American Heart Association

clinical

Migraine, PFO, and Ischemic Stroke – Is There a Relationship?

Sami Al Kasab, MD

West BH, Noureddin N, Mamzhi Y, Low CG, Coluzzi AC, Shih EJ, et al. Frequency of Patent Foramen Ovale and Migraine in Patients With Cryptogenic Stroke. Stroke. 2018

Recently, there has been increasing evidence of higher risk for stroke in patients with migraine, in particular with migraine with aura. Interestingly, patients with migraine with aura have higher rates of PFO with right to left shunt, bringing up the question: What’s the relationship between migraine with aura, PFO, and ischemic stroke?

In this study, West et al evaluate the prevalence of PFO with right to left shunt in patients with cryptogenic stroke and who had a history of migraine. This was a retrospective analysis of data on patients presenting to the UCLA comprehensive stroke center between January 2008 and November 2017. Stroke etiology was classified based on the ASCOD phenotyping. Patients’ charts were also reviewed to identify patients who carried a diagnosis of migraine. Patients with migraine auras for > 50% of the time were classified as migraine with frequent aura. A PFO with right to left shunt was identified by the presence of positive bubble contrast study with TTE, TEE, or TCD.

Article Commentary: “Dual Antiplatelet Therapy in Transient Ischemic Attack and Minor Stroke With Different Infarction Patterns”

Philip Chang, MD

Jing J, Meng X, Zhao X, Liu L, Wang A, Pan Y, et al. Dual Antiplatelet Therapy in Transient Ischemic Attack and Minor Stroke With Different Infarction Patterns: Subgroup Analysis of the CHANCE Randomized Clinical Trial. JAMA Neurol. 2018

In the setting of the new acute ischemic stroke guidelines this year, one of the new recommendations is a Class IIa, Level of Evidence B-R recommendation that treatment for 21 days with dual antiplatelet therapy (aspirin and clopidogrel) beginning within 24 hours for patients presenting with minor stroke can be beneficial for early secondary prevention for a period up to 90 days from symptom onset. This recommendation was based solely off the CHANCE trial. In the original CHANCE cohort, they found that DAPT reduced stroke recurrence by about 30%.

In Search for a Potential Biomarker for Small Vessel Disease: Is Plasma Aβ Level the Answer?

Shashank Shekhar, MD, MS
@Artofstroke

van Leijsen EMC, Kuiperij HB, Kersten I, Bergkamp MI, van Uden IWM, Vanderstichele H, et al. Plasma Aβ (Amyloid-β) Levels and Severity and Progression of Small Vessel Disease. Stroke. 2018

Leukoaraiosis, along with microbleeds and lacunes, are one of the most commonly encountered findings after a brain imaging in patients with multiple vascular risk factors. These changes are a result of small vessel disease (SVD). White matter disease is considered as a potential imaging marker for the development of dementia. Apart from traditional risk factors, e.g., hypertension, diabetes, etc., Aβ (amyloid β) has been proposed as an additional contributor to SVD. To investigate the association of plasma Aβ levels with severity and progression of SVD, the authors studied 487 participants in a prospective cohort RUN DMC study (Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Imaging Cohort).

Using MRI-based Techniques for Easier Recognition of Hemodynamic Failure in Chronic Cerebrovascular Steno-Occlusive Disease

Gurmeen Kaur, MBBS
@kaurgurmeen

Fierstra J, van Niftrik C, Warnock G, Wegener S, Piccirelli M, Pangalu A, et al. Staging Hemodynamic Failure With Blood Oxygen-Level–Dependent Functional Magnetic Resonance Imaging Cerebrovascular Reactivity: A Comparison Versus Gold Standard (15O-)H2O-Positron Emission Tomography. Stroke. 2018

A major challenge faced by vascular neurologists and neuro-radiologists is accurately identifying the subset of patients with chronic cerebrovascular steno-occlusive disease, predicting those that have a propensity to develop hemodynamic failure and, as a result, have an increased risk of stroke.

Over the past few years, with development of imaging technology, multiple CT and MRI-based techniques have been developed to assess the degree of hemodynamic failure. Cerebral blood flow measurement using 15O PET scan has been recognized as the gold standard. There is a baseline measurement followed by a second scan with acetazolamide (Diamox) challenge.

Author Interview: Dr. Bruce Campbell, on the EXTEND-IA TNK trial

Dr. Bruce Campbell

Dr. Bruce Campbell

A conversation with Dr. Bruce Campbell, MBBS (Hons), BMedSc, PhD, FRACP, co-principal investigator of the EXTEND-IA TNK trial and Head of Stroke at Royal Melbourne Hospital, University of Melbourne, about EXTEND-IA TNK and its implications for stroke care.

Interviewed by Kaustubh Limaye, MD, an Assistant Professor in the Division of Cerebrovascular Diseases at the University of Iowa (@kaustubhslimaye).

They will be discussing the article “Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke,” published in The New England Journal of Medicine.

EXTEND-IA TNK randomized 202 ischemic patients with large vessel occlusion 1:1 between 0.25mg/kg tenecteplase and 0.9mg/kg alteplase prior to endovascular thrombectomy. The proportion of patients who had substantial (>50%) reperfusion or no retrievable thrombus on the initial angiographic assessment was approximately doubled in the tenecteplase group (22% vs. 10%), which met the non-inferiority threshold (p=0.002) and was indeed superior (p=0.03) to alteplase. Functional outcomes at day 90 were also significantly improved in the tenecteplase group in ordinal (shift) analysis of the modified Rankin Scale. Symptomatic intracerebral hemorrhage occurred in 1/101 patients in each group.

Dr. Limaye: First, accept my heartiest congratulations for the completion and success of the EXTEND-IA TNK trial. I think the results will benefit acute stroke patients with large vessel occlusion and open up more avenues in streamlining care of such patients. Would you like to share with our readers the timeline of this trial – from conceptualization to execution?

Author Interview: Dr. Lawrence Wechsler, MD

Dr. Lawrence Wechsler

Dr. Lawrence Wechsler

A conversation with Dr. Lawrence Wechsler, MD, Henry B. Higman Professor and Chair, Department of Neurology, University of Pittsburgh Medical School, about the role of cell therapy in chronic stroke.

Interviewed by Deepak Gulati, MD, Assistant Professor of Neurology, Ohio State University.

They will be discussing the paper “Cell Therapy for Chronic Stroke,” published in the May issue of Stroke. The article is part of a Focused Update in Cerebrovascular Disease centered on stem cells and cell-based therapies.

Dr. Gulati: Can you please summarize in simple words the mechanism of action of stem cell therapy in chronic stroke? Also, what are your thoughts on the modes of administration?

Dr. Wechsler: In chronic stroke, the most likely mechanism is paracrine release of growth factors and cytokines that act locally to promote functional recovery. These factors increase neurogenesis, synaptogenesis, angiogenesis and reduce inflammation. It is not known which of these processes is most important, and the pleomorphic effects of cell therapy make cell therapy an attractive approach in chronic stroke. Stereotactic implantation of cells in chronic stroke is most likely to be beneficial to assure delivery of cells to the area of injury in this late stage at a time when disruption of the BBB or homing signals are not operative to allow cells to reach the infarct area by other modes of delivery.

Author Interview: Dr. Zaal Kokaia, PhD

Dr. Zaal Kokaia

Dr. Zaal Kokaia

A conversation with Dr. Zaal Kokaia, PhD, Professor of Experimental Medical Research and the Head of the Laboratory of Stem Cells & Restorative Neurology at the Lund University Stem Cell Center in Sweden.

Interviewed by Gurmeen Kaur, MBBS, Vascular Neurology Fellow, Icahn School of Medicine at Mount Sinai.

They will be discussing the paper “Customized Brain Cells for Stroke Patients Using Pluripotent Stem Cells,” published in the May issue of Stroke. The article is part of a Focused Update in Cerebrovascular Disease centered on stem cells and cell-based therapies.

European Stroke Organisation Conference 2018: Insights from the Large Clinical Trials Session

European Stroke Organisation Conference
May 16–18, 2018

Aristeidis H. Katsanos, MD, PhD

Dr. Robert Hart presented the first results of the NAVIGATE ESUS trial, a randomized clinical trial (RCT) on the safety and efficacy of Rivaroxaban 15mg once daily compared to acetylsalicylic acid (ASA) 100mg in patients with embolic strokes of undetermined source (ESUS). The trial was stopped prematurely at the second interim analysis, and after randomization of a total of 7213 patients, due to the absence of significant differences between the two groups regarding the primary efficacy outcome of all recurrent stroke or systemic embolism. Moreover, a significant increase in the risk of both hemorrhagic stroke and all major bleeding events was found in the Rivaroxaban group compared to the ASA group. Although no significant differences were found in other pre-specified subgroup analyses, a subgroup analysis of patients with patent foramen ovale randomized within the NAVIGATE ESUS trial presented by Dr. Scott Kasner suggests that Rivaroxaban treatment may reduce the risk of recurrent cerebral ischemic events in this specific patient population compared to ASA.

Tranexamic Acid for Acute Intracerebral Hemorrhage

European Stroke Organisation Conference
May 16–18, 2018

Andrea Morotti, MD

The results of the Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage (TICH-2) randomized controlled trial were presented at the 4th congress of the European Stroke Organisation in Gothenuburg, Sweden. Subjects with primary, spontaneous intracerebral hemorrhage (ICH) presenting within 8 h from symptom onset/last time seen well were randomized to treatment with intravenous tranexamic acid (1 g bolus followed by 1 g over an 8 h infusion) versus placebo. 1 The main outcomes of interest were hematoma expansion (defined as absolute hemorrhage growth>6mL or relative hemorrhage growth>33% from baseline volume) and the proportion of patients with death or severe disability at 3 months from the index event.

Author Interview: Dr. Michael Chopp, PhD

Dr. Michael Chopp

Dr. Michael Chopp

A conversation with Dr. Michael Chopp, PhD, Vice Chairman, Department of Neurology, Scientific Director, Neurosciences Institute, Zoltan J. Kovacs Chair in Neuroscience Research at Henry Ford Hospital, and Distinguished Professor of Physics, Oakland University, about the novel use of exosomes and miRNA as possible therapeutic agents in stroke patients.

Interviewed by Alexis N. Simpkins, MD, PhD, Assistant Professor of Neurology, University of Florida School of Medicine.

They will be discussing the paper “Exosome Therapy for Stroke,” published in the May 2018 issue of Stroke. The article is part of a Focused Update in Cerebrovascular Disease centered on stem cells and cell-based therapies.

Dr. Simpkins: Exosomes appear to be a promising new therapeutic target for stroke given their ability to potentially help with neuroplasticity and vascular remodeling. Changes in the blood induced by acute stroke can be rapid. How quickly does the concentration and content of exosomes change? Do you foresee exosome therapy being best used in the acute treatment of stroke or in subacute phase during stroke recovery?

Dr. Chopp: Exosomes are exceptionally potent mediators of biological function. Exogenously administered exosomes interact with parenchymal and endothelial cells. They contain protein. RNA, and lipid cargo that are highly efficiently delivered to receptive cells. The exosomes also may contain molecular machinery to facilitate and amplify biological function of the delivered cargo. Particularly important is the microRNA (miR) content of the exosomes. miRs are master switches, and each miR can potentially impact and modulate the translation of hundreds of genes. The nanometer dimension of exosomes and their cell surface receptors facilitate their entry into the brain and their ability to permeate the central nervous system. In addition, absorbed exosomes induce a sequential chain reaction release of exosomes from target cells that further amplifies their biological function. Thus, although the numbers of administered exosomes are clearly diluted after intravascular administration, exosomal content, and specifically their miR content, as well as subsequent releases of secondary exosomes, greatly amplify exosome function. I do foresee the use of exosomes in both the treatment of acute stroke, as well as in subacute and chronic stroke. Harnessing the potential of exosomes, endogenous mediators of nearly all cell and inter-organ communication, hopefully, will lead to efficacious neurovascular protective and restorative therapies for stroke, neural injury and neurodegenerative diseases. The question should not be whether exosome therapy is best used in the acute or chronic treatment of stroke. What has to be asked is, what are the optimal exosome therapies for acute and for chronic treatment of stroke?