Using machine learning to discover traumatic brain injury patient phenotypes: national concussion surveillance system Pilot.

OBJECTIVE: The objective is to determine whether unsupervised machine learning identifies traumatic brain injury (TBI) phenotypes with unique clinical profiles. METHODS: Pilot self-reported survey data of over 10,000 adults were collected from the Centers for Disease Control and Prevention (CDC)'s National Concussion Surveillance System (NCSS). Respondents who self-reported a head injury in the past 12 months (n = 1,364) were retained and queried for injury, outcome, and clinical characteristics. An unsupervised machine learning algorithm, partitioning around medoids (PAM), that employed Gower's dissimilarity matrix, was used to conduct a cluster analysis. RESULTS: PAM grouped respondents into five TBI clusters (phenotypes A-E). Phenotype C represented more clinically severe TBIs with a higher prevalence of symptoms and association with worse outcomes. When compared to individuals in Phenotype A, a group with few TBI-related symptoms, individuals in Phenotype C were more likely to undergo medical evaluation (odds ratio [OR] = 9.8, 95% confidence interval[CI] = 5.8-16.6), have symptoms that were not currently resolved or resolved in 8+ days (OR = 10.6, 95%CI = 6.2-18.1), and more likely to report at least moderate impact on social (OR = 54.7, 95%CI = 22.4-133.4) and work (OR = 25.4, 95%CI = 11.2-57.2) functioning. CONCLUSION: Machine learning can be used to classify patients into unique TBI phenotypes. Further research might examine the utility of such classifications in supporting clinical diagnosis and patient recovery for this complex health condition.

Acute Eye-Tracking Changes Correlated With Vestibular Symptom Provocation Following Mild Traumatic Brain Injury.

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.

The American Congress of Rehabilitation Medicine Diagnostic Criteria for Mild Traumatic Brain Injury.

OBJECTIVE: To develop new diagnostic criteria for mild traumatic brain injury (TBI) that are appropriate for use across the lifespan and in sports, civilian trauma, and military settings. DESIGN: Rapid evidence reviews on 12 clinical questions and Delphi method for expert consensus. PARTICIPANTS: The Mild Traumatic Brain Injury Task Force of the American Congress of Rehabilitation Medicine Brain Injury Special Interest Group convened a Working Group of 17 members and an external interdisciplinary expert panel of 32 clinician-scientists. Public stakeholder feedback was analyzed from 68 individuals and 23 organizations. RESULTS: The first 2 Delphi votes asked the expert panel to rate their agreement with both the diagnostic criteria for mild TBI and the supporting evidence statements. In the first round, 10 of 12 evidence statements reached consensus agreement. Revised evidence statements underwent a second round of expert panel voting, where consensus was achieved for all. For the diagnostic criteria, the final agreement rate, after the third vote, was 90.7%. Public stakeholder feedback was incorporated into the diagnostic criteria revision prior to the third expert panel vote. A terminology question was added to the third round of Delphi voting, where 30 of 32 (93.8%) expert panel members agreed that 'the diagnostic label 'concussion' may be used interchangeably with 'mild TBI' when neuroimaging is normal or not clinically indicated.' CONCLUSIONS: New diagnostic criteria for mild TBI were developed through an evidence review and expert consensus process. Having unified diagnostic criteria for mild TBI can improve the quality and consistency of mild TBI research and clinical care.

Neuroimaging for mild traumatic brain injury in children: cross-sectional study using national claims data.

BACKGROUND: Current guidelines recommend healthcare professionals avoid routine use of neuroimaging for diagnosing mild traumatic brain injury (mTBI). OBJECTIVE: This study aimed to examine current use of CT and MRI among children and young adult patients with mTBI and factors that increase likelihood of neuroimaging in this population. MATERIALS AND METHODS: Data were analyzed using the 2019 MarketScan commercial claims and encounters database for the commercially insured population for both inpatient and outpatient claims. Descriptive statistics and logistic regression models for patients ≤24 years of age who received an ICD-10-CM code indicative of a possible mTBI were analyzed. RESULTS: Neuroimaging was performed in 16.9% (CT; 95% CI=16.7-17.1) and 0.9% (MRI; 95% CI=0.8-0.9) of mTBI outpatient visits (including emergency department visits) among children (≤18 years old). Neuroimaging was performed in a higher percentage of outpatient visits for patients 19-24 years old (CT=47.1% [95% CI=46.5-47.6] and MRI=1.7% [95% CI=1.5-1.8]), and children aged 15-18 years old (CT=20.9% [95% CI=20.5-21.2] and MRI=1.4% [95% CI=1.3-1.5]). Outpatient visits for males were 1.22 (95% CI=1.10-1.25) times more likely to include CT compared to females, while there were no differences by sex for MRI or among inpatient stays. Urban residents, as compared to rural, were less likely to get CT in outpatient settings (adjusted odds ratio [aOR]=0.55, 95% CI=0.53-0.57). Rural residents demonstrated a larger proportion of inpatient admissions that had a CT. CONCLUSIONS: Despite recommendations to avoid routine use of neuroimaging for mTBI, neuroimaging remained common practice in 2019.

Multicentre evaluation of anxiety and mood among collegiate student athletes with concussion.

Objectives: Mental health problems are a premorbid and postinjury concern among college student athletes. Clinical phenotypes of anxiety and mood disruption are prevalent following mild traumatic brain injury, including concussion, a common sports injury. This work examined whether concussed student athletes with a history of mental health problems and higher symptoms of anxiety and mood disruption at baseline were more likely to have higher postinjury reports of mood and anxiety as well as prolonged resolution of postconcussive symptoms to near-baseline measures. Methods: This was a retrospective cohort study of a multi-institutional database of standardised baseline and postinjury assessments among college student athletes. Anxiety/mood evaluation data among varsity college athletes from four institutions over 1 year were measured and compared at baseline and postconcussion recovery using descriptive statistics and multilevel/mixed-effects analysis. Results: Data from 2248 student athletes were analysed, with 40.6% reporting at least one symptom of anxiety and/or mood disruption at baseline. Of the 150 distinct concussions, 94.7% reported symptoms of anxiety/mood disruption during recovery (recovery time=0-96 days). Higher anxiety/mood scores at baseline were significantly associated with higher scores following concussion (p<0.001). Recovery trajectories of anxiety/mood scores showed different patterns by sex and prolonged recovery. Conclusion: Symptoms of anxiety and mood disruption are common at baseline among college student athletes. These students are at higher risk for symptomatology following injury, representing a screening cohort that may benefit from early counselling. Almost all student athletes will experience symptoms of anxiety and/or mood disruption following concussion.

Firearm-Related Traumatic Brain Injury Homicides in the United States, 2000-2019.

BACKGROUND: Traumatic brain injury (TBI) is a leading cause of homicide-related death in the United States. Penetrating TBI associated with firearms is a unique injury with an exceptionally high mortality rate that requires specialized neurocritical trauma care. OBJECTIVE: To report incidence patterns of firearm-related and nonfirearm-related TBI homicides in the United States between 2000 and 2019 by demographic characteristics to provide foundational data for prevention and treatment strategies. METHODS: Data were obtained from multiple cause of death records from the National Vital Statistics System using Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research database for the years 2000 to 2019. Number, age-adjusted rates, and percent of firearm and nonfirearm-related TBI homicides by demographic characteristics were calculated. Temporal trends were also evaluated. RESULTS: During the study period, there were 77 602 firearm-related TBI homicides. Firearms were involved in the majority (68%) of all TBI homicides. Overall, men, people living in metro areas, and non-Hispanic Black persons had higher rates of firearm-related TBI homicides. The rate of nonfirearm-related TBI homicides declined by 40%, whereas the rate of firearm-related TBI homicides only declined by 3% during the study period. There was a notable increase in the rate of firearm-related TBI homicides from 2012/2013 through 2019 for women (20%) and nonmetro residents (39%). CONCLUSION: Firearm-related violence is an important public health problem and is associated with the majority of TBI homicide deaths in the United States. The findings from this study may be used to inform prevention and guide further research to improve treatment strategies directed at reducing TBI homicides involving firearms.

Rationale and Methods for Updated Guidelines for the Management of Penetrating Traumatic Brain Injury.

Penetrating traumatic brain injury (pTBI) affects civilian and military populations resulting in significant morbidity, mortality, and healthcare costs. No up-to-date and evidence-based guidelines exist to assist modern medical and surgical management of these complex injuries. A preliminary literature search revealed a need for updated guidelines, supported by the Brain Trauma Foundation. Methodologists experienced in TBI guidelines were recruited to support project development alongside two cochairs and a diverse steering committee. An expert multi-disciplinary workgroup was established and vetted to inform key clinical questions, to perform an evidence review and the development of recommendations relevant to pTBI. The methodological approach for the project was finalized. The development of up-to-date evidence- and consensus-based clinical care guidelines and algorithms for pTBI will provide critical guidance to care providers in the pre-hospital and emergent, medical, and surgical settings.

Risk of Concussion After a Targeting Foul in Collegiate American Football.

BACKGROUND: The targeting rule was adopted by the National Collegiate Athletic Association (NCAA) in 2008 to discourage dangerous contact during collegiate American football competition. Although targeting rules have been emphasized as a means to reduce concussion rates, there is currently no evidence that targeting plays are higher risk for concussion than other plays in American football. PURPOSE: To compare the rate of concussion occurring during targeting versus nontargeting plays in American collegiate football. STUDY DESIGN: Cross-sectional study. METHODS: Concussions occurring in games in the 2016-2019 Pac-12 Conference were classified as having occurred during either (1) a play where a targeting penalty was called or (2) all other plays. Targeting plays were further categorized to either those in which the call was upheld or those overturned by the on-field official after replay review. The number of targeting plays and the total number of plays during games were also recorded. Concussion incidence (per 1000 plays) and risk ratios were calculated. RESULTS: Overall, 538 games with 68,670 plays were reviewed, during which 213 concussions occurred (15 during plays where targeting was called and 198 on other plays) and 141 targeting penalties were called. The incidence of concussion was 106.4/1000 plays for targeting plays (including 141.2/1000 upheld targeting fouls and 53.6/1000 overturned targeting fouls) and 2.9/1000 plays for nontargeting plays. The risk of concussion during targeting plays was 36.9 (95% CI, 22.4-60.7) times greater than that for all other plays. The risk of concussion during targeting plays upheld was 49.0 (95% CI, 28.5-84.2) times greater than that for all other plays. CONCLUSION: Concussion risk was significantly higher during plays in which targeting was called, especially those in which targeting fouls were upheld. CLINICAL RELEVANCE: This study supports eliminating or reducing targeting from American football. The results of this study suggest that players should be screened for concussion after targeting plays are called.

Sex Differences in Common Measures of Concussion in College Athletes.

OBJECTIVE: Female athletes may be more likely to sustain a concussion and may vary in symptom presentation and neurocognitive impairments as compared with males. Scientific literature is limited by subjective assessments and underproportioned representation of women-the scope and etiology of sex-based differences are unknown. This study investigates sex-based differences in sports concussion assessments among college varsity athletes. DESIGN AND SETTING: Retrospective study of an institution's athletic head injury database. PARTICIPANTS: Acute postinjury and baseline data from 111 college athletes sustaining concussions between 2016 and 2018, diagnosed by a concussion specialist physician. MAIN OUTCOME MEASURES: Concussion assessments examined included the Sports Concussion Assessment Tool (SCAT5) and Vestibular Oculomotor Screening (VOMS) performed within 3 days (24-72 hours) of injury. RESULTS: No significant difference by sex was observed in the SCAT5 total symptom evaluation scores or severity scores, Standardized Assessment of Concussion, or Balance Error Scoring System ( P > .05) within 3 days of head injury. Females did report more "pressure in the head" severity scores from baseline to postconcussion (2.7 ± 1.5 increased symptomatology in females vs 1.8 ± 1.3 increase in males, P = .007). The VOMS test resulted in significant sex differences in smooth pursuit [0.6 ± 1.4 increase in females ( P < .001) vs 0.2 ± 0.6 increase in males ( P = .364)], horizontal saccades [0.6 ± 1.2 increase in females ( P < .001) vs 0.2 ± 0.5 increase in males ( P = .149)], and vertical saccades [0.9 ± 1.9 increase in females ( P < .001) vs 0.3 ± 0.7 increase in males ( P = .206)]. CONCLUSION: Our study did not show sex-based differences in baseline or acute postconcussive symptom reporting in most concussion assessment parameters, challenging previous research suggesting that females report more symptoms than males. Females did have significant differences in symptom provocation using the VOMS.

A Review of Implementation Concepts and Strategies Surrounding Traumatic Brain Injury Clinical Care Guidelines.

Despite considerable efforts to advance the science surrounding traumatic brain injury (TBI), formal efforts supporting the current and future implementation of scientific findings within clinical practice and healthcare policy are limited. While many and varied guidelines inform the clinical management of TBI across the spectrum, clinicians and healthcare systems are not broadly adopting, implementing, and/or adhering to them. As part of the Brain Trauma Blueprint TBI State of the Science, an expert workgroup was assembled to guide this review article, which describes: (1) possible etiologies of inadequate adoption and implementation; (2) enablers to successful implementation strategies; and (3) strategies to mitigate the barriers to adoption and implementation of future research.

External Lumbar Drainage following Traumatic Intracranial Hypertension: A Systematic Review and Meta-Analysis.

BACKGROUND: Traumatic brain injury (TBI) often results in elevations in intracranial pressure (ICP) that are refractory to standard therapies. Several studies have investigated the utility of external lumbar drainage (ELD) in this setting. OBJECTIVE: To evaluate the safety and efficacy of ELD or lumbar puncture with regard to immediate effect on ICP, durability of the effect on ICP, complications, and neurological outcomes in adults with refractory traumatic intracranial hypertension. METHODS: A systematic review and meta-analysis were conducted beginning with a comprehensive search of PubMed/EMBASE. Two investigators reviewed studies for eligibility and extracted data. The strength of evidence was evaluated using GRADE methodology. Random-effects meta-analyses were performed to calculate pooled estimates. RESULTS: Nine articles detailing 6 studies (N = 110) were included. There was moderate evidence that ELD has a significant immediate effect on ICP; the pooled effect size was -19.5 mmHg (95% CI -21.0 to -17.9 mmHg). There was low evidence to indicate a durable effect of ELD on ICP up to at least 24 h following ELD. There was low evidence to indicate that ELD was safe and associated with a low rate of clinical cerebral herniation or meningitis. There was very low evidence pertaining to neurological outcomes. CONCLUSION: Given preliminary data indicating potential safety and feasibility in highly selected cases, the use of ELD in adults with severe TBI and refractory intracranial hypertension in the presence of open basal cisterns and absence of large focal hematoma merits further high-quality investigation; the ideal conditions for potential application remain to be determined.

Phenotyping the Spectrum of Traumatic Brain Injury: A Review and Pathway to Standardization.

It is widely appreciated that the spectrum of traumatic brain injury (TBI), mild through severe, contains distinct clinical presentations, variably referred to as subtypes, phenotypes, and/or clinical profiles. As part of the Brain Trauma Blueprint TBI State of the Science, we review the current literature on TBI phenotyping with an emphasis on unsupervised methodological approaches, and describe five phenotypes that appear similar across reports. However, we also find the literature contains divergent analysis strategies, inclusion criteria, findings, and use of terms. Further, whereas some studies delineate phenotypes within a specific severity of TBI, others derive phenotypes across the full spectrum of severity. Together, these facts confound direct synthesis of the findings. To overcome this, we introduce PhenoBench, a freely available code repository for the standardization and evaluation of raw phenotyping data. With this review and toolset, we provide a pathway toward robust, data-driven phenotypes that can capture the heterogeneity of TBI, enabling reproducible insights and targeted care.

Post-concussion symptom burden in children following motor vehicle collisions.

OBJECTIVE: Motor vehicle collisions generate considerable transmitted forces resulting in traumatic brain injury in children presenting to emergency departments (EDs). To date, no large study has examined post-concussive symptoms in children sustaining concussions in motor vehicle collisions. This study aimed to compare trends in acute post-concussive symptom burden in children with concussion following motor vehicle collisions as compared to other injury mechanisms. METHODS: The study is a secondary analysis of the Predicting Persistent Post-concussive Problems in Pediatrics study, which prospectively recruited a multicenter cohort of 3029 children 5-17 years of age presenting to the ED with concussion from 2013-2015. Post-concussive symptom ratings were obtained at pre-specified time points for 12 weeks post-injury, using the validated Post-Concussion Symptom Inventory (PCSI). Symptom severity and recovery trajectories were measured using delta scores on the PCSI (mean post-injury symptom score minus perceived pre-injury score). A multivariable, longitudinal model evaluated the adjusted effect of mechanism of injury (motor vehicle collisions vs other mechanisms) on mean symptom scores, compared to perceived pre-injury reports, and the temporal change in mean scores over during recovery. RESULTS: Of 3029 study participants, 56 (1.8%) sustained concussion from motor vehicle collisions. Children sustaining concussion in a motor vehicle collision had lower post-concussive symptom scores upon ED presentation, measured as differences from their perceived pre-injury reports, as compared to other injury mechanisms (-0.36 [95% confidence interval (CI) = -0.58, -0.15]). However, the motor vehicle collisions group showed the smallest decline in symptom burden over 1 month following injury (-0.54 [95% CI = -0.81, -0.27]). CONCLUSIONS: Children sustaining concussions in motor vehicle collisions may have lower initial symptom burdens but slower symptom recovery at 1 month compared to other mechanisms of injury and may represent a distinct population for prognostic counseling in the ED requiring further research.

Emergency department implementation of abbreviated magnetic resonance imaging for pediatric traumatic brain injury.

Pediatric head injury is a common presenting complaint in the emergency department (ED), often requiring neuroimaging or ED observation for diagnosis. However, the traditional diagnostic neuroimaging modality, head computed tomography (CT), is associated with radiation exposure while prolonged ED observation impacts patient flow and resource utilization. Recent scientific literature supports abbreviated, or focused and shorter, brain magnetic resonance imaging (MRI) as a feasible and accurate diagnostic alternative to CT for traumatic brain injury. However, this is a relatively new application and its use is not widespread. The aims of this review are to describe the science and applications of abbreviated brain MRI and report a model protocol's development and ED implementation in the evaluation of children with head injury for replication in other institutions.

Sex-Related Differences in Neurosensory Alterations Following Blunt Head Injury.

Background: There is heterogeneity in neurosensory alterations following mild traumatic brain injury. Commonly assessed neurosensory symptoms following head injury include symptom reports and measures of oculomotor impairment, auditory changes, and vestibular impairment. Hypothesis/Purpose: Neurosensory alterations are prevalent acutely following mild traumatic brain injury secondary to blunt head trauma during collegiate varsity sports and may vary by sex and sport. Study Design: Retrospective study of a large collegiate athletic database. Methods: Analyses were performed using an established single University dataset of 177 male and female collegiate varsity athletes who were diagnosed with concussion/mild traumatic brain injury between September 2013 and October 2019. Descriptive and comparative analyses were performed on individual and grouped acute concussion assessments pertaining to neurosensory alterations obtained within 72 h of injury using components of the Sports Concussion Assessment Tool Version 5 and Vestibular/Ocular-Motor Screening. Results: Females had significantly more abnormal smooth pursuit (p-value: 0.045), convergence (p-value: 0.031), and visual motion sensitivity tests results (p-value: 0.023) than males. There were no differences in neurosensory alterations when grouped by overall auditory, vestibular, or oculomotor impairments. The majority of sports-related concussions occurred during football (50, 28.25%), wrestling (21, 11.86%), water polo (15, 8.47%), and basketball (14, 7.91%). Abnormal vestibular assessments were high in these top four sports categories, but statistically significant differences in overall auditory, vestibular, or oculomotor impairments were not reached by individual sport. However, water polo players had higher abnormal individual assessments related to balance reports on the sideline (60.00%, p-value: 0.045) and in the clinic setting (57.14%, p-value: 0.038) as compared to all other sports. Conclusion: While neurosensory alterations are prevalent in both male and female athletes acutely post-concussion, females have a higher incidence of abnormalities in smooth pursuit, convergence, and visual motion sensitivity and may benefit from early rehabilitation.

Smooth Pursuit Eye-Movement Abnormalities Associated With Cervical Spine Whiplash: A Scientific Review and Case Report.

Whiplash injuries may disrupt normal cervical afferent and efferent projections. Oculomotor abnormalities have been reported in chronic whiplash cases, but there is limited knowledge of their presence in acute whiplash and how acute assessment may target early intervention. We present a literature review and case study of a 22-year-old female presenting with an acute concussion and whiplash secondary to a high-speed motor vehicle collision. Smooth pursuit eye-movement abnormalities were observed in relative cervical rotation in the setting of clinical examination of cervicogenic dysfunction. Treatment was focused on cervical manual therapy. While concussive symptoms resolved after seven days, eye-tracking showed a mild improvement and continued to exist in relationship with cervicogenic dysfunction. After completing physical therapy twice weekly for two weeks and in-home exercises, clinical signs and symptoms of whiplash-associated cervicogenic dysfunction and abnormal smooth pursuit eye-movement resolved across all cervical positions. This case highlights the need for ocular-motor impairment assessment following acute whiplash, specifically during cervical rotation. Early intervention should focus on cervical manual therapy and may be important in supporting altered cervical afferents causing oculomotor dysfunctions following acute whiplash.