Determining the Minimally Clinically Important Difference for the Disability Rating Scale in Persons With Chronic Traumatic Brain Injury.

The Extended Glasgow Outcome Scale (GOSE) is accepted as the primary outcome measure in registrational studies for traumatic brain injury (TBI). The Disability Rating Scale (DRS) is used to assess functional progress from initial acute injury, through rehabilitation and reintegration into the community and life. For these reasons, the DRS is an alternative measure for assessing meaningful global outcomes in chronic TBI. The objective of this study was to determine the minimally clinically important difference (MCID) for the DRS in chronic TBI, by determining the magnitude of DRS change associated with the MCID for the GOSE of 1 point. This study is a retrospective analysis of the multi-center, prospective, longitudinal, Traumatic Brain Injury Model Systems National Database of persons with outcomes at 1, 2, and 5 years and every 5 years thereafter post-injury. Spearman's correlations for dynamic and static relationships between the DRS and GOSE were significant. For the 1-point MCID for the GOSE, the dynamic MCID estimate for the DRS of a -0.68-point change was calculated as the mean DRS change associated with the difference of the GOSE score between year 1 and year 2 (score range, 3-8), using all persons in the study (n = 11,102), whereas the exploratory static MCID estimate for the DRS of -1.28 points was calculated from the slope of the best-fit line between the DRS and GOSE at year 1 follow-up (score range, 3-8; n = 13,415). The final MCID for the DRS was calculated by using the triangulation method (i.e., the arithmetic mean of the dynamic and exploratory static MCID estimates), which resulted in a -1.0-point change. The significant correlation between the DRS and GOSE has allowed for the establishment of a -1.0-point MCID for the DRS, which supports the use of the DRS as an alternative primary outcome measure for chronic TBI research studies, including clinical trials.

Societal Participation of People With Traumatic Brain Injury Before and During the COVID-19 Pandemic: A NIDILRR Traumatic Brain Injury Model Systems Study.

OBJECTIVE: To examine the effect of the COVID-19 pandemic on societal participation in people with moderate-to-severe traumatic brain injury (TBI). DESIGN: Cross-sectional retrospective cohort. SETTING: National TBI Model Systems centers, United States. PARTICIPANTS: TBI Model Systems enrollees (N=7003), ages 16 and older and 1-30 years postinjury, interviewed either prepandemic (PP) or during the pandemic (DP). The sample was primarily male (72.4%) and White (69.5%), with motor vehicle collisions as the most common cause of injury (55.1%). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The 3 subscales of the Participation Assessment with Recombined Tools-Objective: Out and About (community involvement), Productivity, and Social Relations. RESULTS: Out and About, but not Productivity or Social Relations, scores were appreciably lower among DP participants compared to PP participants (medium effect). Demographic and clinical characteristics showed similar patterns of association with participation domains across PP and DP. When their unique contributions were examined in regression models, age, self-identified race, education level, employment status, marital status, income level, disability severity, and life satisfaction were variably predictive of participation domains, though most effects were small or medium in size. Depression and anxiety symptom severities each showed small zero-order correlations with participation domains across PP and DP but had negligible effects in regression analyses. CONCLUSIONS: Consistent with the effect of COVID-19 on participation levels in the general population, people with TBI reported less community involvement during the pandemic, potentially compounding existing postinjury challenges to societal integration. The pandemic does not appear to have altered patterns of association between demographic/clinical characteristics and participation. Assessing and addressing barriers to community involvement should be a priority for TBI treatment providers. Longitudinal studies of TBI that consider pandemic-related effects on participation and other societally linked outcomes will help to elucidate the potential longer-term effect the pandemic has on behavioral health in this population.

Depression, Anxiety, and Suicidality in Individuals With Chronic Traumatic Brain Injury Before and During the COVID-19 Pandemic: A National Institute on Disability, Independent Living, and Rehabilitation Research Traumatic Brain Injury Model Systems Study.

OBJECTIVE: To examine the prevalence, severity, and correlates of depression, anxiety, and suicidal ideation in people with traumatic brain injury (TBI) assessed before and during the COVID-19 pandemic. DESIGN: Retrospective cohort study using data collected through the Traumatic Brain Injury Model Systems (TBIMS) network at 1, 2, 5, 10, 15, 20, 25, or 30 years post TBI. SETTING: United States-based TBIMS rehabilitation centers with telephone assessment of community residing participants. PARTICIPANTS: Adults (72.4% male; mean age, 47.2 years) who enrolled in the TBIMS National Database and completed mental health questionnaires prepandemic (January 1, 2017 to February 29, 2020; n=5000) or during pandemic (April 1, 2022 to June 30, 2021; n=2009) (N=7009). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 questionnaire. RESULTS: Separate linear and logistic regressions were constructed with demographic, psychosocial, injury-related, and functional characteristics, along with a binary indicator of COVID-19 pandemic period (prepandemic vs during pandemic), as predictors of mental health outcomes. No meaningful differences in depression, anxiety, or suicidal ideation were observed before vs during the COVID-19 pandemic. Correlations between predictors and mental health outcomes were similar before and during the pandemic. CONCLUSIONS: Contrary to our predictions, the prevalence, severity, and correlates of mental health conditions were similar before and during the COVID-19 pandemic. Results may reflect generalized resilience and are consistent with the most recent findings from the general population that indicate only small, transient increases in psychological distress associated with the pandemic. While unworsened, depression, anxiety, and suicidal ideation remain prevalent and merit focused treatment and research efforts.

Recovery of Consciousness and Functional Outcome in Moderate and Severe Traumatic Brain Injury.

Importance: Traumatic brain injury (TBI) leads to 2.9 million visits to US emergency departments annually and frequently involves a disorder of consciousness (DOC). Early treatment, including withdrawal of life-sustaining therapies and rehabilitation, is often predicated on the assumed worse outcome of disrupted consciousness. Objective: To quantify the loss of consciousness, factors associated with recovery, and return to functional independence in a 31-year sample of patients with moderate or severe brain trauma. Design, Setting, and Participants: This cohort study analyzed patients with TBI who were enrolled in the Traumatic Brain Injury Model Systems National Database, a prospective, multiyear, longitudinal database. Patients were survivors of moderate or severe TBI who were discharged from acute hospitalization and admitted to inpatient rehabilitation from January 4, 1989, to June 19, 2019, at 1 of 23 inpatient rehabilitation centers that participated in the Traumatic Brain Injury Model Systems program. Follow-up for the study was through completion of inpatient rehabilitation. Exposures: Traumatic brain injury. Main Outcomes and Measures: Outcome measures were Glasgow Coma Scale in the emergency department, Disability Rating Scale, posttraumatic amnesia, and Functional Independence Measure. Patient-related data included demographic characteristics, injury cause, and brain computed tomography findings. Results: The 17 470 patients with TBI analyzed in this study had a median (interquartile range [IQR]) age at injury of 39 (25-56) years and included 12 854 male individuals (74%). Of these patients, 7547 (57%) experienced initial loss of consciousness, which persisted to rehabilitation in 2058 patients (12%). Those with persisting DOC were younger; had more high-velocity injuries; had intracranial mass effect, intraventricular hemorrhage, and subcortical contusion; and had longer acute care than patients without DOC. Eighty-two percent (n = 1674) of comatose patients recovered consciousness during inpatient rehabilitation. In a multivariable analysis, the factors associated with consciousness recovery were absence of intraventricular hemorrhage (adjusted odds ratio [OR], 0.678; 95% CI, 0.532-0.863; P = .002) and intracranial mass effect (adjusted OR, 0.759; 95% CI, 0.595-0.968; P = .03). Functional improvement (change in total functional independence score from admission to discharge) was +43 for patients with DOC and +37 for those without DOC (P = .002), and 803 of 2013 patients with DOC (40%) became partially or fully independent. Younger age, male sex, and absence of intraventricular hemorrhage, intracranial mass effect, and subcortical contusion were associated with better functional outcome. Findings were consistent across the 3 decades of the database. Conclusions and Relevance: This study found that DOC occurred initially in most patients with TBI and persisted in some patients after rehabilitation, but most patients with persisting DOC recovered consciousness during rehabilitation. This recovery trajectory may inform acute and rehabilitation treatment decisions and suggests caution is warranted in consideration of withdrawing or withholding care in patients with TBI and DOC.

Cell Therapy for Chronic TBI: Interim Analysis of the Randomized Controlled STEMTRA Trial.

OBJECTIVE: To determine if chronic motor deficits secondary to traumatic brain injury (TBI) can be improved by implantation of allogeneic modified bone marrow-derived mesenchymal stromal/stem cells (SB623). METHODS: This 6-month interim analysis of the 1-year double-blind, randomized, surgical sham-controlled, phase 2 STEMTRA trial (NCT02416492) evaluated safety and efficacy of the stereotactic intracranial implantation of SB623 in patients with stable chronic motor deficits secondary to TBI. Patients in this multi-center trial (N = 63) underwent randomization in a 1:1:1:1 ratio to 2.5 × 106, 5.0 × 106, 10 × 106 SB623 cells or control. Safety was assessed in patients who underwent surgery (N = 61), and efficacy in the modified intent-to-treat population of randomized patients who underwent surgery (N = 61; SB623 = 46, control = 15). RESULTS: The primary efficacy endpoint of significant improvement from baseline of Fugl-Meyer Motor Scale score at 6 months for SB623-treated patients was achieved. SB623-treated patients improved by (LS mean [SE]) +8.3 (1.4) vs +2.3 (2.5) for control at 6 months, the LS mean difference was 6.0 (95% CI: 0.3-11.8); p = 0.040. Secondary efficacy endpoints improved from baseline, but were not statistically significant vs control at 6 months. There were no dose-limiting toxicities or deaths, and 100% of SB623-treated patients experienced treatment-emergent adverse events vs 93.3% of control patients (p = 0.25). CONCLUSIONS: SB623 cell implantation appeared to be safe and well tolerated, and patients implanted with SB623 experienced significant improvement from baseline motor status at 6 months compared to controls. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that implantation of SB623 was well tolerated and associated with improvement in motor status.

Developing an Index of Medical Conditions Associated with Outcomes after Moderate-to-Severe Traumatic Brain Injury.

Medical conditions co-occurring with traumatic brain injury (TBI) are associated with outcomes, and comorbidity indices such as Charlson and Elixhauser are used in TBI research, but they are not TBI specific. The purpose of this research was to develop an index or indices of medical conditions, identified in acute care after moderate to severe TBI, that are associated with outcomes at rehabilitation discharge. Using the TBI Model Systems National Database, the International Classification of Diseases, Ninth Revision (ICD-9) and Tenth Revision (ICD-10) codes of 8988 participants were converted to Healthcare Cost and Utilization Project (HCUP) diagnostic categories. Poisson regression models were built predicting Disability Rating Scale and Functional Independence Measure Cognitive and Motor subscale scores from HCUP categories after controlling for demographic and injury characteristics. Unweighted, weighted, and anchored indices based on the outcome models predicted 7.5-14.3% of the variance in the observed outcomes. When the indices were applied to a new validation sample of 1613 cases, however, only 2.6-6.6% of the observed outcomes were predicted. Therefore, no models or indices were recommended for future use, but several study findings are highlighted suggesting the importance and the potential for future research in this area.

Testosterone replacement in hypogonadal men during inpatient rehabilitation following traumatic brain injury: Results from a double-blind, placebo-controlled clinical pilot study.

BACKGROUND: Endocrinopathy, including hypogonadism, is common following traumatic brain injury (TBI). Prior evidence suggests hypogonadism is associated with poorer function. OBJECTIVE: Determine the feasibility, safety, and efficacy of testosterone (T) therapy in hypogonadal men following TBI in acute rehabilitation. DESIGN: Randomized, double blind, placebo-controlled pilot trial. SETTING: Inpatient rehabilitation brain injury unit. PARTICIPANTS: Men ages 18 -65, post moderate to severe TBI receiving inpatient rehabilitation. INTERVENTIONS: Transdermal T gel or placebo. MAIN OUTCOME MEASURES: Revised FIM™ score, strength, adverse events. RESULTS: Of 498 screened, 70 participants were enrolled, and 22 meeting all criteria were randomized into placebo (n = 10) or physiologic T therapy (n = 12). There was no significant difference between groups in rate of improvement on the FIM™ (intercepts t = -0.31, p = 0.7593, or slopes t = 0.61, p = 0.5472). The Treatment group demonstrated the greatest absolute improvement in FIM™ scores and grip strength compared to Placebo or Normal T groups. There was no difference in adverse events between groups. Percentage of time with agitation or aggression was highest in the Placebo group. CONCLUSIONS: Although there were no significant differences in rates of recovery, treatment group subjects showed greater absolute functional and strength improvement compared to the Placebo or Normal T groups.

Impact of timing of ventriculoperitoneal shunt placement on outcome in posttraumatic hydrocephalus.

OBJECTIVE Posttraumatic hydrocephalus (PTH) is a frequent sequela of traumatic brain injury (TBI) and complication of related cranial surgery. The roles of PTH and the timing of cerebrospinal fluid (CSF) shunt placement in TBI outcome have not been well described. The goal of this study was to assess the impact of hydrocephalus and timing of ventriculoperitoneal (VP) shunt placement on outcome during inpatient rehabilitation after TBI. METHODS In this cohort study, all TBI patients admitted to Craig Hospital between 2009 and 2013 were evaluated for PTH, defined as ventriculomegaly, and hydrocephalus symptoms, delayed or deteriorating recovery, or elevated opening pressure on lumbar puncture. Extent of ventriculomegaly was quantified by the Evans index from CT scans. Outcome measures were emergence from and duration of posttraumatic amnesia (PTA) and functional status as assessed by means of the Functional Independence Measure (FIM). Findings in this group were compared to findings in a group of TBI patients without PTH (controls) who were admitted for inpatient rehabilitation during the same study period and met specific criteria for inclusion. RESULTS A total of 701 patients were admitted with TBI during the study period. Of these patients, 59 (8%) were diagnosed with PTH and were included in this study as the PTH group, and 204 who were admitted for rehabilitation and met the criteria for inclusion as controls constituted the comparison group (no-PTH group). PTH was associated with initial postinjury failure to follow commands, midline shift or cistern compression, subcortical contusion, and craniotomy or craniectomy. In multivariable analyses, independent predictors of longer PTA duration and lower FIM score at rehabilitation discharge were PTH, emergency department Glasgow Coma Scale motor score < 6, and longer time from injury to rehabilitation admission. PTH accounted for a 51-day increase in PTA duration and a 29-point reduction in discharge FIM score. In 40% of PTH patients with preshunt CT brain imaging analyzed, ventriculomegaly (Evans index > 0.3) was observed 3 or more days before VP shunt placement (median 10 days, range 3-102 days). Among PTH patients who received a VP shunt, earlier placement was associated with better outcome by all measures assessed and independently predicted better FIM total score and shorter PTA duration. CONCLUSIONS Posttraumatic hydrocephalus predicts worse outcome during inpatient rehabilitation, with poorer functional outcomes and longer duration of PTA. In shunt-treated PTH patients, earlier CSF shunting predicted improved recovery. These results suggest that clinical vigilance for PTH onset and additional studies on timing of CSF diversion are warranted.

Posttraumatic Hydrocephalus as a Confounding Influence on Brain Injury Rehabilitation: Incidence, Clinical Characteristics, and Outcomes.

OBJECTIVE: To describe incidence, clinical characteristics, complications, and outcomes in posttraumatic hydrocephalus (PTH) after traumatic brain injury (TBI) for patients treated in an inpatient rehabilitation program. DESIGN: Cohort study with retrospective comparative analysis. SETTING: Inpatient rehabilitation hospital. PARTICIPANTS: All patients admitted for TBI from 2009 to 2013 diagnosed with PTH (N=59), defined as ventriculomegaly, delayed clinical recovery discordant with injury severity, hydrocephalus symptoms, or positive lumbar puncture results. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Primary measures were incidence of PTH and patient and injury characteristics. Secondary measures included frequency and timing of ventriculoperitoneal (VP) shunt, related complications, emergence from and duration of posttraumatic amnesia (PTA), Rancho Los Amigos Scale (RLAS) score, and FIM score at rehabilitation admission and discharge. RESULTS: Of 701 patients with TBI admitted, 59 (8%) were diagnosed with PTH. Of these, the median age was 25 years, with 73% being men. At initial presentation, 52 (88%) did not follow commands. Fifty-two (90%) patients with PTH had a VP shunt placed. Median time from injury to shunt placement was 69 (range, 9-366) days. Seven (12%) patients with PTH experienced postsurgical seizure, 3 (6%) had shunt infection, and 7 (12%) had shunt malfunction. Thirty-six (61%) patients with PTH emerged from PTA during rehabilitation. Median total FIM score at rehabilitation admission was 20 (range, 18-76), and at discharge it was 43 (range, 18-118). Injury severity predicted outcome at rehabilitation admission, whereas shunt timing predicted outcome at rehabilitation discharge. CONCLUSIONS: Incidence of PTH was observed in 8% of patients with TBI in inpatient rehabilitation. Earlier shunting predicted improved outcome during rehabilitation. Future studies should prospectively examine clinical decision rules, type, and timing of intervention and the coeffectiveness of rehabilitation treatment on outcomes.

Magnetic resonance imaging of traumatic brain injury: relationship of T2*SE and T2GE to clinical severity and outcome.

PRIMARY OBJECTIVES: To evaluate (1) the sensitivity of magnetic resonance imaging (MRI) T2* weighted gradient echo (GE) vs T2 weighted spin echo (SE) technology for lesion detection in traumatic brain injury (TBI) and (2) the relationship of lesion patterns to acute clinical severity and 1 year post-injury outcome measures. RESEARCH DESIGN: Comparative analysis. METHODS AND PROCEDURES: Forty-three acute rehabilitation patients with TBI were imaged utilizing T2 SE and T2* GE techniques an average of 26 days post-injury. Acute clinical severity measures, including Glasgow Coma Scale (GCS), time to follow commands (TFC) and post-traumatic amnesia (PTA) were abstracted from medical records. One-year post-injury outcome measures including Glasgow Outcome Scale (GOS), Disability Rating Scale (DRS) and the Craig Handicap Assessment and Reporting Technique--Short Form (CHART-SF) were collected as part of a comprehensive annual follow-up. MAIN OUTCOMES AND RESULTS: In comparison to T2 SE, T2* GE more frequently detected lesions in each of the cortical (p <0.0001), white matter (p <0.001), central grey (p <0.001) and brainstem (p <0.01) regions and in each of the frontal (p <0.0001), temporal (p <0.0001), parietal (p <0.001) and occipital (p <0.0001) lobes. With regards to acute clinical severity measures, T2* GE findings were the best predictors of GCS and the only significant predictors of PTA, while T2 SE findings were better predictors of TFC. For 1 year post-injury outcome measures, multivariate regression models utilizing T2 SE and T2* GE findings in combination were the best predictors of DRS and GOS and T2 SE findings alone were the best predictors of CHART-SF. CONCLUSIONS: This study demonstrates the enhanced sensitivity of T2* GE for detecting haemorrhagic lesions associated with TBI and supports a complimentary role for both T2 SE and T2* GE weighted imaging in characterizing injury severity and predicting longer-term outcomes.

Violence-related traumatic brain injury: a population-based study.

BACKGROUND: Most studies of traumatic brain injury (TBI) and violence are small, focus on one violent mechanism only, and are nonrepresentative. This large, population-based effort examines characteristics, circumstances of injury, treatment pathways, and outcomes of persons with TBI as a result of all types of violence, compares them with other TBI survivors, identifies a risk profile, and examines how a violent cause impacts later outcomes. METHODS: This study involved medical record abstraction and telephone survey at 1 year postinjury of a weighted sample of 2,771 Coloradans hospitalized with TBI between January 1, 1996, and June 30, 1999. RESULTS: People with violently incurred TBI are more likely to be young, male, members of minority groups, single, and premorbid alcohol abusers than other TBI survivors. At 1 year postinjury, they report less community integration and more headaches, confusion, and sensory and attentional disturbances. Predictors of these outcomes included age, gender, injury severity, and employment status. CONCLUSION: It appears that essentially the same factors that increase risk of sustaining a violent TBI negatively impact later outcomes as well.