Current Management of Parkinsonism

James Parkinson, a London general practitioner and political activist,1 delivered his essay on the shaking palsy in 1817 and encouraged others who "humanely employ anatomical examination" to study the cause and nature of "this malady." Even in his wildest fantasies I seriously doubt that he dreamed of the extent to which his advice would be followed . Today, in spite of a recognized incidence of only 20 cases per 100,000 persons per year; articles concerning this disorder appear in nearly every issue of many neurology journals. The reason for this interest is explained by the significant work that took place in the 1960's. During that period a series of biochemical steps leading from tyrosine to biogenically active amines was elucidated,3 and , further, the action of these amines at brain synapses was convincingly hypothesized.4 Tyrosine is converted to levodopa and then to dopamine, a neurotransmitter. Since dopamine parenterally does not enter the brain , it was found that large doses of its precursor, levodopa, resulted in some levodopa entering the brain, driving the reaction in favor of more dopamine, and therefore enhancing neurotransmission. It is this concept that has excited neurologists out of all proportion to the frequency of Parkinson's disease in the general population. As is now known , the pathology of Parkinson's disease lies in the substantia nigra, 5 where neurons that ordinarily project to the striatum 6 and transmit via dopamine are degenerating; hence the rationale for the use of levodopa as a therapeutic tool. As attractive as this model is, I remain suspicious that the mechanisms are far more complex than as yet determined.