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 John Cottingham "The parkinsn list brings Knowledge, Comfort, Hope, and Friendship to the parkinsonian world." Parkinson's Chat on the Undernet 8:30 PM CST -6 Daily. If you access the Internet through a provider with a [log in to unmask] PPP/SLIP account, free IRC chat software is available. WFD