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

Author:

Lim Shen-YangORCID,Dy Closas Alfand Marl F.ORCID,Tan Ai HueyORCID,Lim Jia LunORCID,Tan Yi JayneORCID,Vijayanathan YuganthiniORCID,Tay Yi WenORCID,Abdul Khalid Raihanah binti,Ng Wai Keong,Kanesalingam Ruban,Martinez-Martin PabloORCID,Foo Jia Nee,Lim Weng Khong,Lyn Ng Adeline Su,Tan Eng-King

Abstract

ABSTRACTBackgroundProgressive 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.

Publisher

Cold Spring Harbor Laboratory

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