The treatment of subacute combined degeneration / by Edward Mellanby.

  • Mellanby, Edward, Sir, 1884-1955
Date:
[1933?]
Catalogue details

Licence: In copyright

Credit: The treatment of subacute combined degeneration / by Edward Mellanby. Source: Wellcome Collection.

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    My attention was first attracted to this subject about ten years ago when I noticed that some of my experimental dogs in which I was studying the cause of rickets, developed severe inco-ordination of movement and other symptoms of nervous disorder. After having decided that this condition was independent of rickets, I examined their nervous systems and found extensive myelin degeneration in certain parts of the spinal cord [1]. It became evident in course of time that there were two properties of the diet which produced these degenerative changes ; (l) it contained much cereal, and (2) it was deficient in fat-soluble vitamins. Cereal content of diet.-—Whereas the nervous changes were evident when white flour formed the cereal factor of the food, they were increased when wheat germ or embryo was added. Since the behaviour of the dogs and the nerve degeneration in the cord reminded me of the clinical condition known as convulsive ergotism in man, it seemed possible that the wheat embryo which increased the morbid changes was ergotized, i.e. invaded by the mycelium, Claviceps purpurea. Microscopic examination did not support this possibility, but my attention having been drawn to ergotism, I proceeded to add ergot of rye to the diets and found that this increased the nerve degeneration. Rye germ not infected by the ergot mycelium also increased the cord changes. In fact, it became clear that all cereals tested (with one exception) under these particular experimental conditions, allowed demyelination of conducting nerves in the cord to develop, and that cereal embryo and especially ergotized rye germ made the condition worse. I assumed that cereal and especially cereal embryo and ergot contained a neurotoxin. The exception among cereals was yellow maize for a reason which will be obvious later. When yellow maize was eaten no degeneration was produced even when additional ergot was eaten. White maize, on the other hand, allowed these changes to develop [2]. Vitamin A and carotene as the protective factor.—It has been mentioned above that the cord changes only occurred when the diets were deficient in fat-soluble vitamins, and it became necessary to see which vitamin was capable of exerting this protective influence. At first this was a matter of some difficulty, as the earlier work was done before a clear differentiation between vitamins A and D had been made. With the preparation of pure vitamin D it was possible to add this singly to the diets, and it was then evident that this particular substance was not the protective factor. It was indeed found that ergot itself contained vitamin D, and it was unlikely that a substance which made the degenerative changes worse should contain a protective vitamin in any quantity. Thus while ergot prevented rickets in these young animals, it made the spinal cord degeneration more severe. When attention was now turned to vitamin A, it soon became evident that this was the essential protective factor, for any source of this vitamin prevented the nerve degeneration. Thus butter, egg-yolk, mammalian liver or liver oil had a protective action. Green vegetables and carrots also had the same protective influence, and this led to the idea that carotene, in this as in other biological properties, acted like vitamin A. This was found to be the case, for the addition of 2 to 3 mgm. of carotene to the diet daily prevented the myelin degeneration even when ergot was present in the diet. It is impossible here to discuss these experimental results or their significance in any detail, but reference may be made to a few more outstanding points. (a) Of the two dietetic factors which form the basis of these results—a neurotoxic influence associated with cereals, and a protective fat-soluble vitamin—the latter is the more important. In my experience the neurotoxic element is ineffective in the presence of the protective factor. On the other hand, even in the absence of cereal, I have produced similar results in young dogs by feeding them on synthetic diets of pure protein, fat and carbohydrate, such as are given in rat experiments, when the vitamin A and carotene have been deficient. Zimmermann 13] has produced similar results in rats by giving them cereal-free vitamin-A-deficient diets.