Browsing by Subject "traumatic brain injury"
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Item Advanced Therapy in Traumatic Brain Injury Inpatient Rehabilitation: Effects on Outcomes During the First Year after Discharge(Elsevier, 2019) Timpson, Misti; Hade, Erinn M.; Beaulieu, Cynthia; Horn, Susan D.; Hammond, Flora M.; Peng, Juan; Montgomery, Erin; Giuffrida, Clare; Gilchrist, Kamie; Lash, Aubrey; Dijkers, Marcel; Corrigan, John D.; Bogner, Jennifer; Physical Medicine and Rehabilitation, School of MedicineObjective To use causal inference methods to determine if receipt of a greater proportion inpatient rehabilitation treatment focused on higher level functions, e.g. executive functions, ambulating over uneven surfaces (Advanced Therapy, AdvTx) results in better rehabilitation outcomes. Design A cohort study using propensity score methods applied to the TBI-Practice-Based Evidence (TBI-PBE) database, a database consisting of multi-site, prospective, longitudinal observational data. Setting Acute inpatient rehabilitation (IRF). Participants Patients enrolled in the TBI-PBE study (n=1843), aged 14 years or older, who sustained a severe, moderate, or complicated mild TBI, receiving their first IRF admission to one of 9 sites in the US, and consented to follow-up 3 and 9 months post discharge from inpatient rehabilitation. Interventions Not applicable. Main Outcome Measures: Participation Assessment with Recombined Tools-Objective-17, FIMTM Motor and Cognitive scores, Satisfaction with Life Scale, and Patient Health Questionnaire-9. Results Controlling for measured potential confounders, increasing the percentage of AdvTx during inpatient TBI rehabilitation was found to be associated with better community participation, functional independence, life satisfaction, and decreased likelihood of depression during the year following discharge from inpatient rehabilitation. Participants who began rehabilitation with greater disability experienced larger gains on some outcomes than those who began rehabilitation with more intact abilities. Conclusions Increasing the proportion of treatment targeting higher level functions appears to have no detrimental and a small, beneficial effect on outcome. Caution should be exercised when inferring causality given that a large number of potential confounders could not be completely controlled with propensity score methods. Further, the extent to which unmeasured confounders influenced the findings is not known and could be of particular concern due to the potential for the patient’s recovery trajectory to influence therapists’ decisions to provide a greater amount AdvTx.Item Associations between neuropsychiatric and health status outcomes in individuals with probable mTBI(Elsevier, 2019-02) Bomyea, Jessica; Flashman, Laura A.; Zafonte, Ross; Andaluz, Norberto; Coimbra, Raul; George, Mark S.; Grant, Gerald A.; Marx, Christine E.; McAllister, Thomas W.; Shutter, Lori; Lang, Ariel J.; Stein, Murray B.; Psychiatry, School of MedicineMild traumatic brain injury (mTBI) is a common occurrence, and may impact distal outcomes in a subgroup of individuals. Improved characterization of health outcomes and identification of factors associated with poor outcomes is needed to better understand the impact of mTBI, particularly in those with co-occurring posttraumatic stress disorder (PTSD). Participants in a data repository of the Injury and Traumatic Stress (INTRuST) Clinical Consortium (n = 625) completed functional disability [FD] and health-related quality of life [HRQOL] questionnaires, and a subset completed a neuropsychological assessment. FD and HRQOL were compared among participants with probable mTBI (mTBI), probable mTBI with PTSD (mTBI/PTSD), and health comparison participants (HC). Associations between symptoms, neuropsychological performance, and health outcomes were examined in those with probable mTBI with and without PTSD (n = 316). Individuals in the mTBI/PTSD group endorsed poorer health outcomes than those in the mTBI group, who endorsed poorer outcomes than those in the HC group. Individuals in either mTBI group performed worse than those in the HC on verbal learning and memory and psychomotor speed. Health outcomes were correlated with mental health and postconcussive symptoms, as well as neuropsychological variables. mTBI may adversely impact self-reported health, with the greatest effect observed in individuals with co-occurring mTBI/PTSD.Item Automated monitoring of early neurobehavioral changes in mice following traumatic brain injury(Medknow Publications, 2016-02) Qu, Wenrui; Liu, Nai-Kui; Xie, Xin-Min Simon; Li, Rui; Xu, Xiao-Ming; Department of Neurological Surgery, IU School of MedicineTraumatic brain injury often causes a variety of behavioral and emotional impairments that can develop into chronic disorders. Therefore, there is a need to shift towards identifying early symptoms that can aid in the prediction of traumatic brain injury outcomes and behavioral endpoints in patients with traumatic brain injury after early interventions. In this study, we used the SmartCage system, an automated quantitative approach to assess behavior alterations in mice during an early phase of traumatic brain injury in their home cages. Female C57BL/6 adult mice were subjected to moderate controlled cortical impact (CCI) injury. The mice then received a battery of behavioral assessments including neurological score, locomotor activity, sleep/wake states, and anxiety-like behaviors on days 1, 2, and 7 after CCI. Histological analysis was performed on day 7 after the last assessment. Spontaneous activities on days 1 and 2 after injury were significantly decreased in the CCI group. The average percentage of sleep time spent in both dark and light cycles were significantly higher in the CCI group than in the sham group. For anxiety-like behaviors, the time spent in a light compartment and the number of transitions between the dark/light compartments were all significantly reduced in the CCI group than in the sham group. In addition, the mice suffering from CCI exhibited a preference of staying in the dark compartment of a dark/light cage. The CCI mice showed reduced neurological score and histological abnormalities, which are well correlated to the automated behavioral assessments. Our findings demonstrate that the automated SmartCage system provides sensitive and objective measures for early behavior changes in mice following traumatic brain injury.Item Blood Purification by Non-Selective Hemoadsorption Prevents Death after Traumatic Brain Injury and Hemorrhagic Shock in Rats(Wolters Kluwer, 2018-09) McKinley, Todd O.; Lei, Zhigang; Kalbas, Yannik; White, Fletcher A.; Shi, Zhongshang; Wu, Fan; Xu, Zao C.; Rodgers, Richard B.; Anesthesia, School of MedicineBackground Patients who sustain traumatic brain injury (TBI) and concomitant hemorrhagic shock (HS) are at high risk of high-magnitude inflammation which can lead to poor outcomes and death. Blood purification by hemoadsorption (HA) offers an alternative intervention to reduce inflammation after injury. We tested the hypothesis that HA would reduce mortality in a rat model of TBI and HS. Methods Male Sprague Dawley rats were subjected to a combined injury of a controlled cortical impact (CCI) to their brain and pressure-controlled hemorrhagic shock (HS). Animals were subsequently instrumented with an extracorporeal blood circuit that passed through a cartridge for sham or experimental treatment. In experimental animals, the treatment cartridge was filled with proprietary beads (Cytosorbents; Monmouth Junction, NJ) that removed circulating molecules between 5 KDa and 60 KDa. Sham rats had equivalent circulation but no blood purification. Serial blood samples were analyzed with multiplex technology to quantify changes in a trauma-relevant panel of immunologic mediators. The primary outcome was survival to 96hr post-injury. Results HA improved survival from 47% in sham treated rats to 86% in HA treated rats. There were no treatment-related changes in histologic appearance. HA affected biomarker concentrations both during the treatment and over the ensuing four days after injury. Distinct changes in biomarker concentrations were also measured in survivor and non-survivor rats from the entire cohort of rats indicating biomarker patterns associated with survival and death after injury. Conclusions Blood purification by non-selective HA is an effective intervention to prevent death in a combined TBI/HS rat model. HA changed circulating concentrations of multiple inmmunologically active mediators during the treatment time frame and after treatment. HA has been safely implemented in human patients with sepsis and may be a treatment option after injury.Item Cellular players that shape evolving pathology and neurodegeneration following traumatic brain injury(Elsevier, 2018) Puntambekar, Shweta S.; Saber, Maha; Lamb, Bruce T.; Kokiko-Cochran, Olga N.; Medical and Molecular Genetics, School of MedicineTraumatic brain injury (TBI) is one of the leading causes of death and disability worldwide, and has emerged as a critical risk factor for multiple neurodegenerative diseases, particularly Alzheimer’s disease (AD). How the inflammatory cascade resulting from mechanical stress, axonal shearing and the loss of neurons and glia following initial impact in TBI, contributes to the development of AD-like disease is unclear. Neuroinflammation, characterized by blood-brain barrier (BBB) dysfunction and activation of brain-resident microglia and astrocytes, resulting in secretion of inflammatory mediators and subsequent recruitment of peripheral immune cells has been the focus of extensive research in attempts to identify drug-targets towards improving functional outcomes post TBI. While knowledge of intricate cellular interactions that shape lesion pathophysiology is incomplete, a major limitation in the field is the lack of understanding of how distinct cell types differentially alter TBI pathology. The aim of this review is to highlight functional differences between populations of bone marrow derived, infiltrating monocytes/macrophages and brain-resident microglia based on differential expression of the chemokine receptors CCR2 and CX3CR1. This review will focus on how unique subsets of mononuclear phagocytes shape TBI pathophysiology, neurotoxicity and BBB function, in a disease-stage dependent manner. Additionally, this review summarizes the role of multiple microglia and macrophage receptors, namely CCR2, CX3CR1 and Triggering Receptor Expressed on Myeloid Cells-2 (TREM2) in pathological neuroinflammation and neurodegeneration vs. recovery following TBI. TREM2 has been implicated in mediating AD-related pathology, and variants in TREM2 are particularly important due to their correlation with exacerbated neurodegeneration. Finally, this review highlights behavioral outcomes associated with microglial vs. macrophage variances, the need for novel treatment strategies that target unique subpopulations of peripheral macrophages, and the importance of development of therapeutics to modulate inflammatory functions of brain-resident microglia at specific stages of TBI.Item Characterizing health care utilization following hospitalization for a traumatic brain injury: a retrospective cohort study(Taylor & Francis, 2021) Eliacin, Johanne; Yang, Ziyi; Kean, Jacob; Dixon, Brian E.; Psychiatry, School of MedicineObjective: The purpose of this study was to characterize health services utilization among individuals hospitalized with a traumatic brain injury (TBI) 1-year post-injury. Methods: Using a retrospective cohort design, adult patients (n = 32, 042) hospitalized with a traumatic brain injury between 2005 and 2014 were selected from a statewide traumatic brain injury registry. Data on health services utilization for 1-year post-injury were extracted from electronic medical and administrative records. Descriptive statistics and logistic regression were used to characterize the cohort and a subgroup of superutilizers of health services. Results: One year after traumatic brain injury, 56% of participants used emergency department services, 80% received inpatient services, and 93% utilized outpatient health services. Superutilizers had ≥3 emergency department visits, ≥3 inpatient admissions, or ≥26 outpatient visits 1-year post-injury. Twenty-six percent of participants were superutilizers of emergency department services, 30% of inpatient services, and 26% of outpatient services. Superutilizers contributed to 81% of emergency department visits, 70% of inpatient visits, and 60% of outpatient visits. Factors associated with being a superutilizer included sex, race, residence, and insurance type. Conclusions: Several patient characteristics and demographic factors influenced patients’ healthcare utilization post-TBI. Findings provide opportunities for developing targeted interventions to improve patients’ health and traumatic brain injury-related healthcare delivery.Item Comparison of Head Impact Exposure Between Concussed Football Athletes and Matched Controls: Evidence for a Possible Second Mechanism of Sport-Related Concussion(Springer, 2018) Stemper, Brian D.; Shah, Alok S.; Harezlak, Jaroslaw; Rowson, Steven; Mihalik, Jason P.; Duma, Stefan M.; Riggen, Larry D.; Brooks, Alison; Cameron, Kenneth L.; Campbell, Darren; DiFiori, John P.; Giza, Christopher C.; Guskiewicz, Kevin M.; Jackson, Jonathan; McGinty, Gerald T.; Svoboda, Steven J.; McAllister, Thomas W.; Broglio, Steven P.; McCrea, Michael; Psychiatry, School of MedicineStudies of football athletes have implicated repetitive head impact exposure in the onset of cognitive and brain structural changes, even in the absence of diagnosed concussion. Those studies imply accumulating damage from successive head impacts reduces tolerance and increases risk for concussion. Support for this premise is that biomechanics of head impacts resulting in concussion are often not remarkable when compared to impacts sustained by athletes without diagnosed concussion. Accordingly, this analysis quantified repetitive head impact exposure in a cohort of 50 concussed NCAA Division I FBS college football athletes compared to controls that were matched for team and position group. The analysis quantified the number of head impacts and risk weighted exposure both on the day of injury and for the season to the date of injury. 43% of concussed athletes had the most severe head impact exposure on the day of injury compared to their matched control group and 46% of concussed athletes had the most severe head impact exposure for the season to the date of injury compared to their matched control group. When accounting for date of injury or season to date of injury, 72% of all concussed athletes had the most or second most severe head impact exposure compared to their matched control group. These trends associating cumulative head impact exposure with concussion onset were stronger for athletes that participated in a greater number of contact activities. For example, 77% of athletes that participated in ten or more days of contact activities had greater head impact exposure than their matched control group. This unique analysis provided further evidence for the role of repetitive head impact exposure as a predisposing factor for the onset of concussion. The clinical implication of these findings supports contemporary trends of limiting head impact exposure for college football athletes during practice activities in an effort to also reduce risk of concussive injury.Item Cumulative Effects of Prior Concussion and Primary Sport Participation on Brain Morphometry in Collegiate Athletes: A Study From the NCAA–DoD CARE Consortium(Frontiers, 2020-07-28) Brett, Benjamin L.; Bobholz, Samuel A.; España, Lezlie Y.; Huber, Daniel L.; Mayer, Andrew R.; Harezlak, Jaroslaw; Broglio, Steven P.; McAllister, Thomas W.; McCrea, Michael A.; Meier, Timothy B.; Investigators CARE Consortium; Psychiatry, School of MedicinePrior studies have reported long-term differences in brain structure (brain morphometry) as being associated with cumulative concussion and contact sport participation. There is emerging evidence to suggest that similar effects of prior concussion and contact sport participation on brain morphometry may be present in younger cohorts of active athletes. We investigated the relationship between prior concussion and primary sport participation with subcortical and cortical structures in active collegiate contact sport and non-contact sport athletes. Contact sport athletes (CS; N = 190) and matched non-contact sport athletes (NCS; N = 95) completed baseline clinical testing and participated in up to four serial neuroimaging sessions across a 6-months period. Subcortical and cortical structural metrics were derived using FreeSurfer. Linear mixed-effects (LME) models examined the effects of years of primary sport participation and prior concussion (0, 1+) on brain structure and baseline clinical variables. Athletes with prior concussion across both groups reported significantly more baseline concussion and psychological symptoms (all ps < 0.05). The relationship between years of primary sport participation and thalamic volume differed between CS and NCS (p = 0.015), driven by a significant inverse association between primary years of participation and thalamic volume in CS (p = 0.007). Additional analyses limited to CS alone showed that the relationship between years of primary sport participation and dorsal striatal volume was moderated by concussion history (p = 0.042). Finally, CS with prior concussion had larger hippocampal volumes than CS without prior concussion (p = 0.015). Years of contact sport exposure and prior concussion(s) are associated with differences in subcortical volumes in young-adult, active collegiate athletes, consistent with prior literature in retired, primarily symptomatic contact sport athletes. Longitudinal follow-up studies in these athletes are needed to determine clinical significance of current findings.Item The Effect of Trauma Center Verification on Outcomes of Traumatic Brain Injury Patients Undergoing Interfacility Transfer(Wiley, 2021) Jenkins, Peter C.; Newgard, Craig; Surgery, School of MedicineItem Effects of traumatic brain injury and posttraumatic stress disorder on development of Alzheimer's disease in Vietnam Veterans using the Alzheimer's Disease Neuroimaging Initiative: Preliminary report(Elsevier, 2017-06) Weiner, Michael W.; Harvey, Danielle; Hayes, Jacqueline; Landau, Susan M.; Aisen, Paul S.; Petersen, Ronald C.; Tosun, Duygu; Veitch, Dallas P.; Jack, Clifford R., Jr.; Decarli, Charles; Saykin, Andrew J.; Grafman, Jordan; Neylan, Thomas C.; Department of Radiology and Imaging Sciences, IU School of MedicineIntroduction Traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) have previously been reported to be associated with increased risk of Alzheimer's disease (AD). We are using biomarkers to study Vietnam Veterans with/without mild cognitive impairment with a history of at least one TBI and/or ongoing PTSD to determine whether these contribute to the development of AD. Methods Potential subjects identified by Veterans Administration records underwent an initial telephone screen. Consented subjects underwent clinical evaluation, lumbar puncture, structural magnetic resonance imaging, and amyloid positron emission tomography (PET) scans. Results We observed worse cognitive functioning in PTSD and TBI + PTSD groups, worse global cognitive functioning in the PTSD group, lower superior parietal volume in the TBI + PTSD group, and lower amyloid positivity in the PTSD group, but not the TBI group compared to controls without TBI/PTSD. Medial temporal lobe atrophy was not increased in the PTSD and/or TBI groups. Discussion Preliminary results do not indicate that TBI or PTSD increase the risk for AD measured by amyloid PET. Additional recruitment, longitudinal follow-up, and tau-PET scans will provide more information in the future.