Abstract
Study design:
Case study.
Objectives:
Subacute myelo-optico-neuropathy (SMON) is a severe neuro-degenerative disorder caused by poisoning due to over-dose and prolonged oral administration of clioquinol; this disorder was more frequent during 1957–1970. It is characterized by axonal degeneration and gliosis in the cervical gracile fasciculus. Recently, copper-deficient myelo-neuropathies presenting similar symptoms (that is, painful dysesthesia/paresthesia in the lower limbs, ataxia, spastic paraplegia, autonomic disorders and visual impairment) were reported. Magnetic resonance imaging (MRI) of these patients detected T2-weighted hyperintensities in the cervical spinal cord. An unbalanced zinc–copper metabolism was suggested as one of the candidate pathogenesis of clioquinol toxicity because of its metal-chelating ability. The aim of this study was to present MRI findings of old SMON patients and to compare them with those of current copper-deficient myelo-neuropathies.
Setting:
Japan.
Methods:
We conducted and analyzed cervical and brain MRIs of seven old SMON patients who contracted the disorder during the 1960s. Serum iron, magnesium, copper, zinc and ceruloplasmin levels were also measured.
Results:
Cervical T2-weighted MRIs showed mild volume loss and faint hyperintensities in the dorsal columns, which might reflect residual gliosis. Brain fast fluid-attenuated inversion-recovery images and tractography were normal. Current levels of serum copper and zinc were within almost normal ranges.
Conclusion:
Although fainter, the abnormal T2 MRI signals we observed were similar to and occurred in the same locations as those reported in copper-deficient myelo-neuropathy patients. We suggest that these findings are useful to study the mechanism of clioquinol toxicity before using it to treat neurodegenerative diseases such as Alzheimer's disease.
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References
Tsubaki T, Honma Y, Hoshi M . Neurological syndrome associated with clioquinol. Lancet 1971; 1: 696–697.
Tateishi J, Kuroda S, Ikeda H, Otsuki S . Neurotoxity of iodoxyquinoline: a further study on beagle dogs. Jpn J Med Sci Biol 1975; 28 (Suppl): 187–195.
Sobue I . Clinical aspects of subacute myelo-optico-neuropathy (SMON). In: Vinken PJ BG, Cohen MM et al (eds). Handbook of clinical neurology, vol. 37 Elsevier: Amsterdam, 1979. pp 115–139.
Shiraki H In: Vinken PJ, Bruyn GW, Cohen MM, et al. (eds). Handbook of Clinical Neurology. Elsevier: Amsterdam, 1979. pp 141–198.
Nakae K, Yamamoto S, Igata A . Subacute myelo-optico-neuropathy (S.M.O.N.) in Japan. A community survey. Lancet 1971; 2: 510–512.
Konagaya M, Matsumoto A, Takase S, Mizutani T, Sobue G, Konishi T et al. Clinical analysis of longstanding subacute myelo-optico-neuropathy: sequelae of clioquinol at 32 years after its ban. J Neurol Sci 2004; 218: 85–90.
Shiraki H . Neuropathology of subacute myelo-optico-neuropathy, ‘SMON’. Jpn J Med Sci Biol 1971; 24: 217–243.
Konno H, Takase S . Neuropathology of longstanding subacute myelo-optico-neuropathy (SMON)]. Shinkei Naika 2005; 63: 162–169.
Spinazzi M, De Lazzari F, Tavolato B, Angelini C, Manara R, Armani M . Myelo-optico-neuropathy in copper deficiency occurring after partial gastrectomy. Do small bowel bacterial overgrowth syndrome and occult zinc ingestion tip the balance? J Neurol 2007; 254: 1012–1017.
Spain RI, Leist TP, De Sousa EA . When metals compete: a case of copper-deficiency myeloneuropathy and anemia. Nat Clin Pract Neurol 2009; 5: 106–111.
Kumar N, Knopman DS . SMON, clioquinol, and copper. Postgrad Med J 2005; 81: 227.
Schaumburg H, Herskovitz S . Copper deficiency myeloneuropathy: a clue to clioquinol-induced subacute myelo-optic neuropathy? Neurology 2008; 71: 622–623.
Nations SP, Boyer PJ, Love LA, Burritt MF, Butz JA, Wolfe GI et al. Denture cream: an unusual source of excess zinc, leading to hypocupremia and neurologic disease. Neurology 2008; 71: 639–643.
Kumar N, Gross Jr JB, Ahlskog JE . Myelopathy due to copper deficiency. Neurology 2003; 61: 273–274.
Hedera P, Fink JK, Bockenstedt PL, Brewer GJ . Myelopolyneuropathy and pancytopenia due to copper deficiency and high zinc levels of unknown origin: further support for existence of a new zinc overload syndrome. Arch Neurol 2003; 60: 1303–1306.
Hedera P, Peltier A, Fink JK, Wilcock S, London Z, Brewer GJ . Myelopolyneuropathy and pancytopenia due to copper deficiency and high zinc levels of unknown origin. II. The denture cream is a primary source of excessive zinc. Neurotoxicology 2009; 30: 996–999.
Schleper B, Stuerenburg HJ . Copper deficiency-associated myelopathy in a 46-year-old woman. J Neurol 2001; 248: 705–706.
Kumar N, Ahlskog JE, Klein CJ, Port JD . Imaging features of copper deficiency myelopathy: a study of 25 cases. Neuroradiology 2006; 48: 78–83.
Gouras GK, Beal MF . Metal chelator decreases Alzheimer beta-amyloid plaques. Neuron 2001; 30: 641–642.
Kaur D, Yantiri F, Rajagopalan S, Kumar J, Mo JQ, Boonplueang R et al. Genetic or pharmacological iron chelation prevents MPTP-induced neurotoxicity in vivo: a novel therapy for Parkinson's disease. Neuron 2003; 37: 899–909.
Acknowledgements
We thank the patients for their contribution to this study, Jason Cole for medical English editing, and Tomoko Nakayama and Akiko Hamada for their helpful secretarial assistance. This study was financially supported by the Ministry of Health, Labor, and Welfare of Japan.
 Authors' contributions: EK was the primary neurologist, conceived the original study, organized and analyzed the data, prepared the draft of the paper, and supervised the entire study. TH contributed to the original idea and helped write and edit the final draft of the paper. SY, YU and YM were consulting neurologists, evaluated MRI data, and assisted with paper editing. TH was the chief consultant regarding neuro-radiological evaluations. MU analyzed the data and helped write and edit the paper.
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Kimura, E., Hirano, T., Yamashita, S. et al. Cervical MRI of subacute myelo-optico-neuropathy. Spinal Cord 49, 182–185 (2011). https://doi.org/10.1038/sc.2010.68
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DOI: https://doi.org/10.1038/sc.2010.68
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