Background

Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease with diverse clinical phenotypes, prompting the development of new diagnostic criteria known as the MDS-PSP classification. However, little is known about the prognostic value of this classification in order to better stratify patients for the clinical trials.

Objective

To assess the impact of the different clinical phenotypes according to the MDS-PSP classification on prognosis using the clinical milestones of death, severe dysphagia, institutionalization, and need for walking aid.

Methods

A prospective cohort of 205 PSP patients from Lille University Hospital was analyzed retrospectively. Patients were classified into different MSD-PSP phenotypes according to their clinical presentation after 3 years of follow-up. The milestones of death, severe dysphagia, institutionalization, and need for walking aid were recorded, and a survival analysis was performed to describe the prognosis of each disease presentation.

Results

Median survival time was 6.4 (interquartile range (IQR): 4.8–8.6) years and mean diagnostic delay from symptom onset was 38.1 ± 22.5 months. PSP Richardson Syndrome (PSP-RS) had a poorer survival rate and a higher occurrence of severe dysphagia and need for walking aid compared to PSP variants such as PSP Parkinsonism (PSP-P), PSP postural instability without ocular motor dysfunction (PSP-PI), and other rare phenotypes.

Conclusions

PSP-RS has a less favorable prognosis compared to PSP variants stratified according to the MDS-PSP classification. This classification could assist in selecting patients for clinical trials and help design outcomes that account for the disease heterogeneity.

Plain language summary

Progressive supranuclear palsy (PSP) is a rare and debilitating neurodegenerative disease marked by diverse combination of motor and cognitive symptoms. No treatment is currently available to slow down disease progression. The multiple clinical presentations of PSP compromise clinical trials. Thus, we aimed to study the differential prognosis of the different forms of the disease. We showed that PSP-Richardson Syndrome (PSP-RS), which is the most frequent presentation, seems to have a poorer prognosis than other variants on survival and other disability criteria such as severe dysphagia occurrence. This study suggests that these differences should account to improve the design of future clinical trials.

Search results

Clinical prognostic factors in progressive supranuclear palsy: Implications for clinical trials