Infarct density defined by ADC threshold is associated with long-term functional outcome after endovascular thrombectomy.

OBJECTIVES: Endovascular thrombectomy (EVT) dramatically improves clinical outcomes, but the reduction in final infarct volume only accounts for 10-15% of the treatment benefit. We aimed to develop a novel MRI-ADC-based metric that quantify the degree of tissue injury to test the hypothesis that it outperforms infarct volume in predicting long-term outcome. MATERIALS AND METHODS: A single-center cohort consisted of consecutive acute stroke patients with anterior circulation large vessel occlusion, successful recanalization via EVT (mTICI ≥2b), and MRI of the brain between 12 hours and 7 days post-EVT. Imaging was processed via RAPID software. Final infarct volume was based on the traditional ADC <620 threshold. Logistic regression quantified the association of lesion volumes and good outcome (90-day modified Rankin Scale ≤2) at a range of lower ADC thresholds (<570, <520, and <470). Infarct density was calculated as the percentage of the final infarct volume below the ADC threshold with the greatest effect size. Univariate and multivariate logistic regression quantified the association between imaging/clinical metrics and functional outcome. RESULTS: 120 patients underwent MRI after successful EVT. Lesion volume based on the ADC threshold <470 had the strongest association with good outcome (OR: 0.81 per 10mL; 95% CI: 0.66-0.99). In a multivariate model, infarct density (<470/<620 * 100) was independently associated with good outcome (aOR 0.68 per 10%; 95% CI: 0.49-0.95), but final infarct volume was not (aOR 0.98 per 10mL; 95% CI: 0.85-1.14). CONCLUSIONS: Infarct density after EVT is more strongly associated with long-term clinical outcome than infarct volume.

Validation of the Openwater wearable optical system: cerebral hemodynamic monitoring during a breath-hold maneuver.

Significance: Bedside cerebral blood flow (CBF) monitoring has the potential to inform and improve care for acute neurologic diseases, but technical challenges limit the use of existing techniques in clinical practice. Aim: Here, we validate the Openwater optical system, a novel wearable headset that uses laser speckle contrast to monitor microvascular hemodynamics. Approach: We monitored 25 healthy adults with the Openwater system and concurrent transcranial Doppler (TCD) while performing a breath-hold maneuver to increase CBF. Relative blood flow (rBF) was derived from changes in speckle contrast, and relative blood volume (rBV) was derived from changes in speckle average intensity. Results: A strong correlation was observed between beat-to-beat optical rBF and TCD-measured cerebral blood flow velocity (CBFv), R=0.79; the slope of the linear fit indicates good agreement, 0.87 (95% CI: 0.83 -0.92). Beat-to-beat rBV and CBFv were also strongly correlated, R=0.72, but as expected the two variables were not proportional; changes in rBV were smaller than CBFv changes, with linear fit slope of 0.18 (95% CI: 0.17 to 0.19). Further, strong agreement was found between rBF and CBFv waveform morphology and related metrics. Conclusions: This first in vivo validation of the Openwater optical system highlights its potential as a cerebral hemodynamic monitor, but additional validation is needed in disease states.

Evaluating the Morphology of Unique Superficial Fissured Cartilage Lesions at the Femoral Head-Neck Junction in Patients with Femoroacetabular Impingement Syndrome.

Background: While an association between femoroacetabular impingement (FAI) and osteoarthritis (OA) has been reported, the mechanistic differences and transition between the 2 conditions is not fully understood. In FAI, cartilage lesions at the femoral head-neck junction can sometimes be visualized during hip arthroscopy. Purpose/Hypothesis: The purpose of this study was to describe a unique dimpled pattern of superficial fissured cartilage lesions on the femoral head-neck junction at impingement site in patients with FAI syndrome (FAIS) and to evaluate the clinical, histological, and genetic phenotype of this cartilage. We hypothesized that the cartilage lesions may indicate risk for, or predict occurrence of, OA. Study Design: Controlled laboratory study. Methods: Six hips (6 patients; mean age, 34.2 ± 12.9 years; range, 19-54 years) with dimpled or fissured cartilage were included among patients who underwent hip arthroscopy for treatment of FAIS from October 2020 through December 2021. This affected cartilage (dimple-pattern group) and normal cartilage (control group) on the femoral head-neck junction were collected from the same patients and evaluated for histological quantification by Mankin scores and expression of proteins related to cartilage degeneration (eg, matrix metalloproteinase [MMP]-1, MMP-2, MMP-3, MMP-10, and MMP-12, tissue inhibitor of metalloproteinase [TIMP]-1 and TMP-2, aggrecan neopepitope CS846, and hyaluronic acid [HA]) with the use of Milliplex Multiplex Assays. Results: All 6 hips were of the mixed FAI subtype. Preoperatively, 4 of 6 hips had Tönnis grade 1 radiographic changes, which was associated with greater femoral head chondral damage visualized intraoperatively. Mankin scores for the normal cartilage group and the dimple-pattern group were 0.67 ± 0.82 and 3.3 ± 0.82, respectively. Dimple pattern fissured cartilage showed a significant increase in Mankin score (P = .031) and a significant increase in protein expression of CS846 (P = .031) compared with normal cartilage. There were no significant differences in MMPs, TIMPs, or HA levels between the 2 groups. Conclusion: The dimple pattern fissured cartilage, compared to normal cartilage, showed histologically significant cartilage degeneration and a significant increase in protein expression of CS846, a biomarker for early OA. Clinical Relevance: This lesion serves as helpful visual indicator of early degeneration of the cartilage of femoral head-neck junction caused by FAIS.

Hospital-Level Variability in Reporting of Ischemic Stroke Subtypes and Supporting Diagnostic Evaluation in GWTG-Stroke Registry.

BACKGROUND: Secondary prevention of ischemic stroke (IS) requires adequate diagnostic evaluation to identify the likely etiologic subtype. We describe hospital-level variability in diagnostic testing and IS subtyping in a large nationwide registry. METHODS AND RESULTS: We used the GWTG-Stroke (Get With The Guidelines-Stroke) registry to identify patients hospitalized with a diagnosis of acute IS at 1906 hospitals between January 1, 2016, and September 30, 2017. We compared the documentation rates and presence of risk factors, diagnostic testing, achievement/quality measures, and outcomes between patients with and without reported IS subtype. Recording of diagnostic evaluation was optional in all IS subtypes except cryptogenic, where it was required. Of 607 563 patients with IS, etiologic IS subtype was documented in 57.4% and missing in 42.6%. Both the rate of missing stroke pathogenesis and the proportion of cryptogenic strokes were highly variable across hospitals. Patients missing stroke pathogenesis less frequently had documentation of risk factors, evidence-based interventions, or discharge to home. The reported rates of major diagnostic testing, including echocardiography, carotid and intracranial vascular imaging, and short-term cardiac monitoring were <50% in patients with documented IS pathogenesis, although these variables were missing in >40% of patients. Long-term cardiac rhythm monitoring was rarely reported, even in cryptogenic stroke. CONCLUSIONS: Reporting of IS etiologic subtype and supporting diagnostic testing was low overall, with high rates of missing optional data. Improvement in the capture of these data elements is needed to identify opportunities for quality improvement in the diagnostic evaluation and secondary prevention of stroke.

Validation of the Openwater wearable optical system: cerebral hemodynamic monitoring during a breath hold maneuver.

Bedside cerebral blood flow (CBF) monitoring has the potential to inform and improve care for acute neurologic diseases, but technical challenges limit the use of existing techniques in clinical practice. Here we validate the Openwater optical system, a novel wearable headset that uses laser speckle contrast to monitor microvascular hemodynamics. We monitored 25 healthy adults with the Openwater system and concurrent transcranial Doppler (TCD) while performing a breath-hold maneuver to increase CBF. Relative blood flow (rBF) was derived from the changes in speckle contrast, and relative blood volume (rBV) was derived from the changes in speckle average intensity. A strong correlation was observed between beat-to-beat optical rBF and TCD-measured cerebral blood flow velocity (CBFv), R=0.79; the slope of the linear fit indicates good agreement, 0.87 (95% CI:0.83-0.92). Beat-to-beat rBV and CBFv were strongly correlated, R=0.72, but as expected the two variables were not proportional; changes in rBV were smaller than CBFv changes, with linear fit slope of 0.18 (95% CI:0.17-0.19). Further, strong agreement was found between rBF and CBFv waveform morphology and related metrics. This first in vivo validation of the Openwater optical system highlights its potential as a cerebral hemodynamic monitor, but additional validation is needed in disease states.

Differential thrombectomy utilization across hospital classifications in the United States.

OBJECTIVES: To determine hospital-level factors associated with thrombectomy uptake. MATERIALS AND METHODS: The Nationwide Emergency Department Sample was retrospectively queried to determine the total number of thrombectomies performed based on different hospital characteristics. Joint point analysis was used to determine which years were associated with significant increases in the number of high-volume thrombectomy centers (ostensibly defined as >50 thrombectomies/year), thrombectomy-capable centers (>15 thrombectomies/year), and total number of thrombectomies performed. Multivariable logistic regression was used to determine hospital factors associated with having an increased odds of performing thrombectomies, and of being classified as a high-volume thrombectomy or a thrombectomy-capable center. RESULTS: Between 2007-2020 there was a stepwise increase in the number of thrombectomy-capable and high-volume thrombectomy centers in the United States. In 2020, there were a total of 15,705 thrombectomies performed, with 89 high-volume thrombectomy centers, and 359 thrombectomy-capable centers. The number of thrombectomy-capable centers significantly increased after 2011. After 2013 and 2016 there was a significant change in the growth rate of high-volume thrombectomy centers. There was also a significant increase in the total number of thrombectomies performed after 2016. Hospital characteristics that were associated with an increased likelihood of being classified as thrombectomy-capable or high-volume included trauma level 1 and 2 hospitals. CONCLUSIONS: Between 2007 and 2020, there was a marked growth in thrombectomy utilization for acute ischemic stroke. This growth outpaced new diagnoses of ischemic stroke, and was driven largely by certain hospital types, with the greatest rises following seminal publications of positive randomized thrombectomy trials.

A Shorter Door-In-Door-Out Time Is Associated with Improved Outcome in Large Vessel Occlusion Stroke.

Introduction: Endovascular thrombectomy (EVT) significantly improves outcomes in large vessel occlusion stroke (LVOS). When a patient with a LVOS arrives at a hospital that does not perform EVT, emergent transfer to an endovascular stroke center (ESC) is required. Our objective was to determine the association between door-in-door-out time (DIDO) and 90-day outcomes in patients undergoing EVT. Methods: We conducted an analysis of the Optimizing Prehospital Stroke Systems of Care-Reacting to Changing Paradigms (OPUS-REACH) registry of 2,400 LVOS patients treated at nine ESCs in the United States. We examined the association between DIDO times and 90-day outcomes as measured by the modified Rankin scale. Results: A total of 435 patients were included in the final analysis. The mean DIDO time for patients with good outcomes was 17 minute shorter than patients with poor outcomes (122 minutes [min] vs 139 min, P = 0.04). Absolute DIDO cutoff times of ≤60 min, ≤90 min, or ≤120 min were not associated with improved functional outcomes (46.4 vs 32.3%, P = 0.12; 38.6 vs 30.6%, P = 0.10; and 36.4 vs 28.9%, P = 0.10, respectively). This held true for patients with hyperacute strokes of less than four-hour onset. Lower baseline National Institutes of Health Stroke Scale (NIHSS) score (11.9 vs 18.2, P = <.001) and younger age (62.5 vs 74.9 years (P < .001) were associated with improved outcomes. On multiple regression analysis, age (odds ratio [OR] 1.71, 95% confidence interval [CI] 1.45-2.02) and baseline NIHSS score (OR 1.67, 95% CI 1.42-1.98) were associated with improved outcomes while DIDO time was not associated with better outcome (OR 1.13, 95% CI 0.99-1.30). Conclusion: Although the DIDO time was shorter for patients with a good outcome, this was non-significant in multiple regression analysis. Receipt of intravenous thrombolysis and time to EVT were not associated with better outcomes, while male gender, lower age, arrival by private vehicle, and lower NIHSS score portended better outcomes. No absolute DIDO-time cutoff or modifiable factor was associated with improved outcomes for LVOS. This study underscores the need to streamline DIDO times but not to set an artificial DIDO time benchmark to meet.

Delay in hospital presentation is the main reason large vessel occlusion stroke patients do not receive intravenous thrombolysi.

Objectives: Intravenous thrombolysis (IVT) and endovascular therapy (EVT) are the mainstays of treatment for large vessel occlusion stroke (LVOS). Prior studies have examined why patients have not received IVT, the most cited reasons being last-known-well (LKW) to hospital arrival of >4.5 hours and minor/resolving stroke symptoms. Given that LVOS patients typically present moderate-to-severe neurologic deficits, these patients should be easier to identify and treat than patients with minor strokes. This investigation explores why IVT was not administered to a cohort of LVOS patients who underwent EVT. Methods: This is an analysis of the Optimizing the Use of Prehospital Stroke Systems of Care (OPUS-REACH) registry, which contains patients from 9 endovascular centers who underwent EVT between 2015 and 2020. The exposure of interest was the receipt of intravenous thrombolysis. Descriptive summary statistics are presented as means and SDs for continuous variables and as frequencies with percentages for categorical variables. Two-sample t tests were used to compare continuous variables and the chi-square test was used to compare categorical variables between those who received IVT and those who did not receive EVT. Results: Two thousand forty-three patients were included and 60% did not receive IVT. The most common reason for withholding IVT was LKW to arrival of >4.5 (57.2%). The second most common contraindication was oral anticoagulation (15.5%). On multivariable analysis, 2 factors were associated with not receiving IVT: increasing age (odds ratio [OR] 0.86; 95% confidence interval [CI] 0.78-0.93) and increasing time from LKW-to hospital arrival (OR 0.45 95% CI 0.46-0.49). Conclusion: Like prior studies, the most frequent reason for exclusion from IVT was a LKW to hospital presentation of >4.5 hours; the second reason was anticoagulation. Efforts must be made to increase awareness of the time-sensitive nature of IVT and evaluate the safety of IVT in patients on oral anticoagulants.

Randomized Trial of a Social Support Intervention to Improve Home Blood Pressure Monitoring in Patients With Cerebrovascular Disease.

BACKGROUND: A pilot randomized trial evaluating whether a social support intervention improves adherence to home blood pressure (BP) monitoring among patients with cerebrovascular disease. METHODS: Subjects with ischemic stroke, intracerebral hemorrhage, or transient ischemic attack within 5 years with BP >140/90, were given a centrally monitored home BP cuff and asked to check their BP twice a day for 90 ± 7 days. Subjects received text and/or email reminders for missed measurements and weekly reports on adherence/BP control. Subjects were randomized 1:1 to a social support intervention, in which close personal contact also received all study-related education and communications. The primary outcome was the proportion of requested measurements completed. A secondary outcome was a change in BP over time. RESULTS: Thirty-three subjects were enrolled, 15 in the control arm and 18 in the social support arm. The social support arm completed a greater proportion of BP measurements at day 30 (88% vs 78%), day 60 (72% vs 54%), and day 83 (60% vs 40%), but none of these differences were statistically significant ( P > 0.05). Comparing the first 7 days of BP readings to the last 7 days across subjects, there was a nonsignificant decrease in BP over time (systolic BP = -2.8 mm Hg, P = 0.29 and diastolic BP = -1.7, P = 0.36). The social support intervention did not modify the change in BP over time. CONCLUSION: A social support intervention may increase adherence to home BP monitoring. This pilot study provides important preliminary data to inform the design of larger more definitive trials utilizing self-monitoring of BP in patients with cerebrovascular disease.

Factors associated with door-in-door-out times in large vessel occlusion stroke patients undergoing endovascular therapy.

INTRODUCTION: In the management of large vessel occlusion stroke (LVOS), patients are frequently evaluated first at a non-endovascular stroke center and later transferred to an endovascular stroke center (ESC) for endovascular treatment (EVT). The door-in-door-out time (DIDO) is frequently used as a benchmark for transferring hospitals though there is no universally accepted nor evidenced-based DIDO time. The goal of this study was to identify factors affecting DIDO times in LVOS patients who ultimately underwent EVT. METHODS: The Optimizing Prehospital Use of Stroke Systems of Care-Reacting to Changing Paradigms (OPUS-REACH) registry is comprised of all LVOS patients who underwent EVT at one of nine endovascular centers in the Northeast United States between 2015 and 2020. We queried the registry for all patients who were transferred from a non-ESC to one of the nine ESCs for EVT. Univariate analysis was performed using t-tests to obtain a p value. A priori, we defined a p value of <0.05 as significant. Multiple logistic regression was conducted to determine the association of variables to estimate an odds ratio. RESULTS: 511 patients were included in the final analysis. The mean DIDO times for all patients was 137.8 min. Vascular imaging and treatment at a non-certified stroke center were associated with longer DIDO times by 23 and 14 min, respectively. On multivariate analyses, the acquisition of vascular imaging was associated with 16 additional minutes spent at the non-ESC while presentation to a non-stroke certified hospital was associated with 20 additional minutes spent at the transferring hospital. The administration of intravenous thrombolysis (IVT) was associated with 15 min less spent at the non-ESC. DISCUSSION: Vascular imaging and non-stroke certified stroke centers were associated with longer DIDO times. Non-ESCs should integrate vascular imaging into their workflow as feasible to reduce DIDO times. Further work examining other details regarding the transfer process such as transfer via ground or air, could help further identify opportunities to improve DIDO times.

Dynamic cerebral autoregulation measured by diffuse correlation spectroscopy.

Dynamic cerebral autoregulation (dCA) can be derived from spontaneous oscillations in arterial blood pressure (ABP) and cerebral blood flow (CBF). Transcranial Doppler (TCD) measures CBF-velocity and is commonly used to assess dCA. Diffuse correlation spectroscopy (DCS) is a promising optical technique for non-invasive CBF monitoring, so here we aimed to validate DCS as a tool for quantifying dCA. In 33 healthy adults and 17 acute ischemic stroke patients, resting-state hemodynamic were monitored simultaneously with high-speed (20 Hz) DCS and TCD. dCA parameters were calcaulated by a transfer function analysis using a Fourier decomposition of ABP and CBF (or CBF-velocity). Strong correlation was found between DCS and TCD measured gain (magnitude of regulation) in healthy volunteers (r = 0.73, p < 0.001) and stroke patients (r = 0.76, p = 0.003). DCS-gain retained strong test-retest reliability in both groups (ICC 0.87 and 0.82, respectively). DCS and TCD-derived phase (latency of regulation) did not significantly correlate in healthy volunteers (r = 0.12, p = 0.50) but moderately correlated in stroke patients (r = 0.65, p = 0.006). DCS-derived phase was reproducible in both groups (ICC 0.88 and 0.90, respectively). High-frequency DCS is a promising non-invasive bedside technique that can be leveraged to quantify dCA from resting-state data, but the discrepancy between TCD and DCS-derived phase requires further investigation.

Association of Chronic Kidney Disease With Risk of Intracerebral Hemorrhage.

Importance: The evidence linking chronic kidney disease (CKD) to spontaneous intracerebral hemorrhage (ICH) is inconclusive owing to possible confounding by comorbidities that frequently coexist in patients with these 2 diseases. Objective: To determine whether there is an association between CKD and ICH risk. Design, Setting, and Participants: A 3-stage study that combined observational and genetic analyses was conducted. First, the association between CKD and ICH risk was tested in the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study, a multicenter case-control study in the US. All participants with available data on CKD from ERICH were included. Second, this analysis was replicated in the UK Biobank (UKB), an ongoing population study in the UK. All participants in the UKB were included in this study. Third, mendelian randomization analyses were implemented in the UKB using 27 CKD-related genetic variants to test for genetic associations. ERICH was conducted from August 1, 2010, to August 1, 2017, and observed participants for 1 year. The UKB enrolled participants between 2006 and 2010 and will continue to observe them for 30 years. Data analysis was performed from November 11, 2019, to May 10, 2022. Exposures: CKD stages 1 to 5. Main Outcomes and Measures: The outcome of interest was ICH, ascertained in ERICH via expert review of neuroimages and in the UKB via a combination of self-reported data and International Statistical Classification of Diseases, Tenth Revision, codes. Results: In the ERICH study, a total of 2914 participants with ICH and 2954 controls who had available data on CKD were evaluated (mean [SD] age, 61.6 [14.0] years; 2433 female participants [41.5%]; 3435 male participants [58.5%]); CKD was found to be independently associated with higher risk of ICH (odds ratio [OR], 1.95; 95% CI, 1.35-2.89; P < .001). This association was not modified by race and ethnicity. Replication in the UKB with 1341 participants with ICH and 501 195 controls (mean [SD] age, 56.5 [8.1] years; 273 402 female participants [54.4%]; 229 134 male participants [45.6%]) confirmed this association (OR, 1.28; 95% CI, 1.01-1.62; P = .04). Mendelian randomization analyses indicated that genetically determined CKD was associated with ICH risk (OR, 1.56; 95% CI, 1.13-2.16; P = .007). Conclusions and Relevance: In this 3-stage study that combined observational and genetic analyses among study participants enrolled in 2 large observational studies with different characteristics and study designs, CKD was consistently associated with higher risk of ICH. Mendelian randomization analyses suggest that this association was causal. Further studies are needed to identify the specific biological pathways that mediate this association.

Review of Long-Term Blood Pressure Control After Intracerebral Hemorrhage: Challenges and Opportunities.

Blood pressure (BP) is the most important modifiable risk factor for intracerebral hemorrhage (ICH). Elevated BP is associated with an increased risk of ICH, worse outcome after ICH, and in survivors, higher risks of recurrent ICH, ischemic stroke, myocardial infarction, and cognitive impairment/dementia. As intensive BP control probably improves the chances of recovery from acute ICH, the early use of intravenous or oral medications to achieve a systolic BP goal of <140 mm Hg within the first few hours of presentation is reasonable for being applied in most patients. In the long-term, oral antihypertensive drugs should be titrated as soon as possible to achieve a goal BP <130/80 mm Hg and again in all ICH patients regardless of age, location, or presumed mechanism of ICH. The degree of sustained BP reduction, rather than the choice of BP-lowering agent(s), is the most important factor for optimizing risk reduction, with varying combinations of thiazide-type diuretics, long-acting calcium channel blockers, ACE (angiotensin-converting enzyme) inhibitors or angiotensin receptor blockers, being the mainstay of therapy. As most patients will require multiple BP-lowering agents, and physician inertia and poor adherence are major barriers to effective BP control, single-pill combination therapy should be considered as the choice of management where available. Increased population and clinician awareness, and innovations to solving patient, provider, and social factors, have much to offer for improving BP control after ICH and more broadly across high-risk groups. It is critical that all physicians, especially those managing ICH patients, emphasize the importance of BP control in their practice.

Cerebral Infarction due to Severe ADAMTS-13 Deficiency with Normal Hematological Parameters: A Cause of Cryptogenic Stroke.

OBJECTIVES: Thrombotic thrombocytopenic purpura (TTP) is a microangiopathy resulting from an inherited or acquired severe deficiency in a disintegrin and metalloproteinase called ADAMTS-13. Acquired or immune TTP is classically described as a pentad of microangiopathic hemolytic anemia (MAHA), thrombocytopenia, fever, renal insufficiency and neurological symptoms. Thrombotic thrombocytopenic purpura has been linked to stroke with the presence of hematologic abnormalities but whether or not severe ADAMTS-13 deficiency can cause stroke without hematological abnormalities is unknown. MATERIALS AND METHODS: As part of routine clinical care, we identified four cases of recurrent stroke attributed to severe deficiency of ADAMTS-13. We also conducted a search of a centralized electronic health record database including all inpatients and outpatient charts at a single academic medical center over the last ten years in an attempt to identify additional cases. RESULTS: Here we present four cases of stroke and severe ADAMTS-13 deficiency where stroke episodes occurred without microangiopathic hemolytic anemia or severe thrombocytopenia. These cases show the need to consider severe ADAMTS-13 deficiency in the setting of recurrent cryptogenic stroke in young patients. CONCLUSIONS AND RELEVANCE: TTP directed therapies may be considered for patients with recurrent stroke who have extremely low ADAMTS-13 levels, even when platelet and hemoglobin values are normal.

Differences in Inpatient Insertable Cardiac Monitor Placement after Ischemic Stroke.

BACKGROUND AND PURPOSE: Cryptogenic stroke accounts for 30% of ischemic stroke and in such patients, cardiac monitoring leads to increased detection of AF, increased utilization of anticoagulation, and decreased risk of recurrent stroke. We aim to identify differences in inpatient utilization of implantable cardiac monitors (ICMs) in patients with ischemic stroke. METHODS: This is an analysis of the National Inpatient Sample. We included all ischemic stroke hospitalizations nation-wide between Jan 1st 2016 and Dec 31st 2018. We excluded patients with history of atrial fibrillation or atrial flutter. We compared survey weighted baseline demographics and characteristics between patients who received an inpatient ICM versus those who didn't using logistic regression models. RESULTS: We identified a weighted total 1,069,395 patients who met the inclusion criteria; 2.2% received an inpatient ICM. In multivariable analyses, factors associated with decreased odds of inpatient ICM placement including Black race (OR 0.76 95% CI 0.68 - 0.84, p < 0.001), residence in a micropolitan area (OR 0.79 95% CI 0.67 - 0.94, p = 0.008), hospital region [Midwest (OR 0.74 95% CI 0.61 - 0.90, p = 0.002), South (OR 0.68 95% CI 0.57 - 0.81, p < 0.001), and West (OR 0.37 95% CI 0.29 - 0.45, p < 0.001)], hospital bed size [small (OR 0.38 95% CI 0.39-0.46, p < 0.001) and medium hospital bed size (OR 0.73 95% CI 0.63 - 0.84, p < 0.001)], insurance status [Medicaid (OR 0.86 95% CI 0.76 - 0.98, p = 0.02) and self-pay (OR 0.51 95% CI 0.41 - 0.62, p < 0.001)], and non-teaching hospital (OR 0.52 95% CI 0.47 - 0.60, p < 0.001). CONCLUSIONS: There are important differences in inpatient ICM placement in patients with ischemic stroke highlighting disparities in inpatient care for patients hospitalized with ischemic stroke. More studies are needed to validate our findings.

Dual-Antiplatelet Therapy May Not Be Associated With an Increased Risk of In-hospital Bleeding in Patients With Moderate or Severe Ischemic Stroke.

Background and Purpose: Dual antiplatelet therapy (DAPT), compared to single antiplatelet therapy (SAPT), lowers the risk of stroke or death early after TIA and minor ischemic stroke. Prior trials excluded moderate to severe strokes, due to a potential increased risk of bleeding. We aimed to compare in-hospital bleeding rates in SAPT and DAPT patients with moderate or severe stroke (defined by NIHSS ≥4). Methods: We performed a retrospective cohort study of ischemic stroke over a 2-year period with admission NIHSS ≥4. The primary outcome was symptomatic intracranial hemorrhage (ICH) with any change in NIHSS. Secondary outcomes included systemic bleeding and major bleeding, a composite of serious systemic bleeding and symptomatic ICH. We performed analyses stratified by stroke severity (NIHSS 4-7 vs. 8+) and by preceding use of tPA and/or thrombectomy. Univariate followed by multivariate logistic regression evaluated whether DAPT was independently associated with bleeding. Results: Of 377 patients who met our inclusion criteria, 148 received DAPT (39%). Symptomatic ICH was less common with DAPT compared to SAPT (0.7 vs. 6.4%, p < 0.01), as was the composite of major bleeding (2.1 vs. 7.6%, p = 0.03). Symptomatic ICH was numerically less frequent in the DAPT group, but not statistically significant, when stratified by stroke severity (NIHSS 4-7: 0 vs. 5.9%, p = 0.06; NIHSS 8+: 1.5 vs. 6.6%, p = 0.18) and by treatment with tPA and/or thrombectomy (Yes: 2.6 vs. 9.1%, p = 0.30; No: 0 vs. 2.9%, p = 0.25). DAPT was not associated with major bleeding in either the univariate or the multivariate regression. Conclusions: In this single center cohort, symptomatic ICH and the composite of serious systemic bleeding and symptomatic ICH was rare in patients on DAPT. Relative to single antiplatelet therapy DAPT was not associated with an increased risk of in-hospital bleeding in patients with moderate and severe ischemic stroke.

Early Inflammatory Cytokine Expression in Cerebrospinal Fluid of Patients with Spontaneous Intraventricular Hemorrhage.

We investigated cerebrospinal fluid (CSF) expression of inflammatory cytokines and their relationship with spontaneous intracerebral and intraventricular hemorrhage (ICH, IVH) and perihematomal edema (PHE) volumes in patients with acute IVH. Twenty-eight adults with IVH requiring external ventricular drainage for obstructive hydrocephalus had cerebrospinal fluid (CSF) collected for up to 10 days and had levels of interleukin-1α (IL-1α), IL-1ß, IL-6, IL-8, IL-10, tumor necrosis factor-α (TNFα), and C-C motif chemokine ligand CCL2 measured using enzyme-linked immunosorbent assay. Median [IQR] ICH and IVH volumes at baseline (T0) were 19.8 [5.8-48.8] and 14.3 [5.3-38] mL respectively. Mean levels of IL-1ß, IL-6, IL-10, TNF-α, and CCL2 peaked early compared to day 9-10 (p < 0.05) and decreased across subsequent time periods. Levels of IL-1ß, IL-6, IL-8, IL-10, and CCL2 had positive correlations with IVH volume at days 3-8 whereas positive correlations with ICH volume occurred earlier at day 1-2. Significant correlations were found with PHE volume for IL-6, IL-10 and CCL2 at day 1-2 and with relative PHE at days 7-8 or 9-10 for IL-1ß, IL-6, IL-8, and IL-10. Time trends of CSF cytokines support experimental data suggesting association of cerebral inflammatory responses with ICH/IVH severity. Pro-inflammatory markers are potential targets for injury reduction.

Blood flow response to orthostatic challenge identifies signatures of the failure of static cerebral autoregulation in patients with cerebrovascular disease.

BACKGROUND: The cortical microvascular cerebral blood flow response (CBF) to different changes in head-of-bed (HOB) position has been shown to be altered in acute ischemic stroke (AIS) by diffuse correlation spectroscopy (DCS) technique. However, the relationship between these relative ΔCBF changes and associated systemic blood pressure changes has not been studied, even though blood pressure is a major driver of cerebral blood flow. METHODS: Transcranial DCS data from four studies measuring bilateral frontal microvascular cerebral blood flow in healthy controls (n = 15), patients with asymptomatic severe internal carotid artery stenosis (ICA, n = 27), and patients with acute ischemic stroke (AIS, n = 72) were aggregated. DCS-measured CBF was measured in response to a short head-of-bed (HOB) position manipulation protocol (supine/elevated/supine, 5 min at each position). In a sub-group (AIS, n = 26; ICA, n = 14; control, n = 15), mean arterial pressure (MAP) was measured dynamically during the protocol. RESULTS: After elevated positioning, DCS CBF returned to baseline supine values in controls (p = 0.890) but not in patients with AIS (9.6% [6.0,13.3], mean 95% CI, p < 0.001) or ICA stenosis (8.6% [3.1,14.0], p = 0.003)). MAP in AIS patients did not return to baseline values (2.6 mmHg [0.5, 4.7], p = 0.018), but in ICA stenosis patients and controls did. Instead ipsilesional but not contralesional CBF was correlated with MAP (AIS 6.0%/mmHg [- 2.4,14.3], p = 0.038; ICA stenosis 11.0%/mmHg [2.4,19.5], p < 0.001). CONCLUSIONS: The observed associations between ipsilateral CBF and MAP suggest that short HOB position changes may elicit deficits in cerebral autoregulation in cerebrovascular disorders. Additional research is required to further characterize this phenomenon.