Treatment of Parkinson's disease.

Pharmacotherapy with levodopa for Parkinson''s disease provides symptomatic benefit, but fluctuations in (or loss of) response may eventually occur. Dopamine agonists are also helpful and, when taken with low doses of levodopa, often provide sustained benefit with fewer side effects; novel agonists and new methods for their administration are therefore under study. Other therapeutic strategies are being explored, including the use of type B monoamine oxidase inhibitors to reduce the metabolic breakdown of dopamine, catechol-O-methyltransferase inhibitors to retard the breakdown of levodopa, norepinephrine precursors to compensate for deficiency of this neurotransmitter, glutamate antagonists to counteract the effects of the subthalamic nucleus, and various neurotrophic factors to influence dopaminergic nigrostriatal cells. Surgical procedures involving pallidotomy are sometimes helpful. Those involving cerebral transplantation of adrenal medullary or fetal mesencephalic tissue have yielded mixed results; benefits may relate to the presence of growth factors in the transplanted tissue. The transplantation of genetically engineered cell lines will probably become the optimal transplantation procedure. The cause of Parkinson''s disease may relate to oxidant stress and the generation of free radicals. It is not clear whether treatment with selegiline hydrochloride (a type B monoamine oxidase inhibitor) delays the progression of Parkinson''s disease, because the drug also exerts a mild symptomatic effect. Daily treatment with vitamin E (a scavenger of free radicals) does not influence disease progression, perhaps because of limited penetration into the brain.     

Drug treatment of Parkinson's disease.

A wide variety of drugs is available for treating Parkinson''s disease, including anticholinergics, amantadine levodopa, dopamine agonists, and selegiline. In younger patients (less than 50) levodopa is usually delayed provided that adequate relief of symptoms can be achieved with other drugs. In older patients (greater than 70) levodopa should be started as soon as symptom relief is required. Between these ages there is no consensus, but at present most such patients should probably be given controlled release levodopa before a dopamine agonist is added. Fluctuations can often be alleviated by giving controlled release preparations of levodopa, by giving small doses at frequent intervals, by adding selegiline or a long acting oral agonist, or by subcutaneous apomorphine. Dyskinesia can be peak dose, diphasic, or "off period." The diphasic form is hardest to alleviate. Psychiatric side effects should initially be managed by changing the antiparkinsonian treatment before resorting to antipsychotic drugs.     

A community survey of Parkinson's disease.

In a rural community of 80,000 people 69 patients were identified as having a diagnosis of Parkinson''s disease. After interview and examination we found that 55 met the generally accepted diagnostic criteria for Parkinson''s disease, 4 had possible Parkinson''s disease, 6 had essential tremor, 2 had dementia and 2 had other conditions. The patients with Parkinson''s disease had clinical and epidemiologic characteristics similar to those of patients in previous, mainly hospital-based, studies. These characteristics included mean age at onset (63 years), frequency rate of dementia (20%) and presence of postural tremor (11%). The pattern of treatment varied, some patients receiving more medication than is usual for the severity of their illness, and some patients receiving less than is usual. Parkinson''s disease can be difficult to diagnose and manage because of the clinical variation between patients in presentation and response to treatment.