Biochemical Biomarker Combinations in Human Traumatic Spinal Cord Injury: An Exploratory Study

Background/Objectives: Early diagnosis and prognosis after traumatic spinal cord injury (TSCI) remain challenging, and single biochemical biomarkers have shown limited stand-alone utility. Combining different biomarkers may improve prediction. We explored combinations of biomarkers in blood and cerebrospinal fluid (CSF) and their association with injury severity and neurological outcome after TSCI. Methods: In this post hoc analysis of a previously reported prospective cohort, blood and CSF were collected from 15 patients with TSCI at a median of 13 h after injury. Biomarkers comprised 13 inflammatory/structural proteins measured by quantitative assays and an Olink Target 96 Inflammation panel (92 proteins). Injury severity was classified by the American Spinal Injury Association (ASIA) Motor Score (AMS) at admission (admission injury severity) and at follow-up (follow-up neurological status). LASSO regression with 1000 repetitions identified combinations associated with level-adjusted AMS. Results: Of the quantitative assay biomarkers, interferon-γ (IFN-γ), interleukin (IL)-6 and IL-8 in blood and IFN-γ and IL-10 in CSF were frequently selected for admission injury severity, while IL-6, IL-8 and glial fibrillary acidic protein (GFAP) in blood and IFN-γ in CSF were selected for follow-up neurological status. Olink panel biomarkers varied substantially: Thymic stromal lymphopoietin (TSLP), matrix metalloproteinase-10 (MMP-10) and IL-17A in blood and C-C motif chemokine 3 (CCL3) in CSF were selected in admission injury severity models, and CCL20 and TSLP in blood and CCL3 in CSF were selected for follow-up neurological status. Forcing admission injury severity into the follow-up models reduced internally cross-validated prediction error by approximately 29-33% across all panels, suggesting that much of the apparent biomarker signal reflected admission injury severity rather than independent prognostic information. Only GFAP in blood retained a consistent association with follow-up neurological status when accounting for admission injury severity. Conclusions: In this small exploratory study, blood-based combinations of IFN-γ, IL-8 and IL-6 and CSF-based combinations of IFN-γ and IL-10 were associated with admission injury severity. Only GFAP in blood showed consistent prognostic value beyond admission severity. Selection frequencies and cross-validated estimates are internal and hypothesis-generating, not evidence of clinical utility or generalizability; independent validation is required.