ABSTRACT NUMBER: ESOC2026A1538 BIOMARKERS OF AXONAL DAMAGE IN ACUTE ISCHEMIC STROKE: ARE NFL, GFAP, AND UCH-L1 PREDICTORS OF LONG-TERM DISABILITY? A SYSTEMATIC REVIEW

Abstract Background and aims Axonal and glial injury are key contributors to long-term disability after acute ischaemic stroke (AIS), yet prognostic models rely mainly on clinical and imaging variables that incompletely reflect microstructural damage. We conducted a systematic review to evaluate the prognostic value of circulating neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) for long-term disability after AIS. Methods Following PRISMA 2020, we searched major databases and trial registries for studies in adults with imaging-confirmed AIS reporting biomarker sampling in serum, plasma or cerebrospinal fluid in the early (≤72 h) or subacute (73 h–14 d) period, and functional outcome at ≥90 days, primarily the modified Rankin Scale (mRS). Risk of bias was assessed using PROBAST. Fourteen studies, predominantly prospective cohorts, were included. Results Higher acute NfL levels correlated with baseline stroke severity and infarct volume and independently predicted unfavourable long-term outcome (mRS >2 or ≥3), with adjusted odds ratios typically 1.3–2.3. In minor stroke, elevated NfL also predicted early neurological deterioration and poorer recovery. GFAP showed similar associations, and models combining GFAP with NIHSS achieved AUC values around 0.8. Evidence for UCH-L1 was limited. Conclusions In conclusion, NfL, and to a lesser extent GFAP, provide independent and incremental prognostic information for long-term disability after AIS. Standardisation of sampling windows, assay methodology and actionable thresholds, alongside multicentre validation, is needed to support personalised post-stroke prognostication and rehabilitation. Conflict of interest Rafael Gomez: Nothing to disclose, Cristopher Miguel: Nothing to disclose, Isaac Medina: Nothing to disclose