HELSINKI — Neurosurgery for Parkinson’s disease has undergone a renaissance in the past decade and has become a standard treatment option for patients with advanced disease. Improvements in technique, expansion of targets, and a new understanding of parkinsonian pathophysiology have combined to make possible a wider array of surgical options than at any time in the past. Speaking at the 14th International Congress on Parkinson’s Disease, Andres Lozano, MD, Professor of Neurosurgery at the University of Toronto, explored the critical elements of implementing these advances.

BOUNDED BENEFITS

According to Dr. Lozano, “Surgery is very popular now because patients continue to be disabled despite the best available clinical therapy.” The three major reasons for choosing surgery are: to provide symptomatic benefit, to diminish the adverse effects of dopaminergic therapy, and to “prevent loss of opportunity for patients whose lives could be made fuller if some of the disability was diminished with surgery,” he said.

Surgery can be beneficial to many aspects of Parkinson’s disease, improving “levodopa-induced dyskinesias and tremor on the order of 80% or 90%,” while rigidity and akinesia can be improved by roughly 60%. Gait and postural abnormalities respond to a smaller extent.

But not all patients may benefit from surgery. “What are the top three predictors of benefit from surgery?” Dr. Lozano asked. “Response to levodopa, response to levodopa, and response to levodopa. If the patient has symptoms that do not respond to levodopa—including balance difficulties, bladder problems, constipation, pain, sexual dysfunction, depression, seborrhea, and sleep disturbances—it is unlikely that those symptoms will benefit with surgery,” he added.

Because of this, Dr. Lozano employs a levodopa challenge test to predict the potential benefits. The patient receives a dose of levodopa one to one-and-a-half times the normal morning dose, given in the “off” state. The results of the test are informative not only for the neurologist but also for the patient and family, to help them develop a realistic expectation for the procedure. “I tell them that this is the best that you can possibly hope for with a surgical procedure. Whatever disability you have despite this levodopa test, this is what you will remain with.”

PROFILING PATIENTS

Age is an additional factor in patient selection. “Even when unrelated to the instance of higher levodopa-resistant symptoms, and even when unrelated to cognitive disturbances, age may be an independent variable,” Dr. Lozano suggested. Patients must also be physically, cognitively, and emotionally able to tolerate both the procedure, which may last eight to 10 hours, and the postoperative care.

Dr. Lozano said that only about one third of patients referred to his clinic actually end up having surgery. The primary reason for refusing a patient is an inadequate trial of medical therapy. “For patients on low doses of dopaminergic drugs who are not burdened by side effects, the answer is simply to increase the dosage of the drug,” he explained.

SURGICAL SELECTION

They also differ in the kinds and timing of risks each entails. “When you do a procedure involving a lesion,” Dr. Lozano pointed out, “the risk is taken up front and is immediate. As you create the lesion, you create the adverse effect.” On the other hand, “when you are doing deep brain stimulation, there is an immediate risk related to the surgical procedure, but then there is an ongoing risk which remains for the life of the device.” The implanted pulse generator can malfunction, the wires or leads can break, the overlying skin may erode, and there is the risk of infection from the implanted device. Most of these risks remain for the life of the device, he added. Costs and maintenance also differ. Lesion surgery is relatively less expensive and requires little maintenance, while both costs and ongoing maintenance are higher for deep brain stimulation.

These disadvantages notwithstanding, Dr. Lozano noted there is a strong shift toward deep brain stimulation surgery, with safety as a leading reason. “Parkinson’s is a bilateral disease, and bilateral lesions are just not considered to be terribly safe, whereas the margin of safety with deep brain stimulation appears to be better,” he said. Nonetheless, there are risks, and as more patients receive deep brain stimulation electrode implantation, some unforeseen risks are emerging. For instance, Dr. Lozano cited a recent case in which a patient suffered severe neurologic damage after receiving diathermy following dental surgery.

LOCATION, LOCATION, LOCATION

In contrast, both globus pallidus internus and subthalamic nucleus surgery address akinesia, rigidity, and gait disturbance, in addition to tremor and dyskinesias. For this reason, “the thalamus has just about been abandoned as a target for the treatment of Parkinson’s disease,” he said, “and so the front-runners now are the subthalamic nucleus and the globus pallidus internus.”

Currently, the subthalamic nucleus is the favored target. “There is relative inexperience with the pallidal target,” Dr. Lozano said, with some reports showing good responses and others not. Because of this, he said, “there is a lack of incentive for groups that are currently doing subthalamic nucleus surgery to consider other targets.”

The experimental evidence favoring one over the other is not yet strong. “We know that with the pallidal deep brain stimulation or subthalamic nucleus deep brain stimulation, the improvement in the Unified Parkinson’s Disease Rating Scale can be quite similar in the best hands,” Dr. Lozano acknowledged. A recent paper in the New England Journal of Medicine supports this conclusion. In this non-randomized comparative study, both patient groups showed about a doubling of “on” time at the expense of “off” time, with a similar reduction in dyskinesias. However, he cautioned against over-interpreting these or any other results. “I think that we are still in the early days,” he said, “and a direct comparison of these two targets is not yet available.”

The absence of such evidence means that the final choice will often involve strong consideration of the track record of the center performing the procedure. Dr. Lozano observed that variations in adverse effects are often the result not only of the location of the implanted electrode but also of different levels of experience with each procedure among clinical teams. This appears to be “very dependent on the center,” Dr. Lozano said, with some groups reporting more adverse effects from surgery to the subthalamic nucleus than to the globus pallidus internus, and other groups the opposite. In addition, “the neurology team has to be very experienced in dealing not only with stimulation but also with manipulating the drugs” as stimulation is increased, to carefully reduce the quantity of dopaminergic medications. “This can sometimes be complex,” he said, “and it requires some experience.”

NR

Return to table of contents