American Heart Association


Intensive LDL Cholesterol Lowering Improves Cardiovascular Outcomes in Patients With Recent TIA or Stroke

Ravinder-Jeet Singh, MBBS, DM

Amarenco P, Kim JS, Labreuche J, Charles H, Abtan J, Béjot Y, et al; Treat Stroke to Target Investigators. A Comparison of Two LDL Cholesterol Targets after Ischemic Stroke. N Engl J Med. 2020;382:9-19.

Several observational studies have investigated the effects of serum cholesterol levels (or its subfractions) on cardiovascular health and disease. These studies have shown that increased serum cholesterol is a strong risk factor for coronary artery disease, though association with stroke is less clear.(1-3) The inconsistent association between cholesterol and stroke could partly be explained by the difference in the effects of total cholesterol levels or its subfractions (especially LDL cholesterol) on the risk of ischemic vs hemorrhagic stroke, which are often combined in many epidemiologic studies. High total cholesterol is associated with higher risk of ischemic stroke, while low total cholesterol increases hemorrhagic stroke risk, and similar observations are noted with LDL cholesterol (LDL-C) levels as well.(2-6) Nonetheless, control of serum LDL-C levels constitutes standard recommendation for primary and secondary stroke prevention.(7)

Use of high-dose statins after a recent TIA or stroke was shown to reduce the incidence of stroke and other cardiovascular events in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial, despite a small increase in the incidence of hemorrhagic stroke.(8) Further, multiple clinical trials and their meta-analysis showed that more intensive LDL-C lowering is associated with greater reduction in cardiovascular events.(9) Whether intensive LDL-C lowering among patients with recent TIA/stroke lowers future stroke risk was not assessed in the previous trials. In the January issue of NEJM, Amarenco et al. reported the results of the Treat Stroke to Target (TST) trial, which compared two LDL-C targets after recent TIA and ischemic stroke.

Mechanical Thrombectomy in Vertebrobasilar Occlusion: Still Looking for Evidence

Elena Zapata-Arriaza, MD

Liu X, Dai Q, Ye R, Zi W, Liu Y, Wang H, et al. Endovascular treatment versus standard medical treatment for vertebrobasilar artery occlusion (BEST): an open-label, randomised controlled trial. Lancet Neurol. 2020;19:115-122.

Efficacy and safety of endovascular treatment (EVT) in anterior circulation strokes is clearly validated; however, such evidence is still lacking in vertebrobasilar occlusions. Liu et al. aimed to demonstrate safety and efficacy of EVT in posterior circulation strokes. To achieve this goal, the authors performed a multicenter, randomized, open-label trial in patients within 8 h of vertebrobasilar occlusion (basilar or V4 segment of vertebral artery). Patients were allocated to receive either EVT plus standard medical therapy or standard medical therapy alone. Given endovascular procedure, stent-retriever was the most employed technique, but thromboaspiration, intra-arterial thrombolysis, balloon angioplasty or stenting were also permitted. Primary outcome was mRS 0-3 at 90 days, assessed on an intention-to-treat basis. Primary safety outcome was mortality at 90 days. Secondary safety endpoints included symptomatic intracranial hemorrhage, device-related complications and other severe events rates. Each participating center had to have completed at least 5 mechanical thrombectomy procedures with stent retriever devices in the preceding year. The primary data analysis was done on the intention-to-treat population. In addition, secondary prespecified analyses were performed in the per-protocol population and in the as-treated population.

Author Interview: Dr. Houman Khosravani, MD, PhD, on “Protected Code Stroke: Hyperacute Stroke Management During the Coronavirus Disease 2019 (COVID-19) Pandemic”

Houman Khosravani
Houman Khosravani

A conversation with Houman Khosravani, MD, PhD, Assistant Professor, Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Canada. Twitter: @neuroccm

Interviewed by Victor J. Del Brutto, MD, Assistant Professor, Stroke Division, Department of Neurology, University of Miami Miller School of Medicine, Florida. Twitter: @vdelbrutto

They will be discussing the paper “Protected Code Stroke: Hyperacute Stroke Management During the Coronavirus Disease 2019 (COVID-19) Pandemic,” published in Stroke.

Dr. Del Brutto: First of all, I would like to thank you and your team for putting together these thoughtful recommendations on how to evaluate patients with suspected stroke during the Coronavirus Disease 2019 (COVID-19) pandemic. As a stroke neurologist, I share the global feeling of uncertainty that this pandemic has caused and look forward to modifying my institution practices in order to maximize patients’ outcomes, their safety, and the safety of the professionals involved in their care. In your article, you mention that stroke patients are at an increased risk of suboptimal outcomes during the COVID-19 pandemic. Could you please comment on the factors that may influence patient outcomes?

Dr. Khosravani: During the COVID-19 pandemic, patients are affected at several junctions in stroke care, including during the hyperacute phase. For example, paramedics responding to a stroke call, in some jurisdictions, will begin the screening process prior to arrival and then again on scene. When screening is positive, pre-notification to the hospital should occur, and this triggers a protected code stroke (PCS). Patients being brought directly to the ED will require additional screening. The necessary use of PPE, with a Safety Lead observing, will add some delays to the front-end processes, but these are essential to keeping providers safe. It is very plausible that, for example, door-to-needle/door-to-groin puncture times will be impacted. Similarly, at the point-of-care, a COVID-19–suspected patient going to imaging will result in having special precautions used in the scanner or neuroangiography suite, which will add additional time (for cleaning as well); this impacts scenarios with back-to-back code strokes as well.

Article Commentary: “Association of Blood Pressure During Thrombectomy for Acute Ischemic Stroke With Functional Outcome”

Adeola Olowu, MD

Maïer B, Fahed R, Khoury N, Guenego A, Labreuche J, Taylor G, et al. Association of Blood Pressure During Thrombectomy for Acute Ischemic Stroke With Functional Outcome: A Systematic Review. Stroke. 2019;50:2805–2812.

Greater than 50% of patients with successful recanalization are unable to regain functional independence at 3 months. There are several factors that contribute to the functional outcomes of patients who undergo mechanical thrombectomy; however, blood pressure is a prognostic factor that can be modulated (or managed).  This article addresses blood pressure management as a critical prognostic factor for outcome in acute ischemic stroke treated with mechanical thrombectomy. 

A systematic review of peri-procedural blood pressure values during mechanical thrombectomy was performed. A total of 9 studies out of 576 were eligible for systematic review after 2012. The 9 studies were comprised of 1 multicenter trial, 4 prospective trials, and 5 retrospective trials for a total of > 1000 patients. The systematic review revealed differences in how patient hemodynamics are being measured, as well as managed.

By |March 31st, 2020|clinical|0 Comments

Meet the Blogger: Rohan Arora, MD, FAHA

Rohan Arora

Name: Rohan Arora, MD, FAHA
Hometown: New Delhi, India
Current Position: Director of Stroke Program at LIJ Forest Hills, New York; Program Director, Vascular Neurology Fellowship, Zucker School of Medicine at Hofstra, Northwell, NY        

Q: What made you interested in a career in stroke?       

A: Finding myself in a position where my knowledge and expertise can save an individual from having permanent disability due to stroke is my constant motivation to practice this field. It could be a quick phone call/a telemedicine consult or long hours of ICU care; everything counts.

Q: What has been your career path into this field?

A: My focus is providing cutting edge clinical care, especially to young stroke patients, and enrolling patients in NIH-funded clinical studies and clinical trials. I am interested in finding novel methods to encourage people for a low-stress healthy lifestyle; that is one of the most commonly encountered risk factors for stroke and cerebrovascular disease.

By |March 25th, 2020|clinical|0 Comments

Author Interview: Dr. Eric Jouvent, MD, PhD, on “Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy”

Dr. Eric Jouvent
Dr. Eric Jouvent

A conversation with Dr. Eric Jouvent, MD, PhD, Professor of Neurology at Paris University. He is involved in acute stroke care in the stroke unit in Lariboisière Hospital in Paris. He holds a PhD in image processing.

Interviewed by Dr. Stephanie Lyden, MD, BS, a vascular neurology fellow at the University of Utah.

They will be discussing the article “Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy: Lessons From Neuroimaging.” Published in the January 2020 issue of Stroke, it is part of a Focused Updates in Cerebrovascular Disease series of articles on topics related to cerebral small vessel diseases.

Dr. Lyden: First of all, thank you for taking the time to discuss this important topic. What led you to become interested in studying CADASIL?

Dr. Jouvent: It was not really a choice at first. Residency in France is different than in the United States, where we first choose a city and then we move from department to department in that city. At the end of that time period, you hope to match in a department or with a team. At the end of my cycle, I matched with a team headed by Dr. Bousser, who identified the first family with CADASIL, in part because I was not only interested in stroke, but also in cognitive and behavioral alterations and in advanced MRI techniques, which are key aspects in small vessel diseases. This was how I started to become involved in CADASIL research.

Author Interview: Dr. Marco Pasi, MD, on “Clinical Relevance of Cerebral Small Vessel Diseases”

Dr. Marco Pasi and Prof. Charlotte Cordonnier
Dr. Marco Pasi and Prof. Charlotte Cordonnier

An interview with Dr. Marco Pasi, MD, Stroke Clinical Fellow at Université de Lille, CHU Lille, Inserm U1172, France, on his article “Clinical Relevance of Cerebral Small Vessel Diseases.” The article, co-authored by Prof. Charlotte Cordonnier, was published in the January 2020 issue of Stroke as part of a Focused Updates in Cerebrovascular Disease series of articles on topics related to cerebral small vessel diseases.

Interviewed by Dr. Parneet Grewal, MD, Vascular Neurology Fellow at Rush University Medical Center, Chicago, Illinois.

Dr. Grewal: First, I would like to thank Dr. Pasi and Pr. Cordonnier for agreeing to do this interview. This is an interesting paper which discusses in detail the main manifestations of cerebral small vessel disease (SVD) along with their impact. Can you please summarize the key findings of your paper and their application to clinical practice?

Dr. Pasi: Cerebral small vessel diseases (SVD) have gained increased interest in the last decades as they play a crucial role in a large variety of conditions, such as aging, stroke, cognitive impairment, and other age-related disabilities. The term SVDis used with various meanings according to the context, but from a neuropathological perspective, SVD describes a group of pathologies that affect the perforating arteries and arterioles located in the brain parenchyma or in the leptomeningeal vessels. Sporadic SVD is characterized by two main forms that mainly differ for their localization within the brain. The first one is arteriolosclerosis, also known as hypertensive-SVD, which has a predilection for the deep lenticulostriate arteries that are vulnerable to poorly controlled and long-standing hypertension or diabetes. The second most common form is cerebral amyloid angiopathy that is a pathological process characterized by the progressive accumulation of ß-amyloid protein in the wall of small cortical and leptomeningeal arterioles and arteries. It is clinically relevant to distinguish these two forms of SVD because they differ in terms of hemorrhagic risk with important consequences when antithrombotic decisions need to be taken. In our review, we aimed to provide a comprehensive overview of the main clinical manifestations of SVD that could help stroke physicians in their daily practice.

By |March 20th, 2020|clinical|0 Comments

Intra-Arterial Urokinase: Looking for the TICI 3

Elena Zapata-Arriaza, MD

Kaesmacher J, Bellwald S, Dobrocky T, Meinel TR, Piechowiak EI, Goeldlin M, et al. Safety and Efficacy of Intra-arterial Urokinase After Failed, Unsuccessful, or Incomplete Mechanical Thrombectomy in Anterior Circulation Large-Vessel Occlusion Stroke. JAMA Neurol. 2020;77:318–326.

Given the association among successful reperfusion and good functional outcomes, it is rational to look for tools that allow us to achieve the best TICI in patients undergoing mechanical thrombectomy. Within the ways to improve recanalization, we find the employment of safe and reliable devices with the ability to navigate more and more distally or the use of intra-arterial medication at the occlusion site. To determine the safety and efficacy of intra-arterial urokinase after failed or incomplete reperfusion in stroke mechanical thrombectomy(MT), Kaesmacher et al. performed an observational cohort study, with data collected from a prospective registry in a tertiary care stroke center from 2010-2017.

Primary safety outcome was the occurrence of symptomatic intracranial hemorrhage (sICH), and secondary endpoints included 90-day mortality and 90-day functional independence (defined as modified Rankin Scale score of 2). Efficacy was evaluated angiographically, applying the Thrombolysis in Cerebral Infarction (TICI) scale. Patients who were treated with intra-arterial urokinase (with or without intravenous tPA) only and patients presenting with posterior circulation large-vessel occlusion or distal anterior circulation vessel occlusions were excluded. Endovascular treatment was performed with second generation devices only, mostly stent retrievers. Urokinase was injected manually before or next to and distal to the thrombus, usually via the same microcatheter used to introduce the MT device. Final TICI grades were assessed by an independent researcher. When intra-arterial urokinase was administered after failed or incomplete MT, TICI grade was assessed before and after the intra-arterial urokinase administration. If no change occurred in TICI after urokinase administration, the rater had to assess whether any kind of angiographic improvement occurred compared with before administration of intra-arterial urokinase.

By |March 18th, 2020|clinical|0 Comments

Non-Contrast CT Signs for Acute Intracerebral Hematoma Expansion Prediction: Alternatives to Spot Sign

Piyush Ojha, MBBS, MD, DM

Law ZK, Ali A, Krishnan K, Bischoff A, Appleton JP, Scutt P, et al. Noncontrast Computed Tomography Signs as Predictors of Hematoma Expansion, Clinical Outcome, and Response to Tranexamic Acid in Acute Intracerebral Hemorrhage. Stroke. 2020;51:121–128.

Spontaneous intracerebral hemorrhage (ICH) remains a major cause of morbidity and mortality worldwide. Hematoma expansion affects 30-40% of patients with acute ICH within the first few hours of onset; hence, its prevention is an important treatment target in acute ICH care to prevent neurological worsening and poor long-term outcome, thus necessitating more close neurological monitoring. Although the presence of spot sign in Computed Tomography (CT) angiography predicts hematoma expansion, only a minority of ICH patients receives contrast injection during the initial imaging. Since non-contrast CT (NCCT) is widely available and used, NCCT markers represent an important alternative for prediction of hematoma expansion. 

NCCT signs can be divided into density markers (swirl sign, blend sign, black hole sign, hypodensity and fluid level) and shape markers (irregular shape, island sign and satellite sign).

Various observational studies, RCT populations and meta-analyses have suggested that NCCT signs markers might be reliable predictors of hematoma expansion and poor outcome in ICH, but with different effect size and strength of association.

Article Commentary: “Nonfocal Transient Neurological Attacks Are Associated With Cerebral Small Vessel Disease”

Richard Jackson, MD

Oudeman EA, Greving JP, Van den Berg-Vos RM, Biessels GJ, Bron EE, van Oustenbrugge R, et al. Nonfocal Transient Neurological Attacks Are Associated With Cerebral Small Vessel Disease. Stroke. 2019;50:3540–3544.

Oudeman et al. have published a paper on non-focal TIA’s which have been called transient neurological attacks (TNAs). As neurologists, we are always trained to localize first, but anyone who has taken stroke calls from the ER knows that not all the presentations and calls are localizable, such as those mentioned in this paper and described as “bilateral weakness, unsteadiness, or confusion.” In the introduction, the authors mention that these were historically thought to be secondary to hypoperfusion, but recent imaging have shown them to be associated with ischemia. Underlying risk factors are common to traditional TIA’s, such as smoking and hypertension, but not atherosclerotic disease or atrial fibrillation, which led to the current investigation for an association between small vessel disease and TNAs.