Acute and spontaneous seizure onset zones in the intraperitoneal kainic acid model

ObjectiveHippocampal monitoring is often used in the intraperitoneal kainic acid (KA) seizure model for detection and quantification of early ictal activity. Here, we investigated extra-hippocampal seizure onset zones (SOZs) in this model.MethodsEight male Sprague Dawley rats implanted with depth electrodes were continuously recorded during intraperitoneal KA injections until status epilepticus (SE) was induced. Another group of four rats was monitored chronically up to two weeks after emergence of spontaneous recurrent seizures. All rats had hippocampal electrodes. Other sampled brain regions included, among others, the claustrum, piriform cortex, and orbital cortex. Seizures recorded with video-EEG were visually analyzed.ResultsIn the 58 seizures recorded during KA injections, the SOZ was extrahippocampal in 7 (12%), diffuse in 29 (50%), and hippocampal in 22 (38%). Of the 14 spontaneous seizures recorded, none were solely extrahippocampal, 10 (71%) were diffuse, and 4 (29%) were of hippocampal onset. All extra-hippocampal seizures propagated to the hippocampus within 4 to 50 s (mean = 14, n = 7). No distinctive semiological manifestations correlated with the SOZs.SignificanceWe conclude that seizures can have multifocal SOZs in the KA model. This finding is important to consider when using this model, among other purposes, to screen for new therapies, study pharmacoresistance, or investigate comorbidities of epilepsy.     

The effects of vagus nerve stimulation on tryptophan metabolites in children with intractable epilepsy

BackgroundThe mechanism of action of vagus nerve stimulation (VNS) in intractable epilepsy is not entirely clarified. It is believed that VNS causes alterations in cytokines, which can lead to rebalancing the release of neurotoxic and neuroprotective tryptophan metabolites. We aimed to evaluate VNS effects on tryptophan metabolites and on epileptic seizures and investigated whether the antiepileptic effectiveness correlated with changes in tryptophan metabolism.MethodsForty-one children with intractable epilepsy were included in a randomized, active-controlled, double-blind study. After a baseline period of 12 weeks, all children underwent implantation of a vagus nerve stimulator and entered a blinded active-controlled phase of 20 weeks. Half of the children received high-output (therapeutic) stimulation (n = 21), while the other half received low-output (active control) stimulation (n = 20). Subsequently, all children received high-output stimulation for another 19 weeks (add-on phase). Tryptophan metabolites were assessed in plasma and cerebrospinal fluid (CSF) by use of liquid chromatography–tandem mass spectrometry (LC–MS/MS) and compared between high- and low-output groups and between the end of both study phases and baseline. Seizure frequency was recorded using seizure diaries. Mood was assessed using Profile of Mood States (POMS) questionnaires.ResultsRegarding tryptophan metabolites, anthranilic acid (AA) levels were significantly higher at the end of the add-on phase compared with baseline (p = 0.002) and correlated significantly with improvement of mood (τ = − 0.39, p = 0.037) and seizure frequency reduction (τ = − 0.33, p < 0.01). No significant changes were found between high- and low-output groups regarding seizure frequency.ConclusionVagus nerve stimulation induces a consistent increase in AA, a neuroprotective and anticonvulsant tryptophan metabolite. Moreover, increased AA levels are associated with improvement in mood and reduction of seizure frequency.     

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.     

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.     

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”.     

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.     

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.     

Children with new onset seizures: A prospective study of parent variables,child behavior problems,and seizure occurrence

ObjectiveParent variables (stigma, mood, unmet needs for information and support, and worry) are associated with behavioral difficulties in children with seizures; however, it is not known how this relationship is influenced by additional seizures. This study followed children (ages 4–14 years) and their parents over a 24-month period (with data collected at baseline and 6, 12, and 24 months) and investigated the effect of an additional seizure on the relationship between parenting variables and child behavior difficulties.MethodsThe sample was parents of 196 children (104 girls and 92 boys) with a first seizure within the past 6 weeks. Child mean age at baseline was 8 years, 3 months (SD 3 years). Data were analyzed using t-tests, chi-square tests, and repeated measures analyses of covariance.ResultsRelationships between parent variables, additional seizures, and child behavior problems were consistent across time. Several associations between parent variables and child behavior problems were stronger in the additional seizure group than in the no additional seizure group.ConclusionsFindings suggest that interventions that assist families to respond constructively to the reactions of others regarding their child's seizure condition and to address their needs for information and support could help families of children with continuing seizures to have an improved quality of life.     

The value of video-EEG monitoring to diagnose juvenile myoclonic epilepsy

ObjectiveA diagnostic accuracy of conventional electroencephalography (EEG) is approximately 50% at best. We aimed to determine the accuracy of video-EEG monitoring (VEM) for a correct diagnosis and the feasibility of its clinical application. The data from all 55 patients (M:F = 31:24) with juvenile myoclonic epilepsy (JME) who underwent VEM were reviewed according to the clinical history, brain imaging and video-EEG findings.ResultsAge at seizure onset ranged from 10 to 25 (15.5 ± 2.7 years). The age at VEM ranged from 15 to 46 (21.8 ± 5.8 years) and 57% (29/51) showed seizures. Of those, 20 patients (69%) showed myoclonic jerks alone, whereas 3 (10%) showed generalized seizures alone. Both of these conditions were observed in 6 patients (21%). Interictal abnormalities alone without clinical seizures were detected in 16 patients (31%). Atypical semiologies such as asymmetric myoclonus or versive seizures were observed in 18 patients (35%) during video monitoring. Interestingly three patients complained of visual aura on history. The duration of VEM ranged from 1 to 6 days (1.8 ± 1.1). Overall, 88% of patients showed an EEG abnormality with/without seizure, concordant with JME. Among 10 patients with a normal conventional EEG before VEM, 9 showed interictal or ictal EEG abnormalities during approximately 1-day of VEM.ConclusionsVEM for 1 or 2 days is appropriate for making a correct diagnosis of JME, especially in patients having an atypical semiology and a normal result on the conventional EEG.     

Seizure clusters and adverse events during pre-surgical video-EEG monitoring with a slow anti-epileptic drug (AED) taper

ObjectiveTo evaluate the efficiency and safety of pre-surgical video-EEG monitoring with a slow anti-epileptic drug (AED) taper and a rescue benzodiazepine protocol.MethodsFifty-four consecutive patients with refractory focal epilepsy who underwent pre-surgical video-electroencephalography (EEG) monitoring during the year 2010 were included in the study. Time to first seizure, duration of monitoring, incidence of 4-h and 24-h seizure clustering, secondarily generalised tonic–clonic seizures (sGTCS), status epilepticus, falls and cardiac asystole were evaluated.ResultsA total of 190 seizures were recorded. Six (11%) patients had 4-h clusters and 21 (39%) patients had 24-h clusters. While 15 sGTCS were recorded in 14 patients (26%), status epilepticus did not occur and no seizure was complicated with cardiac asystole. Epileptic falls with no significant injuries occurred in three patients. The mean time to first seizure was 3.3 days and the time to conclude video-EEG monitoring averaged 6 days.ConclusionSeizure clustering was common during pre-surgical video-EEG monitoring, although serious adverse events were rare with a slow AED tapering and a rescue benzodiazepine protocol.SignificanceSlow AED taper pre-surgical video-EEG monitoring is fairly safe when performed in a highly specialised and supervised hospital setting.     

A prospective long-term study of external trigeminal nerve stimulation for drug-resistant epilepsy

BackgroundExternal trigeminal nerve stimulation (eTNS) is an emerging noninvasive therapy for drug-resistant epilepsy (DRE). We report the long-term safety and efficacy of eTNS after completion of a phase II randomized controlled clinical trial for drug-resistant epilepsy.MethodsThis was a prospective open-label long-term study. Subjects who completed the phase II randomized controlled trial of eTNS for DRE were offered long-term follow-up for 1 year. Subjects who were originally randomized to control settings were crossed over to effective device parameters (30 s on, 30 s off, pulse duration of 250 s, frequency of 120 Hz). Efficacy was assessed using last observation carried forward or parametric imputation methods for missing data points. Outcomes included change in median seizure frequency, RRATIO, and 50% responder rate.ResultsThirty-five of 50 subjects from the acute double-blind randomized controlled study continued in the long-term study. External trigeminal nerve stimulation was well tolerated. No serious device-related adverse events occurred through 12 months of long-term treatment. At six and twelve months, the median seizure frequency for the original treatment group decreased by -2.39 seizures per month at 6 months (-27.4%) and -3.03 seizures per month at 12 months (-34.8%), respectively, from the initial baseline (p < 0.05, signed-rank test). The 50% responder rates at three, six, and twelve months were 36.8% for the treatment group and 30.6% for all subjects.ConclusionThe results provide long-term evidence that external trigeminal nerve stimulation is a safe and promising long-term treatment for drug-resistant epilepsy.     

Gender and age influence in daytime and nighttime seizure occurrence in epilepsy associated with mesial temporal sclerosis

ObjectivesThe aim of this study was to analyze the daytime and nighttime seizure distribution during video-EEG monitoring in patients with epilepsy associated with unilateral mesial temporal sclerosis (MTS) and the role of gender, age, and lesion side on 24-hour seizure distribution.MethodsWe studied 167 consecutive adult (age ≥ 16 years) patients with epilepsy associated with unilateral mesial temporal sclerosis that had three or more recorded seizures during continuous video-EEG monitoring with a minimum recording time period of 24 h. Seizure onset time was classified according to occurrence in six 4-hour periods.ResultsSeven hundred thirty-five seizures were evaluated. We observed two higher seizure occurrence periods: 08:01–12:00 (p = 0.001) and 16:01–20:00 (p = 0.03). Significantly fewer seizures were observed between 0:01 and 4:00 (p = 0.01). Nonuniform seizure distribution was noted in women (p < 0.0001), in young patients (less than 45 years of age) (p < 0.0001), and in both patients with left (p = 0.03) and patients with right mesial temporal sclerosis (p = 0.008). Men presented uniform seizure occurrence distribution (p = 0.15). Women had fewer seizures than expected and fewer seizures than men between 0:01–04:00 (p < 0.0001 and p = 0.0015, respectively) and 04:01–08:00 (p = 0.01 and p = 0.03, respectively). Young patients (age < 45 years) had two seizure occurrence peaks, 08:01–12:00 (p = 0.016) and 16:01–20:00 (p = 0.004). Middle-aged/old patients (≥ 45 years) had only one seizure occurrence peak, 08:01–12:00 (p = 0.012). Young patients had more seizures than middle-aged/old patients between 16:01–20:00 (p = 0.04). No differences were noted between left and right MTS.SignificanceWe observed two seizure occurrence peaks: morning and late afternoon/evening. We encountered variations in daytime and nighttime seizure distribution according to gender and age, but not according to side of MTS. Future studies are needed to confirm these findings and to unravel the neurobiological substrate underlying daytime and nighttime variations of seizure occurrence in different age groups and between genders.     

A reduction of sleep spindles heralds seizures in focal epilepsy

ObjectivesSleep has profound effects on epilepsy. It may alter the occurrence of interictal discharges (IEDs) and seizures. Vice versa, an active epilepsy changes sleep. Sleep spindles are typically associated with an increase of IEDs. We examined whether seizures change the number and power of spindles preceding nightly seizures.MethodsWe retrospectively examined the nightly EEG recordings of presurgical epilepsy patients from our EEG-video-monitoring unit. We evaluated the 200 s before the EEG seizure onset for spindle density (spindles per minute) and spindle power and compared that to the interictal baseline sleep.ResultsThe spindle density and the spindle power decreased significantly before the first seizure. The reduction before secondarily generalized seizures (8.7 ± 2.5; p = 0.001) was more pronounced than before focal seizures (10.5 ± 2.5; p = 0.003) compared to baseline (12.2 ± 2.7). This finding was more pronounced in extratemporal lobe epilepsies than in temporal lobe epilepsies. The reduction of spindle power was also significant and was more pronounced in XTLE. These results were consistent for all other seizures during sleep, the mean spindle density decreased significantly in all focal (10.2 ± 1.9; p = 0.001) and generalized preictal period (8.8 ± 2.4; p = 0.001) compared to the mean interictal period (12.1 ± 2.1). These were also more significant in XTLE than TLE group.ConclusionsOur data demonstrate that the occurrence of seizures and propensity of seizure generalisation in focal epilepsy is modulated by specific characteristics of light sleep such as sleep spindles.SignificanceThis study supports the notion that changes in the epileptic network precede the seizure onset and have an influence on seizure generation and termination.     

Prospective audit with adjunctive perampanel: Preliminary observations in focal epilepsy

PurposePerampanel (PER) was first licensed in the United Kingdom in 2012 for the adjunctive treatment of focal seizures with or without secondary generalization in adults and children over 12 years of age. It has recently also been approved for use as add-on therapy for patients with primary generalized tonic–clonic seizures. This prospective audit reports preliminary outcomes with adjunctive PER in patients with focal-onset seizures in everyday clinical practice using a standard design.MethodsTo date, 54 patients (38 males, 16 females; 21–65 years, median: 48 years) have completed the study. The median monthly seizure frequency was 4 (range: 1–60). At baseline, patients were taking a median of 2 other antiepileptic drugs (range: 1–4 drugs), with their seizures having previously failed to improve on a median of 3 schedules (range: 1–15 schedules). After 12 weeks of stable dosing, PER was added, aiming at a target range of 6–12 mg/daily. Review took place every 6–8 weeks until one of 4 endpoints was reached: seizure freedom for ≥ 6 months on a given PER dose, ≥ 50% (responder) or < 50% (marginal effect) seizure reduction over 6 months, compared with the prospective baseline, on the highest tolerated PER dose, or withdrawal of PER due to a lack of efficacy or side effects.ResultsThree (5.6%) patients have remained seizure-free, with 8 (14.8%) demonstrating a ≥ 50% response and a further 17 (31.5%) reporting a marginal effect. Of the 26 (48.1%) dropping out of PER treatment, 21 (38.9%) did so because of side effects. The commonest problems were nausea, vomiting, ataxia, dizziness, and sedation. Overall, 6 (11%) patients developed neuropsychiatric problems, with 3 reporting irritability and/or aggression. Two patients had substantial weight gain, and another patient suffered recurrent falls. Treatment with enzyme-inducing AEDs had no effect on PER dosing in patients responding to PER or withdrawing due to side effects.SignificanceThese data support the value of adjunctive PER in some patients with pharmacoresistant epilepsy in everyday clinical practice.     

Prevalence and correlates of major depressive disorder (MDD) among adolescent patients with epilepsy attending a Nigerian neuropsychiatric hospital

BackgroundA high prevalence of mood disorders exists in patients with epilepsy. In most cases, this is not detected and, consequently, not treated. This study aimed to determine the prevalence and correlates of major depressive disorder (MDD) among adolescents with epilepsy attending a child and adolescent clinic in Nigeria.MethodsWe recruited 156 participants consecutively for the study. Adherence was assessed using the 8-item Morisky Medication Adherence Questionnaire, while the K-SADS was used to assess the presence of major depressive disorder. Seizure control was evaluated by the frequency of seizures within a year.ResultsMajor depressive disorder (DSM-IV criteria) was diagnosed in 28.2% of the participants. The age of participants (p = 0.013), seizure control (p = 0.03), medication adherence (p = 0.045), frequency of seizures in the preceding 4 weeks (p < 0.001), and duration of illness (p < 0.001) were all significantly associated with the presence of MDD. Participants with seizures occurring more than once weekly in the preceding 4 weeks were 16 times more likely to have a MDD compared with those with no seizures in the preceding 4 weeks (p < 0.001, 95% C.I. [4.13, 65.43]), while participants with a duration of illness more than 10 years were more than four times likely to have MDD compared with those with an illness duration of 5–10 years (p < 0.01, 95% C.I. [0.07, 0.70]).ConclusionThe prevalence of MDD among patients with epilepsy was high. Poor seizure control, poor medication adherence, and long duration of illness were associated with the presence of MDD among such patients. Intervention should focus on ensuring good seizure control and optimal adherence in order to mitigate the impact of MDD in patients with epilepsy.     

Utility of long-term video-EEG monitoring for children with staring

ObjectiveStaring spells are a common reason for referral to overnight epilepsy monitoring unit (EMU) evaluation. However, inpatient EMU admissions are expensive and time consuming. This study determined what percentage of those referred for staring had a confirmed epileptic seizure on long-term video-EEG monitoring (LTM) and developed a scoring system to help prioritize which patients should undergo this procedure.MethodsWe performed a four-year retrospective chart review of all children at a tertiary pediatric hospital who received LTM (long-term monitoring) for the purposes of characterizing staring. The two goals were to: a) assess how often an LTM admission captured a staring spell that was diagnosed as a seizure and b) determine if any baseline factors predicted this particular positive result. We coded several characteristics of the most recent prior routine EEG if available. We also coded parental reports of the duration, frequency, and breakability of the events as well as post-ictal mental status and the presence/absence of automatisms. Finally, we coded previous neurological and psychiatric diagnoses and medications, as well as family history of epilepsy.ResultsOf the 276 admissions, only 29 (11%) captured a staring spell and diagnosed it as seizure. Several baseline variables predicted the likelihood of this positive result. Based on this information, we created a scoring system as follows: − 3 points if the previous EEG was normal, − 1 point if the child took a medication for a psychiatric condition, + 1 point if the child took an anti-epileptic drug for epilepsy, and + 1 point if the spells lasted less than 1 min. If the total score was zero or less, staring spells diagnosed as seizures rarely occurred (less than 5% of the studies).SignificanceOur scoring system shows how consideration of prior EEG findings, medication history, and staring spell duration can help prioritize patients for LTM admission to evaluate if staring spells are epileptic seizures.     

The neuropsychological outcome of pediatric patients with refractory epilepsy treated with VNS — A 24-month follow-up in Taiwan

ObjectivesMultiple studies have reported the benefits of vagus nerve stimulation (VNS) on neuropsychological outcomes. The aim of this study was to investigate how VNS affects cognition and psychosocial adjustment in children with refractory epilepsy (RE), and to determine the efficacy of VNS in a Taiwanese population.MethodsWe conducted a one-group pretest–posttest study on pediatric patients with RE. The study comprised 19 males and 18 females, all aged < 18 years. We recorded seizure frequency at 3, 12, and 24 months after VNS device implantation. Intelligence quotients (IQ) were assessed using the Wechsler Intelligence Scale for Children — IV. The Parental Stress Index (PSI) scores were evaluated by a pediatric psychologist.ResultsVagus nerve stimulation device implantation significantly reduced seizure frequency at 3, 12 and 24 months, especially in young children (< 12 years). No significant improvement in IQ test performance was observed, though there were significant improvements in the PSI, especially in young children.ConclusionsVagus nerve stimulation device implantation does not significantly improve cognition function, but it does significantly reduce seizure frequency and stress in parent–child relationships, especially in young children (< 12 years). These findings suggest that VNS should be considered as an alternative therapy for patients proven to have seizures that are medically refractory, especially those younger than 12 years of age.     

Sleep quality and daytime sleepiness in patients treated with adjunctive perampanel for focal seizures

PurposeThe purpose of this study was to evaluate subjective sleep quality and daytime sleepiness in patients receiving adjunctive perampanel for focal seizures.MethodsWe conducted a multicenter, prospective, interventional, open-label study in patients aged > 16 with focal seizures who received adjunctive perampanel (flexible dosing: 2–12 mg). Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI) and daytime sleepiness with the Epworth Sleepiness Scale (ESS) at baseline and 3 and 6 months after initiating perampanel. Patients with modifications in their baseline AEDs or sleep medications were excluded.ResultsIn 72 patients with drug-resistant focal seizures, mean baseline PSQI score (± standard deviation) was 7.26 (± 4.6), and ESS was 6.19 (± 4.2). At 3 months (median perampanel dose: 4 mg), there was no significant mean change from baseline in ESS score (n = 61) and a significant improvement in PSQI (− 1.51 points; n = 44; p = 0.007), driven mainly by improved sleep efficiency (p = 0.012). In the 31 patients with 6-month data, ESS (but not PSQI) improved significantly at 6 months vs baseline (p = 0.029). The only factor significantly correlated with sleep parameters was number of baseline AEDs (higher number correlated with worse daytime sleepiness). Seizure frequency was reduced significantly from baseline at 3 and 6 months. In bivariate analysis, neither PSQI nor ESS was associated with seizure frequency, suggesting that the changes in daytime sleepiness and sleep quality may be independent of the direct effect on seizures.ConclusionAdjunctive perampanel did not worsen sleep quality or daytime sleepiness at 3 months and reduced daytime sleepiness in patients continuing perampanel for 6 months. Perampanel may be a suitable AED in patients with sleep disorders, in addition to refractory focal seizures.     

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.     

Severity and burden of partial-onset seizures in a phase III trial of eslicarbazepine acetate

ObjectiveThe objective of this study was to compare posttreatment seizure severity in a phase III clinical trial of eslicarbazepine acetate (ESL) as adjunctive treatment of refractory partial-onset seizures.MethodsThe Seizure Severity Questionnaire (SSQ) was administered at baseline and posttreatment. The SSQ total score (TS) and component scores (frequency and helpfulness of warning signs before seizures [BS]; severity and bothersomeness of ictal movement and altered consciousness during seizures [DS]; cognitive, emotional, and physical aspects of postictal recovery after seizures [AS]; and overall severity and bothersomeness [SB]) were calculated for the per-protocol population. Analysis of covariance, adjusted for baseline scores, estimated differences in posttreatment least square means between treatment arms.ResultsOut of 547 per-protocol patients, 441 had valid SSQ TS both at baseline and posttreatment. Mean posttreatment TS for ESL 1200 mg/day was significantly lower than that for placebo (2.68 vs 3.20, p < 0.001), exceeding the minimal clinically important difference (MCID: 0.48). Mean DS, AS, and SB were also significantly lower with ESL 1200 mg/day; differences in AS and SB exceeded the MCIDs. The TS, DS, AS, and SB were lower for ESL 800 mg/day than for placebo; only SB was significant (p = 0.013). For both ESL arms combined versus placebo, mean scores differed significantly for TS (p = 0.006), DS (p = 0.031), and SB (p = 0.001).ConclusionsTherapeutic ESL doses led to clinically meaningful, dose-dependent reductions in seizure severity, as measured by SSQ scores.Classification of evidenceThis study presents Class I evidence that adjunctive ESL (800 and 1200 mg/day) led to clinically meaningful, dose-dependent seizure severity reductions, measured by the SSQ.