Epilepsy in paediatric neurofibromatosis type 1: clinical features and associated factors in a single-centere cohort

Neurofibromatosis type 1 (NF1) is associated with an increased risk of epilepsy, but the clinical spectrum and associated factors of epilepsy in paediatric NF1 remain incompletely characterized. We aimed to describe frequency and features of epilepsy in paediatric NF1 and to compare the characteristics of NF1 patients with and without epilepsy. We retrospectively reviewed 253 paediatric NF1 patients followed up between January 2020 and December 2025. Demographic, clinical, electroencephalographic, and radiological data were collected. Categorical comparisons between patients with and without epilepsy were performed using χ2 or Fisher's exact tests. Of 253 patients (53.8% female; median age 12.3 years), 12 (4.74%) had epilepsy. Median age at epilepsy onset was 3.2 years (IQR 2.4-7.0). Seizure semiology was focal in 7 (58.3%) and generalized in 5 (41.7%). EEG reports were available in 10 patients: normal in 4, focal discharges in 4, and multifocal discharges in 2; no patient had generalized spike-and-wave discharges. Four (33.3%) had drug-resistant epilepsy; median number of antiseizure medications was 1, median seizure-free duration was 44 months. Compared with patients without epilepsy, those with epilepsy had significantly higher rates of moyamoya syndrome (25.0% vs 0.4%, p < 0.001), autism spectrum disorder (16.7% vs 0%, p = 0.002), learning difficulties (58.3% vs 14.5%, p < 0.001), and overall neurodevelopmental comorbidity (83.3% vs 29.0%, p < 0.001). No significant differences were found in the frequencies of neurofibromatosis bright objects (NBOs), optic pathway gliomas, or low-grade gliomas.

In our cohort, epilepsy occurred in 4.74% of patients. Most had favorable seizure outcomes. Epilepsy was associated with cerebrovascular anomalies and neurodevelopmental comorbidities but not with NBOs or intracranial tumours. These findings suggest that children with NF1 and cerebrovascular abnormalities may warrant particular vigilance for seizures, while those with epilepsy should undergo systematic neurodevelopmental assessment.

• Epilepsy affects 4-14% of patients with NF1, is usually mild, but its determinants remain poorly defined. • Neurofibromatosis bright objects show no consistent association with epilepsy.

• In 253 children, epilepsy (4.74%) was associated with moyamoya syndrome and neurodevelopmental comorbidity. • Optic pathway gliomas, low-grade gliomas and bright objects did not predict epilepsy.