American Heart Association

Monthly Archives: May 2018

National Stroke Awareness Month: Interview with Dr. Jaroslaw Aronowski

Dr. Jaroslaw Aronowski

Dr. Jaroslaw Aronowski

A conversation with Dr. Jaroslaw Aronowski, Professor, University of Texas HSC at Houston, McGovern Medical School, Department of Neurology, Vice Chair for Research, Roy M. and Phyllis Gough Huffington Chair in Neurology, and 2017 recipient of the Thomas Willis Award for his work on acute cerebral ischemia, intracerebral hemorrhage, and neuroinflammation, in recognition of National Stroke Awareness Month.

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

They will be discussing Dr. Aronowski’s career path and research, including his advice to young researchers and clinicians working in the field of stroke.

Dr. Simpkins: What drew you to the field of stroke and research early in your career?

Dr. Aronowski: Since my childhood, I was fascinated by the brain and by the complexity involved in how it works. My first steps with neuroscience were to work on opioids and mechanisms associated with opioid dependence. On this topic, over 30 years ago, we demonstrated that there could be a cross talk between the immune system and CNS that drives opioid dependency. It was rather unorthodox to connect CNS with the immune system these days. Looking back, it was an amazing environment at the University of Texas in Houston that triggered my interest and curiosity about stroke. This is primarily because of Jim Grotta, who just started developing his Stroke Program at UT. Together, with Grotta, about 30 years ago, I started to build my journey and adventure with translational stroke. All this happened during exciting days when we (the stroke community) have just started to investigate ideas that rt-PA could be used to treat stroke. Another important stimulus for me was daily interactions with many bright stroke fellows who rotated in the basic research lab and who brought great amount of energy, curiosity and translational value to the animal research as a model to test novel treatments for stroke. Lewis Morgenstern (later faculty in the department) was particularly an important contributor to my future interest in the pathogenesis of ICH.

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.

Interview: Authors of “Future of Animal Modeling for Poststroke Tissue Repair”

A conversation with Prof. Johannes Boltze, MD, PhD, from the University of Lübeck, Germany, along with co-authors Michel M. Modo, PhD; Jukka Jolkkonen, PhD; and Marietta Zille, PhD, regarding the future of animal modeling for poststroke tissue repair.

From left, Johannes Boltze, Michel M. Modo, Jukka Jolkkonen, and Marietta Zille.

From left, Johannes Boltze, Michel M. Modo, Jukka Jolkkonen, and Marietta Zille.

Interviewed by Shashank Shekhar, MD, MS, Vascular Neurology Fellow, University of Mississippi Medical Center.

They will be discussing the paper “Future of Animal Modeling for Poststroke Tissue Repair,” 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. Shekhar: First of all, I would like to thank Prof. Boltze and his co-authors for agreeing to do this interview. This is a very interesting paper where you have not only summarized the current animal research in tissue restoration and future trajectories in animal research for post-stroke repair, but also provided important strategies to overcome the hurdles in implementing successful and clinically relevant animal models.

Could you tell the readers why studying pre-clinical animal models for post-stroke tissue repair is important?

Dr. Boltze: True tissue repair, if it was achieved, will be a highly complicated endeavor that presumably requires numerous individual steps and the targeted modification of processes in the lesioned brain. Some of these processes may be currently unknown. Sophisticated in vitro systems, such as brain organoids, may be used to design intervention strategies towards a known mechanism on a cellular level, but the entire complexity of physiological and pathophysiological processes can only be studied in vivo so far.

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?

Getting at a Root Cause of Disparities with Hip-Hop Stroke

Neal S Parikh, MD
@NealSParikhMD

Williams O, Leighton-Herrmann Quinn E, Teresi J, Eimicke JP, Kong J, Ogedegbe G, et al. Improving Community Stroke Preparedness in the HHS (Hip-Hop Stroke) Randomized Clinical Trial. Stroke. 2018

Dr. Williams and colleagues recently published the results of their well-designed stroke education intervention study. I invite readers to consider and appreciate the merits of this study and this type of intervention.

Most patients with acute ischemic stroke are not treated with IV-tPA, and this is, in large part, due to delays to medical presentation. Universally, this is due to low awareness of stroke symptoms, and lack of awareness may magnify related disparities. The Hip-Hop Stroke program seeks to address this root cause issue by increasing awareness and stroke preparedness among children and their families through educational initiatives.

Extending Endovascular Therapy Treatment Time: Time to Face the Unmet Needs in Acute Stroke Care

Aristeidis H. Katsanos, MD

Jadhav AP, Desai SM, Kenmuir CL, Rocha M, Starr MT, Molyneaux BJ, et al. Eligibility for Endovascular Trial Enrollment in the 6- to 24-Hour Time Window: Analysis of a Single Comprehensive Stroke Center. Stroke. 2018

Results of the DAWN (Diffusion-Weighted Imaging or Computerized Tomography Perfusion Assessment With Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention With Trevo) and DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke-3) trials were incorporated into the recently published guidelines on acute ischemic stroke (AIS) management from the American Heart Association/American Stroke Association, which strongly suggest treatment with mechanical thrombectomy in patients with anterior circulation large vessel occlusion presenting within 6 to 16 hours of symptom onset, if satisfying DAWN or DEFUSE 3 eligibility criteria (Class of Recommendation: I, Level of Evidence A), while proposing treatment with mechanical thrombectomy in patients with anterior circulation large vessel occlusion within 6 to 24 hours of symptom onset, if eligible according to the criteria of the DAWN trial (Class of Recommendation: IIa, Level of Evidence B).

Intracranial Dolichoectasia vs. Intracranial Atherosclerosis

Deepak Gulati, MD

Zhai F-F, Yan S, Li M-L, Han F, Wang W, Zhou L-X, et al. Intracranial Arterial Dolichoectasia and Stenosis: Risk Factors and Relation to Cerebral Small Vessel Disease. Stroke. 2018

I would like to start by sharing a case recently presented to our hospital. A young woman presented with small midbrain stroke and is found to have eccentric subocclusive clot in top of basilar artery with dolichoectasia of the long segment involving from left V4 segment to bilateral posterior cerebral arteries and fusiform aneurysm of basilar artery. Unfortunately, she developed diffuse subarachnoid hemorrhage on day 3 of hospital course involving basal cisterns, leading ultimately to withdrawal of care by family. This case raised curiosity and frustration at the same time due to the lack of information on the natural course, prognosis, prevention and treatment of dolichoectasia. Hence, I chose to write this blog on this article with a focus on dolichoectasia.

Intracranial arterial dolichoectasia (IADE) is an arteriopathy characterized by abnormal elongation, tortuosity, and dilation of the cerebral arteries. IADE is present in about 12% of patients with stroke and affects the basilar artery in 80% of cases. IADE has various clinical presentations, ranging from asymptomatic to symptomatic with cranial nerve or brainstem compression, brain infarction, or intracranial haemorrhage. IADE has received little attention compared with other large vessel arteriopathies, such as intracranial atherosclerosis (ICAS). ICAS involves lipid infiltration and an inflammatory process of the arterial wall intima, whereas IADE involves rarefaction of the elastic tissue of the tunica media and fragmentation of the internal elastic lamina. This study aimed to investigate the risk factors of IADE and ICAS and explore the association of these two with different neuroimaging phenotypes of cerebral small vessel disease (CSVD), i.e. multilacunes, leukoaraiosis and état criblé.