Search

Status epilepticus (SE) is an acute, life-threatening medical condition that requires immediate, effective therapy. Therefore, the acute care of prolonged seizures and SE is a constant challenge for healthcare professionals, in both the pre-hospital and the in-hospital settings. Benzodiazepines (BZDs) are the first-line treatment for SE worldwide due to their efficacy, tolerability, and rapid onset of action. Although all BZDs act as allosteric modulators at the inhibitory gamma-aminobutyric acid (GABA)subA/subreceptor, the individual agents have different efficacy profiles and pharmacokinetic and pharmacodynamic properties, some of which differ significantly. The conventional BZDs clonazepam, diazepam, lorazepam and midazolam differ mainly in their durations of action and available routes of administration. In addition to the common intravenous, intramuscular and rectal administrations that have long been established in the acute treatment of SE, other administration routes for BZDs-such as intranasal administration-have been developed in recent years, with some preparations already commercially available. Most recently, the intrapulmonary administration of BZDs via an inhaler has been investigated. This narrative review provides an overview of the current knowledge on the efficacy and tolerability of different BZDs, with a focus on different routes of administration and therapeutic specificities for different patient groups, and offers an outlook on potential future drug developments for the treatment of prolonged seizures and SE.

Status epilepticus is a frequent neurological emergency associated with a case fatality of about 10-15% depending on age, cause, and other factors, and a high burden for patients, caregivers, and society. In pregnancy, it can occur in two different clinical constellations: (1) In women with a history of epilepsy and (2) as new onset status epilepticus in pregnancy (NOSEP). Both entities are relatively rare but differ in terms of etiology. Here we describe the epidemiology, etiologies, diagnosis, clinical course with the maternal and fetal outcome, and the suggested management strategies for either manifestation. This paper was presented at the 8th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures held in September 2022.

Epilepsy surgery in low-grade epilepsy-associated neuroepithelial tumors (LEAT) is usually evaluated in drug-resistant cases, often meaning a time delay from diagnosis to surgery. To identify factors predicting good postoperative seizure control and neuropsychological outcome, the cohort of LEAT patients treated with resective epilepsy surgery at the Epilepsy Center Frankfurt Rhine-Main, Germany between 2015 and 2020 was analyzed. Thirty-five patients (19 males (54.3%) and 16 females, aged 4 to 40 years (M = 18.1), mean follow-up 33 months) were included. Following surgery, 77.1% of patients remained seizure-free (Engel IA/ILAE 1). Hippocampus and amygdala resection was predictive for seizure freedom in temporal lobe epilepsy. In total, 65.7% of all patients showed cognitive deficits during presurgical workup, decreasing to 51.4% after surgery, predominantly due to significantly less impaired memory functions (p = 0.011). Patients with presurgical cognitive deficits showed a tendency toward a longer duration of epilepsy (p = 0.050). Focal to bilateral tonic-clonic seizures (p = 0.019) and young age at onset (p = 0.018) were associated with a higher likelihood of cognitive deficits after surgery. Therefore, we advocate early epilepsy surgery without requiring proof of drug-resistance. This refers especially to lesions associated with the non-eloquent cortex.

To evaluate the frequency of reported antiseizure medication (ASM) supply problems among patients with epilepsy (PWE) in Germany.The Epi2020 study was a multicenter study focusing on different healthcare aspects of adult PWE in Germany. In addition to basic clinical and demographic characteristics, PWE were asked to answer a questionnaire regarding supply difficulties regarding their ASM, and if they had to discontinue ASM treatment due to supply problems. Generic switch of medication was recorded, and adverse effects were measured using the Liverpool Adverse Events Profile (LAEP) scale. Data were analyzed to detect predictors of supply problems.In total, 434 PWE with a mean age of 40 years (median 37 years, SD = 15.5, range: 18-83 years, 254 female) participated in this study. 53.7% of PWE (n = 233) reported that at least once in the past 12 months their ASM was not available at the pharmacy, and 24.9% (n = 108) reported having experienced ASM supply problems three times or more during the past 12 months. Patients with epilepsy treated with carbamazepine and zonisamide reported frequent problems with availability in 45.8% and 44.8% respectively, whereas those treated with lacosamide and valproate reported supply problems less frequently (17.0% and 16.4%, respectively). Nine patients (2.1%) were unable to take their ASM as prescribed at least once in the past 12 months due to supply problems. Forty-nine patients (11.3%) reported having to switch ASM due to supply difficulties with generic replacement occurring in 39.4% (n = 171) of patients. Those with supply problems were more likely to be treated with more ASMs and scored higher on the LAEP.Supply problems with ASM are frequent among PWE in Germany and are reported for older and newer ASMs. Supply problems contribute to ASM nonadherence and are positively correlated with the number of ASM taken and adverse events.

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. Copyright © 2022. Published by Elsevier Ltd.

Objective This study was undertaken to evaluate the long-term efficacy, retention, and tolerability of add-on brivaracetam (BRV) in clinical practice. Methods A multicenter, retrospective cohort study recruited all patients who initiated BRV between February and November 2016, with observation until February 2021. Results Long-term data for 262 patients (mean age = 40 years, range = 5-81 years, 129 men) were analyzed, including 227 (87%) diagnosed with focal epilepsy, 19 (7%) with genetic generalized epilepsy, and 16 (6%) with other or unclassified epilepsy syndromes. Only 26 (10%) patients had never received levetiracetam (LEV), whereas 133 (50.8%) were switched from LEV. The length of BRV exposure ranged from 1 day to 5 years, with a median retention time of 1.6 years, resulting in a total BRV exposure time of 6829 months (569 years). The retention rate was 61.1% at 12 months, with a reported efficacy of 33.1% (79/239; 50% responder rate, 23 patients lost-to-follow-up), including 10.9% reported as seizure-free. The retention rate for the entire study period was 50.8%, and at last follow-up, 133 patients were receiving BRV at a mean dose of 222 ± 104 mg (median = 200, range = 25-400), including 52 (39.1%) who exceeded the recommended upper dose of 200 mg. Fewer concomitant antiseizure medications and switching from LEV to BRV correlated with better short-term responses, but no investigated parameters correlated with positive long-term outcomes. BRV was discontinued in 63 (24%) patients due to insufficient efficacy, in 29 (11%) for psychobehavioral adverse events, in 25 (10%) for other adverse events, and in 24 (9%) for other reasons. Significance BRV showed a clinically useful 50% responder rate of 33% at 12 months and overall retention of >50%, despite 90% of included patients having previous LEV exposure. BRV was well tolerated; however, psychobehavioral adverse events occurred in one out of 10 patients. Although we identified short-term response and retention predictors, we could not identify significant predictors for long-term outcomes.

To analyze the concerns and worries about planning to have children and being a parent as a person with epilepsy and investigate gender differences in these perceptions.The Epi2020 study was a large multicenter study focusing on different healthcare aspects of adult patients with epilepsy in Germany. In addition to basic clinical and demographic characteristics, patients were asked to answer a questionnaire regarding their plan to have children, if they had children, and concerns about their children's health. Data were analyzed to detect differences between men and women with epilepsy according to age group.In total, 477 patients with epilepsy with a mean age of 40.5 years (SD = 15.5, range: 18-83 years) participated in this study; 280 (58.7%) were female and 197 (41.3%) were male. Both women and men frequently reported concerns and worries about having children: In the age group below 45 years of age, 72.5% of women and 58.2% of men described being worried to some extent that their children may also suffer from epilepsy (p = .006). Furthermore, 67.3% of women and 54.2% of men below the age of 45 years reported being worried that their children may be disabled (p = .003). Women were more likely to have family members who are reluctant to support their desire to have children (p = .048).Women with epilepsy of childbearing age are significantly more likely to report major concerns that their children might be disabled or also have epilepsy than men with epilepsy and, therefore, express more concerns about choosing to have a child. However, men also report frequent concerns and worries, and this should be addressed not only on request but should be included in the provision of general information on epilepsy.

Objective To investigate benefits of in-hospital, long-term video EEG monitoring (LVEM) for pediatric patients, from a therapeutic perspective and from the perspectives of patients and their families. Methods A monocentric retrospective cohort study was conducted. Patients aged 0–18 years who underwent LVEM for epilepsy surgery eligibility, epilepsy syndrome clarification, or medication adjustment were evaluated regarding paroxysmal event type, change in seizure frequency and patients’ benefits using a standardized evaluation protocol. Results A total of 163 (88 boys and 75 girls, mean age 10.9 years) pediatric patients underwent 178 LVEM sessions, with a mean duration of 5.4 days. The rate of habitual event detection was 69.1%. Epilepsy diagnosis was confirmed in 147 patients and excluded in 16 patients (9.8%). LVEM results altered the diagnosis of 37.4% of patients. Diagnosis remained unchanged in 49.1% of patients and was specified in 13.5% of patients. Epilepsy surgery was performed in 32 patients, and 64% of epilepsy patients deemed ineligible for epilepsy surgery underwent medication adjustments. Patients or their families found LVEM helpful in 75% of cases. Significant seizure reductions and improvements in the disease course were reported by 45% of epilepsy patients. Three episodes of non-convulsive status epilepticus occurred, representing 1.7% of admissions and 1.9% of patients diagnosed with epilepsy, while no injuries were observed. Conclusions LVEM is beneficial for pediatric patients from both a medical perspective and from the perspective of patients and their families, even if patients are ineligible for epilepsy surgery. LVEM is well-tolerated with a low risk of status epilepticus and injuries.

Antiseizure drugs (ASDs) play a central and crucial role in the treatment of epilepsy patients because the majority require anticonvulsant treatment for an extended period of time. Due to the fact that 30% of patients are refractory to medical treatment, new therapeutic options are necessary. Cenobamate is the latest approved antiepileptic drug in focal epilepsy, and its mode of action is thought to be mediated by blocking voltage-gated sodium channels and interaction with the GABAergic system.This article reviews animal studies, pharmacokinetics, pharmacodynamics, and the phase 1 to 3 trials and open-label extension data on cenobamate.Cenobamate has the potential to perform as an important ASD because trial data are indicative of remarkable responder and seizure freedom rates so far not seen with other ASDs. Cenobamate demonstrated significant efficacy at a dosage between 100 and 400 mg per day. The side-effect profile of this drug is comparable to other ASDs and is mainly CNS related; in particular, somnolence, dizziness, headache, diplopia, and nystagmus. However, slow titration is mandatory to decrease the risk of drug rash with eosinophilia and systemic symptoms (DRESS) that was observed in several patients with fast uptitration schemes.

Introduction Patient education is a central component of quality care. Enhancing patient knowledge can improve patients’ quality of life and facilitate successful self-management. We sought to identify patients’ knowledge levels and knowledge gaps regarding epilepsy-related risks, morbidity, and mortality. Methods Adult patients with epilepsy presenting to the university hospitals in Frankfurt, Greifswald, and Marburg between February 2018 and May 2020 were asked to participate in this questionnaire-based study. Results A total of 238 patients (52% women), with a mean age of 39.2 years (range: 18–77 years), participated in this study. Spontaneously, the majority of patients (51.3%) named driving a car, and other traffic-related accidents as possible causes of morbidity and mortality, and 23.9% of patients reported various causes of premature death, such as suffocation, drowning, and respiratory or cardiac arrest due to seizures. Falls due to epilepsy (19.7%) and injuries in general (17.6%) were named as further causes of morbidity and mortality. The vast majority were aware that alcohol (87.4%), sleep deprivation (86.6%), and risky activities in daily life (80.3%) increased the risk of seizure occurrence or increased morbidity and mortality. Regarding overall mortality, 52.1% thought that people with epilepsy were at greater risk of premature death, whereas 46.2% denied this fact to be true. Only 29.4% were aware of status epilepticus, and 27.3% were aware of sudden unexpected death in epilepsy (SUDEP). Driving ability, working ability, and seizure risk were named as major or moderate concerns among patients, but the risk of premature mortality was not a major concern. One-quarter of all patients (26.9%) indicated that they were not counseled about any risk factors or causes of morbidity or mortality by their physicians. Conclusions A lack of knowledge concerning premature mortality, SUDEP, and status epilepticus exists among adult patients with epilepsy. A substantial number of patients indicated that these issues were not discussed adequately by their physicians.

Purpose To describe the patients’ characteristics, surgical ratio, and outcomes following epilepsy surgery at the newly established Epilepsy Center Frankfurt Rhine-Main. Methods We retrospectively studied the first 100 consecutive patients, including adult (n = 77) and pediatric (n = 23) patients, with drug-resistant epilepsy who underwent resective or ablative surgical procedures at a single, newly established epilepsy center. Patient characteristics, seizure and neuropsychological outcomes, histopathology, complications, and surgical ratio were analyzed. Results The mean patient age was 28.8 years (children 10.6 years, adults 34.2 years). The mean epilepsy duration was 11.9 years (children 3.9 years, adults 14.3 years), and the mean follow-up was 1.5 years. At the most recent visit, 64% of patients remained completely seizure free [Engel IA]. The rates of perioperative complications and unexpected new neurological deficits were 5%, each. The proportion of patients showing deficits in one or more cognitive domains increased six months after surgery and decreased to presurgical proportions after two years. Symptoms of depression were significantly decreased and quality of life was significantly increased after surgery. The surgical ratio was 25.3%. Conclusion Similar postsurgical outcomes were achieved at a newly established epilepsy center compared with long-standing epilepsy centers. The lower time to surgery may reflect a general decrease in time to surgery over the last decade or the improved accessibility of a new epilepsy center in a previously underserved area. The surgical ratio was not lower than reported for established centers.