Specific adverse effects of antiepileptic drugs — A true-to-life monotherapy study

BackgroundIn patients taking antiepileptic drugs (AEDs) for epilepsy, adverse effects (AEs) often lead to unfavorable quality of life, impaired adherence, and, eventually, discontinuation of pharmacological treatment. In a true-to-life sample of subjects from our academic epilepsy outpatient clinic, we aimed to identify predictors for overall high AE burden and for specific AEs focusing on patients on monotherapy.MethodsAll patients ≥ 16 years of age with epilepsy for ≥ 12 months were routinely asked to complete the Liverpool Adverse Event Profile (LAEP) just before their appointment. Demographic, epilepsy, and treatment variables were derived from our comprehensive outpatient database.ResultsOut of 841 patients, 438 (61% female, mean age: 44.7 ± 17.1 years) on monotherapy were included in this study. Levetiracetam (n = 151), lamotrigine (n = 167), valproic acid (n = 73), or controlled-release carbamazepine (n = 47) were the most commonly used antiepileptic drugs (AEDs). Independent predictors for general high AE burden (LAEP score ≥ 45) were duration of epilepsy, lack of 12-month seizure freedom, and partial epilepsy, but none of the four individual AEDs. The most frequent LAEP-defined specific AEs were sleepiness, difficulty concentrating, tiredness, and memory problems. The three most frequent independent predictors for each of the 19 AEs were lack of 12-month seizure freedom (13/19 AEs), individual AED (7/19 AEs), and partial epilepsy (6/19 AEs). Levetiracetam was independently associated with anger/aggression, nervousness/agitation, upset stomach, depression, and sleep disturbance; lamotrigine with nervousness/agitation, upset stomach, and difficulty concentrating; and valproic acid with upset stomach and shaky hands.ConclusionIndividual AEDs independently predicted some specific AEs, but not overall high AE burden. Our findings may help to characterize patients with epilepsy who are at high risk for specific AEs. Dose reduction or change to another AED may reduce LAEP score and potential nonadherence.     

Antiepileptic drug prescribing patterns in Iraq and Afghanistan war veterans with epilepsy

ObjectiveWe examined patterns of antiepileptic drug (AED) use in a cohort of Iraq/Afghanistan war veterans (IAVs) who were previously identified as having epilepsy. We hypothesized that clinicians would be more likely to prescribe newer AEDs and would select specific AEDs to treat seizures based on patient characteristics including gender and comorbidities.MethodsFrom the cohort of IAVs previously identified with epilepsy between fiscal years 2009 and 2010, we selected those who received AEDs from the Veterans Health Administration in FY2010. Regimens were classified as monotherapy or polytherapy, and specific AED use was examine overall and by gender. Multivariable logistic regression examined associations of age; gender; race/ethnicity; medical, psychiatric, and neurological comorbidities; and receipt of neurology specialty care associated with the six most commonly used AEDs.ResultsAmong 256,284 IAVs, 2123 met inclusion criteria (mean age: 33 years; 89% men). Seventy-two percent (n = 1526) received monotherapy, most commonly valproate (N = 425) and levetiracetam (n = 347). Sixty-one percent of those on monotherapy received a newer AED (levetiracetam, topiramate, lamotrigine, zonisamide, oxcarbazepine). Although fewer women than men received valproate, nearly 90% (N = 45) were of reproductive age (≤ 45 years). Antiepileptic drug prescribing patterns were associated with posttraumatic stress disorder, bipolar disorder, cerebrovascular disease, dementia/cognitive impairment, headache, and receipt of neurological specialty care (all p < 0.01).SignificanceIn this cohort of veterans with epilepsy, most received AED monotherapy and newer AEDs. Prescribing patterns were different for men and women. The patterns observed between AEDs and neurological/psychiatric comorbidities suggest that clinicians are practicing rational prescribing.     

Efficacy,tolerability, and retention rates of zonisamide in older adult patients with focal-onset epilepsy: Experiences from two tertiary epilepsy centers

ObjectiveThe objective of this study was to evaluate the efficacy, tolerability, and retention rates for zonisamide (ZNS) in older adult patients with focal-onset epilepsy.Patients and methodsChart reviews of patients aged 60 years and older with focal-onset epilepsy treated with ZNS in two tertiary epilepsy centers were analyzed retrospectively.ResultsEighty-five patients (41 males, 44 females) aged over 60 years (range: 60–81) with focal-onset epilepsy treated with ZNS were identified; 55.3% of the patients (n = 47) were on monotherapy. The median and average doses of ZNS doses were 200 mg/day (range: 100–400) and 212.9 ± 84.2 mg/day, respectively. With ZNS treatment, 67.1% of the patients (n = 57) were seizure-free for a median of 28 months (range: 10–56) whereas 20% (n = 17) of the patients had seizures that were unresponsive to ZNS treatment. Best seizure control was achieved in patients with poststroke epilepsy; seizure freedom was 80% in this subgroup.Overall retention rate was found to be 83.5%. There was no significant relation between receiving poly- or monotherapy and discontinuation of ZNS (p = 0.18).Thirty-two of the patients (37.6%) lost weight. Median weight loss was 8 kg (range: 2–16). There was no significant correlation between weight loss and the administered doses of ZNS (r = 0.34; p = 0.12).ConclusionDespite limitations due to the retrospective design of the study, the results show that ZNS is a well-retained drug with high efficacy in older adult patients with epilepsy.     

Population-based study of antiepileptic drug exposure in utero—Influence on head circumference in newborns

PurposeTo study the effect of AED exposure on head circumference in the newborn.MethodsData on all Swedish singletons births between 1995 and 2005, over 900,000 births, were obtained from the Swedish Medical Birth Registry. The effects of AEDs on birth-weight-adjusted mean head circumference (bw-adj-HC) were estimated by comparison with data from all births in an analysis which was adjusted for year of birth, maternal age, parity, maternal smoking, and maternal body mass index.ResultsA significant reduction of mean bw-adj-HC was seen after both carbamazepine (CBZ) (standard deviation scores (SDS) = 0.15, p < 0.001) and valproic acid (VPA) (SDS = 0.10, p = 0.04) in monotherapy. No effect on mean bw-adj-HC was seen for phenytoin, clonazepam, lamotrigine and gabapentin. There was a significant increase in the occurrence of microcephaly (bw-adj-HC smaller than 2 SD below the mean) after any AED polytherapy (OR = 2.85, 95% CI: 1.74–4.78) but not after AED monotherapy or monotherapy with CBZ or VPA. CBZ or VPA was taken by 71% of the pregnant mothers on AED, and the usage increased over time.ConclusionsCBZ and VPA in monotherapy during pregnancy reduce mean bw-adj-HC. AED polytherapy increases the rate of microcephaly but no significant effect is seen of AED monotherapy. The possible significance for the further development of the child is uncertain but should be explored.     

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”.     

Health-care costs and utilization related to long- or short-acting antiepileptic monotherapy use

PurposeThis study aimed to compare health-care utilization and costs in patients treated with long-acting (LA) vs. short-acting (SA) antiepileptic drug (AED) monotherapy.MethodsWe conducted a cross-sectional study of claims from the OptumInsight™ database. Our analysis was restricted to adults diagnosed with epilepsy and who used AED monotherapy. Patients were excluded if they used > 1 type of AED, had < 9 months of treatment, or had a treatment gap of > 60 days. Antiepileptic drugs were classified as LA or SA based on published data and expert opinion. Medical and pharmacy claims were used to estimate health-care utilization and costs, and baseline group differences were adjusted using multivariate analyses.ResultsThere were 4058 (49.6%) LA AED users and 4122 (50.4%) SA AED users. Medication possession ratios (MPRs) were not significantly different between LA AED users and SA AED users (P = 0.125). Long-acting AED users had lower mean overall health-care costs ($9757 vs. $12,689), lower epilepsy-related costs ($3539 vs. $5279), and lower rate of overall (8.8% vs. 10.9%) and epilepsy-related hospitalizations (5.7% vs. 7.6%) compared with SA AED users (all P < 0.01). After adjusting for demographics and clinical characteristics, mean overall costs were lower by $686 and the mean epilepsy-related costs were lower by $894 in LA AED users.ConclusionAlthough MPRs were similar in LA AED and SA AED groups, patients treated with LA monotherapy had a lower economic burden compared with those treated with SA monotherapy, indicating that using AEDs with extended duration of action is associated with decreased health-care use and lower health-care costs.     

Seizure outcome after AED failure in pediatric focal epilepsy: Impact of underlying etiology

ObjectiveThis study aimed to identify long-term seizure outcome in pediatric nonsyndromic focal epilepsy after failure of serial antiepileptic drugs (AEDs) due to lack of efficacy.MethodsChildren (1 month–17 years) with new-onset focal epilepsy not meeting the criteria for a defined electroclinical syndrome diagnosed between 1980 and 2009 while residing in Olmsted County, MN, were retrospectively identified. Medical records of those followed for ≥ 2 years were reviewed to assess etiology, the number of AEDs that failed due to lack of efficacy, and seizure outcome at final follow-up. Etiology was classified into structural/metabolic, genetic, or unknown. Favorable outcome was defined as seizure freedom ≥ 1 year, on or off AEDs, without prior epilepsy surgery. Poor outcome was defined as ongoing seizures in the preceding year or having undergone prior epilepsy surgery.ResultsNonsyndromic focal epilepsy accounted for 275/468 (59%) of all patients with newly diagnosed epilepsy — of these, 256 (93%) were followed for a minimum of two years and were included in the study. Median duration of follow-up was 10.0 years. At least one AED had failed due to lack of efficacy in 100 (39.1%) children. Favorable outcomes occurred in 149/156 (95.5%) children with no AED failure, 16/30 (53.3%) with one AED failure, 8/25 (32%) with two AED failures, and only 2/45 (4.4%) with three AED failures. After two AED failures, the seizures of nearly one-quarter of children who had epilepsy with an unknown cause responded favorably to the third AED compared with only 7.8% of the cohort that had epilepsy with a structural/metabolic cause. Children with a remote brain insult had a significantly higher likelihood of favorable outcome with serial AEDs than those with other structural abnormalities.SignificanceEtiology is an important determinant of pharmacoresistance in nonsyndromic focal epilepsy. Surgical evaluation should be considered after failure of 1–2 AEDs in those who have epilepsy with structural causes, excluding remote brain insults. Conversely, as surgical success is lower with normal MRI or more diffuse brain insults, it appears reasonable to hold off surgical evaluation until 2–3 AEDs have failed in such children.     

Quality of life and treatment satisfaction in Spanish epilepsy patients on monotherapy with lamotrigine or valproic acid

BackgroundPatients suffering from epilepsy have an impaired health related quality of life (HRQoL) because of seizures and treatment adverse events. Epilepsy affects differently both genders, due to hormonal influence in women. The aim of this study is to assess the impact on HRQoL and treatment satisfaction in epilepsy patients treated with stable doses of lamotrigine and valproic acid.MethodsObservational cohort prospective study was conducted in 18 Spanish neurology sites. Patients with clinically stable partial or generalized epilepsy, already receiving lamotrigine or valproic acid on monotherapy, were assessed in two visits: baseline and at 6 months. Socio-demographic and clinical variables were recorded at baseline; HRQoL (QOLIE-10) treatment satisfaction and women image self-perception were assessed at both visits. Impact on HRQoL was assessed in both treatment arms overall and in the women subgroup.ResultsA total of 107 patients were evaluated; 53 (14 men, 39 women) on lamotrigine and 54 (27 men, 27 women) on valproic acid. Mean (SD) age was 30.4 (9.1) years and mean (SD) time since epilepsy diagnosis was 8 (8.1) years. Mean (SD) QOLIE-10 score at baseline was 73.9 (15.7) points (76.6 and 71.4 for lamotrigine and valproic, respectively). At follow up, patients reported better HRQoL on both lamotrigine (78.8 points) (p < 0.05) and on valproic (72.4 points) in comparison with baseline. Women's HRQoL at follow up was better on the lamotrigine arm compared with valproic acid: 78.8 (12.8) vs. 70.3 (15.9) (p < 0.05). Women on the lamotrigine arm declared higher satisfaction with treatment and higher disagreement with the different statements referred to a negative image self-perception.ConclusionsChronic patients with epilepsy already treated with lamotrigine slightly improved HRQoL at 6 month follow up, whereas no significant changes were observed in the valproic acid group. Lamotrigine impact on patients’ HRQoL seems to be even more positive in the subgroup of women.     

Lacosamide in patients with temporal lobe epilepsy: An observational multicentric open-label study

PurposeThe aim of this study was to evaluate the efficacy and tolerability of lacosamide (LCM) both as add-on therapy and monotherapy in patients with temporal lobe epilepsy (TLE) based on an observational, prospective, multicenter study.MethodsWe enrolled 100 patients (mean age: 43.4 ± 12.53 years, 57 females) with nonlesional TLE and TLE with hippocampal sclerosis (HS) that did not respond to the first drug and who were referred to epilepsy centers of the University of Catanzaro, University of Palermo, IRCSS Neuromed of Pozzilli, and Otto-von-Guericke University of Magdeburg. In this open-label, multicenter trial, patients were initiated on oral LCM as add-on therapy to first AED monotherapy or as a later add-on to two concomitant AEDs. Seizure frequency changes and adverse events were recorded for at least six months after LCM was added.ResultsFourteen patients dropped out because of positive MRI findings other than HS. Patients received LCM at 200–400 mg/day. Fifty-eight out of these 86 patients with seizures that were previously drug-resistant had reduced seizure frequency after introduction of LCM. Forty-five out of 86 patients were classified as responders (12 were seizure-free, 33 achieved a reduction > 50%). Interestingly, five patients out of 86 achieved seizure freedom for at least one year and progressively switched to monotherapy with LCM, and all five remained seizure-free at follow-up (6–48 months).ConclusionsOur results may suggest that LCM at doses of 200 to 400 mg/day reduces seizure frequency in adults with TLE regardless of the presence of HS, and that it may be considered as a first add-on treatment for patients with pharmacoresistant TLE.     

Clinical and economic burden of breakthrough seizures

PurposeThe purpose of this study was to measure health-care resource utilization and costs in treatment-adherent, previously seizure-free patients with epilepsy who were treated in the inpatient/emergency room (ER) setting for new-onset seizures, compared with matched controls.MethodsThe study used a retrospective case/control study design using administrative claims from the IMS PharMetrics™ database. We identified adult patients with epilepsy with 1 + ER visit/hospitalization with primary diagnosis of epilepsy between 1/1/2006 and 3/31/2011, preceded by 6 months of seizure-free activity and antiepileptic drug (AED) treatment adherence (≥ 80% of days covered by any AED); the first observed seizure defined the “breakthrough” seizure/index event. Treatment-adherent patients with epilepsy without any ER/hospital admission for seizures served as controls: an outpatient epilepsy-related medical claim within the selection window was chosen at random as the index date. The following were continuous enrollment requirements for all patients: ≥ 12-month pre- and ≥ 6-month postindex. Each case matched 1:1 to a control using propensity score matching. All-cause and epilepsy-related (epilepsy/convulsion diagnosis, AED pharmacy) resource utilization and unadjusted and adjusted direct health-care costs (per person, 2012 US dollars (USD)) were assessed in a 6-month follow-up period.Principal resultsThere were 5729 cases and 14,437 controls eligible. The final sample comprised 5279 matched case/control pairs. In unadjusted analyses, matched cases had significantly higher rates of all-cause hospitalization and ER visits compared to controls and significantly higher total all-cause direct health-care costs (median $12,714 vs. $5095, p < 0.001) and total epilepsy-related costs among cases vs. controls (median $7293 vs. $1712, p < 0.001), driven by higher inpatient costs. Among cases, costs increased with each subsequent seizure (driven by inpatient costs). Cases had 2.3 times higher adjusted all-cause costs and 8.1 times higher adjusted epilepsy-related costs than controls (both p < 0.001).ConclusionInpatient/ER-treated breakthrough seizures occurred among 28.4% of our treatment-adherent study sample and were associated with significant incremental health-care utilization and costs, primarily driven by hospitalizations. Our findings suggest the need for better seizure control via optimal patient management and the use of effective AED therapy, which can potentially lower health-care costs.     

Epidemiology of uncontrolled epilepsy in the Al-Kharga District,New Valley,Egypt

BackgroundDespite advances in treating epilepsy, uncontrolled epilepsy continues to be a major clinical problem. Therefore, this work aimed to study the epidemiology of uncontrolled epilepsy in Al-Kharga District, New Valley.MethodsThis study was carried out in 3 stages via door-to-door screening of the total population (62,583 persons). All suspected cases of epilepsy were subjected to case ascertainment, conventional ElectroEncephaloGraphy (EEG), and the Stanford-Binet Intelligence Scale. Patients who had been receiving suitable anti-epileptic drugs (AEDs) over the previous 6 months and were having active seizures were considered uncontrolled, according to Ohtsuka et al.²³ The patients underwent serum AED level estimation, video EEG monitoring, and brain MRIs. Fifty age- and gender-matched patients with controlled epilepsy were chosen for statistical analysis and compared with true intractable patients.ResultsA total of 437 patients with epilepsy were identified, 30.7% of whom (n = 134/437) were uncontrolled, with a prevalence of 2.1/1000. A total of 52.2% of uncontrolled patients (n = 70/134) were inappropriately treated, while 47.8% (n = 64/134) were compliant with appropriate treatments. Video monitoring EEG of compliant uncontrolled patients demonstrated that 78.1% patients (n = 50/64) had definite epilepsy, while 21.9% (n = 14/64) had psychogenic non-epileptic seizures (PNES). A logistic regression analysis revealed that status epilepticus, focal seizures, and mixed seizure types were risk factors for intractability.     

Healthcare utilization and costs in children with stable and uncontrolled epilepsy

ObjectiveEpilepsy adversely affects childhood development, possibly leading to increased economic burden in pediatric populations. We compared annual healthcare utilization and costs between children (< 12 years old) with stable and uncontrolled epilepsy treated with antiepileptic drugs (AEDs).MethodsChildren (< 12 years old) with epilepsy (ICD-9-CM 345.xx or 780.39) in 2008 were identified in the MarketScan claims database from 2007 to 2009. Patients with “stable” epilepsy used the same AED for ≥ 12 months, and patients with “uncontrolled” epilepsy were prescribed additional AED(s) during that period. For patients with uncontrolled epilepsy, the study index date was the start of additional AED(s); for patients with stable epilepsy, the study index date was a random AED fill date. Epilepsy-related utilization included medical services with 345.xx or 780.39 in any diagnosis field and AED fills. Epilepsy-related costs included AEDs, medical claims with epilepsy in any diagnosis field, and certain tests. We adjusted for baseline cohort differences (demographics, region, usual-care physician specialty, and comorbidities) using logistic regression and analysis of covariance.ResultsTwo thousand one hundred seventy patients were identified (mean: 7.5 years; 45.3% were female; Charlson comorbidity index: 0.3; 422 (19.4%) patients with uncontrolled epilepsy). Patients with uncontrolled epilepsy faced more hospitalizations (30.1% vs. 12.0%) and greater overall ($30,343 vs. $18,206) and epilepsy-related costs ($16,894 vs. $7979) (all p < .001). Adjusting for baseline measures, patients with uncontrolled epilepsy had greater odds of hospitalization (OR: 2.5; 95% CI: 1.9–3.3) and costs (overall: $3908, p = .087; epilepsy-related: $5744, p < .001).ConclusionsChildren with uncontrolled epilepsy use significantly more healthcare resources and have a greater economic burden than children with stable epilepsy. However, epilepsy accounted for only half of overall costs, indicating that comorbid conditions may add substantially to the disease burden.     

Fatigue during treatment with antiepileptic drugs: A levetiracetam-specific adverse event?

PurposeTo examine the prevalence and clinical correlates of fatigue as an adverse event (AE) of antiepileptic drug (AED) treatment in patients with epilepsy.MethodsData from 443 adult outpatients with epilepsy assessed with the Adverse Event Profile (AEP) and the Neurological Disorder Depression Inventory for Epilepsy (NDDIE) were analysed.ResultsFatigue is reported by 36.6% of patients as always a problem during AED treatment. Fatigue is more likely to be reported by females (64.8% vs. 35.2%; Chi-Square = 16.762; df = 3; p = 0.001) and during treatment with levetiracetam (42.3% vs. 33.2%; Chi-Square = 11.462; df = 3; p = 0.009). The associations with the female gender and levetiracetam treatment were not mediated by depression, as identified with the NDDIE, and could not be simply explained by the large number of subjects on levetiracetam treatment, as analogous figures resulted from the analysis of a monotherapy subsample (41.7% vs. 30.3%; Chi-Square = 11.547; df = 3; p = 0.009).ConclusionsOne third of patients with epilepsy reports fatigue as a significant problem during AED treatment. Fatigue is more likely to be reported by females and seems to be specifically associated with LEV treatment. However, fatigue is not mediated by a negative effect of LEV on mood.     

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.     

Clinical characteristics and treatment responses in new-onset epilepsy in the elderly

PurposeEpidemiologic studies have shown that the incidence of epilepsy is the highest in the elderly population. Because the elderly constitutes the most rapidly growing population, epilepsy in this group is an important health issue worldwide. To identify the characteristics of epilepsy in the elderly, we reviewed our experience at a tertiary referral center in Japan.MethodsWe searched all electronic medical records of the past 6 years at the epilepsy clinic of the hospital affiliated to our University-affiliated hospital. We defined an elderly person as an individual aged 65 years and above. All patients underwent history and physical examinations, 3 T magnetic resonance imaging and/or computer tomography, and electroencephalogram (EEG). The diagnosis of epilepsy, age of onset, etiology, and antiepileptic medication were recorded.ResultsWe identified 70 patients who developed epilepsy after the age of 65 years. The mean age of seizure onset was 73.1 years and 52.9% patients were males. Complex partial seizures (CPS) without secondarily generalization (n = 33, 47.1%) were most frequent. The most frequent diagnosis was temporal lobe epilepsy (n = 50, 71.4%). Etiological diagnosis was possible in nearly 50% patients, including those with cerebrovascular disease. A clear cause of epilepsy was not found (i.e., non-lesional epilepsy) in 52.8% patients. Interictal EEG revealed focal epileptiform discharges in 72.9% (n = 51) patients. Of the 54 patients who were followed more than 1 year, 42 patients (77.8%) were on antiepileptic monotherapy and 52 patients (96.3%) had been seizure-free for more than 1 year.ConclusionThe most frequent diagnosis in our cohort of elderly persons with new-onset epilepsy was temporal lobe epilepsy. Non-lesional temporal lobe epilepsy was not uncommon. Epileptogenecity was relatively low in elderly patients and they responded well to antiepileptic medication.     

Prospective study on the withdrawal and reinstitution of antiepileptic drugs among seizure-free patients in west China

This study explored the relapse rates and risk factors for seizure recurrence after discontinuing antiepileptic drug (AED) therapy among seizure-free patients in west China, and explored whether to reinstitute AED immediately after a single seizure after AED withdrawal. Patients with epilepsy who were seizure-free for at least 2 years and decided to gradually stop AED therapy were followed up every 3 months for seizure relapse. Patients who experienced their first seizure after drug withdrawal were divided into two groups according to their willingness to reinstitute AED therapy, and were followed up until their second seizure. In the mean 29.35 months of follow-up, 37 patients (37/162, 22.8%) suffered at least one seizure after withdrawal. The cumulative probability of seizure recurrence was 16% at 12 months and 20.2% at 24 months. AED response time >1 year and multiple types of seizure were identified as risk factors for seizure recurrence. Eight patients (8/32, 25%) suffered a second seizure within 1 year after the first whether or not they reinstituted AED immediately. There were no significant demographic or clinical differences between patients who reinstituted AED therapy and those who did not. The epilepsy recurrence rate after AED withdrawal is relatively low, with a relatively slow tapering process. Patients with long AED response times and/or multiple types of seizures have a higher risk of seizure recurrence. The first seizure after drug withdrawal is not an indication for immediate AED reinstitution, but may be recommended after a second seizure.     

Self reported adverse effects of mono and polytherapy for epilepsy

PurposeAdverse effects of anti epileptic drugs (AEDs) can significantly affect the life of people with epilepsy. We used a register to determine if polytherapy with AED has more adverse effects than monotherapy.MethodsWe established a register for people with epilepsy (www.UKAED.info). Participants were requested to complete the Liverpool Adverse Event Profile (LAEP) to quantify adverse effects. We also recorded type of epilepsy, seizure control and AED including drug doses. Five hundred and seventy six complete data sets were available, monotherapy (n = 186), polytherapy (n = 325) and control subjects not taking AED (n = 65).ResultsThe mean LAEP scores in polytherapy (45.56, confidence interval (CI) = 44.36–46.76) were significantly higher than the mean LAEP scores in monotherapy (42.29, CI = 40.65–44.02) and the mean LAEP scores in controls (33.25, CI = 31.05–35.44). Tiredness, memory problems and difficulty concentrating were the most common symptoms in patients taking AED and were consistently higher in polytherapy than in monotherapy. Tiredness was reported as always or sometimes being a problem in (polytherapy/monotherapy/controls) 82.5%/75.6%/64.6%, memory problems in 76%/63.2%/29.2% and difficulty concentrating in 68%/63.9%/30.8%. The proportion of seizure-free patients was significantly lower in the polytherapy group (17%) than in the monotherapy group (55%). Depression rates between the monotherapy and polytherapy groups were similar. Drug dosages were higher in polytherapy, however this did not reach statistical significance.ConclusionPatients on polytherapy had significantly higher LAEP scores than patients on monotherapy. This should be carefully discussed with the patient before a second AED is added.     

Impact of planning of pregnancy in women with epilepsy on seizure control during pregnancy and on maternal and neonatal outcomes

PurposeTo investigate whether planning of pregnancy in women with epilepsy affects seizure control during pregnancy and to compare the maternal and neonatal outcomes in planned and unplanned pregnancies.MethodsThis was a retrospective cohort study of 153 pregnant women with epilepsy who were treated at the University of Tsukuba Hospital and Hokkaido University Hospital between 2003 and 2011. Twenty-one pregnancies were excluded due to insufficient data. Data of patients followed by neurologists during their planned pregnancies (planned-pregnancy group, n = 51) were compared to those of patients referred to neurologists after conception for managing epilepsy during pregnancy (unplanned-pregnancy group, n = 81). The treatment profile for epilepsy, seizure control, and maternal and neonatal outcomes in both groups were compared using Chi-square test or Fisher's exact test and Mann–Whitney U test.ResultsCompared to the unplanned-pregnancy group, the planned-pregnancy group showed a significantly greater proportion of patients receiving monotherapy with antiepileptic drugs (80% vs. 61%: planned vs. unplanned, P = 0.049) and those not requiring valproic acid (77% vs. 56%, P = 0.031). Furthermore, the frequency of epileptic seizures (16% vs. 35%, P = 0.018) and changes in antiepileptic drugs (24% vs. 41%, P = 0.042) were significantly lower in the planned-pregnancy group than in the unplanned-pregnancy group. No significant intergroup differences were noted in the obstetric complications and neonatal outcomes, including congenital malformations.ConclusionFor women with epilepsy, planning of pregnancy is associated with good seizure control during pregnancy and less fetal exposure to antiepileptic drugs.     

What do epileptologists recommend about discontinuing antiepileptic drugs for a second time in children?

ObjectiveThere is a broad consensus that antiepileptic drugs (AEDs) may be withdrawn after two years of seizure freedom for most children with epilepsy. If seizures recur and are, again, completely controlled with AEDs, little is known about discontinuing a second time. We surveyed American and Canadian pediatric epileptologists to understand their current practice.MethodsIn 2014, a survey was sent via e-mail to 193 pediatric epileptologists to learn about AED discontinuation practices in children. The survey asked direct questions about practice and posed five “real-life” cases where the decision to discontinue might be difficult. Participants were identified through membership lists of several US and Canadian epilepsy organizations.ResultsThere were 94 (49%) completed surveys. Sixty-three participants had ≥ 10 years in practice (“more experienced”: mean 23 ± 9 years), and 31 had < 10 years (“less experienced”: mean 6 ± 2). Overall, 62% recommended AED discontinuation for the first time after 2–3 years of seizure freedom, and 61% recommended discontinuation for the second time after 2–3 years. Fifty-six percent of “more experienced” clinicians required a longer seizure-free period prior to a second discontinuation (p < 0.001) compared with 26% of “less experienced” clinicians (p = ns). Overall, most participants suggested an AED taper duration of 2–6 months for the first and second attempts, 52% and 68%, respectively. Both groups wean AEDs more slowly during the second attempt (p < 0.001). There was only 40–60% agreement among participants to discontinue AEDs in four of the cases.ConclusionNearly half (46%) of pediatric epileptologists require a longer seizure-free period the second time they attempt to discontinue AEDs compared with the first attempt and wean down AEDs somewhat more slowly. Although a variety of factors influence decision-making, there was a high level of disagreement to discontinue AEDs a second time in “real-life” cases.