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Background <p>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.</p> Methods <p>We performed a systematic literature search of studies on blood NfL measured in adult patients within 30&#xa0;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: &lt; 24&#xa0;h; D2: 24–48&#xa0;h; D3: 48–72&#xa0;h; D4–5: 72–120&#xa0;h; D6–7: 120–168&#xa0;h; D8–30: &gt; 168&#xa0;h) with baseline characteristics and 3-month follow-up outcomes (modified Rankin Scale, mRS; survival).</p> Results <p>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participants (IS n = 1985, transient ischemic attack n = 88, healthy controls n = 799) of 18 published studies and 3 unpublished cohorts.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 &gt; 2 (aOR = 1.31, p &lt; 0.001) and mortality (aOR = 1.67, p &lt; 0.001) at 3&#xa0;months.</p> Conclusions <p>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.</p>

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

  • 期刊论文

  • 发表日期：

    2026年5月16日

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  • 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

摘要

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.