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.

[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.

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.

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.

Cenobamate in refractory epilepsy: Overview of treatment options and practical considerations.

Management of drug resistant epilepsy (DRE) represents a challenge to the treating clinician. This manuscript addresses DRE and provides an overview of treatment options, medical, surgical, and dietary. It addresses treatment strategies in polytherapy, then focuses on the role cenobamate (CNB) may play in reducing the burden of DRE while providing practical advice for its introduction. CNB is a recently approved, third generation, anti-seizure medication (ASM), a tetrazole-derived carbamate, thought to have a dual mechanism of action, through its effect on sodium channels as well as on GABAA receptors at a non-benzodiazepine site. CNB, having a long half-life, is an effective add-on ASM in refractory focal epilepsy with a higher response rate and a higher seizure-freedom rate than is usually seen in regulatory clinical trials. Experience post-licensing, though still limited, supports the findings of clinical trials and is encouraging. Its spectrum of action in relation to generalized epilepsies and seizures remains to be established, and there are no data on its efficacy in monotherapy. At the time of writing, CNB has been prescribed for some 50 000 individuals with DRE and focal epilepsy. A larger number is needed to fully establish its safety profile. It should at all times be introduced slowly to minimize the risk of serious allergic drug reactions. It has clinically meaningful interactions which must be anticipated and managed to maximize tolerability and likelihood of successful treatment. Despite the above, it may well prove to be of major benefit in the treatment of many patients with drug resistant epilepsy.

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.

Persistent knowledge gaps between 2005 and 2020 in women with epilepsy: Comparison of multicenter studies from Germany.

OBJECTIVE: Epilepsy is a chronic condition that can affect patients of all ages. Women with epilepsy (WWE) require access to specific counseling and information regarding issues related to contraception, pregnancy, and hormonal effects on seizure control and bone mineral density. This study investigated the knowledge among WWE regarding their condition, and whether epilepsy-specific knowledge has improved over the last 15 years. METHODS: A total of 280 WWE aged 18 to 82 years participated in this multicenter, questionnaire-based study. The study was conducted at four epilepsy centers in Germany, between October 2020 and December 2020. Sociodemographic and epilepsy-specific data for participating women were analyzed and compared with the results of a similar survey performed in 2003-2005 among 365 WWE in Germany. RESULTS: The questionnaire-based survey revealed considerable knowledge deficits without significant improvements over the last 15 years, particularly among those with less education and with regards to information on the more pronounced effects of epilepsy in older WWE (>50 years), including interactions with menopause and osteoporosis. In WWE ≤29 years, a significant increase in the knowledge score was observed in 2020 compared with this age group in 2005 (mean 7.42 vs. 6.5, p = .036). Mothers frequently reported epilepsy-related concerns regarding childrearing, particularly of seizures scaring their child and the need to rely on other people. CONCLUSION: WWE continue to demonstrate inadequate epilepsy-related knowledge. Despite increasing information availability and the aspiration toward better awareness among medical professionals, overall knowledge has not increased sufficiently compared with the levels observed in recent studies.

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.

Expert opinion: use of valproate in girls and women of childbearing potential with epilepsy: recommendations and alternatives based on a review of the literature and clinical experience-a European perspective.

Valproate is a broad-spectrum antiepileptic drug (AED) of particular interest in pediatric epilepsy syndromes and idiopathic generalized epilepsy, as it is relatively more effective in these syndromes than other AEDs. In 2018, the European Medicines Agency introduced new restrictions on the use of valproate in girls and women of childbearing potential to avoid exposure during pregnancy. The strengthening of existing restrictions sparked controversy and debate among patients and the medical community. The high prevalence of epilepsy syndromes amenable to valproate treatment in women of childbearing age and the little information available on the teratogenic potential of alternative treatments have created uncertainty on how to manage these patients. In this consensus statement, based on a review of the literature and the clinical experience of a panel of European epilepsy experts, we present general recommendations for the optimal clinical management of AED treatment in girls, women of childbearing potential, and pregnant women across the different epilepsy syndromes.

Could the 2017 ILAE and the four-dimensional epilepsy classifications be merged to a new "Integrated Epilepsy Classification"?

Over the last few decades the ILAE classifications for seizures and epilepsies (ILAE-EC) have been updated repeatedly to reflect the substantial progress that has been made in diagnosis and understanding of the etiology of epilepsies and seizures and to correct some of the shortcomings of the terminology used by the original taxonomy from the 1980s. However, these proposals have not been universally accepted or used in routine clinical practice. During the same period, a separate classification known as the "Four-dimensional epilepsy classification" (4D-EC) was developed which includes a seizure classification based exclusively on ictal symptomatology, which has been tested and adapted over the years. The extensive arguments for and against these two classification systems made in the past have mainly focused on the shortcomings of each system, presuming that they are incompatible. As a further more detailed discussion of the differences seemed relatively unproductive, we here review and assess the concordance between these two approaches that has evolved over time, to consider whether a classification incorporating the best aspects of the two approaches is feasible. To facilitate further discussion in this direction we outline a concrete proposal showing how such a compromise could be accomplished, the "Integrated Epilepsy Classification". This consists of five categories derived to different degrees from both of the classification systems: 1) a "Headline" summarizing localization and etiology for the less specialized users, 2) "Seizure type(s)", 3) "Epilepsy type" (focal, generalized or unknown allowing to add the epilepsy syndrome if available), 4) "Etiology", and 5) "Comorbidities & patient preferences".

Tolerability and efficacy of lacosamide and controlled-release carbamazepine monotherapy in patients with newly diagnosed epilepsy and concomitant psychiatric conditions: Post hoc analysis of a prospective, randomized, double-blind trial.

Psychiatric comorbidities are common in patients with epilepsy. A double-blind noninferiority monotherapy trial (SP0993; NCT01243177) enrolled newly diagnosed patients (≥16 years) with focal or generalized tonic-clonic seizures. Patients were randomized 1:1 to lacosamide or carbamazepine controlled-release (carbamazepine-CR). Here, we report data from an exploratory post hoc analysis of patients who reported ongoing psychiatric conditions (Medical Dictionary for Regulatory Activities System Organ Class). Of 886 treated patients in the trial, 126 (14.2%; 64 on lacosamide; 62 on carbamazepine-CR) reported at least one ongoing psychiatric condition at screening, most commonly depression (38.1%), insomnia (27.8%), and anxiety (26.2%). In this subgroup, 32/64 (50.0%) patients on lacosamide and 22/62 (35.5%) on carbamazepine-CR completed the trial. The most common reasons for discontinuation in patients on lacosamide and carbamazepine-CR were adverse events (10.9%, 24.2%) and lack of efficacy (18.8%, 11.3%). Treatment-emergent adverse events (TEAEs) were reported in 52 (81.3%) of patients on lacosamide and 56 (90.3%) of patients on carbamazepine-CR, most commonly (≥10% patients in either treatment group; lacosamide, carbamazepine-CR) dizziness (12.5%, 16.1%), headache (12.5%, 14.5%), nasopharyngitis (12.5%, 9.7%), fatigue (7.8%, 14.5%), nausea (7.8%, 11.3%), somnolence (1.6%, 12.9%), and gamma-glutamyltransferase increase (1.6%, 12.9%). Overall, 15 (23.4%) lacosamide-treated and 10 (16.1%) carbamazepine-CR treated patients reported psychiatric TEAEs, most commonly (≥3 patients in either treatment group; lacosamide, carbamazepine-CR) depression (4.7%, 0) and anxiety (3.1%, 6.5%). There were no reports of psychotic disorder, epileptic psychosis, acute psychosis, or serious psychiatric TEAEs. Stratified Kaplan-Meier estimates for 6- and 12-month seizure freedom at the last evaluated dose were similar with lacosamide and carbamazepine-CR (6 months 81.0%, 75.6%; 12 months 62.5%, 66.6%). A higher proportion of patients on lacosamide than carbamazepine-CR completed 6 (67.2%, 45.2%) and 12 months (50.0%, 37.1%) of treatment at the last evaluated dose without a seizure. This exploratory post hoc analysis indicated that lacosamide monotherapy was efficacious and generally well tolerated in patients with newly diagnosed epilepsy and concomitant psychiatric conditions. In this subpopulation, lacosamide showed similar efficacy and numerically better effectiveness than carbamazepine-CR.

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.

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.

Juvenile myoclonic epilepsy: A system disorder of the brain.

The prevailing understanding of generalized epilepsy is shaped by the traditional definition that "the responsible neuronal discharge takes place, if not throughout the entire grey matter, then at least in the greater part of it and simultaneously on both sides". This view is no longer tenable since concurrent findings using multiple methods have accumulated to reveal the role of bilateral networks of distributed and selective cortical and subcortical structures in so-called generalized ictogenesis. Most of this research has been focused on juvenile myoclonic epilepsy (JME), which today is commonly considered the archetypical syndrome of the idiopathic generalized epilepsies. Based upon recent research in the fields of clinical epileptology, neuropsychology and psychiatry, clinical neurophysiology, neuroimaging and epilepsy genetics this article, for the first time, unites these new findings into a comprehensive nosological view. Genetically determined dysfunctions of important cognitive systems like visuomotor coordination and linguistic communication appear now as key mechanisms of seizure generation in JME. This review suggests a new paradigm to consider JME as a system disorder of the brain analogous to other neurological system disorders.

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.

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.