"Parkinsonism" is a relatively common complex of neurologic symptoms that can be seen with many types of extrapyramidal disease. This constellation of symptoms appears as the end product of many degenerative disorders of the brain, although some produce the symptoms much earlier in the course than others. For example, most patients with a generalized dementing condition of the brain will eventually develop symptoms of parkinsonism. However, this occurs quite late in the course of the disease for most of these conditions. Cerebrovascular disease can also target the extrapyramidal system (especially when diffuse), leading to parkinsonian symptoms. On the other hand, symptoms occur relatively early in conditions that selectively target the basal ganglia and related structures. Examples include progressive supranuclear palsy, cortico-basal ganglionic degeneration, striatonigral degeneration, multi-system atrophy and diffuse Lewy body disease.
In the case of idiopathic Parkinson's disease, the constellation has been related specifically to deficient function of the nigrostriatal dopaminergic systems. In this case, the major underlying pathologic abnormality is either a degeneration of neurons of the substantia nigra pars compacta (which are the source of the dopamine in the striate nuclei), or a drug-induced suppression of dopamine effectiveness. The latter is a common cause of the parkinsonian syndrome because of the widespread use of certain neuroleptic (tranquilizing) drugs (phenothiazines, butyrophenones, and reserpine) and it can be easily reversed by discontinuation of the drug.
A rare cause of acute and irreversible parkinsonism is poisoning with the "designer drug" MPTP, a derivative of the narcotic analgesic meperidine. The free radical breakdown product of MPTP, MPP+ appears to be the toxic molecule, which destroys the pigmented dopaminergic cells in the substantia nigra. A major experimental model has arisen from this tragic discovery (monkeys and other mammals also develop the parkinsonian syndrome when exposed to this toxin). The toxicity can be blocked by antioxidant therapy (Vitamin E, etc.) and a monoamine inhibitor, deprenyl. This has led to speculation concerning the etiology of parkinsonism and to clinical trials of both entities to determine a possible prophylactic effect in idiopathic parkinsonism.
Ameliorative but not curative medical therapy is now available for Parkinson's patients, mainly in the form of dopamine repletion or deep brain stimulation.