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Thrombus Migration in Large Vessel Occlusion: Is it Good or Bad?

Ravinder-Jeet Singh, MBBS, DM

Alves HC, Treurniet KM, Jansen IGH, Yoo AJ, Dutra BG, Zhang G, et al. Thrombus Migration Paradox in Patients with Acute Ischemic Stroke. Stroke. 2019; 50:3156-3163.

Thrombus is a dynamic structure with constantly changing size, morphology and location over time, to variable extent in each patient, before recanalization occurs. Recently, there is interest in understanding dynamic clot features, especially regarding thrombus movement — defined as change in the occlusion site — between initial (typically CT angiogram) and follow-up vascular imaging (usually catheter angiogram for mechanical thrombectomy). Whether thrombus migration before recanalization is of any clinical or functional significance remains under investigation. The thrombus migration was studied in the past.1 It underlies a clinical phenomenon called “spectacular shrinking deficit,” in which a patient with major hemispheric syndrome shows rapid (over minutes to hours) and dramatic improvement or disappearance of most clinical deficits.1 Use of regular “vascular imaging” now allows investigating the concept in reverse order, i.e., the incidence thrombus migration and correlate it with clinical change or functional outcome. Different factors determine the dynamic behavior of the clot, including source of thrombus (etiology of stroke), composition of the thrombus, initial thrombus location within arterial tree (for example, proximal vs distal occlusion), angioarchitecture around the thrombus and use of intravenous thrombolysis (IVT).1-4

Orai2 Mediates Protection From Ischemia-Induced Capacitative Calcium Entry in Neurons

Melissa Trotman-Lucas, PhD
@TrolucaM

Stegner D, Hofmann S, Schuhmann MK, Kraft P, Herrmann AM, Popp S, et al. Loss of Orai2-Mediated Capacitative Ca2+ Entry Is Neuroprotective in Acute Ischemic Stroke. Stroke. 2019;50:3238–3245.

Neuroprotective treatments aim to prevent cellular death, particularly neuronal cell death, during ischemic/hypoxic conditions such as in acute ischemic stroke. Maintenance of neuroprotection long-term requires a return of blood and oxygen to the ischemic territory area, not regularly achieved in previous clinical trials. Yet, with recanalization rates of greater than 80%, afforded by the advent of mechanical thrombectomy following ischemic stroke, the return of flow to the ischemic territory is now more consistent. Nevertheless, following the return of blood flow to this area, cellular damage continues to spread and grow due to the phenomenon of “ischemic-reperfusion injury.” This progressive increase in damage indicates a continued need to investigate neuroprotective treatments that could be used alongside recanalization, both thrombolysis and thrombectomy, to recover/prevent long-term cellular damage.

It is well established that calcium (Ca2+) overload plays a key role in neuronal death during ischemic/hypoxic events. In addition to voltage-gated and receptor-mediated Ca2+ influx, there is a further route of entry into the cell, a route switched on in response to depleted intracellular Ca2+ stores. This additional entry route is called capacitative or store operated Ca2+ entry and is thought to contribute to the stabilization of both cytosolic Ca2+ concentration and intracellular Ca2+ stores.

Author Interview: Profs. Eric E. Smith and Hugh Markus on “New Treatment Approaches to Modify the Course of Cerebral Small Vessel Diseases”

Professor Eric E. Smith and Professor Hugh Markus
Prof. Eric E. Smith and Prof. Hugh Markus

A conversation with Professor Eric E. Smith, MD, Ph.D., Professor of Neurology, Cumming School of Medicine, University of Calgary, Canada, and Professor Hugh Markus, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.

Interviewed by Shashank Shekhar, MD, MS, Assistant Professor, Division of Vascular Neurology, University of Mississippi Medical Center, USA; @ArtofStroke.

They will be discussing the article “New Treatment Approaches to Modify the Course of Cerebral Small Vessel Diseases,” published in the January 2020 issue of Stroke. The article is part of a Focused Updates in Cerebrovascular Disease series of articles on topics related to cerebral small vessel diseases.

Dr. Shekhar: I would like to thank Prof. Smith and Prof. Markus for agreeing to do this interview. In this interesting review paper, you have discussed in detail the new treatment approaches to modify the course of small vessel disease. Could you tell the readers why you decided to write about this topic?

Prof. Smith: Cerebral small vessel disease is a common condition of aging. We now know that it can cause cognitive decline and stroke. When I chaired a writing group for the American Heart Association that produced a scientific statement on stroke prevention in persons with silent cerebrovascular disease (Smith et al, Stroke 2017; 48:e44-e71), one of the interesting things we found is that there were few clinical trials that focused on small vessel disease. There are no medications specifically indicated for cerebral small vessel disease. The time seemed ripe to review progress in this area, and indeed we found emerging evidence for new treatment strategies in early phase trials.

Prof. Markus: Cerebral small vessel disease is an enormous health problem — it causes a quarter of all strokes and is the most common cause of vascular dementia. Despite this, there are few, if any, treatments for established disease, and it remains one of the great therapeutic challenges in stroke. We wanted to summarize where we were and describe a pathway forwards.

Meet the Blogger: Shashank Shekhar, MD, MS

Shashank Shekhar

Name: Shashank Shekhar, MD, MS
Hometown: Jackson, MS, USA
Current Position: Assistant Professor, StrokeNet Co-PI, University of Mississippi Medical Center
Twitter: @artofstroke

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

A: I was always interested in neurosciences. While I was doing my master’s thesis on a stroke topic, I had the opportunity to do a clinical rotation in a stroke unit at Helsinki University Central Hospital, Finland, with an excellent door to need time averaging 20 minutes. By that time, I had a solid understanding of basic science and clinical knowledge of stroke, but I was not exposed to the real-time workflow leading to thrombolysis. I get to learn the process from beginning to end, including aftercare of the stroke patient all the way to discharge. The experience was extremely fascinating and immersive. That’s when I decided that I will do vascular neurology.

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

A: I received my medical degree from Government Medical College & Hospital in Chandigarh, India. Soon after, I pursued a master’s degree in neurosciences from the University of Helsinki in Finland. I was involved in several basic stroke research projects at Helsinki University Central Hospital, and later, the clinical birth cohort project (FinnBrain) studying cognition in infants using Near-Infrared Spectroscopy at the University of Turku. I moved to the USA for the neurology residency, followed by a Vascular Neurology fellowship at the University of Mississippi Medical Center (UMMC), where I am currently working as an Assistant Professor. I am active in various clinical projects as PI and StrokeNet co-PI for the UMMC satellite center. I have a particular interest in neurocognition and the identification of biomarkers for acute ischemic stroke. I am also heavily involved in research education for residents and fellows.

By |February 3rd, 2020|clinical|0 Comments

Good Collaterals Despite Low ASPECTS: Expanding Thrombectomy Candidates

Elena Zapata-Arriaza, MD
@ELeNaZapS

Broocks G, Kniep H, Schramm P, Hanning U, Flottmann F, Faizy T, et al. Patients with low Alberta Stroke Program Early CT Score (ASPECTS) but good collaterals benefit from endovascular recanalization. J Neurointerv Surg. 2019.

The primary therapeutic target of mechanical thrombectomy defined by the salvageable tissue at risk is minimized in patients with low Alberta Stroke Program Early CT Score (ASPECTS). In contrast, the risk of developing malignant infarctions is maximized in patients with a large early ischemic core, which can lead to severe complications by progressive ischemic edema within the first days after stroke onset. Low ASPECTS (≤5) still represents a limitation for stroke thrombectomy performance. But what happens in those patients with low ASPECTS and good collaterals after endovascular treatment? Do these cases have the potential to achieve good functional results? Broocks and colleagues have employed these questions as the starting point in the present paper.

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

Meet the Blogger: Lina Palaiodimou, MD

Lina Palaiodimou

Name: Lina Palaiodimou, MD
Hometown: Athens, Greece
Current Position: Neurologist, Second Department of Neurology, “Attikon” University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

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

A: Until the recent past, the following playful dogma prevailed: “Neurologists know everything, but do nothing.” Stroke and the recent therapeutic advances regarding acute treatment really changed that scenery. Rapid information processing, accurate critical thinking, effective cooperation, and, of course, the adrenaline rush constitute the core of acute stroke management and actually describe my dream job. So, when I first got involved with an acute stroke patient being thrombolyzed and getting dramatically better, I was determined that a stroke career would suit me. That has not changed a bit since then.   

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

A: I graduated from Medical School, Aristotle University of Thessaloniki, in Greece, and the Military Medical Academy in Thessaloniki, Greece. In late 2019, I completed the neurology residence in Attikon University General Hospital of Athens. Currently, I am a PhD student in Medical School, National and Kapodistrian University of Athens, and my thesis is focused on stroke management and prognosis. I am also working with a team of dedicated stroke neurologists in the Division of Cerebrovascular Diseases of Attikon University General Hospital of Athens, where more than 600 stroke patients are being evaluated per year, in an inpatient and outpatient setting.

By |January 28th, 2020|clinical|0 Comments

PICASSO Trial: The Shades of Anti-Platelets

Rachel Forman, MD

Kim BJ, Kwon SU, Park J-H, Kim Y-J, Hong K-S, Wong LKS, et al. Cilostazol Versus Aspirin in Ischemic Stroke Patients With High-Risk Cerebral Hemorrhage: Subgroup Analysis of the PICASSO Trial. Stroke. 2019.

One of the most common discussions on any given stroke service involves the balance of preventing ischemic strokes (IS) and preventing intracranial hemorrhage (ICH). Whether it is about resuming anticoagulation in a hemorrhage patient or resuming aspirin in a patient with cerebral amyloid angiopathy there is always much debate on timing and decisions.  The decision to resume aspirin in a patient with an MRI full of cerebral microbleeds (CMBs) is often difficult. This paper looks into an alternative agent, cilostazol, for reducing hemorrhage risk in patients who warrant anti-platelet therapy. The background of the study is that cilostazol has shown to have less hemorrhagic events than aspirin among patients with ischemic stroke. 

The PICASSO trial (Prevention of Cardiovascular Events in Asian Ischemic Stroke Patients with High Risk of Cerebral Hemorrhage) was an Asian trial that aimed to determine which antiplatelet agent is more effective and safe in patients with prior hemorrhagic stroke or multiple CMBs. Cilostazol is an antiplatelet agent with additional vasodilatory effects. The trial, published in 2018, showed that cilostazol was noninferior to aspirin in preventing a composite of major vascular events; however, it failed to reduce ICH. This paper reviews the subgroup analysis to identify patients who would show greater benefit with cilostazol. 

Meet the Blogger: Piyush Ojha, MBBS, MD, DM

Dr. Piyush Ojha

Name: Dr. Piyush Ojha, MBBS, MD, DM
Hometown: Neemuch, Madhya Pradesh, India
Current Position: Stroke Neurologist, Jabalpur, Madhya Pradesh, India

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

A: During my neurology residency, I attended the World Stroke Congress held in Hyderabad, India, where I presented two papers. I also got a chance to meet some of the best brains working in the field of stroke. Looking at the recent developments in the area of stroke over the last five years, I was inclined towards making stroke my future career.

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

A: After finishing my neurology residency, I worked at a hospital at Jabalpur, India, where I tried to create stroke awareness by conducting many talks and public awareness programs. Then, I was lucky enough to be selected as a stroke fellow with the prestigious Calgary Stroke Program, where I got an opportunity to work with an excellent team of dedicated stroke neurologists and fellows.

By |January 24th, 2020|clinical|0 Comments

Meet the Blogger: Melissa Trotman-Lucas, PhD

Name: Dr. Melissa Trotman-Lucas, PhD
Hometown: Nottingham, England, UK
Current Position: Research Fellow, University of Nottingham, UK

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

A: As an undergraduate at the University of Leicester, I studied biological sciences. A significant part of this course involved an in-depth look at brain function and, conversely, its dysfunction. I enjoyed thinking about cellular physiology and how functioning is impacted following the smallest of changes. When [there was] a PhD opportunity to study the role of excitotoxicity in the pathological damage that occurs following ischemic stroke, I was excited to investigate this and better understand it. A close family member of mine had suffered multiple strokes, so I knew the impact this debilitating disease could have on an individual, but also to the surrounding family. So, for me, to work even in the smallest way towards improving treatment and recovery for stroke sufferers was of a keen interest for me.

By |January 22nd, 2020|clinical|0 Comments

Article Commentary: “Effect of Heart Rate on Stroke Recurrence and Mortality in Acute Ischemic Stroke With Atrial Fibrillation”

Alan C. Cameron, BSc (Hons), MB ChB, PhD, MRCP

Lee K-J, Kim BJ, Han M-K, Kim J-T, Choi K-H, Shin D-I, et al. Effect of Heart Rate on Stroke Recurrence and Mortality in Acute Ischemic Stroke With Atrial Fibrillation. Stroke. 2020;51:162–169.

Atrial fibrillation (AF) is a common comorbidity in patients with acute ischaemic stroke and a dilemma frequently encountered in clinical practice is whether we should aim for stringent or lenient rate control in patients with AF. Lee and colleagues sought to address this question by assessing associations between mean heart rate, heart rate variability and clinical outcomes in more than 2,000 patients with acute ischaemic stroke and AF included in a prospective, multi-centre, Korean-based stroke registry. The authors demonstrate a J-shaped association between heart rate and mortality, with heart rates in the region of 80 beats per minute associated with lowest risk of mortality at 24 hours or 3 to 7 days after stroke onset and heart rates above or below this sweet-spot associated with increased mortality. Similar results were observed for a composite endpoint of stroke recurrence, myocardial infarction and all-cause mortality, although no effect was observed on stroke recurrence alone, nor from heart rate variability on mortality, stroke recurrence or the composite endpoint. 

By |January 21st, 2020|clinical|0 Comments