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

Menšíková K, Rosales R, Colosimo C, Spencer P, Lannuzel A, Ugawa Y, Sasaki R, Giménez-Roldán S, Matej R, Tuckova L, Hrabos D, Kolarikova K, Vodicka R, Vrtel R, Strnad M, Hlustik P, Otruba P, Prochazka M, Bares M, Boluda S, Buee L, Ransmayr G, Kaňovský P.

Nat Rev Neurol. 2024 Mar;20(3):195-196. doi:10.1038/s41582-024-00938-y. PMID: 38336911.

11 Apr 2024

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

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