March 23, 2016

Recovering from Stroke

The Human Brain: Episode #7

According to the American Stroke Association, on average, someone in the United States experiences a stroke every 40 seconds. It's the leading cause of adult disability in the United States. Catherine Lang, director of the Neurorehabilitation Research Laboratory and professor of physical therapy, neurology, and occupational therapy at the School of Medicine at Washington University in St. Louis, wants to improve the ways that doctors and physical therapists help people recover from stroke. In this week's podcast, she shares some dramatic findings from one ongoing experiment.

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Full Transcript

Claire Navarro: Hello, and thank you for listening to Hold That Thought. I’m Claire Navarro. You probably know someone who has visited a physical therapist perhaps after an accident or an injury. Maybe you yourself have seen a physical therapist somewhere down the line. Physical therapists, like Catherine Lang, are trained to help people who have problem with movement, whether it’s getting up the stairs or lifting a finger. But in this line of work, Lang focuses on more than just a person’s muscles.

Catherine Lang: All of our ability to move—yes, you have to have a skeleton, and you have to have muscles—but its really the nervous system, and in large part the brain, that lets us make the incredibly beautiful and complex movements that humans can make. Think of elite gymnasts or a violin virtuoso; I mean, those are trained movements that are highly skilled, and it is really the person’s brain that is the right limiting factor often more times than some of the muscles.

CN: Dr. Lang is a professor of neurology in addition to being a professor of physical therapy and occupational therapy at Washington University in St. Louis’s School of Medicine. There she also directs the Neurorehabilitation Research Laboratory. Shortly after getting her PhD, she did research on how specific areas of the brain control tiny, precise finger movements. From there, her fascination with the human body, and in particular the brain, led her to turn her attention to what some people call “brain attacks”. That is stroke.

CL: A stroke is simply lack of blood-supply to the brain. The brain has many different areas in it, so the problems that you have as an individual with your stroke depend on where that stroke is in your brain. If your stroke effects the areas that control your movements, then you might have difficulty walking, you might not be able to move you hand, which then leads to difficulty with doing things like getting dressed and taking care of yourself and feeding.

CN: A stroke that occurs in a different part of the brain might lead to a different kind of problem, like not being able to speak or be understood. Whatever the specific symptoms, a lot of patients who have had a stroke end up working with physical therapists.

CL: An interesting thing about stroke is about 80% of people end up with motor problems initially, and then about 50% of people end up with persistent motor problems. There is a portion of people who get completely better and are normal, but there are a lot of people with deficits that last for a very long time.

CN: Lasting problems often mean long-term therapy at more than one hospital or facility. To help keep teams of doctors and therapists on the same page, Lang helped found a group called The Brain Recovery Core. The group shares data and works on individualized treatments to help patients on their long road to recovery. On the research side, Lang looks at questions like, “What dosage of therapy is best for any one patient?” Here we are thinking about dose as a certain number of movements instead of a certain amount of medication. And in addition to looking at existing therapies, Lang is also interested in how new treatments can help these patients. One in particular is both promising and really surprising. It starts with a phenomenon.

CL: There is this phenomenon called ischemic conditioning that has been around for a number of years.

CN: That’s ischemic conditioning. Ischemic conditioning is not an exercise or a movement. It is what happens when you temporarily cut off the blood supply to a certain part of your body. We’re talking about limiting blood flow to an arm or a leg, not something dramatic like cutting off blood supply to the brain and causing a stroke. Over the years scientists have done studies with animals and ischemic conditioning. And it’s been shown to have some pretty remarkable results.

CL: This has been shown to be cardio-protective, meaning if you have a heart attack and you have had this ischemic conditioning, then your heart attack is smaller and you do better. There is some emerging data is animal models that it is neuro-protective, so if you do this conditioning in a rodent model and then you give these rats a stoke, their stroke is smaller and they do better.

CN: So for both heart attack and stroke – animals that had the conditioning did better. What’s going on here? How could cutting off blood supply make an animal more resistant to a heart attack? Or a stroke? In large part, the answer to that question is still a mystery.

CL: What it does is causes your tissues to secrete some “magic factors,” and I’m putting these in quotes because we don’t really know what they are. But there is something secreted in the blood that confers this protection. They know this because they have actually taken blood from one animal who has had the ischemic conditioning and provided a transfusion to another animal who hasn’t had it.

CN: And, you guessed it, the animal with the transfusion also did better. Whatever this magic sauce caused by ischemic conditioning is, it stays in the blood. So far we’ve been talking about rodents. But what about humans? Lang wants to know whether ischemic conditioning might be able to help patients who already have had a stroke get better. So, she’s putting it to the test. In her lab, she gives people ischemic conditioning using a simple blood pressure cuff.

CL: So I can put a blood pressure cuff on your arm, and I inflate it to a certain amount over your blood pressure, which essentially cuts off the blood supply to your arm.

CN: This is a very controlled process that lasts a short amount of time, so there’s no danger of damaging the tissue in the person’s arm. In the experiment, all the participants put on the blood pressure cuff. Some people get the ischemic conditioning; others don’t. The people whose cuffs aren’t inflated as much are getting what Lang calls “sham conditioning.” After that step, the participant heads over to a playground. Well not really, but something sort of like it.

CL: Our target task right now is a balance board. You are standing in the middle of a seesaw, and you are trying to keep the seesaw level. What we do is we test you on that—and you are pretty bad at it when you start. But we give you experience, or training exposure to it over and over and over again, and we see how you do. Most people show these nice learning curves where they get progressively better over time.

CN: All the participants improved the more they practiced, but some people could learn much faster.

CL: The people that receive the ischemic conditioning learn about 70% more than the people who receive sham conditioning.

CN: That’s 70 percent more. If that seems like a dramatic result, that’s because it is.

CL: In the years that I’ve been doing research, I’ve never seen an effect that is this strong and this consistent. It seems that every single person that gets the ischemic conditioning does a lot better than every single person that gets the sham.

CN: This could be a really exciting development for people who have suffered a stroke. If ischemic conditioning helps people learn how to balance on a board, it’s possible that it could also help people learn other motor tasks – like how to walk again after having a stroke. The next big question is figuring out the ingredients of the secret sauce and how to best use it to help real people with motor problems.

CL: Part of this secret sauce might be proteins that enhance nerve growth and help you establish stronger connections between the neurons that you need to do this particular task. Now we are going to investigate lots of questions surrounding that, like what different kinds of tasks might people learn on. We have targeted those tasks to the kind of training and learning experiences that people have during stroke rehabilitation. We are also very interested in who it might work on. There are some animal studies that suggest that rats that have had their ovaries removed don’t show as much of a response, and of course, the human equivalent of that is post-menopausal women. There are some other suggestions that some different conditions that might occur in people with stroke might not make it as effective as we would hope, so we are explicitly going to test all those things. The goal would be to have a sample of people with stroke to test it on.

CN: In short, there are plenty of questions to keep Dr. Lang and her colleagues busy for years to come. And she sees that as simply the nature of working on something as complex as the human brain.

CL: It’s kind of like, you learn something, and when you learn something, instead of answering the question you set out to learn, now you have a partial answer and five new questions. It’s really quite fascinating in that way. I think we are going to be—we meaning the volume of population of neuroscientists and people interested in the brain—are going to be studying this for decades to come.

CN: Many thanks to Catherine Lang for joining Hold That Thought. For many more ideas to explore, including more from our series on the Human Brain, please visit us at holdthatthought.wustl.edu. You can also find Hold That Thought on Facebook or Twitter or subscribe to our weekly podcasts on iTunes, Stitcher, PRX, and SoundCloud. Thank you for listening.