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

Abstract

The phenotypic variability of progressive 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 phenotypes are missing. In a cohort of 100 autopsy-confirmed patients we studied the phenotypic spectrum of PSP by retrospective chart review. Patients were derived from five brain banks with expertise in neurodegenerative disorders with referrals from multiple 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 several 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 phenotypic spectrum of PSP may be broader and more variable than previously described in single-center studies. Thus, too strict clinical criteria defining distinct phenotypes may not reflect this variability. A more pragmatic clinical approach using predominance types could potentially be more helpful in the early recognition of and for making prognostic predictions for these patients. Given the limitations arising from the retrospective nature of this analysis, a systematic validation in a prospective cohort study is imperative.

The frontal assessment battery is not useful to discriminate progressive supranuclear palsy from frontotemporal dementias

“…Thus, we suggest that this should be taken into account by clinicians administering this test. Of note, our patients had Richardson's syndrome and it is unknown whether the FAB could differentiate other PSP phenotypes such as PSP-Parkinsonism from PD and MSA-P [10]. Moreover, our cohort had already established clinical diagnoses and it remains unknown whether the FAB is useful in discriminating PSP with PD or MSA-P, in the early stages of these disorders.…”

The phenotypic spectrum of progressive supranuclear palsy

“…More recently, definitions of PSP subgroups, termed PSP-phenotypes, have been proposed [3]. There is ongoing debate whether these phenotypes represent separate entities, since clinical syndromes may overlap and may progress into PSP-RS at later disease stages [8,9]. However, different modes of initial presentation seem to predict different patterns of disease progression and survival time [3,8,9].…”

Increased basal ganglia binding of 18F‐AV‐1451 in patients with progressive supranuclear palsy

“…The neuropathology is characterized by tau‐positive inclusions containing primarily the 4‐repeat (4R) isoform of tau and regional brain atrophy affecting the basal ganglia, the frontal lobe, and the dentate nucleus 3, 4. During the early stages of disease progression, it is often difficult to distinguish PSP from Parkinson's disease, multiple system atrophy, or corticobasal degeneration, and consequently a significant proportion of patients with PSP does not receive a correct diagnosis 5. Cerebrospinal fluid levels of neurofilament might distinguish atypical parkinsonism from Parkinson's disease but do not discriminate between PSP, multiple system atrophy, or corticobasal degeneration 6.…”