Journal Club

Journal Club Facilitator: Adrian Boltz

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Early Exercise is Associated with Faster Concussion Recovery Among Collegiate Athletes: Findings from the NCAA-DoD CARE Consortium

Authors: Landon B. Lempke, Elizabeth F. Teel, Robert C. Lynall, Nicole L. Hoffman, Thomas A. Buckley, James T. Eckner, Michael A. McCrea, Thomas W. McAllister, Steven P. Broglio, Julianne D. Schmidt, CARE Consortium Investigators

Abstract: 

• Background: Growing evidence indicates early exercise may improve symptoms and reduce clinical recovery time after concussion, but research examining collegiate student-athletes is scarce.
• Objective: The aim of this study was to compare symptom recovery time, clinical recovery time, and persisting post-concussion symptom (i.e., symptoms ≥ 28 days) prevalence by the timing of light exercise initiation before the graded return to play (RTP) protocol among concussed participants.
• Methods: Collegiate student-athletes (n = 1228; age 18.4 ± 0.9 years; 56.5% male, 76.3% division I; 33.7% ≥ 1 prior concussion) across 30 institutions enrolled in the CARE Consortium completed post-concussion assessments and were monitored over time. Symptom recovery (days from injury to symptom resolution) and clinical recovery (days from injury to return to play protocol completion) was determined by the student-athletes’ clinicians. Student-athletes were categorized by timing of light exercise initiation. Early (< 2 days post-concussion; n = 161), typical (3–7 days post-concussion; n = 281), and late exercise (≥ 8 days post-concussion; n = 169) groups were compared with the no-exercise group (n = 617; i.e., did not exercise prior to beginning the RTP protocol) for all analyses. Multivariable Cox regression models with hazard ratios (HR) and survival curves and a multivariable binomial regression model with prevalence ratios (PR) compared recovery outcomes between exercise groups while accounting for covariates.
• Results: Compared to the no-exercise group, the early exercise group was 92% more probable to experience symptom recovery (HR 1.92; 95% CI 1.57–2.36), 88% more probable to reach clinical recovery (HR 1.88; 95% CI 1.55–2.28) and took a median of 2.4 and 3.2 days less to recover, respectively. The late exercise group relative to the no-exercise group was 57% less probable to reach symptom recovery (HR 0.43; 95% CI 0.35–0.53), 46% less probable to achieve clinical recovery (HR 0.54; 95% CI 0.45–0.66) and took 5.3 days and 5.7 days more to recover, respectively. The typical exercise group did not differ in hazard for symptom or clinical recovery (p ≥ 0.329) compared with the no-exercise group. The prevalence of persisting post-concussion symptoms in the combined sample was 6.6%. Early exercise had 4% lower prevalence (PR 0.96, 95% CI 0.94–0.99) and typical exercise had 3% lower prevalence (PR 0.97, 95% CI 0.94–0.99) of persisting post-concussion symptoms, while the late exercise group had an elevated prevalence (PR 1.11, 95% CI 1.04–1.18) compared with the noexercise group.
• Conclusion: Exercise < 2 days post-concussion was associated with more probable and faster symptom and clinical recovery, and lower persisting post-concussion symptom prevalence. When considering our findings and existing literature, qualified clinicians may implement early exercise into their clinical practice to provide therapeutic treatment and improve student-athlete recovery.

Journal Club Facilitator: Reid Syrydiuk

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Lifetime Traumatic Brain Injury and Cognitive Domain Deficits in Late Life

Authors: Matthew J. Lennon, Helen Brooker, Byron Creese, Tony Thayanandan, Grant Rigney, Dag Aarsland, Adam Hampshire, Clive Ballard, Anne Corbett, Vanessa Raymont

Abstract: 

Traumatic brain injury (TBI) causes cognitive impairment but it remains contested regarding which cognitive domains are most affected. Further, moderate-severe TBI is known to be deleterious, but studies of mild TBI (mTBI) show a greater mix of negative and positive findings. This study examines the longer-term cognitive effects of TBI severity and number of mTBIs in later life. We examined a subset (n = 15,764) of the PROTECT study, a cohort assessing risk factors for cognitive decline (ages between 50 and 90 years). Participants completed cognitive assessments annually for 4 years. Cognitive tests were grouped using a principal components analysis (PCA) into working memory, episodic memory, attention, processing speed, and executive function. Lifetime TBI severity and number were retrospectively recalled by participants using the Brain Injury Screening Questionnaire (BISQ). Linear mixed models (LMMs) examined the effect of severity of head injury (non-TBI head strike, mTBI, and moderate-severe TBI) and number of mTBI at baseline and over time. mTBI was considered as a continuous and categorical variable (groups: 0 mTBI, 1 mTBI, 2 mTBIs, 3 mTBIs, and 4+ mTBIs). Of the participants 5725 (36.3%) reported at least one mTBI and 510 (3.2%) at least one moderate-severe TBI, whereas 3711 (23.5%) had suffered at worst a non-TBI head strike and 5818 (32.9%) reported no head injuries. The participants had suffered their last reported head injury an average (standard deviation, SD) of 29.6 (20.0) years prior to the study. Regarding outcomes, there was no worsening in longitudinal cognitive trajectories over the study duration but at baseline there were significant cognitive deficits associated with TBI. At baseline, compared with those without head injury, individuals reporting at least one moderate-severe TBI had significantly poorer attention (B = −0.163, p< 0.001), executive scores (B = −0.151, p = 0.004), and processing speed (B = −0.075, p = 0.033). Those who had suffered at least a single mTBI also demonstrated significantly poorer attention scores at baseline compared with the no head injury group (B = −0.052, p = 0.001). Compared with those with no mTBI, those in the 3 mTBI group manifested poorer baseline executive function (B = −0.149, p = 0.025) and attention scores (B = −0.085, p = 0.015). At baseline, those who had suffered four or more mTBIs demonstrated poorer attention (B = −0.135, p < 0.001), processing speed (B = −0.072, p = 0.009), and working memory (B = −0.052, p = 0.036), compared with those reporting no mTBI. TBI is associated with fixed, dose, and severity-dependent cognitive deficits. The most sensitive cognitive domains are attention and executive function, with approximately double the effect compared with processing speed and working memory. Post-TBI cognitive rehabilitation should be targeted appropriately to domain-specific effects. Significant long-term cognitive deficits were associated with three or more lifetime mTBIs, a critical consideration when counseling individuals post-TBI about continuing high-risk activities.

Journal Club Facilitator: Adrian Boltz

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Menstrual Cycle Patterns Following Concussion in Adolescent Patients

Authors: Patricia R. Roby, PhD, ATC; Adda Grimberg, MD; Christina L. Master, MD; Kristy B. Arbogast, PhD

Abstract: 

• Objective: To describe menstrual cycle patterns in concussed adolescents and investigate whether menstrual cycle phase at injury influenced post-concussion cycle pattern changes or concussion symptoms.
• Study Design: Data were collected prospectively from patients aged 13-18 years presenting to a specialty care concussion clinic for an initial visit (≤28 days post-concussion) and, if clinically indicated, at a follow-up visit 3-4 months post-injury. Primary outcomes included menstrual cycle pattern change since injury (change/no change), menstrual cycle phase at time of injury (calculated using date of last period before injury), and symptom endorsement and severity, measured by Post-Concussion Symptom Inventory (PCSI). Fisher’s exact tests were used to determine the association between menstrual phase at injury and change in cycle pattern. Multiple linear regression was used to determine if menstrual phase at injury was associated with PCSI endorsement and symptom severity, adjusting for age.
• Results: Five hundred and twelve post-menarchal adolescents were enrolled (age=15.2±1.4 years), with 111(21.7%) returning for follow-up at 3-4 months. Menstrual pattern change was reported by 4% of patients at initial visit and 10.8% of patients at follow-up. At 3-4 months, menstrual phase at injury was not associated with menstrual cycle changes (p=0.40) but was associated with endorsement of concussion symptoms on the PCSI (p=0.01).

Journal Club Facilitator: Reid Syrydiuk

Lead Author Joined the Discussion: Ali Al-Husseini

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Shorter Recovery Time in Concussed Elite Ice Hockey Players by Early Head-and-Neck Cooling: A Clinical Trial

Authors: Ali Al-Husseini, Mohammad Fazel Bakhsheshi, Anna Gard, Yelverton Tegner, and Niklas Marklund

Abstract:

A sports-related concussion (SRC) is most commonly sustained in contact sports, and is defined as a mild traumatic brain injury. An exercise-induced elevation of core body temperature is associated with increased brain temperature that may accelerate secondary injury processes following SRC, and exacerbate the brain injury. In a recent pilot study, acute head-neck cooling of 29 concussed ice hockey players resulted in shorter time to return-to-play. Here, we extended the clinical trial to include players of 19 male elite Swedish ice hockey teams over five seasons (2016-2021). In the intervention teams, acute head-neck cooling was implemented using a head cap for ‡45 min in addition to the standard SRC management used in controls.

The primary endpoint was time from SRC until return-to-play (RTP). Sixty-one SRCs were included in the intervention group and 71 SRCs in the control group. The number of previous SRCs was 2 (median and interquartile range [IQR]: 1.0-2.0) and 1 (IQR 1.0-2.0) in the intervention and control groups, respectively; p = 0.293. Median time to initiate head-neck cooling was 10 min (IQR 7-15; range 5-30 min) and median duration of cooling was 45 min (IQR 45-50; range 45-70 min). The median time to RTP was 9 days in the intervention group (IQR 7.0-13.5 days) and 13 days in the control group (IQR 9-30; p < 0.001).

The proportion of players out from play for more than the expected recovery time of 14 days was 24.7% in the intervention group, and 43.7% in controls (p < 0.05). Study limitations include that: 1) allocation to cooling or control management was at the discretion of the medical staff of each team, decided prior to each season, and not by strict randomization; 2) no sham cap was used and evaluations could not be performed by blinded assessors; and 3) it could not be established with certainty that injury severity was similar between groups.

While the results should thus be interpreted with caution, early head-neck cooling, with the aim of attenuating cerebral hyperthermia, may reduce post-SRC symptoms and lead to earlier return-to-play in elite ice hockey players.

Journal Club Facilitator: Adrian Boltz

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Neural Correlates of Sleep Recovery following Melatonin Treatment or Pediatric Concussion: A Randomized Controlled Trial

Authors: Kartik K. Iyer, Andrew Zalesky, Luca Cocchi and Karen M. Barlow

Abstract:

Evidence-based treatments for children with persistent post-concussion symptoms (PPCS) are few and limited. Common PPCS complaints such as sleep disturbance and fatigue could be ameliorated via the supplementation of melatonin, which has significant neuroprotective and anti-inflammatory properties. This study aims to identify neural correlates of melatonin treatment with changes in sleep disturbances and clinical recovery in a pediatric cohort with PPCS. We examined structural and functional neuroimaging (fMRI) in 62 children with PPCS in a randomized, double-blind, placebo-controlled trial of 3 mg or 10 mg of melatonin (NCT01874847). The primary outcome was the total youth self-report PostConcussion Symptom Inventory (PCSI) score after 28 days of treatment. Secondary outcomes included the change in the sleep domain PCSI score and sleep-wake behavior (assessed using wrist-worn actigraphy). Whole-brain analyses of (1) functional connectivity (FC) of resting-state fMRI, and (2) structural gray matter volumes via voxel-based morphometry were assessed immediately before and after melatonin treatment and compared with placebo to identify neural effects of melatonin treatment. Increased FC of posterior default mode network (DMN) regions with visual, somatosensory, and dorsal networks was detected in the melatonin groups over time. The FC increases also corresponded with reduced wake periods (r = -0.27, p = 0.01). Children who did not recover (n = 39) demonstrated significant FC increases within anterior DMN and limbic regions compared with those who did recover (i.e., PCSI scores returned to pre-injury level, n = 23) over time, ( p = 0.026). Increases in GM volume within the posterior cingulate cortex were found to correlate with reduced wakefulness after sleep onset (r = -0.32, p = 0.001) and sleep symptom improvement (r = 0.29, p = 0.02). Although the melatonin treatment trial was negative and did not result in PPCS recovery (with or without sleep problems), the relationship between melatonin and improvement in sleep parameters was linked to changes in function-structure within and between brain regions interacting with the DMN.