Neuroimaging of structural pathology and connectomics in traumatic brain injury: Toward personalized outcome prediction.

Recent contributions to the body of knowledge on traumatic brain injury (TBI) favor the view that multimodal neuroimaging using structural and functional magnetic resonance imaging (MRI and fMRI, respectively) as well as diffusion tensor imaging (DTI) has excellent potential to identify novel biomarkers and predictors of TBI outcome. This is particularly the case when such methods are appropriately combined with volumetric/morphometric analysis of brain structures and with the exploration of TBI-related changes in brain network properties at the level of the connectome. In this context, our present review summarizes recent developments on the roles of these two techniques in the search for novel structural neuroimaging biomarkers that have TBI outcome prognostication value. The themes being explored cover notable trends in this area of research, including (1) the role of advanced MRI processing methods in the analysis of structural pathology, (2) the use of brain connectomics and network analysis to identify outcome biomarkers, and (3) the application of multivariate statistics to predict outcome using neuroimaging metrics. The goal of the review is to draw the community's attention to these recent advances on TBI outcome prediction methods and to encourage the development of new methodologies whereby structural neuroimaging can be used to identify biomarkers of TBI outcome

Traumatic Brain Injury Screening Tools in Primary Care

Traumatic brain injuries are a significant health concern, being responsible for over 52,000 deaths each year. Unfortunately, many traumatic brain injuries often go misdiagnosed or undiagnosed. Primary care providers are the principal and first source of medical contact for individuals, meaning that they are vital in the diagnosis of previous traumatic brain injuries in order to prevent future sequelae. There are currently several well-validated screening tools currently available for use by primary care providers. This study uses a self-reported survey to determine which of these tools are used by primary care nurse practitioners from a northern New England state and to compare the results to the suggestions made in current literature. The tools chosen by different primary care providers vary greatly, as do the indications used for initiation of traumatic brain injury screening. There were a total of 17 participants in the study, all of whom were at least masters level prepared nurse practitioners. The average number of years spent in practice was 11.7, with an average of 10.4 of those years in primary care. The most commonly used screening tool was the Mini Mental Status Exam, followed by the Montreal Cognitive Assessment and the CDC Acute Concussion Evaluation tool. Screening tools developed specifically for TBI assessment, such as the Ohio State University TBI ID Method and the Brief Traumatic Brain Injury Questionnaire were found to be seldom used (17% of total participants). Many primary care providers do not feel confident in their ability to diagnose such injuries, often due to lack of expertise in the area, which was reflected in the self-reported survey. As new screening tools become available, it is imperative that they are tested for validity, and then utilized in practice. Due to the complexity of diagnosing traumatic brain injuries, the most simple and accurate screening tools are often the ones preferred by providers. Moving forward, simple new screening tools need to be evaluated for effectiveness and ease of use. These tools should then be introduced to primary care practitioners, with suggestions as to how to best supplement them with other parts of an exam. Since TBIs are becoming an increasingly more common diagnosis in primary care, future advanced nursing evidence-based practice should focus on the recommended screening tools so as to better identify and guide treatment. Future research is needed to evaluate the extent to which part of an exam yield the most pertinent and accurate findings, as well as to compare the effectiveness of screening models utilized in civilian and military settings

Association between 5-Year clinical outcome in patients with nonmedically evacuated mild blast traumatic brain injury and clinical measures collected within 7 days postinjury in combat

Importance: Although previous work has examined clinical outcomes in combat-deployed veterans, questions remain regarding how symptoms evolve or resolve following mild blast traumatic brain injury (TBI) treated in theater and their association with long-term outcomes. Objective: To characterize 5-year outcome in patients with nonmedically evacuated blast concussion compared with combat-deployed controls and understand what clinical measures collected acutely in theater are associated with 5-year outcome. Design, Setting, and Participants: A prospective, longitudinal cohort study including 45 service members with mild blast TBI within 7 days of injury (mean 4 days) and 45 combat deployed nonconcussed controls was carried out. Enrollment occurred in Afghanistan at the point of injury with evaluation of 5-year outcome in the United States. The enrollment occurred from March to September 2012 with 5-year follow up completed from April 2017 to May 2018. Data analysis was completed from June to July 2018. Exposures: Concussive blast TBI. All patients were treated in theater, and none required medical evacuation. Main Outcomes and Measures: Clinical measures collected in theater included measures for concussion symptoms, posttraumatic stress disorder (PTSD) symptoms, depression symptoms, balance performance, combat exposure intensity, cognitive performance, and demographics. Five-year outcome evaluation included measures for global disability, neurobehavioral impairment, PTSD symptoms, depression symptoms, and 10 domains of cognitive function. Forward selection multivariate regression was used to determine predictors of 5-year outcome for global disability, neurobehavior impairment, PTSD, and cognitive function. Results: Nonmedically evacuated patients with concussive blast injury (n = 45; 44 men, mean [SD] age, 31 [5] years) fared poorly at 5-year follow-up compared with combat-deployed controls (n = 45; 35 men; mean [SD] age, 34 [7] years) on global disability, neurobehavioral impairment, and psychiatric symptoms, whereas cognitive changes were unremarkable. Acute predictors of 5-year outcome consistently identified TBI diagnosis with contribution from acute concussion and mental health symptoms and select measures of cognitive performance depending on the model for 5-year global disability (area under the curve following bootstrap validation [AUCBV] = 0.79), neurobehavioral impairment (correlation following bootstrap validation [RBV] = 0.60), PTSD severity (RBV = 0.36), or cognitive performance (RBV = 0.34). Conclusions and Relevance: Service members with concussive blast injuries fared poorly at 5-year outcome. The results support a more focused acute screening of mental health following TBI diagnosis as strong indicators of poor long-term outcome. This extends prior work examining outcome in patients with concussive blast injury to the larger nonmedically evacuated population

Optimising return to work practices following catastrophic injury

This paper aims to enhance understanding of the features of optimal return to work practices following traumatic brain and spinal cord injury and identify barriers and facilitators to their implementation. Executive summary People with catastrophic injuries face many long-term challenges in the community as a result of their injury: one of the most problematic can be in returning to work (RTW). It may not only be a significant issue for the person with a catastrophic injury but also for their family, friends, the employment industry, and society. Worldwide mean RTW rates for people with catastrophic injury are approximately 30-40%; however, in Australia the overall mean rate is unknown. Internationally, the best RTW rates reported for moderate to severe traumatic brain injury (TBI) come from the UK, Sweden and USA, whilst for spinal cord injury (SCI) they are in Switzerland and Sweden. There are several differences in the way rates reported are calculated such as the time post-injury, making it difficult to definitively identify whether one country achieves better RTW rates than another. Several studies have been conducted to determine the factors which facilitate and limit RTW for people with catastrophic injury. These include having pre-injury employment, age, education, severity of injury, level of cognitive impairment, being functionally independent, fatigue, psychological adjustment to the change, social support and the work environment to name a few. There is a general lack of understanding of the experience of people with catastrophic injury who return to work and, therefore, little known about how job retention can be successful in the long-term. Four types of VR interventions have been identified to facilitate RTW – 1) program based rehabilitation, 2) supported employment, 3) case co-ordination and 4) hybrid or mixed. An evidence review identified 15 relevant articles and it was found that there was limited high quality evidence to support any type of intervention more effective than the other. There was however moderate evidence identified for the effectiveness of case co-ordination for achieving successful RTW for people with moderate to severe TBI and high level evidence for a specialist TBI-VR combination intervention. A reduction in the claiming of benefits after 1 year was also observed. The most promising RTW intervention for people with SCI appears to be supported employment; however, as only one RCT has provided this evidence, further studies are required. Several factors that affect the likely success of RTW interventions were also identified in exploring the research evidence and implications for future research were identified. Substantial research has been conducted on RTW interventions in people with TBI since the late 1980s, however this is not the same for SCI. High quality evidence and transparent reporting of study details are still lacking. This NTRI Forum aims to enhance understanding of the features of optimal return to work practices following traumatic brain and spinal cord injury and identify barriers and facilitators to their implementation. Two questions were identified for deliberation in a Stakeholder Dialogue: 1. In the Australian context, what are the barriers to, and facilitators of, application of strategies to optimise RTW outcomes for people with catastrophic injury? 2. How could identified barriers and facilitators be addressed to ensure successful RTW and better retention of people with catastrophic injury? An accompanying document (Dialogue Summary) will present the results of the deliberation upon these question

The contribution of injury severity, executive and implicit functions to awareness of defi cits after traumatic brain injury (TBI)

Deficits in self-awareness are commonly seen after Traumatic Brain Injury (TBI) and adversely affect rehabilitative efforts, independence and quality of life (Ponsford, 2004). Awareness models predict that executive and implicit functions are important cognitive components of awareness though the putative relationship between implicit and awareness processes has not been subject to empirical investigation (Crosson et al., 1989; Ownsworth, Clare, & Morris, 2006; Toglia & Kirk, 2000). Severity of injury, also thought to be a crucial determinant of awareness outcome post-insult, is under-explored in awareness studies (Sherer, Boake, Levin, Silver, Ringholz, & Walter, 1998 ). The present study measured the contribution of injury severity, IQ, mood state, executive and implicit functions to awareness in head-injured patients assigned to moderate/severe head-injured groups using several awareness, executive, and implicit measures. Severe injuries resulted in greater impairments across most awareness, executive and implicit measures compared with moderate injuries, although deficits were still seen in the moderate group. Hierarchical regression results showed that severity of injury, IQ, mood state, executive and implicit functions made signifi cant unique contributions to selective aspects of awareness. Future models of awareness should account for both implicit and executive contributions to awareness and the possibility that both are vulnerable to disruption after neuropathology. ( JINS , 2010, 16 , 1– 10 .

Investigating the 'latent' deficit hypothesis : age at time of head injury, executive and implicit functions and behavioral insight

This study investigated the 'latent deficit' hypothesis in two groups of frontotemporal headinjured patients, those injured prior to steep morphological and corresponding functional maturational periods for frontotemporal networks (≤ age 25), and those injured >28 years. The latent deficit hypothesis proposes that early injuries produce enduring cognitive deficits manifest later in the lifespan with graver consequences for behavior than adult injuries, particularly after frontal pathology (Eslinger, Grattan, Damasio & Damasio, 1992). Implicit and executive deficits both contribute to behavioral insight after frontotemporal head injury (Barker, Andrade, Romanowski, Morton & Wasti, 2006). On the basis of morphological and behavioral data, we hypothesised that early injury would confer greater vulnerability to impairment on tasks associated with frontotemporal regions than later injury. Patients completed experimental tasks of implicit cognition, executive function measures and the DEX measure of behavioural insight (Behavioral Assessment of the Dysexecutive Syndrome: Wilson, Alderman, Burgess, Emslie, & Evans, 1996). The Early Injury group were more impaired on implicit cognition tasks compared to controls that Late Injury patients. There were no marked group differences on most executive function measures. Executive ability only contributed to behavioral awareness in the Early Injury Group. Findings showed that age at injury moderates the relationship between executive and implicit cognition and behavioral insight and that early injuries result in longstanding deficits to functions associated with frontotemporal regions partially supporting the latent deficit hypothesis

Neuropsychological functioning in a national cohort of severe traumatic brain injury: demographic and acute injury-related predictors

Objectives: To determine the rates of cognitive impairment 1 year after severe traumatic brain injury (TBI) and to examine the influence of demographic, injury severity, rehabilitation, and subacute functional outcomes on cognitive outcomes 1 year after severe TBI. Setting: National multicenter cohort study over 2 years. Participants: Patients (N = 105), aged 16 years or older, with Glasgow Coma Scale score of 3 to 8 and Galveston Orientation and Amnesia Test score of more than 75. Main Measures : Neuropsychological tests representing cognitive domains of Executive Functions, Processing Speed, and Memory. Injury severity included Rotterdam computed tomography score, Glasgow Coma Scale score, and posttraumatic amnesia (PTA) duration, together with length of rehabilitation and Glasgow Outcome Scale–Extended score. Results: In total, 67% of patients with severe TBI had cognitive impairment. Executive Functions, Processing Speed, and Memory were impaired in 41%, 58%, and 57% of patients, respectively. Using multiple regression analysis, Processing Speed was significantly related to PTA duration, Glasgow Outcome Scale–Extended score, and length of inpatient rehabilitation (R 2 = 0.30); Memory was significantly related to Glasgow Outcome Scale–Extended score (R 2 = 0.15); and Executive Functions to PTA duration (R 2 = 0.10). Rotterdam computed tomography and Glasgow Coma Scale scores were not associated with cognitive functioning at 1 year postinjury. Conclusion: Findings highlight cognitive consequences of severe TBI, with nearly two-thirds of patients showing cognitive impairments in at least 1 of 3 cognitive domains. Regarding injury severity predictors, only PTA duration was related to cognitive functioning.acceptedVersio

Disrupted White Matter Microstructure of the Cerebellar Peduncles in Scholastic Athletes After Concussion.

Concussion, or mild traumatic brain injury (mTBI), is a major public health concern, linked with persistent post-concussive syndrome, and chronic traumatic encephalopathy. At present, standard clinical imaging fails to reliably detect traumatic axonal injury associated with concussion and post-concussive symptoms. Diffusion tensor imaging (DTI) is an MR imaging technique that is sensitive to changes in white matter microstructure. Prior studies using DTI did not jointly investigate white matter microstructure in athletes, a population at high risk for concussive and subconcussive head traumas, with those in typical emergency room (ER) patients. In this study, we determine DTI scalar metrics in both ER patients and scholastic athletes who suffered concussions and compared them to those in age-matched healthy controls. In the early subacute post-concussion period, athletes demonstrated an elevated rate of regional decreases in axial diffusivity (AD) compared to controls. These regional decreases of AD were especially pronounced in the cerebellar peduncles, and were more frequent in athletes compared to the ER patient sample. The group differences may indicate differences in the mechanisms of the concussive impacts as well as possible compound effects of cumulative subconcussive impacts in athletes. The prevalence of white matter abnormality in cerebellar tracts lends credence to the hypothesis that post-concussive symptoms are caused by shearing of axons within an attention network mediated by the cerebellum, and warrant further study of the correlation between cerebellar DTI findings and clinical, neurocognitive, oculomotor, and vestibular outcomes in mTBI patients