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Brain Stimulation Results Pinpointed in Parkinson's

Electrodes improve balance, movement when drug levels dip, says study

MONDAY, Nov. 26, 2001 (HealthDayNews) -- Bolstering patient reports that electrical stimulation deep within the brain may lessen trembling and other symptoms of Parkinson's disease, a new study pinpoints and quantifies the effects, possibly paving the way for use of fewer drugs with fewer side effects than current standard therapy.

The electrode-based therapy, called deep brain stimulation (DBS), seems to improve movement in patients even when levodopa, a drug commonly used to control the naturally produced compound of the same name, is not working.

While previous studies of DBS relied on patient reports of improved motion, the latest study used standard tests to measure changes in motor functions typically affected by Parkinson's disease. Findings appear in the Nov. 27 issue of Neurology.

Parkinson's disease is a motor system disorder caused by the progressive loss of dopamine-producing brain cells. Without dopamine, cells that control movement fire out of control, leading to trembling in the hands, legs and face and stiffness of the limbs and trunk. Patients also move slowly and develop impaired balance and coordination. Giving people dopamine to replace the loss doesn't work because it can't cross the brain barrier. However, levodopa, a precursor to dopamine, can.

The disorder affects up to 1.5 million Americans, and while certain drugs, including levodopa, can improve symptoms dramatically, there is no cure.

As the disease progresses, the brain is increasingly unable to store levodopa and convert it to dopamine. As levodopa concentrations in the blood rise and fall, symptoms of Parkinson's disappear ("on-time") and reappear ("off-time"), and therapy becomes less effective.

A small subgroup of patients who respond to levodopa are candidates for DBS, which involves implanting electrodes deep within the brain and adjusting how intensely and how often they fire to achieve the greatest results in each patient.

Lead investigator Dr. John Nutt, professor of neurology at the Oregon Health Sciences University, in Portland, says little was known about how DBS affects the brain's response to levodopa to improve the symptoms of the disease.

Nutt and his colleagues enrolled 12 patients with Parkinson's. Six had electrodes implanted in a brain region called the globus pallidus interna (which, among many other functions, controls posture), and six had implants in the subthalamic nucleus. Both movement-related areas deep in the brain are the usual targets for DBS.

While hospitalized, the volunteers were observed every waking hour for 48 hours while on their usual levodopa medication. On one day, their DBS was turned off, although neither the patients nor their nurses knew when the DBS system was on or off.

On both days, the researchers evaluated the patients' ability to tap a finger as quickly as possible and to stand up and walk. They also rated the patients on standard tremor and involuntary movement scales.

"The patients, as a whole, were improved by deep brain stimulation," says Nutt.

Nutt found that when the patients' levodopa was working (the "on-time"), DBS improved motor function by 29 percent. But when levodopa wasn't working, DBS improved motor function by 38 percent.

When the DBS system was on, patients were able to tap their finger 23 percent faster on average, while walking speed increased by 13 percent. DBS reduced the average hourly tremor score by 80 percent, but it did not affect the average involuntary movement score.

While previous theories suggested that DBS increased patients' "on-time," the findings suggested that the DBS improved patients' motor functioning without levodopa.

"The majority of studies that have looked at ways to improve the response to medications have been on the premise that what we want to do is extend the anti-Parkinson's action of each dose of drug," says Nutt. "That strategy generally leads to more [involuntary movements] and, over the long run, oftentimes leads to more drug toxicity."

Nutt says the findings may suggest that therapies should instead attempt to reduce the severity of the "off" periods.

Dr. Matthew Stern, director of the Parkinson's Disease and Movement Disorders Center at Pennsylvania Hospital, in Philadelphia, has found similar effects in Parkinson's patients with DBS. "It enables us, in fact, to reduce the dose of medication in many patients and that reduces some of the other complications," he says.

However, researchers still have more questions than answers about exactly how DBS works. Stern says one theory suggests that when a group of brain cells overfire due to a lack of dopamine, the firing of DBS shuts off those brain cells. He says researchers also are looking into whether DBS influences the progression of Parkinson's disease.

Nutt says DBS, which carries the risk of impaired speech, worsened confusion and stroke, also is expensive because of the cost of the equipment and surgery and because adjusting the device is time consuming.

He says it's appropriate for only a sub-group of patients with advanced Parkinson's disease that cannot be adequately controlled with drugs. But Stern says preliminary data suggests that some younger Parkinson's patients who get DBS require fewer resources and lead more functional lives.

What To Do

Find out more about Parkinson's disease from the National Institute of Neurological Disorders and Stroke, the Parkinson's Disease Foundation, the American Parkinson's Disease Association or the Awakenings Web site.

Here's how levodopa works in the brain, and here's a good drawing of where the subthalamic nucleus lies in the brain.

SOURCES: Interviews with John G. Nutt, M.D., professor, department of neurology, Oregon Health Sciences University, Portland, Ore.; Matthew B. Stern, M.D., professor, department of neurology, University of Pennsylvania, and director, Parkinson's Disease and Movement Disorders Center, Pennsylvania Hospital, Philadelphia, Penn.; Nov. 27, 2001, Neurology
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