Careful Site Selection Required for Deep-Brain Stimulation Treatment in Patients With Parkinson's Disease: Presented at AD/PD

By Chris Berrie

PRAGUE, Czech Republic -- March 14, 2009 -- Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is as effective as DBS of the globus pallidus (GPi) for improvements of fine motor function in patients with idiopathic Parkinson's disease (PD) when they were on medication, researchers noted here at the 9th International Conference on Alzheimer's and Parkinson's Diseases (AD/PD). When off medication, however, these patients can experience greater long-term adverse events with STN stimulation, despite the fact that it reduces the levodopa dosing needed for symptom management.

DBS is an alternative therapy for patients with PD, and involves surgical implantation of an electronic device into the STN or the GPi, with stimulation at both sites being effective in reducing motor symptoms.

"Deep brain stimulation is typically done when pharmacologic remedies fail, and it is currently done at more of an advanced stage of disease," noted principal investigator Tracie Caller, MD, Dartmouth Hitchcock Medical Centre, Lebanon, New Hampshire, presenting a systematic review here on March 14.

With little known about which stimulation site produces better outcomes, Dr. Caller's analysis was designed to compare the efficacy and safety of DBS of the STN and the GPi for reducing fine-motor symptoms in patients with PD.

Dr. Caller and colleagues searched the MEDLINE database, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov Web site, and bibliographies and meeting abstracts for relevant studies for direct comparisons of STN and GPi stimulation. They needed to report Unified PD Rating Scale (UPDRS) scores at preoperative baseline levels and at a minimum follow-up of 6 weeks. An assessment of the data quality was carried out by 2 blinded, independent reviewers.

Thirteen reviewed studies were found to be eligible according to inclusion criteria. The combined patient numbers saw DBS in the STN for 282 patients and in the GPi for 140 patients. Mean baseline characteristics were as follows: age 50 to 64 years; disease duration 8 to 17 years; and UPDRS motor scores off medication of 40 to 64.

Mean reductions in off-medicine UPDRS motor scores for the STN and GPi subjects at trial follow-up were 47% and 36%, respectively. On medication, these benefits were lower, at 14% and 20%, with 36% and 5% of subjects, respectively, showing reductions in levodopa treatments during follow-up.

The mean difference in the UPDRS motor scores across these trials thus demonstrated a significant benefit when off medication in favour of DBS in the STN over the GPi (-8.75; 95% confidence interval [CI], -13.46 to -4.04; P < .0001), although this benefit was lost when patients were on medication (1.73; -2.71 to 6.17; P = .09).

The adverse effects related to these stimulation sites were significantly higher for stimulation in the STN (risk ratio, 4.27; 95% CI, 1.17-15.52; P = .03). As the severities of these adverse effects were reported differently across the studies, however, this significant difference might not provide an accurate reflection overall of which adverse events were truly clinically significant, the researchers concluded.

"We tend to prefer subthalamic nuclear stimulation right now, clinically, but I think that with the rate of adverse effects of stimulation we need to be a little more careful in selecting who we are applying this technique to," Dr. Caller indicated.

[Presentation title: Deep Brain Stimulation of the Subthalamic Nucleus Versus Globus Pallidus for Parkinson's Disease: A Systematic Review. Abstract P2-135]

Meg Farris / Eyewitness News

NEW ORLEANS – The tremors caused by Parkinson's Disease can be life changing. But in a recent study, doctors found that deep-brain stimulation works better than the best medicine at improving quality of life.

A local man told Eyewitness News how the treatment is working for him, and a local doctor talked all about the breakthrough treatments that are on the horizon.

Gene Falgoust's family and co-workers at the refinery noticed at times his finger or leg would shake. Then years ago, when he was 47 years old, came the medical diagnosis.

"Well I said it can't be happening to me, but in the long run, I just accepted it," he said.

For a while, the part of his brain that was dying from Parkinson's Disease was helped with medication, but then he needed something more.

So what happened when he had deep brain stimulation?

"I stopped shaking. I wasn't shaking as much. I still shake now and then but not as much as I used too," said Gene.

Ochsner Neurologist and Parkinson's specialist Dr. J. Rao brought Falgoust into surgery. And while Falgoust was completely awake, the doctor opened up his skull to expose a part of his brain. Then they found the area that was causing the shaking problems and implanted a wire into it.

"When we are in the operating room, we check it with the hand-held battery operated gizmo and make sure it stops. We don't get out of the operating room until we are absolutely sure we found the spot (in the brain) that will make it stop," Rao said.

The wire is connected to a device about the size of a pacemaker and is programmed to give Falgoust the exact stimulation that he needs.

You can see the impression of the wire running up Gene's neck, and the stimulators in his body. He had one side done the old way using a painful halo to keep his head still during surgery, but just recently he had the other side of the brain done in a newer, more comfortable way, with a tower-like device.

"The procedure was different the first time I had it done. I had to wear a halo and it was piercing my skull. It was really painful, but this time nothing, and you have to be awake for the surgery and I could hear the doctors talking," Gene explains.

And Dr. Rao can turn the device on and off from the outside of Gene's body. You can see what happens when Gene's deep brain stimulator is off: he shakes continuously. When it is on, his hands are still.

"I'd always be embarrassed when I'd go out in public. You know everybody in Vacherie, it's a little town, but everybody in Vacherie prayed for me.”

But now his life has changed.

"I can write my name, I can do almost anything I want to now, he says.

Even dress himself.

"Yeah, well my wife had to help me at times. Now I do it all on my own," he adds.

The makers of the stimulator say not everyone is a candidate for it, but for people who are, you can instantly see the difference it makes in their lives. And while this is not brand new technology, Rao said in the next 10 years this will lead to major new changes.

"This is an enormously exciting time to be doing that," Rao said.

A nanochip alone will be implanted in the brain to fix the symptoms. It's already been done in animals. A gene will be introduced into the body to make the dopamine that the dying part of the brain can no longer make.

Growth factors, a protein that allows the dying cells to survive, could be available.

And your own stem cells could be made to go repair the damaged ones in the brain.

Rao says with the aging baby boomers, this technology could not come at a better time.

"The incidence in Parkinson's Disease is going to increase by 40-70 percent in Louisiana in the next 10 years," Dr. Rao cautions.

So for people such as Gene, the hope is as his disease gets worse, scientists will give him the opportunity to live even better.

One and a half million American's have Parkinson's, with 60,000 new cases diagnosed each year.

Women who count more years between their first period and menopause have a lower risk of developing Parkinson's disease, new research indicates.

The findings, which will be presented at the American Academy of Neurology's 61st annual meeting in Seattle in April, suggest that longer exposure to the body's own hormones may help protect brain cells affected by Parkinson's disease, says study author Rachel Saunders-Pullman, of Albert Einstein College of Medicine in the Bronx and Beth Israel Medical Center in New York and a member of the American Academy of Neurology.

Parkinson's is a nervous system disorder that occurs when special brain cells that make dopamine, a chemical messenger in the brain, die or become impaired. It leads to trembling and movement problems.

In the study, the researchers analyzed the medical records of 74,000 women who experienced natural menopause and about 7,800 women who went through surgical menopause. Among women with natural menopause, those who had a fertile lifespan of more than 39 years had about a 25-percent lower risk of developing Parkinson's than women with a fertile lifespan of less than 33 years.

Women who had menopause from surgery had almost twice the risk of developing the disease if they had previously taken hormone therapy and stopped than if they had never taken hormone therapy. Taking hormones did not have any effect on natural menopause women.

Author Saunders-Pullman says more research is required to understand why women with four or more pregnancies are at increased risk.

"This study does not support a role for treatment with hormone therapy in preventing Parkinson's, but there are still many unanswered questions," she says.

--By Mary Brophy Marcus, USA TODAY