Copyright 1995 Globe Newspaper Company
 
   Surgery and transplants show new promise for Parkinson's; AGING /
                             JUDY FOREMAN
 
The Boston Globe, June 19, 1995, Monday, City Edition
SCIENCE & TECHNOLOGY; Pg. 29; 1785 words
By Judy Foreman, Globe Staff
STANFORD, Calif.
 
Until recently, Richard Weeden, 49, a mechanical engineer from
Portsmouth, R.I., was losing his 20-year battle against Parkinson's
disease.
 
So was Tony Johnson, 57, a civil engineer from Taunton.
 
Day after day, like many of the 1.5 million similarly stricken
Americans, they endured the ping-pong hell of Parkinson's - bouncing
between rigidity caused by the disease, which can make even turning
over in bed impossible, and the jerky movements caused by the medicine
used to treat it.
 
Like many other patients, Weeden and Johnson initially had good
results with the medicine, L-dopa, that they took to supply a critical
brain chemical, dopamine, that Parkinson's patients lack.
 
When L-dopa works - the moments patients call "on" time - the tremors,
ridity and slow movements of Parkinson's improve.
 
But as a videotape of Weeden makes painfully clear, there are also
horrible side effects: movement disorders called dyskinesias. For
Weeden, this meant walking with a lurching goose-step that was so
awkward he often fell. Even when he was seated, his legs did a bizarre,
jerky dance.
 
During the "off" times - when L-dopa suddenly stops working, sometimes
after years of effective treatment - patients can barely move. When
that happened, Weeden was often reduced to crawling.
 
Today, Weeden and Johnson - and hundreds of patients like them - are
cautiously excited about surgical treatments that are sweeping like
wildfire through the once-quiet world of Parkinson's.
 
The approach Weeden chose is a revival of an old operation,
pallidotomy, that was used decades ago to treat Parkinson's. It was
all but forgotten when L-dopa - the drug featured in the movie
"Awakenings" - was introduced in the 1960s.
 
Pallidotomy can reduce the tremors, rigidity and side effects of
L-dopa, though it does not fix the underlying dopamine deficiency. A
similar operation, called deep brain or thalamic stimulation, can
also help reduce tremors.
 
A very different operation, which Johnson had, involves transplanting
fetal cells capable of supplying the missing dopamine to the brain, a
potential solution to the basic problem.
 
Together, these operations are bringing about a dramatic shift in
Parkinson's care and stirring palpable hope among newly-energized
patients, who cruise the Internet to stay steps ahead of their
doctors.
 
Neurologists, who once held all the cards - chiefly, drugs like
L-dopa (Sinemet), Deprenyl and newer ones called COMT inhibitors - now
watch as neurosurgeons rush in, scrambling to learn - and improve on -
pallidotomy techniques that went out of style before some of them
were born.
 
So far, pallidotomy is still available only at selected centers, but
the list of hospitals performing it is exploding.
 
At Loma Linda University Medical Center in California, Dr. Robert
Iacono has done so many pallidotomies - 500 at last count - that he
has won both fame and infamy, the latter among doctors who see him
as flamboyant and even "dangerous."
 
At Emory University in Atlanta, pallidotomy pioneer Dr. Mahlong
DeLong and colleagues have done 76 pallidotomies since December, 1992.
They claim a 90 percent initial success rate and have 400
patients on their referral list. It's a 3-year wait for surgery for
those accepted.
 
In Boston, Dr. G. Rees Cosgrove, a neurosurgeon at Massachusetts
General Hospital, has done 25 pallidotomies, and surgeons at Boston
University and Deaconess Hospital are gearing up to start.
 
Leading specialists, among them Cosgrove and BU neurologist Dr.
Samuel Ellias, warn that the operation isn't for everyone,
particularly not those who have dementia or other neurological
problems that mimic true Parkinson's.
 
In rare cases, the operation, still considered experimental,
causes partial blindness or partial paralysis. Furthermore, despite
almost-miraculous initial results, it is far from clear whether the
operation's benefits will be long-lasting.
 
Despite the reservations of those who doubt the wisdom of treating a
disease that kills brain cells by killing more brain cells, there
seems to be no stopping the pallidotomy stampede, which began in
1992 when a neurosurgeon in Sweden, Dr. Lauri Laitinen, published a
report on about 40 patients. Initially, the vast majority found that
their rigidity and tremors improved, but longterm results are not
out yet.
 
In a pallidotomy, surgeons make cuts, or lesions, on one or both sides
of the globus pallidus, an olive-sized area of the brain that is
crucial for normal movement. So long as there is enough dopamine,
these cells fire normally. But when there's no dopamine, the cells
fire abnormally, says Dr. Ole Isacson, director of the neuroregeneration
lab at McLean Hospital in Belmont.
 
Destroying these abnormally-firing cells, neurosurgeons believe, will
often restore normal movement. But even those who do the operation
acknowledge its limits.
 
"All we do is change the manifestation of the disease," says Cosgrove
at MGH. "This is not a cure for Parkinson's disease. I am quite sure
that Parkinson's will continue to progress as it would do without the
operation."
 
"You are not fixing the problem, you are just trying to make the
system compensate," agrees Dr. C. Warren Olanow, head of neurology
at Mt. Sinai School of Medicine in New York, though he says
his team, too, is "tooling up" for pallidotomy.
 
But Olanow's team, like Parkinson's specialists at a handful of
other medical centers, is also experimenting with another method,
called deep brain, or thalamic, stimulation.
 
So far, about 50 patients nationwide, including two at the Deaconess
Hospital in Boston, have had this surgery, which aims to incapacitate
cells in the thalamus, another part of the brain's movement circuitry.
 
Years ago, surgeons killed cells in the thalamus to control tremors,
just as they do in pallidotomies today. But now, says Dr. Daniel Tarsy,
chief of neurology at the Deaconess, researchers believe they can get
the same effect by simply overstimulating these cells with electrical
signals from a pacemaker implanted in the patient's chest.
 
The advantage of thalamic stimulation, he says, is that "you do not
actually damage tissue - you jam the circuits." And initial results,
at least in Olanow's view, "are terrific."
 
Still, for many patients, pallidotomy remains the hot topic.
 
Weeden first tried it in 1993 in Sweden, with Laitinen operating and
Cosgrove observing. It didn't work - the electrode had been placed in
the wrong area.
 
Last year, back in Boston, Weeden tried again, this time with Laitinen
watching and Cosgrove operating on the left side of Weeden's brain to
improve symptoms on the right side of his body.
 
The outcome was sweet. Weeden had entered the hospital in a wheelchair -
and walked out under his own steam. Two weeks ago, he had a pallidotomy
on the other side.
 
So far, he is still unable to go back to work, and no one knows how long
the effects will last.
 
But he is delighted nonetheless. His goose-stepping is gone. He can do
light housework and take walks.
 
"I'm not 100 percent back" to normal, he says, "but compared to where
I was, this is a wonderful place to be."
 
1. Transplant success debated
 
In April, Tony Johnson, 57, a civil engineer from Taunton, became the
first person in the world to have brain cells from fetal pigs implanted
in his brain to combat Parkinson's disease, which he has had for 27 years.
 
Neurosurgeons have been experimenting since the early 1980s with
implants of human fetal cells in Parkinson's patients. They have had
considerable success but aroused moral and and legal opposition from
abortion opponents, because the cells came from aborted fetuses.
 
The implanted fetal cells take up residence in the patient's brain
and begin supplying the dopamine that Parkinson's patients lack.
 
Over time, the implants reduce by about half the rigidity and slowness
of movement of Parkinson's and can reduce to nearly zero the "off" time
that patients suffer when medication stops working, says Dr. Ole
Isacson, director of the neuroregeneration lab at McLean Hospital.
The implants appear less effective against tremors.
 
So far, about 25 fetal transplants have been reported in the medical
literature, but neurosurgeons estimate that hundreds have actually
been done, despite debate about the surgery's effectiveness.
Some argue that because patients are desperate, any promising
intervention could appear to make patients better through the
placebo effect alone.
 
To settle that question, Dr. Curt Freed, director of neurotransplantation
for Parkinson's at the University of Colorado School of Medicine, has
embarked on a controversial study of 40 patients.
 
His team will make small holes in the skulls of all 40 patients. Twenty
will have needles inserted through the holes and fetal tissue injected
into their brains, but the other 20 will not - a kind of "sham" surgery.
 
Neither the patients nor a team of doctors who will evaluate them in
New York will know who got which surgery. As of last week, the team had
operated on four patients.
 
Though it will take time to get results from Freed's study, many
neurosurgeons are optimistic about fetal tranplants, among them Dr.
James Schumacher of the Lahey Hitchcock Clinic in Burlington. He
has been working with Isacson to find ways to use fetal pig cells
instead of fetal human tissue.
 
The advantages are clear, they say. To get enough human tissue for one
transplant, surgeons must get fetal tissue from several dozen women
undergoing abortions within a two-day period. Then testing must be done
to be sure the tissue is free of viruses like HIV or Hepatitis B.
 
By contrast, says Schumacher, "Pigs don't have AIDS. These animals
are raised in a strict environment. They are screened for every
pathogen known, so they are cleaner and more plentiful."
 
It is too soon to tell how well the pig cells are working for Johnson,
but Johnson's wife, Mildred, says they have "made the 'on' times much
smoother and longer, his speech is much better, he can walk better and
he's definitely turning around. You can see signs the cells are starting
to work.. . .
 
"It's almost like miracle."
 
2. For more information
 
For more information on Parkinson's disease, you may call:
 
- American Parkinson's Disease Association - 1-800-223-2732.
 
- American Parkinson's Disease Association Information and Referral
Center - 617-638-8466. This number also connects you to the
Parkinson's Disease Program at Boston University.
 
- Massachusetts Chapter of the APDA - 1-800-343-3383.
 
- Young Parkinson's Support Network - 617-527-2803.
 
- To obtain information via World Wide Web, the address is:
http://neuro-chief-e.mgh.harvard.edu/parkinsonsweb/Main/PDmain.html
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