anæmia, with deformed red cells, the presence of fetal red cells in the circulating blood, the presence of an abnormal amount of iron in the liver, together with degenerative changes in the muscles and in the marrow of bone, is a reasonable hypothesis for the assumption of the presence of a circulating poison-a hæmolytic toxin as the fundamental cause of the disease. The source of the poison has been the subject of many theories.

Schauman and Tallquist have brought forward the theory that in cases of pernicious anæmia due to the bothriocephalus latus, the parasite was the source of a toxin because the worm itself was either sick or dead in the host. In this condition the worm was the source of the toxin which produced the anæmia, and explained to these reporters the reason for the non-development of pernicious anæmia in most cases of individuals affected with the bothriocephalus latus. They made the following experiment: The extract or bruised links of the bothriocephalus latus was fed to dogs. In one dog, after two weeks, marked anæmia occurred, the red cells falling from 7,200,000 to 3,400,000.

The view has been advanced that the toxin is of bacterial origin, but no definite observations have been made which would establish this, with the exception of the research work done by Professor Adami and his pupils. In his studies upon hypertrophic cirrhosis of the liver and on hæmochromatosis in pernicious anæmia, Adami advances the opinion that many of the sclerotic processes of the body are due to acute and chronic infection through the presence in the tissues of bacteria or bacterial poisons, which may be derived from the intestines. The organism is successful in overcoming the general infection, but the tissue cells become exhausted through the specific infection, with resulting degeneration and connective tissue hyperplasia. He described diplococcoid forms of bacteria in the stomach and intestinal walls, and in the liver cells, which he believed to

be altered colon bacilli. The suggestion of Adami is very pertinent, especially if one believes that pernicious anæmia is due to a toxin.

More recently Hunter, who had confirmed the observations of Quincke and others as to the hæmolytic effect of a possible toxin, suggested the origin of the poison in the intestinal canal from the altered anatomic condition of the stomach and bowel. Still later, Hunter has suggested the idea that the toxin and the condition of the gastro-intestinal canal have their source in a foul condition of the mouth of the patient, who suffers from pernicious anæmia, and he notes the condition of carious teeth, gingivitis, etc., in many of his patients. It is not improbable that from the evidence we have, pernicious anæmia is due to some hæmolytic toxin, but whether of bacterial or autogenetic origin we cannot at present definitely say.

SYMPTOMS. The symptoms of pernicious anæmia are chiefly those due to a profound anæmia manifested by weakness, lessened endurance, with dizziness, dyspnoea, palpitation of the heart, etc. The disease is not necessarily steadily progressive, as it is interrupted by waves of improvement. It may be either very acute or chronic in its course, as cases are known to die within a few weeks and others to live for several years. In probably a large percentage of the cases the body weight is preserved, and in a few others there is a loss of weight, and in some emaciation. There is a tendency to subcutaneous, submucous, retinal and other hemorrhages. Gastro-intestinal disturbance is very commonly present, and especially diarrhoea. The appetite is often poor or capricious. There may be a craving for acids, salts, or some other thing with decisive taste. The disease is associated with nervous phenomena in the great majority of cases; usually, however, subjective in character. There is often paræsthesia of the feet, sometimes of the hands. Cerebral disturbance in the form of lessened cerebration

may occur, and Minnich has observed fixation of the pupils, while Bemis, Müller and Nonne report cases of slight facial paralysis, or of one-sided paræsthesia, aphasia, etc.

The spinal cord lesions, which are now recognized as occurring in a small percentage of the cases, may appear as one of the earliest manifestations of the disease, or they may occur late, and may be manifested slightly or not at all up to the time of death. The spinal cord lesions, which will be discussed more fully later, do not always bear a direct ratio to the symptoms. In some instances, with no perceptible spinal cord changes, there may be marked subjective paræsthesias, and even slight ataxia and spasticity, while in other cases, with marked cord changes, the symptoms may be subjective only, and not in keeping with the marked changes in the cord. In the severer degrees of spinal cord lesions, when established, the course of the disease is usually rapid to a fatal ending.

Bastianelli divides the cases into two groups. One in which the pernicious anæmia is the predominant factor, and the cord lesion developing late, with only slight clinical manifestations, or possibly with only subjective disturbances. The second, in which the nervous phenomena develop first or coincidently with the anæmia, the nervous phenomena predominating and overshadowing the symptoms due to the anæmia, and the case rapidly developing into one of paraplegia, with flaccid muscles, loss of sphincter control, bed-sores, and death within a few weeks.

This makes a fairly good division for clinical use, but not all cases can be placed within the two divisions.

During the last few years I have had under direct observation thirty-six cases of pernicious anæmia.

ANALYSIS OF MY GROUP OF THIRTY-SIX CASES. Of these, 20 were males, and 16 females. The preponderance of males over females is unusual. The ages were as folThere were three in the second decennium, seven

lows:

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in the third, ten in the fourth, nine in the fifth, and seven in the sixth. The youngest was 24 years of age, and the oldest 69. In four cases tuberculosis existed in the family within two generations. In two patients carcinoma existed in the family within two generations. Three of the patients had suffered from syphilis. In two a severe attack of grippe was apparently the cause of an illness which finally developed into pernicious anæmia. One was overcome by smoke and gas at a fire in a large building. One suffered from exophthalmic goitre; fourteen had suffered from diarrhoea as the first manifestation of the disease. Diarrhoea had existed for three years as the longest time, and in one, after an acute attack of diarrhoea, the disease suddenly developed. stipation, obstinate in character, occurred in two. and vomiting were present in the majority of the patients at some time in the course of the early stage of the disease. Loss of appetite, amounting in some to complete anorexia, was present in all, and a capricious appetite existed in a few. In twelve repeated examinations of the stomach contents were made after test meals, and disclosed the absence of hydrochloric acid in all. There was enteroptosis of a severe degree in three. The association of grippe with pernicious anæmia has been noted by Bastianelli and by Putnam as a contributory factor in spinal cord lesions. all patients two or more complete blood examinations were made which gave the characteristic blood condition of pernicious anæmia. Retinal hemorrhages occurred in four; subcutaneous and submucous hemorrhages occurred in eight; epistaxis was a not uncommon factor, and in several bleeding of the gums was observed. Of the twenty male patients, in only three were the teeth bad, and in four only was the mouth in an unhealthy condition. Of the women, the condition of the mouth and teeth was notably bad. two cases no note was made of the condition of the teeth and mouth; in the remaining fourteen women, either the

In

In

teeth were decayed or the gums were infected in all. Of the thirty-six cases paræsthesia occurred early in the history of the case. It appeared simultaneously in the feet and hands in all of these cases, with the exception that in one it was confined to the toes of one foot and to the ulnar border of one hand. In four female patients the anæmia preceded the nervous phenomena by two years and four months, and in two men the nervous phenomena appeared one year and six months, respectively, after evidences of pernicious anæmia were established. In twenty-four of the cases the nervous phenomena were confined to subjective disturbance only, manifested by tingling, numbness, coldness, heat, formication, etc., of the hands or feet, or of both, and in one instance involving the entire lower extremities. Hyperæsthesia occurred in one. Disturbed temperature sense, inability to recognize quickly heat and cold, occurred in two, otherwise objectively the sensation of the feet and hands was normal. In these twenty-four cases the patients complained frequently of discomfort, of a sense of numbness and tingling which were most often present, and usually this condition remained, even when the patients were on a wave of improvement. In only one did it disappear during a wave of improvement, and it reappeared when a relapse occurred. In ten patients the subjective nervous disturbance was associated with a spastic, and usually with an ataxic condition, which grew steadily worse, and in three developed into complete flaccid paraplegia, with loss of knee jerk, loss of voluntary bowel and bladder control, and the development of oedema and bed-sores. One died while in a state of spastic paraplegia. Four are living with spastic ataxic paraplegia, and very troublesome subjective sensory disturbances. One case died with simple sensory disturbances only without ataxia, spasticity, or paraplegia, whose spinal cord showed dorso-lateral sclerosis. One died with all the evidences of insanity, but a post mortem was not obtainable.