Deep Brain Stimulation for Parkinson's Disease

DEEP BRAIN STIMULATION FOR PARKINSON'S DISEASE

by Mike Rezak, MD, PhD

For some patients, the thought of undergoing a surgical procedure to treat Parkinson's disease can be overwhelming or even considered an extreme
measure, especially if motor function is adequate (albeit far from optimal) i.e., good enough to "get by." Furthermore, since by its very nature, Parkinson's disease is a slowly progressive disease, and individuals tend to "adapt" to worsening symptoms and the development of dyskinesias and motor fluctuations and may dismiss the option of neurosurgical intervention that can be so dramatically effective for them. Deep brain stimulation (DBS) can significantly benefit tremor, bradykinesia, rigidity, dyskinesias, and motor fluctuations. The improvement in quality "on" time ("on" without troublesome dyskinesias) is dramatically improved. In a recent study, improvement in quality "on time" obtained from DBS versus a best medically managed group was compared. The DBS group obtained 4.6 hours versus zero hours of benefit in the best medically managed group. DBS for Parkinson's disease was FDA approved in 2000.

The decision to proceed to neurosurgical intervention in PD is determined by the presence of symptoms that can no longer be adequately controlled by
pharmacologic means. It is generally agreed that earlier intervention, in the middle stages of PD, results in the most robust symptomatic response. The
response obtained from the DBS parallels the best response obtained from l-dopa,but without side effects (especially psychiatric and motor complications) and often with much less medicine. Medications can usually be reduced by 30% to 50% and sometimes even more. DBS is particularly beneficial in treating dyskinesias and motor fluctuations, but also rigidity and bradykinesia. It is generally recognized that younger patients tend to have a more dramatic benefit compared to older patients.

The anatomy, physiology and pharmacology of the normal organization of the brain circuit subserving smooth voluntary movement, the basal ganglia, is now well understood. This understanding has allowed us to intervene and reset the abnormal signals that results from the loss of dopamine neurons in the substantia nigra. The substantia nigra normally provides input to the basal ganglia. When this dopaminergic input to the basal ganglia is lost, excessive inhibitory activity is conveyed to the rest of the motor system ultimately resulting in the classic features of PD including bradykinesia, rigidity, tremor and postural reflex (balance) impairment. For the carefully selected PD patient, the result of inserting a deep brain stimulator into the subthalamic nucleus (STN) or internal segment of the globus pallidus (GPi) can be a dramatic improvement in previously difficult to manage symptoms. The STN and GPi are considered the final output structures of the basal ganglia to the rest of the motor system and thus intervening in these sites is critical to obtaining symptomatic improvement.

Factors related to good outcomes with DBS for PD include:

1. Appropriate patient selection (i.e. choosing the correct candidate-see below).
2. DBS electrodes must be optimally placed for maximal benefit . This requires microelectrode mapping during surgery by a neurophysiologist to assure precise localization of the brain target.
3. An experienced DBS team . There is a learning curve in successfully implanting the DBS and one should seek a center that has implanted many patients.
4. An experienced DBS programmer. Once implanted, the device will be optimally programmed to alleviate the target symptoms.
5. Intervention at earlier stages of PD. One should consider DBS when increasing doses of medications are required to control motor symptoms and/or when motor fluctuations and dyskinesias are present.

Patient selection criteria:

1. Absence of significant cognitive problems. This is often determined by formal neuropsychological testing which the neurologist can arrange. Significant cognitive impairment will exclude a patient from undergoing the DBS procedure.
2. Symptom responsiveness to levodopa which reinforces the diagnosis of idiopathic PD. DBS is not beneficial in the other forms of Parkinsonism which typically have little or no response to PD medicines. The symptoms that respond well to levodopa will respond well to DBS.
3. Motor fluctuations and troublesome dyskinesias. DBS is excellent at eliminating these troublesome complications from levodopa.
4.Patients with idiopathic PD, but who are intolerant to PD meds. This small subset of patients will typically respond well to DBS.
5. Significant medical illnesses. All patients must obtain clearance from their primary medical physicians before undergoing DBS surgery. A significant medical problem may pose an increased risk of complications and might prevent surgery.
6. Symptoms unresponsive to l-dopa.

Gait and balance issues that do not respond to l-dopa will also not respond to DBS. Non-motor features of PD should also not be expected to respond to DBS.

Advantages of DBS:

1. Flexibility. Stimulation can be adjusted to control symptoms and changes in symptoms over time. Benefits have been shown to last for years.
2. Reversibility. There is no significant destruction of brain tissue with DBS and the device can be removed at any time with no consequences.
3. Medications can be reduced. Medications often can be significantly reduced.

Disadvantages of DBS:

1. Hemorrhage/stroke . There is a small (average 2%) but definite risk.
2. Infection. This risk is relatively small, but variable and prophylactic antibiotics are typically used to reduce this possibility.
3.Cosmetics . There are scars on the skull where the burr hole was drilled (usually covered by hair) and small scars on the scalp. There is also a lump under the clavicle where the generator is placed and some scars under the
clavicle.
3. Hardware considerations. As with any mechanical device, malfunctions may rarely occur. These are typically easily correctable. Battery life is usually 3-5 years depending on individual patient requirements. The battery is replaced in an outpatient surgical setting. Longer life batteries are being developed.
4. Miscellaneous issues . Patients with DBS should not have diathermy (therapeutic ultrasound). MRI of the brain and neck are allowed, but contraindicated for imaging of other body parts. There are no problems with x-rays or CAT scans. When an MRI is to be performed, the DBS must first be deprogrammed.

Deep brain stimulation for Parkinson's disease should always be considered for those individuals whose symptoms are progressing and becoming more difficult to manage. An experienced DBS center will be able to assess the potential for benefit from this procedure for any individual based on the criteria stated above. This powerful treatment option reflects the advances in knowledge that has emerged from on-going research efforts into understanding the many aspects of Parkinson's disease.

Dr. Rezak is the Medical Director of the APDA National Young Onset Center as well as the Director of the Movement Disorders Center and Co-Director of the Deep Brain Stimulation Program of the Neurosciences Institute at Central DuPage Hospital in Winfield, IL. Dr. Rezak is also on the Speaker's Bureau for Allergan, Novartis, Medtronic, Teva, and GlaxoSmithKline.

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