Neuroinflammation found in athletes with persistent post-concussive symptoms (PPCS)

By Padmini Konidena. This article was initially published in our Concussion Update newsletter; please consider subscribing.

A study published in the Journal of Neuroinflammation found that athletes with PPCS due to sports-related concussions (SRC) have elevated levels of inflammation in the brain. Of 27 cerebrospinal fluid (CSF) biomarkers of inflammation tested for, eight were significantly higher in athletes with PPCS compared to healthy controls. The 24 athletes who participated had sustained a median of 5 sports-related concussions and experienced “many and severe” long-term symptoms (≥ 6 months).

During the event that causes a concussion (a mild traumatic brain injury), the brain cells stretch and shear, leading to neuroinflammation that exacerbates the brain’s difficulties in dealing with the damage from the initial injury event. Ann Gard et al. note, “Based on CSF inflammatory marker profiling we find signs of ongoing neuroinflammation persisting months to years after the last SRC in athletes with persistent post-concussive symptoms.” Since neuroinflammation may be responsible for PPCS, the researchers believe studies involving treatments targeting the inflammation would benefit patients.

Gard et al. recruited participants from two hospitals and chose them because their PPCS prevented participation in sports and limited other social interactions for longer than six months. Athletes sustained their latest concussion a median of 17 months before the tests and were an average age of 26. The 12 control participants were age and sex-matched to the athletes. Since the athletes could not exercise, Gard et al. chose controls who exercised less than twice per week and told them to abstain from exercise for seven days before the spinal tap. 

The researchers used a spinal tap to collect cerebrospinal fluid (liquid surrounding the brain and spine), which contains markers of inflammation. The inflammatory response was observed to last months or years after the athletes’ latest concussion, with one participant having their latest concussion eight years before the spinal tap. The long-lasting inflammation could be because athletes sustained multiple concussions and have an elevated body temperature during exercise, leading to a higher susceptibility for brain tissue to respond poorly to a concussion.

Since neuroinflammation may be responsible for PPCS, the researchers believe studies involving treatments targeting the inflammation would benefit patients. If treatment targeting inflammation reduces PPCS, then there could be a causal link between the two. 

Limitations of the study include the small cohort and the lack of a control group comprised of athletes who have sustained concussions but do not have PPCS. However, for those with PPCS, a treatment targeting inflammation would dramatically increase their quality of life as they could return to work, school, and maybe even sports.