Felix Rosenow

Background: To address the paucity of data on outcomes and costs of status epilepticus (SE) following the updated 2015 International League Against Epilepsy (ILAE) definition and changes in clinical practice guidelines in Germany. Methods: This prospective population‐based study (October 2018–March 2020) included adult patients from postal code area prefix 35, representative of Germany, diagnosed with SE according to the 2015 ILAE definition. Costs were calculated using German Diagnosis‐Related Groups (G‐DRG). Results: In total, 181 patients were included. Mean inpatient costs were €10,543 (median €6376; range €845–€133,267), corresponding to €939 per hospital day (median €580.8; range €76.8–€12,115). Mean length of stay (LOS) was 11 days (median 9; range 1–67). In univariable analyses, super‐refractory SE was associated with higher costs and longer LOS (both p < 0.001), while acute symptomatic etiology was associated with longer LOS ( p = 0.006). On multivariable analysis, mechanical ventilation was the strongest independent predictor of costs (Exp(B) = 2.918, 95% CI 1.753–4.857; p < 0.001), and etiology was overall significantly associated with cost variation ( p = 0.022), with acute symptomatic SE showing the highest adjusted costs. Discharge destination correlated with SE severity, with most patients with non‐refractory SE discharged home ( p = 0.028). Conclusions: This study provides population‐based data on costs and outcomes of SE in Germany, serving as a basis for future cost‐effectiveness analyses. Compared with earlier studies, lower direct costs and shorter LOS were observed. Identification of high‐risk constellations may support clinical decision‐making and optimize monitoring, treatment escalation, and allocation of intensive care resources.

Objective: The polygenic risk score (PRS) for individuals with genetic generalized epilepsy (GGE) quantifies the common risk variants in genes identified in genome‐wide association studies. We hypothesized that the phenotype of GGE patients differs based on their GGE PRS. Methods: We identified participants with highest ( n = 59) versus lowest ( n = 48) PRS from the GGE patients ( n = 2256) recruited through the Epi25 Collaborative for comparison. Detailed clinical data were acquired retrospectively for the 59 high PRS and 48 low PRS individuals with GGE from the Epi25 database and from the contributing centers. For validation, we accessed a larger cohort ( n = 1175) of patients with GGE included in the Epi25 Collaborative. Results: This study found no difference in phenotypic features of patients between the high‐PRS GGE and low‐PRS GGE subgroups, including age at onset, family history, and specific GGE syndrome. However, more patients from the lowest compared to the highest PRS subgroup were pharmacoresistant (31.7% vs. 8.9%, p = .01). On validation in a larger cohort, the PRS did not differ in the group of pharmacoresistant compared to nonpharmacoresistant patients. Significance: No meaningful association between PRS and age at onset, history of febrile seizures, pre‐/perinatal complications, epilepsy syndromes, seizure types, co‐occurrence of functional/dissociative (nonepileptic) seizures, psychiatric comorbidities, electroencephalographic/magnetic resonance imaging findings, or drug response could be demonstrated in this study of people with GGE.

Objective: Despite decades of research, the circuit mechanisms that underlie focal epileptogenesis remain incompletely understood. In this study, we aimed to characterize the changes in hippocampal network activity induced by an epileptogenic insult. Methods: In rats, prolonged electrical perforant pathway stimulation leads in a high percentage of animals to the development of temporal lobe epilepsy. However, a subset of animals remained apparently non‐epileptic for unknown reasons. We monitored alterations of neuronal activity by chronically recording the local field potential (LFP) from the hippocampal dentate gyrus before, during, and after the potentially epileptogenic insult and quantifying the time‐dependent changes in the periodic and the aperiodic components of the LFP. Results: It is intriguing that animals with epilepsy identified by subsequent spontaneous epileptic seizures were characterized by a transient increase in the aperiodic exponent, suggesting a shift toward a reduced local excitation‐to‐inhibition (E/I) ratio during the first days after the perforant path stimulation. Furthermore, these animals developed a strong impairment of theta oscillation prevalence and regularity during early epileptogenesis. In contrast, resilient non‐epilepsy animals without spontaneous seizures showed neither this modulation in E/I ratio nor a corruption of hippocampal theta activity. In fact, the increase in the aperiodic exponent on the first day after completion of the electrical stimulation paradigm could predict epileptogenesis with very high fidelity (area under the curve [AUC] 0.92) and correlated significantly with later seizure rate. Significance: The very early phase of epileptogenesis seems to be dominated by a relative dominance of inhibitory synaptic activity in affected circuits. This finding opens the opportunity to dissect mechanisms of epileptogenesis and to test the effectiveness of anti‐epileptogenesis treatment in very early disease stages by allowing identification of individuals at high risk. Furthermore, it might offer a potential explanation for the frequently observed failure of anti‐epileptogenesis drugs boosting γ‐aminobutyric acid (GABA)ergic inhibition.

Objective: Epilepsy affects ~1% of the global population and often requires lifelong antiseizure medication (ASM) therapy. Valproic acid (VPA) is a commonly prescribed first‐line ASM, yet only approximately half of patients achieve sustained seizure freedom. Treatment selection remains largely empirical. We aimed to develop and independently validate a multimodal predictive model to estimate response to VPA and support more individualized treatment strategies. Methods: This cross‐sectional treatment response modeling study used data from a subset of the international Epi25 cohort (Belgium, Finland, Germany). Individuals with epilepsy were included if they had received VPA monotherapy and had available genetic or clinical data. Discovery data (1965–2021, 58% female) were split into a training set ( n = 196) and test set ( n = 133). Independent validation was performed in a Canadian cohort (2021–2022, n = 156, 40% female). The primary outcome was binary VPA response. Responders achieved ≥12 months of seizure freedom attributed to VPA; nonresponders had >50% seizure recurrence or discontinued VPA due to inefficacy, adverse effects, or unclear reasons. The predictive algorithm integrated features derived from common and rare variants in VPA pharmacokinetic and pharmacodynamic genes, in vitro neuronal VPA response measures, and clinical features. Model performance was assessed using accuracy, predictive values (negative predictive value [NPV]/positive predictive value [PPV]), and area under the curve (AUC). Results: In the independent validation cohort, the multimodal classifier achieved a balanced accuracy of 63% (95% confidence interval [CI] = 52%–73%), NPV of 70% (95% CI = 51%–85%), PPV of 60% (95% CI = 46%–72%), and AUC of .73 (95% CI = .63–.83). Models restricted to single or dual data modalities showed consistently lower predictive performance. Significance: This proof‐of‐concept study demonstrates that integrating genetic, cellular, and clinical data enables prediction of VPA treatment response with clinically meaningful accuracy. Although not yet ready for clinical application, this approach supports the feasibility of biomarker‐informed ASM selection and may ultimately reduce time to effective seizure control.

Objective: To synthesize adverse event (AE) data from randomized controlled trials (RCTs) of levetiracetam (LEV) and brivaracetam (BRV), compare their safety profiles, and identify moderators of AE risk. Methods: We conducted a systematic review and meta-analysis of RCTs of LEV or BRV, searching PubMed, Web of Science, and ClinicalTrials.gov to August 2025. AE frequencies were summarized qualitatively, and random-effects meta-analyses compared LEV and BRV with placebo. Additional analyses compared LEV and BRV and assessed moderators. PROSPERO: CRD42023491050, CRD420251003207. Results: Ninety-six RCTs including 7145 patients exposed to LEV and 2549 to BRV were analyzed. Qualitative synthesis identified headache, somnolence, dizziness, and fatigue as the most common AEs, with higher frequencies of some psychiatric AEs (e.g., irritability, aggression) reported for LEV. Meta-analyses showed increased somnolence with both LEV (OR 1.80, 95% CI [1.41–2.30]) and BRV (OR 1.86, 95% CI [1.33–2.61]). LEV was additionally associated with irritability (OR 2.55, 95% CI [1.41–4.63]) and asthenia (OR 1.71, 95% CI [1.15–2.54]), whereas BRV was associated with dizziness (OR 1.75, 95% CI [1.24–2.46]) and fatigue (OR 2.14, 95% CI [1.43–3.20]). Few moderators of AE risk were identified, and no significant differences emerged between LEV and BRV in indirect comparisons. Conclusion: LEV and BRV show favorable safety profiles that appear comparable based on meta-analytic findings, despite higher rates of some psychiatric AEs with LEV on a descriptive level. Both remain safe treatment options, though larger head-to-head trials are needed to provide definitive comparative evidence.

The circuit mechanisms underlying focal epileptogenesis are, despite of decades of epilepsy research, still incompletely understood. In this study, we aimed to characterize the changes in hippocampal network activity induced by a potentially epileptogenic insult. In rats, long-lasting electrical perforant pathway stimulation leads in a high percentage of animals to the development of temporal lobe epilepsy. However, a subset of animals remains resilient against the stimulation. We monitored alterations of neuronal activity by chronically recording the local field potential (LFP) from the hippocampal dentate gyrus before, during and after the potentially epileptogenic insult. Intriguingly, epilepsy animals identified by subsequent spontaneous epileptic seizures were characterized by a transient increase in the aperiodic exponent suggesting a shift towards a reduced local excitation-to-inhibition (E/I) ratio during the first days after the perforant path stimulation. Furthermore, these animals developed a strong impairment of theta oscillation prevalence and regularity during early epileptogenesis. In contrast, resilient non-epilepsy animals without spontaneous seizures neither showed this modulation in E/I ratio nor a corruption of hippocampal theta activity. In fact, the increase in the aperiodic exponent on the first day after completion of the electrical stimulation paradigm could predict epileptogenesis with very high fidelity (AUC 0.92) and correlated significantly with later seizure rate. This finding opens the opportunity to dissect mechanisms of epileptogenesis and to test the effectiveness of anti-epileptogenesis treatment in very early disease stages by allowing identification of individuals at high risk. Furthermore, it might offer a potential explanation for the frequently observed failure of anti-epileptogenesis drugs boosting GABAergic inhibition.