Parkinson’s Disease:

Parkinson's disease is a devastating condition. It is a topic so rich that one could dedicate a lifetime's work to it. However, the main points to make are as follows.

Symptoms

The most noticeable symptoms of Parkinson's disease are resting tremors, that is, tremors that do not manifest themselves during movement or sleep, and movements tend to be jerky. There are also involuntary movements, and any voluntary movement tends to be difficult to initiate and slow in action. As the disease progresses, stance can become stooped and speech problems can develop. There is also often excess sweating, and micrographia (unusually tiny handwriting).

Neuropathological Observations:

Neuropathological observations have found that Parkinson’s suffers have a great deal of degradation in the substantia nigra, where there appears to be a high number of Lewy bodies found. But Lewy bodies are not just confined to the substantia nigra, and nor are they exclusive to Parkinson’s sufferers. A very significant observation has been made, initially by Ehringer and Horneykiewicz in 1960, that there is a up to a greater than 50% depletion of dopamine in the striatum (caudate nucleus and putamen), and the substantia nigra in Parkinson’s disease patients. The striatum is involved in planning movement, so problems with this area could manifest as part of the motor problems that suffers have. The brain can cope with some drop in dopamine here. It has been shown that it can compensate up to a critical level of about an 80% drop in dopamine, but after this parkinsonian symptoms occur.

Treatments:

Since a deficit of dopamine seems to be a problem, the natural conclusion researchers came up with was that an appropriate treatment for Parkinson’s disease should involve the replacement, or replenishment, of that lost dopamine. Initial trials involving the simple administration of dopamine into the bloodstream proved unsuccessful due to the dopamine being unable to get through the blood-brain barrier. However, it was found that the precursor to dopamine, L-DOPA, could find its way into the brain, and from there, could boost the manufacture of dopamine in the brain. However, there are side effects such as dyskinesias (inability to control movements), and psychotic disturbances (related to those suffered in schizophrenia). Another method of treatment takes a slightly different approach and administers dopamine agonists to try and stimulate the production of dopamine in effected areas. This tends to have fewer side effects than the L-DOPA method, and works quite effectively when the dosage of dopamine agonist is given with a very small dosage of L-DOPA in addition. However, none of these methods are any use in the long term. Their efficacy is reduced over time due to the progressive deterioration of the cells the extra dopamine is intended to aid.

There is a procedure intended to halt and maybe reverse the degeneration suffered by Parkinson's patients, but it is limited in its success. By implanting dopamine producing tissue into the substantia nigra it is hoped that this new tissue will act to replace that which is lost. This procedure is only really effective if the implanted tissue is foetal substantia nigra tissue as this is capable of forming neural connections. Although the treatment can work, the limit is one of time, as after about a year, the implanted tissue either dies off or degrades itself. The drug treatments have been shown to be more effective anyway.

Causes of Parkinson's Disease:

Much research has been conducted into the aetiology of Parkinson's disease. It is significant that the degeneration is limited to just a fairly select group of cells. There may be some inherited factor at play, but there is contrasting evidence. Johnson et al. (1990) conducted studies with monozygotic and dizygotic twins and concluded that there was no evidence to suggest an inherited trait, but other studies suggest the opposite. Some believe that there may not be a genetic deficiency that leads directly to the onset of Parkinson's as such, but instead inherited genetic traits that may contribute to other factors developing, the combination of which go on to cause the disorder. There has been suggestion that there may be a viral cause. This is based on the 1915-1926 outbreak of encephalitis lethargica in Europe. The 60% of sufferers who survived the illness developed parkinsonian symptoms, though this was not Parkinson's disease itself. The illness did cause a degeneration of tissue in the substantia nigra, so it is easy to see why it may be possible that Parkinson's might have a viral cause.

Some of the most compelling evidence has come from the substance MPTP which was mistakenly sold to heroin addicts in the 1980s as a narcotic substitute. This substance produced very parkinsonian symptoms and does in fact cause degeneration of the substantia nigra while leaving other areas unaffected. More work is needed before definite conclusions can be made.

Conclusions:

Since the causes of Parkinson's disease have not yet been properly identified, then the pursuit of an effective treatment is somewhat of a non-starter. Until such information is available, suffers are doomed to develop the disease further and further, and those who are just getting symptoms have no chance of prevention of the illness.

Bibliography:

"Brain, Biochemestry and Brain Disorders", P. G. Strange, Oxford University Press, 1992