The heterogeneity of idiopathic Parkinson's disease

The diagnosis of Idiopathic Parkinson's disease (IPD) requires post mortem neuropathological confirmation to be secure, since there is marked heterogeneity in the clinical phenotype of these patients. Pathologically confirmed IPD encompasses a spectrum of microscopic appearances with respect to the extent and distribution of Lewy Body deposition, which may reflect the clinical phenotypes observed during life. In this review, we discuss how IPD is currently defined and the purpose and applications of a classification of the disease. We have also performed a systematic review of the literature to present the quantitative evidence on which potential classifications of the disease might be based. This evidence suggests that sub-groups based on age of onset, motor presentation, or subsequent motor phenotype may have some use in predicting disease progression. However, further clinicopathological studies are required to evaluate pathological heterogeneity within these groups. Clinical sub-groups may be related to a variety of as yet unknown risks, including genetic factors for both the familial and sporadic forms of the disease, and may have far reaching consequences for our understanding of disease pathogenesis and treatment strategies.