Abstract
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overlap in biological and clinical features of these exceptionally interesting diseases, this Review provides a historical reference text and offers current perspectives on each of the 10 phenotypes of endemic parkinsonism.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.
Key points
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Existing definitions and classification schemes for endemic parkinsonism all have limitations.
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Foci of endemic parkinsonism are clustered by geographic region as well as clinical features.
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Endemic parkinsonism has a highly heterogeneous pathological background.
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Some clusters of endemic parkinsonism are associated with exposure to neurotoxic environmental factors.
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Other clusters of endemic parkinsonism have a primarily genetic cause.
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Further study of endemic parkinsonism could illuminate future research into neurodegenerative diseases.
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References
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Acknowledgements
The research work of authors is supported by the European Regional Development Fund — Project ENOCH (No. Z.02.1.01/0.0/0.0/16_019/0000868 to L.T., D.H., K.K. and M.S.); a grant from the Ministry of Health of the Czech Republic for the conceptual development of a research organization (FNOL 0098892) RVO FNOL 2022 to K.M., L.T. and D.H.; and Ministry of Health of the Czech Republic grant NV19-14-00090 to K.M., L.T., D.H. and R.M. The authors thank A. Johnson and S.E. Cook for language editing and thank A. Vydrova and Z. Malinska for providing the Supplementary figures. The authors thank the Third World Medical Research Foundation for providing the URL for the video ‘The poison that waits?’. The authors also thank J. Stankus for preparing the original version of Fig. 1, and D. Konickova for preparing the original version of Fig.3.
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K.M., J.C.S., R.R., P.S., A.L., Y.U., R.S., L.T., S.B., G.R. and P.K. researched data for the manuscript and/or contributed to its conceptualization. J.C.S., C.C., P.S., A.L., Y.U., S.G.-R., R.M., R. Vodicka and S.B. substantially contributed to discussions of the article content. P.K., K.M., R.R., D.H., L.T. and K.K. wrote the manuscript. P.H., P.O., R. Vrtel, M.P., M.B., L.B., G.R. and M.S. undertook critical reading of the manuscript. Figures and Supplementary information were provided by P.S., D.H. and L.T. (Fig. 5), S.B. (Fig. 4), L.B., M.S. and K.M. (Fig. 1), R.R. (Fig. 2, part C) and A.L. All authors reviewed and edited the entire manuscript.
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The Poison that Waits?: https://vimeo.com/1621281
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Menšíková, K., Steele, J.C., Rosales, R. et al. Endemic parkinsonism: clusters, biology and clinical features. Nat Rev Neurol 19, 599–616 (2023). https://doi.org/10.1038/s41582-023-00866-3
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DOI: https://doi.org/10.1038/s41582-023-00866-3
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