ABSTRACT
BACKGROUND: Development of autonomic failure is associated with more rapid disease course and shorter survival in patients with Parkinson's disease and multiple system atrophy. However, autonomic symptoms have not been specifically assessed as a prognostic factor in progressive supranuclear palsy (PSP). We evaluated whether development of autonomic symptoms is associated with disease progression and survival in PSP. METHODS: A retrospective review of clinical data from consecutive patients with autopsy-confirmed PSP from the Queen Square Brain Bank between January 2012 and November 2016 was performed. Time from disease onset to four autonomic symptoms (constipation, urinary symptoms, erectile dysfunction and orthostatic hypotension) were noted. Time from diagnosis to five disease milestones and survival were calculated to assess disease progression, and their risk was estimated through a Cox proportional hazards model. RESULTS: A total of 103 PSP patients were included. Urinary symptoms and constipation were present in 81% and 71% of cases, respectively. Early development of constipation and urinary symptoms were associated with higher risk of reaching the first disease milestone (respectively, HR: 0.88; 95% CI 0.83 to 0.92; p<0.001; and HR: 0.80; 95% CI 0.75 to 0.86; p<0.001) and with a shorter survival in these patients (respectively, HR: 0.73; 95% CI 0.64 to 0.84; p<0.001; and HR: 0.88; 95% CI 0.80 to 0.96; p=0.004). On multivariate analysis, Richardson syndrome phenotype was the other variable independently associated with shorter survival. CONCLUSIONS: Earlier urinary symptoms and constipation are associated with a more rapid disease progression and reduced survival in patients with PSP.