Evaluating the Homogeneity of the PSP-RS Syndrome beyond Core Features

Classic progressive supranuclear palsy RS syndrome (PSP-RS) is characterized by early postural instability/falls and vertical supranuclear gaze palsy, although other signs/symptoms can occur, for example, axial rigidity, bradykinesia, and cognitive dysfunction. The Movement Disorders Society-PSP (MDS-PSP) criteria consider probable PSP-RS a homogenous syndrome, but this has not been tested.

We aim to investigate relationships between signs/symptoms of PSP-RS beyond its core features and determine whether PSP-RS is a homogeneous syndrome.

118 participants who met MDS-PSP criteria for probable PSP-RS were analyzed. All participants received an independent clinical diagnosis based on clinical judgment. We first performed a Network Analysis using qgraph with Spearman's correlation to quantify relationships between 16 signs/symptoms followed by a k-means clustering analysis using the same signs/symptoms to identify possible heterogeneity of the PSP-RS designation.

Five network clusters were identified, reflecting: (1) tremor, (2) sensitivity to bright light, (3) oculomotor function, (4) cognition, and (5) akinetic-rigidity-praxis. Worse akinetic-rigidity was associated with better oculomotor function, but worse cognition. Cluster analysis revealed two clusters. Cluster I (n = 89) had more severe clinical features than Cluster II (n = 29). Cluster II had a higher frequency of participants (37.9%) clinically judged as not PSP-RS: these participants were less likely to have PSP pathology on autopsy (P = 0.03).

Some signs/symptoms of PSP-RS strongly associate and are more likely to co-occur. PSP-RS, as defined by the MDS-PSP criteria includes a subset of participants not clinically judged as PSP-RS who are less likely to have PSP pathology.