Return to surgery reawakens hope on Parkinson's

THE BALTIMORE SUN

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, Mass.

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, L-dopa, used to treat it.

Today, Mr. Weeden and Mr. 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 Mr. 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 deficiency of dopamine, a critical brain chemical.

A very different operation, which Mr. 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.

When L-dopa works -- the moments patients call "on" time -- the tremors, ridity and slow movements of Parkinson's improve.

But there are horrible side effects: movement disorders called dyskinesias. For Mr. Weeden, this meant walking with a lurching goose-step. He often fell. Even when he was seated, his legs did a jerky dance.

During the "off" times -- when L-dopa suddenly stops working, sometimes after years of effective treatment -- patients can barely move. Mr. Weeden was often reduced to crawling.

A three-year wait

Now the future appears to lie not in the hands of drugs like L-dopa (Sinemet), Deprenyl and newer ones called COMT inhibitor, but in the surgical techniques that neurosurgeons are scrambling to improve. So far, pallidotomy is 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 three-year waiting list.

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 Dr. 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. And despite almost-miraculous initial results, it is far from clear whether 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 improved, but long-term 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, Mass.

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 Dr. Cosgrove. "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 Mount Sinai School of Medicine in New York, though he says his team, too, is "tooling up" for pallidotomy.

But Dr. 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 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 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, he says, is that "you do not actually damage tissue -- you jam the circuits." And initial results, at least in Dr. Olanow's view, "are terrific."

So far, so good

L Still, for many patients, pallidotomy remains the hot topic.

Mr. Weeden first tried it in 1993 in Sweden, with Dr. Laitinen operating and Dr. Cosgrove observing. It didn't work -- the electrode had been placed in the wrong area.

Last year, back in Boston, Mr. Weeden tried again, this time with Dr. Laitinen watching and Dr. Cosgrove operating on the left side of Mr. Weeden's brain to improve symptoms on the right side of his body.

Mr. Weeden had entered the hospital in a wheelchair -- and walked out. Two weeks ago, he had a pallidotomy on the other side. 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."

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