The phenotypic spectrum of progressive supranuclear palsy: a retrospective multicenter study of 100 definite cases.

The phenotypic variability of pro- gressive supranuclear palsy (PSP) may account for its frequent misdiagnosis, in particular in early stages of the disease. However, large multicenter studies to define the frequency and natural history of PSP phe- notypes are missing. In a cohort of 100 autopsy- confirmed patients we studied the phenotypic spec- trum of PSP by retrospective chart review. Patients were derived from five brain banks with expertise in neurodegenerative disorders with referrals from multi- ple academic hospitals. The clinical characteristics of the 100 cases showed remarkable heterogeneity. Most strikingly, only 24% of cases presented as Richardson's Syndrome (RS), and more than half of the cases either showed overlapping features of sev- eral predescribed phenotypes, or features not fitting proposed classification criteria for PSP phenotypes. Classification of patients according to predominant clinical features in the first 2 years of the disease course allowed a more comprehensive description of the phenotypic spectrum. These predominance types differed significantly with regard to survival time and frequency of cognitive deficits. In summary, the pheno- typic spectrum of PSP may be broader and more vari- able than previously described in single-center studies. Thus, too strict clinical criteria defining distinct pheno-