New insights from a multi-ethnic Asian progressive supranuclear palsy cohort

Shen-Yang Lim; Alfand Marl F Dy Closas; Ai Huey Tan; Jia Lun Lim; Yi Jayne Tan; Yuganthini Vijayanathan; Yi Wen Tay; Raihanah Binti Abdul Khalid; Wai Keong Ng; Ruban Kanesalingam; Pablo Martinez-Martin; Azlina Ahmad Annuar; Lei Cheng Lit; Jia Nee Foo; Weng Khong Lim; Adeline Su Lyn Ng; Eng-King Tan

doi:10.1016/j.parkreldis.2023.105296

New insights from a multi-ethnic Asian progressive supranuclear palsy cohort

Parkinsonism Relat Disord. 2023 Mar:108:105296. doi: 10.1016/j.parkreldis.2023.105296. Epub 2023 Jan 20.

Authors

Shen-Yang Lim¹, Alfand Marl F Dy Closas², Ai Huey Tan², Jia Lun Lim³, Yi Jayne Tan⁴, Yuganthini Vijayanathan², Yi Wen Tay³, Raihanah Binti Abdul Khalid⁵, Wai Keong Ng⁶, Ruban Kanesalingam⁷, Pablo Martinez-Martin⁸, Azlina Ahmad Annuar³, Lei Cheng Lit⁹, Jia Nee Foo¹⁰, Weng Khong Lim¹¹, Adeline Su Lyn Ng⁴, Eng-King Tan⁴

Affiliations

¹ Division of Neurology, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; The Mah Pooi Soo & Tan Chin Nam Centre for Parkinson's & Related Disorders, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. Electronic address: limshenyang@gmail.com.
² Division of Neurology, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; The Mah Pooi Soo & Tan Chin Nam Centre for Parkinson's & Related Disorders, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
³ Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
⁴ Department of Neurology, National Neuroscience Institute, Singapore.
⁵ Assunta Hospital, Petaling Jaya, Selangor, Malaysia.
⁶ Subang Jaya Medical Centre, Subang Jaya, Selangor, Malaysia.
⁷ KPJ Puteri Specialist Hospital, Johor Bahru, Malaysia.
⁸ Center for Networked Biomedical Research in Neurodegenerative Diseases (CIBERNED), Carlos III Institute of Health, Madrid, Spain.
⁹ Department of Physiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
¹⁰ Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore.
¹¹ SingHealth Duke-NUS Institute of Precision Medicine, Singapore; Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore.

PMID: 36682278
DOI: 10.1016/j.parkreldis.2023.105296

Abstract

Background: Progressive supranuclear palsy (PSP) is a rare, disabling, neurodegenerative disease, with few studies done in Asian populations.

Methods: We prospectively characterized the clinical features and disease burden in a consecutively-recruited multi-ethnic Asian PSP cohort. Patients were extensively phenotyped using the Movement Disorder Society (MDS-PSP) clinical diagnostic criteria and the PSP-Clinical Deficits Scale (PSP-CDS). Caregiver burden was measured using the modified Zarit Burden Interview (ZBI). Investigations (neuroimaging and genetic tests) were reviewed.

Results: There were 104 patients (64.4% male; 67.3% Chinese, 21.2% Indians, 9.6% Malays), 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 (r_s = 0.45, P < 0.001) and weakly with caregiver burden (r_s = 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.

Conclusions: Significant heterogeneity in clinical features and disease burden, and high rates of RBD symptoms, visual hallucinations, and familial involvement were observed in this relatively large cohort. Our findings highlight important considerations when assessing Asian patients, and provide further support for the notion of overlapping neurobiology between PSP and Lewy body disorders.

Keywords: CADASIL; Caregiver burden; Diagnostic criteria; GBA; Genetics; LRRK2; PSP-CDS; Progressive supranuclear palsy; REM-sleep behaviour disorder; Visual hallucinations; Zarit Burden Interview.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Female
Hallucinations
Humans
Lewy Body Disease*
Male
Neurodegenerative Diseases*
Phenotype
REM Sleep Behavior Disorder*
Supranuclear Palsy, Progressive* / diagnosis