University of Cincinnati neurologist Pooja Khatri, MD and neuroradiologist Achala Vagal, MD talk about a new way to treat strokes.
Interview conducted by Ivanhoe Broadcast News in 2022.
What’s happening to the body and the brain at the time of the stroke?
KHATRI: A stroke is when there’s disruption of blood flow to the brain such that an area of the brain just suddenly stops working. It can be either because the blood flow got blocked or because the blood vessel ruptured and the blood spilled into the brain.
When you have that an emergency, what’s the important thing for people to remember?
KHATRI: There has been such a sea change in our treatments. The faster you get to the emergency department the better. If you have any sudden symptoms, you can’t explain and we tell people to remember the word FAST, F for face, A for arm, S for speech and T for time. Any symptoms you can explain better off making a mistake, but just come early because we can give you medicines to dissolve the clot that’s blocking the blood flow or potentially pull it out with a catheter.
After a stroke, what are the potential? And every patient is different, but what are the potential impacts? Especially if people don’t get treatment right away.
KHATRI: One of the common things that can happen to people is weakness. Usually it’s on one side of the body or the other. You might have numbness on one side of the body or the other. Trouble speaking, producing speech, understanding speech, trouble seeing on one side of the visual field or the other. Those are some examples of major symptoms that people can have.
Can people recover from stroke?
KHATRI: Absolutely. In fact, there’s often this misconception that what’s happened in those first 24 48 hours is the whole story. While we do have treatments that can completely reverse stroke in the 24 to 48 hours, it is amazing what the brain does in terms of rewiring, getting other areas of the brain to help out. We know that we see recovery oftentimes up to months and even up to years later when we work with our patients. Really the big thing is though that we can’t predict who will recover and who won’t recover. We have to just give it time knowing that a lot of people have at least some improvement, but only time will tell how much.
Even after all this time with research, you still can’t predict whether people will get the function back yet?
KHATRI: Absolutely, it is actually, it’s a great point. It’s such a bread and butter question that needs to be answered. It would help us do better research and it would help us take better care of our patients, plan what they’re going to need to help them recover, what support they need at home. Many reasons it would be really useful to give that prediction. We’re right on the cusps and we’re excited that we get to do this study to just solidify our understanding on this.
I want to talk to you about the study. What ultimately is the goal?
KHATRI: The goal of the study is basically there are two major biomarkers and I can tell you about those. Our preliminary studies suggest that they’re very good at predicting who will recover their strength, but specifically in their arm. The goal of the study is to see if we take these biomarkers and we use them nationally where you’ve got 35 sites across the country that are learning to use these biomarkers. Will we be able to predict with a high degree of accuracy whether that patient is going to get improved strength? Whether they’re going to be able to use that arm and how that’s going to affect their overall function and quality of life.
Can you talk about those biomarkers?
KHATRI: Yeah. There are two main biomarkers. One’s called transcranial magnetic stimulation or TMS. That one is measuring whether there’s still inherent function left. In other words, we’re zapping one side of the brain. This side of the brain controls this arm, for example, and we’re seeing if the hand moves and we’re actually measuring the impulse of the muscle. To see if we’re even seeing tiny muscle movements that tell us that the brain is successfully talking to the hand.
And the second?
KHATRI: Then the second one is structural. We say functional versus structural. The second one is MRI lesion load. The idea there is many people have heard of this. You get into an MRI, we take a picture of the brain. There’s a lot of untapped information and what we’re really excited about what this study is it’s just routine clinical imaging that are already doing that we can analyze and we can say what percentage of say the motor tract in this case we’re starting the motor tract is actually damaged. Our studies suggests that the percentage of damage will predict the degree of recovery. If there’s some intact motor fibers, we’re expecting some recovery and those two hand in hand may be the perfect combo. That’s what we’ll figure out for sure.
When you have that information, what can you do with it? What can other health providers do with that information?
KHATRI: It’s helpful contexts to know that there have been over one thousand randomized trials in recovery and almost all have been basically negative. We think it’s because there’s so much noise in the system even before we’re trying to do this recovery intervention it’s a mixed bag of apples and oranges who’s going to stay weak, who’s going to improve, who’s going to completely get back to normal. If you could sit those people out, you could do better and more efficient studies and then you could target your therapies for the right groups. We’re expecting that we’re going to make research go faster for stroke recovery with these results.
Talk to me a little bit about the trial. What is it called? How many centers and over what period of time?
KHATRI: It’s called verify and it’s a 657 patient study across 35 centers in the United States. It’s a wonderful partnership I should note between the more emergent care doctors, the ones you take care of the patient within the first few hours and the people who take care of the patients in the recovery stage. We’re all working together on this, which I had some side benefits that are measurable. I should say it’s not just doctors. The beauty of this study is it’s our research coordinators or physical therapists or occupational therapists all working together on this question.
Over what period of time when you look at that data?
KHATRI: Over five years. We just finished our first year where we got everybody trained up and we’re starting to enroll patients. We’re at an exciting time and things are really rolling and sometimes trials struggle. I’m happy to say that we’re exactly on target right now for recruitment.
If there’s a takeaway that you’d want our viewers to know down the road once you get your data back five years from now, how do you anticipate this will impact your field, impact stroke and recovery?
KHATRI: Beyond the long view of hopefully getting better therapy is what I hope will happen is at the bedside it’ll become more common to do this and then be able to talk to a patient and their family and say, you know, their odds are pretty good that you’re going to get this arm strength back. Really work at it or it’s not looking good and what social support do you have? How can we help you succeed? What are other ways we can help you do the activities that are important to you? Start planning more proactively than just saying how it plays out.
We’re talking about stroke. I wanted to ask you a little bit more coming from the imaging side of it. What is it that you and your colleagues are looking at? How are you going about gathering the information that may help you with this study?
VAGAL: Yes. In this study, we are going to do an MRI, which is the routine MRI. Usually patients many times when they come into the emergency department, they can get a CT or an MRI. For the purposes of this study, we are doing a routine MRI and in the MRI there are multiple sequences. What we are really interested in understanding, where is the stroke or that dead brain tissue. Then looking at the tracts, there are certain important tracts that we are looking at and seeing what that infarct or that stroke lesion is doing to the tracks how much overlap is there? What is the percentage of that tract that is basically taken up by that stroke lesion and that helps us in predicting recovery? On the MRI, there is one part where we’re just gathering the data when the patient is in the scanner usually takes 30 to 40 minutes. Then we do some additional post-processing and computerized algorithms to use to see what is the overlap of that lesion and the tract.
Is there a correlation between that overlap and the amount of mobility that a patient may or may not get that?
VAGAL: Absolutely. I think the mobility of the tract is- the mobility of the arm is based on how intact that tract is in the brain. If the stroke lesion is disrupting the tract or is very much overlap, almost sometimes to 100 percent, then chances are that there will be very reduced or almost no mobility after the stroke.
Why is it so important to know how much of an overlap there is? Why is that important?
VAGAL: I think the degree of overlap is sometimes more important than how large the lesion is. If you are looking, particularly in this study, we’re looking at the upper arm mobility and the tract which controls that. That overlap sometimes going to be more critical than it might be a big lesion, but if only small part of that tract is involved, then the chances of a better recovery.
The MRI you are mentioning to me, the imaging is one part of the study. Can you talk to me about the multiple parts and partners that are involved in this?
Vagal: Yes. This study has multiple leaders too, and we’re very proud of the leadership team. One is Dr. Pooja Khatri, who’s a neurologist at University of Cincinnati. I’m a neuroradiologist and our other two leaders are Dr. Cathy Stinear, who’s from the University of Auckland in New Zealand. She’s an applied clinical neuroscientist. Then we have Dr. Steve Cramer from UCLA and he’s a neurologist but focuses on recovery. The leadership team is exactly what we are seeing in the rest of the 30 plus sites around the country. Both the acute people who are taking care of, when the patient comes, and all the way to recovery.
The importance of having so many sites and so many patients are large pool of data. Can you speak to that just a little bit?
VAGAL: Yes. Number one, it helps in generalizability of the study. It’s always good to do a multicenter such that we can have different adverse pool of the patients so that when the results come out, we are confident that this is going to be applicable to a larger number of more diverse patients. That’s one of the goals of the study.
What is your partner, Dr. Cathy Stinear doing with the TMS?
VAGAL: Dr. Cathy Stinear has been one of the pioneers of the TMS technique and one of her works that she has shown how important the stimulation in the TMS and what we call the MEP, which are the evoked potentials. I think that work is being so critical. We are trying to validate that biomarker that she’s been working for.
What would you want people to know about what you and your colleagues are working on right now?
VAGAL: I think what we want them to know is that the boat structure and function are important when it comes to predicting which patients will recover after a stroke. We want them to know that there is a lot of science being done. Then there are a lot of dedicated people all around the country and the world who are working so that one day every stroke is reversed.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
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