Organization of midbrain dopamine systems and the pathophysiology of Parkinson's disease.

Understanding of the pathophysiology of Parkinson disease (PD) has advanced rapidly over the last two decades through basic and clinical studies using modern neuroanatomical, clinical assessment, neuropathological and functional brain imaging methods. Two interacting processes determine the development of functional impairment, neuronal degeneration with selective denervation of specific regions and compensatory responses, which oppose the effects of denervation. The clinical manifestations of PD, at least in early stages, reflect selective degeneration of dopamine neurons in the substantia nigra projecting through the nigrostriatal pathway to the caudal putamen with compensatory changes in this and related systems. Positron emission tomography with specific ligands for the dopamine system is a powerful tool for analysis of both degenerative and compensatory processes in the pathophysiology of Parkinson disease in vivo and can be used to confirm the diagnosis of dopamine deficient Parkinson disease.