Endemic parkinsonism: clusters, biology and clinical features

• Published in: Nature reviews. Neurology 2023-10, Vol.19 (10), p.599-616
• Main Authors: Menšíková, Katerina, Steele, John C., Rosales, Raymond, Colosimo, Carlo, Spencer, Peter, Lannuzel, Annie, Ugawa, Yoshikazu, Sasaki, Ryogen, Giménez-Roldán, Santiago, Matej, Radoslav, Tuckova, Lucie, Hrabos, Dominik, Kolarikova, Kristyna, Vodicka, Radek, Vrtel, Radek, Strnad, Miroslav, Hlustik, Petr, Otruba, Pavel, Prochazka, Martin, Bares, Martin, Boluda, Susana, Buee, Luc, Ransmayr, Gerhard, Kaňovský, Petr
• Format: Article
• Language: English
• Subjects: 631/378/1689; 692/617/375/365; Amyotrophic lateral sclerosis; Biology; Brain diseases; Dementia; Disease; Europe; Guadeloupe - epidemiology; Humans; Hypotheses; Life Sciences; Medicine; Medicine & Public Health; Neurology; Parkinsonian Disorders - epidemiology; Parkinsonian Disorders - genetics; Pathology; Phenotype; Review Article
• ISSN: 1759-4758; 1759-4766
• DOI: 10.1038/s41582-023-00866-3

The term ‘endemic parkinsonism’ refers to diseases that manifest with a dominant parkinsonian syndrome, which can be typical or atypical, and are present only in a particular geographically defined location or population. Ten phenotypes of endemic parkinsonism are currently known: three in the Western Pacific region; two in the Asian-Oceanic region; one in the Caribbean islands of Guadeloupe and Martinique; and four in Europe. Some of these disease entities seem to be disappearing over time and therefore are probably triggered by unique environmental factors. By contrast, other types persist because they are exclusively genetically determined. Given the geographical clustering and potential overlap in biological and clinical features of these exceptionally interesting diseases, this Review provides a historical reference text and offers current perspectives on each of the 10 phenotypes of endemic parkinsonism. Knowledge obtained from the study of these disease entities supports the hypothesis that both genetic and environmental factors contribute to the development of neurodegenerative diseases, not only in endemic parkinsonism but also in general. At the same time, this understanding suggests useful directions for further research in this area. Endemic parkinsonism occurs only in specific locations or populations. Here, Menšíková et al. describe clusters of endemic parkinsonism and highlight that those linked to neurotoxic environmental factors seem to be disappearing, while genetically determined clusters persist. Key points Existing definitions and classification schemes for endemic parkinsonism all have limitations. Foci of endemic parkinsonism are clustered by geographic region as well as clinical features. Endemic parkinsonism has a highly heterogeneous pathological background. Some clusters of endemic parkinsonism are associated with exposure to neurotoxic environmental factors. Other clusters of endemic parkinsonism have a primarily genetic cause. Further study of endemic parkinsonism could illuminate future research into neurodegenerative diseases.