Back to Journals » Eye and Brain » Volume 12

Etiology of Retinal and Cerebellar Pathology in Western Pacific Amyotrophic Lateral Sclerosis and Parkinsonism-Dementia Complex

Authors Spencer PS

Received 2 May 2020

Accepted for publication 20 June 2020

Published 16 July 2020 Volume 2020:12 Pages 97—104


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Professor Margaret Wong-Riley

Peter S Spencer

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

Correspondence: Peter S Spencer
Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239 Tel +1 503 209-0986

Purpose: To reexamine the etiology of a unique retinal pathology (linear and vermiform sub-retinal tubular structures) described among subjects with and without neurodegenerative disease in former high-incidence foci of Western Pacific amyotrophic lateral sclerosis and parkinsonism-dementia complex (ALS/PDC) in Guam (USA) and the Kii peninsula of Honshu island (Japan).
Methods: Analysis of published and unpublished reports of 1) ALS/PDC and the retinal and cerebellar pathology associated therewith and 2) exogenous neurotoxic factors associated with ALS/PDC and the developing retina and cerebellum.
Results: ALS/PDC retinal and cerebellar pathology matches persistent retinal and cerebellar dysplasia found in laboratory animals given single in utero or postnatal systemic treatment with cycasin, the principal neurotoxic component in the seed of cycad plants traditionally used for food (Guam) or oral medicine (Kii-Japan), both of which have been linked to the human neurodegenerative disease.
Conclusion: ALS/PDC-associated retinal and cerebellar dysplasia could arise from in utero exposure to methylazoxymethanol, the genotoxic metabolite of cycasin that results from maternal ingestion of this azoxyglucoside. These results support the environmental toxic etiology of retinal and brain pathology in ALS/PDC.

Keywords: amyotrophic lateral sclerosis, cycad, DNA damage, Guam, methylazoxymethanol, photoreceptor, retinal development, retinal dysplasia, retinal epitheliopathy, rosettes

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]