The effects of cytomegalovirus on brain structure following sport-related concussion. Brain 2023 Oct 03;146(10):4262-4273
Date
04/19/2023Pubmed ID
37070698Pubmed Central ID
PMC10545519DOI
10.1093/brain/awad126Scopus ID
2-s2.0-85158119562 (requires institutional sign-in at Scopus site) 4 CitationsAbstract
The neurotrophic herpes virus cytomegalovirus is a known cause of neuropathology in utero and in immunocompromised populations. Cytomegalovirus is reactivated by stress and inflammation, possibly explaining the emerging evidence linking it to subtle brain changes in the context of more minor disturbances of immune function. Even mild forms of traumatic brain injury, including sport-related concussion, are major physiological stressors that produce neuroinflammation. In theory, concussion could predispose to the reactivation of cytomegalovirus and amplify the effects of physical injury on brain structure. However, to our knowledge this hypothesis remains untested. This study evaluated the effect of cytomegalovirus serostatus on white and grey matter structure in a prospective study of athletes with concussion and matched contact-sport controls. Athletes who sustained concussion (n = 88) completed MRI at 1, 8, 15 and 45 days post-injury; matched uninjured athletes (n = 73) completed similar visits. Cytomegalovirus serostatus was determined by measuring serum IgG antibodies (n = 30 concussed athletes and n = 21 controls were seropositive). Inverse probability of treatment weighting was used to adjust for confounding factors between athletes with and without cytomegalovirus. White matter microstructure was assessed using diffusion kurtosis imaging metrics in regions previously shown to be sensitive to concussion. T1-weighted images were used to quantify mean cortical thickness and total surface area. Concussion-related symptoms, psychological distress, and serum concentration of C-reactive protein at 1 day post-injury were included as exploratory outcomes. Planned contrasts compared the effects of cytomegalovirus seropositivity in athletes with concussion and controls, separately. There was a significant effect of cytomegalovirus on axial and radial kurtosis in athletes with concussion but not controls. Cytomegalovirus positive athletes with concussion showed greater axial (P = 0.007, d = 0.44) and radial (P = 0.010, d = 0.41) kurtosis than cytomegalovirus negative athletes with concussion. Similarly, there was a significant association of cytomegalovirus with cortical thickness in athletes with concussion but not controls. Cytomegalovirus positive athletes with concussion had reduced mean cortical thickness of the right hemisphere (P = 0.009, d = 0.42) compared with cytomegalovirus negative athletes with concussion and showed a similar trend for the left hemisphere (P = 0.036, d = 0.33). There was no significant effect of cytomegalovirus on kurtosis fractional anisotropy, surface area, symptoms and C-reactive protein. The results raise the possibility that cytomegalovirus infection contributes to structural brain abnormalities in the aftermath of concussion perhaps via an amplification of concussion-associated neuroinflammation. More work is needed to identify the biological pathways underlying this process and to clarify the clinical relevance of this putative viral effect.
Author List
Savitz J, Goeckner BD, Ford BN, Kent Teague T, Zheng H, Harezlak J, Mannix R, Tugan Muftuler L, Brett BL, McCrea MA, Meier TBAuthors
Benjamin Brett PhD Assistant Professor in the Neurosurgery department at Medical College of WisconsinMichael McCrea PhD Professor in the Neurosurgery department at Medical College of Wisconsin
Timothy B. Meier PhD Associate Professor in the Neurosurgery department at Medical College of Wisconsin
Lutfi Tugan Muftuler PhD Professor in the Neurosurgery department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AthletesAthletic Injuries
Brain
Brain Concussion
C-Reactive Protein
Cytomegalovirus
Humans
Prospective Studies
