The word dates
from the late 16th century and originally referred to a sudden lapse in
consciousness, believed to come from the stroke of Gods 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 brains ability to bounce back from
such a devastating blow. Recent advances suggest that after a stroke,
theres 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 Magazines
editor-in-chief, and Dr. E. Thomas Chappell, ABILITYs health editor,
inched through infamous LA traffic to visit Dr. Carolee Winstein, professor
of biokinesiology and physical therapy at the University of Southern Californias
School of Medicine. They found her seated in her cozy, but well-organized
Chet Cooper: Lets 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 theyre in therapy. So the
electrode is turned on only while theyre 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 patients
chest, much like a pacemaker for the heart. A magnetic wand
can then be held over the patients 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
Winstein: Whats 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 thats active when the patient is trying to move an affected
limb in whatever way theyre able to move it after the stroke. And
then that area is used to decide where the electrode goes. So youre
really optimizing, not just putting the electrodes where you think they
should be. Youre 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 theyre not a candidate for this type of treatment.
Theres 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
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
Winstein: Right, and he does some of the deep-brain stimulation surgery
as well. Whats interesting from a neurosurgery perspective is that
to him, this is totally a piece of cake. I look at this and I say, God,
theyre 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 doesnt mean that placing electrodes doesnt
have its risks, such as infection or bleeding.
Lets 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, theres 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 whats 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.
Its really exciting.
Chappell: And how does that translate to what theyve 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 didnt in that study. The four that didnt
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 thats going to have to be proven.
Cooper: And the Northstar study has how many subjects?
Winstein: The one that were doing right now, which is the pivotal
trial, has something like 180 subjects.
Chappell: Throughout the 21 centers?
Winstein: Yes 21 centers. So far, theyre doing pretty well. Northwestern
University is in the lead now, I think theyve randomized on the
order of 30-some. Were up to I think 13 or 14 patients that weve
randomized here at USC. Weve 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 theyve 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
its still in this stage?
Winstein: I think its probably just to let the community know that
this is coming down the pike. I think Northstar has carved out a somewhat
unique niche. Theyre also looking to have a small study going to
treat aphasia, for those who have speech deficits after a stroke. Theres
going to be a larger-scale study starting up in Germany, I think. Northstar
has really done their homework. and theyre 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, Ill tell you whats 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, youre 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 weve given it credit
for. Its not this static thing that you take a chunk out and its
gone. Its constantly reorganizing. Thats how we learn new
So theyre 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. Its
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 theyre more likely to fire.
But theyre actually firing in response to the functional demands
that are being placed on them in the therapy. Youre sort of raising
the capability of sick neurons to work, and youre 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.
Its not a passive, slap on an electrode, Im going to
get better kind of thing. Its really putting the two together,
which is the exciting part.. ...
continued in ABILITY Magazine
Articles in the Frankenstein issue; Emme AronsonCouples
Fighting Depression; Car WarsMay the Force be Green and a Q&A
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