Higher plasma total tau concentrations among patients reporting CNS-related side effects from antiseizure medication

Background

Side effects from antiseizure medication (ASM) are common in epilepsy but biomarkers for detection and monitoring are missing. This study investigated associations between CNS-related side effects from ASM and blood concentrations of the brain injury markers neurofilament-light (NFL), total tau, glial acidic fibrillary protein (GFAP), S100 calcium-binding protein B (S100B) and neuron-specific enolase (NSE).

Methods

This is a population-based cohort study of adults with epilepsy recruited from five Swedish outpatient neurology clinics from December 2020 to April 2023. Side effects classified as CNS-related: tiredness, dizziness, headache, concentration, memory, mood, motor/tremor, or sleep. Marker concentrations in the groups CNS side effects/no side effects were analyzed with Mann-Whitney U-test and significant differences were included in multivariable logistic regression models adjusting for age, epilepsy duration, seizure status, acquired structural lesion, and mono-/polytherapy.

Results

The cohort consisted of 367 patients, 187 (51 %) were females, the median age was 43 years (IQR 30–61), and 123 (34 %) reported CNS side effects. Total tau was higher among participants reporting CNS side effects (median 4.44 (95 %CI 4.12–4.88) pg/ml) compared with participants without side effects (3.84 (95 %CI 3.52–4.07) pg/ml, p < 0.01). The difference remained significant in multivariable regression models. NSE was higher among participants without side effects but did not remain significant in the multivariable regression model. No differences were observed for NFL, GFAP or S100B.

Conclusions

Higher total tau plasma concentration could be associated with increased risk of CNS side effects from ASM. Longitudinal studies could determine if this reflects vulnerability or detrimental effects of ASM. Trial registration: PREDICT, clinicaltrials.gov identifier NCT04559919.