With Each Advance in Parkinson’s, a Question
People who study brain disorders say they know more about Parkinson’s disease than just about any other. That’s a tribute to the brain’s awesome complexity. The long list of unanswered questions about Parkinson’s is growing shorter at an agonizingly slow pace.
To researchers, each unanswered question is a challenge. They know that Parkinson’s cascade of symptoms--tremor, bad posture and slowness of movement for starters--occurs because certain nerve cells in the brain die. But no one knows what kills them, and whoever finds the answer will become rich and famous. Whoever finds a way to stop the process, thereby curing the disease, will become 10 times more so.
But to patients, the unanswered questions are a source of continual frustration and unease. I know. I’ve had the disease for a dozen years, and I’ve studied it about as carefully as a layman can. And I still have great difficulty making choices about the proper course of treatment.
When, for example, should we start taking levodopa? This is the drug that helps the brain make dopamine, the chemical that the dead brain cells no longer manufacture. Dopamine is a critical part of the circuits in the nervous system that enable ordinary movement.
One school of thought is that levodopa, although it makes us feel good now, is bad for our long-term health. The more we take it, the less effective it becomes and the worse the side effects grow. After some amount of total use, levodopa does more harm than good. If this view is right, we should abstain from levodopa until Parkinson’s symptoms make us barely able to function.
Another view, held by equally eminent scientists, is that levodopa does no long-term damage and may even do good. True, its bad side effects ultimately overtake its benefits. But the timing depends on Parkinson’s natural destruction of brain cells, not on how much levodopa has been swallowed. If this view is right, it doesn’t matter how much levodopa we take during Parkinson’s early phases. In fact, if we refrain from taking levodopa too long, we’ll suffer some problems (muscle deterioration, for example) that cannot be reversed when we finally take levodopa.
Who’s right? Darned if I know. Thirty of the world’s leading Parkinson’s experts convened a meeting in Paris in 1998 to cut through the uncertainty and develop a consensus that would guide neurologists as they advise their patients. But the consensus conference couldn’t reach a consensus. The majority view was that levodopa is not harmful in the long term and that it should be used to preserve quality of life while the quality of life is still worth preserving. But there was plenty of disagreement. Three eminent American specialists, for example, said they had seen no proof that levodopa does not kill cells in the substantia nigra, the portion of the brain where dopamine is produced.
In my uncertainty, I try to take enough levodopa to keep functioning--but no more. Sometimes I skimp too much. When that happens at work, I close the door to my office and shake in private until my next levodopa pill kicks in. If it happens while I’m driving and there are no other drivers with me who can take the wheel, I pull off the road and walk until I steady down.
Sooner or later, the pills can no longer lift us out of total misery. What do we do then? The best answer as of today: See a brain surgeon. But don’t expect any easy choices. Uncertainty likewise clouds the decisions about whether and when to undergo any of the available brain surgeries.
One kind of surgery aims at masking Parkinson’s symptoms after the pills no longer do the job. An electrode is lodged in one of several parts of the brain, along a neural circuit that is overactive in Parkinson’s. From the electrode, a wire runs under the skin to a pacemaker that is implanted under the collarbone. A magnet passed over the pacemaker can turn the electrode to high, low or off, depending on the need. Each jolt of electricity delivered by the electrode has the effect of short-circuiting part of the overactive circuits and restoring them to normal.
The operation seems to work pretty well--when it works. Two of my friends found themselves much more mobile after the operation was performed on one side of their brains. But as with all surgeries, particularly in the brain, there are dangers. As it happens, both of my friends tried the same operation a second time, on the other side of the brain. Both of them suffered bleeding within the brain, and one had to stay in the hospital for several weeks to recuperate. Another operation, at once more experimental and more familiar, holds the potential to cure the disease. Living brain cells from an aborted 7-week-old fetus are injected into the damaged part of the brain and, if all goes well, make themselves at home and replace the cells that have died.
This operation, which ran afoul of the anti-abortion movement, is all but impossible to get today in the United States. But during the Clinton administration, the government approved two trials of the procedure, with half of the participants receiving fetal cells and the other half, a control group, undergoing a sham operation in which no cells were actually delivered. The participants were told that those who underwent the sham operation could get the real thing when the trial was over. (Dr. Curt Freed, the lead researcher for this trial, has written a lively account of fetal transplantation, called “Healing the Brain.”)
In keeping with Parkinson’s treatments, the trial yielded mixed results. The good news is that the fetal cells took hold in most of the patients. The bad news is that for a few, the cells took hold with a vengeance and manufactured too much dopamine, which left these patients with writhing motions (called dyskinesias) that they couldn’t easily control.
One of these five is George Doeschner. He got the sham operation the first time and chose to get the real thing when the trial was over. Although he was judged to have a dopamine surplus after the real operation, he was able to return to his job as an electrician in downtown New York office buildings.
Last Sept. 11 found him on the 34th floor of the first of the two World Trade Center towers to be struck by hijacked jets. Despite his “disability,” he walked down 33 flights of stairs to safety before the tower collapsed. Now, nearly a year later, he’s still working, and a couple of months ago he had his first job back in the financial district. “From where I was working, I had a great view of the hole in the ground,” he said. “It was spooky.”
And the trial produced a further ambiguity.
Although the fetal cells thrived in nearly all of those who received them, they seemed to relieve the symptoms only of those 60 and younger. Doeschner was 55 when he had the operation, but I’m now 59. Does that mean I have to move fast or it will be too late to benefit from this form of treatment? I think not; I suspect that the magic 60-year-old line was a product of the trial’s design, not of any magical change that occurs in Parkinson’s brains at age 60.
But the 60-year threshold introduces a new uncertainty. On the one hand, I’d like to wait as long as possible to get this operation. That might give researchers time to figure out what kind of cells to use (brain cells grown from stem cells may work better than fetal cells), how many of them to use and exactly where to put them. On the other hand, I don’t want to wait so long that the fetal cells won’t relieve my symptoms.
Which is the right course? Darned if I know.
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Joel Havemann, an editor in The Times’ Washington bureau, is the author of “A Life Shaken: My Encounter With Parkinson’s Disease” (Johns Hopkins University Press, 2002).
