ASK DR. BAUGHAN                                                              February 24, 2001

THE PARKINSON’S PUZZLE

Parkinson’s Disease is a puzzling neurologic disease that typically affects older men, but may affect younger persons and older women as well.  Although we know many parts of the nervous system that malfunction with Parkinson’s disease and many of the neurochemical abnormalities in Parkinson’s disease, there is no blood test, CT scan or MRI which shows the abnormalities or conclusively proves Parkinson’s Disease.  The diagnosis relies on observation of specific signs and symptoms.

The cardinal features of Parkinson’s Disease include a resting tremor (meaning it lessens with voluntary motion), bradykinesia (slowed movements), rigidity (often including a loss of facial expressiveness), and asymmetry (one side affected more than another).  The bradykinesia and rigidity also involve the many small reflexes we ordinarily have in maintaining balance when we walk.  Therefore, people with Parkinson’s may fall frequently.  More advanced cases may lead to dementia and/or difficulty speaking and swallowing.

There is evidence to support the hypotheses that Parkinson’s Disease is a genetic disorder, or it may be caused by internal toxins the body makes with aging, and some environmental toxins, although no specific chemicals have been implicated.  The traditional key area of the brain affected is a small area in the brain stem called the substantia nigra (“black substance” for non-Latin speakers).  This area, only several millimeters in size, is rich in nerves that produce dopamine, one of the key chemicals involved in transmitting nerve signals from one nerve to another.  In Parkinson’s  Disease, this area degenerates, resulting in a deficiency of dopamine.  We are learning that multiple other areas of the brain are involved in Parkinson’s Disease, some that have to do with dopamine, some which do not.  But replacing dopamine in the brain has been the mainstay of treatment for decades.  There is no cure, but symptoms can be lessened in many patients.

Why can’t we just give the patient dopamine?  Giving dopamine by mouth or IV can raise blood pressure dramatically (which is why we give it to very ill patients with dangerously low blood pressure in intensive care units).  It can stimulate nerves and muscles in our arms and legs, causing spasms and cramps, but it does not get to the brain due to a unique aspect of the blood vessels in the brain that restricts the absorption of many chemicals into the brain tissue.  This is called the blood-brain barrier.  Dopamine as a pill also gets metabolized very quickly before it even has a chance to get to the brain.

The breakthrough treatment for Parkinson’s Disease several decades ago was Sinemet, which is a combination of L-dopa and carbidopa.  The carbidopa is a decoy for the enzymes that breakdown dopamine and similar substances.  By tying up those enzymes, more L-dopa can make it to the brain.  L-dopa can cross the blood-brain barrier, then it gets metabolized to dopamine.  It helps most consistently with the bradykinesia.  Unfortunately, it can cause nausea, hallucinations, psychosis, confusion, sedation, and sleep disturbance.  In time, it can cause involuntary movements or a worsening rigidity or immobility.

In more recent years, there have been multiple medications that work by helping lower doses of L-dopa get to the key parts of the brain without overstimulating the rest of the nervous system.  Others stimulate certain dopamine receptors in the brain without having the shot-gun stimulation of all dopamine receptors that L-dopa does.  These medications have been most helpful in early stages of Parkinson’s Disease in delaying the need for Sinemet or lowering the effective dose, thus minimizing side effects.

With all this difficulty trying to get medicine to a tiny part of the brain when the medicine affects nerves all over the body, there was understandable enthusiasm when reports arose of surgical techniques to implant brain tissue to replace the degenerated substantia nigra.  Unfortunately, the results have been very inconsistent, from some benefit to none to worsening.  Other surgical techniques are showing promise for certain features of Parkinson’s, but we still have a long way to go to solve the puzzle.