Phase 2 Randomized, Placebo-Controlled Clinical Trial of Recombinant Human Growth Hormone (rhGH) During Rehabilitation From Traumatic Brain Injury.

Traumatic brain injury (TBI) is a major cause of death and disability, but there are currently no therapies with proven efficacy for optimizing regeneration of repair during rehabilitation. Using standard stimulation tests, as many as 40-50% of survivors of severe TBI have deficiency of one or more pituitary hormones. Of these, the somatotropic axis is the most commonly affected, with Growth Hormone (GH) deficiency affecting ~20% of persons with severe TBI. Treatment with recombinant human Growth Hormone (rhGH) is generally effective in reversing the effects of acquired GH deficiency, but there is no evidence documenting functional or neurocognitive improvement after GH replacement in TBI patients. As a consequence, screening for GH deficiency and GH replacement when deficiency is found is not routinely performed as part of the rehabilitation of TBI survivors. Given that most of the recovery after TBI occurs within the first 6-12 months after injury and IGF-1 and GH are part of a coordinated restorative neurotrophic system, we hypothesized that patients will optimally benefit from GH therapy during the window of maximal neuroregenerative activity. We performed a Phase IIa, randomized, double-blind, placebo-controlled feasibility trial of recombinant human Growth Hormone (rhGH), starting at discharge from an inpatient rehabilitation unit, with follow up at 6 and 12 months. Our primary hypothesis was that treatment with rhGH in the subacute period would result in improved functional outcomes 6 months after injury. Our secondary hypothesis proposed that treatment with rhGH would increase IGF-1 levels and be well tolerated. Sixty-three subjects were randomized, and 40 completed the trial. At baseline, there was no correlation between IGF-1 levels and peak GH levels after L-arginine stimulation. IGF-1 levels increased after rhGH treatment, but it took longer than 1 month for levels to be higher than for placebo-treated patients. rhGH therapy was well-tolerated. The rhGH group was no different from placebo in the Disability Rating Scale, Glasgow Outcome Scale-Extended, or neuropsychological function. However, a trend toward greater improvement from baseline in Functional Independence Measure (FIM) was noted in the rhGH treated group. Future studies should include longer treatment periods, faster titration of rhGH, and larger sample sizes.

Promoting Bedside Nurse-Led Research Through a Dedicated Neuroscience Nursing Research Fellowship.

OBJECTIVE: We hypothesized that nurses would benefit from the fellowship model traditionally used to engage physicians in clinical research. The Neuroscience Nursing Research Center (NNRC) fellowship program was created as a model for engaging nurses at all levels of clinical practice to become active in clinical research. BACKGROUND: The NNRC was established in 2013 as a novel approach to promote bedside nurses as primary investigators in clinical research. METHODS: The NNRC developed 4 pathways to nursing research success: research fellowship, student-nurse internship, didactic training, and research consultation. RESULTS: Fellows have enrolled more than 900 participants in 14 studies. Nurses have presented more than 20 abstracts at 12 conferences and submitted 11 manuscripts for publication. The NNRC has provided research training to more than 150 nurses. CONCLUSIONS: The NNRC program is successful in engaging nurses in research. It shows promise to continue to develop nursing research that is applicable to clinicians and thus improve patient care.

Variations in Inpatient Rehabilitation Functional Outcomes Across Centers in the Traumatic Brain Injury Model Systems Study and the Influence of Demographics and Injury Severity on Patient Outcomes.

OBJECTIVE: To compare patient functional outcomes across Traumatic Brain Injury Model Systems (TBIMS) rehabilitation centers using an enhanced statistical model and to determine factors that influence those outcomes. DESIGN: Multicenter observational cohort study. SETTING: TBIMS centers. PARTICIPANTS: Patients with traumatic brain injury (TBI) admitted to 19 TBIMS rehabilitation centers from 2003-2012 (N=5505). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Functional outcomes of patients with TBI. RESULTS: Individuals with lower functional status at the time of admission, longer duration of posttraumatic amnesia, and higher burden of medical comorbidities continued to have worse functional outcomes at discharge from inpatient rehabilitation and at the 1-year follow-up, whereas those who were employed at the time of injury had better outcomes at both time periods. Risk-adjusted patient functional outcomes for patients in most TBIMS centers were consistent with previous research. However, there were wide performance differences for a few centers even after using more recently collected data, improving on the regression models by adding predictors known to influence functional outcomes, and using bootstrapping to eliminate confounds. CONCLUSIONS: Specific patient, injury, and clinical factors are associated with differences in functional outcomes within and across TBIMS rehabilitation centers. However, these factors did not explain all the variance in patient outcomes, suggesting a role of some other predictors that remain unknown.

Cytotoxic and vasogenic cerebral oedema in traumatic brain injury: assessment with FLAIR and DWI imaging.

PRIMARY OBJECTIVE: Cerebral oedema is a common complication of traumatic brain injury (TBI). The use of Fluid-Attenuated Inversion Recovery (FLAIR) imaging in combination with Diffusion Weighted Imaging (DWI) has the potential to distinguish between cytotoxic and vasogenic oedema. This study hypothesized a significant relationship between cytotoxic lesion volume and outcome. RESEARCH DESIGN: This observational study reports on a convenience sample where MRI was obtained for clinical purposes. METHODS AND PROCEDURES: Clinical post-TBI FLAIR and DWI images were analysed. For this study, lesions were defined as primarily cytotoxic oedema if the ratio of FLAIR to DWI lesion volume was comparable, defined as a ratio <2. If the ratio of FLAIR to DWI lesion volume was ≥2, oedema was considered predominantly of vasogenic origin. MAIN OUTCOMES AND RESULTS: The sample consisted primarily of males with TBIs whose injury severity ranged from complicated mild to severe. Analysis revealed that both oedema types are common after TBI and both are associated with functional deficits 6 months after injury. CONCLUSIONS: Acute MRI may be useful to assess pathology at the tissue after traumatic brain injury. Clinical trials targeting cytotoxic and vasogenic mechanisms of oedema formation may benefit from using DWI and FLAIR MRI as a means to differentiate the predominant oedema type after TBI.

Comparative effectiveness of traumatic brain injury rehabilitation: differential outcomes across TBI model systems centers.

OBJECTIVE: To measure patient functional outcomes across rehabilitation centers. SETTING: Traumatic Brain Injury Model System (TBIMS) centers. PARTICIPANTS: Patients with traumatic brain injury (TBI) admitted to 21 TBIMS rehabilitation centers (N = 6975, during 1999-2008). DESIGN: Retrospective analysis of prospectively collected data. MAIN MEASURES: Center-specific functional outcomes of TBI patients using Functional Independence Measure, Disability Rating Scale, and Glasgow Outcome Scale-Extended. RESULTS: There were large differences in patient characteristics across centers (demographics, TBI severity, and functional deficits at admission to rehabilitation). However, even after taking those factors into account, there were significant differences in functional outcomes of patients treated at different TBIMS centers. CONCLUSION: There are significant differences in functional outcomes of TBI patients across rehabilitation centers.

Effects of platelet and plasma transfusion on outcome in traumatic brain injury patients with moderate bleeding diatheses.

Object Coagulopathy and thrombocytopenia are common after traumatic brain injury (TBI), yet transfusion thresholds for mildly to moderately abnormal ranges of international normalized ratio and platelet count remain controversial. This study evaluates associations between fresh frozen plasma (FFP) and platelet transfusions with long-term functional outcome and survival in TBI patients with moderate hemostatic laboratory abnormalities. Methods This study is a retrospective review of prospectively collected data of patients with mild to severe TBI. Data include patient demographics, several initial injury severity metrics, daily laboratory values, Glasgow Outcome Score- Extended (GOSE) scores, Functional Status Examination (FSE) scores, and survival to 6 months. Correlations were evaluated between these variables and transfusion of FFP, platelets, packed red blood cells (RBCs), cryoprecipitate, recombinant factor VIIa, and albumin. Ordinal regression was performed to account for potential confounding variables to further define relationships between transfusion status and long-term outcome. By analyzing collected data, mild to moderate coagulopathy was defined as an international normalized ratio 1.4-2.0, moderate thrombocytopenia as platelet count 50 × 10(9)/L to 107 × 10(9)/L, and moderate anemia as 21%-30% hematocrit. Results In patients with mild to moderate laboratory hematological abnormalities, univariate analysis shows significant correlations between poor outcome scores and FFP, platelet, or packed RBC transfusion; the volume of FFP or packed RBCs transfused also correlated with poor outcome. Several measures of initial injury and laboratory abnormalities also correlated with poor outcome. Patient age, initial Glasgow Coma Scale score, and highest recorded serum sodium were included in the ordinal regression model using backward variable selection. In the moderate coagulopathy subgroup, patients transfused with FFP were more likely to have a lower GOSE score relative to those who did not receive a transfusion (OR 5.20 [95% CI 1.72-15.73]). Patients with moderate coagulopathy who received FFP and packed RBCs were even more likely to be have a lower GOSE score (OR 7.17 [95% CI 2.12-24.12]). Moderately anemic patients who received packed RBCs alone were more likely to have a worse long-term functional outcome as determined by GOSE and FSE scores (GOSE: OR 2.41 [95% CI 1.51-3.85]; and FSE: OR 3.27 [95% CI 2.00-5.35]). No transfusion types or combinations were noted to significantly correlate with the 6-month mortality in ordinal regression. Conclusions In TBI patients with moderate coagulopathy, FFP transfusions alone or a combination of FFP and packed RBCs were associated with poorer long-term functional outcomes as measured by the GOSE. Red blood cell transfusions were associated with poor long-term functional outcome in TBI patients with moderate anemia. Platelet transfusion in patients with moderate thrombocytopenia was not significantly associated with outcome. Although transfusion is beneficial to many patients with severe hematological abnormalities, it is not without risk, and the indications for transfusion should be carefully considered in patients with moderate hematological abnormalities.

Brain morphometry changes and depressive symptoms after traumatic brain injury.

Traumatic brain injury (TBI) is associated with an increased risk of depressive symptoms. Recent imaging studies on spontaneous depression have implicated several brain structures; however, few studies have done the same for post-TBI depression. We report on a pilot observational study correlating atrophy of brain regions of interest in subjects after TBI with depressive symptoms measured by the Beck Depression Inventory-II. Regional brain volumes were calculated on both acute and 6-month MRI using an automated segmentation algorithm (FreeSurfer). Percent volume changes in brain regions were correlated with BDI-II scores using Spearman's rank order correlation coefficient. Correction for multiple comparisons was performed using the false discovery rate (FDR). Three regions of interest (left rostral anterior cingulate and bilateral orbitofrontal cortex) were found to be significantly correlated with depressive symptoms (FDR 0.05). With FDR 0.1, six regions were significantly correlated. The use of volumetric analysis of brain regions of interest to study post-TBI depression is worthy of further study. Regions associated with depressive symptoms in this pilot study were similar to those implicated in study of spontaneous depression.

Diffusion tensor imaging biomarkers for traumatic axonal injury: analysis of three analytic methods.

Traumatic axonal injury (TAI) is a common mechanism of traumatic brain injury not readily identified using conventional neuroimaging modalities. Novel imaging modalities such as diffusion tensor imaging (DTI) can detect microstructural compromise in white matter (WM) in various clinical populations including TAI. DTI-derived data can be analyzed using global methods (i.e., WM histogram or voxel-based approaches) or a regional approach (i.e., tractography). While each of these methods produce qualitatively comparable results, it is not clear which is most useful in clinical research and ultimately in clinical practice. This study compared three methods of analyzing DTI-derived data with regard to detection of WM injury and their association with clinical outcomes. Thirty patients with TAI and 19 demographically similar normal controls were scanned using a 3 Tesla magnet. Patients were scanned approximately eight months postinjury, and underwent an outcomes assessment at that time. Histogram analysis of fractional anisotropy (FA) and mean diffusivity showed global WM integrity differences between patients and controls. Voxel-based and tractography analyses showed significant decreases in FA within centroaxial structures involved in TAI. All three techniques were associated with functional and cognitive outcomes. DTI measures of microstructural integrity appear robust, as the three analysis techniques studied showed adequate utility for detecting WM injury.

Assessing spatial relationships between axonal integrity, regional brain volumes, and neuropsychological outcomes after traumatic axonal injury.

Diffuse traumatic axonal injury (TAI) is a type of traumatic brain injury (TBI) characterized predominantly by white matter damage. While TAI is associated with cerebral atrophy, the relationship between gray matter volumes and TAI of afferent or efferent axonal pathways remains unknown. Moreover, it is unclear if deficits in cognition are associated with post-traumatic brain volumes in particular regions. The goal of this study was to determine the relationship between markers of TAI and volumes of cortical and subcortical structures, while also assessing the relationship between cognitive outcomes and regional brain volumes. High-resolution magnetic resonance imaging scans were performed in 24 patients with TAI within 1 week of injury and were repeated 8 months later. Diffusion tensor imaging (DTI) tractography was used to reconstruct prominent white matter tracts and calculate their fractional anisotropy (FA) and mean diffusivity (MD) values. Regional brain volumes were computed using semi-automated morphometric analysis. Pearson's correlation coefficients were used to assess associations between brain volumes, white matter integrity (i.e., FA and MD), and neuropsychological outcomes. Post-traumatic volumes of many gray matter structures were associated with chronic damage to related white matter tracts, and less strongly associated with measures of white matter integrity in the acute scans. For example, left and right hippocampal volumes correlated with FA in the fornix body (r = 0.600, p = 0.001; r = 0.714, p < 0.001, respectively). In addition, regional brain volumes were associated with deficits in corresponding neuropsychological domains. Our results suggest that TAI may be a primary mechanism of post-traumatic atrophy, and provide support for regional morphometry as a biomarker for cognitive outcome after injury.

Regionally selective atrophy after traumatic axonal injury.

OBJECTIVES: To determine the spatial distribution of cortical and subcortical volume loss in patients with diffuse traumatic axonal injury and to assess the relationship between regional atrophy and functional outcome. DESIGN: Prospective imaging study. Longitudinal changes in global and regional brain volumes were assessed using high-resolution magnetic resonance imaging-based morphometric analysis. SETTING: Inpatient traumatic brain injury unit. PATIENTS OR OTHER PARTICIPANTS: Twenty-five patients with diffuse traumatic axonal injury and 22 age- and sex-matched controls. MAIN OUTCOME MEASURE: Changes in global and regional brain volumes between initial and follow-up magnetic resonance imaging were used to assess the spatial distribution of posttraumatic volume loss. The Glasgow Outcome Scale-Extended score was the primary measure of functional outcome. RESULTS: Patients underwent substantial global atrophy with mean whole-brain parenchymal volume loss of 4.5% (95% confidence interval, 2.7%-6.3%). Decreases in volume (at a false discovery rate of 0.05) were seen in several brain regions including the amygdala, hippocampus, thalamus, corpus callosum, putamen, precuneus, postcentral gyrus, paracentral lobule, and parietal and frontal cortices, while other regions such as the caudate and inferior temporal cortex were relatively resistant to atrophy. Loss of whole-brain parenchymal volume was predictive of long-term disability, as was atrophy of particular brain regions including the inferior parietal cortex, pars orbitalis, pericalcarine cortex, and supramarginal gyrus. CONCLUSION: Traumatic axonal injury leads to substantial posttraumatic atrophy that is regionally selective rather than diffuse, and volume loss in certain regions may have prognostic value for functional recovery.

Transfusions and long-term functional outcomes in traumatic brain injury.

OBJECT: In this paper, the authors' goal was to examine the relationship between transfusion and long-term functional outcomes in moderately anemic patients (lowest hematocrit [HCT] level 21-30%) with traumatic brain injury (TBI). While evidence suggests that transfusions are associated with poor hospital outcomes, no study has examined transfusions and long-term functional outcomes in this population. The preferred transfusion threshold remains controversial. METHODS: The authors performed a retrospective review of patients who were admitted with TBI between September 2005 and November 2007, extracting data such as HCT level, status of red blood cell transfusion, admission Glasgow Coma Scale (GCS) score, serum glucose, and length of hospital stay. Outcome measures assessed at 6 months were Glasgow Outcome Scale-Extended score, Functional Status Examination score, and patient death. A multivariate generalized linear model controlling for confounding variables was used to assess the association between transfusion and outcome. RESULTS: During the study period, 292 patients were identified, and 139 (47.6%) met the criteria for moderate anemia. Roughly half (54.7%) underwent transfusions. Univariate analyses showed significant correlations between outcome score and patient age, admission GCS score, head Abbreviated Injury Scale score, number of days with an HCT level < 30%, highest glucose level, number of days with a glucose level > 200 mg/dl, length of hospital stay, number of patients receiving a transfusion, and transfusion volume. In multivariate analysis, admission GCS score, receiving a transfusion, and transfusion volume were the only variables associated with outcome (F = 2.458, p = 0.007; F = 11.694, p = 0.001; and F = 1.991, p = 0.020, respectively). There was no association between transfusion and death. CONCLUSIONS: Transfusions may contribute to poor long-term functional outcomes in anemic patients with TBI. Transfusion strategies should be aimed at patients with symptomatic anemia or physiological compromise, and transfusion volume should be minimized.

Physiologic and functional outcome correlates of brain tissue hypoxia in traumatic brain injury.

OBJECTIVE: Assess the prevalence of brain tissue hypoxia in patients with severe traumatic brain injuries (TBI), and to characterize the relationship between brain tissue hypoxia and functional outcome. DESIGN: Retrospective review of severe TBI patients. SETTING: Intensive care unit of a level I trauma center. PATIENTS: Twenty-seven patients with severe TBI requiring intracranial pressure (ICP) monitoring. Median age was 22 yrs, and a majority (63%) had traumatic subarachnoid hemorrhage. INTERVENTIONS: Hourly assessments of ICP, brain tissue oxygen, mean arterial pressure, fraction of inspired oxygen (FiO2), partial pressure of arterial carbon dioxide (PaCO2), and hemoglobin concentration (hemoglobin) were recorded. Outcome was assessed 6-9 months postinjury. MEASUREMENTS AND MAIN RESULTS: Mean (SD) ICP and BTpO2 were 13.7 (6.6) cm H2O and 30.8 (13.6) mm Hg. A total of 13.5% (379) of the BTpO2 values recorded were < 20 mm Hg, only 86 of which were associated with ICP > or = 20 cm H2O. This prevalence was comparable with episodes of ICP elevations above 20 cm H2O (14.1%, 397). Hypoxic episodes were more common when cerebral perfusion pressure was below 60 mm Hg (relative risk = 3.0, p < 0.0001). We did not find an association in hypoxic risk and hemoglobin in the range of 7-12 g/dL or PaCO2 in the range of 25-40 mm Hg. Subjects with hourly episodes (epochs) of hypoxia > 20% of the time had poorer scores on outcome measures compared with those with fewer hypoxic epochs. CONCLUSIONS: Hypoxic episodes are common after severe TBI, and most are independent of ICP elevations. Most episodes of hypoxia occur while cerebral perfusion pressure and mean arterial pressure are within the accepted target range. There is no clear association between PaCO2 and hemoglobin with BTpO2. The young age and high prevalence of traumatic subarachnoid hemorrhage in this cohort may limit its generalizability. Increased frequency of hypoxic episodes is associated with poor functional outcome.

Development and evaluation of a study design typology for human research.

A systematic classification of study designs would be useful for researchers, systematic reviewers, readers, and research administrators, among others. As part of the Human Studies Database Project, we developed the Study Design Typology to standardize the classification of study designs in human research. We then performed a multiple observer masked evaluation of active research protocols in four institutions according to a standardized protocol. Thirty-five protocols were classified by three reviewers each into one of nine high-level study designs for interventional and observational research (e.g., N-of-1, Parallel Group, Case Crossover). Rater classification agreement was moderately high for the 35 protocols (Fleiss' kappa = 0.442) and higher still for the 23 quantitative studies (Fleiss' kappa = 0.463). We conclude that our typology shows initial promise for reliably distinguishing study design types for quantitative human research.

Cerebral atrophy after traumatic white matter injury: correlation with acute neuroimaging and outcome.

Traumatic brain injury (TBI) is a pathologically heterogeneous disease, including injury to both neuronal cell bodies and axonal processes. Global atrophy of both gray and white matter is common after TBI. This study was designed to determine the relationship between neuroimaging markers of acute diffuse axonal injury (DAI) and cerebral atrophy months later. We performed high-resolution magnetic resonance imaging (MRI) at 3 Tesla (T) in 20 patients who suffered non-penetrating TBI, during the acute (within 1 month after the injury) and chronic stage (at least 6 months after the injury). Volume of abnormal fluid-attenuated inversion-recovery (FLAIR) signal seen in white matter in both acute and follow-up scans was quantified. White and gray matter volumes were also quantified. Functional outcome was measured using the Functional Status Examination (FSE) at the time of the chronic scan. Change in brain volumes, including whole brain volume (WBV), white matter volume (WMV), and gray matter volume (GMV), correlates significantly with acute DAI volume (r = -0.69, -0.59, -0.58, respectively; p <0.01 for all). Volume of acute FLAIR hyperintensities correlates with volume of decreased FLAIR signal in the follow-up scans (r = -0.86, p < 0.001). FSE performance correlates with acute hyperintensity volume and chronic cerebral atrophy (r = 0.53, p = 0.02; r = -0.45, p = 0.03, respectively). Acute axonal lesions measured by FLAIR imaging are strongly predictive of post-traumatic cerebral atrophy. Our findings suggest that axonal pathology measured as white matter lesions following TBI can be identified using MRI, and may be a useful measure for DAI-directed therapies.

Impact of age on long-term recovery from traumatic brain injury.

OBJECTIVE: To determine whether older persons are at increased risk for progressive functional decline after traumatic brain injury (TBI). DESIGN: Longitudinal cohort study. SETTING: Traumatic Brain Injury Model Systems (TBIMS) rehabilitation centers. PARTICIPANTS: Subjects enrolled in the TBIMS national dataset. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Disability Rating Scale (DRS), FIM instrument cognitive items, and the Glasgow Outcome Scale-Extended. RESULTS: Participants were separated into 3 age tertiles: youngest (16-26y), intermediate (27-39y), and oldest (> or =40y). DRS scores were comparable across age groups at admission to a rehabilitation center. The oldest group was slightly more disabled at discharge from rehabilitation despite having less severe acute injury severity than the younger groups. Although DRS scores for the 2 younger groups improved significantly from year 1 to year 5, the greatest magnitude of improvement in disability was seen among the youngest group. In addition, after dividing patients into groups according to whether their DRS scores improved (13%), declined (10%), or remained stable (77%) over time, the likelihood of decline was found to be greater for the 2 older groups than for the youngest group. A multiple regression model showed that age has a significant negative influence on DRS score 5 years post-TBI after accounting for the effects of covariates. CONCLUSIONS: This study supported our primary hypothesis that older patients show greater decline over the first 5 years after TBI than younger patients. In addition, the greatest amount of improvement in disability was observed among the youngest group of survivors. These results suggest that TBI survivors, especially older patients, may be candidates for neuroprotective therapies after TBI.

Usefulness of the abbreviated injury score and the injury severity score in comparison to the Glasgow Coma Scale in predicting outcome after traumatic brain injury.

BACKGROUND: Assessment of injury severity is important in the management of patients with brain trauma. We aimed to analyze the usefulness of the head abbreviated injury score (AIS), the injury severity score (ISS), and the Glasgow Coma Scale (GCS) as measures of injury severity and predictors of outcome after traumatic brain injury (TBI). METHODS: Data were prospectively collected from 410 patients with TBI. AIS, ISS, and GCS were recorded at admission. Subjects' outcomes after TBI were measured using the Glasgow Outcome Scale (GOS-E) at 12 months postinjury. Uni- and multivariate analyses were performed. RESULTS: Outcome information was obtained from 270 patients (66%). ISS was the best predictor of GOS-E (rs = -0.341, p < 0.001), followed by GCS score (rs = 0.227, p < 0.001), and head AIS (rs = -0.222, p < 0.001). When considered in combination, GCS score and ISS modestly improved the correlation with GOS-E (R = 0.335, p < 0.001). The combination of GCS score and head AIS had a similar effect (R = 0.275, p < 0.001). Correlations were stronger from patients 8). CONCLUSIONS: GCS score, AIS, and ISS are weakly correlated with 12-month outcome. However, anatomic measures modestly outperform GCS as predictors of GOS-E. The combination of GCS and AIS/ISS correlate with outcome better than do any of the three measures alone. Results support the addition of anatomic measures such as AIS and ISS in clinical studies of TBI. Additionally, most of the variance in outcome is not accounted for by currently available measures of injury severity.

Magnetic resonance imaging of diffuse axonal injury: quantitative assessment of white matter lesion volume.

Diffuse axonal injury (DAI) is a common mechanism of traumatic brain injury (TBI) for which there is no well-accepted anatomic measures of injury severity. The present study aims to quantitatively assess DAI by measuring white matter lesion volume visible in fluid-attenuated inversion recovery (FLAIR) weighted images and to determine whether higher lesion volumes are associated with unfavorable functional outcome 6 months after injury. Twenty-four patients who experienced moderate to severe TBI without extra-axial or major cortical contusions were included in this study. Lesion volume was assessed by quantifying areas of hyperintensities in the white matter utilizing digitized FLAIR images. Two independent raters processed the magnetic resonance (MR) images and determined the total DAI volume. Functional outcome was assessed at 6 months after injury using the Glasgow Outcome Scale-Extended (GOSE). Interclass correlation analyses showed very high interrater reliability for each measure between the two raters (Interclass Correlation Coefficient = 0.95, p

Ethnic differences in rehabilitation placement and outcome after TBI.

OBJECTIVE: To determine whether race/ethnicity and proficiency with the English language influence access to rehabilitation services, and ultimately outcome after traumatic brain injury (TBI). DESIGN: A retrospective correlational investigation. SETTING AND PARTICIPANTS: Postrehabilitation outpatients with blunt TBI. A total of 476 patients were examined 6 months postinjury, of which 109 (23%) were Hispanics, and of those 42 were predominantly Spanish speaking. MAIN OUTCOME MEASURES: Access to rehabilitation services, Glasgow Outcome Scale-Extended. RESULTS: Insurance, age, and injury severity had the greatest influence on receipt of rehabilitation services; however, higher rates of severe disability were found among Hispanics and Spanish speakers than non-Hispanic whites and non-Hispanic English speakers, respectively. CONCLUSIONS: Insurance status has a larger influence on receipt of rehabilitation services than ethnicity or proficiency with the English language, but language proficiency is a significant predictor of severe disability.

Functional outcome scales in traumatic brain injury: a comparison of the Glasgow Outcome Scale (Extended) and the Functional Status Examination.

Clinical trials aimed at developing therapies for traumatic brain injury (TBI) require outcome measures that are reliable, validated, and easily administered. The most widely used of these measures, the Glasgow Outcome Scale (GOS) and the GOS-Extended (GOS-E), have been criticized as suffering from ceiling effects. In an attempt to develop a more useful and dynamic outcome measure, the Functional Status Examination (FSE) was developed, which grades outcome across 10 functional domains. The FSE has been demonstrated to be reliable and sensitive in monitoring recovery after TBI. This manuscript compares FSE with GOS-E in a cohort of patients with a wide range of injury severities. 177 individuals who survived at least 6 months after TBI were studied. The FSE and GOS-E were administered 6-12 months after injury. FSE and GOS-E scores correlated well with each other. FSE scores were distributed throughout the range, indicating that ceiling and floor effects were not present. Physiologic measures of injury severity (Glasgow Coma Score [GCS]) did not correlate with anatomic measures (Abbreviated Injury Scale [AIS] and Injury Severity Score [ISS]). GCS correlated weakly with both outcome measures, but AIS/ISS did not. We conclude that FSE and GOS-E are reliable outcome measures for TBI survivors, and FSE may offer some advantages over GOS-E due its ability to provide a more detailed description of deficits. The majority of the variance in outcome is not accounted for by currently available measures of injury severity.

Evaluation of seizure-like episodes in survivors of moderate and severe traumatic brain injury.

BACKGROUND: Transient paroxysmal alterations of consciousness or behavior are common sequelae of moderate and severe traumatic brain injury (TBI). Clinicians caring for patients with such episodes often diagnose them as epileptic seizures, a frequent and well-studied complication of TBI. As it is difficult to confirm this diagnosis, antiepileptic drugs are often used empirically. However, as such therapy is frequently ineffective, we studied the usefulness of prolonged video electroencephalogram (VEEG) monitoring in the clinical management of paroxysmal behaviors in TBI survivors. METHODS: Records of patients referred evaluation in an epilepsy monitoring unit for management of medically intractable epilepsy were retrospectively reviewed. Patients with a documented history of moderate-to-severe brain injury preceding the onset of epilepsy were identified. These patients were studied by simultaneous videotape and scalp electroencephalographic recordings, and the majority also underwent magnetic resonance imaging and neuropsychologic studies. RESULTS: Of the 1858 consecutive admissions over a 66-month period, 127 (7%) fulfilled enrollment criteria. VEEG monitoring was conducted for an average of 4.6 days. Monitoring was successful in establishing a diagnosis in 82% of the cases referred: 62% had focal seizures, 6% had generalized seizures, and 33% had psychogenic nonepileptic seizures. Of those with temporal lobe epilepsy, 53% had mesial temporal sclerosis, as shown by magnetic resonance imaging. CONCLUSIONS: VEEG is a useful procedure in the evaluation of TBI survivors with spells. The yield of diagnoses that may alter treatment is substantial. Additionally, mesial temporal sclerosis is associated with TBI. Given the variety of seizure types found in survivors of moderate-to-severe TBI, obtaining specific diagnosis of seizure type by VEEG monitoring impacts treatment options.