Cenobamate significantly improves seizure control in intellectually disabled patients with drug-resistant epilepsy and allows drug load reduction

IntroductionEpilepsy patients with intellectual disability often suffer from drug-resistant epilepsy (DRE), which severely affects patients’ quality of life. Cenobamate (CNB) is a recently approved novel and effective ASM that can achieve high rates of seizure freedom in previously drug-resistant patients.MethodsWe performed a retrospective data analysis of the first patients treated with CNB at a single center. Outcome and treatment response were assessed at two different time points, and ASM burden was calculated.ResultsA 12 patients (7 males and 5 females) began treatment at a median age of 43 years, six of whom had developmental and epileptic encephalopathies. Prior to treatment with CNB, patients had tried a median of 13 different ASM. At the start of CNB therapy, patients were taking a median of 3 ASM. Treatment outcomes were available for 11 patients. After the first follow-up period (median 9 months), 55% of patients showed a significant seizure reduction of more than 50%, with three patients showing a reduction of more than 75% (27%). One patient achieved complete seizure freedom, while one patient did not respond to treatment. These response rates were consistently maintained at second follow-up after a median of 22 months. Ten patients (83%) reported adverse events (AE), the most common of which were dizziness and fatigue. No cases of drug reactions with eosinophilia and systemic symptoms (DRESS) were observed. The majority of AEs were mild and resolved over time. In addition, most patients were able to reduce their concomitant ASM.DiscussionCenobamate has been shown to be an effective ASM in patients with DRE and in patients with intellectual disabilities. After more than 1 year of treatment with CNB, close monitoring and management of drug–drug interactions may reduce enzyme-inducing ASMs and lead to better long-term outcomes. With CNB treatment, many patients can achieve a reduced overall drug burden while maintaining a reduction in seizures

First epileptic seizure and epilepsies in adulthood. Abridged version ofthe S2k guideline of the German Society for Neurology in cooperationwith the German Society for Epileptology

Holtkamp M, May T, Berkenfeld R, et al. Erster epileptischer Anfall und Epilepsien im Erwachsenenalter. Kurzfassung S2k-Leitlinie der Deutschen Gesellschaft für Neurologie in Zusammenarbeit mit der Deutschen Gesellschaft für Epileptologie. Clinical Epileptology. 2024.The new S2k guideline "First epileptic seizure and epilepsies in adulthood" provides recommendations on clinically relevant issues in five major topics: management of first epileptic seizures, pharmacotherapy, epilepsy surgery, complementary and supportive treatment, and psychosocial aspects. For the topic management of first epileptic seizures, the guideline provides recommendations on identifying the two major differential diagnoses, syncope and psychogenic non-epileptic seizure. The importance of additional examinations such as EEG, MRI and cerebrospinal fluid for syndromic classification and etiological allocation is discussed. Recommendations on neuropsychological and psychiatric screening tests are also given. The topic pharmacotherapy issues recommendations on antiseizure medication in monotherapy for focal, generalized and unclassified epilepsies; patient groups with special challenges such as the aged, women of childbearing potential and people with mental retardation are emphasized. Further issues are indications for measuring serum concentrations of antiseizure medication and possible risks of switching manufacturers. In the topic epilepsy surgery, indications for presurgical assessment and the multiple therapeutic approaches, such as resection, laser ablation, and neurostimulation are presented. Recommendations on postoperative management of patients, including rehabilitation and psychosocial counselling, are given. The topic complementary and supportive therapeutic approaches comprises recommendations on the diagnostics and treatment of common psychiatric comorbidities of epilepsy, such as anxiety disorder, depression and psychosis. Another important issue is the management of psychogenic non-epileptic seizures as a neuropsychiatric differential diagnosis or comorbidity of epileptic seizures. Furthermore, recommendations on the potential role of ketogenic diet and on acupuncture, homeopathy and other complementary approaches are made. The recommendations on psychosocial aspects comprise practical issues, such as fitness to drive a car, training and occupation, medical rehabilitation, sport, transition, patients' self-help, education programs for patients and next of kin, adherence, advise on SUDEP