Dr. Ronen Leker is the Director, Stroke Service and The Cerebrovascular Disease Center, Senior Neurologist, Department of Neurology, Hadassah Medical Organization. He is also the head of the academic department of Neurology, Neurosurgery and Rehabilitation Medicine at the Hadassah Hebrew University School of Medicine.

Dr. Leker is an expert on treatment and prevention of cerebrovascular disease including ischemic stroke and intracranial hemorrhage. He has been actively involved in clinical and basic stroke research for over 15 years both at Hadassah and at the National Institutes of Health (NIH) in Bethesda, MD where he served as a staff scientist at the Lab of Molecular Biology and worked on the use of neural stem cells as a novel therapy for stroke.

Dr. Leker established and directs the stroke center at Hadassah which includes the stroke intensive care unit, the stroke outpatient clinic and the Peritz and Chantal Scheinberg Cerebrovascular Research Laboratory. He has published over 140 research papers and serves on the editorial board of several international journals.

Dr. Leker graduated from the Hebrew University Hadassah Medical School in 1987 and completed his residency in Neurology at Hadassah Hospital.

Transcription:  Melanie Cole (Host): Did you know that stroke can affect anyone, even younger people. It can be so scary to think about. However, Hadassah Medical Center's pioneering researchers are leading the way in exploring a novel cutting-edge stem cell treatment to reverse the disability a stroke can leave in its wake. Today, we're speaking with Professor Ronen Leker on this episode of Hadassah On-Call.

Welcome. My guest today is Professor Ronen Leker. He's the director of Stroke Service and the Cerebrovascular Disease Center and a Senior Neurologist in the Department of Neurology at Hadassah Medical Organization. Welcome to the show Professor Leker. Tell us a little bit about yourself and how you came to Hadassah Medical Organization.

Professor Ronen Leker, MD, FAHA (Guest): Well, we're going back in history now. So, I started studying medicine in 1981 and that was in Jerusalem at Hebrew University Hadassah Medical Center and this is how I came to Jerusalem. And since 1981, I've been at Hadassah except for a short stint at the NIH in Bethesda, Maryland for three years between 2002 and 2005, all through medical school, residency, Army service and whatnot, I've been at Hadassah. So, Hadassah is basically my second home.

Host: Wow, that is a long time. Thank you so much for telling us about that. Now let's talk about stroke a little. Please define what a stroke is. Are there different types of them and is death more prevalent than other after effects that might happen like paralysis as a result of stroke?

Professor Leker: Well, there are two main types of stroke. The first type, the more common one is an ischemic stroke which happens when there is a disruption in the blood flow through the brain. It can be an occlusion of blood vessels outside the brain or inside the brain. But in any case, there is a reduction of blood flow to a particular part of the brain. And that part of the brain is then deprived of oxygen and nutrients and dies. And ischemic stroke comprises about 85-93% of all strokes.

The second major type of stroke is a hemorrhagic stroke wherein there is a tear in the wall of a blood vessel within the brain, so blood spills from the blood vessel into the brain tissue and damages the brain tissue. And this is responsible for between seven and 15% of all strokes depending on where you are on the globe.

As to your question, there are within ischemic stroke, there are numerous types of stroke. So stroke is basically a basket diagnosis. It is not a single disease. Stroke can occur as a result of an embolus that arises in the heart or a blood clot that forms in the heart and then just flows to the brain and occludes one of the arteries in the brain. It can be the result of an atherosclerotic disease in one of the arteries that leads to the brain and it can be the result of an occlusion in one of the small, very small, tiny arteries or very small arteries within the brain tissue itself. It can be the result of trauma. It can be many, many causes of stroke.

And as to your second question, no, death is definitely not the main result of stroke. Stroke mortality in ischemic stroke we are talking about anywhere between two and four percent of the patients. But many patients are left with significant disabilities in terms of motor impairment or sensory impairment or cognitive impairment, but they are not dead.

In hemorrhagic stroke, there is a mortality rate of about 30% to 40% which is much higher. But still, death is not the common pathway in stroke. Having said that, we should also remember that stroke is the between number two and number three killer in the world depending on which country you are in. So, it is a very common cause of death. But it's not - the main result of stroke is not death.

Each year, there are about 800,000 new cases of stroke in the US, around 18,000 in Israel and around a million or so in Europe. So, it's very prevalent. It is a very common disease.

Host: And I think we're hearing more about it too, Professor in that there's more awareness of like the acronym FAST and people are hearing about these symptoms and what to recognize. Tell us why you and physicians say time is brain. Tell us why time is so important when someone suffers a stroke.

Professor Leker: So, when you're having an occlusion of a large artery in the brain; it has been calculated by one of my colleagues Jeff Saver from UCLA, that for each minute you delay treatment, two million neurons die in your brain, which is a lot. So, time is definitely brain. And basically, once you deprive those brain cells--neurons--from getting their share of oxygen and nutrients, they die very quickly. So, we need to really move fast and open the occluded artery as fast as we can if we want to save brain tissue and minimize the damage and reduce mortality in that matter.

So, for ischemic stroke, we have two cardinal treatments that can do that. One is a medication that is given intravenously, and this is called TPA. That medication can be given to stroke patients up to four and a half hours from symptom onset. After that, if you give it, it increases the chances of having a brain hemorrhage. So, we cannot give it after that.

And the second option is when you have a large vessel occlusion; we can go in with a catheter and sort of pull the clot away and reopen the artery in a procedure called thrombectomy. This can be done up to seven and a half hours and recently, it has been shown that in some patients we can do this up to 24 hours and at Hadassah, we've been treating patients up to 48 hours even after stroke onset. But this is a very special group of patients that have good collateral circulation which means that they have arteries that circumvent the occluded part and sort of bypass it naturally and so the tissue is supplied, although not at a very good rate. Otherwise, they wouldn't have had the stroke at all but it's still getting some perfusion, some blood getting into the tissue which maintains it alive, but not doing well. But it gives us time to open the artery even longer than what we thought, what we were taught that we can treat which was up to seven and a half hours.

Host: What a great educator you are Professor, and thank you for explaining those treatments of mechanical thrombectomy and TPA and why it's so important that you see patients as quickly as possible. In the recent death of American actor Luke Perry from a stroke at what seems to be a younger age--the man was in his young 50s--is there a correlation between someone's age and having a stroke? Are there certain risk factors that would change for a younger person versus an older person?

Professor Leker: Certainly. Yes. But we need to remember that 25% of all strokes are in patients that are younger than 60. And anyone at any age can have a stroke even children can have it. So, most of our patients around 50% of our patients are between the ages of 60 and 80, 25% are over the age of 80 and 25% are under the age of 60. But in younger patients, in patients in that age group of 48, 50 and lower, we need to think of other causes of stroke, other than the usual heart disease, atherosclerosis which is also common in these patients, but we need to think of other stroke mechanisms as well, such as hypercoagulability which can be genetic, drug use, some illicit drugs like amphetamines and cocaine have been associated with an increased risk of stroke. Even weed -- marijuana has been associated with stroke. And also traumatic dissection of an artery like people that are getting hit in the neck area during sports or during a car accident can cause a tear in the wall of an artery which causes a clot to form there and part of that clot can embolize, can move with the blood stream upwards towards the brain and can occlude an artery in there.

Also in hemorrhagic stroke, there are vascular malformations which can be genetic or acquired and, in these malformations, which means that the blood vessels are not the normal variety, they leak more and they can burst, it can have an aneurysm and have a subarachnoid hemorrhage while you're exercising for instance. So, yeah, I mean in younger people, we need to think outside the box as you would normally think.

Host: I think that's what's so scary for people, is how would we know if we are a younger person, and you've mentioned many of these risk factors. Would you advise people to talk with their primary care provider to see if they are at risk? If they are, is there any way to tell?

Professor Leker: For sure, yeah. I think that the main traditional risk factors are high blood pressure, high cholesterol, diabetes, sedentary lifestyle, so you need to take care of yourself. That's basically the usual advice we give people. Stop smoking, exercise, maintain a Mediterranean type of diet which is a diet rich in olive oil instead of vegetable oil, fish instead of red meat and vegetables and fruit and with high cellulose content. Exercise at least 30 minutes per day and keep your cholesterol low, keep your blood pressure low. Those are the modifiable risk factors.

Of course, there are other risk factors for stroke that are non-modifiable. For instance, you cannot change your genetic background. So, if you have a family, a rich family history of stroke, your parents had a stroke, your brother had a stroke, your sister had a stroke, you're at increased risk. But if you take care of your modifiable risk factors, that is, you stop smoking and you start exercising and you keep an appropriate weight and you lower your blood pressure and you take your cholesterol lowering medications -- then you will lower your chances of having a stroke.

Host: And that's always really great advice Professor, and I thank you for kind of reiterating that because it's so important that people do hear about those modifiable risk factors. Tell us about some of the exciting cutting-edge treatments including using stem cells that you're developing at the Hadassah Medical Organization that could reverse some of the disability that could come in the wake of a stroke.

Professor Leker: Right, well, so, we've discussed earlier the impact of thrombectomy and of TPA. But these treatments can only be given very early during the course of the disease and then as I mentioned, some patients are still left with significant disabilities whether motor, sensory, cognitive and then we don't have a way of repairing that. So, stem cells represent a new and exciting way to try and help these patients once they have gone through the initial treatment, if they got it, if they got to the hospital in time or even if they didn't get to the hospital in time; we can still help them maybe sort of recover. It's part of the recovery process. So, stem cells are cells that reside in the brain and neural stem cells can transform into adult neurons and support cells which are called glial and basically, repopulate the brain anew.

Right now there are two main strategies of using stem cells for stroke. The first is to use other cells, not cells from the brain itself, but cells from bone marrow or cells from bone or cells from dental pulp and all these strategies and modified embryonic stem cells. So, people take these cells, grow them in a dish and then transplant them to the brain by various methods after the stroke. So, this is one strategy. And this has been in clinical studies. So far results seem to be exciting, but it's not yet there. I mean we're not there yet in terms of everyday practice.

The other strategy which my lab is working on is to take the neural stem cells which reside in our brain. They are residents there in your brain, in my brain, in everybody's brain and the point is that when you have a stroke, and you are kind of older; these cells do not respond well, and we are working on methods to stimulate these cells and manipulate them in a way that they will transform into neurons and will be able to maybe replace the cells that have basically died during the stroke.

This is a complicated process and we are at the stage of doing animal studies. We're not yet in the stage of doing clinical studies in humans. There are a lot of risks associated with this kind of treatment. We were able for instance to multiply the number of these cells by thousands and hundreds of thousands, but the problem is that some of these cells can turn into malignant brain cells. So, we don't want them to save a patient from stroke but then cause them a brain cancer. So, we are working on ways to neutralize these malignant transformation of these stem cells and to be able to monitor them more carefully so we will be left with a safe way of treating patients.

So, this is exciting. There's still a very long way to go. And we need a lot of funds to do that which is challenging as you may know. But we're working on that and hopefully we'll have a treatment within a few years.

Host: Well I'm sure with people like you on the case, we certainly will. How exciting, really. What a fascinating field that you are in Professor. As we wrap up, where else do you see the field of stroke care going from here? And how does what you're doing in Israel translate to the world model of care?

Professor Leker: Well, we're trying to be at the forefront of stroke care in the world. We are participating in studies. We are among the first – Hadassah is among the first centers in the world that used thrombectomy with the newer thrombectomy devices. So, we are publishing a lot and we're doing a lot of research.

I think that you'll see more and more thrombectomy devices that will enable treating patients in a longer therapeutic window and in smaller blood vessels. So, right now, this thrombectomy field is sort of limited to larger blood vessels say within the brain. But I'm sure that with time we'll be able to penetrate into smaller and smaller blood vessels and retrieve clots from there as well. So, this is one way that the field is going.

The other way, is maybe to extend the time window for use of drugs that can be given systemically, intravenously and break the clot, like TPA. As I mentioned earlier, TPA can be given up to four and a half hours from symptom onset. But with maybe developing new drugs that can be given at an extended time window without the risk of having a hemorrhage; we'll be able to treat patients who live in more rural areas where thrombectomy is not as accessible and this is pertinent to the states, I'm sure. Or Australia or New Zealand or places where you can live in a remote area which might have a primary care hospital but no endovascular neurosurgeons that can actually do the thrombectomy.

So, we are working on drugs that can be given at an extended time window so that patients can benefit from that. And of course cell therapy which we just mentioned, with stem cells be it like from neural stem cells like the angle that we are attacking or mesenchymal stem cells or bone marrow stem cells or whatever the other people are working on; it's going to be interesting.

Host: It's wonderful information Professor. It's really cool to hear as somebody listening to you describe these research studies, it's absolutely fascinating. Thank you so much again for joining us today, for sharing your expertise because we're hearing more and more in the media about stroke and you've really educated us today. Thank you again for being with us.

This is Hadassah On-Call, New Frontiers in Medicine brought to you by Hadassah, the Women's Zionist Organization of America. The largest Jewish Women's organization in America, Hadassah enhances the health of people worldwide through medical education, care and research innovations at the Hadassah Medical Organization. For more information on the latest advances in medicine please visit www.hadassh.org, and to hear more episodes in this podcast series please visit www.hadassah.org/podcasts, that's www.hadassah.org/podcasts. There are some wonderful podcasts on there for you to listen to and share with your friends. This is Melanie Cole. Thanks so much for tuning in.

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