Cognitive outcome in relation to cerebrospinal fluid markers of neuronal and glial cell damage: A prospective study of tick-borne encephalitis

Objectives Tick-borne encephalitis (TBE) often results in long-term cognitive sequelae. While biomarkers of neuronal and glial injury are established in other neurological conditions, their role in predicting cognitive outcomes in TBE remains unclear. This study investigated whether acute-phase levels of neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and S100B (calcium-binding protein B) in both cerebrospinal fluid (CSF) and serum, and tau and chitinase-3–like protein 1 (YKL-40) in CSF only, were associated with cognitive functioning at follow-up. Methods Ninety-two adults with TBE were recruited in Sweden and Lithuania. CSF and serum samples were collected within 14 days of symptom onset. Neuropsychological testing covering seven cognitive domains was performed six months post-discharge. Raw scores were converted into age- and education-adjusted T-scores; cognitive impairment (CI) was defined as T≤35 on ≥ one test. Group comparisons, correlation analyses, and logistic regressions were conducted, adjusting for age, education, and time-to-testing. ROC analysis evaluated biomarker predictive utility. Results CI was common, particularly affecting verbal working memory and processing speed. Patients with CI were older and had lower education. GFAP and S100B CSF concentrations were significantly higher in the CI group. GFAP, S100B, and tau correlated with poorer performance, especially in psychomotor speed. However, only CSF GFAP remained a significant predictor of CI after adjustment for age, education, and time-to-testing. In ROC analysis, CSF GFAP displayed high specificity (83%) but low sensitivity (35%). Conclusion CSF GFAP showed the strongest association with long-term cognitive outcome and may reflect astrocytic activation related to persistent cognitive impairment.