Surgery for Parkinson's

Summarized by Robert W. Griffith, MD
November 23, 2000 (Reviewed: February 16, 2003)

Introduction

Many people with Parkinson's disease have inadequate symptomatic relief with medical management, or have side effects from their medication that are themselves quite disabling. Not surprisingly, interest in the possibilities of long-lasting relief offered by various surgical approaches has re-emerged in recent years.

Ablative treatments (pallidotomy and thalamotomy) were introduced as treatments in the 1940s and 1950s. Then, in the 1960s, the introduction of L-dopa reduced the role of surgery. However, L-dopa did not prevent disease progression, and the duration of it's beneficial effect was found to lessen over time ("wearing-off") or fluctuate during the day (the "on-off" phenomenon).

Progress has since been made in developing new medicinal approaches - the combination of L-dopa with carbidopa, sustained release preparations, dopamine agonists, and most recently by decreasing the breakdown of L-dopa with catechol-o-methyltransferase (COMT) antagonists. At the same time, however, progress has also been made in the use of different surgical approaches, which have recently been reviewed by Dr Kenneth Follett of the University of Iowa.

The surgery involved

In Parkinson's disease, increased neuronal activity in the subthalamic nucleus causes overactivity in the medial globus pallidus and the substantia nigra. Excess activity in these two centers leads to reduced thalamic and brainstem activity, as well as reduced thalamocortical activity. Treatments aimed at reducing the overactivity of the globus pallidus or increasing thalamic activity are logically directed at restoring normal levels of functioning. If tremor predominates, the thalamus may be targeted for ablation or electrical stimulation (deep brain stimulation, DBS), but one of these procedures directed at the pallidum or substantia nigra is likely to provide greater overall improvement.

The candidates for surgery are those with idiopathic Parkinson's disease who respond to L-dopa to some extent, but have disabling symptoms, either from their disease or their medication. They should not have neuropsychological dysfunction (e.g. dementia), or any serious medical conditions.

Stereotactic surgery is usually done under local anesthesia, using coordinates obtained from a brain scan (CT or MRI). Proper localization of the target is confirmed by responses to focal electrical stimulation, which produces motor and sensory responses that are assessed when the patient is awake.

Ablative procedures

Usually, a radiofrequency generator produces a thermal lesion several millimeters in diameter. Some centers use cryosurgical or radiosurgery techniques.

Unilateral pallidotomy will improve tremor, rigidity, and bradykinesia in most patients. L-dopa-induced dyskinesia will be significantly improved, also. Most benefits are seen on the opposite side of the body to that of the surgery, with good control of dyskinesia and tremor for at least 3 years. After this time, other early benefits have usually disappeared, and activities of daily living continue to worsen.¹In some patients, bilateral ablation may be undertaken at the outset, while others may undergo a second ablation on the other side at a later date.

Serious complications are seen in 2-8% of cases of unilateral pallidotomy. Spread of the lesion beyond the target area may lead to visual impairment, facial paresis, hemiparesis, and changes in speech, voice volume, and memory. Bilateral pallidotomy is associated with an increased risk of complications, in particular speech dysfunction, drooling, balance and memory.

Deep brain stimulation (DBS)

DBS represents an advance over structural ablation. The lesions are "functional" i.e. the effects may be adjustable and reversible, and therefore safer and more effective in the long term. Thalamic stimulation with an implantable DBS system has largely supplanted thalamotomy for intractable tremor in many centers. The globus pallidus is also an established target for DSB. However, DBS of the subthalamic nucleus and substantia nigra are experimental procedures currently under evaluation.

A permanent stimulation electrode is passed through a guide cannula to the target site. A pulse generator (like a cardiac pacemaker) is implanted under the skin below the clavicle, and connected to the stimulating electrode subcutaneously. This part of the procedure is usually done under general anesthesia. The amplitude, pulse width, frequency and pattern of stimulation is adjusted by telemetry. The system can then be activated by the patient, when necessary, using a small hand-held magnet.

Bilateral DBS is particularly suited for subjects with bilateral symptoms, where bilateral pallidotomy has a fairly high rate of side effects. Reprogramming the system can usually eliminate any adverse effects of stimulation. The procedure carries a greater cost than ablation treatment.

Unilateral and bilateral DBS of the pallidum are as effective as the corresponding ablative procedures - rigidity, tremor, bradykinesia, gait, the amount of "on" time, L-dopa dyskinesia and Activities of Daily Living scores are all improved. Contralateral DBS of the pallidum can be useful in patients who have had a previous unilateral pallidotomy and need treatment for the other side.

DBS of the substantia nigra has proved to be effective in smaller series of cases, with results roughly equivalent to that of stimulation of the pallidum, except for reducing L-dopa dyskinesia; however, it's effectiveness usually allows the L-dopa dose to be reduced sufficiently so that this side effect can be avoided.

Future approaches

Transplantation of adrenal medullary tissue was first reported to improve symptoms of Parkinson's disease in 1987. Since then, other tissues have been used, including peripheral nerve and fetal mesencephalic tissue. In general, the symptomatic improvements obtained are more modest than those achieved by ablation or DBS. This approach must be regarded as still being in the developmental stage.

While surgical approaches to the treatment of Parkinson's disease continue to be developed, new medications are on the horizon. Doubtless control of the distressing symptoms will improve in the next few years. Beyond that, we can look to gene therapy as a way to impact the disease process at an earlier stage, with possibly much greater long-last efficacy.

Source

• The surgical treatment of Parkinson's disease. KA. Follett, Annu Rev Med, 2000, vol. 51, pp. 135--147

Footnotes
1. Long term outcome of unilateral pallidotomy: follow-up of 15 patients for 3 years. PK Pal, A Samii, A Kishore, Am J Neurol Neurosurg Psychiatry., 2000, vol. 69, pp. 337--344

Related Links
Syllabus: Management of Parkinson's disease

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