Publications

OBJECTIVES: To examine the network structure and relationships between common post-concussion symptoms and to apply network analysis to the Concussion Clinical Profiles Screening (CP Screen) in order to determine whether the CP Screen items cluster together within the appropriate predefined profiles.

STUDY DESIGN: Participants included 913 adolescents (mean age=15.04±1.60 years, 43.3% female) seen in a specialty clinic within 7.04±18.54 days of a diagnosed concussion. Participants completed the 29-item Concussion Clinical Profiles Screening (CP Screen) at their initial clinic visit, which were used to estimate networks and calculate centrality (strength, betweenness, expected influence) and bridge strength. Network stability was assessed via bootstrapped case-dropping procedures (1,000 iterations).

RESULTS: The most central symptoms were slow/wavy dizziness (vestibular; strength z-score=1.90), headache with cognitive exertion (cognitive/fatigue; strength z-score=1.50), eye strain (ocular; strength z-score=1.40), headache with light and noise (post-traumatic migraine; strength z-score=1.18), hyposomnia (sleep; strength z-score=1.02), and feeling more stressed than usual (mood/anxiety; strength z-score=0.89). Bridge analysis identified headache with cognitive exertion, difficulty in busy environments, post-traumatic migraine-related symptoms, and ocular-motor symptoms as key connectors across symptom clusters. Network stability was excellent (edge-weight correlation stability coefficient=0.75; strength correlation stability coefficient=0.67). Community analysis identified 4 communities: anxiety/mood, vestibular, ocular, and headache/migraine. Modularity was modest but indicative of meaningful community structure, and there was moderate agreement with the pre-defined clinical profiles.

CONCLUSIONS: Network analysis supported the CP Screen's original clinical profile structure. Findings also identified key central symptoms that may be driving elevated symptom burden post-concussion, as well as those symptoms that connect across profiles. This symptom profile approach may inform more effective, and targeted interventions for adolescents following concussion.

Mild traumatic brain injury (mTBI) is the most common type of traumatic brain injury (TBI), with 2.5 million cases reported annually in the United States. mTBI involves diverse signs, symptoms, and functional impairments that typically resolve within 1 month, but may persist. Female sex is one of the most consistent predictors associated with an increased risk of mTBI and worse outcomes, including greater symptom severity and prolonged recovery. Emerging evidence also suggests that females are at greater risk of menstrual cycle dysfunction following mTBI, which could have downstream consequences on reproductive and related women's health outcomes. Researchers have speculated that the underlying mechanism for these detrimental effects is the injury's impact on the hypothalamic-pituitary-ovarian (HPO) axis; however, it is necessary to further clarify the extent of these disruptions, identify consistent patterns across studies, and determine potential implications for reproductive health and hormonal regulation following mTBI. The goal of this narrative review is to understand the effects of mTBI on the HPO axis, identify gaps in the research and clinical practice, and provide recommendations to address these issues in females with mTBI. We summarize: (1) sex differences observed following mTBI, including physiological variables that contribute to these differences, particularly the menstrual and ovulatory cycles in females; (2) pituitary gland functions and hormonal regulations; (3) pituitary and hormonal dysfunction after mTBI; and (4) implications of hormone dysregulation on mTBI recovery. Our review concludes by highlighting methodological gaps, research needs, strategy recommendations, and treatment referrals for patients with HPO axis dysfunction after mTBI.

The aim of this study is to determine if there is a difference in tau and amyloid beta (Aβ) deposition on positron emission tomography (PET) scans between former players and controls, and if there is a differential association of the tau and Aβ deposition with concussion symptom burden. Participants completed the Rivermead Post-Concussion Questionnaire (RPQ) and PET imaging using Pittsburgh Compound B (PiB) and AV1451 ligands to identify uptake of Aβ and tau, respectively. Aβ standardized uptake value ratios (SUVR) and tau SUVR were compared between players and controls using a general linear model including age, race/ethnicity, years of education completed, and total number of prior sport-related traumatic brain injuries (TBIs) as covariates. A series of linear regression models were built to predict RPQ symptom scores including group status (player vs. control), Aβ SUVR and tau SUVR, and the interaction between group status and the Aβ SUVR and tau SUVR. Former players reported 4.9 ± 2.8 and control reported 1.4 ± 1.6 prior sport-related TBIs. Neither group reported any non-sport-related TBIs. Former players had higher RPQ symptom scores (13.3 ± 1.8) compared with controls (4.7 ± 1.8; p = 0.003). Controls had higher uptake for Aβ in the precuneus (1.22 ± 0.02) compared to players (1.14 ± 0.02; corrected p = 0.007). There were no differences between groups in uptake for Aβ in any other region of interest or tau in any region of interest. None of the regression models associating the interaction of group status and uptake with RPQ symptoms were significant. Aβ and tau PET scans may have limited utility for identifying potential neuropathological differences between participants with a career in professional football from controls who did not play football beyond high school. The PET tracer used for tau in the current study (AV1451) is well-suited for Alzheimer's disease-related tau pathology with limited binding for chronic traumatic encephalopathy-type tau proteins. A PET tracer for chronic traumatic encephalopathy-related tau deposition should remain a focus of future research.

IMPORTANCE: Mild traumatic brain injuries (mTBI) involving anxiety and mood, cognitive, migraine and headache, ocular, vestibular, sleep, and autonomic domains can result in chronic symptoms and impairments, thereby increasing morbidity and decreasing quality of life for patients. Timely interventions targeting involved mTBI domains may improve symptoms and impairments and accelerate recovery.

OBJECTIVE: To evaluate the effectiveness of a targeted multidomain (T-MD) intervention for mTBI in adults.

DESIGN, SETTING, AND PARTICIPANTS: This multisite randomized clinical trial (RCT), conducted at 2 specialty concussion clinics from June 2021 to April 2024, involved a 4-week intervention and a total follow-up duration of 3 months. Participants were aged 18 to 49 years and were within 8 days to 6 months of an mTBI.

INTERVENTION: Patients were randomized to T-MD interventions tailored to each domain or a behavioral management control group (control).

MAIN OUTCOMES AND MEASURES: Primary outcomes included changes in the Neurobehavioral Symptom Inventory (NSI) and Patient Global Impression of Change (PGIC) assessed from baseline to 4 weeks. Secondary outcomes included domain-specific symptoms and impairments and adverse events. Least-squares adjusted mean differences (aMDs) and 95% CIs were calculated to assess differences between groups.

RESULTS: Of 1639 patients screened, 745 were eligible and 162 (81 per group) were randomized to T-MD or control (102 female [63%]; 60 male [37%]; mean [SD] age, 29 [8] years). The 2 groups experienced similar improvements over time in NSI symptom severity (aMD, -0.5; 95% CI, -3.6 to 2.6; P = .98) and perceived improvement on the PGIC (odds ratio, 1.18; 95% CI, 0.46-3.04; P = .21). In sensitivity analyses, the T-MD group experienced greater improvement in total (aMD, -4.0; 95% CI, -7.6 to -0.5; P = .045), ocular (aMD, -0.9; 95% CI, -1.7 to -0.1; P = .02), and vestibular (aMD, -0.8; 95% CI, -1.5 to -0.2; P = .01) symptoms; vestibular and ocular motor convergence (aMD, -1.8; 95% CI, -3.2 to -0.3; P = .046); horizontal vestibulo-ocular reflex (aMD, -1.8; 95% CI, -3.2 to -0.3; P = .02); vertical vestibulo-ocular reflex (aMD, -2.2; 95% CI, -3.8 to -0.7; P = .01); visual motion sensitivity (aMD, -2.2; 95% CI, -4.0 to -0.7; P = .01); and cognitive processing speed (aMD, 2.4; 95% CI, 0.6 to 4.2; P = .04). Adverse events were reported by 10 participants (6%).

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, mTBI symptoms and patients' perception of change improved similarly for the T-MD and control groups. These findings can inform a more effective, efficient, and evidence-based approach to care for mTBI.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04549532.

BACKGROUND: We aimed to compare physiological responses, concussion symptoms, and rating of perceived exertion between the 10-M and treadmill protocols for the aerobic component of the dynamic exertion test (EXiT). We hypothesized that these outcomes would be similar between protocols and have moderate-to-strong agreement.

METHODS: We conducted a within subject, cross-over study design comprised of fourteen healthy and physically active male adults. Participants performed the treadmill and the 10-M protocols in a randomized order separated by a 30-minute rest period. Pre- and postexercise resting heart rate (HR), and systolic and diastolic blood pressure (BP) were measured. Symptoms (headache, dizziness, and nausea), and RPE were recorded. Intraclass correlation coefficients (ICCs) were conducted for HR and BP, and Cronbach's alpha for symptoms and RPE.

RESULTS: There was moderate agreement for HR across minutes 6-12 (ICC>0.723, P<0.002) and postexercise diastolic BP (ICC=0.776, P<0.022), but not postexercise systolic BP or resting HR (P>0.05). Concussion symptoms and RPE were equivocal (Cronbach's alpha = 0.955, P<0.001).

CONCLUSIONS: Physiological and clinical responses between 10-M and treadmill conditions for the aerobic component of EXiT were comparable; the 10-M protocol may be an alternative approach to implement the aerobic component of EXiT.

Uncovering objective biomarkers of mild traumatic brain injury (mTBI) may lead to earlier and more accurate identification of this injury, improved prognostic assessment and earlier targeted treatments. Emerging evidence highlights the potential of salivary biomarkers, particularly proteins, as a noninvasive, inexpensive and objective method for diagnosing mTBI, due to their presence in saliva following blood-brain barrier disruption; however, consensus on their utility remains limited. Our aim was to explore the diagnostic potential of salivary protein biomarkers in the identification of mTBI. A comprehensive search was conducted from April to September 2024 across the PubMed, Embase and Google Scholar databases. Original observational studies examining the diagnostic utility of salivary protein biomarkers for mTBI in human populations were included. Seven (1.7%) studies out of 411 identified reports met the inclusion criteria. A total of 49 salivary proteins demonstrated significant differential expression. Subgroup analysis based on the mechanism of injury (sports-related and non-sports-related) identified 4 overlapping proteins: ALOX5, ITGB2, ADRB2, and HRH1. ALOX5 and ITGB2 were significantly upregulated in both subgroups, while ADRB2 and HRH1 were downregulated in sports-related cases and upregulated in non-sports-related cases, which may reflect differential expression related to the region of impact and progression of injury pathophysiology. These findings suggest that salivary proteins such as ALOX5, ITGB2, ADRB2, and HRH1 may serve as promising noninvasive biomarkers for the diagnosis of mTBI. Their involvement in key processes in mTBI pathology supports further investigation in larger, rigorously designed clinical studies to validate their diagnostic utility.

OBJECTIVE: To determine the agreement of parent and child responses to the Brain Injury Perception Scale (BIPS), a modified version of the Illness Perceptions Questionnaire-Revised, following a pediatric concussion.

METHOD: This was a cross-sectional study of 88 parent-child dyads who completed the BIPS at their initial visit to a specialty concussion clinic within 30 days following pediatric (11-18 years of age) concussion. Descriptive statistics were calculated, followed by Spearman's rho (ρ), which assessed parent-child item consistency. Cross-tab tables were used to understand the direction of item consistency.

RESULTS: Only five (13.2%) out of 38 BIPS items demonstrated parent-child consistency (p < .05), with both disagreeing that the brain injury is permanent (ρ = .27), will have major consequences on their life (ρ = .25), makes them upset (ρ = .22), will strongly affect the way others see them (ρ = .29), and will be with them for the rest of their life (ρ = .22).

CONCLUSIONS: Parent-child agreement regarding brain injury perceptions following a pediatric concussion was low (13%), reflecting the importance of assessing and then addressing parent and child perceptions individually in pediatric concussion management.

BACKGROUND AND PURPOSE: To evaluate the effect of intensity and frequency of vestibular rehabilitation exercises over time on dizziness handicap and secondary outcomes in adults with vestibular impairments following mild traumatic brain injuries (mTBI).

METHODS: The Targeted Rehabilitation Exercises for Vestibular (T-REV) impaiments randomized clinical trial was conducted from February 2020 to May 2024. Adult (18-50 years) civilian and military service members within 8 days to 1 year of mTBI with vestibular impairments participated. The sample size target was 252 participants. Exercises prescribed by a physical therapist were performed at home for 4 weeks at an intensity of 30% or 70%, and a frequency of once or twice daily. The Dizziness Handicap Inventory (DHI) and secondary outcomes were assessed at baseline, 2 and 4 weeks, and DHI at 12 weeks. Least square mean differences and 95% confidence intervals were calculated from a linear mixed model to examine the effects of intensity, frequency, time, and their interactions.

RESULTS: A total of 120 participants completed baseline assessment (69 F, 51 M; 73 civilians, 47 military service members; mean (SD) age: 29 (9) years). Group differences in DHI and secondary outcomes over time due to intensity or frequency were equivocal. For all participants, mean improvement in DHI from baseline to 4 weeks was 16 points (95% CI: 13-19 points, P < .0001), and most secondary outcomes significantly improved across 4 weeks. Adverse events occurred in 20% of the participants.

DISCUSSION AND CONCLUSIONS: The dose of vestibular rehabilitation for individuals with mTBI-related vestibular impairments can be individualized based on patient goals and symptom burden.

BACKGROUND: Field-based contact sports, including American football and rugby are among those with the highest sport-related concussion (SRC) rates. Regarding SRC treatment, gradual return-to-play (RTP) protocols are commonly used, however variability in RTP protocols between sporting bodies and scholastic institutions makes accurately interpreting published SRC severity data difficult.

AIMS: Compare SRC recovery times, RTP protocols, and mandated sit-out period duration among adult amateur contact field sports.

METHODS: MEDLINE, CINAHL Complete, SPORTDiscus, APA PsycInfo, and APA PsycArticles were searched on May 13th, 2024. Eligibility criteria included (1) published in English in a peer-reviewed journal from 2015 to 2024, (2) adult population, (3) amateur, field-based contact sport athlete population, (4) diagnosed and/or suspected SRC, and (5) recovery time (days/weeks) data available.

RESULTS: 19/6085 (< 1%) studies comprising 58 datasets met all inclusion criteria. The studies comprised American football (10/19, 52.6%), field-hockey (5/19, 26.3%), lacrosse (9/19, 47.4%), ladies gaelic football (1/19, 5.3%), rugby (8/19, 42.1%), soccer (10/19, 52.6%), and sprint football (1/19, 5.2%). Mandated sit-out periods ranged from 0 to 21 days across sports, and RTP protocol durations ranged from 5 to 21 days. The most common RTP protocol duration was 7 days (n = 31/58), and mandated sit-out period was no same-day return (n = 25/58). Field hockey had the longest reported SRC recovery duration (34 days), and rugby had the longest mandated sit-out period (21 days).

CONCLUSION: Recovery time following concussion in contact sports should be interpreted in light of sport type, mandated sit-out policies, and RTP protocols. Empirical evidence should drive decisions in RTP protocols and sit-out periods, which are currently inconsistent between sports.