Prospective Characterization of Progressive Supranuclear Palsy in a Multi-Ethnic Asian Cohort

BackgroundProgressive supranuclear palsy (PSP) is a rare, disabling, neurodegenerative disease. There are limited studies on the spectrum of PSP predominance-types and their clinico-demographic features among Asian patients. We prospectively characterized the clinical features, disease severity, and caregiver burden in a multi-ethnic Asian PSP cohort. MethodsConsecutively-recruited patients with PSP (n=104, 64.4% male; 67.3% Chinese, 21.2% Indians, 9.6% Malays) were extensively phenotyped by a movement disorders neurologist using the MDS-PSP clinical diagnostic criteria and PSP-Clinical Deficits Scale (PSP-CDS). Caregiver burden was measured using the modified Zarit Burden Interview (ZBI). Investigations were reviewed to help rule out potential PSP mimics. ResultsThere were 104 patients, consisting of 48.1% Richardson syndrome (PSP-RS), 37.5% parkinsonian phenotype (PSP-P), and 10.6% progressive gait freezing phenotype (PSP-PGF). Mean age at motor onset was 66.3{+/-}7.7 years, with no significant differences between the PSP phenotypes. Interestingly, REM-sleep behaviour disorder (RBD) symptoms and visual hallucinations (considered rare in PSP) were reported in 23.5% and 22.8% of patients, respectively, and a family history of possible neurodegenerative or movement disorder in 20.4%. PSP-CDS scores were highest (worst) in PSP-RS; and correlated moderately with disease duration (rs=0.45, P<0.001) and weakly with caregiver burden (rs=0.22, P=0.029) in the overall cohort. Three of 48 (6.3%) patients who had whole-exome sequencing harboured pathogenic/likely pathogenic GBA variants. ConclusionsThis prospective characterization of a relatively large cohort of Asian PSP patients depicts significant heterogeneity in clinical features and disease burden. Unexpectedly high rates of RBD symptoms, visual hallucinations, and familial involvement warrant further study.