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. 1979 Dec;42(12):1073–1083. doi: 10.1136/jnnp.42.12.1073

Neurotoxicity of halogenated hydroxyquinolines: clinical analysis of cases reported outside Japan.

G Baumgartner, M J Gawel, H E Kaeser, C A Pallis, F C Rose, H H Schaumburg, P K Thomas, N H Wadia
PMCID: PMC490422  PMID: 230316

Abstract

An analysis is presented of 220 cases of possible neurotoxic reactions to halogenated hydroxyquinolines reported from outside Japan. In 80 cases insufficient information was available for adequate comment and in 29 a relationship to the administration of clioquinol could be excluded. Of the remainder, a relationship to clioquinol was considered probable in 42 and possible in 69 cases. In six of the probable cases the neurological disturbance consisted of an acute reversible encephalopathy usually related to the ingestion of a high dose of clioquinol over a short period. The most common manifestation, observed in 15 further cases, was isolated optic atrophy. This was most frequently found in children, many of whom had received clioquinol as treatment for acrodermatitis enteropathica. In the remaining cases, a combination of myelopathy, visual disturbance, and peripheral neuropathy was the most common manifestation. Isolated myelopathy or peripheral neuropathy, or these manifestations occurring together, were infrequent. The onset of all manifestations (except toxic encephalopathy) was usually subacute, with subsequent partial recovery. Older subjects tended to display more side effects. The full syndrome of subacute myelo-optic neuropathy was more frequent in women, but they tended to have taken greater quantities of the drug.

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Selected References

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  1. Aguilera Diaz L. F. Un nouveau symptôme dans l'acrodermatite entéropathique: la démarche ataxique. Bull Soc Fr Dermatol Syphiligr. 1971;78(3):259–260. [PubMed] [Google Scholar]
  2. Ando K., Sobue I. [Abdominal and neurological symptoms of subacute myeloneuropathy with abdominal symptoms]. Saishin Igaku. 1969 Dec;24(12):2440–2450. [PubMed] [Google Scholar]
  3. Berggren L., Hansson O. Absorption of intestinal antiseptics derived from 8-hydroxyquinolines. Clin Pharmacol Ther. 1968 Jan-Feb;9(1):67–70. doi: 10.1002/cpt19689167. [DOI] [PubMed] [Google Scholar]
  4. Billson F. H., Reich J., Hopkins I. J. Visual failure in a patient with ulcerative colitis treated by clioquinol. Lancet. 1972 May 6;1(7758):1015–1016. doi: 10.1016/s0140-6736(72)91186-5. [DOI] [PubMed] [Google Scholar]
  5. Cambier J., Masson M., Berkman N., Dairou R. Neruopathie sensitive et névrite optique après absorption prolongée de chloroidoquinone. Nouv Presse Med. 1972 Aug 26;1(30):1991–1992. [PubMed] [Google Scholar]
  6. Carr W. G., Bowen R. A., Horner F. A. Iodochlorhydroxyquin and optic nerve damage. Can Med Assoc J. 1977 Feb 5;116(3):251–251. [PMC free article] [PubMed] [Google Scholar]
  7. Castaiggne P., Rondot P., Lenoel Y., Ribadeau Dumas J. L., Autret A. Myélopathie sévère, neuropathie périphérique et névrite optique survenues au cours d'un traitement par la chloroiodoquine (clioquinol. Therapie. 1973 Mar-Apr;28(2):393–400. [PubMed] [Google Scholar]
  8. DILLAHA C. J., LORINCZ A. L., AAVIK O. R. Acrodermatitis enteropathica; review of the literature and report of a case successfully treated with diodoquin. J Am Med Assoc. 1953 Jun 6;152(6):509–512. doi: 10.1001/jama.1953.03690060025009. [DOI] [PubMed] [Google Scholar]
  9. Dahl K. B. Acrodermatitis enteropathica behandlet med jodkloroksykinolin. Ugeskr Laeger. 1974 Jan 28;136(5):263–265. [PubMed] [Google Scholar]
  10. Danis P. Nevrite optique et clioquinol. Bull Soc Belge Ophtalmol. 1971 Nov 28;159:671–675. [PubMed] [Google Scholar]
  11. Ferrier T. M., Eadie M. J. Clioquinol encephalopathy. Med J Aust. 1973 Dec 1;2(22):1008–1009. doi: 10.5694/j.1326-5377.1973.tb129907.x. [DOI] [PubMed] [Google Scholar]
  12. Fleisher D. I., Hepler R. S., Landau J. W. Blindness during diiodohydroxyquin (Diodoquin) therapy: a case report. Pediatrics. 1974 Jul;54(1):106–108. [PubMed] [Google Scholar]
  13. Freeman C. P., Basson J. V., Crighton A. Double-blind controlled trail of electroconvulsive therapy (E.C.T.) and simulated E.C.T. in depressive illness. Lancet. 1978 Apr 8;1(8067):738–740. doi: 10.1016/s0140-6736(78)90857-7. [DOI] [PubMed] [Google Scholar]
  14. Froissart M., Morcamp D., Mizon J. P. Myélo-neuropathie sensitivo-motrice après absorption de chloroiodoquinone. Nouv Presse Med. 1976 Mar 27;5(13):863–863. [PubMed] [Google Scholar]
  15. GHOLZ L. M., ARONS W. L. PROPHYLAXIS AND THERAPY OF AMEBIASIS AND SHIGELLOSIS WITH IODOCHLORHYDROXYQUIN. Am J Trop Med Hyg. 1964 May;13:396–401. doi: 10.4269/ajtmh.1964.13.396. [DOI] [PubMed] [Google Scholar]
  16. GHOLZ L. M. Long term prophylactic control of amebiasis and shigellosis. Am J Trop Med Hyg. 1962 Jul;11:452–454. doi: 10.4269/ajtmh.1962.11.452. [DOI] [PubMed] [Google Scholar]
  17. Garcia-Perez A., Castro C., Franco A., Escribano R. A case of optic atrophy possibly induced by quinoline in acrodermatitis enteropathica. Br J Dermatol. 1974 Apr;90(4):453–455. doi: 10.1111/j.1365-2133.1974.tb06433.x. [DOI] [PubMed] [Google Scholar]
  18. Gendre J. P., Barbanel C., Degos J. D., Le Quintrec Y. Neuropathie sensitivomotrice grave. Un cas, après absorption de clioquinol, chez un insuffisant rénal. Nouv Presse Med. 1974 Nov 2;3(37):2395–2398. [PubMed] [Google Scholar]
  19. Grenier B., Rolland J. C., Kiffer A., Maupas P. Myéloradiculonévrites subaiguës et chloroiodoxyquinoléine: intoxication ou pathologie virale. Nouv Presse Med. 1973 Apr;2(16):1076–1076. [PubMed] [Google Scholar]
  20. Kaeser H. E., Wüthrich R. Zur Frage der Neurotoxizität der Oxychinoline. Dtsch Med Wochenschr. 1970 Aug 14;95(33):1685–1688. doi: 10.1055/s-0028-1108711. [DOI] [PubMed] [Google Scholar]
  21. Kean B. H. Subacute myelo-optic neuropathy: a probable case in the United States. JAMA. 1972 Apr 10;220(2):243–244. [PubMed] [Google Scholar]
  22. Kjaersgaard K. Amnesia after clioquinol. Lancet. 1971 Nov 13;2(7733):1086–1086. doi: 10.1016/s0140-6736(71)90397-7. [DOI] [PubMed] [Google Scholar]
  23. Kono R. Subacute myelo-optico-neuropathy, a new neurological disease prevailing in Japan. Jpn J Med Sci Biol. 1971 Aug;24(4):195–216. doi: 10.7883/yoken1952.24.195. [DOI] [PubMed] [Google Scholar]
  24. Laterre E. C., Stevens A., Goffin L., Velghe L. Myélopathie subaiquë (SMON) après absorption d'hydrozquinoléines. Nouv Presse Med. 1973 Oct 27;2(38):2550–2550. [PubMed] [Google Scholar]
  25. Leopold I. H. Zinc deficiency and visual impairment? Am J Ophthalmol. 1978 Jun;85(6):871–875. doi: 10.1016/s0002-9394(14)78122-x. [DOI] [PubMed] [Google Scholar]
  26. Mamoli B., Thaler A., Heilig P., Siakos G. Subakute Myelo-Optico-Neuropathie (S.M.O.N.) nach Clioquinolmedikation. J Neurol. 1975 Jun 9;209(2):139–147. doi: 10.1007/BF00314607. [DOI] [PubMed] [Google Scholar]
  27. McEwen L. M., Constantinopoulos P. The use of a dietary and antibacterial regime in the management of intrinsic allergy. Ann Allergy. 1970 Jun;28(6):256–266. [PubMed] [Google Scholar]
  28. McEwen L. M. Neuropathy after clioquinol. Br Med J. 1971 Oct 16;4(5780):169–170. doi: 10.1136/bmj.4.5780.169-b. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Meade T. W. Subacute myelo-optic neuropathy and clioquinol. An epidemiological case-history for diagnosis. Br J Prev Soc Med. 1975 Sep;29(3):157–169. doi: 10.1136/jech.29.3.157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Moynahan E. J., Barnes P. M. Zinc deficiency and a synthetic diet for lactose intolerance. Lancet. 1973 Mar 24;1(7804):676–677. doi: 10.1016/s0140-6736(73)92253-8. [DOI] [PubMed] [Google Scholar]
  31. Osterman P. O. Myelopathy after clioquinol treatment. Lancet. 1971 Sep 4;2(7723):544–544. doi: 10.1016/s0140-6736(71)90460-0. [DOI] [PubMed] [Google Scholar]
  32. Otte G., De Coster W., Thiery E., De Reuck J., Vander eecken H. Subacute myelo-optic neuropathy. A toxic or a viral etiology? Acta Neurol Belg. 1976;76(5-6):331–334. [PubMed] [Google Scholar]
  33. Otte G., de Coster W., Thiery E., de Reuck J., vander Eecken H. Ultrastructural study of a muscle biopsy from a patient with subacute myelo-optic neuropathy. J Neurol. 1977 May 13;215(2):91–102. [PubMed] [Google Scholar]
  34. Pannekoek J. H. Neurotoxische verschijnselen na clioquinol (Enterovioform. Ned Tijdschr Geneeskd. 1972 Sep 2;116(36):1611–1615. [PubMed] [Google Scholar]
  35. Papuziński M., Wilmowska-Pietruszyńska A. Powikłania neurologiczne w przebiegu leczenia acrodermatitis enteropathica pochodnymi oxychinoliny. Pediatr Pol. 1974 Nov;49(11):1393–1397. [PubMed] [Google Scholar]
  36. Pedersen K. K., Christiansen N. Akut og kronisk kliokinolintoksikation. Ugeskr Laeger. 1972 Jul 17;134(29):1526–1528. [PubMed] [Google Scholar]
  37. Püschner H., Fankhauser R. Neuropathologische Befunde bei experimenteller Vioform-Vergiftung der weissen Maus. Schweiz Arch Tierheilkd. 1969 Jul;111(7):371–379. [PubMed] [Google Scholar]
  38. Reich H. Acrodermatitis enteeropathica: Gefahr arzneimittelbedingter Erblindung. Klin Wochenschr. 1973 Oct 15;51(20):1024–1024. doi: 10.1007/BF01468295. [DOI] [PubMed] [Google Scholar]
  39. Reich J. A., Billson F. A. Toxic optic neuritis. Clioquinol ingestion in a child. Med J Aust. 1973 Sep 22;2(12):593–595. [PubMed] [Google Scholar]
  40. Richard Sydney Allison. Lancet. 1978 May 20;1(8073):1108–1109. [PubMed] [Google Scholar]
  41. Romaine R. A., Lachman A. B. Letter: Acrodermatitis enteropathica-like clinical findings in two children. Arch Dermatol. 1974 Jan;109(1):96–97. [PubMed] [Google Scholar]
  42. Selby G. Subacute myelo-optic neuropathy in Australia. Lancet. 1972 Jan 15;1(7742):123–125. doi: 10.1016/s0140-6736(72)90682-4. [DOI] [PubMed] [Google Scholar]
  43. Shigematsu I. Subacute myelo-optico-neuropathy (SMON) and clioquinol: -A response to doubts about clioquinol causation theory-. Jpn J Med Sci Biol. 1975;28 (Suppl):35–55. [PubMed] [Google Scholar]
  44. Shigematsu I., Yanagawa H. Data on clioquinol and S.M.O.N. Lancet. 1978 Oct 28;2(8096):945–945. doi: 10.1016/s0140-6736(78)91664-1. [DOI] [PubMed] [Google Scholar]
  45. Shimada Y., Kosaka K. New cases of S.M.O.N. in Japan. Lancet. 1973 Feb 3;1(7797):268–268. doi: 10.1016/s0140-6736(73)90112-8. [DOI] [PubMed] [Google Scholar]
  46. Spillane J. D. S.M.O.N. Lancet. 1971 Dec 18;2(7738):1371–1372. doi: 10.1016/s0140-6736(71)92385-3. [DOI] [PubMed] [Google Scholar]
  47. Strandvik B., Zetterström R. Amaurosis after broxyquinoline. Lancet. 1968 Apr 27;1(7548):922–923. doi: 10.1016/s0140-6736(68)90280-8. [DOI] [PubMed] [Google Scholar]
  48. Tateishi J., Kuroda S., Saito A., Otsuki S. Experimental myelo-optic neuropathy induced by clioquinol. Acta Neuropathol. 1973;24(4):304–320. doi: 10.1007/BF00685586. [DOI] [PubMed] [Google Scholar]
  49. Tay C. H. S.M.O.N. in Singapore. Lancet. 1973 Jun 30;1(7818):1519–1519. doi: 10.1016/s0140-6736(73)91866-7. [DOI] [PubMed] [Google Scholar]
  50. Terry S. I. Transient dysaesthesiae and persistent leucocytosis after clioquinol therapy. Br Med J. 1971 Sep 25;3(5777):745–745. doi: 10.1136/bmj.3.5777.745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Tournilhac M., Flori B. Syndrome radiculocordonal postérieur et chloroiodoquinone. Nouv Presse Med. 1972 Dec 23;1(46):3132–3132. [PubMed] [Google Scholar]
  52. Tsubaki T., Honma Y., Hoshi M. Neurological syndrome associated with clioquinol. Lancet. 1971 Apr 3;1(7701):696–697. doi: 10.1016/s0140-6736(71)92699-7. [DOI] [PubMed] [Google Scholar]
  53. Vitale C., Feldman J. L., Hubault A., Weisbecker J., Bechetoille A., de Sèze S. Neuromyélite subaiguë avec névrite optique aprés chloroiodoquine. Un nouveau cas. Ann Med Interne (Paris) 1974 Dec;125(12):941–944. [PubMed] [Google Scholar]
  54. Worden A. N., Heywood R., Prentice D. E., Chesterman H., Skerrett K., Thomann P. E. Clioquinol toxicity in the dog. Toxicology. 1978 Mar;9(3):227–238. doi: 10.1016/0300-483x(78)90005-7. [DOI] [PubMed] [Google Scholar]
  55. de Crousaz G., Voumard C., de Werra P. A nephropathy in the genesis of S.M.O.N.? Lancet. 1973 Feb 17;1(7799):378–378. doi: 10.1016/s0140-6736(73)90175-x. [DOI] [PubMed] [Google Scholar]
  56. van Beeck J. A., Scholten J. B. Polyneuropathie na langdurig gebruik van clioquinol (Enterovioform. Ned Tijdschr Geneeskd. 1972 Sep 2;116(36):1621–1622. [PubMed] [Google Scholar]

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