Over the past decade a kind of brain surgery known as deep-brain stimulation (DBS) has helped some Parkinson's disease sufferers develop better control of their physical movements. But the risks that come with the invasive procedure—not to mention the costs—keep physicians and patients cautious. The treatment is usually indicated when medicine no longer addresses the neurodegenerative disorder's symptoms effectively. Now, a new study from European researchers indicates that deep-brain stimulation's benefits are just as promising for people in the earlier stages of Parkinson's.

"The conclusions of this study are really exciting," says David Charles, the chief medical officer of the Vanderbilt Neuroscience Institute and director of the movement disorders clinic there. "Most likely it will be a transformative study in our understanding of when to apply deep-brain stimulation therapy in Parkinson's disease."

Parkinson's disease is a disorder of progressive decline. The tremors, rigidity and difficulty moving are often treated with anti-Parkinson's medications such as levodopa at first. But as the disease marches forward, the benefits fall off. The same dose no longer lasts as long, patients experience unpredictable cycles in their ability to move, and struggle with excessive movements called dyskinesias that make their limbs jump and flail involuntarily. This stage of the disease, which many people reach in their mid-60s, is when some decide to undergo DBS.

Researchers at several French and German institutions enrolled 251 people with midstage Parkinson's disease in a multicenter trial to see if DBS was helpful for individuals in earlier stages of Parkinson's. On average the study participants had been living with the disorder for 7.5 years and were 52 years old—younger and earlier in their disease progression than is typical for those undergoing DBS. Quality of life was assessed by a standard 39-question survey that included questions about well-being, discomfort, mobility and daily life activities. For example, the survey asked how often study subjects had difficulty carrying shopping bags, whether they had problems walking half a mile or 100 yards or whether they felt frightened or worried about falling over in public.

Participants reported a 26 percent improvement in quality of life after receiving deep-brain stimulation and medication for two years. They slept better, which gave them the energy to cope with more stressful situations, says one of the study's co-authors, Günther Deuschl, a professor of neurology at Christian-Albrechts University of Kiel in Germany. Also, instead of having to deal with unpredictable periods of immobility, people were able to make appointments and schedule social activities, he adds. A parallel group that received only standard medical therapy reported a 1 percent decrease in quality of life. In addition, participants in the experimental group reported better mobility, which was backed up by video assessments. The results are published in the February 14 issue of The New England Journal of Medicine.

The study demonstrates that DBS combined with medicine is better than the latter alone when the procedure takes place at an early stage of Parkinson's, Charles says, adding, "It's not as if it was a little bit better. The numbers on quality of life and motor performance were dramatic." He was not involved in the new study but is conducting a U.S.-based pilot study to examine the effects of DBS on subjects in the early stages of Parkinson's.

How risky is DBS surgery?
Complications and problems with the brain surgery include infections and an estimated 2 to 3 percent risk of brain hemorrhaging, the latter of which could sometimes result in paralysis, stroke or speech impairment. Rarely, leaking cerebrospinal fluid can cause headaches or life-threatening meningitis. Most side effects, however, involved minor infections of the surgical site itself that can be treated. The European researchers recorded 26 problems related to the surgery, which included movement of the electrode that required reoperation and impaired wound healing. All but one was temporary—one participant was left with a scar, Deuschl explains. He also notes that there were three suicides (two in the deep-brain stimulation group and one in the medical therapy–only group) as well as four suicide attempts (two in each group).

The increased risk for suicide in both study groups is not a surprising result. Suicide and depression are associated with Parkinson's disease, Deuschl says, but he suggests that because there was no significant difference between the surgery and med-only groups it is possible that people who are interested in DBS are risk-takers. "We have to be very careful when we offer this to patients," he says. "Those patients who belong to this risk-taking category should be warned and monitored."

The medical technology company Medtronic manufactures some components for the deep-brain stimulation device used in the study and Charles's pilot study. Charles, Deuschel and many of the other researchers involved in the new study receive grant support as well as lecture and/or consulting fees from Medtronic.

There can be no denying that taking a pill is a lot easier than undergoing DBS. The procedure first requires an invasive surgery to put a thin metal electrode on the brain’s surface. The new study targets a region called the subthalamicnucleus, which is tucked in the brain center and above the spinal cord, hence the name deep-brain stimulation. Other procedures might place the lead on the neighboring thalamus or the globus pallidus. All three regions are involved in controlling movement. Next, a pulse generator, which sends a small electric current to the targeted brain region much like a pacemaker does to the heart muscle, is implanted below the skin in the chest or abdomen. Insulated wires run from the implanted lead through the skin of the head, neck and chest to the pulse generator.

The pulse generator sends a continuous electrical signal to the targeted regions. In Parkinson's those regions are abnormally active and the stimulation regulates electrical signals between nerve cells. Scientists still do not understand how this relieves motor problems exactly, Charles says. They do know that for patients in advanced stages of the disease neither drugs nor stimulation works, perhaps because the connections between motor neurons or their ability to receive the neurotransmitter dopamine is too deteriorated, Deuschl says.

The entire treatment can involve multiple surgeries, thus multiplying the risk of complications—and treatment is expensive. The Parkinson's Disease Foundation, which funds research, education and advocacy, states that the procedure, implant and accompanying appointments can cost about $100,000 (pdf). Parkinson's medication rings in at about $2,500 per year, says James Beck, who is director of research programs for the foundation and not involved in the new work. Deep-brain stimulation can partially reduce the need for and thus the cost of medication. The procedure and medication can be covered by Medicare or private insurance (provided patients have insurance). "To the individual the costs are less," he adds. "But there is a societal cost that can be quite expensive."

Due to the costs and risks, Beck recommends that people considering DBS find a medical facility that has well-established expertise and resources. With that caution in mind, Beck says the new study "bodes well for individuals who elect to take this route earlier."

The European's studies finding that earlier treatment works jibes with studies examining deep-brain stimulation in people with more advanced Parkinson's disease, Deuschl says. The results also open the possibility that the procedure could offer more than alleviation of symptoms. "The most important question is: 'How does this group do in the long run?'" he says. "We would like to know if this improvement is maintained for seven to eight years or if they deteriorate over time." If the researchers observe a decrease in the rate of disease progression as compared with the medicine-only group, he says, that would indicate that early intervention could change the course of the disease.