Lacosamide and pregnancy: Data from spontaneous and solicited reports.

OBJECTIVE: In pregnancy, it is important to balance the risks of uncontrolled epileptic seizures to the mother and fetus against the potential teratogenic effects of antiseizure medications. Data are limited on pregnancy outcomes among patients taking lacosamide (LCM), particularly when taken as monotherapy. The objective of this analysis was to evaluate the pregnancy outcomes of LCM-exposed pregnancies. METHODS: This analysis included all reports in the UCB Pharma pharmacovigilance database of exposure to LCM during pregnancy from spontaneous sources (routine clinical settings) or solicited reports from interventional clinical studies and noninterventional postmarketing studies. Prospective and retrospective reports were analyzed separately. RESULTS: At the data cutoff (August 31, 2021), there were 202 prospective pregnancy cases with maternal exposure to LCM and known outcomes. Among these cases, 44 (21.8%) patients received LCM monotherapy and 158 (78.2%) received LCM polytherapy. Most patients received LCM during the first trimester (LCM monotherapy: 39 [88.6%]; LCM polytherapy: 143 [90.5%]). From the prospective pregnancy cases with maternal LCM exposure, there were 204 reported outcomes (two twin pregnancies occurred in the polytherapy group). The proportion of live births was 84.1% (37/44) in patients who received LCM as monotherapy, and 76.3% (122/160) for LCM polytherapy. The overall proportion of abortions (for any reason) was 15.9% (7/44) with LCM monotherapy, and 22.5% (36/160) with LCM polytherapy. Congenital malformations were reported in 2.3% (1/44) of known pregnancy outcomes with maternal exposure to LCM monotherapy, and 6.9% (11/160) with polytherapy. SIGNIFICANCE: Our preliminary data do not raise major concerns on the use of LCM during pregnancy. Most pregnancies with LCM exposure resulted in healthy live births, and no new safety issues were identified. These findings should be interpreted with caution, as additional data are needed to fully evaluate the safety profile of LCM in pregnancy.

Mood disorders in adults with epilepsy: a review of unrecognized facts and common misconceptions.

Epilepsy is one of the most common neurologic conditions. Its clinical manifestations are not restricted to seizures but often include cognitive disturbances and psychiatric disorders. Prospective population-based studies have shown that people with epilepsy have an increased risk of developing mood disorders, and people with a primary mood disorder have an increased risk of developing epilepsy. The existence of common pathogenic mechanisms in epilepsy and mood disorders may explain the bidirectional relation between these two conditions. Recognition of a personal and family psychiatric history at the time of evaluation of people for a seizure disorder is critical in the selection of antiseizure medications: those with mood-stabilizing properties (e.g., lamotrigine, oxcarbazepine) should be favoured as a first option in those with a positive history while those with negative psychotropic properties (e.g., levetiracetam, topiramate) avoided. While mood disorders may be clinically identical in people with epilepsy, they often present with atypical manifestations that do not meet ICD or DSM diagnostic criteria. Failure to treat mood disorders in epilepsy may have a negative impact, increasing suicide risk and iatrogenic effects of antiseizure medications and worsening quality of life. Treating mood disorders in epilepsy is identical to those with primary mood disorders. Yet, there is a common misconception that antidepressants have proconvulsant properties. Most antidepressants are safe when prescribed at therapeutic doses. The incidence of seizures is lower in people randomized to antidepressants than placebo in multicenter randomized placebo-controlled trials of people treated for a primary mood disorder. Thus, there is no excuse not to prescribe antidepressant medications to people with epilepsy.

[Epilepsy and pregnancy]. / Epilepsie und Schwangerschaft.

BACKGROUND: Regarding treatment of women of childbearing potential with epilepsy, several aspects of family planning and desire to have children have to be taken into account. OBJECTIVE: Overview of current data on mutual implications of epileptic seizures, antiseizure medication (ASM), pregnancy and child development. METHOD: Review of the current literature, discussion and presentation of resulting treatment recommendations. RESULTS: Many ASMs bear the potential for clinically relevant interactions with both contraceptives and altered concentrations of sexual hormones and modified pharmacokinetics during pregnancy. All ASMs show an increased risk for congenital malformations; however, due to seizure-related risks for the mother and child effective ASM treatment during pregnancy is crucial. CONCLUSION: When considering the special aspects of consultation and treatment of women of childbearing potential with epilepsy most pregnancies are uncomplicated.

The burden of chronic drug-refractory focal onset epilepsy: Can it be prevented?

Despite the many therapeutic options for epilepsy available today, a third of patients still have poorly controlled epilepsy. Over the years, their transition through lines of treatment exposes them to increased risk of disease progression, mortality, morbidity, mental distress, and not least significantly impaired quality of life (QoL). The present review explores the multiple factors contributing to the impairment of health-related QoL in PWE-including both seizure-related and non seizure-related. The analysis aims to identify potential areas of intervention and strategies for a more holistic approach to epilepsy care and inform policy-makers and healthcare providers in their approach to this condition.

Successful treatment of adult Dravet syndrome patients with cenobamate.

Dravet syndrome (DS) is a rare, drug-resistant, severe developmental and epileptic encephalopathy caused by pathogenic variants in the α subunit of the voltage-gated sodium channel gene SCN1A. Hyperexcitability in DS results from loss of function in inhibitory interneurons. Thus sodium channel blockers are usually contraindicated in patients with DS as they may lead to disease aggravation. Cenobamate (CNB) is a novel antiseizure medication (ASM) with promising rates of seizure freedom in patients with focal-onset, drug-resistant epilepsy. CNB blocks persistent sodium currents by promoting the inactive states of sodium channels. In a multi-center study, we analyzed retrospectively the effect of an add-on therapy of CNB in adult patients with DS. We report four adult patients with DS in whom the use of CNB resulted in a significant seizure reduction of more than 80%, with a follow-up of up to 542 days. CNB was the first drug in these patients that resulted in a long-lasting and significant seizure reduction. No severe adverse events occurred. We highlight CNB as an ASM that may lead to a clinically meaningful reduction of seizure frequency in adult patients with DS. It is unclear, however, if all patients with DS benefit, requiring further investigation and functional experiments.

Association between antiseizure medication use and risk of urinary tract infection: A case-control study.

AIM: The aim of this study was to analyze the association between antiseizure medication (ASM) and the risk of urinary tract infections (UTI) in patients with epilepsy treated in general practices in Germany. METHODS: This study includes a total of 2201 patients (mean age: 61.4) whose first documented UTI diagnosis occurred between January 2015 and December 2019 (index date) and who were prescribed at least one ASM in 1198 general practices in Germany within one year prior to the index date. Based on a case-control design, the association between predefined criteria and UTI was investigated by matching (1:1) controls without UTI to cases with UTI by sex, age, and codiagnoses. Logistic regression models were used to analyze the association between ASM use and UTI risk. RESULTS: In the first regression model, phenytoin (PHT), primidone, carbamazepine (CBZ), and valproate (VPA) were associated with an increased risk of UTI. In the second model, these associations were confirmed with effects per prescription for PHT, primidone, CBZ, and VPA use. Additionally, the effect per prescription was significant for oxcarbazepine (OXC), topiramate, and gabapentin. CONCLUSION: The study found that PHT, primidone, CBZ, and VPA in particular are associated with an increased risk of infections of the urinary tract. Oxcarbazepine, topiramate, and gabapentin are also associated with increased risk of UTI, albeit to a less significant extent. In general, the immunological and hematological side effects of these molecules may play an important role in the development of UTI under anticonvulsant therapy.

Oral anticoagulation in patients with atrial fibrillation and acute ischaemic stroke: design and baseline data of the prospective multicentre Berlin Atrial Fibrillation Registry.

AIMS: The Berlin Atrial Fibrillation Registry was designed to analyse oral anticoagulation (OAC) prescription in patients with atrial fibrillation (AF) and acute ischaemic stroke. METHODS AND RESULTS: This investigator-initiated prospective multicentre registry enrolled patients at all 16 stroke units located in Berlin, Germany. The ongoing telephone follow-up is conducted centrally and will cover 5 years per patient. Within 2014 and 2016, 1080 patients gave written informed consent and 1048 patients were available for analysis. Median age was 77 years [interquartile range (IQR) 72-83], 503 (48%) patients were female, and 254 (24%) had a transient ischaemic attack (TIA). Overall, 470 (62%) out of 757 patients with known AF and a (pre-stroke) CHA2DS2-VASc ≥ 1 were anticoagulated at the time of stroke. At hospital discharge, 847 (81.3%) of 1042 patients were anticoagulated. Thereof 710 (68.1%) received a non-vitamin K-dependent oral anticoagulant (NOAC) and 137 (13.1%) a vitamin K antagonist (VKA). Pre-stroke intake of a NOAC [odds ratio (OR) 15.6 (95% confidence interval, 95% CI 1.97-122)] or VKA [OR 0.04 (95% CI 0.02-0.09)], an index TIA [OR 0.56 (95% CI 0.34-0.94)] rather than stroke, heart failure [OR 0.49 (95% CI 0.26-0.93)], and endovascular thrombectomy at hospital admission [OR 12.9 (95% CI 1.59-104)] were associated with NOAC prescription at discharge. Patients' age or AF type had no impact on OAC or NOAC use, respectively. CONCLUSION: About 60% of all registry patients with known AF received OAC at the time of stroke or TIA. At hospital discharge, more than 80% of AF patients were anticoagulated and about 80% of those were prescribed a NOAC.

Trends in valproate use in patients in Germany between 2009 and 2017.

OBJECTIVE: The goal of this study was to analyze trends in valproate use in patients followed by neurologists and general practitioners in Germany between 2009 and 2017. METHODS: This study included all patients aged ≥15 years followed in 2009, 2013, and 2017 in neurological (N = 99) and general (N = 499) practices in Germany. Trends in valproate use were estimated based on the mean number of patients per practice who were prescribed valproate and the proportion of physicians prescribing it. Covariables included gender, age, and physician. This cross-sectional study uses descriptive statistics only. RESULTS: In total, 1,298,446 patients were followed in general and neurological practices in 2009, 1,358,160 in 2013, and 1,413,286 in 2017. The mean number of patients aged 15-45 years per practice with at least one valproate prescription decreased in neurological (men: 11.07 versus 9.92; women: 9.27 versus 5.88) and general practices (men: 0.82 versus 0.75; women: 0.60 versus 0.37) between 2009 and 2017. Moreover, the proportion of neurologists prescribing valproate in women between 15 and 45 years of age decreased over time (94% in 2009 versus 86% in 2017), and there was also a substantial decrease in the share of general practitioners prescribing valproate in men (47% versus 41%) and women between 15 and 45 years of age (37% versus 22%). CONCLUSION: The proportion of men and women between 15 and 45 years of age receiving valproate decreased in neurological and general practices in Germany between 2009 and 2017.

Incidence of epilepsy and associated factors in elderly patients in Germany.

AIMS: Little is known about the recent epidemiology of epilepsy in the elderly in Germany. Therefore, the goal of this study was to analyze the incidence of epilepsy and associated factors in elderly patients followed in general practices in this country. METHODS: The incidence of epilepsy was estimated using data from all patients aged ≥60 years who were followed in 1203 general practices in Germany in 2017 (IQVIA Disease Analyzer database). The association between predefined variables and epilepsy was further studied using a case-control design (n = 4690 matched pairs). Cases were patients aged ≥60 years who had received a first diagnosis of epilepsy in general practices between 2015 and 2017 (index date). Controls without epilepsy were matched (1:1) to cases by age, gender, index year, and physician. RESULTS: The incidence of epilepsy was 157 per 100,000 elderly persons. This incidence increased with age (92 per 100,000 persons in patients aged 60-65 years versus 311 in those aged >90 years) and was higher in men (166) than in women (150). The three disorders that had the strongest association with epilepsy were subarachnoid, intracerebral or intracranial hemorrhage (odds ratio [OR] = 3.31), stroke, including transient ischemic attack (OR = 2.32), and mental and behavioral disorders due to use of alcohol (OR = 2.20). In addition, there was a positive association between atypical neuroleptics and epilepsy (OR = 2.40). CONCLUSIONS: The incidence of epilepsy was high and increased with age in elderly patients followed in general practices in Germany. Addressing identified risk factors may help reduce the risk of developing epilepsy.

Burden analysis of rare microdeletions suggests a strong impact of neurodevelopmental genes in genetic generalised epilepsies.

Genetic generalised epilepsy (GGE) is the most common form of genetic epilepsy, accounting for 20% of all epilepsies. Genomic copy number variations (CNVs) constitute important genetic risk factors of common GGE syndromes. In our present genome-wide burden analysis, large (≥ 400 kb) and rare (< 1%) autosomal microdeletions with high calling confidence (≥ 200 markers) were assessed by the Affymetrix SNP 6.0 array in European case-control cohorts of 1,366 GGE patients and 5,234 ancestry-matched controls. We aimed to: 1) assess the microdeletion burden in common GGE syndromes, 2) estimate the relative contribution of recurrent microdeletions at genomic rearrangement hotspots and non-recurrent microdeletions, and 3) identify potential candidate genes for GGE. We found a significant excess of microdeletions in 7.3% of GGE patients compared to 4.0% in controls (P = 1.8 x 10-7; OR = 1.9). Recurrent microdeletions at seven known genomic hotspots accounted for 36.9% of all microdeletions identified in the GGE cohort and showed a 7.5-fold increased burden (P = 2.6 x 10-17) relative to controls. Microdeletions affecting either a gene previously implicated in neurodevelopmental disorders (P = 8.0 x 10-18, OR = 4.6) or an evolutionarily conserved brain-expressed gene related to autism spectrum disorder (P = 1.3 x 10-12, OR = 4.1) were significantly enriched in the GGE patients. Microdeletions found only in GGE patients harboured a high proportion of genes previously associated with epilepsy and neuropsychiatric disorders (NRXN1, RBFOX1, PCDH7, KCNA2, EPM2A, RORB, PLCB1). Our results demonstrate that the significantly increased burden of large and rare microdeletions in GGE patients is largely confined to recurrent hotspot microdeletions and microdeletions affecting neurodevelopmental genes, suggesting a strong impact of fundamental neurodevelopmental processes in the pathogenesis of common GGE syndromes.

Efficacy of the epilepsy nurse: Results of a randomized controlled study.

OBJECTIVE: We investigated the efficacy of epilepsy nurses on satisfaction with counseling about epilepsy in a randomized, controlled, prospective trial. METHODS: Patients with epilepsy treated by neurologists in outpatient clinics were consecutively enrolled and randomly allocated to either the epilepsy nurse (EN) group (n = 92) or the control group (n = 95). Patients in the EN group were advised according to their needs by epilepsy nurses. The control group received routine care without additional counseling. The EN group completed the questionnaires before the first consultation (T1) and 6 months later (T2); the control group completed the questionnaires twice with an interval of 6 months. Primary outcome measure was satisfaction of patients with information and support. Secondary outcome measures were satisfaction with patient-doctor relationship, organization of treatment, epilepsy knowledge, coping, and restrictions in daily life. Anxiety and depression (Hospital Anxiety and Depression Scale) and global Quality of Life (item from QOLIE-31) were also assessed. Statistical analysis included generalized estimating equation (GEE) and nonparametric tests. RESULTS: Satisfaction with information and support improved significantly in the EN group compared to the control group (GEE, interaction group × time, p = 0.001). In addition, Epilepsy Knowledge (p = 0.014) and Coping (subscale Information Seeking) (p = 0.023) improved. Increase in satisfaction with counseling was dependent on patients' needs for information and on the amount of received information (Jonckheere-Terpstra test, p < 0.001). No differences between the groups were observed on other epilepsy-specific scales. SIGNIFICANCE: A reliable questionnaire for satisfaction with epilepsy care has been developed. Epilepsy nurses improve the satisfaction of patients with counseling and information about epilepsy and concomitant problems.

A randomized, double-blind comparison of antiepileptic drug treatment in the elderly with new-onset focal epilepsy.

OBJECTIVE: To compare the effectiveness of controlled-released carbamazepine (CR-CBZ) to levetiracetam (LEV) and to lamotrigine (LTG) in elderly patients with newly diagnosed focal epilepsy. METHODS: Randomized, double-blind, parallel-group trial conducted between January 2007 and August 2011, in 47 ambulatory or hospital sites in Germany, Austria, or Switzerland. Eligible participants were aged ≥ 60, had new-onset epilepsy, had no acute illness as the cause of their seizures, and had no contraindication to the drugs in the trial. Patients were randomized 1:1:1 to CR-CBZ, LTG, or LEV. Doses were up-titrated for 6 weeks and could be maintained or adjusted depending on seizure relapse or tolerability over an additional period of 52 weeks. Primary outcome was the retention to treatment at week 58; secondary measures related to seizure and adverse event frequency. RESULTS: Of 361 randomized patients, 359 were included (CR-CBZ n = 121, LTG n = 117, LEV n = 122) in the modified intent-to-treat population (mean age [range] 71.4 [60-95] years). At week 58, the retention rate for LEV was significantly higher than for CR-CBZ (61.5% vs. 45.8%, p = 0.02), and similar to LTG (55.6%). Seizure freedom rates at weeks 30 and 58 were not different across the groups. Twice as many patients receiving CR-CBZ discontinued due to adverse events or death compared to those in the LEV group (32.2% vs. 17.2%; odds ratio 2.28, 95% confidence interval [CI] 1.25-4.19, p = 0.007), whereas discontinuation was intermediate for LTG (26.3%). Median daily doses of completers (n = 195) were CR-CBZ 380.0 mg/day (333.0-384.0), LTG 95 mg/day (94.0-97.0), and LEV 950 mg/day (940.0-985.0). SIGNIFICANCE: In the initial monotherapy of focal epilepsy in the elderly, 1-year retention to LEV was higher compared to CR-CBZ due to better tolerability. Retention of LTG was intermediate and close to LEV, but did not differ significantly from either comparators. NCT00438451, www.clinicaltrials.gov.

Genome-wide association analysis of genetic generalized epilepsies implicates susceptibility loci at 1q43, 2p16.1, 2q22.3 and 17q21.32.

Genetic generalized epilepsies (GGEs) have a lifetime prevalence of 0.3% and account for 20-30% of all epilepsies. Despite their high heritability of 80%, the genetic factors predisposing to GGEs remain elusive. To identify susceptibility variants shared across common GGE syndromes, we carried out a two-stage genome-wide association study (GWAS) including 3020 patients with GGEs and 3954 controls of European ancestry. To dissect out syndrome-related variants, we also explored two distinct GGE subgroups comprising 1434 patients with genetic absence epilepsies (GAEs) and 1134 patients with juvenile myoclonic epilepsy (JME). Joint Stage-1 and 2 analyses revealed genome-wide significant associations for GGEs at 2p16.1 (rs13026414, P(meta) = 2.5 × 10(-9), OR[T] = 0.81) and 17q21.32 (rs72823592, P(meta) = 9.3 × 10(-9), OR[A] = 0.77). The search for syndrome-related susceptibility alleles identified significant associations for GAEs at 2q22.3 (rs10496964, P(meta) = 9.1 × 10(-9), OR[T] = 0.68) and at 1q43 for JME (rs12059546, P(meta) = 4.1 × 10(-8), OR[G] = 1.42). Suggestive evidence for an association with GGEs was found in the region 2q24.3 (rs11890028, P(meta) = 4.0 × 10(-6)) nearby the SCN1A gene, which is currently the gene with the largest number of known epilepsy-related mutations. The associated regions harbor high-ranking candidate genes: CHRM3 at 1q43, VRK2 at 2p16.1, ZEB2 at 2q22.3, SCN1A at 2q24.3 and PNPO at 17q21.32. Further replication efforts are necessary to elucidate whether these positional candidate genes contribute to the heritability of the common GGE syndromes.

Therapeutic strategies during cenobamate treatment initiation: Delphi panel recommendations.

The goal of epilepsy treatment is seizure freedom, typically with antiseizure medication (ASM). If patients fail to attain seizure control despite two trials of appropriately chosen ASMs at adequate doses, they are classified as having drug-resistant epilepsy (DRE). Adverse events (AEs) commonly occur in people with DRE because they are typically on ⩾2 ASMs, increasing the potential for drug-drug interactions. Early emerging AEs may impact adherence, decrease quality of life, and delay achieving optimal treatment dosages. Cenobamate is an oral ASM with a long half-life which has proven to be highly effective in clinical trials. An international Delphi panel of expert epileptologists experienced in the clinical use of cenobamate and other ASMs was convened to develop consensus best practices for managing patients during and after cenobamate titration, with consideration for its known pharmacokinetic and pharmacodynamic interactions, to allow patients to reach the most appropriate cenobamate dose while limiting tolerability issues. The modified Delphi process included one open-ended questionnaire and one virtual face-to-face meeting. Participants agreed that cenobamate can be prescribed for most patients experiencing focal-onset seizures. Patients initiating cenobamate therapy should have access to healthcare professionals as needed and their treatment response should be evaluated at the 100-mg dose. Patients with intellectual disabilities may need additional support to navigate the titration period. Proactive down-titration or withdrawal of sodium channel blockers (SCBs) is recommended when concomitant ASM regimens include ⩾2 SCBs. When applicable, maintaining a concomitant clobazam dose at ~5-10 mg may be beneficial. Patients taking oral contraceptives, newer oral anticoagulants, or HIV antiretroviral medications should be monitored for potential interactions. Because clinical evidence informing treatment decisions is limited, guidance regarding dose adjustments of non-ASM drugs was not developed beyond specific recommendations presented in the Summary of Product Characteristics.

A multicenter randomized controlled feasibility trial of a digital self-management intervention for adults with epilepsy.

OBJECTIVE: Self-management interventions may enhance health-related quality of life (HRQoL) in epilepsy. However, several barriers often impair their implementation in the real world. Digital interventions may help to overcome some of these barriers. Considering this, the Helpilepsy Plus Prototype was developed as a prototype smartphone-delivered self-care treatment program for adults with epilepsy. METHODS: The 12-week Helpilepsy Plus Prototype was evaluated through a randomized controlled feasibility trial with a waiting-list control (WLC) group. Outcome measurement at baseline and at 12 weeks assessed adherence to the prototype intervention and changes in epilepsy-related outcomes. The primary endpoint was patient autonomy measured with EASE, and secondary endpoints included HRQoL measured with QOLIE-31, health literacy measured with HLQ, anxiety, and depression symptoms measured with HADS. Semi-structured interviews were conducted with a heterogeneous sample of participants to assess user-friendliness and usefulness. The prototype program was delivered through the Neuroventis Platform (Neuroventis, BV, Overijse, Belgium), a certified medical device (under EU/MDD Class I, and EU/MDR grace period). RESULTS: Ninety-two patients were included (46 in the intervention group, 46 in WLC). Most participants (63%, 58/92 women, median age 30 years) had pharmacoresistant epilepsy (61%, 56/92). Only 22% of participants (10/46) in the intervention group completed at least half of all intervention sessions. No significant differences between the intervention group and WLC were observed. Although there was a larger proportion of patients in the intervention group with meaningful improvements in HRQoL compared to WLC (19/46 versus 11/46), the difference was not significant (p = 0.119). Qualitative feedback showed that participants would appreciate more personalization, such as adaptation of the content to their current epilepsy knowledge level, a more interactive interface, shorter text sections, and interaction through reminders and notifications. SIGNIFICANCE: Digital interventions should allow sufficient scope for personalization and interaction to increase patient engagement and enable benefits from self-care apps. Feedback loops allow the participatory development of tailored interventions. PLAIN LANGUAGE SUMMARY: In this study, we investigated the effectiveness of an app-based self-help intervention. Study participants were either randomly assigned to a group that had access to the app or a group that received access to the app after the end of the study. Although a larger proportion of participants in the intervention group showed a relevant improvement in quality of life, the difference between the two groups was not statistically significant. Less than one-fifth of participants in the intervention group attended at least half of all intervention sessions; patient feedback showed that patients required more personalization and interactive options.

Treatment of postsurgical psychiatric complications.

We describe the physical, psychological, and social complications and adaptation demands after epilepsy surgery and the risks of the development of psychiatric disorders when adequate stress processing fails. Practical strategies that can be followed in the prevention and treatment of postsurgical psychiatric complications are reviewed. The postoperative period is divided in three phases: (1) the early postoperative phase of stress processing until discharge from hospital; (2) the coping phase during the first months after discharge; and (3) the reorientation phase. The early postoperative course is often dominated by physical problems that hamper success in convalescence. They may initiate early psychiatric disturbances especially in patients with preoperative psychiatric comorbidity. The second phase after discharge from hospital is the typical time in which various psychiatric disorders may develop (either de novo or exacerbations of known disorders). At this time it is mandatory to keep in contact with patients, to start psychiatric treatments if necessary, and to assess for suicidal risk. The course of the third phase of reorientation depends on seizure outcome and on psychiatric state. Seizure-free persons without psychiatric comorbidities start to forget their epilepsy; those with less successful outcome conditions may need further support, especially for vocational integration. Epilepsy surgery brings about an overall strong improvement of psychiatric morbidity and quality of patients' life. Nevertheless, the first postoperative year is a fragile period that includes multiple physical, psychological, and social adaptation tasks. Patients with a history of psychiatric disorders are at a special risk of failing to cope with those health-related demands, but also for nonpsychiatric patients the months after epilepsy surgery are often stressful and exhausting. Professional help must be available during the postoperative coping time.

Antiepileptic drugs and suicidality: an expert consensus statement from the Task Force on Therapeutic Strategies of the ILAE Commission on Neuropsychobiology.

In 2008, the U.S. Food and Drug Administration (FDA) issued an alert to health care professionals about an increased risk of suicide ideation and suicide behavior in people treated with antiepileptic drugs (AEDs). Since then, a number of retrospective cohort and case-control studies have been published that are trying to address this issue, but gathered results are contradictory. This report represents an expert consensus statement developed by an ad hoc task force of the Commission on Neuropsychobiology of the International League Against Epilepsy (ILAE). Although some (but not all) AEDs can be associated with treatment-emergent psychiatric problems that can lead to suicidal ideation and behavior, the actual suicidal risk is yet to be established, but it seems to be very low. The risk of stopping AEDs or refusing to start AEDs is significantly worse and can actually result in serious harm including death to the patient. Suicidality in epilepsy is multifactorial, and different variables are operant. Clinicians should investigate the existence of such risk factors and adopt appropriate screening instruments. If necessary, patients should be referred for a psychiatric evaluation, but AED treatment should not be withheld, even in patients with positive suicidal risks. When starting an AED or switching from one to other AEDs, patients should be advised to report to their treating physician any change in mood and suicidal ideation. Data on treatment-emergent psychiatric adverse events need to be collected, in addition to general safety information, during controlled studies in order to have meaningful information for patients and their relatives when a new drug is marketed.

Neuropsychology and behavior in juvenile myoclonic epilepsy.

Following decades of neglect, there has been an increasing interest in the behavioral aspects of juvenile myoclonic epilepsy (JME) in the recent literature. A number of authors have investigated psychiatric comorbidity, cognitive profiles, and related behavioral features associated with JME. Although these findings are not entirely uniform, most studies suggest an increased incidence in psychiatric comorbidity and specific cognitive deficits that explain some of the clinical observations of poor compliance and other unhealthy behaviors in people suffering from JME. Neuropsychological profiles in JME are suggestive of subtle frontal dysfunctions, and some of the observations have been linked with sophisticated structural and functional imaging findings. Taken together, there is evidence that JME is associated with dysfunctions in networks linking motor and cognitive neuronal centers. Interestingly, there is evidence from family studies that the behavioral abnormalities in JME are genetically determined, suggesting an underlying developmental disorder.

Management of juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME) is a common form of epilepsy and a fairly lifelong disorder that may significantly lower a patient's expectations and potential for a full life. Luckily, it is also a highly treatable disorder, and up to 85% of patients with JME will enjoy satisfactory seizure control. Among anticonvulsants, valproate still stands out as the most efficacious drug, but may be poorly tolerated by some, and is considered unsafe for the fetuses of pregnant women. Alternatives have emerged in recent years, especially levetiracetam, but also topiramate, zonisamide or lamotrigine. In some cases, combination therapy may be useful or even required. One should not forget the potential aggravation induced not only by some commonly used anticonvulsants, especially carbamazepine and oxcarbazepine, but also, in some patients, by lamotrigine. In special settings, older drugs like benzodiazepines and barbiturates may be useful. But the management of JME should also include intervention in lifestyle, with strict avoidance of sleep deprivation and the management of copathologies, including the cognitive and psychiatric problems that are often encountered. With adequate management, there will only remain a small proportion of patients with uncontrolled epilepsy and all of its related problems. Juvenile myoclonic epilepsy is a condition in which the clinician has a fair chance of significantly helping the patient with medication and counseling.

Consensus on diagnosis and management of JME: From founder's observations to current trends.

An international workshop on juvenile myoclonic epilepsy (JME) was conducted in Avignon, France in May 2011. During that workshop, a group of 45 experts on JME, together with one of the founding fathers of the syndrome of JME ("Janz syndrome"), Prof. Dr. Dieter Janz from Berlin, reached a consensus on diagnostic criteria and management of JME. The international experts on JME proposed two sets of criteria, which will be helpful for both clinical and scientific purposes. Class I criteria encompass myoclonic jerks without loss of consciousness exclusively occurring on or after awakening and associated with typical generalized epileptiform EEG abnormalities, with an age of onset between 10 and 25. Class II criteria allow the inclusion of myoclonic jerks predominantly occurring after awakening, generalized epileptiform EEG abnormalities with or without concomitant myoclonic jerks, and a greater time window for age at onset (6-25years). For both sets of criteria, patients should have a clear history of myoclonic jerks predominantly occurring after awakening and an EEG with generalized epileptiform discharges supporting a diagnosis of idiopathic generalized epilepsy. Patients with JME require special management because their epilepsy starts in the vulnerable period of adolescence and, accordingly, they have lifestyle issues that typically increase the likelihood of seizures (sleep deprivation, exposure to stroboscopic flashes in discos, alcohol intake, etc.) with poor adherence to antiepileptic drugs (AEDs). Results of an inventory of the different clinical management strategies are given. This article is part of a supplemental special issue entitled Juvenile Myoclonic Epilepsy: What is it Really?