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.     

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.     

Marijuana use in adults admitted to a Canadian epilepsy monitoring unit

ObjectivesEpidemiologic evidence supporting antiseizure properties of cannabis is limited and controversial. We determined the prevalence of marijuana use and its perceived effects in patients with and without epilepsy.MethodsInformation was collected over 14 months from consecutive adult patients admitted to an epilepsy monitoring unit using a 27-item anonymous questionnaire. Patients with cognitive impairment unable to understand the questions or give informed consent and readmissions were not recruited. Subjects were divided into 4 groups, those with epileptic seizures, those with psychogenic nonepileptic seizures (PNES), those with both epileptic and PNES, and those with other nonepileptic events. Patients with exclusively epileptic seizures were compared with those with exclusively PNES.ResultsFrom 310 patients, 18 undiagnosed cases were excluded leaving a cohort of 292 patients with median age 35 (range: 27–49) years; 57.2% female. Epilepsy was documented in 190 (65.1%), PNES in 64 (21.9%), and both types of seizures in 26 (8.9%). Median duration of seizure disorder was longer (2 [1–9] vs. 13 [5.7–25] years; p < 0.001) and seizure frequency lower (daily or weekly in 62.3% vs. 44.9%; p = 0.03) in patients with epilepsy compared with those in patients with PNES. Overall, 166 (57%) had tried marijuana, and 36.2% used it over the past year. Utilization was 57.1% in sole epilepsy and 64.1% in sole PNES, but daily use was more likely in epilepsy (59% vs. 33.3%). Estimated mean dose was 1 g/day. Marijuana use was associated with tobacco smoking (p < 0.001) but not alcohol use. Eight patients used other street drugs. Improvement in seizures was perceived by 84% in those with epilepsy and 72.7% in those with PNES. In the 2 groups, stress was decreased in 84.9% and 88%, sleep improved in 77.3% and 88%, and memory/concentration was better in 32% and 28%, respectively. Antiepileptic drug side effects were decreased in 53.2% of marijuana users. Perceived effect on epileptic seizures correlated with effect on stress (r = 0.35, p = 0.004). Adverse effects of marijuana were mild and reported in 30.7% but included possible seizure precipitation in 5 patients with epilepsy.SignificancePatients with uncontrolled epilepsy or nonepileptic events had a high rate of marijuana use with associated perceived improvements in seizure control, stress, sleep, and drug side effects. Stress reduction may contribute to the perceived impact of marijuana on seizures and nonepileptic events in adults.     

Efficacy of verapamil as an adjunctive treatment in children with drug-resistant epilepsy: A pilot study

PurposeVerapamil, a voltage-gated calcium channel blocker, has been occasionally reported to have some effect on reducing seizure frequency in drug-resistant epilepsy or status epilepticus. We aimed to investigate the efficacy of verapamil as add-on treatment in children with drug-resistant epilepsy.MethodsSeven children with drug-resistant structural-metabolic, unknown or genetic (e.g., Dravet syndrome [DS]) epilepsy received verapamil as an add-on drug to baseline antiepileptic therapy. Verapamil was slowly introduced at the dosage of 1 mg/kg/day and titrated up to 1.5 mg/kg/day. After completing the titration period, patients entered a 14-month maintenance period and were followed up at 3, 8, and 14 months. Heart monitoring was performed at baseline and at each follow-up. The primary outcome measure was the response of seizures to verapamil.ResultsThree subjects with genetically determined DS showed a partial (reduction of 50–99%) response for all types of seizures. A patient with DS without known mutation showed a partial control of all types of seizures in the first 13 months; then seizures worsened and verapamil was suspended. Two patients with structural epilepsy and one with Lennox–Gastaut syndrome showed no improvement. Any side effects were recorded.ConclusionsAdd-on treatment with verapamil seems to have some effect in controlling seizures in patients with genetically determined DS. Our observations justify further research on the relationship between calcium channels, calcium channel blockers, and channelopathies.     

Impact of stigma on the quality of life of patients with refractory epilepsy

PurposeTo assess the impact of perceived stigma on the quality of life of Bulgarian patients with refractory epilepsy.MethodsWe studied 70 adult patients with refractory epilepsy, without cognitive impairment, progressive somatic, neurological disease or recent seizures, and 70 patients with pharmacosensitive epilepsy. All participants completed a 3-item stigma scale, the patients with refractory epilepsy also completed a Health Related Quality of Life measure (the QOLIE-89).ResultsThe patients with refractory epilepsy had a mean disease duration 25.1 ± 1.3 years. 40.0% of patients (±5.9) had symptomatic epilepsy. Seventeen patients (24.2% ± 5.1) had partial seizures, 16 (22.8% ± 5.0) had generalized seizures and 37 (52.9 ± 6.0) had a mixture of partial and generalized seizures. Most participants had several seizures per week (45.7%) or month (30.0%) despite the fact that 90% were taking combination antiepileptic drug treatment. We found perceived stigma in 43.6% of patients with refractory epilepsy, and 28.7% self-reported severe stigmatization. Only 4 (5.7%) patients with pharmacosensitive epilepsy reported stigmatization which was mild or moderate in all cases. Perceived stigma had a negative impact on the overall score of the QOLIE-89 (T-score 47.8), as well as on all subscales of QOLIE-89, with the exception of “change in health” and “sexual relations”. Patients with refractory epilepsy reporting stigmatization most commonly had very low and low scores on the subscales “health perceptions” (82.9%), “emotional well-being” (71.5%), “memory” (63.4%) and “health discouragement” (62.5%). There was a negative correlation of all QOLIE-89 subscales with perceived stigma severity.ConclusionAll aspects of the quality of life of Bulgarian patients with refractory epilepsy correlate negatively with the severity of perceived stigma.     

Psychogenic nonepileptic seizures in patients with surgically treated temporal lobe epilepsy: Presurgical and de novo postsurgical occurrence

Whether occurring before or after an epilepsy surgery, psychogenic nonepileptic seizures (PNES) impact treatment options and quality of life of patients with epilepsy. We investigated the frequency of pre- and postsurgical PNES, and the postsurgical Engel and psychiatric outcomes in patients with drug-resistant temporal lobe epilepsy (TLE). We reviewed 278 patients with mean age at surgery of 37.1 ± 12.4 years. Postsurgical follow-up information was available in 220 patients, with average follow-up of 4 years.Nine patients (9/278 or 3.2%) had presurgical documented PNES. Eight patients (8/220 or 3.6%) developed de novo PNES after surgery. Pre- and postsurgery psychiatric comorbidities were similar to the patients without PNES. After surgery, in the group with presurgical PNES, five patients were seizure-free, and three presented persistent PNES. In the group with de novo postsurgery PNES, 62.5% had Engel II–IV, and 37.5% had Engel I. All presented PNES at last follow-up.Presurgical video-EEG monitoring is crucial in the diagnosis of coexisting PNES. Patients presenting presurgical PNES and drug-resistant TLE should not be denied surgery based on this comorbidity, as they can have good postsurgical epilepsy and psychiatric outcomes. Psychogenic nonepileptic seizures may appear after TLE surgery in a low but noteworthy proportion of patients regardless of the Engel outcome.     

Prognosis of status epilepticus (SE): Relationship between SE duration and subsequent development of epilepsy

In animal models, SE duration is related to epileptogenesis. Data in humans are scarce, mainly in NCSE; therefore, we aimed to study the prognosis of SE de novo and which factors may influence subsequent development of epilepsy.MethodsWe evaluated patients with SE without previous epilepsy at our hospital (February 2011–February 2014), including demographics, etiology, number of AEDs, duration of SE, mortality, and occurrence of seizures during follow-up.ResultsEighty-nine patients were evaluated. Median age was 69 (19–95) years old. Among them, 33.7% were convulsive. Regarding etiology, 59 were considered acute symptomatic (41 lesions, 18 toxic–metabolic), 17 remote or progressive symptomatic, and 13 cryptogenic. The median recovery time was 24 h (30 min–360 h). In-hospital mortality was 29% (n = 26). After a median follow-up of 10 months, 58.7% of survivors (n = 37) showed seizures. Subsequently, we analyzed which factors might be related to the development of epilepsy, and we found that epilepsy development was more frequent with longer SE duration (37 vs. 23 h, p = 0.004); furthermore, patients with a toxic–metabolic etiology developed epilepsy less frequently (33% vs. 67%; p = 0.022). Epilepsy was also correlated (tendency) with focal SE (p = 0.073), a lesion in neuroimaging (p = 0.091), and the use of 2 or more AEDs (p = 0.098). Regarding SE duration, a cutoff of above 24 h was clearly related to chronic seizures (p = 0.014); however, combining etiology and duration, the association of longer SE and epilepsy was significant in acute lesional SE (p = 0.034), but not in epilepsy with cryptogenic or remote/progressive etiology. After a logistic regression, only a duration longer than 24 h (OR = 3.800 (1.277–11.312), p = 0.016) was found to be an independent predictor of the development of epilepsy.ConclusionIn patients with SE, the longer duration is associated with an increased risk of subsequent epilepsy at follow-up, mainly in symptomatic SE due to an acute lesion. It is unclear if it might be the result of a more severe injury causing both prolonged seizures and subsequent epilepsy, and therefore whether more aggressive treatment in this group might avoid this possibility. Most of the patients with cryptogenic or remote/progressive SE developed epilepsy regardless of SE duration.This article is part of a Special Issue entitled “Status Epilepticus”.     

Predicting drug resistance in adult patients with generalized epilepsy: A case–control study

ObjectivesUsing an adult cohort of patients with generalized epilepsy, we aimed to identify risk factors for development of drug-resistant epilepsy (DRE), which if identifiable would allow patients to receive earlier treatment and more specifically individualized treatment plans.MethodsFor the case–control study, 118 patients with generalized epilepsy (GE) between the ages of 18 and 75 were included after selection from a database of 800 patients referred from throughout the Saskatchewan Epilepsy Program. Definitions were used in accordance with ILAE criteria. The odds ratio and its confidence interval were calculated. We performed a logistic regression analysis.ResultsForty-four (37%) patients fulfilled the definition of DRE (cases), and seizures in 74 (63%) patients were not intractable (controls). Patients with DRE were significantly younger than the controls at the onset of epilepsy (6.6 vs. 18.8 years, p = < 0.001). Significant variables on univariate analysis were the following: epilepsy diagnosed prior to 12 years (OR: 12.1, CI: 4.8–29.9, p < 0.001), previous history of status epilepticus (OR: 15.1, CI: 3.2–70.9, p < 0.001), developmental delay (OR: 12.6, CI: 4.9–32, p < 0.001), and cryptogenic epilepsy (OR: 10.5, CI: 3.9–27.8, p < 0.001). Our study showed some protective factors for DRE such as a good response to first AED, idiopathic etiology, and history of febrile seizures. In the logistic regression analysis, two variables remained statistically significant: developmental delay and more than one seizure type.ConclusionOur study has identified a set of variables that predict DRE in patients with generalized epilepsy. Risk factors identified in our study are similar to those previously identified in pediatric studies, however, our study is specifically tailored to adult patients with generalized epilepsy.     

Vagus nerve stimulation in pediatric patients: Is it really worthwhile?

Vagus nerve stimulation (VNS) seems to be effective in the management of selected cases of pharmacoresistant epilepsy in children. This was a case–control prospective study of children with refractory epilepsy submitted to vagal nerve stimulator implantation and a control group with epilepsy treated with antiepileptic drugs. Patients under 18 years of age who underwent clinical or surgical treatment because of pharmacoresistant epilepsy from January 2009 to January 2012 were followed and compared with an age-matched control group at final evaluation. Statistically significant differences were observed considering age at epilepsy onset (VNS group — 1.33 ± 1.45 years; controls — 3.23 ± 3.11; p = 0.0001), abnormal findings in neurological examination (p = 0.01), history of previous ineffective epilepsy surgery (p = 0.03), and baseline seizure frequency (p = 0.0001). At long-term follow-up, 55.4% of the patients in the VNS group had at least 50% reduction of seizure frequency, with 11.1% of the patients presenting 95% reduction on seizure frequency. Also, a decrease in traumas and hospitalization due to seizures and a subjective improvement in mood and alertness were observed. The control group did not show a significant modification in seizure frequency during the study. In this series, VNS patients evolved with a statistically significant reduction of the number of seizures, a decreased morbidity of the seizures, and the number of days in inpatient care. In accordance with the current literature, VNS has been proven to be an effective alternative in the treatment of pediatric patients with drug-resistant epilepsy.     

Prognostic significance of acute postoperative seizures in extra-temporal lobe epilepsy surgery

ObjectiveThis study aims to assess the prognostic value of acute postoperative seizures (APOS) in patients surgically treated for drug-resistant extra-temporal lobe (ET) epilepsy.MethodsWe studied 77 consecutive patients with ET epilepsy who underwent epilepsy surgery and were followed up for at least 2 years (mean duration of follow-up 6.2 years, range 2–14). Medical charts were reviewed to identify APOS, defined as ictal events with the exception of auras occurring within the first 7 days after surgery. Seizure outcome was determined at annual intervals. Patients who were in Engel Class I at the last contact were classified as having a favourable outcome.ResultsSeizure outcome was favourable in 47 patients (61%). The occurrence of APOS and incompleteness of resection were found to be independently associated with unfavourable outcome in a multiple regression model including all preoperative factors identified as outcome predictors in univariate analysis. Duration of illness was the only independent preoperative predictor of APOS.ConclusionsOur study suggests that APOS may predict long-term outcome in patients undergoing resective surgery for ET epilepsy. Given some study limitations, our findings should be regarded as preliminary and need confirmation from future larger, prospective, multicentre studies.SignificanceCaution may be required in the clinical management of patients experiencing APOS.     

IDH1 and IDH2 mutations in postoperative diffuse glioma-associated epilepsy

ObjectiveIsocitrate dehydrogenase 1 and 2 mutations (IDH1/2) have an established association with preoperative seizures in patients with grades II–IV diffuse gliomas. Here, we examined if IDH1/2 mutations are a biomarker of postoperative seizure frequency.MethodsThis was a retrospective study. Patients with grades II–IV supratentorial diffuse glioma, immunohistochemistry results of IDH1-R132H, and antiepileptic drug (AED) prescribed postoperatively were included. The primary outcome was seizure frequency over the first 12 postoperative months: Group A — postoperative seizure freedom; Group B — 1–11 seizures over 12 months (less than one seizure per month); and Group C — greater than one seizure per month. Rates of IDH1-R132H mutation were compared between the three outcome groups in univariate and multivariate analyses. Subgroup analysis was performed in 64 patients with IDH1/2 pyrosequencing data.ResultsOne hundred cases were included in the analysis: 30.0% grade II, 20.0% grade III, and 50.0% grade IV gliomas. Group B patients averaged 1 seizure over 12 months, compared with 2 seizures per month in Group C. Isocitrate dehydrogense 1-R132H mutation was present in 29.3% (17/58) of Group A, 18.2% (14/22) of Group B, and 70.0% (14/20) of Group C patients (p = 0.001). On multivariate analysis, after controlling for preoperative seizure, grade, and temporal tumor location, IDH1-R132H was associated with Group C when compared with both Group A (RR 4.75, p = 0.032) and Group B (RR 9.70, p = 0.012). In the subgroup with IDH1/2 molecular data, an IDH1/2 mutation was present in 64.7% (22/34) of Group A, 28.6% (4/14) of Group C, and 87.5% (14/16) of Group C patients (p = 0.004).SignificanceIn patients with supratentorial diffuse gliomas, IDH1-R132H mutations are associated with a more severe phenotype of postoperative epilepsy. These findings support further research into IDH mutations, and the potential for an antiepileptic therapeutic effect of their inhibitors, in patients with glioma-associated epilepsy.     

Epilepsy in neurofibromatosis type 1

ObjectivesTo describe the characteristics of epilepsy in patients with Neurofibromatosis type 1 (NF1).MethodsAnalysis of a cohort of consecutive NF1 patients seen in our NF1 clinic during a three-year period.ResultsOf the 184 NF1 patients seen during that period, 26 had epilepsy and three had febrile seizures. Of the 26, 17 (65%) had localization-related epilepsy, seven of whom (41%) were drug resistant. Six (23%) had apparently primary generalized epilepsy (0/6 drug resistant), two (8%) Lennox-Gastaut syndrome, and one (4%) West syndrome (all three were drug-resistant). As compared to the patients with no epilepsy, those with epilepsy were more likely to have MRI findings of mesial temporal sclerosis (MTS) (23% vs. 5%, p = 0.0064), and cerebral hemisphere tumors (31% vs. 10%, p = 0.0079), but not of the other MRI findings including neurofibromatosis bright objects, or optic gliomas. Three of the six patients with MTS underwent temporal lobectomy with subsequent control of their seizures with confirmation of MTS on pathology in 3/3 and presence of coexisting focal cortical dysplasia (FCD) in 2/3. We also have observed three additional patients outside the above study with the association of NF1, MTS, and intractable epilepsy.SignificanceEpilepsy is relatively common in NF1, often occurs in patients with brain tumors or with MTS which can coexist with FCD, can be associated with multiple types of epilepsy syndromes, and when localization-related is often drug-resistant. Patients with NF1 and MTS can respond to medial temporal lobectomy and may have coexisting medial temporal lobe cortical dysplasia.     

Postsurgical outcome in patients with olfactory auras and drug-resistant epilepsy

ObjectivesWe investigated the clinical features associated with olfactory auras in patients with drug-resistant epilepsy and also hypothesized that this type of aura may predict worse postsurgical outcome in patients with drug-resistant temporal lobe epilepsy (TLE).MethodsIn this retrospective analysis, data from all patients with drug-resistant epilepsy who underwent epilepsy surgery were reviewed. Patients were prospectively registered in a database from 1986 through 2016. We assessed outcome in the first 5 years after surgery to produce a Kaplan–Meier estimate of seizure recurrence. Post-surgical outcome was classified into two groups; 1) seizure-free, with or without auras; or 2) relapse of complex partial or secondarily generalized seizures. We also investigated the clinical features of patients with TLE and olfactory auras compared with those without olfactory auras.ResultsWe studied 1186 patients. Thirty-seven patients (3.1%) reported olfactory auras with their seizures. Thirty-two patients had temporal lobe surgery. Intracranial video-EEG recording was performed in four patients. Three patients with lateral temporal neocortical seizures reported olfactory auras with their seizures; two of them were seizure-free after surgery. There were no significant clinical differences between patients with TLE and olfactory auras compared with those without. Seizure outcome after surgery was not significantly different between these two groups (p = 0.3; Cox–Mantel test).ConclusionThe rarity of olfactory auras makes it difficult to propose new diagnostic and treatment strategies. A multicenter approach, which can enroll more patients, is needed to devise better therapies for patients with drug-resistant epilepsy and this symptom.     

Differences in quality of life of women and men with drug-resistant epilepsy in Poland

PurposeThe aim of the study was to assess the differences in health-related quality of life in groups of men and women suffering with drug-resistant epilepsy and to determine which factors influence quality of life.MethodsThe examined group consisted of 64 subjects with drug-resistant epilepsy — 31 men and 33 women. The mean duration of epilepsy was 17.56 ± 8.92 and 19 ± 9.56 years, respectively. The following diagnostic tools were used: QOLIE-31-P, Wechsler Adult Intelligence Scale — Revised (WAIS-R (PL)), and Hamilton Rating Scale for Depression (HRSD).ResultsScores in QOLIE-31-P did not differ significantly between groups of men and women with drug-resistant epilepsy; however, a more detailed analysis revealed certain disparities. Multiple regression analyses indicated that some distinct factors were associated with quality of life in each sex. In the group of women, there were no significant predictors of their quality of life. Among the group of men, depression intensity was the only statistically significant QoL predictor, explaining 16% of the variance (adjusted R² = 0.16, F(6, 24) = 19.7, p < 0.01). Moreover, patients with depression had lowered scores in the Emotional Well-Being and Energy/Fatigue subscales, regardless of the sex.ConclusionThe study revealed that, despite similar scores in QOLIE-31-P, specific factors may differentially affect the quality of life of men and women with drug-resistant epilepsy in Poland. Nevertheless, replication of these results with a larger number of participants is needed for a more definitive conclusion.     

Areca catechu (palm tree) nut chewing and seizures: An observational study

ObjectiveThe objective of this study was to report the impact of chronic abuse of Areca catechu nut wrapped in leaf (also known as doma, quid, paan), the fourth most commonly abused psychoactive substance worldwide, on the frequency of seizures among people with epilepsy.MethodsPeople with clinically diagnosed epilepsy (> 14 years old) residing in the Kingdom of Bhutan were surveyed for self-reported Areca catechu use, demographic variables, epilepsy characteristics, and seizure frequency. The relationship between seizure frequency in the prior month and chewing Areca catechu, adjusted for various confounders, was analyzed using multivariable regression models.ResultsThere were 152 people with epilepsy, including 50 chewers (33%) and 102 (67%) nonchewers. The median duration of chewing A. catechu was 62 months (25th, 75th percentiles: 24, 120 months). Chewers consumed an average of three nuts daily. There was no significant difference between chewers and nonchewers in the mean age, proportion of male vs. female, age at first epileptic seizure, or number of antiepileptic drugs presently taken; chewers were more likely to be rural dwellers (p = 0.042). After adjustment for all of the above variables, on average, chewers had 58.7% fewer [95%CI: (− 79.4, − 17.0)] seizures in the prior month, equating to 2.1 fewer [95% CI: (− 3.9, − 0.3)] seizures.ConclusionsOur observational study suggests that the social custom of chewing Areca catechu nut is associated with reduced seizure frequency among people with epilepsy. This association may be due to its natural stimulant properties, a novel antiepileptic property of the nut, or has another, yet unknown explanation.     

Management of focal epilepsy in adults treated with polytherapy in France: The direct cost of drug resistance (ESPERA study)

PurposeTo estimate the direct costs associated with the current management of focal epilepsy in adults treated with a combination of antiepileptic drugs (AEDs) in France and the supplementary costs of drug resistant epilepsy as defined by the International League Against Epilepsy (ILAE) in 2009.MethodsESPERA was a multicentre, observational, cross-sectional study conducted in France in 2010. A random sample of neurologists, including specialists in epilepsy, prospectively enrolled adults with focal epilepsy treated with a combination of AEDs. Investigators classified their patients according to the 2009 ILAE criteria for drug resistance and this classification was then reviewed by two experts. All items of healthcare resource use associated with epilepsy over the previous year were documented retrospectively and valued from a societal perspective.ResultsSeventy-one neurologists enrolled 405 patients. After experts’ review, 70.6% of patients were classified with drug-resistant epilepsy, 22.4% with drug-responsive epilepsy and 7% with undefined epilepsy. The mean annual epilepsy-related direct costs per patient were €4485 ± €4313 in patients with drug-resistant epilepsy compared to €1926 ± €1795 in patients with drug-responsive epilepsy. In these two groups, costs of AEDs were estimated at €2603 and €1544, respectively. Patients with drug-resistant epilepsy were more often hospitalised (mean annual cost: €1270 vs. €97) and underwent more additional tests (mean annual cost: €194 vs. €53).ConclusionThe direct cost of focal epilepsy in adults on AED combinations was estimated at €3850/patient/year. Drug resistance, as defined by the 2009 ILAE criteria, resulted in significant extra costs which varied with seizure frequency.     

Evaluation of health-care utilization in patients with Dravet syndrome and on adjunctive treatment with stiripentol and clobazam

Dravet syndrome (DS) is a rare, severe childhood epilepsy syndrome that imposes a substantial burden on patients and their caregivers. This study evaluated health-care utilization over a 2-year period in patients with DS at an outpatient clinic of a German epilepsy center. Data on the course of epilepsy, anticonvulsant treatment, and direct costs were recorded using the electronic seizure diary Epivista® and patients' files.We enrolled 13 patients with DS (6 females, mean age: 12.3 ± 7.5 years) between 2007 and 2010 and evaluated them during a 1-year baseline. All patients had drug-resistant epilepsy and their seizures failed to improve with a mean number of 6.7 ± 3.4 anticonvulsants. They had an overall mean seizure frequency of 102.1 seizures per year (median: 31, range: 3–538) with 43.2 GTCSs per year (median: 14, range: 0–228). We estimated the annual total direct costs at €6506 ± 3974 (range: €1174–11,783) per patient with hospitalization (68.9% of total direct costs) as the major cost factor ahead of costs for anticonvulsants (24.0%). For the 1-year follow-up period, less severely affected patients were continued on conventional anticonvulsants (n = 4) or switched to adjunctive treatment with stiripentol and clobazam (n = 9). In the latter group, six patients (67%) were long-term responders, with between 25% and 100% seizure reduction with respect to either GTCSs or the overall seizure frequency. This reduction in seizure frequency was associated with a shift in the distribution of cost components towards higher medication costs and decreased hospitalization costs. The total direct costs increased by 42.7%, mainly due to the newly introduced stiripentol, with an annual cost of €6610.This study showed that direct costs of patients with DS were above the average European costs of drug-resistant epilepsy in children. Treatment with new anticonvulsants resulted in reduction of seizures and inpatient admissions.     

Electroencephalographic features of benign adult familial myoclonic epilepsy

ObjectiveTo investigate electroencephalographic (EEG) features of benign adult familial myoclonic epilepsy (BAFME).MethodsWe reviewed interictal EEG features in patients with BAFME treated between April 2005 and November 2012 at a tertiary referral center. The diagnostic criteria for BAFME were the presence of infrequent generalized tonic–clonic seizures, myoclonus or myoclonic seizures, and autosomal dominant inheritance. Interictal EEG findings of epilepsy with generalized tonic–clonic seizure only (EGTCS) were reviewed for comparison. We randomly selected 10 generalized spike/polyspike and wave complexes (GSW) for each BAFME patient and measured the duration of them. Photic stimulation and hyperventilation were performed in all.ResultsNineteen (eight men, 11 women) patients with BAFME were included in this study. The mean frequency of GSW was 4.3 ± 1.0 Hz (mean ± SD, n = 14) in BAFME and 3.2 ± 0.8 Hz (n = 10) in EGTCS. There was a statistically significant difference (p = 0.008) between the two. Photoparoxysmal responses (PPR) were noted in 18 (95%) patients with BAFME but 1 (10%) with EGTCS.ConclusionFaster frequency of GSW, compared with that in EGTCS, accompanied by PPR may be characteristic EEG features of BAFME.SignificanceThese findings may lead the diagnosis of BAFME.     

First European long-term experience with the orphan drug rufinamide in childhood-onset refractory epilepsy

ObjectiveRecently, we published the first postmarketing European experience with rufinamide (RUF) in a retrospective 12-week observational study. This follow-up report summarizes the long-term effectiveness and tolerability of RUF after 18 months for the same patient sample.MethodsIn total, 52 of 60 initially included patients from eight centers in Germany and Austria (45 children and 15 adults aged 1–50 years) with various severe and inadequately controlled epilepsy syndromes continued treatment with RUF after the initial 3-month observation period (mean final dose: 38.2 ± 17.3 mg/kg/day). Efficacy was assessed by seizure frequency evaluated by comparison with baseline frequency. Tolerability was evaluated by analysis of parental report of adverse events and laboratory tests. Responders were defined as patients who achieved a 50% or greater decrease in countable seizures within 18 months of initiating RUF therapy.ResultsMean overall duration of RUF treatment was 14.5 months (range: 3–18 months). Retention rate, defined as the percentage of patients still taking RUF after 18 months, was 41.7% (n = 25/60). The overall response rate after 18 months was 26.7% (16/60 patients). The highest response rates were found in the subgroup of patients with Lennox–Gastaut syndrome (LGS, 35.5%) and in patients with other generalized epilepsy syndromes. Complete seizure control was maintained in one patient (1.6%). A total of 73 adverse events were reported in 37 of 60 patients. The most frequently occurring adverse events were fatigue (18.3%), vomiting (15.0%), and loss of appetite (10.0%). Only 4 new adverse events were reported after week 12. No serious adverse events were observed.ConclusionsThe present data suggest that RUF is efficacious and well tolerated in the long-term treatment of children and adults with various epilepsy syndromes and difficult-to-control seizures.