Laurent M. Willems

Perampanel in the treatment of focal and idiopathic generalized epilepsies and of status epilepticus

Perampanel is the latest approved antiepileptic drug in focal and generalized epilepsies and has a distinct and selective mode of action on AMPA-receptors. Several thousand patients have received perampanel within randomized placebo-controlled trials, open-label extension trials and post-marketing observational studies. Significant median partial-onset seizure reduction rates of 23% for 4 mg/day, 26–31% for 8 mg/day and 18–35% for 12 mg/day were reported. Likewise 50 percent responder rates were 29% for 4 mg/day, 33–38% for 8 mg/day and 34–36% for 12 mg/day. Primary generalized tonic–clonic seizures were reduced by 76.5% (8 mg) vs 38.4% (placebo) in a recent controlled trial. Overall, perampanel is well tolerated and the main adverse events are dizziness, somnolence and fatigue. There are also anecdotal reports on use in progressive myoclonic epilepsies and status epilepticus. Perampanel will likely remain an important, possibly broad-spectrum AED with a significant market share, especially in patients with drug-refractory epilepsies.

Postmarketing experience with brivaracetam in the treatment of epilepsies: A multicenter cohort study from Germany

To evaluate factors predicting efficacy, retention, and tolerability of add‐on brivaracetam (BRV) in clinical practice.

Lacosamide in status epilepticus: Systematic review of current evidence

The intravenous formulation of lacosamide (LCM) and its good overall tolerability and safety favor the use in status epilepticus (SE). The aim of this systematic review was to identify and evaluate studies reporting on the use of LCM in SE.

Treatment of refractory and super-refractory status epilepticus with brivaracetam: A cohort study from two German university hospitals

PURPOSE We aimed to ascertain the possible use of brivaracetam (BRV) as an option for treatment of status epilepticus (SE). METHODS A review of medical records was carried out to detect BRV administration in SE patients treated in Frankfurt and Greifswald during the period February 2016 to January 2017. The primary outcome question concerned SE resolution after BRV initiation. RESULTS During that period, BRV was started with eleven adult patients with SE. Five of these were female, and the median age was 64 (interquartile range [IQR] 21years). The median SE duration before BRV initiation was 5days (IQR 9days); the median number of previous anticonvulsants used was 4 (IQR 5). Initial BRV doses ranged between 50mg and 400mg (median 100mg), titrated to a daily dose of 100 to 400mg (median 200mg). There was a cessation of SE in the first 24h of BRV in three patients (27%). While taking BRV, no serious side effects were seen. CONCLUSION Based on these cases and previous data from animal experiments, BRV may prove useful in SE treatment, and trials would be warranted to examine BRVs efficacy in treating SE and how this efficacy might be influenced by co-administration with levetiracetam.

Functional and Structural Properties of Dentate Granule Cells with Hilar Basal Dendrites in Mouse Entorhino-Hippocampal Slice Cultures

During postnatal development hippocampal dentate granule cells (GCs) often extend dendrites from the basal pole of their cell bodies into the hilar region. These so-called hilar basal dendrites (hBD) usually regress with maturation. However, hBDs may persist in a subset of mature GCs under certain conditions (both physiological and pathological). The functional role of these hBD-GCs remains not well understood. Here, we have studied hBD-GCs in mature (≥18 days in vitro) mouse entorhino-hippocampal slice cultures under control conditions and have compared their basic functional properties (basic intrinsic and synaptic properties) and structural properties (dendritic arborisation and spine densities) to those of neighboring GCs without hBDs in the same set of cultures. Except for the presence of hBDs, we did not detect major differences between the two GC populations. Furthermore, paired recordings of neighboring GCs with and without hBDs did not reveal evidence for a heavy aberrant GC-to-GC connectivity. Taken together, our data suggest that in control cultures the presence of hBDs on GCs is neither sufficient to predict alterations in the basic functional and structural properties of these GCs nor indicative of a heavy GC-to-GC connectivity between neighboring GCs.

The efficacy of lacosamide as monotherapy and adjunctive therapy in focal epilepsy and its use in status epilepticus: clinical trial evidence and experience:

Lacosamide (LCM) is approved for anticonvulsive treatment in focal epilepsy and exhibits its function through the slow inactivation of voltage-gated sodium channels (VGSCs). LCM shows comparable efficacy with other antiepileptic drugs (AEDs) licensed in the last decade: in three randomized placebo-controlled trials, significant median seizure reduction rates of 35.2% for 200 mg/day, 36.4–39% for 400 mg/day and 37.8–40% for 600 mg/day were reported. Likewise, 50% responder rates were 38.3–41.1% for 400 mg/day and 38.1–41.2% for 600 mg/day. Similar rates were reported in post-marketing studies. The main adverse events (AEs) are dizziness, abnormal vision, diplopia and ataxia. Overall, LCM is well tolerated and has no clinically-relevant drug–drug interactions. Due to the drug’s intravenous availability, its use in status epilepticus (SE) is increasing, and the available data are promising.

Use of brivaracetam in genetic generalized epilepsies and for acute, intravenous treatment of absence status epilepticus

The objective of this study was to evaluate effectiveness, retention, and tolerability of brivaracetam (BRV) in genetic generalized epilepsies (GGE) in clinical practice.

Incidence, Risk Factors and Consequences of Epilepsy-Related Injuries and Accidents: A Retrospective, Single Center Study

Introduction: This study was designed to evaluate risk factors and incidence of epilepsy-related injuries and accidents (ERIA) at an outpatient clinic of a German epilepsy center providing healthcare to a mixed urban and rural population of over one million inhabitants. Methods: Data acquisition was performed between 10/2013 and 09/2014 using a validated patient questionnaire on socioeconomic status, course of epilepsy, quality of life (QoL), depression, injuries and accidents associated with seizures or inadequate periictal patterns of behavior concerning a period of 3 months. Univariate analysis, multiple testing and regression analysis were performed to identify possible variables associated with ERIA. Results: A total of 292 patients (mean age 40.8 years, range 18–86; 55% female) were enrolled and analyzed. Focal epilepsy was diagnosed in 75% of the patients. The majority was on an antiepileptic drug (AEDs) polytherapy (mean number of AEDs: 1.65). Overall, 41 patients (14.0%) suffered from epilepsy-related injuries and accidents in a 3-month period. Besides lacerations (n = 18, 6.2%), abrasions and bruises (n = 9, 3.1%), fractures (n = 6, 2.2%) and burns (n = 3, 1.0%), 17 mild injuries (5.8%) were reported. In 20 (6.8% of the total cohort) cases, urgent medical treatment with hospitalization was necessary. Epilepsy-related injuries and accidents were related to active epilepsy, occurrence of generalized tonic-clonic seizures (GTCS) and drug-refractory course as well as reported ictal falls, ictal loss of consciousness and abnormal peri-ictal behavior in the medical history. In addition, patients with ERIA had significantly higher depression rates and lower QoL. Conclusion: ERIA and their consequences should be given more attention and standardized assessment for ERIA should be performed in every outpatient visit.

Eslicarbazepine acetate in epilepsies with focal and secondary generalised seizures: systematic review of current evidence

ABSTRACT Introduction: Eslicarbazepine acetate (ESL) is a third-generation antiepileptic drug (AED) approved for adjunctive treatment in adults, children, and adolescents with focal-onset seizures. Recently ESL was approved for initial monotherapy in adults. The intention of this article is to review current evidence for ESL and to summarise its pharmacological profile in comparison to other AEDs of the dibenzazepine group. Areas covered: We performed a systematic literature search in electronic databases (MEDLINE database, Cochrane Central Register of Controlled Trials, Excerpta Medica dataBASE) using a combined search strategy including the following keywords: eslicarbazepine, epilepsy and seizure. The search was performed from 2000 until December 2017. Using a standardised assessment form, information on the study design, methodological framework, data sources and efficacy and adverse events attributed to ESL were extracted from each publication and systematically reported. Expert commentary: ESL is an effective, safe and well tolerated third-generation AED for the treatment of focal epilepsies. During therapy, especially serum sodium levels and possible interactions with other substances have to be monitored. As of yet, long-term experience is still needed to make severe late-occurring adverse events unlikely and to obtain data regarding its use in pregnancy.

Noncompliance of patients with driving restrictions due to uncontrolled epilepsy

Epilepsies are a common and chronic neurological disorder characterized by sustained risk of recurrent seizures. Because of paroxysmal and often unpredictable occurrence of seizures, patients with uncontrolled epilepsy are subject to disease-specific restrictions in daily life, such as their career choice or specific work limitations. According to German law and many other European and international guidelines, driving is strictly prohibited in patients with uncontrolled epilepsy so as to increase active and passive safety in public road traffic. Nevertheless, a significant percentage of patients probably do not comply with these legal restrictions and drive on a regular basis. For this study, we analyzed a representative German cohort with 302 patients (mean age: 45.0 years ± 16.4; 48% male) with established epilepsy to identify the number of patients driving without permission. Overall, 58.6% (n = 177) of patients had a driving license, 71.1% (n = 69/97) of patients were in seizure remission, and 52.7% (n = 108/205) of patients had uncontrolled epilepsy. Among patients in seizure remission, 54.6% (n = 53/97) reported regular driving while, among patients with uncontrolled epilepsy, 15.1% (n = 31/205) reported driving on a regular basis. No patient in the cohort stated driving without a valid license. Permanent employment, freelance work, the absence of a relevant disability, and living alone were identified as significant risk factors, which underlines the already existing evidence for the importance of a possible restricted access to the labor market as motive for disregarding legal driving restrictions. In our opinion, specialized and generally available social counseling with a special focus on vocational and career guidance is urgently needed to improve compliance with epilepsy-caused driving restrictions and the underlying reasons for violating these rules. In addition, more effort has to be spent on improving diagnostics and treatment of epilepsy to reduce the number of patients with uncontrolled seizures. Comprehensive introduction of self-driving vehicles may also help to improve mobility of patients with refractory epilepsy.