Current concepts in clinical therapeutics: Parkinson's disease

The etiology, pathophysiology, diagnosis and clinical presentation, and clinical management of Parkinson's disease are reviewed. The cause of Parkinson's disease, a progressive, degenerative neurologic motor disorder, is unknown. Both endogenous and environmental factors appear to play a role. The clinical features of parkinsonism result from a depletion in dopaminergic transmission in the corpus striatum; the dopamine deficiency is caused by a loss of melanin-containing nerve cells within the substantia nigra and locus ceruleus. In the remaining neurons, hyalin-like masses called Lewy bodies increase in number, but the importance of this is unclear. The diagnosis of Parkinson's disease is based on the clinical presentation of the patient, which initially includes sensory complaints of aching pains, paresthesias, numbness, and coldness. As the disease progresses, the four classic symptoms become prominent: tremor, rigidity, bradykinesia, and postural difficulties. Drug therapy is the cornerstone of clinical management of Parkinson's disease, but no treatment has been found that will retard or reverse the disease. Therapy is usually initiated with anticholinergic agents such as biperiden hydrochloride or trihexyphenidyl hydrochloride with or without amantadine. The mainstay of therapy is levodopa, which is used in combination with dopa decarboxylase inhibitors to decrease the peripheral conversion of levodopa to dopamine. Bromocriptine is a dopamine agonist useful in treating Parkinson's disease. Therapy, which must continue for life, eventually becomes less effective or completely ineffective in all patients. Drug therapy has improved greatly the functional ability of patients with Parkinson's disease, but new agents that can extend the length of effective treatment or reverse the disease are needed.