Volume 1 — GENERAL DISEASES. (continued 21)

³¹ Hart, St. Bart's Rep., xii. 112.

The fauces appear to have been more or less inflamed in some epidemics; swelling of the parotid glands is an occasional occurrence, and sometimes they undergo suppuration. Aphthæ have also been met with.

The secretion of urine is not affected in any uniform manner. Sometimes it is diminished and sometimes increased in quantity. The latter symptom has occasionally long survived the disease. It retains its normal acidity. In rare cases either albumen or sugar has been detected; the former may have been due to the action of blisters of cantharides used in the treatment of the disease.

One of the most curious and unintelligible phenomena occasionally met with in this disease is a peculiar affection of the joints, which first was observed in this country. Jackson (1810 and 1813) wrote: "In some cases swellings have occurred in the joints and limbs. They have been very sore to the touch, and their appearance has been compared to that of the gout. The parts so affected feel as if they had been bruised. These swellings arise on the smaller as well as on the larger joints, and are often of a purple color." So Collins³² reports: "The joints sometimes become swollen, red, and tender; at other times red and painful without any swelling; while, again, intense pain and rapid enlargement from effusion have occurred unattended with redness. The joints most usually attacked are the knee, elbow, wrist, and the smaller articulations of the fingers and toes." In an epidemic which occurred in Greece in 1869 articular swellings similar to those of inflammatory rheumatism were observed.³³ These descriptions, which apply to some cases in most epidemics, are of more than casual interest, for they demonstrate conclusively, as we think, the truth which the whole history of the disease confirms—viz. that it is a systemic and not a local affection, and is dependent for its existence upon a specific poison which is absolutely unlike every other morbid poison known to pathology.

³² Dublin Quart. Jour., Aug., 1868, p. 170.

³³ Archives générales de med., Mai, 1883, p. 622.

The act of respiration is variously modified in this disease, as might, indeed, be expected from the seat and nature of the cerebro-spinal lesions. It is sighing, labored, and interrupted. Burdon-Sanderson describes its differences from the so-called Cheyne-Stokes respiration; it is, he says, "marked by a slow, labored inspiration, followed by a quick expiration and a long pause." When opisthotonos is very great and persistent, it necessarily interferes with the dilatation of the lungs, and leads to oedema of those organs, and even to sanguineous effusions into them. Pneumonia is not an unusual complication of the disease when it prevails in cold weather.

The distinguishing characters of the pulse are diminished force and volume, and a tone so much impaired that slight causes produce extreme variations in its rate and rhythm. If the disease be a fever, as is by some maintained, then it is the only fever in which the pulse-rate is often far below the normal, and at the same time neither full nor tense, unless transiently and in altogether exceptional cases. In no other disease attended with inflammation do the rate and quality of the pulse vary so greatly within short intervals. It may be said, in general terms, to be variable in rate and strength even in the most sthenic cases of the disease, and in those which tend to a fatal issue to be small, thready, weak, intermittent, or imperceptible for a longer or shorter time before death. It is no uncommon thing for the pulse-rate at the beginning of an attack to fall as low as 40, or even 27, and afterward rise to 120 or even more, in a minute, without necessarily indicating a fatal issue. Muscular exertion, rising from a recumbent posture, etc., will sometimes double its frequency, besides producing irregularity. Read, describing the pulse as he observed it in Boston in 1873-74, speaks of cases in which "both the rhythm and the force of the beats are entirely destroyed; ... one moment, while beating very fast, it will suddenly drop to a much lower rate.... These conditions also may outlast apparent convalescence." Some fatal cases are attended by distressing palpitations of the heart.

Nothing is more remarkable in the early histories of this affection than their unanimous statement that it is not distinguished by a febrile temperature. It is true that the observers of those days had not the advantage of using clinical thermometers, but they were too nearly agreed in their judgments and harmonious in their descriptions to permit any serious doubt of the substantial accuracy of their conclusions, which were expressed in such terms as these: "A diminution of heat may be considered as among this most striking symptoms of this disease" (Strong); or, "the temperature never exceeded the standard of health in more than three or four cases, ... and a great majority of the patients had no fever at all" (Miner); or, again, "A high febrile movement took place only in a limited number" (Gilchrist); or, "The heat of the surface was less in all cases than is usually observed in acute diseases" (Jenks). It will be observed that these statements, and very many others which agree with them, were founded upon the perception of the patients' temperature by the hand, which was of course applied to the most accessible parts of the body—the face, neck, arms, and hands—but they have more real value and significance than the more recent measurements taken in the mouth, axilla, rectum, or vagina, for we know that, however valuable the temperatures of these parts may be for comparative studies, they do not really indicate the condition of the individual who presents them. It is a familiar fact that the difference of temperature in cholera when taken in the rectum and the axilla may be 4° F., or even more than this.

Since the thermometer has been used in the study of epidemic meningitis greater accuracy of results has been attained, and yet the general statements of the earlier observers have been confirmed. Thus, Githens has shown that the temperature of the body in this disease is lower than that recorded of any other fever or inflammatory affection; the average, indeed, of his cases was lower by four or five degrees than that of typhus or typhoid fever, pneumonia, etc. In 2 cases only did the thermometer in the axilla reach 105°. The highest temperature in 15 cases was between 104° and 105°; in 12, between 103° and 104°; in 7, between 102° and 103°; in 6, between 101° and 102°; and in 2 it was below 100°.³⁴ Tourdes, Niemeyer, and others have noted the slight rise of temperature during the first and second days of the attack, and Wunderlich found fever of very unequal degrees and with very variable maxima, but the highest temperatures were observed by him as well as others in fatal cases and immediately before death. In one instance it reached 107.5° F. Burdon-Sanderson and others have found that an increased temperature always attended exacerbations of pain. Von Ziemssen gives the average temperature as varying from 100.4° to 103° F., but with variations between higher and lower points, and particularly notes the persistence of a normal temperature while the other symptoms are undergoing a variety of changes, as well as the fact that, unlike other febrile affections, this disease has no representative temperature curve. In his clinical observations Hart found for several successive days as much as six degrees of difference between the morning and evening temperatures. A morning rise for several days was noticed in four cases, and usually there was no relation between the pulse and the temperature, nor any uniformly between the temperature and the gravity of the attack.³⁵ But not rarely it has been noticed that the daily exacerbations, if any, did not occur in the afternoon, but with great irregularity, so that the maxima and minima might occur on successive days and at the same hour of the day. Dr. J. L. Smith, whose thermometric observations in this disease seem to have been carefully made, used the thermometer in the rectum, and thus obtained temperatures higher that the average of other observations, such as 105.⁴/6° to 107.²/6° in several cases. Yet he found the fluctuations of rectal temperature remarkable, though less so than the surface temperature, of which he states that sometimes it rose above or fell below the normal standard several times in the course of the same day.

³⁴ Amer. Jour. of Med. Sci., July, 1867, p. 38.

³⁵ St. Bart's Reports, xii. 112.

Nothing can be more irregular, uncertain, or various than the eruptions and other cutaneous symptoms that have been met with in this disease. When it first appeared in New England a large proportion of the cases, and especially of the grave cases, exhibited petechial eruptions and ecchymotic spots, whence the disease presently received the name of spotted fever. Yet even then, North and the other historians of its epidemics were careful to state that spots on the skin were by no means characteristic of the disease, and very often were not present at all, especially in cases that terminated favorably. Woodward, for example, wrote (1808): "An eruption on the skin so seldom appeared that it could no longer be considered a characteristic symptom of the disease." In various American local epidemics an eruption of some kind seems to have existed in about one-half of the cases. In one that we observed in the Philadelphia Hospital no eruption whatever was observed in thirty-seven out of ninety-eight cases. In the epidemic at Chicago in 1872, N. S. Davis says:³⁶ "About one-third of the cases presented some red erythematous spots" between the third and the seventh day. In mild cases they were few and bright red; in grave cases, darker and larger, with some swelling of the skin; and in the worst cases, purple spots one or two or more inches in diameter. In that of Louisville,³⁷ Larrabie states that the eruption "was generally herpetic in its character, and accompanied by sudamina; but in several instances an urticarious eruption suddenly appeared and disappeared." Nothing is said of petechiæ or ecchymoses. In the New York epidemic of 1873³⁸ the skin in grave cases presented dusky mottlings, especially when the animal temperature was reduced; also a punctated red eruption, bluish spots a few lines in diameter, and large patches of the same color. Herpes also was common. It is chiefly in cases of a malignant type and rapid and fatal course that ecchymoses have been observed. Of this statement illustrations will be given in the paragraph relating to the duration of the disease.

³⁶ Louisville Med. Jour., June, 1872, p. 705.

³⁷ Louisville Med. Jour., Dec., 1872, p. 782.

³⁸ Amer. Jour. of Med. Sci., Oct., 1873, p. 329.

In continental European epidemics of meningitis the proportion of cases in which a general eruption existed seems to have been smaller than it was in this country. In the Geneva epidemic of 1805 a considerable number of cases at the point of death presented purplish spots, some earlier than this, and some after death only. In the Neapolitan epidemic of 1833, and in that which occurred in Dublin in 1867-68, ecchymoses were often present, and in a very marked degree. Stokes and Banks mention that in some rare instances the spots ran together and coalesced over some portions of the body, so as to cover a large extent of the skin and render it completely black, as though it were wrapped in some dark shroud. The entire right arm and half of the right side of the chest in one case, and in the other the whole of the lower portion of one leg and foot, were thus affected.³⁹ In Strasburg, on the other hand, only three cases of petechiæ were observed by Tourdes; at Rochefort and Versailles, in 1839, they were rarely noticed; at Gibraltar, in 1844, they do not seem to have been observed; in 1848-49, at the Val de Grâce Hospital (Paris), they appear not to have attracted attention; and at Petit Bourg they were not noticed, although the state of the skin was fully described. In Prussia, in 1865, neither Burdon-Sanderson nor Wunderlich mentions petechiæ or vibices as occurring during life; and Hirsch, after noting their occasional presence, is obliged to draw upon American authors for an account of them.

³⁹ Dublin Quart. Jour., xlvi. 199.

Of the eruptions other than petechiæ and ecchymoses, several of which have already been mentioned, it is necessary to take some notice here. They are, chiefly, and in general terms, exanthems, including erythema, roseola, and urticaria, and in addition herpes, particularly of the lips. The last has no special relation to this affection, as it is met with in almost every febrile disease, but it has sometimes extended to the whole face in this one. The former may be connected pathologically either with the altered condition of the blood or with the irritation produced by the exudation in the spinal nervous centres. They have frequently been compared to measles and to scarlatina, but sometimes they have assumed the form of bullæ. Thus, in the case of a child four years old, described by Grimshaw,⁴⁰ an eruption of pemphigus occurred over the whole body. Jackson long before had mentioned, as one of the eruptions belonging to this disease, "large bullæ, as if produced by cantharides." Jenks described "large elevated spots of a very dark color, presenting outside of the dark color a blistered appearance." In some cases gangrene of the skin has been observed when the spots have been exceptionally dark, and occasionally has been produced by pressure.

⁴⁰ Jour. of Cutaneous Med., ii. 37.

The cause of death in many of the more rapid cases is coma, which is often preceded by convulsions, especially in children; but in many others, even when attended with all the marks of dissolution of the blood, consciousness may be but slightly impaired until the actual imminence of death. In many other cases, which are fatal in the midst of an attack with spinal symptoms, death is due to asphyxia, partly owing to pressure on the medulla oblongata, and partly to the interference with the respiratory act due to this pressure, and occasioning excessive bronchial secretion. Again, death may occur through a gradual exhaustion of the powers of life, without marked spasm, blood-change, or complication. In these cases also the intelligence remains unimpaired almost until the moment of dissolution. Death is not very rarely due to pneumonia, and when the disease is greatly prolonged or the convalescence from it is imperfect a fatal termination by dropsy of the brain is still among its dangers.

Hirsch once declared that the duration of epidemic meningitis "is between a few hours and several months," and, however hyperbolical the phrase may seem, it is quite accurate. Such inequalities are more characteristic of acute blood diseases than of inflammations, and in this case the coexistence of elements of both kinds doubtless accounts for the extreme irregularity of the symptoms and duration of the attack. The early American writers insisted strongly on this as a characteristic feature of the disease. They record an unusually large proportion of cases that were fatal within the first day, and even after an illness of five hours, although they agree that the most usual date of death was between the fourth and seventh days—a result that has been confirmed by subsequent observation. Dr. N. S. Davis gives the duration of the disease, as seen by him, as between twenty hours and twenty-eight days. Out of 469 fatal cases in the city of New York in 1872, 334 are said to have terminated within eleven days, and of this number 270 were fatal in the first six days of the attack, including 52 who died on the first day, and 51 in from one to two days. It is perhaps worthy of note that while from the eleventh to the fourteenth day only 11 deaths occurred, 20 took place on the fourteenth and fifteenth; and while from the fifteenth to the twenty-first day only 16 died, yet from the twenty-first to the twenty-second 12 deaths were reported. This would seem to indicate a peculiar danger on the days represented by multiples of seven. Of cases that recover, the duration is even more indefinite than that of fatal cases, owing to complications that occur in many, and especially such as involve the cerebro-spinal centres. When death takes place within a few hours it usually, if not always, is attended with symptoms that denote a disorganization of the blood. In 1864 we attended a young man previously in perfect health, but who died in twenty-one hours after the first seizure. His mind was unclouded throughout his brief but fatal illness. Within seven hours of death a purpurous discoloration of the skin began, and about an hour before that event the surface everywhere assumed a dusky hue. The forearms and hands were almost uniformly purple and the face turgid; many ecchymotic spots on the trunk and lower limbs were nearly black and measured one or two inches in diameter.⁴¹ In the case of a child of five years death in convulsions took place after an illness of ten hours, the skin presenting purpurous spots, some of them very large and of a deep bluish livid hue. On post-mortem examination there was not the slightest appearance of any meningeal lesion, except a few dark spots like sanguineous effusion under the arachnoid. The heart was full of dark blood in a semi-coagulated state, and the white corpuscles were three times as numerous as the red.⁴² A case is reported by Gordon⁴³ in which the entire duration of the illness until death was five hours. This is probably the shortest case on record. A lady aged twenty-two years died in sixteen hours, the skin covered with livid ecchymoses, some of them measuring an inch or an inch and a half in diameter.⁴⁴

⁴¹ Amer. Jour. of Med. Sci., July, 1864, p. 133.

⁴² Dublin Quart. Jour., 1867, ii. 441.

⁴³ Loc. cit.

⁴⁴ Med. Press and Circular, May, 1866. For other cases see ibid., pp. 296, 298-300.

The character of the convalescence from epidemic meningitis must evidently be affected by the causes that determine its duration, the grade of the disease, the development and extent of the lesions, etc.; but it is certain that, except in those imperfect and, as it were, shadowy cases which denote a very slight action of the morbid cause, its subjects do not recover rapidly. The essential lesion of the fully-formed disease requires time for its removal, just as in typhoid fever the intestinal ulcers are often slow of healing, and hence become a cause of tardy recovery and even of unlooked-for death. The convalescence, then, from the disease we are now studying is slow and irregular, is attended often with debility and emaciation, and sometimes with persistent headache, neuralgia, convulsions, stiffness of the neck and pain in moving it, hyperæsthesia of portions of the skin, palpitation of the heart, dyspepsia, etc. Relapses are very far from being uncommon.

Among the causes of tardy convalescence in this disease are those lesions and disorders which may be embraced by the term sequelæ. Impaired vision, due to various affections of the eyes, has already been considered among the symptoms proper of the disease, but they are not infrequently developed after the acute attack has subsided. Thus, in a case reported by Larrabie:⁴⁵ "Just as convalescence seemed beginning the left eye became affected in all its parts, with entire loss of vision and also complete deafness. After a short remission hydrencephaloid symptoms appeared, followed by the same changes in the hitherto sound eye, complete blindness and deafness, general cachexia and marasmus, rigid flexion of the right limbs, and death by exhaustion at the end of sixteen weeks." The impairment of hearing, which also was described as a symptom of the acute attack, is apt to become more marked after the acute stage has passed by, and, as before stated, is very often permanent. Occurring in young children, it then involves deaf-mutism. It is in many cases associated with defective vision, weakness or loss of memory, mania, impairment of intelligence, persistent pains in the head or chronic hydrocephalus. Sometimes to one or more of these symptoms is added more or less general paresis or complete paralysis. Southhall⁴⁶ mentions the case of a child two years old whose attack was followed by incomplete paralysis, and death at the end of eight months with softening of the brain. Gordon thus describes the conclusion of a case: "The man has gradually passed into a state of almost organic life; he eats, drinks, and sleeps well; he passes solid feces and urine without giving any notice, yet, evidently, not unconsciously; ... he seems to understand, but cannot answer; ... he can draw up his legs and arms, but he cannot use his hands at all." Hirsch has remarked that disorders of speech are met with, due apparently to an inability to articulate certain sounds. Von Ziemssen regards chronic hydrocephalus as not a rare consequence of epidemic meningitis, and as one not absolutely or immediately fatal. Its symptoms include severe paroxysmal pain in the head or neck or extremities, with vomiting, loss of consciousness, convulsions, and involuntary evacuation of excrements. Between the paroxysms, which sometimes occur periodically, the patient generally suffers from neuralgic pains, hyperæsthesia, and various motor and even mental disorders; but in other cases the intervals are free, or nearly so, from all morbid manifestations. Davis (1872) and many others speak of severe neuralgic pains following this disease; according to Dr. D., they are most frequent at the heads of the gastrocnemii muscles, in the abdomen, and the head; a very fretful disposition, variable appetite, and disturbed sleep are often observed. Relapses have been noticed in almost all the epidemics, and it seems probable that they are often due to the influence of accidental exciting causes, mental or physical, in renewing the inflammation around the cerebro-spinal lesions. Miner (1825) remarked that they were most apt to occur within the first week, but that when the disease had once run its course there were very few relapses during convalescence. But, he adds, there were several repeated attacks after the most perfect recovery, and several of the patients had had the disease the preceding year.

⁴⁵ Richmond Journal of Med., Dec., 1872, p. 779.

⁴⁶ Ibid., Aug., 1872, p. 141.

Like other epidemic diseases, meningitis presents itself with every possible degree of gravity between that of a slight indisposition and that of a malignant and deadly malady. The mortality in a number of epidemics compared by Hirsch varied between 20 per cent. and 75 per cent. It changes with the locality. Thus, nearly at the same time that the death-rate from this disease in Massachusetts was 61 per cent., it was but 33 per cent. in the Philadelphia Hospital. In 1872 the whole number of deaths caused by it in Philadelphia was 133, while at St. John's College, Little Rock, Ark., 21 cases out of 29 were fatal (Southhall). It differs, also, at different periods; for while ten epidemics in various places, occurring between 1838 and 1848, presented an average mortality of 70 per cent., a similar number, occurring between 1855 and 1865, gave an average mortality of only 30 per cent. It must, however, be confessed that such statistics cannot be relied upon as accurate, for in private practice many cases occur that are never reported unless they end fatally.

MORBID ANATOMY.—The lesions found after death from epidemic meningitis consist essentially of congestion or inflammation of the cerebro-spinal meninges, but they also include in many cases hemorrhage, serous effusion, plastic exudation, and tissue-changes in the brain and spinal marrow, and in many other cases an impaired constitution of the blood. As the signs of the latter, and not the former, alterations are met with in the more malignant cases, it is evident that, looking at the disease as a whole, it must involve a toxic element of whose operation the various post-mortem lesions are only effects. These lesions, on the whole, vary with the type of the disease, and also with its duration, but some are chiefly met with in cases of a malignant and others in cases of an inflammatory type.

The exterior of the body after death in the early stages of this disease almost always presents the marks of transudation of the contents of the blood-vessels. The dependent parts of the body exhibit large livid patches or a uniform discoloration of the same hue. In acute cases the muscles are more deeply colored than natural, and when the attack is prolonged they are said to have their cohesion impaired by fatty degeneration. Congestion of the brain is an unfailing accompaniment of the first stage of the disease; its blood-vessels are all distended with dark blood; the sinuses of the dura mater are usually filled with coagula of the same hue, though sometimes very dense. Serum abounds in the arachnoid cavity and in the ventricles of the brain; it may be clear or milky, and sometimes it is quite purulent. It is alleged by one reporter that no less than three pints of turbid serum escaped in a case in which, however, death did not occur until the thirty-fifth day. Craig found eight and twelve ounces of a limpid fluid in two cases; and Tourdes found pus in more than one-half of his cases, either unmixed or forming a milky liquid. J. L. Smith refers to the case of an infant who had the disease at the age of five months, and two months subsequently great prominence of the anterior fontanelle, and other symptoms which indicated the presence of a considerable amount of effusion within the cranium. In a case in Dublin,⁴⁷ there was no meningeal lesion except in a "few dark spots like sanguineous effusion under the arachnoid." White⁴⁸ mentions the case of an adult that terminated fatally in thirty-six hours, in which the vessels of the pia mater were very much congested, and sanguineous effusions existed above and below the cerebellum, and a clot of blood three inches long and external to the theca extended downward from the lowest portion of the medulla oblongata. In all of these instances, then, congestion, the first stage of inflammation, existed. That such was its real nature is proved by what follows.

⁴⁷ Dublin Jour., July, 1867, p. 441.

⁴⁸ Med. Record, iii. 198.

The most characteristic lesion is a fibrinous or purulent exudation in the meshes of the pia mater. American physicians described it as early as 1806 in such terms as these: "The dura mater and pia mater in several places adhered together and to the substance of the brain; ... between the dura mater and the pia mater was a fluid resembling pus" (Danielson and Mann). In 1810, Bartlett and Wilson found "an extravasation of lymph on the surface of the brain;" and in the same year Jackson and his colleagues, after describing the congestion and serous effusion found within the cranium "in those who perished within twelve hours of the first invasion," state that the arachnoid and pia mater present an effusion between them of "coagulated lymph or semi-purulent lymph" both on the convexity and at the base of the brain. These descriptions correspond in all respects with those of Mathey relating to the epidemic at Geneva in 1805, for he says: "The meningeal blood-vessels were strongly injected. A jelly-like exudation tinged with blood covered the surface of the brain; ... on its lower surface and in the ventricles a yellowish puriform matter was found." Such lesions have been described by a long line of observers—by Wilson in 1813, Gamage in 1818, Ames and Sargent in 1848; by Squire, Upham, and a host of others since 1860 in the United States, and by Tourdes, Gilchrist, Ferrus, Wilks, Gordon, Banks, Gaskoin, Niemeyer, Burdon-Sanderson, and many more in Europe.

It is evident, therefore, that in a certain number of fatal cases only sanguineous congestion of the membranes of the brain and spinal cord are found, and in certain others—constituting, it may be added, nine-tenths of the whole number—evidences exist of cerebro-spinal meningitis. Hence the natural conclusion is that the congestive lesions represent the first stage of a process which if prolonged and perfected occasions the lesions peculiar to inflammation. For the development of the latter two factors would seem to be essential—not only a fibrinous condition of the blood, but also sufficient time for exudation to occur. But when we come to study the actual results of examinations post-mortem, it is found that the duration of the attack does not determine absolutely the nature of the lesions. On the one hand, in a case which terminated fatally after a week's illness there was found reddish serum between the arachnoid and the pia mater and in the lateral ventricles, with intense injection of the pia mater of the base, medulla oblongata, and upper part of the spinal cord, but no exudation of lymph.⁴⁹ And, on the other hand, numerous cases have been published in which, although death occurred within twenty-four hours from the onset of the attack, coagulated lymph and also pus were found upon the brain and spinal marrow. For example, during the winter of 1861-62, in the army, that then lay near Washington, D.C., a soldier was attacked with a chill, severe fever, and headache, followed by opisthotonos and repeated convulsions before his death, which occurred in about twenty-four hours. No eruption or discoloration of the skin is mentioned in the history. On examination there was found beneath the arachnoid a thin layer of lymph and abundant exudation over the posterior lobes of the cerebrum, and also at the base of the brain and on the medulla oblongata.⁵⁰ In a case reported by Gordon⁵¹ the entire duration of the illness was under five hours, and after death the cerebral arachnoid was more or less opaque, and in some spots had a layer of very thin purulent matter beneath it. And, again, not only may the symptoms belonging to blood-dissolution be consistent with a certain prolongation of life, but also with decidedly inflammatory tissue-changes. Thus, in another case of Gordon's the duration of the illness was at least six days, and the patient presented all the characteristic symptoms of the disease, including "a most wonderful and uniform curve of the spine and head backward," "spots black as ink," "bullæ which rapidly became opaque and dusky," "herpetic eruption, etc." After death the body had a very frightful appearance. It was still prominently arched forward. It was of a dusky blue color, with a copious eruption of black spots of various sizes, and one or two of them were gangrenous.... When the theca vertebralis was opened purulent matter flowed out, and a purulent effusion was found in patches on the brain. The cerebral arachnoid was all opaque, the lateral ventricles were filled with serum, and the blood in all the cavities was very fluid and dark colored. From all that precedes, therefore, it must be inferred that the nature of the lesions in this disease depends not on the type alone, nor on the duration merely, of the attack—that a very brief course is compatible with marked inflammatory lesions, and a prolonged one with profound alterations in the condition of the blood. In other words, it seems that there must be something besides the appreciable lesions that influences, if it does not determine, the issue of an attack of this affection. While bringing forward prominently this proposition, and the facts on which it rests, we have no intention of under-estimating the relative significance of the two most conspicuous types of the disease, the purely inflammatory and the adynamic, or calling in question the fact that the evolution of the former is most usually comparatively slow and regular, and of the latter rapid and irregular. In the one, when death takes place early, congestive changes are found, and when later these have merged into exudative lesions; in the other or adynamic cases congestion and liquid transudation prevail, and the results of complete inflammation are seldom seen. When the disease has been very much prolonged the exudation becomes tough, adherent, and shrivelled.

⁴⁹ Davis, Richmond Med. Jour., June, 1872, p. 709.

⁵⁰ Frothingham, Amer. Med. Times, Apr., 1864, p. 207.

⁵¹ Dublin Quart. Jour., May, 1867, p. 409.

The brain-tissue has generally been found softer than natural, and, although in some cases this diminished consistence might be attributed to post-mortem changes, yet on the whole it must be associated with the inflammatory lesions of the meninges. As a rule, it is greater the longer the attack has lasted, and is by no means equally diffused, but is more marked where the meningeal alterations are greatest. Ames found softening in nine out of eleven cases, and chiefly in the cortical substance, but also in the fornix and septum lucidum; and Chauffard states that in protracted cases "the interior surface of the ventricles, the fornix, and septum lucidum, were reduced to a pultaceous and creamy consistence." But it is by no means true that softening is met with in all cases of long duration.

The lesions of the spinal marrow and its membranes correspond with those of the brain. The dura mater is often very dark, its blood-vessels engorged, its arachnoid cavity distended with serum more or less bloody, turbid, or purulent. Two ounces of pus have been removed from it through a puncture. Fibrinous and purulent exudation fills the meshes of the pia mater, and is usually most abundant in the cervical and dorsal portions, and generally upon the posterior rather than upon the anterior surface of the organ; but sometimes large accumulations of lymph and pus are found at the lower end of the cord. Gordon⁵² relates of a case that "when an opening was made into the lower part of the theca vertebralis purulent matter flowed out, and the entire surface of the pia mater was covered with a coating of thin purulent matter, which, like a thin layer of butter, remained adherent to it." Occasionally the cavity of the spinal arachnoid contains blood. Softening of the spinal cord has been often noticed. Chauffard states that in some cases of particularly long duration it was reduced to a mere pulp, and he adds, "in the place of portions of the spinal marrow, completely destroyed, was found only a yellowish liquid, or the empty membranes fell into contact where it was wanting." Similar disorganization has been described by Ames, Klebs, and others. Fronmüller reports the case of a girl aged fourteen years in whom the central canal of the spinal cord was distended with pure pus.

⁵² Dublin Quart. Jour., xliii. 414.

The lesions of the internal auditory apparatus consist of softening in the fourth ventricle and of the root of the auditory nerve, yet such lesions are said to have been found even when no defect of hearing had existed. In other cases in which deafness did occur the lesions consisted of inflammatory changes in the cavity of the tympanum and suppuration of the labyrinth. They probably arose from an extension of inflammation from the pia mater along the trunk of the auditory nerve (Von Ziemssen). In like manner, the inflammatory and destructive changes in the eye which have been elsewhere described arise from an analogous cause affecting the optic nerves.

It is unnecessary to dwell upon the condition in which other organs are found after death from epidemic meningitis. In cases that present a typhoid type, and even in such as are rapidly fatal with ecchymotic discoloration of the skin, the various organs present no distinctive tissue-change, but only such engorgement as is common to all diseases of a similar type. It deserves to be particularly mentioned that in this affection the spleen is not enlarged, as it always is in a greater or less degree in diseases whose primary stage involves an altered condition of the blood. This fact becomes all the more important in view of the remarkable contrast which the constitution of the blood presents in epidemic meningitis and in various typhous affections.

The state of the blood in this disease is one of peculiar interest, dominating as it does its whole pathology and determining its nosological position. It is the blood of a phlegmasia rather than of a pyrexia. This fact was early established by American physicians who observed the disease, and the opportunities for doing so were not wanting, since venesection was used by every one who treated it. In 1807-09 a rapidly fatal case or two was found in which the "blood was darker and had a larger proportion of serum than usual," but in others "it did not present any uncommon appearance, and no inflammatory buff, nor was it dissolved" (Fish). In 1811, Arnell stated that "the blood drawn in the early stage appeared like that of a person in full health; there was no unusual buffy coat, neither was the crassamentum broken down or destroyed." In the epidemic studied by Mannkopff (1866) he found that blood obtained by venesection gave a clot with a thick buffy coat. Andral, seeking to establish the law that in every acute inflammation there is an increase in the fibrin of the blood, remarks that in a case of cerebro-spinal meningitis it was very marked.⁵³ Ames states that "the blood taken from the arm and by cups from the back of the neck" "coagulated with great rapidity." "Its color was generally bright—in a few cases nearly approaching to that of arterial blood; it was seldom buffed; in thirty-seven cases in which its appearance was noted it was buffed in only four." Analyses were made in four cases, "the blood being taken early in the disease from the arm, and was the first bleeding in each case. They furnished the following results:

Fibrin. Corpuscles.

I 6.40 140.29

II 5.20 112.79

III 3.64 123.45

IV 4.56 129.50

The first was from a laboring man thirty-five years old; the second from a boy twelve years old, while comatose; and the two others from stout women between thirty and thirty-five."⁵⁴ Tourdes, whose analyses follow, states that "blood drawn from a vein was rarely buffed; if a buffy coat existed, it was thin, and generally a mere iridization upon the surface of the clot."⁵⁵

Fibrin. Corpuscles.

I 4.60 134.00

II 3.90 135.54

III 3.70 143.00

IV 5.63 137.84

Maillot gives, as the result of an analysis of six cases, an increase of fibrin to six parts and more in a thousand. This summary represents, as far as is known, all of the analyses of blood taken from living patients in this disease, and it shows that in every case the proportion of fibrin exceeded that of healthy blood, and corresponded exactly to that observed in the blood of inflammatory diseases, while the proportion of red corpuscles varied within the normal limits. How different is this condition of the blood from that of typhus fever, in which there is a marked diminution of fibrin, and a falling off in the red corpuscles as well, or from that of typhoid fever, in which neither element declines until the disease affects the body by inanition! (Murchison).

⁵³ Path. Hæmatology, p. 73.

⁵⁴ New Orleans Med. and Surg. Jour., Nov., 1848.

⁵⁵ Epidemie de Strasbourg, p. 160.

In regard to the condition of the blood after death the historians of the disease are not so well agreed; nevertheless, the preponderance of the testimony is in favor of the statement that the blood presents appearances resembling those belonging to the continued fevers rather than to the inflammations. It is true that even in this the agreement is neither general nor complete. Tourdes, for example, states that in an autopsy "the blood was remarkable for the abundance and toughness of the fibrinous clots," but the greater number have reported it as being dark and liquid. Such was its condition in the epidemic which we studied at the Philadelphia Hospital in 1866-67, and it has been correctly described by Dr. Githens as follows: "The blood was fluid, of the color and appearance of port-wine lees; under the microscope the corpuscles were shrivelled and crenated, and there was a space apparent between them as they were arranged in rouleaux. There were in two cases white, firm, fibrinous heart-clots extending through both ventricles and auricles and into the vessels leading to and from the heart."⁵⁶ It may be added that the red corpuscles are often crenated and shrivelled when the case has been protracted, and it has been stated—from limited observation, indeed—that "the white corpuscles are three times more numerous than the red."⁵⁷ The blood has been scrutinized to discover, if possible, some of those bodies which are judged by Koch and his disciples to differentiate general diseases, but it is stated that the investigation has been without definite result.⁵⁸

⁵⁶ Amer. Jour. of Med. Sci., July, 1867, p. 23.

⁵⁷ Dublin Quart. Jour., May, 1867, p. 441.

⁵⁸ Jaffé, Phila. Med. Times, xii. 599.

It does not seem difficult to reconcile the conflicting statements now given of the condition of the blood in epidemic meningitis. One of them points to an excess and the other to a loss of the spontaneously coagulable element of the blood. It is evident that venesection, which was necessary for procuring the living blood for analysis, would only be performed when the type of the disease authorized it—that is, when the type was sthenic; whereas the blood examined after death had necessarily undergone changes which tended to, if they did not actually, occasion death. Hence we find among the former cases, when fatal, the most extensive and massive exudation, and always among the latter less evidence of inflammation, but, on the other hand, a greater or less manifestation of those appearances which denote a loss of the vitality and organization of the blood. In the one case death may fairly be attributed, above all other causes, to the pressure upon, and the disorganization of, the cerebro-spinal organs essential to life; in the other, primarily, to the death of the vital elements of the blood produced by the specific cause of the disease. It is probable that the post-mortem fluidity of the blood exists under two conditions. In the one the morbid cause is powerful enough from the very commencement rapidly to destroy the life of that fluid, and in the other it acts less violently, but continuously, to exhaust the powers of life.

Our conception of the pathology of epidemic meningitis is implicitly contained in the foregoing discussion. Of its essential cause and of the conditions that call it into existence nothing whatever is known. The disease is most probably due to some atmospheric agency that is capable of acting at the same time upon widely separated localities. Its specific cause appears to enter the blood first of all, and doubtless through the lungs, and to be capable of destroying life by its action upon the blood alone. Failing this effect, its force is spent upon the cerebro-spinal pia mater, and it may become fatal by the mechanical interference of the products of inflammation with the nutrition of those parts of the central nervous system which are essential to life. An inflammatory and a septic element together constitute the fully-developed disease; either may be in excess and overshadow the other. According to the relative predominance of one or the other, the disease assumes more of a typhoid or more of an inflammatory type, and it is doubtless this diversity in its physiognomy, as well as in the lesions that attend it, which has led to the most opposite doctrines respecting its nature and its nosological affinities.

DIAGNOSIS.—The most distinctive phenomena of epidemic meningitis are suddenness of attack and rapidity of development of the following symptoms: acute pain in the head, neck, spine, and limbs; faintness, vomiting; stiffness or spasm of the cervical or spinal muscles; hyperæsthesia of the skin; delirium, alternating with intelligence and merging afterward into dulness or coma; occasional convulsive spasms; paralysis of the face or of one side of the body. The evidences of associated blood-poisoning are, the epidemic prevalence of the disease, various eruptions upon the skin (herpes, roseola, petechiæ, etc.), ecchymoses, debility out of proportion to the evidences of local disease, redness of the eyes, foulness of the tongue and mouth, and more or less of the other conditions which characterize the typhoid state. To these features must be added the rate of mortality, which is greater in most epidemics of meningitis than that of any disease with which it is liable to be confounded.

It is distinguished from sporadic meningitis by the fact that the latter disease is never primary, but is always either an epiphenomenon of some other and previous malady (various fevers and chronic blood diseases) or is traumatic in its origin. The thermometer readily distinguishes it from various functional nervous affections, chiefly hysterical, in which the temperature remains normal.

From typhoid fever it differs as widely as possible by its rapid onset, the exquisite pain in the head, the neuralgic pains, the opisthotonos, and the convulsions. The alternate delirium or coma and clearness of mind in meningitis contrast with the persistent hebetude, stupor, or muttering delirium and the muscular relaxation in typhoid fever. The sordes on the tongue, the diarrhoea, the meteorism, the intestinal hemorrhage of the latter, instead of the moist or merely dry tongue and the transient vomiting and torpid bowels of the former; high or continuous fever on the one hand, slight or variable increase of temperature on the other; diffluence of blood in the one and an increase in the proportion of its fibrin in the other; in the one suppurative inflammation of the cerebro-spinal meninges, in the other specific lesions of the intestinal and mesenteric glands,—these, as well as the very different modes of origin of the two affections, draw a broad and manifest line of distinction between them.

It would scarcely be necessary to point out the contrasts between epidemic meningitis and typhus fever were it not that, notwithstanding the abundance of instruction on the subject in medical treatises and lectures, a large number of physicians confound typhus fever, typhoid fever, and the typhoid state of inflammatory diseases with one another. The confusion was intensified at one time by designating the disease we are studying as spotted fever—a term originally applied and properly belonging to typhus fever (typhus petechialis). It is true that New England physicians soon became aware of their error, which was distinctly pointed out and condemned by North, Strong, Miner, Foot, Fish, and others in the early part of this century. A similar error was at first committed both in Ireland and England, but was corrected by maturer experience. In order to contrast the two diseases as strongly as possible, we place their distinctive features side by side in the following table:

EPIDEMIC MENINGITIS. TYPHUS FEVER.

A pandemic disease. Occurs simultaneously in places remote from one another and without intercommunication. An endemic disease, due to local causes and spreading by intercommunication.

Attacks all classes of society. Is never primarily developed by destitution, squalor, or defective ventilation. Attacks the poor, filthy, and crowded alone.

Is not contagious. Contagious in a high degree.

Attacks more males than females. Both sexes equally affected.

Attacks more young persons than adults. More adults than young persons.

Generally occurs in winter. Epidemics irrespective of season.

Eruptions are absent in at least half of the cases; they occur within the first day or two. Eruption rarely absent, and appears about the fifth day.

The eruptions are various; they include erythema, roseola, urticaria, herpes, etc. Ecchymoses are common. Eruption always roseolous, and then petechial. Ecchymoses are rare.

Headache is acute, agonizing, tensive. Headache dull and heavy.

Delirium often absent; often hysterical, sometimes vivacious, sometimes maniacal. Generally begins on the first or second day. Delirium rarely absent; usually muttering. Rarely begins before the end of the first week.

Pulse very often not above the natural rate; often preternaturally frequent or infrequent. Is subject to sudden and great variations. A slow pulse exceedingly rare. Its rate usually between 90 and 120.

"The temperature is lower than that recorded in any other typhoid or inflammatory disease." It is also very fluctuating. The temperature is always elevated, and does not fall until the close of the attack. "The skin is hot, burning, and pungent to the feel."

The body has no peculiar smell. The mouse-like smell is characteristic.

The tongue is generally moist and soft, and if dry is not foul. Sordes on teeth rare. The tongue is generally dry, hard, and brown, and the teeth and gums fuliginous.

Vomiting is an almost constant and urgent symptom, especially in the first stage. Vomiting is rare and not urgent.

Pains in the spine and limbs of a sharp and lancinating character are usual. The pains, if any, are dull, and apparently muscular.

Tetanic spasms occur in a large proportion of cases and within the first two or three days. They are due to an exudation on the medulla oblongata and spinalis. Tetanic spasms are unknown in typhus. Convulsions sometimes occur, due to pyæmia.

Cutaneous hyperæsthesia is a prominent symptom. The sensibility of the skin is generally blunted.

Strabismus is common. Strabismus is rare.

The eyes, if injected, have a light red or pinkish color. The blood in the conjunctival vessels is dark.

The pupils are often variable and unequal. The pupils are equal and contracted.

Deafness and blindness are often complete and permanent. Deafness almost always ceases with convalescence. Blindness never follows typhus.

Duration very indefinite, but generally from four to seven days. Duration from twelve to fourteen days.

Relapses are common. Relapses are rare.

The blood is often fibrinous. The blood is never fibrinous.

The lesions, except in the most rapid cases, consist of a plastic or purulent exudation in the meshes of the cerebro-spinal pia mater. In typhus no inflammatory lesions exist.

Mortality from 20 to 75 per cent. Mortality from 8 to 40 per cent.

PROGNOSIS.—In the section relating to the mortality of epidemic meningitis it has been seen that its death-rate varies at different times and places between widely remote extremes. This fact must be borne in mind in estimating the influence of various circumstances in controlling the issue of the disease. The relative as well as the aggregate mortality is far greater in childhood than in adult life. After the age of thirty or thirty-five it decreases rapidly until old age, when recovery from the disease is quite exceptional. A sudden or rapidly developed attack is generally unfavorable, especially when the symptoms are adynamic and there is a purplish discoloration of the skin. Indeed, even apart from evidences of blood-change, cerebral are, on the whole, of graver importance than spinal phenomena, and the more so the more typhoidal their type. Of still more serious significance is a want of perception of the gravity of the situation or unconcern about its issue. A preternaturally slow and compressible pulse implies danger, and so does coolness of the skin, especially if it grows purplish from a diffusion of blood beneath it or even from venous stasis. The various eruptions that have been described including petechiæ, are not necessarily dangerous signs. Profuse sweats during a soporose state, bullæ and gangrenous spots, obstruction of the bronchia with mucus or serum, pneumonia or pericarditis,—these are all grave indications. So, too, are a dry, fissured, shrivelled, and pale tongue or a fuliginous state of the mouth, swelling of the parotids, obstinate vomiting, and profuse diarrhoea at an advanced stage of the disease. Among the most unfavorable nervous symptoms are great restlessness, rigid retraction of the head, spasms of other than the spinal muscles, general convulsions, extensive hyperæsthesia, deep coma, dilatation and insensibility of the pupils or their rapid change from a dilated to a contracted state, retention or incontinence of urine, and all cerebral paralyses, including that of the muscles of deglutition. The favorable indications comprise a general mildness of the symptoms, a moderate loss of strength, a slight degree of pain and muscular stiffness, the absence of petechiæ or vibices (although in many grave epidemics they are of rare occurrence), a desire for food and the ability to digest it. Yet it is imprudent to make an absolute prognosis in any grave case of this disease. Recovery has sometimes occurred when it appeared impossible, and some have died when the period of danger seemed to have passed on the sudden accession of cerebral or spinal nervous symptoms.

TREATMENT.—The difficulties that attend the solution of therapeutical questions regarding diseases which are comparatively regular in their evolution, and are produced by definite causes acting in an intelligible manner, are very numerous and often insuperable. They become multiplied in relation to a disease which, like this one, stands alone in many respects; whose causes, phenomena, and lesions—in a word, whose laws—are specific; and whose varieties of type are as numerous as can be formed by the combination, in a constantly varying proportion, of a special (hypothetical) alteration of the blood, deranging the molecular actions of the economy, and at the same time of an inflammation of the cerebro-spinal meninges, and even of the substance of the great nervous centres. These reasons are sufficient to account for the diverse and often opposite methods of treatment that have been applied to the disease. As in almost all other cases, the methods have consisted in using remedies to counteract certain symptoms—now a stimulant or tonic regimen to combat the debility which conferred the name of "sinking typhus" on the disease; now an antiphlogistic course to allay the inflammation of the brain and spinal marrow denoted by the neuralgic pain and the tetanoid phenomena; and, again, large doses of narcotics to blunt the pain and subdue the spasm. Still other medications have been used with a similar purpose, and some, as we shall see, with more or less theoretical views. It may be said, with Von Ziemssen, "that we are far from having it in our power to decide whether a rational treatment of the symptoms has cured the disease or lessened its mortality;" but a review of the methods that have been employed and their results leads to no doubtful conclusion that some are mischievous and others more or less salutary.

Emetics were among the first medicines used in the treatment of this affection, and were probably suggested by the vomiting which is one of its most constant initial symptoms. But we can readily understand why they failed to afford relief. The vomiting and retching are not gastric symptoms at all, but, as already stated, are due to the irritation of the congestive or inflammatory process at the base of the brain. These medicines may therefore be omitted. The employment of purgatives is even less rational; they debilitate without affording any relief.

Venesection was probably employed as a part of a routine treatment which neither sound reason nor clinical experience justified. It was generally found to fail of its curative purpose, and often induced, especially in young persons, dangerous exhaustion. No better illustration is needed to show that the disease we have been studying is far more than a local inflammation of the cerebro-spinal meninges. On the other hand, local depletion is often of marked utility. Our own experience would lead us to conclude that in the more sthenic cases scarified cups, applied to the nape of the neck and along the cervical vertebræ, are of essential service in mitigating—and generally, indeed, in wholly removing—the neuralgic pains which form so prominent and severe a symptom in many cases of this disease. When any abstraction of blood appears to be contraindicated by the patient's debility, even dry cups will afford him signal relief. Leeches have been applied to the parts mentioned, and over the mastoid processes have sometimes been used with advantage, but their depletory surpasses their revulsive action, and is, so far, injurious. Cold to the head and spine is among the most efficient means of relieving certain symptoms. In the Massachusetts Medical Society's Report of 1810 we read: "Cold water, snow, and ice have been applied to the head when there was violent pain in that part with heat and flushed face, and when there was violent delirium. They afforded great comfort to the patient, and mitigated or removed those important symptoms." It is probable, however, that the value of the remedy is almost entirely restricted to the forming—or at least the early—stage of the attack, when the pain in the head is most intense. Its soothing influence is then very marked, as well as its indirect action in promoting sleep. Heat of head is not an essential condition for its use, for even in the most violent cases it is rarely extreme, and is often entirely wanting. Pain calls more distinctly for the application, and when that symptom has subsided cold is apt to be more annoying than grateful to the patient. Cold is best applied to the head in the form of pounded ice enclosed in a bladder or rubber bag; but cold affusions are also very valuable, especially for children. For the application of cold to the spine the most efficient apparatus is the long, flat rubber bag, either single or double.

From the earliest history of epidemic meningitis in this country blisters formed a conspicuous element in the treatment. They were used, as they had been in other forms of meningitis, to relieve the pain and diminish the congestion in the cerebro-spinal centres. The results of their use were by no means uniform, for not only were they employed in many of the cases which must almost necessarily have been fatal before inflammation could be established, but even in the inflammatory cases they were often applied when time enough had elapsed to allow the exudation to be fully formed, and when, therefore, they were too late to be useful. Again, they were sometimes used so as to vesicate too deeply, and thus by the pain they caused at first, and by the exhaustion that resulted from the excessive discharges they maintained, the patient was more injured than benefited. Our own experience proves that in the early stage of the inflammatory form of the disease blisters applied below the occipital ridge and upon the back of the neck, and only allowed to vesicate superficially, not only remove the pain in the head, but diminish the delirium, spasms, and coma, and therefore contribute as directly as other remedies, if not more so, to the favorable issue of the attack. But such salutary effects are not to be looked for when the disease assumes a malignant type nor after its constitution has become definitely fixed. The application of stimulant and even vesicating agents to the spine below the neck has not been generally practised because, probably, the seat of the spinal lesions was known to be chiefly at the upper part of the organ. Still, the neuralgic pains felt in the spinal nerves may be mitigated by stimulant and anodyne liniments applied with friction to the spinal column.

American physicians early recognized coolness of the skin among the most striking phenomena of the disease; and this probably suggested their use of diaphoretic remedies, among which were the external application of moist heat in baths and warm wrappings, as well as "bottles of hot water or billets of wood heated in boiling water and wrapped in flannel," or the patient "was wrapped in flannel wrung out of boiling water, sinapisms were applied to the feet, while hot infusions were administered, made from the leaves of mint, pennyroyal, and other similar plants, and also wine-whey, wine and water, wine, brandy, and other ardent spirits more or less diluted, camphor, sulphuric ether, and opium. It was not generally thought useful to excite profuse sweating, but important to maintain the activity of the skin from twenty to forty hours, and even longer in some instances. Soup and cordials were at the same time administered. Under this treatment most commonly the violent symptoms, and not very rarely all the appearances of disease, have subsided" (Jackson). Beyond all doubt, this method was a rational one, for it tended to promote an elimination of the morbid poison, while it depleted the blood-vessels and acted revulsively upon the local inflammation of the cerebro-spinal meninges. Yet it seems not to have been revived during the more recent epidemics of the disease, unless, partially, by Gordon (1867), who says: "What I have seen most useful in the stage of collapse is external warmth applied to the entire surface by means of flannel bags containing roasted salt, applied along the spine, along the chest, inside the arms, and to the feet and legs and between them."

Except typhus fever, there is no disease in which a due administration of alcoholic stimulants may become more important. In cases of the inflammatory type they are rarely needful, and are frequently hurtful, but in those which exhibit signs of blood disorder with nervous exhaustion they are often indispensable. Nothing demonstrates their necessity more clearly than the extraordinary tolerance of alcohol exhibited in some cases of the disease. Among the earlier American authorities may be found many illustrations of this statement. Woodward (1808) observed that very large quantities of wine or ardent spirits may be given without injury. Arnell said: "In some cases I have given a quart of brandy in six or eight hours with the happiest effect." Haskell maintained that "the bold and liberal use of diffusible stimuli is the only safe and efficacious mode of treatment." In Ireland the habitual use of alcohol in the treatment of typhus fever no doubt suggested its liberal employment in this disease, but such stimulants have never been in vogue among the physicians of France or Germany. This difference may in part be accounted for by the generally asthenic type of the disease in the first-named country and its more inflammatory character in the others. Similar contrasts of type mark different epidemics, and individual cases during the same epidemic. We have no doubt that while these agents are indispensable in the treatment of cases of the former type, they must even then be exhibited discreetly, for their too lavish exhibition entails the gravest peril by intoxicating the patients and oppressing instead of arousing their vital energies. In 1866, on taking charge of the medical wards in the Philadelphia Hospital, we found that the patients were using as large quantities of alcohol as are given in typhus fever, but a very short period of observation showed that this use of the stimulant was excessive; consequently the dose of it was first reduced, and finally it was omitted altogether unless special indications for it arose. This change was followed by a manifest improvement in the general aspect of the sick and the subsidence of symptoms which, it then became evident, were due to a lavish use of stimulants rather than to the gravity of the disease. Alcohol is no more essential to the treatment of epidemic meningitis than of any other acute affection; it is a cordial to be held in reserve to meet those signs of failure of the heart and nervous system which may arise in all acute diseases attended with changes in the condition of the blood.

The use of opium in the treatment of this disease was strongly advocated by nearly all of the early American writers upon the subject, and by many of them enormous doses were given. It was observed not to produce narcotic effects in ordinary doses. In one case, marked by excruciating pain in the head and maniacal delirium, sixty drops of laudanum were given every hour until nearly half an ounce had been taken within eight hours (Strong). Haskell states: "We have been obliged frequently to exhibit ten grains of opium for a dose in some of the violent cases attended with strong spasms, and have never known it to produce stupor in a single instance." Miner relates that "a few cases imperiously required half an ounce of the tincture of opium in an hour, or half a drachm [of opium] in substance in the course of twelve hours, before the urgent symptoms could be controlled, and even some cases required a drachm in the same time. All these patients recovered." In Europe, Chauffard administered opium in doses of from three to fifteen grains, and Boudin frequently prescribed from seven to fifteen grains at a single dose at the commencement of the attack, and subsequently one or two grains every half hour, until the patient grew sleepy or his symptoms subsided. This tolerance of the drug is remarkable, and so is the fact that it does not cause constipation. These and many similar statements agree entirely with our personal experience. We were in the habit, during the epidemic above referred to, of prescribing one grain of opium every hour in very severe and every two hours in moderately severe cases, and in no instance was narcotism induced, or even an approach to that condition. Under the influence of the medicine the pain and spasm subsided, the skin grew warmer and the pulse fuller, and the entire condition of the patient more hopeful. It seemed probable, however, that the benefit of the opium treatment was most decided in the early stages of the attack, and hence in those in which the inflammatory and spasmodic elements predominated. The hypodermic injection of morphia is to be preferred before the internal administration of other preparations of opium, not only on account of its prompter action, but because it avoids the rejection of the medicine by vomiting. On the whole, Von Ziemssen is within the bounds of truth when he says, "Beyond all doubt morphia may be considered the most indispensable medicine in the treatment of epidemic meningitis."

There is no evidence sufficient to show that epidemic meningitis has ever been cured by quinia alone. In the early prevalence of the disease it was treated by large doses of cinchona, but unavailingly, and subsequently smaller doses were given during the convalescence, as it was in that of other acute diseases. In some parts of this country where miasmatic diseases prevail, and epidemic meningitis, like all other acute, and especially febrile, disorders, displayed more or less of a periodical or paroxysmal type, quinia was used in large doses, but the expected result was not realized. Upham states that in some instances it was given to the extent of sixty, or even eighty, grains within twelve hours from the beginning of the attack, but without effect. In Europe it was extensively tried and unanimously condemned. It may very properly be left out of the list of medicines suitable for this disease, particularly since it is no longer probable that any physician would be rash enough to employ it in the so-called antipyretic doses with or without their usual associates, cold baths. According to Karl Jaffé, the medicinal antipyretics (quinia, salicylic acid, and also sodium benzoate) may be entirely discarded, because they ruin the already weakened digestion.⁵⁹

⁵⁹ Phila. Med. Times, xii. 600.

Common sense has also proved stronger than theory in excluding mercurials from the treatment of epidemic meningitis. At one time they were extensively used, especially when it was learned that the disease in its full development included a paramount inflammatory element. But it was soon found that the results of their use were far from uniform, and farther still from being demonstrably beneficial. In this, as in many other similar cases, it is quite impossible to reach a definite judgment unless it were known what was the type of the cases in which the medicine was given, whether they were asthenic or inflammatory, and again whether it was used during the active or during the declining stage and toward convalescence. In the absence of any trustworthy testimony upon the subject it is only possible at present to state that in the treatment of this disease mercurials should not be used. This conclusion is all the more imperative because the medicine is not an indifferent one. If it is not necessary—and it certainly is not—it is too dangerous in its immediate and ultimate effects for its employment to be warranted.

Since belladonna and ergot were shown to diminish vascular action in the cerebro-spinal axis by contracting its capillary blood-vessels, they have been put forward as having a specific virtue in this disease. If the fact be so, how is that other fact—a clinical one, moreover—to be disposed of, which is that opium, the physiological antagonist of belladonna and ergot, is more efficient than they are in curing the disease? It is possible, indeed, that they may have that curative power, and that opium possesses it also, and that the explanation given of the action of all of these agents is erroneous. Upham states that, in 1863, Haddock recommended ergot upon theoretical grounds, and that during an epidemic at Newbern, N.C., several cases treated by it recovered. Three cases recovered in which it was prescribed by Borland. Read used it in 1873-74 at Boston, Mass., and out of 19 cases 16 recovered and 3 died.⁶⁰ This mortality of about 15 per cent. is not more than half of that which has generally been met with, and if it can be attributed to the treatment would go far to prove the efficacy of the latter. One grain of ergotine, with one-tenth of a grain of extract of belladonna, was administered every three hours. Considering the exiguity of the dose of belladonna, it is not surprising that, except in one case, it did not dilate the pupil; and the dose of ergotine is likewise far smaller than the average medicinal dose of that preparation. Moreover, all of the cases except the fatal ones appear to have presented the disease in a subacute, and certainly not in an aggravated, form.

⁶⁰ Philadelphia Med. and Surg. Reporter, Jan., 1875, p. 68.

In 1872, Dr. S. N. Davis,⁶¹ moved by the success of Calabar bean in tetanus, employed it in this disease. A mixture of one ounce of tincture of Calabar bean with one and a half ounces of fluid extract of ergot was administered in doses of half a teaspoonful every two hours, and with better results than had followed other remedies. Here, again, it is to be noticed that the analogy suggesting the use of physostigma is not a logical one. That drug indeed relieves the spinal spasms of tetanus—a disease in which there is an irritation of the spinal axis, but no exudation from its meningeal vessels, as in the affection we are studying. Moreover, it is a disease of extraordinary power, as shown not only by the spasms, but by the exceptionally high temperature, and thus again is in direct contrast to epidemic meningitis. If, therefore, Calabar bean benefits that disease, it cannot do so in the manner suggested by the author.

⁶¹ Richmond and Louisville Med. Jour., xiii. 711.

Bromide of potassium and hydrate of chloral have also been employed to allay the spasmodic symptoms; but the former is too feeble for the purpose, and the depressing action of the latter upon the heart renders it dangerous. Bromide of potassium has been given to children of two and five years in doses of four and six grains every two hours; but these doses appear to be quite too small even for the purpose in view—viz. to prevent convulsive attacks. Whatever remedies may be suggested hereafter, none should be employed that tend to reduce the power of the heart, which, as we have seen, is dangerously depressed by the disease.

During the decline and convalescence of the affection it is probable that iodide of potassium may be advantageously used to promote the removal of the exudation-matter on the brain and spinal marrow, and probably to prevent the hydrocephalus which sometimes follows the attack, and is attributable to the pressure of effused lymph upon the cerebral veins.

DIET.—The mildly febrile character of epidemic meningitis, and the remarkable debility which characterizes so many cases of the disease, and which, as was before pointed out, conferred upon it the name typhus syncopalis, plainly justify what experience has taught, that appropriate food for the subjects of this affection is at once the most digestible and nutritious that can be taken. It is true that this regimen is interfered with by the vomiting, but, as that symptom is of cerebral and not of gastric origin, it is more apt to be allayed by suitable food than by abstinence. It has been our custom to observe in this disease the same rules respecting diet that are recognized as the most suitable in typhus fever. In doing so, indeed, we did, without at the time knowing it, follow the example of the early American physicians. Strong, who wrote in 1811, advised "soup made from chicken, veal, mutton, and beef, richly seasoned with pepper and savory herbs." These articles were prescribed by him during the height of the disease. Later on he says: "The stomach soon begins to crave something more solid than soup; oysters, beefsteak, cold ham, or neat's tongue are received with peculiar relish. Often I have seen convalescents, when they had hardly strength enough to raise themselves in bed, make a hearty meal of the above-mentioned articles, which were received with great satisfaction, sat well upon the stomach, and were well digested and assimilated." This method is substantially the same that was found successful in the earlier, as it has been in the later, epidemics in this country, and we have no hesitation in attributing to it and the appropriate use of opium and blisters the degree of success we enjoyed in the treatment of the disease in the Philadelphia Hospital and elsewhere.

During convalescence from epidemic meningitis the patient should carefully abstain from physical exertion and mental excitement, and before this state is fully established he should even very cautiously change his position from a recumbent to an erect posture. And, finally, he should return to his ordinary occupations, mental or physical, as late as possible, on account of the danger of a relapse, which has already been described.

PERTUSSIS.

BY JOHN M. KEATING, M.D.

HISTORY.—A careful study of this disease from the various writings since the time of Hippocrates leaves little doubt in the mind of the reader as to its antiquity, so little indeed has it changed in its various characteristics. Whether the affection passed to continental Europe from Africa, or whether its starting-point was India, are questions difficult to solve, and, except for the medical historian, of little import. Desruelles probably truthfully asserts that the many differences which mark the descriptions of the disease, especially by the early Grecian writers, may be due, not to the non-existence of the disease as we know it, but to the influence which climate exerted then as now, and to the unrecognized fact that it is only fatal in its complications. The writings of Hippocrates, Galen, and Avicenna, though undoubtedly referring to the many affections in which paroxysmal cough is a prominent symptom, contain many expressions that would point clearly to the existence of a specific disease. Dr. Watt believed that the disease was not known to the Greeks, and other writers claim that it came from the north and spread southward over Europe about the sixth century; nevertheless, it first appears on record as a distinct affection, disentangled from the confused mass with which it was involved for centuries, about the middle of the seventeenth century. Steffen mentions the first well-established accounts as coming from Baillou in the year 1600, and Schenck in 1650, and Ettmüller in 1685. Sydenham casually mentions it in 1670. Since the time of Willis the definition of the disease has remained unaltered, and so accurate was the description then given of it that we can but naturally conclude that for many centuries at least it has varied but little.

In studying affections of this kind, occurring in epidemic form especially, and which are increased in intensity by whatever means the contagious element, whether gaseous or parasitic, is made more virulent, much allowance is to be made for the climate, customs, and habits of the people whence our data are derived. Thus, most of the diseases of antiquity, the descriptions of which have reached us, have been drawn from types modified by mild climates where the people have led an out-door life, and though the disease we see at the present day is one and the same so far as its causation is concerned, the indoor life and close confinement, the bad ventilation, and the artificial existence in our large cities must weaken the individual, intensify the poison, and exert an influence on the disease.

DEFINITION AND DESCRIPTION.—Whooping cough has been characterized as an acute contagious affection, occurring usually in childhood, though it may occur at any age, and lasting several weeks. It is manifested usually by malaise, catarrh of the respiratory tract, and subsequently by a convulsive cough occurring in paroxysms, the peculiarity of which consists of a series of forcible expirations, followed by a sonorous inspiration or whoop, which may be repeated several times.

At the beginning of these paroxysms of coughing, there are evidences of slight laryngeal irritation, attended by an effort at suppressing the cough; then follow gradually increasing and more audible inspirations, which become more and more difficult. The child is agitated, the face becomes pale, and the countenance has a mingled expression of supplication and fear. If it is old enough it will seize the nearest object for support. As the spell advances, the eyes become suffused and prominent and the loose tissue surrounding the orbits appears puffy and congested. Finally, the paroxysm reaches its height; the child, with a livid countenance, with veins standing out like cords, gives a succession of violent expiratory efforts, followed by a long inspiratory whoop. The same is repeated several times, until finally almost complete cyanosis takes place; the spasm relaxes, a glairy, tenacious mucus runs from the mouth, the contents of the stomach are vomited, and the child falls back exhausted. The lividity of the countenance is succeeded by a deathly pallor; the face still appears swollen and puffy beneath the eyes; the tears course down the cheeks, and frequently hemorrhage occurs from the eyes, nose, ears, or throat, owing to the terrific strain upon the circulation. As soon as the child has recovered from the fatigue of the paroxysm all is apparently over, and were it not for the characteristic expression of the eye, which is pathognomonic in a well-advanced case, nothing would be noticed to even suggest the disease when uncomplicated. The voice is clear; there is little or no elevation of temperature.

The paroxysms which have given the name to this disease can only be likened to an epileptic convulsion, which by gradually increasing cyanosis is self-curable, the carbonized blood finally bringing about an anæsthetic effect. The severity of the paroxysms is by no means in proportion to the local catarrh, which latter may be superficial and slight, not to be detected during life by the most careful laryngeal examinations, and only after death by the aid of the microscope. The frequency and intensity of the paroxysms are dependent in a measure upon the degree of excitability of the nervous system, which of course differs in individuals. It is evident that the success of treatment must be powerfully influenced by this circumstance, and it is partly owing to it that there are so many opinions as to the value of remedies in this disease.

The complications are usually dependent upon outside causes, and have nothing to do with the poison proper of whooping cough, as far as we can tell. There are some which depend on an inflammation of the mucous membrane, which may be limited to any portion of the respiratory tract or may extend throughout it. Complications may arise from mechanical obstruction to inspiration by the swollen mucous membrane or from plugs of tenacious mucus, which may cause pulmonary collapse and favor the development of catarrhal pneumonia, and later even of phthisis; or from impediments to free and easy expiration, whether from spasm of the bronchioles, from forcible compression of the thorax through reflex nervous irritation, or from other obstructions, all of which tend to produce emphysema. Disturbances of the circulation, in the brain or elsewhere, may proceed from thrombi or emboli and give rise to complications which will render fatal an otherwise mild form of the disease. The invariable disturbance of nutrition which accompanies every disease affecting the nervous system is apt to show itself in the breaking down of products which are simply inflammatory. Vomiting may be a most serious complication, both from its immediate and remote effects. It may be due to gastric catarrh, or more frequently to irritation of the pneumogastric nerve.

ETIOLOGY.—Very numerous theories have been advanced as to the nature of this interesting disease. Hufeland, Lebenstein, Pinel, Jahn, Todd, Cullen and a host of others have regarded it as essentially a neurosis. By many others it has been supposed to be due to a lesion of the brain or of its membranes, but careful investigation has established the fact that there is no lesion in whooping cough at all constant or characteristic. By still others, and especially by Gueneau de Mussy, it has been regarded as essentially an affection of the tracheo-bronchial glands, a bronchial adenopathy, causing irritation of the pneumogastrics and of their bronchial branches by pressure of the enlarged glands. We have, however, seen many post-mortem examinations of the bodies of children who have died of measles, where marked enlargement of these glands was constantly found, but where no symptoms of whooping cough had been present. There are indeed many features of the disease which seem inexplicable on any other theory than that the essential cause of whooping cough is a specific poison, and such is the view now generally adopted. This poison is capable of being carried by fomites, though as it is highly infectious it is often communicated through the atmosphere, and is most frequently conveyed from individual to individual. Dolan,¹ who has recently published a very interesting and valuable monograph on this affection, quotes Linnæus, who ascribed it to the irritation of insects, as the author of the modern view that whooping cough is due to the presence of a peculiar microbe, though it must be conceded that as yet it has not been discovered. Most observers hold that the contagium is not in the blood, but that it resides in the secretions of the respiratory passages, and is most virulent during that stage of the disease when the secretion is abundant. Letzerich states that he has succeeded in producing whooping cough in rabbits by inoculating the trachea with the sputa of the human subject. Dolan obtained similar results by injecting the nasal secretions, and also by compelling rabbits to inhale air impregnated with decomposing sputa and vomit of patients suffering with the disease.

¹ Dolan, Thos. M., Whooping Cough, London, 1882.

The following brief statement of his conclusions may be quoted as presenting the most important facts concerning the pathology of the disease:

1st. Pertussis depends on a specific poison or contagion; this is universally admitted.

2d. This contagion is active and highly infectious; this is also granted.

3d. The contagion is analogous to the contagia which produce splenic fever, measles, scarlatina, variola, etc.

4th. It has a peculiar determination to the lungs.

5th. Like all other contagia, it has its period of activity and decline.

6th. The period of greatest activity is in the first and second stages.

7th. Pertussis runs a regular course like measles, scarlatina, variola, etc., and rarely attacks a person but once.

8th. It may thus be classed among zymotic diseases.

9th. The fact that there is no primary pathognomonic morbid change supports this view.

10th. There are various secondary lesions which are characteristic, as ulcerations of the frænum linguæ.

11th. The mode of death harmonizes with this view.

I do not, however, feel entirely satisfied in adopting the view that the contagium of whooping cough resides alone in the mucous membranes of the air-passages.² Children have been known to be born with the disease, the mother having suffered from it some time previous to confinement. The following case occurred under my own observation: Mrs. F——, the mother of two children, was in her eighth month of pregnancy; the two children had at the time a very severe attack of whooping cough, which required the constant attendance of the mother. She, though an extremely intelligent woman, belonged to the poorer classes, and had no one to assist her at this trying time. One day she complained that the movements of her child in utero had entirely changed. Suddenly, without any previous motion, the child would become very active; the force of its movements was such as to make hazardous any attempt on her part to walk in the street. The suddenness with which the movement would come on would oblige her to seize the nearest object for support. This continued until the child was born. Shortly after labor my attention was called to the infant, which had a curious attack, it became deeply cyanosed, seemed asphyxiated, as it were, for a moment, had no convulsions, and within a few seconds resumed its normal breathing and the circulation seemed once more established. I saw the child in several of these attacks; its health did not seem to be impaired, and without treatment, within a few weeks they disappeared altogether. The mother insisted upon the fact that the child had whooping cough, and the absence of the characteristic whoop was the only thing that prevented the diagnosis from being positive. This would show—and there are enough cases on record to warrant our basing an opinion upon them—that the contagium of whooping cough is found not alone in the matters expectorated, notwithstanding the statement of Dolan and others that their experiments failed to show its existence in the blood.

² Colson, Lancet, July 2d.

It must not be forgotten, in reference to cases which seem to have arisen without any exposure to the specific poison, that the characteristic whoop is not always present, and that consequently the true nature of mild cases of the disease which may infect other individuals may have been overlooked. Childhood probably acts as a predisposing cause, though the disease occurs at all periods of life, and as it usually occurs but once in the same individual, it is clear that the apparent diminution of susceptibility in later years may be largely due to the fact that most persons have had the disease in childhood. More children are attacked from one to five years, and the disease is more prevalent in summer and fall months. Causes which, like exposure to inclement weather, give rise to irritation of the bronchial mucous membrane, or diseases which, as measles, are accompanied with catarrhal symptoms and susceptibility of the bronchial mucous membrane, also may serve as predisposing causes. Sex appears to exert some positive influence. Of 360 cases of pertussis by Dessau,³ the total number of males were 154, that of females 206. Girls are more frequently attacked than boys, in proportion of 2 to 1.50; this seems true at all ages; this statement is substantiated by Unruh of Dresden, based on an analysis of 1952 cases.

³ N.Y. Jour. of Obst., 1881, xiv. 490-503.

SYMPTOMS.—The disease begins usually with an ordinary catarrh, preceded by malaise and slight laryngeal irritation, which may be overlooked; in fact, during the first stage there is nothing to attract special attention, unless a direct history of exposure be known and suspicion be aroused on that account. Meigs and Pepper state that the earliest period at which they have known the distinctive whoop of the disease was three days, though in a great many instances it was delayed as late as three weeks. The same authors state that the ordinary duration of a paroxysm or kink is from one-fourth to three-fourths of a minute. They mention a case where the paroxysm lasted fifty-five minutes. Ordinarily they number about thirty-five or forty during the twenty-four hours at the height of the disease, differing greatly in individuals. Their number is most frequent in the course of the third or fourth week, after which they remain stationary, and then gradually decline. The paroxysms may occur spontaneously, or they may follow some irritation, either direct or reflex, or they may be induced by nervous excitement. Toward the end of the attack, after the catarrhal irritation has greatly subsided, or in fact has entirely disappeared, the paroxysmal kinks may be provoked by irritation of the fauces, and also by nervous excitement; and there is no question but that at this time they can be controlled by will-power. In many cases a distinct relapse occurs after the disease has been apparently cured.

Dolan believes the phenomena of the cough or kinks to be due, as suggested by Laennec, to a "spasmodic condition of the muscular or contractile fibres of the bronchi and their branches." He remarks that the lungs are supplied from the anterior and posterior pulmonary plexuses, formed chiefly of branches from the sympathetic and pneumogastrics. The filaments from these accompany the bronchial tubes upon which they are lost. Irritation of these nerves is said to have the effect of producing contractions of the bronchial canals sufficient to expel a certain quantity of air. If this theory is true, it helps us in explaining why the large, mediate, and smaller bronchi are closed during the expiratory stage of the paroxysmal cough of pertussis. The general opinion seems to be that the pneumogastric nerve is not inflamed, as has been asserted by some.

The highly sensitive condition of the nervous system, which is probably in a great measure intensified by the anæmia, and by the interference with nutrition due to the disturbance of the circulation by the cough, will show itself in many ways, and even when no secondary nervous affections complicate the attack or follow it. Some time will elapse after the disease has passed away before the child will recover its self-control, or its nutrition will show the influence of a healthy nervous system. The total duration of the affection is said to vary from six weeks to three months in ordinary cases; though probably, if active treatment could be instituted early enough and kept up with thoroughness, there is no specific disease more capable of being shortened in its course than the one under consideration; this remains, however, for future statistics to decide.

During the second stage of the disease the symptoms are sufficiently marked to attract attention and render a diagnosis easy to make. Frequently the catarrh seems to extend to the bronchioles, and gives rise to symptoms that are alarming; and the intensity of the paroxysm will cause the engorgement of the blood-vessels to get relief in profuse hemorrhage; this is the period for caution. Complications may arise, the strength may fail, the secretions may become too abundant, and asphyxia may ensue; emphysema may show itself, or catarrhal pneumonia may gradually supervene.

The period of decline is very gradual; the secretions become less in quantity and more viscid, the paroxysmal cough is less frequent, but may at times be equally severe, the child's strength is usually exhausted, and its nutrition is greatly impaired. The expected paroxysm throws it into a state of intense nervous excitement; it is sleepless—in fact, worn out. Probably at this period of the disease treatment will show the most marked results, and the long lists of sedatives, tonics, etc. which are presented to us by their zealous advocates owe much of their popularity to their value at this stage of the disease. The catarrhal symptoms are the first to subside; the nervous disturbances remain for some time, and gradually fade, and the constitutional symptoms, or those from exhaustion, are the last to leave the patient.

Strange as it may seem, the heart appears to suffer but little in the long run from the great strain upon it; the palpitation and irregularity of its actions are not followed by structural changes as a rule, though we may state that feebleness of the circulation has remained in most of our bad cases for some months after recovery.

As regards the ulceration of the frænum linguæ, which has given rise to so much discussion as to its exact value as a symptom of this disease, our own experience leads us to believe that though it is nearly always present in the severe cases, its almost invariable absence before dentition and in milder cases shows it to be of traumatic origin. Roger's exhaustive report before the French Academy supported this view, and showed how clearly it is caused by the violent rubbing of the frænum on the free border of the incisors. On the other hand, Delthil of Paris and Blake of England believe that it is a pathological feature of the disease. The former reported cases in which it occurred before dentition. The ulcer is not always found on the frænum linguæ, but is found on either side of it. Bouffier noted severe cases of ulceration in children who had no teeth, but he attributed it to the injury produced by the mother in detaching the mucus with the finger.

Examinations of the urine have been carefully made by many observers. The appearance of sugar, about which so much has been said, does not seem to be constant, or even very frequent. Out of 50 cases, Dolan found traces of it in but 13. This coincides with our experience also, for we have frequently tested the urine in seven cases with negative results. Since, as is well known, irritation of the pneumogastric centre may cause glycosuria, it was at one time attempted to show that the paroxysms in whooping cough were due to congestion of the pneumogastric nerves, a condition which is said to have been occasionally found in this disease. Dolan says he has never seen hemorrhage from the kidneys during the course of whooping cough, nor blood in the urine.

MORTALITY.—It is an extremely difficult matter to reach, with any degree of certainty, the true mortality of this affection. Meigs and Pepper say: "Of the 208 cases observed by ourselves, 143 were simple, all of which recovered;" and, again, "Some form of complication occurred in the 65 of the 208 cases observed by ourselves; of these 65, 12 died." The mortality seems greater under five years; thus: Of the 9008 deaths attributed to it in the United States during the census year ending June 1, 1870, the number of persons under one year of age was 4424, and 8396 were under five years. There were 1784 deaths from it recorded in Philadelphia from 1860 to 1876; of this number, 1724 were under five years of age. The census of the United States for 1880 gives a return of 11,102 deaths from this disease.

Females seem more liable to die of it than males; of the 1784 deaths in this city, 766 were males and 1018 females. As we have already seen, females are more liable to the disease than males.

Robt. J. Lee, M.D.,⁴ says that from the Registrar-General's report of 1876 it is seen that in a total mortality in England of 510,315, whooping cough was returned as the cause of death in 10,554 cases, or nearly 2 per cent.

⁴ In a paper in the British Med. Jour., 1879, vol. i. p. 307.