Background
Parkinson's disease, which results from the death of nerve cells in the brain, is a chronic, degenerative neurological disorder that affects at least one million people in the United States and more than five million worldwide. It affects adults of all races, and the risk of developing the disease increases with age. Recent research indicates that one in 100 people over the age of 60suffer from this debilitating and progressive disease (symptoms continue to worsen over time).
Motor impairments (also called cardinal symptoms because they are the hallmark of the disease) include resting tremor, slowness of movement (bradykinesia), rigidity, and postural instability. Non-motor symptoms include sleep difficulties, loss of sense of smell, constipation, speech and swallowing problems, and low blood pressure when standing. There could be also mood disorders and cognitive impairment ranging from mild memory difficulties to dementia.
The area of the brain that is most affected by Parkinson’s disease is the substantia nigra in the brainstem. Nerve cells lost there are the ones that produce dopamine, a chemical involved in communication to the part of the brain that controls movement and coordination. As the disease progresses, the amount of dopamine produced in the brain decreases, leaving the patient unable to control movement normally.
Treatment
Currently there is no cure for Parkinson’s disease--the therapies listed here (drugs or surgery) provide only symptomatic improvement.
Drug Therapy:
Drug therapy involves stimulating communication to the motor part of the brain. Different classes of drugs can provide more dopamine to the brain (levodopa therapy), reduce dopamine breakdown (MAO-inhibitors or COMT-inhibitors), or mimic the effects of dopamine (dopamine agonists). In the course of the disease, as it progresses, there is a need to move to a more potent class of medication like levodopa therapy. However, within a few years of initiating levodopa therapy, patients develop refractory Parkinson's disease symptoms, motor fluctuations (on off periods), and dyskinesia. Even with optimal intervals and dosages of medication, the amount of time spent with good motor control declines in late-stage Parkinson's disease, and it is at this point that patients consider surgical options to improve their quality of life.
Surgery:
Surgical options to improve motor symptoms include implantation of deep brain stimulation (DBS) device or surgical lesioning of a specific area in the brain.
Deep Brain Stimulation Device:
Implantation of a DBS device or “Pacemaker” takes two steps. First, the surgeon creates an opening in the patient’s skull and implants electrodes into a specific area in the brain (the globus pallidus or subthalamic nucleus). Then the surgeon implants the stimulator under the skin of the patient’s collar bone and tunnels the electrodes under the skin of the neck to connect them to those implanted in the brain. Small electrical pulses emitted from the DBS device block some of the Parkinson's symptoms and reduce the adverse effects associated with prolonged use of drugs. DBS is the most common surgical intervention used to treat Parkinson’s disease.
Lesioning:
Lesioning is a procedure whereby a small volume of tissue is being destroyed. In a lesioning procedure done for treatment of Parkinson’s disease the targeted volume cells inhibit motor function, and destroying these cells can improves the patient’s residual motor capacity, (pallidotomy or thalatomy). This procedure can be done by radiosurgery or Radiofrequency ablation.
Radiosurgery:
Using stereotactic radio surgery the radiation oncologist deliver a very high dose of ionizing radiation to a predefine small volume in the brain thereby destroying all living cells in this volume.
Radiofrequency ablation:
In a radiofrequency ablation procedure the surgeon heats a small volume in the brain via a needle inserted into it through a small opening (bore hole) in the skull. This temperature rise cooks and kills the living cells by heat denaturation of the cell proteins, just like cooking an egg.
Focused Ultrasound
Focused ultrasound is a completely noninvasive way to perform the lesioning procedure described above. Using this treatment modality in conjunction with image guidance, the physician directs a focused beam of acoustic energy through the patient’s scalp, skull, and brain to thermally coagulate of small area of the brain, thereby destroying targeted tissue without damaging nearby tissue or the tissues through which the beam passes on its way to the target.
Using magnetic resonance imaging (MRI) thermometry to monitor and control the focused ultrasound energy delivery, the treating physician is able to identify the region of energy deposition at the ultrasound focus point before generating ablative temperatures. This use of thermometry allows closed loop control on the location and extent of the thermal tissue necrosis.
Potential benefits of Focused Ultrasound Treatment for Parkinson Disease
(As this procedure is either theoretical at the moment or in a very early stages the benefits listed here were not yet proven in any clinical trial).
- Focused Ultrasound treatment is non-invasive just like radio-surgery, however it therapeutic effects are immediate and it does not use ionizing-radiation and thereby does not have the adverse effect and limitation associated with it.
- Compared to radio-frequency ablation, focused ultrasound is non-invasive and therefore has significant reduced risk for infection. Also as focused ultrasound is done under closed loop thermal feedback, it is more likely to damage only targeted tissue and spare non-targeted healthy brain.
- Compared to implantation of deep brain stimulation device, focused ultrasound is a onetime procedure, and does not require subsequent procedure to replace batteries. Focused Ultrasound also does not involve implantation of a foreign body, and thereby carries a reduced risk of blood clots creation.
- Since there is no need to insert electrodes or needles the collateral damage to the brain is reduced
Current State of Focused Ultrasound in Parkinson's Disease
Research on the use of focused ultrasound to treat Parkinson’s disease has begun. The application of focused ultrasound includes different treatment possibilities, including noninvasive thermal lesioning of a small area in the brain (as described above) and improving the delivery of drugs (dopamine), gene therapy, or even delivering stem cells to the brain by using focused ultrasound to create a reversible opening of blood-brain barrier.
At this time there are only anecdotal cases of patients receiving focused ultrasound lesioning therapy for Parkinson’s disease, and we currently have no clinical experience in using it in any other way for this specific indication.
A pilot study to evaluate the safety and efficacy of the focused ultrasound lesioning procedure for treating of Parkinson's disease should begin in the United States in the second quarter of 2012.
The Focused Ultrasound Surgery Foundation is collaborating and funding a functional neurosurgical program with leading medical centers. At this stage of the program, researchers have treated 15 essential tremor (ET) patients at the University of Virginia and plan to treat an additional 15 ET patients during the second half of 2012.
Preclinical studies at Arizona State University, UCLA, and the Brigham and Women’s Hospital in Boston suggest that the mechanical effects of ultrasound alone may be sufficient to both excite and suppress neuronal circuits. Primate and small animal studies from multiple research laboratories have shown it is possible to create a reversible opening of the blood-brain barrier, which allows transport of drugs, antibodies, and even cells.
Clinical Trials
Clinical trials using focused ultrasound therapy are scheduled to begin toward the second quarter of 2012 at sites in North America and Europe.
University of Virginia trial would include 30 patients with tremor dominant Parkinson, and once completer a follow-up study to evaluate the ability to treat Parkinson bradykinesia is planned.
Patient Advocacy and Online Resources
The Michael J. Fox Foundation is dedicated to finding a cure for Parkinson’s disease through an aggressively funded research agenda and to ensuring the development of improved therapies for those living with Parkinson’s today. http://www.michaeljfox.org
The Parkinson’s Disease Foundation (PDF) is a leading national presence in Parkinson’s disease research, education, and public advocacy. They also have a national help line and answer questions via Email. http://www.pdf.org
The Wikipedia entry on Parkinson’s disease is extensive and covers everything from symptoms and pathology to treatment options, research ideas, and notable cases. http://en.wikipedia.org/wiki/Parkinson's_diseaseVendors
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Notable Papers
As this procedure is only at the early investigational stages, there is still no clinical data published.
For pre-clinical publication and article on Parkinson disease in general please click on the link below.