The clinical manifestations, roentgenologic studies, and histopathologic findings of the central nervous system of rats with induced lathyrism were described.
The question of whether the experimental lathyrism is due to a primary central nervous system involvement or is entirely secondary to bony abnormality is not conclusively answered by this study. However, the evidence of diffuse widespread vacuolization which is more marked in the
cord, medulla, and cerebellum than in the hemisphere, strongly suggests the former etiology.</p

Lee, HUN Jae

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Observation of experimental lathyrism in the rat

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Acta Medica OkayamaVolume 13, Issue 3 1959 Article 6OCTOBER 1959Observation of experimental lathyrism in theratHUN Jae Lee∗∗Soo Do Medical College Seoul,Copyright c©1999 OKAYAMA UNIVERSITY MEDICAL SCHOOL. All rights reserved.Observation of experimental lathyrism in therat∗HUN Jae LeeAbstractThe clinical manifestations, roentgenologic studies, and histopathologic findings of the cen-tral nervous system of rats with induced lathyrism were described. The question of whether theexperimental lathyrism is due to a primary central nervous system involvement or is entirely sec-ondary to bony abnormality is not conclusively answered by this study. However, the evidence ofdiffuse widespread vacuolization which is more marked in the cord, medulla, and cerebellum thanin the hemisphere, strongly suggests the former etiology.∗Copyright c©OKAYAMA UNIVERSITY MEDICAL SCHOOLActa Med. Okayama 13, 220-226 (1959)OBSERVATION OF EXPERIMENTAL LATHYRISMIN THE RATHUN JAE LEE*Soo Do Medical College Seoul, Republic of KoreaReceived for publication, March 5, 1959Human lathyrism resulting from prolonged ingestion of the sweet pea(Lathyrus odoratus) has long been recognized in the Mediterranean areaand in India1.2. There have been many reports of observation on experi-mental lathyrism in rats following the initial works of GEIGER et al3• re-ported in 1932.Symtpoms so far described consist of ataxia, tremor, kyphos-coliosis, spastic paraplegia, degenerative arthritis, exostosis, dissect-ing aortic aneurysms, and incontinence. The toxic factors of the sweetpea have been indentified as p-(r-l-glutamyl) aminoproprionitrile and 11-aminonitrile4.5• Neurologic manifestations have been consistently ob-served, but the mechanism of their production remains still obscure.The purpose of this study was to observe the microscopic pathologicchanges of the central nervous system in the condition and to attemptto reveal the correlation of such changes with the clinical findings.MA.TERIAL, METHOD AND RESULTTwenty albino rats of the Wistar strain weighing an average 40 gmswere used. Sex distribution rate was l: 1. Subjects were divided into twoequal groups (10 in each), one for the control and one for the experiment.Animals selected were young,aged 3 weeks,as it was anticipated that changesmight be more readily produced in the developing central nervous system.Control animals were maintained on the usual laboratory diet (Rocklandcomplete rat diet). The experimental group was fed with the diet consistedof 70 % sweet pea and 30 % Rockland diet. Animals were weighed andevaluated carefully at weekly intervals during the 42-day period of study.Throughout the entire period of 42 days, all control animals exhibitedsleady growth and weight gain without significant symptoms. Experi-mental animals, without exception, gained weight at about half the rateof the control animals and developed definite evidence of lathyrism after* Present Adress: Department of Surgery, Section of Neurosurgery, Universityof Michigan Medical School, Ann Arbor, Michigan, U. S. A.2201Lee: Observation of experimental lathyrism in the ratProduced by The Berkeley Electronic Press, 1959Observation of Experimental Lathyrism in the Rat 2213 weeks. Three rats died during the period of study after developingsevere symptoms. Two of these, dying at 30 and 35 days, were eaten bythe other rats, so that pathologic findings could not be obtained. A thirdanimals, dying on the 25 day, was found to have pericardial hemorrhagesuggesting dissecting aortic aneurysm.Remaining animals all developed kyphosis, tremor, ataxia, spastic pa-raplegia and decreased reaction to painful stimuli below the mid dorsalarea (Fig. 1). All were incontinent and appeared generally ill. Further-more animal ~ 1 developed a large ventral hernia, and ~ 3, ~ 5, and :;; 6also developed smaller inguinal hernias.Fig. 1. Experimental rats receiving the 70% sweet pea diet developed,without exception, ataxia, tremor, kyphoscoliosis, spastic palaplegia, in-continence and decreased reactions to painful stimuli within 3 weeks.All animals were sacrificed on the 42nd day. The accompanying illu-strations demonstrate kyphosis of the dorsal spines and hernias (Fig. 2).One animal with severe lathyrism was returned to the usuallabora-tory diet on the 42nd day and was observed for another 10 days. Therewas surprising improvement of the spastic weakness and of reactions topainful stimuli, and diminution of tremor during this period.The brain and cord were removed from the sacrifice animals and fixedin 10% formalin. Six experimental subjects showed the marked angulationof the cord in the lower dorsal region, but compression of the cord could2Acta Medica Okayama, Vol. 13 [1959], Iss. 3, Art. 6http://escholarship.lib.okayama-u.ac.jp/amo/vol13/iss3/6222 HUN JAE LEEFig. 2. Roentogenologic studies of the sacrifice rats on the 42nd day of theexperiment. A is the roentogenogram a of a control animal. B, C and Dare roe-ntogenograms of the experimental group and these demonstrate marked kyphosco-liosis of dorsal spines associated with ventral or inguinal hernia.3Lee: Observation of experimental lathyrism in the ratProduced by The Berkeley Electronic Press, 1959Observation of Experimental Lathyrism in the Rat 223Fig. 3. Histopathological findings of the central nervous system of rats withinduced lathyrism. Diffuse widespread vacuolization were most marked in thecord and diminished in ascending sections. A, B, C, D, E sections were stained withthe Weil's myelin stain and A', B', C', D', E' with the Thionin technique for cellularstructures. A, A' sections were made from the cord below the angclation, B, B' atthe site of angulation and C, C' from above the angulation. D, D' sections weremade from the cerebellum and E, E' from the hemisphere.4Acta Medica Okayama, Vol. 13 [1959], Iss. 3, Art. 6http://escholarship.lib.okayama-u.ac.jp/amo/vol13/iss3/6224 HUN JAE LEEnot be confirmed on gross examination. Sections were made below, at,and above the angulation of the cord. Additional sections were made toinclude medulla, cerebellum, midbrain and hemispheres. Sections werestained with VotTeil's myelin stain technique and with the Thionin tech-nique for cellular structures.Examination of these sections revealed large pericellular clear areas(Vacuolization). Similar spaces were seen separating fibers in the longtracts. These were distributed throughout, but were more marked in thecord, medulla and cerebellum than in the hemispheres. Furthermore,these were most marked in the cord and diminished in ascending sections(Fig. 3). These were more markedly demonstrated in the Weil-stainedsections. There was no demyelinization or evidence of neuronal structuralchange noticed to indicate structural damage due to kyphosis of the cordin this study. Vacuolization did not appear to involve cortico-spinal orother tracts in a differential manner. These pathological findings werenot found in the control animals.DISCUSSIONDegeneration of the lateral columns in human lathyrism was presentin two reported human cases in literature 6. The clinical picture of lathyrismin rats and human beings is not identical. Nevertheless, there are manypoints of similarity between the roentgenologic characteristics of lathy-rism scoliosis in rats and idiopathic scoliosis in human beings.Human idiopathic scoliosis is believed to be related to defective pro-tein metabolism. However, lathyrism scoliosis was not prevented, northe onset of symptoms delayed, in rats receiving 10 % casein with a sweetpea diet. This would suggest that altered protein metabolism is not theprimary change in rat lathyrism 7.GEIGER, LEWIS, et. al8 9, as regards the cause of rat lathyrism, des-cribed the spastic paralysis observed in their experimental animals andsuggested that it might be due to cord compression at the site of the ky-phosis rather than to a primary neurologic lesion. On the contrary, VI-VANCO and GIMENEZ10 thought that the origin was neurotoxic according totheir experiment in which extensive laminectomy performed prior to in-ducing lathyrism in rats failed to prevent paraplegia, but did effectrecovery on returning the affected rats to a normal diet. A similar factwas observed in this experiment, as noted before.It is obvious that the clinical picture of rat lathyrism shows not onlyspastic paraplegia but specific symptoms of the central nervous system5Lee: Observation of experimental lathyrism in the ratProduced by The Berkeley Electronic Press, 1959Observation of Experimental Lathyrism in the Rat 225involvement such as ataxia, tremor, and restlessness.PONESTI, et. aPl tried to demonstrate the histopathological changes ofthe central nervous system related to the clinical toxic symptoms in lathyri-nized rats, but no definite microscopic changes were obtained except somelocal destruction of the cord at the site of the kyphosis in the rats withparaplegia.Whereas, as described above, diffuse, widespread pericellular vacu-olization in the cord, medulla, cerebellum, and less in the hemisphere,was observed in this study. These microscopic findings could be con-sidered as the toxic changes of the central nervous system related to theclinical manifestation, namely the spastic paralysis of rat lathyrism.Furthermore, the recovery from the clinical symtoms by returning theaffected rats to a normal diet is more easily explained as a diffuse rever-sible involvement of the central nervous system rather than as a simplemechanical destruction of the cord secondary to kyphosis.CONCLUSIONThe clinical manifestations, roentgenologic studies, and histopatho-logic findings of the central nervous system of rats with induced lathyrismwere described.The question of whether the experimental lathyrism is due to a pri-mary central nervous system involvement or is entirely secondary to bonyabnormality is not conclusively answered by this study. However, theevidence of diffuse widespread vacuolization which is more marked in thecord, medulla, and cerebellum than in the hemisphere, strongly suggeststhe former etiology.Lastly, I wish to express my grateful thanks to Drs. R. C. SCHNEIDER and E. C.CROSBY of the University of Michigan and to Dr. D. JINNAI of the Okayama Universityfor their advice and encouragement in the publication of this article.REFERENCES1. ANDERson, L. A. Po, HOWARD. A., and SIMONSEN, J. L.: Studies on lathyrism 1. Ind.]. med. Res. 12, 613-643, 1925.2. ACTION, H. W. and CHOPRA, R. W.: The causation of lathyrism in man. Trans. Thecongress Far East Assoc. Trop. med. 3, 444-449, 1927.3. GEIGER, B.]., STEENBOCK. Ho, and PARSONS, H. T.: Lathyrism in rats. ]. Nutri-tion. 6, 42i -442, 1933.4. DASLER, W.: Production of experimental lathyrism in the rat by two differentbeta-substituted ethylamines (21535). Froc. Soc. Ex p. Bioi. med. 88, 196, 1955.5. SCHILLING, E. Do, and STRONG, F. M.: Isolation, Structure and Synthesis of a la-6Acta Medica Okayama, Vol. 13 [1959], Iss. 3, Art. 6http://escholarship.lib.okayama-u.ac.jp/amo/vol13/iss3/6226 HUN JAE LEEthyrus factor from L.Odoratus. ]. Amer. Chem. Soc. 76, 2848, 1954.6. STOCKMAN, R.: J. Pharmacol. and Exper. 1952.7. IGNACIO, V. P., and WIELIAM, A. B.: A.]. of Path. 28 (6), 1059-1078, 1952.8. GEIGER, B. J., STEENBOCK., H., and PARSONS, H. T.: ]. Nutrition 6, 427-442, 1933.9. LEWIS, H. B., and SCHULERT, A. R.: Experimental lathydsm in the white rat.Proc. Soc, Exper. BioI. and med. 71, 440-441, 1949.10. VICANCO, F., and GIMENEZ, D. C.: Nueuos estudios sobre 10s eferos de laslegumbres (leguminismos). Rev. Clin. espan. 14, 157-162, 1951.11. PONSETI, 1. V., and BAIRD, W. A.: Scoliosis and dissecting aneurysm of the aortain rats fed with L. Odoratus seeds. A.]. Path. 28, 1059-1077, 1052.7Lee: Observation of experimental lathyrism in the ratProduced by The Berkeley Electronic Press, 1959

Experimental lathydsm in the white rat.

Lathyrism in rats.

Nueuos estudios sobre 10s eferos de las legumbres (leguminismos).

Production of experimental lathyrism in the rat by two different beta-substituted ethylamines (21535).

Scoliosis and dissecting aneurysm of the aorta in rats fed with L. Odoratus seeds.

Structure and Synthesis of a la6

The causation of lathyrism in man.

Observation of experimental lathyrism in the rat

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