Highlight
• Standard antiplatelet therapy demonstrated a significantly lower all-cause mortality compared to thrombolytic treatment in spontaneous SCI.
• No significant difference was found between the two approaches in hospital readmission or rehabilitation utilization at 180 days.
• Findings suggest potential risks from off-label thrombolytic use in SCI and underscore the need for high-quality, prospective studies.
• Propensity score matching adjusted for 68 clinical covariates, enhancing the validity of comparative outcome assessment.
Study Background
Spinal cord infarction (SCI) is a rare but devastating cause of acute myelopathy, accounting for a small fraction of all ischemic strokes. Its clinical presentation often involves sudden motor, sensory, and autonomic dysfunction, leading to substantial morbidity and disability. Unlike cerebral stroke, SCI lacks well-established acute therapeutic guidelines, in part due to its rarity and diagnostic challenges.
Thrombolytic therapy (using agents such as alteplase or tenecteplase) remains the standard in cerebral ischemic strokes when administered timely; however, its application in SCI is extrapolated without robust evidence, raising concerns about efficacy and safety in this distinct vascular territory. Conversely, standard care typically involves antiplatelet agents aimed at secondary prevention, but their role in acute management requires clarification.
Study Design
This investigation was a retrospective cohort study leveraging the TriNetX Global Collaborative Network database, which compiles electronic health record data from numerous healthcare institutions worldwide. Adult patients diagnosed with acute spontaneous SCI (identified using ICD-10 code G95.11) were included.
Patients were segregated into two groups based on acute treatment within 48 hours of diagnosis: one receiving standard antiplatelet therapy and the other receiving thrombolytic therapy with either alteplase or tenecteplase. Individuals undergoing aortic repair were excluded to minimize confounding by procedure-related ischemia.
To mitigate bias due to non-random treatment allocation, propensity score matching at a 1:1 ratio was performed, balancing 68 baseline covariates including demographics, comorbid conditions, and clinical parameters. The primary endpoint was all-cause mortality. Secondary exploratory analyses examined 180-day hospital readmission rates and rehabilitation service utilization. Sensitivity analyses and E value calculations addressed robustness of findings and potential confounding by unmeasured variables.
Key Findings
From the initial cohort, 965 patients received standard care, and 103 received thrombolysis; after matching, 96 patients remained in each group with comparable baseline characteristics.
The principal finding was a significantly lower all-cause mortality in the standard care group: 13.5% versus 29.2% in the thrombolysis group, corresponding to a hazard ratio of 0.423 (95% CI, 0.219-0.817; P=0.008). The Kaplan-Meier estimate showed 180-day survival rates of 84.3% for antiplatelet therapy versus 68.7% for thrombolytic therapy (log-rank P=0.008). The E value of 4.16 suggests that an unmeasured confounder would need a strong association with both treatment and mortality to negate these results.
No statistically significant differences emerged in secondary outcomes: readmission rates were 14.6% with standard care versus 16.7% with thrombolysis (P=0.669), and rehabilitation utilization was 43.8% versus 49.0% (P=0.507), respectively.
These results persisted across multiple sensitivity analyses, reinforcing the consistency of the mortality advantage with standard antiplatelet management.
Expert Commentary
The study addresses an important clinical gap in SCI management through a rigorous large-scale real-world data approach, enhancing applicability beyond single-center reports. The substantial mortality reduction associated with antiplatelet therapy challenges the widely held assumption that thrombolysis, beneficial in cerebral infarction, necessarily translates into SCI.
Biological plausibility supports cautious use of thrombolytics in SCI; the spinal cord’s vascular anatomy and fragility differ markedly from cerebral territory, potentially increasing hemorrhagic and reperfusion injury risks. Moreover, the rarity and heterogeneity of SCI likely contribute to uncertain thrombolytic benefit.
Nonetheless, limitations inherent to retrospective analyses remain. Residual confounding, despite extensive matching, cannot be excluded. Also, the relatively small thrombolysis group size limits definitive conclusions. The lack of granular neurological function data and imaging details is another limitation, precluding nuanced outcome interpretation.
Current guidelines do not specifically endorse thrombolysis in SCI due to insufficient evidence. This study furnishes compelling data to support conservative acute management with antiplatelets, pending randomized controlled trials.
Conclusion
This comprehensive propensity score-matched analysis indicates that in acute spontaneous spinal cord infarction, standard antiplatelet therapy is associated with significantly lower mortality compared to thrombolytic therapy, without compromising hospital readmissions or rehabilitation usage. These findings challenge the empirical off-label thrombolytic administration in SCI and suggest a preference for conservative treatment until prospective, controlled evidence becomes available.
Clinicians should weigh these emerging data carefully and advocate for inclusion of SCI patients in clinical trials to refine acute management standards, ultimately improving outcomes in this rare but severe condition.
Funding and Clinical Trials
The article did not disclose specific funding sources. No clinical trial registration is indicated as the study is retrospective.
References
1. AbuAlrob MA, Al-Salahat A, Zammar K, Al-Jerdi S. Standard Antiplatelet Therapy Versus Thrombolysis in Acute Spontaneous Spinal Cord Infarction: A Propensity Score-Matched Analysis. Stroke. 2026 Aug 3; PMID: 42544504.
2. Nedeltchev K, et al. Spinal cord ischemia: clinical and magnetic resonance imaging findings and short-term outcome. Arch Neurol. 2004 Aug;61(8):1112-8.
3. Novy J, et al. Spinal cord ischemia: clinical and imaging patterns, pathogenesis, and outcomes in 27 patients. Arch Neurol. 2006 Dec;63(12):1710-6.
4. Saver JL. Time is brain—quantified. Stroke. 2006 Jan;37(1):263-6.
