Stereotactic Surgery for Parkinson's Disease
Dr. Ali Samii, UW Dep. Of Neurology
Co-Director APDA Information & Referral Service
Limitations of drug treatments for Parkinson's disease
Parkinson's disease (PD) is a progressive brain condition that impairs mobility. In early disease, tremor, rigidity and slowness of movement which are the cardinal features of PD, respond well to antiparkinson medications. However, with disease progression, drug dosages are increased and drug-induced side effects and fluctuations of mobility (motor fluctuations) occur more frequently. These motor fluctuations are usually characterized by end-of-dose wearing off and dyskinesias. End-of-dose wearing off is the decline in mobility that occurs a few hours after a dose of an antiparkinson medication. With disease progression, the duration of benefit from each dose becomes shorter and the wearing off phenomenon occurs earlier after each dose. Dyskinesia is the abnormal involuntary movement caused by medications in PD. It resembles exaggerated fidgetiness. These motor fluctuations and limitations of drug therapy have led to the resurgence of brain surgery for PD in the 1990s after 2 decades of dormancy.
History of stereotactic surgery for Parkinson's disease
In 1952, Cooper (a neurosurgeon) accidentally discovered that the ligation of a small vessel in the brain called the anterior choroidal artery led to improved tremor in parkinsonism. In the ensuing years, a variety of targets deep in the brain were "destroyed" to duplicate the results obtained by the ligation of that small vessel. Stereotactic brain surgery, which means targeted brain surgery using sophisticated 3-dimentional head frames, became more widely used. Localized heating (burning tissue), freezing, and inserting procaine oil were used to destroy small areas of brain tissue (making a lesion) to help PD symptoms as well as tremor unrelated to PD. In 1960, Svennilson and Leksell of Sweden reported their results of pallidotomy (making a lesion in the pallidum) on more than 80 PD patients. The pallidum is one of the deep brain nuclei that is "overactive" in PD and lesioning it seemed to help PD symptoms.
In the 1960s and 1970s with the development of levodopa, surgery for PD was abandoned. However, it was soon discovered that levodopa itself had many side effects, including abnormal involuntary movements called dyskinesia. When other drugs such as bromocriptine and pergolide were developed in the 1970s and 1980s, they seemed to help Parkinson symptoms, with less dyskinesia, but they were found to be less potent than levodopa. In addition, these new drugs had side effects of their own. Therefore, there was a resurgence of pallidotomy in the late 1980s. In 1992, Laitinen, another Swedish neurosurgeon, reported improvements in PD symptoms with pallidotomy, including a reduction in levodopa induced dyskinesia. This report revived stereotactic neurosurgery for PD after 30 years of dormancy.
Ablative surgery versus deep brain stimulation
Ablative surgery is the term used to describe the type of surgery where a small region of the brain is actually destroyed by heating or freezing. "Lesion" is a generic term that means an abnormality or loss of function of a tissue in th body. In PD surgery, the term "lesion" is used for the part of the brain intentionally destroyed by surgery. The suffix "-otomy" which follows the name of the target implies ablative surgery in that target. For example, thalamotomy is the name of the surgery where a lesion is made in the thalamus. Pallidotomy refers to tissue destruction in the pallidum, and subthalamotomy is a lesion in the subthalamic nucleus.
Deep brain stimulation (DBS) surgery is a procedure where an electrode is placed deep in the brain with its tip in the specific target of choice. The electrode delivers an electrical current at high frequency to the target tissue. Although the exact mechanism of action is not well understood, it is believed that the high frequency stimulation inhibits the target, hence "mimicking a lesion". In essence DBS has the same effect as ablative surgery, except that it is adjustable and reversible. With a lesion, the damage to the issue is permanent and so are the side effects from the lesion. With DBS, the effects of stimulation are reversed when the stimulation is turned off. This impermanency of stimulation-related adverse effects provides an advantage over ablative surgery.
Different targets for stereotactic brain surgery
The thalamus has been the target of choice for tremor for a number of decades. Thalamotomies and thalamic DBS have been performed for a number of years to relieve essential and parkinsonian tremor. Unilateral (one side only) thalamic DBS is now the preferred surgery for essential tremor. It helps relieve hand tremor on the side opposite the brain surgery. Bilateral (both sides of the brain) thalamic DBS is risker with a higher incidence of adverse effects on speech, memory, and balance. Therefore, thalamic DBS for tremor is usually not done bilaterally.
The pallidum is a popular target for PD surgery. The ablative pallidal surgery (pallidotomy) became quite popular in the early to mid-1990s after 30 years of dormancy. Unilateral pallidotomy helps improved tremor and dyskinesia on the side of the body opposite the brain surgery. It was soon discovered that bilateral pallidotomy can cause serious irreversible side effects with deterioration in speech, voice volume, and cognition. Pallidal DBS began to replace pallidotomy with fewer adverse effects when performed bilaterally. Bilateral pallidal DBS helps many symptoms of PD, but does not allow a reduction in anti-PD medication dosages.
The subthalamic nucleus is now a more popular target for DBS surgery in PD. Subthalamotomies are not performed in the U.S. (because of irreversible adverse effects), but they are done in many other parts of the world. Bilateral subthalamic nucleus DBS is now the most commonly performed surgery for PD. It helps many symptoms of PD and allows a significant reduction in the dosages of anti-PD medication dosages (usually by about 30%). The ability to reduce medication requirements has led some experts to suggest that bilateral subthalamic nucleus DBS is superior to bilateral pallidal DBS. However, the argument over the preferred target continues. At the University of Washington and Harborview Medical Centers, we believe that medication reduction is an important advantage, especially in patients who have side effects from their medications. Therefore, we are performing bilateral subthalamic nucleus DBS in or PD patients. First, surgery for the side more affected by PD is performed, and the surgery on the other side is done approximately 3 months later.
Criteria for patient selection
Choosing the right patient is extremely important in preparation for surgery in PD. It can make a significant difference in the outcome of the surgery. Patients with more advance PD whose symptoms respond to anti-PD medications but who are having side effects from these medications are ideal candidates. These patients typically have severe fluctuations in their symptoms throughout the day. In addition, they frequently have dyskinesias, which can be very disabling. The doses of their medications cannot be increased because of side effects. The patient should be no older than 80 years old, healthy without other serious illnesses, and independently ambulatory (able to walk alone). The patient should have normal cognition with intact language, thinking, and memory function. If depression or hallucinations are present, they should be mild and adequately treated. Extensive neuropsychological and movement testing is done before the surgery and repeated between the 2 surgeries and at frequent intervals after the second surgery. Theses repeated clinic and hospital visits demand a great deal of commitment from the patient and family members, so motivation is crucial. In a given PD patient population followed at a tertiary academic care center, only 5-10% of PD may be candidates for this type of surgery.
Risks of surgery and stimulation
Stereotactic surgery for PD is meant to work as adjunct therapy together with medications for relief of PD symptoms. It is meant to help reduce the duration of so called "off" periods which are periods during the wakeful hours when the medication is not working as well. The bilateral subthalamic nucleus DBS surgery should also help reduce medication dosages. However, these operations do not reverse the disease process, nor do they slow down the rate of progression of the disease at the cellular level. They are not curative and expectations from the surgery should be realistic. Serious adverse effects from the surgery include bleeding within the brain causing a stroke-like paralysis, speech or visual impairment, coma, and even death. Infections and seizures may occur. These serious side effects can take place 2-10% of the time. There also side effects related to the stimulation which are less serious than the surgical side effects. These stimulation-related adverse effects include intermittent numbness and tingling, worsening dyskinesias, mood and cognitive disturbances.