Higher plasma neurofilament-light chain concentration in drug-resistant epilepsy

Drug-resistant epilepsy is the most severe form of epilepsy and is frequently associated with cognitive decline. Whether drug-resistant epilepsy results in neurodegeneration or other types of brain injury is not known, and early detection of detrimental clinical trajectories would be clinically very useful. Blood biomarkers of brain injury reflect neurodegeneration or brain injury in several brain diseases but have not been extensively studied in epilepsy. We investigated a panel of such markers in a large epilepsy cohort with an emphasis on assessing differences between drug-resistant and monotherapy-controlled epilepsy. Blood neurofilament light, glial fibrillary acidic protein, total tau, S100 calcium-binding protein B and neuron-specific enolase concentrations were measured in 444 patients (aged ≥ 18 years) with epilepsy participating in a prospective regional Biobank study in Västra Götaland (Sweden). Multiple linear regression assessed associations between clinical variables and marker levels. Levels were then compared between patients with drug-resistant epilepsy (n = 101) and patients with monotherapy-controlled epilepsy (n = 164). We also performed logistic regression analysis to evaluate the significance of the markers as predictors of epilepsy status (drug-resistant epilepsy or monotherapy-controlled epilepsy) while controlling for clinical variables: age, sex, epilepsy duration, epilepsy type and lesions. All markers correlated with age. In younger patients (≤50 years), cases of drug-resistant epilepsy had higher levels of neurofilament light (P = 0.002) and glial fibrillary acidic protein (P = 0.006) compared with monotherapy-controlled epilepsy. After excluding patients with known structural lesions, neurofilament light levels remained significantly elevated in drug-resistant epilepsy versus monotherapy-controlled epilepsy (P = 0.029). Neurofilament light also emerged as a significant predictor of drug-resistant status in a logistic regression model following adjustments for clinical variables. Future studies should explore if neurofilament light can be used for surveillance of disease course and whether it reflects brain injury in drug-resistant epilepsy.