Traumatic Brain Injury Subgroups Research Articles

P.115 The national impact of traumatic brain injury on labor markets: a canada-wide observational cohort study of post-injury employment and personal income loss

Background: Employment and personal income loss after traumatic brain injury (TBI) is a major source of post-injury stress and barrier to societal reintegration for affected patients. We sought to quantify the labor market implications for tax-filing adult TBI survivors. Methods: We performed a matched difference-in-difference analysis using a national retrospective cohort of working adult TBI survivors injured between 2007-2017. Linear and logistic mixed effects regressions were used to estimate the magnitude of personal income loss and proportion of patients displaced from the workforce in the three post-injury years (Y+1 to Y+3). Results: Among 18,050 patients identified with TBI, the adjusted average loss of personal annual income was $-7,635 dollars in Y+1 and $-5,000 in Y+3. An additional -7.8% individuals were newly unemployed compared to the pre-injury baseline. For mild, moderate, and severe TBI subgroups, income loss was $-3354, $-6750, and $-17375 respectively in Y+3; the proportion of newly unemployed individuals in Y+3 was 5.8%, 9.2%, and 20% lower than baseline. We estimated 500 million dollars of incurred labor markets losses related to TBI in Canada. Conclusions: This work represents the first national cohort data quantifying the labor market implications of TBI. These results may be used to inform post-injury care pathways and vocational rehabilitation.

Mental Illness in the 2 Years Prior to Pregnancy in a Population With Traumatic Brain Injury: A Cross-Sectional Study: La maladie mentale dans les deux ans précédant une grossesse dans une population souffrant de lésion cérébrale traumatique : une étude transversale.

Existing studies, in mostly male samples such as veterans and athletes, show a strong association between traumatic brain injury (TBI) and mental illness. Yet, while an understanding of mental health before pregnancy is critical for informing preconception and perinatal supports, there are no data on the prevalence of active mental illness before pregnancy in females with TBI. We examined the prevalence of active mental illness ≤2 years before pregnancy (1) in a population with TBI, and (2) in subgroups defined by sociodemographic, health, and injury-related characteristics, all compared to those without TBI. This population-based cross-sectional study was completed in Ontario, Canada, from 2012 to 2020. Modified Poisson regression generated adjusted prevalence ratios (aPRs) of active mental illness ≤2 years before pregnancy in 15,585 females with TBI versus 846,686 without TBI. We then used latent class analysis to identify subgroups with TBI according to sociodemographic, health, and injury-related characteristics and subsequently compared them to females without TBI on their outcome prevalence. Females with TBI had a higher prevalence of active mental illness ≤2 years before pregnancy than those without TBI (44.1% vs. 25.9%; aPR 1.46, 95% confidence interval, 1.43 to 1.49). There were 3 TBI subgroups, with Class 1 (low-income, past assault, recent TBI described as intentional and due to being struck by/against) having the highest outcome prevalence. Females with TBI, and especially those with a recent intentional TBI, have a high prevalence of mental illness before pregnancy. They may benefit from mental health screening and support in the post-injury, preconception, and perinatal periods. Mental illness in the 2 years before pregnancy in a population with traumatic brain injury. Research has shown a strong association between traumatic brain injury (TBI) and mental illness. Most previous studies have been conducted in primarily male samples, like veterans and professional athletes. Understanding mental health before pregnancy is important for deciding what supports people need before and during pregnancy. However, there are no studies on the frequency of mental illness in females with TBI before a pregnancy. We examined the frequency of mental illness 2 years before pregnancy in a population with TBI, and in subgroups defined by different social, health, and injury-related characteristics, compared to those without TBI. We undertook a population-wide study of all females with and without TBI in Ontario, Canada, with a birth in 2012-2020. We used statistical models to compare these groups on the presence of mental illness in the 2 years before pregnancy, before and after accounting for social and health characteristics. We also identified subgroups with TBI according to their social (e.g., poverty), health (e.g., chronic conditions), and injury-related characteristics (e.g., cause of injury) and subsequently compared them to females without TBI on their frequency of mental illness in the 2 years before pregnancy. Forty-four percent of females with TBI had mental illness in the 2 years before pregnancy compared to 25% of those without TBI. There were 3 TBI subgroups. Females with low-income, past assault, and injuries that were described as being intentional had the highest frequency of mental illness in the 2 years before pregnancy. Females with TBI may benefit from mental health screening and support post-injury and around the time of pregnancy.

"Should We Phenobarb-it-All?" A Phenobarbital-Based Protocol for Non-Intensive Care Unit Trauma Patients at High Risk of or Experiencing Alcohol Withdrawal.

Alcohol use is frequent in trauma patients and alcohol withdrawal syndrome (AWS) is associated with significant morbidity. Benzodiazepines are commonly used for AWS, but may cause neurologic and respiratory adverse events (AEs). The objective was to evaluate the effectiveness and safety of a phenobarbital-based protocol for the treatment of AWS in non-intensive care unit (ICU) trauma patients. Adult non-ICU trauma patients at high risk of or experiencing AWS PRE and POST implementation of a phenobarbital-based protocol were included. Outcomes were AWS-related complications (AWS-RC), benzodiazepine use, adjunctive medication use, hospital length of stay (HLOS), and medication-related AEs. Subgroup analyses were performed on patients with traumatic brain injury (TBI), rib fractures, and at high risk of severe AWS. Overall, 110 patients were included (51 PRE, 59 POST). AWS-RC developed in 17 PRE patients compared to 10 POST patients (33% vs 17%; P = .05). PRE patients were more likely to receive benzodiazepines (88% vs 42%, P < .0001) and higher total dose (11 vs 4mg lorazepam equivalent; P = .001). No difference noted in HLOS (8 vs 8 days, P = .27), adjunctive medication use (49% vs 54%, P = .60), or AEs (57% vs 39%, P = .06). There was no difference in AWS-RC in the TBI subgroup (P = .19), less AEs in the rib fracture POST subgroup (P = .04), and less AWS-RC in the high risk of severe AWS POST subgroup (P = .03). A phenobarbital-based protocol in trauma patients is effective in preventing AWS-RC and decreasing benzodiazepine use without increasing AEs.

Balanced Crystalloid Solution or Normal Saline in Fluid Resuscitation in Critically Ill Patients: A Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Trials

Background: Both balanced crystalloid solution and normal saline are commonly used for fluid therapy in critically ill patients. However, the association between the types of crystalloid solution and patient outcomes remains inconclusive. Materials and Methods: The authors performed a search using Pubmed, Embase, and Cochrane Central Register through January 2022. Randomized controlled trials (RCTs) comparing balanced crystalloids and normal saline in non-perioperative fluid resuscitation for critically ill adult patients were included. The primary outcome was 30-day mortality. A trial sequential analysis (TSA) was performed to assess the effect of each type of fluid on the outcomes. Secondary outcomes included the incidence of acute kidney injury (AKI), renal replacement therapy (RRT), and other pre-specified outcomes. Results: Ten RCTs were identified and included 36,233 participants. Between the balanced crystalloids and the normal saline group, there were no significant differences in mortality at 30 days (relative risk [RR] 0.95, 95% confidence interval [CI] 0.89 to 1.02, I²=0), the incidence of AKI (RR 0.95, 95% CI 0.90 to 1.01, I²=0), and RRT (RR 0.93, 95% CI 0.86 to 1.01, I²=13). However, patients receiving balanced crystalloids demonstrated a significantly lower serum chloride level than the patients receiving normal saline (MD –1.95, 95% CI –3.45 to –0.45, I²=99). There was also no mortality difference in the sepsis and traumatic brain injury subgroups. The TSA confirmed the absence of an effect on mortality at 30 days and the incidence of AKI. Conclusion: In critically ill patients, the use of balanced crystalloids does not decrease 30-day mortality or the incidence of AKI and RRT. However, data in specific subgroups of patients were underpowered and further studies are required. There were signals of benefit and risk of the balanced salt solution in the subgroups of sepsis and traumatic brain injury. Trial registration: The present study was registered in the PROSPERO database, CRD42021275796. Keywords: Balanced crystalloid; Normal saline; Critically ill patients; Mortality; Acute kidney injury

Performance of the IMPACT and CRASH prognostic models for traumatic brain injury in a contemporary multicenter cohort: a TRACK-TBI study.

The International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) and Corticosteroid Randomization After Significant Head Injury (CRASH) prognostic models for mortality and outcome after traumatic brain injury (TBI) were developed using data from 1984 to 2004. This study examined IMPACT and CRASH model performances in a contemporary cohort of US patients. The prospective 18-center Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study (enrollment years 2014-2018) enrolled subjects aged ≥ 17 years who presented to level I trauma centers and received head CT within 24 hours of TBI. Data were extracted from the subjects who met the model criteria (for IMPACT, Glasgow Coma Scale [GCS] score 3-12 with 6-month Glasgow Outcome Scale-Extended [GOSE] data [n = 441]; for CRASH, GCS score 3-14 with 2-week mortality data and 6-month GOSE data [n = 831]). Analyses were conducted in the overall cohort and stratified on the basis of TBI severity (severe/moderate/mild TBI defined as GCS score 3-8/9-12/13-14), age (17-64 years or ≥ 65 years), and the 5 top enrolling sites. Unfavorable outcome was defined as GOSE score 1-4. Original IMPACT and CRASH model coefficients were applied, and model performances were assessed by calibration (intercept [< 0 indicated overprediction; > 0 indicated underprediction] and slope) and discrimination (c-statistic). Overall, the IMPACT models overpredicted mortality (intercept -0.79 [95% CI -1.05 to -0.53], slope 1.37 [1.05-1.69]) and acceptably predicted unfavorable outcome (intercept 0.07 [-0.14 to 0.29], slope 1.19 [0.96-1.42]), with good discrimination (c-statistics 0.84 and 0.83, respectively). The CRASH models overpredicted mortality (intercept -1.06 [-1.36 to -0.75], slope 0.96 [0.79-1.14]) and unfavorable outcome (intercept -0.60 [-0.78 to -0.41], slope 1.20 [1.03-1.37]), with good discrimination (c-statistics 0.92 and 0.88, respectively). IMPACT overpredicted mortality and acceptably predicted unfavorable outcome in the severe and moderate TBI subgroups, with good discrimination (c-statistic ≥ 0.81). CRASH overpredicted mortality in the severe and moderate TBI subgroups and acceptably predicted mortality in the mild TBI subgroup, with good discrimination (c-statistic ≥ 0.86); unfavorable outcome was overpredicted in the severe and mild TBI subgroups with adequate discrimination (c-statistic ≥ 0.78), whereas calibration was nonlinear in the moderate TBI subgroup. In subjects ≥ 65 years of age, the models performed variably (IMPACT-mortality, intercept 0.28, slope 0.68, and c-statistic 0.68; CRASH-unfavorable outcome, intercept -0.97, slope 1.32, and c-statistic 0.88; nonlinear calibration for IMPACT-unfavorable outcome and CRASH-mortality). Model performance differences were observed across the top enrolling sites for mortality and unfavorable outcome. The IMPACT and CRASH models adequately discriminated mortality and unfavorable outcome. Observed overestimations of mortality and unfavorable outcome underscore the need to update prognostic models to incorporate contemporary changes in TBI management and case-mix. Investigations to elucidate the relationships between increased survival, outcome, treatment intensity, and site-specific practices will be relevant to improve models in specific TBI subpopulations (e.g., older adults), which may benefit from the inclusion of blood-based biomarkers, neuroimaging features, and treatment data.

Profiles of Cognitive Functioning at 6 Months After Traumatic Brain Injury Among Patients in Level I Trauma Centers

Cognitive dysfunction is common after traumatic brain injury (TBI), with a well-established dose-response relationship between TBI severity and likelihood or magnitude of persistent cognitive impairment. However, patterns of cognitive dysfunction in the long-term (eg, 6-month) recovery period are less well known. To characterize the prevalence of cognitive dysfunction within and across cognitive domains (processing speed, memory, and executive functioning) 6 months after injury in patients with TBI seen at level I trauma centers. This prospective longitudinal cohort study used data from Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) and included patients aged 17 years or older presenting at 18 US level I trauma center emergency departments or inpatient units within 24 hours of head injury, control individuals with orthopedic injury recruited from the same centers, and uninjured friend and family controls. Participants were enrolled between March 2, 2014, and July 27, 2018. Data were analyzed from March 5, 2020, through October 3, 2023. Traumatic brain injury (Glasgow Coma Scale score of 3-15) or orthopedic injury. Performance on standard neuropsychological tests, including premorbid cognitive ability (National Institutes of Health Toolbox Picture Vocabulary Test), verbal memory (Rey Auditory Verbal Learning Test), processing speed (Wechsler Adult Intelligence Scale [4th edition] Processing Speed Index), and executive functioning (Trail Making Test). The sample included 1057 persons with TBI (mean [SD] age, 39.3 [16.4] years; 705 [67%] male) and 327 controls without TBI (mean [SD] age, 38.4 [15.1] years; 222 [68%] male). Most persons with TBI demonstrated performance within 1.5 SDs or better of the control group (49.3% [95% CI, 39.5%-59.2%] to 67.5% [95% CI, 63.7%-71.2%] showed no evidence of impairment). Similarly, 64.4% (95% CI, 54.5%-73.4%) to 78.8% (95% CI, 75.4%-81.9%) of participants demonstrated no evidence of cognitive decline (defined as performance within 1.5 SDs of estimated premorbid ability). For individuals with evidence of either cognitive impairment or decline, diverse profiles of impairment across memory, speed, and executive functioning domains were observed (ie, the prevalence was >0 in each of the 7 combinations of impairment across these 3 cognitive domains for most TBI subgroups). In this cohort study of patients seen at level I trauma centers 6 months after TBI, many patients with TBI demonstrated no cognitive impairment. Impairment was more prevalent in persons with more severe TBI and manifested in variable ways across individuals. The findings may guide future research and treatment recommendations.

Prognosis of comatose patients with reduced EEG montage by combining quantitative EEG features in various domains.

As the frontoparietal network underlies recovery from coma, a limited frontoparietal montage was used, and the prognostic values of EEG features for comatose patients were assessed. Collected with a limited frontoparietal EEG montage, continuous EEG recordings of 81 comatose patients in ICU were used retrospectively. By the 60-day Glasgow outcome scale (GOS), the patients were dichotomized into favorable and unfavorable outcome groups. Temporal-, frequency-, and spatial-domain features were automatically extracted for comparison. Partial correlation analysis was applied to eliminate redundant factors, and multiple correspondence analysis was used to explore discrimination between groups. Prognostic characteristics were calculated to assess the performance of EEG feature-based predictors established by logistic regression. Analyses were performed on all-patients group, strokes subgroup, and traumatic brain injury (TBI) subgroup. By analysis of all patients, raised burst suppression ratio (BSR), suppressed root mean square (RMS), raised power ratio of β to α rhythm (β/α), and suppressed phase-lag index between F3 and P4 (PLI [F3, P4]) were associated with unfavorable outcome, and yielded AUC of 0.790, 0.811, 0.722, and 0.844, respectively. For the strokes subgroup, the significant variables were BSR, RMS, θ/total, θ/δ, and PLI (F3, P4), while for the TBI subgroup, only PLI (F3, P4) was significant. BSR combined with PLI (F3, P4) gave the best predictor by cross-validation analysis in the all-patients group (AUC = 0.889, 95% CI: 0.819-0.960). Features extracted from limited frontoparietal montage EEG served as valuable coma prognostic tools, where PLI (F3, P4) was always significant. Combining PLI (F3, P4) with features in other domains may achieve better performance. A limited-montage EEG coupled with an automated algorithm is valuable for coma prognosis.

Functional Recovery, Symptoms, and Quality of Life 1 to 5 Years After Traumatic Brain Injury

Many level I trauma center patients experience clinical sequelae at 1 year following traumatic brain injury (TBI). Longer-term outcome data are needed to develop better monitoring and rehabilitation services. To examine functional recovery, TBI-related symptoms, and quality of life from 1 to 5 years postinjury. This cohort study enrolled trauma patients across 18 US level I trauma centers between 2014 and 2018. Eligible participants were enrolled within 24 hours of injury and followed up to 5 years postinjury. Data were analyzed January 2023. Mild TBI (mTBI), moderate-severe TBI (msTBI), or orthopedic traumatic controls (OTC). Functional independence (Glasgow Outcome Scale-Extended [GOSE] score 5 or higher), complete functional recovery (GOSE score, 8), better (ie, lower) TBI-related symptom burden (Rivermead Post Concussion Symptoms Questionnaire score of 15 or lower), and better (ie, higher) health-related quality of life (Quality of Life After Brain Injury Scale-Overall Scale score 52 or higher); mortality was analyzed as a secondary outcome. A total 1196 patients were included in analysis (mean [SD] age, 40.8 [16.9] years; 781 [65%] male; 158 [13%] Black, 965 [81%] White). mTBI and OTC groups demonstrated stable, high rates of functional independence (98% to 100% across time). While odds of independence were lower among msTBI survivors, the majority were independent at 1 year (72%), and this proportion increased over time (80% at 5 years; group × year, P = .005; independence per year: odds ratio [OR] for msTBI, 1.28; 95% CI, 1.03-1.58; OR for mTBI, 0.81; 95% CI, 0.64-1.03). For other outcomes, group differences at 1 year remained stable over time (group × year, P ≥ .44). Odds of complete functional recovery remained lower for persons with mTBI vs OTC (OR, 0.39; 95% CI, 0.28-0.56) and lower for msTBI vs mTBI (OR, 0.34; 95% CI, 0.24-0.48). Odds of better TBI-related symptom burden and quality of life were similar for both TBI subgroups and lower than OTCs. Mortality between 1 and 5 years was higher for msTBI (5.5%) than mTBI (1.5%) and OTC (0.7%; P = .02). In this cohort study, patients with previous msTBI displayed increased independence over 5 years; msTBI was also associated with increased mortality. These findings, in combination with the persistently elevated rates of unfavorable outcomes in mTBI vs controls imply that more monitoring and rehabilitation are needed for TBI.

Association of Traumatic Brain Injury With the Risk of Developing Chronic Cardiovascular, Endocrine, Neurological, and Psychiatric Disorders

Increased risk of neurological and psychiatric conditions after traumatic brain injury (TBI) is well-defined. However, cardiovascular and endocrine comorbidity risk after TBI in individuals without these comorbidities and associations with post-TBI mortality have received little attention. To assess the incidence of cardiovascular, endocrine, neurological, and psychiatric comorbidities in patients with mild TBI (mTBI) or moderate to severe TBI (msTBI) and analyze associations between post-TBI comorbidities and mortality. This prospective longitudinal cohort study used hospital-based patient registry data from a tertiary academic medical center to select patients without any prior clinical comorbidities who experienced TBI from 2000 to 2015. Using the same data registry, individuals without head injuries, the unexposed group, and without target comorbidities were selected and age-, sex-, and race-frequency-matched to TBI subgroups. Patients were followed-up for up to 10 years. Data were analyzed in 2021. Mild or moderate to severe head trauma. Cardiovascular, endocrine, neurologic, and psychiatric conditions were defined based on International Classification of Diseases, Ninth Revision (ICD-9) or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10). Associations between TBI and comorbidities, as well as associations between the comorbidities and mortality, were analyzed. A total of 4351 patients with mTBI (median [IQR] age, 45 [29-57] years), 4351 patients with msTBI (median [IQR] age, 47 [30-58] years), and 4351 unexposed individuals (median [IQR] age, 46 [30-58] years) were included in analyses. In each group, 45% of participants were women. mTBI and msTBI were significantly associated with higher risks of cardiovascular, endocrine, neurologic, and psychiatric disorders compared with unexposed individuals. In particular, hypertension risk was increased in both mTBI (HR, 2.5; 95% CI, 2.1-2.9) and msTBI (HR, 2.4; 95% CI, 2.0-2.9) groups. Diabetes risk was increased in both mTBI (HR, 1.9; 95% CI, 1.4-2.7) and msTBI (HR, 1.9; 95% CI, 1.4-2.6) groups, and risk of ischemic stroke or transient ischemic attack was also increased in mTBI (HR, 2.2; 95% CI, 1.4-3.3) and msTBI (HR, 3.6; 95% CI, 2.4-5.3) groups. All comorbidities in the TBI subgroups emerged within a median (IQR) of 3.49 (1.76-5.96) years after injury. Risks for post-TBI comorbidities were also higher in patients aged 18 to 40 years compared with age-matched unexposed individuals: hypertension risk was increased in the mTBI (HR, 5.9; 95% CI, 3.9-9.1) and msTBI (HR, 3.9; 95% CI, 2.5-6.1) groups, while hyperlipidemia (HR, 2.3; 95% CI, 1.5-3.4) and diabetes (HR, 4.6; 95% CI, 2.1-9.9) were increased in the mTBI group. Individuals with msTBI, compared with unexposed patients, had higher risk of mortality (432 deaths [9.9%] vs 250 deaths [5.7%]; P < .001); postinjury hypertension (HR, 1.3; 95% CI, 1.1-1.7), coronary artery disease (HR, 2.2; 95% CI, 1.6-3.0), and adrenal insufficiency (HR, 6.2; 95% CI, 2.8-13.0) were also associated with higher mortality. These findings suggest that TBI of any severity was associated with a higher risk of chronic cardiovascular, endocrine, and neurological comorbidities in patients without baseline diagnoses. Medical comorbidities were observed in relatively young patients with TBI. Comorbidities occurring after TBI were associated with higher mortality. These findings suggest the need for a targeted screening program for multisystem diseases after TBI, particularly chronic cardiometabolic diseases.

Prognostic Value of Hemorrhagic Brainstem Injury on Early Computed Tomography: A TRACK-TBI Study.

Traumatic brainstem injury has yet to be incorporated into widely used imaging classification systems for traumatic brain injury (TBI), and questions remain regarding prognostic implications for this TBI subgroup. To address this, retrospective data on patients from the multicenter prospective Transforming Research and Clinical Knowledge in TBI study were studied. Patients with brainstem and cerebrum injury (BSI+) were matched by age, sex, and admission Glasgow Coma Scale (GCS) score to patients with cerebrum injuries only. All patients had an interpretable head computed tomography (CT) scan from the first 48 hours after injury and a 6-month Glasgow Outcome Scale Extended (GOSE) score. CT scans were reviewed for brainstem lesions and, when present, characterized by location, size, and type (traumatic axonal injury, contusion, or Duret hemorrhage). Clinical, demographic, and outcome data were then compared between the two groups. Mann-Whitney U-tests showed no significant difference in 6-month GOSE scores in patients with BSI+ (mean 2.7) compared with patients with similar but only cerebrum injuries (mean 3.9), although there is a trend (p=0.10). However, subclassification by brainstem lesion type, traumatic axonal injury (mean 4.0) versus Duret hemorrhage or contusion (mean 1.4), did identify a proportion of BSI+ with significantly less favorable outcome (p=0.002). The incorporation of brainstem lesion type (traumatic axonal injury vs. contusion/Duret), along with GCS into a multivariate logistic regression model of favorable outcome (GOSE score 4-8) did show a significant contribution to the prognostication of this brainstem injury subgroup (odds ratio 0.08, 95% confidence interval 0.00-0.67, p=0.01). These findings suggest two groups of patients with brainstem injuries may exist with divergent recovery potential after TBI. These data support the notion that newer CT imaging classification systems may augment traditional clinical measures, such as GCS in identifying those patients with TBI and brainstem injuries that stand a higher chance of favorable outcome.

Relationship between transdiagnostic dimensions of psychopathology and traumatic brain injury (TBI): A TRACK-TBI study.

Neuropsychiatric symptoms are common, comorbid, and often disabling for patients with traumatic brain injury (TBI). Identifying transdiagnostic symptom dimensions post-TBI may help overcome limitations of traditional psychiatric diagnoses and advance treatment development. We characterized the dimensional structure of neuropsychiatric symptoms at 2-weeks postinjury in n = 1,732 TBI patients and n = 238 orthopedic-injured trauma controls (OTC) from the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study. Symptoms were reported on the Brief Symptom Inventory-18, Patient Health Questionnaire-9 Depression checklist, PTSD Checklist for DSM-5, PROMIS Pain Intensity scale, and Insomnia Severity Index. We established a novel factor model of neuropsychiatric symptoms and evaluated how 3 TBI severity strata and OTC patients differed in symptom severity. The final factor model had 6 first-order factors subsumed by 2 second-order factors: Internalizing (encompassing Depression, Anxiety, and Fear) and Somatic symptoms (Sleep, Physical, Pain). Somatic symptoms fit better as a correlated factor of (vs. a lower-order factor within) Internalizing. All symptom dimensions except for Pain were more severe in 1 or more TBI subgroups, as compared to the OTC group. Milder brain injury was generally associated with more severe symptoms, whereas more general injury severity (higher level of care, e.g., emergency department, intensive care unit) was associated with more pain. The findings indicate a broad factor resembling the internalizing factor of general psychopathology in traumatically injured patients, alongside a distinct somatic symptom factor. Brain injury, especially milder brain injury, may exacerbate liabilities toward these symptoms. These neuropsychiatric dimensions may help advance more precision medicine research for TBI. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

817 Robotic Semi-Automated Transcranial Doppler Assessment of Cerebrovascular Autoregulation in Post Concussional Syndrome: Methodological Considerations

Abstract Introduction Post-concussive syndrome (PCS) refers to a constellation of physical, cognitive, and emotional symptoms after traumatic brain injury (TBI). Despite its incidence, the underlying mechanisms are unclear. We hypothesised that impaired cerebral autoregulation (CA) is a contributor. Method A prospective, observational study was integrated into outpatient clinics at a tertiary neurosurgical centre. Data points included: demographics, symptoms (Post-Concussion Symptom Scale [PCSS]), neuropsychological assessment (Cambridge Neuropsychological Test Automated-Battery [CANTAB]) and cerebrovascular metrics (Mxa co-efficient and the transient hyperaemic-response ratio [THRR]) - via transcranial Doppler (TCD), plethysmography and bespoke software (ICM+). Results 12 participants were recruited with 2 excluded after unsuccessful cerebrovascular TCD insonation. 10 participants (5 TBI patients, 5 healthy controls) were included in the analysis (median age 26.5, male:female 7:3). Median PCSS scores were 6/126 (TBI subgroup). Median CANTAB percentiles were 78 (healthy controls) and 25 (TBI). Mxa was calculated for 90% and THRR for 50% of participants. Median study time was 127.5 minutes and feedback (n = 6) highlighted the perceived acceptability of the study. Conclusions This pilot study has demonstrated a feasible and reproducible assessment of PCS and CA metrics (non-invasively) in a real-world setting. By scaling this methodology, we hope to test whether CA changes are correlated with symptomatic PCS in patients post-TBI.

Sleep-Wake Disturbances After Acquired Brain Injury in Children Surviving Critical Care

BackgroundSleep-wake disturbances are underevaluated among children with acquired brain injury surviving critical care. We aimed to quantify severity, phenotypes, and risk factors for sleep-wake disturbances. MethodsWe performed a prospective cohort study of 78 children aged ≥3 years with acquired brain injury within three months of critical care hospitalization. Diagnoses included traumatic brain injury (n = 40), stroke (n = 11), infectious or inflammatory disease (n = 10), hypoxic-ischemic injury (n = 9), and other (n = 8). Sleep Disturbances Scale for Children standardized T scores measured sleep-wake disturbances. Overall sleep-wake disturbances were dichotomized as any total or subscale T score ≥60. Any T score ≥70 defined severe sleep-wake disturbances. Subscale T scores ≥60 identified sleep-wake disturbance phenotypes. ResultsSleep-wake disturbances were identified in 44 (56%) children and were classified as severe in 36 (46%). Sleep-wake disturbances affected ≥33% of patients within each diagnosis and were not associated with severity of illness measures. The most common phenotype was disturbance in initiation and maintenance of sleep (47%), although 68% had multiple concurrent sleep-wake disturbance phenotypes. One third of all patients had preadmission chronic conditions, and this increased risk for sleep-wake disturbances overall (43% vs 21%, P = 0.04) and in the traumatic brain injury subgroup (52% vs 5%, P = 0.001). ConclusionsOver half of children surviving critical care with acquired brain injury have sleep-wake disturbances. Most of these children have severe sleep-wake disturbances independent of severity of illness measures. Many sleep-wake disturbances phenotypes were identified, but most children had disturbance in initiation and maintenance of sleep. Our study underscores the importance of evaluating sleep-wake disturbances after acquired brain injury.

Volume and shape analysis of the Hippocampus and amygdala in veterans with traumatic brain injury and posttraumatic stress disorder.

There is a need to improve the understanding of the neurobiological underpinnings of traumatic brain injury (TBI). Individuals with TBI experience comorbidities such as posttraumatic stress disorder (PTSD) with considerable symptom overlap including depression and hyperarousal, confounding the ability to identify specific TBI-related brain changes. The aims of the current study were to investigate hippocampal and amygdalar volumes in Veterans with TBI with (TBI + PTSD, n = 32) and without (TBI - PTSD, n = 25) PTSD. Shape analysis was employed to reveal any relationship between the hippocampus and depressive symptoms in TBI subgroups. 32 TBI+ PTSD, 25 TBI - PTSD, and 25 age-matched healthy male Veterans underwent an MRI scan on a 3 Tesla scanner and a clinical evaluation. The TBI + PTSD and the TBI + hyperarousal (met criteria for the hyperarousal symptom cluster, regardless of PTSD diagnosis) subgroup had trend-level larger left amygdalar volume than the TBI - PTSD subgroup and the TBI - hyperarousal subgroup, respectively. However, there was no significant difference between the TBI group as a whole and healthy controls (HC). There was a significant negative correlation between the Hamilton Rating Scale for Depression score (HAM-D) and left hippocampal volume and a positive correlation between the HAM-D score and left amygdalar volume in the TBI group. Left hippocampal volume was correlated with the HAM-D score only in the TBI + PTSD and not in TBI - PTSD subgroup. Shape analyses revealed a significant correlation between the HAM-D score and the CA1 and subiculum regions of the left hippocampus. Our results suggest that the amygdala may be a neuroanatomical correlate in mediating PTSD-like symptoms in Veterans with TBI. The results of shape analysis suggest that alterations in the CA1 and subiculum subregions of hippocampus may have a role in depression and PTSD.

Sleep Disorders Following Mild and Moderate Traumatic Brain Injury.

(1) Background: Sleeping disorders are frequently reported following traumatic brain injury (TBI). Different forms of sleeping disorders have been reported, such as sleepiness, insomnia, changes in sleeping latency, and others. (2) Methods: A case-control study with 62 patients who were victims of mild or moderate TBI with previous admissions to Iraqi tertiary neurosurgical centers were enrolled as the first group, and 158 patients with no history of trauma were considered as the control. All were 18 years of age or older, and the severity of the trauma and sleep disorders was assessed. The Pittsburgh sleep quality index was used to assess sleep disorders with average need for sleep per day and average sleep latency were assessed in both groups. Chi-square and t-test calculations were used to compare different variables. (3) Results: 39 patients (24.7%) of the controlled group experienced sleeping disorders compared to TBI group with 45 patients (72.6%), P-value < 0.00001. A total of 42 patients were diagnosed on admission as having a mild degree of TBI (mean GCS 13.22 ± 1.76) and 20 patients were diagnosed with moderate TBI (mean GCS11.05 ± 1.14. 27). A total of 27 (46.28%) patients with mild severity TBI and 18 patients (90%) of moderate severity were considered to experience sleeping disorders, P-value 0.0339. Each of the mild and moderate TBI subgroups show a P-value < 0.00001 compared to the control group. Average sleep hours needed per day for TBI and the control were 8.02 ± 1.04 h and 7.26 ± 0.58 h, respectively, P-value < 0.00001. Average sleep latency for the TBI and the control groups were 13.32 ± 3.16 min and 13.93 ± 3.07 min respectively, P-value 0.065. (4) Conclusion: Sleep disturbances are more common following mild and moderate TBI three months after the injury with more hours needed for sleep per day and no significant difference in sleep latency. Sleep disturbances increase in frequency with the increase in the severity of TBI.

Sub-classifying patients with mild traumatic brain injury: A clustering approach based on baseline clinical characteristics and 90-day and 180-day outcomes.

BackgroundThe current classification of traumatic brain injury (TBI) into “mild”, “moderate”, or “severe” does not adequately account for the patient heterogeneity that still exists within each of these categories. The objective of this study was to identify “sub-groups” of mild TBI (mTBI) patients based on data available at the time of the initial post-TBI patient evaluation and to determine if the sub-grouping correlates with patient outcomes at 90 and 180 days post-TBI.MethodsData from patients in the TRACK-TBI Pilot dataset who had a Glasgow Coma Scale (GCS) score of 13 to 15 at arrival to the Emergency Department and a closed head injury were included. Considering 53 clinical variables that are typically available during the initial evaluation of the patient with mild TBI, sparse heirarchial clustering with cluster quality assessment was used to identify the optimal number of patient sub-groups. Patient sub-groups were then compared for ten outcomes measured at 90 or 180 days post-TBI.ResultsAmongst the 485 patients with mTBI, optimal clustering was based on the inclusion of 12 clinical variables that divided the patients into 5 mild TBI sub-groups. Clinical variables driving the sub-clustering included: gender, employment status, marital status, TBI due to falling, brain CT scan result, systolic blood pressure, diastolic blood pressure, administration of IV fluids in the Emergency Department, alcohol use, tobacco use, history of neurologic disease, and history of psychiatric disease. These 5 mild TBI sub-groups differed in their 90 day and 180 day outcomes within several domains including global outcomes, persistence of TBI-related symptoms, and neuropsychological impairment.ConclusionsSub-groups of patients with mTBI can be identified according to clinical variables that are relatively easy to obtain at the time of initial patient evaluation. A patient’s sub-group assignment is associated with multidimensional patient outcomes at 90 and 180 days. These findings support the notion that there are clinically meaningful subgroups of patients amongst those currently classified as having mTBI.

Magnetic resonance spectroscopy abnormalities in traumatic brain injury: A meta-analysis

Background and purposeDespite traumatic brain injury (TBI) being common, evaluation with imaging remains challenging. Magnetic resonance spectroscopy (MRS) shows promise in detecting changes of brain metabolite concentrations following TBI; however, currently there are only small studies available without conclusive evidence of the technique's efficacy. The purpose of this systematic review and meta-analysis was to evaluate the association between TBI and MRS metabolite changes. Materials & methodsA comprehensive literature search was performed looking for studies reporting brain metabolite concentrations in both TBI and control subjects. Included studies reported values for both adult TBI and control subjects. Cumulative and subgroup meta-analyses were performed using a random effects model. ResultsThe literature search returned an initial 898 manuscripts, of which 36 (which included 748 unique subjects) met study criteria. Cumulatively, NAA/Cr ratios in TBI patients showed a significant decrease as compared to controls (standardized mean deviation [SMD]=−0.88, P<0.0001). When broken into subgroups by severity, the severe and mixed TBI subgroups showed decreases, but the mild TBI (mTBI) subgroup did not. When stratified by time, a significant decrease was seen in the subacute and chronic phases but not the acute phase. Cumulative post-TBI Cho/Cr levels were increased compared to controls (SMD=0.69, P=0.0002). Significant changes were seen in all subgroups except the mild and mixed mTBI subgroups and the acute phase subgroup. ConclusionCurrent evidence shows that MRS is able to detect changes to metabolites following TBI, but not in patients with mTBI or in the acute stage.

Moderate TBI increases susceptibility to rewarding effects of a subthreshold dose of cocaine in mice

To describe Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans who underwent the Comprehensive Traumatic Brain Injury Evaluation (CTBIE), differences between the traumatic brain injury (TBI) and non-TBI subgroups, and factors associated with return to productivity (RTP).Retrospective medical record review.Medical center.Medical records of OEF/OIF veterans (N=236) who underwent the CTBIE between 2009 and 2013.Not applicable.Demographic characteristics, injury history, clinical presentation, and factors associated with RTP.Veteran sample included 90.7% men, was 45.3% white and 34.7% black, with half of Hispanic origin, and had a mean age of 33 years. The mean time since injury was approximately 4 years. Reported symptoms were high, with >90% reporting anxiousness, irritability, sleep difficulty, forgetfulness, and headaches. TBI diagnosis was found in 163 veterans (69%). The TBI subgroup was younger (TBI: 32.5y vs non-TBI: 34.9y; P=.02), reported a greater number of injuries (P<.001), and had significantly higher rates of half of the reported symptoms. Greatest differences were noted with forgetfulness (TBI: 95.7% vs non-TBI: 79.5%; P<.001), poor concentration (TBI: 90.2% vs non-TBI: 76.7%; P=.007), and headaches (TBI: 93.9% vs non-TBI: 83.6%; P=.014). RTP was 60.6% for the total veteran population. Factors associated with RTP were race (white) (odds ratio [OR], 2.00; 95% confidence interval [CI], 1.13–3.55; P=.018), sensitivity to light (OR, 2.58; 95% CI, 1.17–5.66; P=.018), and fatigue (OR, 3.68; 95% CI, 1.51–8.95; P=.004). Veterans that did RTP were 3 times less likely to report depression (OR, .32; 95% CI, .12–.85; P=.022).Veterans reported a substantial number of lingering symptoms, with a higher prevalence in veterans with TBI. Veterans with reported depression were less likely to RTP. Future research should focus on the relation between depression and non-RTP and the effectiveness of Department of Veterans Affairs services.

Long-Term Neurobehavioral Symptoms and Return to Productivity in Operation Enduring Freedom/Operation Iraqi Freedom Veterans With and Without Traumatic Brain Injury

ObjectiveTo describe Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans who underwent the Comprehensive Traumatic Brain Injury Evaluation (CTBIE), differences between the traumatic brain injury (TBI) and non-TBI subgroups, and factors associated with return to productivity (RTP). DesignRetrospective medical record review. SettingMedical center. ParticipantsMedical records of OEF/OIF veterans (N=236) who underwent the CTBIE between 2009 and 2013. InterventionsNot applicable. Main Outcome MeasuresDemographic characteristics, injury history, clinical presentation, and factors associated with RTP. ResultsVeteran sample included 90.7% men, was 45.3% white and 34.7% black, with half of Hispanic origin, and had a mean age of 33 years. The mean time since injury was approximately 4 years. Reported symptoms were high, with >90% reporting anxiousness, irritability, sleep difficulty, forgetfulness, and headaches. TBI diagnosis was found in 163 veterans (69%). The TBI subgroup was younger (TBI: 32.5y vs non-TBI: 34.9y; P=.02), reported a greater number of injuries (P<.001), and had significantly higher rates of half of the reported symptoms. Greatest differences were noted with forgetfulness (TBI: 95.7% vs non-TBI: 79.5%; P<.001), poor concentration (TBI: 90.2% vs non-TBI: 76.7%; P=.007), and headaches (TBI: 93.9% vs non-TBI: 83.6%; P=.014). RTP was 60.6% for the total veteran population. Factors associated with RTP were race (white) (odds ratio [OR], 2.00; 95% confidence interval [CI], 1.13–3.55; P=.018), sensitivity to light (OR, 2.58; 95% CI, 1.17–5.66; P=.018), and fatigue (OR, 3.68; 95% CI, 1.51–8.95; P=.004). Veterans that did RTP were 3 times less likely to report depression (OR, .32; 95% CI, .12–.85; P=.022). ConclusionsVeterans reported a substantial number of lingering symptoms, with a higher prevalence in veterans with TBI. Veterans with reported depression were less likely to RTP. Future research should focus on the relation between depression and non-RTP and the effectiveness of Department of Veterans Affairs services.

Subacute Pain after Traumatic Brain Injury Is Associated with Lower Insular N-Acetylaspartate Concentrations.

Persistent pain is experienced by more than 50% of persons who sustain a traumatic brain injury (TBI), and more than 30% experience significant pain as early as 6 weeks after injury. Although neuropathic pain is a common consequence after CNS injuries, little attention has been given to neuropathic pain symptoms after TBI. Magnetic resonance spectroscopy (MRS) studies in subjects with TBI show decreased brain concentrations of N-acetylaspartate (NAA), a marker of neuronal density and viability. Although decreased brain NAA has been associated with neuropathic pain associated with spinal cord injury (SCI) and diabetes, this relationship has not been examined after TBI. The primary purpose of this study was to test the hypothesis that lower NAA concentrations in brain areas involved in pain perception and modulation would be associated with greater severity of neuropathic pain symptoms. Participants with TBI underwent volumetric MRS, pain and psychosocial interviews. Cluster analysis of the Neuropathic Pain Symptom Inventory subscores resulted in two TBI subgroups: The Moderate Neuropathic Pain (n = 17; 37.8%), with significantly (p = 0.038) lower insular NAA than the Low or no Neuropathic Pain group (n = 28; 62.2%), or age- and sex-matched controls (n = 45; p < 0.001). A hierarchical linear regression analysis controlling for age, sex, and time post-TBI showed that pain severity was significantly (F = 11.0; p < 0.001) predicted by a combination of lower insular NAA/Creatine (p < 0.001), lower right insular gray matter fractional volume (p < 0.001), female sex (p = 0.005), and older age (p = 0.039). These findings suggest that neuronal dysfunction in brain areas involved in pain processing is associated with pain after TBI.