THE LIBRARY OF THE UNIVERSITY OF CALIFORNIA LOS ANGELES EPIDEMIC ENCEPHALITIS [encephalitis lethargica] $3.50 EPIDEMIC ENCEPHALITIS [encephalitis lethargica] BY FREDERICK TILNEY, M.D., Ph.D. Professor of Neurology, Columbia University; Attending Neurologist, the Presbyterian Hospital and the New York Neurological Institute; Consulting Neurologist, Roosevelt Hospital, New York AND HUBERT S. HOWE, A.M., M.D. Instructor in Neurology, Columbia University, Assistant Visiting Neurologist, the Presbyterian Hospital, New York NEW YORK PAUL B. HOEBER 1920 Copyright, 1920 By PAUL B. HOEBER Pul^lished June, 1920 Prinicd in the Unilcd States of America BNoedical FOREWORD Epidemic encephalitis has engaged attention so exten- sively throughout this country for the past two years that its clinical, pathological and etiological features are now matters of general medical importance. Its con- currence with influenza emphasizes this importance and raises new questions in an ali'eady perplexing epidemic problem. Numerous studies of this form of disease have appeared in many periodicals. Perhaps it is opportune at the present time, however, to assemble the results of clinical studies upon selected groups of cases in the form of a small brochure. This book contains observations made on two separate groups of cases which seem to cover most of the recog- nized clinical forms in which encephalitis may occur. The first group, reported l^y Drs. Frederick Tilney and Henry Alsop Riley, appears as Part I; the second, by Dr. Hubert S. Howe, as Part II. The point of view relative to each group is essentially similar concerning the main features of the disease. Such minor discrepancies in detail as may be apparent are dependent upon the variabihty of the symptom- complex rather than upon differences of interpretation. Epidemic encephalitis is now so well estabhshed as a chnical entity that the lessons learned from it shed con- siderable light upon acute diseases of the brain which formerly occasioned much perplexity in diagnosis. The groups of cases comprised in the following records illus- trate the protean nature of this acute inflammatory re- V VI FOREWORD action in the tissues of the central nervous system. It is probable that in the final analysis the symptom-com- plex will be considered as due to a general infection in- volving the system as a whole, but expressing itself most cogently as an encephalomyelitis. CONTENTS PART I CHAPTER I Page INTRODUCTION AND CLASSIFICATION 3 Nomenclature — Chief Characteristics — Division of Epi- demic Encephalitis into Recognizable Clinical Types. CHAPTER II LETHARGIC TYPE 5 Profound Somnolence, sometimes unaccompanied by but often with Cranial Nerve Palsies — Extreme Asthenia. Case I — History — Neurological Examination — Cranial Nerves — Fatal Termination — Post-mortem Report on Brain. Case II — Temperature — Mental Depression — Festination. Case III — Somnolence — ^ Rigidity — Dip- lopia — ^Laboratory Findings — Complete Recovery. Case IV — Somnolence with Occasional Low Delirium — Neurological Examination — Ptosis — Mental Inertia. CHAPTER III CAT.\LEPTIC TYPE 20 Case V — History — Neurological Examination — ^Labor- atory Tests — Fatal Termination. Case VI — Connection with Influenza — Neurological Examination — Long Dura- tion of Illness. CHAPTER IV PARALYSIS AGITANS TYPE 27 Presence of Symptoms of Parkinsonian Syndrome — Agi- tans Tremor. Case VII — Symptomatology — Neurolog- ical Examination — Cranial Nerves — Rapid Fatal Termi- nation. Case VIII — Symptoms — Neurological Examina- tion — Tremor — Death due to Intercurrent Operation. Case IX — Original Mistaken Diagnosis — Presence of Vlll CONTENTS Pack Tremor in Limbs and Extremities — Neurological Examina- tion — Recovery. Case X — Parkinsonian Symptoms with Tremor — Neurological Examination — Cranial Nerves- Mental Disturbances — General Improvement. Case XI — Loss of Motor Activity — Neurological Examination — Absence of Tremor — Cranial Nerves. Summary of Dis- tinctive Features of Five Foregoing Cases. CHAPTER V POLIOENCEPHALITIC TYPE 41 Symptoms Related to Polioencephalitis, with Frequent Paralysis of Oculomotor (third) nerve — Absence of Leth- argy. Case XII — Symptoms, Bilaterial Facial Paralysis — Asthenia — Neurological Examination — Gradual Re- covery. Case XIII — Delirium — Paralysis of Oculo- motor Nerves — Asthenia — Recovery. Characteristics of this Type — Abortive Form of the Disease— No History of Influenza. CHAPTER VI ACUTE ANTERIOR POLIOMYELITIC TYPE 45 Case XIV — Diagnosis of Infantile Paralysis — Prolonged Somnolence (six weeks) and Lower Motor Neuron Type of Paralysis, Indicating Involvement of both Brain and Spinal Cord. CHAPTER VII POSTERIOR POLIOMYELITIC TYPE 47 Inflammatory Affection of Dorsal Root Ganglia. Case XV — Double Vision — Herpetic Eruption — Lethargy — Zoster-like Involvements. CHAPTER VIII EPILEPTO-MANIACAI. AND ACUTE PSYCHOTIC TYPES 50 Case XVI — Hallucinosis and Delusions — Maniacal Man- ifestations Alternating with Coma — Fatal Termination. Case XVII — Bronchopneumonia Symptoms — Apathy, Lethargy, Occasional Acute Psychosis. CONTENTS IX CHAPTER IX Paoe INFANTILE TYPE (NEONATORUM) 54 Manifested when only a Few Weeks Old. Case XVIII — Sleep Lasting Two Weeks Followed by Paralysis of Left Side of Face. Case XIX — Three Weeks of Somnol- ence with Left Facial Paralysis. Case XX — Two Weeks of Somnolence with Paralysis. CHAPTER X DISCUSSION M Critical Analysis of Symptoms and Course of the Disease in Cases Presented — Onset — Lethargy — Cranial Nerve Palsies — Temperature — Tremor — Asthenia — Restlessness — Catalepsj' — Spinal Fluid. Course and Duration. CHAPTER XI PROGNOSIS AND DIAGNOSIS 63 Prognosis Varies with Type — Guarded Prognosis Ad- visable especially in Early Stage — Still Further Tj'pes Recognizable — Differential Diagnosis — Groups Recog- nized by Spinal Fluid Test — By Pathological Tests — By Chnical Tests. CHAPTER XII NATURE OF THE DISEASE 68 Early Forms — Communicability — Agent not Differen- tiated — Relation to Acute Anterior Poliomj^elitis — To Influenza. CHAPTER XIII TREATMENT 73 Moderate Isolation — Principle of Treatment Sympto- matic — Elimination — Feeding — Lumbar puncture — Car- diac Stimulants — Narcotics — Rest ('ure During Conval- escence — Massage for Facial Palsy — Galvanic Sinusoidal Current. X CONTENTS PART II CHAPTER XIV ETIOLOGICAL FACTORS AND CLASSIFICATION. .69 Age — Sex — Relation to Influenza — To Poliomyelitis — Method of Transmission. Classification of Anatomical Types. General Outline of Various Forms — Meningitic — Cortical — Pyramidal System — Thalamic — Corpus Stri- atum — Brain Stem — Cerebellar — Spinal — Per i p li e r a 1 Nerve — Multiple Diffuse Lesion. CHAPTER XV PATHOLOGICAL CHANGES 85 Macroscopic — Microscopic — Mesodermogenic and Ecto- dermogenic Tissue Changes. CHAPTER XVI SYMPTOMATOLOGY 92 Constitutional Disturbances Followed in 2-14 Days by Somnolence or Other Characteristic Symptoms — Sensory Disturbances — Mental Symptoms — Fever — Ocular Symptoms. Blood Examination. Spinal Fluid. PROGNOSIS -..••, 107 CHAPTER XVII CASE REPORT I 113 History and Symptoms — Physical, Neurological and Laboratory Examinations — Slow Onset (4 Months) — Weakness — Dizziness — Drowsiness — Ocular and Mental Changes — Rapid Recovery. CHAPTER XVIII CASE REPORT II 122 Onset with Head-cold, Headache, Fever, Slight Delirium Followed by Stupor, Rigidity and Double Ptosis — Death on 42d Day from Respiratory Paralysis. • CONTENTS XI CHAPTER XIX Page CASE REPORT III 129 General Weakness — Blurring of Vision — Apathy — Insom- nia — Complete Recovery in 7 Weeks. CHAPTER XX CASE REPORT IV 137 Presents Typical Parkinsonian Syndrome — Also Uncon- trolled Smiling — Left Facial Weakness — Mental Changes — No Improvement. CHAPTER XXI CASE REPORT V 149 Drowsiness — Double Ptosis — Rigidity of Jaw and Neck. Death From Respiratory Paralysis. Autopsy — Microscopical Examination. CHAPTER XXII CASE REPORT VI 164 Weakness — Lethargy — Involuntary Movements of Head and Legs — Severe Constipation. Partial Recovery after 5 Months. CHAPTER XXIII CASE REPORT VII 179 Onset Followed Influenza — Temperature — Weakness — Difficulty in Speech and Swallowing — Ataxia of Lower Extremities — Gradual Improvement. CHAPTER XXIV CASE REPORT VIII 188 Influenza 10 Months Previous — Headache — Blurred Vision — Difficulty with Hearing and Speech — Somno- lence. Partial Recovery Leaving Hemilateral Paralysis Agitans and Paralysis of Right Face and Tongue. CHAPTER XXV CASE REPORT IX 199 Onset with Obstipation, Fever, Delirium Followed by DifEoulfcy in Walking and Speech, Symptoms Lasting Nearly 2 Years. XU CONTENTS CHAPTER XXVI Page CASE REPORT X 210 Choreo-athetoid Movements of Left Arm, Head and Left Side of Face. Gradual Onset — Stupor^Delirium — Choreo-athetoid Movements of Left Arm, and Left Side of Face. Left Pto.^is. Duration 3^ Months- Very Gradual Improvement. CHAPTER XXVII CASE REPORT XI 231 Characteristic Stupor — Clinical Evidence of Lesions of Brain Stem and Spinal Cord — Duration 2 Weeks — Fatal Termination — Axitopsy. CHAPTER XXVIII CONCLUSIONS 248 BIBLIOGRAPHY 252 ILLUSTRATIONS Page Oculomotor Nucleus 10 Hemorrhage in Medulla 11 Hypoglossal Nucleus 12 Vascular Infiltration 13 Hemorrhage in the Thalamus 14 Abducens Nucleus 14 Thalamus. Diffuse Cellular Infiltration 86 Thalamus. Cloudy Swelling of Neurocytes 87 Thalamus. Acute Cloudy Swelling of Nerve Cells. . . 88 Thalamus. Higher Magnification. Severe Degenera- tive Changes and Neuronophagy in Some of the Nerve Cells 89 Capillary Congestion in Internal Capsule Bordering on Thalamus 90 Internal Capsule. Capillary Congestion and Char- acter of Invading Cells 93 Accumulation of Ameboid Glia Cells in the Internal Capsule 95 Internal Capsule. Diffuse Cellular Infiltration. 97 Internal Capsule Showing Adventitial Lymph Space Infiltration 99 Internal Capsule, Showing Adventitial Lymph Space Infiltration 100 Medulla. Hemorrhage, Infiltration and Vascidar Changes in Substantia Reticularis Grisea 102 Medulla. Localized Cellular Infiltration of Formatio Reticularis Grisea 103 Medulla. Diffuse Infiltration 105 Medulla. Acute Cloudy Swelling in the Cells of the Nucleus Ambiguus lOG Medulla. Formatio Reticularis Grisea 107 Cortical White Matter. Occipital Lobe. Localized Accumulations of Ameboid Neuroglia Cells 108 Fig. 23. Cliromatolysis and Acute Cloudy Swelling in tlie Cells of the Anterior Horns of the Spinal Cord ... 110 xiii Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. Fig. 9. Fig. 10. Fig. 11. Fig. 12. Fig. 13. Fig. 14. Fig. 15. Fig. 16. Fig. 17. Fig. 18. Fig. 19. Fig. 20. Fig. 21. Fig. 22. XIV ILLUSTRATIONS Page Fig. 24. Blood Vessel Showing Virchow-Robin Space Packed with Lymphocytes Ill Fig. 25. Case II. Temperature and Pulse Chart During Final Week of Illness 127 Fig. 26. Case III 131 Fig. 27. Case lY. Stiff, Slightly Flexed, Statuesque Attitude, with Tendency to Fall Backwards 145 Fia. 28. Case IV. Parkinsonian Facies, Attitude and Tremor of Right Hand 145 Fig. 29. Case IV. Uncontrollable Smihng and Weakness of Left Side of Face 147 Fig. 30. Case V 151 Fig. 31. Case V 153 Fig. 32. Case V. Temperature and Pulse Chart During Final Week of Illness 157 Fig. 33. Case VI. Series of Photographs Showing the Various Phases of Movement continually present. No. 1 . . 165 Fig. 34. Case VI. No. 2 166 Fig. 35. Case VI. No. 3 167 Fig. 36. Case VI. No. 4 168 Fig. 37. Case VI. No. 5 169 Fig. 38. Case VI. Composite Photograph with Five Expo- sures on One Plate Showing Movement of Head.. 170 Fig. 39. Case VI. Standing Attitude 171 Fig. 40. Case VIII. Weakness of Right Half of Tongue 191 Fig. 41. Case VIII. Mask-like Face and Characteristic Posi- tion of Arm 192 Fig. 42. Case IX. Standing Attitude; Showing Slight Tremor of Legs 204 Fig. 43. Case IX. Showing Mask-like Expression of Face . . . 206 Fig. 44. Case IX. Showing Facial Weakness on Attempting to Smile 207 Fig. 45. Case X. A Series of Photographs Illustrating the Progressive Phases of Movement and Facial Ex- pression through which the Patient is Constantly Passing. No. 1 212 Fig. 46. Case X. No. 2 212 Fig. 47. Case X. No. 3 213 Fig. 48. Case X. No. 4 213 Fig. 49. Case X. No. 5 214 ILLUSTRATIONS XV Pack Fig. 50. Case X. No. 6 215 Fig. 51. Case X. No. 7 216 Fig. 52. Case X. No. 8 217 Fig. 53. Case X. General Position Usually Assumed. Head Thrown Back and Inclined to the Left. Left Arm Flexed and Left Hand Closed. Permanent Dorsal Flexion of the Toes on the Right Side... 21S Fig. 54. Case XI. General Appearance. Constant State of Lethargj'- 235 Fig. 55. Case XI. Shaded Area — Hypaesthesia, Hypalgesia Thermohypaesthcsia 236 Chart I. Cataleptic Tj-pe. Facing page 23. Chart II. Paralysis Agitans Type. Facing page 28. Chart III. Acute Psj'diotic Type. Facing Page 53. PART I CLINICAL TYPES OF EPIDEMIC ENCEPHALITIS A Preliminary Consideration of Some of its Prominent Clinical and Patholooical Mani- festations. EPIDEMIC ENCEPHALITIS CHAPTER I INTRODUCTION AND CLASSIFICATION The epidemic appearance of an unusual disease which affects the nervous system profoundly has, during the past year, been the subject of much interest and in- quiry both in England and in this country. From the fact that its most conspicuous clinical feature is prolonged somnolence it has acquired, in the lay prints, the perhaps not unjustified, if somewhat confusing, designation of "Sleeping Sickness." Economo^^ devised the term "Encephalitis Lethargica" in describing a similar epidemic in Vienna during 1917; but as Kinnier Wilson^^ has pointed out, this nomencla- ture is inaccurate, since it is the patient who is lethargic and not the encephalitis; so that to label it "Epi- demic Encephalitis" is less open to criticism if not as picturesque. The chief characteristics of the disease are that: 1. It tends to appear in epidemic form. 2. It produces prolonged somnolence or a state closelj' resembling lethargy. 3. It gives rise to palsies of the cranial nerves. 4. It causes a marked asthenia. 5. It is pathologically based upon an acute encephalitis. Its pathogenesis is a little understood and much debated question. 3 4 EPIDEMIC ENCEPHAIJTIS From the very nature of the lesion, an inflammation of the brain, it might be predicted that there would be a multiformity in the cerebral symptoms. The remarkable fact is that the clinical picture presents such distinct generic definition in spite of the specific variations to which it is subject. It is especially to these variations, or subgroups of the disease, that attention is here directed not only as a matter of classification but also as an oppor- tunity to discuss the significance of the disease in some of its relations to certain aspects of cerebral physiology. Of twenty cases of epidemic encephalitis which have come under the observation of the authors, eight fairly well-defined subgroups or clinical types have been rec- ognized, as follows: 1. The lethargic type. 2. The cataleptic type. 3. The paralysis agitans type. 4. The polioencephalitic type. 5. The anterior poliomyelitic type. 6. The posterior poliomyelitic type. 7. The epilepto-maniacal type. 8. The acute psychotic type. Each subgroup is described because of some distinctive feature in its development and course. It would almost seem advisable to include in this list another type, the recognition of which depends rather upon the extremely early age of incidence than upon any particular clinical feature. At all events, the occurrence of the disease in infants during the first month of life is perhaps a striking enough character to justify a tentative group in the new- born, encephalitis neonatorum. CHAPTER II LETHARGIC TYPE In this type of epidemic encephalitis the predominant clinical feature is the lethargy or profound somnolence which the patient manifests. This condition can hardly be described as a coma or stupor, since it is possible to arouse the patient momentarily out of the deep sleep into which he has fallen, to gain his intelHgent coopera- tion for a brief period in which there is evidence of little or no mental clouding, after which interval he lapses into deep sleep again. In not a few such cases the lethargy continues for a number of da3^s, even until the patient dies, without apparent further involvement. In most instances, however, the lethargy is complicated by the appearance of cranial nerve palsies, most commonly paralysis of the oculomotor group, while in those cases which make a more or less complete recovery, an extreme asthenia develops early and is a persistent symptom. The first case illustrative of the lethargic type is se- lected as an especially good instance of this variety of the disease, and also because it has been possible to study the entire brain stem in complete serial sections. Case I. Mrs. de la C, married, age thirty-six, whose previous personal and family history had little bearing upon her final illness. Four weeks prior to the on- set of the disease she suffered from what had been re- garded as an influenza bronchitis. She was not seriously 5 6 EPIDEMIC ENCEPHALITIS ill at any time during this affection and made what ap- peared to be a complete and satisfactory recovery. One morning after an apparently good night's rest, she failed to rise at her usual hour, and in fact, showed no inclina- tion to do so. This at once attracted the attention of her family, since she had always been an energetic and effi- cient housekeeper. It was found, however, that in spite of all efforts to arouse her, she would fall asleep again after opening her eyes for a few seconds and responding intelligently to questions asked her, without seeming to realize anything except that she was very tired and wanted to sleep. In the brief periods in which she was awake and conversed with the family her replies to questions indicated that she was suffering no pain and was not con- scious of any distress. When seen by her physician she was still in the same deep sleep, breathing regularly and with normal heart action. The temperature taken by mouth showed no elevation. This somnolence continued for two days interrupted only by brief periods during which she was sufficiently aroused to take small quan- tities of food and fluid, both of which were swallowed in a normal manner. Her almost trance-like condition aroused the suspicion in her physician's mind that the patient was suffering from hysteria, and upon this basis he sought some explanation in the more recent occur- rences of her life. It developed that there had been some slight misunderstanding between the patient and her husband, but upon careful investigation this proved to be nothing more than many other similar and customary differences which had occurred in the past. After two more days of increasing somnolence, the theory of hys- teria was finally abandoned and the patient was seen by a neurologist. At this time it was still possible to arouse the patient for an instant or so, but immediately she CLINICAL AND PATHOLOGICAL MANIFESTATIONS 7 would lapse back into a profound and quiet sleep. When asked to open her eyes, she attempted to comply, but was unable to elevate the lids, in spite of the fact that she clearly understood the request to do so. Swallowing had become difficult and unless fluids were carefully given, would cause paroxysms of coughing and some regurgi- tation of the fluid through the nose. When requested to protrude the tongue, the patient, although appearing to understand what was said, was unable to move the tongue in any direction. On several occasions she at- tempted to speak but her voice sounds were feeble, husky and indistinct. When her lids were elevated by the ex- aminer, there appeared to be a slight double external strabismus and a widely dilated pupil which did not react to light upon either side. The pulse and respiration were normal and the temperature by rectum was 101 degrees. The remainder of her neurological examination showed that all of the deep reflexes were present, including the jaw, pectoral, biceps, triceps, radius, ulnar, wrist, patellar and Achilles, and equal on the two sides. Of the super- ficial reflexes, the upper and lower lateral abdominals were present and equal, right and left. There was no Babinski, Chaddock, Oppenheim, Gordon or Schaefer. No abnormal involuntary movements, such as tremors, twitchings or spasms, were observed in any part of the body, nor were they observed or reported at any time during the disease. No estimate could be made of the muscle strength, although the patient was able to and did move all four extremities and occasionally turned from one side to the other. The electrical reactions were not taken. Myotatic irritability was normal. It was impossible to obtain anj'' satisfactory estimate of general somesthetic sensibility, because of lack of 8 EPIDEMIC ENCEPHALITIS cooperation on the part of the patient. It did appear, however, that she had perception, especially of the pin- point and tubes containing hot water. She showed evi- dent displeasure when stimulated in this way or by over extension of the fingers and toes. Concerning the cranial nerves, no conclusion could be drawn with reference to the special senses, although she seemed to see when the eyelids were opened and understand what was said to her. The eyegrounds were normal; the pupils were widely dilated but did not react to light, either directly or consensually. The drooping of both lids was evidently due to a definite ptosis, and the existence of a slight degree of double external strabismus has already been noted. There was no nystagmus or other involuntary eye movements. In the later stages of the disease the jaw muscles seemed to have become paralyzed, as the lower jaw dropped and the mouth gaped widely. There was distinct weakness of both sides of the face, while the difficulty in deglutition and phonation, together with a paralysis of the tongue, have already been mentioned. At the end of the fourth day of her illness she was trans- ferred to the hospital for further investigation. Her temperature had risen to 103° by rectum, her respiration was shallow, and her heart action weak. The systolic blood pressure registered 100 mm. Hg. Examinations of the blood and spinal fluid were en- tirely negative; the spinal fluid showed no increase in cells and no globulin, and was negative to the Wasser- mann test. Deglutition became increasingly difficult, so that it was necessary to feed and stimulate by rectum. During her second day in the hospital, respiration grew progressively more shallow and seemetl to ])e interfered with by some CLINICAL AND PATHOLOGICAL MANIFESTATIONS 9 obstruction in the upper respiratory passages. It ap- peared advisable to make a laryngoscopic examination in order if possible to determine the point of obstruction. This examination revealed a bilateral total paralysis of the vocal cords. Several hours after the laryngoscopic examination, respiration ceased and finally after a few gasping attempts to breathe, the patient died of respii-a- tory paralysis. POST-MORTEM REPORT ON THE BRAIN The Meninges. The dura mater covering the convexity of the brain and also upon the base was normal in its appearance. The pia mater, however, especially that covering the basal surface, showed a considerable degree of injection, while upon the convexit}' nothing considered pathological was noted. Surfaces. All surfaces of the brain were normal in appearance, there being no evidence of hemorrhage, softening or atrophy. Macrotomic Sections. Sections of the brain in the gross showed nothing pathological in the cerebral or cerebellar hemispheres. The entire brain stem was intensely injected and had a pinkish appearance sugges- tive of recent inflammatory reaction. This was particu- larly true of the medulla oblongata, the midbrain and the thalamus. Microtomic Sections. Upon microscopic examination the pia mater covering the medulla oblongata showed considerable injection and there was a moderate degree of round cell infiltration, not, however, comparable to the condition seen in lethal cases of acute anterior polio- myelitis. Two of the cranial nerve nuclei, the nucleus hypoglossi and nucleus ambiguus, were specially inves- tigated; both of these areas showed distincl ('clluhu' 10 EPIDEMIC ENCEPHALITIS changes and nearly all of the cells in both nuclei appeared to be pathological. These alterations varied from a mod- erate degree of cloudy swelling with eccentric nucleus and obscurations of the Nissl bodies to a fairly ad- vanced chromatolysis in which the more central layers of tigroid bodies had disappeared. A slight degree of neuronophagia was manifest, especially in the hypo- FiG. 1. — Oculomotor Nucleus. glossal nucleus. Ameboid glia cells could be observed collected around many of the motor cells of the nucleus which were in a more advanced stage of degenerative change. The blood vessels in the medulla oblongata presented an interesting picture; both veins and arteries were much engorged, • but the hyperemia was more pronounced upon the venous than on the arterial side. Numerous CLINICAL AND PATHOLOGICAL MANIFESTATIONS 11 small hemorrhagic areas were observed, especially around the smaller veins, and a fairly well defined cellular infiltra- tion was found in the adventitial lymph spaces which contained accumulations of leucocytes and plasma cells. A slight degree of gliosis was discernible in and about the nucleus of the hypoglossal and vagus nerves. Pons Varolii. This portion of the brain stem also showed a slight degree of infiltration in the pia mater. Fk;. 2. — Heiuorrlui^i m AkUalla. The nucleus abducentis was especially studied, and here, as in the case of the medulla, the large motor cells showed evidence of acute change, varying from intense cloudy swelling to a moderate degree of chro- matolysis. In a few instances, the cell bodies showed vacuolization. The vascular picture was similar to that observed in the medulla and was characterized by numer- 12 EPIDEMIC ENCEPHALITIS ous small hemorrhages apparently in relation to the veins, all of which were intensely injected. The teg- mental portion of the pons presented a slight degree of gliosis, but this could not be made out with certainty in the basal portion. Midbrain. More pronounced, perhaps, in this region than in any other portion of the brain stem were the • * r*.'". '.■ * *A -^ ^■^*v -— ^■'> =j^ftt: Fig. 3.— Hypoglossal Nucleus. changes already described. Not only did the motor cells in the third nerve nucleus and the cells in the red nucleus show such changes as cloudy swelling and chromatolysis with a moderate degree of neuronophagia and vacuoliza- tion, but the hemorrhagic areas were more numerous, and in many places the vessels showed thrombosis with a tendency to necrotic change in the adjacent tissues. This was particularly true of the region of the midbrain CLINICAL AND PATHOLOGICAL MANIFESTATIONS 13 immediatel}' about the substantia nigra. Similar hemor- rhagic and throm])otic changes were observed in the thalamus, hj-pothalamus and corpus striatum. A summar}^ of the pathological alterations observed in this case justified the diagnosis of acute polioen- cephalitis. The nuclear changes in the medulla explained the paralj^sis of the tongue and the final failure of cardiac Fig. 4. — Vascular Infiltration. and respiratory action. In the same manner the altera- tions in the midbrain about the nucleus oculomotorius furnished the cause for the oculomotor palsy, while there is some ground for the belief that the changes in the thalamus and about the aqueduct of Sylvius may \>e held responsible for the prolonged and deep somnolence. The pathological changes in this case are shown in Figs. 1-6. 14 EPIDEMIC ENCEPHALITIS W::'r:-*y^f^'^^^j^^^ ?»,V ■■■'•-. - ' ■■•-■■■' , ''iS Fig. 5. — Hemorrhage in the Thalamus. Fig. 6. — Abducens Nucleus. CLINICAL AND PATHOLOGICAL MANIFESTATIONS 15 Case II. The second case of the lethargic type of the disease is that of a physician forty-three years of age who suffered from influenza in November of 1918. After recovery from this infection, he was busily engaged in practice until March 2, 1919. Much of his time was given to caring for patients suffering from influenza during the severe epidemic of this disease which pre- vailed in New York during the winter. On March 2, 1919, he developed a temperature of 104° which continued for one day, and varied for the next three weeks between 100° and 102°. During the first part of this period he was restless and unable to sleep and then he began to yawn and become very drowsy, sleeping most of the time; he would even fall asleep when conversing with his friends or physician. His expression became glassy and fixed. He could be aroused to take nourishment for a few moments and although he seemed oriented and in complete contact with his environment, his entire atti- tude at these times was one of indifference and apathy. He remained in bed for three weeks until the fever dis- appeared and following this was confined to the house for another week. Mentally he was very much depressed, but in addition to a marked degree of salivation, showed little in consequence of his recent illness. Upon advice, he took a trip to the mountains which seemed to do him little good; the depression and salivation still remained and the tendency to yawn returned. He noticed an oily secretion from his forehead, and his skin would show a red tache on even the slightest stimulation. There was an unnatural flush over each malar prominence and his face had a glassy and fixed expression. Upon return- ing to practice he noticed that he was troubled with much nervous unrest, a feeling of disquiet in his legs. This made it necessary for him to move his feet about constantly whenever he sat down. This sense of disquiet 16 EPIDEMIC ENCEPHALITIS was further augmented by the development of a pecuhar contraction of the muscles of the big toe on the right foot, which occurred spasmodically many times a day whether he was walking or at rest. Ijatterly he has com- plained of a slight tendency towards festination, so that while the case may be considered as representative of the lethargic type, it seems to tend in its late consequences towards some of the features of the Parkinsonian syn- drome, especially the wax-mask, the disquietude in the legs, and the tendency towards propulsion. Case III. P. E., Presbyterian Hospital, No. 40,374. Male, fifty-two years of age, driver by occupation. On January 1, 1919, the patient developed a fever, became markedly irrational and complained of severe, constant headache. His history showed no previous illness, either recent or remote. He had not suffered from influenza. After a period of marked restlessness and insomnia lasting three days after admission into the hospital, he gradually became more and more somnolent and re- mained in a stage of lethargy for three weeks. During this time he could be aroused and for a moment or two would respond to questions and follow simple instruc- tions. He took his food well and would even sit up in bed if instructed to do so. Immediately after being aroused, however, he would lapse back into a somnolent condition, in which he would remain almost without a movement of his limbs for a number of hours. Both arms and legs were held in a semiflexed position most of the time, but it was possible to extend them without much force, the muscles seeming to be in a slight degree of spasticity. All the deep reflexes were active and equal on the two sides. There was no clonus and no Babinski or any other pathological reflex observed. On January 14, 1919, the right pupil was larger than the left and was fixed CLINICAL AND PATHOLOGICAL MANIFESTATIONS 17 to light stimulation. There was also a right divergent stra- bismus but the fundoscopie examination showed nothing abnormal in either eye. Upon testing the vision, it was found that there was a diplopia on looking both to the right and to the left. This was considered indicative of a partial paralysis of the third nerve'on the right side. The following laboratory records are significant: January 2, 1919. Spinal fluid, 5 c.c. withdrawn, slightly tinged with blood. There was no increase of pressure. The fluid contained 23 lymphocytes and 5 polymorphonuclear cells. No organism was detected in the smear; the culture of the fluid was negative, as was also the Wassermann reaction. Blood culture on the same date was sterile; the stools showed no blood, bacillus typhosis or bacillus dysenteriae. The blood Wassermann test was negative and the blood count showed white blood cells 12,700; polymorpho- nuclear cells 83 per cent. Januarj^ 10, 1919. Blood count normal. X-ray of the skull negative. January 11, 1919. Spinal fluid, 15 c.c. of clear fluid obtained under no increase of pressure. Cell count showed 12 l3'mphocytes and 1 polymorphonuclear cell. Globulin was negative, culture was sterile, Wassermann test negative. A guinea pig injected with the fluid obtained from the lumbar puncture remained normal. Subsequent Wassermann tests upon the blood and spinal fluid, as well as blood counts and chemical inves- tigation of the blood, revealed nothing pathological. The patient remained in this stuporous condition until the 1st of February, 1919, but at this time was fairly rational when questioned, although he occasionally attempted to get out of bed. 18 EPIDEMIC ENCEPHALITIS On February 3d the patient became more acute men- tally and was quite rational. His somnolence had almost entirely disappeared; he sat up in bed and ate with apparent enjoyment. During the following week he gave the impression of a man suffering from some mental impairment without fever or other indication of acute illness. He had so far recovered by February 14, 1919, that it seemed advisable to discharge him from the hospi- tal. Ultimately he made a complete recovery. Case IV. J. B., age fifty-nine years; a butcher. In the fall of 1918, the patient suffered from a rather severe attack of influenza from which he made a fair recovery. In the early part of December, however, he suddenly became ill again while carrying on his day's work. He complained of pain in the head and great fatigue which made it impossible for him to remain at his business. He came home and went to bed. In a short time he fell into a deep sleep and with the exception of an occasional low muttering delirium remained in this condition for the following four weeks. His temperature at the onset was 102.5°, at which level it remained with very few and slight exacerbations during the remainder of his illness. At the end of two weeks, his continued lethargy alarmed his family and several consultations were requested. At this time, neurological examination showed that all of the reflexes were normal although slightly more active in the lower extremities than in the arms. They were equal upon the two sides and no pathological re- flexes were observed. The tone of the muscles throughout the body was slightly increased, but there was no stiffness of the neck. The patient remained immobile in one po- sition for hours at a time; his breathing was normal and regular; his pulse and blood pressure good. The sensory examination was rendered impossible because of lack CLINICAL AND PATHOLOGICAL MANIFESTATIONS 10 of sustained cooperation on the part of the patient. He could be aroused from his lethargy sufficiently to answer a question intelligently and then would lapse into sleep again or perhaps into a low muttering delirium. The cranial nerves showed a slight degree of ptosis in both ej'es; both pupils were widely dilated and reacted but sluggishly to light, with a slight external strabismus of the left eye. The blood and spinal fluid were negative to all laboratory tests. At the end of four weeks, he began to emerge from his lethargy and manifest interest in his surroundings. He has not, however, within the past four months, recovered sufficiently to return to his business. In fact his mind seems to be blank and he sits, most of the time, in an apathetic and indifferent attitude, considerably disor- iented and without initiative. His oculomotor palsies have entirely disappeared. This case is illustrative of the lethargic type of the disease in which the cerebral cortex appears to have suffered severe injury, as evidenced by the slow psychic improvement in the patient. The characteristic clinical features in this lethargic group of cases is the pronounced lethargy which was common to them all, together with an elevation of tem- perature. Three of the four patients had previously suf- fered from influenza within a relatively short time of the onset of the encephalitis. In three of the ca.ses, cranial nerve involvement causing oculomotor and bulbar palsies occurred. Only one of the cases terminated fatally and that after a rapid course of six days' duration. Of the patients who recovered, one showed no ill effects of the disease, one had a prolonged asthenia, and the third is giving some evidence of a tendency' in the direction of a Parkinsonian syndrome. CHAPTER III CATALEPTIC TYPE The two cases of this group . present a striking sim- ilarity. Both were young girls, one eleven years of age, the other sixteen years old. Case V. R. Z., female, sixteen years, operative. The patient was previously a healthy, robust girl who, upon returning from work December 9, 1918, complained of a severe pain in the index finger of the right hand which came on during the afternoon. Later in the evening the pain spread to her right arm, where it persisted for several hours only to disappear as suddenly as it had come, and leaving behind it a slight paralysis. At this time she sud- denly became irrational in her actions. For a short time she was quite violent, even requiring restraint and seda- tive treatment. Her family believed she had ''gone in- sane." Subsequently she became quieter and fell into a deep sleep. Her temperature showed a slight elevation of 102° with a corresponding quickening of pulse and respiration. She continued to sleep the following day and never from that time throughout the remainder of her illness, which lasted eight weeks, did she again open her eyes. For some days she lay in this lethargic condi- tion, able to move her body from side to side and having some voluntary control of her muscles. At the end of the first week of her illness, she mainfested a general rigidity in her entire body which, however, was peculiar in the fact that the limbs could be easily moved from one posi- 20 CLINICAL AND PATHOLOGICAL MANIFESTATIONS 21 tion into another. There was no stiffness of the neck or other evidence of meningeal involvement. Although seeming to be in deep sleep, the patient gave evidence of hearing and understanding all that was said to her when aroused. She was unable to make any ade- quate response in reply to questions or directions. If asked to protrude her tongue she would make a feeble effort to do so. When told to flex the forearm upon the arm, she made evident attempts in this direction but seemed unable to carry out any voluntary act. Both eye- lids remained closed and all her own efforts to elevate them were unavailing. Neurological examination at this time showed the patient lying supine in bed, eyes and mouth closed, forearms slightly flexed on arms, the latter being adduc- ted, fingers partially flexed, legs flexed on thighs, the thighs slightly flexed upon the pelvis. This attitude gave her the appearance of "an eflftgy on tomb" as Hall'^ has described this appearance. She made no movements; her deep reflexes were pres- ent and active on the two sides but there was no apparent pathological change in them. The superficial reflexes were present and active on the two sides. There was no Babinski or any modification of this reflex. The muscle tone was markedly increased, showing a pronounced, inflexible rigidity. The muscle tissue itself was firm and tense but showed no disposition toward cramping. The patient was unable to cooperate, hence all sensory tests were omitted. There was no response to tests for the sense of smell, sight or hearing, and for this reason it is impossible to form judgment concerning the special sensory status. The drooping of both upper lids already referretl to was due in part, at least, to an oculomotor 22 EPIDEMIC ENCEPHALITIS ptosis, but the impression was also conveyed that there was a certain increased rigidity in the orbicularis palpebrarum muscles which tended to hold the eyelids closed. The eyegrounds were normal. Both pupils were widely dilated and failed to react to light. There was slight external strabismus of the left eye. The masticatory muscles held the jaws partially closed. There was no facial palsy, but the facial muscles seemed stiff and fixed, giving the patient an unchanging expression. The winking reflex was absent. The glosso-pharyngeal, vagus and spinal accessory nerves gave no evidence of pathological involvement, although at times the patient had some difficulty in swallowing. In general appearance the tongue was normal and there seemed to be no hypoglossal involvement. In so far as might be judged from the limited cooperation on the part of the patient, the mental status was normal. When aroused, she heard and understood what she heard, and on several occasions showed that she was keenly alive to the purport of conversation carried on about her. This was particularly evidenced when the remark was inadvertently made in her hearing that she was very ill and would probably not recover. Immediately tears began to stream down her cheeks, a reaction which could not be regarded as purely coincidental. Her family history was negative except for epilepsy in an older sister and a partial hemiplegia in her father which has already cleared up. The neurological examination showed that there was no true paralysis, since the patient could make faint indications of movements in all parts, her efforts being very slow and of limited excursion. She was unable to raise her head from the pillow and seemed to have no CLINICAL AND PATHOLOGICAL MANIFESTATIONS 23 power in the back muscles. When any movement was attempted, a coarse tremor developed, which had a moderate intensity and began in the extremities whence it spread to the rest of the musculature. Repeated examinations of the reflexes failed to disclose anything that was considered pathological in this regard and the apparent paralysis was considered as due to the increased muscle tone rather than to any direct pyramidal tract involvement. Of the cranial nerves, the oculomotor group, including the third, fourth and sixth nerves, showed a right ptosis and the right pupil somewhat smaller than the left. The trigeminus was apparently normal in both its sensory and motor divisions. Laboratory Tests. The blood and spinal fluid were investigated several times. In each instance the blood proved negative, both in its count and general mor- phology. The Wassermann was negative, as was also the blood culture. The spinal fluid was clear and showed no increase in pressure. It contained three lymphocytes, no globulin and the Wassermann reaction was negative. At no time did the urine show any pathological changes. The patient's mental condition remained unchanged. Gradually her stupor became more profound until it was impossible to arouse her. This change was attended by a gradual tendency to increased temperature accom- panied by an elevation of the pulse which fluctuated between 120 and 130 for some days before death. The temperature is shown in Chart I. After an illness of forty- seven days the patient passed into a terminal coma and died. No autopsy was obtained. Case VI. J. B., age eleven, school girl. This girl had always been a healthy and bright child until December, 24 EPIDEMIC ENCEPHALITIS 1918, when she suffered from a severe attack of influenza. At the same time her mother and two other sisters had this disease. The mother and one of the sisters died of it, but the patient made a complete and rapid recovery. She returned to boarding school in the early part of January. On January 30, 1919, she was seized with what was considered a nervous chill, followed by a rise of temperature, sleeplessness and a coarse, choreiform type of twitching which manifested itself in all the muscles of the body. Three days later she became stuporous and passed into what was considered to be a coma. Upon admittance to the hospital, her position in bed was described as that of "an image," for she did not move her limbs; her eyes remained closed and it seemed impossible for her to express her wishes by any sign whatsoever. Although in this seeming deep lethargy it was apparent to those about her that she understood most of what was transpiring, for when instructed to squeeze the doctor's hand when she meant to answer "yes," she would on several occasions make feeble pressure in this way. The neurological examination showed a patient, lying in bed upon her back, eyes closed and cheeks flushed, breathing quietly, with arms, legs and the rest of her body held rigidly in a fixed position. The muscular status showed a marked hypertonus which made passive flexion and extension quite difficult. If placed in a given position, the arm or leg would remain as placed without any attempt on the part of the patient to change it. There was a slight carpoptosis with moderate flexion of all fingers of both hands, as well as a pedoptosis with a tendency for the toes to be held in plantar flexion. The reflexes, however, were all normally active and equal on the two sides. The threshold of both patellar CLINICAL AND PATHOLOGICAL MANIFESTATIONS 25 reflexes was twelve ounces, which may be regarded as up to normal standard. There was no clonus at the ankle or patella, neither was there a Babinski nor any confirmatory sign of the same. The conclusion drawn from the reflex status of the patient was that, although she was markedly hypertonic in her muscles, this was not due to a pyramidal tract lesion, but should be regarded as a defect in the extra- pyramidal system. When passively elevated, both arms would show a coarse oscillation or tremor and the same was true of the lower extremities. Upon passively opening the mouth, a coarse tremor was noted in the tongue. There were no abnormal, involuntary acts reported or observed and no abnormal associated movements could be elicited. Tests for somesthetic sensibility were unavailing, since the patient could not cooperate in the examination. The cranial nerves accessible to approach, showed a bilateral slight degree of ptosis and some rigidity in the orbicularis palpebrarum muscle. The third, fourth and sixth nerves could not be properly tested, as the patient seemed unable to move her eyes in any direction. A slight degree of external strabismus was noted in the left eye. Both pupils were widely dilated and reacted but sluggishly to light. The muscles of the lower jaw manifested a certain degree of tension but presented no paralysis. The right side of the face seemed somewhat flatter than the left. Deglutition was difficult and phona- tion impossible. The patient could not protrude her tongue or move it in any direction. There was no stiffness of the neck muscles, such as occurs in meningitis, but there appeared to be no power to move the head in any direction. Examination of the blood and spinal fluid was negative 26 EPIDEMIC ENCEPHALITIS on repeated tests. The blood count was normal and the blood culture sterile. Spinal fluid was withdrawn under a slight increase of tension and contained seven lympho- cytes, no globulin and gave a negative Wassermann reaction. On several occasions, the urine showed a slight amount of pus but this promptly cleared up on proper treatment. In other respects, the urinalysis showed nothing pathological. The patient has remained in this rigid, lethargic condi- tion for three months. During this period the tempera- ture averaged 102°. Once it became subnormal, and on the thirteenth day of the disease it suddenly rose to 106°, on the twenty-second and twenty-third days respectively, to 105° and 104.5°, and on the thirtieth day, to 107.1°. Each elevation was followed by a sharp fall in the curve toward the normal line. The respiration and pulse did not tend to vary pan po.ssw with the temperature; particularly was this true of the pulse, which showed a marked variability throughout the entire course of the disease. The child is still alive and said to be improving slightly. She seems to have regained some power of expression and is able to smile faintly or indicate that she understands the questions addressed to her by gentle pressure of her hand. These two cases are presented as typical of the catalep- tic variety of the disease. One of them had previously suffered from influenza, while in the other no such history is obtainable. They are so strikingly alike in their principal clinical features as to justify the recognition of the cataleptic type of epidemic encephalitis. CHAPTER IV PARALYSIS AGITANS TYPE To this subgroup belong a number of cases charac- terized by the development of several of the more important sj'mptoms of the Parkinsonian s3'ndrome. Case VII. The patient, Mr. A. A., showed his first symptoms on January 21, 1919. At that time he com- plained of some headache, chillv sensations, and a nasal discharge. He felt ill but denied being nervous or de- pressed. His face and body were covered with perspira- tion at frequent intervals. His temperature was 100.2°. He had a few mucous rales in his lungs. On one examina- tion his deep reflexes were exaggerated, and there was some muscular rigidity which had not been recognized by the patient. The diagnosis of influenza was made, and the patient received the influenza vaccine, remaining in bed until February 3d. At this time a lumbar puncture was made, 38 c.c. of fluid being withdrawn under greatlj-- increased pressure. The Wassermann test of the fluid was negative, as was also the examination for tubercle bacilli. There were six cells in the fluid and the Noguchi test was negative; the sugar reduction was normal. On February 3d the patient became drowsy, arousing at times and occasionallj' getting out of bed. It was noticed that his extremities were stiff and trembling, especially on the right side, and the facial expression was fixed while the eyelids were kept closed. He gave the impression of great lassitude and lack of interest in his surroundings. 27 28 EPIDEMIC ENCEPHALITIS Especially during the night there was a great deal of restlessness, which was not allayed by bromides given in considerable quantities. During the first two weeks in February, the patient at times was out of bed and saw a few friends, but he seemed incapable of any sustained interest. The stiffness of the right arm and hand increased materially. The lassitude continued and on several occasions there was retention of urine. This condition of affairs continued until February 21st, when the patient evidenced less and less interest in his surroundings and the restlessness increased at night to a low muttering delirium. During the latter part of February, the patient became much quieter, sleeping soundly most of the time but talking and muttering while asleep. Profuse sweating continued to appear over the head and limbs, while the tremor of the upper and lower extremities on the right side became more pronounced. On February 28th the patient lapsed into a state of unconsciousness with in- continence of urine. The pulse became much weaker and the respiration shallow and hurried. On March 1st he passed into coma and died on March 2d. The temperature was, in general, low, varying from 99° to 100.4° with occasional elevations to 102° and 103°, until February 23d, when it began gradually to ascend and continued to do so progressively to the end, the final temperature being 106.2°. The pulse varied between 98 and 110 until February 23d, when it also ascended uAtil February 27th, then becoming so variable in force that an accurate count could not be made. The respiratory rate remained constantly around 24 until the 24th of February, when it began to increase rapidly. A record of the pulse, temperature and respiration is shown in Chart II. A distinct cerebral tache developed after the fourth week of the patient's illness and during the fifth and sixth ;r5 7^/ 1;^/^ s- ?^ liP. M. A. M. P.M. A.M. P. M. A.M. F ' s- U t ^ /^ "/ ^ /; 9 ^ /? -^ ^ / ^ V It ^ : '- '- : 1 E E z : -: I I E : \ E \ '- : : \ i '- : : E r I : : : \ ) : ^ E E ^ : : : : ''^ : \ E : ^ [ ^ ^ ; ': : E z t : E t E i - = :" i : \ i z j \ ^ j : : : L." :' ;^ ^Y A \ \ ^ • ^ ^ •s z ^r 1 i i- z : ■s. > :*- .^/ /: z \ y ^ : \ i : ^ '^ \-, I = : E .X •r, ,^ t -•.^ y' ^ i- <: V- V'-^.. »: = :.. -f- : ~i' \;.* i \' ^-. : : : I z - - - - - . 1 : : : I ! E E E E : E E : CHART II. PARALYSIS ACITANS TV'PE CLINICAL AND PATHOLOGICAL MANIFESTATIONS 29 weeks there was a marked rash over the abdomen. The entire duration of the disease was forty days. Several repeated examinations of the blood and spinal fluid failed to reveal anything pathological. The neurological examination of this patient made in the third week of his disease showed a man of middle age, lying supine in bed with eyes closed and responding indifferently to questions. His face had a definite wax- mask expression and in the right arm and leg there was a tremor which was continuous during rest, fairly large in its amplitude and relatively slow, resembling in all respects the tremor of paralysis agitans and having the further characteristic feature in the fact that it dis- appeared when the patient moved arm or leg. All of the normal automatic association movements of the face and eye, of eye muscles and neck muscles, of the intra- segmental movements of the arm and the intersegmental movements of the arm and leg were suppressed. It was possible to arouse him sufficiently to make tests of his gait and station. While he was rising from the lied the complete suppression of the normal automatic associated movements, especially upon the right side, was observed. In standing he had a typical Parkinsonian attitude and his gait presented a marked festination. When ques- tioned, he complained of a feeling that made him fear that he might pitch forward when walking or standing and he vouchsafed the information that he felt that he could run better than he could walk. His whole attitude and appearance were unmistakably those of a Parkin- sonian syndrome, more pronounced upon the right side of the body. On returning to bed, he immediately lapsed into a somnolent state from which he could be readily aroused sufficiently to cooperate with intelligence. The reflexes of both upper and lower extremities were present 30 EPIDEMIC ENCEPHALITIS and active, being slightly more active upon the right than the left side. There was no Babinski or other patho- logical reflex observed at any time during the course of his disease. The abdominal reflexes were present as were also the ciliospinals on both sides. The muscle tone in the right arm and leg was distinctly increased as compared to that upon the left side. Beside the tremor at rest, there were no other irregular, involuntary acts recorded. The tests for somesthetic sensibility, in so far as the patient was able to cooperate, showed no departure from the normal, all qualities and modes of sensibility being intact. Cranial Nerves. The patient was able to recognize several different aromatics in either nostril. His vision was 20/20 in each eye without correction; the perimetric fields were impossible of definition on account of lack of cooperation; the pupillary reactions and the fundi were normal; a slight degree of nystagmus was present at times; there was no strabismus and no ptosis. With the exceptions mentioned, the third, fourth and sixth cranial nerves were normal. The trigeminus nerve showed no disturbance in its motor or sensory divisions. In the facial nerve, no definite paralysis was observed, although attention has already been called to the im- mobility of the face, giving rise to a typical wax-mask appearance. The ninth, tenth, eleventh and twelfth nerves were all normal. There was, however, some distinct monotony in the voice such as is usual in cases of paralysis agitans. This case of epidemic encephalitis has its chief interest perhaps in the fact that it presented the paralysis agitans type, rapidly running a fatal course. CLINICAL AND PATHOLOGICAL MANIFESTATIONS 31 Case VIII. Mrs. W. B., forty-nine years of age, an active and robust woman who, in October, 1918, suf- fered from a severe attack of influenza and pneumonia particularly affecting the right lung. This condition kept her in bed for several weeks, and her convalescence was slow, so that she was not in a normal condition again until the beginning of December, 1918. For several weeks she went about as usual seeming to enjoy good health; but about the middle of December she was stricken again with an acute attack giving rise to fever, headache and general malaise. The exact nature of this disorder was not at the time clearly understood. Her temperature did not at any time exceed 103°, but continued for several weeks. Even after the temperature had ceased, however, she did not seem to regain her health; she suffered from a marked asthenia, not merely of physical strength but in initiative as well. Several days after the fever had left her she awakened one night to find herself in a profuse perspiration and her right arm shaking somewhat violently; and this tremor in the right arm and hand continued without cessation or much modification until the time of her death. She was unable to sleep during the remainder of the night, and upon arising in the morning noticed that a similar tremor was present in the right leg and foot. She was conscious that all her movements, particularly on the right side, had become annoyingly and perceptibly slower and that everything she did was, in her own words, ''greatly slowed down." At the end of a week, her whole appear- ance and attitude had changed; the tremor was not the only feature of her trouble which annoyed her; for she felt a stiffening of the muscles in her arm and leg, to- gether with a great sense of disquietude throughout her entire body. When she attempted to walk, she found that 32 EPIDfeMIC ENCEPHALITIS her gait was shuffling and slow. She herself made the observation that her speech had a mournful monotony about it for which she could not account. Upon neurological examination at this time, she pre- sented a typical Parkinsonian attitude in standing as well as lying down. There was a tremor at rest in the right upper and lower extremities with marked hyper- tension in all of the muscles of the body. All automatic associated movements in the face and eye muscles, in the neck and arm muscles, in the arms and legs, were either abolished or distinctl}^ decreased in their activity. The gait was shuffling, with some festination and a subjective sense of procursion. The patient stated that she felt she could run better than she could walk. One very striking feature of the case was the marked sense of disquiet and a desire to move the limbs from place to place but finding no position in which they were quite comfortable. Every position assumed very quickly lost the little relief which it originally afforded, so that the patient was in a state of constant mental and physical unrest which preyed upon her night and day, disturbed her sleep and harassed her when awake. The deep reflexes of the right arm and leg were some- what more active than the corresponding reflexes upon the left side. The abdominal reflexes were absent, due probably to the fact that the abdomen was greatly dis- tended b}^ a large cystic fibroid of the uterus. There was no Babinski on either side and no pathological reflex of any kind. The blood and urine examinations were negative. The spinal fluid was not examined. At the end of two months, it became necessary to interfere surgically for a pelvic condition which seemed to jeopardize the patient's life. In consequence, a laparo- tomy was performed, the operation being a short one, CLINICAL AND PATHOLOGICAL MANIFESTATIONS 33 lasting only one hour, gas, ether and oxygen being the anesthetics. The patient, however, never regained con- sciousness and died in thirty-six hours. This case was the subject of several consultations and much difference of opinion. B}^ some it was con- sidered as a purely functional disorder, having the character of a hysterical tremor. This supposition was substantiated by the fact that the patient, prior to her illness, had been engaged in war work among soldiers returning from France, many of whom were suffering from "shell-shock." Ultimately, however, the clinical features of the disease were too definite to leave room for doubt in the matter of its close correspondence to a typical Parkinsonian syndrome. The case is remarkable for the rapid development of its paralysis agitans features as well as for the absence of any conspicuous period of lethargy or somnolence. Case IX, Mr. B., forty-two years of age, married, merchant. The course of the disease in this patient stands out in pronounced contrast to the two cases already cited. Although a definite Parkinsonian syndrome developed, its full evolution was slow and its course short, the patient making a complete recovery. During the summer, Mr. B. had complained of some intestinal disturbance, was predisposed to lassitude and some disinclination to participate in his usual occupation and amusements. In the early part of December, it was discovered that he was suffering from a tapeworm. Other than this, his previous history contained nothing of particular note, as he had always been a man who enjoyed good health and was unusually active. He did not suffer from influenza so far as he and his family can recall. 3 34 EPIDEMIC ENCEPHALITIS In January, he went to a sanitarium to take vermi- fugic treatment, which proved successful in all respects. Several days after this treatment, instead of feeling improved, he complained that he was no better; in fact, he thought he felt much worse than before. He showed no disposition to get up and be about but preferred to remain in an inert if not semistuporous condition most of the time. He had no particular restlessness nor did he show any mental disturbance, but his conduct was marked by an unusual indifference to his surroundings. After remaining for one week in this condition, he began to see double, while his ph3'^sician noted that there was a slight palsy of the right side of the face. His indifference increased; he seemed to have lost all initiative and noth- ing succeeded in gaining or holding his attention. He was neither stuporous nor comatose; when addressed he would respond in a listless manner. He could be aroused and made to get out of bed. Upon such occasions his physician noticed that the attitude of his body, the position of his arms and head, the expres- sion in his face, and his movements in walking were strikingly similar to the appearances of paralysis agitans without the tremor. The patient was seen in consultation and the diagnosis of brain tumor was made. At the end of four weeks, however, there appeared in the left foot a tremor typical of paralysis agitans. This slowly extended in the course of the next few days until it involved the entire left leg and finally manifested itself to a slight degree in the left hand and forearm. Neurological examination at this time showed a patient with a characteristic wax-mask expression, in addition to which there was a shght facial palsy upon the right side and an oc'casion;d diplopia due undoubtedly CLINICAL AND PATHOLOGICAL MANIFESTATIONS 35 to a weakness of the right oculomotor nerve. There was a slight degree of ptosis of both eyelids. The tremor in the left foot and leg was unquestionably of the agitans type, not only in its rate and amplitude, but also because it occurred during rest and disappeared during action. The reflexes on the two sides were active and equal. There were no pathological reflexes observed, either deep or superficial, although there was a slight tendency toward increase in tone of the muscles upon the left side. The patient had some festination in the gait and complained of a sense of procursion. Sensibility was normal in all qualities, and the special senses, with the exceptions already noted, were intact. The patient continued to be apathetic and generally somnolent for several weeks, but by degrees these symptoms disappeared, and at the end of two months not only the tremor and stiffness of the muscles but the Parkinsonian attitude and expression had entirely disappeared. This patient did not have fever at any time during his disease His urine and spinal fluid were negative. Eventually he made what is considered a complete recovery and is now in a state of health which he himself beheves to be normal. Case X Miss H. M. H., thirty-eight years of age, office worker. Coincidently with the onset of her last menstrual period, March 1, 1919, she suddenly became excessively nervous, could not sleep at night and was in a state of depression which made it impossible for her to attend to business. She believes her menstrual period was quite normal and that she did not suffer at that time 36 EPIDEMIC ENCEPHALITIS or previously from illness which in any way resembled influenza. In fact, she is quite certain that she had not had the influenza during the past winter; and up to the time of her present illness she had been carrying on her work with her usual energy and application. Almost imme- diately upon the onset of her illness, she noticed a great disquietude, especially in her lower extremities. She found she could not get them in any comfortable position but was compelled to move them about continually from one position to another. She also noticed that her move- ments became much more slow and deliberate and that whereas she had always been alert and active, she now felt stiff and fixed as if molded into an attitude out of which it was difficult for her to extricate herself. She had a definite sense of procursion and thinks that she could run ])etter than she walks. This proves to be the fact, and when she starts running it is difficult for her to come to a stand. Her attitude and expression are typically Parkinsonian; after the first week of her present illness, she observed a tendency to a tremor appearing in her hand, and more noticeably in her left foot. This sub- sequently extended so that it involved the entire left leg. The tremor came on especially when she was sitting down and when the leg was at rest. It was not notice- able while walking or standing. About this time there appeared over her entire l^ody a rash which she said was not unlike hives. A neurological examination made at the end of the fourth week of her illness showed a young woman looking and acting in all respects like a typical case of paralysis agitans. She sat immobile and then suddenly got up and walked about as if distressed, although her movements were slow. There was a suppression of almost all facial expression and of all automatic associated movements. CLINICAL AND PATHOLOGICAL MANIFESTATIONS 37 When she got up or sat down it was almost as if her body were one piece. She walked slowly with no automatic associated movements in the arms. Tests of coordination and skilled acts were normal, save for a marked slowing down of all movements. Her voice was monotonous and toneless. When at rest there was a definite Parkinsonian tremor in the left leg and foot. The reflexes were normal. There was some increase in muscle tone, especiall}' on the left side of the bod3^ All types of somesthetic sensibihty were intact. The Cranial Xerves. The olfactory sense was normal. The vision seemed fair; the fields were normal. The fundi showed a sUght blurring in the upper margin of the right disc. The pupils were unequal, the right l)eing larger than the left. The}' were round and regular and central in posi- tion. There was a slight hippus. Both pupils reacted to light and convergence, the left more actively than the right. There was no stra])ismus or other almormal move- ments of the eye. The acoustic nerve was normal and so also were the trigeminus, facial, glossopharj'ngeus and vagus, spinal accessory and hypoglossal nerves. The patient's mental condition became so distressing that it was necessary to send her to a sanitarium. Here she had several severe hysterical attacks, but subse- quently became calmer and has recently shown some slight improvement in all of her symptoms. This case has its interest in the fact that the Parkin- sonian sj-ndrome developed apparently without any background of general systemic involvement, there being no history of temperature or other signs of acute infection. Furthermore, the absence of any pronounced lethargy and the apparent substitution for it of marked restlessness, insomnia and physical disquietude give a 38 EPIDEMIC ENCEPHALITIS turn to the disease which is quite unusual when compared with the other cases of this type already reported. Case XI. Mr. G. G., sixty years of age, merchant. During the winter of 1918-19, he had the influenza twice, the first attack of which was complicated by lobar pneumonia. He made a complete and good recovery after each attack and was gradually regaining his strength when it was noticed that he began to lose his usual interest in his surroundings and lapsed into an apathetic condition. Every effort was made to arouse him from this state, but without success. He had no actual lethargy, but he slept much longer and apparently more deeply than was his custom. He would sit about the house most of the day without manifesting interest in his customarj^ pursuits. All of his motor activities became decidedly slower and more deliberate. His gait was somewhat shuf- fling in character and he noticed a desire when walking to hasten his steps; in fact he felt like running most of the time and could actually run much better than he could walk. His wife and friends noticed a pronounced change in his expression. His face had a fixed look. His voice grew feeble and monotonous. At the end of a month, it was difficult for him to get about, not alone because his movements were slow, but also because of the great fatigue which any muscular exertion caused him. Neurological examination at this time showed a well- preserved and robust man lying supine in bed, unable to rise without assistance, and quite as unable to turn himself from side to side in bed. He complained bitterly of a sense of disquietude in his legs, and expressed the wish to move them frequently about in the bed. In this way only was he able to be comfortable. His coordi- nation was normal. There was no tremor in any part of CLINICAL AND PATHOLOGICAL MANIFESTATIONS 39 his body. His reflexes were equal on the two sides, both deep and superficial, and no pathological reflexes were observed. Upon testing his muscles, the tone presented a marked increase in all of the muscles of both upper and lower extremities. All automatic associated move- ments were suppressed. Somesthetic sensibility was normal. Cranial Nerves. The nerves of special sense were intact. There was a slight weakness and flattening of the right side of the face and the patient reported that in the early part of his illness he had suffered from a transitory diplopia. The trigeminus, glossopharyngeus and vagus, spinal accessory and hypoglossal nerves were normal. On the day of the examination the patient manifested a ten- dency to sleep, which was more pronounced at this than at any other time during his illness. He had no tempera- ture; the pulse and respiration were normal. At no time during his illness had there been fever or other evidence of systemic disturbance. The laboratory findings were not reported in this case, and the patient has remained in practically the same condition for the past few weeks. This group of cases has its chief interest in the fact that all developed clearly defined Parkinsonian symp- toms. Four of these cases, in addition to the suppression of the automatic associated movements, the slowness of somatic movement, the characteristic attitude and facies, presented the agitans tremor. One case, however, having all of the other cardinal symptoms, had no tremor. Two of the five cases developed a moderate degree of somnolence during the course of the disease; on the other hand, three of these patients showed a marked restless- 40 EPIDEMIC ENCEPHALITIS ness, not onlj^ at the beginning of the disease, but more or less throughout its entire course, a fact which makes them stand out in contrast to the other types of epi- demic encephahtis already described. One of these cases ran a fatal course after several weeks' duration, with a marked sustained elevation of temperature and a sharp rise during the few days pre- ceding death. One patient died due to an intercurrent operation. One made a rapid, complete recovery, and two others are still suffering from the effects of the disease. Three of the patients had suffered from an attack of influenza a short time before the onset of the encepha- litis; two, however, did not give any such history. CHAPTER V POLIOENCEPHALITIC TYPE In this subgroup, of which many instances have l)e(>n reported, the authors have encountered two cases. This group is recognized because the essential symptoms of the disease confine themselves almost wholly to the local results of the polioencephalitis, usually of a light grade, and causing a paralysis of one or more of the cranial nerves. The oculomotor (third nerve) and the facial nerve are most connnonly affected, either in com- bination or separately. Lethargy, stupor or somnolence were not prominent in this group, although a pronounced asthenia of considerable duration was such a conspicuous clinical feature as to lead to the supposition that the eases might in reality be myasthenia gravis pseudopara- lytica. Upon investigation, however, it was definitely shown that such was not the fact and that cases of this polioencephalitic tj'pe belonged, in all probability, to a mild or even abortive form of epidemic encephalitis. Case XII. Mr. A. L. Age sixty-three, married, mer- chant. In January 1919, after many months of active and exacting business engagements the patient became so extremely exhausted that he consulted his ph^^sician. He was advised to give up business for a time and leave the city in order to rest and get the benefit of a complete change. The following morning his physician was again called, because the patient said he was suffering from some disturbance in speech which he thought to be 41 42 EPIDEMIC ENCEPHALITIS aphasia and probably due to a stroke. He was particu- larly alarmed because on the previous evening when he had been at the theatre, he was struck by the fact that he was troubled with double vision. This diplopia per- sisted until the next day, although in the morning upon waking up he found he was quite free from it. It returned, however, after he had attempted to read the morning papers. At this time when seen by his physician it was noticed that he presented a bilateral facial paralysis involving all three branches of the facial nerve on both sides. This paralysis accounted for his difficulty in speech, for he talked as one would if a finger were pressed into either cheek. A slight degree of ptosis of both upper eyelids was also present. He was advised to leave the city at once for the seashore. This trip, however, was not successful, for on the second day his asthenia in- creased so much that he became alarmed and had what seems to have been a nervous chill, with acute indigestion. Neurological examination at this time showed a man in a much enervated condition, fully cognizant of his environment, able to be up and about, and thoroughly to cooperate. His gait showed nothing peculiar, but his face had the characteristic expression of a bilateral facial paralysis. There was a marked epiphora of tears and a tendency to sialorrhea. His gait was normal. Mus- cular strength and coordination were good. There were no defects in skilled movements. His reflexes, deep and superficial, were normal and active. There were no ab- normal, involuntary acts, such as tremors or twitchings, and all automatic associated movements were intact. General sensibility was normal, as were all of the cra- nial nerves with the exception of the seventh on both sides. The electrical reactions of the facial muscles, both direct and indirect, showed a fairly active response CLINICAL AND PATHOLOGICAL MANIFESTATIONS 43 to the faradic current and the normal galvanic contrac- tion formula. The asthenia which was such a pronounced symptom in the early part of the disease has gradually disappeared. The facial palsj^ is slowly improving, although this has persisted for sixteen weeks. Case XIII. Air. A. G. A., thirty-six years of age; clerk. During the time when a number of patients were confined in a suburban hospital suffering from the in- fluenza, this patient was admitted because he had been slighth' delirious and had had a rise of temperature to 102° which lasted for several days. Upon the disappear- ance of the acute symptoms he manifested a paralj'sis of both oculomotor nerves leading to a slight degree of ptosis and external strabismus. The right side of the face showed some flattening in its middle and lower portions, while the activit.y of the frontalis upon the right side was less vigorous than that upon the left. This patient developed no further sjanptoms, and a neurological ex- amination made on the fourth day of his illness showed no evidence of pathological changes in his nervous sj's- tem other than those which have already been noted. He suffered from an asthenia of a mild grade which lasted for about a month. His blood, spinal fluid and urine showed nothing abnormal. In six weeks he was sufficiently improved to enable him to return to his business, and since that time, with the exception of a brief attack of severe sciatica on the left side, he has enjoyed normal health. Both of these cases may be taken to represent the strictly focal expression of a polioencephalitis of mild degree. The inflammation touched the nervous system but lightly and in restricted areas. In one case the in- 44 EPIDEMIC ENCEPHALITIS volvement of the cranial nerve nuclei was of considerable sevei'ity and determined a slow convalescence; in the other instance, however, the affection of the motor cells must have been slight, for the recovery was rapid and complete. These cases may, therefore, be taken to indi- cate the possibility of an abortive form of the disease, one in which the involvement is so light as to occasion a transitory clinical outline of the more severe type and to permit a restitutio ad integram almost before the symp- toms were well enough defined to attract attention. In one case there was a general systemic reaction as shown by the slight rise in temperature; in the other case no such reaction occurred. It is of further interest to note that in neither case was it possible to obtain a history of influonza. CHAPTER VI ACUTE ANTERIOR POLIOMYELITIC TYPE Case XIV. Over a year ago one of the authors''^ re- ported the case of a child four years of age whose mother stated that he had wasting of the right leg, dragging of the right foot, and weakness of the right leg, particularly when walking or running, and especially when walking any distance. This child's trouble occurred during the last epidemic of poliomyelitis which swept over New York City in 1916. The child left New York for Liverpool in September, 1916. On the last days of his trip he com- plained of feeling ill and his body seemed hot. He was seen by an English physician, who made the diagnosis of infantile paralysis, upon hearing that the child had come from New York. On the second day of his illness, the patient passed into a deep sleep, in which condition he remained, not even arousing to take food, for the next fourteen days. The mother took the child to the hospital and placed him upon a bed on his right side. Each time she called to see him he was still in the same position. After fourteen days the boy made his first sound, calling his mother. The child was unable to hold up his head without assistance for six weeks. He sat up alone for the first time in February, 1917, and two weeks later he was able to stand. Since that time he has gradually improved, the right leg remaining much smaller and softer than the left. With the exception of considera- ble atrophy and a marked hypotonus of the right lower extremity, the neurological examination made in 191.S 45 46 EPIDEMIC ENCEPHALITIS showed nothing abnormal in the patient. There is no record of the patient's hospital findings, so it is impossible to state whether the child suffered from an ophthal- moplegia or whether he had any cranial nerve involve- ment. At the time the case was considered to be one of acute poliomyelitis, and this opinion was undoubtedly greatly influenced ])y the fact that the illness occurred during a wide-spread and virulent epidemic of this dis- ease, during which clinical imagination was, perhaps, too keenly alert in the recognition of the disorder then epidemic. This condition of prolonged somnolence associated with a lower motor neuron type of paralysis affecting the leg, created much discussion, although it was the final opinion of the physicians who had an opportunity to study the case that the diagnosis was an atypical polio- myelitis. In no other way did it seem possible to explain the unusual and prolonged somnolence. It is our present belief that the case does in reality belong to that latter group and presents that rare but not at all impossible combination of symptoms, namely, the simultaneous involvement of brain and spinal cord. It is noteworthy, however, that in the majority of cases of encephalitis, the spinal cord is but little involved, and conversely, by far the greater proportion of acute poliomyelitis cases show little or no involvement of the brain stem. Par- ticular emphasis is laid upon this fact, and the authors desire to call special attention to this case of infantile paralysis which occurred during the height of a virulent epidemic of acute anterior poliomyelitis and yet had one of the most prominent symptoms associated with epi- demic encephalitis, i.e., prolonged somnolence. CHAPTER VII POSTERIOR POLIOMYELITIC TYPE So far as the recorded cases show at the present time, this type presents a unique variety of the disease whose chief characteristic is an inflammatory affection involv- ing the dorsal root gangha — in other words, producing an acute posterior pohomj^elitis. The authors have encoun- tered but a single instance of this tj^pe. Case XV. Miss M. S. Age thirty-nine years. The pa- tient's previous history is not important in her present condition. She has suffered from no serious illness, and so far as she is able to state, did not have influenza during the past winter. Her family history is negative. On January 1, 1919, the patient attempted in the morning to arise from bed, but upon standing up, fell to her knees, and only with great effort was she able to return to bed. This incident did not seem to have alarmed her much or to have attracted her attention especially. She knew that she felt weak and sleepy and so decided to remain quiet. In a short time she fell asleep and for the next three weeks, she slept most of the time. She could be aroused to take her meals but manifested little interest in her surroundings. When seen by her physician, her condition was thought to be one of a nervous break- down, possibly an hysteria. Her temperature was not taken and it is believed that she had no elevation of temperatuie during her acute illness. As she began to recover at the end of three weeks, she noticed, upon 47 48 EPIDEMIC ENCEPHALITIS attempting to read, that the letters blurred, and when looking at a distance she was conscious of double vision. This, however, rapidly disappeared, so that in the course of a week she could read for a short space of time without seeing double; but as soon as she became at all fatigued, the double vision returned. She also noticed a tingling and burning sensation which was very disa- greeable and at times painful upon the left side of her face in an area which came exactly up to the midline and followed in all its boundaries the cutaneous innerva- tion of the trigeminal nerve. In the region in which she suffered this painful sensation, there appeared a number of small herpetic-like eruptions which, however, never assumed the full character of herpes; these small erup- tions were very sensitive to the touch, to the air and to cold water. At the end of ten weeks the rash was still faintly visible and was discretely limited to the area of innervation upon the skin of the left trigeminal nerve. About this time the patient began to complain of a ting- ling and burning sensation on the dorsal aspect of the right leg, corresponding to sacral dermatomes 2, 3 and 4. This she described as similar in all respects to the sen- sation in the left side of her face, although no eruption had as yet been detected in this area on the right leg. The neurological examination showed that the reflexes were equal and active upon the two sides, both deep and superficial. The muscle tone was normal. There was no paralysis or loss of strength and no incoordination. The muscular status was normal. Somesthetic sensibility, with the exception of the left trigeminal area and the regions of innervation correspond- ing to sacral dermatomes 2, 3 and 4 upon the right leg, was normal. In addition to the pain and dysesthesia described in the two affected cutaneous zones, there was CLINICAL AND PATHOLOGICAL MANIFESTATIONS 49 a marked hyperalgesia in the trigeminal area of the left side and the cutaneous zones on the back of the right log. Paresthesia was also present in these regions, both cold and heat being interpreted as pain, and a slight stroking with cotton wool giving a distressing sensation. This case, whose cardinal symptoms were lethargy, ophthalmoplegia and zoster-like involvement of the left side of the face and the right leg, may be regarded as a typical example of acute encephalitis. Its unusual clini- cal feature arises from the fact that the dorsal root ganglia, certainly the Gasserian upon the left side and probably the dorsal root ganglia of sacral 2, 3 and 4 upon the right side, had been involved in an inflammatory process. CHAPTER VIII EPILEPTO-MANIACAL AND ACUTE PSYCHOTIC TYPES Case XVI. Mr. G. H., thirty-six years; clerk. In the latter part of December, 1918, this patient suffered from influenza with severe bronchial involvement. His recovery was unsatisfactory, for the reason that he seemed to pass from a respiratory to a psychic disturbance. In the second week of his illness, he became unmanageable. His tem- perature still remained at 102° and 103°. He had some hallucinosis as well as certain ill-defined, unorganized delusions. These were more troublesome at night, for during the day he slept most of the time. For several weeks he lay in this lethargic condition, occasionally during the day muttering some incoherent words or showing a partial cooperation when aroused to take medication or food. At this time he was orientated to time, place and person. At the end of two weeks his somnolence during the day became more profound, while at night his delirium would rise at times to a point at which he became violent and destructive, so that actual restraint was required. During these periods of excitement he manifested definite hallucinosis and delusions, the latter being mostly of the persecutory form. On several occasions he managed to free himself from his restraint and presented such maniacal manifestations that it was necessary to overcome him by force and keep him under the influence of narcotics. In the fifth week of his illness, he had a generalized, epileptiform convulsion, which was repeated in several hours, and from that time until his 50 CLINICAL AND PATHOLOGICAL MANIFESTATIONS 51 death, these convulsions continued with increasing frequency and severity. His temperature slowly rose and after being in a status epilepticus for several hours, he died in coma after an illness lasting six weeks. Neurological examination of this patient showed noth- ing of localizing significance. The motor system in so far as it could be adequately investigated, was normal, except for a slight external strabismus of the right eye, together with some nystagmoid movements affecting both eyes. The blood count and culture were negative on several tests. The first lumbar puncture showed a spinal fluid under considerable pressure containing a slight increase in cells. Upon smear and culture it revealed the presence of an organism which was regarded as a diplostrepto- coccus. This finding, however, should be accepted with much reservation, since the spinal fluid withdrawn several days later and tested in three different labora- tories, gave no such results. No autopsy was obtained. ACUTE PSYCHOTIC TYPE Case XVII. F. S., male, age thirty-six. Admitted to the hospital October 19, 1918, with a diagnosis of in- fluenza and bronchopneumonia, and the final diagnosis of acute encephalitis and acute parotid sialadenitis. On October 15, 1918, the patient was seized with a chill and general malaise. He felt some weakness and had headache and fever with pain in the back. On exam- ination, the patient presented much prostration, flushed face and rapid breathing; he had a coated tongue and a red pharynx. There were signs of bronchopneumonia in the lower right lobe posteriorly. There was some abdominal distension. 52 EPIDEMIC ENCEPHALITIS Neurological examination showed a patient very- apathetic, lethargic and difficult to arouse. There was nothing abnormal in the cranial nerves. The patient seemed unable to protrude the tongue. Examination of the blood made on October 21st, showed the wh:te cells 7,200; polymorphonuclears 96 per cent; large mononuclears 2 per cent and lymphocytes 2 per cent. The patient slept all of the time and was too somnolent to cooperate in any examination. There was some evidence of parotitis. He could be aroused from his lethargy with difficulty, but when he responded at all his answers and actions were irrational. During the next week his apathy and somnolence increased steadily, although there were intervals, especially -at night, when he gave evidence of an acute psychosis. He evidently suffered from auditory hallucinosis, as he seemed to hear voices and reply to them. Consciousness was much clouded and the patient became entirely disorientated during such intervals as when he was aroused to take food. During the night he manifested a vicious tendency to resist all efforts to care for him. He would get out of bed, urinate on the floor, and insist on throwing the bed- clothes on the floor or out of the window. If left to him- self, he would wander about the ward. Ultimately he became noisy and uncontrollable. On the 28th of October, the lethargy had deepened into a stupor. A lumbar puncture made at this time showed a clear fluid under no increase of pressure, with 4 lymphocytes, globulin reaction negative, Wassermann reaction negative, culture sterile. It now seemed impossible for him to articulate or to move his tongue and swallow. The reflexes in the upper extremities were present but sluggish. The ab- dominal reflexes were all present but sluggish. The itftli c. ' ; D.v'fiiMk Day 0/ 1U»4U UnrofD^ PUL.. Tui. 170 108«- 160 107?^ .1 1501 106a o; 1 1/3 ■ 40,' 1 1055- ■lb uo 1042. i*) 120 103?^ %<> 110 1025 »l 100 lOU Ik 90 100? X\ 80 99? IC> ;o 9«^ .0 970 ^ , ^ - lo.. "-r " a as 30 as as 30 _>»_ as 1 15 » U^tfD^ |g S ■ Imm III ' \ _1^. - 1 _j_ ' ;■[ ' i i 11 it ,» ... ■ 1 ' ■ 1 M ■ ' 1 ■ '■ ■ 1 - 1 ' . 1 ■ 1 J_ J_ ' j ' ' hi~ ' i i ; : .,. I 1 ■ ' : " : 1 1 i 11 II 1- ! 1 ■ i : ii! ! ! 1 ' 1- ~[ ^...'■\., Mill 1 iM ! M , : i 1 I 1,1 1 ■ ' 1 ■! Ill: 1 i ' ■ 1 , .^...^ ,^ , 1 1 ! ! ; i i !■ i ■ i 1 1 1 ' 1 hi' Roffl - • N'C- ^i/S^ w iP '■■ 1 I ! ; . -■■u .__._ - I';,'' 7'\ 'i I ' ' ' l/-"- \\''\ 1. 1 ' : •; 1 'a ■ ^:'d "' I ^m^ 1/1 /\ l"-! r 1 • ! ■' i ■ , li Mi', 1 i 1 ; 1 ' ■ ' !■ ' II t , :'"' ..:,/ ■ i ! ' I ■ ! ■! 1 ' : Hi .' il +^'^ 111: p ' ■ ■ , !■' ; M ■ 1:* :,: : |.; ' 1 .| l: 1 ! 1 1 1 1- ■ ■1 l;l:i' i i.:i IN ! ■ ; ! 1 i :. ; 1 ; . 1 ■:-' 1 1 . .■■ ; , 1 1 M-:'-i CHART III. ACUTE PSYCHOTIC TYPE CLINICAL AND PATHOLOGICAL MANIFESTATIONS 53 knee-jerks were present but feeble, the right being shghtly more active than the left. There was no Babinski nor any modification of this sign. The pupils were dilated, regular and equal, but reacted sluggishly to light and accommodation. The optic discs were sharply outlined. His temperature is shown in Chart III. On October 30th the patient passed into coma, and on November 1st died. No autopsy was obtained. CHAPTER IX « INFANTILE TYPE (NEONATORUM) It seems fitting in this subgroup to mention the cases of three infants, respectively four, four and six weeks of age; all of these cases were seen at the Babies' Hospital through the courtesy of Doctors Robbins and Gold- bloom, who are p/eparing a carefully detailed report for later publication. In the clinical picture, these patients corresponded so exactly to the conditions seen in aduUs suffering from acute encephalitis, that there can be little doubt as to the pathology of their disease. The interest of the cases lies in the fact that their disease began at such an extreme early age, an observa- tion, so far as the writers know, to which attention has not been hitherto called. Case XVIII. This infant, six weeks old, without premonitory symptoms, suddenly refused to take nourishment and passed into a deep sleep in which he remained for two weeks. During this period it was necessary to feed him by tube. Due to the excellent care which he received, he was kept alive, but when he began to show a return of interest, it was found that he had a complete paralysis of the left side of the face. This paralysis has persisted for a number of weeks although it is slowly improving. Case XIX. This patient, four weeks old, gave a similar history to that of the one already described and after a period of three weeks' somnolence, ])ogan to 54 CLINICAL AND PATHOLOGICAL MANIFESTATIONS 55 recover. In this instance, the lower and middle facial muscles upon the left side were found to be paralyzed as a result of the disease. The child is now doing well and is gradually improving. Case XX. Another infant, four weeks old, had a similar history of prolonged somnolence for two weeks, at the end of which time it began to show some return of interest. Subsequently it was found to be suffering from a paralysis of the left side of the face and a motor paralysis of the right musculo-spiral nerve, giving rise to a characteristic wrist drop upon that side. These three cases are cited in brief abstract only as they will be described later in extenso by the pathological department of the Babies' Hospital. The writers desire to express their deep appreciation of the courtesy and kindness of the staff of the Babies' Hospital which made possible the observation of these three cases. CHAPTER X DISCUSSION Critical Analysis of the Symptoms and Course of the Disease in the Series of Cases Described 1. Onset. In genei'al it may be said that the onset of epidemic encephahtis is sudden and usually occurs with- out the development of prodromata. Eighteen of the twenty cases described in this article showed such a sudden onset, while in the remaining two, there was a short prodromal period characterized by general malaise, asthenia, slight chilliness and a rise of temperature. This lasted for several days before the definite symptoms of the disease were recognized. 2. Lethargy. Profound somnolence approaching stu- por was the most common clinical feature in the group of cases described. This lethargy was characterized by the fact that although the patients seemed to be sleeping soundly and to be oblivious to the incidence of ordinary stimuli, they could be aroused by more active stimula- tion and would then, for a short time, manifest a fairly clear orientation and show little or no clouding of con- sciousness. This alert state, however, was short lived and as soon as the effort to keep the patients awake ceased, they would lapse back into the deep sleep again. The lethargy was of varying degrees of intensity; in some instances it was extremely light, being little more than a continuous drowsiness from which the patients could be aroused without much difficulty. In other cases, how- 56 CLINICAL AND PATHOLOGICAL MANIFESTATIONS 57 ever, the somnolence was much more profound and it required an active effort to awaken the patients. Seven- teen of the cases suffered from this lethargy, while three of them, although typical of the disease in other respects, at no time showed an inclination to sonmolence or drowsiness. It is interesting to note in this connection that all three of these cases belong to the type described in the subgroup of paralysis agitans. 3. Cranial Nerve Palsies. A large percentage of the cases showed involvement of one or more of the cranial nerves, fourteen of the cases presenting such affections. Of these, seven were confined exclusively to the oculomo- torius nerve (the third nerve). Six cases presented a combination of the oculomotorius and facial nerve palsies, and in one case, which rapidly ran a fatal course, the third, sixth, ninth, tenth and twelfth cranial nerves were simultaneously involved. In all instances, the cranial nerve palsies were of the lower motor neuron type. Six cases of this series presented no cranial nerve involvement. 4. Temperature. Some degree of pyrexia was the rule. It is, however, not an essential feature of the disease. Numerous observers have reported cases in which no temperature has been observed throughout the entire course of the illness. On the other hand, it is quite possi- ble that some degree of fever of short duration may be present in all cases but escape detection, in much the same way as in poliomyelitis, of which there are cases reported without elevation of temperature. This may be due to the fact that such cases did not come under observation at a time when the temperature might be accurately determined. It seems probable that all cases, even of the milder grades, are subject to changes in temperature at some time during the course of the disease. 58 EPIDEMIC ENCEPHALITIS Of the twenty cases of this series, fourteen ran a sus- tained temperature beween 101° and 102°, with several instances showing acute exacerbations much above this level for a number of days and, indeed, a few of them for a number of weeks. In the lethargic type a temperature averaging 102° seems to be the rule. There may, more- over, be sudden elevations to a much higher level (105°, 106° or even 107°), the temperature range having the appearance already shown in Charts I, II and III. The acute psychotic and epilepto-maniacal types show a tendency to a decided rise in temperature which is maintained for a considerable time. Of the five cases of paralysis agitans type, one alone showed a distinct and prolonged elevation of temperature. This proved to be a fatal case. In the milder cases of the lethargic type, the elevation of temperature is usually of short duration. In the more severe cases, however, the temperature curve may run a course coincident with the lethargy and begin to show an inclination to return to normal only as the patient recovers from the somnolence. In those types of the disease in which the inflamma- tory process is confined to the brain stem, the tempera- ture does not seem to reach an unusually high level, even in fatal cases, while in the posterior poliomyelitic type the temperature rise may be so evanescent as to escape clinical record. Such cases of the infantile type as have been observed would lead to the supposition that the pyrexia is not pronounced and is usually coincident with the duration of the somnolence. The pyrexia seems to vary directly with the intensity of the infection, both as to the degree of its elevation and its duration. CLINICAL AND PATHOLOGICAL MANIFESTATIONS 59 5. Tremor. Seven of the twenty cases presented a distinct tremor. In five of these, the tremor in its rate, amplitude and general conditions was of the paralysis agitans type. In two cases, on the other hand, it was of a much finer variety and made itself apparent either when the patient attempted to move a part or limb, or when the same was passively moved. The striking appearance of certain of the other cardinal features of the Parkin- sonian syndrome in conjunction with the tremor aided in establishing the identity of the tremor itself. The wax-mask expression, the suppression of automatic associated acts, the Parkinsonian attitude, the monotony of the voice, the flexible hypertonus of the muscles, the shuffling and festinating gait, were so unmistakable as to leave no doubt with reference to the clinical picture. In every instance, the distribution was that of a hemi- tremor, in two cases involving the right side and in two others the left side of the body. It was a tremor of rest which usually disappeared when the patient was in deep sleep but in nearly every case would make its reappear- ance when the patient was sleeping lightly or was about to awaken. One case had all of the characteristics of a paralysis agitans sine agitatione. Such tremor, therefore, as was noted, belonged for the most part to the paralysis agitans type, although a finer and more rapid oscilla- tion should also be included in the description under this heading. 6. Asthenia. More or less profound and general asthenia was observed in six of the twenty cases; in fourteen, however, it was not a prominent symptom. In those instances in which it did occur, it was conspicuous for its long duration and also for the tendency for the muscular weakness with a sense of general debility to return upon slight exertion, even weeks after the acute 60 EPIDEMIC ENCEPHALITIS symptoms had disappeared. Some of these patients, when well along in their convalescence, have found it necessary to go to bed again for several da3''s at a time, because their usual activities completely exhausted them. 7. Restlessness. As if replacing the lethargy, restless- ness and a sense of disquietude, which led the patients to feel that it was impossible to get the body or limbs into any comfortable position, especially while at rest, was a symptom which occurred in five of the twenty cases. It is of interest to note that this restlessness and sense of disquietude were present in all but one of the five cases belonging to the paralysis agitans group, and the fifth case, showing marked restlessness, was that of a patient whose subsequent history seems to indicate that he is developing some of the features of the Parkinsonian syndrome. 8. Catalepsy. An unusual hypertonus in the muscular system determining fixed positions of the trunk and limbs as well as of the facial and lingual muscles, was a striking feature in two of the cases. This hypertonus produced a rigidity which had some of the elements of a fiexibilitas cerea. On the other hand, the total absence of any evidence indicating impHcation of the pyramidal system would seem to place the responsibility of this muscular change outside of the palliospinal connection. Indeed, this symptom has been credited to some extrapyramidal system. The hypertonus so generally seen in the paraly- sis agitans group of this disease undoubtedly has its explanation in the disturbance of the extrapyramidal connections. Furthermore, a slight but still discernible degree of hypertonus was observed in all of the lethargic cases, which might be looked upon as partial involvement of the extrapyramidal fibers. CLINICAL AND PATHOLOGICAL MANIFESTATIONS 61 9. Spinal Fluid. The spinal fluid was carefull}'- exam- ined in fifteen of the twenty cases. In only one of these was there anything observed which could be considered as possibly pathological. This occurred in the single case in which on one lumbar puncture a diplostreptococcus was found in the fluid upon incubation, on culture and in the stained smear. Subsequent tests of the fluid ob- tained on another lumbar puncture from the same case showed no such organism to be present. With this doubt- ful exception, the spinal fluid in all cases was sterile; it contained but a shght increase in globulin and there was no marked pleocytosis. In some of these facts, the labora- tory findings in epidemic encephalitis stand out in con- trast to the familiar features present in acute anterior poliomyelitis. Although no definite organism has as yet been found in the spinal fluid of the latter disease, the marked pleocytosis and increase in globulin have been taken as significant of meningeal irritation or inflammation. COURSE AND DURATION OF THE DISEASE The average duration of the disease in so far as it may be estimated at present, is about eight weeks. This figure, of course, included a number of cases which are still improving or have as yet shown little or no change for the better. Some cases, on the other hand, may terminate fatally after running a brief course of a few days or as long as nine weeks. Many cases with the severest symp- toms clear up rapidly. There is, however, a tendency for their symptoms to reappear and in one or two cases new symptoms have become prominent after the patient had made an apparently complete recovery. Of the twenty cases included in this report, 25 per cent terminated fatallj'. 62 EPIDEMIC ENCEPHALITIS These figures seem to represent a mean between the mortahty rate of Economo which was 54 per cent, that of Netter^^ which was 46 per cent, that of Wilson which was 15 per cent, and that of Hall^^ who lost none of his sixteen cases. Of the cases of this series who have survived, roughlj'' 15 per cent show a complete recovery, 20 per cent are improving slowly, and 35 per cent are either at present stationary or show some aggravation of their former symptoms. CHAPTER XI PROGNOSIS AND DIAGNOSIS Conservatism should be used in giving a prognosis in cases of any type of this disease. Some forms of it seem to be more prone to fatal termination than others. In general, it may be said that the poliomyelitic and mild polioencephalitic types are not serious with respect to life and usually terminate in a complete recovery after a relatively short duration. Cranial nerve palsies, how- ever, especiall}^ where the facial nerve is involved, are somewhat slower in repair than is the case with the ordi- nary peripheral facial palsies. Ophthalmoplegias are generally of short duration, but tend to reassert themselves for some time after recovery has been established, especially when the pa- tient becomes exhausted or fatigued. In the epileptomaniacal and acute psychotic types, the condition should be regarded as grave and not of hopeful prognosis as to life. In the lethargic type, one should be governed largely by the intensity of the somnolence. This however, is not the only index which may serve as a guide. Many of the most severe cases of this type make a good recovery and they should be considered as particularly grave only when the cranial nerves of the bulb give evidence of involvement. The prognosis in the cataleptic type is much better than the general impression which these patients actually convey during tlie period of tluMr illness. Their appear- 63 64 EPIDEMIC ENCEPHALITIS ance seems to certify a fatal termination, and yet a num- ber of these cases make a good recovery. In our series, one case of the cataleptic type is still living and one of them died. In the paralysis agitans type of the disease, it is perhaps too early at this time to state definitely what outcome may be expected in every case. It is quite certain that complete recovery from this type of involvement is possible, but whether all of the cases manifesting the Parkinsonian syndrome will eventually clear up is a question to which the material of this study cannot as yet give satisfactory answer. A number of other observ- ers, however, have reported cases of the paralysis agi- tans type in which complete recovery has eventually occurred. The infantile type of the disease (Neonatorum) seems to afford a fair outlook as far as the acute stage of the disease is concerned. Such patients as have been under observation survived the acute stage of the disease. On the other hand, all of these infants are still in a precarious condition since they suffer from the effects of a greatly impaired central nervous system which imposes a handi- cap upon them in meeting their somatic and visceral requirements. During the inception of the acute stage of all cases of epidemic encephalitis a guarded prognosis seems to be indicated. Other Types of Epidemic Encephalitis. A review of the literature makes it possible to recognize types of this disease other than those which have come under the observation of the writers; and while it is not yet possible to include these types in our series, they seem so well established in the experience of others, as to necessitate their inclusion here for the sake of completeness. CLINICAL AND PATHOLOGICAL MANIFESTATIONS 65 Among these are types which have been described as meningitic, polyneuritic, cerebellar ataxic, hemiplegic, diplegic and monoplegic. These varieties, together with those already mentioned in the series of cases under consideration, call attention to the protean character of the symptoms, a fact which accentuates the probability that no portion of the nervous system is exempt from the pathological changes of the disease. DIFFERENTIAL DIAGNOSIS The diagnosis of epidemic encephalitis is not without its difficulties. One of the writers was recently called to see a case of so-called "Sleeping Sickness" which had all of the clinical features of a typical case of epidemic encephalitis, even including the negative findings of the cerebrospinal fluid. Upon post-mortem, however, the case was found to be one of tuberculous meningitis. In another instance, a case which had acquired con- siderable reputation through the lay press as Sleeping Sickness, because of a trance-like state which had per- sisted for a number of weeks, finally showed a positive Wassermann reaction in the spinal fluid, although this test had on several previous occasions been reported negative. Under all circumstances, laboratory findings must be evaluated with much caution and always with particular reference to the known reliability of the laboratory from which the returns are received. Three classes of disease will offer some perplexity in the differential diagnosis. The first group consists of diseases in which the diagnosis is made by examination of the spinal fluid. 1. Tuberculous meningitis differs from epidemic enceph- alitis in that the spinal fluid is usuall}' under increased 66 EPIDEMIC ENCEPHALITIS tension, presents a pleocytosis and contains the tubercle bacillus. 2. Cerebrospinal 7nenvngitis of the epidemic type differs from epidemic encephalitis in the fact that the spinal fluid is cloudy or flocculent, contains many leu- cocytes, in some of which may be recognized the patho- genic organism of the disease, the meningococcus. 3. Cerehrosjnnal syphilis differs from epidemic en- cephalitis by the positive Wassermann reaction in the spinal fluid, a marked pleocytosis, increased globulin, and either a paretic or a luetic colloidal gold curve. The second group of diseases consists of those whose recognition will be aided by certain pathological tests. 1. Typhoid fever, the nature of which will be recog- nized by the Widal reaction, the temperature curve, the enlarged spleen and the rose spots. 2. Diphtheritic paralysis, whose chief differential feature is the discovery of the Klebs-I.oeffler bacillus in the throat and a history of suggestive diphtheritic infection. 3. Uremia, in which the routine tests of the urine show an albuminurea or the presence of renal casts. These findings may be substantiated by an estimation of the blood urea or of the renal efficiency by the phenol- sulphonaphthalein test. 4. Botulism. This condition is distinguished by the presence of the bacillus botulinus in the food par- taken by the patient immediately prior to the on- set of the disease and by the acute gastrointestinal disturbances. The third group represents conditions which may be distinguished by their clinical features: 1. Hysteria, is recognized chieifly by the presence of hysterical stigmata, the absence of pyrexia and the CLINICAL AND PATHOLOGICAL MANIFESTATIONS 07 presence of marked sensory disorders, such as hemian- aesthesia or a contraction of the visual fields. The presence of normal reflexes and the absence of true palsies, nystagmus and other oculomotor disturbances are also significant. 2. Cerebral tumor, a diagnosis made in one of the twenty cases of the present series, may be differentiated by the absence of optic atrophy, papilledema, vomiting and paroxysmal headache. 3. Acute dementia is distinguished by the persistence of maniacal delirium unaccompanied by stupor or pyrexia. CHAPTER XII NATURE OF THE DISEASE (Whether this is a new disease or a recent outcropping of an old epidemic tendency is a much debated subject. The occurrence of prolonged and profound sleep in connection with epidemic diseases is not new in medical history. Such somnolence has been described in connec- tion with many epidemics of influenza since the earliest times. Zuelzer^^ reports the fact that in an epidemic of influenza occurring in 1712, profound sleep was so fre- quent and pronounced a symptom that in Tubingen the disease came to be known as the Sleeping Sickness. In more recent times, Longuet^^ in 1892 gives an account of a mysterious disease known as "Nona" also "Nonna." This was said to have occurred especially in northern Italy and Hungary and to be characterized by lethargy and weakness. The derivation of the word "Nona" seems to be obscure; the name was given to an alleged new form of disease reported in 1890 in northern Italy, Bavaria and Russia. It appears, however, that there is little foundation for the belief that there is such a new disease, since the reports seem to be founded on cases of typhoid fever with coma or of somnolence following influenza as well as of smallpox of an irregular and severe form. A recent epidemic of lethargic encephalitis in Vienna was described by Economo in 1917, while Netter reported a similar outbreak in Paris in 1918. The report of an inquiiy into an obscure disease, Encephalitis 68 CLINICAL AND PATHOLOGICAL MANIFESTATIONS 69 Leihargica, made by a commission in London, in 1918, records the occurrence of 168 cases, together with a valuable analysis of this material, Wilson, Hall and others have also made records of a number of cases of this disease during the same period in London. In the latter part of 1918 and early 1919 the first cases appeared in America, and as had previously happened in England and France, it was several months before there was general recognition of the exact nature of the "sleeping sickness" we were observing. In all probability, this is not a new disease, but an epidemic whose presence has attracted more wide- spread recognition and more careful analysis than in the past. /^Epidemiologically, it must be regarded as an infectious disease, probably communicable. This, at least, is the attitude taken at present by the English authorities, for the disease has been made temporarily a notifiable one in England and Wales for the period of one year. The bacteriological evidence thus far adduced does not throw much light upon the pathogenesis of epidemic encephalitis. Von Wiesner, '^ studying one of Economo's cases, isolated a gram positive diplostreptococcus in 1917. This he was able to cultivate and the culture of it injected in a macacus rhesus produced somnolence with muscular weakness, while peritoneal injection into guinea pigs caused death from internal hemorrhage. A filtrate from the original brain-cord emulsion of the patient through a Berkfeldt filter injected into a macacus rhesus produced no symptoms, although an unfiltered emulsion of the brain and spinal cord injected subdurally into the same species caused death in forty-six hours, the animal having previously presented profound stupor in addition to a paresis of the right hind leg. 70 EPIDEMIC ENCEPHALITIS Mcintosh^* examined two cases and found in one a gram positive motile nonproteolytic anaerobic bacillus which resembled the vibrion septique of Pasteur. In the other case, there was a gram positive non-motile anaerobic bacillus which belonged to the bacillus Welchii group of anaerobes. He found no bacillus botulinus and no pleomorphic coccus such as described by Rosenow^^ in acute anterior poliomyelitis. Mcintosh injected emulsions of the basal ganglia, pons, medulla and cervical cord intracerebrally and intraperitoneally in macacus rhesus but produced no results. In this respect, his find- ings are in direct contradiction to those of von Wiesner. Cultures from the blood and spinal fluid were sterile, as were also those taken from the excreta of the naso- pharynx and from the feces. Sera of recovered patients injected into mice did not protect these animals against injections of botulinus toxin. MacNalty^^ suggests that epidemiologically, clinic- ally, and pathologically, epidemic encephalitis differs from classical poliomyelitis and is, in fact, a disease sui generis. MacNaltj^ suggests that the relation of epidemic encephalitis to poliomyelitis may possibly be that of typhoid fever to paratyphoid. The pathological study of a number of cases establishes the fact that the tissue reaction due to the infection is an actual inflammation. Marinesco^^ has pointed out that epidemic encephalitis may be differentiated from the changes of botulism and the alcoholic polioencephalitis of Wernicke by the fact that in these latter diseases the changes are not those of a true inflammation but rather due to profound alterations in the vessel walls, leading to secondary degenerative processes in the nerve tissue. He also calls attention to the fact that although the true sleeping sickness may resemble epidemic encephalitis CLINICAL AND PATHOLOGICAL MANIFESTATIONS 71 in many respects, its differentiation depends upon dis- covery of the trypanosoina gambiensc. Marinesco and Mcintosh both allude to what they deem essential pathological differences between acute anterior poliomyelitis and epidemic encephalitis. In poliomyelitis, for instance, the distribution of the lesion is largely confined to the cord. The pia-arachnoid, as a rule, shows considerable involvement, while the changes in the brain are slight. In encephalitis, however, the greatest changes are in the basal ganglia and nuclei of the brain stem, the gray matter of the floor of the fourth ventricle and around the aqueduct of Sylvius. The pia-arachnoid is but little involved and changes in the spinal cord are rare. The character of the cellular infiltration in the two diseases is also a distinguishing feature. In poliomyelitis, polymorphonuclear leucocytes predominate and plasma cells are of less frequent occurrence. Hemorrhages are common and relatively large, while the vascular changes affect the smaller arteries. In encephalitis, plasma cells are much more common, while the polymorphonuclear cells are rare. Hemorrhages when present are usually microscopic. The infiltration is adventitial about the small vessels and more especially the venules. The cellular changes in the two diseases are somewhat different. In poliomyelitis, degenerations are pronounced and neuronophagia is active, while in encephalitis the cells are not much involved ; such changes as do occur are relatively mild and neuronophagia when present is not marked. The clinical differences between poliomyelitis and epidemic encephalitis have been emphasized by Wilson and MacNalty. 72 EPIDEMIC ENCEPHALITIS It seems justifiable to conclude, therefore, from ana- tomical, clinical, pathological and bacteriological evi- dence, that these two diseases are not identical, although they may be closely allied in their pathogenesis. Draper ^2 thinks epidemic encephalitis is strikingly like poliomyelitis in many respects, and may be a sub- group of the latter. He is of the opinion that animal experimentation alone, carried on upon a large scale, can give the solution to this problem. Much has been written concerning the relation of epidemic encephalitis to influenza. Many hints from the past and not a few confident assertions in the present aim to give these two diseases a single identity. There seems, however, little real basis for this position; but the question probably cannot be definitely decided until more is known concerning the exact pathogenesis of each of these clinical conditions. In the series of cases described by the writers, fifty per cent of the patients gave no history indicative in any way of influenza, unless it be conceded that the abrupt onset of cerebral symptoms without the occurrence of any of the more usual symptoms of influenza were an expression of this latter disease. It is not unlikely that the relation between these two diseases may be a mutu- alistic symbiosis, or that one may be metabiotic to the other. CHAPTER XIII TREATMENT No specific agent or remedj^ has yd been discovered in the way of serum or vaccine for deahng directly with the disease or affording immunity against it. (^During the acute stage in all types of epidemic en- cephalitis, the patient should be kept in bed and, since this is proba])ly a communicable disease, some degree of isolation should be established. Perhaps the barrier sys- tem or one in which nurse and patient are kept apart from the rest of the household, will suffice. All l^edding, cloths, utensils, etc., which come in direct contact with the patient, should be properly sterilized^ (The principle of treatment is essentialh' sjmiptomatic. For pyrexia, cold sponges or a light cold pack when the fever is 102 or over usually give the best results. Urotropine, 10 grains three times a day, is theoretically presumed to be of benefit and may be used in this amount or in increasing doses. Elimination is an important feature in the treatment; the bowels and kidneys should be kept active and flushed out as much as possible. For this latter purpose, high colonic irrigations of normal salt solutions should be given daily, or if this proves fatiguing to the patient, two or three times a week. As much water as possible should be administered bj^ mouth, and when this becomes diffi- cult, the continuous Murphy drip is advisable. Feeding should be careful throughout this period and 73 74 EPIDEMIC ENCEPHALITIS limited to a fluid diet. Frequent feedings of two to four ounces every two hours are preferable to larger quanti- ties at longer intervals. Unless otherwise indicated, the diet need not carry more than a medium calorie value and only in cases where emaciation is marked and rapid is forced feeding necessary. Repeated lumbar puncture has been advantageous in some cases, 10 to 20 c.c. of the fluid being withdrawn every three to five days. In the more profoundly lethargic and cataleptic cases, care should be taken of the skin to prevent decubitus, and when indicated, cardiac stimulants, such as digipura- tum and digalin, should be administered. Restlessness is frequently a difficult complication. This seems to be best treated by means of the bromides, the usual combination of ammonium and sodium of potassium giving good results, in doses of 10 grains each, well diluted, three times a day. For insomnia, 10 grains of medinol dissolved in warm milk, or 3 grains of allyl barbituric acid similarly ad- ministered at bedtime, usually produce sleep. For some patients, however, other similar remedies may be re- quired, since those mentioned may not be as eifective as certain other soporifics. For active or violent delirium, the most efficient remedy is paraldehyde in doses of 4 drams every four hours if indicated. In certain cases, however, as for exam- ple those in which the maniacal tendency is most devel- oped, the prolonged warm bath gives excellent results. This, however, should not be attempted by inexperienced attendants and should be under the direct supervision of the attending physician. In cases showing violence or active delirium, restraint should be avoided as much as possible. It is much less exhausting to the patient if he CLINICAL AND PATHOLOGICAL MANIFESTATIONS 75 be permitted to carry out, in part at least, the more or less indefinite purposes arising from the activity due to his delirium. If circumstances will permit, it is better not to attempt to restrain the patient in bed, but allow him some latitude, while surrounding him with the necessary protection against injuring himself or others. For the tremor, either of the agitans type or the more rapid oscillation, a prescription containing hyoscine hydrobTomate, gr. Mso with codeine sulphate }4 gr- may be given three times a day. For these cases, mor- phine is best avoided, and the bromides, if used at all, should be administered in small doses, that is, not exceeding 30 gr. a day. During the stage of convalescence, care should be exercised in not permitting the patient to get up and about too early. This error frequently leads to relapses and unnecessarily prolongs the asthenia consequent upon the disease. A partial rest-cure plan should be adopted when the patient is first attempting to get about. This should never be left to the discretion of the patient, but prescribed in detail, according to the hours of rest required, the amount of exercise or engagement in usual occupation and such other directions as seem necessary. During this time a simple nutritious diet and plenty of water are essential/) For the asthenia seen so frequently in these patients, an excellent remedy is suprarenal residue, 5 minims, three times a day after each meal. This may be best administered by mouth in combination with the hypoder- mic injection of cacodylate strychnia, gr. 3go ^very daj^ either with or without the arsenate of iron. During the stage of after-care of the palsy, especially the facial paralysis, much benefit may be had from daily facial massage and the application of the galvanic 7G EPIDEMIC ENCEPHALITIS sinusoidal current in mild strength directly over the facial nerve for fifteen minutes three times a week. The faradic current is of little use, especially in the early stages of the paralysis, when faradic response is generally absent. PART II CLINICAL AND PATHOLOGICAL STUDIES OF- SELECTED CASES CHAPTER XIV ETIOLOGICAL FACTORS AND CLASSIFICATION A ge. No age seems to be exempt, but the greater pro- portion of eases are in young adults. The age incidence in the different decades in 161 cases selected from the literature are as follows: Under 1 year 3 1 to 10 years 29 10 to 20 years 29 20 to 30 years 33 30 to 40 years 22 40 to 50 years 21 50 to 60 years 17 60 to 70 years 7 Sex. The sexes are about equally affected, but as in poliomyelitis there may be a slight preponderance of males. NeaP" reports 33 males in 40 cases. In 99 cases reported from civil practice, 50 were males and 49 females. Relation to Influenza. The relation of this disease to influenza has given rise to considerable discussion in this country. A large proportion of cases reported here had suffered from influenza at i3eriods varying from one week to six months previously. Occasionally encephalitis has followed immediately what was supposed to be influenza and some authors have considered it influ- enzal encephalitis. There has been little reference to the relation of these diseases in the foreign literature until very latelj^ as the epidemic of encephalitis ante- 79 80 EPIDEMIC ENCEPHALITIS dated that of influenza in both France and England. There seems to be but shght logical ground for consider- ing these two conditions as having any active relation to each other. As is stated in the description of the symp- toms of onset, they are very similar to and are frequently mistaken for those of influenza. Relation to Poliomyelitis. Its relation to anterior polio- myelitis is not easy to prove or disprove. They both seem to be systemic diseases the virus of which is probably lymph borne, and has a special affinity for the motor ele- ment of the central nervous system. The geographical distribution of the epidemic of en- cephalitis has been far more widespread than that of any epidemic of poliomyelitis, but it has not been so severe in any one small area. The method of transmission of epidemic encephalitis and poliomyelitis is absolutely obscure. There is growing opinion that direct contagion is not the mode of trans- mission of poliomj'^elitis, and there seems to be no evi- dence of contagion in the spread of epidemic encephalitis. Both French and British authors have observed that two cases have never developed in the same house. It seems not unlikely, however, that the virus producing both of these diseases is similar, but of different strain. Epidemic encephalitis presents certain differences from poliomeylitis which cannot be overlooked: It affects all ages, but more especially young adults. The palsies are usually less profound, may be variable and have more of a tendency to clear up. The localization is in the brain and brain stem rather than in the cord. The pathological changes are less severe : there is less evidence of meningeal inflammation; more of a tendency to hemorrhage; less severe inflammatory and degenera- STUDIES OF SELECTED CASES 81 tive changes in the nerve cells, and less marked neuronophag^^ Possibly the greatest difference between the two con- ditions is in the nature of the action of the virus on the nerve elements. In poliomyelitis there is a sudden, sharp attack which develops rapidly and in a few days attains the maximum of severity, quickly producing the greatest extent of destruction. In epidemic encephalitis the onset is frequently very gradual and the progress of the disease slow, in some instances requiring several months to reach its greatest severity, and even then the findings have a tendency to variability, being subject to exacerbations and remissions. CLASSIFICATION OF ANATOMICAL TYPES While no hard and fast classification can be made and none is necessary, still it may have some value in that the various forms not only have different symptoms, but also frequently have a different course and prognosis. In making a classification it is desirable to use as nearly as possible an anatomic basis. As a result of studying the cases described in the literature as well as those personally observed, I believe that most of them maj' be placed in one of the following groups: 1. Cases with general symptoms indicating involve- ment of the nervous sj'stem, but absent, scant or fleeting localizing signs. 2. Meningitic type. 3. Cortical tj'pe. 4. Pyramidal system type. 5. Thalamic type. 6. Corpus striatum (extra-pyramidal) type. 7. Brain stem type. 82 EPIDEMIC ENCEPHALITIS 8. Cerebellar type. 9. Spinal type. 10. Peripheral nerve type. 11. Multiple diffuse lesion type. As in poliomyelitis, there is also an abortive form, but it does not comprise a distinct group, as abortive cases may occur in many of the above types. GENERAL OUTLINE OF VARIOUS FORMS 1. Cases with General Sijmptoms. The cases in- cluded in this group frequently present in the early stages signs of cerebral irritation, restlessness, delirium, possibly hallucinations and delusions; later lethargy, stupor, and general muscular rigidity super- . vene. There is usually fever at the onset and at the end if the termination is fatal. The predominating features are the lethargy and stupor or coma, though there may be slight or fleeting evidences of cranial nerve involvement. 2. Meningitic Type. The meningitic form is charac- terized by the prominence of manifestations of menin- geal irritation, fever, headache, stiffness of the neck and a slight Kernig sign. 3. Cortical Type. I have not observed or seen reported any cases where findings due to cortical lesions predomi- nated, but isolated monoplegias and aphasias pointing to cortical localization are present, usually, however, in the type where the general symptoms dominate the clinical picture. 4. Pyramidal System Type. In this type signs of pyramidal tract disturbances are present. The onset may be a sudden hemiplegia. Later evidences of other STUDIES OF SELECTED CASES 83 lesions appear, especially those involving the cranial nerve nuclei. 5. Thalamic Type. There are no cases reported which show the typical thalamic syndrome; but ataxia and choreo-athetoid movements associated with lesions of structures in close proximity with the optic thalamus, point to thalamic involvement. 6. Corpus Striatum Type. Here are placed cases show- ing a more -or less typical Parkinsonian syndrome. Gen- eral muscular rigidity with irregular cogwheel release on passive movement, characteristic tremor, mask-like ex- pressionless facies, bowed, rigid attitudes and festinating gait. 7. Brain Stem Type. Involvement of some of the cranial nerves occurs in the greater proportion of cases of epidemic encephalitis. This group is limited to those showing the cranial nerve palsies as the principal feature. 8. Cerebellar Type. Cases where ataxia is the principal finding have been noted, but have not been clearly and thoroughly described. 9. Spinal Type. Signs of involvement of the anterior horn cells are frequently present. Cases presenting mainly this feature are described under the captions "anterior and posterior poliomyelitic types" (p. 45). 10. Peripheral Nerve Type. Involvement of the peri- pheral nerves is rare. A musculo-spiral palsy was observed in Case XX reported on page 55. 11. Multiple Diffuse Lesion Type. In this type the lesions are scattered profusely throughout the brain and cord. The cases included in this group show evidences of multiple localizing lesions but without predominating features which place them in any of the other groups. They may l)e clinically similar to multiple sclerosis. 84 EPIDEMIC ENCEPHALITIS In 116 cases sufficiently completely reported to allow of classification, the grouping is as follows : General type 28 cases Meningitic type 7 cases Pyramidal system type 5 cases Thalamic type 1 case Corpus striatum type 14 cases Brain stem type ■ • • ■ 45 cases Spinal type 2 cases Peripheral nerve type 1 case Diffuse multiple type 13 cases CHAPTER XV PATHOLOGICAL CHANGES Macroscopic. On the surface of the brain there may be no macroscopic changes except for a shght degree of vascular congestion over the cortex. Frequently there is frank congestion and a slight degree of meningitis which appears in scattered, irregular patches over the cortex or base. There may be small hemorrhages from the surface vessels between the layers of the pia. In the areas where there is meningeal inflammation the pia is thickened, less transparent, and of a grayish-red color. Tliis appear- ance is observed most frequently on the base of the brain in the neighborhood of the peduncles and in the inter- peduncular space. On section of the brain substance there are tinj^ red specks or streaks which may be diffusely scattered throughout the cerebral cortex, basal ganglia, cerebellum or brain stem. As a rule they are most promi- nent in the subthalamic region, the cerebral peduncles and in the pons. They are scattered promiscuously throughout the gray and white matter and may be due to small capillary hemorrhages; but on close examination many of them will be seen to be simply small vessels distended with blood. Throughout both brain and cord the congestion is more marked in the gray than in the white matter. In the brain stem the hemorrhages may be of larger size and at times are several millimeters in diameter. In the severe cases without pronounced local- izing signs minute punctate hemorrhages have been found profusely scattered in the gray and white matter of 85 86 EPIDEMIC ENCEPHALITIS the cerebrum, cerebellum, pons and medulla, but with- out particular localization anywhere. Microscopic. Changes are found both in tissues of mesodermogenic and of ectodermogenic origin. The pia mater in most areas is normal. Where it is involved it is ■-■■ '-^t' ■-.►-;'■*■-■■ :--%/i.;^V ■ — .r. ^■i - A:" ■'^^' ^■l■■' Fig. 7.— Thalamus. Diffuse Crllular 1 nliltiation. thickened, its laj^ers being separated by edema, cellular infiltration, and at times red blood cells which have es- caped from the pial capillaries. In the substance of the brain there is diffuse capillary congestion which is most marked in the involved areas. The Virchow-Robin spaces STUDIES OF SELECTED CASES 87 1' ^ ^ ■»■■ ■% #' ■' ■ * • - ■' ?*■ A ■ ■ •■< . '*^' ■< -^ • ', ' i'lii. >. — I naiaimis. i'loudy iSwollinu; m .\curuc\i('s. 88 EPIDEMIC ENCEPHALITIS of the vessel wall may contain red blood cells but more frequently show moderate distension with lymphocytes. Occasionally polymorphonuclear leucocytes are seen in the adventitial lymph spaces, but almost all of the cells are similar to the lymphocytes of the blood. The Fig. 9. — Thalamus. Acute Cloudv Swelliuii; of Xerve Cells. hemorrhages are frequently perivascular, that is, largely confined to the perivascular space of His. Some of them are larger, irregularly infiltrating the surrounding tissue. In some areas small collections of cells are seen which may be in either the gray or white matter and have no appar- STUDIES OF SELECTED CASES 89 Fig. 10. — Thalamus. Higher Magnification. Severe Degenera- tive Changes and Neuronophagy in Some of the Nerve Cells. 90 EPIDEMIC ENCEPHALITIS ent relation to a nerve cell or blood vessel. The cells forming these accumulations are largely ameboid glia cells, though in some areas lymphocytes are occasionally seen. Usually very few of the blood vessels show any infiltration of the adventitial lymph space, and unless 'i^i^ V'-'^ ■••';^v -v'is, v.-i»^-, .w -' --:r'i'-''- ':~-^^:'":^-.r >:*-''-i ', ', ; -'- - »_ "w» ■" ■"■■,"- ' - ' . T . -^ .-"^. "". -v. . : ''" ' .':■■■ ^ ■:'<■" jiJ - -■ . .'^ -^ -■_' , »,.^'-r' -.1 - . ^- ''l'->I^:^-'-:'"-->'''SS^ I^!^--^^*/ ':'■-'::■''■'--•'' Fig. 11. — Capillary Congestion in Internal Capsule Bordering on Thalamus. sections from many portions of the brain are examined, it may not be found. The alterations in the ectodermogenic or true nervous tissue are not as marked as in anterior poliomyelitis. The milder grades of acute cloudy swelling are found STUDIES OF SELECTED CASES 91 in some of the motor cells of the ponto-medullary nuclei. The nerve cells, except in the immediate neighborhood of inflammatory areas, however, frequently appear surprisingly normal, showing no evidence of chroma- tolysis or acute cloudy swelling. At times there is mode- rate neuronophagia, but it never seems to be marked and is frequently absent. The changes in the nerve cells show sharp contrast with those found in acute anterior poliomyelitis, where very severe grades of all variations of cell disintegration and destruction are seen. Marincsco observed cytolysis of the cells in the locus niger with the liberation of the melanic pigment, which was picked up by the neighboring phagocytes. Moderate degrees of acute cloudy swelling are found in the neuronocytes of the cortex, basal ganglia, brain stem and cord. There is solution of the tigroid substance, the cells are swollen, the nuclei eccentric, and occasionally there is satel- litosis and rarely neuronophagia. Vacuolization, ruptm-e of the cell membrane, and complete dissolution of the cell body with active pai-tioipatioii of phagocyte cells, are uncommon. CHAPTER XVI SYMPTOMATOLOGY The onset of the illness may be sudden, but the char- acteristic symptoms frequently do not appear for several days after the initial disturbance. Slight nasal discharge, headache, dizziness, generalized pain and aching, fever and sweating, often lead the physician to believe that the patient is suffering from influenza. A day or two later there is restlessness, loss of appetite, constipation, often vomiting, and possibly delirium at night. After a period varying from two or three to fourteen days, the symptoms gradually subside and an abnormal drowsi- ness ensues. In another week the drowsiness has passed into lethargy or stupor, and the headache, vomiting and fever usually disappear. Ptosis or other evidences of cranial nerve palsies then appear as well as other signs of general or localized involvement of the nervous system. While this description of the early symptoms is a com- mon one, at other times there may be no general pro- dromata. Drowsiness and listlessness may appear at first, while occasionally diplopia, ptosis or facial weakness are found. Rarely there are no evidences of a constitu- tional disorder, but there suddenly appears a hemi- plegia or other manifestation of a serious injury to the central nervous system. At times the picture is similar to that of meningitis; headache, hyperaesthesia, fever, stiff neck and an indefinite Kernig sign are found. Occasionally the onset may be so insidious that it is 92 STUDIES OF SELECTED CASES 93 impossible to determine the date of the first symptoms. Several weeks may intervene before the patient con- siders his complaint of enough importance to consult a physician. Gradual progressive weakness with possibly slight dizziness and headache may be the onlj^ symptoms Fig. 12. — Internal Capsule. Capillary Congestion and Character of Invading Cells. for several weeks. In the greater proportion of cases there is more or less marked muscular hypertonia and the whole body becomes rigid. All the active movements are slow, difficult, and often accompanied by a rather coarse tremor. Wax-like rigidity or catatonia is fre- 94 EPIDEMIC ENCEPHALITIS quently present, especially in the early part of the lethargic stage. Later the muscular rigidity may be as pronounced, but there is so great muscular weakness that the limbs cannot be maintained in any position which requires muscular effort. Passive motion elicits an irregular release or cogwheel resistance. In some patients peculiar positions are almost constantly maintained, as was evident in Case VI and Case X of Part II. This condition has been noted in patients presenting peculiar stereotyped movements. These movements have been described as choreo-athetoid, but possibly are more of a major tic. They consist in the constant repetition of a succession of move- ments or gestures involving one or moi-e entire member of the body. These movements cease during sleep, are increased by emotional excitement, and may be in- hibited or stopped for a short time by voluntary effort, but are otherwise constantly present. The localiza- tion of a lesion producing a movement of this character is difficult. It may possibly originate in lesions of the optic thalamus with irritation of the extra pj'ramidal motor apparatus; but, on the other hand, it seems difficult to believe that these coordinated and synergic move- ments could be initiated outside of the cerebral cortex. Uncontrollable laughter or smiling is sometimes present (Case IV) and maj^ cause distress to the patient. Speech almost constantly shows some alteration. It is frequentlj- weak, possibly little more than a whisper, being high- pitched, slow and monotonous. In the bulbar cases various degrees of dysarthria are present. Some patients are unable to speak or utter a sound, though they show no evidence of paral3^sis of the peripheral mechanism of speech and are able to show in some way that they are conscious and have normal understanding. In other words there is a motor aphasia. STUDIES OF SELECTED CASES 95 There are certain other findings that are probably pro- duced by cortical lesions. These are spastic monoplegias which are frequently preceded by pain and hyper- sesthesia. One patient observed at the Presbj'terian Hospital, and reported in Part I (p. 20), had as her Fig. 13. — Accumulation of Ameboid Glia Cells in the Internal Capsule. initial symptom pain in the index finger of the right hand, which rapidly spread to the whole arm, and on disappearing left a partial monoplegia. Sensory disturbances are as a rule very slight. At the beginning of the illness, as noted before, there are fre- 96 EPIDEMIC ENCEPHALITIS quently generalized pains. The pains may be localized, however, and be associated with hyperaesthesia. Hyper- aesthesias in portions of the surface supplied by the fifth nerve are described but are infrequent. The cranial nerve palsies are frequently bilateral, almost always incomplete and may be transient or variable. Mental Symptoms. Any of the three cardinal symp- toms given by Netter, namely, lethargy, fever, and cranial nerve palsies, may be absent; but the one most frequently present is probably somnolence, stupor or lethargy. At the onset of the illness the mental symptoms are fre- quently irritative, and delirium with hallucinations and tlelusions is often noted. This is more apt to occur at night and may be present when in the day time the mental state is that of stupor with normal rationalit^^ The onset of the drowsiness is usually some days after the first sj^mptoms have appeared. At first it is simply a drowsi- ness with a constant desire to sleep. In a few daj^s there is more pronounced somnolence and lethargy. The pa- tient may as a rule be aroused easily when apparently in deep stupor and when aroused show a normal intel- lectuality, being well oriented, having a good memory, and often showing a surprising keenness of perception and realization of what is taking place about him. Some of the patients show a marked degree of jocularity, turn- ing everything to joke or witticism. Frequently there is a striking absence of the appreciation of the seriousness of their condition, and an entire lack of anxiety or fear as to the eventual outcome of their illness. In some instances, especially in the abortive type, there is no lethargy and merely a tendency to somnolence from which they are easily aroused. For some reason which is difficult to explain, the groups which are classed as the STUDIES OF SELECTED CASES 97 Fk;. 14. — Internal Cap,sul( . JJi 98 EPIDEMIC ENCEPHALITIS paralysis agitans type are less apt to have deep lasting stupor than are the other varieties. There is generally a lack of spontaneity and initiative. The patients rarely speak except in answer to direct questions. They are acutely aware of pain on catheterization and of dis- comfort when the bed is wet with urine. However, they may not ask to have their bladder or rectal functions relieved. Fever. A moderate degree of fever is usually present at the onset. It generally ranges from 100 to 102 degrees, and may be associated with chilly sensations but rarely a shaking chill. The initial fever usually continues but a few days, and then entirely or nearly disappears. In some of the severe and fatal cases, after a varying period (often several weeks) it gradually rises again, associated with rapid respiration and increased pulse rate, until it reaches 106 or 107 degrees. This is a very ominous sign and usually precedes a fatal termination. On the other hand, there may be practically no fever during the en- tire course of the illness even if it ends fatally. This is especially true in the group where the brain stem is the portion mainly involved (Case V). Ocular Symptoms. Manifestations due to interference with the oculomotor apparatus have been present in 53 per cent of the reported cases. The onset of the ocular symptoms is usually coincident with the drowsiness, but may be the first symptom, or may not occur until several weeks after the inception. Ptosis is one of the most fre- quent manifestations. It is rather unusual in appearance, resembling that seen in hysteria or myasthenia gravis, being partial and without attempted compensation on the part of the patient by raising the corresponding e^yelirow. At times there is no ptosis but the eyes are STUDIES OF SELECTED CASES 99 B&'^V'*' ' \S Fig. 15. — Intinual Ciipsule Showing Advi'iitituii l>yiiii)h ^i)ace Infiltration. 100 EPIDEMIC ENCEPHALITIS kept partially closed on account of photophobia. Stell- wag's sign, or infrequent winking, is often present when there is a stupor or lethargy. One patient was observed four and a half minutes before winking occurred. Markedly varying forms of ocular palsies are found, A complete third or sixth nerve paralysis, such as is com- monly produced! ^^ syphilis, is infrequently observed. There is rarely a simple internal or external ophthal- moplegia, the findings being usually a partial combination of the two. The picture usually points to nuclear or supra- nuclear lesions. Conjugate deviation and limitation of the voluntary movement of the eyes in a horizontal or vertical plane may be present. In Case II, Part II, there was a slight conjugate deviation upward and an in- ability to look downward. For a short period another patient (Case V) showed limited lateral movement to either side, while there was an inability to converge or to look either up or down. Nystagmus or nystagmoid movements are frequently seen. In the patients the writer has observed there has been more of a slight rhythmic nystagmoid movement on contraction of a paresed muscle than a distinct nystagmus. Paralysis of accommodation with normal pupillary reaction may occur as in botulism or post-diphtheritic paralysis. It may be bilateral and the onlj^ evidence of ocular involvement. The findings in any given case frequently cannot be assigned to lesions of any particular neuromuscular group, but can only be explained on a basis of incomplete involvement of several elements of the oculomotor nuclei. Moderate degrees of swelling of the disc are found commonly, but never the severer grades of choked STUDIES OF SELECTED CASES 101 it Fig. 16. — Internal Capsule, Showing Adventitial Lj'mph Space Infiltration. 102 EPIDEMIC ENCEPHALITIS disc. Photophobia is frequently present but is usually not severe. The ocular findings which are more or less char- acteristic of this condition may be summarized as follows: > ,< -M-^':^^^ m Fig. 17. — Medulla. Hemorrhage, Infiltration and Vascular Changes in Substantia Reticularis Grisea. 1 . There is rarely clear-cut complete paralysis of anj^ one oculomotor nerve. 2. The disturbances are very frequently bilateral. STUDIES OF SELECTED CASES 103 3. The paresis is usually partial and involves more than one or only part of one neuromuscular group. 4. Ptosis is the most common isolated ocular finding. It is partial and uncompensated by contraction of the frontalis. Fig. 18. — Medulla. Localized Cellular lufiltiatioii ul' Furinatio Reticularis Grisea, 5, Unilateral or bilateral paralysis of accommodation, dissociated from pupillary involvement, may occur. 6. The ocular jxalsios are frequently not stationary having a tendency to alteration, in some instances even from day to day. 104 EPIDEMIC ENCEPHALITIS 7. Lesions of the fundus are usually absent, but there may be a slight degree of papilledema. BLOOD EXAMINATION The blood count does not show constant alteration, though there is usually a moderate leucocytosis. Vaidya''^ reports observations in twenty cases. The highest count in his series was 14,000, and the lowest 4,000, with an average of 8,000 to 9,000. The differential count showed approximately normal proportions. In twelve cases of this series in which blood examina- tions have been made the lowest was 7,700 and the highest 29,700, the average count being about 15,000. The differential count showed no constant variation from the normal. The Wassermann reaction is negative, and the blood cultures sterile. SPINAL FLUID In the great proportion of cases reported the spinal fluid has been normal. Some observers report increased cells counts and globulin in every case, while others have never seen any abnormalities. The pressure may be normal, but it is frequently in- creased. This is usual in the early stages of the disease, while later on it is normal or occasionally decreased, as has been observed several times shortly before death. The appearance has in all cases been perfectly clear and colorless, except for one case reported by Wilson, where one puncture gave fluid which was slightly yellowish and was probably due to hemorrhages into the lepto- meninges. Subsequent spinal puncture in this case gave a clear colorless fluid. Globulin is usually absent but may be reported as plus STUDIES OF SELECTED CASES 105 or minus or present only in the minutest trace. Where there is a pleocytosis it is frequently present. The cell count is generally normal but is increased in a minor proportion of cases. The cells are small lympho- cytes and if increased are usually only moderately so, -iA^ **v 'v; •*■ M^' ',( '• '■ m "•>'. Fig. 19.— Medulla. Diffuse Infiltration. the cell counts showing 10 to 30 cells per cubic milH- meter; but counts of 200 cells and over have been reported. The Wassermann reaction is negative in all dilutions. Cultures are sterile. Organisms have been cultivated lOG EPIDEMIC ENCEPHALITIS from the spinal fluid in isolated cases, but never con- stantly, and they have been considered contaminations. The colloidal gold curve in the few cases in which it has been examined is usually negative. Case X of this series had a trace of globulin, 23 cells, and a gold Fig. 20.— ^Medulla. Ac.uti; Cloudy Swelling in the Cells of the Nucleus Ambiguus. curve of the meningitic type (122 343210 0). Fehling's solution always shows a normal reduction. It seems logical to suppose that the changes in the spinal fluid are present in the cases in wliich there is STUDIES OF SELECTED CASES 107 cortical hemorrhage or meningeal inflammation. As this is very slight or absent in the majority of instances, the spinal fluiil would be expected to show no pathological alterations. Fig. 21. — Medulla. Formatio Reticularis Grisea. Fat Pig- mentary Degeneration of One of the Nerve Cells. PROGNOSIS At the present time, as our knowledge of epidemic encephalitis is based on but a few months' observation and study, it is impossible to obtain accurate data or give reliable statistics as to the termination of this disease. 108 EPIDEMIC ENCEPHALITIS Fig. 22. — Cortical White Matter. Occipital Lobe. Localized Accumulations of Ameboid Neuroglia Cells. STUDIES OF SELECTED CASES 109 In discussing the prognosis we must consider it not only as to life, but also as to completeness of restitution. The mortality as given by different observers varies considerably, as may be seen from the following statistics : NO. OF CASES FATAL Economo 11 6 Netter 15 7 VonWiesner 13 2 Findlay 3 1 Wilson, K 13 2 Tilney and Riley"" 20 6 Hall 16 Abrahamson' 52 5* Total 143 29 In 113 cases reported in the literature in which the condition at the time of writing or the termination was given, and including those pei'sonally observed, the statistics are as follows: CASES PER CENT Fatal 35 30.9 Recovered 29 25 . 6 Improved 37 32 . 7 Stationary 12 10.6 The prognosis at the time of onset in all cases .should be guarded. While the termination in any one type may be fatal, some varieties generally have a more hopeful outlook than others. The group with general symptoms but without any localizing signs has a mortality which is in direct relation to the intensity and duration of the lethargy. This group as a whole has a rather grave out- look, although many of the milder cases completely re- cover. The occurrence of increasing temperature, pulse and respiratory rates is very ominous, death following in a * "About 10 per cent" of 52 cases. no EPIDEMIC ENCEPHALITIS week or ten days. Acute delirium or continued irrational- ity are unfavorable. The paralysis agitans type has a Fig. 23. — Chromatolysis and Acute Cloudy Swelling in the Cells of the Anterior Horns of the Spinal Cord. tendency to slow development and long duration. It is probable that in some of the milder forms complete STUDIES OF SELECTED CASES 111 ^ ■■1 *;'> V. h. ■ ll Hm^^^H • V « '♦ ♦'/# SBiJ^^BB^Bi^^B ' , .f-^'- ■ .y'S' IW' ' 1 " ..';/..'"/■; ' ^ ;/ ■ '"'^>:-:''S ■ f. 'V. /.. . 'v •■^:-^/v ""^V- .■>?^(i::V s '• "■ A 'm -''■'-"" S •' J^" i 1 ^ A I^C' 1 * * ' ^ '4 ' '"m r 'i'^l •' ' • . •'. ? ' , • , ' ' { jM^ ' -^ ■../ 'J. "- f l\ ' " %' , ■. ■ ■ / - .. \yS^' • ' vl , p- ^ * ^0 • " ' ''. ^ ' » ^ , f ', , ' ' • %!^- **' ' * / .* '* *• •' . '\ . i 'v ' ., . ' '^'' ' .*\ r ■'>■'. c " ■ -y' r- - ' ' -«» sp'_ .f , '4 . tfjMi 4 f^ '*,'<* 1 '. ' ^, .' . A* ■' ' ■ ' • ^ > gg ■B W' Fig. 24. — Blood Vessel Showing \ iiclio\\-i{()i)iii .^pncc Packed with Lymphocytes. 112 EPIDEMIC ENCEPHALITIS restitution does occur, but it is too early to tell what amount of restitution takes place in the severer cases which survive. The outcome of cases with evidence of severe lesions in the pyramidal tracts is also uncertain, but transient weakness, ankle clonus and positive Babinski reflexes have been observed. The greater proportion of the brain stem type recover, though complete restitution may be protracted. The ocular palsies are subject to variation and improve more rapidly than do lesions of the facial nerve. Any of the symptoms may be aggravated by fatigue and in this way may reappear after recovery has taken place. CHAPTER XVII CASE REPORT I Mrs. M. B. H. Aged fifty-one; married. Housewife. Chief Comylaint. General weakness for four months, dizziness for thirteen days. Family History. Father died at eight3^-five; cause unknown. Mother died at seventy-nine of cancer of the breast. One sister died at eighty-four of cerebral hemorrhage. No history of rheumatism, heart disease, tuberculosis or insanity. Personal History. Patient has been married twenty- six years; husband is living and well. She has had three children who are living and well, and three miscarriages. Her habits are good; she has never used alcohol or drugs. There has been no recent change in weight which is 140 pounds. Past History. Scarlet fever at nine, but without complications. Pleurisy and pneumonia fourteen years ago. No operations or injuries. Head: Occasional headaches for several years attrib- uted to weak eyes. Eyes: Has worn glasses for thirty-five years for astigmatism and hypermetropia. Ears and Nose: Negative. Mouth and Throat: Negative. Respiratory: Fourteen years ago had "pneumonia and pleurisy." This illness was short. There was no pain at that time, no cough, no hemoptysis. Heart: Has never had palpitation, dyspnea or swelling of the feet. 113 114 EPIDEMIC ENCEPHALITIS Gastrointestinal: Appetite is good as a rule. Has had occasional slight distress in epigastrium after meals with some gaseous eructations, but never vomiting. Bowels: Always irregular and constipated. Constipa- tion relieved by daily enemata. Has had slight external hemorrhoids for the past four years; no bleeding. Urinary: Occasional nocturia; no frequency; no dysuria nor hematuria. Menstrual: Periods began at the age of thirteen and were always regular. No dysmenorrhea or met- rorrhagia. Menopause began two and a half years ago. Periods ceased last April. Since that time there has been a slight white vaginal discharge. Extremities: No tremor nor deformities. Occasional numbness in the hands. Present Illness. About four months ago the patient noticed that she could not do her housework without becoming exhausted. About three months ago she had a severe head cold characterized by profuse waterj^ nasal discharge, headache, and slight generalized pains. This continued for about two weeks and then gradually cleared up. There was no fever, sore throat, cough or expectoration. She is not at all subject to colds, this being the first one she had had in over three years. The general weakness has gradually increased but until recently was accompanied by no other symptoms. Thirteen days ago she became dizzy and could not stand up. She went to bed and became drowsy, taking little interest in what was going on around her. About this time she lost her appetite. She has had no pain, no epigas- tric distress, vomiting or fever. Her main complaints at present are generalized weakness, loss of appetite, slight headache, vertigo and inability to get in a com- fortable position in hcd. Her husband states that she STUDIES OF SELECTED CASES 115 has always been of an exceedingly bright and cheerful disposition, while now she has gradually developed a staring expression and a tendency to be drowsy and quiet. Ther(; have been no other mental changes. PHYSICAL examination: OCTOBER 27, 1919 General Appearaiice. A drowsy, unresponsive woman lying quietly in bed, with a vacant expression, eyes partially closed and staring directly forward, apparently in no distress. She is rather easily aroused, and when so speaks in a slow, faint, monotonous, high-pitched voice. She complains of extreme distress in all portions of her body especially below the waist, saying that it is impos- sible to get in a comfortable position and that she has been constantly turning in bed but is unable to find any position in which she can get relief. She also states that she is drowsy and lacks her usual alertness and vivacity. Although the patient says that she has been constantly moving in bed, she was observed for some time before she was aroused, and during this time she made no mus- cular movement of any kind, even winking only once in four or five minutes. Skin is slightly pale, dry and warm. Hair distribution is of the normal female type. Head: There is no sinus tenderness or deformity. Ears: Brums are normal; there is no mastoid tenderness. Eyes: The lids are drooping, giving the appearance of double ptosis, though she is able to open them fully. There is a slight external strabismus of the right eye. The conjunctivae are a little pale. The eye grounds show the vessels clear. The margins of the discs are sliglitly 116 EPIDEMIC ENCEPHALITIS hazy but there is no real choked disc. The vessels in the retina are normal. Nose is normal; no discharge. Mouth: The teeth are in good condition. The breath is foul. There is slight pyorrhea. The tongue is coated. The tonsils are large with some exudate in the mouths of the tonsillar crypts. The pharynx is slightly congested. On smiling the mouth is drawn slightly to the right. The whistling sound is normal. Neck is slightly stiff but there is no distinct rigidity. Superficial lymph nodes are not enlarged. Thyroid is not palpable. There are no visible pulsations. Thorax is well developed and the breasts are soft. There are no masses. Heart is slightly rapid; regular; pulses equal and of good quality. The cardiac outline is normal; the first sound at the apex is rather sharp and snapping. There are no murmurs, no accentuation of the aortic second sound. Pulse rate is 98. Blood pressure is 110-80. Lungs are clear and resonant throughout. Abdomen is soft and slightly obese. No tenderness or rigidity. The liver and spleen are not palpable. No signs of free fluid. Extremities: No edema or deformity. Vaginal Examination: Introitus easily admits two fingers. The cervix is in the midline, well back, freely movable. There is a slight horizontal laceration. In the right fornix close beside the uterus there is a firm, slightly tender mass that can be easily felt between the two hands. NEUROLOGICAL EXAMINATION.' OCTOBER 29, 1919 Voluntary Motor System. Abnormal Attitudes and Deformities. The attitude is described above. STUDIES OF SELECTED CASES 117 Gait. The patient walks slowly, deliberately and rather stiffly, the feet lifted but slightly from the floor. Coordination. Equilibratory. Standing with feet to- gether, eyes open, there is slight irregular swaying which is not accentuated by closing the eyes. Non-equihbratory. Finger-to-nose, pointing and past- pointing tests show no deviation, though the movements are slow, stiff and with a moderate tremor. There is no dysmetria or adiadochokinesis. Skilled acts. There is no dyspraxia. The patient is able to feed herself and arrange her hair. Speech. There is no aphasia or dysarthria, though the speech is slow, weak and in a rather high-pitched monotone. Reflexes: Deep Right Left Jaw 2 2 Biceps 2 2 Triceps 2 2 Radial 2 2 Ulnar 2 2 Suprapatellar 2 2 Patellar 3 3 Achilles 1 1 Superficial Ciliosi^inal Present Present Supra-umbilical 2 2 Suprapubic 2 2 Upper lateral abdominal 2 2 Lower lateral abdominal 2 2 Plantar flexion Babinski and modifications 1 = slight 2 = active 3 = very active 4 = with transient clonus 5 = with permanent clonus 118 EPIDEMIC ENCEPHALITIS Ahnor7nal Involuntary Movements. On voluntary movement there is a slight but distinct tremor of the hands. No other tremors, twitchings, athetoses, chorei- form movements or spasms. Muscle Strength. The patient is able to sit up in bed and to rise from the recumbent to the standing position. Opposed and unopposed movements of the neck, shoul- ders, arms, forearms, hands, fingers, thighs, legs, feet and toes show only a moderate general weakness. Muscle Status. Contour and consistency normal. There is a general moderate hypotonia with resistance to passive movement, with a slight, irregular cog-wheel release. Abnormal Associated Movements. Not tested. Nerve Status. No observation. General Sensory. There is no disturbance of touch, pain, temperature, vibratory, pressure, muscle tendon sense or stereognostic perception. Cranial Nerves and Head. Olfactory Nerve and Nose. The sense of smell is normal on each side. Oculomotor Apparatus. Visual acuity seems normal. Perimetry, tested by the finger method, is normal. Eyegrounds: There is very slight haziness of the periphery of the discs in each eye. The pupils each measure 3 millimeters. The}^ are circular, in the center of the iris, and regular. They react normally to light and on accommodation. The lids are partially closed, the palpebral fissures measuring 7 millimeters. The lids may be, fully retracted, however, showing a thin white line of sclera above the cornea. There is no exophthalmos, enophthalmos or ptosis. The patient complains of photo- phobia and gives that as the reason for partially closing her eyes. There is no strabismus or other ocular devia- tion. The slight external stral)ismus noted two days ago STUDIES OF SELECTED CASES 110 in the general physical examination has disappeared. There is no nystagmus and the conjugated eye move- ments are normal. Acoustic Nerve and Ear. A watch is heard 6 inches from the right ear and 83'2 inches from the left. Trigeminus Nen;e and Mouth. Voluntary movements of the jaw are normal in all directions. The corneal reflexes are normal, and there is no abnormality of sensation in the fifth nerve area. Facial Nerve and Face. Taste on the anterior two- thirds of the tongue is normal. There is a slight flattening of the lower portion of the face on the left side and diminished movement of the left corner of the mouth on speaking. Slight weakness is also evidenced on showing the teeth. There is no weakness of the upper face on either side. Secretion of tears and saliva are normal. Glossopharyngeus and. Vagits Nerves, Pharynx and Larynx. The uvula is in the midline. Palatal and pharangeal reflexes are normal. Swallowing, respiratory and cardiac action are normal. Spinal Accessory Nerve. There is no paralysis of either sternomastoid or trapezius muscle. Hypoglossal Nerve and Tongue. The tongue is pro- truded in the midline and can be moved normally in all directions. LABORATORY EXAMINATIONS AND CLINICAL NOTES Blood Wassermann: October 27, 1919 Alcohol antigen Negative Cholesterin antigen Negative Blood Count: October 27, 1919 Red blood cells 5,200,000 Hemoglobin 70 per cent. White l)lood cells S,GOO 120 EPIDEMIC ENCEPHALITIS Polymorphonuclear leucocytes . . 75 per cent. Large lymphocytes 10 per cent. Small lymphocytes 12 per cent. Transitionals 3 per cent. Morphology of red cells Normal Urine Examination: October 27, 1919 ^ Specific gravity 1 . 025 Reaction Acid Color Yellow Turbidity Slight flocculent precipitate Albumin Very faint trace Sugar None ,,. . , . ,. f Few squamous epithelial cells Microscopical examination, i „ i •, i i . n [ l^ew white blood cells Spinal Puncture: October 28, 1919 Amount 10 c.c. Pressure Normal Appearance Clear, colorless Globulin + Cells 43 lymphocytes Wassermann 2 c.c. 1 c.c. .6 c.c. .2 c.c. Alcohol antigen Neg. Neg. Neg. Neg. Cholesterin antigen . . . Neg. Neg. Neg. Neg. Eye Examination: November 4, 1919 {Dr. Schoenberg). There is a slight defect of convergence as shown by diplopia on looking at near objects. The upper, temporal and lower margins of the right disc are indistinct. The same is true of the left disc, only that the condition is a little more pronounced. Both discs give one the impres- sion of a mild optic neuritis. There is no ptosis or evidence of any other paralysis. November 10, 1919. The mental attitude has bright- ened remarkably; she is apparently quite normal. Her main trouble now is constipation and gas in the stomach. STUDIES OF SELECTED CASES 121 November 16, 1919. Physical examination reveals none of the pathological findings formerly present. The lids do not droop. The face is more mobile, the voice less monotonous. There is no catatonia or spasticity. The patient can get comfortable in bed. The gait is normal. The chief complaint now is indigestion, loss of appe- tite, and gas which seems to be dependent upon her constipation. Temperature while in the hospital ranged from 98° to 100°; -pulse 90 to 130; respirations 18 to 24. SUMMARY The patient complained of general weakness for four months and dizziness for thirteen daj^s following what appeared to be a nasopharyngitis. There was spasticity, general slowing down of all movements, mask-like face, monotonous voice, catatonia, photophobia, and a mild grade of optic neuritis. The spinal fluid showed a positive globulin reaction and 43 cells with a negative Wasser- mann. The spasticity and mask-like appearance cleared up rapidly and the mental attitude became much brighter. Constipation and gastric distress were the chief com- plaints at the last and all signs of encephalitis had dis- appeared. CHAPTER XVIII CASE REPORT II Miss. M. K. Aged seventeen. Single. Stenographer. Family History. She is an onl}' child. Father died of heart disease; mother is living and well. Past History. Patient has had the ordinary diseases of childhood, but no accidents, injuries or operations. She was well previous to the onset of the present illness. Present Ulness. On September 13, 1919, the patient noted that she had a slight cold in the head. The next day there was a thin, watery nasal discharge, headache, pains in the back and limbs, and a fever of 102 degrees. That night she had difficulty in sleeping and was slightly delirious. The next two days her condition was practic- ally the same except that her pain and headache were more severe and she had constant profuse perspiration and general weakness. On the fifth day she commenced to feel drowsy, and the pain, nasal discharge and dis- comfort were less. The sixth day double ptosis appeared and the drowsiness was more marked. The headache had entirely disappeared by this time and the coryza was much improved, the stupor and ptosis dominating the picture. At this time her muscles became very rigid and there was a marked resistance to passive movement. During the next few daj's the drowsiness deepened to lethargy which continued until the present. NEUROLOGICAL EXAMINATION: SEPTEMBER 27, 1919 The patient is lying in a supine position, her mouth and eyes are closed, arms folded across her chest, fingers 122 STUDIES OF SELECTED CASES 123 flexed. There is a slight flexion of the thigh and leg. The face is expressionless and the patient has the appear- ance of one in a normal, deep sleep. Voluntary Motor System. Abnormal Attitudes and Deformities. None present. Gait. The patient is unable to stand or walk. Coordination. Finger-to-nose and heel-to-knee tests are performed slowly and stiffly and with some tremor. Normal precision in every case. There is no adiado- chokinesis. Skilled Acts. There is no dyspraxia or aphasia. Speech is slow and monotonous and scarcely more than a whisper. Reflexes: Deep Right Left Jaw 3 3 Pectoral 2 2 Biceps 3 3 Triceps 3 3 Radial 3 3 Ulnar 3 3 Suprapatellar 3 3 Patellar 3 3 Achilles 3 3 Superficial Ciliospinal Present Present Supra-umbilical Present Present Suprapubic Present Present Upper lateral abdominal Present Present Lower lateral abdominal Present Present Plantar flexion Present Present Babinski and modifications Absent Absent Abnormal Involuntary Movements. There are no tremors, twitchings, choi'eiform or athetoid movements except on voluntarj' exertion, such as touching the nose 124 EPIDEMIC ENCEPHALITIS with the finger, when there is a rather coarse tremor of the whole extremity. Muscle Strength. The patient is unable to rise from the recmnbent to the sitting position. All the movements of her extremities are very weak, but are equal on the two sides. Muscle Status. There is a marked hypertonic condi- tion of the general musculature giving rise to a marked spasticity. The arms and legs will be held in a position in which they are passively placed if it requires no muscular effort to retain them in that position. Ahnormal Associated Movements. Not tested. Nerve Status. No observation. General Sensory. Examination difficult and inac- curate because of the incooperation of the patient. However, touch, pain, temperature and pressure senses seem normal. Cranial Nerves and Head. Olfactory Nerve and N^ose. Sense of smell not tested. Optic and Oculomotor Apparatus. Visual acuity in each eye is normal. Perimetry, roughly tested, shows no field contraction. Eyegrounds are normal, discs well outlined, no papillo-edema. Pupils are in mid-dilatation, regular and equal. They react actively to light and on accommodation. The eyes are closed but can be opened to about half the normal extent, the right shghtly less, however, than the left. There is no exophthalmos or enophthalmos. There is a moderate external strabismus in the right eye, which, however, is said to be congenital. Conjugated eye movements: Motihty is good up, to the right and left, but there seems to be an inability to look down. There is no nystagmus. Trigeminus Nerve and Mouth. The movements of the jaw are equal and normal in all directions. The jaw reflexes are active, the corneal reflexes present. STUDIES OF SELECTED CASES 125 Acoustic Nerve and Ear. Hearing is normal on each side. Facial Nerve and Face. There is no facial weakness or paralysis on either side. Glossopharyngeus and Vagus Nerves, Pharynx and Larynx. The uvula is in the midline. Palatal and pharyngeal reflexes are normal. Swallowing and respira- tion are also normal. Spinal Accessory Nerve. No evidence of paralysis of either sternomastoid or trapezius muscle. Hypoglossus Nerve and To7igue. The tongue is pro- truded in the midline and its movements are equal in all directions. Mental Status. The patient seems alert to all that is going on about her. She rarely speaks unless aroused and then usually only in answer to direct ques- tions. She worries somewhat about her work and to a less extent about her own condition, but has no somatic complaints. General Physical Examination is practically nega- tive. The heart and lungs are normal. The liver and spleen are not palpable. There is generally a slight ab- dominal distension. Sweating is profuse. There are no enlarged lymph nodes. The thyroid is not palpable. Spinal Puncture: September 28, 1919 Appearance Perfectly clear Pressure Normal Cells 5 lymphocytes Globulin Negative Fehling Normal reduction Clinical Notes. Patient's eyes were closed most of the time but she was able to open them to about one half of the normal extent. If there was light in the room she 126 EPIDEMIC ENCEPHALITIS would always keep them closed; but if the gas were turned down she would almost always open them. If they were closed and the light from a pocket flash- light suddenly flashed on them, the lids would be closed more tightly. There was a slight external strabismus of the right eye, but this had been present since childhood. During the second week of her illness there developed an inability to look downward, though she could turn the eyes upward and move them laterally. The pupillary reflexes were active throughout the entire course of her illness. Her mental state was practically the same as it had been before the illness commenced. There was at no time any tendency to joke, laugh or smile which is so marked in some patients with this disease. At all times she seemed particularly alert to everything that was going on about her. She would hear knocks at the door that were not heard by her mother or the nurse, and would tell them to open the door. Usually she would not speak spontaneously or ask for anything, but if she were aroused she would talk and would show that she was cognizant of the happenings about her. She would never volunteer information that she desired to empty her bladder or bowel, and occasionally passed her urine involuntarily, but being aroused at regular intervals she was able to evacuate both bladder and bowel normally. There was no voluntary attempt made to move and after remaining in one position for a long time; if aroused she would ask to be moved but would make no effort to move herself. If asked to move her arms or limbs she would do so, but the movements were slow and trembling. There was no real paralysis of any part. During the first three weeks of her illness there was a pronounced increase in the muscle tone which gave rise to a general STUDIES OF SELECTED CASES 127 rigidity, but there was no tendency to hold the limbs in any position in which they were placed if this required any muscular effort. In the third week of her illness there were two short convulsions which consisted of a tightening of the jaw, Fig. 25.— Case 11. Temperature and Pulse Chart During Final Week of Illness. Temperature Pulse a spasm of the respiratory muscles and general tonic contractions of the musculature. In the sixth week the temperature rose from between 99° and 100°, which was the level it had been maintaining since the drowsiness had come on, to 103° and 104°. The pulse increased from between 90 and 100 to between 120 and 150, and respirations from 18-22 to 80-50. 128 EPIDEMIC ENCEPHALITIS At one time the respirations were 60, the temperature 107 and the heart rate 185. (The pulse could not be counted at the wrist.) At about the same time the spasticity became much less marked and it was more difficult to arouse the patient; but when aroused, she seemed to understand what was said to her though she made no effort to speak. On the 42nd day of her illness she died from respiratory paralysis. SUMMARY The illness commenced with symptoms similar to those of influenza, with restlessness and delirium. Soon these gave way to somnolence and lethargy which con- tinued until the end, and dominated the clinical picture. The main findings on neurological examination, outside of the mental state, were general muscular spasticity, double ptosis, and an inability to look downward. The course was practically stationary until a week before death, when there was greater stupor, increasing pulse, respiratory rate and temperature, with decided lessening of the general rigidity. CHAPTER XIX CASE REPORT III Mr. G. A. D., Aged twenty-nine, Married. Chauffeur. Admitted to the hospital November 9, 1919. Chief Complaints. General weakness for three weeks; blurring of vision for two and a half weeks. Family History. Both parents are living and well. One brother and three sisters are also living and well. One brother died of lobar pneumonia. No history of tuberculosis, rheumatism, heart trouble or Bright's disease in the family. Personal History. Patient was born in the United States and has been married three years. His wife and two children are living and well. The last pregnancy resulted in miscarriage the cause of which is unknown. He eats regularly; takes an occasional glass of beer or whiskey but never in excess, smokes twenty cigarettes a day. His occupation is that of an automobile repair man. He has been working at night for the past six weeks. The average weight is 187 pounds; he has lost 25 pounds since the onset of the present illness. Previous History. No acute infectious diseases. Ampu- tation of the ring finger of the right hand several years ago. Head: No headaches. Eyes: Vision was entirely normal up to the present illness. Occasionally on rising suddenly after stooping, he has had an attack of dizziness in which "everything 129 130 EPIDEMIC ENCEPHALITIS gets black." This continues for only a minute or two. He has had about twelve of these attacks during the past nine years. Nose: Negative. Throat: Negative. Teeth : Always in good condition. Respiratory : Is not subject to colds. Cardiac: No dyspnea on exertion; no swelling of the feet. Gastrointestinal: Appetite good. No constipation until the present illness. Never jaundiced. Geriito-Urinary : No nocturia. Gonorrhoea twice, in 1908 and 1909. Syphilis denied by name and symptom. N euro-Muscular: Negative prior to the present illness. Present Illness. The onset occurred three weeks ago in the form of chilly sensations followed by fever. He would have three or four chills a day followed each time by a rise in temperature. The chills would be slight and last about three-quarters of an hour, while the fever continued for one or two hours. He was given quinine and whiskey but without relief. About two weeks ago he developed general weakness and lassitude and at the same time had insomnia which is still present. He says he does not sleep either during the day or at night. Two weeks ago he noticed blurring of vision on attempting to read. This got rapidly worse until the present when he is unable to read even the largest headlines in the newspaper. Far vision, however, is normal. There has been no diplopia nor headache. Con- stipation has been present since the onset. There is no muscle twitching nor photophobia. Physical Examination. General Appearance is that of a well nourished, well developed young adult man lying stiffly in bed, appearing neither acutely nor chron- STUDIES OF SELECTED CASES 131 ically ill. His expression is mask-like. His movements are few and slow. Skin is dry, coarse and cool. Superficial lymph nodes not palpably enlarged. Head is oblong-shape, prominent square chin. Case III. Eyes: Conjunctivae are slightly congested. There is a slight twitching of both eyelids. No strabismus or nystag- mus. Eyegrounds: The nasal side in both optic discs is hazy, the right slightly more marked than the left. The fundi are otherwise normal. Ear-drums are normal; there is no mastoid tenderness. Nose: Negative. 132 EPIDEMIC ENCEPHALITIS Mouth: Buccal mucosa negative. The tongue is a grajdsh-brown, covered with a thick, dry coat. Teeth are well preserved. The gums show beginning pyorrhea. Throat is slightly congested. Tonsils are small and not diseased. Neck: There is slight limitation of extreme flexion. No pronounced rigidity. Chest is well developed; expansion good and equal on both sides. Lungs: There is slight relative dullness over the sec- ond and third left interspaces; otherwise the lungs are clear throughout except for a few rales at the right base which disappear after coughing. Heart is normal in outline. The sounds are of good quality; action is regular; no murmurs. The pulse is 64, regular and full; the vessel wall is not palpable. Blood pressure 120-75. Abdomen is markedly retracted with considerable vol- untary spasm. No viscera or masses felt. External Genitalia: Negative. Rectal Examination: The prostate is small and smooth. No masses. Extremities: Movements are slow with diminished strength. The third finger of the right hand is missing. NEUROLOGICAL EXAMINATION: NOVEMBER 13, 1919 General Appearance. The patient is lying dorsally in bed with his arms crossed on his chest. His eyelids are partially closed, the eyes directed forward with a fixed, emotionless stare. The mouth is symmetrical and held partially open. There is a waxy, death-like appearance of the entire face. He is easily aroused and when so speaks rather slowly, but answers all questions clearly and gives no evidence of lack of intelligence or defective cerebra- STUDIES OF SELECTED CASES 133 tion. If he is left alone and his attention is not centered on what is going on about him, he rapidly sinks back into liis previous apathetic state. Voluntary Motor System. He is able to stand and walk. The movements are a little slow and unsteady, but the difficulty seems to be due to weakness rather than to incoordination. Standing with his feet together he swaj^s slightly but not more so when his eyes are closed. Finger-to-nose, heel-to-knee, pointing and past pointing tests are accurately though not rapidly per- formed. Dysmetria and adiadochokinesis are absent. Skilled Acts. There ia no dyspraxia, dysarthia or aphasia. His voice is rather slow, soft, and without much inflection. Reflexes: Deep Right Left Jaw 2 2 Pectoral 2 2 Biceps 2 2 Triceps 2 2 Wrist 2 2 Radial 2 2 Ulnar ■... 2 2 Suprapatellar 1 1 Patellar 2 2 Achilles 2 2 Superficial Supra-uin1>ilical 2 Suprapubic 2 Upper lateral abdominal 2 Lower lateral abdominal 2 Cremasteric 2 2 Plantar flexion 2 2 Bal)inski and modifications Abnormal Involuntary Movements. There are no tre- mors, twitchings, spasmodic movements or convulsions. Muscle Strength. He is able to rise from the recumbent position to sitting or standing. Flexion, extension and 134 EPIDEMIC ENCEPHALITIS rotation of the trunk and extremities show average strength everywhere. Symmetrical movements are equal. Muscle Status. Contour and consistency are normal. There is slight but general hypertonia with some resist- ance to passive movement but no suggestion of irregular cog-wheel release. General Sensory. Touch, pain, vibratory, pressure, muscle tendon sense and stereognostic perception are normal. Cranial Nerves and Head. Olfactory Nerve and Nose. Sense of smell is normal in each nostril. Optic and Oculomotor Apparatus. Vision is normal for distance. Objects more than 10 or 15 feet away are seen perfectly distinctly, but there is no ability to accom- modate, so that near objects are blurred and indistinct. Perimetry, with the finger test, is normal. Eyegrounds show a very slight haziness of the nasal side of the disc in each eye, but no hemorrhages or other abnormality. Pupils: The right pupil is larger than the left, being 6 millimeters, while the left is 4 millimeters in diameter. There is no eccentricity or irregularity. Both react to light and on convergence. Palpebral fissures: Occasionally the right appears larger than the left, but at other times they are equal. There is certainly very little difi'erence. There is no ex- ophthalmos, enophthalmos or ptosis. There is no stra- bismus, other ocular devation or nystagmus. Acoustic Nerve and Ear. Hearing is normal in each ear. Trigeminus Nerve and Mouth. There are no sensory disturbances and movements of the jaw are normal in all directions. Facial Nerve and Face. There is no evident weakness STUDIES OF SELECTED CASES 135 of either upper or lower branches of the facial nerve on either side. Glossopharyngeus and Vagus Nerves, Pharynx and Larynx. The uvula is in the midline. The palatal re- flexes and pharyngeal reflex are normal. Swallowing is performed without difficulty. , Spinal Accessory Nerve. Movements of the sterno- mastoid and trapezius muscles are normal and equal on the two sides. Hypoglossus Nerve and Tongue. The tongue is pro- truded in the midline; its movements are normal in all directions and there is no tremor. LABORATORY EXAMINATIONS AND CLINICAL NOTES Blood Count: November 11, 1919. Red blood cells 5,000,000 Hemoglobin 7.5 per cent. White blood cells 8,000 Polymorphonuclear leucocytes. ... 74 per cent. Large mononuclears 8 per cent. Lymphocytes 17 per cent. Transitionals 1 per cent. Spinal Fluid: November 11, 1919. Pressure Normal (fluid dropping out of needle) Appearance Perfectly clear Cells 18 lymphocytes Globulin Negative Wassermann 2 c.c. 1 o.c. .G c.c. .2 c.c. Alcohol antigen Neg. Nog. Neg. Neg. Cholesterin antigen . Neg. Neg. Neg. Neg. Urine Examination: November 11, 1919. Specific gravity 1.022 Reaction Acid Color Light amber Precipitate Slight flocculent Albumin None Sugar None Microscopical examination. . . . No casts, crystals or cells 136 EPIDEMIC ENCEPHALITIS Blood Wassermann: November 13, 1919. Alcohol antigen Negative Cholesterin antigen Negative November 23, 1919. Patient's general condition has improved much since admission. He complains no longer of insomnia, stating that he sleeps normally at night. During the day he does not feel stupid nor lie in bed apparently asleep as he did during the first week of his stay in the hospital. He now sits up in a chair all day long. His vision is much improved. He is able to read small newspaper print at a distance of 22 inches. The pupils are practicallj'- equal in size, each measuring about 3 milhmeters. Reaction to light and on convergence is normal. During the patient's stay in the hospital his tempera- ture was generally normal except for an admission temperature of 100°. SUMMARY The main findings on neurological examination were: The mental stupor, the paralysis of accommodation with preservation of the pupillary reflexes, inequality of the pupils, slight changes in the optic discs, absent ab- dominal reflexes on the right, and very slight general spasticity. The course was short, there being practically complete recovery seven weeks after the onset. CHAPTER XX CASE REPORT IV Miss M. S., Aged sixteen. Garment worker. Admitted to the hospital September 24, 1919. Chief Complaints: Drowsiness for seven months; muscular weakness for three months. Family History: Mother died in childbirth. Father well. Three brothers and three sisters living and well. Father has had chronic rheumatism. No illness in the family similar to the present one of the patient's. No cancer, tuberculosis, insanity or other nervous disorders. Personal History: She is a bright, lively girl; a shirt- waist maker. Drinks one or two cups of coffee a day and an occasional glass of wine. Has regular habits of eating and sleeping. Previous History: As far as she can remember she has never been ill before. No accidents or operations. No nervous trouble of any kind. Head: No headaches. Eyes: Moderately myopic, corrected by glasses. Ears: Normal; no discharge. Nose: She is not subject to colds. Mouth: Does not remember having sore throat. Has had some trouble with one bad tooth. Respiratory System: No cough or expectoration. Circulatory System: No palpitation, precordial pain or distress, no dyspnoea on exertion or swelling of the feet. Gastrointestinal: Appetite good; bowels regular. 137 138 EPIDEMIC ENCEPHALITIS Genito-Urinary : Urine is passed three to four times each day; no nocturia. Menstruation: Regular until the onset of the present illness. Periods began at fourteen and come at 30-day intervals, each one lasting five days. No dysmenorrhea or menorrhagia. N euro-Muscular: She has never been nervous ; always bright and happy. Progressed well in school work. Present Illness. Seven months ago as she was working in the factory she suddenly felt sick at her stomach and had a severe headache. There was no vomiting, chills, fever, cough or generahzed pain. She stopped her work and went home and was seen by a physician who told her she had influenza. This illness lasted about two weeks and was immediately followed by drowsiness. She slept most of the time and lost her usual vigor. She was easily aroused and would eat normally, but after eating fell into a deep sleep again. She was sent to the country for a few weeks hoping she would benefit by a change of air, but the condition continued the same. Three months ago her gait began to be slow and shuff- ling. She dragged her feet and complained of easy fatigue. To raise the feet from the ground took considerable effort. At present she is a little less drowsy but she wishes to remain quietly in bed or in a chair and sleeps a good deal of the time. Since the onset, her menstruation has been irregular. She has had only two periods in the past seven months, but there has been no headache, vomiting, fever or dizziness since the illness commenced. Physical Examination. General Appearance. A medium sized, rather stocky girl lying dorsally in bed. Her skin is dark, features rather coarse. The face is ex- pressionless except that she smiles whenever her attention is obtained, though she does not attempt to speak unless STUDIES OF SELECTED CASES 139 questioned. Her voice is weak, high-pitched and slight!}- tremulous. Head: The occipital region is rather flat. The head is held straight and motionless. There is no tenderness of the skull to percussion or pressure. There are beads of perspiration on the forehead. Eyes: The right palpebral fissure is narrower than the left. The pupils are round and centrally placed. There is no congestion oi- inflammation of the cornea or conjunctivae. Ears: There is no discharge or mastoid tenderness. Nose: The septum is deviated to the left; otherwise the nose is normal. Mouth: The teeth are in good condition. There is a slight tremor of the tongue. The tonsils are large but not acutely inflamed. Face: There is some facial asymmetry with flattening of the left side, and flattening of the left naso-labial furrow. Neck: There is a rather marked rigidity of the neck. The chin can be touched to the sternum but there is a spastic resistance to movement. There is no pain. Cer- vical lymph nodes are not enlarged. Thjn'oid not palpa- ble. No pulsations or masses. TJiorax: Well developed. Expansion good. Breasts are normal. Lungs are clear and resonant throughout, lireath sounds normal. Heart: Normal in size, action regular. No murmurs. Sounds of good quality. Blood pressure 108-55. Pulse 72. Abdomen is flat, relaxed. No tenderness, masses or signs of fluid. Liver and spleen not palpable. Extremities: No deformity or edema. Superficial Lymph Nodes are nowhere enlarged. Tem,perature 98.8°. Weight 1033^^ pounds. 140 EPIDEMIC ENCEPHALITIS NEUROLOGICAL EXAMINATION: OCTOBER 1, 1919. Voluntary Motor System. Abnormal Attitudes and Deformities. Patient lies dorsally in bed, remaining in the same attitude for long periods unless disturbed. Her eyes are partially closed. Her face is mask-like and expressionless. If she is aroused she opens her eyes and seems quite alert, though she does not speak spontane- ously, and answers questions promptly but with a slow, monotonous voice. Gait. Is slow and shuffling, her feet being scarcely lifted from the floor, her movements stiff. She is able to walk without assistance. Coordination. There is no Romberg or other sign of equilibratory incoordination. The finger-to-nose, heel-to- knee, pointing and past pointing tests are performed slowly but without deviation. There is no dysmetria. Rapid pronation and supination of the forearms is im- possible, but this is due more to the general spasticity and inability to move quickly than to incoordination. Skilled Acts. There is no dyspraxia or aphasia. Speech is slow, monotonous, weak and high-pitched. Reflexes: Deep Right Left Jaw 2 2 Biceps 3 3 Triceps 2 2 Radial 3 3 Ulnar 3 3 Patellar 3 3 Achilles 2 2 Superficial Ciliospinal Present Present Upi^er lateral abdominal Present Present Lower lateral abdominal Present Present Plantar flexion Present Present Babinski '. . . Absent Absent STUDIES OF SELECTED CASES 141 Abnormal Involuntary Movements. There is a rather fine tremor in the extended hands and arms, but no other involuntary movements. Muscle Strength. The patient is able to rise from the recumbent to the sitting or standingposition. The move- ments of the neck, shoulder, arm, forearm, hand, fingers, trunk, pelvis, thigh, leg and foot are all equal on the two sides, but are everywhere weaker than normal. Muscle Status. The muscles are well developed and of normal contour. They are hypertonic, there being a marked spasticity. There is much resistance to passive movement which is not constant, however, but shows well the phenomenon of cog-wheel release. Electrical Reactions are normal to both faradic and galvanic currents. There is no abnormal fatiguability. Abnormal Associated Movements. Not tested. Nerve Status. No observation. General Sensory. Touch, pain, temperature, vibra- tory, pressure, muscle tendon sense and stereognostic perception are normal. Cranial Nerves and Head. Olfactory Nerve and Nose: The sense of smell is normal. Optic and Oculomotor Apparatus. Visual acuity, roughly tested, is normal. There is no contraction of the visual fields. Ej^egrounds : There is slight blurring of the upper and lower margins of the optic discs on the right side. The physiological cup is absent. The vessels are slightly tortuous. There are no hemorrhages. The pupils are equal, circular and centrally placed. Thej^ react actively to light and on accommodation. The right pal- pebral fissure is narrower than the left. There is no evident exophthalmos, enophthalmos or strabismus. Conjugated eye movements are normal. In extreme lateral positions there is a slight transient nystagmus. 142 EPIDEMIC ENCEPHALITIS Acoustic Nerve and Ear. Hearing is normal. Air con- duction is greater than bone conduction on each side. Trigeminus Nerve and Mouth. The jaws can be moved normally in all directions. Corneal reflexes are present. There is no facial anaesthesia. Facial Nerve and Face. There is a flattening of the left side of the face with partial obliteration of the naso- labial fold and depression of the left corner of the mouth. There is no evident involvement of the upper face. Glossopharyngeus and Vagus Nerves, Pharynx and Larynx. The uvula is in the median position. The palatal and pharyngeal reflexes are present. Swallowing, respiratory and cardiac action are normal. Spinal Accessory Nerve. The sternomastoid and tra- ' pezius muscles are normal. Hypoglossus Nerve and Tongue. There is a constant slight tremor. The tongue is protruded in the midline and movements in all directions are normal. SUMMARY OF NEUROLOGICAL EXAMINATION 1. Mental inertia and somnolence. 2. General rigidity of musculatiu'e with marked cog- wheel resistance to passive movements. 3. Retardation of active movements with some ten- dency to catatonia. 4. Mask-like expression of face with weakness on the left side. LABORATORY EXAMINATIONS Blood Count: September 24, 1919. Red blood cells 5,600,000 Hemoglobin 85 per cent. White blood cells 7,700 Polymorphonuclear leucocytes 48 per cent. Lymphocytes 48 per cent. Eosinophils 4 per cent. STUDIES OF SELECTED CASP:S 143 Blood Wassermann: September 25, 1919. Alcohol antigen Negative Cholesterin antigen Negative Blood Urea: September 25, 1919. 0.3 gram per liter. Lumbar Puncture: September 25, 1919. 15 c.c. of clear colorless fluid removed under definitely increased pressure, a steady stream spurting about one inch from, the needle with noticeal^le pulsations. Globulin Negative Cells 4 lymphocytes Wassermann 2 c.c. 1 c.c. .6 c.c. .2 c.c. Alcohol antigen Neg. Neg. Neg. Neg. Cholesterin antigen. Neg. Neg. Neg. Neg. Colloidal gold 0010000000 Culture Sterile Urine Examination: September 25, 1919. Specific gravity 1.021 Reaction Acid Albumin None Sugar None Microscopical examination .... Few squamous epithelial cells No casts or crystals Lumbar Puncture: October 2, 1919. 15 c.c. of spinal fluid removed; first blood-tinged, then clear and colorless, under no increased pressure. Culture Sterile Glucose Tolerance Test: October 6, 1919. 78 grams of gluco.se (1.75 grams of glucose per kilo of body weight). Blood Sugar Urine Fasting 88 grams per liter No sugar 3 hours after glucose. . . .94 grams per liter 2 hrs. after glucose, no sugar 4 hrs. after glucose, very slight reduc- tion 6 hrs. after glucose, no sugar 144 EPIDEMIC ENCEPHALITIS Lumbar Puncture : October 7, 1919. Amount 10 c.c. Pressure Not increased Appearance Clear, colorless Globulin Negative Cells 2 lymphocytes Culture Sterile Clinical Notes: October 10, 1919: Patient is dis- charged to-daj'' in practically the same condition as on admission to the hospital. November 17, 1919. Miss S. is readmitted to the hospital to-day and states that she remained practicallj'^ the same for two weeks after discharge; but at the end of this time there appeared a tremor in the right hand. It was very slight at first but in a week or ten days be- came quite pronounced. At times there would also be a trembling of the right leg. The tremor varies in intensity but is present most of the time while she is awake, ceasing only on voluntary movement or when the trembling hand is held by the steady one. The tremor is aggravated by any excitement. She has also noted difficulty in standing. There is not much difference in walking, but on attempting to stand she feels as though she would fall backward and it is necessary for her to hold on to something for support. For the past two weeks she has had a constant excessive secretion of saliva which has been quite annoying. It runs out of her mouth at night if she is lying on her side. There has been no increased nasal secretion or excessive perspiration. She has had no pain, but her arm gets very fatigued from the constant tremor. Spinal Puncture: November 19, 1919. Appearance Perfectly clear Pressure Normal, the fluid flowing from the needle drop by drop Cells 4 lymphocytes Globulin Negative STUDIES OF SELECTED CASES 145 Fig. 27. Fig. 28. Fig. 27.— Case IV. Stiff, Slightly Flexed, Statuesque Attitude, with Tendency to Fall Backwards. Fig. 28. — Case IV. Parkinsonian Facies, Attitude and Tremor of Right Hand. 146 EPIDEMIC ENCEPHALITIS NEUROLOGICAL FINDINGS: NOVEMBER 22, 1919. The patient now presents a typical picture of a Parkin- son's disease showine; the four cardinal symptoms: 1. Muscular rigidity. 2. Impairment and retardation of active movement. 3. Characteristic tremor. 4. Difficulty in maintaining balance and character- istic modifications of gait. Besides these there are also added other symptoms, namely, uncontrolled smiling, left facial weakness and mental alteration. The muscular rigidity is quite marked, especially in the back, extremities and face. The head and shoulders are not inclined forward, but the back is held in a rigid, poker-like fashion. The arms are slightly abducted at the shoulders, and flexed at the elbows. The wrists are over-extended and the fingers slightly flexed at the metacarpo-phalangeal joint. On standing there is very little, if any, flexion at the hip or knee-joint. The features are fixed and expressionless, except for an uncontrolled, stereotyped smile provoked when anyone attracts her attention. Voluntary move- ments are performed slowly and stiffly and there is a marked resistance to passive movements with irregular, jerky release. The tremor is most pronounced in the right hand but is present in the right leg and to a less extent in the left hand. It is of fairly large amplitude and relatively slow. It involves the whole forearm and arm, and is a true shaking with little or no pill-rolling movement of the thumb and fingers. When excited, there is a similar shaking of the right leg. The tremor is stopped by active movement. The walking is slow, shuffling and unsteady, with a constant tendency to fall backward with a suppression of all automatic associated movements. STUDIES OF SELECTED CASES 147 The added features, smiling, facial weakness and mental alteration, do not belong to the Parkinson's picture, but are due to other lesions. The uncontrolled Fig. 29. — C.\se IV. Uncontrollable Smiling and Weakness of Left Side of Face. smiling is due to injury- of the fronto-thalamic fibers. The mental slowness and lack of spontaneity are char- acteri.stic of epidemic encephalitis. The facial weakness on the left side at her last admission was said to have 148 EPIDEMIC ENCErHALITIS been noted before the present illness commenced; but it seems to have increased during the past month. SUMMARY The onset was that of an acute infection which was said to be influenza. Two weeks later drowsiness appeared, and then a loss of strength and vigor. Four months after the onset the gait became slow and shuffling. Active movements were retarded and there was general muscu- lar rigidity. Eight months after the illness commenced, tremor and difficulty in maintaining balance developed. The Parkinson sj^ndrome was complete. CHAPTER XXI CASE REPORT V Mr. M. F., Aged fifty-three. Married. Tailor by occupation. Admitted to the hospital October 8, 1919. Chief Coni-plaints. Weakness, drowsiness, pains in both eyes, duration three weeks. Family History. Father died at 75, mother at 70. For some years before her death the mother had a tremor of the hands which prevented her from picking up things easily. One brother is living and well. One sister is living and well in Russia. No insanity, nervousness or chronic diseases in the family. Personal History. Patient has been married thirty 3'ears; his wife and three sons and two daughters are living and well. His habits are good. He uses alcoholic stimulants in moderation occasionally. Appetite, until the onset of the present illness has been good. Bowels regular. Past History. He was well all his life until two years ago when he had a short attack of nervousness. He and his famil}^ moved to the Bronx. He did not like the place and was unable to sleep. He used to get out of bed a dozen times a night and pace the floor. His physician advised him to move, and after doing so all his nervousness disappeared. He has been well ever since. Present Ilh^ess. On about September 15th he began to have shooting pains in the eyes. He continued to work for two daj's but on the third day they were so severe 149 150 EPIDEMIC ENCEPHALITIS that he had to remain at home. He then became weak and drowsy. His physician prescribed some eye drops, but he soon became more drowsy and unable to open his eyes, so the drops were discontinued. As the drowsiness became more marked the pain in his eyes disappeared, though he still was unable to open his eyelids fully. On October 3rd, while walking across the floor he suddenl}^ fell and was unable to get up or to speak dis- tinctly. By pounding on the floor he aroused the family, who got him into bed. When they arrived he could only speak in a whisper and indistinctly. The difficulty in speech has continued until to-daj- when it became much worse. This morning, before admission to the hospital, at about 4 A.M. he awoke and found he was unable to move his jaw. He could not talk or swallow. About five hours later he was able to talk a little though ver}^ indistinctly, but was still unable to move his jaw, his mouth remaining partially open. He has a slight frontal headache; has had no vertigo or convulsions, or clouding of consciousness. PHYSICAL EXAMINATION General Appearance. A rather thin, elderly man, lying partially propped up in bed, apparently in deep stupor. His head is retracted, his knees flexed. He may be aroused by repeated questioning. His skin is dry, cool and clear. Superficial lymph nodes are not palpably enlarged. Head is symmetrical. There are no tender areas. Eyes are partially covered by drooping eyelids and are staring directl}^ forward. There is no sign^of corneal or conjunctival inflammation. Ears and Nose are negative to external examination. STUDIES OF SELECTED CASES 151 Mouth is held partially open, the lower jaw being rigid, so that it is impossible to get a clear vision of the throat, but there appear to be patches of dry mucus on the posterior wall of the pharynx. The tongue is dry and coated. The teeth are in poor condition. The gums show moderate pyorrhea. Neck is stiff and resists bending forward or laterallj^ There is no thyroid enlargement. 152 EPIDEMIC ENCEPHALITIS Chest is rather poorly developed; expansion poor but symmetrical and equal. Lungs: There is no dullness. The voice and breath sounds are normal but there are many loud gurgling noises both on inspiration and expiration transmitted from the throat. Heart is normal to percussion. The apex impulse is in the fourth space, 9)-2 centimeters to the left of the midline. The sounds are of good quality. There are no murmurs. Blood pressure 140-100. The pulse is regular, full, of moderate tension with a slight thickening of the vessel wall. Rate 96. Abdomen is held rather rigidly. There are no masses, tenderness, or signs of fluid. The spleen and liver are not felt. Extremities: There is no edema or deformitj-. Rectal examination is negative. NEUROLOGICAL EXAMINATION: OCTOBER 10, 1919 Voluntary Motor System. A hnormal A ttitudes and Deformities. Patient is lying propped up in bed with mouth open, mask-like, emotionless face, eyes partially closed, staring directly forward, giving an extremely expressionless facial appearance. Gait. He is unable to stand or walk. Coordination. Muscular movements are carried out in a very slow, stiff, deliberate manner. He is able to touch his nose with the pointer finger of either hand with- out uncertainty of position. Heel-to-knee tests are less well performed, and show weakness, stiffness and ataxia. Skilled Acts. Pronation and supination of the fore- arms are slowly, stiffly and imperfectly carried out. There is no aphasia or apraxia. Speech is drawling, STUDIES OF SELECTED CASES 153 monotonous, almost unintelligible due to defective articulation. Reflexes. The jaw, pectoral, biceps, triceps, radial, ulnar, patellar, and Achilles reflexes are all present and Fig. 31. — Case \'. moderately active. The right biceps, knee and ankle jerks are more active than those on the left side. The abdominal reflexes are active. There is no Babinski or 154 EPIDEMIC ENCEPHALITIS modifications, but a spurious ankle clonus is elicited on the right side. Abnormal Involuntary Movements. There are no abnormal involuntary movements except that of the tongue, which shows a constant marked tremor, mainly of the protrusion type. Muscle strength is very difficult to test because of lack of cooperation, but the grip seems weaker in the right hand. He is unable voluntarily to sit up in bed, and all muscular movement shows decided weakness. There is a decided rigidity of all the muscles, but especially those of the extremities. Passive movements of all the extremities are inhibited by extreme rigidity which, however, shows some tendency to cog-wheel release. There is decided flexibilitas cerea, the limbs remaining for some time in any position in which they are placed. General Sensory. Sensory examination is difficult, but there seems to be no gross anaesthesia to touch or pain. Sense of position of his feet seems to be impaired. There is diminution in corneal sensibility on either side. Cranial Nerves. Olfactory Nerve and Nose. Smell is probably normal. Optic and Oculomotor Apparatus. Visual acuity is difficult to test, but he can tell the number of fingers held three feet away from each eye. The pupils are quite regular, each about 3 millimeters in diameter. The reaction to light is present, but a little sluggish in each eye. It is impossible to tell definitely about reaction to accommodation, on account of the ptosis and inability to converge. There is double ptosis, the palpebral fis- sures measuring 5 millimeters on each side. He is unable to open or voluntarily to close the eyes, although the blink- ing reflex is still present. There is no evident alteration in the anteroposterior position of the eyeballs. STUDIES OF SELECTED CASES 15.5 Both eyes appear directed straight forward. He is unable to move either eye upward or downward, and refuses to look to either side on command, but will follow with his eyes an object moved laterally when directed to do so, so that there is conjugate lateral excursion of the eyes which, however, does not extend to the normal degree. Fundi : There is slight haziness of the margins of the optic disc of the left eye. The vessels appear normal. There are no retinal hemorrhages. The right fundus is normal. Acoustic Nerve and Ear. Hearing is normal. Trigeminus Nerve and Mouth. 'The moutli is held rigidly in the half-open position, and he seems unable voluntarily to open or close it. He cannot move the jaw laterally or protrude it. It does move somewhat, how- ever, when he attempts to speak. The jaw jerk is active on each side. There seems to be no definite sensory dis- turbance in the fifth nerve area except for the hypaes- thesia of the cornea. Facial Nerve and Face. There is a decided mask-like expression of the face and an inability to retract the corners of the mouth. The left corner of the mouth is slightly lower than the right. Movement of the lips is present on attempting to speak, though it is imperfect. Glossopharyngeus and Vagus Nerves, Pharynx and Larynx. Swallowing is difficult and almost impossible. A satisfactory view of the pharynx cannot be obtained because of the rigidity of the jaw, but it appears to be normal. The pharyngeal reflex is hyperactive. Hypoglossus Nerve and Tongue. The tongue cannot be protruded beyond the lips, but shows a definite protrusion to the right and an inability to move it as far to the left as to the right. There is a constant coarse tremor which is not fibrillary. 156 EPIDEMIC ENCEPHALITIS LABORATORY EXAMINATIONS AND CLINICAL NOTES Spinal Puncture: Octobers, 1919. Pressure Considerably increased. First 5 c.c. spurted out of the needle. Amount 25 c.c. Appearance Perfectly clear Cells 9 lymphocytes Globulin Faintly po.sitive Culture Sterile Wassermann 2 c.c. 1 c.c. .6 c.c. .2 c.c. Alcohol antigen Neg. Neg. Neg. Neg. Cholesterin antigen. .. Neg. Neg. Neg. Neg. Blood Examination: October 8, 1919. Blood urea 13 grams per liter Blood Wassermann: Octobers, 1919. Alcohol antigen Negative Cholesterin antigen Negative Blood Culture: October S, 1919. Steiile Blood Count: October S, 1919. Red blood cells 5,600.000 Hemoglobin 85 per cent. White blood cells 1 1,000 Polymorphonuclear leucocytes. . 85 per cent. Urine Examination: October S, 1919. Specific gravity 1.022 Reaction Acid Color Amber Albumin None Glucose None Microscopical examination No casts, crys- tals or cells Spinal Puncture: October 11, 1919. 20 c.c. of slightly blood-tinged fluid removed under no in- creased pressure. Search was made for tubercle bacilli but none were found. STUDIES OF SELECTED CASES 157 October 11, 1919. Ankle clonus has disappeared. Spasticity is a little less marked; speech a little clearer. Slight divergent strabismus, but lateral ocular move- ments are still present. Mental functions are much clearer than his general condition would lead one to expect He endeavors to answer questions quickh'. VdiifA '" 0«, ol ticnik e 9 ao 11 12 13 1 Do) of liiHItl 21 22 23 25 26 , 37 1 Her 0/ D; i 8/i!*'»o 1 h» i ,m « t ,1 * t\iX • r It. r;»H r* • lf|a 1 rl,.J,^^y "i"!' 'I^i Pl^. To-.- ■■((■! ■ . ;!; ■'■ "^ ■ ■ \ 1 lidl 170 160 190 140 130 ItO 110 100 90 90 70 CO SO 40 108- - ■ 1 - ; . ! : ,»• ' ;i : : 'I' . .1 ,..| ; I: ■; : ; - • • ; ■ " ■1 • : ■ : ;i; .: -1- '- - ; ■ !, :|- ; ■1 '. \'\-.A ■ ■■■■ - ; ; : -108' ;;; ■|: : : '-\ : '■_ \ ; : : : . ■ '■A .'■' ,.-■% ' M ' i:! : ■\ ■ : /: i ..,.1 100- -m : • \ i- ">?(i J^t^ > "S ;_. — . — 100- w -sfiA ; 'Y ^ :i:| : : ::|: ii:i: :'■ : ; ■1; . \ / 11: m- ;j- : -■\ »T-- :i: :[;: : ; : i 'i ■ •i -j '■ :| - : .i- :i : :l;j: • I- ■ T ■1 : '; : ■.■.\: : 1 : \\' ; ■ :|:i: ': '■^\ : 'I:!: : ■' :!: _Ri tfvoh. «• tfi^i w mtti>» j«5W«itr,_ ^ Ji^^"| xs at i. i^ , _ 5^-iaJ IL L l1 Fig. 32. — Case V. Temperature and Pulse Chart During Final Week of Illness. Temperature Pulse October 12, 1919. As the patient is unable to swallow, it is necessary to feed him by lavage. Since admission there has been a general decrease in muscular strength, a disappearance of the catatonia and a diminution of the general spasticity. He is able to move his jaw and there is a very slight improvement in his speech. His 158 EPIDEMIC ENCEPHALITIS understanding is apparently normal. There is conjugate deviation to the left. October 13, 1919. Laryngeal Examination. There seems to be no paralysis. The cords do not move with respiration, and as there is no attempt made to pho- nate the cords are semi-abducted and show fibrillary twitchings. October 13, 1919. This morning the condition became very much worse. The hps are markedly cyanotic; there is a coarse gurgling in the throat, respiratorial rate is increased and rather shallow. The pulse is slow (40) full and well sustained. Pulse and respirations are absolutely synchronous in rate, each being 40. The blood pressure has risen to 170-110. October 14, 1919. During the past 24 hours the pa- tient's general condition gradually became worse. Cya- nosis became more marked. The respiratory rate rose to about 52, his pulse continuing in the 60's until shortly before death when it rose to 108, death apparently resulting from respiratory paralysis. The temperature during his stay in the hospital was never over 100.6°. The pulse varied from 40 to 108. AUTOPSY, OCTOBER 14, 1919 (Drs. Meleny and Pappenheimer) 7 hours p.m. The body is that of a middle-aged white man consid- erably emaciated, measuring 170 centimeters in length. Moderate rigor mortis. Slight lividity of the dependent parts. The skin is pale, the hair distribution normal. There is an abundant amount of gray hair on the scalp. There is a small abrasion of the skin over the sacrum. No edema. The conjunctivae are pale; no petechiae. No excretion from the nose, ears or mouth. Teeth are in a STUDIES OF SELECTED CASES 159 fair state of preservation except for one upper biscupid which is badly carious. No bridgework. The tongue is heavily coated with a thick white fur. There are no en- larged lymph ghintls. The alxlonien is protuberant apparently from gas in the intestines. There is a small pedunculated tumor on the outer aspect of the right thigh, apparently a lipoma. Abdomen: The panniculus is 1 centimeter in thick- ness. The large intestine is alternately distended with gas and tightly contracted in areas about 15 centimeters long. There are old, firm, fi])ious adhesions between the under surface of the liver, stomacii and omentum and between the omentum and transverse colon; also between the ascending colon and the lateral abdominal wall. The appendix is atrophic, 6 centimeters long, not ad- herent. There is no free fluid in the abdominal cavitj' nor any evidence of peritonitis. There is irregular con- gestion of the large vessels in the mesentery. The stom- ach is greatly relaxed and partially filled with fluid. The liver extends 1 centimeter below the costal margin on each side of the midline, but just reaches the costal margin in the right midclavicular line. The spleen ex- tends to 2 centimeters above the costal margin. The bladder is contracted; the diaphragm on the right side is at the level of the fifth rib; on the left side at the fifth space. Thorax: The mediastinum is apparentlj^ normal. The pericardial cavity contains 5 c.c. of clear fluid. No pericar- ditis. The pleural cavities are dry. Both lungs are adher- ent to the chest wall at their apices by very firm fibrous adhesions. Heart: Weighs 290 grams. Not apparently enlarged. In normal position; all cavities and valves appear normal. The endocardium has a few fibrous streaks in tlu* right 160 EPIDEMIC ENCEPHALITIS ventricle; otherwise it is normal. The myocardium ap- pears normal. Just above the aortic valve at the insertion of the cusps there are thin, atheromatous plaques. These are also present in the coronary arteries and in the begin- ning of the aorta. The Aorta is normal, elastic, has a few atheromatous plaques along its course. Left Lung: Weighs 470 grams, very firm, fibrous adhesions present at the apex with contraction of the lung tissue between them. The lung surface is gray in color with large anthracotic pigment. Posteriorly there is some congestion. There is apparently considerable emphysema. The lung does not collapse but is entirelj' air-containing. On section there is moderate congestion seen posteriorly, but practically no edema. The bronchi are considerably congested and contain a very small amount of fluid. The bronchial lymph nodes are small, the vessels normal. Right Lung: Weighs 530 grams. The adhesions are similar to those on the left, but with more contraction at the apex and just beneath the surface an abscess cavity containing thick brownish yellow pus is opened, having- a thin fibrous wall. No connection with the bronchus is demonstrated. Scattered over the upper and lower lobes are raised areas about 2 centimeters in diameter of the same color as the rest of the lung, but slightly firmer. Posteriorly there is congestion. On sec- tion the small bronchi contain thick yellow pus. The large ones contain thin mucopurulent fluid. No other abscesses are encountered. The firm raised areas are seen to be masses of minute gray nodules 1 millimeter in diameter, apparently tubercles. The bronchial lymph nodes and vessels are unaltered. Thymus: No tissue demonsti-able. STUDIES OF SELECTED CASES 161 Liver: Weighs 1460 grams. Color is dark red on the surface and reddish brown on section. The lobules are reddish brown at their centers, brown at the periphery. There is apparently a moderate degree of chronic passive congestion. There is a slight increase of fibrous tissue; the vessels appear noi-mal. Gall-bladder: It is surrounded b}' thick fibrous ad- hesions which partially constrict it. It is only partially filled with thick, olive colored bile. The wall and the mucosa appear normal. The ducts are patent. Spleen: Weighs 110 grams. The capsule is wrinkled. The color is blue; consistency flabby. On section it has a dark reddish brown color. It is moderatel.y firm. The corpuscles are indistinct. The trabeculae ai'e normally prominent. Adrenals are apparently unaltered. Kidneys together weigh 360 grams. They are equal in size, somewhat flabb3^ The capsule strips easilj'' leaving a surface of grayish red with stellate veins congested. On section it shows considerable congestion. The stria- tions are prominent. The glomeruli appear normal. The cortex averages 6 millimeters in thickness. The pelvis and ureters are slightly congested. Bladder is contracted. It contains 25 c.c. of cloudy yellow urine. There are a few submucous petechial hemorrhages. Prostate: Both lateral lobes are considerably enlarged and equal in size, each being 2.5 millimeters broad and 2 centimeters high. On section each lobe seems to contain adenomata. The middle lobe is not enlarged. Testicles are normal. Gastrointestinal Tract: The esophagus is normal. The stomach is greatly enlarged, containing greenish brown fluid. The mucosa is pale and considerably digested. On 162 EPIDEMIC ENCEPHALITIS the posterior surface, about the middle, is a submu- cous hemorrhage 1 centimeter in diameter, but no scar or ulcer beneath it. The duodenum shows many sub- mucous hemorrhages. The jejunum and ilium are normal. The large intestine is normal. The rectum shows general congestion. Organs of the Mouth and Neck: Nothing remarkable. Head: The brain is considerably congested. The meninges slightly congested. No gross abnormalities found on section.- The sinuses and middle ear are negative. Spinal cord is grossly normal except for congestion. Microscopical. Examination of Nerve Tissue. The pia mater over the surface of both brain and cord is congested. There are a few hemorrhages between the pial layers but no cellular infiltration. Sections of the cortex show a very slight degree of alteration but no distinct change in the pyramidal cells. There is distinct vascular congestion which is more pronounced in the deeper layers. In the internal capsule and deep white matter there are localized areas of cellular infiltration. The cells forming these accumulations are largely ameboid glia cells. In the optic thalamus there is extreme capillary congestion, and in some portions of the internal capsule bordering on the thalamus there are areas showing diffuse cellular accumulation. Many of the thalamic cells are swollen and misshapen. The nuclei appear normal but are eccentrically placed. A good deal of fat pigment is noted in the cytoplasm. Satellitosis is present in some areas and in a few instances there are severe destructive cell changes and active neuronophagy. The medium sized vessels in this area have an accumulation of lympho- cytes in the Virchow-Robin space. There are a few small hemorrhages which are not infiltrating and for the main part are confined to the pei'ivascular space of His. STUDIES OF SELECTED CASES 163 The invading cells are mainly ameboid glia, though lymphocytes, polyblasts, plasma cells and rarely poly- morphonuclear leucocytes are observed. In the medulla there are small hemorrhages, adventitial lymph space infiltration of some of the vessels, edema and scattered areas of cellular accumulation. The nerve cells in some instances show the early changes of acute cloudy swelling, but nowhere to a marked degree. Neuronophagy is absent. In the cord there is marked congestion of the gray matter and to a less extent of the white. Here the motor cells show evidence of moderate acute cloudy swelling. In conclusion, the findings are chiefly marked vascular congestion which is more prominent in the gray matter of both brain and cord than in the white matter, but most pronounced in the central ganglia. There are small hemorrhages, Virchow-Robin space infiltration and local- ized areas of edema and cellular accumulation, the cells outside of the vessel spaces being niainly ameboid glia cells, but occasionally lymphocytes, polyblasts, plasma cells, and very rarely polymorphonuclear leucocytes are seen. The changes in the motor cells are nowhere marked and consist mainly of the milder grades of acute cloudy sweUing. CHAPTER XXII CASE REPORT VI Mr. M. P Aged forty. Married. Cabinetmaker. Admitted to the hospital June 1, 1919. Chief Complaints. Involuntary movements of the head and legs, difficulty in walking, tremor of the hands, constipation; duration five months. Fmnily History. Parents are dead; cause unknown. Three sisters are living and well; two brothers dead, one killed in Russia, the other died of appendicitis. No famil- ial diseases. No nervous or mental affections. Previous History. Scarlet fever, diphtheria in child- hood. Appendix was removed three years ago. He has had occasional colds and sore throat ; no severe tonsillitis. No rheumatism or chorea. No nervous disorders. Vene- real diseases denied by name and symptom. Personal History. He has not worked at his occupa- tion of cabinet making since the onset of this illness, owing to his involuntary muscular movements. He has been married seventeen years; his wife is well, except for attacks of asthma. He has had six children; four are living and well; two died, one from scarlet fever and the other from meningitis. The first pregnancy resulted in an early miscarriage. There have been no other miscarriages. He uses no alcoholic drinks. Until the onset of the pres- ent illness he smoked eight or ten cigars daily. Takes two cups of tea daily, coffee only occasionally. Use of drugs is denied. 164 STUDIES OF SELECTED CASES 165 Present Illness: Toward the end of December, 1918, the patient began to have a continual ringing in the ears associated with general weakness. A week later he sud- FiG. 33. — Ca!sk VI. Series of t'hutugnqui^ ^liuwin^ lik- \ arious Phases of Movement continually Present. No. 1. denly felt ill and went to bed. A physician who was called made a diagnosis of influenza. During the first few daj^s of the acute illness he had a fever accompanied by a cough and delirium. This was followetl by progressive 166 EPIDEMIC ENCEPHALITIS drowsiness which merged into true lethargy. During this period the patient did not recognize his wife. He was fed with chfficulty, had extreme difficulty in keeping Fig. 34.— Case VI. No. 2. his eyes open, and when they were open his eyeballs would roll upwards. There was no strabismus or incoordi- nation noted. The wife noted a flattening of the left side of his face, a very peculiar appearance of his eyes and STUDIES OF SELECTED CASES 167 an entire change of expression. The lethargic state lasted three to four weeks. After this there was a period of dullness and the patient was perfectly cognizant of his Fig. 35.— Case VI. No. 3. surroundings. He complained of occipital pressure and dizziness, but no earache. For several days he had diffi- culty in swallowing and ever^'-thing he ate would be regurgitated. The patient has only a vague memory of 168 EPIDEMIC ENCEPHALITIS events during this time. He gradually emerged from the drowsy state, and got up. For the next two or three days he had visual hallucinations which frightened him and caused him to break out in cold perspiration. Fig. 30. — Case VI. No. 4. After recovery he was quite normal for two v/eeks, but rather weak and had a continual feeling of oppression in the occipital region. Then he began to have involuntary STUDIES OF SELECTED CASES 1G9 irregular movements of his head. These were mild at first but got progressively worse. After a while the movements would occur when he was lying down. His hands got shaky so that he could not hold a newspaper. Then he began to have involuntary movements of his right leg which were synchronous with the head movements. This, combined with a feeling of weakness in the knees, made walking very difficult. 170 EPIDEMIC ENCEPHALITIS Ever since the onset of his illness the patient has had severe constipation. For the past five months he has not had a stool without having previously taken a cathartic. Fig. 38. — Case VI. Composite Photograph with Five Exposures on One Plate Showing Movement of Head. Except for his nervous symptoms he has felt well since his acute illness. His appetite is fair. He has occasional indigestion (a burning sensation in the epigastrium after meals), no nausea or vomiting; no distension or flatulence; STUDIES OF SELECTED CASES 171 no fever, cough, dyspnea or headache. There has been no trouble with vision. The ringing in the ears still occurs fre- quently, but he has had tinnitus for many years. At times he has a discharge from one of his ears. He has had no genito-urinar}' symptoms; no incon- tinence at any time. Dur- ing his illness he has gained in weight. PHYSICAL EXAMINATION General Appearance. A well developed, well nourished, middle-aged Russian Hebrew. He does not appear ill. There is no cyanosis, edema or dys- pnea. As the patient lies with his head on the pillow he is quiet. On sitting up, however, there are curious involuntary movements of the head and neck which consist of a jerking back of the chin at frequent in- tervals with lateral flexions of the head to one side or the other. There is also rota- tion of the head to either side. These movements are -Case VI. Attitude. Standing 172 EPIDEMIC ENCEPHALITIS stereotyped, and follow one another in a regular se- quence. They are not attended with any pain. There are no abnormal movements of the eyes. There is some diffi- culty in speech apparently due to lack of coordination in the muscles of the lips. The skin is warm and dry with a slight acneform eruption over the back. Lymphatic System: There is no glandular enlarge- ment. Head: The scalp is clean. Eyes: Conjunctivae are not injected; movements are normal. No exophthalmos, strabismus, nystagmus or ptosis. The pupils are equal, regular aiid react normally. Nose and ears are negative to external examination. Mouth: The teeth show moderate caries and pyorrhea with many gold caps. The tongue is heavily coated. The pharynx is moderately congested about the fauces. The tonsils are slightly enlarged and congested. Neck shows no abnormalities; no stiffness. Chest is symmetrical; expansion is moderate and equal on the two sides. Lungs are resonant throughout. Breath sounds, voice and fremitus are normal. There are no rales. Heart is normal in size and position. The apex beat is not felt. There are no abnormal pulsations or thrills. The sounds are not well heard at the apex or base, but appear to be of good quality. The left limit of dullness is 103^ centimeters to the left of the midline in the fifth space. The pulses are equal and regular; the rate and tension are normal. Rate, 88. Blood pressure 145-90. Abdomen is soft. No abnormal tympany. No masses or tenderness. Liver and spleen are not felt. Genitals are normal. Extremities: There is a coarse tremor of the hands which is made worse by voluntary movements. There is STUDIES OF SELECTED CASES 173 no cyanosis or edema. There is occasional involuntary movement of the right leg which consists of sudden slight flexions of the knee. Temperature 99. Respirations 20. Weight 11 G pounds. LABORATORY EXAMINATIONS Blood Wasserynann: Juno 2, 1919. Alcohol antigen Nofj;ative Cholesterin antigen Nejiativo Blood Count: June 2, 1919. Red blood cells .''),000,000 Hemoglobin SO per cent. White blood cells 12,000 Polymorphonuclear leucocytes. . 67 per cent. Lymphocj^tes 30 i)er cent. Transitionals 2 per cent. Basophiles 1 per cent. Urine Examination: June 3, 1919. Specific gravity 1.021 Reaction Acid Precipitate Slight Albumin Negative Sugar Negative Microscopical examination Negative Lumbar Puncture: June 4, 1919. Amount 9 c.c. Appearance Colorless, clear Pressure Normal Cell count 61 lymphocytes Globulin + Wassermann 2 c.c. 1 c.c. .6 c.c. .2 c.c. Alcohol antigen Neg. Neg. Neg. Neg. Cholesterin antigen . . . Neg. Neg. Neg. Neg. Colloidal gold Negative Eye Examination: June 13, 1919. Retinal arteries are thin. Otherwise the eyegrounds are negative. There 174 EPIDEMIC ENCEPHALITIS is possibly a slight insufficiency of the right internal rectus. Vision is normal. NEUROLOGICAL examination: JULY 8, 1919 Voluntary Motor System. Abnormal Altitudes and Dejormities. As the patient lies in bed there is almost constant movement of the head. When it is quiet the face is turned to the right, head inclined to the right and backwards. The movement, though it varies in severity and amplitude, follows a pretty constant formula. Start- ing with the head at the back and right, it moves back- ward and to the left, then forward and to the right again. Throughout the movement there is a tendency to maintain the tilting of the head to the right and back- wards. The movement is never in the reverse direction. It is more active when he lies on the right side. It is also increased by any excitement, for instance, during examination, when he is talking, playing checkers, or if he reads anything especially interesting or exciting. On standing, both legs are flexed at the knees, the left more than the right, the alidomen is thrown forward with some arching of the back, the head is in the position described before. When quiet in bed there is no particular position in which the arms are held; but when he attempts to walk, the right forearm is pronated partially flexed, and the hand held midway between the open and closed position. The arm is internally rotated so that the palm is held outward and backward. Gait. On walking there is the constant movement of his head already described. His body is inclined forward, both legs are kept slightly flexed at the knees. The steps are of about normal length and equal on the two sides; the feet are raised from the floor a little more than is normal and the toes brought down to the floor before the heels. STUDIES OF SELECTED CASES 175 Coordination. Equilibratory: Standing with feet to- gether, eyes open, there is ver}^ sHght swaying. The sway- ing is more marked when his eyes arc closetl, but he does not feel dizzy. Non-equihbrator}^: Finger-to-nose: The movements are made with only moderate ataxia, but with a slight over-reaching on each side. Pointing and past point- ing: There is an over-reaching of about two inches in movements in the lateral planes with each liand. The movements in the vertical plane are well coordinated. Heel-to-knee: The heels are placed three to six inches above the knees on each side. As a rule there is more over-reaching with the left leg. The movements are carried out quickly and with very little oscillation. Toe-to-object-above-recumbent-patient test is accom- plished quite well on each side. Dysmetria: There is none with the eyes open. Adiadochokinesis is absent. Skilled Acts. There is no dyspraxia. Speech is usually slow and apparently accomplished with some effort. Most of the difficulty with his speech seems to l)e due to the constant movement of his head rather than to any inherent disorder of the speech mechanism. There is no aphasia. Reflexes: Deep Right Left Jaw 2 2 Pectoral 2 2 Biceps 2 2 Triceps 2 2 Radial ' 2 2 Ulnar 2 2 Wrist 2 2 Suprapatellar 2 2 Patellar 3 2 Achilles 3 2 Periosteal uncrossed Absent Alisent Periosteal crossed Absent Absent 176 EPIDEMIC ENCEPHALITIS Superficial Right Left Ciliospinal Present Present Supra-umbilical 2 2 Suprapubic 2 2 ITpper lateral abdominal 2 2 Lower lateral abdominal 2 2 Cremasteric 2 2 Plantar flexion Present Present Bahinski and modifications Absent Absent On testing for plantar reflexes there is a slight plantar flexion of the toes, but a very marked contraction of the tensor fascia femoris. Ah normal Involuntary Movements. There is a slight fine tremor of the extended fingers. The movement of the head is described under "Abnormal Attitudes and Deformities." Muscle Strength. The patient is left-handed. He writes with his left hand, uses the saw and most of his cabinet-making tools with the left hand, but uses the plane with his right hand. There is considerable diminu- tion of strength in the muscles of all extremities, the grip on the left side being a little better than on the right. Otherwise there is no perceptible difference in the strength of the homologous muscle groups on the two sides. There is some weakness of the lower portion of the face on the right side. Muscle Status. The contour is normal, consistency soft, the tone is normal. General Sensory: Touch: Acuity, localization, dis- crimination are normal. Pain and temperature sense are normal; vibratory — tuning fork vibration is said to be felt a little less acutely in the left leg. Pressure over the muscles of the calf and thigh is felt slightl}^ less well on the left side. JXIuscle tendon sense is normal. Stereognosis is normal. STUDIES OF SELECTED CASES 177 Cranial Nerves and Head. Olfactory Nerve and Nose. The sense of smell is not very acute on either side. The odor of asafetida is detected but said not to be unpleasant. Optic and Oculomotor Apparatus. Visual acuity is normal. Perimetry, by the finger test is normal. Eye- grounds : The retinal vessels are not abnormally tortuous or congested. There are no hemorrhages. The disc is well outlined. The pupils are both in mid-dilatation and react actively to light and on accommodation. The palpebral fissure measures 10 millimeters on each side. There is no enophthalmos, exophthalmos or ptosis. There is no strabismus or other ocular deviation. The conjugated eye movements are normal. There is no nystagmus. Acoustic Nerve and Ear. A watch is heard eighteen inches from each ear. Air conduction is better than bone on each side. Trigeminus Nerve and Mouth. Taste on the anterior two-thirds of the tongue on each side is normal. There is slight weakness in the lower face on the right side, but no apparent weakness of either orbicularis palpebrarum. Glossopharyngeus and Vagus Nerves, Pharynx and Larynx. The uvula hangs in the median position. The palatal and pharyngeal reflexes are present. Swallowing is normal. Spinal Accessory Nerve. There are no signs of paraly- sis on either side. Hypoglossus Nerve and Tongue. The tongue is pro- truded shghtly to the right of the median Hne, but the movements seem to be equal in all directions. There is a slight ataxia noted in the rapid movements of the tongue. It can be moved back and forth and laterally quite quickly, but cannot be moved rapidly in the up and down direction. 178 EPIDEMIC ENCEPHALITIS Mental Status, At present the patient is perfectly clear mentally. He complains of a lack of memory for recent events, but his memory for past events is good. He has some difficulty in thinking of words that he wishes to use but seems quick and alert and able to think promp- tly. Some months ago he had visual hallucinations, but these have entirely disappeared. He states that at times strange thoughts come into his mind without obvious association or reason. He realizes that this is abnormal and it worries him a little, but he believes that it will pass away and he does not wish to discuss it. He is con- fident that he will entirel}^ recover and is not in any way worried about his condition. The patient remained in the hospital six weeks, his condition gradually improving. His gait became steadier and the tremor of his hands practically disappeared. The movements of his head, although much diminished, still persisted and were exaggerated by emotional influ- ences. His speech difficulty which apparentl}^ depended largely upon the constant movements of the head, was much less. While in the hospital the treatment consisted of rest and anti-constipation diet and regime. July 25, 1919. A note from the patient states that there has been but little improvement since leaving the hospital, the movement of the head still being almost continuous. CHAPTER XXIII CASE REPORT VII Mr. N. H. Aged thirty-two. Married. Chemist. Admitted to the hospital June 12, 1919. Chief Com'plaint. Difficulty in walking and speech, duration five months. Family History. Mother is living and well; father is dead, cause unknown. Two brothers and three sisters are living and well. Personal History. He is a chemist. Has been married three years. His wife is living and well. He has one healthy child. His wife had one miscarriage last winter, at four months. He uses no alcohol, tobacco or drugs. Takes tea occasionally; no coffee. Past History. Has had no serious illnesses, never having been sick in bed before. Has had severe acne since the age of 15, with numerous boils and carbuncles. He had pains in the legs for six months prior to present ill- ness. Gonorrhea and sj'philis denied. Soft chancre six years ago. Present Illness. The onset of the present illness was five months ago following an attack of influenza. He was sick with a mild fever and general pains for three weeks in the Brooklyn Jewish Hospital. The following report was obtained from this hospital: The patient was ad- mitted on January 19, 1919, complaining of fever, cough and substernal pain, of six days' duration. The family, past and personal history were good except that he had had influenza three months prior to admission. 179 180 EPIDEMIC ENCEPHALITIS During his stay in the hospital he ran a temperature ranging from 104 to 105°. He had typical signs of pneu- monia of the right lower lobe. The pulse was very rapid. He was markedly dyspneic with signs of slight pulmo- nary edema. His abdomen was markedly distended and he suffered from bladder retention and had to be cathe- terized repeatedly. On the fifth day the patient had a crisis which was followed by an apparently normal con- valescence. For the next two days he appeared asthenic, but not more so than is seen in convalescence from severe pneumonia. On the third day of convalescence he could be roused only with difficulty and slept most of the time. When asking for something it was noticed that he could speak only in a whisper. Following this he became some- what restless. His thinking was very slow and he voided involuntarily. He was conscious of this fact and worried over it. The difficulty in speech became worse, so that he could talk only with exertion. He pronounced his words indistinctly. The neurological findings at this time were as follows: Speech slow and scanning; slight weak- ness of the left side of the face; both knee jerks very active; slight ankle clonus; no Babinski. Abdominal reflexes were normal. There was marked ataxia of the lower extremities. There was some difficulty in swallow- ing but the throat examination showed no paralysis of the palate or pharynx. The mentality was normal. The pupils reacted actively to light and on accommodation. The ocular movements were normal, there was no nystag- mus and both fundi were normal. As time went on his appetite improved. Urination and defecation became normal. He was mentally perfectly clear but he still had marked difficulty in speaking. His face remained expressionless. There was a moderate leucocytosis at the time of his STUDIES OF SELECTED CASES 181 pneumonia. His urine showed a trace of albumin. Blood pressure was normal; blood culture sterile. Sputum examination showed non-hemolitic streptococci and staphylococcus pyogenes aureus. The patient was discharged February 21, 1919, the pulmonary condition having entirely cleared up. He was still markedly weak, his face was expressionless, speech slow and difficult, and gait ataxic. The weakness and difficulty in walking that were noted on his leaving the Brooklyn Jewish Hospital have persisted up to the present when he is unable to walk without a cane. If he attempts to walk unaided he sways and usually falls. There is no tendency to fall in any particular direction. Since the onset he has had difficulty in talking; he knows what he wants to say, but has a hard time forming the words. At times he has severe frontal headaches; these come on usually at night and last only a few minutes. Occasionally he vomits small quantities. This often occm's while going to bed. It is not associated with headaches or accompanied by nausea. His appetite is poor. He sleeps poorly. The bowels are regular. The general health is fairly good; he has gained some weight recently. He has not been able to work, owing to the difficulty in walking and in speech. PHYSICAL EXAMINATION, JUNE 12, 1919. General Appearance. A healthy-looking, well-nour- ished Hebrew of 32. Good color. No dyspnea or cyanosis. He lies in bed apparently comfortable, seeming some- what apathetic. His face has a singular lack of expression. His speech has a deliberate, emphatic quality, is some- what jerky and has a scanning chairacter; it is low-pitched and monotonous. He has a curious bodily configuration, 182 EPIDEMIC ENCEPHALITIS the legs appearing too short for the trunk. The shortening is in the bones of the legs which are very slender compared with the rounded fat thighs. Fullness of the thighs and the knock-knees give a feminine character to the appear- ance. The genitals are under-developed; crines pubis flattened above, absence of pectoral hair. The hands and feet are small and delicate. There is slight nodding of the head. The skin is warm and oily. Over most of the body, but most noticeable over the back, chest and thighs, there is an extensive indurated acneform eruption consisting of comedones, papules and large pustules. There are numerous scars of all sizes resulting from inci- sions of previous furuncles. Lymphatic System: No glandular enlargement. Head: Scalp: The hair is thick and oily with a low hair-line. Face: Skin oily; several scars and fresh papules. There is an absence of facial expression and no spon- taneous smiling. There is very little movement of the left angle of the mouth in talking. Nose: Wide anteiior nares. No obstruction or discharge. Ears: Negative. Eyes: Conjunctivae and sclerae clear. Movements nor- mal. Pupils small and regular, the right slightly larger than the left. Both react promptly to light and on accommodation. Mouth: Lips are of good color. Teeth show moderate pyorrhea; several gold crowns. Tongue is clean. Pharynx is somewhat reddened. Tonsils not enlarged. Neck: No thyroid enlargement or other abnormality. Chest: Symmetrical but poorly developed. Expansion is limited on both sides. The lungs are resonant through- out. Breath sounds are diminished owing to inability STUDIES OF SELECTED CASES 183 to breathe properly. Fremitus and voice sounds are normal. There are no rales. Heart is normal in size and position. Apex impulse is not felt. No abnormal pulsations or thrills. The rate is rapid but regular; tension normal. The sounds at the apex are of good quality, at the base the aortic second sound is slightly greater than the pulmonary second. There are no murmurs. Pulses are equal, regular, rate 92. Blood pressure 148-90. Abdomen is full and rounded, soft, moderately tympani- tic; no masses or tenderness. Liver and spleen not felt. Genitalia are small. Extremities: No cyanosis or edema. All the deep reflexes are hyperactive. There is a coarse tremor of the hands. LABORATORY EXAMINATIONS Lumbar Puncture, June 13, 1919. 18-20 c.c. of spinal fluid obtained under normal pressure were clear and colorless. The fluid then became bloody. Toward the end of the aspiration the amount of blood became progressively less. Cells (Fluid bloody) Globulin not determined (Fluid bloody) Wassermann 2 c.c. 1 c.c. .2 c.c. .6 c.c. Alcohol antigen Neg. Neg. Neg. Neg. Cholesterin antigen . . . Neg. Neg. Neg. Neg. Culture Sterile Blood Count: June 13, 1919. Red blood cells .'i,000,000 Hemoglobin 85 per cent. White blood cells 29,700 Polymorphonuclear leucocytes. . 59 per cent. Lymphocytes 40 per cent. Eosinophiles 1 per cent. 184 EPIDEMIC ENCEPHALITIS Urine Examination: June 14, 1919. Specific gravity 1.020 Reaction Acid Color Amber Precipitate Slight Albumin A very faint trace Glucose None Microscopical examination A few amorphous urates Blood Count: June 20, 1919. White blood cells 20,000 Polymorphonuclear leucocytes 63 per cent. Lymphocytes 37 per cent. Eye Examination: June 13, 1919. (Dr. Schoenberg). The left cornea is less sensitive than the right. There is no ptosis or convergent insufficiency. Both fundi are normal. Vision is normal. NEUROLOGICAL EXAMINATION I JUNE 27, 1919 Voluntary Motor System. Abnormal Attitudes and Deformities. Previously described. Gait. He is unable to walk unaided. When hands are supported he walks with feet far apart. The knees are brought up high, the feet planted down flatly. Coordination. Equilihratory: Standing with the feet together, eyes open, there is marked swaying, with eyes closed the swaying is somewhat increased. He is unable to stand on either foot unaided. Non-equilibratory: Finger-to-nose test: The movement on each side is attended by slight ataxia. Heel-to-knee test is accom- plished with a good deal of wobbhng of the foot, the heel at last being placed above the knee on each side. Dys- metria is not present. Adiadochokinesis : The movements of pronation and supination are rather slow and delib- erate, but not irregular. STUDIES OF SELECTED CASES 185 Skilled Acts. There is no dyspraxia. Speech is slow, difficult, scanning, low-pitched, with very little inflec- tion. The hand-writing is poor, due to the marked tremor of the hands. Reflexes: Deep Right Left Jaw 2 2 Pectoral 2 2 Biceps 3 3 Triceps 3 3 Radial 3 3 Ulnar.. .■ 3 3 Wrist 3 3 Scapular 3 3 Patellar 4 4 Achilles 4 4 Periosteal uncrossed Present Present Periosteal crossed Present Present Superficial Ciliospinal Present Present Abdominal All present, but are easily fatigued so that they disappear after being elicited a few times, the disappear- ance occurring at the same time on each side. Cremasteric 2 1 Plantar flexion Present Present Babinski Absent Absent Abnormal Involuntary Movements. There is a moderate tremor of both hands made slightly worse by voluntary eft'ort. Muscle Strength. The patient complains of general weakness. This is not particularly evident when muscle strength is tested. He says that his neck becomes tired when he holds his head up, his back tires when sitting 186 EPIDEMIC ENCEPHALITIS up, his limbs feel weak when he attempts to stand. There is no apparent difference in the weakness on the two sides. Muscle Status. The muscles everywhere seem well developed. Consistency and tone are normal. Abnormal Associated Movements. None present. Nerve Status. Nothing noted. General Sensory. Touch: Acuity, localization and discrimination normal. Pain normal. Temperature (cool and warm) normal. Vibratory normal. Pressure, muscle tendon sense and stereognosis normal. Cranial Nerves and Head. Olfactory Nerve and Nose. Smell is normal on each side. Optic and Oculomotor Apparatus. Visual acuity is normal. Perimetry, roughly tested, normal. Eyegrounds normal. Pupils in mid-dilatation, regular and equal. Reaction to light and on accommodation normal. Palpe- bral fissures are equal, each measuring 10 millimeters. There is no exophthalmos or enophthalmos; no ptosis. Strabismus is absent. Conjugated eye movements are normal; nystagmus is absent. Acoustic Nerve and Ear. A watch is heard at twenty inches from each ear. Air conduction is greater than bone on each side. Trigeminus Nerve and Mouth. The patient is unable to move his jaw forward or sideways; he says that he has never tried to do this. The conjunctival reflex is present on each side the left cornea being slightly less sensitive than the right. Facial Nerve and Face. The right side is normal. On the left side there is a slight weakness of the lower facial muscles evidenced in attempting to show his teeth. Taste on the anterior two-thirds of the tongue on both sides is normal. STUDIES OF SELECTED CASES 187 Glossopharyngeus and Vagus Nerves, Pharynx and Larynx. The uvula is in the midline. Palatal and phar- yngeal reflexes are normal. There is no difficulty in swallowing. Spinal Accessory Nerve is normal. Hypoglossus Nerve and Tongue. The tongue is pro- truded in the midline. He is unable to move the tongue quickly in any direction. He cannot fold the tongue or produce a rapid up and down or lateral oscillation of the tip. The trophic status of the tongue is normal. During the patient's nine weeks' stay in the hospital he gradually improved with rest and massage. His walking became steadier and less spastic and all of his movements better coordinated. His writing, which has been nearly bej'^ond recognition was markedly improved. The speech remained difficult and little changed. November 30th, 1919. A note from the patient states that his condition has remained almost stationary since leaving the hospital. CHAPTER XXIV CASE REPORT VIII Mr. S. K. Aged twenty-eight. Occupation, Locomotive fireman. Admitted to hospital December 1, 1919. Chief Complaint. Clumsiness and stiffness in right shoulder, arm and hand, and to a less degree in the right leg. Duration ten months. Family History. Mother died of pneumonia aged fifty- eight; father died of pneumonia at the age of sixty- seven. Two brothers and three sisters are well. No history of nervous disorders in the family. No heart or kidney trouble. Personal History. The patient is single. His work is strenuous, occupying eight hours a day. He smokes ten cigarettes and drinks four glasses of beer and one of whiskey daily. His best weight was 145 pounds one year ago. He now weighs 133. Previous History. No operations. Measles when twenty-one or twenty-two. Jaundice when seventeen which lasted one week. Head: No headache prior to an attack of influenza ten months ago. Eyes, ears and speech were negative prior to this illness. Nose: Negative. Teeth bad; had some dentistry. Respiratory: No grip, bronchitis or pneumonia. No night sweats. 188 STUDIES OF SELECTED CASES 189 Gastrointestinal: Had bloody diarrhea when a child. Duration three days. Cardiovascular: Negative. Genito-Urinary : Urination four to five times a day, once or twice at night. No dysuria or incontinence. Gonorrhea and lues denied. Since the attack of influenza he has been impotent. Neurological: Negative up to the time of this illness. He is not nervous. His memory is good. Present Illness. About ten months ago he had influ- enza and was in bed ten days with prostration, fever, aches all over body, cough and sputum which was never blood-tinged. Was not treated by a physician. He slept a great deal during his illness and was drowsy and dull. He did not work for the following three weeks and during the first week after getting up he complained of frontal headaches nearly every morning. These headaches were dull in character. At this time he had trouble with his vision. Near objects were blurred so that he was unable to read anything, while distant objects were seen as clearly as ever. There was no double vision. This condition con- tinued for two to three weeks and gradually cleared up. He was first able to read large print and a little later small type could be seen as plainly as before he became ill. His hearing also became poor. It was diminished to about the same extent in each ear. Soft sounds were not heard at all and louder noises seemed distant. His speech became slower and slurring. He runs words to- gether and at times has difficulty in spealdng. The head- aches, visual disorder and poor hearing lasted two or three weeks, the speech change has remained. His hear- ing is good now except that when he is over-fatigued it is somewhat diminished. He lost 10 to 15 pounds in the past year. While his right hand seems about as strong as 190 EPIDEMIC ENCEPHALITIS the left he has difficulty in using it because of an ina- bility to perform any movements quickly and without conscious effort. He first noticed that he was very clumsy in the use of this hand. He could not get it in his pocket as easily as formerly. Writing was so laborious it was impossible for practical purposes. The same condition is present to a less degree in the right leg. This is noticed in walking, climbing stairs and in getting in and out of bed. There is no pain except at times, usually at night, when the fingers become numb and slightly painful. The left extremities are normal. Since his illness ten months ago he has been slightly more sleepy, not nearly so lively and active, and is generally weaker. He looks straight ahead or watches his feet in walking. PHYSICAL EXAMINATION General Appearance: A young adult man fairly well nourished, lying quietly in bed without signs of acute or chronic illness. There is a lack of expression in his face and a slight flattening of the right naso-labial groove. Skin is dry, cool and soft. Lymph Nodes: Not pathologically enlarged. Head: Long, narrow type; symmetrical. Eyes: Pupillary reactions normal. Conjunctivae clear; no petechiae. Ears and Nose: Negative to external examination. No marked defect in hearing. Mouth: The tongue is clean and moist, it deviates to the right. There is a tremor of the tongue. Teeth: Carious lower left molar root. Face: The right face is slightly flattened. No evident paralysis. STUDIES OF SELECTED CASES 191 Throat: The uvula is in the midline. Slight conges- tion. No obvious tonsillar disease. Neck: No stiffness; no paralysis. Fig. 40.— Case VIII. Weakness of Right Half of Tongue. Chest: Fairly well developed. Expansion equal and good. Lungs: Clear and resonant throughout. Heart: Not enlarged to percussion. No point of 192 EPIDEMIC ENCEPHALITIS Fig. 41. — Case VIII. Mask-like Face and Characteristic Posi- tion of Arm. STUDIES OF SELECTED CASES 193 maximum pulsation at apex. Sounds are regular and of fair quality. No murmurs. Blood pressure 125-85. Pulse is regular, average rate, moderate volume and tension. Vessel wall not felt. Abdomen: Considerable muscular spasm. No masses or viscera felt. Superficial abdominal reflexes present. NEUROLOGICAL EXAMINATION: DECEMBER 3, 1919 Voluntary Motor System. Abnormal Attitudes and Deformities. On standing there is evidenced little that is abnormal except that the right hand and arm are held rigidly in one position. The forearm is flexed, the hand extended at the wrist, the fingers partially flexed at the metacarpo-phalangeal joint. There is a distinct, wax-like immobility of the features and a flat- tening of the naso-labial furrows. The head is inclined slightly forward and the neck held stiffly. On looking to the side, turning of the head is avoided, the body as a whole being moved instead. Gait. There is little objective alteration, though the patient complains of a stiffness and a dragging of the right leg. A slight clumsiness is noted in the swinging of this leg as he quickly turns to the right. He is able to walk on his toes or heels, sideways or backwards, without cHfficulty. Coordination, There is no swaying on standing with feet together or on the left foot alone with the eyes closed. There is some unsteadiness, however, on stand- ing on the right foot. The finger-to-nose, pointing and past pointing and heel-to-knee movements are carried out with normal precision, though the movements of the right hand are deliberate. Skilled A ds. There is no dyspraxia or aphasia. Speech is usually slow. There is a definite hesitation as he starts 13 194 EPIDEMIC ENCEPHALITIS to speak and then the words come rather slowly, but occasionally are shot out explosively, "all in a bunch," as he expresses it. The voice is soft, dull and monotonous. Reflexes: Deep Right Left Jaw 2 2 Pectoral 2 2 Biceps 3 2 Triceps 3 2 Radial 3 2 Ulnar 3 2- Patellar 3 2 Achilles 2 2 Superficial Ciliospinal Presen t Present Supra-umbilical 2 2 Suprapubic 2 2 Upper lateral abdominal 2 2 Lower lateral abdominal 2 2 Plantar flexion Present Present Babinski and modifications Absent Alisent Abnormal Involu7itary Movements. There are no ab- normal involuntary movements except when he endeav- ors to perform active movements with the right hand, when there is a motlerate, coarse, and slow interphal- angeal trembling. Muscle Sirerigth. The strength of opposed and un- opposed symmetrical movements seems about equal on the two sides. The grip in the right hand is possibly a little less than in the left. All movements of the right forearm, hand and fingers are carried out slowly. There is extreme retardation and absence of some of the finer finger movements. Complete extension of the fingers is difficult. Hyper-extension and full abduction are im- possible. It is very hard for him to pick up a coin from a table unless he gets his finger-nails under it. Writing is so slow that it is impossible for practical purposes, and STUDIES OF SELECTED CASES 195 he has learned to write with the left hand. On attempting to carry out opposed movements alternately, as supina- tion and pronation of the forearm on the right side there is decided sluggishness and incompleteness of movement. Retardation is present in the right leg, but to a much less degree. He notes an inability to move this leg as freely as the other in getting in and out of bed. He cannot extend and flex the leg at the knee as fully and rapidly as on the left. In the right arm there is considerable resistance to passive motion, slow movements, encounter- ing the same resistance as more rapid ones. Muscle Status. Volume and contour are normal. There is slight hypertonia of the muscles of the right arm and a tendency to flexibilitas cerea. Abnormal Associated Movements. Not tested. Nerve Status. No observation. General Sensory. Touch, pain, temperature, vibra- tory, pressure, muscle tendon sense and stereognostic perception are normal. Cranial Nerves and Head. Olfactory Nerve and Nose. Smell is normal in each nostril. Optic and Oculomotor Apparatus. Visual acuity is normal in each eye. There is no perimetric contraction of either field. The eyegrounds are normal. The pupils are equal each measuring 3 millimeters. They are cen- trally placed, regular, and react actively to light and on accommodation. The palpebral fissure appears very slightly larger on the right side. There is no ptosis, stra- bismus or ocular deviation. Conjugated eye movements are normal except for a slight limitation of convergence. Nystagmus is absent. Acoustic Nerve and Ear. A watch is heard thirty inches from each ear. The Rinne test is normal. 19G EPIDEMIC ENCEPHALITIS Trigeminus Nerve and Mouth. Movements of the lower jaw are equal. The corneal reflex is present and there is no alteration in sensibility in the areas suppUed by this nerve. Facial Nerve and Face. The sense of taste is somewhat delayed on the anterior two-thirds of the tongue on each side, but shows no asymmetrical differences. There is a slight flattening of the lower portion of the face on the right side and a lagging of the right corner of the mouth on showing the teeth. Glossopharyngeus and Vagus Nerves, Pharynx and Larynx. The uvula is in the midline; the palatal re- flexes and the pharyngeal reflex are active. Swallowing, respiratory and cardiac action are normal. Hypoglossus Nerve and Tongue. On protrusion the tongue deviates to the right and its movement to the left is limited. There are no visible trophic changes. LABORATORY EXAMINATIONS AND CLINICAL NOTES: Eye Examination: December 2, 1919. (Dr. Schoen- berg) . Abduction is good in both eyes and adduction poor. He focuses with the right eye, the left eye rolling out on convergence. Optic nerves normal. There is a pale ring surrounding the optic nerve in both eyes suggestive of slight process in choroid surrounding the nerve. These rings are found in myopias in young people and consist of mild degeneration of choroid due to unknown cause, probably toxic. This patient is not myopic and the similarity to myopic changes is only mentioned as a point of comparison. Probablj^ toxic in this case. Will not interfere with vision. STUDIES OF SELECTED CASES 197 Lumhar Puncture: December 2, 1919 Pressure Not increased Amount 20 c.c. Appearance Blood-tinged Cells Numerous red cells. Count not made Globulin Negative Culture No growth Wassermarm : Alcohol antigen Negative Cholesterin antigen Negative December 5, 1919. Right pupil larger than left to-day. Blood Count: December 8, 1919. Red blood cells 5,060,000 Hemoglobin 65 per cent. White blood cells 12,000 Polymorphonuclear leucocytes. . 78 per cent. Lymphocytes 22 per cent. Urine Examination: December 2, 1919. Specific gravity 1.026 Reaction Acid Color Amber Precipitate None Albumin None Glucose None Microscopical examination Negative Temperature while in the hospital ranged from normal to 99.6°. Pulse Rate: 60—84. SUMMARY The onset was ten months ago with symptoms of an acute infection. This was followed by dullness, stupidity and somnolence. Two or three weeks later paralysis of accommodation, diminution in auditory acuity, paresis 198 EPIDEMIC ENCEPHALITIS of the right side of the tongue and face, and speech alteration appeared. There' was also stiffness, clumsiness and retardation of movements of the right arm, hand, and to a less extent, of the right leg. The somnolence, eye and ear symptoms disappeared, but the other dis- turbances have remained to the present with little alteration. The present condition is a hemilateral paralysis agitans without tremor, and paresis of the right side of the face and tongue. CHAPTER XXV CASE REPORT IX Mr. F. C. Aged twenty-one. Occupation tailor. Admitted to hospital December 15, 1919. Chief Complaint. Difficulty in walking and speech, duration, 20 months. Family History. Father is living and well, fifty years of age; mother, aged forty-nine, is also living and well. Five sisters and five brothers are living and well. No tuberculosis, Bright's disease, rheumatism, heart trouble or nevous disorders in any member of the family. Personal History. Patient is single. He was born in Italy; has lived in the United States four years. His habits of eating and sleeping are regular. He smokes 5 or 6 cigarettes a day; use of alcohol denied. Takes one cup of coffee a day; no tea or drugs of any kind. He has been in the habit of taking moderate daily exercise. His pres- ent weight is 155 pounds; best weight — two years ago — was 166 pounds. Previous Illnesses. He has always been robust and healthy. Does not remember having any contagious or infectious diseases in childhood. Four years ago he had a short febrile attack, the particulars of which he does not know. He has had no operations or injuries. Head: No headaches. Ears: No pain, difficulty in hearing or discharge. Nose: Patient is not subject to colds or catarrh. Throat: No severe attacks of tonsillitis. Teeth: Have always been kept in good condition. 199 200 EPIDEMIC ENCEPHALITIS Respiratory: He has never had pneumonia or serious respiratory disorders. Cardiac: Has never had excessive shortness of breath or swelling of the feet; no palpitation. Gastrointestinal: No symptoms of indigestion; bowels regular. Genito-Urinary: Gonorrhea and syphilis denied by name and symptom. N euro-Muscular: No disorder before the onset of the present illness. Present Illness. During the latter part of March, 19 18, while serving in the army, he became severely constipated , there being a period of two weeks in which his bowels did not move at all in spite of almost constant catharsis. Previous to this he had had about one stool a day. There was no nausea, vomiting or abdominal pain. He had little appetite and so ate practically nothing during this period. Soon after the onset of constipation he had severe headache which was present in all parts of his head, and was of a boring character. On April 6, 1918, he had fever and at this time developed diplopia, constantly seeing two images of every object at which he looked. In a day or two he became dizzy, noisy and delirious. He was confined to the guard-house where he fought with the other prisoners and made a good deal of disturb- ance. He was put to bed but had to be restrained as he was actively delirious. This condition continued for three or four days, after which time his temperature became nor- mal, his diplopia disappeared and the mental excitement ceased. At no time was he particularly drowsy, and he was never unconscious. As soon as he was allowed to get out of bed he noticed that he had difficulty in walking. His movements were slow and awkward. It was also difficult for him to feed himself, or to pick up small articles with his hands. On standing he had a tendency to fall back- STUDIES OF SELECTED CASES 201 ward, and on walking, to fall forward, which would often cause him to run forward in an endeavor to regain his balance. He often found running easier than walking. At this time there was a tremor which involved his entire body and consisted in a shaking of the whole extremity. This was made much worse by any emotional excitement. His speech was so affected that talking was slow, difficult and sometimes almost unintelligible. This condition was so marked that he was supposed to be suffering from bulbar palsy. Since the onset there has been a gradual improvement in all symptoms. His speech is still slow and monotonous but always easily understood. The tremor has practically disappeared except when his muscles are actively con- tracted — being present to some extent in his legs on standing or in his arms if he attempts to lift anything, or in any emotional excitement. He believes that he is as strong as he ever was, but it is difficult for him to do any- thing, as his movements are slow and clumsy, and a rapid succession of opposed movements impossible. He has no difficulty with thinking and believes that his mind is as clear as formerly. His appetite is good; bowels regular and he has normal sexual desire. There is no pain in any portion of his body, though he is easily fatigued on any exertion. PHYSICAL EXAMINATION General Appearance. The patient is a well developed male of twenty-one years, reclining quietly in bed in apparent comfort. Eyes: Are normal; no conjunctival inflammation or petechial spots. Nose: The septum is deviated to the left. Nostrils are clear; there is no nasal dis(!harge. Ears: Are negative to external examination. 202 EPIDEMIC ENCEPHALITIS Mouth: The throat is not congested or inflamed. Tonsils are atrophic. Teeth are in good repair. Gums show no signs of pyorrhea. The tongue is partially coated. It is protruded in the midline. There is no tremor. Neck: Is held shghtly forward with some resistance to passive movement but no limitation of active move- ments. The thyroid is not visible or palpably enlarged. There are no abnormal pulsations. Chest is symmetrical; expansion is good and equal on the two sides. Lungs: Are resonant throughout. Breaths sounds are normal; no rales. Heart: The outline is normal, the sounds of good quality both at the apex and the base. Pulse is regular; rate 76. Artery wall not palpable. Blood pressure: 120-80. Abdomen: Is symmetrical; moves normally with res- piration. There is no muscular resistance or tenderness. The liver and spleen are not felt. Extremities: The muscles are well developed. There is no tremor, edema or deformity. Superficial Lymph Nodes: Not pathologically enlarged. External Genitalia: Well developed; normal. Skin is soft and moist with no eruptions. Hair is normal with masculine type of cHstribution. Temperature 98.4°. Respiration 20. Weight Ml}^ pounds. LABORATORY EXAMINATION Blood Count: December 16, 1919. Red blood cells 5,140,000 Hemoglobin 90 per cent. White blood cells 11,800 Polymorphonuclear leucocytes 71 per cent. Small lymphocytes 21 per cent. Large lymphocytes 6 per cent. Transitionals 2 per cent. STUDIES OF SELECTED CASES 203 Throat Culture: December 16, 1919. No diphtheria organisms. Lumbar Puncture: December 16, 1919. Amount 12 c.c. Appearance Perfectly clear Pressure Normal Cells 2 lymphocytes Wassermann 2 c.c. 1 c.c. .2 c.c. .6 c.c. Alcohol antigen Neg. Neg. Neg. Neg. Cholesterin antigen . Neg. Neg. Neg. Neg. Colloidal gold OOOOOOOOOfM) Urine Examination: December 17, 1919. Specific gravity 1.032 Reaction Acid Color Amber Precipitate None Albumin None Glucose None Microscopical examination No casts, crystals or cells NEUROLOGICAL EXAMINATION: DECEMBER 18, 1919 Voluntary Motor System. Abnormal Attitudes and Deformities. The patient is sitting quietly in a chair without evident signs of pain or discomfort. The facies are absolutely expressionless; all lines and furrows from the forehead and face are obliterated. The lower eye- lids sag. The mouth is closed. On standing the head and shoulders are bent forward, the arms are slightly ab- ducted at the wrists, fingers partially closed with each thumb in contact with the terminal phalanx of the index finger. The legs are not straight but are slightly flexed at the hips and knees. Gait. On walking he starts out slowly, taking rather large steps but without lifting his feet far fi'om the floor. 204 EPIDEMIC ENCEPHALITIS Fig, 42.— Case IX. Standing Attitude; Showing Slight Tremor of Legs. Soon the steps become shorter and the gait ac- celerated . He turns around slowly, the move- ments being slow and awkward. C oordination. On standing with his feet together he has a ten- dency to fall backward. There is also moderate swaying laterally and forward, which is no more marked when the eyes are closed. Non-e quilibratory. Finger-to-nose, pointing and past pointing, heel- to-knee-and-a 1 o n g- s h i n tests are performed slowly but with normal precision. There is no dysmetria. Rapid pronation and supination of either arm is impossible. Skilled Acts. There is no dyspraxia or aphasia. The speech is slow, mono- tonous and rather feeble. Handwriting, he says, is smaller than before the illness commenced, but not affected in any other way. STUDIES OF SELECTED CASES 205 Reflexes Deep Right Left Jaw 1 1 Pectoral 2 2 Biceps 2 2 Triceps 1 1 Radial 2 2 Ulnar 1 1 Suprapatellar Absent Absent Patellar 3 3 Achilles 1 1 Superficial Supra-umbilical Present Present Suprapubic Present Present Upper lateral abdominal Present Present Lower lateral abdominal Present Present Plantar flexion Present Present Babinski and modifications Al)sent Absent Abnormal Involuntary Movements. The patient states that when he is excited or angry, a general coarse tremor is produced which affects the arms and Hmbs on both sides. In the examination none is noted in the arms, but when standing there is a fine tremor of both legs. (This is evident in the photograph.) Muscle Strength. Opposed and unopposed movements of the neck, shoulder, arm, forearm, hand, thigh, leg and foot show normal strength on each side. Muscle Status. Volume: All muscles are well de- veloped, of normal contour and consistence. The tone is increased, there being a rigidity in the muscles of all four extremities. There is resistance to passive move- ment with greater resistance in flexor muscles than in extensor. Supination of the forearm is resisted more than pronation. This resistance to passive movement is not uniform, but shows the phenomenon of cog-wheel release. There is some degree of flexibilitas cerea, tlu^ arms being 206 EPIDEMIC ENCEPHALITIS held for some time in any position in which they are placed. Ahnormal Associated Movemeyits. Not tested. Nerve Status. No observation. Fig. 43. — Case IX. Showing Mask-like Expression of Face. General Sensory. Touch, pain, temperature, vibrator}^, pressure, muscle tendon sense and stereognositic per- ception are normal. STUDIES OF SELECTED CASES 207 Cranial Nerves and Head. Olfactory Nerve and Nose. Smell is normal in each nostril. Optic and Oculamoior Apparatus. Visual acuity is normal in each eye. Perimetry, roughly tested, shows no Fig. 44. — Case IX. Showing Facial Weakness on Attempting to Smile. contraction of any field. Eyegrounds: Both discs are well outlined. There are no hemorrhages. The vessel walls appear normal. The pupils are ecjual and regular; 208 EPIDEMIC ENCEPHALITIS they react actively to light and on accommodation. The palpebral fissures are increased in size, due largely to lagging of the lower lid. The upper lid covers the upper portion of the cornea while there is a broad band of sclera visible below the lower portion of the cornea. There is also a slight eversion of the lower lids. There is no perceptible exophthalmos, enophthalmos or ptosis. Strabismus is absent. There is no nystagmus. Acoustic Nerve and Ear. Hearing is normal in each ear. Air conduction is greater than bone. Trigeminus Nerve and Mouth. Movements of the jaw are normal in all directions. The corneal reflex is present. There is no ansesthesia in the region supplied by the 5th nerve. Facial Nerve and Face. There is weakness of the face on each side, more marked on the left, retraction of the mouth being much less on this side. Both eyes can be closed tightly. Taste on the anterior portion of the tongue is normal. Glossopharyngeus and Vagus Nerves, Pharynx and Larynx. The tip of the uvula deviates to the left, but the palatal arches are symmetrical and move normally during phonation. The palatal and pharyngeal reflexes are active. There is no difficulty in swallowing. Spinal Accessory Nerve. There is no sign of weakness of either sternomastoid or trapezius muscles. Hypoglossus Nerve and Tongue. The tongue is pro- truded in the midline. Its movements in all directions are equal. The trophic status is normal. SUMMARY The onset was twenty months ago with obstipation for two weeks followed suddcaily by fever, diplopia, excitement STUDIES OF SELECTED CASES 209 and delirium. These symptoms disappeared in three to four days, and then his movements were slow and awkward and speech so difficult that it was at times unintelligible. Since this time there has been a gradual improvement in ease of movement and in his voice. Examination at present shows a typical Parkinson syndrome, without the tremor, and a facial diplegia. The case is of especial interest because it is, I believe, the only case reported to date of long duration, the symptoms continuing for nearly two years. CHAPTER XXVI CASE REPORT X J. W. W., born in Scotland. Aged forty-three, mar- ried. Occupation: Electrical engineer. Admitted to the hospital April 4, 1919. Chief Complaint. Trembling of the limbs and con- tinuous sleeping for three and a half months. Family History. Mother living, but of feeble health, aged eighty. Father died at the age of fifty from cancer of the rectum. Four brothers and five sisters all living and well. No history of tuberculosis or other chronic diseases in the family. Past History. Patient has always been well. He is subject to headaches, never very severe. He has had no gastrointestinal disturbances. He denies venereal diseases by name and symptom. Last October he had influenza, but made a good recovery. He has always been active and of a rather nervous temperament. He does not remember any acute infectious diseases in childhood. Personal History. Patient is an electrician and inventor. He is married; his wife is living and well. He had two children; one died through instrumental labor. His wife had one abortion during an attack of pneumonia. He eats his meals regularl}^, but sleeps very irregularly, often sleeping but a few hours at night, as he is in the habit of working late over inventions. He denies the use of alcoholic stimulants. He smokes about six pipes of tol)acco a day. He has never used any drugs. 210 STUDIES OF SELECTED CASES 211 Present Illness. Three and a half months ago he began to be very nervous and irritable. At the same time he developed a tremor of his hands. His ears pained him for a week; this was followed by severe headache lasting two or three days. He stopped work and his physician ordered him to go to l)ed. The first night he could not sleep. The next night he fell asleep and for three weeks he slept almost all the time. It was possible to arouse him enough to take food, but he would frequently fall asleep while taking it or while being bathed. For the first two weeks he talked continuously during his sleep. When arou.sed he seemed rational, but his talk during his sleep was entirely irrational. During the weeks he was sleep- ing he had a constant fever, at times as high as 104°. He had no vomiting or convulsions. His neck was not stiff. He had no paralyses of any muscles. After a time he gradually grew better, got up and seemed fairlv well. He was not nervous or irritable, but somewhat indifferent to what was going on about him. Two weeks ago his left arm began to twitch, with no particular movement, but flexion of the forearm was more frequent than smy other. A few daj's later he began to have irregular movements of his head. At this time his left leg seemed weak. He could lift it but dragged it in walking. Soon the left leg also began the same irregular involuntary movements as in the arm and head. About this time the left upper eyelid drooped and he was unable to lift it. During the last four or five days the right eyelid has become the same as the left. There have never been any convulsive movements in the right arm or leg, while the movements of the left side have steadily grown worse; that is, they are almost constantly present when he is awake, but are made worse bj^ excitement, and at some 212 EPIDEMIC ENCEPHALITIS A Series of Photographs Illustrating the Progressive Phases of Movement and Facial Expression through WHICH the Patient is Constantly Passing Fig. 45. — Case X. No. 1. Fig. -IG.— Case X. No. 2. STUDIES OF SELECTED CASES 213 I'iG. 47— Case X. No. ;j. FiQ. 48.— Case X. No. 4. 214 EPIDEMIC ENCEPHALITIS times of the day they seem worse than at others. His speech was normal until three weeks ago when a slight ''slur" was noted. During the last few days he feels that Fig. 49.— Cask X. No. 5. his speech is more involved, but it seems to him to be more as though he did not have the strength to talk. At times during the last two weeks he has been irrational and seems to be steadily growing moi-e stuporous. He STUDIES OF SELECTED CASES 215 has had no incontinence of urine or feces. His appetite seems good. Fig. 50. — Case X. No. 6. Two weeks before admission he had an eruption around the waist Hne which he calls "hives." The eruption appeared in streaks and was accompanied by itching. It disappeared in a few days. 216 EPIDEMIC ENCEPHALITIS GENERAL PHYSICAL EXAMINATION General Appearance. A middle-aged man, well de- veloped and nourished, lying dorsally in bed with his Fig. 51. — Case X. 2so. 7. eyes closed. He does not appear to be in pain. At frequent intervals there is a spasmodic movement of the left arm, head and left leg. The left forearm is flexed on the STUDIES OF SELECTED CASES 217 arm. The left hand is tightly closed. His speech is rather indistinct. His mouth appears drawn to the left when smiling. 52.— Case X. Head is well shaped. There are no tender areas over the skull, mastoid or sinuses. The neck is not stiff. The eyes are both closed; the patient is unable to open the left eye but can raise the right lid about half way. The 218 EPIDEMIC ENCEPHALITIS pupils are slightly dilated, clear and regular. They react very sluggishly to light. There is a marked nystagmus to the left. The fundi appear normal. The nose is negative to external examination; there is no discharge. The ears are negative; the ear drums appear normal. Mouth: The lips are not cyanotic. The tongue is heavily coated. The teeth in the upper jaw are false; in the lower jaw they are poor. There is a moderate pj^orrhea. Throat. The tonsils are not enlarged or inflamed. Thorax is well developed; expansion is equal on the two sides and symmetrical. Fig. 53. — Case X. General Position U?ually Assumed. Head Thrown Back and Inclined to the Left. Left Arm Flexed and Left Hand Closed. Permanent Dorsal Flexion of the Toes on the Right Side. *S'^-m. The axillary region of the left side seems more wrinkled and lax than on the right. Lungs. Resonance is normal throughout; there is no alteration in breath or voice sounds. No rales are heard. Heart. The apex is not seen or definitely felt. The heart outline is normal, the left limit of dullness being 10 cm. to the left of the mid-line in the fifth interspace. There are no murmurs. The action is regular. Rate 100. The pulse is of good ciuality. Blood pressure 114 — 75. Abdomen. There are no areas of tenderness. The liver dullness extends from the fourth interspace to the costal STUDIES OF SELECTED CASES 210 margin. The liver edge is just palpable. The whole abdomen is held rather rigidly, but there is no localized muscular spasm. External Genitalia appear normal. Superficial Lymph Nodes are not pathologically enlarged. Extremities. The left arm is held rather spastically flexed at the elbow. The left leg is slightly spastic. There is tenderness on deep pressure over the muscles of the left calf and the left forearm. There is some hyperesthesia over the left forearm. Blood Examination: April IG, 1919. Red blood cells 5,300,000 Hemoglobin 70 per cent. White blood cells 15,800 Polymorphonuclear leucocytes. . 8G per cent. Large lymphocytes 6 per cent. Small lymphocytes 6 per cent. Transitionals 1 per cent. Eosinophiles 1 per cent. Blood Wassermann: April 17, 1919. Alcohol antigen Negative Cholesterin antigen Negative Blood Culture: April 17, 1919. No growth Spinal Fluid: April 17, 1919. Amount 15 c.c. Appearance Clear, colorless Pressure Normal Globulin Trace Lymphocytes 260 (the interne who made this count does not believe it is correct) Culture Negative Wassermann 2 c.c. 1 c.c. .6 c.c. .2 c.c. Alcohol Neg. Neg. Neg. Neg. Cholesterin Neg. Neg. Neg. Neg. 220 EPIDEMIC ENCEPHALITIS Blood Examination: April 21, 1919. White blood cells 13,200 Polyraorphonuclear leucocytes 74 per cent Large lymphocytes 7 per cent Small Ij'mphocj^tes 18 per cent Transitionals 1 per cent Spinal Fluid: April 21, 1919. Pressure Apparently decreased Amount 10 c.c. Appearance Slightly blood tinged Globulin Present Cell count • 23 lymphocytes Colloidal gold curve 1, 2, 2, 3, 4, 3, 2, 1, 0, Ui'ine Examination: April 22, 1919. Specific gravity 1.029 Reaction Acid Color Dark amber Turbidity None Precipitate Slight flocculent Albumin None Glucose None Microscopical exam Many amorphous urates Blood Examination: May 5, 1919. White blood cells 14,600 Polymorphonuclear leucocytes 73 per cent. Large lymphocytes 9 per cent. Small lymphocytes 17 per cent. Transitionals 1 per cent. NEUROLOGICAL EXAMINATION: APRIL 16, 1919 Voluntary Motor System. Attitudes. The patient is lying dorsally in bed; his head is thrown back and inclined to the left. Both eyes are closed; the left one appears more tightly shut than the right. His mouth is drawn over to the left side. The head is not held still STUDIES OF SELECTED CASES 221 but'is rotated from side to side as though he were trying to bore a hole in the pillow. His left arm is flexed at the elbow and the fist is firmly clenched. The arm is con- stantly moved about, but the flexed position is generally maintained. The left leg is drawn up; the thigh is flexed at the hip and the leg at the knee. The limb is also in almost constant motion, being moved about in all direc- tions. The right side of the face is somewhat flattened; the right arm and leg are usually extended and are moved about somewhat, but are not in as continuous motion as are the extremities of the left side. It is possible for him to hold his hmbs and head quiet for about thirty seconds if he makes a strong effort, but he is unable to inhibit the movement for a longer period. He is able to open the right eye to about half the normal extent, but cannot open the left one at all. Both eyes are drawn over to the left and there is nystagmus to that side. The mouth is drawn over more to the left and he is constantly making grimacing expressions which vary from a pouting of his lips, a roll- ing of his lower lip, to a forced smile. At other times there is a period of uncontrollable laughter. Forcible attempts passively to open his left hand and to extend his left arm are painful. Gait. The patient is unable to stand or walk. Coordination. Finger-to-nose and heel-to-knee tests on the right side are well performed. On the left side the hand cannot be opened, so he attempts to touch the end of his nose with his knuckle. This is accomplished by coarse, irregular, rotary movements which end after considerable difficulty in placing the knuckle accurately on the tip of the nose. The incoordination becomes less as the hand nears the nose. The heel-to-knee test is carried out with the same difficulty on the left side, but in the end is accomplished with fair ])r(!cisi()M. Thcie is a 222 EPIDEMIC ENCEPHALITIS marked retardation of successive movements of prona- tion and supination on the left side; but they are normal on the right. Skilled Acts. He is able to salute perfectly with the right hand and makes a fairly normal attempt to do so with the left arm, though the fist is closed and it is accom- panied by jerky movements. Speech is slightly slurred. Reflexes: Deep Right Left Jaw 1 1 Pectoral 1 1 Biceps 2 1 Triceps 2 1 Wrist 1 1 Radial 1 1 Ulnar 1 1 Patellar 3 1 Suprapatellar 3 1 Achilles 3 1 Superficial Ciliospinal Absent Absent Supra-umbilical Present Present Suprapubic Present Present Upper lateral abdominal Present Present Lower lateral abdominal Present Present Plantar flexion Absent Present Babinski Present Absent Chaddock Present Absent Oppenheim Present Absent Gordon Present Absent Schafer Present Absent There is transient patellar and ankle clonus on the right side. Abnormal Involuntary Movements. These have been described under the head of general appearance and con- sist of a choreo-athetosis which is limited to the left side and most marked in the head, face and arm. STUDIES OF SELECTED CASES 223 Muscle Strength. This is rather difficult to tost on account of the constant movement of the left side, but there seems to be no definite loss of strength on either side. Muscle Status. There is no apparent loss in volume or change in contour of any portion of the body (except for the flattening of the right side of the face) . Abnormal Associated Movements. None are present. Nerve Status. Nothing abnormal noted. General Sensory. Pain, temperature, vibratory, muscle-tendon sense and stereognostic perception are all normal. There is some hyperaesthesia over the left fore- arm and hand and distinct tenderness on deep pressure over the muscles of the left forearm, left thigh and calf. Subjective Sensibility. He complains of severe burning pains in the left forearm and hand which are present most of the time. Passive extension of the fingers or force- ful extension of the left wrist cause him to cry out with pain. Cranial Nerves and Head. Olfactory Nerve and Nose. Normal. Optic and Oculomotor Apparatus. Visual acuity cannot be accurately estimated. Perimetry, roughly tested, seems normal. (The patient was seen by Dr. Tilney before his admission to the hospital and at that time had a left homonymous hemianopsia.) Eyegrounds: Both optic disks are normal; there are no hemorrhages. The pupils are moderately contracted, regular, equal; reac- tion to light and on accommodation is limited. The left eye is entirely closed; the right one is often closed but may be opened about half way. There is no evident exophthalmos or enophthalmos. There is a deviation of both eyes to the left and a limitation in his ability to move them to the right. There is a moderate horizontal nystagmus with a slow movement to the left. 224 EPIDEMIC ENCEPHALITIS Acoustic Nerve and Ear. The hearing is normal on both sides. Air conduction is greater than bone on each side. Trigeminus Nerve and Mouth. The jaw reflexes are normal. Both conjunctival reflexes are present. There is no evident weakness of any of the muscles of mastication. Facial Nerves and Face. Taste on the anterior two- thirds of the tongue is normal. There is a slight flattening of the lower portion of the face on the right side. The Glossopharyngeus, Vagus Nerve, Pharynx and Larynx. The uvula is in the median position. The palatal and pharyngeal reflexes are normal. The quality of the voice is normal. There is no difficulty in swallowing. Spinal Accessory Nerve. There is no evident weakness of either sternomastoid or trapezius muscle. The Hypoglossus Nerve and Tongue.' The tongue is protruded in the mid-line, and there is no trophic dis- turbance, tremor or twitching. Mentally he is at present surprisingly clear and bright, answering questions promptly and correctly and showing a keen sense of humor. At times he has delusions, believing his attendants are trying to starve him and not wanting him to have water or to see his wife. Occasionally at night he is quite delirious, talking loudly and incoherently and attempting to get out of bed. He is perfectly oriented, but his memory for recent events is quite faulty. There is marked emotional instability resulting in uncontrollable laughter or crying. He shows interest in the condition of the patients in the beds next to his, and cried at the sight of one of these patients greeting his wife. He is surprisingly indifl"erent to his own condition and if questioned about it expresses the feeling that he will entirely recover. The constant movement and contortion of his head, arm and leg do not seem to tire or distress him very nuich. STUDIES OF SELECTED CASES 225 SPECIAL EXAMINATIONS AND CLINICAL NOTES Eye examination, April 18, 1919 (bj-^ Dr. Schoenberg) : 1. The patient keeps both eyes closed. If told to open them he does so, but shows a slight ptosis on the right and a marked ptosis on the left. 2. Position of the eyes is that of conjugate deviation to the left of an irritative nature. Motility is good up, down and to the left; slightly insufficient to the right. There is slight insufficiency of convergence. 3. Pupils dilate to dark, but the reaction to light and on accommodation is very much reduced. 4. Corneal sensibility is normal. 5. Fundi normal. 6. Vision cannot be taken on account of the patient's general condition. Eye examination, April 22, 1919 (by Dr. Schoenberg): 1. Vision is about 10/15 in the right eye; 10/30 in the left. 2. Patient observes color — red and green — in each eye. 3. Conjugate deviation to the left has disappeared but there is still slight difficulty in looking to the right. 4. There is marked insufficiency of convergence. 5. Fields of vision roughly taken are normal. No hemianopsia. April 22, 1919. Since the patient has been in the hos- pital he has been irrational the greater part of the time. He has delusions, especially in regard to the medical attendants, believing that they are persecuting him and do not wish him to get well. Two days ago he would not remain in bed and had to be restrained. Yesterday he seemed more normal and easier to manage, but to-day he is quite obstinate and refuses all forms of medication. The symptoms have remained practically the same for 15 226 EPIDEMIC ENCEPHALITIS the past few days, the temperature ranging from 100° to 101°. He has complained of no pain. He had to be catheterized once. The choreo-athetotic movements of the head, left arm and leg continue. These are more vio- lent when he becomes excited, and disappear entirely when he is asleep. Occasionally when drowsy he shows signs of catatonia holding his arms in the air and his mouth open and remaining in this position for several minutes. He is now able to open both eyes to some extent, the right more than the left. April 25, 1919. The movements of the left side continue without apparent change. Mentally he is much clearer and more reasonable. At times he has a good deal of pain in the left arm and leg. He is now able to open both eyes fully, though he very often keeps the left one en- tirely closed and the right one partly so. May 5, 1919. The patient has been sitting up in a chair for about one-half hour at a time for the past few days. In general, he seems somewhat better. Often his movements are not as violent as before, but they are made worse by any excitement. He has a distinct an- tipathy to popular music and if it is played on the pho- nograph in the ward he becomes verj' excited. He enjoys classical music, and if it has any effect upon him it is a quieting one. May 15, 1919. The patient has improved very much since the lastnote. He is almost constantly entirely ration- al. At night he sleeps well, is quiet and has no delirium. The movements of the left side are much less violent and it is possible for him to inhibit them entirely by a strong effort for a period of about two minutes. He is able to extend the fingers of his left hand fully except for the little finger which remains partially flexed. Dysaes- STUDIES OF SELECTED CASES 227 thesia is present on the left side but is not as pronounced and troublesome as formerly. There is no ptosis on either side. The nystagmus has disappeared and the pupillary reactions are normal. He is able to read the larger print in the newspaper, but finds that the focal distance for small print is about double what it was before his illness commenced. The visual fields are not contracted. The weakness of the right side of his face is difficult to demon- strate and has practicality disappeared. The patellar and Achilles reflexes on the right side remain active, and the Babinski and its modifications are still present, though his great toe is no longer constantly in the positioii of dorsal flexion. The left hemiataxia is still marked. January 10, 1920. During the past seven months there has been a slow but steady improvement. The movement of the head and arm still continues, but less violently. The head is held nearly erect, but during the movement it is drawn more to the left side than to the right. The facial grimacing has almost entirely disappeared, though at times there is a tendency to protrude and evert the lower lip. There is a rhythmical forward and backward movement of the tongue. The tip is not protruded from the mouth but is pressed against the lower teeth and the tongue everted so that the dorsum strikes against the upper teeth. This does not interfere with speech as is ceases with voluntary movement. Difficultj^ in swallow- ing is present to some extent, but is due to a drynest of the throat rather than to any motor weakness. Unless the left arm is voluntarily placed in some other position, it is held with the elbow sharply flexed, the wrist flexed and the fingers closed, the hand being pressed against the chest in the pectoral region. It is possible to open the hand fully and hold it open for a minute or two, but as soon as the voluntary' effort ceases, it closes again 228 EPIDEMIC ENCEPHALITIS tightly. Passive extension of the fingers is no longer painful. Walking is accomplished without difficulty, and the patient frequently takes walks of a mile or more. There is a tendency to toe in with the left foot which is more pronounced when he is fatigued. While he is walking the movement of the arm and head is lessened. On sitting down, if one knee is crossed over the other there is a rhythmical dorsal flexion of the foot. This is present on both sides but is more pronounced on the left. To stop it he frequently sits with his thighs abducted, his feet inverted, and the outer margin of the right foot on the inner side of the left one. His vision now is normal, paralysis of accommodation having completely disappeared. The treatment he has received has been entirely symptomatic, consisting of sedatives administered at irregular intervals as required. Chloral hydrate and paraldehyde have been more quieting than bromides or drugs of the veronal series. SUMMARY The salient points in the history are the gradual onset of an illness characterized by marked stupor, somnolence, delirium and fever, later by choreo-athetotic movements of the left arm, burning, prickling sensations in the left arm and leg, weakness of the left leg, ptosis of the left eye, involuntary movements of the head and left side of the face, ptosis of the right eye, involuntary movements of the left leg; then lessening of the ptosis in the right and then in the left eye, return of normal strength in the left leg, improvement of mental state, diminution in violence of choreo-athetotic movements. The important findings on neurological examination STUDIES OF SELECTED CASES 229 were: choreo-athetotic movements of the left side, most marked in the head, face and arm, normal reflexes on the left, increased reflexes on the right, with a positive Babinski and ankle clonus; bilateral ptosis most marked on the left, slight weakness of the lower portion of the face on the right, conjugate deviation of the eyes to the left, nystagmus to the left, slight diminution in ocular movements to the right, pupils which reacted sluggishly to light and on accommodation, probablj- a left homony- mous hemianopsia, ataxia of the left arm and leg. In consideration of the history of prolonged somno- lence, lethargy and transient cranial nerve palsies, together with the spinal fluid findings, the clinical con- dition seems to be quite clearly epidemic encephalitis. The neurological findings cannot be explained on the basis of a single lesion, but the predominating signs seem to conform closelj^ enough to the thalamic syndrome to allow of a diagnosis of a lesion of the right optic thalamus. The accepted signs of a thalamic lesion are unilateral pain, anaesthesia (deep, and frequentl}^ superficial), ataxia, astereognosis, choreo-athetoid movements. Other findings from involvement of neighboring structures include hemiplegia, hemianopsia, disturbances of ocular movements and of the pupillary reflexes. In this patient dysaesthesia and pain were present. Hemianaesthesia was not present, at least during his stay in the hospital, there being a moderate hyperaes- thesia to touch over the left forearm and hand and pain on pressure over the left forearm and calf. There was no astereognosis, the patient recognizing the size, shape, consistence and surface characteristics of objects placed in either hand. He was also able to reproduce with his right hand smy position in which his left hand and fingers were placed. Ataxia and choreo-athetoid movements were 230 EPIDEMIC ENCEPHALITIS present. There were disturbances of the ocular move- ments and pupillary reactions, and before he entered the hospital weakness of the left leg and a left homonymous hemianopsia. The increased deep reflexes and Babinski on the right side must of course be due to a separate lesion in the corresponding pyramidal tract. CHAPTER XXVII CASE REPORT XI Mr. A. AI. Aged fifty. Married. Iron-inolder. Admitted to the hospital March 6, 1920. ChieJ Complaints. Drowsiness, fever, twitchings of the muscles of the abdomen and legs; duration two weeks. Personal History. Patient has always been strong and healthy; does not remember any of the diseases of childhood. He is not subject to respiratory infections, and has had no nervous disorders of any kind. Present Illness. The onset was two weeks before ad- mission at which time he had a bad cold in the head and fever. This was so severe that he stopped work and went to bed. There was some aching in his head, back and legs. He was examined by a physician who told him that he had influenza. Three days after the onset he noted a twitching of the muscles of the left leg; within a few hours the right leg, the right arm and then the muscles of the entire body were involved. The twitching was likened to short electrical shocks occurring in all portions of his body involving his face and tongue as well as the muscles of the trunk and extremities, so that it was prac- tically impossible for him to talk or to swallow. Attempts to hold his arms or legs rigidly, if resulting in any effort, possibly increased the severity of the contractions. This generalized twitching lasted about three days and then stopped to a large extent in the face, upper extremities, upper portion of the trunk and back. The twitching in the abdominal muscles and in the lower limbs, however, 231 232 EPIDEMIC ENCEPHALITIS has continued with the same intensity up to the present time. There have also been fever, sweating, dryness of the membranes of the nose and throat, anorexia, labored stammering speech, difficulty in swallowing and in urina- tion. There were no paralyses of the extremities, although his limbs felt weak and trembly and he was unable to walk. His family noticed that his eyes watered and his eyelids drooped. At present he has no pain; he feels drowsy and tired, but is not disturbed by the muscular contractions in the abdomen and legs. PHYSICAL EXAMINATION General appearance is that of a middle-aged man, acutely ill, flushed and sweating. There are sudden, jerky, spasmodic, twitching movements most marked in the abdominal muscles and, to a less extent, in the lower limbs. The skin is flushed and moist. Over the sternum there are a few very small red spots which re- semble petechiae. Head. No deformity or sinus tenderness. Eyes. The lids blink frequently and are held partially closed. There is slight double ptosis; the upper lids cannot be elevated enough to expose the sclera above the iris. The small blood vessles of the conjunctiva are injected. Eyegrounds: The discs are normal, sharply outlined, the vessels slightly tortuous. There are no hemorrhages. Nose. No evident discharge or signs of inflammation. Ears. No mastoid tenderness. The right drum is distinctly thickened along the site of the malleus, almost obscuring that bone. There is no redness or bulging. In the left drum the landmarks are visible. There is some redness in Shrapnell's membrane. Mouth. There is a slight tremor of the tongue and lips. The teeth are dirty. One lower right molar is carious. STUDIES OF SELECTED CASES 233 There is a peculiar mottled erosion of the roof of the mouth on the right side which is covered with a slight whitish exudate. The soft palate is symmetrical and moves with swallowing. The left tonsil is larger than the right; both appear reddened. Neck. No rigidity. The thyroid is not palpable. No abnormal pulsations. Heart. Outline normal. Apex not palpable, action regu- lar. The sounds are of normal character at the apex and base; no murmurs. Pulse 96. Blood pressure lGO-90. Lungs are clear and resonant throughout. Respiration is jerky due to the contractions of the abdominal muscles. Abdomen is soft. There is a full, rounded mass above the symphysis pubis which seems to be a distended blad- der. The liver and spleen are not felt or enlarged to percussion. No rose spots. Extremities. There is no deformity or edema; no spasticity or tendency to catatonia. Superficial Lymph Nodes are nowhere enlarged. Rectal Examination. No hemorrhoids. Prostate is small; no masses. Temperature on admission to the hospital was 103.2. Respirations 22. NEUROLOGICAL EXAMINATION: MARCH 16, 1920 Voluntary Motor System. Abnormal Attitudes and Deformities. The patient is lying on his left side in bed with eyes closed, apparently asleep. His face and fore- head are moist with perspiration and he has an expression- less appearance which is not unlike that seen in typhoid fever. The mouth is closed and respiration is not labored. Color is good and there is neither cyanosis nor jaundice. He is easily aroused and when so is alert, talking easily 234 EPIDEMIC ENCEPHALITIS and without hesitation, being perfectly rational. There is a slight lateral movement of the trunk due to the spasmodic contraction of the abdominal muscles. Gait. Not tested. Coordination. Equilibratory not tested. Non-equi- libratory: Finger-to-nose, pointing and past-pointing tests of the upper extremities show normal precision of move- ment. Heel-to-knee tests are not performed so well, the heel on each side being placed above the opposite knee, and moved downward along the skin in a rather jerky, irregular manner. There is no dysmetria or adiadochoki- nesis. • Skilled Acts. The voice is weak, the speech stammer- ing, though the patient states that it has improved much since the onset when he was practically unable to speak intelligibly. There is no dyspraxia. Reflexes: Deep Right Left Jaw 2 2 Pectoral.. 2 2 Biceps 2 2 Triceps 1 1 Radial 2 2 Ulnar 1 1 Wrist 1 1 Suprapatellar Patellar 2 2 Achilles 2 2 Periosteal uncrossed Absent Absentj "- Superficial Supra-umbilical Absent Absent Suprapubic Absent Absent Upper lateral abdominal Absent Absent Lower lateral abdominal Absent Absent Cremasteric Present Present Plantar flexion Absent Absent Babinski and modifications Absent Absent STUDIES OF SELECTED CASES 235 Abnormal Involuntary Movements. There are repeated sudden clonic contractions of the abdominal muscles which are at times rhythmical and alternating, occurring first on one side of the abdomen and then on the other. On the right side the umbilicus is moved outward as though the contraction were of the transversalis, while on the left side it is elevated and moved outward as though due to contraction of the external oblique. The contractions are separated by varying intervals and are >^^:mL^mBm Fig. .'54.— Case XI. General Appeaiaiue. Lethargy. Constant State of not continuous. When occurring most rapidly there are about 30 to the minute. Similar twitchings are also present in the muscles of the leg, though they are more irregular and seem to involve a greater number of muscles. At times slight twitchings are seen in the muscles of the arms and also the face especially involving the muscles in the neighborhood of the mouth. These are of much less frequent occurrence than those in the legs and abdomen. Not more than a single muscle is affected 236 EPIDEMIC ENCEPHALITIS Fig. 55. — Case XI. Shaded Area — Hypsesthesia, Hypaljj;esia Thermohypesthesia. STUDIES OF SELECTED CASES 237 by each contraction, and at times it is apparently limited to a portion of one muscle. Active movements and efforts to control the twitching are said by the patient to make it worse, but on his attempting to sit up, con- traction of the abdominal muscles seems to inhibit the twitching. There are no tremors, choreiform or athetoid movements. Muscle Strength. The patient is able to rise from the recumbent to the sitting position. No attempt was made to make him get out of bed. Opposed and un- opposed movements of the neck, upper extremities and trunk do not show any special weakness. It is diffi- cult for him to hold either lower limb above the bed for any length of time. He has a subjective sense of weakness in both legs and there seems to be a general diminution in strength which is not more marked on one side than on the other and does not involve any particular muscle group. Muscle Status. The volume and contour are normal. The muscles are soft and of normal tone. There is a slight increased irritability, light percussion causing contrac- tion of a few muscle fibers in almost any of the larger muscles of the trunk or extremities. Myoidema is present in both deltoids. Abnormal Associated Movements. No observation. Nerve Status. Irritability: Trousseau's sign negative; Chvostek's sign negative. General Sensory. Sense of touch is diminished over both legs and lower abdomen and back. Cotton is per- ceived everywhere but there is a good deal of uncertainty about it on both legs below the knee. Localization below the knee is very difficult and discrimination between sharp and dull over both limbs is uncertain. There is hypaesthesia over this area and difficulty in discriminat- 238 EPIDEMIC ENCEPHALITIS ing between cool and warm temperatures. Vibratory, pressure, muscle tendon sense and stereognostic percep- tion are normal. Cranial Nerves and Head. Olfactory Nerve and Nose. The odor of menthol is perceived in each nostril. Optic and Oculomotor Apparatus. Visual acuity is not accurately tested, but the patient states that he cannot see quite so clearly as before the illness commenced. Perimetry, roughl}^ tested, is normal. The pupils are of medium size, equal, regular, reacting actively to light and on accommodation. The palpebral fissures each measure 7 millimeters. There is no exophthalmos or enophthalmos. There is partial bilateral ptosis, he is unable to uncover more than half of the iris above the pupil. There is no strabismus or other ocular deviation. The conjugated eye movements are normal. Nystagmus is absent. Acoustic Nerve and Ear. A watch is heard three inches from the right ear and eighteen inches from the left. Bone conduction is greater than air on the right side, and normal on the left. Trigeminus Nerve and Mouth. Voluntary movement of the jaw is normal in all directions. Corneal sensibility is practically absent on the right side and diminished on the left. Facial Nerve and Face. Movements of both sides oj the face are equal and symmetrical, but there is a smoothed-out appearance of the lower face and an inflexibility of the oral musculature so that there is no free play of emotional expression. Glossopharyngeus and Vagus Nerves, Pharynx and Larynx. The uvula is in the midline. The palatal re- flexes and pharyngeal reflex are present. Swallowing, respiratory and cardiac action are normal. STUDIES OF SELECTED CASES 239 Spinal Accessory Nerve. Both sternomastoid and trapezius musclos contract normally. Hypoglossus Nerve and Tongue. The position of the tongue when protruded is median and its movements in all directions are normal. There is a slifi;ht fine tremor of the tongue, but no evident fibrillary contraction. Tegumentary. There is very little hair on the chest, arms or legs, and the arrangement of the pubic hair is of the female type. Over the sacrum there are two or three small superficial decubital ulcers. Summary of Neurological Examination. The impor- tant findings on neurological examination are: 1. Lethargic state from which he is easily aroused, 2. Dysarthria and lower facial rigidity. 3. General weakness of the lower extremities. 4. Diminution of tactile, pain and temperature sense, with poor localization and discrimination over both legs and lower abdomen. 5. Sudden clonic contractions in muscles of the ab- domen and legs, and, rarely, of arms and face. LABORATORY EXAMINATIONS AND CLINICAL NOTES • Blood Wassermann, March 6, 1920. Alcohol antigen Negative Cholesterin antigen Negative Blood Culture, March 6, 1920. A long bacillus; probably a contamination. Spinal Puncture, March 6, 1920. Amount 15 c.c. Pressure Normal Appearance Clear and colorless Cells 14 lymphocytes Globulin Negative 240 EPIDEMIC ENCEPHALITIS Wassermann 2c. c. Ic.c. 6c. c. 2c.c. Alcohol antigen Neg. Neg. Neg. Neg. Cholesterin antigen . . . Neg. Neg. Neg. Neg. Colloidal gold curve 1, Ihz, 2, 2, U^, 0, 0, 0, 0, 0. Culture Sterile Throat Culture, March 7, 1920. No Klebs Loeffler bacilli. Blood Count, March 7, 1920. White blood cells 18,140 Polymorphonuclear leucocytes 79% Lymphocytes 19 % Transitionals 2 % Blood Culture, March 8, 1920. Sterile. Urine Examination, March 8, 1920. Specificgravity 1 . 032 Reaction Acid Color Dark amber Sediment Slight flocculent precipitate Albumin Trace Ghicose Absent Microscopical examination A few hyaline easts; no white blood cells. Mouth Culture, March 9, 1920. Hemolytic staphylococcus aureus and streptococcus predominate. Organisms of Vincent's angina present in smears. Blood Urea, March 10, 1920. .54 grams per litre. Phenolsulphonephthalein test, 64 per cent excreted in two hours. STUDIES OF SELECTED CASES 241 Spinal Puncture, March 11, 1920. Amount lo c.c. Pressure Slighth- increased Appearance Clear with slightly pinkish tinge Cells 5 lymphocytes Globuhn ? X-ray Examination of Teeth and Si7iuses, IMarch 10, 1920. Left frontal absent. Remaining right lower molar distinctly carious. Xo evidence of abscesses in any of the teeth. No sign of disease in accessory sinuses. Blood Uric Acid: March 12, 1920. 3.5 mg. per 100 c.c. Spinal Puncture, March 29, 1920. Amount 15 c.c. Pressure Not increased Appearance Clear, colorless Cells 20 lymphocj-tes Globulin + March 24, 1920. During the first week in the hospital the fever continued about 101°. In the second week it was about a degree lower. During the past week it has taken a slightly upward trend and to-day reached 101.4°. With the increase in fever the lethargj^ has become more marked, so that it is now not so easy to arouse him, and unless actively disturbed he is continuously in a stupor. Speech is possiblj^ a little less difficult. Sensory changes and weakness of the leg remain unaltered. The bed-sores on the back are healing. On admission there was urinary retention, later the urine was passed involuntarily, but to-day hevoided voluntarily when aroused. The muscular twitchings have remained unchanged during the period of observation. March 29, 1920. Fatal termination. 16 242 EPIDEMIC ENCEPHALITIS AUTOPSY March 30, 1920. 10 hrs. p. m. By Dr. H. E. Meleney The body is that of a well developed, somewhat em- aciated middle-aged white man measuring 174 cm. and weighing 150 lbs. There is considerable rigor mortis and moderate lividity of the dependent parts. No skin erup- tions. There are two bed sores over the sacrum. The hair on the scalp is profuse and elsewhere is of normal dis- tribution. The eyes are sunken and eye balls rather soft. The pupils are unequal, the left measuring 4 mm. and the right 5 mm. They are both circular. Conjunctivae pale; no petechise. Ears and nose are externally negative. Mouth contains small amount of bloody mucus and there is blood on the face which has apparently run out of the mouth. Teeth are dirty, there is a slight amount of pyorrhea but very little caries. Right lower molar has an abscess on its front aspect. Superficial lymph nodes not enlarged. Right testicle is smaller and softer than the left. No edema. Abdominal Cavity. Panniculus measures 2.5 cm. Fat is normal in appearance. There is extensive black discoloration of the parietal peritoneum beneath the rectus muscle on both sides and above this is a slight hemorrhage into the subperitoneal tissue. This hemor- rhage does not extend into the muscle but the muscle is slightly pale. The cavity contains no free fluid. Perito- neum is everywhere smooth and glistening. The liver ex- tends just to the costal margin. The spleen is surrounded by a few firm adhesions to the omentum and diaphragm and is high up under the costal margin. The bladder is contracted. Appendix is retro-cecal about 6 cm. in length; its distal half pale and fibrous and bound by rather firm adhesions to the mesentery of the ascending STUDIES OF SELECTED CASES 243 colon. There is much mesenteric fat. Diaphragm on right side is at the level of the fourth interspace and on the left side at the level of the fifth rib. Thoracic cavity. The left lung is not adherent ; no free fluid in the cavity. Right lung bound down laterally and posteriorly by firm fibrous adhesions; no fluid in cavit3^ Pericardial cavity contains about 25 cc. of clear, straw-colored fluid. No evidence of percarditis. Heart. Weighs 300 gms. It is very flabb}' and there is rather an extensive amount of epicardial fat. Epicardium itself is normal. The coronary arteries are not tortuous. The right auricle on its outer surface shows one small fibrous patch. Internally it is normal. The tricuspid orifice admits the tips of four fingers. The cavities are all of normal size. The mitral valve shows distinct thickening at its line of closure, particularly the anterior flap. The posterior papillary muscle shows some fibrosis and some splotches which appear like hemorrhages into the tissue. The endocardium of the left ventricle is slighth' thick- ened in irregular streaks. The aortic valve shows marked thickening of all cusps with partial calcification. There are yellow plaques in the endocardium just below the valve and in the sinuses of Valsalva and in the beginning of the aorta. The coronary arteries show a few raised yellow plaques in the first few centimeters which narrow the Imiien, but beyond these the arteries arc delicate. The mj'ocardium is everywhere pale and very flabby but shows no fibrosis and no gross fatty changes. Measurements Tricuspid valve 13 cm. Mitral valve 9.5 cm. Pulmonary valve 7.2 cm. Aortic valve 8 cm. Left ventricle 14 mm. 244 EPIDEMIC ENCEPHALITIS Right ventricle 4 mm. Aorta has a few fiat yellow plaques throughout its course and in the arch two raised white plaques in which the intima is greatly thickened over a thick fatty plaque between it and the media. It is normally elastic. Lejt lung weighs 560 gms. It does not collapse but crepitates throughout most of its surface. It is reddish- blue with much anthracosis. On the lateral aspect of the lower lobe is a stony hard nodule about 1.5 cm. in diame- ter, part of the surface of which is white in color. On sec- tion the entire lung is greatly congested exuding a large amount of bloody frothy fluid. It is apparentl^^ quite edematous and emphysematous. Lower lobe has a few very small peribronchial firm areas which apparently are lobular consolidations. Bronchi are moderately con- gested and contain considerable frothy, bloody fluid. Pulmonary artery contains a few flat yellow plaques. The bronchial h-mph nodes are slighth' enlarged, black and rather firm. Right lung weighs 590 gms. It does not collapse except on anterior border. On the anterior surface over the upper lobe extending slightly into the middle lobe are very firm fibrous tags enclosing fat. The lung is very anthrocotic on the surface, otherwise has a reddish-blue color. All lobes are firmly adherent b}^ fibrous tissue. On section the lung is air-containing, edematous and appar- ently emphysematous, the surface exuding abundant bloodj^ froth}' fluid. The lower lobe is fii-mer than the upper. It shows moderate congestion but has no definite areas of consolidation. There are no scars in the lung tissue beneath the adhesions described above. The bronchial lymph nodes at the hilus are similar to those of the left lung. Liver. Weighs 1360 gms. The upper surface is red- STUDIES OF SELECTED CASES 245 dish-brown, the lower surface partly stained blue by contact with the intestines. On section it is brown. There is slight evidence of congestion at the center of the lobules and slight fat infiltration at the periphery. The lobulations are not very distinct. The organ is quite flabby and friable. The gall-bladder projects about 3 cm. beyond the border of the liver. It contains light brown mucoid bile with a few yellow flakes. The ducts are patent. Spleeyi weighs 110 gms. Its entire diaphragmatic sur- face is adherent to diaphragm by firm fibrous adhesions. The remainder of the surface is discolored blue where it was in contact with the colon. It is flabby; capsule wrinkled and slightly thickened. On section it is blotchy red-blue in color. Trabeculae appear to be increased. Splenic corpuscles scarcel}^ visible. The tissue is flabby and friable. Suprarenals. Equal in size, small and flat. They con- tain considerable fat in the cortex with a rather broad inner zone and a small amount of white medulla. Kidneys together weigh 230 gms. Right organ is flabby. Capsule strips easily leaving a smooth surface with distinct stellate veins. The kidneys are equal in size. Surface is smooth. Anterior surface is congested. The glomeruli stand out as red spots. The striations are distinct. Medulla appears normal. Pelvis and ureter are normal. Left kidney is more congested than the right. Bladder. It is collapsed but not contracted and con- tains a small amount of bloody urine. The mucosa shows areas of extreme submucous hemorrhage and occasional shallow erosions in the mucosa. Prostate. Grossly normal. Testicles. Left is soft and congested. Has faint brown tinge. Tubules string out. Right is slightly adherent 246 EPIDEMIC ENCEPHALITIS around epididymis to parietal layer of tunica. It is softer and somewhat smaller than the left. The sac of the tunica vaginalis contains a small calcified mass of ma- terial free in the cavity. Pancreas. Is congested but otherwise grossly normal. Gastrointestinal Tract. Stomach shows congestion of the mucosa. The organ contains about 200 cc. of brownish fluid containing many cofTee-ground particles. The duo- denum is normal. The beginning of the jejunum shows extreme congestion. The rest of the small intestine is essentially normal. The mucosa of the appendix shows considerable erosion and contains light yellow material which maj^ be pus, but its wall is not congested. Colon is normal. Organs of Mouth and Neck. The anterior portion of the tongue is covered with patches of thick yellow fur. There is considerable hypertrophj^ of the lymphoid tissue at the base of the tongue. Tonsils are rather large but not inflamed. Pharynx is normal. Oesophagus shows erosion of its mucosa throughout its entire length except upper 7 cm., apparently postmortem digestion from vomited material. Larynx is normal. Trachea is very slightl}^ congested, the congestion increases until it be- comes extreme in the large bronchi. The thyroid is small, rather soft and symmetrical. It appears grossly normal. Head. The calvarium is normal except for a thinning at a point over about the middle of the right parietal lobe beneath which the dura is thin and the pia is thick and contracted and there is some atrophy of the con- volutions. At a corresponding point on the left side is similar congestion except less marked. The pia and arachnoid of the whole brain are slightly thickened and hazy. There is no excess of spinal fluid and the brain is not congested. No gross lesions are found in partial STUDIES OF SELECTED CASES 247 sectioning. Part of the brain is hardened without sec- tioning. The sinuses of the skull and middle ears are normal. Spinal cord appears somewhat smaller in diameter than normal in the thoracic and lumbar regions. There is no gro.ss thickening of the meninges. In the thoracic and lumbar regions it is softer than higher up, particu- larly in the region of the posterior columns. There is no congestion or hemorrhage. No gross lesions of posterior spinal ganglia. Note. The termination occurred as this report was going to press and there was not sufficient time for the microscopic examination of the tissue. SUMMARY The history at onset was of an upper respiratory in- fection with fever and its attendant symptoms. Three days later there developed sudden spontaneous con- tractions in isolated muscles throughout the whole body. The entire voluntary musculature, including that of the tongue and throat, seemed to be involved, with the sole exception of the muscles of the eyes. This continued for three days and then largely disappeared from the head, arms and upper trunk but continued in the limbs. Speech remained difficult and stammering. Soon weak- ness and sensory disturbances in the lower limbs de- veloped; also difficulty in urination, bilateral ptosis and the characteristic stupor of epidemic encephalitis. There was, therefore, clinical evidence of wide-spread lesions involving the brain stem and spinal cord. For a week prior to death the stupor gradually increased. The temperature rose steadily until it reached 104 degrees. The pulse rate continued to advance until the day of termination when it ranged between 120 and 140. CHAPTER XXVIII CONCLUSIONS Epidemic encephalitis is a disease whose virus has a special affinity for the central nervous system. It is prob- able that the disease is similar to anterior poliomyelitis in being a general infection, with its main localization in the neuraxis. The clinical picture varies greatly, but includes both general and localizing signs. The portion of the nervous system most frequently involved is the peri-aqueductal region of the midbrain. No portion of the nervous system seems immune, but the action of the virus on the motor elements is most severe. The more primitive and phylo- genetically older portions of the motor system are more often affected than the later developed pyramidal system. An extensive observation of epidemic encephalitis warrants the classification of the cases into certain more or less well defined clinical groups. Of these the most frequently encountered are the following: 1. The lethargic type 2. The cataleptic type 3. The hemiplegic type 4. The paralysis agitans type 5. The polioencephalitic type 6. The choreiform type 7. The myoclonic type 8. The multiform type. Other less common forms are: 9. The meningitic type 248 STUDIES OF SELECTED CASES 249 10. The acute anterior poliomyelitic type 1 1 . The epilepto-maniacal type 12. The acute psychotic type 13. The sympathetic system type 14. The abortive type. There are a considerable number of cases showing wide- spread involvement of the nervous system without prominent localizing symptoms. Some method of classifi- cation, however, is valuable as an aid in the discussion of the many different forms in which the manifestations of this disease may appear. Concerning the pathogenesis of epidemic encephalitis, as its initial symptoms are frequent h" those of an upper respiratory infection, it is possible that the portal of entr}?- of the virus is by way of the naso-pharyngeal mucous membrane. Whether this is the most frequent or the only situation where the virus gains entrance to the body, or whether the inflammation is due to a sec- ondary invasion of this membrane, is not at all clear. The method of conduction of the infecting agent to the nervous system and the channels by which the infection spreads within the central nervous system, are not known. The similarity of the pathological changes to Heine- Medin's disease and to Borne's disease leads one to sus- pect that it is borne by the lymphatics. The nature of the virus is unknown, though the experimental evidence advanced thus far would point to the probability of its being a filterable virus, possibly related to that of ante- rior poliomyelitis. However, there is very little evidence at present that epidemic encephalitis can be produced in monkeys and certainly not with the ease and reliability with which poliomyelitis is transmitted. Von Wiesner of Vienna was the first to report the results of experimental animal inoculation. His monkey subdurally inoculated 250 EPIDEMIC ENCEPHALITIS with human nervous tissue died in 48 hours with what proved to be a meningo-encephaUtis. A diplostrepto- coccus was isolated from the lesion and was at first sup- posed to be the etiological agent of epidemic encephalitis; but was later regarded as a contamination. Mcintosh reports the experimental production in a monkey of a disease which clinically and pathologically resembled lethargic encephalitis. Loewe, Hirshfeld and Strauss report the production of a meningo-encephalitis by sub- dural inoculation of monkeys and rabbits with the filtrates of naso-pharyngeal washings and naso-pharyngeal mucous membrane from encephalitis patients. The lesions des- cribed have apparentl}^ been more easily produced by fil- trates of naso-pharyngeal membranes and of nasal washings than by inoculations with the infected nerve tissues themselves. The animals employed were mainl}^ rabbits. That extreme caution should be used in judging the value of results obtained by experimental inoculation in rabbits has been noted by many workers, as it has been shown that lesions may be produced in this animal when any foreign material is injected. Other workers have failed to corroborate these findings with similar inoculations. It may be stated without reservation that our knowl- edge of the pathogenesis of epidemic encephalitis leaves much that is obscure. There is at present no evidence that the disease is contagious, and no light has been thrown on the method of transmission. The therapeutic measures are sympto- matic and empyrical. BIBLIOGRAPHY 1. Abrahamson, I. A'. York M. J.. Vol. 109, S94, 1919. 2. Allen, W. C. South. M. 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Ophth., II, 529, 1918. 29. MoTT, F. W. Proc. Roy. Soc. Med., Lond., XII, No. I, Sect, of Med., pp. i — xxiii, Nov. 1918. 30. Neal, J. J. Am. M. Assn., LXXII, 714, 1919. 31. Netter, a. Bull. Acad, de Med., Par., 3. s. Vol. LXXIX, No. 18, p. 337, May 7, 1918. Soc. Med. des Hdpitau.v de Paris, 3 s., Vol. XLII, No. 11-12, p. 307, April 18, 1918. 32. Netter, M. Soc. Med. des Hopitaux de Paris, 3. s.. Vol. XLII, Nos. 15-16, p. 424, Maj^ 3, 1918. 33. PoTHiER, O. L. J. Am. M. Assn., Vol. LXXI, 715, 1919. 34. Robinson, C. A. Indianapolis M. J., XXII, 163, 1919. 35. Rosenow, E. C, and Towne, Edward B. J. Med. Research, Bost., Vol. 37, p. 175, 1917. 36. Sachs, B. N. York M. J., Vol. 109, 894, 1919. 37. Sainton, P. Presse Med., Vol. 26 (2), 486, Sept. 23, 1918. 38. Strauss, I. & Loewe. L. J. Am. M. Assn., LXXIII, 1056, 1919. 39. TiLNEY, F. Poliomj'elitis with Prolonged Somnolence. Neurol. Bull, N. Y., Vol. 1, No. 1, p. 7, Jan., 1918. 40. Tucker, B. /. Am. M. Assn., LXXII, 1448, 1919. 41. Vaidya, S. K. Lancet, Lond., 1918, II, 322. 42. Vaughan, V. C. West. Virg. M. J., XIII, 454-459, 1918-19. 43. Von Wiesner, Wien. kiln. Wchnschr., Vol. XXX, July 26, 1917. 44. Wegefarth, p., and Ayer, J. B. J. A^n. M. Assn., LXXIII, 5-12, 1919. 45. WiisoN, S. A. Kinnier. Lancet, Lond., Vol. II, No. 1, p. 7, July 6, 1918. 46. WooLLEY, P. G. J. Lab. & Clin. M., St. Louis, IV, 456, 1918, 1919. 47. Zuelzer, Influenza. Ziemssen's Handbuch der speciellen Patho- logie und Therapie, 2, 506; part 2, 1874. This volume also includes articles on epidemic encephalitis and on special cases, by Drs. Frederick Tilney, Henry Alsop Riley and Hubert S. Howe, which appeared in the Neurological Bulletin, New York, Vol. II, No. 3, p. 106, March, 1919, and Vol. II, No. 5, p. 190, May, 1919. Paul B. Hoeber, 67-69 East .59th Street, New York. 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