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To extend the MR MultiTasking-based Multidimensional Assessment of Cardiovascular System (MT-MACS) technique with larger spatial coverage and water-fat separation for comprehensive aortocardiac assessment.MT-MACS adopts a low-rank tensor image model for 7D imaging, with three spatial dimensions for volumetric imaging, one cardiac motion dimension for cine imaging, one respiratory motion dimension for free-breathing imaging, one T2-prepared inversion recovery time dimension for multi-contrast assessment, and one T2*-decay time dimension for water-fat separation. Nine healthy subjects were recruited for the 3T study. Overall image quality was scored on bright-blood (BB), dark-blood (DB), and gray-blood (GB) contrasts using a 4-point scale (0-poor to 3-excellent) by two independent readers, and their interreader agreement was evaluated. Myocardial wall thickness and left ventricular ejection fraction (LVEF) were quantified on DB and BB contrasts, respectively. The agreement in these metrics between MT-MACS and conventional breath-held, electrocardiography-triggered 2D sequences were evaluated.MT-MACS provides both water-only and fat-only images with excellent image quality (average score = 3.725/3.780/3.835/3.890 for BB/DB/GB/fat-only images) and moderate to high interreader agreement (weighted Cohen's kappa value = 0.727/0.668/1.000/1.000 for BB/DB/GB/fat-only images). There were good to excellent agreements in myocardial wall thickness measurements (intraclass correlation coefficients [ICC] = 0.781/0.929/0.680/0.878 for left atria/left ventricle/right atria/right ventricle) and LVEF quantification (ICC = 0.716) between MT-MACS and 2D references. All measurements were within the literature range of healthy subjects.The refined MT-MACS technique provides multi-contrast, phase-resolved, and water-fat imaging of the aortocardiac systems and allows evaluation of anatomy and function. Clinical validation is warranted.

Background: Although chronic kidney disease (CKD) is associated with worse stroke outcomes, data regarding the influence of CKD on intravenous thrombolysis outcomes are scarce. We sought to assess the efficacy and safety of intravenous thrombolysis for acute ischemic stroke with unknown onset time in patients with CKD. Methods: Patients with an acute stroke of unknown onset time from the EOS trials (Evaluation of Unknown Onset Stroke Thrombolysis) collaboration were evaluated using an individual patient-level database of randomized controlled trials comparing intravenous thrombolysis with placebo/standard treatment. CKD was defined as baseline estimated glomerular filtration rate of 2 Mixed-effect logistic-regression analysis was performed to evaluate treatment effects. A favorable outcome was defined as a modified Rankin Scale score of 0 to 1 at 90 days. Safety outcomes were symptomatic intracranial hemorrhage at 22 to 36 hours and 90-day mortality. Results: Baseline data on renal function were available for 688 of 843 patients. Of these, CKD was present in 146 (21%), including 69 of 351 patients receiving alteplase and 77 of 337 patients receiving placebo/standard treatment. Overall, treatment with alteplase was associated with higher odds of favorable outcome, and CKD did not modify the treatment effect ( P interaction =0.834). A favorable outcome was observed in 31 of 69 (46%) patients with CKD in the alteplase group and in 28 of 77 (36%) patients with CKD in the control group (adjusted odds ratio, 1.19 [95% CI, 0.55–2.58]). Among patients with CKD, symptomatic intracranial hemorrhage occurred in 2 patients (3%) in the alteplase group but in none of the controls ( P =0.133). At 90 days, death was reported in 3 patients (4%) in the alteplase group compared with 2 patients (3%) in the controls ( P =0.539). Conclusions: The present analysis indicates that the benefit of alteplase does not differ between stroke patients with unknown onset time with and without CKD, although the statistical power was lacking to confirm the efficacy in subgroups. This study only applies to mild-to-moderate or predialysis CKD.

Background: Race and ethnicity can have a major impact on the quality of care patients with acute ischemic stroke (AIS) receive. We sought to assess the impact of race and ethnicity on quality benchmarks of AIS therapy and clinical outcomes at a comprehensive stroke center (CSC). Methods: A retrospective analysis of AIS patients presenting to a CSC between 2015 to 2020 was performed. Data included demographics, NIH Stroke Scale scores, time to thrombolysis, discharge diabetic and hypertensive medications, length of stay (LOS), discharge functional status, 30-day readmission, and 30-day mortality. Quality benchmarks and outcomes were analyzed by the five most prevalent racial-ethnic groups including Non-Hispanic White (NHW), Hispanic, Black, Asian, Other and Unknown. Results: 3,735 AIS patients were identified. NHW represented 53.3% (n=1992),Black 21.3% (n=797), Hispanic 10.4% (n=390), Asian 7.2% (n=267), Other 4.6% (n=170) and Unknown 3.2% (n=119). There were no significant differences in door to needle (P=0.93), door to puncture time (P=0.98), intravenous thrombolysis (P=0.32) and mechanical thrombectomy utilization (P=0.19) by race-ethnicity. In univariable analysis, there was a higher rate of 30-day mortality in Unknown 23.5% vs NHW 7.3% (P< 0.0001). A significantly (P>0.05) higher rate of 30-day readmission was noted in NHW 20.3% vs Black 15.7%, Hispanics 15.6%, Others 11.8% and Unknown 8.4%. Black 67.6%, Hispanic 64.9% and Unknown 80.5% had a significantly (P2) vs NHW 60.3%. A significant difference (P Conclusions: Our analysis reveals persistent disparities in stroke outcomes, with Black and Hispanic patients suffering greater disability post stroke. Further investigation is needed to uncover how race-ethnicity mediates stroke care and outcomes.

Introduction: The determinants of fast and slow progressor phenotypes of infarct growth in anterior circulation large vessel occlusion (ACLVO) remain poorly understood. Previous studies have shown a potential link between baseline serum glucose and acute infarct growth. We assessed whether presenting serum glucose is independently associated with fast or slow progression of infarct growth in ACLVO stroke. Methods: Retrospective analysis of patients with acute stroke due to intracranial ICA or proximal MCA occlusion across two comprehensive stroke centers from 2014-2019. Baseline CTP or MRI were obtained within 24hours of stroke onset. Fast progressors (ischemic core > 70ml, 0-6 h) and slow progressors ( Results: A total of 350 participants were included (n=178 imaged < 6 hours of stroke onset; n=172 imaged at 6-24 hours of stroke onset). Amongst early presenters, the median glucose was 127 mg/dL for fast progressors (n=32) versus 122 mg/dL in non-fast progressors (n=146), p=0.45. Amongst late presenters, the median glucose was 122 mg/dL for slow progressors versus 133 in non-slow progressors (p=0.085). The correlation between serum glucose concentration and infarct growth rate was 0.03 (p=0.57). Conclusion: While a numerical trend suggesting lower glucose levels was observed in slow progressors, no significant correlation between hyperacute serum glucose and infarct growth rate was established.

Background: Language barriers can have a major impact on the quality of care that patients with acute ischemic stroke (AIS) receive. We sought to assess the impact of patient language on quality benchmarks of AIS therapy and clinical outcomes at a high-volume comprehensive stroke center (CSC). Methods: A retrospective analysis of AIS patients presenting to a CSC between 2015 to 2020 was performed. Data included demographics, NIH Stroke Scale scores (NIHSS), discharge diabetic and hypertensive medications, length of stay (LOS), discharge functional status, 30-day readmission, and 30-day mortality. Quality benchmarks and outcomes were analyzed by the five most prevalent primary languages including English, Spanish, Russian, Farsi, Korean and Other. All non-English speaking patients received medical interpretation via digital or in-person translation. Results: 3,812 AIS patients were identified. English language represented 80.2% (n=3091), Spanish 7.6% (n=238), Russian 4.1% (n=184), Farsi 3.0% (n=129), Korean 1.5% (n=47) and Other 3.6% (n=122).There were no significant differences in the rate of intravenous thrombolysis (P=0.52), door-to-needle time (P=0.91), door-to-puncture time (P=0.85), LOS (P=0.089) and 30 day readmission (P=0.74) among groups. In univariable analysis, Spanish 74.7%, Korean 84.4%, Russian 73.4%, Farsi 78.2% and Other 70.0% had significantly (P< 0.05) higher rates of post stroke disability (mRS> 2) compared to the English group 60.7%. A higher rate of 30-day mortality was noted in the Korean 17.8% compared to the English group 7.3%. The Spanish group had a higher rate of mechanical thrombectomy than the English group (11.8 vs 6.5%, P=0.009). Adjusting for age, sex, NIHSS and comorbidities, multivariable logistic regression models for post stroke disability (mRS>2) continued to show significant differences with Spanish (OR=1.66, P=0.008) and Farsi (OR=1.89, P=0.017) vs English. Conclusions: Our analysis reveals persistent disparities in AIS outcomes by primary language, with patients with limited English proficiency suffering worse disability after AIS. The effect of communication barriers on outcomes of stroke care in the inpatient setting requires further evaluation to close this gap.

Introduction: Endovascular therapy is a treatment option for patients with severe symptomatic intracranial atherosclerotic disease (ICAD). The utilization of angioplasty and stenting has varied since the development of stents for this disease in 2005. This study assesses the longitudinal trends for endovascular treatment of ICAD in the U.S. Methods: We performed a data search from the National Inpatient Sample (NIS) database using ICD9 and ICD10 procedure codes from 2008 through 2019. Data was collected for patients with stroke from ICAD who underwent stenting or angioplasty alone. We also assessed the utilization of stenting or angioplasty in thrombectomy cases for large vessel occlusion (LVO), the use of drug eluting stents, patient demographics, regional trends, length of stay, and mortality statistics. Results: Between 2008 and 2019, the nadir of ICAD stenting cases in the U.S. was in 2011 (n=242). There was over a 207% increase in stenting cases in 2015 (n=730), and another increase of 47% in ICAD stenting in 2018 and 2019 (2018=965, 2019=1,175). There was a significant increase in stenting for ICAD over the entire study period (p=0.003). The data also shows a significant increase in the use of stenting as adjunctive therapy to thrombectomy for LVO. In 2011, stenting with thrombectomy in LVO represented 17.8% (43/242) of patients stented with stroke from ICAD. In 2019, these cases represented 48.1% (565/1,175) of the patients stented. Over the study period, this increase in stent use during LVO treatment was significant (p Conclusion: There has been a progressive increase in stenting for ICAD since the nadir of this procedure in 2011 which is statistically significant. This increase was seen in patients with severe symptomatic ICAD, but also in patients undergoing thrombectomy for acute LVO with ICAD. Positive clinical stenting trials such as WEAVE and the post-hoc analysis from SAMMPRIS, and the increase in endovascular therapy for LVO appear temporally related to these changes.

Purpose The trend of atherosclerotic plaque feature evolution is unclear in stroke patients with and without recurrence. We aimed to use three-dimensional whole-brain magnetic resonance vessel wall imaging to quantify the morphological changes of causative lesions during medical therapy in patients with symptomatic intracranial atherosclerotic disease. Methods Patients with acute ischemic stroke attributed to intracranial atherosclerotic disease were retrospectively enrolled if they underwent both baseline and follow-up magnetic resonance vessel wall imaging. The morphological features of the causative plaque, including plaque volume, peak normalized wall index, maximum wall thickness, degree of stenosis, pre-contrast plaque-wall contrast ratio, and post-contrast plaque enhancement ratio, were quantified and compared between the non-recurrent and recurrent groups (defined as the recurrence of a vascular event within 18 months of stroke). Results Twenty-nine patients were included in the final analysis. No significant differences were found in plaque features in the baseline scan between the non-recurrent ( n = 22) and recurrent groups ( n = 7). The changes in maximum wall thickness (–13.32% vs. 8.93%, P = 0.026), plaque-wall contrast ratio (–0.82% vs. 3.42%, P = 0.005) and plaque enhancement ratio (–11.03% vs. 9.75%, P = 0.019) were significantly different between the non-recurrent and recurrent groups. Univariable logistic regression showed that the increase in plaque-wall contrast ratio (odds ratio 3.22, 95% confidence interval 1.55–9.98, P = 0.003) was related to stroke recurrence. Conclusion Morphological changes of plaque features on magnetic resonance vessel wall imaging demonstrated distinct trends in symptomatic intracranial atherosclerotic disease patients with and without stroke recurrence.

Objective: To describe the impact of COVID-19 on acute cerebrovascular disease care across 9 comprehensive stroke centers throughout Los Angeles County (LAC). Methods: Volume of emergency stroke code activations, patient characteristics, stroke severity, reperfusion rates, treatment times, and outcomes from February 1 to April 30, 2020, were compared against the same time period in 2019. Demographic data were provided by each participating institution. Results: There was a 17.3% decrease in stroke code activations across LAC in 2020 compared to 2019 (1,786 vs. 2,159, respectively, χ2 goodness of fit test p < 0.0001) across 9 participating comprehensive stroke centers. Patients who did not receive any reperfusion therapy decreased by 16.6% in 2020 (1,527) compared to 2019 (1,832). Patients who received only intravenous thrombolytic (IVT) therapy decreased by 31.8% (107 vs. 157). Patients who received only mechanical thrombectomy (MT) increased by 3% (102 vs. 99). Patients who received both IVT and MT decreased by 31.8% (45 vs. 66). Recanalization treatment times in 2020 were comparable to 2019. CSCs serving a higher proportion of Latinx populations in the eastern parts of LAC experienced a higher incidence of MT in 2020 compared to 2019. Mild increase in stroke severity was seen in 2020 compared to 2019 (8.95 vs. 8.23, p = 0.046). A higher percentage of patients were discharged home in 2020 compared to 2019 (59.5 vs. 56.1%, p = 0.034), a lower percentage of patients were discharged to skilled nursing facility (16.1 vs. 20.7%, p = 0.0004), and a higher percentage of patients expired (8.6 vs. 6.3%, p = 0.008). Conclusion: LAC saw a decrease in overall stroke code activations in 2020 compared to 2019. Reperfusion treatment times remained comparable to prepandemic metrics. There has been an increase in severe stroke incidence and higher volume of thrombectomy treatments in Latinx communities within LAC during the pandemic of 2020. More patients were discharged home, less patients discharged to skilled nursing facilities, and more patients expired in 2020, compared to the same time frame in 2019.

Background and aims Intracranial atherosclerotic disease (ICAD) is a major etiologic cause for acute ischemic stroke (AIS) and transient ischemic attack (TIA). The study was designed to investigate if differential morphological features exist in symptomatic atherosclerotic lesions between AIS and TIA patients. Methods The culprit plaques from 45 AIS patients and 42 TIA patients were analyzed for the degree of stenosis, vessel wall irregularity, normalized wall index (NWI), remodeling index, plaque-wall contrast ratio (CR), high signal intensity on T1-weighted images, plaque enhancement ratio and enhancement grade. These plaque features along with clinical characteristics were compared between AIS and TIA groups as well as between their stenosis degree-matched subgroups. Results Overall, grade 2 enhancement (OR 3.85, 95%CI 1.42–10.46, p = 0.006) and hyperlipidemia (OR 3.04, 95%CI 1.13–8.22, p = 0.025) were independent indicators for AIS, whereas high NWI (OR 1.47, 95%CI 0.76–2.86, p = 0.004) was associated with TIA. In the comparison between the subgroups with moderate (30%–69%) stenosis, high plaque-wall CR (OR 5.38, 95%CI 1.39–20.75, p = 0.008) was associated with AIS, whereas high NWI (OR 2.50, 95%CI 0.61–10.00, p = 0.006) was associated with TIA. Conclusions Our study reveals differential morphological features in symptomatic ICAD lesions between AIS and TIA patients. Probing these features with MR vessel wall imaging may provide insights into the prognosis of patients with ICAD.

INTRODUCTION We aim to report 3 cases of central nervous system (CNS) vasculitides, in which high-resolution magnetic resonance vessel wall imaging (HR-VWI) findings were instrumental in the diagnosis and management. CASE REPORT Case 1: A 41-year-old obese, smoker female with arterial hypertension presented with recurrent transient ischemic attacks. Computed topography angiography demonstrated bilateral middle cerebral artery (MCA) stenosis. HR-VWI revealed uniform enhancement and thickening of the arterial wall, suggestive of MCA vasculitis. The patient reported chronic calf rash that was biopsied and revealed unspecified connective tissue disease. With immunomodulation, patient remained asymptomatic and 6-month surveillance HR-VWI showed improved MCA stenoses.Case 2: A 56-year-old male with herpes simplex virus 1 encephalitis was treated with antiviral therapy and improved clinically. Two months later, the brain magnetic resonance imaging revealed new temporo-parietal edema and distal MCA hyperintense vessels. HR-VWI showed MCA concentric smooth contrast enhancement, that was attributed to postinfectious vasculitis and had resolved on follow-up HR-VWI.Case 3: A 41-year-old male presented with 1-week of headache and encephalopathy. Brain magnetic resonance imaging revealed punctate multifocal acute ischemic infarcts and no contrast-enhancement. HR-VWI showed multifocal diffuse enhancement of distal cerebral vasculature. Patient subsequently developed branch retinal artery occlusion and hearing loss and was diagnosed with Susac syndrome. No recurrent symptoms were noted after immunotherapy initiation. CONCLUSIONS In these 3 cases, HR-VWI identified distinctive vascular inflammatory changes, which were crucial to guide the etiological workup, positive diagnosis, surveillance neuroimaging, and targeted treatment. HR-VWI is an important diagnostic tool in CNS vasculitides, by providing nuanced information about arterial wall integrity and pathology.

Introduction: Despite pharmacological and practical advantages for tenecteplase (TNK) over alteplase (ALT), no differences were observed in percent of symptomatic intracranial hemorrhage (sICH) in randomized trials (fewer than 900 total patients for either treatment). We compared rates of sICH in patients treated with either drug, using a large, multicenter, international registry. Methods: The CERTAIN collaboration is an ongoing registry of deidentified patient-level data of thrombolytic treated ischemic stroke from various hospitals/programs in New Zealand, Australia, and the United States that have used ALT or TNK since July 1, 2018. Standardized data were abstracted and harmonized from local or regional clinical registries. We defined sICH as clinical worsening of at least 4 points on NIHSS, attributed to parenchymal hematoma, subarachnoid or intraventricular hemorrhage. We used logistic regression for binary variables, adjusting sICH differences for age, baseline NIHSS, thrombectomy, and source hospital network and Mann-Whitney test for continuous baseline variables. Results: A total of 7891 patients were included in the initial analysis. The TNK group was older, more likely to be male, had higher NIHSS, and more frequently underwent mechanical thrombectomy (Table. Sample Characteristics). The sICH rate was 3.71% for ALT and 2.13% for TNK: adjusted OR (95%CI) = 0.49 (0.31-0.76) p=0.002. For patients not undergoing thrombectomy after thrombolytic, the sICH rate was 3.00% for ALT and 1.74% for TNK, adjusted OR (95%CI) = 0.48 (0.27-0.87), p=0.016. For thrombectomy treated cases, sICH rate was 6.80% for ALT and 2.80% for TNK, adjusted OR (95%CI) 0.60 (0.31-1.16), p=0.129. Conclusion: In this preliminary analysis from a large, multicenter registry, ischemic stroke treated with tenecteplase was associated with a lower rate of sICH than with alteplase. An updated analysis with patient data from additional sites will be presented at the Conference.

International audience; BACKGROUND: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. METHODS: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0-1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0-2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4-6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. FINDINGS: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10-2·03]; p=0·011), with low heterogeneity across studies (I(2)=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05-1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06-2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4-6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52-1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03-4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [\textless1%], adjusted OR 5·58 [1·22-25·50]; p=0·024). INTERPRETATION: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death. FUNDING: None.

Background Intracranial atherosclerotic disease (ICAD) is one of the most challenging stroke etiologies, with frequent recurrences despite optimized medical management. Encephaloduroarteriosynangiosis (EDAS) is an indirect revascularization method that produces extra-cranial collaterals to intracranial vessels. We present the results of a phase-II trial of EDAS in intracranial atherosclerotic disease patients. Aims To evaluate the feasibility, safety, and preliminary efficacy of EDAS in intracranial atherosclerotic disease patients. Methods ERSIAS was a prospective objective-performance-criterion trial of EDAS plus intensive medical management (IMM) in intracranial atherosclerotic disease (ICAD) patients failing medical treatment. Primary endpoint was any stroke/death within 30-days post-surgery or stroke in the territory of the qualifying artery beyond 30 days. The primary analysis compared event rates through one year with an objective-performance-criterion based on a 10% reduction from the 20% rate in the intensive medical management arm of the stenting versus aggressive medical management for preventing recurrent stroke in intracranial stenosis trial (SAMMPRIS) in patients with poor collaterals. Event rates through two years were compared with propensity-score-matched (PSM) medically treated patients from SAMMPRIS and the carotid occlusion surgery study (COSS). Results During a median follow-up of 24.5 months, 5 (9.6%) of 52 patients had a primary endpoint event. The primary endpoint rate at one year met the threshold for nonfutility and advancement to phase III (Conclusion ERSIAS phase II provides evidence of safety and strong signals of efficacy of EDAS-plus-intensive medical management, supporting advancement to a seamless phase-IIb/III trial. Clinical Trial Registration URL: https://www.clinicaltrials.gov.NCT01819597 .

The coronavirus disease 2019 pandemic has changed the way we engage patient care, with a move toward telemedicine-based health care encounters. Teleneurology is now being rapidly embraced by neurologists in clinics and hospitals nationwide but for many, this paradigm of care is unfamiliar. Exposure to telemedicine in neurology training programs is scarce despite previous calls to expand teleneurology education. Programs that provide a teleneurology curriculum have demonstrated increased proficiency, accuracy, and post-training utilization among their trainees. With the current changes in health care, broad incorporation of teleneurology education in resident and fellow training after this pandemic dissipates will only serve to improve trainee preparedness for independent practice.

PURPOSE To develop an MR multitasking-based multidimensional assessment of cardiovascular system (MT-MACS) with electrocardiography-free and navigator-free data acquisition for a comprehensive evaluation of thoracic aortic diseases. METHODS The MT-MACS technique adopts a low-rank tensor image model with a cardiac time dimension for phase-resolved cine imaging and a T2 -prepared inversion-recovery dimension for multicontrast assessment. Twelve healthy subjects and 2 patients with thoracic aortic diseases were recruited for the study at 3 T, and both qualitative (image quality score) and quantitative (contrast-to-noise ratio between lumen and wall, lumen and wall area, and aortic strain index) analyses were performed in all healthy subjects. The overall image quality was scored based on a 4-point scale: 3, excellent; 2, good; 1, fair; and 0, poor. Statistical analysis was used to test the measurement agreement between MT-MACS and its corresponding 2D references. RESULTS The MT-MACS images reconstructed from acquisitions as short as 6 minutes demonstrated good or excellent image quality for bright-blood (2.58 ± 0.46), dark-blood (2.58 ± 0.50), and gray-blood (2.17 ± 0.53) contrast weightings, respectively. The contrast-to-noise ratios for the three weightings were 49.2 ± 12.8, 20.0 ± 5.8 and 2.8 ± 1.8, respectively. There were good agreements in the lumen and wall area (intraclass correlation coefficient = 0.993, P < .001 for lumen; intraclass correlation coefficient = 0.969, P < .001 for wall area) and strain (intraclass correlation coefficient = 0.947, P < .001) between MT-MACS and conventional 2D sequences. CONCLUSION The MT-MACS technique provides high-quality, multidimensional images for a comprehensive assessment of the thoracic aorta. Technical feasibility was demonstrated in healthy subjects and patients with thoracic aortic diseases. Further clinical validation is warranted.

Background and purpose Mechanical circulatory support (MCS) devices are commonly used in heart failure patients. These devices carry risk for presumably embolic and additionally hemorrhagic stroke. Alterations in blood flow play a key role in stroke pathophysiology, and we aimed to learn more about hemodynamic compromise. In this study, we used transcranial Doppler (TCD) ultrasound to define hemodynamics of commonly used nonpulsatile MCS devices, as well as pulsatile devices, with special attention to the total artificial heart (TAH). Methods From 2/2013 through 12/2016, we prospectively enrolled patients with MCS who underwent TCD imaging. We analyzed TCD parameters, including peak systolic velocity, end-diastolic velocity, pulsatility indices (PIs), and number of high-intensity transient signals. Waveform morphologies were compared between various MCS devices. Results We performed 132 TCD studies in 86 MCS patients. Waveforms in patients supported by venoarterial-extracorporeal membrane oxygenation demonstrated continuous flow without clear systolic peaks with an average (±SD) PI of .43 (±.2). PIs were low in patients with continuous-flow left ventricular assist devices with a mean PI of .32 (±.13). Impella patients had morphologically distinct pulsatile waveforms and a higher mean PI of .65 (±.24). In intra-arterial balloon pump patients, mean PI was 1.01 (±.16) and diastolic upstrokes were pronounced. In TAH patients, mean middle cerebral artery velocity of 79.69 (±32.33) cm/seconds and PI of .74 (±.14) approached normal values. Conclusion TCD can detect characteristic waveforms in patients supported by various MCS devices. These device-specific TCD patterns are recognizable and reproducible.

Intracranial atherosclerotic disease (ICAD) is a common cause of stroke with high rates of ischemic recurrence. We aimed to investigate the role of circulating exosomal microRNAs (e-miRNAs) in recurrent ischemic events in ICAD. Consecutive patients with severe ICAD undergoing intensive medical management (IMM) were prospectively enrolled. Those with recurrent ischemic events despite IMM during 6-month follow up were algorithmically matched to IMM responders. Baseline blood e-miRNA expression levels of the matched patients were measured using next generation sequencing. A total of 122 e-miRNAs were isolated from blood samples of 10 non-responders and 11 responders. Thirteen e-miRNAs predicted IMM failure with 90% sensitivity and 100% specificity. Ingenuity pathway analysis (IPA) determined 10 of the 13 e-miRNAs were significantly associated with angiogenesis-related biological functions (p

Background Vascular endothelial growth factor-A165 (VEGF-A165) has been identified as a combination of 2 alternative splice variants: proangiogenic VEGF-A165a and antiangiogenic VEGF-A165b. Intracranial atherosclerotic disease (ICAD) and moyamoya disease (MMD) are 2 main types of intracranial arterial steno-occlusive disorders with distinct capacities for collateral formation. Recent studies indicate that VEGF-A165 regulates collateral growth in ischemia. Therefore, we investigated if there is a distinctive composition of VEGF-A165 isoforms in ICAD and MMD. Methods Sixty-six ICAD patients, 6 MMD patients, and 5 controls were enrolled in this prospective study. ICAD and MMD patients received intensive medical management upon enrollment. Surgery was offered to 9 ICAD patients who had recurrent ischemic events, 6 MMD patients, and 5 surgical controls without ICAD. VEGF-A165a and VEGF-A165b plasma levels were measured at baseline, within 1 week after patients having surgery, and at 1, 3, and 6 months after treatment. Results A significantly higher baseline VEGF-A165a/b ratio was observed in MMD compared to ICAD (P = .016). The VEGF-A165a/b ratio increased significantly and rapidly after surgical treatment in ICAD (P = .026) more so than in MMD and surgical controls. In patients with ICAD receiving intensive medical management, there was also an elevation of the VEGF-A165a/b ratio, but at a slower rate, reaching the peak at 3 months after initiation of treatment (baseline versus 3 months VEGF-A165a/b ratio, P = .028). Conclusions Our study shows an increased VEGF-A165a/b ratio in MMD compared to ICAD, and suggests that both intensive medical management and surgical revascularization elevate the VEGF-A165a/b ratio in ICAD patients.

Objective Agonism of protease-activated receptor (PAR) 1 by activated protein C (APC) provides neuro- and vasculoprotection in experimental neuroinjury models. The pleiotropic PAR1 agonist, 3K3A-APC, reduces neurological injury and promotes vascular integrity; 3K3A-APC proved safe in human volunteers. We performed a randomized, controlled, blinded trial to determine the maximally tolerated dose (MTD) of 3K3A-APC in ischemic stroke patients. Methods The NeuroNEXT trial, RHAPSODY, used a novel continual reassessment method to determine the MTD using tiers of 120, 240, 360, and 540 μg/kg of 3K3A-APC. After intravenous tissue plasminogen activator, intra-arterial mechanical thrombectomy, or both, patients were randomized to 1 of the 4 doses or placebo. Vasculoprotection was assessed as microbleed and intracranial hemorrhage (ICH) rates. Results Between January 2015 and July 2017, we treated 110 patients. Demographics resembled a typical stroke population. The MTD was the highest-dose 3K3A-APC tested, 540 μg/kg, with an estimated toxicity rate of 7%. There was no difference in prespecified ICH rates. In exploratory analyses, 3K3A-APC reduced ICH rates compared to placebo from 86.5% to 67.4% in the combined treatment arms (p = 0.046) and total hemorrhage volume from an average of 2.1 ± 5.8 ml in placebo to 0.8 ± 2.1 ml in the combined treatment arms (p = 0.066). Interpretation RHAPSODY is the first trial of a neuroprotectant for acute ischemic stroke in a trial design allowing thrombectomy, thrombolysis, or both. The MTD was 540 μg/kg for the PAR1 active cytoprotectant, 3K3A-APC. A trend toward lower hemorrhage rate in an exploratory analysis requires confirmation. Clinical trial registration Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT02222714. ANN NEUROL 2019;85:125-136.

The purpose of this article is to address several challenging questions in the management of young patients (those age 60 and under) who present with ischemic stroke. Do genetic thrombophilic states, strongly associated with venous thrombosis, independently cause arterial events in adults? Should cases of patent foramen ovale be closed with mechanical devices in patients with cryptogenic stroke? What are the optimal treatments for cerebral vein thrombosis, carotid artery dissection, and antiphospholipid syndrome and are DOACs acceptable treatment for these indications? What is the mechanism underlying large vessel stroke in patients with COVID-19? This is a narrative review. We searched PubMed and Embase and American College of physicians Journal club database for English language articles since 2000 looking mainly at randomized clinical trials, Meta analyses, Cochran reviews as well as some research articles viewed to be cutting edge regarding anticoagulation and cerebrovascular disease. Searches were done entering cerebral vein thrombosis, carotid dissection, anticoagulation therapy and stroke, antiphospholipid antibody and stroke, stroke in young adults, cryptogenic stroke and anticoagulation, patent foramen ovale and cryptogenic stroke, COVID-19 and stroke.

Background: Acute stroke care is constantly evolving and often necessitates rapid change. When COVID-19 struck our community, our team determined that we needed to change our approach to emergent stroke cases without sacrificing efficiency and safety. Our goals with the changes in our hyperacute stroke response pathway (called Code Brain) in our ED was to minimize COVID-19 exposure to our team, reduce PPE usage, and maintain an environment of safety and readiness, all while providing the same high-quality stroke care. Purpose: The purpose of this study was to determine if the changes we made to our Code Brain pathway in the ED effected our door-to-needle time for tissue plasminogen activator (t-PA) administration our door-to-groin puncture (DTG) times, or our CT scan turn-around times (CT TAT) under 45 minutes percentage. Implementation: It was decided that the stroke team RNs would respond to the bedside and a neurology resident or fellow would respond via telemedicine robot at bedside. The stroke team nurse is the safety monitor who ensures proper PPE use. The patient is moved through the Code Brain pathway with the telemedicine robot in tow, assuring constant contact with the patient by the stroke physician and stroke nurse. We implemented our revised Code Brain pathway on March 17, 2020. We retrospectively collected data from November 2019 to July 2020 and extracted our DTN, DTG and CT TAT times for a 4 ½ month comparison. Results: From November 2019 through March 17, 2020, our DTN median time was 39 minutes, DTG median time was 101 minutes, and CT TAT under 45 minutes was 97%. From March 18, 2020 to July 2020, our DTN median time was 54 minutes, DTG median time was 101 minutes, and CT TAT under 45 minutes was 95%. Variables to consider are the length of time it takes to apply the appropriate PPE for the stroke nurse, obtaining the telemedicine robot from our ED storage area and connectivity issues. Conclusion: Although we radically changed the way we approach our Code Brain patients, our response and treatment times changed only slightly. We will continue to streamline this process for optimal outcomes.

Introduction: Exposure to telestroke in neurology residency is sparse despite its implementation in daily practice. Due to COVID-19, we increased our utilization of telestroke. Given this change in workflow, we investigated how residents utilize telestroke for “Code Brain” (CB) acute stroke evaluations and if expanding the use of telestroke in neurology residency programs is justified. Methods: We retrospectively compared the number of CB evaluations, door to needle (DTN) times, door to decision (DTD) times, and NIHSS from March - June 2019 (in-person evaluations) against those in March - June 2020 (telestroke evaluations). We limited our study to resident-involved cases. Nighttime and weekend CBs are run by a neurology resident and are remotely supervised. Daytime CBs can be run by a resident, fellow, or attending. We assumed that nighttime CBs are resident-run and daytime evaluations are the stroke team’s evaluation. Statistical analysis was performed using R. Results: There were a total of 217 CBs in March - June 2019 and 115 in March - June 2020. In 2019, there were 120 daytime and 97 nighttime CBs; in 2020 there were 62 and 53. The mean DTN for the day for 2019 and 2020 was 45.9 ± 23.2 and 48.4 ± 20.2 (P=0.08). The mean DTN during the night for 2019 and 2020 was 67.3 ± 53.7 and 53.8 ± 25.8 (P=0.64). The mean DTD during the day for 2019 and 2020 was 48.1 ± 41.0 and 44.9 ± 37.6 (P=0.25). The mean DTD during the night for 2019 and 2020 was 60.9 ± 51.1 and 65.8 ± 94.6 (P=0.68). Using a generalized linear model approach to correct for shift (day/night), age, NIHSS, we found no significant differences in DTN or DTD before and after implementing resident-run telestroke. Using Cohen’s approach (1988) we estimated a Type 2 error probability at 7%. Discussion: Our findings show that resident-run telestroke CBs are comparable to CBs run by fellows and attendings as DTN and DTD were not significantly different between the CBs run by residents in-person or via telestroke. These metrics are also comparable for CBs in which a fellow or attending are supervising or running the CB. Implementing resident-run telestroke consultation showed no effect on DTN or DTD after accounting for patient age, NIHSS, or the time of day. These data should reassure programs seeking to grant telestroke privileges to trainees.

Key Points Question Is a team-based community health worker and advanced practice clinician (including nurse practitioners or physician assistants) intervention emphasizing evidence-based care, self-management, lifestyle change, and medication adherence superior to usual care for controlling blood pressure after stroke in safety-net settings? Findings In this randomized clinical trial that included 487 adults with recent stroke or transient ischemic attack, there was no difference between usual care and the multifaceted team-based intervention in blood pressure control at 12 months. Meaning These findings suggest that additional research is needed to determine the optimal care model for controlling risk factors after stroke in safety-net settings., This randomized clinical trial examines the effect of a multifaceted team intervention vs usual care on systolic blood pressure (SBP) among patients with stroke or transient ischemic attack (TIA) in safety-net settings., Importance Few stroke survivors meet recommended cardiovascular goals, particularly among racial/ethnic minority populations, such as Black or Hispanic individuals, or socioeconomically disadvantaged populations. Objective To determine if a chronic care model–based, community health worker (CHW), advanced practice clinician (APC; including nurse practitioners or physician assistants), and physician team intervention improves risk factor control after stroke in a safety-net setting (ie, health care setting where all individuals receive care, regardless of health insurance status or ability to pay). Design, Setting, and Participants This randomized clinical trial included participants recruited from 5 hospitals serving low-income populations in Los Angeles County, California, as part of the Secondary Stroke Prevention by Uniting Community and Chronic Care Model Teams Early to End Disparities (SUCCEED) clinical trial. Inclusion criteria were age 40 years or older; experience of ischemic or hemorrhagic stroke or transient ischemic attack (TIA) no more than 90 days prior; systolic blood pressure (BP) of 130 mm Hg or greater or 120 to 130 mm Hg with history of hypertension or using hypertensive medications; and English or Spanish language proficiency. The exclusion criterion was inability to consent. Among 887 individuals screened for eligibility, 542 individuals were eligible, and 487 individuals were enrolled and randomized, stratified by stroke type (ischemic or TIA vs hemorrhagic), language (English vs Spanish), and site to usual care vs intervention in a 1:1 fashion. The study was conducted from February 2014 to September 2018, and data were analyzed from October 2018 to November 2020. Interventions Participants randomized to intervention were offered a multimodal coordinated care intervention, including hypothesized core components (ie, ≥3 APC clinic visits, ≥3 CHW home visits, and Chronic Disease Self-Management Program workshops), and additional telephone visits, protocol-driven risk factor management, culturally and linguistically tailored education materials, and self-management tools. Participants randomized to the control group received usual care, which varied by site but frequently included a free BP monitor, self-management tools, and linguistically tailored information materials. Main Outcomes and Measures The primary outcome was change in systolic BP at 12 months. Secondary outcomes were non–high density lipoprotein cholesterol, hemoglobin A1c, and C-reactive protein (CRP) levels, body mass index, antithrombotic adherence, physical activity level, diet, and smoking status at 12 months. Potential mediators assessed included access to care, health and stroke literacy, self-efficacy, perceptions of care, and BP monitor use. Results Among 487 participants included, the mean (SD) age was 57.1 (8.9) years; 317 (65.1%) were men, and 347 participants (71.3%) were Hispanic, 87 participants (18.3%) were Black, and 30 participants (6.3%) were Asian. A total of 246 participants were randomized to usual care, and 241 participants were randomized to the intervention. Mean (SD) systolic BP improved from 143 (17) mm Hg at baseline to 133 (20) mm Hg at 12 months in the intervention group and from 146 (19) mm Hg at baseline to 137 (22) mm Hg at 12 months in the usual care group, with no significant differences in the change between groups. Compared with the control group, participants in the intervention group had greater improvements in self-reported salt intake (difference, 15.4 [95% CI, 4.4 to 26.0]; P = .004) and serum CRP level (difference in log CRP, −0.4 [95% CI, −0.7 to −0.1] mg/dL; P = .003); there were no differences in other secondary outcomes. Although 216 participants (89.6%) in the intervention group received some of the 3 core components, only 35 participants (14.5%) received the intended full dose. Conclusions and Relevance This randomized clinical trial of a complex multilevel, multimodal intervention did not find vascular risk factor improvements beyond that of usual care; however, further studies may consider testing the SUCCEED intervention with modifications to enhance implementation and participant engagement. Trial Registration ClinicalTrials.gov Identifier: NCT01763203

Purpose of ReviewMunchausen syndrome by tissue plasminogen activator (tPA) is a phenomenon we describe as patients exhibiting factitious symptoms to assume the role of the sick patient, desiring and received tPA, with no alternative diagnosis or secondary gain to better account for their presentation. To illustrate this phenomenon and its magnitude, we present a series of cases of Munchausen syndrome by tPA, prevalence in our stroke center, and highlight one illustrative case.Recent FindingsOf 335 cases with tPA administration over 29 months, 10 were confirmed as Munchausen syndrome by tPA, reflecting a 3.0% prevalence in our stroke center.SummaryMunchausen syndrome by tPA is an underappreciated phenomenon encountered in evaluating patients with acute stroke symptoms. Administering tPA in Munchausen syndrome poses an ethical dilemma because standard of care favors rapid tPA administration, but administration can cause harm, burdens the healthcare system, and does not treat the patient's Munchausen syndrome.

Background and Purpose: Self-management programs may improve quality of life and self-efficacy for stroke survivors, but participation is low. In a randomized controlled trial of a complex, multidisciplinary, team-based secondary stroke prevention intervention, we offered participants Chronic Disease Self-Management Program (CDSMP) workshops in addition to clinic visits and home visits. To enhance participation, workshops were facilitated by community health workers who were culturally and linguistically concordant with most participants and scheduled CDSMP sessions at convenient venues and times. Over time, we implemented additional strategies such as free transportation and financial incentives. In this study, we aimed to determine factors associated with CDSMP participation and attendance. Methods: From 2014 to 2018, 18 CDSMP workshop series were offered to 241 English and Spanish-speaking individuals (age ≥40 years) with recent stroke or transient ischemic attack. Zero-inflated Poisson regression was used to identify factors associated with participation and attendance (ie, number of sessions attended) in CDSMP. Missing values were imputed using multiple imputation methods. Results: Nearly one-third (29%) of intervention subjects participated in CDSMP. Moderate disability and more clinic/home visits were associated with participation. Participants with higher numbers of clinic and home visits (incidence rate ratio [IRR], 1.06 [95% CI, 1.01–1.12]), severe (IRR, 2.34 [95% CI, 1.65–3.31]), and moderately severe disability (IRR, 1.55 [95% CI, 1.07–2.23]), and who enrolled later in the study (IRR, 1.12 [95% CI, 1.08–1.16]) attended more sessions. Individuals with higher chaos scores attended fewer sessions (IRR, 0.97 [95% CI, 0.95–0.99]). Conclusions: Less than one-third of subjects enrolled in the SUCCEED (Secondary Stroke Prevention by Uniting Community and Chronic Care Model Teams Early to End Disparities) intervention participated in CDSMP; however, participation improved as transportation and financial barriers were addressed. Strategies to address social determinants of health contributing to chaos and engage individuals in healthcare may facilitate attendance. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01763203.

Background: Agonism of protease-activated receptor 1 (PAR1) potently protects neurons and vasculature in the central nervous system during stroke. We evaluated the effects of 3K3A-APC, a recombinant variant of activated protein C active at PAR1, in acute ischemic stroke patients during conventional recanalization with thrombolysis or thrombectomy or both. We hypothesized that 3K3A-APC would reduce post-treatment hemorrhage and symptomatic neurologic deterioration. Methods: Using the NeuroNEXT trial NN104 (RHAPSODY) database, susceptibility weighted and gradient echo images were graded for intracerebral hemorrhage size according to radiographic criteria described in ECASS (Hemorrhagic infarction type 1 and 2 and parenchymal hematoma type 1 and 2) at four time points (0, 7, 30, and 90 days after treatment). Of 110 participants enrolled, 101 had appropriate imaging for analysis. Images were evaluated and graded by two blinded, independent raters with an expert providing consensus reads. Utilizing NIHSS following drug treatment, neurological worsening was defined as an increase in NIHSS ≥ 4 points. We compared placebo versus drug administration using multi-variate regression. Results: Of 101 participants evaluated, those receiving placebo (n=41) were significantly more likely to have hemorrhage at any time compared with those receiving any amount of drug (n=60) (p = 0.04; CI: 1.080 - 7.544; OR = 2.73). Age was found to be the only significant variable leading independently to increased neurological worsening (p = 0.038; CI: 1.015-1.193; OR = 1.086). Conclusion: The neuroprotectant 3K3A-APC showed significant reduction in hemorrhagic transformation when co-administered with conventional recanalization therapy. Further studies are underway for determining the effect of 3K3A-APC on functional outcome.

Background: Minority and socioeconomically disadvantaged individuals are underrepresented in secondary stroke prevention trials. Little is known about factors associated with study retention in these populations. Objective: To evaluate the impact of sociodemographic characteristics on retention in the Secondary stroke prevention by Uniting Community and Chronic care model teams Early to End Disparities (SUCCEED) trial. Methods: 487 participants ≥40 years with stroke/TIA were recruited from 4 safety-net hospitals and 1 stroke center serving low income zip codes. Strategies for boosting retention included: having bilingual research assistants from similar cultures establish rapport and follow participants; culturally and linguistically tailoring materials; arranging visits around participants’ schedules; offering transportation, and conducting assessments in the home and community. We compared sociodemographic characteristics among those retained at 12 months (n=412) vs. those not retained (n=75) using t-test, Chi Square, and Fisher exact tests. Independent factors associated with retention were determined using logistic regression. Results: Average age was 57 years, 18% were black, 71% were Hispanic, 58% were Spanish-speaking, and 72% were born outside the US. 12-month retention was 85%. On bivariate analysis, factors associated with retention were: Spanish-speaking, Hispanic ethnicity, younger age, born outside the US, and married status (all p Discussion: In this secondary prevention trial of stroke survivors from predominantly minority backgrounds, younger age, marriage, and insurance were associated with retention, suggesting that addressing barriers in the elderly, and those without insurance or spousal support may be beneficial. Financial constraints were associated with retention suggesting that study participation appealed to more socioeconomically vulnerable individuals.

Background: Approximately 25 million people in the US are Limited English Proficient (LEP). LEP individuals are more likely to feel dissatisfied with the quality of healthcare when compared to the English proficient, but little is known about LEP stroke survivors. Objective: To evaluate differences in stroke literacy, self-efficacy, and perceptions of healthcare delivery in English and Spanish-speaking individuals enrolled in the Secondary stroke prevention by Uniting Community and Chronic care model teams Early to End Disparities (SUCCEED) trial. Methods: SUCCEED participants were given the option of receiving the intervention in English or Spanish. Baseline differences in stroke literacy (Schneider et al), self-efficacy (General Self-Efficacy Scale), and perceptions of care (Patient Assessment of Chronic Illness Care and Consumer Assessment of Healthcare Providers and Systems) were compared using T-test, Chi Square, and Fisher Exact in individuals who chose Spanish vs. English. Results: Of 487 participants, 207 preferred English and 280 chose Spanish. Despite feeling more worried about having a stroke (77 % vs. 67%), and feeling at risk of having a stroke (63% vs. 45%), Spanish-speakers were less likely to identify 3 stroke risk factors (19% vs. 33%, all p Conclusion: Among stroke survivors, Spanish-speakers were more likely to have low stroke literacy, low self-efficacy, and a negative perception of healthcare delivery despite feeling that healthcare was accessible. Recognizing language barriers as a contributor to healthcare disparities, and tailoring interventions to address these barriers are crucial.

Introduction: Intracranial atherosclerotic disease (ICAD) correlates highly with transient ischemic attack (TIA) and acute ischemic stroke (AIS). Magnetic Resonance (MR) vessel wall imaging (VWI) is an emerging non-invasive imaging modality for directly assessing ICAD lesions. Methods: We retrospectively analyzed MR-VWI from 42 TIA patients and 45 AIS patients with ICAD. All patients fulfilled the following criteria: (1) stenosis >30% of a middle cerebral artery (MCA), (2) symptoms contralateral to stenotic MCA, (3) no coexisting stenosis at other major vessels; (4) lack of compelling evidence to other etiologies of stroke/TIA. Vascular lesions were analyzed with MR-VWI with respect to the stenosis degree, vessel wall irregularity, plaque burden (PB), remodeling index (RI), plaque-wall contrast ratio (CR) and plaque enhancement grade (EG). Results: EG (OR 3.88, 95%CI 1.42-10.57, P=0.006) was a risk factor for AIS while PB (OR 0.65, 95%CI 0.27-1.54, P=0.008) was a risk factor for TIA. In patients with 30-70% degree stenosis, CR (OR 5.38, 95%CI 1.39-20.75, P=0.008) was a risk factor for stroke, while PB (OR 0.4, 95%CI 0.1-1.65, P=0.006) remained a risk factor for TIA. Conclusions: In our study, PB appeared as a risk factor for TIA but not for AIS. This suggests that unstable plaque accounting for AIS may have a wide range of PB. We further found that CR and EG are more associated with AIS than TIA. Lesions with high CR and strong enhancement may be more prone to producing the permanent ischemic injury. Further study is needed to elucidate the role of MR-VWI in differential diagnosis and management of TIA and AIS.

Takayasu’s arteritis is a chronic idiopathic inflammatory large vessel vasculitis affecting mostly young adults. The disease process predominantly involves the aorta and its main branches such as the carotid and subclavian arteries. Vessel wall inflammation leads to stenosis, occlusion, or aneurysmal dilation of involved arteries and subsequent end-organ damage. Clinical presentations vary and range from nonspecific constitutional symptoms to symptoms associated with vascular injury, such as pulselessness, limb claudication, renovascular hypertension, angina, carotidynia, and strokes. In addition to comprehensive clinical assessment, imaging techniques, such as ultrasound, Magnetic Resonance Angiography (MRA), Computed Tomography Angiography (CTA) and Positron Emission Tomography (PET) play a critical role in establishing diagnosis and monitoring disease progression and response to treatment. Therapeutic strategies consist of medical therapy focused on immunosuppressive therapy and more recently, biological-targeted therapy. Endovascular and surgical interventions will also be discussed.

Background: Intracranial atherosclerotic disease (ICAD) is one of the most challenging stroke etiologies, with frequent recurrences despite optimized medical management. Encephaloduroarteriosynangiosis (EDAS) is an indirect revascularization method that produces collaterals from the extracranial circulation into cerebral hypoperfused areas. We present the results of a phase-II trial of EDAS in patients with ICAD failing medical management. Methods: ERSIAS was a prospective objective performance criterion (OPC) trial of EDAS plus intensive medical management (IMM) in patients with symptomatic ICAD despite optimized medical management, and poor angiographic collaterals. The primary endpoint was any stroke or death within 30 days postsurgery or stroke in the territory of the qualifying artery beyond 30 days. The primary analysis compared event rates through one year with the OPC of 10·1%, based on a 10% reduction from the 20·1% rate in the IMM arm of SAMMPRIS trial. The event rates through two years were compared with propensity-score-matched (PSM) medically treated patients from the SAMPPRIS and COSS trials. Secondary endpoints included functional neurological outcome and angiographic neovascularization. Findings: Fifty-two patients underwent EDAS-plus-IMM. The median age was 52 years (IQR=38·3-65·8), and 32 were females (61·5%). The primary endpoint rate at one year was 9·6%, lower than the OPC of 10·1% (p=0·07), meeting the p

Background One of the potentially important applications of three-dimensional (3D) intracranial vessel wall (IVW) cardiovascular magnetic resonance (CMR) is to monitor disease progression and regression via quantitative measurement of IVW morphology during medical management or drug development. However, a prerequisite for this application is to validate that IVW morphologic measurements based on the modality are reliable. In this study we performed comprehensive reliability analysis for the recently proposed whole-brain IVW CMR technique. Methods Thirty-four healthy subjects and 10 patients with known intracranial atherosclerotic disease underwent repeat whole-brain IVW CMR scans. In 19 of the 34 subjects, two-dimensional (2D) turbo spin-echo (TSE) scan was performed to serve as a reference for the assessment of vessel dimensions. Lumen and wall volume, normalized wall index, mean and maximum wall thickness were measured in both 3D and 2D IVW CMR images. Scan-rescan, intra-observer, and inter-observer reproducibility of 3D IVW CMR in the quantification of IVW or plaque dimensions were respectively assessed in volunteers and patients as well as for different healthy subjectsub-groups (i.e. 0.75). In addition, all ICCs of patients were equal to or higher than that of healthy subjects except maximum wall thickness. In volunteers, all ICCs of the age group of ≥50 years were equal to or higher than that of the age group of

Intracranial atherosclerotic disease (ICAD) is a common cause of stroke with high rates of ischemic recurrence. We aimed to investigate the role of circulating exosomal microRNAs (e-miRNAs) in recurrent ischemic events in ICAD. Consecutive patients with severe ICAD undergoing intensive medical management (IMM) were prospectively enrolled. Those with recurrent ischemic events despite IMM during 6-month follow up were algorithmically matched to IMM responders. Baseline blood e-miRNA expression levels of the matched patients were measured using next generation sequencing. A total of 122 e-miRNAs were isolated from blood samples of 10 non-responders and 11 responders. Thirteen e-miRNAs predicted IMM failure with 90% sensitivity and 100% specificity. Ingenuity pathway analysis (IPA) determined 10 of the 13 e-miRNAs were significantly associated with angiogenesis-related biological functions (p 0.025) and angiogenic factors that have been associated with recurrent ischemic events in ICAD. These e-miRNAs included miR-122-5p, miR-192-5p, miR-27b-3p, miR-16-5p, miR-486-5p, miR-30c-5p, miR-10b-5p, miR-10a-5p, miR-101-3p, and miR-24-3p. As predicted by IPA, the specific expression profiles of these 10 e-miRNAs in non-responders had a net result of inhibition of the angiogenesis-related functions and up expression of the antiangiogenic factors. This study revealed distinct expression profiles of circulating e-miRNAs in refractory ICAD, suggesting an antiangiogenic mechanism underlying IMM failure.

Purpose To propose and evaluate a parameter tune-up solution to expedite a three-dimensional (3D) variable-flip-angle turbo spin-echo (TSE) sequence for whole-brain intracranial vessel wall (IVW) imaging. Materials and Methods Elliptical k-space sampling and prolonged echo train length (ETL), were used to expedite a 3D variable-flip-angle TSE-based sequence. To compensate for the potential loss in vessel wall signal, optimal combination of prescribed T2 and ETL was experimentally investigated on 22 healthy volunteers at 3 Tesla. The optimized protocol (7–8 min) was then compared with a previous protocol (reference protocol, 11–12 min) in terms of signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), vessel wall sharpness, and wall delineation quality on a 4-point scale (0:poor; 3:excellent) in 10 healthy volunteers. A pilot study of five patients was performed and lesion delineation score was used to demonstrate the diagnostic quality. Results A protocol with ETL = 52 and prescribed T2 = 170 ms was deemed an optimized one, which, compared with the reference protocol, provided significantly improved wall SNR (12.0 ± 1.3 versus 10.0 ± 1.1; P = 0.002), wall–lumen CNR (9.7 ± 1.2 versus 8.0 ± 0.9; P = 0.002), wall–CSF CNR (2.8 ± 1.0 versus 1.7 ± 1.0; P = 0.026), similar vessel wall sharpness at both inner (1.59 ± 0.18 versus 1.58 ± 0.14, P = 0.87) and outer (1.71 ± 0.25 versus 1.83 ± 0.30; P = 0.18) boundaries, and comparable vessel wall delineation score for individual segments (1.95–3; P > 0.06). In all patients, atherosclerotic plaques (10) or wall dissection (5) were identified with a delineation score of 3 or 2. Conclusion A parameter tune-up solution can accelerate 3D variable-flip-angle TSE acquisitions, particularly allowed for expedited whole-brain IVW imaging with preserved wall delineation quality. Level of Evidence: 2. J. Magn. Reson. Imaging 2017.

Tissue plasminogen activator (tPA) is currently a standard of care for acute stroke patients. One of the necessary criteria in determining eligibility for tPA is the last known well (LKW) time. The LKW time is unfortunately often difficult to obtain accurately if no witness is available, thus posing as an obstacle for acute recanalization therapy. We present the case of a patient who arrived unresponsive with an unwitnessed onset of symptoms concerning for an acute stroke. An LKW time was able to be successfully established by using her fingerprint to unlock her phone and discover a coherent text sent a few hours prior. Patient was able to receive intravenous (IV) tPA and demonstrated remarkable recovery. The use of fingerprint ID to unlock the patient’s phone raises the concern of breach of privacy and whether involuntary smartphone searches apply to the emergency code of conduct outlined by the FDA. Smartphone applications, such as Apple iOS “Medical ID” argues for maximal utilization of smartphone technology for emergent medical conditions. Utilization of smartphone technology can potentially serve a potential solution, but the question remains as to whether this practice would be deemed to be ethically appropriate under the policy of implied informed consent under emergent conditions. J Med Cases. 2020;11(2):44-45 doi: https://doi.org/10.14740/jmc3431

Background and Purpose— The WEAVE trial (Wingspan Stent System Post Market Surveillance) is a postmarket surveillance trial mandated by the Food and Drug Administration to assess the periprocedural safety of the Wingspan Stent system in the treatment of symptomatic intracranial atherosclerotic disease. Methods— A total of 152 consecutive patients who met the Food and Drug Administration on-label usage criteria were enrolled at 24 hospitals and underwent angioplasty and stenting with the Wingspan stent. On-label criteria included age 22 to 80 years, symptomatic intracranial atherosclerotic stenosis of 70% to 99%, baseline modified Rankin Scale score ≤3, ≥2 strokes in the vascular territory of the stenotic lesion with at least 1 stroke while on medical therapy, and stenting of the lesion ≥8 days after the last stroke. The primary analysis assessed the periprocedural stroke, bleed, and death rate within 72 hours of the procedure with adjudication by a core study Stroke Neurologist. Results— The trial was stopped early after interim analysis of 152 consecutive patients demonstrated a lower than expected 2.6% (4/152 patients) periprocedural stroke, bleed, and death rate. This was lower than the 4% periprocedural primary event safety benchmark set for the interim analysis in the study. A total of 97.4% (148/152) patients were event-free at 72 hours, 1.3% (2/152) had nonfatal strokes, and 1.3% (2/152) of patients died. Conclusions— With experienced interventionalists, and proper patient selection following the on-label usage guidelines, the use of the Wingspan stent for intracranial atherosclerotic disease demonstrated a low periprocedural complication rate and excellent safety profile. This is the largest on-label, multicenter, prospective trial of the Wingspan stent system to date with the lowest reported complication rate. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT02034058.

Background: Minority, disadvantaged populations are often underrepresented in secondary stroke prevention trials despite known disparities in risk factor control. When they do enroll, retention is poor due to competing needs, transiency, unstable housing, transportation barriers, and inconsistent telephone access. Methods: We recruited 487 English- or Spanish-speaking adults (age >40 yrs) with a recent TIA or ischemic/hemorrhagic stroke, and systolic BP ≥130 mm Hg or diagnosed hypertension and SBP≥120mm Hg, from 4 Los Angeles County-Department of Health Services hospitals and 1 stroke center serving low income zip codes. We used recruitment and retention strategies from a prior trial; leadership and staff met regularly to track progress and design and implement new strategies. Meeting notes were reviewed to compile approaches . Results: Average age was 57.1 years; race/ethnicity was 71.4% Hispanic, 17.6% black, 6.4% Asian; 72.5% were born outside the US; 62.6% had not graduated high school; 40% rarely spoke English at home. Follow-up data collection was 440/487 (90%) at 3 months, 382/487 (78%) at 8 months, and 394/475 (83%) of eligibles at 12 months. Prior recruitment strategies used were bilingual research assistants (RAs) from similar cultural backgrounds, inpatient clinical team introduction of potential enrollees to RAs, embedding RAs on the inpatient unit, piloting and tailoring recruitment scripts prior to study initiation, and allowing potential participants to discuss the study with others prior to enrollment. Prior retention strategies used were obtaining ≥3 contact numbers at enrollment and reviewing medical records for upcoming appointments. New retention strategies developed and applied were offering in-home assessments, providing transportation, offering weekend/evening visits, using phone, mail, and registered mail to contact participants, routinely using the same RA for a given participant, and reminding patients of prior interactions with RAs/visits. Conclusion: To maximize retention and recruitment, the combined approach of beginning with a broad set of previously effective strategies, and tracking and developing new ones over the course of the trial was effective. Trial Registry Trial Number: NCT01763203

Introduction: Recent patent foramen ovale (PFO) closure trials have demonstrated efficacy in secondary stroke prevention. Transcranial Doppler (TCD) can reliably detect the presence of PFO, with sensitivity comparable to echocardiography. We sought to compare the sensitivity of TCD in detecting right to left shunt (RLS) using transesophageal echocardiogram (TEE) criteria as described in the CLOSE and REDUCE trials. Methods: We retrospectively reviewed all TCD studies at our institution who also had TEE studies. We excluded patients who had their PFO closed prior to one of these studies being performed. We classified the size of the PFO based on both REDUCE and CLOSE criteria (large was defined as greater than 25 microbubbles and greater than 30 microbubbles, respectively) and compared to the size based on the Spencer grade. Results: A total of 525 TCD bubble studies were performed at our institution from May 2013 to June 2018, 220 of which also underwent TEE. Using TEE as the gold standard, TCD detected 97.61% (41/42) of any moderate-large RLS and 100% (10/10) of any large RLS. The single patient who had a moderate RLS on TEE, but not TCD had a poor Valsalva during the TCD study. TCD detected 33 patients with RLS not detected on TEE [33% (33/100)], 33.3% of which were considered significant (Spencer grades 3-5). Conclusion: TCD is comparable to TEE in detecting moderate-to-large RLS based on REDUCE/CLOSE criteria. TCD detected an appreciable amount of RLS (a third of which were Spencer grades 3-5) not detected by TEE. Further study is needed to clarify the role of PFO closure in patients with significant RLS on TCD, but no RLS on TEE. TCD is a good alternative screening tool for RLS as compared with TEE methods from recent positive trials.

Purpose Although three-dimensional (3D) turbo spin echo (TSE) with variable flip angles has proven to be useful for intracranial vessel wall imaging, it is associated with inadequate suppression of cerebrospinal fluid (CSF) signals and limited spatial coverage at 3 Tesla (T). This work aimed to modify the sequence and develop a protocol to achieve whole-brain, CSF-attenuated T1-weighted vessel wall imaging. Methods Nonselective excitation and a flip-down radiofrequency pulse module were incorporated into a commercial 3D TSE sequence. A protocol based on the sequence was designed to achieve T1-weighted vessel wall imaging with whole-brain spatial coverage, enhanced CSF-signal suppression, and isotropic 0.5-mm resolution. Human volunteer and pilot patient studies were performed to qualitatively and quantitatively demonstrate the advantages of the sequence. Results Compared with the original sequence, the modified sequence significantly improved the T1-weighted image contrast score (2.07 ± 0.19 versus 3.00 ± 0.00, P = 0.011), vessel wall-to-CSF contrast ratio (0.14 ± 0.16 versus 0.52 ± 0.30, P = 0.007) and contrast-to-noise ratio (1.69 ± 2.18 versus 4.26 ± 2.30, P = 0.022). Significant improvement in vessel wall outer boundary sharpness was observed in several major arterial segments. Conclusions The new 3D TSE sequence allows for high-quality T1-weighted intracranial vessel wall imaging at 3 T. It may potentially aid in depicting small arteries and revealing T1-mediated high-signal wall abnormalities. Magn Reson Med 77:1142–1150, 2017. © 2016 International Society for Magnetic Resonance in Medicine

BACKGROUND: Vascular endothelial growth factor-A(165) (VEGF-A(165)) has been identified as a combination of two alternative splice variants: proangiogenic VEGF-A(165)a and antiangiogenic VEGF-A(165)b. Intracranial atherosclerotic disease (ICAD) and moyamoya disease (MMD) are two main types of intracranial arterial steno-occlusive disorders (ICASD) with distinct capacities for collateral formation. Recent studies indicate that VEGF-A(165) regulates collateral growth in ischemia. Therefore, we investigated if there is a distinctive composition of VEGF-A(165) isoforms in ICAD and MMD. METHODS: Sixty-six ICAD patients, six MMD patients, and five controls were enrolled in this prospective study. ICAD and MMD patients received intensive medical management upon enrollment. Surgery was offered to 9 ICAD patients who had recurrent ischemic events, 6 MMD patients, and 5 surgical controls without ICAD. VEGF-A(165)a and VEGF-A(165)b plasma levels were measured at baseline, within one week after patients having surgery, and at one, three, and six months after treatment. RESULTS: A significantly higher baseline VEGF-A(165)a/b ratio was observed in MMD compared to ICAD (p=0.016). The VEGF-A(165)a/b ratio increased significantly and rapidly after surgical treatment in ICAD (p=0.026) more so than in MMD and surgical controls. In patients with ICAD receiving intensive medical management, there was also an elevation of the VEGF-A(165)a/b ratio, but at a slower rate, reaching the peak at three months after initiation of treatment (baseline vs. three months VEGF-A(165)a/b ratio, p=0.028). CONCLUSIONS: Our study shows an increased VEGF-A(165)a/b ratio in MMD compared to ICAD, and suggests that both intensive medical management and surgical revascularization elevate the VEGF-A(165)a/b ratio in ICAD patients.

Objective Most acute ischemic stroke (AIS) patients with unwitnessed symptom onset are ineligible for intravenous thrombolysis due to timing alone. Lesion evolution on fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) correlates with stroke duration, and quantitative mismatch of diffusion-weighted MRI with FLAIR (qDFM) might indicate stroke duration within guideline-recommended thrombolysis. We tested whether intravenous thrombolysis ≤4.5 hours from the time of symptom discovery is safe in patients with qDFM in an open-label, phase 2a, prospective study (NCT01282242). Methods Patients aged 18 to 85 years with AIS of unwitnessed onset at 4.5 to 24 hours since they were last known to be well, treatable within 4.5 hours of symptom discovery with intravenous alteplase (0.9mg/kg), and presenting with qDFM were screened across 14 hospitals. The primary outcome was the risk of symptomatic intracranial hemorrhage (sICH) with preplanned stopping rules. Secondary outcomes included symptomatic brain edema risk, and functional outcomes of 90-day modified Rankin Scale (mRS). Results Eighty subjects were enrolled between January 31, 2011 and October 4, 2015 and treated with alteplase at median 11.2 hours (IQR = 9.5-13.3) from when they were last known to be well. There was 1 sICH (1.3%) and 3 cases of symptomatic edema (3.8%). At 90 days, 39% of subjects achieved mRS = 0-1, as did 48% of subjects who had vessel imaging and were without large vessel occlusions. Interpretation Intravenous thrombolysis within 4.5 hours of symptom discovery in patients with unwitnessed stroke selected by qDFM, who are beyond the recommended time windows, is safe. A randomized trial testing efficacy using qDFM appears feasible and is warranted in patients without large vessel occlusions. Ann Neurol 2018;83:980-993.