Publications by authors named "Shlee S Song"

22 Publications

  • Page 1 of 1

Ischemic Stroke in the Young.

Clin Appl Thromb Hemost 2021 Jan-Dec;27:10760296211002274

Department of Neurology, Comprehensive Stroke Center Program, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/10760296211002274DOI Listing
April 2021

Effect of a Coordinated Community and Chronic Care Model Team Intervention vs Usual Care on Systolic Blood Pressure in Patients With Stroke or Transient Ischemic Attack: The SUCCEED Randomized Clinical Trial.

JAMA Netw Open 2021 02 1;4(2):e2036227. Epub 2021 Feb 1.

Rancho Los Amigos National Rehabilitation Center, Downey, California.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamanetworkopen.2020.36227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885035PMC
February 2021

Plaque Morphologic Quantification Reliability of 3D Whole-Brain Vessel Wall Imaging in Patients With Intracranial Atherosclerotic Disease: A Comparison With Conventional 3D Targeted Vessel Wall Imaging.

J Magn Reson Imaging 2021 Feb 15. Epub 2021 Feb 15.

Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.

Background: Three-dimensional (3D) whole-brain vessel wall imaging (VWI) has demonstrated exquisite image quality for delineating intracranial atherosclerotic disease (ICAD) and reliability for quantifying normal vessel dimensions. However, its reliability in quantifying plaque morphology remains unknown.

Purpose: To evaluate the plaque morphologic quantification reliability of 3D whole-brain VWI in patients via comparison with 3D targeted VWI and 2D turbo spin-echo (TSE).

Study Type: Prospective.

Population: Thirty-three patients with symptomatic ICAD.

Field Strength/sequence: A 3D and 2D TSE acquired at 3.0 T.

Assessment: Each participant underwent two VWI sessions with an interval of 7-10 days. Three readers identified in consensus all the plaques on both whole-brain and targeted 3D VWI. Their lumen and vessel wall area and volume, plaque burden, percent stenosis, and vessel wall remodeling were measured for by two independent readers. At each culprit plaque determined by a radiologist, the lumen and vessel wall area, plaque burden, plaque-to-wall contrast ratio (CR), and plaque enhancement ratio (ER) were measured for 2D and 3D VWI methods.

Statistical Tests: Intra-class correlation coefficient (ICC) was used to evaluate for 3D VWI's interobserver/intraobserver agreement, interscan repeatability, and agreement with 2D TSE in each plaque morphologic measurements. Paired t test was performed for detecting the differences in plaque-to-wall CR and plaque ER between the two 3D methods.

Results: Eighty-four plaques were detected by both 3D VWI methods. Whole-brain VWI provided excellent interobserver/intraobserver agreement (ICCs: 0.79-0.99/0.95-0.99), interscan repeatability (ICCs: 0.85-0.99), agreement with 2D TSE (ICC: 0.80-0.94) in all morphologic measurements. ICCs of whole-brain VWI (0.79-0.99) were higher or equal to those of targeted VWI (0.76-0.99). The plaque-to-wall CR and plaque ER were significantly higher on whole-brain VWI than on targeted VWI.

Data Conclusion: The 3D whole-brain VWI provides excellent interobserver/intraobserver agreement, interscan repeatability, and agreement with 2D TSE in plaque morphologic quantification of ICAD and outperforms 3D targeted VWI.

Level Of Evidence: 2 TECHNICAL EFFICACY STAGE: 2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmri.27550DOI Listing
February 2021

Acute ischemic stroke versus transient ischemic attack: Differential plaque morphological features in symptomatic intracranial atherosclerotic lesions.

Atherosclerosis 2021 02 11;319:72-78. Epub 2021 Jan 11.

Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd., PACT 400, Los Angeles, CA, USA; Department of Radiology, University of Southern California, Los Angeles, CA, USA; Department of Radiation Oncology, University of Southern California, Los Angeles, CA, USA. Electronic address:

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.atherosclerosis.2021.01.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880900PMC
February 2021

Magnetic Resonance Vessel Wall Imaging in Central Nervous System Vasculitides: A Case Series.

Neurologist 2020 Nov;25(6):174-177

Departments of Neurology.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/NRL.0000000000000298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668232PMC
November 2020

Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data.

Lancet 2020 11 8;396(10262):1574-1584. Epub 2020 Nov 8.

Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany.

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=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 [<1%], 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(20)32163-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734592PMC
November 2020

Training in Neurology: Adoption of resident teleneurology training in the wake of COVID-19: Telemedicine crash course.

Neurology 2020 09 17;95(9):404-407. Epub 2020 Jun 17.

From the Department of Neurology (A.M.Z., A.L.J.-C.), Institute of Stroke and Cerebrovascular Disease, University of Texas Health Science Center, Houston; Department of Neurology (L.S.C., J.J.M.), University of Utah, Salt Lake City; and Department of Neurology (S.S.S.), Cedars-Sinai Medical Center, Los Angeles, CA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000010029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538229PMC
September 2020

Magnetic resonance multitasking for multidimensional assessment of cardiovascular system: Development and feasibility study on the thoracic aorta.

Magn Reson Med 2020 11 16;84(5):2376-2388. Epub 2020 Apr 16.

Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, California.

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 T -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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mrm.28275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875090PMC
November 2020

Assessing Cerebrovascular Hemodynamics Using Transcranial Doppler in Patients with Mechanical Circulatory Support Devices.

J Neuroimaging 2020 05 10;30(3):297-302. Epub 2020 Feb 10.

Department of Neurology and Comprehensive Stroke Center, Cedars-Sinai Medical Center, Los Angeles, CA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jon.12694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7321834PMC
May 2020

Differential expression of circulating exosomal microRNAs in refractory intracranial atherosclerosis associated with antiangiogenesis.

Sci Rep 2019 12 19;9(1):19429. Epub 2019 Dec 19.

Department of Neurosurgery, Neurovascular Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-54542-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6923371PMC
December 2019

WEAVE Trial: Final Results in 152 On-Label Patients.

Stroke 2019 04;50(4):889-894

Department of Neurology, University of California - Irvine Medical Center (W.Y.).

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.118.023996DOI Listing
April 2019

Differential Expression of Vascular Endothelial Growth Factor-A Isoforms Between Intracranial Atherosclerosis and Moyamoya Disease.

J Stroke Cerebrovasc Dis 2019 Feb 2;28(2):360-368. Epub 2018 Nov 2.

Department of Neurosurgery, Gonzalez Neurovascular Laboratory, Cedars-Sinai Medical Center, Los Angeles, California; Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, California. Electronic address:

Background: Vascular endothelial growth factor-A (VEGF-A) has been identified as a combination of 2 alternative splice variants: proangiogenic VEGF-Aa and antiangiogenic VEGF-Ab. 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-A regulates collateral growth in ischemia. Therefore, we investigated if there is a distinctive composition of VEGF-A 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-Aa and VEGF-Ab 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-Aa/b ratio was observed in MMD compared to ICAD (P = .016). The VEGF-Aa/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-Aa/b ratio, but at a slower rate, reaching the peak at 3 months after initiation of treatment (baseline versus 3 months VEGF-Aa/b ratio, P = .028).

Conclusions: Our study shows an increased VEGF-Aa/b ratio in MMD compared to ICAD, and suggests that both intensive medical management and surgical revascularization elevate the VEGF-Aa/b ratio in ICAD patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2018.10.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6786492PMC
February 2019

Differential Features of Culprit Intracranial Atherosclerotic Lesions: A Whole-Brain Vessel Wall Imaging Study in Patients With Acute Ischemic Stroke.

J Am Heart Assoc 2018 07 22;7(15). Epub 2018 Jul 22.

Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA

Background: Intracranial atherosclerotic disease tends to affect multiple arterial segments. Using whole-brain vessel wall imaging, we sought to study the differences in plaque features among various types of plaques in patients with a recent unilateral anterior circulation ischemic stroke.

Methods And Results: Sixty-one patients with unilateral anterior circulation ischemic stroke were referred to undergo whole-brain vessel wall imaging (before and after contrast) within 1 month of symptom onset for intracranial atherosclerotic disease evaluations. Each plaque was classified as a culprit, probably culprit, or nonculprit lesion, according to its likelihood of causing the stroke. The associations between plaque features (thickening pattern, plaque-wall contrast ratio, high signal on T1-weighted images, plaque contrast enhancement ratio, enhancement grade, and enhancement pattern) and culprit lesions were estimated using mixed multivariable logistic regression after adjustment for maximum wall thickness. In 52 patients without motion corruption in whole-brain vessel wall imaging, a total of 178 intracranial plaques in the anterior circulation were identified, including 52 culprit lesions (29.2%), 51 probably culprit lesions (28.7%), and 75 nonculprit lesions (42.1%). High signal on T1-weighted images (adjusted odds ratio, 9.1; 95% confidence interval, 1.9-44.1; =0.006), grade 2 (enhancement ratio of plaque ≥ enhancement ratio of pituitary) contrast enhancement (adjusted odds ratio, 17.4; 95% confidence interval, 1.8-164.9; =0.013), and type 2 (≥50% cross-sectional wall involvement) enhancement pattern (adjusted odds ratio, 10.1; 95% confidence interval, 1.3-82.2; =0.030) were independently associated with culprit lesions.

Conclusions: High signal on T1-weighted images, grade 2 contrast enhancement, and type 2 enhancement pattern are associated with cerebrovascular ischemic events, which may provide valuable insights into risk stratification.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.118.009705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6201468PMC
July 2018

3D whole-brain vessel wall cardiovascular magnetic resonance imaging: a study on the reliability in the quantification of intracranial vessel dimensions.

J Cardiovasc Magn Reson 2018 06 14;20(1):39. Epub 2018 Jun 14.

Biomedical Imaging Research Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Blvd., PACT 400, Los Angeles, CA, 90048, USA.

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. < 50 and ≥ 50 years). The agreement in vessel wall and lumen measurements between the 3D technique and the 2D TSE method was also investigated. In addition, the sample size required for future longitudinal clinical studies was calculated.

Results: The intra-class correlation coefficient (ICC) and Bland-Altman plots indicated excellent reproducibility and inter-method agreement for all morphologic measurements (All ICCs > 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 < 50 years. Normalized wall index and mean and maximum wall thickness were significantly larger in the age group of ≥50 years. To detect 5% - 20% difference between placebo and treatment groups, normalized wall index requires the smallest sample size while lumen volume requires the highest sample size.

Conclusions: Whole-brain 3D IVW CMR is a reliable imaging method for the quantification of intracranial vessel dimensions and could potentially be useful for monitoring plaque progression and regression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12968-018-0453-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6000985PMC
June 2018

Intravenous thrombolysis in unwitnessed stroke onset: MR WITNESS trial results.

Ann Neurol 2018 05 27;83(5):980-993. Epub 2018 Apr 27.

Dell Medical School, University of Texas at Austin, Austin, TX.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ana.25235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6095471PMC
May 2018

Management of Factor Xa inhibitor-associated life-threatening major hemorrhage: A retrospective multi-center analysis.

Am J Emerg Med 2018 Mar 19;36(3):396-402. Epub 2017 Aug 19.

Navigant Consulting Inc., London, United Kingdom.

Background: Factor Xa (FXa) inhibitors, used for stroke prevention in atrial fibrillation and venous thromboembolism treatment and prevention, are the dominant non-Vitamin K oral anticoagulants on the market. While major bleeding may be less common with these agents compared to warfarin, it is always a risk, and little has been published on the most serious bleeding scenarios. This study describes a cohort of patients with FXa inhibitor-associated life-threatening bleeding events, their clinical characteristics, interventions and outcomes.

Methods: We performed a retrospective, 5-center review of FXa inhibitor-treated major bleeding patients. Investigators identified potential cases by cross-referencing ICD-9/10 codes for hemorrhage with medication lists. Investigators selected cases they deemed to require immediate reversal of coagulopathy, and reviewed charts for characteristics, reversal strategies and other interventions, and outcomes.

Results: A total of 56 charts met the inclusion criteria for the retrospective cohort, including 29 (52%) gastrointestinal bleeds (GIB), 19 (34%) intracranial hemorrhages (ICH) and 8 (14%) others. Twenty-four (43%) patients received various factor or plasma products, and the remainder received supportive care. Thirty-day mortality was 21% (n=12). Re-anticoagulation within 30-days occurred in 23 (41%) patients. Thromboembolic events (TEEs) occurred in 6 (11%) patients. No differences were observed in outcomes by treatment strategy.

Conclusions: This cohort of FXa inhibitor-associated major bleeding scenarios deemed appropriate for acute anticoagulant reversal illustrates the variable approaches in the absence of a specific reversal agent.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajem.2017.08.042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6049660PMC
March 2018

Pitfalls and Rewards for Implementing Ocular Motor Testing in Acute Vestibular Syndrome: A Pilot Project.

Neurologist 2017 Mar;22(2):44-47

Departments of *Neurology †Emergency Medicine ‡Biostatistics and Bioinformatics, Cedars-Sinai Medical Center, Los Angeles, CA §Departments of Neurology and Otolaryngology, The Johns Hopkins University School of Medicine, Baltimore, MD.

Objectives: Isolated acute vestibular syndrome (iAVS) presentations to the emergency department (ED) pose management challenges, given the concerns for posterior circulation strokes. False-negative brain imaging may erroneously reassure clinicians, whereas HINTS-plus examination outperforms imaging to screen for strokes in iAVS. We studied the feasibility of implementing HINTS-plus testing in the ED, aiming to reduce neuroimaging in patients with iAVS.

Methods: We launched an institutional Quality Improvement initiative, using DMAIC methodology. The outcome measures [proportion of iAVS subjects who had HINTS-plus examinations and underwent neuroimaging by computed tomography/magnetic resonance imaging (CT/MRI)] were compared before and after the established intervention. The intervention consisted of formal training for neurologists and emergency physicians on how to perform, document, and interpret HINTS-plus and implementation of novel iAVS management algorithm. Neuroimaging was not recommended if HINTS-plus suggested peripheral vestibular etiology. If a central process was suspected, brain MRI/MR angiogram was performed. Head CT was reserved only for thrombolytic time-window cases.

Results: In the first 2 months postimplementation, HINTS-plus testing performance by neurologists increased from 0% to 80% (P=0.007), and by ED providers from 0% to 9.09% (P=0.367). Head CT scans were reduced from 18.5% to 6.25%. Brain MRI use was reduced from 51.8% to 31.2%. About 60% of the iAVS subjects were discharged from the ED; none were readmitted or had another ED presentation in the ensuing 30 days.

Conclusions: Implementation of HINTS-plus evaluation in the ED is valuable and feasible for neurologists, but challenging for emergency physicians. Future studies should determine the "dose-response" curve of educational interventions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/NRL.0000000000000106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5334787PMC
March 2017

Whole-brain vessel wall MRI: A parameter tune-up solution to improve the scan efficiency of three-dimensional variable flip-angle turbo spin-echo.

J Magn Reson Imaging 2017 09 20;46(3):751-757. Epub 2017 Jan 20.

Biomedical Imaging Research Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA.

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 T 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 T  = 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. Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:751-757.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmri.25611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5519453PMC
September 2017

Advanced imaging in acute ischemic stroke.

Authors:
Shlee S Song

Semin Neurol 2013 Nov 6;33(5):436-40. Epub 2014 Feb 6.

Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, California.

Advances in stroke neuroimaging have evolved from excluding acute intracranial hemorrhage on computed tomography (CT) to now using perfusion studies (PWI) and magnetic resonance imaging (MRI) to possibly expand thrombolytic treatment to patients most likely to benefit from reperfusion therapy. Advanced imaging has also helped identify those at high risk for hemorrhage and poor outcome so appropriate treatment can occur with fewer complications. Identifying those who can benefit from endovascular recanalization using advanced neuroimaging techniques is particularly useful because endovascular treatment is often initiated much later than intravenous thrombolytic treatment due to logistical constraints. Using imaging markers of tissue injury may eventually lead to a paradigm shift from time-based treatment eligibility in acute stroke reperfusion treatment as the sensitivity and specificity to identify ischemic penumbra improves and correlation with clinical outcomes becomes clearer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0033-1364214DOI Listing
November 2013

Negative diffusion-weighted imaging after intravenous tissue-type plasminogen activator is rare and unlikely to indicate averted infarction.

Stroke 2013 Jun 9;44(6):1629-34. Epub 2013 Apr 9.

Section on Stroke Diagnostics and Therapeutics, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA.

Background And Purpose: Some patients treated with intravenous (IV) tissue-type plasminogen activator (tPA) have negative diffusion-weighted imaging (DWI) on follow-up imaging. Without a visible infarct, there may be uncertainty as to whether the patient was having a stroke that was averted by tPA or whether the symptoms had not been cerebrovascular in origin. We evaluated patients presenting with suspected acute stroke with a positive DWI lesion before IV tPA to determine the probability of finding a negative DWI up to 48 hours after treatment.

Methods: We included patients from the Lesion Evolution in Stroke and Ischemia On Neuroimaging (LESION) project who had acute MRI screening with a positive DWI lesion before IV tPA treatment and had follow-up MRI up to 48 hours later. Experienced readers interpreted all acute and follow-up MRIs looking for ischemic lesions on DWI.

Results: There were 231 patients who met study inclusion criteria, of which 225 patients (97.4%) had a persistent positive DWI corresponding to the acute stroke lesion on all follow-up imaging. Four patients (1.7%) had transient DWI lesion reversal with positive DWI on subsequent follow-up imaging. There were only 2 cases (0.9%) of complete DWI lesion reversal on all follow-up imaging.

Conclusions: Averted infarction after IV tPA is rare, occurring in 0.9% of patients with pretreatment positive DWI evidence of acute ischemia. For IV tPA-treated patients who have a negative DWI on follow-up imaging, a cause other than acute stroke should be explored.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.111.000486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3690771PMC
June 2013

Overview of therapeutic hypothermia.

Curr Treat Options Neurol 2012 Dec;14(6):541-8

Department of Neurology, Cedars-Sinai Medical Center, 8730 Alden Drive, Suite E-240, Los Angeles, CA, 90048, USA.

Opinion Statement: Therapeutic hypothermia has proven neuroprotective effects in global cerebral ischemia. Indications for hypothermia induction include cardiac arrest and neonatal asphyxia. The two general methods of induced hypothermia are either surface cooling or endovascular cooling. Hypothermia should be induced as early as possible to achieve maximum neuroprotection and edema blocking effect. Endovascular cooling has the benefit of shorter time to reach target temperature but catheter insertion requires expertise and training, which may be a barrier to widespread availability. The optimum method of cooling is yet to be determined but a multimodal approach is necessary to address three phases of cooling: induction, maintentance, and rewarm. Specifying core practitioners who are well-versed in established guidelines can help integrate the multidisciplinary team that is needed to successfully implement cooling protocols. Reducing shivering to make heat exchange more efficient with tighter temperature control enables quicker time to target temperature and avoids rewarming which can lead to inadvertent increase in intracranial pressure and cerebral edema. Promising applications but yet to be determined is whether hypothermia treatment can improve outcomes in acute ischemic stroke or traumatic brain injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11940-012-0201-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3519955PMC
December 2012

A pragmatic approach using magnetic resonance imaging to treat ischemic strokes of unknown onset time in a thrombolytic trial.

Stroke 2012 Sep 12;43(9):2331-5. Epub 2012 Jun 12.

Stroke Program, Department of Neurology, Cedars-Sinai Medical Center, 8730 Alden Drive, Thalians E-216, Los Angeles, CA, USA.

Background And Purpose: Toward the goal of designing a clinical trial using imaging parameters to treat stroke patients with unknown onset time, we investigated the timing of changes on MRI in patients with well-defined stroke onset.

Methods: Hypothesis-generating (n=85) and confirmatory (n=111) samples were scored by blinded readers for fluid-attenuated inversion recovery (FLAIR) hyperintensity in diffusion-positive regions. Reader-measured signal intensity ratio (SIR) of the lesion to contralateral tissue was compared with SIR measured by coregistration.

Results: Lesion conspicuity increased with time on FLAIR (P=0.006). Qualitative assessment of FLAIR-negative vs FLAIR hyperintensity (k=0.7091; 95% CI, 0.61-0.81) showed good interrater agreement. Subtle hyperintensity was less reliably categorized (k=0.59; 95% CI, 0.47-0.71). Reader-measured SIR <1.15 can identify patients within the treatable time window of 4.5 hours (positive predictive value=0.90). The SIR was greater for right hemisphere lesions (P=0.04) for a given reported time from stroke symptom onset.

Conclusions: The SIR on FLAIR provides a quantitative tool to identify early ischemic strokes. In developing SIR thresholds, right hemisphere lesions may confound the accurate estimate of stroke onset time. Image coregistration for thrombolytic trial enrollment is not necessary. A SIR <1.15 on FLAIR yields a practical estimate of stroke onset within 4.5 hours.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.111.630947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3464959PMC
September 2012