Valerie Mika

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

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.

Combining biochemical and imaging markers to improve diagnosis and characterization of mild traumatic brain injury in the acute setting: results from a pilot study.

Background Mild traumatic brain injury (mTBI) is a significant healthcare burden and its diagnosis remains a challenge in the emergency department. Serum biomarkers and advanced magnetic resonance imaging (MRI) techniques have already demonstrated their potential to improve the detection of brain injury even in patients with negative computed tomography (CT) findings. The objective of this study was to determine the clinical value of a combinational use of both blood biomarkers and MRI in mTBI detection and their characterization in the acute setting (within 24 hours after injury). Methods Nine patients with mTBI were prospectively recruited from the emergency department. Serum samples were collected at the time of hospital admission and every 6 hours up to 24 hours post injury. Neuronal (Ubiquitin C-terminal Hydrolase-L1 [UCH-L1]) and glial (glial fibrillary acidic protein [GFAP]) biomarker levels were analyzed. Advanced MRI data were acquired at 9±6.91 hours after injury. Patients’ neurocognitive status was assessed by using the Standard Assessment of Concussion (SAC) instrument. Results The median serum levels of UCH-L1 and GFAP on admission were increased 4.9 folds and 10.6 folds, respectively, compared to reference values. Three patients were found to have intracranial hemorrhages on SWI, all of whom had very high GFAP levels. Total volume of brain white matter (WM) with abnormal fractional anisotropy (FA) measures of diffusion tensor imaging (DTI) were negatively correlated with patients’ SAC scores, including delayed recall. Both increased and decreased DTI-FA values were observed in the same subjects. Serum biomarker level was not correlated with patients’ DTI data nor SAC score. Conclusions Blood biomarkers and advanced MRI may correlate or complement each other in different aspects of mTBI detection and characterization. GFAP might have potential to serve as a clinical screening tool for intracranial bleeding. UCH-L1 complements MRI in injury detection. Impairment at WM tracts may account for the patients’ neurocognitive symptoms.

Cerebral Hemodynamic Changes of Mild Traumatic Brain Injury at the Acute Stage

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.

Comparison of quantitative EEG to current clinical decision rules for head CT use in acute mild traumatic brain injury in the ED

STUDY OBJECTIVE We compared the performance of a handheld quantitative electroencephalogram (QEEG) acquisition device to New Orleans Criteria (NOC), Canadian CT Head Rule (CCHR), and National Emergency X-Radiography Utilization Study II (NEXUS II) Rule in predicting intracranial lesions on head computed tomography (CT) in acute mild traumatic brain injury in the emergency department (ED). METHODS Patients between 18 and 80 years of age who presented to the ED with acute blunt head trauma were enrolled in this prospective observational study at 2 urban academic EDs in Detroit, MI. Data were collected for 10 minutes from frontal leads to determine a QEEG discriminant score that could maximally classify intracranial lesions on head CT. RESULTS One hundred fifty-two patients were enrolled from July 2012 to February 2013. A total 17.1% had acute traumatic intracranial lesions on head CT. Quantitative electroencephalogram discriminant score of greater than or equal to 31 was found to be a good cutoff (area under receiver operating characteristic curve = 0.84; 95% confidence interval [CI], 0.76-0.93) to classify patients with positive head CT. The sensitivity of QEEG discriminant score was 92.3 (95% CI, 73.4-98.6), whereas the specificity was 57.1 (95% CI, 48.0-65.8). The sensitivity and specificity of the decision rules were as follows: NOC 96.1 (95% CI, 78.4-99.7) and 15.8 (95% CI, 10.1-23.6); CCHR 46.1 (95% CI, 27.1-66.2) and 86.5 (95% CI, 78.9-91.7); NEXUS II 96.1 (95% CI, 78.4-99.7) and 31.7 (95% CI, 23.9-40.7). CONCLUSION At a sensitivity of greater than 90%, QEEG discriminant score had better specificity than NOC and NEXUS II. Only CCHR had better specificity than QEEG discriminant score but at the cost of low (<50%) sensitivity.

The Role of Neck Muscle Activities on the Risk of Mild Traumatic Brain Injury in American Football.

Concussion, or mild traumatic brain injury (mTBI), is frequently associated with sports activities. It has generally been accepted that neck strengthening exercises are effective as a preventive strategy for reducing sports-related concussion risks. However, the interpretation of the link between neck strength and concussion risks remains unclear. In this study, a typical helmeted head-to-head impact in American football was simulated using the head and neck complex finite element (FE) model. The impact scenario selected was previously reported in lab-controlled incident reconstructions from high-speed video footages of the National Football League using two head-neck complexes taken from Hybrid III dummies. Four different muscle activation strategies were designed to represent no muscle response, a reactive muscle response, a pre-activation response, and response due to stronger muscle strength. Head kinematics and various head/brain injury risk predictors were selected as response variables to compare the effects of neck muscles on the risk of sustaining the concussion. Simulation results indicated that active responses of neck muscles could effectively reduce the risk of brain injury. Also, anticipatory muscle activation played a dominant role on impact outcomes. Increased neck strength can decrease the time to compress the neck and its effects on reducing brain injury risks need to be further studied.

Utility of point of care assessment of platelet reactivity (using the PFA-100®) to aid in diagnosis of stroke

Background: Rapid and accurate diagnosis of patients presenting with symptoms of stroke is needed to facilitate the timely delivery of proven effective treatment for patients with acute ischemic stroke (AIS). The aim of this study was to determine whether early assessment of platelet reactivity in patients presenting with symptoms of AIS was associated with a diagnosis of AIS, transient ischemic attack (TIA), or stroke mimic. Methods: This prospective study included patients with symptoms of AIS treated at an inner‐city emergency department (ED). Blood samples were obtained and assayed for platelet reactivity (quantified by closure time). Patients were grouped by discharge diagnosis into: AIS, TIA, or stroke mimic. Binary logistic regression model was used to predict the association of closure time with the final diagnosis of 1) either AIS or TIA or, 2) stroke mimic. Results: Of 114 patients enrolled, 32 were diagnosed with AIS, 33 TIA, and 49 were diagnosed as a stroke mimic. There was no significant difference in closure times among patients with a diagnosis of AIS or TIA versus stroke mimic. A history of migraines and history of seizures were independently associated with lower odds of an AIS or TIA diagnosis (OR 0.31, 95% CI 0.10 to 0.94 and OR 0.08, 95% CI 0.01 to 0.88, respectively). Conclusion: Closure time was not found to be a clinically reliable differentiator of patients with a diagnosis of AIS, TIA, or stroke mimic in the ED.

Emergency department visits in patients with low acuity conditions: Factors associated with resource utilization.

Objectives: To identify health beliefs of emergency department (ED) patients with low acuity conditions and how these affect ambulance (AMB) utilization. Methods: We performed a prospective, observational study on a convenience sample of patients 18 years or older, who presented to the ED of an urban, academic hospital with an Emergency Severity Index (ESI) triage level of 4 or 5. Demographics, treatment, and disposition data were obtained along with self‐administered surveys. Characteristics of patients with low acuity conditions who presented to the ED by AMB were compared to the patients who came to the ED by private transportation (PT). Data were analyzed with the chi‐square test, t‐test, and Mann‐Whitney test. Results: A total of 197 patients (97 AMB and 100 PT) were enrolled. Compared to PT, AMB patients were more likely to: be insured (82% vs. 56%; p = 0.000), have a primary care provider (62% vs. 44%; p = 0.048), and lack a regular means of transportation (53% vs. 33%; p = 0.005). Three surveys were used the SF‐8, Short Test of Functional Health Literacy in Adults [STOFHLA], and Health Belief Model [HBM]. Answers to HBM showed patients perceive that their illness required care within one hour of arrival (38% vs. 21%; p = 0.04), have used an ambulance in the past year (76% vs. 33%; p = 0.001) and to utilize an ambulance in the future for similar concerns (53% vs. 15%; p = 0.000). AMB patients were more likely to call an ambulance for any health concern (p = 0.035) and felt that there were enough ambulances for all patients in the city (p = 0.01). There were no differences in age, employment, level of income and education, nor hospital admission rate between groups. Conclusions: Ambulance use in low‐acuity ED patients is associated with misperceptions regarding severity of illness and resource allocation as well as limited access to private transportation. Understanding patient perceptions of illness and other barriers to receiving care is imperative for the development of interventions aimed at enabling change in health behaviors such as the elective use of limited resources.