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EXPERIMENTAL MEDICINE

Deeply Stimulating Brain Surgery
for Parkinson’s Patients


And so, having come this far, you find yourself lying on a table in the operating room, waiting for a man to drill into your skull and insert two metal stimulators into your brain. You undoubtedly wish you were someplace far away. But since your head is locked in a stereotactic headframe, and since you are paying a lot of money to go through all this, you can’t leave, and you probably won’t complain.
    After all, you have Parkinson’s disease, which has been making your life a hellish declension of tremors and muscular rigidity, and you know that unless you do something radical, the future looks even worse. And so you lie there and wait—knowing that, if all goes well, your tremors will be significantly reduced and your quality of life significantly upgraded.
    The surgical process in question is known as deep-brain stimulation (DBS) of the sub thalamic nucleus (STN). Essentially, it involves implanting two electrodes deep in the patient’s brain, in the tiny (six-to-eight millimeters) STN region. The electrodes, or stimulators, are powered by pacemaker-like devices implanted under both collarbones. By stimulating the neurons, they somehow alleviate the tremors and the muscular rigidity.
    Although it has been approved for use in France for six years, and has yielded positive results, DBS is still considered an experimental procedure in the United States, and only a small number of the operations have been performed here. As of mid-December, Dr. Gordon Baltuch, assistant professor of neurosurgery, and a team from the Neurological Institute had performed 33 of them at Pennsylvania Hospital. (Both the hospital and the Institute are part of Penn’s Health System.)
    Parkinson’s disease (PD) is caused by a shortage of the dopamine enzyme, a neurotransmitter produced in the brain that controls movement. While a drug called levadopa (Sinemet) can provide some relief by replacing the dopamine, it gradually loses its effectiveness.
    The stimulators emit electrical impulses that alter the brain signals responsible for the tremors, but exactly how they do so is not clear. Baltuch says that it may “jam the circuit”—which, for some reason, has gone haywire—in the basal ganglia part of the brain, where the dopamine transporters reside. Instead of “stimulation,” he suggests, a more accurate phrase would be “deep-brain modulation.”
    “There are a whole variety of theories as to what this could potentially be doing which are not really well understood,” explains the quick-talking, Canadian-born Baltuch. “One of the theories is that by inhibiting a hyper-excitable path, you tune down the hyper-excitation to the thalamus and you allow it to work. So it’s sort of a series of gates and channels and inhibitions and excitations—Parkinson’s disease is caused by a change in dopamine, but [DBS] results in a whole changing in the basal-ganglia circuitry. But at present, people do not really understand what [DBS] is doing at a neurochemical level.”
    If the disease is too far advanced, or if the patient is too old or in frail health, the procedure is not considered worth the risk. (Of the 33 procedures Baltuch has undertaken, one resulted in death; a patient died three days after the operation from a pulmonary embolism. A more common problem is bleeding in the brain, which can lead to a stroke or death.) Then there’s the matter of getting your insurance company to pay the cost (roughly $50,000 to $70,000) for an experimental procedure, though Baltuch suggests that if and when it is approved by the FDA, “the insurance companies will have less of a choice.”
    The team uses an MRI (magnetic-resonance imaging) scan of the brain to pinpoint the subthalamic nuclei. When they find the one on the left side, they drill a small hole in the frontal portion of your skull, and insert a stimulator into your brain. Then they call for silence and listen as the electronically amplified cells of your brain make their strange whirring and popping sounds while the team guides the stimulator to the precise location. Eventually, if all goes well, they hear the sound they want, signaling that the implant is in the right spot.
    After another MRI, Baltuch sews up the hole, and then fires up his drill to make a hole on the right side. Since the two sides of the brain are symmetrical, it’s easier to locate the correct spot this time around.
    The stimulators are powered by magnetic battery packs inserted beneath the collarbones, a separate procedure that requires a general anesthesia. They also have to be programmed to give the right amount of electrical impulse. The batteries have a life-span of three to five years, but Baltuch says it takes about 15 minutes to change them, and he hopes that a rechargeable battery will be developed.
    “Deep-brain stimulation is reversible,” says Baltuch. “Let’s say there was a cure for PD one day—the possibility exists. You could just take these stimulators out or turn them off, and no bad effect would be done to the brain. We have actually demonstrated that.”
    It is, he acknowledges, an expensive procedure. “But I think it’s hard to put a price on giving someone increased functionality, especially in someone who is young and otherwise healthy.
    “I think it’s an exciting therapy,” he adds. “My hope is that the pharmaceutical companies can figure out neurochemically what STN does, and can somehow figure out a way to mimic what STN stimulation does pharmaceutically so you can take it in a pill.”


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Copyright 2001 The Pennsylvania Gazette Last modified 3/6/01