Cardiovascular

Longitudinal dynamics of serum neurofilament light chain and prognostic value for functional outcome after acute stroke: a prospective cohort study.

TL;DR

sNfL levels increased during the first week after acute stroke, and higher D1 sNfL was associated with poor functional outcome at 3 and 6 months, suggesting potential value for early prognostic assessment.

Key Findings

Serum NfL rose significantly from within 24 h of onset (D1) to day 7 (D7) in patients with acute stroke.

  • The abstract reports that sNfL increased significantly from D1 to D7 (p < 0.001).
  • The cohort comprised 104 acute stroke patients: ICH (n = 28), ischemic stroke with intravenous thrombolysis (IS+IVT, n = 33), and ischemic stroke without thrombolysis (IS-IVT, n = 43).
  • sNfL was measured at D1 (within 24 h of onset) and at D7, and analyzed with linear mixed-effects models.

Patients with stroke had higher sNfL than healthy controls at D1.

  • The comparison was between 104 patients with acute stroke and 86 healthy controls (HCs).
  • The difference at D1 was reported as p < 0.001.
  • Enrollment was consecutive between January 2023 and December 2024.

Longitudinal sNfL trajectories did not differ significantly among the ICH, IS+IVT, and IS-IVT groups.

  • In the linear mixed-effects model adjusted for age and admission NIHSS score, the time × group interaction was p = 0.225.
  • The authors note that the predominantly mild-to-moderate severity profile of the cohort may have limited detection of trajectory differences.

Higher D1 sNfL was independently associated with higher odds of poor functional outcome at 3 months (primary endpoint).

  • Each 10-pg/mL increase in D1 sNfL was associated with 5% higher odds of poor outcome (OR = 1.05; 95% CI, 1.00-1.12; p = 0.047).
  • Poor functional outcome was assessed by the modified Rankin Scale at 3 months.
  • Estimates came from multivariable logistic regression; the lower confidence limit is at 1.00, so the association is borderline.

Higher D1 sNfL was independently associated with higher odds of poor functional outcome at 6 months (secondary endpoint).

  • Each 10-pg/mL increase in D1 sNfL was associated with 7% higher odds (OR = 1.07; 95% CI, 1.01-1.14; p = 0.025).
  • Outcome was assessed by mRS at 6 months using multivariable logistic regression.

D7 sNfL was not independently associated with poor functional outcome after adjustment.

  • This was reported for the multivariable logistic regression models.
  • In contrast, D1 sNfL showed significant associations at both 3 and 6 months.

Exploratory restricted cubic spline analyses found no evidence of nonlinearity for D1 sNfL but suggested a nonlinear association between D7 sNfL and 3-month poor outcome.

  • RCS and interaction analyses were prespecified as exploratory.
  • For D1 sNfL, there was no statistical evidence of nonlinearity.
  • For D7 sNfL, the relationship with 3-month poor functional outcome appeared nonlinear.

What This Means

This study followed 104 people who had an acute stroke (bleeding in the brain, or a clot-related stroke with or without clot-busting treatment) and compared them with 86 healthy people. Researchers measured neurofilament light chain (NfL), a protein released into the blood when nerve fibers are damaged, within 24 hours of the stroke and again on day 7. They then checked how well patients recovered at 3 and 6 months using a standard disability scale. NfL levels were higher in stroke patients than in healthy people at the start and rose further during the first week. The pattern of change was not clearly different among the three stroke types, though the patients were mostly mildly to moderately affected, which may have hidden differences. People with higher NfL in the first 24 hours were somewhat more likely to have a poor recovery: each 10 pg/mL increase was linked to about 5% higher odds of poor outcome at 3 months and 7% at 6 months. The 3-month result was borderline statistically. NfL measured at day 7 did not independently predict outcome after accounting for other factors. This research suggests that an early blood test for NfL might help in assessing likely recovery after stroke. However, the effects were modest, the sample was small, and some analyses were exploratory, so larger studies would be needed to confirm whether it adds useful information in practice.

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Citation

Chen G, Zhu Y, Chen F, Zhang C, Huang J, Wu W, et al.. (2026). Longitudinal dynamics of serum neurofilament light chain and prognostic value for functional outcome after acute stroke: a prospective cohort study.. Frontiers in neurology. https://doi.org/10.3389/fneur.2026.1932102