"Brain surgery is not a new concept in treating Parkinson's patients," says Jorge Juncos, M.D., associate professor of neurology, Emory University School of Medicine and co-investigator of this study. "However, Cuban neurologists, neurophysiologists and neurosurgeons are taking one of these surgeries, which they've been performing since the mid-90s, to a new level and the results continue to be promising." Parkinson's disease is a progressive disorder of the central nervous system affecting over one million people in the United States.
Symptoms include tremor, slowness of movement and stiffness of muscles. The loss of nerve cells in an area of the brain called the substantia nigra creates an imbalance that disrupts normal movement. Although certain medications, such as levodopa or L-dopa, can reduce the symptoms, they do not slow the progressive deterioration in function of PD.
The surgical procedure used in this study involves going deep into the brain, to a region called the subthalamic nucleus, to destroy small clusters of nerve cells that contribute to the above motor symptoms. The subthalamic nucleus helps control movement on the opposite side of the body. Past research has shown that by removing (i.e. "lesioning") or disabling (i.e. electrically "jamming") this and other select areas in the brain improves motor function in patients with PD.
Three years ago at an ANA meeting, Cuban neuroscientists Lazaro Alvarez, M.D. and Raul Macias, M.D., presented material showing they could safely lesion the subthalamic nucleus on one side of the brain, called unilateral subthalamotomy, that could later be followed by a second procedure on the opposite side. Now these investigators have taken the procedure a step further by lesioning the subthlamic nuclei on both sides of the brain simultaneously, a so-called bilateral subthalamotomy. By reducing the number of surgical sessions from two to one, the doctors reasoned they could reduce patient discomfort and inconvenience, and perhaps lower the risk of the intervention itself.
In this pilot study, bilateral subthalamotomy was performed on 18 Parkinson's patients at the Centro Internacional de Restauracion Neurologica (CIREN) in Havana, Cuba. The participants were followed for 24 months after surgery. Dr. Juncos and Mahlon DeLong, M.D., professor and chair of Emory's Neurology Department, both traveled to Cuba on several occasions to evaluate the participants.
"Following surgery, we examined the participants in Cuba and evaluated their motor skills, stiffness and tremor while off their PD medications," says Dr. Juncos. "We also reviewed videotapes obtained before and after the surgery, as well as brain imaging studies."
Two years after their surgery, as a group, patients exhibited approximately a 50 percent improvement in motor symptoms and in drug-induced abnormal movements, compared to their scores before surgery. Patients also exhibited significant improvement in activities of daily living. Patients who also exhibited defects in mental ("frontal") information processing before surgery showed improvement in these defects after surgery. Although there were no serious permanent side effects from the surgery, three patients with large lesions developed severe abnormal involuntary movement (dyskinesias), imbalance and trouble speaking. These symptoms improved gradually over the next 3-6 months and the patients retained otherwise significant improvement in PD motor symptoms.
Another benefit of this surgery was an apparent 70 percent reduction in the doses of medication required to treat the patients' motor symptoms. The smaller doses of medications undoubtedly added to the benefits obtained from the surgery.
Dr. Juncos, speaking for the team, says, "the outcome of bilateral subthalamotomy is showing positive signs, both in sustained movement benefits and in the absence of cognitive, speech or balance side effects. These problems were known complications of previous attempts at using bilateral brain lesions that targeted other areas of the brain like the thalamus and globus pallidus. We are encouraged by the long-term efficacy and safety of this new approach after two years of follow-up." Dr. Juncos presented the findings of this recent study at the ANA on behalf of the Cuban neurosurgeons and other investigators. The Cuban doctors were not able to attend the conference because of recent hurricane damage to their island and difficulties obtaining U.S. visas.
"This collaboration has been and continues to be a great experience for researchers and patients alike," Dr. Juncos explains. "The Cuban doctors have given their international collaborators unfettered access to their patients, to imaging studies and all other clinical material. The data have been the subject of open scrutiny and authors outside of Cuba who have helped analyze much of it. We, at Emory, feel very fortunate to have been a part of this study and plan on expanding our relations in future studies with these researchers."
With these new results, researchers will now need to explore how bilateral subthalamotomy compares to deep-brain stimulation (DBS) of the subthalamus, a "pacemaker-like" approach recently approved by the U.S. Food and Drug Administration for the treatment of advanced PD. Because DBS required the use of two pacemakers (one for each side of the brain) and connecting wires, it is more costly than the lesioning procedures used in Cuba. Additional costs stem from the need to periodically adjust the settings of the pacemaker devices that drive the stimulators. "Assuming the safety and efficacy of these lesions performed in Cuba prove to be comparable to that of the better established DBS technique, future investigations will need to evaluate the benefits in relation to the costs of these procedures," says Dr. Juncos.
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