Cardioembolic Stroke.

Cardioembolism accounts globally for around 25% of ischemic strokes and is more often associated with higher rates of morbidity and mortality. Potential sources of cardioembolism into the intracranial circulation include paradoxic embolism, dysrhythmias, structural heart disease, and valvular heart disease. To identify the etiology of a patient's ischemic stroke, thorough investigation of the intracardiac structures, assessment of dysrhythmias, and consideration of high-risk events such as cardiac surgery are crucial. Treatment after cardioembolic stroke can be personalized based on the underlying cardioembolic source to minimize the risk of recurrent cerebral ischemic events.

Automated intracranial vessel segmentation of 4D flow MRI data in patients with atherosclerotic stenosis using a convolutional neural network.

Introduction: Intracranial 4D flow MRI enables quantitative assessment of hemodynamics in patients with intracranial atherosclerotic disease (ICAD). However, quantitative assessments are still challenging due to the time-consuming vessel segmentation, especially in the presence of stenoses, which can often result in user variability. To improve the reproducibility and robustness as well as to accelerate data analysis, we developed an accurate, fully automated segmentation for stenosed intracranial vessels using deep learning. Methods: 154 dual-VENC 4D flow MRI scans (68 ICAD patients with stenosis, 86 healthy controls) were retrospectively selected. Manual segmentations were used as ground truth for training. For automated segmentation, deep learning was performed using a 3D U-Net. 20 randomly selected cases (10 controls, 10 patients) were separated and solely used for testing. Cross-sectional areas and flow parameters were determined in the Circle of Willis (CoW) and the sinuses. Furthermore, the flow conservation error was calculated. For statistical comparisons, Dice scores (DS), Hausdorff distance (HD), average symmetrical surface distance (ASSD), Bland-Altman analyses, and interclass correlations were computed using the manual segmentations from two independent observers as reference. Finally, three stenosis cases were analyzed in more detail by comparing the 4D flow-based segmentations with segmentations from black blood vessel wall imaging (VWI). Results: Training of the network took approximately 10 h and the average automated segmentation time was 2.2 ± 1.0 s. No significant differences in segmentation performance relative to two independent observers were observed. For the controls, mean DS was 0.85 ± 0.03 for the CoW and 0.86 ± 0.06 for the sinuses. Mean HD was 7.2 ± 1.5 mm (CoW) and 6.6 ± 3.7 mm (sinuses). Mean ASSD was 0.15 ± 0.04 mm (CoW) and 0.22 ± 0.17 mm (sinuses). For the patients, the mean DS was 0.85 ± 0.04 (CoW) and 0.82 ± 0.07 (sinuses), the HD was 8.4 ± 3.1 mm (CoW) and 5.7 ± 1.9 mm (sinuses) and the mean ASSD was 0.22 ± 0.10 mm (CoW) and 0.22 ± 0.11 mm (sinuses). Small bias and limits of agreement were observed in both cohorts for the flow parameters. The assessment of the cross-sectional lumen areas in stenosed vessels revealed very good agreement (ICC: 0.93) with the VWI segmentation but a consistent overestimation (bias ± LOA: 28.1 ± 13.9%). Discussion: Deep learning was successfully applied for fully automated segmentation of stenosed intracranial vasculatures using 4D flow MRI data. The statistical analysis of segmentation and flow metrics demonstrated very good agreement between the CNN and manual segmentation and good performance in stenosed vessels. To further improve the performance and generalization, more ICAD segmentations as well as other intracranial vascular pathologies will be considered in the future.

Household income is associated with functional outcomes in a multi-institutional cohort of patients with ischemic stroke and COVID-19.

OBJECTIVES: The COVID-19 pandemic has heightened awareness of health disparities associated with socioeconomic status (SES) across the United States. We examined whether household income is associated with functional outcomes after stroke and COVID-19. MATERIALS AND METHODS: This was a multi-institutional, retrospective cohort study of consecutively hospitalized patients with SARS-CoV-2 and radiographically confirmed stroke presenting from March through November 2020 to any of five comprehensive stroke centers in metropolitan Chicago, Illinois, USA. Zip-code-derived household income was dichotomized at the Chicago median. Logistic regression was used to examine the relationship between household income and good functional outcome (modified Rankin Scale 0-3 at discharge, after ischemic stroke). RESULTS: Across five hospitals, 159 patients were included. Black patients comprised 48.1%, White patients 38.6%, and Hispanic patients 27.7%. Median household income was $46,938 [IQR: $32,460-63,219]. Ischemic stroke occurred in 115 (72.3%) patients (median NIHSS 7, IQR: 0.5-18.5) and hemorrhagic stroke in 37 (23.7%). When controlling for age, sex, severe COVID-19, and NIHSS, patients with ischemic stroke and household income above the Chicago median were more likely to have a good functional outcome at discharge (OR 7.53, 95% CI 1.61 - 45.73; P=0.016). Race/ethnicity were not included in final adjusted models given collinearity with income. CONCLUSIONS: In this multi-institutional study of hospitalized patients with stroke, those residing in higher SES zip codes were more likely to have better functional outcomes, despite controlling for stroke severity and COVID-19 severity. This suggests that area-based SES factors may play a role in outcomes from stroke and COVID-19.

Carotid disease, cognition, and aging: time to redefine asymptomatic disease?

There is an increasing appreciation of the vascular contributions in the development of age-related cognitive impairment and dementia1,2. Identifying risk and maintaining cognitive health for successful aging is ever relevant in our aging population. Carotid disease, a well-established risk factor for stroke and often a harbinger of other vascular disease states, is also emerging as another vascular risk factor for age-related cognitive decline. When combined with vascular risk factors, the incidence of age-related carotid disease can be as high as 70%3,4. Historically, carotid disease has been dichotomized into two large groups in trial design, outcome measurements, and treatment decisions: symptomatic and asymptomatic carotid artery stenosis. The dichotomous distinction between asymptomatic and symptomatic carotid stenosis based on existing definitions may be limiting the care we are able to provide for patients classified as "asymptomatic" from their carotid disease. Medically, we now know that these patients should be treated with the same intensive medical therapy as those with "symptomatic" carotid disease. Emerging data also shows that hypoperfusion from asymptomatic disease may lead to significant cognitive impairment in the aging population, and it is plausible that most "age-related" cognitive changes may be reflective of vascular impairment and neurovascular dysfunction. While over the past 30 years medical, surgical, and radiological advances have pushed the field of neurovascular disease to significantly reduce the number of ischemic strokes, we are far from any meaningful interventions to prevent vascular cognitive impairment. In addition to including cognitive outcome measures, future studies of carotid disease will also benefit from including advanced neuroimaging modalities not currently utilized in standard clinical imaging protocols, such as perfusion imaging and/or functional connectivity mapping, which may provide novel data to better assess for hypoxic-ischemic changes and neurovascular dysfunction across diffuse cognitive networks. While current recommendations advise against widespread population screening for asymptomatic carotid stenosis, emerging evidence linking carotid stenosis to cognitive impairment prompts us to re-consider our approach for older patients with vascular risk factors who are at risk for cognitive decline.

Goal-Concordant Care in the Era of Advanced Stroke Therapies.

Stroke is a leading cause of disability and mortality worldwide. Recent advances in stroke care now enable patients with severe ischemic stroke owing to large vessel occlusion to safely undergo endovascular thrombectomy (EVT) up to 24 hours since their time of last known well, with the goal of improving functional outcomes by recanalization of the occluded vessel and reperfusion of downstream ischemic brain tissue. The objective of this analysis is to highlight clinical and ethical challenges related to ensuring goal-concordant care in this era of unprecedented advances in acute stroke care. Specifically, there is a salient challenge of whether advanced therapies such as EVT may be justifiably considered comfort focused, given their potential to preempt accumulated neurologic disability and suffering at the end of life. Through the lens of a patient case, we discuss key challenges, lessons learned, and suggestions for future care and research endeavors at the intersection of acute stroke care and palliative care principles. Although therapies such as thrombolysis and EVT may be considered aggressive prima facie, their potential to ameliorate additional disability and potential suffering at the end of life prompt close consideration of the proper role of these therapies on a case-by-case basis in the context of comfort-focused care. Modification to the workflow for EVT evaluations may facilitate goal-concordant care and timely resource allocation, especially for cases that involve hospital-to-hospital transfers for advanced stroke care.

Cerebrovascular Disease: Primary and Secondary Stroke Prevention.

Despite advances in earlier diagnosis and available aggressive treatments for vascular risk factors, stroke remains a leading cause of death and long-term disability worldwide. Disparities exist in stroke risk, rates of stroke, and treatment. Stroke is a heterogeneous disease with multiple additive risk factors and causes. Primary prevention of stroke focusing on risk factor modification plays an important role in reducing the burden of stroke in an aging population. Secondary prevention of recurrent strokes relies on the workup and a tailored treatment targeted at the mechanisms responsible for the incident stroke or transient ischemic attack.

A resident boot camp for reducing door-to-needle times at academic medical centers.

BACKGROUND: We sought to determine if a structured educational program for neurology residents can lower door-to-needle (DTN) times at an academic institution. METHODS: A neurology resident educational stroke boot camp was developed and implemented in April 2013. Using a prospective database of 170 consecutive acute ischemic stroke (AIS) patients treated with IV tissue plasminogen activator (tPA) in our emergency department (ED), we evaluated the effect of the intervention on DTN times. We compared DTN times and other process measures preintervention and postintervention. p Values < 0.05 were considered significant. RESULTS: The proportion of AIS patients treated with tPA within 60 minutes of arrival to our ED tripled from 18.1% preintervention to 61.2% postintervention (p < 0.001) with concomitant reduction in DTN time (median 79 minutes vs 58 minutes, p < 0.001). The resident-delegated task (stroke code to tPA) was reduced (75 minutes vs 44 minutes, p < 0.001), while there was no difference in ED-delegated tasks (door to stroke code [7 minutes vs 6 minutes, p = 0.631], door to CT [18 minutes in both groups, p = 0.547]). There was an increase in stroke mimics treated (6.9% vs 18.4%, p = 0.031), which did not lead to an increase in adverse outcomes. CONCLUSIONS: DTN times were reduced after the implementation of a stroke boot camp and were driven primarily by efficient resident stroke code management. Educational programs should be developed for health care providers involved in acute stroke patient care to improve rapid access to IV tPA at academic institutions.

Quality of life in patients with TIA and minor ischemic stroke.

OBJECTIVE: We investigated health-related quality of life (HRQOL) in patients with TIA and minor ischemic stroke (MIS) using Neuro-QOL, a validated, patient-reported outcome measurement system. METHODS: Consecutive patients with TIA or MIS who had (1) modified Rankin Scale (mRS) score of 0 or 1 at baseline, (2) initial NIH Stroke Scale score of ≤5, (3) no acute reperfusion treatment, and (4) 3-month follow-up, were recruited. Recurrent stroke, disability by mRS and Barthel Index, and Neuro-QOL scores in 5 prespecified domains were prospectively recorded. We assessed the proportion of patients with impaired HRQOL, defined as T scores more than 0.5 SD worse than the general population average, and identified predictors of impaired HRQOL using logistic regression. RESULTS: Among 332 patients who met study criteria (mean age 65.7 years, 52.4% male), 47 (14.2%) had recurrent stroke within 90 days and 41 (12.3%) were disabled (mRS >1 or Barthel Index <95) at 3 months. Any HRQOL impairment was noted in 119 patients (35.8%). In multivariate analysis, age (adjusted odds ratio [OR] 1.02, 95% confidence interval [CI] 1.01-1.04), initial NIH Stroke Scale score (adjusted OR 1.39, 95% CI 1.17-1.64), recurrent stroke (adjusted OR 2.10, 95% CI 1.06-4.13), and proxy reporting (adjusted OR 3.94, 95% CI 1.54-10.10) were independent predictors of impaired HRQOL at 3 months. CONCLUSIONS: Impairment in HRQOL is common at 3 months after MIS and TIA. Predictors of impaired HRQOL include age, index stroke severity, and recurrent stroke. Future studies should include HRQOL measures in outcome assessment, as these may be more sensitive to mild deficits than traditional disability scales.

Do efforts to decrease door-to-needle time risk increasing stroke mimic treatment rates?

An unintended consequence of rapid thrombolysis may be more frequent treatment of stroke mimics, nonvascular conditions that simulate stroke. We explored the relationship between door-to-needle (DTN) times and thrombolysis of stroke mimics at a single academic center by analyzing consecutive quartiles of patients who were treated with IV tissue plasminogen activator for suspected stroke from January 1, 2010 to February 28, 2014. An increase in the proportion of stroke mimic patients (6.7% in each of the 1st and 2nd, 12.9% in the 3rd, and 30% in the last consecutive case quartile; p = 0.03) and a decrease in median DTN time from 89 to 56 minutes (p < 0.01) was found. As more centers reduce DTN times, the rates of stroke mimic treatment should be carefully monitored.

Efficacy and safety of novel oral anticoagulants in patients with cervical artery dissections.

BACKGROUND: American and European guidelines support antiplatelet agents and anticoagulants as reasonable treatments of cervical artery dissection (CAD), though randomized clinical trials are lacking. The utility of novel oral anticoagulants (NOAC), effective in reducing embolic stroke risk in non-valvular atrial fibrillation (NVAF), has not been reported in patients with CAD. We report on the use, safety, and efficacy of NOACs in the treatment of CAD. METHODS: We retrospectively identified patients diagnosed with CAD at a single academic center between January 2010 and August 2013. Patients were categorized by their antithrombotic treatment at hospital discharge with a NOAC (dabigatran, rivaroxaban, or apixaban), traditional anticoagulant (AC: warfarin or treatment dose low-molecular weight heparin), or antiplatelet agent (AP: aspirin, clopidogrel, or aspirin/extended-release dypyridamole). Using appropriate tests, we compared the baseline medical history, presenting clinical symptoms and initial radiographic characteristics among patients in the 3 treatment groups. We then evaluated for the following outcomes: recurrent stroke, vessel recanalization, and bleeding complications. p values <0.05 were considered significant. RESULTS: Of the 149 included patients (mean age 43.4 years; 63.1% female; 70.5% vertebral artery CAD), 39 (26.2%), 70 (47.0%), and 40 (26.8%) were treated with a NOAC, AC, and AP, respectively. More patients with severe stenosis or occlusion were treated with NOAC than with AC or AP (61.8 vs. 60.0 vs. 22.5%, p = 0.002). Other baseline clinical and radiographic findings, including the presence of acute infarction and hematoma, did not differ between the 3 treatment groups. One hundred and thirty-five (90.6%) patients had clinical follow-up (median time 7.5 months) and 125 (83.9%) had radiographic follow-up (median time 5 months) information. There were 2 recurrent strokes in the NOAC group and 1 in each of the AC and AP groups (p = 0.822). There were more major hemorrhagic events in the AC group (11.4%) compared to the NOAC (0.0%) and AP (2.5%) groups (p = 0.034). Three patients treated with NOAC and none treated with AC or AP had a worsened degree of stenosis on follow-up imaging (8.6 vs. 0.0 vs. 0.0%, p = 0.019). CONCLUSION: Compared to traditional anticoagulants for CAD, treatment with NOACs is associated with similar rates of recurrent stroke, fewer hemorrhagic complications, but greater rates of radiographic worsening. These data suggest that NOACs may be a reasonable alternative in the management of CAD. Prospective validation of these findings is needed.

Advances in imaging of intracranial atherosclerotic disease and implications for treatment.

OPINION STATEMENT: Intracranial atherosclerotic disease (ICAD) is one of the most common causes of ischemic stroke worldwide and is associated with a high risk of recurrent stroke despite aggressive therapy. ICAD may lead to cerebral ischemia through a variety of mechanisms, the interactions of which are largely unknown. The use of endovascular therapy for the prevention of stroke related to severe ICAD has been studied but was associated with a higher risk of recurrent stroke and death in the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) study. With advances in diagnostic testing, it may be possible to better delineate the specific mechanism of stroke from ICAD and identify those patients at higher risk for recurrent ischemia. There may be a subset of patients less responsive to medical interventions, such as those with hemodynamic failure as opposed to those with perforator syndromes, who would benefit from medical plaque stabilization or safer endovascular approaches such as angioplasty alone. These will need to be tested in future clinical trials. Overall, symptomatic ICAD remains a high risk condition with suboptimal treatment options.

Leukoaraiosis on magnetic resonance imaging correlates with worse outcomes after spontaneous intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Leukoaraiosis (LA) is associated with dementia, ischemic stroke, and intracerebral hemorrhage (ICH), but there are few data on how LA might impact outcomes after acute ICH. We tested the hypothesis that the severity of LA on magnetic resonance imaging is related to worse functional outcomes after spontaneous ICH. METHODS: We prospectively identified patients with spontaneous acute ICH. LA was identified on magnetic resonance imaging and its severity was graded using the Fazekas method to include a score for the deep white matter and periventricular regions. Outcomes were obtained at 14 days, 28 days, and 3 months with the modified Rankin Scale (mRS; a validated scale from 0 [no symptoms] to 6 [dead]) and analyzed with multivariate logistic regression. RESULTS: Higher Fazekas total (periventricular plus deep white matter) score correlated with higher mRS score at 14 days (P=0.02) and 3 months (P=0.02). This relationship was driven by the periventricular score, for which higher score (more severe disease) correlated with higher National Institute of Health Stroke Scale at 14 days (P=0.03), and higher mRS score at 14 days (P<0.001), 28 days (P=0.004), and 3 months (P=0.005). A higher (more severe) Fazekas periventricular score was associated with dependence or death at 3 months (odds ratio, 1.8 per point; 95% confidence interval, 1.02-3.1; P=0.04) after correction for the ICH score. CONCLUSIONS: Increased LA is an independent predictor of worse functional outcomes in patients after spontaneous ICH. The pathophysiology associating LA with worse outcomes requires further study. These data may improve prognostication and selection for clinical trials.