Investigators have long considered the progressive destruction of nigrostriatal dopaminergic neurons with consequent striatal dopamine deficiency as the pathological hallmark of PD. The presence of Lewy bodies in surviving dopaminergic neurons in the substantia nigra is also considered central to the pathologic confirmation of PD. In recent years it has become evident, however, that neither of these dogmas is absolutely true. While nigrostriatal dopaminergic cellular loss is certainly a central feature of the disease process, the damage is not confined to this pathway and neuronal loss in other locations within the central nervous system has clearly been identified. Moreover, damage in PD is not even confined to the central nervous system. Neuronal loss and even dopamine deficiency are documented within the enteric nervous system of the gastrointestinal tract (Singaram et al. 1995). Peripheral cardiac sympathetic de-nervation is also identified in the setting of PD (Goldstein 2003).
Even the Lewy body is no longer sacrosanct in that the parkin mutation that results in an autosomal recessive form of young-onset PD is not accompanied by the presence of Lewy bodies (Mouradian 2002).
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