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Most people with Parkinson's disease are described as having idiopathic Parkinson's disease (having no specific known cause). There are far less common causes of Parkinson's disease including genetic, toxins, head trauma, cerebral anoxia, and drug-induced Parkinson's disease. . Genetic. In recent years, a number of specific genetic mutations causing Parkinson's disease have been discovered, including in certain populations (Contursi, Italy). These account for a small minority of cases of Parkinson's disease. Someone who has Parkinson's disease is more likely to have relatives that also have Parkinson's disease. However, this does not mean that the disorder has been passed on genetically. .
Toxins . One theory holds that the disease may result in many or even most cases from the combination of a genetically determined vulnerability to environmental toxins along with exposure to those toxins. This hypothesis is consistent with the fact that Parkinson's disease is not distributed homogeneously throughout the population; its incidence varies geographically. However, the fact that the first appearance of the syndrome predates the first synthesis of the compounds often attributed to causing Parkinson's disease indicates that these recently synthesized compounds cannot be the sole cause of Parkinsonism. The toxins most strongly suspected at present are certain pesticides and transition-series metals such as manganese or iron, especially those that generate reactive oxygen species, and/or bind to neuromelanin, as originally suggested by G.C. Cotzias. In the Cancer Prevention Study II Nutrition Cohort, a longitudinal investigation, individuals who were exposed to pesticides had a 70% higher incidence of PD than individuals who were not exposed. . The tragedy of a group of drug addicts in California in the early 1980s who consumed a contaminated and illicitly produced batch of the synthetic opiate MPPP brought to light MPTP (pro-toxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyidine) as a specific cause of Parkinson symptoms. This made it possible to develop the first animal model for Parkinson's. MPTP's toxicity likely comes from the generation of reactive oxygen species through tyrosine hydroxylation. The Case of the Frozen Addicts by J. William Langston (Vintage, New York, June 25, 1996) documents this tragedy and describes the first attempts at fetal brain tissue transplants to treat PD. . Other toxin-based models employ PCBs, paraquat (a herbicide) in combination with maneb (a fungicide), rotenone (an insecticide), and specific organochlorine pesticides including dieldrin and lindane. Rotenone is an inhibitor of complex 1 of the electron transport chain. It easily crosses membranes due to its extremely hydrophobic properties. Rotenone, therefore, does not rely on the dopamine transporter to enter into the cytoplasm. Numerous studies have found an increase in PD in persons who consume rural well water; researchers theorize that water consumption is a proxy measure of pesticide exposure. In agreement with this hypothesis are studies which have found a dose-dependent increase in PD in persons exposed to agricultural chemicals. . Head trauma Past episodes of head trauma are reported more frequently by individuals with Parkinson's disease than by others in the population. A recent methodologically strong retrospective study found that those who have experienced a head injury are four times more likely to develop Parkinson’s disease than those who have never suffered a head injury. The risk of developing Parkinson’s increases eightfold for patients who have had head trauma requiring hospitalization, and it increases 11-fold for patients who had experienced severe head injury. The authors comment that since head trauma is a rare event, the contribution to PD incidence is slight. They express further concern that their results may be biased by recall, i.e., the PD patients because they reflect upon the causes of their illness, may remember head trauma better than the non-ill control subjects. These limitations were overcome recently by Tanner and colleagues, who found a similar risk of 3.8, with increasing risk associated with more severe injury and hospitalization. However, whether the head trauma actually contributed to Parkinson's disease development or the early symptoms of clumsiness associated with Parkinson's causes individuals to have more head trauma is still unknown.
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Causes of PD
