|
Research Highlights
At Baltimore VA, stroke recovery studied from many angles
October 23, 2008
Reggae music pulses through the large, brightly lit gym in
the basement of the Baltimore VA Medical Center. About
eight men and women, some holding canes, slowly make their
way around the green and yellow oval track. Each step seems to
demand effort and concentration for the members of the group,
but they are making steady progress toward their goal: recovery
from stroke.
The Stroke Exercise Club meets three afternoons a week as part
of a study on whether group exercise, reinforced with a homebased
regimen, improves balance, fitness, walking ability and
quality of life for stroke survivors. Exercise physiologist Jeff
Beans—who says the eclectic mix of music for the classes ranges
from Bob Marley to Frank Sinatra—believes the group atmosphere
is "paramount" in helping older people
regain function. Neurologist Richard Macko,
MD, agrees: "It makes it fun, and the social
reinforcement appears to sustain exercise
behaviors in the elderly."
Macko heads the Maryland Exercise and
Robotics Center of Excellence. The VA-funded
program, which aims to improve
fitness and movement and reduce disability
for people affected by neurological
illnesses, is a hub for stroke rehabilitation
and research at the Baltimore VA and its
academic affiliate, the University of
Maryland School of Medicine. The program
works hand in hand with VA’s Geriatric
Research, Education and Clinical Center
(GRECC), directed by Andrew Goldberg,
MD. The Baltimore GRECC is one of 20
such programs that VA supports nationwide.
Stroke studies link findings
from lab, clinic, gym
Group exercise is one of the hottest
topics under investigation by Macko and
colleagues. Launched in 2003 through a
collaboration with Italian stroke experts, the
VA research effort examining this question
will soon expand through partnerships with
local senior centers and Veterans of Foreign
Wars posts.
Other stroke researchers at the Baltimore
VA, with funding from VA, the National
Institutes of Health and other sources, are
looking at issues such as the use of robots
for stroke therapy, the effects of different
types of exercise on walking ability, and the
role of strength training in stroke recovery.
Beyond the clinic and gym, stroke studies at
the Baltimore VA also involve lab analyses
of the genes and proteins involved in the
disease. Biopsies of muscle tissue, for
example, have pointed to a chemical called
TNF-alpha as a possible cause of the
wasting that occurs on the side of the body
affected by stroke. "The damage of stroke is
not all in the head—it's in the muscle also,"
points out Macko. Muscle tissue from a
patient's affected side has up to three times
more TNF-alpha than non-affected tissue.
TNF-alpha not only shrinks muscles—it
also interferes with the action of insulin.
That may explain the results of a 2006
Baltimore VA study, led by Macko’s
colleague Frederick Ivey, PhD, showing that
more than three-quarters of stroke patients
with paralysis on one side of their body
have diabetes or a precursor condition
called impaired glucose tolerance. "This is
more than double the expected rates,"
explains Macko. "We believe it's because of
these secondary biological changes in the
muscle and the body composition that occur
after a stroke."
Interestingly, diabetes is one of several
diseases—including AIDS and cancer—that
involve abnormally high levels of TNFalpha
in muscle tissue. "This is an
ubiquitous molecular signal that appears to
be related to these metabolic wasting
syndromes, including diabetes. And now we
find it in stroke. It’s a molecular smoking
gun," observes Macko. His group is now
exploring how exercise affects TNF-alpha
levels: Can it reduce the protein to nearnormal
levels, and is that part of how
exercise can help stroke patients regain
function?
Exercise found to thwart
diabetes in stroke patients
Related studies at the Baltimore VA are
probing other biochemical effects of
exercise—particularly its beneficial impact
on insulin resistance and the risk of
diabetes. Even as they continue to explore
the exact mechanisms involved, Macko’s
team now has evidence, he says, that
"treadmill aerobic training can improve
glucose tolerance to prevent and even
reverse diabetes in [the stroke] population."
In fact, exercise—both aerobic and
strength training—is being validated in many
studies as great medicine for stroke patients.
Still, Macko doesn't rule out the possibility
that his team may hit on a protein or other
molecule that can be manipulated to achieve
similar therapeutic effects.
Macko: "The question is, will we able to
do what was done in rats and use
pharmacological or genetic mechanisms to
overexpress these molecules? It's
conceivable that we could use these sorts of
biological regulatory signals to help people
even more than the exercise could or to help
those who may be unable to train."
Taking advantage of
'neuroplasticity'
Future lab breakthroughs aside, Macko
says one of the most exciting findings to
date from studies by his group and others is
that people can regain function even many
years after a stroke. Typically, stroke
patients have been told to accept their
disabilities as permanent, whereas survivors
of heart attacks, for instance, are often put
on exercise regimens to rebuild their
strength and endurance. Most stroke
rehabilitation programs focus on short-term
recovery and end just a few months after the
patient’s stroke. As a result, improvements
level off and fitness and mobility wane over
time—which itself can raise the risk of a
second stroke, diabetes or other diseases.
But experts are moving toward a new
approach, thanks to research such as a
recent treadmill study led by Macko. According to George
Wittenberg, MD, PhD, a neurologist at the
Baltimore VA who is helping to lead a
multisite VA clinical trial on robots in stroke
rehabilitation, research has led to a new
understanding of brain "plasticity"—the
ability of the brain to form new neural
pathways and "rewire" itself to restore lost
function.
"The older thinking was that
approximately a year after a stroke, there
wasn't any useful neuroplasticity and that
further therapy wouldn't have any further
effects on motor function," says Wittenberg.
“But there have now been several studies
using a variety of techniques that have
shown … that there is plasticity that goes on
long after a stroke."
That's good news for people like 69-
year-old veteran Earl Elsey Jr., who suffered
a stroke in 2004. For the past six months,
he’s been using a treadmill three times per
week at the Baltimore VA as part of a study
on how different types of exercise—
stretching, intense walking, or longer duration
walking—affect fitness, balance,
walking ability, and everyday function. He
says his fitness and balance are “80 percent
better” and notes that he's been able to
reduce his medication for both diabetes and
high blood pressure. Most of all, he credits
the education he’s received through the
study as a key factor in his motivation to
keep on exercising. "Not only have I
improved physically since coming here,"
says Elsey, "but I've learned about all the
things I can do to deal with stroke. I've
learned how to take care of myself."
|
