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Reply to: Questioning the cycad theory of Kii ALS–PDC causation

Nature Reviews Neurology volume 20, pages 195–196 (2024)Cite this article

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We read with great interest the Correspondence to our recent Review (Menšíková, K. et al. Endemic parkinsonism: clusters, biology and clinical features. Nat. Rev. Neurol. 19, 599–616 (2023)1) by Kokubo and colleagues (Kokubo, Y., Morimoto, S. & Yoshida, M. Questioning the cycad theory of Kii ALS–PDC causation. Nat. Rev. Neurol. https://doi.org/10.1038/s41582-024-00936-0 (2024)2). We are aware that Kokubo — together with the late S. Kuzuhara — systematically studied amyotrophic lateral sclerosis–parkinsonism–dementia complex (ALS–PDC) on the Kii Peninsula for more than 30 years. They authored and co-authored numerous papers about this endemic disease, some of them with one of us (R.S.). We therefore considered the comments raised by Kokubo et al. carefully, and here we respond to the questions that they have raised.

Kokubo et al. state that the use of cycad seed in herbal and folk medicine, and as a tonic in children, is very rare. However, in the northeastern Kii (Hohara) focus of ALS–PDC, the seed of Cycas revoluta was prescribed throughout the 1980s by kitoshi (folk medicine practitioners) and dispensed by local pharmacies for the oral treatment of various ailments, including diarrhoea, dysmenorrhoea, gonorrhoea, tuberculosis and neuralgia, in accordance with published guidance3. In 1986, one of us (P.S.) personally met with a kitoshi in Owase, Mie prefecture, who prescribed cycad seed (sotetsu) for a fictional gastrointestinal problem; a local pharmacy that dispensed sotetsu seed for medicinal purposes is depicted in the BBC video The Poison That Waits. Importantly, older patients with ALS–PDC might not remember using this medicine or being dosed with sotetsu tonic during infancy, another local practice that is documented in the BBC video.

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References

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Acknowledgements

The authors remember J. C. Steele (1934–2022).

Author information

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

    Raymond Rosales

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

    Raymond Rosales

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

    Carlo Colosimo

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

    Peter Spencer

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

    Annie Lannuzel

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

    Yoshikazu Ugawa

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

    Ryogen Sasaki

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

    Santiago Giménez-Roldán

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

    Radoslav Matej

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

    Radoslav Matej

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

    Lucie Tuckova & Dominik Hrabos

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

    Kristyna Kolarikova, Radek Vodicka, Radek Vrtel & Martin Prochazka

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

    Miroslav Strnad

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

    Martin Bares

  17. St Anne University Hospital, Brno, Czech Republic

    Martin Bares

  18. Département de Neuropathologie, Hôpital La Pitié – Salpêtrière, Paris, France

    Susana Boluda

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

    Luc Buee

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

    Gerhard Ransmayr

Authors
  1. Katerina Menšíková
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  2. Raymond Rosales
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  22. Gerhard Ransmayr
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  23. Petr Kaňovský
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Corresponding author

Correspondence to Petr Kaňovský.

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The Poison that Waits: https://vimeo.com/1621281

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Menšíková, K., Rosales, R., Colosimo, C. et al. Reply to: Questioning the cycad theory of Kii ALS–PDC causation. Nat Rev Neurol 20, 195–196 (2024). https://doi.org/10.1038/s41582-024-00938-y

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