Antiepileptic Drug Changes Research Articles

Utility of Routine EEG in Emergency Department and Inpatient Service.

The most important indication for EEGs is the investigation of epileptic and nonepileptic seizures. However, it is unclear whether EEG in the emergency depatment (ED) can be useful in managing other conditions. Our objective was to investigate the usefulness of EEGs in the ED. We performed an observational, descriptive, retrospective study based on clinical records between 2018 and 2019. We evaluated patients admitted to our ED or hospital wards who underwent an EEG. We defined the EEG results as useful when they prompted changes in antiepileptic drug (AED) treatment or clinical management. We gathered information from 236 patients with a mean age of 59.23 years (SD ±22.6), of whom 47.9% were women. In patients with seizures, 18.2% were generalized, 27.1% were focal, and 18.6% were unknown. Overall, 25.8% of the EEGs were abnormal. However, in patients with a history of predisposing conditions for epileptic seizures or encephalopathies, the tracing was abnormal in 47.5%. The most frequent alteration on the abnormal EEGs was generalized slowing (18.2%). The EEG was useful in 76.7% of patients: AEDs changed in 8.4% and clinical management changed in 76.2% of patients. The usefulness of EEGs associated with acute ischemic lesions on CT (p = 0.023) and with the diagnosis of vasovagal syncope (p = 0.022). Routine EEG is useful in the ED, even in patients with a normal CT or MR brain image, because it helps determine clinical management or AED changes.

Frequency of antiepileptic drugs and response change in pediatric patients receiving 2 or more antiepileptic drugs.

Objectives:To investigate the frequency of changes in antiepileptic drugs (AEDs) use, as well as concomitant changes in the degree of seizure control in pediatric patients, who are receiving 2 or more AEDs.Methods:A prospective follow-up study at Jordan University Hospital’s pediatric neurology clinics was conducted on epileptic pediatric patients receiving at least 2 AEDs between December 2013 and April 2014. Patients were followed for 12 months.Results:A total of 82 patients were included, with a mean age of 7.2±4.7 years. The mean number of AEDs received by patients at enrollment was 2.4±0.6, and 2.5±0.7 after follow-up. Most patients (63.4%) experienced no change in seizure control, and the majority reported at least one adverse drug reaction. Most patients received lower doses than recommended, both at the beginning and end of the study. During the year, only 3 patients (4%) were eligible for dose tapering, which would then be converted to monotherapy. Follow-up appointments average was 4.2±2.9 visits/patients in one year. The frequency of medication changes and dose adjustment was very low, about one-third (29.3%) of patients requiring no change in AEDs during any follow-up visits.Conclusion:During the one year follow-up study, most patients on polytherapy maintained their level of response to the AEDs, with minimal changes in their regimen despite frequent follow-up visits. Only a small percent could be converted to AEDs monotherapy.

Ultra-long-term subcutaneous home monitoring of epilepsy-490days of EEG from nine patients.

ObjectiveTo explore the feasibility of home monitoring of epilepsy patients with a novel subcutaneous electroencephalography (EEG) device, including clinical implications, safety, and compliance via the first real‐life test.MethodsWe implanted a beta‐version of the 24/7 EEG SubQ (UNEEG Medical A/S, Denmark) subcutaneously in nine participants with temporal lobe epilepsy. Data on seizures, adverse events, compliance in using the device, and use of antiepileptic drugs (AEDs) were collected. EEG was recorded for up to 3 months, and all EEG data were reviewed visually to identify electrographic seizures. These were descriptively compared to seizure counts and AED changes reported in diaries from the same period.ResultsFour hundred ninety days of EEG and 338 electrographic seizures were collected. Eight participants completed at least 9 weeks of home monitoring, while one cancelled participation after 4 weeks due to postimplantation soreness. In total, 13 cases of device‐related adverse events were registered, none of them serious. Recordings obtained from the device covered 73% of the time, on average (range 45%‐91%). Descriptively, electrographic seizure counts were substantially different from diary seizure counts. We uncovered several cases of underreporting and revealed important information on AED response. Electrographic seizure counts revealed circadian distributions of seizures not visible from seizure diaries.SignificanceThe study shows that home monitoring for up to 3 months with a subcutaneous EEG device is feasible and well tolerated. No serious adverse device‐related events were reported. An objective seizure count can be derived, which often differs substantially from self‐reported seizure counts. Larger clinical trials quantifying the benefits of objective seizure counting should be a priority for future research as well as development of algorithms for automated review of data.

Eficacia y seguridad a largo plazo de la estimulación del nervio vago: Reporte preliminar en pacientes adultos con epilepsia focal fármacorresistente.

Objetivo: Reportar la experiencia en eficacia y seguridad a largo plazo de la estimulación del nervio vago (ENV), en una serie de pacientes adultos con epilepsia focal fármacorresistente, tratados en un hospital del Seguro Social del Perú. Material y Métodos: Se revisó la base de datos de la Unidad de Epilepsia de Adultos del Hospital Nacional Edgardo Rebagliati, de junio 2016 a junio 2019, a efecto de identificar pacientes a quienes se había implantados el estimulador. Se registraron las características clínicas y de manejo de la epilepsia (i.e., frecuencia de las crisis y regímenes de antiepilépticos (DAE), previas al implante, a los 3 y 6 meses del mismo y al final del periodo de seguimiento. Igualmente, el cambio porcentual promedio en la frecuencia de crisis en cada periodo, analizándose las tasas de respuesta ≥ 50%, ≥75% y los cambios en DAE, así como los efectos adversos al final del periodo de seguimiento. Resultados: Cinco pacientes con epilepsia multifocal fármacorresistente recibieron implante de ENV por no ser candidatos a cirugía resectiva de epilepsia. La edad promedio fue de 20,6 años, el promedio de duración del seguimiento fue de 21 meses y el promedio porcentual en la reducción de frecuencia de las crisis a los 3 meses, 6 meses y al final del seguimiento (21 meses) fue de 24%, 45% y 69%, respectivamente. Las tasa de respuesta ≥ 50% y ≥ 75%, fueron 80% y 40%. Se evidenció una reducción parcial de DAE en solo 1 paciente. El principal efecto adverso fue la ronquera. Conclusiones: La experiencia con ENV, reportada por primera vez en el Perú, demuestra su eficacia como terapia paliativa y un buen perfil de seguridad en adultos con epilepsia multifocal fármacorresistente. La eficacia es significativamente mayor con la estimulación sostenida a largo plazo.

Estimating Long-Term Vagus Nerve Stimulation Effectiveness: Accounting for Antiepileptic Drug Treatment Changes

To investigate the effectiveness of vagus nerve stimulation (VNS) in combination with pharmacological therapy in a longitudinal retrospective study at a single center. Data from 130 consecutive patients implanted with a VNS device between the years 2000 and 2013 was analyzed. Seizure frequency and pharmacological antiepileptic drug (AED) treatments were recorded prior to as well as at one, two, and five years after VNS implantation. Median age at epilepsy onset was five years and mean years from diagnosis to VNS implantation was 16.5 years. There was a significant seizure reduction overall (all p < 0.001). The responder (≥50% seizure frequency reduction) rate increased from 22.1 to 43.8% between the first and fifth year for the cohort as a whole, with the largest increase between the first and second year (22.1-38.1%) and regardless of AED changes. VNS effectiveness did not differ between patients who altered or remained on the same AEDs. Patients were treated with a median of three AEDs throughout the study and the number of AEDs significantly increased after two (p = 0.007) and five (p = 0.001) years. VNS is a well-tolerated palliative neuromodulatory treatment for drug resistant epilepsy with a 43.8% seizure reduction after five years. Our data supports the idea that VNS effectiveness increases with time. Therefore we suggest that VNS should be evaluated for at least two years after implantation. AED changes should try to be kept to a minimum during evaluation in order to determine the effectiveness of VNS.

Do Anti-Epileptic Drug modifications after first trimester of pregnancy influence fetal malformation or cognitive outcome?

ObjectiveThe management of Women With Epilepsy (WWE) in pregnancy is a challenge that demands balancing the risks of Major Congenital Malformation (MCM) on one hand with adequate seizure control on the other. While most studies have analysed the risks of Anti-Epileptic Drugs (AED) exposure in the first trimester, AED changes during the second and third trimester and their effects on fetal outcome has not been studied adequately. Materials and MethodsData of WWE who were prospectively followed up and completed pregnancy with live birth under the Kerala registry of epilepsy and pregnancy (KREP) between 1998 and 2014 were analysed. The AED addition, dose escalation, unchanged continuation, dose reduction or stoppage during the second or third trimester in comparison to the first trimester was tabulated for each drug. The outcome measures evaluated were malformation status and Developmental Quotient (DQ) at one year as extracted from the clinical records of the registry. ResultsThe first trimester AED exposure was nil for 231, monotherapy for 925 and polytherapy for 391 WWE. WWE on monotherapy in first trimester were more likely to remain on the same number of AEDs in second or third trimester than those who were on polytherapy (OR 3.1, 95% CI 2.2 – 4.46). AED naïve women had a higher likelihood (OR 16.7; 95% CI 10.9–25.8) of being started on AED than women on monotherapy being switched to polytherapy. At least one AED was reduced or stopped during second or third trimester more often in women on polytherapy (15.1%) than in women on monotherapy (3.7%) (OR 4.7; 95% CI 2.9–7.2). Malformation rates for the infants of women whose AED dosage was increased or added were not significantly different from those of others. There was no statistically significant change in DQ with increase in dose or addition of drugs in the second or third trimester. ConclusionAEDs were reduced in a significant proportion of patients on polytherapy while more than a third of women who were not on AEDs in the first trimester were subsequently started on AEDs. Increase in dose or addition of AEDs after the first trimester is unlikely to influence malformation outcome but the potential adverse effect on the DQ needs to be explored on a larger set of data.

Ranking the Leading Risk Factors for Sudden Unexpected Death in Epilepsy.

Sudden unexpected death in epilepsy (SUDEP) is rare in well-controlled epilepsy. However, SUDEP is a common cause of death in drug-resistant epilepsy. Over the last 30 years, multiple cohort and population studies have identified clinical risk factors associated with an increased risk for SUDEP. To identify and rank the leading SUDEP risk factors from major cohort and population-based studies. The incidence of SUDEP is also evaluated in special clinical situations, including antiepileptic drug treatment, epilepsy surgery, devices, and assignment to placebo in clinical trials. A PubMed search for English language human cohort studies for the terms Sudden, Death, and Epilepsy was performed for the years 1987-2017. Risk factors for SUDEP were identified and ranked by the weighted log adjusted odds ratio (OR)/relative risk ratio (RR). The top 10 leading risk factors ranked from highest to lowest log adjusted OR/RR are the following: ≥3 GTC seizures per year; ≥13 seizures in the last year; No Antiepileptic Drug (AED) treatment; ≥3 AEDs; ≥3 GTCs in the past year; 11-20 GTC seizures in the last 3 months; age of onset 0-15 years old; IQ < 70; 3-5 AED changes in the last year; ≥3 AEDs. Two risk factors from separate sources (≥3 GTC seizures and ≥3 AEDs) occur twice in the top 10 risk factors. The top 10 risk factors for SUDEP are identified and ranked. A ranking of the top risk factors could help clinicians identify patients at highest risk for SUDEP.

Patient emotions and perceptions of antiepileptic drug changes and titration during treatment for epilepsy.

To investigate the impact of antiepileptic drug (AED) change and dose titration on the emotional well-being of patients with epilepsy. Members of an online epilepsy community were invited to voluntarily participate in an online survey. The cross-sectional anonymous survey consisted of 31 multiple choice questions balanced in terms of variety and positivity/negativity of emotions concerning participants' most recent AED change. To substantiate survey results, spontaneous comments from epilepsy-related online forums and social media websites that mentioned participants' experiences with AED medication changes (termed passive listening statements) were analyzed and categorized by theme. All 345 survey participants (270 [78.3%] female; 172 [49.9%] were 26-45years old) self-reported an epilepsy/seizure diagnosis and were currently taking seizure medication; 263 (76.2%) were taking ≥2 AEDs and 301 (87.2%) had ≥1 seizure in the previous 18months. All participants reported a medication change within the previous 12months (dose increased [153 participants (44.3%)], medication added [105 (30.4%)], dose decreased [49 (14.2%)], medication removed [38 (11.0%)]). Improving seizure control (247 [71.6%]) and adverse events (109 [31.6%]) were the most common reasons for medication change. Primary emotions most associated (≥10% of participants) with an AED regimen change were (before medication change; during/after medication change) hopefulness (50 [14.5%]; 43 [12.5%]), uncertainty (50 [14.5%]; 69 [20.0%]), and anxiety (35 [10.1%]; 45 [13.0%]), and were largely due to concerns whether the change would work (212/345 [61.4%]; 180/345 [52.2%]). In the text analysis segment aimed at validating the survey, 230 participants' passive listening statements about medication titration were analyzed; additional seizure activity during dose titration (93 [40.4%]), adverse events during titration (71 [30.9%]), higher medication dosages (33 [14.3%]), and drug costs (25 [10.9%]) were the most commonly noted concerns. Although the emotional well-being of patients with epilepsy is complex, our study results suggest that participants report their emotional well-being as negatively affected by changes in AED regimen, with most patients reporting uncertainty regarding the outcome of such a change. Future research is warranted to explore approaches to alleviate patient concerns associated with AED medication changes.

Withdrawal of valproic acid treatment during pregnancy and seizure outcome: Observations from EURAP.

Based on data from the EURAP observational International registry of antiepileptic drugs (AEDs) and pregnancy, we assessed changes in seizure control and subsequent AED changes in women who underwent attempts to withdraw valproic acid (VPA) during the first trimester of pregnancy. Applying Bayesian statistics, we compared seizure control in pregnancies where VPA was withdrawn (withdrawal group, n = 93), switched to another AED (switch group, n = 38), or maintained (maintained-therapy group, n = 1,588) during the first trimester. The probability of primarily or secondarily generalized tonic-clonic seizures (GTCS) was lower in the maintained-therapy group compared with the other two groups, both in the first trimester and for the entire duration of pregnancy. GTCS were twice as common during pregnancy in the withdrawal (33%) and switch groups (29%) compared with the maintained-treatment group (16%). Limitations in the data and study design do not allow to establish a cause-effect relationship between treatment changes and seizure outcome, but these observations provide a signal that withdrawal of, or switch from, VPA during the first trimester could lead to loss of seizure control, and highlight the need for a specifically designed prospective observational study.

Anti-epileptic drug changes and quality of life in the community

Changes in anti-epileptic drug (AED) regimens may indicate unsatisfactory treatment results such as insufficient seizure control or adverse effects. This inference underlies epilepsy management and research, yet current studies often do not account for AED changes. We assessed AED change patterns and their association with quality of life (QoL), as main outcome measure, in a community-based setting. We assessed a cohort of 248 people with epilepsy identified from community pharmacy records from whom we retrieved AED dispensing history. We assessed all changes in AED use during the 2 years prior to the index date and current QoL using the validated Dutch QOLIE-31 questionnaire. Thirty-one per cent had at least one AED change during the study period, either in drug type or dose. People who changed showed significantly lower QoL (QOLIE score 73 vs 79), especially those who intensified their treatment. Each additional change was associated with a further reduction of 4.9 points in QoL score. AED changes are common practice, even in people with long-standing epilepsy. Frequent changes, as objective measure of epilepsy severity, are associated with a progressively lower QoL. Changes, even in dose, should be monitored in daily clinical practice and used as a red flag that may require adjustments in epilepsy management. This may include earlier referral to a specialized centre for a more thorough evaluation or counselling. AED changes can also be used as an outcome marker in epilepsy research as a proxy of QoL for better translation of drug-efficacy results to general practice.

Vagus nerve stimulation and late-onset bradycardia and asystole: Case report

Vagus nerve stimulation (VNS) therapy is approved in the United States by the FDA in 1997 for medically refractory partial epilepsy in patients of ages 12 years and above. The most common stimulation-associated side effects are voice alteration, hoarseness, throat and neck pain, headache, cough, and dyspnea. Four patients with VNS had late-onset bradycardia and asystole, attributed to VNS stimulation. Their ages were 13, 17, 47, and 55. Cardiac symptoms were noted after 2.33–9 years postimplantation [1–4]. Three cases had symptoms correlated with stimulation, monitored by electrocardiogram [1,2,4]. This new case report highlights cardiac syncope with very similar clinical presentation as previous four cases, and raises the concern for cardiac symptoms, even many years after VNS implantation.

Pharmacology aspects during transition and at transfer in patients with epilepsy.

Contrary to the treatment concerns regarding drug compliance or pregnancy at transition to adulthood, those directly related to epilepsy remain poorly documented. As an initial step to answer this problem, we reviewed the controlled trials of antiepileptic drugs (AEDs) independently performed in adults and children for a given syndrome. Then we reviewed the longitudinal long-term course in the various epilepsy syndromes. Optimizing AED treatment at adulthood might be beneficial, even after many years of pharmacoresistance. Finally we retrospectively reviewed our personal series of 39 patients with specific pharmacoresistant epilepsy syndromes, who transferred from pediatric to adult care between 2005 and 2012. In 26 of the patients, AEDs were modified and, we reduced seizure frequency in 62% of them, including highly refractory patients. By contrast, AED changes in six controlled patients (for pregnancy anticipation or vigabatrin-related retinal toxicity) led to severe seizure relapse. Further studies are needed to elaborate guidelines in pharmacoresistant syndromes during transition and after transfer to adult care.

Comparison of risk factors for pediatric convulsive status epilepticus when defined as seizures ≥5 min versus seizures ≥30 min

PurposeTo identify risk factors (RF) of pediatric convulsive status epilepticus (SE) and to determine whether defining SE as seizures ≥5min (SE5) or seizures ≥30min (SE30) would modify the risk factors identified. MethodsRetrospective case–control study. We included patients 1 month to 21 years of age at the time of convulsive SE. We compared the characteristics of patients with SE (cases) versus those without SE (controls) using two different seizure duration thresholds: 5min and 30min. Results1062 patients (54% males) were enrolled. The median (p25–p75) age at the episode was 6.4 (2.8–11.8) years. 444 (41.8%) patients had SE5 and 149 (14%) patients had SE30. On univariate analysis, risk factors for SE were not markedly different when considering a 5 or 30min threshold. Compared to their respective controls patients with both SE5 and SE30 were younger at the age of seizure onset and at the age of SE, were on more antiepileptic drugs (AEDs) at baseline, had a higher rate of changes in AEDs in the three months prior to the episode, were more likely to have developmental delay at baseline, and a higher mortality rate. A higher baseline seizure frequency, and a higher increase in seizure frequency prior to the index episode were seen only in SE5. ConclusionThis series identifies RF which predict convulsive SE in pediatric patients. These RF are similar when considering a 5min or a 30min threshold for the definition of SE.

Reducing versus stopping antiepileptic medications after temporal lobe surgery.

ObjectiveTo study the safety of antiepileptic drug (AED) withdrawal after temporal lobe epilepsy (TLE) surgery.MethodsWe reviewed patients who underwent TLE surgery from 1995 to 2011, collecting data on doses, dates of AED initiation, reduction, and discontinuation. Predictors of seizure outcome were defined using Cox-proportional hazard modeling and adjusted for, while comparing longitudinal seizure-freedom in patients for whom AEDs were unchanged after resection as opposed to reduced or stopped.ResultsA total of 609 patients (86% adults) were analyzed. Follow-up ranged from 0.5 to 16.7 years. Most (64%) had hippocampal sclerosis. Overall, 229 patients had remained on their same baseline AEDs, while 380 patients stopped (127 cases) or reduced (253 cases) their AEDs. Mean timing of the earliest AED change was shorter in patients with recurrent seizures (1.04 years) compared to those seizure-free at last follow-up (1.44 years; P-value 0.03). Whether AEDs were withdrawn 12 or 24 months after surgery, there was a 10–25% higher risk of breakthrough seizures within the subsequent 2 years. However, 70% of patients with seizure recurrence after AED discontinuation reachieved remission, as opposed to 50% of those whose seizures recurred while reducing AEDs (P = 0.0001). Long-term remission rates were similar in both AED discontinuation and “unchanged” groups (82% remission for AEDs withdrawn after 1 year and 90% for AEDs withdrawn after 2 years), while only 65% of patients whose recurrences started during AED reduction achieved a 2-year remission by last follow-up.InterpretationAED withdrawal increases the short-term risk of breakthrough seizures after TLE surgery, and may alter the long-term disease course in some patients.

Uninformed clinical decisions resulting from lack of adherence assessment in children with new-onset epilepsy

This study examined the relationship between nonadherence to antiepileptic drug (AED) therapy and clinical decision making in a cohort of 112 children with newly diagnosed epilepsy. Antiepileptic drug adherence was monitored using electronic monitoring over the first six months of therapy. The primary outcome measure was rate of uninformed clinical decisions as defined by the number of participants with AED dosage or drug changes to address continued seizures who demonstrated nonadherence prior to the seizure. Among the 52 (47%) participants who had an AED change for continued seizures, 30 (27% of the overall cohort) had imperfect medication adherence prior to their seizures. A quarter of the children with new-onset epilepsy had uninformed medication changes because adherence was not rigorously assessed in clinical practice. The results highlight the importance of routinely assessing medication adherence in this population.

Is antiepileptic drug use related to depression and suicidal ideation among patients with epilepsy?

Depression and suicide are increased in patients with epilepsy. The U.S. Food and Drug Administration warns that antiepileptic drugs (AEDs) are associated with increased risk of suicidality. This study examines the relationship among depression, suicidal ideation, and AEDs in a prospective cohort of 163 patients with epilepsy from a registry at the University of Florida (January 2006 to August 2008). The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) was used to measure mood and suicidal ideation across two time points (median = 154 days). Groups included: (1) No AED Change, (2) New AED Added, (3) AED Dose Increased, (4) AED Reduced/Stopped, (5) Multiple AED Changes, and (6) Combined Any AED Change (groups 2–5 combined). No group had worsening mood or suicidal ideation. Significant improvements in proportions of depression and suicidal ideation were seen only for the No AED Change group, which differed only with the AED Dose Increased group with respect to suicidal ideation.

Urgent Continuous EEG (cEEG) Monitoring Leads to Changes in Treatment in Half of Cases

How Seizure Detection by Continuous Electroencephalographic Monitoring Affects the Prescribing of Antiepileptic Medications. Kilbride RD, Costello DJ, Chiappa KH. Arch Neurol 2009;66(6):723–728. Objectives To assess the effect of continuous electroencephalographic monitoring on the decision to treat seizures in the inpatient setting, particularly in the intensive care unit. Design Retrospective cohort study. Setting Medical and neuroscience intensive care units and neurological wards. Patients Three hundred consecutive nonelective continuous electroencephalographic monitoring studies, performed on 287 individual inpatients over a 27-month period. Main Outcome Measures Epileptiform electroencephalographic abnormalities and changes in antiepileptic drug (AED) therapy based on the electroencephalographic findings. Results The findings from the continuous electroencephalographic monitoring led to a change in AED prescribing in 52% of all studies with initiation of an AED therapy in 14%, modification of AED therapy in 33%, and discontinuation of AED therapy in 5% of all studies. Specifically, the detection of electrographic seizures led to a change in AED therapy in 28% of all studies. Conclusions The findings of continuous electroencephalographic monitoring resulted in a change in AED prescribing during or after half of the studies performed. Most AED changes were made as a result of the detection of electrographic seizures.

How Seizure Detection by Continuous Electroencephalographic Monitoring Affects the Prescribing of Antiepileptic Medications

To assess the effect of continuous electroencephalographic monitoring on the decision to treat seizures in the inpatient setting, particularly in the intensive care unit. Retrospective cohort study. Medical and neuroscience intensive care units and neurological wards. Three hundred consecutive nonelective continuous electroencephalographic monitoring studies, performed on 287 individual inpatients over a 27-month period. Epileptiform electroencephalographic abnormalities and changes in antiepileptic drug (AED) therapy based on the electroencephalographic findings. The findings from the continuous electroencephalographic monitoring led to a change in AED prescribing in 52% of all studies with initiation of an AED therapy in 14%, modification of AED therapy in 33%, and discontinuation of AED therapy in 5% of all studies. Specifically, the detection of electrographic seizures led to a change in AED therapy in 28% of all studies. The findings of continuous electroencephalographic monitoring resulted in a change in AED prescribing during or after half of the studies performed. Most AED changes were made as a result of the detection of electrographic seizures.

Vagus nerve stimulation for 1 year in 269 patients on unchanged antiepileptic drugs

Purpose: To study, in patients on unchanged antiepileptic drugs (AEDs): (1) seizure rates after 3 and 12 months of vagus nerve stimulation (VNS); (2) effects of VNS parameters; (3) patient characteristics versus VNS responsiveness. Methods: We located in the VNS registry 269 patients treated for 1 year with no changes in AEDs. Seizure rates were calculated at 3 and 12 months. We analyzed: (1) 3 months versus 12 months seizure rates; (2) effects of changing duty cycles between 3 and 12 months; (3) effects of output current; (4) seizure rate changes associated with patient characteristics. Results: Seizure rates improved between 3 months (median=−45%) and 12 months (median=−58%) ( P<0.0001). There were no differences between patients who stayed on standard or rapid cycling, or changed from standard to rapid. Stimulation parameters did not affect seizure rates. VNS responsiveness was associated with older age ( P=0.016), longer duration epilepsy ( P=0.033), and syndromes other than Lennox–Gastaut ( P=0.003). Conclusions: This was an analysis of treatment outcomes, not a prospective clinical trial. Nonetheless, our results suggest: (1) seizure rates decline with increasing VNS duration; (2) this decline occurs without AED changes; (3) this decline is not due to changes in stimulation parameters; (4) patient characteristics predictive of VNS responsiveness remain elusive.

Video‐EEG evidence of lateralized clinical features in primary generalized epilepsy with tonic‐clonic seizures

Background Whether cortical or subcortical structures, specifically the thalamus, play the dominant role in generating primary generalized seizures has been the subject of long debate. Most experimental data implicate a hyperexcitable cortical generator of spike‐and‐wave activity, with the thalamus quickly recruited to sustain the generalized oscillations through a reverberating thalamocortical network. However, there is little clinical evidence to support the cortical generator hypothesis. We present video‐EEG recordings of generalized tonic‐clonic seizures in three patients with proven primary generalized epilepsy (PGE), all of whom showed a consistent pattern of lateralized seizure onset compatible with a focal frontal lobe generator. Methods Among 300 patients referred for video‐EEG monitoring for intractable epilepsy, three were found to have PGE with tonic‐clonic convulsions. All had a positive family history for epilepsy and no other epilepsy risk factors. Epilepsy onset was during adolescence (2/3) or childhood (1/3). Patients were taking 1‐4 antiepileptic drugs (AEDs) at admission, none of which was valproic acid. Results Interictal EEG showed very active, bilaterally synchronous generalized spike‐and‐wave or polyspike‐and‐wave discharges between 2.5‐4.5 Hz, maximal over the midfrontal structures symetrically in all patients. Ictal EEG showed generalized rhythmic activity without lateralization at seizure onset. Surprisingly, in all 6 recorded tonic‐clonic seizures there was a sustained (10‐15 seconds), stereotyped, clinical lateralization at onset, which took the form of a tonic “fencing posture” in one patient (two seizures) and forced head/eye/torso version in two patients (four seizures). Two patients became seizure‐free shortly after switching to valproate monotherapy. One patient refused valproate but has improved more than 90 % with a change in AEDs to lamotrigine and phenobarbital (follow‐up in all patients &gt; 18 months). Conclusions Tonic‐clonic seizures are presumed to be generalized from onset in patients with PGE. However, video‐EEG monitoring in these patients is rarely performed and the actual clinical features of the seizures may be underappreciated. The demonstration of sustained lateralization at onset in our patients, with features clinically indistinguishable from focal onset frontal lobe seizures, is compatible with the hypothesis of a focal region of cortical hyperexcitability situated in the frontal lobes of some patients with PGE. Whether this cortical generator is autonomous or “triggered” by ascending, possibly normal, thalamocortical volleys is unresolved. [Published with video sequences].