Sex‐Related Differences in the Effects of Sports‐Related Concussion: A Review

Abstract

Sports-related concussion is a serious health challenge, and females are at higher risk of sustaining a sports-related concussion compared to males. Although there are many studies that investigate outcomes following concussion, females remain an understudied population, despite representing a large proportion of the organized sports community. In this review, we provide a summary of studies that investigate sex-related differences in outcome following sports-related concussion. Moreover, we provide an introduction to the methods used to study sex-related differences after sports-related concussion, including common clinical and cognitive measures, neuroimaging techniques, as well as biomarkers. A literature search inclusive of articles published to March 2020 was performed using PubMed. The studies were reviewed and discussed with regard to the methods used. Findings from these studies remain mixed with regard to the effect of sex on clinical symptoms, concussion-related alterations in brain structure and function, and recovery trajectories. Nonetheless, there is initial evidence to suggest that sex-related differences following concussion are important to consider in efforts to develop objective biomarkers for the diagnosis and prognosis of concussion. Additional studies on this topic are, however, clearly needed to improve our understanding of sex-related differences following concussion, as well as to understand their neurobiological underpinnings. Such studies will help pave the way toward more personalized clinical management and treatment of sports-related concussion.

Sex-specific differences in resting-state functional brain activity in pediatric concussion

“…For example, a recent cohort study (n=986) found that female adolescents with concussion endorse more symptoms on the 22-item and widely used SCAT5 30 than concussed males, and are more likely to have a higher total symptom score 31 . Two large-scale, multi-center cohort studies have shown that females have a protracted recovery in comparison to males 28,29 , which align with other clinical data on disparate sex effects in concussion summarized in two recent systematic reviews 32,33 . Therefore, we studied sex-specific rs-fMRI differences in pediatric concussion to address an important knowledge gap, and advance our understanding of how the functional neuropathology of concussion differs between males and females.…”

The Neurophysiological Responses of Concussive Impacts: A Systematic Review and Meta-Analysis of Transcranial Magnetic Stimulation Studies

“…Another limitation in this review, which reflects the research into acute, post-acute, and long-term outcomes more generally, is that we could not analyze TMS data with regards to gender, asymptomatic vs. symptomatic, and the quantified number of concussions reported. Emerging evidence is suggesting that, following a concussion, females have greater severity of symptoms and may take longer to recover (Koerte et al, 2020 ); however, TMS studies have not specifically investigated this question by providing gender-specific TMS data. Similarly, an investigation of the number of concussions experienced has been limited with groups divided between “history of concussion” and “no history of concussion.” One study (De Beaumont et al, 2007 ), however, did compare multiple concussions (mean 2.7 ± 1.3) to those with only one reported concussion and age-matched controls, showing no differences in motor threshold, MEP amplitude, or cSP duration between concussed groups, with differences only being observed between both concussed groups to controls.…”

“…Another limitation in this review, which reflects the research into acute, post-acute, and long-term outcomes more generally, is that we could not analyze TMS data with regards to gender, asymptomatic vs. symptomatic, and the quantified number of concussions reported. Emerging evidence is suggesting that, following a concussion, females have greater severity of symptoms and may take longer to recover (Koerte et al, 2020); however, TMS studies have not specifically investigated this question by providing gender-specific TMS data. Similarly, an investigation of the number of concussions experienced has been limited with groups divided between "history of concussion" and "no history of concussion."…”

The ENIGMA sports injury working group:– an international collaboration to further our understanding of sport-related brain injury

“…Female athletes may report greater frequency and severity of symptoms and are at increased risk for developing persistent symptoms (Broshek et al 2005;Desai et al 2019;Iverson et al 2017). Differences in the way symptoms are being reported by males compared to females may play a role (Desai et al 2019;Dolle et al 2018;Iverson et al 2017;Koerte et al 2020). However, differences in symptoms may also be due to biological differences in brain structure and function that may lead to increased vulnerability of the female brain to shear forces (Dolle et al 2018) or differences in the neuroinflammatory response to trauma (Villapol et al 2017).…”