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Intracerebral hemorrhage (ICH) is a devastating type of stroke that lacks a specific treatment. An intense immune response develops after ICH, which contributes to neuronal injury, disability, and death. However, the specific mediators of inflammation-induced injury remain unclear. The objective of the present study was to determine whether blood-derived CCR2 ϩ Ly6Chi inflammatory monocytes contribute to disability. ICH was induced in mice and the resulting inflammatory response was quantified using flow cytometry, confocal microscopy, and neurobehavioral testing. Importantly, blood-derived monocytes were distinguished from resident microglia by differential CD45 staining and by using bone marrow chimeras with fluorescent leukocytes. After ICH, blood-derived CCR2 ϩ Ly6Chi inflammatory monocytes trafficked into the brain, outnumbered other leukocytes, and produced tumor necrosis factor. Ccr2 Ϫ/Ϫ mice, which have few circulating inflammatory monocytes, exhibited better motor function following ICH than control mice. Chimeric mice with wild-type CNS cells and Ccr2 Ϫ/Ϫ hematopoietic cells also exhibited early improvement in motor function, as did wild-type mice after inflammatory monocyte depletion. These findings suggest that blood-derived inflammatory monocytes contribute to acute neurological disability. To determine the translational relevance of our experimental findings, we examined CCL2, the principle ligand for the CCR2 receptor, in ICH patients. Serum samples from 85 patients were collected prospectively at two hospitals. In patients, higher CCL2 levels at 24 h were independently associated with poor functional outcome at day 7 after adjusting for potential confounding variables. Together, these findings suggest that inflammatory monocytes worsen early disability after murine ICH and may represent a therapeutic target for patients.

Background Injury is a major contributor to morbidity and mortality in the United States. Accordingly, expanding access to trauma care is a Healthy People priority. The extent to which disparities in access to trauma care exist in the US is unknown. Our objective was to describe geographic, demographic, and socioeconomic disparities in access to trauma care in the United States. Methods Cross-sectional study of the US population in 2010 using small units of geographic analysis and validated estimates of population access to a Level I or II trauma center within 60 minutes via ambulance or helicopter. We examined the association between geographic, demographic, and socioeconomic factors and trauma center access, with subgroup analyses of urban-rural disparities. Results Of the 309 million people in the US in 2010, 29.7 million lacked access to trauma care. Across the country, areas with higher income were significantly more likely to have access (OR 1.30, 95% CI 1.12–1.50), as were major cities (OR 2.13, 95% CI 1.25–3.62) and suburbs (OR 1.27, 95% CI 1.02–1.57). Areas with higher rates of uninsured (OR 0.09, 95% CI 0.07–0.11) and Medicaid or Medicare eligible patients (OR 0.69, 95% CI 0.59–0.82) were less likely to have access. Areas with higher proportions of blacks and non-whites were more likely to have access (OR 1.37, 95% CI 1.19–1.58), as were areas with higher proportions of Hispanics and foreign-born persons (OR 1.51, 95% CI 1.13–2.01). Overall, rurality was associated with significantly lower access to trauma care (OR 0.20, 95% CI 0.18–0.23). Conclusion While the majority of the United States has access to trauma care within an hour, almost 30 million US residents do not. Significant disparities in access were evident for vulnerable populations defined by insurance status, income, and rurality.

Abstract:We introduce, validate and demonstrate a new software correlator for high-speed measurement of blood flow in deep tissues based on diffuse correlation spectroscopy (DCS). The software correlator scheme employs standard PC-based data acquisition boards to measure temporal intensity autocorrelation functions continuously at 50 − 100 Hz, the fastest blood flow measurements reported with DCS to date. The data streams, obtained in vivo for typical source-detector separations of 2.5 cm, easily resolve pulsatile heart-beat fluctuations in blood flow which were previously considered to be noise. We employ the device to separate tissue blood flow from tissue absorption/scattering dynamics and thereby show that the origin of the pulsatile DCS signal is primarily flow, and we monitor cerebral autoregulation dynamics in healthy volunteers more accurately than with traditional instrumentation as a result of increased data acquisition rates. Finally, we characterize measurement signal-to-noise ratio and identify count rate and averaging parameters needed for optimal performance. References and links 1. D. A. Boas, L. E. Campbell, and A. G. Yodh, "Scattering and imaging with diffusing temporal field correlations," Phy. Rev. Lett. 75, 1855Lett. 75, -1858Lett. 75, (1995

Background and Purpose-Occult paroxysmal atrial fibrillation (AF) is found in a substantial minority of patients with cryptogenic stroke. Identifying reliable predictors of paroxysmal AF after cryptogenic stroke would allow clinicians to more effectively use outpatient cardiac monitoring and ultimately reduce secondary stroke burden. Methods-We analyzed a retrospective cohort of consecutive patients who underwent 28-day mobile cardiac outpatient telemetry after cryptogenic stroke or transient ischemic stroke. Univariate and multivariable analyses were performed to identify clinical, echocardiographic, and radiographic features associated with the detection of paroxysmal AF. Results-Of 227 patients with cryptogenic stroke (179) or transient ischemic stroke (48), 14% (95% confidence interval, 9%-18%) had AF detected on mobile cardiac outpatient telemetry, 58% of which was ≥30 seconds in duration. Age >60 years (odds ratio, 3.7; 95% confidence interval, 1.3-11) and prior cortical or cerebellar infarction seen on neuroimaging (odds ratio, 3.0; 95% confidence interval, 1.2-7.6) were independent predictors of AF. AF was detected in 33% of patients with both factors, but only 4% of patients with neither. No other clinical features (including demographics, CHA 2 DS 2 -VASc [combined stroke risk score: congestive heart failure, hypertension, age, diabetes, prior stroke/transient ischemic attack, vascular disease, sex] score, or stroke symptoms), echocardiographic findings (including left atrial size or ejection fraction), or radiographic characteristics of the acute infarction (including location, topology, or number) were associated with AF detection. Conclusions-Mobile cardiac outpatient telemetry detects AF in a substantial proportion of cryptogenic stroke patients. Age >60 years and radiographic evidence of prior cortical or cerebellar infarction are robust indicators of occult AF. Patients with neither had a low prevalence of AF.

Background and Purpose A primary goal of acute ischemic stroke (AIS) management is to maximize perfusion in the affected region and surrounding ischemic penumbra. However, interventions to maximize perfusion, such as flat head-of-bed (HOB) positioning, are currently prescribed empirically. Bedside monitoring of cerebral blood flow (CBF) allows the effects of interventions such as flat HOB to be monitored, and may ultimately be used to guide clinical management. Methods Cerebral perfusion was measured during head of bed (HOB) manipulations in 17 patients with unilateral acute ischemic stroke affecting large cortical territories in the anterior circulation. Simultaneous measurements of frontal CBF and arterial flow velocity were performed with diffuse correlation spectroscopy (DCS) and transcranial Doppler ultrasound, respectively. Results were analyzed in the context of available clinical data and a previous study. Results Frontal CBF, averaged over the patient cohort, decreased by 17% (p=0.034) and 15% (p=0.011) in the ipsilesional and contralesional hemispheres, respectively, when HOB was changed from flat to 30°. Significant (cohort-averaged) changes in blood velocity were not observed. Individually, varying responses to HOB manipulation were observed, including paradoxical increases in CBF with increasing HOB angle. Clinical features, stroke volume, and distance to the optical probe could not explain this paradoxical response. Conclusions A lower HOB angle results in an increase in cortical CBF without a significant change in arterial flow velocity in AIS, but there is variability across patients in this response. Bedside CBF monitoring with DCS provides a potential means to individualize interventions designed to optimize CBF in AIS.

Geographic disparities in tPA use for AIS are increasing. Greater understanding of the effectors of tPA utilization is necessary to ensure that access to tPA treatment is equitable for all communities in the United States.

Background Previous research has indicated that women and Blacks have worse outcomes following acute ischemic stroke (AIS). Little research has been done to investigate the combined influence of race and gender in the presentation, treatment and outcome of patients with AIS. We sought to determine the association of race and gender on initial stroke severity, thrombolysis and functional outcome after AIS. Methods AIS patients who presented to two academic medical centers in the United States (2004-2011) were identified through prospective registries. In-hospital strokes were excluded. Stroke severity, measured by admission National Institutes of Health Stroke Scale (NIHSS) scores, treatment with tissue plasminogen activator (tPA), neurologic deterioration (defined by a ≥2 point increase in NIHSS), and functional outcome at discharge, measured by the modified Rankin Scale (mRS), were investigated. These outcomes were compared across race/gender groups. A sub-analysis was conducted to assess race/gender differences in exclusion criteria for tPA. Results Of the 4925 patients included in this study, 2346 (47.6%) were women and 2310 (46.9%) were black. White women had the highest median NIHSS on admission (8) with White men had the lowest median NIHSS on admission (6). There were no differences in outcomes between Black men and White men. A smaller percentage of Black women than White women were treated with tPA (27.6% vs. 36.6%, p<0.0001), partially due to a greater proportion of White women presenting within 3 hours (51% vs. 45.5%, p =0.0005). Black women had decreased odds of poor functional outcome relative to White women (OR=0.85, 95%CI 0.72-1.00), but after adjustment for baseline differences in age, NIHSS and tPA use this association was no longer significant (OR=1.2, 95%CI 0.92-1.46, p=0.22). Black women with a NIHSS on admission of less than 7 were at lower odds of receiving tPA than the other race gender groups, even after adjusting for arriving within 3 hours and admission glucose (OR 0.66, 95%CI 0.44-0.99, p=0.0433). Conclusion Race and gender were not significantly associated with short-term outcome, although Black women were significantly less likely to be treated with tPA. Black women had more tPA exclusions than any other group. The primary reason for tPA exclusion in this study was not arriving within 3 hours of stroke symptom onset. Given the growth in incident strokes projected in minority groups in the next 4 decades, identifying factors that contribute to Black women not arriving to the ED in time is of great importance.