Browsing by Subject "Brain injury"
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Item Association Between Early Hyperoxia Exposure After Resuscitation From Cardiac Arrest and Neurological Disability: Prospective Multicenter Protocol-Directed Cohort Study(American Heart Association, 2018-05-15) Roberts, Brian W.; Kilgannon, J. Hope; Hunter, Benton R.; Puskarich, Michael A.; Pierce, Lisa; Donnino, Michael; Leary, Marion; Kline, Jeffrey A.; Jones, Alan E.; Shapiro, Nathan I.; Abella, Benjamin S.; Trzeciak, Stephen; Emergency Medicine, School of MedicineBACKGROUND: Studies examining the association between hyperoxia exposure after resuscitation from cardiac arrest and clinical outcomes have reported conflicting results. Our objective was to test the hypothesis that early postresuscitation hyperoxia is associated with poor neurological outcome. METHODS: This was a multicenter prospective cohort study. We included adult patients with cardiac arrest who were mechanically ventilated and received targeted temperature management after return of spontaneous circulation. We excluded patients with cardiac arrest caused by trauma or sepsis. Per protocol, partial pressure of arterial oxygen (Pao2) was measured at 1 and 6 hours after return of spontaneous circulation. Hyperoxia was defined as a Pao2 >300 mm Hg during the initial 6 hours after return of spontaneous circulation. The primary outcome was poor neurological function at hospital discharge, defined as a modified Rankin Scale score >3. Multivariable generalized linear regression with a log link was used to test the association between Pao2 and poor neurological outcome. To assess whether there was an association between other supranormal Pao2 levels and poor neurological outcome, we used other Pao2 cut points to define hyperoxia (ie, 100, 150, 200, 250, 350, 400 mm Hg). RESULTS: Of the 280 patients included, 105 (38%) had exposure to hyperoxia. Poor neurological function at hospital discharge occurred in 70% of patients in the entire cohort and in 77% versus 65% among patients with versus without exposure to hyperoxia respectively (absolute risk difference, 12%; 95% confidence interval, 1-23). Hyperoxia was independently associated with poor neurological function (relative risk, 1.23; 95% confidence interval, 1.11-1.35). On multivariable analysis, a 1-hour-longer duration of hyperoxia exposure was associated with a 3% increase in risk of poor neurological outcome (relative risk, 1.03; 95% confidence interval, 1.02-1.05). We found that the association with poor neurological outcome began at ≥300 mm Hg. CONCLUSIONS: Early hyperoxia exposure after resuscitation from cardiac arrest was independently associated with poor neurological function at hospital discharge.Item Association Between Proteomic Blood Biomarkers and DTI/NODDI Metrics in Adolescent Football Players: A Pilot Study(Frontiers Media, 2020-11-16) Kawata, Keisuke; Steinfeldt, Jesse A.; Huibregtse, Megan E.; Nowak, Madeleine K.; Macy, Jonathan T.; Kercher, Kyle; Rettke, Devin J.; Shin, Andrea; Chen, Zhongxue; Ejima, Keisuke; Newman, Sharlene D.; Cheng, Hu; Medicine, School of MedicineWhile neuroimaging and blood biomarker have been two of the most active areas of research in the neurotrauma community, these fields rarely intersect to delineate subconcussive brain injury. The aim of the study was to examine the association between diffusion MRI techniques [diffusion tensor imaging (DTI) and neurite orientation/dispersion density imaging (NODDI)] and brain-injury blood biomarker levels [tau, neurofilament-light (NfL), glial-fibrillary-acidic-protein (GFAP)] in high-school football players at their baseline, aiming to detect cumulative neuronal damage from prior seasons. Twenty-five football players were enrolled in the study. MRI measures and blood samples were obtained during preseason data collection. The whole-brain, tract-based spatial statistics was conducted for six diffusion metrics: fractional anisotropy (FA), mean diffusivity (MD), axial/radial diffusivity (AD, RD), neurite density index (NDI), and orientation dispersion index (ODI). Five players were ineligible for MRIs, and three serum samples were excluded due to hemolysis, resulting in 17 completed set of diffusion metrics and blood biomarker levels for association analysis. Our permutation-based regression model revealed that serum tau levels were significantly associated with MD and NDI in various axonal tracts; specifically, elevated serum tau levels correlated to elevated MD (p = 0.0044) and reduced NDI (p = 0.016) in the corpus callosum and surrounding white matter tracts (e.g., longitudinal fasciculus). Additionally, there was a negative association between NfL and ODI in the focal area of the longitudinal fasciculus. Our data suggest that high school football players may develop axonal microstructural abnormality in the corpus callosum and surrounding white matter tracts, such as longitudinal fasciculus. A future study is warranted to determine the longitudinal multimodal relationship in response to repetitive exposure to sports-related head impacts.Item Cerebrospinal fluid biomarkers provide evidence for kidney-brain axis involvement in cerebral malaria pathogenesis(Frontiers Media, 2023-05-02) Conroy, Andrea L.; Datta, Dibyadyuti; Opoka, Robert O.; Batte, Anthony; Bangirana, Paul; Gopinadhan, Adnan; Mellencamp, Kagan A.; Akcan-Arikan, Ayse; Idro, Richard; John, Chandy C.; Pediatrics, School of MedicineIntroduction: Cerebral malaria is one of the most severe manifestations of malaria and is a leading cause of acquired neurodisability in African children. Recent studies suggest acute kidney injury (AKI) is a risk factor for brain injury in cerebral malaria. The present study evaluates potential mechanisms of brain injury in cerebral malaria by evaluating changes in cerebrospinal fluid measures of brain injury with respect to severe malaria complications. Specifically, we attempt to delineate mechanisms of injury focusing on blood-brain-barrier integrity and acute metabolic changes that may underlie kidney-brain crosstalk in severe malaria. Methods: We evaluated 30 cerebrospinal fluid (CSF) markers of inflammation, oxidative stress, and brain injury in 168 Ugandan children aged 18 months to 12 years hospitalized with cerebral malaria. Eligible children were infected with Plasmodium falciparum and had unexplained coma. Acute kidney injury (AKI) on admission was defined using the Kidney Disease: Improving Global Outcomes criteria. We further evaluated blood-brain-barrier integrity and malaria retinopathy, and electrolyte and metabolic complications in serum. Results: The mean age of children was 3.8 years (SD, 1.9) and 40.5% were female. The prevalence of AKI was 46.3% and multi-organ dysfunction was common with 76.2% of children having at least one organ system affected in addition to coma. AKI and elevated blood urea nitrogen, but not other measures of disease severity (severe coma, seizures, jaundice, acidosis), were associated with increases in CSF markers of impaired blood-brain-barrier function, neuronal injury (neuron-specific enolase, tau), excitatory neurotransmission (kynurenine), as well as altered nitric oxide bioavailability and oxidative stress (p < 0.05 after adjustment for multiple testing). Further evaluation of potential mechanisms suggested that AKI may mediate or be associated with CSF changes through blood-brain-barrier disruption (p = 0.0014), ischemic injury seen by indirect ophthalmoscopy (p < 0.05), altered osmolality (p = 0.0006) and through alterations in the amino acids transported into the brain. Conclusion: In children with cerebral malaria, there is evidence of kidney-brain injury with multiple potential pathways identified. These changes were specific to the kidney and not observed in the context of other clinical complications.Item Cortical stimulation for treatment of neurological disorders of hyperexcitability: a role of homeostatic plasticity(Wolters Kluwer, 2019-01) Chai, Zhi; Ma, Cungen; Jin, Xiaoming; Anatomy and Cell Biology, IU School of MedicineHyperexcitability of neural network is a key neurophysiological mechanism in several neurological disorders including epilepsy, neuropathic pain, and tinnitus. Although standard paradigm of pharmacological management of them is to suppress this hyperexcitability, such as having been exemplified by the use of certain antiepileptic drugs, their frequent refractoriness to drug treatment suggests likely different pathophysiological mechanism. Because the pathogenesis in these disorders exhibits a transition from an initial activity loss after injury or sensory deprivation to subsequent hyperexcitability and paroxysmal discharges, this process can be regarded as a process of functional compensation similar to homeostatic plasticity regulation, in which a set level of activity in neural network is maintained after injury-induced activity loss through enhanced network excitability. Enhancing brain activity, such as cortical stimulation that is found to be effective in relieving symptoms of these disorders, may reduce such hyperexcitability through homeostatic plasticity mechanism. Here we review current evidence of homeostatic plasticity in the mechanism of acquired epilepsy, neuropathic pain, and tinnitus and the effects and mechanism of cortical stimulation. Establishing a role of homeostatic plasticity in these disorders may provide a theoretical basis on their pathogenesis as well as guide the development and application of therapeutic approaches through electrically or pharmacologically stimulating brain activity for treating these disorders.Item Depression, Anxiety, and Suicidality in Individuals With Chronic Traumatic Brain Injury Before and During the COVID-19 Pandemic: A National Institute on Disability, Independent Living, and Rehabilitation Research Traumatic Brain Injury Model Systems Study(Elsevier, 2023) Katta-Charles, Sheryl; Adams, Leah M.; Chiaravalloti, Nancy D.; Hammond, Flora M.; Perrin, Paul B.; Rabinowitz, Amanda R.; Venkatesan, Umesh M.; Weintraub, Alan H.; Bombardier, Charles H.; Physical Medicine and Rehabilitation, School of MedicineObjective: To examine the prevalence, severity, and correlates of depression, anxiety, and suicidal ideation in people with traumatic brain injury (TBI) assessed before and during the COVID-19 pandemic. Design: Retrospective cohort study using data collected through the Traumatic Brain Injury Model Systems (TBIMS) network at 1, 2, 5, 10, 15, 20, 25, or 30 years post TBI. Setting: United States-based TBIMS rehabilitation centers with telephone assessment of community residing participants. Participants: Adults (72.4% male; mean age, 47.2 years) who enrolled in the TBIMS National Database and completed mental health questionnaires prepandemic (January 1, 2017 to February 29, 2020; n=5000) or during pandemic (April 1, 2022 to June 30, 2021; n=2009) (N=7009). Interventions: Not applicable. Main outcome measures: Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 questionnaire. Results: Separate linear and logistic regressions were constructed with demographic, psychosocial, injury-related, and functional characteristics, along with a binary indicator of COVID-19 pandemic period (prepandemic vs during pandemic), as predictors of mental health outcomes. No meaningful differences in depression, anxiety, or suicidal ideation were observed before vs during the COVID-19 pandemic. Correlations between predictors and mental health outcomes were similar before and during the pandemic. Conclusions: Contrary to our predictions, the prevalence, severity, and correlates of mental health conditions were similar before and during the COVID-19 pandemic. Results may reflect generalized resilience and are consistent with the most recent findings from the general population that indicate only small, transient increases in psychological distress associated with the pandemic. While unworsened, depression, anxiety, and suicidal ideation remain prevalent and merit focused treatment and research efforts.Item Eletromagnetic Detection of Mild Brain Injury: A Novel Imaging Approach to Post Concussive Syndrome(Scientific Research Publishing, 2021-11) Rizkalla, James; Botros, David; Alqahtani, Nasser; Patnala, Mounica; Salama, Paul; Perez, Felipe Pablo; Rizkalla, Maher; Medicine, School of MedicineIntroduction: Mild traumatic brain injury (mTBI) is a common injury, with nearly 3 - 4 million cases annually in the United States alone. Neuroimaging in patients with mTBI provides little benefit, and is usually not indicated as the diagnosis is primarily clinical. It is theorized that microvascular trauma to the brain may be present in mTBI, that may not be captured by routine MRI and CT scans. Electromagnetic (EM) waves may provide a more sensitive medical imaging modality to provide objective data in the diagnosis of mTBI. Methods: COMSOL simulation software was utilized to mimic the anatomy of the human skull including skin, cranium, cerebrospinal fluid (CSF), gray-matter tissue of the brain, and microvasculature within the neural tissue. The effects of penetrating EM waves were simulated using the finite element analysis software and results were generated to identify feasibility and efficacy. Frequency ranges from 7 GHz to 15 GHz were considered, with 0.6 and 1 W power applied. Results: Variations between the differing frequency levels generated different energy levels within the neural tissue-particularly when comparing normal microvasculature versus hemorrhage from microvasculature. This difference within the neural tissue was subsequently identified, via simulation, serving as a potential imaging modality for future work. Conclusion: The use of electromagnetic imaging of the brain after concussive events may play a role in future mTBI diagnosis. Utilizing the proper depth frequency and wavelength, neural tissue and microvascular trauma may be identified utilizing finite element analysis.Item An Exploratory Study of Endogenous Pain Modulatory Function in Patients Following Mild Traumatic Brain Injury(Oxford University Press, 2019-11-01) Carey, Christopher; Saxe, Jonathan; White, Fletcher A.; Naugle, Kelly M.; Kinesiology, School of Health and Human SciencesBackground: Recent animal research suggests that mild traumatic brain injury (mTBI) facilitates abnormal endogenous modulation of pain, potentially underlying the increased risk for persistent headaches following injury. However, no human studies have directly assessed the functioning of endogenous facilitory and inhibitory systems in the early stages after an mTBI. Objective: The purpose of this exploratory study was to examine trigeminal sensitization and endogenous pain inhibitory capacity in mTBI patients in the acute stage of injury compared with matched controls. We also examined whether post-traumatic headache pain intensity within the mTBI sample was related to sensitization and pain inhibitory capacity. Methods: Twenty-four mTBI patients recruited from emergency departments and 21 age-, race-, and sex-matched controls completed one experimental session. During this session, participants completed quantitative sensory tests measuring trigeminal sensitization (pressure pain thresholds and temporal summation of pain in the head) and endogenous pain inhibition (conditioned pain modulation). Participants also completed validated questionnaires measuring headache pain, depression, anxiety, and pain catastrophizing. Results: The results revealed that the mTBI group exhibited significantly decreased pressure pain thresholds of the head and decreased pain inhibition on the conditioned pain modulation test compared with the control group. Furthermore, correlational analysis showed that the measures of trigeminal sensitization and depression were significantly associated with headache pain intensity within the mTBI group. Conclusions: In conclusion, mTBI patients may be at risk for maladaptive changes to the functioning of endogenous pain modulatory systems following head injury that could increase risk for post-traumatic headaches.Item Incidence and prevalence of coma in the UK and the USA(Oxford University Press, 2022-09-01) Kondziella, Daniel; Amiri, Moshgan; Othman, Marwan H.; Beghi, Ettore; Bodien, Yelena G.; Citerio, Giuseppe; Giacino, Joseph T.; Mayer, Stephan A.; Lawson, Thomas N.; Menon, David K.; Rass, Verena; Sharshar, Tarek; Stevens, Robert D.; Tinti, Lorenzo; Vespa, Paul; McNett, Molly; Venkatasubba Rao, Chethan P.; Helbok, Raimund; Curing Coma Campaign Collaborators; Physical Medicine and Rehabilitation, School of MedicineThe epidemiology of coma is unknown because case ascertainment with traditional methods is difficult. Here, we used crowdsourcing methodology to estimate the incidence and prevalence of coma in the UK and the USA. We recruited UK and US laypeople (aged ≥18 years) who were nationally representative (i.e. matched for age, gender and ethnicity according to census data) of the UK and the USA, respectively, utilizing a crowdsourcing platform. We provided a description of coma and asked survey participants if they-'right now' or 'within the last year'-had a family member in coma. These participants (UK n = 994, USA n = 977) provided data on 30 387 family members (UK n = 14 124, USA n = 16 263). We found more coma cases in the USA (n = 47) than in the UK (n = 20; P = 0.009). We identified one coma case in the UK (0.007%, 95% confidence interval 0.00-0.04%) on the day of the survey and 19 new coma cases (0.13%, 95% confidence interval 0.08-0.21%) within the preceding year, resulting in an annual incidence of 135/100 000 (95% confidence interval 81-210) and a point prevalence of 7 cases per 100 000 population (95% confidence interval 0.18-39.44) in the UK. We identified five cases in the USA (0.031%, 95% confidence interval 0.01-0.07%) on the day of the survey and 42 new cases (0.26%, 95% confidence interval 0.19-0.35%) within the preceding year, resulting in an annual incidence of 258/100 000 (95% confidence interval 186-349) and a point prevalence of 31 cases per 100 000 population (95% confidence interval 9.98-71.73) in the USA. The five most common causes were stroke, medically induced coma, COVID-19, traumatic brain injury and cardiac arrest. To summarize, for the first time, we report incidence and prevalence estimates for coma across diagnosis types and settings in the UK and the USA using crowdsourcing methods. Coma may be more prevalent in the USA than in the UK, which requires further investigation. These data are urgently needed to expand the public health perspective on coma and disorders of consciousness.Item A management algorithm for patients with intracranial pressure monitoring: the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC)(Springer, 2019-12-01) Hawryluk, Gregory W. J.; Aguilera, Sergio; Buki, Andras; Bulger, Eileen; Citerio, Giuseppe; Cooper, D. Jamie; Arrastia, Ramon Diaz; Diringer, Michael; Figaji, Anthony; Gao, Guoyi; Geocadin, Romergryko; Ghajar, Jamshid; Harris, Odette; Hoffer, Alan; Hutchinson, Peter; Joseph, Mathew; Kitagawa, Ryan; Manley, Geoffrey; Mayer, Stephan; Menon, David K.; Meyfroidt, Geert; Michael, Daniel B.; Oddo, Mauro; Okonkwo, David; Patel, Mayur; Robertson, Claudia; Rosenfeld, Jeffrey V.; Rubiano, Andres M.; Sahuquillo, Juan; Servadei, Franco; Shutter, Lori; Stein, Deborah; Stocchetti, Nino; Taccone, Fabio Silvio; Timmons, Shelly; Tsai, Eve; Ullman, Jamie S.; Vespa, Paul; Videtta, Walter; Wright, David W.; Zammit, Christopher; Chesnut, Randall M.; Neurological Surgery, School of MedicineBackground Management algorithms for adult severe traumatic brain injury (sTBI) were omitted in later editions of the Brain Trauma Foundation’s sTBI Management Guidelines, as they were not evidence-based. Methods We used a Delphi-method-based consensus approach to address management of sTBI patients undergoing intracranial pressure (ICP) monitoring. Forty-two experienced, clinically active sTBI specialists from six continents comprised the panel. Eight surveys iterated queries and comments. An in-person meeting included whole- and small-group discussions and blinded voting. Consensus required 80% agreement. We developed heatmaps based on a traffic-light model where panelists’ decision tendencies were the focus of recommendations. Results We provide comprehensive algorithms for ICP-monitor-based adult sTBI management. Consensus established 18 interventions as fundamental and ten treatments not to be used. We provide a three-tier algorithm for treating elevated ICP. Treatments within a tier are considered empirically equivalent. Higher tiers involve higher risk therapies. Tiers 1, 2, and 3 include 10, 4, and 3 interventions, respectively. We include inter-tier considerations, and recommendations for critical neuroworsening to assist the recognition and treatment of declining patients. Novel elements include guidance for autoregulation-based ICP treatment based on MAP Challenge results, and two heatmaps to guide (1) ICP-monitor removal and (2) consideration of sedation holidays for neurological examination. Conclusions Our modern and comprehensive sTBI-management protocol is designed to assist clinicians managing sTBI patients monitored with ICP-monitors alone. Consensus-based (class III evidence), it provides management recommendations based on combined expert opinion. It reflects neither a standard-of-care nor a substitute for thoughtful individualized management.Item Negative Attribution Bias and Related Risk Factors after Brain Injury(Wolters Kluwer, 2021) Neumann, Dawn; Sander, Angelle M.; Perkins, Susan M.; Bhamidipalli, Surya Sruthi; Hammond, Flora M.; Physical Medicine and Rehabilitation, School of MedicineObjective: In participants with traumatic brain injury (TBI) and peer controls, examine (1) differences in negative attributions (interpret ambiguous behaviors negatively); (2) cognitive and emotional factors associated with negative attributions; and (3) negative attribution associations with anger responses, life satisfaction, and participation. Setting: Two TBI outpatient rehabilitation centers. Participants: Participants with complicated mild to severe TBI (n = 105) and peer controls (n = 105). Design: Cross-sectional survey study. Main measures: Hypothetical scenarios describing ambiguous behaviors were used to assess situational anger and attributions of intent, hostility, and blame. Executive functioning, perspective taking, emotion perception and social inference, alexithymia, aggression, anxiety, depression, participation, and life satisfaction were also assessed. Results: Compared with peer controls, participants with TBI rated behaviors significantly more intentional, hostile, and blameworthy. Regression models explained a significant amount of attribution variance (25%-43%). Aggression was a significant predictor in all models; social inference was also a significant predictor of intent and hostility attributions. Negative attributions were associated with anger responses and lower life satisfaction. Conclusion: People with TBI who have higher trait aggression and poor social inferencing skills may be prone to negative interpretations of people's ambiguous actions. Negative attributions and social inferencing skills should be considered when treating anger problems after TBI.