Cerebrospinal Fluid Biomarkers of Injury in Patients with Isolated Spinal Cord Injury vs. Concomitant Mild Traumatic Brain Injury and Spinal Cord Injury

Introduction: In SCI patients, 40% to 74% also have mild TBI, which may be underdiagnosed. Reports indicate that the presence of SCI in patients with mild TBI negatively impacts full recovery. The role of simultaneous SCI in exacerbating neurological deficits in TBI patients remains largely unexplored. This study aims to evaluate the ability of cerebrospinal fluid (CSF) biomarkers to differentiate between mild TBI with SCI (mildTBI+SCI) and isolated SCI.

Methods: CSF samples were collected at multiple points post-injury (24hr, 36hr, 48hr, 60hr, 72hr, 84hr, and 96hr) from two patients with isolated cervical SCI (ASIA B) and three patients with combined TBI and cervical SCI (GCS >13, ASIA B). Samples were obtained via lumbar drain and analyzed using a multiplex immunoassay targeting 115 analytes, including cytokines, chemokines, growth factors, and biomarkers of endothelial dysfunction. Hedges’ g effect size was calculated for all analytes across time points to identify molecules that differentiate mildTBI+SCI from isolated SCI.

Results: The analytes with the highest Hedges’ g effect sizes, indicating the best separation between mildTBI+SCI and isolated SCI, were VEGF-C (effect size 2.8; 24hr p = 0.03, 36hr p = 0.07, 48hr p = 0.05, 60hr p = 0.01, 72hr p = 0.26, 84hr p = 0.06, 96hr p = 0.17), S-FAS (effect size 2.19; 24hr p = 0.01, 36hr p = 0.08, 48hr p = 0.01, 60hr p = 0.02, 72hr p = 0.2, 84hr p = 0.08, 96hr p = 0.06), and IFN-G (effect size 2.92; 24hr p = 0.07, 36hr p = 0.04, 48hr p = 0.01, 60hr p = 0.03, 72hr p = 0.12, 84hr p = 0.11, 96hr p = 0.02).

Conclusion : This study demonstrates the potential to distinguish mildTBI+SCI from isolated SCI with similar ASIA grades. Given the growing evidence that concomitant injuries behave as an independent entity, these biomarkers could be useful in selecting candidates for targeted therapies. The large effect sizes observed warrant further validation with larger sample sizes.