Search

Driven by autonomous molecular clocks that are synchronized by a master pacemaker in the suprachiasmatic nucleus, cardiac physiology fluctuates in diurnal rhythms that can be partly or entirely circadian. Cardiac contractility, metabolism, and electrophysiology, all have diurnal rhythms, as does the neurohumoral control of cardiac and kidney function. In this review, we discuss the evidence that circadian biology regulates cardiac function, how molecular clocks may relate to the pathogenesis of heart failure, and how chronotherapeutics might be applied in heart failure. Disrupting molecular clocks can lead to heart failure in animal models, and the myocardial response to injury seems to be conditioned by the time of day. Human studies are consistent with these findings, and they implicate the clock and circadian rhythms in the pathogenesis of heart failure. Certain circadian rhythms are maintained in patients with heart failure, a factor that can guide optimal timing of therapy. Pharmacologic and nonpharmacologic manipulation of circadian rhythms and molecular clocks show promise in the prevention and treatment of heart failure.

Introduction: Up to 25% of strokes are recognized upon awakening. Recent studies have demonstrated that a “tissue clock” rather than a time clock can be used to identify patients who may benefit from intravenous thrombolytics (IVT) beyond 4.5 hours from last known well (LKW). Consistent access to hyperacute MRI limits many centers from treating wake-up stroke patients. We created a formal protocol of clinical and imaging criteria to standardize evaluation and management of wake-up strokes. Methods: This retrospective, observational study reviewed consecutive patients admitted to our Comprehensive Stroke Center who qualified for the wake-up protocol between February 2022 and June 2022. The implemented protocol, based on clinical trials’ inclusion criteria, is comprised of the following: 1) arrival within 12 hours from LKW and within 4.5 hours from symptom discovery; 2) high suspicion for acute ischemic stroke; 3) no contraindication to MRI; 4) NIHSS of at least 4; 5) baseline mRS 0-3; 6) no absolute contraindications to IVT. For patients meeting above inclusion criteria, emergent MRI with perfusion was performed. Diffusion-FLAIR mismatch (signal intensity ratio) and diffusion-perfusion mismatch were reviewed to determine thrombolysis eligibility by a trained neuroradiologist or vascular neurologist. Results: Ten patients qualified for the wake-up protocol in the first five months of protocol implementation. Median NIHSS was 7, median LKW to arrival time was 8 hours, and median door to MRI time was 72.5 minutes. A final diagnosis of ischemic stroke was made in 80% of these cases. Overall, 50% were eligible for IVT based on our criteria, and 30% received thrombolysis. Median door to needle time was 92 minutes (range 75-117). There were no symptomatic intracranial hemorrhages. All patients treated with IVT were discharged home with no to minimal residual deficits with mRS 0-1 and median NIHSS at discharge of 2 (range 0-4). Conclusion: A formal protocol for wake-up stroke management allowed a streamlined approach to expand the number of IVT-eligible cases. Continued efforts are needed to improve door to needle times in such cases and to follow clinical courses of treated patients.

Background Carotid webs (CaWs) may explain embolic strokes particularly in young patients with cerebral embolism of otherwise undetermined cause. We aim to describe the radiological patterns of infarction in patients with symptomatic CaWs. Methods Retrospective analysis of a symptomatic CaW database (September 2014–July 2019) from 2 comprehensive stroke centers. Magnetic resonance imaging scans were reviewed independently by 2 blinded raters. Patterns of acute infarction included territorial (involving ≥2 arterial subdivisions), cortical (affecting 1 arterial subdivision), 1or multiple small cortical infarcts, borderzone infarcts (cortical or internal), striatocapsular lacunes ( Results Forty symptomatic patients with CaW who had infarction were identified. The median age of patients was 49 years (interquartile range, 41–57 years), 22% were women, and 78% were of Black race. The median National Institute of Health Stroke Scale was 13 (interquartile range, 4–17), noncontrast Alberta Stroke Program Early CT Score was 8 (interquartile range, 7–8), and 13 (33%) patients received intravenous alteplase. Thirty‐four (85%) individuals presented with large vessel occlusion strokes (9% intracranial internal carotid artery, 62% middle cerebral artery M1 segment, 29% M2 segment). Sixty‐three percent of patients had right hemispheric strokes and 85% large vessel occlusion. Most patients (98%) had cortical infarcts: 30% were territorial, 38% affected 1 subdivision, and 63% had ≥1 small cortical infarct. Ten percent of the patients had infarcts involving borderzone areas. Fifteen percent of patients had striatocapsular lacunes, all of which had a concomitant cortical infarction. Five percent of patients had imaging evidence of previous strokes (all cortical and within the CaW vascular territory) and 20% had leukoaraiosis (18% grade 1 and 2% grade 2). Conclusion Acute cerebral infarction attributed to CaW were all compatible with an embolic mechanism. CaW should be considered in the workup of patients with cryptogenic strokes as a potential source of embolism.

Coronavirus Disease 2019 (COVID-19), caused by the novel Severe Acute Respiratory Syndrome-associated Coronavirus 2 (SARS-CoV-2), has become a global threat to public health. COVID-19 is more pathogenic and infectious than the prior 2002 pandemic caused by SARS-CoV-1. The pathogenesis of certain disease manifestations in COVID-19 such as diffuse alveolar damage (DAD) are thought to be similar to SARS-CoV-1. However, the exact pathogenesis of COVID-19 related deaths remains poorly understood. The aim of this article was to systematically summarize the rapidly emerging literature regarding COVID-19 autopsies. A meta-analysis was also conducted based on data accrued from preprint and published articles on COVID-19 (n=241 patients) and the results compared with postmortem findings associated with SARS-CoV-1 deaths (n=91 patients). Both autopsy groups included mostly adults of median age 70 years with COVID-19 and 50 years with SARS-CoV-1. Overall, prevalence of DAD was more common in SARS-CoV-1 (100.0%) than COVID-19 (80.9%) autopsies (P=0.001). Extrapulmonary findings among both groups were not statistically significant except for hepatic necrosis (P

Objective:The International Patterns of Opioid Prescribing study compares postoperative opioid prescribing patterns in the United States (US) versus the rest of the world.Summary of Background Data:The US is in the middle of an unprecedented opioid epidemic. Diversion of unused opioids contributes t

Introduction: Direct oral anticoagulants (DOACs) have emerged as a potential anticoagulant therapy for patients with cerebral venous thrombosis (CVT). We conducted a systematic review and meta-analysis comparing DOACs versus vitamin K antagonists (VKAs) for treatment of CVT. Methods: We registered the review in PROSPERO (registration number CRD42021228800). We searched Medline, Embase, CINAHL, and the Web of Science Core Collection from January 1, 2007, to May 26, 2021. We included randomized controlled trials (RCTs) and non-randomized comparative studies (NRCSs) evaluating key outcomes for efficacy (recurrent venous thromboembolism [VTE] and complete recanalization) and safety (major hemorrhage). We assessed risk of bias using the Cochrane Risk of Bias Tool 2.0 (for RCTs) and the ROBINS-I tool (for NRCSs). Where studies were sufficiently similar, we performed meta-analyses using random-effects models. This review was funded by Brown Neurology. Results: Of 8213 identified records,10 studies (1 RCT and 9 NRCSs) with a total of 662 patients (33% DOAC and 67% VKAs) met the inclusion criteria. We will present our risk of bias assessment at the conference. DOACs and VKAs had comparable efficacy: recurrent VTE (risk ratio [RR] 1.00, 95% confidence interval [CI] 0.44-2.23; I 2 =0%; 10 studies) and complete recanalization (RR 1.00, 95% CI 0.77-1.28; I 2 =0%; 6 studies). DOAC and VKA also had comparable safety: major hemorrhage (RR 0.89, 95% CI 0.37-2.14; I 2 =0%; 9 studies). Conclusions: Studies comparing DOACs with VKAs in patients with CVT consist mostly of small, non-randomized, poorly controlled studies. While the two treatments appear comparable for major efficacy and safety outcomes, large, rigorously conducted studies, preferably randomized, are needed to overcome these limitations and permit development of clinical practice guidelines for the use of DOACs in patients with CVT.

Introduction: Approximately 30% of ischemic strokes are cryptogenic and 40-50% of these patients have a patent foramen ovale (PFO) detected during work up. While the risk of ischemic stroke attributed to PFO is 0.5-1% per year, the proportion of disabling ischemic strokes in the setting of PFO is unknown. In this study, we aim to determine differences in rates and predictors of poor outcome in patients with stroke and PFO compared to those without PFO. Methods: This retrospective, observational cohort study included consecutive patients aged 18-60 admitted to our comprehensive stroke center with a diagnosis of ischemic stroke over a two-year period. modified Rankin Score (mRS) was collected at 90-days according to institutional protocol. Poor functional outcome was defined as mRS of 2-6. We compared baseline characteristics of ischemic stroke patients with PFO to those without PFO, and then determined associations with poor outcome using multivariable logistic regression that adjusted for age and stroke severity. We performed similar analyses in the subgroup of patients with cryptogenic stroke. Results: Out of 321 patients with ischemic stroke (mean age 49; 42% women), 146 had cryptogenic stroke - embolic stroke of undetermined source subtype (CS-ESUS). Baseline characteristics, demographics, and stroke severity did not differ between those with PFO when compared to those without PFO both across the entire cohort and in the subgroup of CS-ESUS. Among patients with cs-ESUS with PFO, 48% (10/21) had poor functional outcome, and the rates did not significantly differ based on ROPE score (p = 0.362). In our binary logistic regression model adjusting for age and NIHSS score, the rate of poor functional outcome in patients with CS-ESUS did not significantly differ based on presence vs. absence of PFO (OR 1.10 95% CI 0.39-3.09, p = 0.859). Conclusions: Our study suggests that a significant portion (almost 1 in 2) of cryptogenic strokes in patients with a PFO were disabling at 90 days and disability rates did not significantly differ as a function of PFO attributability of their ischemic stroke. Further studies are needed to identify patients with high-risk PFOs that may especially predispose to disabling strokes and to determine optimal primary stroke prevention strategies.

Background: Cannabinoids are hypothesized to cause cardiovascular disease including stroke; this is potentially due to dysregulation of endogenous lipid mediator endocannabinoids and their G-protein coupled receptors. Our aim is to investigate cannabinoid use in patients with acute ischemic stroke and determine associations between stroke subtype and functional outcome at 90-days. Methods: This is a retrospective, observational, cohort study of consecutive patients admitted with acute ischemic stroke to our Comprehensive Stroke Center. We included patients 60 years or younger who had a drug screen performed during their acute stroke hospitalization. We compared demographic factors, stroke subtype, and 90-day functional outcomes between the two groups (Cannabinoid positive vs. Cannabinoid negative). Stroke subtype was determined based on TOAST criteria, ESUS criteria and good outcome was defined as mRS 0-1 at 90-days. Results: We identified 256 patients who met inclusion criteria. Mean age was 50 years, 61% were men and 20% were cannabinoid positive. Cannabinoid positive patients were younger (47.0 ± 10.7 vs. 50.5 ± 8.5, p = 0.032) and more likely to test positive for cocaine (17.3% vs. 3.9%, p = 0.002). Gender and vascular risk factors including smoking were similar between cannabinoid positive and negative patients. Cannabinoid positive patients were more likely to have a stroke related to large artery atherosclerosis (23.0% vs. 10.3%, p = 0.020). In an adjusted binary regression analysis, cannabinoid use was associated with non-significantly lower odds of good outcome (OR 0.61 95% CI 0.31 -1.23, p = 0.1). Conclusions: Cannabinoid use is associated with atherosclerotic stroke subtypes and a non-significantly reduced likelihood of good functional recovery. Larger studies are needed to further test these associations.

Introduction: Venous thromboembolism (VTE) is a frequent and potentially life-threatening complication of acute ischemic stroke (AIS). We performed a nationwide analysis to evaluate rate and risk factors for VTE readmission in patients with AIS. Methods: Using the Healthcare Cost and Utilization Project (HCUP) Nationwide Readmission Database, we included adult patients with a principal discharge diagnosis of AIS from 2016 to 2018. AIS, pulmonary embolism, deep vein thrombosis and other diagnosis were identified based on standard ICD-10 CM codes. Patients who had VTE diagnosis during the index admission were excluded. We determined 90-day VTE readmission rates and trends in patients with a principal diagnosis of AIS stratified by 30-day epochs. We then constructed a stepwise binary logistic regression model to determine odds ratios (OR) of demographic and clinical factors associated with VTE readmission rates. Results: Of the 1,023,478 patients with AIS, 8378 (0.82%) had VTE during readmission and 2906 (0.28%) had VTE as principal diagnosis for readmission within 90 days of discharge. Among them, more than half (4557, 54.39% and 1581, 54.40%, respectively) of patients were readmitted within 30 days of discharge. The rate of VTE readmission decreased further away from index event (P < 0.001). In the Cox regression model, obesity (OR 1.48, 95% CI 1.24-1.76, P < 0.001), plegia of at least one limb (OR 1.24, 95% CI 1.08-1.43, P = 0.003), longer hospital length of stay (OR 1.02, 95% CI 1.01-1.02, P < 0.001), higher NIHSS (OR 1.04, 95% CI 1.03-1.05, P < 0.001) were associated with VTE readmission. Conversely, VTE readmission rates were lower in patients with a history of atrial fibrillation/flutter (OR 0.72, 95% CI 0.62-0.84, P < 0.001). Conclusion: Patients with obesity, paralysis, higher NIHSS score, or prolonged hospital length of stay are at higher risk for VTE readmission. AF strokes are less likely to have DVT/PE, perhaps due to anticoagulant use in such patients. Studies are needed to determine whether early mobilization and mechanical and/or chemical prophylaxis reduces VTE risk in high-risk patients.

Introduction : Mechanical thrombectomy (MT) has become the standard of care in patients with large vessel occlusion after trials have demonstrated (MT) improved outcomes in acute ischemic stroke (AIS) as compared to medical therapy. Despite leading to high reperfusion rates, MT patients are at high risk for recurrent ischemic events and complications of stroke. We performed an analysis to evaluate temporal trends in readmission of post‐MT among stroke patients over a three‐year period. Methods : From the Healthcare Cost and Utilization Project Nationwide Readmission Database, we obtained in‐hospital adult patient data with a principal diagnosis of AIS in the US from 2016 to 2018. AIS, MT, thrombolysis treatment and other diagnosis were identified based on International Classification of Diseases, 10th Revision, Clinical Modification codes. We compared the trend of 30‐day readmission in AIS patients who received MT, thrombolysis only and neither treatment with linear regression. Using Clinical Classifications Software Refined tool, we categorized the readmission principal diagnoses of patients underwent MT into groups. All analyses were performed in Stata/SE 15.1 software. Results : Of the 1,271,958 patients admitted from throughout the US with AIS within the study period, 1,130,737 (88.90%) did not receive thrombolysis nor MT, 100,737 (7.92%) received thrombolysis only, and 40,849 (3.21%) underwent MT with or without thrombolysis. The endovascular treatment rate doubled from 2016 (2.40%) to 2018 (4.11%, p < 0.0001). From 2016 to 2018, the readmission rate has significantly decreased from 15.00% to 12.04% (absolute risk reduction (ARR) 2.96%, p = 0.0001) in patients who underwent MT, decreased from 10.46% to 9.51% (ARR 0.95%, p = 0.0097) in patients who received thrombolysis only, and decreased from 11.96% to 11.56% (ARR 0.40%, p = 0.0130) in patients received neither therapy. Among all the patients who underwent MT during the three‐year period, sepsis (1.88%), cerebral infarction (1.59%), sequelae of cerebral infarction (0.82%), cardiac dysrhythmias (0.67%) and heart failure (0.49%) were the most common principal readmission diagnoses. From 2016 to 2018, there were significant decreases in rate of readmissions with septic infection (p = 0.0001), sequelae of cerebral infarction (p < 0.0001), and heart failure (p = 0.0123), but no significant change in cerebral infarction (p = 0.4853) and cardiac dysrhythmias (p = 0.1834). Conclusions : Over three years, the rate of readmissions in AIS patients receiving MT significantly declined, particularly in rate of readmissions in sepsis, sequelae of cerebral infarction, and heart failure. Improved reperfusion rate and better outcomes may explain the reduction in post‐MT complication rate, which needs further studies.

Classifying diffuse large B-cell lymphoma (DLBCL) according to the cell-of-origin (COO) was first proposed using gene expression profiling; accordingly, DLBCL is classified into germinal-center B-cell type and activated B-cell type. Immunohistochemistry (IHC)-based classification using different algorithms is used widely due to the ability to use formalin-fixed paraffin-embedded tissue. Recently, newer techniques using RNA expression from formalin-fixed paraffin-embedded were introduced including the nCounter NanoString platform assay. In this brief report, we study the degree of concordance between the NanoString assay and 6 commonly utilized IHC-based algorithms to classify DLBCL cases by COO. Stains for CD10, BCL2, BCL6, FOXP-1, MUM-1, and LOM2 were used to classify a cohort of DLBCL by COO according to the respective IHC-algorithms. Then, RNA was extracted from the same cases for NanoString assay classification. The degree of concordance was calculated between the NanoString classification and each IHC-algorithm as well as among the different IHC-algorithm themselves. The concordance in COO classification of DLBCL between NanonoString assay and IHC-based algorithms is variable depending on the used IHC-algorithm; the highest concordance is seen with the Visco algorithm (κ=0.69; P=0.001). Therefore, discrepancies between the recently introduced NanoString assay and the commonly utilized IHC-algorithms are expected to some extent and should be taken into consideration when interpreting conflicting results.

Myeloid sarcoma (MS) is defined as an extramedullary mass-forming lesion composed of immature myeloid cells. It is a rare but well-known manifestation of acute myeloid leukemia. Pediatrics testicular MS may pose a possible diagnostic challenge, an issue that is underscored in the few testicular pediatric MS cases reported in the literature. Herein, we report a series of 5 cases of pediatric testicular MS that are evaluated at the morphologic and immunohistochemical levels with correlation with the KMT2A (MLL) rearrangement status. Three patients presented with no prior history of acute myeloid leukemia. All 5 cases showed monoblastic morphology; positive for CD33, CD43, CD68, CD163, CD4 (dim), and lysozyme; and negative for CD10, CD34, CD117, and myeloperoxidase. KMT2A (MLL) rearrangement was detected in 4 of the 5 cases. In the literature, 8 more cases of pediatric testicular lymphoma were reported. Most of them showed monocytic differentiation and KMT2A (MLL) rearrangement was reported in 3 of the cases. In conclusions, testicular MS in pediatric patients shows monoblastic differentiation which may be attributed to the KMT2A (MLL) rearrangement. We also highlight the importance of using an extended immunohistochemistry panel in the diagnosis of MS.

Background: Prior studies identified an increased risk of hematoma expansion (HE) in patients with spontaneous intracerebral hemorrhage (ICH) and lower admission hemoglobin (Hgb) levels. We aimed to externally validate these findings in a separate cohort of ICH patients. Methods: We performed an observational cohort study on consecutive patients with ICH admitted to a Comprehensive Stroke Center over 2 years, using data from an institutional ICH registry. We excluded patients with secondary, non-spontaneous ICH etiologies, as well as patients who arrived >24 hours from symptom onset. Data on HE (defined as an increase of >33% or >6 mL) and 3-month outcomes were prospectively collected, while admission laboratory values were retrospectively abstracted. We compared admission Hgb, INR, and platelet count (Plt) between patients with and without HE, then determined associations between Hgb, HE, and unfavorable 3-month outcomes (modified Rankin Scale 4-6) after adjusting for established ICH predictors, any anticoagulant use, and laboratory markers of coagulopathy with multivariable logistic regression analysis. Results: Of 375 patients, mean age was 73.6 [SD 13.5], 50% (n=187) were male, 85% (n=317) were white, and 19% (n=71) had HE. Admission Hgb values were similar in patients with and without HE (mean [SD] 13.1 [1.8] g/dl vs. 13.1 [1.9] g/dl, p=0.98), as were INR values (median [IQR] 1.1 [1-1.3] vs. 1.1 [1.0-1.2], p=0.15), although patients with HE had modestly lower Plt (median [IQR] 181 [155-230] x 10 9 /l vs. 207 [170-253] x 10 9 /l, p=0.02). In our multivariable models, Hgb was not associated with HE (OR 0.97, 95% CI 0.83-1.12), but odds of unfavorable 3-month outcome increased with lower Hgb levels (OR 0.81 per 1 g/dL Hgb, 95% CI 0.68-0.96). Conclusion: Our study did not confirm prior associations between Hgb and HE, suggesting that if Hgb is implicated in HE, its effects are likely modest. However, Hgb may mediate outcomes in ICH patients via alternative mechanisms.

Introduction: The carotid web is a compelling potential mechanism of embolic ischemic stroke. In this study, we perform a systematic review and meta-analysis to determine the prevalence of ipsilesional carotid webs in patients with acute ischemic stroke. Methods: We performed a systematic review of prospective and retrospective observational studies enrolling consecutive patients with acute ischemic stroke. We included only studies in which high quality imaging of the cervical vessels was performed and in which the presence or absence of carotid web was adjudicated based on established criteria. The prevalence of carotid web was calculated in each study and pooled prevalence calculated via a random effects model. We also calculated relative risks of carotid web ipsilateral versus contralateral to stroke in the same pool of patients and performed sensitivity analyses including patients with cryptogenic stroke, patients less than 60 and patients with cryptogenic stroke Results: A systematic review yielded 3,814 patients from 11 studies of whom 1,127 had cryptogenic stroke. We identified 4 studies in which we could derive data on patients Figure A-C ). The pooled prevalence of ipsilateral carotid web in patients 2 = 66.1%) ( Figure D ). Discussion: Carotid webs are more common in young patients with ESUS than in other stroke subtypes. Future studies concerning the diagnosis and secondary prevention of stroke associated with carotid web should focus on this population.

Supplemental Digital Content is available in the text., Coronavirus Disease 2019 (COVID-19), caused by the novel Severe Acute Respiratory Syndrome–associated Coronavirus 2 (SARS-CoV-2), has become a global threat to public health. COVID-19 is more pathogenic and infectious than the prior 2002 pandemic caused by SARS-CoV-1. The pathogenesis of certain disease manifestations in COVID-19 such as diffuse alveolar damage (DAD) are thought to be similar to SARS-CoV-1. However, the exact pathogenesis of COVID-19 related deaths remains poorly understood. The aim of this article was to systematically summarize the rapidly emerging literature regarding COVID-19 autopsies. A meta-analysis was also conducted based on data accrued from preprint and published articles on COVID-19 (n=241 patients) and the results compared with postmortem findings associated with SARS-CoV-1 deaths (n=91 patients). Both autopsy groups included mostly adults of median age 70 years with COVID-19 and 50 years with SARS-CoV-1. Overall, prevalence of DAD was more common in SARS-CoV-1 (100.0%) than COVID-19 (80.9%) autopsies (P=0.001). Extrapulmonary findings among both groups were not statistically significant except for hepatic necrosis (P

Introduction: Carotid web is a putative mechanism of cryptogenic ischemic stroke. We aimed to determine the prevalence of carotid web based on assigned stroke mechanism, and hypothesized that carotid webs would be found more frequently in younger cryptogenic stroke patients. Methods: We performed a single-center retrospective cohort study using institutional registry data from consecutive patients with confirmed anterior circulation ischemic stroke between July 2015-September 2017. We reviewed all available computed tomography angiogram (CTA) studies of the neck, and excluded patients who did not have a high-quality CTA of the neck performed. Carotid web was defined as a thin shelf of non-calcified tissue protruding into the lumen of the internal carotid artery immediately distal to the bifurcation, best visualized on sagittal oblique imaging and evident as a small septum on axial imaging. Stroke subtype was adjudicated a priori using validated methods, and we compared relevant risk factors in patients with cryptogenic stroke with and without carotid web. Results: We identified 882 patients with anterior circulation stroke who had a CTA neck available for review (49.3% male, 30% cryptogenic). A total of 7 patients (0.8%) were found to have carotid webs, of which 4 were ipsilateral to a patient’s stroke; all patients with ipsilateral carotid webs were adjudicated to have cryptogenic stroke. Patients with carotid web were younger than other patients in our cohort (age 49.0±14.6 vs. 72.2±14.9 years, p=0.003), and none of them had a history of hypertension (0% vs. 72%, p=0.04). In patients with cryptogenic stroke, overall prevalence of carotid webs was 1.5%, but the prevalence was significantly higher in younger cryptogenic stroke patients (age Discussion: Carotid web may represent an under-recognized occult mechanism of cryptogenic stroke, particularly amongst younger patients.

Introduction: Central retinal artery occlusion (CRAO) is a form of ischemic stroke and necessitates a comprehensive workup, including for cardioembolic sources such as atrial fibrillation (AF). However, the incidence of new AF diagnosed after CRAO is unknown. We aimed to examine the incidence of new, cardiac device-detected AF after CRAO in a large population-based cohort. Methods: Using patient-level data from the Optum® de-identified EHR dataset (2007-2017) linked with Medtronic implantable cardiac device data, we identified patients that had a diagnosis-code corresponding to CRAO and no known history of AF, and who also had either a device in-situ at the time of CRAO or implanted ≤1 year post-CRAO with continuous AF monitoring data available. AF incidence was defined as ≥2 minutes of device-detected AF in a day. Results: Of 467,167 patients screened, 246/433 (56.8%) with CRAO had no history of AF, of whom 39 had an eligible implantable cardiac device (mean age 66.7±14.8, 41.0% female). Prevalence of vascular risk factors was high (hypertension, 71.8%; hyperlipidemia, 61.5%; coronary artery disease, 46.2%). Within 3 months, 7.7% of these patients (n=3) had device-detected AF. At 36 months, 33.3% of patients (n=13). The maximum daily AF burden post CRAO ranged from 2 minutes to 24 hours with a mean of 390±530 minutes. Of the patients with device-detected AF, 9 were found by an implantable cardiac monitor and 4 by pacemaker or defibrillator. Discussion: The rate of long-term AF detection after CRAO was high in patients with implanted cardiac devices, and appears comparable with rates seen after cryptogenic ischemic stroke and in other high-risk populations. Our findings warrant future prospective studies not limited by selection bias.

Introduction: Spontaneous intracerebral hemorrhage (ICH) most commonly arises due to primary etiologies such as hypertensive or cerebral amyloid angiopathy (CAA), but may also occur due to underlying secondary causes such as vascular malformations or intracranial neoplasms. However, focal mass effect may potentially obscure underlying lesions on neuroimaging performed during the acute phase of ICH, and follow-up imaging is often recommended. We sought to determine the yield of interval magnetic resonance imaging (MRI) in identifying cryptogenic ICH etiologies. Methods: We performed a single-center descriptive cohort study of consecutive patients enrolled in an institutional ICH registry over 12 months. ICH features including etiology and acute neuroimaging were prospectively adjudicated, while planned interval follow-up imaging was retrospectively reviewed. We determined the frequency of newly-discovered findings on interval MRI, and classified new findings according to whether or not they contributed meaningfully to patient management. Results: There were 241 ICH patients in our cohort who survived to discharge and did not have MRI-incompatible devices; 44 had planned follow-up imaging and 33 ultimately completed a follow-up MRI. Mean interval between initial and follow-up MRI was 61 (±34) days. New findings were identified in 33% of follow-up cases (11/33), with changes in patient management occurring in 12% (4/33). Age (59.4 vs. 61.5, p=0.74), sex (45% vs. 45% male, p>0.99), and secondary ICH score (median 3 [IQR 2-3] vs. 3 [1-4], p=0.87) were not significantly different between patients who had new findings and those who did not. New findings included cavernoma (n=4; 1 underwent resection), CAA-related changes (n=3), intracranial malignancy (n=2; 1 transitioned to hospice care, 1 led to cancer workup), new embolic stroke (n=1, underwent extended cardiac monitoring), and demyelination (n=1). Conclusions: Interval MRI aided in diagnosing ICH etiology in one-third of patients who received one, though few cases led to direct actionable changes in patient management.

Background: White matter hyperintensity (WMH), also known as leukoaraiosis, is commonly visualized as abnormal T2 signal in the deep and subcortical white matter on Magnetic Resonance Imaging (MRI). It is also commonly associated with aging, diabetes, hypertension and cerebrovascular disease. The Fazekas (F) scoring system is a subjective tool commonly used to assess WMH, but no volumetric analysis has been published showing how the scores correspond to true quantities of white matter disease. Methods: MRIs performed on inpatients and outpatients at our tertiary care institution between 2015 and 2017 were reviewed and their relative WMH was scored by one author trained in using the Fazekas scale. Using 3D Slicer 4.9, manual segmentations of WMH were completed and a 3D model was created to quantify the amount of WMH. Univariate analysis and ANOVA tests were run to determine the association of each Fazekas score with volume of WMH. Results: Among the 198 patients in our study (53% female), 163 had WMH (F1 n=66, F2 n=49, F3 n=48). Ranges of WMH in each group were 0.1-8.3 mL in Fazekas 1 (mean = 3.7, SD = 2.3), 6.0-17.7 mL in Fazekas 2 (mean = 10.8, SD = 3.1), and 14.2-77.2 mL in Fazekas 3 (mean = 35.2, SD = 17.9); if 11 outliers above 50 mL were excluded, the range for Fazekas 3 was 14.2-47.0 mL (mean = 27.1, SD = 8.9). When comparing data between groups, both the comparison between F1+2 (t-value = 14.1, p Conclusion: When accurately trained in assigning Fazekas scores to patient’s WMH, each of the scores appears to represent an approximate range of distinct volumes for WMH. Studies have shown that the presence and extent of WMH is a predictor for future development of stroke. These results should be validated in subsequent studies.

Clinical care of acute stroke patients can be handled by multiple specialties yet the concept of “strokophobia”, or the fear of dealing with stroke patients has not been explored in the literature. We explore some of the roots of that fear in residents of the neurology, emergency medicine (EM) and internal medicine (IM) specialties. An anonymous survey was sent to neurology, IM and EM residents at two different academic institutions. The survey inquired about the respondent’s demographics, training, and the first time the had a strong discomfort dealing with stroke. More detailed questions followed regarding some of the common perceived misconceptions and reasons behind the fear of caring for stroke patients. The questionnaire also inquired about some available resources to mitigate that fear. Of the 47 respondents, 47% were male. 57% were in IM, 38% were in neurology, and 4% from EM. 23% were in their PGY1 of training, 30 % were PGY2, 32% PGY3, and 15% PGY4. Most residents (83%) had an inpatient component in their neurology clerkship. 66% report having some fear in dealing with stroke patients. 28% report the fear to originally stem from the clinical years of medical school and 28% during residency. 40% of residents agreed that more neuroanatomy teaching is needed and 36% did not think enough education was given in medical school. 11% did not have a neurology clerkship in their medical school, 4% did not have an opportunity to work with a neurologist in medical school. 25% of residents report having limited exposure to stroke patients. 23% of residents consult neurology out of fear of missing significant pathology, while 23% were not comfortable with their exam skills. 38 % residents blame excessive paperwork for the lack of education while 23% think it was witnessing some attendings uncomfortable with stroke patients. The high acuity of these patients would deter 30% of the residents from caring for them. 11% of residents shy away due to having to establish adequate time windows or asking for help. 72% agree that more hands-on teaching is needed while 38% state that more tutorial videos could be helpful. In this first-ever exploratory analysis of strokophobia, the results show that the phenomenon is prevalent and more education is needed in order to mitigate it amongst residents.

Introduction: The detection of atrial fibrillation (AF) is a crucial component of ischemic stroke secondary prevention. Inpatient cardiac telemetry is part of the structured inpatient workup for ischemic stroke but the yield of telemetry is unknown when ipsilateral, hemodynamically-significant large artery atherosclerosis is identified at the time of initial presentation. Methods: We performed a single-center, retrospective, cohort study utilizing data from an institutional quality improvement database. We identified consecutive patients with acute ischemic stroke presenting between July 2015 and September 2017. We included patients with hemodynamically-significant (>50%) large artery stenosis in the arterial territory subserving the region of infarct. We excluded patients with a known history of AF. We determined the yield of an electrocardiogram, inpatient telemetry and outpatient cardiac event monitoring in detecting new AF. Groups with and without AF were compared using unpaired student’s T-test for continuous variables and Chi 2 test for categorical variables. Results: We identified 1435 patients presenting to our institution during the study period of whom 209 (14.6%) met inclusion criteria. Patients were aged 69.37±12.6 years and 33% were female. Of these patients, 19 (9.1%) were found to have new AF during their hospitalization and a further 2 (1%) were found to have AF on extended cardiac monitoring. Thirty seven patients had 30-day cardiac monitoring performed after hospitalization and the yield on this was 5.4% for the detection of AF. Patients with AF were older (76.29±11.31 years vs. 68.60±12.58 years, p=0.008) and had higher rates of hypertension (94% vs. 75%, p=0.04) and hyperlipidemia (72% vs. 52%, p=0.09). In all patients, anticoagulation was planned after the discovery of AF. Discussion: Inpatient cardiac telemetry detects new atrial fibrillation in 9.1% of patients known to have hemodynamically-significant large artery disease at the time of initial presentation. The yield of further outpatient cardiac monitoring is lower (5%). This hypothesis-generating study is limited by its retrospective nature and the potential for selection bias.

Background and Purpose— Amyloid-β (Aβ), a peptide that accumulates in the brain and circulates in the blood of patients with Alzheimer disease, alters the regulation of cerebral blood flow and may contribute to the brain dysfunction underlying the dementia. However, the contributions of brain and circulating Aβ1–40 to the vascular dysfunction have not been elucidated. Methods— We used transgenic mice overexpressing mutated forms of the amyloid precursor protein in which Aβ1–40 is elevated in blood and brain (Tg-2576) or only in brain (Tg-SwDI). Mice were equipped with a cranial window, and the increase in cerebral blood flow induced by neural activity (whisker stimulation), or by topical application of endothelium-dependent vasodilators, was assessed by laser-Doppler flowmetry. Results— The cerebrovascular dysfunction was observed also in Tg-SwDI mice, but despite ≈40% higher levels of brain Aβ1–40, the effect was less marked than in Tg-2576 mice. Intravascular administration of Aβ1–40 elevated plasma Aβ1–40 and enhanced the dysfunction in Tg-SwDI mice, but not in Tg-2576 mice. Conclusions— The results provide evidence that Aβ1–40 acts on distinct luminal and abluminal vascular targets, the deleterious cerebrovascular effects of which are additive. Furthermore, the findings highlight the importance of circulating Aβ1–40 in the cerebrovascular dysfunction and may provide insight into the cerebrovascular alterations in conditions in which elevations in plasma Aβ1–40 occur.