American Heart Association

author interview

Author Interview: Dr. Diogo Haussen, MD, and Dr. Thomas Madaelil, MD, on “Multimodality Imaging in Carotid Web”

Dr. Diogo Haussen, left, and Dr. Thomas Madaelil

Dr. Diogo Haussen, left, and Dr. Thomas Madaelil

A conversation with Dr. Diogo Haussen, MD (Assistant Professor of Neurology, Emory School of Medicine/Grady Memorial Hospital), and Dr. Thomas Madaelil, MD (Neurointerventional Fellow, Emory School of Medicine), on imaging and clinical significance of carotid web.

Interviewed by Sami Al Kasab, MD (StrokeNet fellow, University of Iowa Hospitals and Clinics).

They will be discussing the paper “Multimodality Imaging in Carotid Web,” published in Frontiers in Neurology.

Dr. Al Kasab: I read with great enthusiasm your recent article comparing different imaging modalities to diagnose a carotid web. Can you please summarize the key findings of your study, and how your results can be applied to our clinical practice?

Drs. Haussen and Madaelil: Thank you for your interest in our manuscript. Acute ischemic stroke is commonly a devastating condition, especially when occurring in young adults. Occasionally, we can get tangled when we cast wide nets for the diagnostic work-up in patients with cryptogenic stroke. Carotid web is a condition that can be overlooked when neurovascular studies are reviewed during this diagnostic work-up period, and it may actually be more common that previously thought. Our study is aimed to help shed light on the performance of different imaging modalities in the diagnosis of carotid web, which is particularly important since there were no previously published comparative studies. We observed that computed tomographic angiogram (CTA) shared very high rates of inter-rater agreement with digital subtraction angiogram (DSA), while the CTA agreement with ultrasonography was much more limited. Therefore, non-invasive multiplanar imaging modalities, such as CTA, should be considered in the evaluation of young patients with otherwise no identified stroke cause considering the possibility of an underlying carotid web.

Author Interview: Drs. Thabele (Bay) Leslie-Mazwi, MD, and Gregory W. Albers, MD, on “DEFUSE 3 Non-DAWN Patients: A Closer Look at Late Window Thrombectomy Selection”

Dr. Thabele (Bay) Leslie-Mazwi, left, and Dr. Gregory W. Albers

Dr. Thabele (Bay) Leslie-Mazwi, left, and Dr. Gregory W. Albers

An interview with Dr. Thabele (Bay) Leslie-Mazwi, MD, Director of Endovascular Stroke Services, Massachusetts General Hospital; Assistant Professor of Neurology, Harvard University; and Dr. Gregory W. Albers, MD, Director, Stanford Stroke Center; Professor of Neurology, Stanford University.

Interviewed by Kristina Shkirkova, BSc, Doctoral Student in Neuroscience, Department of Neurosurgery, Zilkha Neurogenetic Institute, University of Southern California.

They will be discussing the article “DEFUSE 3 Non-DAWN Patients: A Closer Look at Late Window Thrombectomy Selection,” published in the March 2019 issue of Stroke.

Ms. Shkirkova: Please briefly summarize the design and findings of your study.

Drs. Leslie-Mazwi and Albers: We evaluated DEFUSE 3 patients who would have been excluded from the DAWN trial based on DAWN eligibility criteria, with the goal of assessing treatment effect in that DEFUSE 3 subgroup (DEFUSE 3 Non-DAWN). The main reasons for DEFUSE 3 Non-DAWN were NIHSS 6-9, core too large (based on age and volume of established infarct), and mRS of 2. Patients with mRS 2 were included with the NIH stroke scale 6-9 group, as detailed in our paper, and so we analyzed the DEFUSE 3 Non-DAWN patients NIHSS 6-9 and core-too-large patients to assess treatment effect in that subgroup.

Patients with pretreatment core infarct volumes <70ml but too large for inclusion by DAWN criteria demonstrated robust benefit from endovascular therapy. Data supporting a beneficial treatment effect across the full range of NIHSS scores was documented in the entire DEFUSE 3 population. In our small subgroup of patients with NIHSS 6-9, we found a trend towards benefit.

Author Interview: Prof. Craig Anderson, MD, PhD, on “Intensive blood pressure reduction with intravenous thrombolysis therapy for acute ischaemic stroke (ENCHANTED)”

Prof. Craig Anderson

Prof. Craig Anderson

An interview with Prof. Craig Anderson, MD, PhD, Professor of Neurology and Epidemiology, University of New South Wales, about blood pressure management after intravenous thrombolysis treatment.

Interviewed by Dr. Mohammad Anadani, MD, Neurology Resident, Medical University of South Carolina.

They will be discussing the paper Intensive blood pressure reduction with intravenous thrombolysis therapy for acute ischaemic stroke (ENCHANTED): an international, randomised, open-label, blinded-endpoint, phase 3 trial, published in the February 2019 issue of The Lancet.

Dr. Anadani: First, I want to thank Prof. Anderson for agreeing to the interview. Prof. Anderson’s research has a significant impact on the stroke field and especially on our understanding of the relationship between blood pressure and outcome after hemorrhagic and ischemic stroke. Prof. Anderson was the lead investigator of the INTERACT 2 trial and the ENCHANTED trial. In this interview, we will discuss the results of the ENCHANTED trial and its implication on clinical practice.

Author Interview: Dr. Raul Nogueira, MD, on “Mechanical Thrombectomy in Patients With Milder Strokes and Large Vessel Occlusions”

Dr. Raul Nogueira

Dr. Raul Nogueira

A conversation with Raul Nogueira, MD, Professor of Neurology, Neurosurgery and Radiology,Emory University School of Medicine, Director of Neuroendovascular Service, Marcus Stroke & Neuroscience Center, Grady Memorial Hospital, on endovascular thrombectomy for acute ischemic stroke with mild symptoms.

Interviewed by Mark R. Etherton, MD, PhD, Assistant in Neurology, Massachusetts General Hospital, Instructor, Harvard Medical School.

They will be discussing the paper “Mechanical Thrombectomy in Patients With Milder Strokes and Large Vessel Occlusions: A Multicenter Matched Analysis,” published in the October 2018 issue of Stroke.

Dr. Etherton: This is a very interesting paper that I think raises some good questions about the triage and management approaches to patients with large vessel occlusions and low severity ischemic strokes as assessed with the NIHSS. Could you speak a little bit regarding your management approaches to this patient population, including if any differences whether the stroke was involving the anterior or posterior circulation?

Dr. Nogueira: The first thing you have to acknowledge is there is not a lot of data to answer this question. The data is mostly retrospective in nature. There are methodological issues with these retrospective approaches in that you have to analyze them as intention-to-treat. So you have to separate out the cohorts as immediate treatment versus no immediate treatment. In reality, you really have three groups: immediate mechanical thrombectomy (MT), immediate medical therapy, and immediate medical therapy with subsequent deterioration and rescue MT. You cannot group this last group with the MT group because your initial intent was to treat this group medically. This is the equivalent of cross-over in a clinical trial which creates methodological problems.

Author Interview: Prof. Turgut Tatlisumak, MD, PhD, on “Nontraumatic intracerebral haemorrhage in young adults”

Prof. Turgut Tatlisumak

Prof. Turgut Tatlisumak

A conversation with Turgut Tatlisumak, MD, PhD, from the Department of Clinical Neuroscience and Neurology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.

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

They will be discussing the article “Nontraumatic intracerebral haemorrhage in young adults,” published in Nature Reviews Neurology.

Dr. Shekhar: First, I would like to thank Prof. Tatlisumak for agreeing to do this interview. This is an interesting review paper in which you have discussed in detail nontraumatic intracerebral hemorrhage (ICH) in young adults. Could you tell the readers why you decided to write about hemorrhage in young adults?

Prof. Tatlisumak: We have long been investigating stroke in young adults, but most of our attention went to ischemic strokes. I wished to extend our research to ICH in young adults and found only few original patient series. Sometime later, I noticed that there is not a single review on this topic, and there is an unmet need. Then we set up a small group of experts sharing the tasks. That is how we started.

Interview: Authors of “Intra-Arterial Delivery of Cell Therapies for Stroke”

A conversation with Dr. Raphael Guzman, Professor of Neurosurgery and Neurosciences at University Hospital Basel; Dr. Miroslaw Janowski, Associate Professor of Radiology at the Johns Hopkins University School of Medicine; and Dr. Piotr Walczak, Associate Professor of Radiology at Johns Hopkins University.

Dr. Raphael Guzman, Dr. Miroslaw Janowski, Dr. Piotr Walczak

From left, Dr. Raphael Guzman, Dr. Miroslaw Janowski, and Dr. Piotr Walczak.

Interviewed by Dr. Kaustubh Limaye (@kaustubhslimaye), Assistant Professor of Neurology in the division of Cerebrovascular Diseases at the University of Iowa.

They will be discussing the paper “Intra-Arterial Delivery of Cell Therapies for 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. Limaye: I read your review in Stroke that deals with intra-arterial cell therapy for stroke recovery with great interest and enthusiasm. Can you summarize the important points of your article for our readers?

Authors: The concept of using stem cells as a strategy for treatment of stroke is a few decades old. There were hundreds of animal studies, dozens of clinical trials, and we are still far from effective therapy. Perhaps it is time to take a step back and think whether something has to be changed with the approach to developing cell therapy for stroke. One problem is that we scientists and clinicians have been overly optimistic or even ignorant. The typical approach for research on stem cell-based therapies was: Let’s inject some cells into the brain lesion and hope for the best. The challenge was immense as the stem cells of choice after transplantation are required to find their way migrating to the target, survive, proliferate, appropriately differentiate and exert therapeutic effect. We see first-hand that such a simplistic approach was not constructive. While open label preclinical studies were optimistic, practically all rigorous clinical trials failed to demonstrate satisfactory therapeutic effects. This status quo has hurt the field of stem cell therapy for stroke as scientists, grant reviewers and funding agencies gradually lose enthusiasm and abandon the concept of brain regeneration after stroke with stem cells, stifling any further progress. It is urgent that we work towards reversing that trend, and our strategy is to shift from a “do all” approach to addressing very basic challenges in a systematic manner. After identifying promising and highly potent sources of stem cells, which is now largely accomplished, the next step is to develop methods for effective and safe delivery of stem cells to the site of brain injury.

Author Interview: Dr. Sean Savitz, MD, on “Intravenous Cellular Therapies for Acute Ischemic Stroke”

Dr. Sean Savitz

Dr. Sean Savitz

A conversation with Sean Savitz, MD, Frank M. Yatsu M.D. Chair in Neurology, Institute for Stroke and Cerebrovascular Disease, The University of Texas Health Science Center at Houston, on stem cell therapies for acute ischemic stroke.

Interviewed by Mark R. Etherton, MD, PhD, Assistant in Neurology, Massachusetts General Hospital, Instructor, Harvard Medical School.

They will be discussing the paper “Intravenous Cellular Therapies for Acute Ischemic 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. Etherton: The data from MASTERS-1, as well as the animal studies, suggests a promising, immunomodulatory role for MAPCs in ischemic stroke, as well as for cells derived from other tissue sources. Can you speak to the advantages/disadvantages of MAPCs over other cell types?

Dr. Savitz: There are several advantages that make MAPCs appealing. One is that they have been studied extensively in pre-clinical animal models and now quite a bit in clinical trials, which has resulted in a significant amount of safety data obtained from these rigorously designed trials. So, in designing a therapy for stroke, I am of the opinion that it is important to choose a therapy based around animal studies and solid testing in early stage trials. We are encouraged by the fact that the clinical studies suggest MAPCs are safe in humans, and we already see signals suggesting that, if given in the right time window, the cells are effective to improve outcomes. In this respect, there are few if any other cell types that have gone this far on the continuum from animal studies to an impending phase 3 trial.

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.