March 26, 1999

VUMC to lead national study of Parkinson’s treatment

VUMC to lead national study of Parkinson's treatment

Vanderbilt University Medical Center is taking on a leadership role in the study of deep brain stimulation to treat Parkinson's disease with the formation of the Deep Brain Stimulation Study Group.

The treatment involves using a thalamic stimulator to alleviate some of the tremors associated with drug-resistant Parkinson's disease. The device – first implanted into a patient at VUMC in 1995 – is placed under the skin in the upper chest and a wire carrying electrical impulses travels under the skin to the top of the head and then passes through the skull.

Although this device was effective in alleviating some tremors, a new target inside the brain was recently identified that may help ease some of the other debilitating symptoms associated with Parkinson's disease, such as stiffness, difficulty walking and loss of balance.

To study the device's effectiveness, Vanderbilt is forming the study group, which includes investigators from the National Institutes of Health, the University of Kansas and Emory, Baylor and Ohio State universities.

"The new target is called the sub-thalamic nucleus, which is a very small area on both sides of the brain that becomes overactive as Parkinson's disease progresses," said Dr. P. David Charles, assistant professor of Neurology and head of the new Deep Brain Stimulation Study Group.

Assistance in finding the source of many of Parkinson's disease's symptoms came from a strange source – illegal drug users. Home-brewed heroin occasionally resulted in the creation of a substance called methyl-phenyl-tetrahydropyridine (MPTP). Injection of the MPTP-laced drugs was found to cause severe, irreversible Parkinsonism by killing an area of the brain called the substantia nigra.

Today, it is known that the Parkinson's disease in older adults is caused by the progressive death of neurons in the substancia nigra.

"We know now that the cells in the subthalamic nucleus are regulated by these substancia nigra cells. So when they die off then the subthalamic nucleus becomes wildly overactive, which causes many of the symptoms of Parkinson's disease," said Charles.

To verify that the subthalamic nucleus was indeed the site of the tremors, the researchers placed a needle into the subthalamic nucleus of a patient with a tremor and recorded the activity of those brain cells.

"What they found when they played the noise over the speaker in the operating room was that they could hear the neurons firing at a very high rate," said Charles.

Once the lead for the subthalamic stimulator is in place, the device works by sending a small electrical signal that inhibits the overactive brain cells and ceases many of the symptoms.

"The lead that goes into the brain has four contact points at the end. So once you place it in the brain you can adjust the stimulation by a few millimeters without having to go back into surgery. You can also increase or decrease the voltage of the stimulation," said Charles.

The ability to adjust the voltage and the area of the brain that is being stimulated is very important. Equally important is the placement of the lead.

"Though the surgery is fairly straightforward, there are some special instruments that we use to listen to the brains cells to find the right area," said Dr. Peter E. Konrad, assistant professor of Neurological Surgery and the team's neurosurgeon.

"One of the challenges of the procedure is that this area of the brain tolerates no mistakes – any bleeding or missteps can be neurologically devastating," said Charles.

"Once the lead is positioned and the voltage tuned, the device works much like the drugs used to treat Parkinson's disease. It lessens the symptoms, but does not cure the disease."

The difference between the stimulator and the drugs is that there is no "down time" between doses of the drugs. The long-term effectiveness of the stimulator is, as yet, unknown.

"That is why we really need to do these clinical trials, and formation of a national group will speed discovery," Charles said.