The DBS controller is about the size of a cell phone, and is used by both the patient and the doctor to program stimulator output. The patient has fewer menu options than the doctor, limited to changing intensity and turning the device off and on.

Photo courtesy of Medtronic, Inc.

Researchers are also investigating the development of a liposome that is essentially a doughnut-like structure loaded with dye, drugs, or nanoparticles. By various methods, this Trojan horse would pass through the BBB, and once inside, releases its payload. One way of getting the liposome past the BBB is known as carrier-mediated transport. The body actively pumps certain vital molecules past the BBB. By chemically linking the liposome to one of these molecules, the liposome is pulled past the barrier in a manner like a train engine pulls a boxcar.

While infusion pumps, cannulas, and Trojan horse delivery methods may offer long-term promise, researchers at the Cleveland Clinic are investigating a simpler therapy: exercise. They are studying how moderate and heavy exercise abates progression of the disease. Study participants are randomly divided into three groups: 1) no exercise; 2) moderate exercise; 3) heavy exercise. Each group completes the Unified Parkinson’s Disease Rate Scale (UPDRS)(a 176 point scale; the higher the number the more severe the disease), a series of instrumented dexterity tests, and a functional MRI. The dexterity test has six degrees of freedom (three axis) and the fMRI measures blood flow in various parts of the brain, for example the globus pallidus and basal ganglia, while subjects perform simple tasks, such as pushing a series of buttons or squeezing a ball. Together these establish a baseline.

The moderate and heavy exercise subjects ride an instrumented bicycle for an hour, three times a week. Then the tests are readministered. While the study is not complete, preliminary results seem to indicate both short-term and long-term improvements in the individuals that exercise. Two unexpected outcomes are the longevity of improvement; up to four weeks after exercise cessation and the improvement in the subjects’ mood. Exercising apparently gives people a sense of controlling their own destiny, a benefit not usually seen by people simply taking medication.

Electronic vs. medicinal

In addition to methods for delivering treatment and the potential for exercise regimes, there are PD therapies that break down into two camps: electronic and medicinal.

For 30 years drug therapy was the only FDA approved method for treating PD. Then, in 1997, Medtronic’s deep brain stimulator (DBS) gained FDA approval. DBS comprises three main components: an implantable pulse generator generally placed in the chest, the lead going into the brain, and the extension wire that connects the lead and pulse generator. Both the doctor and patient have external controllers that adjust the level of stimulation and turn the generator off and on. The electrodes are implanted in the basal ganglia. Pulse shape and frequency are non-invasively adjusted by a clinician who uses a hand held programmer with an LCD screen. Programmable parameters include frequency, amplitude, and pulse width. Communication between the devices is via radio telemetry.

To place the electrodes, an MRI or CT scan of the patients’ brain is used to map the brain. Then a frame or fiducial (a metal screw or marker secured to the skull as a reference point) is positioned and the electrode is inserted through a hole in the skull. The patient, who remains awake, is asked to perform a simple task, such as moving his fingers, which normally causes trembling or involuntary movement. The electrodes are then positioned for maximum effect.

In one study, DBS has been shown to maintain motor-symptom improvements after five years. And after following another group of DBS recipients for several years, researchers concluded that it is better to implement DBS sooner rather than latter. Interestingly, the reason DBS works is not well understood; many researchers are trying to figure out why it does. One theory is that it mimics pallidotomy– surgical destruction of specific cells in the brains globus pallidus. But unlike pallidotomy, DBS is reversible, and benefits are adjustable. Also unlike pallidotomy, DBS can be either bilateral or unilateral depending on the extent of tremor. Pallidotomy can not be done bilaterally without the risk of serious side effects, such as loss of speech.

Two models of stimulators are available, the Activa RC and the Activa PC. The RC is rechargeable and has a nineyear life. A wireless recharger replenishes the batteries. Patients can move about while recharging, which takes about two hours every two weeks. The PC provides continuous stimulation for multiple years. The Activa DBS has been shown to increase periods of good mobility (defined as no symptoms or involuntary excessive movements) from 27% to 74% of a patient’s waking day.

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