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PARKINSON'S DISEASE
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TABLE OF CONTENTS
V. SUCCESSES AND ADVERSE EVENTS
Parkinson ’s disease is noted by the degeneration and damage to the dopamine-producing cells in the substantia nigra part of the brain. Dopamine enables the smooth and coordinated movements of the body’s muscles. The primary symptoms of Parkinson’s include tremors, slowness of movement, rigidity, and a difficulty with balance. Parkinson’s can also induce small, cramped handwriting, stiff facial expressions, shuffling when walking, muffled speech, and depression.
There are currently 1.5 million Americans living with Parkinson’s Disease, and 60,000 new cases are diagnosed each year. Eighty-five percent of Parkinson patients are over the age of 65. There are no associated risk factors for primary parkinsonism, instead it affects men and women in almost equal numbers. In addition, the disease shows no social, ethnic, economic, or geographic boundaries. Most forms of Parkinson’s are idiopathic; however, secondary cases can results from toxicity, head trauma, or other medical disorders.
The use of Medtronic’s Activa Therapy was FDA approved in 2002 for the control of Parkinson’s Disease. The device has been used by over 30,000 people in the world market to treat Parkinson’s related symptoms. The Activa Parkinson’s Control Therapy is approved for bilateral stimulation of the internal globus pallidus (GPi) or the subthalamic nucleus (STN). The control therapy is used to reduce some of the symptoms associated with advanced, levodopa-responsive Parkinson’s disease that cannot be adequately controlled with medication. (Medtronic)
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Studies have suggested that Parkinson’s disease may be linked to abnormal and dangerous synchronization of basal ganglia output in the beta frequency band. These oscillations of LFP beta activity is thought to occur through the spiking activity of the dorsal portion of the STN. Based on this theory, DBS helps to modulate the oscillations that occur between the cortex and basal ganglia during movement. It is not believed that DBS acts directly on the dopamine-producing cells of the brain, instead it compensates for the major effects of dopamine loss.
Target sites for DBS in the brain include the globus pallidus (GPi), the subthalamic nucleus (STN), and the VIM of the thalamus. These particular structures consist of clusters of nerve cells that are critical to the control of movement. The stimulation of the VIM is only effective for the treatment of tremors, not the other symptoms of Parkinson’s disease. DBS of the GPi or STN is believed to benefit tremor as well as other parkinsonian disturbances, including rigidity, bradykinesia, and gait problems.
There are many pharmaceutical therapies that help ease the symptoms of Parkinson’s disease. Because many of the symptoms are a direct result of the lack of dopamine, most therapies attempt to replace or mimic dopamine, which helps alleviate many of the adverse movement affects.
Levodopa is the most commonly prescribed drug for Parkinson’s; it can cross the blood-brain barrier and be converted to dopamine in the brain. Segeline, an MAO-B inhibitor, helps prevent the degradation of dopamine, allowing it to have a longer effect. Patients with Parkinson’s can also be prescribed anticholigernic medications, which block nerve impulses that induce muscle movements; however, this therapy is most applicable for patients who are over 70 and mainly experience tremors and drooling.
In severe cases of Parkinson’s disease where patients either don’t respond to drug therapy or face difficult side effects, surgical alternatives can be utilized. Pallidotomy involves making a lesion in the globus pallidus. This results in the destruction of some cells responsible for movement, and has been shown to reduce involuntary movements by 70-90%. Thalamic stimulation, pallidal stimulation, and subthalamic DBS have all been used as surgical therapy formats.
Less invasive therapy approaches include speech therapy, which has been used to treat dysarthrya and dysphagia.
With time patient’s become more and more resistant to the use of drugs, necessitating a change in the medication or an increase in dosage. In addition patients often face many side-effects associated with the drug therapies. Levodopa can cause nausea, vomiting, dry mouth, and dizziness; as the dose is increased patients have experienced dyskinesias. COMT inhibitors are toxic to the liver, can cause diarrhea and dyskinesias, and require that patients have periodic blood tests to determine liver function.
DBS provides patients with fewer disruptive side-effects post implantation than traditional drug therapies. Also there are some Parkinson’s patients who are nonresponsive to current drug therapy who could be offered relief of their symptoms via DBS. The damaging effects of certain drugs such as COMT inhibitors can cause nonreversible damage to the organs; however, DBS procedures offer the advantage of being reversible. There has been significant research into the use of DBS for Parkinson’s and tens of thousands of implants worldwide, suggesting the promising abilities of DBS to drastically improve the lives of those living with Parkinson’s disease.
Over 30,000 patients have used Activa Parkinson’s Control Therapy since its approval on the world market for treatment of the symptoms of Parkinson’s disease. In Medtronic’s worldwide study of Activa there was an observed increase in good motor function and symptom relief by more than 6 hours per day at 12 months postoperatively.
The surgical complications for the treatment of Parkinson’s symptoms are similar to those associated with any stereotactic procedure. These include intracranial bleeding, hardware-related complications such as dislocation of electrodes, lead fracture, and infection. Stimulator side effects include parestesia, tonic muscle contractions, dyskinesia and gait ataxia. Some less common side effects include aggression, mirthful laughter, depression, penile erection, and mania. (Nature 625)
Medtronic (manufacturer of Activa Parkinson’s Control Therapy) clinical studies reported major adverse events such as intracranial hemorrhage, device infection, paresis/asthenia, and hemiplegia/hemiparesis. Ongoing adverse events included the worsening of motor impairment, speech disorders, intermittent continuity, interference from electrical sources, implant breakage, and skin erosion at the site of implant.
Cleveland Clinic - Neurological Institute
University Hospitals Case Medical Center – an affiliate of Case Western Reserve University
UCSF - Parkinson’s Disease Clinic and Research Center