Kristen Dams-O'Connor

Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot: Multicenter Implementation of the Common Data Elements for Traumatic Brain Injury

Traumatic brain injury (TBI) is among the leading causes of death and disability worldwide, with enormous negative social and economic impacts. The heterogeneity of TBI combined with the lack of precise outcome measures have been central to the discouraging results from clinical trials. Current approaches to the characterization of disease severity and outcome have not changed in more than three decades. This prospective multicenter observational pilot study aimed to validate the feasibility of implementing the TBI Common Data Elements (TBI-CDEs). A total of 650 subjects who underwent computed tomography (CT) scans in the emergency department within 24 h of injury were enrolled at three level I trauma centers and one rehabilitation center. The TBI-CDE components collected included: 1) demographic, social and clinical data; 2) biospecimens from blood drawn for genetic and proteomic biomarker analyses; 3) neuroimaging studies at 2 weeks using 3T magnetic resonance imaging (MRI); and 4) outcome assessments at 3 and 6 months. We describe how the infrastructure was established for building data repositories for clinical data, plasma biomarkers, genetics, neuroimaging, and multidimensional outcome measures to create a high quality and accessible information commons for TBI research. Risk factors for poor follow-up, TBI-CDE limitations, and implementation strategies are described. Having demonstrated the feasibility of implementing the TBI-CDEs through successful recruitment and multidimensional data collection, we aim to expand to additional study sites. Furthermore, interested researchers will be provided early access to the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) data set for collaborative opportunities to more precisely characterize TBI and improve the design of future clinical treatment trials. (ClinicalTrials.gov Identifier NCT01565551.).

Diffusion Tensor Imaging for Outcome Prediction in Mild Traumatic Brain Injury: A TRACK-TBI Study

We evaluated 3T diffusion tensor imaging (DTI) for white matter injury in 76 adult mild traumatic brain injury (mTBI) patients at the semiacute stage (11.2±3.3 days), employing both whole-brain voxel-wise and region-of-interest (ROI) approaches. The subgroup of 32 patients with any traumatic intracranial lesion on either day-of-injury computed tomography (CT) or semiacute magnetic resonance imaging (MRI) demonstrated reduced fractional anisotropy (FA) in numerous white matter tracts, compared to 50 control subjects. In contrast, 44 CT/MRI-negative mTBI patients demonstrated no significant difference in any DTI parameter, compared to controls. To determine the clinical relevance of DTI, we evaluated correlations between 3- and 6-month outcome and imaging, demographic/socioeconomic, and clinical predictors. Statistically significant univariable predictors of 3-month Glasgow Outcome Scale-Extended (GOS-E) included MRI evidence for contusion (odds ratio [OR] 4.9 per unit decrease in GOS-E; p=0.01), ≥1 ROI with severely reduced FA (OR, 3.9; p=0.005), neuropsychiatric history (OR, 3.3; p=0.02), age (OR, 1.07/year; p=0.002), and years of education (OR, 0.79/year; p=0.01). Significant predictors of 6-month GOS-E included ≥1 ROI with severely reduced FA (OR, 2.7; p=0.048), neuropsychiatric history (OR, 3.7; p=0.01), and years of education (OR, 0.82/year; p=0.03). For the subset of 37 patients lacking neuropsychiatric and substance abuse history, MRI surpassed all other predictors for both 3- and 6-month outcome prediction. This is the first study to compare DTI in individual mTBI patients to conventional imaging, clinical, and demographic/socioeconomic characteristics for outcome prediction. DTI demonstrated utility in an inclusive group of patients with heterogeneous backgrounds, as well as in a subset of patients without neuropsychiatric or substance abuse history.

Risk for late-life re-injury, dementia and death among individuals with traumatic brain injury: a population-based study

Objectives To determine the association of self-reported traumatic brain injury (TBI) with loss of consciousness (LOC) with late-life re-injury, dementia diagnosis and mortality. Design Ongoing longitudinal population-based prospective cohort study. Setting Seattle-area integrated health system. Participants 4225 dementia-free individuals age 65 and older were randomly selected and enrolled between 1994 and 2010. Participants were seen every 2 years, with mean (range) follow-up of 7.4 (0–16) years. 606 (14%) participants reported a lifetime history of TBI with LOC at enrolment. 3466 participants provided information regarding lifetime history of TBI and completed at least one follow-up visit. Main outcome measures Self-reported TBI with LOC after study entry, incident all-cause dementia and Alzheimers disease (AD), and all-cause mortality. Results There were 25 567 person-years of follow-up. History of TBI with LOC reported at study enrolment was associated with increased risk for TBI with LOC during follow-up, with adjusted HRs ranging from 2.54 (95% CI 1.42 to 4.52) for those reporting first injury before age 25 to 3.79 (95% CI 1.89 to 7.61) for those with first injury after age 55. History of TBI with LOC was not associated with elevated risk for developing dementia or AD. There was no association between baseline history of TBI with LOC and mortality, though TBI with LOC since the previous study visit (‘recent TBI’) was associated with increased mortality (HR 2.12, 95% CI 1.62 to 2.78). Conclusions Individuals aged 65 or older who reported a history of TBI with LOC at any time in their lives were at elevated risk of subsequent re-injury. Recent TBI with LOC sustained in older adulthood was associated with increased risk for mortality. Findings support the need for close clinical monitoring of older adults who sustain a TBI with LOC.

Outcome Prediction after Mild and Complicated Mild Traumatic Brain Injury: External Validation of Existing Models and Identification of New Predictors Using the TRACK-TBI Pilot Study

Although the majority of patients with mild traumatic brain injury (mTBI) recover completely, some still suffer from disabling ailments at 3 or 6 months. We validated existing prognostic models for mTBI and explored predictors of poor outcome after mTBI. We selected patients with mTBI from TRACK-TBI Pilot, an unselected observational cohort of TBI patients from three centers in the United States. We validated two prognostic models for the Glasgow Outcome Scale Extended (GOS-E) at 6 months after injury. One model was based on the CRASH study data and another from Nijmegen, The Netherlands. Possible predictors of 3- and 6-month GOS-E were analyzed with univariate and multi-variable proportional odds regression models. Of the 386 of 485 patients included in the study (median age, 44 years; interquartile range, 27-58), 75% (n=290) presented with a Glasgow Coma Score (GCS) of 15. In this mTBI population, both previously developed models had a poor performance (area under the receiver operating characteristic curve, 0.49-0.56). In multivariable analyses, the strongest predictors of lower 3- and 6-month GOS-E were older age, pre-existing psychiatric conditions, and lower education. Injury caused by assault, extracranial injuries, and lower GCS were also predictive of lower GOS-E. Existing models for mTBI performed unsatisfactorily. Our study shows that, for mTBI, different predictors are relevant as for moderate and severe TBI. These include age, pre-existing psychiatric conditions, and lower education. Development of a valid prediction model for mTBI patients requires further research efforts.

Measurement of the glial fibrillary acidic protein and its breakdown products GFAP-BDP biomarker for the detection of traumatic brain injury compared to computed tomography and magnetic resonance imaging

Glial fibrillary acidic protein and its breakdown products (GFAP-BDP) are brain-specific proteins released into serum as part of the pathophysiological response after traumatic brain injury (TBI). We performed a multi-center trial to validate and characterize the use of GFAP-BDP levels in the diagnosis of intracranial injury in a broad population of patients with a positive clinical screen for head injury. This multi-center, prospective, cohort study included patients 16-93 years of age presenting to three level 1 trauma centers with suspected TBI (loss of consciousness, post-trauma amnesia, and so on). Serum GFAP-BDP levels were drawn within 24 h and analyzed, in a blinded fashion, using sandwich enzyme-linked immunosorbent assay. The ability of GFAP-BDP to predict intracranial injury on admission computed tomography (CT) as well as delayed magnetic resonance imaging was analyzed by multiple regression and assessed by the area under the receiver operating characteristic curve (AUC). Utility of GFAP-BDP to predict injury and reduce unnecessary CT scans was assessed utilizing decision curve analysis. A total of 215 patients were included, of which 83% suffered mild TBI, 4% moderate, and 12% severe; mean age was 42.1±18 years. Evidence of intracranial injury was present in 51% of the sample (median Rotterdam Score, 2; interquartile range, 2). GFAP-BDP demonstrated very good predictive ability (AUC=0.87) and demonstrated significant discrimination of injury severity (odds ratio, 1.45; 95% confidence interval, 1.29-1.64). Use of GFAP-BDP yielded a net benefit above clinical screening alone and a net reduction in unnecessary scans by 12-30%. Used in conjunction with other clinical information, rapid measurement of GFAP-BDP is useful in establishing or excluding the diagnosis of radiographically apparent intracranial injury throughout the spectrum of TBI. As an adjunct to current screening practices, GFAP-BDP may help avoid unnecessary CT scans without sacrificing sensitivity (Registry: ClinicalTrials.gov Identifier: NCT01565551).

An introduction to applying individual growth curve models to evaluate change in rehabilitation: a National Institute on Disability and Rehabilitation Research Traumatic Brain Injury Model Systems report.

The abundance of time-dependent information contained in the Spinal Cord Injury and the Traumatic Brain Injury Model Systems National Databases, and the increased prevalence of repeated-measures designs in clinical trials highlight the need for more powerful longitudinal analytic methodologies in rehabilitation research. This article describes the particularly versatile analytic technique of individual growth curve (IGC) analysis. A defining characteristic of IGC analysis is that change in outcome such as functional recovery can be described at both the patient and group levels, such that it is possible to contrast 1 patient with other patients, subgroups of patients, or a group as a whole. Other appealing characteristics of IGC analysis include its flexibility in describing how outcomes progress over time (whether in linear, curvilinear, cyclical, or other fashion), its ability to accommodate covariates at multiple levels of analyses to better describe change, and its ability to accommodate cases with partially missing outcome data. These features make IGC analysis an ideal tool for investigating longitudinal outcome data and to better equip researchers and clinicians to explore a multitude of hypotheses. The goal of this special communication is to familiarize the rehabilitation community with IGC analysis and encourage the use of this sophisticated research tool to better understand temporal change in outcomes.

Prior history of traumatic brain injury among persons in the Traumatic Brain Injury Model Systems National Database

OBJECTIVE To determine the association between demographic, psychosocial, and injury-related characteristics and traumatic brain injury (TBI) occurring prior to a moderate or severe TBI requiring rehabilitation. DESIGN Secondary data analysis. SETTING TBI Model System inpatient rehabilitation facilities. PARTICIPANTS Persons (N=4464) 1, 2, 5, 10, 15, or 20 years after TBI resulting in participation in the TBI Model System National Database. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES History of TBI prior to the TBI Model System Index injury, pre-Index injury demographic and behavioral characteristics, Index injury characteristics, post-Index injury behavioral health and global outcome. RESULTS Twenty percent of the cohort experienced TBIs preceding the TBI Model System Index injury-80% of these were mild and 40% occurred before age 16. Pre- and post-Index injury behavioral issues, especially substance abuse, were highly associated with having had a prior TBI. Greater severity of the pre-Index injury as well as occurrence before age 6 often showed stronger associations. Unexpectedly, pre-Index TBI was associated with less severe Index injuries and better functioning on admission and discharge from rehabilitation. CONCLUSIONS Findings suggest that earlier life TBI may have important implications for rehabilitation after subsequent TBI, especially for anticipating behavioral health issues in the chronic stage of recovery. Results provide additional evidence for the potential consequences of early life TBI, even if mild.

Longitudinal Description of the Glasgow Outcome Scale-Extended for Individuals in the Traumatic Brain Injury Model Systems National Database: A National Institute on Disability and Rehabilitation Research Traumatic Brain Injury Model Systems Study

OBJECTIVE To comprehensively describe the temporal patterns of global outcome after traumatic brain injury (TBI) in the Traumatic Brain Injury Model Systems National Database (TBIMS NDB). DESIGN Longitudinal prospective cohort study. SETTING TBI Model Systems centers. PARTICIPANTS Patients (N=3870) ≥16 years of age with moderate or severe TBI enrolled in the TBIMS NDB. INTERVENTIONS None. MAIN OUTCOME MEASURE Glasgow Outcome Scale-Extended (GOS-E). RESULTS The trajectory of the GOS-E scores is best described with a model of quadratic change, in which scores initially increase and peak approximately 10 years after the first GOS-E assessment, and then decrease. Change occurs most rapidly in the initial and final years of the timeline. There was significant variability in each growth parameter (P<.05). A reduced multilevel model was built, including all covariates (age at first GOS-E assessment, FIM, race, sex, rehabilitation length of stay) that related significantly to the growth parameters. An interactive tool was created to generate individual level trajectories based on various combinations of covariate values. Results provide an individual level account of the chronological progression of TBI outcomes, as measured by the GOS-E. CONCLUSIONS Individual growth curve analysis is a statistically rigorous approach to describe temporal change with respect to the GOS-E at the individual level for participants within the TBIMS NDB. Results indicated that, for individuals in the TBIMS NDB as a group, functional status as measured by the GOS-E initially improves, plateaus, and then begins to decline. Factors such as age at first GOS-E assessment, race, FIM score at rehabilitation admission, and rehabilitation length of stay were found to influence baseline GOS-E scores, as well as the rate and extent of both improvement and decline over time. Additional research may be required to determine the generalizability of these findings and the usefulness of this tool for clinical applications.

The chronic and evolving neurological consequences of traumatic brain injury

Traumatic brain injury (TBI) can have lifelong and dynamic effects on health and wellbeing. Research on the long-term consequences emphasises that, for many patients, TBI should be conceptualised as a chronic health condition. Evidence suggests that functional outcomes after TBI can show improvement or deterioration up to two decades after injury, and rates of all-cause mortality remain elevated for many years. Furthermore, TBI represents a risk factor for a variety of neurological illnesses, including epilepsy, stroke, and neurodegenerative disease. With respect to neurodegeneration after TBI, post-mortem studies on the long-term neuropathology after injury have identified complex persisting and evolving abnormalities best described as polypathology, which includes chronic traumatic encephalopathy. Despite growing awareness of the lifelong consequences of TBI, substantial gaps in research exist. Improvements are therefore needed in understanding chronic pathologies and their implications for survivors of TBI, which could inform long-term health management in this sizeable patient population.

Role and Impact of Cognitive Rehabilitation

Cognitive rehabilitation interventions are theoretically based and empirically validated treatments designed to ameliorate the cognitive, behavioral, and emotional impairments commonly experienced by individuals with traumatic brain injury (TBI). Cognitive rehabilitation can play many roles in facilitating recovery after TBI, such as improving impaired cognitive functions, increasing awareness of injury-related deficits, improving mood, facilitating vocational and community involvement, and reducing the probability of secondary disability. The considerable evidence documenting the impact of cognitive rehabilitation on improving the day-to-day function of individuals with TBI is described.