American Heart Association

author interview

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?

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.

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?

Author Interview: Mike Sharma, MD, MSc, FRCPC

Mike Sharma

Mike Sharma

A conversation with Mike Sharma, MD, MSc, FRCPC, Michael G. DeGroote Chair in Stroke Prevention and Associate Professor of Medicine (Neurology) at McMaster University/Population Health Research Institute and one of the co-authors of the COMPASS clinical trial, which studied the utility of combined low dose rivaroxaban and aspirin for cardiovascular disease prevention in patients with peripheral artery disease. Dr. Sharma presented a platform presentation on the findings of stroke prevention at the International Stroke Conference in February 2018 in Los Angeles, California.

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

They will be discussing the paper “Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease,” published in October 2017 in The New England Journal of Medicine (Eikelboom JW, et al. N Engl J Med 2017; 377:1319-30).

Saving Stroke Lives with EMS Prehospital Notification: Interview with Dr. Ethan Brandler

Dr. Ethan Brandler

Dr. Ethan Brandler

A conversation with Dr. Ethan Brandler, MD, MPH, FACEP, assistant professor of clinical emergency medicine at the State University of New York at Stony Brook, during the International Stroke Conference 2018 poster session.

Interviewed by Dr. Rohan Arora, MD, director of stroke fellowship at Hofstra Northwell School of Medicine.

How often does EMS call you before bringing a stroke patient to your center? How do you use that information to expedite stroke treatment? Wondering how EMS pre-notification can make a difference in your center’s outcomes?

Read this author interview for an update on how EMS triage can tremendously benefit patients with LVO (large vessel occlusions).

Author Interview: Dr. Greg Albers, on DEFUSE 3 and its Implications for Systems of Stroke Care in the U.S.

Dr. Greg Albers

Dr. Greg Albers

A conversation with Dr. Greg Albers, professor of neurology at Stanford and the principal investigator for DEFUSE 3.

Interviewed by Dr. Kaustubh Limaye, assistant professor of neurology in the division of cerebrovascular diseases at the University of Iowa, at the International Stroke Conference 2018 following the presentation of the final results of DEFUSE 3 and a simultaneous publication in the New England Journal of Medicine.

Albers GW, Marks MP, Kemp S, Christensen S, Tsai JP, Ortega-Gutierrez S, et al. Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging. New England Journal of Medicine. 2018

Dr. Limaye: Dr. Albers, first accept my hearty congratulations on the phenomenal success of the DEFUSE 3 trial.

Dr. Albers: Thank you so much.

Dr. Limaye: Just like everybody else, I was patiently waiting to hear what the results were going to be. All of us are delighted looking at the strong treatment effect that DEFUSE 3 showed in this extended time window. Thanks again for taking time out from your busy schedule. I’m sure this conference was extremely busy for you.

Dr. Albers: It’s been a very exciting week. We’ve been anticipating this for some time, and it’s wonderful to see this come to fruition.

The Future of Remote Ischemic Conditioning: An Interview with Dr. David Hess

International Stroke Conference
January 24–26

A conversation with David Hess, MD, vascular neurologist and Dean of the Medical College of Georgia, on Remote Ischemic Conditioning at the Internal Stroke Conference 2018.

Interviewed by Alexis N. Simpkins, MD, PhD, University of Florida.

Remote ischemic conditioning (RIC) was the focus of several talks and posters at the 2018 International Stroke Conference, focusing on the utility of RIC in a range of cerebrovascular disease from acute ischemic stroke, to small vessel disease, to subarachnoid hemorrhage. Remote ischemic conditioning involves temporarily decreasing blood flow typically to a limb such as the arm and then reperfusing the limb serially with the goal of creating a milieu in the blood that will mimic an ischemia tolerate state. The data presented summarized the most common adverse events and intolerances (skin petechia and pain in the extremity), feasibility in the clinical setting, and probably mechanism of action of RIC. Dr. David Hess participated in a question-and-answer interview following the conference about the future of RIC in the field of stroke.