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Deep brain stimulation

Parkinson's disease

Parkinson's disease (PD) is a neurodegenerative disease whose primary motor symptoms are tremor, rigidity, bradykinesia and postural instability. Non-motor symptoms, such as depression, decreased quality of life, and an increased dependence on parkinsonian medication, are also observed in PD patients. These symptoms can be alleviated through the administration of approved Parkinsonian medication, but for many individuals with advanced forms of the disease, medication alone is ineffective.

Deep-brain stimulation (DBS) does not cure Parkinson's disease, but it can help manage some of its symptoms and subsequently improve patients’ quality of life. At present, the procedure is used only for patients whose symptoms cannot be adequately controlled with medications, or whose medications have severe side effects. Although deep-brain stimulation’s direct effect on the physiology of brain cells and neurotransmitters is currently debated, it is known that by sending high frequency electrical impulses into specific areas of the brain it can alleviate symptoms and/or directly diminish the side effects induced by Parkinsonian medications, allowing a decrease in medications, or making a medication regimen more tolerable.

In 2002, DBS was approved by the Food and Drug Administration for the treatment of Parkinson's disease patients in the United States. DBS carries the risks of major surgery, with complication rates related to the experience of the surgical teams.

There are several brain structures that can be targeted for deep-brain stimulation in Parkinson’s disease patients. Stimulation to these various sites achieves differing results, so each patient must be assessed individually and a site chosen based on their specific needs. Traditionally, the two most common sites for deep-brain stimulation are the subthalamic nucleus (STN) and the globus pallidus interna (GPi), but other sites, such as the caudal zona incerta and the pallidofugal fibers medial to the STN, are being evaluated and showing promise.

Research is being conducted as of 2007 to predict the onset of tremors before they occur by monitoring activity in the subthalamic nucleus. The goal is to provide stimulating pulses only when they are needed in order to prevent tremors from occurring before they start.

Investigation into Relative Efficacies of DBS in STN and GPi

There is debate over which of the two traditional sites of deep-brain stimulation—the subthalamic nucleus (STN) or the globus pallidus interna (GPi)—is the better target for alleviating Parkinson’s Disease symptoms. Recent research has examined how stimulation in each of these brain structures affects patients with advanced forms of PD in regards to several motor and nonmotor symptoms. Such research is being done in the hope of establishing the optimal site for DBS surgery in patients with advanced PD, for whom these motor and non-motor symptoms have reached a point where they can no longer be effectively treated with Parkinsonian medication.

Associated Effects

Motor ability in Parkinson’s patients is traditionally assessed by the Unified Parkinson’s Disease Rating Scale (UPDRS). Previously, STN stimulation was believed to be more effective than GPi stimulation in treating motor symptoms. The motor scores of patients treated with subthalamic DBS (stimulation to the subthalamic nucleus) were shown to increase on the UPDRS scale, while the scores of those treated with pallidal DBS (stimulation to the globus pallidus interna) remained relatively the same. However, it has recently been demonstrated that the two therapies are not statistically different in their treatment of motor Parkinson’s symptoms. STN and GPi stimulation have been found equally effective in improving force control and dexterity in both hands, among other motor abilities. Improvements in motor function have also been shown to last up to several years after DBS surgery.

Mood changes are often observed in patients who have undergone either STN or GPi deep-brain stimulation. After stimulation to the optimal site of benefit (direct stimulation of the brain area), improvements in overall mood are observed in both subthalamic and pallidal DBS patients. Both STN- and GPi-stimulated patients become happier and less tense after direct DBS, but they also become more angry, irritable, and confused. Indirect stimulation to the ventral or dorsal side of the STN or GPi leads to decreased scores on the visual analogue mood scale (VAMS) for both groups of PD patients, although GPi-stimulated patients tend to fare a bit worse. While changes in mood can certainly arise from STN and GPi stimulation, whether they are positive or negative is highly dependent on the individual patient and the severity of their condition.

Quality of life, which is influenced by both motor and nonmotor Parkinson’s symptoms, is significantly improved by deep-brain stimulation. Subthalamic and pallidal DBS have been found to be equally effective in improving the quality of life in advanced PD patients. However, these improvements decline over time and become insignificant three to four years after surgery. Why quality of life seems to gradually drop to basal levels is still unknown. Also yet to be answered is exactly what factors contribute to overall quality of life and by what degrees.

Subthalamic and pallidal DBS differ in their efficacy of reducing medication use in Parkinson’s patients. The two most common medications prescribed for the treatment of Parkinsonian symptoms are Levodopa and various dopamine agonists. In advanced PD patients, Subthalamic DBS has been shown to more effectively reduce the intake of these drugs than pallidal DBS. More research is needed to support the finding that subthalamic stimulation is more effective in lowering medication intake in post-surgical patients, since this is a major consideration for most individuals undergoing surgery. Currently, research suggests that STN surgery is the better choice for individuals whose major post-surgical goal is medication dose reduction.