Physical trauma and risk of multiple sclerosis: a systematic review and meta-analysis of observational studies.

Background: We aimed to examine physical trauma as a risk factor for the subsequent diagnosis of MS.

Methods: We searched for observational studies that evaluated the risk for developing MS after physical trauma that occurred in childhood (≤20 years) or "premorbid" (>20 years). We performed a meta-analysis using a random effects model.

Results: We identified 1362 individual studies, of which 36 case-control studies and 4 cohort studies met the inclusion criteria for the review. In high quality case-control studies, there were statistically significant associations between those sustaining head trauma in childhood (OR=1.27; 95% CI, 1.12-1.44; p<0.001), premorbid head trauma (OR=1.40; 95% CI, 1.08-1.81; p=0.01), and other traumas during childhood (OR=2.31; 95% CI, 1.06-5.04; p=0.04) and the risk of being diagnosed with MS. In lesser quality studies, there was a statistical association between "other traumas" premorbid and spinal injury premorbid. No association was found between spinal injury during childhood, or fractures and burns at any age and the diagnosis of MS. The pooled OR of four cohort studies looking at premorbid head trauma was not statistically significant.

Conclusions: The result of the meta-analyses of high quality case-control studies suggests a statistically significant association between premorbid head trauma and the risk for developing MS. However, cohort studies did not. Future prospective studies that define trauma based on validated instruments, and include frequency of traumas per study participant, are needed.