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Guam ALS/Parkinsonism-Dementia: A Long-Latency Neurotoxic Disorder Caused by “Slow Toxin(s)” in Food?

Published online by Cambridge University Press:  05 January 2016

Peter S. Spencer
Peter S. Spencer*
Affiliation:
Institute of Neurotoxology, Departments of Neuroscience, Neurology, and Pathology, Albert Einstein College of Medicine, Bronx, N.Y.
*
Institute of Neurotoxicology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, N.Y., U.S.A. 10461
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Abstract:

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Parkinsonism (P) with progressive dementia (D) of the Alzheimer type is recognized as a clinical variant of a form of amyotrophic lateral sclerosis (ALS) that has occurred in high incidence among the Chamorro people of the islands of Guam and Rota in the Marianas chain of Micronesia. The declining annual incidence, upward shifting of the age of onset, narrowing of the sex ratio, and occurrence of the disease among non-Chamorros, point to a disappearing environmental causation peculiar to the traditional culture of these islands. Evidence is presented in support of the proposal that heavy use of certain toxic plants, notably cycads, a traditional source of food and medicine for the Chamorro people, plays an important etiological role. Clinical and epidemiological approaches are offered to test for a relationship between ALS/P-D and long-latency plant toxicity.

Type
Research Article
Information
Canadian Journal of Neurological Sciences , Volume 14 , Issue S3 , August 1987 , pp. 347 - 357
Copyright
Copyright © Canadian Neurological Sciences Federation 1987

References

REFERENCES

1.Spencer, PS, Schaumburg, HH.The pathogenesis of motor neuron disease: Perspectives from neurotoxicology. In: Rowland, LP, ed. Human Motor Neuron Diseases. New York: Raven Press, 1982; 249–266.Google ScholarPubMed
2.Spencer, PS, Schaumburg, HH, Cohn, DF, Seth, PK.Lathyrism: A useful model of primary lateral sclerosis. In: Rose, FC, ed. Research Progress in Motor Neurone Disease. Bath: Pitman, 1984; 312–317.Google Scholar
3.Spencer, PS, Schaumburg, HH.Lathyrism: A neurotoxic disease. Neurobeh Toxicol 1983; 5: 625–629.Google ScholarPubMed
4.Spencer, PS, Ludolph, A, Dwivedi, MP, et al. Lathyrism: Evidence for role of the neuroexcitatory amino acid BOAA. Lancet 1986; 2: 1066–1067.CrossRefGoogle ScholarPubMed
5.Ludolph, A, Hugon, J, Dwivedi, MP, et al. Studies on the aetiology and pathogenesis of motor neuron diseases. 1. Lathyrism: Clinical findings in established cases. Brain 1987; 110: 149–165.CrossRefGoogle ScholarPubMed
6.Whiting, MG.Toxicity of cycads. Econ Bot 1963; 17: 271–302.CrossRefGoogle Scholar
7.Lyon Arboretum: Transcripts of four conferences (1st, 2nd, 4th and 5th) on the toxicity of cycads. New York, Third World Medical Research Foundation (in press). Proceedings of the Third Conference on the Toxicity of Cycads. Fed Proc 1964; 23: 1337–1387. Sixth International Cycad Conference. Fed Proc 1972; 31: 1465–1538.Google Scholar
8.Kurland, LT.An appraisal of the neurotoxicity of cycad and the etiology of amyotrophic lateral sclerosis on Guam. Fed Proc 1972; 31: 1540–1542.Google ScholarPubMed
9.Kurland, LT, Molgaard, CA.Guamanian ALS: Hereditary or acquired? In: Rowland, LP, ed. Human Motor Neuron Diseases. New York: Raven Press, 1982: 165–171.Google Scholar
10.Nunn, PB, Seelig, M, Zagoren, JC, Spencer, PS.Stereospecific acute neuronotoxicity of “uncommon” plant amino acids linked to human motor-system diseases. Brain Res 1987; 410: 375–379.CrossRefGoogle ScholarPubMed
11.Ross, SM, Seelig, M, Spencer, PS.Specific antagonism of excitotoxic action of “uncommon” amino acids assayed in organotypic mouse cortical cultures. Brain Res (in press).Google Scholar
12.Spencer, PS, Ross, SM, Nunn, PB, et al. Detection and characteriza-tion of plant-derived amino acid motorsystem toxins in mouse CNS culture. In: Shahar, A, ed. Model Systems in Neurotoxicology — Alternative Approaches to Animal Testing. New York, Alan R. Liss (in press).Google Scholar
13.Spencer, PS, Nunn, PB, Hugon, J, et al. Motor neurone disease on Guam: Possible role of a food neurotoxin. Lancet 1986; 1: 965.CrossRefGoogle ScholarPubMed
14.Spencer, PS, Hugon, J, Ludolph, A, et al. Discovery and partial characterization of primate motor-system toxins. In: Bock, G, O’Connor, M, eds. Selective Neuronal Death. Ciba Foundation Symposium #126. Chichester, Wiley 1987: 221–238.Google ScholarPubMed
15.Spencer, PS, Nunn, PB, Hugon, J, et al. Guam amyotrophic lateral sclerosis-parkinsonism-dementia to a plant excitant neurotoxin. Science (in press).Google Scholar
16.Hirano, A, Kurland, LT, Krooth, RS, Lessell, S.Parkinsonism- dementia complex, an endemic disease on the island of Guam. I. Clinical features. Brain 1961; 84: 642–661.CrossRefGoogle ScholarPubMed
17.Hirano, A, Malamud, N, Kurland, LT.Parkinsonism-dementia complex, an endemic disease on the island of Guam. II. Pathological features. Brain 1961; 84: 662–679.CrossRefGoogle ScholarPubMed
18.Elizan, TS, Hirano, A, Abrams, BM, et al. Amyotrophic lateral sclerosis and parkinsonism-dementia complex of Guam. Neurological réévaluation. Arch Neurol 1966; 14: 356–368.CrossRefGoogle ScholarPubMed
19.Reed, DM, Brody, JA.Amyotrophic lateral sclerosis and parkinsonism-dementia on Guam, 1945–1972.1. Descriptive epidemiology. Am J Epidemiol 1975; 101: 287–301.CrossRefGoogle ScholarPubMed
20.Chen, K-M, Yase, Y.Parkinsonism-dementia, neurofibrillary tangles, and trace elements in the Western Pacific. In: Hutton, JT, Kenny, AD, eds. Senile Dementia of the Alzheimer Type. New York, Alan R. Liss 1985: 153–173.Google Scholar
21.Yanagihara, RT, Garruto, RM, Gajdusek, DC.Epidemiological sur-veillance of amyotrophic lateral sclerosis and parkinsonism-dementia in the Commonwealth of the Northern Mariana Islands. Ann Neurol 1983; 13: 79–86.CrossRefGoogle Scholar
22.Garruto, RM, Gajdusek, DC, Chen, K-M.Amyotrophic lateral scle-rosis and parkinsonism-dementia among Filipino migrants to Guam. Ann Neurol 1981; 10: 341–350.CrossRefGoogle Scholar
23.Brody, JA, Edgar, AH, Gellapse, MM.Amyotrophic lateral sclerosis: No increase among U.S. construction workers in Guam. J Am Med Assoc 1979; 240: 551–552.CrossRefGoogle Scholar
24.Garruto, RM, Gajdusek, DC, Chen, K-M.Amyotrophic lateral scle-rosis among Chamorro migrants from Guam. Ann Neurol 1980; 8: 612–619.CrossRefGoogle Scholar
25.Anderson, FH, Richardson, EP, Okazaki, H, Brody, JA.Neurofibril-lary degeneration on Guam: frequency in Chamorros and non-Chamorros with no known neurologic disease. Brain 1975; 102: 65–77.CrossRefGoogle Scholar
26.Chen, K-M.Neurofibrillary changes on Guam. Arch Neurol 1981; 38: 16–18.CrossRefGoogle ScholarPubMed
27.Plato, CC, Garruto, RM, Fox, KM, Gajdusek, DC.Amyotrophic lateral sclerosis and parkinsonism-dementia on Guam: A 25-year prospective case-control study. Am J Epidemiol 1986; 124:643–656.CrossRefGoogle ScholarPubMed
28.Gibbs, CJ Jr, Gajdusek, DC.An update on longterm in vivo and in vitro studies designed to identify a virus as the cause of amyotrophic lateral sclerosis, parkinsonism-dementia, and Parkinson’s disease. In: Rowland, LP, ed. Human Motor Neuron Diseases. New York, Raven Press 1982: 343–353.Google ScholarPubMed
29.Garruto, RM, Yanagihara, R, Gajdusek, DC.Disappearance of high-incidence amyotrophic lateral sclerosis and parkinsonism-dementia on Guam. Neurology 1985; 35: 193–198.CrossRefGoogle ScholarPubMed
30.Mulder, DW, Kurland, LT, Iriarte, LLG.Neurologic diseases on the island of Guam. US Armed Forces Med J 1954; 5: 1724–1739.Google ScholarPubMed
31.Zimmerman, HM.Monthly report to medical officer in command, US Naval Med Res Unit #2, June 1.Google Scholar
32.Arnold, A, Edgren, DC, Palladino, VS.Amyotrophic lateral sclerosis. Fifty cases observed on Guam. J Nerv Ment Dis 1953; 117: 135–139.CrossRefGoogle ScholarPubMed
33.Koerner, DR.Amyotrophic lateral sclerosis on Guam: A clinical study and review of the literature. Ann Int Med 1952; 37:1204–1220.Google Scholar
34.Okaya, N.Beryo gamu shimajima min chamoro-zoku (mikuronesyajin)ni okeru shisen mahi serirei. (A case of paralysis agitans in a Chamorro (Micronesian) from Guam, US Territory). Tokyo Med J 1936; 2997: 2517–2518. See also Yase, Y, Chen, K-M, Brody, JA, Toyokura, Y. An historical note on the Parkinsonism-dementia complex of Guam. Neurol Med (Tokyo) 1978; 8:583–589.Google Scholar
35.Malamud, N, Hirano, A, Kurland, LT.Pathoanatomic changes in amyotrophic lateral sclerosis on Guam. Arch Neurol 1961; 15: 401–415.CrossRefGoogle Scholar
36.Lessell, S, Hirano, A, Torres, J, Kurland, LT.Parkinsonism-dementia complex. Epidemiological considerations in the Chamorros of the Mariana islands and California. Arch Neurol 1962;7:377–385.CrossRefGoogle Scholar
37.Kurland, LT.Epidemiological investigations of neurological disor-ders in the Mariana islands. In: Pemberton, J, ed. Epidemiology Reports on Research and Teaching. Oxford, University Press 1963: 219–223.Google Scholar
38.Kurland, LT.An appraisal of epidemiologic and genetic develop-ments in amyotrophic lateral sclerosis and Kuru. Proc Vth Int Congr Neurpathol. Amsterdam: Excerpta Medica 1965; 100: 182–189.Google Scholar
39.Kurland, LT, Mulder, DW.Overview of motor neuron disease. Proc Int Meeting Motor Neuron Diseases, Bangalore 1984.Google Scholar
40.Yanagihara, R, Garruto, RM, Gajdusek, DC, et al. Calcium and vitamin D metabolism in Guamanian Chamorros with amyotrophic lateral sclerosis and parkinsonism-dementia. Ann Neurol 1984; 15: 42–47.CrossRefGoogle ScholarPubMed
41.Yase, Y.The role of aluminum on CNS degeneration with interac-tion of calcium. Neurotox 1980; 1: 101–109.Google Scholar
42.Yase, Y.The pathogenesis of amyotrophic lateral sclerosis. Lancet 1972; 2: 292–296.CrossRefGoogle ScholarPubMed
43.Rodgers-Johnson, P, Garruto, RM, Yanagihara, R, et al. Amyotro-phic lateral sclerosis and parkinsonism-dementia on Guam: A 30-year evaluation of clinical and neuropathological trends. Neurology 1986;36: 7–13.CrossRefGoogle ScholarPubMed
44.Perl, DP, Gajdusek, DC, Garruto, RM, et al. Intraneuronal aluminum accumulation in amyotrophic lateral sclerosis and parkinsonism-dementia of Guam. Science 1982; 217: 1053–1055.CrossRefGoogle ScholarPubMed
45.Garruto, RM, Swyt, TC, Yanagihara, R, et al. Intraneuronal co-localization of silicon with calcium and aluminum in amyotrophic lateral sclerosis and parkinsonism with dementia of Guam. New Engl J Med 1986;315:711–712.Google ScholarPubMed
46.Zolan, WJ, Ellis-Neill, L.Concentrations of aluminum, manganese, iron, and calcium in four southern Guam rivers. University of Guam, Agàna Technical Report #64, June, 1986.Google Scholar
47.Kond, oK.Population dynamics of motor neuron disease./«:Tsubaki, T, Toyokura, Y, eds. Amyotrophic Lateral Sclerosis. Baltimore: University Park Press 1979: 61–103.Google Scholar
48.Fullmer, HM, Siedler, HD, Krooth, RS, Kurland, LT.A cutaneous disorder of connective tissue in amyotrophic lateral sclerosis. A histochemical study. Neurology 1960; 10: 707–724.CrossRefGoogle ScholarPubMed
49.Krooth, RS, Macklin, MT, Hilbish, TF.Diaphysial aclasis (multiple exostoses) on Guam. Am J Hum Genet 1961; 13: 340–347.Google ScholarPubMed
50.Spencer, PS, Dastur, DK.Neurolathyrism and neurocycadism. In: Dastur, DK, Shahani, M, Bharucha, EP, eds. Neurological Sciences – An Overview of Current Problems. Section VI. Tropical Neurology and Neurotoxicology, Interprint, New Delhi (in press).Google Scholar
51.Whiting, MG.Food practices in ALS foci in Japan, the Marianas, and New Guinea. Fed Proc 1964; 23: 1343–1345.Google ScholarPubMed
52.Adiga, PR, Rao, SLN, Sarma, PS.Some structural features and neurotoxic action of a compound from Lathyrus sativus seeds. Curr Sci 1963; 32: 153.Google Scholar
53.Murti, VVS, Seshadri, TR, Venkitasubramanian, TA.Neurotoxic compounds of the seeds of Lathyrus sativus. Phytochem 1964; 3: 73–78.CrossRefGoogle Scholar
54.Bell, EA.Relevance of biochemical taxonomy to the problem of lathyrism Nature (Lond) 1964; 203: 378–380.Google Scholar
55.Bell, EA, in discussion of Polsky Fl, Nunn PB, Bell EA. Distribu-tion and toxicity of α-aminoβ-methylaminopropionic acid. Fed Proc 1972; 31: 1475.Google Scholar
56.Mehta, T, Parker, AJ, Cusick, PK, et al. The Lathyrus sativus neurotoxin: Resistance of the squirrel monkey to prolonged oral high doses. Toxicol Appl Pharmacol 1983; 69: 480–484.CrossRefGoogle ScholarPubMed
57.Laqueur, GL, Mickelsen, O, Whiting, MG, Kurland, LT.Carcino-genic properties of nuts from Cycas circinalis L. indigenous to Guam. J Natl Cancer Inst 1963; 31: 919–951.Google Scholar
58.Yang, MG, Mickelsen, O, Campbell, ME, et al. Cycad flour used by Guamaniams: Effects produced in rats by long-term feeding. J Nutr 1966; 90: 153–156.CrossRefGoogle ScholarPubMed
59.Dastur, KD.Cycad toxicity in monkeys: clinical, pathological, and biochemical aspects. Fed Proc 1964; 23: 1368–1369.Google ScholarPubMed
60.Polsky, FI, Nunn, PB, Bell, EA.Distribution and toxicity of a-amino-β-methylaminopropionic acid. Fed Proc 1972; 31: 1473–1475.Google ScholarPubMed
61.Louw, WK, Oelofsen, W.Carcinogenic and neurotoxic components in the cycad Encephalartosaltensteinii Lehm. (Family Zamiacae). Toxicon 1975; 13: 447–452.CrossRefGoogle ScholarPubMed
62.Cohn, DF, Streifler, M.Human neurolathyrism: a follow-up of 200 patients. Part 1: Clinical investigation. Arch Suisses Neurol Psychiat 1981; 128: 151–156.Google ScholarPubMed
63.Zagoren, JC, Seelig, M, Roy, DN, et al. Pathological changes in spinal cord induced by Lathyrus neurotoxin (β-Ν-oxalylamino-L-alanine) in vitro. J Neuropathol Exp Neurol 1985; 44: 124.Google Scholar
64.Olney, JW, Misra, CH, Rhee, V.Brain and retinal damage from Lathyrus excitotoxin, β-Ν-oxalyl-L-a, β-diaminopropionic acid. Nature, Lond 1976; 264: 659–661.CrossRefGoogle ScholarPubMed
65.Ross, SM, Spencer, PS.Specific antagonism of behavioral action of “uncommon” amino acids linked to motor-system diseases. Synapse 1987; 1: 248–253.CrossRefGoogle ScholarPubMed
66.Hirano, A, Iwata, M.Pathology of motor neurons with special reference to amyotrophic lateral sclerosis and related diseases. In: Tsubaki, T, Toyokura, Y, eds. Amyotrophic Lateral Sclerosis. Baltimore: Univ Park Press 1979: 107–133.Google Scholar
67.Prineas, J, Spencer, PS.Pathology of the nerve cell body in disor-ders of the peripheral nervous systems. In: Dyck, PJ, Thomas, PK, Lambert, EH, eds. Peripheral Neuropathy. Philadelphia: WB Saunders 1975; 253–295.Google Scholar
68.Calne, DB, Eisen, A, Mcgeer, E, Spencer, PS.Alzheimer’s disease, Parkinson’s disease, and motorneurone disease: abiotrop[h]ic interaction between ageing and environment. Lancet 1986; 11: 1067–1069.CrossRefGoogle Scholar
69.Lessell, A, Torres, JM, Kurland, LT.Seizure disorder in a Guamanian village. Arch Neurol 1962; 7: 37–44.CrossRefGoogle Scholar
70.Mathai, KV, Dunn, DP, Kurland, LT, Reeder, FA.Convulsive disor-ders in the Mariana islands. Epilepsia 1968; 9: 77–85.CrossRefGoogle Scholar
71.Stanhope, JM, Brody, JA, Brink, E.Convulsions among the Chamorropeople of Guam, Mariana islands. 1. Seizure disorders. Am J Epidemiol 1972; 95: 292–298.CrossRefGoogle Scholar
72.Stanhope, JM, Brody, JA, Brink, E, Morris, CE.Convulsions among the Chamorro people of Guam, Mariana islands. II. Febrile convulsions. Am J Epidemiol 1972; 95: 299–304.CrossRefGoogle ScholarPubMed
73.Huston, JW, Lingenfelder, J, Mulder, D, Kurland, LT.Pregnancy complicated by amyotrophic lateral sclerosis. Am J Obst Gynecol 1956; 72: 93–99.CrossRefGoogle ScholarPubMed
74.Jones, M, Yang, , Mickelsen, O.Effects of methylazoxymethanol glucoside and methylazoxymethanol acetate on the cerebellum of the postnatal Swiss albino mouse. Fed Proc 1972,31:1508–1511.Google ScholarPubMed
75.Mickelsen, O, Campbell, E, Yang, M, et al. Studies with cycad. Fed Proc 1964; 23: 1363–1365.Google ScholarPubMed
76.Plato, C, Greulich, WW, Garruto, , et al. Cortical bone loss and mea-surements of the second metacarpal bone. II. Hypodense bone in postwar Guamanian children. Am J Phys Anthropol 1984; 63: 57–63.CrossRefGoogle Scholar
77.Kurland, LT.Introductory remarks. Proc Third Cycad Conf Fed Proc 1964; 23: 1337–1339.Google ScholarPubMed
78.Laqueur, GL. in discussion, Birdsey, MR.A brief description of the cycads. Fed Proc 1972; 1467–1469.Google Scholar
79.Chen, K-M, Uebayashi, Y.Amyotrophic lateral sclerosis and parkinsonism-dementia of Guam: An update. In: Chen, K-M, Yase, Y, eds. Amyotrophic Lateral Sclerosis in Asia and Oceania. Taiwan: National University 1984: 199–240.Google Scholar
80.Yen, SSC.Abnormal carbohydrate metabolism and pregnancy. A study among pregnant Guamanian women. Am J Obst Gynecol 1964; 90: 468–473.CrossRefGoogle ScholarPubMed
81.Hirono, I.Carcinogenicity and neurotoxicity of cycasin with spe-cial reference to species differences. Fed Proc 1972; 31:1943–1947.Google Scholar
82.Olney, JW.Excitotoxic mechanisms of neurotoxicity. In: Spencer, PS, Schaumburg, HH, eds. Experimental and Clinical Neurotoxicology. Baltimore: Williams and Wilkins, 1980; 272–294.Google Scholar
83.Reed, D, Plato, C, Elizan, T, Kurland, LT.The amyotrophic lateral sclerosis-parkinsonism-dementia complex: a 10-year follow-up on Guam Epidemiological Studies. Am J Epidemiol 1966; 83: 54–73.CrossRefGoogle Scholar
84.Ministry of Health, Mozambique. Mantakassa: An epidemic of spastic paraparesis associated with chronic intoxication in a cassava staple area of Mozambique. 1. Epidemiological and clinical and laboratory findings in patients. Bull World Health Organization 1984; 63: 477–484.Google Scholar
85.Osuntokun, BO.Cassava diet, chronic cyanide intoxication and neuropathy in Nigerian Africans. World Rev Nutri Dietet 1981; 36: 141–173.CrossRefGoogle ScholarPubMed
86.Chandra, B.Some aspects of amyotrophic lateral sclerosis in Surabaya.In: Chen, K-M, Yase, Y, eds. Amyotrophic Lateral Sclerosis in Asia and Oceania. Taiwan: National University 1984; 141–144.Google Scholar
87.Kiloh, LG, Cawte, JE.A neurological ethnic-geographic isolate on Groóte Eylandt. In: Chen, K-M, Yase, Y, eds. Amyotrophic Lateral Sclerosis in Asia and Oceania. Taiwan: National University, 1984; 141–144.Google Scholar
88.Reed, D, Labarthe, D, Chen, K-M, Stallones, R.A cohort study of amyotrophic lateral sclerosis and parkinsonism-dementia on Guam and Rota. Am J Epidemiol 1987; 125: 92–100.CrossRefGoogle ScholarPubMed