Objective:

To investigate whether specific signs and symptoms observed in PSP-RS cluster and whether PSP-RS is a homogenous syndrome. 

Background:

The Movement Disorders Society (MDS)-Progressive supranuclear palsy (PSP) criteria recognize PSP-Richardson syndrome (PSP-RS) as a distinct homogenous syndrome. A diagnosis of PSP-RS requires core features of early postural instability, falls and vertical supranuclear gaze palsy/slowing. Many patients with PSP-RS, however, have additional features including dysarthria, executive dysfunction, behavioral changes, and parkinsonian features (tremor, axial +/- appendicular rigidity, bradykinesia).

Design/Methods:

One-hundred eighteen participants meeting MDS-PSP research criteria for probable PSP-RS were recruited by the Neurodegenerative Research Group at Mayo Clinic between 2009 and 2024. We assessed relationships between 16 neurological signs/symptoms, as well as clinical diagnoses made independent of the MDS-PSP criteria. We first performed a Network Analysis and Spearman correlations to identify relationships between the signs and symptoms followed by a k-means cluster analysis.  

Results:

Fifty-three/118 patients were female. Mean age at onset 66 years (range:48-80). The 16 features sorted into five distinct network groups. Sensitivity to bright light and tremor sorted into 2 distinct groups and showed no inter-cluster relationships to other features. Worse neck rigidity and bradykinesia were associated with better ocular motor function, while worse bradykinesia was associated with worse cognitive impairment. Cluster analysis revealed two distinct clusters. Cluster I (n=89) was characterized by patients with more severe dysarthria, parkinsonian features, cognitive and executive dysfunction, and ocular motor impairment (all p<0.05). Cluster II (n=29) consisted of a higher frequency of participants not clinically diagnosed with PSP-RS (33.3% vs 14.8%; p=0.01). There was no difference in demographic features including gender, race, education, age at onset, or disease duration between clusters.  

Conclusions:

Some neurological signs/symptoms occurring in PSP-RS are associated and tend to occur together. Probable PSP-RS, as defined by the MDS-PSP criteria, is not a homogeneous syndrome.