Blood biomarkers of brain damage in Transient Ischemic Attack: the role of plasma NfL and GFAP.

OBJECTIVES: Transient Ischemic Attack (TIA) may induce subtle tissue damage that remains undetectable on conventional magnetic resonance imaging (MRI), which has led to growing interest in blood biomarkers of neuronal and glial injury. This study examined whether plasma neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) can distinguish patients with clinically defined, MRI-negative TIA from healthy individuals. METHODS: Single-center retrospective study that included clinical TIA patients with negative MRI. Age- and sex-matched healthy controls were selected. A blood sample was collected within 24 h from admission, and plasma NfL and GFAP were measured using Simoa technology. We performed group comparisons, ROC analyses with identification of optimal thresholds, and evaluation of combined diagnostic assessment. Sensitivity analyses excluding patients with pre-existing disability, previous stroke/TIA, impaired renal function, high MRI small vessel disease burden and moderate-severe cerebral cortical atrophy were performed. RESULTS: 36 TIA patients and 72 controls were analyzed. TIA patients showed higher NfL (27.22 vs 10.44 pg/mL, p<0.001) and GFAP (301.99 vs 131.65 pg/mL, p<0.001) levels. Optimal thresholds were 16.83 pg/mL for NfL (sensitivity 52.8%, specificity 98.6%) and 179.23 pg/mL for GFAP (sensitivity 69.4%, specificity 81.9%). Combined assessment increased sensitivity to 80.6% while maintaining specificity at 81.9% with the highest discriminative accuracy (AUC 0.812). The significantly higher level of NfL and GFAP in TIA patients was confirmed in sensitivity analyses. DISCUSSION: NfL and GFAP are elevated in MRI-negative TIA, supporting the presence of transient microscopic brain injury. Larger studies are needed to confirm clinical utility.