"I thought, 'Oh, my God, that's brain surgery,' " recalls Bill Schmalfeldt. He was considering participating in a clinical trial—the only one testing so-called deep brain stimulation in patients with early-stage Parkinson's disease—that might result in electrodes being permanently implanted deep inside his head. Diagnosed with Parkinson's disease at age 45, Schmalfeldt, now 54, found himself trolling several years ago for a research study he could join. Why? His work as a public liaison for the National Institutes of Health involved doing podcasts "extolling the value of clinical research."
He had understandable reservations. "You'd be insane not to have some worries about it," he says. Any surgery carries risk, and deep brain stimulation (DBS), a form of brain stimulation therapy, involves drilling at least one hole in the skull to snake electrodes to precise locations far into the cavernous folds of gray matter. Though it rarely happens, a brain bleed during the DBS procedure can leave a person dead.
Pushing his worries aside, Schmalfeldt underwent the DBS surgery in June of 2007. The procedure included having a battery pack implanted in his chest to drive the electrical stimulation in the electrodes that act to jam dysfunctional signaling in the brain. While he got randomly assigned to get DBS, other patients who volunteered for the study were not given the surgery but periodically undergo the same eight-day stretches of medical observation at Vanderbilt Medical Center in Nashville.
DBS was first approved by the Food and Drug Administration in the late 1990s and is now approved to treat movement disorders, like tremor; dystonia, which causes involuntary muscle contractions; and Parkinson's, for which DBS is typically used when patients can no longer rely on medications to manage their worsening symptoms. A study in the Journal of the American Medical Association in January found that subjects with advanced Parkinson's had an improved quality of life and about four more hours per day of freedom from troubling motor control symptoms than did those undergoing the best medical therapy.
"To study any treatment that might slow progression, you have to study it very, very early" in the course of a patient's illness, says neurologist David Charles, an associate professor at Vanderbilt University School of Medicine and lead researcher in the trial in which Schmalfeldt is participating. Because DBS isn't offered until a patient's symptoms have stopped responding well to medication, he had to get special FDA approval for the trial. Medtronic, the maker of the only approved DBS device, is a partial sponsor of the research, says Charles.
In Parkinson's patients whose medications' power is diminishing, "DBS is almost standard-of-care," says Kendall Lee, assistant professor of neurosurgery and physiology at the Mayo Clinic in Rochester, Minn. While the nuances of the underlying mechanisms are not well understood, "DBS appears to be like a drug, able to evoke the release of neurotransmitters," he explains. One advantage DBS offers is its specificity, he says. Exact placement of the electrodes relies on the patient being awake during surgery, so they can be asked questions about pain or be asked to perform different movement tasks that will guide the surgeon. Another advantage, says Lee, is that DBS is reversible—that is, the level and rate of stimulation can be changed or stopped. The patient also controls the device, which can be turned on or off by waving a controller over the battery in his or her chest.
Such positives have inspired a flurry of clinical investigation into other possible applications for DBS, which might extend beyond Parkinson's and movement disorders. "The brain really controls everything," says Lee. Where medications and other treatments fail, DBS might prove to be a viable option. The widening list of targets may include depression, cluster headache, Tourette's syndrome, craniofacial pain, and obsessive-compulsive disorder; clinical trials in those areas are currently underway or have been completed. "The future looks really bright for DBS," Lee says.
Yet the therapy Schmalfeldt hoped would offer him neuroprotection is proving fallible. While he experienced a welcomed lessening of the rigidity and slowness in his movements with DBS, his balance and gait have deteriorated significantly in the last year, he says. A positive of the treatment, he says, is that he now takes about half as much of the Parkinson's anti-tremor medication, Levodopa, than he would otherwise be taking. Over time, a patient's Levodopa dose must be increased, which causes side effects including dyskinesia, an increase in involuntary—often jerky—movement, in a majority of patients.
Other volunteers who got DBS in the trial have had better luck. "I would say my Parkinson's disease does not seem to be progressing," says Duane Cook, 56, a lawyer from Lexington, Ky., who also had the DBS device implanted. In fact, Cook, an avid exerciser, says, "My golf game has continued to improve." At this stage, it is impossible to know the impact of DBS on the disease progression in the two men.
Schmalfeldt says he has had a number of falls lately. The recent JAMA research found an increased risk of falls in patients who had DBS. What is not clear is whether DBS was responsible or whether the subjects were at higher risk because of better overall functioning and their higher level of activity. Research has suggested other DBS side effects may include post-operative psychiatric complications, like sexual disinhibition, pathologic gambling, and transient psychosis. Other DBS research, though not conclusive, has suggested side effects may include an increased risk of depression or suicide. Also, the battery must be replaced at least every five years, typically in an outpatient setting.
Though Schmalfeldt has experienced a decline in functioning, he retains a buoyant, cheeky attitude. To offer support to other Parkinson's patients and to show that "it can be done with a sense of humor," Schmalfeldt blogs about life with Parkinson's at DeepBrainDiary.com. "You have to laugh at it," he says of the inconveniences of the disease. "I call it 'taunting the monster.' "
Corrected on 07/16/09: An earlier version of this article misstated the name of David Charles of Vanderbilt University School of Medicine, and incorrectly described a symptom of Parkinson's disease as a side effect of the Parkinson's drug Levodopa. Also clarified was the fact that deep brain stimulation may require drilling more than one hole in the skull.