The impact of timing, dosage, and duration of high-dose methylprednisolone on neurological recovery and complications in acute spinal cord injury: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND

The role of high-dose methylprednisolone sodium succinate (MPSS) in acute traumatic spinal cord injury (SCI) remains controversial, particularly regarding optimal timing and duration. This study systematically evaluated randomized controlled trial (RCT) evidence on the effects of MPSS timing, dosage, and duration on neurological recovery and complications.

METHODS

A PRISMA-compliant systematic review and meta-analysis was conducted. PubMed, Embase, CENTRAL, Scopus, and Web of Science were searched from 1990 to March 2025. RCTs evaluating high-dose MPSS in acute traumatic SCI were included. The primary outcome was neurological recovery assessed by motor score improvement. The secondary outcomes included infectious complications, gastrointestinal bleeding, hypoglycemia, and mortality. Pooled effect estimates with 95% confidence intervals (CI) were calculated, with risk of bias assessed using the Cochrane RoB 2 tool and certainty of evidence using GRADE.

RESULTS

Eight RCTs involving 1379 patients were included. MPSS administered within 8 h of injury was associated with greater motor score improvement compared with placebo (mean difference 4.44 points; 95% CI 0.96-7.93; I2 = 0%). No neurological benefit was observed when MPSS was initiated after 8 h. Extending infusion from 24 to 48 h did not improve neurological outcomes and was associated with higher rates of serious infectious complications. Mortality did not differ significantly between the MPSS and control groups.

CONCLUSION

Early high-dose MPSS administration within 8 h of acute SCI is associated with modest neurological improvement, whereas delayed treatment offers no benefit. Prolonged infusion beyond 24 h increases complications without improving outcomes, supporting early, time-limited use when MPSS is selected.