Moderate-severe Traumatic Brain Injury Research Articles

Intracranial Pressure-Derived Cerebrovascular Reactivity Indices and Their Critical Thresholds: A Canadian High Resolution-Traumatic Brain Injury Validation Study.

Current neurointensive care guidelines recommend intracranial pressure (ICP) and cerebral perfusion pressure (CPP) centered management for moderate-severe traumatic brain injury (TBI) because of their demonstrated associations with patient outcome. Cerebrovascular reactivity metrics, such as the pressure reactivity index (PRx), pulse amplitude index (PAx), and RAC index, have also demonstrated significant prognostic capabilities with regard to outcome. However, critical thresholds for cerebrovascular reactivity indices have only been identified in two studies conducted at the same center. In this study, we aim to determine the critical thresholds of these metrics by leveraging a unique multi-center database. The study included a total of 354 patients from the CAnadian High-Resolution TBI (CAHR-TBI) Research Collaborative. Based on 6-month Glasgow Outcome Scores, patients were dichotomized into alive versus dead and favorable versus unfavorable. Chi-square values were then computed for incrementally increasing values of each physiological parameter of interest against outcome. The values that generated the greatest chi-squares for each parameter were considered to be the thresholds with the greatest outcome discriminatory capacity. To confirm that the identified thresholds provide prognostic utility, univariate and multivariable logistical regression analyses were performed adjusting for the International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) variables. Through the chi-square analysis, a lower limit CPP threshold of 60 mm Hg and ICP thresholds of 18 mm Hg and 22 mm Hg were identified for both survival and favorable outcome predictions. For the cerebrovascular reactivity metrics, different thresholds were identified for the two outcome dichotomizations. For survival prediction, thresholds of 0.35, 0.25, and 0 were identified for PRx, PAx, and RAC, respectively. For favorable outcome prediction, thresholds of 0.325, 0.20, and 0.05 were found. Univariate logistical regression analysis demonstrated that the time spent above/below thresholds were associated with outcome. Further, multivariable logistical regression analysis found that percent time above/below the identified thresholds added additional variance to the IMPACT core model for predicting both survival and favorable outcome. In this study, we were able to validate the results of the previous two works as well as to reaffirm the ICP and CPP guidelines from the Brain Trauma Foundation (BTF) and the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC).

Association of Early Dexmedetomidine Utilization With Clinical and Functional Outcomes Following Moderate-Severe Traumatic Brain Injury: A Transforming Clinical Research and Knowledge in Traumatic Brain Injury Study.

To examine early sedation patterns, as well as the association of dexmedetomidine exposure, with clinical and functional outcomes among mechanically ventilated patients with moderate-severe traumatic brain injury (msTBI). Retrospective cohort study with prospectively collected data. Eighteen Level-1 Trauma Centers, United States. Adult (age > 17) patients with msTBI (as defined by Glasgow Coma Scale < 13) who required mechanical ventilation from the Transforming Clinical Research and Knowledge in TBI (TRACK-TBI) study. None. Using propensity-weighted models, we examined the association of early dexmedetomidine exposure (within the first 5 d of ICU admission) with the primary outcome of 6-month Glasgow Outcomes Scale Extended (GOS-E) and the following secondary outcomes: length of hospital stay, hospital mortality, 6-month Disability Rating Scale (DRS), and 6-month mortality. The study population included 352 subjects who required mechanical ventilation within 24 hours of admission. The initial sedative medication was propofol for 240 patients (68%), midazolam for 59 patients (17%), ketamine for 6 patients (2%), dexmedetomidine for 3 patients (1%), and 43 patients (12%) never received continuous sedation. Early dexmedetomidine was administered in 77 of the patients (22%), usually as a second-line agent. Compared with unexposed patients, early dexmedetomidine exposure was not associated with better 6-month GOS-E (weighted odds ratio [OR] = 1.48; 95% CI, 0.98-2.25). Early dexmedetomidine exposure was associated with lower DRS (weighted OR = -3.04; 95% CI, -5.88 to -0.21). In patients requiring ICP monitoring within the first 24 hours of admission, early dexmedetomidine exposure was associated with higher 6-month GOS-E score (OR 2.17; 95% CI, 1.24-3.80), lower DRS score (adjusted mean difference, -5.81; 95% CI, -9.38 to 2.25), and reduced length of hospital stay (hazard ratio = 1.50; 95% CI, 1.02-2.20). Variation exists in early sedation choice among mechanically ventilated patients with msTBI. Early dexmedetomidine exposure was not associated with improved 6-month functional outcomes in the entire population, although may have clinical benefit in patients with indications for ICP monitoring.

Adaptation and Validation of the Standardized Swallowing Assessment Tool for Patients With Moderate-Severe Traumatic Brain Injury and Cervical Spinal Cord Injury.

Oropharyngeal dysphagia is common in moderate-severe traumatic brain injury (TBI) and cervical spinal cord injury (SCI) patients and can have serious consequences. Delaying feeding in these patients can also be detrimental. Nonetheless, the psychometric properties of screening tools that can promptly identify dysphagia have never been tested in these neurotrauma populations. This study aimed to: (1) adapt, translate, and validate the content of the French-Canadian version of the the Standardized Swallowing Assessment (SSA) tool to meet the needs of moderate-severe TBI and cervical SCI patients, (2) examine its inter-rater reliability and criterion-concurrent validation, and (3) evaluate its clinical utility from the perspectives of critical care nurses. The SSA tool was adapted and translated using an integrated method for the cultural adaptation and translation of tools. Eleven experts participated in the adaptation of the SSA tool, which led to the clarification of one item, as well as a new step and instructions for the screening procedure. Content validation (i.e., item and scale relevance) was evaluated by multidisciplinary team members (n = 17). The mean content validity index (CVI) score was 0.97 for the entire scale, while the mean CVI scores for individual items ranged from 0.82 to 1.0. A total of 60 neurotrauma patients were enrolled for inter-rater reliability and criterion-concurrent validation. Interrater reliability was determined by comparing two scores: one score from nurses responsible for the care of enrolled patients and one score from the research nurse. The weighted kappa coefficients for inter-rater reliability were 0.86 for moderate-severe TBI patients (n = 30) and 0.73 for cervical SCI patients (n = 30). A speech language therapist (SLT) also assessed dysphagia and results were used as the standard clinical reference criterion to determine concurrent validity (sensibility and specificity) of the adapted SSA tool. The sensitivity and specificity were 92% and 50% for moderate-severe TBI, and 77% and 75% for cervical SCI, respectively. The positive predictive value (PPV) and the negative predictive value (NPV) were 65% and 87% in TBI patients, and 75% and 76% in SCI patients. Test accuracy was 71% and 77% for these same groups. The clinical utility of the tool was evaluated according to the following domains: appropriateness, accessibility of the required material, applicability, perceived effectiveness, and acceptability. Acceptability was the only domain with a level of agreement <80% (74%) among trauma critical care nurses (n = 49). Findings support the content validation and inter-rater reliability of the adapted French-Canadian version of the SSA tool in moderate-severe TBI and cervical SCI patients. Sensitivity was acceptable in both groups, but the specificity was lower, especially in moderate-severe TBI patients. Further validation of the adapted French-Canadian version of the SSA tool is needed in neurotrauma patients to confirm these results and to ensure safe dysphagia screening while avoiding oral feeding deferrals.

Self-Reported Symptoms of Vertigo and Imbalance Are Prevalent Among Adults With Chronic Moderate-Severe Traumatic Brain Injury: A Preliminary Analysis.

Dizziness and imbalance are common symptoms during the acute phase of traumatic brain injury (TBI). However, there is evidence to suggest that these symptoms persist into the chronic phase of injury. Few prospective studies have examined the frequency and type of dizziness and imbalance in adults with chronic moderate-severe TBI. The aim of this preliminary analysis was to investigate the prevalence of these symptoms in adults with chronic moderate-severe TBI. Twenty-four adults with chronic moderate-severe TBI and a group of 19 age-, sex-, and education-matched noninjured comparison participants were recruited. Self-reported dizziness and imbalance were measured using a modified version of a standard case history form. Significant associations between group (TBI group or noninjured comparison [NC] participants) and self-reports of dizziness, imbalance, and related symptoms (endorsed "yes" or "no") were explored. The TBI group most reported lightheadedness (75%), vertigo (38%), and imbalance and/or falling (46%). The most common related symptom reported by the TBI group was headache (63%) and nausea (46%). Significant associations revealed that the TBI group responded "yes" in higher percentages than the NC group across all categories (dizziness, imbalance, and related symptoms). There were no statistically significant relationships among dizziness, imbalance, or headache symptoms within the TBI group. These preliminary findings suggest that dizziness and imbalance are prevalent in adults with chronic moderate-severe TBI. Persistent vertiginous symptoms may point to an underlying vestibular impairment. However, further research is needed to characterize vestibular function in chronic moderate-severe TBI.

Memory for social media images following traumatic brain injury

ABSTRACT Primary objective An emerging body of research examines the role of computer-mediated communication in supporting social connection in persons with traumatic brain injury (TBI). We examine the cognitive impacts of engaging with images posted to social media for persons with moderate-severe TBI. Research design Prior work shows that after viewing social media posts, adults have better memory for posts when they generate a comment about the post. We examined if persons with TBI experience a memory benefit for commented-upon social media images similar to non-injured comparison participants. Methods and procedures 53 persons with moderate-to-severe TBI and 52 non-injured comparison participants viewed arrays of real social media images and were prompted to comment on some of them. After a brief delay, a surprise two-alternative forced choice recognition memory test measured memory for these images. Main outcomes and results Persons with TBI remembered social media images at above-chance levels and experienced a commenting-related memory boost much like non-injured comparison participants. Conclusions These findings add to a growing literature on the potential benefits of social media use in individuals with TBI and point to the benefits of active engagement for memory in social media contexts in TBI.

Characterizing depression after traumatic brain injury using a symptom-oriented approach

BackgroundProgress in addressing depression after traumatic brain injury (TBI) has been limited. Traditional approaches to measuring depression classify individuals with diverse symptoms as having the same problem. We adopted a novel, symptom-oriented approach to characterize post-TBI depression, emphasizing specific symptoms rather than the number of symptoms. MethodsWe assessed depressive symptoms cross-sectionally in 393 participants with moderate-severe TBI (range 0.4–35.4 years post-injury; M = 12.6) using the Inventory of Depression and Anxiety Symptoms – Expanded Version (IDAS-II). We analyzed symptoms of DSM-5 major depressive disorder (MDD), separating compound symptoms into sub-symptoms. We quantified depression heterogeneity across 16 specific symptoms and explored associations between each symptom and personal, injury-related, treatment, and functional/psychosocial outcome factors. Results28 % of participants self-reported a current depression diagnosis, and 35 % met DSM-5 symptom criteria for MDD. Depressed participants (according to either self-reported diagnosis or MDD symptom criteria) were more likely to endorse each specific depressive symptom, including those that overlap with TBI. Post-TBI depression was highly heterogeneous, with 84–91 % of depressed participants (depending on classification method) showing a unique symptom profile not shared with any other individual. The most common symptom profile was shared by only three individuals. This heterogeneity was meaningful, as specific depressive symptoms had distinct associations with personal, injury-related, treatment, and outcome factors. LimitationsCross-sectional design. We only analyzed DSM-5 MDD symptoms, and some symptoms were assessed using only one item. ConclusionsA symptom-oriented approach to post-TBI depression captures the individual's unique profile of depressive symptoms, which relate differently to outcomes and other factors. We recommend future studies investigating post-TBI depression analyze specific symptoms alongside overall depression scores.

Fatigue, Executive Functioning, and Quality of Life: Exploring Relationships in Children With Traumatic Brain Injury.

The overall purpose of this study was to explore the relationship between fatigue, executive functioning, and quality of life for children with moderate-severe traumatic brain injury (TBI) between 8 and 17 years old. Fifteen parents of children with moderate-severe TBI (M = 10.06 years old) completed an online survey. Data from the following measures were included in this study's analyses: demographic and injury questions, the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2), Pediatric Quality of Life Inventory Generic Core Scale (PedsQL GCS)-parent report, and Pediatric Quality of Life Inventory Multidimensional Fatigue Scale (PedsQL MFS)-parent report. In a multiple regression, fatigue was found to be a significant predictor of quality of life for children with TBI, but executive functioning was not a significant predictor. When examining subdomains of functioning, worse sleep/rest fatigue and emotional executive functioning were most consistently associated with worse physical and psychosocial quality of life. The findings of this study suggest that fatigue could be an important contributing factor to reduced quality of life for children with moderate-severe TBI. Medical and educational professionals, including speech-language pathologists, should assess children with TBI for the presence and impact of fatigue. Further research is needed to understand how different subdomains of fatigue might interact with executive functioning to impact quality of life.

Outlier Analysis for Acute Blood Biomarkers of Moderate and Severe Traumatic Brain Injury.

Blood biomarkers have been studied to improve the clinical assessment and prognostication of patients with moderate-severe traumatic brain injury (mo/sTBI). To assess their clinical usability, one needs to know of potential factors that might cause outlier values and affect clinical decision making. In a prospective study, we recruited patients with mo/sTBI (n = 85) and measured the blood levels of eight protein brain pathophysiology biomarkers, including glial fibrillary acidic protein (GFAP), S100 calcium-binding protein B (S100B), neurofilament light (Nf-L), heart-type fatty acid-binding protein (H-FABP), interleukin-10 (IL-10), total tau (T-tau), amyloid β40 (Aβ40) and amyloid β42 (Aβ42), within 24 h of admission. Similar analyses were conducted for controls (n = 40) with an acute orthopedic injury without any head trauma. The patients with TBI were divided into subgroups of normal versus abnormal (n = 9/76) head computed tomography (CT) and favorable (Glasgow Outcome Scale Extended [GOSE] 5-8) versus unfavorable (GOSE <5) (n = 38/42, 5 missing) outcome. Outliers were sought individually from all subgroups from and the whole TBI patient population. Biomarker levels outside Q1 - 1.5 interquartile range (IQR) or Q3 + 1.5 IQR were considered as outliers. The medical records of each outlier patient were reviewed in a team meeting to determine possible reasons for outlier values. A total of 29 patients (34%) combined from all subgroups and 12 patients (30%) among the controls showed outlier values for one or more of the eight biomarkers. Nine patients with TBI and five control patients had outlier values in more than one biomarker (up to 4). All outlier values were > Q3 + 1.5 IQR. A logical explanation was found for almost all cases, except the amyloid proteins. Explanations for outlier values included extremely severe injury, especially for GFAP and S100B. In the case of H-FABP and IL-10, the explanation was extracranial injuries (thoracic injuries for H-FABP and multi-trauma for IL-10), in some cases these also were associated with abnormally high S100B. Timing of sampling and demographic factors such as age and pre-existing neurological conditions (especially for T-tau), explained some of the abnormally high values especially for Nf-L. Similar explanations also emerged in controls, where the outlier values were caused especially by pre-existing neurological diseases. To utilize blood-based biomarkers in clinical assessment of mo/sTBI, very severe or fatal TBIs, various extracranial injuries, timing of sampling, and demographic factors such as age and pre-existing systemic or neurological conditions must be taken into consideration. Very high levels seem to be often associated with poor prognosis and mortality (GFAP and S100B).

Regulation of microglial responses after pediatric traumatic brain injury: exploring the role of SHIP-1.

Severe traumatic brain injury (TBI) is the world's leading cause of permanent neurological disability in children. TBI-induced neurological deficits may be driven by neuroinflammation post-injury. Abnormal activity of SH2 domain-containing inositol 5' phosphatase-1 (SHIP-1) has been associated with dysregulated immunological responses, but the role of SHIP-1 in the brain remains unclear. The current study investigated the immunoregulatory role of SHIP-1 in a mouse model of moderate-severe pediatric TBI. SHIP-1+/- and SHIP-1-/- mice underwent experimental TBI or sham surgery at post-natal day 21. Brain gene expression was examined across a time course, and immunofluorescence staining was evaluated to determine cellular immune responses, alongside peripheral serum cytokine levels by immunoassays. Brain tissue volume loss was measured using volumetric analysis, and behavior changes both acutely and chronically post-injury. Acutely, inflammatory gene expression was elevated in the injured cortex alongside increased IBA-1 expression and altered microglial morphology; but to a similar extent in SHIP-1-/- mice and littermate SHIP-1+/- control mice. Similarly, the infiltration and activation of CD68-positive macrophages, and reactivity of GFAP-positive astrocytes, was increased after TBI but comparable between genotypes. TBI increased anxiety-like behavior acutely, whereas SHIP-1 deficiency alone reduced general locomotor activity. Chronically, at 12-weeks post-TBI, SHIP-1-/- mice exhibited reduced body weight and increased circulating cytokines. Pro-inflammatory gene expression in the injured hippocampus was also elevated in SHIP-1-/- mice; however, GFAP immunoreactivity at the injury site in TBI mice was lower. TBI induced a comparable loss of cortical and hippocampal tissue in both genotypes, while SHIP-1-/- mice showed reduced general activity and impaired working memory, independent of TBI. Together, evidence does not support SHIP-1 as an essential regulator of brain microglial morphology, brain immune responses, or the extent of tissue damage after moderate-severe pediatric TBI in mice. However, our data suggest that reduced SHIP-1 activity induces a greater inflammatory response in the hippocampus chronically post-TBI, warranting further investigation.

The Temporal Relationship Between Moderate to Vigorous Physical Activity and Secondary Conditions During the First Year After Moderate to Severe Traumatic Brain Injury

ObjectiveTo determine the cross-sectional and temporal relationships between minutes per week of moderate to vigorous physical activity (MVPA) as measured by a wrist-worn accelerometer and secondary conditions in the first year after moderate to severe traumatic brain injury (TBI). DesignProspective longitudinal cohort study. SettingFour inpatient rehabilitation centers. ParticipantsIndividuals (N = 180) with moderate-severe TBI enrolled in the TBI Model Systems Study. InterventionsParticipants wore a wrist accelerometer for 7 days immediately post discharge, and for 7 consecutive days at 6- and 12-months post injury. Main Outcome MeasuresMinutes per week of MVPA from daily averages based on wrist worn accelerometer. Secondary conditions included depression (Patient Health Questionnaire-9), fatigue (PROMIS Fatigue), Pain (Numeric Rating Scale), Sleep (Pittsburgh Sleep Quality Index), and cognition (Brief Test of Adult Cognition by Telephone). ResultsAt baseline, 6 and 12 months, 61%, 70% and 79% of the sample achieved at least 150 minutes per week of MVPA. The correlations between minutes of MVPA between baseline, 6 and 12 months were significant (r = 0.53-0.73), as were secondary conditions over these time points. However, no significant correlations were observed between minutes of MVPA and any secondary outcomes cross-sectionally or longitudinally at any time point. ConclusionsGiven the robust relationships physical activity has with outcomes in the general population, further research is needed to understand the effect of physical activity in individuals with moderate-severe TBI.

A - 141 Effects of Posttraumatic Growth on Current and Predicted Future Satisfaction with Recovery in Patients with Moderate/Severe Traumatic Brain Injury and their Families.

This study was designed to assess effects of posttraumatic growth (PTG) on ratings of current and predicted future functioning in adults with moderate-severe traumatic brain injury (mod-sev TBI) and their family members. Fifteen adults with mod-sev TBI (age 34.5; 4.1yrs post), and a family member for each, rated current, and predicted 2-3-year future, satisfaction with physical, cognitive, and emotional recovery. All participants also completed the Neurobehavioral Functioning Inventory, and patients completed the Motivation for TBI Rehabilitation Questionnaire. PTG was assessed by raters independently judging the content of brief narratives written by the patients. Results of repeated measures within-subjects contrasts and independent samples t-tests are reported at the p < 0.05 level. Findings for individuals with (vs without) PTG revealed greater agreement of current and future satisfaction by self and family member, including greater satisfaction with depression and aggression. Families rated less concern across areas of functioning, especially regarding aggression, for individuals with (vs without) PTG. Patients with (vs without) PTG rated poor current satisfaction with memory. Overall, patients with (vs without) PTG were less interested in rehabilitative treatment. Results align with published findings regarding PTG reflecting acceptance of personal challenges. Benefits to negative emotions are notable. Reasons for patients' current dissatisfaction with their memory, juxtaposed with satisfaction with their future memory, merits further study but may relate to patients' noticing memory difficulties while being evaluated. Less interest in rehab may relate to patients with PTG believing they were functioning well overall and therefore being less in need of treatment.

A - 150 Emotional Awareness in Individuals with Traumatic Brain Injury.

To examine emotional awareness in individuals with traumatic brain injury (TBI) utilizing the Levels of Emotional Awareness Scale (LEAS). Thirty-nine individuals with moderate-severe TBI received the Levels of Emotional Awareness Scale (LEAS) consisting of 10 scenarios. Each scenario contains two components: a self-component, where participants are required to describe how they would feel, and another component, where they describe how the other person in the scenario would feel. Individuals also received Empathy Scale (ES) and Empathy Quotient (EQ) to evaluate empathy as well as measures of quality of life (Quality of Life After Brain Injury QOLIBRI), satisfaction with life (SWL), and mood (Beck Depression Inventory-II BDI-II; State Trait Anxiety Inventory- STAI). Individuals with TBI had a mean age of 46.08 (12.67), education of 14.28 (1.90) years and were on the average 113.25 (104.63) months since injury. Results indicate that the LEAS is associated with empathy on both the ES r(39) =0.34, p = 0.034 and EQ r(39) =0.37, p = 0.019. The LEAS was not associated with QOLIBRI r(39) =0.09, p = 0.572, SWL r(39) = -0.18, p = 0.286, BDI-II r(39) =0.12, p = 0.453 or STAI r(39) =0.05, p = 0.758. Our data suggests individuals with TBI emotional awareness is associated with empathy, specifically lower emotional awareness is associated with lower empathy. Emotional awareness is not associated with quality of life, satisfaction with life or mood. Understanding the relationship between these two constructs may aide in where to target interventions to improve social outcomes for individuals with TBI.

Measurement of Sleep in Chronic Traumatic Brain Injury: Relationship Between Self-report and Actigraphy.

To examine the relationship between self-report and actigraphy measurement of sleep in people with and without traumatic brain injury (TBI) by addressing 2 aims: (1) to assess the relationship between self-report and actigraphy for sleep quantity in people with and without TBI; and (2) to explore how self-report and actigraphy capture sleep quality in TBI. Participants completed the study over 2 weeks in their own homes. They wore activity monitors, day and night, throughout the experiment and completed morning sleep diaries while interacting with an experimenter on videoconference. This project was embedded in a larger study on sleep and word learning in 100 adults: 50 with chronic, moderate-severe TBI and 50 demographically matched noninjured peers. Of the 100 participants who completed the larger study, 92 participants (45 with TBI and 47 noninjured peers) had sufficient actigraphy data for inclusion in the current study. We used multilevel linear regression models and correlation analyses to assess how well participants' self-report corresponded to actigraphy measurement of sleep. Actigraphy measures included nightly sleep duration and nighttime wakeups. Sleep diary measures included self-reported nightly sleep duration, nighttime wakeups, sleep quality, and morning fatigue. People with and without TBI did not differ in the relationship between self-reported and actigraphy measurement of sleep quantity. Performance on a neuropsychological memory assessment did not correlate with the difference in self-reported and actigraphy-measured sleep in the TBI group. Sleep characteristics that were measured by actigraphy did not predict subjective experiences of sleep quality or fatigue. Short-term self-report diaries capture accurate information about sleep quantity in individuals with TBI and may support self-report of other daily habits. Future research is needed to identify reliable metrics of sleep quality, and how they relate to other domains such as memory and mood, in the chronic phase of TBI.

Association of Early Beta-Blocker Exposure and Functional Outcomes in Critically Ill Patients With Moderate to Severe Traumatic Brain Injury: A Transforming Clinical Research and Knowledge in Traumatic Brain Injury Study.

We aimed to 1) describe patterns of beta-blocker utilization among critically ill patients following moderate-severe traumatic brain injury (TBI) and 2) examine the association of early beta-blocker exposure with functional and clinical outcomes following injury. Retrospective cohort study. ICUs at 18 level I, U.S. trauma centers in the Transforming Clinical Research and Knowledge in TBI (TRACK-TBI) study. Greater than or equal to 17 years enrolled in the TRACK-TBI study with moderate-severe TBI (Glasgow Coma Scale of <13) were admitted to the ICU after a blunt TBI. None. Primary exposure was a beta blocker during the first 7 days in the ICU, with a primary outcome of 6-month Glasgow Outcome Scale-Extended (GOSE). Secondary outcomes included: length of hospital stay, in-hospital mortality, 6-month and 12-month mortality, 12-month GOSE score, and 6-month and 12-month measures of disability, well-being, quality of life, and life satisfaction. Of the 450 eligible participants, 57 (13%) received early beta blockers (BB+ group). The BB+ group was on average older, more likely to be on a preinjury beta blocker, and more likely to have a history of hypertension. In the BB+ group, 34 participants (60%) received metoprolol only, 19 participants (33%) received propranolol only, 3 participants (5%) received both, and 1 participant (2%) received atenolol only. In multivariable regression, there was no difference in the odds of a higher GOSE score at 6 months between the BB+ group and BB- group (odds ratio = 0.86; 95% CI, 0.48-1.53). There was no association between BB exposure and secondary outcomes. About one-sixth of subjects in our study received early beta blockers, and within this group, dose, and timing of beta-blocker administration varied substantially. No significant differences in GOSE score at 6 months were demonstrated, although our ability to draw conclusions is limited by overall low total doses administered compared with prior studies.

Transdiagnostic MRI markers of psychopathology following traumatic brain injury: a systematic review and network meta-analysis protocol

IntroductionPsychopathology following traumatic brain injury (TBI) is a common and debilitating consequence that is often associated with reduced functional and psychosocial outcomes. There is a lack of evidence regarding the...

Serial Measurements of Serum Glial Fibrillary Acidic Protein in Moderate-Severe Traumatic Brain Injury: Potential Utility in Providing Insights into Secondary Insults and Long-Term Outcome.

In patients with traumatic brain injury (TBI), serum biomarkers may have utility in assessing the evolution of secondary brain injury. A panel of nine brain-injury- associated biomarkers was measured in archived serum samples over 10 days post-injury from 100 patients with moderate-severe TBI. Among the biomarkers evaluated, serum glial fibrillary acidic protein (GFAP) had the strongest associations with summary measures of acute pathophysiology, including intracranial pressure (ICP), cerebral perfusion pressure (CPP), and brain tissue pO2 (PbtO2). Group based trajectory (TRAJ) analysis was used to identify three distinct GFAP subgroups. The low TRAJ group (n = 23) had peak levels of 9.4 + 1.2 ng/mL that declined rapidly. The middle TRAJ group (n = 48) had higher peak values (31.5 + 5.0 ng/mL) and a slower decline over time. The high TRAJ group (n = 26) had very high, sustained peak values (59.6 + 12.5 ng/mL) that even rose among some patients over 10 days. Patients in the high TRAJ group had significantly higher mortality rate than patients in low and middle TRAJ groups (26.9% vs. 7.0%, p = 0.028). The frequency of poor neurological outcome (Glasgow Outcome Score Extended [GOS-E] 1-4) was 88.5% in the high TRAJ group, 54.2% in the middle TRAJ group, and 30.4% in the low TRAJ group (p < 0.001). ICP was highest in the high TRAJ group (median 17.6 mm Hg), compared with 14.4 mmHg in the low and 15.9 mm Hg in middle TRAJ groups (p = 0.002). High TRAJ patients spent the longest time with ICP >25 mm Hg, median 23 h, compared with 2 and 6 h in the low and middle TRAJ groups (p = 0.006), and the longest time with ICP >30 mm Hg, median 5 h, compared with 0 and 1 h in the low and middle TRAJ groups, respectively (p = 0.013). High TRAJ group patients more commonly required tier 2 or 3 treatment to control ICP. The high TRAJ group had the longest duration when CPP was <50 mm Hg (p = 0.007), and PbtO2 was <10 mm Hg (p = 0.002). Logistical regression was used to study the relationship between temporal serum GFAP patterns and 6-month GOS-E. Here, the low and middle TRAJ groups were combined to form a low-risk group, and the high TRAJ group was designated the high-risk group. High TRAJ group patients had a greater chance of a poor 6-month GOS-E (p < 0.0001). When adjusting for baseline injury characteristics, GFAP TRAJ group membership remained associated with GOS-E (p = 0.003). When an intensive care unit (ICU) injury burden score, developed to quantify physiological derangements, was added to the model, GFAP TRAJ group membership remained associated with GOS-E (p = 0.014). Mediation analysis suggested that ICU burden scores were in the causal pathway between TRAJ group and 6-month mortality or GOS-E. Our results suggest that GFAP may be useful to monitor serially in moderate-severe TBI patients. Future studies in larger cohorts are needed to confirm these results.

Intact speech-gesture integration in narrative recall by adults with moderate-severe traumatic brain injury

PurposeReal-world communication is situated in rich multimodal contexts, containing speech and gesture. Speakers often convey unique information in gesture that is not present in the speech signal (e.g., saying “He searched for a new recipe” while making a typing gesture). We examine the narrative retellings of participants with and without moderate-severe traumatic brain injury across three timepoints over two online Zoom sessions to investigate whether people with TBI can integrate information from co-occurring speech and gesture and if information from gesture persists across delays. Methods60 participants with TBI and 60 non-injured peers watched videos of a narrator telling four short stories. On key details, the narrator produced complementary gestures that conveyed unique information. Participants retold the stories at three timepoints: immediately after, 20-min later, and one-week later. We examined the words participants used when retelling these key details, coding them as a Speech Match (e.g., “He searched for a new recipe”), a Gesture Match (e.g., “He searched for a new recipe online), or Other (“He looked for a new recipe”). We also examined whether participants produced representative gestures themselves when retelling these details. ResultsDespite recalling fewer story details, participants with TBI were as likely as non-injured peers to report information from gesture in their narrative retellings. All participants were more likely to report information from gesture and produce representative gestures themselves one-week later compared to immediately after hearing the story. ConclusionWe demonstrated that speech-gesture integration is intact after TBI in narrative retellings. This finding has exciting implications for the utility of gesture to support comprehension and memory after TBI and expands our understanding of naturalistic multimodal language processing in this population.

Prognostic Value of Serum Biomarkers in Patients With Moderate-Severe Traumatic Brain Injury, Differentiated by Marshall Computer Tomography Classification.

Prognostication is challenging in patients with traumatic brain injury (TBI) in whom computed tomography (CT) fails to fully explain a low level of consciousness. Serum biomarkers reflect the extent of structural damage in a different way than CT does, but it is unclear whether biomarkers provide additional prognostic value across the range of CT abnormalities. This study aimed to determine the added predictive value of biomarkers, differentiated by imaging severity. This prognostic study used data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study (2014-2017). The analysis included patients aged ≥16 years with a moderate-severe TBI (Glasgow Coma Scale [GCS] <13) who had an acute CT and serum biomarkers obtained ≤24h of injury. Of six protein biomarkers (GFAP, NFL, NSE, S100B, Tau, UCH-L1), the most prognostic panel was selected using lasso regression. The performance of established prognostic models (CRASH and IMPACT) was assessed before and after the addition of the biomarker panel and compared between patients with different CT Marshall scores (Marshall score <3 vs. Marshall score ≥3). Outcome was assessed at six months post-injury using the extended Glasgow Outcome Scale (GOSE), and dichotomized into favorable and unfavorable (GOSE <5). We included 872 patients with moderate-severe TBI. The mean age was 47 years (range 16-95); 647 (74%) were male and 438 (50%) had a Marshall CT score <3. The serum biomarkers GFAP, NFL, S100B and UCH-L1 provided complementary prognostic information; NSE and Tau showed no added value. The addition of the biomarker panel to established prognostic models increased the area under the curve (AUC) by 0.08 and 0.03, and the explained variation in outcome by 13-14% and 7-8%, for patients with a Marshall score of <3 and ≥3, respectively. The incremental AUC of biomarkers for individual models was significantly greater when the Marshall score was <3 compared with ≥3 (p < 0.001). Serum biomarkers improve outcome prediction after moderate-severe TBI across the range of imaging severities and especially in patients with a Marshall score <3.

Critical Care Experience With Clinical Cerebral Autoregulation Testing in Adults With Traumatic Brain Injury.

To describe the setting, feasibility, and safety of static cerebral autoregulation testing in critically injured adults with traumatic brain injury (TBI). Methods: We reviewed static autoregulation testing using transcranial Doppler (TCD) ultrasound in patients > 18 years with TBI ICD codes between January 1, 2014, and December 31, 2021. Adverse events during testing were defined as systemic hypertension (systolic blood pressure (SBP>180 mmHg), bradycardia (HR<40 bpm), and high ICP (>30 mmHg). Impaired and absent cerebral autoregulation was defined as an autoregulatory index (ARI) <0.4 and ARI 0, respectively. We characterized prescribed changes in intracranial pressure (ICP) and cerebral perfusion pressure (CPP) targets by autoregulation testing results. Results: A total of 135 patients, median age 31 (interquartile range (IQR) 24, 43) years, 71.9% male, admission Glasgow coma scale (GCS) score 3 (IQR 3, 5.5), and 70.9% with subdural hematoma from severe (GCS 3-8; 133 (98.5%)) and moderate (GCS 9-12; 2 (1.5%)) TBI, underwent 309 attempted testing. All patients were mechanically ventilated and had ICP monitoring; 246 (80%) had brain tissue oxygen monitoring, and 68 (22%) had an external ventricular drain. The median number of autoregulation tests was two (range 1-3) tests/patient, and the median admission to the first test time was two days (IQR 1, 3). Of 55 (17.8%) tests not completed, systemic hypertension (32, 10.4%), intracranial hypertension (10, 3.2%), and bradycardia (3, 0.9%) were transient. Fifty-three (51%) of the first (n=104) autoregulation tests showed impaired/absent cerebral autoregulation. Impaired/absent autoregulation results at the first test were associated with repeat cerebral autoregulation testing (RR 2.25, 95% CI [1.40-3.60], p=0.0007) than intact cerebral autoregulation results. Pre-testing cerebral hemodynamic targets were maintained (n=131; 86.8%) when cerebral autoregulation was impaired (n=151; RR 1.49, 95% CI [1.25-1.77], p<0.0001). However, 15 (9.9%) test results led to higher ICP targets (from 20 mmHg to 25 mmHg), 5 (3.3%) results led to an increase in CPP target (from 60 mmHg to 70 mmHg), and five out of 131 (3.8%) patients underwent decompressive craniectomy and placement of an external ventricular drain. Intact cerebral autoregulation results (n=43/103, 41.7%) were associated with a change in ICP targets from 20 mmHg to 25 mmHg (RR 3.15, 95% CI [1.97-5.03], p<0.0001). Conclusions: Static cerebral autoregulation testing was feasible, safe, and useful in individualizing the care of patients with moderate-severe TBI receiving multimodal neuromonitoring. Testing results guided future testing, cerebral hemodynamic targets, and procedural decisions. Impaired cerebral autoregulation was very common.

Spatiotemporal profile of atrophy in the first year following moderate-severe traumatic brain injury.

Traumatic brain injury (TBI) triggers progressive neurodegeneration resulting in brain atrophy that continues months-to-years following injury. However, a comprehensive characterization of the spatial and temporal evolution of TBI-related brain atrophy remains incomplete. Utilizing a sensitive and unbiased morphometry analysis pipeline optimized for detecting longitudinal changes, we analyzed a sample consisting of 37 individuals with moderate-severe TBI who had primarily high-velocity and high-impact injury mechanisms. They were scanned up to three times during the first year after injury (3 months, 6 months, and 12 months post-injury) and compared with 33 demographically matched controls who were scanned once. Individuals with TBI already showed cortical thinning in frontal and temporal regions and reduced volume in the bilateral thalami at 3 months post-injury. Longitudinally, only a subset of cortical regions in the parietal and occipital lobes showed continued atrophy from 3 to 12 months post-injury. Additionally, cortical white matter volume and nearly all deep gray matter structures exhibited progressive atrophy over this period. Finally, we found that disproportionate atrophy of cortex along sulci relative to gyri, an emerging morphometric marker of chronic TBI, was present as early as 3 month post-injury. In parallel, neurocognitive functioning largely recovered during this period despite this pervasive atrophy. Our findings demonstrate msTBI results in characteristic progressive neurodegeneration patterns that are divergent across regions and scale with the severity of injury. Future clinical research using atrophy during the first year of TBI as a biomarker of neurodegeneration should consider the spatiotemporal profile of atrophy described in this study.