The effect of early mobilisation (< 14 days) on pathophysiological and functional outcomes in animals with induced spinal cord injury: a systematic review with meta-analysis.

ABSTRACT

INTRODUCTION: The optimum time to mobilise (standing, walking) following spinal cord injury (SCI) is unknown but may have implications for patient outcomes. There are no high-quality experimental studies that examine this issue, with a paucity of guidance for clinicians. Pre-clinical studies lead research in this field and can contribute to knowledge and support future clinical practice. OBJECTIVE: to evaluate the effect of early compared to no mobilisation on pathophysiological and functional outcomes in animals with induced SCI. METHODS: A systematic review with meta-analysis was conducted by searching pre-clinical literature in MEDLINE (PubMed), Embase (Ovid), Web of Science, OpenGrey, and EThOS (June 2023). Studies were included of any research method giving numerical results comparing pathophysiological and functional outcomes in rats and mice mobilised within 14-days of induced SCI to those that did not mobilise. Data were synthesised using random-effects meta-analyses. The quality of the evidence was assessed using the CAMARADES checklist. The certainty of findings was reported using the GRADE approach. This study is registered on PROSPERO (CRD42023437494). RESULTS: Seventeen studies met the inclusion criteria. Outcomes found that Brain Derived Neurotrophic Factor levels were greater in those that initiated mobilisation within 14-days of SCI compared to the groups that did not. Mobilisation initiated within 14-days of SCI was also associated with statistically significant functional gains (Basso, Beattie and Bresnahan locomotor rating score (BBB) = 2.13(0-21), CI 1.43, 2.84, Ladder Rung Walking Task = - 12.38(0-100), CI 20.01, - 4.76). Meta-analysis identified the greatest functional gains when mobilisation was initiated within 3 days of SCI (BBB = 3.00, CI 2.31-3.69, p < 0.001), or when delivered at low intensity (BBB = 2.88, CI 2.03-3.70, p < 0.001). Confidence in the findings from this review was low to moderate due to the risk of bias and mixed methodological quality. CONCLUSION: Mobilisation instigated within 14-days of injury, may be an effective way of improving functional outcomes in animal models following SCI, with delays potentially detrimental to recovery. Outcomes from this study support further research in this field to guide future clinical practice.