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Traumatic brain injury (TBI) is considered to initiate cerebrovascular pathology, involving in the development of multiple forms of neurodegeneration. However, it is unknown the relationships between imaging marker of cerebrovascular injury (white matter hyperintensity, WMH), its load on white matter tract and disrupted brain dynamics with cognitive function in mild TBI (mTBI). MRI data and neuropsychological assessments were collected from 85 mTBI patients and 52 healthy controls. Between-group difference was conducted for the tract-specific WMH volumes, white matter integrity, and dynamic brain connectivity (i.e., fractional occupancies [%], dwell times [seconds], and state transitions). Regression analysis was used to examine associations between white matter damage, brain dynamics, and cognitive function. Increased WMH volumes induced by mTBI within the thalamic radiation and corpus callosum were highest among all tract fibers, and related with altered fractional anisotropy (FA) within the same tracts. Clustering identified two brain states, segregated state characterized by the sparse inter-independent component connections, and default mode network (DMN)-centered integrated state with strongly internetwork connections between DMN and other networks. In mTBI, higher WMH loads contributed to the longer dwell time and larger fractional occupancies in DMN-centered integrated state. Every 1 mL increase in WMH volume within the left thalamic radiation was associated with a 47% increase fractional occupancies, and contributed to 65.6 s delay in completion of cognitive processing speed test. Our study provided the first evidence for the structural determinants (i.e., small vessel lesions) that mediate the spatiotemporal brain dynamics to cognitive impairments in mTBI., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

Background: The mechanisms of a concussion place stress on the cervical spine like that of a whiplash event, which can result in cervical spine dysfunction. This study aimed to determine if underlying cervical spine mobility and sensorimotor function deficits occur in individuals who are post-concussion with near resolution of symptoms., Methods: Twenty-five participants with a self-reported concussive event within a year (PC group: post-concussion 157  +  120 d, 9 men, age: 25 ± 8 yr) and 26 comparable peers (Peer group, 9 men, age: 25 ± 7 yr) were tested. The Post-Concussion Symptom Scale (PCSS) quantified residual concussion symptoms. Participants completed cervical joint position error (JPE) and cervical spine joint mobility tests blinded from each other. Group mean differences were analyzed using t-tests., Results: The PC group had minimal symptoms (PCSS = 6.8 ± 6.5) but substantial differences in JPE tests compared to the Peer group (PC = 7.4 ± 1.8 cm; PG = 5.6 ± 1.1 cm; p  < .001). Those PC participants with pain during joint testing ( n  = 15) had worse JPE (Painful = 8.1 ± 1.8 cm, No-pain = 6.3 ± 1.6 cm; p  = .02) and less averaged lower cervical spine joint mobility compared to PC participants without pain (Painful = 0.66 ± 0.22, No-pain = 0.87 ± 0.19; p  = .02, Normal motion = 1.0)., Conclusion: Following a concussion, it is a reasonable recommendation to screen the cervical spine to identify impairments in joint mobility and JPE that contribute to neck dysfunction.

The complex pathology of mild traumatic brain injury (mTBI) is a main contributor to the difficulties in achieving a successful therapeutic regimen. Thyroxine (T4) administration has been shown to prevent the cognitive impairments induced by mTBI in mice but the mechanism is poorly understood. To understand the underlying mechanism, we carried out a single cell transcriptomic study to investigate the spatiotemporal effects of T4 on individual cell types in the hippocampus and frontal cortex at three post-injury stages in a mouse model of mTBI. We found that T4 treatment altered the proportions and transcriptomes of numerous cell types across tissues and timepoints, particularly oligodendrocytes, astrocytes, and microglia, which are crucial for injury repair. T4 also reversed the expression of mTBI-affected genes such as Ttr, mt-Rnr2, Ggn12, Malat1, Gnaq, and Myo3a, as well as numerous pathways such as cell/energy/iron metabolism, immune response, nervous system, and cytoskeleton-related pathways. Cell-type specific network modeling revealed that T4 mitigated select mTBI-perturbed dynamic shifts in subnetworks related to cell cycle, stress response, and RNA processing in oligodendrocytes. Cross cell-type ligand-receptor networks revealed the roles of App, Hmgb1, Fn1, and Tnf in mTBI, with the latter two ligands having been previously identified as TBI network hubs. mTBI and/or T4 signature genes were enriched for human genome-wide association study (GWAS) candidate genes for cognitive, psychiatric and neurodegenerative disorders related to mTBI. Our systems-level single cell analysis elucidated the temporal and spatial dynamic reprogramming of cell-type specific genes, pathways, and networks, as well as cell-cell communications as the mechanisms through which T4 mitigates cognitive dysfunction induced by mTBI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Previous research has demonstrated that concussions increase the risk of subsequent lower extremity musculoskeletal injury in athletes. However, the risk of upper extremity injury in athletes' post-concussion is poorly understood., Methods: All concussed football players within a National Collegiate Athletic Association (NCAA) Division I conference athletic database were identified between 2017 and 2021. After exclusions, each athlete experiencing their first concussion was then retrospectively reviewed for upper extremity injuries in the year prior to their concussion and in the year beginning at 90 days after their concussion. All upper extremity injuries were identified and the odds ratio, 95% confidence interval, and statistical significance between groups were calculated in Microsoft Excel., Results: 160 de-identified football players from a single conference who were first diagnosed with concussions in the seasons from 2017 through 2021 met inclusion criteria. In these athletes the odds of upper extremity injury in year following first diagnosed concussion were 2.36 times higher than in the year prior (95% CI 1.13-4.95, p  = 0.02). Shoulder was the most common site of injury with 57.7% of injuries compared to 19.2% in the hand, 15.4% in the elbow, 7.7% in the forearm, and 0% in the wrist., Conclusion: This study demonstrates that collegiate football players are at a 2.36 times greater risk of upper extremity injury in the year following their first diagnosed concussion compared to the year preceding it. The most common site of upper extremity injury after concussion was the shoulder., Level of Evidence: III.

Objective: To assess changes in health-related quality of life (HRQOL) across a 12-month period following pediatric concussion and to explore whether psychological factors (ie, preinjury mental health history, current symptoms of anxiety and depression, sleep disturbance, or grit) were associated with HRQOL., Study Design: Prospective cohort study design using data collected from patients presenting to a specialty care concussion program, with each patient followed for 12 months after initial presentation. Comparison data were collected from nonconcussed controls recruited from the community. A total of 49 concussed patients (median = 15.4 years of age) completed the Pediatric Quality of Life Inventory, Patient-Reported Outcome Measure Information Systems Anxiety and Depressive Symptoms short forms, Pediatric Sleep Disturbance forms, and a Short Grit Scale. Mixed effects models explored change in HRQOL across time., Results: Total HRQOL at initial clinic presentation was significantly lower for concussed adolescents (Pediatric Quality of Life Inventory total score mean = 72 [SD = 16]) compared with nonconcussed controls (mean = 88 [SD = 11], P < .001). HRQOL improved in the patients with concussion over a 6-month period after initial assessment with no significant changes thereafter. Preinjury history of anxiety (coefficient = -11.388, CI = -18.49 to -4.28, P < .001), current depressive symptoms (coefficient = -0.317, CI = -0.62 to -0.01, P < .01), and sleep disturbance (coefficient = -0.336, CI = -0.71 to 0.04, P < .05) all predicted lower HRQOL., Conclusions: HRQOL is significantly lower in the acute phase of pediatric concussion and steadily improves over the following 6 months. Psychological factors are linked to lower HRQOL and may serve as important indicators of risk for poor outcome., Competing Interests: Declaration of Competing Interest This work was funded by the Pennsylvania Department of Health, NIHR01NS097549, and the Frontier Program at the Children's Hospital of Philadelphia. The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Post-traumatic headache (PTH) is a common comorbid symptom affecting at least one-third of patients with mild traumatic brain injury (mTBI). While neuroinflammation is known to contribute to the development of PTH, the cellular mechanisms in the trigeminal system crucial for understanding the pathogenesis of PTH remain unclear., Methods: A non-invasive repetitive mTBI (4 times with a 24-h interval) was induced in male mice and effect of mTBI was tested on either bregma or pre-bregma position on the head. Periorbital allodynia and spontaneous pain behavior were assessed using von Frey test and grimace score, respectively. Quantitative PCR was used to assess extent of mTBI pathology. RNA sequencing was performed to obtain transcriptomic profile of the trigeminal ganglion (TG), trigeminal nucleus caudalis (Sp5C) and periaqueductal gray (PAG) at 7 days post-TBI. Subsequently, quantitative PCR, in situ hybridization and immunohistochemistry were used to examine mRNA and protein expression of glia specific markers and pain associated molecules., Results: The repetitive impacts at the bregma, but not pre-bregma site led to periorbital hypersensitivity, which was correlated with enhanced inflammatory gene expression in multiple brain regions. RNA sequencing revealed mTBI induced distinct transcriptomic profiles in the peripheral TG and central Sp5C and PAG. Using gene set enrichment analysis, positive enrichment of non-neuronal cells in the TG and neuroinflammation in the Sp5C were identified to be essential in the pathogenesis of PTH. In situ assays also revealed that gliosis of satellite glial cells in the TG and astrocytes in the Sp5C were prominent days after injury. Furthermore, immunohistochemical study revealed a close interaction between activated microglia and reactive astrocytes correlating with increased calretinin interneurons in the Sp5C., Conclusions: Transcriptomics analysis indicated that non-neuronal cells in peripheral TG and successive in situ assays revealed that glia in the central Sp5C are crucial in modulating headache-like symptoms. Thus, selective targeting of glia cells can be a therapeutic strategy for PTH attributed to repetitive mTBI., Competing Interests: Declarations. Ethics approval and consent to participate: All animal procedures were conducted in accordance with the Office for Laboratory Animal Welfare (OLAW), National Institutes of Health (NIH) and American Veterinary Medical Association (AVMA) Guidelines for the Euthanasia of Animals guidelines and approved by the Uniformed Services University of the Health Sciences (USUHS) Institutional Animal Care and Use Committee (IACUC). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

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 relationships 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 5000 bootstrap samples and a 95% confidence interval., Results: There was a significant interaction between the mean memory composite and depressive symptoms when predicting cognitive symptom reporting, p = 0.047. Simple effects tests revealed that for athletes who had a lower memory composite score, an increase in depressive symptoms led to an increase in self-reported cognitive dysfunction, p < 0.001, ηp2 = 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 reporting high depressive symptoms and cognitive dysfunction may need more comprehensive evaluations to inform return-to-play decisions, and depression could be a treatment target for athletes who report high levels of cognitive dysfunction after concussion., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To describe CONCUSS, a randomized clinical trial (RCT) designed to compare the following: the effectiveness of immediate office-based vergence/accommodative therapy with movement (OBVAM) to delayed OBVAM as treatments for concussion-related convergence insufficiency (CONC-CI) to understand the impact of time (watchful waiting), the effect of OBVAM dosage (12 versus 16 therapy sessions), and to investigate the underlying neuro-mechanisms of OBVAM on CONC-CI participants., Methods: CONCUSS is an RCT indexed on https://clinicaltrials.gov/study/NCT05262361 enrolling 100 participants aged 11-25 years with medically diagnosed concussion, persistent post-concussive symptoms 4-24 weeks post-injury, and symptomatic convergence insufficiency. Participants will receive standard concussion care and will be randomized to either immediate OBVAM or delayed (by six weeks) OBVAM. At the Outcome 1 examination (week 7), clinical assessments of success as determined by changes in the near point of convergence (NPC), positive fusional vergence (PFV), and symptoms will be compared between the two treatment groups. After the Outcome 1 visit, those in the delayed group receive 16 visits of OBVAM, while those in the immediate OBVAM group receive four more therapy visits. Outcome 2 assessment will be used to compare both groups after participants receive 16 sessions of OBVAM. The primary measure is the between-group differences of the composite change in the NPC and PFV at the Outcome 1 visit. Secondary outcome measures include individual clinical measures, objective eye-tracking parameters, and functional brain imaging., Conclusions: Major features of the study design include formal definitions of conditions and outcomes, standardized diagnostic and treatment protocols, a delayed treatment arm, masked outcome examinations, and the incorporation of objective eye movement recording and brain imaging as outcome measures. CONCUSS will establish best practices in the clinical care of CONC-CI. The objective eye movement and brain imaging, correlated with the clinical signs and symptoms, will determine the neuro-mechanisms of OBVAM on CONC-CI., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Alvarez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Memory and affective processing were compared in young adults with a remote mild traumatic brain injury (mTBI), to healthy younger and older adults. We evaluated memory performance when encoding was done under multi-tasking (divided attention) conditions, likely to exacerbate cognitive and psychological symptoms in mTBI., Methods: Participants studied pairs of unrelated words under either full or divided attention conditions. Memory for single words (item memory) and for pairs of words (associative memory) was then assessed in sequential independent recognition tests, under full attention., Results: Associative memory was poorer than item memory, and worse when encoding was done under divided than full attention. The decline in recognition accuracy from full to divided attention conditions on the associative memory test was significantly greater in mTBI compared to young adults and was similar in magnitude to that observed in older adults under full attention. Self-reported mental and total fatigue increased significantly as performance on the memory tests, following the divided attention condition, decreased, but only in the mTBI group., Conclusions: Results show lingering memory deficits, and suggest that cognitive tasks may be experienced as psychologically more demanding in those with a mTBI, even months or years after injury.

Primary Objective: This is Part II of a four-part opinion review on traditional neuropsychological assessment methods and findings associated with mild traumatic brain injury (mTBI). This Part II review focuses on historical, psychometric and statistical issues involving traditional neuropsychological methods that have been used in neuropsychological outcome studies of mTBI, but demonstrates the critical limitations of traditional methods., Research Design: This is an opinion review., Methods and Procedures: Traditional neuropsychological tests are dated and lack specificity in evaluating such a heterogenous and complex injury as occurs with mTBI., Main Outcome and Results: In this review, we demonstrate traditional neuropsychological methods were never developed as standalone measures for detecting subtle changes in neurocognitive or neurobehavioral functioning and likewise, never designed to address the multifaceted issues related to underlying mTBI neuropathology symptom burden from having sustained a concussive brain injury., Conclusions: For neuropsychological assessment to continue to contribute to clinical practice and outcome literature involving mTBI, major innovative changes are needed that will likely require technological advances of novel assessment techniques more specifically directed to evaluating the mTBI patient. These will be discussed in Part IV.

Background: The purpose of the study was to identify whether the presence of a pre-injury psychiatric history, subacute post-concussive symptoms (PCS) and personality traits were predictive of less favorable social reintegration for 3 months following a mild traumatic brain injury (mTBI)., Method: A total of 76 patients with mTBI were included, and the presence of a pre-injury psychiatric history was identified from the medical chart. One-month post-accident, these patients completed the Millon Multiaxial Clinical Inventory, 3rd Edition assessing personality traits and the Rivermead Post-Concussion Symptoms Questionnaire to measure subacute PCS. Social reintegration was measured using the Mayo-Portland Adaptability Inventory, 4th Edition at 3-month post-accident., Results: The presence of pre-injury psychiatric history, high levels of subacute PCS and Cluster B personality traits such as histrionic and borderline features were significant predictors of social reintegration quality at 3-month post injury., Conclusion: This study provides new insights on cluster B personality traits and its influence on recovery and social reintegration at 3-month post mTBI.

Despite increasing recognition of the significance of mild traumatic brain injury (mTBI), the long-term cognitive consequences of the injury remain unclear. More sensitive measures that can detect subtle cognitive changes and consideration of individual variability are needed to properly characterise cognitive outcomes following mTBI. Here, we used complex behavioural tasks, individual differences approaches, and electrophysiology to investigate the long-term cognitive effects of a history of mTBI. In Experiment 1, participants with self-reported mTBI history (n=82) showed poorer verbal working memory performance on the operation span task compared to control participants (n=88), but there were no group differences in visual working memory, multitasking, cognitive flexibility, attentional control, visuospatial ability, or information processing speed. Individual differences analyses revealed that time since injury and presence of memory loss predicted visual working memory capacity and visuospatial ability, respectively, in those with mTBI history. In Experiment 2, participants with mTBI history (n=20) again demonstrated poorer verbal working memory on the operation span task compared to control participants (n=38), but no group differences were revealed on a visuospatial complex span task or simpler visual working memory measures. We also explored the electrophysiological indices of visual working memory using EEG during a change detection task. No differences were observed in early sensory event-related potentials (P1, N1) or the later negative slow wave associated with visual working memory capacity. Together, these findings suggest that mTBI history may be associated with a lasting, isolated disruption in the subsystem underlying verbal working memory storage. The results emphasise the importance of sensitive cognitive measures and accounting for individual variability in injury characteristics when assessing mTBI outcomes., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: The neurobehavioral significance of white matter hyperintensities (WMHs) seen on magnetic resonance imaging after traumatic brain injury (TBI) remains unclear, especially in Veterans and Service Members with a history of mild TBI (mTBI). In this study, we investigate the relation between WMH, mTBI, age, and cognitive performance in a large multisite cohort from the Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium., Materials and Methods: The neuroimaging and neurobehavioral assessments for 1,011 combat-exposed, post-9/11 Veterans and Service Members (age range 22-69 years), including those with a history of at least 1 mTBI (n = 813; median postinjury interval of 8 years) or negative mTBI history (n = 198), were examined., Results: White matter hyperintensities were present in both mTBI and comparison groups at similar rates (39% and 37%, respectively). There was an age-by-diagnostic group interaction, such that older Veterans and Service Members with a history of mTBI demonstrated a significant increase in the number of WMHs present compared to those without a history of mTBI. Additional associations between an increase in the number of WMHs and service-connected disability, insulin-like growth factor-1 levels, and worse performance on tests of episodic memory and executive functioning-processing speed were found., Conclusions: Subtle but important clinical relationships are identified when larger samples of mTBI participants are used to examine the relationship between history of head injury and radiological findings. Future studies should use follow-up magnetic resonance imaging and longitudinal neurobehavioral assessments to evaluate the long-term implications of WMHs following mTBI., (© Oxford University Press 2024.)

Importance: Blast-related mild traumatic brain injuries (TBIs), the "signature injury" of post-9/11 conflicts, are associated with clinically relevant, long-term cognitive, psychological, and behavioral dysfunction and disability; however, the underlying neural mechanisms remain unclear., Objective: To investigate associations between a history of remote blast-related mild TBI and regional brain volume in a sample of US veterans and active duty service members., Design, Setting, and Participants: Prospective cohort study of US veterans and active duty service members from the Long-Term Impact of Military-Relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium (LIMBIC-CENC), which enrolled more than 1500 participants at 5 sites used in this analysis between 2014 and 2023. Participants were recruited from Veterans Affairs medical centers across the US; 774 veterans and active duty service members of the US military met eligibility criteria for this secondary analysis. Assessment dates were from January 6, 2015, to March 31, 2023; processing and analysis dates were from August 1, 2023, to January 15, 2024., Exposure: All participants had combat exposure, and 82% had 1 or more lifetime mild TBIs with variable injury mechanisms., Main Outcomes and Measures: Regional brain volume was calculated using tensor-based morphometry on 3-dimensional, T1-weighted magnetic resonance imaging scans; history of TBI, including history of blast-related mild TBI, was assessed by structured clinical interview. Cognitive performance and psychiatric symptoms were assessed with a battery of validated instruments. We hypothesized that regional volume would be smaller in the blast-related mild TBI group and that this would be associated with cognitive performance., Results: A total of 774 veterans (670 [87%] male; mean [SD] age, 40.1 [9.8] years; 260 [34%] with blast-related TBI) were included in the sample. Individuals with a history of blast-related mild TBI had smaller brain volumes than individuals without a history of blast-related mild TBI (which includes uninjured individuals and those with non-blast-related mild TBI) in several clusters, with the largest centered bilaterally in the superior corona radiata and subcortical gray and white matter (cluster peak Cohen d range, -0.23 to -0.38; mean [SD] Cohen d, 0.28 [0.03]). Additionally, causal mediation analysis revealed that these volume differences significantly mediated the association between blast-related mild TBI and performance on measures of working memory and processing speed., Conclusions and Relevance: In this cohort study of 774 veterans and active duty service members, robust volume differences associated with blast-related TBI were identified. Furthermore, these volume differences significantly mediated the association between blast-related mild TBI and cognitive function, indicating that this pattern of brain differences may have implications for daily functioning.

Background: Concussion and communication researchers have yet to study how post-concussion communication changes affect youths' daily lives. The lack of attention paid to how young people respond to communication changes during concussion recovery constitutes a significant gap in current concussion management research and practices., Aims: To explore how youth respond to the effects of post-concussion communication changes in their daily life, including (1) daily routines, (2) relationships with family members, (3) relationships with peers and (4) participation in school/work and community activities., Methods & Procedures: Five youths (16-25 years) and three family members participated in this arts-based reflexive collective case study. Ecocultural theory provided the theoretical framework for study design, data collection and analysis. Cases consist of (1) pre-interview demographic information, (2) three 60-90-min virtual interviews, (3) optional family member interviews, (4) multi-media arts-based participant-generated materials representing participants' experiences of communication change and concussion, and (5) researcher observations, discussions and reflexive journal entries. Reflexive thematic analysis was used to analyse the data., Outcomes & Results: Analysis yielded four themes that illustrate the ways youth navigated and adapted to post-concussion communication changes: (1) navigating changes in communication tasks, daily roles, and identity; (2) re-negotiating relationships and emotional reactions; (3) seeking control and learning to let go during recovery; and (4) helping youth adapt to post-concussion communication changes., Conclusions & Implications: The study findings deepen our understanding of the impact of post-concussion communication changes on youths' daily lives and underscore considerations critical to the development of communication-focused concussion education programs and interventions tailored specifically for youth., What This Paper Adds: What is already known on the subject Youth is a critical period of social and emotional development. Communication is integral to identity, relationships, participation in daily activities and well-being. Concussions can affect speech clarity, fluency, understanding and use of language, and social interactions. Re-engaging in routine activities and pre-injury roles can be challenging for youth experiencing communication changes as part of complex concussion recoveries. What this paper adds to the existing knowledge Findings from this research illuminate how youth navigate and adapt to communication changes post-concussion and support the development of youth-focused communication education programs, assessments and interventions. Youth participants actively managed their recoveries by developing innovative strategies to support their communication during daily activities, learning about communication, practicing communication tasks sequentially, and facing fears. Youth also reframed and challenged narrow views of 'normal communication'. What are the potential or actual clinical implications of this work? Findings highlight the need for more youth- and communication-focused education materials and programs within youth concussion management protocols. Information about the specific ecological and sociocultural factors youth encounter during concussion recovery is needed to develop targeted communication-focused education and intervention programs for youth and their families to mitigate risks of isolation, loneliness, and mental health concerns and increase youths' participation in family, community and cultural life. By learning from youth about how communication changes affected their participation in daily activities, identity and relationships, clinicians can provide information and interventions to reduce adverse listener reactions and help young people feel supported and understood., (© 2024 The Author(s). International Journal of Language & Communication Disorders published by John Wiley & Sons Ltd on behalf of Royal College of Speech and Language Therapists.)

Background: To investigate the long-term outcome of pediatric mild traumatic brain injury (mTBI) in terms of neurocognitive, behavioral, and school functioning and to identify clinical risk factors for adverse outcomes., Methods: This study describes the follow-up of a prospective multicenter sample of 89 children with mTBI 3.6 years postinjury and 89 neurologically healthy children matched for sex, age, and socioeconomic status. Neurodevelopmental outcomes were assessed using an intelligence test, behavioral questionnaires, computerized neurocognitive tests, and longitudinal (pre- and postinjury) standardized school performance data., Results: Children with mTBI exhibited intelligence in the average range but had more behavioral problems related to inattentiveness (P = 0.004, d = 0.47) and hyperactive impulsivity (P = 0.01, d = 0.40) and showed poorer neurocognitive performance in information processing stability (P = 0.003, d = -0.55) and Visual Working Memory (P = 0.04, d = -0.39) compared with matched peers. Longitudinal school performance data revealed poorer performance in Technical Reading up to two years postinjury (P = 0.005, d = -0.42) when compared with normative data. Clinical risk factors did not reveal predictive value for adverse outcomes in children with mTBI., Conclusions: This study indicates that children with mTBI are at risk of long-term deficits in neurocognitive and behavioral functioning, with longitudinal evidence suggesting shortfalls in school performance up to two years postinjury. Clinical risk factors do not provide a solid basis for long-term neurodevelopmental prognosis. Findings emphasize the importance of, and challenges for, early identification of children at risk for adverse neurodevelopmental outcome after mTBI., Competing Interests: Declaration of competing interest Conflicts of interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Concussion often results in psychological symptoms, including anxiety. Post-concussion anxiety has been well documented, although much of this research has focused on collegiate athletes. The purpose of this study was to compare (1) anxiety symptoms in concussed and healthy controls over time and (2) to explore sex differences in post-concussion anxiety within the context of pubertal development. Participants (N = 126, mean age = 15.1 years old), including concussed ( n  = 86) and healthy adolescents ( n  = 40), completed the Pubertal Development Scale (PDS) and the Screen for Child Anxiety and Related Disorders (SCARED-C). The concussed groups completed SCARED-C at three visits ( < 10 days, 4 weeks, 3 months). Results of an analysis of covariance (ANCOVA) and multi-variate analysis of covariance (MANCOVA) found concussed adolescents reported higher SCARED-C total, generalized, and panic anxiety scores than healthy controls, after controlling for sex, age, and PDS score (PDSS). A three-way mixed ANCOVA examined the effects of sex, PDSS, time, and their interaction on SCARED-C total score in concussed adolescents while controlling for age. There was a significant three-way interaction between sex, age, and PDSS on SCARED-C total score while controlling for age. Overall, we observed increased anxiety in concussed adolescents, compared with controls, as well as greater post-concussion anxiety reported by females compared with males, including within PDSS groups. Concussion providers should be prepared to receive training to administer well-validated measures of psychopathology and should consider that female adolescents, compared with males, regardless of pubertal development, may be at greater risk for post-concussion anxiety.

The objective of the current study was to investigate whether response time measures on the Word Memory Test (WMT) increase predictive validity on determining noncredible neurocognitive dysfunction in a large sample of mild traumatic brain injury (MTBI) litigants. Participants included 203 adults who underwent a comprehensive neuropsychological examination. Criterion groups were formed based upon their performance on stand-alone measures of cognitive performance validity (PVT). Participants failing PVTs exhibited significantly slower response times and lower accuracy on the WMT compared to participants who passed PVTs. Response time measures did not add significant incremental validity beyond that afforded by WMT accuracy measures alone. The best predictor of PVT status was the WMT Consistency Score (CNS) which was associated with an extremely large effect size ( d  = 16.44), followed by Immediate Recognition (IR: d  = 10.68) and Delayed Recognition (DR: d  = 10.10).

Assessing the credibility of symptoms is critical to neuropsychological assessment in both clinical and forensic settings. To this end, the Inventory of Problems-29 (IOP-29) and its recently added memory module (Inventory of Problems-Memory; IOP-M) appear to be particularly useful, as they provide a rapid and cost-effective measure of both symptom and performance validity. While numerous studies have already supported the effectiveness of the IOP-29, research on its newly developed module, the IOP-M, is much sparser. To address this gap, we conducted a simulation study with a community sample ( N  = 307) from the United Kingdom. Participants were asked to either (a) respond honestly or (b) pretend to suffer from mTBI or (c) pretend to suffer from depression. Within each feigning group, half of the participants received a description of the symptoms of the disorder to be feigned, and the other half received both a description of the symptoms of the disorder to be feigned and a warning not to over-exaggerate their responses or their presentation would not be credible. Overall, the results confirmed the effectiveness of the two IOP components, both individually and in combination.

Background and Objective: In the US military, traumatic brain injury (TBI) is of distinct importance, at home and in the deployed setting, and is considered a "signature injury of the wars in Afghanistan and Iraq." Since 2000, an estimated 468 424 service members (SMs) have been diagnosed with at least one TBI. We examined the clinical trajectories of a group of 18 comorbidities before and after a military-sustained mild TBI (mTBI)., Methods: Without making assumptions on causality, a group of 18 conditions often co-occurring with mTBI were identified through literature review and TBI subject matter workgroup consensus. Using data from Military Health System Data Repository, we identified SMs whose first lifetime military mTBI occurred between October 1, 2016, and October 30, 2019. Correlation analyses were used to determine the linear relationship between comorbidities prior to and after mTBI diagnosis. Changes in the period prevalence of comorbidities was calculated., Results: We identified 42 018 SMs with a first lifetime military mTBI, of which 77.6% had at least one comorbidity. Identified SMs were mostly young (46.1% ages 18-24 years), male (81.4%), and White (64.1%). Up to 180 days prior to an mTBI, the most frequently identified conditions were sleep-related conditions (21.7%), headaches (19.4%), posttraumatic stress disorders (PTSDs) (17.8%), anxiety disorders (11.3%), and cervicogenic disorders (eg, cervicalgia) (10.9%). In the period following mTBI diagnosis, the prevalence of diagnosed conditions increased, especially for visual disturbances (327.2%), cognitive conditions (313.9%), vestibular conditions (192.6%), those related to headache (152.2%), and hearing (72.9%). Sleep-related conditions showed moderate positive correlation with a group of co-occurring conditions, led by cognitive conditions ( ϕc = 0.50), anxiety disorders ( ϕc = 0.42), PTSDs ( ϕc =0.43), and headaches and related conditions ( ϕc = 0.38)., Conclusion: Results indicate that caring for SMs with mild TBI requires a holistic approach, one that considers the complex nature of SM conditions, prior to sustaining their mTBI, as well as after injury. We found a complex correlation of conditions that suggest SMs with mTBI are undergoing a multifaceted experience, one that may require the development of a targeted multidimensional clinical practice recommendation and practice., Competing Interests: The authors declare no conflicts of interests.

Objective: The evaluation of self-reported symptoms is a standard component of concussion assessment and management. Clinicians typically evaluate a total symptom severity score rather than scores corresponding to specific symptom domains (i.e., cognitive, sleep-arousal, physical, and affective symptoms). This study examined (i) whether elevations in specific symptom domains would be missed when interpreting only the total symptom severity score and (ii) if a single symptom domain elevation was more common than having elevated symptoms across multiple domains., Method: Adolescent student-athletes (N = 1,008) with concussion history (i.e., ≥6 months since last concussion) completed the Post-Concussion Symptom Scale (PCSS). The PCSS total score and cognitive, sleep-arousal, physical, and affective domain scores were calculated. To determine if symptoms were elevated, scores were compared to normative data matched on gender and pre-existing conditions, with scores considered elevated if they were ≥84th percentile. The frequency of total and domain score elevations were calculated and stratified by gender and number of prior concussions (i.e., 1 or ≥2 prior concussions)., Results: Overall, 26% of student-athletes had an elevated symptom domain score without being elevated on the total score. The most common symptom presentation was to have a single elevated symptom domain (21%), followed by two (11%), three (8%), or four elevated domains (6%)., Conclusions: Interpreting PCSS symptom domains may be beneficial in detecting student-athletes with elevated symptoms following a remote concussion. Roughly a quarter of student-athletes have domain-specific symptom elevations that would be missed by interpreting the total score alone., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Early Exercise Intolerance (EEI) is associated with delayed recovery and longer time to Return To Play (RTP), but this has not been established.Participants; ( n  = 52, male n  = 30) UK university-aged rugby-union student-athletes., Methods: Student-athletes completed baseline screening (July-October 2021 and 2022). The test battery was repeated within 48 h, 4, 8 and 14 days after a Sports-Related Concussion (SRC) with the Buffalo Concussion Bike or Treadmill Test to set sub-symptom heart rate threshold. Student-athletes then completed a controlled early exercise protocol in-between reassessment (days 3, 5-7 and 9-13). Those with EEI were compared to those with early-exercise tolerance., Outcome Measures: Post-Concussion Symptom Scale, Immediate Post-Concussion and Cognitive Test, Vestibular-Ocular Motor Screening Tool and the Revised Perceived Academic Impact Tool., Results: EEI was seen throughout the initial 14-days post-SRC (23.8%, 22.4%, 25.5%. 25.0%). EEI was associated with a slower reaction time within 48 h (-0.01 (-0.030-0.043) Vs 0.06 (0.033-0.24), p  = 0.004) and greater VOMS scores within 48 h; (0.00 (0.00-4.00) Vs 5.50 (2.75-9.00), p  = 0.016) and 4 days (0.00 (0.00-2.00) Vs 5.00 (0.00-6.00), p  = 0.044). RTP was 12.5 days longer in those with EEI at 14-days post-SRC., Conclusion: EEI is prevalent following an SRC in university-aged student-athletes and was associated with delayed recovery and RTP.

Objective: To provide healthcare professionals guidance on youth at risk for prolonged recovery and post-traumatic headache (PTH), and on pharmacologic and non-pharmacologic management of PTH due to concussion and mild traumatic brain injury., Background: Headache is the most common persistent post-concussive symptom affecting 8% of youth for >3 months after concussion. Over the past decade, many studies have explored the treatment of PTH in youth, but there are no established guidelines., Methods: This white paper is based on a synthesis of an updated systematic review of the literature on treatment of PTH and a narrative review of the literature on risk factors for prolonged recovery and health disparities. Results were interpreted by a group of expert providers in PTH in children and adolescents through collaboration of the PTH and pediatric special interest groups of the American Headache Society., Results: Factors that consistently were associated with prolonged recovery from concussion and persistent PTH included female sex, a high number of acute symptoms, and adolescent age. Social determinants of health also likely play an important role in PTH and deserve consideration in the clinical and research settings. A total of 33 studies met the criteria for inclusion in the systematic review of PTH treatment in youth, although most were retrospective and of fair-to-poor quality. Treatment strategies included acute and preventive pharmacologic management, procedures, neuro-modulatory devices, physical therapy, physical activity, and behavioral health support. A collaborative care approach that includes a thoughtful combination of these management strategies is likely most effective., Conclusions: This white paper provides a roadmap for tailoring the treatment of PTH based on factors influencing prolonged headache, the timing of therapies, and therapies with the most evidence for treating PTH in youth. We also highlight research needed for developing more definitive guidelines on PTH management in youth., (© 2024 The Author(s). Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.)

Objective: To examine gender differences in Australian football (AF)-related concussion presentations to EDs in regional Australia., Methods: A prospective observational study of patients presenting to 1 of the 10 EDs in Western Victoria, Australia, with an AF-related concussion was conducted. Patients were part of a larger study investigating AF injuries over a complete AF season, including pre-season training and practice matches. Information regarding concussion injuries was extracted from patient medical records, including clinical features, concurrent injuries, mechanism and context of injury. Female and male data were compared with chi-squared and Fisher's exact tests. P < 0.05 was considered significant., Results: From the original cohort of 1635 patients with AF-related injuries (242 female and 1393 male), 231 (14.1%) patients were diagnosed with concussion. Thirty-eight (15.7%) females had concussions versus 193 (13.9%) males (P > 0.05). Females over the age of 16 were more likely to be concussed than males in the same age range (females n = 26, 68.4% vs males n = 94, 48.7%; P = 0.026). Neurosurgically significant head injury was rare (one case). Similar rates of concurrent injury were found between females 15 (39.5%) and males 64 (33.2%), with neck injury the single most common in 24 (10.3%) concussions. Sixty-nine patients (29%) were admitted for observation or to await the results of scans. The majority of concussions occurred in match play (87.9%). Females were more likely injured in contested ball situations (63.2% vs 37.3%; P < 0.05)., Conclusion: Concussion rates for community-level AF presentations to regional EDs were similar between genders. Serious head injury was rare, although hospital admission for observation was common. Concurrent injuries were common, with associated neck injury most often identified. Match play accounted for the majority of head injuries., (© 2024 Australasian College for Emergency Medicine.)

Background: Mild traumatic brain injuries (mTBIs) pose a significant risk, particularly in the elderly population on anticoagulation therapy. The safety of discharging these patients from the emergency department (ED) with a negative initial computed tomography (CT) scan has been debated due to the risk of delayed intracranial hemorrhage (d-ICH)., Objective: To compare outcomes, including d-ICH, between elderly patients on anticoagulation therapy presenting with mTBI who were admitted versus discharged from the ED after an initial negative head CT scan., Methods: We conducted a retrospective observational study at the Chaim Sheba Medical Center, assessing outcomes of 1598 elderly patients on anticoagulation therapy who presented with mTBI and an initial negative head CT scan. Patients were either admitted for 24-h observation (Group A, n = 829) or discharged immediately from the ED (Group B, n = 769). The primary outcome was incidence of d-ICH within 14 days., Results: Among the 1598 patients included in the study, 46 admitted patients and 1 discharged patient returned within 14 days for repeat CT, identifying one asymptomatic hemorrhage in the discharged patient. Mortality at 30 days was significantly higher in admitted patients compared to discharged patients (4.8% vs. 1.8%, p = 0.001), though cause of death was unrelated to head injury in both groups., Conclusion: In elderly patients on anticoagulation with mTBI and a negative initial CT, admission was associated with a higher risk of d-ICH compared to discharge. These findings have implications for clinical decision-making in this high-risk population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Investigate whether a four-factor model of post-concussion symptoms (i.e. cognitive, physical, affective, and sleep-arousal) aids in identifying student-athletes with persistent concerns not reflected by a total symptom score. Method: Collegiate student-athletes ( N  = 32,066) from the Concussion Assessment Research and Education consortium completed the Sport Concussion Assessment Tool, 3rd edition Symptom Evaluation at baseline and two post-injury follow-ups (i.e. beginning RTP and 6-month). Confirmatory factor analysis was used to compare a one- and four-factor model of post-concussion symptoms. Normative reference data were compared across stratifications (e.g. sex, prior concussions, and number of pre-existing conditions) using Mann-Whitney U tests, and elevation rates (i.e. ≥ 84th percentile) for subscales and the total score were recorded. Results: The four-factor model fit well before and after injury (CFIs > .95). Greater symptom severity on the subscale and total scores was associated with female sex ( ps <.001, r range: .07 to .14) and more pre-existing conditions ( ps <.001, η 2 range: .01 to .04), while having more prior concussions was only related to total symptom scores ( ps <.001, η 2 <.01). After a concussion, a sizeable portion of student-athletes (i.e., RTP = 11.8%; 6-month = 8.3%) had subscale elevations despite no total score elevation. Physical subscale elevations at RTP were the most common (i.e., 11.9%), driven by head and neck pain. Conclusion: After a sport-related concussion, a four-factor symptom model can be used to assess persistent symptoms in collegiate student-athletes. Identifying athletes with domain-specific elevations may help clinicians identify areas for further assessment and, in some cases, personalized rehabilitation plans.

Backgroung: Mild traumatic brain injury (mTBI) encompasses a spectrum of disability including early cognitive impairment (ECI). The Brain Injury Guidelines suggest that patients with mTBI can be safely discharged from the emergency department. Although half of patients with mTBI with intracranial hemorrhage (ICH) have evidence of ECI, it is unclear what percentage of these patients' ECI persists after discharge. We hypothesize a significant proportion of trauma patients with mTBI and ECI at presentation have persistent ECI at 30-day follow-up., Study Design: A single-center prospective cohort study including adult trauma patients with ICH or skull fracture and a Glasgow Coma Scale of 13 to 15 on arrival was performed. Participants were screened for ECI using the Rancho Los Amigos Scale (RLA), and ECI was defined as an RLA less than 8. We compared ECI and non-ECI groups for demographics, injury profile, CT imaging (eg Rotterdam CT score) and outcomes with bivariate analysis. Thirty-day follow-up telephone calls were performed to re-evaluate RLA for persistent ECI and concussion symptoms., Results: From 62 patients with ICH or skull fracture and mTBI, 21 (33.9%) had ECI. Patients with ECI had a higher incidence of subarachnoid hemorrhage (85.7% vs 46.3%, p = 0.003) and higher Rotterdam CT score (p = 0.004) compared with those without ECI. On 30-day follow-up, 6 of 21 (26.6%) patients had persistent ECI. In addition, 7 (33.3%) patients had continued concussion symptoms., Conclusions: More than one-third of mTBI patients with ICH had ECI. At 30-day postdischarge follow-up, more than one-fourth of these patients had persistent ECI and 33% had concussion symptoms. This highlights the importance of identifying ECI before discharge as a significant portion may have ongoing difficulties reintegrating into work and society., (Copyright © 2024 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Return to play (RTP) protocols are an important part of recovery management following a sport-related concussion (SRC) and can prevent athletes from returning to competition too early and thereby avoid prolonged recovery times. To assist sporting organizations in the development of RTP guidelines, the Concussion in Sports Group (CISG) provides scientific-based recommendations for the management of SRC in its consensus statement on concussion in sport., Objectives: This study investigates commonalities and differences among current RTP protocols of international sporting organizations and examines the implementation of the most recent CISG recommendations., Methods: Concussion guidelines and medical rules of 12 international sporting organizations from contact, collision and combat sports were accessed via the organizations websites and compared regarding the management of SRC and the RTP decision., Results: Only six of the included organizations developed and published their own concussion guidelines, which included an RTP protocol on their website. The number of steps until RTP was similar across the different protocols. Each protocol required at least one medical examination before clearing an athlete to RTP. A high variation among organizations was found for initial resting period after injury, the implementation of sport-specific training drills and the time needed to complete the protocol before returning to competition. At the date of this study (9 September 2023), none of the accessible RTP protocols were updated to include the latest version of the CISG consensus statement., Conclusion: To improve the safety of athletes after a head injury, sporting organizations should develop sport-specific guidelines according to the latest CISG consensus statement, and this should be updated regularly. Implementation is especially important in combat sports, where there is a high incidence of head injury. Thus, there is a requirement for the most up-to-date concussion management protocols in these sports.

Head trauma often impairs cognitive processes mediated within the prefrontal cortex (PFC), leading to impaired decision making and risk-taking behavior. Mild traumatic brain injury (mTBI) accounts for approximately 80 % of reported head injury cases. Most neurological symptoms of a single mTBI are transient; however, growing evidence suggests that repeated mTBI (rmTBI) results in more severe impairments that worsen with each subsequent injury. Although mTBI-induced disruption of risk/reward decision making has been characterized, the potential for rmTBI to exacerbate these effects and the neural mechanisms involved are unknown. Catecholamine neurotransmitters, dopamine (DA) and norepinephrine (NE), modulate PFC-mediated functions. Imbalances in catecholamine function have been associated with TBI and may underlie aberrant decision making. We used a closed head-controlled cortical impact (CH-CCI) model in rats to evaluate the effects of rmTBI on performance of a probabilistic discounting task of risk/reward decision making behavior and expression levels of catecholamine regulatory proteins within the PFC. RmTBI produced transient increases in risky choice preference in both male and female rats, with these effects persisting longer in females. Additionally, rmTBI increased expression of the catecholamine synthetic enzyme, tyrosine hydroxylase (TH), within the orbitofrontal (OFC) region of the PFC in females only. These results suggest females are more susceptible to rmTBI-induced disruption of risk/reward decision making behavior and dysregulation of catecholamine synthesis within the OFC. Together, using the CH-CCI model of rodent rmTBI to evaluate the effects of multiple insults on risk-taking behavior and PFC catecholamine regulation begins to differentiate how mTBI occurrences affect neuropathological outcomes across different sexes., Competing Interests: Declaration of Competing Interest No competing financial interests exist., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Following mild traumatic brain injury (mTBI), children show reduced processing speed (PS). Evidence suggests that slowed PS after TBI is associated with working memory deficits. Our aim was to investigate several forms of PS and to examine its impact on working and episodic memory performance in children after mTBI., Method: We included data of 64 children after mTBI and 57 healthy control children aged 8-16 years. PS (Color Naming, Coding, Symbol Search, Alertness) was compared between groups 1 week (T1) and 3-6 months (T2) after the injury; working and episodic memory outcome was compared between groups at T2., Results: Alertness at T1 and Color Naming at T1 and T2 were significantly reduced following mTBI compared to controls, although most group differences in PS disappeared when patients with previous impairments and mTBI were excluded. PS was predictive for episodic and working memory performance 3-6 months after injury, whereas group was a significant predictor of working memory., Conclusions: Compared to healthy controls, children after mTBI showed reduced performance in verbal PS, which was associated with working memory. In children who are symptomatic after mTBI, diagnostic screening of PS could be helpful in identifying patients that could profit from speed-improving strategies.

Objective: Persistent symptoms post-mild traumatic brain injury (mTBI) includes autonomic dysregulation (AD). The composite autonomic symptoms score, (COMPASS-31), was developed to quantify AD symptom severity in the last year, which limits clinical utility. The primary aim was to determine validity of a modified-COMPASS-31 measuring symptoms in the last month compared to the original, secondarily to compare both original and modified versions to the Neurobehavioral Symptom Inventory (NSI), and tertiarily to detect change post-treatment of the modified-COMPASS-31 compared to NSI and headache intensity (HI)., Participants: Thirty-three military personnel with persistent headache post-mTBI., Main Outcome Measures: Total and domain scores for COMPASS-31 (original vs. modified) NSI and HI at baseline. Change in modified-COMPASS-31. NSI, and HI., Results: Baseline COMPASS-31 versions were comparable and highly correlated ( r  = 0.72, p  < 0.001), they were moderately correlated at best to the NSI ( r  < 0.6), which may suggest differences in measurement metrics. The mean change in modified-COMPASS-31 scores (15.4/100, effect size 0.8) was mild to moderately correlated to the change in HI ( r  = 0.39) score, but not to NSI ( r  = 0.28)., Conclusion: The modified-COMPASS-31 appears to be valid, can measure change of AD symptom severity, and is recommended as an outcome measure.

Objective: Considering that diagnostic decisions about mTBI are often predicated on clinical symptom criteria, it is imperative to determine which initial presentation features of mTBI have prognostic significance for identifying those at high risk for long-term functional impairment., Setting: Zoom interview Participants: Male, former NCAA Division I, and professional-level National Football League (NFL) athletes ( n  = 177) between the ages of 27 and 85 ( M  = 54.1, SD = 14.7)., Design: Cross-sectional case-control. Main Measures: History of mild TBI, history of loss of consciousness (LOC), depression symptoms, insomnia, neurobehavioral symptoms., Results: Number of mTBI exposures did not predict neurobehavioral symptoms (B = 0.21, SE = 0.18, p  = 0.23), but number of mTBI + LOC events did (B = 2.27, SE = 0.64, p  = <.001). Further analysis revealed that the number of mTBI + LOC events predicted neurobehavioral symptoms indirectly through both depression (B = 0.85, 95% CI = [0.27, 1.52) and insomnia (B = 0.81, 95% CI = [0.3, 1.4]). Further, the direct effect of mTBI + LOC events on neurobehavioral symptoms became non-significant when depression and insomnia were added to the model (B = 0.78, SE = 0.45, p  = 0.08)., Conclusions: Findings support LOC at time of injury as an important predictor of long-term outcomes. Additionally, results suggest depression and insomnia as potential mediators in the association between mTBI + LOC and neurobehavioral symptoms. These findings provide justification for early depression and insomnia symptom monitoring following mTBI + LOC.

Background: Mild traumatic brain injury (mTBI), i.e. a TBI with an admission Glasgow Coma Scale (GCS) of 13-15, is a common cause of emergency department visits. Only a small fraction of these patients will develop a traumatic intracranial hemorrhage (tICH) with an even smaller subgroup suffering from severe outcomes. Limitations in existing management guidelines lead to overuse of computed tomography (CT) for emergency department (ED) diagnosis of tICH which may result in patient harm and higher healthcare costs., Objective: To perform a systematic review and meta-analysis to characterize known and potential novel risk factors that impact the risk of tICH in patients with mTBI to provide a foundation for improving existing ED guidelines., Methods: The literature was searched using MEDLINE, EMBASE and Web of Science databases. Reference lists of major literature was cross-checked. The outcome variable was tICH on CT. Odds ratios (OR) were pooled for independent risk factors., Results: After completion of screening, 17 papers were selected for inclusion, with a pooled patient population of 26,040 where 2,054 cases of tICH were verified through CT (7.9%). Signs of a skull base fracture (OR 11.71, 95% CI 5.51-24.86), GCS < 15 (OR 4.69, 95% CI 2.76-7.98), loss of consciousness (OR 2.57, 95% CI 1.83-3.61), post-traumatic amnesia (OR 2.13, 95% CI 1.27-3.57), post-traumatic vomiting (OR 2.04, 95% CI 1.11-3.76), antiplatelet therapy (OR 1.54, 95% CI 1.10-2.15) and male sex (OR 1.28, 95% CI 1.11-1.49) were determined in the data synthesis to be statistically significant predictors of tICH., Conclusion: Our meta-analysis provides additional context to predictors associated with high and low risk for tICH in mTBI. In contrast to signs of a skull base fracture and reduction in GCS, some elements used in ED guidelines such as anticoagulant use, headache and intoxication were not predictive of tICH. Even though there were multiple sources of heterogeneity across studies, these findings suggest that there is potential for improvement over existing guidelines as well as a the need for better prospective trials with consideration for common data elements in this area. PROSPERO registration number CRD42023392495., (© 2024. The Author(s).)

Activation of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is a moderating factor between obesity and cognitive impairment in animals, but this has never been tested in humans following mild traumatic brain injury (mTBI). This is a retrospective cohort analysis of subjects enrolled at a single level 1 trauma center (n = 172). Participants completed Trail Making Test Part A and B (TMT-A and B) at six- and twelve-months, Blood samples were obtained within 24 h of mTBI and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, interleukin-18 (IL-18), and IL-1β were assayed. Obese participants (BMI = 30-34.9) were associated with higher IL-18 (p = 0.03) and IL-1β (p = 0.05) and severely obese participants (BMI > 35.0) were associated with higher IL-1β (p = 0.005) than healthy weight participants. IL-1β was associated with TMT-A at six- (p = 0.01) and twelve-months (p = 0.03) and TMT-B at twelve-months (p = 0.046). The interaction of severely obese BMI and IL-1β was associated with TMT-B at six- (p = 0.049) and twelve-months (p = 0.02). ASC (p = 0.03) and the interaction of ASC with severely obese BMI was associated with TMTB at six- (p = 0.02) and twelve-months (p = 0.02). Obesity may augment acute inflammasome response to mTBI and influence worse long-term cognitive outcomes up to one-year post-injury., Competing Interests: Declaration of competing interest The authors have no competing interests to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Objective: To develop an evidence and consensus-based clinical recommendation (CR) regarding primary care management of insufficient and disturbed sleep associated with concussion/mild traumatic brain injury (mTBI) in service members and veterans., Participants: A multidisciplinary expert working group (EWG) of 23 subject matter experts was selected by the Defense Health Agency (DHA) Traumatic Brain Injury Center of Excellence (TBICoE), based on relevant expertise and experience, from candidates nominated by DHA communities of interest., Evidence: The TBICoE core working group (CWG) conducted a literature search using PubMed and Google Scholar databases for articles relevant to sleep and mTBI from 2014 to 2018. Resulting studies were reviewed by the CWG, and questions addressing gaps in the literature were formulated., Consensus Process: Questions addressing gaps in the literature were distributed to the EWG, and consensus was achieved over the course of 5 online meetings. Based on the available evidence and EWG consensus, TBICoE developed a draft of the clinical recommendations and submitted it to the EWG for review and feedback. Feedback was adjudicated by TBICoE, and areas of nonconsensus were addressed via email utilizing a modified Delphi method., Conclusion: The evidence and EWG agree that addressing sleep early following mTBI is imperative to promoting recovery and preventing chronic mTBI symptoms, maladaptive sleep behaviors, and chronic sleep disorders., Prim Care Companion CNS Disord 2024;26(5):23nr03691 ., Author affiliations are listed at the end of this article., (© Copyright 2024 Physicians Postgraduate Press, Inc.)

Importance: Blood-based biomarkers may clarify underlying neuropathology and potentially assist in clinical management of adolescents with sport-related concussion (SRC)., Objective: To investigate the association between SRC and plasma biomarkers in adolescents., Design, Setting, and Participants: Prospective cohort study in Canadian sport and clinic settings (Surveillance in High Schools and Community Sport to Reduce Concussions and Their Consequences study; September 2019 to November 2022). Participants were a convenience sample of 849 adolescent (ages 10-18 years) sport participants with blood samples. Data were analyzed from February to September 2023., Exposures: Blood collection and clinical testing preseason (uninjured) and post-SRC follow-ups (ie, ≤72 hours, 1 week, and biweekly until medical clearance to return to play [RTP])., Main Outcomes and Measures: Plasma glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase-L1 (UCH-L1), neurofilament light (NfL), and total tau (t-tau) were assayed. Group-level comparisons of biomarker levels were conducted between uninjured and post-SRC intervals (postinjury day [PID] 0-3, 4-10, 11-28, and >28) considering age and sex as modifiers. Secondary analyses explored associations between biomarker concentrations and clinical outcomes (Sport Concussion Assessment Tool, Fifth Edition [SCAT5] symptom scores and time to RTP)., Results: This study included 1023 plasma specimens from 695 uninjured participants (467 male participants [67.2%]; median [IQR] age, 15.90 [15.13-16.84] years) and 154 participants with concussion (78 male participants [51.0%]; median [IQR] age, 16.12 [15.31-17.11] years). Acute (PID 0-3) differences relative to uninjured levels were found for GFAP (female participants: 17.8% increase; β = 0.164; 95% CI, 0.064 to 0.263; P = .001; male participants: 17.1% increase; β = 0.157; 95% CI, 0.086 to 0.229; P < .001), UCH-L1 (female participants: 43.4% increase; β = 0.361; 95% CI, 0.125 to 0.596; P = .003), NfL (male participants: 19.0% increase; β = 0.174; 95% CI, 0.087 to 0.261; P < .001), and t-tau (female participants: -22.9%; β = -0.260; 95% CI, -0.391 to -0.130; P < .001; male participants: -18.4%; β = -0.203; 95% CI, -0.300 to -0.106; P < .001). Differences were observed for all biomarkers at PID 4 to 10, 11 to 28, and greater than 28 compared with uninjured groups. GFAP, NfL, and t-tau were associated with SCAT5 symptom scores across several PID intervals. Higher GFAP after 28 days post-SRC was associated with earlier clearance to RTP (hazard ratio, 4.78; 95% CI, 1.59 to 14.31; P = .01). Male participants exhibited lower GFAP (-9.7%), but higher UCH-L1 (21.3%) compared with female participants. Age was associated with lower GFAP (-5.4% per year) and t-tau (-5.3% per year)., Conclusions and Relevance: In this cohort study of 849 adolescents, plasma biomarkers differed between uninjured participants and those with concussions, supporting their continued use to understand concussion neuropathology. Age and sex are critical considerations as these biomarkers progress toward clinical validation.

Background: Previous literature suggests that lingering concussion symptoms may be influenced by psychological factors. The relationship of posttraumatic stress symptoms (PTSS) during recovery with pre-existing/injury related factors and concussion symptomology is not fully understood. Identification of factors contributing to symptoms of posttraumatic stress may provide guidance to improve treatment following concussion., Method: This study included 287 participants (Male 40.42%, n  = 116; Female 59.58%, n  = 171) aged 13-75 years diagnosed with a recent concussion at one of the North Texas Concussion Registry (ConTex) specialty concussion clinic sites. Preinjury emotional history, injury related factors, and emotional state at time of initial evaluation were analyzed as predictors of post-traumatic stress symptoms (PCL-5) during recovery., Results: Sixty-one percent of participants endorsed at least one PTSS. Correlations were found between initial Sport Concussion Assessment Tool 5 Ⓡ (SCAT5) total emotional symptom severity and screening measures for anxiety (GAD-7; r  = .453, p  < .001) and depression (PHQ-8; r  = .550, p  < .001) symptom scores. Of the measures from the initial visit included in the multiple regression model predicting severity of PTSS at follow-up (R 2  = 0.554, β < .001), three measures predicted PTSS severity: initial SCAT5 total emotional symptom severity (β = 0.565, p  < .001), PHQ-8 score (β =.166, p  = .009), and GAD-7 score (β = 0.119, p  = .044)., Conclusions: Symptoms of anxiety and depression along with specific SCAT5 emotional symptoms present at the time of initial evaluation may serve to predict overall level of PTSS and increased risk for PTSS during recovery. PTSS may be another dimension of response to injury and concussion recovery, with a large percentage of individuals endorsing at least one PTSS. Clinicians can utilize brief assessments such as the SCAT5 at the time of initial clinical evaluation to identify those at risk for PTSS following concussion.

Mild traumatic brain injury (mTBI) and posttraumatic stress are prevalent in military service members and share objective and subjective cognitive symptoms, complicating recovery. We investigated the effects of remote mTBI characteristics and current posttraumatic stress symptoms on neuropsychological performance in 152 veterans with a history of remote mTBI and current cognitive concerns. Participants completed clinical neuropsychological evaluations within a Veterans Affairs Level-II TBI/Polytrauma outpatient clinic (i.e. tertiary trauma care center for US military veterans outside of a research or teaching hospital setting). Archival data analysis of mTBI injury characteristics, clinical diagnoses, scores on the Posttraumatic Stress Disorder Checklist-Military Version (PCL-M) and performance on tests of processing speed, attention and executive function was conducted. Hierarchical linear regression demonstrated that elevated PCL-M scores were associated with slower performance on trail making test (TMT) Parts A and B (p < .016). PCL-M symptoms moderated the effect of alteration of consciousness (AOC) on TMT performance, with endorsement of AOC associated with better performance, but only when PCL-M scores were high (p < .005). Follow-up mediation analyses demonstrated that PCL-M score fully mediated the relationship between AOC and TMT-A performance and partially mediated the relationship between AOC and TMT-B performance. Post-hoc analyses meant to separate the impact of processing speed on TMT-B were all non-significant. Remote mTBI characteristics, specifically AOC, were not associated with decrements in cognitive performance. Posttraumatic symptoms were associated with worse processing speed, suggesting that psychological distress and psychopathology are contributing factors in understanding and treating persistent cognitive distress following remote mTBI., (© 2024 The British Psychological Society.)

Objectives: People may experience a myriad of symptoms after mild traumatic brain injury (mTBI), but the relationship between symptoms and objective assessments is poorly characterized. This study sought to investigate the association between symptoms, resting heart rate (HR), and exercise tolerance in individuals following mTBI, with a secondary aim to examine the relationship between symptom-based clinical profiles and recovery., Methods: Prospective observational study of adults aged 18 to 65 years who had sustained mTBI within the previous 7 days. Symptoms were assessed using the Post-Concussion Symptom Scale, HR was measured at rest, and exercise tolerance was assessed using the Buffalo Concussion Bike Test. Symptom burden and symptom-based clinical profiles were examined with respect to exercise tolerance and resting HR., Results: Data from 32 participants were assessed (mean age 36.5 ± 12.6 years, 41% female, 5.7 ± 1.1 days since injury). Symptom burden (number of symptoms and symptom severity) was significantly associated with exercise intolerance ( P = .002 and P = .025, respectively). Physiological and vestibular-ocular clinical profile composite groups were associated with exercise tolerance ( P = .001 and P = .014, respectively), with individuals who were exercise intolerant having a higher mean number of symptoms in each profile than those who were exercise tolerant. Mood-related and autonomic clinical profiles were associated with a higher resting HR (>80 bpm) ( P = .048 and P = .028, respectively), suggesting altered autonomic response for participants with symptoms relating to this profile. After adjusting for age and mechanism of injury (sports- or non-sports-related), having a higher mood-related clinical profile was associated with persisting symptoms at 3 months postinjury (adjusted odds ratio = 2.08; 95% CI, 1.11-3.90; P = .013)., Conclusion: Symptom-based clinical profiles, in conjunction with objective measures such as resting HR and exercise tolerance, are important components of clinical care for those having sustained mTBI. These results provide preliminary support for the concept that specific symptoms are indicative of autonomic dysfunction following mTBI., Competing Interests: Competing interests: Prof Melinda Fitzgerald declares her role as CEO of Connectivity Traumatic Brain Injury Australia Ltd. Dr Gill Cowen declares her role as Chairperson of the Western Australian Concussion Network. All other authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Sport-related concussions (SRC) represent a significant concern for athletes. While popular contact sports such as football and soccer have been the focus of much SRC research, wrestling has received comparatively little attention. The current study aimed to: 1) describe the mechanisms of injury leading to SRC in wrestling; and 2) compare recovery outcomes based on mechanism of injury., Methods: A retrospective, cohort study of wrestlers aged 12-18 who sustained a concussion between 11/2017-04/2022 was performed. Contact mechanism was defined as what initiated contact with the athlete's head/body. Player mechanism was defined as the activity the injured athlete was performing when the concussion occurred. Recovery outcomes were compared using Mann-Whitney-U Tests and multivariable regression analysis., Results: Seventy-three (age=15.8±1.4 years; boys=73 [100.0%]) wrestlers were included. SRCs occurred more often in competition than in practice (66.2% vs. 33.8%, respectively). Head-to-ground/wall (56.2%) and takedown (58.9%) were the most common contact and player mechanisms, respectively. Bivariate analysis showed that head-to-head/body SRCs had longer time to symptom resolution compared to head-to-ground/wall SRCs (23.0 [14.8-46.5] vs. 14.0 [6.0-30.0] days; U=149.00, P=0.029), though the difference did not persist in multivariable analysis. For player mechanism, non-takedowns SRCs had longer time to symptom resolution than takedown SRCs (15.0 [6.0-24.0] vs. 28.5 [13.0-49.3]; U=166.5, P=0.019), but the difference also did not persist in multivariable analysis. Bivariate analysis revealed no significant difference in RTL between takedown and non-takedown SRCs (3.0 [2.0-6.0] vs. 4.0 [1.5-7.0]; U=484.50, P=0.708); however, in multivariable analysis, takedown SRCs were associated with longer RTL (β=0.23, 95% CI: 0.02, 9.27; P=0.049)., Conclusions: The current study found that SRCs occurred more commonly during competitions, and head-to-ground/wall and takedown were the most common contact and player mechanism, respectively. SRCs that occurred during takedowns were associated with longer RTL.

Objective: Although a majority of individuals recover from a concussion within weeks of the index injury, a substantial minority of patients report persistent postconcussion symptoms. Some of these symptoms may reflect a diagnosis of functional neurological disorder (FND). The authors evaluated the relationship between persistent postconcussion symptoms and FND symptoms., Methods: In this retrospective chart review, the authors characterized demographic and clinical information from 50 patients with a confirmed diagnosis of FND whose functional neurological symptoms started after a concussion., Results: Patients who developed FND after a concussion had high rates of baseline risk factors for both persistent postconcussion symptoms and FND. After the concussive event, functional neurological symptoms presented abruptly or developed insidiously over time. Functional neurological symptoms ranged widely and included gait symptoms, seizures, speech and language symptoms, weakness, sensory symptoms, tremors, and vision and oculomotor symptoms., Conclusions: Functional neurological symptoms can arise after a concussion. FND should be considered in the differential diagnosis of individuals presenting with neurological symptoms beginning after a concussion. By failing to recognize functional symptoms, clinicians may inadvertently reinforce negative health-related beliefs regarding a patient's injured brain., Competing Interests: Dr. Polich has received funding from the Foundation for Physical Medicine and Rehabilitation to study rhythmic auditory stimulation for functional gait disorders. Dr. Baslet has received royalties from Oxford University Press and payment for lectures on functional neurological disorders. Dr. O’Neal has received royalties from Oxford University Press, Springer, and UpToDate and has served as a consultant to Crico and Teladocs. Dr. Gupta reports no financial relationships with commercial interests.

Introduction: Visual function deficits have been reported in adolescents following concussion. We compared vergence and accommodation deficits in paediatric and adolescent patients at a tertiary medical centre in the sub-acute (15 days to 12 weeks) and chronic (12 weeks to 1 year) phases of concussion recovery., Methods: The study included patients aged 7 to <18 years seen between 2014 and 2021, who had a binocular vision (BV) examination conducted within 15 days and 1 year of their concussion injury. Included patients had to have 0.10 logMAR monocular best-corrected vision or better in both eyes and be wearing a habitual refractive correction. BV examinations at near included measurements of near point of convergence, convergence and divergence amplitudes, vergence facility, monocular accommodative amplitude and monocular accommodative facility. Vergence and accommodation deficits were diagnosed using established clinical criteria. Group differences were assessed using nonparametric statistics and ANCOVA modelling., Results: A total of 259 patients were included with 111 in the sub-acute phase and 148 in the chronic phase of concussion recovery. There was no significant difference in the rates of vergence deficits between the two phases of concussion recovery (sub-acute = 48.6%; chronic = 49.3%). There was also no significant difference in the rates of accommodation deficits between the two phases of concussion recovery (sub-acute = 82.0%; chronic = 77.0%)., Conclusion: Patients in both the sub-acute and chronic phases of concussion recovery exhibited a high frequency of vergence and accommodation deficits, with no significant differences between groups. Results indicate that patients exhibiting vision deficits in the sub-acute phase may not resolve without intervention, though a prospective, longitudinal study is required to test the hypothesis., (© 2024 College of Optometrists.)

Background and Objectives: The consensus criteria for traumatic encephalopathy syndrome (TES), the possible in vivo clinical syndrome associated with significant repetitive head impacts, have only been minimally studied to date. This study examined the prevalence of the proposed core clinical features of TES in a sample of healthy adults., Methods: A cross-sectional survey study was conducted through ResearchMatch, a national health volunteer registry. Participants were assessed for symptoms of TES based on the 2021 consensus criteria, including prior repetitive head impacts and core clinical features. Additional health information (e.g., concussion history, psychological health, sleep, chronic pain) was also evaluated. The consensus proposed research criteria for TES (i.e., reporting at least one progressive core clinical feature of TES, as in progressive difficulties with episodic memory, executive functioning, or neurobehavioral dysregulation) were applied to the sample., Results: Out of 1100 participants (average age = 53.6 ± 17.7 years, 55% women), 34.6% endorsed one or more progressive core clinical features of TES. Participants with a significant history of contact sports (i.e., ≥ 5 years total, with ≥ 2 years in high school or beyond) had similar rates of endorsing a progressive core clinical feature of TES compared to those without significant histories of repetitive head impacts (36.4% vs 32.8%, respectively, χ 2  = 0.52, p = 0.47). A significant history of repetitive head impacts in sports was not associated with endorsing a core clinical feature of TES in univariable or multivariable models (p > 0.47), whereas current depression/anxiety (odds ratio [OR] = 6.94), a history of psychiatric disorders (OR = 2.57), current sleep problems (OR = 1.56), and younger age (OR = 0.99) were significant predictors of TES status in a multivariable model. In a subsample of 541 participants who denied a lifetime history of contact sports, other forms of repetitive head impacts, and concussions, approximately 31.0% endorsed one or more progressive core clinical features of TES. Additionally, 73.5% of neurotrauma-naïve participants with current anxiety or depression reported at least one core progressive feature of TES, compared with 20.2% of those without clinically significant depression/anxiety symptoms., Conclusions: A considerable proportion of adults without a significant history of repetitive head impacts from sports endorsed core TES features, particularly those experiencing mental health symptoms. Having a significant history of contact sports was not associated with endorsing a core progressive clinical feature of TES, whereas other health factors were. These findings underscore the need for validating and refining TES criteria in samples with and without substantial neurotrauma histories., (© 2024. The Author(s).)

Objective: Despite the high prevalence, mild traumatic brain injury (mTBI)-induced chronic headache and cognitive deficits are poorly understood and lack effective treatments. Low-dose interleukin-2 (LD-IL-2) treatment soon after mTBI or overexpressing IL-2 in brain astrocytes prior to injury protects mice from developing post-traumatic headache (PTH)-related behaviors and cognitive decline. The present study addresses a clinically relevant knowledge gap: whether LD-IL-2 treatment long after the initial injury is still effective for chronic PTH and cognitive deficits., Methods: mTBI was induced by a noninvasive closed-head weight drop method. LD-IL-2 was administered 4-6 weeks post-mTBI to assess its effects on chronic PTH-related facial mechanical hypersensitivity as well as mTBI-induced impairment in novel object recognition and object location tests. Endogenous regulatory T (Treg) cells were depleted to investigate the mechanism of action of LD-IL-2., Results: Delayed LD-IL-2 treatment abolished chronic PTH-related behaviors. It also completely reversed mTBI-induced cognitive impairment in both male and female mice. Treg cell depletion not only prolonged PTH-related behaviors but also abolished the effects of LD-IL-2. Interestingly, LD-IL-2 treatment significantly increased the number of Treg cells in dura but not in brain tissues., Interpretation: These results suggest that the beneficial effects of LD-IL-2 treatment are mediated through the expansion of meningeal Treg cells. Collectively, our study identifies Treg as a cellular target and LD-IL-2 as a promising therapy for both chronic PTH and mTBI-induced cognitive impairment for both males and females, with a wide therapeutic time window and the potential of reducing polypharmacy in mTBI treatment. ANN NEUROL 2024;96:508-525., (© 2024 American Neurological Association.)

Objectives: To quantify norms and changes in eye-tracking proficiency, and determine vestibular symptom correlations in varsity college athletes following acute mild traumatic brain injury (mTBI). We hypothesized that mTBI impacts central coordination between the vestibular and oculomotor systems with resultant changes in eye-tracking proficiency that are correlated with vestibular symptom provocation., Design: Retrospective cohort study., Setting: Sports medicine care at a single institution., Patients: One hundred and nineteen college athletes diagnosed with mTBI by a physician between 2013 and 2019., Interventions: N/A., Main Outcome Measures: Standard deviation of tangential error, standard deviation of radian error, mean phase error, and horizontal gain from virtual reality-based, circular eye-tracking goggles used at baseline and within 72 hours post-mTBI. Headache, dizziness, nausea, and fogginess provocation after the Vestibular Ocular Motor Screening (VOMS) smooth pursuits subtest compared with pretest baseline, assessed within 72 hours post-mTBI., Results: One hundred and nineteen college athletes (N = 56 women and 63 men) aged 18 to 24 years sustained a total of 177 mTBI. Forty-four percent of athletes displayed abnormal eye-tracking on at least 1 eye-tracking measure following acute mTBI compared with their baseline. From the VOMS, horizontal gain showed medium-sized to large-sized positive correlations with headache ( r = 0.34) and dizziness ( r = 0.54), respectively. Mean phase error showed a medium-sized negative correlation with nausea ( r = -0.32) on the VOMS., Conclusions: Eye-tracking proficiency was impaired and correlated with vestibular symptom provocation following acute mTBI in college athletes. Future research should examine eye-tracking proficiency testing in other acute care settings to support mTBI diagnosis., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Self-reported histories of mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) symptoms are prevalent among post-9/11 veterans. Both are associated with subjective and often overlapping symptom complaints, but variably with objective neuropsychological test performances. These outcomes are seldom explored in relation to lifetime mTBI burden. This cross-sectional study examined associations of PTSD and lifetime mTBI with subjective (persistent symptoms after concussion and cognitive complaints) and objective (performances across five cognitive domains) measures among 46 veterans. Within this sample, 20 veterans had Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) confirmed PTSD (PTSD+), whereas 26 demographically-similar participants did not meet criteria (PTSD-). The Boston Assessment of Traumatic Brain Injury-Lifetime (BAT-L) yielded total mTBI scores ranging from 0 to 8. Regressions showed PTSD was associated with increased subjective symptoms/cognitive complaints, along with reduced verbal fluency, visuospatial memory, and processing speed performances. Lifetime mTBI burden was associated with subjective symptoms, but not with objective cognitive test performance, after controlling for PTSD. No significant interactions were observed. Exploratory correlations suggested that all PTSD symptom clusters were generally associated with the subjective and objective measures. However, fewer significant associations emerged within the PTSD+/- groups separately, with each group yielding somewhat different patterns of relationships. PTSD and increasing mTBI burden are consistently associated with negative subjective symptoms, including cognitive complaints. Each condition likely explains some degree of unique variance in symptom reporting. PTSD is associated with poorer objective cognition on some tasks, including processing speed, executive functioning, and learning/memory. Implications are explored.

Individuals with mild traumatic brain injury (mTBI) often complain of executive functioning (EF) difficulties. There is a discrepancy between self-reported EF impairment and EF deficits on neuropsychological tests, with some arguing that self-report EF is more related to real-world functioning than EF tests. However, research suggests that self-reported EF may be related more to emotional distress and is vulnerable to invalid reporting. We examined the vulnerability of the short form Barkley Deficits in Executive Functioning Scale (BDEFS) to invalid reporting, using a simulated mTBI paradigm. We included four groups: individuals simulating mTBI with (N = 24) and without (N = 21) histories of mTBI/other psychological conditions and controls with (N = 21) and without (N = 25) histories of mTBI/other psychological conditions. As hypothesized, simulators performed worse on the BDEFS Total Score and EF Symptom Count relative to controls; however, this effect was larger within those who had no self-reported history of mTBI/other psychological conditions. We identified a preliminary cutoff on the EF Symptom Count that detected 42.8% of simulators, with 95% specificity relative to the controls with histories of mTBI/other psychological conditions. The present study emphasizes the need for validity scales on self-report EF measures such as the BDEFS.

Objective: The authors examined the interaction between apolipoprotein E (APOE) ε4 and brain-derived neurotrophic factor (BDNF) Val66Met alleles on neuropsychological functioning among veterans with histories of mild traumatic brain injury (mTBI)., Methods: Participants were 78 veterans with mTBI (85% males; mean±SD age=32.95±7.00 years; mean time since injury=67.97±34.98 months) who completed a structured clinical interview and underwent a comprehensive neuropsychological assessment. Participants also provided a buccal swab for determination of their APOE and BDNF genotypes. Three cognitive composite scores were calculated from the neuropsychological assessment, reflecting visuospatial speed (seven variables), executive functioning (10 variables), and memory (eight variables). Two-way analyses of covariance (ANCOVAs) adjusted for age, sex, and race-ethnicity were used to assess the effects of APOE (ε4+ vs. ε4-) and BDNF (Met+ vs. Met-) on cognitive functioning., Results: ANCOVAs revealed no significant main effects of APOE or BDNF genotypes on cognitive functioning; however, there was a significant APOE-by-BDNF genotype interaction for all three cognitive composite measures (visuospatial speed: η p 2 =0.055; executive functioning: η p 2 =0.064; and memory: η p 2 =0.068). Specifically, the ε4+/Met+ (N=8) subgroup demonstrated the poorest cognitive functioning relative to all other allele subgroups (ε4+/Met-: N=12, ε4-/Met+: N=23, and ε4-/Met-: N=35)., Conclusions: This exploratory study is the first to show that, compared with other allele subgroups assessed, veterans with both ε4 and Met alleles demonstrated the poorest cognitive functioning across several cognitive domains known to be negatively affected in the context of mTBI. Further research with larger sample sizes is needed to replicate these findings., Competing Interests: This article does not necessarily represent the views of the VA or the U.S. government.

Objectives: Traumatic brain injury (TBI) is associated with sleep deficits, but it is not clear why some report sleep disturbances and others do not. The objective of this study was to assess the associations between axonal injury, sleep, and memory in chronic and acute TBI., Methods: Data were acquired from two independent datasets which included 156 older adult veterans (69.8 years) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) with prior moderate-to-severe TBIs and 90 (69.2 years) controls and 374 (39.6 years) from Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) with a recent mild TBI (mTBI) and 87 controls (39.6 years), all who completed an MRI, memory assessment, and sleep questionnaire., Results: Older adults with a prior TBI had a significant association between axonal injury and sleep disturbances [β = 9.52, 95% CI (4.1, 14.9), p = 0.01]. Axonal injury predicted changes in memory over 1-year in TBI [β = -8.72, 95% CI (-18, -2.7), p = 0.03]. We externally validated those findings in TRACK-TBI where axonal injury within 2 weeks after mTBI was significantly associated with higher sleep disturbances in the TBI group at 2 weeks[β = -7.2, 95% CI (-14, -0.50), p = 0.04], 6 months [β = -16, 95% CI (-24, -7.6), p ≤ 0.01], and 12 months post-injury [β = -11, 95% CI (-19, -0.85), p = 0.03]. These associations were not significant in controls., Interpretations: Axonal injury, specifically to the left anterior internal capsule is robustly associated with sleep disturbances in multiple TBI populations. Early assessment of axonal injury following mTBI could identify those at risk for persistent sleep disturbances following injury., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)