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Diagnostic and prognostic value of blood neurofilament light chain in ischemic stroke: an individual patient data meta-analysis
Author(s)
Barba, Lorenzo
Romoli, Michele
Benkert, Pascal
Hofer, Lisa
Maia, Luis F.
Dias, Alexandre
Magalhães, Rui
Vaz, Catarina Guedes
Emmerich, Jan
Barlinn, Kristian
Vollmuth, Christoph
Neugebauer, Hermann
Truffi, Marta
Morasso, Carlo
Ferrari, Federica
O’Connell, Grant
Tiedt, Steffen
Moumin, Dilara
Gattringer, Thomas
Kneihsl, Markus
Khalil, Michael
Pedersen, Annie
Stanne, Tara M.
Furutjäll, Sofia
Jern, Christina
Nielsen, Helle H.
Lambertsen, Kate L.
Eun, Mi Yeon
Ahn, June Woo
Thanapornsangsuth, Poosanu
Pujol-Calderón, Fani
Zetterberg, Henrik
Blennow, Kaj
Hahn, Marianne
Uphaus, Timo
Gröschel, Klaus
Tudisco, Valentina
Klingbeil, Julian
Guthknecht, Arthur
Abu-Rumeileh, Samir
Sacco, Simona
Foschi, Matteo
D’Anna, Lucio
Kuhle, Jens
Otto, Markus
Caso, Valeria
Date Issued
June 1, 2026
Type
Article
Abstract
Background: We aimed to conduct an individual patient data meta-analysis on blood neurofilament light chain (NfL) in ischemic stroke (IS) to enhance its clinical applicability. Methods: We performed a systematic literature search of studies on blood NfL measured in adult patients within 30 days after IS onset and derived age- and BMI-adjusted Z-scores based on a previously published reference population of healthy controls. We collected clinical, radiological and biochemical parameters of IS patients and tested associations of NfL at defined timepoints after IS onset (D1: < 24 h; D2: 24–48 h; D3: 48–72 h; D4–5: 72–120 h; D6–7: 120–168 h; D8–30: > 168 h) with baseline characteristics and 3-month follow-up outcomes (modified Rankin Scale, mRS; survival). Results: We included 4081 blood NfL values from 2872 participants (IS n = 1985, transient ischemic attack n = 88, healthy controls n = 799) of 18 published studies and 3 unpublished cohorts. In patients with IS, NfL Z-score progressively increased from D1 [median: 2.0 (IQR: 0.9–2.9)] to D6–7 [median: 3.5 (IQR: 3.0–3.8)], with discriminative ability being high for IS vs. controls (AUC: 0.79–0.97) and fair for IS vs. TIA (AUC: 0.64–0.80). Higher NfL Z-score at D1 was associated with greater risk of symptomatic intracranial hemorrhage (aOR = 1.33, p = 0.014) and, from D2 onwards, with larger infarct lesion volume (highest Spearman’s rho: 0.795 at D6-7). NfL independently predicted a mRS > 2 (aOR = 1.31, p < 0.001) and mortality (aOR = 1.67, p < 0.001) at 3 months. Conclusions: Blood NfL level was progressively elevated after IS, could discriminate IS from healthy controls with high accuracy and had prognostic value for intra-hospital complications and 3-month clinical outcomes in IS.
Citation
Journal of Neurology, 273(6), 2026