Journal Club

Journal Club Facilitator: Reid Syrydiuk

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Cavum Septum Pellucidum in Former American Football Players Findings From the DIAGNOSE CTE Research Project

Authors: Hector Arciniega, Leonard B Jung, Fatima Tuz-Zahra, Yorghos Tripodis, Omar John, Nicholas Kim, Holly W Carrington, Evdokiya E Knyazhanskaya, Arushi Chamaria, Katherine Breedlove, Tim L Wiegand, Daniel Daneshvar,  Tashrif Billah , Ofer Pasternak, Michael J Coleman, Charles H Adler, Charles Bernick, Laura J Balcer, Michael L Alosco, Alexander P Lin, Inga K Koerte, Jeffrey L Cummings, Eric M Reiman, Robert A Stern, Sylvain Bouix, Martha E Shenton; DIAGNOSE CTE Research Project

Objective: Exposure to repetitive head impacts (RHI) is linked to the development of chronic traumatic encephalopathy (CTE), which can only be diagnosed at post-mortem. The presence of a cavum septum pellucidum (CSP) is a common finding in post-mortem studies of confirmed CTE and in neuroimaging studies of individuals exposed to RHI. This study examines CSP in living former American football players, investigating its association with RHI exposure, traumatic encephalopathy syndrome (TES) diagnosis, and provisional levels of certainty for CTE pathology.

Methods: Data from the DIAGNOSE CTE Research Project were used to compare the presence and ratio of CSP in former American football players (n = 175), consisting of former college (n = 58) and former professional players (n = 117), and asymptomatic unexposed controls without RHI exposure (n = 55). We further evaluated potential associations between CSP measures and cumulative head impact index (CHII) measures (frequency, linear acceleration, and rotational force), a TES diagnosis (yes/no), and a provisional level of certainty for CTE pathology (suggestive, possible, and probable).

Results: Former American football players exhibited a higher CSP presence and ratio than unexposed asymptomatic controls. Among player subgroups, professional players showed a greater CSP ratio than former college players and unexposed asymptomatic controls. Among all football players, CHII rotational forces correlated with an increased CSP ratio. No significant associations were found between CSP measures and diagnosis of TES or provisional levels of certainty for CTE pathology.

Discussion: This study confirms previous findings, highlighting a greater prevalence of CSP and a greater CSP ratio in former American football players compared with unexposed asymptomatic controls. In addition, former professional players showed a greater CSP ratio than college players. Moreover, the relationship between estimates of CHII rotational forces and CSP measures suggests that cumulative frequency and strength of rotational forces experienced in football are associated with CSP. However, CSP does not directly correlate with TES diagnosis or provisional levels of certainty for CTE, indicating that it may be a consequence of RHI associated with rotational forces. Further research, especially longitudinal studies, is needed for confirmation and to explore changes over time.

Journal Club Facilitator: Reid Syrydiuk

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Examining the role of depression on the relationship between performance-based and self-reported cognitive functioning after sport-related concussion

Authors: McKenna S. Sakamoto, Garrett A. Thomas, Megan I. Bradson, Peter A. Arnett

Objective: Little is known about the relationship between neuropsychological test performance, cognitive symptom reporting, and depressive symptoms after sport-related concussion. Accordingly, this cross- sectional study examined these relations in collegiate athletes. It was hypothesized that depressive symptoms would moderate and mediate the relationship between performance-based and self- reported cognitive functioning after concussion.

Methods: After sustaining a sport-related concussion, 110 collegiate athletes completed a neuropsychological battery, the Post-Concussion Symptoms Scale, and the Beck Depression Inventory-Fast Screen. Neuropsychological test performance, depressive symptoms, and their interactions were entered into distinct hierarchical linear regression analyses with self-reported cognition as the dependent variable to assess moderation. Mediation was analyzed using the PROCESS macro with 500 bootstrap samples and a 95% confidence interval.

Results: There was significant interaction between the mean memory composite and depressive symptoms when predicting cognitive symptom reporting, p=0.047. Simple effects tests revealed that for the athletes who had a lower memory composite score, an increase in depressive symptom lead to an increase in self-reported cognitive dysfunction, p< 0.001, ηp 2=0.11. Depressive symptoms partially mediated the relationship between the memory composite and cognitive symptom reporting, indirect effect = -0.26,95%CI[−0.58,0.001], but this relationship was not found for any other neurocognitive domain.

Conclusions: For tests of memory, depressive symptoms moderated and partially mediated the relationship between performance-based and self-reported cognitive functioning after sport-related concussion. Athletes report high depressive symptoms and cognitive dysfunction may need more comprehensive evaluations to inform return-to-play decisions, and depression could be a treatment targe for athletes who report high levels of cognitive dysfunction after concussion.

Journal Club Facilitator: Adrian Boltz

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Mild Traumatic Brain Injury and Career Stage Associate with Visible Perivascular Spaces in Special Operations Forces Soldiers

Authors: Powell, Jacob R ; Zong, Xiaopeng ; Weinstein, Joshua M ; DeLellis, Stephen M ; Kane, Shawn F ; Means, Gary E ; Mihalik, Jason P.

Abstract: Mild traumatic brain injury (mTBI) and occupational blast exposure in military Service Members may lead to impaired brain waste clearance which increases neurological disease risk. Perivascular spaces (PVS) are a key part of the glymphatic system which supports brain waste clearance, preferentially during sleep. Visible PVS on clinical magnetic resonance imaging have been previously observed in patients with neurodegenerative diseases and animal neurotrauma models. The purpose of this study was to determine associations between PVS morphological characteristics, military career stage, and mTBI history in Special Operations Forces (SOF) Soldiers.

Background and objectives: The overall study purpose was to quantify dilated PVS using a novel fully convolutional neural network and determine the association between PVS burden (number and volume) and mTBI history in SOF combat Soldiers. Our specific aims were twofold: (1) To describe the differences in PVS burden (number and volume) between SOF members with and without mTBI history and (2) describe the differences in PVS burden (number and volume) between Soldiers at the start of their SOF career (baseline) and during their SOF career (in-career).

Results: In total, 223 healthy SOF combat Soldiers (age = 33.1 ± 4.3yrs) were included, 217 reported career stage. Soldiers with mTBI history had greater PVS number (z = 2.51, P = 0.013) and PVS volume (z = 2.42, P = 0.016). In-career SOF combat Soldiers had greater PVS number (z = 2.56, P = 0.01) and PVS volume (z = 2.28, P = 0.02) compared to a baseline cohort.

Conclusion: Mild TBI history is associated with increased PVS burden in SOF combat Soldiers that are clinically recovered from mTBI. This may indicate ongoing physiological changes that could lead to impaired waste clearance via the glymphatic system. Future studies should determine if PVS number and volume are meaningful neurobiological outcomes for neurodegenerative disease risk and if clinical interventions such as improving sleep can reduce PVS burden.

Journal Club Facilitator: Adrian Boltz

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Flortaucipir tau PET findings from former professional and college American football players in the DIAGNOSE CTE research project

Authors: Su, Yi; Protas, Hillary; Luo, Ji; Chen, Kewei; Alosco, Michael L; Adler, Charles H; Balcer, Laura J; Bernick, Charles; Au, Rhoda; Banks, Sarah J; Barr, William B; Coleman, Michael J; Dodick, David W; Katz, Douglas I; Marek, Kenneth L; McClean, Michael D; McKee, Ann C; Mez, Jesse; Daneshvar, Daniel H; Palmisano, Joseph N; Peskind, Elaine R; Turner, 2nd, Robert W; Wethe, Jennifer V; Rabinovici, Gil; Johnson, Keith; Tripodis, Yorghos; Cummings, Jeffrey L; Shenton, Martha E; Stern, Robert A; Reiman, Eric M

Abstract: Tau is a key pathology in chronic traumatic encephalopathy (CTE). Here, we report our findings in tau positron emission tomography (PET) measurements from the DIAGNOSE CTE Research Project.

Methods: We compare flortaucipir PET measures from 104 former professional players (PRO), 58 former college football players (COL), and 56 same‐age men without exposure to repetitive head impacts (RHI) or traumatic brain injury (unexposed [UE]); characterize their associations with RHI exposure; and compare players who did or did not meet diagnostic criteria for traumatic encephalopathy syndrome (TES).

Results: Significantly elevated flortaucipir uptake was observed in former football players (PRO+COL) in prespecified regions ( p < 0.05). Association between regional flortaucipir uptake and estimated cumulative head impact exposure was only observed in the superior frontal region in former players over 60 years old. Flortaucipir PET was not able to differentiate TES groups.

Discussion:Additional studies are needed to further understand tau pathology in CTE and other individuals with a history of RHI.

Journal Club Facilitator: Dr. Mark Roberts

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Associations Between Traumatic Brain Injury and Cognitive Decline Among Older Veteran Men – A Twin Study

Authors: Chanti-Ketterl, Marianne; Pieper, Carl F; Yaffe, Kristine; Plassman, Brenda L

Abstract: Traumatic brain injuries (TBIs) are associated with increased risk of dementia, but whether lifetime TBI influences cognitive trajectories in later life is less clear. Cognitive interventions after TBI may improve cognitive trajectories and delay dementia. Because twins share many genes and environmental factors, we capitalize on the twin study design to examine the association between lifetime TBI and cognitive decline.

Methods: Participants were members of the National Academy of Sciences-National Research Council’s Twin Registry of male veterans of World War II with self or proxy-reported history of TBI and with up to 4 observations over 12 years of the modified Telephone Interview for Cognitive Status (TICS-m). We used linear random-effects mixed models to analyze the association between TBI and TICS-m in the full sample and among co-twins discordant for TBI. Additional TBI predictor variables included number of TBIs, severity (loss of consciousness [LOC]), and age of first TBI (age <25 vs 25+ years [older age TBI]). Models were adjusted for age (centered at 70 years), age-squared, education, wave, twin pair, lifestyle behaviors, and medical conditions.

Results: Of 8,662 participants, 25% reported TBI. History of any TBI (β = −0.56, 95% CI −0.73 to −0.39), TBI with LOC (β = −0.51, 95% CI −0.71 to −0.31), and older age TBI (β = −0.66, 95% CI −0.90 to −0.42) were associated with lower TICS-m scores at 70 years. TBI with LOC (β = −0.03, 95% CI −0.05 to −0.001), more than one TBI (β = −0.05, 95% CI −0.09 to −0.002,), and older age TBI (β = −0.06, 95% CI −0.09 to −0.03) were associated with faster cognitive decline. Among monozygotic pairs discordant for TBI (589 pairs), history of any TBI (β = −0.55, 95% CI −0.91 to −0.19) and older age TBI (β = −0.74, 95% CI −1.22 to −0.26) were associated with lower TICS-m scores at 70 years. Those with more than one TBI (β = −0.13, 95% CI −0.23 to −0.03) and older age TBI (β = −0.07, 95% CI −0.13 to −0.002) showed greater cognitive decline compared with their co-twin without TBI.

Conclusion: These findings support an association of the effect of TBI on cognitive score and the rapidity of cognitive decline in later life. The results in monozygotic pairs, who share all genes and many exposures, particularly in early life, provide additional evidence of a causal relationship between TBI and poorer late-life cognitive outcomes.

Journal Club Facilitator: Reid Syrydiuk

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Psychosocial Factors Associated With Time to Recovery After Concussion in Adolescent Ice Hockey Players

Authors: Luszawski, Caroline A. MSc, Plourde, Vickie Ph.D., Sick, Stacy R. BSc, CAT(C), Galarneau, Jean-Michel Ph.D., Eliason, Paul H. Ph.D., Brooks, Brian L. Ph.D., Mrazik, Martin Ph.D., Debert, Chantel T. MD, MSc, Lebrun, Constance MDCM, Babul, Shelina Ph.D., Hagel, Brent E. Ph.D., Dukelow, Sean P. MD, Ph.D., Schneider, Kathryn J. Ph.D., Emery, Carolyn A. Ph.D., Yeates, Keith Owen Ph.D.

Abstract: 

Background and objectives: To investigate the association between psychosocial factors and physician clearance to return to play (RTP) in youth ice hockey players after sport-related concussion.

Design: Prospective cohort study, Safe to Play (2013-2018).

Setting: Youth hockey leagues in Alberta and British Columbia, Canada.

Participants: Three hundred fifty-three ice hockey players (aged 11-18 years) who sustained a total of 397 physician-diagnosed concussions.

Independent Variables: Psychosocial variables.

Main Outcome Measures: Players and parents completed psychosocial questionnaires preinjury. Players with a suspected concussion were referred for a study physician visit, during which they completed the Sport Concussion Assessment Tool (SCAT3/SCAT5) and single question ratings of distress and expectations of recovery. Time to recovery (TTR) was measured as days between concussion and physician clearance to RTP. Accelerated failure time models estimated the association of psychosocial factors with TTR, summarized with time ratios (TRs). Covariates included age, sex, body checking policy, days from concussion to the initial physician visit, and symptom severity at the initial physician visit.

Results: Self-report of increased peer-related problems on the Strengths and Difficulties Questionnaire (TR, 1.10 [95% CI, 1.02-1.19]), higher ratings of distress about concussion outcomes by participants (TR, 1.06 [95% CI, 1.01-1.11]) and parents (TR, 1.05 [95% CI, 1.01-1.09]), and higher parent ratings of distress about their child’s well-being at the time of injury (TR, 1.06 [95% CI, 1.02-1.09]) were associated with longer recovery.

Conclusions: Greater pre-existing peer-related problems and acute distress about concussion outcomes and youth well-being predicted longer TTR. Treatment targeting these psychosocial factors after concussion may promote recovery.

Journal Club Facilitator: Dr. Mark Roberts

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Longitudinal Changes in Regional Brain Volumes and Cognition of Professional Fighters With Traumatic Encephalopathy Syndrome

Authors: Brooke D Conway Kleven, Lung-Chang Chien, Brian Labus, Chad L Cross, Aaron Ritter, Rebekah Randall, Arturo Montes, Charles bernick

Abstract: 

• Due to current limitations in diagnosing chronic traumatic encephalopathy (CTE) clinically, traumatic encephalopathy syndrome (TES) has been proposed as the clinical presentation of suspected CTE. This study aimed to determine whether there was an association between a clinical diagnosis of TES and subsequent temporal decline in cognitive or MRI volumetric measures.
• This was a secondary analysis of the Professional Athletes Brain Health Study (PABHS), inclusive of active and retired professional fighters older than 34 years. All athletes were adjudicated as TES positive (TES+) or TES negative (TES−) based on the 2021 clinical criteria. General linear mixed models were used to compare MRI regional brain volumes and cognitive performance between groups.
• A total of 130 fighters met inclusion criteria for consensus conference. Of them, 52 fighters (40%) were adjudicated as TES+. Athletes with a TES+ diagnosis were older and had significantly lower education. Statistically significant interactions and between-group total mean differences were found in all MRI volumetric measurements among the TES+ group compared with those among the TES− group. The rate of volumetric change indicated a significantly greater increase for lateral (estimate = 5,196.65; 95% CI = 2642.65, 7750.66) and inferior lateral ventricles (estimate = 354.28; 95% CI = 159.90, 548.66) and a decrease for the hippocampus (estimate = −385.04, 95% CI = −580.47, −189.62), subcortical gray matter (estimate = −4,641.08; 95% CI = −6783.98, −2498.18), total gray matter (estimate = −26492.00; 95% CI = −50402.00, −2582.32), and posterior corpus callosum (estimate = −147.98; 95% CI = −222.33, −73.62). Likewise, the rate of cognitive decline was significantly greater for reaction time (estimate = 56.31; 95% CI = 26.17, 86.45) and other standardized cognitive scores in the TES+ group.
• The 2021 TES criteria clearly distinguishes group differences in the longitudinal presentation of volumetric loss in select brain regions and cognitive decline among professional fighters 35 years and older. This study suggests that a TES diagnosis may be useful in professional sports beyond football, such as boxing and mixed martial arts. These findings further suggest that the application of TES criteria may be valuable clinically in predicting cognitive decline.

Journal Club Facilitator: Dr. Steven Broglio

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Beyond acute concussion assessment to office management: a systematic review informing the development of a Sport Concussion Office Assessment Tool (SCOAT6) for adults and children

Authors: Jon S Patricios, Kathryn J Schneider, Jiri Dvorak, Osman Hassan Ahmed, Cheri Blauwet, Robert C Cantu, Gavin A Davis, Ruben J Echemendia, Michael Makdissi, Michael McNamee, Steven Broglio, Carolyn A Emery, Nina Feddermann-Demont, Gordon Ward Fuller, Christopher C Giza, Keven M Guskiewicz, Brian Hainline, Grant L Iverson, Jeffrey S Kutcher, John J Leddy, David Maddocks, Geoff Manley, Michael McCrea, Laura K Purcell, Margot Putukian, Haruhiko Sato, Markku P Tuominen, Michael Turner, Keith Owen Yeates, Stanley A Herring, Willem Meeuwisse

Abstract: 

For over two decades, the Concussion in Sport Group has held meetings and developed five international statements on concussion in sport. This 6th statement summarises the processes and outcomes of the 6th International Conference on Concussion in Sport held in Amsterdam on 27–30 October 2022 and should be read in conjunction with the (1) methodology paper that outlines the consensus process in detail and (2) 10 systematic reviews that informed the conference outcomes. Over 3½ years, author groups conducted systematic reviews of predetermined priority topics relevant to concussion in sport. The format of the conference, expert panel meetings and workshops to revise or develop new clinical assessment tools, as described in the methodology paper, evolved from previous consensus meetings with several new components. Apart from this consensus statement, the conference process yielded revised tools including the Concussion Recognition Tool-6 (CRT6) and Sport Concussion Assessment Tool-6 (SCAT6, Child SCAT6), as well as a new tool, the Sport Concussion Office Assessment Tool-6 (SCOAT6, Child SCOAT6). This consensus process also integrated new features including a focus on the para athlete, the athlete’s perspective, concussion-specific medical ethics and matters related to both athlete retirement and the potential long-term effects of SRC, including neurodegenerative disease. This statement summarises evidence-informed principles of concussion prevention, assessment and management, and emphasises those areas requiring more research.

Journal Club Facilitator: Mark Roberts

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Beyond acute concussion assessment to office management: a systematic review informing the development of a Sport Concussion Office Assessment Tool (SCOAT6) for adults and children

Authors: Jon S Patricios , Geoff M Schneider, Jacqueline van Ierssel , Laura K Purcell, Gavin A Davis , Ruben J Echemendia , Pierre Fremont , Gordon Ward Fuller , Stanley A Herring, Kimberly G Harmon , Kirsten Holte, Mike Loosemore , Michael Makdissi, Michael McCrea , William P Meehan, III, Patrick O’Halloran , Zahra Premji , Margot Putukian , Isla Jordan Shill , Michael Turner , Kenzie Vaandering , Nick Webborn , Keith Owen Yeates , Kathryn J Schneider

Abstract: 

• Objectives To systematically review the scientific literature regarding the assessment of sport- related concussion (SRC) in the subacute phase (3–30 days) and provide recommendations for developing a Sport Concussion Office Assessment Tool (SCOAT6). Data sources MEDLINE, Embase, PsycINFO, Cochrane CENTRAL, CINAHL, SPORTDiscus and Web of Science searched from 2001 to 2022. Data extracted included study design, population, definition of SRC diagnosis, outcome measure(s) and results. Eligibility criteria (1) Original research, cohort studies, case–control studies, diagnostic accuracy and case series with samples >10; (2) SRC; (3) screening/technology that assessed SRC in the subacute period and (4) low risk of bias (ROB). ROB was performed using adapted Scottish Intercollegiate Guidelines Network criteria. Quality of evidence was evaluated using the Strength of Recommendation Taxonomy classification. Results Of 9913 studies screened, 127 met inclusion, assessing 12 overlapping domains. Results were summarised narratively. Studies of acceptable (81) or high (2) quality were used to inform the SCOAT6, finding sufficient evidence for including the assessment of autonomic function, dual gait, vestibular ocular motor screening (VOMS) and mental health screening. Conclusion Current SRC tools have limited utility beyond 72 hours. Incorporation of a multimodal clinical assessment in the subacute phase of SRC may include symptom evaluation, orthostatic hypotension screen, verbal neurocognitive tests, cervical spine evaluation, neurological screen, Modified Balance Error Scoring System, single/dual task tandem gait, modified VOMS and provocative exercise tests. Screens for sleep disturbance, anxiety and depression are recommended. Studies to evaluate the psychometric properties, clinical feasibility in different environments and time frames are needed.

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.