Diagnostic and prognostic value of blood neurofilament light chain in ischemic stroke: an individual patient data meta-analysis

Clinical Snapshot

Key Findings

• P Value: p < 0.001 for mRS and mortality prediction, p = 0.014 for ICH prediction

• Effect Size: aOR 1.31 for mRS >2, aOR 1.67 for mortality, aOR 1.33 for symptomatic ICH

• Primary Outcome: Blood NfL Z-score progressively increased from D1 (median 2.0) to D6-7 (median 3.5)

• Nnt Or Sensitivity: AUC 0.79-0.97 for IS vs controls, AUC 0.64-0.80 for IS vs TIA, correlation with infarct volume rho=0.795

• Confidence Interval: Not explicitly reported in abstract

Clinical Application

Requires blood NfL measurement capability, which may not be widely available in all Australian stroke centres Could complement existing stroke assessment protocols in Australian comprehensive stroke centres, potentially informing prognosis discussions and rehabilitation planning, though cost-effectiveness analysis needed for PBS consideration Adult ischemic stroke patients presenting within 30 days of symptom onset

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participants (IS n = 1985, transient ischemic attack n = 88, healthy controls n = 799) of 18 published studies and 3 unpublished cohorts.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

References

1. 1.Barba, L., Romoli, M., Benkert, P., Hofer, L., Maia, L. F., Dias, A., Magalhães, R., Vaz, C. G., Emmerich, J., Barlinn, K., Vollmuth, C., Neugebauer, H., Truffi, M., Morasso, C., Ferrari, F., O'Connell, G., Tiedt, S., Moumin, D., Gattringer, T., Kneihsl, M., Khalil, M., Pedersen, A., Stanne, T. M., Furutjäll, S., Jern, C., Nielsen, H. H., Lambertsen, K. L., Eun, M.-Y., Ahn, J. W., Thanapornsangsuth, P., Rattanawong, W., Pujol-Calderón, F., Zetterberg, H., Blennow, K., Hahn, M., Uphaus, T., Gröschel, K., Tudisco, V., Klingbeil, J., Guthknecht, A., Abu-Rumeileh, S., Sacco, S., Foschi, M., D'Anna, L., Kuhle, J., Otto, M., & Caso, V. (2026). Diagnostic and prognostic value of blood neurofilament light chain in ischemic stroke: An individual patient data meta-analysis. Journal of Neurology. https://doi.org/10.1161/STROKEAHA.124.050508