Impaired Cerebral Vasoreactivity Despite Symptom Resolution in Sports-Related Concussion

Traumatic brain injury (TBI) is associated with increased risk of later-life neurodegeneration and dementia. However, the underpinning mechanisms are poorly understood, and secondary injury resulting from perturbed physiological processes plays a significant role. Cerebral vasoreactivity (CVR), a measure of hemodynamic reserve, is known to be impaired in TBI. However, the temporal course of this physiological perturbation is not established. We examined CVR and clinical symptoms on day 3 (T1), day 21 (T2), and day 90 (T3) after concussion in collegiate athletes and cross-sectionally in non-injured controls. Changes in middle cerebral artery blood flow velocity (MCAV; transcranial Doppler ultrasonography) were measured during changes in end-tidal CO₂ (PetCO₂) at normocapnia, hypercapnia (inspiring 8% CO₂), and hypocapnia (hyperventilation). CVR was determined as the slope of the linear relationship and expressed as percent change in MCAV per mmHg change in PetCO₂. CVR was attenuated during the acute phase T1 (1.8 ± 0.4U; p = 0.0001), subacute phases T2 (2.0 ± 0.4U; p = 0.0017), and T3 (1.9 ± 0.6U; p = 0.023) post-concussion compared to the controls (2.3 ± 0.3U). Concussed athletes exhibited higher symptom number (2.5 ± 3.0 vs. 12.1 ± 7.0; p < 0.0001) and severity (4.2 ± 6.0 vs. 29.5 ± 23.0; p < 0.0001), higher Patient Health Questionnaire-9 score (2.2 ± 2.0 vs. 9.1 ± 6.0; p = 0.0003) at T1. However, by T2, symptoms had resolved. We show that CVR is impaired as early as 4 days and remains impaired up to 3 months post-injury despite symptom resolution. Persistent perturbations in CVR may therefore be involved in secondary injury. Future studies with a larger sample size and longer follow-up period are needed to validate this finding and delineate the duration of this vulnerable period.