Caregiver Wellness after Traumatic Brain Injury (CG-Well): Protocol for a randomized clinical trial.

Introduction: After injury, survivors of moderate to severe traumatic brain injury (msTBI) depend on informal family caregivers. Upwards of 77 % of family caregivers experience poor outcomes, such as adverse life changes, poor health-related quality of life, and increased depressive symptoms. Caregivers frequently report minimal support or training to prepare them for their new role. The majority of previously developed caregiver and caregiver/survivor dyad interventions after msTBI focus on providing information to either survivors only, or to long-term caregivers, rather than to the new caregiver. This manuscript describes the protocol of an ongoing randomized control trial, Caregiver Wellness after TBI (CG-Well), developed to provide education, support, and skill-building to caregivers of adults with msTBI, beginning when the survivor is early in the clinical course. Methods: Within two weeks of admission to the ICU, participants are randomized to CG-Well online modules (intervention group, n = 50 dyads) or information, support, and referral (ISR) e-bulletins that exist in the public domain (control group, n = 50 dyads) over the first six months after their family member's msTBI. Both groups receive regular phone calls. The primary outcome is intervention satisfaction at six months. Results: Enrollment began in March 2022 and is projected to complete October 2024. We have enrolled approximately 70 % of participants at this time. Primary analysis completion is anticipated April 2025. Discussion: This RCT is designed to evaluate caregiver satisfaction by addressing the need for tailored supportive care for caregivers of msTBI beginning during the ICU admission. Trial registration: Clinicaltrials. gov Registration Number: NCT05307640.

Post-Intensive Care Syndrome in Neurocritical Care Patients.

Post-intensive care syndrome (PICS) refers to unintended consequences of critical care that manifest as new or worsening impairments in physical functioning, cognitive ability, or mental health. As intensive care unit (ICU) survival continues to improve, PICS is becoming increasingly recognized as a public health problem. Studies that focus on PICS have typically excluded patients with acute brain injuries and chronic neurodegenerative problems. However, patients who require neurocritical care undoubtedly suffer from impairments that overlap substantially with those encompassed by PICS. A major challenge is to distinguish between impairments related to brain injury and those that occur as a consequence of critical care. The general principles for the prevention and management of PICS and multidomain impairments in patients with moderate and severe neurological injuries are similar including the ICU liberation bundle, multidisciplinary team-based care throughout the continuum of care, and increasing awareness regarding the challenges of critical care survivorship among patients, families, and multidisciplinary team members. An extension of this concept, PICS-Family (PICS-F) refers to the mental health consequences of the intensive care experience for families and loved ones of ICU survivors. A dyadic approach to ICU survivorship with an emphasis on recognizing families and caregivers that may be at risk of developing PICS-F after neurocritical care illness can help improve outcomes for ICU survivors. In this review, we will summarize our current understanding of PICS and PICS-F, emerging literature on PICS in severe acute brain injury, strategies for preventing and treating PICS, and share our recommendations for future directions.

Theoretically Based Factors Associated With Stroke Family Caregiver Health.

PURPOSE: Most persons who have had strokes are cared for at home by family members-many of whom experience depressive symptoms and quality of life changes as a result of providing care. The objective of this study is to determine theoretically based factors associated with unhealthy days in stroke family caregivers. RESEARCH DESIGN AND METHODS: Secondary data analysis was conducted using baseline data from a large randomized controlled clinical trial testing the Telephone Assessment and Skill-Building Kit program with 254 family caregivers of persons who have had strokes. Guided by a conceptual model derived from Lazarus' transactional approach to stress, data were analyzed using multiple regression with unhealthy days as the dependent variable and theoretically based factors as independent variables. RESULTS: Caregivers were mostly female (78%), White (71%), spouses (47%), or adult children (29%). Caregivers reported nine unhealthy days on average within the past month. A total of 37.8% of the variance in unhealthy days was explained by caregiver task difficulty, level of optimism, threat appraisal, depressive symptoms, and life changes with depressive symptoms being the strongest individual predictor because of shared variance. CLINICAL RELEVANCE: Unhealthy days is an important part of stroke family caregiver health. Factors associated with unhealthy days in this study provide areas to consider in future intervention development.

Patient-centered mild traumatic brain injury interventions in the emergency department.

INTRODUCTION: Traumatic brain injury (TBI) results in 2.5 million emergency department (ED) visits per year in the US, with mild traumatic brain injury (mTBI) accounting for 90% of cases. There is considerable evidence that many experience chronic symptoms months to years later. This population is rarely represented in interventional studies. Management of adult mTBI in the ED has remained unchanged, without consensus of therapeutic options. The aim of this review was to synthesize existing literature of patient-centered ED treatments for adults who sustain an mTBI, and to identify practices that may offer promise. METHODS: A systematic review was conducted using the PubMed and Cochrane databases, while following PRISMA guidelines. Studies describing pediatric patients, moderate to severe TBI, or interventions outside the ED were excluded. Two reviewers independently performed title and abstract screening. A third blinded reviewer resolved discrepancies. The Mixed Methods Appraisal Tool (MMAT) was employed to assess the methodological quality of the studies. RESULTS: Our search strategy generated 1002 unique titles. 95 articles were selected for full-text screening. The 26 articles chosen for full analysis were grouped into one of the following intervention categories: (1) predictive models for Post-Concussion Syndrome (PCS), (2) discharge instructions, (3) pharmaceutical treatment, (4) clinical protocols, and (5) functional assessment. Studies that implemented a predictive PCS model successfully identified patients at highest risk for PCS. Trials implementing discharge related interventions found the use of video discharge instructions, encouragement of daily light exercise or bed rest, and text messaging did not significantly reduce mTBI symptoms. The use of electronic clinical practice guidelines (eCPG) and longer leaves of absence from work following injury reduced symptoms. Ondansetron was shown to reduce nausea in mTBI patients. Studies implementing ED Observation Units found significant declines in inpatient admissions and length of hospital stay. The use of tablet-based tasks was found to be superior to many standard cognitive assessments. CONCLUSION: Validated instruments are available to aid clinicians in identifying patients at risk for PCS or serious cognitive impairment. EDOU management and evidence-based modifications to discharge instructions may improve mTBI outcomes. Additional research is needed to establish the therapeutic value of medications and lifestyle changes for the treatment of mTBI in the ED.

Acute care bundles should be used for patients with intracerebral haemorrhage: An expert consensus statement.

PURPOSE: Intracerebral haemorrhage (ICH) is the most devastating form of stroke and a major cause of disability. Clinical trials of individual therapies have failed to definitively establish a specific beneficial treatment. However, clinical trials of introducing care bundles, with multiple therapies provided in parallel, appear to clearly reduce morbidity and mortality. Currently, not enough patients receive these interventions in the acute phase. METHODS: We convened an expert group to discuss best practices in ICH and to develop recommendations for bundled care that can be delivered in all settings that treat acute ICH, with a focus on European healthcare systems. FINDINGS: In this consensus paper, we argue for widespread implementation of formalised care bundles in ICH, including specific metrics for time to treatment and criteria for the consideration of neurosurgical therapy. DISCUSSION: There is an extraordinary opportunity to improve clinical care and clinical outcomes in this devastating disease. Substantial evidence already exists for a range of therapies that can and should be implemented now.

Prognostic humility and ethical dilemmas after severe brain injury: Summary, recommendations, and qualitative analysis of Curing Coma Campaign virtual event proceedings.

Background: Patients with severe acute brain injuries (SABI) are at risk of living with long-term disability, frequent medical complications and high rates of mortality. Determining an individual patient's prognosis and conveying this to family members/caregivers can be challenging. We conducted a webinar with experts in neurosurgery, neurocritical care, neuro-palliative care, neuro-ethics, and rehabilitation as part of the Curing Coma Campaign, which is supported by the Neurocritical Care Society. The webinar discussed topics focused on prognostic uncertainty, communicating prognosis to family members/caregivers, gaps within healthcare systems, and research infrastructure as it relates to patients experiencing SABI. The purpose of this manuscript is to describe the themes that emerged from this virtual discussion. Methods: A qualitative analysis of a webinar "Prognostic Humility and Ethical Dilemmas in Acute Brain Injury" was organized as part of the Neurocritical Care Society's Curing Coma Campaign. A multidisciplinary group of experts was invited as speakers and moderators of the webinar. The content of the webinar was transcribed verbatim. Two qualitative researchers (NK and BM) read and re-read the transcription, and familiarized themselves with the text. The two coders developed and agreed on a code book, independently coded the transcript, and discussed any discrepancies. The transcript was analyzed using inductive thematic analysis of codes and themes that emerged within the expert discussion. Results: We coded 168 qualitative excerpts within the transcript. Two main themes were discussed: (1) the concept of prognostic uncertainty in the acute setting, and (2) lack of access to and evidence for quality rehabilitation and specialized continuum of care efforts specific to coma research. Within these two main themes, we found 5 sub-themes, which were broken down into 23 unique codes. The most frequently described code was the need for clinicians to acknowledge our own uncertainties when we discuss prognosis with families, which was mentioned 13 times during the webinar. Several strategies were described for speaking with surrogates of patients who have had a severe brain injury resulting in SABI. We also identified important gaps in the United States health system and in research to improve the care of patients with severe brain injuries. Conclusion: As a result of this webinar and expert discussion, authors identified and analyzed themes related to prognostic uncertainty with SABI. Recommendations were outlined for clinicians who engage with surrogates of patients with SABI to foster informed decisions for their loved one. Finally, recommendations for changes in healthcare systems and research support are provided in order to continue to propel SABI science forward to improve future prognostic certainty.

Iterative Development of the Caregiver Wellness After Traumatic Brain Injury Program (CG-Well).

OBJECTIVES: (1) To iteratively design a web/phone-based intervention to support caregivers of adults acutely following traumatic brain injury (TBI), Caregiver Wellness (CG-Well), and (2) to obtain qualitative and quantitative feedback on CG-Well from experts and caregivers to refine the intervention. SETTING: A level I trauma and tertiary medical center. PARTICIPANTS: Convenience sample of a total of 19 caregivers and 25 experts. DESIGN: Multistep prospective study with iterative changes to CG-Well: (1) developed intervention content based on qualitative feedback from a prior study and literature review; (2) obtained qualitative feedback from 10 experts; (3) refined content using a modified Delphi approach involving 4 caregivers and 6 experts followed by qualitative interviews with 9 caregivers; (4) designed CG-Well website and videos; and (5) obtained feedback on program acceptability, appropriateness, and feasibility from 6 caregivers and 9 experts. INTERVENTIONS: CG-Well included content on TBI, self-care and support, and skill-building strategies delivered through a website and telephone calls. MAIN OUTCOME MEASURES: Qualitative data were analyzed using content analysis. Caregivers and experts completed Likert-type scales to rate module relevance, clarity, accuracy, utility and website acceptability, appropriateness, and feasibility (1 = strongly disagree to 5 = strongly agree). Means and standard deviations (SD) characterized ratings. RESULTS: Qualitative findings were instrumental in designing and refining CG-Well. Ratings were positive for modules (means and SD for relevant [4.9, 0.33], clear [4.6, 0.53], accurate [4.9, 0.33], and useful [5, 0]) and the website (means and SD for acceptable [4.8, 0.36], appropriate [4.8, 0.35], and feasible [4.8, 0.36]). CONCLUSIONS: The iterative design process for CG-Well resulted in a highly acceptable program. An early-stage randomized controlled trial is underway to estimate treatment effects for a future well-powered clinical trial.

Emergency department management of infective endocarditis-associated stroke.

Stroke in patients with endocarditis is a unique, highly morbid condition requiring a high index of suspicion for diagnosis. This issue reviews the historical and physical examination factors that can provide clues to the etiology. The workup of these patients, involving both infection-focused and stroke-focused laboratory testing and neuroimaging, is discussed. The mainstay of treatment is empiric antibiotics, as thrombolytics are contraindicated. Recent evidence regarding the use of mechanical thrombectomy in largevessel occlusion strokes is discussed, as well as surgical options and consultation strategies with stroke, neurocritical care, infectious disease, and neurosurgery teams.

Outcomes in Patients With Mild Traumatic Brain Injury Without Acute Intracranial Traumatic Injury.

Importance: Traumatic brain injury (TBI) affects millions of people in the US each year. Most patients with TBI seen in emergency departments (EDs) have a Glasgow Coma Scale (GCS) score of 15 and a head computed tomography (CT) scan showing no acute intracranial traumatic injury (negative head CT scan), yet the short-term and long-term functional outcomes of this subset of patients remain unclear. Objective: To describe the 2-week and 6-month recovery outcomes in a cohort of patients with mild TBI with a GCS score of 15 and a negative head CT scan. Design, Setting, and Participants: This cohort study analyzed participants who were enrolled from January 1, 2014, to December 31, 2018, in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study, a prospective, observational cohort study of patients with TBI that was conducted in EDs of 18 level I trauma centers in urban areas. Of the total 2697 participants in the TRACK-TBI study, 991 had a GCS score of 15 and negative head CT scan and were eligible for inclusion in this analysis. Data were analyzed from September 1, 2021, to May 30, 2022. Main Outcomes and Measures: The primary outcome was the Glasgow Outcome Scale-Extended (GOS-E) score, which was stratified according to functional recovery (GOS-E score, 8) vs incomplete recovery (GOS-E score, <8), at 2 weeks and 6 months after the injury. The secondary outcome was severity of mild TBI-related symptoms assessed by the Rivermead Post Concussion Symptoms Questionnaire (RPQ) total score. Results: A total of 991 participants (mean [SD] age, 38.5 [15.8] years; 631 male individuals [64%]) were included. Of these participants, 751 (76%) were followed up at 2 weeks after the injury: 204 (27%) had a GOS-E score of 8 (functional recovery), and 547 (73%) had a GOS-E scores less than 8 (incomplete recovery). Of 659 participants (66%) followed up at 6 months after the injury, 287 (44%) had functional recovery and 372 (56%) had incomplete recovery. Most participants with incomplete recovery reported that they had not returned to baseline or preinjury life (88% [479 of 546]; 95% CI, 85%-90%). Mean RPQ score was 16 (95% CI, 14-18; P < .001) points lower at 2 weeks (7 vs 23) and 18 (95% CI, 16-20; P < .001) points lower at 6 months (4 vs 22) in participants with a GOS-E score of 8 compared with those with a GOS-E score less than 8. Conclusions and Relevance: This study found that most participants with a GCS score of 15 and negative head CT scan reported incomplete recovery at 2 weeks and 6 months after their injury. The findings suggest that emergency department clinicians should recommend 2-week follow-up visits for these patients to identify those with incomplete recovery and to facilitate their rehabilitation.

An independent, external validation and component analysis of the Surviving Penetrating Injury to the Brain score for civilian cranial gunshot injuries.

OBJECTIVE: The Surviving Penetrating Injury to the Brain (SPIN) score utilizes clinical variables to estimate in-hospital and 6-month mortality for patients with civilian cranial gunshot wounds (cGSWs) and demonstrated good discrimination (area under the receiver operating characteristic curve [AUC] 0.880) in an initial validation study. The goal of this study was to provide an external, independent validation of the SPIN score for in-hospital and 6-month mortality. METHODS: To accomplish this, the authors retrospectively reviewed 6 years of data from their institutional trauma registry. Variables used to determine SPIN score were collected, including sex, transfer status, injury motive, pupillary reactivity, motor component of the Glasgow Coma Scale (mGCS), Injury Severity Score (ISS), and international normalized ratio (INR) at admission. Multivariable logistic regression analysis identified variables associated with mortality. The authors compared AUC between models by using a nonparametric test for equality. RESULTS: Of the 108 patients who met the inclusion criteria, 101 had all SPIN score components available. The SPIN model had an AUC of 0.962. The AUC for continuous mGCS score alone (0.932) did not differ significantly from the AUC for the full SPIN model (p = 0.26). The AUC for continuous mGCS score (0.932) was significantly higher compared to categorical mGCS score (0.891, p = 0.005). Use of only mGCS score resulted in fewer exclusions due to missing data. No additional variable included in the predictive model alongside continuous mGCS score was a significant predictor of inpatient mortality, 6-month mortality, or increased model discrimination. CONCLUSIONS: Given these findings, continuous 6-point mGCS score may be sufficient as a generalizable predictor of inpatient and 6-month mortality in patients with cGSW, demonstrating excellent discrimination and reduced bias due to missing data.

Theoretically Based Factors Affecting Stroke Family Caregiver Health: An Integrative Review.

Stroke family caregivers often neglect their own health while providing care. Rigorous reviews have focused on stroke caregiver needs and outcomes; however, a comprehensive review of stroke caregiver health is lacking. The purpose of this integrative review was to determine factors associated with stroke family caregiver health. Using a PRISMA flow diagram and Rayyan software, 41 studies were identified published from January 2000 to December 2020. Databases included Cochrane Reviews, Cochrane Trials, PsycINFO, Ovid MEDLINE, PubMed, EBSCOhost MEDLINE, Embase, and CINAHL. Rigorous guidelines were used to critique the 41 articles. Health measures were global in nature, lacking details regarding health promotion activities important to stroke family caregiver health. Common factors associated with caregiver health were depressive symptoms and burden. Further research is needed to design more situation-specific instruments to measure stroke family caregiver health, as well as interventions to reduce depressive symptoms and burden while promoting caregiver health.

Comparing the Quality of Life after Brain Injury-Overall Scale and Satisfaction with Life Scale as Outcome Measures for Traumatic Brain Injury Research.

It is important to measure quality of life (QoL) after traumatic brain injury (TBI), yet limited studies have compared QoL inventories. In 2579 TBI patients, orthopedic trauma controls, and healthy friend control participants, we compared the Quality of Life After Brain Injury-Overall Scale (QOLIBRI-OS), developed for TBI patients, to the Satisfaction with Life Scale (SWLS), an index of generic life satisfaction. We tested the hypothesis that group differences (TBI and orthopedic trauma vs. healthy friend controls) would be larger for the QOLIBRI-OS than the SWLS and that the QOLIBRI-OS would manifest more substantial changes over time in the injured groups, demonstrating more relevance of the QOLIBRI-OS to traumatic injury recovery. (1) We compared the group differences (TBI vs. orthopedic trauma control vs. friend control) in QoL as indexed by the SWLS versus the QOLIBRI-OS and (2) characterized changes across time in these two inventories across 1 year in these three groups. Our secondary objective was to characterize the relationship between TBI severity and QoL. As compared with healthy friend controls, the QOLIBRI reflected greater reductions in QoL than the SWLS for both the TBI group (all time points) and the orthopedic trauma control group (2 weeks and 3 months). The QOLIBRI-OS better captured expected improvements in QoL during the injury recovery course in injured groups than the SWLS, which demonstrated smaller changes over time. TBI severity was not consistently or robustly associated with self-reported QoL. The findings imply that, as compared with the SWLS, the QOLIBRI-OS appears to identify QoL issues more specifically relevant to traumatically injured patients and may be a more appropriate primary QoL outcome measure for research focused on the sequelae of traumatic injuries.

Functional Outcomes Over the First Year After Moderate to Severe Traumatic Brain Injury in the Prospective, Longitudinal TRACK-TBI Study.

Importance: Moderate to severe traumatic brain injury (msTBI) is a major cause of death and disability in the US and worldwide. Few studies have enabled prospective, longitudinal outcome data collection from the acute to chronic phases of recovery after msTBI. Objective: To prospectively assess outcomes in major areas of life function at 2 weeks and 3, 6, and 12 months after msTBI. Design, Setting, and Participants: This cohort study, as part of the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study, was conducted at 18 level 1 trauma centers in the US from February 2014 to August 2018 and prospectively assessed longitudinal outcomes, with follow-up to 12 months postinjury. Participants were patients with msTBI (Glasgow Coma Scale scores 3-12) extracted from a larger group of patients with mild, moderate, or severe TBI who were enrolled in TRACK-TBI. Data analysis took place from October 2019 to April 2021. Exposures: Moderate or severe TBI. Main Outcomes and Measures: The Glasgow Outcome Scale-Extended (GOSE) and Disability Rating Scale (DRS) were used to assess global functional status 2 weeks and 3, 6, and 12 months postinjury. Scores on the GOSE were dichotomized to determine favorable (scores 4-8) vs unfavorable (scores 1-3) outcomes. Neurocognitive testing and patient reported outcomes at 12 months postinjury were analyzed. Results: A total of 484 eligible patients were included from the 2679 individuals in the TRACK-TBI study. Participants with severe TBI (n = 362; 283 men [78.2%]; median [interquartile range] age, 35.5 [25-53] years) and moderate TBI (n = 122; 98 men [80.3%]; median [interquartile range] age, 38 [25-53] years) were comparable on demographic and premorbid variables. At 2 weeks postinjury, 36 of 290 participants with severe TBI (12.4%) and 38 of 93 participants with moderate TBI (41%) had favorable outcomes (GOSE scores 4-8); 301 of 322 in the severe TBI group (93.5%) and 81 of 103 in the moderate TBI group (78.6%) had moderate disability or worse on the DRS (total score ≥4). By 12 months postinjury, 142 of 271 with severe TBI (52.4%) and 54 of 72 with moderate TBI (75%) achieved favorable outcomes. Nearly 1 in 5 participants with severe TBI (52 of 270 [19.3%]) and 1 in 3 with moderate TBI (23 of 71 [32%]) reported no disability (DRS score 0) at 12 months. Among participants in a vegetative state at 2 weeks, 62 of 79 (78%) regained consciousness and 14 of 56 with available data (25%) regained orientation by 12 months. Conclusions and Relevance: In this study, patients with msTBI frequently demonstrated major functional gains, including recovery of independence, between 2 weeks and 12 months postinjury. Severe impairment in the short term did not portend poor outcomes in a substantial minority of patients with msTBI. When discussing prognosis during the first 2 weeks after injury, clinicians should be particularly cautious about making early, definitive prognostic statements suggesting poor outcomes and withdrawal of life-sustaining treatment in patients with msTBI.

Pathological Computed Tomography Features Associated With Adverse Outcomes After Mild Traumatic Brain Injury: A TRACK-TBI Study With External Validation in CENTER-TBI.

Importance: A head computed tomography (CT) with positive results for acute intracranial hemorrhage is the gold-standard diagnostic biomarker for acute traumatic brain injury (TBI). In moderate to severe TBI (Glasgow Coma Scale [GCS] scores 3-12), some CT features have been shown to be associated with outcomes. In mild TBI (mTBI; GCS scores 13-15), distribution and co-occurrence of pathological CT features and their prognostic importance are not well understood. Objective: To identify pathological CT features associated with adverse outcomes after mTBI. Design, Setting, and Participants: The longitudinal, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study enrolled patients with TBI, including those 17 years and older with GCS scores of 13 to 15 who presented to emergency departments at 18 US level 1 trauma centers between February 26, 2014, and August 8, 2018, and underwent head CT imaging within 24 hours of TBI. Evaluations of CT imaging used TBI Common Data Elements. Glasgow Outcome Scale-Extended (GOSE) scores were assessed at 2 weeks and 3, 6, and 12 months postinjury. External validation of results was performed via the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Data analyses were completed from February 2020 to February 2021. Exposures: Acute nonpenetrating head trauma. Main Outcomes and Measures: Frequency, co-occurrence, and clustering of CT features; incomplete recovery (GOSE scores <8 vs 8); and an unfavorable outcome (GOSE scores <5 vs ≥5) at 2 weeks and 3, 6, and 12 months. Results: In 1935 patients with mTBI (mean [SD] age, 41.5 [17.6] years; 1286 men [66.5%]) in the TRACK-TBI cohort and 2594 patients with mTBI (mean [SD] age, 51.8 [20.3] years; 1658 men [63.9%]) in an external validation cohort, hierarchical cluster analysis identified 3 major clusters of CT features: contusion, subarachnoid hemorrhage, and/or subdural hematoma; intraventricular and/or petechial hemorrhage; and epidural hematoma. Contusion, subarachnoid hemorrhage, and/or subdural hematoma features were associated with incomplete recovery (odds ratios [ORs] for GOSE scores <8 at 1 year: TRACK-TBI, 1.80 [95% CI, 1.39-2.33]; CENTER-TBI, 2.73 [95% CI, 2.18-3.41]) and greater degrees of unfavorable outcomes (ORs for GOSE scores <5 at 1 year: TRACK-TBI, 3.23 [95% CI, 1.59-6.58]; CENTER-TBI, 1.68 [95% CI, 1.13-2.49]) out to 12 months after injury, but epidural hematoma was not. Intraventricular and/or petechial hemorrhage was associated with greater degrees of unfavorable outcomes up to 12 months after injury (eg, OR for GOSE scores <5 at 1 year in TRACK-TBI: 3.47 [95% CI, 1.66-7.26]). Some CT features were more strongly associated with outcomes than previously validated variables (eg, ORs for GOSE scores <5 at 1 year in TRACK-TBI: neuropsychiatric history, 1.43 [95% CI .98-2.10] vs contusion, subarachnoid hemorrhage, and/or subdural hematoma, 3.23 [95% CI 1.59-6.58]). Findings were externally validated in 2594 patients with mTBI enrolled in the CENTER-TBI study. Conclusions and Relevance: In this study, pathological CT features carried different prognostic implications after mTBI to 1 year postinjury. Some patterns of injury were associated with worse outcomes than others. These results support that patients with mTBI and these CT features need TBI-specific education and systematic follow-up.

Diffusion-Weighted Imaging Reveals Distinct Patterns of Cytotoxic Edema in Patients with Subdural Hematomas.

Subdural hematomas (SDHs) are increasingly common and can cause ischemic brain injury. Previous work has suggested that this is driven largely by vascular compression from herniation, although this work was done before the era of magnetic resonance imaging (MRI). We thus sought to study SDH-related ischemic brain injury by looking at patterns of cytotoxic edema on diffusion-weighted MRI. To do so, we identified all SDH patients at a single institution from 2015 to 2019 who received an MRI within 2 weeks of presentation. We reviewed all MRIs for evidence of restricted diffusion consistent with cytotoxic edema. Cases were excluded if the restricted diffusion could have occurred as a result of alternative etiologies (e.g., cardioembolic stroke or diffuse axonal injury). We identified 450 SDH patients who received an MRI within 2 weeks of presentation. Twenty-nine patients (∼6.5% of all MRIs) had SDH-related cytotoxic edema, which occurred in two distinct patterns. In one pattern (N = 9), patients presented as comatose with severe midline shift and were found to have cytotoxic edema in the vascular territories of the anterior and posterior cerebral artery, consistent with herniation-related vascular compression. In the other pattern (N = 19), patients often presented as awake with less midline shift and developed cytotoxic edema in the cortex adjacent to the SDH outside of typical vascular territories (peri-SDH cytotoxic edema). Both patterns occurred in 1 patient. The peri-SDH cytotoxic edema pattern is a newly described type of secondary injury and may involve direct toxic effects of the SDH, spreading depolarizations, or other mechanisms.

Association of Sex and Age With Mild Traumatic Brain Injury-Related Symptoms: A TRACK-TBI Study.

Importance: Knowledge of differences in mild traumatic brain injury (mTBI) recovery by sex and age may inform individualized treatment of these patients. Objective: To identify sex-related differences in symptom recovery from mTBI; secondarily, to explore age differences within women, who demonstrate poorer outcomes after TBI. Design, Setting, and Participants: The prospective cohort study Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) recruited 2000 patients with mTBI from February 26, 2014, to July 3, 2018, and 299 patients with orthopedic trauma (who served as controls) from January 26, 2016, to July 27, 2018. Patients were recruited from 18 level I trauma centers and followed up for 12 months. Data were analyzed from August 19, 2020, to March 3, 2021. Exposures: Patients with mTBI (defined by a Glasgow Coma Scale score of 13-15) triaged to head computed tomography in 24 hours or less; patients with orthopedic trauma served as controls. Main Outcomes and Measures: Measured outcomes included (1) the Rivermead Post Concussion Symptoms Questionnaire (RPQ), a 16-item self-report scale that assesses postconcussion symptom severity over the past 7 days relative to preinjury; (2) the Posttraumatic Stress Disorder Checklist for the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (PCL-5), a 20-item test that measures the severity of posttraumatic stress disorder symptoms; (3) the Patient Health Questionnaire-9 (PHQ-9), a 9-item scale that measures depression based on symptom frequency over the past 2 weeks; and (4) the Brief Symptom Inventory-18 (BSI-18), an 18-item scale of psychological distress (split into Depression and Anxiety subscales). Results: A total of 2000 patients with mTBI (1331 men [67%; mean (SD) age, 41.0 (17.3) years; 1026 White (78%)] and 669 women [33%; mean (SD) age, 43.0 (18.5) years; 505 (76%) White]). After adjustment of multiple comparisons, significant TBI × sex interactions were observed for cognitive symptoms (B = 0.76; 5% false discovery rate-corrected P = .02) and somatic RPQ symptoms (B = 0.80; 5% false discovery rate-corrected P = .02), with worse symptoms in women with mTBI than men, but no sex difference in symptoms in control patients with orthopedic trauma. Within the female patients evaluated, there was a significant TBI × age interaction for somatic RPQ symptoms, which were worse in female patients with mTBI aged 35 to 49 years compared with those aged 17 to 34 years (B = 1.65; P = .02) or older than 50 years (B = 1.66; P = .02). Conclusions and Relevance: This study found that women were more vulnerable than men to persistent mTBI-related cognitive and somatic symptoms, whereas no sex difference in symptom burden was seen after orthopedic injury. Postconcussion symptoms were also worse in women aged 35 to 49 years than in younger and older women, but further investigation is needed to corroborate these findings and to identify the mechanisms involved. Results suggest that individualized clinical management of mTBI should consider sex and age, as some women are especially predisposed to chronic postconcussion symptoms even 12 months after injury.

Latent Profile Analysis of Neuropsychiatric Symptoms and Cognitive Function of Adults 2 Weeks After Traumatic Brain Injury: Findings From the TRACK-TBI Study.

Importance: Heterogeneity across patients with traumatic brain injury (TBI) presents challenges for clinical care and intervention design. Identifying distinct clinical phenotypes of TBI soon after injury may inform patient selection for precision medicine clinical trials. Objective: To investigate whether distinct neurobehavioral phenotypes can be identified 2 weeks after TBI and to characterize the degree to which early neurobehavioral phenotypes are associated with 6-month outcomes. Design, Setting, and Participants: This prospective cohort study included patients presenting to 18 US level 1 trauma centers within 24 hours of TBI from 2014 to 2019 as part of the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study. Data were analyzed from January 28, 2020, to January 11, 2021. Exposures: TBI. Main Outcomes and Measures: Latent profiles (LPs) were derived from common dimensions of neurobehavioral functioning at 2 weeks after injury, assessed through National Institutes of Health TBI Common Data Elements (ie, Brief Symptom Inventory-18, Patient Health Questionnaire-9 Depression checklist, Posttraumatic Stress Disorder Checklist for DSM-5, PROMIS Pain Intensity scale, Insomnia Severity Index, Rey Auditory Verbal Learning Test, Wechsler Adult Intelligence Scale-Fourth Edition Coding and Symbol Search subtests, Trail Making Test, and NIH Toolbox Cognitive Battery Pattern Comparison Processing Speed, Dimensional Change Card Sort, Flanker Inhibitory Control and Attention, and Picture Sequence Memory subtests). Six-month outcomes were the Satisfaction With Life Scale (SWLS), Quality of Life after Brain Injury-Overall Scale (QOLIBRI-OS), Glasgow Outcome Scale-Extended (GOSE), and Rivermead Post-Concussion Symptoms Questionnaire (RPQ). Results: Among 1757 patients with TBI included, 1184 (67.4%) were men, and the mean (SD) age was 39.9 (17.0) years. LP analysis revealed 4 distinct neurobehavioral phenotypes at 2 weeks after injury: emotionally resilient (419 individuals [23.8%]), cognitively impaired (368 individuals [20.9%]), cognitively resilient (620 individuals [35.3%]), and neuropsychiatrically distressed (with cognitive weaknesses; 350 individuals [19.9%]). Adding LP group to models including demographic characteristics, medical history, Glasgow Coma Scale score, and other injury characteristics was associated with significantly improved estimation of association with 6-month outcome (GOSE R2 increase = 0.09-0.19; SWLS R2 increase = 0.12-0.22; QOLIBRI-OS R2 increase = 0.14-0.32; RPQ R2 = 0.13-0.34). Conclusions and Relevance: In this cohort study of patients with TBI presenting to US level-1 trauma centers, qualitatively distinct profiles of symptoms and cognitive functioning were identified at 2 weeks after TBI. These distinct phenotypes may help optimize clinical decision-making regarding prognosis, as well as selection and stratification for randomized clinical trials.