Association between pro-inflammatory proteins and neurofilament in plasma from persons with epilepsy.

Background: Inflammation and neurodegeneration are emerging as pathophysiological processes of interest in epilepsy. Seizures can both arise from and induce inflammation and difficult-to-treat epilepsy is linked to brain atrophy. However, the interplay between inflammation and neurodegeneration remains poorly understood in epilepsy. This study investigates the association between inflammatory proteins and plasma neurofilament light chain (NEFL or NfL), a known marker of neurodegeneration, particularly in relation to active epilepsy.

Methods: We performed Olink proteomics on plasma from 176 epilepsy patients aged between 18 and 50 years. To assess systemic inflammation, a composite pro-inflammatory score was derived from the expression of 12 pro-inflammatory proteins. Patients were stratified based on pro-inflammatory score and NEFL and correlation between them was analyzed. Seizure frequency and drug resistance were assessed across patient subgroups.

Results: Pro-inflammatory score and NEFL showed weak positive correlation (r = 0.1); not all patients with high levels of inflammation had high levels of NEFL. In the small proportion of patients (11%, n = 19) with high inflammation and elevated NEFL, seizures (Kruskal-Wallis test H = 9.68, p = 0.02) and drug-resistant epilepsy (χ² = 13.47, p = 0.036, df = 6) were more common, whereas patients with low inflammation and normal NEFL (31.8%, n = 56) tended to have well-controlled epilepsy. Moreover, patients with high inflammation and abnormal NEFL showed protein changes suggestive of potential blood-brain barrier disruption and leukocyte migration.

Conclusions: Inflammation and neurodegeneration are not necessarily linked in all epilepsy patients, but both are more likely to exist in the subset of cases with many seizures. Conversely, absence of both processes indicates well-controlled epilepsy. The combination of plasma NEFL with inflammatory markers could improve seizure prediction and provide novel insights for personalized epilepsy management.