Peculiarities of the Course of Epilepsy in Neurofibromatosis Type 1

Abstract

Neurofibromatosis type 1 is an inherited neurocutaneous disorder occurring with an incidence of 1 in 2,000–4,000 newborns. Epilepsy is one of its neurological manifestations; however, data on its frequency, pathogenesis, and treatment approaches have not been fully elucidated. Aim: to summarize current data on the pathogenesis, clinical features, diagnosis and treatment of epilepsy in type I neurofibromatosis based on literature analysis and the results of our own prospective patient observation. This article presents an analysis of current literature on epilepsy in neurofibromatosis type 1, including data on molecular mechanisms (the «second hit», hyperactivation of the Ras/Raf/MAPK and PI3K-mTOR pathways). In addition, we present the results of a prospective observational study of 724 patients with neurofibromatosis type 1 (aged 1 to 19 years) from 2021 to 2026. According to the literature, the prevalence of epilepsy in neurofibromatosis type 1 ranges from 4% to 14%. Focal seizures predominate (up to 83%). In our own cohort (n=724), epileptiform activity was recorded in 34 patients (4.7%), and epilepsy was diagnosed in 28 of these (82.4% of those with epileptiform activity). Among patients with epilepsy (n=28), focal seizures prevailed (82.1%), while structural changes on magnetic resonance imaging (MRI) were identified in only 14.3% of cases, which is consistent with international data. Remission was achieved in 67.9% of patients. The article also presents a clinical case of a 14-year-old patient with neurofibromatosis type 1, plexiform neurofibromas, and photosensitive focal epilepsy. Epilepsy in neurofibromatosis type 1 is relatively uncommon, but establishing the diagnosis and determining treatment strategies requires mandatory additional investigations, including MRI and video-EEG monitoring. The pathogenesis involves a combination of structural changes (gliomas, cortical dysplasias, hippocampal sclerosis) and molecular neuronal dysfunction resulting from hyperactivation of the Ras-MAPK and PI3K-mTOR pathways. The prognosis is generally favourable, and clinical remission can be achieved in most cases. Surgical treatment options should be considered in drug resistant forms of epilepsy. Patients with negative MRI findings are potential candidates for pathogenetic therapy with MEK inhibitors.