NfL and GFAP are elevated in MRI-negative TIA, supporting the presence of transient microscopic brain injury, with combined assessment achieving sensitivity of 80.6% and specificity of 81.9%.
TIA patients with negative MRI showed significantly higher plasma NfL levels compared to healthy controls.
TIA patients with negative MRI showed significantly higher plasma GFAP levels compared to healthy controls.
The optimal diagnostic threshold for NfL showed high specificity but modest sensitivity for distinguishing MRI-negative TIA patients from controls.
The optimal diagnostic threshold for GFAP showed moderate sensitivity and specificity for distinguishing MRI-negative TIA patients from controls.
Combined assessment of NfL and GFAP achieved greater diagnostic accuracy than either biomarker alone.
Elevated NfL and GFAP in TIA patients were confirmed in sensitivity analyses excluding patients with potentially confounding conditions.
The study was a single-center retrospective design using clinically defined, MRI-negative TIA patients.
This research suggests that two proteins measurable in blood — neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) — are elevated in patients who have had a Transient Ischemic Attack (TIA, sometimes called a 'mini-stroke') even when their brain MRI scans appear completely normal. The study compared blood samples from 36 TIA patients, taken within 24 hours of hospital admission, to those of 72 healthy matched individuals. TIA patients had roughly 2.6 times higher NfL levels and about 2.3 times higher GFAP levels than healthy controls, and these differences held up even after accounting for conditions like kidney problems or pre-existing brain changes that can also raise these proteins. The practical implication is that combining both biomarkers could help clinicians identify brain injury in TIA patients that standard MRI misses. When both biomarkers were used together, the test correctly identified about 81% of TIA patients while also correctly ruling out TIA in about 82% of healthy individuals — better performance than either biomarker alone. This research suggests that TIA causes real, albeit microscopic, brain cell damage even when imaging looks normal, and that blood tests might one day help confirm the diagnosis or assess injury severity in these patients. However, this was a small, single-center retrospective study, and the authors note that larger studies are needed to confirm whether these biomarkers have genuine clinical utility. The findings open the door to future research on whether blood biomarkers could complement or reduce reliance on MRI in TIA evaluation.
Berinato F, Morotti A, Baronchelli G, Tolassi C, Girotto I, Pilotto A, et al.. (2026). Blood biomarkers of brain damage in Transient Ischemic Attack: the role of plasma NfL and GFAP.. Journal of neurology. https://doi.org/10.1007/s00415-026-14097-1