Temporal expression of brainstem neurotrophic proteins following mild traumatic brain injury.

BDNF, a neurotrophic factor, and its receptors have been implicated in the pathophysiology of mild traumatic brain injury (mTBI). The brainstem houses many vital functions, that are also associated with signs and symptoms of mTBI, but has been understudied in mTBI animal models. We determined the extent to which neurotrophic protein and associated receptor expression is affected within the brainstem of adult rats following mTBI. Their behavioral function was assessed and temporal expression of the 'negative' regulators of neuronal function (p75, t-TrkB, and pro-BDNF) and 'positive' neuroprotective (FL-TrkB and m-BDNF) protein isoforms were determined via western blot and immunohistochemistry at 1, 3, 7, and 14 post-injury days (PID) following mTBI or sham (control) procedure. Within the brainstem, p75 expression increased at PID 1 vs. sham animals. t-TrkB and pro-BDNF expression increased at PID 7 and 14. The 'positive' protein isoforms of FL-TrkB and m-BDNF expression were increased only at PID 7. The ratio of t-TrkB:FL-TrkB (negative:positive) was substantial across groups and time points, suggesting a negative impact of neurotrophic signaling on neuronal function. Additional NeuN experiments revealed cell death occurring within a subset of neurons within the medulla. While behavioral measures improved by PID 7-14, negative neurotrophic biochemical responses persisted. Despite the assertion that mTBI produces "mild" injury, evidence of cell death was observed in the medulla. Ratios of TrkB and BDNF isoforms with conflicting functions suggest that future work should specifically measure each subtype since they induce opposing downstream effects on neuronal function.

An Exploratory Analysis of Physical Examination Subtypes in Pediatric Athletes With Concussion.

OBJECTIVE: Pediatric athletes with concussion present with a variety of impairments on clinical assessment and require individualized treatment. The Buffalo Concussion Physical Examination is a brief, pertinent clinical assessment for individuals with concussion. The purpose of this study was to identify physical examination subtypes in pediatric athletes with concussion within 2 weeks of injury that are relevant to diagnosis and treatment. DESIGN: Secondary analysis of a published cohort study and clinician consensus. SETTING: Three university-affiliated sports medicine centers. PARTICIPANTS: Two hundred seventy children (14.9 ± 1.9 years). INDEPENDENT VARIABLES: Orthostatic intolerance, horizontal and vertical saccades, smooth pursuits, vestibulo-ocular reflex, near-point convergence, complex tandem gait, neck range of motion, neck tenderness, and neck spasm. MAIN OUTCOME MEASURES: Correlations between independent variables were calculated, and network graphs were made. k-means and hierarchical clustering were used to identify clusters of impairments. Optimal number of clusters was assessed. Results were reviewed by experienced clinicians and consensus was reached on proposed subtypes. RESULTS: Physical examination clusters overlapped with each other, and no optimal number of clusters was identified. Clinician consensus suggested 3 possible subtypes: (1) visio-vestibular (horizontal and vertical saccades, smooth pursuits, and vestibulo-ocular reflex), (2) cervicogenic (neck range of motion and spasm), and (3) autonomic/balance (orthostatic intolerance and complex tandem gait). CONCLUSIONS: Although we identified 3 physical examination subtypes, it seemed that physical examination findings alone are not enough to define subtypes that are both statistically supported and clinically relevant, likely because they do not include symptoms, assessment of mood or cognitive problems, or graded exertion testing.

Early Identification and Management of Cervical Impairments in Pediatric Patients With Concussion May Reduce Risk of Delayed Recovery.

OBJECTIVE: Previous research, including high-quality systematic reviews, has found that cervical injury, which often accompanies concussive head injury, can delay recovery from concussion. One pilot randomized controlled trial found that focused cervical assessment and appropriate intervention in children and young adults with persisting postconcussive symptoms (PPCS) improved recovery outcomes. Our sports medicine clinics adopted this approach early (within 2 weeks) in children (aged 10-18 years) after concussion. This study describes our clinical management protocol and compares the recovery trajectories in children after concussion with and without a concomitant cervical injury. DESIGN: Prospective cohort study. SETTING: Three university-affiliated outpatient sports medicine clinics from September 2016 to December 2019. PATIENTS: One-hundred thirty-four concussed children with cervical impairment (mean age 14.9 years, 65% male, and 6.2 days since concussion) were compared with 130 concussed children without cervical impairment (mean age 14.9 years, 57% male, and 6.0 days since concussion). INDEPENDENT VARIABLES: Examination findings related to the cervical spine (range of motion, cervical spasm, and cervical tenderness). MAIN OUTCOME MEASURES: Recovery time (measured in days), concussion symptom burden (Postconcussion Symptom Scale), and incidence of PPCS. RESULTS: Children with cervical impairment reported a higher initial symptom burden; however, there were no differences in recovery time (33.65 [28.20-39.09] days vs 35.98 [27.50-44.45] days, P = 0.651) or incidence of PPCS (40.0% vs 34.3%, P = 0.340). CONCLUSIONS: We conclude that within this pediatric population, early identification and management of cervical injuries concomitant with concussion may reduce the risk of delayed recovery.

Does Physiologic Post-Concussion Disorder Cause Persistent Post-Traumatic Headache?

PURPOSE OF REVIEW: One system classifies patients with symptoms after concussion into physiologic, vestibulo-ocular, cervicogenic, and mood/cognition post-concussion disorders (PCD) based upon the preponderance of specific symptoms and physical impairments. This review discusses physiologic PCD and its potential relationship to the development of persistent post-traumatic headaches (PPTH). RECENT FINDINGS: Headache is the most reported symptom after a concussion. Headaches in physiologic PCD are suspected to be due to abnormal cellular metabolism, subclinical neuroinflammation, and dysfunction of the autonomic nervous system (ANS). These abnormalities have been linked to the development of migraine-like and neuralgia-related PPTH. Physiologic PCD is a potential cause of PPTH after a concussion. Future research should focus on how to prevent PPTH in patients with physiologic PCD.

Sensitivity and Specificity of Exercise Intolerance on Graded Exertion Testing for Diagnosing Sport-Related Concussion: A Systematic Review and Exploratory Meta-Analysis.

Abstract There is no single gold standard test to diagnose sport-related concussion (SRC). Concussion-related exercise intolerance, that is, inability to exercise to the individual's appropriate level due to exacerbation of concussion-like symptoms, is a frequent finding in athletes early after SRC that has not been systematically evaluated as a diagnostic test of SRC. We performed a systematic review and proportional meta-analysis of studies that evaluated graded exertion testing in athletes after SRC. We also included studies of exertion testing in healthy athletic participants without SRC to assess specificity. Pubmed and Embase were searched in January 2022 for articles published since 2000. Eligible studies included those that performed graded exercise tolerance tests in symptomatic concussed participants (> 90% of subjects had an SRC, seen within 14 days of injury), at the time of clinical recovery from SRC, in healthy athletes, or both. Study quality was assessed using the Newcastle-Ottawa Scale. Twelve articles met inclusion criteria, most of which were of poor methodological quality. The pooled estimate of incidence of exercise intolerance in participants with SRC equated to an estimated sensitivity of 94.4% (95% confidence interval [CI]: 90.8, 97.2). The pooled estimate of incidence of exercise intolerance in participants without SRC equated to an estimated specificity of 94.6% (95% CI: 91.1, 97.3). The results suggest that exercise intolerance measured on systematic testing within 2 weeks of SRC may have excellent sensitivity for helping to rule in the diagnosis of SRC and excellent specificity for helping to rule out SRC. A prospective validation study to determine the sensitivity and specificity of exercise intolerance on graded exertion testing for diagnosing SRC after head injury as the source of symptoms is warranted.

Adults are not older adolescents: comparing physical therapy findings among adolescents, young adults and older adults with persistent post-concussive symptoms.

OBJECTIVE: Individuals with persistent post-concussive symptoms (PPCS) may present with a myriad of physical symptoms. There is limited research available comparing the presence of examination findings among individuals with PPCS from different age groups. METHODS: Retrospective case-control chart review of 481 patients with PPCS and 271 non-trauma controls. Physical assessments were categorized as ocular, cervical, and vestibular/balance. Differences in presentation were compared between PPCS and controls as well as between individuals with PPCS in three age groups: adolescents, young adults, and older adults. RESULTS: All three PPCS groups had more abnormal oculomotor findings than their age-matched counterparts. When comparing PPCS patients from different age groups, no differences were seen in prevalence of abnormal smooth pursuits or saccades; however, adolescents with PPCS had more abnormal cervical findings and a lower prevalence of abnormal NPC, vestibular and balance findings. CONCLUSION: Patients with PPCS presented with a different constellation of clinical findings based on their age. Adolescents were more likely to demonstrate evidence of cervical injury compared to younger and older adults, and adults were more likely to present with vestibular findings and impaired NPC. Adults with PPCS were more likely to present with abnormal oculomotor findings compared to adults with non-traumatic causes of dizziness.

Adolescents With More Oculomotor and Vestibular Signs of Sport-Related Concussion Benefit from Aerobic Exercise: An Exploratory Analysis.

Abstract Early targeted heart rate (HR) aerobic exercise has been shown to reduce the duration of recovery from sport-related concussion (SRC) as well as the incidence of persistent post-concussive symptoms (PPCS). It is not known, however, if more severe oculomotor and vestibular presentations of SRC benefit from a prescription of aerobic exercise. The current study is an exploratory analysis of two published randomized controlled trials that compared aerobic exercise within 10 days of injury with a placebo-like stretching intervention. Combining the two studies yielded a larger sample size to stratify severity of concussion based on the number of abnormal physical examination signs present at the initial office evaluation, which were confirmed with self-reported symptoms and recovery outcomes. The most discriminant cut-off was between those who had ≤3 oculomotor and vestibular signs and those who had >3 signs. Aerobic exercise (hazard ratio = 0.621 [0.412, 0.936], p = 0.023) reduced recovery times even when controlling for site (hazard ratio = 0.461 [0.303, 0.701], p < 0.001), severity (hazard ratio = 0.528 [0.325, 0.858], p = 0.010) and the interaction term of intervention and severity (hazard ratio = 0.972 [0.495, 1.909], p = 0.935). Adolescents who presented with >3 signs and were assigned to the placebo-like stretching group had a PPCS incidence of 38%, which was the highest of all subgroups (aerobic exercise and ≤3 findings: 8%; stretching and ≤3 findings: 11%; aerobic exercise and >3 findings: 21%). This exploratory study provides pilot evidence that prescribed sub-symptom threshold aerobic exercise treatment early after SRC may be effective for adolescents with more oculomotor and vestibular physical examination signs and should be validated in future adequately powered trials.

Service Delivery Models for the Management of Pediatric and Adolescent Concussion: A Systematic Review.

Objective: To examine the current peer-reviewed literature on pediatric concussion and mild traumatic brain injury (mTBI) service delivery models (SDMs) and relevant cost analyses. Data Sources: PubMed, Embase (Elsevier), CINAHL Plus (EBSCO), APA PsycINFO (EBSCO), and Web of Science Core Collection, limited to human trials published in English from January 1, 2001, to January 10, 2022. Study Selection: Included articles that (1) were peer-reviewed; (2) were evidence-based; (3) described service delivery and/or associated health care costs; and (4) focused on mTBI, concussion, or postconcussion symptoms of children and adolescents. Studies describing emergency department-based interventions, adults, and moderate to severe brain injuries were excluded. Data Extraction: The initial search resulted in 1668 articles. Using Rayyan software, 2 reviewers independently completed title and abstract screening followed by a full-text screening of potentially included articles. A third blinded reviewer resolved inclusion/exclusion conflicts among the other reviewers. This resulted in 28 articles included. Data Synthesis: Each of the 28 articles were grouped into 1 of the following 3 categories: generalist-based services (7), specialist-based services (12), and web/telemedicine services (6). One article discussed both generalists and specialists. It was clear that specialists are more proactive in their treatment of concussion than generalists. Most of the research on generalists emphasized the need for education and training. Four studies discussed costs relevant to SDMs. Conclusions: This review highlights the need for more discussion and formalized evaluation of SDMs to better understand concussion management. Overall there is more literature on specialist-based services than generalist-based services. Specialists and generalists have overarching similarities but differ often in their approach to pediatric concussion management. Cost analysis data are sparse and more research is needed.

Practical Management: Telehealth Examination for Sport-Related Concussion in the Outpatient Setting.

ABSTRACT: This article presents the telehealth version of the Buffalo Concussion Physical Examination (BCPE) (Tele-BCPE). It is a brief, focused telehealth PE for use in the outpatient setting by sports medicine physicians, pediatricians, neurologists, and primary care physicians. It is derived from the BCPE and includes general considerations for providers performing telehealth services and instructions for adapting traditional clinical tests for virtual use. The Tele-BCPE includes an orthostatic intolerance screen, examination of the cranial nerves, and tests of the oculomotor, vestibular, and cervical systems. It is meant to be used at initial and follow-up outpatient visits for patients acutely after concussion and in those with prolonged symptoms. This telehealth PE, when combined with other assessments, can help provide direct treatment to patients at any stage after concussion and reduce barriers to healthcare access posed by the COVID-19 pandemic and for patients living in rural or underserved areas.

Development of a Telehealth Examination for Sport-Related Concussion in the Outpatient Setting.

OBJECTIVE: To develop a brief, focused telehealth physical examination for use in the outpatient setting by sports medicine physicians, pediatricians, neurologists, and primary care physicians. BACKGROUND: Telemedicine has become a key resource for addressing healthcare access limitations for individuals living in rural communities. The COVID-19 pandemic has forced physicians and other healthcare providers to adopt telemedicine practices. Published literature guiding the evaluation of patients with concussion via telemedicine is sparse. DESIGN/METHODS: The Buffalo Concussion Physical Examination (BCPE) is a practical and pertinent clinical assessment that helps to diagnose concussion and that has prognostic value when repeated over the first weeks after injury. An interdisciplinary team with experience in telemedicine services utilized a modified-Glaser approach to consensus to translate elements of the BCPE into virtual methods enabling clinicians to provide care to patients over the internet. RESULTS: The Telehealth version of the BCPE (Tele-BCPE) includes an orthostatic intolerance screen, examination of the cranial nerves, and tests of the oculomotor, vestibular and cervical systems. History and examination templates as well as detailed instructions for performance are included. The Tele-BCPE is meant to be used at initial and follow-up visits for patients acutely after concussion as well as in those with prolonged symptoms. CONCLUSIONS: We developed a telehealth physical examination to help direct treatment to patients at any stage after concussion and reduce barriers to healthcare access posed by the COVID-19 pandemic and for patients living in rural or underserved areas. Prospective evaluation of the validity and reliability of the Tele-BCPE for the diagnosis and management of patients with concussion is warranted.

Management of Concussion and Persistent Post-Concussive Symptoms for Neurologists.

PURPOSE OF REVIEW: Concussion is a complex injury that may present as a variety of clinical profiles, which can overlap and reinforce one another. This review summarizes the medical management of patients with concussion and persistent post-concussive symptoms (PPCS). RECENT FINDINGS: Management of concussion and PPCS relies on identifying underlying symptom generators. Treatment options include sub-symptom threshold aerobic exercise, cervical physical therapy, vestibular therapy, vision therapy, cognitive rehabilitation, cognitive behavioral therapy, pharmacological management, or a combination of treatments. Evidence-based treatments have emerged to treat post-concussion symptom generators for sport-related concussion and for patients with PPCS.

Clinical Assessment of Concussion and Persistent Post-Concussive Symptoms for Neurologists.

PURPOSE OF REVIEW: Concussion produces a variety of signs and symptoms. Most patients recover within 2-4 weeks, but a significant minority experiences persistent post-concussive symptoms (PPCS), some of which may be from associated cervical or persistent neurologic sub-system (e.g., vestibular) dysfunction. This review provides evidence-based information for a pertinent history and physical examination of patients with concussion. RECENT FINDINGS: The differential diagnosis of PPCS is based on the mechanism of injury, a thorough medical history and concussion-pertinent neurological and cervical physical examinations. The concussion physical examination focuses on elements of autonomic function, oculomotor and vestibular function, and the cervical spine. Abnormalities identified on physical examination can inform specific forms of rehabilitation to help speed recovery. Emerging data show that there are specific symptom generators after concussion that can be identified by a thorough history, a pertinent physical examination, and adjunct tests when indicated.

Traumatic brain injury among refugees and asylum seekers.

BACKGROUND: Refugees and asylum seekers face many challenges in their pursuit of a safe home. The journey for displaced individuals can be extremely dangerous and many do not survive or go missing. Survivors face significant risks of injury, abuse, and torture. Traumatic brain injury is one of the most common and disabling injuries sustained by these populations. This already complex condition can have profound implications on these groups and their families due to factors related to mental health, cultural perspectives, and their ability to navigate healthcare systems. METHODS: A literature review was performed to investigate the incidence and prevalence of torture and traumatic brain injury in displaced and fleeing populations. Impacts of traumatic brain injury and residency status on outcomes in these individuals were also examined. RESULTS: The incidence and prevalence of torture and traumatic brain injury among refugees and asylum seekers is significant. These populations may access healthcare systems differently than other groups and as a result may experience a unique health-related outcomes following traumatic brain injury. CONCLUSIONS: This information should sensitize healthcare providers to a potential history of traumatic brain injury sustained by patients/clients who are refugees or asylum seekers and may serve to guide some clinical encounters. Implications for rehabilitation Traumatic brain injuries are commonly sustained by refugees and asylum seekers. Cultural factors may complicate how refugees and asylum seekers understand, report, and manage these injuries. The above may be worsened by cognitive, emotional, and behavioral changes following traumatic brain injury. Rehabilitation providers should be aware of potential traumatic brain injury history during encounters with refugee and asylum seeker populations, especially if a history of torture is suspected.