Epidemic Encephalitis.

PAUL WATERMAN, M.D., Hartford.

This paper has the sole purpose of indicating the importance which encephalitis has assumed as a clinical problem. Perhaps I can best illustrate this by admitting that I have mistaken encephalitis for influenza, epidemic poliomyelitis, cerebro-spinal syphilis, general paresis, epidemic and tuberculous meningitis, cerebral hæmorrhage and thrombosis, epilepsy, chorea, paralysis agitans, peripheral neuritis from various causes, dementia præcox, manicdepressive psychosis, and brain tumor, to mention cases in which the false diagnosis was actually made and finally corrected, while in other cases the differential diagnosis has been difficult and delayed, and I have no doubt that I have seen other cases of encephalitis in which my error of diagnosis has not been corrected. When I was first offered the opportunity of presenting this subject to you, my first inclination was to decline the privilege because I was at the moment somewhat discouraged by my inability to make prompt and accurate diagnosis when encephalitis was a possibility, but in a moment I realized that my record of mistakes might have their instructive value.

To review briefly the more familiar facts about epidemic. encephalitis, to give a more serviceable and less misleading adjective than "lethargic": the year 1918 brought to us, along with the influenza epidemic, a small number of cases of this disease, which have grown slowly in number and in clinical recognition during the past two years, cases being reported from all parts of the United States. The same development has occurred in Europe since the disease was recognized in Austria in 1917, and other parts of the world have begun to report cases. In its most common symptoms,-somnolence, fever, and ocular paralyses, it had previously been recognized as a syndrome, several epidemics had occurred, and descriptions of it date back several hundred years, but it is only as a result of the more extensive and intensive study of the past two years that it has come to be regarded as a

clinical entity. It is apparently caused by a transmissible and filterable virus, supposed to exist primarily in the upper respiratory passages. Several microorganisms have been described but the specific organism has not yet been confirmed. The pathological process is an inflammatory process in the central nervous system, the cause of which is presumably introduced through the blood vessels, and which consists chiefly in small round cell infiltration, primarily in the neighborhood of the capillaries, with later degeneration or destruction of nerve tissue and with hemorrhages, usually minute, according to the severity of the process. This inflammation is of low grade, does not produce pus or wholesale destruction of nerve tissue, and varies widely both in degree and extent, from a slight diffuse disorder to intense local and general involvement. After a few days or weeks of acute inflammation, the process tends to recede, ultimately leaving more or less permanent scar, according to the degree and character of the acute disturbance of the tissue.

The symptoms and course of the disease vary widely, according to the pathological lesion. It is impractical to describe and unwise to expect any fixed syndrome. While somnolence, fever, and ocular palsies have been mentioned as the most characteristic symptoms, many cases occur in which no two of these symptoms appear and some cases in which no one of them is noted. To form a clinical picture of the disease it is best to think of the various symptoms that would be produced singly or in combination by the varying pathological process. In the first place there tends to be a respiratory, less often a gastro-intestinal infection, followed by a hematogenous infection, of low grade, and this in turn by evidence of disorder in the central nervous system. This latter disorder tends to involve a large area of the brain with the result that all the cerebral functions are more or less impeded, but the more significant clinical feature is the tendency toward a maximum involvement of some anatomically distinct area of the system or of several areas simultaneously or in succession. For clinical interpretation it helps, I think, to distinguish the following anatomical areas, according to the functional disorders manifested: meninges, with meningitic or pressure symptoms; cere

bral cortex, with paretic, irritative, and epileptic symptoms; subcortical area, with disorders of association, chiefly psychic; pyramidal tract, hemiplegic types; basal nuclei, thalamus and corpus striatum, chiefly higher coordination and correlation disorders of muscle tone and movement, such as hypertonus, athetosis, chorea, paralysis agitans, and catalepsy; medulla, with cranial nerve palsies of nuclear type and vagus disorders; spinal cord, with disorders of the anterior horns, posterior ganglia, or of the whole section of the cord; and the peripheral nerves, with irritative and paretic sensory and motor disorders.

As a result of this variable anatomical localization, numerous clinical types have been described, as determined by the dominant functional disorder, such as the meningitic, lethargic, cataleptic, epileptic, delirious, acute psychotic, paralysis agitans, choreic, polioencephalitic, and anterior and posterior poliomyelitic types.

Neurological diagnosis in general can often do no more on preliminary or first examination than to determine the existence of a certain anatomico-functional disorder. In some cases it is clear that the given disorder must be a part of a certain disease process, while in many other cases the given disorder might be a part of any one of several different disease processes, the correct determination of the actual process being made by the course of the symptoms, by the successive elimination of some of the possibilities and by the accumulation of symptoms positively indicative of a certain single disease process.

This diagnostic difficulty applies particularly in epidemic encephalitis, because in this disease we have not as yet any single pathognomic symptom. When somnolence is marked, and especially when it is associated with transient or prolonged ocular palsies of nuclear type or even with a history of transient diplopia, in a youth or young adult in the winter half of the year, without evidence of tumor or meningitis, the immediate diagnosis of encephalitis is fairly justified. But sometimes marked meningitic symptoms are present with many small white cells in the spinal fluid, or pressure symptoms with rapidly progressive choked disc and vomiting appear with history of slow onset and of many weeks' duration, and then the diagnosis is delayed. Sometimes the

early picture is that of an extensive anterior poliomyelitis or of a transverse myelitis, in which case the further course of the disease may and usually does provide the differential diagnosis. Rarely the late picture is that of dementia præcox of catatonic type without history of acute onset or illness, or a typical picture of paralysis agitans. Two of this latter type I hope to show to-day, in one of which I had no definite data of the onset, while in the other case I made a positive diagnosis of epidemic encephalitis when I first saw the patient in the first week of the disease. Without this early observation all that one can do in this type is to state that there exists a lesion of the corpora striata, probably the result of an acute infectious inflammatory process and therefore probably epidemic encephalitis.

Sometimes there is a positive Wassermann or other signs of syphilis, sometimes history or evidence of intracranial injury, sometimes some other general infection is present, sometimes quasi-hysterical symptoms confuse the picture. In one case the onset followed a severe electric shock, was succeeded by sleeplessness and marked restlessness that appeared to be largely neurotic, and in turn by a severe streptococcus sore throat, with a history of brief moments of double vision during the early period. of restlessness; the electric shock was promptly eliminated as a cause of the total condition, but the streptococcus infection, present from the onset, delayed the positive diagnosis of epidemic encephalitis until the streptococcus infection was removed, while the apparent neurotic factor prevented my giving full weight to the history of diplopia, especially since there was no medical observation of ocular paresis.

I have said that the original designation "lethargic" is misleading, as is the common name of "sleeping sickness," and it is true that if one awaits the appearance of somnolence many cases will pass unrecognized, for sleeplessness and irritability are not uncommon, sometimes marking the onset for several days, to be followed by somnolence, sometimes following an initial somnolence, sometimes alternating with it more or less irregularly. I think that the most confusing cases are those occurring in older persons in the pre-senile and senile period, when the symptoms on first and even second observation are such as might be

caused by arterial sclerosis of the cord, bulb, or brain, unless perhaps it is the very mild cases that must occur not infrequently and that are liable to be regarded as respiratory infections or influenza and which do not come to hospital or neurological observation. Cases may undoubtedly be surprisingly limited in their clinical manifestations, as in one which complained solely of vertigo, apparently of the auditory type, there being probably affection of the cochlear nuclei on one side.

The spinal fluid has not yet given us much positive assistance in diagnosis, although it assists by exclusion of a few diseases. It is clear, with pressure increased slightly or not at all, very rarely in any considerable degree, sometimes without white cells, more often with 6 to 20, very rarely over 100, with slight if any change in globulin content, and according to some recent findings, with increased sugar content.

None of the somatic symptoms is specific, although their combination or succession is usually strongly suggestive. The cranial palsies are of nuclear type and most commonly of the third or sixth ocular nerves, less often of the seventh, and the third nerve paralysis shows its nuclear origin usually in the involvement of separate nuclei rather than of the whole third nucleus group. When the ocular palsy is the dominant symptom, as it often is, associated with little or even no symptom of involvement of the hemispheres, it tends to persist for several days or weeks, whereas when it is rapidly followed by more marked encephalitic symptoms it commonly disappears in a day or two. It is of greatest service to watch the abdominal reflexes, as a most sensitive sign of diffuse cerebral disorder, while a more specific involvement of the motor pathway gives increased deep reflexes and the Babinski group of reflex signs.

While the course of the active disease process may be brief or prolonged, a few days or several weeks, the convalescence, even of the lightest cases, is surprisingly prolonged, dominated by cerebral fatigue, both mental and physical, and by cerebral irritability if the fatigue warning is not heeded.

Treatment has, of course, no positive procedures of curative value, but disregard of its few indications may aggravate the course unnecessarily. Physical and mental rest and quiet are