Elevated plasma neurofilament light & glial fibrillary acidic protein in epilepsy versus non-epileptic seizures & non-epileptic disorders

BackgroundResearch suggests that recurrent seizures may lead to neuronal injury. Neurofilament light chain protein (NfL) and glial fibrillary acidic protein (GFAP) levels increase in cerebrospinal fluid and blood following neuroaxonal damage, and have been hypothesised as potential biomarkers for epilepsy. We examined plasma NfL and GFAP levels and their diagnostic utility in differentiating patients with epilepsy from those with psychogenic non-epileptic seizures (PNES), and other non-epileptic disorders. MethodsWe recruited consecutive adults admitted for video-electroencephalography monitoring and formal neuropsychiatric assessment. Plasma samples were collected on admission. NfL and GFAP levels were quantified and compared between patient groups and an age-matched reference cohort (n=1,926), and correlated with clinical variables. Results149 patients were included. 115 were diagnosed with epilepsy, 22 with PNES and 12 with other conditions. Plasma NfL and GFAP levels were elevated in patients with epilepsy compared to PNES, adjusted for age and sex (NfL p=0.004, GFAP p=0.004). A significantly higher proportion of patients with epilepsy (26%) had NfL levels above the 95th age-matched percentile compared to the reference cohort (5%; p=0.0265). NfL levels above the 95th percentile of the reference cohort had a 97% positive predictive value for epilepsy. DiscussionElevated NfL or GFAP levels may support an underlying epilepsy diagnosis and caution against a diagnosis of PNES alone. Further examination of associations between NfL and GFAP levels and specific epilepsy subtypes or seizure characteristics may provide valuable insights into disease heterogeneity and contribute to the refinement of diagnosis, understanding pathophysiological mechanisms, and formulating treatment approaches.