Stroke — Dr. Winstein's Recovery Research Kaiser Permanete ad

The word dates from the late 16th century and originally referred to a sudden lapse in consciousness, believed to come from the “stroke of God’s hand.” That sounds pretty tame compared to how we think of strokes today. As you may know, a stroke takes many forms, including blood hemorrhaging into brain tissue, and ruptured aneurysms.

Strokes affect 700,000 people each year in the US. In the end, most of them are left with debilitating deficits. This has spurred medical scientists to seek new ways to improve the brain’s ability to bounce back from such a devastating blow. Recent advances suggest that after a stroke, there’s potential to heal sick neurons in the brain, which led researchers at Northstar Neuroscience, Inc. to test this theory on rats. Strokes were induced in the lab anminals, then scientists placed low-voltage electrodes on the surface of the brain that was still functioning. They hoped that this extra stimulation, combined with conventional therapy, would improve recovery. Sure enough, it seemed to work. After several more experiments by different scientists, and rigorous review by regulatory agencies, Northstar provided funding for several university research centers across the country to execute a trial on humans.

To learn more about this project, Chet Cooper, ABILITY Magazine’s editor-in-chief, and Dr. E. Thomas Chappell, ABILITY’s health editor, inched through infamous LA traffic to visit Dr. Carolee Winstein, professor of biokinesiology and physical therapy at the University of Southern California’s School of Medicine. They found her seated in her cozy, but well-organized office.

Chet Cooper: Let’s talk about the Northstar studies.

Dr. Carolee Winstein: The exciting aspect of these studies is that they use technology in conjunction with highly-focused physical therapy in a way that helps patients recover better after a stroke. A stimulator is placed on the damaged area of the brain to make those neurons a little more active, and help them “reorganize” in response to the movement that the patient is going through when they’re in therapy. So the electrode is turned on only while they’re getting therapy.

Cooper: Is this an implanted electrode?

Winstein: Yes. Actually, a small area of the skull is taken off, and the electrode is placed right on the dura, which is that tough membrane that covers the brain, and then the skull is put back on. A wire runs under the scalp to an electric generator implanted under the skin on the patient’s chest, much like a pacemaker for the heart. A magnetic “wand” can then be held over the patient’s skin above the implanted device to turn it on and off.

Cooper: So do you map out the brain to determine where the device is best placed?

Winstein: What’s done, which is really innovative, is that the patient undergoes a functional magnetic resonance scan (fMRI). So we see the area of the brain that “lights up” on the scan. In other words, the area that’s active when the patient is trying to move an affected limb in whatever way they’re able to move it after the stroke. And then that area is used to decide where the electrode goes. So you’re really optimizing, not just putting the electrodes where you think they should be. You’re putting it where the neurons may be sick but not dead, according to the fMRI. The idea being that some neurons have the capability to return to normal.

Cooper: What if the patient has absolutely no movement in that particular hand or arm?

Winstein: Then they’re not a candidate for this type of treatment. There’s no miracle here. Basically, if there is some connection between the brain and the hand, as evidenced by the fact that they have some movement, then that serves as a substrate for the stimulator.

Dr. E. Thomas Chappell: And this is being done in small groups of patients now?

Winstein: Yes, by a neurosurgeon right here at USC. But there are 21 medical institutions across the U.S. participating in the study.

Chappell: Your neurosurgeon here probably specializes in epilepsy, right? Those are the surgeons that are more used to putting in these types of devices.

Winstein: Right, and he does some of the deep-brain stimulation surgery as well. What’s interesting from a neurosurgery perspective is that to him, this is totally a piece of cake. I look at this and I say, “God, they’re opening up the skull!”

Chappell: Not many people realize that neurosurgeons open up patients’ skulls every day, and often to do much more involved procedures than place electrodes, which doesn’t mean that placing electrodes doesn’t have its risks, such as infection or bleeding.
Let’s talk more about what you learned from the lab animals.

Winstein: There were rat and primate models. It was actually in that work that they determined that the combination of physical therapy plus electrode stimulation is better than just physical therapy alone.

Chappell: So researchers have some way of causing the experimental animals to have a stroke and then they provide them some type of physical activity?

Winstein: Yes. Currently, there’s a lot of animal research done using skills training, such as picking food pellets out of little cups and other fine-motor skills. For instance, they use what’s called a Kluver Board, for example, which has holes that start out big and get progressively smaller. Scientists train the experimental animals to pluck banana pellets out of progressively smaller, and thus more difficult-to-access holes. That requires individual finger movement. So the parallels between the animal model and what we do in therapy for humans get closer and closer. It’s really exciting.

Chappell: And how does that translate to what they’ve done with humans.

Winstein: They did two small-scale human studies. I think the first one involved only four patients, and the second one maybe 12. I think eight had the surgery and four didn’t in that study. The four that didn’t served as the control group so that a comparison could be made to see if the people that got the electrode stimulation really faired better. All subjects got physical therapy, but only the eight got the electrode implanted. So the question is whether the risk of having this kind of surgery would actually benefit a stroke patient more than just therapy alone, because obviously that’s going to have to be proven.

Cooper: And the Northstar study has how many subjects?

Winstein: The one that we’re doing right now, which is the pivotal trial, has something like 180 subjects.

Chappell: Throughout the 21 centers?

Winstein: Yes 21 centers. So far, they’re doing pretty well. Northwestern University is in the lead now, I think they’ve randomized on the order of 30-some. We’re up to I think 13 or 14 patients that we’ve randomized here at USC. We’ve been doing this now since we got IRB approval a year ago January.

Chappell: And how long has the study been underway?

Winstein: Well, I think they’ve been recruiting patients for the study since 2005.

Chappell: Has there been an interim analysis at all?

Winstein: Not that I know of. Everyone involved in the study is blinded to the ongoing results, of course.

Chappell: And the data gets sent to a central data processor?

Winstein: Right. Exactly.

Cooper: Why do you think they are putting press releases out now, while it’s still in this stage?

Winstein: I think it’s probably just to let the community know that this is coming down the pike. I think Northstar has carved out a somewhat unique niche. They’re also looking to have a small study going to treat aphasia, for those who have speech deficits after a stroke. There’s going to be a larger-scale study starting up in Germany, I think. Northstar has really done their homework. and they’re collaborating with a number of basic scientists to understand the frequency and strength of the electrical stimulus.

Cooper: How would they handle the therapy for aphasia?

Winstein: Well, I’ll tell you what’s really interesting about the aphasia study: it started because they had some anecdotal data from earlier studies. Some patients with both paralysis in the right hand and difficulty with speech would get both motor and speech recovery therapies. So they thought that it might be worthwhile to specifically target the speech area. If you think about it, you’re facilitating the connection. You have a damaged area of the brain that is not working well after the stroke. The question is, how can we get the connections that were lost back? And we now understand that the brain is really much more plastic (capable of changing at the cellular level) than we’ve given it credit for. It’s not this static thing that you take a chunk out and it’s gone. It’s constantly reorganizing. That’s how we learn new things.

So they’re thinking about that from the standpoint of what might facilitate the development of new connections in the brain and then coupling it to meaningful physical activity. So for recovery of speech, a patient would practice verbal tasks while the electrode stimulates their brain at a low level. It is just enough to get the neurons “buzzing” so they are more likely to make the new connections necessary for recovery of function. Though it seems to help, no one knows exactly why. It’s all theory at this point.

Chappell: The challenge here is to have enough electrical stimulation, but not so much that you cause seizures.

Winstein: Right. I think of it as just sort of slightly raising the electrical baseline for neurons so they’re more likely to “fire.” But they’re actually firing in response to the functional demands that are being placed on them in the therapy. You’re sort of raising the capability of “sick” neurons to work, and you’re influencing how they work through physical and speech therapies. That is why the combination of the electrical stimulation and the physical therapy is so important. It’s not a passive, “slap on an electrode, I’m going to get better” kind of thing. It’s really putting the two together, which is the exciting part..
... continued in ABILITY Magazine

ABILITY Magazine
Articles in the Frankenstein issue; Emme Aronson—Couples Fighting Depression; Car Wars—May the Force be Green and a Q&A with Toyota; Humor Therapy; Pet Peeves; All the World's a Stage, But How Do I Get a Ticket to the Show—Disability Legal Rights Center; Iraq Vets—Healing on the Slopes; Virginia Tech—Lessions to be Learned; Chop Chop—Try a Raw Food Diet; ABILITY's Crossword Puzzle; Events and Conferences...subscribe

Excerpts from the Frankenstein issue:

Earl Bakken Interview

Road to Qatar — Allen Ruckers Reports

Stroke — Dr. Winstein's Recovery Research

Augie Nieto's — Quest to Coquer ALS

Chop Chop — Try a Raw Food Diet

Humor Therapy — Pet Peeves

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