Individual patient data meta-analysis links blood neurofilament light chain levels to ischemic stroke outcomes

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participants (IS n = 1985, transient ischemic attack n = 88, healthy controls n = 799) of 18 published studies and 3 unpublished cohorts.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