Effects of low-frequency electrical stimulation of the anterior piriform cortex on kainate-induced seizures in rats

ObjectiveRecent evidence in animals and humans suggests that low-frequency stimulation (LFS) has significant antiepileptic properties. The anterior piriform cortex (APC) is a highly susceptible seizure-trigger zone and may be critical for the initiation and propagation of seizures originating from cortical and limbic foci.We used the kainic acid (KA) seizure model in rats to assess the therapeutic effect of LFS of the APC on seizures.MethodsAdult male Sprague–Dawley rats were implanted with electrodes in the left APC and recording electrodes bilaterally in the hippocampal CA3 regions. Rats were monitored continuously with video-EEG after the emergence of spontaneous recurrent seizures that followed induction of status epilepticus by intraperitoneal KA. After two weeks of baseline recordings to determine seizure frequency, LFS of the APC was applied 60-min On 15-min Off, for two weeks with 1 Hz biphasic square waves, 0.2 ms pulse width, at 200 μA. Another 2-week period of video-EEG monitoring was done after the cessation of LFS to study the carry-over effect. Changes in seizure frequency, severity, and duration between baseline, during LFS, and post-LFS were analyzed using the Poisson regression model.ResultsOverall seizure frequency decreased during the post-LFS period to 5% of that at baseline (p = 0.003). Severe seizures (stages 4 and 5 on the Racine scale) decreased to 0% of the baseline during the post-LFS period.ConclusionsTwo weeks of LFS of the APC reduced spontaneous seizure frequency and severity in the KA model with the effect outlasting the stimulation. Our findings suggest that the APC can be an important therapeutic target for stimulation in epilepsy.     

Seizure suppression by EEG-guided repetitive transcranial magnetic stimulation in the rat

ObjectiveTo test the anticonvulsive potential of a range of repetitive transcranial magnetic stimulation (rTMS) frequencies by novel methods for simultaneous EEG and rTMS in a rat seizure model.MethodsSeizures were triggered by intraperitoneal kainic acid (KA; 10 mg/kg). Rats (n = 21) were divided into three groups in which individual seizures were treated with rTMS trains at one of three frequencies: 0.25, 0.5 or 0.75 Hz. EEG was continuously viewed by an operator who identified each seizure onset. Consecutive seizures in each animal were (1) treated with active rTMS, (2) treated with sham rTMS, or (3) were untreated. EEG was re-analyzed post hoc by visual inspection, and seizure durations were compared within and between treatment groups.ResultsKA-induced seizures were abbreviated by 0.75 Hz (P = 0.019) and 0.5 Hz (P = 0.033) active EEG-guided rTMS. In contrast, neither active 0.25 Hz rTMS nor the control conditions affected seizure duration (P > 0.2).ConclusionsWe demonstrate that EEG-guided rTMS can suppress seizures in the rat KA epilepsy model, and that the effect is frequency dependent, with 0.75 and 0.5 Hz rTMS being superior to 0.25 Hz rTMS.SignificanceThese data support the use of rat seizure models in translational research aimed at evaluation and development of effective rTMS anticonvulsive protocols. We also offer a proof of principle that real-time analysis of EEG can be used to guide rTMS to suppress individual seizures.     

Electrical stimulation of left anterior thalamic nucleus with high-frequency and low-intensity currents reduces the rate of pilocarpine-induced epilepsy in rats

PurposeBilateral electrical stimulation of anterior nuclei of thalamus (ANT) has shown promising effects on epileptic seizures. However, bilateral implantation increases the risk of surgical complications and side effects. This study was undertaken to access the effectiveness of a stimulation paradigm involving high frequency and low intensity currents to stimulate the left ANT in rats.MethodsMale Sprague-Dawley rats were implanted with electroencephalogram (EEG) electrodes, and an additional concentric bipolar stimulation electrode into either the left or right ANT. The stimulus was a train of pulses (90 μs duration each) delivered with a frequency of 200 Hz and a current intensity of 50 μA. Thalamic stimuli were started 1 h before the first intraperitoneal pilocarpine injection (i.p., 300 mg/kg), and were applied for 5 h.ResultsEEG documented seizure activity and status epilepticus (SE) developed in 87.5% of rats treated with no ANT stimulation after a single dose of pilocarpine. Left ANT stimulation significantly increased the tolerance threshold for pilocarpine-induced EEG seizure activity; 20% of rats developed their EEG documented seizure activity after receiving the first dose, whereas 50%, 10% and 20% of rats did not develop seizure activity until they had received the 2nd, 3rd and 4th pilocarpine injection at 1-h intervals. Moreover, left thalamic stimulation reduced the occurrences of both EEG documented seizure activity and SE induced by single-dose pilocarpine to 25%. However, our result demonstrated that little effect on the occurrence rate of seizures and SE was found when rats received right ANT stimulation.ConclusionsThese results suggest that continuously 5-h left ANT stimulation with high frequency and low intensity currents, beginning from 1 h before the pilocarpine administration, may successfully reduce the occurrence rate of EEG documented seizure activity and SE development in rats.     

Multiple hippocampal transections for intractable hippocampal epilepsy: Seizure outcome

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

Retigabine calms seizure-induced behavior following status epilepticus

In adult rats, intraperitoneal injection of kainate (KA) results in sustained status epilepticus and persistent behavioral comorbidities such as hyperexcitability, anxiety, and altered response to environmental cues. Intrahippocampal KA also results in sustained status epilepticus and continuous high frequency oscillations in the electroencephalograph (EEG), although subsequent behavioral side effects are unknown. We hypothesized that retigabine, a recently discovered anticonvulsant and potent positive modulator of Kv7 channels, may attenuate seizure-induced behavioral abnormalities. Status epilepticus was induced by administration of KA either intraperitoneally (15 mg/kg) or by single intrahippocampal injection (1.0 μg/0.5 μL). After 24 h, half of systemically KA-treated animals that reached stage 6 seizures were injected once daily with retigabine (5 mg/kg) for 14 continuous days. All groups underwent three behavioral tests — capture and handling, open field, and elevated plus maze — 24 h following the last retigabine treatment and were sacrificed at 25–28 days. In the capture and handling test, systemic KA treatment resulted in frisky behavior and resistance to capture with wild attempts to escape during the 1st, 2nd, and 3rd weeks of the observation period. In contrast, these behaviors were attenuated in KA + retigabine-treated animals. In the open-field test, KA-treated animals spent more time in the center zone, but KA + retigabine-treated rats had greater overall activity compared with those having vehicle, KA, or retigabine-only treatment. In the elevated plus maze, KA + retigabine-treated animals traveled greater distances in open and closed arms (proximal and distal) compared with controls, also signifying anxiety reduction. Retigabine-only-treated rats traveled more in the open proximal arms compared with controls, indicating increased hyperlocomotion in normotensive rats. Although treatment with KA + retigabine resulted in anxiolytic-like effects in all three behavioral tasks compared with vehicle, this group did not significantly differ from systemically KA-treated rats in most measurements in open-field and elevated plus maze tasks, suggesting that retigabine may also cause hyperlocomotion unrelated to anxiety level. Despite that intrahippocampal KA-treated rats displayed comparable seizure behavior, epileptiform activity, and hippocampal injury, their behavior resembled the controls, suggesting that molecular and subsequent cellular changes are also partially responsible for anxiolytic-like effects and that these results are likely independent of the hippocampus.     

Duration of focal complex,secondarily generalized tonic–clonic,and primarily generalized tonic–clonic seizures — A video-EEG analysis

IntroductionIdentifying seizures with prolonged duration during video-electroencephalographic (EEG) monitoring is of importance to inform clinicians when to start emergency treatment of seizures to prevent status epilepticus. The aims of this study were to assess the clinical and EEG seizure duration (SD) in consecutive patients with epilepsy who underwent prolonged video-EEG monitoring and to identify a seizure type-dependent time point to start emergency treatment based on the likelihood that seizures will not stop spontaneously. Furthermore, we sought to determine predictors of SD and explored the relationship between antiepileptic drug (AED) serum levels and SD.Material and methodsWe retrospectively analyzed 1796 seizures in 200 patients undergoing video-EEG monitoring between January 2006 and March 2008.ResultsFocal simple seizures lasted significantly shorter (clinical SD: 28 s, EEG SD: 42 s) compared with focal complex seizures (clinical SD: 64 s, EEG SD: 62 s), and both seizure types lasted significantly shorter compared with secondarily generalized tonic–clonic seizures (GTCSs; clinical SD: 90 s, EEG SD: 96 s). There was no difference between the duration of the convulsive phase of primary GTCSs (defined as nonfocal) and that of secondarily GTCSs (each 65 s). Cumulative clinical SD (99%) was 7 min in focal complex seizures and 11 min in focal simple seizures. Mixed linear regression model demonstrated that history of status epilepticus (P = 0.034), temporal lobe seizure onset (P = 0.040), and MRI lesions (P = 0.013) were significantly associated with logarithmic EEG SD in focal epilepsies recorded with scalp electrodes. We found significant negative correlations between the AED serum level and the EEG SD in patients treated with monotherapy: carbamazepine (P < 0.001), levetiracetam (P = 0.001), oxcarbazepine (P = 0.001), and valproic acid (P = 0.038) but not with lamotrigine monotherapy and EEG SD.DiscussionBased on the results of this study, we propose 2 min of convulsive seizure activity (irrespective of focal or generalized onset) as a prolonged seizure, which could serve as a time point to consider treatment to prevent status epilepticus. In focal complex seizures, we suggest an upper limit of 7 min, and in focal simple seizures 11 min, as definition of prolonged seizures. History of status epilepticus, temporal seizure onset, and lesional MRI findings are factors associated with significantly longer SD. Negative correlations of carbamazepine, levetiracetam, oxcarbazepine, and valproic acid serum levels and SD suggest a prolonging effect on seizures during withdrawal of these AEDs during video-EEG monitoring sessions.This article is part of a Special Issue entitled “Status Epilepticus”.     

Frontal hemodynamic changes precede EEG onset of temporal lobe seizures

ObjectiveA preictal state exists minutes or hours prior to the clinical seizure. We investigated whether hemodynamic changes preceding temporal lobe seizures were detectable in frontal scalp recordings using near-infrared spectroscopy (NIRS). Patients undergoing video-EEG telemetry (VET) were studied.MethodsA NIRS sensor was placed over the frontal scalp ipsilateral to the patient’s first recorded seizure. Regional cerebral oxygenation (rSO2) was recorded synchronously with VET data and peripheral oxygen saturation (SaO2). Periictal changes in rSO2 were compared with baseline interictal rSO2.ResultsEleven seizures were recorded in six patients. A mean peak preictal increase in rSO2 of 7.1% from the interictal baseline (p < 0.001) occurred at a mean peak latency of 298.9 s before seizure onset. rSO2 then decreased around seizure onset. SaO2 nadir occurred at a mean latency of 62 s following rSO2 nadir. A postictal increase in rSO2 occurred with a mean duration of about 35 min. Periictal rSO2 changes occurred with both ipsi and contralateral temporal lobe seizures.ConclusionWe have shown that preictal changes in cerebral oxygenation occur with a mean peak latency of about 4.98 min before seizure onset.SignificanceNIRS has the potential for providing a noninvasively detected signal of an imminent seizure.     

Cardiac electrographic and morphological changes following status epilepticus: Effect of clonidine

PurposeStatus epilepticus has been increasingly associated with cardiac injury in both clinical and animal studies. Our group has previously shown that excitotoxic seizure induction results in the formation of ischaemic myocardial infarcts and loss of cardiac haemodynamic function. We hypothesised that attenuation of cardiac sympathetic/parasympathetic balance with a central presynaptic α₂ agonist, clonidine, can reduce the development of interictal ECG and ventricular morphological changes resulting from kainic acid (KA; 10 mg/kg) induced status epilepticus in a conscious rat model.MethodsUsing simultaneous ECG and electrocorticogram (ECoG) radiotelemetry, animals were randomised into saline controls, saline-pretreated KA and clonidine (100 μg/kg, b.i.d.)-pretreated KA groups. Baseline ECG, ECoG and behavioural score recordings were acquired in conscious animals for 2 h post-KA administration.ResultsBradycardia and low level seizure activity occurred immediately following KA administration. As seizure activity (ECoG spiking and high level seizure behavioural scoring) progressively increased, tachycardia developed. Both QTc prolongation and T wave amplitude were transiently but significantly increased. Clonidine treatment attenuated seizure activity, increased the latency to onset of seizure behaviour and reduced seizure-induced changes in heart rate, QTc interval, and T wave amplitude. Histological examination of the ventricular myocardium revealed hypercontraction band necrosis, inflammatory cell infiltration, and oedema at 48 h post-KA. In contrast, clonidine-treatment in seizure animals preserved tissue integrity and structure.ConclusionThese results demonstrate that KA-induced seizures are associated with altered ECG activity and cardiac structural pathology. We suggest that pharmacological modulation of sympathetic/parasympathetic activity in status epilepticus provides a promising therapeutic approach to reduce seizure-induced cardiomyopathy.     

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

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

Maximal electroshock-induced seizures are able to induce Homer1a mRNA expression but not pentylenetetrazole-induced seizures

ObjectiveHomer1a is a protein that regulates metabotropic glutamate receptors involved in neural plasticity processes. Recently, we demonstrated that Homer1a mRNA is enhanced after pilocarpine-induced status epilepticus. Here, we investigated whether a single acute seizure triggered by means of pentylenetetrazole (PTZ) injection or maximal electroshock (MES) stimulation (2 different seizure models) would alter Homer1a expression in the hippocampus.MethodsMale Wistar rats subjected to the PTZ or MES model were analyzed 2 h, 8 h, 24 h, and 7 days after seizure induction. Homer1a, mGluR1, and mGluR5 mRNA expression levels in hippocampal extracts were analyzed by quantitative PCR.ResultsQuantitative PCR revealed Homer1a overexpression at 2 h after MES-induced tonic–clonic seizures compared to control, but the overexpression did not remain elevated after 8 h. Pentylenetetrazole-induced seizures, in contrast, were not able to change Homer1a mRNA expression. No differences were observed at these time points after seizures for mGluR1 and mGluR5 mRNA expression in any of the models.SignificanceOur data indicate that the levels of Homer1a mRNA were transiently increased only after MES-induced tonic–clonic seizures (and not after PTZ-induced seizures). We suggest that Homer1a expression may be dependent on seizure intensity or on specific brain circuit activation. We suggest that Homer1a may contribute to counteract hyperexcitability processes.     

Comparison between febrile and afebrile seizures associated with mild rotavirus gastroenteritis

PurposeWe aimed on identifying the differences of febrile and afebrile seizures associated with mild rotavirus gastroenteritis (RVGE) in the pediatric population.MethodMedical charts of pediatric patients who had been admitted between July 1999 and June 2011 due to RVGE were retrospectively reviewed. Subjects were ultimately divided into three groups; ‘no seizure’ (NS: patients without seizure), ‘febrile seizure’ (FS: patients with fever during seizure), ‘afebrile seizure’ (AFS: patients without fever during seizure). Comparisons between groups were carried out on demographic and clinical characteristics, laboratory test results, electroencephalogram findings, brain magnetic resonance imaging findings, antiepileptic treatment, and prognosis.ResultsAmong the 755 subjects who had been admitted due to mild rotavirus enteritis, 696 (90.3%) did not have any seizures, 17 (2.2%) had febrile seizures, 42 (5.5%) had afebrile seizures. The duration of gastrointestinal symptoms before the onset of seizures were significantly shorter in the FS group compared to the AFS group (1.3 ± 0.8 vs. 2.8 ± 1.0 days; p < 0.0001). A single seizure attack was significantly higher in the AFS group (3.0 ± 1.6 vs. 1.7 ± 1.0 episodes; p = 0.0003), and the frequency of seizures that were of focal type with or without secondary generalization were significantly higher in the AFS group (33.3% vs. 6.0%; p = 0.0139). All patients among the FS and AFS group had not received further antiepileptic treatment after discharge, and none developed epilepsy during follow up period.ConclusionDespite some differences in seizure characteristics, both febrile and afebrile seizures associated with mild RVGE were mostly benign with a favorable prognosis.     

Visual and semiautomated evaluation of epileptogenicity in focal cortical dysplasias — An intracranial EEG study

IntroductionThe aim of the study was the evaluation of the added value of depth to subdural electrodes in delineating epileptogenicity of focal cortical dysplasias (FCDs) and to test the Epileptogenicity Index (EI) in this setting.Material and methodsFifteen patients with FCD underwent iEEG with subdural and depth electrodes. Visual/EI analysis was performed in up to three habitual seizures per patient.ResultsVisual analysis: Grid onset seizures (n = 10) started in electrodes overlying the lesion in 7 and remote from it in 3 cases. Depth onset seizures (n = 7) affected only intralesional contacts in 4, intra- and extralesional in 2, and exclusively extralesional in 1 patient. Seizures started in depth and grid contacts simultaneously in 2 cases.EI analysis: The EI completely confirmed visual localization of seizure onset in 8 cases and depicted ictal onset-time accurately in 13. Beta/gamma ictal patterns were most reliably captured.Impact on surgical decision: Resection outline differed from MRI lesion in 7 patients based on grid and in three based on depth electrode information.DiscussionIn FCD, seizures can be generated within gyral/deep tissue appearing normal on imaging.ConclusionInvestigating FCD with subdural and depth electrodes is efficient to outline the seizure onset zone. The EI is a helpful additional tool to quantify epileptogenicity. Specific ictal patterns are prerequisite for reliable results.     

Distribution of regional gray matter abnormalities in a pediatric population with temporal lobe epilepsy and correlation with neuropsychological performance

ObjectiveThe goals of the work described here were to determine if hippocampal and extrahippocampal atrophy in children with temporal lobe epilepsy (TLE) follows a pattern similar to that in adult patients, and to assess the clinical and neuropsychological relevance of regional brain atrophy in pediatric TLE.MethodsChildren with symptomatic TLE (n = 14: 9 with mesial TLE due to hippocampal atrophy and 5 with TLE due to neocortical lesions), healthy children (n = 14), and 9 adults with mesial temporal lobe epilepsy (MTLE) were compared using voxel-based morphometry (VBM) of brain magnetic resonance imaging (MRI). The children underwent a comprehensive neuropsychological battery.ResultsChildren with MTLE with unilateral hippocampal atrophy (n = 9) exhibited a significant reduction in gray matter in the hippocampus ipsilateral to the seizure origin and significant atrophy in the ipsilateral cingulate gyrus and contralateral middle frontal lobe. Children with TLE (n = 14) exhibited a significant reduction in the gray matter of the ipsilateral hippocampus and parahippocampal gyrus. There was a correlation between gray matter volume in children with TLE and scores on several neuropsychological tests. Atrophy in pediatric patients with MTLE was less extensive than that in adults, and involved the hippocampi and the frontal cortex.ConclusionsSimilar to adult MTLE, pediatric MTLE is associated with hippocampal and extrahippocampal cell loss. However, children display less intense quantifiable gray matter atrophy, which affects predominantly frontal lobe areas. There was a significant association between volume of gray matter in medial temporal and frontal regions and scores on neuropsychological tests. In childhood, TLE and the concomitant cognitive/behavior disturbances are the result of a damaged neural network.     

Bimodal ultradian seizure periodicity in human mesial temporal lobe epilepsy

BackgroundMesial temporal lobe epilepsy (mTLE) has been suggested to follow a circadian rhythm. Previous research found an afternoon peak in mTLE seizure occurrence. We evaluated the pattern of seizure occurrence in patients with well-localized mTLE and hypothesized that peak seizure frequency would occur in the afternoon, and that this pattern would not be altered by age, gender, or seizure focus.MethodsWe retrospectively identified consecutive mTLE patients with a seizure-free outcome following anterior temporal lobectomy from 1993 to 2004 with video-EEG captured seizures. We recorded and plotted the 24-h clock time for each seizure and performed cosinor analysis. SAS Proc GLIMMIX was used to fit the linearized transform of the cosinor model. Negative binomial regression fitted by the generalized estimating equations (GEE) method was also performed to estimate and compare the mean seizure rates over a 24-h day.ResultsSixty mTLE patients monitored between 2 and 16 days were analyzed. Mean (standard deviation), median number of seizures per subject were 10.47(7.86), 9.00. Cosinor plots indicated that the function had two modes: 7–8 a.m. and 4–5 p.m. GEE analysis was consistent with peak seizure frequency occurrence at 6–8 a.m. (p < 0.0001) and 3–5 p.m. (p < 0.01).ConclusionsWe found a bimodal pattern of seizure occurrence in human mTLE, with peak seizure frequencies occurring between 6–8 a.m. and 3–5 p.m. confirming an afternoon peak, as well as a previously unsuspected morning peak in seizure occurrence that provides rationale for future investigations of antiepileptic drug chronopharmacology and informs patient counseling regarding patterns of seizure occurrence.     

Electrode location and clinical outcome in hippocampal electrical stimulation for mesial temporal lobe epilepsy

PurposeTo study the clinical outcome in hippocampal deep brain stimulation (DBS) for the treatment of patients with refractory mesial temporal lobe epilepsy (MTLE) according to the electrode location.MethodsEight MTLE patients implanted in the hippocampus and stimulated with high-frequency DBS were included in this study. Five underwent invasive recordings with depth electrodes to localize ictal onset zone prior to chronic DBS. Position of the active contacts of the electrode was calculated on postoperative imaging. The distances to the ictal onset zone were measured as well as atlas-based hippocampus structures impacted by stimulation were identified. Both were correlated with seizure frequency reduction.ResultsThe distances between active electrode location and estimated ictal onset zone were 11 ± 4.3 or 9.1 ± 2.3 mm for patients with a >50% or <50% reduction in seizure frequency. In patients (N = 6) showing a >50% seizure frequency reduction, 100% had the active contacts located <3 mm from the subiculum (p < 0.05). The 2 non-responders patients were stimulated on contacts located >3 mm to the subiculum.ConclusionDecrease of epileptogenic activity induced by hippocampal DBS in refractory MTLE: (1) seems not directly associated with the vicinity of active electrode to the ictal focus determined by invasive recordings; (2) might be obtained through the neuromodulation of the subiculum.     

Risk factors for valproic acid resistance in childhood absence epilepsy

AimsValproic acid (VPA) is reported to be effective for the control of absence seizures in 75% of children. The aim of this study was to determine the clinical and socio-demographic factors associated with VPA response in newly diagnosed childhood absence epilepsy (CAE) and to determine if these factors also influence the chances of achieving long-term seizure freedom.MethodsMedical charts of 180 children with CAE were retrospectively reviewed. Clinical, electroencephalographic and imaging findings were recorded to correlate with complete VPA response and long-term epilepsy outcome. Factors associated with non-responsiveness were identified individually and in a multivariable logistic regression analysis.ResultsTreatment was successful in 112 (58.3%) children. More children that were non-responsive to VPA experienced generalized tonic clonic seizures (GTCS) (33.8% vs. 13.4% for responders; p = 0.001) and 52.9% had a pre-treatment seizure frequency greater than 10/day (vs. 27.0% for responders; p < 0.001). Finally, responders were older at time of diagnosis versus non-responders (p = 0.001). Absence of long-term seizure freedom was linked to the presence of GTCS, the absence of initial response and the need for multiple AEDs to control seizures.InterpretationOur results suggest that clinical phenotypes are associated with reduced response rates to VPA. This should be taken into account when counselling families of children with newly diagnosed absence epilepsy.     

Is elevated pre-ictal heart rate associated with secondary generalization in partial epilepsy?

BackgroundPeople with epilepsy are at risk for sudden unexpected death. Cardiac arrhythmia is one possible mechanism. We have studied seizure-related changes in cardiac rhythm.MethodsVideo-EEG and ECG from 38 patients with epileptic seizures during long-term monitoring for investigation of partial epilepsy with ictal impairment of consciousness were obtained. Seizures were classified as either complex partial or secondarily generalized. Inter-ictal, pre-ictal, ictal and post-ictal heart rate was calculated for the first recorded seizure.ResultsHeart rate during the pre-ictal period was higher (p = 0.016) in patients with secondarily generalized seizures (n = 11) compared to patients with complex partial seizures (n = 27). Heart rate was also elevated during and after generalized seizures (p < 0.015). Inter-ictal heart rate was not different in patients with secondary generalization compared to patients with partial seizures.ConclusionWe report elevated heart rate prior to partial seizure onset in those attacks which become secondarily generalized compared to seizures which remain localized. The finding may be relevant for the understanding of sudden death in epilepsy.     

Predictors of seizure occurrence in children undergoing pre-surgical monitoring

PurposeLong-Term-Monitoring (LTM) is a valuable tool for seizure localization/lateralization among children with refractory-epilepsy undergoing pre-surgical-monitoring. The aim of this study was to examine the factors predicting occurrence of single/multiple seizures in children undergoing pre-surgical monitoring in the LTM unit.MethodsChart review was done on 95 consecutive admissions on 92 children (40 females) admitted to the LTM-unit for pre-surgical workup. Relationship between occurrence of multiple (≥3) seizures and factors such as home seizure-frequency, demographics, MRI-lesions/seizure-type and localization/AED usage/neurological-exam/epilepsy-duration was evaluated by logistic-regression and survival-analysis. Home seizure-frequency was further categorized into low (up-to 1/month), medium (up-to 1/week) and high (>1/week) and relationship of these categories to the occurrence of multiple seizures was evaluated. Mean length of stay was 5.24 days in all 3 groups.ResultsHome seizure frequency was the only factor predicting the occurrence of single/multiple seizures in children undergoing presurgical workup. Other factors (age/sex/MRI-lesions/seizure-type and localization/AED-usage/neurological-exam/epilepsy-duration) did not affect occurrence of single/multiple seizures or time-to-occurrence of first/second seizure.Analysis of the home-seizure frequency categories revealed that 98% admissions in high-frequency, 94% in the medium, and 77% in low-frequency group had at-least 1 seizure recorded during the monitoring. Odds of first-seizure increased in high vs. low-frequency group (p = 0.01). Eighty-nine percent admissions in high-frequency, 78% in medium frequency, versus 50% in low-frequency group had ≥3 seizures. The odds of having ≥3 seizures increased in high-frequency (p = 0.0005) and in medium-frequency (p = 0.007), compared to low-frequency group. Mean time-to-first-seizure was 2.7 days in low-frequency, 2.1 days in medium, and 2 days in high-frequency group. Time-to-first-seizure in high and medium-frequency was less than in low-frequency group (p < 0.0014 and p = 0.038).ConclusionMajority of the admissions (92%) admitted to the LTM-unit for pre-surgical workup had at-least one seizure during a mean length of stay of 5.24 days. Home seizure-frequency was the only predictor influencing occurrence of single/multiple seizures in the LTM unit. Patients with low seizure-frequency are at risk for completing the monitoring with less than the optimum number (<3) of seizures captured.     

Differential impact of contraceptive methods on seizures varies by antiepileptic drug category: Findings of the Epilepsy Birth Control Registry

PurposeThe aim of this study was to determine whether categories of contraception differ in their impact on seizures in women with epilepsy and whether the impact varies by antiepileptic drug category.MethodsRetrospective survey data came from 2712 contraceptive experiences reported by 1144 women with epilepsy. We compared risk ratios for reports of increase and decrease in seizure frequency on hormonal versus nonhormonal contraception, stratified by antiepileptic drug categories.ResultsMore women with epilepsy reported a change in seizures on hormonal (28.2%) than on nonhormonal contraception (9.7%) (p < 0.0001). The risk ratio for seizure increase on hormonal (18.7%) versus nonhormonal contraception (4.2%) was 4.47 (p < 0.0001). The risk ratio for seizure decrease on hormonal (9.5%) versus nonhormonal contraception (5.5%) was 1.71, p < 0.0001. On hormonal contraception, the risk ratio for seizure increase was greater than for decrease (1.98, p < 0.0001). In comparison to combined pills, both hormonal patch and progestin-only pills had greater risk ratios for seizure increase. Depomedroxyprogesterone was the only hormonal method with a greater risk ratio for seizure decrease than combined pills. Seizure increase was greater for hormonal than nonhormonal contraception for each antiepileptic drug category (p < 0.001). On hormonal contraception, relative to the non-enzyme-inducing antiepileptic drug category which had the lowest rate, each of the other categories had significantly greater risks for seizure increase, especially the enzyme-inhibiting (valproate) category (risk ratio = 2.53, p = 0.0002).ConclusionThe findings provide community-based, epidemiological survey evidence that contraceptive methods may differ in their impact on seizures and that this impact may vary by antiepileptic drug category.     

Real-time automated detection of clonic seizures in newborns

ObjectiveThe aim of this study is to apply a real-time algorithm for clonic neonatal seizures detection, based on a low complexity image processing approach extracting the differential average luminance from videotaped body movements.Methods23 video-EEGs from 12 patients containing 78 electrographically confirmed neonatal seizures of clonic type were reviewed and all movements were divided into noise, random movements, clonic seizures or other seizure types. Six video-EEGs from 5 newborns without seizures were also reviewed. Videos were then separately analyzed using either single, double or triple windows (these latter with 50% overlap) each of a 10 s duration.ResultsWith a decision threshold set at 0.5, we obtained a sensitivity of 71% (corresponding specificity: 69%) with double-window processing for clonic seizures diagnosis. The discriminatory power, indicated by the Area Under the Curve (AUC), is higher with two interlaced windows (AUC = 0.796) than with single (AUC = 0.788) or triple-window (AUC = 0.728). Among subjects without neonatal seizures, our algorithm showed a specificity of 91% with double-window processing.ConclusionsOur algorithm reliably detects neonatal clonic seizures and differentiates them from either noise, random movements and other seizure types.SignificanceIt could represent a low-cost, low complexity, real-time automated screening tool for clonic neonatal seizures.