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LATHYRISM

BY BREVET-COLONEL R A M N A T H C H O P R A , C.I.E., Sc.D., M . D . , M.R.C.P., K.H.P., I.M.S.


PROFESSOR OF PHARMACOLOGY, SCHOOL OF TROPICAL MEDICINE AND M E D I C A L COLLEGE, CALCUTTA; SENIOR PHYSICIAN, CARMICHAEL HOSPITAL FOR TROPICAL DISEASES

1. D E F I N I T I O N 2. H I S T O R Y 3. A E T I O L O G Y

651 651 652 654 654 656 656 656

4. M O R B I D A N A T O M Y 5. C L I N I C A L P I C T U R E

6. C O U R S E A N D P R O G N O S I S 8. T R E A T M E N T -

7. D I A G N O S I S A N D D I F F E R E N T I A L D I A G N O S I S -

Reference may also be made to the following titles: DIETETIC DEFICIENCY DISEASES

VITAMINS

1.-DEFINITION
930.] Lathyrism is a disease caused by the ingestion of the seeds of a vetch of the genus Lathyrus, and is characterized by degenerative changes in the spinal cord.

2.-HISTORY
In India the disease has been known for centuries among the peasants. In the old Hindu literature, Bhavaprokasa, it is written that 'the triputa pulse' causes 'a man to become lame and crippled, and it irritates the nerves'. Hippocrates mentioned that the prolonged use of certain peas as food was liable to cause paralysis. In Don's System of Gardening the Lathyrus was cited as the cause of an epidemic paralysis on the Continent in the seventeenth century. So common was the affection in 1671 that George, Duke of Wurttemberg, issued an edict forbidding the use of Lathyrus. This edict was enforced by two others in 1705 and 1714 under his successor Leopold. In the eighteenth century the disease was observed in Italy, and large numbers of persons were affected in France, Algeria, and India. Sleeman reported an epidemic outbreak in the Saugor district 651

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AETIOLOGY

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1833-4. Irving contributed a series of valuable papers (1859-68) on outbreaks in the United Provinces. An extensive epidemic was recorded by Andrew Buchanan (1904) in the Central Provinces when about 7,600 persons were affected. Acton (1922) estimated that in North Rewa there were 60,000 victims or 6 per cent of the inhabitants. McCombie Young (1927) reported that in some areas as many as 13 per cent of the adult male population and 3 per cent of the adult female population were affected.

3.-AETIOLOGY
Geographic! incidence it Lathyn'sm occurs in those districts in which vetches, Lathyrus saiivus

Species of Lathyr us

and allied species, form the main article of diet. In India the disease is most prevalent and is commonly met with in the Central Provinces, North Bihar, and some districts in the United Provinces, although outbreaks are not unknown in Sind and Chota Nagpur. It also occurs to a lesser extent in France, Italy, Algeria, Abyssinia, and Persia. The three important species of Lathyrus which are regarded as causing the poisoning in man and animals are:

(i) Lathyrus sativus Linn., generally known in India as khesari dal, teora, or butiorah-ka-dal. The peas are of two sizes; the larger, known as lakh, is grown on dry wheat-land, and the smaller, iakhari, is cultivated on wet rice-fields. (ii) Lathyrus cicera Linn. This dwarf chick-pea is grown in France, Italy, and Algeria and is used as fodder for cattle. When wheat is dear, it is used instead of flour to make bread. (iii) Lathyrus clymenum Linn. The Spanish vetch is grown in Spain, North Africa, and the Levant. L. tuberosus and L: aphaca have also been regarded as possible causes. Lathyrus The Lathyrus peas yield a cheap food, the consumption of which is peas as food liable to produce the disease. The plants are hardy and grow well even during famine years. They therefore constitute the bulk, if not the whole, of the diet at such times, and it is then that lathyrism becomes prevalent. Apart from famines, large agricultural populations in some parts of India subsist to a great extent on Lathyrus peas, such as khesari, teora, and matra. These peas are used in several ways; they may be ground into flour and eaten raw; the flour may be made up in hand-made bread or chappaties. The vetch is also boiled in water with salt, and the thick pea-soup, known as dal, is eaten with rice or bread. During times of famine and drought it almost completely supersedes all other articles of food, including even rice and vegetables.
Susceptibility beings, are liable to lathyrism. Horses are peculiarly susceptible and of animals Responsible factor

Lathyrus is also used as food for domestic cattle which, like human

-fe

often have died after eating khesari dal. Elephants and monkeys are also known to be affected. There is little doubt that there is an intimate relation between the ingestion of L. sativus as food and the occurrence of lathyrism in

man. The exact factor responsible for its production is not yet understood. Stockman (1917) and Dilling (1920) extracted from the seeds of L. sativus minute quantities of an alkaloidal substance, with which they inoculated animals and produced symptoms resembling those of lathyrism. Acton and Chopra (1922) found in the seeds a toxin of the nature of a water-soluble amine, and produced symptoms resembling those of lathyrism in ducks and monkeys by injection of the soluble amine. Acton suggested that this toxic amine was produced in L. sativus during germination, and that this accounted for the high incidence of the disease during the rainy season of the year, July, August, and September. The results of animal experiments recorded by different observers have been conflicting. The discrepancy is mainly due to the fact that there is very commonly a contamination by the seeds of various weeds in the samples of Lathyrus. Howard, Simonsen, and Anderson elaborately studied the subject. They showed that samples of khesari, collected from many parts of India where lathyrism was prevalent, contained,, apart from Lathyrus sativus, various weeds which contaminated the true khesari. Feeding experiments on animals showed that the pure grain formed a harmless and nourishing food, and chemical investigation of numerous samples of botanically pure khesari failed to demonstrate the presence in the seed of bases of an alkaloidal nature. They showed that a vetch known as akta, Vicia saliva Linn. var. angustifolia, was present in all the samples of L. saliva. Chemical investigation of akta demonstrated the presence of bases having alkaioidal properties. Two such bases, vicine Vicine and and divicine, and a cyanogenetic glucoside, vicianin, were isolated. divicine The glucoside breaks up on hydrolysis into a sugar and the base divicine. Definite signs of poisoning with involvement of the central nervous system could be obtained with divicine in laboratory animals, such as guinea-pigs. Vicine is apparently non-toxic but by hydrolysis may become the toxic divicine; this can readily occur during gastric digestion. Although some of the symptoms in monkeys fed on diets containing akta are suggestive, there is still insufficient evidence to connect lathyrism in man with the ingestion of akta. McCombie Young pointed out that some other factor was responsible besides the mere presence of L. sativus in the diet, and he was inclined to believe that lathyrism Relation to might be to some extent a deficiency disease. Degenerative changes vitamins occur in the spinal cord of dogs fed on diets deficient in vitamin A. It is possible that the absence of vitamin A from the diet allows the neurotoxin in the peas to exert its harmful effects on the central nervous system. Stockman (1934) reported that a watery extract of Lalhyrus peas contained salts of phytic acid, which exerted a marked action on the brain and spinal cord. Moderate doses produced torpor and depression and larger doses clonic and tonic spasms. Feeding with large quantities of Lathyrus peas and the injection of the salts isolated from them caused degeneration of nerve-cells and nerve-fibres of the cerebrospinal and sympathetic systems. Stott, on the other hand, could

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CLINICAL PICTURE

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Racial incidence Age incidence Sex incidence

not produce toxic symptoms in horses by prolonged feeding of pure cultures of either L. salivas or Vicia saliva. It will thus be seen that there is divergence of opinion, and further investigation into the problem is necessary. Race, age, and sex are factors in its causation. The Hindus are particularly susceptible to the disease. The comparatively low incidence among the Mohammedans may be due to their mixed diet and also possibly to lower Mohammedan population in the affected areas. In the majority of the cases in Acton's series the age was between fifteen and thirty years, i.e. the most active period of life, but children are not exempt from the disease. It is curious to observe that women rarely suffer from lathyrism. It has been suggested that they eat less in order to save food for their husbands and children and are less exposed to inclemencies of the weather and hardship. Lathyrism usually affects poor people, the patients being generally peasants or casual labourers.

the legs, may have been noticed. Such cases, however, are few. Very often the disease follows over-exertion or exposure to cold or rain, the History victim finding the legs and loins weak and heavy. A typical history is that a patient has had a heavy day's ploughing and has taken shelter under a tree, and then finds that he is unable to walk and has to be carried home. Or he is at work in the field when he is seized with a rigor and fever; he goes home to bed for a few days, and on getting up

4.-MORBID ANATOMY
The patient rarely dies during the acute stages, and necropsies are almost impossible owing to religious prejudices. Probably the first histological study was carried out by Buzzard and Greenfield (1921), who reported a well marked degeneration in the crossed and direct pyramidal tracts and to a lesser extent in the column of Goll. Some marginal degeneration was also noticed. Filimonoff (1926) observed a sclerosis of the lateral region of the cord, not strictly confined to the pyramidal tract, throughout the lower cervical, dorsal, and upper lumbar cord. The small blood-vessels were sclerosed and obliterated in places. In horses well marked degenerative changes have been described in the cells of the grey matter of the cord, in the vagal and accessory nuclei of the medulla, in the lateral columns and motor nerve-roots of the spinal cord, and in the recurrent laryngeal nerves, with thickening of the walls of the arterioles and capillaries in the spinal cord. Fatty degeneration of the heart and of the laryngeal muscles supplied by the degenerated recurrent laryngeal nerve has also been found. No clinical evidence of lateral sclerosis in the cervical and dorsal region of the spinal cord is ordinarily seen, although Filimonoff found sclerosis in these regions.

L ^jsig? 1 S*'^!?1'

S& * * * &

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F I G . 159.Character of gait in different stages of lathyrism (From Indian Medical Gazette, 1922)

5.-CLINICAL PICTURE
The symptoms vary according to the quantity of khesari consumed daily and the period of time during which it was eaten. The onset is usually dramatically sudden. It occurs abruptly after the individual has been living on Lathyrus for two to five months. In a few cases the onset is insidious, and prodromal symptoms, such as fever, chills, backache, burning pains, cramps, and tingling or pins and needles in

Prodrome

he finds he cannot walk properly. The muscles become tremulous when Symptoms weight is put on them; there is dragging of the legs with inability to walk. Weakness and stiffness of the legs rapidly become more severe, reaching a maximum in a few days. After this there may be some symptomatic improvement, but the paresis persists indefinitely. Generally the sphincters are not affected, but occasionally there may be incontinence of urine and faeces. The sexual power is said to be enfeebled, but the mind, speech, and pupils escape. The affected muscles are in most cases not wasted, and sensation is generally normal. In a few cases the

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Signs Gait

[VOL. VII LATHYRISM arms have been affected in the same way as the legs. Convulsive movements of the extremities and muscular wasting have been observed. The physical signs are those of typical spastic paraplegia. The kneeand ankle-jerks are exaggerated, with ankle and patellar clonus and extensor plantar response. The characteristic gait depends on the degree of involvement of the spinal tracts; at first the attitude of the legs is one of extension with adduction, the patient walking on tiptoe; the body is raised high before the toes leave the ground, giving rise to up and down movement of the shoulders, and progression is effected by tilting the pelvis and circumducting the legs. The legs are crossed scissors-wise. The more feeble patients use one or two long sticks for support in walking. Later paraplegia in flexion develops, and in the final stages walking is impossible. Progression is made by crawling on the balls of the toes and on the hands, which are often supported on wooden sandals (see Fig. 159). In most cases the trunk and upper limbs are unaffected, and the chest and arm muscles are usually well developed owing to the extra work put upon them. The cerebrospinal fluid was found by Trabaud and others to contain an excess of protein with a normal cell count.

S.KEY930] TREATMENT 657 khesari dal must be discontinued, and exposure to chills and wet should be avoided. Massage and electrical treatment are sometimes helpful. The patient should be properly nourished. Mellanby (1934) has suggested the use of vitamin A. It is always desirable to see that the diet is generous and rich in available proteins and vitamins.

REFERENCES
Acton, H. W. (1922) Indian med. Gat., 57, 241. and Chopra, R. N. (1922) Indian med. Gaz., 57. 412. (1927) Trans. Far-East. Ass. trap. Med., 7th Congress, 3. 444. Buchanan, A. (1904) Report on Lathyrism in the Central Provinces in 18961902, Nagpur. Buchanan, W. J. (1899) J. trop. Med. (Hyg), 1, 261. Buzzard, E. F., and Greenfield, J. G. (1921) The Pathology of the Nervous System, London. Dilling, W. 1. (1920) J. Pharmacol.. 14. 359. Don, G. (1832-8) A General System of Gardening and Botany founded upon Miller's 'Gardeners Dictionary', London, 4 vols. Filimonoff, I. N. (1926) Z. gas. Neurol. Psychiat., 105, 76. Howard, A., Simonsen, J. L-, and Anderson, L. A. P. (1922) Indian J. med. Res., 10, 857. Irving, J. (1859) Indian Ann. med. Sci., 6, 424. (1861) ibid., 7, 127, 501. (1868) ibid., 12, 90. McCarrison, R. (1928) Indian J. mjd. Res., l j , 737. Mellanby, E. (1934) Nutrition and Disease. The Interaction of Clinical and Experimental Work, Edinburgh, p. 136. Sleeman, W. H. (1844) Rambles and Recollections of an Indian Official, London, 1, 134. Stockman, R. (1917) Etlinb. med. J., N.S. 19, 277, 297. (1929) J. Pharmacol, 37, 43. (1931) J. Hyg., Camb., 31, 550. (1934) ibid., 34, 145. Stott, H. (1930) Indian J. med. Res., 18, 51. Trabaud, J. (1929) Me'decine, 10, 910. Young, T. C. McC. (1927) Indian J. med. Res., 15, 453.

6.-COURSE AND PROGNOSIS


The disease runs a very chronic course. Degeneration limited to the motor tract is not a direct danger to life. The degeneration may be arrested, but there is not any possibility of cure in the sense of restoration to the previous condition of health. The degree of paralysis produced by the original attack remains permanent for the rest of life.

7 .-DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS


Diagnosis is made by the history of prevalence of other cases in the locality, inquiry into the diet, especially with regard to khesari dal, and the clinical manifestations of spastic paraplegia. Differential diagnosis must be made from other causes of spastic paraplegia, e.g. syphilitic myelitis, spinal caries and tumours, injury to the spine, disseminated sclerosis, subacute combined degeneration, amyotrophic lateral sclerosis, and syringomyelia.

8.-TREATMENT
Prophylaxis Prevention of the disease depends on the improvement of the economic condition of the poor agricultural population of India. Howard and his associates suggested that khesari dal should be planted in drills and the contaminating Vicia sativa removed by weeding. This should be done not only in places where lathyrism is rife but also in areas from which grain is sent to the famine-stricken areas. In view of the divergent views on the part played by Vicia in the spread of the disease successful measures cannot yet be devised.
Curative N o specific remedy for lathyrism is known. The consumption of
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LAURENCE-MOON-BIEDL SYNDROME
See BLINDNESS, Vol. II, p. 436; CEREBRO-RETINAL SYNDROMES OF THE HEREDO-DEGENERATIVE TYPE, Vol. Ill, p. 37; and PITUITARY GLAND DISEASES

E.M. VOL. VII

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