Parkinson's Disease (PD)

Parkinson's Disease

Surgery

Brain surgery is an option for advanced PD patients whose symptoms can no longer be adequately managed pharmacologically. The best surgical candidate is someone who responds well to dopaminergic therapy but has motor complications (off periods and dyskinesias) that are limiting factors, and who is otherwise healthy and a good surgical risk. Advanced age is not necessarily a barrier to surgery; however, impaired cognition and brain atrophy increase surgical risk and decrease the likelihood of an optimal outcome. Depending on the patient, procedure, and skill of the operating team, cognition may be mildly impaired or largely unaffected. The most commonly reported adverse neuropsychiatric effects are reduced executive function and language impairments.

Types of Surgery
There are two surgical procedures—lesioning and deep brain stimulation—and three target locations in PD surgery: thalamus, globus pallidum internus (GPi), and subthalamic nucleus (STN). Deep brain stimulation (DBS) uses implanted electrodes to create a functional thalamotomy, pallidotomy or subthalamotomy. Lesion procedures (pallidotomy, thalamotomy) deliver radio-frequency energy to heat and ablate a pea-sized region within the target.

Cell transplants, gene therapy, and neurotrophic factor delivery remain experimental procedures for the treatment of PD.

Deep Brain Stimulation (DBS)
DBS uses a programmable stimulator implanted in the chest wall, connected by subcutaneous leads to implanted, bipolar electrodes in the brain. The stimulator can be turned on and off by a magnet. Batteries can be replaced as needed, generally after 5 years. The high-frequency stimulation simulates a lesion, although the exact mechanism is not known.

There are a large number of methodological issues that affect the efficacy of the procedure, including:

The target chosen
The ability to accurately locate the electrode in the target
The variables of stimulation, and
Post-operative changes in medication.

Adjusting the stimulation parameters after electrode implantation is a major time commitment on the part of the neurological team and patient.

Thalamic DBS
Like thalamotomy, thalamic DBS is primarily effective against tremor. Bilateral procedures are possible, but with a higher risk of adverse effects. Compared to thalamotomy, thalamic DBS has less morbidity.

GPi DBS
Effects of GPi DBS tend to mimic those of pallidotomy. Dyskinesia improvement is a major effect, along with some improvement in the cardinal motor signs of PD, primarily in the off-medication state. Bilateral DBS is better tolerated than bilateral pallidotomy.

Subthalamic DBS
The subthalamic nucleus (STN) has become a major target for DBS, with many teams considering it the target of choice for control of PD. It leads to improvement of all cardinal features of PD, with improvement of motor scores of 40% to 60% in the off condition, and 10% in the on condition. Levodopa dosage reduction is typically 30%, with resulting improvement in dyskinesias. Bilateral procedures appear to be superior to unilateral, with only a slightly increased risk of complications.

As DBS has become more common, rare but serious neuropsychiatric adverse events have been increasingly reported. Onset or worsening of depression occurs post-operatively in a small percentage of patients, often in those who prospectively are at increased risk for neuropsychiatric complications. Suicide, a well-known risk in depressed patients, has been reported in a small number of patients. Pre-operative neuropsychiatric evaluation is essential and post-operative follow-up is also a critical part of patient care.

Pallidotomy
Until the late 1990s, pallidotomy was the most common type of PD surgery (DBS is now more commonly performed). The target is located using microelectrode stimulation, with care taken to avoid the nearby optic tract. A microelectrode is then used to confirm placement, based on the globus pallidum internus (GPi) firing pattern; therefore, the precise location of the GPi is identified by the characteristic electrical patterns of the GPi. Radiofrequency lesioning is then performed. Effects are apparent almost immediately.

Depending on the center and the study, improvements from pallidotomy range from 70% to 90% for dyskinesias and dystonia, and 25% to 50% for tremor, rigidity, bradykinesia, and gait. Dyskinesia improvement is based partly on the reduction in levodopa dose made possible by the surgery. Improvements are primarily contralateral to the lesioned side and observed more while off medication than while on medication. Bilateral surgery is possible and improves dyskinesias further, but greatly increases the risk for worsening cognitive and bulbar effects, and is rarely performed today.

Adverse effects of pallidotomy may include:

Hemorrhage (2% to 6%)
Weakness (2% to 8%)
Visual field deficit (0% to 12%)
Confusion (0% to 8%)
Weight gain (50% to 70%)

Thalamotomy
Thalamotomy is primarily effective for tremor, and is therefore indicated mainly in patients for whom tremor is the only disabling symptom. Bilateral procedures are poorly tolerated because of increased complication risks, especially visual field deficits and language impairment. The procedure has largely been replaced by thalamic DBS in PD patients in the United States (but remains a useful treatment for medically intractable essential tremor).