Paper reviewed: Okumiya K, Wada T, Fujisawa M, Ishine M, Garcia Del Saz E, Hirata Y, Kuzuhara S, Kokubo Y, Seguchi H, Sakamoto R, Manuaba I, Watofa P, Rantetampang AL, Matsubayashi K. Amyotrophic lateral sclerosis and parkinsonism in Papua, Indonesia: 2001-2012 survey results. BMJ Open. 2014 Apr 16;4(4):e004353. doi: 10.1136/bmjopen-2013-004353.
Web link. <link www.ncbi.nlm.nih.gov/pmc/articles/PMC3996815/>http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3996815/</link>
Reviewer’s/Authors’ affiliation.
1. Prof. Peter Spencer, Ph.D., FANA, FRCPath., Department of Neurology, Oregon Health& Science University, Portland, Oregon, USA. E-mail: spencer@ohsu.edu
2. Prof. Albert Ludolph, MD, Department of Neurology, University of Ulm, Germany. E-mail: <link albert.ludolph@rku.de>albert.ludolph@rku.de</link>
This is a significant clinical-epidemiological 2001-2013 survey of neurodegenerative disease among the Auyu and Jaqai linguistic groups of Papua, Indonesia who have experienced one of the highest incidences of amyotrophic lateral sclerosis (ALS) in the world. The ALS focus was first described in the 1960s by the late Carleton Gajdusek [PMID:7198738], associated with medicinal use of the seed of a neurotoxic plant (cycad) in the 1980s [PMID 2890883] and, in 1990, ALS prevalence in the disease epicenter was shown to be on the decline [PMID: 16092101]. As noted before, the present study found that ALS overlapped clinically with parkinsonism and cognitive impairment in many patients, especially males, a pattern akin to the cycad-associated ALS/parkinsonism-dementia complex described among Japanese residents of Kii Peninsula, Honshu, Japan and the Chamorro people of Guam, USA [PMID: 27050202]. The survey finds that ALS prevalence in Papua remains higher than the global average but has continued to decline, similar to earlier trends of declining ALS-PDC in Kii-Japan and Guam, where ALS has disappeared. Declining/disappearing ALS in three genetically disparate groups (Papua New Guinean, Japanese, Chamorro), coupled with the occasional acquisition of ALS among non-Chamorro immigrants to Guam, indicates a major, perhaps exclusive, environmental etiology [PMID: 27050202]. As Gajdusek noted, the culpable environmental factor(s) must be of natural origin because ALS among Papuan New Guineans existed before the introduction of man-made materials. Use of neurotoxic cycad seed for medicine (Papua, Guam, Kii-Japan) and food (Guam, Rota) is the most plausible but as-yet unproven environmental candidate while, surprisingly, putative genetic factors have yet to be abandoned by the authors. Identification of the culpable agent(s) and mechanism(s) of Western Pacific ALS-PDC has the potential to illuminate the etiology and pathogenesis of related neurodegenerative diseases worldwide.
Key Points:
1. The Papua focus of ALS, which often presents with parkinsonism (P) and cognitive impairment (D) in affected patients, remains more common among males and more highly prevalent than the global average, but the prevalence has declined over the past decades, similar to the temporal course of the ALS-PD Complex in Kii-Japan and Guam, where ALS has disappeared.
2. Declining/disappearing ALS in three genetically disparate groups (Papua New Guinean, Japanese, Chamorro), coupled with the occasional acquisition of ALS among non-Chamorro immigrants to Guam, indicates a major, perhaps exclusive, environmental etiology.
3. The culpable environmental factor(s) must be of natural origin because ALS among Papuan New Guineans existed before the introduction of manmade materials. Use of neurotoxic cycad seed for medicine (Papua, Guam, Kii-Japan) and food (Guam, Rota) is the most plausible but unproven candidate.
Additional Information: See the comments of the reviewers published in the BMC Open article.