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The discovery of MPTP‐induced parkinsonism lends further weight to this theory.59 A rural environment has been associated with an increased risk of developing Parkinson’s disease, suggesting that agents such as herbicides or pesticides may have an aetiological role, although this is limited to approximately 10% of patients with Parkinson’s disease.115 Cigarette smoking has been shown consistently to reduce the risk of developing Parkinson’s disease,3979 although this may be restricted to those with a relatively young age at onset of the disease.127 This effect has been attributed to inhibition of monoamine oxidase type B by products of tobacco combustion.Evidence linking dietary factors to Parkinson’s disease is inconclusive, although one study has shown a lower vitamin E intake in patients with Parkinson’s disease compared with controls.108Overall, most cases of Parkinson’s disease are likely to result from a combination of genetic and environmental factors and these differ between individuals.

The observation of parkinsonian symptoms in heroin addicts who accidentally used 1‐methyl‐4‐phenyl‐1,2,5,6‐tetrahydropyridine (MPTP), a pethidine analogue, has led to the development of a useful animal model for the syndrome.59 An epidemic of encephalitis lethargica in the 1920s was responsible for an outbreak of early onset parkinsonism with associated severe rigidity and respiratory complications.

Although the aetiology of Parkinson’s disease is unknown, it has long been hypothesized that neurodegeneration is induced by genetic, environmental, or infectious disorders.

In Parkinson’s disease, acetylcholine is present in normal amounts in the striatum.

However, dopamine deficiency produces imbalance in the dopamine:acetylcholine ratio, thereby aggravating the symptoms of Parkinson’s disease.

Age is the single most consistent risk factor and it has been estimated that there is a cumulative lifetime risk of one in 40 for developing Parkinson’s disease.100 Loss of pigmented cells in the substantia nigra is the most consistent finding in Parkinson’s disease and normally the quantity of nigral cells diminishes from 425 000 to 200 000 at 80 yr.

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