Diagnostic and prognostic value of blood neurofilament light chain in ischemic stroke: an individual patient data meta-analysis.
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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, Rattanawong Wanakorn, 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
Аннотация
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participants (IS n = 1985, transient ischemic attack n = 88, healthy controls n = 799) of 18 published studies and 3 unpublished cohorts.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.