 min before locally recorded spontaneous seizures. In the subiculum, CA1, and dentate gyrus, but not CA3, 41–57% of neurons displayed increased preictal activity with significant consistency across multiple seizures. Much of the increased preictal firing of neurons in the subiculum and CA1 correlated with preictal theta activity, whereas preictal firing of neurons in the dentate gyrus was independent of theta. In addition, some CA1 and dentate gyrus neurons displayed reduced firing rates preictally. These results reveal that different hippocampal subregions exhibit differences in the extent and potential underlying mechanisms of preictal activity. The finding of robust and significantly consistent preictal activity of subicular, CA1, and dentate neurons in the dorsal hippocampus, despite the likelihood that many seizures initiated in other brain regions, suggests the existence of a broader neuronal network whose activity changes minutes before spontaneous seizures initiate. PMID:25505320

  9. Seizure characteristics in Pallister-Killian syndrome.

    PubMed

    Candee, Meghan S; Carey, John C; Krantz, Ian D; Filloux, Francis M

    2012-12-01

    Pallister-Killian syndrome (PKS) is a congenital disorder attributed to supernumerary isochromosome 12p mosaicism. Craniofacial dysmorphism, learning impairment and seizures are considered cardinal features. However, little is known regarding the seizure and epilepsy patterns in PKS. To better define the prevalence and spectrum of seizures in PKS, we studied 51 patients (39 male, 12 female; median age 4 years and 9 months; age range 7 months to 31 years) with confirmed 12p tetrasomy. Using a parent-based structured questionnaire, we collected data regarding seizure onset, frequency, timing, semiology, and medication therapy. Patients were recruited through our practice, at PKS Kids family events, and via the PKS Kids website. Epilepsy occurred in 27 (53%) with 23 (85%) of those with seizures having seizure onset prior to 3.5 years of age. Mean age at seizure onset was 2 years and 4 months. The most common seizure types were myoclonic (15/27, 56%), generalized convulsions (13/27, 48%), and clustered tonic spasms (similar to infantile spasms; 8/27, 30%). Thirteen of 27 patients with seizures (48%) had more than one seizure type with 26 out of 27 (96%) ever having taken antiepileptic medications. Nineteen of 27 (70%) continued to have seizures and 17/27 (63%) remained on antiepileptic medication. The most commonly used medications were: levetiracetam (10/27, 37%), valproic acid (10/27, 37%), and topiramate (9/27, 33%) with levetiracetam felt to be "most helpful" by parents (6/27, 22%). Further exploration of seizure timing, in-depth analysis of EEG recordings, and collection of MRI data to rule out confounding factors is warranted.

  10. Fiber Tract Stimulation Can Reduce Epileptiform Activity in an in-vitro Bilateral Hippocampal Slice Preparation

    PubMed Central

    Toprani, Sheela; Durand, Dominique

    2012-01-01

    Mesial temporal lobe epilepsy (MTLE) is a common medically refractory neurological disease that has been treated with electrical stimulation of gray matter with limited success. However, stimulation of a white matter tract connecting the hippocampi could maximize treatment efficacy and extent. We tested low-frequency stimulation (LFS) of a novel target that enables simultaneous targeting of bilateral hippocampi: the ventral hippocampal commissure (VHC) with a novel in-vitro slice preparation containing bilateral hippocampi connected by the VHC. The goal of this study is to understand the role of hippocampal interplay in seizure propagation and reduction by commissural fiber tract stimulation. LFS is applied to the VHC as extracellular and intracellular recording techniques are combined with signal processing to estimate several metrics of epilepsy including: (1) total time occupied by seizure activity (%); (2) seizure duration (s); (3) seizures per minute (#); and (4) power in the ictal (V2Hz−1); as well as (5) interictal spectra (V2Hz−1). Bilateral epileptiform activity in this preparation is highly correlated between hippocampi. Application of LFS to the VHC reduces all metrics of epilepsy during treatment in an amplitude and frequency dependent manner. This study lends several insights into the mechanisms of bilateral seizure reduction by LFS of the VHC, including that depolarization blocking, LTD/LTP and GABAA are not involved. Importantly, enhanced post-stimulation 1-Hz spiking correlates with long-lasting seizure reduction and both are heightened by targeting bilateral hippocampi via the VHC. Therefore, stimulating bilateral hippocampi via a single electrode in the VHC may provide an effective MTLE treatment. PMID:23123405

  11. Direct Imaging of Hippocampal Epileptiform Calcium Motifs Following Kainic Acid Administration in Freely Behaving Mice

    PubMed Central

    Berdyyeva, Tamara K.; Frady, E. Paxon; Nassi, Jonathan J.; Aluisio, Leah; Cherkas, Yauheniya; Otte, Stephani; Wyatt, Ryan M.; Dugovic, Christine; Ghosh, Kunal K.; Schnitzer, Mark J.; Lovenberg, Timothy; Bonaventure, Pascal

    2016-01-01

    Prolonged exposure to abnormally high calcium concentrations is thought to be a core mechanism underlying hippocampal damage in epileptic patients; however, no prior study has characterized calcium activity during seizures in the live, intact hippocampus. We have directly investigated this possibility by combining whole-brain electroencephalographic (EEG) measurements with microendoscopic calcium imaging of pyramidal cells in the CA1 hippocampal region of freely behaving mice treated with the pro-convulsant kainic acid (KA). We observed that KA administration led to systematic patterns of epileptiform calcium activity: a series of large-scale, intensifying flashes of increased calcium fluorescence concurrent with a cluster of low-amplitude EEG waveforms. This was accompanied by a steady increase in cellular calcium levels (>5 fold increase relative to the baseline), followed by an intense spreading calcium wave characterized by a 218% increase in global mean intensity of calcium fluorescence (n = 8, range [114–349%], p < 10−4; t-test). The wave had no consistent EEG phenotype and occurred before the onset of motor convulsions. Similar changes in calcium activity were also observed in animals treated with 2 different proconvulsant agents, N-methyl-D-aspartate (NMDA) and pentylenetetrazol (PTZ), suggesting the measured changes in calcium dynamics are a signature of seizure activity rather than a KA-specific pathology. Additionally, despite reducing the behavioral severity of KA-induced seizures, the anticonvulsant drug valproate (VA, 300 mg/kg) did not modify the observed abnormalities in calcium dynamics. These results confirm the presence of pathological calcium activity preceding convulsive motor seizures and support calcium as a candidate signaling molecule in a pathway connecting seizures to subsequent cellular damage. Integrating in vivo calcium imaging with traditional assessment of seizures could potentially increase translatability of pharmacological

  12. Seizure-induced alterations in fast-spiking basket cell GABA currents modulate frequency and coherence of gamma oscillation in network simulations

    SciTech Connect

    Proddutur, Archana; Yu, Jiandong; Elgammal, Fatima S.; Santhakumar, Vijayalakshmi

    2013-12-15

    FS-BC frequency when E{sub GABA} was depolarizing (−54 mV). When FS-BCs were activated by biologically based dendritic synaptic inputs, enhancing g{sub GABA-extra} reduced the frequency and coherence of FS-BC firing when E{sub GABA} was shunting and increased average FS-BC firing when E{sub GABA} was depolarizing. Shifting E{sub GABA} from shunting to depolarizing potentials consistently increased network frequency to and above high gamma frequencies (>80 Hz). Since gamma oscillations may contribute to learning and memory processing [Fell et al., Nat. Neurosci. 4, 1259 (2001); Jutras et al., J. Neurosci. 29, 12521 (2009); Wang, Physiol. Rev. 90, 1195 (2010)], our demonstration that network oscillations are modulated by extrasynaptic inhibition in FS-BCs suggests that neuroactive compounds that act on extrasynaptic GABA receptors could impact memory formation by modulating hippocampal gamma oscillations. The simulation results indicate that the depolarized FS-BC GABA reversal, observed after experimental seizures, together with enhanced spillover extrasynaptic GABA currents are likely to promote generation of focal high frequency activity associated with epileptic networks.

  13. Seizure-induced alterations in fast-spiking basket cell GABA currents modulate frequency and coherence of gamma oscillation in network simulations

    NASA Astrophysics Data System (ADS)

    Proddutur, Archana; Yu, Jiandong; Elgammal, Fatima S.; Santhakumar, Vijayalakshmi

    2013-12-01

    (-54 mV). When FS-BCs were activated by biologically based dendritic synaptic inputs, enhancing gGABA-extra reduced the frequency and coherence of FS-BC firing when EGABA was shunting and increased average FS-BC firing when EGABA was depolarizing. Shifting EGABA from shunting to depolarizing potentials consistently increased network frequency to and above high gamma frequencies (>80 Hz). Since gamma oscillations may contribute to learning and memory processing [Fell et al., Nat. Neurosci. 4, 1259 (2001); Jutras et al., J. Neurosci. 29, 12521 (2009); Wang, Physiol. Rev. 90, 1195 (2010)], our demonstration that network oscillations are modulated by extrasynaptic inhibition in FS-BCs suggests that neuroactive compounds that act on extrasynaptic GABA receptors could impact memory formation by modulating hippocampal gamma oscillations. The simulation results indicate that the depolarized FS-BC GABA reversal, observed after experimental seizures, together with enhanced spillover extrasynaptic GABA currents are likely to promote generation of focal high frequency activity associated with epileptic networks.

  14. A seizure response dog: video recording of reacting behaviour during repetitive prolonged seizures.

    PubMed

    Di Vito, Lidia; Naldi, Ilaria; Mostacci, Barbara; Licchetta, Laura; Bisulli, Francesca; Tinuper, Paolo

    2010-06-01

    Seizure response and alerting behaviour may spontaneously develop in dogs living with children or adults with epilepsy. Some dogs can also be reliably trained to respond and anticipate seizures. We describe the case of a dog, not previously trained for assistance work, showing complex seizure response behaviour. This is the first release of a home video recording of a dog reacting to its owner's seizure.

  15. Statistical Earthquake Focal Mechanism Forecasts

    NASA Astrophysics Data System (ADS)

    Kagan, Y. Y.; Jackson, D. D.

    2013-12-01

    The new whole Earth focal mechanism forecast, based on the GCMT catalog, has been created. In the present forecast, the sum of normalized seismic moment tensors within 1000 km radius is calculated and the P- and T-axes for the focal mechanism are evaluated on the basis of the sum. Simultaneously we calculate an average rotation angle between the forecasted mechanism and all the surrounding mechanisms. This average angle shows tectonic complexity of a region and indicates the accuracy of the prediction. The method was originally proposed by Kagan and Jackson (1994, JGR). Recent interest by CSEP and GEM has motivated some improvements, particularly to extend the previous forecast to polar and near-polar regions. The major problem in extending the forecast is the focal mechanism calculation on a spherical surface. In the previous forecast as our average focal mechanism was computed, it was assumed that longitude lines are approximately parallel within 1000 km radius. This is largely accurate in the equatorial and near-equatorial areas. However, when one approaches the 75 degree latitude, the longitude lines are no longer parallel: the bearing (azimuthal) difference at points separated by 1000 km reach about 35 degrees. In most situations a forecast point where we calculate an average focal mechanism is surrounded by earthquakes, so a bias should not be strong due to the difference effect cancellation. But if we move into polar regions, the bearing difference could approach 180 degrees. In a modified program focal mechanisms have been projected on a plane tangent to a sphere at a forecast point. New longitude axes which are parallel in the tangent plane are corrected for the bearing difference. A comparison with the old 75S-75N forecast shows that in equatorial regions the forecasted focal mechanisms are almost the same, and the difference in the forecasted focal mechanisms rotation angle is close to zero. However, though the forecasted focal mechanisms are similar

  16. Cellular and network mechanisms of electrographic seizures

    PubMed Central

    Bazhenov, Maxim; Timofeev, Igor; Fröhlich, Flavio; Sejnowski, Terrence J.

    2008-01-01

    Epileptic seizures constitute a complex multiscale phenomenon that is characterized by synchronized hyperexcitation of neurons in neuronal networks. Recent progress in understanding pathological seizure dynamics provides crucial insights into underlying mechanisms and possible new avenues for the development of novel treatment modalities. Here we review some recent work that combines in vivo experiments and computational modeling to unravel the pathophysiology of seizures of cortical origin. We particularly focus on how activity-dependent changes in extracellular potassium concentration affects the intrinsic dynamics of neurons involved in cortical seizures characterized by spike/wave complexes and fast runs. PMID:19190736

  17. Structural imaging of hippocampal subfields in healthy aging and Alzheimer's disease.

    PubMed

    de Flores, Robin; La Joie, Renaud; Chételat, Gaël

    2015-11-19

    Hippocampal atrophy, as evidenced using magnetic resonance imaging (MRI), is one of the most validated, easily accessible and widely used biomarkers of Alzheimer's disease (AD). However, its imperfect sensitivity and specificity have highlighted the need to improve the analysis of MRI data. Based on neuropathological data showing a differential vulnerability of hippocampal subfields to AD processes, neuroimaging researchers have tried to capture corresponding morphological changes within the hippocampus. The present review provides an overview of the methodological developments that allow the assessment of hippocampal subfield morphology in vivo, and summarizes the results of studies looking at the effects of AD and normal aging on these structures. Most studies highlighted a focal atrophy of the CA1 subfield in the early (predementia or even preclinical) stages of AD, before atrophy becomes more widespread at the dementia stage, consistent with the pathological literature. Preliminary studies have indicated that looking at this focal atrophy pattern rather than standard whole hippocampus volumetry improves diagnostic accuracy at the mild cognitive impairment (MCI) stage. However, controversies remain regarding changes in hippocampal subfield structure in normal aging and regarding correlations between specific subfield volume and memory abilities, very likely because of the strong methodological variability between studies. Overall, hippocampal subfield analysis has proven to be a promising technique in the study of AD. However, harmonization of segmentation protocols and studies on larger samples are needed to enable accurate comparisons between studies and to confirm the clinical utility of these techniques.

  18. Nonepileptic seizures treatment workshop summary☆

    PubMed Central

    LaFrance, W. Curt; Alper, Kenneth; Babcock, Debra; Barry, John J.; Benbadis, Selim; Caplan, Rochelle; Gates, John; Jacobs, Margaret; Kanner, Andres; Martin, Roy; Rundhaugen, Lynn; Stewart, Randy; Vert, Christina

    2009-01-01

    In May 2005, an international, interdisciplinary group of researchers gathered in Bethesda, MD, USA, for a workshop to discuss the development of treatments for patients with nonepileptic seizures (NES). Specific subgroup topics that were covered included: pediatric NES; presenting the diagnosis of NES, outcome measures for NES trials; classification of NES subtypes; and pharmacological treatment approaches and psychotherapies. The intent was to develop specific research strategies that can be expanded to involve a large segment of the epilepsy and psychiatric treatment communities. Various projects have resulted from the workshop, including the initial development of a prospective randomized clinical trial for NES. PMID:16540377

  19. Brain state evolution during seizure and under anesthesia: a network-based analysis of stereotaxic eeg activity in drug-resistant epilepsy patients.

    PubMed

    Yaffe, Robert; Burns, Sam; Gale, John; Park, Hyun-Joo; Bulacio, Juan; Gonzalez-Martinez, Jorge; Sarma, Sridevi V

    2012-01-01

    Epilepsy is a neurological condition with a prevalence of 1%, and 14-34% have medically refractory epilepsy (MRE). Seizures in focal MRE are generated by a single epileptogenic zone (or focus), thus there is potentially a curative procedure - surgical resection. This procedure depends significantly on correct identification of the focus, which is often uncertain in clinical practice. In this study, we analyzed intracranial stereotaxic EEG (sEEG) data recorded in two human patients with drug-resistant epilepsy prior to undergoing resection surgery. We view the sEEG data as samples from the brain network and hypothesize that seizure foci can be identified based on their network connectivity during seizure. Specifically, we computed a time sequence of connectivity matrices from EEG recordings that represent network structure over time. For each patient, connectivity between electrodes was measured using the coherence in a given frequency band. Matrix structure was analyzed using singular value decomposition and the leading singular vector was used to estimate each electrode's time dependent centrality (importance to the network's connectivity). Our preliminary study suggests that seizure foci may be the most weakly connected regions in the brain during the beginning of a seizure and the most strongly connected regions towards the end of a seizure. Additionally, in one of the patients analyzed, the network connectivity under anesthesia highlights seizure foci. Ultimately, network centrality computed from sEEG activity may be used to develop an automated, reliable, and computationally efficient algorithm for identifying seizure foci.

  20. Repeat surgery for focal cortical dysplasias in children: indications and outcomes.

    PubMed

    Sacino, Matthew F; Ho, Cheng-Ying; Whitehead, Matthew T; Kao, Amy; Depositario-Cabacar, Dewi; Myseros, John S; Magge, Suresh N; Keating, Robert F; Gaillard, William D; Oluigbo, Chima O

    2017-02-01

    OBJECTIVE Focal cortical dysplasia (FCD) is a common cause of medically intractable epilepsy that often may be treated by surgery. Following resection, many patients continue to experience seizures, necessitating a decision for further surgery to achieve the desired seizure outcomes. Few studies exist on the efficacy of reoperation for intractable epilepsy due to FCD in pediatric cohorts, including the definition of prognostic factors correlated with clinical benefit from further resection. METHODS The authors retrospectively analyzed the medical records and MR images of 22 consecutive pediatric patients who underwent repeat FCD resection after unsuccessful first surgery at the Children's National Health System between March 2005 and April 2015. RESULTS Accounting for all reoperations, 13 (59%) of the 22 patients achieved complete seizure freedom and another 5 patients (23%) achieved significant improvement in seizure control. Univariate analysis demonstrated that concordance in electrocorticography (ECoG) and MRI localization (p = 0.005), and completeness of resection (p = 0.0001), were associated with seizure freedom after the first reoperation. Patients with discordant ECoG and MRI findings ultimately benefited from aggressive multilobe lobectomy or hemispherectomy. Repeat lesionectomies utilizing intraoperative MRI (iMRI; n = 9) achieved complete resection and seizure freedom in all cases. CONCLUSIONS Reoperation may be clinically beneficial in patients with intractable epilepsy due to FCD. Patients with concordant intraoperative ECoG and MRI localization may benefit from extended resection of residual dysplasia at the margins of the previous lesional cavity, and iMRI may offer benefits as a quality control mechanism to ensure that a complete resection has been accomplished. Patients with discordant findings may benefit from more aggressive resections at earlier stages to achieve better seizure control and ensure functional plasticity.

  1. Seizures

    MedlinePlus

    ... Street drugs, such as angel dust (PCP), cocaine, amphetamines Stroke Toxemia of pregnancy Toxin buildup in the ... Tests that may be ordered include: Blood tests CT scan of the head or MRI of the ...

  2. A hardware-algorithm co-design approach to optimize seizure detection algorithms for implantable applications.

    PubMed

    Raghunathan, Shriram; Gupta, Sumeet K; Markandeya, Himanshu S; Roy, Kaushik; Irazoqui, Pedro P

    2010-10-30

    Implantable neural prostheses that deliver focal electrical stimulation upon demand are rapidly emerging as an alternate therapy for roughly a third of the epileptic patient population that is medically refractory. Seizure detection algorithms enable feedback mechanisms to provide focally and temporally specific intervention. Real-time feasibility and computational complexity often limit most reported detection algorithms to implementations using computers for bedside monitoring or external devices communicating with the implanted electrodes. A comparison of algorithms based on detection efficacy does not present a complete picture of the feasibility of the algorithm with limited computational power, as is the case with most battery-powered applications. We present a two-dimensional design optimization approach that takes into account both detection efficacy and hardware cost in evaluating algorithms for their feasibility in an implantable application. Detection features are first compared for their ability to detect electrographic seizures from micro-electrode data recorded from kainate-treated rats. Circuit models are then used to estimate the dynamic and leakage power consumption of the compared features. A score is assigned based on detection efficacy and the hardware cost for each of the features, then plotted on a two-dimensional design space. An optimal combination of compared features is used to construct an algorithm that provides maximal detection efficacy per unit hardware cost. The methods presented in this paper would facilitate the development of a common platform to benchmark seizure detection algorithms for comparison and feasibility analysis in the next generation of implantable neuroprosthetic devices to treat epilepsy.

  3. Treatment of drug-induced seizures.

    PubMed

    Chen, Hsien-Yi; Albertson, Timothy E; Olson, Kent R

    2016-03-01

    Seizures are a common complication of drug intoxication, and up to 9% of status epilepticus cases are caused by a drug or poison. While the specific drugs associated with drug-induced seizures may vary by geography and change over time, common reported causes include antidepressants, stimulants and antihistamines. Seizures occur generally as a result of inadequate inhibitory influences (e.g., gamma aminobutyric acid, GABA) or excessive excitatory stimulation (e.g. glutamate) although many other neurotransmitters play a role. Most drug-induced seizures are self-limited. However, status epilepticus occurs in up to 10% of cases. Prolonged or recurrent seizures can lead to serious complications and require vigorous supportive care and anticonvulsant drugs. Benzodiazepines are generally accepted as the first line anticonvulsant therapy for drug-induced seizures. If benzodiazepines fail to halt seizures promptly, second line drugs include barbiturates and propofol. If isoniazid poisoning is a possibility, pyridoxine is given. Continuous infusion of one or more anticonvulsants may be required in refractory status epilepticus. There is no role for phenytoin in the treatment of drug-induced seizures. The potential role of ketamine and levetiracetam is promising but not established.

  4. Search and Seizure in the Schools

    ERIC Educational Resources Information Center

    Staros, Kari; Williams, Charles F.

    2007-01-01

    The Fourth Amendment to the U.S. Constitution protects the people of the United States from unreasonable searches and seizures. On first reading, these protections seem clearly defined. The amendment was meant to protect Americans from the kinds of random searches and seizures that the colonists experienced under British colonial rule. Under…

  5. Febrile Seizures and Epilepsy: Possible Outcomes

    MedlinePlus

    ... Childhood Epilepsy (PACE) practice guideline for the long-term management of the http://www.paceusa.org child with ... on Quality Improvement and tensen J. The long-term risk of epilepsy after febrile seizures in Management SboFSAAoP. Febrile seizures: clinical susceptible subgroups. Am J ...

  6. Oxygen and seizure dynamics: II. Computational modeling

    PubMed Central

    Wei, Yina; Ullah, Ghanim; Ingram, Justin

    2014-01-01

    Electrophysiological recordings show intense neuronal firing during epileptic seizures leading to enhanced energy consumption. However, the relationship between oxygen metabolism and seizure patterns has not been well studied. Recent studies have developed fast and quantitative techniques to measure oxygen microdomain concentration during seizure events. In this article, we develop a biophysical model that accounts for these experimental observations. The model is an extension of the Hodgkin-Huxley formalism and includes the neuronal microenvironment dynamics of sodium, potassium, and oxygen concentrations. Our model accounts for metabolic energy consumption during and following seizure events. We can further account for the experimental observation that hypoxia can induce seizures, with seizures occurring only within a narrow range of tissue oxygen pressure. We also reproduce the interplay between excitatory and inhibitory neurons seen in experiments, accounting for the different oxygen levels observed during seizures in excitatory vs. inhibitory cell layers. Our findings offer a more comprehensive understanding of the complex interrelationship among seizures, ion dynamics, and energy metabolism. PMID:24671540

  7. Seizure phenotypes, periodicity, and sleep-wake pattern of seizures in Kcna-1 null mice.

    PubMed

    Wright, Samantha; Wallace, Eli; Hwang, Youngdeok; Maganti, Rama

    2016-02-01

    This study was undertaken to describe seizure phenotypes, natural progression, sleep-wake patterns, as well as periodicity of seizures in Kcna-1 null mutant mice. These mice were implanted with epidural electroencephalography (EEG) and electromyography (EMG) electrodes, and simultaneous video-EEG recordings were obtained while animals were individually housed under either diurnal (LD) condition or constant darkness (DD) over ten days of recording. The video-EEG data were analyzed to identify electrographic and behavioral phenotypes and natural progression and to examine the periodicity of seizures. Sleep-wake patterns were analyzed to understand the distribution and onset of seizures across the sleep-wake cycle. Four electrographically and behaviorally distinct seizure types were observed. Regardless of lighting condition that animals were housed in, Kcna-1 null mice initially expressed only a few of the most severe seizure types that progressively increased in frequency and decreased in seizure severity. In addition, a circadian periodicity was noted, with seizures peaking in the first 12h of the Zeitgeber time (ZT) cycle, regardless of lighting conditions. Interestingly, seizure onset differed between lighting conditions where more seizures arose out of sleep in LD conditions, whereas under DD conditions, the majority occurred out of the wakeful state. We suggest that this model be used to understand the circadian pattern of seizures as well as the pathophysiological implications of sleep and circadian disturbances in limbic epilepsies.

  8. Which Brain Regions are Important for Seizure Dynamics in Epileptic Networks? Influence of Link Identification and EEG Recording Montage on Node Centralities.

    PubMed

    Geier, Christian; Lehnertz, Klaus

    2017-02-01

    Nodes in large-scale epileptic networks that are crucial for seizure facilitation and termination can be regarded as potential targets for individualized focal therapies. Graph-theoretical approaches based on centrality concepts can help to identify such important nodes, however, they may be influenced by the way networks are derived from empirical data. Here we investigate evolving functional epileptic brain networks during 82 focal seizures with different anatomical onset locations that we derive from multichannel intracranial electroencephalographic recordings from 51 patients. We demonstrate how the various methodological steps (from the recording montage via node and link inference to the assessment of node centralities) affect importance estimation and discuss their impact on the interpretability of findings in the context of pathophysiological aspects of seizure dynamics.

  9. Gelastic seizures misdiagnosed as gastroesophageal reflux disease.

    PubMed

    Sweetman, Laura L; Ng, Yu-Tze; Kerrigan, John F

    2007-05-01

    Gastroesophageal reflux disease can have variable manifestations including regurgitation, irritability, arching, choking, and apnea. The disorder is also frequently mistaken for seizures (Sandifer syndrome). We report 6 patients in whom the opposite phenomenon occurred: their seizures were mistaken for gastroesophageal reflux disease. Six of 77 patients (6.8%) with gelastic seizures and epilepsy symptomatic of hypothalamic hamartomas were noted to be misdiagnosed with gastroesophageal reflux disease in infancy. As is typical in these patients, gelastic seizures were not diagnosed until months, or often years, later. Delayed diagnosis of hypothalamic hamartomas can lead to a potentially deleterious syndrome involving refractory epilepsy, developmental problems, and precocious puberty. Gelastic seizures should be considered among the conditions that can mimic reflux symptoms.

  10. Epileptic seizure induced by fennel essential oil.

    PubMed

    Skalli, Souad; Soulaymani Bencheikh, Rachida

    2011-09-01

    An epileptic seizure is reported in a 38-year-old woman, known to be an epileptic patient. Although she was under antiepileptic treatment and had well-controlled epilepsy, she developed a typical generalised tonic-clonic seizure and remained unconscious for 45 minutes following ingestion of a number of cakes containing an unknown quantity of fennel essential oil. Involuntary diarrhoea accompanied her epileptic seizure. This reported case recalls the fact that fennel essential oil can induce seizures and that this oil should probably be avoided by patients with epilepsy. Labelling of products with fennel essential oil should refer to the risk of seizures, particularly for patients with epilepsy. An awareness programme should involve all stakeholders affected by this issue.

  11. Forecasting Seizures Using Intracranial EEG Measures and SVM in Naturally Occurring Canine Epilepsy.

    PubMed

    Brinkmann, Benjamin H; Patterson, Edward E; Vite, Charles; Vasoli, Vincent M; Crepeau, Daniel; Stead, Matt; Howbert, J Jeffry; Cherkassky, Vladimir; Wagenaar, Joost B; Litt, Brian; Worrell, Gregory A

    2015-01-01

    Management of drug resistant focal epilepsy would be greatly assisted by a reliable warning system capable of alerting patients prior to seizures to allow the patient to adjust activities or medication. Such a system requires successful identification of a preictal, or seizure-prone state. Identification of preictal states in continuous long- duration intracranial electroencephalographic (iEEG) recordings of dogs with naturally occurring epilepsy was investigated using a support vector machine (SVM) algorithm. The dogs studied were implanted with a 16-channel ambulatory iEEG recording device with average channel reference for a mean (st. dev.) of 380.4 (+87.5) days producing 220.2 (+104.1) days of intracranial EEG recorded at 400 Hz for analysis. The iEEG records had 51.6 (+52.8) seizures identified, of which 35.8 (+30.4) seizures were preceded by more than 4 hours of seizure-free data. Recorded iEEG data were stratified into 11 contiguous, non-overlapping frequency bands and binned into one-minute synchrony features for analysis. Performance of the SVM classifier was assessed using a 5-fold cross validation approach, where preictal training data were taken from 90 minute windows with a 5 minute pre-seizure offset. Analysis of the optimal preictal training time was performed by repeating the cross validation over a range of preictal windows and comparing results. We show that the optimization of feature selection varies for each subject, i.e. algorithms are subject specific, but achieve prediction performance significantly better than a time-matched Poisson random predictor (p<0.05) in 5/5 dogs analyzed.

  12. Magnetoencephalography (MEG) predicts focal epileptogenicity in cavernomas

    PubMed Central

    Stefan, H; Scheler, G; Hummel, C; Walter, J; Romstock, J; Buchfelder, M; Blumcke, I

    2004-01-01

    Objective: The aim of this study was to identify the irritative epileptic zone in patients with cavernomas by means of magnetoencephalography (MEG). Method: Among 82 patients operated for epilepsy, whose presurgical evaluation had included MEG, histological assessment of the tissue removed had confirmed cavernomas in eight. These eight patients had epilepsy since 18.6 (SD 12.7) years on average. The monitoring lasted about 2.1 (SD 1.3) hours and a median 20.9 (SD 14.3) spikes per hour were recorded. Spontaneous brain activity was recorded by means of a 74 channel dual unit MEG system (Magnes II, 4-D Neuroimaging) with simultaneous EEG recording (31 scalp electrodes). Spike analysis was performed using different source (moving dipole, current density reconstruction) and head models (spherical shells, BEM). Co-registration of neurophysiological and imaging data (MRI) was based upon anatomical landmarks. Results: In 6/8 patients co-localisation from the cavernoma and epileptic zone was found. In two patients the focus was localised in the parieto-occipital lobe, in three patients in the frontal lobe and in three patients in the temporal lobe. In one case of temporal and one case of frontal lobe focus localisation there was no spatial relationship to the cavernoma. Conclusion: In cases of focal seizures due to a single cavernoma, MEG may precisely delineate the epileptogenic tissue bordering the lesion. In patients with multiple cavernomas or dual pathology, MSI may reveal the complexity of the case, and contribute to the decision about further invasive diagnostics and more sophisticated therapeutic measures. MEG is a promising method for prediction of the epileptic zone in cavernoma related epilepsies, and thus it can contribute to decision making about and planning of epilepsy surgery. PMID:15314122

  13. Prevention of epileptic seizures by taurine.

    PubMed

    El Idrissi, Abdeslem; Messing, Jeffrey; Scalia, Jason; Trenkner, Ekkhart

    2003-01-01

    Parenteral injection of kainic acid (KA), a glutamate receptor agonist, causes severe and stereotyped behavioral convulsions in mice and is used as a rodent model for human temporal lobe epilepsy. The goal of this study is to examine the potential anti-convulsive effects of the neuro-active amino acid taurine, in the mouse model of KA-induced limbic seizures. We found that taurine (43 mg/Kg, s.c.) had a significant antiepileptic effect when injected 10 min prior to KA. Acute injection of taurine increased the onset latency and reduced the occurrence of tonic seizures. Taurine also reduced the duration of tonic-clonic convulsions and mortality rate following KA-induced seizures. Furthermore, taurine significantly reduced neuronal cell death in the CA3 region of the hippocampus, the most susceptible region to KA in the limbic system. On the other hand, supplementation of taurine in drinking water (0.05%) for 4 continuous weeks failed to decrease the number or latency of partial or tonic-clonic seizures. To the contrary, we found that taurine-fed mice showed increased susceptibility to KA-induced seizures, as demonstrated by a decreased latency for clonic seizures, an increased incidence and duration of tonic-clonic seizures, increased neuronal death in the CA3 region of the hippocampus and a higher post-seizure mortality of the animals. We suggest that the reduced susceptibility to KA-induced seizures in taurine-injected mice is due to an increase in GABA receptor function in the brain which increases the inhibitory drive within the limbic system. This is supported by our in vitro data obtained in primary neuronal cultures showing that taurine acts as a low affinity agonist for GABA(A) receptors, protects neurons against kainate excitotoxic insults and modulates calcium homeostasis. Therefore, taurine is potentially capable of treating seizure-associated brain damage.

  14. Continuously variable focal length lens

    DOEpatents

    Adams, Bernhard W; Chollet, Matthieu C

    2013-12-17

    A material preferably in crystal form having a low atomic number such as beryllium (Z=4) provides for the focusing of x-rays in a continuously variable manner. The material is provided with plural spaced curvilinear, optically matched slots and/or recesses through which an x-ray beam is directed. The focal length of the material may be decreased or increased by increasing or decreasing, respectively, the number of slots (or recesses) through which the x-ray beam is directed, while fine tuning of the focal length is accomplished by rotation of the material so as to change the path length of the x-ray beam through the aligned cylindrical slows. X-ray analysis of a fixed point in a solid material may be performed by scanning the energy of the x-ray beam while rotating the material to maintain the beam's focal point at a fixed point in the specimen undergoing analysis.

  15. Genetic models of focal epilepsies.

    PubMed

    Boillot, Morgane; Baulac, Stéphanie

    2016-02-15

    Focal epilepsies were for a long time thought to be acquired disorders secondary to cerebral lesions. However, the important role of genetic factors in focal epilepsies is now well established. Several focal epilepsy syndromes are now proven to be monogenic disorders. While earlier genetic studies suggested a strong contribution of ion channel and neurotransmitter receptor genes, later work has revealed alternative pathways, among which the mammalian target of rapamycin (mTOR) signal transduction pathway with DEPDC5. In this article, we provide an update on the mutational spectrum of neuronal nicotinic acetylcholine receptor genes (CHRNA4, CHRNB2, CHRNA2) and KCNT1 causing autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), and of LGI1 in autosomal dominant epilepsy with auditory features (ADEAF). We also emphasize, through a review of the current literature, the contribution of in vitro and in vivo models developed to unveil the pathogenic mechanisms underlying these two epileptic syndromes.

  16. Lithium-methomyl induced seizures in rats: A new model of status epilepticus?

    SciTech Connect

    Kaminski, Rafal M. . E-mail: kaminskr@mail.nih.gov; Blaszczak, Piotr; Dekundy, Andrzej; Parada-Turska, Jolanta; Calderazzo, Lineu; Cavalheiro, Esper A.; Turski, Waldemar A.

    2007-03-15

    Behavioral, electroencephalographic (EEG) and neuropathological effects of methomyl, a carbamate insecticide reversibly inhibiting acetylcholinesterase activity, were studied in naive or lithium chloride (24 h, 3 mEq/kg, s.c.) pretreated male Wistar rats. In naive animals, methomyl with equal potency produced motor limbic seizures and fatal status epilepticus. Thus, the CD50 values (50% convulsant dose) for these seizure endpoints were almost equal to the LD50 (50% lethal dose) of methomyl (13 mg/kg). Lithium pretreated rats were much more susceptible to convulsant, but not lethal effect of methomyl. CD50 values of methomyl for motor limbic seizures and status epilepticus were reduced by lithium pretreatment to 3.7 mg/kg (a 3.5-fold decrease) and 5.2 mg/kg (a 2.5-fold decrease), respectively. In contrast, lithium pretreatment resulted in only 1.3-fold decrease of LD50 value of methomyl (9.9 mg/kg). Moreover, lithium-methomyl treated animals developed a long-lasting status epilepticus, which was not associated with imminent lethality observed in methomyl-only treated rats. Scopolamine (10 mg/kg) or diazepam (10 mg/kg) protected all lithium-methomyl treated rats from convulsions and lethality. Cortical and hippocampal EEG recordings revealed typical epileptic discharges that were consistent with behavioral seizures observed in lithium-methomyl treated rats. In addition, convulsions induced by lithium-methomyl treatment were associated with widespread neurodegeneration of limbic structures. Our observations indicate that lithium pretreatment results in separation between convulsant and lethal effects of methomyl in rats. As such, seizures induced by lithium-methomyl administration may be an alternative to lithium-pilocarpine model of status epilepticus, which is associated with high lethality.

  17. Lithium-methomyl induced seizures in rats: a new model of status epilepticus?

    PubMed

    Kaminski, Rafal M; Blaszczak, Piotr; Dekundy, Andrzej; Parada-Turska, Jolanta; Calderazzo, Lineu; Cavalheiro, Esper A; Turski, Waldemar A

    2007-03-01

    Behavioral, electroencephalographic (EEG) and neuropathological effects of methomyl, a carbamate insecticide reversibly inhibiting acetylcholinesterase activity, were studied in naive or lithium chloride (24 h, 3 mEq/kg, s.c.) pretreated male Wistar rats. In naive animals, methomyl with equal potency produced motor limbic seizures and fatal status epilepticus. Thus, the CD50 values (50% convulsant dose) for these seizure endpoints were almost equal to the LD50 (50% lethal dose) of methomyl (13 mg/kg). Lithium pretreated rats were much more susceptible to convulsant, but not lethal effect of methomyl. CD50 values of methomyl for motor limbic seizures and status epilepticus were reduced by lithium pretreatment to 3.7 mg/kg (a 3.5-fold decrease) and 5.2 mg/kg (a 2.5-fold decrease), respectively. In contrast, lithium pretreatment resulted in only 1.3-fold decrease of LD50 value of methomyl (9.9 mg/kg). Moreover, lithium-methomyl treated animals developed a long-lasting status epilepticus, which was not associated with imminent lethality observed in methomyl-only treated rats. Scopolamine (10 mg/kg) or diazepam (10 mg/kg) protected all lithium-methomyl treated rats from convulsions and lethality. Cortical and hippocampal EEG recordings revealed typical epileptic discharges that were consistent with behavioral seizures observed in lithium-methomyl treated rats. In addition, convulsions induced by lithium-methomyl treatment were associated with widespread neurodegeneration of limbic structures. Our observations indicate that lithium pretreatment results in separation between convulsant and lethal effects of methomyl in rats. As such, seizures induced by lithium-methomyl administration may be an alternative to lithium-pilocarpine model of status epilepticus, which is associated with high lethality.

  18. Critical Evaluation of P2X7 Receptor Antagonists in Selected Seizure Models

    PubMed Central

    Fischer, Wolfgang; Franke, Heike; Krügel, Ute; Müller, Heiko; Dinkel, Klaus; Lord, Brian; Letavic, Michael A.; Henshall, David C.; Engel, Tobias

    2016-01-01

    The ATP-gated P2X7 receptor (P2X7R) is a non-selective cation channel which senses high extracellular ATP concentrations and has been suggested as a target for the treatment of neuroinflammation and neurodegenerative diseases. The use of P2X7R antagonists may therefore be a viable approach for treating CNS pathologies, including epileptic disorders. Recent studies showed anticonvulsant potential of P2X7R antagonists in certain animal models. To extend this work, we tested three CNS-permeable P2X7R blocker (Brilliant Blue G, AFC-5128, JNJ-47965567) and a natural compound derivative (tanshinone IIA sulfonate) in four well-characterized animal seizure models. In the maximal electroshock seizure threshold test and the pentylenetetrazol (PTZ) seizure threshold test in mice, none of the four compounds demonstrated anticonvulsant effects when given alone. Notably, in combination with carbamazepine, both AFC-5128 and JNJ-47965567 increased the threshold in the maximal electroshock seizure test. In the PTZ-kindling model in rats, useful for testing antiepileptogenic activities, Brilliant Blue G and tanshinone exhibited a moderate retarding effect, whereas the potent P2X7R blocker AFC-5128 and JNJ-47965567 showed a significant and long-lasting delay in kindling development. In fully kindled rats, the investigated compounds revealed modest effects to reduce the mean seizure stage. Furthermore, AFC-5128- and JNJ-47965567-treated animals displayed strongly reduced Iba 1 and GFAP immunoreactivity in the hippocampal CA3 region. In summary, our results show that P2X7R antagonists possess no remarkable anticonvulsant effects in the used acute screening tests, but can attenuate chemically-induced kindling. Further studies would be of interest to support the concept that P2X7R signalling plays a crucial role in the pathogenesis of epileptic disorders. PMID:27281030

  19. Intractable gelastic seizures during infancy: ictal positron emission tomography (PET) demonstrating epileptiform activity within the hypothalamic hamartoma.

    PubMed

    Shahar, Eli; Goldsher, Dorit; Genizi, Jacob; Ravid, Sarit; Keidar, Zohar

    2008-02-01

    Gelastic seizures comprise a very rare form of epilepsy. They present with recurrent bursts of laughter voices without mirth and are most commonly associated with the evolution of a hypothalamic hamartoma. The purpose of this article is to describe the second reported ictal fluorodeoxyglucose-positron emission tomography study in a unique case of an infant with intractable gelastic seizures since the neonatal period associated with a hypothalamic hamartoma. The patient presented at 4 months old with recurrent, almost persistent, gelastic seizures consisting of laughter bouts without mirth. The seizures were noticeable at the first week of life and increased in frequency to last up to 12 hours, namely status gelasticus. These gelastic fits were accompanied with focal motor seizures, including unilateral right-eye blinking and mouth twitching. Developmental mile-stones were intact for age. Magnetic resonance imaging of the cortex demonstrated a large hypothalamic hamartoma within the third ventricle, hampering cerebrovascular fluid drainage of the lateral ventricles. An electroencephalography was nondiagnostic. Ictal fluorodeoxyglucose-positron emission tomography demonstrated a large circumscribed hypermetabolic region within the location of the hypothalamic hamartoma, representing localized intense epileptiform activity. The infant became instantly free of all seizure types given minute doses of oral benzodiazepine (clonazepam) and remains completely controlled after 12 months. Her overall development remains intact. This ictal fluorodeoxyglucose-positron emission tomography is the second reported study verifying that the main source of the epileptic activity inducing gelastic seizures originates from the hypothalamic hamartoma itself; therefore, a complementary fluorodeoxyglucose-positron emission tomography study should be considered in any patient presenting with intractable gelastic seizures, especially in those associated with hypothalamic hamartoma, in order

  20. Enduring Memory Impairments Provoked by Developmental Febrile Seizures Are Mediated by Functional and Structural Effects of Neuronal Restrictive Silencing Factor.

    PubMed

    Patterson, Katelin P; Barry, Jeremy M; Curran, Megan M; Singh-Taylor, Akanksha; Brennan, Gary; Rismanchi, Neggy; Page, Matias; Noam, Yoav; Holmes, Gregory L; Baram, Tallie Z

    2017-04-05

    In a subset of children experiencing prolonged febrile seizures (FSs), the most common type of childhood seizures, cognitive outcomes are compromised. However, the underlying mechanisms are unknown. Here we identified significant, enduring spatial memory problems in male rats following experimental prolonged FS (febrile status epilepticus; eFSE). Remarkably, these deficits were abolished by transient, post hoc interference with the chromatin binding of the transcriptional repressor neuron restrictive silencing factor (NRSF or REST). This transcriptional regulator is known to contribute to neuronal differentiation during development and to programmed gene expression in mature neurons. The mechanisms of the eFSE-provoked memory problems involved complex disruption of memory-related hippocampal oscillations recorded from CA1, likely resulting in part from impairments of dendritic filtering of cortical inputs as well as abnormal synaptic function. Accordingly, eFSE provoked region-specific dendritic loss in the hippocampus, and aberrant generation of excitatory synapses in dentate gyrus granule cells. Blocking NRSF transiently after eFSE prevented granule cell dysmaturation, restored a functional balance of γ-band network oscillations, and allowed treated eFSE rats to encode and retrieve spatial memories. Together, these studies provide novel insights into developing networks that underlie memory, the mechanisms by which early-life seizures influence them, and the means to abrogate the ensuing cognitive problems.SIGNIFICANCE STATEMENT Whereas seizures have been the central focus of epilepsy research, they are commonly accompanied by cognitive problems, including memory impairments that contribute to poor quality of life. These deficits often arise before the onset of spontaneous seizures, or independent from them, yet the mechanisms involved are unclear. Here, using a rodent model of common developmental seizures that provoke epilepsy in a subset of individuals, we

  1. Intranasal Delivery of miR-146a Mimics Delayed Seizure Onset in the Lithium-Pilocarpine Mouse Model

    PubMed Central

    Zhao, Jianghao; Liu, Tingting; Cai, Yujie; Zhou, Xu; Xing, Huaijie; Wang, Yan; Yin, Mingkang; Zhong, Wangtao; Liu, Zhou; Li, Keshen

    2017-01-01

    Unveiling the key mechanism of temporal lobe epilepsy (TLE) for the development of novel treatments is of increasing interest, and anti-inflammatory miR-146a is now considered a promising molecular target for TLE. In the current study, a C57BL/6 TLE mouse model was established using the lithium-pilocarpine protocol. The seizure degree was evaluated according to the Racine scale, and level 5 was considered the threshold for generalized convulsions. Animals were sacrificed to analyze the hippocampus at three time points (2 h and 4 and 8 weeks after pilocarpine administration to evaluate the acute, latent, and chronic phases, resp.). After intranasal delivery of miR-146a mimics (30 min before pilocarpine injection), the percent of animals with no induced seizures increased by 6.7%, the latency to generalized convulsions was extended, and seizure severity was reduced. Additionally, hippocampal damage was alleviated. While the relative miR-146a levels significantly increased, the expression of its target mRNAs (IRAK-1 and TRAF-6) and typical inflammatory modulators (NF-κB, TNF-α, IL-1β, and IL-6) decreased, supporting an anti-inflammatory role of miR-146a via the TLR pathway. This study is the first to demonstrate that intranasal delivery of miR-146a mimics can improve seizure onset and hippocampal damage in the acute phase of lithium-pilocarpine-induced seizures, which provides inflammation-based clues for the development of novel TLE treatments. PMID:28242958

  2. Seizure induces activation of multiple subtypes of neural progenitors and growth factors in hippocampus with neuronal maturation confined to dentate gyrus

    SciTech Connect

    Indulekha, Chandrasekharan L.; Sanalkumar, Rajendran; Thekkuveettil, Anoopkumar; James, Jackson

    2010-03-19

    Adult hippocampal neurogenesis is altered in response to different physiological and pathological stimuli. GFAP{sup +ve}/nestin{sup +ve} radial glial like Type-1 progenitors are considered to be the resident stem cell population in adult hippocampus. During neurogenesis these Type-1 progenitors matures to GFAP{sup -ve}/nestin{sup +ve} Type-2 progenitors and then to Type-3 neuroblasts and finally differentiates into granule cell neurons. In our study, using pilocarpine-induced seizure model, we showed that seizure initiated activation of multiple progenitors in the entire hippocampal area such as DG, CA1 and CA3. Seizure induction resulted in activation of two subtypes of Type-1 progenitors, Type-1a (GFAP{sup +ve}/nestin{sup +ve}/BrdU{sup +ve}) and Type-1b (GFAP{sup +ve}/nestin{sup +ve}/BrdU{sup -ve}). We showed that majority of Type-1b progenitors were undergoing only a transition from a state of dormancy to activated form immediately after seizures rather than proliferating, whereas Type-1a showed maximum proliferation by 3 days post-seizure induction. Type-2 (GFAP{sup -ve}/nestin{sup +ve}/BrdU{sup +ve}) progenitors were few compared to Type-1. Type-3 (DCX{sup +ve}) progenitors showed increased expression of immature neurons only in DG region by 3 days after seizure induction indicating maturation of progenitors happens only in microenvironment of DG even though progenitors are activated in CA1 and CA3 regions of hippocampus. Also parallel increase in growth factors expression after seizure induction suggests that microenvironmental niche has a profound effect on stimulation of adult neural progenitors.

  3. Focal epithelial hyperplasia: Case report.

    PubMed

    Puriene, Alina; Rimkevicius, Arunas; Gaigalas, Mindaugas

    2011-01-01

    The purpose of the present article is to present a 15 year-old patient with focal epithelial hyperplasia and to review the references on the subject-related etiological, pathological, diagnostic and treatment aspects. Focal epithelial hyperplasia is a rare human papilloma virus (HPV) related to oral lesion with very low frequency within our population. Surgical treatment with a biopsy was performed, acanthosis and parakeratosis are consistent histopathological features, since the patient had no history of sexual contact and HIV infection, the virus was probably acquired from environmental sources.

  4. Seizure Reduction through Interneuron-mediated Entrainment using Low Frequency Optical Stimulation

    PubMed Central

    Ladas, Thomas P.; Chiang, Chia-Chu; Gonzalez-Reyes, Luis E.; Nowak, Theodore; Durand, Dominique M.

    2015-01-01

    Low frequency electrical stimulation (LFS) can reduce neural excitability and suppress seizures in animals and patients with epilepsy. However the therapeutic outcome could benefit from the determination of the cell types involved in seizure suppression. We used optogenetic techniques to investigate the role of interneurons in LFS (1Hz) in the epileptogenic hippocampus. Optical low frequency stimulation (oLFS) was first used to activate the cation channel channelrhodopsin-2 (ChR2) in the Thy1-ChR2 transgenic mouse that expresses ChR2 in both excitatory and inhibitory neurons. We found that oLFS could effectively reduce epileptiform activity in the hippocampus through the activation of GAD-expressing hippocampal interneurons. This was confirmed using the VGAT-ChR2 transgenic mouse, allowing for selective optical activation of only GABA interneurons. Activating hippocampal interneurons through oLFS was found to cause entrainment of neural activity similar to electrical stimulation, but through a GABAA-mediated mechanism. These results confirm the robustness of the LFS paradigm and indicate that GABA interneurons play an unexpected role of shaping inter-ictal activity to decrease neural excitability in the hippocampus. PMID:25863022

  5. Porencephaly and cortical dysplasia as cause of seizures in a dog

    PubMed Central

    2012-01-01

    Background Seizures are a common problem in small animal neurology and it may be related to underlying diseases. Porencephaly is an extremely rare disorder, and in Veterinary Medicine it affects more often ruminants, with only few reports in dogs. Case presentation A one-year-old intact male Shih-Tzu dog was referred to Veterinary University Hospital with history of abnormal gait and generalized tonic-clonic seizures. Signs included hypermetria, abnormal nystagmus and increased myotatic reflexes. At necropsy, during the brain analysis, a cleft was observed in the left parietal and occipital lobes, creating a communication between the subarachnoid space and the left lateral ventricle, consistent with porencephaly; and also a focal atrophy of the caudal paravermal and vermal portions of the cerebellum. Furthermore, the histological examination showed cortical and cerebellar neuronal dysplasia. Conclusions Reports of seizures due to porencephaly are rare in dogs. In this case, the dog presented a group of brain abnormalities which per se or in assemblage could result in seizure manifestation. PMID:23269021

  6. A recurrent KCNT1 mutation in two sporadic cases with malignant migrating partial seizures in infancy.

    PubMed

    Ishii, Atsushi; Shioda, Mutsuki; Okumura, Akihisa; Kidokoro, Hiroyuki; Sakauchi, Masako; Shimada, Shino; Shimizu, Toshiaki; Osawa, Makiko; Hirose, Shinichi; Yamamoto, Toshiyuki

    2013-12-01

    We performed analysis of KCNT1 in two unrelated patients with malignant migrating partial seizures in infancy. Both patients had intractable focal seizures since two months of age. Their seizures were characterized by a shift of epileptic focus during a single seizure and were resistant to most antiepileptic drugs but responded to vagus nerve stimulation in one and clorazepate in the other. Bidirectional sequencing for KCNT1 was analyzed by standard Sanger sequencing method. A de novo c.862G>A (p.Gly288Ser) missense mutation was identified at the pore region of KCNT1 channel in both patients, whereas all KCNT1 mutations in the previous reports were identified mostly in the intracellular C-terminal region. Computational analysis suggested possible changes in the molecular structure and the ion channel property induced by the Gly288Ser mutation. Because the G-to-A transition was located at CG dinucleotide sequences as previously reported for KCNT1 mutations, the recurrent occurrence of de novo KCNT1 mutations indicated the hot spots of these locations.

  7. Morphological changes among hippocampal dentate granule cells exposed to early kindling-epileptogenesis

    PubMed Central

    Singh, Shatrunjai P.; He, Xiaoping; McNamara, James O.; Danzer, Steve C.

    2013-01-01

    Temporal lobe epilepsy is associated with changes in the morphology of hippocampal dentate granule cells. These changes are evident in numerous models that are associated with substantial neuron loss and spontaneous recurrent seizures. By contrast, previous studies have shown that in the kindling model, it is possible to administer a limited number of stimulations sufficient to produce a lifelong enhanced sensitivity to stimulus evoked seizures without associated spontaneous seizures and minimal neuronal loss. Here we examined whether stimulation of the amygdala sufficient to evoke five convulsive seizures (class IV or greater on Racine’s scale) produce morphological changes similar to those observed in models of epilepsy associated with substantial cell loss. The morphology of GFP-expressing granule cells from Thy-1 GFP mice was examined either one day or one month after the last evoked seizure. Interestingly, significant reductions in dendritic spine density were evident one day after the last seizure, the magnitude of which had diminished by one month. Further, there was an increase in the thickness of the granule cell layer one day after the last evoked seizure, which was absent a month later. We also observed an increase in the area of the proximal axon, which again returned to control levels a month later. No differences in the number of basal dendrites were detected at either time point. These findings demonstrate that the early stages of kindling epileptogenesis produce transient changes in the granule cell body layer thickness, molecular layer spine density and axon proximal area, but do not produce striking rearrangements of granule cell structure. PMID:23893783

  8. Treatment of acute and remote symptomatic seizures.

    PubMed

    Koppel, Barbara S

    2009-07-01

    In principle, the use of anticonvulsant drugs does not differ between acute and remote symptomatic seizures, but control of acute symptomatic seizures requires simultaneous treatment of the underlying etiology. Prevention of remote seizures when the risk is known to be high has been the subject of intense efforts at antiepileptogenesis, but the optimal duration of treatment after an injury is not yet known. Appropriate evaluation of a seizure depends on individual circumstances, but findings on examination, laboratory tests (serum electrolytes, magnesium, glucose, assessment of hepatic and renal function), and brain imaging (CT scan or MRI) are necessary to determine the most likely cause. Lumbar puncture is always required when there is suspicion of meningitis or encephalitis. Preferred medications for treatment of acute symptomatic seizures or status epilepticus are those available for intravenous use, such as benzodiazepines, fosphenytoin or phenytoin, valproate, levetiracetam, and phenobarbital. Diazepam is also available as a gel for rectal administration. Seizures that occur in patients with epilepsy because of missed antiepileptic drugs or inadequate serum levels should be treated with additional doses of their regular medications; loading doses can be administered with minimal toxicity in tolerant patients. Surgery is rarely necessary in the acute setting except for intracerebral lesions with rapidly rising intracranial pressure and impending herniation. After seizures are controlled, the provoking condition must also be determined and treated.

  9. Detecting Neonatal Seizures With Computer Algorithms.

    PubMed

    Temko, Andriy; Lightbody, Gordon

    2016-10-01

    It is now generally accepted that EEG is the only reliable way to accurately detect newborn seizures and, as such, prolonged EEG monitoring is increasingly being adopted in neonatal intensive care units. Long EEG recordings may last from several hours to a few days. With neurophysiologists not always available to review the EEG during unsociable hours, there is a pressing need to develop a reliable and robust automatic seizure detection method-a computer algorithm that can take the EEG signal, process it, and output information that supports clinical decision making. In this study, we review existing algorithms based on how the relevant seizure information is exploited. We start with commonly used methods to extract signatures from seizure signals that range from those that mimic the clinical neurophysiologist to those that exploit mathematical models of neonatal EEG generation. Commonly used classification methods are reviewed that are based on a set of rules and thresholds that are either heuristically tuned or automatically derived from the data. These are followed by techniques to use information about spatiotemporal seizure context. The usual errors in system design and validation are discussed. Current clinical decision support tools that have met regulatory requirements and are available to detect neonatal seizures are reviewed with progress and the outstanding challenges are outlined. This review discusses the current state of the art regarding automatic detection of neonatal seizures.

  10. Metabolic brain PET pattern underlying hyperkinetic seizures.

    PubMed

    Guedj, Eric; McGonigal, Aileen; Vaugier, Lisa; Mundler, Olivier; Bartolomei, Fabrice

    2012-09-01

    This study aims to contribute to the identification of selective brain regions involved in hyperkinetic behaviors. We studied the whole-brain voxel-based interictal metabolic 18FDG-PET pattern of 23 patients with hyperkinetic seizures, in comparison with both 15 healthy subjects similar for age and gender, and 23 patients without hyperkinetic seizures. Patients were in particular similar for the localization of the epileptogenic zone, this having been defined using stereoelectroencephalography (SEEG) when clinically indicated (15/23 patients with hyperkinetic seizures and 13/23 patients without hyperkinetic seizures). Using conjunction voxel-based analysis, patients with hyperkinetic seizures exhibited significant hypometabolism within bilateral midbrain and the right caudate head, in comparison both to healthy subjects (p<0.05, FDR-corrected for the voxel) and to patients without hyperkinetic seizures (p<0.0167, uncorrected for the voxel). Findings were secondarily confirmed separately in each subgroup of patients with frontal, temporal or posterior epilepsy. These findings argue for a specific subcortical metabolic impairment in patients with hyperkinetic seizures, within brain structures supposed to be involved in the generation of primitive motor programs.

  11. Acute onset of focal seizures, psychiatric features and confusion: a case of autoimmune encephalitis?

    PubMed Central

    Al-Diwani, Adam; Butterworth, Richard J; Nibber, Anjan; Lang, Bethan; Vincent, Angela; Irani, Sarosh R

    2012-01-01

    An elderly woman presented with disorganised thinking, unusual behaviour and clustered episodes of speech arrest accompanied by right-sided face and arm twitching. The following investigations were normal: interictal electroencephalography, brain MRI, cerebrospinal fluid viral PCR and cell count and voltage-gated potassium channel-complex, N-methyl-d-aspartate receptor, gamma-aminobutyric acid (B) receptor, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, glycine receptor, glutamic acid decarboxylase and paraneoplastic antibodies. The syndrome showed partial spontaneous resolution but 1 year later, typical postencephalopathic features persisted including disinhibition and alteration of sleep–wake cycle. The most likely clinical diagnosis was autoimmune encephalitis and the broader differential diagnoses are discussed within the article. This case demonstrates the need to be aware of this under-recognised and potentially treatable entity. PMID:23112257

  12. The syndrome gelastic seizures-hypothalamic hamartoma: severe, potentially reversible encephalopathy.

    PubMed

    Striano, Salvatore; Striano, Pasquale; Coppola, Antonietta; Romanelli, Pantaleo

    2009-05-01

    Hypothalamic hamartoma (HH) is the pathologic hallmark of a spectrum of epileptic conditions, ranging from a mild form of epilepsy, whose seizures are an urge to laugh without cognitive defects, to the fully developed syndrome of early onset gelastic seizures (GS) associated with precocious puberty and the evolution to a catastrophic epilepsy syndrome. However, a refractory focal or generalized epilepsy develops during the clinical course in nearly all cases. Neurophysiologic and neuroimaging studies have assessed the role of HH in the generation of the GS as well as in the process of secondary epileptogenesis. Electrophysiologic properties of small gamma-aminobutyric acid (GABA)ergic, spontaneously firing neurons might explain the intrinsic epileptogenicity of HH. Surgical ablation of the HH can reverse both epilepsy and encephalopathy. Gamma-knife radiosurgery and image-guided robotic radiosurgery can be useful and safe approaches for treatment, in particular of small HH.

  13. Ionic changes during experimentally induced seizure activity.

    PubMed

    Lux, H D; Heinemann, U

    1978-01-01

    Changes in intra- and extracellular ionic activity and their relation to generation and termination of seizure phenomena can be studied with the help of ion-selective microelectrodes. Transient changes in extracellular potassium activity (aK) of the cortex regularly accompany paroxysmal activity induced by electrical stimulation and pentylenetetrazol injections or occur within active penicillin and aluminum foci. A rise of aK from baseline levels of about 3 mmoles/l up to ceiling levels of 8--12 mmoles/l, followed by subnormal K activity, is typically found during seizure discharge. Extracellular K accumulation during seizures facilitates the spread into extrafocal regions. Ceiling levels of extracellular aK are characterized by pronounced K reabsorption which is probably a limiting mechanism for the rise in extracellular aK. It may be a consequence of a simultaneous rise in intracellular Na activity that an electrogenic Na--K exchange process is involved in the termination of ictal activity. Seizures are also accompanied by significant reductions in extracellular Ca2+ activity (aCa) to as low as 0.7 mmoles/l (resting aCa 1.25 mmoles/l). There is no critical level of lowered aCa at which a seizure ultimately results. However, unlike changes in aK reductions in aCa can precede ictal activity. Thus, a fall of aCa occurs before the onset of paroxysmal periods during cyclical spike driving in a penicillin focus and before seizures induced by pentylenetetrazol. Ca2+-dependent mechanisms may contribute to seizure generation. In addition to changes in aK and aCa, intracellular chloride activity (aCl) can increase during seizure activity, as a result of an impaired chloride extrusion mechanism, which would lead to a reduced efficacy of inhibitory synaptic transmission and, therefore, to facilitation of seizure generation.

  14. Instantaneous frequency based newborn EEG seizure characterisation

    NASA Astrophysics Data System (ADS)

    Mesbah, Mostefa; O'Toole, John M.; Colditz, Paul B.; Boashash, Boualem

    2012-12-01

    The electroencephalogram (EEG), used to noninvasively monitor brain activity, remains the most reliable tool in the diagnosis of neonatal seizures. Due to their nonstationary and multi-component nature, newborn EEG seizures are better represented in the joint time-frequency domain than in either the time domain or the frequency domain. Characterising newborn EEG seizure nonstationarities helps to better understand their time-varying nature and, therefore, allow developing efficient signal processing methods for both modelling and seizure detection and classification. In this article, we used the instantaneous frequency (IF) extracted from a time-frequency distribution to characterise newborn EEG seizures. We fitted four frequency modulated (FM) models to the extracted IFs, namely a linear FM, a piecewise-linear FM, a sinusoidal FM, and a hyperbolic FM. Using a database of 30-s EEG seizure epochs acquired from 35 newborns, we were able to show that, depending on EEG channel, the sinusoidal and piecewise-linear FM models best fitted 80-98% of seizure epochs. To further characterise the EEG seizures, we calculated the mean frequency and frequency span of the extracted IFs. We showed that in the majority of the cases (>95%), the mean frequency resides in the 0.6-3 Hz band with a frequency span of 0.2-1 Hz. In terms of the frequency of occurrence of the four seizure models, the statistical analysis showed that there is no significant difference( p = 0.332) between the two hemispheres. The results also indicate that there is no significant differences between the two hemispheres in terms of the mean frequency ( p = 0.186) and the frequency span ( p = 0.302).

  15. ATPergic signalling during seizures and epilepsy.

    PubMed

    Engel, Tobias; Alves, Mariana; Sheedy, Caroline; Henshall, David C

    2016-05-01

    Much progress has been made over the last few decades in the identification of new anti-epileptic drugs (AEDs). However, 30% of epilepsy patients suffer poor seizure control. This underscores the need to identify alternative druggable neurotransmitter systems and drugs with novel mechanisms of action. An emerging concept is that seizure generation involves a complex interplay between neurons and glial cells at the tripartite synapse and neuroinflammation has been proposed as one of the main drivers of epileptogenesis. The ATP-gated purinergic receptor family is expressed throughout the brain and is functional on neurons and glial cells. ATP is released in high amounts into the extracellular space after increased neuronal activity and during chronic inflammation and cell death to act as a neuro- and gliotransmitter. Emerging work shows pharmacological targeting of ATP-gated purinergic P2 receptors can potently modulate seizure generation, inflammatory processes and seizure-induced brain damage. To date, work showing the functional contribution of P2 receptors has been mainly performed in animal models of acute seizures, in particular, by targeting the ionotropic P2X7 receptor subtype. Other ionotropic P2X and metabotropic P2Y receptor family members have also been implicated in pathological processes following seizures such as the P2X4 receptor and the P2Y12 receptor. However, during epilepsy, the characterization of P2 receptors was mostly restricted to the study of expressional changes of the different receptor subtypes. This review summarizes the work to date on ATP-mediated signalling during seizures and the functional impact of targeting the ATP-gated purinergic receptors on seizures and seizure-induced pathology. This article is part of the Special Issue entitled 'Purines in Neurodegeneration and Neuroregeneration'.

  16. Forebrain neurogenesis after focal Ischemic and traumatic brain injury.

    PubMed

    Kernie, Steven G; Parent, Jack M

    2010-02-01

    Neural stem cells persist in the adult mammalian forebrain and are a potential source of neurons for repair after brain injury. The two main areas of persistent neurogenesis, the subventricular zone (SVZ)-olfactory bulb pathway and hippocampal dentate gyrus, are stimulated by brain insults such as stroke or trauma. Here we focus on the effects of focal cerebral ischemia on SVZ neural progenitor cells in experimental stroke, and the influence of mechanical injury on adult hippocampal neurogenesis in models of traumatic brain injury (TBI). Stroke potently stimulates forebrain SVZ cell proliferation and neurogenesis. SVZ neuroblasts are induced to migrate to the injured striatum, and to a lesser extent to the peri-infarct cortex. Controversy exists as to the types of neurons that are generated in the injured striatum, and whether adult-born neurons contribute to functional restoration remains uncertain. Advances in understanding the regulation of SVZ neurogenesis in general, and stroke-induced neurogenesis in particular, may lead to improved integration and survival of adult-born neurons at sites of injury. Dentate gyrus cell proliferation and neurogenesis similarly increase after experimental TBI. However, pre-existing neuroblasts in the dentate gyrus are vulnerable to traumatic insults, which appear to stimulate neural stem cells in the SGZ to proliferate and replace them, leading to increased numbers of new granule cells. Interventions that stimulate hippocampal neurogenesis appear to improve cognitive recovery after experimental TBI. Transgenic methods to conditionally label or ablate neural stem cells are beginning to further address critical questions regarding underlying mechanisms and functional significance of neurogenesis after stroke or TBI. Future therapies should be aimed at directing appropriate neuronal replacement after ischemic or traumatic injury while suppressing aberrant integration that may contribute to co-morbidities such as epilepsy or

  17. Hippocampal Neuro-Networks and Dendritic Spine Perturbations in Epileptogenesis Are Attenuated by Neuroprotectin D1

    PubMed Central

    Musto, Alberto E.; Walker, Chelsey P.; Petasis, Nicos A.; Bazan, Nicolas G.

    2015-01-01

    Purpose Limbic epileptogenesis triggers molecular and cellular events that foster the establishment of aberrant neuronal networks that, in turn, contribute to temporal lobe epilepsy (TLE). Here we have examined hippocampal neuronal network activities in the pilocarpine post-status epilepticus model of limbic epileptogenesis and asked whether or not the docosahexaenoic acid (DHA)-derived lipid mediator, neuroprotectin D1 (NPD1), modulates epileptogenesis. Methods Status epilepticus (SE) was induced by intraperitoneal administration of pilocarpine in adult male C57BL/6 mice. To evaluate simultaneous hippocampal neuronal networks, local field potentials were recorded from multi-microelectrode arrays (silicon probe) chronically implanted in the dorsal hippocampus. NPD1 (570 μg/kg) or vehicle was administered intraperitoneally daily for five consecutive days 24 hours after termination of SE. Seizures and epileptiform activity were analyzed in freely-moving control and treated mice during epileptogenesis and epileptic periods. Then hippocampal dendritic spines were evaluated using Golgi-staining. Results We found brief spontaneous microepileptiform activity with high amplitudes in the CA1 pyramidal and stratum radiatum in epileptogenesis. These aberrant activities were attenuated following systemic NPD1 administration, with concomitant hippocampal dendritic spine protection. Moreover, NPD1 treatment led to a reduction in spontaneous recurrent seizures. Conclusions Our results indicate that NPD1 displays neuroprotective bioactivity on the hippocampal neuronal network ensemble that mediates aberrant circuit activity during epileptogenesis. Insight into the molecular signaling mediated by neuroprotective bioactivity of NPD1 on neuronal network dysfunction may contribute to the development of anti-epileptogenic therapeutic strategies. PMID:25617763

  18. Biotelemetry system for Epilepsy Seizure Control

    SciTech Connect

    Smith, LaCurtise; Bohnert, George W.

    2009-07-02

    The Biotelemetry System for Epilepsy Seizure Control Project developed and tested an automated telemetry system for use in an epileptic seizure prevention device that precisely controls localized brain temperature. This project was a result of a Department of Energy (DOE) Global Initiatives for Proliferation Prevention (GIPP) grant to the Kansas City Plant (KCP), Argonne National Laboratory (ANL), and Pacific Northwest National Laboratory (PNNL) to partner with Flint Hills Scientific, LLC, Lawrence, KS and Biophysical Laboratory Ltd (BIOFIL), Sarov, Russia to develop a method to help control epileptic seizures.

  19. Hallervorden-Spatz Syndrome with Seizures.

    PubMed

    Gothwal, Sunil; Nayan, Swati

    2016-04-01

    Hallervorden-Spatz syndrome is a disorder characterized by dystonia, parkinsonism, and iron accumulation in the brain. The disease is caused by mutations in gene encoding pantothenate kinase 2 (PANK2) and patients have pantothenate kinase-associated neurodegeneration. We present an 8-year-old boy with progressive muscle dystonia, neuroregression, frequent fall and multiple injury marks of different stages. Seizures are rare with PANK2. This child had seizure onset at 4 years of age and seizure free on valproate and levetricetam. The CT scan showed tiger eye appearance and mutations on PANK2 gene.

  20. Hallervorden–Spatz Syndrome with Seizures

    PubMed Central

    Gothwal, Sunil; Nayan, Swati

    2016-01-01

    Hallervorden-Spatz syndrome is a disorder characterized by dystonia, parkinsonism, and iron accumulation in the brain. The disease is caused by mutations in gene encoding pantothenate kinase 2 (PANK2) and patients have pantothenate kinase-associated neurodegeneration. We present an 8-year-old boy with progressive muscle dystonia, neuroregression, frequent fall and multiple injury marks of different stages. Seizures are rare with PANK2. This child had seizure onset at 4 years of age and seizure free on valproate and levetricetam. The CT scan showed tiger eye appearance and mutations on PANK2 gene. PMID:27303611

  1. Loss of hippocampal interneurons and epileptogenesis: a comparison of two animal models of acquired epilepsy.

    PubMed

    Huusko, Noora; Römer, Christine; Ndode-Ekane, Xavier Ekolle; Lukasiuk, Katarzyna; Pitkänen, Asla

    2015-01-01

    Reduced hippocampal GABAergic inhibition is acknowledged to be associated with epilepsy. However, there are no studies that had quantitatively compared the loss of various interneuron populations in different models of epilepsy. We tested a hypothesis that the more severe the loss of hippocampal interneurons, the more severe was the epilepsy. Epileptogenesis was triggered in adult rats by status epilepticus (SE) (56 SE, 24 controls) or by traumatic brain injury (TBI) (45 TBI, 23 controls). The total number of hippocampal parvalbumin (PARV), cholecystokinin (CCK), calretinin (CR), somatostatin (SOM), or neuropeptide Y (NPY) positive neurons was estimated using unbiased stereology at 1 or 6 months post-insult. The rats with TBI had no spontaneous seizures but showed increased seizure susceptibility. Eleven of the 28 rats (39 %) in the SE group had spontaneous seizures. The most affected hippocampal area after TBI was the ipsilateral dentate gyrus, where 62 % of PARV-immunoreactive (ir) (p < 0.001 compared to controls), 77 % of CR-ir (p < 0.05), 46 % of SOM-ir (p < 0.001), and 59 % of NPY-ir (p < 0.001) cells remained at 1 month after TBI. At 6 months post-TBI, only 35 % of PARV-ir (p < 0.001 compared to controls), 63 % of CCK-ir (p < 0.01), 74 % of CR-ir (p < 0.001), 55 % of SOM-ir (p < 0.001), and 51 % of NPY-ir (p < 0.001) cells were remaining. Moreover, the reduction in PARV-ir, CCK-ir, and CR-ir neurons was bilateral (all p < 0.05). Substantial reductions in different neuronal populations were also found in subfields of the CA3 and CA1. In rats with epilepsy after SE, the number of PARV-ir neurons was reduced in the ipsilateral CA1 (80 % remaining, p < 0.05) and the number of NPY-ir neurons bilaterally in the dentate gyrus (33-37 %, p < 0.01) and the CA3 (54-57 %, p < 0.05). Taken together, interneuron loss was substantially more severe, widespread, progressive, and included more interneuron subclasses after TBI than after SE. Interneurons responsible for

  2. Eight Flurothyl-Induced Generalized Seizures Lead to the Rapid Evolution of Spontaneous Seizures in Mice: A Model of Epileptogenesis with Seizure Remission

    PubMed Central

    Kadiyala, Sridhar B.; Yannix, Joshua Q.; Nalwalk, Julia W.; Papandrea, Dominick; Beyer, Barbara S.; Herron, Bruce J.

    2016-01-01

    The occurrence of recurrent, unprovoked seizures is the hallmark of human epilepsy. Currently, only two-thirds of this patient population has adequate seizure control. New epilepsy models provide the potential for not only understanding the development of spontaneous seizures, but also for testing new strategies to treat this disorder. Here, we characterize a primary generalized seizure model of epilepsy following repeated exposure to the GABAA receptor antagonist, flurothyl, in which mice develop spontaneous seizures that remit within 1 month. In this model, we expose C57BL/6J mice to flurothyl until they experience a generalized seizure. Each of these generalized seizures typically lasts <30 s. We induce one seizure per day for 8 d followed by 24 h video-electroencephalographic recordings. Within 1 d following the last of eight flurothyl-induced seizures, ∼50% of mice have spontaneous seizures. Ninety-five percent of mice tested have seizures within the first week of the recording period. Of the spontaneous seizures recorded, the majority are generalized clonic seizures, with the remaining 7–12% comprising generalized clonic seizures that transition into brainstem seizures. Over the course of an 8 week recording period, spontaneous seizure episodes remit after ∼4 weeks. Overall, the repeated flurothyl paradigm is a model of epileptogenesis with spontaneous seizures that remit. This model provides an additional tool in our armamentarium for understanding the mechanisms underlying epileptogenesis and may provide insights into why spontaneous seizures remit without anticonvulsant treatment. Elucidating these processes could lead to the development of new epilepsy therapeutics. SIGNIFICANCE STATEMENT Epilepsy is a chronic disorder characterized by the occurrence of recurrent, unprovoked seizures in which the individual seizure–ictal events are self-limiting. Remission of recurrent, unprovoked seizures can be achieved in two-thirds of cases by treatment with

  3. Statistical earthquake focal mechanism forecasts

    NASA Astrophysics Data System (ADS)

    Kagan, Yan Y.; Jackson, David D.

    2014-04-01

    Forecasts of the focal mechanisms of future shallow (depth 0-70 km) earthquakes are important for seismic hazard estimates and Coulomb stress, and other models of earthquake occurrence. Here we report on a high-resolution global forecast of earthquake rate density as a function of location, magnitude and focal mechanism. In previous publications we reported forecasts of 0.5° spatial resolution, covering the latitude range from -75° to +75°, based on the Global Central Moment Tensor earthquake catalogue. In the new forecasts we have improved the spatial resolution to 0.1° and the latitude range from pole to pole. Our focal mechanism estimates require distance-weighted combinations of observed focal mechanisms within 1000 km of each gridpoint. Simultaneously, we calculate an average rotation angle between the forecasted mechanism and all the surrounding mechanisms, using the method of Kagan & Jackson proposed in 1994. This average angle reveals the level of tectonic complexity of a region and indicates the accuracy of the prediction. The procedure becomes problematical where longitude lines are not approximately parallel, and where shallow earthquakes are so sparse that an adequate sample spans very large distances. North or south of 75°, the azimuths of points 1000 km away may vary by about 35°. We solved this problem by calculating focal mechanisms on a plane tangent to the Earth's surface at each forecast point, correcting for the rotation of the longitude lines at the locations of earthquakes included in the averaging. The corrections are negligible between -30° and +30° latitude, but outside that band uncorrected rotations can be significantly off. Improved forecasts at 0.5° and 0.1° resolution are posted at http://eq.ess.ucla.edu/kagan/glob_gcmt_index.html.

  4. Posttraumatic seizures and epilepsy in adult rats after controlled cortical impact.

    PubMed

    Kelly, Kevin M; Miller, Eric R; Lepsveridze, Eka; Kharlamov, Elena A; Mchedlishvili, Zakaria

    2015-11-01

    Posttraumatic epilepsy (PTE) has been modeled with different techniques of experimental traumatic brain injury (TBI) using mice and rats at various ages. We hypothesized that the technique of controlled cortical impact (CCI) could be used to establish a model of PTE in young adult rats. A total of 156 male Sprague-Dawley rats of 2-3 months of age (128 CCI-injured and 28 controls) was used for monitoring and/or anatomical studies. Provoked class 3-5 seizures were recorded by video monitoring in 7/57 (12.3%) animals in the week immediately following CCI of the right parietal cortex; none of the 7 animals demonstrated subsequent spontaneous convulsive seizures. Monitoring with video and/or video-EEG was performed on 128 animals at various time points 8-619 days beyond one week following CCI during which 26 (20.3%) demonstrated nonconvulsive or convulsive epileptic seizures. Nonconvulsive epileptic seizures of >10s were demonstrated in 7/40 (17.5%) animals implanted with 2 or 3 depth electrodes and usually characterized by an initial change in behavior (head raising or animal alerting) followed by motor arrest during an ictal discharge that consisted of high-amplitude spikes or spike-waves with frequencies ranging between 1 and 2Hz class 3-5 epileptic seizures were recorded by video monitoring in 17/88 (19%) and by video-EEG in 2/40 (5%) CCI-injured animals. Ninety of 156 (58%) animals (79 CCI-injured, 13 controls) underwent transcardial perfusion for gross and microscopic studies. CCI caused severe brain tissue loss and cavitation of the ipsilateral cerebral hemisphere associated with cell loss in the hippocampal CA1 and CA3 regions, hilus, and dentate granule cells, and thalamus. All Timm-stained CCI-injured brains demonstrated ipsilateral hippocampal mossy fiber sprouting in the inner molecular layer. These results indicate that the CCI model of TBI in adult rats can be used to study the structure-function relationships that underlie epileptogenesis and PTE.

  5. Traumatic alterations in GABA signaling disrupt hippocampal network activity in the developing brain

    PubMed Central

    Dzhala, Volodymyr; Valeeva, Guzel; Glykys, Joseph; Khazipov, Rustem; Staley, Kevin

    2012-01-01

    Severe head trauma causes widespread neuronal shear injuries and acute seizures. Shearing of neural processes might contribute to seizures by disrupting the transmembrane ion gradients that subserve normal synaptic signaling. To test this possibility, we investigated changes in intracellular chloride concentration ([Cl−]i) associated with the widespread neural shear injury induced during preparation of acute brain slices. In hippocampal slices and intact hippocampal preparations from immature CLM-1 mice, increases in [Cl−]i correlated with disruption of neural processes and biomarkers of cell injury. Traumatized neurons with higher [Cl−]i demonstrated excitatory GABA signaling, remained synaptically active, and facilitated network activity as assayed by the frequency of extracellular action potentials and spontaneous network-driven oscillations. These data support a more inhibitory role for GABA in the unperturbed immature brain, demonstrate the utility of the acute brain slice preparation for the study of the consequences of trauma, and provide potential mechanisms for both GABA-mediated excitatory network events in the slice preparation and early post-traumatic seizures. PMID:22442068

  6. Profound suppression of kindled seizures by cysteamine: possible role of somatostatin to kindled seizures.

    PubMed

    Higuchi, T; Sikand, G S; Kato, N; Wada, J A; Friesen, H G

    1983-12-12

    Recently we reported significant increase in immunoreactive somatostatin content in various brain regions of amygdaloid-kindled rats. We report here that acute intraperitoneal administration of cysteamine, an agent reported to deplete brain and gastrointestinal immunoreactive somatostatin content in kindled rats, led to profound suppression of kindled seizures. Purified anti-somatostatin antibody injected intracerebroventricularly also blocked the kindled seizures. The results show that endogenous immunoreactive somatostatin has a role in the development of seizures in amygdaloid kindled rats.

  7. Seizure-induced plasticity of h channels in entorhinal cortical layer III pyramidal neurons.

    PubMed

    Shah, Mala M; Anderson, Anne E; Leung, Victor; Lin, Xiaodi; Johnston, Daniel

    2004-10-28

    The entorhinal cortex (EC) provides the predominant excitatory drive to the hippocampal CA1 and subicular neurons in chronic epilepsy. Discerning the mechanisms underlying signal integration within EC neurons is essential for understanding network excitability alterations involving the hippocampus during epilepsy. Twenty-four hours following a single seizure episode when there were no behavioral or electrographic seizures, we found enhanced spontaneous activity still present in the rat EC in vivo and in vitro. The increased excitability was accompanied by a profound reduction in I(h) in EC layer III neurons and a significant decline in HCN1 and HCN2 subunits that encode for h channels. Consequently, dendritic excitability was enhanced, resulting in increased neuronal firing despite hyperpolarized membrane potentials. The loss of I(h) and the increased neuronal excitability persisted for 1 week following seizures. Our results suggest that dendritic I(h) plays an important role in determining the excitability of EC layer III neurons and their associated neural networks.

  8. [Research advances in circadian rhythm of epileptic seizures].

    PubMed

    Yang, Wen-Qi; Li, Hong

    2017-01-01

    The time phase of epileptic seizures has attracted more and more attention. Epileptic seizures have their own circadian rhythm. The same type of epilepsy has different seizure frequencies in different time periods and states (such as sleeping/awakening state and natural day/night cycle). The circadian rhythm of epileptic seizures has complex molecular and endocrine mechanisms, and currently there are several hypotheses. Clarification of the circadian rhythm of epileptic seizures and prevention and administration according to such circadian rhythm can effectively control seizures and reduce the adverse effects of drugs. The research on the circadian rhythm of epileptic seizures provides a new idea for the treatment of epilepsy.

  9. Increasing Epilepsy Awareness in Schools: A Seizure Smart Schools Project.

    PubMed

    Brook, Heather A; Hiltz, Cynthia M; Kopplin, Vicki L; Lindeke, Linda L

    2015-08-01

    A high prevalence of epilepsy diagnoses and seizure events among students was identified at a large Midwestern school district. In partnership with the Epilepsy Foundation of Minnesota (EFMN), a quality improvement project was conducted to provide education and resources to staff caring for school children with seizures. School nurses (N = 26) were trained as seizure management educators and instructed staff in 21 schools on seizure awareness and response. School nurses utilized new seizure management resources, a procedural guideline, and care plan updates. The majority of school nurses rated the resources and training interventions as "very helpful." School nurse confidence in managing students with seizures increased, seizure action plan use increased, and 88% of children's records with new seizure diagnoses had completed documentation. School nurses played vital roles in increasing seizure awareness as educators and care managers. EFMN is using this project as an exemplar for expanding its Seizure Smart Schools program.

  10. What is the importance of abnormal "background" activity in seizure generation?

    PubMed

    Staba, Richard J; Worrell, Gregory A

    2014-01-01

    Investigations of interictal epileptiform spikes and seizures have played a central role in the study of epilepsy. The background EEG activity, however, has received less attention. In this chapter we discuss the characteristic features of the background activity of the brain when individuals are at rest and awake (resting wake) and during sleep. The characteristic rhythms of the background EEG are presented, and the presence of 1/f (β) behavior of the EEG power spectral density is discussed and its possible origin and functional significance. The interictal EEG findings of focal epilepsy and the impact of interictal epileptiform spikes on cognition are also discussed.

  11. Automatic Detection of Seizures with Applications

    NASA Technical Reports Server (NTRS)

    Olsen, Dale E.; Harris, John C.; Cutchis, Protagoras N.; Cristion, John A.; Lesser, Ronald P.; Webber, W. Robert S.

    1993-01-01

    There are an estimated two million people with epilepsy in the United States. Many of these people do not respond to anti-epileptic drug therapy. Two devices can be developed to assist in the treatment of epilepsy. The first is a microcomputer-based system designed to process massive amounts of electroencephalogram (EEG) data collected during long-term monitoring of patients for the purpose of diagnosing seizures, assessing the effectiveness of medical therapy, or selecting patients for epilepsy surgery. Such a device would select and display important EEG events. Currently many such events are missed. A second device could be implanted and would detect seizures and initiate therapy. Both of these devices require a reliable seizure detection algorithm. A new algorithm is described. It is believed to represent an improvement over existing seizure detection algorithms because better signal features were selected and better standardization methods were used.

  12. Hippocampal neurogenesis: Learning to remember.

    PubMed

    Lazarov, Orly; Hollands, Carolyn

    2016-01-01

    Alzheimer's disease, the most prevalent form of dementia in the elderly, is characterized by progressive memory loss and cognitive dysfunction. It has become increasingly clear that while neuronal cell loss in the entorhinal cortex and hippocampus occurs in Alzheimer's disease, it is preceded by a long period of deficits in the connectivity of the hippocampal formation that contributes to the vulnerability of these circuits. Hippocampal neurogenesis plays a role in the maintenance and function of the dentate gyrus and hippocampal circuitry. This review will examine the evidence suggesting that hippocampal neurogenesis plays a role in cognitive function that is affected in Alzheimer's disease, will discuss the cognitive assessments used for the detection of Alzheimer's disease in humans and rodent models of familial Alzheimer's disease, and their value for unraveling the mechanism underlying the development of cognitive impairments and dementia.

  13. Commercialization of Seizure Prediction Technology Promises and Pitfalls of Biosignal Analysis: Seizure Prediction and Management (A case study);

    DTIC Science & Technology

    2007-11-02

    biosignals utilizing computationally intensive algorithms are useful and provide no limitation for clinical Commercialization of Seizure Prediction...Technology Promises and Pitfalls of Biosignal Analysis: Seizure Prediction and Management (A case study); Mark T. Rise, Ph.D. Technical Fellow...Title and Subtitle Commercialization of Seizure Prediction Technology Promises and Pitfalls of Biosignal Analysis: Seizure Prediction and

  14. CADASIL Initially Presented with a Seizure

    PubMed Central

    Oh, Jung-Hwan; Kang, Bong Su; Choi, Jay Chol

    2016-01-01

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary disease of the cerebral small blood vessels characterized by recurrent ischemic strokes, migraine, and progressive cognitive impairment. In patients with CADASIL, in whom subcortical white matter structures are typically involved, epileptic seizures have been rarely reported as an initial clinical symptom. We describe a patient genetically confirmed as having CADASIL who initially presented with a seizure. PMID:28101484

  15. Acute provoked reflex seizures induced by thinking.

    PubMed

    Nevler, Naomi; Gandelman-Marton, Revital

    2012-11-01

    Thinking epilepsy is a rare form of reflex epilepsy that can be induced by specific cognitive tasks, and occurs mainly in idiopathic generalized epilepsies. We report a case of complex partial seizures triggered by thinking in a young man with acute bacterial meningitis and a remote head injury. This case illustrates that thinking-induced reflex seizures can be partial and can be provoked by an acute brain insult.

  16. Sheehan's syndrome presenting as postpartum seizures.

    PubMed

    Jain, G; Singh, D; Kumar, S

    2010-05-01

    We report a case where a patient presented with generalised tonic-clonic seizures secondary to nausea, vomiting and dehydration. She had suffered a postpartum haemorrhage six months previously. On laboratory assessment hyponatraemia and low hormone concentrations suggested pituitary failure. The diagnosis was confirmed by magnetic resonance imaging of the head, which showed a partially empty sella turcica. Given the severity of the morbidity in this case we emphasise that Sheehan's syndrome should be suspected in women presenting with postpartum seizures.

  17. Successful surgery in lesional epilepsy secondary to posterior quandrant ulegyria coexisting with benign childhood focal epilepsy: A case report.

    PubMed

    Wang, Fengpeng; Zheng, Honghua; Zhang, Xiaobin; Li, Yanfang; Gao, Zhiying; Wang, Yuanqing; Liu, Xiaowei; Yao, Yi

    2016-10-01

    The present study reports, for the first time, a rare case of benign childhood focal epilepsy(BCFE) coexisting with lesional epilepsy secondary to parietooccipital ulegyria. The patient underwent right parietooccipital lobe disconnection plus tailored resection of temporooccipitoparietal junction cortex under electrocorticography (ECoG) monitoring. Post-operatively, there was no impairment of neurological function and the patient only experiences a few breakthrough benign partial seizures during sleep.

  18. A critical review of the different conceptual hypotheses framing human focal epilepsy.

    PubMed

    Nair, Dileep R; Mohamed, Armin; Burgess, Richard; Lüders, Hans

    2004-06-01

    In the attempt to understand the processes affecting human focal epilepsy, various models that have been proposed as a back drop to which current observations of the clinical manifestations and therapies in this disorder can be tested. There are three main models that are reviewed. The notion of epileptogenicity as described by Penfield and Jasper's epileptogenic zone model postulates that specific regions of cerebral cortex have varying degrees of importance in the generation of focal epilepsy. A variation of this hypothesis comprises the second model put forth by Talairach and Bancaud. In this view the notion of the epileptogenic zone is expanded to incorporate a larger regions of cerebral cortex involved in the seizure propagation. A third concept and more separate hypothesis suggests that all components of the neural network involved in focal epilepsy are equally importance in the initiation and maintenance of the seizure. The various concepts underlying these models are reviewed in this paper and data from clinical and neurophysiologic observations are discussed in the context of these models. We suggest in this paper that the data best supports the epileptogenic zone hypothesis put forth by Penfield and Jasper.

  19. Relationship of EEG sources of neonatal seizures to acute perinatal brain lesions seen on MRI: a pilot study.

    PubMed

    Despotovic, Ivana; Cherian, Perumpillichira J; De Vos, Maarten; Hallez, Hans; Deburchgraeve, Wouter; Govaert, Paul; Lequin, Maarten; Visser, Gerhard H; Swarte, Renate M; Vansteenkiste, Ewout; Van Huffel, Sabine; Philips, Wilfried

    2013-10-01

    Even though it is known that neonatal seizures are associated with acute brain lesions, the relationship of electroencephalographic (EEG) seizures to acute perinatal brain lesions visible on magnetic resonance imaging (MRI) has not been objectively studied. EEG source localization is successfully used for this purpose in adults, but it has not been sufficiently explored in neonates. Therefore, we developed an integrated method for ictal EEG dipole source localization based on a realistic head model to investigate the utility of EEG source imaging in neonates with postasphyxial seizures. We describe here our method and compare the dipole seizure localization results with acute perinatal lesions seen on brain MRI in 10 full-term infants with neonatal encephalopathy. Through experimental studies, we also explore the sensitivity of our method to the electrode positioning errors and the variations in neonatal skull geometry and conductivity. The localization results of 45 focal seizures from 10 neonates are compared with the visual analysis of EEG and MRI data, scored by expert physicians. In 9 of 10 neonates, dipole locations showed good relationship with MRI lesions and clinical data. Our experimental results also suggest that the variations in the used values for skull conductivity or thickness have little effect on the dipole localization, whereas inaccurate electrode positioning can reduce the accuracy of source estimates. The performance of our fused method indicates that ictal EEG source imaging is feasible in neonates and with further validation studies, this technique can become a useful diagnostic tool.

  20. A testbed to explore the optimal electrical stimulation parameters for suppressing inter-ictal spikes in human hippocampal slices.

    PubMed

    Min-Chi Hsiao; Pen-Ning Yu; Dong Song; Liu, Charles Y; Heck, Christi N; Millett, David; Berger, Theodore W

    2014-01-01

    New interventions using neuromodulatory devices such as vagus nerve stimulation, deep brain stimulation and responsive neurostimulation are available or under study for the treatment of refractory epilepsy. Since the actual mechanisms of the onset and termination of the seizure are still unclear, most researchers or clinicians determine the optimal stimulation parameters through trial-and-error procedures. It is necessary to further explore what types of electrical stimulation parameters (these may include stimulation frequency, amplitude, duration, interval pattern, and location) constitute a set of optimal stimulation paradigms to suppress seizures. In a previous study, we developed an in vitro epilepsy model using hippocampal slices from patients suffering from mesial temporal lobe epilepsy. Using a planar multi-electrode array system, inter-ictal activity from human hippocampal slices was consistently recorded. In this study, we have further transferred this in vitro seizure model to a testbed for exploring the possible neurostimulation paradigms to inhibit inter-ictal spikes. The methodology used to collect the electrophysiological data, the approach to apply different electrical stimulation parameters to the slices are provided in this paper. The results show that this experimental testbed will provide a platform for testing the optimal stimulation parameters of seizure cessation. We expect this testbed will expedite the process for identifying the most effective parameters, and may ultimately be used to guide programming of new stimulating paradigms for neuromodulatory devices.

  1. Acute Symptomatic Seizures Caused by Electrolyte Disturbances.

    PubMed

    Nardone, Raffaele; Brigo, Francesco; Trinka, Eugen

    2016-01-01

    In this narrative review we focus on acute symptomatic seizures occurring in subjects with electrolyte disturbances. Quite surprisingly, despite its clinical relevance, this issue has received very little attention in the scientific literature. Electrolyte abnormalities are commonly encountered in clinical daily practice, and their diagnosis relies on routine laboratory findings. Acute and severe electrolyte imbalances can manifest with seizures, which may be the sole presenting symptom. Seizures are more frequently observed in patients with sodium disorders (especially hyponatremia), hypocalcemia, and hypomagnesemia. They do not entail a diagnosis of epilepsy, but are classified as acute symptomatic seizures. EEG has little specificity in differentiating between various electrolyte disturbances. The prominent EEG feature is slowing of the normal background activity, although other EEG findings, including various epileptiform abnormalities may occur. An accurate and prompt diagnosis should be established for a successful management of seizures, as rapid identification and correction of the underlying electrolyte disturbance (rather than an antiepileptic treatment) are of crucial importance in the control of seizures and prevention of permanent brain damage.

  2. Acute Symptomatic Seizures Caused by Electrolyte Disturbances

    PubMed Central

    Nardone, Raffaele; Brigo, Francesco

    2016-01-01

    In this narrative review we focus on acute symptomatic seizures occurring in subjects with electrolyte disturbances. Quite surprisingly, despite its clinical relevance, this issue has received very little attention in the scientific literature. Electrolyte abnormalities are commonly encountered in clinical daily practice, and their diagnosis relies on routine laboratory findings. Acute and severe electrolyte imbalances can manifest with seizures, which may be the sole presenting symptom. Seizures are more frequently observed in patients with sodium disorders (especially hyponatremia), hypocalcemia, and hypomagnesemia. They do not entail a diagnosis of epilepsy, but are classified as acute symptomatic seizures. EEG has little specificity in differentiating between various electrolyte disturbances. The prominent EEG feature is slowing of the normal background activity, although other EEG findings, including various epileptiform abnormalities may occur. An accurate and prompt diagnosis should be established for a successful management of seizures, as rapid identification and correction of the underlying electrolyte disturbance (rather than an antiepileptic treatment) are of crucial importance in the control of seizures and prevention of permanent brain damage. PMID:26754778

  3. Monitor for status epilepticus seizures

    NASA Technical Reports Server (NTRS)

    Johnson, Mark; Simkins, Thomas

    1994-01-01

    This paper describes the sensor technology and associated electronics of a monitor designed to detect the onset of a seizure disorder called status epilepticus. It is a condition that affects approximately 3-5 percent of those individuals suffering from epilepsy. This form of epilepsy does not follow the typical cycle of start-peak-end. The convulsions continue until medically interrupted and are life threatening. The mortality rate is high without prompt medical treatment at a suitable facility. The paper describes the details of a monitor design that provides an inexpensive solution to the needs of those responsible for the care of individuals afflicted with this disorder. The monitor has been designed as a cooperative research and development effort involving the United States Army Armament Research, Development, and Engineering Center's Benet Laboratories (Benet) and the Cerebral Palsy Center for the Disabled (Center), in association with the Department of Neurology at Albany Medical College (AMC). Benet has delivered a working prototype of the device for field testing, in collaboration with Albany Medical College. The Center has identified several children in need of special monitoring and has agreed to pursue commercialization of the device.

  4. Is complete seizure control imperative?

    PubMed

    Andermann, Frederick

    2002-01-01

    Is complete control imperative? The answer depends on whether complete control is indeed possible, on the possibility of achieving modifications of lifestyle, and on the type of epilepsy, with particular reference to the presence of progressive dysfunction. This may be seen in patients with temporal lobe or other forms of focal epilepsy, in the epileptic encephalopathies such as West and Lennox Gastaut Syndromes and even in some patients with idiopathic generalized epilepsy. Progressive memory changes and global cognitive problems are examples. Progressive language deterioration, secondary epileptogenesis and phenomena analogous to kindling are also important issues. How long treatment should be continued depends on many factors, not least the preference of the patient and of the family. Weighing the benefits of complete control versus the side effects and risks of medication or surgery is crucial. There are obvious benefits to complete control; it is imperative if these benefits are greater than the cost.

  5. Increased segregation of brain networks in focal epilepsy: An fMRI graph theory finding.

    PubMed

    Pedersen, Mangor; Omidvarnia, Amir H; Walz, Jennifer M; Jackson, Graeme D

    2015-01-01

    Focal epilepsy is conceived of as activating local areas of the brain as well as engaging regional brain networks. Graph theory represents a powerful quantitative framework for investigation of brain networks. Here we investigate whether functional network changes are present in extratemporal focal epilepsy. Task-free functional magnetic resonance imaging data from 15 subjects with extratemporal epilepsy and 26 age and gender matched healthy controls were used for analysis. Local network properties were calculated using local efficiency, clustering coefficient and modularity metrics. Global network properties were assessed with global efficiency and betweenness centrality metrics. Cost-efficiency of the networks at both local and global levels was evaluated by estimating the physical distance between functionally connected nodes, in addition to the overall numbers of connections in the network. Clustering coefficient, local efficiency and modularity were significantly higher in individuals with focal epilepsy than healthy control subjects, while global efficiency and betweenness centrality were not significantly different between the two groups. Local network properties were also highly efficient, at low cost, in focal epilepsy subjects compared to healthy controls. Our results show that functional networks in focal epilepsy are altered in a way that the nodes of the network are more isolated. We postulate that network regularity, or segregation of the nodes of the networks, may be an adaptation that inhibits the conversion of the interictal state to seizures. It remains possible that this may be part of the epileptogenic process or an effect of medications.

  6. Early Onset of Hypersynchronous Network Activity and Expression of a Marker of Chronic Seizures in the Tg2576 Mouse Model of Alzheimer’s Disease

    PubMed Central

    Bezzina, Charlotte; Verret, Laure; Juan, Cécile; Remaud, Jessica; Halley, Hélène

    2015-01-01

    Cortical and hippocampal hypersynchrony of neuronal networks seems to be an early event in Alzheimer’s disease pathogenesis. Many mouse models of the disease also present neuronal network hypersynchrony, as evidenced by higher susceptibility to pharmacologically-induced seizures, electroencephalographic seizures accompanied by spontaneous interictal spikes and expression of markers of chronic seizures such as neuropeptide Y ectopic expression in mossy fibers. This network hypersynchrony is thought to contribute to memory deficits, but whether it precedes the onset of memory deficits or not in mouse models remains unknown. The earliest memory impairments in the Tg2576 mouse model of Alzheimer’s disease have been observed at 3 months of age. We thus assessed network hypersynchrony in Tg2576 and non-transgenic male mice at 1.5, 3 and 6 months of age. As soon as 1.5 months of age, Tg2576 mice presented higher seizure susceptibility to systemic injection of a GABAA receptor antagonist. They also displayed spontaneous interictal spikes on EEG recordings. Some Tg2576 mice presented hippocampal ectopic expression of neuropeptide Y which incidence seems to increase with age among the Tg2576 population. Our data reveal that network hypersynchrony appears very early in Tg2576 mice, before any demonstrated memory impairments. PMID:25768013

  7. Two-year real-world experience with perampanel in patients with refractory focal epilepsy: Austrian data

    PubMed Central

    Rohracher, Alexandra; Kalss, Gudrun; Leitinger, Markus; Granbichler, Claudia; Deak, Ildiko; Dobesberger, Judith; Kuchukhidze, Giorgi; Thomschewski, Aljoscha; Höfler, Julia; Trinka, Eugen

    2016-01-01

    Background: The aim of this study was to analyse registry data of seizure outcome and adverse events (AEs) for perampanel as add-on therapy in patients with focal epilepsy since its approval in 2012 for adjunctive treatment of focal epilepsy in patients ⩾12 years. Method: A retrospective 2-year chart review of all patients receiving perampanel was carried out. Results: A total of 122 patients received perampanel [median treatment length: 20.1 (range: 3.4–26.8) months]; 71 (58%) remained on treatment at last follow up. Overall, 33 patients (27%) were seizure-free for ⩾3 months at last follow up; of these, eight were seizure free for ⩾3 times the longest interictal interval before perampanel therapy; 18 (15%) had reduced seizure frequency ⩾50%. A total of 58 (47%) had an AE and 34 (28%) withdrew from treatment because of AEs. AEs included dizziness (33%), fatigue (12%), psychiatric symptoms (8%), cognitive deficits (7%), speech problems (5%), nausea (4%) and gait problems (4%). AEs subsided in 17/18 patients (94%) following a 2 mg dose reduction. A total of 43 (35%) took a concomitant enzyme inducer. Patients not taking enzyme inducers were more likely to be seizure free (p = 0.002); there were no other between-group differences. Conclusions: Perampanel was well tolerated and improved seizure control in 42% of patients (50– 100% reduction), with higher rates in those not receiving a concomitant enzyme inducer. AEs, particularly dizziness, were common but often disappeared with a slight dose reduction. The results are consistent with those from randomized controlled trials. PMID:27800020

  8. Variable focal length deformable mirror

    DOEpatents

    Headley, Daniel; Ramsey, Marc; Schwarz, Jens

    2007-06-12

    A variable focal length deformable mirror has an inner ring and an outer ring that simply support and push axially on opposite sides of a mirror plate. The resulting variable clamping force deforms the mirror plate to provide a parabolic mirror shape. The rings are parallel planar sections of a single paraboloid and can provide an on-axis focus, if the rings are circular, or an off-axis focus, if the rings are elliptical. The focal length of the deformable mirror can be varied by changing the variable clamping force. The deformable mirror can generally be used in any application requiring the focusing or defocusing of light, including with both coherent and incoherent light sources.

  9. Focal hyperhidrosis: diagnosis and management

    PubMed Central

    Haider, Aamir; Solish, Nowell

    2005-01-01

    HYPERHIDROSIS, A CONDITION CHARACTERIZED by excessive sweating, can be generalized or focal. Generalized hyperhidrosis involves the entire body and is usually part of an underlying condition, most often an infectious, endocrine or neurologic disorder. Focal hyperhidrosis is idiopathic, occurring in otherwise healthy people. It affects 1 or more body areas, most often the palms, armpits, soles or face. Almost 3% of the general population, largely people aged between 25 and 64 years, experience hyperhidrosis. The condition carries a substantial psychological and social burden, since it interferes with daily activities. However, patients rarely seek a physician's help because many are unaware that they have a treatable medical disorder. Early detection and management of hyperhidrosis can significantly improve a patient's quality of life. There are various topical, systemic, surgical and nonsurgical treatments available with efficacy rates greater than 90%–95%. PMID:15632408

  10. Preictal dynamics of EEG complexity in intracranially recorded epileptic seizure: a case report.

    PubMed

    Bob, Petr; Roman, Robert; Svetlak, Miroslav; Kukleta, Miloslav; Chladek, Jan; Brazdil, Milan

    2014-11-01

    Recent findings suggest that neural complexity reflecting a number of independent processes in the brain may characterize typical changes during epileptic seizures and may enable to describe preictal dynamics. With respect to previously reported findings suggesting specific changes in neural complexity during preictal period, we have used measure of pointwise correlation dimension (PD2) as a sensitive indicator of nonstationary changes in complexity of the electroencephalogram (EEG) signal. Although this measure of complexity in epileptic patients was previously reported by Feucht et al (Applications of correlation dimension and pointwise dimension for non-linear topographical analysis of focal onset seizures. Med Biol Comput. 1999;37:208-217), it was not used to study changes in preictal dynamics. With this aim to study preictal changes of EEG complexity, we have examined signals from 11 multicontact depth (intracerebral) EEG electrodes located in 108 cortical and subcortical brain sites, and from 3 scalp EEG electrodes in a patient with intractable epilepsy, who underwent preoperative evaluation before epilepsy surgery. From those 108 EEG contacts, records related to 44 electrode contacts implanted into lesional structures and white matter were not included into the experimental analysis.The results show that in comparison to interictal period (at about 8-6 minutes before seizure onset), there was a statistically significant decrease in PD2 complexity in the preictal period at about 2 minutes before seizure onset in all 64 intracranial channels localized in various brain sites that were included into the analysis and in 3 scalp EEG channels as well. Presented results suggest that using PD2 in EEG analysis may have significant implications for research of preictal dynamics and prediction of epileptic seizures.

  11. Stigmatic flat focal field spectrograph

    NASA Astrophysics Data System (ADS)

    Niemczyk, T. M.; Gobeli, G. W.

    Advances in two dimensional detectors have created a need for a spectrograph that can produce high fidelity images. Aberrations that detract from image quality in conventional spectrographs are discussed. Ray trace and experimental results obtained for a unique spectrograph designed for use with array detectors, i.e., designed to produce high fidelity images, are presented. The spectrograph employs toroidal mirrors to achieve stigmatic imaging in a flat focal field.

  12. Almost Unilateral Focal Dermal Hypoplasia

    PubMed Central

    Lee, Solam; Choe, Sung Jay

    2017-01-01

    Focal dermal hypoplasia, caused by mutations in PORCN, is an X-linked ectodermal dysplasia, also known as Goltz syndrome. Only seven cases of unilateral or almost unilateral focal dermal hypoplasia have been reported in the English literature and there have been no previously reported cases in the Republic of Korea. A 19-year-old female presented with scalp defects, skin lesions on the right leg and the right trunk, and syndactyly of the right fourth and fifth toes. Cutaneous examination revealed multiple atrophic plaques and a brown and yellow mass with fat herniation and telangiectasia that was mostly located on the lower right leg. She had syndactyly on the right foot and the scalp lesion appeared to be an atrophic, membranous, fibrotic alopecic scar. A biopsy of the calf revealed upper dermal extension of fat cells, dermal atrophy, and loss of dermal collagen. A diagnosis of almost unilateral focal dermal hypoplasia was made on the basis of physical and histologic findings. Henceforth, the patient was referred to a plastic surgeon and an orthopedics department to repair her syndactyly. PMID:28223754

  13. Persistent Focal Behavior and Physical Activity Performance

    ERIC Educational Resources Information Center

    Erfle, Stephen E.

    2014-01-01

    This article examines the proclivity and performance attributes of focal students across time and activities using data from 9,345 students. Three systematic focal behavior partitions are exa