ter before the attack.* When this phase supervenes, the patient becomes troublesome in an infinity of ways. He lies, steals, bullies his playfellows, resents all control, and seems to delight in attracting attention by putting himself in the way of danger. Such cases are obviously irresponsible and therefore not suitable for punishment; but as they are generally quite beyond the control of their parents and far from welcome in any institution, the problem of their disposal becomes a formidable one. Extreme cases of the refractory type have been grouped under the term of "apache." The history of some of these is so lurid that they have become familiarly known by name and repute to scores of police, public health, parish council and hospital officials. This familiar tendency to perversion or depravity of character is very difficult to explain on any pathological or physical basis. Just as in some forms of late syphilis affecting the main nerve centres the most frequent and distinctive indications are abnormalities of sensation and disturbance of reflex machinery, while in other forms of the same disease early indications are exalted and overweening conceptions and grandiose ambitions and aspirations, so in a fairly common type of late encephalitis it would almost seem as if the virus had a predilection for some imaginary "centre of behaviour" in the brain. Illustrative cases of this nature are described in Appendix II of this chapter. 16. Resemblance or Relation to other Diseases: I. Botulism. -Upon their first appearance in Britain, cases of encephalitis lethargica were thought to be cases of botulism. This malady, due to consumption of food infected with the bacillus botulinus, and encephalitis lethargica have in common certain disturbances of central function and particularly paralyses of certain eye muscles. These resemblances, however, are really superficial. The two diseases have actually no real relationship, as was quickly recognised when encephalitis lethargica became better known in England and Scotland. 17. Resemblance or Relation to other Diseases: II. Influenza. -That cases of mild and sometimes even moderately severe encephalitis lethargica have in innumerable instances been diagnosed as "influenza " is not to be wondered at. The mode of onset of encephalitis is often very misleading and peculiar the practitioner is expected to give an ex cathedra opinion at his first visit; moreover, whether regarded from the clinical, the epidemiological or the bacteriological standpoint, "influenza cannot yet be regarded as a pathological entity, and certainly not as a well-defined disease. Thus it is probably incorrect to say that encephalitis lethargica has been mistaken for influenza. What has happened, and still happens, is that the practitioner Many" of these children "were normal, healthy, active children before their illness: some were scholarship holders, and some are said to have had exceptionally attractive, pleasant dispositions. These children have become irritable, unreliable, deceitful, mean, quarrelsome, spiteful. destructive and lacking in powers of concentration and control. Some of them have become liars and thieves."-Dr. V. Saunders Jacobs. has said "influenza as a vernacular equivalent for "pyrexia of unknown origin." From the epidemiological point of view it has been suggested that there may have been some etiological association between the great epidemic of influenza in 1918-19 and this disease, which appeared among us about the same time, but it is highly probable that this was a mere coincidence. In any case, until "influenza" is more precisely defined and until more is known about it, the question of its possible affinity with other maladies can scarcely be profitably discussed. 18. Resemblance or Relation to other Diseases: III. Poliomyelitis. The disease that is probably nearest in affinity to encephalitis lethargica is poliomyelitis, or the modified form thereof which attacks the brain instead of the spinal cord and is called polioencephalitis. Yet the two diseases are really quite distinct. The lethargy which, if not an invariable feature of encephalitis lethargica, is yet a usual one, is absent in polioencephalitis. The lesions found on post-mortem examination are quite different. Further, while poliomyelitis and polioencephalitis are chiefly, indeed almost entirely, diseases of infancy and early childhood, encephalitis lethargica, while occurring, as we have seen, at all ages, is yet most common in the period 10-20 years. Yet again, encephalitis lethargica is most fatal in the middle period of life, poliomyelitis in childhood and youth. Thus, though these two diseases are alike in affecting the nervous system, in causing paralysis, in being due presumably to a micro-organism, and in manifesting a very low infectivity, they are yet definitely to be regarded as specifically quite distinct. 19. Resemblance or Relation to other Diseases: IV. Herpes Febrilis.-This question perhaps belongs more properly to the etiological or bacteriological paragraph of this chapter. The relation between the micro-organism that is postulated as the cause of encephalitis lethargica and that which causes herpes is still obscure. Between herpes zoster or "shingles," a painful affection which most commonly affects the trunk or the temple, and the herpes febrilis which is usually found on the lips as a symptom or accompaniment of acute pneumonia, it is obvious. that the relation is generic rather than specific. It is with the latter (herpes febrilis) that we are now concerned. The view has been expressed that the virus of herpes febrilis may have existed for an indefinite period in the saliva of man, and that from some cause it gradually or abruptly acquired an increase of pathogenic power. It thus released Von Economo's disease in epidemic form amongst those who could not resist it, and vegetated in the saliva of those who could" (Hall). At present, on the balance of all the evidence, it is unsafe to pass beyond the conviction that the viruses of these two diseases are closely related. 20. Resemblance or Relation to other Diseases: V. Epidemic Hiccough, Paralysis Agitans, Sleeping Sickness and others.About the time when encephalitis lethargica first appeared in England, there were one or more outbreaks of epidemic hiccough. F It now seems probable that the association was no more than accidental; though an etiological relation is not impossible, epidemic hiccough being in that case a modified form of encephalitis lethargica. As was pointed out in paragraph 13 above, there is a close relationship in outward manifestations between paralysis agitans, a somewhat unusual malady of the elderly, and the most familiar form of the late phase of encephalitis lethargica; so close a resemblance, indeed, that the term Parkinsonism, originally applied to the one, has now been transferred to the other. There are many reasons for thinking that the resemblance is apparent only, and that the two diseases are quite distinct. Some, however, noting that the pathological as well as the clinical conditions are somewhat similar in the two diseases, incline to think that there may be some degree of etiological relationship between them. On the whole it seems probable that these two maladies are quite distinct. It is especially significant that the one disease is a malady of advanced life, the other pre-eminently a malady of youth and adolescence. In the popular mind there has been some confusion between sleeping sickness, a disease of native populations in tropical Africa caused by a trypanosome, and encephalitis lethargica, popularly known in this country as sleepy sickness. The confusion is merely one of terminology. The two diseases have nothing in common; although, as it happens, not only the manifestation of progressive lethargy but the nature of the brain lesions is somewhat similar in the two diseases. Encephalitis lethargica is naturally apt to be mistaken for certain other brain diseases with obscure or varying symptoms, especially tubercular meningitis, cerebro-spinal meningitis, and certain tumours and syphilitic affections of the brain. Yet other maladies of which coma or stupor is a feature are apt to be confused with it; such as uræmia, typhoid fever, cerebral hæmorrhage, certain other brain affections such as tumour, and sub-acute disseminated sclerosis. 21. Is Encephalitis Lethargica a New Disease?-In 1917 and 1918, on its first appearance, encephalitis lethargica was regarded as a new disease. That view is probably correct, but there is some doubt on the subject. A Portuguese physician in the sixteenth century described a disease that closely resembles encephalitis. In the seventeenth century in England, in the eighteenth century in France and Germany, and early in the nineteenth century in Italy, epidemics were described in which drowsiness associated with obscure nervous symptoms were the chief manifestations. In the last decade of last century a mysterious malady of similar type, named "Nona," appeared in central Europe. It is well to be extremely cautious in accepting any of these as specifically identical with encephalitis lethargica. On the balance of probability it seems likely that this is a new disease; originated, perhaps, by some harmless or comparatively harmless organism of human parasitic habits, acquiring suddenly an enhanced virulence owing to unknown but readily imaginable reasons. It may be, for example, that the causal organism has been for a long period an innocuous member of the bacterial flora of the human naso-pharynx; and that suddenly as by a "sport or mutation, it either attained an exalted virulence or somehow acquired powers of penetrating the natural defences of its host and so of reaching the cerebral tissues, where it found a soil and a pabulum suited to its need. This suggestion is further considered in the paragraph on infectivity. 22. Pathology and Bacteriology.-Owing to the high casemortality rate in encephalitis lethargica, opportunities for postmortem examination have been only too numerous, and the records of pathological findings are proportionately voluminous. The naked-eye appearances are usually comparatively slight, shewing only moderate congestion of the vessels of the brain, with occasional meningeal hæmorrhages. Microscopically the affected areas shew inflammatory lesions and especially perivascular infiltration and, "later, proliferative processes of a reparative kind" (Marinesco). While the meninges and the white substance may be involved, the grey matter of the brain is chiefly affected, and that most in the neighbourhood of the pons, basal ganglia, midbrain and, most of all, in the region of the nuclei of the cranial nerves. The grey matter in the cord is less prone to be affected. The cerebro-spinal fluid is usually found to be normal. The nerve trunks themselves have occasionally been found to be involved. Beyond the central nervous system no constant or definite lesions have been observed. It has already been said that there is no good reason to doubt that the disease is an infection caused by a micro-organism. Beyond that at the moment it is not possible to go with confidence. Many organisms discovered by various observers have been believed by them to be the cause of the disease. Monkeys (Macacus Rhesus) and subsequently rabbits and other animals have been inoculated with material taken from the brain of dead and the nasal discharge of living human subjects, and have been believed to have acquired the disease, but others have failed to confirm these experimental results, so the matter remains in doubt." It is evident that much further work is necessary before the virus of epidemic encephalitis can be said to have been definitely identified " (Hall, p. 63).' 23. Infectivity.-Even in those areas and periods in which this disease has attained its highest incidence, it has never within the space of one year attacked on an average more than one person in many thousands of the population. Yet even with such an attenuated incidence it is to be expected that now and again and here and there, by the laws of probability, groups of cases will occur in apparent or real association, and so give rise to a suggestion of infection from one another or from a common source. This suggestion may indeed prove to have been well founded; but it is necessary to guard against erroneous inference from what may be a merely fortuitous grouping. But there is more to say there is definite evidence, as in an institutional outbreak at Derby in 1919, that certain series of cases associated closely in time and place were also associated etiologically, and that, accordingly, the element of infectivity, though slight, is not entirely negligible. Against this it has been pointed out that doctors and nurses whose professional duties bring them into close contact with patients suffering from encephalitis lethargica do not seem more prone to attack than the average. It may be that any special proclivity which their duties entail is rectified by the fact that they either work in well-ventilated wards or spend some time in the open air between domiciliary visits. To many the conception of degrees of infectivity is still unfamiliar, and to them a disease is either infectious or it is not. It is clear that the infectivity of encephalitis is not comparable with that of measles or smallpox. The malady is probably rather to be classified in this respect with pneumonia, cerebro-spinal fever and poliomyelitis, in all of which "the pathological agent is much more frequently present in the human organism than the clinical symptoms indicate" (Ministry of Health Memorandum on Encephalitis, 1921). Further knowledge of the precise nature of encephalitis lethargica and the organism which gives rise to it will probably shew that carriers of the disease, harbouring the microbe in the naso-pharynx, are common; that of those exposed to infection only a minute fraction actually acquire it; and that accordingly the factor of a lowered resistance is far more potent than the mere presence or proximity of the infecting agent. Professor Wynne concludes from a review of the facts elicited in connection with the Sheffield outbreak that "there is no good evidence that the disease is spread by direct contact, nor any data for computing an incubation period." Investigation of the cases that occurred in Glasgow in 1923 indicated no suggestion of grouping. No instance of family infection was discovered, every case coming from a separate household. There were in all 397 home contacts of definite cases, but among these there was no evidence of even a mild type of illness. 66 As to the mode and channel of infection, little or nothing is known, but much may plausibly be conjectured. Thus it is probable that there are many carriers" who are either resistant to the virus or whose defences, perhaps partly environmental, have proved adequate; and that these carriers harbour the organisms chiefly in mouth, throat and nose; whence, upon the occurrence of favourable circumstances at which we can as yet only guess, the germs secure entry and reach and find congenial environment in the tissues of the brain. Levaditi and others believe that "the naso-pharynx constitutes for encephalitis as for poliomyelitis the chief, if not the only, source of contagion." Only by invoking the "carrier "hypothesis is it possible to explain the known facts as to the distribution and incidence of encephalitis.. The comparison with acute polio |