THE CHANGES IN THE SPINAL CORD AND MEDULLA IN PERNICIOUS ANEMIA.

I DESIRE to express my appreciation of the honor conferred upon me by the officers of The Massachusetts Medical Society in inviting me to deliver the Shattuck Lecture. Many eminent men have preceded me in this honorable position, and it was with profound trepidation that I accepted the responsibility which precedent had established in giving a high tone to this lectureship. At the time I accepted the invitation to deliver the lecture, I was deeply interested in the subject which I chose for my paper. Pernicious anæmia has been the subject of considerable research work in a clinical way for several years, and as I have had the opportunity of observing the nervous phenomena and lesions of the nervous apparatus which may occur in this disease, I felt that it would be a proper subject for further investigation and report upon this occasion.

Lichtheim was given the credit for recognizing, for the first time, the spinal cord changes which may occur in pernicious anæmia. His report was based upon two cases, and was confined entirely to the changes of the cord in pernicious anæmia. Soon after this his student, Walter Minnich, reported one case in an inaugural dissertation.

The next important contribution was made by James J. Putnam, of Boston, who, in 1891, reported "A Group of Cases of Sclerosis of the Spinal Cord, Associated with Diffuse Collateral Degeneration Occurring in Enfeebled

Persons Past Middle Life, and Especially in Women; Studied with Particular Reference to Etiology." In this paper Putnam mentions Lichtheim's observations of cord changes in pernicious anæmia, and notes the similarity of the cord changes as compared with those observed in his patients. He also mentions the fact that Lichtheim ascribed the cord changes to some blood-circulating toxin. Putnam apparently accepted the toxic theory as the chief etiologic factor in his cases, but he emphasized the fact that the age, the sex, the neuropathic inheritance, poor physical development, nutritional disorders, diarrhoea, etc., were important. contributory causes. Putnam's paper did not receive the attention which it merited in Europe. The title was perhaps misleading, in that no mention was made of pernicious anemia.

Since 1891 many contributions upon the subject of the spinal cord changes of pernicious anæmia have been made. abroad and in this country. Nonne; Minnich; Bastianelli ; Burr; Russell, Batten, and Collier; Lloyd; Taylor; von Voss; von Noorden, and many others have reported cases and have described the clinical phenomena, the gross and histologic changes which have been found in conditions usually associated with pernicious anæmia, and also in conditions in which the blood condition was not like that of pernicious anæmia. Similar cord changes have also been noted and reported by some of the above-named authors, and by others in leukæmia, lathyrism, pellagra, diabetes mellitus, diphtheria, and associated with the degenerations incident to poisoning by phosphorus, lead and arsenic.

In 1902, Putnam made, with the collaboration of E. W. Taylor, a second report upon "Diffuse Degeneration of the Spinal Cord," in which a review and comparison of the views of many writers were noted. In this article Dr. Taylor made a most admirable report upon the pathologic anatomy of the nervous apparatus.

In view of these facts, I approach the subject with hesitancy, and proceed only with the hope that an additional report may be interesting, if it does not add anything new to the subject. My observations have been limited to the diffuse degenerations of the spinal cord of pernicious anæmia. The similarity of the cord lesions of pernicious anæmia and of the conditions enumerated by Putnam, by Russell, Batten and Collier and also by other reporters, is so striking that it must impress anyone who reviews the extensive literature of the subject. The similarity of the contributory etiologic factors of pernicious anæmia and of other conditions in which diffuse degeneration of the spinal cord occurs, as reported by Putnam especially, is notable. It is my object to present cases of pernicious anæmia, with the now recognized characteristic changes in the spinal cord, and to discuss somewhat the similarity of the cord changes in pernicious anæmia and in the other conditions above-mentioned.

It is possible that some of the earlier reported cases of diffuse degeneration of the spinal cord were not ascribed to an existing, but unrecognized, pernicious anæmia. It is just as likely, however, that some of the cases reported as pernicious anæmia, with cord changes, were not typical cases of that disease. This statement is based upon the fact that in some of the earlier cases reported the blood state is not noted sufficiently to enable one to recognize the case as one of a pernicious type of anæmia; and, furthermore, at the time when the first reports were made, the means of recognition and differentiation of the anæmias were not as clear as now. In earlier times pernicious anæmia was diagnosed upon the basis of a profound progressive anæmia, associated with a tendency to subcutaneous, submucous and retinal hemorrhages. When to these symptoms was added the post mortem finding of a characteristic, pale, anæmic fatty state of the organs, and especially of the heart, with an increase of iron in the liver, as was noted by

Quincke, and the presence of degenerated bone marrow, the diagnosis was certain. We now have a better knowlledge of the morphology of the blood. We are able to separate the primary from the secondary anæmias, and the blood of the pernicious type is characteristic and easily recognized. When we find a marked oligocythæmia, with the presence of many poikilocytes, microcytes, and macrocytes, with polychromatophilia, and a relatively high percentage of hæmoglobin, with a normal or a higher than normal color index, it affords a type of blood which is found in no other anæmic state. If to this we add the presence of nucleated red cells, and especially of megaloblasts, the fetal type of red cell and of a few myelocytes which together indicate degeneration of bone marrow, the diagnosis is reasonably certain without a postmortem examination.

CAUSE. Our knowledge of the cause of pernicious anæmia is not satisfactory. We recognize certain contributory factors and infer a condition of toxæmia which has not been proved. We know that the disease may occur in certain conditions; that these conditions are so frequently present in individuals who do not develop the disease, that we must look upon them as accidental.

Pregnancy, associated with constant vomiting and malnutrition, has been followed by pernicious anæmia. After repeated or severe hemorrhages, and in individuals who are poorly nourished, especially when the poor nutritional condition is associated with some error of physical development, a grave anæmia may follow. It is associated with, or follows most frequently, disease of the digestive apparatus. It has been known to follow syphilis and malaria, and in a few instances typhoid fever and la grippe seemed to be associated causes. In one of my cases the patient suffered from scarlet fever, was not well thereafter, and two years later developed the typical disease. The disease so infrequently follows the infections, like syphilis, malaria,

typhoid, la grippe, etc., that it is impossible to ascribe any specific relation to it.

In Berlin in ten years there were admitted to the hospital 148,000 patients, of whom 274 were diagnosed as pernicious anæmia, that is about .2 per cent. of all of the hospital cases. It is also stated that 22.4 per cent. of the above cases showed evidences of syphilis. This indicates that a small percentage of syphilitic patients develop pernicious anæmia. It is said, that individuals of a weak constitution and poor development are especially liable to the disease, yet the strong and full-blooded may develop it. The disease occurs more frequently in women than in men. Of the 274 cases mentioned, 172 were women, and 102 men. It may occur at any age, but it is more common in the fourth decade than at any other time in life. It has long been observed that the disease is frequently associated with some disturbance of the digestive tract. This consists in many instances of an atrophic condition of the walls of the stomach and of the intestine, which may become much thinned. The glandular elements of the mucous membrane have been found much atrophied. Achylia gastrica exists in many instances. In carcinoma of the stomach and in chronic glandular gastritis the same atrophy of the stomach wall may occur without pernicious anæmia. atrophic condition is also found in other portions of the body, and it is not at all unlikely that the condition of the stomach and the intestinal wall has only a contributory etiologic relation to the disease. Intestinal parasites have been found present in the disease, especially the bothriocephalus latus, and the ankylostoma duodenale. The disease, however, does not develop in all cases in which these parasites are present. That they have some relation to the disease is shown by the fact that some patients, who present characteristic blood findings, get well when the parasite is discharged by the patient. The condition of profound

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