Abstract
Current assessments of recovery following spinal cord injury (SCI) focus on clinical outcome measures. These assessments bear an inherent risk of bias, emphasizing the need for more reliable prognostic biomarkers to measure SCI severity. This study evaluated fluid biomarkers as an objective tool to aid with prognosticating outcomes following SCI. Using a (1)H nuclear magnetic resonance (NMR)-based quantitative metabolomics approach of urine samples, the objectives were to determine (a) if alterations in metabolic profiles reflect the extent of recovery of individual SCI patients, (b) whether changes in urine metabolites correlate to patient outcomes, and (c) whether biological pathway analysis reflects mechanisms of neural damage and repair. An inception cohort exploratory pilot study collected morning urine samples from male SCI patients (n=6) following injury and again at 6-months post-injury. A 700 MHz Bruker Avance III HD NMR spectrometer was used to acquire the metabolic signatures of urine samples, which were used to derive metabolic pathways. Multivariate statistical analyses were used to identify changes in metabolic signatures, which were correlated to clinical outcomes in the Spinal Cord Independence Measure (SCIM). Among SCI-induced metabolic changes, biomarkers which significantly correlated to patient SCIM scores included caffeine (R = -0.76, p < 0.01), 3-hydroxymandelic acid (R= -0.85, p < 0.001), L-valine (R = 0.90, p < 0.001; R = -0.64, p < 0.05), and N-methylhydantoin (R = -0.90, p < 0.001). The most affected pathway was purine metabolism. These findings indicate that urinary metabolites reflect SCI lesion severity and recovery and provide potentially prognostic biomarkers of SCI outcome in precision medicine approaches.