To determine whether disease severity at presentation influences mortality in Progressive Supranuclear Palsy (PSP), according to phenotype.

PSP causes Richardson’s syndrome (RS) and variant phenotypes, with selective cognitive, behavioural and motor deficits. Understanding the impact of severity and phenotypic variance will facilitate clinical trial design.

The clinical phenotype at presentation of probable and possible PSP was determined by retrospective application of the MDS 2017 criteria to patients assessed over 20 years at a regional specialist PSP clinic in Cambridge, UK. We assessed the impact of presenting phenotype and severity on survival. Here, we distinguish RS (n=233) from the ‘variant’ PSP syndromes (n=102), and measure severity using PSP-rating-scale (n=255) and MMSE (n=283).

335 people (male=56%, mean age 71.4±7.2 years) were identified with RS (n=233, male=53%, mean age 71.5±7.3 years) or variant PSP (n=102, male=64%, mean age 71.2±6.8 years). Groups had similar levels of disease severity (PSP-rating-scale: 35.6±14 vs 34.6±15.8, p=0.576; MMSE 25.8±3.6 vs 26.2±4.3 p=0.07) and median survival (RS 6.1±2.7 years, variant-PSP 6.8±3.5 years, p=0.2). In RS patients, age and sex-adjusted logistic regression for mortality confirmed the impact of severity using PSP-rating-scale (1-year OR 1.06; 95% CI 1.03-1,10; p<0.001, 3-year OR 1.09; 95% CI 1.06-1.13; p<0.001) and MMSE (1-year OR 0.76; 95% CI 0.67-0.84; p<0.001, 3-year OR 0.77; 95% CI 0.68-0.85; p<0.001). However, in variant PSP, these measures of severity were not predictive of mortality (PSP-rating-scale 1-year OR 1.01; 95% CI 0.95-1.07; p=0.7, 3-year OR 1.04; 95% CI 1.00-1.08; p=0.06 and MMSE 1-year OR 0.90; 95% CI 0.76-1.08; p=0.2, 3-year OR 0.90; 95% CI 0.78-1.02; p=0.1).

The PSP-rating-scale and MMSE scores at presentation predict 1-year and 3-year mortality in patients presenting with PSP-RS but not with variant phenotypes. Other measures of severity of variant PSP syndromes are required to understand variation in prognosis and support clinical trials with survival outcome.