CURATIVE TREATMENT OFLATHYRISM, A DISEASE OF THE NERVOUS SYSTEM

By H. JACOBY, m.d.

Chief Physician, Prince of Wales Hospital, Bhopal, Bhopal State

In a majority of diseases of the nervous sys- tem, neither a cause nor a cure is known, viz, in multiple sclerosis, syringomyelia, arnyo- tropic lateral sclerosis, spastic spinal sclerosis, etc.

In vast areas of India including Bhopal, a

disease prevails named '

lathyrism ', the symp- toms of which are identical with those of spas- tic spinal sclerosis. While for the latter disease we have no answer even to the question, whether exogene or endogene causes are respons- ible, we know in the case of lathyrism beyond any doubt that an exogene agent is the sole cause of it, namely the seed of Lathyrus sativus. In this part of India, we have come across no case of lathyrism which has been contracted without the consumption of Lathyrus as staple food for a period of at least a few months.

There is no cure for spastic spinal sclerosis (Beaumont, 1942; Price, 1941), nor for lathyr- ism. In a recent review on all that is known of lathyrism, Shourie (1945) writes : 'As far as at present known, the nervous lesions are per- manent and the disease incurable.' For lathyr- ism we have, however, found a drug which has definite curative properties.

Acetylcholine is a kind of hormone (Loewi) present in the human body and plays the most important role in the transmission of the nerve impulses. Under normal conditions, acetylcho- line is destroyed by cholinesterase only when it has served its purpose. We know, however, a pathological condition

(myasthenia gravis) in which it has been assumed that either an unbalance between pro- duction of acetylcholine and its destruction by cholinesterase exists (McGeorge, 1937) and causes disease, or in which the presence of

June-July, 1946] THE ELECTRON MICROSCOPE & ITS USE IN BIOLOGY : SEN 247

a poison-like toxic substance (for instance

curare) interferes with the normal transmission of impulses in the motor nerves (Fraser, 1938). For the treatment of lathyrism we went to

work with the hypothesis that in consequence

of the lathyrus intoxication the anatomical and functional lesions in the upper motor neurone

of the pyramidal tract go along with an un-

balance between production and destruction of

acetylcholine, thus interfering with the normal transmission of co-ordinated nervous impulses in the tract and causing the described symptoms. With a view to restituting this unbalance, we

resorted to a drug known to protect acetyl- choline against its destruction. Such a drug is the alkaloid physostigmine or eserine, occur-

ring in the Calabar bean, the seed of the

plant Physostigvici venenosum. Since, however, physostigmine has very undesirable toxic by- effects, we rather used its synthetic equivalent, by name prostigmin (Roche), which has exactly the same pharmacological properties as physos- tigmine. The same preparation has been used

^successfully in myasthenia gravis by Walker

A confirmation of the above concept that

prostigmin may facilitate the normal transmis- sion of nervous impulses in the pyramidal tract also, is given by the experiments of Schweitzer and Wright (1937), who have shown that

prostigmin depresses the knee-jerk-reflex through direct inhibitory action on the spinal cord. And

is known that the exaggerated deep reflexes, up to ankle- and patellar-clonus, are among the

characteristic features in lathyrism. Whatever the theoretical considerations on

the mechanism may be that led us _

to try

prostigmin for the treatment of lathyrism, the results achieved so far mark a conspicuous ad- vance in the treatment of this disease. We injected 1 c.cm. of prostigmin methyl-

sulfate containing 0.5 mg. into 14 patients intra- muscularly every day. We achieved a full success on 8 patients, i.e.

?71 per cent, each of whom received twelve

ejections. The success consists of abatement ?f the muscular rigidity and spasm in the lower

extremity as well as of all pains in the muscles ?f the calf and thigh, and occasional pains in the lumbar region. The gait of these patients,

^yhich previously had been spastic-paretic, became almost normal. . Three cases, i.e. 21.4 per cent, were greatly

unproved. Some resistance, however, in the

Muscles of the lower extremity on walking is

still noticeable and a slight ataxia exists by

standing on one foot with closed eyes. This

group of patients has also no pain any more. Two of them received twelve injections, one

received 24 injections. The third group of patients, three in number

(21.4 per cent), were practically not improved, although they admitted that their

_ pain was

relieved and that on walking they did no more scratch the ground

If we classify the cases into four groups according to the severity of the symptoms, we may say that those who are practically cured belong to groups I and II, who are greatly improved to group III and those who up to the present appear incurable to group IV.

It may, however, well be that with an im-

provement of our technique our results will still

improve and we shall give a full account of all our findings on a greater number of patients in due course. Eventually, we may express our

opinion that in view of the identity of clinical symptoms of lathyrism with spastic spinal sclerosis, the above treatment may also be applicable with success in the latter disease. AVe, however, see such cases very sparingly in

India, if at all.

Summary

Lathyrism is a nervous disease of the upper motor neurone in its clinical aspect identical with spastic spinal sclerosis. But whereas for the latter disease no cause and no cura-

tive treatment is known, we are well aware of the cause of lathyrism, i.e. consumption of the seed of Lathyrus sativus (Teora). With regard to treatment, we have found that prostigmin, the synthetic equivalent of physostigmine, has definite curative properties if given as injec- tion for a sufficient length of time. In this way, we treated 14 patients altogether, eight of whom, i.e. 57.1 per cent of the milder ones, were prac- tically cured. Three, i.e. 21.4 per cent, were

greatly improved and three, i.e. 21.4 per cent of the far advanced cases, were not improved so far.

REFERENCES

Beaumont, G. E. (1942). Medicine. J. and A. Churchill, Ltd., London.

Fraser, F. R. (193S) .. Brit. Med. J., i, 1349.

McGeorge, M. (1937) .. Lancet, i, 69.

Price, F. W. (1941) .. A Textbook of the Practice of Medicine. Oxford Uni- versity Press, London.

Schweitzer, A., and J. Physiol., 89, 165. Wright, S. (1937).

Shourie, K. L. (1945) .. Indian J. Med. Res., 33, 239. Walker, M. B. (1935) .. Proc. Roy. Soc. Med., 28,

759.

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