Columbta ©nitJecsfftj) CoUege of S^iipsAcime anb burgeons: Hitirarp LIBRARY CFTiiB ALUMNI ASSaCIATlOli COLLEGE OF PHVSICiAHS A.-^DbUH^ COLUMBIA U N i V ERSI I V NEW YQm Digitized by the Internet Archive in 2010 with funding from Open Knowledge Commons http://www.archive.org/details/cerebrospinalfeOOfost CEREBRO-SPINAL FEVER CAMBRIDGE UNIVERSITY PRESS C. F. CLAY, Manager ttoillioil : FETTER LANE, E.G. CUiniuvgf): loo PRINCES STREET ILoulioil: H. K. LEWIS AND CO., Ltd., 136 GOWER STREET, W.C. EonUoii: WILLIAM WESLEY AND SON, 28 ESSEX STREET, STRAND iacu gorls: G. P. PUTNAM'S SONS SomlaH, Calcutta anB fHatiras: MACMILLAN AND CO., Ltd. STorimto: J. M. DENT AND SONS, Ltd. CTpiiBO: THE MARUZEN-KABUSHIKI-KAISHA All rights reserved CEREBRO-SPINAL FEVER by MICHAEL FOSTER, M.A., M.D. Captain Royal Army Medical Corps, Territorial Force and J. F. GASKELL, M.A., M.D. Captain Royal Army Medical Corps, Territorial Force Cambridge : at the University Press 1916 CambtiSgt ; PRINTED BY JOHN CLAY, M.A. AT THE UNIVERSITY PRESS IN MEMOKIAM M. F. W. H. G Some will allow no Diseases to be new, others think that many old ones are ceased, and that such which are esteemed new, will have but their time. However, the Mercy of God hath scattered the great heap of Diseases, and not loaded any one Country with all: some may be new in one Country which have been old in another. Sir Thomas Bkowue, A Letter to a Friend. PREFACE THIS book has for its aim an attempt to bring together and correlate the clinical and pathological facts which we were enabled to accumulate during the epidemic of 1915. In January of that year, some of the first cases to occur in the Eastern Command were brought to the 1st Eastern General Hospital for treatment, and came imder our care. The earUer cases were admitted in the first instance to different wards and were therefore under the charge of various physicians. Our thanks are due to Major Wright and Captains Curl and Haynes for allowing us every faciUty for stud}dng the cases which had been admitted under their care. To Captain Curl we are especially indebted for much valuable coimsel and help in dealing with these earUer cases. At the end of February the War Office appointed one of us bacterio- logist to deal with the outbreak in the Western part of the Eastern Command. At the same time Colonel Griffiths arranged that a ward should be set apart for the treatment of all cases that arose. We were appointed to have charge of the cases admitted. A laboratory, which had been equipped by the Insurance Act Committee for purposes of research at the 1st Eastern General Hospital, was given for the investigation. In addition to providing the laboratory, the Committee assisted our investigations by appointing Mr H. W. C. Vines to study special problems as they arose. We wish to express our great indebtedness to the Insurance Act Committee for the eqxiip- ment so generously given. To Mr Vines our thanks are specially due as much of his work has been incorporated in the present volume. Major Hele also rendered valuable assistance when the pressure of work was extremely great. In addition to laboratory work, it was the duty of the bacteriologist to visit the place of origin of every case, and investi- gate the hygienic conditions in which it arose. At this visit all contacts were examined to discover carriers. All proved carriers were at once brought into the special Cerebro-Spinal Fever ward, where they were kept under observation until two consecutive throat swabs had proved negative. Every case was therefore fully investigated by us from its commencement to the termination of the illness. We have also had viii Preface the good fortune to see several of our cases some months after their discharge from hospital. The views here set forth are the outcome of cliuical and pathological observations made in the wards, the laboratory, and the post-mortem room of the 1st Eastern General Hospital. Whatever value these conclusions may have, is due to the fact that the clinical and pathological study of each particular case was carried out day by day by the same observers working in conjunction. It has been claimed that the epidemic nature of successive outbreaks differs so essentially that knowledge gained in one visitation is of but slight value in another. Whether this is the case we have no means of knowing ; but we would point out that the cases which came under our care supplied examples of every variety of the disease described in the literature of the subject. The method of treatment by repeated lumbar puncture, which was adopted in the majority of cases, has rendered possible a study of the natural history of the disease and the changes in the cerebro-spinal fluid, unmodified by the operation of any extraneous agent. We desire to express our thanks to Colonel Griffiths for the opportunities of studying the disease which he has afforded us. We are especially indebted to Major Apthorpe Webb for his unfailing assistance in the arrangement and administration of measures which often had to be evolved in face of a sudden emergency. To our brother officers we offer our grateful thanks for their constant help. The plates illustrating this book were drawn by Mr West of the Uiiiversity Press from our own cases and specimens. We are however indebted to Mr Vines for the microscopical drawing shown on Plate XI, fig. 1 . We desire to thank Mr G. A. Harrison, of Caius College, for the photograph illustrating head retraction. Owing to the courtesy of Messrs Longman we have been allowed to introduce three anatomical illustrations from Gray's Anatomy. Through the kind offices of Professor Netter, of Paris, and G. Steinheil, we have obtained permission to reproduce the figure of the lymphatic connections of the sub-arachnoid space and the upper part of the nose, published by M. le Docteur J. -Marc Andre in his Tliese de Paris. To these gentlemen we tender our grateful thanks. M. F. J. F. G. Great Shelfobd January 1, 1916. CONTENTS CHAP. PAGE I. Historical ......... 1 II. Symptoms ......... 13 III. Diagnosis 28 IV. Acute Forms ....;... 41 V. SUB-ACDTE AND ChRONIC CaSES ..... 50 VI. Course and Prognosis . ...... 62 VII. Treatment 72 VIII. Pathology 90 IX. Changes in the Ceeebro-spinal Fluid and the Cultiva- tion OF the Meningococcus from it, from the Blood AND from the Urine . . . . . .108 X. Epidemiology ........ 119 XT. The Bacteriology op the jVIeningococcus and other Gram-negative Diplococci ..... 139 Plates 169 Appendix I ........ . 191 Appendix II ........ . 196 Bibliography and Index of Authors . . . .198 General Index ........ 207 ILLUSTRATIONS PLATES {to follow page 168) I. The Macular Rash II. Fig. 1. The Erythematous Rash Fig. 2. The Petechial Rash III. The Petechial Rash IV. The Purpuric Rash V. Fig. 1. The Communications between the Sub-Arachnoid Space and the Nose Fig. 2. Head Retraction VI. Kernig's Sign VII. Brain of an Acute Fatal Case VIII. Brain of a Suppurative Case IX. Fig. 1. Brain of a Hydrocephalic Case Pig. 2. Brain of an Acute Case shewing Early Hydrocephalus Plate X. Fig. 1. Cord of an Acute Fatal Case Fig. 2. Cord of a> Suppurative Case Fig. 3. Cord of a Hydrocephalic Case Fig. 4. Cord from a Case of Meningitis following Middle Ear Disease Plate XI. Fig. 1. Section of Meninges shewing Meningococci Fig. 2. Film from the Ccrebro-Spinal Fluid in a Fulminating Case Plate Plate Plate Plate Plate Plate Plate Plate Plate CHARTS m TEXT Chart 1. Influence of Lumbar Puncture on Temperature Chart 2. Temperature in Fulminating Case Chart 3. Temperature in Acute Case with Recovery Chart 4. Chronic Fever simulating Malaria Chart 5. Temperature in a Chronic Recrudescent Case . PAGE 16 17 17 17 53 FIGURES IN TEXT Fig. 1. The Cisternae of the Brain . . . ... Fig. 2. Dissection of the Membranes of the Cord . Fig. 3. The Membranes of the Cord in Tran-sverse Section CHAPTER I HISTORICAL Nomenclature — First recorded appearance at Geneva, HirscKs four •periods. First period : Geneva, America, France. Second period : Gascony, Italy, America. Third period : Sweden, Germany, Russia, Greece, Ireland, America. Fourth period : England, Cape Town, Poland, France, Italy. Fifth period : Identity of Posterior Basic Meningitis and Cerebrospinal Fever established ; France, America, Portugal, Silesia, Ireland, Scotland. The English epidemic of 1915. Outbreaks in tropical countries. Geographical distribution. In- fluence of carriers and suitable conditions. Cerebro-spinal fever may be defined as an infection of the meninges caused by a definite organism, the diplococcus meningitidis of Weichsel- baum. The disease occurs in epidemics, which appear at varying intervals, and whose spread appears to follow no definite path. Sporadic cases of this disease are generally present, though in small number, and their identity with the epidemic form has been established by the most rigorous bacteriological proof. This disease has received many names, in whose elaboration practical convenience has been sacrificed to attempts at scientific accuracy. Epidemic cerebro-spinal meningitis accurately defines the main features of the disease, but is cumbersome. Moreover, since every infection of the brain by a pus-forming organism is cerebro-spinal in character, owing to the anatomical re- lations of its membranes, the term cerebro-spinal meningitis appears unnecessarily prolix. Meningococcal meningitis has been suggested by Heiman and Feldstein. This name has the merit of accuracy, but is clumsy in use, and has the further drawback that its general adoption would prevent any attempt to fix upon an adequately descriptive English name. The traditional names of common diseases remain the same through all the chances and changes of pathological fashion. The terms typhus, typhoid and cholera appear to be immutably fixed in medical literature. The name cerebro-spinal fever would seem to F. & G. 1 2 Historical [ch. combine the advantage of pathological accuracy with popular con- venience. It has the further merit that it indicates on the one hand the kinship of this disease with the acute specific fevers, and on the other defines the essential pathological lesion upon which the symptoms depend. If it is desired to draw attention to the epidemic nature of the disease, the term epidemic meningitis is both accurate and descriptive, since, as has been mentioned above, the term cerebro-spinal meningitis is redundant. Various other names have from time to time been given to the disease : of these the one which has attained the greatest measure of popularity is Spotted Fever. This name, which was given to the disease on its first appearance in America, has the drawback that it draws attention to a far from constant symptom. In Italy the disease is called Tifo Apoplettico. In Germany the popular name Epidemische Genickstarre is derived from another marked symptom. Whether the disease is an entirely new one or has always existed, is a matter largely for antiquarian speculation. Some authors think that it can be identified in Hippocrates or Celsus. It would seem improbable that im.til the last century the disease was ever common in these islands, if indeed it ever reached them. Search has therefore revealed no description which can be identified with the disease in the works of Sydenham or Huxham. It has been conjectured that the petechial fevers, references to which fingered in text-books until well into the last century, may have been of this nature, but this is a matter of mere speculation. The first authentic account of an epidemic is that which occurred in Geneva in 180-5. This epidemic presents the singular feature that both the clinical symptoms and morbid lesions were so well described as to establish once and for all the identity of the disease. The out- break occurred in March 1805 ; the first cases appeared in Eaux-Vives, a suburb on the left bank of Lac Leman ; others subsequently occurred at Paquis on the other bank of the lake. The epidemic does not appear to have been particularly widespread, since only thirty-three persons died of the disease. The interest lies in the contemporary records. Vieusseux writes : " The initial symptom was a sudden failure of strength, the expression was anxious, the pulse feeble, sometimes threadlike, in a few cases hard and bounding. There was Adolent headache, in the main frontal. The headache was followed by vomiting of green matter, by stifiness of the spine, and in infants by convulsions. The body shewed livid patches after death, occasionally during life." Matthey has left behind a description of the morbid appearances, to which the pathologist of to-day could have little to add. "The vessels of the meninges," he i] Historical 3 says, " were notably congested. A gelatinous humour covering the brain was markedly tinged with blood. There was fluid in the ventricles. The choroid plexus was of a deep red colour. The base of the brain was covered by yellow puriform matter, with no obvious change in the underlying cerebral tissue. This exudation covered the optic chiasma and extended backwards towards the cerebellum, reaching for the space of an inch down the vertebral canal." From the date of this, its first appearance, the disease was epidemic at various places both in Europe and America for the next ten years. Throughout the last century and up to the present day it has been epidemic for a few consecutive years, and quiescent periods of varying length have then followed. Hirsch has summarized these epidemics in an exhaustive and masterly article in his Treatise on Geographical and Historical Pathology. This author regards the epidemic prevalence of the disease as grouping itself into four periods. The recent epi'demics both in the Old and New World constitute a fifth period. The periods in Hirsch's classification may be chronologically arranged as foUows. The first period from 1805 to 1815. The second period from 1837 to 1850. The third period from 1854 to 1875. The fourth period from 1876 to 1886. The fifth period may be regarded as beginning in 1896 and stretching to the present day. In reviewing the past history of the centres from which outbreaks spread, and the lines of march along which the disease travelled, its propagation appears at first sight to follow no appreciable law. Read in the light of our present knowledge, the part played by the carrier in the propagation of the disease affords a clear explanation of the records of these long past epidemics. Assuming the presence of a few perrnanent carriers, it only requires outside con- ditions which facilitate the spread of the organism, to create a large number of temporary carriers. As Arkwright has remarked, "The number of the carriers constitutes the epidenaic." The persons who fall sick of the disease are thus but the concrete evidences of the wide diffusion of temporary carriers. The apparently enigmatical march of the disease in the old epidemics acquires a fresh interest and meaning, when an attempt is made to trace the path of these long past carriers. In reviewing the first epidemic wave, its place of origin may be taken to be at Geneva in March 1805. Its next appearance was in the New World in March 1806 at Medfield in the Commonwealth of Massachusetts. As to whether any emigration from Switzerland took place there is no evidence, but there has always been interchange between Geneva and North America. From Medfield the disease spread through the 1—2 4 Historical [ch. New England States of Connecticut, Vermont and Maine, where it recurred in isolated epidemics until 1816. The disease spread to Canada in 1807, to Virginia, Kentucky and Ohio in 1808, appearing in the State of New York and in Pennsylvania in 1809. This American epidemic was remarkable for the coining of the popular name of spotted fever, by which name it is described in a book entitled Treatise on a Malignant Epideviic called Siiotted Fever, written by North in 1811. In Europe the disease appeared amongst the Spanish prisoners at Brian§on in 1807. In 1811 it occurred at Dantzig, then in French occu- pation. An outbreak occurred in the garrison at Grenoble in February, March and April 1814. The garrison of Paris was attacked during the same months. In the spring of 1815 it occurred at Metz and Pont a Mousson. In the same months an epidemic occurred in Albenga and some of the surrounding villages. This epidemic was of importance, since it was described by Sassi in 1815 under the title Saggio sulla spinite epidemica che ha regnato in Albenga, and was also described by Mela and Airaldi. It is a matter for surprise that a remote city on the sea-board of the Ligurian Alps should be the seat of an epidemic confined apparently to the valley in which it stands. When viewed from the point of view of the possible importation by carriers, the problem appears simpler. From Albenga the road leads up to the main pass into Piedmont, which is the only practicable one along a stretch of momitain ranges 70 miles in length. At the mouth of the river, on which Albenga stands, is the safest roadstead between Nice and Genoa, where to-day brigantine and felucca can be seen sheltering from any sudden gale. The sea-borne traffic was in those days considerable, the coast road having been a mule path less than twenty years before the epidemic. Infection could thus reach Albenga both by land and sea. Once established the infection might well be limited, as every one of the valleys bordering the shores of the gulf of Genoa is a country apart from its neighbours, each of them to this day presenting marked individual differences in dialect. From the year 1815, with the exception of two small and purely local outbreaks in America, the disease remained quiescent until the second period, which Hirsch dates from 1837 to 1850. The first appearance of the malady was in the Landes and the valley of the Adour in 1836. Ferron, who has made an exhaustive study of the beginnings of this epidemic with most interesting results, regards the place of origin as Sengresse in the Landes. It was brought thither by a Spanish family who had left their native country on account of an epidemic, the nature of which is not recorded. The first person attacked was a maid-servant, thirty i] Historical 5 years of age, who died ou the 15th of February 1832. The Carlist war then raging in Spain had led to the concentration of a large body of troops in this district. Such a concentration of troops, for the most part in billets, involves a considerable amount of overcrowding. Further, their mere presence and their changes of station involve a relatively larger shifting population than is met with in ordinary civil life. The conditions were therefore similar to those which obtained in England in the winter 1914-15. The introduction of carriers in such circum- stances enabled the disease to estabUsh itself. From the Landes the contagion spread to the garrisons of Bayonne and Dax. Amongst the troops quartered in the Landes at the time of the first outbreak were the 18th Light Infantry, who were early attacked. They changed quarters to Bordeaux, where the disease continued. From Bordeaux the regiment marched to Rochefort, where fresh cases occurred in January and February 1838. In the latter part of this year the 18th moved from Rochefort to Versailles. At the latter station six men living in the same room were attacked in February 1839. The disease then spread through the regiment, and finally attacked the whole garrison. The further wanderings of this regiment next brought it to Chartres, where the disease again broke out. From Chartres the 18th moved successively to Metz, Nancy and Strasbourg, carrying with it the infection, which soon manifested itself in the garrison of each station. What Netter aptly terms the Odyssey of the 18th regiment presents a remarkable record of the human agencies which conveyed the disease from the Pyrenees to the Rhine. At the same time that the disease broke out in the Landes, it also appeared at Narbonne and Foix. In the following year it spread to Toulouse, Nimes and Toiilon. In the winter of 1839 it appeared at Avignon, and in the following winter it spread from the military to the civil population. In 1840 it appeared in Algiers, a considerable number of cases occurring amongst the garrison. Marseilles was attacked in the winter of 1841-2, and an outbreak of a malignant character occurred at Aigues Mortes. The latter town, with its houses crowded together within the circuit of its high surrounding walls, forms possibly one of the worst ventilated towns in the world, so that the gravity of the epidemic can hardly be a matter of surprise. At the same time as the disease prevailed in France, it appeared also in Italy. The first outbreak occurred at Ancona in 1839; as Netter points out, French troops consisting of regiments of infantry and artillery had been maintained in this city since 1832. These regiments were constantly receiving recruits from France, whence it e Historical [en. may be inferred that the disease was brought by carriers. The brunt of the epidemic fell upon Naples and Calabria. The disease was present in Sicily in 1844. Corfu had already been visited by the disease in 1840, the infection having apparently been brought from the port of Sinigaglia near Ancona. In 1844 an epidemic occurred at Gibraltar, where the usual course of events was reversed, the civil population being the ones to suffer, while the garrison went largely unscathed. The strict regulations separating the military and civil population, which have always been in force in this station, probably account for the escape of the soldiers. In the spring of 1845 epidemic meningitis appeared in Denmark, Copenhagen in particular suffering. In the following winter it reappeared, Iceland also being afEected. The United Kingdom had hitherto escaped the visitation of the disease, with the exception of two small epidemics which are cited by Ormerod. The first occurred in a Dartmoor village in 1807, but the recorded description by Gervis leaves the nature of the disease extremely doubtful. The second occurred at Sunderland in 1830 ; its description, however, was not published by Scott until thirty-five years later; so that the nature of the outbreak is without adequate confirmation. In the winter of 1845-6 the disease first appeared in an epidemic form in the workhouses at Dublin, Bray and Belfast. A few cases occurred also in Liverpool, and a small epidemic, as to whose nature some doubt exists, is recorded by Brown at Eochester in 1850. One case occurred at Haslar Hospital. In America a second visitation of epidemic meningitis occurred in 1841. The disease first appeared in Tennessee and Alabama. In 1845 and the following years outbreaks occurred in Illinois, Arkansas, Missouri and New Orleans. In 1848 it spread east- wards to Pennsylvania, and appeared in Massachusetts, but was limited to two small townships. A somewhat striking feature in this second visitation is the immunity enjoyed by the New England states, which suffered so severely in the first epidemic. It may be remarked, however, that the shifting character of the population in the States of the Middle West at this date may have had some influence on the propagation of the epidemic. Hirsch's third period begins with the year 1854, when the disease appeared for the first time in Sweden. The method of spread of this epidemic differed in a marked manner from that observed in previous ones. In place of widely scattered isolated centres, the disease advanced in a systematic manner from the south-west in a northerly direction. With each succeeding annual recrudescence, fresh outbreaks occurred i] Historical 7 near the northern limit of the previous manifestation. The localities stricken by the epidemic of the year before escaped, while with each recurrence of the disease fresh districts were invaded. The disease also spread to a limited extent to Norway. In Germany a few small and unimportant epidemics had occurred in the earlier periods, in 1827 in Rhenish Prussia and in 1843 and 1851 at Leipzig. In the year 1863 the first serious outbreak took place in Silesia. In the following year East and West Prussia, Posen and Brandenburg were attacked. A year later Hanover and Brunswick were in turn invaded. In Southern Germany the epidemic first broke out at Nuremberg, and appeared coincidently at other points until the greater part of Bavaria was attacked. Austria-Hungary seems to have been largely spared, with the exception of an outbreak in an orphanage at Vienna and small epidemics at Pola and Trieste. In Russia there were minor epidemics in Moscow and Warsaw, and a general epidemic in the Crimea. In Greece the disease first appeared in 1863-4 and was generally epidemic in 1868-9. Ireland was visited for the second time in 1866-7, an epidemic occurring in Dublin which afEected both the troops and the civil population. The severity of this epidemic may be gauged by the frequency of haemorrhagic rashes, and the coincident high mortaUty. The disease also appeared at Bardney in Lincolnshire in 1867. In connection with this apparently isolated outbreak, it must be remembered that farmers near the recently reclaimed fenland were in the habit of employing gangs of reapers from Ireland, and that this may have been the method by which the infection was imported. In this epidemic wave, which was both more concentrated in point of time and more universal in distribution than any of the preceding outbreaks, America did not escape. The main site of the epidemic was not, as on its first appearance, in the New England States, nor, as in the second, in those of what is now styled the Middle West, but mainly in the Southern States. Two outbreaks anticipated the European epidemic, one in North Carolina, the other in the State of New York. The Civil War brought in its train all the attendant circumstances necessary to engender an epidemic — overcrowding of troops and, with their move- ments, a rapid shifting of the population. The disease broke out in the army of the Potomac during the winter of 1861-2, and was followed by a severe epidemic which ultimately involved the greater part of Pennsylvania; Indiana and Virginia were next attacked in 1866-7, and Kentucky also suffered. Finally, in 1873 the disease appeared in Massachusetts, and at Boston in 1874. The American epidemic began 8 Historical [ch. earlier and lingered longer than the corresponding wave in Europe, which may be regarded as ending in 1869. After this date the appear- ance of the disease was for many years limited to slight and widely separated outbreaks. Hirsch's fourth period begins in 1876, in which year there was a minor epidemic at Birmingham, nineteen cases being treated at the Queen's Hospital and several others occurring outside. In 1877 a small but relatively fatal epidemic occurred at Cape Town. In the succeeding years epidemics occurred in Silesia, Poland, Galicia and Hungary. There were also small epidemics in France, Sicily and Greece in the early eighties. In 1885-6 there were slight epidemics of the disease in Paris, Milan and Turin. The appearance of the disease in Vienna at this date has an historical interest in that it led to the isolation of the meningococcus. In 1885 the disease appeared in the Fijian Islands. In 1884 an epidemic occurred near Kilmarnock: of seven persons attacked, five died. In 1887 a series of cases in infants occurred in the north of London. These cases, which occurred in children, were distinguished cUnically by marked retractions of the head, and pathologically by the presence of purulent meningitis. They were treated in University College Hospital, and during the same period two cases of purulent meningitis in adults were admitted with marked head retraction. Several other such cases occurred in the north of London. The cases at University College Hospital were observed by one of us, and were regarded by the late Sir William Gowers as probable examples of cerebro-spinal meningitis. Kegarded in the light of subsequent experience, no doubt would occur as to the true nature of these cases. The outbreak in the eighties would appear to have been of a very minor character, and was foUowed by a period during which the disease remained largely quiescent. Before the appearance of the next epidemic wave, which Osier regards as the fifth, the whole aspect of the disease as regards diagnosis had been entirely changed, by the isolation of the causative organism on the one hand, and the demonstration of the facility and safety of the operation of lumbar puncture on the other. From this time statistics, whether of the frequency of occurrence of the disease, or of its distribu- tion, or of the results of treatment, acquire a new and more accurate significance. Another discovery was made in 1898, which has also proved to be of great importance from the epidemiological point of view. The identification of the meningococcus as the cause of posterior basic meningitis by Still put an entirely new aspect on the relation of one epidemic to another. Posterior basic meningitis was first i] Historical 9 differentiated clinically as a form distinct from other varieties of meningitis by Gee and Barlow in 1878, but its relationship to epidemic meningitis was not then realized. Since its identification, posterior basic meningitis has been recognized every year in most of the large towns of England, and is to be looked upon as a sporadic form of epidemic meningitis which is always present. It is not necessary, therefore, to attempt to trace a direct spread for any particidar epidemic, since the matter is more a question of the occurrence of the appropriate conditions than of the introduction of an extraneous infective agent. In the year 1898 there was a recrudescence of cerebro-spinal fever in France. America again suffered a visitation in this year, which has acquired significance from the researches then conducted by Councilman, Mallory and Wright. In 1901-3 a severe epidemic occurred in Portugal in which there were no less than 3000 cases, a heavy toll in proportion to the population. This epidemic has further interest in that lumbar puncture as a thera- peutic method was then first employed by Fran9a. In 1904-5 a severe epidemic broke out in New York and the New England States. In New York alone in 1905 the cases amoimted to 2755. This epidemic lasted with diminishing iatensity through 1906 and 1907 ; its close is remarkable in that serum treatment was then first introduced by Flexner. Silesia was once more attacked, 3317 cases occurring there during the year 1907. In the year 1911 an outbreak occurred in the South-Western States of America. The succeeding year 1912 witnessed an extensive epidemic in the State of Texas, the disease originating in the larger towns, notably Dallas, and thence spreading to the country districts. In this epidemic Sophian had great opportunities of studying the clinical and bacteriological features of the disease and utilized them admirably. In the four preceding periods of Hirsch's classification the United Kingdom had enjoyed a marked relative immunity. The Irish epidemics, and a comparatively unimportant one at Birmingham in the seventies, constitute the only outbreaks to which the term epidemic can fitly be applied. It was not until the earlier years of this century that extensive epidemics of the disease have occurred within these islands. In 1902 a small epidemic of forty or fifty cases occurred in Dublin, but no extension followed. In the end of the year 1906 cases began to appear in Belfast, a month later five members of one family were attacked within thirty hours of each other. The epidemic how- ever did not begin in earnest until the end of February 1907. By the end of August, Eobb had treated 275 cases in the Belfast hospitals. 10 Historical [ch. During the next year ninety cases passed through the Belfast fever hospitals. Up to the end of 1914 only twenty-seven additional cases had come under Robb's care. From this it would appear that the epidemic was at its maximum in the first year, and had practically disappeared at the end of eighteen months. The total epidemic in 1907-8 consisted of 725 cases, about half of which therefore passed through Robb's hands. Almost simultaneously with the outbreak in Belfast cases began to appear in Glasgow. Currie and MacGregor state that the first cases were admitted into the Glasgow Fever Hospital in May 1906. For the rest of the year cases averaged about seven per month, but early in 1907 the disease became epidemic, and in April of that year forty-two cases were admitted. In the two years 1906-7 and 1907-8, 330 cases were admitted into the Belvedere Fever Hospital. The total number of cases in Glasgow was 1238 ; according to Chalmers more than a thousand of these occurred in the period 1906-7. This epidemic thus presents a marked similarity to that in Belfast as regards the abrupt decline noticeable in the second year. Edinburgh was also attacked during the same period but to a lesserdegree, 138 cases occurring. During and after this main outbreak a few small and scattered epidemics have occurred up and down the country. The continuance of the disease led the authorities to make it notifiable in 1912. In the years 1912, 1913, 1914 about 300 cases were notified annually. The early months of the year 1915 witnessed an epidemic, the first of its kind really to affect England as a whole ; previous epidemics had been confined to the industrial towns of Scotland and Ireland. But conditions had entirely changed, the whole face of the country was covered by soldiers in training, by force of circumstances overcrowded in billets and exposed to changes of weather without any adequate means of drying themselves. Conditions such as these tended to a lowering of individual resistance, the changes being greater than would ever occur in any community of men during peace time. Owing to the system of billeting, soldiers and civilians were brought into close contact, consequently the disease was almost equally distributed amongst the military and civil population. The main distribution was in places where troops were most closely concentrated, namely on Salisbury Plain, at Aldershot, in the London area and the Eastern Counties of England. The statistics of the epidemic of 1914-15 are still in a condition too incomplete for any final study. Col. Reece has however published full statistics of the cases which occurred amongst the troops. In the years 1906-7-8 extensive outbreaks occurred in West Africa i] Historical 11 and the Northern Territories of the Gold Coast; that of 1907 is stated to have caused no less than 10,000 deaths. East Africa was visited by an epidemic in 1913, which is of interest as treatment by soamin was attempted for the first time to any extent. An outbreak amounting to some 200 cases occurred in the Transvaal in 1907. Col. Wilkinson states that outbreaks of the disease occur from time to time in India, notably in jails and famine rehef camps. Here again the conditions hitherto noted in connection with the spread of the disease, over- crowding of a shifting population, are a marked feature. The foregoing facts prove that the disease is more widespread in tropical countries than is generally recognized. A survey of its geographical distribution shews that epidemics have occurred from the Equator to within the Arctic circle. Nor has the disease been confined to one hemisphere alone, the southern hemisphere has been afEected as well as the northern. Chmate fer se can thus have but sUght influence on the occurrence of an outbreak, an explanation must rather be sought in the hygienic conditions of any given community. Regarded from the standpoint of our present knowledge of the disease, a survey of the epidemics of the past reveals several striking characteristics. The importance of the carrier in spreading the disease is illustrated again and again in different epidemics. The most remark- able illustration is the almost fantastic story of the wanderings of the 18th Light Infantry, who during the course of a few years carried the disease from one end of France to the other. The outbreak in Southern Italy, which began in 1839, was almost certainly due to the presence of a French garrison at Ancona, the starting-place of the outbreak. Recruits were constantly arriving in this garrison from France, where the disease had been prevalent for some years. The frequency with which seaports have been either the starting-place of an epidemic or its exclusive seat, indicates again the part played by carriers from overseas in infecting the population. The infection of the island of Corfu from the port of Sinigaglia is an instance in point, and it may be surmised that the Albenga epidemic had a similar origin. Outbreaks of any magnitude in the British Isles previous to 1914 had always occurred in seaports. It is probable thut the importation of a carrier does not lead to an immediate epidemic, as is instanced by the outbreak in the Landes, when an interval of three to four years elapsed between the first case and a general prevalence of the disease. The frequent occurrence of outbreaks in camps, garrisons and seaports is also partially accounted for by the inevitable occurrence of periods 12 Historical [ch. i of temporary overcrowding connected with the life of such places. By contrast it may be noted that the occurrence of a case on board ship is a very rare event. In the epidemic of 1914-15, in the Royal Navy out of a total of 170 cases only two occurred on board ship. It may be inferred that, though the number of persons crowded into a ship is considerable, the free ventilation renders a carrier innocuous. A further condition has been present in many outbreaks. Either owing to war or to other conditions, the population in the site of the outbreak has been constantly shifting. A great number of persons are thus brought into contact with each other, and, as the influx is usually greater than the housing accommodation can deal with, this contact is often extremely intimate. In consequence a greater number of persons are exposed to carriers under conditions favourable to the spread of the disease. CHAPTER II SYMPTOMS Onset, headache, vomiting, delirium, stupor, coma, temperature, pulse, respiration, rashes, herpes. Aspect, sphincters, head retraction, other rigidities, Kernig''s sign, reflexes, ocular palsies, other palsies, nervous sequelae. Affections of the eye, optic neuritis, affections of the ear, deafness. Initial Coryza, the throat, the lungs, bronchitis, pneumonia, affections of the heart, affections of the kidneys. In any study of the symptoms of cerebro-spinal fever the subject has to be approached from two points of view; the coiixse of an acute specific fever on the one hand, and the gradual development of nervous phenomena, due to changes in the organ on which the brunt of the infection falls, on the other. As a general rule, cerebral or spinal symptoms develop some time after the patient has been stricken down by an ob^aously acute illness. The onset of cerebro-spinal fever is as a rule sudden. Like pneumonia and typhus, the disease is frequently ushered in by a rigor. In the greater number of our cases, the patient was apparently in his ordinary health when he suddenly began to shiver, this varying from a mere sensation of chilhness to a prolonged period of violent shaking. In other cases again the onset is more insidious, a short period of general malaise with some headache being succeeded by an increase of headache, until the supervention of vomiting finally calls attention to the probable nature of the malady. A striking feature in many cases is complete loss of appetite, amounting even to absolute revulsion against any kind of food. The onset in the fulminating or foudroyant type is very sudden, coma may occur either during sleep, or an hour or two after onset. One of our cases, which terminated fatally, was found unconscious in the morning, having been in ordinary health the night before. Another case was found dead in bed. That an onset of such startling suddenness, though usually asso- ciated with a fatal result is not necessarily so, the following case will shew. An officer's servant, who had been at his work the night before, was found unconscious in bed at 2 a.m., and removed to the base 14 Symptoms [CH. hospital at Cambridge. On admission he was unable to swallow, there was retention of urine and nystagmus ; lumbar puncture was performed and repeated daily for three days. At the end of 24 hours he was able to swallow, and was entirely free from all symptoms on the sixth day. This patient remembered nothing from going to bed before the attack imtil the fifth day. From this it would appear that the onset may be so sudden as to overwhelm the sensorium without any warning symptom, and yet be followed by a rapid recovery. The immediate and salutary effect of lumbar puncture would suggest the view that the symptoms were largely due to sudden rise of intracranial pressure. In another case the patient was suddenly seized with dizziness while riding on a bicycle; he fell from his machine and with difficulty made his way for a mile to his home; his temperature was then found to be 104. Delirium rapidly set in, but after a tedious illness eventually he completely recovered. The disease may begin during convalescence from influenza, measles or pharyngitis, and thus closely simulate a relapse. The preliminary rigor of the onset is either accompanied or rapidly followed by headache; this varies in its initial severity and the rapidity with which it becomes more intense. The headache generally affects the whole head, occasionally it is more marked in the occipital region, occasionally in the frontal. In none of otir cases was it ever imilateral. When once the headache has begun, it steadily increases in intensity, intermissions are uncommon and the pain is rarely soothed by drugs. When persisting, the pain may be of the most agonizing description, the patient's fortitude completely breaking down, till he fills the ward with his cries and moans. The headache continues for days, even when a state of delirium is present, but may at any time be replaced by coma. Accompanying the headache there is a varying degree of photophobia; but this is not nearly so marked an early symptom as in tubercular menin- gitis. With the onset of headache, vomiting occurs in practically all cases within a comparatively short space of time. The period of its first appearance varies from about three hours to three days ; it may be entirely absent in the fulminating type. In one fatal case there was no vomiting, but severe diarrhoea. The urgency of vomiting varies markedly in the different cases: in some it is limited to one or two attacks, in others it is continuous for 24 hours. On the whole, it may be said that, although always present to some extent, it is not so continuous and distressing a symptom as in other cerebral affections. A variable time after headache and vomiting, delirium makes its appearance. This symptom is a fairly common one in adult cases; n] Symptoms 15 out of thirty-six consecutive cases delirium occurred in twenty; ten passed gradually into a state of coma without the supervention of delirium, and in six cases delirium was not noted at all. The date of onset of the dehrium varies within considerable limits, the earhest being three hours from first feeling ill, and the latest on the sixth day. In one case delirium, which was absent during the primary attack, made its appearance during a recrudescence. In the majority of cases, this symptom was first observed on the second or third day. The character of the delirium varies from mere muttering to absolutely maniacal excitement, the dehrium ferox of older writers. Many of the patients are very noisy, one man in his waking moments shouted so loud as to be heard 200 yards from the hospital. Another case was regarded at first as dehrium tremens. A feature of the delirium is constant reference to the extreme intensity of the headache. Headache does not cease when delirium begins. With the dehrium there is associated a considerable degree of restlessness, the patient constantly trying to get out of bed ; some cases may be so violent as to require men to hold them. Associated with the general restlessness in less active forms of delirium, there is sometimes seen the symptom called by the old physicians floccillation or carphology : this consists in constant movement of the hands over the bed-clothes or in front of the face, the purpose apparently being to draw some object towards them. It does not occur with any marked frequency, and, although only present in grave cases, does not appear to have the sinister significance which its presence betokens in typhus. This carphology must be distinguished from the fighting movements of the hands such as are seen in cases of extreme dyspnoea. Subsultus tendinum occurs, but this again is not of such grave significance as in other diseases. In a considerable proportion of cases delirium is succeeded by stupor, which after an interval of varying length passes into coma. In other cases again, coma may supervene upon the stage of headache and vomiting without the preliminary stage of delirium. The fulminating case may pass into a state of coma without any warning symptoms. Coma was present at some stage or another in twenty out of thirty-sLs of our cases. The degree of stupor or coma varies markedly, in the more severe types the condition is profound. The patient lies like a log, unable to swallow, mucus rattUng in his throat : desperate as such cases appear, some of them make a rapid recovery, if the pressure is reheved early enough. In other cases there is a period of semi-coma, from which the patient can be roused to take nourishment or even to answer questions. 16 Symptoms [CH. Possibly in no disease is the temperature less a criterion of the severity of the case than in cerebro-spinal fever. As a rule, in mild or sub-acute cases, the temperature rises at once to 101-103 and remains near this level for several days, with considerable daily remissions. As lumbar puncture exercises a considerable influence on the course of the temperature, it is difficult to estimate the distinctive temperature curve. Following the initial rise, the temperature follows no regular course; remissions with an apyrexial period followed by a subsequent further rise of temperature commonly occur. Lumbar puncture usually produces a definite drop, followed by a rise after a varying interval. Chart 1 shews the temperature curve in an acute case in which lumbar puncture was repeatedly performed. The height of the temperature forms no criterion of the severity of the disease, some of the most Chart 1 ^ ■'„ ,aX,o -F m- eio -n tn- 77o « J.,0 ?fl .... ?p 10? 2n !0Z eiD ,., i ^ %: "1 k > *; R } ., i s ■S ^ »; •j^ r' fe k fe 1 :| i ,^ : ,.. ;| ^- 1 ; ^: i ■»■ -1 ^: ^ ^ 1 ti .,. i| 3- i ■•>! ^^ 1^ •■■ 1 A l\ f -J «,■ ^! i h / V \ \ 1 ^ f* \ ..• i ^ 1 \ y f / . , /: ,.. \ 1 V \ A \ \ .,■ 1 / V -rf ..„^ / ae \eo m si °fiff m 64- <% 7Z J'r. lOQ /2 /2 n '% Kartniluits / 20 ■2+ f% M n. \ ^0 20 20 f?. 20 m «2 22, r.. ^. fl 2Q 22- l?0 '20 201 20L24- ^ rapidly fatal cases shewing but a very slight rise. Charts 2 and 3 shew the temperature in two cases, one of which was fatal within 30 hours, the other, already referred to, was found comatose in bed but re- covered. The cases which recover often drag on for a long time with apyrexial periods followed by occasional recrudescence of fever which is usually attended by a return of symptoms. The fever in some cases presents a strange resemblance to a tertian ague, in others to a quotidian. Chart 4 is an example of this. Just before death the temperature may rise suddenly to 105 or more, more usually the previous level is maintained till death. Fulminating cases differ in the respect that the collapse before death is accompanied by a fall of temperature to below 97. In the earlier stages the pulse is somewhat quickened, but as a rule n] Symptoms 17 not to the extent wliicli would be expected from the temperature. The frequency varies from day to day, not necessarily in accordance with the fluctuations in temperature. The occurrence of a pulse of 60 to 80 accompanying a temperature of 101-103 is not imcommon in the early stages of the disease, and is of considerable diagnostic import- ance. Nine out of twenty-three cases which came under our care shortly Chart 2 Chart 3 - ?■» »■? fi-m ?■(! /f7-? ... ?.« m-p ?-s m-7 e-i(i ?-B 10-7 6-10 2-6 10-2 e-g, m I0-2 e» lor ; ,.,■ ! : ,«• -as- .«• \ IM ...■ i 103- • .0.- : .02 ,.!■ : ; : .o,- ■ ,=,• : .CO- ■ .«=• \ r f. ..• R „■ \ / ^ I \ ^ f\ / „. ( \ - i \ m^ „. T r J ' * \ / «■ <-„--./. -m /■ ^ •*7 ■^ 9^ -1JI) / [ BO \ 7J 76 76 52 S5 52 60 ^52 18 IS St- ,13 ' 1 5i. 18: J ^sr / SS"~ / !r ./. / yio ■ io ,' \^0 IB 'B 78. IS. IS IB 18 /?, li 20 20 16 18 '"1 Chart i ~ ~ 6.,n ,n-- 6.m ,■6 w.. 6.« p-fi „., S-K. ?B in-? K-IO IS lo-r 6-10 26 lO-i 610 2-6 ro-J «.« i-6 ,.. if ■ : .„ m : 10. ■ ■ ... r ►A ,„. N > f ^ f ^ N ,», \ ^ f 1 f. / \ _j/ 1 „ \ / \ 1 ^ 1 1 '\ ■ r / I* , _i 1 __ & -^ _}_ A _^ \ l»* /_ t- -y? ~ j] ~ ~ ~ P z M ^ ^ „ _ _ K i r^^.,^ ai-' w "sr n 's2 \os w Bfl eo 88 HS IIS ^S8 9$ '98 w 20 W 61 V 6S 68 m B¥, 76 1 1, 2f La 22 M 'Srsr 22 18 20 v^ 20 22 r^o JO 1. 20 20 22 22 % \ 20 l£ M % IM 1i ^ after onset, shewed a marked slowness of the pulse with high temperature. At a later period the pulse changed from its previous slow full character, becoming much more rapid. In sub-acute cases the pulse is some- times irregular at quite an early stage. In the fulminating and acute varieties the pulse is very quick and running from the onset. When F. & a. 2 18 Syinptoms [CH. hydrocephalus supervenes, the pulse may suddenly change from its former character and become extremely rapid and feeble. - The respirations in the majority of cases are slightly but not markedly quickened; in some however the respirations are very rapid, forty to fifty in the minute without any pulmonary compUcation. They may vary from time to time, and may drop at once to normal on the administration of an anaesthetic before lunibar puncture has been performed, which proves the central origin of the condition. With this rapid respiration there may be almost rhythmical variation in frequency and depth; and not uncommonly sighing respiration is noticeable. This type of respiratory irregularity is called Biot's respiration, or cerebral breathing. Cheyne-Stokes breathing is present as a terminal symptom both in the acute cases and, notably, in cases which are in a condition of hydro- cephalus. In the fulminating cases urgent dyspnoea is a marked symptom. The breathing is very rapid, 60 or more to the minute, while the patient beats the air with his hands. Death may occur from sudden respiratory failure, the heart continuing to beat for some time after respiration has stopped. This method of death is more frequently met with in this disease than in others, and is due to pressure on the fourth ventricle. The pulse respiration ratio is of some diagnostic importance, it never exhibits the regular increased ratio seen in pneu- monia. The aspect of the patient in the early stage is characteristic, the face is usually flushed and the expression one of suffering, which later, as stupor approaches, gives place to a heavy dull look somewhat resembhng typhus. The patient usually lies curled up in bed during the earlj^ stage, but, as retraction becomes marked, assumes the unmistakable attitude which this symptom produces. Sometimes the patient rests on his elbows face downwards, supporting the head with the hands. Four distinct varieties of rash may be observed in the course of the disease. (1) A macular rash ^^ath fairlj^ uniform distribution ; (2) A fugitive erythema appearing in different parts of the body; (3) A petechial rash; (4) Vibices or large purpuric spots. The macular rash (Plate I) follows a fairly definite course both in aspect, distribution and date of eruption. The individual maculae vary in size from a millet seed to a No. 1 shot, and they do not disappear on pressure. The variations in colour may represent any hue from that of a scarlet geranium to a ripe grape. The distribution is fairly uniform, ii] Symptoms 19 the rash being first discernible on the abdomen ; it subsequently appears on the thighs, the extensor surfaces of the forearms and legs, and finally on the backs of the hands and dorsum of the foot. The maculae as they fade leave a slate-blue staining. This rash occurred in ten out of thirty- nine of our cases, and appeared in the majority of instances on the fourth day. In one case it was reported to have appeared on the second day, and in a very severe case it only appeared on the eighth day, when convalescence had set in, but had been preceded by patches of fugitive erythema. This rash does not come out in successive crops, it begins to fade rapidly, and at the end of four days nothing but staining is to be observed. The eruption may be regarded as the true specific rash of the fever, though it is probably the least regular of all the exanthemata. The erythematous rash (Plate II, fig. 1) is analogous to the transient erythema which may precede the eruption in small-pox or typhus. The erythema may appear on any part of the body and at almost any stage of the disease. The rash is uniform or mottled, and varies in colour from pink to bluish red. The duration is usually short, lasting only a few hours. In one instance sUght staining was left behind. This rash occurred in six of our cases, two of which were fatal. The latest date on which it made its appearance was the thirteenth day. The third form of skin eruption is the petechial rash (Plates II, fig. 2 and III). This consists of small papules, varying in size from a pin's head to a peppercorn, of a purple red, or bright copper colour. In distribution it reveals its traumatic character, being always found at points where pressure is most unavoidable. Consequently it makes its appearance on the knees, elbows, malleoli and the points of the shoulders. Where the patient has scratched himself or been bruised, patches of petechiae with surrounding erythematous redness will be found. The nature of the eruption is evidence of profoimd toxaemia, it occiirred in six cases out of thirty-eight and was in each instance accompanied by a fatal result. It appeared from the first to the third day. The purpuric rash (Plate IV) is merely an exaggerated form of the last-mentioned. It occurs in large spots, "vibices" of the older writers, varying in size from that of a bean to a pea's pod, and of a dark purple colour. The distribution is irregular, in the only case which came imder our observation it occurred on the thighs, knees, ankles, dorsum of foot and was well-marked on the face. This- latter is an unusual distribution in the purpuric rashes associated with other diseases. This 2—2 20 Symptoms [CH. eruption, whicli is common to all profound infections and is identical with the mediaeval plague spot, only occurs in fulminating and fatal cases. In a considerable proportion of cases herpes appears ; this symptom occurred in fourteen out of thirty-nine of our cases. The eruption appears from the third to the sixth day, the fourth day being the most usual. In one fatal case the vesicles involved the entire circumoral circle, invading the mucous membrane to a considerable degree. Both facial and labial herpes co-existed in one case, while in another the eruption involved the ear as well as the labial and submental areas. Herpes is said to occur on other parts of the body, but this did not come under our observation. Netter, however, figures an eruption occurring along the course of the fifth lumbar nerve. The above train of symptoms are those manifested by an acute febrile affection. The signs connected essentially with the nervous system may now be considered. The sphincters are affected in a large proportion of cases. In the pubhshed works on the subject no great- stress has been laid on this symptom, and yet it is of considerable importance from the point of view of early diagnosis. Out of thirty-nine of our cases, the sphincters were affected at one time or another in twenty-six. Retention of urine occurs at quite an early stage in a con- siderable number of cases, in one this was the sole cause of the man reporting sick. In twenty cases a catheter had to be passed on ad- mission, fourteen of these cases were dehrious, but the other six were quite conscious, and in no sense acutely ill. In such cases the presence of retention is a valuable aid to early diagnosis. In one case there was difficulty in micturition, but no retention. Two other cases were admitted with incontinence. In the milder cases the retention passed off after the first or second lumbar puncture ; in the more severe cases which recovered, it disappeared after two or three days. Other cases developed incontinence both of urine and faeces at a later date, notably those which became hydrocephalic. Inability to swallow was present in six cases on admission ; they were at the same time profoundly unconscious. Of these, three died and three recovered. One fatal case became unable to swallow shortly after admission. In all our other cases, the power of swallowing was never entirely lost, though great difiiculty was met with in getting them to take food by the mouth. In association with the headache at the onset of the disease, there is often marked pain in the back and thighs with considerable muscular n] Symptoms 21 rigidity. Sooner or later pain and rigidity in the muscles of the neck makes its appearance, giving rise to the characteristic sign of head retraction. This sign, which is of great diagnostic importance, varies markedly in degree and in the date of its appearance. In a suspected case the muscles of the neck should be thoroughly examined; often nothing but some shght tenderness can be made out, though with further manipulation a shght amount of stiffness can be ehcited. This stiffness differs from that accompanying rheumatic affections, in that the latter is lessened by manipulation, whereas the former is increased. The patient is imable to nod the head, and lies on his side rather than on his back, so as to relax the muscles. The primary pain and stiffness go on increasing at a variable rate, until the increasing spasm of the muscles draws the head back, sometimes even to a right angle to the trunk, so that it may appear to rest between the shoiilders. In the acute cases the retraction persists without variation for some days. As improvement sets in, the spasm is intermittently relaxed, and as the patient approaches convalescence, remarkable varia- tions are observable from day to day. In milder cases, these variations are observable from the beginning. The accompanying illustration (Plate V, fig. 2) shews the very characteristic appearance : it was taken from above on the third day from the onset; the case made a rapid recovery. The period of the disease when this sign first becomes obvious is subject to considerable variations, the second or third day being the commonest; it may, however, be delayed until the fifth or sixth. In fulminating cases retraction may be entirely absent. With this exception, however, its imiversal presence makes its appearance of considerable importance from a diagnostic point of view. Its presence is always indicative of the existence of meningitis, but, owng to its occasionally late appearance, its absence ought not to be given undue weight in the consideration of the diagnosis, and should not negative an immediate lumbar pimcture. Head retraction, in our experience, is to some extent dependent upon increased intracranial pressure; it was often greatly diminished or entirely reheved by the evacuation of a considerable quantity of cerebro-spinal fluid and the reduction of the pressure to the normal. This immediate rehef shews that it is not muscular in origin, but is dependent on irritation of the nervous elements provoked, partially at all events, by increased intra- cranial pressure. Following head retraction this rigidity may spread to other muscles than those of the neck. In a large number of cases, the condition spreads to a greater or less degree to the extensors of the 22 Symptoms [ch. spine. Rigidity of the lumbar muscles may often be noticed, and in some cases this may produce actual opisthotonos. Rigidity of the muscles of the arms and legs, notably the latter, may often be observed in a minor degree. Tonic spasm of the abdominal muscles may be noticeable, giving rise to a carinated or boat-shaped appearance of the abdomen. Rigidity of the facial muscles may be observed, which in a few rare instances reaches the degree of actual trismus. One particular form of rigidity has come into prominence under the name of Kernig's sign (Plate VI, fig. 1). Kernig of Petrograd first called attention to this phenomenon in 1884. The sign is ehcited in the following manner. While the patient is lying on his back the thigh is flexed at a right angle to the trunk. This brings the leg at a right angle to the thigh at the knee ; the thigh is now maintained in the same position by placing one hand on the patella, while an attempt is made to extend the leg upon the thigh with the other hand. When the sign is present, the spasm of the hamstring muscles prevents this extension. In a well-marked case, extension cannot be made beyond a right angle with the thigh. If any force be used, the patient at once complains of severe pain in the back. Two other methods of obtaining the sign are sometimes practised : (a) The whole leg being extended, the foot is raised into the air. As flexion of the thigh increases, it is found impossible to maintain the extension of the leg. (6) The patient's shoulders are raised from the bed. As the trunk approaches a right angle with the thighs the knees begin to flex. The most probable explanation of the sign is that traction on the inflamed lumbar nerve roots causes a protective spasm in the muscles. The accompanying illustration (Plate VI, fig. 1) shews clearly the characteristic contraction of the hamstring muscles. The appearance in a normal person is illustrated in Plate VI, fig. 2. The chnical value of the sign cannot be exaggerated. In cases of influenza and other febrile conditions, stiffness may prevent complete extension, but this in such a minor degree as to be readily distinguished from the true Kernig's sign. In cases of sciatica and lumbago extension cannot, of course, be obtained. The sign is also normal in infants up to two years of age. With these reservations, however, the sign is of the greatest value ; it occurs in all but fulminant cases, and is one of the earliest symptoms to appear. In our experience, it was slightly marked at the end of 18 hours, and fully developed at the end of 24. Consider- able inequaUty in the angle of extension may sometimes be observed nj Symptoms 23 between the two sides, presumably o'wing to more intense meningeal inflammation round the nerve roots of the one side. This sign is common to all forms of spinal meningitis from whatever cause, but it is a most valuable indication for the operation of lumbar pimcture. The other reflexes shew no particular change. The knee jerks may be absent during the more acute stage, and return with convalescence; as a rule they are present and may be exaggerated. There is said occasionally to be an extensor response in Babinski's plantar reflex, in the vast majority of cases the response is flexor. Ankle clonus has not been observed by us. The superficial reflexes are preserved, except in profoundly comatose cases. Some observers claim that the abdominal reflexes are not infrequently absent. Paresis or palsy of particular muscles is observed in a small pro- portion of cases. Of afl'ections of the ocidar muscles, strabismus is occasionally observed, the sixth nerve being the one most commonly affected. Nystagmus is somewhat more common, occurring in three out of thirty-nine cases in our experience. Diplopia occurred in about the same proportion of cases. The facial nerve is sometimes involved, though the affection is of a transitory character. The hypoglossal nerve may be afiected, but this again passes off in a short time. In one case under our care there was internal strabismus, facial palsy and deviation of the tongue, all of which passed off in a month. In this connection it is of interest to note the comparative rarity of ocular palsy compared with its frequency in tubercular meningitis, a valuable diagnostic point. These palsies disappear entirely as convalescence is estabhshed. Hemiplegia occurs, though rarely, both in the acute and chronic cases. We have found it associated wth a massive deposit of pus over the Rolandic area (Plate VII). A transient monoplegia, either of an arm or leg, is an occasional symptom, it usually passes off as recovery progresses. Flaccid paralysis of an arm or leg has been described by Horder; there is hyper-aesthesia or actual pain in the affected hmb with loss of tendon reflexes, wasting and reaction of degeneration. Recovery is usually complete. Some convalescent cases are very imsteady on their legs when first beginning to walk. This condition, according to Horder, may be associated with exaggerated knee jerks, ankle clonus and extensor response. Complete recovery usually takes place. Such symptoms were not observed in our own convalescent cases. We have, however, examined two cases at the Hitchin Con- valescent Home which somewhat closeh^ simulated Disseminated Sclerosis; the knee jerks were exaggerated, there were volitional 24 Symptoms [ch. tremors, weakness of the bladder and pallor of the optic discs. Dis- turbance of sensory nerves is marked by hyper-aesthesia of varying distribution and intensity. Two of our cases had marked hyper-aesthesia of the spine, which persisted well into convalescence. Vasomotor changes are indicated by the almost universal presence of the tache cerebrale. In addition to the affections of the ocular muscles which have been already described, the eye itself suffers in a small proportion of cases. Conjunctivitis is not uncommon, in some cases it is unilateral. The affection, as a rule, is of a mild character, though it may pass into a purulent ophthalmia. The meningococcus can be recovered from the pus. Keratitis is an uncommon complication. Flexner quotes Uhtoff, who found it occurred three times in one hundred and ten cases. Iritis and iridochoroiditis may occur, but are rare complications. Iridocyclitis leading to suppurative panophthalmitis and consequent destruction of the eyeball is the most serious complication to be feared. In the records of ninety-one cases amongst soldiers during the recent epidemic we only found this complication occur once. Morax in the Parisian epidemic observed iridocyclitis in 3 to 6 per cent. The affection would appear to be usually unilateral. The condition of the pupils is somewhat characteristic ; they are usually dilated and sluggish in their response to light. In very acute cases pin point pupils may be observed. Inequality of the pupils is infrequent, though it occurs in a small proportion of cases. As a diagnostic point it is of little value. Optic Neuritis is curiously uncommon compared with its relative frequency in other forms of meningitis. Observations as to its frequency differ markedly. Randolph of Lonaconing in Maryland found it present six times in forty cases, while Travers Smith in Dubhn found it entirely absent in thirty-six cases. In thirty cases examined ophthalmoscopi- cally by Major Cooke and ourselves at the First Eastern Hospital, optic neuritis was entirely absent. These cases were examined at all stages of the disease, and many of them more than once. In one case slight blurring of the disc was noted, which entirely disappeared in a short time. Extra fullness of the veins in hydrocephalic cases was also observed. Optic neuritis is presumably very infrequent and of little value as an aid either to diagnosis or prognosis. Primary optic atrophy is said to occur, but it is a definitely rare complication. Deafness is the most frequent affection of the special senses to be observed. The internal ear is most commonly involved, and the affection is generally bilateral. This symptom usually appears in the ii] Symptoms 25 second or third week of illness. In some cases the deafness entirely passes off as convalescence progresses. In others again it remains permanent, and may, at quite an early period, give rise to auditory vertigo. Middle ear disease is extremely rare as a complication. Two of our cases had otorrhoea long preceding the onset of cerebro-spinal fever. In one case there was deafness of the left ear, accompanied with sloughing of the right eye. The older writings on the subject are permeated with the idea that permanent impairment of the mental faculties is a sequel to be dreaded. Thus Fagge speaks of the number of imbeciles left in the wake of an epidemic in the Ehineland. Recent experience runs entirely counter to this view. During the stage of recovery patients may be morose, or unduly irritable, but those traits pass away as convalescence increases. Chronic cases are apt to become neurasthenic, and exhibit all the typical neurasthenic's power of concentration on self ; but with returning strength this attitude gives place to a normal healthy habit of mind. When there has been long and persistent headache, which is probably due to a minor degree of hydrocephalus, there is apt to be some mental enfeeblement, but if convalescence is once permanently estabhshed this is recovered from. Out of thirty-six patients sent to the Hitchin Convalescent Home, which represented all the tedious and lengthy cases drawn from the home forces, we only found one case of mental change. This man had complete loss of memory, accompanied by palsy of the right arm, suggesting a cortical lesion rather than any general cerebral degeneration. Very great improvement has since taken place both with regard to his arm and his mental condition. Rapid wasting occurs after about the fourth or fifth day in severe cases with such frequency as to constitute a characteristic feature of the disease. In patients who continue to exhibit shght though still persistent symptoms, rapid wasting becomes a striking feature. Hydro- cephahc cases, which drag on for five or six weeks, exhibit an extreme degree of marasmus, and yet there may be no difficulty in their taking nourishment, and no diarrhoea or vomiting to interfere with nutrition. It would appear probable that this wasting is essentially trophic in its nature. As symptoms abate, nutrition improves rapidly and lost flesh is soon regained. A somewhat striking feature of the malady is the complete return to health both in body and mind which is usually observed even in the most severe cases. In a small proportion of cases, arthropathies may make their appearance. The degree varies from mere pain and stiffness to acute 26 Symptoms [ch. or even suppurative arthritis. The meningococcus has been recovered from the synovial effusion. Where suppuration has occurred, there is usually a secondary infection. One joint only, as a rule, is involved, though multiple arthropathies have been observed. No joint seems to be more markedly prone to be affected than another, with the possible exception of the shoulder. A feature of these arthropathies is that, with appropriate treatment, very little pain or stiffness is left behind. It must be borne in mind that transitory arthritis may appear as a sequel to serum administration. Some observers regard nasopharyngeal catarrh as one of the earliest symptoms of the disease. Lundie, Thomas, Fleming and Maclagan, as the result of their investigations in the Aldershot Command during the epidemic of 1915, regard a naso-pharyngeal catarrh as the first stage of the disease. Their views meet with little confirmation from other observers. Of thirty- nine cases treated at the First Eastern General Hospital, two only gave a history of preceding sore throat. In the other cases, there was nothing abnormal about the throat on their admission. Further, the throats of proved carriers shew no evidence of increased catarrh other than can be accounted for by the presence of adenoids, a by no means uncommon associated condition. A notable feature of the onset of the disease is its suddenness, and the absence of any premonitory symptoms, notably the rarity of a history of a neglected cold. In acute cases, a fetid purulent discharge oozes from the mouth and throat. In other than fulminating cases, this does not occur until about the third day. Transitory aphonia has been observed, but in this case, the facial and hypoglossal nerves were also involved. Hoarseness is not a common symptom, the pharynx and larynx as a rule escaping. A shght degree of bronchitis exists in a small proportion of cases. In very acute cases, when there is profound coma and marked head retraction, ratthng in the throat and coarse mucous rales are present. Such cases are in danger of suffocation, unless the throat is swabbed out frequently. Broncho-pneumonia is a not uncommon comphcation in children, and occasionally in adults. The meningococcus has been stated to be the cause of this comphcation. There is, however, no doubt that in the vast majority of cases the affection is pneumococcal. The growth of the meningococcus from the sputum does not prove that it is the cause of the lung infection, for it may have been derived from the posterior pharynx. Lung puncture is the only method of substantiating the diagnosis. On the few occasions when this has been done, the pneumococcus has been obtained. Lobar n] Symptoms 27 pneumonia is an uncommon complication, particularly so when it is remembefed that pneumonia has been found unduly prevalent at the same time as cerebio-spinal meningitis. Pleurisy is an uncommon complication. Mention may be made of the urgent dyspnoea which arises in fulminating cases; it is, indeed, not a pulmonary but a nervous symptom, and its presence is of the gravest import. In considering the circulatory symptoms, it may be noted that in fulminating cases the extremities are cyanosed, but this sign, hke dyspnoea, is not the expression of cardiac failure, but of profoimd toxaemia, combined with lack of adequate aeration. Endocarditis is said to occur. Myocarditis leading to auricular fibrillation without valvular change occurred in one of our cases. The previous condition of the heart in this case was, however, doubtful. From the point of view of convalescence, it is remarkable what httle impress a disease so acute leaves upon the circulatory system of those who recover. Constipation is almost the invariable rule. Vomiting at the outset may be replaced by diarrhoea. One case under our care was seized at the seventh day with mucous diarrhoea, going on to the stage of passing a well-marked intestinal cast. Otherwise no sequelae are to be appre- hended in the way of atonic dyspepsia and other digestive troubles. Haematuria may occur during the acute stage, even without the presence of a purpuric rash. It has no significance with respect to any further renal complications. Sophian found pyelitis in .5 per cent, of cases in the Texas epidemic. In the last epidemic in England, in 1915, this complication was hardly ever observed. In view of the extreme frequency of retention and overflow incontinence, any observations as to the source of pus in the urine would require most searching investi- gation. CHAPTER III DIAGNOSIS Importance of early diagnosis. Early signs, indicating lumbar puncture. The operation of lumbar puncture. Advisability of anaesthesia. Effect of puncture on blood pressure. Differential diagnosis from influenza, from pneumonia, from typhoid fever, from typhus fever, from malignant exanthemata, from tonsillitis and pharyngitis, from tetanus, from tubercular meningitis, from other forms of purulent meningitis, from cerebral abscess, from thrombosis of lateral sinus, from meningeal haemorrhage, from poliomyelitis, from acute myelitis and from delirium tremens. The value of a diagnosis is largely enhanced when it leads to prompt and efficient treatment. The literature of earlier epidemics of meningitis has handed down a store of clinical observations of great value, whereby an accurate diagnosis may be accomplished. Such a diagnosis is based on the appearance of certain symptoms, on their relative severity and on their sequence in point of time. It must be stated at the outset that a diagnosis based on clinical evidence alone cannot be conclusive, more especially in the early stages. As will be shewn later, treatment is capable of exerting a vital effect, and the date at which it is begun is of great moment. Two discoveries of recent years have profoundly modified the outlook as to early diagnosis. Of these the first was the discovery of the meningococcus by Weichselbaum in ] 887 ; the second the introduction of lumbar puncture by Quincke in 1890. With perfection of the technique of lumbar puncture it became possible to recover the meningococcus from the cerebro-spinal fluid at an early stage of the disease. An early diagnosis and the institution of specific treatment are thus secured by one and the same procedure. The question to be determined, therefore, is what cardinal symptoms are sufficiently suggestive of the disease to justify the immediate per- formance of lumbar puncture. A sudden onset, probably accompanied bj' a rigor, headache gradually increasing in intensity, and vomiting occurring within the first twenty-four hours, point towards meningitis, but are common to other infections. The absence of herpes or a macular OH. Ill] Diagnosis 29 rash, is of slight value : these do not appear until the third to fifth day, and to wait for confirmation from their appearance might mean fatal delay. The presence of a petechial or purpuric rash, which may appear in the first twenty-four hours, leaves so little doubt as to justify immediate lumbar pimcture. Haemophilia must be excluded, as lumbar puncture has been performed on a case of this disease with meningeal haemorrhage, the difficulty in arresting bleeding first calling attention to the true nature of the case. Head retraction is variable in the date at which it makes its appearance, and much stress should not be laid on its absence. The cervical muscles should be carefully examined for any tenderness or stiffness; if this is present, the probability in favour of meningitis is increased. The value of Kernig's sign in all adult cases cannot be over-estimated. This value lies firstly in the date of its appearance, — it may be only slightly marked at the end of eighteen hours, but is usually fully developed at the end of twenty-four; and secondly in the fact that it is never present in its fidly- marked form in other affections liable to be mistaken for meningitis. Kernig's sign is common to all forms of meningitis of whatever origin, but its presence is a powerful factor in determining the necessity for immediate lumbar puncture. Retention of urine is an important symptom to be taken into account. It occurs in a large proportion of cases, many of which are comparatively mild ones. Further, it may make its appearance at the end of twenty-four hours, and is an uncommon symptom at this early stage in other febrile affections. The presence of this symptom should be given great weight in estimating the relative values of the clinical aspects of the case. Early delirium, especially when associated with the persistence or indeed aggravation of the headache, tends further to differentiate the case from other acute infections. To sum up: a patient who has been seized with sudden illness ushered in by a rigor, accompanied by severe headache rapidly growing worse and soon accompanied by vomiting, may be regarded as a suspicious case. When Kernig's sign is present, and there is some pain and stiffness of the muscles of the neck, and if retention of urine occurs, the probabilities are sufficiently great to justify lumbar puncture. Delirium going on to coma, the presence of a petechial rash, or of head retraction, would merely confirm these probabilities. Before discussing the differential diagnosis of epidemic meningitis, the operation of lumbar puncture may most conveniently be described. Lumbar puncture was first performed by Corning, in America, in 1885 for the purpose of injecting cocaine into the theca. In 30 Diagnosis [cii. 1891 Wynter published four cases thus treated for the relief of tubercular meningitis. Quincke worked out the technique of the operation, and it is largely due to his advocacy that it has come into general use. The anatomical conditions, which make lumbar puncture possible, are the width of the inter-vertebral foramina in the lumbar region. These foramina are large and triangular in form, measuring one-third of an inch across, and being covered in by the ligamenta subflava. Further, below the fourth lumbar vertebra the conus medullaris ceases, and the vertebral canal is occupied only by the Cauda equina. By traversing a comparatively thin layer of the lumbar muscles, it is thus easy to pass a trocar and cannula into the spinal canal below the level of the cord. Considerable diversity of opinion exists as to the advisability of giving a general anaesthetic. The American writers, Sophian and Heiman and Feldstein, regard a general anaesthetic as entirely unnecessary. Sophian has advocated an ingenious method of distracting the patient's attention by what he terms water anaesthesia, which consists in the patient sucking water through a straw during the operation, and thus distracting his attention. It is, of course, only a variant of the old naval trick of biting on a bullet. Robb, who has tried it in this country, has been disappointed with its efficacy. Border regards general anaesthesia as infinitely preferable to local, an experience which is endorsed by Robb. Our own experience is entirely in favour of a general anaesthetic, and for the following reasons. In the first place, it is obviously necessary when there is active delirium; it would be impossible to keep the patient in the requisite position long enough to perform the puncture and run off the full quantity of fluid. There is, moreover, always the very definite danger of the patient in his struggles breaking the needle short off inside the vertebral canal. For the full completion of the operation, it is essential that as much fluid as possible should be run ofl; when this is attempted with a strugghng patient, the result is apt to be an object lesson in the futihty of half-measures. A further point is that, when lumbar puncture has to be repeated day after day, it would impose an entirely unnecessary strain on the fortitude of the patient. With an anaesthetic patients are in our experience perfectly willing for the operation, and indeed when suffering are eager for it. When headache is severe it is no uncommon thing to see a patient, who had previously been restless and moaning, pass straight from the anaesthetic to a peaceful sleep of four or five hours. The argument against an anaesthetic is naturally that it is exposing the ni] Diagnosis 31 patient to a further danger, which, the minor character of the operation does not warrant. The considerations which should weigh against this view have been stated. Our own experience was that in 276 successive lumbar punctures no untoward symptom was experienced except in two cases. One of these was a case of multiple cerebral abscess brought in unconscious but restless, in which respiratory failure occurred directly after the evacuation of the fluid. The probable reason for this was found post-mortem to be the presence of a large cerebellar abscess, which the withdrawal of fluid allowed to press on the floor of the fourth ventricle. Obviously, death in this case can hardly be attributed to the anaesthetic. Another case of pneumococcal menin- gitis was admitted delirious and struggling, and died of respiratory failure fifteen minutes after the operation. In both these cases, lumbar puncture was imperative and in both its performance would have been impossible without an anaesthetic. With these two exceptions the operation under an anaesthetic, often undertaken when the patient's condition seemed desperate, never jier se gave rise to a single untoward symptom. In all ordinary cases, the administration of a general anaesthetic would appear markedly to faciHtate the operation, and to be practically free from danger. It must be borne in mind that some acute cases die of sudden respiratory failure ; and the fatal event might appear to be hastened by the administration of an anaesthetic. The general restlessness and rigidity of the lumbar muscles which these patients commonly manifest would render lumbar puncture a very diflicult matter. Local anaesthesia in our own hands was useless in deUrious cases, and did not obviate rigidity or restlessness in mild ones. Ether is on theoretical grounds and judged by practical results the best anaesthetic. Owing to the open-air wards in which our cases were, the chloroform and ether mixture was found more convenient and equally safe. Theoretically the increase of intracranial pressure due to the anaesthetic, enables more complete drainage to be performed. Elaborate apparatus is entirely unnecessary for the performance of lumbar puncture. The best type of needle is that devised by Mr Arthur Barker. It has the merit of sufiicient stiffness, the head is of good size and fits easily into the palm of the hand, and the slot which engages the trocar is easily manipulated. Should no special needle be available, any trocar and cannula which is more than three inches long will serve perfectly well. The trocar must be sharp, as with a blunt point there is always the danger of pushing the dura mater in front of the needle. The instruments should be boiled. It is advisable 32 Diagnosis [ch. that the operator should wear gloves. The skin is best disinfected by painting with iodine or by washing with soap and water and rubbing with ether or alcohol. The patient should be placed on his side, so that his buttocks are just at the edge of the bed. The knees are then flexed upon the abdomen so that the thighs are in contact with the abdominal wall. The head and trunk are bent forward, i.e., towards the centre of the bed, and all pillows are removed from the head and neck. By this manoeuvre the whole spine is flexed, the inter-vertebral foramina are opened to their fullest extent, and the ligamenta subflava are rendered tense and more easily pierced. The exact position of the patient is a matter of great importance, and one of the main sources of failure is carelessness in this respect. The puncture should be made in the inter-vertebral foramen between the fourth and fifth lumbar vertebrae. The spine of the fourth lumbar vertebra is cut by a vertical line which joins the summits of the two crista ilii. These two spots should be carefully marked out, and the broad flattened spine of the fourth lumbar vertebra will be readily felt in the line which joins them. Below the spine the inter-spinous space will be felt, varying in length from half an inch in children to one and a half inches in adults. The seat of puncture having been determined, the theca can be reached by two routes, the median and the lateral. The merit claimed for the median operation is that deviation of the point of the needle is less likely to occur as the path is a direct one. On the other hand, in adults the stout inter-spinous ligament has to be traversed, an operation which seriously interferes with the tactile sensations of the operator, which form such an important factor in the success of the operation. The advantage of the lateral method is that none but soft structures are traversed until the ligamentum subflavum is reached, thus ensuring greater dehcacy of manipulation. The drawback, as before stated, is the possibiHty of the point of the needle being directed at a wrong angle, an initial error which becomes magnified as the depth of the puncture increases. In children the median operation would appear to be the more easily performed. In adults, however, a considerable experience amongst soldiers has led us to the conclusion that the lateral operation confers such advantages in the way of delicate manipulation as to make its selection advisable. The lateral operation is thus performed: the needle is held with the butt resting in the hollow of the palm, the shank steadied by the forefinger and thumb. A point is then selected mid-way between the fourth and fifth lumbar spines, a quarter of an inch laterally to the Ill] Diagnosis 33 middle line, and preferably on the dependent side. The skin is steadied by the forefinger and thumb of the left hand. The needle is pushed towards the middle line, forwards and shghtly upwards. Should the needle impinge upon bone, it must be slightly withdrawn and the point directed lower down. If no bone is encountered, the point of the needle is felt to pass through the ligamentum subflavum, which gives the sensation of piercing gristle, and then through the dura mater. The piercing of the dura mater has an entirely different feel, which has been described as being like passing a knitting needle through sacking. When the dura mater has been pierced, the needle can be felt free in the theca. If the point is still further pushed on, it can be felt to strike the body of the vertebra, a manoeuvre which should whenever possible be avoided, on account of the danger of wounding the anterior longitudinal veins. The depth to which the needle must be introduced so as to reach the theca varies from three inches in the adult to one inch in children. Methods of measuring the depth to which the needle penetrates have been devised, but found in practice to be an entirely useless encumbrance. When the point of the needle can be felt free in the theca, the trocar should be withdrawn; this will usually be followed by a flow of cerebro-spinal fluid. Should no fluid flow, the probability is that the needle is either not in the theca, but has merely pushed the dura mater in front of it, or has struck a nerve. The trocar should then be re-inserted, and the needle gently moved backwards and forwards; in the event of no fluid escaping after this manoeuvre the needle must be withdrawn, and a fresh puncture made in another place. Except in advanced hydrocephalic cases, there is probably no such thing as a "dry tap." and reaching the theca is only a matter of perseverance. The same cautions apply to the median operation, except that the puncture is made directly forwards in the middle hne. Those who are performing the operation for the first time should remember that the operation is an extremely easy one, provided first that due care is exercised as to the exact position of the patient, and secondly that the landmarks are accurately ascertained. Given that these two requirements are satisfied, very little manipulative skill is required to ensure success. As the fluid escapes, a note should be made of the pressure at which it flows and of its general characteristics. Should it be very thick and purulent, it may be necessary to clear the cannula by inserting the trocar. After the first few drops the fluid should be collected in a sterile test tube for bacteriological examination. As a rule, the fluid should be allowed to flow until it reaches the normal F. & G. 3 34 Diagnosis [CH. rate, which is estimated at one drop to every two or three seconds. The needle is then gently withdrawn, and the puncture covered with gauze and collodion. The cUnical experience of many observers has made it clear that the removal of a considerable quantity of fluid is not attended with any alarming symptoms from the sudden lowering of cerebro-spinal pressure. Manometers have been devised by Quincke, Kroenig and Crohn, whereby the decUne in cerebro-spinal pressure may be gauged, and the operation stopped in case of any sudden fall. Careful observations as to pulse and respiration in some hundreds of operations have convinced us that no appreciable shock or collapse is met with, if the fluid is allowed to run until it reaches its normal rate. Sophian gives a series of observations on the changes in blood pressure during the evacuation of cerebro-spinal fluid. In two-thirds of the cases the blood pressure fell from 3-10 millimetres during the operation ; in a few it was raised 2-12 milhmetres ; in the rest unchanged. Sophian concludes that the evacuation of fluid in considerable quantity has no marked effect on the blood pressure. There would appear to be no evidence that the removal of large quantities of fluid by lumbar puncture is attended with danger. Some observers have removed three to four ounces. We have constantly removed between two and three oimces without the appea.rance of any symptoms which might cause alarm. The differential diagnosis of cerebro-spinal fever is mainly concerned in distinguishing the disease from acute febrile infections on the one hand, and other diseases of the brain and meninges on the other. The chief febrile diseases are influenza and pneumonia, while the chief cerebral affections are meningitis due to other organisms, and cerebral abscess multiple or single. The diagnosis of early cases of cerebro-spinal fever from influenza presents some difficulty. In both there is a sudden onset accompanied by headache and fever. In both pain and stiffness in the neck as well as in the back and legs are prominent symptoms. In cerebro-spinal fever the first two days, even of an attack which ultimately becomes severe, may present no obvious difference from those of a case of influenza. The points to be noted are that the headache in cerebro-spinal fever usually increases day by day, and when vomiting appears a day or two after the onset without diarrhoea, the case may be regarded as suspicious. Gastric influenza is rarely unaccompanied by diarrhoea. In influenza again search for Kernig's sign may reveal some stiffness of the legs, which prevents full extension of the knee. Equivocal as m] Diagnosis 35 this sign may appear, the stiffness of influenza remains the same from day to day, while in cerebro-spinal fever it becomes rapidly more marked until the fully-developed Kernig is obtained. Retention of urine is in favour of cerebro-spinal fever. The most likely source of error is that, in the absence of an epidemic of cerebro-spinal fever, the latter disease may not be thought of until a marked exacerbation of cerebral symptoms occurs. Much valuable time may thus be lost before treat- ment is begun. When, on reviewing the chnical signs and symptoms, their relative value appears evenly balanced, lumbar puncture should be performed. In this connection we have met with several cases apparently of influenza, in which the severity of the headache appeared to justify lumbar puncture. Perfectly normal cerebro-spinal fluid was drawn off, which however ran at considerable pressure, with remarkable relief to the headache. Mild cases of cerebro-spinal fever may be unrecognized, and classed as influenza, but no proof exists that the former disease is ever so shghtly marked as not to develop at least some of the diagnostic signs. At the onset pneumonia may easily be confounded with cerebro- spinal fever. This is notably the case in children and young adults, in whom headache, and with it vomiting, may be striking symptoms in the first few days. Physical signs are usually absent at this stage. A rise in the pulse respiration ratio, which does not fluctuate from hour to hour, together with the absence of Kernig's sign, are all in favour of pneumonia. Should physical signs of consolidation not appear, and the cerebral symptoms tend to increase, lumbar puncture should be undertaken. In this connection we would point out that two cases have been admitted into our ward in a hydrocephalic state, the long-past acute stage of whose disease had been considered through- out to be pneumonia. The meningococcus was proved to be present in both by lumbar puncture. The continuous headache and fever of the first week of typhoid may give rise to some doubt. The sudden onset of meningitis as compared with the gradual exacerbation of typhoid are points to be borne in mind. Sir William Jenner used to say, "in typhoid headache ceases when delirium begins, whereas in meningitis the two co-exist." This clinical fact should be given great weight. The presence of Kernig's sign, of rigidity of the neck, and possibly of bladder symptoms would help in decision. It is very rare for a case of cerebro-spinal fever to remain febrile so long as to suggest typhoid, without one or other of these symptoms becoming manifest. The characteristic steady 3—2 36 Diagnosis [ch. remittent rise of typhoid fever is hardly ever observed in cerebro- spinal fever. In the latter disease, the temperature chart is usually very irregular and frequently intermittent. After the first week, Widal's reaction would be decisive. The distinction of typhus fever from cerebro-spinal fever, par- ticularly during the early days, is a matter of some difSculty. In both there is a sudden onset with an initial rigor, with headache increasing in intensity and followed by delirium. Retention of urine may arise early in typhus, further confusing the clinical aspect of the case. The appearance of the patient presents points of similarity; in both the expression may be dull and heavy, with that curious and haunting expression as though watching a phantasmagoria. The points of difference to be noted are that delirium comes on much later in typhus, and head retraction is absent. In typhus moreover the pupils are contracted, in cerebro-spinal fever usually dilated. A petechial rash occurring early is in favour of cerebro-spinal fever, when appearing later its significance is equivocal. In any case where the symptoms are of such gravity as to suggest the presence of typhus, the point should be settled without delay by lumbar puncture and bacteriological examination. The malignant forms of scarlet fever, measles, small-pox and mumps are liable to be confused with fulminating cases of cerebro-spinal fever. The urgency of the symptoms would point to immediate lumbar puncture as the only method of estabUshing a diagnosis, and holding out any hope of benefit. It must further be remembered that cerebral symptoms may occur later, in both measles and mumps. This complica- tion, however, arises late rather than early in the disease, and the previous history would be a decisive factor in forming an opinion. The absence of proof that the meningococcus can cause an acute affection of the throat has already been insisted upon. But as this view is still widely held, cases of tonsiUitis and pharyngitis may come under observation as suspected cerebro-spinal fever. Beyond the frequently severe onset with rigor, further similarity is singularly lacking. An attack of influenza, pneumonia, or any of the specific fevers, may be followed by cerebro-spinal fever as a distinct infection during convalescence. An epidemic of measles occurred in the Highland Territorial Division in the Eastern Counties during the winter of 1914-15. One man who came under our charge had been afebrile for sixteen days after an attack of measles; he suddenly developed ni] Diagnosis 37 cerebral symptoms, from -which he died. The meningococcus was recovered from his cerebro-spinal fimd. The common presence of muscular rigidity and some degree of opisthotonos are possible sources of error and may give rise to a suspicion of tetanus. In tetanus, however, the mind is absolutely clear, and the general constitutional symptoms are slight. Trismus is extremely rare in cerebro-spinal fever, its absence is thus a diagnostic point of considerable importance. The main difficulties in differential diagnosis are met with in distinguishing cerebro-spinal fever from other diseases of the brain and cord. In the case of other varieties of meningitis, in particular, the pathological condition may give rise to symptoms chnically identical with those of cerebro-spinal fever. Of these tubercular meningitis is far the commonest. The first point of difference to be noted between the two diseases is the character of the onset. The onset of tubercular meningitis is marked by a gradual failure of health, accompanied by headache slowly increasing in intensity. The tempera- ture is but shghtly raised, and photophobia is a marked symptom. In cerebro-spinal fever, on the other hand, the onset is sudden, the temperature is raised, the headache rapidly increases in intensity and dehrium comes on early. Photophobia, common in tubercular menin- gitis, is rare in cerebro-spinal fever. Paralysis of one or other of the ocular nerves is far more often observed in tubercular meningitis than in cerebro-spinal fever. A definite diagnosis is, however, only possible by the examination of the cerebro-spinal fluid. The fluid in tubercular meningitis contrasts with that of cerebro-spinal fever in the com- paratively small number of cells present, and the preponderance of lymphocytes which form 70-100 per cent, of the total. In cerebro- spinal fever the lymphocytes are comparatively few in number, seldom amounting to 30 per cent.; polymorphonuclear cells comprise the bulk of the deposit. The identification of the meningococcus in film or culture clinches the matter. The fluid from a hydrocephahc case may give rise to considerable difficulty, if the case has not come under observation in the acute stage, for it occasionally happens that the cytological picture is identical with that of tubercular meningitis. The cells are present in small numbers, the lymphocytes form 70 per cent, or more of the total. An additional difficulty is that the detection of the meningococcus in film or culture is often impossible. The identification of the tubercle bacillus in the fluid is usually a matter of extreme difficulty, consequently its absence is of sHght diagnostic 38 Diagnosis [cH. value. The diagnosis between the hydrocephalic stage of cerebro- spinal fever and tubercular meningitis may therefore rest entirely on the pre^dous history and the nature of the onset. Purulent meningitis may occur as the result of infection by any of the pyogenic group of bacteria. The pneumococcus is one of the commonest causes of a primary meningitis of this kind. The chnical signs are largely identical with those of cerebro-spinal fever, except that the course and development of symptoms proceed at a more rapid rate than in the latter afiection. This rapid march of symptoms, coupled with their extreme gravity, renders lumbar puncture imperative, without waiting for any further developments to aid in diagnosis. Pneumococcal meningitis is usually secondary to a pneumococcal in- fection elsewhere, it may be in the lung or middle ear, but may also form part of a general primary pneumococcal septicaemia. In long-standing hydrocephalic cases of cerebro-spinal fever there may be a secondary terminal infection by the pneumococcus. The onset of streptococcal meningitis is often somewhat obscured, as meningitis is usually secondary to a focus of infection elsewhere, most commonly about the middle ear. The course is more rapid than that of cerebro-spinal fever. The symptoms are those of spinal meningitis in general, and a diagnosis can only be arrived at by bacteriological examination after lumbar puncture. Staphjdococcal meningitis is very rare, when it occurs the symptoms are those of spinal meningitis and are indistinguishable chnically from those of cerebro-spinal fever. Lumbar puncture and bacteriological examination afford the only means of ascertaining the infecting organism. The course of the disease is very rapid, lasting from three to five days, and leading invariably to a fatal result. The meninges in this infection are involved secondarily to some focus existing else- where in the body. One case which came imder our care was admitted with all the symptoms of cerebro-spinal fever; staphylococcus aureus was grown from the lumbar puncture fluid. Post-mortem marked purulent meningitis was found. Cultures of the heart's blood, the meninges, the lung and the pleura all grew a pure culture of staphy- lococcus. The only source of this general staphylococcal septicaemia was a small ulcer in the anterior fold of the axilla. Cerebral abscess may give rise to symptoms closely simulating those of cerebro-spinal fever. Such abscesses may be single or multiple. The solitary abscess is usually associated with disease of the middle ear. The onset is sudden and is characterized by headache and vomiting, accompanied by fever. The headache in cerebral abscess is usually in] Diagnosis 39 unilateral and tends to lessen in intensity, in contradistinction to that in epidemic meningitis, which increases in severity. Optic neuritis is frequent in cerebral abscess, rarely observed in cerebro-spinal fever. The presence of any local affection of the ear is strongly in favour of cerebral abscess. The differential diagnosis becomes exceptionally difficult if the cerebral abscess spreads to the base of the brain and down the cord. Lumbar puncture then yields a purulent fluid, resembhng closely that obtained in cerebro-spinal fever. Such a combination of lesions reproduces accurately the symptoms of the latter. The presence of Kernig's sign under these circumstances renders diagnosis by other than bacteriological means sometimes impossible. , A case came under our care in which no external signs of ear disease were present, and lumbar puncture yielded a purulent fluid at considerable pressure. No organisms were identified with certainty in films, and no growth was obtained in culture, though three separate puncture fluids were sown. It was therefore thought possible that the patient was suffering from cerebro-spinal fever due to a meningococcus which was difficult to grow on artificial media. Post-mortem there was a simple abscess in the temporo-sphenoidal lobe, with necrosis of the petrous portion of temporal bone. The abscess had spread to the base of the brain, and a purulent meningitis was present here and throughout the length of the cord (Plate X, fig. 4). Film preparations from the abscess shewed streptococci in short chains and fusiform bacilli. Neither of these organisms could be grown, though various media were tried. The simulation of cerebro-spinal fever is thus practically complete in a case of this kind. Multiple abscesses of the brain are frequently secondary to septic injuries under the aponeurosis of the scalp. Such a condition gives rise to symptoms which are chnically indistinguish- able from those of soHtary abscess. In a case under our care, the only external sign of injury was a small locahzed swelhng lying deep to the occipital muscle. Thrombosis of the lateral sinus also gives rise to acute cerebral symptoms. The character of the temperature and the constant repetition of rigors are usually sufficiently marked to indicate the pyaemic nature of the condition. Meningeal haemorrhage may present such similarity to cerebro- spinal fever as to make its exclusion a matter of some difficulty. A history of coma without previous delirium or an initial rigor would exclude all but fulminant cases of cerebro-spinal fever, whose recognition should present no difficulty. A raised temperature is in favour of 40 Diagnosis [ch. hi cerebro-spinal fever. The presence of hemiplegia at so early a stage would be in favour of meningeal haemorrhage. Poliomyehtis may occasionally present some difficulty in children. As a rule, the constitutional disturbance is so shght and the palsy becomes manifest so soon as to make the distinction easy. In the more acute form, which is often epidemic, the onset may simulate cerebro- spinal fever. The early occurrence of locaUzed palsies or of hemiplegia is the chief distinguishing point. In the cerebral type known as pohoencephahtis these may, however, be absent. The latter form is invariably ushered in by a convulsion, which is a comparatively un- common event in cerebro-spinal fever. In cases of doubt, the diagnosis can be determined by bacteriological examination of the lumbar puncture fluid. Acute anterior poliomyelitis has a seasonal prevalence very different from that of epidemic meningitis, occurring chiefly in the summer and autumn. Acute myehtis, if accompanied by fever, may be mistaken for cerebro-spinal fever. But the complete absence of cerebral symptoms and the presence of signs of localizing lesions in the cord renders differentiation easy. Cerebro-spinal fever in the acute stage may be mistaken for delirium tremens. A careful examination will shew signs of definite affection of the nervous system in cerebro-spinal fever, which will suffice to differentiate the two conditions. CHAPTER IV ACUTE FORMS Classification. Fulminating form, an acute meningitis not a septi- caemia. Netter's ambulatoi'y type, Sophian's accumulative stage. Acute fatal type. Acute type with recovery. Abortive forms. The acute onset of cerebro-spinal fever has already been described, and is to a greater or less degree practically universal. The subsequent course varies, but allows of a rough separation of cases into two classes ; the acute, in which either death occurs or the patient is on the way to convalescence in about a fortnight, and the sub-acute and chronic, in which the issue is in doubt for a longer period. The acute class will be dealt with in four categories : Fulminating ; Acute fatal cases; Acute cases which recover; Abortive cases. The name fulminating or foudroyant has been apphed to those cases which begin with startling suddenness and run a uniformly rapid course terminating in death in twenty-four to thirty-six hours. The whole aspect of these cases is one of a profound toxaemia, analogous to the mahgnant forms of the acute exanthemata, and recalUng \ividly the hterary descriptions of plague. The onset may be startHngly sudden, in some cases the patient falls down in the street, and is picked up comatose. A man may be in his ordinary health the night before, and be found unconscious or even dead in bed in the morning. The onset is occasionally marked by a convulsion, and convulsions may occur during the brief course of the disease. More often there is a rigor followed immediately by intense headache and vomiting, this again rapidly succeeded by dehrium passing quickly into coma, the whole sequence of these events occupying only four or five hours. The stage of delirium may last longer and assume a violent or even maniacal form before coma supervenes. Vomiting occurs in those cases in which consciousness is not lost at the onset. Within a few 42 Acute Forms [CH. hours a true purpuric haemorrhagic rash may make its appearance. The blotches may be as big as a plum, and are scattered indiscriminately over the body, the face being frequently involved; they are usually of a deep grape colour, and may occasionally take on a bullous character. Plate IV, taken from a case which died within twenty- four hours of being found unconscious in bed, well illustrates this purpuric rash. In other cases a petechial rash appears early, distributed over points of pressure. The face may be either pale or cyanotic and bathed in sweat; the hands are blue and tremulous. Subsultus tendinum is usually present. Dyspnoea is a striking symptom; the respirations are rapid and shallow, while the patient beats the air with his hands in a vain struggle for breath. The respiration may assume the Cheyne-Stokes rhythm. The temperature is usually not markedly raised, being under 100 or sometimes subnormal. The pulse is feeble and fluttering, quickened not slowed, and may be irregular. There is always retention of urine. Head retraction and muscular rigidity are generally absent; it would appear that the disease kills the patient before these signs have time to develop. On the other hand Kernig's sign is generally present even at an early stage. Netter calls attention to the possible medico-legal aspect of these cases. Thus a patient suddenly attacked may fall in the street and fracture his skull, a source of confusion which should be borne in mind. The occurrence of vomiting, followed by rapidly oncoming coma, may again give rise to suspicions of poisoning. A careful estimate of the symptoms and signs should avoid error in this regard. Considerable diversity of opinion has been expressed as to the nature of this form of the disease. It is held by some that it is essentially an invasion of the blood by the meningococcus, a true meningococcal septicaemia. Others again maintain that death is brought about by the intensity of the meningeal inflammation. That a true meningococcal septicaemia can occur is proved by a case reported by Andrewes in 1906. A medical man was attacked with symptoms of fulminant purpura. Blood examined in film preparations, drawn from the basilic vein shortly before death, was found to contain large cocci exclusively intracellular, enclosed in pairs or groups of half-a-dozen, rarely more, in the polynuclear leucocytes. The blood yielded a pure culture of a gram negative coccus, which examination proved to be identical with the meningococcus. This patient exhibited no symptoms of meningitis during life, and post-mortem there was no evidence of meningitis even on microscopical examination; there were haemorrhages in the rv] Acute Forms ' 43 sub-arachnoid space as elsewhere. This case estabhshes beyond doubt the occurrence of a true meningococcal septicaemia. Netter refers to cases in which the cerebro-spinal fluid is clear, and in which post-mortem, beyond marked engorgement of the vessels, the meninges appear normal, with the exception that the pia mater at the level of the cisterna pontis, is opalescent and lustreless. jMicroscopical examination of the meninges at this level shews a polynuclear infiltration and meningococci. Netter regards these cases as shewing that the patients were killed by septicaemia before the pathological lesions of the brain had time to become fully developed. Cases presenting such pathological conditions he names true fulminating cases, as opposed to those in whom purulent meningitis is found, which are classified as ambulatory cases with a terminal fulminating stage. In this con- nection it may be pointed out that the naked eye appearance of the cerebro-spinal fluid is a fallacious guide to its pathological properties. Examination of a centrifugalized fluid will often materially alter the evidence furnished by naked eye inspection alone. Sophian conceives that during the earlier hours of the disease the meningococcus is circulating in the blood stream, before ahghting on the meninges and setting up an inflammatory process. This phase he designates the "accumulative stage." No clinical or pathological evidence is adduced in support of this view, and the observations from other sources are so conflicting that the common occurrence of such a stage remains a matter of theory. The evidence in favour of a true septicaemia is based on one undoubted case of Andrewes', and Netter's cases in which death occurred before meningitis had reached a purulent stage. A few similar cases have also been reported from Germany. Other pathological observations, however, put a different aspect on the question. Purulent meningitis may be observed in cases which have been fatal at a very early stage. Netter speaks of the astonishment with which he has viewed the purulent aspect of the meninges, in contrast with the short duration of the symptoms. In our own experience we have foimd purulent cerebro-spinal fluid five hours after the patient had been found imconscious in bed. In this case, in which the patient died in twenty-four hours from the time of being found unconscious, there was well-marked purulent meningitis of the vertex and cord. Another case yielded purulent cerebro-spinal fluid at the end of twenty-four hours, and well-marked purulent meningitis was foimd at the end of thirty-six hours. In a third case, which was found dead in bed, purulent meningitis was found post-mortem. As this man had been doing 44 Acute Forms [ch. duty the night before, the whole course of the disease cannot have been more than twelve hours, and yet in this short time the essential anatomical lesion of the disease had been evolved. Netter explains these cases on the hypothesis that they are ambulatorv cases with a fulminating terminal stage. This author contrasts these with the septicaemic type presenting slight meningeal changes, wliich he regards as the true fulminating type of the disease, while the ambulatory cases are but its cHmcal coimterfeit. The theory of an ambulatory stage would require a considerable weight of ehnical observation to sub- stantiate it. which is hitherto lacking. There are moreover reasons for doubting its probable existence. In the first place a notable feature of cerebro-spinal fever is its sudden onset in persons who appeared to be in their ordinary health. A review of the histories of a con- siderable number of cases reveals no prolonged period of malaise in any way comparable to the ambulatory form of typhoid. Further all the fulminating cases, which came under our care or witliin ovii knowledge, . were at duty within a few hovirs of being attacked. The conclusion would appear to be that in the majority of cases, at all events, the meningococcus is capable of producing the essential anatomical lesions of the disease in a siirprisingly rapid manner. From this it would be fair to asstune that death is due rather to the intensity of the pathological process than to any general infection of the blood stream. The view that we are at present inclined to uphold is that the true fulminating tA'pe of the disease, as most commonly met with, is an acute and very violent form of a true infection of the cerebro- spinal system. A septicaemic form of meningococcal infection does occur rarely, but it essentially differs both clinically and pathologically in furnishing no evidence of disease of the meninges of the brain and cord. Again, in the septicaemic form the cocci can easily be found in the blood, while in the fulminating form of meningitis positive blood cultures can only occasionally be obtained with great difficulty. In the acute fatal type the onset is sudden, the usual history is of a feeling of indisposition with distaste for food, which may last for an hour or two and is then followed by a rigor. With or even before the rigor headache begins and rapidly increases in intensity. The temperattire rises to 101-103 and with varying remissions remains at this level. Within the first twelve hours vomiting occurs; this may be only transitory, or be continuous and very distressing. Xausea is usually not a marked symptom. In from twelve to thirty-six hours iv] Acute Forms 45 delirium begins. This at first is not continuous, but mainly nocturnal, and the patient can usually answer a question perfectly sensibly. As dehrium becomes more marked, the patient becomes restless, constantly fumbhng with his hands and trying to get out of bed. During the second day, mere muttering may give place to noisy and sometimes maniacal delirium. In the course of the second day a petechial rash may make its appearance, distributed over points of pressure, such as the knees, elbows, shovilders and malleoU. The appearance of this rash is evidence of a severe toxaemia, to -which doubtless some of the cerebral manifestations are due. The presence in the post-mortem room of particularly dense collections of pus, which during life have given rise to a definite train of nervous symptoms such as localized convulsions or hemiplegia (Plate VII), suggest that the toxic effect from the exudate on the subjacent nervous tissue is severe. In addition, however, the increased intracranial pressure plays a part in the production of the symptoms. An evanescent erythematous rash may appear at any time in the course of acute symptoms. At the same time pain and tenderness at the back of the neck are noticeable, and head retraction begins to develop. Kernig's sign can usually be obtained early in the second day. During the second or third day retention of urine occurs in a considerable number of cases. The symptoms during the second day may not only have undergone no aggravation, but may even considerably diminish in intensity. A recognition of this is a matter of the utmost importance as the apparent amehoration may seem to warrant a purely expectant attitude. The postponement of lumbar puncture at this stage may determine the ultimate issue of the case unfavourably. With the beginning of the third day a definite . change takes place ; the muttering delirium gives place to profound coma, or to maniacal delirium with great restlessness, head retraction is increased, retention of urine is complete. At the same time the respiration is frequently hurried and irregular in rhythm. This irregularity may present the imdulatory type in which paroxysms of rapid or shallow breathing alternate at longer or shorter intervals with the normal respiratory rhythm. Another type of respiratory irregularity is that associated with the name of Biot, which is characterized by periods of apnoea which occur at varying intervals. Deep sighing is most commonly observed accompanying this type. Biot's type of breathing is a famiUar phenomenon in tubercular meningitis, its occurrence in cerebro-spinal fever is of equally grave import. Connor and Stillman took tracings from several himdreds 46 Acute Forms [ch. of cases suffering from different diseases, and in only one case suffering from meningitis was this form of arhythmia observed. Cheyne-Stokes breathing is not usually observed except at the near approach of death. The cerebro-spinal fluid at this stage always runs at high pressure, and is usually purulent in appearance; its micro- scopical characters are described elsewhere. With this deepening coma occurring on the third or fourth day there may be mucus rattling in the throat, partly due to coma, but probably also to the position of the windpipe, owing to the extreme retraction. A fetid discharge may ooze from the mouth and nose. In some cases the power of swallowing is entirely lost, while in others it is retained. Incontinence of urine and faeces may occur, but more commonly there is absolute constipation and retention of urine. With the advent of the fourth day the symptoms assume a still graver aspect. The coma deepens, the breathing becomes more hurried, the hands are cyanotic, and the body is often bathed in sweat. Herpes may appear on the lips or elsewhere on the fourth day, and a macular rash on the extremities, though this is an uncommon phenomenon in fatal cases. Convulsions may appear at this stage, or hemiplegia become manifest: both phenomena are found associated with locahzed purulent deposits on the cortex leading to compression. The aggravation of symptoms on the third day cannot be due merely to an increased toxaemia, but is to be explained by the establishment of compression of vital nervous structures by increased intracranial pressure. Lumbar puncture, with the removal of large quantities (two ounces or more) of cerebro-spinal fluid or with the injection of serum, brings no alleviation of the symptoms. In our experience lumbar puncture was rarely performed in these cases before the third day, owing to the difficulty ■ of getting the patients sent to hospital from billets earlier. Lumbar puncture was thus undertaken at a period when as a rule the symptoms had shewn a marked and comparatively sudden aggravation. Arguing from the success attending this operation in other cases, it is fair to assume that, if pressure had been relieved before compression had become estabhshed, alleviation and in some cases cure might have been the result. When drainage by puncture has been attempted and failed to give relief, the subsequent progress of the case is uniformly towards a fatal issue. The symptoms are mainly respiratory with dyspnoea and rapid shallow breathing, the patient's hands meanwhile beating the air; or again Cheyne-Stokes breathing may make its appearance. In some cases the patient dies of true respiratory failure, the respiration iv] Acute Forms 47 ceasing suddenly, and the patient becoming cyanosed, while the heart continues beating long after respiration has ceased. The temperature may rise to 105 or more before death. The symptoms in the acute type of case, in which recovery takes place, as a rule resemble those of the fatal cases though in a some- what minor degree. In rare instances the onset presents a striking similarity to that of a fulminating case. An officer's servant was admitted to the First Eastern Hospital having been found unconscious in bed at 2 a.m. He had been at his duties the night before, and had not complained of ill health. On admission, he was profoundly comatose, with twitching of the limbs, nystagmus, and retraction of the head. There was retention of urine and the patient was unable to swallow. The temperature was subnormal, and the pulse slow and intermittent. Lumbar pvincture was performed fourteen hours after onset, an ounce of purulent fluid containing meningococci being removed. The next day he was somewhat better; another ounce of purulent fluid was removed by lumbar pimcture. On the third day he was able to swallow ; the theca was again tapped, an ounce of purulent fluid being removed. From this date he made an uninterrupted recovery, being discharged on the eighteenth day. A macular reddish purple rash made its appearance on the fourth day, distributed over the abdomen, fore-- arms and legs. With the exception of the absence of dyspnoea and a purpuric rash, the earlier clinical features in this case bore a close resemblance to those observed in the fulminating type of the disease. The initial symptoms in this case are, however, quite exceptional: as a rule the march of the disease is slower and milder in character. The onset is marked by a sudden feehug of indisposition, the patient often being able to determine precisely the place and hour where he first experienced it. According to some authors, the onset may have been preceded by coryza or a sore throat; but in our experience such immediate prodromal symptoms were conspicuously absent. This feeling of indisposition is accompanied by complete anorexia, and is followed in two or three hours' time by shivering which usually takes the form of a definite rigor. The temperature rises rapidly to 102-103; the pulse is somewhat quickened, the respirations are only very slightly accelerated. Even before the initial rigor headache begins and gradually increases in intensity, usually accompanied by vomiting within the first twenty-four hours. Delirium may be present during the first day, but usually appears later. After this sudden onset the second day may be charactei-ized by no marked accentuation of symptoms 48 Acute Forms [ch. or even by some amelioration, "the period of bailing symptoms" of the French authors. A careful survey of the signs and symptoms at this stage is of great importance, as it may enable treatment to be instituted at once. Kernig's sign is usually present, and careful examina- tion of the muscles of the neck may reveal some tenderness and stiffness, which is increased by manipulation. Pain in the back and legs is a common complaint, but the significance of this symptom is equivocal. In our experience lumbar puncture on the second day, when we were so fortunate as to have an opportunity of performing it, yielded a purulent fluid at high pressure. With the third day all the symptoms shew marked aggravation. Dehrium becomes more marked, and may be accompanied by violence rather than restlessness. The delirium may be of a very noisy character, the patient disturbing the whole ward with his shouts and cries. Towards the end of the third day dehrium may merge somewhat abruptly into coma with complete inabihty to swallow. Head retraction becomes more marked, retention of urine, if it has not occurred before, is now complete. The aspect of the patient at this stage may appear wellnigh desperate. He lies pro- foundly comatose, his head retracted between his shoulders, mucus ratthng in his throat, the respiration hurried and irregular in rhythm, and swallowing an impossibility. And yet this perilous state, which would appear to signify a condition of profound toxaemia, is in fact largely the expression of increased cerebro-spinal pressure. If the theca is tapped and exit given to the excess of fluid early and frequently enough, such an apparently hopeless case may be led to a complete and early recovery. The cerebro-spinal fluid in these cases is at very high pressure, from two to three oimces being easily run off before the fluid assumes its normal rate of flow. The fluid is purulent and may contain flakes or clots of pus. On the fourth day herpes begins to make its appearance, usually on the lips or heUces of the ears. This eruption occurred on about one-third of our cases. At about the same date a macular reddish purple rash appears on the abdomen, the thighs, extensor surfaces of the forearms and legs, the backs of the hands and dorsal surfaces of the feet. The older physicians regarded the appearance of this rash, in distinction to the petechial form, as a favourable prognostic. Our own experience leads to the conclusion that a rash appearing on the fourth or fifth day occurs in cases which either recover or lapse into a chronic hydrocephahc condition, but in which the disease is not immediately fatal. The course towards recovery of these profoundly comatose cases is in some' instances iv] Acute Forms 49 almost as rapid as the onset of coma is sudden. The profound coma may continue for about two days, at the end of that time the patient begins to swallow, the sphincters resume their functions, and a glimmer of consciousness is discernible. If lumbar puncture is persevered in, recovery may be very rapid and \\ithout relapse or sequela. On the other hand, although consciousness may return, headache and intermittent fever may continue for weeks before complete recovery takes place, that is to say, the disease passes into a sub-acute stage. A rapid exacerbation of symptoms on the third or fourth day is in these cases by no means the rule. In many delirium does not pass into coma, though the fever remains high, the headache is intense, and retraction marked ; the patient can swallow and retention of urine passes off. With regular drainage the acute symptoms disappear in a week or ten days, though irregular attacks of fever, with increased headache and sometimes vomiting, may occur from time to time for weeks. These slight relapses are usually cut short by lumbar puncture. Should this fail, the intrathecal injection either of the patient's own serum, or of an antimeningococcal serum, may cut short these exacer- bations. A practical point of some importance is the variation in the amount of head retraction as recovery progresses. This symptom may entirely disappear and then after an interval again become marked. In our experience, if the theca is tapped under these conditions, not only does the fluid run at considerable pressure, but retraction ceases. This symptom is a definite index of raised cerebro-spinal pressure, and a clear indication for interference. At any time during an epidemic, but notably towards its decline, a certain number of mild or abortive cases are met with. Such cases usually begin with a rigor, accompanied by headache and followed by vomiting. There is often retention of urine for a day or so ; head retraction is not marked, though tenderness and stiffness of the neck muscles can generally be discovered on careful examination. Delirium is rarely present, a rash or herpes is uncommon ; Kernig's sign, however, is always present. If lumbar puncture is performed, it yields fluid at considerable pressure containing pus cells. Recovery is usually rapid. Films or cultures may or may not yield the meningococcus, but seeing that infection by the meningococcus is, as far as our present knowledge goes, the only non-fatal form of purulent meningitis, it is fair to assume that these are abortive forms of the disease. That the meningococcus has in some cases been recovered from the throat though not from the cerebro-spinal fluid, adds weight to this supposition. F. & o 4 CHAPTER V SUB-ACUTE AND CHRONIC CASES Four tyjyes of case. The suppurative type, absence of excess of cerebrospinal ft.uid. The recrudescent type, irregular crises. Relapsing cases, rarity of true relapse. Hydrocephalus principal danger in chronic cases, adynamic state. Importance of repeated puncture. Posterior basic meningitis, identity with cerebrospinal fever. The acute cases so far considered run a course in wiiicli the patient either dies during the first week, or is on the way towards recovery within about a fortnight. In a considerable number of cases, however, after slight general improvement, fresh symptoms may arise which protract the course of the disease and may leave the ultimate issue long in doubt. The diverse types of cases, which tend to run a longer and more complex course, may be divided into the following groups : 1. Suppurative. 2. Recrudescent. 3. Relapsing. 4. Hydrocephalic. The type of case, to which it is proposed to apply the name suppurative, is characterized by the fact that the cerebro-spinal fluid instead of becoming clearer becomes thicker and more purulent day by day. The onset and early days present no striking difference from the ordinary acute cases. The subsequent course, however, presents very striking points of difference, which are illustrated by the following cases. A patient was admitted with delirium and head retraction. Lumbar puncture on the third day yielded markedly purulent fluid. Considerable relief of symptoms followed the operation, but the succeeding punctures, instead of shewing any diminution in the amount of pus, indicated an increase. The patient died on the twenty-second day of his illness, having been for a number of days in an adynamic state with variations between complete consciousness and hebetude. Lumbar CH. v] Sub-acute and Chronic Cases 51 puncture yielded purulent fluid at fair pressure and in considerable quantity until the fifteenth day, when only one drachm could be obtained. Subsequent punctures never yielded more than one or two drachms. Post-mortem the base of the brain and spinal cord (Plate X, fig. 2) were coated with thick inspissated pus ; there was no marked excess of fluid. In another case, lumbar puncture on the fourth day yielded markedly purulent fluid in fair quantity and at considerable pressure. The fluid in subsequent specimens shewed an increasing quantity of pus ; on the sixth day large clots of pus blocked the cannula. On the ninth day only half an ounce of purulent fluid could be obtained, the amount fell to two drachms on the fifteenth day. From this date until death, which occurred on the nineteenth day, only one or two drachms were yielded of comparatively clear fluid containing little pus. Con- siderable relief of symptoms followed the earlier pimctures, but as less and less fluid could be drained ofl^, the patient sank into an adynamic state, in which he died. Post-mortem the base of the brain was covered with thick pus (Plate VIII), which extended down the cord entirely covering it. The pus was so thick and adherent that it could not possibly have flowed through any cannula. There was no excess of cerebro-spinal fluid. The absence of excess of fluid in these cases, coupled with the fact that none could be obtained by lumbar puncture, affords a striking contrast to the excess which was found in all other post-mortems in our experience. The phenomena observed in these cases would indicate that there exists a type of case in which the salient feature is that the infection of the meninges manifests itself in the secretion of dense adherent pus. The earlier stages of the invasion are accompanied by the usual out-pouring of an excess of cerebro-spinal fluid, but as the secretion of pus becomes estabhshed, excess of cerebro-spinal fluid disappears. These cases do not die with signs of increased cerebro- spinal pressure, but sink into an adynamic state clinically bearing some likeness to that seen in obstructive suppression of urine. It would appear as though the entire secretory mechanism of the cerebro-spinal fluid were paralysed by the pyogenic process. A striking feature of these cases is that neither constant lumbar puncture, nor the intrathecal injection of anti-meningococcal serum, prevented either the secretion of increasingly dense pus or the steady progress of the disease. In discussing the gradual recovery of acute cases, attention was called to the fact that progress was often not a uniform advance, but was marked by crises, accompanied by cerebral symptoms, interrupting the apyrexial course of convalescence. In some cases, when the acute 4—2 52 Sub-acute and Chronic Cases [CH. symptoms have subsided, the temperature remains raised for a period of possibly some weeks. The course of the fever is attended by marked remissions. These may be of so regular a character as to simulate a tertian ague. By the older writers stress is laid on the difficulties which attend the diagnosis of cerebro-spinal fever from pernicious malaria. Accompanying this fever there is usually some headache and a certain amount of mental hebetude. Chart 4 in Chapter II well illustrates this type of fever. In this instance lumbar puncture was performed in the early stages, but subsequently discontinued; the patient made a good recovery. This persistent temperature would appear to indicate that the infective process in the meninges is still active. Support is given to this view by the fact that, in other cases with persistent temperature, lumbar puncture repeated daily for a few days brought the temperature permanently down to normal, and a rapid convalescence ensued. In other cases again the temperature may remain normal for a few days, and then a rise of temperature occurs accompanied by headache, vomiting and perhaps retraction of the neck. If lumbar puncture is performed, a fair quantity of fluid flows at considerable pressure, this fluid is clear and contains few cellular elements; the meningococcus can however often be cultivated, though with difficulty, its appearance and disappearance often coinciding with the variations in the clinical condition. The accompanying chart (Chart 5) shews these variations breaking in upon the steady progress of convalescence. These slight crises are obviously due to a rise in cerebro-spinal pressure, and may be regarded as evidence of a renewal of bacterial activity. The practical point is that, when such crises arise, they form a definite indication for lumbar puncture. In our experience, not only was an increase of cerebro-spinal pressure always found, but the relief of this condition secured either a period of freedom from fever and cerebral symptoms or permanent cure. Had drainage not been maintained, it is probable that a prolonged period of irregular fever, such as has been before alluded to, would have ensued. In some instances, in spite of drainage by lumbar puncture, these crises recur. In one case under our care the intrathecal injection of 5 c.c. of the patient's own serum entirely cut short fever and cerebral symptoms, and was followed by convalescence. In our experience these apyrexial periods have not exceeded six or seven days. Sophian records a period of ten days. The important point is that Kernig's sign is present throughout, and thus distinguishes a late recrudescence from a true relapse. V] Sub-acute and Chronic Cases 53 Authorities differ markedly as to the frequency of relapse in this disease. The fundamental cause of this discrepancy is the varying significance attached by different observers to the term relapse. Ker records relapses in 15-20 per cent, of his cases. Sophian, on the other hand, has met with a true relapse in under 5 per cent, of his cases only. This author further suggests that cases regarded as relapses may have been all along slightly hydrocephalic. A case under our own care strengthens this assumption.. A man who had passed through a com- paratively mild attack had been free from symptoms for ten days; Kernig's sign was however still present. He was allowed to get up. The next day he was seized with headache and vomiting ; a considerable quantity of cerebro-spinal fluid was withdrawn at high pressure. Chart 5 ... ... 7R 102 em ffi3 em S« W-2 .,0 .. mn' ... m-? !f> m.2 J ^ ■a.^ ,7-M 26 IM s.ro ,„■ 1 ,»■ 1 % ,„, :! \ ^ ...■ ;| K 1 ""' 1 1 : fi ,.!• 1 : t 1 ,=,■ ■\ ■% \ N .«• -i 1 / V / »_ "• \ \ \ / \ i / '^ rW ' V K? ■ 1 ■> -H _ ^ ^. -f ^ -A _ V ■^^ ^ S- r 7\ t ^ ^ Br '%S zi. 20 io- 22, 201,22 SrS^ %%"° ^92 2o' 0, m^7t 90 leo ^72 "^'Ic'so 20 2t W 2*1 22l 20 7a '^a? 7& Symptoms of hydrocephalus rapidly developed, the amount of fluid obtained from lumbar puncture gradually diminished, and he died with all the signs of cerebral compression four weeks afterwards. Post- mortem the third and fourth ventricles were found dilated. The upper dorsal region of the cord was covered with thick pus and adherent to the theca. On holding up the cord with the theca intact, bulging of fluid was obvious as far as the level at which this coating was present ; the theca was flaccid below. It is reasonable to suppose that in this case interference with the circulation of fluid had occurred owing to adhesions following upon the original purulent exudate. The increased movement involved in walking may have upset the balance of the circulation to such an extent as to lead to hydrocephalus. The patho- logical conditions found, coupled with the presence of Kernig's sign 54 Sub-acute and Chronic Cases [ch. throughout, suggest that this case should be recorded as a recrudescence rather than a true relapse. As has been shewn in discussing recrudescence, fever and symptoms may be absent for as long as ten days, and yet the meningococcus be recovered in the cerebro-spinal fluid at the end of that time. Kernig's sign is as a rule a reliable guide as to the persistence of infection of the meninges. In one of our cases, which was still febrile, it was unobtainable for a few days, and then reappeared. The absence of Kernig's sign, coupled wiih an apyrexial state of more than ten days duration, would be necessary to distinguish a genuine relapse from a recrudescence. That genuine relapses occur is beyond question, but their frequency is doubtful. Lieutenant Colonel Adami informs us of the case of a private soldier in the Canadian contingent who was taken ill while crossing the Atlantic. When recovered, he went on furlough to his friends and there died suddenly from the after effects of cerebro-spinal fever long weeks after the primary attack. The possible explanation of such cases will be referred to in discussing hydrocephalus. In the preceding chapters it has been shewn that death may take place with starthng suddenness at the very onset, or the course of the disease may be uniformly downwards untilthe fatal event is reached at the end of the first five days. Where diffuse suppuration occurs, the case may be prolonged until the third or fourth week. Beyond this date death, when it occurs, is due to one cause and one cause alone — the development of hydrocephalus. Cases of chronic meningitis in our experience are not only similar in their cUnical features, but the anatomical conditions are also in the main identical. The development . of hydrocephalus is the comphcation most to be feared after the first week of illness. Extreme vigilance is needful to recognize the earlier symptoms, as a guide to prompt and methodical treatment. It is of the greatest importance to recognize at what an early stage dilatation of the ventricles can take place. A case under our care died suddenly from an intercurrent abdominal haemorrhage on the tenth day. The case was of moderate severity and appeared to be improving at the time of death. All the ventricles of the brain were found markedly dilated, as is shewn in Plate IX, fig. 2 which was drawn at the post-mortem. The amount of pus was small and mostly situated at the base of the brain. A considerable quantity was however present in the region of the cisterna magna ; and the cerebellum was adherent to the roof of the fourth ventricle. It is doubtful whether occlusion can become complete at so early a stage ; in the case described v] Suh-acute and Chronic Cases 56 an oimce and a half of fluid had been withdrawn by lumbar puncture sixteen hours before death. So large an amount of fluid must partly have been derived from the ventricles themselves. The onset of hydrocephalus is insidious, the distinguishing symptoms emerging but slowly from the general aspect of the case. At the latter part of the first week, although the more acute symptoms may have abated and the patient is not in obvious danger, the headache increases in severity. Dehrium may persist and is usually noisy in character, a constant complaint of headache dominating all other symptoms. If the theca is tapped at this stage, a large quantity of fluid escapes at very high pressure. This operation aft'ords marked reUef to the symptoms, the patient often passing straight from the anaesthetic into several hours of C[met slumber. Generally within twenty-four hours the headache returns with equal severity, and lumbar puncture yields fluid at equally high pressure. The temperature remains at a moderate height, 100-101 with irregular remissions. A rigor may occur at this stage, and its appearance is markedly suggestive of the presence of hydrocephalus. The pulse is of moderate frequency and of good tension. Retention of urine may be present, but as a rule at this stage the sphincters are unafl'ected. These symptoms may continue with slight daily variations through the second week. In a considerable proportion of cases a sudden and striking change makes its appearance at the latter part of the second week. This change may be ushered in by a rigor, in itself a suggestive symptom. Following the rigor or without this warning, the patient lapses comparatively suddenly into an adynamic state. This condition is characterized by profuse sweating, a feeble running pulse and incontinence both of urine and faeces. All complaints of headache cease and low muttering delirium, merging into unconsciousness, replaces the previous monotonous cries of suffering. The significance of this phase and its prompt recognition are of supreme importance. In our experience this crisis has always heralded a long and anxious struggle, which in fatal cases has been attended by pathological evidence of well-marked hydrocephalus. A source of error to be avoided lies in the fact that, where lumbar puncture has been frequently practised, this adynamic condition is apt to be attributed to excessive drainage of the sub-arachnoid space. On this supposition the wiser course may appear to be abstention from active interference, and a recourse to purely stimulating measures. As a matter of fact, the truth lies far otherwise; if lumbar puncture be performed at this stage, a considerable quantity of fluid is yielded at high pressure. The 56 Sub-acute and Chronic Cases [ch. crisis is an index, not of exhaustion but of pressure affecting the medulla. Further, the relief of pressure is attended with improvement, possibly slight, but always obvious. These facts warrant a perseverance in repeated lumbar puncture. In spite of the apparently desperate condition of the patient, the operation has in our hands been entirely free from danger. The subsequent course reproduces the classical picture of chronic meningitis. The body wastes with extreme rapidity ; vomiting occurs, but is not a sufficiently marked symptom to account for the rapid emaciation, which is presumably trophic in character. Carphology and subsultus tendinum are marked symptoms, and any movement is attended by tremors. In addition to head retraction, rigidity of other muscles rapidly makes its appearance. The elbows and knees become increasingly rigidly flexed, so that any movement is attended with considerable pain. The mental condition is one of apathy, varied by spells of quiet muttering delirium. The mask-like face of the patient reveals no consciousness of persons and events around him, though the sight of food or drink sometimes ehcits a gleam of recognition. In this connection great stress must be laid on the importance of feeding these patients. With regard to food they behave very much like some forms of imbecile, at times rolhng their food in their mouths without swallowing, or even spitting it out. It may thus appear at first sight that they are unable to swallow ; the exercise of patience on the part of a nurse, to whom they are accustomed, generally results in their taking a full meal. The condition of the optic discs was repeatedly observed in hydrocephalic cases; beyond marked fullness of the veins there were no pathological changes. In cases which recovered, the ophthalmoscopical appearance was normal, and vision was unimpaired. Direct evidence of hydrocephalus may some- times be supplied by the presence of MacEwen's sign. Sir William MacEwen has called attention to a change in the note elicited on per- cussing the skull which occurs when there is excess of fluid within the ventricles. The normal note yielded on percussion of the skull of the adult is high-pitched, in technical terms a pure osteal note. When the ventricles are distended, percussion about the pterion yields a note of a more resonant quality. A further point is that the area of resonance can be made to shift by altering the position of the patient's head. If the patient hangs his head to one side, the greatest resonance is over the lower parietal bone. On reversing the position of the head, the area of resonance is now found over the opposite parietal. This sign is more easily elicited in children than in adults ; its presence may v] Sub-acute and Chronic Cases 57 give confirmation to the evidence of liydroceplialus supplied by other symptoms. In some cases a sudden alteration in the lumbar puncture fluid takes place which is of very grave significance. Lumbar puncture yields a progressively diminishing amount of flmd. Finally a point is reached when only a drachm or two of perfectly clear fluid can be obtained. Pimcture as high as the last dorsal vertebra yields no better result, and should be avoided, as in our experience it has given rise to transient though alarming reflex phenomena. In fatal cases this con- dition persists until the end; the emaciation becomes extreme, the pulse feebler, until the supervention of Cheyne-Stokes breathing or sudden respiratory failure brings about the fatal issue. Post-mortem a complete obstruction in the sub-arachnoid space explains the condition. Another not imcommon cause of death is the invasion of the stagnant cerebro-spinal fluid by some other organism, such as the pneumococcus. "When, however, the obstruction is not complete, and the cerebro-spinal fluid stiU flows in fair quantity on puncturing the theca, improvement is slowly manifested, and continues till complete recovery is reached. The consciousness slowly returns, the sphincters regain their tone, rigidity disappears, and the patient rapidly gains flesh. Arguing from the close similarity between the symptoms of fatal cases and some who recover, it may fairly be assimied that the latter were cases of hydrocephalus in which there was interference with the circulation of the -cerebro-spinal fluid, stopping short of complete occlusion. It may also reasonably be supposed that such occlusion may exist in a minor degree without causing the complete chnical picture of hydrocephalus. CHnically this c^uestion can be answered in the affirmative. A definite group of cases present the early symptoms without reaching the extreme degree. After the subsidence of the early acute symptoms, the patients complain of agonizing and continuous headache. This headache is at once removed by lumbar pimcture, when fluid runs in large quantity at high pressure. AVithin twenty- four hours the headache may be as bad as ever, and again lumbar puncture aSords fresh relief. Such a condition may go on for days, and then gradually lessen. In some cases these headaches cease abruptly, and thenceforward the patient is entirely free from pain. Adopting the reasonable assumption that this headache is an indication of increased pressure in the cerebro-spinal fluid, its cessation must imply that an increase in pressure suddenly ceases to be formed. It can hardly be supposed that this is due to a sudden diminution of secretory 58 Sub-acute and Chronic Cases [ch. activity ; the conclusion is much more probable that the normal channels of drainage become adequately re-established. Such a sudden re- establishment is quite conceivable, for persistent puncture may gradually lessen the maximum tension below a certain critical point, at which the normal drainage is able to take place. Some evidence in this direction has been obtained, as a progressive diminution in the amount of fluid withdrawn has preceded the clinical crisis of sudden loss of headache. As all such cases in our practice were drained daily if necessary, the question as to whether they would have developed well-marked hydrocephalus cannot be answered. When recovery takes place, it is usually complete. In our experience any signs of mental enfeeblement were entirely absent. When the long period of compression and unconsciousness is considered, such complete recovery is a matter for some astonishment. Physically hydrocephalus leaves no sequelae ; the heart is miaffected and a local palsy is a very rare event. Stiffness and pain in the back may persist for a long time : several of our patients were unable to march with a pack for months. Late in the epidemic of 1915 a case was brought into our ward suffering from hydrocephalus. ' There was a history, dating back some weeks, of an acute attack of fever attended with headache and vomiting. On admission there was occasionally a day or two of severe headache, which passed off; the temperature was normal, the cerebro-spinal fluid was sterile. Death took place somewhat suddenly from respiratory failure. Post-mortem the ventricles were found dilated with sterile fluid and there were adhesions about the roof of the fourth ventricle, which occluded the foramen of Majendie. The supposition may be hazarded that this condition was the result of a past mild attack of cerebro-spinal fever. We have been informed by Major Burton Fanning of a case very similar to this, in which the acute attack had taken place some three months before. The patient had passed through an attack of cerebro- spinal fever in France, and been invalided home. While on leave he had begun to complain of headache for which he was admitted to hospital, though he was sufficiently well to be up during the daytime. Death took place during sleep. At the post-mortem well marked hydro- cephalus was found involving the third and lateral ventricles; the iter was completely blocked. A similar condition would account for some of the so-called relapsing cases, where death takes place at some con- siderable period after the primary attack, from which the patient was supposed to be either convalescent or cured. It is important to realize that a case may first come under observation when definitely suffering v] Sub-acute and Chronic Cases 59 from hydrocephalus, the preliminary acute attack having been regarded as influenza or a mild attack of pneumonia. The signs of hydro- cephalus may not be nearly so severe as in the more typical cases described above. The mental quahties may be merely dulled, and these with the attendant headache may shew a definite alternation of good and bad days. Such an alternation of symptoms has already been referred to in connection with fever, but in these cases the variations may occur without any rise of temperature. Gee and Barlow in 1878 published a paper in the St Bartholomew's Hospital Reports entitled, "On Cervical Opisthotonos in Infants." In this, attention was called to a previously undescribed condition, occurring in infants, characterized by initial fever with vomiting, and followed on the third or fourth day by retraction of the head. A large proportion of the cases ran a chronic course, characterized by head retraction, opisthotonos, tonic spasms of the hmbs and wasting. Accumulated pathological evidence shewed that these symptoms were always associated with either purulent meningitis about the base of the brain, or inflammatory thickening in the region of the cerebellum and medulla, notably near the cisterna magna. That is a posterior basic meningitis. The chronic form of the disease was found to be marked by hydrocephalus, due apparently to the occlusion of the foramen of Majendie and the fora- mina of Luschka. Carr in 1897 suggested the possibiKty that compression by inflammatory exudation might cause thrombosis of the venae Galeni, and thus produce a passive hyperaemia of the choroid plexuses. All the earher cases observed were of a sporadic character. In 1898 Still isolated a diplo-coccus from the cerebro-spinal fluid identical in its main features with the meningococcus of Weichselbaum. Subsequent researches have estabHshed the id-entity of the causative organism of posterior basic meningitis with Weichselbaum's meningococcus. The disease has occasionally occurred in small epidemics, and has shewn a seasonal prevalence identical with that of cerebro-spinal fever. Posterior basic meningitis may be regarded as cerebro-spinal fever with certain clinical differences due to the anatomical development of childhood. Our own experience of cerebro-spinal fever having been almost entirely acquired amongst soldiers, we do not lay claim to experience other than that of ordinary physicians in discussing this disease. The disease usually occurs in children from six months to two years of age, though older children may be affected. The onset is sudden, often accompanied by a convulsion, generally by vomiting, and followed by a rapid rise of temperature. Persistent screaming may be a marked symptom at the 60 Suh-acute and Chronic Cases [ch. onset. Head retraction occurs early, appearing on the first day in half Lees and Barlow's cases. A certain number of those attacked die in the early stage, more, probably, than are recognized, owing to death , being attributed to convulsions. In other cases head retraction increases, and tonic spasm of other muscles rapidly follows, the arms and legs are rigidly flexed and opisthotoiaos develops. The position of the limbs varies in different cases, the commonest is rigid flexion of both arms and legs, though in some cases there may be rigid extension of all four limbs. Vomiting as a symptom rarely disappears entirely, and may be distressing. The respiration is generally irregular and is frequently of the Biot or cerebral type, with irregular periods of apnoea and marked sighing. The unmistakeable hydrocephalic cry is often present at this stage, and rapid wasting accompanies these symptoms. Kernig's sign is a physiological attribute up to the age of two years, consequently its presence is of no clinical value. The patency of the fontanelles also prevents the full development of MacEwen's sign. On the other hand, the marked bulging which is always present supphes even more convincing evidence of the presence of hydrocephalus. The chnical picture in many respects closely resembles the hydro- cephalic type, as seen in adults. The anatomical condition of the infant's bony system, however, introduces a factor which essentially modifies the clinical aspect of the disease. Owing to the yielding nature of the cranial bones and the patency of the fontanelles, increased cerebral pressure does not exercise all its force upon the nervous elements, but in addition produces an outward thrust upon the skull cap itself. The results of this centrifugal pressure are twofold. In the first place, the nervous structures are to some extent spared, and the case tends to run a more chronic course than that seen in the adult. In the second place, the parietal bones are splayed outwards and the fontanelles bulge. Pressure on the orbital plate tends to turn the eyes downwards, until finally the classical appearance of external hydrocephalus is com- plete. Further, the slower compression, to which the nervous elements are exposed, gives rise to the occurrence of symptoms which are but rarely observed in the more rapid course of the disease in the adult. Of these the most notable is the common occurrence of bhndness, as compared with its rarity in older subjects. Amaurosis would appear to be of central origin, since optic neuritis with atrophy is extremely rare. The optic lobes, situated as they are immediately beneath the already ossified occipital bone, are necessarily exposed to greater pressure than the motor areas. Pressure thus exerted may be the cause of the bhndness. v] Sub-acute and Chronic Cases 61 the common occurrence of occipital tenderness tends to strengthen this supposition. Deafness by contrast is less common in posterior basic meningitis than in the epidemic form. A further result of the prolonged compression of the brain is the relative frequency of subse- quent mental impairment compared to its rarity as a sequel of cerebro- spinal fever. The chronic character of the disease is shewn by Lees and Barlow's statistics, which give an average duration of 7-8 weeks for 30 cases. Individual cases may run an even longer course, some lasting as long as nine months. The mortality is very high, probably about 80 per cent. Death usually occurs from exhaustion. Here, as in all wasting diseases, the body is peculiarly liable to a terminal bacterial infection, which rapidly becomes generalized. The stagnant cerebro-spinal fluid affords a peculiarly favourable nidus for such an invasion. Infection of the cerebro-spinal fluid at this stage is rapidly fatal. The infective agents are generally the pneumococcus or the bacillus coli. With regard to treatment, various surgical procedures have been devised for securing drainage of the cerebro-spinal fluid. Tapping the ventricles, trephining the occipital bone, and various other methods of drainage have all been practised. No method has hitherto met with sufficiently marked success to secure its general adoption. The diverse possible situations of the seat of obstruction may render an operation planned for a special contingency only partially successful in securing drainage. As in all cases of cerebro-spinal fever, the patient so often comes under observation too late ; the obstruction to free circulation of fluid is already formed. Should the disease be met with sufficiently early, treatment by daily lumbar puncture would hold out considerable hope of success. CHAPTER VI COURSE AND PROGNOSIS Incubation. Course. First day, second day, stage of baffling symptoms, third day, death befwe sixth day in acute fatal type, course of recovery, termination by crisis and lysis, chronic intermittent cases. Immediate prognosis based on signs and symptoms, date of treatment, age of patient, stage of epidemic. Remote prognosis. Contrast of sequelae in earlier and later epidemics. The period of incubation in cerebro-spinal fever has not so far been determined with certainty, and rests mainly on indirect evidence. As case to case infection is very difficult of identification, evidence derived from this source is only occasionally available. In our experience the facts, which throw most light on the probable period of incubation, are derived from instances in which a case occurred amongst troops, hitherto free, in the person of a man just returned from leave. Three of our cases occurred in men returned from leave, and were the first instances of the disease met with in their station. In one case at Bishop's Stortford, a man returned from four days' leave and developed the disease on the day of his return. At Houghton Regis again a man returned from four days' leave and developed the disease in a fulminating form the day after his return. In another case occurring at Watford, the disease developed the day after the man's return from five days' leave spent in London, where cerebro-spinal fever was then prevalent. These three cases were the first to occur in their respective stations, and it may be assumed that the disease was contracted while the man was on leave. On this assumption the period of incubation cannot, at the longest, have been more than four days in one case, and five days in the other two. Two other cases developed the disease on return from leave, the actual onset occurring only three days after the commencement of leave. As other cases had, however, occurred previously in the station, the evidence is thus less definite than in the former cases. The evidence furnished by these five cases would put the period of incubation at from three to five days. Turning CH. vi] Course and Prognosis 63 to the case of men who contracted the disease while on leave, two cases occurred at Littleport in men who were on leave for three and four days from FeUxstowe and Bury respectively. The first of these two men to fall ill came from Bury, where the disease was not then prevalent, the first symptoms appearing on the third day of his leave. The second man came from Fehxstowe, where epidemic meningitis had plready appeared among the troops ; the evidence derived from his case is therefore equivocal. In the case of the first man, it may be remarked that he came from a station which was free from meningitis throughout the winter and spring, and that meningitis had already appeared in the neighbourhood of Littleport. A consideration of these facts warrants the assumption that this man contracted the disease at Littleport, in which case the period of incubation would be at the longest three days. In another instance, a man developed the disease fourteen days after going on leave, but as furlough was granted in order that he might visit a sick sister, it is possible that she may have been suffering from an unrecognized form of cerebro-spinal fever. This man moreover came from Bury, where, as has been stated above, the disease was not prevalent, into a district where it had already appeared. The evidence regarding the length of incubation in this case, therefore, runs counter to the assumption that the incubation period was as long as fourteen days. Such evidence as our cases are capable of affording would lead to the conclusion that the period of incubation has a maximum Hmit of not more than five days. Evidence from other sources is furnished by a singularly apposite quotation of Netter's from Richter. Regina B. passed the entire day of October the 17th with a family where there were two children suffering from meningitis. She returned to her uncle's house, where she first shewed symptoms of cerebro-spinal fever on the 21st of October. On the 8th of November, when fully con- valescent, she received the visit of a young man, who in his turn developed the disease on the 10th of November. This young man had a mild attack, and was able to return to his office on the 15th of November. On the 19th of November his neighbour at the same desk developed the disease. This remarkable chain of infection would point to an incubation period of from two to four days. Sophian quotes two cases which are sufficiently unequivocal to have a distinct bearing on the question. In the year 1911 cerebro-spinal fever was not epidemic in New York. There was, however, at that date an extensive epidemic in Greece, and Greek immigrants, some of whom were suffering from 'the disease, were arriving in the Port of New York. A doctor, who 64 Course and Prognosis [ch. as far as was known had not been exposed to infection from meningitis, performed a post-mortem examination on a case which had actually died on the steamer. At the end of 24 hours he developed a mahgnant form of the disease. The second case was that of another doctor who treated a Greek immigrant for a febrile condition other than meningitis ; five days afterwards he developed the disease. Swabs taken from the throat of the patient proved him to be a carrier. A consideration of the evidence, furnished by the cases which have been set forth, tends to shew that the period of incubation varies between three and five days. The former Hmit would appear to be the more usual period, while in the malignant forms this may be still further shortened. The course of epidemic meningitis has already been to some extent sketched in deahng with the various phases of the disease. Certain features, which attend the progress of the disease, may be considered from a more general standpoint. The onset is as a rule sudden, and in the majority of cases is marked even more definitely by a rigor. Following the rigor, the first day is accompanied by the onset of fever and the rapid development of the earher cerebral symptoms, headache and vomiting. The course of the second day is frequently marked not only by no aggravation of symptoms, but even by a partial improvement in the general condition of the patient. This apparent pause in the march of the disease has been described by Netter as the "periode des symptomes frustes," "the stage of baffling symptoms." The recogni- tion of this period of seeming improvement is a matter of great practical importance. A considerable number of cases are never seen on the first day, and the apparent improvement on the second may either induce a sense of false security, or appear to warrant an expectant attitude. As a consequence, time may be allowed to go by without either a definite diagnosis being arrived at, or appropriate treatment begun. A careful and judicious examination at this stage will probably discover the presence of Kernig's sign, and some stifliness and tenderness of the muscles of the neck, thiis revealing the true nature of the malady masked by the apparent improvement. The presence of these signs would justify lumbar puncture. The character of the fluid yielded by this operation, and the pressure at which it flows, would probably confirm any suspicion which may have been entertained as to the nature of the case. When the experience of all those who have been concerned with the treatment of the disease in the latter epidemics is reviewed, a remarkable unanimity of opinion is found to exist as to the paramount vi] Course and Prognosis 65 importance of early treatment. Flexner's statistics furnish a striking proof of the marked value of treatment begun at the earliest possible moment. In our own experience, whenever we were so fortunate as to have the opportunity of beginning treatment at an early stage, the difference in results was very striking when compared with those obtained by interference at a later period. The importance of the recognition of the false improvement on the second day hes not only in the intrinsic value of early diagnosis and treatment, but also in that this apparent calm is the herald of a fresh exacerbation. With the third day, in spite of any apparent previous improvement, all the existing symptoms are aggravated, and fresh ones now make their appearance. Dehrium accompanies the existing headache, and in turn may rapidly give place to coma. Eetraction of the head and muscular rigidity in other parts mark the more remote effects of increased intra-cranial pressure. By this time, therefore, the classical symptoms of the disease have become manifest, and the diagnosis placed beyond doubt, often, however, after the unrecoverable chance of early treatment has been let shp. From the third day, in fatal cases, the symptoms steadily and rapidly increase in gravity until death. In commenting on the cases which have been grouped together under the name acute fatal type, attention was called to the one feature common to all, that they shewed no response whatever to treatment, their course being uniformly downwards. As a measure of the relentless march of the disease in cases of this nature, it may be noted that death practically always occurs within the first five days. Of fourteen deaths which occurred in the cases under our care, no less than nine occurred during the first five days of the illness ; in contrast, the next shortest period in which death occurred was on the nineteenth day. After a long interval, in which no cases occurred in the district under our charge, an acute case came under our notice in December, 1915, which again illustrated the two facts just insisted upon, an illusory improvement on the second day, and a fatal termination before the end of the fifth day. It would appear as though the acute fatal type was more than a mere aspect of the disease, but rather represented the power of endurance of the body in cases in which protective reactions were apparently unable to develop. In this connection it seems reasonable to suppose that, with an infection of such virulence, a period of about five days marks the longest time in which the primary on- slaught of the disease is hkely to be fatal. Should the patient survive the fifth day, death, if it occurs, will more probably be brought about F. &G. 5 66 Coiirse and Prognosis [cH. by some other condition such as hydrocephalus or the supervention of diiiuse suppuration. In cases which pass the fifth day and then recover, the symptoms may persist through the sixth or seventh day with apparently unabated severity. More usually, however, on one of these days or at the longest before the eighth day has passed, signs of improve- ment begin to manifest themselves. The abatement of symptoms, when once begun, may be very rapid, and convalescence is soon estabhshed. Such a sudden improvement may be accompanied by a fall of temperature to the normal, at which level it is maintained. Flexner and other authors speak of this sudden and permanent ameHoration of symptoms as termination by crisis, and contrast its features with the more gradual and irregular improvement usually observed, which they call termina- tion by lysis. This sudden fall of temperature and abatement of symptoms undoubtedly bears a superficial resemblance to the true crisis, as seen in pneumonia and typhus. It may be doubted, on the other hand, whether this analogy can be upheld, since an almost equally sudden abatement of symptoms may be observed in cases of chronic meningitis from the twentieth to the thirtieth day. Now a crisis in the strict sense of the term involves some sudden change in the mutual relations of the fluids of the body and the products of infection. That such an essentially vital change could take place at such widely different stages of any disease is contrary to chnical experience. The crisis in pneumonia may take place on the fifth day and that of typhus on the fourteenth, but the crisis of each disease conforms with a considerable degree of punctuahty to the accustomed course of one or other disease. It would appear more probable that this sudden amelioration is due rather to the opening of channels of drainage from the sub-arachnoid space, than to any alteration in the mutual relations of the fluids of the body. Assuming the adequacy of such an explanation, the term crisis would appear to be a misnomer, in that it tends to suggest a vital process, when the cHnical symptoms are largely to be explained on physical grounds. When the dangers present up to the fifth day have passed, the ultimate outlook is by no means certain. Examination of the cerebro-spinal fluid may shew that, instead of becoming less purulent, the amount of pus steadily increases. Such a condition indicates that the case is passing into the suppurative stage, in which the course may be protracted till the fourth week, but almost invariably termin- ates fatally. In other cases excruciating headache may persist for many days, accompanied by great tension of the fluid as evidenced by lumbar puncture. Under such coiaditions hydrocephalus may vi] Course and Prognosis 67 become established in the second or third week, its onset usually being marked by a sudden lapse into an adynamic state. Or again the case may run a long course with irregular attacks of fever, accompanied by headache. Systematic investigation of the cerebro-spinal fluid during these exacerbations will frequently indicate an increase of bacterial activity coinciding with each aggravation of chnical symptoms. In chronic cases these exacerbations may appear in a remarkably regular manner, bad days, in which the symptoms are severe, alternating with good days when the patient appears practically convalescent. This alternation may be marked by a corresponding variation in tempera- ture, which is often so regular as to simulate a tertian ague (Chart 4, p. 17). Such chronic intermittent cases ultimately make a good re- covery, death from exhaustion, except in hydrocephahc cases, being a practically unknown event. The variations in the course of the disease, which have been just described, shew that prognosis is a matter of considerable difficulty. In no disease commonly seen within these islands can such dramatic changes be witnessed as in the diverse phases of cerebro-spinal fever. An apparently desperate case may make a rapid recovery, while one of milder onset runs a uniformly downward course terminating in death. Experience is rendered even more fallacious in that nothing is more bafiling than a forecast of the probable results of treatment. Such cHnical guides as we possess may be considered under the following heads: 1. The signs and symptoms of the patient. 2. The date at which treatment is begun. 3. The age of the patient. 4. The stage of the epidemic at which the patient is attacked. The method of onset, seen in fulminating cases, almost always portends a fatal result. As has been shewn before, sudden loss of consciousness as an initial symptom is not necessarily fatal. This exception is, however, so rare as to be neghgible. A purpuric rash appearing in the first 24 hours is of grave prognostic significance. A petechial rash appearing on the first or second day is equally un- favourable. The presence of extreme dyspnoea in a marked form is in our experience always a mortal symptom. Cyanosis is almost equally unfavourable. Of physical changes restlessness is a more unfavourable prognostic than noisy dehrium or profound coma. The supervention of hydrocephalus, as evidenced by a sudden lapse into an adynamic state, is of grave but not fatal significance. High fever at the onset, an irregular pulse, marked retraction and carphology have not in our experience betokened a necessarily fatal issue. The appearance 5—2 68 Cotirse and Prognosis [ch. of the cerebro-spinal fluid at the onset affords no criterion of the gravity of the disease. A fluid clear at one puncture may be intensely purulent at the succeeding one. Bacteriologically the presence of extra -cellular meningococci marks the grave but not necessarily fatal character of the case. The older physicians laid considerable stress on the presence of herpes and of a macular rash, appearing late, as signs of favourable prognostic import. The pith of this observation probably lies in the fact that both these symptoms are late in appearance, from the third to the sixth day, a period at which the immediate issue of the case is already largely decided. In our experience the presence of herpes is a fallacious guide, some of our most fatal cases presented a marked herpetic eruption. With regard to a macular rash, in our experience no case which presented this rash was immediately fatal, although some died subsequently of hydrocephalus. The date at which treatment is begun is a factor of great importance in prognosis. When drainage can be established on the first or second day, in other than fulminating cases the prognosis is good. On the other hand should treatment not be undertaken until the fourth or fifth day or later, there is always the possibihty that the power of reaction of the patient may have become exhausted, or that an exudation has already formed which may lead to hydrocephalus. The age of the patient forms some basis for a forecast, in that the mortaUty rate of an epidemic follows a more or less defined curve in relation to the age at which the cases are attacked. The greatest mortaUty occurs in infants imder two years of age ; after two years of age, it begins to dechne imtil about the fifteenth year. Netter regards the death rate as lowest from the seventh to the fifteenth year. After the fifteenth year the rate increases somewhat, to fall sUghtly in the decade from twenty to thirty. After thirty it rises abruptly and con- tinues to rise with each decade of fife. Our own experience, which included all the cases drawn from troops quartered in the counties of Cambridge and the Isle of Ely, Huntingdon, Bedford, Northampton, Hertford and part of Buckingham, yields the following results. Cases occurring in men between 17 and 22 were 23 in number, of whom 9 died, a mortahty rate of 40 per cent. Between the ages of 22 and 30, there were 13 cases, of whom 2 died, a mortahty rate of 15 per cent. Four cases occurred in men between 34 and 45, of whom 3 died, a mortahty rate of 75 per cent. From these figures it woidd appear that the chances of recovery materially increase when full maturity is reached. After the age of thirty, the chances of recovery markedly diminish. vi] Course and Prognosis 69 The prognostic value to be attached to the age of the patient is of subsidiary importance, but may serve to introduce an element of caution in giving a favourable or unfavourable opinion. The stage of the epidemic, at which the patient is attacked, may be taken into account in forming a forecast of the probable course of the disease. It is stated by Netter and others that there are more fulmin- ating and severe cases at the beginning of an epidemic, and that the later cases assume a mild or abortive type. That the final stage of an epidemic is marked by a mild type of the disease is incontestable. The period of maximum intensity as regards virulence of type is, however, not so definitely estabhshed. Our own experience does not bear out the view that the earlier cases present the most dangerous type. All the cases, forty-eight in number, occurring during the first six months of the year 1915 amongst troops quartered in the five and a half counties already mentioned, have been collected. This includes eight cases which were not treated by us. These cases with their relative mortality have been tabulated by months. The accompanying table shews the relative virulence of the epidemic in each month, as evidenced by percentage mortaUty. Deaths taking place before Percentage Month Cases Deaths the fifth day mortality January 4 February 12 5 4 41 March 15 7 4 47 April 9 7 5 77 May 4 1 1 25 June 4 1 25 From this table it wiU. be seen that the onset of the epidemic was marked by a series of mild cases. The virulence then steadily increased until April. The subsequent two months shew an abrupt dechne in the percentage of fatal cases. A further study of our records accentuates the culminating period of virulence and its abrupt dechne. The first 14 days of April yielded 8 cases with 7 deaths, a mortahty percentage of 87. In 5 cases death took place in imder 5 days. In the following 6 weeks there were 9 cases with 2 deaths, a mortahty per- centage of 22. One case died in under 5 days. These figures demon- strate the fact that the virulence of the epidemic steadily increased, until the acme was reached in April. From that time a very abrupt decline in mortahty took place. As further evidence of the mild character of the later cases in the epidemic, it may be noted that, in the four months subsequent to the 1st of July, three cases have been 70 Course and Prognosis [oh. admitted with hydrocephalus, from which they died. In these cases the primary stage of the disease had been so Uttle defined as to give rise to error in diagnosis. In so far as any aid to prognosis can be obtained from these figures, the conclusion would be that, until a marked dechne in virulence had been established, the later in the epidemic the individual was attacked, the greater the probable severity of the disease. As has frequently been insisted upon, the remote prognosis of cerebro-spinal fever is usually good. Allusion has already been made to the possibihty of imbecility following posterior basic meningitis in infants. In the adult it might be conjectured that a disease, the essential features of which are dependent on prolonged cerebral compression, could not fail to leave behind some impress on the mental condition of the patient. The further the subject is pursued, the more evident does the extreme rarity of mental enfeeblement as a sequela become. Netter, in a chapter of great hterary charm, entitled "L'Avenir du Meningitique " affirms his conviction that no such enfeeblement occurs. Our own experience entirely confirms this view, in none of our cases was there any enfeeblement of the mental powers when complete re- covery had taken place. Not only were the mental powers unaffected, but no change in the moral balance of the patients, as evidenced by waywardness or moroseness, was observed. In the Hitchin Home for soldiers convalescent from cerebro-spinal fever, out of thirty-two inmates drawn from all over the country, only one case shewed any signs of mental change. In this case there was complete loss of memory, but, as concomitant palsy of the right arm was present, the defect would appear to owe its origin to a locahzed cortical lesion, rather than to psychical degeneration. At a subsequent visit six months later his memory was almost completely restored, though some feebleness of the arm still remained. Headache may continue for some time when convalescence is well established and Kernig's sign is absent. In common with the majority of post-febrile nervous affections, this symptom entirely disappears within a few months. Deafness may disappear at the end of two or three months, but in a certain number of cases the patient remains totally and incurably deaf. In the extremely rare cases in which blindness results in adults, it is due to optic atrophy and is permanent and incurable. A locahzed palsy either of one of the cranial nerves or of a hmb may persist for some months after convalescence is estabhshed. If the case be followed up, the palsy will almost invariably be found to have disappeared. Restoration of function may not, however, be complete for many months. vi] Course and Prognosis 71 Other symptoms which persist for a long time are pains in the back and legs ; the pain and stiiiness of the back with its accompanying awkward gait may persist for many months. Some of our patients, who were far too good soldiers to be suspected of mahngering, were totally unable to march with a pack for three or four months after rejoining their regiments. In all cases this disabihty eventually disappears. Sequelae other than those pertaining to the nervous system are practically unknown. In contrast to other fevers, the heart muscle is entirely unaffected. Endocarditis has been described as a sequela, but its occurrence is infinitely rare. The kidneys are entirely unafEected, the transient febrile albuminuria completely disappearing. It must be remembered that the differentiation of the gonococcus and meningo- coccus is extremely difficult, therefore accounts of metastatic foci due to meningococcal infection must be received with caution. The comparative rarity of sequelae in the recent epidemics affords a curious contrast to their apparent frequency in those of the past. Through all the writings of the older physicians there runs the same note of warning, that many of the survivors would suffer some permanent infirmity. This conclusion was reached after experience of epidemics in which aduJts and children were alike stricken, and cannot have been prompted by observing cases of posterior basic meningitis alone. The explanation of this change of view would appear to be a twofold one. In the first place cases of the cerebral form of acute anterior poho- myehtis were probably not differentiated: in consequence subsequent palsies due to this disease were attributed to cerebro-spinal fever. In the second place the tension of the cerebro-spinal fluid was entirely unreheved by the older methods of treatment. Whatever method of treatment has been adopted in later years, the theca has usually been punctured. Consequently, in cases occurring in the latter epidemics, the nervous elements have not been exposed to the same prolonged pressure as was the case in earher outbreaks. The absence of chronic nervous sequelae in the latter epidemics, compared to their relative prevalence in past times, goes far to strengthen the view that their essential cause was prolonged pressure. Netter, Flexner and Sophian attribute apparent diminution in the frequency of sequelae and their lessened gravity to the employment of serum. That serum alone is the determining factor may be questioned, since our own cases also shewed a singular absence of sequelae. In the majority of these adequate drainage by lumbar puncture methodically repeated was the only method of treatment. CHAPTER VII TREATMENT Fatal nature of the disease. Early methods of treatment, their failure. Introduction of serum treatment, researches of Flexner and Jochmann, diminished mortality. Serum treatment in the epidemic of 1915, statistics of First Eastern General Hospital. Treatment by lumbar puncture alone. The dangers of serum treatment, the procedure to be adopted, dosage to be employed, indications for suspension of treatment. Method of simple lumbar puncture, its comparative safety, indications for the continuance of treatment, possible sequelae. Treatment by other methods, vaccines, soamin, hexamine. General treatment, nursing, food, drugs, operative treat- ment. The statistics of the earlier epidemics manifest the extremely fatal nature of cerebro-spinal fever. This mortality varied sensibly according to the nature of the epidemic, but even outbursts of a mild type stamp cerebro-spinal fever as one of the most fatal of all diseases. Methods of treatment innumerable succeeded one another, their adoption being largely influenced by the pathological views current at the time. The antiphlogistic method of treatment, in vogue at the date of the first recognition of the disease, remained in fashion to some extent till recent times. In a disease so obviously desperate, and in which the hope of arrest by natural means was so slight, it was held that none but active measures were likely to be of any avail. Consequently venesection from the arm or the jugular vein was practised in all cases. In addition leeches to the head, blisters to the scalp and neck, dry and wet cupping to the spine, were all used as auxiliary methods of treatment. iWercury was pushed to salivation either by the mouth or inunction. The administration of emetics completed the tale of active measures. In spite of these heroic methods the death rate of the disease remained as high as ever. As conceptions of treatment changed, the administration of drugs and soothing remedies succeeded the more violent procedures of a former generation. The apphcation of ice to the head, or Leiter's CH. vn] Treatment 73 cap, to allay cerebral inflammation, tlie administration of iodide of potassium to promote absorption, and the use of opium to relieve pain were extensively employed. The immersion of the patient two or three times a day in a warm bath undoubtedly conferred great relief to symptoms. With these milder methods of treatment, the patient's sufferings were doubtless lessened and his strength husbanded, but no appreciable effect was produced, upon the death rate. As an index of the apparent failure of treatment, the statistics of the epidemic of 1904-5 may serve as an illustration. It must be borne in mind that these statistics refer to a time when the causative organism of the disease had been isolated and great strides had been made in pathological knowledge. The figures for New York City, according to Heiman and Feldstein, were 4000 cases with 3429 deaths : a mortality of 86 per cent. The records of the children's hospital in Boston, where every case was bacteriologically confirmed, show, according to Dunn, a mortality varying from 70 per cent, in 1902, to 90 per cent, in 1907. In the Belfast epidemic during the eighteen months ending January 1908 there were 725 cases with 548 deaths: a death rate of 76 per cent. Ker, during the same epidemic in Edinburgh, had 108 cases with 87 deaths: a mortality percentage of 80. These statistics shew that, up to this point, scientific research had failed to secure any therapeutic method which was practically more successful than the antiphlogistic measures of our grandfathers. But the labour spent in years of pathological research was soon to bear fruit. In 1905 Flexner in America and Jochmann in Germany began a series of researches on the possibihty of producing a serum which would be bactericidal to the meningococcus. Experiments were first made on small animals in the laboratory. As a result of his investiga- tions Flexner produced a serum which rendered small animals immune to lethal doses of culture of the meningococcus. He next produced a serum from goats which, when injected intrathecally into monkeys, was protective to injections of live cultures of the meningococcus. A control animal which received no serum died. Jochmann also produced a serum which experimentally was demonstrated to possess bactericidal properties. Flexner, continuing his researches by means of injecting horses with both dead and live cultures, finally produced an anti-serum of demonstrable value. To Flexner must be assigned the credit of selecting the intrathecal method of adrm'nistering the serum in preference to its subcutaneous or intravenous injection. He con- cluded that by this means the direct action of the concentrated serum on LIBRARY CP THE COLUMBIA UNiyEi 90, 91, 142, 149, 153 206 Bihliograpliii and Index of Authors Page in Author Title of Reference Kefur- Page WEICHSELBAUM, A. '■ Zur Frage der Aetiologie unci Patho- genese der Epidemischen Genick- starre". . . ~; . . 162 Wien. Klin. Wooh. 1905 992 WEST, C. E. . "The bacteriology of chronic post- nasal catarrh" _. Proc. Roy. Soc. Med. Otological 133 section. Vol. iv. 1911 44 WESTENHOFFER, M. . " Pathologische Anatomic und Infek- tionsweg bei der Genickstarre " . 105 Berl. KUn. Woch. Bd xlu. 1905 737 "Ueber den gegenwartigen Stand 105 unserer Kenntniss von der iiber- tragbaren Genickstarre" Berl. Klin. Woch. Bd XLiu. 1906 1267 " Ueber die Praktische Bedeutung der 105 Rachenerkrankung bei der Genick- starre" Berl. KUn. Woch. Bd XLiv. 1907 1213 WILKINSON, Col. . " Discussion on Cerebro-Spinal Menin- gitis" Proc. Roy. Soc. Med. Vol. viii. 11 No. 5. 1915 81 WHITTLE, E. . . . "Varieties in the type of ordinary fever in Liverpool" 6 London Medical Gazette. 1847 807 WOLLSTEIN, M. "The Para-Meningococcus and its anti-serum" Journal of Experimental Medicine. 166, 167 Vol. XX. 1914 201 "Biological Relationships of Diplo- 167 cocous Intraoellularis and Gono- coccus" Journal of Experimental Medicine, Vol. IX. No. 5. 1907 1 WOOLLEY, G. N. . "On an epidemic of Cerebro-Spinal Meningitis at Bardney" 7 Lancet. Vol. ii. 1867 130 WYNTER, W. E. " Four oases of Tubercular Meningitis in which Paracentesis of the Theca VertebraHs was performed for the relief of fluid pressure " 30 Lancet. Vol. ii. 1891 981 GENERAL INDEX Abdominal reflexes, 23 Abortive oases, 49 Absence of pus in hydrocephalus, 102 Absorption of cerebro-spinal fluid, path of, 96 „ tests, 164 Acclimatization, importance of, in susceptibility, 127 Accumulative stage, 43, 117 Acute fatal tjrpe, 44 „ „ „ course of, 65 ., „ ,, morbid anatomy of, 98 „ forms, 41 „ ,, gradual recovery of, 51 „ type with recovery, 47 Adenoids as nidus for meningococcus, 122 Adhesions in cord, 53 „ in sub-arachnoid space, 109 Adynamic state, in hydrocephalus, 55, 67 „ „ in suppurative type, 50 „ ,, indication for puncture, 82 „ ,, value in prognosis, 67 Age, importance of, in infection, 127 ,, of patient, value in prognosis, 68 Agglutination reactions, 162 „ „ classification by, 147 ,, „ macroscopic method, 163 Agglutinative power of patients' serum, 78, 106 Agglutinins, specific, 164 Albenga, first epidemic period in, 4 Albumen, increase of, in cerebro-spinal fluid, 112 Alternation of good and bad days in hydrocephalus, 59, 67 Ambulatory cases, 43 Anaesthesia, daily, not harmful, 81 „ general for lumbar puncture, 30 „ „ „ serum injection, 79 local, 31 Anaphylactic symptoms, 80 Anatomy of membranes of brain, 92 „ „ of cord, 94 Ankle clonus, 23 Anorexia at onset of acute tjrpe, 47 Antiphlogistic treatment, 72 Apathy in hydrocephalus, 56 Aphonia, 26 Apnoea, in posterior basic meningitis, 60 Appetite, loss of, at onset, 13 Apyrexial periods, 16 ,, ,, in cases with gradual recovery, 52 Arthritis, morbid anatomy of, 104 ,, treatment of, 87 Arthropathies, 25 Aspect, in early stage, 18 Aspirin, for headache, 87 Attendants, risks to, 131 208 General Index Attitude of patient in early stages, 18 Auricular fibrillation, 27 Autolytic ferment, 150 Auto-sedimentation, 163 Babinski's plantar reflex, 23 Back, pain in, see Pain in back Bactericidal power of patient's serum, 107 Bacteriological characteristics of cerebro-spinal fluid an indication for puncture, 81, 82 Baflfling symptoms, period of, 48, 64 Barometer, changes in relation to disease, 129 Bath, treatment by warm, 73 Bedclothes, disinfection of, 85 Bed sores, prevention of, 85 Belfast epidemic, 9 Blot's breathing, in acute fatal type, 45 ,, ,, in posterior basic meningitis, 60 Bismuth, for vomiting, 87 Bladder, necessity for care of, 86 Blindness, in posterior basic meningitis, 60, 104 ,, as sequel in adults, 70 Blisters, in earUer methods of treatment, 72 Blood, meningococcus in, 104 ,. agar, best medium for meningococcus, 149 cultures, 105, 117 ,, pressure, changes during puncture, 34, 110 „ „ „ ,, serum injection, 77, 79, 110 Biain, anatomy of membranes of, 92 Brandy, in treatment, 86 Breathing, Biot's, in acute fatal type, 45 „ ,, in posterior basic meningitis, 60 „ cerebral, 18 „ ,, in posterior basic meningitis, 60 „ Cheyne-Stokes, 18 „ „ in acute fatal type, 46 ,, ,, in fulminating type, 42 Bromidia for sleeplessness, 87 Bronchitis, 26 Broncho-pneumonia, 26 „ „ in sub-acute type, 101 Cape To^vn, fourth epidemic period in, 8 Capsules, around meningococci, 148 Carpliology, in acute stage, 15 „ in hydrocephalus, 56 „ value in prognosis, 67 Carriers, definition of, 121 ,, discovery of, 132 ,, examination of throat of, 137 „ importance of, in propagatmg disease, 3, 11 ,, in normal communities, 120 „ temporary and prolonged, 136 test for, 165 „ variations in numbers of, 120 Cases, meningococcus in throat of, 124 Catarrh, naso -pharyngeal, 26 Catarrhal stage, 122 Causative agent, 90 Cellular changes in cerebro-spinal fluid, 112 Cerebral abscess, differential diagnosis of, 38 „ breathing, 18 „ „ in posterior basic meningitis, 60 Cerebro-spinal fluid, alteration of chemical constituents of, 111 General Index 209 Cerebro-spinal fluid, at onset, prognostic value of, 60 causes of increased pressure in, 103 cellular changes in, 112 circulation of, 96, 103 complete evacuation desirable, 81 differential count of cells in, 113 importance of study of, 108 in acute fatal type, 46 ,, type with recovery, 48 in influenza, 35 in suppurative type, 51 in tubercular meningitis, 37 inciease in sub-acute type, 100 „ of albumen in, 112 incubation of, 114 normal, 108 reducing substance in, 109 unrelieved tension of, causing sequelae, 71 yellow, 111 Chains, false, of gram-negative cocci, 141 Chemical constituents of cerebro-spinal fluid, 108 „ ,, ,, ,, alterations in, 111 Cheyne-Stokes breathing, 18 ,, ,, in acute fatal type, 46 „ „ in fulminating type, 42 Children, chief incidence among, 128 Choroid plexus, secretory scource of cerebro-spinal fluid, 96 Chronic meningitis, 56 „ types, 50 „ „ intermittent form, 67 „ ,, morbid anatomy of, 101 Circulation of cerebro-spinal fluid, 96 Cisternae of brain, anatomy of, 93 Classification, by agglutination reactions, 147 ;, of Elser and Huntoon, 147 ,, of gram-negative cocci, 144 Climate, influence of, 11 Clot, gelatinous, m cerebro-spinal fluid, 112 Clothing, effect of shortage of, 126 ,, spread of disease by, 130 Cold incubator test, at 23° C, 146, 152, 158 Coliform organism, with colony like meningococcus, 144 Colony, appearances of, of giam-negative cocci, 143 ,, ,, of meningococcus, 151 Coma, headache replaced by, 14 „ in acute stage, 15 „ fatal type, 45, 46 -, ., type with recovery, 48 ,, in fulminating type, 41 ., on third day, 65 Complement fixation of patient's serum, 107 ., ,, tests to differentiate meningococcus, 167 Complications, rarity of, in adults. 103 Compression in acute fatal type, 46 Conditions of epidemic outbreak, 125 Congestion of cerebral vessels in acute fatal type, 98 ,i ,, ,, in fulminating type, 98 Conjunctivitis, 24 Constipation, 27 Contact, definition of, 121 „ isolation of, 133 Contagion, direct, 119, 138 Contamination, by gram-negative cocci of air, 142 Convalescence, early establishment of, 66 F. & G. 14 210 General Index Convalescence from other diseases, onset during, 14 Convalescents, as carriers, 124 Convulsions, at onset of posterior basic meningitis, 59 „ in acute fatal type, 45, 46 ,, in fulminating type, 41 Cord, anatomy of membranes of, 94 Corfu, second epidemic period in, 6 Corn-starch medium, 150 ,, sugar medium, 160 Coryza, onset of acute type preceded by, 47 Course of the disease, 64 Crisis, in cases with gradual recovery, 51 ,, termination by, 66 Cultural characteristics, 91 Culture of cerebro-spinal fluid, 115 „ of menmgococcus. 149 „ ,, an indication for puncture, 82 „ „ from post-mortem material, 102 Cupping, in earlier methods of treatment, 72 Curschmaun's solution, hypodermic use of, 87 Cyanosis, 27 „ in acute fatal type, 46 „ in fulminating type, 42 „ value in prognosis, 67 Cystitis in hydrocephalus, 102 Dangers of lowering cerebro-spinal pressure, 82 „ of serum injection, 79 „ of transport negligible, 85 Deafness, 24 ,, in convalescence, 70 „ in posterior basic meningitis, 61 Definition of cerebro-spinal fever, 1 DeHrium, coexistent with headache, 15 „ in the acute stage, 14 ,, in acute fatal type, 45 „ „ type with recovery, 47 ., in fulminating type, 41 „ in hydrocephalus, 56 „ maniacal, in acute fatal type, 45 „ on third day, 65 „ value in prognosis, 67 „ tremens, differential diagnosis from, 40 „ „ onset simulating, 15 Denmark, second epidemic period in, 6 Desiccation, effect on meningococcus, 119, 152 Despatch of swabs, uselessness of, 135 Diagnosis, 28 „ differential, 34 „ „ dependent on bacteriology, 91 ,, in the post-mortem room, 102 Diarrhoea, at onset, 14, 27 Differential count of cells in cerebro-spiaal fluid, 113 Diplopia, 23 Direct infection, 124 Discharges, di-infection of, 85 ,, purulent from nose and throat, 26 Disinfectants, effect on menmgococcus, 153 Disinfection of discharges, 85 ,, of linen, etc., 132 Disseminated sclerosis simulated by convalescent cases, 23 Dosage of serum, 80 Drainage normal, re-estabUshment of, 58 re-establishment, the cause of crisis, 66 General Index 211 Dry tap, 33 Drying, effect on meningococcus, 119, 152 Dyspnoea, urgent in fulminating oases, 18. 27, 42 value in prognosis, 67 Early treatment, importance of, 65 East Africa, epidemic in, 11 Edinburgh epidemic, 10 Emetics in earlier methods of treatment, 72 Endocarditis, 27, 104 English epidemic of 1915, 10 ,, ,, Flexner's sernm in, 74 Epidemics, 1 ,, conditions producing, 125 Epidemic periods, 3 • ,. stage of, value in prognosis, 69 Erroneous fermentation results, 159, 160 Erjrthema, fugitive, 19 ,, in acute fatal type, 45 Evacuation of cerebro-spinal fluid desirable, complete, 81 Exacerbations, 67 External hydrocephalus, 60 Extracellular cocci, importance of, 115 ., ., value in prognosis, fiS Failure of early forms of treatment. 73 ,, of serum treatment in 1915, 76 Fatigue, influence on susceptibility, 128 Feeding, difficulty in, 20 „ nasal, 86 „ of hydrocephalic cases, 56 ,, rectal, 86 Fermentation reactions, characteristic rates of, 146, 158 „ ,, of gram-negative cocci, 160 „ „ of meningococcus, 161 „ ^ ,,- of micrococcus catarrhalis, 162 „ ,, use in classification, 144, 158 Fever, indication for puncture, 82 „ intermittent in acute type with recovery, 49 ,, resemblance to ague, 16, 52 ,, value in prognosis, 67 Fifth epidemic period, 8 Fijian Islands, fourth epidemic period in, 8 Film preparations, importance of number of cocci in, 115 „ „ meningococci in, 113 „ „ staining of, 114 First clinical description, 2 „ day of iUness, 64 ,, epidemic wave, 3 Flaccid paralysis, 23 Flexner's serum, 73 Fluid culture, growth of meningococcus in, 150 Foreign proteid, introduction of, in serum treatment, 77 Four groups of Gordon, 165 Fourth epidemic period, 8 „ ventricle, adhesion of roof of, 58, 102 France, first epidemic wave in, 4 ,, second epidemic wave in, 4 ,, fifth epidemic wave in, 9 Frequency of serum injections, 81 Fulminating type, 41 „ „ microscopical pathology of, 98 ,, ,, morbid anatomy of, 97 „ „ nature of, 42 14—2 212 General Index Fulminating type, onset of, 13 Gee and Barlow's disease, 59 Gelatinous clot, in oerebro-spinal fluid, 112 General reaction of body, 105 General treatment, 85 Geneva epidemic, 2 Geograpliical distribution, 11, 129 Germany, third epidemic wave in, 7 ,, fifth epidemic wave in, 9 Glasgow epidemic, 10 Glucose in cerebro-spinal fluid, 109 „ „ „ diminution of, 112 Gonococcal meningitis, doubtful occurrence of, 144 Gonococcus, characters of, 146 ,, differentiation from meningococcus, 144 Gordon's four groups, 165 Gram's stain, method, 141 Gram-negative diplococci, gram -positive foims of, 142 of the air, 142 „ „ the group of, 139 Gram-positive cocci of Jaeger and Heubner, 142 ,, forms in meningococcus cultures, 148 ,, ,, of the gram-negative cocci, 142 Granular staining of meningococcus, 148 Greece, third epidemic period in, 7 Group agglutinations, 164 Grouping of strains, 165 Haematogenous origin of disease, 153 Haematuria, 27 Haemophilia, exclusion of meningeal haemorrhage in, S Haemorrhage, meningeal, differential diagnosis of, 39 Head, nodding of, 21 „ retraction of, 21 „ „ absent in fulminating t3'pe, 42 „ „ in acute fatal t3'pe, 45 I, ,, ,, typs with recovery, 48 „ „ in hydrocephalus, 56 „ „ in posterior basic meningitis, 60 „ „ index of intracranial pressure, 49 „ „ on third day, 65 ,, „ value in prognosis. 67 Headache, an indication of increased pressure, 57 „ „ for puncture, 81, 87 „ at onset, 14 „ co-existent with delirium, 15 „ in acute fatal type, 44 „ ,, type with recovery, 47 „ in convalescence, 70 „ in hydrocephalus, 55 ,, intense in fulminating form, 41 ,, on first day, 64 „ treatment of, 86 Heart, little toxic effect on, 154 Hemiplegia, 23 ,, in acute fatal type, 45, 40 Herpes, 20 „ in acute fatal type, 46 ,, „ typG \vith recovery, 48 ,, value in prognosis, 68 Hexamine, treatment by, 85 Hirsch's four epidemic periods, 3 His' medium, 160 General Index 213 History, 1 Hydrocephalic cry, in posterior basic meningitis, 60 „ symptoms, following scrum injection, 77 Hydrocephalus, 53, 54 ,, absence of cocci in cerebro-spinal fluid of, 103, 116 „ ,, pus in, 102 „ amoimt of pus in, 111 „ established in second or third week, 67 „ external, 60 „ in posterior basic meningitis, 59 „ morbid anatomy of, 101 „ \vith acute stage wrongly diagnosed, 59 „ „ recovery, 57 Hydrocyanic acid for vomiting, 87 Hyperaesthesia, 23 Hypersecretion of choroid plexuses, 97 Hypophysial gland, as path of infection, 105 Ice to the head in treatment, 72, 78 Iceland, second epidemic period in, 6 Imbeciles, 25 Improvement, early signs of, 66 Inagglutinable strains, 163 Incubation of cerebro-spinal fluid, 114 „ period, 62 Incubator, travelling, 135 India, outbreaks in, 11 Infection, direct, 124 „ distribution of. in meninges, 102 path of, 104 „ site of, 100, 117 Influenza, cerebro-spinal fluid in, 35 „ differential diagnosis from, 34 „ increased cerebro-spinal pressure in, 110 Inhibition of growth of meningococci, 151, 152 Inoculation, subdural in animals, 153 Intermittent carriers, 136 Intracellular position of gram-negative cocci, 143 Intracranial pressure, increase in acute fatal type, 45, 46 „ „ „ ,, type with recovery, 48 „ ,, sudden rise at onset, 14 Intramuscular injection of serum, 83 Intrathecal serum administration of Flexner, 73 Intravenous injection of serum, 83 Intraventricrdar puncture in hydrocephalus, 117 Iodide of potassium, treatment by, 73, 86 Ireland, third epidemic period in, 7 Iritis, 24 Iridochoroiditis, 24 Iridocyclitis, 24, 104 Irregularities in size and staining of meningococcus, 140 Isolation of contacts, 133 „ of patients, 130 ,, of prolonged carriers, 136 Italy, second epidemic period in, 5 Jochmann's serum, 73 Keen's operation to drain ventricle, 89 Keratitis, 24 Kernig's sign, 22 „ ,, importance of, on second day, 64 „ „ in acute fatal type, 45 ,, ., „ type with recovery, 48 214 General Index Kernig's sign, in cases of gradual recovery, 52 in fulminating type, 42 in posterior basic meningitis, 60 normal in infants, 22 the indication of meningeal infection, 54 value in diagnosis, 29 Knee jerks, 23 Kocher's operation for draining ventricle, 89 Landes, the, origin of second epidemic period in, 4 Large and small colonies of meningococci. 151 Lateral sinus thrombosis, differential diagnosis of. 39 Lateral ventricle, operations to drain, 88 Leeches in treatment, 72, 87 Leucoc3^osis, 105 London, fourth epidemic period in, 8 Lumbar puncture, anatomical points in, 95 general anaesthetic in, 30 in acute fatal type, 46 ,, type with recovery. 48 in adynamic state, 55 in cases of gradual recovery, 52 in hydrocephalus, 55, 103 in suppurative type, 50 indicated by Kernig's sign, 23 introduction of, 28 lateral operation for, 32 operation of, 29 position of patient for, 32 remote effects of, 83 symptoms justifying, 28 fluid, sudden diminution in hydrocephalus, 57 Lysis, termination by, 66 MacEwen's sign, 56 „ „ in posterior basic meningitis, 60 Macular rash, 18 „ ,, in acute fatal type, 36 „ „ „ type with recovery, 48 ,, ,, value in prognosis, 68 Manometer, for cerebro-spinal fluid, 34 Measles, differential diagnosis from, 36 Medico-legal aspect of fulminating case, 42 Medulla, pressure on, in hydrocephalus, 56 Membranes of brain, anatomy of, 92 ,, of cord, anatomy of, 94 Meningitis, gonococcal, doubtful occurrence of, 144 „ pneumococcal, differential diagnosis from, 38 ,, purulent, differential diagnosis from, 38 ,, staphylococcal, differential diagnosis from, 38 „ streptococcal, differential diagnosis from, 38 ,, tubercular, cerebro-spuial fluid of, 37 ,, ,, differential diagnosis from, 37 Meningococcus, a group of related organisms, 107, 140 „ characters of, 146, 148 ,, discovery of, 28 „ in film preparations, 113 „ sugar reactions of, 161 Mental condition, following cerebro-spinal fever, 25 Mental depression in isolated carriers, 136 Mental enfeeblement, 58 Mercury in treatment, 86 Metachromatic granules in meningococcus, 148 Micrococcus catarrhalis, characters of, 146, 157 General Index 215 Jlicrococcus catarrhalis, in posterior pharynx, 140 „ „ sugar reactions of, 162 ,. flavus I chaiacters of, 145, 156 „ „ IT ., 145 156 „ III „ 146, 157 ,, pharyngis siccus, characters of, 145, 155 Microscopical pathology of acute fatal type, 99 ,, ,, of fulminating type, 98 Micturition, difficulty of, in early stage, 20 Mild oases, absence of cocci in cerebro-spinal fluid of, 116 Milk, growth of meningococcus in, 151 Monoplegia, 23 Morbid anatomy of acute fatal type, 98 ., „ of chronic type with hydrocephalus, 101 „ „ of fulminating type, 97 ., „ of palsy in children, 104 ,, „ of sub-acute type, 100 ,, „ of suppurative type, 100 Morphia for headache, 86 ., „ vomiting, 87 ,, to diminish risk to attendants, 132 Morphology of the gram-negative cocci, 140 Mortality, in posterior basic meningitis, 61 ,, severe in earlier epidemics, 72 Mumps, differential diagnosis from, 36 Muscles of neck, stiffness at onset. 21 ., „ „ on second day, 64 MiLscular rigidity at onset, 21 „ „ in fulminating type, 42 „ „ in hydrocephalus, 56 „ „ on third day, 65 Myelitis, acute, differential diagnosis from, 40 Myocarditis, 27 Nasal cavity, connection with sub -arachnoid space, 94, 105 „ douche, 137 „ feeding, 86 ,, irrigation, necessity of, 185 „ ,, „ „ for attendants, 132 Naso-pharynx, meningococcus in, 119 „ ,, of cases, meningococcus in, 124 Neck, muscles of, stiffness at onset, 21 ,, ,, „ on second day, 64 Needle, Barker's, for lumbar puncture, 31 Nerve, facial, involvement of, 23 „ hypoglossal, involvement of, 23 „ cells, condition of, in acute fatal type, 99 Neutral red as indicator, 159 New York, epidemic of 1905 in, 125 Nomenclature, 1, 90 Normal communities, carriers in, 120 Nourishment in acute stages, 85 Number of cocci in fihns, effect of serum on, 115 ,, „ „ importance of, 115 ,, of lumbar punctures necessary, 82 Nursing, precautions in, 132 Nutrition, general influence on infection, 127 Nutrose agar, best for plates, 149 Nystagmus, 23 Occlusion of sub-arachnoid space, 109 Odyssey of 18th Light Infantry, 5 Olfactory lobes, in acute fatal type, 98 „ nerves, as path of infection, 104 216 General Index Onset, 64 „ in acute fatal tj^pe, 44 ,, „ type with recovery, 47 „ in fulminating type, 41 „ of hydrocephalus, 55 ,, of posterior basic meningitis, 59 „ suddenness of, 13 Operations, for, hydrocephalus, 87 Ophthalmia, purulent, 24 Opisthotonos, 22 ,, in posterior basic meningitis, 59, 60 Opium in earlier methods of treatment, 73 Opsonic index of patient, 106 ,, tests for differentiation of meningococcus, 167 Optic atrophy, 24 ,, after soamin, 85 „ rarity in posterior basic meningitis, 60 discs, in hydrocephalus, 56 lobes, pressure on, in posterior basic meningitis, 60 neuritis, 24 ,, in posterior basic meningitis, 60 Otitis media, 25 Overcrowding, effect on individual, 126 ,, importance - of , 12 Pacchionian bodies, absorption through, 96 „ „ anatomy of, 92 Pain in back, as sequela, 58 ,, ,, and legs iu convalescence, 71 ,, „ ,, thighs at onset, 20 Palsy, 23 „ as sequela, 58 ,, in children, morbid anatomy of, 104 „ in convalescence, 70 „ treatment of, 87 Panophthalmitis, 24, 104 Para-meningocoocus, characters of, 146 ,, differentiation of, 166 „ sugar reactions of, 161 Path of infection, 104 Pathogenicity of meningoooeous to animals, 153 Pathology, 90 Patients' serum, agglutinative power of, 78 ,, ,, intrathecal injection of, 78 Perivascular haemorrhage in acute fatal case, 1 „ infiltration of brain, 99 „ „ of cord, 99 Permanent carriers, 136 Petechial fevers, possible identity of, 2 „ rash, 19 ,, „ in acute fatal type, 45 :, „ in fulminating type, 42 ,, ,, value in prognosis, 67 ' Pharyngitis, differential diagnosis from, 36 Pharynx, posterior, meningococcus in, 104 Photophobia, as an early symptom, 14 Physical conditions, importance in culture^ 150 Pigmentation of cerebro-spinal fluid, 112 „ punctiform, of colonies of gram-negative cocci, 143 ,, ,, of meningococcus colony, 150 Plague spot, 20 Plantar reflex, 23 Plate culture, investigation of, 167 „ ,, method of sowing swab on, 134 General Index 217 Plate holder, sterilizable, 133 Pleurisy, 27 Pneumococcal meningitis, 38 Pneumococcus, terminal infection by, 38 Pneumonia, differential diagnosis from, 35 ,, increased cerebrospinal pressure in, 110 ,, lobar. 27 Poisonings suspicion of, in fulminating cases, 42 Polioencephalitis, differential diagnosis from, 40 Pohomyelitis, differential diagnosis from, 40 „ not differentiated in earl}' epidemics, 7l Portugal, fifth epidemic wave in, 9 Position of patient for lumbar puncture, 32 Posterior basic meningitis, 59 „ „ ,, a disease of infants, 128 „ „ ,, chronic course of, 60, 61 „ „ ,, identity with chronic type. 103 ,, ,, ,, recognition in fifth period. 8 ,, „ ,, usual form in England, 91 Posterior pharynx, meningococcus in, 104 Precipitin reactions, )67 Predisposing causes of infection, 125 Pressure, cerebro-spinal, increase, causes of, 103 „ „ „ in the disease. 109 , ,, „ indicated by headache, 57 „ ,, ,, other diseases, 110 „ „ normal, 108 „ „ on meduUa in hydrocephalus, 56 „ ,, replacement of, in serum treatment. Preventive measures, 130 Previous illness, a predisposing cause, 126 Prognosis, 67 „ remote, 70 Prolonged carriers, 121 ,, „ isolation of, 136 Prostration, prevention of, 87 Proteolysis, by meningococcus, 162 Pseudo-meningococcus, 165 ,, . carriers, 168 Pulse, 16 „ during serum injection, 79 ,, in acute fatal type, 44 „ „ type with recovery, 47 „ in fulminating form, 42 „ in hydrocephalus, 55 ,, irregularity of, 17 ,, respiration ratio, 18 „ running, 17 ,, slow with high temperature at onset, 17 ,, value in prognosis, 67 Pupils, condition of, 24 Purpuric rash, 19 „ ,, in fulminating tj^pe, 42 ,, „ value in prognosis, 67 Purulent meningitis early in disease, 43 Pus, amount in cerebro-spinal fluid. 111 Pyehtis, 27 Pyrocatechin in cerebro-spinal fluid, 109 Rainfall, in relation to the disease, 129 Eash, serum, 80 J, varieties of, 18 Ratio, pulse-respiration, 18 Rectal feeding, 86 218 General Index Reducing substance in cerebro-spinal fluid, 109 Reflexes, abdominal, 23 „ plantar, 23 „ superficial, 23 Relapse, 53 Relapsing cases, 58 Relief of symptoms after puncture, 110 Remote prognosis, 70 Replacement of pressure in serum treatment, 77 Respiration, 18 Riot's, IS ,, during serum injection, 79 „ in acute fatal type, 45 „ „ type with recovery, 47 „ in fulminating type, 42 Respiratory failure, 18 „ „ due to increased pressure, 110 „ „ in acute fatal type, 46 Restlessness, in the acute stage, 15 „ value in prognosis, 67 Retention of urine in acute fatal type, 45 ,, ,, ,, type with recovery, 48 „ „ in early stage, 20 „ ,, in fulminating type, 42 • „ „ in hydrocephalus, 55 ,, „ value in diagnosis, 29 Retraction of head, 21 „ „ absent in fulminating type, 42 „ ,, in acute fatal type, 45 „ ,, „ type with recovery, 48 „ ,, in hydrocephalus, 56 „ „ in posterior basic meningitis, 60 ,, „ index of intracranial pressure, 49 „ „ on third day, 65 ,, ,, value in prognosis, 67 Rigidity, muscular, at onset, 21 ,, „ in fuhninating type, 42 ,. „ in hydrocephalus, 56 „ ,, in posterior basic meningitis, 60 ,, ,, on third day, 65 Rigor at onset, 13, 64 „ in acute fatal type, 44 „ „ type with recovery, 47 „ in fulminating type, 41 „ in hydrocephalus, 55 Russia, third epidemic period in, 7 Scarlet fever, difi'erential diagnosis from, 36 Screaming at onset of posterior basic meningitis, 59 Seaport as starting place in an epidemic, 11 Seasonal distribution of disease, 129 „ weather conditions, effect on susceptibiUty, 126 Second day of illness, 64 „ epidemic period, 4 Septicaemia in early stage, 43, 92 „ initial, as path of infection, 105 „ meningococcal, 42, 104, 117 „ „ post-mortem appearances in, 97 Septicaemic stage, 122 Sequelae of hydrocephalus, 58 „ rarity of, 71 Serum, dosage, 80 „ injections, frequency of, 81 „ intramuscular injection of, 83 General Index 219 Serum, intravenous injection of, 83 ,, introduction to ventricles, 88 „ methods of injection, 78 „ of patient, bactericidal power of, 107 „ ,. intrathecal injection of, 52, 107 rash, 80 „ subcutaneous injection of, 83 ,, treatment, effect on cocci, 115 ,, „ indications for suspension of, 81 Shifting population, importance of, 12 ,, ,, in epidemics, 125 Shock, during serum injection, 80 ,, from lumbar puncture, 82 Sicily, second epidemic period in, 6 Sinuses of nose as harbours for meningococcus, 122 Site of meningococcal infection, 100 Size of gram-negative cocci, variations in, 140 SmaU-pox, differential diagnosis from, 36 Soamin, treatment by, 84 Sore throat, onset preceded by, 47 Source of cocci in cerebro-spinal fluid, 117 Specific agglutinins, 164 „ fevers, cerebro-spinal fever a sequel of, 36 Sphenoidal sinuses as harbours of meningococcus, 122 „ ,, as path of infection, 104 Sphincters, involvement of, 20 Sporadic appearance of disease, 123 ,, cases, 1 Spread of disease by prolonged carriers. 121 „ method of, 130 Spreading of plate cultures, 135 Spring, cerebro-spinal fever a disease of, 129 Stab culture, advantages of, 150 Stage ot epidemic, value in prognosis, 69 Staining after macular rash, 19 „ of films from cerebro-spinal fluid, 114 ,, of gram-negative cocci, 140 Staphylococcal meningitis, 38 Staphylococci, gram-negative cocci belonging to, 141 Starch medium, 150 „ sugar medium, 160 Sterilizable plate-holder, 135 Sterilization of fluid media, difficulties of, 158 Stippling of meningococcus colonj', 150 Strabismus, 23 Streptococcal meningitis, 38 Streptococci with colonies lite meningococcus, 144 Strychnine, hypodermic use of, 87 Stupor in acute stages, 15 Sub-acute types, 50 „ ,, morbid anatomy of, 100 Sub-arachnoid space, anatomy of, 92 „ „ obstruction of, in hydrocephalus, 57 „ „ of cord, 95 ,, ,, operation to drain, 89 ,, „ prolongations into nose, 94, 105 Sub-culture, essentials for, 150 „ necessity of, from sugar media, 161 Subcutaneous injection of saline, 87 . ,, ,, of serum, 76, 83 Sub-dural inoculation in animals, 153 Subsultus tendinum in acute stages, 15 „ „ in fulminating type, 42 „ „ in hydrocephalus, 56 220 General Index Sugar, in cerebro-spinal fluid, 109 „ „ „ diminution of, 112 „ media, composition of, 169 „ „ difficulty of sterilizing, 158 solid, 159 „ reactions, cliaracteristic rates of, 146, 158 „ „ of gram -negative cocci, 160 „ ,, of meningococcus, 161 „ „ of micrococcus catarrhalis, 162 ,. ,, use in classification, 144, 158 Summer, rapid decline of epidemic in, 129 SunUght, eflfeot on meningococcus, 152 „ gram-positive forms produced by, 143 Superficial reflexes, 23 Suppurative type, 50 „ „ amount of pus in, 111 ,, „ course of, 66 ,, „ morbid anatomy of, 100 Suprarenal capsules, haemorrhagic, 98 Surgical procedures in posterior basic meningitis, 61 Susceptibility of individual, changes in, 125 Suspension of serum treatment, indications for, 81 Swab, convenient form of, 134 „ method of taldng, 133 „ uselessness of despatch of, 135 „ West's covered, 133 Swallow, inability to, 20 ,. „ in acute fatal type, 46 „ ,, ,, .type with recovery, 48 Sweating in acute fatal type, 46 „ in fulminating type, 42 Sweden, third epidemic period in, 6 Symptoms, 13 „ aggravation of, following serum injection, 77 „ ,, on third day, 46 „ diminution of, on second day, 45 „ justifying lumbar puncture, 28 „ rehef of, after lumbar puncture, 110 Tache cerebrale, 24 Tapping the ventricles, operation for, 88 Temperature, course of, in the disease, 16 „ daily variations in atmospheric, 129 „ in acute fatal type, 44 „ „ type with recovery, 47 „ in fulminating type, 42 „ in hydrocephalus, 55 Temperatures of growth of meningococcus, 152 Temporary carriers, 121, 136 ,- „ treatment of, 136 ;, improvement on second day, 64 Tenderness in muscles of neck at onset, 21 ,, „ „ on second day, 64 Terminal invasion in hydrocephalus, 57 „ ,, in posterior basic meningitis, 61 Termination by crisis, 66 „ by lysis, 66 Tetanus, differential diagnosis from, 37 Tetrads, meningococci in, 143 Theca, adhesion of, in hydrocephalus, 102 Third day of iUness, 65 „ epidemic period, 6 Throat, local treatment of, 137 „ normal, meningococcus in, 91 General Index 221 Throats of cases, meningococcus in, 124 „ of nurses, examination of, 132 Thrombosis of venae Galeni as cause of hydrocephalus, 59 TonsUhtis, differential diagnosis from, 36 Toxaemia, in acute fatal type, 45 „ in fulminating type, 41 Toxins of meningococcus, 154 Transient carriers, 121, 136 ,, ,, treatment of, 136 Transport, dangers of, negUgible, 85 Transvaal, epidemic, in, 11 Travelhng incubator, 135 Treatment, 72 ,, by lumbar puncture alone, 75, 76, 81 „ failure of early forms of, 73 „ „ of serum in 1915, 76 „ general, 85 „ of cases, precautions in, 130 „ prognostic value of date of, 68; 78 Trismus, 22 Troops, virulence of epidemics among, 128 Typhoid fever, differential diagnosis from, 35 Typhus, differential diagnosis from, 36 Unconsciousness at onset, 13 „ „ value in prognosis, 67 United Kingdom, second epidemic wave in, 6 fifth „ „ 9 United States, first „ second third „ „ 7 fifth „ „ 9 Urine, disinfection of, 132 ,, incontinence of, 20 ,, ,, in acute fatal type, 46 „ presence -of meningococcus m, 92, 118 ,, retention of. in acute fatal type, 46 „ „ ,, type with recovery, 48 „ „ in early stage, 20 ,, „ in fulminating type, 42 „ „ ■ in hydrocephalus, 55 ,, ,, value in diagnosis, 29 Urotropin, 86 , Vaccination, protective, 84 Vaccine treatment, 83 Vaso-motor changes, 24 Vedder's medium, 150 Veins of eye, fullness of, 24 Venesection in earlier methods of treatment, 72 Ventilation, necessity of free, 85 „ „ „ in treatment, 131 Ventricles, cerebral, in acute fatal type, 99 „ „ in hydrocephalus, 101 ,, „ operation for tapping, 88 Vibices, 19 Vines' sugar medium, 159 Virulence, high among troops, 128 „ low, under normal conditions, 91 VitaUty not corresponding to staining power, 141 „ of gram-negative cocci, 143 „ of meningococcus, 151 „ on swabs, 136 Vomiting at onset, 13, 14 '222 General Index Vomiting in acute fatal type, 44 „ „ type with recovery, 47 „ in fulminating type, 41 „ in hydrocephalus, 56 ,, in posterior basic meningitis, 60 „ indication for puncture, 82 ,, on first day, 64 Wasting, in acute stage, 25 „ in hydrocephalus, 56, 102 „ in posterior basic meningitis, 60 Weather conditions, seasonal, effect on susceptibility, 126 West Africa, epidemic in, 10 West's covered swab, 133 Winter, cerebro-spinal fever a disease of, 129 YeUow cerebro-spinal fluid. 111 CAMBEIDGE; PRINTED BY JOHN CLAY, M.A. AT THE UNIVERSITY PRESS Work by the late Sir MICHAEL FOSTER Lectures on the History of Physiology during the Sixteenth, Seventeenth, and Eighteenth Centuries With a frontispiece. 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