Predicting Functional Dependency in Patients with Disorders of Consciousness: A TBI-Model Systems and TRACK-TBI Study.

OBJECTIVE: It is not currently possible to predict long-term functional dependency in patients with disorders of consciousness (DoC) after traumatic brain injury (TBI). Our objective was to fit and externally validate a prediction model for 1-year dependency in patients with DoC ≥ 2 weeks after TBI. METHODS: We included adults with TBI enrolled in TBI Model Systems (TBI-MS) or Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) studies who were not following commands at rehabilitation admission or 2 weeks post-injury, respectively. We fit a logistic regression model in TBI-MS and validated it in TRACK-TBI. The primary outcome was death or dependency at 1 year post-injury, defined using the Disability Rating Scale. RESULTS: In the TBI-MS Discovery Sample, 1,960 participants (mean age 40 [18] years, 76% male, 68% white) met inclusion criteria, and 406 (27%) were dependent 1 year post-injury. In a TBI-MS held out cohort, the dependency prediction model's area under the receiver operating characteristic curve was 0.79 (95% CI 0.74-0.85), positive predictive value was 53% and negative predictive value was 86%. In the TRACK-TBI external validation (n = 124, age 40 [16] years, 77% male, 81% white), the area under the receiver operating characteristic curve was 0.66 (0.53, 0.79), equivalent to the standard IMPACTcore + CT score (p = 0.8). INTERPRETATION: We developed a 1-year dependency prediction model using the largest existing cohort of patients with DoC after TBI. The sensitivity and negative predictive values were greater than specificity and positive predictive values. Accuracy was diminished in an external sample, but equivalent to the IMPACT model. Further research is needed to improve dependency prediction in patients with DoC after TBI. ANN NEUROL 2023;94:1008-1023.

Predicting Functional Dependency in Patients with Disorders of Consciousness: A TBI-Model Systems and TRACK-TBI Study.

Importance: There are currently no models that predict long-term functional dependency in patients with disorders of consciousness (DoC) after traumatic brain injury (TBI). Objective: Fit, test, and externally validate a prediction model for 1-year dependency in patients with DoC 2 or more weeks after TBI. Design: Secondary analysis of patients enrolled in TBI Model Systems (TBI-MS, 1988-2020, Discovery Sample) or Transforming Research and Clinical Knowledge in TBI (TRACK-TBI, 2013-2018, Validation Sample) and followed 1-year post-injury. Setting: Multi-center study at USA rehabilitation hospitals (TBI-MS) and acute care hospitals (TRACK-TBI). Participants: Adults with TBI who were not following commands at rehabilitation admission (TBI-MS; days post-injury vary) or 2-weeks post-injury (TRACK-TBI). Exposures: In the TBI-MS database (model fitting and testing), we screened demographic, radiological, clinical variables, and Disability Rating Scale (DRS) item scores for association with the primary outcome. Main Outcome: The primary outcome was death or complete functional dependency at 1-year post-injury, defined using a DRS-based binary measure (DRS Depend ), indicating need for assistance with all activities and concomitant cognitive impairment. Results: In the TBI-MS Discovery Sample, 1,960 subjects (mean age 40 [18] years, 76% male, 68% white) met inclusion criteria and 406 (27%) were dependent at 1-year post-injury. A dependency prediction model had an area under the receiver operating characteristic curve (AUROC) of 0.79 [0.74, 0.85], positive predictive value of 53%, and negative predictive value of 86% for dependency in a held-out TBI-MS Testing cohort. Within the TRACK-TBI external validation sample (N=124, age 40 [16], 77% male, 81% white), a model modified to remove variables not collected in TRACK-TBI, had an AUROC of 0.66 [0.53, 0.79], equivalent to the gold-standard IMPACT core+CT score (0.68; 95% AUROC difference CI: -0.2 to 0.2, p=0.8). Conclusions and Relevance: We used the largest existing cohort of patients with DoC after TBI to develop, test and externally validate a prediction model of 1-year dependency. The model’s sensitivity and negative predictive value were greater than specificity and positive predictive value. Accuracy was diminished in an external sample, but equivalent to the best-available models. Further research is needed to improve dependency prediction in patients with DoC after TBI.

Rapid Activation of Neuroinflammation in Stroke: Plasma and Extracellular Vesicles Obtained on a Mobile Stroke Unit.

BACKGROUND: Neuroinflammation is ubiquitous in acute stroke and worsens outcome. However, the precise timing of the inflammatory response is unknown, hindering the design of acute anti-inflammatory therapeutic interventions. We sought to identify the onset of the neuroinflammatory cascade using a mobile stroke unit. METHODS: The study is a proof-of-concept, cohort investigation of ultra-early blood- and extracellular vesicle-derived markers of neuroinflammation and outcome in acute stroke. Blood was obtained, prehospital, on an mobile stroke unit. Outcomes were biomarker concentrations, modified Rankin Scale score, and National Institutes of Health Stroke Scale score. RESULTS: Forty-one adults were analyzed, including 15 patients treated on the mobile stroke unit between August 2021 and April 2022, and 26 healthy controls to establish biomarker reference levels. Median patient age was 74 (range, 36-97) years, 60% were female, and 80% White. Ten (67%) were diagnosed as stroke, with 8 (53%) confirmed and 2 likely transient ischemic attack or stroke averted by thrombolysis; 5 were stroke mimics. For strokes, median initial National Institutes of Health Stroke Scale score was 11 (range, 4-19) and 6 (75%) received tPA (tissue-type plasminogen activator). Blood was obtained a median of 58 (range, 36-133) minutes after symptom onset. Within 36 minutes after stroke, plasma IL-6 (interleukin-6), neurofilament light chain, UCH-L1 (ubiquitin C-terminal hydrolase L1), and GFAP (glial fibrillary acidic protein) were elevated by as much as 10 times normal. In EVs, MMP-9 (matrix metalloproteinase-9), CXCL4 (chemokine (C-X-C motif) ligand 4), CRP (C-reactive protein), IL-6, OPN (osteopontin), and PECAM1 (platelet and endothelial cell adhesion molecule 1) were elevated. Inflammatory markers increased rapidly in the first 2 hours and continued rising for 24 hours. CONCLUSIONS: The neuroinflammatory cascade was found to be activated within 36 to 133 minutes after stroke and progresses rapidly. This is earlier than observed previously in humans and suggests injury from neuroinflammation occurs faster than had been surmised. These findings could inform development of acute immunomodulatory stroke therapies and lead to new diagnostic tools and improved outcomes.

Phenotype and Neuronal Cytotoxic Function of Glioblastoma Extracellular Vesicles.

Glioblastoma (GBM) is the most aggressive and lethal form of brain tumor. Extracellular vesicles (EVs) released by tumor cells play a critical role in cellular communication in the tumor microenvironment promoting tumor progression and invasion. We hypothesized that GBM EVs possess unique characteristics which exert effects on endogenous CNS cells including neurons, producing dose-dependent neuronal cytotoxicity. We purified EVs from the plasma of 20 GBM patients, 20 meningioma patients, and 21 healthy controls, and characterized EV phenotypes by electron microscopy, nanoparticle tracking analysis, protein concentration, and proteomics. We evaluated GBM EV functions by determining their cytotoxicity in primary neurons and the neuroblastoma cell line SH-SY5Y. In addition, we determined levels of IgG antibodies in the plasma in GBM (n = 82), MMA (n = 83), and controls (non-tumor CNS disorders and healthy donors, n = 50) with capture ELISA. We discovered that GBM plasma EVs are smaller in size and had no relationship between size and concentration. Importantly, GBM EVs purified from both plasma and tumor cell lines produced IgG-mediated, complement-dependent apoptosis and necrosis in primary human neurons, mouse brain slices, and neuroblastoma cells. The unique phenotype of GBM EVs may contribute to its neuronal cytotoxicity, providing insight into its role in tumor pathogenesis.

Comparison of Common Outcome Measures for Assessing Independence in Patients Diagnosed with Disorders of Consciousness: A Traumatic Brain Injury Model Systems Study.

Patients with disorders of consciousness (DoC) after traumatic brain injury (TBI) recover to varying degrees of functional dependency. Dependency is difficult to measure but critical for interpreting clinical trial outcomes and prognostic counseling. In participants with DoC (i.e., not following commands) enrolled in the TBI Model Systems National Database (TBIMS NDB), we used the Functional Independence Measure (FIM®) as the reference to evaluate how accurately the Glasgow Outcome Scale-Extended (GOSE) and Disability Rating Scale (DRS) assess dependency. Using the established FIM-dependency cut-point of <80, we measured the classification performance of literature-derived GOSE and DRS cut-points at 1-year post-injury. We compared the area under the receiver operating characteristic curve (AUROC) between the DRSDepend, a DRS-derived marker of dependency, and the data-derived optimal GOSE and DRS cut-points. Of 18,486 TBIMS participants, 1483 met inclusion criteria (mean [standard deviation (SD)] age = 38 [18] years; 76% male). The sensitivity of GOSE cut-points of ≤3 and ≤4 (Lower Severe and Upper Severe Disability, respectively) for identifying FIM-dependency were 97% and 98%, but specificities were 73% and 51%, respectively. The sensitivity of the DRS cut-point of ≥12 (Severe Disability) for identifying FIM-dependency was 60%, but specificity was 100%. The DRSDepend had a sensitivity of 83% and a specificity of 94% for classifying FIM-dependency, with a greater AUROC than the data-derived optimal GOSE (≤3, p = 0.01) and DRS (≥10, p = 0.008) cut-points. Commonly used GOSE and DRS cut-points have limited specificity or sensitivity for identifying functional dependency. The DRSDepend identifies FIM-dependency more accurately than the GOSE and DRS cut-points, but requires further validation.

Cytokine-Laden Extracellular Vesicles Predict Patient Prognosis after Cerebrovascular Accident.

BACKGROUND: A major contributor to disability after hemorrhagic stroke is secondary brain damage induced by the inflammatory response. Following stroke, global increases in numerous cytokines-many associated with worse outcomes-occur within the brain, cerebrospinal fluid, and peripheral blood. Extracellular vesicles (EVs) may traffic inflammatory cytokines from damaged tissue within the brain, as well as peripheral sources, across the blood-brain barrier, and they may be a critical component of post-stroke neuroinflammatory signaling. METHODS: We performed a comprehensive analysis of cytokine concentrations bound to plasma EV surfaces and/or sequestered within the vesicles themselves. These concentrations were correlated to patient acute neurological condition by the Glasgow Coma Scale (GCS) and to chronic, long-term outcome via the Glasgow Outcome Scale-Extended (GOS-E). RESULTS: Pro-inflammatory cytokines detected from plasma EVs were correlated to worse outcomes in hemorrhagic stroke patients. Anti-inflammatory cytokines detected within EVs were still correlated to poor outcomes despite their putative neuroprotective properties. Inflammatory cytokines macrophage-derived chemokine (MDC/CCL2), colony stimulating factor 1 (CSF1), interleukin 7 (IL7), and monokine induced by gamma interferon (MIG/CXCL9) were significantly correlated to both negative GCS and GOS-E when bound to plasma EV membranes. CONCLUSIONS: These findings correlate plasma-derived EV cytokine content with detrimental outcomes after stroke, highlighting the potential for EVs to provide cytokines with a means of long-range delivery of inflammatory signals that perpetuate neuroinflammation after stroke, thus hindering recovery.

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.

Differentiation of psychogenic nonepileptic attacks from status epilepticus among patients intubated for convulsive activity.

BACKGROUND AND OBJECTIVE: Patients with psychogenic nonepileptic attacks (PNEA) sometimes receive aggressive treatment leading to intubation. This study aimed to identify patient characteristics that can help differentiate PNEA from status epilepticus (SE). METHODS: We retrospectively identified patients with a final diagnosis of PNEA or SE, who were intubated for emergent convulsive symptoms and underwent continuous electroencephalography (cEEG) between 2012 and 2017. Patients who had acute brain injury or progressive brain disease as the cause of SE were excluded. We compared clinical features and laboratory values between the two groups, and identified risk factors for PNEA-related convulsive activity. RESULTS: Over a six-year period, 24 of 148 consecutive patients (16%) intubated for convulsive activity had a final diagnosis of PNEA rather than SE. Compared to patients intubated for SE, intubated PNEA patients more likely were <50 years of age, female, white, had a history of a psychiatric disorder, had no history of an intracranial abnormality, and had a maximum systolic blood pressure <140 mm Hg (all P < 0.001). Patients with 0-2 of these six risk factors had a 0% (0/88) likelihood of having PNEA, those with 3-4 had a 15% (6/39) chance of having PNEA, and those with 5-6 had an 86% (18/21) chance of having PNEA. Sensitivity for PNEA among those with 5-6 risk factors was 75% (95% CI: 53-89%) and specificity was 98% (95% CI: 93-99%). CONCLUSIONS: In the absence of a clear precipitating brain injury, approximately one in six patients intubated for emergent convulsive symptoms had PNEA rather than SE. Although PNEA cannot be diagnosed only by the presence of these risk factors, these simple characteristics could raise clinical suspicion for PNEA in the appropriate setting. Urgent neurological consultation may prevent unnecessary intubation of this at-risk patient population.

Rhythmic Auditory Stimulation and Gait Training in Traumatic Brain Injury: A Pilot Study.

Rhythmic auditory stimulation (RAS) has been well researched with stroke survivors and individuals who have Parkinson's disease, but little research exists on RAS with people who have experienced traumatic brain injury (TBI). This pilot study aimed to (1) assess the feasibility of the study design and (2) explore potential benefits. This single-arm clinical trial included 10 participants who had a 2-week control period between baseline and pretreatment. Participants had RAS daily for a 2-week treatment period and immediately completed post-treatment assessments. Participants then had a 1-week control period and completed follow-up assessment. The starting cadence was evaluated each day of the intervention period due to the variation in daily functioning in this population. All 10 participants were 1-20 years post-TBI with notable deviations in spatial-temporal aspects of gait including decreased velocity, step symmetry, and cadence. All participants had a high risk of falling as defined by achieving less than 22 on the Functional Gait Assessment (FGA). The outcome measures included the 10-m walk test, spatial and temporal gait parameters, FGA, and Physical Activity Enjoyment Scale. There were no adverse events during the study and gait parameters improved. After the intervention, half of the participants achieved a score of more than 22 on the FGA, indicating that they were no longer at high risk of experiencing falls.

Intravenous Fibrinolysis for Central Retinal Artery Occlusion: A Cohort Study and Updated Patient-Level Meta-Analysis.

BACKGROUND AND PURPOSE: Central retinal artery occlusion results in sudden, painless, usually permanent loss of vision in the affected eye. There is no proven, effective treatment to salvage visual acuity and a clear, unmet need for an effective therapy. In this work, we evaluated the efficacy of intravenous tissue-type plasminogen activator (IV alteplase) in a prospective cohort study and an updated systematic review and meta-analysis. METHODS: We enrolled consecutive patients with acute central retinal artery occlusion within 48 hours of symptoms onset and with a visual acuity of <20/200 from January 2009 until May 2019. The primary outcomes were safety and functional visual acuity recovery. We compared rates of visual recovery between those treated with alteplase within 4.5 hours of symptom onset to those who did not receive alteplase (including an analysis restricted to untreated patients presenting within the window for treatment). We incorporated these results into an updated systematic review and patient-level meta-analysis. RESULTS: We enrolled 112 patients, of whom 25 (22.3% of the cohort) were treated with IV alteplase. One patient had an asymptomatic intracerebral hemorrhage after IV alteplase treatment. Forty-four percent of alteplase-treated patients had recovery of visual acuity when treated within 4.5 hours versus 13.1% of those not treated with alteplase (P=0.003) and 11.6% of those presenting within 4 hours who did not receive alteplase (P=0.03). Our updated patient-level meta-analysis of 238 patients included 67 patients treated with alteplase within 4.5 hours since time last known well with a recovery rate of 37.3%. This favorably compares with a 17.7% recovery rate in those without treatment. In linear regression, earlier treatment correlated with a higher rate of visual recovery (P=0.01). CONCLUSIONS: This study showed that the administration of intravenous alteplase within 4.5 hours of symptom onset is associated with a higher likelihood of a favorable visual outcome for acute central retinal artery occlusion. Our results strongly support proceeding to a randomized, placebo-controlled clinical trial.

Prediction of Symptomatic Venous Thromboembolism in Critically Ill Patients: The ICU-Venous Thromboembolism Score.

OBJECTIVES: To identify risk factors and develop a prediction score for in-hospital symptomatic venous thromboembolism in critically ill patients. DESIGN: Retrospective cohort study. SETTING: Henry Ford Health System, a five-hospital system including 18 ICUs. PATIENTS: We obtained data from the electronic medical record of all adult patients admitted to any ICU (total 264 beds) between January 2015 and March 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Symptomatic venous thromboembolism was defined as deep vein thrombosis, pulmonary embolism, or both, diagnosed greater than 24 hours after ICU admission and confirmed by ultrasound, CT, or nuclear medicine imaging. A prediction score (the ICU-Venous Thromboembolism score) was derived from independent risk factors identified using multivariable logistic regression. Of 37,050 patients who met the eligibility criteria, 529 patients (1.4%) developed symptomatic venous thromboembolism. The ICU-Venous Thromboembolism score consists of six independent predictors: central venous catheterization (5 points), immobilization greater than or equal to 4 days (4 points), prior history of venous thromboembolism (4 points), mechanical ventilation (2 points), lowest hemoglobin during hospitalization greater than or equal to 9 g/dL (2 points), and platelet count at admission greater than 250,000/µL (1 point). Patients with a score of 0-8 (76% of the sample) had a low (0.3%) risk of venous thromboembolism; those with a score of 9-14 (22%) had an intermediate (3.6%) risk of venous thromboembolism (hazard ratio, 6.7; 95% CI, 5.3-8.4); and those with a score of 15-18 (2%) had a high (17.7%) risk of venous thromboembolism (hazard ratio, 28.1; 95% CI, 21.7-36.5). The overall C-statistic of the model was 0.87 (95% CI, 0.85-0.88). CONCLUSIONS: Clinically diagnosed symptomatic venous thromboembolism occurred in 1.4% of this large population of ICU patients with high adherence to chemoprophylaxis. Central venous catheterization and immobilization are potentially modifiable risk factors for venous thromboembolism. The ICU-Venous Thromboembolism score can identify patients at increased risk for venous thromboembolism.

Functional Outcome Trajectories Following Inpatient Rehabilitation for TBI in the United States: A NIDILRR TBIMS and CDC Interagency Collaboration.

OBJECTIVE: To describe trajectories of functioning up to 5 years after traumatic brain injury (TBI) that required inpatient rehabilitation in the United States using individual growth curve models conditioned on factors associated with variability in functioning and independence over time. DESIGN: Secondary analysis of population-weighted data from a multicenter longitudinal cohort study. SETTING: Acute inpatient rehabilitation facilities. PARTICIPANTS: A total of 4624 individuals 16 years and older with a primary diagnosis of TBI. MAIN OUTCOME MEASURES: Ratings of global disability and supervision needs as reported by participants or proxy during follow-up telephone interviews at 1, 2, and 5 years postinjury. RESULTS: Many TBI survivors experience functional improvement through 1 and 2 years postinjury, followed by a decline in functioning and decreased independence by 5 years. However, there was considerable heterogeneity in outcomes across individuals. Factors such as older age, non-White race, lower preinjury productivity, public payer source, longer length of inpatient rehabilitation stay, and lower discharge functional status were found to negatively impact trajectories of change over time. CONCLUSIONS: These findings can inform the content, timing, and target recipients of interventions designed to maximize functional independence after TBI.

Venous Thromboembolism in Neurocritical Care Patients.

BACKGROUND: Venous thromboembolism (VTE) is a potentially life-threatening complication among critically ill patients. Neurocritical care patients are presumed to be at high risk for VTE; however, data regarding risk factors in this population are limited. We designed this study to evaluate the frequency, risk factors, and clinical impact of VTE in neurocritical care patients. METHODS: We obtained data from the electronic medical record of all adult patients admitted to neurological intensive care unit (NICU) at Henry Ford Hospital between January 2015 and March 2018. Venous thromboembolism was defined as deep vein thrombosis, pulmonary embolism, or both diagnosed by Doppler, chest computed tomography (CT) angiography or ventilation-perfusion scan >24 hours after admission. Patients with ICU length of stay <24 hours or who received therapeutic anticoagulants or were diagnosed with VTE within 24 hours of admission were excluded. RESULTS: Among 2188 consecutive NICU patients, 63 (2.9%) developed VTE. Prophylactic anticoagulant use was similar in patients with and without VTE (95% vs 92%; P = .482). Venous thromboembolism was associated with higher mortality (24% vs 13%, P = .019), and longer ICU (12 [interquartile range, IQR 5-23] vs 3 [IQR 2-8] days, P < .001) and hospital (22 [IQR 15-36] vs 8 [IQR 5-15] days, P < .001) length of stay. In a multivariable analysis, potentially modifiable predictors of VTE included central venous catheterization (odds ratio [OR] 3.01; 95% confidence interval [CI], 1.69-5.38; P < .001) and longer duration of immobilization (Braden activity score <3, OR 1.07 per day; 95% CI, 1.05-1.09; P < .001). Nonmodifiable predictors included higher International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) scores (which accounts for age >60, prior VTE, cancer and thrombophilia; OR 1.66; 95% CI, 1.40-1.97; P < .001) and body mass index (OR 1.05; 95% CI, 1.01-1.08; P = .007). CONCLUSIONS: Despite chemoprophylaxis, VTE still occurred in 2.9% of neurocritical care patients. Longer duration of immobilization and central venous catheterization are potentially modifiable risk factors for VTE in critically ill neurological patients.

Return to Productivity Projections for Individuals With Moderate to Severe TBI Following Inpatient Rehabilitation: A NIDILRR TBIMS and CDC Interagency Collaboration.

OBJECTIVE: Return to work and school following traumatic brain injury (TBI) is an outcome of central importance both to TBI survivors and to society. The current study estimates the probability of returning to productivity over 5 years following moderate to severe brain injury. DESIGN: A secondary longitudinal analysis using random effects modeling, that is, individual growth curve analysis based on a sample of 2542 population-weighted individuals from a multicenter cohort study. SETTING: Acute inpatient rehabilitation facilities. PARTICIPANTS: Individuals 16 years and older with a primary diagnosis of TBI who were engaged in school or work at the time of injury. MAIN OUTCOME MEASURES: Participation in productive activity, defined as employment or school, as reported during follow-up telephone interviews at 1, 2, and 5 years postinjury. RESULTS: Baseline variables, age of injury, race, level of education and occupational category at the time of injury, disability rating at hospital discharge, substance abuse status, and rehabilitation length of stay, are significantly associated with probability of return to productivity. Individual-level productivity trajectories generally indicate that the probability of returning to productivity increases over time. CONCLUSIONS: Results of this study highlight the importance of preinjury occupational status and level of education in returning to productive activity following moderate to severe TBI.

Integration of Real-Time Electronic Health Records and Wireless Technology in a Mobile Stroke Unit.

BACKGROUND: UCHealth's Mobile Stroke Unit (MSU) at University of Colorado Hospital is an ambulance equipped with a computed tomography (CT) scanner and tele-stroke capabilities that began clinical operation in Aurora, Colorado January 2016. As one of the first MSU's in the United States, it was necessary to design unique and dynamic information technology infrastructure. This includes high-speed cellular connectivity, Health Insurance Portability and Accountability Act compliance, cloud-based and remote access to electronic medical records (EMR), and reliable and rapid image transfer. Here we describe novel technologies incorporated into the MSU. Technological data-handling aspects of the MSU were reviewed. Functions evaluated include wireless connectivity while in transit, EMR access and manipulation in the field, CT with image transfer from the MSU to the hospital's Picture Archiving Communication System (PACS), and video and audio communication for neurological assessment. METHODS/RESULTS: The MSU wireless system was designed with redundancy to avoid dropped signals during data transfer. Two separate Internet Protocol destinations with split-tunnel architecture are assigned, for videoconferencing and for EMR data transfer. Brain images acquired in the ambulance CT scanner are transferred initially to an onboard laptop, then via Citrix Receiver to the hospital-based PACS server where they can be viewed in PACS or EMR by the stroke neurologist, neuroradiologist, and other providers. PACS and Radiology Information System are 2 of the XenApps utilized by CT technologists on board the MSU. DISCUSSION/CONCLUSIONS: These technologies will serve as a blueprint for development of similar units elsewhere, and as a framework for improvement in this technology.

Predictive utility of an adapted Marshall head CT classification scheme after traumatic brain injury.

OBJECTIVE: To study the predictive relationship among persons with traumatic brain injury (TBI) between an objective indicator of injury severity (the adapted Marshall computed tomography [CT] classification scheme) and clinical indicators of injury severity in the acute phase, functional outcomes at inpatient rehabilitation discharge, and functional and participation outcomes at 1 year after injury, including death. PARTICIPANTS: The sample involved 4895 individuals who received inpatient rehabilitation following acute hospitalization for TBI and were enrolled in the Traumatic Brain Injury Model Systems National Database between 1989 and 2014. DESIGN: Head CT variables for each person were fit into adapted Marshall CT classification categories I through IV. MAIN MEASURES: Prediction models were developed to determine the amount of variability explained by the CT classification categories compared with commonly used predictors, including a clinical indicator of injury severity. RESULTS: The adapted Marshall classification categories aided only in the prediction of craniotomy or craniectomy during acute hospitalization, otherwise making no meaningful contribution to variance in the multivariable models predicting outcomes at any time point after injury. CONCLUSION: Results suggest that head CT findings classified in this manner do not inform clinical discussions related to functional prognosis or rehabilitation planning after TBI. ABBREVIATIONS: CT: computed tomography; DRS: disability rating scale; EGOS: extended Glasgow outcome scale; FIM: functional independence measure; NDB: National Data Base; PTA: posttraumatic amnesia; RLOS: rehabilitation length of stay; SPOS: semipartial omega squared statistic; TBI: traumatic brain injury; TBIMS: Traumatic Brain Injury Model Systems.

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.

Acute Ischemic Stroke After Moderate to Severe Traumatic Brain Injury: Incidence and Impact on Outcome.

BACKGROUND AND PURPOSE: Traumatic brain injury (TBI) leads to nearly 300 000 annual US hospitalizations and increased lifetime risk of acute ischemic stroke (AIS). Occurrence of AIS immediately after TBI has not been well characterized. We evaluated AIS acutely after TBI and its impact on outcome. METHODS: A prospective database of moderate to severe TBI survivors, admitted to inpatient rehabilitation at 22 Traumatic Brain Injury Model Systems centers and their referring acute-care hospitals, was analyzed. Outcome measures were AIS incidence, duration of posttraumatic amnesia, Functional Independence Measure, and Disability Rating Scale, at rehabilitation discharge. RESULTS: Between October 1, 2007, and March 31, 2015, 6488 patients with TBI were enrolled in the Traumatic Brain Injury Model Systems National Database. One hundred and fifty-nine (2.5%) patients had a concurrent AIS, and among these, median age was 40 years. AIS was associated with intracranial mass effect and carotid or vertebral artery dissection. High-velocity events more commonly caused TBI with dissection. AIS predicted poorer outcome by all measures, accounting for a 13.3-point reduction in Functional Independence Measure total score (95% confidence interval, -16.8 to -9.7; P<0.001), a 1.9-point increase in Disability Rating Scale (95% confidence interval, 1.3-2.5; P<0.001), and an 18.3-day increase in posttraumatic amnesia duration (95% confidence interval, 13.1-23.4; P<0.001). CONCLUSIONS: Ischemic stroke is observed acutely in 2.5% of moderate to severe TBI survivors and predicts worse functional and cognitive outcome. Half of TBI patients with AIS were aged ≤40 years, and AIS patients more often had cervical dissection. Vigilance for AIS is warranted acutely after TBI, particularly after high-velocity events.