Longitudinal Plasma Biomarker Profiles Predict Neurological Outcome in Traumatic Spinal Cord Injury

OBJECTIVE: Traumatic spinal cord injury (SCI) is diagnosed by imaging and clinical scoring using the American Spinal Injury Association Impairment Scale (AIS). These methods have limited value for prognosis. Here, the prognostic value of plasma neurofilament-light (NfL), glial fibrillary acidic protein (GFAP), and contactin-1 (CNTN-1) was analyzed. METHODS: Biomarker levels were determined in the plasma of traumatic SCI patients (n = 37) and healthy controls (n = 22). SCI samples (n = 112) were collected at different time points from 0 to 4 days to 18 weeks post-injury. NfL and GFAP were measured by single molecule array (Simoa) technology, CNTN-1 by Luminex. Baseline and outcome AIS and motor scores were collected as a measure of injury severity. RESULTS: NfL, GFAP, and CNTN-1 showed different kinetics in SCI patients over time. Baseline biomarker levels could identify AIS-A SCI patients (NfL + GFAP) and discriminate between patients with a motor score change <5 and those with a change ≥5 (NfL + GFAP+CNTN-1). Longitudinally, NfL could identify AIS-A patients up to 12 weeks post-SCI and discriminate between patients with a motor score change <5 and those with a change ≥5 up to 18 weeks post-SCI. Further, baseline biomarker levels positively (NfL + GFAP) or negatively (CNTN-1) correlated with outcome injury severity and together could accurately predict AIS conversion (AUC 0.863) and motor score change (AUC 0.857). This predictive ability was maintained in subacute/chronic SCI stages. INTERPRETATION: In conclusion, plasma NfL, GFAP, and CNTN-1 are potential prognostic biomarkers in SCI. This is important for patient stratification in clinical trials, prediction of neurological outcome and informed decision-making in SCI treatment and rehabilitation. ANN NEUROL 2025;97:1180-1189.