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Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder associated with exposure to head trauma. In 2015, a panel of neuropathologists funded by the NINDS/NIBIB defined preliminary consensus neuropathological criteria for CTE, including the pathognomonic lesion of CTE as "an accumulation of abnormal hyperphosphorylated tau (p-tau) in neurons and astroglia distributed around small blood vessels at the depths of cortical sulci and in an irregular pattern," based on review of 25 tauopathy cases. In 2016, the consensus panel met again to review and refine the preliminary criteria, with consideration around the minimum threshold for diagnosis and the reproducibility of a proposed pathological staging scheme. Eight neuropathologists evaluated 27 cases of tauopathies (17 CTE cases), blinded to clinical and demographic information. Generalized estimating equation analyses showed a statistically significant association between the raters and CTE diagnosis for both the blinded (OR = 72.11, 95% CI = 19.5-267.0) and unblinded rounds (OR = 256.91, 95% CI = 63.6-1558.6). Based on the challenges in assigning CTE stage, the panel proposed a working protocol including a minimum threshold for CTE diagnosis and an algorithm for the assessment of CTE severity as "Low CTE" or "High CTE" for use in future clinical, pathological, and molecular studies.

The objective of this study was to examine the benefits of long-term inpatient rehabilitation for individuals with moderate-to-severe traumatic brain injuries (TBIs).Retrospective database review of 67 individuals with moderate-to-severe TBI admitted to a specialised inpatient TBI program. Outcome measures are as follows: (1) functional independence measure + functional assessment measure (FIM+FAM; admission, discharge, change scores); (2) discharge designation (community vs. long-term care (LTC)).There was a mean improvement on FIM+FAM of 54.19 points (SD = 35.63) or 67% between admission and discharge (t(66) = -12.45, p 0.001). Mean time post-injury upon completion of therapy was 409.59 days (SD = 343.93). Upon completion of rehabilitation, 50 (75%) participants were discharged to community and 17 to LTC. Among those returning to community, those with longer length of stays were more severely disabled on admission (t(35.9) = -4.86, p 0.001). Controlling for admission functional status, individuals returning to community following90 days of therapy required a mean of 378.94 days (SD = 298.86) to achieve comparable gains to those less impaired who received shorter periods of rehabilitation (F(1) = 0.530, p = 0.47).Continued specialised inpatient services following acute inpatient rehabilitation for individuals with moderate-to-severe TBI can reduce the level of dependency and enhance the likelihood of return to community living.

Purpose: Prostate cancer patients who have undergone androgen deprivation therapy (ADT) may experience cognitive impairment, yet there is an unmet need for nonpharmacological interventions to address cognitive impairment in this population. This study examines the feasibility, acceptability, and preliminary efficacy of a home-based computerized cognitive training (CCT) program to treat cancer-related cognitive impairment. Methods: Sixty men who had received ≥ 3 months of ADT were screened for at least mild cognitive or neurobehavioral impairment and randomized to 8 weeks of CCT or usual care. Follow-up assessments occurred immediately post-intervention or equivalent (T2) and 8 weeks later (T3). The acceptability of CCT was also assessed. Results: Feasibility:A priori feasibility thresholds were partially met (i.e., randomization rate > 50%, retention rate > 70% excluding CCT drop-outs, but < 70% for intent-to-treat). Acceptability: Participants were mostly satisfied with CCT and found it somewhat enjoyable, though barriers to uptake existed. Preliminary efficacy: Linear mixed models indicated significant time by group effects favorable to CCT in reaction time (p =.01), but unfavorable to CCT in verbal and visual memory (ps

BACKGROUND By 2014, all states implemented concussion laws that schools must translate into daily practice; yet, limited knowledge exists regarding implementation of these laws. We examined the extent to which concussion management policies and procedure (P&P) documents of New York State school districts comply with the State's Concussion Awareness and Management Act (the Act). We also aimed to identify barriers to compliance. METHODS Forty-seven school districts provided P&P documents. We examined compliance with the Act and the relationship between compliance and each district's demographics. RESULTS Compliance varied across school districts, with higher overall compliance in large city school districts compared to county districts. However, there was low compliance for several critical items. We found no statistically significant relationship between compliance and demographics. CONCLUSIONS School districts need to increase compliance with concussion legislation to ensure the adequate implementation necessary for the law to impact health and educational outcomes. The results provide important information to individuals charged with the responsibility of implementation and ultimately reducing the negative outcomes associated with brain injuries in schools.

Traumatic brain injury (TBI) is a risk factor for the later development of neurodegenerative diseases that may have various underlying pathologies. Chronic traumatic encephalopathy (CTE) in particular is associated with repetitive mild TBI (mTBI) and is characterized pathologically by aggregation of hyperphosphorylated tau into neurofibrillary tangles (NFTs). CTE may be suspected when behavior, cognition, and/or memory deteriorate following repetitive mTBI. Exposure to blast overpressure from improvised explosive devices (IEDs) has been implicated as a potential antecedent for CTE amongst Iraq and Afghanistan Warfighters. In this study, we identified biomarker signatures in rats exposed to repetitive low-level blast that develop chronic anxiety-related traits and in human veterans exposed to IED blasts in theater with behavioral, cognitive, and/or memory complaints. Rats exposed to repetitive low-level blasts accumulated abnormal hyperphosphorylated tau in neuronal perikarya and perivascular astroglial processes. Using positron emission tomography (PET) and the [18F]AV1451 (flortaucipir) tau ligand, we found that five of 10 veterans exhibited excessive retention of [18F]AV1451 at the white/gray matter junction in frontal, parietal, and temporal brain regions, a typical localization of CTE tauopathy. We also observed elevated levels of neurofilament light (NfL) chain protein in the plasma of veterans displaying excess [18F]AV1451 retention. These findings suggest an association linking blast injury, tauopathy, and neuronal injury. Further study is required to determine whether clinical, neuroimaging, and/or fluid biomarker signatures can improve the diagnosis of long-term neuropsychiatric sequelae of mTBI.

The relationship between blood alcohol level (BAL) and mild traumatic brain injury (mTBI) remains in need of improved characterization. Adult patients suffering mTBI without intracranial pathology on computed tomography (CT) from the prospective Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot study with emergency department (ED) Glasgow Coma Scale (GCS) 13-15 and recorded blood alcohol level (BAL) were extracted. BAL≥80-mg/dl was set as proxy for excessive use. Multivariable regression was performed for patients with six-month Glasgow Outcome Scale-Extended (GOSE; functional recovery) and Wechsler Adult Intelligence Scale Processing Speed Index Composite Score (WAIS-PSI; nonverbal processing speed), using BAL≥80-mg/dl and80-mg/dl cohorts, adjusting for demographic/injury factors. Overall, 107 patients were aged 42.7±16.8-years, 67.3%-male, and 80.4%-Caucasian; 65.4% had BAL=0-mg/dl, 4.6% BAL80-mg/dl, and 30.0% BAL≥80-mg/dl (range 100-440-mg/dl). BAL differed across loss of consciousness (LOC; none: median 0-mg/dl [interquartile range (IQR) 0-0],30-min: 0-mg/dl [0-43], ≥30-min: 224-mg/dl [50-269], unknown: 108-mg/dl [0-232]; p=0.002). GCS15 associated with higher BAL (19-mg/dl [0-204] vs. 0-mg/dl [0-20]; p=0.013). On univariate analysis, BAL≥80-mg/dl associated with less-than-full functional recovery (GOSE≤7; 38.1% vs. 11.5%; p=0.025) and lower WAIS-PSI (92.4±12.7, 30th-percentile vs. 105.1±11.7, 63rd-percentile; p0.001). On multivariable regression BAL≥80-mg/dl demonstrated an odds ratio of 8.05 (95% CI [1.35-47.92]; p=0.022) for GOSE≤7 and an adjusted mean decrease of 8.88-points (95% CI [0.67-17.09]; p=0.035) on WAIS-PSI. Day-of-injury BAL80-mg/dl after uncomplicated mTBI was associated with decreased GCS score and prolongation of reported LOC. BAL may be a biomarker for impaired return to baseline function and decreased nonverbal processing speed at six-months postinjury. Future confirmatory studies are needed.

Traumatic brain injury (TBI) often leads to heterogeneous clinical outcomes, which may be influenced by genetic variation. A single-nucleotide polymorphism (SNP) in the dopamine D2 receptor (DRD2) may influence cognitive deficits following TBI. However, part of the association with DRD2 has been attributed to genetic variability within the adjacent ankyrin repeat and kinase domain containing 1 protein (ANKK1). Here, we utilize the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study to investigate whether a novel DRD2 C957T polymorphism (rs6277) influences outcome on a cognitive battery at 6 months following TBI—California Verbal Learning Test (CVLT-II), Wechsler Adult Intelligence Test Processing Speed Index Composite Score (WAIS-PSI), and Trail Making Test (TMT). Results in 128 Caucasian subjects show that the rs6277 T-allele associates with better verbal learning and recall on CVLT-II Trials 1–5 (T-allele carrier 52.8 ± 1.3 points, C/C 47.9 ± 1.7 points; mean increase 4.9 points, 95% confidence interval [0.9 to 8.8]; p = 0.018), Short-Delay Free Recall (T-carrier 10.9 ± 0.4 points, C/C 9.7 ± 0.5 points; mean increase 1.2 points [0.1 to 2.5]; p = 0.046), and Long-Delay Free Recall (T-carrier 11.5 ± 0.4 points, C/C 10.2 ± 0.5 points; mean increase 1.3 points [0.1 to 2.5]; p = 0.041) after adjusting for age, education years, Glasgow Coma Scale, presence of acute intracranial pathology on head computed tomography scan, and genotype of the ANKK1 SNP rs1800497 using multivariable regression. No association was found between DRD2 C947T and non-verbal processing speed (WAIS-PSI) or mental flexibility (TMT) at 6 months. Hence, DRD2 C947T (rs6277) may be associated with better performance on select cognitive domains independent of ANKK1 following TBI.

Importance Mild traumatic brain injury (mTBI), or concussion, in children is a rapidly growing public health concern because epidemiologic data indicate a marked increase in the number of emergency department visits for mTBI over the past decade. However, no evidence-based clinical guidelines have been developed to date for diagnosing and managing pediatric mTBI in the United States. Objective To provide a guideline based on a previous systematic review of the literature to obtain and assess evidence toward developing clinical recommendations for health care professionals related to the diagnosis, prognosis, and management/treatment of pediatric mTBI. Evidence Review The Centers for Disease Control and Prevention (CDC) National Center for Injury Prevention and Control Board of Scientific Counselors, a federal advisory committee, established the Pediatric Mild Traumatic Brain Injury Guideline Workgroup. The workgroup drafted recommendations based on the evidence that was obtained and assessed within the systematic review, as well as related evidence, scientific principles, and expert inference. This information includes selected studies published since the evidence review was conducted that were deemed by the workgroup to be relevant to the recommendations. The dates of the initial literature search were January 1, 1990, to November 30, 2012, and the dates of the updated literature search were December 1, 2012, to July 31, 2015. Findings The CDC guideline includes 19 sets of recommendations on the diagnosis, prognosis, and management/treatment of pediatric mTBI that were assigned a level of obligation (ie, must, should, or may) based on confidence in the evidence. Recommendations address imaging, symptom scales, cognitive testing, and standardized assessment for diagnosis; history and risk factor assessment, monitoring, and counseling for prognosis; and patient/family education, rest, support, return to school, and symptom management for treatment. Conclusions and Relevance This guideline identifies the best practices for mTBI based on the current evidence; updates should be made as the body of evidence grows. In addition to the development of the guideline, CDC has created user-friendly guideline implementation materials that are concise and actionable. Evaluation of the guideline and implementation materials is crucial in understanding the influence of the recommendations.

Epidemiological studies suggest that a single moderate-to-severe traumatic brain injury (TBI) is associated with an increased risk of neurodegenerative disease, including Alzheimer's disease (AD) and Parkinson's disease (PD). Histopathological studies describe complex neurodegenerative pathologies in individuals exposed to single moderate-to-severe TBI or repetitive mild TBI, including chronic traumatic encephalopathy (CTE). However, the clinicopathological links between TBI and post-traumatic neurodegenerative diseases such as AD, PD, and CTE remain poorly understood. Here, we describe the methodology of the Late Effects of TBI (LETBI) study, whose goals are to characterize chronic post-traumatic neuropathology and to identify in vivo biomarkers of post-traumatic neurodegeneration. LETBI participants undergo extensive clinical evaluation using National Institutes of Health TBI Common Data Elements, proteomic and genomic analysis, structural and functional magnetic resonance imaging (MRI), and prospective consent for brain donation. Selected brain specimens undergo ultra-high resolution ex vivo MRI and histopathological evaluation including whole–mount analysis. Co-registration of ex vivo and in vivo MRI data enables identification of ex vivo lesions that were present during life. In vivo signatures of postmortem pathology are then correlated with cognitive and behavioral data to characterize the clinical phenotype(s) associated with pathological brain lesions. We illustrate the study methods and demonstrate proof of concept for this approach by reporting results from the first LETBI participant, who despite the presence of multiple in vivo and ex vivo pathoanatomic lesions had normal cognition and was functionally independent until her mid-80s. The LETBI project represents a multidisciplinary effort to characterize post-traumatic neuropathology and identify in vivo signatures of postmortem pathology in a prospective study.

Long-term follow-up studies conducted during the K–12 school years suggest that challenges related to childhood traumatic brain injury (TBI) tend to persist or worsen over time. A 1999 survey of State Directors of Special Education revealed that most states had emerging initiatives for children with TBI and were expanding their capacity to serve this growing population. To determine whether significant changes in patterns of identification and service delivery had occurred, State Directors and brain injury consumer organizations were surveyed. Survey results show some improvement, but significant gaps remain. Most state education administrators perceive a gap between incidence of childhood TBI and identification of students with TBI to receive special education services. Recommendations for policy changes and research are provided.

To characterize sleep architecture and self-reported sleep quality, fatigue and daytime sleepiness in individuals with TBI. Possible relationships between sleep architecture and self-reported sleep quality, fatigue and daytime sleepiness were examined.Forty-four community-dwelling adults with TBI completed the Pittsburgh Sleep Quality Index (PSQI), Multidimensional Assessment of Fatigue (MAF) and Epworth Sleepiness Scale (ESS). They underwent two nights of in-laboratory nocturnal polysomnography (NPSG). Pearson product-moment correlation coefficients and hierarchical linear regression was used to analyse the data.Based on the PSQI cut-off score of ≥ 10, 22 participants were characterized as poor sleepers. Twenty-seven participants met criteria for clinically significant fatigue as measured by the GFI of the MAF. Fourteen participants met criteria for excessive daytime sleepiness as measured by the ESS. Poor sleep quality was associated with poor sleep efficiency, short duration of stage 2 sleep and long duration of rapid eye movement sleep. There was little-to-no association between high levels of fatigue or daytime sleepiness with NPSG sleep parameters.A high proportion of the sample endorsed poor sleep quality, fatigue and daytime sleepiness. Those who reported poorer sleep quality evidenced a shorter proportion of time spent in stage 2 sleep. These findings suggest that disruptions in stage 2 sleep might underlie the symptoms of sleep disturbance experienced following TBI.

The Center for Medicare and Medicaid Innovation under the Centers for Medicare and Medicaid Services has invited institutions to demonstrate ways to bundle services into a 90-day episode of acute care that will lower costs and hospital re-admission rates. While these goals are laudable, they overlook the need for and value attained in postacute treatment. This article argues for elimination of the diagnosis of stroke from the proposed demonstration project due to misaligned financial incentives that will severely compromise patient outcomes.

Objective: To investigate the clinical management and medical follow-up of patients with mild traumatic brain injury (mTBI) presenting to emergency departments (EDs). Methods: Overall, 168 adult patients with mTBI from the prospective, multicentre Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) Pilot study with Glasgow Coma Scale (GCS) 13–15, no polytrauma and alive at six months were included. Predictors for hospital admission, three-month follow-up referral and six-month functional disability (Glasgow Outcome Scale-Extended (GOSE) ≤ 6) were analysed using multivariable regression. Results: Overall, 48% were admitted to hospital, 22% received three-month referral and 27% reported six-month functional disability. Intracranial pathology on ED head computed tomography (multivariable odds ratio (OR) = 81.08, 95% confidence interval (CI) [10.28–639.36]) and amnesia (>30-minutes: OR = 5.27 [1.75–15.87]; unknown duration: OR = 4.43 [1.26–15.62]) predicted hospital admission. Older age (per-year OR = 1.03 [1.01–1.05]) predicted three-month referral, while part-time/unemployment predicted lack of referral (OR = 0.17 [0.06–0.50]). GCS < 15 (OR = 2.46 [1.05–5.78]) and prior history of seizures (OR = 3.62 [1.21–10.89]) predicted six-month functional disability, while increased education (per-year OR = 0.86 [0.76–0.97]) was protective. Conclusions: Clinical factors modulate triage to admission, while demographic/socioeconomic elements modulate follow-up care acquisition; six-month functional disability associates with both clinical and demographic/socioeconomic variables. Improving triage to acute and outpatient care requires further investigation to optimize resource allocation and outcome after mTBI. ClinicalTrials.gov registration: NCT01565551

Objective Preliminary evaluation of the efficacy of a Web-based group intervention (Online EmReg) to improve emotion regulation (ER) in individuals with traumatic brain injury (TBI). Design Pre-/post-within-subject design with baseline, end-of-treatment, and 12-week follow-up assessments. Participants Ninety-one individuals with TBI and deficits in ER. Intervention Twenty-four sessions of training in ER skills delivered by group videoconference. Measures Difficulties in Emotion Regulation Scale (DERS), Positive Affect Negative Affect Schedule (PANAS), Satisfaction With Life Scale (SWLS), Problem Solving Inventory (PSI), Social Problem Solving Inventory-Revised: Short Form (SPSI-R:S), and Dysexecutive Questionnaire (DEX). Results Significant changes with large effect sizes were found for the DERS at the 12-week follow-up assessment. Significant and moderate changes were found on the SWLS, DEX, PSI, and subscales of the PANAS and SPSI-R:S. Conclusions Online EmReg appears to be a promising method of delivering a group intervention to improve ER following TBI.

Statement of purpose This symposium will highlight innovative methods used in TBI research and interventions, and discuss needed advancement in the field over the next decade. Topic description/Audience engagement TBI is a complex medical and public health issue, one that requires more consistent and collective conversations surrounding targeted efforts. This symposium will provide a platform for discussion of lessons learned from recent, innovative TBI research and will engage the audience in conversations concerning where clinical and non-clinical practitioners and researchers should be headed. As part of the conversation, researchers from Injury Control Research Centres (ICRCs) will elicit interactive discussions and practical steps for change within the next decade of TBI research. Speaker descriptions: 1.) Ecologic Momentary Assessment use among Youth post-TBI –Douglas Wiebe, Kit Delgado, Christina Master. Physical and cognitive rest are recommended as the cornerstone of treatment for concussion, largely based on expert opinion. However, it is unclear whether physical and cognitive rest aid recovery in youth with a concussion. We have developed a protocol that uses ecologic momentary assessment to follow youth for 4 weeks after they sustain a concussion, to gather real-time reports of cognitive and physical activity and real-time symptom reports. We developed an electronic platform that enrols concussion patients from paediatric and adult emergency departments and sports medicine clinics. This presentation will discuss the role of physical and cognitive rest and activity in recovery from concussion, the electronic platform, and how its real-time updates can be used by physicians and in clinical trials of therapies for concussion. 2.) Concussion Reporting among Collegiate Athletes and Academy Cadets –Paula Gildner, Johna Register. This presentation will discuss a theory driven data collection instrument, that was used to establish baseline normative characteristics, knowledge, intentions, and attitudes and beliefs associated with concussion reporting and symptom disclosure among collegiate, student-athletes and service academy cadets. We will also discuss the development of and preliminary data from an intervention program, based on the aforementioned instrument, which aimed to improve concussion-related normative perceptions, knowledge, attitudes, beliefs and behaviours among these emerging adults. The efficacy and implementation of the intervention will be discussed. 3.) Examining TBI Research Methods The Intersection of Injury prevention, Neuroscience, Medicine, and Public Policy –Wayne Gordon. Traumatic Brain Injury (TBI) is a cross-cutting injury and disease that intersects with neuroscience, injury prevention and control, medicine, and public policy. While over the past decade there have been significant financial resources and energy invested into TBI research, there is much to be learned. This presentation will discuss major areas of TBI research that require in depth exploration. For example, we know little about: the cascade of events that occur after the brain is injured; TBI as a chronic health condition, the long-term effects of concussion (sports and non-sports related) in youth; reducing TBI as a risk factor for social failure in terms of violence, substance abuse, homelessness and suicidality, and the policy issues that impact the adoption of validated approaches to screening for TBI and the provision of needed interventions.

We report the clinical, neuroimaging, and neuropathologic characteristics of 2 patients who developed early onset dementia after a moderate-severe traumatic brain injury (TBI). Neuropathological evaluation revealed abundant β-amyloid neuritic and cored plaques, diffuse β-amyloid plaques, and frequent hyperphosphorylated-tau neurofibrillary tangles (NFT) involving much of the cortex, including insula and mammillary bodies in both cases. Case 1 additionally showed NFTs in both the superficial and deep cortical layers, occasional perivascular and depth-of-sulci NFTs, and parietal white matter rarefaction, which corresponded with decreased parietal fiber tracts observed on ex vivo MRI. Case 2 additionally showed NFT predominance in the superficial layers of the cortex, hypothalamus and brainstem, diffuse Lewy bodies in the cortex, amygdala and brainstem, and intraneuronal TDP-43 inclusions. The neuropathologic diagnoses were atypical Alzheimer disease (AD) with features of chronic traumatic encephalopathy and white matter loss (Case 1), and atypical AD, dementia with Lewy bodies and coexistent TDP-43 pathology (Case 2). These findings support an epidemiological association between TBI and dementia and further characterize the variety of misfolded proteins that may accumulate after TBI. Analyses with comprehensive clinical, imaging, genetic, and neuropathological data are required to characterize the full clinicopathological spectrum associated with dementias occurring after moderate-severe TBI.

Objective To determine the efficacy of 2 different interventions (cognitive behavioral therapy [CBT] and supportive psychotherapy [SPT]) to treat post-traumatic brain injury (TBI) depression. Participants A sample of 77 community-dwelling individuals with a TBI, and a diagnosis of depression. Participants were randomized into treatment conditions either CBT or SPT and received up to 16 sessions of individual psychotherapy. Measures Participants completed the Structured Clinical Interview for DSM-IV and self-report measures of depression (Beck Depression Inventory-Second Edition), anxiety (State-Trait Anxiety Inventory), perceived social support (Interpersonal Support Evaluation List), stressful life events (Life Experiences Survey), and quality of life (QOL) before beginning and immediately following treatment. Results No significant differences were found at baseline between CBT and SPT groups on demographic factors (sex, age, education, race, and time since injury) or baseline measures of depression, anxiety, participation, perceived social support, stressful life events, or QOL. Analyses of variance revealed significant time effects for the Beck Depression Inventory-Second Edition, State-Trait Anxiety Inventory, and QOL outcome measures but no group effects. Intention-to-treat mixed effects analyses did not find any significant difference in patterns of scores of the outcome measures between the CBT and SPT intervention groups. Conclusions Both forms of psychotherapy were efficacious in improving diagnoses of depression and anxiety and reducing depressive symptoms. These findings suggest that in this sample of individuals with TBI, CBT was not more effective in treating depression than SPT, though further research is needed with larger sample sizes to identify different components of these interventions that may be effective with different TBI populations. ClinicalTrials.gov Identifier: NCT00211835.

Objective To provide an overview of a series of projects that used a structured self-report screening tool in diverse settings and samples to screen for lifetime history of traumatic brain injury (TBI). Setting Diverse community settings. Participants Homeless persons (n = 111), individuals with HIV seeking vocational rehabilitation (n = 173), youth in the juvenile justice system (n = 271), public schoolchildren (n = 174), substance users (n = 845), intercollegiate athletes (n = 90), and other community-based samples (n = 396). Design Cross-sectional. Main measure Brain Injury Screening Questionnaire. Results Screening using the Brain Injury Screening Questionnaire finds that 27% to 54% of those in high-risk populations report a history of TBI with chronic symptoms. Associations between TBI and social, academic, or other problems are evident in several studies. In non-high-risk community samples, 9% to 12% of individuals report TBI with chronic symptoms. Conclusion Systematic TBI screening can be implemented efficiently and inexpensively in a variety of settings. Lifetime TBI history data gathered using a structured self-report instrument can augment existing estimates of the prevalence of TBI, both as an acute event and as a chronic condition. Identification of individuals with TBI can facilitate primary prevention efforts, such as reducing risk for reinjury in high-risk groups, and provide access to appropriate interventions that can reduce the personal and societal costs of TBI (tertiary prevention).

BACKGROUND: Obstructive sleep apnea (OSA) is commonly found in individuals with traumatic brain injury (TBI) and may exacerbate TBI-related symptoms. Nocturnal polysomnography (NPSG) is considered the gold standard for detecting the presence of sleep apnea. However, there is a limitation with its use known as the “first-night effect” (aberrant polysomnography findings on the first night in a sleep lab). OBJECTIVE: The primary objectives were to investigate the night-to-night consistency of diagnosing and classifying obstructive sleep apnea in individuals with TBI, and ascertain if individuals with TBI are prone to a first-night effect. METHODS: 47 community-dwelling adults with self-reported mild-to-severe TBI underwent two nights of in-laboratory NPSG to examine variability between the first and second night with regards to OSA diagnosis and severity as well as sleep architecture. RESULTS: OSA detection and severity were consistent from night-to-night in 89% of participants with TBI. Participants with TBI demonstrated longer REM latency on the first night compared to the second night of sleep study. CONCLUSIONS: These findings indicate that two nights of in-laboratory NPSG are generally consistent in reliably diagnosing OSA in individuals with TBI and that first-night effects are minimal. One night of NPSG has diagnostic utility in the evaluation of sleep disorders in individuals with TBI.

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.

Objective: Mild traumatic brain injury (mTBI) patients are frequently admitted to high levels of care despite limited evidence suggesting benefit. Such decisions may contribute to the significant cost of caring for mTBI patients. Understanding the factors that drive disposition decision making and how disposition is associated with outcomes is necessary for developing an evidence-base supporting disposition decisions. We evaluated factors associated with emergency department triage of mTBI patients to 1 of 3 levels of care: home, inpatient floor, or intensive care unit (ICU). Methods: This multicenter, prospective, cohort study included patients with isolated head trauma, a cranial computed tomography as part of routine care, and a Glasgow Coma Scale (GCS) score of 13 to 15. Data analysis was performed using multinomial logistic regression. Results: Of the 304 patients included, 167 (55%) were discharged home, 76 (25%) were admitted to the inpatient floor, and 61 (20%) were admitted to the ICU. In the multivariable model, admission to the ICU, compared with floor admission, varied by study site, odds ratio (OR) 0.18 (95% confidence interval [CI], 0.06-0.57); antiplatelet/anticoagulation therapy, OR 7.46 (95% CI, 1.79-31.13); skull fracture, OR 7.60 (95% CI, 2.44-23.73); and lower GCS, OR 2.36 (95% CI, 1.05-5.30). No difference in outcome was observed between the 3 levels of care. Conclusion: Clinical characteristics and local practice patterns contribute to mTBI disposition decisions. Level of care was not associated with outcomes. Intracranial hemorrhage, GCS 13 to 14, skull fracture, and current antiplatelet/anticoagulant therapy influenced disposition decisions. (C) 2014 Elsevier Inc. All rights reserved.

Biomarkers are important for accurate diagnosis of complex disorders such as traumatic brain injury (TBI). For a complex and multifaceted condition such as TBI, it is likely that a single biomarker will not reflect the full spectrum of the response of brain tissue to injury. Ubiquitin C-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) are among of the most widely studied biomarkers for TBI. Because UCH-L1 and GFAP measure distinct molecular events, we hypothesized that analysis of both biomarkers would be superior to analysis of each alone for the diagnosis and prognosis of TBI. Serum levels of UCH-L1 and GFAP were measured in a cohort of 206 patients with TBI enrolled in a multicenter observational study (Transforming Research and Clinical Knowledge in Traumatic Brain Injury [TRACK-TBI]). Levels of the two biomarkers were weakly correlated to each other (r=0.364). Each biomarker in isolation had good sensitivity and sensitivity for discriminating between TBI patients and healthy controls (area under the curve [AUC] 0.87 and 0.91 for UCH-L1 and GFAP, respectively). When biomarkers were combined, superior sensitivity and specificity for diagnosing TBI was obtained (AUC 0.94). Both biomarkers discriminated between TBI patients with intracranial lesions on CT scan and those without such lesions, but GFAP measures were significantly more sensitive and specific (AUC 0.88 vs. 0.71 for UCH-L1). For association with outcome 3 months after injury, neither biomarker had adequate sensitivity and specificity (AUC 0.65-0.74, for GFAP, and 0.59-0.80 for UCH-L1, depending upon Glasgow Outcome Scale Extended [GOS-E] threshold used). Our results support a role for multiple biomarker measurements in TBI research. (ClinicalTrials.gov Identifier NCT01565551)

Aims: This study aimed to examine the differential treatment effects of cognitive–behavioral therapy (CBT) and supportive psychotherapy (SPT) on self-reported symptoms of depression in individuals with traumatic brain injury (TBI) who sought treatment for major depressive disorder (MDD). Methods: Participants were individuals with a documented TBI meeting criteria for MDD who, as part of a larger randomized controlled trial comparing treatments for MDD after TBI, received CBT (n = 22) or SPT (n = 22). The average age of participants was 48.8 years (standard deviation = 10.2), 57.1% were female, 57.5% were Caucasian, 20% were Hispanic and 15% were African–American. The main outcome measure was the Beck Depression Inventory-‘II (BDI-II). Results: Mean total BDI-‘II score for all participants combined at baseline was 25 (standard deviation = 10.0). There were no significant differences in total BDI-‘II score between treatment groups at either baselineor at the end of treatment. Participants treated with CBT reported significant improvements in sadness, loss of interest and loss of interest in sex, while participants treated with SPT reported significant improvements in symptoms of agitation and irritability. Conclusion: SPT may better target symptoms of behavioral disinhibition (agitation and irritability), while CBT may better target mood symptoms (sadness) and their behavioral manifestations (loss of interest and loss of interest in sex).

Deficits in attention, processing speed and executive functioning are among the most commonly reported and functionally limiting cognitive impairments among individuals with TBI. Changes in mood can exacerbate cognitive deficits and reduce life quality. Contemporary hierarchical models of cognitive functioning suggest that attention/arousal processes underlie and support higher-order functions. Building on decades of clinical research, a synergistic, integrative approach to neurorehabilitation is described, which combines bottom-up and top-town cognitive interventions in addition to psychotherapeutic interventions for mood. This approach is intended to address directly impairments in both foundational (i.e., attention) and higher-order (i.e., executive functions) processes. Executive dysfunction is addressed in a top-down fashion through the application of a series of problem-solving and emotional regulation modules that teach and integrate strategies that can be generalised across situations with practice. Attention, arousal and information processing are necessary prerequisites of successful higher-order thinking, attention skills, and are addressed in a bottom-up fashion through intensive individualised attention and processing training tasks. Combining top-down and bottom-up approaches within a comprehensive day-treatment programme can effect a synergistic improvement of overall functioning.

Depression is one of the most common psychiatric diagnoses among individuals with traumatic brain injury (TBI). Prevalence of post-TBI depression (PTBID) ranges from 12 to 60% and is generally higher than rates reported in the general population. The wide range in reported rates is attributed to methodological variability across studies, including measurement and sampling differences. Several systematic reviews have been published in the past 5 years, reporting on outcomes for depression across different classes of interventions, including pharmacological, biomedical and behavioural. The consensus across reviews is that more research is necessary to develop evidence-based practice guidelines. The present narrative review synthesises the findings of previous studies, focusing on the nature of the interventions, the eligibility criteria for inclusion and the assessment of outcome. Pharmacological studies are generally more rigorous methodologically, but provide mixed findings. Other biomedical interventions are only at the initial stages of research development, including case and pilot studies. The results of behavioural studies are positive regarding improvements in mood. However, the number of efficacy studies of behavioural interventions for depression is extremely limited. Recommendations for designing interventions are provided.

Brain lesions are subtle or absent in most patients with mild traumatic brain injury (mTBI) and the standard clinical criteria are not reliable for predicting long-term outcome. This study investigates resting-state functional MRI (rsfMRI) to assess semiacute alterations in brain connectivity and its relationship with outcome measures assessed 6 months after injury. Seventy-five mTBI patients were recruited as part of the prospective multicenter Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) pilot study and compared with matched 47 healthy subjects. Patients were classified following radiological criteria: CT/MRI positive, evidence of lesions; CT/MRI negative, without evidence of brain lesions. rsfMRI data were acquired and then processed using probabilistic independent component analysis. We compared the functional connectivity of the resting-state networks (RSNs) between patients and controls, as well as group differences in the interactions between RSNs, and related both to cognitive and behavioral performance at 6 months post-injury. Alterations were found in the spatial maps of the RSNs between mTBI patients and healthy controls in networks involved in behavioral and cognition processes. These alterations were predictive of mTBI patients' outcomes at 6 months post-injury. Moreover, different patterns of reduced network interactions were found between the CT/MRI positive and CT/MRI negative patients and the control group. These rsfMRI results demonstrate that even mTBI patients not showing brain lesions on conventional CT/MRI scans can have alterations of functional connectivity at the semiacute stage that help explain their outcomes. These results suggest rsfMRI as a sensitive biomarker both for early diagnosis and for prediction of the cognitive and behavioral performance of these patients.

Objective To examine the relationship between traumatic brain injury (TBI) and criminal behavior in youth who are incarcerated or on probation in Texas. Setting Seven juvenile justice facilities. Participants Juvenile offenders in state or county correctional facilities or on probation. Design Screening for TBI was conducted among adolescents at 7 juvenile justice centers. Main measures Participants were administered the Brain Injury Screening Questionnaire, and results were linked to participants' offense history and psychiatric diagnoses. Results One in 4 juvenile offenders met criteria for TBI, and the majority of injuries occurred prior to the adolescents' criminal offenses. A history of TBI was related to more violent crimes, as well as more mental health diagnoses and symptoms. Conclusion The high rates of TBI and levels of distress found in juvenile offenders suggest a need for preventive actions, interventions to compensate for challenges related to TBI, and programs to assist individuals' transitions into the community.

BACKGROUND:Traumatic brain injury (TBI) is a complex disorder that is traditionally stratified based on clinical signs and symptoms. Recent imaging and molecular biomarker innovations provide unprecedented opportunities for improved TBI precision medicine, incorporating patho-anatomical and molecular mechanisms. Complete integration of these diverse data for TBI diagnosis and patient stratification remains an unmet challenge. METHODS AND FINDINGS:The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Pilot multicenter study enrolled 586 acute TBI patients and collected diverse common data elements (TBI-CDEs) across the study population, including imaging, genetics, and clinical outcomes. We then applied topology-based data-driven discovery to identify natural subgroups of patients, based on the TBI-CDEs collected. Our hypothesis was two-fold: 1) A machine learning tool known as topological data analysis (TDA) would reveal data-driven patterns in patient outcomes to identify candidate biomarkers of recovery, and 2) TDA-identified biomarkers would significantly predict patient outcome recovery after TBI using more traditional methods of univariate statistical tests. TDA algorithms organized and mapped the data of TBI patients in multidimensional space, identifying a subset of mild TBI patients with a specific multivariate phenotype associated with unfavorable outcome at 3 and 6 months after injury. Further analyses revealed that this patient subset had high rates of post-traumatic stress disorder (PTSD), and enrichment in several distinct genetic polymorphisms associated with cellular responses to stress and DNA damage (PARP1), and in striatal dopamine processing (ANKK1, COMT, DRD2). CONCLUSIONS:TDA identified a unique diagnostic subgroup of patients with unfavorable outcome after mild TBI that were significantly predicted by the presence of specific genetic polymorphisms. Machine learning methods such as TDA may provide a robust method for patient stratification and treatment planning targeting identified biomarkers in future clinical trials in TBI patients. TRIAL REGISTRATION:ClinicalTrials.gov Identifier NCT01565551.

Reliable diagnosis of traumatic brain injury (TBI) is a major public health need. Glial fibrillary acidic protein (GFAP) is expressed in the central nervous system, and breakdown products (GFAP-BDP) are released following parenchymal brain injury. Here, we evaluate the diagnostic accuracy of elevated levels of plasma GFAP-BDP in TBI. Participants were identified as part of the prospective Transforming Research And Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Study. Acute plasma samples (

The idea that multiple traumatic brain injury (TBI) can have a cumulative detrimental effect on functioning is widely accepted. Most research supporting this idea comes from athlete samples, and it is not known whether remote history of previous TBI affects functioning after subsequent TBI in community-based samples. This study investigates whether a previous history of TBI with loss of consciousness (LOC) is associated with worse health and functioning in a sample of individuals who require emergency department care for current TBI. Twenty-three percent of the 586 individuals with current TBI in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury study reported having sustained a previous TBI with LOC. Individuals with previous TBI were more likely to be unemployed ((2)=17.86; p=0.000), report a variety of chronic medical and psychiatric conditions (4.75(2)24.16; p

We described recently a subacute serum autoantibody response toward glial fibrillary acidic protein (GFAP) and its breakdown products 5-10 days after severe traumatic brain injury (TBI). Here, we expanded our anti-GFAP autoantibody (AutoAb[GFAP]) investigation to the multicenter observational study Transforming Research and Clinical Knowledge in TBI Pilot (TRACK-TBI Pilot) to cover the full spectrum of TBI (Glasgow Coma Scale 3-15) by using acute (

OBJECTIVE:: To determine the prevalence of insomnia and posttraumatic brain injury (TBI) fatigue (PTBIF) in individuals with moderate to severe TBI, to explore the relationship between PTBIF and insomnia and their association with outcomes. DESIGN:: Cross-sectional study. SETTING:: Five National Institute of Disability and Rehabilitation Research TBI Model Systems. PARTICIPANTS:: Three hundred thirty-four individuals with TBI who completed 1-year (n = 213) or 2-year (n = 121) follow-up interviews between 2008 and 2012. MAIN OUTCOME RESULTS:: Insomnia occurred in 11% to 24% and PTBIF in 33% to 44% of the individuals. Insomnia and fatigue were both related to sleep disturbance, sleep hygiene, satisfaction with life, anxiety, and depression. PTBIF was associated with greater disability and sleepiness. Insomnia without fatigue was rare (2%-3%) but PTBIF without insomnia occurred in 21% to 23% of the individuals. Comorbidity occurred in 9% to 22% of the individuals. CONCLUSIONS:: Although PTBIF and insomnia are closely related and both associated with poorer quality of life, they are affected independently by a variety of factors, especially psychopathology and sleep quality. A majority of individuals with PTBIF do not have insomnia; and PTBIF appears to be related to disability severity and daytime sleepiness, where insomnia is not. Demographic and injury variables are not strong predictors of insomnia or PTBIF. Language: en

Diffuse axonal injury is a common pathological consequence of Traumatic Brain Injury (TBI). Diffusion Tensor Imaging is an ideal technique to study white matter integrity using the Fractional Anisotropy (FA) index which is a measure of axonal integrity and coherence. There have been several reports showing reduced FA in individuals with TBI, which suggest demyelination or reduced fiber density in white matter tracts secondary to injury. Individuals with TBI are usually diagnosed with cognitive deficits such as reduced attention span, memory and executive function. In this study we sought to investigate correlations between brain functional networks, white matter integrity, and TBI severity in individuals with TBI ranging from mild to severe. A resting state functional magnetic resonance imaging protocol was used to study the default mode network in subjects at rest. FA values were decreased throughout all white matter tracts in the mild to severe TBI subjects. FA values were also negatively correlated with TBI injury severity ratings. The default mode network showed several brain regions in which connectivity measures were higher among individuals with TBI relative to control subjects. These findings suggest that, subsequent to TBI, the brain may undergo adaptation responses at the cellular level to compensate for functional impairment due to axonal injury.

Comparing results across studies in traumatic brain injury (TB!) has been difficult because of the variability in data coding, definitions, and collection procedures. The global aim of the Working Group on Demographics and Clinical Assessment was to develop recommendations on the coding of clinical and demographic variables for TBI studies applicable across the broad spectrum of TBI, and to classify these as core, supplemental, or emerging. The process was consensus driven, with input from experts over a broad range of disciplines. Special consideration was given to military and pediatric TBI. Categorizing clinical elements as core versus supplemental proved difficult, given the great variation in types of studies and their interests. The data elements are contained in modules, which are grouped together in categories. Three levels of detail for coding data elements were developed: basic, intermediate, and advanced, with the greatest level of detail in the advanced version. In every case, the more detailed coding can be collapsed into the basic version. Templates were produced to summarize coding formats, motivation of choices, and recommendations for procedures. Work is ongoing to include more international participation and to provide an electronic data entry format with pull-down menus and automated data checks. This proposed standardization will facilitate comparison of research findings across studies and encourage high-quality meta-analysis of individual patient data.

Gordon WA. Perspectives on rehabilitation research. The author provides his perspectives on both the methodologic and funding challenges faced by rehabilitation researchers. His concerns are conveyed about the devaluing of rehabilitation research by federal funding agencies and Congress.

While there has been considerable research on the patterns of pre- and post-substance use among individuals with traumatic brain injury (TBI), little is known about the incidence of co-morbidity between TBI and substance abuse (SA) in individuals whose primary disorder is SA. In the current study, the prevalence of co-occurring TBI in individuals seeking treatment for SA was examined. A total of 845 individuals seeking treatment for SA in New York State were screened via the Brain Injury Screening Questionnaire for the presence of a co-morbid TBI. Results indicate that more than 50% of the sample had results that were positive for a TBI. On average, individuals reported a mean of 6 ± 8 blows to the head, with the number ranging from 0 to 57 and the average age of the first TBI being 14.5 years. Results indicate a high level of co-morbidity between TBI and SA and the need for routine screening for TBI in this population.

Hanks RA, Millis SR, Ricker JH, Giacino JT, Nakese-Richardson R, Frol AB, Novack TA, Kalmar K, Sherer M, Gordon WA. The predictive validity of a brief inpatient neuropsychologic battery for persons with traumatic brain injury. Objective To examine the predictive validity of a brief neuropsychologic test battery consisting of the Galveston Orientation and Amnesia Test, the California Verbal Learning Test–II, Trail-Making Test (TMT), Symbol Digit Modalities Test, grooved pegboard, phonemic and categorical word generation tasks, the Wechsler Test of Adult Reading (WTAR), and the Wisconsin Card Sorting Test–64 relative to functional outcome at 1 year in persons with traumatic brain injury. Design Inception cohort study. Follow-up period of 12 months. Setting Seven Traumatic Brain Injury Model System centers. Neuropsychologic testing was conducted during the acute inpatient rehabilitation stay and functional outcome measures were obtained at 1-year outpatient follow-up. Participants Adults (N=174) who met criteria for admission to inpatient brain injury rehabilitation. Interventions Not applicable. Main Outcome Measures FIM instrument, Disability Rating Scale, Supervision Rating Scale, Satisfaction With Life Scale (SWLS), and Glasgow Outcome Scale−Extended. Results Multiple regression analyses revealed that performance on the neuropsychologic test battery was predictive of outcome at 1 year postinjury for all outcome measures, except FIM motor scores and the SWLS. Cognitive performance using this battery was found to predict 1-year outcomes above and beyond functional variables and injury severity variables collected during inpatient rehabilitation, thereby indicating incremental validity for this test battery. Individual tests that were found to be significant predictors of 1-year outcomes included the WTAR and TMT part B. Conclusions These findings support the clinical utility and ecological validity of this battery with respect to level of disability, functional independence, and supervision required.