Diagnosis and monitoring of sport-related concussion

Abstract: Background: Concussions are one of the most common sport-related injuries and it is known that they cause axonal and glial damage, and that there are risks for long-term effects. The aims of this thesis were to find possible methods, which may help clinicians to diagnose and monitor mild traumatic brain injury (TBI), analyse the APOEε4 allele genotype that has been associated with poor outcome after TBI and evaluate the relationship between neuropsychological assessment and brain injury biomarkers in the cerebrospinal fluid (CSF). Methods: In paper I-IV, 30 amateur boxers and 25 non-boxing matched controls were included. All study subjects underwent medical and neurological examination, neuropsychological evaluation and ApoE genotyping. Brain injury biomarkers were analysed in CSF and blood 1-6 days after a bout and after a rest period for at least 14 days. The controls were tested once. Paper V presents a knocked out boxer where CSF brain injury biomarkers were analysed at five time points upon normalization. Results: The CSF concentrations of neurofilament light (NFL), phosphorylated NFH (pNFH), glial fibrillary acidic protein (GFAP), Total-tau and S100B and plasma-tau were significantly increased 1-6 days after bout compared to controls. NFL, pNFH and GFAP remained elevated after the rest period. Possession of APOEε4 allele did not influence biomarker concentrations. The neurological assessment showed no significant differences between boxers and controls, however boxers with elevated CSF NFL by follow up performed significantly poorer on the Trailmaking A and Simple Reaction Time tests. The case report in paper V showed marked elevation of CSF NFL, with a peak at 2 weeks post trauma, not reaching below the reference limit until week 36. Conclusion: This thesis found that the subconcussive trauma in amateur boxing causes axonal and glial brain injury, even without unconsciousness or concussion symptoms. The neuropsychological evaluation without baseline testing is not as sensitive as CSF NFL in the diagnosis and monitoring of concussion. ApoE genotype was not found to influence CSF biomarker concentrations. The case report further showed that recovery from concussion, although in absence of symptoms, could take more than 4 months. The results of this thesis indicate, that NFL and other CSF biomarkers may be valuable in the management of injured athletes and in return-to-play decisions following concussion.