Early Use of Cenobamate in a Case of Non-Convulsive Status Epilepticus in a Woman with Progressive Multifocal Leukoencephalopathy

Presenter: E. Gentile

This case report describes the early use of cenobamate (CNB) in a patient with non-convulsive status epilepticus (NCSE) that did not respond to multiple antiseizure medications. NCSE is a form of status epilepticus (SE) without prominent motor symptoms, and the use of anaesthetic therapy may not be appropriate in patients who remain conscious. A 54-year-old woman with multiple sclerosis had previously received natalizumab before being diagnosed with progressive multifocal leukoencephalopathy. One year later, she was admitted with acute aphasia, right head deviation, and impaired consciousness (Glasgow Coma Scale score of 10). Magnetic resonance imaging (MRI) showed hyperintensities and oedema in the right hemisphere, while electroencephalography (EEG) confirmed right focal status epilepticus with contralateral motor signs that was resistant to benzodiazepines, levetiracetam, and lacosamide. After a few days, the condition evolved into NCSE with preserved consciousness, repetitive right head deviation, inability to walk, and a modified Rankin Scale score of 5. The addition of perampanel (8 mg/day) as a third antiseizure medication did not result in electroclinical improvement. Cenobamate was then introduced and gradually increased to 200 mg/day over one month, after which clinical and electroencephalographic improvement was observed. Follow-up MRI showed resolution of the peri-ictal changes in the right hemisphere, and a 2-month follow-up EEG confirmed that there was no relapse of NCSE.

In conclusion, current evidence for cenobamate in NCSE is limited to anecdotal reports. Although its slow dose titration is a limitation, it may be considered as a third-line treatment in selected patients with subtle clinical manifestations. In addition, CNB may help in regulating dysfunction in GABA seen in NCSE.

A Retrospective Cohort Study of Valproate and Infertility in Men with Epilepsy or Bipolar Disorder Using International Health Data

Presenter: G. Mbizvo

This retrospective cohort study evaluated whether valproate use is associated with infertility in men with epilepsy or bipolar disorder. The analysis used data from the TriNetX international healthcare network and included men aged younger than 55 years. Three cohorts were evaluated: men with epilepsy or bipolar disorder, epilepsy alone, and bipolar disorder alone. Patients exposed to valproate were compared with those who were not exposed. Follow-up began after the second valproate prescription in the exposed group or after the second disease diagnosis in the unexposed group. More than 140 baseline characteristics were balanced using propensity score matching. Among 627,720 men with epilepsy or bipolar disorder, 91,917 had been exposed to valproate and 535,803 had not. Detectable serum valproate levels were reported in 98% of tested exposed patients. After propensity score matching, 78,971 men were included in each group. There were no significant differences in infertility outcomes between men exposed and unexposed to valproate. The hazard ratio for male infertility was 1.057 (95% confidence interval [CI], 0.864–1.295). The hazard ratios were 0.916 (95% CI, 0.824–1.019) for testicular hypofunction, 1.000 (95% CI, 0.682–1.465) for testicular atrophy, and 0.856 (95% CI, 0.613–1.196) for the composite outcome of low sperm concentration, motility, vitality, normal forms, or semen volume. Although total testosterone levels were modestly lower in men exposed to valproate, they remained within the normal range. No differences were observed for other hormone levels. Similar findings were reported when the analyses were performed separately for epilepsy and bipolar disorder.

Overall, the study found no evidence of an association between valproate use and infertility in men with epilepsy or bipolar disorder in a real-world setting.

A Systematic Review of Lamotrigine Overdose: From Uneventful to ICU Admission and Cardiac Arrest

Presenter: L. Taruffi

Lamotrigine (LTG) is a drug which is widely used for treating epilepsy and depression. This systematic review evaluated the clinical features and outcomes of lamotrigine overdose and also included an original case report. A PubMed search identified 40 studies, with an additional 7 studies found through reference screening, resulting in 47 patients being included in the analysis. Data collected included patient characteristics, indication for lamotrigine use, reason for overdose, complications, electroencephalography (EEG) findings, and clinical outcomes. Among the 47 patients, 27 were female, and the mean age was 28.3 years. Nineteen patients had taken other substances in addition to lamotrigine. The most common reason for overdose was suicidal intent (33 cases). Lamotrigine had been prescribed mainly for bipolar disorder (55%) and epilepsy (28%). Seizures occurred in 45% of overdose cases, including 5 single seizures, 10 seizure clusters, and 11 cases of status epilepticus. Among the 13 patients with epilepsy, 6 experienced seizures following overdose. The median ingested dose was 4.7 g (interquartile range [IQR], 2.7–9.5 g), and the median plasma lamotrigine concentration was 35.75 mg/L (IQR, 25.3–52.8 mg/L). Serious complications were common. Three patients (6%) died, 5 (11%) experienced cardiac arrest, and 25 patients required admission to the intensive care unit (ICU). EEG findings were available for 23 patients: 3 had ongoing seizures, 12 showed slowing or epileptiform abnormalities, and the remaining EEGs were unremarkable. A 75-year-old man with temporal lobe epilepsy, developed tonic-clonic status epilepticus after mistakenly taking an excessive dose of lamotrigine. His plasma lamotrigine concentration was 39.73 mg/L, and he required prolonged ICU care followed by rehabilitation.

Overall, the review found that lamotrigine overdose can lead to severe neurological complications, including coma, status epilepticus, cardiac arrest, and death. While suicidal intent was the most common cause of overdose, accidental overdoses also occurred in children and older adults.

Does Time Since Diagnosis or the Number of Failed ASMs Matter More in People with DRE Receiving VNS Therapy?

Presenter: M. Boffini

This study evaluated whether the time since diagnosis of drug-resistant epilepsy (DRE) and the number of failed antiseizure medications (ASMs) influence outcomes after vagus nerve stimulation (VNS) Therapy. Data were obtained from participants enrolled in the Clinical Outcomes Registry for the vagus nerve stimulation (CORE-VNS) study who had not previously received VNS Therapy. Participants were grouped according to the time from DRE diagnosis to VNS implantation: early intervention (<5 years), intermediate intervention (5 to <10 years), and late intervention (≥10 years). They were also categorized based on the number of failed ASMs: 2–3, 4–6, 7–10, 11–16, or more than 16. Outcomes, including seizure frequency and quality of life, were assessed at 3, 6, 12, 24, and 36 months. At 36 months, patients who received VNS Therapy within 5 years of diagnosis showed greater reductions in seizure frequency than those treated after 10 years or more. The median reduction in seizure frequency was 88.2% (95% confidence interval [CI], 76.5%–100%) in the early intervention group compared with 71.4% (95% CI, 55.0%–81.6%) in the late intervention group. Complete seizure freedom (100% reduction in seizure frequency) was achieved by 40.2% of patients in the early intervention group, compared with 22.6% in the late intervention group. Patients who had failed fewer ASMs before VNS implantation were also more likely to respond to treatment than those who had failed a larger number of ASMs, even after adjusting for factors including age and time since diagnosis (p < 0.05). At 36 months, patients who received VNS Therapy after failing 2–3 ASMs had a 94.4% median reduction in seizure frequency, compared with a 57.4% reduction in those who had failed 11–16 ASMs.

"The findings suggest that delayed implantation and repeated ASM trials may reduce the benefits associated with early VNS Therapy."

First Antiseizure Medication Choice in Older Adults with Seizures: An Observational Cohort Study Based on a Claims Database

Presenter: P. Vassallo

This nationwide, claims-based study evaluated first-line antiseizure medication (ASM) prescribing patterns in adults aged 50 years and older with newly diagnosed epilepsy, with a focus on sex differences, cardiovascular risk profiles, and the use of enzyme-modulating ASMs. Data were obtained from the Dutch Vektis health insurance database and included patients diagnosed with seizures in 2014. 

"Analyses were restricted to patients with incident seizures who received a single ASM after diagnosis."

Among 8,728 adults with incident seizures, 3,583 received a single ASM following diagnosis. Of these, 42.5% (1,524) were women, and the median age was 70 years (range, 60–102 years). Levetiracetam (53%) and valproic acid (30%) were the most commonly prescribed first-line ASMs in both men and women. Enzyme-modulating ASMs continued to be prescribed frequently, including in patients receiving cardiovascular medications. Carbamazepine was prescribed more often in women, while lamotrigine was the fifth most commonly prescribed ASM overall. Men had longer prescription intervals than women. Prescribed daily doses were similar between sexes but were lower in patients older than 70 years. No significant association was found between the use of enzyme-modulating ASMs and the time to initiation of lipid-lowering therapy.

Overall, the study showed that older ASMs remain commonly used in routine clinical practice despite cardiovascular co-medication. Differences in prescribing patterns were observed by sex and age, which may help inform treatment decisions for specific patient groups.

Efficacy and Adverse Event Profile of Pharmacological and Non-Pharmacological Therapies in Dravet Syndrome: A Systematic Review

Presenter: C. Michel

This systematic literature review evaluated treatment-related complications in patients with Dravet syndrome (DS), a severe epileptic encephalopathy that requires long-term pharmacological treatment, which includes cognitive, behavioural, and systemic complications. The review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Of 74 identified studies, 7 met the inclusion criteria. The review assessed treatment regimens, clinical outcomes, and treatment-related adverse effects. A total of 275 patients with Dravet syndrome were included, with a mean age of 14.3 years. The most commonly used treatments were fenfluramine, valproate, clobazam, and stiripentol. Additional therapies included cannabidiol/tetrahydrocannabinol (THC) in 19 patients and the ketogenic diet in 60 patients. Across the included studies, 58–83% of patients achieved at least a 50% reduction in seizure frequency, while 7.6–25% became seizure-free. Adverse effects were common but were generally manageable. Somnolence was the most frequently reported adverse effect, occurring in up to 59.1% of patients, while the overall rate of adverse events was up to 31.5%. Treatment discontinuation due to adverse effects occurred in less than 21% of cases.

Overall, the available evidence suggests that fenfluramine and the ketogenic diet can reduce seizure frequency in patients with Dravet syndrome, although complete seizure freedom was achieved in only a minority of patients. Responses to cannabinoid-based therapies were variable. The differences in study design, co-interventions, and incomplete reporting of safety outcomes limited comparisons across studies and highlighted the need for standardized studies with systematic adverse event monitoring.

Cenobamate for Refractory Epilepsy Secondary to Primary CNS Tumours: Real-World Outcomes Across WHO Classifications

Presenter: M. Elbadri

Epilepsy is the most common long-term neurological condition in patients with primary central nervous system (CNS) tumours. Cenobamate (CNB), a third-generation antiseizure medication (ASM), works well for focal epilepsy, but evidence for brain tumour-related epilepsy (BTRE) remains limited. This real-world observational study evaluated the effectiveness and tolerability of cenobamate in patients with BTRE. The study included patients treated with cenobamate at the Queen Elizabeth Hospital Birmingham between 2022 and 2025. Brain tumours were classified according to the 2021 World Health Organization (WHO) Central Nervous System tumour classification. Data collected included tumour type and grade, baseline seizure frequency, adverse events, and changes in antiseizure medication (ASM) use. A total of 25 patients with World Health Organization grade I–IV brain tumours were included, with a median follow-up of 19 months. The mean number of concomitant ASMs decreased from 2.75 at baseline to 1.79 after starting cenobamate. Overall, 11 of 25 patients (44%) achieved at least a 50% reduction in seizure frequency, while 6 patients (24%) achieved at least a 90% reduction. Treatment responses were observed across different tumour subtypes and tumour grades. Cenobamate was generally well tolerated. Three patients (12%) discontinued treatment because of adverse effects, with somnolence and sedation being the most commonly reported reasons for discontinuation.

Overall, this large real-world study suggests that cenobamate was associated with clinically meaningful seizure reduction in 40% patients with refractory brain tumour-related epilepsy and showed a generally favourable tolerability profile across different tumour types.

Cenobamate in Brain Tumor-Related Epilepsy: A Multicenter Real-World Experience

Presenter: M. Romozzi

Brain tumor–related epilepsy (BTRE) is a serious complication seen in brain tumors. It remains uncontrolled following antiseizure medications (ASMs). This multicenter retrospective observational study evaluated the effectiveness and safety of cenobamate (CNB) as add-on therapy in adults with drug-resistant brain tumor-related epilepsy (BTRE). The study was conducted across tertiary epilepsy centers in Italy and assessed changes in monthly seizure frequency, responder rates, and safety using an intention-to-treat (ITT) analysis. A total of 20 patients were included, including 10 women, with a median age of 48 years. Tumor types included meningioma (35%), astrocytoma (20%), glioblastoma (15%), ganglioglioma (15%), oligodendroglioma (10%), and dysembryoplastic neuroepithelial tumour (DNET) (5%). The median follow-up was 12 months (interquartile range [IQR], 9.8–12 months). In the ITT population, the median monthly seizure frequency decreased significantly from 6 seizures (IQR, 18.75) at baseline to 1 seizure (IQR, 2.55) at the last follow-up (p = 0.006). The median seizure reduction was 49.7%. Overall, 50% of patients achieved at least a 50% reduction in seizure frequency, 30% achieved at least a 75% reduction, and 20% became seizure-free. One patient discontinued treatment before the 3-month follow-up, and one patient with glioblastoma died before the 6-month follow-up. Reported adverse events were predominantly mild to moderate in severity.

Overall, add-on cenobamate therapy was associated with a substantial reduction in seizure frequency and was generally well tolerated in patients with drug-resistant brain tumor-related epilepsy.

EAN 2026, June 27-30, Geneva, Switzerland