Parkinson's Disease

UF Doctors Test Targets For Parkinson Surgery
Main Category: Parkinson's Disease
Also Included In: Clinical Trials / Drug Trials;  Medical Devices / 
Diagnostics;  Regulatory Affairs / Drug Approvals
Article Date: 16 Mar 2009 - 2:00 PDT

Doctors may be able to tailor a specialized form of brain surgery to more 
closely match the needs of Parkinson patients, according to results from the 
first large-scale effort to compare the two current target areas of deep 
brain stimulation surgery, or DBS.

Called the COMPARE Trial, the National Institutes of Health-funded study 
conducted at the University of Florida evaluated 45 patients for mood and 
cognitive changes related to DBS.

UF investigators found that DBS in either brain target effectively treated 
motor symptoms such as tremors, stiffness and slowness.

However, DBS also produced unique effects depending on the target location, 
especially in patients' moods and mental sharpness.

The discoveries, in Annals of Neurology, may have an impact on the selection 
of DBS patients, especially those with pre-existing memory, cognitive or 
mood disabilities.

"Both targets are FDA-approved and provide excellent outcomes for motor 
function in Parkinson patients," said Michael S. Okun, M.D., the principal 
investigator of the study and a co-director of the Movement Disorders Center 
at UF's McKnight Brain Institute. "But there were differences in cognitive 
function and verbal fluency seven months after the surgery, and that is 
something that should be considered when trying to tailor therapy to an 
individual patient's condition."

DBS received Food and Drug Administration approval in 2002 as a therapy for 
movement-related problems associated with essential tremor and Parkinson's 
disease. It uses a medical device surgically implanted in a patient's brain 
and connected to a power pack in the shoulder region. DBS delivers 
electrical pulses to targeted areas of the brain via very thin wires, known 
as "leads." Each lead ends with four distinct electrical "contacts."

Currently, in almost all cases worldwide, the leads are implanted in a brain 
region known as the subthalamic nucleus. But the nearby globus pallidus 
interna, or GPi, may again emerge as a viable target, especially for 
patients with mood and cognitive issues, researchers say.

Forty-five volunteers with moderate to advanced Parkinson's disease 
completed the prospective, randomized study. Twenty-three received leads to 
the GPi and 22 to the subthalamic nucleus.

Before surgery, scientists at UF's Cognitive Neuroscience Laboratory 
evaluated the patients' verbal fluency, memory, attention and cognitive 
processing. Patients were retested about seven months later during four 
conditions - with stimulation at the optimal contact point on the lead as 
determined during previous programming sessions, with stimulation at contact 
points adjacent to the optimal one, and with stimulation turned off. 
Examiners and patients were blind to the conditions as well as to the brain 
target.

Generally, the target choice produced no major differences in motor 
function, mood or cognition in the patients. However, patients whose leads 
were implanted in the subthalamic nucleus, the most common surgery target, 
did have increased problems with verbal fluency and mood - and they tended 
to be more angry and irritable.

"We think it will be important to tailor the therapy to the patient," said 
Kelly D. Foote, M.D., an associate professor of neurosurgery at the College 
of Medicine and a co-director of the UF Movement Disorders Center. 
"Targeting the traditional location - the subthalamic nucleus - might be 
better for someone who is younger and healthier. But for someone who is 
older with memory problems, or perhaps in the early stages of dementia, it 
would be important to consider the alternative."

The traditional target does have unique advantages, Foote said. It seems to 
be more effective at reducing a patient's medications, which may lead to an 
improved quality of life and cost savings. In addition, because it is 
relatively smaller - about a third the size of a pea - less electricity was 
required to stimulate this area, which is an important consideration because 
more surgery is required to replace DBS batteries.

More study will be necessary to determine whether DBS target choice can be 
tailored to meet individual patient needs. However, in considering the 
surgery, potential patients need to weigh the benefits of DBS against risks 
such as mild cognitive decline.

"It is unclear whether these mild cognitive changes are clinically 
significant in terms of the patient's everyday life," said Dawn Bowers, 
Ph.D., a professor in the department of clinical and health psychology in 
the College of Public Health and Health Professions and the director of the 
Cognitive Neuroscience Laboratory where the patients were assessed. "Though 
important, they pale in comparison to the tremendous boost these patients 
receive in motor behavior."

In the meantime, scientists say uses for DBS technology will continue to 
move beyond the movements disorders field.

"It is vitally important that we take the opportunities afforded to us by 
deep brain stimulation technology to better understand what underpins mood 
and cognitive circuitry in the brain," said Okun, who is also an associate 
professor of neurology and neurosurgery at the UF College of Medicine and 
the national medical director of the National Parkinson Foundation. "What we 
have learned from Parkinson's disease we are now taking into other areas, 
and as we unlock the circuitry, we can apply new technologies to ultimately 
improve quality of life."

Source: John Pastor
University of Florida

Rayilyn Brown
Director AZNPF
Arizona Chapter National Parkinson Foundation
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