Diagnostic and prognostic value of blood neurofilament light

Authors

Lorenzo Barba, Michele Romoli, Pascal Benkert, Lisa Hofer, Luis F Maia, Alexandre Dias, Rui Magalhães, Catarina Guedes Vaz, Jan Emmerich, Kristian Barlinn, Christoph Vollmuth, Hermann Neugebauer, Marta Truffi, Carlo Morasso, Federica Ferrari, Grant O'Connell, Steffen Tiedt, Dilara Moumin, Thomas Gattringer, Markus Kneihsl, Michael Khalil, Annie Pedersen, Tara M Stanne, Sofia Furutjäll, Christina Jern, Helle H Nielsen, Kate L Lambertsen, Mi-Yeon Eun, June Woo Ahn, Poosanu Thanapornsangsuth, Wanakorn Rattanawong, Fani Pujol-Calderón, Henrik Zetterberg, Kaj Blennow, Marianne Hahn, Timo Uphaus, Klaus Gröschel, Valentina Tudisco, Julian Klingbeil, Arthur Guthknecht, Samir Abu-Rumeileh, Simona Sacco, Matteo Foschi, Lucio D'Anna, Jens Kuhle, Markus Otto, Valeria Caso

Abstract

J Neurol. 2026 May 16;273(6):316. doi: 10.1007/s00415-026-13849-3.

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participants (IS n = 1985, transient ischemic attack n = 88, healthy controls n = 799) of 18 published studies and 3 unpublished cohorts.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.

PMID:42142116 | DOI:10.1007/s00415-026-13849-3