REVIEW ARTICLE

SPECIAL

SECTIONS

REVIEW

ARTICLE

ACUTE

BACTERIAL

MENINGITIS

By Margaret H. D. Smith, M.D.

blanc University School of Medicine and Charity Hospital, New Orleans, Louisiano

PRESENT ADDRESS: Department of Pediatrics, New York University College of Medicine, 550 First

Avenue, New York, New York.

258

Ped

#{237}a!

rics

VOLUME 17 FEBRUARY 1956 NUMBER 2

cum menmgitis is an entity which

arouses the interest of most

practi-tioners of medicine as well as of the bay

public. Formerly it was exciting mainly

be-cause of the dramatic onset and death or

sequebae which occurred in so many

pa-tients; now we have the added incentive of the excellent results of treatment in cases

where tile diagnosis is made reasonably

early.

One curious thing about meningitis is that

it belongs entirely to the domain of the

clinician, with help only from the

bacteri-ologist. All of our knowledge about

meningi-tis is based on observations made in man. In

many diseases, such as rabies,

poliomyeli-tis, bobar pneumonia, a large part of our

knowledge is based upon animal

experi-mentation. Not so with meningitis. As a

matter of fact, the experiments on animals

carried out by Weed,1 Wollstein,2 and others

between 1915 and 1925 contributed

disap-pointingly little to our understanding of the

pathogenesis of this disease. Animals are

apparently just not susceptible to meningitis

in nature. Perhaps the reason is to be sought in the far larger size of the brain in human

beings with the relatively greater blood

supply to this organ. If the average adult

brain is perfused with something like 800

ml. of blood per minute,3 and the child’s

brain with almost as much, then tilere is

ob-viously ample opportunity for whatever

bac-teria are in the blood to set up infection in

and around the cerebral blood vessels,

spe-cially the smaller ones, many of which lie

in the meninges.

Meningitis has really only relatively

re-cently been recognized. Vieusseux4 in

Swit-zerland and North5 in this country described

epidemics of meningococcal disease in the

early Nineteenth Century, but it was the

German internist Quincke6 who put

infec-tion of the central nervous system “on the

map” by perfecting the technique for lumbar

puncture and then correlating the evidence

which he obtained on lumbar puncture with

what he found clinically. In a monograph in

1893 he differentiated serous and purulent

meningitis, gave minute details of the

tech-nique of lumbar puncture, which by that

time he had carried out 40 times; he also

pointed out that increased intracranial pres-sure, rather than increased fluid per Se, was

respollsibbe for brain damage; and finally

If we compare our present day experience an infectious agent is involved affects much

more severely the convexity of the brain

than the ventricles. He advanced the

ex-traordinarily modern concept that the para-site, as he called it, reaches the brain via the

bloodstream, and pointed out that the

con-vexity of the brain has a tremendous blood

supply.

Somewhere along the way, in the course

of studies on meningitis, around the time

of the first World War, the idea became

current that bacterial meningitis is usually

produced by invaders travelling back from

the sinuses and nasopharynx along nervous

and venous pathways to the subarachnoid

space. This theory has now largely been

abandoned, and we believe that almost all

cases of meningitis, of whatever etiology

(except tubercubous) are secondary to blood

stream infection. There are undoubtedly a

few exceptions, where meningitis arises as

a result of direct trauma to the skull and

dura, of fractures through the sinuses, or

of abscesses in adjacent areas.

Meningitis was studied a great deal from

1905 on, both in this country and in France and Germany, in efforts to learn the nature

of infecting agents and to perfect specific

antisera. In 1910 the New York City

De-partment of Health under Dr. W. H. Park

even established a special Meningitis

Divi-sion, which, through its clinical and

bac-teriologic investigations, contributed a great deal to our knowledge.

ETIOLOGY, AGE, SEASONAL INCIDENCE

From the studies of Neal,7 Fothergibb and

Sweet8 it became clear that more cases of

meningitis occur in the first year of life

than in any other year. This holds true now9 as then, for all the common types of

menin-gitis except tubercubous meningitis, which

is commoner during the second year of life.

The studies of Fothergill and Wright’0 made

clear that the reason for this bay in the lack

of immunity of the small infant. They

showed in 1933 that actually the number of

cases of Hemophibus influenzae meningitis was inversely proportional to the

bacteri-cidal power of the blood for this organism.

During the first 2 months of life, when the

infant has received bactericidal substances for H. influenzae by passive transfer, cases

of H. influenzae meningitis rarely occur.

They are frequent during the time when the

average titer of protective antibody is low,

and the incidence drops off as the antibody

titer reaches adult levels, around the age of

7 years. That a similar pattern prevails in

the case of the pneumococcus was clearly

demonstrated by Sutliffe and Finland.”

Antipneumococcab antibody in the newborn

parallels that of the mother, that is, it is

present against many types. It is lost by the

end of 3 to 5 weeks and is not again present

in appreciable titer until after the first

year. The age incidence of pneumococcab

meningitis, is, as might be expected,

in-versely proportional to the average titer of

antibodies against Diplococcus

pneu-moniae.”

In meningococcal meningitis the age

in-cidence is essentially similar, most of the

cases and most of the deaths from this

dis-ease occurring in the younger age group, as

clearly illustrated by the great Chilean

epidemic of 194143.13 The incidence curve

however never falls so low as is the case

with pneumococcal meningitis. Since many

adults are apparently not immune, it follows

that many newborns do not inherit

im-munity either, so that meningococcab menin-gitis in very young infants is not a rarity.14

In interepidemic years the incidence of

meningococcal meningitis is second only to

that of H. influenzae meningitis. About

once every 8 to 10 years meningococcal

in-fections prevail in epidemic form and are

responsible for more cases of meningitis

than all other agents.

A curious fact of some interest is the

seasonal pattern followed by different types

of infection. Rivers” showed in 1922 that

H. influenzae infections occur mainly in

the autumn and early winter. The

menin-gococcus and pneumococcus on the other

hand are apparently at their most vicious

in the early spring. This pattern holds

clearly for the semitropical climate of New

Orleans as it does in Baltimore and New

TABLE I

CLINICAL MANIFESTATIONS OF MENINGITIS

Newborn cyanosis

fever

vomiting

jaundice

irregular breathing

jitteriness or drowsines4

Older infant

fever

vomiting

jitteriness or drowsiness

convulsions

bulging fontanelle

Children over 2 years

fever

drowsiness

headache

stiff neck

vomiting convulsioiis

260

as to etiology of meningitis,9 we find that

our experience differs from that of 30 years

ago; we see many fewer patients with

tubercubous meningitis, very few patients

with streptococcal meningitis and relatively

more patients with infections due to

Gram-negative bacilli, particularly H. influenzae. It is noteworthy also that Salmonella

menin-gitis is practically never mentioned in the

older literature; yet today Salmonella

meningitis, while by on means common, is

seen from time to time on every large

serv-ice.9’17 This is probably a reflection of the increased incidence of Salmonella infections of all sorts, owing to our increased national

consumption of meat, poultry and eggs.

Meningitis in the premature and newborn

deserves special mention with respect to

causal agent. The premature and newborn,

though temporarily protected to some

de-gree against H. influenzae and D.

pneu-moniae, is exposed to other special bacterial

hazards. Several studies have shown that

the flora of the skin, of the umbilicus, of

the eye and the oronasal cavity in

new-19 is the same as that of the birth

canal,’#{176}consisting mainly of Escherichia coli

and other gram-negative bacilli, green

streptococci and staphylococci. These are

the organisms which have long been known

to give rise on occasion to sepsis and menin-gitis in this very youngest age group.2’

Kagan,22 in a study on meningitis in

pre-matures, found that of 22 such patients

14 had meningitis due to E. coli or

Klebsi-elba.

CLINICAL MANIFESTATIONS

The symptoms and signs of meningitis

are those found in any febrile disease (fever,

nausea, drowsiness) plus the manifestations

of increased intracranial pressure and cere-bral irritation (splitting headaches,

convul-sions, stiff neck). The trouble is that the

“typical patient” with headache, stiff neck

and Kernig’s and Brudzinski’s signs is over

the age of 2 or 3 years, whereas a majority

of the cases occur in younger infants. The

premature, the newborn and even the older

infant with meningitis display a much less

characteristic picture,2’ probably because

NB.: The younger the patient, the more vague the syinptons.

the skull is expansible at this age, so that

the usual indications of increased

intra-cranial pressure are often not apparent. In

the very sn-wi! infant (premature or

new-born) cyanosis, fever, vomiting, jaundice, ir-regular breathing, perhaps unusual jitteri-ness or drowsiness, are the signs which point to meningitis.22 Convulsions, nuchal rigidity

and tenseness of the fontanelbe often appear late or not at all. In infants of 2 or 3 months

or more, fever is almost always present, as

webb as vomiting, jitteriness or drowsiness

(sometimes these two alternate), bulging

fontanelle and a high-pitched cry. In this

age group a presumptive sign of central

nervous system disease which may be very

useful is the tache c#{233}r#{233}brale:when the skin

is stroked with the fingernail or other

blunt object, a red line appears and persists

for some minutes.

In Table I are set forth for comparison

and contrast the early clinical manifestations

of meningitis as they are seen in each age

group. Beyond the age of 2 or 3 years, the

child with meningitis displays signs and

though restlessness is rarely so pronounced

as in the adult.

Convulsions are by no means always

present, but are frequently enough

associ-ated with the onset of meningitis, so that

it is an excellent rube always to perform

a lumbar puncture in every patient with

so-called febrile convulsions.

Cranial nerve palsies always suggest the

possibility of meningitis, but are not in any

way specific, with one exception. In our

experience paralysis of the third nerve is

associated with tubercubous meningitis in

infants, never with acute pyogenic

menin-gitis.

The optic discs should always be booked

at in patients suspected of meningitis, first

because it is always good practice before

performing a lumbar puncture, but also for

the evidence which it occasionally sheds

on the disease process: if the patient shows

real papilledema, then he does not have

un-complicated acute pyogenic meningitis.

Ap-parently papibledema in addition to other

manifestations of meningitis should

im-mediately bead one to consider tuberculous

menmgitis, or perhaps an intracranial

ab-scess with secondary meningitis, or septic

sinus thrombosis.

Careful examination of patients suspected

of meningitis often reveals useful bits of

evidence other than those already

men-tioned. Any signs pointing to sepsis: in the

newborn, jaundice and infection of the

urn-bilicus; in the older infant a hot swollen

joint, particularly one of the small joints

of the hands or feet, may be associated with

invasion of the bloodstream by Neisseria

meningitidis or H. influenzae-and in a

patient of any age a petechial or purpuric

rash points to meningococcemia, although

identical rashes occasionally occur with

pneumococcus’4 or H. influenzae.’’25

Another useful clinical point to which one

should pay attention is the presence of any

dimple, nevus or small opening anywhere

along the midline over the spine or the back

of the head. Such marks may be the only

clue to the presence of a congenital dermal

sinus which may communicate directly with

the subarachnoid space, or even lead

di-rectby from the outside into the central

ependymal canal. Such a sinus may remain

asyrnptomatic for months or years, although

most of them become clinically manifest

before the age of 5 years because of their

tendency to become infected, usually with

a cobiform bacillus.2628 It is essential to

diagnose this type of infection correctly,

be-cause, although meningitis secondary to

such a sinus may clear up on antibiotic

ther-apy, it will recur, once the sinus has been

infected, until the sinus has been

com-pletely removed surgically. The prognosis,

even with extensive sinuses extending up

the cord, is excellent.

And finally, one should also be sure that

there is no swelling or tenderness over the

spine or just lateral to it, such as is seen rather often with epidural abscesses. These

are more common in older children and

usually follow trauma. Since in an epidural

abscess the pus usually lies dorsal to the

subarachnoid space, it is theoretically

pos-sible, if the diagnosis is overbooked, to go

right through the abscess in doing a

diag-nostic spinal tap and carry organisms from

the abscess into the previously uninfected subarachnoid space.

There are other features of the patient’s

appearance and his history which may give

valuable leads as to the etiology of his

dis-ease. Purulent conjunctivitis is not

uncom-monly the forerunner and perhaps the

portal of entry for any of the common

meningeal pathogens in infants. A draining

ear, particularly if it has been present for

2 or 3 weeks, suggests the likelihood of

pneumococcal meningitis: sometimes a

stained smear of the drainage will reveal

pneumococci and permit a quick

presump-tive diagnosis. Anemia, for some

unex-plained reason, accompanies about half

the cases of H. influenzae meningitis,24’29

and develops so rapidly that it is often

noticeable when the patient is first seen.

Damage to the skull, either recent or

re-mote, and skull defects have been a

promi-nent etiologic factor in pneumococcal

men-ingitis in the experience of some,’#{176}though

we ourselves have not been impressed by

262

DIAGNOSIS

Early detection of meningitis, accurate

diagnosis and appropriate treatment are of

the essence if one is to do the best by

pa-tients with meningitis. The only really good

way to proceed seems to be to have a very

high index of suspicion, particularly in

young patients, and then immediately to

do a diagnostic lumbar puncture. This

would entail doing a number of lumbar

punctures on patients who have

menin-gismus secondary to penoumonia,

osteo-myebitis and other infections. The question

then arises as to whether lumbar puncture itself is an innocuous procedure, especially

in the presence of bacteremia. In

experi-mental animals, withdrawal of spinal fluid

seems to predispose to meningitis when

meningococci or pneumococci are

intro-duced simultaneously into the bloodstream. Pray,” in 1941, made a careful statistical

analysis of the records of 4 large pediatric

services. He was entirely unable to find any

evidence that lumbar puncture in cases of

pneumococcal bacteremia increases the

chance of meningitis.

Lumbar puncture should be carried out

at the slightest suspicion of meningitis. The

only serious contraindication is

papil-bedema: this is rare in meningitis and occurs

in our experience only with tubercubous

meningitis, or when meningitis arises in

conjunction with an intracranial abscess.

Under these conditions one may still be

forced to do a lumbar puncture for

diag-nostic purposes, but no more than 1 or 2

ml. of cerebrospinal fluid should be

re-moved. If the patient shows fresh petechial

or purpuric lesions on the skin, a carefully prepared slide from such a lesion will often

show abundant meningococci and obviate

the need for lumbar puncture: that

organ-isms can be found in 85 per cent of petechial

smears has been demonstrated

repeated-ly.24’32 Petechiae or purpura may however

occur, though rarely, with Hemophibus and

Pneumococcus infections, so that the skin

lesions alone, in the absence of

confirma-tion by the laboratory, do not constitute

TABLE II

DIAGNOSIS OF MENINGITIS

Clinical

Note: state of consciousness

presence of rash presence of swollen joints

signs of shock (cold, clammy extremities, etc.)

blood pressure bulging fontanelle stiff neck

Kernig’s and Brudziiski’s signs

tache c#{233}r#{233}brale cranial nerve palsies

Laboratory

1. examination of CSF

smear

glucose determination

cell count: total and differential

. blood leukocyte and hemoglobin deterniiiiat ions 3. blood culture

4. smears of any ear or eye discharge

N. B.: All diagnostic and therapeutic procedures

should be carried out quickly, with as little disturbance

to the patient as possible.

absolute evidence of meningococcal

infec-tion.

When a lumbar puncture is performed,

preparations should be made to obtain all

possible evidence without having to repeat

the tap in the near future. If the patient is

being tapped at home, or in a small

hos-pital, with the possibility of having to

trans-fer him elsewhere for treatment, an extra

tube of spinal fluid, sterile if possible,

should be saved to send to that hospital

along with the patient. The pressure should

be measured if possible. Experimental

studies on the physiology of the cerebral

circulation show that when the intracranial

pressure exceeds 400 to 500 mm. of water,

cerebral anoxia is inevitable. Such high

cerebrospinal fluid pressures are more

fre-quently a problem in adolescents and young

adults than in small infants; they are often

associated with great restlessness and

thrashing on the part of the patient.

Examination of Spinal Fluid

The most important determinations to

REVIEW ARTICLE

importance, a stained smear, a culture, and

a sugar determination. Measurement of

pro-tein is particularly useful if the spinal fluid is clear, or almost so, as in the first hours of

infection, or during convalescence.

Meas-urement of chloride serves no useful

pur-pose : since the spinal fluid level reflects the 1)lOOd chloride bevel, it is apt to be low in

diseases accompanied by dehydration, like

tuberculous meningitis, but there is nothing

specific about it.”

A. Sx1Eis. Since the smear yields more

information than any other test, it should be

carried out immediately by the most

corn-petent person available. Smears are

particu-larly important in these days when so many

of our patients have already received

sul-fonamides or antibiotics before we see

them, with resulting spinal fluid drug levels adequate to inhibit growth of the organism

in vitro without being adequate to stop the

disease in vivo. One of the pitfalls in

ex-amining spinal fluid smears is heating the

slide too hot when fixing: this coagulates

tile leukocytes and makes the formed

ele-ments difficult to stain. Drying with

com-pressed air alone, when available, is the

ideal fixative for smears. Staining by Gram’s

method is often unreliable; we greatly

pre-fer methylene blue or even Wright’s stain,

with reliance on morphology of the

organ-ism rather than on color. Given a properly

prepared slide from a patient with

menin-gitis the physician or technician can

al-most always, though sometimes only after

a long search, find the causative organism;

this is particularly true in influenzal and

pneumococcal meningitis. In examining a

smear it is worthwhile, as an aid in

prog-nosis, to note the relative proportion of

leu-kocytes and bacteria, also the presence or

absence of phagocytosis: the presence of

dozens or hundreds of microorganisms per

leukocyte denotes a poor defense response

on the part of the patient, as does also the

absence of phagocytosis.

B. CULTURE. The spinal fluid for culture

should be inoculated onto suitable media

(preferably prewarmed to incubator

tem-perature) as quickly as possible. Agar plates

or slants prepared with rabbit’s blood are

much more satisfactory than those which

incorporate human blood (perhaps because

of the antibodies in the batter). Every spinal

fluid should be inoculated into a biquid

medium as well: spinal fluids containing

large numbers of leukocytes often do not

grow well on agar. If sufficient spinal fluid is available, a small tube of the spinal fluid

itself, incubated with addition of a few

drops of sterile 5 or 10 per cent glucose

solution, may yield growth where cultures

on artificial media fail.

C. CELL COUNT. The cell count is not by itself of great importance, but it is useful to

know that a sharp rise in the total number

of spinal fluid leukocytes often occurs as

improvement sets in. Sometimes this rise

on the second day leads to the erroneous

conclusion that the infection is becoming more serious.

D. GLUCOSE. Like examination of the

smear, the glucose determination should

and can be carried out immediately with

a minimum of effort, and yields very useful information. The “six-tube test,” originally

developed at Boston Children’s Hospital,

is extremely reliable when carried out

ac-cording to the directions given by

Alex-ander.340 That the spinal fluid glucose falls

in bacterial meningitis has been know for

many years: Goldring and Harford,” in an

experimental study on dogs with aseptic

meningitis, concluded that “consumption of

glucose by beukocytes and bacteria does not

appear to account for lowered levels of

glucose in bacterial meningitis”; others

dis-agree with them.” Leukocytes do

metab-olize glucose in vitro; nevertheless the large numbers of leukocytes present in the spinal

fluid of patients with equine

encephalomye-litis fail to bower the sugar.24’3’ Whatever the mechanism, lowering of the spinal fluid

glucose below its normal value of about

35 mg./100 ml. is the most delicate

indica-* We have found interpretation easier if the

Benedict’s solution is overlayered with spinal fluid,

rather than mixed, and if the tubes are allowed

tion of the presence of live bacteria in tile subarachnoid space. The spinal fluid glucose

often returns to a normal value while the

leukocyte count is still rising. Sharp

atten-tion should be paid to determining the

spinal fluid glucose whenever the diagnosis

of meningitis is entertained, and whenever the progress of a patient with known menin-gitis is to be evaluated. Occasionally, within

the first few hours of onset of the disease,

the spinal fluid glucose content may still

lie within the normal range; this is more

often the case in pneumococcal and

menin-gococcal infections than in those due to H.

influenzae.

Other Useful Laboratory Procedures

A blood culture should always be

per-formed on every patient with meningitis,

since the etiobogic agent can sometimes be

recovered from the blood when the spinal

fluid culture is sterile.

The leukocyte count yields valuable

in-formation. A leukocyte count of 8000 or

be-low has, in our experience, been a poor

prognostic sign.. We have thought that

transfusions of fresh whole blood helped

some patients with overwhelming infections and a low leukocyte count, but this is purely

a clinical “feeling.” The eosinophil count

may also be of value.

TREATMENT

The sulfonamide drugs and antibiotic

agents are so revolutionizing the treatment

of patients with meningitis, that whatever

recommendations are made this year will

probably be out of date by next year. We

all know, however, that while a great deal

of attention must be devoted to the proper

choice and administration of antibiotics, a

number of other factors are enormously

im-portant in assuring the patient’s recovery;

and these will no doubt always remain

im-portant. They are in fact so essential, that

they undoubtedly account for some of the

discrepancies in mortality rates between

case series from different hospitals.

Of these “nonspecific” factors, we believe

that single most important one to be

promptness of diagnosis and early treat-inent. A delay of a single hour may make

a decisive difference in the course of an

infant with sepsis and meningitis.

Next in importance is rest. Patients with

meningitis tolerate handling and noise very

poorly. All diagnostic and therapeutic

pro-cedures should be carried out expeditiously,

with as little disturbance to the patient as

humanly possible: he should not be

sub-jected to repeated physical examinations on

the first day in the hospital; one venipunc-ture should suffice to obtain blood for count

and culture, and to inject the necessary

intravenous drugs, etc. Extreme restlessness

on the part of the patient himself is also

to be avoided. The safest sedatives are

intra-muscular paraldehyde (0.2 ml. of a 5 per

cent solution per kg. of body weight

in-jected into the lateral aspect of the thigh, or suspended in oil and instilled into the

rec-tum) and/or the less prompt-acting chboral

hydrate (0.2 ml. per kg. of a 10 per cent

solution by mouth, by stomach tube or by

rectum, not over 10 ml.). For prompt

con-trol of convulsions, a few whiffs of

chloro-form given together with oxygen (or, when

a tank of oxygen is not available, hold the

chloroform-soaked pledget of cotton well

away from the patient’s face to avoid

anoxia!) usually produce almost

instantane-ous results. Barbiturates in all forms and

particularly opiates depress respiration and

should be avoided.

Adequate fluid intake is as important to

the welfare of patients with meningitis as

to others, particularly if the patient is

re-ceiving sulfonamides. However we do not

feel that all patients with meningitis should

receive intravenous fluids, just because of

the diagnosis of meningitis: rather,

par-enteral administration of fluids should be

reserved for those who show evidence of

circulatory collapse or definite dehydration. Otherwise oral fluids are far more

satisfac-tory, particularly carbonated beverages.

For unconscious patients, a polyethylene

catheter passed through the nose into the

stomach permits administration of both

TABLE III

GUIDE TO TREATMENT OF MENINGITIS IN CHILDREN

Drug Dose

N. ineningitidis stilfliziiie (mneningococcus)

48 hours

ill. or sbc.: iv.: i.In.: iv.:

i.iii.: i.thec.: ill,.:

E. coli

I1)kIIO%V11

1’tiologu

Agent

Usual Time fcr S1opping Treatment

I-I. influenzae chloraniphenicol (Pfeiffer bacillus)

1) pneumoniae penicillin (aqueous)

(pneuniocoerus)

sulfadiazine Ps. aerugillosa polyniyxin B

streptomycin sulfadiazine chloramphellicol penicillin chloraniphenicol sulfadiazirie

oral: 100 mg/kg. initial (= I gr/ll).)

50-100 mg./kg./24 hr. ill 3-4 (loses (= 4-I grub.)

i.m.: 60-100 mg./kg./24 hr. in 2-3 doses iv.: 60-100 ing./kg./24 hr. in 2-3 doses oral: 100 mg/kg. initial

(= Igrub.)

200 Ing./kg./24 hr. in 3-4 (loses (=14 gr./lh.)

100 ing./kg./24 hr. ill 2-3 (loSes

50 111g./kg.

up to 1,000,000 u. q. 6-8 hr.

up to 1,000,000 u. q. 6-8 hr. ILS above

2.5 rng./kg./24 hr. for 4days

1-4 (loses of 2-5 111g.

50 mg/kg. daily

as above

115 al)ove as above as above as above

5-7 days if CSF sugar

normal and culture

Ilegative

I week after telllpera-ture and CSF are

normal

I week after

tempera-ture and CSF are

normal

5-7 days if (‘SF sugar is normal

In infants fluid and formula intake are

often facilitated if the patient is allowed to

remain lying in the crib: if he is picked up

in the nurse’s arms, pain in the neck and

back may interfere with his appetite.

Specific Therapy: General Considerations

All patients should have an initial

lum-bar puncture, with every effort made to

identify the etiobogic agent and treat

ac-cordingly. The practice of giving 4 or 5

drugs at random is to be deplored: 1)

be-cause the patient already maybe or may

become sensitive to one or more of these

drugs (sensitivity to penicillin is the leading

cause of anaphylaxis in this country today!);

2) because in giving 4 or 5 drugs one may

omit the very one which would cure the

disease (e.g., an infant admitted last year

to Charity Hospital with spinal fluid

cul-tures positive for H. influenzae despite prior

treatment with sulfadiazine, penicillin,

streptomycin, aureomycin#{174} and

terramy-cm#{174}; he recovered rapidly with

chbor-amphenicol alone!), or 3) because the

un-necessary use of antibiotics is expensive,

time-consuming for the nursing staff, often

keeps the patient awake when he needs

rest, and causes pain, gastrointestinal

dis-comfort, local abscess, secondary infections,

etc.

Specific Therapy: Meningitis Due to

H. lnfluenzae

The ability to cure almost all cases of H.

influenzae meningitis is among the great

privileges accorded to physicians today, as

opposed to theIr forebears who prior to

1938 witnessed only rare recoveries.’5 In

1938 Hattie Alexander succeeded in

pro-ducing specific rabbit antiserum of high

titer against type b, which is responsible for 95 per cent of all cases. The use of this

266 SMITH ACUTE BACTERIAL MENINGITIS

the sulfonamides resulted in a dramatic

change in the recovery rate, from 1 per cent to 90 per cent or better. However, the

treat-Illent was tedious, very expensive and often

accompanied by serum reactions, and is

now, in our opinion, of historic interest only.

Each new antibiotic as it appeared was

eagerly tested. Streptomycin was efficacious;

it worked best when at least a small part

of the total dose was given intrathecally, a

definite drawback. Because of the rapid

emergence of streptomycin-resistant

organ-isms, sulfadiazine was given concurrently.

Even more serious was the frequency of

vestibubar dysfunction and other

neuro-toxic effects as a result of treatment, even

when streptomycin administration was

con-tinued for only 24 hours. Although some

clinicians obtained good results with

streptomycin and sulfadiazine therapy and

were well satisfied,3#{176} many others,

includ-ing some of the original proponents of

streptomycin, were eager for a drug with

less serious toxic potentialities.

Aureomycin#{174} and Chloromycetin#{174} soon

came under trial. Studies on in-vitro action

against H. influenzae showed both drugs to

be rapidly bactericidal.37 Clinical compari-son of the rates of appearance in the spinal fluid are in favor of chboramphenicol.38 It is

not surprising therefore that, while many

patients treated with aureomycin recovered, some showed positive spinal fluid cultures

for several days.39’4#{176} Terramycin#{174}, while

slightly better absorbed into the spinal fluid

than aureomycin, is inferior in this respect

to chloramphenicol.4’

Chloramphenicol can readily be

admin-istered by mouth or by stomach tube. To

mask its bitter taste, we have found the best

vehicles to be honey or pur#{233}ed fruit,

espe-cially pur#{233}ed apricots, or canned apricot

“nectar.” Recommended dosage varies from

40 to 200 mg./kg. as an ibitial dose, with

maintenance doses given at 6-, 8-, or

12-hour intervals. Our own practice has been

to give 100 mg./kg. as an initial dose,

fol-lowed by 250 mg. every 6 or 8 hours,

de-pending on the size of the child. We suspect the initial doses in the lower range may take

longer to produce effective spinal fluid

levels. Intramuscular chboramphenicol in

doses of 40 to 50 mg./kg. every 8 to 12

hours, or intravenous chioramphenicob in

doses of 15 mg./kg. every 6 hours have been

found 342 Rectal

administra-lion cannot be relied on at all and should

never be 3 Some patients have

done poorly when chloramphenicol was

given in the form of the palmitate ester:

blood and spinal fluid bevels achieved with

Chioromycetin palmitate#{174} are both lower

and more slowly attained than with

crystal-line chboramphenicol.4’ Woodward’s group

has been satisfied with chboromycetin

palmi-tate,44 but it should be emphasized that in

their patients the initial dose of the drug

was given mntravenousby, and this may be

responsible for their good results.

In recent years aplastic anemia has been

reported following the use of

chborampheni-co!.45 None has been seen at Charity

Hos-pital in New Orleans, despite a very large

experience with the drug. Nor has it been

possible to produce anemia experimentally

in monkeys, even with large doses given

daily for 15 months.6 Since, in the

re-ported cases, anemia usually followed

pro-longed or repeated administration of the

drug, it seems wise to reserve the use of

chloramphenicol for serious illnesses where

it is known to be particularly efficacious:

there is no powerful therapeutic agent

known to man which is not responsible for

occasional, serious accidents. “The circum-stantial evidence of a possible relationship

between aplastic anemia and

chlorampheni-col calls for clear indications for the use

of this antibiotic, but its great assets merit respect.”47

With the use of chiorampenicol either

alone or in conjunction with sulfadiazine, the mortality from H. influenzae meningitis has fallen to 10 per cent or below.16’ 4850

Specific Therapy: Meningitis Due to

N. Meningitidis

Meningococcal meningitis is, after H.

influenzae meningitis, the most frequent

the commonest l)y far during tile epidemics

wIlicIl come every 8 to 10 years. Despite the

newer antibiotics, no drug is so efficacious

as the sulfonamides. Sulfadiazine

(sub-famerazine and sulfapyridine are equably

good) should be given intravenously

im-mediteby when the diagnosis of

meningococ-cal infection is made or even seriously

sus-pected, and should be followed up by oral

or subcutaneous administration of

sulfona-mides. Meningococci are apparently so

susceptible to the sulfonamides that dosage is relatively unimportant. Nor has the

emer-gence of sulfonamide resistance ever been

convincingly demonstrated.’1 As to the

dura-lion of treatment, it can afford to be very

much shorter than with other types of

meningitis. We ourselves, in a very large

series of patients with this disease seen in

Baltimore some years ago, obtained

excel-lent results by giving one intravenous dose

of the drug, followed by several oral doses

for a total of only 48 hours. That even 1

single intravenous dose of sulfadiazine is

sufficient to cure the disease was shown in

a small series of patients.’2 It is true that

the patient very often still suffers from

head-ache, stiff neck, sometimes fever and

al-ways pbeocytosis for longer than 48

hours-the absorption of the meningeal exudate

takes time-but it is not possible to recover

N. meningitidis from tile spinal fluid within a few hours of giving intravenous

sulfona-mides. There is no tendency to abscess

formation in meningococcal disease, nor do

relapses occur after sulfonamide therapy.

Other antibiotics such as Aureomycin#{174},

Terramycin, and chboramphenicob,” have

been followed by cure in meningococcal

meningitis, but it seems that, with the first

2 drugs at beast, recovery is often delayed.

With penicillin alone this delay is rather

prolonged, so that penicillin therapy by

it-self does not constitute optimal therapy

for meningococcal meningitis.’4

Specific Therapy: Meningitis Due to D. Pneumoniae

Pnetimococcab meningitis is the most

diffi-cult of the common types of meningitis to

treat. The onset in children is often sudden, contrary to H. influenzae meningitis, where

the onset often cannot be dated with

cer-tainty. Sometimes it is associated with an

ear or an eye infection, sometimes with

pneumonia; frequently these warning signs

are lacking. Too often the picture is that of

an infant with an overwhelming infection of

same sort, but without particular signs of

meningeal irritation. By the time the

diag-nosis is established, the disease process is

already far advanced, and the outlook

cor-respondingly dim. In children over the age

of 2 to 3 years, as in young adults, the

out-look is less serious.

Peniciblin with or without the addition of

sulfonamides has for some years now been

considered in most clinics the best available

treatment for pneumococcai meningitis.

When penicillin was first made available,

several investigators showed that even in

the presence of inflammation of meninges,

penicillin, in the dosage then in current use, did not appear in high concentrations in the spinal fluid. Thus the success of treatment

at that time may have been due in

consid-erable measure to the rapid diffusion of the sulfonamide drugs which alone are sufficient to cure almost half of the cases.’5 Conclusive

studies soon showed, however, that

follow-ing intravenous or intramuscular doses of

20,000 to 40,000 units, penicillin rapidly ap-peared in the spinal fluid in concentrations

bactericidal for the usual pathogens.’#{176} For a number of years thereafter patients

with pneumococcal meningitis were treated

in different clinics with various

combina-tions of penicillin intravenously,

intra-muscularly, intrathecabiy, with or

with-out sulfonamides. There are probably few

diseases susceptible to treatment by drugs

in which the reported results of treatment vary so widely. In 1 reported series5T there

were 81 deaths among 102 patients, in

an-other, 3 deaths among 35 patients.’8 In

analyzing the results of several groups of

patients,576#{176} the following facts stand out: 1) there is a higher mortality among patients

above 40 or 50 years than among children;

268 SMITH ACUTE BACTERIAL MENINGITIS

administration, i.e., whether intratheca! or

IlOt, do Ilot appear to matter. Lowrey and

Quilbigan,#{176} with 3 deaths among 18

pa-tients, used no intrathecal penicillin; Ross and Burke,#{176}2 with 3 deaths among 19

pa-tients, include intrathecal penicillin in their

regime, so also does McKendrick,58 whose

record of 3 deaths among 35 patients of

all ages stands as a goal for others

to emulate. Nemir and Israel,65 in review-ing all of the recent reports in the literature

of pneumococcal meningitis among

chil-dren, conclude that “intratheca! penicillin

is not a necessity.” Still pertinent is the

reasoning that “there is a lack of convincing evidence that the introduction of penicillin

into the subarachnoid space increases the

concentration of the antibiotic in the

menin-geal tissues. All layers of this tissue are

richly supplied with blood vessels... . Since

the infection is one involving the meninges,

it would seem logical that the purpose of

treatment would be to maintain a high

con-centration of the therapeutic agent in the

tissues and not in the exudate. This can best

be effected by adequate blood levels.”6’

In an attempt to provide extremely high

blood bevels of penicillin, Dowling and his

associates67 recommended a million units

of penicillin intramuscularly at 2-hour

in-tervals. Unfortunately, of their 21 patients

treated in this fashion, 8 died (38 per cent) so that their results are unconvincing.

Aureomycin#{174}, chioramphenicol and

Ter-ramycin#{174} have all in turn been tried in

pneumococcal meningitis, usually in

con-junction with penicillin; suffice it to say that

recoveries have been reported with the use

of each, but that only small numbers of

patients are included.44’ 68

Combined treatment using penicillin and

aureomycin is discussed by Lepper and

Dowling69 in a much quoted paper: “Of 43

patients treated with massive doses of

par-enteral penicillin, 13 (30 per cent) died.

Among 14 similar patients treated with

aureomycin in addition to the same dose of

penicillin, 11, or 79 per cent died.” They

“favor the conclusion that penicillin and

aureomycin are mutually antagonistic when

employed together in the treatment of

pneumococcic meningitis.” However the

patients tinder treatment did not alternate

in regular fashion, which introduces

un-known factors. Also their results varied

greatly in different age groups : actually, 3

of the 11 children treated with penicillin alone died, whereas the 2 treated with both

penicillin and aureomycin survived!

After pondering all the statistics and ob-servations set forth above, we are left with

the impression that pneumococcal

menin-gitis at the present time might best be

treated with barge doses of aqueous

peni-cillin (intravenously to start with, if pos-sible, thereafter intramuscularly at 6- or

8-hour intervals) and sulfonamides or perhaps

chloramphenicol. There is no evidence

to-day that intrathecal penicillin is harmful in doses of 20,000 units daily. There is am-ple evidence that the mortality in this

dis-ease should be below 20 per cent,’8’ 602 6465

even where the group includes

predomi-nantly adults: there were 3 deaths among

the 18 patients reported by Waring and

Weinstein63 from their own service,

al-though 12 of the 18 were over 30 years of

age). There is also ample evidence that

further critical clinical studies are greatly needed.

Specific Therapy: Meningitis Due to Gram-negative Enteric Bacilli

This type of meningitis occurs principally, as stated above, in newborn infants. In older

children and adults meningitis due to

en-teric bacilli is apt to be mild, except when

it is due to Pseudomonas aeruginosa.

Seventy-five per cent of the cases due to

the latter follow intrathecal instillation of

contaminated solutions.7#{176} Since gram-nega-tive bacilli cannot readily be differentiated

on smear, and since their susceptibility to

different antibiotics varies widely, it is

es-sential to recover the organism on culture

and determine its drug sensitivity. Clinicians

often wonder how reliable “disc sensitivity

tests” are, and how they correlate with

clinical results: on the whole the

proved most satisfactory in the treatment of

meningitis due to gram-negative bacilli

are sulfadiazine, streptomycin,

chioram-phenicol and intrathecal pobymyxin. An

excellent discussion of the subject,

particu-barby with regard to pobymyxin, is to be

found 111 tile report of Biehl and

Ham-burger.7’ While meningitis in the newborn

due to this group of organisms is, in our

experience, difficult to treat, the physician

does have one great asset on his side,

namely time: these infections are rarely

overwhelming, so that sensitivity tests can

be carried out and treatment planned

ac-cordingly. In the interval, a combination of

streptomycin, Chboromycetin#{174} and

sulfadi-azine should be employed. Particularly

im-portant in this type of infection are: a)

identification of the organism; b) combined

therapy in order to reduce the changes of

drug resistance, and c) prolonged treatment because of the likelihood of relapses.

Treatment of Purulent Meningitis Due to an Unidentified Agent

So far in this section, we have assumed

that the identity of the etiobogic agent had

been established. We reiterate that this is

almost always possible. However, we must

face the fact that in a large part of this

country, pediatricians and general

practi-tioners are inadequately trained in bacteri-ologic procedures and do not have expert

technicians to help them. Only a fraction

of the patients with meningitis are admitted

to the few teaching hospitals where the

laboratory facilities are first rate, or to the

rare small centers where someone has made

a “hobby” of bacteriology. Recognizing this

fact, several studies have been done in an

effort to find what has unfortunately been

cabled a “shotgun” or “blunderbuss” type of

treatment, an outline to rely on regardless

of etiobogic agent. Intramuscular

Terra-mycin#{174}’ has been used for this purpose

with good results, also sulfadiazine and

Ter-ramycin#{174}. There is no doubt that if

terra-mycin, or terramycin and sulfadiazine, are

the only drugs available, they will bring

about recovery in many patients.68’74

How-ever, evidence presented earlier suggests

that terramycin is not the ideal drug for

H. influenzae meningitis, and the evidence

for its efficacy in pneumococcal meningitis

is scanty. Woodward’s group44 approached

the problem by using intravenous

chbor-amphenicol, followed by chioromycetin

palmitate alone ill the treatment of 23

in-fants and children with meningitis due to H.

influenzae, N. meningitidis and D.

pneu-moniae: all but 1 recovered (we believe

the choice of the palmitate form of the

drug was unfortunate since the adequate

spinal fluid drug bevels are reached more

slowly and less surely than with the

crystal-line form). On the Tulane Pediatric Service

at Charity Hospital in New Orleans’6 86

consecutive patients under the age of 10

years with acute purulent meningitis were

treated according to a combined regimen

of sulfadiazine, chboramphenicol and

peni-cillin. Bacteriologic studies showed that in

32 patients H. influenzae was the etiologic

agent, in 26, N. meningitidis and in 14,

D. pneumoniae; in the 14 the etiologic agent was not identified. Seven patients died

(mor-tality 8.1 per cent), which result seemed to

us satisfactory enough to warrant

recom-mending use of this regime in situations

where the etiobogic agent Df purulent

men-ingitis could not be accurately identified.

We realize however, that this regime is by

no means ideal, including as it does,

intra-venous injections which are often

imprac-tical for general practitioners. It is to be

hoped that further large scale, careful

studies along this line will soon be

forth-coming. To date, chboramphenicol bids fair

to be the most satisfactory drug from all

points of view for the treatment of

menin-gitis.

The Problem of lntrathecal Therapy

The pros and cons of intrathecal therapy

have been excellently set forth by

Wein-stein36 and by Hoyne75 respectively. The

batter has long been strongly opposed to

intrathecal therapy for many reasons.

Intra-thecal therapy, at first a necessity in the

menin-270

gitis, was later abandoned. The use of intra-thecal antibiotics in influenzal and

pneumo-coccal meningitis has been given up by most

physicians, even by those who at first

fa-vored it. Only in the treatment of

meningi-tis due to certain gram-negative bacilli,

par-ticubarly PS. aeruginosa, does intrathecal

polymyxin seem at the moment the drug of

choice. It seems to us that Hoyne is right, and that intrathecal therapy is to be avoided

whenever possible, for all of the many

reasons which he sets forth so ably.

The enzymes streptokinase and

strepto-dornase have been used intrathecally in an

effort to prevent formation of adhesions and blockage of spinal fluid circulation. While

they may have an as yet undefined place

in

their use in the great majority of patients

seems unnecessary. Experience has shown

that whenever infection can quickly be

con-trolled with bactericidal antibiotics,

strepto-kinase and streptodornase are superfluous.

When to Stop Treatment

Many patients are cured of acute

bac-terial meningitis, only to develop complica-tions of the treatment itself, such as

hyper-sensitivity reactions, superinfection with

other bacteria or with fungi, gastrointestinal

disturbances, multiple abscesses at the sites

of infection. Some of these complications

are associated with fever and leukocytosis,

and puzzle the inexperienced physician. It

is then useful to know that:

1. Following H. influenzae meningitis,

patients usually recover their appetite and

good spirits within a week. If fever, irrita-bility, anorexia, focal neurobogic signs per-sist or appear, the physician should suspect

otitis media, or subdural effusion or

per-sistence of active meningeal infection.

Sub-dural taps should be performed and the spinal fluid checked. The spinal fluid glu-cose should be normal, the leucocyte count

falling, before discontinuing treatment (this usually happens in 2 to 7 days after

admis-sion to hospital).

2. Bacterial relapses practically never

oc-cur in meningococcal meningitis, so that

symptoms during convalescence are surely

due to something else (suspect particularly

herpes, late sterile joint effusions, drug

sen-sitivity, or pneumonia in patients who were

comatose on admission).

3. Convalescence from pneumococcab

meningitis is often slower than in the above

2 types. Relapses are frequent. Should fever,

irritability, focal neurologic signs appear or

persist, suspect otitis media, pneumonia,

subdural effusion, relapse of meningeal

in-fection, local abscess at the site of injection.

Check the spinal fluid repeatedly during

even the smoothest convalescence;

discon-tinue treatment a week after temperature, spinal fluid culture and sugar are all normal.

COMPLICATIONS ENCOUNTERED

DURING MENINGITIS

With meningococcal infections the most

dramatic complication is peripheral

circula-tory collapse, the Waterhouse-Friderichsen

syndrome. This is not really a complication

of meningitis itself, but of

meningococ-cemia. It is always worth remembering that

peripheral circulatory collapse can

super-vene with infections due to other infectious

agents, particularly the pneumococcus. Two

years ago we saw a small child admitted to

the Charity Hospital with purpuric skin

lesions, cold clammy extremities, a tempera-ture around 107#{176}F.and some stiffness of the neck. The clinical picture was that of

fulmi-nating meningococcemia, but the medical

student was abbe to demonstrate

penumo-cocci in smears from the peripheral blood

as well as from the skin lesions. Another

point worthy of note is that shock in infec-tions is not an “all or none” process: there

are all degrees, depending perhaps in part

on the extent of adrenal cortical damage.76 Shock occurs at the onset of the infection,

within a matter of hours-not days later.

Patients with meningococcal infection

should be particularly carefully watched, therefore, early in their illness: frequent

blood pressure measurements are a good

precaution; helpful to the careful clinician

REVIEW ARTICLE

patient’s hands and feet and see whether

they are warm, or whether cold and clammy.

Recovery from shock in infections has

be-come much more frequent since the

avail-ability of (Irugs such as norepinephrine and

rt799

Other foci of meningococcal infection

such as arthritis0 (seen in 5 to 20 per cent

of all patients), pericarditis, ophthabmitis, are sterilized by the drugs used to treat the

meningitis, but perhaps because of poor

blood supply to some of these areas, the

cob-lections of pus and fluid may be very slow

to clear. For the ocular and cardiac

compli-cations, special therapeutic measures may

be indicated; joint effusions, however,

usually clear satisfactorily without other

treatment than simple immobilization by

means of sandbags.

Follow-up studies on the cranial nerve

complications which follow meningococcal

meningitis showed sixth nerve paralysis in

9 of 300 patients, all with early onset and

early clearing. Some patients also showed

seventh nerve paralysis; here the onset was

apt to be a bit later in the course of the

disease and clearing often took weeks or

months, but was ultimately complete. It is

only fair to say that the sixth and seventh

nerves are much more rarely involved in

children than in adults. The serious cranial

nerve paralysis in children is the eighth,

which is found in about 5 per cent of the

cases, and which is all too often bilateral,

complete and permanent; when it occurs

before the child has learned to speak, this

entails deaf-mutism. Eighth nerve damage

can also occur in other types of meningitis; detailed anatomical studies of the inner ear

from patients with meningitis were made

by Crowe82 and reported in 1930 in a

beauti-fully illustrated paper too little known

to-day. These show clearly that the effect of

meningitis on the hearing is not some

mys-terious effect of a bacterial toxin on the

nerve, but direct damage to the inner ear by

extension of the meningeal inflammation.

Spontaneous hyperglycemia and

glyco-suria are noted in 20 to 30 per cent of

pa-tients in the early stages of meningitis due

to N. meningitidis and D. pneumoniae and

occasionally in meningitis due to other

bacteria.83 They are often associated with

ketosis and diminished tolerance to sugar,

and disappear within 1 to 3 days.

Pneumococcal meningitis has always

brought up the question of the relationship of foci of infection to meningitis. The

dis-ease often arises from ear and sinus

infec-tions, and it seemed logical to operate on

patients and try to drain these foci. Hodes”

in the early 1940’s expressed the view that

mastoids, sinuses, etc., should be operated

on, not because the patient had meningitis,

but only if absolutely necessary, in spite of

the patient’s having meningitis. More and

more clinicians have come round to this

point of view; the general feeling is that it is

better to postpone operative procedures

until the focus is well walled off and until the patient is over the worst of his

general-ized infection. Since many of these foci

clear up under intensive medical therapy,

this means very few operative procedures

indeed in patients with meningitis. Actually

the meningeal infection is probably

sec-ondary in most cases to sepsis, which in turn

is due to septic thrombophiebitis, often of

quite small vessels in the region of the

inner ear. The only patient that we know

of who was operated on in recent years in

Charity Hospital was a 7-year-old Negro

girl treated for 2 days in the outpatient

de-partment with penicillin and sulfadiazine for an acute otitis media. Admitted because of high fever, chills, and delirium, she was

found to have a stiff neck, a draining ear,

definite tenderness over the corresponding mastoid, engorgement of the retinal vessels

and questionable papilledema on the side

of the infected ear. A smear from the thin

ear drainage showed pneumococci. The

spinal fluid was very cloudy but sterile on

culture, much to our surprise, and the sugar

was just barely within normal limits. In

re-constructing the course of the infection, we

decided that it probably had started as an

acute pneumococcal otitis media which had

rapidly spread to the mastoid, thence to the

272 SMITH ACUTE BACTERIAL MENINGITIS

to the meninges, either by direct extension

from the mastoid, or via the blood, or both. The penicillin and sulfadiazine given in the

out-patient clinic had sterilized the blood

and spinal fluid, at least temporarily, but

the process in the ear had progressed. The

treatment consisted in penicillin

intraven-ously in barge doses, subfadiazine

intraven-ously and a blood transfusion, followed by a

simple drainage of the mastoid, which

re-qiiired only half an hour on the operating

table. The child’s convalescence was prompt and complete.

Septic thrombosis of the dural sinuses

with or without meningitis is now

fortun-ately very uncommon. Thrombosis of the

lateral sinus or cavernous sinus usually

fol-lows ear infections and may or may not be

associated with meningitis. Thrombosis of

the longitudinal sinus usually accompanies sepsis or meningitis and is so exceedingly

rare nowadays that one is usually wrong

when one makes the diagnosis! But lateral

sinus and cavenous sinus thrombosis do

occur. A patient with meningitis who has an

eye or ear infection, and who displays

marked signs of increased intracranial

pres-sure, swollen eyelids, engorged retinal

ves-sels or papiibedema should be suspected of

septic sinus thrombosis. Whereas the

out-look for these patients was formerly very

grave, most of them now recover with the

type of management described above.

Hepa-rim does not seem to improve their course.

Subdural effusions as a complication of

meningitis were first reported in 1950 in H.

influenzae meningitis.84 Soon afterwards

they were found to occur in meningitis due

to all of the bacterial pathogens. The

patho-genesis of these effusions is still a matter for

speculation.8’ The most satisfactory explan-ation at the present time is that they occur

as a result of thrombophlebitis involving

the “bridging veins” which traverse the

sub-dural space. Thrombophlebitis has no doubt

always been a common occurrence in

bac-terial meningitis, but few patients survived

to show its after-effects. Subdural effusions are really a complication of severe treated

meningitis. In meningococcal meningitis the

pial exudate is often minimal and recovery

is prompt, and effusions are uncommon. On

the other hand they frequently accompany

influenza! and pneumococcal meningitis.

The effusion usually appears towards the

end of the first week of the patient’s illness:

fever prolonged beyond the usual time,

irri-tability, vomiting, bulging fontanelle, focal

neurobogic signs are the usual clinical

mani-festations. Such effusions are usually sterile,

but may be purulent and yield on culture

the same organism responsible for the

men-ingitis. Sometimes such a subdural

em-pyema remains infected for days after the

spinal fluid is sterile; an area of erythema

over the fontanelle may yield a clue to its

presence. Subdural empyemas seem to cbear

readily, though sometimes slowly, with

sys-temic antibiotic therapy. Subdural effusions are probably best treated by simple aspira-tion of fluid every day or two until clearing. If fluid should persist beyond 3 or 4 weeks-a rweeks-are occurrence-then surgical intervention

should be considered. Since aspiration for

the purpose of removing fluid serves mainly

as a means of decompression, we see no

reason at all to perform subdural taps on

infants convalescent from meningitis unless

an effusion is suspected. That the subdural

effusion itself does some damage by increas-ing intracranial pressure is suggested by the

dramatic improvement in the patient’s

ap-pearance which often follows aspiration.

However, a subdurab effusion is also

objec-tive evidence that the patient has suffered

from an infection severe enough to cause

widespread damage to small blood vessels:

hence the outlook for complete mental and

neurobogic recovery is somewhat less good

in the infant with a subdural effusion.

Hydrocephabus, once such a common

complication of meningitis, is now no longer

seen in any of the common types of

menin-gitis, except as a result of ignorance or care-lessness. Sometimes, in patients with

menin-gitis due to one of the gram-negative bacilli,

the emergence of drug-resistance makes

adequate antibacterial therapy impossible;

under such conditions hydrocephabus

PROGNOSIS

Confronted with a patient suffering from

Illeningitis, the physician’s most reliable prognostic sign is the patient’s state of

con-sciousness. If the patient is oriented and

responsive, the outlook is excellent. The

only exception to this rube is the patient

with fulminating meningococcab sepsis, who

occasionally remains mentally alert even

though in a grave state of shock. The

cloudier the patient’s sensorium, the less

certain is his recovery.

Prognosis has been discussed at some

length with reference to particular types

of meningitis. The chances of survival are

110W very good for any child contracting any

type of purulent meningitis. With

meningo-coccal and H. influenzae meningitis the

mortality is below 10 per cent, or even 5 per

cent; with pneumococcal meningitis it

should be under 15 to 20 per cent. Only in

meningitis of the newborn is the prognosis

more serious.

Recurrences or second attacks of

meningi-tis are nowadays a problem only in

pneu-mococcal meningitis. In this disease,

par-ticularly among adults, repeated attacks may

be seen, often due to different types of D.

pneumoniae. The reason for this

charac-teristic of the disease is not clear; trauma,

congenital skull defects and walled-off

pockets of pus in the arachnoid or dural

membranes have all been blamed.

No discussion of prognosis would be

com-plete without some mention of the patients

who survive the acute phase of the disease

but later display evidence of neurobogic

damage. Some patients convalescent from

severe meningitis, especially pneumococcal

or influenzal, are subjected to

pneumoen-cephalography and are found to have a

di-lated ventricular system.62’ 86 In others,

inequality of the deep tendon reflexes, or

unwillingness to use a hand, or inability to

bear weight on one beg suggest focal brain

damage. To evaluate the long-term

implica-tions of these findings is almost impossible.

One is always astounded to see, in

follow-ing such children, how many show complete

clearing of symptoms within a matter of

days or weeks. The incidence of epilepsy or

of slight degrees of mental retardation are

particularly hard to assess, since there was

usually no evaluation of the child’s mental

and neurobogic status prior to illness. Fur-ther detailed considerations of this facet of the management of patients with meningitis

are to be found ebsewhere.89#{176}

SUMMARY AND CONCLUSION

Man, alone of all animal species, seems

susceptible to meningitis, probably because

of the very large amount of blood which

perfuses his brain, thereby increasing the

opportunities for blood-borne infection.

In-fants and young children, before they have

acquired immunity to the common bacterial pathogens, are particularly prone to menin-geal infection. Since they outwardly display

less characteristic signs and symptoms of

meningeab irritation than do adults,

diagno-sis is often delayed and the chances for

recovery correspondingly impaired.

Cyano-sis, fever, vomiting in the newborn; fever, drowsiness, jitteriness, tenseness of the fon-tanelle in older infants; headache, vomiting,

and stiffness of the neck in children, and so-called febribe convulsions in patients of any

age, should point to the possibility of

menin-gitis. Examination of the spinal fluid

ob-tained by lumbar puncture is the only

com-pletely satisfactory way to establish the

diagnosis, unless petechiae are present from

which an organism can be recovered on

smear. All things considered, the best

chemotherapeutic agent for patients with

H. influenzae meningitis is crystalline

chlo-ramphenicol; for those with meningococcal meningitis sulfadiazine, and for those with

pneumococcal meningitis penicillin and

sub-fadiazine. Only if the etiobogic agent cannot

be identified should resort be had to drug

combinations such as penicillin, sulfadia-zine, and chboramphenicol; or to Terramy-cm#{174}which is optimal in no type of

meningi-tis, but fairly good in all. Whatever the

chemotherapeutic agent employed, the

phy-sician should always remember that the

management of patients with meningitis