THE PRACTITIO!

JANUARY, 1916.

 

TREATMENT OF CEREBRO-SPINAL MENINGITIS.*

(a) By Sir WILLIAM OSLER, Bart., M.D., F.R.S.
Regius Professor of Medicine, Oxford University, etc.

For the first time in the medical history of these islands,
cerebro-spinal fever has prevailed as an epidemic, with the
usual characteristics, 7.¢., a low case-incidence, a widespread
yet capricious distribution and predilection for soldiers, parti-
cularly young soldiers, a high case-mortality, and a rapid
disappearance of the disease with the approach of fine weather.
The figures of its distribution and prevalence are not yet
available. As usual in Europe, the military population has
suffered most. In the first year of the war there were, in the
home Army, 462 deaths, which places the disease second on
the list of causes of death from acute infections—probably a
very much larger proportion than among the civil population.
‘When the returns are made, it will be seen that the deaths
. from cerebro-spinal fever form but a small proportion of the
total deaths from meningitis. I hope that one result of the
careful studies recently conducted will be a more accurate
registration of the forms of the disease.

For the year 1913, the Registrar-General reported 9,269
deaths from meningitis in England and Wales. More than
half, z.e., 5,018, were the tuberculous form. Of the balance,
159 were classified as posterior basic, 163 as cerebro-spinal
fever, and 3,819 as ‘‘other forms.’’ More information is
needed concerning this last group, in which a not inconsider-
able number may be due to the meningococcus. Cerebro-
spinal fever is not only interesting as an epidemic, but as a
meningitis it has the fortunate distinction of being the only
variety from which recovery takes place in from 50 to 70 per
cent. of the cases. Many men of large clinical experience
have never seen recovery in the tuberculous, pneumococcic,

.* This symposium is based upon a recent discussion at the Royal Society

of Medicine; each paper has been specially revised and amplified by the
author for this number of THz PracTITIONER.

A
2 THE PRACTITIONER.

or streptococcal varieties. I have not myself had a recovery
in cases under my care of any of those three forms. I have
seen one case of doubtful tuberculous meningitis recover ;
and I saw, last autumn, at the Cleveland Hospital, one case
of streptococcal meningitis recover. It was determined to be
streptococcal by that streptococcus specialist, Dr. M. H. Gordon.
The meningococcus is always present. It may be grown in
pure culture; it has specific serological reactions, and the
disease may be reproduced in animals. It has “ strains,”
which, however, have not yet been worked out satisfactorily,
neither has their existence yet been sufficiently considered,
seeing that they present differences in agglutination, opsoniza-
tion, and complement fixation. I hope that matter will be
cleared up in the present investigation.

Two points call urgently for discussion : the prophylactic
measures, and the serum treatment. The others, in. com-
parison, are subsidiary and unimportant.

We may, I think, expect a return of the disease this
winter. There are instances of a progressive yearly increase
in the virulence of the epidemic. What preparations should
be made in the prospect of such a renewal? Let us
recognize a certain value in the conception of the disease
propounded originally by Dopter, and supported in this
country, among others, by Arkwright, Lundie, Thomas,
Fleming, and Maclagan. These men hold that the epidemic
is in the carrier; the meningitis is regarded by them as an
incident. The germ is ubiquitous, and is harboured by many
who show no symptoms of the disease, but producing in others
a mild catarrh, and only in a few reaching the meninges.
This is what happened in the case of pneumonia, in which
the proportion of cases to carriers is even smaller than in the
case of cerebro-spinal fever. The germs may be present in
the throat without the occurrence of naso-pharyngeal catarrh ;
it may be present in a severe case of the disease, without any
indication other than that obtained by cultures.

Two broad facts stand out :

(x) The correlation of the seasonal prevalence with naso-
pharyngeal catarrh, and

(2) The influence of overcrowding in ill-ventilated
barracks and houses.

The concentration of human beings, particularly of young
recruits in camps, seems to me to be the most important single

CEREBRO-SPINAL MENINGITIS. 3

-factor. Fatigue lowers resistance, wet and cold and the

excessive use of tobacco favour pharyngeal catarrh ; too often
the huts and tents are overcrowded, nights are cold, blankets
thin; what wonder that the men close the windows, and lace
up the tents tightly, so that the air becomes foul. The carrier
does‘the rest, distributing the germ to a young fellow whose
resistance is weakened, or whose naso-pharynx forms a suit-
able medium.

During next winter, medical officers in charge of camps and
‘barracks and of men quartered in houses should do three
things ; -

(x) Guard the young soldier especially against over-
fatigue. I know that is a very easy thing for me
to say, and a very hard thing for the medical officer
to ensure.

(2) Reduce to a minimum the circumstances favouring
naso-pharyngeal catarrh.

(3) Make possible a combination of good ventilation of
sleeping quarters with comfortable warmth for the

/ men.

You can get comfortable warmth and good ventilation
combined, but you cannot secure comfortable warmth in
many of the conditions in which the men are. I saw once six
men in a room in which I would not put three; they were
quartered in villas. The windows were shut, and the door
was shut until I opened it; the men were sleeping on
‘mattresses on the floor. One of them said, “ We have got
to shut the window to keep ourselves warm.” I think the
public health authorities and the medical officers in charge
of camps should bear these points in mind, with reference to
the possibility of a recurrence of the disease this winter.

The prophylactic use of anti-meningitic serum is still on
trial; we do not know enough to recommend it or to dis-
courage it. I hope this discussion will elicit the results which
have been achieved by those who have employed it. On
present knowledge, specific therapy combined with lumbar
puncture is the rational treatment, combating the sepsis by
means of the one and the pressure effects of the local exudates
by the other means. We are agreed as to the value of with-
drawal of fluid from the spinal meninges. On the value of
specific therapy, however, there is a grave difference of opinion.
The use of the serum is based on sound experimental data.

A2
4 THE PRACTITIONER.

The long study of Flexner and his pupils and others have made
possible the production of a serum which has a specific influence
on the meningococci in the spinal canal, partly by a direct
bacteriacidal action, partly by bringing about phagocytosis ;
and there may be an antitoxic action. No one can have
followed the work at the Rockefeller Institute on the meningitis
problem, without having been impressed with the fact that it is
solid, sound, good work, and that, if there is any truth in the
serum therapy, it is just on such researches that it must be
based. The specific treatment has been in use for some years
and details of the results are readily to be found, particularly in
the recent monograph of Sophian ; the last table in his book
gives the collected statistics of cases treated with, and without
the serum, and, if they are worth anything, the figures show an
overwhelmingly strong case for specific therapy.

The practical points for us to discuss are, first, the ex-
perience of the past few months ; and, secondly, its lessons for
the future. We must be disappointed in many quarters with
the serum treatment. The reasons for the failure should be
laid open freely and frankly ; what we wish is to get a state-
ment of the truth of the matter. The consultant only sees
severe cases, and cases which are far advanced. It has been
said that when the cases reach us, they are in a condition to
receive “extreme unction.” The death-rate has been high
and I hope the figures for the whole country will be available.

I was much interested in the outbreak among Canadian
soldiers at Salisbury, where 40 cases were treated, with
26 deaths—a mortality of 63 per cent. The sera used were
from Burroughs Wellcome, Lister Institute, Mulford, and
Parke, Davis. It was said that a few of the patients
treated with Mulford’s serum suggested that some improve-
ment had taken place, but it was hardly striking enough to
justify its use. There was no benefit from the other sera. In
one case, the meningococcus was isolated two and a half months
after the illness, and after more than 20 intraspinal injections
had been given. In another case, meningococci were found in
the fluid five weeks after the onset of the illness, during which
there were 12 injections. This is the figure from one who is
an expert in the technique of intraspinal treatment. I have
seen it given by the gravity method, and with great -skill
Tnere were no better results at Haslar. There were 30 cases
there, with a mortality of 52 per cent., and the use of the serum

CEREBRO-SPINAL MENINGITIS. 5

was abandoned after eight deaths in 12 cases. Happily, the
man with the largest experience, Dr. Gardner Robb, of
Belfast, tells a different tale.

We want to know the reasons for this widespread failure.
I think there has been one main cause: inert sera. We do
not know in how many cases the parameningococcus was
present. That does not react to the ordinary antimeningitic
serum. There have been as well insufficient dosage, failure to
treat cases early, and imperfect technique ; these have been
minor contributory causes. There are, of course, cases which
resist all treatment. We cannot expect, by any form of
treatment of cerebro-spinal meningitis, to get a mortality
below 20 to 25 per cent. ; we have to deal with acute, malig-
nant, fulminating cases, which die in 24 to 36 hours ; and there
are some deaths from complications. But we have to face
the problem, that there is this extraordinary discrepancy
between the results obtained in many quarters in this country
and the results obtained by Flexner and others, in recent
epidemics in the United States and elsewhere. It may be a
question, as I suggest, of inert sera. I think this should be
made a War Office problem, and be placed by them into the
hands of experts who shall investigate sera, SO that we can be
certain that they correspond to the strain of organisms present

in the prevailing epidemic.

(b) By A. GARDNER ROBB, M.B., D.P.H.
Medical Superintendent, City Fever Hosptial, Belfast.

I HAVE always been greatly interested in this subject, for in
Belfast and the North of Ireland we have suffered severely
from outbreaks of this disease since 1907-

Before the introduction of the serum of Flexner, there
yecurred in Belfast a severe outbreak. In the first seven
months of that outbreak, J had under my care in the Fever
Hospitals 275 cases, and the death-rate was over 42, per cent
Then I received from Dr. Flexner a supply of the serum, on
the preparation of which he had been working for a long time.
It had already been tried in a few scattered cases in America
with good results. I began its use in the beginning of Sep-
tember, 1907. The change in results was dramatic. The
death-rate fell at once to one-third of what it had been. The
death-rate in our hospital cases had been over 80 per cent. in
6 , THE PRACTITIONER.

the three months immediately before the serum arrived. Of
45 cases admitted in those three months 37 had ended fatally.
In the first four months after the use of the serum was begun,
the mortality in hospital was 26 per cent. Only half the cases
occurring in the city at that time were sent into hospital,
and, during the same four months, the mortality in the cases
not sent into hospital, and not treated with serum, was 85 per
cent. Since then I have from time to time reported the results
I have obtained with Flexner’s serum, and in no series of cases,
up to the beginning of last winter’s epidemic, did the mortality
in our Belfast cases so treated exceed 30 per cent.

No one who has had any considerable experience in the
treatment of this disease without intra-spinal injections of
serum, and has then had an opportunity of observing the results
of such injections, can have any doubt as to the enormous
value of this treatment ; and I believe I am correct in stating
that every one who has had such opportunities is enthusiastic
regarding the success of this method of treatment. To this
I think there is not any exception, as shown by the writings
of Dunn, Emmett Holt, Ladd, Royer, Sophian, Fulton, and
many others in America; of Netter and Dopter in France ; of
Claude Ker of Edinburgh, and of Christomanos, with his
large experience, in Greece. The same unanimity is to be
found in the records from Germany, where similar success was
obtained after the adoption of the intra-spinal route for the
administration of the antiserum.

_ At the discussion in the Epidemiological Section, held here
last February, I reported my results to that date. The
number of cases was then about 120, and the mortality had
been under 24 per cent. These are gross mortality results,
all the deaths are included, and I would again plead that gross
mortality rates should be given in records of serum-treated
cases for two reasons. First, because the death-rates of 60 to
80 per cent. commonly reported in outbreaks in America and
Europe before the introduction of intra-spinal injections of
serum were gross mortality rates ; and secondly, because, from
my experience, I believe it is quite impossible to say in the
first few hours of illness that any case is hopeless.

In a recent and very excellent work on cerebro-spinal
meningitis, the author, who had large experience of the serum
treatment in a comparatively recent epidemic, and had a
gross mortality rate of 25 per cent., excludes over 40 per cent.

 
  
  

CEREBRO-SPINAL MENINGITIS. 7

| -of his fatal cases, because they were ‘‘ hopeless from the first,”
or died within 24 hours, etc. He then publishes a table of

cases reported from various places all over the world. The
mortality from these places is a gross rate, whereas the
author’s is a “corrected” rate. Naturally, his results are
about twice as good as those obtained by others.

_. Toillustrate how impossible it is to give a definite prognosis,
l-may be allowed to mention one case which occurred last
February. I was asked late one night to see a young man
who had only been taken ill that morning. He had been in ex-
cellent spirits on going to bed the night before, but was unable
to rise in the morning on account of severe headache ; he soon
became delirious, and then unconscious. When I saw him, some
15 or 16 hours after the onset, he was unconscious, the pulse
could not be counted -+ +he wrist, there was great rigidity, and
he was covered with large patches of subcutaneous hamorr-
hages anda plentiful petechial eruption ; on his feet were large
hemorrhages into the skin measuring 2 ins. by 3 ins., his
ears, hands, knees were covered with deep purple patches of
hemorrhage, and there were large sub-conjunctival hemorr-
hhages. Though it seemed doubtful to me and to his own
medical attendant if he could survive the four or five miles

-journey to the hospital, it was his only chance, and we sent

him in. He was punctured immediately after his admission,
the cerebro-spinal fluid was purulent, and meningococci were
plentiful, both intra- and extra-cellular. He was given 40 c.c.

-of serum. Twelve hours later he was given 20 c.c., but seemed
no better, and the whole cornea in one eye was steamy with
_pus in the anterior chamber. He was given injections daily
for several days and slowly improved. Eventually he re-

‘overed with the loss of one eye. Some patches of skin became

“ necrosed and sloughed. He left hospital after 10 weeks’
‘detention, and lately I heard from his doctor that he now
reports himself in better health than ever before, and he is

earning his living as a carpenter on munitions work. I quote

_this case to show how impossible it is to separate cases which

ft .
‘have no chance ” from other severe cases. If this case had

died, he might readily have been put in the category of cases

which were “‘ hopeless from the first.”
We remained free from the disease in Belfast in 1913, and

to the end of 1914. When there was a reappearance of cases

last winter, I fully expected that we might look forward to
8 _ THE PRACTITIONER.

getting even better results, for, owing to the experience we
had had, the diagnosis was more likely to be made quickly
and, the value of early injection of serum being fully recog-
nized, the cases would most probably be sent into hospital
without delay. It was apparent, too, that we should have
many cases from the camps, and these would generally be in
good physical condition, and at a time of life when good
results were to be expected. But, unfortunately, the results,
instead of being better, have not been so good. Since the
beginning of last winter I have had gz cases in hospital, and
have treated 8 cases in various places outside, making exactly
roo cases. Of these, 36 have died, a case-mortality of 36 per
cent. In the total number we had previously, the death-rate
had been 24 per cent.

In trying to find an explanation of the cause of this
increase several questions occur to one :—

(I) Was the disease of a more virulent type?

(2) Was there any marked difference in the average age’

of the patients, which might make for a higher
mortality ?

(3) Can the increase be accounted for by differences in
the strains of the meningococcus ?

(4) Was the serum available of as high standard of
immunity value ?

(r) Regarding the virulence of the type, it is very
difficult to make a correct estimate, but my opinion is
that the recent outbreak was not more severe in type than
formerly ; although, so far as I have been able to ascertain,
no case occurring in the North of Ireland during the past
winter and spring, which was treated without serum, recovered.
There were several. Unfortunately, the disease is not noti-
fiable in all our sanitary districts, so that it is not possible
to obtain exact figures.

(2) The average age of the patients has been higher in
the recent outbreak. This should, on the results generally
reported in former outbreaks, make rather for a lower case-
mortality, but my own experience has been that young
children give very good results when treated with serum,
provided they come under treatment reasonably early. It is
in the infants that the greatest improvement in results has
been obtained, since the serum treatment became general. In

CEREBRO-SPINAL MENINGITIS. 9

children under one year treated without serum, a death-rate
of go per cent. had been common. With the serum they do
quite as well as cases in other age periods. In the present
outbreak, I have had 17 cases in children under fiv~ ~eors
with only four deaths—less than 25 per cent. One of these
fatal cases had already been over 50 days ill, when admitted

- from a country district 25 miles from the city.

(3) Is the increase in the mortality to be accounted for
by differences in the strain—strains not provided for in the
polyvalent serum available? In the discussion here last
February, I believe that the general impression held by many
of those taking part was that the resistance to the serum
treatment, shown by many of the cases then occurring, was thus
to be accounted for. During the early spring, I had several
cases which were received into hospital quite early in the
attack, but, though living long enough to receive several daily
injections, they showed only very temporary improvement

_or none at all, and ended fatally. I am aware that cases of

this kind have been met with amongst the serum-treated cases
elsewhere ; personally, I had not met with such cases in my
former experience in the use of the serum. My experience
had been that, if a case lived for ten days or a fortnight, it
recovered. In this outbreak that did not hold good I may

“instance one case which occurred amongst my recent cases.

A robust soldier of 20 years was admitted with a severe attack
on the first day of illness; he received repeated injections,
showed some improvement at first but only for a short time.
In all, he was given 15 injections—480 c.c. of serum—and had
over 1,100 c.c. of fluid drained off from the canal He went
steadily downhill, and died after four weeks. The meningo-
coccus was present in the cerebro-spinal fluid till the end. In
my former series, I had not met with such cases. Having had
some correspondence with Dr. Flexner on these resisting cases,
I collected specimen cultures of the organism from cases in
various places, and took them over to New York for comparison
with the strains being used in the preparation of the serum.
Through the kindness of Dr. Martin, I obtained several from
the Lister Institute ; from Dr. Robertson I received some from
Birmingham ; I also received cultures from Professor Beatty’s
laboratory in Liverpool, and from Professor McWeeney, of
Dublin. Most of these I tried to take out in sealed tubes, but
they all died off on the voyage; I had, however, taken a small
ro THE PRACTITIONER.

incubator, and transplanted samples from all these places on
the voyage, so that strains from the various districts were
available for comparison. They showed no marked differ-
ences, when compared with those in use in the preparation of
the serum now being made at the Rockefeller Institute. Some
of them did not agglutinate with the serum in quite so high
dilutions as those in use there, and these have been used in
the preparation of the serum now. With the recent improve-
ments in culture media, interchanges of cultures for comparison
should be less difficult.

(4) Was the serum available of as high a standard of
immunity value? For two or three years before our epidemic
last winter, there had been very little demand for the serum
from the sources of supply in America; then suddenly came
the great demand from this country. Our War Office ordered
large quantities, and much was requisitioned from France,
with the result that the available horses were bled as fre-
quently as possible and the immunity value of the serum
dropped very seriously. For this, and possibly for other
reasons, I think there is no doubt that much of the serum which
reached this country last winter was of a much lower standard
of value than that formerly supplied. J think here lies the true
reason of the somewhat disappointing results sometimes obtained
from its use. Steps have been taken to correct the deficiency
in the quantity and the quality of the serum. Dr. Flexner,
too, has again taken up the preparation of serum at the
Rockefeller Institute, and that now available, judged by
all the laboratory tests, is of higher value than any formerly
in use. I brought back with me a supply of this new serum,
and, so far, I have treated eight acute cases with it. In these
there has been one death. This is very promising, but is
much too small a number to judge by. Some of these
eight cases were comparatively mild, but some were quite
severe types. The latest case, a soldier, admitted nine days
ago, then 24 hours ill, was deeply unconscious with normal
temperature, cyanosis, stertorous breathing, and the dreaded
slow pulse. On puncture, thick syrupy pus was obtained.
He was given 40 c.c. of serum; next day he could be roused,
but had paralysis of one side of the face, and, on the following
day, paralysis of the arm on the same side. He then steadily
improved, and when I saw him yesterday he was quite bright,
the paralysis of face had cleared up, that of the arm nearly so,

CEREBRO-SPINAL MENINGITIS. it

and the meningococcus had disappeared from the fluid. He
appeared on the fair way to rapid recovery. He was given
five injections of serum, 140 c.c.s. in all.*

It would be interesting to have views on the advisability
of taking continuous blood-pressure readings during lumbar
puncture and the injection of the serum, as insisted upon
by Sophian, as well as on the use of general ~~esthetics.
I confess that when I first read Sophian’s note vu the
value of blood-pressure readings, and on the danger of
general anesthetics, I felt uneasy. I had not at that time—
some three years ago—had any cases for a considerable period,
but I felt that possibly the cases I had treated had not got
the best chance; for I had never been guided by blood-pressure
readings, either in fixing the quantity of fluid drained off or in
the dosage, and [ had generally given chloroform.

Early in my experience I received a lesson which I have
not forgotten. I did not like giving chloroform to these

‘patients so frequently, though the patients so often asked for

it. In one of the first cases I ever had—a powerfully-built
man—I had given chloroform at the first injection; when
repeating the injection, I explained to him what I was about
to do, and he consented to bear it without moving if possible.
He allowed me.to puncture him with quite a large trocar

without fuss; the fluid came freely, and all was going well,

when suddenly—I suppose through some slight movement of
the trocar—he felt what was evidently excruciating pair. He
sprang off his side, and made desperate efforts to bury his back

“in the bed, so that I would not again be able to touch the trocar.
; He was immensely muscular ; I had one assistant and a nurse,
“but I was very greatly relieved when I at length succeeded in
getting the trocar removed. I completed the injection under
chloroform. Since then I have always used a general anes-

thetic, unless the patient was unconscious, or in a few cases

‘when there seemed to be some contra-indication. From

my experience of some 800 or 1,000 injections, quite 80 per
cent. of which have been done under general anesthesia, I
believe these patients give no more anxiety to the anesthetist
than any others, and I would recommend the use of a general
anesthetic, unless when obviously unnecessary or for some
reason contra-indicated. I have not been able to obtain suc-

* This case has made a complete recovery.
12 . THE PRACTITIONER.

cess with “‘ water anesthesia,” as recommended by Sophian.

In some cases, I tried taking continuous blood-pressure
readings, but did not think I received any help from them.
With general anesthesia, the variations in pressure do not seem
to be marked either during the withdrawal of fluid or the injec-
tion of the serum. The withdrawal of fluid often gives rise to
very severe pain, and, as Sophian says, the injection at times
gives rise to pain which may be almost unbearable. I think
the explanation of many of the alarming variations in blood-
pressure is to be found in this sudden severe pain set up.
With general anesthesia this is avoided. As the result of his
experience in this method of control of dosage, Sophian
found that much smaller doses of serum appeared to be the
safer course, and recommends that, in young children, the
dose should be 3 to 12 c.c. In my cases in young children,
I have always given the full dose of 20 c.c.—often more—
generally under complete anesthesia, and the results have
been quite good. In the series are included two children
under one year—both recovered. These were not mild
cases. One, aged six months, admitted on the fifth day,
required seven injections, the last on the 19th day; this case
received in all 150 c.c. of serum, viz., six injections of 20 c.c.
and one of 30 c.c.

The best dosage for any age, infant or adult, has not
been as yet worked out. Personally, I am inclined to
give full doses, and to repeat them frequently until definite
improvement is shown. I am quite sure we often use more
serum than is necessary, but at present we have no means of
estimating the risk of withholding it in cases not distinctly
improving.

Though I must confess to some disappointment with the
results in this series of cases, and with the mortality of 36 per
cent., I think there can be no doubt that, should there be a
recrudescence of the disease in this winter, we may look
forward to having available serum of much higher value than
much of that employed in this country last winter.

(c) By H. D. ROLLESTON, M.D., F.R.C.P.

Suvgeon-General (Temp.) Royal Navy ; Senior Physician, St. George’s
Hospital, etc.

From the commencement of the war to July 31st, 1915, there

CEREBRO-SPINAL MENINGITIS. 13

were 170 cases of cerebro-spinal fever in the Royal Nav
The following is a summary of the results of treatment in
163 cases, 89 of which (or 54°6 per cent.) proved fatal :—

 

 

 

 

 

Cases.| Deaths. Recoveries.
Antimeningococcte serum. Per Per
cent.
nanan - - - - | 105 64 or 61°0 | 41 or cent
_ - - - - -| 62 | 43.,, 69-4] 1 30°6
Combined with vaccines, soamin, hex- ° %®
amine, or serum hypodermically -| 43 | 20 ,, 46°5 | 2 53°5
Combined with soamin = - -} 48 | tr, 6Gr'o] 7 ,, 39°0
— » an auto-vaccine - It 2 ,, 18°2 9, 81°8
” » hexamine - - 7 5» 7E°4 1). 2 ,, 28°6
” » serum hypoder - . nat
tically 7 Fw AO) So 74
Hypodermically - .
. . . r 6 . .
Alone - - . - - : I Bre | BS G4
Combined with intrathecal injection °
of serum - - - - - 7 2
Combined with auto-vaccine and °
intrathecal injection of serum : 4 I 3
Combined with an auto-vaccine - 3 2 I
”» » soamin - - I 9 r
Autogenous vaccine (never alone) - - 16 4 OF 25°O | 12 or 75'0
Combined with serum intrathecally - 6 I 5
Combined with serum intrathec I
hypodermically 7 7 * v and 4 I 3
Combined with serum int :
mbined \ : : n athecalty and
Combined with serum hypodermically - 2 2
» soamin - - - T
Soamin - - -
ee - - -| 43 1g or 44°O | 24 or 56°0
te -| 21 7 » 33°3 | 14 ,, 66°
comned with serum intrathecally -| 18 | 11 ,, 6£°0 ; 30°
ombined with serum intrat " °
eee 5s in rathecally and : ' .
Combined with serum i °
ier ‘ m intrathecally and ' '
: * ° . °
Combined with serum hypodermically - x ° i
L ” » auto-vaccine - - I ° :
mbar puncture (alone)
a - - : 13 or 30°8 .
Symptomatic treatment (only) - -| 14 1 7 "4 ; . a6

 

 

 

mo Naturally, the prolonged and unsatisfactory cases received
n . varied treatment than the fulminating ones. Some of
e latter died shortly after arriving at hospital. The most
14 THE PRACTITIONER.

noticeable feature about the tabulated particulars was the
failure of the intrathecal injection of antimeningococcic serum,
though this was obtained from various sources. The cases
treated solely by the intrathecal injection of serum and lumbar
puncture showed a higher death-rate than that of the whole
163 cases. Flexner, in the Journal of Experimental Medicine,
1913, emphasized the importance of injecting antimeningo-
coccic serum intrathecally as early as possible in the disease.
In a table of 1,21r cases, he showed that when the serum
was injected within the first three days, the mortality rate
was 18 per cent.; when between the fourth and seventh
days, 36°5 per cent.; and when later than the seventh day,
36°5 per cent. A comparison on the same lines of the cases
in the Royal Navy showed :

Cases. Deaths. Recoveries.

rst to 3rd day... 70 42 or 60 per cent. 28 or 40 per cent.
4th to 7thday ... 24 14 or 58°4 per cent. to or 41°6 per cent.
Later than 7th day I1 8 or 72°7 per cent. 3 or 27°3 per cent.

The failure of the injected serum to reduce the mortality
clearly was not due to its being given too late. The serum
treatment, which was so successful in the hands of Flexner
and Sophian in America and of Robb in Belfast, was
given a thorough trial in these cases, but proved most
disappointing. Possibly the meningococci were “ fast” to the
action of the serum, or the organisms were para-meningococci.
Alarming symptoms directly after the intrathecal injection
occurred in two cases only, showing that the gravity method
of administration (which was not in vogue in the Royal Navy)
was scarcely necessary when due care was taken. Serum
rashes were noted in 20 per cent. of the cases, but may
have been more frequent; in a few cases, there were also
arthritic pains. No severe anaphylactic symptoms were
recorded, In the 16 cases in which Fleet-Surgeon White-
side, R.N., gave an autogenous vaccine, the low mortality
of 36°7 per cent. was reached. Soamin seemed to give
good results, and to have a beneficial effect in the septi-
cemic stage. Optic atrophy was not noted in any instance,
though in one case 42 gr. were given. Hexamine did not
appear to exert any effect clinically, and was therefore soon
abandoned. Lumbar puncture was performed in 149 of the

CEREBRO-SPINAL MENINGITIS. 15

163 cases, though in 38 once only, but 14 of these died
goon after coming under observation. Six of the other
cases, which had a single tapping, died. Of 22 cases tapped
twice, 8 died. Three tappings were done in 20 cases, with
9. deaths ; 4 in 24 cases, resulting in 15 deaths. Lumbar
puncture, he regarded as a palliative rather than as a
‘cutative measure, by relieving symptoms due to increased
4ntrathecal pressure. In 13 cases, of which four proved
fatal, it was the only form of treatment other than the
‘ordinary symptomatic remedies employed.

“In 14 cases, 10 of which proved fatal, symp* matic

“remedies only (such as morphine for pain) were gi en.

With regard to prophylactic measures, it seen.ed advis-

‘able to invalid the men who recovered from an attack

of the disease, because they might be intermittent or

periodic carriers who alternately gave negative and positive

results on bacteriological examination of throat swabs for
meningococci. Recently, three cases of the disease among
boys were traced to a boy who had recovered from the
disease, and, when examined bacteriologically, was found
to be a carrier.

(@) By MICHAEL G. FOSTER, M.D., Carr. R.A.M.C.

First Eastern Geneval Hospital, Cambridge.

Earty in the epidemic, the Commanding Officer set apart a
ward for the treatment of the disease under discussion, and
cases were collected from practically all over the Eastern
counties and the South Midlands. The first case came under
notice about the middle of January—an officer’s servant, who
was at his work thenight before, and, at 2 a.m., was found in
bed unconscious. He was moved to hospital with the pro-
visional diagnosis of uremia. On arrival, he was profoundly
unconscious, had tremors all over, could not swallow, and

had nystagmus and retention of urine. Only 14 oz. of urine
could be obtained by catheter, and it contained neither sugar

nor albumen. Lumbar puncture yielded an ounce of yellowish

‘fluid containing pus. As the bacteriologist had not made his
-Teport next day, the theca was again punctured, and r} oz. of
fluid drawn off. On the third day, the man was definitely
16 THE PRACTITIONER.

better. The diagnosis being still uncertain, he was again
punctured. The following day he could swallow, and had
recovered consciousness. On the sixth day he was well and
was discharged. On the twentieth day, he returned to duty.
Two other cases occurred within a day or two, from the same
regiment. They also were punctured and both recovered,
but after a somewhat tedious course. The staff then began
to employ serum; six cases were treated with it, and
two were admitted from outside after having received an
injection. Of the eight cases, four died. They concluded
that they were not doing very well with the serum, and,
bearing in mind the good result from simple lumbar puncture
in the first, very acute, case, they treated all the succeeding
cases in that way, repeating it as often as the symptoms
persisted. By the end of March, 28 cases had been treated,
most of them by lumbar puncture. Twenty cases were
treated without serum, and there were four deaths, though
in the next seven cases there were five deaths. About that
date, there seemed to be a peculiarly virulent type of case.
Towards the end of the epidemic, they had a series of nine
cases with only one death. During the time I had charge of
the ward, t.e., to the middle of June, there were 42 cases,
14 deaths,

I submit that frequent drainage of the cerebro-spinal
fluid during the persistence of the symptoms is a satisfac-
tory form of treatment, at all events until a more satis-
factory serum is available than there now seems to be.
The simple procedure resulted in a very striking relief of
symptoms, especially of the very intense headache. A most
important matter was the prevention of hydrocephalus.
Some of the fulminating cases were absolutely unresponsive
to anything. Many cases seemed to recover up to a certain
point, then had a return of severe headache, and relapsed,
ending in death. The onset of hydrocephalus may be marked
by a sudden lapse into an adynamic state with feeble pulse
and unconsciousness. The supervention of these symptoms is
a sign of increased cerebro-spinal pressure, and an indication
for lumbar puncture. Post-mortem, one found that the
_ cord was so tightly bound across that there was no circula-
tion, explaining the impossibility of getting anything from
the cord by puncture. I believe that in many cases daily

CEREBRO-SPINAL MENINGITIS. 17

puncture would prevent hydrocephalus being set up. If
the theca could be kept properly drained, there seemed a
reasonable chance of a successful result. It is a very safe
operation. but I agree with Dr. Robb that it is very difficult
to ensure doing it properly without a general anesthetic. The
greatest quantity of fluid which either my colleague, Captain
Gaskell, or myself has withdrawn is 2 ozs., and no sign of
collapse followed.

(e:) By J. F. GASKELL, M.D., F.R.CP., D.P.H., Ca’ ¢. R.A.M.C.
First Eastern General Hospital, Cambridge.

Tur fifteen fatal cases mentioned by Captain Foster were
all examined post-mortem, and could be divided roughly
into three groups: acuie fatal cases, which did not respond
to treatment and succumbed within five days; sub-acute cases,
dying three to four weeks after onset; and chronic cases,
lasting six weeks or more, which died with hydrocephalus.
In the acute cases, pus was found not merely at the base
of the brain, but distributed all over the vertex in the sub-
arachnoid space round the blood vessels, a most intense
vertical meningitis being present, the whole of the meninges
being greatly engorged. Even in fulminating cases, in which
the disease had lasted less than 48 hours, a considerable
amount of pus was present round the cerebral vessels over
.the vertex. The pathological condition was such that re-
covery from it would seem to be almost out of the question.
Two of the sub-acute cases lasted for about three weeks. At
the post-mortem, a most tenacious, inspissated, purulent exu-
date completely covered the base of the brain, and filled the
sub-arachnoid space of the cord. In contradistinction to
other cases, excess of cerebro-spinal fluid was entirely absent.
Pus was present over the vertex, but in comparatively small
‘amount; the cerebral vessels were not congested. In these
cases, lumbar puncture had been performed repeatedly, but
the amount of pus present, instead of diminishing, had pro-
gressively increased, until finally the fluid became so thick
that it would no longer flow through the largest puncture
needle. After this, only a drachm or two of thin serum
could be-obtained. In one of these cases, serum was used in
an attempt to dilute the pus, but was entirely without effect.
B
18 THE PRACTITIONER.

These cases had initially responded to treatment, but had
finally sunk into an adynamic state. In this class of case,
the purulent infection had apparently paralysed the cerebro-
spinal secretion.

In the chronic group, marked symptoms of hydrocephalus
were present in life, and, post-mortem, the third and fourth
ventricles were found to be widely dilated and filled with
fluid. The lateral ventricles were also, as a rule, distended.
In two cases, the sub-arachnoid space was completely ob-
literated by adhesions in the upper dorsal region. Lumbar
puncture had, therefore, failed to relieve the distension of
the ventricles. In another case, the roof of the fourth
ventricle had become completely adherent to the cerebellum.
In yet another case, no complete obstruction in the cerebro-
spinal circulation was found, but a terminal pneumococcal
septicemia was present.

A common cause of death was respiratory failures the
heart could be kept beating by artificial respiration for some
hours.

The efficacy of daily lumbar puncture, commenced as
early as possible in the illness, was demonstrated in the cases
which had recovered, those punctured on the first or second
day having a comparatively short illness. Some had not
been punctured before the eighth day, and, in these, the ill-
ness had run a very prolonged course. One of these pro-
longed cases had ceased to show further signs of illness after
5 c.c. of his own serum had been injected intrathecally.
This form of treatment was tried, because the agglutinating
power of the man’s own serum had been found to be much
higher than that of any of the artificial immune sera. This
effect may have been merely a coincidence, for other chronic
cases had similarly ceased quite suddenly to show symptoms.
It is, however, intended to test the treatment further.
The net result of the cases at the hospital is a mortality
of 39 per cent., and most of the cases were treated by lumbar
puncture, unsupplemented by any other form of treatment.
I contend that the details of the cases showed up as
well under that simple procedure as other series in which
lumbar puncture and the injection of serum had been carried
out,

ee 6