Complicated Mild Traumatic Brain Injury Research Articles

ASA-score is associated with 90-day mortality after complicated mild traumatic brain injury – a retrospective cohort study

PurposeThis study explores the association of the American Society of Anesthesiologists (ASA) score with 90-day mortality in complicated mild traumatic brain injury (mTBI) patients, and in trauma patients without a TBI.MethodsThis retrospective study was conducted using a cohort of trauma patients treated at a level III trauma center in Stockholm, Sweden from January to December 2019. The primary endpoint was 90-day mortality. The population was identified using the Swedish Trauma registry. The Trauma and Injury Severity Score (TRISS) was used to estimate the likelihood of survival. Trauma patients without TBI (NTBI) were used for comparison. Data analysis was conducted using R software, and statistical analysis included univariate and multivariate logistic regression.ResultsA total of 244 TBI patients and 579 NTBI patients were included, with a 90-day mortality of 8.2% (n = 20) and 5.4% (n = 21), respectively. Deceased patients in both cohorts were generally older, with greater comorbidities and higher injury severity. Complicated mTBI constituted 97.5% of the TBI group. Age and an ASA score of 3 or higher were independently associated with increased mortality risk in the TBI group, with odds ratios of 1.04 (95% 1.00–1.09) and 3.44 (95% CI 1.10–13.41), respectively. Among NTBI patients, only age remained a significant mortality predictor. TRISS demonstrated limited predictive utility across both cohorts, yet a significant discrepancy was observed between the outcome groups within the NTBI cohort.ConclusionThis retrospective cohort study highlights a significant association between ASA score and 90-day mortality in elderly patients with complicated mTBI, something that could not be observed in comparative NTBI cohort. These findings suggest the benefit of incorporating ASA score into prognostic models to enhance the accuracy of outcome prediction models in these populations, though further research is warranted.

Derivation of the Quebec Brain Injury Categories for complicated mild traumatic brain injuries.

Approximately 10% of patients with mild traumatic brain injury (TBI) present with intracranial bleeding, and only 3.5% eventually require neurosurgical intervention, which often necessitates interhospital transfer. Better guidelines and recommendations are needed to manage complicated mild TBI in the emergency department (ED). The main objective of this study was to derive a clinical decision rule, the Quebec Brain Injury Categories (QueBIC), to predict the risk of adverse outcomes for complicated mild TBI in the ED. The secondary objective was to compare the QueBIC's performance with those of other existing guidelines. The authors conducted a retrospective multicenter cohort study in 3 level I trauma centers. Consecutive patients with complicated mild TBI (Glasgow Coma Scale [GCS] score 13-15) who were aged ≥ 16 years were included. The primary outcome was a combination of neurosurgical intervention, mild TBI-related death, and clinical deterioration. Statistical analyses included set covering machine analyses. In total, 477 patients were included in the study. The mean age was 62.9 years, and 68.1% were male. The algorithm classified patients into three risk categories (low, moderate, and high risk). The high-risk group (128 patients) (subdural hemorrhage [SDH] width > 7 mm or any midline shift) presented a sensitivity of 84% (95% CI 71%-93%) and a specificity of 80% (95% CI 76%-84%) to detect neurosurgical intervention and mild TBI-related death, leaving 8 undetected cases. Patients in the moderate-risk group (169 patients) had at least 1 variable: SDH width > 4 mm, initial GCS score ≤ 14, > 1 intraparenchymal hemorrhage, or intraparenchymal hemorrhage width > 4 mm. The combined QueBIC high- and moderate-risk category had a sensitivity of 100% (95% CI 63%-100%) and a specificity of 53% (95% CI 47%-58%) to detect mild TBI-related death or neurosurgical intervention. The sensitivity and specificity values for clinical deterioration when no death or neurosurgical intervention occurred were 81% (95% CI 64%-93%) and 44% (95% CI 39%-49%), respectively. The remaining 180 patients (37.7%) did not meet any high-risk or moderate-risk criteria and were considered low risk. None had neurosurgical intervention or mild TBI-related death. Only 6 (3.3%) low-risk patients showed clinical deterioration. QueBIC is a safe and effective tool to guide the management of patients presenting to the ED with complicated mild TBI. It accurately identifies patients at low risk for specialized neurotrauma or neurosurgical care. Further validation is required before its use in EDs.

Accelerated Aging after Traumatic Brain Injury: An ENIGMA Multi-Cohort Mega-Analysis.

The long-term consequences of traumatic brain injury (TBI) on brain structure remain uncertain. Given evidence that a single significant brain injury event increases the risk of dementia, brain-age estimation could provide a novel and efficient indexing of the long-term consequences of TBI. Brain-age procedures use predictive modeling to calculate brain-age scores for an individual using structural magnetic resonance imaging (MRI) data. Complicated mild, moderate, and severe TBI (cmsTBI) is associated with a higher predicted age difference (PAD), but the progression of PAD over time remains unclear. We sought to examine whether PAD increases as a function of time since injury (TSI) and if injury severity and sex interacted to influence this progression. Through the ENIGMA Adult Moderate and Severe (AMS)-TBI working group, we examine the largest TBI sample to date (n = 343), along with controls, for a total sample size of n = 540, to replicate and extend prior findings in the study of TBI brain age. Cross-sectional T1w-MRI data were aggregated across 7 cohorts, and brain age was established using a similar brain age algorithm to prior work in TBI. Findings show that PAD widens with longer TSI, and there was evidence for differences between sexes in PAD, with men showing more advanced brain age. We did not find strong evidence supporting a link between PAD and cognitive performance. This work provides evidence that changes in brain structure after cmsTBI are dynamic, with an initial period of change, followed by relative stability in brain morphometry, eventually leading to further changes in the decades after a single cmsTBI. ANN NEUROL 2024;96:365-377.

Mood Tracker: A Randomized Controlled Trial of a Self-Monitoring Intervention for Emotional Distress After Traumatic Brain Injury.

Persons with traumatic brain injury (TBI) frequently experience emotional distress (ED) manifested in anxiety and depression. However, they may not access mental health services due to external (eg, access, transportation, and cost) or internal (eg, stigma and discomfort with traditional counseling) barriers. Based on substantial literature indicating that self-monitoring can ameliorate several health conditions, we conducted a randomized, parallel group, wait-list control (WLC) trial of a self-monitoring intervention to decrease ED after TBI. Community in the southwestern United States. Persons with medically documented complicated mild, moderate, and severe TBI. About 127 participants were randomized in blocks of 6 to an active treatment (AT) group, wherein they completed multiple assessments of ED each week over a 6-week period via a smartphone app, or a WLC group in a parallel group, controlled trial. Participants received weekly support calls to promote self-monitoring of ED using ecological momentary assessment. ED (Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7), Satisfaction with Life Scale, and Participation Assessment with Recombined Tools-Objective. Analysis of the primary study outcome at 6weeks after initiation of treatment for the AT group did not demonstrate that self-monitoring was effective in decreasing ED as compared to the WLC group. Brief support calls made weekly to promote compliance with self-monitoring were effective in achieving the target number of self-assessments. About 80% of support calls lasted less than 5minutes. Greater ED was associated with lower life satisfaction and lower participation indicating the importance of addressing ED in persons with TBI. Additional work is needed to develop nontraditional interventions to circumvent barriers that prevent persons with TBI from accessing care for ED. Brief support calls may be an effective, low-cost intervention to improve compliance with self-monitoring or self-management interventions.

249 Interprofessional Consultation to Reduce Unnecessary Transfers of Complicated Mild TBI to Tertiary Referral Centers

INTRODUCTION: The neurosurgical intervention rate for complicated mild traumatic brain injury (cmTBI) is less than 1%. However, the absence of transfer guidelines and fear of malpractice results in unnecessary transfers of cmTBI patients to tertiary referral centers. METHODS: Between April 2021 and March 2023, we implemented a Tele-TBI at three community hospitals for cmTBI patients seen in the emergency department (ED). An interprofessional telehealth-based consultation between emergency medicine and neurosurgery determined if a patient needed to be transferred to the Level-1Trauma Center or could be cared for at the community hospital. A retrospectively chart review was used to determine if transfers were unnecessary. Transfer rates were compared for patients from hospitals with and without the Tele-TBI protocol. RESULTS: Out of 822 cmTBI patients seen in our ED, 73% (n = 602) were transferred from other hospitals. The mean age of transferred patients was 67.5 (±19.9) and median GCS was 15. During this time, 128 Tele-TBI consultations were performed. The mean age was 75.7 (±16.2), and median GCS was 15. The overall transfer rate was decreased by 89% (n = 15/128) when Tele-TBI consultations were initiated. Tele-TBI-enabled hospitals had significantly fewer (p < 0.001) unindicated transfers (28.7%, n = 66 versus 71.3% n = 164) and led to fewer (p = 0.003) transferred patients discharged directly from the Level-1Trauma Center ED (28.6%, n = 66 versus 72.3%, n = 173). ICU admissions and frequency of neurosurgical intervention did not differ between hospitals with or without tele-TBI implementation. CONCLUSIONS: Interprofessional telehealth-based consultation can effectively triage patients with cmTBI presenting to community hospitals, leading to fewer unnecessary transfers with similar rates of ICU admissions and neurosurgical interventions.

Disparities between Native Americans and Whites in trajectories of functional independence and life satisfaction over the 5 years after traumatic brain injury.

Traumatic brain injury (TBI) can lead to impairments in motor and cognitive function and reduced life satisfaction. TBI is one of the leading causes of death and disability worldwide and disproportionately affects Native Americans, who have the highest rates of TBI among all races in the United States and elevated likelihood for fatality and severe complications. This study investigated whether disparities in functional and life satisfaction outcomes exist longitudinally over the 5 years after complicated mild, moderate, or severe TBI between Native Americans and White individuals; it further explored which demographic and injury-related covariates account for them. The current study used a subsample of the national TBI Model Systems Database of 80 demographically and injury-severity matched Native American and White pairs (total n = 160). A series of longitudinal hierarchical linear models found that Native Americans experienced significantly lower Functional Independence Measure Cognitive and Motor trajectories than Whites; however, life satisfaction was comparable. Native Americans had declining cognitive function over time relative to a slight increase in White individuals. This differential movement dissipated with the addition of employment status at the time of injury and type of health insurance. These results demonstrate a profound need to further investigate the cultural and contextual variables unique to Native Americans that underlie these differences and highlight the importance of culturally responsive treatment and rehabilitation in bridging the gap in recovery. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Clinical Outcomes After Traumatic Brain Injury and Exposure to Extracranial Surgery

Traumatic brain injury (TBI) is associated with persistent functional and cognitive deficits, which may be susceptible to secondary insults. The implications of exposure to surgery and anesthesia after TBI warrant investigation, given that surgery has been associated with neurocognitive disorders. To examine whether exposure to extracranial (EC) surgery and anesthesia is related to worse functional and cognitive outcomes after TBI. This study was a retrospective, secondary analysis of data from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study, a prospective cohort study that assessed longitudinal outcomes of participants enrolled at 18 level I US trauma centers between February 1, 2014, and August 31, 2018. Participants were 17 years or older, presented within 24 hours of trauma, were admitted to an inpatient unit from the emergency department, had known Glasgow Coma Scale (GCS) and head computed tomography (CT) status, and did not undergo cranial surgery. This analysis was conducted between January 2, 2020, and August 8, 2023. Participants who underwent EC surgery during the index admission were compared with participants with no surgery in groups with a peripheral orthopedic injury or a TBI and were classified as having uncomplicated mild TBI (GCS score of 13-15 and negative CT results [CT- mTBI]), complicated mild TBI (GCS score of 13-15 and positive CT results [CT+ mTBI]), or moderate to severe TBI (GCS score of 3-12 [m/sTBI]). The primary outcomes were functional limitations quantified by the Glasgow Outcome Scale-Extended for all injuries (GOSE-ALL) and brain injury (GOSE-TBI) and neurocognitive outcomes at 2 weeks and 6 months after injury. A total of 1835 participants (mean [SD] age, 42.2 [17.8] years; 1279 [70%] male; 299 Black, 1412 White, and 96 other) were analyzed, including 1349 nonsurgical participants and 486 participants undergoing EC surgery. The participants undergoing EC surgery across all TBI severities had significantly worse GOSE-ALL scores at 2 weeks and 6 months compared with their nonsurgical counterparts. At 6 months after injury, m/sTBI and CT+ mTBI participants who underwent EC surgery had significantly worse GOSE-TBI scores (B = -1.11 [95% CI, -1.53 to -0.68] in participants with m/sTBI and -0.39 [95% CI, -0.77 to -0.01] in participants with CT+ mTBI) and performed worse on the Trail Making Test Part B (B = 30.1 [95% CI, 11.9-48.2] in participants with m/sTBI and 26.3 [95% CI, 11.3-41.2] in participants with CT+ mTBI). This study found that exposure to EC surgery and anesthesia was associated with adverse functional outcomes and impaired executive function after TBI. This unfavorable association warrants further investigation of the potential mechanisms and clinical implications that could inform decisions regarding the timing of surgical interventions in patients after TBI.

34 Severity of Traumatic Brain Injury Predicts Neurobehavioral Outcomes and White Matter Microstructure

Objective:Pediatric traumatic brain injury (TBI) is the leading cause of disability in children under the age of 15, often resulting in executive function deficits and poor behavioral outcomes. Damage to white matter tracts may be a driving force behind these difficulties. We examined if whether 1) greater TBI severity was associated with worse neurobehavioral outcome, 2) greater TBI severity was associated with tract-based white matter microstructure, and 3) worse neurobehavioral outcome was associated with white matter microstructure.Participants and Methods:Twelve children with complicated-mild TBI (cmTBI; Mage=12.59, nmale=9), 17 with moderate-to-severe TBI (msTBI; Mage =11.50, nmale=11), and 21 with orthopedic injury (OI; Mage =11.60, nmale=16), 3.94 years post injury on average, were recruited from a large midwestern children’s hospital with a Level 1 Trauma Center. Parents completed the Behavior Rating Inventory of Executive Function (BRIEF) and Child Behavior Checklist (CBCL) while children completed 64-direction diffusion tensor imaging in a Siemens 3T scanner. White matter microstructure was quantified with FMRIB’s Diffusion Toolbox (FSLv6.0.4). Tract-Based Spatial Statistics computed fractional anisotropy (FA) and mean diffusivity (MD) for the cingulum bundle (CB), inferior fronto-occipital fasciculus (IFOF), superior longitudinal fasciculus (SLF), and uncinate fasciculus (UF), bilaterally.Results:Group differences were assessed using one-way ANOVA. Children with msTBI were rated as having worse Sluggish Cognitive Tempo on the CBCL than children with cmTBI and OI (p=.02, eta2=.143); no other parent-rated differences reached significance. Group differences were found in left SLF FA (p=.031; msTBI<cmTBI=OI) and approached significance in left UF FA (p=.062, eta2=.114; msTBI<OI). Group differences were also found in right IFOF MD (p=.048; msTBI>OI) and left SLF MD (p=.013; msTBI>cmTBI=OI). Bivariate correlations assessed cross-domain associations. Higher left IFOF FA was associated with better BRIEF Metacognitive Skills (r=-.301, p=.030) and CBCL School Competence (r=.280; p=.049). Higher left SLF FA was associated with better BRIEF Behavioral Regulation and Metacognitive Skills (r=-.331, p=.017 and r=-.291, p=.036, respectively), and CBCL School Competence and Attention Problems (r=.398, p=.004 and r=-.435, p=.001, respectively). Similarly, higher right UF FA was broadly associated with better neurobehavioral outcomes, including Behavioral Regulation and Metacognitive Skills (r=-.324, p=.019 and r=-.359, p=.009, respectively), and School Competence, Attention Problems, and Sluggish Cognitive Tempo (r=.328, p=.020, r=-.398, p=.003, and r=-.356, p=.010, respectively). Higher right CB MD was associated with worse Behavioral Regulation (r=.327, p=.018) and more Attention Problems (r=.278, p=.046); higher left and right SLF MD was associated with Sluggish Cognitive Tempo (r=.363, p=.008, r=.408, p=.003, respectively).Conclusions:Children with TBI, particularly msTBI, were rated as having cognitive slowing; while other anticipated group differences in neurobehavioral outcomes were not found, this appears driven by milder difficulties in cmTBI and OI groups. In fact, across CBCL and BRIEF subscales, children with msTBI were rated as approaching or exceeding a full standard deviation deficit based on normative data. TBI severity was also associated with white matter microstructure and cross-domain associations linked microstructure with observable neurobehavioral morbidities, suggesting a possible mechanism post-injury. Future longitudinal studies would be useful to examine the temporal evolution of deficits.

1 Social Brain Network Connectivity Relates to Social and Adaptive Outcomes Following Pediatric Traumatic Brain Injury

Objective:Traumatic brain injury (TBI) is a prevalent cause of long-term morbidity in children and adolescents and can lead to persistent difficulties with social and behavioral function. TBI may impact brain structures that support social cognition, social perception, and day-to-day social interactions—termed the social brain network (SBN). We examined differences in links among the SBN and regions of interest from other neural networks thought to support social outcomes, i.e., the default mode network (DMN) and salience network (SN). Furthermore, we examined how differences in co-activation among the SBN and these other key networks were associated with ratings of social and day-to-day adaptive outcomes.Participants and Methods:Participants included children and adolescents with moderate to severe TBI (msTBI; n=11, Mage=11.78, 6 male), complicated-mild TBI (cmTBI; n=12, Mage=12.59, 9 male), and orthopedic injury (OI; n=22, Mage=11.69, 15 male). Participants underwent resting-state functional MRI on a 3Tesla Siemens Prisma scanner. Parents rated their child’s social and adaptive function on the Child Behavior Checklist (CBCL) and Adaptive Behavior Assessment System-Third Edition (ABAS-3). Resting-state connectivity was assessed using the CONN Toolbox, including preprocessing, denoising, and alignment to the participants’ processed T1 MPRAGE sequence followed by seed-to-voxel analysis using a SBN mask and targeted regions of interest within the DMN and SN. Individual-level r-to-z correlations were extracted from resulting clusters of co-activation with the SBN mask and exported into SPSSv28.0 for integration with behavioral data.Results:One-way ANOVAs used to examine group differences in social and adaptive outcome revealed significant group differences in CBCL Social Competence (F=4.49, p=.019) and all composite scores on the ABAS-3 (Fs=3.78 to 5.17, ps=.031 to .010). In each domain, children with msTBI were rated as having elevated difficulties relative to cmTBI or OI, whereas cmTBI and OI groups did not differ. Connectivity also differed significantly between groups, with children with OI demonstrating greater connectivity between the SBN and the anterior cingulate cortex of the SN (t=5.19, p(FDR)<.0001) and posterior cingulate cortex of the DMN (f=4.30, p(FDR)<.001) than children with msTBI. Children with cmTBI also showed greater connectivity between the SBN and left temporal pole of the DMN (t=7.45, p(FDR)<.000001) than children with msTBI. Degree of connectivity between the SBN and posterior cingulate was significantly positively correlated across all domains of adaptive function (rs=.451 to .504, ps=.010 to .003), whereas degree of connectivity between the SBN and left temporal pole was strongly positively related to Social Competence (a=.633, p=.006) and conceptual adaptive skills on the ABAS (A=.437, p=.037).Conclusions:Our findings provide insights into the neural substrates of social and adaptive morbidity after pediatric TBI, particularly msTBI, by linking alterations in connectivity among the SBN, DMN, and SN with measures of social and adaptive outcome. While the posterior cingulate was broadly associated with adaptive outcome, the temporal pole was particularly strongly associated with social competence. This may reflect the diverse functions and high degree of interconnectivity of the posterior cingulate, which contributes to various cognitive and attentional processes, relative to the strong amygdala/limbic connections of the temporal pole.

White Matter Metabolite Ratios Predict Cognitive Outcome in Pediatric Traumatic Brain Injury.

The prognostic ability of global white matter and gray matter metabolite ratios following pediatric traumatic brain injury (TBI) and their relationship to 12-month neuropsychological assessments of intelligence quotient (IQ), attention, and memory is presented. Three-dimensional proton magnetic resonance spectroscopic imaging (MRSI) in pediatric subjects with complicated mild (cMild), moderate, and severe TBI was acquired acutely (6-18 days) and 12 months post-injury and compared to age-matched typically developing adolescents. A global linear regression model, co-registering MRSI metabolite maps with 3D high-resolution magnetic resonance images, was used to identify longitudinal white matter and gray matter metabolite ratio changes. Acutely, gray matter NAA/Cr, white matter NAA/Cr, and white matter NAA/Cho ratios were significantly lower in TBI groups compared to controls. Gray matter NAA/Cho was reduced only in the severe TBI group. At 12 months, all metabolite ratios normalized to control levels in each of the TBI groups. Acute gray matter and white matter NAA ratios were significantly correlated to 12-month assessments of IQ, attention, and memory. These findings suggest that whole brain gray matter and white matter metabolite ratios reflect longitudinal changes in neuronal metabolism following TBI, which can be used to predict neuropsychological outcomes in pediatric subjects.

Cognitive outcome following complicated mild Traumatic Brain Injury: A literature review and meta-analysis.

Cognitive outcome for mild TBI with positive brain imaging (complicated MTBI) was compared with that for mild TBI with normal imaging (uncomplicated MTBI) and moderate to severe TBI using meta-analysis. Twenty-three studies utilising objective neurocognitive tests were included in the analysis. At less than 3 months post-injury, complicated MTBI was associated with poorer cognitive outcomes than uncomplicated MTBI but deficits were not comparable to those with moderate-severe TBI. After 3 months post-injury a similar pattern was detected. Beyond 3 months, relative deficits in complicated MTBI to those with uncomplicated MTBI were present in processing speed, memory, executive function and language, though the latter may be due to reduced semantic fluency. The effect size of deficits in these domains was more marked in moderate-severe TBI. The available data supports the use of complicated MTBI as a distinct classification in the prediction of cognitive outcome. The size of cognitive deficit in complicated MTBI was small and unlikely to cause significant disability. However, complicated MTBI is a broad category encompassing individuals who may differ markedly in the nature and extent of intracranial imaging abnormality and further studies are warranted. Limitations of the available studies include small, selected samples, variations in TBI severity classification, absence of validity ('effort') testing, differing imaging methodology and lack of long-term follow up.

Predicting Complicated Mild Traumatic Brain Injury in Adolescent Trauma to Enhance Clinical Decisions in Imaging.

The Pediatric Emergency Care Applied Research Network (PECARN) traumatic brain injury algorithm is used to identify children at low risk of clinically significant traumatic brain injuries to reduce computed tomography (CT) exposure. Adapting PECARN rules based on population-specific risk stratification has been suggested to improve diagnostic accuracy. This study sought to identify center-specific patient variables, beyond PECARN rules, that may enhance the identification of patients requiring neuroimaging. This single-center, retrospective cohort study was conducted from July 1, 2016, to July 1, 2020, in a Southwestern U.S. Level II pediatric trauma center. The inclusion criteria were adolescents (10-15 years), Glasgow Coma Scale (13-15), with a confirmed mechanical blow to the head. Patients without a head CT were excluded. Logistic regression was performed to identify additional complicated mild traumatic brain injury predictor variables beyond the PECARN. There were 136 patients studied; 21 (15%) presented with a complicated mild traumatic brain injury. Relative to motorcycle collision or all-terrain vehicle trauma (odds ratio [OR] 211.75, 95% confidence interval, CI [4.51, 9931.41], p < .001), an unspecified mechanism (OR 42.0, 95% CI [1.30, 1350.97], p = .03) and consult activation (OR 17.44, 95% CI [1.75, 173.31], p = .01) were significantly associated with complicated mild traumatic brain injury. We identified additional factors associated with complex mild traumatic brain injury, including motorcycle collision and all-terrain vehicle trauma, unspecified mechanism, and consult activation that are not in the PECARN imaging decision rule. Adding these variables may aid in determining the need for appropriate CT scanning.

Comparisons of electrophysiological markers of impaired executive attention after traumatic brain injury and in healthy aging

Executive attention impairments are a persistent and debilitating consequence of traumatic brain injury (TBI). To make headway towards treating and predicting outcomes following heterogeneous TBI, cognitive impairment specific pathophysiology first needs to be characterized. In a prospective observational study, we measured EEG during the attention network test aimed at detecting alerting, orienting, executive attention and processing speed. The sample (N = 110) of subjects aged 18–86 included those with and without traumatic brain injury: n = 27, complicated mild TBI; n = 5, moderate TBI; n = 10, severe TBI; n = 63, non-brain-injured controls. Subjects with TBI had impairments in processing speed and executive attention. Electrophysiological markers of executive attention processing in the midline frontal regions reveal that, as a group, those with TBI and elderly non-brain-injured controls have reduced responses. We also note that those with TBI and elderly controls have responses that are similar for both low and high-demand trials. In subjects with moderate-severe TBI, reductions in frontal cortical activation and performance profiles are both similar to that of controls who are ∼4 to 7 years older. Our specific observations of frontal response reductions in subjects with TBI and in older adults is consistent with the suggested role of the anterior forebrain mesocircuit as underlying cognitive impairments. Our results provide novel correlative data linking specific pathophysiological mechanisms underlying domain-specific cognitive deficits following TBI and with normal aging. Collectively, our findings provide biomarkers that may serve to track therapeutic interventions and guide development of targeted therapeutics following brain injuries.

Cross-Walk Comparison of the DVBIC-TBICoE and LIMBIC-CENC Combat-Related Concussion Prospective Longitudinal Study Datasets

ObjectiveTo describe and compare cohorts between 2 large, longitudinal, federally-funded TBI studies of Service members and veterans across demographic, self-report, and neuropsychological variables. DesignAnalysis of data from the DVBIC-TBICoE and LIMBIC-CENC prospective longitudinal studies (PLS). SettingRecruitment locations spanning Department of Defense and Veterans Affairs hospitals across the U.S. Participants1463 participants (N=1463) enrolled in the DVBIC-TBICoE study and divided among non-injured (NIC) (n=191), injured control (IC) (n=349), mild TBI (mTBI) (n=682), and (severe, moderate, penetrating, and complicated mild traumatic brain injury (smcTBI) (n=241) subgroups. 1550 participants enrolled in the LIMBIC-CENC study and divided between IC (n=285) and mTBI (n=1265) subgroups. IC and mTBI study groups were compared across demographic and military characteristics, self-reported symptoms, and neuropsychological test scores. InterventionsNone. Main Outcome MeasuresNeurobehavioral Symptom Inventory, PTSD Checklist-Military Version, TBI quality of life, Test of Premorbid Functioning, Wechsler Adult Intelligence Scale-IV Visual Puzzles, Symbol Search, Coding, Letter-Number Sequencing, and Digit Span, Trail Making Test, Delis-Kaplan Executive Functioning System Verbal Fluency, Letter Fluency, and Category Fluency, California Verbal Learning Test-II, and Grooved Pegboard. ResultsCompared with DVBIC-TBICoE, LIMBIC-CENC participants have higher enrollment age, education level, proportion of Black race, and time from injury as well as less combat deployments and are less likely to be married. The distribution of military service branches also differed. Further, symptom profiles differed between cohorts. LIMBIC-CENC participants endorsed higher posttraumatic stress disorder symptomatology. DVBIC-TBICoE study IC participants endorsed higher somatosensory and vestibular symptoms (medium effect sizes). Other symptom measure differences had very small effect sizes (≤0.2). Differences were found on many cognitive test results, but are difficult to interpret given the demographic differences and generally very small effect sizes. ConclusionsThe heavy use of National Institutes of Health common data elements in both studies and collaboration with the DVBIC-TBICoE study team on development of the LIMBIC-CENC assessment battery enabled this comparative analysis. Results highlight unique differences in study cohorts and add perspective and interpretability for assimilating past and future findings.

Sport participation among children with complicated mild traumatic brain injury.

Complicated mild traumatic brain injury (C-mTBI) represents mTBI with positive trauma-related radiographic findings, such as hematoma. It is estimated that 7.5% of all pediatric mTBIs meet these criteria. There is a paucity of research on return to sports in children with C-mTBI. To examine children with C-mTBI, mTBI with skull fracture (mTBI-SF) only and mTBI in relation to sport participation and factors associated with repeated injury. Cross-sectional survey. Level I pediatric trauma center. Parents of children who were 5-18 years of age at the time of injury who sustained C-mTBI or mTBI from 2010 to 2013. Not applicable. Sports participation characteristics before and after injury in children with C-mTBI and mTBI as a function of degree and length of recovery. Repeat mTBI after the index injury was also examined. Of 247 children who participated in sports preinjury (27.5% with C-mTBI and 9.7% with mTBI-SF), 95.1% returned to sports. There was no significant difference by mTBI type regarding participation in any sports (p =.811) nor with high-risk sports (p =.128). C-mTBI but not mTBI-SF (versus mTBI) was associated with lower odds of sustaining a repeat mTBI (odds ratio=0.30, p=.045). Waiting longer (>3months compared to <1month) to return to contact sports was associated with lower odds of sustaining a repeat mTBI (odds ratio=0.23, p <.05). Children with C-mTBI and mTBI-SF resume similar sports as children with mTBI. Those with C-mTBI and those who take longer to return to play may have lower risk of repeat mTBIs. Prospective research is needed to inform the development of evidence-based guidelines for children with C-mTBI and mTBI-SF.

Evidence for the Validation of a Single Item Recovery Question (SIRQ) in Children With Mild and Complicated Mild Traumatic Brain Injury

BackgroundRecovery from a brain injury occurs in varying degrees. The objective of this study was to investigate the concurrent validity of a parent-reported 10-point scale for degree of recovery, Single Item Recovery Question (SIRQ), in children with mild traumatic brain injury (mTBI) or complicated mTBI (C-mTBI) compared with validated assessments of symptom burden (Post-Concussion Symptom Inventory Parent form–PCSI-P) and quality of life (Pediatric Quality of Life Inventory [PedsQL]). MethodsA survey was sent to parents of children aged five to 18 years who presented to pediatric level I trauma center with mTBI or C-mTBI. Data included parent-reported postinjury recovery and functioning of children. Pearson correlation coefficients (r) were calculated to measure the associations of the SIRQ with the PCSI-P and the PedsQL. Hierarchical linear regression models were used to examine if covariates would increase the predictive value of the SIRQ to the PCSI-P and the PedsQL total scores. ResultsOf 285 responses (175 mTBI and 110 C-mTBI) analyzed, Pearson correlation coefficients for the SIRQ to the PCSI-P (r = −0.65, P < 0.001) and PedsQL total and subscale scores were all significant (P < 0.001) with mostly large-sized effects (r ≥ 0.500), regardless of mTBI classification. Covariates, including mTBI classification, age, gender, and years since injury, resulted in minimum changes in the predictive value of the SIRQ to the PCSI-P and the PedsQL total scores. ConclusionsThe findings demonstrate preliminary evidence for the concurrent validity of the SIRQ in pediatric mTBI and C-mTBI.

The Utah Pediatric Trauma Network, a statewide pediatric trauma collaborative can safely help nonpediatric hospitals admit children with mild traumatic brain injury.

Created in 2019, the Utah Pediatric Trauma Network (UPTN) is a transparent noncompetitive collaboration of all hospitals in Utah with the purpose of improving pediatric trauma care. The UPTN implements evidence-based guidelines based on hospital resources and capabilities with quarterly review of data collected in a network-specific database. The first initiative was to help triage the care of traumatic brain injury (TBI) to prevent unnecessary transfers while ensuring appropriate care. The purpose of this study was to review the effectiveness of this network wide guideline. The UPTN REDCap database was retrospectively reviewed between January 2019 and December 2021. Comparisons were made between the pediatric trauma center (PED1) and nonpediatric hospitals (non-PED1) in admissions of children with very mild, mild, or complicated mild TBI. Of the total 3,315 cases reviewed, 294 were admitted to a non-PED1 hospital and 1,061 to the PED1 hospital with very mild/mild/complicated mild TBI. Overall, kids treated at non-PED1 were older (mean, 14.9 vs. 7.7 years; p = 0.00001) and more likely to be 14 years or older (37% vs. 24%, p < 0.00001) compared with those at PED1. Increased admissions occurred post-UPTN at non-PED1 hospitals compared with pre-UPTN (43% vs. 14%, p < 0.00001). Children admitted to non-PED1 hospitals post-UPTN were younger (9.1 vs. 15.7 years, p = 0.002) with more kids younger than 14 years (67% vs. 38%, p = 0.014) compared with pre-UPTN. Two kids required next-day transfer to a higher-level center (1 to PED1), and none required surgery or neurosurgical evaluation. The mean length of stay was 21.8 hours (interquartile range, 11.9-25.4). Concomitantly, less children with very mild TBI were admitted to PED1 post-UPTN (6% vs. 27%, p < 0.00001) and more with complicated mild TBI (63% vs. 50%, p = 0.00003) than 2019. Implementation of TBI guidelines across the UPTN successfully allowed nonpediatric hospitals to safely admit children with very mild, mild, or complicated mild TBI. In addition, admitted kids were more like those treated at the PED1 hospital. Prognostic/Epidemiological; Level IV.

Longitudinal Abnormalities in White Matter Extracellular Free Water Volume Fraction and Neuropsychological Functioning in Patients with Traumatic Brain Injury.

Traumatic brain injury is a global public health problem associated with chronic neurological complications and long-term disability. Biomarkers that map onto the underlying brain pathology driving these complications are urgently needed to identify individuals at risk for poor recovery and to inform design of clinical trials of neuroprotective therapies. Neuroinflammation and neurodegeneration are two endophenotypes potentially associated with increases in brain extracellular water content, but the nature of extracellular free water abnormalities after neurotrauma and its relationship to measures typically thought to reflect traumatic axonal injury are not well characterized. The objective of this study was to describe the relationship between a neuroimaging biomarker of extracellular free water content and the clinical features of a cohort with primarily complicated mild traumatic brain injury. We analyzed a cohort of 59 adult patients requiring hospitalization for non-penetrating traumatic brain injury of all severities as well as 36 healthy controls. Patients underwent brain magnetic resonance imaging (MRI) at 2 weeks (n = 59) and 6 months (n = 29) post-injury, and controls underwent a single MRI. Of the participants with TBI, 50 underwent clinical neuropsychological assessment at 2 weeks and 28 at 6 months. For each subject, we derived a summary score representing deviations in whole brain white matter extracellular free water volume fraction (VF) and free water-corrected fractional anisotropy (fw-FA). The summary specific anomaly score (SAS) for VF was significantly higher in TBI patients at 2 weeks and 6 months post-injury relative to controls. SAS for VF exhibited moderate correlation with neuropsychological functioning, particularly on measures of executive function. These findings indicate abnormalities in whole brain white matter extracellular water fraction in patients with TBI and are an important step toward identifying and validating noninvasive biomarkers that map onto the pathology driving disability after TBI.

Inpatient management of complicated mTBI with the BIG assessment tool: Review and summary of the evidence

Introduction The management of mild traumatic brain injury has evolved through the years with an emphasis on the safe discharge of patients given current resources. In this article, we discuss key studies published in the past 12 years that have influenced the direction of complicated mild traumatic brain injury (cmTBI) management. We summarize the evidence on the utilization of the Brain Injury Guideline (BIG) algorithm. Methods An independent literature search was conducted on the BIG, updated versions of BIG, and the prognostic studies of adult mild traumatic brain injury admissions cited by the BIG articles. Evidence resources included the search engines of PubMed, Medline, Ovid, Cochrane Library, and Google Scholar bibliographic databases of items published between 1 January 2010 and 30 December 2021. The evidence focused on BIG and its modified versions, as a potential risk assessment tool for discharging mTBI patients early. Results Studies supporting the BIG algorithm prior to 2019 presented evidence with serious limitations to their findings. These limitations threaten their veracity and fail to support the efficacy or validation of the BIG algorithm's utilization for mTBI patient management. Conclusion The lack of rigor in the BIG algorithm studies suggest the research is currently insufficient to support early discharge and research needs to continue on modified versions of the tool before its widespread use.

Diffusion Tensor and Kurtosis Imaging Findings the First Year following Mild Traumatic Brain Injury.

Despite enormous research interest in diffusion tensor imaging and diffusion kurtosis imaging (DTI; DKI) following mild traumatic brain injury (MTBI), it remains unknown how diffusion in white matter evolves post-injury and relates to acute MTBI characteristics. This prospective cohort study aimed to characterize diffusion changes in white matter the first year after MTBI. Patients with MTBI (n = 193) and matched controls (n = 83) underwent 3T magnetic resonance imaging (MRI) within 72 h and 3- and 12-months post-injury. Diffusion data were analyzed in three steps: 1) voxel-wise comparisons between the MTBI and control group were performed with tract-based spatial statistics at each time-point; 2) clusters of significant voxels identified in step 1 above were evaluated longitudinally with mixed-effect models; 3) the MTBI group was divided into: (A) complicated (with macrostructural findings on MRI) and uncomplicated MTBI; (B) long (1-24 h) and short (< 1 h) post-traumatic amnesia (PTA); and (C) other and no other concurrent injuries to investigate if findings in step 1 were driven mainly by aberrant diffusion in patients with a more severe injury. At 72 h, voxel-wise comparisons revealed significantly lower fractional anisotropy (FA) in one tract and significantly lower mean kurtosis (Kmean) in 11 tracts in the MTBI compared with control group. At 3 months, the MTBI group had significantly higher mean diffusivity in eight tracts compared with controls. At 12 months, FA was significantly lower in four tracts and Kmean in 10 tracts in patients with MTBI compared with controls. There was considerable overlap in affected tracts across time, including the corpus callosum, corona radiata, internal and external capsule, and cerebellar peduncles. Longitudinal analyses revealed that the diffusion metrics remained relatively stable throughout the first year after MTBI. The significant group*time interactions identified were driven by changes in the control rather than the MTBI group. Further, differences identified in step 1 did not result from greater diffusion abnormalities in patients with complicated MTBI, long PTA, or other concurrent injuries, as standardized mean differences in diffusion metrics between the groups were small (0.07 ± 0.11) and non-significant. However, follow-up voxel-wise analyses revealed that other concurrent injuries had effects on diffusion metrics, but predominantly in other metrics and at other time-points than the effects observed in the MTBI versus control group analysis. In conclusion, patients with MTBI differed from controls in white matter integrity already 72 h after injury. Diffusion metrics remained relatively stable throughout the first year after MTBI and were not driven by deviating diffusion in patients with a more severe MTBI.