Observations from a prospective small cohort study suggest that CGRP genes contribute to acute posttraumatic headache burden after concussion.

Introduction: Post-traumatic headache (PTH) is commonly reported after concussion. Calcitonin gene-related peptide (CGRP) is implicated in the pathogenesis of migraine. We explored how single nucleotide polymorphisms (SNPs) from CGRP-alpha (CALCA) and the receptor activity modifying protein-1 (RAMP1) related to headache burden during the first week after concussion. Methods: A prospective study was performed in 34 collegiate athletes who sustained a concussion. Participants completed the symptom evaluation checklist from the SCAT3 within 48 h of injury (V1), and again 4 (V2) and 7 (V3) days after injury. For each visit, the self-reported score (0-6) for headache, pressure in head, blurred vision, and sensitivity to light/noise were reported and summed to calculate the headache burden. A saliva sample was obtained and genotyped for CALCA (rs3781719) and RAMP1 (rs10185142). RAMP1 (TT, TC, CC) and CALCA (AA, AG, GG) were dichotomized (A+, A- and T+, T-, respectively), and concatenated (T+A+, T+A-, T-A+, T-A-) for analyses. Results: Headache Burden at Visit 1 was greatest in T+A+ compared to T-A+, and trended toward a significant difference with T+A-. Repeated-measures ANOVA revealed the presence of significant visit main effects (p < 0.001, η2 = 0.404), but the group (p = 0.055) and interaction effects only trended (p = 0.094). Pearson's χ2-tests revealed that 88% of those with return-to play (RTP) exclusions ≥15 days had PTH with multi-sensory symptoms (PTH+SENS) as compared to 35% in those with RTP < 14 day. Conclusion: Knowledge of RAMP1 and CALCA genotypes appear to improve an understanding the presenting features and magnitude of headache burden after concussion injury.

Use of Mayer wave activity to demonstrate aberrant cardiovascular autonomic control following sports concussion injury.

Dysregulation of cardiovascular autonomic control is gaining recognition as a prevailing consequence of concussion injury. Characterizing the presence of autonomic dysfunction in concussed persons is inconsistent and conventional metrics of autonomic function cannot differentiate the presence/absence of injury. Mayer wave (MW) activity originates through baroreflex adjustments to blood pressure (BP) oscillations that appear in the low-frequency (LF: 0.04-0.15 Hz) band of the BP and heart rate (HR) power spectrum after a fast Fourier transform. We prospectively explored MW activity (∼0.1 Hz) in 19 concussed and 19 noninjured athletes for 5 min while seated at rest within 48 h and 1 week of injury. MW activity was derived from the LF band of continuous digital electrocardiogram and beat-to-beat BP signals (LFHR, LF-SBP, MWHR, and MW-SBP, respectively); a proportion between MWBP and MWHR was computed (cMW). At 48 h, the concussion group had a significantly lower MWBP and cMW than controls; these differences were gone by 1 week. MWHR, LFHR, and LF-SBP were not different between groups at either visit. Attenuated sympathetic vasomotor tone was present and the central autonomic mechanisms regulating MW activity to the heart and peripheral vasculature became transiently discordant early after concussion with apparent resolution by 1 week.

Preliminary Evidence for a Window of Increased Vulnerability to Sustain a Concussion in Females: A Brief Report.

A difference exists between sexes for the incidence of concussion injuries and severity of post-injury outcomes with females having a higher incidence rate (in comparable sports) and experience more robust symptoms than males. The basis for this disparity has remained largely unresolved. Recent findings point to a potential biological mechanism that may be related to the menstrual cycle as an arbiter of post-injury outcomes. What has not been addressed, is whether the phase of menstrual cycle (inferred fluctuations of ovarian hormones) contributes to an increased vulnerability to sustain a concussion injury. This prospective, observational study sought to determine if concussions occurred at different frequencies throughout the phase of the menstrual cycle. Female athletes who sustained a concussion injury were queried three times over the 7-day study (e.g., within 48 h of injury, and 4 and 7 days after injury) to recall the number of days that have elapsed since the beginning of their most recent menstruation. Twenty female athletes enrolled after sustaining a concussion; 18 were eumenorrheic and 2 amenorrheic. Among eumenorrheic participants at the time of injury, 2 were in the follicular phase, 4 were in the early luteal phase and 9 were in the late luteal phase. Two athletes were injured on the first and 1 was injured on the second day of menstruation. The greatest number of concussions were sustained during the late luteal phase and during the first 2 days of menstruation. This 9-day window accounted for 2/3rd of the sustained concussions in our study.

Attenuation of Spontaneous Baroreceptor Sensitivity after Concussion.

INTRODUCTION: Cardiovascular autonomic nervous system (CV-ANS) function is negatively impacted after concussion. The arterial baroreflex buffers pressor and depressor challenges through efferent modulation of cardiac chronotropism and inotropism, and peripheral vascular tone. Baroreceptor sensitivity (BRS) reflects the capacity of the CV-ANS to accommodate dynamic metabolic demands in the periphery. The impact of concussion on BRS has yet to be defined. METHODS: Cardiovascular autonomic nervous system assessment (e.g., electrocardiogram and beat-to-beat systolic blood pressure [SBP]) was performed the seated upright position at rest within 48 h (V1) of concussion and 1 wk later (V2) in 10 intercollegiate male athletes with concussion and 10 noninjured male athletes. Changes in HR, SBP, high- and low-frequency HR variabilities (HF-HRV and LF-HRV, respectively), LF-SBP variability and BRS for increasing (BRSn-Up) and decreasing (BRSn-Dn) SBP excursions, and overall BRS (BRSn-Avg) were assessed for differences at V1 and V2. RESULTS: The concussion (age, 20 ± 1 yr; height, 1.79 ± 0.14 m; weight, 83 ± 10 kg) and control (age, 20 ± 1 yr; height, 1.78 ± 0.10 m; weight, 79 ± 13 kg) groups were matched for demographics. Concussed athletes had a significantly reduced BRSn-Up, BRSn-Dn, and BRSn-Avg compared with controls at V1 or V2; these changes occurred without differences in conventional markers of CV-ANS function (e.g., HF-HRV, LF-HRV, LF-SBP), HR, or SBP at either visit. CONCLUSIONS: Reduced BRS is a postconcussive consequence of CV-ANS dysfunction during the first postinjury week. Because SBP was similar between groups, it may be speculated that reduced BRS was not afferent in origin, but represents a postinjury consequence of the central nervous system after injury.