SU-E-T-812: Volumetric Modulated Arc Therapy-Total Body Irradiation (VMAT-TBI) V.s. Conventional Extended SSD-TBI (cTBI): A Dosimetric Comparisom

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

Ouyang, L; Folkerts, M; Lee, H

2015-06-15

Purpose: To perform a dosimetric evaluation on a new developed volumetric modulated arc therapy based total body irradiation (VMAT-TBI). Methods: Three patients were CT scanned with an indexed rotatable body frame to get whole body CT images. Concatenated CT images were imported in Pinnacle treatment planning system and whole body and lung were contoured as PTV and organ at risk, respectively. Treatment plans were generated by matching multiple isocenter volumetric modulated arc (VMAT) fields of the upper body and multiple isocenter parallel-opposed fields of the lower body. For each plan, 1200 cGy in 8 fractions was prescribed to the wholemore » body volume and the lung dose was constrained to a mean dose of 750 cGy. Such a two-level dose plan was achieved by inverse planning of the torso VMAT fields. For comparison, conventional standing TBI (cTBI) plans were generated on the same whole body CT images at an extended SSD (550cm).The shape of compensators and lung blocks are simulated using body segments and lung contours Compensation was calculated based on the patient CT images, in mimic of the standing TBI treatment. The whole body dose distribution of cTBI plans were calculated with a home-developed GPU Monte Carlo dose engine. Calculated cTBI dose distribution was prescribed to the mid-body point at umbilical level. Results: The VMAT-TBI treatment plans of three patients’ plans achieved 80.2%±5.0% coverage of the total body volume within ±10% of the prescription dose, while cTBI treatment plans achieved 72.2%±4.0% coverage of the total body volume. The averaged mean lung dose of all three patients is lower for VMAT-TBI (7.48 cGy) than for cTBI (8.96 cGy). Conclusion: The proposed patient comfort-oriented VMAT-TBI technique provides for a uniform dose distribution within the total body while reducing the dose to the lungs.« less

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.

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.

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

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.

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.

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.

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

The Sequence of Cyclophosphamide and Myeloablative Total Body Irradiation in Hematopoietic Cell Transplantation for Patients with Acute Leukemia.

PubMed

Holter-Chakrabarty, Jennifer L; Pierson, Namali; Zhang, Mei-Jie; Zhu, Xiaochun; Akpek, Görgün; Aljurf, Mahmoud D; Artz, Andrew S; Baron, Frédéric; Bredeson, Christopher N; Dvorak, Christopher C; Epstein, Robert B; Lazarus, Hillard M; Olsson, Richard F; Selby, George B; Williams, Kirsten M; Cooke, Kenneth R; Pasquini, Marcelo C; McCarthy, Philip L

2015-07-01

Limited clinical data are available to assess whether the sequencing of cyclophosphamide (Cy) and total body irradiation (TBI) changes outcomes. We evaluated the sequence in 1769 (CyTBI, n = 948; TBICy, n = 821) recipients of related or unrelated hematopoietic cell transplantation who received TBI (1200 to 1500 cGY) for acute leukemia from 2003 to 2010. The 2 cohorts were comparable for median age, performance score, type of leukemia, first complete remission, Philadelphia chromosome-positive acute lymphoblastic leukemia, HLA-matched siblings, stem cell source, antithymocyte globulin use, TBI dose, and type of graft-versus-host disease (GVHD) prophylaxis. The sequence of TBI did not significantly affect transplantation-related mortality (24% versus 23% at 3 years, P = .67; relative risk, 1.01; P = .91), leukemia relapse (27% versus 29% at 3 years, P = .34; relative risk, .89, P = .18), leukemia-free survival (49% versus 48% at 3 years, P = .27; relative risk, .93; P = .29), chronic GVHD (45% versus 47% at 1 year, P = .39; relative risk, .9; P = .11), or overall survival (53% versus 52% at 3 years, P = .62; relative risk, .96; P = .57) for CyTBI and TBICy, respectively. Corresponding cumulative incidences of sinusoidal obstruction syndrome were 4% and 6% at 100 days (P = .08), respectively. This study demonstrates that the sequence of Cy and TBI does not impact transplantation outcomes and complications in patients with acute leukemia undergoing hematopoietic cell transplantation with myeloablative conditioning. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

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.

Plasma Anti-Glial Fibrillary Acidic Protein Autoantibody Levels during the Acute and Chronic Phases of Traumatic Brain Injury: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot Study.

PubMed

Wang, Kevin K W; Yang, Zhihui; Yue, John K; Zhang, Zhiqun; Winkler, Ethan A; Puccio, Ava M; Diaz-Arrastia, Ramon; Lingsma, Hester F; Yuh, Esther L; Mukherjee, Pratik; Valadka, Alex B; Gordon, Wayne A; Okonkwo, David O; Manley, Geoffrey T; Cooper, Shelly R; Dams-O'Connor, Kristen; Hricik, Allison J; Inoue, Tomoo; Maas, Andrew I R; Menon, David K; Schnyer, David M; Sinha, Tuhin K; Vassar, Mary J

2016-07-01

We described recently a subacute serum autoantibody response toward glial fibrillary acidic protein (GFAP) and its breakdown products 5-10 days after severe traumatic brain injury (TBI). Here, we expanded our anti-GFAP autoantibody (AutoAb[GFAP]) investigation to the multicenter observational study Transforming Research and Clinical Knowledge in TBI Pilot (TRACK-TBI Pilot) to cover the full spectrum of TBI (Glasgow Coma Scale 3-15) by using acute (<24 h) plasma samples from 196 patients with acute TBI admitted to three Level I trauma centers, and a second cohort of 21 participants with chronic TBI admitted to inpatient TBI rehabilitation. We find that acute patients self-reporting previous TBI with loss of consciousness (LOC) (n = 43) had higher day 1 AutoAb[GFAP] (mean ± standard error: 9.11 ± 1.42; n = 43) than healthy controls (2.90 ± 0.92; n = 16; p = 0.032) and acute patients reporting no previous TBI (2.97 ± 0.37; n = 106; p < 0.001), but not acute patients reporting previous TBI without LOC (8.01 ± 1.80; n = 47; p = 0.906). These data suggest that while exposure to TBI may trigger the AutoAb[GFAP] response, circulating antibodies are elevated specifically in acute TBI patients with a history of TBI. AutoAb[GFAP] levels for participants with chronic TBI (average post-TBI time 176 days or 6.21 months) were also significantly higher (15.08 ± 2.82; n = 21) than healthy controls (p < 0.001). These data suggest a persistent upregulation of the autoimmune response to specific brain antigen(s) in the subacute to chronic phase after TBI, as well as after repeated TBI insults. Hence, AutoAb[GFAP] may be a sensitive assay to study the dynamic interactions between post-injury brain and patient-specific autoimmune responses across acute and chronic settings after TBI.

Outcomes after use of two standard ablative regimens in patients with refractory acute myeloid leukaemia: a retrospective, multicentre, registry analysis.

PubMed

Nagler, Arnon; Savani, Bipin N; Labopin, Myriam; Polge, Emmanuelle; Passweg, Jakob; Finke, Jürgen; Kyrcz-Krzemien, Slawomira; Volin, Liisa; Anagnostopoulos, Achilles; Aljurf, Mahmoud; Beelen, Dietrich W; Vigouroux, Stephane; Milpied, Noel; Suarez, Felipe; Mohty, Mohamad

2015-09-01

Cyclophosphamide plus intravenous busulfan has not been compared with cyclophosphamide plus total body irradiation (TBI) in adults with advanced refractory acute myeloid leukaemia before allogeneic haemopoietic stem-cell transplantation (HCT). We aimed to assess whether survival of patients receiving ablative intravenous busulfan-based conditioning regimens before a related or volunteer-unrelated donor HCT for refractory acute myeloid leukaemia is not inferior to that of patients receiving an ablative TBI-based regimen. In this retrospective, multicentre, registry-based study, we obtained data for patients (aged >18 years) with refractory acute myeloid leukaemia in active phase of disease, who had received HCT from an HLA-identical sibling or an unrelated donor after intravenous busulfan plus cyclophosphamide or cyclophosphamide plus TBI conditioning between 2000 and 2012. Data was obtained from the European Group for Blood and Marrow Transplantation registry. The primary endpoints of the study were overall survival and leukaemia-free survival. We obtained data for 514 patients who had received intravenous busulfan plus cyclophosphamide and 338 patients who had received cyclophosphamide plus TBI. The median percentage of blasts before HCT did not differ significantly between groups (20% [range 5-100; IQR 10-32] in the intravenous busulfan plus cyclophosphamide group vs 16% [5-95; 9-33] in the cyclophosphamide plus TBI group; p=0·16). Overall survival at 2 years did not differ between the groups in the univariate analysis (31·2% [95% CI 26·8-35·5] with intravenous busulfan plus cyclophosphamide vs 33·4% [28·1-38·7] wth cyclophosphamide plus TBI; p=0·65). Leukaemia-free survival at 2 years also did not differ between groups (25·0% [95% CI 21·0-29·0] vs 28·4% [23·4-33·5]; p=0·47). In multivariable analysis adjusting for differences between both groups, no difference was noted between the two groups in terms of overall survival (hazard ratio [HR] 0·99

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

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.

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

PubMed

Kowalski, Robert G; Haarbauer-Krupa, Juliet K; Bell, Jeneita M; Corrigan, John D; Hammond, Flora M; Torbey, Michel T; Hofmann, Melissa C; Dams-O'Connor, Kristen; Miller, A Cate; Whiteneck, Gale G

2017-07-01

Traumatic brain injury (TBI) leads to nearly 300 000 annual US hospitalizations and increased lifetime risk of acute ischemic stroke (AIS). Occurrence of AIS immediately after TBI has not been well characterized. We evaluated AIS acutely after TBI and its impact on outcome. A prospective database of moderate to severe TBI survivors, admitted to inpatient rehabilitation at 22 Traumatic Brain Injury Model Systems centers and their referring acute-care hospitals, was analyzed. Outcome measures were AIS incidence, duration of posttraumatic amnesia, Functional Independence Measure, and Disability Rating Scale, at rehabilitation discharge. Between October 1, 2007, and March 31, 2015, 6488 patients with TBI were enrolled in the Traumatic Brain Injury Model Systems National Database. One hundred and fifty-nine (2.5%) patients had a concurrent AIS, and among these, median age was 40 years. AIS was associated with intracranial mass effect and carotid or vertebral artery dissection. High-velocity events more commonly caused TBI with dissection. AIS predicted poorer outcome by all measures, accounting for a 13.3-point reduction in Functional Independence Measure total score (95% confidence interval, -16.8 to -9.7; P <0.001), a 1.9-point increase in Disability Rating Scale (95% confidence interval, 1.3-2.5; P <0.001), and an 18.3-day increase in posttraumatic amnesia duration (95% confidence interval, 13.1-23.4; P <0.001). Ischemic stroke is observed acutely in 2.5% of moderate to severe TBI survivors and predicts worse functional and cognitive outcome. Half of TBI patients with AIS were aged ≤40 years, and AIS patients more often had cervical dissection. Vigilance for AIS is warranted acutely after TBI, particularly after high-velocity events. © 2017 American Heart Association, Inc.

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.

Prediction of behavioural and cognitive deficits in patients with traumatic brain injury at an acute rehabilitation setting.

PubMed

de Guise, E; LeBlanc, J; Feyz, M; Lamoureux, J; Greffou, S

2017-01-01

The goal of this study was to identify factors that would predict short-term neuropsychological outcome in patients with traumatic brain injury (TBI) hospitalized in an acute rehabilitation setting. Data was collected in the context of an acute early rehabilitation setting of a trauma centre. A brief neuropsychological assessment was carried out for 348 patients within a month following their trauma. Length of post-traumatic amnesia (PTA) was the best predictor of behavioural, memory and executive function variables within a month post TBI. The odds of being agitated, labile, irritable and disinhibited at one month post trauma were almost six times higher for those with PTA that lasted more than 7 days compared to those with a PTA of less than 24 hours. Also, the odds of having a higher mental manipulation score (less significant executive function impairment) were almost two times lower for those with frontal lesions, and three to six times lower for those with PTA of more than 24 hours. In addition, TBI severity, education and age were considered good predictors of some aspects of neuropsychological outcome. This model may help clinicians and administrators recognize the probable post-traumatic deficits as quickly as possible and to plan interventions as well as post-acute discharge orientation accordingly and early on.

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.

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

Effects of total body irradiation-based conditioning on allogeneic stem cell transplantation for pediatric acute leukemia: a single-institution study

PubMed Central

Park, Jongmoo; Choi, Eun Kyung; Kim, Jong Hoon; Lee, Sang-wook; Song, Si Yeol; Yoon, Sang Min; Kim, Young Seok; Kim, Su Ssan; Park, Jin-hong; Park, Jaehyeon

2014-01-01

Purpose To evaluate the effects of total body irradiation (TBI), as a conditioning regimen prior to allogeneic stem cell transplantation (allo-SCT), in pediatric acute leukemia patients. Materials and Methods From January 2001 to December 2011, 28 patients, aged less than 18 years, were treated with TBI-based conditioning for allo-SCT in our institution. Of the 28 patients, 21 patients were diagnosed with acute lymphoblastic leukemia (ALL, 75%) and 7 were diagnosed with acute myeloid leukemia (AML, 25%). TBI was completed 4 days or 1 day before stem cell infusion. Patients underwent radiation therapy with bilateral parallel opposing fields and 6-MV X-rays. The Kaplan-Meier method was used to calculate survival outcomes. Results The 2-year event-free survival and overall survival rates were 66% and 56%, respectively (71.4% and 60.0% in AML patients vs. 64.3% and 52.4% in ALL patients, respectively). Treatment related mortality rate were 25%. Acute and chronic graft-versus-host disease was a major complication; other complications included endocrine dysfunction and pulmonary complications. Common complications from TBI were nausea (89%) and cataracts (7.1%). Conclusion The efficacy and toxicity data in this study of TBI-based conditioning to pediatric acute leukemia patients were comparable with previous studies. However, clinicians need to focus on the acute and chronic complications related to allo-SCT. PMID:25324992

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.

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

Multi-modal magnetic resonance imaging in the acute and sub-acute phase of mild traumatic brain injury: can we see the difference?

PubMed

Toth, Arnold; Kovacs, Noemi; Perlaki, Gabor; Orsi, Gergely; Aradi, Mihaly; Komaromy, Hedvig; Ezer, Erzsebet; Bukovics, Peter; Farkas, Orsolya; Janszky, Jozsef; Doczi, Tamas; Buki, Andras; Schwarcz, Attila

2013-01-01

Advanced magnetic resonance imaging (MRI) methods were shown to be able to detect the subtle structural consequences of mild traumatic brain injury (mTBI). The objective of this study was to investigate the acute structural alterations and recovery after mTBI, using diffusion tensor imaging (DTI) to reveal axonal pathology, volumetric analysis, and susceptibility weighted imaging (SWI) to detect microhemorrhage. Fourteen patients with mTBI who had computed tomography with negative results underwent MRI within 3 days and 1 month after injury. High resolution T1-weighted imaging, DTI, and SWI, were performed at both time points. A control group of 14 matched volunteers were also examined following the same imaging protocol and time interval. Tract-Based Spatial Statistics (TBSS) were performed on DTI data to reveal group differences. T1-weighted images were fed into Freesurfer volumetric analysis. TBSS showed fractional anisotropy (FA) to be significantly (corrected p<0.05) lower, and mean diffusivity (MD) to be higher in the mTBI group in several white matter tracts (FA=40,737; MD=39,078 voxels) compared with controls at 72 hours after injury and still 1month later for FA. Longitudinal analysis revealed significant change (i.e., normalization) of FA and MD over 1 month dominantly in the left hemisphere (FA=3408; MD=7450 voxels). A significant (p<0.05) decrease in cortical volumes (mean 1%) and increase in ventricular volumes (mean 3.4%) appeared at 1 month after injury in the mTBI group. SWI did not reveal microhemorrhage in our patients. Our findings present dynamic micro- and macrostructural changes occurring in the acute to sub-acute phase in mTBI, in very mildly injured patients lacking microhemorrhage detectable by SWI. These results underscore the importance of strictly defined image acquisition time points when performing MRI studies on patients with mTBI.

Comparing Plasma Phospho Tau, Total Tau, and Phospho Tau–Total Tau Ratio as Acute and Chronic Traumatic Brain Injury Biomarkers

PubMed Central

Rubenstein, Richard; Chang, Binggong; Yue, John K.; Chiu, Allen; Winkler, Ethan A.; Puccio, Ava M.; Diaz-Arrastia, Ramon; Yuh, Esther L.; Mukherjee, Pratik; Valadka, Alex B.; Gordon, Wayne A.; Okonkwo, David O.; Davies, Peter; Agarwal, Sanjeev; Lin, Fan; Sarkis, George; Yadikar, Hamad; Yang, Zhihui; Manley, Geoffrey T.; Wang, Kevin K. W.

2017-01-01

IMPORTANCE Annually in the United States, at least 3.5 million people seek medical attention for traumatic brain injury (TBI). The development of therapies for TBI is limited by the absence of diagnostic and prognostic biomarkers. Microtubule-associated protein tau is an axonal phosphoprotein. To date, the presence of the hypophosphorylated tau protein (P-tau) in plasma from patients with acute TBI and chronic TBI has not been investigated. OBJECTIVE To examine the associations between plasma P-tau and total-tau (T-tau) levels and injury presence, severity, type of pathoanatomic lesion (neuroimaging), and patient outcomes in acute and chronic TBI. DESIGN, SETTING, AND PARTICIPANTS In the TRACK-TBI Pilot study, plasma was collected at a single time point from 196 patients with acute TBI admitted to 3 level I trauma centers (<24 hours after injury) and 21 patients with TBI admitted to inpatient rehabilitation units (mean [SD], 176.4 [44.5] days after injury). Control samples were purchased from a commercial vendor. The TRACK-TBI Pilot study was conducted from April 1, 2010, to June 30, 2012. Data analysis for the current investigation was performed from August 1, 2015, to March 13, 2017. MAIN OUTCOMES AND MEASURES Plasma samples were assayed for P-tau (using an antibody that specifically recognizes phosphothreonine-231) and T-tau using ultra-high sensitivity laser-based immunoassay multi-arrayed fiberoptics conjugated with rolling circle amplification. RESULTS In the 217 patients with TBI, 161 (74.2%) were men; mean (SD) age was 42.5 (18.1) years. The P-tau and T-tau levels and P-tau–T-tau ratio in patients with acute TBI were higher than those in healthy controls. Receiver operating characteristic analysis for the 3 tau indices demonstrated accuracy with area under the curve (AUC) of 1.000, 0.916, and 1.000, respectively, for discriminating mild TBI (Glasgow Coma Scale [GCS] score, 13–15, n = 162) from healthy controls. The P-tau level and P-tau–T-tau ratio

Comparing Plasma Phospho Tau, Total Tau, and Phospho Tau-Total Tau Ratio as Acute and Chronic Traumatic Brain Injury Biomarkers.

PubMed

Rubenstein, Richard; Chang, Binggong; Yue, John K; Chiu, Allen; Winkler, Ethan A; Puccio, Ava M; Diaz-Arrastia, Ramon; Yuh, Esther L; Mukherjee, Pratik; Valadka, Alex B; Gordon, Wayne A; Okonkwo, David O; Davies, Peter; Agarwal, Sanjeev; Lin, Fan; Sarkis, George; Yadikar, Hamad; Yang, Zhihui; Manley, Geoffrey T; Wang, Kevin K W; Cooper, Shelly R; Dams-O'Connor, Kristen; Borrasso, Allison J; Inoue, Tomoo; Maas, Andrew I R; Menon, David K; Schnyer, David M; Vassar, Mary J

2017-09-01

Annually in the United States, at least 3.5 million people seek medical attention for traumatic brain injury (TBI). The development of therapies for TBI is limited by the absence of diagnostic and prognostic biomarkers. Microtubule-associated protein tau is an axonal phosphoprotein. To date, the presence of the hypophosphorylated tau protein (P-tau) in plasma from patients with acute TBI and chronic TBI has not been investigated. To examine the associations between plasma P-tau and total-tau (T-tau) levels and injury presence, severity, type of pathoanatomic lesion (neuroimaging), and patient outcomes in acute and chronic TBI. In the TRACK-TBI Pilot study, plasma was collected at a single time point from 196 patients with acute TBI admitted to 3 level I trauma centers (<24 hours after injury) and 21 patients with TBI admitted to inpatient rehabilitation units (mean [SD], 176.4 [44.5] days after injury). Control samples were purchased from a commercial vendor. The TRACK-TBI Pilot study was conducted from April 1, 2010, to June 30, 2012. Data analysis for the current investigation was performed from August 1, 2015, to March 13, 2017. Plasma samples were assayed for P-tau (using an antibody that specifically recognizes phosphothreonine-231) and T-tau using ultra-high sensitivity laser-based immunoassay multi-arrayed fiberoptics conjugated with rolling circle amplification. In the 217 patients with TBI, 161 (74.2%) were men; mean (SD) age was 42.5 (18.1) years. The P-tau and T-tau levels and P-tau-T-tau ratio in patients with acute TBI were higher than those in healthy controls. Receiver operating characteristic analysis for the 3 tau indices demonstrated accuracy with area under the curve (AUC) of 1.000, 0.916, and 1.000, respectively, for discriminating mild TBI (Glasgow Coma Scale [GCS] score, 13-15, n = 162) from healthy controls. The P-tau level and P-tau-T-tau ratio were higher in individuals with more severe TBI (GCS, ≤12 vs 13-15). The P-tau level and P

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.

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.

TBI-ROC Part Six: Lifelong Living after TBI

ERIC Educational Resources Information Center

Boeing, Marianne; Barton, Barbara; Zinsmeister, Paula; Brouwers, Lynn; Trudel, Tina M.; Elias, Eileen; Weider, Katie

2010-01-01

This article is the sixth of a multi-part series on traumatic brain injury (TBI) and discusses lifelong living after TBI. Following TBI, lifelong outcomes vary depending on the individual affected, treatment provided and severity of injury. Fortunately, many individuals who experience mild concussions common to childhood have no lasting symptoms.…

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.

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.

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:

Prospective investigation of anterior pituitary function in the acute phase and 12 months after pediatric traumatic brain injury.

PubMed

Ulutabanca, Halil; Hatipoglu, Nihal; Tanriverdi, Fatih; Gökoglu, Abdülkerim; Keskin, Mehmet; Selcuklu, Ahmet; Kurtoglu, Selim; Kelestimur, Fahrettin

2014-06-01

Although head trauma is common in childhood, there is no enough prospective study investigating both acute phase and 12 months after injury. Therefore, a prospective clinical trial was planned to evaluate the pituitary function in childhood in the acute and chronic phase after traumatic brain injury (TBI). Forty-one children (27 boys and 14 girls, mean age 7 ± 4.3), who were admitted to neurosurgery intensive care unit due to head trauma, were included. Twenty-one (51.2 %) patients had mild, 10 (24.4 %) had moderate, and 10 (24.4 %) had severe TBI. Twenty-two of them were reevaluated 12 months after TBI. Basal pituitary hormone levels were measured during acute (first 24 h) and chronic phase of TBI. Additionally, in the chronic phase, GHRH-arginine test was used for the diagnosis of growth hormone (GH) deficiency. In the acute phase, 10 patients (24.4 %) had ACTH deficiency, and the overall 44.3 % of patients had at least one pituitary hormone dysfunction. All the pituitary hormone deficiencies during the acute phase were recovered after 12 months. Two patients (9.1 %) had new-onset GH deficiency in the chronic phase, and in one of them, ACTH deficiency was also present. Present prospective data clearly demonstrated that most of the hormonal changes in the early acute phase were transient, suggesting an adaptive response, and these changes did not predict the hormone deficiencies after 1 year. In the chronic phase, although GH deficiency was present, the frequency of TBI-induced hypopituitarism was clearly lower than the adult patients.

Cortisol evaluation during the acute phase of traumatic brain injury-A prospective study.

PubMed

Bensalah, Meriem; Donaldson, Malcolm; Aribi, Yamina; Iabassen, Malek; Cherfi, Lyes; Nebbal, Mustapha; Medjaher, Meriem; Haffaf, ElMehdi; Abdennebi, Benaissa; Guenane, Kamel; Djermane, Adel; Kemali, Zahra; OuldKablia, Samia

2018-05-01

Biochemical diagnosis of adrenal insufficiency (AI) is difficult in the context of traumatic brain injury (TBI). To assess the frequency and predictive factors of AI in victims of TBI from Algiers. Between November 2009 and December 2013, TBI victims had a single 8-9 am serum cortisol measurement during the acute postinjury period (0-7 days). AI was defined according to basal cortisol levels of 83, 276 and 414 nmol/L. Variables studied were TBI severity according to Glasgow coma scale, duration of intubation and coma, pupillary status, hypotension, anaemia, brain imaging findings, diabetes insipidus and medication. Insulin tolerance test was performed during the recovery phase, defining AI as peak cortisol <500 nmol/L. Cortisol samples were obtained at median 3 (1-7) days from 277 patients (257M: 20F) aged 32 (18-65) years. Acute AI frequency was 8 (2.8%), 20 (21%) and 35 (37%), respectively using the three cortisol cut-offs. Factors predicting AI were diastolic hypotension, sedative medication, diabetes insipidus, skull base fracture and intraparenchymal haematoma. Mortality was highest in patients with acute cortisol <276 nmol/L (44.6% with OR for death 1.64, 95% CI 0.92-3.0, P = .12). During the recovery phase, AI was present in 3 of 3, 12 of 24, 4 of 16 and 20 of 66 patients with week 1 cortisol <83, 83-276, 277-414 and >414 nmol/L. Hydrocortisone replacement is advised in TBI patients with morning cortisol <276 nmol/L or those <414 nmol/L with additional risk factors for AI. As acute and subsequent AI are poorly correlated, patients with moderate/severe TBI require adrenal re-evaluation during the recovery phase. © 2018 John Wiley & Sons Ltd.

Combined SCI and TBI: Recovery of forelimb function after unilateral cervical spinal cord injury (SCI) is retarded by contralateral traumatic brain injury (TBI), and ipsilateral TBI balances the effects of SCI on paw placement

PubMed Central

Inoue, Tomoo; Lin, Amity; Ma, Xiaokui; McKenna, Stephen L.; Creasey, Graham H.; Manley, Geoffrey T.; Ferguson, Adam R.; Bresnahan, Jacqueline C.; Beattie, Michael S.

2015-01-01

A significant proportion (estimates range from 16–74%) of patients with spinal cord injury (SCI) have concomitant traumatic brain injury (TBI), and the combination often produces difficulties in planning and implementing rehabilitation strategies and drug therapies. For example, many of the drugs used to treat SCI may interfere with cognitive rehabilitation, and conversely drugs that are used to control seizures in TBI patients may undermine locomotor recovery after SCI. The current paper presents an experimental animal model for combined SCI and TBI to help drive mechanistic studies of dual diagnosis. Rats received a unilateral SCI (75 kdyn) at C5 vertebral level, a unilateral TBI (2.0 mm depth, 4.0 m/s velocity impact on the forelimb sensori-motor cortex), or both SCI + TBI. TBI was placed either contralateral or ipsilateral to the SCI. Behavioral recovery was examined using paw placement in a cylinder, grooming, open field locomotion, and the IBB cereal eating test. Over 6 weeks, in the paw placement test, SCI + contralateral TBI produced a profound deficit that failed to recover, but SCI + ipsilateral TBI increased the relative use of the paw on the SCI side. In the grooming test, SCI + contralateral TBI produced worse recovery than either lesion alone even though contralateral TBI alone produced no observable deficit. In the IBB forelimb test, SCI + contralateral TBI revealed a severe deficit that recovered in 3 weeks. For open field locomotion, SCI alone or in combination with TBI resulted in an initial deficit that recovered in 2 weeks. Thus, TBI and SCI affected forelimb function differently depending upon the test, reflecting different neural substrates underlying, for example, exploratory paw placement and stereotyped grooming. Concurrent SCI and TBI had significantly different effects on outcomes and recovery, depending upon laterality of the two lesions. Recovery of function after cervical SCI was retarded by the addition of a moderate TBI in the

Combined SCI and TBI: recovery of forelimb function after unilateral cervical spinal cord injury (SCI) is retarded by contralateral traumatic brain injury (TBI), and ipsilateral TBI balances the effects of SCI on paw placement.

PubMed

Inoue, Tomoo; Lin, Amity; Ma, Xiaokui; McKenna, Stephen L; Creasey, Graham H; Manley, Geoffrey T; Ferguson, Adam R; Bresnahan, Jacqueline C; Beattie, Michael S

2013-10-01

A significant proportion (estimates range from 16 to 74%) of patients with spinal cord injury (SCI) have concomitant traumatic brain injury (TBI), and the combination often produces difficulties in planning and implementing rehabilitation strategies and drug therapies. For example, many of the drugs used to treat SCI may interfere with cognitive rehabilitation, and conversely drugs that are used to control seizures in TBI patients may undermine locomotor recovery after SCI. The current paper presents an experimental animal model for combined SCI and TBI to help drive mechanistic studies of dual diagnosis. Rats received a unilateral SCI (75 kdyn) at C5 vertebral level, a unilateral TBI (2.0 mm depth, 4.0 m/s velocity impact on the forelimb sensori-motor cortex), or both SCI+TBI. TBI was placed either contralateral or ipsilateral to the SCI. Behavioral recovery was examined using paw placement in a cylinder, grooming, open field locomotion, and the IBB cereal eating test. Over 6weeks, in the paw placement test, SCI+contralateral TBI produced a profound deficit that failed to recover, but SCI+ipsilateral TBI increased the relative use of the paw on the SCI side. In the grooming test, SCI+contralateral TBI produced worse recovery than either lesion alone even though contralateral TBI alone produced no observable deficit. In the IBB forelimb test, SCI+contralateral TBI revealed a severe deficit that recovered in 3 weeks. For open field locomotion, SCI alone or in combination with TBI resulted in an initial deficit that recovered in 2 weeks. Thus, TBI and SCI affected forelimb function differently depending upon the test, reflecting different neural substrates underlying, for example, exploratory paw placement and stereotyped grooming. Concurrent SCI and TBI had significantly different effects on outcomes and recovery, depending upon laterality of the two lesions. Recovery of function after cervical SCI was retarded by the addition of a moderate TBI in the contralateral

Telerehabilitation for Veterans with Combat Related TBI/PTSD

DTIC Science & Technology

2011-04-01

unnecessary sheering forces and edema. Some patients with TBI also have SCI that may result in pressure ulcers . 1.1 Conceptual Model The conceptual...appointments with specialists, medication management and compliance, counseling, education and monitoring outcomes. The ARNP coordinates care for TBI...coordination Drug therapy: Drugs are frequently used in the management common of complications of polytrauma such as TBI particularly for mood

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

TBI-ROC Part Nine: Diagnosing TBI and Psychiatric Disorders

ERIC Educational Resources Information Center

Elias, Eileen; Weider, Katie; Mustafa, Ruman

2011-01-01

This article is the ninth of a multi-part series on traumatic brain injury (TBI). It focuses on the process of diagnosing TBI and psychiatric disorders. Diagnosing traumatic brain injury can be challenging. It can be difficult differentiating TBI and psychiatric symptoms, as both have similar symptoms (e.g., memory problems, emotional outbursts,…

Inflammatory cytokine and chemokine profiles are associated with patient outcome and the hyperadrenergic state following acute brain injury.

PubMed

Di Battista, Alex P; Rhind, Shawn G; Hutchison, Michael G; Hassan, Syed; Shiu, Maria Y; Inaba, Kenji; Topolovec-Vranic, Jane; Neto, Antonio Capone; Rizoli, Sandro B; Baker, Andrew J

2016-02-16

Traumatic brain injury (TBI) elicits intense sympathetic nervous system (SNS) activation with profuse catecholamine secretion. The resultant hyperadrenergic state is linked to immunomodulation both within the brain and systemically. Dysregulated inflammation post-TBI exacerbates secondary brain injury and contributes to unfavorable patient outcomes including death. The aim of this study was to characterize the early dynamic profile of circulating inflammatory cytokines/chemokines in patients admitted for moderate-to-severe TBI, to examine interrelationships between these mediators and catecholamines, as well as clinical indices of injury severity and neurological outcome. Blood was sampled from 166 isolated TBI patients (aged 45 ± 20.3 years; 74.7 % male) on admission, 6-, 12-, and 24-h post-injury and from healthy controls (N = 21). Plasma cytokine [interleukin (IL)-1β, -2, -4, -5, -10, -12p70, -13, tumor necrosis factor (TNF)-α, interferon (IFN)-γ] and chemokine [IL-8, eotaxin, eotaxin-3, IFN-γ-induced protein (IP)-10, monocyte chemoattractant protein (MCP)-1, -4, macrophage-derived chemokine (MDC), macrophage inflammatory protein (MIP)-1β, thymus activation regulated chemokine (TARC)] concentrations were analyzed using high-sensitivity electrochemiluminescence multiplex immunoassays. Plasma catecholamines [epinephrine (Epi), norepinephrine (NE)] were measured by immunoassay. Neurological outcome at 6 months was assessed using the extended Glasgow outcome scale (GOSE) dichotomized as good (>4) or poor (≤4) outcomes. Patients showed altered levels of IL-10 and all chemokines assayed relative to controls. Significant differences in a number of markers were evident between moderate and severe TBI cohorts. Elevated IL-8, IL-10, and TNF-α, as well as alterations in 8 of 9 chemokines, were associated with poor outcome at 6 months. Notably, a positive association was found between Epi and IL-1β, IL-10, Eotaxin, IL-8, and MCP-1. NE was positively associated

Growth impairment after TBI of leukemia survivors children: a model- based investigation.

PubMed

Galletto, Chiara; Gliozzi, Antonio; Nucera, Daniele; Bertorello, Nicoletta; Biasin, Eleonora; Corrias, Andrea; Chiabotto, Patrizia; Fagioli, Franca; Guiot, Caterina

2014-10-13

Children receiving Total Body Irradiation (TBI) in preparation for Hematopoietic Stem Cell Transplantation (HSCT) are at risk for Growth Hormone Deficiency (GHD), which sometimes severely compromises their Final Height (FH). To better represent the impact of such therapies on growth we apply a mathematical model, which accounts both for the gompertzian-like growth trend and the hormone-related 'spurts', and evaluate how the parameter values estimated on the children undergoing TBI differ from those of the matched normal population. 25 patients long-term childhood lymphoblastic and myeloid acute leukaemia survivors followed at Pediatric Onco-Hematology, Stem Cell Transplantation and Cellular Therapy Division, Regina Margherita Children's Hospital (Turin, Italy) were retrospectively analysed for assessing the influence of TBI on their longitudinal growth and for validating a new method to estimate the GH therapy effects. Six were treated with GH therapy after a GHD diagnosis. We show that when TBI was performed before puberty overall growth and pubertal duration were significantly impaired, but such growth limitations were completely reverted in the small sample (6 over 25) of children who underwent GH replacement therapies. Since in principle the model could account for any additional growth 'spurt' induced by therapy, it may become a useful 'simulation' tool for paediatricians for comparing the predicted therapy effectiveness depending on its timing and dosage.

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

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.

Electroencephalographic inverse localization of brain activity in acute traumatic brain injury as a guide to surgery, monitoring and treatment

PubMed Central

Irimia, Andrei; Goh, S.-Y. Matthew; Torgerson, Carinna M.; Stein, Nathan R.; Chambers, Micah C.; Vespa, Paul M.; Van Horn, John D.

2013-01-01

Objective To inverse-localize epileptiform cortical electrical activity recorded from severe traumatic brain injury (TBI) patients using electroencephalography (EEG). Methods Three acute TBI cases were imaged using computed tomography (CT) and multimodal magnetic resonance imaging (MRI). Semi-automatic segmentation was performed to partition the complete TBI head into 25 distinct tissue types, including 6 tissue types accounting for pathology. Segmentations were employed to generate a finite element method model of the head, and EEG activity generators were modeled as dipolar currents distributed over the cortical surface. Results We demonstrate anatomically faithful localization of EEG generators responsible for epileptiform discharges in severe TBI. By accounting for injury-related tissue conductivity changes, our work offers the most realistic implementation currently available for the inverse estimation of cortical activity in TBI. Conclusion Whereas standard localization techniques are available for electrical activity mapping in uninjured brains, they are rarely applied to acute TBI. Modern models of TBI-induced pathology can inform the localization of epileptogenic foci, improve surgical efficacy, contribute to the improvement of critical care monitoring and provide guidance for patient-tailored treatment. With approaches such as this, neurosurgeons and neurologists can study brain activity in acute TBI and obtain insights regarding injury effects upon brain metabolism and clinical outcome. PMID:24011495

Electroencephalographic inverse localization of brain activity in acute traumatic brain injury as a guide to surgery, monitoring and treatment.

PubMed

Irimia, Andrei; Goh, S-Y Matthew; Torgerson, Carinna M; Stein, Nathan R; Chambers, Micah C; Vespa, Paul M; Van Horn, John D

2013-10-01

To inverse-localize epileptiform cortical electrical activity recorded from severe traumatic brain injury (TBI) patients using electroencephalography (EEG). Three acute TBI cases were imaged using computed tomography (CT) and multimodal magnetic resonance imaging (MRI). Semi-automatic segmentation was performed to partition the complete TBI head into 25 distinct tissue types, including 6 tissue types accounting for pathology. Segmentations were employed to generate a finite element method model of the head, and EEG activity generators were modeled as dipolar currents distributed over the cortical surface. We demonstrate anatomically faithful localization of EEG generators responsible for epileptiform discharges in severe TBI. By accounting for injury-related tissue conductivity changes, our work offers the most realistic implementation currently available for the inverse estimation of cortical activity in TBI. Whereas standard localization techniques are available for electrical activity mapping in uninjured brains, they are rarely applied to acute TBI. Modern models of TBI-induced pathology can inform the localization of epileptogenic foci, improve surgical efficacy, contribute to the improvement of critical care monitoring and provide guidance for patient-tailored treatment. With approaches such as this, neurosurgeons and neurologists can study brain activity in acute TBI and obtain insights regarding injury effects upon brain metabolism and clinical outcome. Published by Elsevier B.V.

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.

Hypogonadotrophism fails to prevent severe testicular damage induced by total body irradiation in a patient with beta-thalassaemia major and acute lymphoblastic leukaemia.

PubMed

Chatterjee, R; Kottaridis, P D; McGarrigle, H H; Papatryphonos, A; Goldstone, A H

2001-11-01

Radiation and chemotherapeutic drugs for cancer produce prolonged and often irreversible gonadal damage. To determine whether total body irradiation (TBI)-induced gonadal damage can be prevented by suppression of pituitary gonadotrophin levels, we studied a patient with transfusion dependent homozygous beta-thalassaemia and acute lymphoblastic leukaemia (ALL) who underwent one-antigen mismatched related bone marrow transplantation (BMT). Our data showed that despite having hypogonadotrophic hypogonadism (HH) prior to BMT, the patient developed primary testicular failure following the procedure, indicating that hypogonadotrophism failed to offer protection against TBI-induced testicular damage in this patient. Although this is an interesting case report, no firm conclusions can be drawn from a single patient.

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.

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

Plasma cytokines IL-6, IL-8, and IL-10 are associated with the development of acute respiratory distress syndrome in patients with severe traumatic brain injury.

PubMed

Aisiku, Imo P; Yamal, Jose-Miguel; Doshi, Pratik; Benoit, Julia S; Gopinath, Shankar; Goodman, Jerry C; Robertson, Claudia S

2016-09-15

Patients with severe traumatic brain injury (TBI) are at risk of the development of acute respiratory distress syndrome (ARDS). TBI and ARDS pathophysiologic mechanisms are known to independently involve significant inflammatory responses. The literature on the association between plasma inflammatory cytokines and ARDS in patients with TBI is sparse. The study was a secondary analysis of the safety of a randomized trial of erythropoietin and transfusion threshold in patients with severe TBI. Inflammatory markers within the first 24 hours after injury were compared in patients who developed ARDS and patients without ARDS, using Cox proportional hazards models. There were 200 patients enrolled in the study. The majority of plasma and cerebrospinal fluid (CSF) cytokine levels were obtained within 6 hours. Plasma proinflammatory markers IL-6 and IL-8 and anti-inflammatory marker IL-10 were associated with the development of ARDS (adjusted hazard ratio (HR) = 1.55, confidence interval (CI) = 1.14, 2.11, P = 0.005 for IL-6; adjusted HR = 1.32, CI = 1.10, 1.59, P = 0.003 for IL-8). Plasma markers of IL-6, IL-8, and IL-10 are associated with ARDS in patients with severe TBI. NCT00313716 registered 4/2006.

Comparative study on skin dose measurement using MOSFET and TLD for pediatric patients with acute lymphatic leukemia.

PubMed

Al-Mohammed, Huda I; Mahyoub, Fareed H; Moftah, Belal A

2010-07-01

The object of this study was to compare the difference of skin dose measured in patients with acute lymphatic leukemia (ALL) treated with total body irradiation (TBI) using metal oxide semiconductor field-effect transistors (mobile MOSFET dose verification system (TN-RD-70-W) and thermoluminescent dosimeters (TLD-100 chips, Harshaw/ Bicron, OH, USA). Because TLD has been the most-commonly used technique in the skin dose measurement of TBI, the aim of the present study is to prove the benefit of using the mobile MOSFET (metal oxide semiconductor field effect transistor) dosimeter, for entrance dose measurements during the total body irradiation (TBI) over thermoluminescent dosimeters (TLD). The measurements involved 10 pediatric patients ages between 3 and 14 years. Thermoluminescent dosimeters and MOSFET dosimetry were performed at 9 different anatomic sites on each patient. The present results show there is a variation between skin dose measured with MOSFET and TLD in all patients, and for every anatomic site selected, there is no significant difference in the dose delivered using MOSFET as compared to the prescribed dose. However, there is a significant difference for every anatomic site using TLD compared with either the prescribed dose or MOSFET. The results indicate that the dosimeter measurements using the MOSFET gave precise measurements of prescribed dose. However, TLD measurement showed significant increased skin dose of cGy as compared to either prescribed dose or MOSFET group. MOSFET dosimeters provide superior dose accuracy for skin dose measurement in TBI as compared with TLD.

Pituitary dysfunction in traumatic brain injury: Is evaluation in the acute phase worthwhile?

PubMed Central

Dalwadi, Pradip P.; Bhagwat, Nikhil M.; Tayde, Parimal S.; Joshi, Ameya S.; Varthakavi, Premlata K.

2017-01-01

Introduction: Traumatic brain injury (TBI) is an under-recognized cause of hypopituitarism. According to recent data, it could be more frequent than previously known. However, there is a scarcity of data in Indian population. Aims: The main aim of the study was to determine the prevalence of pituitary hormone deficiencies in the acute phase of TBI. The secondary objectives were to correlate the severity of trauma with basal hormone levels and to determine whether initial hormone deficiencies predict mortality. Subjects and Methods: Forty-nine TBI patients (41 men and 8 women) were included in this study. Pituitary functions were evaluated within 24 h of admission. Results: Gonadotropin deficiency was found in 65.3% patient while 46.9% had low insulin-like growth factor-1, 12.24% had cortisol level <7 mcg/dl. Cortisol and prolactin level were positively correlated with the severity of TBI suggestive of stress response. Free triiodothyronine (fT3) and free thyroxine were significantly lower in patients with increasing severity of tuberculosis. Logistic regression analysis revealed that mortality after TBI was unrelated to the basal pituitary hormone levels except low T3 level, which was found to be positively related to mortality. Conclusions: Pituitary dysfunction is common after TBI and the most commonly affected axes are growth hormone and gonadotropin axis. Low fT3 correlates best with mortality. During the acute phase of TBI, at least an assessment of cortisol is vital as undetected cortisol deficiency can be life-threatening PMID:28217503

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

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.

Characteristics of acute treatment costs of traumatic brain injury in Eastern China--a multi-centre prospective observational study.

PubMed

Yuan, Qiang; Liu, Hua; Wu, Xing; Sun, Yirui; Yao, Haijun; Zhou, Liangfu; Hu, Jin

2012-12-01

This study investigated acute treatment costs and related factors for traumatic brain injuries (TBI) in eastern China based on a prospective multicentre study. Data were prospectively collected from 80 hospitals in eastern China by standardized structured questionnaires during 2004. Included patients were admitted to hospitals via an emergency service with a diagnosis of TBI. The total acute hospitalization treatment costs derived from unsubsidized total hospital billings were used as the main outcome measure. Univariate and multivariable regression models were used to examine factors associated with each outcome. In total, 13,007 TBI cases were identified from 80 hospitals in eastern China. The median cost per hospitalization was $879 US (range, $72-45,894). The median cost per day was $79 (interquartile range, $49-126). The hospitalization costs varied based on the cause of TBI, with a median of $1017 for traffic accidents, $816 for falls, $490 for blows to the head, and $712 for falls. The hospitalization costs also varied by injury type with a mean of $918 for TBI associated with other injuries and $831 for isolated TBI. Using multiple regression analyses, lower admission Glasgow Coma score, longer hospital stay (LOS), male sex, transient patient status, traffic accident, injury occurring on a construction site, treatment at a tertiary hospital, neurosurgical intensive care unit (NICU) or ICU stay, associated polytrauma, and those who needed a neurosurgical operation had significantly higher total acute hospitalization costs than those of other groups. Good recovery and self-paying patients had lower total costs. A double LOS was associated with a 1.61 (95% confidence interval, 1.59-1.62) times higher hospital cost. Our results have potential implications for health-care resource planning during TBI treatment. Measures to prevent traffic accidents and reduce the LOS may help to reduce acute hospitalization costs. Crown Copyright © 2012. Published by Elsevier

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

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

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.

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.

Acute Management of Hemostasis in Patients With Neurological Injury.

PubMed

Baharoglu, M Irem; Brand, Anneke; Koopman, Maria M; Vermeulen, Marinus; Roos, Yvo B W E M

2017-10-01

Neurological injuries can be divided into those with traumatic and nontraumatic causes. The largest groups are traumatic brain injury (TBI) and nontraumatic stroke. TBI patients may present with intracranial hemorrhages (contusions, or subdural or epidural hematomas). Strokes are ischemic or hemorrhagic. In all these disorders, thrombosis and hemostasis play a major role. Treatment aims to either cease bleeding and/or restore perfusion. We reviewed hemostatic and thrombolytic therapies in patients with neurological injuries by MEDLINE and EMBASE search using various key words for neurological disorders and hemostatic therapies restricted to English language and human adults. Review of articles fulfilling inclusion criteria and relevant references revealed that, in patients with ischemic stroke, intravenous thrombolytic therapy with recombinant tissue plasminogen activator within 4.5-5 hours after onset of symptoms improves clinical outcome. In contrast, there are no hemostatic therapies that are proven to improve clinical outcome of patients with hemorrhagic stroke or TBI. In patients with hemorrhagic stroke who use vitamin K antagonist or direct oral anticoagulants, there is evidence that specific reversal therapies improve hemostatic laboratory parameters but without an effect on clinical recovery. In patients with hemorrhagic stroke or TBI who use concomitant antiplatelet therapy, there is evidence for harm of platelet transfusion. In patients with aneurysmal subarachnoid hemorrhage, tranexamic acid was shown to reduce rebleeding rate without improving clinical outcome. The effects of tranexamic acid in patients with TBI are still under investigation. We conclude that, in patients with ischemic stroke, thrombolytic therapy improves outcome when given within 4.5-5 hours. In hemorrhagic stroke and TBI, most hemostatic therapies improved or corrected laboratory parameters but not clinical outcome. Currently, in several trials, the effects of tranexamic acid are

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.

Brain and Plasma Molecular Characterization of the Pathogenic TBI-AD Interrelationship in Mouse Models

DTIC Science & Technology

2015-10-01

collegiate football players: the NCAA Concussion Study. JAMA 290, 2549-2555. Hinkebein, J.H., Martin, T.A., Callahan, C.D., and Johnstone, B. (2003). Concept...al., 2014). We have also developed a novel mouse model of mild TBI (mTBI)/ concussion in which we have demonstrated cognitive dysfunction at 6, 12...2010). Boxing-acute complications and late sequelae: from concussion to dementia. Dtsch Arztebl Int 107, 835-839. Gaetz, M., and Weinberg, H

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

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.

Impact of acute lung injury and acute respiratory distress syndrome after traumatic brain injury in the United States.

PubMed

Rincon, Fred; Ghosh, Sayantani; Dey, Saugat; Maltenfort, Mitchell; Vibbert, Matthew; Urtecho, Jacqueline; McBride, William; Moussouttas, Michael; Bell, Rodney; Ratliff, John K; Jallo, Jack

2012-10-01

Traumatic brain injury (TBI) is a major cause of disability, morbidity, and mortality. The effect of the acute respiratory distress syndrome and acute lung injury (ARDS/ALI) on in-hospital mortality after TBI remains controversial. To determine the epidemiology of ARDS/ALI, the prevalence of risk factors, and impact on in-hospital mortality after TBI in the United States. Retrospective cohort study of admissions of adult patients>18 years with a diagnosis of TBI and ARDS/ALI from 1988 to 2008 identified through the Nationwide Inpatient Sample. During the 20-year study period, the prevalence of ARDS/ALI increased from 2% (95% confidence interval [CI], 2.1%-2.4%) in 1988 to 22% (95% CI, 21%-22%) in 2008 (P<.001). ARDS/ALI was more common in younger age; males; white race; later year of admission; in conjunction with comorbidities such as congestive heart failure, hypertension, chronic obstructive pulmonary disease, chronic renal and liver failure, sepsis, multiorgan dysfunction; and nonrural, medium/large hospitals, located in the Midwest, South, and West continental US location. Mortality after TBI decreased from 13% (95% CI, 12%-14%) in 1988 to 9% (95% CI, 9%-10%) in 2008 (P<.001). ARDS/ALI-related mortality after TBI decreased from 33% (95% CI, 33%-34%) in 1988 to 28% (95% CI, 28%-29%) in 2008 (P<.001). Predictors of in-hospital mortality after TBI were older age, male sex, white race, cancer, chronic kidney disease, hypertension, chronic liver disease, congestive heart failure, ARDS/ALI, and organ dysfunctions. Our analysis demonstrates that ARDS/ALI is common after TBI. Despite an overall reduction of in-hospital mortality, ARDS/ALI carries a higher risk of in-hospital death after TBI.

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

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

Thiotepa-based conditioning versus total body irradiation as myeloablative conditioning prior to allogeneic stem cell transplantation for acute lymphoblastic leukemia: A matched-pair analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

PubMed

Eder, Sandra; Canaani, Jonathan; Beohou, Eric; Labopin, Myriam; Sanz, Jaime; Arcese, William; Or, Reuven; Finke, Juergen; Cortelezzi, Agostino; Beelen, Dietrich; Passweg, Jakob; Socié, Gerard; Gurman, Gunhan; Aljurf, Mahmoud; Stelljes, Matthias; Giebel, Sebastian; Mohty, Mohamad; Nagler, Arnon

2017-10-01

The optimal conditioning regimen to employ before hematopoietic stem cell transplantation in acute lymphoblastic leukemia (ALL) is still undecided, and while cyclophosphamide/total body irradiation (Cy/TBI) is the most commonly used myeloablative regimen, there are concerns regarding long-term toxicity for patients conditioned with this regimen. Thiotepa-based conditioning is an emerging radiation-free regimen with recent publications indicative of comparable clinical outcomes to TBI-based conditioning. In this analysis of the acute leukemia working party of the EBMT, we performed a retrospective matched-pair analysis, evaluating the outcome of adult patients with ALL who received thiotepa-based conditioning (n = 180) with those receiving Cy/TBI conditioning (n = 540). The 2-year leukemia-free survival and overall survival (OS) rates of both conditioning regimens were comparable, 33% for thiotepa [95% confidence interval (CI): 26.4-42.8] versus 39% for Cy/TBI (95% CI: 34.8-44.5] (P = .33) and 46.5% [95% CI: 38.6-56.1] versus 48.8% [95% CI: 44.2-54] (P = .9), respectively. There was no significant difference between the two regimens in the incidence of either acute graft versus host disease (GVHD) or chronic GVHD. Multivariate analysis demonstrated increased relapse incidence for thiotepa conditioning compared to Cy/TBI (HR = 1.78, 95% CI, 1.07-2.95; P = .03) which did not affect OS. Our results indicate that thiotepa-based conditioning may not be inferior to Cy/TBI for adult patients with ALL. © 2017 Wiley Periodicals, Inc.

Psychological Characteristics in Acute Mild Traumatic Brain Injury: An MMPI-2 Study.

PubMed

Gass, Carlton S; Rogers, David; Kinne, Erica

2017-01-01

The psychological characteristics of acute traumatic brain injury (TBI) have received limited research focus, despite empirical evidence of their relevance for subsequent psychological adjustment and early therapeutic intervention. This study addressed a wide range of psychological features in 47 individuals who were hospitalized as a result of acute mild TBI (mTBI). Participants were screened from amongst consecutive TBI admissions for moderate to severe brain injury, and for pre-injury neurological, psychiatric, or substance abuse histories. Clinical and content scale scores on the MMPI-2 were explored in relation to patient gender, age, level of education, and extent of cognitive complaints. The results revealed diverse psychosocial problem areas across the sample, the most common of which were somatic and cognitive complaints, compromised insight, and a naively optimistic self-perception. The mediating roles of injury severity and demographic variables are discussed. Clinical implications and specific recommendations are presented.

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.

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.

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.

Enteral Nutrition for TBI Patients in the Rehabilitation Setting: Associations with Patient Pre-injury and Injury Characteristics and Outcomes

PubMed Central

Horn, Susan D.; Kinikini, Merin; Moore, Linda W.; Hammond, Flora M.; Brandstater, Murray E.; Smout, Randall J.; Barrett, Ryan S.

2015-01-01

Objective To determine the association of enteral nutrition (EN) with patient pre-injury and injury characteristics and outcomes for patients receiving inpatient brain injury rehabilitation. Design Prospective observational study using propensity scores to isolate the effect of EN Setting 9 rehabilitation centers in the US Participants Patients (n=1701) admitted for first full inpatient rehabilitation after a TBI index injury Interventions Not applicable Main Outcome Measures Functional Independence Measure (FIM) at rehabilitation discharge, length of stay (LOS), weight loss, and presence of infections. Results There were many significant differences in pre-injury and injury characteristics for patients who received EN compared to patients who did not. After matching patients with a propensity score >40% for the likely use of EN, patients with greater than 25% of their rehabilitation stay receiving EN with either standard or high protein formulas (greater than 20% of calories coming from protein) had better FIM Motor and FIM Cognitive scores at rehabilitation discharge and less weight loss than similar patients not receiving EN. Conclusions For patients receiving inpatient rehabilitation following TBI and matched on a propensity to use EN of >40%, clinicians should strongly consider, when possible, EN for at least 25% of the patient’s stay and especially with a formula that contains at least 20% protein rather than a standard formula. PMID:26212401

Acute Gonadotroph and Somatotroph Hormonal Suppression after Traumatic Brain Injury

PubMed Central

Wagner, Justin; Dusick, Joshua R.; McArthur, David L.; Cohan, Pejman; Wang, Christina; Swerdloff, Ronald; Boscardin, W. John

2010-01-01

Abstract Hormonal dysfunction is a known consequence of moderate and severe traumatic brain injury (TBI). In this study we determined the incidence, time course, and clinical correlates of acute post-TBI gonadotroph and somatotroph dysfunction. Patients had daily measurement of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, estradiol, growth hormone, and insulin-like growth factor-1 (IGF-1) for up to 10 days post-injury. Values below the fifth percentile of a healthy cohort were considered abnormal, as were non-measurable growth hormone (GH) values. Outcome measures were frequency and time course of hormonal suppression, injury characteristics, and Glasgow Outcome Scale (GOS) score. The cohort consisted of 101 patients (82% males; mean age 35 years; Glasgow Coma Scale [GCS] score ≤8 in 87%). In men, 100% had at least one low testosterone value, and 93% of all values were low; in premenopausal women, 43% had at least one low estradiol value, and 39% of all values were low. Non-measurable GH levels occurred in 38% of patients, while low IGF-1 levels were observed in 77% of patients, but tended to normalize within 10 days. Multivariate analysis revealed associations of younger age with low FSH and low IGF-1, acute anemia with low IGF-1, and older age and higher body mass index (BMI) with low GH. Hormonal suppression was not predictive of GOS score. These results indicate that within 10 days of complicated mild, moderate, and severe TBI, testosterone suppression occurs in all men and estrogen suppression occurs in over 40% of women. Transient somatotroph suppression occurs in over 75% of patients. Although this acute neuroendocrine dysfunction may not be TBI-specific, low gonadal steroids, IGF-1, and GH may be important given their putative neuroprotective functions. PMID:20214417

Frontal assessment battery (FAB) performance following traumatic brain injury hospitalized in an acute care setting.

PubMed

Rojas, Natalia; Laguë-Beauvais, Maude; Belisle, Arielle; Lamoureux, Julie; AlSideiri, Ghusn; Marcoux, Judith; Maleki, Mohammed; Alturki, Abdulrahman Y; Anchouche, Sonia; Alquraini, Hanan; Feyz, Mitra; Guise, Elaine de

2018-01-19

The Frontal Assessment Battery (FAB) has been shown to be useful in several clinical settings. The aim of the present study was to examine the performance of patients with traumatic brain injury (TBI) on the FAB and to predict their acute outcome. The FAB was administered to 89 patients with mild (27 = uncomplicated and 39 = complicated) and moderate (n = 23) TBI during hospitalization in an acute care setting. The length of stay in days (LOS), Glasgow Outcome Scale-Revised score (GOSE) and Disability Rating Scale (DRS) score were collected. Results showed no significant differences between the three groups on the FAB score, but age and education were significantly associated with the FAB score. Parietal lesions were associated with lower total FAB score, and with the Similarities, Motor series and Conflicting instructions subscales, while frontal lesions were associated with lower performance on the Motor series and Conflicting instructions subscales. Total FAB score was significantly correlated with all outcome measures, and together the FAB total score and the Glasgow Coma Scale (GCS) score explained 30.8% of the variance in the DRS score. The FAB may be useful clinically to acutely assess frontal and parietal lobe functions at bedside in patients with TBI and, in combination with the GCS score to measure TBI severity, can enable clinicians to predict early outcome.

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.

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.

External Validation and Recalibration of Risk Prediction Models for Acute Traumatic Brain Injury among Critically Ill Adult Patients in the United Kingdom.

PubMed

Harrison, David A; Griggs, Kathryn A; Prabhu, Gita; Gomes, Manuel; Lecky, Fiona E; Hutchinson, Peter J A; Menon, David K; Rowan, Kathryn M

2015-10-01

This study validates risk prediction models for acute traumatic brain injury (TBI) in critical care units in the United Kingdom and recalibrates the models to this population. The Risk Adjustment In Neurocritical care (RAIN) Study was a prospective, observational cohort study in 67 adult critical care units. Adult patients admitted to critical care following acute TBI with a last pre-sedation Glasgow Coma Scale score of less than 15 were recruited. The primary outcomes were mortality and unfavorable outcome (death or severe disability, assessed using the Extended Glasgow Outcome Scale) at six months following TBI. Of 3626 critical care unit admissions, 2975 were analyzed. Following imputation of missing outcomes, mortality at six months was 25.7% and unfavorable outcome 57.4%. Ten risk prediction models were validated from Hukkelhoven and colleagues, the Medical Research Council (MRC) Corticosteroid Randomisation After Significant Head Injury (CRASH) Trial Collaborators, and the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) group. The model with the best discrimination was the IMPACT "Lab" model (C index, 0.779 for mortality and 0.713 for unfavorable outcome). This model was well calibrated for mortality at six months but substantially under-predicted the risk of unfavorable outcome. Recalibration of the models resulted in small improvements in discrimination and excellent calibration for all models. The risk prediction models demonstrated sufficient statistical performance to support their use in research and audit but fell below the level required to guide individual patient decision-making. The published models for unfavorable outcome at six months had poor calibration in the UK critical care setting and the models recalibrated to this setting should be used in future research.

Intravenous Busulfan Compared with Total Body Irradiation Pretransplant Conditioning for Adults with Acute Lymphoblastic Leukemia.

PubMed

Kebriaei, Partow; Anasetti, Claudio; Zhang, Mei-Jie; Wang, Hai-Lin; Aldoss, Ibrahim; de Lima, Marcos; Khoury, H Jean; Sandmaier, Brenda M; Horowitz, Mary M; Artz, Andrew; Bejanyan, Nelli; Ciurea, Stefan; Lazarus, Hillard M; Gale, Robert Peter; Litzow, Mark; Bredeson, Christopher; Seftel, Matthew D; Pulsipher, Michael A; Boelens, Jaap-Jan; Alvarnas, Joseph; Champlin, Richard; Forman, Stephen; Pullarkat, Vinod; Weisdorf, Daniel; Marks, David I

2018-04-01

Total body irradiation (TBI) has been included in standard conditioning for acute lymphoblastic leukemia (ALL) before hematopoietic cell transplantation (HCT). Non-TBI regimens have incorporated busulfan (Bu) to decrease toxicity. This retrospective study analyzed TBI and Bu on outcomes of ALL patients 18-60 years old, in first or second complete remission (CR), undergoing HLA-compatible sibling, related, or unrelated donor HCT, who reported to the Center for International Blood and Marrow Transplant Research from 2005 to 2014. TBI plus etoposide (25%) or cyclophosphamide (75%) was used in 819 patients, and intravenous Bu plus fludarabine (41%), clofarabine (30%), cyclophosphamide (15%), or melphalan (13%) was used in 299 patients. Bu-containing regimens were analyzed together, since no significant differences for patient outcomes were noted between them. Bu patients were older, with better performance status; took longer to achieve first CR and receive HCT; were treated more recently; and were more likely to receive peripheral blood grafts, antithymocyte globulin, or tyrosine kinase inhibitors. With median follow-up of 3.6 years for Bu and 5.3 years for TBI, adjusted 3-year outcomes showed treatment-related mortality Bu 19% versus TBI 25% (P = .04); relapse Bu 37% versus TBI 28% (P = .007); disease-free survival (DFS) Bu 45% versus TBI 48% (P = .35); and overall survival (OS) Bu 57% versus TBI 53% (P = .35). In multivariate analysis, Bu patients had higher risk of relapse (relative risk, 1.46; 95% confidence interval, 1.15 to 1.85; P = .002) compared with TBI patients. Despite the higher relapse, Bu-containing conditioning led to similar OS and DFS following HCT for ALL. Copyright © 2018. Published by Elsevier Inc.

Thaliporphine Derivative Improves Acute Lung Injury after Traumatic Brain Injury

PubMed Central

Chen, Gunng-Shinng; Huang, Kuo-Feng; Huang, Chien-Chu; Wang, Jia-Yi

2015-01-01

Acute lung injury (ALI) occurs frequently in patients with severe traumatic brain injury (TBI) and is associated with a poor clinical outcome. Aquaporins (AQPs), particularly AQP1 and AQP4, maintain water balances between the epithelial and microvascular domains of the lung. Since pulmonary edema (PE) usually occurs in the TBI-induced ALI patients, we investigated the effects of a thaliporphine derivative, TM-1, on the expression of AQPs and histological outcomes in the lung following TBI in rats. TM-1 administered (10 mg/kg, intraperitoneal injection) at 3 or 4 h after TBI significantly reduced the elevated mRNA expression and protein levels of AQP1 and AQP4 and diminished the wet/dry weight ratio, which reflects PE, in the lung at 8 and 24 h after TBI. Postinjury TM-1 administration also improved histopathological changes at 8 and 24 h after TBI. PE was accompanied with tissue pathological changes because a positive correlation between the lung injury score and the wet/dry weight ratio in the same animal was observed. Postinjury administration of TM-1 improved ALI and reduced PE at 8 and 24 h following TBI. The pulmonary-protective effect of TM-1 may be attributed to, at least in part, downregulation of AQP1 and AQP4 expression after TBI. PMID:25705683

NIR light propagation in a digital head model for traumatic brain injury (TBI)

PubMed Central

Francis, Robert; Khan, Bilal; Alexandrakis, George; Florence, James; MacFarlane, Duncan

2015-01-01

Near infrared spectroscopy (NIRS) is capable of detecting and monitoring acute changes in cerebral blood volume and oxygenation associated with traumatic brain injury (TBI). Wavelength selection, source-detector separation, optode density, and detector sensitivity are key design parameters that determine the imaging depth, chromophore separability, and, ultimately, clinical usefulness of a NIRS instrument. We present simulation results of NIR light propagation in a digital head model as it relates to the ability to detect intracranial hematomas and monitor the peri-hematomal tissue viability. These results inform NIRS instrument design specific to TBI diagnosis and monitoring. PMID:26417498

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�

Time to cranial computerised tomography for acute traumatic brain injury in paediatric patients: Effect of the shorter stays in emergency departments target in New Zealand.

PubMed

Jones, Peter G; Kool, Bridget; Dalziel, Stuart; Shepherd, Michael; Le Fevre, James; Harper, Alana; Wells, Susan; Stewart, Joanna; Curtis, Elana; Reid, Papaarangi; Ameratunga, Shanthi

2017-07-01

Timely access to computerised tomography (CT) for acute traumatic brain injuries (TBIs) facilitates rapid diagnosis and surgical intervention. In 2009, New Zealand introduced a mandatory target for emergency department (ED) stay such that 95% of patients should leave ED within 6 h of arrival. This study investigated whether this target influenced the timeliness of cranial CT scanning in children who presented to ED with acute TBI. We retrospectively reviewed a random sample of charts of children <15 years with acute TBI from 2006 to 2012. Cases were identified using International Classification of Disease 10 codes consistent with TBI. General linear models investigated changes in time to CT and other indicators before and after the shorter stays in ED target was introduced in 2009. Among the 190 cases eligible for study (n = 91 pre-target and n = 99 post-target), no significant difference was found in time to CT scan pre- and post-target: least squares mean (LSM) with 95% confidence interval = 68 (56-81) versus 65 (53-78) min, respectively, P = 0.66. Time to neurosurgery (LSM 8.7 (5-15) vs. 5.1 (2.6-9.9) h, P = 0.19, or hospital length of stay (LSM: 4.9 (3.9-6.3) vs. 5.2 (4.1-6.7) days, P = 0.69) did not change significantly. However, ED length of stay decreased by 45 min in the post-target period (LSM = 211 (187-238) vs. 166 (98-160) min, P = 0.006). Implementation of the shorter stays in ED target was not associated with a change in the time to CT for children presenting with acute TBI, but an overall reduction in the time spent in ED was apparent. © 2017 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

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.

The Total Body Irradiation Schedule Affects Acute Leukemia Relapse After Matched T Cell–Depleted Hematopoietic Stem Cell Transplantation

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

Aristei, Cynthia, E-mail: cynthia.aristei@unipg.it; Carotti, Alessandra; Palazzari, Elisa

Purpose: We sought to determine whether the total body irradiation (TBI) schedule affected outcome in patients with acute leukemia in complete remission who received T cell–depleted allogeneic hematopoietic stem cell transplantation from HLA identical siblings. Methods and Materials: The study recruited 55 patients (median age, 48 years; age range, 20-66 years; 30 men and 25 women; 34 with acute myeloid leukemia and 21 with acute lymphoid leukemia). Hyperfractionated TBI (HTBI) (1.2 Gy thrice daily for 4 days [for a total dose of 14.4 Gy] from day −12 to day −9) was administered to 29 patients. Single-dose TBI (STBI) (8 Gy, at a median dose rate of 10.7 cGy/minmore » on day −9) was given to 26 patients. Results: All patients achieved primary, sustained engraftment with full donor-type chimerism. At 10 years, the overall cumulative incidence of transplant-related mortality was 11% (SE, ±0.1%). It was 7% (SE, ±0.2%) after HTBI and 15% (SE, ±0.5%) after STBI (P=.3). The overall cumulative incidence of relapse was 33% (SE, ±0.5). It was 13% (SE, ±0.5%) after HTBI and 46% (SE, ±1%) after STBI (P=.02). The overall probability of disease-free survival (DFS) was 59% (SE, ±7%). It was 67% (SE, ±0.84%) after HTBI and 37% (SE, ±1.4%) after STBI (P=.01). Multivariate analyses showed the TBI schedule was the only risk factor that significantly affected relapse and DFS (P=.01 and P=.03, respectively). Conclusions: In patients with acute leukemia, HTBI is more efficacious than STBI in eradicating minimal residual disease after HLA-matched T cell–depleted hematopoietic stem cell transplantation, thus affecting DFS.« less

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 ...

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.

External Validation and Recalibration of Risk Prediction Models for Acute Traumatic Brain Injury among Critically Ill Adult Patients in the United Kingdom

PubMed Central

Griggs, Kathryn A.; Prabhu, Gita; Gomes, Manuel; Lecky, Fiona E.; Hutchinson, Peter J. A.; Menon, David K.; Rowan, Kathryn M.

2015-01-01

Abstract This study validates risk prediction models for acute traumatic brain injury (TBI) in critical care units in the United Kingdom and recalibrates the models to this population. The Risk Adjustment In Neurocritical care (RAIN) Study was a prospective, observational cohort study in 67 adult critical care units. Adult patients admitted to critical care following acute TBI with a last pre-sedation Glasgow Coma Scale score of less than 15 were recruited. The primary outcomes were mortality and unfavorable outcome (death or severe disability, assessed using the Extended Glasgow Outcome Scale) at six months following TBI. Of 3626 critical care unit admissions, 2975 were analyzed. Following imputation of missing outcomes, mortality at six months was 25.7% and unfavorable outcome 57.4%. Ten risk prediction models were validated from Hukkelhoven and colleagues, the Medical Research Council (MRC) Corticosteroid Randomisation After Significant Head Injury (CRASH) Trial Collaborators, and the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) group. The model with the best discrimination was the IMPACT “Lab” model (C index, 0.779 for mortality and 0.713 for unfavorable outcome). This model was well calibrated for mortality at six months but substantially under-predicted the risk of unfavorable outcome. Recalibration of the models resulted in small improvements in discrimination and excellent calibration for all models. The risk prediction models demonstrated sufficient statistical performance to support their use in research and audit but fell below the level required to guide individual patient decision-making. The published models for unfavorable outcome at six months had poor calibration in the UK critical care setting and the models recalibrated to this setting should be used in future research. PMID:25898072

Virtual Environment TBI Screen (VETS)

DTIC Science & Technology

2014-10-01

balance challenges performed on a modified Wii Balance Board . Implementation of this device will enhance current approaches in TBI and mild TBI (i.e...TBI) screen (VETS) device in measuring standing balance . This system consists of software, a Wii balance board , and a large screen television that...Validate Wii ™ Balance Board relative to NeuroCom forceplate ! Running Wii Balance Board validation protocol. ! Milestone Achieved:

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.

Readmission to Acute Care Hospital during Inpatient Rehabilitation for Traumatic Brain Injury

PubMed Central

Hammond, Flora M.; Horn, Susan D.; Smout, Randall J.; Beaulieu, Cynthia L.; Barrett, Ryan S.; Ryser, David K.; Sommerfeld, Teri

2015-01-01

Objective To investigate frequency, reasons, and factors associated with readmission to acute care (RTAC) during inpatient rehabilitation for traumatic brain injury (TBI). Design Prospective observational cohort. Setting Inpatient rehabilitation. Participants 2,130 consecutive admissions for TBI rehabilitation. Interventions Not applicable. Main Outcome Measure(s) RTAC incidence, RTAC causes, rehabilitation length of stay (RLOS), and rehabilitation discharge location. Results 183 participants (9%) experienced RTAC for a total 210 episodes. 161 patients experienced 1 RTAC episode, 17 had 2, and 5 had 3. Mean days from rehabilitation admission to first RTAC was 22 days (SD 22). Mean duration in acute care during RTAC was 7 days (SD 8). 84 participants (46%) had >1 RTAC episode for medical reasons, 102 (56%) had >1 RTAC for surgical reasons, and RTAC reason was unknown for 6 (3%) participants. Most common surgical RTAC reasons were: neurosurgical (65%), pulmonary (9%), infection (5%), and orthopedic (5%); most common medical reasons were infection (26%), neurologic (23%), and cardiac (12%). Older age, history of coronary artery disease, history of congestive heart failure, acute care diagnosis of depression, craniotomy or craniectomy during acute care, and presence of dysphagia at rehabilitation admission predicted patients with RTAC. RTAC was less likely for patients with higher admission Functional Independence Measure Motor scores and education less than high school diploma. RTAC occurrence during rehabilitation was significantly associated with longer RLOS and smaller likelihood of discharge home. Conclusion(s) Approximately 9% of patients with TBI experience RTAC during inpatient rehabilitation for various medical and surgical reasons. This information may help inform interventions aimed at reducing interruptions in rehabilitation due to RTAC. RTACs were associated with longer RLOS and discharge to an institutional setting. PMID:26212405

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.

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

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

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.

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

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

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

An evaluation of the clinical and cost-effectiveness of alternative care locations for critically ill adult patients with acute traumatic brain injury.

PubMed

Grieve, R; Sadique, Z; Gomes, M; Smith, M; Lecky, F E; Hutchinson, P J A; Menon, D K; Rowan, K M; Harrison, D A

2016-08-01

For critically ill adult patients with acute traumatic brain injury (TBI), we assessed the clinical and cost-effectiveness of: (a) Management in dedicated neurocritical care units versus combined neuro/general critical care units within neuroscience centres. (b) 'Early' transfer to a neuroscience centre versus 'no or late' transfer for those who present at a non-neuroscience centre. The Risk Adjustment In Neurocritical care (RAIN) Study included prospective admissions following acute TBI to 67 UK adult critical care units during 2009-11. Data were collected on baseline case-mix, mortality, resource use, and at six months, Glasgow Outcome Scale Extended (GOSE), and quality of life (QOL) (EuroQol 5D-3L). We report incremental effectiveness, costs and cost per Quality-Adjusted Life Year (QALY) of the alternative care locations, adjusting for baseline differences with validated risk prediction models. We tested the robustness of results in sensitivity analyses. Dedicated neurocritical care unit patients (N = 1324) had similar six-month mortality, higher QOL (mean gain 0.048, 95% CI -0.002 to 0.099) and increased average costs compared with those managed in combined neuro/general units (N = 1341), with a lifetime cost per QALY gained of £14,000. 'Early' transfer to a neuroscience centre (N = 584) was associated with lower mortality (odds ratio 0.52, 0.34-0.80), higher QOL for survivors (mean gain 0.13, 0.032-0.225), but positive incremental costs (£15,001, £11,123 to £18,880) compared with 'late or no transfer' (N = 263). The lifetime cost per QALY gained for 'early' transfer was £11,000. For critically ill adult patients with acute TBI, within neuroscience centres management in dedicated neurocritical care units versus combined neuro/general units led to improved QoL and higher costs, on average, but these differences were not statistically significant. This study finds that 'early' transfer to a neuroscience centre is associated with reduced

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.

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.

Role of hormonal levels on hospital mortality for male patients with severe traumatic brain injury.

PubMed

Hohl, Alexandre; Ronsoni, Marcelo Fernando; Debona, Rodrigo; Ben, Juliana; Schwarzbold, Marcelo Liborio; Diaz, Alexandre Paim; Thais, Maria Emília Rodrigues de Oliveira; Linhares, Marcelo Neves; Latini, Alexandra; Prediger, Rui Daniel; Pizzol, Felipe Dal; Walz, Roger

2014-01-01

Changes in hormone blood levels during the acute phase of traumatic brain injury (TBI) have been described in the literature. The objective was to investigate the association among several hormones plasma levels in the acute phase of severe TBI and the hospital mortality rate of male patients. The independent association among plasma levels of TSH, LH, FSH, GH, free T4, cortisol, IGF-1 and total testosterone was measured 10 hours and 30 hours after severe TBI and the hospital mortality of 60 consecutive male patients was evaluated. At least one hormonal level abnormality was demonstrated in 3.6-73.1% of patients. The multiple logistic regressions showed a trend for an independent association among hospital mortality and normal or elevated LH levels measured at 10 hours (OR = 3.7, 95% CI = 0.8-16.3, p = 0.08) and 30 hours (OR = 3.9, 95% CI = 0.9-16.7, p = 0.06). Admission with abnormal pupils and a lower Glasgow Coma Score also were independently associated with hospital mortality. The hormonal changes are frequent in the acute phase of severe TBI. The hormones plasma levels, excepting the LH, are not highly consistent with the hospital mortality of male patients.

Care management of the agitation or aggressiveness crisis in patients with TBI. Systematic review of the literature and practice recommendations.

PubMed

Luauté, Jacques; Plantier, David; Wiart, Laurent; Tell, Laurence

2016-02-01

The agitation crisis in the awakening phase after traumatic brain injury (TBI) is one of the most difficult behavioral disorders to alleviate. Current treatment options are heterogeneous and may involve excessive sedation. Practice guidelines are required by professionals in charge of TBI patients. Few reviews were published but those are old and based on expert opinions. The purpose of this work is to propose evidence-based guidelines to treat the agitation crisis. The elaboration of these guidelines followed the procedure validated by the French health authority for good practice recommendations, close to the Prisma statement. Guidelines were elaborated on the basis of a systematic and critical review of the literature. Twenty-eight articles concerning 376 patients were analyzed. Recommendations are: when faced with an agitation crisis, the management strategy implies to search for an underlying factor that should be treated such as pain, acute sepsis, and drug adverse effect (expert opinion). Physical restraints should be discarded when possible (expert opinion). Neuroleptic agent with a marketing authorization can be used in order to obtain a quick sedation so as to protect the patient from himself, closed ones or the healthcare team but the duration should be as short as possible (expert opinion). The efficacy of beta-blockers and antiepileptics with mood regulation effects like carbamazepine and valproate yield the most compelling evidence and should be preferably used when a background regimen is envisioned (grade B for beta-blocker and C for antiepileptics). Neuroleptics, antidepressants, benzodiazepines, buspirone may be prescribed but are considered second-line treatments (expert opinion). This study provides a strategy for treating the agitation crisis based on scientific data and expert opinion. The level of evidence remains low and published data are often old. New studies are essential to validate results from previous studies and test new drugs and

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

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

Hypothalamic-pituitary dysfunction following traumatic brain injury affects functional improvement during acute inpatient rehabilitation.

PubMed

Rosario, Emily R; Aqeel, Rubina; Brown, Meghan A; Sanchez, Gabriel; Moore, Colleen; Patterson, David

2013-01-01

To evaluate the occurrence of hypothalamic-pituitary dysfunction following a traumatic brain injury (TBI) and to determine its effect on functional improvement in acute inpatient rehabilitation. A retrospective chart review identified male patients with a primary diagnosis of TBI with or without a skull fracture, an onset date within 6 months prior to admission, and were 16 years of age or older. The percentage of individuals in this population with abnormal hormone levels was determined on the basis of the established normal reference range for each hormone assay. The functional independence measure, which assesses functional outcomes in acute inpatient rehabilitation, was used to examine the relationship between hormone levels and functional improvement. Hypothalamic-pituitary dysfunction was identified in nearly 70% of men following TBI. Hypogonadism, or low testosterone levels, was observed in 66% of the patients, followed by low levels of free T4 in 46% and low levels of insulin growth factor-1 in 26% of patients. Hypopituitarism associated with impaired functional recovery. Specifically, the functional independence measure change per day was significantly lower in patients with low levels of testosterone and insulin growth factor-1. These findings suggest the importance of testosterone and insulin growth factor-1 activity in the early stages of physical and cognitive rehabilitation.

Erythropoietin-Derived Peptide Protects Against Acute Lung Injury After Rat Traumatic Brain Injury.

PubMed

Liu, Yuan; Lu, Junyu; Wang, Xiaoya; Chen, Liu; Liu, Su; Zhang, Zhiren; Yao, Wei

2017-01-01

Traumatic brain injury (TBI) can be complicated by TBI-triggered acute lung injury (ALI), in which inflammation plays a central role. It has been reported that an Erythropoietin-derived peptide (pHBSP) was able to ameliorate TBI; however, its function in TBI-caused ALI has not been reported yet. In this study, we studied the effect of pHBSP on TBI-caused ALI by using a weight-drop induced TBI model. At 8 h and 24 h post-TBI, pulmonary edema (PE) and bronchoalveolar lavage fluid (BALF) proteins were measured, and haematoxylin and eosin (H&E) staining of lung sections was carried out. At 24 h following TBI, the lungs were harvested for immunofluorescence staining and qRT-PCR analysis. At 8 h and 24 h post-TBI, pHBSP treatment significantly decreased wet/dry ratios, decreased total BALF protein, and attenuated the histological signs of pulmonary injury. At 24 h post-TBI, pHBSP treatment decreased the accumulation of CD68+ macrophages in the lung and reduced the mRNA levels of TNF-α, IL-6, IL-1β and iNOS in the lung. We identified the protective role that pHBSP played in TBI-caused ALI, suggesting that pHBSP is a potent candidate for systemic therapy in TBI patients. © 2017 The Author(s)Published by S. Karger AG, Basel.

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.

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.

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

Repeat neuroimaging of mild traumatic brain-injured patients with acute traumatic intracranial hemorrhage: clinical outcomes and radiographic features.

PubMed

Kreitzer, Natalie; Lyons, Michael S; Hart, Kim; Lindsell, Cristopher J; Chung, Sora; Yick, Andrew; Bonomo, Jordan

2014-10-01

Emergency department (ED) management of mild traumatic brain injury (TBI) patients with any form of traumatic intracranial hemorrhage (ICH) is variable. Since 2000, our center's standard practice has been to obtain a repeat head computed tomography (CT) at least 6 hours after initial imaging. Patients are eligible for discharge if clinical and CT findings are stable. Whether this practice is safe is unknown. This study characterized clinical outcomes in mild TBI patients with acute traumatic ICH seen on initial ED neuroimaging. This retrospective cohort study included patients presenting to the ED with blunt mild TBI with Glasgow Coma Scale (GCS) scores of 14 or 15 and stable vital signs, during the period from January 2001 to January 2010. Patients with any ICH on initial head CT and repeat head CT within 24 hours were eligible. Cases were excluded for initial GCS < 14, injury > 24 hours old, pregnancy, concomitant nonminor injuries, and coagulopathy. A single investigator abstracted data from records using a standardized case report form and data dictionary. Primary endpoints included death, neurosurgical procedures, and for discharged patients, return to the ED within 7 days. Differences in proportions were computed with 95% confidence intervals (CIs). Of 1,011 patients who presented to the ED and had two head CTs within 24 hours, 323 (32%) met inclusion criteria. The median time between CT scans was 6 hours (interquartile range = 5 to 7 hours). A total of 153 (47%) patients had subarachnoid hemorrhage, 132 (41%) patients had subdural hemorrhage, 11 (3%) patients had epidural hemorrhage, 78 (24%) patients had cerebral contusions, and 59 (18%) patients had intraparenchymal hemorrhage. Four of 323 (1.2%, 95% CI = 0.3% to 3.2%) patients died within 2 weeks of injury. Three of the patients who died had been admitted from the ED on their initial visits, and one had been discharged home. There were 206 patients (64%) discharged from the ED, 28 (13.6%) of whom returned

Late Complications in acute Leukemia patients following HSCT: A single center experience.

PubMed

Vaezi, Mohammad; Gharib, Cyrous; Souri, Maryam; Ghavamzadeh, Ardeshir

2016-01-01

Hematopoietic stem cell transplantation (HSCT) is currently the only curative treatment for acute leukemia. As HSCT improves the long-term survival, it is necessary to assess the late-onset complications affecting the quality of life following HSCT. The study included 122 patients (65 male, 57 female) with leukemia (72 AML and 50 ALL) who received transplants from fully- matched siblings, unrelated donors and unrelated cord blood donors between February 2013 and August 2014 in Shariati Hospital. All study participants were over 18 years of age and had the minimum and maximum survival of 2 and 5 years, respectively. Patients who received HLA-haploidentical SCT were excluded from the study. All allogeneic recipients received busulfan and cyclophosphamide as conditioning regimen. Nobody received TBI-based conditioning regimen in this study. Patients were evaluated for cardiovascular, vision, psychological, endocrine, fertility problems and secondary malignancies one year after transplantation. Results : Data were analyzed using SPSS 15.0. Mitral and tricuspid regurgitation (TR/MR) were the most common cardiac complications (n=12, 10.5%).Thirty-nine percent of patients had psychological problems, especially depression (34%). Cataract was observed in 13% of patients and 34% complained of dry eye. Symptomatic pulmonary changes were found in 13 patients (10.6%). None of the HSCT survivors had experienced fertility before study entry. According to LH and FSH levels, 15% and 9% of females had ovarian failure, respectively. Testosterone level was less than normal in 49(84%) men and, according to their FSH and LH level, 20 (41%) had secondary hypogonadism and 29 (59%) had primary gonadal dysfunction. The results showed that patients who received Bu/Cy conditioning regimen experienced fewer late side effects such as cataract formation and hypothyroidism, compared to previous studies using TBI-based conditioning regimen.

Late Complications in acute Leukemia patients following HSCT: A single center experience

PubMed Central

Vaezi, Mohammad; Gharib, Cyrous; Souri, Maryam; Ghavamzadeh, Ardeshir

2016-01-01

Background: Hematopoietic stem cell transplantation (HSCT) is currently the only curative treatment for acute leukemia. As HSCT improves the long-term survival, it is necessary to assess the late-onset complications affecting the quality of life following HSCT. Subjects and Methods: The study included 122 patients (65 male, 57 female) with leukemia (72 AML and 50 ALL) who received transplants from fully- matched siblings, unrelated donors and unrelated cord blood donors between February 2013 and August 2014 in Shariati Hospital. All study participants were over 18 years of age and had the minimum and maximum survival of 2 and 5 years, respectively. Patients who received HLA-haploidentical SCT were excluded from the study. All allogeneic recipients received busulfan and cyclophosphamide as conditioning regimen. Nobody received TBI-based conditioning regimen in this study. Patients were evaluated for cardiovascular, vision, psychological, endocrine, fertility problems and secondary malignancies one year after transplantation. Results : Data were analyzed using SPSS 15.0. Mitral and tricuspid regurgitation (TR/MR) were the most common cardiac complications (n=12, 10.5%).Thirty-nine percent of patients had psychological problems, especially depression (34%). Cataract was observed in 13% of patients and 34% complained of dry eye. Symptomatic pulmonary changes were found in 13 patients (10.6%). None of the HSCT survivors had experienced fertility before study entry. According to LH and FSH levels, 15% and 9% of females had ovarian failure, respectively. Testosterone level was less than normal in 49(84%) men and, according to their FSH and LH level, 20 (41%) had secondary hypogonadism and 29 (59%) had primary gonadal dysfunction. Conclusion: The results showed that patients who received Bu/Cy conditioning regimen experienced fewer late side effects such as cataract formation and hypothyroidism, compared to previous studies using TBI-based conditioning regimen. PMID

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

Readmission to an Acute Care Hospital During Inpatient Rehabilitation for Traumatic Brain Injury.

PubMed

Hammond, Flora M; Horn, Susan D; Smout, Randall J; Beaulieu, Cynthia L; Barrett, Ryan S; Ryser, David K; Sommerfeld, Teri

2015-08-01

To assess the incidence of, causes for, and factors associated with readmission to an acute care hospital (RTAC) during inpatient rehabilitation for traumatic brain injury (TBI). Prospective observational cohort. Inpatient rehabilitation. Individuals with TBI admitted consecutively for inpatient rehabilitation (N=2130). Not applicable. RTAC incidence, RTAC causes, rehabilitation length of stay (RLOS), and rehabilitation discharge location. A total of 183 participants (9%) experienced RTAC for a total of 210 episodes. Of 183 participants, 161 patients experienced 1 RTAC episode, 17 had 2, and 5 had 3. The mean time from rehabilitation admission to first RTAC was 22±22 days. The mean duration in acute care during RTAC was 7±8 days. Eighty-four participants (46%) had ≥1 RTAC episodes for medical reasons, 102 (56%) had ≥1 RTAC episodes for surgical reasons, and 6 (3%) participants had RTAC episodes for unknown reasons. Most common surgical RTAC reasons were neurosurgical (65%), pulmonary (9%), infection (5%), and orthopedic (5%); most common medical reasons were infection (26%), neurological (23%), and cardiac (12%). Any RTAC was predicted as more likely for patients with older age, history of coronary artery disease, history of congestive heart failure, acute care diagnosis of depression, craniotomy or craniectomy during acute care, and presence of dysphagia at rehabilitation admission. RTAC was less likely for patients with higher admission FIM motor scores and education less than high school diploma. RTAC occurrence during rehabilitation was significantly associated with longer RLOS and smaller likelihood of discharge home. Approximately 9% of patients with TBI experienced RTAC episodes during inpatient rehabilitation for various medical and surgical reasons. This information may help inform interventions aimed at reducing interruptions in rehabilitation for RTAC. RTACs were associated with longer RLOS and discharge to an institutional setting. Copyright �

Acute clinical care and care coordination for traumatic brain injury within Department of Defense.

PubMed

Jaffee, Michael S; Helmick, Kathy M; Girard, Philip D; Meyer, Kim S; Dinegar, Kathy; George, Karyn

2009-01-01

The nature of current combat situations that U.S. military forces encounter and the use of unconventional weaponry have dramatically increased service personnel's risks of sustaining a traumatic brain injury (TBI). Although the true incidence and prevalence of combat-related TBI are unknown, service personnel returning from deployment have reported rates of concussion between 10% and 20%. The Department of Defense has recently released statistics on TBI dating back to before the wars in Iraq and Afghanistan to better elucidate the impact and burden of TBI on America's warriors and veterans. Patients with severe TBI move through a well-established trauma system of care, beginning with triage of initial injury by first-responders in the war zone to acute care to rehabilitation and then returning home and to the community. Mild and moderate TBIs may pose different clinical challenges, especially when initially undetected or if treatment is delayed because more serious injuries are present. To ensure identification and prompt treatment of mild and moderate TBI, the U.S. Congress has mandated that military and Department of Veterans Affairs hospitals screen all service personnel returning from combat. Military health professionals must evaluate them for concussion and then treat the physical, emotional, and cognitive problems that may surface. A new approach to health management and care coordination is needed that will allow medical transitions between networks of care to become more centralized and allow for optimal recovery at all severity levels. This article summarizes the care systems available for the acute management of TBI from point of injury to stateside military treatment facilities. We describe TBI assessment, treatment, and overall coordination of care, including innovative clinical initiatives now used.

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.

Towards systemic sustainable performance of TBI care systems: emergency leadership frontiers.

PubMed

Caro, Denis H J

2010-11-10

Traumatic brain injuries (TBIs) continue as a twenty-first century subterranean and almost invisible scourge internationally. TBI care systems provide a safety net for survival, recovery, and reintegration into social communities from this scourge, particularly in Canada, the European Union, and the USA. This paper examines the underlying issues of systemic performance and sustainability of TBI care systems, in the light of decreasing care resources and increasing demands for services. This paper reviews the extant literature on TBI care systems, systems reengineering, and emergency leadership literature. This paper presents a seven care layer paradigm, which forms the essence of systemic performance in the care of patients with TBIs. It also identifies five key strategic drivers that hold promise for the future systemic sustainability of TBI care systems. Transformational leadership and engagement from the international emergency medical community is the key to generating positive change. The sustainability/performance care framework is relevant and pertinent for consideration internationally and in the context of other emergency medical populations.

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.

Effect of methylphenidate on ICU and hospital length of stay in patients with severe and moderate traumatic brain injury.

PubMed

Moein, Houshang; Khalili, Hossein A; Keramatian, Kamyar

2006-09-01

Traumatic brain injury is one of the major causes of death and disability among young people. Methylphenidate, a neural stimulant and protective drug, which has been mainly used for childhood attention deficit/hyperactivity disorder, has shown some benefits in late psychosocial problems in patients with traumatic brain injury. Its effect on arousal and consciousness has been also revealed in the sub-acute phase of traumatic brain injury. We studied its effect on the acute phase of moderate and severe traumatic brain injury (TBI) in relation to the length of ICU and hospital admission. Severely and moderately TBI patients (according to inclusion and exclusion criteria) were randomized to treatment and control groups. The treatment group received methylphenidate 0.3mg/kg per dose PO BID by the second day of admission until the time of discharge, and the control group received a placebo. Admission information and daily Glasgow Coma Scale (GCS) were recorded. Medical, surgical, and discharge plans for patients were determined by the attending physician, blinded to the study. Forty patients with severe TBI (GCS = 5-8) and 40 moderately TBI patients (GCS = 9-12) were randomly divided into treatment and control groups on the day of admission. In the severely TBI patients, both hospital and ICU length of stay, on average, were shorter in the treatment group compared with the control group. In the moderately TBI patients while ICU stay was shorter in the treatment group, there was no significant reduction of the period of hospitalization. There were no significant differences between the treatment and control groups in terms of age, sex, post resuscitation GCS, or brain CT scan findings, in either severely or moderately TBI patients. Methylphenidate was associated with reductions in ICU and hospital length of stay by 23% in severely TBI patients (P = 0.06 for ICU and P = 0.029 for hospital stay time). However, in the moderately TBI patients who received methylphenidate

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

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.

High-dose total-body irradiation and autologous marrow reconstitution in dogs: dose-rate-related acute toxicity and fractionation-dependent long-term survival

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

Deeg, H.J.; Storb, R.; Weiden, P.L.

1981-11-01

Beagle dogs treated by total-body irradiation (TBI) were given autologous marrow grafts in order to avoid death from marrow toxicity. Acute and delayed non-marrow toxicities of high single-dose (27 dogs) and fractionated TBI (20 dogs) delivered at 0.05 or 0.1 Gy/min were compared. Fractionated TBI was given in increments of 2 Gy every 6 hr for three increments per day. Acute toxicity and early mortality (<1 month) at identical total irradiation doses were comparable for dogs given fractionated or single-dose TBI. With single-dose TBI, 14, 16, and 18 Gy, respectively, given at 0.05 Gy/min, 0/5, 5/5, and 2/2 dogs diedmore » from acute toxicity; with 10, 12, and 14 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 5/5 dogs died acutely. With fractionated TBI, 14 and 16 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 2/2 dogs died auctely. Early deaths were due to radiation enteritis with or without associated septicemia (29 dogs; less than or equal to Day 10). Three dogs given 10 Gy of TBI at 0.1 Gy/min died from bacterial pneumonia; one (Day 18) had been given fractionated and two (Days 14, 22) single-dose TBI. Fifteen dogs survived beyond 1 month; eight of these had single-dose TBI (10-14 Gy) and all died within 7 months of irradiation from a syndrome consisting of hepatic damage, pancreatic fibrosis, malnutrition, wasting, and anemia. Seven of the 15 had fractionated TBI, and only one (14 Gy) died on Day 33 from hepatic failure, whereas 6 (10-14 Gy) are alive and well 250 to 500 days after irradiation. In conclusion, fractionated TBI did not offer advantages over single-dose TBI with regard to acute toxicity and early mortality; rather, these were dependent upon the total dose of TBI. The total acutely tolerated dose was dependent upon the exposure rate; however, only dogs given fractionated TBI became healthy long-term survivors.« less

Does an early onset and continuous chain of rehabilitation improve the long-term functional outcome of patients with severe traumatic brain injury?

PubMed

Andelic, Nada; Bautz-Holter, Erik; Ronning, Pal; Olafsen, Kjell; Sigurdardottir, Solrun; Schanke, Anne-Kristine; Sveen, Unni; Tornas, Sveinung; Sandhaug, Maria; Roe, Cecilie

2012-01-01

There are currently no international guidelines regarding treatment in the early rehabilitation phase for persons with severe traumatic brain injury (TBI), and only a few studies have investigated the effect of integrating rehabilitation into acute TBI care. The aim of the study was to evaluate whether a continuous chain of rehabilitation that begins with the acute phase could improve the functional outcome of severe TBI patients, compared to a broken chain of rehabilitation that starts in the sub-acute phase of TBI. A total of 61 surviving patients with severe TBI were included in a quasi-experimental study conducted at the Level I trauma center in Eastern Norway. In the study, 31 patients were in the early rehabilitation group (Group A) and 30 patients were in the delayed rehabilitation group (Group B). The functional outcomes were assessed 12 months post-injury with the Glasgow Outcome Scale Extended (GOSE) and the Disability Rating Scale (DRS). A favorable outcome (GOSE 6-8) occurred in 71% of the patients from Group A versus 37% in Group B (p=0.007). The DRS score was significantly better in Group A (p=0.03). The ordinal logistic regression analysis was used to quantify the relationship between the type of rehabilitation chain and the GOSE. A better GOSE outcome was found in patients from Group A (unadjusted OR 3.25 and adjusted OR 2.78, respectively). These results support the hypothesis that better functional outcome occurs in patients who receive early onset and a continuous chain of rehabilitation.

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.

Parallel recovery of consciousness and sleep in acute traumatic brain injury.

PubMed

Duclos, Catherine; Dumont, Marie; Arbour, Caroline; Paquet, Jean; Blais, Hélène; Menon, David K; De Beaumont, Louis; Bernard, Francis; Gosselin, Nadia

2017-01-17

To investigate whether the progressive recuperation of consciousness was associated with the reconsolidation of sleep and wake states in hospitalized patients with acute traumatic brain injury (TBI). This study comprised 30 hospitalized patients (age 29.1 ± 13.5 years) in the acute phase of moderate or severe TBI. Testing started 21.0 ± 13.7 days postinjury. Consciousness level and cognitive functioning were assessed daily with the Rancho Los Amigos scale of cognitive functioning (RLA). Sleep and wake cycle characteristics were estimated with continuous wrist actigraphy. Mixed model analyses were performed on 233 days with the RLA (fixed effect) and sleep-wake variables (random effects). Linear contrast analyses were performed in order to verify if consolidation of the sleep and wake states improved linearly with increasing RLA score. Associations were found between scores on the consciousness/cognitive functioning scale and measures of sleep-wake cycle consolidation (p < 0.001), nighttime sleep duration (p = 0.018), and nighttime fragmentation index (p < 0.001). These associations showed strong linear relationships (p < 0.01 for all), revealing that consciousness and cognition improved in parallel with sleep-wake quality. Consolidated 24-hour sleep-wake cycle occurred when patients were able to give context-appropriate, goal-directed responses. Our results showed that when the brain has not sufficiently recovered a certain level of consciousness, it is also unable to generate a 24-hour sleep-wake cycle and consolidated nighttime sleep. This study contributes to elucidating the pathophysiology of severe sleep-wake cycle alterations in the acute phase of moderate to severe TBI. © 2016 American Academy of Neurology.

Characterizing the type and location of intracranial abnormalities in mild traumatic brain injury.

PubMed

Isokuortti, Harri; Iverson, Grant L; Silverberg, Noah D; Kataja, Anneli; Brander, Antti; Öhman, Juha; Luoto, Teemu M

2018-01-12

OBJECTIVE The incidence of intracranial abnormalities after mild traumatic brain injury (TBI) varies widely across studies. This study describes the characteristics of intracranial abnormalities (acute/preexisting) in a large representative sample of head-injured patients who underwent CT imaging in an emergency department. METHODS CT scans were systematically analyzed/coded in the TBI Common Data Elements framework. Logistic regression modeling was used to quantify risk factors for traumatic intracranial abnormalities in patients with mild TBIs. This cohort included all patients who were treated at the emergency department of the Tampere University Hospital (between 2010 and 2012) and who had undergone head CT imaging after suffering a suspected TBI (n = 3023), including 2766 with mild TBI and a reference group with moderate to severe TBI. RESULTS The most common traumatic lesions seen on CT scans obtained in patients with mild TBIs and those with moderate to severe TBIs were subdural hematomas, subarachnoid hemorrhages, and contusions. Every sixth patient (16.1%) with mild TBI had an intracranial lesion compared with 5 of 6 patients (85.6%) in the group with moderate to severe TBI. The distribution of different types of acute traumatic lesions was similar among mild and moderate/severe TBI groups. Preexisting brain lesions were a more common CT finding among patients with mild TBIs than those with moderate to severe TBIs. Having a past traumatic lesion was associated with increased risk for an acute traumatic lesion but neurodegenerative and ischemic lesions were not. A lower Glasgow Coma Scale score, male sex, older age, falls, and chronic alcohol abuse were associated with higher risk of acute intracranial lesion in patients with mild TBI. CONCLUSIONS These findings underscore the heterogeneity of neuropathology associated with the mild TBI classification. Preexisting brain lesions are common in patients with mild TBI, and the incidence of preexisting lesions

Towards systemic sustainable performance of TBI care systems: emergency leadership frontiers

PubMed Central

2010-01-01

Background Traumatic brain injuries (TBIs) continue as a twenty-first century subterranean and almost invisible scourge internationally. TBI care systems provide a safety net for survival, recovery, and reintegration into social communities from this scourge, particularly in Canada, the European Union, and the USA. Aims This paper examines the underlying issues of systemic performance and sustainability of TBI care systems, in the light of decreasing care resources and increasing demands for services. Methods This paper reviews the extant literature on TBI care systems, systems reengineering, and emergency leadership literature. Results This paper presents a seven care layer paradigm, which forms the essence of systemic performance in the care of patients with TBIs. It also identifies five key strategic drivers that hold promise for the future systemic sustainability of TBI care systems. Conclusions Transformational leadership and engagement from the international emergency medical community is the key to generating positive change. The sustainability/performance care framework is relevant and pertinent for consideration internationally and in the context of other emergency medical populations. PMID:21373305

Overview of traumatic brain injury patients at a tertiary trauma centre.

PubMed

de Guise, Elaine; Feyz, Mitra; LeBlanc, Joanne; Richard, Sylvain-Luc; Lamoureux, Julie

2005-05-01

The goal of this study was to provide a general descriptive and cognitive portrait of a population with traumatic brain injury (TBI) at the time of their acute care stay. Three hundred and forty-eight TBI patients were assessed. The following data were collected for each patient: age, level of education, duration of post-traumatic amnesia, Galveston Orientation Amnesia Test score, Glasgow Coma Scale score, results of cerebral imaging, Neurobehavioral Rating Scale score, the Functional Independence Measure cognitive score and the Glasgow Outcome Scale score. The clinical profile of the population revealed a mean age of 40.2 (+/-18.7) and a mean of 11.5 (+/-3.6) years of education. Most patients presented with frontal (57.6%) and temporal (40%) lesions. Sixty-two percent had post-traumatic amnesia of less than 24 hours. Seventy percent presented with mild TBI, 14% with moderate and 15% with severe TBI. The cognitive deficits most frequently observed on the Neurobehavioral Rating Scale were in the areas of attention, memory and mental flexibility as well as slowness and mental fatigability. Most patients had good cognitive outcome on the Functional Independence Measure and scores of 2 and 3 were frequent on the GOS. Forty-five percent of the patients returned home after discharge, 51.7% were referred to in or out patient rehabilitation and 3.2% were transferred to long-term care facilities. Because of the specialized mandate of acute care institutions, the information provided here concerning characteristics of our TBI population is essential for more efficient decision-making and planning/programming with regards to care and service delivery.

Incidence rate of mild traumatic brain injury among patients who have suffered from an isolated limb fracture: Upper limb fracture patients are more at risk.

PubMed

Jodoin, Marianne; Rouleau, Dominique M; Charlebois-Plante, Camille; Benoit, Benoit; Leduc, Stéphane; Laflamme, G-Yves; Gosselin, Nadia; Larson-Dupuis, Camille; De Beaumont, Louis

2016-08-01

This study compares the incidence rate of mild traumatic brain injury (mild TBI) detected at follow-up visits (retrospective diagnosis) in patients suffering from an isolated limb trauma, with the incidence rate held by the hospital records (prospective diagnosis) of the sampled cohort. This study also seeks to determine which types of fractures present with the highest incidence of mild TBI. Retrospective assessment of mild TBI among orthopaedic monotrauma patients, randomly selected for participation in an Orthopaedic clinic of a Level I Trauma Hospital. Patients in the remission phase of a limb fracture were recruited between August 2014 and May 2015. No intervention was done (observational study). Standardized semi-structured interviews were conducted with all patients to retrospectively assess for mild TBI at the time of the fracture. Emergency room related medical records of all patients were carefully analyzed to determine whether a prospective mild TBI diagnosis was made following the accident. A total of 251 patients were recruited (54% females, Mean age=49). Study interview revealed a 23.5% incidence rate of mild TBI compared to an incidence rate of 8.8% for prospective diagnosis (χ(2)=78.47; p<0.0001). Patients suffering from an upper limb monotrauma (29.6%; n=42/142) are significantly more at risk of sustaining a mild TBI compared to lower limb fractures (15.6%; n=17/109) (χ(2)=6.70; p=0.010). More specifically, patients with a proximal upper limb injury were significantly more at risk of sustaining concomitant mild TBI (40.6%; 26/64) compared to distal upper limb fractures (20.25%; 16/79) (χ(2)=7.07; p=0.008). Results suggest an important concomitance of mild TBI among orthopaedic trauma patients, the majority of which go undetected during acute care. Patients treated for an upper limb fracture are particularly at risk of sustaining concomitant mild TBI. Copyright © 2016 Elsevier Ltd. All rights reserved.

Early care of acute hyperglycemia benefits the outcome of traumatic brain injury in rats.

PubMed

Kang, Xin; Liu, Yuepeng; Yuan, Tao; Jiang, Na-Na; Dong, Yan-Bin; Wang, Jian-Wei; Fu, Guang-Hui; Liu, Yu-Liang; Wang, Wen-Xue

2016-11-01

Previous animal studies showed contradictory clinical observations on whether acute hyperglycemia contributes to poor outcome in traumatic brain injury (TBI). Herein, we tried to clarify this issue. Striking with depths of 3.0-4.25mm at right occipitoparietal brain region and with depth of 3.75mm at right/left occipitoparietal or right/left frontoparietal brain region were performed, respectively. Blood glucose and insulin levels were traced every four hours from 1 to 72h after striking. HOMA2-%S and HOMA2-%β were calculated. Modified neurological severity scores (mNSS) were used to evaluate neurological deficit within 72h. Striking with depths of 3.5-4.25mm induced increase in blood glucose lasting up to 24h after striking. The levels of blood glucose after striking with depths of 3.75-4.25mm were significantly different from that of striking with the depth of 3.0mm. Striking with depth of 3.75mm at right/left occipitoparietal region induced higher blood glucose in 24h than that at right/left frontoparietal region. Insulin concentration increased slowly during 72h after striking. Striking also induced decrease in insulin sensitivity and secretion lasting 72h. Evaluation of mNSS revealed that severe striking (beyond 3.75mm) worsened nerve function than slight striking (<3.0mm). Intervention of acute hyperglycemia could decrease the mNSS from 2 to 7 days after TBI. Our results suggested that only severe TBI could induce acute hyperglycemia by itself, and early care of acute hyperglycemia could benefit the outcome of TBI patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Traumatic Brain Injury Practice-Based Evidence Study: Design and Patients, Centers, Treatments, and Outcomes

PubMed Central

Horn, Susan D.; Corrigan, John D.; Bogner, Jennifer; Hammond, Flora M.; Seel, Ronald T.; Smout, Randall J.; Barrett, Ryan S.; Dijkers, Marcel P.; Whiteneck, Gale G.

2015-01-01

Objective To describe study design, patients, centers, treatments, and outcomes of a traumatic brain injury (TBI) practice-based evidence (PBE) study and to evaluate the generalizability of the findings to the US TBI inpatient rehabilitation population. Design Prospective, longitudinal observational study Setting 10 inpatient rehabilitation centers (9 US, 1 Canada) Participants Patients (n=2130) enrolled between October 2008 and Sept 2011, and admitted for inpatient rehabilitation after an index TBI injury Interventions Not applicable Main Outcome Measures Return to acute care during rehabilitation, rehabilitation length of stay, Functional Independence Measure (FIM) at discharge, residence at discharge, and 9 months post-discharge rehospitalization, FIM, participation, and subjective wellbeing. Results Level of admission FIM Cognitive score was found to create relatively homogeneous subgroups for subsequent analysis of best treatment combinations. There were significant differences in patient and injury characteristics, treatments, rehabilitation course, and outcomes by admission FIM Cognitive subgroups. TBI-PBE study patients overall were similar to US national TBI inpatient rehabilitation populations. Conclusions This TBI-PBE study succeeded in capturing naturally occurring variation within patients and treatments, offering opportunities to study best treatments for specific patient deficits. Subsequent papers in this issue report differences between patients and treatments and associations with outcomes in greater detail. PMID:26212396

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

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

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.

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.

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.

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.

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 ...

TBI Patient, Injury, Therapy, and Ancillary Treatments Associated with Outcomes at Discharge and 9 Months Post-discharge

PubMed Central

Horn, Susan D.; Corrigan, John D.; Beaulieu, Cynthia L.; Bogner, Jennifer; Barrett, Ryan S.; Giuffrida, Clare G.; Ryser, David K.; Cooper, Kelli; Carroll, Deborah M.; Deutscher, Daniel

2015-01-01

Objective To examine associations of patient and injury characteristics, inpatient rehabilitation therapy activities, and neurotropic medications with outcomes at discharge and 9 months post-discharge for patients with traumatic brain injury (TBI) Design Prospective, longitudinal observational study Setting 10 inpatient rehabilitation centers (9 US, 1 Canada) Participants Consecutive patients (n=2130) enrolled between 2008 and 2011, admitted for inpatient rehabilitation after an index TBI injury Interventions Not applicable Main Outcome Measures Rehabilitation length of stay, discharge to home, and Functional Independence Measure (FIM) at discharge and 9 months post-discharge Results The admission FIM Cognitive score was used to create 5 relatively homogeneous subgroups for subsequent analysis of treatment outcomes. Within each subgroup, significant associations were found between outcomes and patient and injury characteristics, time spent in therapy activities, and medications used. Patient and injury characteristics explained on average 35.7% of the variation in discharge outcomes and 22.3% in 9-month outcomes. Adding time spent and level of effort in therapy activities, as well as percent of stay using specific medications, explained approximately 20.0% more variation for discharge outcomes and 12.9% for 9-month outcomes. After patient, injury, and treatment characteristics were used to predict outcomes, center differences added only approximately 1.9% additional variance explained. Conclusions At discharge, greater effort during therapy sessions, time spent in more complex therapy activities, and use of specific medications were associated with better outcomes for patients in all admission FIM Cognitive subgroups. At 9 months post-discharge, similar but less pervasive associations were observed for therapy activities, but not classes of medications. Further research is warranted to examine more specific combinations of therapy activities and medications that

Advanced MRI in Acute Military TBI

DTIC Science & Technology

2014-09-01

symptoms onmental health and service discharge outcomes. J Neurotrauma. 2013; 30(16):1391-1397. 16. GalarneauMR,Woodruff SI, Dye JL, Mohrle CR, Wade...related mild traumatic brain injury acute symptoms on mental health and service discharge outcomes. J. Neurotrauma 30, 1391–1397. 22. Casscells, S. (2007...radiation (include optic radiation) left 37 Anterior corona radiata right 102 Anterior corona radiata left 38 Superior corona radiata right 103 Superior

Computed tomography and clinical outcome in patients with severe traumatic brain injury.

PubMed

Stenberg, Maud; Koskinen, Lars-Owe D; Jonasson, Per; Levi, Richard; Stålnacke, Britt-Marie

2017-01-01

To study: (i) acute computed tomography (CT) characteristics and clinical outcome; (ii) clinical course and (iii) Corticosteroid Randomisation after Significant Head Injury acute calculator protocol (CRASH) model and clinical outcome in patients with severe traumatic brain injury (sTBI). Initial CT (CT i ) and CT 24 hours post-trauma (CT 24 ) were evaluated according to Marshall and Rotterdam classifications. Rancho Los Amigos Cognitive Scale-Revised (RLAS-R) and Glasgow Outcome Scale Extended (GOSE) were assessed at three months and one year post-trauma. The prognostic value of the CRASH model was evaluated. Thirty-seven patients were included. Marshall CT i and CT 24 were significantly correlated with RLAS-R at three months. Rotterdam CT 24 was significantly correlated with GOSE at three months. RLAS-R and the GOSE improved significantly from three months to one year. CRASH predicted unfavourable outcome at six months for 81% of patients with bad outcome and for 85% of patients with favourable outcome according to GOSE at one year. Neither CT nor CRASH yielded clinically useful predictions of outcome at one year post-injury. The study showed encouragingly many instances of significant recovery in this population of sTBI. The combination of lack of reliable prognostic indicators and favourable outcomes supports the case for intensive acute management and rehabilitation as the default protocol in the cases of sTBI.

Successful pregnancy following very high-dose total body irradiation (1575 cGy) and bone marrow transplantation in a woman with acute myeloid leukemia.

PubMed

Wang, W S; Tzeng, C H; Hsieh, R K; Chiou, T J; Liu, J H; Yen, C C; Chen, P M

1998-02-01

A 22-year-old woman had a normal full-term delivery 6 years after a successful allogeneic bone marrow transplantation (BMT) for acute myeloid leukemia (AML). Conditioning therapy consisted of cyclophosphamide (120 mg/kg) and total body irradiation (TBI) to a total of 1575 cGy in seven fractions (225 cGy x 7, at a dose rate of 3.5 cGy/min). Graft-versus-host disease prophylaxis was with methotrexate and cyclosporin A. Grade I acute GVHD developed after BMT but there was no chronic GVHD. She became amenorrhoeic after BMT and serial gonadal testing indicated hypergonadotrophic hypogonadism. She became pregnant and delivered a full-term, healthy baby 6 years after BMT. Successful pregnancy after TBI of more than 1200 cGy is extremely rare. This case, to the best of our knowledge, is the second patient who received a higher dose of TBI (1575 cGy) to have a successful pregnancy. This and previous reports indicate that normal pregnancy is possible after BMT with TBI in excess of 1200 cGy.

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

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

Neuroprotection of hyperbaric oxygen therapy in sub-acute traumatic brain injury: not by immediately improving cerebral oxygen saturation and oxygen partial pressure.

PubMed

Zhou, Bao-Chun; Liu, Li-Jun; Liu, Bing

2016-09-01

Although hyperbaric oxygen (HBO) therapy can promote the recovery of neural function in patients who have suffered traumatic brain injury (TBI), the underlying mechanism is unclear. We hypothesized that hyperbaric oxygen treatment plays a neuroprotective role in TBI by increasing regional transcranial oxygen saturation (rSO 2 ) and oxygen partial pressure (PaO 2 ). To test this idea, we compared two groups: a control group with 20 healthy people and a treatment group with 40 TBI patients. The 40 patients were given 100% oxygen of HBO for 90 minutes. Changes in rSO 2 were measured. The controls were also examined for rSO 2 and PaO 2 , but received no treatment. rSO 2 levels in the patients did not differ significantly after treatment, but levels before and after treatment were significantly lower than those in the control group. PaO 2 levels were significantly decreased after the 30-minute HBO treatment. Our findings suggest that there is a disorder of oxygen metabolism in patients with sub-acute TBI. HBO does not immediately affect cerebral oxygen metabolism, and the underlying mechanism still needs to be studied in depth.

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.

Improving identification of traumatic brain injury after nonmilitary bomb blasts.

PubMed

Rutland-Brown, Wesley; Langlois, Jean A; Bazarian, Jeffrey J; Warden, Deborah

2008-01-01

To improve identification of traumatic brain injury (TBI) in survivors of nonmilitary bomb blasts during the acute care phase. The Centers for Disease Control and Prevention convened a meeting of experts in TBI, emergency medicine, and disaster response to review the recent literature and make recommendations. Seven key recommendations were proposed: (1) increase TBI awareness among medical professionals; (2) encourage use of standard definitions and consistent terminology; (3) improve screening methods for TBI in the acute care setting; (4) clarify the distinction between TBI and acute stress disorder; (5) encourage routine screening of hospitalized trauma patients for TBI; (6) improve identification of nonhospitalized TBI patients; and (7) integrate the appropriate level of TBI identification into all-hazards mass casualty preparedness. By adopting these recommendations, the United States could be better prepared to identify and respond to TBI following future bombing events.

Thiotepa-based versus total body irradiation-based myeloablative conditioning prior to allogeneic stem cell transplantation for acute myeloid leukaemia in first complete remission: a retrospective analysis from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation.

PubMed

Eder, Sandra; Labopin, Myriam; Arcese, William; Or, Reuven; Majolino, Ignazio; Bacigalupo, Andrea; de Rosa, Gennaro; Volin, Liisa; Beelen, Dietrich; Veelken, Hendrik; Schaap, Nicolaas P M; Kuball, Jurgen; Cornelissen, Jan; Nagler, Arnon; Mohty, Mohamad

2016-01-01

Thiotepa is an alkylating compound with an antineoplastic and myeloablative activity and can mimic the effect of radiation. However, it is unknown whether this new regimen could safely replace the long-established ones. This retrospective matched-pair analysis evaluated the outcome of adults with acute myeloid leukaemia in first complete remission who received myeloablative conditioning either with a thiotepa-based (n = 121) or a cyclophosphamide/total body irradiation-based (TBI; n = 358) regimen for allogeneic hematopoietic stem cell transplantation from an HLA-matched sibling or an unrelated donor. With a median follow-up of 44 months, the outcome was similar in both groups. Acute graft-versus-host disease grade II-IV was observed in 25% after thiotepa-containing regimen versus 35% after TBI (P = 0.06). The 2-yr cumulative incidence of chronic graft-versus-host disease was 40.5% for thiotepa and 41% for TBI (P = 0.98). At 2 yrs, the cumulative incidences of non-relapse mortality and relapse incidence were 23.9% (thiotepa) vs. 22.4% (TBI; P = 0.66) and 17.2% (thiotepa) vs. 23.3% (TBI; P = 0.77), respectively. The probabilities of leukaemia-free and overall survival at 2 yrs were not significantly different between the thiotepa and TBI groups, at 58.9% vs. 54.2% (P = 0.95) and 61.4% vs. 58% (P = 0.72), respectively. Myeloablative regimens using combinations including thiotepa can provide satisfactory outcomes, but the optimal conditioning remains unclear for the individual patient in this setting. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Treatment of TBI with Hormonal and Pharmacological Support, Preclinical Validation Using Diffuse and Mechanical TBI Animal Models

DTIC Science & Technology

2016-05-01

Award Number: PT075653 (grant) W81XWH-08-2-0153 (contract) TITLE: Treatment of TBI with Hormonal and Pharmacological Support, Preclinical...TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-08-2-0153 Treatment of TBI with Hormonal and Pharmacological Support, Preclinical Validation Using...rats. Our in vivo tests also included MRI imaging, focusing on edema resolution and reduction of diffuse axonal damage (fractional anisotropy

[Allogeneic hematopoietic stem cell transplantation using myeloablative conditioning including total body irradiation for pediatric acute lymphoblastic leukemia: a single-center retrospective analysis].

PubMed

Honda, Mamoru; Arakawa, Yuki; Kawakami, Ryota; Itabashi, Toshikazu; Yanagi, Masato; Sasaki, Koji; Watanabe, Kentaro; Isobe, Kiyotaka; Mori, Makiko; Hanada, Ryoji; Koh, Katsuyoshi

2018-01-01

This study aimed to investigate the clinical outcomes of hematopoietic stem cell transplantation (HSCT) with total body irradiation-based myeloablative conditioning (TBI-MAC) in pediatric patients with acute lymphoblastic leukemia (ALL). We retrospectively examined patients with ALL who underwent HSCT with TBI-MAC from January 2000 to August 2016 at our institute. We enrolled 67 patients with a median follow-up period of 8 years. The 5-year event-free survival (EFS) and overall survival (OS) were 51.2% and 59.6%, respectively. At the first complete remission, HSCT exhibited significantly superior EFS and OS in our patients than that in patients with other diseases. We encountered 57.9% of patients with at least one late complication. Major late complications were short stature (26.3%) and hypogonadism (18.4%). While late complications were observed in several recipients of HSCT, late complication-related deaths occurred in three patients. The TBI-MAC regimen led to favorable clinical outcomes in pediatric patients with ALL who underwent HSCT. Thus, proper evaluation and management of late complications are mandatory.

Resting State Functional Connectivity in Mild Traumatic Brain Injury at the Acute Stage: Independent Component and Seed-Based Analyses

PubMed Central

Iraji, Armin; Benson, Randall R.; Welch, Robert D.; O'Neil, Brian J.; Woodard, John L.; Imran Ayaz, Syed; Kulek, Andrew; Mika, Valerie; Medado, Patrick; Soltanian-Zadeh, Hamid; Liu, Tianming; Haacke, E. Mark

2015-01-01

Abstract Mild traumatic brain injury (mTBI) accounts for more than 1 million emergency visits each year. Most of the injured stay in the emergency department for a few hours and are discharged home without a specific follow-up plan because of their negative clinical structural imaging. Advanced magnetic resonance imaging (MRI), particularly functional MRI (fMRI), has been reported as being sensitive to functional disturbances after brain injury. In this study, a cohort of 12 patients with mTBI were prospectively recruited from the emergency department of our local Level-1 trauma center for an advanced MRI scan at the acute stage. Sixteen age- and sex-matched controls were also recruited for comparison. Both group-based and individual-based independent component analysis of resting-state fMRI (rsfMRI) demonstrated reduced functional connectivity in both posterior cingulate cortex (PCC) and precuneus regions in comparison with controls, which is part of the default mode network (DMN). Further seed-based analysis confirmed reduced functional connectivity in these two regions and also demonstrated increased connectivity between these regions and other regions of the brain in mTBI. Seed-based analysis using the thalamus, hippocampus, and amygdala regions further demonstrated increased functional connectivity between these regions and other regions of the brain, particularly in the frontal lobe, in mTBI. Our data demonstrate alterations of multiple brain networks at the resting state, particularly increased functional connectivity in the frontal lobe, in response to brain concussion at the acute stage. Resting-state functional connectivity of the DMN could serve as a potential biomarker for improved detection of mTBI in the acute setting. PMID:25285363

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

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

Acute Serum Hormone Levels: Characterization and Prognosis after Severe Traumatic Brain Injury

PubMed Central

McCullough, Emily H.; Niyonkuru, Christian; Ozawa, Haishin; Loucks, Tammy L.; Dobos, Julie A.; Brett, Christopher A.; Santarsieri, Martina; Dixon, C. Edward; Berga, Sarah L.; Fabio, Anthony

2011-01-01

Abstract Experimental traumatic brain injury (TBI) studies report the neuroprotective effects of female sex steroids on multiple mechanisms of injury, with the clinical assumption that women have hormonally mediated neuroprotection because of the endogenous presence of these hormones. Other literature indicates that testosterone may exacerbate injury. Further, stress hormone abnormalities that accompany critical illness may both amplify or blunt sex steroid levels. To better understand the role of sex steroid exposure in mediating TBI, we 1) characterized temporal profiles of serum gonadal and stress hormones in a population with severe TBI during the acute phases of their injury; and 2) used a biological systems approach to evaluate these hormones as biomarkers predicting global outcome. The study population was 117 adults (28 women; 89 men) with severe TBI. Serum samples (n=536) were collected for 7 days post-TBI for cortisol, progesterone, testosterone, estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Hormone data were linked with clinical data, including acute care mortality and Glasgow Outcome Scale (GOS) scores at 6 months. Hormone levels after TBI were compared to those in healthy controls (n=14). Group based trajectory analysis (TRAJ) was used to develop temporal hormone profiles that delineate distinct subpopulations in the cohort. Structural equations models were used to determine inter-relationships between hormones and outcomes within a multivariate model. Compared to controls, acute serum hormone levels were significantly altered after severe TBI. Changes in the post-TBI adrenal response and peripheral aromatization influenced hormone TRAJ profiles and contributed to the abnormalities, including increased estradiol in men and increased testosterone in women. In addition to older age and greater injury severity, increased estradiol and testosterone levels over time were associated with increased mortality and worse global

Effects of transcranial LED therapy on the cognitive rehabilitation for diffuse axonal injury due to severe acute traumatic brain injury: study protocol for a randomized controlled trial.

PubMed

Santos, João Gustavo Rocha Peixoto Dos; Zaninotto, Ana Luiza Costa; Zângaro, Renato Amaro; Carneiro, Ana Maria Costa; Neville, Iuri Santana; de Andrade, Almir Ferreira; Teixeira, Manoel Jacobsen; Paiva, Wellingson Silva

2018-04-24

Photobiomodulation describes the use of red or near-infrared light to stimulate or regenerate tissue. It was discovered that near-infrared wavelengths (800-900 nm) and red (600 nm) light-emitting diodes (LED) are able to penetrate through the scalp and skull and have the potential to improve the subnormal cellular activity of compromised brain tissue. Different experimental and clinical studies were performed to test LED therapy for traumatic brain injury (TBI) with promising results. One of the proposals of this present study is to develop different approaches to maximize the positive effects of this therapy and improve the quality of life of TBI patients. This is a double-blinded, randomized, controlled trial of patients with diffuse axonal injury (DAI) due to a severe TBI in an acute stage (less than 8 h). Thirty two patients will be randomized to active coil helmet and inactive coil (sham) groups in a 1:1 ratio. The protocol includes 18 sessions of transcranial LED stimulation (627 nm, 70 mW/cm 2 , 10 J/cm 2 ) at four points of the frontal and parietal regions for 30 s each, totaling 120 s, three times per week for 6 weeks, lasting 30 min. Patients will be evaluated with the Glasgow Outcome Scale Extended (GOSE) before stimulation and 1, 3, and 6 months after the first stimulation. The study hypotheses are as follows: (1) transcranial LED therapy (TCLT) will improve the cognitive function of DAI patients and (2) TCLT will promote beneficial hemodynamic changes in cerebral circulation. This study evaluates early and delayed effects of TCLT on the cognitive rehabilitation for DAI following severe acute TBI. There is a paucity of studies regarding the use of this therapy for cognitive improvement in TBI. There are some experimental studies and case series presenting interesting results for TBI cognitive improvement but no clinical trials. ClinicalTrials.gov, NCT03281759 . Registered on 13 September 2017.

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 ...

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY DISEASE STATE CLINICAL REVIEW: A NEUROENDOCRINE APPROACH TO PATIENTS WITH TRAUMATIC BRAIN INJURY.

PubMed

Tritos, Nicholas A; Yuen, Kevin C J; Kelly, Daniel F

2015-07-01

Traumatic brain injury (TBI) is now recognized as a major public health concern in the United States and is associated with substantial morbidity and mortality in both children and adults. Several lines of evidence indicate that TBI-induced hypopituitarism is not infrequent in TBI survivors and may contribute to the burden of illness in this population. The goal of this article is to review the published data and propose an approach for the neuroendocrine evaluation and management of these patients. To identify pertinent articles, electronic literature searches were conducted using the following keywords: "traumatic brain injury," "pituitary," "hypopituitarism," "growth hormone deficiency," "hypogonadism," "hypoadrenalism," and "hypothyroidism." Relevant articles were identified and considered for inclusion in the present article. TBI-induced hypopituitarism appears to be more common in patients with severe TBI. However, patients with mild TBI or those with repeated, sports-, or blast-related TBI are also at risk for hypopituitarism. Deficiencies of growth hormone and gonadotropins appear to be most common and have been associated with increased morbidity in this population. A systematic approach is advised in order to establish the presence of pituitary hormone deficiencies and implement appropriate replacement therapies. The presence of traumatic hypopituitarism should be considered during the acute phase as well as during the rehabilitation phase of patients with TBI. All patients with moderate to severe TBI require evaluation of pituitary function. In addition, symptomatic patients with mild TBI and impaired quality of life are at risk for hypopituitarism and should be offered neuroendocrine testing.

Acute and long-term pituitary insufficiency in traumatic brain injury: a prospective single-centre study.

PubMed

Klose, M; Juul, A; Struck, J; Morgenthaler, N G; Kosteljanetz, M; Feldt-Rasmussen, U

2007-10-01

To assess the prevalence of hypopituitarism following traumatic brain injury (TBI), describe the time-course and assess the association with trauma-related parameters and early post-traumatic hormone alterations. A 12-month prospective study. Forty-six consecutive patients with TBI (mild: N = 22; moderate: N = 9; severe: N = 15). Baseline and stimulated hormone concentrations were assessed in the early phase (0-12 days post-traumatically), and at 3, 6 and 12 months postinjury. Pituitary tests included the Synacthen-test (acute +6 months) and the insulin tolerance test (ITT) or the GHRH + arginine test if the ITT was contraindicated (3 + 12 months). Insufficiencies were confirmed by retesting. Early post-traumatic hormone alterations mimicking central hypogonadism or hypothyroidism were present in 35 of the 46 (76%) patients. Three months post-traumatically, 6 of the 46 patients failed anterior pituitary testing. At 12 months, one patient had recovered, whereas none developed new insufficiencies. All insufficient patients had GH deficiency (5 out of 46), followed by ACTH- (3 out of 46), TSH- (1 out of 46), LH/FSH- (1 out of 46) and ADH deficiency (1 out of 46). Hypopituitary patients had more frequently been exposed to severe TBI (4 out of 15) than to mild or moderate TBI (1 out of 31) (P = 0.02). Early endocrine alterations including lowered thyroid and gonadal hormones, and increased total cortisol, free cortisol and copeptin were positively associated to TBI severity (P < 0.05), but not to long-term development of hypopituitarism (P > 0.1), although it was indicative in some. Long-term hypopituitarism was frequent only in severe TBI. During the 3-12 months follow-up, recovery but no new insufficiencies were recorded, indicating manifest hypothalamic or pituitary damage already a few months postinjury. Very early hormone alterations were not associated to long-term post-traumatic hypopituitarism. Clinicians should, nonetheless, be aware of potential ACTH

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

Imaging Evaluation of Acute Traumatic Brain Injury

PubMed Central

Mutch, Christopher A.; Talbott, Jason F.; Gean, Alisa

2016-01-01

SYNOPSIS Traumatic brain injury (TBI) is a major cause of morbidity and mortality worldwide. Imaging plays an important role in the evaluation, diagnosis, and triage of patients with TBI. Recent studies suggest that it will also help predict patient outcomes. TBI consists of multiple pathoanatomical entities. Here we review the current state of TBI imaging including its indications, benefits and limitations of the modalities, imaging protocols, and imaging findings for each these pathoanatomic entities. We also briefly survey advanced imaging techniques, which include a number of promising areas of TBI research. PMID:27637393

Comparison of Cyclophosphamide Combined with Total Body Irradiation, Oral Busulfan, or Intravenous Busulfan for Allogeneic Hematopoietic Cell Transplantation in Adults with Acute Lymphoblastic Leukemia.

PubMed

Mitsuhashi, Kenjiro; Kako, Shinichi; Shigematsu, Akio; Atsuta, Yoshiko; Doki, Noriko; Fukuda, Takahiro; Kanamori, Heiwa; Onizuka, Makoto; Takahashi, Satoshi; Ozawa, Yukiyasu; Kurokawa, Mineo; Inoue, Yoshiko; Nagamura-Inoue, Tokiko; Morishima, Yasuo; Mizuta, Shuichi; Tanaka, Junji

2016-12-01

We conducted a retrospective analysis to compare outcomes in adult patients with acute lymphoblastic leukemia (ALL) who underwent allogeneic hematopoietic cell transplantation (allo-HCT) with conditioning regimens containing cyclophosphamide (CY) in combination with total body irradiation (TBI), oral busulfan (p.o. BU), or intravenous busulfan (i.v. BU). We used data for January 2000 to December 2012 from the Transplant Registry Unified Management Program of the Japan Society of Hematopoietic Cell Transplantation. We identified 2130 patients treated with TBI/CY (n = 2028), p.o. BU/CY (n = 60), or i.v. BU/CY (n = 42). Two-year overall survival (OS) and 2-year relapse-free survival rates were 69.0% and 62.1%, respectively, in the TBI/CY group, 55.9% and 54.2% in the p.o. BU/CY group, and 71.0% and 46.8% in the i.v. BU/CY group. In multivariate analysis, compared with TBI/CY, p.o. BU/CY, but not i.v. BU/CY, was associated with lower OS (hazard ratio [HR], 1.46; P = .047) and a higher incidence of sinusoidal obstruction syndrome (HR, 3.36; P = .030). No between-group differences were seen in the incidence of nonrelapse mortality, relapse, acute graft-versus-host disease (GVHD), or chronic GVHD. We suggest that i.v. BU/CY might be a possible alternative allo-HCT conditioning regimen for adults with ALL who are not suitable for TBI. Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. 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.

Endocrine and metabolic disorders in young adult survivors of childhood acute lymphoblastic leukaemia (ALL) or non-Hodgkin lymphoma (NHL).

PubMed

Steffens, M; Beauloye, V; Brichard, B; Robert, A; Alexopoulou, O; Vermylen, Ch; Maiter, D

2008-11-01

Treatments of acute lymphoblastic leukaemia (ALL) and non-Hodgkin lymphoma (NHL), involving various combinations of chemotherapy (chemo), cranial irradiation (CI) and/or bone marrow transplantation after total body irradiation (BMT/TBI), are often successful but may have several long-term harmful effects. To evaluate late endocrine and metabolic complications in adult survivors of childhood ALL and NHL, in relation with the different therapeutic schemes received. Endocrine and metabolic parameters were determined in 94 patients (48 men, mean age: 24 +/- 5 years) with a former childhood ALL (n = 78) or NHL (n = 16) and subgrouped according to their previous treatment: chemo only (group I; n = 44), chemo + CI (group II; n = 32) and chemo + BMT/TBI (group III; n = 18). Severe GH deficiency (peak < 3.0 ng/ml after glucagon) was observed in 22% and 50% of patients of groups II and III, respectively, while hypothyroidism was mainly observed in group III (56%). Moreover, 83% of men developed hypogonadism after BMT/TBI, compared to 17% and 8% in groups I and II, respectively (P < 0.05), and all grafted women had ovarian failure, in contrast with other female patients in whom menarche had occurred spontaneously. Patients with BMT/TBI had also an adverse metabolic profile, with insulin resistance in 83% and dyslipidaemia in 61%. This study reveals a high prevalence of endocrine and metabolic disorders in young adult survivors of childhood ALL or NHL, this frequency mainly depending on the treatment received. Treatment with BMT/TBI is the most detrimental and many of these patients will develop GHD, hypothyroidism, hypogonadism, insulin resistance and dyslipidaemia.

Acute and chronically increased immunoreactivity to phosphorylation-independent but not pathological TDP-43 after a single traumatic brain injury in humans

PubMed Central

Johnson, Victoria E.; Stewart, William; Trojanowski, John Q.

2012-01-01

The pathologic phosphorylation and sub-cellular translocation of neuronal transactive response-DNA binding protein (TDP-43) was identified as the major disease protein in frontotemporal lobar degeneration (FTLD) with ubiquitinated inclusions, now termed FTLD-TDP, and amyotrophic lateral sclerosis (ALS). More recently, TDP-43 proteinopathy has been reported in dementia pugilistica or chronic traumatic encephalopathy caused by repetitive traumatic brain injury (TBI). While a single TBI has been linked to the development of Alzheimer’s disease and an increased frequency of neurofibrillary tangles, TDP-43 proteinopathy has not been examined with survival following a single TBI. Using immunohistochemistry specific for both pathological phosphorylated TDP-43 (p-TDP-43) and phosphorylation-independent TDP-43 (pi-TDP-43), we examined acute (n = 23: Survival < 2 weeks) and long-term (n = 39; 1–47 years survival) survivors of a single TBI versus age-matched controls (n = 47). Multiple regions were examined including the hippocampus, medial temporal lobe, cingulate gyrus, superior frontal gyrus and brainstem. No association was found between a history of single TBI and abnormally phosphorylated TDP-43 (p-TDP-43) inclusions. Specifically, just 3 of 62 TBI cases displayed p-TDP-43 pathology versus 2 of 47 control cases. However, while aggregates of p-TDP-43 were not increased acutely or long-term following TBI, immunoreactivity to phosphorylation-independent TDP-43 was commonly increased in the cytoplasm following TBI with both acute and long-term survival. Moreover, while single TBI can induce multiple long-term neurodegenerative changes, the absence of TDP-43 proteinopathy may indicate a fundamental difference in the processes induced following single TBI from those of repetitive TBI. PMID:22101322

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

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,…

Deletion of aquaporin-4 is neuroprotective during the acute stage of micro traumatic brain injury in mice.

PubMed

Liang, Fengyin; Luo, Chuanming; Xu, Guangqing; Su, Fengjuan; He, Xiaofei; Long, Simei; Ren, Huixia; Liu, Yaning; Feng, Yanqing; Pei, Zhong

2015-06-26

Micro traumatic brain injury (TBI) is the most common type of brain injury, but the mechanisms underlying it are poorly understood. Aquaporin-4 (AQP4) is a water channel expressed in astrocyte end-feet, which plays an important role in brain edema. However, little is known about the role of AQP4 in micro TBI. Here, we examined the role of AQP4 in the pathogenesis of micro TBI in a closed-skull brain injury model, using two-photon microscopy. Our results indicate that AQP4 deletion reduced cell death, water content, astrocyte swelling and lesion volume during the acute stage of micro TBI. Our data revealed that astrocyte swelling is a decisive pathophysiological factor in the acute phase of this form of micro brain injury. Thus, treatments that inhibit AQP4 could be used as a neuroprotective strategy for micro TBI. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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.

Citicoline for traumatic brain injury: a systematic review & meta-analysis.

PubMed

Meshkini, Ali; Meshkini, Mohammad; Sadeghi-Bazargani, Homayoun

2017-01-01

Traumatic Brain Injury (TBI) is the leading cause of mortality and morbidity especially in young ages. Despite over 30 years of using Neuroprotective agents for TBI management, there is no absolute recommended agent for the condition yet. This study is a part of a scoping review thesis on "Neuroprotective agents using for Traumatic Brain Injury: a systematic review & meta-analyses", which had a wide proposal keywords and ran in "Cochrane CENTRAL", "MedLine/PubMed", "SCOPUS", "Thomson Reuters Web of Science", "SID.ir", "Barket Foundation", and "clinicaltrials.gov" databases up to September 06, 2015. This study limits the retrieved search results only to those which used citicoline for TBI management. The included Randomized Clinical Trials' (RCTs) were assessed for their quality of reporting by adapting CONSORT-checklist prior to extracting their data into me-ta-analysis. Meta-analyses of this review were conducted by Glasgow Outcome Scale (GOS) in acute TBI patients and total neuropsychological assessments in both acute and chronic TBI management, mortalities and adverse-effects. Four RCTs were retrieved and included in this review with 1196 participants (10 were chronic TBI impaired patients); the analysis of 1128 patients for their favorable GOS outcomes in two studies showed no significant difference between the study groups; however, neuropsychological outcomes were significantly better in placebo/control group of 971 patients of three studies. Mortality rates and adverse-effects analysis based on two studies with 1429 patients showed no significant difference between the study groups. However, two other studies have neither mortality nor adverse effects reports due to their protocol. Citicoline use for acute TBI seems to have no field of support anymore, whereas it may have some benefits in improving the neuro-cognitive state in chronic TBI patients. It's also recommended to keep in mind acute interventions like Psychological First Aid (PFA) during acute TBI

Barriers to Nutrition Intervention for Patients With a Traumatic Brain Injury: Views and Attitudes of Medical and Nursing Practitioners in the Acute Care Setting.

PubMed

Chapple, Lee-Anne; Chapman, Marianne; Shalit, Natalie; Udy, Andrew; Deane, Adam; Williams, Lauren

2018-02-01

Nutrition delivered to patients with a traumatic brain injury (TBI) is typically below prescribed amounts. While the dietitian plays an important role in the assessment and provision of nutrition needs, they are part of a multidisciplinary team. The views and attitudes of medical and nursing practitioners are likely to be crucial to implementation of nutrition to patients with TBI, but there is limited information describing these. A qualitative exploratory approach was used to explore the views and attitudes of medical and nursing practitioners on nutrition for patients with TBI. Participants at 2 major neurotrauma hospitals in Australia completed individual semi-structured interviews with a set of questions and a case study. Interviews were transcribed and coded for themes. Thirty-four health practitioners participated: 18 nurses and 16 physicians. Three major themes emerged: (1) nutrition practices over the hospital admission reflect the recovery course, (2) there are competing priorities when caring for patients with TBI, and (3) the implementation of nutrition therapy is influenced by practitioner roles and expectations. Use of qualitative inquiry in the study of attitudes toward nutrition provision to patients with TBI provided detailed insights into the challenges of operationalizing nutrition therapy. These insights can be used to clarify communication between health practitioners working with patients with TBI across the continuum of care. © 2017 American Society for Parenteral and Enteral Nutrition.

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

Comparison of Glasgow Coma Scale, Full Outline of Unresponsiveness and Acute Physiology and Chronic Health Evaluation in Prediction of Mortality Rate Among Patients With Traumatic Brain Injury Admitted to Intensive Care Unit

PubMed Central

Hosseini, Seyed Hossein; Ayyasi, Mitra; Akbari, Hooshang; Heidari Gorji, Mohammad Ali

2016-01-01

Background Traumatic brain injury (TBI) is a common cause of mortality and disability worldwide. Choosing an appropriate diagnostic tool is critical in early stage for appropriate decision about primary diagnosis, medical care and prognosis. Objectives This study aimed to compare the Glasgow coma scale (GCS), full outline of unresponsiveness (FOUR) and acute physiology and chronic health evaluation (APACHE II) with respect to prediction of the mortality rate of patients with TBI admitted to intensive care unit. Patients and Methods This diagnostic study was conducted on 80 patients with TBI in educational hospitals. The scores of APACHE II, GCS and FOUR were recorded during the first 24 hours of admission of patients. In this study, early mortality means the patient death before 14 days and delayed mortality means the patient death 15 days after admitting to hospital. The collected data were analyzed using descriptive and inductive statistics. Results The results showed that the mean age of the patients was 33.80 ± 12.60. From a total of 80 patients with TBI, 16 (20%) were females and 64 (80%) males. The mortality rate was 15 (18.7%). The results showed no significant difference among three tools. In prediction of early mortality, the areas under the curve (AUCs) were 0.92 (CI = 0.95. 0.81 - 0.97), 0.90 (CI = 0.95. 0.74 - 0.94), and 0.96 (CI = 0.95. 0.87 - 0.9) for FOUR, APACHE II and GCS, respectively. In delayed mortality, the AUCs were 0.89 (CI = 0.95. 0.81-0.94), 0.94 (CI = 0.95. 0.74 - 0.97) and 0.90 (CI = 0.95. 0.87 - 0.95) for FOUR, APACHE II and GCS, respectively. Conclusions Considering that GCS is easy to use and the FOUR can diagnose a locking syndrome along same values of subscales. These two subscales are superior to APACHI II in prediction of early mortality. Conversation APACHE II is more punctual in the prediction of delayed mortality. PMID:29696116

The Role of Neurogenic Inflammation in Blood-Brain Barrier Disruption and Development of Cerebral Oedema Following Acute Central Nervous System (CNS) Injury

PubMed Central

Sorby-Adams, Annabel J.; Marcoionni, Amanda M.; Dempsey, Eden R.; Woenig, Joshua A.; Turner, Renée J.

2017-01-01

Acute central nervous system (CNS) injury, encompassing traumatic brain injury (TBI) and stroke, accounts for a significant burden of morbidity and mortality worldwide, largely attributable to the development of cerebral oedema and elevated intracranial pressure (ICP). Despite this, clinical treatments are limited and new therapies are urgently required to improve patient outcomes and survival. Originally characterised in peripheral tissues, such as the skin and lungs as a neurally-elicited inflammatory process that contributes to increased microvascular permeability and tissue swelling, neurogenic inflammation has now been described in acute injury to the brain where it may play a key role in the secondary injury cascades that evolve following both TBI and stroke. In particular, release of the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) appear to be critically involved. In particular, increased SP expression is observed in perivascular tissue following acute CNS injury, with the magnitude of SP release being related to both the frequency and degree of the insult. SP release is associated with profound blood-brain barrier disruption and the subsequent development of vasogenic oedema, as well as neuronal injury and poor functional outcomes. Inhibition of SP through use of a neurokinin 1 (NK1) antagonist is highly beneficial following both TBI and ischaemic stroke in pre-clinical models. The role of CGRP is more unclear, especially with respect to TBI, with both elevations and reductions in CGRP levels reported following trauma. However, a beneficial role has been delineated in stroke, given its potent vasodilatory effects. Thus, modulating neuropeptides represents a novel therapeutic target in the treatment of cerebral oedema following acute CNS injury. PMID:28817088

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

Impact on long-term OS of conditioning regimen in allogeneic BMT for children with AML in first CR: TBI+CY versus BU+CY: a report from the Société Française de Greffe de Moelle et de Thérapie Cellulaire.

PubMed

de Berranger, E; Cousien, A; Petit, A; Peffault de Latour, R; Galambrun, C; Bertrand, Y; Salmon, A; Rialland, F; Rohrlich, P-S; Vannier, J-P; Lutz, P; Yakouben, K; Duhamel, A; Bruno, B; Michel, G; Dalle, J-H

2014-03-01

Allogeneic hematopoietic SCT (HSCT) appears to be an efficient tool to cure high-risk AML in first CR but the choice between BU-based or TBI-based conditioning regimens still remains controversial. In order to analyze the impact of conditioning regimen on long-term survival, we conducted a retrospective analysis from French registry data including all consecutive patients under 18 years old (n=226) from 1980 to 2004 transplanted for AML in CR1 from sibling (n=142) or matched unrelated donors and given either TBI-1200 cGy and CY 120 mg/kg (TBI-Cy, n=84) or BU 16 mg/kg and CY 200 mg/kg (BuCy200, n=142). Patient subgroups were comparable for all criteria except for median age at diagnosis and HSCT and for donor type. Both 5-year OS and disease-free survival (DFS) were significantly better in BuCy200 group (P=0.02 and 0.005, respectively). In multivariate analysis, both HLA matching and BuCy200 appeared as good prognostic factors for treatment-related mortality and DFS. Grade 2-4 acute GvHD and chronic GvHD rates were statistically higher in TBI-Cy group than in Bu-Cy200 one with a RR at 2 (P=0.002). In total, Bu-Cy200 conditioning regimen gives better outcome compared with TBI-Cy irrespective of the stem cell source and the donor type.

Efficacy of Progesterone for Acute Traumatic Brain Injury: a Meta-analysis of Randomized Controlled Trials.

PubMed

Wang, Zhen; Shi, LiGen; Ding, Wu; Shao, FangJie; Yu, Jun; Zhang, Jianmin

2016-12-01

Progesterone, a steroid hormone, has been shown to have multifactorial neuroprotective effects in a variety of animal models of acute traumatic brain injury (TBI). Translation to humans showed positive effects in previous phase II trials, but unfortunately, negative results were observed in two recent phase III trials. The present study focuses on the efficacy of progesterone on acute TBI based on the published data of randomized controlled trials (RCTs). MEDLINE, EMBASE, and Cochrane Library were used to search from January 1980 to August 2015 for English language studies. The primary outcome was a favorable outcome in the Glasgow outcome scale (GOS). The secondary outcomes included mortality and adverse events. A total of 2396 patients from 5 RCTs were included in the present study. There were no significant differences in favorable outcome (relative risk (RR) 1.07, 95 % confidence interval (CI) 0.91 to 1.27, P = 0.41) and mortality rate (RR 0.85, 95 % CI 0.65 to 1.13, P = 0.27) between progesterone and placebo groups. In a subgroup analysis, favorable outcome (RR 1.45, 95 % CI 1.11 to 1.89, P = 0.007) and decreased mortality rate (RR 0.58, 95 % CI 0.41 to 0.84, P = 0.004) are only observed in the phase II RCTs. The included factors were the severity of TBI, method of drug administration, and duration of observation and had no influence on the observed outcomes. Sensitivity analysis showed that all the outcomes were stable after excluding Shakeri (Clin Neurol Neurosurg 115: 2019-2022, 2013) or Wright (N Engl J Med 371: 2457-2466, 2014) trials. The quality of the evidence was varied from high to low. In conclusion, progesterone has no significant improvement in the functional recovery and mortality rate after acute TBI.

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

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

Demographic profile and extent of healthcare resource utilisation of patients with severe traumatic brain injury: still a major public health problem.

PubMed

Wee, Jing Zhong; Yang, Yun Rui Jasmine; Lee, Qian Yi Ruth; Cao, Kelly; Chong, Chin Ted

2016-09-01

Trauma is the fifth principal cause of death in Singapore, with traumatic brain injury (TBI) being the leading specific subordinate cause. This study was an eight-year retrospective review of the demographic profiles of patients with severe TBI who were admitted to the neurointensive care unit (NICU) of the National Neuroscience Institute at Tan Tock Seng Hospital, Singapore, between 2004 and 2011. A total of 780 TBI patients were admitted during the study period; 365 (46.8%) patients sustained severe TBI (i.e. Glasgow Coma Scale score ≤ 8), with the majority (75.3%) being male. The ages of patients with severe TBI ranged from 14-93 years, with a bimodal preponderance in young adults (i.e. 21-40 years) and elderly persons (i.e. > 60 years). Motor vehicle accidents (48.8%) and falls (42.5%) were the main mechanisms of injury. Invasive line monitoring was frequently employed; invasive arterial blood pressure monitoring and central venous pressure monitoring were used in 81.6% and 60.0% of the patients, respectively, while intracranial pressure (ICP) measurement was required in 47.4% of the patients. The use of tiered therapy to control ICP (e.g. sedation, osmotherapy, cerebrospinal fluid drainage, moderate hyperventilation and barbiturate-induced coma) converged with international practices. The high-risk groups for severe TBI were young adults and elderly persons involved in motor vehicle accidents and falls, respectively. In the NICU, the care of patients with severe TBI requires heavy utilisation of resources. The healthcare burden of these patients extends beyond the acute critical care phase.

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.

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

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

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

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

Investigating Metacognition, Cognition, and Behavioral Deficits of College Students with Acute Traumatic Brain Injuries

ERIC Educational Resources Information Center

Martinez, Sarah; Davalos, Deana

2016-01-01

Objective: Executive dysfunction in college students who have had an acute traumatic brain injury (TBI) was investigated. The cognitive, behavioral, and metacognitive effects on college students who endorsed experiencing a brain injury were specifically explored. Participants: Participants were 121 college students who endorsed a mild TBI, and 121…

Outcome of Acute Pancreatic and Peripancreatic Collections Occurring in Patients With Acute Pancreatitis.

PubMed

Manrai, Manish; Kochhar, Rakesh; Gupta, Vikas; Yadav, Thakur Deen; Dhaka, Narendra; Kalra, Naveen; Sinha, Saroj K; Khandelwal, Niranjan

2018-02-01

To study the outcome of acute collections occurring in patients with acute pancreatitis BACKGROUND:: There are limited data on natural history of acute collections arising after acute pancreatitis (AP). Consecutive patients of AP admitted between July 2011 and December 2012 were evaluated by imaging for development of acute collections as defined by revised Atlanta classification. Imaging was repeated at 1 and 3 months. Spontaneous resolution, evolution, and need for intervention were assessed. Of the 189 patients, 151 patients (79.9%) had acute collections with severe disease and delayed hospitalization being predictors of acute collections. Thirty-six patients had acute interstitial edematous pancreatitis, 8 of whom developed acute peripancreatic fluid collections, of which 1 evolved into pseudocyst. Among the 153 patients with acute necrotizing pancreatitis, 143 (93.4%) developed acute necrotic collection (ANC). Twenty-three of 143 ANC patients died, 21 had resolved collections, whereas 84 developed walled-off necrosis (WON), with necrosis >30% (P = 0.010) and Computed Tomographic Severity Index score ≥7 (P = 0.048) predicting development of WON. Of the 84 patients with WON, 8 expired, 53 patients required an intervention, and 23 were managed conservatively. Independent predictors of any intervention among all patients were Computed Tomographic Severity Index score ≥7 (P < 0.001) and interval between onset of pain to hospitalization >7 days (P = 0.04). Patients with severe AP and delayed hospitalization more often develop acute collections. Pancreatic pseudocysts are a rarity in acute interstitial pancreatitis. A majority of patients with necrotising pancreatitis will develop ANC, more than half of whom will develop WON. Delay in hospitalization and higher baseline necrosis score predict need for intervention.

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

The Development and Psychometric Evaluation of a Supplementary Index Score of the Neuropsychological Assessment Battery Screening Module that is Sensitive to Traumatic Brain Injury.

PubMed

Hacker, David; Jones, Christopher A; Clowes, Zoe; Belli, Antonio; Su, Zhangjie; Sitaraman, Murugan; Davies, David; Taylor, Ross; Flahive, Elizabeth; Travis, Clare; O'Neil, Nicci; Pettigrew, Yvonne

2017-03-01

This study examines the validity of the NAB Screening Module (screening module of the neuropsychological assessment battery, S-NAB) in an acute traumatic brain injury (TBI) inpatient population and provides psychometric evaluation of an original index sensitive to TBI impairment. The utility of the S-NAB as a TBI screen was examined using a between groups design. One-hundred and four patients with mild complicated to severe TBI were recruited from a consecutive cohort of patients admitted as inpatients to a UK Major Trauma Centre. Ninety-eight control participants were selected from the S-NAB normative sample. All TBI patients completed the S-NAB during their inpatient stay. Control participants scored significantly higher than TBI participants on the Total Screening index (t = 3.626, p < 0.01), The Attention index (t = 7.882, p < 0.01), and the Executive index (t = 5.577, p < 0.01). A briefer TBI Impairment index of six subtests was constructed which accurately discriminated TBI patients from normative controls (t = 9.9, p < 0.01; Cohen's d = 1.54). The TBI index had excellent classification accuracy (AUC = 0.83), superior to that of the standard S-NAB indices. The TBI Index, Attention Index, and Total Screening Index demonstrated increasing impairment with increased severity of injury. The S-NAB TBI index is a robust, reliable screening index for use with acute TBI patients, which is sensitive to the effects of acute TBI. It affords a briefer cognitive screen than the S-NAB and demonstrates a dose response relationship to TBI severity. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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.

High-frequency oscillation and tracheal gas insufflation in patients with severe acute respiratory distress syndrome and traumatic brain injury: an interventional physiological study

PubMed Central

2013-01-01

Introduction In acute respiratory distress syndrome (ARDS), combined high-frequency oscillation (HFO) and tracheal gas insufflation (TGI) improves gas exchange compared with conventional mechanical ventilation (CMV). We evaluated the effect of HFO-TGI on PaO2/fractional inspired O2 (FiO2) and PaCO2, systemic hemodynamics, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) in patients with traumatic brain injury (TBI) and concurrent severe ARDS. Methods We studied 13 TBI/ARDS patients requiring anesthesia, hyperosmolar therapy, and ventilation with moderate-to-high CMV-tidal volumes for ICP control. Patients had PaO2/FiO2 <100 mm Hg at end-expiratory pressure ≥10 cm H2O. Patients received consecutive, daily, 12-hour rescue sessions of HFO-TGI interspersed with 12-hour periods of CMV. HFO-TGI was discontinued when the post-HFO-TGI PaO2/FiO2 exceeded 100 mm Hg for >12 hours. Arterial/central-venous blood gases, hemodynamics, and ICP were recorded before, during (every 4 hours), and after HFO-TGI, and were analyzed by using repeated measures analysis of variance. Respiratory mechanics were assessed before and after HFO-TGI. Results Each patient received three to four HFO-TGI sessions (total sessions, n = 43). Pre-HFO-TGI PaO2/FiO2 (mean ± standard deviation (SD): 83.2 ± 15.5 mm Hg) increased on average by approximately 130% to163% during HFO-TGI (P < 0.01) and remained improved by approximately 73% after HFO-TGI (P < 0.01). Pre-HFO-TGI CMV plateau pressure (30.4 ± 4.5 cm H2O) and respiratory compliance (37.8 ± 9.2 ml/cm H2O), respectively, improved on average by approximately 7.5% and 20% after HFO-TGI (P < 0.01 for both). During HFO-TGI, systemic hemodynamics remained unchanged. Transient improvements were observed after 4 hours of HFO-TGI versus pre-HFO-TGI CMV in PaCO2 (37.7 ± 9.9 versus 41.2 ± 10.8 mm Hg; P < 0.01), ICP (17.2 ± 5.4 versus 19.7 ± 5.9 mm Hg; P < 0.05), and CPP (77.2 ± 14.6 versus 71.9 ± 14.8 mm Hg; P < 0.05). Conclusions

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.

Acute over-the-counter pharmacological intervention does not adversely affect behavioral outcome following diffuse traumatic brain injury in the mouse.

PubMed

Harrison, Jordan L; Rowe, Rachel K; O'Hara, Bruce F; Adelson, P David; Lifshitz, Jonathan

2014-09-01

Following mild traumatic brain injury (TBI), patients may self-treat symptoms of concussion, including post-traumatic headache, taking over-the-counter (OTC) analgesics. Administering one dose of OTC analgesics immediately following experimental brain injury mimics the at-home treated population of concussed patients and may accelerate the understanding of the relationship between brain injury and OTC pharmacological intervention. In the current study, we investigate the effect of acute administration of OTC analgesics on neurological function and cortical cytokine levels after experimental diffuse TBI in the mouse. Adult, male C57BL/6 mice were injured using a midline fluid percussion (mFPI) injury model of concussion (6-10 min righting reflex time for brain-injured mice). Experimental groups included mFPI paired with either ibuprofen (60 mg/kg, i.p.; n = 16), acetaminophen (40 mg/kg, i.p.; n = 9), or vehicle (15% ethanol (v/v) in 0.9% saline; n = 13) and sham injury paired OTC medicine or vehicle (n = 7-10 per group). At 24 h after injury, functional outcome was assessed using the rotarod task and a modified neurological severity score. Following behavior assessment, cortical cytokine levels were measured by multiplex ELISA at 24 h post-injury. To evaluate efficacy on acute inflammation, cortical cytokine levels were measured also at 6 h post-injury. In the diffuse brain-injured mouse, immediate pharmacological intervention did not attenuate or exacerbate TBI-induced functional deficits. Cortical cytokine levels were affected by injury, time, or their interaction. However, levels were not affected by treatment at 6 or 24 h post-injury. These data indicate that acute administration of OTC analgesics did not exacerbate or attenuate brain-injury deficits which may inform clinical recommendations for the at-home treated mildly concussed patient.

Acute Assessment of Traumatic Brain Injury and Post-Traumatic Stress After Exposure to a Deployment-Related Explosive Blast.

PubMed

Baker, Monty T; Moring, John C; Hale, Willie J; Mintz, Jim; Young-McCaughan, Stacey; Bryant, Richard A; Broshek, Donna K; Barth, Jeffrey T; Villarreal, Robert; Lancaster, Cynthia L; Malach, Steffany L; Lara-Ruiz, Jose M; Isler, William; Peterson, Alan L

2018-05-18

Traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) are two of the signature injuries in military service members who have been exposed to explosive blasts during deployments to Iraq and Afghanistan. Acute stress disorder (ASD), which occurs within 2-30 d after trauma exposure, is a more immediate psychological reaction predictive of the later development of PTSD. Most previous studies have evaluated service members after their return from deployment, which is often months or years after the initial blast exposure. The current study is the first large study to collect psychological and neuropsychological data from active duty service members within a few days after blast exposure. Recruitment for blast-injured TBI patients occurred at the Air Force Theater Hospital, 332nd Air Expeditionary Wing, Joint Base Balad, Iraq. Patients were referred from across the combat theater and evaluated as part of routine clinical assessment of psychiatric and neuropsychological symptoms after exposure to an explosive blast. Four measures of neuropsychological functioning were used: the Military Acute Concussion Evaluation (MACE); the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS); the Headminder Cognitive Stability Index (CSI); and the Automated Neuropsychological Assessment Metrics, Version 4.0 (ANAM4). Three measures of combat exposure and psychological functioning were used: the Combat Experiences Scale (CES); the PTSD Checklist-Military Version (PCL-M); and the Acute Stress Disorder Scale (ASDS). Assessments were completed by a deployed clinical psychologist, clinical social worker, or mental health technician. A total of 894 patients were evaluated. Data from 93 patients were removed from the data set for analysis because they experienced a head injury due to an event that was not an explosive blast (n = 84) or they were only assessed for psychiatric symptoms (n = 9). This resulted in a total of 801 blast-exposed patients for data

Patient dissatisfaction with acute stroke care.

PubMed

Asplund, Kjell; Jonsson, Fredrik; Eriksson, Marie; Stegmayr, Birgitta; Appelros, Peter; Norrving, Bo; Terént, Andreas; Asberg, Kerstin Hulter

2009-12-01

Riks-Stroke, the Swedish Stroke Register, was used to explore patient characteristics and stroke services as determinants of patient dissatisfaction with acute in-hospital care. All 79 hospitals in Sweden admitting acute stroke patients participate in Riks-Stroke. During 2001 to 2007, 104,876 patients (87% of survivors) responded to a follow-up questionnaire 3 months after acute stroke; this included questions on satisfaction with various aspects of stroke care. The majority (>90%) were satisfied with acute in-hospital stroke care. Dissatisfaction was closely associated with outcome at 3 months. Patient who were dependent regarding activities of daily living, felt depressed, or had poor self-perceived general health were more likely to be dissatisfied. Dissatisfaction with global acute stroke care was linked to dissatisfaction with other aspects of care, including rehabilitation and support by community services. Patients treated in stroke units were less often dissatisfied than patients in general wards, as were patients who had been treated in a small hospital (vs medium or large hospitals) and patient who had participated in discharge planning. In multivariate analyses, the strongest predictor of dissatisfaction with acute care was poor outcome (dependency regarding activities of daily living, depressed mood, poor self-perceived health). Dissatisfaction with in-hospital acute stroke care is part of a more extensive complex comprising poor functional outcome, depressive mood, poor self-perceived general health, and dissatisfaction not only with acute care but also with health care and social services at large. Several aspects of stroke care organization are associated with a lower risk of dissatisfaction.

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

Citicoline for traumatic brain injury: a systematic review & meta-analysis

PubMed Central

Meshkini, Ali; Meshkini, Mohammad; Sadeghi-Bazargani, Homayoun

2017-01-01

Abstract: Background: Traumatic Brain Injury (TBI) is the leading cause of mortality and morbidity especially in young ages. Despite over 30 years of using Neuroprotective agents for TBI management, there is no absolute recommended agent for the condition yet. Methods: This study is a part of a scoping review thesis on "Neuroprotective agents using for Traumatic Brain Injury: a systematic review & meta-analyses", which had a wide proposal keywords and ran in "Cochrane CENTRAL", "MedLine/PubMed", "SCOPUS", "Thomson Reuters Web of Science", "SID.ir", "Barket Foundation", and "clinicaltrials.gov" databases up to September 06, 2015. This study limits the retrieved search results only to those which used \\citicoline for TBI management. The included Randomized Clinical Trials’ (RCTs) were assessed for their quality of reporting by adapting CONSORT-checklist prior to extracting their data into meta-analysis. Meta-analyses of this review were conducted by Glasgow Outcome Scale (GOS) in acute TBI patients and total neuropsychological assessments in both acute and chronic TBI management, mortalities and adverse-effects. Results: Four RCTs were retrieved and included in this review with 1196 participants (10 were chronic TBI impaired patients); the analysis of 1128 patients for their favorable GOS outcomes in two studies showed no significant difference between the study groups; however, neuropsychological outcomes were significantly better in placebo/control group of 971 patients of three studies. Mortality rates and adverse-effects analysis based on two studies with 1429 patients showed no significant difference between the study groups. However, two other studies have neither mortality nor adverse effects reports due to their protocol. Conclusions: Citicoline use for acute TBI seems to have no field of support anymore, whereas it may have some benefits in improving the neuro-cognitive state in chronic TBI patients. It’s also recommended to keep in mind acute

Treosulfan-based conditioning regimens for allogeneic HSCT in children with acute lymphoblastic leukaemia.

PubMed

Boztug, Heidrun; Zecca, Marco; Sykora, Karl-Walter; Veys, Paul; Lankester, Arjan; Slatter, Mary; Skinner, Roderick; Wachowiak, Jacek; Pötschger, Ulrike; Glogova, Evgenia; Peters, Christina

2015-02-01

Standard myeloablative conditioning regimens for children with acute lymphoblastic leukaemia are based on total body irradiation (TBI). However, TBI causes profound short-term and long-term side effects, provoking the necessity for alternative regimens. Treosulfan combines a potent immunosuppressive and antileukaemic effect with myeloablative activity and low toxicity profile. We retrospectively studied toxicity and outcome of 71 paediatric patients with acute lymphoblastic leukaemia (ALL) undergoing haematopoietic stem cell transplantation (HSCT) following treosulfan-based conditioning aiming to identify risk factors for treatment failure and dose-depending outcome differences. Early regimen-related toxicity was low. No case of veno-occlusive disease was reported. There was no association of toxicity with age or number of HSCT. Event-free survival (EFS) of infants was significantly better compared to older children. Overall survival (OS) at 3 years was 51 % and not significantly influenced by number of HSCT (first HSCT 54 %, ≥second HSCT 44 %, p = 0.71). In multivariate analysis, OS and EFS were significantly worse for patients transplanted without complete remission (p = 0.04 and 0.004). Treatment-related mortality was low at 14 %. We conclude that treosulfan-based conditioning is a safe and efficacious approach for paediatric ALL.

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

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

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.

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

Music therapy for early cognitive rehabilitation post-childhood TBI: an intrinsic mixed methods case study.

PubMed

Bower, Janeen; Catroppa, Cathy; Grocke, Denise; Shoemark, Helen

2014-10-01

The primary aim of this case study was to explore the behavioural changes of a paediatric patient in post-traumatic amnesia (PTA) during a music therapy session. A secondary objective was to measure the effect of the music therapy intervention on agitation. Video data from pre, during and post-music therapy sessions were collected and analysed using video micro-analysis and the Agitated Behaviour Scale. The participant displayed four discrete categories of behaviours: Neutral, Acceptance, Recruitment and Rejection. Further analysis revealed brief but consistent and repeated periods of awareness and responsiveness to the live singing of familiar songs, which were classified as Islands of Awareness. Song offered an Environment of Potential to maximise these periods of emerging consciousness. The quantitative data analysis yielded inconclusive results in determining if music therapy was effective in reducing agitation during and immediately post the music therapy sessions. The process of micro-analysis illuminated four discrete participant behaviours not apparent in the immediate clinical setting. The results of this case suggest that the use of familiar song as a music therapy intervention may harness early patient responsiveness to foster cognitive rehabilitation in the early acute phase post-TBI.

Triggering Receptor Expressed on Myeloid Cells 2 Deficiency Alters Acute Macrophage Distribution and Improves Recovery after Traumatic Brain Injury.

PubMed

Saber, Maha; Kokiko-Cochran, Olga; Puntambekar, Shweta S; Lathia, Justin D; Lamb, Bruce T

2017-01-15

Traumatic brain injury (TBI) affects 1.7 million persons annually in the United States (Centers for Disease Control and Prevention). There is increasing evidence that persons exposed to TBI have increased risk of the development of multiple neurodegenerative conditions, including Alzheimer disease (AD). TBI triggers a strong neuroinflammatory response characterized by astrogliosis, activation of microglia, and infiltration of peripheral monocytes. Recent evidence suggests that alterations in innate immunity promote neurodegeneration. This includes genetic studies demonstrating that mutations in triggering receptor expressed on myeloid cells 2 (TREM2) is associated with a higher risk for not only AD but also multiple neurodegenerative diseases. To examine whether TREM2 deficiency affects pathological outcomes of TBI, Trem2 knockout (Trem2 -/- ) and C57BL/6J (B6) mice were given a lateral fluid percussion injury (FPI) and sacrificed at 3 and 120 days post-injury (DPI) to look at both acute and chronic consequences of TREM2 deficiency. Notably, at 3 DPI, B6 mice exposed to TBI exhibited increased expression of TREM2 in the brain. Further, Trem2 -/- mice exposed to TBI exhibited enhanced macrophage activation near the lesion, but significantly less macrophage activation away from the lesion when compared with B6 mice exposed to TBI. In addition, at 120 DPI, Trem2 -/- mice exposed to TBI demonstrated reduced hippocampal atrophy and rescue of TBI-induced behavioral changes when compared with B6 mice exposed to TBI. Taken together, this study suggests that TREM2 deficiency influences both acute and chronic responses to TBI, leading to an altered macrophage response at early time points, and improved pathological and functional outcomes at later time points.

Treo/Flu/TBI With Donor Stem Cell Transplant for Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia

ClinicalTrials.gov

2018-04-16

Acute Myeloid Leukemia in Remission; Chronic Myelomonocytic Leukemia; Minimal Residual Disease; Myelodysplastic Syndrome; Myelodysplastic/Myeloproliferative Neoplasm; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable

Total body irradiation in a patient with fragile X syndrome for acute lymphoblastic leukemia in preparation for stem cell transplantation: A case report and literature review.

PubMed

Collins, D T; Mannina, E M; Mendonca, M

2015-10-01

Fragile X syndrome (FXS) is a congenital disorder caused by expansion of CGG trinucleotide repeat at the 5' end of the fragile X mental retardation gene 1 (FMR1) on the X chromosome that leads to chromosomal instability and diminished serum levels of fragile X mental retardation protein (FMRP). Afflicted individuals often have elongated features, marfanoid habitus, macroorchidism and intellectual impairment. Evolving literature suggests the condition may actually protect from malignancy while chromosomal instability would presumably elevate the risk. Increased sensitivity to ionizing radiation should also be predicted by unstable sites within the DNA. Interestingly, in this report, we detail a patient with FXS diagnosed with acute lymphoblastic leukemia treated with induction followed by subsequent cycles of hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone) with a complete response who then was recommended to undergo peripheral stem cell transplantation. The patient underwent total body irradiation (TBI) as a component of his conditioning regimen and despite the concern of his clinicians, developed minimal acute toxicity and successful engraftment. The pertinent literature regarding irradiation of patients with FXS is also reviewed. © 2015 Wiley Periodicals, Inc.

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

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 ...

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.

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

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.

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

A State-of-the-Science Overview of Randomized Controlled Trials Evaluating Acute Management of Moderate-to-Severe Traumatic Brain Injury

PubMed Central

Synnot, Anneliese; Maas, Andrew I.; Menon, David K.; Cooper, D. James; Rosenfeld, Jeffrey V.; Gruen, Russell L.

2016-01-01

effectiveness research and precision medicine, are needed to fully realize the potential of acute TBI research to benefit patients. PMID:26711675

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.

Traumatic Brain Injury in Young Children: Post-Acute Effects on Cognitive and School Readiness Skills

PubMed Central

Taylor, H. Gerry; Swartwout, Maegan; Yeates, Keith O.; Walz, Nicolay C.; Stancin, Terry; Wade, Shari L.

2009-01-01

Previous studies have documented weaknesses in cognitive ability and early academic readiness in young children with traumatic brain injury (TBI). However, few of these studies have rigorously controlled for demographic characteristics, examined the effects of TBI severity on a wide range of skills, or explored moderating influences of environmental factors on outcomes. To meet these objectives, each of three groups of children with TBI (20 with severe, 64 with moderate, and 15 with mild) were compared with a group of 117 children with orthopedic injuries (OI group). The children were hospitalized for their injuries between 3 and 6 years of age and were assessed an average of 1½ months post injury. Analysis revealed generalized weaknesses in cognitive and school readiness skills in the severe TBI group and suggested less pervasive effects of moderate and mild TBI. Indices of TBI severity predicted outcomes within the TBI sample and environmental factors moderated the effects of TBI on some measures. The findings document adverse effects of TBI in early childhood on post-acute cognitive and school readiness skills and indicate that residual deficits are related to both injury severity and the family environment. PMID:18764969

Hypopituitarism after traumatic brain injury.

PubMed

Bondanelli, Marta; Ambrosio, Maria Rosaria; Zatelli, Maria Chiara; De Marinis, Laura; degli Uberti, Ettore C

2005-05-01

Traumatic brain injury (TBI) is one of the main causes of death and disability in young adults, with consequences ranging from physical disabilities to long-term cognitive, behavioural, psychological and social defects. Post-traumatic hypopituitarism (PTHP) was recognized more than 80 years ago, but it was thought to be a rare occurrence. Recently, clinical evidence has demonstrated that TBI may frequently cause hypothalamic-pituitary dysfunction, probably contributing to a delayed or hampered recovery from TBI. Changes in pituitary hormone secretion may be observed during the acute phase post-TBI, representing part of the acute adaptive response to the injury. Moreover, diminished pituitary hormone secretion, caused by damage to the pituitary and/or hypothalamus, may occur at any time after TBI. PTHP is observed in about 40% of patients with a history of TBI, presenting as an isolated deficiency in most cases, and more rarely as complete pituitary failure. The most common alterations appear to be gonadotropin and somatotropin deficiency, followed by corticotropin and thyrotropin deficiency. Hyper- or hypoprolactinemia may also be present. Diabetes insipidus may be frequent in the early, acute phase post-TBI, but it is rarely permanent. Severity of TBI seems to be an important risk factor for developing PTHP; however, PTHP can also manifest after mild TBI. Accurate evaluation and long-term follow-up of all TBI patients are necessary in order to detect the occurrence of PTHP, regardless of clinical evidence for pituitary dysfunction. In order to improve outcome and quality of life of TBI patients, an adequate replacement therapy is of paramount importance.

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

predicted by the structural deficits, not only within the primary sensorimotor injury site and pericontused regions, but the normally connected homotopic cortex, as well as subcortical regions, all of which persisted chronically. Especially novel in this study is the unanticipated finding of widespread increases in connection strength that dwarf both the degree and extent of the functional disconnections, and which persist chronically in some sensorimotor and subcortically connected regions. Exploratory global network analysis showed changes in network parameters indicative of possible acutely increased random connectivity and temporary reductions in modularity that were matched by local increases in connectedness and increased efficiency among more weakly connected regions. The global network parameters: shortest path-length, clustering coefficient and modularity that were most affected by trauma also scaled with the severity of injury, so that the corresponding regional measures were correlated to the injury severity most notably at 7 and 14 days and especially within, but not limited to, the contralateral cortex. These changes in functional network parameters are discussed in relation to the known time-course of physiologic and anatomic data that underlie structural and functional reorganization in this experiment model of TBI. PMID:26730520

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.

Clinical and imaging assessment of acute combat mild traumatic brain injury in Afghanistan

PubMed Central

Mac Donald, Christine L.; Rivet, Dennis; Ritter, John; May, Todd; Barefield, Maria; Duckworth, Josh; LaBarge, Donald; Asher, Dean; Drinkwine, Benjamin; Woods, Yvette; Connor, Michael; Brody, David L.

2015-01-01

Objective: To evaluate whether diffusion tensor imaging (DTI) will noninvasively reveal white matter changes not present on conventional MRI in acute blast-related mild traumatic brain injury (mTBI) and to determine correlations with clinical measures and recovery. Methods: Prospective observational study of 95 US military service members with mTBI enrolled within 7 days from injury in Afghanistan and 101 healthy controls. Assessments included Rivermead Post-Concussion Symptoms Questionnaire (RPCSQ), Post-Traumatic Stress Disorder Checklist Military (PCLM), Beck Depression Inventory (BDI), Balance Error Scoring System (BESS), Automated Neuropsychological Assessment Metrics (ANAM), conventional MRI, and DTI. Results: Significantly greater impairment was observed in participants with mTBI vs controls: RPCSQ (19.7 ± 12.9 vs 3.6 ± 7.1, p < 0.001), PCLM (32 ± 13.2 vs 20.9 ± 7.1, p < 0.001), BDI (7.4 ± 6.8 vs 2.5 ± 4.9, p < 0.001), and BESS (18.2 ± 8.4 vs 15.1 ± 8.3, p = 0.01). The largest effect size in ANAM performance decline was in simple reaction time (mTBI 74.5 ± 148.4 vs control −11 ± 46.6 milliseconds, p < 0.001). Fractional anisotropy was significantly reduced in mTBI compared with controls in the right superior longitudinal fasciculus (0.393 ± 0.022 vs 0.405 ± 0.023, p < 0.001). No abnormalities were detected with conventional MRI. Time to return to duty correlated with RPCSQ (r = 0.53, p < 0.001), ANAM simple reaction time decline (r = 0.49, p < 0.0001), PCLM (r = 0.47, p < 0.0001), and BDI (r = 0.36 p = 0.0005). Conclusions: Somatic, behavioral, and cognitive symptoms and performance deficits are substantially elevated in acute blast-related mTBI. Postconcussive symptoms and performance on measures of posttraumatic stress disorder, depression, and neurocognitive performance at initial presentation correlate with return-to-duty time. Although changes in fractional anisotropy are uncommon and subtle, DTI is more sensitive than conventional MRI in

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

Factors Associated with Long-Term Risk of Relapse after Unrelated Cord Blood Transplantation in Children with Acute Lymphoblastic Leukemia in Remission.

PubMed

Page, Kristin M; Labopin, Myriam; Ruggeri, Annalisa; Michel, Gerard; Diaz de Heredia, Cristina; O'Brien, Tracey; Picardi, Alessandra; Ayas, Mouhab; Bittencourt, Henrique; Vora, Ajay J; Troy, Jesse; Bonfim, Carmen; Volt, Fernanda; Gluckman, Eliane; Bader, Peter; Kurtzberg, Joanne; Rocha, Vanderson

2017-08-01

For pediatric patients with acute lymphoblastic leukemia (ALL), relapse is an important cause of treatment failure after unrelated cord blood transplant (UCBT). Compared with other donor sources, relapse is similar or even reduced after UCBT despite less graft-versus-host disease (GVHD). We performed a retrospective analysis to identify risk factors associated with the 5-year cumulative incidence of relapse after UCBT. In this retrospective, registry-based study, we examined the outcomes of 640 children (<18 years) with ALL in first complete remission (CR1; n = 257, 40%) or second complete remission (CR2; n = 383, 60%) who received myeloablative conditioning followed by a single-unit UCBT from 2000 to 2012. Most received antithymocyte globulin (88%) or total body irradiation (TBI; 69%), and cord blood grafts were primarily mismatched at 1 (50%) or 2 + (34%) HLA loci. Considering patients in CR1, the rates of 5-year overall survival (OS), leukemia-free survival (LFS), and relapse were 59%, 52%, and 23%, respectively. In multivariate analysis (MVA), acute GVHD (grades II to IV) and TBI protected against relapse. In patients in CR2, rates of 5-year OS, LFS, and the cumulative incidence of relapse were 46%, 44%, and 28%, respectively. In MVA, longer duration from diagnosis to UCBT (≥30 months) and TBI were associated with decreased relapse risk. Importantly, receiving a fully HLA matched graft was a strong risk factor for increased relapse in MVA. An exploratory analysis of all 640 patients supported the important association between the presence of acute GVHD and less relapse but also demonstrated an increased risk of nonrelapse mortality. In conclusion, the impact of GVHD as a graft-versus-leukemia marker is evident in pediatric ALL after UCBT. Strategies that promote graft-versus-leukemia while harnessing GVHD should be further investigated. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights

Recovered neuronal viability revealed by Iodine-123-iomazenil SPECT following traumatic brain injury.

PubMed

Koizumi, Hiroyasu; Fujisawa, Hirosuke; Kurokawa, Tetsu; Suehiro, Eiichi; Iwanaga, Hideyuki; Nakagawara, Jyoji; Suzuki, Michiyasu

2010-10-01

We evaluated cortical damages following traumatic brain injury (TBI) in the acute phase with [(123)I] iomazenil (IMZ) single photon emission computed tomography (SPECT). In all, 12 patients with cerebral contusion following TBI were recruited. All patients underwent IMZ SPECT within 1 week after TBI. To investigate the changes in distribution of IMZ in the cortex in the chronic phase, after conventional treatment, patients underwent IMZ SPECT again. A decrease in the accumulation of radioligand for the central benzodiazepine receptor in the cortex corresponding to the contusion revealed with computed tomography (CT) scans and magnetic resonance imaging (MRI) were shown on IMZ SPECT in the acute phase in all patients. In 9 of 12 patients (75%), images of IMZ SPECT obtained in the chronic phase of TBI showed that areas with a decreased distribution of IMZ were remarkably reduced in comparison with those obtained in the acute phase. Both CT scans and MRI showed a normal appearance of the cortex morphologically, where the binding potential of IMZ recovered in the chronic phase. Reduced binding potential of radioligand for the central benzodiazepine receptor is considered to be an irreversible reaction; however, in this study, IMZ accumulation in the cortex following TBI was recovered in the chronic phase in several patients. [(123)I] iomazenil SPECT may have a potential to disclose a reversible vulnerability of neurons following TBI.

Recovered neuronal viability revealed by Iodine-123-iomazenil SPECT following traumatic brain injury

PubMed Central

Koizumi, Hiroyasu; Fujisawa, Hirosuke; Kurokawa, Tetsu; Suehiro, Eiichi; Iwanaga, Hideyuki; Nakagawara, Jyoji; Suzuki, Michiyasu

2010-01-01

We evaluated cortical damages following traumatic brain injury (TBI) in the acute phase with [123I] iomazenil (IMZ) single photon emission computed tomography (SPECT). In all, 12 patients with cerebral contusion following TBI were recruited. All patients underwent IMZ SPECT within 1 week after TBI. To investigate the changes in distribution of IMZ in the cortex in the chronic phase, after conventional treatment, patients underwent IMZ SPECT again. A decrease in the accumulation of radioligand for the central benzodiazepine receptor in the cortex corresponding to the contusion revealed with computed tomography (CT) scans and magnetic resonance imaging (MRI) were shown on IMZ SPECT in the acute phase in all patients. In 9 of 12 patients (75%), images of IMZ SPECT obtained in the chronic phase of TBI showed that areas with a decreased distribution of IMZ were remarkably reduced in comparison with those obtained in the acute phase. Both CT scans and MRI showed a normal appearance of the cortex morphologically, where the binding potential of IMZ recovered in the chronic phase. Reduced binding potential of radioligand for the central benzodiazepine receptor is considered to be an irreversible reaction; however, in this study, IMZ accumulation in the cortex following TBI was recovered in the chronic phase in several patients. [123I] iomazenil SPECT may have a potential to disclose a reversible vulnerability of neurons following TBI. PMID:20683454

Focused and divided attention abilities in the acute phase of recovery from moderate to severe traumatic brain injury.

PubMed

Robertson, Kayela; Schmitter-Edgecombe, Maureen

2017-01-01

Impairments in attention following traumatic brain injury (TBI) can significantly impact recovery and rehabilitation effectiveness. This study investigated the multi-faceted construct of selective attention following TBI, highlighting the differences on visual nonsearch (focused attention) and search (divided attention) tasks. Participants were 30 individuals with moderate to severe TBI who were tested acutely (i.e. following emergence from PTA) and 30 age- and education-matched controls. Participants were presented with visual displays that contained either two or eight items. In the focused attention, nonsearch condition, the location of the target (if present) was cued with a peripheral arrow prior to presentation of the visual displays. In the divided attention, search condition, no spatial cue was provided prior to presentation of the visual displays. The results revealed intact focused, nonsearch, attention abilities in the acute phase of TBI recovery. In contrast, when no spatial cue was provided (divided attention condition), participants with TBI demonstrated slower visual search compared to the control group. The results of this study suggest that capitalizing on intact focused attention abilities by allocating attention during cognitively demanding tasks may help to reduce mental workload and improve rehabilitation effectiveness.

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

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

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.

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.

Development and psychometric properties of the Patient-Head Injury Participation Scale (P-HIPS) and the Patient-Head Injury Neurobehavioral Assessment Scale (P-HINAS): patient and family determined outcomes scales.

PubMed

Deb, Shoumitro; Bryant, Eleanor; Morris, Paul G; Prior, Lindsay; Lewis, Glyn; Haque, Sayeed

2007-06-01

To develop a measure to assess post-acute outcome following from traumatic brain injury (TBI) with particular emphasis on the emotional and the behavioral outcome. The second objective was to assess the test-retest reliability, internal consistency, and factor structure of the newly developed patient version of the Head Injury Participation Scale (P-HIPS) and Patient-Head Injury Neurobehavioral Scale (P-HINAS). Thirty-two TBI individuals and 27 carers took part in in-depth qualitative interviews exploring the consequences of the TBI. Interview transcripts were analyzed and key themes and concepts were used to construct the 49-item P-HIPS. A postal survey was then conducted on a cohort of 113 TBI patients to 'field test' the P-HIPS and the P-HINAS. All individual 49 items of the P-HIPS and their total score showed good test-retest reliability (0.93) and internal consistency (0.95). The P-HIPS showed a very good correlations with the Mayo Portland Adaptability Inventory-3 (MPAI-3) (0.87) and a moderate negative correlation with the Glasgow Outcome Scale-Extended (GOSE) (-0.51). Factor analysis extracted the following domains: 'Emotion/Behavior,' 'Independence/Community Living,' 'Cognition' and 'Physical'. The 'Emotion/Behavior' factor constituted the P-HINAS, which showed good internal consistency (0.93), test-retest reliability (0.91) and concurrent validity with MPAI subscale (0.82). Both the P-HIPS and the P-HINAS show strong psychometric properties. The qualitative methodology employed in the construction stage of the questionnaires provided good evidence of face and content validity.

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.

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.

Circulating MicroRNAs as Potential Biomarkers for Traumatic Brain Injury-Induced Hypopituitarism.

PubMed

Taheri, Serpil; Tanriverdi, Fatih; Zararsiz, Gokmen; Elbuken, Gulsah; Ulutabanca, Halil; Karaca, Zuleyha; Selcuklu, Ahmet; Unluhizarci, Kursad; Tanriverdi, Kahraman; Kelestimur, Fahrettin

2016-10-15

Traumatic brain injury (TBI), a worldwide public health problem, has recently been recognized as a common cause of pituitary dysfunction. Circulating microRNAs (miRNAs) present in the sera are characteristically altered in many pathological conditions and have been used as diagnostic markers for specific diseases. It is with this goal that we planned to study miRNA expression in patients with TBI-induced hypopituitarism. Thirty-eight patients (27 male, 11 female; mean age, 43 ± 18 years) who had been admitted to the neurosurgery intensive care unit due to TBI were included in the acute phase of the study. In the chronic phase, miRNA expression profile blood samples were drawn from 25 patients who had suffered TBI 5 years ago. In the acute phase (on Days 1, 7, and 28), a substantial amount of patients (26%, 40%, and 53%; respectively) had hypopituitarism (acute adrenocorticotropic hormone deficiency). In the chronic phase eight of 25 patients (32%) had TBI-induced-hypopituitarism. Forty-seven age-gender-similar healthy controls (25 male, 22 female, mean age: 41 ± 14 years) were included in the study. In order to identify potential candidate miRNA/miRNAs whose levels had been altered in response to TBI-induced hypopituitarism, 740 miRNA expression analyses were performed in the sera of TBI patients by high throughput real-time polymerase chain reaction. Statistical analyses showed that miRNA-126-3p (miR-126-3p) and miRNA-3610 (miR-3610) were detected in the sera of patients who developed hypopituitarism on the 1st, 7th, and 28th days, and in the 5th year following TBI. In addition, miRNA-3907 showed statistically significant and constant dynamic changes on the 1st, 7th, and 28th days, and in the 5th year in the patients with TBI. Our results indicated that altered expression of miR-126-3p and miR-3610 may play an important role in the development of TBI-induced hypopituitarism.

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.

Measurement and comparison of skin dose using OneDose MOSFET and Mobile MOSFET for patients with acute lymphoblastic leukemia.

PubMed

Mattar, Essam H; Hammad, Lina F; Al-Mohammed, Huda I

2011-07-01

Total body irradiation is a protocol used to treat acute lymphoblastic leukemia in patients prior to bone marrow transplant. It is involved in the treatment of the whole body using a large radiation field with extended source-skin distance. Therefore measuring and monitoring the skin dose during the treatment is important. Two kinds of metal oxide semiconductor field effect transistor (OneDose MOSFET and mobile MOSEFT) dosimeter are used during the treatment delivery to measure the skin dose to specific points and compare it with the target prescribed dose. The objective of this study was to compare the variation of skin dose in patients with acute lymphatic leukemia (ALL) treated with total body irradiation (TBI) using OneDose MOSFET detectors and Mobile MOSFET, and then compare both results with the target prescribed dose. The measurements involved 32 patient's (16 males, 16 females), aged between 14-30 years, with an average age of 22.41 years. One-Dose MOSFET and Mobile MOSFET dosimetry were performed at 10 different anatomical sites on every patient. The results showed there was no variation between skin dose measured with OneDose MOSFET and Mobile MOSFET in all patients. Furthermore, the results showed for every anatomical site selected there was no significant difference in the dose delivered using either OneDose MOSFET detector or Mobile MOSFET as compared to the prescribed dose. The study concludes that One-Dose MOSFET detectors and Mobile MOSFET both give a direct read-out immediately after the treatment; therefore both detectors are suitable options when measuring skin dose for total body irradiation treatment.

Application of ERPs neuromarkers for assessment and treatment of a patient with chronic crossed aphasia after severe TBI and long-term coma - Case Report.

PubMed

Chantsoulis, Marzena; Półrola, Paweł; Góral-Półrola, Jolanta; Hajdukiewicz, Anna; Supiński, Jan; Kropotov, Juri D; Pachalska, Maria

2017-03-31

 Objective. The study aimed to evaluate the application of ERPs neuromarkers for the assessment and treatment of a patient with chronic crossed aphasia after severe TBI and a long-term coma. An ambidextrous female patient, aged 29, suffered from posttraumatic chronic crossed aphasia, severe TBI and a prolonged coma after a car accident. The patient took part in two differentiated rehabilitation programmes of neurotherapy included 20 sessions of relative beta training and 20 sessions of rTMS; both programmes were combined with behavioural training. The patient was tested 3 times: before the experiment, after completion of programme A, and after completion of programme B. In the 1st recording, the neuromarker of aphasia was found - an excess of the P2 wave over the left temporal area. There was a cognitive control deficit - an excess of omission errors and an increase of RT variability - all indexes of sporadic ADHD. In the 2nd recording, slight improvements in cognitive control, and language functions were found. In the 3rd recording, after the rTMS sessions most of her cognitive dysfunctions had been resolved, including language functions. It should be stressed that the activation (especially the increase in the ERP potential of the right side over the frontal lobe) was found. The neuromarker of aphasia did not change, only the location had slightly moved frontally. The application of ERP neuromarkers assists in the diagnosis, treatment, and academic success of an ambidextrous patient with chronic posttraumatic aphasia and sporadic ADHD. ERPs can be used to assess the functional brain changes induced by neurotherapeutical programmes.

Successful pregnancy after total body irradiation and bone marrow transplantation for acute leukaemia.

PubMed

Giri, N; Vowels, M R; Barr, A L; Mameghan, H

1992-07-01

We report successful pregnancies in two young women (aged 24 and 20 years) following allogeneic bone marrow transplantation (BMT) for acute non-lymphoblastic leukaemia. Conditioning therapy consisted of cyclophosphamide (120 mg/kg) and total body irradiation (TBI, 12 Gy) in 2 Gy fractions once daily for 6 days or twice daily for 3 days. Graft-versus-host disease prophylaxis was with methotrexate alone. Both women were amenorrhoeic after BMT and gonadal testing indicated hypergonadotrophic hypogonadism. Both women had normal pregnancies (2 years and 5 years after BMT) resulting in normal healthy infants. Previously successful pregnancy has been reported after TBI in three women in whom the TBI dose was less than 8 Gy. Our cases illustrate that normal outcome of pregnancy is possible at even higher doses of TBI.

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.

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.

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

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

predicted by the structural deficits, not only within the primary sensorimotor injury site and pericontused regions, but the normally connected homotopic cortex, as well as subcortical regions, all of which persisted chronically. Especially novel in this study is the unanticipated finding of widespread increases in connection strength that dwarf both the degree and extent of the functional disconnections, and which persist chronically in some sensorimotor and subcortically connected regions. Exploratory global network analysis showed changes in network parameters indicative of possible acutely increased random connectivity and temporary reductions in modularity that were matched by local increases in connectedness and increased efficiency among more weakly connected regions. The global network parameters: shortest path-length, clustering coefficient and modularity that were most affected by trauma also scaled with the severity of injury, so that the corresponding regional measures were correlated to the injury severity most notably at 7 and 14 days and especially within, but not limited to, the contralateral cortex. These changes in functional network parameters are discussed in relation to the known time-course of physiologic and anatomic data that underlie structural and functional reorganization in this experiment model of TBI. Copyright © 2015 Elsevier Inc. All rights reserved.

Recent neuroimaging techniques in mild traumatic brain injury.

PubMed

Belanger, Heather G; Vanderploeg, Rodney D; Curtiss, Glenn; Warden, Deborah L

2007-01-01

Mild traumatic brain injury (TBI) is characterized by acute physiological changes that result in at least some acute cognitive difficulties and typically resolve by 3 months postinjury. Because the majority of mild TBI patients have normal structural magnetic resonance imaging (MRI)/computed tomography (CT) scans, there is increasing attention directed at finding objective physiological correlates of persistent cognitive and neuropsychiatric symptoms through experimental neuroimaging techniques. The authors review studies utilizing these techniques in patients with mild TBI; these techniques may provide more sensitive assessment of structural and functional abnormalities following mild TBI. Particular promise is evident with fMRI, PET, and SPECT scanning, as demonstrated by associations between brain activation and clinical outcomes.

Recovery of White Matter following Pediatric Traumatic Brain Injury Depends on Injury Severity.

PubMed

Genc, Sila; Anderson, Vicki; Ryan, Nicholas P; Malpas, Charles B; Catroppa, Cathy; Beauchamp, Miriam H; Silk, Timothy J

2017-02-15

Previous studies in pediatric traumatic brain injury (TBI) have been variable in describing the effects of injury severity on white-matter development. The present study used diffusion tensor imaging to investigate prospective sub-acute and longitudinal relationships between early clinical indicators of injury severity, diffusion metrics, and neuropsychological outcomes. Pediatric patients with TBI underwent magnetic resonance imaging (MRI) (n = 78, mean [M] = 10.56, standard deviation [SD] = 2.21 years) at the sub-acute stage after injury (M = 5.55, SD = 3.05 weeks), and typically developing children were also included and imaged (n = 30, M = 10.60, SD = 2.88 years). A sub-set of the patients with TBI (n = 15) was followed up with MRI 2 years post-injury. Diffusion MRI images were acquired at sub-acute and 2-year follow-up time points and analyzed using Tract-Based Spatial Statistics. At the sub-acute stage, mean diffusivity and axial diffusivity were significantly higher in the TBI group compared with matched controls (p < 0.05). TBI severity significantly predicted diffusion profiles at the sub-acute and 2-year post-injury MRI. Patients with more severe TBI also exhibited poorer information processing speed at 6-months post-injury, which in turn correlated with their diffusion metrics. These findings highlight that the severity of the injury not only has an impact on white-matter microstructure, it also impacts its recovery over time. Moreover, findings suggest that sub-acute microstructural changes may represent a useful prognostic marker to identify children at elevated risk for longer term deficits.

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.

[Fenspiride in patients with acute bronchitis].

PubMed

Płusa, Tadeusz; Ochwat, Agnieszka

2005-07-01

Fenspiride is an anti-inflammatory drug that may have a role in inhibition of histamine receptor H1 and influence a production of archidonic acid metabolites. The efficacy and tolerance of fenspiride therapy have been performed in patients with acute bronchitis. 597 patients, 51% females and 49% males, aged 39+/-18 years, were observed because of acute bronchitis. Fenspiride (Eurespal, Servier) was given in a dose of 240 mg per day (80 mg three times daily) for 14 consecutive days. During two following medical examinations - after 7 and 14 days of treatment, clinical symptoms of disease, therapy efficacy and tolerance were determined. Mean duration of acute bronchitis before fenspiride therapy was 2.3+/-1.3 days. In most of the patients (72%) a moderate, and in 27% mild degree of disease was diagnosed. Only 1% of patients were diagnosed as severe. Total evaluation of fenspiride efficacy in examined patients with acute bronchitis showed complete relief of symptoms after 7 days of therapy in 24% and after 14 days in 87% of patients. In 6% of patients after 7 days and in 1% after 14 days of fenspiride therapy no improvement was obtained. 28 adverse reactions were determined in 26 patients (4.3%): vertigo in 7, nausea in 6, somnolence in 5, palpitations in 4, fatigue in 2, abdominal pain in 2 and other symptoms in 2 patients. In 8 patients the therapy was discontinued after 7 days because of adverse reactions. In performed observations in patients with acute bronchitis the high clinical efficacy of fenspiride therapy. In 12% of patients an antibiotic support was necessary to obtain relief of the symptoms. Very good tolerance of the 14 days therapy was determined and it is recommended for safe clinical application.

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.

How healthcare provider talk with parents of children following severe traumatic brain injury is perceived in early acute care.

PubMed

Roscigno, Cecelia I; Savage, Teresa A; Grant, Gerald; Philipsen, Gerry

2013-08-01

Healthcare provider talk with parents in early acute care following children's severe traumatic brain injury (TBI) affects parents' orientations to these locales, but this connection has been minimally studied. This lack of attention to this topic in previous research may reflect providers' and researchers' views that these locales are generally neutral or supportive to parents' subsequent needs. This secondary analysis used data from a larger descriptive phenomenological study (2005-2007) with parents of children following moderate to severe TBI recruited from across the United States. Parents of children with severe TBI consistently had strong negative responses to the early acute care talk processes they experienced with providers, while parents of children with moderate TBI did not. Transcript data were independently coded using discourse analysis in the framework of ethnography of speaking. The purpose was to understand the linguistic and paralinguistic talk factors parents used in their meta-communications that could give a preliminary understanding of their cultural expectations for early acute care talk in these settings. Final participants included 27 parents of children with severe TBI from 23 families. We found the human constructed talk factors that parents reacted to were: a) access to the child, which is where information was; b) regular discussions with key personnel; c) updated information that is explained; d) differing expectations for talk in this context; and, e) perceived parental involvement in decisions. We found that the organization and nature of providers' talk with parents was perceived by parents to positively or negatively shape their early acute care identities in these locales, which influenced how they viewed these locales as places that either supported them and decreased their workload or discounted them and increased their workload for getting what they needed. Copyright © 2013 Elsevier Ltd. All rights reserved.

How Healthcare Provider Talk with Parents of Children Following Severe Traumatic Brain Injury is Perceived in Early Acute Care

PubMed Central

Savage, Teresa A.; Grant, Gerald; Philipsen, Gerry

2013-01-01

Healthcare provider talk with parents in early acute care following children’s severe traumatic brain injury (TBI) affects parents’ orientations to these locales, but this connection has been minimally studied. This lack of attention to this topic in previous research may reflect providers’ and researchers’ views that these locales are generally neutral or supportive to parents’ subsequent needs. This secondary analysis used data from a larger descriptive phenomenological study (2005 – 2007) with parents of children following moderate to severe TBI recruited from across the United States. Parents of children with severe TBI consistently had strong negative responses to the early acute care talk processes they experienced with providers, while parents of children with moderate TBI did not. Transcript data were independently coded using discourse analysis in the framework of ethnography of speaking. The purpose was to understand the linguistic and paralinguistic talk factors parents used in their meta-communications that could give a preliminary understanding of their cultural expectations for early acute care talk in these settings. Final participants included 27 parents of children with severe TBI from 23 families. We found the human constructed talk factors that parents reacted to were: a) access to the child, which is where information was; b) regular discussions with key personnel; c) updated information that is explained; d) differing expectations for talk in this context; and, e) perceived parental involvement in decisions. We found that the organization and nature of providers’ talk with parents was perceived by parents to positively or negatively shape their early acute care identities in these locales, which influenced how they viewed these locales as places that either supported them and decreased their workload or discounted them and increased their workload for getting what they needed. PMID:23746606

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

Acute computed tomography findings in patients with acute confusion of non-traumatic aetiology.

PubMed

West, W M; Ali, A; West, K P; Stultz, R

2011-10-01

A retrospective review was undertaken of all patients referred for computed tomography (CT) scans of the head for acute onset of confusion, not consequent on head trauma, during the period June 1, 2004 to May 31, 2007. Data were obtained by Microsoft Word search of the reports of the Radiology Department of the University Hospital of the West Indies, Kingston, Jamaica. Two hundred and twenty-one patients were reviewed: 103 men and 118 women. The mean age of the sample was 64 years; 168 patients (76%) were 50 years old or older. Computed tomography scans were reported normal in 170 (76.9%) patients; 45 patients (20.4%) had definite acute intracranial CT findings. Findings were equivocal in three patients (1.4%) and unavailable for three (1.4%); 23.2% and 15.6% of patients above and below the age of 50 years respectively showed acute abnormalities on CT The most common acute finding on CT scan was an ischaemic infarct (68%). Other abnormalities included intracerebral haemorrhage and metastases 6.2% each, toxoplasmosis and primary brain tumour 4.2% each and subdural haematoma and meningitis 2.1% each. The diagnoses of toxoplasmosis were made based on appearances typical of toxoplasmosis on CT scans in patients whose request stated that they were HIV positive. In the sample reviewed, most patients who presented with acute confusion were above the age of 50 years. Overall, 20.4% of patients from all age groups had acute abnormalities on CT with a relative higher proportion, 23.2% versus 15.6% of those over 50 years, having acute pathology. The most common abnormality was an ischaemic infarct. This finding is similar to that in developed countries and unlike that seen in other developing countries where infectious aetiologies predominate.

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

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

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.

The Australian National Sub-Acute and Non-Acute Patient casemix classification.

PubMed

Eagar, K

1999-01-01

The Australian National Sub-Acute and Non-Acute Patient (AN-SNAP) Version 1 casemix classification was completed in 1997. AN-SNAP is designed for the classification of sub-acute and non-acute care provided in both inpatient and ambulatory settings and is intended to be useful for both funding and clinical management purposes. The National Sub-Acute and Non-Acute Casemix Classification study has produced the first version of a national classification of sub-acute and non-acute care. Ongoing refinement (leading to Version 2) will be possible through further analysis of the existing data set in combination with analysis of the results of a carefully planned and phased implementation.

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

Acute Cholecystitis in Patients with Scrub Typhus.

PubMed

Lee, Hyun; Ji, Misuk; Hwang, Jeong-Hwan; Lee, Ja-Yeon; Lee, Ju-Hyung; Chung, Kyung Min; Lee, Chang-Seop

2015-11-01

Acute cholecystitis is a rare complication of scrub typhus. Although a few such cases have been reported in patients with scrub typhus, the clinical course is not well described. Of 12 patients, acute cholecystitis developed in 66.7% (8/12) of patients older than 60 yr. The scrub typhus group with acute cholecystitis had marginal significant longer hospital stay and higher cost than the group without cholecystitis according to propensity score matching. Scrub typhus should be kept in mind as a rare etiology of acute cholecystitis in endemic areas because the typical signs of scrub typhus such as skin rash and eschar can present after the abdominal pain.

Development and psychometric properties of the Patient-Head Injury Participation Scale (P-HIPS) and the Patient-Head Injury Neurobehavioral Assessment Scale (P-HINAS): patient and family determined outcomes scales

PubMed Central

Deb, Shoumitro; Bryant, Eleanor; Morris, Paul G; Prior, Lindsay; Lewis, Glyn; Haque, Sayeed

2007-01-01

Objective To develop a measure to assess post-acute outcome following from traumatic brain injury (TBI) with particular emphasis on the emotional and the behavioral outcome. The second objective was to assess the test–retest reliability, internal consistency, and factor structure of the newly developed patient version of the Head Injury Participation Scale (P-HIPS) and Patient-Head Injury Neurobehavioral Scale (P-HINAS). Method Thirty-two TBI individuals and 27 carers took part in in-depth qualitative interviews exploring the consequences of the TBI. Interview transcripts were analyzed and key themes and concepts were used to construct the 49-item P-HIPS. A postal survey was then conducted on a cohort of 113 TBI patients to ‘field test’ the P-HIPS and the P-HINAS. Results All individual 49 items of the P-HIPS and their total score showed good test–retest reliability (0.93) and internal consistency (0.95). The P-HIPS showed a very good correlations with the Mayo Portland Adaptability Inventory-3 (MPAI-3) (0.87) and a moderate negative correlation with the Glasgow Outcome Scale-Extended (GOSE) (−0.51). Factor analysis extracted the following domains: ‘Emotion/Behavior,’ ‘Independence/Community Living,’ ‘Cognition’ and ‘Physical’. The ‘Emotion/Behavior’ factor constituted the P-HINAS, which showed good internal consistency (0.93), test–retest reliability (0.91) and concurrent validity with MPAI subscale (0.82). Conclusions Both the P-HIPS and the P-HINAS show strong psychometric properties. The qualitative methodology employed in the construction stage of the questionnaires provided good evidence of face and content validity. PMID:19300568

Institutional Variation in Traumatic Brain Injury Acute Rehabilitation Practice.

PubMed

Seel, Ronald T; Barrett, Ryan S; Beaulieu, Cynthia L; Ryser, David K; Hammond, Flora M; Cullen, Nora; Garmoe, William; Sommerfeld, Teri; Corrigan, John D; Horn, Susan D

2015-08-01

To describe institutional variation in traumatic brain injury (TBI) inpatient rehabilitation program characteristics and evaluate to what extent patient factors and center effects explain how TBI inpatient rehabilitation services are delivered. Secondary analysis of a prospective, multicenter, cohort database. TBI inpatient rehabilitation programs. Patients with complicated mild, moderate, or severe TBI (N=2130). Not applicable. Mean minutes; number of treatment activities; use of groups in occupational therapy, physical therapy, speech therapy, therapeutic recreation, and psychology inpatient rehabilitation sessions; and weekly hours of treatment. A wide variation was observed between the 10 TBI programs, including census size, referral flow, payer mix, number of dedicated beds, clinician experience, and patient characteristics. At the centers with the longest weekday therapy sessions, the average session durations were 41.5 to 52.2 minutes. At centers with the shortest weekday sessions, the average session durations were approximately 30 minutes. The centers with the highest mean total weekday hours of occupational, physical, and speech therapies delivered twice as much therapy as the lowest center. Ordinary least-squares regression modeling found that center effects explained substantially more variance than patient factors for duration of therapy sessions, number of activities administered per session, use of group therapy, and amount of psychological services provided. This study provides preliminary evidence that there is significant institutional variation in rehabilitation practice and that center effects play a stronger role than patient factors in determining how TBI inpatient rehabilitation is delivered. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

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.

Whole body proton irradiation causes acute damage to bone marrow hematopoietic progenitor and stem cells in mice.

PubMed

Chang, Jianhui; Wang, Yingying; Pathak, Rupak; Sridharan, Vijayalakshmi; Jones, Tamako; Mao, Xiao Wen; Nelson, Gregory; Boerma, Marjan; Hauer-Jensen, Martin; Zhou, Daohong; Shao, Lijian

2017-12-01

Exposure to proton irradiation during missions in deep space can lead to bone marrow injury. The acute effects of proton irradiation on hematopoietic stem and progenitor cells remain undefined and thus were investigated. We exposed male C57BL/6 mice to 0.5 and 1.0 Gy proton total body irradiation (proton-TBI, 150 MeV) and examined changes in peripheral blood cells and bone marrow (BM) progenitors and LSK cells 2 weeks after exposure. 1.0 Gy proton-TBI significantly reduced the numbers of peripheral blood cells compared to 0.5 Gy proton-TBI and unirradiated animals, while the numbers of peripheral blood cell counts were comparable between 0.5 Gy proton-TBI and unirradiated mice. The frequencies and numbers of LSK cells and CMPs in BM of 0.5 and 1.0 Gy irradiated mice were decreased in comparison to those of normal controls. LSK cells and CMPs and their progeny exhibited a radiation-induced impairment in clonogenic function. Exposure to 1.0 Gy increased cellular apoptosis but not the production of reactive oxygen species (ROS) in CMPs two weeks after irradiation. LSK cells from irradiated mice exhibited an increase in ROS production and apoptosis. Exposure to proton-TBI can induce acute damage to BM progenitors and LSK cells.

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

Changes in sexual functioning from 6 to 12 months following traumatic brain injury: a prospective TBI model system multicenter study.

PubMed

Hanks, Robin A; Sander, Angelle M; Millis, Scott R; Hammond, Flora M; Maestas, Kacey L

2013-01-01

To investigate longitudinal changes in sexual functioning during the first year following moderate to severe traumatic brain injury (TBI). Prospective cohort study. Community. 182 persons (53 women and 129 men) with moderate to severe TBI who were admitted to 1 of 6 participating TBI Model System centers and followed in the community at 6 and 12 months after injury. Derogatis Interview for Sexual Functioning-Self-Report (DISF-SR); Global Sexual Satisfaction Index (GSSI). Mean T-scores on the DISF-SR Arousal subscale demonstrated marginal improvement over time, with a 2.59-point increase (P = .05) from 6 to 12 months after injury. There were no significant differences over this 6-month period on the remaining DISF-SR subscales, including sexual cognition/fantasy, sexual behavior/experience, and orgasm. There was no significant change in satisfaction with sexual functioning on the GSSI from 6 months (72% satisfied) to 12 months (71% satisfied). Sexual function and satisfaction appears to be stable in those with moderate to severe TBI from 6 to 12 months after injury, with the exception of minimal improvement in arousal. These findings, to our knowledge, reflect the first evidence regarding prospective changes in sexual functioning in this population. Future research can go far to assist clinicians in treatment planning and managing patient expectations of recovery of sexual functioning after TBI.

Antibiotic prophylaxia in patients with severe acute pancreatitis.

PubMed

Zhou, Yan-Ming; Xue, Zuo-Liang; Li, Yu-Min; Zhu, You-Quan; Cao, Nong

2005-02-01

The prophylactic use of antibiotics in patients with severe acute pancreatitis remains contentious. This study was undertaken to review the current studies on antibiotic prophylaxis in patients with severe acute pancreatitis. All papers found by a Medline search were relevant to human trials of antibiotic prophylaxis in patients with severe acute pancreatitis. In the 1970s, three small randomized studies of prophylactic ampicillin in the treatment of acute pancreatitis showed no effect on mortality or morbidity, but the inclusion of patients at low risk for infection and the use of an ineffective antibiotic were insufficient to detect any differences. From 1993 to 2001, eight prospective clinical trials of antibiotic prophylaxis were conducted in patients with severe acute pancreatitis (SAP). Seven of the 8 trials showed significant effect of the prophylaxis in prevention of pancreatic infections, and one showed significant improvement of clinical course documented by the Acute Physiology and Chronic Health Evaluation II (APACHE II) scores. Only two trials did demonstrate the significance of the prophylaxis in lowering the mortality rate. Despite variations in drug agents, study size and patient selection, duration of treatment, and methodology (None of the studies was double-blinded), a meta-analysis showed the positive effect of antibiotics in reducing the mortality. We suggested that antibiotic prophylaxis with proven efficacy in necrotic pancreatic tissues should be given to all patients with acute necrotizing pancreatitis. In recent years, however, the first double-blind, placebo-controlled multicenter study from Germany detected no benefit of antibiotic prophylaxis with respect to the risk of developing infected pancreatic necrosis. Prophylactic antibiotics for severe acute pancreatitis is still a matter of discussion and further studies are required to provide adequate data to answer many questions and to define the role of antibiotic prophylaxis in patients

Traumatic brain injury and post-acute decline: what role does environmental enrichment play? A scoping review

PubMed Central

Frasca, Diana; Tomaszczyk, Jennifer; McFadyen, Bradford J.; Green, Robin E.

2013-01-01

Objectives: While a growing number of studies provide evidence of neural and cognitive decline in traumatic brain injury (TBI) survivors during the post-acute stages of injury, there is limited research as of yet on environmental factors that may influence this decline. The purposes of this paper, therefore, are to (1) examine evidence that environmental enrichment (EE) can influence long-term outcome following TBI, and (2) examine the nature of post-acute environments, whether they vary in degree of EE, and what impact these variations have on outcomes. Methods: We conducted a scoping review to identify studies on EE in animals and humans, and post-discharge experiences that relate to barriers to recovery. Results: One hundred and twenty-three articles that met inclusion criteria demonstrated the benefits of EE on brain and behavior in healthy and brain-injured animals and humans. Nineteen papers on post-discharge experiences revealed that variables such as insurance coverage, financial, and social support, home therapy, and transition from hospital to home, can have an impact on clinical outcomes. Conclusion: There is evidence to suggest that lack of EE, whether from lack of resources or limited ability to engage in such environments, may play a role in post-acute cognitive and neural decline. Maximizing EE in the post-acute stages of TBI may improve long-term outcomes for the individual, their family and society. PMID:23616755

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

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.

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

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.

Laparoscopic Cholecystectomy for Acute Cholecystitis in Elderly Patients

PubMed Central

Filho, Euler de Medeiros Ázaro; Galvão, Thales Delmondes; Ettinger, João Eduardo Marques de Menezes; Silva Reis, Jadson Murilo; Lima, Marcos; Fahel, Edvaldo

2006-01-01

Background: Acute cholecystitis is the major complication of biliary lithiasis, for which laparoscopic treatment has been established as the standard therapy. With longer life expectancy, acute cholecystitis has often been seen in elderly patients (>65 years old) and is often accompanied by comorbity and severe complications. We sought to compare the outcome of laparoscopic treatment for acute cholecystitis with special focus on comparison between elderly and nonelderly patients. Method: This study was a prospective analysis of 190 patients who underwent laparoscopic cholecystectomy due to acute cholecystitis or chronic acute cholecystitis, comparing elderly and nonelderly patients. Results: Of 190 patients, 39 (21%) were elderly (>65 years old) and 151 (79%) were not elderly (≤65 years), with conversion rates of 10.3% and 6.6% (P=0.49), respectively. The incidence of postoperative complications in elderly and nonelderly patients were the following, respectively: atelectasis 5.1% and 2.0% (P=0.27); respiratory infection 5.1% and 2.7% (P=0.6); bile leakage 5.1% and 2.0% (P=0.27), and intraabdominal abscess 1 case (0.7%) and no incidence (P=1). Conclusion: According to our data, laparoscopic cholecystectomy is a safe and efficient procedure for the treatment of acute cholecystitis in patients older than 65 years of age. PMID:17575761

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.

Parent Perceptions of How Nurse Encounters Can Provide Caring Support for the Family in Early Acute Care Following Children’s Severe Traumatic Brain Injury

PubMed Central

Roscigno, Cecelia I.

2016-01-01

Objective A child’s severe traumatic brain injury (TBI) creates a family crisis requiring extensive cultural, informational, psychological, and environmental support. Nurses need to understand parents’ expectations of caring in early acute care so they can tailor their attitudes, beliefs, and behaviors appropriately to accommodate the family’s needs. Methods In a previous qualitative study of 42 parents or caregivers from 37 families of children with moderate to severe TBI, parents of children with severe TBI (n = 25) described their appraisals of nurse caring and uncaring behaviors in early acute care. Swanson’s theory of caring was used to categorize parents’ descriptions in order to inform nursing early acute care practices and family-centered care. Results Caring nurse encounters included: (a) involving parents in the care of their child and reflecting on all socio-cultural factors shaping family resources and responses (knowing); (b) respecting that family grief can be co-mingled with resilience, and that parents are typically competent to be involved in decision-making (maintaining belief); (d) actively listening and engaging parents in order to fully understand family values and needs (being with); (e) decreasing parents’ workload to get information, emotional support, and providing a safe cultural, psychological, and physical environment for the family (doing for), and; (f) providing anticipatory guidance to navigate the early acute care system and giving assistance to learn and adjust to their situation (enabling). Conclusion Application of Swanson’s caring theory is prescriptive in helping individual nurses and early acute care systems to meet important family needs following children’s severe TBI. PMID:26871242

Pharmacokinetic Behavior of Phenytoin in Head Trauma and Cerebrovascular Accident Patients in an Iranian Population.

PubMed

Alimardani, Shahnaz; Sadrai, Sima; Masoumi, Hamidreza Taghvaye; Salari, Pooneh; Najafi, Atabak; Eftekhar, Behzad; Mojtahedzadeh, Mojtaba

2017-01-01

Acute brain injury is one of the leading causes of morbidity and mortality worldwide. Phenytoin has been commonly used as an anticonvulsant agent for the treatment or prophylaxis of seizures following acute brain injury. After a severe head injury, several pharmacokinetic changes occur. The aim of this study is the comparative evaluation of phenytoin serum concentration in patients with traumatic and nontraumatic brain injury (TBI). This prospective observational study was performed on twenty adult brain injury patients who were admitted to an Intensive Care Unit and required phenytoin for the treatment or prophylaxis of postinjury seizures. For all the patients, phenytoin serum concentration was determined in three scheduled time points. Phenytoin serum concentration and pharmacokinetic parameters were compared between patients with TBI and cerebrovascular accident (CVA). The V max and K m were significantly higher in head trauma (HT) patients than the CVA group. The phenytoin concentration (C p ) and the C p /dose ratio were significantly higher in the CVA group patients during the first sampling ( P < 0.05). The Acute Physiology and Chronic Health Evaluation П (APACHE П) score was significantly lower than the baseline at the end of the study in each group of patients ( P < 0.05). In addition, no significant correlation was observed between V max , K m , C p , C p /dose ratio, and APACHE II scores at the time of sampling. Due to significant differences in phenytoin plasma concentration and pharmacokinetic parameters between HT and CVA patients, close attention must be paid to the pharmacokinetic behavior of phenytoin in the efforts to improve the patient's outcome after a severe HT.

Reciprocal Risk of Acute Kidney Injury and Acute Respiratory Distress Syndrome in Critically Ill Burn Patients.

PubMed

Clemens, Michael S; Stewart, Ian J; Sosnov, Jonathan A; Howard, Jeffrey T; Belenkiy, Slava M; Sine, Christy R; Henderson, Jonathan L; Buel, Allison R; Batchinsky, Andriy I; Cancio, Leopoldo C; Chung, Kevin K

2016-10-01

To evaluate the association between acute respiratory distress syndrome and acute kidney injury with respect to their contributions to mortality in critically ill patients. Retrospective analysis of consecutive adult burn patients requiring mechanical ventilation. A 16-bed burn ICU at tertiary military teaching hospital. Adult patients more than 18 years old requiring mechanical ventilation during their initial admission to our burn ICU from January 1, 2003, to December 31, 2011. None. A total 830 patients were included, of whom 48.2% had acute kidney injury (n = 400). These patients had a 73% increased risk of developing acute respiratory distress syndrome after controlling for age, gender, total body surface area burned, and inhalation injury (hazard ratio, 1.73; 95% CI, 1.18-2.54; p = 0.005). In a reciprocal multivariate analysis, acute respiratory distress syndrome (n = 299; 36%) demonstrated a strong trend toward developing acute kidney injury (hazard ratio, 1.39; 95% CI, 0.99-1.95; p = 0.05). There was a 24% overall in-hospital mortality (n = 198). After adjusting for the aforementioned confounders, both acute kidney injury (hazard ratio, 3.73; 95% CI, 2.39-5.82; p < 0.001) and acute respiratory distress syndrome (hazard ratio, 2.16; 95% CI, 1.58-2.94; p < 0.001) significantly contributed to mortality. Age, total body surface area burned, and inhalation injury were also significantly associated with increased mortality. Acute kidney injury increases the risk of acute respiratory distress syndrome in mechanically ventilated burn patients, whereas acute respiratory distress syndrome similarly demonstrates a strong trend toward the development of acute kidney injury. Acute kidney injury and acute respiratory distress syndrome are both independent risks for subsequent death. Future research should look at this interplay for possible early interventions.

Measurement and comparison of skin dose using OneDose MOSFET and Mobile MOSFET for patients with acute lymphoblastic leukemia

PubMed Central

Mattar, Essam H.; Hammad, Lina F.; Al-Mohammed, Huda I.

2011-01-01

Summary Background Total body irradiation is a protocol used to treat acute lymphoblastic leukemia in patients prior to bone marrow transplant. It is involved in the treatment of the whole body using a large radiation field with extended source-skin distance. Therefore measuring and monitoring the skin dose during the treatment is important. Two kinds of metal oxide semiconductor field effect transistor (OneDose MOSFET and mobile MOSEFT) dosimeter are used during the treatment delivery to measure the skin dose to specific points and compare it with the target prescribed dose. The objective of this study was to compare the variation of skin dose in patients with acute lymphatic leukemia (ALL) treated with total body irradiation (TBI) using OneDose MOSFET detectors and Mobile MOSFET, and then compare both results with the target prescribed dose. Material/Methods The measurements involved 32 patient’s (16 males, 16 females), aged between 14–30 years, with an average age of 22.41 years. One-Dose MOSFET and Mobile MOSFET dosimetry were performed at 10 different anatomical sites on every patient. Results The results showed there was no variation between skin dose measured with OneDose MOSFET and Mobile MOSFET in all patients. Furthermore, the results showed for every anatomical site selected there was no significant difference in the dose delivered using either OneDose MOSFET detector or Mobile MOSFET as compared to the prescribed dose. Conclusions The study concludes that One-Dose MOSFET detectors and Mobile MOSFET both give a direct read-out immediately after the treatment; therefore both detectors are suitable options when measuring skin dose for total body irradiation treatment. PMID:21709641

Antithrombotic agents intake prior to injury does not affect outcome after a traumatic brain injury in hospitalized elderly patients.

PubMed

Julien, Jessica; Alsideiri, Ghusn; Marcoux, Judith; Hasen, Mohammed; Correa, José A; Feyz, Mitra; Maleki, Mohammed; de Guise, Elaine

2017-04-01

The purpose of this study is to investigate the effect of risk factors including International Normalized Ratio (INR) as well as the Partial Thromboplastin Time (PTT) scores on several outcomes, including hospital length of stay (LOS) and The Extended Glasgow Outcome Scale (GOSE) following TBI in the elderly population. Data were retrospectively collected on patients (n=982) aged 65 and above who were admitted post TBI to the McGill University Health Centre-Montreal General Hospital from 2000 to 2011. Age, Injury Severity Score (ISS), Glasgow Coma Scale score (GCS), type of trauma (isolated TBI vs polytrauma including TBI), initial CT scan results according to the Marshall Classification and the INR and PTT scores and prescriptions of antiplatelet or anticoagulant agents (AP/AC) were collected. Results also indicated that age, ISS and GSC score have an effect on the GOSE score. We also found that taking AC/AP has an effect on GOSE outcome, but that this effects depends on PTT, with lower odds of a worse outcome for those taking AC/AP agents as the PTT value goes up. However, this effect only becomes significant as the PTT value reaches 60 and above. Age and injury severity rather than antithrombotic agent intake are associated with adverse acute outcome such as GOSE in hospitalized elderly TBI patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

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�

Noninvasive ventilation for patients with acute lung injury or acute respiratory distress syndrome.

PubMed

Nava, Stefano; Schreiber, Ania; Domenighetti, Guido

2011-10-01

Few studies have been performed on noninvasive ventilation (NIV) to treat hypoxic acute respiratory failure in patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). The outcomes of these patients, for whom endotracheal intubation is not mandatory, depend on the degree of hypoxia, the presence of comorbidities and complications, and their illness severity. The use of NIV as an alternative to invasive ventilation in severely hypoxemic patients with ARDS (ie, P(aO(2))/F(IO(2)) < 200) is not generally advisable and should be limited to hemodynamically stable patients who can be closely monitored in an intensive care unit by highly skilled staff. Early NIV application may be extremely helpful in immunocompromised patients with pulmonary infiltrates, in whom intubation dramatically increases the risk of infection, pneumonia, and death. The use of NIV in patients with severe acute respiratory syndrome and other airborne diseases has generated debate, despite encouraging clinical results, mainly because of safety issues. Overall, the high rate of NIV failure suggests a cautious approach to NIV use in patients with ALI/ARDS, including early initiation, intensive monitoring, and prompt intubation if signs of NIV failure emerge.

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

Hypothalamo-pituitary dysfunction in patients with chronic subdural hematoma.

PubMed

Hána, V; Kosák, M; Masopust, V; Netuka, D; Lacinová, Z; Kršek, M; Marek, J; Pecen, L

2012-01-01

Relatively frequent pituitary hormone deficiencies are observed after traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) and according to the published studies the neuroendocrine consequenses of traumatic brain injury are underdiagnosed. In a cohort of 59 patients (49 males, mean age 68.3 years, 36-88 years) after evacuation of subdural hematoma (SDH) were evaluated hypothalamo-pituitary functions one week after surgery, after three months and after one year. Hypogonadism was present in 26 % of patients in an acute phase, but in the majority had a transient character. Less than half of patients was GH deficient (GHD) according to the GHRH+arginine test. We did not find any serious case of hypocortisolism, hypothyroidism, diabetes insipidus centralis nor syndrome of inappropriate secretion of ADH (SIADH). Transient partial hypocortisolism was present in two cases, but resolved. We did not find relation between extension of SDH or clinical severity and development of hypopituitarism. In conclusion, in some patients with SDH growth hormone deficiency or hypogonadism was present. No serious hypocortisolism, hypothyroidism, diabetes insipidus nor SIADH was observed. The possibility of neuroendocrine dysfunction should be considered in patients with SDH, although the deficits are less frequent than in patients after TBI or SAH.

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.

Effect of Granulocyte Colony-Stimulating Factor-Combined Conditioning in Cord Blood Transplantation for Myelodysplastic Syndrome and Secondary Acute Myeloid Leukemia: A Retrospective Study in Japan.

PubMed

Konuma, Takaaki; Takahashi, Satoshi; Uchida, Naoyuki; Kuwatsuka, Yachiyo; Yamasaki, Satoshi; Aoki, Jun; Onishi, Yasushi; Aotsuka, Nobuyuki; Ohashi, Kazuteru; Mori, Takehiko; Masuko, Masayoshi; Nakamae, Hirohisa; Miyamura, Kouichi; Kato, Koji; Atsuta, Yoshiko; Kato, Seiko; Asano, Shigetaka; Takami, Akiyoshi; Miyazaki, Yasushi

2015-09-01

Granulocyte colony-stimulating factor (G-CSF) increases the susceptibility of dormant malignant or nonmalignant hematopoietic cells to cytarabine arabinoside (Ara-C) through the induction of cell cycle entry. Therefore, G-CSF-combined conditioning before allogeneic stem cell transplantation might positively contribute to decreased incidences of relapse and graft failure without having to increase the dose of cytotoxic drugs. We conducted a retrospective nationwide study of 336 adult patients with myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia (sAML) after single-unit cord blood transplantation (CBT) who underwent 4 different kinds of conditioning regimens: total body irradiation (TBI) ≥ 8 Gy + Ara-C/G-CSF + cyclophosphamide (CY) (n = 65), TBI ≥ 8 Gy + Ara-C + CY (n = 119), TBI ≥ 8 Gy + other (n = 104), or TBI < 8 Gy or non-TBI (n = 48). The TBI ≥ 8 Gy + Ara-C/G-CSF + CY regimen showed significantly higher incidence of neutrophil engraftment (hazard ratio, 1.52; 95% confidence interval [CI], 1.10 to 2.08; P = .009) and lower overall mortality (hazard ratio, .46; 95% CI, .26 to .82; P = .008) rates compared with those without a G-CSF regimen. This retrospective study shows that the G-CSF-combined conditioning regimen provides better engraftment and survival results in CBT for adults with MDS and sAML. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Predictors of sexual functioning and satisfaction 1 year following traumatic brain injury: a TBI model systems multicenter study.

PubMed

Sander, Angelle M; Maestas, Kacey Little; Nick, Todd G; Pappadis, Monique R; Hammond, Flora M; Hanks, Robin A; Ripley, David L

2013-01-01

To investigate predictors of sexual functioning 1 year following traumatic brain injury (TBI). Prospective cohort study. Community. A total of 255 persons with TBI (187 males; 68 females) who had been treated at 1 of 6 TBI Model Systems inpatient rehabilitation units and were living in the community. Derogatis Interview for Sexual Functioning-Self-Report (DISF-SR); Global Satisfaction With Sexual Functioning (Global Sexual Satisfaction Index); Participation Assessment With Recombined Tools-Objective; Patient Health Questionnaire-9. Older age, female gender, and more severe injury were associated with greater sexual dysfunction 1 year following injury. As age increased from 24 to 49 years, the odds of sexual impairment increased more than 3-fold (95% confidence interval: 1.82-5.88). Females had a 2.5 increase in odds of sexual impairment compared with males (95% confidence interval: 1.23-5.26). Greater social participation was predictive of better sexual functioning. Dissatisfaction with sexual functioning was predicted by older age and depression. Older persons and females appear to be at greater risk for sexual dysfunction after TBI and may benefit from specialized assessment and treatment services. Relationships were identified between social participation and sexual function and between depression and sexual satisfaction that may serve as clinical indicators for further assessment and intervention. Further research is needed to elucidate these relationships and identify effective clinical approaches.

Characteristics and prognosis of patients admitted to a hospital emergency department for traumatic brain injury and with anticoagulant or antiplatelet treatment.

PubMed

Yuguero, Oriol; Guzman, Marianela; Castañ, Teresa; Forné, Carles; Galindo, Gisela; Pujol, Jesus

2018-06-10

To determine mortality and complications of patients with traumatic brain injury (TBI) with antiplatelet or anticoagulant treatment in a hospital emergency department. Study of hospital cohorts of the 243 patients who attended with pure TBI to the emergency service of the Arnau de Vilanova University Hospital in Lleida between June 1, 2015 and June 1, 2016. Sociodemographic, clinical and other variables related to clinical management were collected. Presence of complications and in-hospital mortality were registered at 24hours, at 48hours and one week after TBI. Overall, 50.2% of patients were men, with median age of 80.8years, and without CT-scan findings at admission in 62.3% of cases. A total of 14 patients died (5.8%). Overall mortality was associated with comorbidity, with knowledge loss and with fluctuation of the Glasgow comma scale in the acute process. Patients treated with anticoagulants (39.5%) or antiplatelet agents (33.3%) were older, with higher degree of dependency and more comorbidity, but did not present more complications. Without reaching statistical significance, higher mortality was observed during the first week in anticoagulated patients (7.3% vs 4.8%, P=.585) or with antiplatelet treatment (8.6% vs 4.3%, P=.241) with respect to those not treated. No worse results have been observed in number of complications in patients with TBI treated with anticoagulant or antiplatelet treatment, so clinical management seems appropriate. The higher mortality could be explained by the greater complexity of these patients. It would be necessary to carry out more studies, preferably prospective with follow-up after discharge, in order to establish causal mechanisms between clinical management and mortality or associated complications to TBI. Copyright © 2018 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.

Volumetric analysis of day of injury computed tomography is associated with rehabilitation outcomes after traumatic brain injury.

PubMed

Majercik, Sarah; Bledsoe, Joseph; Ryser, David; Hopkins, Ramona O; Fair, Joseph E; Brock Frost, R; MacDonald, Joel; Barrett, Ryan; Horn, Susan; Pisani, David; Bigler, Erin D; Gardner, Scott; Stevens, Mark; Larson, Michael J

2017-01-01

Day-of-injury (DOI) brain lesion volumes in traumatic brain injury (TBI) patients are rarely used to predict long-term outcomes in the acute setting. The purpose of this study was to investigate the relationship between acute brain injury lesion volume and rehabilitation outcomes in patients with TBI at a level one trauma center. Patients with TBI who were admitted to our rehabilitation unit after the acute care trauma service from February 2009-July 2011 were eligible for the study. Demographic data and outcome variables including cognitive and motor Functional Independence Measure (FIM) scores, length of stay (LOS) in the rehabilitation unit, and ability to return to home were obtained. The DOI quantitative injury lesion volumes and degree of midline shift were obtained from DOI brain computed tomography scans. A multiple stepwise regression model including 13 independent variables was created. This model was used to predict postrehabilitation outcomes, including FIM scores and ability to return to home. A p value less than 0.05 was considered significant. Ninety-six patients were enrolled in the study. Mean age was 43 ± 21 years, admission Glasgow Coma Score was 8.4 ± 4.8, Injury Severity Score was 24.7 ± 9.9, and head Abbreviated Injury Scale score was 3.73 ± 0.97. Acute hospital LOS was 12.3 ± 8.9 days, and rehabilitation LOS was 15.9 ± 9.3 days. Day-of-injury TBI lesion volumes were inversely associated with cognitive FIM scores at rehabilitation admission (p = 0.004) and discharge (p = 0.004) and inversely associated with ability to be discharged to home after rehabilitation (p = 0.006). In a cohort of patients with moderate to severe TBI requiring a rehabilitation unit stay after the acute care hospital stay, DOI brain injury lesion volumes are associated with worse cognitive FIM scores at the time of rehabilitation admission and discharge. Smaller-injury volumes were associated with eventual discharge to home. Volumetric neuroimaging in the acute

Volumetric analysis of day of injury computed tomography is associated with rehabilitation outcomes after traumatic brain injury

PubMed Central

Majercik, Sarah; Bledsoe, Joseph; Ryser, David; Hopkins, Ramona O.; Fair, Joseph E.; Frost, R. Brock; MacDonald, Joel; Barrett, Ryan; Horn, Susan; Pisani, David; Bigler, Erin D.; Gardner, Scott; Stevens, Mark; Larson, Michael J.

2016-01-01

Introduction Day-of-injury (DOI) brain lesion volumes in traumatic brain injury (TBI) patients are rarely used to predict long-term outcomes in the acute setting. The purpose of this study was to investigate the relationship between acute brain injury lesion volume and rehabilitation outcomes in patients with TBI at a Level One Trauma Center. Methods Patients with TBI who were admitted to our rehabilitation unit after the acute care trauma service from February 2009-July 2011 were eligible for the study. Demographic data and outcome variables including cognitive and motor FIM scores, length of stay (LOS) in the rehabilitation unit, and ability to return to home were obtained. DOI quantitative injury lesion volumes and degree of midline shift were obtained from day-of-injury (DOI) brain computed tomography (CT) scans. A multiple step-wise regression model including 13 independent variables was created. This model was used to predict post-rehabilitation outcomes, including FIM scores and ability to return to home. P<0.05 was considered significant. Results 96 patients were enrolled in the study. Mean age was 43±21 years, admission Glasgow Coma Score 8.4±4.8, Injury Severity Score 24.7±9.9, and head Abbreviated Injury Scale score 3.73±0.97. Acute hospital length of stay (LOS) was 12.3±8.9 days and rehabilitation LOS was 15.9±9.3 days. Day-of-injury TBI lesion volumes were inversely associated with cognitive FIM scores at rehabilitation admission (p=0.004) and discharge (p=0.004) and inversely associated with ability to be discharged to home after rehabilitation (p=0.006). Conclusion In a cohort of patients with moderate to severe TBI requiring a rehabilitation unit stay after the acute care hospital stay, DOI brain injury lesion volumes are associated with worse cognitive FIM scores at the time of rehabilitation admission and discharge. Smaller injury volumes were associated with eventual discharge to home. Volumetric neuroimaging in the acute injury phase may

An exploratory study of the association of acute posttraumatic stress, depression, and pain to cognitive functioning in mild traumatic brain injury.

PubMed

Massey, Jessica S; Meares, Susanne; Batchelor, Jennifer; Bryant, Richard A

2015-07-01

Few studies have examined whether psychological distress and pain affect cognitive functioning in the acute to subacute phase (up to 30 days postinjury) following mild traumatic brain injury (mTBI). The current study explored whether acute posttraumatic stress, depression, and pain were associated with performance on a task of selective and sustained attention completed under conditions of increasing cognitive demands (standard, auditory distraction, and dual-task), and on tests of working memory, memory, processing speed, reaction time (RT), and verbal fluency. At a mean of 2.87 days (SD = 2.32) postinjury, 50 adult mTBI participants, consecutive admissions to a Level 1 trauma hospital, completed neuropsychological tests and self-report measures of acute posttraumatic stress, depression, and pain. A series of canonical correlation analyses was used to explore the relationships of a common set of psychological variables to various sets of neuropsychological variables. Significant results were found on the task of selective and sustained attention. Strong relationships were found between psychological variables and speed (r(c) = .56, p = .02) and psychological variables and accuracy (r(c) = .68, p = .002). Pain and acute posttraumatic stress were associated with higher speed scores (reflecting more correctly marked targets) under standard conditions. Acute posttraumatic stress was associated with lower accuracy scores across all task conditions. Moderate but nonsignificant associations were found between psychological variables and most cognitive tasks. Acute posttraumatic stress and pain show strong associations with selective and sustained attention following mTBI. (c) 2015 APA, all rights reserved).

Prevalence and Risk Factors for Early Seizure in Patients with Traumatic Brain Injury: Analysis from National Trauma Data Bank.

PubMed

Majidi, Shahram; Makke, Yamane; Ewida, Amr; Sianati, Bahareh; Qureshi, Adnan I; Koubeissi, Mohamad Z

2017-08-01

Traumatic brain injury (TBI) is a well-known risk factor for seizures. We aimed to identify the frequency and risk factors for seizure occurrence during hospitalization for TBI. We used ICD-9-CM codes to identify patients 18 years of age or older from the National Trauma Data Bank who were admitted with TBI. We also used ICD-9-CM codes to identify the subset who had seizures during hospitalization. Patient demographics, comorbidities, Glasgow Coma Scale (GCS) score, Injury Severity Score Abbreviated Injury Scale (ISSAIS), in-hospital complications, and discharge disposition were compared in the seizure group (SG) and no-seizure group (NSG). A total of 1559 patients had in-hospital seizures, comprising 0.4% of all patients admitted with TBI. The mean age of SG was 3 years older than NSG [51 vs. 48; p < 0.0001]. African-American ethnicity (20 vs. 12%, p < 0.0001) and moderate TBI (8 vs. 4%, p < 0.0001) were more common in SG. History of alcohol dependence was more common in the SG (25 vs. 11%, p < 0.0001). Fall was the most common mechanism of injury in SG (56 vs. 36% in NSG; p < 0.0001). Subdural hematoma was more common in SG (31 vs. 21%, p < 0.0001). SG had higher rates of pneumonia, ARDS, acute kidney injury, and increased ICP. The average length of hospital stay was significantly higher in SG (10 vs. 6 days, p < 0.0001), and these patients had higher rate of discharge to nursing facility (32 vs. 25%, p < 0.0001). In-hospital seizures occur in 0.4% of all TBI patients. Although infrequent, seizure occurrence is associated with higher rates of hospital complications such as pneumonia and ARDS and is an independent predictor of longer hospital stay and worse hospital outcome.

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

Association of Severe Traumatic Brain Injury Patient Outcomes With Duration of Cerebrovascular Autoregulation Impairment Events.

PubMed

Preiksaitis, Aidanas; Krakauskaite, Solventa; Petkus, Vytautas; Rocka, Saulius; Chomskis, Romanas; Dagi, Teodoro Forcht; Ragauskas, Arminas

2016-07-01

Cerebrovascular autoregulation (CA) is an important hemodynamic mechanism that protects the brain against inappropriate fluctuations in cerebral blood flow in the face of changing cerebral perfusion pressure. Temporal CA failure is associated with worse outcomes in various acute neurological diseases. An integrative approach is presently used according to the existing paradigm for the association of series of temporal CA impairments with the outcomes of patients with traumatic brain injury (TBI). To explore the influence of the duration of CA impairment events on severe TBI patient outcomes. Patient age was also included in the analysis of the prospectively collected clinical data. CA monitoring included 33 prospective severe TBI patients. The pressure reactivity index [PRx(t)] was continuously monitored to collect information on the dynamics of CA status and to analyze associations between the duration of the longest CA impairment event and patient outcomes. The Glasgow outcome scale and the duration of the longest CA impairment were negatively correlated. The duration of autoregulation impairment significantly correlated with worse outcomes. Multidimensional representation of Glasgow outcome scale plots showed that better outcomes were obtained for younger patients (age < 47 years) and those whose longest CA impairment event was shorter than 40 minutes if PRx(t) was above 0.7 in the CA impairment event. Unfavorable outcomes for TBI patients are more significantly associated with the duration of the single longest CA impairment episode at a high PRx(t) value, rather than with averaged PRx(t) values or the average time of all CA impairment episodes. ABP, arterial blood pressureABP(t), continuous reference arterial blood pressureCA, cerebrovascular autoregulationCBF, cerebral blood flowCPP, cerebral perfusion pressureGOS, Glasgow outcome scaleGOSHD, Glasgow outcome scale after hospital dischargeGOS6M, Glasgow outcome scale at 6 months after discharge

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

Effects of Patient Pre-Injury and Injury Characteristics on Acute Rehabilitation Outcomes for Traumatic Brain Injury

PubMed Central

Corrigan, John D.; Horn, Susan D.; Barrett, Ryan S.; Smout, Randall J.; Bogner, Jennifer; Hammond, Flora M.; Brandstater, Murray E.; Majercik, Sarah

2015-01-01

Objective To examine associations of patient and injury characteristics with outcomes at inpatient rehabilitation discharge and 9 months post-discharge for patients with traumatic brain injury (TBI) Design Prospective, longitudinal observational study Setting 10 inpatient rehabilitation centers (9 US, 1 Canada) Participants Consecutive patients (n=2130) enrolled between 2008 and 2011, admitted for inpatient rehabilitation after index TBI injury, and divided into 5 subgroups based on rehabilitation admission FIM Cognitive score Interventions Not applicable Main Outcome Measures Rehabilitation length of stay, discharge to home, and FIM at discharge and 9 months post-discharge. Results Severity indices increased explained variation in outcomes beyond that accounted for by patient characteristics. FIM Motor scores were generally the most predictable. Higher functioning subgroups had more predictable outcomes then subgroups with lower cognitive function at admission. Age at injury, time from injury to rehabilitation admission, and functional independence at rehabilitation admission were the most consistent predictors across all outcomes and subgroups. Conclusions Findings from previous studies of the relationships among patient and injury characteristics and rehabilitation outcomes were largely replicated. Discharge outcomes were most strongly associated with injury severity characteristics; while predictors of functional independence at 9 months post-discharge included both patient and injury characteristics. PMID:26212398

Total Body Irradiation Compared With BEAM: Long-Term Outcomes of Peripheral Blood Autologous Stem Cell Transplantation for Non-Hodgkin's Lymphoma

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

Liu, Hong-Wei; University of Manitoba, Winnipeg, MB; Seftel, Matthew D.

Purpose: The optimal preparative regimen for non-Hodgkin's lymphoma patients undergoing autologous peripheral blood stem cell transplantation (PBSCT) is unknown. We compared a total body irradiation (TBI)-based regimen with a chemotherapy-alone regimen. Methods and Materials: A retrospective cohort study was performed at a Canadian cancer center. The TBI regimen consisted of cyclophosphamide, etoposide, and TBI 12 Gy in six fractions (CY/E/TBI). The chemotherapy-alone regimen consisted of carmustine, etoposide, cytarabine, and melphalan (BEAM). We compared the acute and long-term toxicities, disease relapse-free survival, and overall survival (OS). Results: Of 73 patients, 26 received CY/E/TBI and 47 received BEAM. The median follow-up formore » the CY/E/TBI group was 12.0 years and for the BEAM group was 7.3 years. After PBSCT, no differences in acute toxicity were seen between the two groups. The 5-year disease relapse-free survival rate was 50.0% and 50.7% in the CY/E/TBI and BEAM groups, respectively (p = .808). The 5-year OS rate was 53.9% and 63.8% for the CY/E/TBI and BEAM groups, respectivey (p = .492). The univariate analysis results indicated that patients with Stage IV, with chemotherapy-resistant disease, and who had received PBSCT before 2000 had inferior OS. A three-way categorical analysis revealed that transplantation before 2000, rather than the conditioning regimen, was a more important predictive factor of long-term outcome (p = .034). Conclusion: A 12-Gy TBI-based conditioning regimen for PBSCT for non-Hodgkin's lymphoma resulted in disease relapse-free survival and OS similar to that after BEAM. PBSCT before 2000, and not the conditioning regimen, was an important predictor of long-term outcomes. TBI was not associated with more acute toxicity or pneumonitis. We found no indication that the TBI regimen was inferior or superior to BEAM.« less

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.…

Severe Pulmonary Toxicity After Myeloablative Conditioning Using Total Body Irradiation: An Assessment of Risk Factors

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

Kelsey, Chris R., E-mail: kelse003@mc.duke.edu; Horwitz, Mitchell E.; Chino, Junzo P.

2011-11-01

Purpose: To assess factors associated with severe pulmonary toxicity after myeloablative conditioning using total body irradiation (TBI) followed by allogeneic stem cell transplantation. Methods and Materials: A total of 101 adult patients who underwent TBI-based myeloablative conditioning for hematologic malignancies at Duke University between 1998 and 2008 were reviewed. TBI was combined with high-dose cyclophosphamide, melphalan, fludarabine, or etoposide, depending on the underlying disease. Acute pulmonary toxicity, occurring within 90 days of transplantation, was scored using Common Terminology Criteria for Adverse Events version 3.0. Actuarial overall survival and the cumulative incidence of acute pulmonary toxicity were calculated via the Kaplan-Meiermore » method and compared using a log-rank test. A binary logistic regression analysis was performed to assess factors independently associated with acute severe pulmonary toxicity. Results: The 90-day actuarial risk of developing severe (Grade 3-5) pulmonary toxicity was 33%. Actuarial survival at 90 days was 49% in patients with severe pulmonary toxicity vs. 94% in patients without (p < 0.001). On multivariate analysis, the number of prior chemotherapy regimens was the only factor independently associated with development of severe pulmonary toxicity (odds ratio, 2.7 per regimen). Conclusions: Severe acute pulmonary toxicity is prevalent after TBI-based myeloablative conditioning regimens, occurring in approximately 33% of patients. The number of prior chemotherapy regimens appears to be an important risk factor.« less

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.

Risk and mortality of traumatic brain injury in stroke patients: two nationwide cohort studies.

PubMed

Chou, Yi-Chun; Yeh, Chun-Chieh; Hu, Chaur-Jong; Meng, Nai-Hsin; Chiu, Wen-Ta; Chou, Wan-Hsin; Chen, Ta-Liang; Liao, Chien-Chang

2014-01-01

Patients with stroke had higher incidence of falls and hip fractures. However, the risk of traumatic brain injury (TBI) and post-TBI mortality in patients with stroke was not well defined. Our study is to investigate the risk of TBI and post-TBI mortality in patients with stroke. Using reimbursement claims from Taiwan's National Health Insurance Research Database, we conducted a retrospective cohort study of 7622 patients with stroke and 30 488 participants without stroke aged 20 years and older as reference group. Data were collected on newly developed TBI after stroke with 5 to 8 years' follow-up during 2000 to 2008. Another nested cohort study including 7034 hospitalized patients with TBI was also conducted to analyze the contribution of stroke to post-TBI in-hospital mortality. Compared with the nonstroke cohort, the adjusted hazard ratio of TBI risk among patients with stroke was 2.80 (95% confidence interval = 2.58-3.04) during the follow-up period. Patients with stroke had higher mortality after TBI than those without stroke (10.2% vs 3.2%, P < .0001) with an adjusted relative risk (RR) of 1.46 (95% confidence interval = 1.15-1.84). Recurrent stroke (RR = 1.60), hemorrhagic stroke (RR = 1.68), high medical expenditure for stroke (RR = 1.80), epilepsy (RR = 1.79), neurosurgery (RR = 1.94), and hip fracture (RR = 2.11) were all associated with significantly higher post-TBI mortality among patients with stroke. Patients with stroke have an increased risk of TBI and in-hospital mortality after TBI. Various characteristics of stroke severity were all associated with higher post-TBI mortality. Special attention is needed to prevent TBI among these populations.

Acute epiglottitis: A review of 50 patients.

PubMed

Lon, Shafkat Ahmad; Lateef, Mohd; Sajad, Mir

2006-04-01

We reviewed 50 patients admitted to the department of Otorhinolaryngology and Head & Neck Surgery of Govt Medical College Srinagar from September 19% to September 2002 diagnosed with acute epiglottitis. Male were more commonly involved than females in the ratio of 2.8:1 with only 6 cases younger than 10 years of age. The highest incidence was in the month of January (22%). The common symptoms of acute epiglottitis were sorethroat(92%) and odynophagia(88%). Any patient with sudden onset of these symptoms should be suspected of having acute epiglottitis and should have an indirect laryngoscopy. Blood culture was obtained in 20 cases Cultures were positive only in 5 cases, out of which 4 were positive for Hemophilus influenzae type B. Throat cultures were not obtamed The primary treatment of acute epiglottitis is intravenous antibiotics, steriods, and humidified air. Treacheostomy was needed only in 4 patients. There were no deaths.

Accurate diagnosis of acute abdomen in FMF and acute appendicitis patients: how can we use procalcitonin?

PubMed

Kisacik, Bunyamin; Kalyoncu, Umut; Erol, M Fatih; Karadag, Omer; Yildiz, Mustafa; Akdogan, Ali; Kaptanoglu, Bugra; Hayran, Mutlu; Ureten, Kemal; Ertenli, Ihsan; Kiraz, Sedat; Calguneri, Meral

2007-12-01

This study was conducted to define the value of procalcitonin (PCT) levels in the differential diagnosis of abdominal familial Mediterranean fever (FMF) attacks from acute appendicitis. From October 2006 to January 2007, 28 FMF (12 males, 16 females) patients with acute abdominal attacks and 34 patients (18 males) with acute abdomen who underwent operation with the clinical diagnosis of acute appendicitis were consecutively enrolled in this study. FMF patients with concurrent infectious diseases were excluded. PCT values were measured by an immunofluorescent method using the B.R.A.H.M.S. PCT kit (B.R.A.H.M.S. Diagnostica, Berlin, Germany). Erythrocyte sedimentation rate (ESR), C-reactive proteins (CRP) and leucocyte levels were also noted. Mean disease duration in FMF patients was 9.6 +/- 8.1 years (range 2-33 years) and all were on colchicine therapy with a mean colchicine dosage of 1.2 +/- 0.4 mg/day. Among the operated patients, 5 were excluded: 3 patients had normal findings and 2 had intestinal perforation (PCT levels were 2.69 and 4.93 ng/ml, respectively) at operative and pathologic evaluation. There were no significant differences between the two groups with respect to gender and age (p was not significant (NS) for all). Acute phase reactants and PCT levels were increased in patients with FMF compared to patients with acute appendicitis (0.529[0.12 +/- 0.96] vs 0.095 [0.01-0.80] p < 0.001, respectively). PCT levels higher than 0.5 ng/ml were found in 11% (3/28) of FMF patients compared to 62% (18/29) of acute appendicitis patients (p < 0.001). Our results suggest that PCT could be a useful test in the differentiation of abdominal FMF attacks from acute appendicitis, though it should not supplant more conventional investigations.

Investigation of Multiple Frequency Ranges Using Discrete Wavelet Decomposition of Resting-State Functional Connectivity in Mild Traumatic Brain Injury Patients

PubMed Central

Chen, Haoxing; Roys, Steven; Zhuo, Jiachen; Varshney, Amitabh; Gullapalli, Rao P.

2015-01-01

Abstract The aim of this study was to investigate if discrete wavelet decomposition provides additional insight into resting-state processes through the analysis of functional connectivity within specific frequency ranges within the default mode network (DMN) that may be affected by mild traumatic brain injury (mTBI). Participants included 32 mTBI patients (15 with postconcussive syndrome [PCS+] and 17 without [PCS−]). mTBI patients received resting-state functional magnetic resonance imaging (rs-fMRI) at acute (within 10 days of injury) and chronic (6 months postinjury) time points and were compared with 31 controls (healthy control [HC]). The wavelet decomposition divides the time series into multiple frequency ranges based on four scaling factors (SF1: 0.125–0.250 Hz, SF2: 0.060–0.125 Hz, SF3: 0.030–0.060 Hz, SF4: 0.015–0.030 Hz). Within each SF, wavelet connectivity matrices for nodes of the DMN were created for each group (HC, PCS+, PCS−), and bivariate measures of strength and diversity were calculated. The results demonstrate reduced strength of connectivity in PCS+ patients compared with PCS− patients within SF1 during both the acute and chronic stages of injury, as well as recovery of connectivity within SF1 across the two time points. Furthermore, the PCS− group demonstrated greater network strength compared with controls at both time points, suggesting a potential compensatory or protective mechanism in these patients. These findings stress the importance of investigating resting-state connectivity within multiple frequency ranges; however, many of our findings are within SF1, which may overlap with frequencies associated with cardiac and respiratory activities. PMID:25808612

Investigation of Multiple Frequency Ranges Using Discrete Wavelet Decomposition of Resting-State Functional Connectivity in Mild Traumatic Brain Injury Patients.

PubMed

Sours, Chandler; Chen, Haoxing; Roys, Steven; Zhuo, Jiachen; Varshney, Amitabh; Gullapalli, Rao P

2015-09-01

The aim of this study was to investigate if discrete wavelet decomposition provides additional insight into resting-state processes through the analysis of functional connectivity within specific frequency ranges within the default mode network (DMN) that may be affected by mild traumatic brain injury (mTBI). Participants included 32 mTBI patients (15 with postconcussive syndrome [PCS+] and 17 without [PCS-]). mTBI patients received resting-state functional magnetic resonance imaging (rs-fMRI) at acute (within 10 days of injury) and chronic (6 months postinjury) time points and were compared with 31 controls (healthy control [HC]). The wavelet decomposition divides the time series into multiple frequency ranges based on four scaling factors (SF1: 0.125-0.250 Hz, SF2: 0.060-0.125 Hz, SF3: 0.030-0.060 Hz, SF4: 0.015-0.030 Hz). Within each SF, wavelet connectivity matrices for nodes of the DMN were created for each group (HC, PCS+, PCS-), and bivariate measures of strength and diversity were calculated. The results demonstrate reduced strength of connectivity in PCS+ patients compared with PCS- patients within SF1 during both the acute and chronic stages of injury, as well as recovery of connectivity within SF1 across the two time points. Furthermore, the PCS- group demonstrated greater network strength compared with controls at both time points, suggesting a potential compensatory or protective mechanism in these patients. These findings stress the importance of investigating resting-state connectivity within multiple frequency ranges; however, many of our findings are within SF1, which may overlap with frequencies associated with cardiac and respiratory activities.

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.

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.

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…

Curcumin attenuates acute inflammatory injury by inhibiting the TLR4/MyD88/NF-κB signaling pathway in experimental traumatic brain injury

PubMed Central

2014-01-01

neuron co-culture following treatment with curcumin after LPS stimulation. LPS increased TLR4 immunoreactivity and morphological activation in microglia and increased neuronal apoptosis, whereas curcumin normalized this upregulation. The increased protein levels of TLR4, MyD88 and NF-κB in microglia were attenuated by curcumin treatment. Conclusions Our results suggest that post-injury, curcumin administration may improve patient outcome by reducing acute activation of microglia/macrophages and neuronal apoptosis through a mechanism involving the TLR4/MyD88/NF-κB signaling pathway in microglia/macrophages in TBI. PMID:24669820

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.

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.

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.

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.

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.

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…

Alterations in the Timing of Huperzine A Cerebral Pharmacodynamics in the Acute Traumatic Brain Injury Setting.

PubMed

Damar, Ugur; Gersner, Roman; Johnstone, Joshua T; Kapur, Kush; Collins, Stephen; Schachter, Steven; Rotenberg, Alexander

2018-01-15

Traumatic brain injury (TBI) may affect the pharmacodynamics of centrally acting drugs. Paired-pulse transcranial magnetic stimulation (ppTMS) is a safe and noninvasive measure of cortical gamma-aminobutyric acid (GABA)-mediated cortical inhibition. Huperzine A (HupA) is a naturally occurring acetylcholinesterase inhibitor with newly discovered potent GABA-mediated antiepileptic capacity, which is reliably detected by ppTMS. To test whether TBI alters cerebral HupA pharmacodynamics, we exposed rats to fluid percussion injury (FPI) and tested whether ppTMS metrics of cortical inhibition differ in magnitude and temporal pattern in injured rats. Anesthetized adult rats were exposed to FPI or sham injury. Ninety minutes post-TBI, rats were injected with HupA or saline (0.6 mg/kg, intraperitoneally). TBI resulted in reduced cortical inhibition 90 min after the injury (N = 18) compared to sham (N = 13) controls (p = 0.03). HupA enhanced cortical inhibition after both sham injury (N = 6; p = 0.002) and TBI (N = 6; p = 0.02). The median time to maximum HupA inhibition in sham and TBI groups were 46.4 and 76.5 min, respectively (p = 0.03). This was consistent with a quadratic trend comparison that projects HupA-mediated cortical inhibition to last longer in injured rats (p = 0.007). We show that 1) cortical GABA-mediated inhibition, as measured by ppTMS, decreases acutely post-TBI, 2) HupA restores lost post-TBI GABA-mediated inhibition, and 3) HupA-mediated enhancement of cortical inhibition is delayed post-TBI. The plausible reasons of the latter include 1) low HupA volume of distribution rendering HupA confined in the intravascular compartment, therefore vulnerable to reduced post-TBI cerebral perfusion, and 2) GABAR dysfunction and increased AChE activity post-TBI.

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.

The effect of donepezil on the cognitive ability early in the course of recovery from traumatic brain injury.

PubMed

Campbell, Kelsey A; Kennedy, Richard E; Brunner, Robert C; Hollis, Sean D; Lumsden, Ross A; Novack, Thomas A

2018-05-08

To investigate the effect of donepezil on cognitive ability in patients who have sustained a traumatic brain injury (TBI). We hypothesized that donepezil, an acetylcholinesterase inhibitor, would enhance cognitive recovery beyond that of usual care in an acute rehabilitation facility. This retrospective, longitudinal analysis included 55 patients who were non-randomly prescribed donepezil during acute care and compared them to 74 patients who received usual rehabilitation treatment. All 129 patients completed neuropsychological assessment at two time points. Donepezil was increased from 5 to 10 mg 7-10 days after initiation and maintained until follow-up cognitive assessment. Primary cognitive abilities of interest included processing speed, attention and memory. Cognitive and functional abilities were assessed by a standard neuropsychological battery for TBI. Propensity scores were used to adjust for differences between groups. Mixed effect model analysis showed no significant differences between treatment and control groups on all neuropsychological subtests over time. Acute administration of donepezil did not significantly improve measures of cognitive or functional ability beyond that of treatment as usual in patients with moderate-to-severe TBI.

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

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

Low rate of delayed deterioration requiring surgical treatment in patients transferred to a tertiary care center for mild traumatic brain injury.

PubMed

Carlson, Andrew P; Ramirez, Pedro; Kennedy, George; McLean, A Robb; Murray-Krezan, Cristina; Stippler, Martina

2010-11-01

Patients with mild traumatic brain injury (mTBI) only rarely need neurosurgical intervention; however, there is a subset of patients whose condition will deteriorate. Given the high resource utilization required for interhospital transfer and the relative infrequency of the need for intervention, this study was undertaken to determine how often patients who were transferred required intervention and if there were factors that could predict that need. The authors performed a retrospective review of cases involving patients who were transferred to the University of New Mexico Level 1 trauma center for evaluation of mTBI between January 2005 and December 2009. Information including demographic data, lesion type, need for neurosurgical intervention, and short-term outcome was recorded. During the 4-year study period, 292 patients (age range newborn to 92 years) were transferred for evaluation of mTBI. Of these 292 patients, 182 (62.3%) had an acute traumatic finding of some kind; 110 (60.4%) of these had a follow-up CT to evaluate progression, whereas 60 (33.0%) did not require a follow-up CT. In 15 cases (5.1% overall), the patients were taken immediately to the operating room (either before or after the first CT). Only 4 patients (1.5% overall) had either clinical or radiographic deterioration requiring delayed surgical intervention after the second CT scan. Epidural hematoma (EDH) and subdural hematoma (SDH) were both found to be significantly associated with the need for surgery (OR 29.5 for EDH, 95% CI 6.6-131.8; OR 9.7 for SDH, 95% CI 2.4-39.1). There were no in-hospital deaths in the series, and 97% of patients were discharged with a Glasgow Coma Scale score of 15. Most patients who are transferred with mTBI who need neurosurgical intervention have a surgical lesion initially. Only a very small percentage will have a delayed deterioration requiring surgery, with EDH and SDH being more concerning lesions. In most cases of mTBI, triage can be performed by a

Cerebral hemodynamic changes of mild traumatic brain injury at the acute stage.

PubMed

Doshi, Hardik; Wiseman, Natalie; Liu, Jun; Wang, Wentao; Welch, Robert D; O'Neil, Brian J; Zuk, Conor; Wang, Xiao; Mika, Valerie; Szaflarski, Jerzy P; Haacke, E Mark; Kou, Zhifeng

2015-01-01

Mild traumatic brain injury (mTBI) is a significant public health care burden in the United States. However, we lack a detailed understanding of the pathophysiology following mTBI and its relation to symptoms and recovery. With advanced magnetic resonance imaging (MRI), we can investigate brain perfusion and oxygenation in regions known to be implicated in symptoms, including cortical gray matter and subcortical structures. In this study, we assessed 14 mTBI patients and 18 controls with susceptibility weighted imaging and mapping (SWIM) for blood oxygenation quantification. In addition to SWIM, 7 patients and 12 controls had cerebral perfusion measured with arterial spin labeling (ASL). We found increases in regional cerebral blood flow (CBF) in the left striatum, and in frontal and occipital lobes in patients as compared to controls (p = 0.01, 0.03, 0.03 respectively). We also found decreases in venous susceptibility, indicating increases in venous oxygenation, in the left thalamostriate vein and right basal vein of Rosenthal (p = 0.04 in both). mTBI patients had significantly lower delayed recall scores on the standardized assessment of concussion, but neither susceptibility nor CBF measures were found to correlate with symptoms as assessed by neuropsychological testing. The increased CBF combined with increased venous oxygenation suggests an increase in cerebral blood flow that exceeds the oxygen demand of the tissue, in contrast to the regional hypoxia seen in more severe TBI. This may represent a neuroprotective response following mTBI, which warrants further investigation.

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.

Patient Effort in Traumatic Brain Injury Inpatient Rehabilitation: Course and Associations With Age, Brain Injury Severity, and Time Postinjury

PubMed Central

Seel, Ronald T.; Corrigan, John D.; Dijkers, Marcel P.; Barrett, Ryan S.; Bogner, Jennifer; Smout, Randall J.; Garmoe, William; Horn, Susan D.

2016-01-01

Objective To describe patients' level of effort in occupational, physical, and speech therapy sessions during traumatic brain injury (TBI) inpatient rehabilitation and to evaluate how age, injury severity, cognitive impairment, and time are associated with effort. Design Prospective, multicenter, longitudinal cohort study. Setting Acute TBI rehabilitation programs. Participants Patients (N=1946) receiving 138,555 therapy sessions. Interventions Not applicable. Main Outcome Measures Effort in rehabilitation sessions rated on the Rehabilitation Intensity of Therapy Scale, FIM, Comprehensive Severity Index brain injury severity score, posttraumatic amnesia (PTA), and Agitated Behavior Scale (ABS). Results The Rehabilitation Intensity of Therapy Scale effort ratings in individual therapy sessions closely conformed to a normative distribution for all 3 disciplines. Mean Rehabilitation Intensity of Therapy Scale ratings for patients' therapy sessions were higher in the discharge week than in the admission week (P<.001). For patients who completed 2, 3, or 4 weeks of rehabilitation, differences in effort ratings (P<.001) were observed between 5 subgroups stratified by admission FIM cognitive scores and over time. In linear mixed-effects modeling, age and Comprehensive Severity Index brain injury severity score at admission, days from injury to rehabilitation admission, days from admission, and daily ratings of PTA and ABS score were predictors of level of effort (P<.0001). Conclusions Patients' level of effort can be observed and reliably rated in the TBI inpatient rehabilitation setting using the Rehabilitation Intensity of Therapy Scale. Patients who sustain TBI show varying levels of effort in rehabilitation therapy sessions, with effort tending to increase over the stay. PTA and agitated behavior are primary risk factors that substantially reduce patient effort in therapies. PMID:26212400

Frequency, risk factors, and outcomes of vancomycin-resistant Enterococcus colonization and infection in patients with newly diagnosed acute leukemia: different patterns in patients with acute myelogenous and acute lymphoblastic leukemia.

PubMed

Ford, Clyde D; Lopansri, Bert K; Haydoura, Souha; Snow, Greg; Dascomb, Kristin K; Asch, Julie; Bo Petersen, Finn; Burke, John P

2015-01-01

OBJECTIVE To determine the frequency, risk factors, and outcomes for vancomycin-resistant Enterococcus (VRE) colonization and infection in patients with newly diagnosed acute leukemia. DESIGN Retrospective clinical study with VRE molecular strain typing. SETTING A regional referral center for acute leukemia. PATIENTS Two hundred fourteen consecutive patients with newly diagnosed acute leukemia between 2006 and 2012. METHODS All patients had a culture of first stool and weekly surveillance for VRE. Clinical data were abstracted from the Intermountain Healthcare electronic data warehouse. VRE molecular typing was performed utilizing the semi-automated DiversiLab System. RESULTS The rate of VRE colonization was directly proportional to length of stay and was higher in patients with acute lymphoblastic leukemia. Risk factors associated with colonization include administration of corticosteroids (P=0.004) and carbapenems (P=0.009). Neither a colonized prior room occupant nor an increased unit colonization pressure affected colonization risk. Colonized patients with acute myelogenous leukemia had an increased risk of VRE bloodstream infection (BSI, P=0.002). Other risk factors for VRE BSI include severe neutropenia (P=0.04) and diarrhea (P=0.008). Fifty-eight percent of BSI isolates were identical or related by molecular typing. Eighty-nine percent of bloodstream isolates were identical or related to stool isolates identified by surveillance cultures. VRE BSI was associated with increased costs (P=0.0003) and possibly mortality. CONCLUSIONS VRE colonization has important consequences for patients with acute myelogenous leukemia undergoing induction therapy. For febrile neutropenic patients with acute myelogenous leukemia, use of empirical antibiotic regimens that avoid carbapenems and include VRE coverage may be helpful in decreasing the risks associated with VRE BSI.

Utility of the Military Acute Concussion Evaluation as a screening tool for mild traumatic brain injury in a civilian trauma population.

PubMed

Stone, Melvin E; Safadjou, Saman; Farber, Benjamin; Velazco, Nerissa; Man, Jianliang; Reddy, Srinivas H; Todor, Roxanne; Teperman, Sheldon

2015-07-01

Mild traumatic brain injury (mTBI) constitutes 75% of more than 1.5 million traumatic brain injuries annually. There exists no consensus on point-of-care screening for mTBI. The Military Acute Concussion Evaluation (MACE) is a quick and easy test used by the US Army to screen for mTBI; however, its utility in civilian trauma is unclear. It has two parts: a history section and the Standardized Assessment of Concussion (SAC) score (0-30) previously validated in sports injury. As a performance improvement project, our institution sought to evaluate the MACE as a concussion screening tool that could be used by housestaff in a general civilian trauma population. From June 2013 to May 2014, patients 18 years to 65 years old with suspected concussion were given the MACE within 72 hours of admission to our urban Level I trauma center. Patients with a positive head computed tomography were excluded. Demographic data and MACE scores were recorded in prospect. Concussion was defined as loss of consciousness and/or posttraumatic amnesia; concussed patients were compared with those nonconcussed. Sensitivity and specificity for each respective MACE score were used to plot a receiver operating characteristic (ROC) curve. An ROC curve area of 0.8 was set as the benchmark for a good screening test to distinguish concussion from nonconcussion. There were 84 concussions and 30 nonconcussed patients. Both groups were similar; however, the concussion group had a lower mean MACE score than the nonconcussed patients. Data analysis demonstrated the sensitivity and specificity of a range of MACE scores used to generate an ROC curve area of only 0.65. The MACE showed a lower mean score for individuals with concussion, defined by loss of consciousness and/or posttraumatic amnesia. However, the ROC curve area of 0.65 highly suggests that MACE alone would be a poor screening test for mTBI in a general civilian trauma population. Diagnostic study, level II.

Loss of PAFR prevents neuroinflammation and brain dysfunction after traumatic brain injury

PubMed Central

Yin, Xiang-Jie; Chen, Zhen-Yan; Zhu, Xiao-Na; Hu, Jin-Jia

2017-01-01

Traumatic brain injury (TBI) is a principal cause of death and disability worldwide, which is a major public health problem. Death caused by TBI accounts for a third of all damage related illnesses, which 75% TBI occurred in low and middle income countries. With the increasing use of motor vehicles, the incidence of TBI has been at a high level. The abnormal brain functions of TBI patients often show the acute and long-term neurological dysfunction, which mainly associated with the pathological process of malignant brain edema and neuroinflammation in the brain. Owing to the neuroinflammation lasts for months or even years after TBI, which is a pivotal causative factor that give rise to neurodegenerative disease at late stage of TBI. Studies have shown that platelet activating factor (PAF) inducing inflammatory reaction after TBI could not be ignored. The morphological and behavioral abnormalities after TBI in wild type mice are rescued by general knockout of PAFR gene that neuroinflammation responses and cognitive ability are improved. Our results thus define a key inflammatory molecule PAF that participates in the neuroinflammation and helps bring about cerebral dysfunction during the TBI acute phase. PMID:28094295

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

Bacteriology of aspiration pneumonia in patients with acute coma.

PubMed

Lauterbach, Enise; Voss, Frederik; Gerigk, Roland; Lauterbach, Michael

2014-12-01

Loss of protective airway reflexes in patients with acute coma puts these patients at risk of aspiration pneumonia complicating the course of the primary disease. Available data vary considerably with regard to bacteriology, role of anaerobic bacteria, and antibiotic treatment. Our objective was to research the bacteriology of aspiration pneumonia in acute coma patients who were not pre-treated with antibiotics or hospitalized within 30 days prior to the event. We prospectively analyzed 127 patient records from adult patients admitted, intubated and ventilated to a tertiary medical intensive care unit with acute coma. Bacteriology and antibiotic resistance testing from tracheal aspirate sampled within 24 h after admission, blood cultures, ICU scores (APACHE II, SOFA), hematology, and clinical chemistry were assessed. Patients were followed up until death or hospital discharge. The majority of patients with acute coma suffered from acute cardiovascular disorders, predominantly myocardial infarction, followed by poisonings, and coma of unknown cause. In a majority of our patients, microaspiration resulted in overt infection. Most frequently S. aureus, H. influenzae, and S. pneumoniae were isolated. Anaerobic bacteria (Bacteroides spec., Fusobacteria, Prevotella spec.) were isolated from tracheal aspirate in a minority of patients, and predominantly as part of a mixed infection. Antibiotic monotherapy with a 2nd generation cephalosporin, or a 3rd generation gyrase inhibitor, was most effective in our patients regardless of the presence of anaerobic bacteria.

Structure, Process, and Culture of Intensive Care Units Treating Patients with Severe Traumatic Brain Injury: Survey of Centers Participating in the American College of Surgeons Trauma Quality Improvement Program.

PubMed

Alali, Aziz S; McCredie, Victoria A; Mainprize, Todd G; Gomez, David; Nathens, Avery B

2017-10-01

Outcome after severe traumatic brain injury (TBI) differs substantially between hospitals. Explaining this variation begins with understanding the differences in structures and processes of care, particularly at intensive care units (ICUs) where acute TBI care takes place. We invited trauma medical directors (TMDs) from 187 centers participating in the American College of Surgeons Trauma Quality Improvement Program (ACS TQIP) to complete a survey. The survey domains included ICU model, type, availability of specialized units, staff, training programs, standard protocols and order sets, approach to withdrawal of life support, and perceived level of neurosurgeons' engagement in the ICU management of TBI. One hundred forty-two TMDs (76%) completed the survey. Severe TBI patients are admitted to dedicated neurocritical care units in 52 hospitals (37%), trauma ICUs in 44 hospitals (31%), general ICUs in 34 hospitals (24%), and surgical ICUs in 11 hospitals (8%). Fifty-seven percent are closed units. Board-certified intensivists directed 89% of ICUs, whereas 17% were led by neurointensivists. Sixty percent of ICU directors were general surgeons. Thirty-nine percent of hospitals had critical care fellowships and 11% had neurocritical care fellowships. Fifty-nine percent of ICUs had standard order sets and 61% had standard protocols specific for TBI, with the most common protocol relating to intracranial pressure management (53%). Only 43% of TMDs were satisfied with the current level of neurosurgeons' engagement in the ICU management of TBI; 46% believed that neurosurgeons should be more engaged; 11% believed they should be less engaged. In the largest survey of North American ICUs caring for TBI patients, there is substantial variation in the current approaches to ICU care for TBI, highlighting multiple opportunities for comparative effectiveness research.

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.

Acute pain management in patients with persistent pain.

PubMed

Quinlan, Jane; Carter, Kim

2012-06-01

Over the past 20 years, prescriptions of opioids for chronic pain have increased dramatically. This review addresses the difficulties in managing acute pain in this growing group of patients and discusses evidence relating to opioid tolerance and hyperalgesia and new avenues of research in specific painful conditions. There is accumulating evidence surrounding the dangers of high-dose opioids and the risk of overdose and death. Employing nonopioid analgesics and disease-modifying drugs to cover an acute exacerbation of pain will thus limit escalating opioid doses. In specific diseases, the role of oxidative stress and the disruption of calcium homeostasis may provide treatment targets in acute pancreatitis; the identification of psychological stressors may decrease the frequency of acute exacerbations of abdominal pain; modifying the adhesion of sickle cells to inflamed endothelium may reduce vaso-occlusive crises; while vertebroplasty and calcitonin appear to improve pain and functioning after osteoporotic vertebral fractures. Much of the evidence regarding the acute pain management of chronic pain patients is extrapolated from studies of opioid-naïve patients undergoing surgery. More focused research is needed to ascertain whether this model is an appropriate one to follow for such a complex group of patients.

Reduced incidence of interstitial pneumonitis after allogeneic hematopoietic stem cell transplantation using a modified technique of total body irradiation.

PubMed

Chiang, Yun; Tsai, Cheng-Hong; Kuo, Sung-Hsin; Liu, Chieh-Yu; Yao, Ming; Li, Chi-Cheng; Huang, Shang-Yi; Ko, Bor-Sheng; Lin, Chien-Ting; Hou, Hsin-An; Chou, Wen-Chien; Liu, Jia-Hau; Lin, Chien-Chin; Wu, Shang-Ju; Hsu, Szu-Chun; Chen, Yao-Chang; Lin, Kai-Hsin; Lin, Dong-Tsamn; Chou, Hsien-Tang; Lu, Meng-Yu; Yang, Yung-Li; Chang, Hsiu-Hao; Liu, Ming-Chih; Liao, Xiu-Wen; Wu, Jian-Kuen; Chou, Sheng-Chieh; Cheng, Chieh-Lung; Chen, Chien-Yuan; Tsay, Woei; Tien, Hwei-Fang; Tang, Jih-Luh; Chen, Yu-Hsuan

2016-11-10

Allogeneic hematopoietic stem cell transplantation is a curative-intent treatment for patients with high-risk hematologic diseases. However, interstitial pneumonitis (IP) and other toxicities remain major concerns after total body irradiation (TBI). We have proposed using linear accelerators with rice-bag compensators for intensity modulation (IM-TBI), as an alternative to the traditional cobalt-60 teletherapy with lung-shielding technique (Co-TBI). Patients who received a TBI-based myeloablative conditioning regimen between 1995 and 2014 were recruited consecutively. Before March 2007, TBI was delivered using Co-TBI (n = 181); afterward, TBI was administered using IM-TBI (n = 126). Forty-four patients developed IP; of these cases, 19 were idiopathic. The IP-related mortality rate was 50% in the total IP cohort and 63% in the idiopathic subgroup. The 1-year cumulative incidences of IP and idiopathic IP were 16.5% and 7.4%, respectively; both rates were significantly higher in the Co-TBI group than in the IM-TBI group. Multivariate analysis revealed that Co-TBI was an independent prognostic factor for both total and idiopathic IP. In the acute myeloid leukemia subgroup, patients with different TBI techniques had similar outcomes for both overall and relapse-free survival. In conclusion, IM-TBI is an easy and effective TBI technique that could substantially reduce the complication rate of IP without compromising treatment efficacy.

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.

Children and youth with non-traumatic brain injury: a population based perspective.

PubMed

Chan, Vincy; Pole, Jason D; Keightley, Michelle; Mann, Robert E; Colantonio, Angela

2016-07-20

Children and youth with non-traumatic brain injury (nTBI) are often overlooked in regard to the need for post-injury health services. This study provided population-based data on their burden on healthcare services, including data by subtypes of nTBI, to provide the foundation for future research to inform resource allocation and healthcare planning for this population. A retrospective cohort study design was used. Children and youth with nTBI in population-based healthcare data were identified using International Classification of Diseases Version 10 codes. The rate of nTBI episodes of care, demographic and clinical characteristics, and discharge destinations from acute care and by type of nTBI were identified. The rate of pediatric nTBI episodes of care was 82.3 per 100,000 (N = 17,977); the average stay in acute care was 13.4 days (SD = 25.6 days) and 35% were in intensive care units. Approximately 15% were transferred to another inpatient setting and 6% died in acute care. By subtypes of nTBI, the highest rates were among those with a diagnosis of toxic effect of substances (22.7 per 100,000), brain tumours (18.4 per 100,000), and meningitis (15.4 per 100,000). Clinical characteristics and discharge destinations from the acute care setting varied by subtype of nTBI; the proportion of patients that spent at least one day in intensive care units and the proportion discharged home ranged from 25.9% to 58.2% and from 50.6% to 76.4%, respectively. Children and youth with nTBI currently put an increased demand on the healthcare system. Active surveillance of and in-depth research on nTBI, including subtypes of nTBI, is needed to ensure that timely, appropriate, and targeted care is available for this pediatric population.

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

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.

Phase II trial of vindesine in patients with acute leukemia.

PubMed

Sklaroff, R B; Arlin, Z; Young, C W

1979-01-01

Vindesine was administered to 18 patients with acute leukemia who had failed conventional chemotherapy. Each course of therapy consisted of an iv bolus infusion at a dose of 1-2 mg/m2 given daily x 5-10 days. Of 13 patients with acute lymphoblastic leukemia, two had partial remissions which lasted 2 and 3 months and five had minor responses. One of three patients with acute nonlymphoblastic leukemia and one of two patients with blastic crisis of chronic myelogenous leukemia each had a minor response. The data suggest that vindesine has activity in the treatment of acute leukemia.

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.

Hypnotics use but not insomnia increased the risk of dementia in traumatic brain injury patients.

PubMed