Recent advances of epilepsy associated with neurofibromatosis type 1

Neurofibromatosis type 1 (NF1) is an autosomal dominant tumor predisposition syndrome caused by pathogenic variants in the NF1 gene. It exhibits highly variable and unpredictable clinical manifestations involving multiple organ systems, with café-au-lait macules and multiple neurofibromas being hallmark features. Epilepsy represents a common central nervous system complication in NF1, though its underlying mechanisms remain poorly understood. NF1 patients with epilepsy exhibit a higher prevalence of developmental delay and learning disabilities. Early identification and personalized therapy are critical for optimal management of this patient population. This review aims to synthesize published literature on the disease, thereby providing a comprehensive, detailed, and updated overview of its entire clinical spectrum.

We conducted a comprehensive literature search in PubMed, China National Knowledge Infrastructure, and Chinese Medical Association Journal Full-text Database for original research articles with available full-text manuscripts in English or Chinese, with a publication cutoff date of March 1, 2025. Our search strategy employed the terms "neurofibromatosis type 1" OR "NF1" combined using the Boolean operator AND with "epilepsy" OR "seizure." Priority was given to studies published in the last decade, though seminal earlier research was also incorporated.

An extensive bibliography was researched and summarized in the review. Epilepsy represents a common central nervous system complication in NF1, though its underlying mechanisms remain poorly understood. NF1-associated epilepsy demonstrates diverse seizure semiologies, with focal seizures being the most prevalent phenotype. Although the majority of patients demonstrate favorable responses to oral anti-seizure medications, those with structural brain abnormalities frequently develop drug-resistant epilepsy. Notably, a subset of these patients may achieve significant seizure reduction or complete remission through surgical intervention when the epileptogenic zone is clearly delineated. Furthermore, while targeted therapies remain an active area of investigation, their application in NF1-associated epilepsy remains supported only by case report-level evidence.

This review comprehensively summarizes current knowledge regarding the pathogenesis, clinical characteristics, diagnostic approaches, and therapeutic strategies for NF1-related epilepsy, aiming to optimize diagnostic accuracy and treatment outcomes for affected individuals.