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  • Review Article
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Endemic parkinsonism: clusters, biology and clinical features

Nature Reviews Neurology volume 19, pages 599–616 (2023)Cite this article

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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overlap in biological and clinical features of these exceptionally interesting diseases, this Review provides a historical reference text and offers current perspectives on each of the 10 phenotypes of endemic parkinsonism.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

  • 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.

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Fig. 1: Timeline of discoveries and important events related to endemic parkinsonism.
Fig. 2: Neuropathological features of Western Pacific and Oceanian clusters of endemic parkinsonism.
Fig. 3: Putative mechanisms of action of neurotoxic environmental compounds.
Fig. 4: Neuropathological features of Guadeloupe parkinsonism.
Fig. 5: Neuropathological features of atypical parkinsonism in Southeastern Moravia.

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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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Authors and Affiliations

  1. Department of Neurology and Clinical Neuroscience Center, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic

    Katerina Menšíková, Miroslav Strnad, Petr Hlustik, Pavel Otruba & Petr Kaňovský

  2. University Hospital, Olomouc, Czech Republic

    Katerina Menšíková, Lucie Tuckova, Dominik Hrabos, Kristyna Kolarikova, Radek Vodicka, Radek Vrtel, Miroslav Strnad, Petr Hlustik, Pavel Otruba, Martin Prochazka & Petr Kaňovský

  3. Independent Researcher, Bali, Indonesia

    John C. Steele

  4. Research Center for Health Sciences, Faculty of Medicine and Surgery, University of Santo Tomás, Manila, The Philippines

    Raymond Rosales

  5. St Luke’s Institute of Neuroscience, Metro, Manila, The Philippines

    Raymond Rosales

  6. Department of Neurology, Santa Maria University Hospital, Terni, Italy

    Carlo Colosimo

  7. Department of Neurology, School of Medicine, Oregon Institute of Occupational Health Sciences, Oregon Health & Science University, Portland, OR, USA

    Peter Spencer

  8. Départment de Neurologie, Centre Hospitalier Universitaire de la Guadeloupe, Pointe-á-Pitre, France

    Annie Lannuzel

  9. Department of Human Neurophysiology, Fukushima Medical University, Fukushima, Japan

    Yoshikazu Ugawa

  10. Department of Neurology, Kuwana City Medical Center, Kuwana, Japan

    Ryogen Sasaki

  11. Department of Neurology, Hospital General Universitario Gregorio Marañón, Madrid, Spain

    Santiago Giménez-Roldán

  12. Department of Pathology, 3rd Medical Faculty, Charles University and University Hospital Kralovske Vinohrady, Prague, Czech Republic

    Radoslav Matej

  13. Department of Pathology and Molecular Medicine, 3rd Medical Faculty, Charles University and Thomayer University Hospital, Prague, Czech Republic

    Radoslav Matej

  14. Department of Clinical and Molecular Pathology, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic

    Lucie Tuckova & Dominik Hrabos

  15. Department of Clinical and Molecular Genetics, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic

    Kristyna Kolarikova, Radek Vodicka, Radek Vrtel & Martin Prochazka

  16. Laboratory of Growth Regulators, Faculty of Science, Palacky University, Olomouc, Czech Republic

    Miroslav Strnad

  17. First Department of Neurology, Masaryk University Medical School, Brno, Czech Republic

    Martin Bares

  18. St Anne University Hospital, Brno, Czech Republic

    Martin Bares

  19. Département de Neuropathologie, Hôpital La Pitié — Salpêtrière, Paris, France

    Susana Boluda

  20. Lille Neuroscience & Cognition Research Centre, INSERM U1172, Lille, France

    Luc Buee

  21. Department of Neurology, Faculty of Medicine, Johannes Kepler University, Linz, Austria

    Gerhard Ransmayr

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  1. Katerina Menšíková
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Contributions

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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Correspondence to Petr Kaňovský.

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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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