Circulating Neurofilament Light Chain Is Associated With Survival After Pediatric Cardiac Arrest

Objectives: To characterize neurofilament light levels in children who achieved return of spontaneous circulation following cardiac arrest compared with healthy controls and determine an association between neurofilament light levels and clinical outcomes.

Design: Retrospective cohort study.

Setting: Academic quaternary PICU.

Patients: Children with banked plasma samples from an acute respiratory distress syndrome biomarker study who achieved return of spontaneous circulation after a cardiac arrest and healthy controls.

Interventions: None.

Measurements And Main Results: Neurofilament light levels were determined with a highly sensitive single molecule array digital immunoassay. Patients were categorized into survivors and nonsurvivors and into favorable (Pediatric Cerebral Performance Category score of 1-2 or unchanged from baseline) or unfavorable (Pediatric Cerebral Performance Category score of 3-6 or Pediatric Cerebral Performance Category score change ≥1 from baseline). Associations between neurofilament light level and outcomes were determined using Wilcoxon rank-sum test. We enrolled 32 patients with cardiac arrest and 18 healthy controls. Demographics, severity of illness, and baseline Pediatric Cerebral Performance Category scores were similar between survivors and nonsurvivors. Healthy controls had lower median neurofilament light levels than patients after cardiac arrest (5.5 [interquartile range 5.0-8.2] vs 31.0 [12.0-338.6]; p < 0.001). Neurofilament light levels were higher in nonsurvivors than survivors (78.5 [26.2-509.1] vs 12.4 [10.3-28.2]; p = 0.012) and higher in survivors than healthy controls (p = 0.009). The four patients who survived with a favorable outcome had neurofilament light levels that were not different from patients with unfavorable outcomes (21.9 [8.5--35.7] vs 37.2 [15.4-419.1]; p = 0.60) although two of the four patients who survived with favorable outcomes had progressive encephalopathies with both baseline and postcardiac arrest Pediatric Cerebral Performance Category scores of 4.

Conclusions: Neurofilament light is a blood biomarker of hypoxic-ischemic brain injury and may help predict survival and neurologic outcome after pediatric cardiac arrest. Further study in a larger, dedicated cardiac arrest cohort with serial longitudinal measurements is warranted.