Neuroprotective Interventions for Acute Traumatic Spinal Cord Injury: A Systematic Review of Randomized Trials with Limited Meta-Analysis

Background/Objectives: Secondary injury after acute traumatic spinal cord injury (SCI) evolves over hours to weeks; no adjunctive neuroprotective therapy is standard care. This review aimed to assess the benefits and harms of neuroprotective interventions first given within 14 days of injury. Methods: We searched PubMed, Embase, Scopus, CENTRAL and four trial registers (16–21 May 2026) for randomized trials of neuroprotective interventions versus inactive or active comparators. Synthesis was by comparison, with meta-analysis only where grouping rules allowed. Risk of bias was assessed with RoB 2 and certainty with GRADE (PROSPERO CRD420261442429). Results: Thirty-four trials (about 3700 participants) were included: 26 pharmacologic, three biologic and five physiologic or procedural. Each prespecified synthesis group held one trial, limiting pooling to four exploratory two-trial riluzole analyses. Of 40 graded estimates, one had Moderate certainty, 17 Low and 22 Very low, mainly because of imprecision. In cervical injury, riluzole may result in little to no difference in motor recovery (mean difference 3.60 points, 95% CI −1.66 to 8.86; 0.97 allowing for baseline imbalance) or mortality (risk ratio 0.83, 0.39 to 1.77) and may slightly improve functional independence (4.32 points, −2.07 to 10.70), all with Low certainty. In complete injury, autologous macrophages given on days 9–17 probably make little to no difference in motor recovery (Moderate certainty). Conclusions: No neuroprotective intervention for acute traumatic SCI has Moderate- or High-certainty evidence of benefit, and evidence on serious harms is too sparse to judge safety. Larger trials with harmonized outcomes, precise timing and complete harms reporting are needed.