Blood NfL in Ischemic Stroke: Diagnostic and Prognostic Signals

Key Takeaways

• Diagnostic discrimination was high for ischemic stroke versus healthy controls with AUC 0.79-0.97 and fair for ischemic stroke versus transient ischemic attack with AUC 0.64-0.80.
• Higher day 1 NfL was associated with symptomatic intracranial hemorrhage, and from day 2 onward higher values were associated with larger infarct lesion volume.
• Higher NfL independently predicted mRS greater than 2 and mortality at 3 months.

In ischemic stroke, the median NfL Z-score rose from 2.0 at day 1 to 3.5 at day 6-7 in an individual patient data meta-analysis of blood neurofilament light chain in adults. The pooled analysis examined biomarker behavior across prespecified post-onset windows and evaluated diagnostic discrimination and outcome associations within the same framework. Adults with ischemic stroke were the main population of interest. Blood NfL showed a clear time-dependent pattern after stroke onset.

The literature search included adults with blood NfL measured within 30 days after ischemic stroke onset. Values were converted to age- and BMI-adjusted Z-scores derived from a previously published healthy-control reference population. Clinical, radiological, and biochemical parameters were also collected, and the dataset included 4,081 blood NfL values from 2,872 participants. It included 1,985 with ischemic stroke, 88 with transient ischemic attack, and 799 healthy controls from 18 published studies and 3 unpublished cohorts. Prespecified windows were across the first month after onset.

Across these windows, NfL Z-scores increased progressively from day 1 through day 6-7 in patients with ischemic stroke. That rise coincided with measurable separation between ischemic stroke and comparator groups. Diagnostic discrimination was high for ischemic stroke versus healthy controls, with AUC values ranging from 0.79-0.97. Discrimination for ischemic stroke versus transient ischemic attack was fair, with AUC values ranging from 0.64-0.80.

Higher day 1 NfL Z-score was associated with symptomatic intracranial hemorrhage, with aOR 1.33 and p=0.014. From day 2 onward, higher NfL Z-scores were associated with larger infarct lesion volume, with the strongest reported correlation at day 6-7 at Spearman rho 0.795. Higher values also independently predicted modified Rankin Scale scores above 2 at 3 months, with aOR 1.31 and p<0.001. They also independently predicted mortality at 3 months, with aOR 1.67 and p<0.001.

Overall, blood NfL was progressively elevated after ischemic stroke and carried prognostic value for in-hospital complications and 3-month clinical outcomes in the pooled data. The pooled findings describe blood NfL as a time-dependent marker with diagnostic discrimination and prognostic associations after ischemic stroke.