Subacute Myelo-optico-neuropathy Research Articles

Subacute myelo-optico neuropathy (SMON) in Hokkaido, an epidemiological study. I (author's transl)

A statistical study was conducted on SMON (subacute myelo-optico neuropathy) in Hokkaido, taking the theory of clioquinol etiology into consideration.Results obtained are following:1. In Hokkaido, SMON began to occur sporadically about 1958, reached epidemic proportions from 1962 to 1966 and then abruptly declined. Up to the end of September, 1972, a total of 433 cases had been confirmed or strongly suspected to be SMON.2. The incidence was highest in the fifth decade of both sexes. The over-all sex ratio was 1:2.1, (i.e. twice as high in females), and progressed with age to 1:5.3 in the eighth decade.3. There were marked regional differences in the incidence of SMON, but these did not reflect population size. However, the incidence was closely related to the presence of medical institutions in which clioquinol was administered in excess to patients with gastrointestinal disorders.4. It was statistically confirmed that the daily dose of clioquinol, the duration of administration of the drug, and the number of persons who received it showed a high correlation with the incidence of SMON. It was noted, however, that the daily dose related to the incidence differed with the medical institution.5. In some areas, the decrease in the occurence of new SMON cases slarted before September, 1970, when the use of clioquinol was officially discontinued. The earlier disappearance of SMON appears to have been due to the reduction in the daily dose of cliquinol prescribed in the medical institutions in these areas.

HISTOCHEMICAL DEMONSTRATION OF CHINOFORM

Chinoform (7-iodo-5-chloro-8-hydroxyquinoline) which is a derivative of oxin (8-hydroxyquinoline) can chelate with some metals as well as oxin and other derivatives. Applying this principle, the techniques of histochemical demonstration for chinoform, which is probably the causal agent of subacute myelo-optico-neuropathy (SMON), were devised.Copper, iron and silver were used as substances to be chelated with chinoform and they were demonstrated histochemically. In using these techniques, it was necessary to perform these chemical reactions in Tween 80 solution.The possibilities of these techniques were examined using various kinds of materials.Insoluble chinoform hydrolyzed from chinoform glucuronide as a substrate by β-glucuronidase activity deposited ill situ positively and was demonstrated histochemically. In addition, the devised techniques were tested and comparisons were made with the autoradiographic findings in the tissue sections of rabbits to which 131I-chinoform was administered.

SUBACUTE MYELO-OPTICO-NEUROPATHY (S.M.O.N.) IN JAPAN: A Community Survey

An epidemiological survey of subacute myelo-optico-neuropathy (S.M.O.N.) was made in Toda City (population 65,000) and Warabi City (population 76,000), Japan. In Toda City, after an outbreak in 1964, the occurrence was sporadic. In Warabi City the incidence was lower and less variable. The highest incidence was in middle-aged females; no cases were found in children. Out of 47 cases examined, 36 had been treated at 2 particular medical institutions (A and B) at the time of onset of neurological symptoms, although there were 52 medical institutions in the areas. The remaining 11 cases had been treated in other medical institutions inside and outside the areas. Review of the National Health Insurance returns from 30 medical institutions in Warabi City revealed that the highest dosage of clioquinol was used in medical institution B. No case of S.M.O.N was observed in 20 medical institutions which did not use clioquinol. In medical institution A, 17 out of 21 patients with confirmed S.M.O.N. (81%) had been given clioquinol before the onset of neurological symptoms. A comparative study showed that the dosage of clioquinol to S.M.O.N. patients had been heavier than to other patients with similar enteric symptoms.

Electron microscopical study of a nerve biopsy from a case in the chronic state of "subacute myelo-optico-neuropathy".

N. suralis, taken from a patient in the chronic state of “Subacute Myelo-Optico-Neuropathy (SMON)” was examined by electron microscopy. The nerve showed a depletion of myelinated nerve fibres. Vacuoles or degenerated mitochondria were observed in the axis cylinders of myelinated and unmyelinated nerve fibres. Schwann cells were increased in number and many of them were atrophic. Onion-bulb formations were seen diffusely; regeneration of myelinated nerve fibres was sparse.

ヒト末梢血由来リンパ芽球様株細胞に関する研究

Nine new lymphoblastoid cell lines have been established from peripheral blood leukocytes of patients with infectious mononucleosis, subacute myelo-optico-neuropathy (SMON), acute myelogenous leukemia and chronic lymphatic leukemia.All the cell lines grow in suspension and mostly consist of lymphoblastoid cells regardless of the cell source and clinical status of the donors. A few percentage of Epstein-Barr virus (EBV) antigen-positive cells were detected by the immunofluorescence method in all the cell lines. These cell lines have maintained karyotypes of predominantly normal diploid modes. It is suggested that the origin of these cell lines may be certain lymphocytes in peripheral leukocytes.From the present study, a following hypothesis may be offered on the establishment of the lymphoblastoid cell lines. It is conceivable that EBV which is harbored in vivo in lymphocytes might be activated and replicate in the early stage of leukocyte culture. The virus would, thereafter, exert an antigenic stimulation on some of the lymphocytes and consequently they would undergo blastoid transformation, yielding self-sustaining cell lines.

肝,腎障害ラットにおける放射性キノホルムの代謝とミクロラジオオートグラフイー

Recently, chinoform has come to attract the attention as one of the etiologic factors of the disease, subacute myelo-optico neuropathy commonly known as SMON in Japan. For the purpose to study the metabolism of chinoform in vivo, a series of experiments were conducted with labeled chinoform (131I-chinoform) with rats of Wistar strain. As a step to increase the toxicity of chinoform, carbon tetrachloride was administered to the rats to induce liver disturbances as to increase the chinoform retention in vivo, and as another step rabbit-antirat kidney serum was injected to the animals so as to elicit allergic nephritis, and then 131I-chinoform was intravenously injected each of these two groups of animals. The next procedure was to analyze the in vivo distribution of 131I-chinoform. The results of the study are briefly summarized as follows.In the case administered with carbon tetrachloride practically all the central nervous system and the sciatic nerve revealed a higher radioactivity of free chinoform, and also the percentage of free chinoform to the total chinoform was greater as revealed by the radioactivity of the chloroform-soluble fraction. By microautoradiography, labeled chinoform was detected in Purkinje cells and glial cells in the molecular layer of the cerebellum, glial cells of the thalamus as well as the brain stem, and in the posterior root ganglia, anterior horn cells and meninges of the spinal cord. In the liver it was observed in Kupffer stellate cells and cholangioli and slightly in hepatic cells. As for the kidney, the labeled chinoform was markedly incorporated in the proximal convoluted tubuli and slightly in the glomeruli. Next, in the rats with experimental nephritis, the decreasing rate of radioactivity in the blood was relatively low as compared with that of the control group. In the kidneys the radioactivity was high in the total fraction, chloroform-soluble fraction and chloroform-insoluble fraction as compared with respective values in the controls, showing 30 to 50-fold values.

腹部症状を伴う非特異性脳脊髄炎症(SMON)の疫学

腹部症状を伴う非特異性脳脊髄炎症(SMON)の疫学

Epidemiological Studies on Subacute Myelo-optico Neuropathy (SMON) in the town of Yubara, Japan (Report 2)

SMON (subacute myelo-optico neuropathy) which broke out in Yubara, Japan was studied by examination of public records kept by the Town authority, responses to questionnaires by all the families in the town, interviews with patients and home visits in order to investigate environmental conditions.Some of the results have been published previously in this journal. This will be the second publication in this series, chiefly based on the second field survey performed at the beginning of this year. The results are as follows:1) In Yubara township, located in the northern part of Okayama Prefecture, an outbreak of SMON was reported at the beginning of 1967. The incidence increased gradually, reaching its peak in September 1968, and then diminished slowly during 1969. There were no cases of SMON reported in 1970. (until March) Total number of the cases reported were 81. The yearly incidence rate is 486per 100, 000 population during the 3 year period.2) Sex ratio was 3.3 females to 1 male patient. As for age distribution, males revealed highest rate in their thirties, while females showed high rates in those aged from twenties to sixties. The phenomenon called “die Prazession der Durchseuchung, ” was not observed.3) Geographical distribution spread from the center to the peripheral parts of the town each year.4) Although cluster of cases were found within families and their social contacts, no one could be identified as the source of spread.5) Caterers, sales men and women, local public health employees and hospital employees were noted to have high attack rates in the early stages of the epidemic, but the disease later spread among farmer population as well.6) Appendicitis, appendectomy, chronic diseases and constitutional disorders were more frequently observed in the medical histories of the patients than in the control group.7) The results of water examination by the local health center, showed occasional coli-contamination of the local water supply during the summer months.

Epidemiological Studies on Subacute myelo-optico-neuropathy (SMON) at Yubara Town (Report 1)

In a restricted area of the northern part of Okayama Prefecture, Yubara Town, an outbreak of SMON (subacute myelo-optico-neuropathy) was observed from the beginning of 1967. An epidemiological investigation has been made on this outbreak and the results are as follows:(1) Concentration of cases occurred in the summer of 1968, though cases have been reported sporadically in the area from the beginning of 1967. The incidence ratio against the population was 659/100, 000 during 22 months.(2) The incidence was the highest in summer and the ratio in females was 3 times higher than in males. Concerning age group, males showed a peak in the thirties, whereas in females many cases were evident between the twenties and sixties.(3) Relatively enclosed districts are apt to expand over a period of time. Cases which occurred in neighboring families as well as those within the same families tend to give the impression that the disease coule be infectious.(4) Among the cases, a close contact relation was observed.(5) Physical exhaustion before the onset of the disease was observed to be 43.2% among the total cases.(6) In occupational analysis, a higher rate was revealed among workers who had close human relations such as hospital workers and public service personnel.(7) The tendency to other diseases of the nervous system as well as those of the digestive organs was checked by inspecting receipts of the National Health Insurance from the beginning of 1965. Nothing related to SMON was recognized before the outbreak.(8) Diseases of the intestinal tract and tonsillitis were observed in higher rates in the history of the patients.(9) The investigation of environmental conditions has revealed the fact that there is a higher rate of incidence in families who do not use service water compared to those who do.