Short- and long-term consequences of sport-related concussion

Abstract: Concussions are common in contact sports. Symptoms such as confusion and/or loss of consciousness following an impact to the head indicate that a sport-related concussion (SRC) has occurred. The symptoms normally resolve within 10-14 days following an SRC in adults although at least 10 % of athletes suffer from prolonged symptoms. Repeated SRCs have been linked to increased incidence of neurodegenerative disorders including tau aggregation, attributed to axonal injury and neuroinflammation. This thesis investigates the epidemiology and management of SRC in Swedish elite soccer, and pathophysiologic aspects of concussed athletes.In questionnaire-based studies, paper I (retrospective) and II (prospective), >1000 Swedish elite soccer players were evaluated. One third of players continued to play at time of SRC, in opposition to current guidelines. In addition, the concussion incidence (ca 1.19 /1000 game hours) was similar in males and females. However, females had a higher symptoms load at baseline, at time of SRC, and had a longer duration of symptoms than male players. In Papers III and IV, pathophysiological aspects were evaluated in young athletes with ≥ 3 previous SRCs, diagnosed with post-concussion syndrome, and moderate to severe traumatic brain injury (TBI) patients ≥6 month post-injury. We used 3T PET/MR in addition to blood and cerebrospinal fluid biomarkers, and cognitive evaluation. MR imaging (arterial spin labelling; ASL) was used to estimate cerebral blood flow (CBF) in Paper III. Here, increased TBI severity was associated with decreased total grey matter CBF, and female athletes had globally decreased CBF. In Paper IV, tau aggregations were investigated by the PET tracer THK5317, and microglial neuroinflammation by the PK11195 tracer. SRC athletes had increased tau in the corpus callosum, and increased neuroinflammation medially in the medial temporal lobes. In TBI patients, tau was increased in thalami, temporal white matter and midbrain, with widespread neuroinflammation in white matter tracts. The alterations of CBF, and increased tau and neuroinflammation, in persistently symptomatic SRC athletes may contribute to the pathophysiology of SRC and the risk of long-term consequences. However, to determine whether these changes are persistent, exacerbate with time or may resolve spontaneously longitudinal studies are required.