Impact of Playing Surface on Concussion Symptoms in Young American Football Players.

OBJECTIVE: It has been suggested that sport-related concussion (SRC) occurs more commonly on natural grass compared with artificial turf in contact sports. As playing surface is a potentially modifiable risk factor, this study sought to identify differences in symptoms following SRC on these 2 surfaces in a sample of young American football players. DESIGN: Prospective. SETTING: Part of the multi-institutional North Texas Concussion Registry (ConTex) research project. PARTICIPANTS: Ten-year-old to 24-year-old male American football players (n = 62) who had sustained a helmet-to-ground SRC and presented to a specialty concussion clinic within 14 days of injury. INDEPENDENT VARIABLES: Helmeted impact with grass (n = 33) or artificial turf (n = 29). MAIN OUTCOME MEASURES: Severity and number of symptoms endorsed on the Sport Concussion Assessment Tool 5th Edition (SCAT5) Symptom Evaluation at the time of initial clinical evaluation. RESULTS: Both groups were similar in mean time since injury, concussion history, and history of headache, but the artificial turf group was slightly older, with a mean age of 14.6 versus 13.6 years ( P = 0.039). Athletes who sustained a SRC on grass reported significantly higher mean total symptom severity scores (26.6 vs 11.6, P = 0.005) and total number of symptoms (10.3 vs 5.9, P = 0.006) compared with those who were injured on artificial turf. CONCLUSIONS: This may be the first study to examine postconcussive symptoms after SRC as they relate to playing surface. This small sample of young American football players reported higher symptom severity scores and higher total number of symptoms after SRC on natural grass compared with artificial turf.

Post-Traumatic Gliomas in Adults: Review of the Case Reports and Studies.

Traumatic brain injury (TBI) was first proposed as a potential risk factor for developing a glioma in the 1800s, and conditions for establishing a causal relationship between brain injury and gliomas have since been proposed. Given the medical and legal ramifications, the current literature was reviewed to better understand this possible association. Articles that examined the relationship between TBI and glioma formation in adults and were published in English between 1978 and 2022 were reviewed. There were 19 case reports of 25 patients and 16 observational studies. The case reports describe glioma formation at the precise site of prior brain injury in continuity with traumatic scar; the observational studies report conflicting findings, but they largely demonstrate no association. Most of the observational studies are limited by their retrospective nature, but we identified one prospective cohort study which found a positive association. Altogether, we suggest that glioma formation after TBI is a rare occurrence that warrants further study.

Characterisation of TRIM46 autoantibody-associated paraneoplastic neurological syndrome.

OBJECTIVES: To report the expanded neurological presentations and oncological associations of tripartite motif-containing protein 46 (TRIM46)-IgG seropositive patients. METHODS: Archived sera/cerebrospinal fluid (CSF) were evaluated by tissue-based immunofluorescence assay to identify patients with identical axon initial segment (AIS)-specific staining pattern. Phage immunoprecipitation sequencing (PhIP-Seq) was used to identify the putative autoantigen. RESULTS: IgG in serum (17) and/or CSF (16) from 25 patients yielded unique AIS-specific staining on murine central nervous system (CNS) tissue. An autoantibody specific for TRIM46 was identified by PhIP-Seq, and autoantigen specificity was confirmed by transfected COS7 cell-based assay. Clinical information was available for 22 TRIM46-IgG seropositive patients. Fifteen were female (68%). Median age was 67 years (range 25-87). Fifteen (68%) patients presented with subacute cerebellar syndrome (six isolated; nine with CNS accompaniments: encephalopathy (three), brainstem signs (two), myelopathy (two), parkinsonism (one)). Other phenotypes included limbic encephalitis (three), encephalopathy with/without seizures (two), myelopathy (two). Eighteen (82%) had cancer: neuroendocrine carcinomas (9; pancreatic (3), small-cell lung (4), oesophagus (1), endometrium (1)), adenocarcinomas (6; lung (2), ovarian (2), endometrial (1), breast (1)), sarcoma (2) and gastrointestinal tumour (1). Neurological symptoms in three followed immune checkpoint inhibitor (ICI) administration. CONCLUSIONS: This study supports TRIM46-IgG being a biomarker of paraneoplastic CNS disorders and expands the neurological phenotypes, oncological and ICI-related adverse event associations.

Posttraumatic Headache.

Posttraumatic headache (PTH) is the most common secondary headache disorder, accounting for approximately 4% of all headache disorders. It is the most common symptom following concussion (mild traumatic brain injury) and can be debilitating for many who have persistent symptoms. With a recent increase in public awareness regarding traumatic brain injury, there has been a corresponding increase in PTH research. The pathophysiology of PTH remains poorly understood and the underlying mechanisms are likely multifactorial. Diagnosis of PTH is dependent on a temporal relationship to a head injury. PTH often resembles common primary headache phenotypes. Treatment of PTH utilizes known treatments for these other headache phenotypes, as there is no currently approved treatment specifically for PTH. Moving forward, further studies are needed to better define and validate the definition of PTH, understand the underlying pathophysiology, and find more specific treatments.

Active duty service members who sustain a traumatic brain injury have chronically elevated peripheral concentrations of Aß40 and lower ratios of Aß42/40.

PRIMARY OBJECTIVE: Excessive accumulation of amyloid beta (Aß) and tau have been observed in older individuals with chronic neurological symptoms related to a traumatic brain injury (TBI), yet little is known about the possible role of Aß in younger active duty service members following a TBI. The purpose of the study was to determine if Aß 40 or 42 related to sustaining a TBI or to chronic neurological symptoms in a young cohort of military personnel. RESEARCH DESIGN: This was a cross-sectional study of active duty service members who reported sustaining a TBI and provided self-report of neurological and psychological symptoms and provided blood. METHODS AND PROCEDURES: An ultrasensitive single-molecule enzyme-linked immunosorbent assay was used to compare concentrations of Aß in active duty service members with (TBI+; n = 53) and without (TBI-; n = 18) a history of TBI. Self-report and medical history were used to measure TBI occurrence and approximate the number of total TBIs and the severity of TBIs sustained during deployment. MAIN OUTCOMES AND RESULTS: This study reports that TBI is associated with higher concentrations of Aß40 (F1,68 = 6.948, p = 0.009) and a lower ratio of Aß42/Aß40 (F1,62 = 5.671, p = 0.020). These differences remained significant after controlling for co-morbid symptoms of post-traumatic stress disorder and depression. CONCLUSIONS: These findings suggest that alterations in Aß relate to TBIs and may contribute to chronic neurological symptoms.

The National Football League Concussion Protocol: A Review.

Sport-related concussion remains an area of high concern for contact sport athletes and their families, as well as for the medical and scientific communities. The National Football League (NFL), along with the NFL Players Association and experts in the field, has developed protocols for the detection and management of sport-related concussions. This article reviews the NFL's most recent concussion protocol including preseason education and baseline testing for players, concussion surveillance by gameday medical teams and neurotrauma consultants and athletic trainers, gameday concussion protocol and procedures, and return to participation guidelines.

Sex differences in reporting of concussion symptoms in adults.

Objective: To examine differences in concussion symptom reporting between female and male adults considering current psychological symptoms such as anxiety and depression and pre-injury factors in order to identify sex differences which may guide treatment efforts. Method: This prospective study is part of the North Texas Concussion Registry (ConTex). Subjects (N = 132) age 19 to 78 years had sustained a concussion within 30 days of clinic visit. The independent variable was sex and covariates included age, ethnicity, current anxiety and depression ratings, history of attention deficit disorder, history of headache/migraine, and time to clinic. The dependent variables were 22 post-concussion symptoms as measured by the Sport Concussion Assessment Tool-5 Post-Concussion Symptom Scale. Results: Analysis of covariance and ordinal logistic regression results both revealed that females had a greater likelihood of reporting increased symptom severity for 15/22 concussion symptoms. The largest risk ratios (effect size) in symptom reporting between sexes (higher symptoms in females) included: feeling more emotional 4.05 (0.72), fatigue or low energy 4.05 (0.72), sensitivity to light 3.74 (0.69), headache 3.65 (0.57), balance problems 3.31 (0.53), pressure in head 3.06 (0.51), and neck pain 2.97 (0.60). Conclusions: Adult females in our sample reported higher levels of many concussion symptoms than males and showed an increased risk of developing these same symptoms following concussion. Examination of the magnitude of sex difference in concussion symptom reporting will better inform medical staff to anticipate and address symptoms that may present greater challenges for adult females.

Lower health related quality of life in U.S. military personnel is associated with service-related disorders and inflammation.

Military personnel who have combat exposures are at increased risk for the service-related disorders of post-traumatic stress disorder (PTSD), depression, sleep disturbances and decreased health related quality of life (HRQOL). Those with a traumatic brain injury (TBI) are at even greater risk. Inflammation is associated with these disorders and may underlie the risk for health declines. We evaluated 110 recently deployed, military personnel presenting with sleep disturbances for service-related disorders (TBI, PTSD, and depression) as well as HRQOL. ANOVA models were used to examine differences among military personnel with two or more service-related disorders (high comorbid group), or one or no disorders (low comorbid group). Logistic regression models were used to determine associations among interleukin-6 (IL-6) to HRQOL and service-related disorders. Approximately one-third of the sample had two or more service-related disorders. HRQOL was lower and IL-6 concentrations were higher in military personnel with PTSD or depression, with the most profound differences in those with more service-related disorders, regardless of sleep disorder. Having symptoms of depression and PTSD resulted in a 3.5-fold risk to be in the lower quartile of HRQOL and the highest quartile of IL-6. In a linear regression model, 41% of the relationship between HRQOL and IL-6 concentrations was mediated by PTSD and depression. Military personnel with PTSD and depression are at high risk for lower HRQOL, and higher IL-6 concentrations. Comprehensive treatment is required to address co-occurring service-related disorders in military personnel to promote health and well-being.

Sleep restoration is associated with reduced plasma C-reactive protein and depression symptoms in military personnel with sleep disturbance after deployment.

BACKGROUND: Deployed military personnel are vulnerable to chronic sleep disturbance, which is highly comorbid with post-traumatic stress disorder (PTSD) and depression, as well as declines in health-related quality of life (HRQOL). Inflammation is associated with HRQOL declines and sleep-related comorbidities; however, the impact of sleep changes on comorbid symptoms and inflammation in this population is unknown. METHODS: In this observational study, we examined the relationship between reported sleep changes and concentrations of inflammatory biomarkers, interleukin 6 (IL-6), and C-reactive protein (CRP) in peripheral blood. The sample was dichotomized into two groups: (1) decrease in Pittsburgh Sleep Quality Index (PSQI; restorative sleep) and (2) no change or increase in PSQI (no change). Mixed between-within subjects analysis of variance tests were used to determine group differences on changes of inflammation and comorbid symptoms. RESULTS: In our sample of 66 recently deployed military personnel with insomnia, 34 participants reported restorative sleep whereas 32 reported no sleep changes. The two groups did not differ in demographic or clinical characteristics, with the exception of PTSD diagnosis at baseline. The restorative sleep group had significant reductions in CRP concentrations and depression symptoms, as well as reduced fatigue and improvements in emotional well-being, social functioning, and physical functioning at follow-up. CONCLUSIONS: Military personnel who report sleep restoration after deployment have reduced CRP concentrations, decreased severity of depression, and improved HRQOL. These findings suggest that treatment for sleep disturbances may be associated with improvements in mental and physical health, thereby supporting continued study in this line of research.

Military personnel with chronic symptoms following blast traumatic brain injury have differential expression of neuronal recovery and epidermal growth factor receptor genes.

OBJECTIVE: Approximately one-quarter of military personnel who deployed to combat stations sustained one or more blast-related, closed-head injuries. Blast injuries result from the detonation of an explosive device. The mechanisms associated with blast exposure that give rise to traumatic brain injury (TBI), and place military personnel at high risk for chronic symptoms of post-concussive disorder (PCD), post-traumatic stress disorder (PTSD), and depression are not elucidated. METHODS: To investigate the mechanisms of persistent blast-related symptoms, we examined expression profiles of transcripts across the genome to determine the role of gene activity in chronic symptoms following blast-TBI. Active duty military personnel with (1) a medical record of a blast-TBI that occurred during deployment (n = 19) were compared to control participants without TBI (n = 17). Controls were matched to cases on demographic factors including age, gender, and race, and also in diagnoses of sleep disturbance, and symptoms of PTSD and depression. Due to the high number of PCD symptoms in the TBI+ group, we did not match on this variable. Using expression profiles of transcripts in microarray platform in peripheral samples of whole blood, significantly differentially expressed gene lists were generated. Statistical threshold is based on criteria of 1.5 magnitude fold-change (up or down) and p-values with multiple test correction (false discovery rate <0.05). RESULTS: There were 34 transcripts in 29 genes that were differentially regulated in blast-TBI participants compared to controls. Up-regulated genes included epithelial cell transforming sequence and zinc finger proteins, which are necessary for astrocyte differentiation following injury. Tensin-1, which has been implicated in neuronal recovery in pre-clinical TBI models, was down-regulated in blast-TBI participants. Protein ubiquitination genes, such as epidermal growth factor receptor, were also down-regulated and identified as the central regulators in the gene network determined by interaction pathway analysis. CONCLUSION: In this study, we identified a gene-expression pathway of delayed neuronal recovery in military personnel a blast-TBI and chronic symptoms. Future work is needed to determine if therapeutic agents that regulate these pathways may provide novel treatments for chronic blast-TBI-related symptoms.

Epigenetic Mechanisms Shape the Biological Response to Trauma and Risk for PTSD: A Critical Review.

Posttraumatic stress disorder (PTSD) develops in approximately one-quarter of trauma-exposed individuals, leading us and others to question the mechanisms underlying this heterogeneous response to trauma. We suggest that the reasons for the heterogeneity relate to a complex interaction between genes and the environment, shaping each individual's recovery trajectory based on both historical and trauma-specific variables. Epigenetic modifications provide a unique opportunity to elucidate how preexisting risk factors may contribute to PTSD risk through changes in the methylation of DNA. Preexisting risks for PTSD, including depression, stress, and trauma, result in differential DNA methylation of endocrine genes, which may then result in a different biological responses to trauma and subsequently a greater risk for PTSD onset. Although these relationships are complex and currently inadequately described, we provide a critical review of recent studies to examine how differences in genetic and proteomic biomarkers shape an individual's vulnerability to PTSD development, thereby contributing to a heterogeneous response to trauma.

A Framework to Examine the Role of Epigenetics in Health Disparities among Native Americans.

Background. Native Americans disproportionately experience adverse childhood experiences (ACEs) as well as health disparities, including high rates of posttraumatic stress, depression, and substance abuse. Many ACEs have been linked to methylation changes in genes that regulate the stress response, suggesting that these molecular changes may underlie the risk for psychiatric disorders related to ACEs. Methods. We reviewed published studies to provide evidence that ACE-related methylation changes contribute to health disparities in Native Americans. This framework may be adapted to understand how ACEs may result in health disparities in other racial/ethnic groups. Findings. Here we provide evidence that links ACEs to methylation differences in genes that regulate the stress response. Psychiatric disorders are also associated with methylation differences in endocrine, immune, and neurotransmitter genes that serve to regulate the stress response and are linked to psychiatric symptoms and medical morbidity. We provide evidence linking ACEs to these epigenetic modifications, suggesting that ACEs contribute to the vulnerability for developing psychiatric disorders in Native Americans. Conclusion. Additional studies are needed to better understand how ACEs contribute to health and well-being. These studies may inform future interventions to address these serious risks and promote the health and well-being of Native Americans.