The effects of combat-related mild traumatic brain injury (mTBI): Does blast mTBI history matter?

PubMed

Kontos, Anthony P; Elbin, R J; Kotwal, Russ S; Lutz, Robert H; Kane, Shawn; Benson, Peter J; Forsten, Robert D; Collins, Michael W

2015-10-01

The effects of mild traumatic brain injury (mTBI) have received significant attention since the beginning of the conflicts in Afghanistan and Iraq. Surprisingly, little is known about the temporal nature of neurocognitive impairment, mTBI, and posttraumatic stress (PTS) symptoms following combat-related mTBI. It is also unclear as to the role that blast exposure history has on mTBI and PTS impairments and symptoms. The purposes of this study were to examine prospectively the effects of mTBI on neurocognitive performance as well as mTBI and PTS symptoms among US Army Special Operations Command personnel and to study the influence of history of blast mTBI on these effects. Eighty US Army Special Operations Command personnel with (n = 19) and without (n = 61) a history of blast-related mTBI completed the military version of the Immediate Post-concussion Assessment Cognitive Test (ImPACT), Post Concussion Symptom Scale (PCSS), and the PTSD Checklist (PCL) at baseline as well as 1 day to 7 days and 8 days to 20 days following a combat-related mTBI. Results indicated that verbal memory (p = 0.002) and processing speed (p = 0.003) scores were significantly lower and mTBI symptoms (p = 0.001) were significantly higher at 1 day to 7 days after injury compared with both baseline and 8 days to 20 days after injury. PTS remained stable across the three periods. Participants with a history of blast mTBI demonstrated lower verbal memory at 1 day to 7 days after mTBI compared with participants without a history of blast mTBI (p = 0.02). Decreases in neurocognitive performance and increased mTBI symptoms are evident in the first 1 day to 7 days following combat-related mTBI, and a history of blast-related mTBI may influence these effects. Epidemiologic/prognostic study, level II.

The Effects of Lactobacillus acidophilus on the Intestinal Smooth Muscle Contraction through PKC/MLCK/MLC Signaling Pathway in TBI Mouse Model

PubMed Central

Fang, Huan; Zhu, Lina; Gao, Ning; Zhu, Jingci

2015-01-01

Clinical studies have shown that probiotics influence gastrointestinal motility. However, the molecular mechanisms by which probiotic Lactobacillus modulates intestinal motility in traumatic brain injury (TBI) mouse model have not been explored. In the present study, we provided evidence showing that treatment of TBI mice with Lactobacillus acidophilus significantly improved the terminal ileum villus morphology, restored the impaired interstitial cells of Cajal (ICC) and the disrupted ICC networks after TBI, and prevented TBI-mediated inhibition of contractile activity in intestinal smooth muscle. Mechanistically, the decreased concentration of MLCK, phospho-MLC20 and phospho-MYPT1 and increased concentration of MLCP and PKC were observed after TBI, and these events mediated by TBI were efficiently prevented by Lactobacillus acidophilus application. These findings may provide a novel mechanistic basis for the application of Lactobacillus acidophilus in the treatment of TBI. PMID:26030918

The Effects of Lactobacillus acidophilus on the Intestinal Smooth Muscle Contraction through PKC/MLCK/MLC Signaling Pathway in TBI Mouse Model.

PubMed

Sun, Bo; Hu, Chen; Fang, Huan; Zhu, Lina; Gao, Ning; Zhu, Jingci

2015-01-01

Clinical studies have shown that probiotics influence gastrointestinal motility. However, the molecular mechanisms by which probiotic Lactobacillus modulates intestinal motility in traumatic brain injury (TBI) mouse model have not been explored. In the present study, we provided evidence showing that treatment of TBI mice with Lactobacillus acidophilus significantly improved the terminal ileum villus morphology, restored the impaired interstitial cells of Cajal (ICC) and the disrupted ICC networks after TBI, and prevented TBI-mediated inhibition of contractile activity in intestinal smooth muscle. Mechanistically, the decreased concentration of MLCK, phospho-MLC20 and phospho-MYPT1 and increased concentration of MLCP and PKC were observed after TBI, and these events mediated by TBI were efficiently prevented by Lactobacillus acidophilus application. These findings may provide a novel mechanistic basis for the application of Lactobacillus acidophilus in the treatment of TBI.

A randomised control trial of walking to ameliorate brain injury fatigue: a NIDRR TBI model system centre-based study.

PubMed

Kolakowsky-Hayner, Stephanie A; Bellon, Kimberly; Toda, Ketra; Bushnik, Tamara; Wright, Jerry; Isaac, Linda; Englander, Jeffrey

2017-10-01

Fatigue is one of the most commonly reported sequelae after traumatic brain injury (TBI). This study evaluated the impact of a graduated physical activity programme on fatigue after TBI. Using a prospective randomised single-blind crossover design, 123 individuals with TBI, over the age of 18, were enrolled. Interventions included a home-based walking programme utilising a pedometer to track daily number of steps at increasing increments accompanied by tapered coaching calls over a 12-week period. Nutritional counselling with the same schedule of coaching calls served as the control condition. Main outcome measures included: the Global Fatigue Index (GFI), the Barrow Neurological Institute (BNI) Fatigue Scale Overall Severity Index Score, and the Multidimensional Fatigue Inventory (MFI). Step counts improved over time regardless of group assignment. The walking intervention led to a decrease in GFI, BNI Total, and MFI General scores. Participants reported less fatigue at the end of the active part of the intervention (24 weeks) and after a wash out period (36 weeks) as measured by the BNI Overall. The study suggests that walking can be used as an efficient and cost-effective tool to improve fatigue in persons who have sustained a TBI.

Traumatic Brain Injury (TBI) in Kids

MedlinePlus

... Information Share Facebook Twitter Pinterest Email Print Traumatic Brain Injury (TBI): Condition Information What is TBI? TBI ... external force that affects the functioning of the brain. It can be caused by a bump or ...

Towards Development of a Field-Deployable Imaging Device for TBI

DTIC Science & Technology

2012-03-01

accompany TBI, and that ultrasound-based ‘sonoelastic’ imaging modalities responsive to some measure of stiffness might offer a useful means for imaging the...changes to brain due to TBI. Use of such systems in and near the field should improve clinical outcome for patients suffering from TBI. Our long...sonoelastic’ imaging modalities responsive to some measure of stiffness might offer a useful means for imaging the gross and subtle changes to brain

Trajectories of life satisfaction after TBI: Influence of life roles, age, cognitive disability, and depressive symptoms

PubMed Central

Juengst, Shannon B.; Adams, Leah M.; Bogner, Jennifer A.; Arenth, Patricia M.; O’Neil-Pirozzi, Therese M.; Dreer, Laura E.; Hart, Tessa; Bergquist, Thomas F.; Bombardier, Charles H.; Dijkers, Marcel P.; Wagner, Amy K.

2015-01-01

Objectives 1) Identify life satisfaction trajectories after moderate to severe traumatic brain injury (TBI), 2) establish a predictive model for these trajectories across the first 5 years post-injury, and 3) describe differences in these life satisfaction trajectory groups, focusing on age, depressive symptoms, disability, and participation in specific life roles,. Research Method Analysis of the longitudinal TBI Model Systems National Database was performed on data collected prospectively at 1, 2, and 5 years post-TBI. Participants (n=3,012) had a moderate to severe TBI and were 16 years old and older. Results Four life satisfaction trajectories were identified across the first 5 years post-injury, including: Stable Satisfaction, Initial Satisfaction Declining, Initial Dissatisfaction Improving, and Stable Dissatisfaction. Age, depressive symptoms, cognitive disability, and life role participation as a worker, leisure participant, and/ or religious participant at one year post-injury significantly predicted trajectory group membership. Life role participation and depressive symptoms were strong predictors of life satisfaction trajectories across the first 5 years post TBI. Conclusions The previously documented loss of life roles and prevalence of depression after a moderate to severe TBI make this a vulnerable population for whom low or declining life satisfaction is a particularly high risk. Examining individual life role participation may help to identify relevant foci for community-based rehabilitation interventions or supports. PMID:26618215

Legacy Clinical Data from the Epo TBI Trial

DTIC Science & Technology

2015-10-01

Anemia in Traumatic Brain Injury (TBI)” which we will share with other investigators through the Federal Interagency Traumatic Brain Injury (FITBIR... Informatics System. This trial was funded by National Institute of Neurological Disorders and Stroke (NINDS) grant #P01-NS38660. The study began...Data Elements (CDEs) for TBI, and therefore requires work to convert the data to the format required by FITBIR. 2. KEYWORDS: Traumatic brain

Similar Survival for Patients Undergoing Reduced-Intensity Total Body Irradiation (TBI) Versus Myeloablative TBI as Conditioning for Allogeneic Transplant in Acute Leukemia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mikell, John L., E-mail: jmikell@emory.edu; Waller, Edmund K.; Switchenko, Jeffrey M.

Purpose: Hematopoietic stem cell transplantation (HSCT) is the mainstay of treatment for adults with acute leukemia. Total body irradiation (TBI) remains an important part of the conditioning regimen for HCST. For those patients unable to tolerate myeloablative TBI (mTBI), reduced intensity TBI (riTBI) is commonly used. In this study we compared outcomes of patients undergoing mTBI with those of patients undergoing riTBI in our institution. Methods and Materials: We performed a retrospective review of all patients with acute leukemia who underwent TBI-based conditioning, using a prospectively acquired database of HSCT patients treated at our institution. Patient data including details ofmore » the transplantation procedure, disease status, Karnofsky performance status (KPS), response rates, toxicity, survival time, and time to progression were extracted. Patient outcomes for various radiation therapy regimens were examined. Descriptive statistical analysis was performed. Results: Between June 1985 and July 2012, 226 patients with acute leukemia underwent TBI as conditioning for HSCT. Of those patients, 180 had full radiation therapy data available; 83 had acute lymphoblastic leukemia and 94 had acute myelogenous leukemia; 45 patients received riTBI, and 135 received mTBI. Median overall survival (OS) was 13.7 months. Median relapse-free survival (RFS) for all patients was 10.2 months. Controlling for age, sex, KPS, disease status, and diagnosis, there were no significant differences in OS or RFS between patients who underwent riTBI and those who underwent mTBI (P=.402, P=.499, respectively). Median length of hospital stay was shorter for patients who received riTBI than for those who received mTBI (16 days vs 23 days, respectively; P<.001), and intensive care unit admissions were less frequent following riTBI than mTBI (2.22% vs 12.69%, respectively, P=.043). Nonrelapse survival rates were also similar (P=.186). Conclusions: No differences in OS or RFS were seen

Leveraging Game Consoles for the Delivery of TBI Rehabilitation

NASA Technical Reports Server (NTRS)

Super, Taryn; Mastaglio, Thomas; Shen, Yuzhong; Walker, Robert

2011-01-01

Military personnel are at a greater risk for traumatic brain injury (TBI) than the civilian population. In addition, the increase in exposure to explosives, i.e. , improvised explosive devices, in the Afghanistan and Iraq wars, along with more effective body armor, has resulted in far more surviving casualties suffering from TBI than in previous wars. This effort presents the results of a feasibility study and early prototype of a brain injury rehabilitation delivery system (BIRDS). BIRDS is designed to provide medical personnel treating TBI with a capability to prescribe game activities for patients to execute using a commercially available game console, either in a clinical setting or in their homes. These therapeutic activities will contribute to recovery or remediation of the patients' cognitive dysfunctions. Solutions such as this that provide new applications for existing platforms have significant potential to address the growing incidence of TBI today.

TBI Assessment of Readiness Using a Gait Evaluation Test (TARGET): Development of a Portable mTBI Screening Device

DTIC Science & Technology

2017-05-01

AWARD NUMBER: W81XWH-15-1-0094 TITLE: TBI Assessment of Readiness Using a Gait Evaluation Test (TARGET): Development of a Portable mTBI Screening...Annual 3. DATES COVERED 1 May 2016 - 30 Apr 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER “TBI Assessment of Readiness Using a Gait Evaluation ...service members sustaining some form of traumatic brain injury (TBI) over the past 14 years, the lack of an objective measurement tool for evaluation

Defining the Pathophysiological Role of Tau in Experimental TBI

DTIC Science & Technology

2016-10-01

in AD. This pathway is a major source for excitatory innervation of hippocampus , a structure vital for memory formation. Damage to the EC or...hippocampal input pathway that is both preferentially vulnerable in early-stage AD and critically important for long-term memory . The model confines...structure and function of the hippocampus after single or repetitive mild TBI, and whether mild TBI exacerbates ongoing tauopathy to promote a chronic

Pre-injury psychosocial and demographic predictors of long-term functional outcomes post-TBI.

PubMed

Seagly, Katharine S; O'Neil, Rochelle L; Hanks, Robin A

2018-01-01

To determine whether pre-injury psychosocial and demographic factors differentially influence long-term functional outcomes post-TBI. Urban rehabilitation hospital. 149 individuals, ages 16-75, who sustained a mild complicated, moderate or severe TBI, were enrolled in a TBI Model System (TBIMS), and had functional outcome data five-15 years post-injury. Archival data were analysed with SPSS-18 using multiple regression to determine amount of variance accounted for in five functional domains. Predictors included age at injury, pre-injury education, Glasgow Coma Scale (GCS), pre-injury incarceration and psychiatric history. Craig Handicap Assessment and Reporting Technique (CHART), including Cognitive Independence, Physical Independence, Mobility, Occupation and Social Integration domains. Models were significant for Cognitive and Physical Independence, Mobility, and Occupation. Incarceration and psychiatric history accounted for the most variance in Cognitive and Physical Independence, over and above GCS and age at injury. Psychiatric history was also the strongest predictor of Occupation. Mobility was the only domain in which GCS accounted for the most variance. Pre-injury psychosocial and demographic factors may be more important than injury severity for predicting some long-term functional outcomes post-TBI. It would likely be beneficial to assess these factors in the inpatient setting, with input from a multidisciplinary team, as an early understanding of prognostic indicators can help guide treatment for optimal functional outcomes.

Using the public health model to address unintentional injuries and TBI: A perspective from the Centers for Disease Control and Prevention (CDC).

PubMed

Baldwin, Grant; Breiding, Matt; Sleet, David

2016-06-30

Traumatic brain injury (TBI) can have long term effects on mental and physical health, and can disrupt vocational, educational, and social functioning. TBIs can range from mild to severe and their effects can last many years after the initial injury. CDC seeks to reduce the burden of TBI from unintentional injuries through a focus on primary prevention, improved recognition and management, and intervening to improve health outcomes after TBI. CDC uses a 4-stage public health model to guide TBI prevention, moving from 1) surveillance of TBI, 2) identification of risk and protective factors for TBI, 3) development and testing of evidence-based interventions, to 4) bringing effective intervention to scale through widespread adoption. CDC's unintentional injury prevention activities focus on the prevention of sports-related concussions, motor vehicle crashes, and older adult falls. For concussion prevention, CDC developed Heads Up - an awareness initiative focusing on ways to prevent a concussion in sports, and identifying how to recognize and manage potential concussions. In motor vehicle injury prevention, CDC has developed a tool (MV PICCS) to calculate the expected number of injuries prevented and lives saved using various evidence-based motor vehicle crash prevention strategies. To help prevent TBI related to older adult falls, CDC has developed STEADI, an initiative to help primary care providers identify their patients' falls risk and provide effective interventions. In the future, CDC is focused on advancing our understanding of the public health burden of TBI through improved surveillance in order to produce more comprehensive estimates of the public health burden of TBI.

Validating Multidimensional Outcome Assessment Using the TBI Common Data Elements: An Analysis of the TRACK-TBI Pilot Sample.

PubMed

Nelson, Lindsay D; Ranson, Jana; Ferguson, Adam R; Giacino, Joseph; Okonkwo, David O; Valadka, Alex; Manley, Geoffrey; McCrea, Michael

2017-06-08

The Glasgow Outcome Scale-Extended (GOSE) is often the primary outcome measure in clinical trials for traumatic brain injury (TBI). Although the GOSE's capture of global function outcome has several strengths, concerns have been raised about its limited ability to identify mild disability and failure to capture the full scope of problems patients exhibit after TBI. This analysis examined the convergence of disability ratings across a multidimensional set of outcome domains in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Pilot study. The study collected measures recommended by the TBI Common Data Elements (CDE) Workgroup. Patients presenting to 3 emergency departments with a TBI of any severity enrolled in TRACK-TBI prospectively after injury; outcome measures were collected at 3 and six months postinjury. Analyses examined frequency of impairment and overlap between impairment status across the CDE outcome domains of Global Level of Functioning (GOSE), Neuropsychological (cognitive) Impairment, Psychological Status, TBI Symptoms, and Quality of Life. GOSE score correlated in the expected direction with other outcomes (M Spearman's rho = .21 and .49 with neurocognitive and self-report outcomes, respectively). The subsample in the Upper Good Recovery (GOSE 8) category appeared quite healthy across most other outcomes, although 19.0% had impaired executive functioning (Trail Making Test Part B). A significant minority of participants in the Lower Good Recovery subgroup (GOSE 7) met criteria for impairment across numerous other outcome measures. The findings highlight the multidimensional nature of TBI recovery and the limitations of applying only a single outcome measure.

Verification of an on line in vivo semiconductor dosimetry system for TBI with two TLD procedures.

PubMed

Sánchez-Doblado, F; Terrón, J A; Sánchez-Nieto, B; Arráns, R; Errazquin, L; Biggs, D; Lee, C; Núñez, L; Delgado, A; Muñiz, J L

1995-01-01

This work presents the verification of an on line in vivo dosimetry system based on semiconductors. Software and hardware has been designed to convert the diode signal into absorbed dose. Final verification was made in the form of an intercomparison with two independent thermoluminiscent (TLD) dosimetry systems, under TBI conditions.

Blast TBI Models, Neuropathology, and Implications for Seizure Risk

PubMed Central

Kovacs, S. Krisztian; Leonessa, Fabio; Ling, Geoffrey S. F.

2014-01-01

Traumatic brain injury (TBI) due to explosive blast exposure is a leading combat casualty. It is also implicated as a key contributor to war related mental health diseases. A clinically important consequence of all types of TBI is a high risk for development of seizures and epilepsy. Seizures have been reported in patients who have suffered blast injuries in the Global War on Terror but the exact prevalence is unknown. The occurrence of seizures supports the contention that explosive blast leads to both cellular and structural brain pathology. Unfortunately, the exact mechanism by which explosions cause brain injury is unclear, which complicates development of meaningful therapies and mitigation strategies. To help improve understanding, detailed neuropathological analysis is needed. For this, histopathological techniques are extremely valuable and indispensable. In the following we will review the pathological results, including those from immunohistochemical and special staining approaches, from recent preclinical explosive blast studies. PMID:24782820

Advanced MRI in Blast-related TBI

DTIC Science & Technology

2012-07-01

test two advanced MRI methods, DTI and resting-state fMRI, in active-duty military blast-related TBI patients acutely after injury and correlate...Introduction: The purpose of the research effort was to test two advanced MRI methods, DTI and resting-state fMRI, in active-duty military blast-related TBI...clinical follow-up assessments and repeat scans on 78 subjects with TBI and 18 controls. 9) We extensively analyzed DTI , resting-state fMRI, and

Advanced Sensors for TBI

DTIC Science & Technology

2015-07-01

CMOS clean • Commercialization of the sensor is aided by this process as use of CMOS -clean commercial foundries will not be restricted Bench...AD_________________ Award Number: W81XWH-10-2-0040 TITLE: Advanced Sensors for TBI PRINCIPAL INVESTIGATOR: Bruce Lyeth, Ph.D. CONTRACTING...ABOVE ADDRESS. 1. REPORT DATE July 2015 2. REPORT TYPE Annual 3. DATES COVERED 1Jul2014 - 30Jun2015 4. TITLE AND SUBTITLE Advanced Sensors for TBI 5a

Targeting Epigenetic Mechanisms in Pain Due to Trauma and Traumatic Brain Injury (TBI)

DTIC Science & Technology

2015-10-01

particularly likely to involve TBI, peripheral trauma or both. Disability due to pain and other causes is very high amongst such patients. We have no...effective approaches to reducing the likelihood of developing chronic pain after TBI or peripheral injuries, and the mechanisms supporting such pain...brain or peripheral trauma may support chronic pain. Our work to-date has established a rodent model of TBI in combination with injury to a limb as a

Mechanistic Links Between PARP, NAD, and Brain Inflammation After TBI

DTIC Science & Technology

2015-10-01

1 AWARD NUMBER: W81XWH-13-2-0091 TITLE: Mechanistic Links Between PARP, NAD , and Brain Inflammation After TBI PRINCIPAL INVESTIGATOR...COVERED 25 Sep 2014 - 24 Sep 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Mechanistic Links Between PARP, NAD , and Brain Inflammation After TBI 5b. GRANT...efficacy of veliparib and NAD as agents for suppressing inflammation and improving outcomes after traumatic brain injury. The animal models include

Targeting Epigenetic Mechanisms in Pain due to Trauma and TBI

DTIC Science & Technology

2017-10-01

pain by Anacardic acid. Karen Amanda Irvine, Peyman Sahbaie, De-Yong Liang, J. David Clark. Journal of Neurotrauma (Submitted). 4. Sex differences in...CA on Nov. 15, 2016. 17  2. Sex differences in nociceptive alterations and cognitive impairments in a preclinical model of polytrauma. Presented at...TBI Research Forum annual meeting at VA Palo Alto Health Care System, CA on March 31, 2017. 3. Sex differences in nociceptive alterations and

Formononetin protects TBI rats against neurological lesions and the underlying mechanism.

PubMed

Li, Zhengzhao; Dong, Xianhong; Zhang, Jianfeng; Zeng, Guang; Zhao, Huimin; Liu, Yun; Qiu, Rubiao; Mo, Linjian; Ye, Yu

2014-03-15

Traumatic brain injury (TBI) is a major cause of disability or death worldwide, especially in the young. Thus, effective medication with few side effects needs to be developed. This work aimed to explore the potential benefits of formononetin (FN) on TBI rodent model and to discuss the regarding mechanism. These findings showed that FN effectively increased the activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in brain tissue of TBI rats (P<0.01), while it reduced intracephalic malonaldehyde (MDA), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) concentrations (P<0.01). Meanwhile, the hydrocephalus in the TBI rat was alleviated, and the injured nerve cell of the lesioned brain was reduced as showed in hematoxylin-eosin (HE) staining assay. In addition, the endogenous mRNA level of cyclooxygenase-2 (COX-2) in the brain of the TBI rat was significantly down-regulated (P<0.01). Furthermore, the protein expression of nuclear factor E2-related factor 2 (Nrf2) was effectively up-regulated (P<0.01). Taken together, we conclude that formononetin mediates the promising anti-TBI effects against neurocyte damage, which the underlying mechanisms are associated with inhibiting intracephalic inflammatory response and oxidative stress for neuroprotection. Copyright © 2013 Elsevier B.V. All rights reserved.

The consequence of spatial visual processing dysfunction caused by traumatic brain injury (TBI).

PubMed

Padula, William V; Capo-Aponte, Jose E; Padula, William V; Singman, Eric L; Jenness, Jonathan

2017-01-01

A bi-modal visual processing model is supported by research to affect dysfunction following a traumatic brain injury (TBI). TBI causes dysfunction of visual processing affecting binocularity, spatial orientation, posture and balance. Research demonstrates that prescription of prisms influence the plasticity between spatial visual processing and motor-sensory systems improving visual processing and reducing symptoms following a TBI. The rationale demonstrates that visual processing underlies the functional aspects of binocularity, balance and posture. The bi-modal visual process maintains plasticity for efficiency. Compromise causes Post Trauma Vision Syndrome (PTVS) and Visual Midline Shift Syndrome (VMSS). Rehabilitation through use of lenses, prisms and sectoral occlusion has inter-professional implications in rehabilitation affecting the plasticity of the bi-modal visual process, thereby improving binocularity, spatial orientation, posture and balance Main outcomes: This review provides an opportunity to create a new perspective of the consequences of TBI on visual processing and the symptoms that are often caused by trauma. It also serves to provide a perspective of visual processing dysfunction that has potential for developing new approaches of rehabilitation. Understanding vision as a bi-modal process facilitates a new perspective of visual processing and the potentials for rehabilitation following a concussion, brain injury or other neurological events.

The protective effect of hydrogen sulfide (H2S) on traumatic brain injury (TBI) induced memory deficits in rats.

PubMed

Karimi, Seyed Asaad; Hosseinmardi, Narges; Janahmadi, Mahyar; Sayyah, Mohammad; Hajisoltani, Razieh

2017-09-01

Traumatic brain injury (TBI), as an expanding public health epidemic, is a common cause of death among youth. TBI is associated with cognitive deficits and memory impairment. Hydrogen sulfide (H 2 S), a novel gaseous mediator, has been recognized as an important neuromodulator and neuroprotective agent in the central nervous system. In the present study the potential neuroprotective role of sodium hydrosulfide (NaHS), an H 2 S donor on TBI induced memory deficit in a rat model of controlled cortical impact (CCI) injury was investigated. CCI model was used to induce TBI. Male rats were randomly assigned into the following groups: control, sham, sham treated with NaHS, TBI, and TBI treated with NaHS (3 and 5mg/kg). NaHS was injected intraperitoneally 5min before TBI induction. Learning and memory were assessed using Morris water maze (MWM) on days 8-12 following injury. CCI resulted in MWM deficits. Injured animals showed a slower rate of acquisition with respect to the sham-operated animals [F (1, 24)=13.97, P<0.01, two-way ANOVA]. NaHS improved spatial memory impairment of injured rats. Treatment with NaHS (5 mg/kg) decreased the escape latency [F (1, 24)=7.559, P<0.05, two-way ANOVA] and traveled distance [F (1, 12)=6.398, P<0.05, Two way ANOVA)]. In probe test, injured animals spent less time in target zone (P<0.05, unpaired t-test) and NaHS did not have any effect on this parameter (p>0.05, one way ANOVA). These findings suggest that NaHS has a neuroprotective effect on TBI-induced memory impairment in rats. Copyright © 2017 Elsevier Inc. All rights reserved.

Development and Initial Validation of Military Deployment-Related TBI Quality-of-Life Item Banks.

PubMed

Toyinbo, Peter A; Vanderploeg, Rodney D; Donnell, Alison J; Mutolo, Sandra A; Cook, Karon F; Kisala, Pamela A; Tulsky, David S

2016-01-01

To investigate unique factors that affect health-related quality of life (QOL) in individuals with military deployment-related traumatic brain injury (MDR-TBI) and to develop appropriate assessment tools, consistent with the TBI-QOL/PROMIS/Neuro-QOL systems. Three focus groups from each of the 4 Veterans Administration (VA) Polytrauma Rehabilitation Centers, consisting of 20 veterans with mild to severe MDR-TBI, and 36 VA providers were involved in early stage of new item banks development. The item banks were field tested in a sample (N = 485) of veterans enrolled in VA and diagnosed with an MDR-TBI. Focus groups and survey. Developed item banks and short forms for Guilt, Posttraumatic Stress Disorder/Trauma, and Military-Related Loss. Three new item banks representing unique domains of MDR-TBI health outcomes were created: 15 new Posttraumatic Stress Disorder items plus 16 SCI-QOL legacy Trauma items, 37 new Military-Related Loss items plus 18 TBI-QOL legacy Grief/Loss items, and 33 new Guilt items. Exploratory and confirmatory factor analyses plus bifactor analysis of the items supported sufficient unidimensionality of the new item pools. Convergent and discriminant analyses results, as well as known group comparisons, provided initial support for the validity and clinical utility of the new item response theory-calibrated item banks and their short forms. This work provides a unique opportunity to identify issues specific to individuals with MDR-TBI and ensure that they are captured in QOL assessment, thus extending the existing TBI-QOL measurement system.

Internet and Social Media Use After Traumatic Brain Injury: A Traumatic Brain Injury Model Systems Study.

PubMed

Baker-Sparr, Christina; Hart, Tessa; Bergquist, Thomas; Bogner, Jennifer; Dreer, Laura; Juengst, Shannon; Mellick, David; OʼNeil-Pirozzi, Therese M; Sander, Angelle M; Whiteneck, Gale G

To characterize Internet and social media use among adults with moderate to severe traumatic brain injury (TBI) and to compare demographic and socioeconomic factors associated with Internet use between those with and without TBI. Ten Traumatic Brain Injury Model Systems centers. Persons with moderate to severe TBI (N = 337) enrolled in the TBI Model Systems National Database and eligible for follow-up from April 1, 2014, to March 31, 2015. Prospective cross-sectional observational cohort study. Internet usage survey. The proportion of Internet users with TBI was high (74%) but significantly lower than those in the general population (84%). Smartphones were the most prevalent means of Internet access for persons with TBI. The majority of Internet users with TBI had a profile account on a social networking site (79%), with more than half of the sample reporting multiplatform use of 2 or more social networking sites. Despite the prevalence of Internet use among persons with TBI, technological disparities remain in comparison with the general population. The extent of social media use among persons with TBI demonstrates the potential of these platforms for social engagement and other purposes. However, further research examining the quality of online activities and identifying potential risk factors of problematic use is recommended.

Mathematical outcomes and working memory in children with TBI and orthopedic injury.

PubMed

Raghubar, Kimberly P; Barnes, Marcia A; Prasad, Mary; Johnson, Chad P; Ewing-Cobbs, Linda

2013-03-01

This study compared mathematical outcomes in children with predominantly moderate to severe traumatic brain injury (TBI; n550) or orthopedic injury (OI; n547) at 2 and 24 months post-injury. Working memory and its contribution to math outcomes at 24 months post-injury was also examined. Participants were administered an experimental cognitive addition task and standardized measures of calculation, math fluency, and applied problems; as well as experimental measures of verbal and visual-spatial working memory. Although children with TBI did not have deficits in foundational math fact retrieval, they performed more poorly than OIs on standardized measures of math. In the TBI group, performance on standardized measures was predicted by age at injury, socioeconomic status, and the duration of impaired consciousness. Children with TBI showed impairments on verbal, but not visual working memory relative to children with OI. Verbal working memory mediated group differences on math calculations and applied problems at 24 months post-injury. Children with TBI have difficulties in mathematics, but do not have deficits in math fact retrieval, a signature deficit of math disabilities. Results are discussed with reference to models of mathematical cognition and disability and the role of working memory in math learning and performance for children with TBI.

Mathematical Outcomes and Working Memory in Children With TBI and Orthopedic Injury

PubMed Central

Raghubar, Kimberly P.; Barnes, Marcia A.; Prasad, Mary; Johnson, Chad P.; Ewing-Cobbs, Linda

2013-01-01

This study compared mathematical outcomes in children with predominantly moderate to severe traumatic brain injury (TBI; n =50) or orthopedic injury (OI; n=47) at 2 and 24 months post-injury. Working memory and its contribution to math outcomes at 24 months post-injury was also examined. Participants were administered an experimental cognitive addition task and standardized measures of calculation, math fluency, and applied problems; as well as experimental measures of verbal and visual-spatial working memory. Although children with TBI did not have deficits in foundational math fact retrieval, they performed more poorly than OIs on standardized measures of math. In the TBI group, performance on standardized measures was predicted by age at injury, socioeconomic status, and the duration of impaired consciousness. Children with TBI showed impairments on verbal, but not visual working memory relative to children with OI. Verbal working memory mediated group differences on math calculations and applied problems at 24 months post-injury. Children with TBI have difficulties in mathematics, but do not have deficits in math fact retrieval, a signature deficit of math disabilities. Results are discussed with reference to models of mathematical cognition and disability and the role of working memory in math learning and performance for children with TBI. PMID:23164058

Neutrophils in traumatic brain injury (TBI): friend or foe?

PubMed

Liu, Yang-Wuyue; Li, Song; Dai, Shuang-Shuang

2018-05-17

Our knowledge of the pathophysiology about traumatic brain injury (TBI) is still limited. Neutrophils, as the most abundant leukocytes in circulation and the first-line transmigrated immune cells at the sites of injury, are highly involved in the initiation, development, and recovery of TBI. Nonetheless, our understanding about neutrophils in TBI is obsolete, and mounting evidences from recent studies have challenged the conventional views. This review summarizes what is known about the relationships between neutrophils and pathophysiology of TBI. In addition, discussions are made on the complex roles as well as the controversial views of neutrophils in TBI.

Traumatic Brain Injury (TBI) Data and Statistics

MedlinePlus

... data.cdc.gov . Emergency Department Visits, Hospitalizations, and Deaths Rates of TBI-related Emergency Department Visits, Hospitalizations, ... related Hospitalizations by Age Group and Injury Mechanism Deaths Rates of TBI-related Deaths by Sex Rates ...

Frontoparietal Priority Maps as Biomarkers for mTBI

DTIC Science & Technology

2015-10-01

preliminary data analysis is underway. 15. SUBJECT TERMS mTBI, fMRI , DTI, psychophysics, vision, convergence insufficiency 16. SECURITY CLASSIFICATION OF...biomarkers and behavioral measures of visual performance in veterans who have and have not experienced mTBI. KEYWORDS mTBI fMRI DTI psychophysics...MRI protocol prepared 8 Delayed to month 15 due to recruitment delays. Major Task 5: acquire MRI measures, which include DTI and fMRI Complete

Pupillometry and Saccades as Objective mTBI Biomarker

DTIC Science & Technology

2016-10-01

INTRODUCTION: The DOD reported that 333,169 cases of traumatic brain injury (TBI) were confirmed since 2000, with mild TBI (mTBI) accounting for 82.4...Complete final report: NO INITIATED (A 6-month No Cost Extension was approved to complete data analysis and manuscript writing.) KEY RESEARCH...Staff hiring issues delayed study completion; however a 6-month No Cost extension was approved Budget Expenditure to Date Projected Expenditure

EEG Monitoring and Antiepileptic Drugs in Children with Severe TBI.

PubMed

Ruzas, Christopher M; DeWitt, Peter E; Bennett, Kimberly S; Chapman, Kevin E; Harlaar, Nicole; Bennett, Tellen D

2017-04-01

Traumatic brain injury (TBI) causes substantial morbidity and mortality in US children. Post-traumatic seizures (PTS) occur in 11-42% of children with severe TBI and are associated with unfavorable outcome. Electroencephalographic (EEG) monitoring may be used to detect PTS and antiepileptic drugs (AEDs) may be used to treat PTS, but national rates of EEG and AED use are not known. The purpose of this study was to describe the frequency and timing of EEG and AED use in children hospitalized after severe TBI. Retrospective cohort study of 2165 children at 30 hospitals in a probabilistically linked dataset from the National Trauma Data Bank (NTDB) and the Pediatric Health Information Systems (PHIS) database, 2007-2010. We included children (age <18 years old at admission) with linked NTDB and PHIS records, severe (Emergency Department [ED] Glasgow Coma Scale [GCS] <8) TBI, hospital length of stay >24 h, and non-missing disposition. The primary outcomes were EEG and AED use. Overall, 31.8% of the cohort had EEG monitoring. Of those, 21.8% were monitored on the first hospital day. The median duration of EEG monitoring was 2.0 (IQR 1.0, 4.0) days. AEDs were prescribed to 52.0% of the cohort, of whom 61.8% received an AED on the first hospital day. The median duration of AED use was 8.0 (IQR 4.0, 17.0) days. EEG monitoring and AED use were more frequent in children with known risk factors for PTS. EEG monitoring and AED use were not related to hospital TBI volume. EEG use is relatively uncommon in children with severe TBI, but AEDs are frequently prescribed. EEG monitoring and AED use are more common in children with known risk factors for PTS.

Greater neurobehavioral deficits occur in adult mice after repeated, as compared to single, mild traumatic brain injury (mTBI).

PubMed

Nichols, Jessica N; Deshane, Alok S; Niedzielko, Tracy L; Smith, Cory D; Floyd, Candace L

2016-02-01

Mild traumatic brain injury (mTBI) accounts for the majority of all brain injuries and affected individuals typically experience some extent of cognitive and/or neuropsychiatric deficits. Given that repeated mTBIs often result in worsened prognosis, the cumulative effect of repeated mTBIs is an area of clinical concern and on-going pre-clinical research. Animal models are critical in elucidating the underlying mechanisms of single and repeated mTBI-associated deficits, but the neurobehavioral sequelae produced by these models have not been well characterized. Thus, we sought to evaluate the behavioral changes incurred after single and repeated mTBIs in mice utilizing a modified impact-acceleration model. Mice in the mTBI group received 1 impact while the repeated mTBI group received 3 impacts with an inter-injury interval of 24h. Classic behavior evaluations included the Morris water maze (MWM) to assess learning and memory, elevated plus maze (EPM) for anxiety, and forced swim test (FST) for depression/helplessness. Additionally, species-typical behaviors were evaluated with the marble-burying and nestlet shredding tests to determine motivation and apathy. Non-invasive vibration platforms were used to examine sleep patterns post-mTBI. We found that the repeated mTBI mice demonstrated deficits in MWM testing and poorer performance on species-typical behaviors. While neither single nor repeated mTBI affected behavior in the EPM or FST, sleep disturbances were observed after both single and repeated mTBI. Here, we conclude that behavioral alterations shown after repeated mTBI resemble several of the deficits or disturbances reported by patients, thus demonstrating the relevance of this murine model to study repeated mTBIs. Copyright © 2015 Elsevier B.V. All rights reserved.

Cerebrospinal Fluid Cortisol Mediates Brain-Derived Neurotrophic Factor Relationships to Mortality after Severe TBI: A Prospective Cohort Study

PubMed Central

Munoz, Miranda J.; Kumar, Raj G.; Oh, Byung-Mo; Conley, Yvette P.; Wang, Zhensheng; Failla, Michelle D.; Wagner, Amy K.

2017-01-01

Distinct regulatory signaling mechanisms exist between cortisol and brain derived neurotrophic factor (BDNF) that may influence secondary injury cascades associated with traumatic brain injury (TBI) and predict outcome. We investigated concurrent CSF BDNF and cortisol relationships in 117 patients sampled days 0–6 after severe TBI while accounting for BDNF genetics and age. We also determined associations between CSF BDNF and cortisol with 6-month mortality. BDNF variants, rs6265 and rs7124442, were used to create a gene risk score (GRS) in reference to previously published hypothesized risk for mortality in “younger patients” (<48 years) and hypothesized BDNF production/secretion capacity with these variants. Group based trajectory analysis (TRAJ) was used to create two cortisol groups (high and low trajectories). A Bayesian estimation approach informed the mediation models. Results show CSF BDNF predicted patient cortisol TRAJ group (P = 0.001). Also, GRS moderated BDNF associations with cortisol TRAJ group. Additionally, cortisol TRAJ predicted 6-month mortality (P = 0.001). In a mediation analysis, BDNF predicted mortality, with cortisol acting as the mediator (P = 0.011), yielding a mediation percentage of 29.92%. Mediation effects increased to 45.45% among younger patients. A BDNF*GRS interaction predicted mortality in younger patients (P = 0.004). Thus, we conclude 6-month mortality after severe TBI can be predicted through a mediation model with CSF cortisol and BDNF, suggesting a regulatory role for cortisol with BDNF's contribution to TBI pathophysiology and mortality, particularly among younger individuals with severe TBI. Based on the literature, cortisol modulated BDNF effects on mortality after TBI may be related to known hormone and neurotrophin relationships to neurological injury severity and autonomic nervous system imbalance. PMID:28337122

Advanced MRI in Acute Military TBI

DTIC Science & Technology

2015-11-01

advanced MRI methods, DTI and resting-state fMRI correlation analysis, in military TBI patients acutely after injury and correlate findings with TBI...14 4 Introduction The objective of the project was to test two advanced MRI methods, DTI and resting-state fMRI correlation analysis, in...of Concussion Exam (MACE )(44) were reviewed. This brief cognitive test 279 assesses orientation, immediate verbal memory , concentration, and short

Head injuries (TBI) to adults and children in motor vehicle crashes.

PubMed

Viano, David C; Parenteau, Chantal S; Xu, Likang; Faul, Mark

2017-08-18

This is a descriptive study. It determined the annual, national incidence of head injuries (traumatic brain injury, TBI) to adults and children in motor vehicle crashes. It evaluated NASS-CDS for exposure and incidence of various head injuries in towaway crashes. It evaluated 3 health databases for emergency department (ED) visits, hospitalizations, and deaths due to TBI in motor vehicle occupants. Four databases were evaluated using 1997-2010 data on adult (15+ years old) and child (0-14 years old) occupants in motor vehicle crashes: (1) NASS-CDS estimated the annual incidence of various head injuries and outcomes in towaway crashes, (2) National Hospital Ambulatory Medical Care Survey (NHAMCS)-estimated ED visits for TBI, (3) National Hospital Discharge Survey (NHDS) estimated hospitalizations for TBI, and (4) National Vital Statistics System (NVSS) estimated TBI deaths. The 4 databases provide annual national totals for TBI related injury and death in motor vehicle crashes based on differing definitions with TBI coded by the Abbreviated Injury Scale (AIS) in NASS-CDS and by International Classification of Diseases (ICD) in the health data. Adults: NASS-CDS had 16,980 ± 2,411 (risk = 0.43 ± 0.06%) with severe head injury (AIS 4+) out of 3,930,543 exposed adults in towaway crashes annually. There were 49,881 ± 9,729 (risk = 1.27 ± 0.25%) hospitalized with AIS 2+ head injury, without death. There were 6,753 ± 882 (risk = 0.17 ± 0.02%) fatalities with a head injury cause. The public health data had 89,331 ± 6,870 ED visits, 33,598 ± 1,052 hospitalizations, and 6,682 ± 22 deaths with TBI. NASS-CDS estimated 48% more hospitalized with AIS 2+ head injury without death than NHDS occupants hospitalized with TBI. NASS-CDS estimated 29% more deaths with AIS 3+ head injury than NVSS occupant TBI deaths but only 1% more deaths with a head injury cause. Children: NASS-CDS had 1,453 ± 318 (risk = 0.32 ± 0.07%) with severe head injury (AIS 4+) out of 454,973 exposed

Automated Comprehensive Evaluation of mTBI Visual Dysfunction

DTIC Science & Technology

2016-10-01

of this study is to validate the Neuro-Ophthalmic Device (NODe) test battery that provides the highest sensitivity and specificity for the detection...that the tests within the NODe test battery can serve as objective biomarkers for acute mTBI. Two hundred acute mTBI (≤72 hrs post injury) and 200 age...post-mTBI-related vision problems. The purpose of this study is to validate the Neuro-Ophthalmic Device (NODe) test battery that provides the

Combat veterans with PTSD after mild TBI exhibit greater ERPs from posterior-medial cortical areas while appraising facial features.

PubMed

Shu, I-Wei; Onton, Julie A; Prabhakar, Nitin; O'Connell, Ryan M; Simmons, Alan N; Matthews, Scott C

2014-02-01

Posttraumatic stress disorder (PTSD) worsens prognosis following mild traumatic brain injury (mTBI). Combat personnel with histories of mTBI exhibit abnormal activation of distributed brain networks-including emotion processing and default mode networks. How developing PTSD further affects these abnormalities has not been directly examined. We recorded electroencephalography in combat veterans with histories of mTBI, but without active PTSD (mTBI only, n=16) and combat veterans who developed PTSD after mTBI (mTBI+PTSD, n=16)-during the Reading the Mind in the Eyes Test (RMET), a validated test of empathy requiring emotional appraisal of facial features. Task-related event related potentials (ERPs) were identified, decomposed using independent component analysis (ICA) and localized anatomically using dipole modeling. We observed larger emotional face processing ERPs in veterans with mTBI+PTSD, including greater N300 negativity. Furthermore, greater N300 negativity correlated with greater PTSD severity, especially avoidance/numbing and hyperarousal symptom clusters. This correlation was dependent on contributions from the precuneus and posterior cingulate cortex (PCC). Our results support a model where, in combat veterans with histories of mTBI, larger ERPs from over-active posterior-medial cortical areas may be specific to PTSD, and is likely related to negative self-referential activity. © 2013 Published by Elsevier B.V.

Autobiographical memory and structural brain changes in chronic phase TBI.

PubMed

Esopenko, Carrie; Levine, Brian

2017-04-01

Traumatic brain injury (TBI) is associated with a range of neuropsychological deficits, including attention, memory, and executive functioning attributable to diffuse axonal injury (DAI) with accompanying focal frontal and temporal damage. Although the memory deficit of TBI has been well characterized with laboratory tests, comparatively little research has examined retrograde autobiographical memory (AM) at the chronic phase of TBI, with no prior studies of unselected patients drawn directly from hospital admissions for trauma. Moreover, little is known about the effects of TBI on canonical episodic and non-episodic (e.g., semantic) AM processes. In the present study, we assessed the effects of chronic-phase TBI on AM in patients with focal and DAI spanning the range of TBI severity. Patients and socioeconomic- and age-matched controls were administered the Autobiographical Interview (AI) (Levine, Svoboda, Hay, Winocur, & Moscovitch, 2002) a widely used method for dissociating episodic and semantic elements of AM, along with tests of neuropsychological and functional outcome. Measures of episodic and non-episodic AM were compared with regional brain volumes derived from high-resolution structural magnetic resonance imaging (MRI). Severe TBI (but not mild or moderate TBI) was associated with reduced recall of episodic autobiographical details and increased recall of non-episodic details relative to healthy comparison participants. There were no significant associations between AM performance and neuropsychological or functional outcome measures. Within the full TBI sample, autobiographical episodic memory was associated with reduced volume distributed across temporal, parietal, and prefrontal regions considered to be part of the brain's AM network. These results suggest that TBI-related distributed volume loss affects episodic autobiographical recollection. Copyright © 2017 Elsevier Ltd. All rights reserved.

Serum metabolites associate with CT findings following TBI.

PubMed

Dickens, Alex Mountfort; Posti, Jussi P; Takala, Riikka Sk; Ala-Seppälä, Henna Maria; Mattila, Ismo; Coles, Jonathan Coles; Frantzén, Janek; Hutchinson, Peter John; Katila, Ari J; Kyllönen, Anna; Maanpää, Henna-Riikka; Newcombe, Virginia; Outtrim, Joanne; Tallus, Jussi; Carpenter, Keri; Menon, David; Hyotylainen, Tuulia; Tenovuo, Olli; Oresic, Matej

2018-06-27

There is a need to rapidly detect patients with traumatic brain injury (TBI) who require head computed tomography (CT). Given the energy crisis in the brain following TBI, we hypothesized that serum metabolomics would be a useful tool for developing a set of biomarkers to determine the need for CT and to distinguish between different types of injuries observed. Logistic regression models using metabolite data from the discovery cohort (n=144, Turku, Finland) were used to distinguish between patients with traumatic intracranial findings and negative findings on head CT. The resultant models were then tested in the validation cohort (n=66, Cambridge, UK). The levels of glial fibrillary acidic protein and ubiquitin C-terminal hydrolase-L1 were also quantified in the serum from the same patients. Despite there being significant differences in the protein biomarkers in patients with TBI, the model that determined the need for a CT scan validated poorly (AUC=0.64: Cambridge patients). However, using a combination of six metabolites (two amino acids, three sugar derivatives and one ketoacid) it was possible to discriminate patients with intracranial abnormalities on CT and patients with a normal CT (AUC=0.77 in Turku patients and AUC=0.73 in Cambridge patients). Furthermore, a combination of three metabolites could distinguish between diffuse brain injuries and mass lesions (AUC=0.87 in Turku patients and AUC=0.68 in Cambridge patients). This study identifies a set of validated serum polar metabolites, which associate with the need for a CT scan. Additionally, serum metabolites can also predict the nature of the brain injury. These metabolite markers may prevent unnecessary CT scans, thus reducing the cost of diagnostics and radiation load.

Role of metabolomics in TBI research

PubMed Central

Wolahan, Stephanie M.; Hirt, Daniel; Braas, Daniel; Glenn, Thomas C.

2016-01-01

Synopsis Metabolomics is an important member of the omics community in that it defines which small molecules may be responsible for disease states. This article reviews the essential principles of metabolomics from specimen preparation, chemical analysis, and advanced statistical methods. Metabolomics in TBI has so far been underutilized. Future metabolomics based studies focused on the diagnoses, prognoses, and treatment effects, need to be conducted across all types of TBI. PMID:27637396

Airmen with mild traumatic brain injury (mTBI) at increased risk for subsequent mishaps.

PubMed

Whitehead, Casserly R; Webb, Timothy S; Wells, Timothy S; Hunter, Kari L

2014-02-01

Little is known regarding long-term performance decrements associated with mild Traumatic Brain Injury (mTBI). The goal of this study was to determine if individuals with an mTBI may be at increased risk for subsequent mishaps. Cox proportional hazards modeling was utilized to calculate hazard ratios for 518,958 active duty U.S. Air Force service members (Airmen) while controlling for varying lengths of follow-up and potentially confounding variables. Two non-mTBI comparison groups were used; the second being a subset of the original, both without head injuries two years prior to study entrance. Hazard ratios indicate that the causes of increased risk associated with mTBI do not resolve quickly. Additionally, outpatient mTBI injuries do not differ from other outpatient bodily injuries in terms of subsequent injury risk. These findings suggest that increased risk for subsequent mishaps are likely due to differences shared among individuals with any type of injury, including risk-taking behaviors, occupations, and differential participation in sports activities. Therefore, individuals who sustain an mTBI or injury have a long-term risk of additional mishaps. Differences shared among those who seek medical care for injuries may include risk-taking behaviors (Cherpitel, 1999; Turner & McClure, 2004; Turner, McClure, & Pirozzo, 2004), occupations, and differential participation in sports activities, among others. Individuals with an mTBI should be educated that they are at risk for subsequent injury. Historical data supported no lingering effects of mTBI, but more recent data suggest longer lasting effects. This study further adds that one of the longer term sequelae of mTBI may be an increased risk for subsequent mishap. Copyright © 2013 National Safety Council and Elsevier Ltd. All rights reserved.

Labelling Facial Affect in Context in Adults with and without TBI

PubMed Central

Turkstra, Lyn S.; Kraning, Sarah G.; Riedeman, Sarah K.; Mutlu, Bilge; Duff, Melissa; VanDenHeuvel, Sara

2017-01-01

Recognition of facial affect has been studied extensively in adults with and without traumatic brain injury (TBI), mostly by asking examinees to match basic emotion words to isolated faces. This method may not capture affect labelling in everyday life when faces are in context and choices are open-ended. To examine effects of context and response format, we asked 148 undergraduate students to label emotions shown on faces either in isolation or in natural visual scenes. Responses were categorised as representing basic emotions, social emotions, cognitive state terms, or appraisals. We used students’ responses to create a scoring system that was applied prospectively to five men with TBI. In both groups, over 50% of responses were neither basic emotion words nor synonyms, and there was no significant difference in response types between faces alone vs. in scenes. Adults with TBI used labels not seen in students’ responses, talked more overall, and often gave multiple labels for one photo. Results suggest benefits of moving beyond forced-choice tests of faces in isolation to fully characterise affect recognition in adults with and without TBI. PMID:29093643

What Are Common Traumatic Brain Injury (TBI) Symptoms?

MedlinePlus

... NICHD Research Information Find a Study More Information Traumatic Brain Injury (TBI) Condition Information NICHD Research Information Find a ... Care Providers Home Health A to Z List Traumatic Brain Injury (TBI) Condition Information What are common symptoms? Share ...

Technology and its role in rehabilitation for people with cognitive-communication disability following a traumatic brain injury (TBI).

PubMed

Brunner, Melissa; Hemsley, Bronwyn; Togher, Leanne; Palmer, Stuart

2017-01-01

To review the literature on communication technologies in rehabilitation for people with a traumatic brain injury (TBI), and: (a) determine its application to cognitive-communicative rehabilitation, and b) develop a model to guide communication technology use with people after TBI. This integrative literature review of communication technology in TBI rehabilitation and cognitive-communication involved searching nine scientific databases and included 95 studies. Three major types of communication technologies (assistive technology, augmentative and alternative communication technology, and information communication technology) and multiple factors relating to use of technology by or with people after TBI were categorized according to: (i) individual needs, motivations and goals; (ii) individual impairments, activities, participation and environmental factors; and (iii) technologies. While there is substantial research relating to communication technologies and cognitive rehabilitation after TBI, little relates specifically to cognitive-communication rehabilitation. Further investigation is needed into the experiences and views of people with TBI who use communication technologies, to provide the 'user' perspective and influence user-centred design. Research is necessary to investigate the training interventions that address factors fundamental for success, and any impact on communication. The proposed model provides an evidence-based framework for incorporating technology into speech pathology clinical practice and research.

PTSD-Related Behavioral Traits in a Rat Model of Blast-Induced mTBI Are Reversed by the mGluR2/3 Receptor Antagonist BCI-838.

PubMed

Perez-Garcia, Georgina; De Gasperi, Rita; Gama Sosa, Miguel A; Perez, Gissel M; Otero-Pagan, Alena; Tschiffely, Anna; McCarron, Richard M; Ahlers, Stephen T; Elder, Gregory A; Gandy, Sam

2018-01-01

Battlefield blast exposure related to improvised explosive devices (IEDs) has become the most common cause of traumatic brain injury (TBI) in the recent conflicts in Iraq and Afghanistan. Mental health problems are common after TBI. A striking feature in the most recent veterans has been the frequency with which mild TBI (mTBI) and posttraumatic stress disorder (PTSD) have appeared together, in contrast to the classical situations in which the presence of mTBI has excluded the diagnosis of PTSD. However, treatment of PTSD-related symptoms that follow blast injury has become a significant problem. BCI-838 (MGS0210) is a Group II metabotropic glutamate receptor (mGluR2/3) antagonist prodrug, and its active metabolite BCI-632 (MGS0039) has proneurogenic, procognitive, and antidepressant activities in animal models. In humans, BCI-838 is currently in clinical trials for refractory depression and suicidality. The aim of the current study was to determine whether BCI-838 could modify the anxiety response and reverse PTSD-related behaviors in rats exposed to a series of low-level blast exposures designed to mimic a human mTBI or subclinical blast exposure. BCI-838 treatment reversed PTSD-related behavioral traits improving anxiety and fear-related behaviors as well as long-term recognition memory. Treatment with BCI-838 also increased neurogenesis in the dentate gyrus (DG) of blast-exposed rats. The safety profile of BCI-838 together with the therapeutic activities reported here, make BCI-838 a promising drug for the treatment of former battlefield Warfighters suffering from PTSD-related symptoms following blast-induced mTBI.

PTSD-Related Behavioral Traits in a Rat Model of Blast-Induced mTBI Are Reversed by the mGluR2/3 Receptor Antagonist BCI-838

PubMed Central

Perez-Garcia, Georgina; De Gasperi, Rita; Gama Sosa, Miguel A.; Perez, Gissel M.; Otero-Pagan, Alena; Tschiffely, Anna; McCarron, Richard M.; Ahlers, Stephen T.

2018-01-01

Battlefield blast exposure related to improvised explosive devices (IEDs) has become the most common cause of traumatic brain injury (TBI) in the recent conflicts in Iraq and Afghanistan. Mental health problems are common after TBI. A striking feature in the most recent veterans has been the frequency with which mild TBI (mTBI) and posttraumatic stress disorder (PTSD) have appeared together, in contrast to the classical situations in which the presence of mTBI has excluded the diagnosis of PTSD. However, treatment of PTSD-related symptoms that follow blast injury has become a significant problem. BCI-838 (MGS0210) is a Group II metabotropic glutamate receptor (mGluR2/3) antagonist prodrug, and its active metabolite BCI-632 (MGS0039) has proneurogenic, procognitive, and antidepressant activities in animal models. In humans, BCI-838 is currently in clinical trials for refractory depression and suicidality. The aim of the current study was to determine whether BCI-838 could modify the anxiety response and reverse PTSD-related behaviors in rats exposed to a series of low-level blast exposures designed to mimic a human mTBI or subclinical blast exposure. BCI-838 treatment reversed PTSD-related behavioral traits improving anxiety and fear-related behaviors as well as long-term recognition memory. Treatment with BCI-838 also increased neurogenesis in the dentate gyrus (DG) of blast-exposed rats. The safety profile of BCI-838 together with the therapeutic activities reported here, make BCI-838 a promising drug for the treatment of former battlefield Warfighters suffering from PTSD-related symptoms following blast-induced mTBI. PMID:29387781

TBI-ROC Part One: Understanding Traumatic Brain Injury--An Introduction

ERIC Educational Resources Information Center

Trudel, Tina M.; Scherer, Marcia J.; Elias, Eileen

2011-01-01

This article is the first of a multi-part series on traumatic brain injury (TBI). Historically, TBI has received very limited national public policy attention and support. However since it has become the signature injury of the military conflicts in Iraq and Afghanistan, TBI has gained the attention of elected officials, military leaders,…

Mission Connect Mild TBI Translational Research Consortium

DTIC Science & Technology

2009-08-01

is to identify the incidence of post traumatic hypopituitarism (PTH) in mild TBI and develop criteria for assessing which patients with a mild TBI are...Introduction: The purpose of this project will be to study the diagnosis of post traumatic hypopituitarism after MTBI. We will determine the incidence...of hypopituitarism following MTBI and develop criteria for assessing which MTBI patients are at high risk for developing posttraumatic

An audit of traumatic brain injury (TBI) in a busy developing-world trauma service exposes a significant deficit in resources available to manage severe TBI.

PubMed

Jerome, Ellen; Laing, Grant L; Bruce, John L; Sartorius, Ben; Brysiewicz, Petra; Clarke, Damian L

2017-06-30

Traumatic brain injury (TBI) affects large numbers of patients, both adults and children, and significant resources are needed to manage it. To determine the burden of TBI and the adequacy of available resources to manage in the Pietermaritzburg Metropolitan Trauma Service (PMTS). All patients with a TBI were identified from the hybrid electronic medical registry at Grey's and Edendale hospitals in Pietermaritzburg (PMB), KwaZulu-Natal, South Africa. Patients were classified according to severity of head injury and age. We defined mild TBI as Glasgow coma scale (GCS) 13 - 15, moderate as GCS 9 - 12, and severe as GCS ≤8, in accordance with international standards. We divided the cohort according to ages 0 - 5 years, 6 - 10 years, >10 - 17 years and adults (>17 years). From January 2012 to December 2014, 3 301 patients were treated for TBI in PMB. The mean age was 27.4 (standard deviation 14.4) years. There were 2 632 males and 564 females. There were 2 540 mild, 326 moderate, and 329 severe TBI admissions during the period under review. A total of 139 (4.2%) patients died. A total of 242 (7.3%) patients were admitted to the intensive care unit (ICU), of whom 137 (57.0%) had a GCS of ≤9. Only 27.0% of patients with a GCS of ≤9 were admitted to the ICU. There is a significant burden of TBI managed by the PMTS. Critical care resources available to manage patients with TBI are inadequate.

Structural white matter differences underlying heterogeneous learning abilities after TBI.

PubMed

Chiou, Kathy S; Genova, Helen M; Chiaravalloti, Nancy D

2016-12-01

The existence of learning deficits after traumatic brain injury (TBI) is generally accepted; however, our understanding of the structural brain mechanisms underlying learning impairment after TBI is limited. Furthermore, our understanding of learning after TBI is often at risk for overgeneralization, as research often overlooks within sample heterogeneity in learning abilities. The present study examined differences in white matter integrity in a sample of adults with moderate to severe TBI who differed in learning abilities. Adults with moderate to severe TBI were grouped into learners and non-learners based upon achievement of the learning criterion of the open-trial Selective Reminding Test (SRT). Diffusion tensor imaging (DTI) was used to identify white matter differences between the learners and non-learners. Adults with TBI who were able to meet the learning criterion had greater white matter integrity (as indicated by higher fractional anisotropy [FA] values) in the right anterior thalamic radiation, forceps minor, inferior fronto-occipital fasciculus, and forceps minor than non-learners. The results of the study suggest that differences in white matter integrity may explain the observed heterogeneity in learning ability after moderate to severe TBI. This also supports emerging evidence for the involvement of the thalamus in higher order cognition, and the role of thalamo-cortical tracts in connecting functional networks associated with learning.

Legacy Clinical Data from the Epo TBI Trial

DTIC Science & Technology

2016-06-01

investigators through the Federal Interagency Traumatic Brain Injury (FITBIR) Informatics System. This trial was funded by National Institute of Neurological...Effects of Erythropoietin (Epo) on Cerebral Vascular Dysfunction and Anemia in Traumatic Brain Injury (TBI)” which we will share with other...the format required by FITBIR. 2. KEYWORDS: Traumatic brain injury Erythropoietin Anemia Transfusion threshold 3. ACCOMPLISHMENTS: What

Neuroprotective effect of acute ethanol intoxication in TBI is associated to the hierarchical modulation of early transcriptional responses.

PubMed

Chandrasekar, Akila; Aksan, Bahar; Heuvel, Florian Olde; Förstner, Philip; Sinske, Daniela; Rehman, Rida; Palmer, Annette; Ludolph, Albert; Huber-Lang, Markus; Böckers, Tobias; Mauceri, Daniela; Knöll, Bernd; Roselli, Francesco

2018-04-01

Ethanol intoxication is a risk factor for traumatic brain injury (TBI) but clinical evidence suggests that it may actually improve the prognosis of intoxicated TBI patients. We have employed a closed, weight-drop TBI model of different severity (2cm or 3cm falling height), preceded (-30min) or followed (+20min) by ethanol administration (5g/Kg). This protocol allows us to study the interaction of binge ethanol intoxication in TBI, monitoring behavioral changes, histological responses and the transcriptional regulation of a series of activity-regulated genes (immediate early genes, IEGs). We demonstrate that ethanol pretreatment before moderate TBI (2cm) significantly reduces neurological impairment and accelerates recovery. In addition, better preservation of neuronal numbers and cFos+cells was observed 7days after TBI. At transcriptional level, ethanol reduced the upregulation of a subset of IEGs encoding for transcription factors such as Atf3, c-Fos, FosB, Egr1, Egr3 and Npas4 but did not affect the upregulation of others (e.g. Gadd45b and Gadd45c). While a subset of IEGs encoding for effector proteins (such as Bdnf, InhbA and Dusp5) were downregulated by ethanol, others (such as Il-6) were unaffected. Notably, the majority of genes were sensitive to ethanol only when administered before TBI and not afterwards (the exceptions being c-Fos, Egr1 and Dusp5). Furthermore, while severe TBI (3cm) induced a qualitatively similar (but quantitatively larger) transcriptional response to moderate TBI, it was no longer sensitive to ethanol pretreatment. Thus, we have shown that a subset of the TBI-induced transcriptional responses were sensitive to ethanol intoxication at the instance of trauma (ultimately resulting in beneficial outcomes) and that the effect of ethanol was restricted to a certain time window (pre TBI treatment) and to TBI severity (moderate). This information could be critical for the translational value of ethanol in TBI and for the design of clinical

Balancing act: the influence of adaptability and cohesion on satisfaction and communication in families facing TBI in Mexico.

PubMed

Lehan, Tara J; Stevens, Lillian Flores; Arango-Lasprilla, Juan Carlos; Díaz Sosa, Dulce María; Espinosa Jove, Irma Guadalupe

2012-01-01

Much of what is known about family functioning in the face of traumatic brain injury (TBI) is based on research conducted in the United States. The purpose of this study was to (1) describe the levels of family adaptability, cohesion, communication, and satisfaction as reported by Mexican TBI survivors and their family caregivers, (2) test the hypothesis of the Circumplex Model that balanced families would exhibit better communication and greater satisfaction, and (3) explore how TBI survivors' and their family caregivers' perceptions of family adaptability and cohesion influenced their own and the other's perceptions of family communication and satisfaction. In the majority of dyads, both the TBI survivor and the family caregiver endorsed balanced family adaptability and cohesion. Both TBI survivors and their family caregivers reported a relatively high level of family communication and satisfaction. TBI survivors and family caregivers who reported greater levels of family adaptability and cohesion also endorsed better family communication and greater family satisfaction. In addition, individuals with TBI whose family caregiver endorsed balanced family adaptability and cohesion reported better family communication. Further, family caregivers of TBI survivors who reported balanced family adaptability and cohesion reported better family communication. Implications for research and practice are discussed.

EYE-TRAC: monitoring attention and utility for mTBI

NASA Astrophysics Data System (ADS)

Maruta, Jun; Tong, Jianliang; Lee, Stephanie W.; Iqbal, Zarah; Schonberger, Alison; Ghajar, Jamshid

2012-06-01

Attention is a core function in cognition and also the most prevalent cognitive deficit in mild traumatic brain injury (mTBI). Predictive timing is an essential element of attention functioning because sensory processing and execution of goal-oriented behavior are facilitated by temporally accurate prediction. It is hypothesized that impaired synchronization between prediction and external events accounts for the attention deficit in mTBI. Other cognitive and somatic or affective symptoms associated with mTBI may be explained as secondary consequences of impaired predictive timing. Eye-Tracking Rapid Attention Computation (EYE-TRAC) is the quantification of predictive timing with indices of dynamic visuo-motor synchronization (DVS) between the gaze and the target during continuous predictive visual tracking. Such quantification allows for cognitive performance monitoring in comparison to the overall population as well as within individuals over time. We report preliminary results of normative data and data collected from subjects with a history of mTBI within 2 weeks of injury and post-concussive symptoms at the time of recruitment. A substantial proportion of mTBI subjects demonstrated DVS scores worse than 95% of normal subjects. In addition, longitudinal monitoring of acute mTBI subjects showed that initially abnormal DVS scores were followed by improvement toward the normal range. In summary, EYE-TRAC provides fast and objective indices of DVS that allow comparison of attention performance to a normative standard and monitoring of within-individual changes.

Mission Connect Mild TBI Translational Research Consortium

DTIC Science & Technology

2014-08-01

outcome. At 6 months post injury, patients will be screened for anterior pituitary function f the 61 mTBI subjects with IGF-1 results at the 6 month... anterior pituitary function, including somatomedin (IGF-1), thyroid stimulating hormone (TSH), thyroxine (Free T4), prolactin, and total cortisol in...resolution of PCS at six months after mTBI. We will also examine the incidence of single and multiple pituitary hormone deficiencies. The clinical

Mission Connect Mild TBI Translational Research Consortium

DTIC Science & Technology

2013-08-01

injury, patients will be screened for anterior pituitary function of the 56 mTBI subjects with IGF-1 results, of the 63 who completed the 6 month... anterior pituitary function, including somatomedin (IGF -1 ), thyroid stimulating hormone (TSH), thyroxine (Free T4), prolactin, and total cortisol in all...resolution of PCS at six months after mTBI. We will also examine the incidence of single and multiple pituitary hormone deficiencies. The clinical

Mission Connect Mild TBI Translational Research Consortium

DTIC Science & Technology

2010-08-01

Grill RJ, Parsley MA, Unabia G, Hulsebosch CE. Anti- inflammatory treatment of traumatic brain injury (TBI). Society for Neuroscience, 2009...Hulsebosch, CD, DeWitt DS, Dash PK, Grill RJ, Parsley MA, Unabia, BC, Rea HC, & Perez-Polo, JR Role of IL-1 and TNF receptor activation in neurological...deficits at TBI. Military health Research Forum, 2009. Hulsebosch, CD, DeWitt DS, Dash PK, Grill RJ, Parsley MA, Unabia, BC, Rea HC, & Perez-Polo, JR

Chronic neuropathologies of single and repetitive TBI: substrates of dementia?

PubMed Central

Smith, Douglas H.; Johnson, Victoria E.; Stewart, William

2014-01-01

Traumatic brain injury (TBI) has long been recognized to be a risk factor for dementia. This association has, however, only recently gained widespread attention through the increased awareness of ‘chronic traumatic encephalopathy’ (CTE) in athletes exposed to repetitive head injury. Originally termed ‘dementia pugilistica’ and linked to a career in boxing, descriptions of the neuropathological features of CTE include brain atrophy, cavum septum pellucidum, and amyloid-β, tau and TDP-43 pathologies, many of which might contribute to clinical syndromes of cognitive impairment. Similar chronic pathologies are also commonly found years after just a single moderate to severe TBI. However, little consensus currently exists on specific features of these post-TBI syndromes that might permit their confident clinical and/or pathological diagnosis. Moreover, the mechanisms contributing to neurodegeneration following TBI largely remain unknown. Here, we review the current literature and controversies in the study of chronic neuropathological changes after TBI. PMID:23458973

Parallel Human and Animal Models of Blast- and Concussion-Induced Tinnitus and Related Traumatic Brain Injury (TBI)

DTIC Science & Technology

2013-01-01

supportive apparatus with a locking mechanism . The blast was delivered at approximately 14 and 22 PSI, which generated a noise of 10 ms duration at ~194...Rats were sacrificed two weeks after TBI for histological observations of axonal injury. Data. No skull fractures , respiratory depression or...Mark Haacke, and Pamela VandeVord (2012) Mechanisms and Treatment Strategies of Blast-Induced Tinnitus and Its Related TBI. Military Health 62 | P a

Detection of Subtle Cognitive Changes after mTBI Using a Novel Tablet-Based Task.

PubMed

Fischer, Tara D; Red, Stuart D; Chuang, Alice Z; Jones, Elizabeth B; McCarthy, James J; Patel, Saumil S; Sereno, Anne B

2016-07-01

This study examined the potential for novel tablet-based tasks, modeled after eye tracking techniques, to detect subtle sensorimotor and cognitive deficits after mild traumatic brain injury (mTBI). Specifically, we examined whether performance on these tablet-based tasks (Pro-point and Anti-point) was able to correctly categorize concussed versus non-concussed participants, compared with performance on other standardized tests for concussion. Patients admitted to the emergency department with mTBI were tested on the Pro-point and Anti-point tasks, a current standard cognitive screening test (i.e., the Standard Assessment of Concussion [SAC]), and another eye movement-based tablet test, the King-Devick(®) (KD). Within hours after injury, mTBI patients showed significant slowing in response times, compared with both orthopedic and age-matched control groups, in the Pro-point task, demonstrating deficits in sensorimotor function. Mild TBI patients also showed significant slowing, compared with both control groups, on the Anti-point task, even when controlling for sensorimotor slowing, indicating deficits in cognitive function. Performance on the SAC test revealed similar deficits of cognitive function in the mTBI group, compared with the age-matched control group; however, the KD test showed no evidence of cognitive slowing in mTBI patients, compared with either control group. Further, measuring the sensitivity and specificity of these tasks to accurately predict mTBI with receiver operating characteristic analysis indicated that the Anti-point and Pro-point tasks reached excellent levels of accuracy and fared better than current standardized tools for assessment of concussion. Our findings suggest that these rapid tablet-based tasks are able to reliably detect and measure functional impairment in cognitive and sensorimotor control within hours after mTBI. These tasks may provide a more sensitive diagnostic measure for functional deficits that could prove key to

Detection of Subtle Cognitive Changes after mTBI Using a Novel Tablet-Based Task

PubMed Central

Red, Stuart D.; Chuang, Alice Z.; Jones, Elizabeth B.; McCarthy, James J.; Patel, Saumil S.; Sereno, Anne B.

2016-01-01

Abstract This study examined the potential for novel tablet-based tasks, modeled after eye tracking techniques, to detect subtle sensorimotor and cognitive deficits after mild traumatic brain injury (mTBI). Specifically, we examined whether performance on these tablet-based tasks (Pro-point and Anti-point) was able to correctly categorize concussed versus non-concussed participants, compared with performance on other standardized tests for concussion. Patients admitted to the emergency department with mTBI were tested on the Pro-point and Anti-point tasks, a current standard cognitive screening test (i.e., the Standard Assessment of Concussion [SAC]), and another eye movement–based tablet test, the King-Devick® (KD). Within hours after injury, mTBI patients showed significant slowing in response times, compared with both orthopedic and age-matched control groups, in the Pro-point task, demonstrating deficits in sensorimotor function. Mild TBI patients also showed significant slowing, compared with both control groups, on the Anti-point task, even when controlling for sensorimotor slowing, indicating deficits in cognitive function. Performance on the SAC test revealed similar deficits of cognitive function in the mTBI group, compared with the age-matched control group; however, the KD test showed no evidence of cognitive slowing in mTBI patients, compared with either control group. Further, measuring the sensitivity and specificity of these tasks to accurately predict mTBI with receiver operating characteristic analysis indicated that the Anti-point and Pro-point tasks reached excellent levels of accuracy and fared better than current standardized tools for assessment of concussion. Our findings suggest that these rapid tablet-based tasks are able to reliably detect and measure functional impairment in cognitive and sensorimotor control within hours after mTBI. These tasks may provide a more sensitive diagnostic measure for functional deficits that could prove

Neurologic Functional and Quality of Life Outcomes after TBI: Clinic Attendees versus Non-Attendees.

PubMed

Patel, Mayur B; Wilson, Laura D; Bregman, Jana A; Leath, Taylor C; Humble, Stephen S; Davidson, Mario A; de Riesthal, Michael R; Guillamondegui, Oscar D

2015-07-01

This investigation describes the relationship between TBI patient demographics, quality of life outcome, and functional status outcome among clinic attendees and non-attendees. Of adult TBI survivors with intracranial hemorrhage, 63 attended our TBI clinic and 167 did not attend. All were telephone surveyed using the Extended-Glasgow Outcome Scale (GOSE), the Quality of Life after Brain Injury (QOLIBRI) scale, and a post-discharge therapy questionnaire. To determine risk factors for GOSE and QOLIBRI outcomes, we created multivariable regression models employing covariates of age, injury characteristics, clinic attendance, insurance status, post-discharge rehabilitation, and time from injury. Compared with those with severe TBI, higher GOSE scores were identified in individuals with both mild (odds ratio [OR]=2.0; 95% confidence interval [CI]: 1.1-3.6) and moderate (OR=4.7; 95% CI: 1.6-14.1) TBIs. In addition, survivors with private insurance had higher GOSE scores, compared with those with public insurance (OR=2.0; 95% CI: 1.1-3.6), workers' compensation (OR=8.4; 95% CI: 2.6-26.9), and no insurance (OR=3.1; 95% CI: 1.6-6.2). Compared with those with severe TBI, QOLIBRI scores were 11.7 points (95% CI: 3.7-19.7) higher in survivors with mild TBI and 17.3 points (95% CI: 3.2-31.5) higher in survivors with moderate TBI. In addition, survivors who received post-discharge rehabilitation had higher QOLIBRI scores by 11.4 points (95% CI: 3.7-19.1) than those who did not. Survivors with private insurance had QOLIBRI scores that were 25.5 points higher (95% CI: 11.3-39.7) than those with workers' compensation and 16.8 points higher (95% CI: 7.4-26.2) than those without insurance. Because neurologic injury severity, insurance status, and receipt of rehabilitation or therapy are independent risk factors for functional and quality of life outcomes, future directions will include improving earlier access to post-TBI rehabilitation, social work services, affordable insurance

Legacy Clinical Data from the Mission Connect Mild TBI Translational Research Consortium

DTIC Science & Technology

2017-10-01

mTBI) Translational Research Consortium was to improve the diagnosis and treatment of mTBI. We enrolled a total of 88 mTBI patients and 73 orthopedic ...AWARD NUMBER: W81XWH-16-2-0026 TITLE: Legacy Clinical Data from the Mission Connect Mild TBI Translational Research Consortium PRINCIPAL...Annual PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 DISTRIBUTION STATEMENT: Approved for

Peroxiredoxin VI Oxidation in Cerebrospinal Fluid Correlates with TBI Outcome

PubMed Central

Manevich, Y.; Hutchens, S.; Halushka, P.V.; Tew, K.D.; Townsend, D. M.; Jauch, E.C.; Borg, K.

2014-01-01

Traumatic brain injury (TBI) patients would benefit from the identification of reliable biomarkers to predict outcomes and treatment strategies. In our study, cerebrospinal fluid (CSF) from patients with severe TBI was evaluated for oxidant stress-mediated damage progression after hospital admission and subsequent ventriculostomy placement. Interestingly, substantial levels of peroxiredoxin VI (Prdx6), a major antioxidant enzyme normally found in astrocytes, were detected in CSF from control and TBI patients, and were not associated with blood contamination. Functionally, Prdx6 and its associated binding partner glutathione S-transferase pi (GSTP1-1, also detected in CSF) act in tandem to detoxify lipid peroxidation damage to membranes. We found Prdx6 was fully active in CSF of control patients but becomes significantly inactivated (oxidized) under TBI. Furthermore, significant and progressive oxidation of “buried” protein thiol in CSF of TBI patients (as compared to that of non-trauma control) were detected over a 24h period following hospital admission, with increased oxidation correlating with severity of trauma. Conversely, recovery of Prdx6 activity after 24h indicated more favorable patient outcome. Not only is this the first report of an extracellular form of Prdx6 but also the first report of its detection at a substantial level in CSF. Taken together, our data suggest a meaningful correlation between TBI-initiated oxidation of Prdx6, its specific phospholipid hydroperoxide peroxidase activity, and severity of trauma outcome. Consequently, we propose that Prdx6 redox status detection has the potential to be a biomarker for TBI outcome and a future indicator of therapeutic efficacy. PMID:24726861

Early detection of subclinical visual damage after blast-mediated TBI enables prevention of chronic visual deficit by treatment with P7C3-S243.

PubMed

Dutca, Laura M; Stasheff, Steven F; Hedberg-Buenz, Adam; Rudd, Danielle S; Batra, Nikhil; Blodi, Frederick R; Yorek, Matthew S; Yin, Terry; Shankar, Malini; Herlein, Judith A; Naidoo, Jacinth; Morlock, Lorraine; Williams, Noelle; Kardon, Randy H; Anderson, Michael G; Pieper, Andrew A; Harper, Matthew M

2014-12-02

Traumatic brain injury (TBI) frequently leads to chronic visual dysfunction. The purpose of this study was to investigate the effect of TBI on retinal ganglion cells (RGCs), and to test whether treatment with the novel neuroprotective compound P7C3-S243 could prevent in vivo functional deficits in the visual system. Blast-mediated TBI was modeled using an enclosed over-pressure blast chamber. The RGC physiology was evaluated using a multielectrode array and pattern electroretinogram (PERG). Histological analysis of RGC dendritic field and cell number were evaluated at the end of the study. Visual outcome measures also were evaluated based on treatment of mice with P7C3-S243 or vehicle control. We show that deficits in neutral position PERG after blast-mediated TBI occur in a temporally bimodal fashion, with temporary recovery 4 weeks after injury followed by chronically persistent dysfunction 12 weeks later. This later time point is associated with development of dendritic abnormalities and irreversible death of RGCs. We also demonstrate that ongoing pathologic processes during the temporary recovery latent period (including abnormalities of RGC physiology) lead to future dysfunction of the visual system. We report that modification of PERG to provocative postural tilt testing elicits changes in PERG measurements that correlate with a key in vitro measures of damage: the spontaneous and light-evoked activity of RGCs. Treatment with P7C3-S243 immediately after injury and throughout the temporary recovery latent period protects mice from developing chronic visual system dysfunction. Provocative PERG testing serves as a noninvasive test in the living organism to identify early damage to the visual system, which may reflect corresponding damage in the brain that is not otherwise detectable by noninvasive means. This provides the basis for developing an earlier diagnostic test to identify patients at risk for developing chronic CNS and visual system damage after TBI at

Early Detection of Subclinical Visual Damage After Blast-Mediated TBI Enables Prevention of Chronic Visual Deficit by Treatment With P7C3-S243

PubMed Central

Dutca, Laura M.; Stasheff, Steven F.; Hedberg-Buenz, Adam; Rudd, Danielle S.; Batra, Nikhil; Blodi, Frederick R.; Yorek, Matthew S.; Yin, Terry; Shankar, Malini; Herlein, Judith A.; Naidoo, Jacinth; Morlock, Lorraine; Williams, Noelle; Kardon, Randy H.; Anderson, Michael G.; Pieper, Andrew A.; Harper, Matthew M.

2014-01-01

Purpose. Traumatic brain injury (TBI) frequently leads to chronic visual dysfunction. The purpose of this study was to investigate the effect of TBI on retinal ganglion cells (RGCs), and to test whether treatment with the novel neuroprotective compound P7C3-S243 could prevent in vivo functional deficits in the visual system. Methods. Blast-mediated TBI was modeled using an enclosed over-pressure blast chamber. The RGC physiology was evaluated using a multielectrode array and pattern electroretinogram (PERG). Histological analysis of RGC dendritic field and cell number were evaluated at the end of the study. Visual outcome measures also were evaluated based on treatment of mice with P7C3-S243 or vehicle control. Results. We show that deficits in neutral position PERG after blast-mediated TBI occur in a temporally bimodal fashion, with temporary recovery 4 weeks after injury followed by chronically persistent dysfunction 12 weeks later. This later time point is associated with development of dendritic abnormalities and irreversible death of RGCs. We also demonstrate that ongoing pathologic processes during the temporary recovery latent period (including abnormalities of RGC physiology) lead to future dysfunction of the visual system. We report that modification of PERG to provocative postural tilt testing elicits changes in PERG measurements that correlate with a key in vitro measures of damage: the spontaneous and light-evoked activity of RGCs. Treatment with P7C3-S243 immediately after injury and throughout the temporary recovery latent period protects mice from developing chronic visual system dysfunction. Conclusions. Provocative PERG testing serves as a noninvasive test in the living organism to identify early damage to the visual system, which may reflect corresponding damage in the brain that is not otherwise detectable by noninvasive means. This provides the basis for developing an earlier diagnostic test to identify patients at risk for developing chronic

Different quantitative EEG alterations induced by TBI among patients with different APOE genotypes.

PubMed

Jiang, Li; Yin, Xiaohong; Yin, Cheng; Zhou, Shuai; Dan, Wei; Sun, Xiaochuan

2011-11-14

Although several studies have revealed the EEG alterations in AD and TBI patients, the influence of APOE (apolipoprotein E) genotype in EEG at the early stage of TBI has not been reported yet. We have previously studied EEG alterations caused by TBI among different APOE genotype carriers. In this study, we firstly investigated the relationship between APOE polymorphisms and quantitative EEG (QEEG) changes after TBI. A total of 118 consecutive TBI patients with a Glasgow Coma Scale (GCS) of 9 or higher were recruited, and 40 normal adults were also included as a control group. APOE genotype was determined by PCR-RFLP for each subject, and QEEG recordings were performed in rest, relaxed, awake and with eyes closed in normal subjects and TBI patients during 1-3 days after TBI. In the normal control group, both APOEɛ4 carriers and non-carriers had normal EEG, and no significant difference of QEEG data was found between APOEɛ4 carriers and non-carriers. But in the TBI group, APOEɛ4 carriers had more focal or global irregular slow wave activities than APOEɛ4 non-carriers. APOE gene did not influence brain electrical activity under normal conditions, but TBI can induce different alterations among different APOE gene carriers, and APOEɛ4 allele enhances the EEG abnormalities at the early stage of TBI. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Common biochemical defects linkage between post-traumatic stress disorders, mild traumatic brain injury (TBI) and penetrating TBI.

PubMed

Prasad, Kedar N; Bondy, Stephen C

2015-03-02

Post-traumatic stress disorder (PTSD) is a complex mental disorder with psychological and emotional components, caused by exposure to single or repeated extreme traumatic events found in war, terrorist attacks, natural or man-caused disasters, and by violent personal assaults and accidents. Mild traumatic brain injury (TBI) occurs when the brain is violently rocked back and forth within the skull following a blow to the head or neck as in contact sports, or when in close proximity to a blast pressure wave following detonation of explosives in the battlefield. Penetrating TBI occurs when an object penetrates the skull and damages the brain, and is caused by vehicle crashes, gunshot wound to the head, and exposure to solid fragments in the proximity of explosions, and other combat-related head injuries. Despite clinical studies and improved understanding of the mechanisms of cellular damage, prevention and treatment strategies for patients with PTSD and TBI remain unsatisfactory. To develop an improved plan for treating and impeding progression of PTSD and TBI, it is important to identify underlying biochemical changes that may play key role in the initiation and progression of these disorders. This review identifies three common biochemical events, namely oxidative stress, chronic inflammation and excitotoxicity that participate in the initiation and progression of these conditions. While these features are separately discussed, in many instances, they overlap. This review also addresses the goal of developing novel treatments and drug regimens, aimed at combating this triad of events common to, and underlying, injury to the brain. Copyright © 2014 Elsevier B.V. All rights reserved.

Combat veterans with comorbid PTSD and mild TBI exhibit a greater inhibitory processing ERP from the dorsal anterior cingulate cortex.

PubMed

Shu, I-Wei; Onton, Julie A; O'Connell, Ryan M; Simmons, Alan N; Matthews, Scott C

2014-10-30

Posttraumatic stress disorder (PTSD) is common among combat personnel with mild traumatic brain injury (mTBI). While patients with either PTSD or mTBI share abnormal activation of multiple frontal brain areas, anterior cingulate cortex (ACC) activity during inhibitory processing may be particularly affected by PTSD. To further test this hypothesis, we recorded electroencephalography from 32 combat veterans with mTBI-17 of whom were also comorbid for PTSD (mTBI+PTSD) and 15 without PTSD (mTBI-only). Subjects performed the Stop Task, a validated inhibitory control task requiring inhibition of initiated motor responses. We observed a larger inhibitory processing eventrelated potential (ERP) in veterans with mTBI+PTSD, including greater N200 negativity. Furthermore, greater N200 negativity correlated with greater PTSD severity. This correlation was most dependent on contributions from the dorsal ACC. Support vector machine analysis demonstrated that N200 and P300 amplitudes objectively classified veterans into mTBI-only or mTBI+PTSD groups with 79.4% accuracy. Our results support a model where, in combat veterans with mTBI, larger ERPs from cingulate areas are associated with greater PTSD severity and likely related to difficulty controlling ongoing brain processes, including trauma-related thoughts and feelings. Published by Elsevier Ireland Ltd.

Proceedings of the military mTBI Diagnostics Workshop, St. Pete Beach, August 2010.

PubMed

Marion, Donald W; Curley, Kenneth C; Schwab, Karen; Hicks, Ramona R

2011-04-01

Approximately 28,000 service members (SMs) sustain a traumatic brain injury (TBI) each year in the U.S. military. The majority of the injuries result either in a brief or no loss of consciousness, and are classified as a mild TBI (mTBI or concussion). Current evaluation guidelines of SMs suspected of having a mTBI rely heavily on self-reports. However, there is concern that SMs typically minimize or do not report their symptoms of mTBI for fear that doing so will result in being removed from the battlefield. Because mTBI often results in headaches, cognitive dysfunction, attention difficulties, and balance problems, returning to the battlefield before resolution of their symptoms can be dangerous for the SM and for their unit. Sustaining a second concussion before resolution of a previous mTBI also may make long-term neuronal injury more likely. The mTBI Diagnostics Workshop was designed as a forum where civilian and military experts from a variety of TBI-related clinical and basic science disciplines could meet to define the diagnostic tools, alone or in combination, that were most likely to result in an acute, objective diagnosis of mTBI. The premise of the meeting was that a small number of well-focused research projects conducted over the next 2-3 years could be done to validate the optimal test, or more likely combination of tests, that would be practical and reliable for the acute diagnosis of mTBI within 2-3 h of injury in theater. The recommendations of the Workshop are provided in this report.

The incidence of ARDS and associated mortality in severe TBI using the Berlin definition.

PubMed

Aisiku, Imoigele P; Yamal, Jose-Miguel; Doshi, Pratik; Rubin, Maria Laura; Benoit, Julia S; Hannay, Julia; Tilley, Barbara C; Gopinath, Shankar; Robertson, Claudia S

2016-02-01

The incidence of adult respiratory distress syndrome (ARDS) in severe traumatic brain injury (TBI) is poorly reported. Recently, a new definition for ARDS was proposed, the Berlin definition. The percentage of patients represented by TBI in the Berlin criteria study is limited. This study describes the incidence and associated mortality of ARDS in TBI patients. The study was an analysis of the safety of erythropoietin administration and transfusion threshold on the incidence of ARDS in severe TBI patients. Three reviewers independently assessed all patients enrolled in the study for acute lung injury/ARDS using the Berlin and the American-European Consensus Conference (AECC) definitions. A Cox proportional hazards model was used to assess the relationship between ARDS and mortality and 6-month Glasgow Outcome Scale (GOS) score. Two hundred patients were enrolled in the study. Of the patients, 21% (41 of 200) and 26% (52 of 200) developed ARDS using the AECC and Berlin definitions, respectively, with a median time of 3 days (interquartile range, 3) after injury. ARDS by either definition was associated with increased mortality (p = 0.04) but not with differences in functional outcome as measured by the GOS score at 6 months. Adjusted analysis using the Berlin criteria showed an increased mortality associated with ADS (p = 0.01). Severe TBI is associated with an incidence of ARDS ranging from 20% to 25%. The incidence is comparable between the Berlin and AECC definitions. ARDS is associated with increased mortality in severe TBI patients, but further studies are needed to validate these findings. Epidemiologic study, level II.

Treatment of TBI and Concomitant Hemorrhage with Ghrelin

DTIC Science & Technology

2010-07-01

TITLE: Treatment of TBI and concomitant hemorrhage with ghrelin PRINCIPAL INVESTIGATOR: Rongqian Wu...TITLE AND SUBTITLE Treatment of TBI and concomitant hemorrhage with ghrelin 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT...would be a powerful tool to improve outcome after brain injury. Ghrelin is a ‘gut-brain’ hormone mostly produced by the stomach. In this project, we

Functional neuroimaging with default mode network regions distinguishes PTSD from TBI in a military veteran population.

PubMed

Raji, Cyrus A; Willeumier, Kristen; Taylor, Derek; Tarzwell, Robert; Newberg, Andrew; Henderson, Theodore A; Amen, Daniel G

2015-09-01

PTSD and TBI are two common conditions in veteran populations that can be difficult to distinguish clinically. The default mode network (DMN) is abnormal in a multitude of neurological and psychiatric disorders. We hypothesize that brain perfusion SPECT can be applied to diagnostically separate PTSD from TBI reliably in a veteran cohort using DMN regions. A group of 196 veterans (36 with PTSD, 115 with TBI, 45 with PTSD/TBI) were selected from a large multi-site population cohort of individuals with psychiatric disease. Inclusion criteria were peacetime or wartime veterans regardless of branch of service and included those for whom the traumatic brain injury was not service related. SPECT imaging was performed on this group both at rest and during a concentration task. These measures, as well as the baseline-concentration difference, were then inputted from DMN regions into separate binary logistic regression models controlling for age, gender, race, clinic site, co-morbid psychiatric diseases, TBI severity, whether or not the TBI was service related, and branch of armed service. Predicted probabilities were then inputted into a receiver operating characteristic analysis to compute sensitivity, specificity, and accuracy. Compared to PSTD, persons with TBI were older, male, and had higher rates of bipolar and major depressive disorder (p < 0.05). Baseline quantitative regions with SPECT separated PTSD from TBI in the veterans with 92 % sensitivity, 85 % specificity, and 94 % accuracy. With concentration scans, there was 85 % sensitivity, 83 % specificity and 89 % accuracy. Baseline-concentration (the difference metric between the two scans) scans were 85 % sensitivity, 80 % specificity, and 87 % accuracy. In separating TBI from PTSD/TBI visual readings of baseline scans had 85 % sensitivity, 81 % specificity, and 83 % accuracy. Concentration scans had 80 % sensitivity, 65 % specificity, and 79 % accuracy. Baseline-concentration scans had 82�

Altered Effective Connectivity of Hippocampus-Dependent Episodic Memory Network in mTBI Survivors

PubMed Central

2016-01-01

Traumatic brain injuries (TBIs) are generally recognized to affect episodic memory. However, less is known regarding how external force altered the way functionally connected brain structures of the episodic memory system interact. To address this issue, we adopted an effective connectivity based analysis, namely, multivariate Granger causality approach, to explore causal interactions within the brain network of interest. Results presented that TBI induced increased bilateral and decreased ipsilateral effective connectivity in the episodic memory network in comparison with that of normal controls. Moreover, the left anterior superior temporal gyrus (aSTG, the concept forming hub), left hippocampus (the personal experience binding hub), and left parahippocampal gyrus (the contextual association hub) were no longer network hubs in TBI survivors, who compensated for hippocampal deficits by relying more on the right hippocampus (underlying perceptual memory) and the right medial frontal gyrus (MeFG) in the anterior prefrontal cortex (PFC). We postulated that the overrecruitment of the right anterior PFC caused dysfunction of the strategic component of episodic memory, which caused deteriorating episodic memory in mTBI survivors. Our findings also suggested that the pattern of brain network changes in TBI survivors presented similar functional consequences to normal aging. PMID:28074162

Hubs defined with participation coefficient metric altered following acute mTBI

NASA Astrophysics Data System (ADS)

Wang, Xiaocui; Sun, Chuanzhu; Wang, Shan; Cao, Jieli; Xu, Hui; Gan, Shuoqiu; Chen, Zhen; Yin, Bo; Bai, Guanghui; Shao, Meihua; Gu, Chenghui; Hu, Liuxun; Ye, Limei; Li, Dandong; Yan, Zhihan; Bai, Lijun

2018-03-01

Patients with mild traumatic brain injury (mTBI) may suffer from a widespread spectrum of symptoms that arise from the damage of long-distance white matter connections in distributed brain networks. In brain networks, an increasing attention has been devoted to assessing the functional roles of regions by estimating the spatial layout of their connections among different modules, using the participation coefficient. In the present study, we aimed to investigate the role of hubs in inter-subnetwork information coordination and integration by using participation coefficients after mTBI. 74 patients after mTBI within 7 days post-injury and 51 matched healthy controls enrolled in this study. Our results presented that hubs for mTBI patients distributed in more extensive networks such as the default mode network (DMN), ventral attention network (VAN) and frontoparietal network (FPN), somatomotor network (SMN) and visual network (VN), compared with healthy controls limited to the first three. Participation coefficients for mTBI presented significantly decreased in the DMN (P=0.015) and FPN (P=0.02), while increased in the VN (P=0.035). SVM trained with participation coefficient metrics were able to identify mTBI patients from controls with 78% accuracy, providing for its diagnose potential in clinical settings. From our point of view, difference between two groups could be related with functional network reorganization in mTBI groups.

Neurotransmitter Systems in a Mild Blast Traumatic Brain Injury Model: Catecholamines and Serotonin.

PubMed

Kawa, Lizan; Arborelius, Ulf P; Yoshitake, Takashi; Kehr, Jan; Hökfelt, Tomas; Risling, Mårten; Agoston, Denes

2015-08-15

Exposure to improvised explosive devices can result in a unique form of traumatic brain injury--blast-induced traumatic brain injury (bTBI). At the mild end of the spectrum (mild bTBI [mbTBI]), there are cognitive and mood disturbances. Similar symptoms have been observed in post-traumatic stress disorder caused by exposure to extreme psychological stress without physical injury. A role of the monoaminergic system in mood regulation and stress is well established but its involvement in mbTBI is not well understood. To address this gap, we used a rodent model of mbTBI and detected a decrease in immobility behavior in the forced swim test at 1 d post-exposure, coupled with an increase in climbing behavior, but not after 14 d or later, possibly indicating a transient increase in anxiety-like behavior. Using in situ hybridization, we found elevated messenger ribonucleic acid levels of both tyrosine hydroxylase and tryptophan hydroxylase 2 in the locus coeruleus and the dorsal raphe nucleus, respectively, as early as 2 h post-exposure. High-performance liquid chromatography analysis 1 d post-exposure primarily showed elevated noradrenaline levels in several forebrain regions. Taken together, we report that exposure to mild blast results in transient changes in both anxiety-like behavior and brain region-specific molecular changes, implicating the monoaminergic system in the pathobiology of mbTBI.

Indicators of complicated mild TBI predict MMPI-2 scores after 23 years.

PubMed

Hessen, Erik; Nestvold, Knut

2009-03-01

Research suggests that post-concussive syndrome may become persistent after mild traumatic brain injury (mTBI). The aim of this study was to investigate determinants of subjective complaints, characteristic for post-concussive syndrome, 23 years after mTBI. The study was a follow-up after a prospective head injury study at a general hospital in Norway. Ninety-seven patients were assessed with the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) 23 years after sustaining primarily mTBI. A good overall outcome was found with scores close to the normative mean, average length of education and normal employment rate. However, the patients that sustained complicated mTBI showed somewhat more pathological scores, well-matched with mild post-concussive syndrome. The most important predictors of poor outcome were a combination of post-traumatic amnesia >30 minutes and EEG pathology within 24 hours after TBI. No influence of pre- and post-injury risk factors on current MMPI-2 profiles was found. The results are in line with previous research findings and support the notion of potentially differential impact of uncomplicated vs. complicated mTBI. The findings suggest that complicated mTBI may cause subtle chronic symptoms typical of post-concussive syndrome.

White matter abnormalities are associated with overall cognitive status in blast-related mTBI.

PubMed

Miller, Danielle R; Hayes, Jasmeet P; Lafleche, Ginette; Salat, David H; Verfaellie, Mieke

2017-08-01

Blast-related mild traumatic brain injury (mTBI) is a common injury of the Iraq and Afghanistan Wars. Research has suggested that blast-related mTBI is associated with chronic white matter abnormalities, which in turn are associated with impairment in neurocognitive function. However, findings are inconsistent as to which domains of cognition are affected by TBI-related white matter disruption. Recent evidence that white matter abnormalities associated with blast-related mTBI are spatially variable raises the possibility that the associated cognitive impairment is also heterogeneous. Thus, the goals of this study were to examine (1) whether mTBI-related white matter abnormalities are associated with overall cognitive status and (2) whether white matter abnormalities provide a mechanism by which mTBI influences cognition. Ninety-six Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OEF) veterans were assigned to one of three groups: no-TBI, mTBI without loss of consciousness (LOC) (mTBI-LOC), and mTBI with LOC (mTBI + LOC). Participants were given a battery of neuropsychological tests that were selected for their sensitivity to mTBI. Results showed that number of white matter abnormalities was associated with the odds of having clinically significant cognitive impairment. A mediation analysis revealed that mTBI + LOC was indirectly associated with cognitive impairment through its effect on white matter integrity. These results suggest that cognitive difficulties in blast-related mTBI can be linked to injury-induced neural changes when taking into account the variability of injury as well as the heterogeneity in cognitive deficits across individuals.

Robust training attenuates TBI-induced deficits in reference and working memory on the radial 8-arm maze

PubMed Central

Sebastian, Veronica; Diallo, Aissatou; Ling, Douglas S. F.; Serrano, Peter A.

2013-01-01

Globally, it is estimated that nearly 10 million people sustain severe brain injuries leading to hospitalization and/or death every year. Amongst survivors, traumatic brain injury (TBI) results in a wide variety of physical, emotional and cognitive deficits. The most common cognitive deficit associated with TBI is memory loss, involving impairments in spatial reference and working memory. However, the majority of research thus far has characterized the deficits associated with TBI on either reference or working memory systems separately, without investigating how they interact within a single task. Thus, we examined the effects of TBI on short-term working and long-term reference memory using the radial 8-arm maze (RAM) with a sequence of four baited and four unbaited arms. Subjects were given 10 daily trials for 6 days followed by a memory retrieval test 2 weeks after training. Multiple training trials not only provide robust training, but also test the subjects' ability to frequently update short-term memory while learning the reference rules of the task. Our results show that TBI significantly impaired short-term working memory function on previously acquired spatial information but has little effect on long-term reference memory. Additionally, TBI significantly increased working memory errors during acquisition and reference memory errors during retention testing 2 weeks later. With a longer recovery period after TBI, the robust RAM training mitigated the reference memory deficit in retention but not the short-term working memory deficit during acquisition. These results identify the resiliency and vulnerabilities of short-term working and long-term reference memory to TBI in the context of robust training. The data highlight the role of cognitive training and other behavioral remediation strategies implicated in attenuating deficits associated with TBI. PMID:23653600

Frontoparietal priority maps as biomarkers for mTBI

DTIC Science & Technology

2016-10-01

spatial attention and eye movement deficits associated with mTBI result from disruption of the gray matter and/or the white matter in cortical...The hypothesis being tested is that spatial attention and eye movement deficits associated with mTBI result from disruption of the gray matter and/or...select agents Nothing to report. PRODUCTS o Publications, conference papers, and presentations “Visual Attention and Eye Movement Deficits in

Neurologic Functional and Quality of Life Outcomes after TBI: Clinic Attendees versus Non-Attendees

PubMed Central

Wilson, Laura D.; Bregman, Jana A.; Leath, Taylor C.; Humble, Stephen S.; Davidson, Mario A.; de Riesthal, Michael R.; Guillamondegui, Oscar D.

2015-01-01

Abstract This investigation describes the relationship between TBI patient demographics, quality of life outcome, and functional status outcome among clinic attendees and non-attendees. Of adult TBI survivors with intracranial hemorrhage, 63 attended our TBI clinic and 167 did not attend. All were telephone surveyed using the Extended-Glasgow Outcome Scale (GOSE), the Quality of Life after Brain Injury (QOLIBRI) scale, and a post-discharge therapy questionnaire. To determine risk factors for GOSE and QOLIBRI outcomes, we created multivariable regression models employing covariates of age, injury characteristics, clinic attendance, insurance status, post-discharge rehabilitation, and time from injury. Compared with those with severe TBI, higher GOSE scores were identified in individuals with both mild (odds ratio [OR]=2.0; 95% confidence interval [CI]: 1.1–3.6) and moderate (OR=4.7; 95% CI: 1.6–14.1) TBIs. In addition, survivors with private insurance had higher GOSE scores, compared with those with public insurance (OR=2.0; 95% CI: 1.1–3.6), workers' compensation (OR=8.4; 95% CI: 2.6–26.9), and no insurance (OR=3.1; 95% CI: 1.6–6.2). Compared with those with severe TBI, QOLIBRI scores were 11.7 points (95% CI: 3.7–19.7) higher in survivors with mild TBI and 17.3 points (95% CI: 3.2–31.5) higher in survivors with moderate TBI. In addition, survivors who received post-discharge rehabilitation had higher QOLIBRI scores by 11.4 points (95% CI: 3.7–19.1) than those who did not. Survivors with private insurance had QOLIBRI scores that were 25.5 points higher (95% CI: 11.3–39.7) than those with workers' compensation and 16.8 points higher (95% CI: 7.4–26.2) than those without insurance. Because neurologic injury severity, insurance status, and receipt of rehabilitation or therapy are independent risk factors for functional and quality of life outcomes, future directions will include improving earlier access to post-TBI rehabilitation, social work

Sleep Disturbances, TBI and PTSD: Implications for Treatment and Recovery

PubMed Central

Gilbert, Karina Stavitsky; Kark, Sarah M.; Gehrman, Philip; Bogdanova, Yelena

2015-01-01

Post-Traumatic Stress Disorder (PTSD), traumatic brain injury (TBI), and sleep problems significantly affect recovery and functional status in military personnel and Veterans returning from combat. Despite recent attention, sleep is understudied in the Veteran population. Few treatments and rehabilitation protocols target sleep, although poor sleep remains at clinical levels and continues to adversely impact functioning even after the resolution of PTSD or mild TBI symptoms. Recent developments in non-pharmacologic sleep treatments have proven efficacious as stand-alone interventions and have potential to improve treatment outcomes by augmenting traditional behavioral and cognitive therapies. This review discusses the extensive scope of work in the area of sleep as it relates to TBI and PTSD, including pathophysiology and neurobiology of sleep; existing and emerging treatment options; as well as methodological issues in sleep measurements for TBI and PTSD. Understanding sleep problems and their role in the development and maintenance of PTSD and TBI symptoms may lead to improvement in overall treatment outcomes while offering a non-stigmatizing entry in mental health services and make current treatments more comprehensive by helping to address a broader spectrum of difficulties. PMID:26164549

Linac-based total body irradiation (TBI) with volumetric modulated arc therapy (VMAT)

NASA Astrophysics Data System (ADS)

Tas, B.; Durmus, I. F.; Okumus, A.; Uzel, O. E.

2017-02-01

To evaluate dose distribution of Volumetric modulated arc therapy (VMAT) planning tecnique using Versa HD® lineer accelerator to deliver Total Body Irradiation (TBI) on the coach. Eight TBI patient's Treatment Planning System (TPS) were performed with dual arc VMAT for each patient. The VMAT-TBI consisted of three isocentres and three dual overlapping arcs. The prescribed dose was 12 Gy. Mean dose to lung and kidney were restricted less than 10 Gy and max. dose to lens were restricted less than 6 Gy. The plans were verified using 2D array and ion chamber. The comparison between calculation and measurement were made by γ-index analysis and absolute dose. An average total delivery time was determined 923±34 seconds and an average MU was determined 2614±228 MUs for dual arc VMAT. Mean dose to lungs was 9.7±0.2 Gy, mean dose to kidneys was 8.8±0.3 Gy, max. dose to lens was 5.5±0.3 Gy and max. dose was 14.6±0.3 Gy, HI of PTV was 1.13±0.2, mean dose to PTV was 12.6±1.5 Gy and mean γ-index pass rate was %97.1±1.9. The results show that the tecnique for TBI using VMAT on the treatment coach is feasible.

Comparative Effectiveness of Family Problem-Solving Therapy (F-PST) for Adolescent TBI

ClinicalTrials.gov

2018-01-25

Tbi; Intracranial Edema; Brain Edema; Craniocerebral Trauma; Head Injury; Brain Hemorrhage, Traumatic; Subdural Hematoma; Brain Concussion; Head Injuries, Closed; Epidural Hematoma; Cortical Contusion; Wounds and Injuries; Disorders of Environmental Origin; Trauma, Nervous System; Brain Injuries

TBI Symptoms, Diagnosis, Treatment, Prevention

MedlinePlus

... Bar Home Current Issue Past Issues Cover Story: Traumatic Brain Injury TBI Symptoms, Diagnosis, Treatment, Prevention Past Issues / Fall ... very lucky in my ongoing recovery from the traumatic brain injury I suffered in Iraq." —Bob Woodruff Treatment Immediate ...

How Do Health Care Providers Diagnose Traumatic Brain Injury (TBI)?

MedlinePlus

... correlation between initial GCS score and the person's short- or long-term recovery or abilities. 2 Measurements for Level of TBI Health care providers sometimes rank the person's level of consciousness, memory loss, and GCS score. A TBI is considered ...

Using Naturalistic Methods to Examine Real-World Driving Behavior in Individuals With TBI Upon Return to Driving: A Pilot Study.

PubMed

Hua, Phuong; Charlton, Judith L; Ponsford, Jennie L; Gooden, James R; Ross, Pamela E; Bédard, Michel; Marshall, Shawn; Gagnon, Sylvain; Stolwyk, Renerus J

2018-05-31

To characterize the real-world driving habits of individuals with traumatic brain injury (TBI) using naturalistic methods and to demonstrate the feasibility of such methods in exploring return to driving after TBI. After passing an on-road driving assessment, 8 participants with TBI and 23 matched controls had an in-vehicle device installed to record information regarding their driving patterns (distance, duration, and start/end times) for 90 days. The overall number of trips, distance and duration or percentage of trips during peak hour, above 15 km from home or on freeways/highways did not differ between groups. However, the TBI group drove significantly less at night, and more during the daytime, than controls. Exploratory analyses using geographic information system (GIS) also demonstrated significant within-group heterogeneity for the TBI group in terms of location of travel. The TBI and control groups were largely comparable in terms of driving exposure, except for when they drove, which may indicate small group differences in driving self-regulatory practices. However, the GIS evidence suggests driving patterns within the TBI group were heterogeneous. These findings provide evidence for the feasibility of employing noninvasive in-car recording devices to explore real-world driving behavior post-TBI.

Post-TBI cognitive performance is moderated by variation within ANKK1 and DRD2 genes

PubMed Central

Failla, Michelle D.; Myrga, John M.; Ricker, Joseph H.; Dixon, C. Edward; Conley, Yvette P.; Wagner, Amy K.

2014-01-01

Objective As dopamine neurotransmission impacts cognition, we hypothesized variants in the linked dopamine D2 receptor (DRD2) and ankyrin repeat and kinase domain (ANKK1) genes might account for some individual variability in cognitive recovery post-TBI. Participants Prospective cohort of 108 survivors of severe TBI, recruited consecutively from a level 1 trauma center. Design We examined relationships between DRD2 genetic variation and functional recovery at 6 and 12 months post-TBI. Main Measures Cognitive performance was evaluated using 8 neuropsychological tests targeting different cognitive domains. An overall cognitive composite was developed based on normative data. We also assessed functional cognition, depression status, and global outcome. Subjects were genotyped for 6 DRD2 tagging single nucleotide polymorphisms and Taq1A within ANKK1. Results ANKK1 Taq1A heterozygotes performed better than homozygotes across several cognitive domains at both time-points post-injury. When adjusting for age, GCS, and education, the Taq1A (ANKK1) and rs6279 (DRD2) variants were associated with overall composite scores at 6 months post-TBI (p=0.0468, 0.0430, respectively). At 12 months, only Taq1A remained a significant genetic predictor of cognition (p=0.0128). Following multiple comparisons correction, there were no significant associations between examined genetic variants and functional cognition, depression status, and global outcome. Conclusion These data suggest genetic variation within DRD2 influences cognitive recovery post-TBI. Understanding genetic influences on dopaminergic systems post-TBI may impact current treatment paradigms. PMID:25931179

Exendin-4, a glucagon-like peptide-1 receptor agonist prevents mTBI-induced changes in hippocampus gene expression and memory deficits in mice

PubMed Central

Tweedie, D.; Rachmany, L.; Rubovitch, V.; Lehrmann, E.; Zhang, Y.; Becker, K.G.; Perez, E.; Miller, J.; Hoffer, B.J.; Greig, N.H.; Pick, C.G.

2012-01-01

Traumatic brain injury (TBI) is a global problem reaching near epidemic numbers that manifests clinically with cognitive problems that decades later may result in dementias like Alzheimer’s disease (AD). Presently, little can be done to prevent ensuing neurological dysfunctions by pharmacological means. Recently, it has become apparent that several CNS diseases share common terminal features of neuronal cell death. The effects of exendin-4 (Ex-4), a neuroprotective agent delivered via a subcutaneous micro-osmotic pump, were examined in the setting of mild TBI (mTBI). Utilizing a model of mTBI, where cognitive disturbances occur over time, animals were subjected to four treatments: sham; Ex-4; mTBI and Ex-4/mTBI. mTBI mice displayed deficits in novel object recognition, while Ex-4/mTBI mice performed similar to sham. Hippocampal gene expression, assessed by gene array methods, showed significant differences with little overlap in co-regulated genes between groups. Importantly, changes in gene expression induced by mTBI, including genes associated with AD were largely prevented by Ex-4. These data suggest a strong beneficial action of Ex-4 in managing secondary events induced by a traumatic brain injury. PMID:23059457

Preliminary associations between brain derived neurotrophic factor, memory impairment, functional cognition, and depressive symptoms following severe TBI

PubMed Central

Failla, Michelle D.; Juengst, Shannon B.; Arenth, Patricia; Wagner, Amy K.

2015-01-01

Background Traumatic brain injury (TBI) often leads to mood and cognitive complications, impacting functional recovery. Understanding neurobiological alterations common in post-TBI depression (PTD) and cognition may identify novel biomarkers for TBI complications. Brain-derived neurotrophic factor (BDNF) is a likely target based on evidence of reduced BDNF signaling in experimental TBI and depression models and its role in learning and memory. Objective Evaluate BDNF as a biomarker for PTD, cognitive impairment, and functional cognition in a prospective cohort with severe TBI. Methods Participants with TBI (n=113) were evaluated for PTD (Patient Health Questionnaire-9), cognitive impairment (cognitive composite score) and functional cognition (Functional Independence Measure–Cognition, FIM-Cog). BDNF levels were measured in cerebrospinal fluid (CSF) and serum 0–6 days post-injury and in serum at 6 and 12 months post-injury. Results Serum BDNF was reduced after TBI versus controls at all time-points. Acute serum BDNF positively correlated with Memory composites (6 months: r=0.43, p=0.019, n=30; 12 months: r=0.53, p=0.005, n=26) and FIM-Memory scores (6 months: r=0.35, p=0.019, n=45; 12 months: r=0.38, p=0.018, n=38). Acute serum BDNF negatively correlated with 12 month PHQ-9 scores (r=−0.38, p=0.044, n=29). At 12 months, chronic serum BDNF tended to be lower in participants with PTD (p=0.07) and correlated with PHQ-9 scores (r=−0.41, p=0.019, n=32). Conclusions Acute BDNF associations with memory recovery may implicate hippocampal damage/degeneration. Comparatively, BDNF associations with PTD status were not as strong as associations with PTD severity. Further investigation may delineate longitudinal BDNF patterns, and BDNF responsive treatments, reflecting mood and cognitive recovery following TBI. PMID:26276123

Ubiquinol treatment for TBI in male rats: Effects on mitochondrial integrity, injury severity, and neurometabolism.

PubMed

Pierce, Janet D; Gupte, Raeesa; Thimmesch, Amanda; Shen, Qiuhua; Hiebert, John B; Brooks, William M; Clancy, Richard L; Diaz, Francisco J; Harris, Janna L

2018-06-01

Following traumatic brain injury (TBI), there is significant secondary damage to cerebral tissue from increased free radicals and impaired mitochondrial function. This imbalance between reactive oxygen species (ROS) production and the effectiveness of cellular antioxidant defenses is termed oxidative stress. Often there are insufficient antioxidants to scavenge ROS, leading to alterations in cerebral structure and function. Attenuating oxidative stress following a TBI by administering an antioxidant may decrease secondary brain injury, and currently many drugs and supplements are being investigated. We explored an over-the-counter supplement called ubiquinol (reduced form of coenzyme Q10), a potent antioxidant naturally produced in brain mitochondria. We administered intra-arterial ubiquinol to rats to determine if it would reduce mitochondrial damage, apoptosis, and severity of a contusive TBI. Adult male F344 rats were randomly assigned to one of three groups: (1) Saline-TBI, (2) ubiquinol 30 minutes before TBI (UB-PreTBI), or (3) ubiquinol 30 minutes after TBI (UB-PostTBI). We found when ubiquinol was administered before or after TBI, rats had an acute reduction in brain mitochondrial damage, apoptosis, and two serum biomarkers of TBI severity, glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1). However, in vivo neurometabolic assessment with proton magnetic resonance spectroscopy did not show attenuated injury-induced changes. These findings are the first to show that ubiquinol preserves mitochondria and reduces cellular injury severity after TBI, and support further study of ubiquinol as a promising adjunct therapy for TBI. © 2018 Wiley Periodicals, Inc.

Postconcussive symptoms (PCS) following combat-related traumatic brain injury (TBI) in Veterans with posttraumatic stress disorder (PTSD): Influence of TBI, PTSD, and depression on symptoms measured by the Neurobehavioral Symptom Inventory (NSI).

PubMed

Porter, Katherine E; Stein, Murray B; Martis, Brian; Avallone, Kimberly M; McSweeney, Lauren B; Smith, Erin R; Simon, Naomi M; Gargan, Sean; Liberzon, Israel; Hoge, Charles W; Rauch, Sheila A M

2018-07-01

Mild traumatic brain injury (mTBI) is commonly reported in recent combat Veterans. While the majority resolve, some Veterans develop postconcussive symptoms (PCS). Previous research suggests these symptoms are not specific to head injury and are often associated with psychiatric symptoms. The current study examines the relative contributions of posttraumatic stress, depressive symptoms, and TBI on postconcussive symptoms, and explores whether the relationship remains after controlling for symptom overlap. Two hundred eighteen combat Veterans from Operation Iraqi Freedom (OIF), Operation Enduring Freedom (OEF), and Operation New Dawn (OND) provided the data for this study as part of a baseline evaluation for inclusion into larger treatment study for posttraumatic stress disorder (PTSD). Participants completed the Brief Traumatic Brain Injury Screen (BTBIS), Neurobehavioral Symptom Inventory (NSI), PTSD Checklist-Stressor Version (PCL-S), Beck Depression Inventory-II (BDI-II). Significant differences in NSI total score between individuals with and without history of TBI were not found. A series of regression analyses demonstrated that Depression and PTSD were significant predictors of NSI score even after removal of NSI symptoms that overlap with PTSD or depression. TBI status was also a significant predictor of PCS in most models, but its relative contribution was much smaller than that of depression and PTSD. Within PTSD symptoms, hyperarousal cluster was a significant predictor of NSI scores. Findings demonstrate that depression and PTSD are related to PCS beyond similarities in construct. Further, within a primarily PTSD treatment-seeking population, these psychiatric symptoms appear to be a stronger contributor than TBI. Copyright © 2018. Published by Elsevier Ltd.

TBI server: a web server for predicting ion effects in RNA folding.

PubMed

Zhu, Yuhong; He, Zhaojian; Chen, Shi-Jie

2015-01-01

Metal ions play a critical role in the stabilization of RNA structures. Therefore, accurate prediction of the ion effects in RNA folding can have a far-reaching impact on our understanding of RNA structure and function. Multivalent ions, especially Mg²⁺, are essential for RNA tertiary structure formation. These ions can possibly become strongly correlated in the close vicinity of RNA surface. Most of the currently available software packages, which have widespread success in predicting ion effects in biomolecular systems, however, do not explicitly account for the ion correlation effect. Therefore, it is important to develop a software package/web server for the prediction of ion electrostatics in RNA folding by including ion correlation effects. The TBI web server http://rna.physics.missouri.edu/tbi_index.html provides predictions for the total electrostatic free energy, the different free energy components, and the mean number and the most probable distributions of the bound ions. A novel feature of the TBI server is its ability to account for ion correlation and ion distribution fluctuation effects. By accounting for the ion correlation and fluctuation effects, the TBI server is a unique online tool for computing ion-mediated electrostatic properties for given RNA structures. The results can provide important data for in-depth analysis for ion effects in RNA folding including the ion-dependence of folding stability, ion uptake in the folding process, and the interplay between the different energetic components.

Radionuclide imaging of myocardial infarction using Tc-99m TBI

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holman, B.L.; Campbell, S.; Kirshenbaum, J.M.

The cationic complex Tc-99m t-butylisonitrile (TBI) concentrates in the myocardial tissue of several animal species. Its myocardial distribution is proportional to blood flow both in zones of ischemia and in normal myocardium at rest. Planar, tomographic, and gated myocardial images have been obtained using Tc-99m TBI in the human. The authors investigated the potential application of Tc-99m TBI imaging to detect and localize myocardial infarction. Four subjects without clinical evidence of cardiovascular disease and five patients with ECG evidence of previous myocardial infarction were studied. Tc-99m TBI (10mCi) was injected intravenously with the patient in a resting state with planarmore » imaging in the anterior, 30 and 70 degree LAO projections beginning one hr after injection. The distribution of the tracer was homogeneous throughout the left ventricular wall in the normal subjects. Regional perfusion defects were present in 4/5 of the patients with myocardial infarction. Location of the defects corresponded to the location of the infarct using ECG criteria (2 inferoposterior and 2 anterior). The patient in whom the Tc-99m TBI image appeared normal had sustained a subendocardial myocardial infarct which could not be localized by ECG; the other 4 pts had transmural infarcts. Anterior and 30 degree LAO images were of excellent quality in all cases; there was overlap of the liver on the inferior wall of the left ventricle on the 70 degree LAO views. The authors conclude that accurate perfusion imaging may be possible using Tc-99m TBI in patients with transmural myocardial infarction.« less

Traumatic brain injury among female offenders in a prison population: results of the FleuryTBI study.

PubMed

Durand, Eric; Watier, Laurence; Lécu, Anne; Fix, Michel; Weiss, Jean-Jacques; Chevignard, Mathilde; Pradat-Diehl, Pascale

2017-01-01

The study was designed to estimate the prevalence of traumatic brain injury (TBI) in a French prison population of female offenders, study the variables known to be associated with TBI, and compare our results with those obtained among male offenders as described in a previous paper. All female offenders (adults and juveniles) consecutively admitted to Fleury-Mérogis prison over a 3-month period were included in the study. During the admission procedure, female offenders were interviewed by healthcare staff using a self-reported questionnaire. In all, 100 female offenders were included. The rate of self-reported TBI was high, with a prevalence of 21%. The first cause of TBI was violence related (35%) and a majority of female offenders with a history of TBI reported having sustained more than one TBI. When compared with those who did not report a TBI, epilepsy and use of alcohol were higher among female offenders with a history of TBI. Perceived health was significantly worse for women who reported a TBI. This study findings provide additional evidence that TBI among offender populations is serious and that specific actions need to be developed and implemented in correctional settings such as screening for TBI upon arrival.

Disconnection and hyper-connectivity underlie reorganization after TBI: A rodent functional connectomic analysis

PubMed Central

Harris, N.G.; Verley, D.R.; Gutman, B.A.; Thompson, P.M.; Yeh, H.J.; Brown, J.A.

2016-01-01

While past neuroimaging methods have contributed greatly to our understanding of brain function after traumatic brain injury (TBI), resting state functional MRI (rsfMRI) connectivity methods have more recently provided a far more unbiased approach with which to monitor brain circuitry compared to task-based approaches. However, current knowledge on the physiologic underpinnings of the correlated blood oxygen level dependent signal, and how changes in functional connectivity relate to reorganizational processes that occur following injury is limited. The degree and extent of this relationship remain to be determined in order that rsfMRI methods can be fully adapted for determining the optimal timing and type of rehabilitative interventions that can be used post-TBI to achieve the best outcome. Very few rsfMRI studies exist after experimental TBI and therefore we chose to acquire rsfMRI data before and at 7, 14 and 28 days after experimental TBI using a well-known, clinically-relevant, unilateral controlled cortical impact injury (CCI) adult rat model of TBI. This model was chosen since it has widespread axonal injury, a well-defined time-course of reorganization including spine, dendrite, axonal and cortical map changes, as well as spontaneous recovery of sensorimotor function by 28 d post-injury from which to interpret alterations in functional connectivity. Data were co-registered to a parcellated rat template to generate adjacency matrices for network analysis by graph theory. Making no assumptions about direction of change, we used two-tailed statistical analysis over multiple brain regions in a data-driven approach to access global and regional changes in network topology in order to assess brain connectivity in an unbiased way. Our main hypothesis was that deficits in functional connectivity would become apparent in regions known to be structurally altered or deficient in axonal connectivity in this model. The data show the loss of functional connectivity

Integrated Eye Tracking and Neural Monitoring for Enhanced Assessment of Mild TBI

DTIC Science & Technology

2017-06-01

report. 10 Supporting Data None. Integrated Eye Tracking and Neural Monitoring for Enhanced Assessment of Mild TBI Psychological Health...Award Number: W81XWH-13-1-0095 TITLE: Integrated Eye Tracking and Neural Monitoring for Enhanced Assessment of Mild TBI PRINCIPAL INVESTIGATOR...COVERED 08 MAR 2016 – 07 MAR 2017 4. TITLE AND SUBTITLE Integrated Eye Tracking and Neural Monitoring for Enhanced Assessment of Mild TBI 5a

Pupillometry and Saccades as Objective mTBI Biomark

DTIC Science & Technology

2017-06-01

pupillometers, King-Devick (KD) test and near point of convergence (NPC) rule, respectively. Hundred acute mTBI (≤72 hrs post injury) and 100 age-matched... test  and NPC are also significantly effected in mTBI group.  Task 3: Data Analysis and Report Writing mTBI Control 6/28/2017 1 Medical Research and...U.S. Army Aeromedical Research Laboratory Fort Rucker, Alabama UNCLASSIFIED King-Devick Test 10 *P < 0.0001 Medical Research and Materiel Command U.S

Enhanced Cognitive Rehabilitation to Treat Comorbid TBI and PTSD

DTIC Science & Technology

2017-12-01

S) Amy Jak 5d. PROJECT NUMBER 5e. TASK NUMBER E-Mail: ajak@ucsd.edu 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES...symptoms resulting from mild to moderate TBI. These practice standards have been organized into a manualized treatment, Cognitive Symptom Management ...Processing Therapy; SMART-CPT=Cognitive Symptom Management and Rehabilitation Therapy combined with CPT; TBI=traumatic brain injury; PTSD=posttraumatic

Electropalatographic (EPG) assessment of tongue-to-palate contacts in dysarthric speakers following TBI.

PubMed

Kuruvilla, Mili S; Murdoch, Bruce E; Goozee, Justine V

2008-09-01

The aim of the investigation was to compare EPG-derived spatial and timing measures between a group of 11 dysarthric individuals post-severe TBI and 10 age- and sex-matched neurologically non-impaired individuals. Participants of the TBI group were diagnosed with dysarthria ranging from mild-to-moderate-severe dysarthria. Each participant from the TBI and comparison group was fitted with a custom-made artificial acrylic palate that recorded lingual palatal contact during target consonant production in sentence- and syllable-repetition tasks at a habitual rate and loudness level. Analysis of temporal parameters between the comparison and TBI groups revealed prolonged durations of the various phases of consonant production, which were attributed to articulatory slowness, impaired speech motor control, impaired accuracy, and impaired coordination of articulatory movements in the dysarthric speakers post-TBI. For the spatial measurements, quantitative analysis, as well as visual inspection of the tongue-to-palate contact diagrams, indicated spatial aberrations in dysarthric speech post-TBI. Both the spatial and temporal aberrations may have at least partially caused the perceptual judgement of articulatory impairments in the dysarthric speakers.

Examining the Efficacy of the Modified Story Memory Technique (mSMT) in Persons With TBI Using Functional Magnetic Resonance Imaging (fMRI): The TBI-MEM Trial.

PubMed

Chiaravalloti, Nancy D; Dobryakova, Ekaterina; Wylie, Glenn R; DeLuca, John

2015-01-01

New learning and memory deficits are common following traumatic brain injury (TBI). Yet few studies have examined the efficacy of memory retraining in TBI through the most methodologically vigorous randomized clinical trial. Our previous research has demonstrated that the modified Story Memory Technique (mSMT) significantly improves new learning and memory in multiple sclerosis. The present double-blind, placebo-controlled, randomized clinical trial examined changes in cerebral activation on functional magnetic resonance imaging following mSMT treatment in persons with TBI. Eighteen individuals with TBI were randomly assigned to treatment (n = 9) or placebo (n = 9) groups. Baseline and follow-up functional magnetic resonance imaging was collected during a list-learning task. Significant differences in cerebral activation from before to after treatment were noted in regions belonging to the default mode network and executive control network in the treatment group only. Results are interpreted in light of these networks. Activation differences between the groups likely reflect increased use of strategies taught during treatment. This study demonstrates a significant change in cerebral activation resulting from the mSMT in a TBI sample. Findings are consistent with previous work in multiple sclerosis. Behavioral interventions can show significant changes in the brain, validating clinical utility.

Sleep quality affects cognitive functioning in returning combat veterans beyond combat exposure, PTSD, and mild TBI history.

PubMed

Martindale, Sarah L; Morissette, Sandra B; Rowland, Jared A; Dolan, Sara L

2017-01-01

The purpose of this study was to determine how sleep quality affects cognitive functioning in returning combat veterans after accounting for effects of combat exposure, posttraumatic stress disorder (PTSD), and mild traumatic brain injury (mTBI) history. This was a cross-sectional assessment study evaluating combat exposure, PTSD, mTBI history, sleep quality, and neuropsychological functioning. One hundred and nine eligible male Iraq/Afghanistan combat veterans completed an assessment consisting of a structured clinical interview, neuropsychological battery, and self-report measures. Using partial least squares structural equation modeling, combat experiences and mTBI history were not directly associated with sleep quality. PTSD was directly associated with sleep quality, which contributed to deficits in neuropsychological functioning independently of and in addition to combat experiences, PTSD, and mTBI history. Combat experiences and PTSD were differentially associated with motor speed. Sleep affected cognitive function independently of combat experiences, PTSD, and mTBI history. Sleep quality also contributed to cognitive deficits beyond effects of PTSD. An evaluation of sleep quality may be a useful point of clinical intervention in combat veterans with cognitive complaints. Improving sleep quality could alleviate cognitive complaints, improving veterans' ability to engage in treatment. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

A simplified technique for delivering total body irradiation (TBI) with improved dose homogeneity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yao Rui; Bernard, Damian; Turian, Julius

2012-04-15

Purpose: Total body irradiation (TBI) with megavoltage photon beams has been accepted as an important component of management for a number of hematologic malignancies, generally as part of bone marrow conditioning regimens. The purpose of this paper is to present and discuss the authors' TBI technique, which both simplifies the treatment process and improves the treatment quality. Methods: An AP/PA TBI treatment technique to produce uniform dose distributions using sequential collimator reductions during each fraction was implemented, and a sample calculation worksheet is presented. Using this methodology, the dosimetric characteristics of both 6 and 18 MV photon beams, including lungmore » dose under cerrobend blocks was investigated. A method of estimating midplane lung doses based on measured entrance and exit doses was proposed, and the estimated results were compared with measurements. Results: Whole body midplane dose uniformity of {+-}10% was achieved with no more than two collimator-based beam modulations. The proposed model predicted midplane lung doses 5% to 10% higher than the measured doses for 6 and 18 MV beams. The estimated total midplane doses were within {+-}5% of the prescribed midplane dose on average except for the lungs where the doses were 6% to 10% lower than the prescribed dose on average. Conclusions: The proposed TBI technique can achieve dose uniformity within {+-}10%. This technique is easy to implement and does not require complicated dosimetry and/or compensators.« less

Opioid Abuse after TBI

DTIC Science & Technology

2014-07-01

2014 2. REPORT TYPE Annual 3. DATES COVERED 1 July 2013 - 30 June 2014 4. TITLE AND SUBTITLE "Opioid Abuse after TBI" 5a. CONTRACT NUMBER 5b...17beta‐estradiol confers protection following  traumatic brain injury in the rat and involves activation of G Protein‐coupled estrogen receptor 1 ( GPER

When Injury Clouds Understanding of Others: Theory of Mind after Mild TBI in Preschool Children.

PubMed

Bellerose, Jenny; Bernier, Annie; Beaudoin, Cindy; Gravel, Jocelyn; Beauchamp, Miriam H

2015-08-01

There is evidence to suggest that social skills, such as the ability to understand the perspective of others (theory of mind), may be affected by childhood traumatic brain injuries; however, studies to date have only considered moderate and severe traumatic brain injury (TBI). This study aimed to assess theory of mind after early, mild TBI (mTBI). Fifty-one children who sustained mTBI between 18 and 60 months were evaluated 6 months post-injury on emotion and desires reasoning and false-belief understanding tasks. Their results were compared to that of 50 typically developing children. The two groups did not differ on baseline characteristics, except for pre- and post-injury externalizing behavior. The mTBI group obtained poorer scores relative to controls on both the emotion and desires task and the false-belief understanding task, even after controlling for pre-injury externalizing behavior. No correlations were found between TBI injury characteristics and theory of mind. This is the first evidence that mTBI in preschool children is associated with theory of mind difficulties. Reduced perspective taking abilities could be linked with the social impairments that have been shown to arise following TBI.

Adolescent TBI-induced hypopituitarism causes sexual dysfunction in adult male rats.

PubMed

Greco, Tiffany; Hovda, David A; Prins, Mayumi L

2015-02-01

Adolescents are at greatest risk for traumatic brain injury (TBI) and repeat TBI (RTBI). TBI-induced hypopituitarism has been documented in both adults and juveniles and despite the necessity of pituitary function for normal physical and brain development, it is still unrecognized and untreated in adolescents following TBI. TBI induced hormonal dysfunction during a critical developmental window has the potential to cause long-term cognitive and behavioral deficits and the topic currently remains unaddressed. The purpose of this study was to determine if four mild TBIs delivered to adolescent male rats disrupts testosterone production and adult behavioral outcomes. Plasma testosterone was quantified from 72 hrs preinjury to 3 months postinjury and pubertal onset, reproductive organ growth, erectile function and reproductive behaviors were assessed at 1 and 2 months postinjury. RTBI resulted in both acute and chronic decreases in testosterone production and delayed onset of puberty. Significant deficits were observed in reproductive organ growth, erectile function and reproductive behaviors in adult rats at both 1 and 2 months postinjury. These data suggest adolescent RTBI-induced hypopituitarism underlies abnormal behavioral changes observed during adulthood. The impact of undiagnosed hypopituitarism following RTBI in adolescence has significance not only for growth and puberty, but also for brain development and neurobehavioral function as adults. © 2014 Wiley Periodicals, Inc.

A study on the mechanism by which MDMA protects against dopaminergic dysfunction after minimal traumatic brain injury (mTBI) in mice.

PubMed

Edut, S; Rubovitch, V; Rehavi, M; Schreiber, S; Pick, C G

2014-12-01

Driving under methylenedioxymethamphetamine (MDMA) influence increases the risk of being involved in a car accident, which in turn can lead to traumatic brain injury. The behavioral deficits after traumatic brain injury (TBI) are closely connected to dopamine pathway dysregulation. We have previously demonstrated in mice that low MDMA doses prior to mTBI can lead to better performances in cognitive tests. The purpose of this study was to assess in mice the changes in the dopamine system that occurs after both MDMA and minimal traumatic brain injury (mTBI). Experimental mTBI was induced using a concussive head trauma device. One hour before injury, animals were subjected to MDMA. Administration of MDMA before injury normalized the alterations in tyrosine hydroxylase (TH) levels that were observed in mTBI mice. This normalization was also able to lower the elevated dopamine receptor type 2 (D2) levels observed after mTBI. Brain-derived neurotrophic factor (BDNF) levels did not change following injury alone, but in mice subjected to MDMA and mTBI, significant elevations were observed. In the behavioral tests, haloperidol reversed the neuroprotection seen when MDMA was administered prior to injury. Altered catecholamine synthesis and high D2 receptor levels contribute to cognitive dysfunction, and strategies to normalize TH signaling and D2 levels may provide relief for the deficits observed after injury. Pretreatment with MDMA kept TH and D2 receptor at normal levels, allowing regular dopamine system activity. While the beneficial effect we observe was due to a dangerous recreational drug, understanding the alterations in dopamine and the mechanism of dysfunction at a cellular level can lead to legal therapies and potential candidates for clinical use.

Disconnection and hyper-connectivity underlie reorganization after TBI: A rodent functional connectomic analysis.

PubMed

Harris, N G; Verley, D R; Gutman, B A; Thompson, P M; Yeh, H J; Brown, J A

2016-03-01

While past neuroimaging methods have contributed greatly to our understanding of brain function after traumatic brain injury (TBI), resting state functional MRI (rsfMRI) connectivity methods have more recently provided a far more unbiased approach with which to monitor brain circuitry compared to task-based approaches. However, current knowledge on the physiologic underpinnings of the correlated blood oxygen level dependent signal, and how changes in functional connectivity relate to reorganizational processes that occur following injury is limited. The degree and extent of this relationship remain to be determined in order that rsfMRI methods can be fully adapted for determining the optimal timing and type of rehabilitative interventions that can be used post-TBI to achieve the best outcome. Very few rsfMRI studies exist after experimental TBI and therefore we chose to acquire rsfMRI data before and at 7, 14 and 28 days after experimental TBI using a well-known, clinically-relevant, unilateral controlled cortical impact injury (CCI) adult rat model of TBI. This model was chosen since it has widespread axonal injury, a well-defined time-course of reorganization including spine, dendrite, axonal and cortical map changes, as well as spontaneous recovery of sensorimotor function by 28 d post-injury from which to interpret alterations in functional connectivity. Data were co-registered to a parcellated rat template to generate adjacency matrices for network analysis by graph theory. Making no assumptions about direction of change, we used two-tailed statistical analysis over multiple brain regions in a data-driven approach to access global and regional changes in network topology in order to assess brain connectivity in an unbiased way. Our main hypothesis was that deficits in functional connectivity would become apparent in regions known to be structurally altered or deficient in axonal connectivity in this model. The data show the loss of functional connectivity

The Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI): II. Reliability and Convergent Validity

PubMed Central

Wilde, Elisabeth A.; Kelly, Tara M.; Weyand, Annie M.; Yallampalli, Ragini; Waldron, Eric J.; Pedroza, Claudia; Schnelle, Kathleen P.; Boake, Corwin; Levin, Harvey S.; Moretti, Paolo

2010-01-01

Abstract A standardized measure of neurological dysfunction specifically designed for TBI currently does not exist and the lack of assessment of this domain represents a substantial gap. To address this, the Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI) was developed for TBI outcomes research through the addition to and modification of items specifically relevant to patients with TBI, based on the National Institutes of Health Stroke Scale. In a sample of 50 participants (mean age = 33.3 years, SD = 12.9) ≤18 months (mean = 3.1, SD = 3.2) following moderate (n = 8) to severe (n = 42) TBI, internal consistency of the NOS-TBI was high (Cronbach's alpha = 0.942). Test-retest reliability also was high (ρ = 0.97, p < 0.0001), and individual item kappas between independent raters were excellent, ranging from 0.83 to 1.0. Overall inter-rater agreement between independent raters (Kendall's coefficient of concordance) for the NOS-TBI total score was excellent (W = 0.995). Convergent validity was demonstrated through significant Spearman rank-order correlations between the NOS-TBI and the concurrently administered Disability Rating Scale (ρ = 0.75, p < 0.0001), Rancho Los Amigos Scale (ρ = −0.60, p < 0.0001), Supervision Rating Scale (ρ = 0.59, p < 0.0001), and the FIM™ (ρ = −0.68, p < 0.0001). These results suggest that the NOS-TBI is a reliable and valid measure of neurological functioning in patients with moderate to severe TBI. PMID:20210595

Underbody Blast Models of TBI Caused by Hyper-Acceleration and Secondary Head Impact

DTIC Science & Technology

2017-10-01

brain injury (TBI), with most of these head injuries caused by explosive munitions such as bombs , land mines, improvised explosive devices and missiles...with most of these injuries caused by explosive munitions such as bombs , land mines, improvised explosive devices (IEDs), and missiles.1,2 Little is...Neurosurg. 2008;108: 124–131. 21. Richards EM , Fiskum G, Rosenthal RE, Hopkins I, McKenna MC. Hyperoxic reperfusion after global ischemia decreases

Fatigue - but not mTBI history, PTSD, or sleep quality - directly contributes to reduced prospective memory performance in Iraq and Afghanistan era Veterans.

PubMed

Rau, Holly K; Hendrickson, Rebecca; Roggenkamp, Hannah C; Peterson, Sarah; Parmenter, Brett; Cook, David G; Peskind, Elaine; Pagulayan, Kathleen F

2017-10-13

Memory problems that affect daily functioning are a frequent complaint among Veterans reporting a history of repetitive mild traumatic brain injury (mTBI), especially in cohorts with comorbid PTSD. Here, we test the degree to which subjective sleep impairment and daytime fatigue account for the association of PTSD and self-reported mTBI history with prospective memory. 82 Veterans with and without personal history of repeated blast-related mTBI during deployment were administered the Clinician Administered PTSD Scale (CAPS), Memory for Intentions Test (MIST), Patient Health Questionnaire-9 (PHQ-9), Neurobehavioral Symptom Inventory (NSI), and the Pittsburgh Sleep Quality Index (PSQI). Relationships between self-reported mTBI, PTSD, self-reported poor sleep and daytime fatigue, and MIST performance were modeled using partial least squares structural equation modeling (PLS-SEM). Reported daytime fatigue was strongly associated with poorer prospective memory performance. Poor subjective sleep quality was strongly and positively associated with reported daytime fatigue, but had no significant direct effect on prospective memory performance. PTSD diagnosis and self-reported mTBI history were only associated with prospective memory via their impact on subjective sleep quality and daytime fatigue. Results suggest that daytime fatigue may be a mediating factor by which both mTBI and PTSD can interfere with prospective memory. Additional attention should be given to complaints of daytime fatigue, independent of subjective sleep quality, in the clinical care of those with a self-reported history of mTBI, and/or PTSD. Further research into whether interventions that decrease daytime fatigue lead to improvement in prospective memory and subjective cognitive functioning is warranted.

Intracranial pressure and cerebral perfusion pressure monitoring in non-TBI patients: special considerations.

PubMed

Helbok, Raimund; Olson, DaiWai M; Le Roux, Peter D; Vespa, Paul

2014-12-01

The effect of intracranial pressure (ICP) and the role of ICP monitoring are best studied in traumatic brain injury (TBI). However, a variety of acute neurologic illnesses e.g., subarachnoid hemorrhage, intracerebral hemorrhage, ischemic stroke, meningitis/encephalitis, and select metabolic disorders, e.g., liver failure and malignant, brain tumors can affect ICP. The purpose of this paper is to review the literature about ICP monitoring in conditions other than TBI and to provide recommendations how the technique may be used in patient management. A PubMed search between 1980 and September 2013 identified 989 articles; 225 of which were reviewed in detail. The technique used to monitor ICP in non-TBI conditions is similar to that used in TBI; however, indications for ICP monitoring often are intertwined with the presence of obstructive hydrocephalus and hence the use of ventricular catheters is more frequent. Increased ICP can adversely affect outcome, particularly when it fails to respond to treatment. However, patients with elevated ICP can still have favorable outcomes. Although the influence of ICP-based care on outcome in non-TBI conditions appears less robust than in TBI, monitoring ICP and cerebral perfusion pressure can play a role in guiding therapy in select patients.

Blood Biomarker Profile of TBI-Associated Cognitive Impairment Among Old and Young Veterans

DTIC Science & Technology

2015-10-01

associated with TBI remains unclear. Some studies link TBI to Alzheimer disease (AD) while others suggest the TBI-associated dementia is more similar to...encephalopathy (CTE), blood biomarkers, aging, cognitive impairment (CI), Alzheimer ’s disease (AD) Accomplishments • What were the major goals of the...Yountville, CA: Months 6-18  Data collection is currently ongoing at both sites. o Enroll 80 veterans with mild Alzheimer Disease (AD) at AFRH and VHC-Y

Fractal Analysis of Brain Blood Oxygenation Level Dependent (BOLD) Signals from Children with Mild Traumatic Brain Injury (mTBI).

PubMed

Dona, Olga; Noseworthy, Michael D; DeMatteo, Carol; Connolly, John F

2017-01-01

Conventional imaging techniques are unable to detect abnormalities in the brain following mild traumatic brain injury (mTBI). Yet patients with mTBI typically show delayed response on neuropsychological evaluation. Because fractal geometry represents complexity, we explored its utility in measuring temporal fluctuations of brain resting state blood oxygen level dependent (rs-BOLD) signal. We hypothesized that there could be a detectable difference in rs-BOLD signal complexity between healthy subjects and mTBI patients based on previous studies that associated reduction in signal complexity with disease. Fifteen subjects (13.4 ± 2.3 y/o) and 56 age-matched (13.5 ± 2.34 y/o) healthy controls were scanned using a GE Discovery MR750 3T MRI and 32-channel RF-coil. Axial FSPGR-3D images were used to prescribe rs-BOLD (TE/TR = 35/2000ms), acquired over 6 minutes. Motion correction was performed and anatomical and functional images were aligned and spatially warped to the N27 standard atlas. Fractal analysis, performed on grey matter, was done by estimating the Hurst exponent using de-trended fluctuation analysis and signal summation conversion methods. Voxel-wise fractal dimension (FD) was calculated for every subject in the control group to generate mean and standard deviation maps for regional Z-score analysis. Voxel-wise validation of FD normality across controls was confirmed, and non-Gaussian voxels (3.05% over the brain) were eliminated from subsequent analysis. For each mTBI patient, regions where Z-score values were at least 2 standard deviations away from the mean (i.e. where |Z| > 2.0) were identified. In individual patients the frequently affected regions were amygdala (p = 0.02), vermis(p = 0.03), caudate head (p = 0.04), hippocampus(p = 0.03), and hypothalamus(p = 0.04), all previously reported as dysfunctional after mTBI, but based on group analysis. It is well known that the brain is best modeled as a complex system. Therefore a measure of complexity

Blood Biomarker Profile of TBI-Associated Cognitive Impairment Among Old and Young Veterans

DTIC Science & Technology

2017-10-01

define the biomarker profile of TBI-associated cognitive impairment (CI) in veterans and compare it to that of veterans with Alzheimer’s Disease (AD...controls who have not had a TBI, and that 2) TBI-associated CI will be associated with elevations in inflammatory markers compared to controls and 3) a...decrease in b-amyloid measures compared to controls but not as low as in the setting of AD. We recently completed enrollment. Data from 160 participants

Metabolic alterations in patients who develop traumatic brain injury (TBI)-induced hypopituitarism.

PubMed

Prodam, F; Gasco, V; Caputo, M; Zavattaro, M; Pagano, L; Marzullo, P; Belcastro, S; Busti, A; Perino, C; Grottoli, S; Ghigo, E; Aimaretti, G

2013-08-01

Hypopituitarism is associated with metabolic alterations but in TBI-induced hypopituitarism data are scanty. The aim of our study was to evaluate the prevalence of naïve hypertension, dyslipidemia, and altered glucose metabolism in TBI-induced hypopituitarism patients. Cross-sectional retrospective study in a tertiary care endocrinology center. 54 adult patients encountering a moderate or severe TBI were evaluated in the chronic phase (at least 12 months after injury) after-trauma. Presence of hypopituitarism, BMI, hypertension, fasting blood glucose and insulin levels, oral glucose tolerance test (if available) and a lipid profile were evaluated. The 27.8% of patients showed various degrees of hypopituitarism. In particular, 9.3% had total, 7.4% multiple and 11.1% isolated hypopituitarism. GHD was present in 22.2% of patients. BMI was similar between the two groups. Hypopituitaric patients presented a higher prevalence of dyslipidemia (p<0.01) and altered glucose metabolism (p<0.005) with respect to non hypopituitaric patients. In particular, triglycerides (p<0.05) and HOMA-IR (p<0.02) were higher in hypopituitaric TBI patients. We showed that long-lasting TBI patients who develop hypopituitarism frequently present metabolic alterations, in particular altered glucose levels, insulin resistance and hypertriglyceridemia. In view of the risk of premature cardiovascular death in hypopituitaric patients, major attention has to been paid in those who encountered a TBI, because they suffer from the same comorbidities and may present other deterioration factors due to complex pharmacological treatments and restriction in participation in life activities and healthy lifestyle. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effects of categorization training in patients with TBI during postacute rehabilitation: preliminary findings.

PubMed

Constantinidou, Fofi; Thomas, Robin D; Scharp, Victoria L; Laske, Kate M; Hammerly, Mark D; Guitonde, Suchita

2005-01-01

Previous research suggests that traumatic brain injury (TBI) interferes with the ability to extract and use attributes to describe objects. This study explored the effects of a systematic Categorization Program (CP) in participants with TBI and noninjured controls. Ten persons with moderate to severe TBI who received comprehensive postacute rehabilitation services and 13 matched noninjured controls participated in the study. All participants received CP training for 3 to 5 hours per week for 10 to 12 weeks that consisted of 8 levels and targeted concept formation, object categorization, and decision-making abilities. The Mayo-Portland Adaptability Inventory-3 (MPAI-3) and the Community Integration Questionnaire (CIQ). Two Categorization Tests (administered pretraining and posttraining) and 3 Probe Tasks (administered at specified intervals during training) assessed skills relating to categorization. Both groups showed significant improvement in categorization performance after the CP training on the 2 Categorization Tests related to the CP. They also were able to generalize and apply categorization and sorting skills in new situations (as measured by the Probe Tasks). Participants with TBI had improved functional outcome performance measured by the MPAI-3 and the CIQ. The systematic and hierarchical structure of the CP is beneficial to participants with TBI during postacute rehabilitation. This study contributes to the growing body of evidence supporting cognitive rehabilitation after moderate to severe TBI.

Investigating social functioning after early mild TBI: the quality of parent-child interactions.

PubMed

Lalonde, Gabrielle; Bernier, Annie; Beaudoin, Cindy; Gravel, Jocelyn; Beauchamp, Miriam H

2018-03-01

The young brain is particularly vulnerable to injury due to inherent physiological and developmental factors, and even mild forms of traumatic brain injury (mTBI) can sometimes result in cognitive and behavioural difficulties. Despite the high prevalence of paediatric mTBI, little is known of its impact on children's social functioning. Parent-child relationships represent the centre of young children's social environments and are therefore ideal contexts for studying the potential effects of mTBI on children's social functioning. The aim of this study was to assess the quality of parent-child interactions after mTBI using observational assessment methods and parental report. The sample included 130 children (18-60 months at recruitment) divided into three groups: children with uncomplicated mTBI (n = 47), children with orthopaedic injury (OI, n = 27), and non-injured children (NI, n = 56). The quality of parent-child interactions was assessed 6 months post-injury using the Mutually Responsive Orientation (MRO) scale, an observational measure which focuses on the dyadic nature of parent-child exchanges, and the Parental Stress Index questionnaire (Parent-Child Dysfunctional Interaction (PCDI) domain). Significant differences with medium effect sizes were found between the mTBI group and the NI group on the MRO, but not between the OI group and the other two groups. PCDI scores did not differ across groups, suggesting that observational measures may be more sensitive to changes in parent-child interactions after TBI. The current findings have implications for children's post-injury social development and highlight the importance of monitoring social outcomes even after minor head injuries. © 2016 The British Psychological Society.

Quantitative Tractography and Volumetric MRI in Blast and Blunt Force TBI: Predictors of Neurocognitive and Behavioral Outcome

DTIC Science & Technology

2014-10-01

severity, suggesting dissociable neurobiologic substrates for the cognitive and psychological sequelae following mTBI (Sorg et al., 2014). mTBI...suggest dissociable neurobiologic substrates for the cognitive and psychological sequelae following mTBI (Sorg et al., 2014). 7  mTBI patients with...Neuropsychological Society, Seattle, WA, February 2014: Cognitive and Psychiatric Dissociations between Fractional Anisotropy and Cortical Thickness

Primary Blast Injury Criteria for Animal/Human TBI Models using Field Validated Shock Tubes

DTIC Science & Technology

2017-09-01

differential pathological response, which depends on the local tissue composition, and the response is to insult depends upon the cell type. regions...Neuroinflammation A single blast induces cell-type dependent increase in NADPH oxidase isoforms We have performed characterization of the spatial variations and...uniformly distribute and affect the whole brain. However, pathophysiological outcomes (e.g., NOX changes) in response to bTBI depend on the differential

Gender differences in a sample of vocational rehabilitation clients with TBI.

PubMed

Bounds, Thomas A; Schopp, Laura; Johnstone, Brick; Unger, Clarinda; Goldman, Herb

2003-01-01

Because traumatic brain injury affects between 1.5 and 2 million individuals per year and results in long term vocational and financial difficulties, there is growing interest in determining those factors that predict successful outcomes for specific groups of individuals with TBI. An NIH consensus panel on TBI has suggested that women are one group that needs more attention, particularly given the studies indicating that men and women experience different cognitive [14], emotional [19], and vocational outcomes following TBI [5]. The current study evaluated differences in injury severity, demographics, neuropsychological abilities, and vocational and financial outcomes for 78 persons with TBI (55 male, 23 female) who received services from a state Vocational Rehabilitation Division (DVR). Despite similar injury severity, neuropsychological and demographic characteristics, more men (43.6%) received Maintenance services from MO-DVR than women (21.7%). Of note, only 4.4% of the women were successfully employed through DVR, compared to 23.6% of the men. In addition, 73.9% of the women had services terminated after being accepted by DVR but before services were initiated, compared to 56.4% of the men. The significance of these results is discussed, as are the limitations of the current project.

The impact of pediatric traumatic brain injury (TBI) on family functioning: a systematic review.

PubMed

Rashid, Marghalara; Goez, Helly R; Mabood, Neelam; Damanhoury, Samah; Yager, Jerome Y; Joyce, Anthony S; Newton, Amanda S

2014-01-01

To explore the impact moderate to severe traumatic brain injury (TBI) in a child has on family functioning. The search was conducted using 9 bibliographic databases for articles published between 1980 and 2013. Two reviewers independently screened for inclusion and assessed study quality. Two reviewers extracted study data and a third checked for completeness and accuracy. Findings are presented by three domains: injury-related burden and stress, family adaptability, and family cohesion. Nine observational studies were included. Across the studies, differences between study groups for family functioning varied, but there was a trend for more dysfunction in families whose child had a severe TBI as compared to families whose child had a moderate TBI or orthopedic injury. In three studies, injury-associated burden was persistent post-injury and was highest in families whose child had a severe TBI followed by families with a child who had a moderate TBI. One study found fathers reported more family dysfunction caused by their child's injury compared to mothers. Two studies found that mothers' adaptability depended on social support and stress levels while fathers' adaptability was independent of these factors and injury severity. Moderate to severe TBI has a significant, long-standing impact on family functioning. Factors associated with family adaptability vary by parental role.

Virtual Environment TBI Screen (VETS)

DTIC Science & Technology

2016-12-01

Knowledge of acute symptoms associated with TBI can help clinicians make important decisions regarding treatment and/or return to duty. Early...sensitive (81.8%) and specific (85.7%). To further validate the VETS protocol across a wide range of time-since-injury, i.e. acute , subacute, chronic, we...2-weeks, 6-weeks) for each group healthy (white bars), acutely concussed (grey bars), prolonged PCS (black bars). The healthy group showed no

Effect of chromatic filters on visual performance in individuals with mild traumatic brain injury (mTBI): A pilot study.

PubMed

Fimreite, Vanessa; Willeford, Kevin T; Ciuffreda, Kenneth J

2016-01-01

Spectral filters have been used clinically in patients with mild traumatic brain injury (mTBI). However, they have not been formally assessed using objective techniques in this population. Thus, the aim of the present pilot study was to determine the effect of spectral filters on reading performance and visuo-cortical responsivity in adults with mTBI. 12 adults with mTBI/concussion were tested. All reported photosensitivity and reading problems. They were compared to 12 visually-normal, asymptomatic adults. There were several test conditions: three luminance-matched control filters (gray neutral density, blue, and red), the patient-selected 'precision tint lens' that provided the most comfort and clarity of text using the Intuitive Colorimeter System, and baseline without any filters. The Visagraph was used to assess reading eye movements and reading speed objectively with each filter. In addition, both the amplitude and latency of the visual-evoked potential (VEP) were assessed with the same filters. There were few significant group differences in either the reading-related parameters or VEP latency for any of the test filter conditions. Subjective improvements were noted in most with mTBI (11/12). The majority of patients with mTBI chose a tinted filter that resulted in increased visual comfort. While significant findings based on the objective testing were found for some conditions, the subjective results suggest that precision tints should be considered as an adjunctive treatment in patients with mTBI and photosensitivity. Copyright © 2016 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.

Prevalence of traumatic brain injury and epilepsy among prisoners in France: Results of the Fleury TBI study.

PubMed

Durand, E; Watier, L; Fix, M; Weiss, J J; Chevignard, M; Pradat-Diehl, P

2016-01-01

The first aim of this study was to estimate the prevalence of TBI and epilepsy in a French prison population and to study variables known to be associated with TBI. The second aim was to compare prisoners with and without a history of TBI. All offenders (females, males and juveniles) admitted consecutively to Fleury-Mérogis prison over a period of 3 months were included in the study. During the admission procedure, offenders were interviewed by healthcare staff using a self-reported questionnaire. In all, 1221 prisoners were included. The rates of TBI and epilepsy were high, with a prevalence of 30.6% and 5.9%, respectively. Psychiatric care, anxiolytic and antidepressant treatment, use of alcohol and cannabis were all significantly higher among offenders with a history of TBI. Moreover, the number of times in custody and the total time spent in jail over the preceding 5 years were significantly higher among offenders with a history of TBI. These results provide further evidence that specific measures need to be developed such as, first of all, screening for TBI upon arrival in prison.

Can Post mTBI Neurological Soft Signs Predict Postconcussive and PTSD Symptoms : A Pilot Study

DTIC Science & Technology

2014-02-01

disorders , including post - traumatic stress disorder ( PTSD ), but they have scarcely been studied in TBI. The present study measured NSS in the...including post - traumatic stress disorder ( PTSD ), but they have scarcely been studied in TBI. The present study measured NSS in the acute aftermath of...Can Post mTBI Neurological Soft Signs Predict Postconcussive and PTSD Symptoms?: A Pilot Study 5a. CONTRACT NUMBER E-Mail:

Characterizing brain structures and remodeling after TBI based on information content, diffusion entropy.

PubMed

Fozouni, Niloufar; Chopp, Michael; Nejad-Davarani, Siamak P; Zhang, Zheng Gang; Lehman, Norman L; Gu, Steven; Ueno, Yuji; Lu, Mei; Ding, Guangliang; Li, Lian; Hu, Jiani; Bagher-Ebadian, Hassan; Hearshen, David; Jiang, Quan

2013-01-01

To overcome the limitations of conventional diffusion tensor magnetic resonance imaging resulting from the assumption of a Gaussian diffusion model for characterizing voxels containing multiple axonal orientations, Shannon's entropy was employed to evaluate white matter structure in human brain and in brain remodeling after traumatic brain injury (TBI) in a rat. Thirteen healthy subjects were investigated using a Q-ball based DTI data sampling scheme. FA and entropy values were measured in white matter bundles, white matter fiber crossing areas, different gray matter (GM) regions and cerebrospinal fluid (CSF). Axonal densities' from the same regions of interest (ROIs) were evaluated in Bielschowsky and Luxol fast blue stained autopsy (n = 30) brain sections by light microscopy. As a case demonstration, a Wistar rat subjected to TBI and treated with bone marrow stromal cells (MSC) 1 week after TBI was employed to illustrate the superior ability of entropy over FA in detecting reorganized crossing axonal bundles as confirmed by histological analysis with Bielschowsky and Luxol fast blue staining. Unlike FA, entropy was less affected by axonal orientation and more affected by axonal density. A significant agreement (r = 0.91) was detected between entropy values from in vivo human brain and histologically measured axonal density from post mortum from the same brain structures. The MSC treated TBI rat demonstrated that the entropy approach is superior to FA in detecting axonal remodeling after injury. Compared with FA, entropy detected new axonal remodeling regions with crossing axons, confirmed with immunohistological staining. Entropy measurement is more effective in distinguishing axonal remodeling after injury, when compared with FA. Entropy is also more sensitive to axonal density than axonal orientation, and thus may provide a more accurate reflection of axonal changes that occur in neurological injury and disease.

Characterizing Brain Structures and Remodeling after TBI Based on Information Content, Diffusion Entropy

PubMed Central

Fozouni, Niloufar; Chopp, Michael; Nejad-Davarani, Siamak P.; Zhang, Zheng Gang; Lehman, Norman L.; Gu, Steven; Ueno, Yuji; Lu, Mei; Ding, Guangliang; Li, Lian; Hu, Jiani; Bagher-Ebadian, Hassan; Hearshen, David; Jiang, Quan

2013-01-01

Background To overcome the limitations of conventional diffusion tensor magnetic resonance imaging resulting from the assumption of a Gaussian diffusion model for characterizing voxels containing multiple axonal orientations, Shannon's entropy was employed to evaluate white matter structure in human brain and in brain remodeling after traumatic brain injury (TBI) in a rat. Methods Thirteen healthy subjects were investigated using a Q-ball based DTI data sampling scheme. FA and entropy values were measured in white matter bundles, white matter fiber crossing areas, different gray matter (GM) regions and cerebrospinal fluid (CSF). Axonal densities' from the same regions of interest (ROIs) were evaluated in Bielschowsky and Luxol fast blue stained autopsy (n = 30) brain sections by light microscopy. As a case demonstration, a Wistar rat subjected to TBI and treated with bone marrow stromal cells (MSC) 1 week after TBI was employed to illustrate the superior ability of entropy over FA in detecting reorganized crossing axonal bundles as confirmed by histological analysis with Bielschowsky and Luxol fast blue staining. Results Unlike FA, entropy was less affected by axonal orientation and more affected by axonal density. A significant agreement (r = 0.91) was detected between entropy values from in vivo human brain and histologically measured axonal density from post mortum from the same brain structures. The MSC treated TBI rat demonstrated that the entropy approach is superior to FA in detecting axonal remodeling after injury. Compared with FA, entropy detected new axonal remodeling regions with crossing axons, confirmed with immunohistological staining. Conclusions Entropy measurement is more effective in distinguishing axonal remodeling after injury, when compared with FA. Entropy is also more sensitive to axonal density than axonal orientation, and thus may provide a more accurate reflection of axonal changes that occur in neurological injury and disease

Social reintegration of TBI patients: a solution to provide long-term support.

PubMed

Bulinski, Leszek

2010-01-01

This article evaluates the effectiveness of a workable long-term program to provide social support for TBI patients, based on the "Academy of Life" concept. Disability after TBI causes numerous disruptions of normal life, which affect the patient, the family, and society. The patient needs the particular kind of support the program was designed to provide. The study involved 200 married couples with a TBI spouse previously enrolled in the "Academy of Life." The methods included documentation analysis, clinical interviews, the Family Bonds Scale, the Social Isolation Scale, and the Social Functions subscale from a battery used to evaluate QOL after TBI. The subjects were examined before and after completing the program. In the first examination all types of family bonds were found to be severely weakened; there was deep social isolation, loneliness, sadness, a feeling of being surrounded by hostility, and no purposeful social activity. The most common form of support from significant others was pity and unwanted interference, accompanied by lack of understanding and social ostracism. In the second examination there was selective improvement of all parameters, significantly greater in patients without PTSD symptoms. The best effects were achieved in the reduction of social dysfunctions, the growth of purposeful social activity, and improvement in the type of support received, and a reduction of selected parameters of social isolation. The program here described is selectively effective for the social reintegration of TBI-patients, especially those without PTSD symptoms.

Contemporary imaging of mild TBI: the journey toward diffusion tensor imaging to assess neuronal damage.

PubMed

Fox, W Christopher; Park, Min S; Belverud, Shawn; Klugh, Arnett; Rivet, Dennis; Tomlin, Jeffrey M

2013-04-01

To follow the progression of neuroimaging as a means of non-invasive evaluation of mild traumatic brain injury (mTBI) in order to provide recommendations based on reproducible, defined imaging findings. A comprehensive literature review and analysis of contemporary published articles was performed to study the progression of neuroimaging findings as a non-invasive 'biomarker' for mTBI. Multiple imaging modalities exist to support the evaluation of patients with mTBI, including ultrasound (US), computed tomography (CT), single photon emission computed tomography (SPECT), positron emission tomography (PET), and magnetic resonance imaging (MRI). These techniques continue to evolve with the development of fractional anisotropy (FA), fiber tractography (FT), and diffusion tensor imaging (DTI). Modern imaging techniques, when applied in the appropriate clinical setting, may serve as a valuable tool for diagnosis and management of patients with mTBI. An understanding of modern neuroanatomical imaging will enhance our ability to analyse injury and recognize the manifestations of mTBI.

Age-Related Differences in Diagnostic Accuracy of Plasma GFAP and Tau For Identifying Acute Intracranial Trauma on CT: A TRACK-TBI Study.

PubMed

Gardner, Raquel C; Rubenstein, Richard; Wang, Kevin K W; Korley, Frederick Kofi; Yue, John K; Yuh, Esther Lim; Mukherjee, Pratik; Valadka, Alex; Okonkwo, David O; Diaz-Arrastia, Ramon; Manley, Geoffrey

2018-05-02

Plasma tau and glial fibrillary acidic protein (GFAP) are promising biomarkers for identifying traumatic brain injury (TBI) patients with intracranial trauma on CT. Accuracy in older adults with mild TBI (mTBI), the fastest growing TBI population, is unknown. Our aim was to assess for age-related differences in diagnostic accuracy of plasma tau and GFAP for identifying intracranial trauma on CT. Samples from 169 patients (age <40y [n=79], age 40-59y [n=60], age 60y+ [n=30]), a subset of patients from the TRACK-TBI Pilot study, who presented with mTBI (GCS 13-15), received head CT, and consented to blood-draw within 24h of injury were assayed for hyperphosphorylated-tau (P-tau), total-tau (T-tau; both via amplification-linked enhanced immunoassay using multi-arrayed fiberoptics), and GFAP (via sandwich enzyme-linked immunosorbent assay). P-tau, T-tau, P-tau:T-tau ratio, and GFAP concentration were significantly associated with CT findings. Overall, discriminative ability declined with increasing age for all assays, but this decline was only statistically significant for GFAP (area under the receiver operating characteristic curve [AUC]: old 0.73[ref] vs. young 0.93[p=0.037] or middle-aged 0.92[p<0.050]). P-tau concentration showed consistently highest diagnostic accuracy across all age-groups (AUC: old 0.84[ref] vs. young 0.95[p=0.274] or middle-aged 0.93[p=0.367]). Comparison of models including P-tau alone versus P-tau plus GFAP revealed significant added value of GFAP. In conclusion, the GFAP assay was less accurate for identifying intracranial trauma on CT among older versus younger mTBI patients. Mechanisms of this age-related difference, including role of assay methodology, specific TBI neuroanatomy, pre-existing conditions, and anti-thrombotic use warrant further study.

Impact of Aromatase Genetic Variation on Hormone Levels and Global Outcome after Severe TBI

PubMed Central

Garringer, Julie A.; Niyonkuru, Christian; McCullough, Emily H.; Loucks, Tammy; Dixon, C. Edward; Conley, Yvette P.; Berga, Sarah

2013-01-01

Abstract Although experimental traumatic brain injury (TBI) studies support estradiol as a neuroprotectant and potent stimulator of neuroplasticity, clinical studies suggest a negative association between endogenous estradiol profiles and mortality/poor outcomes. However, no studies have evaluated associations with cerebral spinal fluid (CSF) hormone profiles and aromatase gene (cytochrome P450 [CYP]19A1) variability on clinical TBI outcomes. We evaluated 110 adults with severe TBI. Average and daily estradiol, testosterone, and estradiol/testosterone ratios (E2:T) were measured using CSF and serum samples and compared to healthy controls. Eighteen tagging and four functional single-nucleotide polymorphisms (SNPs) for CYP19A1 were genotyped and compared to hormones, acute mortality, and Glasgow Outcome Scale (GOS) scores 6 months post-TBI. TBI subjects had lower CSF estradiol over time versus controls. CSF testosterone was initially high, but declined over time. E2/T ratios were initially low, compared to controls, but rose over time. Higher mean E2/T ratio in bivariate analysis was associated with lower mortality (p=0.019) and better GOS-6 scores (p=0.030). rs2470152 influenced CSF E2/T ratio and also serum and CSF testosterone (p≤0.05 all comparisons). Multiple-risk SNPs rs2470152, rs4646, and rs2470144 were associated with worse GOS-6 scores (p≤0.05, all comparisons), and those with>1 risk SNP variant had a higher risk for poor outcome, compared with those with ≤1 risk variant. TBI results in low CSF estradiol and dynamic CSF testosterone and E2/T ratio. In contrast to clinical serum hormone studies, higher CSF E2/T ratio was associated with better outcome. Further, genetic variation in CYP19A1 influences both hormone dynamics and outcome post-TBI. PMID:23540392

The Power of Cross-Disciplinary Teams for Developing First Responder Training in TBI

ERIC Educational Resources Information Center

Shackelford, Jo L.; Cappiccie, Amy

2016-01-01

Misunderstanding of the symptoms of traumatic brain injury (TBI) often leaves first responders ill-equipped to handle encounters involving subjects with brain injury. This paper details a cross-disciplinary project to develop and disseminate a training curriculum designed to increase first responders' knowledge of and skills with TBI survivors.…

Selling the story: narratives and charisma in adults with TBI.

PubMed

Jones, Corinne A; Turkstra, Lyn S

2011-01-01

To examine storytelling performance behaviours in adults with traumatic brain injury (TBI) and relate these behaviours to perceived charisma and desirability as a conversation partner. Seven adult males with traumatic brain injury (TBI) told their accident narratives to a male confederate. Ten male undergraduate students rated 1-minute video clips from the beginning of each narrative using the Charismatic Leadership Communication Scale (CLCS). Raters also indicated whether or not they would like to engage in conversation with each participant. Of the performative behaviours analysed, gestures alone significantly influenced CLCS ratings and reported likelihood of engaging in future conversation with the participant. Post-hoc analysis revealed that speech rate was significantly correlated with all of the preceding measures. There was a significant correlation between self- and other-ratings of charisma. The findings suggest that aspects of non-verbal performance, namely gesture use and speech rate, influence how charismatic an individual is perceived to be and how likely someone is to engage in conversation with that person. Variability in these performance behaviours may contribute to the variation in social outcomes seen in the TBI population.

Psychometric properties of the Multidimensional Assessment of Fatigue scale in traumatic brain injury: an NIDRR Traumatic Brain Injury Model Systems study.

PubMed

Lequerica, Anthony; Bushnik, Tamara; Wright, Jerry; Kolakowsky-Hayner, Stephanie A; Hammond, Flora M; Dijkers, Marcel P; Cantor, Joshua

2012-01-01

To investigate the psychometric properties of the Multidimensional Assessment of Fatigue (MAF) scale in a traumatic brain injury (TBI) sample. Prospective survey study. Community. One hundred sixty-seven individuals with TBI admitted for inpatient rehabilitation, enrolled into the TBI Model Systems national database, and followed up at either the first or second year postinjury. Not applicable. Multidimensional Assessment of Fatigue. The initial analysis, using items 1 to 14, which are based on a 10-point rating scale, found that only 1 item ("walking") misfit the overall construct of fatigue in this TBI population. However, this 10-point rating scale was found to have disordered thresholds. When ratings were collapsed into 4 response categories, all MAF items used to calculate the Global Fatigue Index formed a unidimensional scale. Findings generally support the unidimensionality of the MAF when used in a TBI population but call into question the use of a 10-point rating scale for items 1 to 14. Further study is needed to investigate the use of a 4-category rating scale across all items and the fit of the "walking" item for a measure of fatigue among individuals with TBI.

Sex differences in orbitofrontal connectivity in male and female veterans with TBI.

PubMed

McGlade, Erin; Rogowska, Jadwiga; Yurgelun-Todd, Deborah

2015-09-01

More female soldiers are now serving in combat theaters than at any other time. However, little is known about possible sex differences underlying the neuropathology and manifestation of one of modern war's signature injuries, traumatic brain injury (TBI). The paucity of information regarding sex differences in TBI is particularly evident when examining changes in executive function and emotion regulation associated with post concussive events. The current study objective was to observe whether patterns of orbitofrontal (OFC) functional connectivity would differ between female veterans with TBI and their male counterparts. The study further sought to determine whether OFC connectivity might be differentially associated with clinical measures of aggression and hostility. Seventeen female veterans and 24 male veterans, age 18 to 25, who met criteria for TBI completed resting state magnetic resonance imaging (MRI) and clinical assessment measures. Imaging data were analyzed using left and right seed regions of the OFC, and regression analyses were conducted to observe the relationship between resting state connectivity and self-reported aggression. Females and males in this study differed in OFC connectivity, with females demonstrating greater connectivity between left and right OFC and parietal and occipital regions and males demonstrating greater connectivity between left and right OFC and frontal and temporal regions. Significant associations between resting state connectivity and clinical measures were found only in male veterans. These findings suggest that TBI may interact with sex-specific patterns of brain connectivity in male and female veterans and exert divergent effects on clinical profiles of aggression post-injury.

TBI-ROC Part Seven: Traumatic Brain Injury--Technologies to Support Memory and Cognition

ERIC Educational Resources Information Center

Scherer, Marcia; Elias, Eileen; Weider, Katie

2010-01-01

This article is the seventh of a multi-part series on traumatic brain injury (TBI). The six earlier articles in this series have discussed the individualized nature of TBI and its consequences, the rehabilitation continuum, and interventions at various points along the continuum. As noted throughout the articles, many individuals with TBI…

Reliability of a computer and Internet survey (Computer User Profile) used by adults with and without traumatic brain injury (TBI).

PubMed

Kilov, Andrea M; Togher, Leanne; Power, Emma

2015-01-01

To determine test-re-test reliability of the 'Computer User Profile' (CUP) in people with and without TBI. The CUP was administered on two occasions to people with and without TBI. The CUP investigated the nature and frequency of participants' computer and Internet use. Intra-class correlation coefficients and kappa coefficients were conducted to measure reliability of individual CUP items. Descriptive statistics were used to summarize content of responses. Sixteen adults with TBI and 40 adults without TBI were included in the study. All participants were reliable in reporting demographic information, frequency of social communication and leisure activities and computer/Internet habits and usage. Adults with TBI were reliable in 77% of their responses to survey items. Adults without TBI were reliable in 88% of their responses to survey items. The CUP was practical and valuable in capturing information about social, leisure, communication and computer/Internet habits of people with and without TBI. Adults without TBI scored more items with satisfactory reliability overall in their surveys. Future studies may include larger samples and could also include an exploration of how people with/without TBI use other digital communication technologies. This may provide further information on determining technology readiness for people with TBI in therapy programmes.

Correspondence of the Boston Assessment of Traumatic Brain Injury-Lifetime (BAT-L) clinical interview and the VA TBI screen.

PubMed

Fortier, Catherine Brawn; Amick, Melissa M; Kenna, Alexandra; Milberg, William P; McGlinchey, Regina E

2015-01-01

Mild traumatic brain injury is the signature injury of Operation Enduring Freedom (OEF), Operation Iraqi Freedom (OIF), and Operation New Dawn (OND), yet its identification and diagnosis is controversial and fraught with challenges. In 2007, the Department of Veterans Affairs (VA) implemented a policy requiring traumatic brain injury (TBI) screening on all individuals returning from deployment in the OEF/OIF/OND theaters of operation that lead to the rapid and widespread use of the VA TBI screen. The Boston Assessment of TBI-Lifetime (BAT-L) is the first validated, postcombat semistructured clinical interview to characterize head injuries and diagnose TBIs throughout the life span, including prior to, during, and post-military service. Community-dwelling convenience sample of 179 OEF/OIF/OND veterans. BAT-L, VA TBI screen. Based on BAT-L diagnosis of military TBI, the VA TBI screen demonstrated similar sensitivity (0.85) and specificity (0.82) when administered by research staff. When BAT-L diagnosis was compared with historical clinician-administered VA TBI screen in a subset of participants, sensitivity was reduced. The specificity of the research-administered VA TBI screen was more than adequate. The sensitivity of the VA TBI screen, although relatively high, suggests that it does not oversample or "catch all" possible military TBIs. Traumatic brain injuries identified by the BAT-L, but not identified by the VA TBI screen, were predominantly noncombat military injuries. There is potential concern regarding the validity and reliability of the clinician administered VA TBI screen, as we found poor correspondence between it and the BAT-L, as well as low interrater reliability between the clinician-administered and research-administered screen.

Predictive factors for 1-year outcome of a cohort of patients with severe traumatic brain injury (TBI): results from the PariS-TBI study.

PubMed

Jourdan, C; Bosserelle, V; Azerad, S; Ghout, I; Bayen, E; Aegerter, P; Weiss, J J; Mateo, J; Lescot, T; Vigué, B; Tazarourte, K; Pradat-Diehl, P; Azouvi, P

2013-01-01

To assess outcome and predicting factors 1 year after a severe traumatic brain injury (TBI). Multi-centre prospective inception cohort study of patients aged 15 or older with a severe TBI in the Parisian area, France. Data were collected prospectively starting the day of injury. One-year evaluation included the relatives-rating of the Dysexecutive Questionnaire (DEX-R), the Glasgow Outcome Scale-Extended (GOSE) and employment. Univariate and multivariate tests were computed. Among 257 survivors, 134 were included (mean age 36 years, 84% men). Good recovery concerned 19%, moderate disability 43% and severe disability 38%. Among patients employed pre-injury, 42% were working, 28% with no job change. DEX-R score was significantly associated with length of education only. Among initial severity measures, only the IMPACT prognostic score was significantly related to GOSE in univariate analyses, while measures relating to early evolution were more significant predictors. In multivariate analyses, independent predictors of GOSE were length of stay in intensive care (LOS), age and education. Independent predictors of employment were LOS and age. Age, education and injury severity are independent predictors of global disability and return to work 1 year after a severe TBI.

Electropalatographic (EPG) Assessment of Tongue-to-Palate Contacts in Dysarthric Speakers Following TBI

ERIC Educational Resources Information Center

Kuruvilla, Mili S.; Murdoch, Bruce E.; Goozee, Justine V.

2008-01-01

The aim of the investigation was to compare EPG-derived spatial and timing measures between a group of 11 dysarthric individuals post-severe TBI and 10 age- and sex-matched neurologically non-impaired individuals. Participants of the TBI group were diagnosed with dysarthria ranging from mild-to-moderate-severe dysarthria. Each participant from the…

Molecular Signatures and Diagnostic Biomarkers of Cumulative, Blast-Graded Mild TBI

DTIC Science & Technology

2012-10-01

These results are in agreement with data obtained using non-blast TBI models (Diet- rich et al., 2004; Maegele et al., 2007). Moreover, CX3CL1 chemokine...the shoulder at Figure 1A), substantially contaminating the blast wave in the direction of shock tube axis (Figure 1A). In addition, the exhaust...highly spe- cific for the CNS and is present in platelets and red blood cells (see Svetlov et al., 2009 for review). In previous studies, we reported a

Comparison of FIM™ communication ratings for English versus non-English speakers in the traumatic brain injury model systems (TBIMS) national database.

PubMed

Lequerica, Anthony; Krch, Denise; Lengenfelder, Jean; Chiaravalloti, Nancy; Arango-Lasprilla, Juan Carlos; Hammond, Flora M; O'Neil-Pirozzi, Therese M; Perrin, Paul B; Sander, Angelle M

2015-01-01

To examine the effect of primary language on admission and discharge FIM™ communication ratings in a sample of individuals with moderate-to-severe traumatic brain injury (TBI). Secondary data analysis of rehabilitation admission and discharge FIM™ communication ratings of 2795 individuals hospitalized at a Traumatic Brain Injury Model Systems (TBIMS) centre between 2007-2012. Individuals who spoke no English were rated worse on functional communication outcomes at inpatient rehabilitation discharge relative to individuals whose primary language was English. These findings may reflect systematic bias in FIM™ communication ratings of non-English-speaking individuals with TBI and/or TBI-induced communication difficulties in non-English-speaking individuals. Clinical and research implications are discussed.

Cognitive ability predicts motor learning on a virtual reality game in patients with TBI.

PubMed

O'Neil, Rochelle L; Skeel, Reid L; Ustinova, Ksenia I

2013-01-01

Virtual reality games and simulations have been utilized successfully for motor rehabilitation of individuals with traumatic brain injury (TBI). Little is known, however, how TBI-related cognitive decline affects learning of motor tasks in virtual environments. To fill this gap, we examined learning within a virtual reality game involving various reaching motions in 14 patients with TBI and 15 healthy individuals with different cognitive abilities. All participants practiced ten 90-second gaming trials to assess various aspects of motor learning. Cognitive abilities were assessed with a battery of tests including measures of memory, executive functioning, and visuospatial ability. Overall, participants with TBI showed both reduced performance and a slower learning rate in the virtual reality game compared to healthy individuals. Numerous correlations between overall performance and several of the cognitive ability domains were revealed for both the patient and control groups, with the best predictor being overall cognitive ability. The results may provide a starting point for rehabilitation programs regarding which cognitive domains interact with motor learning.

Regional CBF in chronic stable TBI treated with hyperbaric oxygen.

PubMed

Barrett, K F; Masel, B; Patterson, J; Scheibel, R S; Corson, K P; Mader, J T

2004-01-01

To investigate whether Hyperbaric Oxygen Therapy (HBO2) could improve neurologic deficits and regional cerebral blood flow (rCBF) in chronic traumatic brain injuries (TBI), the authors employed a nonrandomized control pilot trial. Five subjects, at least three years post head injury, received HBO2. Five head injured controls (HIC) were matched for age, sex, and type of injury. Five healthy subjects served as normal controls. Sixty-eight normal volunteers comprised a reference data bank against which to compare SPECT brain scans. HBO2 subjects received 120 HBO2 in blocks of 80 and 40 treatments with an interval five-month break. Normal controls underwent a single SPECT brain scan, HBO2, and repeat SPECT battery. TBI subjects were evaluated by neurologic, neuropsychometric, exercise testing, and pre and post study MRIs, or CT scans if MRI was contraindicated. Statistical Parametric Mapping was applied to SPECT scans for rCBF analysis. There were no significant objective changes in neurologic, neuropsychometric, exercise testing, MRIs, or rCBF. In this small pilot study, HBO2 did not effect clinical or regional cerebral blood flow improvement in TBI subjects.

Selling the story: Narratives and charisma in adults with TBI

PubMed Central

JONES, CORINNE A.; TURKSTRA, LYN S.

2015-01-01

Objective To examine storytelling performance behaviours in adults with traumatic brain injury (TBI) and relate these behaviours to perceived charisma and desirability as a conversation partner. Design and methods Seven adult males with traumatic brain injury (TBI) told their accident narratives to a male confederate. Ten male undergraduate students rated 1-minute video clips from the beginning of each narrative using the Charismatic Leadership Communication Scale (CLCS). Raters also indicated whether or not they would like to engage in conversation with each participant. Results Of the performative behaviours analysed, gestures alone significantly influenced CLCS ratings and reported likelihood of engaging in future conversation with the participant. Post-hoc analysis revealed that speech rate was significantly correlated with all of the preceding measures. There was a significant correlation between self- and other-ratings of charisma. Conclusions The findings suggest that aspects of non-verbal performance, namely gesture use and speech rate, influence how charismatic an individual is perceived to be and how likely someone is to engage in conversation with that person. Variability in these performance behaviours may contribute to the variation in social outcomes seen in the TBI population. PMID:21714624

Monitoring Neurocognitive Performance and Electrophysiological Activity After Mild Traumatic Brain Injury (mTBI)

DTIC Science & Technology

2014-03-01

return to duty’ decisions. 15. SUBJECT TERMS Traumatic Brain Injury, mTBI, concussion, Magnetoencephalography, MEG , MRI, biomarkers, actigraphy 16...within approximately two years of the writing of this report. 3. KEYWORDS Traumatic Brain Injury, mTBI, concussion, Magnetoencephalography, MEG , MRI...Merrifield, PhD) i. Magnetoencephalography ( MEG ) laboratory is fully operational after two weeks of cool down and testing in February 2014. Pilot testing

A case–control study examining whether neurological deficits and PTSD in combat veterans are related to episodes of mild TBI

PubMed Central

Riechers, Ronald George; Wang, Xiao-Feng; Piero, Traci; Ruff, Suzanne Smith

2012-01-01

Background Mild traumatic brain injury (mTBI) is a common injury among military personnel serving in Iraq or Afghanistan. The impact of repeated episodes of combat mTBI is unknown. Objective To evaluate relationships among mTBI, post-traumatic stress disorder (PTSD) and neurological deficits (NDs) in US veterans who served in Iraq or Afghanistan. Methods This was a case–control study. From 2091 veterans screened for traumatic brain injury, the authors studied 126 who sustained mTBI with one or more episodes of loss of consciousness (LOC) in combat. Comparison groups: 21 combat veterans who had definite or possible episodes of mTBI without LOC and 21 veterans who sustained mTBI with LOC as civilians. Results Among combat veterans with mTBI, 52% had NDs, 66% had PTSD and 50% had PTSD and an ND. Impaired olfaction was the most common ND, found in 65 veterans. The prevalence of an ND or PTSD correlated with the number of mTBI exposures with LOC. The prevalence of an ND or PTSD was >90% for more than five episodes of LOC. Severity of PTSD and impairment of olfaction increased with number of LOC episodes. The prevalence of an ND for the 34 combat veterans with one episode of LOC (4/34=11.8%) was similar to that of the 21 veterans of similar age and educational background who sustained civilian mTBI with one episode of LOC (2/21=9.5%, p-NS). Conclusions Impaired olfaction was the most frequently recognised ND. Repeated episodes of combat mTBI were associated with increased likelihood of PTSD and an ND. Combat setting may not increase the likelihood of an ND. Two possible connections between mTBI and PTSD are (1) that circumstances leading to combat mTBI likely involve severe psychological trauma and (2) that altered cerebral functioning following mTBI may increase the likelihood that a traumatic event results in PTSD. PMID:22431700

Treatment adherence in cognitive processing therapy for combat-related PTSD with history of mild TBI.

PubMed

Davis, Jeremy J; Walter, Kristen H; Chard, Kathleen M; Parkinson, R Bruce; Houston, Wes S

2013-02-01

This retrospective study examined treatment adherence in Cognitive Processing Therapy (CPT) for combat-related posttraumatic stress disorder (PTSD) in Veterans of Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) with and without history of mild traumatic brain injury (mTBI). Medical record review of consecutive referrals to an outpatient PTSD clinic identified veterans diagnosed with combat-related PTSD who began treatment with CPT. The sample (N = 136) was grouped according to positive (n = 44) and negative (n = 92) mTBI history. Groups were compared in terms of presenting symptoms and treatment adherence. The groups were not different on a pretreatment measure of depression, but self-reported and clinician-rated PTSD symptoms were higher in veterans with history of mTBI. The treatment completion rate was greater than 61% in both groups. The number of sessions attended averaged 9.6 for the PTSD group and 7.9 for the mTBI/PTSD group (p = .05). Given the lack of marked group differences in treatment adherence, these initial findings suggest that standard CPT for PTSD may be a tolerable treatment for OEF/OIF veterans with a history of PTSD and mTBI as well as veterans with PTSD alone.

The ties that bind: the relationship between caregiver burden and the neuropsychological functioning of TBI survivors.

PubMed

Lehan, Tara; Arango-Lasprilla, Juan Carlos; de los Reyes, Carlos José; Quijano, María Cristina

2012-01-01

Advances in medical and assistive technology have increased the likelihood of survival following a traumatic brain injury (TBI). Consequently, families frequently must provide care to individuals with TBI. Because they are rarely prepared for the associated demanding medical needs and financial burden, family caregivers are at risk for physical and emotional problems, which can negatively influence their individual and family functioning. Whereas scholars have examined the influence of survivor functioning on caregiver burden, few have explicitly recognized that caregiver burden also influences survivor functioning. Results of a multivariate linear regression suggest that, in a sample of 51 pairs of TBI survivors and their caregivers living in Colombia, survivors receiving care from a family member who reported a higher level of burden had poorer objective neuropsychological functioning than those receiving care from a family member who reported a lower level of burden, after controlling for survivor education and history of occupational therapy. Therefore, a family-focused approach might maximize intervention effectiveness, especially for Latin American and Hispanic families, which tend to be characterized by a strong sense of familism. The emphasis on family can create problems in a healthcare system that views the individual as the primary unit.

Review of the literature on the use of social media by people with traumatic brain injury (TBI).

PubMed

Brunner, Melissa; Hemsley, Bronwyn; Palmer, Stuart; Dann, Stephen; Togher, Leanne

2015-01-01

To review the literature relating to use of social media by people with a traumatic brain injury (TBI), specifically its use for social engagement, information exchange or rehabilitation. A systematic review with a qualitative meta-synthesis of content themes was conducted. In June 2014, 10 databases were searched for relevant, peer-reviewed research studies in English that related to both TBI and social media. Sixteen studies met the inclusion criteria, with Facebook™ and Twitter™ being the most common social media represented in the included studies. Content analysis identified three major categories of meaning in relation to social media and TBI: (1) risks and benefits; (2) barriers and facilitators; and (3) purposes of use of social media. A greater emphasis was evident regarding potential risks and apparent barriers to social media use, with little focus on facilitators of successful use by people with TBI. Research to date reveals a range of benefits to the use of social media by people with TBI however there is little empirical research investigating its use. Further research focusing on ways to remove the barriers and increase facilitators for the use of social media by people with TBI is needed.

Longitudinal Examination of Resilience After Traumatic Brain Injury: A Traumatic Brain Injury Model Systems Study.

PubMed

Marwitz, Jennifer H; Sima, Adam P; Kreutzer, Jeffrey S; Dreer, Laura E; Bergquist, Thomas F; Zafonte, Ross; Johnson-Greene, Douglas; Felix, Elizabeth R

2018-02-01

To evaluate (1) the trajectory of resilience during the first year after a moderate-severe traumatic brain injury (TBI); (2) factors associated with resilience at 3, 6, and 12 months postinjury; and (3) changing relationships over time between resilience and other factors. Longitudinal analysis of an observational cohort. Five inpatient rehabilitation centers. Patients with TBI (N=195) enrolled in the resilience module of the TBI Model Systems study with data collected at 3-, 6-, and 12-month follow-up. Not applicable. Connor-Davidson Resilience Scale. Initially, resilience levels appeared to be stable during the first year postinjury. Individual growth curve models were used to examine resilience over time in relation to demographic, psychosocial, and injury characteristics. After adjusting for these characteristics, resilience actually declined over time. Higher levels of resilience were related to nonminority status, absence of preinjury substance abuse, lower anxiety and disability level, and greater life satisfaction. Resilience is a construct that is relevant to understanding brain injury outcomes and has potential value in planning clinical interventions. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Quantitative Tractography and Volumetric MRI in Blast and Blunt Force TBI: Predictors of Neurocognitive and Behavioral Outcome

DTIC Science & Technology

2013-10-01

veterans with mTBI. Further, presence of post-traumatic amnesia may affect subtype of fatigue experienced by veterans with mTBI. The fornix, a limbic...physical fatigue, but not cognitive fatigue, were associated with the presence of post-traumatic amnesia at injury. Conclusion: The MFIS is a valid...pathways. Cognitive and Psychiatric Dissociations between Fractional Anisotropy and Cortical Thickness in Veterans with Mild TBI: (Scott Sorg, Mark

Clinical Utility and Psychometric Properties of the Traumatic Brain Injury Quality of Life Scale (TBI-QOL) in US Military Service Members.

PubMed

Lange, Rael T; Brickell, Tracey A; Bailie, Jason M; Tulsky, David S; French, Louis M

2016-01-01

To examine the clinical utility and psychometric properties of the Traumatic Brain Injury Quality of Life (TBI-QOL) scale in a US military population. One hundred fifty-two US military service members (age: M = 34.3, SD = 9.4; 89.5% men) prospectively enrolled from the Walter Reed National Military Medical Center and other nationwide community outreach initiatives. Participants included 99 service members who had sustained a mild traumatic brain injury (TBI) and 53 injured or noninjured controls without TBI (n = 29 and n = 24, respectively). Participants completed the TBI-QOL scale and 5 other behavioral measures, on average, 33.8 months postinjury (SD = 37.9). Fourteen TBI-QOL subscales; Neurobehavioral Symptom Inventory; Posttraumatic Stress Disorder Checklist-Civilian version; Alcohol Use Disorders Identification Test; Combat Exposure Scale. The internal consistency reliability of the TBI-QOL scales ranged from α = .91 to α = .98. The convergent and discriminant validity of the 14 TBI-QOL subscales was high. The mild TBI group had significantly worse scores on 10 of the 14 TBI-QOL subscales than the control group (range, P < .001 to P = .043). Effect sizes ranged from medium to very large (d = 0.35 to d = 1.13). The largest differences were found on the Cognition-General Concerns (d = 1.13), Executive Function (d = 0.94), Grief-Loss (d = 0.88), Pain Interference (d = 0.83), and Headache Pain (d = 0.83) subscales. These results support the use of the TBI-QOL scale as a measure of health-related quality of life in a mild TBI military sample. Additional research is recommended to further evaluate the clinical utility of the TBI-QOL scale in both military and civilian settings.

Early coagulation events induce acute lung injury in a rat model of blunt traumatic brain injury.

PubMed

Yasui, Hideki; Donahue, Deborah L; Walsh, Mark; Castellino, Francis J; Ploplis, Victoria A

2016-07-01

Acute lung injury (ALI) and systemic coagulopathy are serious complications of traumatic brain injury (TBI) that frequently lead to poor clinical outcomes. Although the release of tissue factor (TF), a potent initiator of the extrinsic pathway of coagulation, from the injured brain is thought to play a key role in coagulopathy after TBI, its function in ALI following TBI remains unclear. In this study, we investigated whether the systemic appearance of TF correlated with the ensuing coagulopathy that follows TBI in ALI using an anesthetized rat blunt trauma TBI model. Blood and lung samples were obtained after TBI. Compared with controls, pulmonary edema and increased pulmonary permeability were observed as early as 5 min after TBI without evidence of norepinephrine involvement. Systemic TF increased at 5 min and then diminished 60 min after TBI. Lung injury and alveolar hemorrhaging were also observed as early as 5 min after TBI. A biphasic elevation of TF was observed in the lungs after TBI, and TF-positive microparticles (MPs) were detected in the alveolar spaces. Fibrin(ogen) deposition was also observed in the lungs within 60 min after TBI. Additionally, preadministration of a direct thrombin inhibitor, Refludan, attenuated lung injuries, thus implicating thrombin as a direct participant in ALI after TBI. The results from this study demonstrated that enhanced systemic TF may be an initiator of coagulation activation that contributes to ALI after TBI. Copyright © 2016 the American Physiological Society.

Very late nonfatal consequences of fractionated TBI in children undergoing bone marrow transplant

DOE Office of Scientific and Technical Information (OSTI.GOV)

Faraci, Maura; Barra, Salvina; Cohen, Amnon

Purpose: To describe long-term late consequences in children who received total body irradiation (TBI) for hematopoietic stem cell transplantation 10 years earlier. Methods and Materials: A cohort of 42 children treated with TBI between 1985 and 1993, still alive at least 10 years after fractionated TBI (FTBI), was evaluated. Twenty-five patients received FTBI at 330 cGy/day for 3 days (total dose 990 cGy), whereas 17 children were administered fractions of 200 cGy twice daily for 3 days (total dose 1200 cGy). Twenty-seven patients received autologous and 16 allogeneic hematopoietic stem cell transplantation. Median age at TBI was 6.3 years, andmore » 18.4 years at most recent follow-up. Results: Cataract was diagnosed in 78% of patients after a median of 5.7 years. Hypothyroidism was detected in 12%, whereas thyroid nodules were observed in 60% of our population after a median interval of 10.2 years. Patients treated with 990 cGy developed thyroid nodules more frequently than those treated with 1200 cGy (p = 0.0002). Thyroid carcinoma was diagnosed in 14% of the total population. Females who received FTBI after menarche more frequently developed temporary ovarian dysfunction than those treated before menarche, but cases of persistent ovarian dysfunction did not differ between the two groups. Indirect signs of germinal testicular dysfunction were detected in 87% of males. Restrictive pulmonary disease was observed in 74% of patients. Osteochondroma was found in 29% of patients after a median interval of 9.2 years. This latter complication appeared more frequently in patients irradiated before the age of 3 years (p < 0.001). Conclusions: This study shows that late effects that are likely permanent, although not fatal, are frequent in survivors 10 years after TBI. However, some of the side effects observed shortly after TBI either disappeared or remained unchanged without signs of evolution. Monitoring is recommended to pursue secondary prevention strategies and

Very late nonfatal consequences of fractionated TBI in children undergoing bone marrow transplant.

PubMed

Faraci, Maura; Barra, Salvina; Cohen, Amnon; Lanino, Edoardo; Grisolia, Francesca; Miano, Maurizio; Foppiano, Franca; Sacco, Oliviero; Cabria, Manlio; De Marco, Riccardo; Stella, Gilberto; Dallorso, Sandro; Bagnasco, Francesca; Vitale, Vito; Dini, Giorgio; Haupt, Riccardo

2005-12-01

To describe long-term late consequences in children who received total body irradiation (TBI) for hematopoietic stem cell transplantation 10 years earlier. A cohort of 42 children treated with TBI between 1985 and 1993, still alive at least 10 years after fractionated TBI (FTBI), was evaluated. Twenty-five patients received FTBI at 330 cGy/day for 3 days (total dose 990 cGy), whereas 17 children were administered fractions of 200 cGy twice daily for 3 days (total dose 1200 cGy). Twenty-seven patients received autologous and 16 allogeneic hematopoietic stem cell transplantation. Median age at TBI was 6.3 years, and 18.4 years at most recent follow-up. Cataract was diagnosed in 78% of patients after a median of 5.7 years. Hypothyroidism was detected in 12%, whereas thyroid nodules were observed in 60% of our population after a median interval of 10.2 years. Patients treated with 990 cGy developed thyroid nodules more frequently than those treated with 1200 cGy (p = 0.0002). Thyroid carcinoma was diagnosed in 14% of the total population. Females who received FTBI after menarche more frequently developed temporary ovarian dysfunction than those treated before menarche, but cases of persistent ovarian dysfunction did not differ between the two groups. Indirect signs of germinal testicular dysfunction were detected in 87% of males. Restrictive pulmonary disease was observed in 74% of patients. Osteochondroma was found in 29% of patients after a median interval of 9.2 years. This latter complication appeared more frequently in patients irradiated before the age of 3 years (p < 0.001). This study shows that late effects that are likely permanent, although not fatal, are frequent in survivors 10 years after TBI. However, some of the side effects observed shortly after TBI either disappeared or remained unchanged without signs of evolution. Monitoring is recommended to pursue secondary prevention strategies and counseling on family planning.

Assessment and rehabilitation of central sensory impairments for balance in mTBI using auditory biofeedback: a randomized clinical trial.

PubMed

Fino, Peter C; Peterka, Robert J; Hullar, Timothy E; Murchison, Chad; Horak, Fay B; Chesnutt, James C; King, Laurie A

2017-02-23

Complaints of imbalance are common non-resolving signs in individuals with post-concussive syndrome. Yet, there is no consensus rehabilitation for non-resolving balance complaints following mild traumatic brain injury (mTBI). The heterogeneity of balance deficits and varied rates of recovery suggest varied etiologies and a need for interventions that address the underlying causes of poor balance function. Our central hypothesis is that most chronic balance deficits after mTBI result from impairments in central sensorimotor integration that may be helped by rehabilitation. Two studies are described to 1) characterize balance deficits in people with mTBI who have chronic, non-resolving balance deficits compared to healthy control subjects, and 2) determine the efficacy of an augmented vestibular rehabilitation program using auditory biofeedback to improve central sensorimotor integration, static and dynamic balance, and functional activity in patients with chronic mTBI. Two studies are described. Study 1 is a cross-sectional study to take place jointly at Oregon Health and Science University and the VA Portland Health Care System. The study participants will be individuals with non-resolving complaints of balance following mTBI and age- and gender-matched controls who meet all inclusion criteria. The primary outcome will be measures of central sensorimotor integration derived from a novel central sensorimotor integration test. Study 2 is a randomized controlled intervention to take place at Oregon Health & Science University. In this study, participants from Study 1 with mTBI and abnormal central sensorimotor integration will be randomized into two rehabilitation interventions. The interventions will be 6 weeks of vestibular rehabilitation 1) with or 2) without the use of an auditory biofeedback device. The primary outcome measure is the daily activity of the participants measured using an inertial sensor. The results of these two studies will improve our

Routine repeat head CT may not be necessary for patients with mild TBI

PubMed Central

Rosen, Claire B; Luy, Diego D; Deane, Molly R; Scalea, Thomas M; Stein, Deborah M

2018-01-01

Background Routine repeat cranial CT (RHCT) is standard of care for CT-verified traumatic brain injury (TBI). Despite mixed evidence, those with mild TBI are subject to radiation and expense from serial CT scans. Thus, we investigated the necessity and utility of RHCT for patients with mild TBI. We hypothesized that repeat head CT in these patients would not alter patient care or outcomes. Methods We retrospectively studied patients suffering from mild TBI (Glasgow Coma Scale (GCS) score 13–15) and treated at the R Adams Cowley Shock Trauma Center from November 2014 through January 2015. The primary outcome was the need for surgical intervention. Outcomes were compared using paired Student’s t-test, and stratified by injury on initial CT, GCS change, demographics, and presenting vital signs (mean ± SD). Results Eighty-five patients met inclusion criteria with an average initial GCS score=14.6±0.57. Our center sees about 2800 patients with TBI per year, or about 230 per month. This includes patients with concussions. This sample represents about 30% of patients with TBI seen during the study period. Ten patients required operation (four based on initial CT and others for worsening GCS, headaches, large unresolving injury). There was progression of injury on repeat CT scan in only two patients that required operation, and this accompanied clinical deterioration. The mean brain Abbreviated Injury Scale (AIS) score was 4.8±0.3 for surgical patients on initial CT scan compared with 3.4±0.6 (P<0.001) for non-surgical patients. Initial CT subdural hematoma size was 1.1±0.6 cm for surgical patients compared with 0.49±0.3 cm (P=0.05) for non-surgical patients. There was no significant difference between intervention groups in terms of other intracranial injuries, demographics, vital signs, or change in GCS. Overall, 75 patients that did not require surgical intervention received RHCT. At $340 per CT, $51 000 was spent on unnecessary imaging ($367 000/year

Concussion in the Military: an Evidence-Base Review of mTBI in US Military Personnel Focused on Posttraumatic Headache.

PubMed

Holtkamp, Matthew D; Grimes, Jamie; Ling, Geoffrey

2016-06-01

Traumatic brain injury (TBI) is defined as an alteration in brain function caused by an external force. Mild TBI or concussion is now well recognized to be a risk of military service as well as participation in athletic sports such as football. Posttraumatic headache (PTH) is the most common symptom after mTBI in US service members. PTH most commonly presents with migraine-like headache features. The following is an overview of the epidemiology, pathophysiology, clinical course, prognosis, complications, and treatment of mTBI and associated comorbidities with a focus on PTH. There is a particular emphasis on emerging evidence-based clinical practice. One important medical consequence of the recognition that mTBI is a highly prevalent among military service members is that the Department of Defense (DoD) is dedicating significant financial and intellectual resources to better understanding and developing treatments for TBI. The identification of the importance of TBI among the US military population has had the added benefit of increasing awareness of this condition among civilian populations, particularly those engaged in both professional and youth sports. The NIH and NSF are also supporting important TBI research. President Obama's Brain Initiative is also providing additional impetus for these efforts. Unfortunately, the understanding of the acute and chronic effects of mTBI on the brain remains limited. Gratefully, there is hope that through innovative research, there will be advances in elucidating the underlying pathophysiology, which will lead to clinical and prognostic indicators, ultimately resulting in new treatment options for this very complicated set of disorders.

Risk-taking behaviors and impulsivity among veterans with and without PTSD and mild TBI.

PubMed

James, Lisa M; Strom, Thad Q; Leskela, Jennie

2014-04-01

Military personnel commonly experience post-traumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI), both of which are associated with premature mortality. The present study examined two factors that may play a role in premature mortality--impulsivity and risk-taking behaviors--in a sample of 234 veterans screening positive for PTSD, mTBI, PTSD + mTBI, and controls. Analyses of variance demonstrated that veterans with PTSD, regardless of mTBI status, reported engaging in more frequent risky behaviors and reported a greater tendency to engage in impulsive behaviors when in a negative affective state. They also reported more premilitary delinquent behaviors and more suicide-related behaviors than controls. The present study highlights associations between impulsivity, risk-taking behaviors, and PTSD, and suggests continuity across the lifespan in terms of a predisposition to engage in impulsive and/or risky behaviors. Thorough evaluation of impulsivity and potentially risky behaviors is important in clinical settings to guide interventions and reduce the mortality and public health impact of high-risk behaviors in veterans. Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.

Deep pockets or blueprint for change: traumatic brain injury (TBI) proactive strategy.

PubMed

Wood, D W; Pohl, S; Lawler, S; Okamoto, G

1998-09-01

The Pacific Conference scheduled for October 1-3, 1988, is a critical event in the development of an integrated community-based plan for a comprehensive continuum of services to address the "silent epidemic," Traumatic Brain Injured (TBI). This paper provides insights of the complex nature and the special problems faced by the TBI survivors; their families, natural supports and caregivers, as well as the health, social and educational care providers in Hawaii. Process for the development of the community plan is presented.

Improving Balance in TBI Using a Low-Cost Customized Virtual Reality Rehabilitation Tool

DTIC Science & Technology

2016-10-01

AWARD NUMBER: W81XWH-14-2-0150 TITLE: Improving Balance in TBI Using a Low-Cost Customized Virtual Reality Rehabilitation Tool PRINCIPAL...AND SUBTITLE Improving Balance in TBI Using a Low-Cost Customized Virtual Reality Rehabilitation Tool 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH...Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The proposed study will implement and evaluate a novel, low-cost, Virtual Reality (VR

Development of a 3D immersive videogame to improve arm-postural coordination in patients with TBI

PubMed Central

2011-01-01

Background Traumatic brain injury (TBI) disrupts the central and executive mechanisms of arm(s) and postural (trunk and legs) coordination. To address these issues, we developed a 3D immersive videogame-- Octopus. The game was developed using the basic principles of videogame design and previous experience of using videogames for rehabilitation of patients with acquired brain injuries. Unlike many other custom-designed virtual environments, Octopus included an actual gaming component with a system of multiple rewards, making the game challenging, competitive, motivating and fun. Effect of a short-term practice with the Octopus game on arm-postural coordination in patients with TBI was tested. Methods The game was developed using WorldViz Vizard software, integrated with the Qualysis system for motion analysis. Avatars of the participant's hands precisely reproducing the real-time kinematic patterns were synchronized with the simulated environment, presented in the first person 3D view on an 82-inch DLP screen. 13 individuals with mild-to-moderate manifestations of TBI participated in the study. While standing in front of the screen, the participants interacted with a computer-generated environment by popping bubbles blown by the Octopus. The bubbles followed a specific trajectory. Interception of the bubbles with the left or right hand avatar allowed flexible use of the postural segments for balance maintenance and arm transport. All participants practiced ten 90-s gaming trials during a single session, followed by a retention test. Arm-postural coordination was analysed using principal component analysis. Results As a result of the short-term practice, the participants improved in game performance, arm movement time, and precision. Improvements were achieved mostly by adapting efficient arm-postural coordination strategies. Of the 13 participants, 10 showed an immediate increase in arm forward reach and single-leg stance time. Conclusion These results support the

Development of a 3D immersive videogame to improve arm-postural coordination in patients with TBI.

PubMed

Ustinova, Ksenia I; Leonard, Wesley A; Cassavaugh, Nicholas D; Ingersoll, Christopher D

2011-10-31

Traumatic brain injury (TBI) disrupts the central and executive mechanisms of arm(s) and postural (trunk and legs) coordination. To address these issues, we developed a 3D immersive videogame--Octopus. The game was developed using the basic principles of videogame design and previous experience of using videogames for rehabilitation of patients with acquired brain injuries. Unlike many other custom-designed virtual environments, Octopus included an actual gaming component with a system of multiple rewards, making the game challenging, competitive, motivating and fun. Effect of a short-term practice with the Octopus game on arm-postural coordination in patients with TBI was tested. The game was developed using WorldViz Vizard software, integrated with the Qualysis system for motion analysis. Avatars of the participant's hands precisely reproducing the real-time kinematic patterns were synchronized with the simulated environment, presented in the first person 3D view on an 82-inch DLP screen. 13 individuals with mild-to-moderate manifestations of TBI participated in the study. While standing in front of the screen, the participants interacted with a computer-generated environment by popping bubbles blown by the Octopus. The bubbles followed a specific trajectory. Interception of the bubbles with the left or right hand avatar allowed flexible use of the postural segments for balance maintenance and arm transport. All participants practiced ten 90-s gaming trials during a single session, followed by a retention test. Arm-postural coordination was analysed using principal component analysis. As a result of the short-term practice, the participants improved in game performance, arm movement time, and precision. Improvements were achieved mostly by adapting efficient arm-postural coordination strategies. Of the 13 participants, 10 showed an immediate increase in arm forward reach and single-leg stance time. These results support the feasibility of using the custom-made 3D

Cognitive reserve and persistent post-concussion symptoms--A prospective mild traumatic brain injury (mTBI) cohort study.

PubMed

Oldenburg, Christian; Lundin, Anders; Edman, Gunnar; Nygren-de Boussard, Catharina; Bartfai, Aniko

2016-01-01

Having three or more persisting (i.e. > 3 months) post-concussion symptoms (PCS) affects a significant number of patients after a mild traumatic brain injury (mTBI). A common complaint is cognitive deficits. However, several meta-analyses have found no evidence of long-term cognitive impairment in mTBI patients. The study sought to answer two questions: first, is there a difference in cognitive performance between PCS and recovered mTBI patients? Second, is lower cognitive reserve a risk factor for developing PCS? Prospective inception cohort study. One hundred and twenty-two adult patients were recruited from emergency departments within 24 hours of an mTBI. Three months post-injury, participants completed the Rivermead Post Concussion Symptoms Questionnaire and a neuropsychological assessment. A healthy control group (n = 35) were recruited. The estimate of cognitive reserve was based upon sub-test Information from Wechsler Adult Intelligence Scale and international classifications of educational level and occupational skill level. mTBI patients showed reduced memory performance. Patients with lower cognitive reserve were 4.14-times more likely to suffer from PCS. mTBI may be linked to subtle executive memory deficits. Lower cognitive reserve appears to be a risk factor for PCS and indicates individual vulnerabilities.

Race/Ethnicity and Retention in Traumatic Brain Injury Outcomes Research: A Traumatic Brain Injury Model Systems National Database Study.

PubMed

Sander, Angelle M; Lequerica, Anthony H; Ketchum, Jessica M; Hammond, Flora M; Gary, Kelli Williams; Pappadis, Monique R; Felix, Elizabeth R; Johnson-Greene, Douglas; Bushnik, Tamara

2018-05-31

To investigate the contribution of race/ethnicity to retention in traumatic brain injury (TBI) research at 1 to 2 years postinjury. Community. With dates of injury between October 1, 2002, and March 31, 2013, 5548 whites, 1347 blacks, and 790 Hispanics enrolled in the Traumatic Brain Injury Model Systems National Database. Retrospective database analysis. Retention, defined as completion of at least 1 question on the follow-up interview by the person with TBI or a proxy. Retention rates 1 to 2 years post-TBI were significantly lower for Hispanic (85.2%) than for white (91.8%) or black participants (90.5%) and depended significantly on history of problem drug or alcohol use. Other variables associated with low retention included older age, lower education, violent cause of injury, and discharge to an institution versus private residence. The findings emphasize the importance of investigating retention rates separately for blacks and Hispanics rather than combining them or grouping either with other races or ethnicities. The results also suggest the need for implementing procedures to increase retention of Hispanics in longitudinal TBI research.

SU-E-T-485: In Vivo Dosimetry with EBT3 Radiochromic Films for TBI Treatments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lozares, S; Gracia, M; Olasolo, J

2015-06-15

Purpose: Total body irradiation (TBI) is a technique that requires special equipment to control “in vivo” the dose to the patient because it is a complex technique performed in extraordinary conditions. There are several devices to perform this task (diodes, TLDs, ionization chambers, MOSFET). In this paper we study the possibility of performing these measurements with radiochromic films EBT3 properly calibrated. This method has been compared to the PTW diodes system for TBI. Methods: Once made the TC to the patients, we measured different thicknesses of the relevant areas of the body (head, neck, chest with or without arms, umbilicusmore » area, knees and ankles); for each of these thicknesses we measured dose rate (cGy / UM) in RW3 phantom, in TBI conditions, with ionization chamber in the center; in turn, the input diode and the output of each configuration is placed to assign dose to each set of diodes. Movie calibration is performed according to manufacturer’s recommendations but TBI conditions. The dose at the center of each thickness compared to a linear interpolation of the dose at the entrance and exit, resulting in an adequate approximation. Finally in each session for each patient put a piece of film (2×2 cm2) at the entrance and another at the exit in each area, obtaining these readings and interpolating the estimated center dose, as with the diodes. Results: These results show a greater homogeneity in the distribution for use with film and validate the use of the same for this task and, if necessary, to avoid purchasing diode group if they have not. Conclusion: By using radiochromic films for this technique gives us a proper calculation of the dose received by the patient in the absence of other methods, or gives us a second additional track that already used normally.« less

Persistent hypogonadism influences estradiol synthesis, cognition and outcome in males after severe TBI.

PubMed

Wagner, Amy K; Brett, Christopher A; McCullough, Emily H; Niyonkuru, Christian; Loucks, Tammy L; Dixon, C Edward; Ricker, Joseph; Arenth, Patricia; Berga, Sarah L

2012-01-01

Acute hypogonadotropic hypogonadism (AHH) occurs frequently after TBI, as does chronic hypogonadotropic hypogonadism. However, AHH and persistent hypogonadotropic hypogonadism (PHH) after TBI are not well studied. The objective of this study was to characterize longitudinal hormone profiles and the impact of AHH and PHH on outcome. In this prospective cohort study, men with severe TBI (n = 38) had serum gonadal and gonadotropic hormones measured during weeks 1-52 post-injury. AHH, PHH and/or early resolving hypogonadotropic hypogonadism (ERHH) were based on temporal hormone assessments. PHH and hormone profiles were then compared to multiple outcome measures 6-12 months post-TBI. AHH affected 100% of the population, while 37% subsequently developed PHH. Acute testosterone (TEST) and estradiol/testosterone (E2/TEST) ratios were associated with PHH and outcome. Over time, post-acute TEST and E2 levels for the ERHH group approached normal range, while levels for the PHH group remained low. Post-acute gonadotrophin levels were within the normal range for both groups. PHH, along with lower post-acute TEST and E2 profiles, was associated with worse functional and cognitive outcomes at 6 and 12 months post-injury. These results support screening for post-acute secondary hypogonadism and further research to assess the mechanisms underlying PHH and associated functional and cognitive deficits.

Backscatter Correction Algorithm for TBI Treatment Conditions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sanchez-Nieto, B.; Sanchez-Doblado, F.; Arrans, R.

2015-01-15

The accuracy requirements in target dose delivery is, according to ICRU, ±5%. This is so not only in standard radiotherapy but also in total body irradiation (TBI). Physical dosimetry plays an important role in achieving this recommended level. The semi-infinite phantoms, customarily used for dosimetry purposes, give scatter conditions different to those of the finite thickness of the patient. So dose calculated in patient’s points close to beam exit surface may be overestimated. It is then necessary to quantify the backscatter factor in order to decrease the uncertainty in this dose calculation. The backward scatter has been well studied atmore » standard distances. The present work intends to evaluate the backscatter phenomenon under our particular TBI treatment conditions. As a consequence of this study, a semi-empirical expression has been derived to calculate (within 0.3% uncertainty) the backscatter factor. This factor depends lineally on the depth and exponentially on the underlying tissue. Differences found in the qualitative behavior with respect to standard distances are due to scatter in the bunker wall close to the measurement point.« less

Challenges and opportunities for pediatric severe TBI-review of the evidence and exploring a way forward.

PubMed

Bell, Michael J; Adelson, P David; Wisniewski, Stephen R

2017-10-01

Traumatic brain injury (TBI) is a leading killer of children in the developed and developing world. Despite evidence-based guidelines and several recent clinical trials, the progress in developing best practices for children with severe TBI has been slow. This article describes (i) the burden of the disease, (ii) the inadequacies of the evidence-based guidelines, (iii) the failure of the largest clinical trials to prove their primary hypotheses, and (iv) possible advances from an observational cohort study called the Approaches and Decisions for Acute Pediatric TBI (ADAPT) Trial that has recently completed enrollment.

Targeting Epigenetic Mechanisms in Pain due to Trauma and Traumatic Brain Injury(TBI)

DTIC Science & Technology

2016-10-01

particularly likely to involve TBI, peripheral trauma or both. Disability due to pain and other causes is very high amongst such patients. We have no...Chemokine, Disability , Analgesia, Spinal Cord 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT UU 18. NUMBER OF PAGES 15 19a. NAME OF...are particularly likely to involve TBI, peripheral trauma or both. Disability due to pain and other causes is very high amongst such patients. We have

Reintegrating Troops with Mild Traumatic Brain Injury (mTBI) into their Communities: Understanding the Scope and Timeline of Post-Deployment Driving Problems

DTIC Science & Technology

2015-10-01

behaviors and anxieties among post- deployed SMs with and without traumatic brain injury (TBI), post-traumatic stress syndrome (PTSD) or TBI with...post- traumatic stress syndrome (TBI/PTSD). The goal was to compare SMs who were post-deployment to SMs who had not served in OEF/OIF/OND, however all...in situations when SM would typically drive (p=.02) with TBI/PTSD reporting this more common than TBI and 0Dx. • Move to middle of road or onto

Tribes and tribulations: interdisciplinary eHealth in providing services for people with a traumatic brain injury (TBI).

PubMed

Hines, M; Brunner, M; Poon, S; Lam, M; Tran, V; Yu, D; Togher, L; Shaw, T; Power, E

2017-11-21

eHealth has potential for supporting interdisciplinary care in contemporary traumatic brain injury (TBI) rehabilitation practice, yet little is known about whether this potential is being realised, or what needs to be done to further support its implementation. The purpose of this study was to explore health professionals' experiences of, and attitudes towards eHealth technologies to support interdisciplinary practice within rehabilitation for people after TBI. A qualitative study using narrative analysis was conducted. One individual interview and three focus groups were conducted with health professionals (n = 17) working in TBI rehabilitation in public and private healthcare settings across regional and metropolitan New South Wales, Australia. Narrative analysis revealed that participants held largely favourable views about eHealth and its potential to support interdisciplinary practice in TBI rehabilitation. However, participants encountered various issues related to (a) the design of, and access to electronic medical records, (b) technology, (c) eHealth implementation, and (d) information and communication technology processes that disconnected them from the work they needed to accomplish. In response, health professionals attempted to make the most of unsatisfactory eHealth systems and processes, but were still mostly unsuccessful in optimising the quality, efficiency, and client-centredness of their work. Attention to sources of disconnection experienced by health professionals, specifically design of, and access to electronic health records, eHealth resourcing, and policies and procedures related to eHealth and interdisciplinary practice are required if the potential of eHealth for supporting interdisciplinary practice is to be realised.

The relationship between neurobehavioural problems of severe traumatic brain injury (TBI), family functioning and the psychological well-being of the spouse/caregiver: path model analysis.

PubMed

Anderson, Malcolm I; Parmenter, Trevor R; Mok, Magdalena

2002-09-01

This study used a modern theory of stress as a framework to strengthen the understanding of the relationship between neurobehavioural problems of TBI, family functioning and psychological distress in spouse/caregivers. The research was an ex post facto design utilising a cross-sectional methodology. Path analysis was used to determine the structural effect of neurobehavioural problems on family functioning and psychological distress. Forty-seven female and 17 male spouse/caregivers of partners with severe TBI were recruited. Spouse/caregivers who reported partners with TBI as having high levels of behavioural and cognitive problems experienced high levels of unhealthy family functioning. High levels of unhealthy family functioning were related to high levels of distress in spouse/caregivers, as family functioning had a moderate influence on psychological distress. Furthermore, indirect effects of behavioural and cognitive problems operating through family functioning intensified the level of psychological distress experienced by spouse/caregivers. Additionally, spouse/caregivers who reported high levels of behavioural, communication and social problems in their partners also experienced high levels of psychological distress. This study was significant because the impact of TBI on the spouse/caregiver from a multidimensional perspective is an important and under-researched area in the brain injury and disability field.

Deficits in comprehension of speech acts after TBI: The role of theory of mind and executive function.

PubMed

Honan, Cynthia A; McDonald, Skye; Gowland, Alison; Fisher, Alana; Randall, Rebekah K

2015-11-01

Theory of mind (ToM) is critical to effective communication following traumatic brain injury (TBI) however, whether impairments are specific to social cognition, or reflective of executive demands is unclear. This study examined whether ToM impairments are predicted by executive function difficulties using everyday conversation tasks. Twenty-five individuals with severe-TBI were compared to 25 healthy controls on low- and high-ToM tasks across four conditions: (1) low cognitive load, (2) high flexibility, (3) high working memory (WM) and (4) high inhibition. TBI individuals were impaired on high-ToM tasks in the WM condition. When the WM demands of the task were controlled, the impairments were no longer apparent. TBI individuals were not impaired on high-ToM tasks in the inhibition and flexibility conditions, suggesting these tasks may not have been sufficiently demanding of ToM abilities. The results suggest that ToM impairments in everyday communication may arise due to WM demands, in individuals with TBI. Copyright © 2015 Elsevier Inc. All rights reserved.

Exploring cognitive support use and preference by college students with TBI: A mixed-methods study.

PubMed

Brown, Jessica; Hux, Karen; Hey, Morgan; Murphy, Madeline

2017-01-01

Many college students with TBI rely on external strategies and supports to compensate for persistent memory, organization, and planning deficits that interfere with recalling and executing daily tasks. Practitioners know little, however, about the supports students with TBI choose for this purpose, the reasoning behind their choice, or preferred features of selected supports. The purpose of this study was to explore these issues. We collected and analyzed quantitative and qualitative data from eight college students with TBI for completion of a concurrent triangulation mixed-methods design. Data analysis included evaluation and triangulation of participant demographic information, survey responses about persistent post-injury symptoms, transcripts from semi-structured interviews about cognitive support devices and strategies, and ranking results about specific compensatory tools. Results suggest that college students with TBI prefer high-tech external supports-sometimes with the addition of low-tech, paper supports-to assist them in managing daily tasks. This preference related to features of portability, accessibility, and automatic reminders. An electronic calendar was the most-preferred high-tech support, and a paper checklist was the most-preferred low-tech support. Rehabilitation professionals should consider implementing high-tech supports with preferred characteristics during treatment given the preferences of students with TBI and the consequent likelihood of their continued long-term use following reintegration to community settings.

Usability evaluation of the SMART application for youth with mTBI.

PubMed

Dexheimer, Judith W; Kurowski, Brad G; Anders, Shilo H; McClanahan, Nicole; Wade, Shari L; Babcock, Lynn

2017-01-01

There is a dearth of evidence-based treatments available to address the significant morbidity associated with mild traumatic brain injury (mTBI). To address this gap, we designed a novel user-friendly, web-based application. We describe the preliminary evaluation of feasibility and usability of the application to promote recovery following mTBI in youth, the Self-Monitoring Activity-Restriction and Relaxation Treatment (SMART). SMART incorporates real-time recommendations for individualized symptom management and activity restriction along with training in cognitive-behavioral coping strategies. We conducted a usability evaluation to assess and modify the SMART system prior to further study and deployment. Children ages 11-18 years presenting to the emergency department were recruited after symptoms resolved. Usability was assessed using a 60-min think-aloud protocol of teens and parents describing their interaction with the application. Upon completion of the tasks, each participant also completed the system usability scale (SUS). We performed tests with 4 parent/child dyads. The average age of the children was 13 years (standard deviation=1.8). The parents were an average of 41.5 years old (standard deviation=6.2). Research revealed that the participants were enthusiastic about the interactive portions of the tool particularly the video based sessions. Parents were concerned about the speed at which their child might move through the program and the children thought that the system required large amounts of reading. Based on user feedback, researchers modified SMART to include an audio file in every module and improved the system's aesthetic properties. The mean SUS score was 85, with high SUS scores (>68) indicating satisfactory usability. High initial usability and favorable user feedback provide a foundation for further iterative development and testing of the SMART application as a tool for managing recovery from concussion. Copyright © 2016 Elsevier

Prevalence of suicidal behaviour following traumatic brain injury: Longitudinal follow-up data from the NIDRR Traumatic Brain Injury Model Systems.

PubMed

Fisher, Lauren B; Pedrelli, Paola; Iverson, Grant L; Bergquist, Thomas F; Bombardier, Charles H; Hammond, Flora M; Hart, Tessa; Ketchum, Jessica M; Giacino, Joseph; Zafonte, Ross

2016-01-01

This study utilized the Traumatic Brain Injury Model Systems (TBIMS) National Database to examine the prevalence of depression and suicidal behaviour in a large cohort of patients who sustained moderate-to-severe TBI. Participants presented to a TBIMS acute care hospital within 72 hours of injury and received acute care and comprehensive rehabilitation in a TBIMS designated brain injury inpatient rehabilitation programme. Depression and suicidal ideation were measured with the Patient Health Questionnaire (PHQ-9). Self-reported suicide attempts during the past year were recorded at each follow-up examination, at 1, 2, 3, 10, 15 and 20 years post-injury. Throughout the 20 years of follow-up, rates of depression ranged from 24.8-28.1%, suicidal ideation ranged from 7.0-10.1% and suicide attempts (past year) ranged from 0.8-1.7%. Participants who endorsed depression and/or suicidal behaviour at year 1 demonstrated consistently elevated rates of depression and suicidal behaviour 5 years after TBI. Compared to the general population, individuals with TBI are at greater risk for depression and suicidal behaviour many years after TBI. The significant psychiatric symptoms evidenced by individuals with TBI highlight the need for routine screening and mental health treatment in this population.

Impact of extended monitoring-guided intensive care on outcome after severe traumatic brain injury: A prospective multicentre cohort study (PariS-TBI study).

PubMed

Mateo, Joaquim; Payen, Didier; Ghout, Idir; Vallée, Fabrice; Lescot, Thomas; Welschbillig, Stephane; Tazarourte, Karim; Azouvi, Philippe; Weiss, Jean-Jacques; Aegerter, Philippe; Vigué, Bernard

2017-01-01

We evaluated whether an integrated monitoring with systemic and specific monitoring affect mortality and disability in adults with severe traumatic brain injury (sTBI). Adults with severeTBI (Glasgow Coma Scale [GCS] ≤ 8) admitted alive in intensive care units (ICUs) were prospectively included. Primary endpoints were in-hospital 30-day mortality and extended Glasgow outcome score (GOSE) at 3 years. Association with the intensity of monitoring and outcome was studied by comparing a high level of monitoring (HLM) (systemic and ≥3 specific monitoring) and low level of monitoring (LLM) (systemic and 0-2 specific monitoring) and using inverse probability weighting procedure. 476 patients were included and IPW was used to improve the balance between the two groups of treatments (HLM/LMM). Overall hospital mortality (at 30 days) was 43%, being significantly lower in HLM than LLM group (27% vs. 53%: RR, 1.63: 95% CI: 1.23-2.15). The 14-day hospital mortality was also lower in the HLM group than expected, based upon the CRASH prediction model (35%). At 3 years, disability was not significantly different between the monitoring groups. After adjustment, HLM group improved short-term mortality but did not show any improvement in the 3-year outcome compared with LLM.

Mission Connect Mild TBI Translational Research Consortium

DTIC Science & Technology

2013-08-01

acute neurological evaluations which are necessary to validate criteria for mTBI, rats are anesthetized with isoflurane and concussed with Vander...National Football League, Neurosurgery 61:223– 225, 2007 Dixon CE, Lyeth BG, Povlishock JT, Findling RL, Hamm RJ, Marmarou A, Young HF, and Hayes RL...Minster, R. L., Kamboh, M. I., Shakir, A. M., & Wecht, C. H. (2006). Chronic traumatic encephalopathy in a national football league player: Part II

Working memory capacity links cognitive reserve with long-term memory in moderate to severe TBI: a translational approach.

PubMed

Sandry, Joshua; DeLuca, John; Chiaravalloti, Nancy

2015-01-01

Traumatic brain injury (TBI) can have devastating negative consequences on an individuals' ability to remember information; however, there is variability among memory impairment resulting from TBI. Some individuals exhibit long-term memory (LTM) impairment while others do not. This variability has been explained, at least in part, by the theory of cognitive reserve (CR). The theory suggests that individuals who have spent significant time engaged in intellectually enriching activities (higher CR) are better able to withstand LTM impairment despite neurological injury. The cognitive mechanisms that underlie this relationship are not well-specified. Recent evidence suggests that working memory (WM) capacity may be one mediating variable that can help explain how/why cognitive reserve (CR) protects against LTM impairment. The present research tested this hypothesis in a sample of fifty moderate to severe TBI patients. Specific neuropsychological tests were administered to estimate CR, LTM and WM. The results were congruent with a recent theoretical model that implicates WM capacity as a mediating variable in the relationship between CR and LTM (Sobel's Z = 2.62, p = 0.009). These data corroborate recent findings in an alternate neurological population and suggest that WM is an underlying mechanism of CR. Additional research is necessary to establish whether (1) WM is an important individual difference variable to include in memory rehabilitation trials and (2) to determine whether rehabilitation and treatment strategies that specifically target WM may also lead to complimentary improvements on diagnostic tests of delayed LTM in TBI and other memory impaired populations.

A Randomized Controlled Trial of the Group-Based Modified Story Memory Technique in TBI

DTIC Science & Technology

2017-10-01

AWARD NUMBER: W81XWH-16-1-0726 TITLE: A Randomized Controlled Trial of the Group -Based Modified Story Memory Technique in TBI PRINCIPAL...2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER A Randomized Controlled Trial of the Group -Based Modified Story Memory Technique in TBI 5b. GRANT...forthcoming, The current study addresses this need through a double blind, placebo- controlled , randomized clinical trial (RCT) of a group

An examination of the Wechsler Adult Intelligence Scales, Fourth Edition (WAIS-IV) in individuals with complicated mild, moderate and Severe traumatic brain injury (TBI).

PubMed

Carlozzi, Noelle E; Kirsch, Ned L; Kisala, Pamela A; Tulsky, David S

2015-01-01

This study examined the clinical utility of the Wechsler Adult Intelligence Scales-Fourth Edition (WAIS-IV) in individuals with complicated mild, moderate or severe TBI. One hundred individuals with TBI (n = 35 complicated mild or moderate TBI; n = 65 severe TBI) and 100 control participants matched on key demographic variables from the WAIS-IV normative dataset completed the WAIS-IV. Univariate analyses indicated that participants with severe TBI had poorer performance than matched controls on all index scores and subtests (except Matrix Reasoning). Individuals with complicated mild/moderate TBI performed more poorly than controls on the Working Memory Index (WMI), Processing Speed Index (PSI), and Full Scale IQ (FSIQ), and on four subtests: the two processing speed subtests (SS, CD), two working memory subtests (AR, LN), and a perceptual reasoning subtest (BD). Participants with severe TBI had significantly lower scores than the complicated mild/moderate TBI on PSI, and on three subtests: the two processing speed subtests (SS and CD), and the new visual puzzles test. Effect sizes for index and subtest scores were generally small-to-moderate for the group with complicated mild/moderate and moderate-to-large for the group with severe TBI. PSI also showed good sensitivity and specificity for classifying individuals with severe TBI versus controls. Findings provide support for the clinical utility of the WAIS-IV in individuals with complicated mild, moderate, and severe TBI.

Patterns of post-acute health care utilization after a severe traumatic brain injury: Results from the PariS-TBI cohort.

PubMed

Jourdan, Claire; Bayen, Eleonore; Darnoux, Emmanuelle; Ghout, Idir; Azerad, Sylvie; Ruet, Alexis; Vallat-Azouvi, Claire; Pradat-Diehl, Pascale; Aegerter, Philippe; Weiss, Jean-Jacques; Azouvi, Philippe

2015-01-01

To assess brain injury services utilization and their determinants using Andersen's model. Prospective follow-up of the PariS-TBI inception cohort. Out of 504 adults with severe traumatic brain injury (TBI), 245 survived and 147 received a 4-year outcome assessment (mean age 33 years, 80% men). Provision rates of medical, rehabilitation, social and re-entry services and their relations to patients' characteristics were assessed. Following acute care discharge, 78% of patients received physiotherapy, 61% speech/cognitive therapy, 50% occupational therapy, 41% psychological assistance, 63% specialized medical follow-up, 21% community re-entry assistance. Health-related need factors, in terms of TBI severity, were the main predictors of services. Provision of each therapy was significantly associated with corresponding speech, motor and psychological impairments. However, care provision did not depend on cognitive impairments and cognitive therapy was related to pre-disposing and geographical factors. Community re-entry assistance was provided to younger and more independent patients. These quantitative findings illustrate strengths and weaknesses of late brain injury care provision in urban France and highlight the need to improve treatment of cognitive impairments.

Examining Intrinsic Thalamic Resting State Networks Using Graph Theory Analysis : Implications for mTBI detection

DTIC Science & Technology

2012-08-01

disruptions in the resting state networks and neurocognitive pathologies such as schizophrenia, Alzheimer’s disease and attention deficit hyperactive ... deficits associated with TBI [8,9,10]. However, there is a growing body of evidence suggesting that TBI could induce thalamic injury, classically...Inventory (NBSI), Post Traumatic Stress Disorder (PCL-C) and the Automated Neuropsychological Assessment Metrics (ANAM). C. Data Acquisition and

Animal modelling of traumatic brain injury in preclinical drug development: where do we go from here?

PubMed Central

Marklund, Niklas; Hillered, Lars

2011-01-01

Traumatic brain injury (TBI) is the leading cause of death and disability in young adults. Survivors of TBI frequently suffer from long-term personality changes and deficits in cognitive and motor performance, urgently calling for novel pharmacological treatment options. To date, all clinical trials evaluating neuroprotective compounds have failed in demonstrating clinical efficacy in cohorts of severely injured TBI patients. The purpose of the present review is to describe the utility of animal models of TBI for preclinical evaluation of pharmacological compounds. No single animal model can adequately mimic all aspects of human TBI owing to the heterogeneity of clinical TBI. To successfully develop compounds for clinical TBI, a thorough evaluation in several TBI models and injury severities is crucial. Additionally, brain pharmacokinetics and the time window must be carefully evaluated. Although the search for a single-compound, ‘silver bullet’ therapy is ongoing, a combination of drugs targeting various aspects of neuroprotection, neuroinflammation and regeneration may be needed. In summary, finding drugs and prove clinical efficacy in TBI is a major challenge ahead for the research community and the drug industry. For a successful translation of basic science knowledge to the clinic to occur we believe that a further refinement of animal models and functional outcome methods is important. In the clinical setting, improved patient classification, more homogenous patient cohorts in clinical trials, standardized treatment strategies, improved central nervous system drug delivery systems and monitoring of target drug levels and drug effects is warranted. LINKED ARTICLES This article is part of a themed issue on Translational Neuropharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue-4 PMID:21175576

Systems Biology Approaches for Discovering Biomarkers for Traumatic Brain Injury

PubMed Central

Feala, Jacob D.; AbdulHameed, Mohamed Diwan M.; Yu, Chenggang; Dutta, Bhaskar; Yu, Xueping; Schmid, Kara; Dave, Jitendra; Tortella, Frank

2013-01-01

Abstract The rate of traumatic brain injury (TBI) in service members with wartime injuries has risen rapidly in recent years, and complex, variable links have emerged between TBI and long-term neurological disorders. The multifactorial nature of TBI secondary cellular response has confounded attempts to find cellular biomarkers for its diagnosis and prognosis or for guiding therapy for brain injury. One possibility is to apply emerging systems biology strategies to holistically probe and analyze the complex interweaving molecular pathways and networks that mediate the secondary cellular response through computational models that integrate these diverse data sets. Here, we review available systems biology strategies, databases, and tools. In addition, we describe opportunities for applying this methodology to existing TBI data sets to identify new biomarker candidates and gain insights about the underlying molecular mechanisms of TBI response. As an exemplar, we apply network and pathway analysis to a manually compiled list of 32 protein biomarker candidates from the literature, recover known TBI-related mechanisms, and generate hypothetical new biomarker candidates. PMID:23510232

Automated Comprehensive Evaluation of mTBI Visual Dysfunction

DTIC Science & Technology

2017-04-01

Discussion: The results show that all ANAM subcomponents, except for math processing, are reduced in the mTBI population compared to controls. In...0.002534553 Math  Processing  0.099382065 Match to Sample  0.004264635     Table 2. MACE  p‐value  Orientation ‐ Month  0.325052733 Orientation ‐ Date

Influence of Mild Traumatic Brain Injury (TBI) and Posttraumatic Stress Disorder (PTSD) on Pain Intensity Levels in OEF/OIF/OND Veterans.

PubMed

Stojanovic, Milan P; Fonda, Jennifer; Fortier, Catherine Brawn; Higgins, Diana M; Rudolph, James L; Milberg, William P; McGlinchey, Regina E

2016-11-01

Mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) are common among US veterans of Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND). We postulated that these injuries may modulate pain processing in these individuals and affect their subjective pain levels. Cross-sectional. 310 deployed service members of OEF/OIF/OND without a lifetime history of moderate or severe TBI were included in this study. All participants completed a comprehensive evaluation for Blast Exposure, mTBI, PTSD, and Pain Levels. The Boston Assessment of TBI-Lifetime Version (BAT-L) was used to assess blast exposure and potential brain injury during military service. The Clinician-Administered PTSD Scale (CAPS) characterized presence and severity of PTSD. The Visual Analog Scale (VAS) was used to assess pain intensity over the previous month before the interview, with higher scores indicative of worse pain. Statistical analysis was performed by ANOVA and results were adjusted for co-morbidities, clinical characteristics and demographic data. In comparison to control participants (veterans without mTBI or current PTSD), veterans with both current PTSD and mTBI reported the highest pain intensity levels, followed by veterans with PTSD only (P < 0.0001 and P = 0.0005, respectively). Pain levels in veterans with mTBI only were comparable to control participants. Comorbid PTSD and mTBI is associated with increased self-reported pain intensity. mTBI alone was not associated with increased pain. Published by Oxford University Press on behalf of the American Academy of Pain Medicine 2016. This work is written by US Government employees and is in the public domain in the US.

Concordance of common data elements for assessment of subjective cognitive complaints after mild-traumatic brain injury: a TRACK-TBI Pilot Study.

PubMed

Ngwenya, Laura B; Gardner, Raquel C; Yue, John K; Burke, John F; Ferguson, Adam R; Huang, Michael C; Winkler, Ethan A; Pirracchio, Romain; Satris, Gabriela G; Yuh, Esther L; Mukherjee, Pratik; Valadka, Alex B; Okonkwo, David O; Manley, Geoffrey T

2018-06-04

To determine characteristics and concordance of subjective cognitive complaints (SCCs) 6 months following mild-traumatic brain injury (mTBI) as assessed by two different TBI common data elements (CDEs). The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Pilot Study was a prospective observational study that utilized the NIH TBI CDEs, Version 1.0. We examined variables associated with SCC, performance on objective cognitive tests (Wechsler Adult Intelligence Scale, California Verbal Learning Test, and Trail Making Tests A and B), and agreement on self-report of SCCs as assessed by the acute concussion evaluation (ACE) versus the Rivermead Post Concussion Symptoms Questionnaire (RPQ). In total, 68% of 227 participants endorsed SCCs at 6 months. Factors associated with SCC included less education, psychiatric history, and being assaulted. Compared to participants without SCC, those with SCC defined by RPQ performed significantly worse on all cognitive tests. There was moderate agreement between the two measures of SCCs (kappa = 0.567 to 0.680). We show that the symptom questionnaires ACE and RPQ show good, but not excellent, agreement for SCCs in an mTBI study population. Our results support the retention of RPQ as a basic CDE for mTBI research. BSI-18: Brief Symptom Inventory; 18CDEs: common data elements; CT: computed tomography; CVLT: California Verbal Learning Test; ED: emergency department; GCS: Glasgow coma scale; LOC: loss of consciousnessm; TBI: mild-traumatic brain injury; PTA: post-traumatic amnesia; SCC: subjective cognitive complaints; TBI: traumatic brain injury; TRACK-TBI: Transforming Research and Clinical Knowledge in Traumatic Brain Injury; TMT: Trail Making Test; WAIS-PSI: Wechsler Adult Intelligence Scale, Fourth Edition, Processing Speed Index.

Electrophysiological assessments of cognition and sensory processing in TBI: applications for diagnosis, prognosis and rehabilitation.

PubMed

Folmer, Robert L; Billings, Curtis J; Diedesch-Rouse, Anna C; Gallun, Frederick J; Lew, Henry L

2011-10-01

Traumatic brain injuries are often associated with damage to sensory and cognitive processing pathways. Because evoked potentials (EPs) and event-related potentials (ERPs) are generated by neuronal activity, they are useful for assessing the integrity of neural processing capabilities in patients with traumatic brain injury (TBI). This review of somatosensory, auditory and visual ERPs in assessments of TBI patients is provided with the hope that it will be of interest to clinicians and researchers who conduct or interpret electrophysiological evaluations of this population. Because this article reviews ERP studies conducted in three different sensory modalities, involving patients with a wide range of TBI severity ratings and circumstances, it is difficult to provide a coherent summary of findings. However, some general trends emerge that give rise to the following observations and recommendations: 1) bilateral absence of somatosensory evoked potentials (SEPs) is often associated with poor clinical prognosis and outcome; 2) the presence of normal ERPs does not guarantee favorable outcome; 3) ERPs evoked by a variety of sensory stimuli should be used to evaluate TBI patients, especially those with severe injuries; 4) time since onset of injury should be taken into account when conducting ERP evaluations of TBI patients or interpreting results; 5) because sensory deficits (e.g., vision impairment or hearing loss) affect ERP results, tests of peripheral sensory integrity should be conducted in conjunction with ERP recordings; and 6) patients' state of consciousness, physical and cognitive abilities to respond and follow directions should be considered when conducting or interpreting ERP evaluations. Published by Elsevier B.V.

An Interactive Visualization Framework to Support Exploration and Analysis of TBI/PTSD Clinical Data

DTIC Science & Technology

2017-05-01

techniques to overcome some of the challenges and complexities of the data . Our approach uses a novel adaptive window-based frequency sequence mining ...AWARD NUMBER: W81XWH-15-2-0016 TITLE: An Interactive Visualization Framework to Support Exploration and Analysis of TBI/PTSD Clinical Data ...Analysis of TBI/PTSD Clinical Data 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-2-0016 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Dr. Jesus Caban 5d

Mission Connect Mild TBI Translational Research Consortium

DTIC Science & Technology

2009-08-01

modalities. We recruited to the project Margaret A. Parsley to carry out the Mild Traumatic Brain Injuries (MTBIs) under the supervision of Doug DeWitt...abstracts: Hulsebosch CE, Johnson KM, Dewitt DS, Dash PK, Grill R, Parsley MA, Unabia G, Rea H, Perez-Polo JR. Role of IL-1 and TNF receptor activation in...neurological deficits after TBI National Neurotrauma Society, 2010 Johnson KM, Dewitt DS, Dash PK, Grill R, Parsley MA, Unabia G, Rea H, Perez-Polo

13C-labelled microdialysis studies of cerebral metabolism in TBI patients☆

PubMed Central

Carpenter, Keri L.H.; Jalloh, Ibrahim; Gallagher, Clare N.; Grice, Peter; Howe, Duncan J.; Mason, Andrew; Timofeev, Ivan; Helmy, Adel; Murphy, Michael P.; Menon, David K.; Kirkpatrick, Peter J.; Carpenter, T. Adrian; Sutherland, Garnette R.; Pickard, John D.; Hutchinson, Peter J.

2014-01-01

Human brain chemistry is incompletely understood and better methodologies are needed. Traumatic brain injury (TBI) causes metabolic perturbations, one result of which includes increased brain lactate levels. Attention has largely focussed on glycolysis, whereby glucose is converted to pyruvate and lactate, and is proposed to act as an energy source by feeding into neurons’ tricarboxylic acid (TCA) cycle, generating ATP. Also reportedly upregulated by TBI is the pentose phosphate pathway (PPP) that does not generate ATP but produces various molecules that are putatively neuroprotective, antioxidant and reparative, in addition to lactate among the end products. We have developed a novel combination of 13C-labelled cerebral microdialysis both to deliver 13C-labelled substrates into brains of TBI patients and recover the 13C-labelled metabolites, with high-resolution 13C NMR analysis of the microdialysates. This methodology has enabled us to achieve the first direct demonstration in humans that the brain can utilise lactate via the TCA cycle. We are currently using this methodology to make the first direct comparison of glycolysis and the PPP in human brain. In this article, we consider the application of 13C-labelled cerebral microdialysis for studying brain energy metabolism in patients. We set this methodology within the context of metabolic pathways in the brain, and 13C research modalities addressing them. PMID:24361470

Sexual functioning 1 year after traumatic brain injury: findings from a prospective traumatic brain injury model systems collaborative study.

PubMed

Sander, Angelle M; Maestas, Kacey Little; Pappadis, Monique R; Sherer, Mark; Hammond, Flora M; Hanks, Robin

2012-08-01

To investigate the incidence and types of sexual difficulties in men and women with traumatic brain injury (TBI) 1 year after injury, as well as their comfort level in discussing problems with health care professionals. Prospective cohort study. Community. Persons with TBI (N=223; 165 men and 58 women) who had been treated at 1 of 6 participating TBI Model Systems inpatient rehabilitation units and were living in the community. None. Derogatis Interview for Sexual Functioning-self-report (DISF-SR); Global Sexual Satisfaction Index (GSSI); structured interview regarding changes in sexual functioning; and comfort level discussing sexuality with health care professionals. Women with TBI scored significantly below the normative sample for all subscales of the DISF-SR, including sexual cognition/fantasy, arousal, sexual behavior/experience, and orgasm. Men scored significantly below the normative sample on all scales except arousal. Women reported greater dysfunction than men for sexual cognition/fantasy and arousal. Twenty-nine percent of participants reported dissatisfaction with sexual functioning on the GSSI, with a greater percentage of men reporting dissatisfaction. Sixty-eight percent of participants indicated that they would spontaneously raise issues of sexual difficulties with health care professionals, while the remainder would either bring it up only if directly asked or would not discuss it at all. Sexual difficulties were present in a substantial portion of community-dwelling people with TBI at 1 year after injury. Educational interventions to increase awareness among people with TBI and rehabilitation professionals are warranted, as well as interventions to improve sexual functioning. Copyright © 2012 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Impaired cortical mitochondrial function following TBI precedes behavioral changes

PubMed Central

Watson, William D.; Buonora, John E.; Yarnell, Angela M.; Lucky, Jessica J.; D’Acchille, Michaela I.; McMullen, David C.; Boston, Andrew G.; Kuczmarski, Andrew V.; Kean, William S.; Verma, Ajay; Grunberg, Neil E.; Cole, Jeffrey T.

2014-01-01

Traumatic brain injury (TBI) pathophysiology can be attributed to either the immediate, primary physical injury, or the delayed, secondary injury which begins minutes to hours after the initial injury and can persist for several months or longer. Because these secondary cascades are delayed and last for a significant time period post-TBI, they are primary research targets for new therapeutics. To investigate changes in mitochondrial function after a brain injury, both the cortical impact site and ipsilateral hippocampus of adult male rats 7 and 17 days after a controlled cortical impact (CCI) injury were examined. State 3, state 4, and uncoupler-stimulated rates of oxygen consumption, respiratory control ratios (RCRs) were measured and membrane potential quantified, and all were significantly decreased in 7 day post-TBI cortical mitochondria. By contrast, hippocampal mitochondria at 7 days showed only non-significant decreases in rates of oxygen consumption and membrane potential. NADH oxidase activities measured in disrupted mitochondria were normal in both injured cortex and hippocampus at 7 days post-CCI. Respiratory and phosphorylation capacities at 17 days post-CCI were comparable to naïve animals for both cortical and hippocampus mitochondria. However, unlike oxidative phosphorylation, membrane potential of mitochondria in the cortical lining of the impact site did not recover at 17 days, suggesting that while diminished cortical membrane potential at 17 days does not adversely affect mitochondrial capacity to synthesize ATP, it may negatively impact other membrane potential-sensitive mitochondrial functions. Memory status, as assessed by a passive avoidance paradigm, was not significantly impaired until 17 days after injury. These results indicate pronounced disturbances in cortical mitochondrial function 7 days after CCI which precede the behavioral impairment observed at 17 days. PMID:24550822

Blue and Red Light-Evoked Pupil Responses in Photophobic Subjects with TBI.

PubMed

Yuhas, Phillip T; Shorter, Patrick D; McDaniel, Catherine E; Earley, Michael J; Hartwick, Andrew T E

2017-01-01

Photophobia is a common symptom in individuals suffering from traumatic brain injury (TBI). Recent evidence has implicated blue light-sensitive intrinsically photosensitive retinal ganglion cells (ipRGCs) in contributing to the neural circuitry mediating photophobia in migraine sufferers. The goal of this work is to test the hypothesis that ipRGC function is altered in TBI patients with photophobia by assessing pupillary responses to blue and red light. Twenty-four case participants (mean age 43.3; 58% female), with mild TBI and self-reported photophobia, and 12 control participants (mean age 42.6; 58% female) were in this study. After 10 minutes of dark adaptation, blue (470 nm, 1 × 10 phots/s/cm) and red (625 nm, 7 × 10 phots/s/cm) flashing (0.1 Hz) light stimuli were delivered for 30 seconds to the dilated left eye while the right pupil was recorded. The amplitude of normalized pupil fluctuation (constriction and dilation) was quantified using Fourier fast transforms. In both case and control participants, the amplitude of pupil fluctuation was significantly less for the blue light stimuli as compared to the red light stimuli, consistent with a contribution of ipRGCs to these pupil responses. There was no significant difference in the mean pupil fluctuation amplitudes between the two participant groups, but case participants displayed greater variability in their pupil responses to the blue stimulus. Case and control participants showed robust ipRGC-mediated components in their pupil responses to blue light. The results did not support the hypothesis that ipRGCs are "hypersensitive" to light in TBI participants with photophobia. However, greater pupil response variability in the case subjects suggests that ipRGC function may be more heterogeneous in this group.

Investigation on using high-energy proton beam for total body irradiation (TBI).

PubMed

Zhang, Miao; Qin, Nan; Jia, Xun; Zou, Wei J; Khan, Atif; Yue, Ning J

2016-09-08

This work investigated the possibility of using proton beam for total body irradia-tion (TBI). We hypothesized the broad-slow-rising entrance dose from a monoen-ergetic proton beam can deliver a uniform dose to patient with varied thickness. Comparing to photon-based TBI, it would not require any patient-specific com-pensator or beam spoiler. The hypothesis was first tested by simulating 250 MeV, 275 MeV, and 300 MeV protons irradiating a wedge-shaped water phantom in a paired opposing arrangement using Monte Carlo (MC) method. To allow ± 7.5% dose variation, the maximum water equivalent thickness (WET) of a treatable patient separation was 29 cm for 250 MeV proton, and > 40 cm for 275 MeV and 300 MeV proton. The compared 6 MV photon can only treat patients with up to 15.5 cm water-equivalent separation. In the second step, we simulated the dose deposition from the same beams on a patient's whole-body CT scan. The maximum patient separation in WET was 23 cm. The calculated whole-body dose variations were ± 8.9%, ± 9.0%, ± 9.6%, and ± 14% for 250 MeV proton, 275 MeV proton, 300 MeV proton, and 6 MV photon. At last, we tested the current machine capability to deliver a monoenergetic proton beam with a large uniform field. Experiments were performed on a compact double scattering single-gantry proton system. With its C-shaped gantry design, the source-to-surface distance (SSD) reached 7 m. The measured dose deposition curve had 22 cm relatively flat entrance region. The full width half maximum field size was measured 105 cm. The current scatter filter had to be redesigned to produce a uniform intensity at such treatment distance. In con-clusion, this work demonstrated the possibility of using proton beam for TBI. The current commercially available proton machines would soon be ready for such task. © 2016 The Authors.

A systems biology strategy to identify molecular mechanisms of action and protein indicators of traumatic brain injury.

PubMed

Yu, Chenggang; Boutté, Angela; Yu, Xueping; Dutta, Bhaskar; Feala, Jacob D; Schmid, Kara; Dave, Jitendra; Tawa, Gregory J; Wallqvist, Anders; Reifman, Jaques

2015-02-01

The multifactorial nature of traumatic brain injury (TBI), especially the complex secondary tissue injury involving intertwined networks of molecular pathways that mediate cellular behavior, has confounded attempts to elucidate the pathology underlying the progression of TBI. Here, systems biology strategies are exploited to identify novel molecular mechanisms and protein indicators of brain injury. To this end, we performed a meta-analysis of four distinct high-throughput gene expression studies involving different animal models of TBI. By using canonical pathways and a large human protein-interaction network as a scaffold, we separately overlaid the gene expression data from each study to identify molecular signatures that were conserved across the different studies. At 24 hr after injury, the significantly activated molecular signatures were nonspecific to TBI, whereas the significantly suppressed molecular signatures were specific to the nervous system. In particular, we identified a suppressed subnetwork consisting of 58 highly interacting, coregulated proteins associated with synaptic function. We selected three proteins from this subnetwork, postsynaptic density protein 95, nitric oxide synthase 1, and disrupted in schizophrenia 1, and hypothesized that their abundance would be significantly reduced after TBI. In a penetrating ballistic-like brain injury rat model of severe TBI, Western blot analysis confirmed our hypothesis. In addition, our analysis recovered 12 previously identified protein biomarkers of TBI. The results suggest that systems biology may provide an efficient, high-yield approach to generate testable hypotheses that can be experimentally validated to identify novel mechanisms of action and molecular indicators of TBI. © 2014 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.

Accurate and dynamic predictive model for better prediction in medicine and healthcare.

PubMed

Alanazi, H O; Abdullah, A H; Qureshi, K N; Ismail, A S

2018-05-01

Information and communication technologies (ICTs) have changed the trend into new integrated operations and methods in all fields of life. The health sector has also adopted new technologies to improve the systems and provide better services to customers. Predictive models in health care are also influenced from new technologies to predict the different disease outcomes. However, still, existing predictive models have suffered from some limitations in terms of predictive outcomes performance. In order to improve predictive model performance, this paper proposed a predictive model by classifying the disease predictions into different categories. To achieve this model performance, this paper uses traumatic brain injury (TBI) datasets. TBI is one of the serious diseases worldwide and needs more attention due to its seriousness and serious impacts on human life. The proposed predictive model improves the predictive performance of TBI. The TBI data set is developed and approved by neurologists to set its features. The experiment results show that the proposed model has achieved significant results including accuracy, sensitivity, and specificity.

Enhanced Cognitive Rehabilitation to Treat Comorbid TBI and PTSD

DTIC Science & Technology

2016-10-01

therapeutic approaches and tests a modification of cognitive processing therapy (CPT), an empirically supported treatment for PTSD, in which CPT is...been organized into a manualized treatment, Cognitive Symptom Management and Rehabilitation Therapy (CogSMART), which teaches Veterans ways to...the Effects of Cognitive Processing Therapy on Psychological, Neuropsychological, and Speech Symptoms in Comorbid PTSD and TBI, Cognitive and

Life-bombing-injury-life: a qualitative follow-up study of Oklahoma City bombing survivors with TBI.

PubMed

Sample, Pat L; Greene, David; Johns, Nikole R

2012-01-01

To learn about and come to an understanding of the recovery process and outcomes experienced by the survivors of the 1995 Oklahoma City bombing, who sustained a traumatic brain injury (TBI) along with other injuries in the blast. A phenomenological study was conducted using in-person interviews, document and video-tape review, internet communication and researcher journals as the primary data set. A total of 20 of the 46 bombing survivors with TBI (44%) agreed to be a part of the study. The data collection process focused on stories about service needs, services accessed and long-term outcomes of the participants. The researchers' data analysis yielded four themes (Trauma-Healing-Support; What TBI?; How I went back to work and life; Now I really need assistance!) that represented the content and meanings of the interviews and supplemental data. A common thread running through the interviews of survivors with TBI was their portrayal of life-long medical, emotional, vocational and residential needs since the bombing. What they experienced in the months--extending into years--after the bombing was beyond their own anticipation and that of their families and healthcare professionals.

Chronic Stress and Fatigue-Related Quality of Life after Mild-to-Moderate Traumatic Brain Injury (TBI)

PubMed Central

Bay, Esther; de-Leon, Marita B.

2010-01-01

Objective To determine relationships between chronic stress, fatigue-related quality of life (QOL-F) and related covariates after mild-to-moderate traumatic brain injury (TBI). Design Observational and cross-sectional Participants A total of 84 community-dwelling individuals with mild-to-moderate TBI recruited from multiple out-patient rehabilitation clinics assessed on average 15 months after injury. Method Data were collected with self-report surveys and chart abstraction. Measures Neurofunctional Behavioral Inventory, Perceived Stress Scale-14, Impact of Events Scale, McGill Pain Short-form Scale, and modified version of the Fatigue Impact Scale. Results Fatigue-related quality of life was associated with somatic symptoms, perceived situational stress, but not with event-related stress (PTSD symptoms) related to index TBI, pre-injury demographic, or post-injury characteristics. Somatic symptoms and chronic situational stress accounted for 42% of the variance in QOL (F). Conclusions QOL (F) in community-dwelling individuals with mild-to- moderate TBI is associated with chronic situational stress and somatic symptoms. Symptom management strategies may need to include general stress management to reduce fatigue burden and improve quality of life. PMID:21169862

Neuro-, Trauma -, or Med/Surg-ICU: Does it matter where polytrauma patients with TBI are admitted? Secondary analysis of AAST-MITC decompressive craniectomy study

PubMed Central

Scalea, Tom; Sperry, Jason; Coimbra, Raul; Vercruysse, Gary; Jurkovich, Gregory J; Nirula, Ram

2016-01-01

Introduction Patients with non-traumatic acute intracranial pathology benefit from neurointensivist care. Similarly, trauma patients with and without TBI fare better when treated by a dedicated trauma team. No study has yet evaluated the role of specialized neurocritical (NICU) and trauma intensive care units (TICU) in the management of TBI patients, and it remains unclear which TBI patients are best served in NICU, TICU, or general (Med/Surg) ICU. Methods This study is a secondary analysis of The American Association for the Surgery of Trauma Multi-Institutional Trials Committee (AAST-MITC) decompressive craniectomy study. Twelve Level 1 trauma centers provided clinical data and head CT scans of patients with Glasgow Coma Scale (GCS) ≤13 and CT evidence of TBI. Non-ICU admissions were excluded. Multivariate logistic regression was performed to measure the association between ICU-type and survival and calculate the probability of death for increasing ISS. Polytrauma patients (ISS > 15) with TBI and isolated TBI patients (other AIS < 3) were analyzed separately. Results There were 3641 patients with CT evidence of TBI with 2951 admitted to an ICU. Prior to adjustment, patient demographics, injury severity, and survival differed significantly by unit type. After adjustment, unit-type, age and ISS remained independent predictors of death. Unit-type modified the effect of ISS on mortality. TBI-polytrauma patients admitted to a TICU had improved survival across increasing ISS (Fig1). Survival for isolated TBI patients was similar between TICU and NICU. Med/Surg ICU carried the greatest probability of death. Conclusion Polytrauma patients with TBI have lower mortality risk when admitted to a Trauma ICU. This survival benefit increases with increasing injury severity. Isolated TBI patients have similar mortality risk when admitted to a Neuro ICU compared to a Trauma ICU. Med/Surg ICU admission carries the highest mortality risk. PMID:28225527

Efficacy and acceptability of a home-based, family-inclusive intervention for veterans with TBI: A randomized controlled trial.

PubMed

Winter, Laraine; Moriarty, Helene J; Robinson, Keith; Piersol, Catherine V; Vause-Earland, Tracey; Newhart, Brian; Iacovone, Delores Blazer; Hodgson, Nancy; Gitlin, Laura N

2016-01-01

Traumatic brain injury (TBI) often undermines community re-integration, impairs functioning and produces other symptoms. This study tested an innovative programme for veterans with TBI, the Veterans' In-home Programme (VIP), delivered in veterans' homes, involving a family member and targeting the environment (social and physical) to promote community re-integration, mitigate difficulty with the most troubling TBI symptoms and facilitate daily functioning. Interviews and intervention sessions were conducted in homes or by telephone. Eighty-one veterans with TBI at a VA polytrauma programme and a key family member. This was a 2-group randomized controlled trial. Control-group participants received usual-care enhanced by two attention-control telephone calls. Follow-up interviews occurred up to 4 months after baseline interview. VIP's efficacy was evaluated using measures of community re-integration, target outcomes reflecting veterans' self-identified problems and self-rated functional competence. At follow-up, VIP participants had significantly higher community re-integration scores and less difficulty managing targeted outcomes, compared to controls. Self-rated functional competence did not differ between groups. In addition, VIP's acceptability was high. A home-based, family-inclusive service for veterans with TBI shows promise for improving meaningful outcomes and warrants further research and clinical application.

Effect of binasal occlusion (BNO) on the visual-evoked potential (VEP) in mild traumatic brain injury (mTBI).

PubMed

Ciuffreda, Kenneth J; Yadav, Naveen K; Ludlam, Diana P

2013-01-01

The purpose of the experiment was to assess the effect of binasal occlusion (BNO) on the visually-evoked potential (VEP) in visually-normal (VN) individuals and in those with mild traumatic brain injury (mTBI) for whom BNO frequently reduces their primary symptoms related to abnormally-increased visual motion sensitivity (VMS). Subjects were comprised of asymptomatic VN adults (n = 10) and individuals with mTBI (n = 10) having the symptom of VMS. Conventional full-field VEP testing was employed under two conditions: without BNO and with opaque BNO which blocked regions on either side of the VEP test stimulus. Subjective impressions were also assessed. In VN, the mean VEP amplitude decreased significantly with BNO in all subjects. In contrast, in mTBI, the mean VEP amplitude increased significantly with BNO in all subjects. Latency was normal and unaffected in all cases. Repeat VEP testing in three subjects from each group revealed similar test-re-test findings. Visuomotor activities improved, with reduced symptoms, with BNO in the mTBI group. It is speculated that individuals with mTBI habitually attempt to suppress visual information in the near retinal periphery to reduce their abnormal VMS, with addition of the BNO negating the suppressive influence and thus producing a widespread disinhibition effect and resultant increase in VEP amplitude.

Training in Goal-Oriented Attentional Self-Regulation Improves Executive Functioning in Veterans with Chronic TBI.

PubMed

Novakovic-Agopian, Tatjana; Kornblith, Erica S; Abrams, Gary; Burciaga-Rosales, Joaquin; Loya, Fred; D'Esposito, Mark; Chen, Anthony J-W

2018-05-02

Deficits in executive control functions are some of the most common and disabling consequences of both military and civilian brain injury. However, effective interventions are scant. The goal of this study was to assess whether cognitive rehabilitation training that was successfully applied in chronic civilian brain injury would be effective for military Veterans with TBI. In a prior study, participants with chronic acquired brain injury significantly improved after training in goal-oriented attentional self-regulation (GOALS) on measures of attention/executive function, functional task performance, and goal-directed control over neural processing on fMRI. The objective of this study was to assess effects of GOALS training in Veterans with chronic TBI. 33 Veterans with chronic TBI and executive difficulties in their daily life completed either five weeks of manualized Goal-Oriented Attentional Self-Regulation (GOALS) training or Brain-Health Education (BHE) matched in time and intensity. Evaluator-blinded assessments at baseline and post training included neuropsychological and complex functional task performance and self-report measures of emotional regulation. After GOALS, but not BHE training, participants significantly improved from baseline on primary outcome measures of: Overall Complex Attention/Executive Function composite neuropsychological performance score [F = 7.10, p =.01; partial 2 = .19], and on overall complex functional task performance (Goal Processing Scale Overall Performance) [F=6.92, p=.01, partial 2 =.20]. Additionally, post-GOALS participants indicated significant improvement on emotional regulation self-report measures [POMS Confusion Score F=6.05, p=.02, partial2=.20]. Training in attentional self-regulation applied to participant defined goals may improve cognitive functioning in Veterans with chronic TBI. Attention regulation training may not only impact executive control functioning in real world complex tasks, but may also

Dynamic association between perfusion and white matter integrity across time since injury in Veterans with history of TBI.

PubMed

Clark, Alexandra L; Bangen, Katherine J; Sorg, Scott F; Schiehser, Dawn M; Evangelista, Nicole D; McKenna, Benjamin; Liu, Thomas T; Delano-Wood, Lisa

2017-01-01

Cerebral blood flow (CBF) plays a critical role in the maintenance of neuronal integrity, and CBF alterations have been linked to deleterious white matter changes. Although both CBF and white matter microstructural alterations have been observed within the context of traumatic brain injury (TBI), the degree to which these pathological changes relate to one another and whether this association is altered by time since injury have not been examined. The current study therefore sought to clarify associations between resting CBF and white matter microstructure post-TBI. 37 veterans with history of mild or moderate TBI (mmTBI) underwent neuroimaging and completed health and psychiatric symptom questionnaires. Resting CBF was measured with multiphase pseudocontinuous arterial spin labeling (MPPCASL), and white matter microstructural integrity was measured with diffusion tensor imaging (DTI). The cingulate cortex and cingulum bundle were selected as a priori regions of interest for the ASL and DTI data, respectively, given the known vulnerability of these regions to TBI. Regression analyses controlling for age, sex, and posttraumatic stress disorder (PTSD) symptoms revealed a significant time since injury × resting CBF interaction for the left cingulum ( p  < 0.005). Decreased CBF was significantly associated with reduced cingulum fractional anisotropy (FA) in the chronic phase; however, no such association was observed for participants with less remote TBI. Our results showed that reduced CBF was associated with poorer white matter integrity in those who were further removed from their brain injury. Findings provide preliminary evidence of a possible dynamic association between CBF and white matter microstructure that warrants additional consideration within the context of the negative long-term clinical outcomes frequently observed in those with history of TBI. Additional cross-disciplinary studies integrating multiple imaging modalities (e.g., DTI, ASL) and

Impact of TBI on late effects in children treated by megatherapy for Stage IV neuroblastoma. A study of the French Society of Pediatric oncology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Flandin, Isabelle; Department of Radiotherapy/Oncology, Hospital Lyon Sud, Lyon; Hartmann, Olivier

2006-04-01

Purpose: To determine the contribution of total body irradiation (TBI) to late sequelae in children treated with high-dose chemotherapy and autologous bone marrow transplantation for Stage IV neuroblastoma. Patients and Methods: We compared two populations that were similar with regard to age, stage, pre-autologous bone marrow transplantation chemotherapy (CT) regimen, period of treatment, and follow-up (12 years). The TBI group (n = 32) received TBI as part of the megatherapy procedure (1982-1993), whereas the CT group (n 30) received conditioning without TBI (1985-1992). Analysis 12 years later focused on growth, weight and corpulence (body mass index) delay; hormonal deficiencies; liver,more » kidney, heart, ear, eye, and dental sequelae; school performance; and the incidence of secondary tumors. Results: Impact of TBI was most marked in relation to growth and weight delay, although the mean delay was not severe, probably because of treatment with growth hormones. Other consequences of TBI were thyroid insufficiency, cataracts, and a high incidence of secondary tumors. Hearing loss and dental agenesis were more prominent in the group treated with CT alone. No differences were observed in school performance. Conclusion: The most frequent side effects of TBI were cataracts, thyroid insufficiency, and growth delay, but more worrying is the risk of secondary tumors. Because of the young mean age of patients and the toxicity of TBI regimens without any survival advantage, regimens without TBI are preferable in the management of Stage IV neuroblastoma.« less

Patient Characterization Protocols for Psychophysiological Studies of Traumatic Brain Injury and Post-TBI Psychiatric Disorders

PubMed Central

Rapp, Paul E.; Rosenberg, Brenna M.; Keyser, David O.; Nathan, Dominic; Toruno, Kevin M.; Cellucci, Christopher J.; Albano, Alfonso M.; Wylie, Scott A.; Gibson, Douglas; Gilpin, Adele M. K.; Bashore, Theodore R.

2013-01-01

Psychophysiological investigations of traumatic brain injury (TBI) are being conducted for several reasons, including the objective of learning more about the underlying physiological mechanisms of the pathological processes that can be initiated by a head injury. Additional goals include the development of objective physiologically based measures that can be used to monitor the response to treatment and to identify minimally symptomatic individuals who are at risk of delayed-onset neuropsychiatric disorders following injury. Research programs studying TBI search for relationships between psychophysiological measures, particularly ERP (event-related potential) component properties (e.g., timing, amplitude, scalp distribution), and a participant’s clinical condition. Moreover, the complex relationships between brain injury and psychiatric disorders are receiving increased research attention, and ERP technologies are making contributions to this effort. This review has two objectives supporting such research efforts. The first is to review evidence indicating that TBI is a significant risk factor for post-injury neuropsychiatric disorders. The second objective is to introduce ERP researchers who are not familiar with neuropsychiatric assessment to the instruments that are available for characterizing TBI, post-concussion syndrome, and psychiatric disorders. Specific recommendations within this very large literature are made. We have proceeded on the assumption that, as is typically the case in an ERP laboratory, the investigators are not clinically qualified and that they will not have access to participant medical records. PMID:23885250

Animal models of traumatic brain injury

PubMed Central

Xiong, Ye; Mahmood, Asim; Chopp, Michael

2014-01-01

Traumatic brain injury (TBI) is a leading cause of mortality and morbidity in both civilian life and the battlefield worldwide. Survivors of TBI frequently experience long-term disabling changes in cognition, sensorimotor function and personality. Over the past three decades, animal models have been developed to replicate the various aspects of human TBI, to better understand the underlying pathophysiology and to explore potential treatments. Nevertheless, promising neuroprotective drugs, which were identified to be effective in animal TBI models, have all failed in phase II or phase III clinical trials. This failure in clinical translation of preclinical studies highlights a compelling need to revisit the current status of animal models of TBI and therapeutic strategies. PMID:23329160

Advancing Clinical Outcomes, Biomarkers and Treatments for Severe TBI

DTIC Science & Technology

2017-08-01

determining the neurobehavioral and neural effects of repetitive transcranial magnetic stimulation (rTMS), which is a non-invasive technique to stimulate the...examined to determine effectiveness in inducing structural and functional neural plasticity and improving neurobehavioral recovery after severe TBI...Specific Aims: Aim I will determine presence, direction and sustainability of rTMS-induced neurobehavioral effects measured with the Disability Rating

Employment Interventions for Return to Work in Working Aged Adults Following Traumatic Brain Injury (TBI): A Systematic Review. Campbell Systematic Reviews 2016:6

ERIC Educational Resources Information Center

Graham, Carolyn W.; West, Michael D.; Bourdon, Jessica L.; Inge, Katherine J.; Seward, Hannah E.

2016-01-01

Individuals with traumatic brain injury (TBI) often struggle to obtain competitive employment after sustaining a TBI, commonly as a result of the post-injury difficulties they exhibit (Andelic, Stevens, Sigurdardottir, Arango-Lasprilla, & Roe, 2009; Mansfield et al., 2015). The currently reported unemployment rate for people with TBI is…

Animal models of post-traumatic epilepsy.

PubMed

Ostergard, Thomas; Sweet, Jennifer; Kusyk, Dorian; Herring, Eric; Miller, Jonathan

2016-10-15

Post-traumatic epilepsy (PTE) is defined as the development of unprovoked seizures in a delayed fashion after traumatic brain injury (TBI). PTE lies at the intersection of two distinct fields of study, epilepsy and neurotrauma. TBI is associated with a myriad of both focal and diffuse anatomic injuries, and an ideal animal model of epilepsy after TBI must mimic the characteristics of human PTE. The three most commonly used models of TBI are lateral fluid percussion, controlled cortical injury, and weight drop. Much of what is known about PTE has resulted from use of these models. In this review, we describe the most commonly used animal models of TBI with special attention to their advantages and disadvantages with respect to their use as a model of PTE. Copyright © 2016 Elsevier B.V. All rights reserved.

Premorbid IQ Predicts Postconcussive Symptoms in OEF/OIF/OND Veterans with mTBI.

PubMed

Stewart-Willis, Jada J; Heyanka, Daniel; Proctor-Weber, Zoe; England, Heather; Bruhns, Maya

2018-03-01

Extant literature has demonstrated that symptoms of postconcussive syndrome (PCS) persist well beyond the expected 3-month post-injury recovery period in a minority of individuals with mild traumatic brain injury (mTBI). Suboptimal performance on validity measures and pre- and post-injury psychosocial stressors - rather than actual mTBI or current cognitive functioning - have been identified as predictors of chronic PCS. Whether premorbid IQ has any influence on chronic PCS has been understudied, in the context of established psychogenic etiologies. The sample included 31 veterans, who underwent mTBI neuropsychological evaluations six or more months post-injury in a VA outpatient neuropsychology clinic. A two-step multiple linear regression was conducted to examine the effects on the outcome variable, PCS (Neurobehavioral Symptom Inventory), of the following predictors: cognitive functioning (Repeatable Battery for the Assessment of Neuropsychological Status; Attention, Immediate Memory, and Delayed Memory Indices), performance validity, depression (Beck Depression Inventory-Second Edition), posttraumatic stress disorder (PTSD Checklist, Civilian Version), quality of sleep (Pittsburgh Sleep Quality Index), pain (Brief Pain Inventory), education, and Premorbid IQ (Wechsler Test of Adult Reading). The overall regression model containing all nine predictor variables was statistically significant. Depression (p < .05) and premorbid IQ (p < .05) were the most salient predictors of chronic PCS; in that lower premorbid IQ and greater endorsed symptoms of depression were associated with higher PCS scores. In Step 2 of the multiple linear regression, the WTAR explained an additional 6.7% of the variance in PCS after controlling for psychosocial stressors and current cognitive ability. The findings support premorbid IQ as a unique and relevant predictor of chronic PCS, with significance variance accounted for beyond education, cognitive functioning, and psychosocial

The experience of return to work in individuals with traumatic brain injury (TBI): A qualitative study.

PubMed

Libeson, Lauren; Downing, Marina; Ross, Pamela; Ponsford, Jennie

2018-05-10

Traumatic Brain Injury (TBI) is a leading cause of disability in young people, with return to work (RTW) a major goal of recovery. This qualitative study aimed to understand the RTW experience of individuals with TBI who received comprehensive vocational rehabilitation, and to identify facilitating and limiting factors in the RTW process. Semi-structured interviews were conducted with 15 individuals (mean age = 47.33 years) approximately 4.5 years post-injury, of whom 14 had moderate to severe TBI. Twelve individuals had successfully returned to work. Thematic analysis of transcribed interviews identified three key factors affecting RTW: client, work and rehabilitation factors. Across these factors, 12 themes reported to be critical to the success or failure of the RTW programme were identified. Client themes included social support, cognitive difficulties and motivation, with RTW too early associated with unfavourable outcomes. Work themes included work modifications, employer support and financial incentives. Rehabilitation themes included the RTW programme, the role of the vocational occupational therapist and work preparation. These key factors were reported to have impacted the RTW outcome, comprising three further themes: work satisfaction, future vocational outlook, and quality of life. Consideration of these factors can inform vocational rehabilitation programmes, potentially improving employment outcomes following TBI.

DTI measures identify mild and moderate TBI cases among patients with complex health problems: A receiver operating characteristic analysis of U.S. veterans.

PubMed

Main, Keith L; Soman, Salil; Pestilli, Franco; Furst, Ansgar; Noda, Art; Hernandez, Beatriz; Kong, Jennifer; Cheng, Jauhtai; Fairchild, Jennifer K; Taylor, Joy; Yesavage, Jerome; Wesson Ashford, J; Kraemer, Helena; Adamson, Maheen M

2017-01-01

Standard MRI methods are often inadequate for identifying mild traumatic brain injury (TBI). Advances in diffusion tensor imaging now provide potential biomarkers of TBI among white matter fascicles (tracts). However, it is still unclear which tracts are most pertinent to TBI diagnosis. This study ranked fiber tracts on their ability to discriminate patients with and without TBI. We acquired diffusion tensor imaging data from military veterans admitted to a polytrauma clinic (Overall n  = 109; Age: M  = 47.2, SD  = 11.3; Male: 88%; TBI: 67%). TBI diagnosis was based on self-report and neurological examination. Fiber tractography analysis produced 20 fiber tracts per patient. Each tract yielded four clinically relevant measures (fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity). We applied receiver operating characteristic (ROC) analyses to identify the most diagnostic tract for each measure. The analyses produced an optimal cutpoint for each tract. We then used kappa coefficients to rate the agreement of each cutpoint with the neurologist's diagnosis. The tract with the highest kappa was most diagnostic. As a check on the ROC results, we performed a stepwise logistic regression on each measure using all 20 tracts as predictors. We also bootstrapped the ROC analyses to compute the 95% confidence intervals for sensitivity, specificity, and the highest kappa coefficients. The ROC analyses identified two fiber tracts as most diagnostic of TBI: the left cingulum (LCG) and the left inferior fronto-occipital fasciculus (LIF). Like ROC, logistic regression identified LCG as most predictive for the FA measure but identified the right anterior thalamic tract (RAT) for the MD, RD, and AD measures. These findings are potentially relevant to the development of TBI biomarkers. Our methods also demonstrate how ROC analysis may be used to identify clinically relevant variables in the TBI population.

A model for traumatic brain injury using laser induced shockwaves

NASA Astrophysics Data System (ADS)

Selfridge, A.; Preece, D.; Gomez, V.; Shi, L. Z.; Berns, M. W.

2015-08-01

Traumatic brain injury (TBI) represents a major treatment challenge in both civilian and military medicine; on the cellular level, its mechanisms are poorly understood. As a method to study the dysfunctional repair mechanisms following injury, laser induced shock waves (LIS) are a useful way to create highly precise, well characterized mechanical forces. We present a simple model for TBI using laser induced shock waves as a model for damage. Our objective is to develop an understanding of the processes responsible for neuronal death, the ways in which we can manipulate these processes to improve cell survival and repair, and the importance of these processes at different levels of biological organization. The physics of shock wave creation has been modeled and can be used to calculate forces acting on individual neurons. By ensuring that the impulse is in the same regime as that occurring in practical TBI, the LIS model can ensure that in vitro conditions and damage are similar to those experienced in TBI. This model will allow for the study of the biochemical response of neurons to mechanical stresses, and can be combined with microfluidic systems for cell growth in order to better isolate areas of damage.

A preliminary model for posttraumatic brain injury depression.

PubMed

Malec, James F; Brown, Allen W; Moessner, Anne M; Stump, Timothy E; Monahan, Patrick

2010-07-01

To develop, based on previous research, and evaluate a model for depression after traumatic brain injury (TBI). Cross-sectional structural equation modeling (SEM) of data from consecutively recruited patients. Acute hospital and inpatient rehabilitation units. Adult patients (N=158) after hospital admission for moderate to severe TBI. Not applicable. External appraisal of ability in participants was measured by the Mayo-Portland Adaptability Inventory (MPAI-4) Ability Index completed by a TBI clinical nurse specialist. Patient self-appraisal of post-TBI ability and depression were measured by the Awareness Questionnaire and Beck Depression Inventory-II. Functional outcome 1 year after injury was assessed with the MPAI-4 Participation Index. Successive SEM resulted in a parsimonious model with excellent fit. Consistent with prior research, a moderately strong association between self-appraisal of post-TBI ability and depression was found. Injury severity, as measured by the duration of posttraumatic amnesia (PTA), was not significantly associated with post-TBI depression. The 1-year functional outcome was associated with depression and TBI severity. The strong association between self-appraisal of post-TBI ability and depression is consistent with the cognitive-behavioral model of depression and recommends consideration and further study of cognitive-behavioral therapy for post-TBI depression. The lack of association between TBI severity and depression may represent the indirect and proxy nature of current measures of TBI severity such as PTA. Emerging neuroimaging techniques (eg, diffusion tensor imaging, magnetic resonance imaging spectroscopy) may provide the more direct measures of disruption of brain function after TBI that are needed to advance this line of research. Copyright 2010 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Cerebral glucose uptake in patients with chronic mental and cognitive sequelae following a single blunt mild TBI without visible brain lesions.

PubMed

Komura, Akifumi; Kawasaki, Tomohiro; Yamada, Yuichi; Uzuyama, Shiho; Asano, Yoshitaka; Shinoda, Jun

2018-06-19

The aim of this study is to investigate glucose uptake on FDG-PET in patients with chronic mental and cognitive symptoms following a single blunt mild traumatic brain injury (TBI) and without visible brain lesions on CT/MRI. Eighty-nine consecutive patients (mean age 43.8±10.75) who had a single blunt mild TBI from a traffic accident and suffering from chronic mental and cognitive symptoms without visible brain lesions on CT/MRI were enrolled in the study. Patients underwent FDG-PET imaging, and the mean interval between the TBI and FDG-PET was 50.0 months. The Wechsler Adult Intelligence Scale version III testing was performed within one month of the FDG-PET. A control group consisting of 93 healthy adult volunteers (mean age 42.2±14.3 years) also underwent FDG-PET. The glucose uptake pattern from FDG-PET in the patient group was compared to that from normal controls using statistical parametric mapping. Glucose uptake was significantly decreased in the bilateral prefrontal area and significantly increased around the limbic system in the patient group compared to normal controls. This topographical pattern of glucose uptake is different from that reported previously in patients with diffuse axonal injury (DAI), but may be similar to that seen in patients with major depression disorder. These results suggest that the pathological mechanism causing chronic mental and cognitive symptoms in patients with a single blunt mild TBI and without visible brain lesions might be different from that due to primary axonopathy in patients with DAI.

An evaluation of the strategic approach to the rehabilitation of traumatic brain injury (TBI) patients

PubMed Central

Tomaszewski, Wiesław; Mańko, Grzegorz

2011-01-01

Summary Background The objective of our study was to evaluate a goal-driven strategic plan for the step-by-step rehabilitation of traumatic brain injury (TBI) patients, with effectiveness measured in terms of quality of life, as compared to patients treated according to a standard, progressive rehabilitation program. Material/Methods We studied 40 patients after TBI awakened from a long-term coma. The patients were divided into two equal groups: a control group (n=20) involving patients treated before the introduction of the strategic approach, and an experimental group (n=20) involving patients rehabilitated under the strategic approach. In evaluating the effectiveness of rehabilitation we used a structured interview with clinical observation and a scale for assessing the quality of life of patients after TBI. Results The deterioration in the quality of life of TBI patients is mainly related to difficulties in satisfying physiological needs, self-care, reduced mobility and disorders of cognitive, regulatory, and social functions. In both groups, the feature most susceptible to rehabilitation related change was movement, while the least susceptible functions were associated with the use of different means of transport. This change is significantly greater in persons in the experimental group, as compared to controls. Conclusions We found that a rehabilitation program controlled by a strategic plan, with the cooperation of the patient, is more effective in improving the quality of life, as the patient is more self-motivated to individually designed objectives. PMID:21873948

The Community Balance and Mobility Scale: A Pilot Study Detecting Impairments in Military Service Members With Comorbid Mild TBI and Psychological Health Conditions.

PubMed

Pape, Marcy M; Williams, Kathy; Kodosky, Paula N; Dretsch, Michael

2016-01-01

To compare the capacity of the Community Balance and Mobility Scale (CB&M) to identify balance and mobility deficits in Service Members (SMs) with mild traumatic brain injury and comorbid psychological health conditions (mTBI/PH) to other commonly used balance assessments. A clinical research institute that provides a 4-week, outpatient, interdisciplinary program for active-duty SMs with mTBI/PH. A nonrandomized, cross-sectional design that compared multiple measures between 2 groups-active duty SMs with (n = 8) and without (n = 8) the dual diagnosis of mTBI/PH. Gait speed, Activities-specific Balance Confidence scale (ABC), Functional Gait Assessment (FGA), and CB&M to assess functional balance among the community-dwelling, TBI population. Across all measures, the mTBI/PH group performed significantly worse (P ≤ .01) with the exception of the FGA. The abilities of all objective measures to distinguish participants with mTBI/PH from healthy controls ranged from fair to excellent (area under the curve [AUC] = 0.66-0.94). However, the CB&M showed the largest group differences in effect size (d = 2.6) and had the highest discriminate ability (AUC = 0.98; sensitivity 100%; specificity 88%). The CB&M appears to have higher sensitivity and specificity than other measures of balance in SMs with mTBI/PH. A higher cut score for the CB&M is needed for this population.

Physiological complexity of acute traumatic brain injury in patients treated with a brain oxygen protocol: utility of symbolic regression in predictive modeling of a dynamical system.

PubMed

Narotam, Pradeep K; Morrison, John F; Schmidt, Michael D; Nathoo, Narendra

2014-04-01

Predictive modeling of emergent behavior, inherent to complex physiological systems, requires the analysis of large complex clinical data streams currently being generated in the intensive care unit. Brain tissue oxygen protocols have yielded outcome benefits in traumatic brain injury (TBI), but the critical physiological thresholds for low brain oxygen have not been established for a dynamical patho-physiological system. High frequency, multi-modal clinical data sets from 29 patients with severe TBI who underwent multi-modality neuro-clinical care monitoring and treatment with a brain oxygen protocol were analyzed. The inter-relationship between acute physiological parameters was determined using symbolic regression (SR) as the computational framework. The mean patient age was 44.4±15 with a mean admission GCS of 6.6±3.9. Sixty-three percent sustained motor vehicle accidents and the most common pathology was intra-cerebral hemorrhage (50%). Hospital discharge mortality was 21%, poor outcome occurred in 24% of patients, and good outcome occurred in 56% of patients. Criticality for low brain oxygen was intracranial pressure (ICP) ≥22.8 mm Hg, for mortality at ICP≥37.1 mm Hg. The upper therapeutic threshold for cerebral perfusion pressure (CPP) was 75 mm Hg. Eubaric hyperoxia significantly impacted partial pressure of oxygen in brain tissue (PbtO2) at all ICP levels. Optimal brain temperature (Tbr) was 34-35°C, with an adverse effect when Tbr≥38°C. Survivors clustered at [Formula: see text] Hg vs. non-survivors [Formula: see text] 18 mm Hg. There were two mortality clusters for ICP: High ICP/low PbtO2 and low ICP/low PbtO2. Survivors maintained PbtO2 at all ranges of mean arterial pressure in contrast to non-survivors. The final SR equation for cerebral oxygenation is: [Formula: see text]. The SR-model of acute TBI advances new physiological thresholds or boundary conditions for acute TBI management: PbtO2≥25 mmHg; ICP≤22 mmHg; CPP≈60-75�

Quantitative Tractography and Volumetric MRI in Blast and Blunt Force TBI: Predictors of Neurocognitive and Behavioral Outcome

DTIC Science & Technology

2015-10-01

related psychosocial problems (e.g., fights, poor judgment, physical injuries, emotional problems) relative to the control group. Within mTBI, more... maps . Results showed that there were no significant differences in FA between the control and TBI groups across the 3 regions of interest; however...for PTSD symptoms; trends were also observed between lower PT FA, bodily pain, and greater fatigue. Lower FA of CST and ML-CTT was significantly

Defining the Pathophysiological Role of Tau in Experimental TBI

DTIC Science & Technology

2017-10-01

clinically a blood test for improving the diagnosis of TBI-induced chronic neurodegenerative disease in the long-term post -injury time period. The...we will complete the quantitative analysis of perforant pathway synapse integrity in all 63 long-term post -injury cases. Our results thus far support...substantiated by quantitative analysis of NeuN-positive neuronal density in lateral entorhinal cortex layer II at 4 months post -injury (Table 1). At

Diffusion tensor imaging (DTI) findings in adult civilian, military, and sport-related mild traumatic brain injury (mTBI): a systematic critical review.

PubMed

Asken, Breton Michael; DeKosky, Steven T; Clugston, James R; Jaffee, Michael S; Bauer, Russell M

2018-04-01

This review seeks to summarize diffusion tensor imaging (DTI) studies that have evaluated structural changes attributed to the mechanisms of mild traumatic brain injury (mTBI) in adult civilian, military, and athlete populations. Articles from 2002 to 2016 were retrieved from PubMed/MEDLINE, EBSCOhost, and Google Scholar, using a Boolean search string containing the following terms: "diffusion tensor imaging", "diffusion imaging", "DTI", "white matter", "concussion", "mild traumatic brain injury", "mTBI", "traumatic brain injury", and "TBI". We added studies not identified by this method that were found via manually-searched reference lists. We identified 86 eligible studies from English-language journals using, adult, human samples. Studies were evaluated based on duration between injury and DTI assessment, categorized as acute, subacute/chronic, remote mTBI, and repetitive brain trauma considerations. Since changes in brain structure after mTBI can also be affected by other co-occurring medical and demographic factors, we also briefly review DTI studies that have addressed socioeconomic status factors (SES), major depressive disorder (MDD), and attention-deficit hyperactivity disorder (ADHD). The review describes population-specific risks and the complications of clinical versus pathophysiological outcomes of mTBI. We had anticipated that the distinct population groups (civilian, military, and athlete) would require separate consideration, and various aspects of the study characteristics supported this. In general, study results suggested widespread but inconsistent differences in white matter diffusion metrics (primarily fractional anisotropy [FA], mean diffusivity [MD], radial diffusivity [RD], and axial diffusivity [AD]) following mTBI/concussion. Inspection of study designs and results revealed potential explanations for discrepant DTI findings, such as control group variability, analytic techniques, the manner in which regional differences were reported, and

Cone-beam CT of traumatic brain injury using statistical reconstruction with a post-artifact-correction noise model

NASA Astrophysics Data System (ADS)

Dang, H.; Stayman, J. W.; Sisniega, A.; Xu, J.; Zbijewski, W.; Yorkston, J.; Aygun, N.; Koliatsos, V.; Siewerdsen, J. H.

2015-03-01

Traumatic brain injury (TBI) is a major cause of death and disability. The current front-line imaging modality for TBI detection is CT, which reliably detects intracranial hemorrhage (fresh blood contrast 30-50 HU, size down to 1 mm) in non-contrast-enhanced exams. Compared to CT, flat-panel detector (FPD) cone-beam CT (CBCT) systems offer lower cost, greater portability, and smaller footprint suitable for point-of-care deployment. We are developing FPD-CBCT to facilitate TBI detection at the point-of-care such as in emergent, ambulance, sports, and military applications. However, current FPD-CBCT systems generally face challenges in low-contrast, soft-tissue imaging. Model-based reconstruction can improve image quality in soft-tissue imaging compared to conventional filtered back-projection (FBP) by leveraging high-fidelity forward model and sophisticated regularization. In FPD-CBCT TBI imaging, measurement noise characteristics undergo substantial change following artifact correction, resulting in non-negligible noise amplification. In this work, we extend the penalized weighted least-squares (PWLS) image reconstruction to include the two dominant artifact corrections (scatter and beam hardening) in FPD-CBCT TBI imaging by correctly modeling the variance change following each correction. Experiments were performed on a CBCT test-bench using an anthropomorphic phantom emulating intra-parenchymal hemorrhage in acute TBI, and the proposed method demonstrated an improvement in blood-brain contrast-to-noise ratio (CNR = 14.2) compared to FBP (CNR = 9.6) and PWLS using conventional weights (CNR = 11.6) at fixed spatial resolution (1 mm edge-spread width at the target contrast). The results support the hypothesis that FPD-CBCT can fulfill the image quality requirements for reliable TBI detection, using high-fidelity artifact correction and statistical reconstruction with accurate post-artifact-correction noise models.

Facial emotion recognition deficits following moderate-severe Traumatic Brain Injury (TBI): re-examining the valence effect and the role of emotion intensity.

PubMed

Rosenberg, Hannah; McDonald, Skye; Dethier, Marie; Kessels, Roy P C; Westbrook, R Frederick

2014-11-01

Many individuals who sustain moderate-severe traumatic brain injuries (TBI) are poor at recognizing emotional expressions, with a greater impairment in recognizing negative (e.g., fear, disgust, sadness, and anger) than positive emotions (e.g., happiness and surprise). It has been questioned whether this "valence effect" might be an artifact of the wide use of static facial emotion stimuli (usually full-blown expressions) which differ in difficulty rather than a real consequence of brain impairment. This study aimed to investigate the valence effect in TBI, while examining emotion recognition across different intensities (low, medium, and high). Twenty-seven individuals with TBI and 28 matched control participants were tested on the Emotion Recognition Task (ERT). The TBI group was more impaired in overall emotion recognition, and less accurate recognizing negative emotions. However, examining the performance across the different intensities indicated that this difference was driven by some emotions (e.g., happiness) being much easier to recognize than others (e.g., fear and surprise). Our findings indicate that individuals with TBI have an overall deficit in facial emotion recognition, and that both people with TBI and control participants found some emotions more difficult than others. These results suggest that conventional measures of facial affect recognition that do not examine variance in the difficulty of emotions may produce erroneous conclusions about differential impairment. They also cast doubt on the notion that dissociable neural pathways underlie the recognition of positive and negative emotions, which are differentially affected by TBI and potentially other neurological or psychiatric disorders.

A Novel Closed-Head Model of Mild Traumatic Brain Injury Using Focal Primary Overpressure Blast to the Cranium in Mice

PubMed Central

Guley, Natalie H.; Rogers, Joshua T.; Del Mar, Nobel A.; Deng, Yunping; Islam, Rafiqul M.; D'Surney, Lauren; Ferrell, Jessica; Deng, Bowei; Hines-Beard, Jessica; Bu, Wei; Ren, Huiling; Elberger, Andrea J.; Marchetta, Jeffrey G.; Rex, Tonia S.; Honig, Marcia G.

2016-01-01

Abstract Mild traumatic brain injury (TBI) from focal head impact is the most common form of TBI in humans. Animal models, however, typically use direct impact to the exposed dura or skull, or blast to the entire head. We present a detailed characterization of a novel overpressure blast system to create focal closed-head mild TBI in mice. A high-pressure air pulse limited to a 7.5 mm diameter area on the left side of the head overlying the forebrain is delivered to anesthetized mice. The mouse eyes and ears are shielded, and its head and body are cushioned to minimize movement. This approach creates mild TBI by a pressure wave that acts on the brain, with minimal accompanying head acceleration-deceleration. A single 20-psi blast yields no functional deficits or brain injury, while a single 25–40 psi blast yields only slight motor deficits and brain damage. By contrast, a single 50–60 psi blast produces significant visual, motor, and neuropsychiatric impairments and axonal damage and microglial activation in major fiber tracts, but no contusive brain injury. This model thus reproduces the widespread axonal injury and functional impairments characteristic of closed-head mild TBI, without the complications of systemic or ocular blast effects or head acceleration that typically occur in other blast or impact models of closed-skull mild TBI. Accordingly, our model provides a simple way to examine the biomechanics, pathophysiology, and functional deficits that result from TBI and can serve as a reliable platform for testing therapies that reduce brain pathology and deficits. PMID:26414413

Counselor-Assisted Problem Solving (CAPS) Improves Behavioral Outcomes in Older Adolescents with Complicated Mild to Severe TBI

PubMed Central

Wade, Shari L.; Stancin, Terry; Kirkwood, Michael; Brown, Tanya Maines; Rochester, Mayo Clinic; McMullen, Kendra M.; Taylor, H. Gerry

2013-01-01

Objective To test the efficacy of Counselor-Assisted Problem Solving (CAPS) versus an internet resources comparison (IRC) condition in reducing behavior problems in adolescents following traumatic brain injury (TBI). Design Randomized clinical trial with interviewers naïve to treatment condition. Setting Three large tertiary children's hospitals and two general hospitals with pediatric commitment. Participants 132 children ages 12-17 years hospitalized during the previous 6 months for moderate to severe TBI. Interventions Participants in CAPS (n = 65) completed 8-12 online modules providing training in problem solving, communication skills, and self-regulation and subsequent synchronous videoconferences with a therapist. Participants in the IRC group (n = 67) received links to internet resources about pediatric TBI. Main Outcome Measures Child Behavior Checklist (CBCL) administered before and after completion of treatment (i.e., approximately six months after treatment initiation). Results Post hoc analysis of covariance (ANCOVA), controlling for pre-treatment scores, was used to examine group differences in behavior problems in the entire sample and among older (n=59) and younger adolescents (n=53). Among older but not younger adolescents, CAPS resulted in greater improvements on multiple dimensions of externalizing behavior problems than did IRC. Conclusion Online problem-solving therapy may be effective in reducing behavior problems in older adolescent survivors of moderate-severe TBI. PMID:23640543

Vocational rehabilitation after traumatic brain injury: models and services.

PubMed

Tyerman, Andy

2012-01-01

A recent systematic review suggests that around 40% of people with traumatic brain injury (TBI) return to work (RTW). Yet in the U.K. currently only a small minority of people with TBI receive vocational rehabilitation (VR) to enable a RTW. Agencies with an interest in developing such services are likely to favour different models of VR. The primary objective of this paper was to review models of specialist VR after TBI and their outcomes to inform service development across relevant agencies. A literature review on VR after TBI was undertaken in MEDLINE, EMBASE and PsychINFO (from 1967 to date). Papers reporting models of VR were selected for more detailed consideration. Illustrative examples of VR models are outlined: brain injury rehabilitation programmes with added VR elements, VR models adapted for TBI, case coordination/resource facilitation models, and consumer-directed models. Models differ, both within and across these four broad categories, in provision of core TBI rehabilitation, work preparation, work trials and supported placements. Methodological variation limits direct comparison of outcomes across models with few comparative or controlled studies. There is evidence to support the benefits of a wide range of models of specialist VR after TBI. However, there remains a need for controlled studies to inform service development and more evidence on cost-effectiveness to inform funding decisions.

Effects of Low-Level Blast Exposure on the Nervous System: Is There Really a Controversy?

PubMed Central

Elder, Gregory A.; Stone, James R.; Ahlers, Stephen T.

2014-01-01

High-pressure blast waves can cause extensive CNS injury in human beings. However, in combat settings, such as Iraq and Afghanistan, lower level exposures associated with mild traumatic brain injury (mTBI) or subclinical exposure have been much more common. Yet controversy exists concerning what traits can be attributed to low-level blast, in large part due to the difficulty of distinguishing blast-related mTBI from post-traumatic stress disorder (PTSD). We describe how TBI is defined in human beings and the problems posed in using current definitions to recognize blast-related mTBI. We next consider the problem of applying definitions of human mTBI to animal models, in particular that TBI severity in human beings is defined in relation to alteration of consciousness at the time of injury, which typically cannot be assessed in animals. However, based on outcome assessments, a condition of “low-level” blast exposure can be defined in animals that likely approximates human mTBI or subclinical exposure. We review blast injury modeling in animals noting that inconsistencies in experimental approach have contributed to uncertainty over the effects of low-level blast. Yet, animal studies show that low-level blast pressure waves are transmitted to the brain. In brain, low-level blast exposures cause behavioral, biochemical, pathological, and physiological effects on the nervous system including the induction of PTSD-related behavioral traits in the absence of a psychological stressor. We review the relationship of blast exposure to chronic neurodegenerative diseases noting the paradoxical lowering of Abeta by blast, which along with other observations suggest that blast-related TBI is pathophysiologically distinct from non-blast TBI. Human neuroimaging studies show that blast-related mTBI is associated with a variety of chronic effects that are unlikely to be explained by co-morbid PTSD. We conclude that abundant evidence supports low-level blast as having long

Cognitive control of conscious error awareness: error awareness and error positivity (Pe) amplitude in moderate-to-severe traumatic brain injury (TBI)

PubMed Central

Logan, Dustin M.; Hill, Kyle R.; Larson, Michael J.

2015-01-01

Poor awareness has been linked to worse recovery and rehabilitation outcomes following moderate-to-severe traumatic brain injury (M/S TBI). The error positivity (Pe) component of the event-related potential (ERP) is linked to error awareness and cognitive control. Participants included 37 neurologically healthy controls and 24 individuals with M/S TBI who completed a brief neuropsychological battery and the error awareness task (EAT), a modified Stroop go/no-go task that elicits aware and unaware errors. Analyses compared between-group no-go accuracy (including accuracy between the first and second halves of the task to measure attention and fatigue), error awareness performance, and Pe amplitude by level of awareness. The M/S TBI group decreased in accuracy and maintained error awareness over time; control participants improved both accuracy and error awareness during the course of the task. Pe amplitude was larger for aware than unaware errors for both groups; however, consistent with previous research on the Pe and TBI, there were no significant between-group differences for Pe amplitudes. Findings suggest possible attention difficulties and low improvement of performance over time may influence specific aspects of error awareness in M/S TBI. PMID:26217212

Anything goes? Regulation of the neural processes underlying response inhibition in TBI patients.

PubMed

Moreno-López, Laura; Manktelow, Anne E; Sahakian, Barbara J; Menon, David K; Stamatakis, Emmanuel A

2017-02-01

Despite evidence for beneficial use of methylphenidate in response inhibition, no studies so far have investigated the effects of this drug in the neurobiology of inhibitory control in traumatic brain injury (TBI), even though impulsive behaviours are frequently reported in this patient group. We investigated the neural basis of response inhibition in a group of TBI patients using functional magnetic resonance imaging and a stop-signal paradigm. In a randomised double-blinded crossover study, the patients received either a single 30mg dose of methylphenidate or placebo and performed the stop-signal task. Activation in the right inferior frontal gyrus (RIFG), an area associated with response inhibition, was significantly lower in patients compared to healthy controls. Poor response inhibition in this group was associated with greater connectivity between the RIFG and a set of regions considered to be part of the default mode network (DMN), a finding that suggests the interplay between DMN and frontal executive networks maybe compromised. A single dose of methylphenidate rendered activity and connectivity profiles of the patients RIFG near normal. The results of this study indicate that the neural circuitry involved in response inhibition in TBI patients may be partially restored with methylphenidate. Given the known mechanisms of action of methylphenidate, the effect we observed may be due to increased dopamine and noradrenaline levels. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Neuroproteomics and Systems Biology Approach to Identify Temporal Biomarker Changes Post Experimental Traumatic Brain Injury in Rats.

PubMed

Kobeissy, Firas H; Guingab-Cagmat, Joy D; Zhang, Zhiqun; Moghieb, Ahmed; Glushakova, Olena Y; Mondello, Stefania; Boutté, Angela M; Anagli, John; Rubenstein, Richard; Bahmad, Hisham; Wagner, Amy K; Hayes, Ronald L; Wang, Kevin K W

2016-01-01

Traumatic brain injury (TBI) represents a critical health problem of which diagnosis, management, and treatment remain challenging. TBI is a contributing factor in approximately one-third of all injury-related deaths in the United States. The Centers for Disease Control and Prevention estimate that 1.7 million people suffer a TBI in the United States annually. Efforts continue to focus on elucidating the complex molecular mechanisms underlying TBI pathophysiology and defining sensitive and specific biomarkers that can aid in improving patient management and care. Recently, the area of neuroproteomics-systems biology is proving to be a prominent tool in biomarker discovery for central nervous system injury and other neurological diseases. In this work, we employed the controlled cortical impact (CCI) model of experimental TBI in rat model to assess the temporal-global proteome changes after acute (1 day) and for the first time, subacute (7 days), post-injury time frame using the established cation-anion exchange chromatography-1D SDS gel electrophoresis LC-MS/MS platform for protein separation combined with discrete systems biology analyses to identify temporal biomarker changes related to this rat TBI model. Rather than focusing on any one individual molecular entity, we used in silico systems biology approach to understand the global dynamics that govern proteins that are differentially altered post-injury. In addition, gene ontology analysis of the proteomic data was conducted in order to categorize the proteins by molecular function, biological process, and cellular localization. Results show alterations in several proteins related to inflammatory responses and oxidative stress in both acute (1 day) and subacute (7 days) periods post-TBI. Moreover, results suggest a differential upregulation of neuroprotective proteins at 7 days post-CCI involved in cellular functions such as neurite growth, regeneration, and axonal guidance. Our study is among the

Concussion As a Multi-Scale Complex System: An Interdisciplinary Synthesis of Current Knowledge

PubMed Central

Kenzie, Erin S.; Parks, Elle L.; Bigler, Erin D.; Lim, Miranda M.; Chesnutt, James C.; Wakeland, Wayne

2017-01-01

Traumatic brain injury (TBI) has been called “the most complicated disease of the most complex organ of the body” and is an increasingly high-profile public health issue. Many patients report long-term impairments following even “mild” injuries, but reliable criteria for diagnosis and prognosis are lacking. Every clinical trial for TBI treatment to date has failed to demonstrate reliable and safe improvement in outcomes, and the existing body of literature is insufficient to support the creation of a new classification system. Concussion, or mild TBI, is a highly heterogeneous phenomenon, and numerous factors interact dynamically to influence an individual’s recovery trajectory. Many of the obstacles faced in research and clinical practice related to TBI and concussion, including observed heterogeneity, arguably stem from the complexity of the condition itself. To improve understanding of this complexity, we review the current state of research through the lens provided by the interdisciplinary field of systems science, which has been increasingly applied to biomedical issues. The review was conducted iteratively, through multiple phases of literature review, expert interviews, and systems diagramming and represents the first phase in an effort to develop systems models of concussion. The primary focus of this work was to examine concepts and ways of thinking about concussion that currently impede research design and block advancements in care of TBI. Results are presented in the form of a multi-scale conceptual framework intended to synthesize knowledge across disciplines, improve research design, and provide a broader, multi-scale model for understanding concussion pathophysiology, classification, and treatment. PMID:29033888

Behavioral and pathophysiological outcomes associated with caffeine consumption and repetitive mild traumatic brain injury (RmTBI) in adolescent rats

PubMed Central

Yamakawa, Glenn R.; Lengkeek, Connor; Salberg, Sabrina; Spanswick, Simon C.; Mychasiuk, Richelle

2017-01-01

Given that caffeine consumption is exponentially rising in adolescents and they are at increased risk for repetitive mild traumatic brain injury (RmTBI), we sought to examine the pathophysiological outcomes associated with early life caffeine consumption and RmTBI. Adolescent male and female Sprague Dawley rats received either caffeine in the drinking water or normal water and were then randomly assigned to 3 mild injuries using our lateral impact device or 3 sham procedures. Following injury induction, behavioral outcomes were measured with a test battery designed to examine symptoms consistent with clinical manifestation of PCS (balance and motor coordination, anxiety, short-term working memory, and depressive-like behaviours). In addition, pathophysiological outcomes were examined with histological measures of volume and cellular proliferation in the dentate gyrus, as well as microglia activation in the ventromedial hypothalamus. Finally, modifications to expression of 12 genes (Adora2a, App, Aqp4, Bdnf, Bmal1, Clock, Cry, Gfap, Orx1, Orx2, Per, Tau), in the prefrontal cortex, hippocampus, and/or the hypothalamus were assessed. We found that chronic caffeine consumption in adolescence altered normal developmental trajectories, as well as recovery from RmTBI. Of particular importance, many of the outcomes exhibited sex-dependent responses whereby the sex of the animal modified response to caffeine, RmTBI, and the combination of the two. These results suggest that caffeine consumption in adolescents at high risk for RmTBI should be monitored. PMID:29108016

Behavioral and pathophysiological outcomes associated with caffeine consumption and repetitive mild traumatic brain injury (RmTBI) in adolescent rats.

PubMed

Yamakawa, Glenn R; Lengkeek, Connor; Salberg, Sabrina; Spanswick, Simon C; Mychasiuk, Richelle

2017-01-01

Given that caffeine consumption is exponentially rising in adolescents and they are at increased risk for repetitive mild traumatic brain injury (RmTBI), we sought to examine the pathophysiological outcomes associated with early life caffeine consumption and RmTBI. Adolescent male and female Sprague Dawley rats received either caffeine in the drinking water or normal water and were then randomly assigned to 3 mild injuries using our lateral impact device or 3 sham procedures. Following injury induction, behavioral outcomes were measured with a test battery designed to examine symptoms consistent with clinical manifestation of PCS (balance and motor coordination, anxiety, short-term working memory, and depressive-like behaviours). In addition, pathophysiological outcomes were examined with histological measures of volume and cellular proliferation in the dentate gyrus, as well as microglia activation in the ventromedial hypothalamus. Finally, modifications to expression of 12 genes (Adora2a, App, Aqp4, Bdnf, Bmal1, Clock, Cry, Gfap, Orx1, Orx2, Per, Tau), in the prefrontal cortex, hippocampus, and/or the hypothalamus were assessed. We found that chronic caffeine consumption in adolescence altered normal developmental trajectories, as well as recovery from RmTBI. Of particular importance, many of the outcomes exhibited sex-dependent responses whereby the sex of the animal modified response to caffeine, RmTBI, and the combination of the two. These results suggest that caffeine consumption in adolescents at high risk for RmTBI should be monitored.

Novel Treatment for Patients with Traumatic Brain Injury (TBI)

DTIC Science & Technology

2016-06-01

equieffectiv e dose of phenylephri ne (PE)? 18 Does AVP maintain brain and muscle tissue 02 during CPP managemen t after TBI relative to an... Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any...discuss the meeting dates. I can be reached by telephone or email as listed below. K nnet 1·0 t ,. ti .. P ofessor of Surgery Leonard M. Miller

rTMS: A Treatment to Restore Function After Severe TBI

DTIC Science & Technology

2016-10-01

of rTMS-induced neurobehavioral effects measured with the Disability Rating Scale. Aim II will determine the presence, direction and sustainability...Aim IV addresses the need to confirm rTMS safety for severe TBI. 15. SUBJECT TERMS Disability Rating Scale (DRS), Neurobehavioral, Repetitive...rTMS sessions. The Disability Rating Scale (DRS) will be used at four time points to measure neurobehavioral recovery slopes. Net neural effects

Predicting Long-Term Global Outcome after Traumatic Brain Injury: Development of a Practical Prognostic Tool Using the Traumatic Brain Injury Model Systems National Database.

PubMed

Walker, William C; Stromberg, Katharine A; Marwitz, Jennifer H; Sima, Adam P; Agyemang, Amma A; Graham, Kristin M; Harrison-Felix, Cynthia; Hoffman, Jeanne M; Brown, Allen W; Kreutzer, Jeffrey S; Merchant, Randall

2018-05-16

For patients surviving serious traumatic brain injury (TBI), families and other stakeholders often desire information on long-term functional prognosis, but accurate and easy-to-use clinical tools are lacking. We aimed to build utilitarian decision trees from commonly collected clinical variables to predict Glasgow Outcome Scale (GOS) functional levels at 1, 2, and 5 years after moderate-to-severe closed TBI. Flexible classification tree statistical modeling was used on prospectively collected data from the TBI-Model Systems (TBIMS) inception cohort study. Enrollments occurred at 17 designated, or previously designated, TBIMS inpatient rehabilitation facilities. Analysis included all participants with nonpenetrating TBI injured between January 1997 and January 2017. Sample sizes were 10,125 (year-1), 8,821 (year-2), and 6,165 (year-5) after cross-sectional exclusions (death, vegetative state, insufficient post-injury time, and unavailable outcome). In our final models, post-traumatic amnesia (PTA) duration consistently dominated branching hierarchy and was the lone injury characteristic significantly contributing to GOS predictability. Lower-order variables that added predictability were age, pre-morbid education, productivity, and occupational category. Generally, patient outcomes improved with shorter PTA, younger age, greater pre-morbid productivity, and higher pre-morbid vocational or educational achievement. Across all prognostic groups, the best and worst good recovery rates were 65.7% and 10.9%, respectively, and the best and worst severe disability rates were 3.9% and 64.1%. Predictability in test data sets ranged from C-statistic of 0.691 (year-1; confidence interval [CI], 0.675, 0.711) to 0.731 (year-2; CI, 0.724, 0.738). In conclusion, we developed a clinically useful tool to provide prognostic information on long-term functional outcomes for adult survivors of moderate and severe closed TBI. Predictive accuracy for GOS level was demonstrated in an

Using base rates of low scores to interpret the ANAM4 TBI-MIL battery following mild traumatic brain injury.

PubMed

Ivins, Brian J; Lange, Rael T; Cole, Wesley R; Kane, Robert; Schwab, Karen A; Iverson, Grant L

2015-02-01

Base rates of low ANAM4 TBI-MIL scores were calculated in a convenience sample of 733 healthy male active duty soldiers using available military reference values for the following cutoffs: ≤2nd percentile (2 SDs), ≤5th percentile, <10th percentile, and <16th percentile (1 SD). Rates of low scores were also calculated in 56 active duty male soldiers who sustained an mTBI an average of 23 days (SD = 36.1) prior. 22.0% of the healthy sample and 51.8% of the mTBI sample had two or more scores below 1 SD (i.e., 16th percentile). 18.8% of the healthy sample and 44.6% of the mTBI sample had one or more scores ≤5th percentile. Rates of low scores in the healthy sample were influenced by cutoffs and race/ethnicity. Importantly, some healthy soldiers obtain at least one low score on ANAM4. These base rate analyses can improve the methodology for interpreting ANAM4 performance in clinical practice and research. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Rapid Isolation and Detection for RNA Biomarkers for TBI Diagnostics

DTIC Science & Technology

2016-10-01

address the qualitative result of PCR by choosing the threshold crossover cycle (CT) as a surrogate measure of the RNA/DNA originally in the sample ...include developing DEP techniques for isolation of cell-free (cf) RNA from glioblastoma exosomes and TBI samples (IRB dependent); methods for on... Sample to Answer diagnostics. 15. SUBJECT TERMS 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF

Changing the Odds A North Carolina family's search to help those with TBI

MedlinePlus

... Bar Home Current Issue Past Issues Cover Story: Traumatic Brain Injury Changing the Odds A North Carolina family's search ... his. But the 1984 crash left him with traumatic brain injury (TBI)—and changed his family's life forever. "Back ...

The effect of mild traumatic brain injury on peripheral nervous system pathology in wild-type mice and the G93A mutant mouse model of motor neuron disease.

PubMed

Evans, T M; Jaramillo, C A; Sataranatarajan, K; Watts, L; Sabia, M; Qi, W; Van Remmen, H

2015-07-09

Traumatic brain injury (TBI) is associated with a risk of neurodegenerative disease. Some suggest a link between TBI and motor neuron disease (MND), including amyotrophic lateral sclerosis (ALS). To investigate the potential mechanisms linking TBI to MND, we measured motor function and neuropathology following mild-TBI in wild-type and a transgenic model of ALS, G93A mutant mice. Mild-TBI did not alter the lifespan of G93A mice or age of onset; however, rotarod performance was impaired in G93A verses wild-type mice. Grip strength was reduced only in G93A mice after mild-TBI. Increased electromyography (EMG) abnormalities and markers of denervation (AchR, Runx1) indicate that mild-TBI may result in peripheral effects that are exaggerated in G93A mice. Markers of inflammation (cell edema, astrogliosis and microgliosis) were detected at 24 and 72h in the brain and spinal cord in wild-type and G93A mice. Levels of F2-isoprostanes, a marker of oxidative stress, were increased in the spinal cord 24h post mild-TBI in wild-type mice but were not affected by TBI in G93A mice. In summary, our data demonstrate that mild-TBI induces inflammation and oxidative stress and negatively impacts muscle denervation and motor performance, suggesting mild-TBI can potentiate motor neuron pathology and influence the development of MND in mice. Published by Elsevier Ltd.

Behavioral inhibition and activation systems in traumatic brain injury.

PubMed

Wong, Christina G; Rapport, Lisa J; Meachen, Sarah-Jane; Hanks, Robin A; Lumley, Mark A

2016-11-01

Personality has been linked to cognitive appraisal and health outcomes; however, research specific to traumatic brain injury (TBI) has been sparse. Gray's theory of behavioral inhibition system and behavioral activation system (BIS/BAS) offers a neurobiologic view of personality that may be especially relevant to neurobehavioral change associated with TBI. The present study examined theoretical and psychometric issues of using the BIS/BAS scale among adults with TBI as well as BIS/BAS personality correlates of TBI. Research Method/Design: Eighty-one adults with complicated-mild to severe TBI and 76 of their significant others (SOs) participated. Measures included the BIS/BAS scale, Positive and Negative Affect Schedule, and Awareness Questionnaire. Among adults with TBI, BIS/BAS internal consistency reliabilities were similar to those found in normative samples of adults without TBI. The TBI group endorsed significantly higher BAS than did the SO group, and injury severity was positively correlated to BAS. The SO group showed expected patterns of correlation between personality and affect; positive affect was associated with BAS, and negative affect with BIS. In contrast, in the TBI group, BAS was positively correlated to both positive and negative affect. Impaired awareness of abilities moderated the intensity of relationships between BIS/BAS and affect. TBI was associated with relatively intensified BAS (approach behavior) but not BIS (avoidance behavior). The observed pattern is consistent with the neurobiology of TBI-related personality change and with theory regarding the independence of the BIS and BAS systems. The BIS/BAS scale shows promise as a personality measure in TBI. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Neuromodulation and Neurorehabilitation for Treatment of Functional Deficits after TBI Plus PTSD

DTIC Science & Technology

2017-10-01

or not these changes correlate with improving neurobehavioral function. Aim III will examine the effect of rTMS on white fiber tracts and whether or...not the rTMS-related effects correlate with improving neurobehavioral function. Aim IV addresses the need to confirm rTMS safety for severe TBI. 15

Variation in Structure and Process of Care in Traumatic Brain Injury: Provider Profiles of European Neurotrauma Centers Participating in the CENTER-TBI Study.

PubMed

Cnossen, Maryse C; Polinder, Suzanne; Lingsma, Hester F; Maas, Andrew I R; Menon, David; Steyerberg, Ewout W

2016-01-01

The strength of evidence underpinning care and treatment recommendations in traumatic brain injury (TBI) is low. Comparative effectiveness research (CER) has been proposed as a framework to provide evidence for optimal care for TBI patients. The first step in CER is to map the existing variation. The aim of current study is to quantify variation in general structural and process characteristics among centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. We designed a set of 11 provider profiling questionnaires with 321 questions about various aspects of TBI care, chosen based on literature and expert opinion. After pilot testing, questionnaires were disseminated to 71 centers from 20 countries participating in the CENTER-TBI study. Reliability of questionnaires was estimated by calculating a concordance rate among 5% duplicate questions. All 71 centers completed the questionnaires. Median concordance rate among duplicate questions was 0.85. The majority of centers were academic hospitals (n = 65, 92%), designated as a level I trauma center (n = 48, 68%) and situated in an urban location (n = 70, 99%). The availability of facilities for neuro-trauma care varied across centers; e.g. 40 (57%) had a dedicated neuro-intensive care unit (ICU), 36 (51%) had an in-hospital rehabilitation unit and the organization of the ICU was closed in 64% (n = 45) of the centers. In addition, we found wide variation in processes of care, such as the ICU admission policy and intracranial pressure monitoring policy among centers. Even among high-volume, specialized neurotrauma centers there is substantial variation in structures and processes of TBI care. This variation provides an opportunity to study effectiveness of specific aspects of TBI care and to identify best practices with CER approaches.

Amelioration of rCBF and PbtO2 following TBI at high altitude by hyperbaric oxygen pre-conditioning.

PubMed

Hu, Shengli; Li, Fei; Luo, Haishui; Xia, Yongzhi; Zhang, Jiuquan; Hu, Rong; Cui, Gaoyu; Meng, Hui; Feng, Hua

2010-03-01

Hypobaric hypoxia at high altitude can lead to brain damage and pre-conditioning with hyperbaric oxygen (HBO) can reduce ischemic/hypoxic brain injury. This study investigates the effects of high altitude on traumatic brain injury (TBI) and examines the neuroprotection provided by HBO preconditioning against TBI. Rats were randomly divided into four groups: HBO pre-conditioning group (HBOP, n=10), high altitude group (HA, n=10), plain control group (PC, n=10) and plain sham operation group (sham, n=10). All groups were subjected to head trauma by weight drop device except for the sham group. Rats from each group were examined for neurological function, regional cerebral blood flow (rCBF) and brain tissue oxygen pressure (PbtO(2)) and were killed for analysis by transmission electron microscope. The score of neurological deficits in the HA group was highest, followed by the HBOP group and the PC group, respectively. Both rCBF and PbtO(2) were the lowest in the HA group. Brain morphology and structure seen via the transmission electron microscope was diminished in the HA group, while fewer pathological injuries occurred in the HBOP and PC groups. High altitude aggravates TBI significantly and HBO pre-conditioning can attenuate TBI in rats at high altitude by improvement of rCBF and PbtO(2). Pre-treatment with HBO might be beneficial for people traveling to high altitude locations.

Home-based, Online Mindfulness and Cognitive Training for Soldiers and Veterans with TBI

DTIC Science & Technology

2017-10-01

evaluated as a Quality of Life (QOL) enhancing strategy by comparing it to an active control condition (casual video games + online TBI information...Contribution to Project: Dr. Jackson has developed study website. Funding Support: Name: Jose Gallegos Project Role: Game Programmer Researcher

Mechanistic Links between PARP, NAD, and Brain Inflammation after TBI

DTIC Science & Technology

2014-10-01

metabolite which we have in prior studies shown to also suppress poly(ADP-ribose) polymerase activity and inflammatory responses) and ketogenic diet . CtBP1/2...knockout mice will be generated to test a specific mechanisms by which ketogenic diet can have anti-inflammatory effects. For all studies, outcome...inflammatory responses. (3) Ketogenic diet , begun 12 hours after TBI. CtBP1/2 knockout mice will be generated to test a specific mechanisms by which

Normalized power transmission between ABP and ICP in TBI.

PubMed

Shahsavari, S; Hallen, T; McKelvey, T; Ritzen, C; Rydenhag, B

2009-01-01

A new approach to study the pulse transmission between the cerebrovascular bed and the intracranial space is presented. In the proposed approach, the normalized power transmission between ABP and ICP has got the main attention rather than the actual power transmission. Evaluating the gain of the proposed transfer function at any single frequency can reveal how the percentage of contribution of that specific frequency component has been changed through the cerebrospinal system. The gain of the new transfer function at the fundamental cardiac frequency was utilized to evaluate the state of the brain in three TBI patients. Results were assessed using the reference evaluations achieved by a novel CT scan-based scoring scheme. In all three study cases, the gain of the transfer function showed a good capability to follow the trend of the CT scores and describe the brain state. Comparing the new transfer function with the traditional one and also the index of compensatory reserve, the proposed transfer function was found more informative about the state of the brain in the patients under study.

Neuropsychological recovery and quality-of-life in children and adolescents with growth hormone deficiency following TBI: a preliminary study.

PubMed

Wamstad, Julia B; Norwood, Kenneth W; Rogol, Alan D; Gurka, Matthew J; Deboer, Mark D; Blackman, James A; Buck, Marcia L; Kuperminc, Michelle N; Darring, Jodi G; Patrick, Peter D

2013-01-01

To compare neurocognition and quality-of-life (QoL) in a group of children and adolescents with or without growth hormone deficiency (GHD) following moderate-to-severe traumatic brain injury (TBI). Thirty-two children and adolescents were recruited from the TBI clinic at a children's hospital. Growth hormone (GH) was measured by both spontaneous overnight testing and following arginine/glucagon stimulation administration. Twenty-nine subjects participated in extensive neuropsychological assessment. GHD as measured on overnight testing was significantly associated with a variety of neurocognitive and QoL measures. Specifically, subjects with GHD had significantly (p < 0.05) lower scores on measures of visual memory and health-related quality-of-life. These scores were not explained by severity of injury or IQ (p > 0.05). GHD noted in response to provocative testing was not associated with any neurocognitive or QoL measures. GHD following TBI is common in children and adolescents. Deficits in neurocognition and QoL impact recovery after TBI. It is important to assess potential neurocognitive and QoL changes that may occur as a result of GHD. It is also important to consider the potential added benefit of overnight GH testing as compared to stimulation testing in predicting changes in neurocognition or QoL.

SU-E-T-515: Field-In-Field Compensation Technique Using Multi-Leaf Collimator to Deliver Total Body Irradiation (TBI) Dose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lakeman, T; Wang, IZ; Roswell Park Cancer Institute, Buffalo, NY

Purpose: Total body irradiation (TBI) uses large parallel-opposed radiation fields to suppress the patient's immune system and eradicate the residual cancer cells in preparation of recipient for bone marrow transplant. The manual placement of lead compensators has been used conventionally to compensate for the varying thickness through the entire body in large-field TBI. The goal of this study is to pursue utilizing the modern field-in-field (FIF) technique with the multi-leaf collimator (MLC) to more accurately and efficiently deliver dose to patients in need of TBI. Method: Treatment plans utilizing the FIF technique to deliver a total body dose were createdmore » retrospectively for patients for whom CT data had been previously acquired. Treatment fields include one pair of opposed open large fields (collimator=45°) with a specific weighting and a succession of smaller fields (collimator=90°) each with their own weighting. The smaller fields are shaped by moving MLC to block the sections of the patient which have already received close to 100% of the prescribed dose. The weighting factors for each of these fields were calculated using the attenuation coefficient of the initial lead compensators and the separation of the patient in different positions in the axial plane. Results: Dose-volume histograms (DVH) were calculated for evaluating the FIF compensation technique. The maximum body doses calculated from the DVH were reduced from the non-compensated 179.3% to 148.2% in the FIF plans, indicating a more uniform dose with the FIF compensation. All calculated monitor units were well within clinically acceptable limits and exceeded those of the original lead compensation plan by less than 50 MU (only ~1.1% increase). Conclusion: MLC FIF technique for TBI will not significantly increase the beam on time while it can substantially reduce the compensator setup time and the potential risk of errors in manually placing lead compensators.« less

To Fear Is to Gain? The Role of Fear Recognition in Risky Decision Making in TBI Patients and Healthy Controls

PubMed Central

Visser-Keizer, Annemarie C.; Westerhof-Evers, Herma J.; Gerritsen, Marleen J. J.; van der Naalt, Joukje; Spikman, Jacoba M.

2016-01-01

Fear is an important emotional reaction that guides decision making in situations of ambiguity or uncertainty. Both recognition of facial expressions of fear and decision making ability can be impaired after traumatic brain injury (TBI), in particular when the frontal lobe is damaged. So far, it has not been investigated how recognition of fear influences risk behavior in healthy subjects and TBI patients. The ability to recognize fear is thought to be related to the ability to experience fear and to use it as a warning signal to guide decision making. We hypothesized that a better ability to recognize fear would be related to a better regulation of risk behavior, with healthy controls outperforming TBI patients. To investigate this, 59 healthy subjects and 49 TBI patients were assessed with a test for emotion recognition (Facial Expression of Emotion: Stimuli and Tests) and a gambling task (Iowa Gambling Task (IGT)). The results showed that, regardless of post traumatic amnesia duration or the presence of frontal lesions, patients were more impaired than healthy controls on both fear recognition and decision making. In both groups, a significant relationship was found between better fear recognition, the development of an advantageous strategy across the IGT and less risk behavior in the last blocks of the IGT. Educational level moderated this relationship in the final block of the IGT. This study has important clinical implications, indicating that impaired decision making and risk behavior after TBI can be preceded by deficits in the processing of fear. PMID:27870900

To Fear Is to Gain? The Role of Fear Recognition in Risky Decision Making in TBI Patients and Healthy Controls.

PubMed

Visser-Keizer, Annemarie C; Westerhof-Evers, Herma J; Gerritsen, Marleen J J; van der Naalt, Joukje; Spikman, Jacoba M

2016-01-01

Fear is an important emotional reaction that guides decision making in situations of ambiguity or uncertainty. Both recognition of facial expressions of fear and decision making ability can be impaired after traumatic brain injury (TBI), in particular when the frontal lobe is damaged. So far, it has not been investigated how recognition of fear influences risk behavior in healthy subjects and TBI patients. The ability to recognize fear is thought to be related to the ability to experience fear and to use it as a warning signal to guide decision making. We hypothesized that a better ability to recognize fear would be related to a better regulation of risk behavior, with healthy controls outperforming TBI patients. To investigate this, 59 healthy subjects and 49 TBI patients were assessed with a test for emotion recognition (Facial Expression of Emotion: Stimuli and Tests) and a gambling task (Iowa Gambling Task (IGT)). The results showed that, regardless of post traumatic amnesia duration or the presence of frontal lesions, patients were more impaired than healthy controls on both fear recognition and decision making. In both groups, a significant relationship was found between better fear recognition, the development of an advantageous strategy across the IGT and less risk behavior in the last blocks of the IGT. Educational level moderated this relationship in the final block of the IGT. This study has important clinical implications, indicating that impaired decision making and risk behavior after TBI can be preceded by deficits in the processing of fear.

Loss of white matter connections after severe traumatic brain injury (TBI) and its relationship to social cognition.

PubMed

McDonald, Skye; Dalton, Katie I; Rushby, Jacqueline A; Landin-Romero, Ramon

2018-06-14

Adults with severe traumatic brain injury (TBI) often suffer poor social cognition. Social cognition is complex, requiring verbal, non-verbal, auditory, visual and affective input and integration. While damage to focal temporal and frontal areas has been implicated in disorders of social cognition after TBI, the role of white matter pathology has not been examined. In this study 17 adults with chronic, severe TBI and 17 control participants underwent structural MRI scans and Diffusion Tensor Imaging. The Awareness of Social Inference Test (TASIT) was used to assess their ability to understand emotional states, thoughts, intentions and conversational meaning in everyday exchanges. Track-based spatial statistics were used to perform voxelwise analysis of Fractional Anisotropy (FA) and Mean Diffusivity (MD) of white matter tracts associated with poor social cognitive performance. FA suggested a wide range of tracts were implicated in poor TASIT performance including tracts known to mediate, auditory localisation (planum temporale) communication between nonverbal and verbal processes in general (corpus callosum) and in memory in particular (fornix) as well as tracts and structures associated with semantics and verbal recall (left temporal lobe and hippocampus), multimodal processing and integration (thalamus, external capsule, cerebellum) and with social cognition (orbitofrontal cortex, frontopolar cortex, right temporal lobe). Even when controlling for non-social cognition, the corpus callosum, fornix, bilateral thalamus, right external capsule and right temporal lobe remained significant contributors to social cognitive performance. This study highlights the importance of loss of white matter connectivity in producing complex social information processing deficits after TBI.

TBI-Induced Formation of Toxic Tau and Its Biochemical Similarities to Tau in AD Brains

DTIC Science & Technology

2017-10-01

current study is to demonstrate that blast-induced traumatic brain injury (TBI) and Alzheimer’s disease (AD) lead to similar biochemical changes in tau...induced TBI leads to the production of a toxic form of tau that contributes to cognitive and electrophysiological impairments; 2) the formation of...3 4. Impact…………………………...…………………………………... 5 5. Changes/Problems...….……………………………………………… 6 6. Products …………………………………….……….….……………. 6 7

Effect of binasal occlusion (BNO) and base-in prisms on the visual-evoked potential (VEP) in mild traumatic brain injury (mTBI).

PubMed

Yadav, Naveen K; Ciuffreda, Kenneth J

2014-01-01

To assess quantitatively the effect and relative contribution of binasal occlusion (BNO) and base-in prisms (BI) on visually-evoked potential (VEP) responsivity in persons with mild traumatic brain injury (mTBI) and the symptom of visual motion sensitivity (VMS), as well as in visually-normal (VN) individuals. Subjects were comprised of 20 VN adults and 15 adults with mTBI and VMS. There were four test conditions: (1) conventional pattern VEP, which served as the baseline comparison condition; (2) VEP with BNO alone; (3) VEP with 2 pd BI prisms before each eye; and (4) VEP with the above BNO and BI prism combination. In mTBI, the mean VEP amplitude increased significantly in nearly all subjects (∼90%) with BNO alone. In contrast, in VN, it decreased significantly with BNO alone in all subjects (100%), as compared to the other test conditions. These objective findings were consistent with improvements in visual impressions and sensorimotor tasks in the group with mTBI. Latency remained within normal limits under all test conditions in both groups. Only the BNO condition demonstrated significant, but opposite and consistent, directional effects on the VEP amplitude in both groups. The BNO-VEP test condition may be used clinically for the objectively-based, differential diagnosis of persons suspected of having mTBI and VMS from the VNs.

Active-duty military service members’ visual representations of PTSD and TBI in masks

PubMed Central

Walker, Melissa S.; Kaimal, Girija; Gonzaga, Adele M. L.; Myers-Coffman, Katherine A.; DeGraba, Thomas J.

2017-01-01

ABSTRACT Active-duty military service members have a significant risk of sustaining physical and psychological trauma resulting in traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD). Within an interdisciplinary treatment approach at the National Intrepid Center of Excellence, service members participated in mask making during art therapy sessions. This study presents an analysis of the mask-making experiences of service members (n = 370) with persistent symptoms from combat- and mission-related TBI, PTSD, and other concurrent mood issues. Data sources included mask images and therapist notes collected over a five-year period. The data were coded and analyzed using grounded theory methods. Findings indicated that mask making offered visual representations of the self related to individual personhood, relationships, community, and society. Imagery themes referenced the injury, relational supports/losses, identity transitions/questions, cultural metaphors, existential reflections, and conflicted sense of self. These visual insights provided an increased understanding of the experiences of service members, facilitating their recovery. PMID:28452610

Active-duty military service members' visual representations of PTSD and TBI in masks.

PubMed

Walker, Melissa S; Kaimal, Girija; Gonzaga, Adele M L; Myers-Coffman, Katherine A; DeGraba, Thomas J

2017-12-01

Active-duty military service members have a significant risk of sustaining physical and psychological trauma resulting in traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD). Within an interdisciplinary treatment approach at the National Intrepid Center of Excellence, service members participated in mask making during art therapy sessions. This study presents an analysis of the mask-making experiences of service members (n = 370) with persistent symptoms from combat- and mission-related TBI, PTSD, and other concurrent mood issues. Data sources included mask images and therapist notes collected over a five-year period. The data were coded and analyzed using grounded theory methods. Findings indicated that mask making offered visual representations of the self related to individual personhood, relationships, community, and society. Imagery themes referenced the injury, relational supports/losses, identity transitions/questions, cultural metaphors, existential reflections, and conflicted sense of self. These visual insights provided an increased understanding of the experiences of service members, facilitating their recovery.

Increased non-relapse mortality due to high-dose cytarabine plus CY/TBI in BMT/PBSCT for acute lymphoblastic leukaemia in adults.

PubMed

Arai, Yasuyuki; Kondo, Tadakazu; Shigematsu, Akio; Tanaka, Junji; Ohashi, Kazuteru; Fukuda, Takahiro; Kawakita, Toshiro; Mori, Takehiko; Hoshino, Takumi; Onizuka, Makoto; Ozawa, Yukiyasu; Yoshida, Shuro; Ueda, Yasunori; Mizuno, Ishikazu; Atsuta, Yoshiko; Mizuta, Shuichi

2017-07-01

The efficacy of high-dose cytarabine (HDCA) plus cyclophosphamide/total-body irradiation (CY/TBI) has been proved in cord blood transplantation (CBT) for acute lymphoblastic leukaemia (ALL), but not in bone marrow or peripheral blood stem cell transplantation (BMT/PBSCT). In this cohort study, we compared the prognosis of CY/TBI (N = 1244) and HDCA/CY/TBI (N = 316) regimens in BMT/PBSCT for ALL. The addition of HDCA decreased post-transplant relapse, while significantly increasing non-relapse mortality (risk ratio, 1·33), and overall survival was not improved. The positive effects of HDCA reported in CBT cannot be extrapolated to BMT/PBSCT, and HDCA may not be recommended in these procedures. © 2017 John Wiley & Sons Ltd.

TBIdoc: 3D content-based CT image retrieval system for traumatic brain injury

NASA Astrophysics Data System (ADS)

Li, Shimiao; Gong, Tianxia; Wang, Jie; Liu, Ruizhe; Tan, Chew Lim; Leong, Tze Yun; Pang, Boon Chuan; Lim, C. C. Tchoyoson; Lee, Cheng Kiang; Tian, Qi; Zhang, Zhuo

2010-03-01

Traumatic brain injury (TBI) is a major cause of death and disability. Computed Tomography (CT) scan is widely used in the diagnosis of TBI. Nowadays, large amount of TBI CT data is stacked in the hospital radiology department. Such data and the associated patient information contain valuable information for clinical diagnosis and outcome prediction. However, current hospital database system does not provide an efficient and intuitive tool for doctors to search out cases relevant to the current study case. In this paper, we present the TBIdoc system: a content-based image retrieval (CBIR) system which works on the TBI CT images. In this web-based system, user can query by uploading CT image slices from one study, retrieval result is a list of TBI cases ranked according to their 3D visual similarity to the query case. Specifically, cases of TBI CT images often present diffuse or focal lesions. In TBIdoc system, these pathological image features are represented as bin-based binary feature vectors. We use the Jaccard-Needham measure as the similarity measurement. Based on these, we propose a 3D similarity measure for computing the similarity score between two series of CT slices. nDCG is used to evaluate the system performance, which shows the system produces satisfactory retrieval results. The system is expected to improve the current hospital data management in TBI and to give better support for the clinical decision-making process. It may also contribute to the computer-aided education in TBI.

School Psychologists' Knowledge and Self-Efficacy in Working with Students with TBI

ERIC Educational Resources Information Center

Glang, Ann E.; McCart, Melissa; Moore, Christabelle L.; Davies, Susan

2017-01-01

Approximately 145,000 U.S. children experience lasting effects of traumatic brain injury (TBI) that manifest in social, behavioural, physical, and cognitive challenges in the school setting. School psychologists have an essential role in identifying students who need support and in determining eligibility under the Individuals with Disabilities…

Differences in Brain Metabolic Impairment between Chronic Mild/Moderate TBI Patients with and without Visible Brain Lesions Based on MRI.

PubMed

Ito, Keiichi; Asano, Yoshitaka; Ikegame, Yuka; Shinoda, Jun

2016-01-01

Introduction. Many patients with mild/moderate traumatic brain injury (m/mTBI) in the chronic stage suffer from executive brain function impairment. Analyzing brain metabolism is important for elucidating the pathological mechanisms associated with their symptoms. This study aimed to determine the differences in brain glucose metabolism between m/mTBI patients with and without visible traumatic brain lesions based on MRI. Methods. Ninety patients with chronic m/mTBI due to traffic accidents were enrolled and divided into two groups based on their MRI findings. Group A comprised 50 patients with visible lesions. Group B comprised 40 patients without visible lesions. Patients underwent FDG-PET scans following cognitive tests. FDG-PET images were analyzed using voxel-by-voxel univariate statistical tests. Results. There were no significant differences in the cognitive tests between Group A and Group B. Based on FDG-PET findings, brain metabolism significantly decreased in the orbital gyrus, cingulate gyrus, and medial thalamus but increased in the parietal and occipital convexity in Group A compared with that in the control. Compared with the control, patients in Group B exhibited no significant changes. Conclusions. These results suggest that different pathological mechanisms may underlie cognitive impairment in m/mTBI patients with and without organic brain damage.

The Controlled Cortical Impact Model: Applications, Considerations for Researchers, and Future Directions

PubMed Central

Osier, Nicole D.; Dixon, C. Edward

2016-01-01

Controlled cortical impact (CCI) is a mechanical model of traumatic brain injury (TBI) that was developed nearly 30 years ago with the goal of creating a testing platform to determine the biomechanical properties of brain tissue exposed to direct mechanical deformation. Initially used to model TBIs produced by automotive crashes, the CCI model rapidly transformed into a standardized technique to study TBI mechanisms and evaluate therapies. CCI is most commonly produced using a device that rapidly accelerates a rod to impact the surgically exposed cortical dural surface. The tip of the rod can be varied in size and geometry to accommodate scalability to difference species. Typically, the rod is actuated by a pneumatic piston or electromagnetic actuator. With some limits, CCI devices can control the velocity, depth, duration, and site of impact. The CCI model produces morphologic and cerebrovascular injury responses that resemble certain aspects of human TBI. Commonly observed are graded histologic and axonal derangements, disruption of the blood–brain barrier, subdural and intra-parenchymal hematoma, edema, inflammation, and alterations in cerebral blood flow. The CCI model also produces neurobehavioral and cognitive impairments similar to those observed clinically. In contrast to other TBI models, the CCI device induces a significantly pronounced cortical contusion, but is limited in the extent to which it models the diffuse effects of TBI; a related limitation is that not all clinical TBI cases are characterized by a contusion. Another perceived limitation is that a non-clinically relevant craniotomy is performed. Biomechanically, this is irrelevant at the tissue level. However, craniotomies are not atraumatic and the effects of surgery should be controlled by including surgical sham control groups. CCI devices have also been successfully used to impact closed skulls to study mild and repetitive TBI. Future directions for CCI research surround continued

Evolving hypopituitarism as a consequence of traumatic brain injury (TBI) in childhood - call for attention.

PubMed

Medic-Stojanoska, Milica; Pekic, Sandra; Curic, Nikola; Djilas-Ivanovic, Dragana; Popovic, Vera

2007-06-01

Hypopituitarism is a common complication of TBI in long-term survivors, more frequent than previously realized. It may be partial or complete, sometimes very subtle without visible lesions in hypothalamo-pituitary region and is diagnosed only by biochemical means. Neuroendocrine abnormalities caused by TBI may have significant implications for the recovery and rehabilitation of these patients. The subjects at risk are those who have suffered moderate to severe trauma, although mild intensity trauma may precede hypopituitarism also. Particular attention should be paid to this problem in children and adolescents. We describe a patient with hypopituitarism thought to be idiopathic due to mild head trauma which caused diabetes insipidus in childhood, gradual failure of pituitary hormones during the period of growth and development, and metabolic (dyslipidemia), physical (obesity), and cognitive impairments in the adult period.

Blast Concussion mTBI, Hypopituitarism, and Psychological Health in OIF/OEFVeterans

DTIC Science & Technology

2014-06-01

Fatigue after TBI: association with neuroendocrine abnormalities. Brain injury : [BI] 21, 559-566. Colao, A., Di Somma, C., Savanelli, M.C., De Leo ...resulting in any one of the fol- lowing: loss of consciousness ( LOC ) for 30min or less, alteration of mental state for up to 24 h (being dazed, confused...with LOC greater than 30min; penetrating head wound; seizure disorder; insulin- dependent diabetes; current or past DSM-IV diagnoses of schiz- ophrenia

Using Information from the Electronic Health Record to Improve Measurement of Unemployment in Service Members and Veterans with mTBI and Post-Deployment Stress

PubMed Central

Dillahunt-Aspillaga, Christina; Finch, Dezon; Massengale, Jill; Kretzmer, Tracy; Luther, Stephen L.; McCart, James A.

2014-01-01

Objective The purpose of this pilot study is 1) to develop an annotation schema and a training set of annotated notes to support the future development of a natural language processing (NLP) system to automatically extract employment information, and 2) to determine if information about employment status, goals and work-related challenges reported by service members and Veterans with mild traumatic brain injury (mTBI) and post-deployment stress can be identified in the Electronic Health Record (EHR). Design Retrospective cohort study using data from selected progress notes stored in the EHR. Setting Post-deployment Rehabilitation and Evaluation Program (PREP), an in-patient rehabilitation program for Veterans with TBI at the James A. Haley Veterans' Hospital in Tampa, Florida. Participants Service members and Veterans with TBI who participated in the PREP program (N = 60). Main Outcome Measures Documentation of employment status, goals, and work-related challenges reported by service members and recorded in the EHR. Results Two hundred notes were examined and unique vocational information was found indicating a variety of self-reported employment challenges. Current employment status and future vocational goals along with information about cognitive, physical, and behavioral symptoms that may affect return-to-work were extracted from the EHR. The annotation schema developed for this study provides an excellent tool upon which NLP studies can be developed. Conclusions Information related to employment status and vocational history is stored in text notes in the EHR system. Information stored in text does not lend itself to easy extraction or summarization for research and rehabilitation planning purposes. Development of NLP systems to automatically extract text-based employment information provides data that may improve the understanding and measurement of employment in this important cohort. PMID:25541956

Similar outcome after allogeneic stem cell transplantation with a modified FLAMSA conditioning protocol substituting 4 Gy TBI with treosulfan in an elderly population with high-risk AML.

PubMed

Holtick, Udo; Herling, Marco; Pflug, Natali; Chakupurakal, Geothy; Leitzke, Silke; Wolf, Dominik; Hallek, Michael; Scheid, Christof; Chemnitz, Jens M

2017-03-01

The fludarabine, amsacrine, and cytarabine (FLAMSA)-reduced-intensity conditioning (RIC) protocol has been described to be effective in patients with high-risk and refractory acute myeloic leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (aSCT). To increase safety and tolerability of the conditioning, we previously reported the feasibility to substitute the TBI component by treosulfan in elderly AML patients. We now present long-term follow-up data on patients treated with FLAMSA/treosulfan compared to the original FLAMSA/4Gy TBI protocol. We retrospectively analyzed 130 consecutive patients with high-risk or relapsed AML after aSCT following FLAMSA conditioning at our center. Fifty-eight patients were treated with FLAMSA/treosulfan due to age and/or comorbidities. Seventy-two patients were treated with FLAMSA/TBI. Median age of patients treated with FLAMSA/treosulfan was 60 years compared to 46 years in those treated with FLAMSA/TBI. The cumulative incidence of a non-relapse mortality at 4 years was 28% in FLAMSA/treosulfan patients as compared to 13% in FLAMSA/TBI. Cumulative incidence of relapse was higher in patients treated with FLAMSA/TBI (46 vs. 32%). This difference was even more prominent for patients treated in blast persistence prior to transplant (relapse incidence 70% for TBI vs. 35% for treosulfan). The overall and relapse-free survival rates at 4 years were 47 and 41%, respectively, for patients treated with FLAMSA/TBI as compared to 43 and 40% in patients treated with FLAMSA/treosulfan. These data indicate an anti-leukemic activity by FLAMSA/treosulfan especially in patients with a blast persistence prior to transplant. Older age was an independent factor for a higher non-relapse mortality. Translating FLAMSA/treosulfan to younger patients, a lower non-relapse mortality, and an improved anti-leukemic activity might add up to improved overall survival. Randomized studies are required to demonstrate an improved efficacy

SU-F-T-413: Calculation Accuracy of AAA and Acuros Using Cerrobend Blocks for TBI at 400cm

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lamichhane, N; Studenski, M

2016-06-15

Purpose: It is essential to assess the lung dose during TBI to reduce toxicity. Here we characterize the accuracy of the AAA and Acuros algorithms when using cerrobend lung shielding blocks at an extended distance for TBI. Methods: We positioned a 30×30×30 cm3 solid water slab phantom at 400 cm SSD and measured PDDs (Exradin A12 and PTW parallel plate ion chambers). A 2 cm thick, 10×10 cm2 cerrobend block was hung 2 cm in front of the phantom. This geometry was reproduced in the planning system for both AAA and Acuros. In AAA, the mass density of the cerrobendmore » block was forced to 9.38 g/cm3 and in Acuros it was forced to 8.0 g/cm3 (limited to selecting stainless steel). Three different relative electron densities (RED) were tested for each algorithm; 4.97, 6.97, and 8.97. Results: PDDs from both Acuros and AAA underestimated the delivered dose. AAA calculated that depth dose was higher for RED of 4.97 as compared to 6.97 and 8.97 but still lower than measured. There was no change in the percent depth dose with changing relative electron densities for Acuros. Conclusion: Care should be taken before using AAA or Acuros with cerrobend blocks as the planning system underestimates dose. Acuros limits the ability to modify RED when compared to AAA.« less

Evaluating the impact of treatment for sleep/wake disorders on recovery of cognition and communication in adults with chronic TBI.

PubMed

Wiseman-Hakes, Catherine; Murray, Brian; Moineddin, Rahim; Rochon, Elizabeth; Cullen, Nora; Gargaro, Judith; Colantonio, Angela

2013-01-01

To longitudinally examine objective and self-reported outcomes for recovery of cognition, communication, mood and participation in adults with traumatic brain injury (TBI) and co-morbid post-traumatic sleep/wake disorders. Prospective, longitudinal, single blind outcome study. Community-based. Ten adults with moderate-severe TBI and two adults with mild TBI and persistent symptoms aged 18-58 years. Six males and six females, who were 1-22 years post-injury and presented with self-reported sleep/wake disturbances with onset post-injury. Individualized treatments for sleep/wake disorders that included sleep hygiene recommendations, pharmacological interventions and/or treatments for sleep apnea with follow-up. Insomnia Severity Index, Beck Depression and Anxiety Inventories, Latrobe Communication Questionnaire, Speed and Capacity of Language Processing, Test of Everyday Attention, Repeatable Battery for the Assessment of Neuropsychological Status, Daily Cognitive-Communication and Sleep Profile. Group analysis revealed positive trends in change for each measure and across sub-tests of all measures. Statistically significant changes were noted in insomnia severity, p = 0.0003; depression severity, p = 0.03; language, p = 0.01; speed of language processing, p = 0.007. These results add to a small but growing body of evidence that sleep/wake disorders associated with TBI exacerbate trauma-related cognitive, communication and mood impairments. Treatment for sleep/wake disorders may optimize recovery and outcomes.

Longitudinal sex and stress hormone profiles among reproductive age and post-menopausal women after severe TBI: A case series analysis.

PubMed

Ranganathan, Prerna; Kumar, Raj G; Davis, Kendra; McCullough, Emily H; Berga, Sarah L; Wagner, Amy K

2016-01-01

To describe hormone profiles for pre-/post-menopausal women, to monitor time to resumption of menstruation among pre-menopausal women and to describe cortisol associated LH suppression and phasic variation in other sex hormones over timeMethods and procedures: This study determined amenorrhea duration and characterized acute (days 0-7) and chronic (months 1-6) gonadotropins [luteinizing hormone and follicle stimulating hormone (LH, FSH)], sex hormones (progesterone, estradiol) and stress hormone (cortisol) profiles. Women were pre-menopausal (n = 3) or post-menopausal (n = 3). Among pre-menopausal women, menstrual cycle resolution and phase association (luteal/follicular) was monitored using self-report monthly reproductive history questionnaires. This study compared post-TBI hormone profiles, stratified by menopausal status, to hormone levels from seven controls and described 6- and 12-month outcomes for these women. Consistent with functional hypothalamic amenorrhea (FHA), menstruation resumption among pre-menopausal women occurred when serum cortisol normalized to luteal phase control levels. For post-menopausal women, serum cortisol reductions corresponded with resolution of suppressed LH levels. The stress of TBI results in anovulation and central hypothalamic-pituitary-ovarian (HPG) axis suppression. Future work will examine acute/chronic consequences of post-TBI hypercortisolemia and associated HPG suppression, the temporal association of HPG suppression with other neuroendocrine adaptations and how HPG suppression impacts multidimensional recovery for women with TBI.

Predictors of informal care burden 1 year after a severe traumatic brain injury: results from the PariS-TBI study.

PubMed

Bayen, Eleonore; Pradat-Diehl, Pascale; Jourdan, Claire; Ghout, Idir; Bosserelle, Vanessa; Azerad, Sylvie; Weiss, Jean-Jacques; Joël, Marie-Eve; Aegerter, Philippe; Azouvi, Philippe

2013-01-01

To investigate predictors of informal care burden 1 year after a severe traumatic brain injury (TBI). Patients (N = 66) aged 15 years or older with severe TBI (Glasgow Coma Scale score of 8 or less) and their primary informal caregivers. Multicenter inception cohort study over 22 months in Paris and the surrounding area (PariS-TBI study). Patients' preinjury characteristics; injury severity data; outcome measures at discharge from intensive care and 1 year after the injury; Dysexecutive Questionnaire; Medical Outcome Study Short Form-36; Zarit Burden Inventory. Among the 257 survivors at discharge from acute care, 66 patient-caregiver couples were included. Primary informal caregivers were predominantly women (73%), of middle age (age, 50 years), supporting male patients (79%), of mean age of 38 years. The majority (56%) of caregivers experienced significant burden, and 44% were at risk of depression. Caregivers' impaired health status and perceived burden significantly correlated with patients' global disability (as assessed with the Glasgow Outcome Scale-Extended) and impairments of executive functions (as assessed with the Dysexecutive Questionnaire). A focused principal component analysis suggested that disability and executive dysfunctions were independent predictors of perceived burden, whereas demographics, injury severity, and Glasgow Outcome Scale at discharge from acute care did not significantly correlate with caregiver's burden. Global handicap and impairments of executive functions are independent significant predictors of caregiver burden 1 year after TBI.

Automated Gun Laying System for Self-Propelled Artillery Weapons.

DTIC Science & Technology

1980-05-30

model designed specifically to the requirements of a test bed system. The system configuration and characteristics were specified through a series of...proposed by the contractor was further defined, utilizing the M109 component information provided by the COTR. Math models were developed to predict system...data. The model used for the TB-I program did not have the capability for a remote reset function, hence it was necessary to instruct the crew (loader

Project Career: Perceived benefits of iPad apps among college students with Traumatic Brain Injury (TBI).

PubMed

Jacobs, K; Leopold, A; Hendricks, D J; Sampson, E; Nardone, A; Lopez, K B; Rumrill, P; Stauffer, C; Elias, E; Scherer, M; Dembe, J

2017-09-14

Project Career is an interprofessional five-year development project designed to improve academic and employment success of undergraduate students with a traumatic brain injury (TBI) at two- and four-year colleges and universities. Students receive technology in the form of iPad applications ("apps") to support them in and out of the classroom. To assess participants' perspectives on technology at baseline and perceived benefit of apps after 6 and 12 months of use. This article address a component of a larger study. Participants included 50 college-aged students with traumatic brain injuries. Statistical analysis included data from two Matching Person and Technology (MPT) assessment forms, including the Survey of Technology Use at baseline and the Assistive Technology Use Follow-Up Survey: Apps Currently Using, administered at 6- and 12-months re-evaluation. Analyses included frequencies and descriptives. Average scores at baseline indicated positive perspectives on technology. At 6 months, quality of life (67%) and academics (76%) improved moderately or more from the use of iPad apps. At 12 months, quality of life (65%) and academics (82%) improved moderately or more from the use of iPad apps. Students with a TBI have positive perspectives on technology use. The results on perceived benefit of apps indicated that students with a TBI (including civilians and veterans) report that the apps help them perform in daily life and academic settings.

Traumatic brain injury (TBI) outcomes in an LMIC tertiary care centre and performance of trauma scores.

PubMed

Samanamalee, Samitha; Sigera, Ponsuge Chathurani; De Silva, Ambepitiyawaduge Pubudu; Thilakasiri, Kaushila; Rashan, Aasiyah; Wadanambi, Saman; Jayasinghe, Kosala Saroj Amarasiri; Dondorp, Arjen M; Haniffa, Rashan

2018-01-08

This study evaluates post-ICU outcomes of patients admitted with moderate and severe Traumatic Brain Injury (TBI) in a tertiary neurocritical care unit in an low middle income country and the performance of trauma scores: A Severity Characterization of Trauma, Trauma and Injury Severity Score, Injury Severity Score and Revised Trauma Score in this setting. Adult patients directly admitted to the neurosurgical intensive care units of the National Hospital of Sri Lanka between 21st July 2014 and 1st October 2014 with moderate or severe TBI were recruited. A telephone administered questionnaire based on the Glasgow Outcome Scale Extended (GOSE) was used to assess functional outcome of patients at 3 and 6 months after injury. The economic impact of the injury was assessed before injury, and at 3 and 6 months after injury. One hundred and one patients were included in the study. Survival at ICU discharge, 3 and 6 months after injury was 68.3%, 49.5% and 45.5% respectively. Of the survivors at 3 months after injury, 43 (86%) were living at home. Only 19 (38%) patients had a good recovery (as defined by GOSE 7 and 8). Three months and six months after injury, respectively 25 (50%) and 14 (30.4%) patients had become "economically dependent". Selected trauma scores had poor discriminatory ability in predicting mortality. This observational study of patients sustaining moderate or severe TBI in Sri Lanka (a LMIC) reveals only 46% of patients were alive at 6 months after ICU discharge and only 20% overall attained a good (GOSE 7 or 8) recovery. The social and economic consequences of TBI were long lasting in this setting. Injury Severity Score, Revised Trauma Score, A Severity Characterization of Trauma and Trauma and Injury Severity Score, all performed poorly in predicting mortality in this setting and illustrate the need for setting adapted tools.

The item level psychometrics of the behaviour rating inventory of executive function-adult (BRIEF-A) in a TBI sample.

PubMed

Waid-Ebbs, J Kay; Wen, Pey-Shan; Heaton, Shelley C; Donovan, Neila J; Velozo, Craig

2012-01-01

To determine whether the psychometrics of the BRIEF-A are adequate for individuals diagnosed with TBI. A prospective observational study in which the BRIEF-A was collected as part of a larger study. Informant ratings of the 75-item BRIEF-A on 89 individuals diagnosed with TBI were examined to determine items level psychometrics for each of the two BRIEF-A indexes: Behaviour Rating Index (BRI) and Metacognitive Index (MI). Patients were either outpatients or at least 1 year post-injury. Each index measured a latent trait, separating individuals into five-to-six ability levels and demonstrated good reliability (0.94 and 0.96). Four items were identified that did not meet the infit criteria. The results provide support for the use of the BRIEF-A as a supplemental assessment of executive function in TBI populations. However, further validation is needed with other measures of executive function. Recommendations include use of the index scores over the Global Executive Composite score and use of the difficulty hierarchy for setting therapy goals.

An exploratory analysis linking neuropsychological testing to quantification of tractography using High Definition Fiber Tracking (HDFT) in military TBI.

PubMed

Presson, Nora; Beers, Sue R; Morrow, Lisa; Wagener, Lauren M; Bird, William A; Van Eman, Gina; Krishnaswamy, Deepa; Penderville, Joshua; Borrasso, Allison J; Benso, Steven; Puccio, Ava; Fissell, Catherine; Okonkwo, David O; Schneider, Walter

2015-09-01

To realize the potential value of tractography in traumatic brain injury (TBI), we must identify metrics that provide meaningful information about functional outcomes. The current study explores quantitative metrics describing the spatial properties of tractography from advanced diffusion imaging (High Definition Fiber Tracking, HDFT). In a small number of right-handed males from military TBI (N = 7) and civilian control (N = 6) samples, both tract homologue symmetry and tract spread (proportion of brain mask voxels contacted) differed for several tracts among civilian controls and extreme groups in the TBI sample (high scorers and low scorers) for verbal recall, serial reaction time, processing speed index, and trail-making. Notably, proportion of voxels contacted in the arcuate fasciculus distinguished high and low performers on the CVLT-II and PSI, potentially reflecting linguistic task demands, and GFA in the left corticospinal tract distinguished high and low performers in PSI and Trail Making Test Part A, potentially reflecting right hand motor response demands. The results suggest that, for advanced diffusion imaging, spatial properties of tractography may add analytic value to measures of tract anisotropy.

Automated Neuropsychological Assessment Metrics (ANAM) Traumatic Brain Injury (TBI): Human Factors Assessment

DTIC Science & Technology

2011-07-01

Lindsay, Cory Overby, Angela Jeter, Petra E. Alfred, Gary L. Boykin, Carita DeVilbiss, and Raymond Bateman ARL-TN-0440 July 2011...Neuropsychological Assessment Metrics (ANAM) Traumatic Brain Injury (TBI): Human Factors Assessment Valerie J. Rice, Petra E. Alfred, Gary L. Boykin...Angela Jeter*, Petra E. Alfred, Gary L. Boykin, Carita DeVilbiss, and Raymond Bateman 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT

Traumatic Brain Injury – Modeling Neuropsychiatric Symptoms in Rodents

PubMed Central

Malkesman, Oz; Tucker, Laura B.; Ozl, Jessica; McCabe, Joseph T.

2013-01-01

Each year in the US, ∼1.5 million people sustain a traumatic brain injury (TBI). Victims of TBI can suffer from chronic post-TBI symptoms, such as sensory and motor deficits, cognitive impairments including problems with memory, learning, and attention, and neuropsychiatric symptoms such as depression, anxiety, irritability, aggression, and suicidal rumination. Although partially associated with the site and severity of injury, the biological mechanisms associated with many of these symptoms – and why some patients experience differing assortments of persistent maladies – are largely unknown. The use of animal models is a promising strategy for elucidation of the mechanisms of impairment and treatment, and learning, memory, sensory, and motor tests have widespread utility in rodent models of TBI and psychopharmacology. Comparatively, behavioral tests for the evaluation of neuropsychiatric symptomatology are rarely employed in animal models of TBI and, as determined in this review, the results have been inconsistent. Animal behavioral studies contribute to the understanding of the biological mechanisms by which TBI is associated with neurobehavioral symptoms and offer a powerful means for pre-clinical treatment validation. Therefore, further exploration of the utility of animal behavioral tests for the study of injury mechanisms and therapeutic strategies for the alleviation of emotional symptoms are relevant and essential. PMID:24109476

Comparison of blast-exposed OEF/OIF veterans with and without a history of TBI symptoms on a brief computerized neuropsychological battery.

PubMed

Kalkstein, Solomon; Scott, J Cobb; Biester, Rosette; Brownlow, Janeese A; Harpaz-Rotem, Ilan; Gur, Ruben C

2017-01-01

Mild traumatic brain injuries (mild TBIs) resulting from exposure to Improvised Explosive Devices (IEDs) are highly prevalent among veterans of the wars in Iraq and Afghanistan. This exploratory study compared the neurocognitive performance of blast-exposed veterans with (n = 19) and without (n = 15) reported symptoms of mild TBI. All subjects had diagnoses of posttraumatic stress disorder (PTSD). Neurocognitive testing was administered using a well-established computerized battery, the Penn Computerized Neuropsychological Battery (CNB), and groups were well matched on age, race, education, and time since most recent blast exposure. Although differences were not observed on CNB accuracy scores, MANOVAs revealed slower processing speed in the mTBI group when answering correctly on tests of simple and sustained attention, with large effect sizes. Results suggest a potential speed-accuracy tradeoff in blast-related mild TBI, which should be further examined in larger samples.

Evaluating the impact of treatment for sleep/wake disorders on recovery of cognition and communication in adults with chronic TBI

PubMed Central

Murray, Brian; Moineddin, Rahim; Rochon, Elizabeth; Cullen, Nora; Gargaro, Judith; Colantonio, Angela

2013-01-01

Objective To longitudinally examine objective and self-reported outcomes for recovery of cognition, communication, mood and participation in adults with traumatic brain injury (TBI) and co-morbid post-traumatic sleep/wake disorders. Design Prospective, longitudinal, single blind outcome study. Setting Community-based. Participants Ten adults with moderate–severe TBI and two adults with mild TBI and persistent symptoms aged 18–58 years. Six males and six females, who were 1–22 years post-injury and presented with self-reported sleep/wake disturbances with onset post-injury. Interventions Individualized treatments for sleep/wake disorders that included sleep hygiene recommendations, pharmacological interventions and/or treatments for sleep apnea with follow-up. Main outcome measures Insomnia Severity Index, Beck Depression and Anxiety Inventories, Latrobe Communication Questionnaire, Speed and Capacity of Language Processing, Test of Everyday Attention, Repeatable Battery for the Assessment of Neuropsychological Status, Daily Cognitive-Communication and Sleep Profile. Results Group analysis revealed positive trends in change for each measure and across sub-tests of all measures. Statistically significant changes were noted in insomnia severity, p = 0.0003; depression severity, p = 0.03; language, p = 0.01; speed of language processing, p = 0.007. Conclusions These results add to a small but growing body of evidence that sleep/wake disorders associated with TBI exacerbate trauma-related cognitive, communication and mood impairments. Treatment for sleep/wake disorders may optimize recovery and outcomes. PMID:24070180

Sci-Thur PM - Colourful Interactions: Highlights 08: ARC TBI using Single-Step Optimized VMAT Fields

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hudson, Alana; Gordon, Deborah; Moore, Roseanne

Purpose: This work outlines a new TBI delivery technique to replace a lateral POP full bolus technique. The new technique is done with VMAT arc delivery, without bolus, treating the patient prone and supine. The benefits of the arc technique include: increased patient experience and safety, better dose conformity, better organ at risk sparing, decreased therapist time and reduction of therapist injuries. Methods: In this work we build on a technique developed by Jahnke et al. We use standard arc fields with gantry speeds corrected for varying distance to the patient followed by a single step VMAT optimization on amore » patient CT to increase dose inhomogeneity and to reduce dose to the lungs (vs. blocks). To compare the arc TBI technique to our full bolus technique, we produced plans on patient CTs for both techniques and evaluated several dosimetric parameters using an ANOVA test. Results and Conclusions: The arc technique is able reduce both the hot areas to the body (D2% reduced from 122.2% to 111.8% p<0.01) and the lungs (mean lung dose reduced from 107.5% to 99.1%, p<0.01), both statistically significant, while maintaining coverage (D98% = 97.8% vs. 94.6%, p=0.313, not statistically significant). We developed a more patient and therapist-friendly TBI treatment technique that utilizes single-step optimized VMAT plans. It was found that this technique was dosimetrically equivalent to our previous lateral technique in terms of coverage and statistically superior in terms of reduced lung dose.« less

Clinical and diagnostic approach to patients with hypopituitarism due to traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), and ischemic stroke (IS).

PubMed

Karamouzis, Ioannis; Pagano, Loredana; Prodam, Flavia; Mele, Chiara; Zavattaro, Marco; Busti, Arianna; Marzullo, Paolo; Aimaretti, Gianluca

2016-06-01

The hypothalamic-pituitary dysfunction attributable to traumatic brain injury (TBI), aneurysmal subarachnoid hemorrhage (SAH), and ischemic stroke (IS) has been lately highlighted. The diagnosis of TBI-induced-hypopituitarism, defined as a deficient secretion of one or more pituitary hormones, is made similarly to the diagnosis of classical hypopituitarism because of hypothalamic/pituitary diseases. Hypopituitarism is believed to contribute to TBI-associated morbidity and to functional and cognitive final outcome, and quality-of-life impairment. Each pituitary hormone must be tested separately, since there is a variable pattern of hormone deficiency among patients with TBI-induced-hypopituitarism. Similarly, the SAH and IS may lead to pituitary dysfunction although the literature in this field is limited. The drive to diagnose hypopituitarism is the suspect that the secretion of one/more pituitary hormone may be subnormal. This suspicion can be based upon the knowledge that the patient has an appropriate clinical context in which hypopituitarism can be present, or a symptom known as caused by hypopituitarism. Hypopituitarism should be diagnosed as a combination of low peripheral and inappropriately normal/low pituitary hormones although their basal evaluation may be not distinctive due to pulsatile, circadian, or situational secretion of some hormones. Evaluation of the somatotroph and corticotroph axes require dynamic stimulation test (ITT for both axes, GHRH + arginine test for somatotroph axis) in order to clearly separate normal from deficient responses.

Parents and teachers reporting on a child's emotional and behavioural problems following severe traumatic brain injury (TBI): the moderating effect of time.

PubMed

Silberg, Tamar; Tal-Jacobi, Dana; Levav, Miriam; Brezner, Amichai; Rassovsky, Yuri

2015-01-01

Gathering information from parents and teachers following paediatric traumatic brain injury (TBI) has substantial clinical value for diagnostic decisions. Yet, a multi-informant approach has rarely been addressed when evaluating children at the chronic stage post-injury. In the current study, the goals were to examine (1) differences between parents' and teachers' reports on a child's emotional and behavioural problems and (2) the effect of time elapsed since injury on each rater's report. A sample of 42 parents and 42 teachers of children following severe TBI completed two standard rating scales. Receiver Operating Characteristic (ROC) curves were used to determine whether time elapsed since injury reliably distinguished children falling above and below clinical levels. Emotional-behavioural scores of children following severe TBI fell within normal range, according to both teachers and parents. Significant differences were found between parents' reports relatively close to the time of injury and 2 years post-injury. However, no such differences were observed in teachers' ratings. Parents and teachers of children following severe TBI differ in their reports on a child's emotional and behavioural problems. The present study not only underscores the importance of multiple informants, but also highlights, for the first time, the possibility that informants' perceptions may vary across time.

A Novel Mouse Model of Penetrating Brain Injury

PubMed Central

Cernak, Ibolja; Wing, Ian D.; Davidsson, Johan; Plantman, Stefan

2014-01-01

Penetrating traumatic brain injury (pTBI) has been difficult to model in small laboratory animals, such as rats or mice. Previously, we have established a non-fatal, rat model for pTBI using a modified air-rifle that accelerates a pellet, which hits a small probe that then penetrates the experimental animal’s brain. Knockout and transgenic strains of mice offer attractive tools to study biological reactions induced by TBI. Hence, in the present study, we adapted and modified our model to be used with mice. The technical characterization of the impact device included depth and speed of impact, as well as dimensions of the temporary cavity formed in a brain surrogate material after impact. Biologically, we have focused on three distinct levels of severity (mild, moderate, and severe), and characterized the acute phase response to injury in terms of tissue destruction, neural degeneration, and gliosis. Functional outcome was assessed by measuring bodyweight and motor performance on rotarod. The results showed that this model is capable of reproducing major morphological and neurological changes of pTBI; as such, we recommend its utilization in research studies aiming to unravel the biological events underlying injury and regeneration after pTBI. PMID:25374559

Blast Concussion mTBI, Hypopituitarism, and Psychological Health in OIF/OEF Veterans

DTIC Science & Technology

2014-06-01

Fatigue after TBI: association with neuroendocrine abnormalities. Brain injury : [BI] 21, 559-566. Colao, A., Di Somma, C., Savanelli, M.C., De Leo ...resulting in any one of the fol- lowing: loss of consciousness ( LOC ) for 30min or less, alteration of mental state for up to 24 h (being dazed, confused...with LOC greater than 30min; penetrating head wound; seizure disorder; insulin- dependent diabetes; current or past DSM-IV diagnoses of schiz- ophrenia

Interrelation between Neuroendocrine Disturbances and Medical Complications Encountered during Rehabilitation after TBI

PubMed Central

Renner, Caroline I. E.

2015-01-01

Traumatic brain injury is not a discrete event but an unfolding sequence of damage to the central nervous system. Not only the acute phase but also the subacute and chronic period after injury, i.e., during inpatient rehabilitation, is characterized by multiple neurotransmitter alterations, cellular dysfunction, and medical complications causing additional secondary injury. Neuroendocrine disturbances also influence neurological outcome and are easily overlooked as they often present with diffuse symptoms such as fatigue, depression, poor concentration, or a decline in overall cognitive function; these are also typical sequelae of traumatic brain injury. Furthermore, neurological complications such as hydrocephalus, epilepsy, fatigue, disorders of consciousness, paroxysmal sympathetic hyperactivity, or psychiatric-behavioural symptoms may mask and/or complicate the diagnosis of neuroendocrine disturbances, delay appropriate treatment and impede neurorehabilitation. The present review seeks to examine the interrelation between neuroendocrine disturbances with neurological complications frequently encountered after moderate to severe TBI during rehabilitation. Common neuroendocrine disturbances and medical complications and their clinical implications are discussed. PMID:26402710

Survival and Injury Outcome After TBI: Influence of Pre- and Post-Exposure to Caffeine

DTIC Science & Technology

2012-10-01

A1Rs. This notion is supported by findings that TBI in A1R knockout mice led to lethal status epilepticus (SE) (Kochanek et al., 2006). Likewise, A1R...G.E., Dixon, C.E., Schnermann, J., Jackson, E.K., 2006. Adenosine A1 receptor knockout mice develop lethal status epilepti- cus after experimental

Effect of electron contamination on in vivo dosimetry for lung block shielding during TBI

PubMed Central

Narayanasamy, Ganesh; Cruz, Wilbert; Saenz, Daniel L.; Stathakis, Sotirios; Papanikolaou, Niko

2016-01-01

Our institution performs in vivo verification measurement for each of our total body irradiation (TBI) patients with optically stimulated luminescent dosimeters (OSLD). The lung block verification measurements were commonly higher than expected. The aim of this work is to understand this discrepancy and improve the accuracy of these lung block verification measurements. Initially, the thickness of the lung block was increased to provide adequate lung sparing. Further tests revealed the increase was due to electron contamination dose emanating from the lung block. The thickness of the bolus material covering the OSLD behind the lung block was increased to offset the electron contamination. In addition, the distance from the lung block to the dosimeter was evaluated for its effect on the OSLD reading and found to be clinically insignificant over the range of variability in our clinic. The results show that the improved TBI treatment technique provides for better accuracy of measured dose in vivo and consistency of patient setup. PACS number(s): 87.53.Bn, 87.53.Kn, 87.55.N‐, 87.55.Qr PMID:27167290

Improving Balance in TBI Using a Low-Cost Customized Virtual Reality Rehabilitation Tool

DTIC Science & Technology

2017-10-01

AWARD NUMBER: W81XWH-14-2-0150 TITLE: Improving Balance in TBI Using a Low- Cost Customized Virtual Reality Rehabilitation Tool PRINCIPAL...PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 DISTRIBUTION STATEMENT: Approved for Public ...DOCUMENTATION PAGE Form Approved OMB No. 0704-0188 Public reporting burden for this collection of information is estimated to average 1 hour per

Neural Markers and Rehabilitation of Executive Functioning in Veterans with TBI and PTSD

DTIC Science & Technology

2016-10-01

Neuropsychiatry and Clinical Neurosciences and will be in print this month. 11 o Military Benefit/Impact: TBI was characterized by a number of mechanisms, of...of the Society for Neuroscience in October 2016. The baseline fMRI manuscript # 1 has been completed, and being submitted to “Biological Psychiatry...Cognitive Neuroscience and Neuroimaging”, in January 2017. We examined the association between PTSD symptom severity, impulsivity, working memory

Brain trauma and autophagy: What flies and mice can teach us about conserved responses.

PubMed

Ratliff, Eric P; Barekat, Ayeh; Lipinski, Marta M; Finley, Kim D

2016-11-01

Drosophila models have been successfully used to identify many genetic components that affect neurodegenerative disorders. Recently, there has been a growing interest in identifying innate and environmental factors that influence the individual outcomes following traumatic brain injury (TBI). This includes both severe TBI and more subtle, mild TBI (mTBI), which is common in people playing contact sports. Autophagy, as a clearance pathway, exerts protective effects in multiple neurological disease models. In a recent publication, we highlighted the development of a novel repetitive mTBI system using Drosophila, which recapitulates several phenotypes associated with trauma in mammalian models. In particular, flies subjected to mTBI exhibit an acute impairment of the macroautophagy/autophagy pathway that is restored 1 wk following traumatic injury exposure. These phenotypes closely resemble temporary autophagy defects observed in a mouse TBI model. Through these studies, we also identified methods to directly assess autophagic responses in the fly nervous system and laid the groundwork for future studies designed to identify genetic, epigenetic and environmental factors that have an impact on TBI outcomes.

SU-E-T-436: Feasibility of Using the 'Irregular Surface Compensator' Planning Feature of the Eclipse TPS for Total Body Irradiation (TBI) Treatment Planning.

PubMed

Ayan, A; Lu, L; Rong, Y; Cunningham, M; Weldon, M; Welliver, M; Woollard, J; Gupta, N

2012-06-01

To investigate the feasibility of using the Irregular Surface Compensator (ISC) planning feature of the Eclipse treatment planning system (TPS) for Total Body Irradiation (TBI). TBI treatments require that the whole body receives within +-10% of the prescribed dose. Different body parts with different thicknesses compared to the umbilicus separation may receive higher or lower doses compared to the prescribed dose. Another challenge is to keep the lung dose below 10Gy to avoid complications. To mitigate this problem, physical compensators and blocks are used during the treatment for different body parts and lungs. This method presents a challenge during the treatment delivery and prolongs the treatment time due to patient setup, in-vivo on-line dosimetric monitoring and the adjustment of the compensators frequently during the treatment. We investigated the use of ISC planning feature of Eclipse TPS which is an electronic compensation method that calculates a fluence map based on the body contour from the CT image. The fluence map is delivered with dynamic MLCs . This TBI treatment technique was tested using a Rando phantom in Head First Supine position with lateral beams at SSD=250cm.The calculated fluence were edited so that the lung received <∼10Gy for 12Gy prescription. A single fraction of 2Gy was delivered and the in-vivo measurements were performed in the neck, lung and the umbilicus by using OSLDs. OSLD measurements and the Eclipse TPS predictionswere 200.4/195.0, 162.2/168.9, and 196.1/208.9 cGy for the neck, lung and the umbilicus respectively. The feasibility of using the 'Irregular Surface Compensator' feature of Eclipse TPS for TBI treatment planning was demonstrated. Good agreement (<6%) between the predicted and measured doses was obtained. The proposed planning and delivery simplifies the compensation and blocking to achieve uniform dose distributions and reduces the treatment time. © 2012 American Association of Physicists in Medicine.

Blast Concussion mTBI, Hypopituitarism, and Psychological Health in OIF/OEF Veterans

DTIC Science & Technology

2013-04-01

theAmericanCongress of Rehabilitation Medicine (ACRM) as a head trauma resulting in any one of the fol- lowing: loss of consciousness ( LOC ) for 30min or less...participants had a history of blast exposure, head injury with LOC greater than 30min; penetrating head wound; seizure disorder; insulin- dependent...of blast exposures accompanied by acute symptoms of TBI and/or LOC in Iraq and/or Afghanistan and lifetime history of non-blast exposure head injuries

Blast Concussion mTBI, Hypopituitarism, and Psychological Health in OIF/OEF Veterans

DTIC Science & Technology

2012-04-01

of consciousness ( LOC ) for 30min or less, alteration of mental state for up to 24 h (being dazed, confused, disoriented, etc.), or loss of memory for...antecubital vein. None of the Veteran or community control participants had a history of blast exposure, head injury with LOC greater than 30min; penetrating...which specific inquiries were made regarding total number of blast exposures accompanied by acute symptoms of TBI and/or LOC in Iraq and/or Afghanistan

Neural network modeling for surgical decisions on traumatic brain injury patients.

PubMed

Li, Y C; Liu, L; Chiu, W T; Jian, W S

2000-01-01

Computerized medical decision support systems have been a major research topic in recent years. Intelligent computer programs were implemented to aid physicians and other medical professionals in making difficult medical decisions. This report compares three different mathematical models for building a traumatic brain injury (TBI) medical decision support system (MDSS). These models were developed based on a large TBI patient database. This MDSS accepts a set of patient data such as the types of skull fracture, Glasgow Coma Scale (GCS), episode of convulsion and return the chance that a neurosurgeon would recommend an open-skull surgery for this patient. The three mathematical models described in this report including a logistic regression model, a multi-layer perceptron (MLP) neural network and a radial-basis-function (RBF) neural network. From the 12,640 patients selected from the database. A randomly drawn 9480 cases were used as the training group to develop/train our models. The other 3160 cases were in the validation group which we used to evaluate the performance of these models. We used sensitivity, specificity, areas under receiver-operating characteristics (ROC) curve and calibration curves as the indicator of how accurate these models are in predicting a neurosurgeon's decision on open-skull surgery. The results showed that, assuming equal importance of sensitivity and specificity, the logistic regression model had a (sensitivity, specificity) of (73%, 68%), compared to (80%, 80%) from the RBF model and (88%, 80%) from the MLP model. The resultant areas under ROC curve for logistic regression, RBF and MLP neural networks are 0.761, 0.880 and 0.897, respectively (P < 0.05). Among these models, the logistic regression has noticeably poorer calibration. This study demonstrated the feasibility of applying neural networks as the mechanism for TBI decision support systems based on clinical databases. The results also suggest that neural networks may be a

Genetic Variation Underlying Traumatic Brain injury (TBI) and Late Onset Alzheimer’s Disease (LOAD)

DTIC Science & Technology

2017-10-01

Episodic memory trajectories (EMTs), longitudinal evaluations , Alzheimer’s Disease, Traumatic Brain Injury (TBI), dementia 3. ACCOMPLISHMENTS  What were... evaluate potential manuscripts/conference presentations etc SA3. To investigate whether rare coding variants in the loci...available WES datasets for replication Task 5. Report results and evaluate potential manuscripts/conference presentations

The pathophysiology underlying repetitive mild traumatic brain injury in a novel mouse model of chronic traumatic encephalopathy.

PubMed

Petraglia, Anthony L; Plog, Benjamin A; Dayawansa, Samantha; Dashnaw, Matthew L; Czerniecka, Katarzyna; Walker, Corey T; Chen, Michael; Hyrien, Ollivier; Iliff, Jeffrey J; Deane, Rashid; Huang, Jason H; Nedergaard, Maiken

2014-01-01

An animal model of chronic traumatic encephalopathy (CTE) is essential for further understanding the pathophysiological link between repetitive head injury and the development of chronic neurodegenerative disease. We previously described a model of repetitive mild traumatic brain injury (mTBI) in mice that encapsulates the neurobehavioral spectrum characteristic of patients with CTE. We aimed to study the pathophysiological mechanisms underlying this animal model. Our previously described model allows for controlled, closed head impacts to unanesthetized mice. Briefly, 12-week-old mice were divided into three groups: Control, single, and repetitive mTBI. Repetitive mTBI mice received six concussive impacts daily, for 7 days. Mice were then subsequently sacrificed for macro- and micro-histopathologic analysis at 7 days, 1 month, and 6 months after the last TBI received. Brain sections were immunostained for glial fibrillary acidic protein (GFAP) for astrocytes, CD68 for activated microglia, and AT8 for phosphorylated tau protein. Brains from single and repetitive mTBI mice lacked macroscopic tissue damage at all time-points. Single mTBI resulted in an acute rea ctive astrocytosis at 7 days and increased phospho-tau immunoreactivity that was present acutely and at 1 month, but was not persistent at 6 months. Repetitive mTBI resulted in a more marked neuroinflammatory response, with persistent and widespread astrogliosis and microglial activation, as well as significantly elevated phospho-tau immunoreactivity to 6-months. The neuropathological findings in this new model of repetitive mTBI resemble some of the histopathological hallmarks of CTE, including increased astrogliosis, microglial activation, and hyperphosphorylated tau protein accumulation.

Predicting outcome in severe traumatic brain injury using a simple prognostic model.

PubMed

Sobuwa, Simpiwe; Hartzenberg, Henry Benjamin; Geduld, Heike; Uys, Corrie

2014-06-17

Several studies have made it possible to predict outcome in severe traumatic brain injury (TBI) making it beneficial as an aid for clinical decision-making in the emergency setting. However, reliable predictive models are lacking for resource-limited prehospital settings such as those in developing countries like South Africa. To develop a simple predictive model for severe TBI using clinical variables in a South African prehospital setting. All consecutive patients admitted at two level-one centres in Cape Town, South Africa, for severe TBI were included. A binary logistic regression model was used, which included three predictor variables: oxygen saturation (SpO₂), Glasgow Coma Scale (GCS) and pupil reactivity. The Glasgow Outcome Scale was used to assess outcome on hospital discharge. A total of 74.4% of the outcomes were correctly predicted by the logistic regression model. The model demonstrated SpO₂ (p=0.019), GCS (p=0.001) and pupil reactivity (p=0.002) as independently significant predictors of outcome in severe TBI. Odds ratios of a good outcome were 3.148 (SpO₂ ≥ 90%), 5.108 (GCS 6 - 8) and 4.405 (pupils bilaterally reactive). This model is potentially useful for effective predictions of outcome in severe TBI.

Effects of video modelling on emerging speech in an adult with traumatic brain injury: preliminary findings.

PubMed

Nikopoulos, Christos K; Nikopoulou-Smyrni, Panagiota; Konstantopoulos, Kostas

2013-01-01

Research has shown that traumatic brain injury (TBI) can affect a person's ability to perform previously learned skills. Dysexecutive syndrome and inattention, for example, alongside a number of other cognitive and behavioural impairments such as memory loss and lack of motivation, significantly affect day-to-day functioning following TBI. This study examined the efficacy of video modelling in emerging speech in an adult male with TBI caused by an assault. In an effort to identify functional relations between this novice intervention and the target behaviour, experimental control was achieved by using within-system research methodology, overcoming difficulties of forming groups for such an highly non-homogeneous population. Across a number of conditions, the participant watched a videotape in which another adult modelled a selection of 19 spoken words. When this modelled behaviour was performed in vivo, then generalization across 76 other words in the absence of a videotape took place. It was revealed that video modelling can promote the performance of previously learned behaviours related to speech, but more significantly it can facilitate the generalization of this verbal behaviour across untrained words. Video modelling could well be added within the rehabilitation programmes for this population.

Data on amyloid precursor protein accumulation, spontaneous physical activity, and motor learning after traumatic brain injury in the triple-transgenic mouse model of Alzheimer׳s disease.

PubMed

Kishimoto, Yasushi; Shishido, Hajime; Sawanishi, Mayumi; Toyota, Yasunori; Ueno, Masaki; Kubota, Takashi; Kirino, Yutaka; Tamiya, Takashi; Kawai, Nobuyuki

2016-12-01

This data article contains supporting information regarding the research article entitled "Traumatic brain injury accelerates amyloid-β deposition and impairs spatial learning in the triple-transgenic mouse model of Alzheimer׳s disease" (H. Shishido, Y. Kishimoto, N. Kawai, Y. Toyota, M. Ueno, T. Kubota, Y. Kirino, T. Tamiya, 2016) [1]. Triple-transgenic (3×Tg)-Alzheimer׳s disease (AD) model mice exhibited significantly poorer spatial learning than sham-treated 3×Tg-AD mice 28 days after traumatic brain injury (TBI). Correspondingly, amyloid-β (Aβ) deposition within the hippocampus was significantly greater in 3×Tg-AD mice 28 days after TBI. However, data regarding the short-term and long-term influences of TBI on amyloid precursor protein (APP) accumulation in AD model mice remain limited. Furthermore, there is little data showing whether physical activity and motor learning are affected by TBI in AD model mice. Here, we provide immunocytochemistry data confirming that TBI induces significant increases in APP accumulation in 3×Tg-AD mice at both 7 days and 28 days after TBI. Furthermore, 3×Tg-AD model mice exhibit a reduced ability to acquire conditioned responses (CRs) during delay eyeblink conditioning compared to sham-treated 3×Tg-AD model mice 28 days after TBI. However, physical activity and motor performance are not significantly changed in TBI-treated 3×Tg-AD model mice.

Sex-related responses after traumatic brain injury: Considerations for preclinical modeling.

PubMed

Späni, Claudia B; Braun, David J; Van Eldik, Linda J

2018-05-18

Traumatic brain injury (TBI) has historically been viewed as a primarily male problem, since men are more likely to experience a TBI because of more frequent participation in activities that increase risk of head injuries. This male bias is also reflected in preclinical research where mostly male animals have been used in basic and translational science. However, with an aging population in which TBI incidence is increasingly sex-independent due to falls, and increasing female participation in high-risk activities, the attention to potential sex differences in TBI responses and outcomes will become more important. These considerations are especially relevant in designing preclinical animal models of TBI that are more predictive of human responses and outcomes. This review characterizes sex differences following TBI with a special emphasis on the contribution of the female sex hormones, progesterone and estrogen, to these differences. This information is potentially important in developing and customizing TBI treatments. Copyright © 2018 Elsevier Inc. All rights reserved.

Evaluation of cerebral-cardiac syndrome using echocardiography in a canine model of acute traumatic brain injury.

PubMed

Qian, Rong; Yang, Weizhong; Wang, Xiumei; Xu, Zhen; Liu, Xiaodong; Sun, Bing

2015-01-01

Previous studies have confirmed that traumatic brain injury (TBI) can induce general adaptation syndrome (GAS), which subsequently results in myocardial dysfunction and damage in some patients with acute TBI; this condition is also termed as cerebral-cardiac syndrome. However, most clinicians ignore the detection and treatment of myocardial dysfunction, and instead concentrate only on the serious neural damage that is observed in acute TBI, which is one of the most important fatal factors. Therefore, clarification is urgently needed regarding the relationship between TBI and myocardial dysfunction. In the present study, we evaluated 18 canine models of acute TBI, by using real-time myocardial contrast echocardiography and strain rate imaging to accurately evaluate myocardial function and regional microcirculation, including the strain rate of the different myocardial segments, time-amplitude curves, mean ascending slope of the curve, and local myocardial blood flow. Our results suggest that acute TBI often results in cerebral-cardiac syndrome, which rapidly progresses to the serious stage within 3 days. This study is the first to provide comprehensive ultrasonic characteristics of cerebral-cardiac syndrome in an animal model of TBI.

Loss to Follow-Up and Social Background in an Inception Cohort of Patients With Severe Traumatic Brain Injury: Results From the PariS-TBI Study.

PubMed

Jourdan, Claire; Bayen, Eleonore; Bahrami, Stephane; Ghout, Idir; Darnoux, Emmanuelle; Azerad, Sylvie; Ruet, Alexis; Vallat-Azouvi, Claire; Weiss, Jean-Jacques; Aegerter, Philippe; Mateo, Joaquim; Vigue, Bernard; Tazarourte, Karim; Pradat-Diehl, Pascale; Azouvi, Philippe

2016-01-01

To assess determinants of loss to follow-up (FU) at 2 time points of an inception traumatic brain injury (TBI) cohort. The PariS-TBI study consecutively included 504 adults with severe TBI on the accident scene (76% male, mean age 42 years, mean Glasgow Coma Scale 5). No exclusion criteria were used. Loss to FU at 1 and 4 years was defined among survivors as having no outcome data other than survival status. Among 257 1-year survivors, 118 (47%) were lost to FU at 1 year and 98 (40%) at 4 years. Main reasons for loss to FU were impossibility to achieve contact (109 at 1 year, 52 at 4 years) and refusal to participate (respectively 5 and 24). At 1 year, individuals not working preinjury or with nonaccidental traumas were more often lost to FU in univariate and multivariable analyses. At 4 years, loss to FU was significantly associated with preinjury alcohol abuse and unemployment. Relationship with injury severity was not significant. Socially disadvantaged persons are underrepresented in TBI outcome research. It could result in overestimation of outcome and biased estimates of sociodemographic characteristics' effects. These persons, particularly unemployed individuals, require special attention in clinical practice.

Immediate, but Not Delayed, Microsurgical Skull Reconstruction Exacerbates Brain Damage in Experimental Traumatic Brain Injury Model

PubMed Central

Lau, Tsz; Kaneko, Yuji; van Loveren, Harry; Borlongan, Cesario V.

2012-01-01

Moderate to severe traumatic brain injury (TBI) often results in malformations to the skull. Aesthetic surgical maneuvers may offer normalized skull structure, but inconsistent surgical closure of the skull area accompanies TBI. We examined whether wound closure by replacement of skull flap and bone wax would allow aesthetic reconstruction of the TBI-induced skull damage without causing any detrimental effects to the cortical tissue. Adult male Sprague-Dawley rats were subjected to TBI using the controlled cortical impact (CCI) injury model. Immediately after the TBI surgery, animals were randomly assigned to skull flap replacement with or without bone wax or no bone reconstruction, then were euthanized at five days post-TBI for pathological analyses. The skull reconstruction provided normalized gross bone architecture, but 2,3,5-triphenyltetrazolium chloride and hematoxylin and eosin staining results revealed larger cortical damage in these animals compared to those that underwent no surgical maneuver at all. Brain swelling accompanied TBI, especially the severe model, that could have relieved the intracranial pressure in those animals with no skull reconstruction. In contrast, the immediate skull reconstruction produced an upregulation of the edema marker aquaporin-4 staining, which likely prevented the therapeutic benefits of brain swelling and resulted in larger cortical infarcts. Interestingly, TBI animals introduced to a delay in skull reconstruction (i.e., 2 days post-TBI) showed significantly reduced edema and infarcts compared to those exposed to immediate skull reconstruction. That immediate, but not delayed, skull reconstruction may exacerbate TBI-induced cortical tissue damage warrants a careful consideration of aesthetic repair of the skull in TBI. PMID:22438975

Hydrocephalus during rehabilitation following severe TBI. Relation to recovery, outcome, and length of stay.

PubMed

Linnemann, Mia; Tibæk, Maiken; Kammersgaard, Lars Peter

2014-01-01

Post traumatic hydrocephalus (PTH) is a frequent complication during rehabilitation following severe TBI. However, the diagnosis of PTH is not straightforward and despite shunting recovery may be delayed. To study the influence of PTH on recovery and outcome during rehabilitation. We studied 417 patients with severe TBI admitted consecutively to a single hospital-based neurorehabilitation department serving Eastern Denmark between 2000 and 2010. Demographics (age and gender) and clinical characteristics (length of acute treatment, post traumatic amnesia (PTA), level of consciousness, injury severity (ISS), and admission FIM™), and PTH were related to recovery (discharge FIM™), outcome (GOS), and length of rehabilitation stay. Patients with PTH were older, brain injury more severe, and acute treatment was longer. At discharge they had more disability, longer rehabilitation stays, and unfavorable outcome. However, after adjusted multiple regression analyses PTH was not associated with disability at discharge or outcome. Instead, PTH was associated with longer stay for rehabilitation. Shunting for PTH does not affect recovery and outcome per se, but prolongs lengths of stay by almost 3 weeks. Therefore, patients treated for PTH are as likely to benefit from rehabilitation as patients without, but require longer rehabilitation stays.

Ethnographic analysis of traumatic brain injury patients in the national Model Systems database.

PubMed

Burnett, Derek M; Kolakowsky-Hayner, Stephanie A; Slater, Dan; Stringer, Anthony; Bushnik, Tamara; Zafonte, Ross; Cifu, David X

2003-02-01

To compare demographics, injury characteristics, therapy service and intensity, and outcome in minority versus nonminority patients with traumatic brain injury (TBI). Retrospective analysis. Twenty medical centers. Two thousand twenty patients (men, n=1,518; women, n=502; nonminority, n=1,168; minority, n=852) with TBI enrolled in the Traumatic Brain Injury Model Systems database. Not applicable. Age, gender, marital status, education, employment status, injury severity (based on Glasgow Coma Scale [GCS] admission score, length of posttraumatic amnesia, duration of unconsciousness), intensity (hours) of therapy rendered, rehabilitation length of stay (LOS), rehabilitation charges, discharge disposition, postinjury employment status, FIM instrument change scores, and FIM efficiency scores. Independent sample t tests were used to analyze continuous variables; chi-square analyses were used to evaluate categorical data. overall, minorities were found to be mostly young men who were single, unemployed, and less well educated, with a longer work week if employed when injured. motor vehicle crashes (MVCs) predominated as the cause of injury for both groups; however, minorities were more likely to sustain injury from acts of violence and auto-versus-pedestrian crashes. Minorities also had higher GCS scores on admission and shorter LOS. Rehabilitation services: significant differences were found in the types and intensity of rehabilitation services provided; these included physical therapy, occupational therapy, and speech-language pathology, but not psychology. Minority patients who sustain TBI generally tend to be young men with less social responsibility. Although MVCs predominate as the primary etiology, acts of violence and auto-versus-pedestrian incidents are more common in the minority population. Minorities tend to have higher GCS scores at admission. Also, the type and intensity of rehabilitation services provided differed significantly for the various

Traumatic Brain Injury Incidence, Clinical Overview, and Policies in the US Military Health System Since 2000.

PubMed

Swanson, Thomas M; Isaacson, Brad M; Cyborski, Cherina M; French, Louis M; Tsao, Jack W; Pasquina, Paul F

Exposure to explosive armaments during Operation Iraqi Freedom and Operation Enduring Freedom contributed to approximately 14% of the 352 612 traumatic brain injury (TBI) diagnoses in the US military between 2000 and 2016. The US Department of Defense issued guidelines in 2009 to (1) standardize TBI diagnostic criteria; (2) classify TBI according to mechanism and severity; (3) categorize TBI symptoms as somatic, psychological, or cognitive; and (4) systematize types of care given during the acute and rehabilitation stages of TBI treatment. Polytrauma and associated psychological and neurologic conditions may create barriers to optimal rehabilitation from TBI. Given the completion of recent combat operations and the transition of TBI patients into long-term care within the US Department of Veterans Affairs system, a review of the literature concerning TBI is timely. Long-term follow-up care for patients who have sustained TBI will remain a critical issue for the US military.

SU-E-T-169: Initial Investigation into the Use of Optically Stimulated Luminescent Dosimeters (OSLDs) for In-Vivo Dosimetry of TBI Patients.

PubMed

Paloor, S; Aland, T; Mathew, J; Al-Hammadi, N; Hammoud, R

2012-06-01

To report on an initial investigation into the use of optically stimulated luminescent dosimeters (OSLDs) for in-vivo dosimetry for total body irradiation (TBI) treatments. Specifically, we report on the determination of angular dependence, sensitivity correction factors and the dose calibration factors. The OSLD investigated in our work was InLight/OSL nanoDot dosimeters (Landauer Inc.). Nanodots are 5 mm diameter, 0.2 mm thick disk-shaped Carbon-doped Al2O3, and were read using a Landauer InLight microstar reader and associated software.OSLDs were irradiated under two setup conditions: a) typical clinical reference conditions (95cm SSD, 5cm depth in solid water, 10×10 cm field size), and b) TBI conditions (520cm SSD, 5cm depth in solid water, 40×40 cm field size,). The angular dependence was checked for angles ranging ±60 degree from normal incidence. In order to directly compare the sensitivity correction factors, a common dose was delivered to the OSLDs for the two setups. Pre- and post-irradiation readings were acquired. OSLDs were optically annealed under various techniques (1) by keeping over a film view box, (2) Using multiple scan on a flat bed optical scanner and (3) Using natural room light. Under reference conditions, the calculated sensitivity correction factors of the OSLDs had a SD of 2.2% and a range of 5%. Under TBI conditions, the SD increased to 3.4% and the range to 6.0%. The variation in sensitivity correction factors between individual OSLDs across the two measurement conditions was up to 10.3%. Angular dependence of less than 1% is observed. The best bleaching method we found is to keep OSLDs for more than 3 hours on a film viewer which will reduce normalized response to less than 1%. In order to obtain the most accurate results when using OSLDs for in-vivo dosimetry for TBI treatments, sensitivity correction factors and dose calibration factors should all be determined under clinical TBI conditions. © 2012 American Association of

'I kind of figured it out': the views and experiences of people with traumatic brain injury (TBI) in using social media-self-determination for participation and inclusion online.

PubMed

Brunner, Melissa; Palmer, Stuart; Togher, Leanne; Hemsley, Bronwyn

2018-06-05

Social media can support people with communication disability to access information, social participation and support. However, little is known about the experiences of people with traumatic brain injury (TBI) who use social media to determine their needs in relation to social media use. To determine the views and experiences of adults with TBI and cognitive-communication disability on using social media, specifically: (1) the nature of their social media experience; (2) barriers and facilitators to successful use; and (3) strategies that enabled their use of social media. Thirteen adults (seven men, six women) with TBI and cognitive-communication disability were interviewed about their social media experiences, and a content thematic analysis was conducted. Participants used several social media platforms including Facebook, Twitter, Instagram and virtual gaming worlds. All but one participant used social media several times each day and all used social media for social connection. Five major themes emerged from the data: (1) getting started in social media for participation and inclusion; (2) drivers to continued use of social media; (3) manner of using social media; (4) navigating social media; and (5) an evolving sense of social media mastery. In using platforms in a variety of ways, some participants developed an evolving sense of social media mastery. Participants applied caution in using social media, tended to learn through a process of trial and error, and lacked structured supports from family, friends or health professionals. They also reported several challenges that influenced their ability to use social media, but found support from peers in using the social media platforms. This information could be used to inform interventions supporting the use of social media for people with TBI and directions for future research. Social media offers adults with TBI several opportunities to communicate and for some to develop and strengthen social relationships

Glymphatic system disruption as a mediator of brain trauma and chronic traumatic encephalopathy.

PubMed

Sullan, Molly J; Asken, Breton M; Jaffee, Michael S; DeKosky, Steven T; Bauer, Russell M

2018-01-01

Traumatic brain injury (TBI) is an increasingly important issue among veterans, athletes and the general public. Difficulties with sleep onset and maintenance are among the most commonly reported symptoms following injury, and sleep debt is associated with increased accumulation of beta amyloid (Aβ) and phosphorylated tau (p-tau) in the interstitial space. Recent research into the glymphatic system, a lymphatic-like metabolic clearance mechanism in the central nervous system (CNS) which relies on cerebrospinal fluid (CSF), interstitial fluid (ISF), and astrocytic processes, shows that clearance is potentiated during sleep. This system is damaged in the acute phase following mTBI, in part due to re-localization of aquaporin-4 channels away from astrocytic end feet, resulting in reduced potential for waste removal. Long-term consequences of chronic dysfunction within this system in the context of repetitive brain trauma and insomnia have not been established, but potentially provide one link in the explanatory chain connecting repetitive TBI with later neurodegeneration. Current research has shown p-tau deposition in perivascular spaces and along interstitial pathways in chronic traumatic encephalopathy (CTE), pathways related to glymphatic flow; these are the main channels by which metabolic waste is cleared. This review addresses possible links between mTBI-related damage to glymphatic functioning and physiological changes found in CTE, and proposes a model for the mediating role of sleep disruption in increasing the risk for developing CTE-related pathology and subsequent clinical symptoms following repetitive brain trauma. Copyright © 2017 Elsevier Ltd. All rights reserved.

Brain-Derived Neurotrophic Factor (BDNF) in Traumatic Brain Injury-Related Mortality: Interrelationships Between Genetics and Acute Systemic and Central Nervous System BDNF Profiles.

PubMed

Failla, Michelle D; Conley, Yvette P; Wagner, Amy K

2016-01-01

Older adults have higher mortality rates after severe traumatic brain injury (TBI) compared to younger adults. Brain-derived neurotrophic factor (BDNF) signaling is altered in aging and is important to TBI given its role in neuronal survival/plasticity and autonomic function. Following experimental TBI, acute BDNF administration has not been efficacious. Clinically, genetic variation in BDNF (reduced signaling alleles: rs6265, Met-carriers; rs7124442, C-carriers) can be protective against acute mortality. Postacutely, these genotypes carry lower mortality risk in older adults and greater mortality risk among younger adults. Investigate BDNF levels in mortality/outcome following severe TBI in the context of age and genetic risk. Cerebrospinal fluid (CSF) and serum BDNF were assessed prospectively during the first week following severe TBI (n = 203) and in controls (n = 10). Age, BDNF genotype, and BDNF levels were assessed as mortality/outcome predictors. CSF BDNF levels tended to be higher post-TBI (P = .061) versus controls and were associated with time until death (P = .042). In contrast, serum BDNF levels were reduced post-TBI versus controls (P < .0001). Both gene * BDNF serum and gene * age interactions were mortality predictors post-TBI in the same multivariate model. CSF and serum BDNF tended to be negatively correlated post-TBI (P = .07). BDNF levels predicted mortality, in addition to gene * age interactions, suggesting levels capture additional mortality risk. Higher CSF BDNF post-TBI may be detrimental due to injury and age-related increases in pro-apoptotic BDNF target receptors. Negative CSF and serum BDNF correlations post-TBI suggest blood-brain barrier transit alterations. Understanding BDNF signaling in neuronal survival, plasticity, and autonomic function may inform treatment. © The Author(s) 2015.

Traumatic Brain Injury Incidence, Clinical Overview, and Policies in the US Military Health System Since 2000

PubMed Central

Isaacson, Brad M.; Cyborski, Cherina M.; French, Louis M.; Tsao, Jack W.; Pasquina, Paul F.

2017-01-01

Exposure to explosive armaments during Operation Iraqi Freedom and Operation Enduring Freedom contributed to approximately 14% of the 352 612 traumatic brain injury (TBI) diagnoses in the US military between 2000 and 2016. The US Department of Defense issued guidelines in 2009 to (1) standardize TBI diagnostic criteria; (2) classify TBI according to mechanism and severity; (3) categorize TBI symptoms as somatic, psychological, or cognitive; and (4) systematize types of care given during the acute and rehabilitation stages of TBI treatment. Polytrauma and associated psychological and neurologic conditions may create barriers to optimal rehabilitation from TBI. Given the completion of recent combat operations and the transition of TBI patients into long-term care within the US Department of Veterans Affairs system, a review of the literature concerning TBI is timely. Long-term follow-up care for patients who have sustained TBI will remain a critical issue for the US military. PMID:28135424

Variation in monitoring and treatment policies for intracranial hypertension in traumatic brain injury: a survey in 66 neurotrauma centers participating in the CENTER-TBI study.

PubMed

Cnossen, Maryse C; Huijben, Jilske A; van der Jagt, Mathieu; Volovici, Victor; van Essen, Thomas; Polinder, Suzanne; Nelson, David; Ercole, Ari; Stocchetti, Nino; Citerio, Giuseppe; Peul, Wilco C; Maas, Andrew I R; Menon, David; Steyerberg, Ewout W; Lingsma, Hester F

2017-09-06

No definitive evidence exists on how intracranial hypertension should be treated in patients with traumatic brain injury (TBI). It is therefore likely that centers and practitioners individually balance potential benefits and risks of different intracranial pressure (ICP) management strategies, resulting in practice variation. The aim of this study was to examine variation in monitoring and treatment policies for intracranial hypertension in patients with TBI. A 29-item survey on ICP monitoring and treatment was developed on the basis of literature and expert opinion, and it was pilot-tested in 16 centers. The questionnaire was sent to 68 neurotrauma centers participating in the Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. The survey was completed by 66 centers (97% response rate). Centers were mainly academic hospitals (n = 60, 91%) and designated level I trauma centers (n = 44, 67%). The Brain Trauma Foundation guidelines were used in 49 (74%) centers. Approximately 90% of the participants (n = 58) indicated placing an ICP monitor in patients with severe TBI and computed tomographic abnormalities. There was no consensus on other indications or on peri-insertion precautions. We found wide variation in the use of first- and second-tier treatments for elevated ICP. Approximately half of the centers were classified as using a relatively aggressive approach to ICP monitoring and treatment (n = 32, 48%), whereas the others were considered more conservative (n = 34, 52%). Substantial variation was found regarding monitoring and treatment policies in patients with TBI and intracranial hypertension. The results of this survey indicate a lack of consensus between European neurotrauma centers and provide an opportunity and necessity for comparative effectiveness research.

Extracorporeal shockwave enhanced regeneration of fibrocartilage in a delayed tendon-bone insertion repair model.

PubMed

Chow, Dick Ho Kiu; Suen, Pui Kit; Huang, Le; Cheung, Wing-Hoi; Leung, Kwok-Sui; Ng, Chun; Shi, San Qiang; Wong, Margaret Wan Nar; Qin, Ling

2014-04-01

Fibrous tissue is often formed in delayed healing of tendon bone insertion (TBI) instead of fibrocartilage. Extracorporeal shockwave (ESW) provides mechanical cues and upregulates expression of fibrocartilage-related makers and cytokines. We hypothesized that ESW would accelerate fibrocartilage regeneration at the healing interface in a delayed TBI healing model. Partial patellectomy with shielding at the TBI interface was performed on 32 female New Zealand White Rabbits for establishing this delayed TBI healing model. The rabbits were separated into the control and ESW group for evaluations at postoperative week 8 and 12. Shielding was removed at week 4 and a single ESW treatment was applied at week 6. Fibrocartilage regeneration was evaluated histomorphologically and immunohistochemically. Vickers hardness of the TBI matrix was measured by micro-indentation. ESW group showed higher fibrocartilage area, thickness, and proteoglycan deposition than the control in week 8 and 12. ESW increased expression of SOX9 and collagen II significantly in week 8 and 12, respectively. ESW group showed a gradual transition of hardness from bone to fibrocartilage to tendon, and had a higher Vickers hardness than the control group at week 12. In conclusion, ESW enhanced fibrocartilage regeneration at the healing interface in a delayed TBI healing model. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

NMDA receptor antagonist MK-801 reduces neuronal damage and preserves learning and memory in a rat model of traumatic brain injury.

PubMed

Han, Rui-Zhang; Hu, Jin-Jia; Weng, Yuan-Chi; Li, Ding-Feng; Huang, Yi

2009-12-01

NMDA receptor channel plays an important role in the pathophysiological process of traumatic brain injury (TBI). The present study aims to study the pathological mechanism of TBI and the impairment of learning and memory after TBI, and to investigate the mechanism of the protective effect of NMDA receptor antagonist MK-801 on learning and memory disorder after TBI. Forty Sprague-Dawley rats (weighing approximately 200 g) were randomized into 5 groups (n = 8 in each group): control group, model group, low-dose group (MK-801 0.5 mg/kg), middle-dose group (MK-801 2 mg/kg), and high-dose group (MK-801 10 mg/kg). TBI model was established using a weight-drop head injury mode. After 2-month drug treatment, learning and memory ability was evaluated by using Morris water maze test. Then the animals were sacrificed, and brain tissues were taken out for morphological and immunohistochemical assays. The ability of learning and memory was significantly impaired in the TBI model animals. Besides, the neuronal caspase-3 expression, neuronal nitric oxide synthase (nNOS)-positive neurons and OX-42-positive microglia were all increased in TBI animals. Meanwhile, the number of neuron synapses was decreased, and vacuoles degeneration could be observed in mitochondria. After MK-801 treatment at 3 different dosages, the ability of learning and memory was markedly improved, as compared to that of the TBI model animals. Moreover, neuronal caspase-3 expression, OX-42-positive microglia and nNOS-positive neurons were all significantly decreased. Meanwhile, the mitochondria degeneration was greatly inhibited. MK-801 could significantly inhibit the degeneration and apoptosis of neurons in damaged brain areas. It could also inhibit TBI-induced increase in nNOS-positive neurons and OX-42-positive microglia. Impairment in learning and memory in TBI animals could be repaired by treatment with MK-801.

Role of APOE Isforms in the Pathogenesis of TBI Induced Alzheimer’s Disease

DTIC Science & Technology

2014-10-01

the inheritance of APOe4 is the only proven genetic risk factor for sporadic Alzheimer disease (AD). Importantly, TBI is a risk factor for the...mice on human APOE genetic background were exceptionally difficult to generate. We are considering changes in the genotype of those particular groups...mediated through ABCA1. 2 Keywords Traumatic brain injury, APOE isoforms, ABCA1, Alzheimer disease, APPmice, amyloid beta, axonal injury, inflamma

Multimodal Approach to Testing the Acute Effects of Mild Traumatic Brain Injury (mTBI)

DTIC Science & Technology

2015-03-01

included several key staff changes, a major instrument acquisition, repairs and upgrades to the MEG , combined with substantial progress with patient...patients to non-head trauma controls in the first days after injury. Multiple modalities of behavioral, electrophysiological, and most strikingly, MEG ...changes were found. The MEG of all mTBI patients had delta activity in the frontal lobes that was absent in all controls. A scientific abstract on

Clinical correlates to assist with chronic traumatic encephalopathy diagnosis: Insights from a novel rodent repeat concussion model.

PubMed

Thomsen, Gretchen M; Ko, Ara; Harada, Megan Y; Ma, Annie; Wyss, Livia; Haro, Patricia; Vit, Jean-Philippe; Avalos, Pablo; Dhillon, Navpreet K; Cho, Noell; Shelest, Oksana; Ley, Eric J

2017-06-01

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease linked to repetitive head injuries. Chronic traumatic encephalopathy symptoms include changes in mood, behavior, cognition, and motor function; however, CTE is currently diagnosed only postmortem. Using a rat model of recurrent traumatic brain injury (TBI), we demonstrate rodent deficits that predict the severity of CTE-like brain pathology. Bilateral, closed-skull, mild TBI was administered once per week to 35 wild-type rats; eight rats received two injuries (2×TBI), 27 rats received five injuries (5×TBI), and 13 rats were sham controls. To determine clinical correlates for CTE diagnosis, TBI rats were separated based on the severity of rotarod deficits and classified as "mild" or "severe" and further separated into "acute," "short," and "long" based on age at euthanasia (90, 144, and 235 days, respectively). Brain atrophy, phosphorylated tau, and inflammation were assessed. All eight 2×TBI cases had mild rotarod deficiency, 11 5×TBI cases had mild deficiency, and 16 cases had severe deficiency. In one cohort of rats, tested at approximately 235 days of age, balance, rearing, and grip strength were significantly worse in the severe group relative to both sham and mild groups. At the acute time period, cortical thinning, phosphorylated tau, and inflammation were not observed in either TBI group, whereas corpus callosum thinning was observed in both TBI groups. At later time points, atrophy, tau pathology, and inflammation were increased in mild and severe TBI groups in the cortex and corpus callosum, relative to sham controls. These injury effects were exacerbated over time in the severe TBI group in the corpus callosum. Our model of repeat mild TBI suggests that permanent deficits in specific motor function tests correlate with CTE-like brain pathology. Assessing balance and motor coordination over time may predict CTE diagnosis.

Prospective memory rehabilitation using smartphones in patients with TBI: What do participants report?

PubMed

Evald, Lars

2015-01-01

Use of assistive devices has been shown to be beneficial as a compensatory memory strategy among brain injury survivors, but little is known about possible advantages and disadvantages of the technology. As part of an intervention study participants were interviewed about their experiences with the use of low-cost, off-the-shelf, unmodified smartphones combined with Internet calendars as a compensatory memory strategy. Thirteen community-dwelling patients with traumatic brain injury (TBI) received a 6-week group-based instruction in the systematic use of a smartphone as a memory compensatory aid followed by a brief structured open-ended interview regarding satisfaction with and advantages and disadvantages of the compensatory strategy. Ten of 13 participants continued to use a smartphone as their primary compensatory strategy. Audible and visual reminders were the most frequently mentioned advantages of the smartphone, and, second, the capability as an all-in-one memory device. In contrast, battery life was the most often mentioned disadvantage, followed by concerns about loss or failure of the device. Use of a smartphone seems to be a satisfactory compensatory memory strategy to many patients with TBI and smartphones come with features that are advantageous to other compensatory strategies. However, some benefits come hand-in-hand with drawbacks, such as the feeling of dependency. These aspects should be taken into account when choosing assistive technology as a memory compensatory strategy.

Evidence of increased brain amyloid in severe TBI survivors at 1, 12, and 24 months after injury: report of 2 cases.

PubMed

Gatson, Joshua W; Stebbins, Cari; Mathews, Dana; Harris, Thomas S; Madden, Christopher; Batjer, Hunt; Diaz-Arrastia, Ramon; Minei, Joseph P

2016-06-01

Traumatic brain injury (TBI) is a major risk factor for Alzheimer's disease. With respect to amyloid deposition, there are no published serial data regarding the deposition rate of amyloid throughout the brain after TBI. The authors conducted serial (18)F-AV-45 (florbetapir F18) positron emission tomography (PET) imaging in 2 patients with severe TBI at 1, 12, and 24 months after injury. A total of 12 brain regions were surveyed for changes in amyloid levels. Case 1 involved a 50-year-old man who experienced a severe TBI. Compared with the 1-month time point, of the 12 brain regions that were surveyed, a decrease in amyloid (as indicated by standard uptake value ratios) was only observed in the hippocampus (-16%, left; -12%, right) and caudate nucleus (-18%, left; -18%, right), suggesting that initial amyloid accumulation in the brain was cleared between time points 1 and 12 months after injury. Compared to the scan at 1 year, a greater increase in amyloid (+15%) was observed in the right hippocampus at the 24-month time point. The patient in Case 2 was a 37-year-old man who suffered severe trauma to the head and a subsequent stroke; he had poor cognitive/functional outcomes and underwent 1.5 years of rehabilitation. Due to a large infarct area on the injured side of the brain (right side), the authors focused primarily on brain regions affected within the left hemisphere. Compared with the 1-month scan, they only found an increase in brain amyloid within the left anterior putamen (+11%) at 12 months after injury. In contrast, decreased amyloid burden was detected in the left caudate nucleus (-48%), occipital cortex (-21%), and precuneus (-19%) brain regions at the 12-month time point, which is indicative of early accumulation and subsequent clearance. In comparison with 12-month values, more clearance was observed, since a reduction in amyloid was found at 24 months after trauma within the left anterior putamen (-12%) and occipital cortex (-15%). Also, by 24

Patient Characterization Protocols for Psychophysiological Studies of Traumatic Brain Injury and Post-TBI Psychiatric Disorders

DTIC Science & Technology

2013-07-22

injury and psychiatric disorders are receiving increased research attention, and ERP technologies are making contributions to this effort. This review has... technology like ERPs. They yield information not evi- dent in RT and allow us to fractionate the stimulus input-response output process with greater...Homaifar et al. (98), who writing specifically about depression following TBI, recommended that multiple means of assessment should be used when diagnosing

TBI-Induced Formation of Toxic Tau and Its Biochemical Similarities to Tau in AD Brains

DTIC Science & Technology

2016-10-01

onto wild-type mice markedly reduces 1) memory including contextual fear memory and spatial memory, and 2) long-term potentiation, a type of...TERMS Tau, contextual fear memory, spatial memory, synaptic plasticity, traumatic brain injury, Alzheimer’s disease 16. SECURITY CLASSIFICATION OF: 17...mechanism leading to TBI and AD. 2 KEYWORDS Tau, contextual fear memory, spatial memory, synaptic plasticity, traumatic brain injury, Alzheimer’s

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

PubMed Central

Yuh, Esther L.; Cooper, Shelly R.; Mukherjee, Pratik; Yue, John K.; Lingsma, Hester F.; Gordon, Wayne A.; Valadka, Alex B.; Okonkwo, David O.; Schnyer, David M.; Vassar, Mary J.; Maas, Andrew I.R.; Casey, Scott S.; Cheong, Maxwell; Dams-O'Connor, Kristen; Hricik, Allison J.; Inoue, Tomoo; Menon, David K.; Morabito, Diane J.; Pacheco, Jennifer L.; Puccio, Ava M.; Sinha, Tuhin K.

2014-01-01

Abstract 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. PMID:24742275

Implication of surgical procedure in the induction of headache and generalized painful sensation in a fluid percussion injury model in rats.

PubMed

da SilvaFiorin, Fernando; do Espírito Santo, Caroline Cunha; Santos, Adair Roberto Soares; Fighera, Michele Rechia; Royes, Luiz Fernando Freire

2018-06-13

This study demonstrated the effects of traumatic brain injury (TBI) and each step of the surgical procedure for a fluid percussion injury (FPI) model on periorbital allodynia. Adult male Wistar rats were divided in naive, incision, scraping, sham-TBI and TBI groups. Periorbital allodynia was evaluated using von Frey filaments, and heat hyperalgesia of the hindpaws was evaluated by a Plantar Test Apparatus. The statistical analyses revealed that the surgical procedure decreased von Frey filaments thresholds twenty-four hours after the surgery in all groups when compared to the naive group (p < 0.0001). Scraping, sham-TBI and TBI groups showed a decrease in the periorbital mechanical threshold for 35 days compared with the naive and incision groups (p < 0.0001). Only the TBI group demonstrated a significant difference in periorbital allodynia at 45 and 60 days after the injury (p < 0.01). A significant decrease in the thermal withdrawal latency of the hindpaw contralateral to the lesion was observed in the TBI group compared with the naïve group at 7 days and 28 days after the lesion (p < 0.05). This study presented in detail the effects of each stage of the surgical procedure for a FPI model on periorbital allodynia over time and characterized the TBI model for this evaluation. The FPI model is relevant for the study of headache and generalized pain in both acute and chronic phases after an injury. Copyright © 2018 Elsevier B.V. All rights reserved.

Sex-related differences in striatal dopaminergic system after traumatic brain injury.

PubMed

Xu, Xiupeng; Cao, Shengwu; Chao, Honglu; Liu, Yinlong; Ji, Jing

2016-06-01

Several studies have demonstrated alterations in the dopamine (DA) system after traumatic brain injury (TBI). Additionally, the existence of significant sex-related differences in the dopaminergic system has long been recognized. Accordingly, the purpose of the present study was to investigate whether TBI would differentially alter, in female and male mice, the expression and the function of the striatal vesicular monoamine transporter-2 (VMAT-2), an important DA transporter. After controlled cortical impact (CCI) injury, female mice showed significantly lower striatal DA concentrations and K(+)-evoked DA output. By contrast, no significant sex-related differences were observed in the mRNA and protein levels of striatal dopamine transporter (DAT) and VMAT-2 and the methamphetamine (MA)-evoked DA output. These results demonstrated clear sex-related differences in striatal VMAT-2 function in response to TBI and suggested that female mice may be more sensitive to the TBI-induced inhibition of the VMAT-2 function, as indicated by the greater degree of deficits observed when the VMAT-2 DA-storage function was inhibited by TBI. Moreover, the TBI-induced suppression of locomotion was more pronounced than female mice. Such findings highlight the need for sex-specific considerations when examining differences among brain injury conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

Self-awareness four years after severe traumatic brain injury: discordance between the patient's and relative's complaints. Results from the PariS-TBI study.

PubMed

Chesnel, Camille; Jourdan, Claire; Bayen, Eleonore; Ghout, Idir; Darnoux, Emmanuelle; Azerad, Sylvie; Charanton, James; Aegerter, Philippe; Pradat-Diehl, Pascale; Ruet, Alexis; Azouvi, Philippe; Vallat-Azouvi, Claire

2018-05-01

To evaluate the patient's awareness of his or her difficulties in the chronic phase of severe traumatic brain injury (TBI) and to determine the factors related to poor awareness. This study was part of a larger prospective inception cohort study of patients with severe TBI in the Parisian region (PariS-TBI study). Intervention/Main measures: Evaluation was carried out at four years and included the Brain Injury Complaint Questionnaire (BICoQ) completed by the patient and his or her relative as well as the evaluation of impairments, disability and quality of life. A total of 90 patient-relative pairs were included. Lack of awareness was measured using the unawareness index that corresponded to the number of discordant results between the patient and relative in the direction of under evaluation of difficulties by the patient. The only significant relationship found with lack of awareness was the subjective burden perceived by the relative (Zarit Burden Inventory) ( r = 0.5; P < 0.00001). There was no significant relationship between lack of awareness and injury severity, pre-injury socio-demographic data, cognitive impairments, mood disorders, functional independence (Barthel index), global disability (Glasgow Outcome Scale), return to work at four years or quality of life (Quality Of Life after Brain Injury scale (QOLIBRI)). Lack of awareness four years post severe TBI was not related to the severity of the initial trauma, sociodemographic data, the severity of impairments, limitations of activity and participation, or the patient's quality of life. However, poor awareness did significantly influence the weight of the burden perceived by the relative.

Independent validation of the MMPI-2-RF Somatic/Cognitive and Validity scales in TBI Litigants tested for effort.

PubMed

Youngjohn, James R; Wershba, Rebecca; Stevenson, Matthew; Sturgeon, John; Thomas, Michael L

2011-04-01

The MMPI-2 Restructured Form (MMPI-2-RF; Ben-Porath & Tellegen, 2008) is replacing the MMPI-2 as the most widely used personality test in neuropsychological assessment, but additional validation studies are needed. Our study examines MMPI-2-RF Validity scales and the newly created Somatic/Cognitive scales in a recently reported sample of 82 traumatic brain injury (TBI) litigants who either passed or failed effort tests (Thomas & Youngjohn, 2009). The restructured Validity scales FBS-r (restructured symptom validity), F-r (restructured infrequent responses), and the newly created Fs (infrequent somatic responses) were not significant predictors of TBI severity. FBS-r was significantly related to passing or failing effort tests, and Fs and F-r showed non-significant trends in the same direction. Elevations on the Somatic/Cognitive scales profile (MLS-malaise, GIC-gastrointestinal complaints, HPC-head pain complaints, NUC-neurological complaints, and COG-cognitive complaints) were significant predictors of effort test failure. Additionally, HPC had the anticipated paradoxical inverse relationship with head injury severity. The Somatic/Cognitive scales as a group were better predictors of effort test failure than the RF Validity scales, which was an unexpected finding. MLS arose as the single best predictor of effort test failure of all RF Validity and Somatic/Cognitive scales. Item overlap analysis revealed that all MLS items are included in the original MMPI-2 Hy scale, making MLS essentially a subscale of Hy. This study validates the MMPI-2-RF as an effective tool for use in neuropsychological assessment of TBI litigants.

A Porcine Model of Traumatic Brain Injury via Head Rotational Acceleration

PubMed Central

Cullen, D. Kacy; Harris, James P.; Browne, Kevin D.; Wolf, John A; Duda, John E.; Meaney, David F.; Margulies, Susan S.; Smith, Douglas H.

2017-01-01

Unique from other brain disorders, traumatic brain injury (TBI) generally results from a discrete biomechanical event that induces rapid head movement. The large size and high organization of the human brain makes it particularly vulnerable to traumatic injury from rotational accelerations that can cause dynamic deformation of the brain tissue. Therefore, replicating the injury biomechanics of human TBI in animal models presents a substantial challenge, particularly with regard to addressing brain size and injury parameters. Here we present the historical development and use of a porcine model of head rotational acceleration. By scaling up the rotational forces to account for difference in brain mass between swine and humans, this model has been shown to produce the same tissue deformations and identical neuropathologies found in human TBI. The parameters of scaled rapid angular accelerations applied for the model reproduce inertial forces generated when the human head suddenly accelerates or decelerates in falls, collisions, or blunt impacts. The model uses custom-built linkage assemblies and a powerful linear actuator designed to produce purely impulsive nonimpact head rotation in different angular planes at controlled rotational acceleration levels. Through a range of head rotational kinematics, this model can produce functional and neuropathological changes across the spectrum from concussion to severe TBI. Notably, however, the model is very difficult to employ, requiring a highly skilled team for medical management, biomechanics, neurological recovery, and specialized outcome measures including neuromonitoring, neurophysiology, neuroimaging, and neuropathology. Nonetheless, while challenging, this clinically relevant model has proven valuable for identifying mechanisms of acute and progressive neuropathologies as well as for the evaluation of noninvasive diagnostic techniques and potential neuroprotective treatments following TBI. PMID:27604725

Linking blast physics to biological outcomes in mild traumatic brain injury: Narrative review and preliminary report of an open-field blast model.

PubMed

Song, Hailong; Cui, Jiankun; Simonyi, Agnes; Johnson, Catherine E; Hubler, Graham K; DePalma, Ralph G; Gu, Zezong

2018-03-15

Blast exposures are associated with traumatic brain injury (TBI) and blast-induced TBIs are common injuries affecting military personnel. Department of Defense and Veterans Administration (DoD/VA) reports for TBI indicated that the vast majority (82.3%) has been mild TBI (mTBI)/concussion. mTBI and associated posttraumatic stress disorders (PTSD) have been called "the invisible injury" of the current conflicts in Iraq and Afghanistan. These injuries induce varying degrees of neuropathological alterations and, in some cases, chronic cognitive, behavioral and neurological disorders. Appropriate animal models of blast-induced TBI will not only assist the understanding of physical characteristics of the blast, but also help to address the potential mechanisms. This report provides a brief overview of physical principles of blast, injury mechanisms related to blast exposure, current blast animal models, and the neurological behavioral and neuropathological findings related to blast injury in experimental settings. We describe relationships between blast peak pressures and the observed injuries. We also report preliminary use of a highly reproducible and intensity-graded blast murine model carried out in open-field with explosives, and describe physical and pathological findings in this experimental model. Our results indicate close relationships between blast intensities and neuropathology and behavioral deficits, particularly at low level blast intensities relevant to mTBI. Copyright © 2016 Elsevier B.V. All rights reserved.

Development of A Novel Murine Model of Combined Radiation and Peripheral Tissue Trauma Injuries

PubMed Central

Antonic, Vlado; Jackson, Isabel L.; Ganga, Gurung; Shea-Donohue, Terez; Vujaskovic, Zeljko

2017-01-01

Detonation of a 10-kiloton nuclear bomb in an urban setting would result in >1 million casualties, the majority of which would present with combined injuries. Combined injuries, such as peripheral tissue trauma and radiation exposure, trigger inflammatory events that lead to multiple organ dysfunction (MOD) and death, with gastrointestinal (GI) and pulmonary involvement playing crucial roles. The objective of this study was to develop an animal model of combined injuries, peripheral tissue trauma (TBX animal model) combined with total body irradiation with 5% bone marrow shielding (TBI/BM5) to investigate if peripheral tissue trauma contributes to reduced survival. Male C57BL/6J mice were exposed to TBX10%, irradiation (TBI/BM5), or combined injuries (TBX10% + TBI/BM5). Experiments were conducted to evaluate mortality at day 7 after TBI/BM5. Serial euthanasia was performed at day 1, 3 and 6 or 7 after TBI/BM5 to evaluate the time course of pathophysiologic processes in combined injuries. Functional tests were performed to assess pulmonary function and GI motility. Postmortem samples of lungs and jejunum were collected to assess tissue damage. Results indicated higher lethality and shorter survival in the TBX10% +T BI/BM5 group than in the TBX10% or TBI/BM5 groups (day 1 vs. day 7 and 6, respectively). TBI/BM5 alone had no effects on the lungs but significantly impaired GI function at day 6. As expected, in the animals that received severe trauma (TBX10%), we observed impairment in lung function and delay in GI transit in the first 3 days, effects that decreased at later time points. Trauma combined with radiation (TBX10% + TBI/BM5) significantly augmented impairment of the lung and GI function in comparison to TBX10% and TBI/BM5 groups at 24 h. Histologic evaluation indicated that combined injuries caused greater tissue damage in the intestines in TBX10% + TBI/BM5 group when compared to other groups. We describe here the first combined tissue trauma

Impact of conditioning with TBI in adult patients with T-cell ALL who receive a myeloablative allogeneic stem cell transplantation: a report from the acute leukemia working party of EBMT.

PubMed

Cahu, X; Labopin, M; Giebel, S; Aljurf, M; Kyrcz-Krzemien, S; Socié, G; Eder, M; Bonifazi, F; Bunjes, D; Vigouroux, S; Michallet, M; Stelljes, M; Zuckerman, T; Finke, J; Passweg, J; Yakoub-Agha, I; Niederwieser, D; Sucak, G; Sengeløv, H; Polge, E; Nagler, A; Esteve, J; Mohty, M

2016-03-01

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a therapeutic option for adult patients with T-cell ALL (T-ALL). Meanwhile, few allo-SCT data specific to adult T-ALL have been described thus far. Specifically, the optimal myeloablative conditioning regimen is unknown. In this retrospective study, 601 patients were included. Patients received allo-SCT in CR1, CR2, CR >2 or in advanced disease in 69%, 15%, 2% and 14% of cases, respectively. With an overall follow-up of 58 months, 523 patients received a TBI-based regimen, whereas 78 patients received a chemotherapy-based regimen including IV busulfan-cyclophosphamide (IV Bu-Cy) (n=46). Unlike patients aged ⩾35 years, patients aged <35 years who received a TBI-based regimen displayed an improved outcome compared with patients who received a chemotherapy-based regimen (5-year leukemia-free survival (LFS) of 50% for TBI versus 18% for chemo-only regimen or IV Bu-Cy regimens, P=10(-5) and 10(-4), respectively). In multivariate analysis, use of TBI was associated with an improved LFS (hazard ratio (HR)=0.55 (0.34-0.86), P=0.01) and overall survival (HR=0.54 (0.34-0.87), P=0.01) in patients aged <35 years. In conclusion, younger adult patients with T-ALL entitled to receive a myeloablative allo-SCT may benefit from TBI-based regimens.

Lateral Fluid Percussion: Model of Traumatic Brain Injury in Mice

PubMed Central

Alder, Janet; Fujioka, Wendy; Lifshitz, Jonathan; Crockett, David P.; Thakker-Varia, Smita

2011-01-01

Traumatic brain injury (TBI) research has attained renewed momentum due to the increasing awareness of head injuries, which result in morbidity and mortality. Based on the nature of primary injury following TBI, complex and heterogeneous secondary consequences result, which are followed by regenerative processes 1,2. Primary injury can be induced by a direct contusion to the brain from skull fracture or from shearing and stretching of tissue causing displacement of brain due to movement 3,4. The resulting hematomas and lacerations cause a vascular response 3,5, and the morphological and functional damage of the white matter leads to diffuse axonal injury 6-8. Additional secondary changes commonly seen in the brain are edema and increased intracranial pressure 9. Following TBI there are microscopic alterations in biochemical and physiological pathways involving the release of excitotoxic neurotransmitters, immune mediators and oxygen radicals 10-12, which ultimately result in long-term neurological disabilities 13,14. Thus choosing appropriate animal models of TBI that present similar cellular and molecular events in human and rodent TBI is critical for studying the mechanisms underlying injury and repair. Various experimental models of TBI have been developed to reproduce aspects of TBI observed in humans, among them three specific models are widely adapted for rodents: fluid percussion, cortical impact and weight drop/impact acceleration 1. The fluid percussion device produces an injury through a craniectomy by applying a brief fluid pressure pulse on to the intact dura. The pulse is created by a pendulum striking the piston of a reservoir of fluid. The percussion produces brief displacement and deformation of neural tissue 1,15. Conversely, cortical impact injury delivers mechanical energy to the intact dura via a rigid impactor under pneumatic pressure 16,17. The weight drop/impact model is characterized by the fall of a rod with a specific mass on the closed

Lateral fluid percussion: model of traumatic brain injury in mice.

PubMed

Alder, Janet; Fujioka, Wendy; Lifshitz, Jonathan; Crockett, David P; Thakker-Varia, Smita

2011-08-22

Traumatic brain injury (TBI) research has attained renewed momentum due to the increasing awareness of head injuries, which result in morbidity and mortality. Based on the nature of primary injury following TBI, complex and heterogeneous secondary consequences result, which are followed by regenerative processes (1,2). Primary injury can be induced by a direct contusion to the brain from skull fracture or from shearing and stretching of tissue causing displacement of brain due to movement (3,4). The resulting hematomas and lacerations cause a vascular response (3,5), and the morphological and functional damage of the white matter leads to diffuse axonal injury (6-8). Additional secondary changes commonly seen in the brain are edema and increased intracranial pressure (9). Following TBI there are microscopic alterations in biochemical and physiological pathways involving the release of excitotoxic neurotransmitters, immune mediators and oxygen radicals (10-12), which ultimately result in long-term neurological disabilities (13,14). Thus choosing appropriate animal models of TBI that present similar cellular and molecular events in human and rodent TBI is critical for studying the mechanisms underlying injury and repair. Various experimental models of TBI have been developed to reproduce aspects of TBI observed in humans, among them three specific models are widely adapted for rodents: fluid percussion, cortical impact and weight drop/impact acceleration (1). The fluid percussion device produces an injury through a craniectomy by applying a brief fluid pressure pulse on to the intact dura. The pulse is created by a pendulum striking the piston of a reservoir of fluid. The percussion produces brief displacement and deformation of neural tissue (1,15). Conversely, cortical impact injury delivers mechanical energy to the intact dura via a rigid impactor under pneumatic pressure (16,17). The weight drop/impact model is characterized by the fall of a rod with a specific

Assessment of Cognitive Function in the Water Maze Task: Maximizing Data Collection and Analysis in Animal Models of Brain Injury.

PubMed

Whiting, Mark D; Kokiko-Cochran, Olga N

2016-01-01

Animal models play a critical role in understanding the biomechanical, pathophysiological, and behavioral consequences of traumatic brain injury (TBI). In preclinical studies, cognitive impairment induced by TBI is often assessed using the Morris water maze (MWM). Frequently described as a hippocampally dependent spatial navigation task, the MWM is a highly integrative behavioral task that requires intact functioning in numerous brain regions and involves an interdependent set of mnemonic and non-mnemonic processes. In this chapter, we review the special considerations involved in using the MWM in animal models of TBI, with an emphasis on maximizing the degree of information extracted from performance data. We include a theoretical framework for examining deficits in discrete stages of cognitive function and offer suggestions for how to make inferences regarding the specific nature of TBI-induced cognitive impairment. The ultimate goal is more precise modeling of the animal equivalents of the cognitive deficits seen in human TBI.

Effect of the Modified Glasgow Coma Scale Score Criteria for Mild Traumatic Brain Injury on Mortality Prediction: Comparing Classic and Modified Glasgow Coma Scale Score Model Scores of 13

PubMed Central

Mena, Jorge Humberto; Sanchez, Alvaro Ignacio; Rubiano, Andres M.; Peitzman, Andrew B.; Sperry, Jason L.; Gutierrez, Maria Isabel; Puyana, Juan Carlos

2011-01-01

Objective The Glasgow Coma Scale (GCS) classifies Traumatic Brain Injuries (TBI) as Mild (14–15); Moderate (9–13) or Severe (3–8). The ATLS modified this classification so that a GCS score of 13 is categorized as mild TBI. We investigated the effect of this modification on mortality prediction, comparing patients with a GCS of 13 classified as moderate TBI (Classic Model) to patients with GCS of 13 classified as mild TBI (Modified Model). Methods We selected adult TBI patients from the Pennsylvania Outcome Study database (PTOS). Logistic regressions adjusting for age, sex, cause, severity, trauma center level, comorbidities, and isolated TBI were performed. A second evaluation included the time trend of mortality. A third evaluation also included hypothermia, hypotension, mechanical ventilation, screening for drugs, and severity of TBI. Discrimination of the models was evaluated using the area under receiver operating characteristic curve (AUC). Calibration was evaluated using the Hoslmer-Lemershow goodness of fit (GOF) test. Results In the first evaluation, the AUCs were 0.922 (95 %CI, 0.917–0.926) and 0.908 (95 %CI, 0.903–0.912) for classic and modified models, respectively. Both models showed poor calibration (p<0.001). In the third evaluation, the AUCs were 0.946 (95 %CI, 0.943 – 0.949) and 0.938 (95 %CI, 0.934 –0.940) for the classic and modified models, respectively, with improvements in calibration (p=0.30 and p=0.02 for the classic and modified models, respectively). Conclusion The lack of overlap between ROC curves of both models reveals a statistically significant difference in their ability to predict mortality. The classic model demonstrated better GOF than the modified model. A GCS of 13 classified as moderate TBI in a multivariate logistic regression model performed better than a GCS of 13 classified as mild. PMID:22071923

Hepatic alterations are accompanied by changes to bile acid transporter-expressing neurons in the hypothalamus after traumatic brain injury.

PubMed

Nizamutdinov, Damir; DeMorrow, Sharon; McMillin, Matthew; Kain, Jessica; Mukherjee, Sanjib; Zeitouni, Suzanne; Frampton, Gabriel; Bricker, Paul Clint S; Hurst, Jacob; Shapiro, Lee A

2017-01-20

Annually, there are over 2 million incidents of traumatic brain injury (TBI) and treatment options are non-existent. While many TBI studies have focused on the brain, peripheral contributions involving the digestive and immune systems are emerging as factors involved in the various symptomology associated with TBI. We hypothesized that TBI would alter hepatic function, including bile acid system machinery in the liver and brain. The results show activation of the hepatic acute phase response by 2 hours after TBI, hepatic inflammation by 6 hours after TBI and a decrease in hepatic transcription factors, Gli 1, Gli 2, Gli 3 at 2 and 24 hrs after TBI. Bile acid receptors and transporters were decreased as early as 2 hrs after TBI until at least 24 hrs after TBI. Quantification of bile acid transporter, ASBT-expressing neurons in the hypothalamus, revealed a significant decrease following TBI. These results are the first to show such changes following a TBI, and are compatible with previous studies of the bile acid system in stroke models. The data support the emerging idea of a systemic influence to neurological disorders and point to the need for future studies to better define specific mechanisms of action.

Hepatic alterations are accompanied by changes to bile acid transporter-expressing neurons in the hypothalamus after traumatic brain injury

PubMed Central

Nizamutdinov, Damir; DeMorrow, Sharon; McMillin, Matthew; Kain, Jessica; Mukherjee, Sanjib; Zeitouni, Suzanne; Frampton, Gabriel; Bricker, Paul Clint S.; Hurst, Jacob; Shapiro, Lee A.

2017-01-01

Annually, there are over 2 million incidents of traumatic brain injury (TBI) and treatment options are non-existent. While many TBI studies have focused on the brain, peripheral contributions involving the digestive and immune systems are emerging as factors involved in the various symptomology associated with TBI. We hypothesized that TBI would alter hepatic function, including bile acid system machinery in the liver and brain. The results show activation of the hepatic acute phase response by 2 hours after TBI, hepatic inflammation by 6 hours after TBI and a decrease in hepatic transcription factors, Gli 1, Gli 2, Gli 3 at 2 and 24 hrs after TBI. Bile acid receptors and transporters were decreased as early as 2 hrs after TBI until at least 24 hrs after TBI. Quantification of bile acid transporter, ASBT-expressing neurons in the hypothalamus, revealed a significant decrease following TBI. These results are the first to show such changes following a TBI, and are compatible with previous studies of the bile acid system in stroke models. The data support the emerging idea of a systemic influence to neurological disorders and point to the need for future studies to better define specific mechanisms of action. PMID:28106051

Human Brain Modeling with Its Anatomical Structure and Realistic Material Properties for Brain Injury Prediction.

PubMed

Atsumi, Noritoshi; Nakahira, Yuko; Tanaka, Eiichi; Iwamoto, Masami

2018-05-01

Impairments of executive brain function after traumatic brain injury (TBI) due to head impacts in traffic accidents need to be obviated. Finite element (FE) analyses with a human brain model facilitate understanding of the TBI mechanisms. However, conventional brain FE models do not suitably describe the anatomical structure in the deep brain, which is a critical region for executive brain function, and the material properties of brain parenchyma. In this study, for better TBI prediction, a novel brain FE model with anatomical structure in the deep brain was developed. The developed model comprises a constitutive model of brain parenchyma considering anisotropy and strain rate dependency. Validation was performed against postmortem human subject test data associated with brain deformation during head impact. Brain injury analyses were performed using head acceleration curves obtained from reconstruction analysis of rear-end collision with a human whole-body FE model. The difference in structure was found to affect the regions of strain concentration, while the difference in material model contributed to the peak strain value. The injury prediction result by the proposed model was consistent with the characteristics in the neuroimaging data of TBI patients due to traffic accidents.

A multidisciplinary TBI inpatient rehabilitation programme for active duty service members as part of a randomized clinical trial.

PubMed

Braverman, S E; Spector, J; Warden, D L; Wilson, B C; Ellis, T E; Bamdad, M J; Salazar, A M

1999-06-01

To design and describe an effective rehabilitation programme for use in an ongoing trial on the efficacy of multidisciplinary brain injury rehabilitation for moderately head injury military service members. Treatment arm of a randomized control trial. US military tertiary care hospital inpatient rehabilitation programme. Sixty seven active duty military with moderate to severe TBI who were randomized to the treatment arm of the protocol. Eight week rehabilitation programme combining group and individual therapies with an inpatient milieu-oriented neuropsychological focus. Group therapies included fitness, planning and organization, cognitive skills, work skills, medication, and milieu groups, and community re-entry outings. Individual therapy included neuropsychology, work therapy, occupational therapy, and speech and language pathology. Successful return to work and return to duty. At 1 year follow-up, 64 patients returned to work (96%) and 66% (44/67) returned to duty. The described rehabilitation programme demonstrates one successful effort to rehabilitate active duty military service members with TBI who have the potential to return to duty.

Withania somnifera Extract Protects Model Neurons from In Vitro Traumatic Injury

PubMed Central

Saykally, Jessica N.; Hatic, Haris; Keeley, Kristen L.; Jain, Subhash C.; Ravindranath, Vijayalakshmi

2017-01-01

Withania somnifera has been used in traditional medicine for a variety of neural disorders. Recently, chronic neurodegenerative conditions have been shown to benefit from treatment with this extract. To evaluate the action of this extract on traumatically injured neurons, the efficacy of W. somnifera root extract as a neuroprotective agent was examined in cultured model neurons exposed to an in vitro injury system designed to mimic mild traumatic brain injury (TBI). Neuronal health was evaluated by staining with annexin V (an early, apoptotic feature) and monitoring released lactate dehydrogenase activity (a terminal cell loss parameter). Potential mechanisms underlying the observed neuroprotection were examined. Additionally, morphological changes were monitored following injury and treatment. Although no differences were found in the expression of the antioxidant transcription factor nuclear factor erythroid 2-like 2 (Nrf2) or other Nrf2-related downstream components, significant changes were seen in apoptotic signaling. Treatment with the extract resulted in an increased length of neurites projecting from the neuronal cell body after injury. W. somnifera extract treatment also resulted in reduced cell death in the model neuron TBI system. The cell death factor Bax was involved (its expression was reduced 2-fold by the treatment) and injury-induced reduction in neurite lengths and numbers was reversed by the treatment. This all indicates that W. somnifera root extract was neuroprotective and could have therapeutic potential to target factors involved in secondary injury and long-term sequelae of mild TBI. PMID:28933215

Withania somnifera Extract Protects Model Neurons from In Vitro Traumatic Injury.

PubMed

Saykally, Jessica N; Hatic, Haris; Keeley, Kristen L; Jain, Subhash C; Ravindranath, Vijayalakshmi; Citron, Bruce A

2017-07-01

Withania somnifera has been used in traditional medicine for a variety of neural disorders. Recently, chronic neurodegenerative conditions have been shown to benefit from treatment with this extract. To evaluate the action of this extract on traumatically injured neurons, the efficacy of W. somnifera root extract as a neuroprotective agent was examined in cultured model neurons exposed to an in vitro injury system designed to mimic mild traumatic brain injury (TBI). Neuronal health was evaluated by staining with annexin V (an early, apoptotic feature) and monitoring released lactate dehydrogenase activity (a terminal cell loss parameter). Potential mechanisms underlying the observed neuroprotection were examined. Additionally, morphological changes were monitored following injury and treatment. Although no differences were found in the expression of the antioxidant transcription factor nuclear factor erythroid 2-like 2 (Nrf2) or other Nrf2-related downstream components, significant changes were seen in apoptotic signaling. Treatment with the extract resulted in an increased length of neurites projecting from the neuronal cell body after injury. W. somnifera extract treatment also resulted in reduced cell death in the model neuron TBI system. The cell death factor Bax was involved (its expression was reduced 2-fold by the treatment) and injury-induced reduction in neurite lengths and numbers was reversed by the treatment. This all indicates that W. somnifera root extract was neuroprotective and could have therapeutic potential to target factors involved in secondary injury and long-term sequelae of mild TBI.

Spatial variability of soil carbon and nitrogen in two hybrid poplar-hay crop systems in southern Quebec, Canada

NASA Astrophysics Data System (ADS)

Winans, K. S.

2013-12-01

Canadian agricultural operations contribute approximately 8% of national GHG emissions each year, mainly from fertilizers, enteric fermentation, and manure management (Environment Canada, 2010). With improved management of cropland and forests, it is possible to mitigate GHG emissions through carbon (C) sequestration while enhancing soil and crop productivity. Tree-based intercropped (TBI) systems, consisting of a fast-growing woody species such as poplar (Populus spp.) planted in widely-spaced rows with crops cultivated between tree rows, were one of the technologies prioritized for investigation by the Agreement for the Agricultural Greenhouse Gases Program (AAGGP), because fast growing trees can be a sink for atmospheric carbon-dioxide (CO2) as well as a long-term source of farm income (Montagnini and Nair, 2004). However, there are relatively few estimates of the C sequestration in the trees or due to tree inputs (e.g., fine root turnover, litterfall that gets incorporated into SOC), and hybrid poplars grow exponentially in the first 8-10 years after planting. With the current study, our objectives were (1) to evaluate spatial variation in soil C and nitrogen (N) storage, CO2 and nitrogen oxide (N20), and tree and crop productivity for two hybrid poplar-hay intercrop systems at year 9, comparing TBI vs. non-TBI systems, and (2) to evaluate TBI systems in the current context of C trading markets, which value C sequestration in trees, unharvested crop components, and soils of TBI systems. The study results will provide meaningful measures that indicate changes due to TBI systems in the short-term and in the long-term, in terms of GHG mitigation, enhanced soil and crop productivity, as well as the expected economic returns in TBI systems.

Neuropsychiatric Symptom Modeling in Male and Female C57BL/6J Mice after Experimental Traumatic Brain Injury

PubMed Central

Tucker, Laura B.; Burke, John F.; Fu, Amanda H.

2017-01-01

Abstract Psychiatric symptoms such as anxiety and depression are frequent and persistent complaints following traumatic brain injury (TBI). Modeling these symptoms in animal models of TBI affords the opportunity to determine mechanisms underlying behavioral pathologies and to test potential therapeutic agents. However, testing these symptoms in animal models of TBI has yielded inconsistent results. The goal of the current study was to employ a battery of tests to measure multiple anxiety- and depressive-like symptoms following TBI in C57BL/6J mice, and to determine if male and female mice are differentially affected by the injury. Following controlled cortical impact (CCI) at a parietal location, neither male nor female mice showed depressive-like symptoms as measured by the Porsolt forced-swim test and sucrose preference test. Conclusions regarding anxiety-like behaviors were dependent upon the assay employed; CCI-induced thigmotaxis in the open field suggested an anxiogenic effect of the injury; however, results from the elevated zero maze, light-dark box, and marble-burying tests indicated that CCI reduced anxiety-like behaviors. Fewer anxiety-like behaviors were also associated with the female sex. Increased levels of activity were also measured in female mice and injured mice in these tests, and conclusions regarding anxiety should be taken with caution when experimental manipulations induce changes in baseline activity. These results underscore the irreconcilability of results from studies attempting to model TBI-induced neuropsychiatric symptoms. Changes in injury models or better attempts to replicate the clinical syndrome may improve the translational applicability of rodent models of TBI-induced anxiety and depression. PMID:27149139

TH-EF-BRB-06: Implementation of a Modulated-Arc Total Body Irradiation (TBI) Technique Using the RayStation Treatment Planning System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Phillips, J; Cheung, J; Held, M

2016-06-15

Purpose: To develop a clinical workflow for delivering a modulated-arc total body irradiation (TBI) with RayStation scripting. This technique uses arc fields with the patient lying at floor level on a padded table and is validated through measurements taken on a custom-made TBI phantom. Methods: Treatment planning was performed for a retrospective cohort of eight patients with a diverse range of heights and body types. Each was replanned using an open-field dual arc method, with the patient in supine and prone positions on the floor of the vault. All plans were optimized using Raystation Planning 4.7.2.5 (RaySearch Laboratories, Stockholm, Sweden),more » with 200 cGy prescribed to the 95% of the body contour − 5mm. This results in an open-field beam that sweeps craniocaudally across the length of the patient. The technique is validated with measurements at 10 cm intervals in a custom-milled, 5 cm thick acrylic phantom. A centrally located CC13 ion chamber and a Mobile MOSFET (Best Medical Canada, Ottawa, ON) detector array were used to measure dose. Supine and prone arcs for each patient were consecutively delivered, and the aggregate dose at each point was compared to the planned dose calculated in the phantom. Results: The ion chamber measurements differed from the planned dose by an average of .5%, with a standard deviation of 2.1%. All measured data for the MOSFETS were within 10% of the corresponding planned dose except for two outlying points. The standard deviation of dose differences across the entire cohort was 4.0%. Most significant discrepancies occurred either in inhomogeneous regions with large gradients, or at inferior points where beam angle was steepest. Conclusion: We have confirmed that the planned dose is well matched to our measurements within 10% for this method of planning and delivery. We are currently incorporating this technique into our clinical workflow. This work is supported by RaySearch.« less

Inhibition of activated NR2B gene- and caspase-3 protein-expression by glutathione following traumatic brain injury in a rat model

PubMed Central

Arifin, Muhammad Zafrullah; Faried, Ahmad; Shahib, Muhammad Nurhalim; Wiriadisastra, Kahdar; Bisri, Tatang

2011-01-01

Background. Traumatic brain injury (TBI) remains a major cause of death and disability. Oxidative stress is an important element of the injury cascade following TBI. Progressive compromise of antioxidant defenses and free radical-mediated lipid peroxidation are one of the major mechanisms of secondary TBI. NR2B is a glutamate receptor and its activation is caused by TBI increasing a brain cell death, along with caspase-3 as a hall mark of apoptosis. Glutathione is a potent free radical scavenger that might prevent secondary TBI damage and inhibited apoptosis. Materials and Methods. In the present study, it aims to demonstrate the effect of glutathione on inhibition of brain oxidative damage in a TBI rat model. Results. In this study, the expressions of mRNA NR2B in placebo group and groups with glutathione administration at 0, 3, and 6 hours after TBI were 328.14, 229.90, 178.50, and 136.14, respectively (P<0.001). The highest caspase-3 expression was shown in placebo group with 66.7% showing strong positive results (>80%); as expected, glutathione administered in 0, 3, and 6 hours groups had lower strong positive results of 50%, 16.7%, and 16.7%, respectively, (P=0.025). Conclusion. In conclusion, this study showed that glutathione administration in a TBI rat model decreased NR2B gene- and caspase-3 protein-expression that lead to the inhibition of brain cell death. Our results suggest that glutathione, as a potent free radical scavenger, has a brain cell protective effect against oxidative damage and cell death induced by TBI in rat model. PMID:22347327

Respiratory, physical, and psychological benefits of breath-focused yoga for adults with severe traumatic brain injury (TBI): a brief pilot study report.

PubMed

Silverthorne, Colin; Khalsa, Sat Bir S; Gueth, Robin; DeAvilla, Nicole; Pansini, Janie

2012-01-01

This pilot study was designed to identify the potential benefits of breath-focused yoga on respiratory, physical, and psychological functioning for adults with severe traumatic brain injury (TBI). Ten individuals with severe TBI who self-selected to attend weekly yoga classes and 4 no-treatment controls were evaluated. Participants were assessed at pretreatment baseline and at 3-month intervals for a total of 4 time points over 40 weeks. Outcomes of interest included observed exhale strength, ability to hold a breath or a tone, breathing rate, counted breaths (inhale and exhale), and heart rate, as well as self-reported physical and psycho-logical well-being. Repeated within-group analyses of variance revealed that the yoga group demonstrated significant longitudinal change on several measures of observed respiratory functioning and self-reported physical and psychological well-being over a 40-week period. Those in the control group showed marginal improvement on 2 of the 6 measures of respiratory health, physical and social functioning, emotional well-being, and general health. The small sample sizes precluded the analysis of between group differences. This study provides preliminary evidence that breath-focused yoga may improve respiratory functioning and self-perceived physical and psychological well-being of adults with severe TBI.

Prospective memory after moderate-to-severe traumatic brain injury: a multinomial modeling approach.

PubMed

Pavawalla, Shital P; Schmitter-Edgecombe, Maureen; Smith, Rebekah E

2012-01-01

Prospective memory (PM), which can be understood as the processes involved in realizing a delayed intention, is consistently found to be impaired after a traumatic brain injury (TBI). Although PM can be empirically dissociated from retrospective memory, it inherently involves both a prospective component (i.e., remembering that an action needs to be carried out) and retrospective components (i.e., remembering what action needs to be executed and when). This study utilized a multinomial processing tree model to disentangle the prospective (that) and retrospective recognition (when) components underlying PM after moderate-to-severe TBI. Seventeen participants with moderate to severe TBI and 17 age- and education-matched control participants completed an event-based PM task that was embedded within an ongoing computer-based color-matching task. The multinomial processing tree modeling approach revealed a significant group difference in the prospective component, indicating that the control participants allocated greater preparatory attentional resources to the PM task compared to the TBI participants. Participants in the TBI group were also found to be significantly more impaired than controls in the when aspect of the retrospective component. These findings indicated that the TBI participants had greater difficulty allocating the necessary preparatory attentional resources to the PM task and greater difficulty discriminating between PM targets and nontargets during task execution, despite demonstrating intact posttest recall and/or recognition of the PM tasks and targets.

The importance of structural anisotropy in computational models of traumatic brain injury.

PubMed

Carlsen, Rika W; Daphalapurkar, Nitin P

2015-01-01

Understanding the mechanisms of injury might prove useful in assisting the development of methods for the management and mitigation of traumatic brain injury (TBI). Computational head models can provide valuable insight into the multi-length-scale complexity associated with the primary nature of diffuse axonal injury. It involves understanding how the trauma to the head (at the centimeter length scale) translates to the white-matter tissue (at the millimeter length scale), and even further down to the axonal-length scale, where physical injury to axons (e.g., axon separation) may occur. However, to accurately represent the development of TBI, the biofidelity of these computational models is of utmost importance. There has been a focused effort to improve the biofidelity of computational models by including more sophisticated material definitions and implementing physiologically relevant measures of injury. This paper summarizes recent computational studies that have incorporated structural anisotropy in both the material definition of the white matter and the injury criterion as a means to improve the predictive capabilities of computational models for TBI. We discuss the role of structural anisotropy on both the mechanical response of the brain tissue and on the development of injury. We also outline future directions in the computational modeling of TBI.

Structural and Functional Alterations in Neocortical Circuits after Mild Traumatic Brain Injury

NASA Astrophysics Data System (ADS)

Vascak, Michal

National concern over traumatic brain injury (TBI) is growing rapidly. Recent focus is on mild TBI (mTBI), which is the most prevalent injury level in both civilian and military demographics. A preeminent sequelae of mTBI is cognitive network disruption. Advanced neuroimaging of mTBI victims supports this premise, revealing alterations in activation and structure-function of excitatory and inhibitory neuronal systems, which are essential for network processing. However, clinical neuroimaging cannot resolve the cellular and molecular substrates underlying such changes. Therefore, to understand the full scope of mTBI-induced alterations it is necessary to study cortical networks on the microscopic level, where neurons form local networks that are the fundamental computational modules supporting cognition. Recently, in a well-controlled animal model of mTBI, we demonstrated in the excitatory pyramidal neuron system, isolated diffuse axonal injury (DAI), in concert with electrophysiological abnormalities in nearby intact (non-DAI) neurons. These findings were consistent with altered axon initial segment (AIS) intrinsic activity functionally associated with structural plasticity, and/or disturbances in extrinsic systems related to parvalbumin (PV)-expressing interneurons that form GABAergic synapses along the pyramidal neuron perisomatic/AIS domains. The AIS and perisomatic GABAergic synapses are domains critical for regulating neuronal activity and E-I balance. In this dissertation, we focus on the neocortical excitatory pyramidal neuron/inhibitory PV+ interneuron local network following mTBI. Our central hypothesis is that mTBI disrupts neuronal network structure and function causing imbalance of excitatory and inhibitory systems. To address this hypothesis we exploited transgenic and cre/lox mouse models of mTBI, employing approaches that couple state-of-the-art bioimaging with electrophysiology to determine the structuralfunctional alterations of excitatory and

SU-C-213-04: Application of Depth Sensing and 3D-Printing Technique for Total Body Irradiation (TBI) Patient Measurement and Treatment Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, M; Suh, T; Research Institute of Biomedical Engineering, College of Medicine, The Catholic University of Korea, Seoul

2015-06-15

Purpose: To develop and validate an innovative method of using depth sensing cameras and 3D printing techniques for Total Body Irradiation (TBI) treatment planning and compensator fabrication. Methods: A tablet with motion tracking cameras and integrated depth sensing was used to scan a RANDOTM phantom arranged in a TBI treatment booth to detect and store the 3D surface in a point cloud (PC) format. The accuracy of the detected surface was evaluated by comparison to extracted measurements from CT scan images. The thickness, source to surface distance and off-axis distance of the phantom at different body section was measured formore » TBI treatment planning. A 2D map containing a detailed compensator design was calculated to achieve uniform dose distribution throughout the phantom. The compensator was fabricated using a 3D printer, silicone molding and tungsten powder. In vivo dosimetry measurements were performed using optically stimulated luminescent detectors (OSLDs). Results: The whole scan of the anthropomorphic phantom took approximately 30 seconds. The mean error for thickness measurements at each section of phantom compare to CT was 0.44 ± 0.268 cm. These errors resulted in approximately 2% dose error calculation and 0.4 mm tungsten thickness deviation for the compensator design. The accuracy of 3D compensator printing was within 0.2 mm. In vivo measurements for an end-to-end test showed the overall dose difference was within 3%. Conclusion: Motion cameras and depth sensing techniques proved to be an accurate and efficient tool for TBI patient measurement and treatment planning. 3D printing technique improved the efficiency and accuracy of the compensator production and ensured a more accurate treatment delivery.« less

Probing mechanobiology with laser-induced shockwaves

NASA Astrophysics Data System (ADS)

Carmona, Christopher; Preece, Daryl C.; Gomez-Godinez, Veronica; Shi, Linda Z.; Berns, Michael W.

2017-08-01

Traumatic Brain Injury (TBI) occurs when an external force injures the brain. While clinical outcomes of TBI can vary widely in severity, few mechanisms of neurodegeneration following TBI have been identified for treatment. We propose a model for studying TBI using laser-induced shockwaves (LISs). An optical system was developed that allows single cells to be studied in response to LISs. Our system utilizes an optically-coupled force measurement component that allows for the visualization of shockwave dynamics. Here, the force measurement system is characterized by imaging stages over the period of violent expansion and collapse of microbubbles responsible for shockwave generation.

Diagnosing Contributions of Sensory and Cognitive Deficits to Hearing Dysfunction in Blast Exposed/TBI Service Members

DTIC Science & Technology

2016-10-01

1 AWARD NUMBER: W81XWH-15-1-0490 TITLE: Diagnosing Contributions of Sensory and Cognitive Deficits to Hearing Dysfunction in Blast-Exposed/ TBI...3. DATES COVERED 15 Sep 2015 - 14 Sep 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Diagnosing Contributions of Sensory and Cognitive Deficits to...installed at WRNMMC, and is running finalized versions of both the auditory and visual selective attention tasks. Subject recruitment has started, and

Neurobehavioral, neuropathological and biochemical profiles in a novel mouse model of co-morbid post-traumatic stress disorder and mild traumatic brain injury

PubMed Central

Ojo, Joseph O.; Greenberg, M. Banks; Leary, Paige; Mouzon, Benoit; Bachmeier, Corbin; Mullan, Michael; Diamond, David M.; Crawford, Fiona

2014-01-01

Co-morbid mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD) has become the signature disorder for returning combat veterans. The clinical heterogeneity and overlapping symptomatology of mTBI and PTSD underscore the need to develop a preclinical model that will enable the characterization of unique and overlapping features and allow discrimination between both disorders. This study details the development and implementation of a novel experimental paradigm for PTSD and combined PTSD-mTBI. The PTSD paradigm involved exposure to a danger-related predator odor under repeated restraint over a 21 day period and a physical trauma (inescapable footshock). We administered this paradigm alone, or in combination with a previously established mTBI model. We report outcomes of behavioral, pathological and biochemical profiles at an acute timepoint. PTSD animals demonstrated recall of traumatic memories, anxiety and an impaired social behavior. In both mTBI and combination groups there was a pattern of disinhibitory like behavior. mTBI abrogated both contextual fear and impairments in social behavior seen in PTSD animals. No major impairment in spatial memory was observed in any group. Examination of neuroendocrine and neuroimmune responses in plasma revealed a trend toward increase in corticosterone in PTSD and combination groups, and an apparent increase in Th1 and Th17 proinflammatory cytokine(s) in the PTSD only and mTBI only groups respectively. In the brain there were no gross neuropathological changes in any groups. We observed that mTBI on a background of repeated trauma exposure resulted in an augmentation of axonal injury and inflammatory markers, neurofilament L and ICAM-1 respectively. Our observations thus far suggest that this novel stress-trauma-related paradigm may be a useful model for investigating further the overlapping and distinct spatio-temporal and behavioral/biochemical relationship between mTBI and PTSD experienced by combat

Docosahexaenoic Acid (DHA) Provides Neuroprotection in Traumatic Brain Injury Models via Activating Nrf2-ARE Signaling.

PubMed

Zhu, Wei; Ding, Yuexia; Kong, Wei; Li, Tuo; Chen, Hongguang

2018-04-16

In this study, we explored the neuroprotective effects of docosahexaenoic acid (DHA) in traumatic brain injury (TBI) models. In this study, we first confirmed that DHA was neuroprotective against TBI via the NSS test and Morris water maze experiment. Western blot was conducted to identify the expression of Bax, caspase-3, and Bcl-2. And the cell apoptosis of the TBI models was validated by TUNEL staining. Relationships between nuclear factor erythroid 2-related factor 2-antioxidant response element (Nrf2-ARE) pathway-related genes and DHA were explored by RT-PCR and Western blot. Rats of the DHA group performed remarkably better than those of the TBI group in both NSS test and water maze experiment. DHA conspicuously promoted the expression of Bcl-2 and diminished that of cleaved caspase-3 and Bax, indicating the anti-apoptotic role of DHA. Superoxide dismutase (SOD) activity and cortical malondialdehyde content, glutathione peroxidase (GPx) activity were renovated in rats receiving DHA treatment, implying that the neuroprotective influence of DHA was derived from lightening the oxidative stress caused by TBI. Moreover, immunofluorescence and Western blot experiments revealed that DHA facilitated the translocation of Nrf2 to the nucleus. DHA administration also notably increased the expression of the downstream factors NAD(P)H:quinone oxidoreductase (NQO-1) and heme oxygenase 1(HO-1). DHA exerted neuroprotective influence on the TBI models, potentially through activating the Nrf2- ARE pathway.

Influence of Post-Traumatic Stress Disorder on Neuroinflammation and Cell Proliferation in a Rat Model of Traumatic Brain Injury

PubMed Central

Diamond, David M.; Shinozuka, Kazutaka; Ishikawa, Hiroto; Hernandez, Diana G.; Sanberg, Paul R.; Kaneko, Yuji; Borlongan, Cesar V.

2013-01-01

Long-term consequences of traumatic brain injury (TBI) are closely associated with the development of severe psychiatric disorders, such as post-traumatic stress disorder (PTSD), yet preclinical studies on pathological changes after combined TBI with PTSD are lacking. In the present in vivo study, we assessed chronic neuroinflammation, neuronal cell loss, cell proliferation and neuronal differentiation in specific brain regions of adult Sprague-Dawley male rats following controlled cortical impact model of moderate TBI with or without exposure to PTSD. Eight weeks post-TBI, stereology-based histological analyses revealed no significant differences between sham and PTSD alone treatment across all brain regions examined, whereas significant exacerbation of OX6-positive activated microglial cells in the striatum, thalamus, and cerebral peduncle, but not cerebellum, in animals that received TBI alone and combined TBI-PTSD compared with PTSD alone and sham treatment. Additional immunohistochemical results revealed a significant loss of CA3 pyramidal neurons in the hippocampus of TBI alone and TBI-PTSD compared to PTSD alone and sham treatment. Further examination of neurogenic niches revealed a significant downregulation of Ki67-positive proliferating cells, but not DCX-positive neuronally migrating cells in the neurogenic subgranular zone and subventricular zone for both TBI alone and TBI-PTSD compared to PTSD alone and sham treatment. Comparisons of levels of neuroinflammation and neurogenesis between TBI alone and TBI+PTSD revealed that PTSD did not exacerbate the neuropathological hallmarks of TBI. These results indicate a progressive deterioration of the TBI brain, which, under the conditions of the present approach, was not intensified by PTSD, at least within our time window and within the examined areas of the brain. Although the PTSD manipulation employed here did not exacerbate the pathological effects of TBI, the observed long-term inflammation and suppressed

Systems biomarkers as acute diagnostics and chronic monitoring tools for traumatic brain injury

NASA Astrophysics Data System (ADS)

Wang, Kevin K. W.; Moghieb, Ahmed; Yang, Zhihui; Zhang, Zhiqun

2013-05-01

Traumatic brain injury (TBI) is a significant biomedical problem among military personnel and civilians. There exists an urgent need to develop and refine biological measures of acute brain injury and chronic recovery after brain injury. Such measures "biomarkers" can assist clinicians in helping to define and refine the recovery process and developing treatment paradigms for the acutely injured to reduce secondary injury processes. Recent biomarker studies in the acute phase of TBI have highlighted the importance and feasibilities of identifying clinically useful biomarkers. However, much less is known about the subacute and chronic phases of TBI. We propose here that for a complex biological problem such as TBI, multiple biomarker types might be needed to harness the wide range of pathological and systemic perturbations following injuries, including acute neuronal death, neuroinflammation, neurodegeneration and neuroregeneration to systemic responses. In terms of biomarker types, they range from brain-specific proteins, microRNA, genetic polymorphism, inflammatory cytokines and autoimmune markers and neuro-endocrine hormones. Furthermore, systems biology-driven biomarkers integration can help present a holistic approach to understanding scenarios and complexity pathways involved in brain injury.

Emerging Science in TBI Care: Diagnosis and Treatment: The Quadruple Aim: Learning & Growth, Readiness, Experience of Care

DTIC Science & Technology

2011-01-25

Behavioral problems – Emotional problems – “Unexplained“ symptoms TBI-related impairments increase vulnerability to subsequent injury until full...developed specific protocols for management of concussed Service members and those with recurrent concussion  Transition from symptom driven reporting...with early treatment.  VISION: Every Warfighter trained to: – Recognize the signs/ symptoms – Equipped to reduce the effects And in the event of an

Wake-promoting actions of median nerve stimulation in TBI-induced coma: An investigation of orexin-A and orexin receptor 1 in the hypothalamic region.

PubMed

Zhong, Ying-Jun; Feng, Zhen; Wang, Liang; Wei, Tian-Qi

2015-09-01

A coma is a serious complication, which can occur following traumatic brain injury (TBI), for which no effective treatment has been established. Previous studies have suggested that neural electrical stimulation, including median nerve stimulation (MNS), may be an effective method for treating patients in a coma, and orexin‑A, an excitatory hypothalamic neuropeptide, may be involved in wakefulness. However, the exact mechanisms underlying this involvement remain to be elucidated. The present study aimed to examine the arousal‑promoting role of MNS in rats in a TBI‑induced coma and to investigate the potential mechanisms involved. A total of 90 rats were divided into three groups, comprising a control group, sham‑stimulated (TBI) group and a stimulated (TBI + MNS) group. MNS was performed on the animals, which were in a TBI‑induced comatose state. Changes in the behavior of the rats were observed following MNS. Subsequently, hypothalamic tissues were extracted from the rats 6, 12 and 24 h following TBI or MNS, respectively. The expression levels of orexin‑A and orexin receptor‑1 (OX1R) in the hypothalamus were examined using immunohistochemistry, western blotting and an enzyme‑linked immunosorbent assay. The results demonstrated that 21 rats subjected to TBI‑induced coma exhibited a restored righting reflex and response to pain stimuli following MNS. In addition, ignificant differences in the expression levels of orexin‑A and OXIR were observed among the three groups and among the time‑points. Orexin‑A and OX1R were upregulated following MNS. The rats in the stimulated group reacted to the MNS and exhibited a re‑awakening response. The results of the present study indicated that MNS may be a therapeutic option for TBI‑induced coma. The mechanism may be associated with increasing expression levels of the excitatory hypothalamic neuropeptide, orexin-A, and its receptor, OX1R, in the hypothalamic region.

Effect Size as the Essential Statistic in Developing Methods for mTBI Diagnosis.

PubMed

Gibson, Douglas Brandt

2015-01-01

The descriptive statistic known as "effect size" measures the distinguishability of two sets of data. Distingishability is at the core of diagnosis. This article is intended to point out the importance of effect size in the development of effective diagnostics for mild traumatic brain injury and to point out the applicability of the effect size statistic in comparing diagnostic efficiency across the main proposed TBI diagnostic methods: psychological, physiological, biochemical, and radiologic. Comparing diagnostic approaches is difficult because different researcher in different fields have different approaches to measuring efficacy. Converting diverse measures to effect sizes, as is done in meta-analysis, is a relatively easy way to make studies comparable.

Using Xbox kinect motion capture technology to improve clinical rehabilitation outcomes for balance and cardiovascular health in an individual with chronic TBI.

PubMed

Chanpimol, Shane; Seamon, Bryant; Hernandez, Haniel; Harris-Love, Michael; Blackman, Marc R

2017-01-01

Motion capture virtual reality-based rehabilitation has become more common. However, therapists face challenges to the implementation of virtual reality (VR) in clinical settings. Use of motion capture technology such as the Xbox Kinect may provide a useful rehabilitation tool for the treatment of postural instability and cardiovascular deconditioning in individuals with chronic severe traumatic brain injury (TBI). The primary purpose of this study was to evaluate the effects of a Kinect-based VR intervention using commercially available motion capture games on balance outcomes for an individual with chronic TBI. The secondary purpose was to assess the feasibility of this intervention for eliciting cardiovascular adaptations. A single system experimental design ( n = 1) was utilized, which included baseline, intervention, and retention phases. Repeated measures were used to evaluate the effects of an 8-week supervised exercise intervention using two Xbox One Kinect games. Balance was characterized using the dynamic gait index (DGI), functional reach test (FRT), and Limits of Stability (LOS) test on the NeuroCom Balance Master. The LOS assesses end-point excursion (EPE), maximal excursion (MXE), and directional control (DCL) during weight-shifting tasks. Cardiovascular and activity measures were characterized by heart rate at the end of exercise (HRe), total gameplay time (TAT), and time spent in a therapeutic heart rate (TTR) during the Kinect intervention. Chi-square and ANOVA testing were used to analyze the data. Dynamic balance, characterized by the DGI, increased during the intervention phase χ 2 (1, N = 12) = 12, p = .001. Static balance, characterized by the FRT showed no significant changes. The EPE increased during the intervention phase in the backward direction χ 2 (1, N = 12) = 5.6, p = .02, and notable improvements of DCL were demonstrated in all directions. HRe ( F (2,174) = 29.65, p = < .001) and time in a TTR ( F (2, 12) = 4.19, p = .04) decreased

Deficient pain modulatory systems in patients with mild traumatic brain and chronic post-traumatic headache: implications for its mechanism.

PubMed

Defrin, Ruth; Riabinin, Miri; Feingold, Yelena; Schreiber, Shaul; Pick, Chaim G

2015-01-01

Although the prevalence rate of chronic post-traumatic headache (CPTHA) after mild traumatic brain injury (TBI) reaches up to 95%, its mechanism is unknown, and little is known about the characteristics of the pain system in this condition. Our aim was to investigate the capabilities of two pain modulatory systems among individuals with CPTHA and study their association with CPTHA, here for the first time. Forty-six subjects participated; 16 with TBI and CPTHA, 12 with TBI without CPTHA, and 18 healthy controls. Testing included the measurement of heat-pain (HPT) and pressure-pain (PPT) thresholds in the forehead and forearm, pain adaptation to tonic noxious heat, and conditioned pain modulation (CPM).The participants completed a post-traumatic stress disorder (PTSD) questionnaire. The two TBI groups did not differ in the TBI and background characteristics. However, TBI patients with CPTHA had significantly higher HPT and lower PPT in the cranium and higher PTSD symptomatology than TBI patients without CPTHA and healthy controls. Adaptation to pain and CPM were diminished in the CPTHA group compared with the two control groups. The intensity of CPTHA correlated negatively with cranial PPT, magnitude of pain adaptation, and CPM. CPTHA intensity correlated positively with PTSD symptomatology. CPTHA appears to be characterized by cranial hyperalgesia and dysfunctional pain modulation capabilities, which are associated with CPTHA magnitude. It is concluded that damage to pain modulatory systems along with chronic cranial sensitization underlies the development of CPTHA. PTSD may reinforce CPTHA and vice versa. Clinical implications are discussed.

Deficient Pain Modulatory Systems in Patients with Mild Traumatic Brain and Chronic Post-Traumatic Headache: Implications for its Mechanism

PubMed Central

Riabinin, Miri; Feingold, Yelena; Schreiber, Shaul; Pick, Chaim G.

2015-01-01

Abstract Although the prevalence rate of chronic post-traumatic headache (CPTHA) after mild traumatic brain injury (TBI) reaches up to 95%, its mechanism is unknown, and little is known about the characteristics of the pain system in this condition. Our aim was to investigate the capabilities of two pain modulatory systems among individuals with CPTHA and study their association with CPTHA, here for the first time. Forty-six subjects participated; 16 with TBI and CPTHA, 12 with TBI without CPTHA, and 18 healthy controls. Testing included the measurement of heat-pain (HPT) and pressure-pain (PPT) thresholds in the forehead and forearm, pain adaptation to tonic noxious heat, and conditioned pain modulation (CPM).The participants completed a post-traumatic stress disorder (PTSD) questionnaire. The two TBI groups did not differ in the TBI and background characteristics. However, TBI patients with CPTHA had significantly higher HPT and lower PPT in the cranium and higher PTSD symptomatology than TBI patients without CPTHA and healthy controls. Adaptation to pain and CPM were diminished in the CPTHA group compared with the two control groups. The intensity of CPTHA correlated negatively with cranial PPT, magnitude of pain adaptation, and CPM. CPTHA intensity correlated positively with PTSD symptomatology. CPTHA appears to be characterized by cranial hyperalgesia and dysfunctional pain modulation capabilities, which are associated with CPTHA magnitude. It is concluded that damage to pain modulatory systems along with chronic cranial sensitization underlies the development of CPTHA. PTSD may reinforce CPTHA and vice versa. Clinical implications are discussed. PMID:25068510

Finite element modeling of human brain response to football helmet impacts.

PubMed

Darling, T; Muthuswamy, J; Rajan, S D

2016-10-01

The football helmet is used to help mitigate the occurrence of impact-related traumatic (TBI) and minor traumatic brain injuries (mTBI) in the game of American football. While the current helmet design methodology may be adequate for reducing linear acceleration of the head and minimizing TBI, it however has had less effect in minimizing mTBI. The objectives of this study are (a) to develop and validate a coupled finite element (FE) model of a football helmet and the human body, and (b) to assess responses of different regions of the brain to two different impact conditions - frontal oblique and crown impact conditions. The FE helmet model was validated using experimental results of drop tests. Subsequently, the integrated helmet-human body FE model was used to assess the responses of different regions of the brain to impact loads. Strain-rate, strain, and stress measures in the corpus callosum, midbrain, and brain stem were assessed. Results show that maximum strain-rates of 27 and 19 s(-1) are observed in the brain-stem and mid-brain, respectively. This could potentially lead to axonal injuries and neuronal cell death during crown impact conditions. The developed experimental-numerical framework can be used in the study of other helmet-related impact conditions.

Community-integrated brain injury rehabilitation: Treatment models and challenges for civilian, military, and veteran populations.

PubMed

Trudel, Tina M; Nidiffer, F Don; Barth, Jeffrey T

2007-01-01

Traumatic brain injury (TBI) is a major health problem in civilian, military, and veteran populations. Individuals experiencing moderate to severe TBI require a continuum of care involving acute hospitalization and postacute rehabilitation, including community reintegration and, one would hope, a return home to function as a productive member of the community. In the military, the goal is to help individuals with TBI return to active duty or make an optimal return to civilian life if the extent of their injuries necessitates a "medical board" discharge. Whether civilian, military, or veteran with TBI, individuals who move beyond the need to live in a facility must be reintegrated back into the community. This article discusses four treatment models for community reintegration, reviews treatment standardization and outcome issues, and describes a manualized rehabilitation pilot program designed to provide community reintegration and return to duty/work for civilians, veterans, and military personnel with TBI.

Is aura around citicoline fading? A systemic review

PubMed Central

Agarwal, Saurabh; Patel, Bhoomika M.

2017-01-01

Stroke and traumatic brain injury (TBI) are the critical public health and socioeconomic problems throughout the world. At present, citicoline is used as a coadjuvant for the management of acute ischemic stroke (AIS) and TBI in various countries. This systemic review analyzes the beneficial role of citicoline in AIS and TBI. This systemic review is based on “PubMed” and “Science Direct” search results for citicoline role in stroke and TBI. In this systemic review, we included 12 human trials. A meta-analysis was performed on the basis of neurological evaluation, functional evaluation and Glasgow outcome scale, domestic adaptation evaluation outcomes, and cognitive outcome individually. In neurological evaluation, domestic adaptation evaluation, and cognitive outcomes, there was no significant difference in both the citicoline and placebo groups (odds ratio [OR] = 1.04 [0.9–1.2, P = 0.583]; OR = 1.1 [0.94–1.27, P = 0.209]; OR = 0.953 [0.75–1.2, P = 0.691]). In evaluation of functional outcomes, there was significant difference in both groups and OR was 1.18 (1.04–1.34, P = 0.01). Functional outcomes were significantly improved by citicoline, but the positive role of this drug in neurological recovery, domestic adaptation, and cognitive outcomes is still a topic of discussion for future. PMID:28458415

Evaluating a Novel Sleep-Focused Mind-Body Rehabilitative Program for Veterans with mTBI and Other Polytrauma Symptoms: An RCT Study

DTIC Science & Technology

2015-09-01

mindfulness, insomnia , sleep disturbance, mild Traumatic Brain Injury (mTBI), OEF/OIF 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT...explore underlying mechanisms of action involved in treatment benefits resulting from MBB and SED by using both a biomarker of stress and a

Systematic review and meta-analysis of efficacy of mesenchymal stem cells on locomotor recovery in animal models of traumatic brain injury.

PubMed

Peng, Weijun; Sun, Jing; Sheng, Chenxia; Wang, Zhe; Wang, Yang; Zhang, Chunhu; Fan, Rong

2015-03-26

The therapeutic potential of mesenchymal stem cells (MSCs) for traumatic brain injury (TBI) is attractive. Conducting systematic review and meta-analyses based on data from animal studies can be used to inform clinical trial design. To conduct a systematic review and meta-analysis to (i) systematically review the literatures describing the effect of MSCs therapy in animal models of TBI, (ii) determine the estimated effect size of functional locomotor recovery after experimental TBI, and (iii) to provide empirical evidence of biological factors associated with greater efficacy. We conducted a systematic search of PubMed, EMBASE, and Web of Science and hand searched related references. Studies were selected if they reported the efficacy of MSCs in animal models of TBI. Two investigators independently assessed the identified studies. We extracted the details of individual study characteristics from each publication, assessed study quality, evaluated the effect sizes of MSCs treatment, and performed stratified meta-analysis and meta-regression, to assess the influence of study design on the estimated effect size. The presence of small effect sizes was investigated using funnel plots and Egger's tests. Twenty-eight eligible controlled studies were identified. The study quality was modest. Between-study heterogeneity was large. Meta-analysis showed that MSCs exert statistically significant positive effects on sensorimotor and neurological motor function. For sensorimotor function, maximum effect size in studies with a quality score of 5 was found in the weight-drop impact injury TBI model established in male SD rats, to which syngeneic umbilical cord-derived MSCs intracerebrally at cell dose of (1-5)×10(6) was administered r 6 hours following TBI, using ketamine as anesthetic agent. For neurological motor function, effect size was maximum for studies with a quality score of 5, in which the weight-drop impact injury TBI models of the female Wistar rats were adopted, with

Biomarkers of Traumatic Injury Are Transported from Brain to Blood via the Glymphatic System

PubMed Central

Plog, Benjamin A.; Dashnaw, Matthew L.; Hitomi, Emi; Peng, Weiguo; Liao, Yonghong; Lou, Nanhong; Deane, Rashid

2015-01-01

The nonspecific and variable presentation of traumatic brain injury (TBI) has motivated an intense search for blood-based biomarkers that can objectively predict the severity of injury. However, it is not known how cytosolic proteins released from traumatized brain tissue reach the peripheral blood. Here we show in a murine TBI model that CSF movement through the recently characterized glymphatic pathway transports biomarkers to blood via the cervical lymphatics. Clinically relevant manipulation of glymphatic activity, including sleep deprivation and cisternotomy, suppressed or eliminated TBI-induced increases in serum S100β, GFAP, and neuron specific enolase. We conclude that routine TBI patient management may limit the clinical utility of blood-based biomarkers because their brain-to-blood transport depends on glymphatic activity. PMID:25589747

A peptide for targeted, systemic delivery of imaging and therapeutic compounds into acute brain injuries

NASA Astrophysics Data System (ADS)

Mann, Aman P.; Scodeller, Pablo; Hussain, Sazid; Joo, Jinmyoung; Kwon, Ester; Braun, Gary B.; Mölder, Tarmo; She, Zhi-Gang; Kotamraju, Venkata Ramana; Ranscht, Barbara; Krajewski, Stan; Teesalu, Tambet; Bhatia, Sangeeta; Sailor, Michael J.; Ruoslahti, Erkki

2016-06-01

Traumatic brain injury (TBI) is a major health and socio-economic problem, but no pharmacological agent is currently approved for the treatment of acute TBI. Thus, there is a great need for advances in this field. Here, we describe a short peptide (sequence CAQK) identified by in vivo phage display screening in mice with acute brain injury. The CAQK peptide selectively binds to injured mouse and human brain, and systemically injected CAQK specifically homes to sites of brain injury in mouse models. The CAQK target is a proteoglycan complex upregulated in brain injuries. Coupling to CAQK increased injury site accumulation of systemically administered molecules ranging from a drug-sized molecule to nanoparticles. CAQK-coated nanoparticles containing silencing oligonucleotides provided the first evidence of gene silencing in injured brain parenchyma by systemically administered siRNA. These findings present an effective targeting strategy for the delivery of therapeutics in clinical management of acute brain injuries.

Traumatic brain injury caused by laser-induced shock wave in rats: a novel laboratory model for studying blast-induced traumatic brain injury

NASA Astrophysics Data System (ADS)

Hatano, Ben; Matsumoto, Yoshihisa; Otani, Naoki; Saitoh, Daizoh; Tokuno, Shinichi; Satoh, Yasushi; Nawashiro, Hiroshi; Matsushita, Yoshitaro; Sato, Shunichi

2011-03-01

The detailed mechanism of blast-induced traumatic brain injury (bTBI) has not been revealed yet. Thus, reliable laboratory animal models for bTBI are needed to investigate the possible diagnosis and treatment for bTBI. In this study, we used laser-induced shock wave (LISW) to induce TBI in rats and investigated the histopathological similarities to actual bTBI. After craniotomy, the rat brain was exposed to a single shot of LISW with a diameter of 3 mm at various laser fluences. At 24 h after LISW exposure, perfusion fixation was performed and the extracted brain was sectioned; the sections were stained with hematoxylin-eosin. Evans blue (EB) staining was also used to evaluate disruption of the blood brain barrier. At certain laser fluence levels, neural cell injury and hemorrhagic lesions were observed in the cortex and subcortical region. However, injury was limited in the tissue region that interacted with the LISW. The severity of injury increased with increasing laser fluence and hence peak pressure of the LISW. Fluorescence originating from EB was diffusively observed in the injuries at high fluence levels. Due to the grade and spatial controllability of injuries and the histological observations similar to those in actual bTBI, brain injuries caused by LISWs would be useful models to study bTBI.

Moderate Traumatic Brain Injury: Clinical Characteristics and a Prognostic Model of 12-Month Outcome.

PubMed

Einarsen, Cathrine Elisabeth; van der Naalt, Joukje; Jacobs, Bram; Follestad, Turid; Moen, Kent Gøran; Vik, Anne; Håberg, Asta Kristine; Skandsen, Toril

2018-06-01

Patients with moderate traumatic brain injury (TBI) often are studied together with patients with severe TBI, even though the expected outcome of the former is better. Therefore, we aimed to describe patient characteristics and 12-month outcomes, and to develop a prognostic model based on admission data, specifically for patients with moderate TBI. Patients with Glasgow Coma Scale scores of 9-13 and age ≥16 years were prospectively enrolled in 2 level I trauma centers in Europe. Glasgow Outcome Scale Extended (GOSE) score was assessed at 12 months. A prognostic model predicting moderate disability or worse (GOSE score ≤6), as opposed to a good recovery, was fitted by penalized regression. Model performance was evaluated by area under the curve of the receiver operating characteristics curves. Of the 395 enrolled patients, 81% had intracranial lesions on head computed tomography, and 71% were admitted to an intensive care unit. At 12 months, 44% were moderately disabled or worse (GOSE score ≤6), whereas 8% were severely disabled and 6% died (GOSE score ≤4). Older age, lower Glasgow Coma Scale score, no day-of-injury alcohol intoxication, presence of a subdural hematoma, occurrence of hypoxia and/or hypotension, and preinjury disability were significant predictors of GOSE score ≤6 (area under the curve = 0.80). Patients with moderate TBI exhibit characteristics of significant brain injury. Although few patients died or experienced severe disability, 44% did not experience good recovery, indicating that follow-up is needed. The model is a first step in development of prognostic models for moderate TBI that are valid across centers. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

The influence of crystalline electrical field on magnetic and magnetocaloric properties in Er1-yTbyAl2 compounds

NASA Astrophysics Data System (ADS)

Ribeiro, P. O.; Alho, B. P.; Alvarenga, T. S. T.; Nóbrega, E. P.; de Sousa, V. S. R.; Carvalho, A. Magnus G.; Caldas, A.; Lopes, P. H. O.; von Ranke, P. J.

2017-11-01

We report the anisotropy of magnetic field-induced entropy change in rare earth Er1-yTbyAl2 compounds (y = 0.00, 0.25, 0.50, 0.75 and 1.00). In the present work, we use a model Hamiltonian that includes the crystalline electrical field anisotropy in both Er and Tb magnetic sublattices, chemical disorder in exchange interactions among Er-Er, Tb-Tb and Er-Tb magnetic ions and the Zeeman effect. We investigated the isothermal magnetic entropy change ΔST for a magnetic field of 1 T rotating from a hard 〈0 0 1〉 to the easy 〈1 1 1〉 direction. We also performed a systematic analysis of the reorientation temperature as a function of the magnetic field intensity. The anisotropic magnetocaloric effect highlights the applicability of this effect on the rotating magnetic refrigeration.

Neurodegeneration and Sensorimotor Deficits in the Mouse Model of Traumatic Brain Injury

PubMed Central

Bhowmick, Saurav; D‘Mello, Veera; Ponery, Nizmi; Abdul-Muneer, P. M.

2018-01-01

Traumatic brain injury (TBI) can result in persistent sensorimotor and cognitive deficits, which occur through a cascade of deleterious pathophysiological events over time. In this study, we investigated the hypothesis that neurodegeneration caused by TBI leads to impairments in sensorimotor function. TBI induces the activation of the caspase-3 enzyme, which triggers cell apoptosis in an in vivo model of fluid percussion injury (FPI). We analyzed caspase-3 mediated apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and poly (ADP-ribose) polymerase (PARP) and annexin V western blotting. We correlated the neurodegeneration with sensorimotor deficits by conducting the animal behavioral tests including grid walk, balance beam, the inverted screen test, and the climb test. Our study demonstrated that the excess cell death or neurodegeneration correlated with the neuronal dysfunction and sensorimotor impairments associated with TBI. PMID:29316623

A mouse model of human repetitive mild traumatic brain injury

PubMed Central

Kane, Michael J.; Pérez, Mariana Angoa; Briggs, Denise I.; Viano, David C.; Kreipke, Christian W.; Kuhn, Donald M.

2011-01-01

A novel method for the study of repetitive mild traumatic brain injury (rmTBI) that models the most common form of head injury in humans is presented. Existing animal models of TBI impart focal, severe damage unlike that seen in repeated and mild concussive injuries, and few are configured for repetitive application. Our model is a modification of the Marmarou weight drop method and allows repeated head impacts to lightly anesthetized mice. A key facet of this method is the delivery of an impact to the cranium of an unrestrained subject allowing rapid acceleration of the free-moving head and torso, an essential characteristic known to be important for concussive injury in humans, and a factor that is missing from existing animal models of TBI. Our method does not require scalp incision, emplacement of protective skull helmets or surgery and the procedure can be completed in 1-2 minutes. Mice spontaneously recover the righting reflex and show no evidence of seizures, paralysis or impaired behavior. Skull fractures and intracranial bleeding are very rare. Minor deficits in motor coordination and locomotor hyperactivity recover over time. Histological analyses reveal mild astrocytic reactivity (increased expression of GFAP) and increased phospho-tau but a lack of blood-brain-barrier disruption, edema and microglial activation. This new animal model is simple and cost-effective and will facilitate characterization of the neurobiological and behavioral consequences of rmTBI. It is also ideal for high throughput screening of potential new therapies for mild concussive injuries as experienced by athletes and military personnel. PMID:21930157

Characteristics of Firearm Brain Injury Survivors in the Traumatic Brain Injury Model Systems (TBIMS) National Database: A Comparison of Assault and Self-Inflicted Injury Survivors.

PubMed

Bertisch, Hilary; Krellman, Jason W; Bergquist, Thomas F; Dreer, Laura E; Ellois, Valerie; Bushnik, Tamara

2017-11-01

To characterize and compare subgroups of survivors with assault-related versus self-inflicted traumatic brain injuries (TBIs) via firearms at the time of inpatient rehabilitation and at 1-, 2-, and 5-year follow-up. Secondary analysis of data from the Traumatic Brain Injury Model Systems National Database (TBIMS NDB), a multicenter, longitudinal cohort study. Retrospective analyses of a subset of individuals enrolled in the TBIMS NDB. Individuals 16 years and older (N=399; 310 via assault, 89 via self-inflicted injury) with a primary diagnosis of TBI caused by firearm injury enrolled in the TBIMS NDB. Not applicable. Disability Rating Scale, Glasgow Outcome Scale-Extended, sociodemographic variables (sex, age, race, marital status), injury-related/acute care information (posttraumatic amnesia, loss of consciousness, time from injury to acute hospital discharge), and mental health variables (substance use history, psychiatric hospitalizations, suicide history, incarcerations). Individuals who survived TBI secondary to a firearm injury differed by injury mechanism (assault vs self-inflicted) on critical demographic, injury-related/acute care, and mental health variables at inpatient rehabilitation and across long-term recovery. Groups differed in terms of geographic area, age, ethnicity, education, marital status, admission Glasgow Coma Scale score, and alcohol abuse, suicide attempts, and psychiatric hospitalizations at various time points. These findings have implications for prevention (eg, mental health programming and access to firearms in targeted areas) and for rehabilitation planning (eg, by incorporating training with coping strategies and implementation of addictions-related services) for firearm-related TBI, based on subtype of injury. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

The family experiences of in-hospital care questionnaire in severe traumatic brain injury (FECQ-TBI): a validation study.

PubMed

Anke, Audny; Manskow, Unn Sollid; Friborg, Oddgeir; Røe, Cecilie; Arntzen, Cathrine

2016-11-28

Family members are important for support and care of their close relative after severe traumas, and their experiences are vital health care quality indicators. The objective was to describe the development of the Family Experiences of in-hospital Care Questionnaire for family members of patients with severe Traumatic Brain Injury (FECQ-TBI), and to evaluate its psychometric properties and validity. The design of the study is a Norwegian multicentre study inviting 171 family members. The questionnaire developmental process included a literature review, use of an existing instrument (the parent experience of paediatric care questionnaire), focus group with close family members, as well as expert group judgments. Items asking for family care experiences related to acute wards and rehabilitation were included. Several items of the paediatric care questionnaire were removed or the wording of the items was changed to comply with the present purpose. Questions covering experiences with the inpatient rehabilitation period, the discharge phase, the family experiences with hospital facilities, the transfer between departments and the economic needs of the family were added. The developed questionnaire was mailed to the participants. Exploratory factor analyses were used to examine scale structure, in addition to screening for data quality, and analyses of internal consistency and validity. The questionnaire was returned by 122 (71%) of family members. Principal component analysis extracted six dimensions (eigenvalues > 1.0): acute organization and information (10 items), rehabilitation organization (13 items), rehabilitation information (6 items), discharge (4 items), hospital facilities-patients (4 items) and hospital facilities-family (2 items). Items related to the acute phase were comparable to items in the two dimensions of rehabilitation: organization and information. All six subscales had high Cronbach's alpha coefficients >0.80. The construct validity was

A Wireless Intracranial Brain Deformation Sensing System for Blast-Induced Traumatic Brain Injury

PubMed Central

Song, S.; Race, N. S.; Kim, A.; Zhang, T.; Shi, R.; Ziaie, B.

2015-01-01

Blast-induced traumatic brain injury (bTBI) has been linked to a multitude of delayed-onset neurodegenerative and neuropsychiatric disorders, but complete understanding of their pathogenesis remains elusive. To develop mechanistic relationships between bTBI and post-blast neurological sequelae, it is imperative to characterize the initiating traumatic mechanical events leading to eventual alterations of cell, tissue, and organ structure and function. This paper presents a wireless sensing system capable of monitoring the intracranial brain deformation in real-time during the event of a bTBI. The system consists of an implantable soft magnet and an external head-mounted magnetic sensor that is able to measure the field in three dimensions. The change in the relative position of the soft magnet WITH respect to the external sensor as the result of the blast wave induces changes in the magnetic field. The magnetic field data in turn is used to extract the temporal and spatial motion of the brain under the blast wave in real-time. The system has temporal and spatial resolutions of 5 μs and 10 μm. Following the characterization and validation of the sensor system, we measured brain deformations in a live rodent during a bTBI. PMID:26586273

Diffusion Tensor Imaging Reveals White Matter Injury in a Rat Model of Repetitive Blast-Induced Traumatic Brain Injury

PubMed Central

Calabrese, Evan; Du, Fu; Garman, Robert H.; Johnson, G. Allan; Riccio, Cory; Tong, Lawrence C.

2014-01-01

Abstract Blast-induced traumatic brain injury (bTBI) is one of the most common combat-related injuries seen in U.S. military personnel, yet relatively little is known about the underlying mechanisms of injury. In particular, the effects of the primary blast pressure wave are poorly understood. Animal models have proven invaluable for the study of primary bTBI, because it rarely occurs in isolation in human subjects. Even less is known about the effects of repeated primary blast wave exposure, but existing data suggest cumulative increases in brain damage with a second blast. MRI and, in particular, diffusion tensor imaging (DTI), have become important tools for assessing bTBI in both clinical and preclinical settings. Computational statistical methods such as voxelwise analysis have shown promise in localizing and quantifying bTBI throughout the brain. In this study, we use voxelwise analysis of DTI to quantify white matter injury in a rat model of repetitive primary blast exposure. Our results show a significant increase in microstructural damage with a second blast exposure, suggesting that primary bTBI may sensitize the brain to subsequent injury. PMID:24392843

Considerations for animal models of blast-related traumatic brain injury and chronic traumatic encephalopathy.

PubMed

Goldstein, Lee E; McKee, Ann C; Stanton, Patric K

2014-01-01

The association of military blast exposure and brain injury was first appreciated in World War I as commotio cerebri, and later as shell shock. Similar injuries sustained in modern military conflicts are now classified as mild traumatic brain injury (TBI). Recent research has yielded new insights into the mechanisms by which blast exposure leads to acute brain injury and chronic sequelae, including postconcussive syndrome, post-traumatic stress disorder, post-traumatic headache, and chronic traumatic encephalopathy, a tau protein neurodegenerative disease. Impediments to delivery of effective medical care for individuals affected by blast-related TBI include: poor insight into the heterogeneity of neurological insults induced by blast exposure; limited understanding of the mechanisms by which blast exposure injures the brain and triggers sequelae; failure to appreciate interactive injuries that affect frontal lobe function, pituitary regulation, and neurovegetative homeostasis; unknown influence of genetic risk factors, prior trauma, and comorbidities; absence of validated diagnostic criteria and clinical nosology that differentiate clinical endophenotypes; and lack of empirical evidence to guide medical management and therapeutic intervention. While clinicopathological analysis can provide evidence of correlative association, experimental use of animal models remains the primary tool for establishing causal mechanisms of disease. However, the TBI field is confronted by a welter of animal models with varying clinical relevance, thereby impeding scientific coherence and hindering translational progress. Animal models of blast TBI will be far more translationally useful if experimental emphasis focuses on accurate reproduction of clinically relevant endpoints (output) rather than scaled replication of idealized blast shockwaves (input). The utility of an animal model is dependent on the degree to which the model recapitulates pathophysiological mechanisms

Considerations for animal models of blast-related traumatic brain injury and chronic traumatic encephalopathy

PubMed Central

2014-01-01

The association of military blast exposure and brain injury was first appreciated in World War I as commotio cerebri, and later as shell shock. Similar injuries sustained in modern military conflicts are now classified as mild traumatic brain injury (TBI). Recent research has yielded new insights into the mechanisms by which blast exposure leads to acute brain injury and chronic sequelae, including postconcussive syndrome, post-traumatic stress disorder, post-traumatic headache, and chronic traumatic encephalopathy, a tau protein neurodegenerative disease. Impediments to delivery of effective medical care for individuals affected by blast-related TBI include: poor insight into the heterogeneity of neurological insults induced by blast exposure; limited understanding of the mechanisms by which blast exposure injures the brain and triggers sequelae; failure to appreciate interactive injuries that affect frontal lobe function, pituitary regulation, and neurovegetative homeostasis; unknown influence of genetic risk factors, prior trauma, and comorbidities; absence of validated diagnostic criteria and clinical nosology that differentiate clinical endophenotypes; and lack of empirical evidence to guide medical management and therapeutic intervention. While clinicopathological analysis can provide evidence of correlative association, experimental use of animal models remains the primary tool for establishing causal mechanisms of disease. However, the TBI field is confronted by a welter of animal models with varying clinical relevance, thereby impeding scientific coherence and hindering translational progress. Animal models of blast TBI will be far more translationally useful if experimental emphasis focuses on accurate reproduction of clinically relevant endpoints (output) rather than scaled replication of idealized blast shockwaves (input). The utility of an animal model is dependent on the degree to which the model recapitulates pathophysiological mechanisms

Biomarkers of traumatic injury are transported from brain to blood via the glymphatic system.

PubMed

Plog, Benjamin A; Dashnaw, Matthew L; Hitomi, Emi; Peng, Weiguo; Liao, Yonghong; Lou, Nanhong; Deane, Rashid; Nedergaard, Maiken

2015-01-14

The nonspecific and variable presentation of traumatic brain injury (TBI) has motivated an intense search for blood-based biomarkers that can objectively predict the severity of injury. However, it is not known how cytosolic proteins released from traumatized brain tissue reach the peripheral blood. Here we show in a murine TBI model that CSF movement through the recently characterized glymphatic pathway transports biomarkers to blood via the cervical lymphatics. Clinically relevant manipulation of glymphatic activity, including sleep deprivation and cisternotomy, suppressed or eliminated TBI-induced increases in serum S100β, GFAP, and neuron specific enolase. We conclude that routine TBI patient management may limit the clinical utility of blood-based biomarkers because their brain-to-blood transport depends on glymphatic activity. Copyright © 2015 the authors 0270-6474/15/350518-09$15.00/0.

A phase I study of WR-2721 in combination with total body irradiation (TBI) in patients with refractory lymphoid malignancies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coia, L.; Krigel, R.; Hanks, G.

This Phase I study was designed to establish the maximum tolerated dose (MTD) of WR-2721 when given twice weekly with total body irradiation (TBI) in the treatment of patients with advanced refractory lymphoid malignancies and to define the toxicities of this combination and schedule. Patients eligible for this study had advanced recurrent indolent non-Hodgkin's lymphoma (NHL) or chronic lymphocytic leukemia (CLL). Patients had symptomatic or progressive disease, a performance status of 0, 1, or 2, and adequate bone marrow, hepatic, and renal function. Only patients failing one or two regimens of prior chemotherapy were eligible. Patients who had received priormore » extended field irradiation were ineligible. Patients received TBI twice weekly (Tuesday and Friday) to a total of 10 doses at 15 cGy/fx. WR-2721 was given intravenously over 15 min beginning 30 min before irradiation. The escalation of WR-2721 was Level 1: 740 mg/m2 and Level 2: 910 mg/m2. The MTD of WR-2721 was that dose which produced predictable and reversible toxicity and would not interfere with patient well-being. Seven patients were entered onto the study, three at 740 mg/m2 and four at 910 mg/m2. Five patients had CLL and two patients small lymphocytic NHL. No patient had hypotension or nausea requiring reduction in dose level or even interruption of infusion of WR-2721. At 740 mg/m2 no grade 3 or 4 toxicities related to WR-2721 were observed, but two patients could not complete treatment because of TBI-induced prolonged thrombocytopenia following treatments 5 and 8. One patient completed all 10 treatments. At 910 mg/m2 of WR-2721, two patients requested removal from study because of malaise, one after 5 cycles and one after 7 cycles. One patient completed all 10 treatments.« less

Clinical application of the OneDose™ Patient Dosimetry System for total body irradiation

NASA Astrophysics Data System (ADS)

Best, S.; Ralston, A.; Suchowerska, N.

2005-12-01

The OneDose™ Patient Dosimetry System (Sicel Technologies) is a new dosimeter based on metal oxide semiconductor field-effect transistor technology and designed for the in vivo measurement of patient dose during radiotherapy. In vivo dosimetry for total body irradiation (TBI) is challenging due to the extended treatment distance, low dose rates and beam spoilers. Phantom results confirm the suitability of the dosimeter for TBI in terms of inherent build-up, post-irradiation fading, accuracy, reproducibility, linearity and temperature dependence. Directional dependence is significant and should be taken into account. The OneDose™ dosimeters were also trialed in vivo for two TBI patients and the dose measured compared to conventional dosimeter measurements using an ionization chamber and thermoluminescent dosimeters (TLD), with agreement to within 2.2% and 3.9%, respectively. Phantom and patient results confirm that the OneDose™ patient dosimetry system is a practical and convenient alternative to TLDs for TBI in vivo dosimetry. For increased confidence in results with this dosimeter, we recommend that two dosimeters be used for each site of interest.

Clinical application of the OneDose Patient Dosimetry System for total body irradiation.

PubMed

Best, S; Ralston, A; Suchowerska, N

2005-12-21

The OneDose Patient Dosimetry System (Sicel Technologies) is a new dosimeter based on metal oxide semiconductor field-effect transistor technology and designed for the in vivo measurement of patient dose during radiotherapy. In vivo dosimetry for total body irradiation (TBI) is challenging due to the extended treatment distance, low dose rates and beam spoilers. Phantom results confirm the suitability of the dosimeter for TBI in terms of inherent build-up, post-irradiation fading, accuracy, reproducibility, linearity and temperature dependence. Directional dependence is significant and should be taken into account. The OneDose dosimeters were also trialed in vivo for two TBI patients and the dose measured compared to conventional dosimeter measurements using an ionization chamber and thermoluminescent dosimeters (TLD), with agreement to within 2.2% and 3.9%, respectively. Phantom and patient results confirm that the OneDose patient dosimetry system is a practical and convenient alternative to TLDs for TBI in vivo dosimetry. For increased confidence in results with this dosimeter, we recommend that two dosimeters be used for each site of interest.

Ethyl pyruvate protects against blood-brain barrier damage and improves long-term neurological outcomes in a rat model of traumatic brain injury.

PubMed

Shi, Hong; Wang, Hai-Lian; Pu, Hong-Jian; Shi, Ye-Jie; Zhang, Jia; Zhang, Wen-Ting; Wang, Guo-Hua; Hu, Xiao-Ming; Leak, Rehana K; Chen, Jun; Gao, Yan-Qin

2015-04-01

Many traumatic brain injury (TBI) survivors sustain neurological disability and cognitive impairments due to the lack of defined therapies to reduce TBI-induced long-term brain damage. Ethyl pyruvate (EP) has shown neuroprotection in several models of acute brain injury. The present study therefore investigated the potential beneficial effect of EP on long-term outcomes after TBI and the underlying mechanisms. Male adult rats were subjected to unilateral controlled cortical impact injury. EP was injected intraperitoneally 15 min after TBI and again at 12, 24, 36, 48, and 60 h after TBI. Neurological deficits, blood-brain barrier (BBB) integrity, and neuroinflammation were assessed. Ethyl pyruvate improved sensorimotor and cognitive functions and ameliorated brain tissue damage up to 28 day post-TBI. BBB breach and brain edema were attenuated by EP at 48 h after TBI. EP suppressed matrix metalloproteinase (MMP)-9 production from peripheral neutrophils and reduced the number of MMP-9-overproducing neutrophils in the spleen, and therefore mitigated MMP-9-mediated BBB breakdown. Moreover, EP exerted potent antiinflammatory effects in cultured microglia and inhibited the elevation of inflammatory mediators in the brain after TBI. Ethyl pyruvate confers long-term neuroprotection against TBI, possibly through breaking the vicious cycle among MMP-9-mediated BBB disruption, neuroinflammation, and long-lasting brain damage. © 2014 John Wiley & Sons Ltd.

Modeling the Prospective Relationships of Impairment, Injury Severity, and Participation to Quality of Life Following Traumatic Brain Injury

PubMed Central

Kalpinski, Ryan J.; Williamson, Meredith L. C.; Elliott, Timothy R.; Berry, Jack W.; Underhill, Andrea T.; Fine, Philip R.

2013-01-01

Identifying reliable predictors of positive adjustment following traumatic brain injury (TBI) remains an important area of inquiry. Unfortunately, much of available research examines direct relationships between predictor variables and outcomes without attending to the contextual relationships that can exist between predictor variables. Relying on theoretical models of well-being, we examined a theoretical model of adjustment in which the capacity to engage in intentional activities would be prospectively associated with greater participation, which in turn would predict subsequent life satisfaction and perceived health assessed at a later time. Structural equation modeling of data collected from 312 individuals (226 men, 86 women) with TBI revealed that two elements of participation—mobility and occupational activities—mediated the prospective influence of functional independence and injury severity to optimal adjustment 60 months following medical discharge for TBI. The model accounted for 21% of the variance in life satisfaction and 23% of the variance in self-rated health. Results indicate that the effects of functional independence and injury severity to optimal adjustment over time may be best understood in the context of participation in meaningful, productive activities. Implications for theoretical models of well-being and for clinical interventions that promote adjustmentafter TBI are discussed. PMID:24199186

Acute vitreoretinal trauma and inflammation after traumatic brain injury in mice.

PubMed

Evans, Lucy P; Newell, Elizabeth A; Mahajan, MaryAnn; Tsang, Stephen H; Ferguson, Polly J; Mahoney, Jolonda; Hue, Christopher D; Vogel, Edward W; Morrison, Barclay; Arancio, Ottavio; Nichols, Russell; Bassuk, Alexander G; Mahajan, Vinit B

2018-03-01

Limited attention has been given to ocular injuries associated with traumatic brain injury (TBI). The retina is an extension of the central nervous system and evaluation of ocular damage may offer a less-invasive approach to gauge TBI severity and response to treatment. We aim to characterize acute changes in the mouse eye after exposure to two different models of TBI to assess the utility of eye damage as a surrogate to brain injury. A model of blast TBI (bTBI) using a shock tube was compared to a lateral fluid percussion injury model (LFPI) using fluid pressure applied directly to the brain. Whole eyes were collected from mice 3 days post LFPI and 24 days post bTBI and were evaluated histologically using a hematoxylin and eosin stain. bTBI mice showed evidence of vitreous detachment in the posterior chamber in addition to vitreous hemorrhage with inflammatory cells. Subretinal hemorrhage, photoreceptor degeneration, and decreased cellularity in the retinal ganglion cell layer was also seen in bTBI mice. In contrast, eyes of LFPI mice showed evidence of anterior uveitis and subcapsular cataracts. We demonstrated that variations in the type of TBI can result in drastically different phenotypic changes within the eye. As such, molecular and phenotypic changes in the eye following TBI may provide valuable information regarding the mechanism, severity, and ongoing pathophysiology of brain injury. Because vitreous samples are easily obtained, molecular changes within the eye could be utilized as biomarkers of TBI in human patients.

Transplantation of human neural stem cells restores cognition in an immunodeficient rodent model of traumatic brain injury.

PubMed

Haus, Daniel L; López-Velázquez, Luci; Gold, Eric M; Cunningham, Kelly M; Perez, Harvey; Anderson, Aileen J; Cummings, Brian J

2016-07-01

Traumatic brain injury (TBI) in humans can result in permanent tissue damage and has been linked to cognitive impairment that lasts years beyond the initial insult. Clinically effective treatment strategies have yet to be developed. Transplantation of human neural stem cells (hNSCs) has the potential to restore cognition lost due to injury, however, the vast majority of rodent TBI/hNSC studies to date have evaluated cognition only at early time points, typically <1month post-injury and cell transplantation. Additionally, human cell engraftment and long-term survival in rodent models of TBI has been difficult to achieve due to host immunorejection of the transplanted human cells, which confounds conclusions pertaining to transplant-mediated behavioral improvement. To overcome these shortfalls, we have developed a novel TBI xenotransplantation model that utilizes immunodeficient athymic nude (ATN) rats as the host recipient for the post-TBI transplantation of human embryonic stem cell (hESC) derived NSCs and have evaluated cognition in these animals at long-term (≥2months) time points post-injury. We report that immunodeficient ATN rats demonstrate hippocampal-dependent spatial memory deficits (Novel Place, Morris Water Maze), but not non-spatial (Novel Object) or emotional/anxiety-related (Elevated Plus Maze, Conditioned Taste Aversion) deficits, at 2-3months post-TBI, confirming that ATN rats recapitulate some of the cognitive deficits found in immunosufficient animal strains. Approximately 9-25% of transplanted hNSCs survived for at least 5months post-transplantation and differentiated into mature neurons (NeuN, 18-38%), astrocytes (GFAP, 13-16%), and oligodendrocytes (Olig2, 11-13%). Furthermore, while this model of TBI (cortical impact) targets primarily cortex and the underlying hippocampus and generates a large lesion cavity, hNSC transplantation facilitated cognitive recovery without affecting either lesion volume or total spared cortical or hippocampal

Assessment of processing speed in children with mild TBI: a "first look" at the validity of pediatric ImPACT.

PubMed

Newman, Julie B; Reesman, Jennifer H; Vaughan, Christopher G; Gioia, Gerard A

2013-01-01

Deficit in the speed of cognitive processing is a commonly identified neuropsychological change in children recovering from a mild TBI. However, there are few validated child assessment instruments that allow for serial assessment over the course of recovery in this population. Pediatric ImPACT is a novel measure that purports to assess cognitive speed, learning, and efficiency in this population. The current study sought to validate the use of this new measure by comparing it to traditional paper and pencil measures of processing speed. One hundred and sixty-four children (71% male) age 5-12 with mild TBI evaluated in an outpatient concussion clinic were administered Pediatric ImPACT and other neuropsychological test measures as part of a flexible test battery. Performance on the Response Speed Composite of Pediatric ImPACT was more strongly associated with other measures of cognitive processing speed, than with measures of immediate/working memory and learning/memory in this sample of injured children. There is preliminary support for convergent and discriminant validity of Pediatric ImPACT as a measure for use in post-concussion evaluations of processing speed in children.

Non-invasively estimated ICP pulse amplitude strongly correlates with outcome after TBI.

PubMed

Budohoski, Karol P; Schmidt, Bernhard; Smielewski, Peter; Kasprowicz, Magdalena; Plontke, Ronny; Pickard, John D; Klingelhöfer, Jurgen; Czosnyka, Marek

2012-01-01

An existing monitoring database of brain signal recordings in patients with head injury has been re-evaluated with regard to the accuracy of estimation of non-invasive ICP (nICP) and its components, with a particular interest in the implications for outcome after head injury. Middle cerebral artery blood flow velocity (FV), ICP and arterial blood pressure (ABP) were recorded. Non-invasive ICP (nICP) was calculated using a mathematical model. Other signals analysed included components of ICP (n" indicates non-invasive): ICP pulse amplitude (Amp, nAmp), amplitude of the respiratory component (Resp, nResp), amplitude of slow vasogenic waves of ICP (Slow, nSlow) and index of compensatory reserve (RAP, nRAP). Mean values of analysed signals were compared against each other and between patients who died and survived. The correlation between ICP and nICP was moderately strong, R = 0.51 (95% prediction interval [PI] 17 mm Hg). The components of nICP and ICP were also moderately correlated with each other: the strongest correlation was observed for Resp vs. nResp (r = 0.66), while weaker for Amp vs. nAmp (r = 0.41). Non-invasive pulse amplitude of ICP showed the strongest association with outcome, with the -difference between those who survived and those who died reaching a significance level of p < 0.000001. When compared between patients who died and who survived mean nAmp showed the greatest difference, suggesting its potential to predict mortality after TBI.

Radiation protocols determine acute graft-versus-host disease incidence after allogeneic bone marrow transplantation in murine models.

PubMed

Schwarte, Sebastian; Bremer, Michael; Fruehauf, Joerg; Sorge, Yanina; Skubich, Susanne; Hoffmann, Matthias W

2007-09-01

Effects of radiation sources used for total body irradiation (TBI) on Graft-versus-Host Disease (GvHD) induction were examined. In a T cell receptor (TCR) transgenic mouse model, single fraction TBI was performed with different radiation devices ((60)Cobalt; (137)Cesium; 6 MV linear accelerator), dose rates (0.85; 1.5; 2.9; 5 Gy/min) and total doses before allogeneic bone marrow transplantation (BMT). Recipients were observed for 120 days. Different tissues were examined histologically. Acute GvHD was induced by a dose rate of 0.85 Gy/min ((60)Cobalt) and a total dose of 9 Gy and injection of 5 x 10(5) lymph node cells plus 5 x 10(6) bone marrow cells. Similar results were obtained using 6 MV linear accelerator- (linac-) photons with a dose rate of 1.5 Gy/min and 0.85 Gy/min, a total dose of 9.5 Gy and injection of same cell numbers. TBI with (137)Cesium (dose rate: 2.5 Gy/min) did not lead reproducibly to lethal acute GvHD. Experimental TBI in murine models may induce different immunological responses, depending on total energy, total single dose and dose rate. GvHD might also be induced by TBI with low dose rates.

Traumatic brain injury produced by exposure to blasts, a critical problem in current wars: biomarkers, clinical studies, and animal models

NASA Astrophysics Data System (ADS)

Dixon, C. Edward

2011-06-01

Traumatic brain injury (TBI) resulting from exposure to blast energy released by Improvised Explosive Devices (IEDs) has been recognized as the "signature injury" of Operation Iraqi Freedom and Operation Enduring Freedom. Repeated exposure to mild blasts may produce subtle deficits that are difficult to detect and quantify. Several techniques have been used to detect subtle brain dysfunction including neuropsychological assessments, computerized function testing and neuroimaging. Another approach is based on measurement of biologic substances (e.g. proteins) that are released into the body after a TBI. Recent studies measuring biomarkers in CSF and serum from patients with severe TBI have demonstrated the diagnostic, prognostic, and monitoring potential. Advancement of the field will require 1) biochemical mining for new biomarker candidates, 2) clinical validation of utility, 3) technical advances for more sensitive, portable detectors, 4) novel statistical approach to evaluate multiple biomarkers, and 5) commercialization. Animal models have been developed to simulate elements of blast-relevant TBI including gas-driven shock tubes to generate pressure waves similar to those produced by explosives. These models can reproduce hallmark clinical neuropathological responses such as neuronal degeneration and inflammation, as well as behavioral impairments. An important application of these models is to screen novel therapies and conduct proteomic, genomic, and lipodomic studies to mine for new biomarker candidates specific to blast relevant TBI.

A Model of Fatigue Following Traumatic Brain Injury.

PubMed

Ponsford, Jennie; Schönberger, Michael; Rajaratnam, Shantha M W

2015-01-01

Fatigue is one of the most frequent sequelae of traumatic brain injury (TBI), although its causes are poorly understood. This study investigated the interrelationships between fatigue and sleepiness, vigilance performance, depression, and anxiety, using a structural equation modeling approach. Seventy-two participants with moderate to severe TBI (78% males) were recruited a median of 305 days postinjury. They completed the Fatigue Severity Scale, a vigilance task, the Epworth Sleepiness Scale, and Hospital Anxiety and Depression Scale. A model of the interrelationships between the study variables was developed, tested, and modified with path analysis. The modified model had a good overall fit (χ2 = 1.3, P = .54; comparative fit index = 1.0; root-mean square error of approximation = 0.0; standardized root-mean square residual = 0.02). Most paths in this model were significant (P < .05). Fatigue predicted anxiety, depression, and daytime sleepiness. Depression predicted daytime sleepiness and poor vigilance, whereas anxiety tended to predict reduced daytime sleepiness. This model confirms the complexity of fatigue experience. It supports the hypothesis that fatigue after TBI is a cause, not a consequence, of anxiety, depression, and daytime sleepiness, which, in turn (especially depression), may exacerbate fatigue by affecting cognitive functioning. These findings suggest that to alleviate fatigue, it is important to address each of these factors. However, the findings need to be confirmed with a longitudinal research design.

Effect of Traumatic Brain Injury, Erythropoietin, and Anakinra on Hepatic Metabolizing Enzymes and Transporters in an Experimental Rat Model.

PubMed

Anderson, Gail D; Peterson, Todd C; Vonder Haar, Cole; Farin, Fred M; Bammler, Theo K; MacDonald, James W; Kantor, Eric D; Hoane, Michael R

2015-09-01

In contrast to considerable data demonstrating a decrease in cytochrome P450 (CYP) activity in inflammation and infection, clinically, traumatic brain injury (TBI) results in an increase in CYP and UDP glucuronosyltransferase (UGT) activity. The objective of this study was to determine the effects of TBI alone and with treatment with erythropoietin (EPO) or anakinra on the gene expression of hepatic inflammatory proteins, drug-metabolizing enzymes, and transporters in a cortical contusion impact (CCI) injury model. Microarray-based transcriptional profiling was used to determine the effect on gene expression at 24 h, 72 h, and 7 days post-CCI. Plasma cytokine and liver protein concentrations of CYP2D4, CYP3A1, EPHX1, and UGT2B7 were determined. There was no effect of TBI, TBI + EPO, or TBI + anakinra on gene expression of the inflammatory factors shown to be associated with decreased expression of hepatic metabolic enzymes in models of infection and inflammation. IL-6 plasma concentrations were increased in TBI animals and decreased with EPO and anakinra treatment. There was no significant effect of TBI and/or anakinra on gene expression of enzymes or transporters known to be involved in drug disposition. TBI + EPO treatment decreased the gene expression of Cyp2d4 at 72 h with a corresponding decrease in CYP2D4 protein at 72 h and 7 days. CYP3A1 protein was decreased at 24 h. In conclusion, EPO treatment may result in a significant decrease in the metabolism of Cyp-metabolized drugs. In contrast to clinical TBI, there was not a significant effect of experimental TBI on CYP or UGT metabolic enzymes.

High-sensitivity terahertz imaging of traumatic brain injury in a rat model

NASA Astrophysics Data System (ADS)

Zhao, Hengli; Wang, Yuye; Chen, Linyu; Shi, Jia; Ma, Kang; Tang, Longhuang; Xu, Degang; Yao, Jianquan; Feng, Hua; Chen, Tunan

2018-03-01

We demonstrated that different degrees of experimental traumatic brain injury (TBI) can be differentiated clearly in fresh slices of rat brain tissues using transmission-type terahertz (THz) imaging system. The high absorption region in THz images corresponded well with the injured area in visible images and magnetic resonance imaging results. The THz image and absorption characteristics of dehydrated paraffin-embedded brain slices and the hematoxylin and eosin (H&E)-stained microscopic images were investigated to account for the intrinsic differences in the THz images for the brain tissues suffered from different degrees of TBI and normal tissue aside from water. The THz absorption coefficients of rat brain tissues showed an increase in the aggravation of brain damage, particularly in the high-frequency range, whereas the cell density decreased as the order of mild, moderate, and severe TBI tissues compared with the normal tissue. Our results indicated that the different degrees of TBI were distinguishable owing to the different water contents and probable hematoma components distribution rather than intrinsic cell intensity. These promising results suggest that THz imaging has great potential as an alternative method for the fast diagnosis of TBI.

Assessing Neuro-Systemic & Behavioral Components in the Pathophysiology of Blast-Related Brain Injury

PubMed Central

Kobeissy, Firas; Mondello, Stefania; Tümer, Nihal; Toklu, Hale Z.; Whidden, Melissa A.; Kirichenko, Nataliya; Zhang, Zhiqun; Prima, Victor; Yassin, Walid; Anagli, John; Chandra, Namas; Svetlov, Stan; Wang, Kevin K. W.

2013-01-01

Among the U.S. military personnel, blast injury is among the leading causes of brain injury. During the past decade, it has become apparent that even blast injury as a form of mild traumatic brain injury (mTBI) may lead to multiple different adverse outcomes, such as neuropsychiatric symptoms and long-term cognitive disability. Blast injury is characterized by blast overpressure, blast duration, and blast impulse. While the blast injuries of a victim close to the explosion will be severe, majority of victims are usually at a distance leading to milder form described as mild blast TBI (mbTBI). A major feature of mbTBI is its complex manifestation occurring in concert at different organ levels involving systemic, cerebral, neuronal, and neuropsychiatric responses; some of which are shared with other forms of brain trauma such as acute brain injury and other neuropsychiatric disorders such as post-traumatic stress disorder. The pathophysiology of blast injury exposure involves complex cascades of chronic psychological stress, autonomic dysfunction, and neuro/systemic inflammation. These factors render blast injury as an arduous challenge in terms of diagnosis and treatment as well as identification of sensitive and specific biomarkers distinguishing mTBI from other non-TBI pathologies and from neuropsychiatric disorders with similar symptoms. This is due to the “distinct” but shared and partially identified biochemical pathways and neuro-histopathological changes that might be linked to behavioral deficits observed. Taken together, this article aims to provide an overview of the current status of the cellular and pathological mechanisms involved in blast overpressure injury and argues for the urgent need to identify potential biomarkers that can hint at the different mechanisms involved. PMID:24312074

Assessing neuro-systemic & behavioral components in the pathophysiology of blast-related brain injury.

PubMed

Kobeissy, Firas; Mondello, Stefania; Tümer, Nihal; Toklu, Hale Z; Whidden, Melissa A; Kirichenko, Nataliya; Zhang, Zhiqun; Prima, Victor; Yassin, Walid; Anagli, John; Chandra, Namas; Svetlov, Stan; Wang, Kevin K W

2013-11-21

Among the U.S. military personnel, blast injury is among the leading causes of brain injury. During the past decade, it has become apparent that even blast injury as a form of mild traumatic brain injury (mTBI) may lead to multiple different adverse outcomes, such as neuropsychiatric symptoms and long-term cognitive disability. Blast injury is characterized by blast overpressure, blast duration, and blast impulse. While the blast injuries of a victim close to the explosion will be severe, majority of victims are usually at a distance leading to milder form described as mild blast TBI (mbTBI). A major feature of mbTBI is its complex manifestation occurring in concert at different organ levels involving systemic, cerebral, neuronal, and neuropsychiatric responses; some of which are shared with other forms of brain trauma such as acute brain injury and other neuropsychiatric disorders such as post-traumatic stress disorder. The pathophysiology of blast injury exposure involves complex cascades of chronic psychological stress, autonomic dysfunction, and neuro/systemic inflammation. These factors render blast injury as an arduous challenge in terms of diagnosis and treatment as well as identification of sensitive and specific biomarkers distinguishing mTBI from other non-TBI pathologies and from neuropsychiatric disorders with similar symptoms. This is due to the "distinct" but shared and partially identified biochemical pathways and neuro-histopathological changes that might be linked to behavioral deficits observed. Taken together, this article aims to provide an overview of the current status of the cellular and pathological mechanisms involved in blast overpressure injury and argues for the urgent need to identify potential biomarkers that can hint at the different mechanisms involved.

Group therapy use and its impact on the outcomes of inpatient rehabilitation following traumatic brain injury: Data from TBI-PBE project

PubMed Central

Hammond, Flora M.; Barrett, Ryan; Dijkers, Marcel P.; Zanca, Jeanne M.; Horn, Susan D.; Smout, Randall J.; Guerrier, Tami; Hauser, Elizabeth; Dunning, Megan R.

2015-01-01

Objective To describe the amount and content of group therapies provided during inpatient rehabilitation for traumatic brain injury (TBI), and assess the relationships of group therapy with patient, injury, and treatment factors as well as outcomes. Design Prospective observational cohort. Setting Inpatient rehabilitation. Participants 2,130 consecutive admissions for initial TBI rehabilitation at 10 inpatient rehabilitation facilities (9 in US and 1 Canada) from October 2008 to September 2011. Interventions n/a Main Outcome Measure(s) proportion of sessions that were group therapy (two or more patients were treated simultaneously by one or more clinicians); proportion of patients receiving group therapy; type of activity performed and amount of time spent in group therapy, by discipline; rehabilitation length of stay (RLOS); discharge location; FIM Cognitive and Motor scores at discharge. Results 79% of patients received at least 1 session of group therapy, with group therapy accounting for 13.7% of all therapy sessions and 15.8% of therapy hours. On average, patients spent 2.9 hours per week in group therapy. The greatest proportion of treatment time in group format was in Therapeutic Recreation (25.6%), followed by Speech Therapy (16.2%), Occupational Therapy (10.4%), Psychology (8.1%), and Physical Therapy (7.9%). Group therapy time and type of treatment activities varied among admission FIM cognitive subgroups and treatment sites. Several factors appear to be predictive of receiving group therapy, with treatment site being a major influence. However, group therapy as a whole offered little explanation of differences in the outcomes studied. Conclusion(s) Group therapy is commonly used in TBI rehabilitation, to varying degrees among disciplines, sites, and cognitive impairment subgroups. Various therapeutic activities take place in group therapy, indicating its perceived value in addressing many domains of functioning. Variation in outcomes is not explained

'The biggest thing is trying to live for two people': Spousal experiences of supporting decision-making participation for partners with TBI.

PubMed

Knox, Lucy; Douglas, Jacinta M; Bigby, Christine

2015-01-01

To understand how the spouses of individuals with severe TBI experience the process of supporting their partners with decision-making. This study adopted a constructivist grounded theory approach, with data consisting of in-depth interviews conducted with spouses over a 12-month period. Data were analysed through an iterative process of open and focused coding, identification of emergent categories and exploration of relationships between categories. Participants were four spouses of individuals with severe TBI (with moderate-severe disability). Spouses had shared committed relationships (marriage or domestic partnerships) for at least 4 years at initial interview. Three spouses were in relationships that had commenced following injury. Two main themes emerged from the data. The first identified the saliency of the relational space in which decision-making took place. The second revealed the complex nature of decision-making within the spousal relationship. Spouses experience decision-making as a complex multi-stage process underpinned by a number of relational factors. Increased understanding of this process can guide health professionals in their provision of support for couples in exploring decision-making participation after injury.

Acute Radiation Syndrome Severity Score System in Mouse Total-Body Irradiation Model.

PubMed

Ossetrova, Natalia I; Ney, Patrick H; Condliffe, Donald P; Krasnopolsky, Katya; Hieber, Kevin P

2016-08-01

Radiation accidents or terrorist attacks can result in serious consequences for the civilian population and for military personnel responding to such emergencies. The early medical management situation requires quantitative indications for early initiation of cytokine therapy in individuals exposed to life-threatening radiation doses and effective triage tools for first responders in mass-casualty radiological incidents. Previously established animal (Mus musculus, Macaca mulatta) total-body irradiation (γ-exposure) models have evaluated a panel of radiation-responsive proteins that, together with peripheral blood cell counts, create a multiparametic dose-predictive algorithm with a threshold for detection of ~1 Gy from 1 to 7 d after exposure as well as demonstrate the acute radiation syndrome severity score systems created similar to the Medical Treatment Protocols for Radiation Accident Victims developed by Fliedner and colleagues. The authors present a further demonstration of the acute radiation sickness severity score system in a mouse (CD2F1, males) TBI model (1-14 Gy, Co γ-rays at 0.6 Gy min) based on multiple biodosimetric endpoints. This includes the acute radiation sickness severity Observational Grading System, survival rate, weight changes, temperature, peripheral blood cell counts and radiation-responsive protein expression profile: Flt-3 ligand, interleukin 6, granulocyte-colony stimulating factor, thrombopoietin, erythropoietin, and serum amyloid A. Results show that use of the multiple-parameter severity score system facilitates identification of animals requiring enhanced monitoring after irradiation and that proteomics are a complementary approach to conventional biodosimetry for early assessment of radiation exposure, enhancing accuracy and discrimination index for acute radiation sickness response categories and early prediction of outcome.

Cost prediction following traumatic brain injury: model development and validation.

PubMed

Spitz, Gershon; McKenzie, Dean; Attwood, David; Ponsford, Jennie L

2016-02-01

The ability to predict costs following a traumatic brain injury (TBI) would assist in planning treatment and support services by healthcare providers, insurers and other agencies. The objective of the current study was to develop predictive models of hospital, medical, paramedical, and long-term care (LTC) costs for the first 10 years following a TBI. The sample comprised 798 participants with TBI, the majority of whom were male and aged between 15 and 34 at time of injury. Costing information was obtained for hospital, medical, paramedical, and LTC costs up to 10 years postinjury. Demographic and injury-severity variables were collected at the time of admission to the rehabilitation hospital. Duration of PTA was the most important single predictor for each cost type. The final models predicted 44% of hospital costs, 26% of medical costs, 23% of paramedical costs, and 34% of LTC costs. Greater costs were incurred, depending on cost type, for individuals with longer PTA duration, obtaining a limb or chest injury, a lower GCS score, older age at injury, not being married or defacto prior to injury, living in metropolitan areas, and those reporting premorbid excessive or problem alcohol use. This study has provided a comprehensive analysis of factors predicting various types of costs following TBI, with the combination of injury-related and demographic variables predicting 23-44% of costs. PTA duration was the strongest predictor across all cost categories. These factors may be used for the planning and case management of individuals following TBI. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

In-Vitro Approaches for Studying Blast-Induced Traumatic Brain Injury

PubMed Central

Chen, Yung Chia; Smith, Douglas H.

2009-01-01

Abstract Traumatic brain injury caused by explosive or blast events is currently divided into four phases: primary, secondary, tertiary, and quaternary blast injury. These phases of blast-induced traumatic brain injury (bTBI) are biomechanically distinct, and can be modeled in both in-vivo and in-vitro systems. The purpose of this review is to consider the mechanical phases of bTBI, how these phases are reproduced with in-vitro models, and to review findings from these models to assess how each phase of bTBI can be examined in more detail. Highlighted are some important gaps in the literature that may be addressed in the future to better identify the exact contributing mechanisms for bTBI. These in-vitro models, viewed in combination with in-vivo models and clinical studies, can be used to assess both the mechanisms and possible treatments for this type of trauma. PMID:19397424

The Effects of Intimate Partner Violence and Probable Traumatic Brain Injury on Central Nervous System Symptoms.

PubMed

Campbell, Jacquelyn C; Anderson, Jocelyn C; McFadgion, Akosoa; Gill, Jessica; Zink, Elizabeth; Patch, Michelle; Callwood, Gloria; Campbell, Doris

2018-06-01

Abused women often report a wide range of physical and psychological symptoms that present challenges to providers. Specifically, injuries to the head or strangulation, may initiate neurological changes that contribute to central nervous system (CNS) symptoms. These symptoms are often attributed to mental health diagnoses in this population. The purpose of this analysis is to examine the prevalence of and associations between reported probable traumatic brain injury (TBI) and CNS symptoms in a sample of women of African descent. A convenience sample of 901 women of African descent from Baltimore, MD and the US Virgin Islands, aged 18-55, was used to examine relationships among self-reported intimate partner violence (IPV), TBI, and CNS symptoms. Data were collected via Audio Computer-Assisted Self-Interview. Abused women who experienced a probable TBI were more likely to report CNS symptoms than those who did not. When controlling for demographics, IPV, and mental health symptoms, probable TBI was associated with a two point increase in CNS symptom frequency score (95% confidence interval: 1.55-2.93, p < 0.001). Women who reported both probable TBI and IPV were more likely than their abused counterparts who reported no TBI to report CNS symptoms. This relationship held true even when controlling for symptoms of depression and post-traumatic stress disorder (PTSD). Clinicians working with women should be aware of TBI as a possible etiology for symptoms in abused women. Appropriate screening and treatment protocols should be designed and implemented across medical settings to improve outcomes for women who have experienced IPV and TBI.

Investigating a Proposed Model of Social Competence in Children With Traumatic Brain Injuries

PubMed Central

Rubin, Kenneth H.; Dennis, Maureen; Taylor, H. Gerry; Stancin, Terry; Gerhardt, Cynthia A.; Vannatta, Kathryn; Bigler, Erin D.; Yeates, Keith Owen

2016-01-01

Objective The goal of the current study was to test a proposed model of social competence for children who have suffered a traumatic brain injury (TBI). We hypothesized that both peer and teacher reports of social behavior would mediate the relation between intraindividual characteristics (e.g., executive function) and peer acceptance. Methods Participants were 52 children with TBI (M age = 10.29; M time after injury: 2.46 years). Severity of TBI ranged from complicated mild to severe. Classroom and laboratory measures were used to assess executive function, social behavior, and peer acceptance. Results Analyses revealed that peer reports of social behavior were a better mediator than teacher reports of the associations between executive function, social behaviors, and peer acceptance. Discussion The results underscore the importance of including peer reports of social behavior when developing interventions designed to improve the social, emotional, and behavioral outcomes of children with TBI. PMID:26374864

Regulation of Mitochondrial Function and Glutamatergic System Are the Target of Guanosine Effect in Traumatic Brain Injury.

PubMed

Dobrachinski, Fernando; da Rosa Gerbatin, Rogério; Sartori, Gláubia; Ferreira Marques, Naiani; Zemolin, Ana Paula; Almeida Silva, Luiz Fernando; Franco, Jeferson Luis; Freire Royes, Luiz Fernando; Rechia Fighera, Michele; Antunes Soares, Félix Alexandre

2017-04-01

Traumatic brain injury (TBI) is a highly complex multi-factorial disorder. Experimental trauma involves primary and secondary injury cascades that underlie delayed neuronal dysfunction and death. Mitochondrial dysfunction and glutamatergic excitotoxicity are the hallmark mechanisms of damage. Accordingly, a successful pharmacological intervention requires a multi-faceted approach. Guanosine (GUO) is known for its neuromodulator effects in various models of brain pathology, specifically those that involve the glutamatergic system. The aim of the study was to investigate the GUO effects against mitochondrial damage in hippocampus and cortex of rats subjected to TBI, as well as the relationship of this effect with the glutamatergic system. Adult male Wistar rats were subjected to a unilateral moderate fluid percussion brain injury (FPI) and treated 15 min later with GUO (7.5 mg/kg) or vehicle (saline 0.9%). Analyses were performed in hippocampus and cortex 3 h post-trauma and revealed significant mitochondrial dysfunction, characterized by a disrupted membrane potential, unbalanced redox system, decreased mitochondrial viability, and complex I inhibition. Further, disruption of Ca 2+ homeostasis and increased mitochondrial swelling was also noted. Our results showed that mitochondrial dysfunction contributed to decreased glutamate uptake and levels of glial glutamate transporters (glutamate transporter 1 and glutamate aspartate transporter), which leads to excitotoxicity. GUO treatment ameliorated mitochondrial damage and glutamatergic dyshomeostasis. Thus, GUO might provide a new efficacious strategy for the treatment acute physiological alterations secondary to TBI.

Brain oxygenation with a non-vasoactive perfluorocarbon emulsion in a rat model of traumatic brain injury.

PubMed

Abutarboush, Rania; Mullah, Saad H; Saha, Biswajit K; Haque, Ashraful; Walker, Peter B; Aligbe, Chioma; Pappas, Georgina; Tran Ho, Lam Thuy Vi; Arnaud, Francoise G; Auker, Charles R; McCarron, Richard M; Scultetus, Anke H; Moon-Massat, Paula

2018-04-01

The aim of this study was to assess, in two experiments, the safety and efficacy of the PFC emulsion Oxycyte as an oxygen therapeutic for TBI to test the hypothesis that early administration of this oxygen-carrying fluid post-TBI would improve brain tissue oxygenation (P bt O 2 ). The first experiment assessed the effects of Oxycyte on cerebral vasoactivity in healthy, uninjured rats using intravital microscopy. The second experiment investigated the effect of Oxycyte on cerebral P bt O 2 using the PQM in TBI model. Animals in the Oxycyte group received a single injection of Oxycyte (6 mL/kg) shortly after TBI, while NON animals received no treatment. Oxycyte did not cause vasoconstriction in small- (<50 μm) or medium- (50-100 μm) sized pial arterioles nor did it cause a significant change in blood pressure. Treatment with Oxycyte while breathing 100% O 2 did not improve P bt O 2 . However, in rats ventilated with ~40% O 2 , P bt O 2 improved to near pre-TBI values within 105 minutes after Oxycyte injection. Although Oxycyte did not cause cerebral vasoconstriction, its use at the dose tested while breathing 100% O 2 did not improve P bt O 2 following TBI. However, Oxycyte treatment while breathing a lower enriched oxygen concentration may improve P bt O 2 after TBI. © 2018 John Wiley & Sons Ltd.

The Relatives' Big Five Personality Influences the Trajectories of Recovery of Patients After Severe TBI: A Multilevel Analysis.

PubMed

Haller, Chiara S

2017-08-01

This study examines the influence of the personality of relatives on the trajectories of recovery of patients with severe traumatic brain injury (TBI). The present subsample (N = 376) of a larger population-based, prospective, 12-month multicenter cohort study in Switzerland (2007-2011) consists of patients with severe TBI (age ≥ 16) and their relatives. The predictors are the NEO Five-Factor Inventory and time (trajectory of functioning of the patient over time). The outcomes are the patients' (a) neurological functioning; (b) reported emotional, interpersonal, cognitive, and total functioning post-injury; and (c) health-related quality of life (HRQoL). The covariates included Abbreviated Injury Scale score of the head region and age. Results for patients > 50 are (a) relatives' Extraversion influenced patients' total, interpersonal, and cognitive functioning; (b) relatives' Agreeableness influenced patients' interpersonal functioning; and (c) relatives' Conscientiousness influenced patients' physical HRQoL (ps < .05). Results for patients ≤ 50 are (a) relatives' Neuroticism influenced patients' neurological and emotional functioning, and (b) relatives' Extraversion influenced patients' emotional functioning and psychological HRQoL (ps < .05). The personality traits of the relative covary with the functioning of the patient, and psychological adaptation to the loss of function may progress at a later stage after physical health improvements have been achieved. Thus, a biopsychosocial perspective on the rehabilitation process is needed. © 2016 Wiley Periodicals, Inc.

Prazosin for Prophylaxis of Chronic Post Traumatic Headaches in OEF/OIF/OND Service Members and Veterans with Mild TBI

DTIC Science & Technology

2017-10-01

does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE October 2017 2. REPORT TYPE...comes from a large open-label case series in Iraq and Afghanistan Veterans with mTBI and posttraumatic headaches and data from a placebo- controlled trial...will be accomplished by conducting a randomized placebo- controlled double blind trial of prazosin vs placebo in 160 Iraq/Afghanistan active-duty

Community Reintegration Problems Among Veterans and Active Duty Service Members With Traumatic Brain Injury.

PubMed

McGarity, Suzanne; Barnett, Scott D; Lamberty, Greg; Kretzmer, Tracy; Powell-Cope, Gail; Patel, Nitin; Nakase-Richardson, Risa

To examine community reintegration problems among Veterans and military service members with mild or moderate/severe traumatic brain injury (TBI) at 1 year postinjury and to identify unique predictors that may contribute to these difficulties. VA Polytrauma Rehabilitation Centers. Participants were 154 inpatients enrolled in the VA TBI Model Systems Program with available injury severity data (mild = 28.6%; moderate/severe = 71.4%) and 1-year postinjury outcome data. Prospective, longitudinal cohort. Community reintegration outcomes included independent driving, employability, and general community participation. Additional measures assessed depression, posttraumatic stress, and cognitive and motor functioning. In the mild TBI (mTBI) group, posttraumatic stress disorder and depressive symptoms were associated with lower levels of various community reintegration outcomes. In the moderate/severe TBI group, cognition and motor skills were significantly associated with lower levels of community participation, independent driving, and employability. Community reintegration is problematic for Veterans and active duty service members with a history of TBI. Unique comorbidities across injury severity groups inhibit full reintegration into the community. These findings highlight the ongoing rehabilitation needs of persons with TBI, specifically evidence-based mental healthcare, in comprehensive rehabilitation programs consistent with a chronic disease management model.

A Novel Model of Traumatic Brain Injury in Adult Zebrafish Demonstrates Response to Injury and Treatment Comparable with Mammalian Models.