Learn More About Research
Currently we are conducting multiple studies of investigational new medications added on to levodopa to determine if these investigational treatments improve symptoms. Clinical trials assess drugs are not yet approved by the FDA and by participating in these trials, individuals may obtain access to these investigational new medications. Learn more about risks and benefits of participation in clinical research.
Learn About Clinical Trials:
What are Clinical Trials?
How do they work?
What are the phases?
Why participate in Clinical Trials?
Who can qualify?
What else should be considered?
Deep Brain Stimulation Education
Surgical treatment for Parkinson’s disease is indicated for patients who have disabling motor complications despite maximal drug therapy. This includes disabling levodopa-induced dyskinesias, medication-refractory disabling tremor or marked motor fluctuations in which there is variation in mobility from extremely immobile to good functioning. Surgical treatment is very helpful to treat motor complications, but with the exception of improving tremor does not significantly improve the patient’s best response to levodopa. Effectively, surgery allows patients to function as they do during their best peak time on levodopa, with significant reduction in dyskinesia and marked reduction in motor fluctuations.
Preoperative response to levodopa is the best indicator of a patient’s response to surgical treatment. In general, patients who are good candidates for surgery have had Parkinson’s disease for five to ten years or more and have significant disability as a result of motor fluctuations, dyskinesias, or disabling tremor. They should not have significant cognitive impairment or dementia since surgery may, in fact, worsen this problem. Because of the risks of surgery, there should be a reasonable expectation of several years of life expectancy following surgery for the risk-benefit ratio to be reasonable. Even elderly patients who are in good general health and are cognitively well may be considered for surgery if they otherwise fulfill the criteria.
The preoperative evaluation and subsequent treatment of patients considered for surgical treatment includes a movement disorders specialist neurologist, neurosurgeon, neuropsychologist, and commonly a physiatrist or rehab specialist. The neurologist is responsible for the preoperative evaluation as well as the postoperative deep brain stimulation programming and ongoing clinical care. The neurosurgeon is responsible for the overall surgery and management of any surgical complications. Virtually all patients who are considered for surgical treatment for Parkinson’s disease should undergo detailed neuropsychological testing. The neuropsychologist advises on the patient’s candidacy for surgery based on his or her evaluation of the patient’s cognition and any potential mood issues. Many patients benefit from physical, occupational, and speech therapy postoperatively in combination with deep brain stimulation programming in order to optimize their benefit. A rehab physician can help to best coordinate this care.
There are two main surgical methods which are used routinely in clinical practice. Deep brain stimulation involves implanting an electrode in a target site and hooking this up to a pacemaker-like device to deliver an electric signal to that area of the brain. Lesioning surgery involves destroying the target site with a radiofrequency probe to abolish the abnormal signals coming from this dysfunctional region of the brain. In general, lesioning procedures are performed infrequently in the United States since the effect is permanent and cannot be adjusted after surgery. Deep brain stimulation allows for modification of both the beneficial and adverse effects after surgery by programming the pacemaker-like device. This may result in better effects and certainly results in fewer complications, especially when surgery is performed on both sides of the brain.
There are three main surgical sites for Parkinson’s disease treatment; the subthalamic nucleus, the globus pallidus and the thalamus. Surgery is most commonly performed in the subthalamic nucleus and the globus pallidus on either one side or both sides of the brain. In these locations, deep brain stimulation can significantly improve all the major motor features of Parkinson’s disease, including bradykinesia, rigidity, tremor, and, to a certain extent, gait. On the other hand, surgery in the thalamus improves only tremor. When surgery is performed on one side of the brain, the major benefit is seen on the opposite or contralateral side. For example, surgery on the left side of the brain predominantly results in improvement on the right side of the body. Some patients may require only surgery on one side of the brain whereas other patients may require bilateral surgery.
Deep brain stimulation involves implanting an electrode in the target region in order to alter the pattern of the abnormal cell firing. The electrode is connected to a pulse generator or pacemaker-like device which is implanted usually in the area below the collar bone. This is connected to the electrode by a cable tunneled underneath the skin of the neck and scalp. The surgical implantation of the electrode is most commonly performed with the patient awake to allow for continuous monitoring of effects of stimulation during the electrode implantation procedure. The remainder of the hardware including the pulse generator and connector cable is implanted under general anesthesia.
Setting the stimulation parameters of the pulse generator is usually referred to as deep brain stimulation programming. Programming is usually begun one or two weeks after surgery. The stimulation frequency, amplitude of stimulation, and other parameters can be altered in order to maximize benefit and minimize adverse effects. Typically, patients are repeatedly examined as different stimulation settings are tested. This process may require repeated evaluations over days or weeks. Usually by two to three months after surgery, the stimulation settings are optimized. While the stimulation settings are being adjusted, anti-Parkinson medication is usually altered and is commonly reduced, especially with subthalamic nucleus stimulation. There needs to be good cooperation and communication between the patient and neurologist in order to facilitate recognition of optimal stimulation settings to allow for avoidance of adverse effects. The pulse generator batteries last on average four to five years before needing replacement. Recently, a rechargeable pulse generator has become available which requires replacement only every nine years.
With unilateral globus pallidus or subthalamic nucleus deep brain stimulation, improvement in overall parkinsonism by approximately 30% is typical. If surgery is performed on both sides of the brain, patients improve on average 50% or 60% compared to his or her “off” state. Tremor, bradykinesia, and rigidity generally improve more than gait and balance. With the improvement of off-period parkinsonism, motor fluctuations are markedly improved. Either because of the direct suppressive effect on dyskinesias or because of a significant reduction in medication, dyskinesias are improved by 80 to 90%. As a result, patients commonly function near their best preoperative state all of the time but with significantly less dyskinesias. In clinical trials, patients undergoing bilateral subthalamic stimulation had an increase in “on” time by about six hours per day on average.
Unfortunately, surgical treatment of Parkinson’s disease does not stop disease progression and does not improve symptoms that are not improved at the peak effect of levodopa, with the exception of tremor. As a result, it is important to emphasize that the preoperative response to levodopa is highly predictive of the response to surgery. The best “on” state function is not improved after surgery. In addition, certain symptoms may actually be worsened by surgery including difficulties with balance, cognitive and psychiatric difficulties, dysphagia or swallowing difficulty, and slurred speech. The presence of any of these difficulties preoperatively should be carefully evaluated when making a decision about the appropriateness for surgery.
Like all surgical procedures, deep brain stimulation and lesioning have potential complications and risks. This risk of bleeding into the brain or hemorrhage is about 1 to 2% unilateral surgery and 2-4% for bilateral surgery. Because a mechanical device is implanted, there is a risk of infection of either the wounds or the device. This risk approaches 5 to 10% and is maximal in the first two or three months after surgery. Because patient movement results in stress on the hardware, this may fracture or erode through the skin. This may occur even many years after surgery. Some patients may experience transient confusion or hallucinations during and immediately after surgery. This is most apt to occur in patients who have some preoperative cognitive impairment. Usually this gradually resolves over one to two weeks after surgery. Weight gain averaging approximately 20 pounds is common after bilateral subthalamic nucleus deep brain stimulation. This may in part be due to a marked reduction in levodopa-induced dyskinesias.