Principles of \eurtaurgary.

edited by Robert G. Grossman-

Published by Harm

CHAPTER 10

Focal Infections of the Central Nervous System,
Skull, and Spine

Perry Black and Michael E. Carey

Brain Abscess, 179

Pyogenic Brain Abscess, 179
Intracranial Tuberculoma, 193
Herpes Simplex Encephalitis (HSE), 195
Parasitic Brain Abscess, 196

Fungal Brain Abscess, 200
Acquired Immunodeficiency Syndrome

(AIDS), 202

Osteomyelitis of the Skull, 204

Spinal Abscess, 204

Pyogenic Infections, 204
Spinal Tuberculosis, 210
Parasitic Spinal Infection, 211
Fungal Spinal Infection, 212

Conclusion, 212
References, 213

Nervous system infections may be caused by bacteria,
viruses, fungi, or parasites that can cause diffuse or local-

ized disease. This chapter deals primarily with focal in-
fections of the nervous system that produce a mass of
varying size and that may be amenable to surgical inter-
vention. Because primary attention is directed to those
lesions with neurosurgical implications, diffuse infec-
tions—such as meningitis or encephalitis (other than
herpes simplex encephalitis)—are not considered here.

Despite the availability of antibiotic therapy, focal bac-

terial infections of the central nervous system (CNS)
continue to pose a serious problem with disturbingly
high mortality and morbidity. As outlined in this
chapter, successful management of such infection&,en-
tails the combination of both surgical-decompression of
the expanding lesion and carefully selected antibiotic
therapy. This is best achieved by a collaborative effort on
the part of the neurosurgeon and consultants in in-
fectious disease and clinical microbiology, all contribut-
ing the expertise of their respective disciplines.

P. Black: Department of Neurosurgery, Hahnemann Univer-

sity, Philadelphia, Pennsylvania 19102-1192.

M. E. Carey: Department of Neurosurgery, Louisiana State

University, New Orleans, Louisiana 70112-2822.

BRAIN ABSCESS

Pyogenic Brain Abscess

Hematogenous ("metastatic") brain abscesses occur

when bacteria from elsewhere in the body enter the
blood stream and lodge within the brain. Alternatively,
brain abscesses may arise from direct brain trauma, from
an adjacent inflammation such as osteomyelitis of the
skull, or from sinus/mastoid infection. Occasionally,
brain abscesses are a sequela of meningitis or occur post-
operatively as a complication of craniotomy.

Epidemiology

Cerebral abscess may affect individuals of all ages,

with peaks in the preadolescent, young adult, and mid-
dle years (1,2). Males are more frequently involved than
females (3-5). Experience in industrialized countries in-
dicates that an active hospital neurosurgical service may
expect to see from 4 to 10 patients each year with pyo-

genic brain abscess (6-10). The average neurosurgical
practitioner in the United States may see but a single
case each year (11). The situation in developing coun-
tries, however, is quite different. In India, pyogenic brain
abscesses account for approximately 8 to 18 percent of

179

180 / CHAPTER 10

all intracranial space-occupying masses (12-14), and in

the People's Republic of China, a busy neurosurgical ser-
vice may see up to 20 brain abscesses a year (5).

The spectrum of brain infection varies considerably

worldwide. Parasitic and tuberculous brain infections
are more serious problems than pyogenic abscesses in
many countries. Rodriguez in Mexico City reported that

cysticercosis was responsible for 85 percent of all brain

infections, that tuberculomas accounted for 11 percent,
and that pyogenic abscesses caused 3 percent (15). The
etiology underlying pyogenic brain abscesses also varies,
depending on environmental factors such as trauma (16)
and the widespread existence of sinus/mastoid disease

(8). The availability of neurosurgical care and the pres-
ence of special units handling many patients with con-

genital cardiac abnormalities (17), cystic fibrosis (18), or
immunologic suppression (19) may also alter the under-
lying etiology.

Etiology

Besides cyanotic heart disease with right-to-left car-

diac shunts, pulmonary A-V fistulas may lead to brain

abscesses because blood circulates from pulmonary arter-

ies to pulmonary veins, bypassing the effective bacterial
filtering ability of the pulmonary capillaries (20,21). In
infants and children, cyanotic congenital heart disease is
the most common cause of brain abscess (24 percent of
cases); other major sources of brain abscesses in children

are head trauma, infections of the ear, nose, and throat,

and cases of undetermined origin (22).

Hereditary hemorrhagic telangiectasia (HHT) is a vas-

cular dysplasia in which capillaries and small venules are
deficient in muscle and elastic tissue. Arterial ectasias
and arteriovenous fistulas are also common. More than

200 cases of CNS symptoms associated with HHT have

been reported. Although many of the CNS complica-

tions of this disease are consequent to cerebral arterio ve-

nous malformations (AVMs), CNS infections ajre likely
to occur in association with pulmonary AVMs. Patients
with HHT have about 1000 times greater risk of a brain
abscess than the general population (23). Brain < bscesses
have been responsible for about 13 percent of all CNS
complications of HHT (24).

Several reports associate brain abscesses with cystic

fibrosis owing, most likely, to recurring pulmonary in-

fections seen in this disorder (18,25,26).

Septic infarction may complicate the clinical course of

malignancies, particularly leukemia, carcinoma, and
lymphoma (27). Often patients with systemic malignan-

cies are immunosuppressed either because of the disease

or in response to treatment. Thus, about 0.5 percent of

those dying of systemic cancer will have significant clini-
cal symptoms referable to septic brain infarcts. Aspergil-

lus and Candida species are the most common causative
organisms.

Acquired immunodeficiency syndrome (AIDS) is as-

sociated with widespread infections, both systemically
and within the CNS. Surprisingly, CNS infections in
AIDS are usually caused by protozoa (e.g., toxoplasmo-
sis) or fungi rather than the common pyogenic organ-
isms.

Types of Abscesses

Traumatic Brain Abscess

These abscesses may rise from open fractures of the

skull, particularly if the dura is torn. Jennett and Miller
found an infection rate of 10.6 percent among 359 such

fractures, usually occurring from inadequate initial

wound care (28). In other series the incidence of ab-

scesses consequent to trauma has varied from

1

3 to 28

percent (3-7,10,29). This may depend to some extent on

socioeconomic circumstances of various countries and
neurosurgical referral patterns. Brain abscesses conse-

quent to penetrating missiles incurred in war are a spe-
cial category. Carey, Young, Rish, and Mathis (30) re-
ported a 2 percent incidence of such abscesses. Rish and

colleagues (31) analyzed Vietnam data and found a 3

percent incidence (37 brain abscesses among 1221 pa-
tients with missile wounds to the brain). Many, but not
all, of those developing a late brain abscess had asso-

ciated retained bone fragments. More important than
retained bone alone, however, were concomitant orbital
facial wounds, wound complications, and multiple oper-
ative procedures on the brain.

Abscess from Adjacent Infection

Chronic infections of the ear, nose, and throat are po-

tential sources of infection that may spread to adjacent
brain. In one series, infections of the middle ear and

mastoid were the most common source (87 percent), fol-
lowed by the paranasal sinuses (12 percent) and tonsils (1
percent) (32). In another series, 45 percent of patients

with chronic mastoiditis (cholesteatoma) developed in-
tradural sepsis; the bulk of these complications consisted
of temporal lobe or cerebellar abscesses, and a smaller
number were supratentorial or posterior fossa subdural

empyemas. Acute mastoiditis was only occasionally (7
percent) associated with intradural infection (33). Al-
though antibiotics have drastically diminished the inci-
dence of intracranial extension of middle ear/mastoid

infection, continued diagnostic vigilance concerning

such complications is recommended (34). Bacteria from
an adjacent infected paranasal sinus or mastoid may

reach the brain by direct extension from the involved
sinus through the underlying dura. Bacteria may also
reach the brain by local metastatic spread through ve-
nous channels that drain the sinus and enter the intracra-

nial compartment as emissary veins. Paranasal sinus in-

fections usually result in frontal lobe abscesses (Fig. 1).

Mastoid infections may cause temporal lobe or cerebel-

lar abscesses (35). Temporal lobe abscesses are more

common because the roof of the middle ear is thinner

than the posterior wall.

Scalp infection, infected subgaleal effusions, or cepha-

lohematomas may also lead to brain abscesses with or

without associated osteomyelitis. Bacteria from infected

bone of the skull (osteomyelitis) may spread directly into

the epidural space and reach the subdural compartment

and brain by direct extension through the dura. Bacteria

from a scalp infection or osteomyelitic bone also may

reach the subdural space and brain via emissary veins.

Cerebral abscess developing as a late complication of

cervical traction occurs rarely; this is thought to occur by

penetration of the inner table by the pins of the tongs or

halo unit (36).

Hematogenous (Metastatic) Brain Abscess

These occur when bacteria from elsewhere in the body

colonize the brain. Blood-borne bacteria tend to flow

into the middle cerebral artery, so hematogenous ab-

scesses are usually located in the posterior frontal and

parietal lobes. Chronic pulmonary infections such as
bronchiectasis are an especially common primary source

CNS INFECTION

•vs

FIG. 1. CT scan (with IV contrast), showing ring-enhance-

ment, of a 47-year-old man with right frontal brain abscess.

The patient presented with seizures. A craniotomy was per-

formed with drainage of the abscess. The patient initially did

well, but the abscess reaccumulated two weeks later and

was drained again. Frontal sinus infection was suspected as

the etiological source, and the brain abscess cleared after the

frontal sinus was exenterated.

of bacteria, but skin, pelvis, mouth, and long bones air

other underlying infective foci. Bacterial endoeafiSiis

may also lead to brain abscesses, particularly when heart

valves are infected with Staphylococcus aureus or Group

D streptococci (37). In approximately one-fifth of

the cases, no apparent source of infection can be

found (2,38).

Metastatic brain abscesses initially occur at the gray-

white junction, where blood flow in the brain capillary

bed is slowest, but what actually allows a bacterium to

adhere to and penetrate a brain capillary is unknown.

About 2 percent of all brain abscesses occur in patients

with cyanotic congenital heart disease (39). Individuals

with cardiac venous-to-arterial (V-A) or "right-to-left"

shunts are 10 times more likely than normal persons to

develop brain abscesses (17) because bacteria intermit-

tently present in venous blood may bypass the lungs,

enter the arterial system, and pass to the brain. Most

cardiac V-A shunts arise as a consequence of Fallot's

tetralogy, or dextroposition of the great vessels. Further-
more, patients with cyanosis secondary to V-A shunting

are at greater risk of developing brain abscesses because

the associated elevated hematocrit increases blood viscos-

ity and reduces blood flow. This leads to microinfarction

of the brain, which may then become colonized by bacte-

ria. Reduced tissue Po

2

concentration in these patients

also may enhance bacterial growth within the brain (17).
Patients with cyanotic, congenital heart disease also de-

velop strokes from thromboembolic disease. Some au-

thors believe that neurological signs and symptoms in

this population are more commonly caused by brain ab-

scesses than by vascular occlusion or hemorrhage (40).

They therefore advocate steps to immediately diagnose

brain abscess and to begin antibiotic therapy promptly

when patients with congenital heart disease develop a

"stroke."

Postmeningitic Brain Abscess

Considering the frequency of meningitis and the infre-

quency with which this type of abscess has been re-

ported, this complication of meningitis must be quite

rare in the antibiotic era. However, brain abscesses may

complicate pyogenic meningitis, presumably by direct

bacterial colonization of the brain. Neonatal meningitis

caused by Citrobacter is of particular concern, however.

because about 40 percent of these patients develop brain

abscesses (41,42). Antecedent brain softening, as from
venous infarction, provides an excellent culture medium

for bacteria.

Pathology

Initially, a pyogenic brain abscess begins as a focal area

of bacteria-laden cerebritis. Host defense mechanisms

182 / CHAPTER 10

begin to wall off the infection by capillary proliferation
from the surrounding brain. Fibroblasts from the prolif-

erating capillaries lay down collagen fibers to contain the

purulent focus. Britt and colleagues (43,44) demon-
strated five histological layers in brain abscess: zone 1, a
necrotic center; zone 2, an inflammatory infiltrate

mixed with macrophages and fibroblasts surrounding

the necrotic center; zone 3, collagenous capsule forma-
tion; zone 4, cerebritis with neovascularity and perivas-
cular infiltration of inflammatory cells in the adventitial
sheaths of blood vessels surrounding the abscess; zone 5,

reactive astrocytes, gliosis, and cerebral edema. Brain

capillaries, from which fibroblasts arise, are more numer-
ous in the cortex and less plentiful in the white matter.
Abscess encapsulation, therefore, is more likely to be
complete superficially and deficient in the deeper white
matter. Experimental data suggest that hematogenous

abscesses are less well encapsulated than abscesses cre-
ated by direct bacterial implantation, possibly because

cerebral ischemia associated with metastatic abscess re-
tards capsule wall formation (45).

Britt and colleagues (43,44) studied experimental aer-

obic brain abscess formation and determined four devel-
opmental stages: early cerebritis (1-3 days); late cerebri-
tis (4-9 days); early capsule formation (10-13 days); and
late capsule formation. Whalen and Hilal's (46) clinical
data also indicated that brain abscess encapsulation re-

quires about two weeks. Britt and associates also studied

experimental abscess formation with Bacteroides, an an-
aerobic organism that proved_inuchjnore virulent than
aerobic bacteria. Animals infected with Bacteroides did
not survive into the late capsule formation stage. Viru-
lent bacterial infections of the brain parenchyma were

associated with extensive brain necrosis and edema. Gen-

erally, a brain abscess acts as an acute or subacute ex-
panding intracranial mass (47), often associated with
enormous reactive brain swelling. The combination of

the abscess mass and swelling may compress vital struc-
tures and may cause death by transtentorial herniation.
Because of deficient encapsulation in the deep portion of

the abscess, it may extend centripetally and rupture into
the ventricle (48), causing fatal ventriculitis/meningitis.

Clinical Manifestations

Brain abscess presents clinically in various ways (39):

(1) The infectious syndrome—signs of infection, such as

pain, redness, and swelling about an infected frontal
sinus, may be local. Sometimes only general aspects

of infection may be evident, such as fever, elevated

white blood cell (WBC) count, neutrophilia, and in-

creased blood sedimentation rate.

(2) The intracranial hypertension syndrome—papille-

dema, nausea, vomiting, and headaches.

(3) The syndrome of focal neurologic signs—for exam-

ple, hemiparesis or dysphagia.

(4) The meningeal syndrome—stiff neck.

(5) Psychic disturbances—especially an alteration in the

level of consciousness.

In general, headache is the most common presenting

complaint. Fever is present in only half of the patients.
Less than half have a focal neurological deficit, and nu-
chal rigidity is uncommon (1,2). The peripheral WBC
count is normal in 40 percent of the patients. A useful
diagnostic feature is the fact that the erythrocyte sedi-

mentation rate (ESR) is usually elevated, except in pa-

tients with cyanotic heart disease, in all of whom the
ESR is normally low owing to their polycythemia (2,47).
Signs and symptoms associated with a brain abscess vary
according to the location of the abscess, its size, and the
presence or absence of concomitant meningitis. Thus,
the affected individual may have headache, papilledema.
and an altered state of consciousness; motor, speech, or
visual disturbances; focal or generalized seizures; ataxia;
or signs of meningitis.

Brain abscesses are rare in the neonatal period (49,50).

Diagnosis of brain abscess in the neonate"is often diffi-

cult because few specific signs or symptoms Indicating

intracranial infection are present: fever is often absent
but vomiting or an enlarging head may be present (50).
Convulsions are the most constant clinical sign in these

young patients (51,52). In the series of Sutton and
Ouvrier (50), the clinical diagnosis of brain abscess was

suspected in only 2 of 12 infants. Sutton and Ouvrier

therefore recommended that an ultrasound, CT scan, or
both be done in all infants presenting with bacterial men-
ingitis.

Diagnostic Studies

When computerized tomography (CT) is available,

this is the primary screening modality for diagnosis of
brain abscess. Equally effective, though less widely avail-
able, is magnetic resonance imaging (MRI). Radionu-
clide (RN) brain scanning is also useful in diagnosis
when CT scanning is not available or is inconclusive.
Plain skull films of the head are generally of limited
value but may be useful in certain circumstances. Elec-
troencephalography (EEG) may provide evidence of a

localized space-occupying mass. Its use has largely been

replaced by CT or MRI scanning, when these are avail-
able. Lumbar puncture is often contraindicated because
of the high risk of cerebral herniation, but it may be
considered with neurosurgical consultation if meningitis
must be excluded. Angiography is now used rarely for

diagnosis of brain abscesses, except when modalities

such as CT or MRI are unavailable. Ultrasound may be
useful in identifying cerebral shift, especially in young

CNS INFECTIONS / 183

children when the more definitive diagnostic modalities
are unavailable.

Computerized Tomography

CT scanning has revolutionized the diagnosis of brain

abscess (Fig. 1). The frequency with which CT identifies
brain abscesses reflects the prevalence of the disease in
the population. Michel (France) reported 19 brain ab-
scesses per 8,500 scans (0.2 percent) (53), and Danziger
(South Africa) observed 90 abscesses in 11,300 CT scans
(0.8 percent) (6). In addition to promoting early diagno-
sis, CT scanning allows the clinician to monitor the evo-
lution of the abscess before and after treatment. It has
allowed the successful treatment of abscesses in difficult

locations, such as in the thalamus or brain stem, and in
multiple brain abscesses (42,54,55).

One early study indicated that CT scanning had about

a 90 percent accuracy in diagnosing brain abscesses (56),

but it was noted that false negative CT scans were caused

by imaging artifacts, failure to give contrast media, and
scanning very early in the course of the disease, before
encapsulation had occurred. Use of contrast medium for

enhancement is mandatory in order to maximize the

diagnostic accuracy of the scan. CT scan of brain abscess

generally shows a ring-like pattern of smooth, uniform
thickness that encloses a hypodense region. The dense
ring, in turn, is surrounded by a hypodense area, presum-
ably cerebral edema. Ring enhancement has been attrib-

uted to breakdown of the blood-brain barrier (BBB), vas-
cular granulation tissueroriuxury perfttsion (57). Some

abscesses appear biloculate or septate on scans.

Ring enhancement on CT scanning may appear

within two days of the onset of neurological symptoms.

Experimentally (58,59), a ring pattern consistent with

abscess also has been observed in localized cerebritis

(60). Abscess "encapsulation" demonstrated by CT
scanning may not correspond to histologic encapsula-
tion; CT ring enhancement was seen with either cerebri-

tis or brain abscess (61). This observation is of more than

theoretical interest for two reasons: first, if a diagnosis of

brain abscess was made by CT scan but nothing could be
aspirated by needle tapping because the ring-enhancing
image was really cerebritis, additional brain damage
could result from repeated cannulations in search of the

abscess. Secondly, cerebritis is more amenable to antibi-
otic treatment than is a brain abscess. Possibly some of

the reported cures of brain abscess from antibiotic ther-
apy alone were in reality cures of cerebritis.

Even under experimental conditions, investigators ini-

tially had difficulty distinguishing cerebritis from abscess
by CT (59). Clinical and experimental studies have distin-
guished between cerebritis and frank brain abscess by

means of serial CT scans (58,62). In order to stage the
brain abscess by this method, patients were given about 2

ml/kg of contrast medium intravenously. CT scans were
then obtained at 5, 10, 20, 30, 45, and 60 minutes after
injection. With cerebritis, the ring of enhancement in-
creased for the first 10 to 20 minutes, then plateaued for
an hour. The enhancing ring was thick and diffuse when
first seen about the periphery of the lesion. With time,
the ring tended to migrate toward the center of the le-
sion, which sometimes did not fill in with contrast. Brain
abscesses, on the other hand, showed rapid ring contrast

enhancement by 5 to 10 minutes and rapidly faded by 30
minutes. Steroid administration may decrease CT en-
hancement of brain abscesses in their early stages (63),
but attenuation of CT ring enhancement of a brain ab-
scess with steroid must not be misinterpreted as resolu-
tion of infection (64).

Cystic glioma, tumor metastases, and infarct are com-

mon lesions that may mimic abscess on CT scans. Glio-
mas and metastases tend to have more irregular capsules
when enhanced, but nevertheless, their CT image may

be confused with that of an abscess. In one recent analy-

sis, "malignant tumor" was the initial scan diagnosis in 8
of 26 instances of proven brain abscess (65). Rapid
changes on sequential CT scans favor infection. Provid-
ing clinical history to the radiologist may improve the

accuracy of CT diagnosis.

CT scanning has proved to be an effective means for

following patient progress after treatment. Some investi-

gators believed that abscess capsule enhancement seen
on CT diminished after drainage and that reduced en-
hancement indicated successful treatment. Conversely,
persistent capsule enhancement on follow-up CT studies
was thought to indicate that the abscess had refilled or
extended (56). Subsequent studies, however, have indi-
cated that even after complete, successful surgical exci-

sion of the abscess, a ring-like zone on contrast enhance-

ment surrounding a low-density zone may be present for
some time (57). Eventually, however, this post-excision
ring gradually fades and the excision site is marked only
by a region of low cerebral density. Although this persis-
tent ring tends to be more irregular than most abscess
capsules, differentiation from recurrent abscesses may

require considerable clinical acumen plus further se-

quential CT scans.

Magnetic Resonance Imaging (MRI)

MRI is effective in demonstrating brain abscesses as

well as other infections of the brain (66). This imaging
modality is more sensitive than CT in detecting the se-

quential changes in the development of a brain abscess

(67). Brant-Zawadzki and associates (68) compared
MRI and CT imaging of experimental brain abscesses.
In the cerebritis stage, CT scans showed ring enhance-
ment corresponding to the inflammatory zone and a
surrounding large area of low attenuation. Spin-echo

184 / CHAPTER 10

MRI showed high intensity in both the dense inflamma-

tory zone and surrounding edematous brain. This high
intensity area on MRI was more extensive than brain
changes demonstrated by CT. The central core of the
abscess was represented on the MRI by a lower intensity
area. CT scanning of encapsulated abscesses showed dis-
crete ring enhancement of the capsule, and the spin-echo
MRI showed a more circumscribed, peripheral, high-in-
tensity area. The authors suggested that MRI is more

sensitive than CT in the early detection of cerebritis as

well as adjacent cerebral edema (68). CT and MRI
proved to be equal in detecting the development of cen-
tral necrosis within an abscess. MRI could differentiate

tissue liquefaction from simple edema because edema is
seen as an area of high intensity on spin-echo images,

while liquefaction is shown as a low intensity region.
Capsule staging was better assessed by CT scanning.

Repeated imaging is necessary to follow the course of

an abscess; in this regard, an advantage of MRI is the
absence of radiation exposure. Gadolinium-DPTA, a
paramagnetic contrast agent, enhances MRI imaging as

a function of penetration of the BBB (69).

Radionuclide (RN) Scans

Radionuclides penetrate the BBB in the presence of

inflammation. This alteration allows large molecules

tagged with a radioactive moiety to penetrate the BBB

and accumulate in the region of a lesion. Isotopic brain

scans accurately identify 90 percent of all supratentorial
abscesses. PosteriortossaTesions may be missed, how-
ever, because of the overlying suboccipital muscles that

also take up the isotope. Radioisotope is concentrated in

the abscess capsule and surrounding brain (70). The oc-
casional occurrence of the "ring" or "doughnut" sign
may suggest a brain abscess as the isotope is taken up by
edematous brain and capsule but not by the pus within
the abscess. Although RN scans may not distinguish be-
tween abscess, cerebritis, or neoplasm, they may delin-
eate early cerebritis and diffuse intracranial infection
better than CT scans do (71), and therefore RN and CT
scans may be considered complementary tests (72). In
one series, RN delineated eight of eight brain abscesses

and CT delineated seven of the eight. Confidence in RN

is important because this diagnostic tool may be avail-
able in areas where the more expensive CT is not. The
use of technetium"

m

-DPTA with delayed scans en-

hances the diagnostic sensitivity of RN scans even fur-

ther (73).

cranial space-occupying mass. Rarely, gas-forming bacte-
ria within an abscess may cause diagnostic lucencies on
skull films.

Electroencephalography (EEC)

This modality may be a useful screen for brain abscess

because of the characteristic focal, low-frequency delta
wave associated with this lesion. Although diagnosis by
EEG cannot be expected to be as precise as CT or MRI
scanning, EEG is useful in situations when CT or MRI
scanning are not available. In one recent series, EEG
predicted 11 of 13 abscesses, radioisotopic brain scans
localized five of six abscesses, and carotid arteriograms
localized six of seven lesions (74). Michel compared the
efficacy of EEG and CT scans (53). Among 19 cases,

EEG patterns typical of brain abscesses were seen in 6
(32 percent), and CT images diagnostic of abscess oc-

curred in 13 (68 percent).

Lumbar Puncture

This test should not be performed when a brain ab-

scess is suspected because it may lead to transtentorial or
tonsillar herniation; furthermore, it rarely provides bacte-
riological data because brain abscesses only occasionally
shed organisms into the subarachnoid space. Risks of
this procedure in the evaluation of a brain abscess out-
weigh its benefits (2,4,5,47,75).

Cerebral Angiography

Cerebritis results in a characteristic capillary and early

venous blush. This angiographic blush is possibly caused

by increased cerebral perfusion associated with inflam-

mation in addition to the accumulation of contrast in
dilated capillaries about the involved area. The angio-
graphic diagnosis of brain abscess is made by evidence of
a mass lesion and cerebritis. Evidence of leptomeningeal

inflammation is indicated by the pooling of contrast
within sulci and by halo formation about arterial struc-
tures. There is also angiographic staining of neovascular
tissue within the abscess (the "ring" sign) (76,77). When
CT or MRI scanning is not sufficiently diagnostic, arteri-
ography may differentiate tumors from abscesses if neo-
vascularity typical of tumor vessels is seen within the

mass lesion.

Skull X-Rays

These are helpful and may show such contiguous

sources of infection as osteomyelitis of the skull or sinus/
mastoid disease. A shift of the pineal indicates an intra-

Ultrasound

Yang found echoencephalography 87 percent accu-

rate for lateralizing supratentorial abscesses (5). Occa-
sionally, ultrasound is capable of visualizing an abscess

CNS INFECTIONS / 185

wall. This technique may prove particularly useful for

abscess diagnosis in infants with open fontanelles.

Organisms Causing Pyogenic Brain Abscess

Streptococci and staphylococci are the most frequent

cause of purulent brain abscesses (1,78-83). In the antibi-
otic era, more mixed infections caused by gram-positive
cocci and gram-negative rods have appeared. Streptococ-
cus faecalis, Proteus, and Bacteroides fragllis are the
organisms most commonly implicated in polymicrobial
otogenic abscesses (84). Clostridium is the organism
most commonly found in postcraniotomy infec-
tion (84).

Anaerobic bacteria have been increasingly recognized

as sources of infection of the CNS, owing to improved

methods of isolation and identification. The importance
of anaerobic organisms has been recognized since Heine-
man and Braude's study demonstrated their frequency

in brain abscesses (85). In another study, anaerobic bacte-
ria were isolated from 70 percent of the brain abscesses
(86). Bacteroides species, anaerobic streptococci, and fu-
sobacterium, either singly or in combination, are the

most common anaerobes that cause brain abscesses

(43,80,86-89). Bacteroides fragilis is an obligate anaer-

obe that tends to produce brain abscesses, especially

those following chronic middle ear and mastoid infec-

tions. The outer cell wall membrane of B. fragilis reacts

with serum complement, which compjelelyaborishes

polymorphonuclear movementrTTTis may give the bacte-

ria enough time to replicate and overwhelm host de-

fenses. These organisms also produce endotoxins, hepa-

rinase, collagenase, and hyaluronidase, which may
account for their virulence. Patients with chronic dis-
eases and patients who are immunosuppressed are more

likely to have brain abscesses caused by unusual bacte-

ria, such as Listeria monocytogenes, or by fungi. The

protozoa Toxoplasma gondii is a common cause of CNS

infection in patients with AIDS (90,91).

Antimicrobials

Antimicrobials exert their antibacterial effects in a va-

riety of ways. Some, such as the penicillins (92), cephalo-
sporins (93), and vancomycin (94) inhibit bacterial cell
wall synthesis. Others, such as the aminoglycosides (in-
cluding streptomycin) (95), tetracyclines (96), chloram-
phenicol (96), erythromycin (97), and rifampin (98) in-
hibit RNA synthesis. Chloramphenicol is bacteriostatic
because it inhibits microbial protein synthesis by inhibit-

ing peptidyltranferase. This action blocks polypeptide
formation at the ribosomal site in the endoplasmic reticu-
lum but does not produce irreversible cell damage. Met-

ronidazole is bactericidal and damages bacterial DNA or

other molecules (99). The sulfonamides inhibit intrabac-

terial folate synthesis (100). The polymyxins interact
with cell-wall phospholipids and act as cationic deter-

gents or surfactants, and they increase the permeability
of the bacterial cell wall (101); however, those agents are
obsolete today and are no longer used.

Penetration of substances across the BBB is propor-

tional to their lipid solubility (102,103). Antibiotics with
greater lipid solubility pass through the BBB more
readily than do non-lipid-soluble ones. Nonionized mol-
ecules pass through the BBB more readily than ionized
molecules do. Penicillin G is nonlipophilic and is highly

ionized at physiological pH. Hence, penicillin and other
beta-lactam antibiotics do not cross the normal BBB
well. With inflammation, the BBB breaks down, allow-

ing penicillin to enter brain extracellular space.

Antibiotics highly bound to plasma proteins have low

effective plasma concentrations, and consequently, pas-
sage of protein-bound antibiotics across the BBB is poor.
High molecular weight and complex antibiotic molecu-
lar structure also impede BBB crossover. This latter fac-
tor may help explain the poor passage of the aminoglyco-
sides from blood to brain. Even with meningitis,
penetration of the aminoglycosides can be achieved only

by intrathecal administration (95). In neonates, how-

ever, aminoglycosides do penetrate the CSF in adequate
concentration. These factors indicate why antibiotics ac-
cumulate poorly in the CNS. Theoretically, active trans-
port mechanisms within the BBB might enhance the

passage of some antibiotic molecules from plasma to
brain extracellular space.

Clinical data have shown that CSF tetracycline levels

are 10 to 20 percent of plasma levels (96). Under normal
conditions, CSF erythromycin is 0 to 2 percent of the
plasma level. With meningitis, however, the CSF con-

centration of this drug may increase to 5 to 10 percent

that of plasma. Normally, vancomycin does not cross
from plasma to CSF, but in the presence of meningitis,

bactericidal levels of the drug may be found in spinal

fluid. Despite this fact, up to 3.0 to 5.0 mg of vancomy-
cin may be given intrathecally to combat infection if no
response to parenteral administration occurs (94).
Whereas "first generation" and most "second genera-
tion" cephalosporins do not cross the BBB well, cefurox-

ime, a "second generation" cephalosporin, and all "third

generation" cephalosporins cross the BBB readily (93).

Chloramphenicol is 60 percent protein-bound in

plasma. CSF/plasma ratios of the drug vary from 35 to

65 percent regardless of the administration route and the

degree of meningeal inflammation. Because the level of
protein in CSF is so much lower than that in plasma,

Chloramphenicol may be relatively more active in CSF

than in blood (104). Most of the organisms involved in

brain abscesses are susceptible to Chloramphenicol. Phe-
nytoin may increase the effective serum chlorampheni-

col concentration (even into toxic ranges), but pheno-
barbitol may decrease it (105). The penicillins are

186 / CHAPTER 10

bactericidal for most of the common pathogenic bacte-

ria, but some pneumococcal and group B streptococci

may be resistant. Metronidazole is soluble in water and

is essentially nonionized at physiological pH. This mole-

cule, therefore, rapidly crosses the BBB and cell mem-
branes to achieve anaerobicidal concentrations in the
CSF. It is excreted in the urine. A transient opening in
the BBB may be induced to allow substances that ordi-
narily do not pass the barrier into the brain extracellular
space (106). Neuwelt increased gentamycin delivery to
the brain 30- to 45-fold in rats by giving the drug directly

into the carotid artery following BBB opening by manni-
tol (107). This approach may have human application.

Human data suggest that penetration of antibiotics

into brain abscesses is unpredictable (80). Fusidic acid
has "good" abscess accumulation. Chloramphenicol, be-

ing a small molecule, penetrates the normal BBB well,

but unfortunately its uptake into abscesses has been er-
ratic. Penicillin and ampicillin penetrate abscesses rea-
sonably well, and third-generation cephalosporins pene-
trate to produce adequate concentrations.

Black, Graybill, and Carache documented six cases

where antibiotics penetrated abscesses in reasonable

concentrations, yet the patients continued to deteriorate

until surgical treatment was undertaken (108). They
concluded that antibiotics failed once they had reached
the contents of the abscessjggcause of poor antibiotic

activity within the lesion. They hypothesized that the

purulent milieu within the abscess inhibited antibiotic
effectiveness.

Experimental evidence suggests that steroid adminis-

tration in the treatment of experimental brain abscesses

retards the passage of some antibiotics through the BBB
and into the region of infection. These data suggest that
antibiotic dosages should be increased to optimize drug

tissue concentrations if steroids are used to treat the
edema associated with brain abscesses.

Knowledge of the original infective source—even be-

fore the organism has been identified—is useful when
selecting initial antibiotic therapy because specific organ-

isms are commonly associated with certain inciting foci.

According to DeLouvois (109), abscesses of sinusitic ori-

gin are often caused by carboxyphilic streptococci, fre-

quently Streptococcus milleri, which are highly sensitive
to penicillin. Penicillin (16 to 24 megaunits/24 hrs),

therefore, should be included in the treatment of brain

abscesses of sinusitic origin. However, mixed aerobic
and anaerobic organisms (such as Bacteroides) resistant
to penicillin have been cultured from sinus infections

(110). Therefore, it may be advisable to treat abscesses of

sinusitic origin with metronidazole in addition to peni-

cillin. Abscesses from mastoid infection are caused by a
wide range of aerobic and anaerobic bacteria. Penicillin,
chloramphenicol, and metronidazole (88,111,112), or
ampicillin, gentamycin, and metronidazole should be

started intravenously when treating otogenic brain ab-

scesses because of the high probability of mixed gram-

positive, gram-negative aerobic and anaerobic bacteria,
including Bacteroides. For gram-negative organisms, ce-
fotaxime and ceftriaxone are highly effective. In some
cases, clavulanic acid, combined with ticarcillin, has also

been recommended (113). Posttraumatic abscesses are
frequently caused by Staphylococcus aureus (109). Naf-
cillin would be a good initial antibiotic choice for these
abscesses, before specific antibiotic sensitivity testing has
been completed. If methicillin resistance is suspected,
vancomycin should be used pending sensitivity testing of
the isolate.

In rare instances when the organisms are resistant to

other antibiotics, quinolones may be effective by virtue

of their satisfactory penetration into the CNS. Pefloxacin

(not available in the United States) and ciprofloxacin
(available in the United States only in oral form) are two
quinolones that may be considered in these cases (114).
There are, however, no clinical data on the utility of

these agents in brain abscesses.

Duration of Antibiotic Treatment

For aerobic bacterial abscesses, six weeks of antibiotics

is advisable, and for anaerobic abscesses, 8 to 16 weeks is
recommended (115). The majority of abscesses are
mixed aerobic-anaerobic infections; intravenous antibi-

otic therapy is recommended for four to eight weeks

(116), and depending on the response, an additional four
to eight weeks of oral therapy may be given. Fungal brain

abscesses require antibiotic therapy for months (116).

Toxoplasma gondii brain abscesses in patients with

AIDS are treated indefinitely (116).

Treatment

Surgical Treatment of Brain Abscesses

Brain abscesses have been treated most commonly by

drainage, aspiration, excision, or a combination of these
methods. Drainage procedures, in which a tube is placed

into the abscess cavity, were the first to be used systemati-
cally (117). Dandy introduced the technique of abscess
aspiration by one or multiple taps through a burr hole

(118), and Clovis Vincent, in the 1930s, advocated exci-
sion via formal craniotomy after encapsulation (119).
Following the introduction of penicillin, LeBeau demon-
strated that areas of cerebritis (unencapsulated ab-

scesses) could be excised (120). Reduction of abscess size
by tapping or drainage in the acute phase, followed by
excision of the residual capsule, was also advocated at
one time (121). Thorotrast, pantopaque, and micro-
paque barium have been used in the past to visualize
abscess cavities so that capsule shrinkage after drainage

or aspiration could be followed on serial skull films.

CNS INFECTIONS / 187

Such markers should not be used when CT scanning is

available for follow-up, because these substances inter-

fere with scan image. One treatment method involves
craniotomy, wide abscess incision, and pus drainage
under direct vision. With this technique, the empty ab-
scess is irrigated with antibiotic solution and left in situ.
In one series, 15 consecutive cures were reported by this
technique with little morbidity (122). However, there

would appear to be no particular benefit of this tech-
nique over the method of needle aspiration (2,75).

The mortality data do not suggest strongly that one

treatment type is inherently better than another. In view
of the fact that the most immediate threats of a brain
abscess are its space-occupying mass and reactive brain

swelling, the primary role of surgical intervention is to

alleviate the increased intracranial pressure. This can be
achieved by any of the methods in current use. Although

the choice is controversial at present, the method is prob-
ably less important than therelief of increased ICP by
any means before irreversible brain damage has occurred
(2,75). Although abscess excision may appear logical be-
cause the brain infection is totally removed, this form of
therapy is usually reserved for patients who have man-

aged to wall off the abscess. Furthermore, patients consid-

ered for abscess excision are more often alert and in satis-
factory neurological condition, indicating a more
optimally functioning brainstem. Brain abscesses con-
taining gas are probably best treated by open craniotomy
and excision if it appears that the abscess is related to a
sinus or mastoid infection or trauma, because the air
may result from a dural tear rather than gas-producing
bacteria. Not only will the abscess have to be excised, but
the dural defect will have to be closed (123). Simpler
procedures such as drainage or aspiration are more often
used with neurologically compromised patients or with
patients who have surgically inaccessible lesions involv-
ing the thalamus, basal ganglia, or brainstem. The seri-

ous disadvantage of drainage or tapping is that a multilo-

cated abscess may be incompletely treated. However, CT
scanning, perhaps with the use of CT/stereotactic guid-
ance, should enable targeting of such multifocal lesions
for needle aspiration. Furthermore, CT scanning can

provide the surgeon with follow-up status of the lesion

with repeated aspiration.

It would seem reasonable to suggest, therefore, that

needle aspiration, with CT/stereotactic guidance, may

be the preferred form of initial management in the fu-
ture. This may be followed by excision if aspiration
should fail. Whatever form of therapy is initially se-
lected, the brain abscess may reaccumulate. It is advis-

able to observe the patient clinically and obtain repeated

follow-up CT brain scans over a period of months and to

manage the patient accordingly.

The surgical treatment of brain abscesses from cya-

notic congenital heart disease has proven especially diffi-
cult. Kagawa and associates (124) treated 17 patients

with this condition by excision following aspiration with
no mortality. Despite their success with aspiration fol-
lowed by excision, they believe that in the future, simple
CT-guided aspiration alone may suffice.

There is no conclusive evidence of any difference in

postoperative seizure frequency following excision ver-
sus tapping or drainage (125,126). Abscesses in the tem-
poral lobe or in the motor/sensory area of the brain are
more likely to lead to the development of seizures than

are lesions involving the frontal or occipital areas.

Although various forms of surgical care may be effec-

tive, the mortality is much lower when patients are in
satisfactory neurological condition, as manifested by
level of consciousness. Mortality doubles, triples, or qua-
druples as the level of consciousness decreases, reflecting
brainstem compromise from uncal or tonsillar hernia-
tion. The obvious conclusion is that for optimal neuro-
logical results, a brain abscess must be treated before it
has caused irreparable brainstem damage consequent to
its mass effect with increased intracranial pressure.

Medical Treatment of Brain Abscess

Past experience has indicated that surgery is the ap-

propriate treatment for brain abscesses. Nevertheless, in

1971, Heineman, Braude, and Osterholm reported the

successful antibiotic treatment of six patients with pre-
sumed brain abscesses (127). Each patient had neurologi-
cal signs and, in some cases, EEG findings suggestive of
localized intracranial infection. Chow and colleagues, in

1975, reported the successful antibiotic treatment of a

patient presumed to have multiple Listeria monocyto-

genes brain abscesses (128). Traditionalists who believed
that pus must be drained or otherwise removed surgi-

cally viewed these reports with some skepticism. Because
no surgical intervention occurred and no histologic speci-
men existed, the possibility remained that these medi-
cally cured "abscesses" were, in reality, areas of cerebri-

tis that antibiotics might be expected to penetrate and
cure. Black, Graybill, and Carache did not have success
with antibiotics alone in the treatment of surgically con-
firmed brain abscesses (108); antibiotics penetrated the
abscesses adequately, yet viable bacteria were subse-
quently cultured from them, possibly because pus inter-
fered with antibiotic activity.

The development of CT scanning made earlier diag-

nosis of brain abscesses more routine, because direct vi-
sualization of the lesion was possible. The course of the
abscess could be followed while antibiotics were admin-
istered, presumably in preparation for surgery. Reports
began to appear on occasion of abscesses cured by antibi-
otics alone (129-136). Computed tomography was used

to diagnose and follow the abscesses in most patients, but

radionuclide imaging was used once. Although these re-

ports appear encouraging, experiments on dogs by Enz-

188 / CHAPTER 10

mann, Britt, and Yeager correlated CT scans with histo-
logic features and indicated that cerebritis may appear
with a peripheral enhancing ring on CT scans and may

be confused with a true abscess (58). Thus, some of the

medical cures of "brain abscesses" may have been cures

of cerebritis instead. This caveat notwithstanding, a
growing number of clinical reports have appeared that
indicate that some brain abscesses diagnosed and fol-
lowed by CT may be cured by antibiotics alone. Petit
reported only 1 death among 14 cases of brain abscess
treated with antibiotics alone (136). Only four of these

patients had abscesses larger than 4 cm in diameter. The

number of medical cures of brain abscesses is low. Fur-

thermore, when medical therapy has been conscien-
tiously tried, it has succeeded only about 60 percent of
the time. Antimicrobials alone are more likely to be suc-
cessful if the abscess is less than 3 cm in diameter and if
antimicrobials are started early (88,137,138).

Rosenblum and coworkers reported successful treat-

ment in 6 of 10 patients with antibiotics alone and sug-

gested that medical management be undertaken for sur-

gically high-risk patients in good neurological status
(137). Such patients include those with congenital heart

disease or multiple or deep-lying abscesses and those

with concurrent meningitis, ependymitis, or hydrocepha-
lus requiring a shunt. A study that investigated 102 pa-
tients with brain abscesses between 1970 and 1986 sug-
gested that although medical therapy is appropriate in a
few patients, surgery remains the definitive approach for
diagnosis and treatment of most brain abscesses (139). In
undertaking the medical treatment of brain abscess, pen-
icillin G and chloramphenicol, with or without gentami-

cin, are started, and periodic CT scans are obtained. Al-
ternatively, initial treatment may consist of a
combination of metronidazole and cefotaxime (or cef-

triaxone or ceftazidime); the combination of metronida-

zole and cefotaxime covers the common causative organ-

isms in brain abscesses and avoids the toxicity of
chloramphenicol and gentamicin (140). After two weeks

of treatment, the patient is rescanned. Surgery is under-
taken if the abscess has enlarged, if significant mass effect

is present, or if neurological deterioration has occurred.
If the clinical course is stable or improving, antibiotics
are continued for two additional weeks. The patient is
rescanned weekly or whenever warranted by new symp-
toms. Surgery is performed if the abscess has not de-
creased in size after four weeks. If the abscess does de-
crease in size with medical management, antibiotics are
continued for six to eight weeks, and CT scans are done

for as long as a year to ensure that the abscess does not
recur. Whalen and Hilal presented a series of 20 brain
abscesses, seven (35%) of which were cured with antibi-

otics and without surgery (141). They argue that two
further criteria should be fulfilled when starting and con-

tinuing the medical management of brain abscesses: (1)
the absence of increased intracranial pressure; and (2) a

good clinical response to medical treatment within the
first week of therapy.

If medical treatment of a brain abscess is to be under-

taken, it is recommended that a neurosurgeon be con-
sulted and that the patient be followed closely in collabo-
ration with a specialist in infectious diseases who is
knowledgeable about available antibiotics and their po-
tential for blood-brain barrier and brain abscess penetra-
tion. Neurosurgical intervention may have to be consid-
ered in the event of clinical deterioration.

Steroids and Brain Abscess

Steroids have been found useful in the treatment of

cerebral edema associated with brain tumors (142,143).
Pyogenic brain abscesses are generally associated with
significant cerebral edema, and there is a question re-

garding use of steroids to control the cerebral edema,
especially because the mass effect of the swollen, edema-
tous brain may contribute to fatal cerebral herniations.
Steroids, however, are known to decrease the immune
response consequent to infection, and the possibility ex-

ists that their use could exacerbate intracranial infec-
tions.

Long and Meachem examined the effect of steroid ad-

ministration upon experimental brain abscess encapsu-

lation (144). They concluded that dexamethasone may

retard but not eliminate abscess capsule formation.
Quartey, Johnson, and Rozdilsky also examined the ef-
fect of glucocorticoids on experimental brain abscesses
histologically and determined that steroids did indeed

retard capsule formation, but they noted less edema of

the adjacent tissue (145). Thus, steroids showed two op-

posing effects. Reduction of surrounding edema was

beneficial, but retardation of capsule formation was dele-
terious because viable bacteria remained in the brain.

Wallenfang, Bohl, and Kretzschmar used an experimen-

tal cat model to assess physiologically and histologically

the problem of abscess encapsulation, associated brain

edema, and the effects of steroid administration (146).
Steroids (0.5 mg dexamethasone/kg) markedly amelior-
ated brain edema in adjacent and distal brain. Abscess
encapsulation was observed, but cats treated with antibi-

otics and glucocorticoids exhibited a weaker formation
of the mesenchymal inflammatory infiltration (59).
Lyons and associates studied the effect of short-term,
high-dose corticosteroids on CT enhancement of experi-
mental brain abscesses and concluded that the use of

high-dose (1.2 mg/kg), short-term (12 hour) corticoste-

roids did not appear to alter significantly the evolution of

intracranial abscess. Histologically, however, they did

observe "some changes" in the amount of collagen depo-
sition (147). Nevertheless, these investigators could not
ascertain whether the high-dose, short-term steroid ad-
ministration hindered capsule formation. Enzmann and

CNS INFECTIONS / 189

colleagues studied the effect of dexamethasone (1.8 mg/
kg) given over 48 hours on the encapsulation of experi-

mental brain abscesses. These authors concluded that a
"48-hour course of steroid administration had no notice-
able effect on histology of experimental brain abscesses,
either in the cerebritis or capsule stage" (63).

In the clinical setting, the use of steroids in the treat-

ment of brain abscess is controversial (148); some avoid
their use for fear of decreasing the inflammatory re-
sponse and hindering encapsulation (145), but others be-
lieve that steroids are beneficial (149,150). CT scanning
may allow each case to be individualized. If surrounding

brain edema is severe and poses a risk of neurological
deterioration, steroids (along with prompt surgical treat-

ment) are recommended because, experimentally, they
have been shown to reduce the edema associated with

the abscess. It has been suggested that the use of steroids
is reasonable when the pathogen is known and specific
antibiotic therapy is given concurrently (2,75). If, on the
other hand, the abscess is relatively small (less than 3 cm)
and is not associated with brain edema, antibiotics may
be given without steroids.

Current Mortality Associated with Brain Abscess

In the early part of the antibiotic era, the mortality

associated with brain abscess remained surprisingly high.
In some series, lower mortality was achieved by aggres-
sive diagnosis, timely surgery, close postoperative sur-
veillance, and improved antibiotic usage (1,151,152).
From 1946 to 1977, surgical mortality ranged from 20 to
60 percent. Introduction of CT scanning of the brain in

the mid 1970s provided a means of earlier diagnosis;

Rosenblum and associates attributed 0 percent mortality

in their series to this new diagnostic modality (153). A
similar series showed a mortality of 20 percent among 15

cases in which CT scans were used; of the three deaths,

two followed antibiotic therapy alone and one followed
combined antibiotic and surgical management (154).
On the other hand, Dohrmann and Elrick observed that
the advent of CT scanning had no apparent effect on
brain abscess mortality (29). It would appear that, apart
from early diagnosis and possible surgery, the identifica-

tion of the offending organism and selection of appro-

priate antibiotics are of paramount importance in reduc-

ing mortality and morbidity (2). The information

provided by the CT scan regarding the status of the ab-

scess and the surrounding brain does offer the neurosurg-
eon and other involved clinicians greater latitude in man-
agement in deciding whether to pursue a vigorous course
of antibiotic therapy, to tap, drain, or excise the abscess,
or to tap and allow further encapsulation before later
excision. If CT scanning is unavailable, clinical judg-
ment plus the relatively accurate diagnostic modalities of
EEG, radionuclide scanning, angiography, and ultra-

sound in infants should permit early diagnosis and de-

creased mortality.

Sequelae of Management

Gruszkiewicz and associates reported a 12 percent in-

cidence of neurological sequelae—hemiparesis, seizures,
hemianopsia, and aphasia—among 50 survivors (155).
In Nielsen's series, only one-third of 67 patients showed
complete neurological recovery (156).

In another series, 15 to 30 percent of survivors had

paresis, and 10 to 20 percent had varying degrees of
speech and language defects (157). As expected, parietal
abscesses are more prone to be associated with such defi-
cits (156). Some postabscess disability may be expected
in 30 to 50 percent of all patients, whereas total disability
occurs in 7 to 17 percent (125,157). The quality of sur-
vival may be poorer in children (50,157). Nielsen ob-
served that 29 percent of children, but only 9 percent of
adults, had severe epilepsy and that 33 percent of chil-

dren, but only 13 percent of adults, demonstrated intel-
lectual reduction following a brain abscess (156). Hirsch
and colleagues, on the other hand, found that almost
three-quarters of children who survived their brain ab-
scesses were essentially normal (158).

Seizures occur in 15 to 55 percent of survivors, but up

to 73 percent may report seizures if they are followed up

for long periods (126,159). Frontal and temporal ab-

scesses are more frequently associated with epilepsy

(156). In some series, seizure development was indepen-
dent of the mode of surgical therapy (125,157), but in
one review, aspiration of the abscess had less of an associ-

ation with late epilepsy (156). Postabscess epilepsy has its

peak incidence four to five years after abscess occurrence
and treatment and may lead to death in a small percent-
age of those who survive their abscess. Because of this,
anticonvulsants should be continued for five years after
successful brain abscess therapy. Despite the large num-
ber of drugs available, medical control of epilepsy fails in
about 25 percent of cases (156).

With respect to cerebellar abscess, neurological se-

quelae following successful treatment may be minimal
(5,35,160).

Actinomycosis (161-165)

Actinomycosis is a noncontagious, suppurative, bacte-

rial infection characterized by chronic inflammatory in-
duration, sinus tract formation, fever, and leukocytosis.

Actinomyces israelii is responsible for the majority of

human actinomycotic infections. Once known as the
"ray fungus," A. israelii is now recognized as a gram-
positive, non-acid-fast anaerobic eubacterium, interme-
diate between classical bacteria and higher fungi. Unlike
Nocardia, Actinomyces have not been isolated from the

190

CHAPTER 10

soil. The bacteria reside in natural cavities of humans
and animals, particularly in the mouth. The endogenous
organism gains entry to the body via breaks in the mu-
cous membranes. Involvement of the CNS (1 to 15 per-

cent of cases) occurs by hematogenous spread from a

pulmonary focus or by direct spread from lesions involv-
ing the skull, face, and throat, possibly via lymphatics.
Aciinomycetales streptomyces brain abscesses in AIDS
patients have been reported.

Signs and symptoms of an actinomycotic brain ab-

scess depend upon location and may include focal neuro-

logical findings as well as increased intracranial pressure.

Actinomycotic brain abscess occurs more often than
meningitis and subdural empyema caused by that organ-
ism. Specific diagnosis can be made by the demonstra-
tion of basophilic or amphophilic "sulfur granules" on
microscopic examination of tissue exudates. The organ-
isms are not visible on hematoxylm and eosin sections

but may be seen with the Gomori stain. The organisms
grow anaerobically.

Surgical aspiration or excision plus penicillin, 2 to 20

million units per day for 6 to 18 months, forms the basis
of treatment. A 28 percent mortality has been reported
in cases adequately treated with antibiotics and surgery.

Poor prognosis is related to an interval of greater than

two months before diagnosis and treatment.

Nocardiosis (166-170)

Nocardia are strictly aerobic, gram-positive filamen-

tous bacteria with an unusual propensity to spread from

a primary pulmonary focus to the brain. The most com-

mon species to infect humans is Nocardia asteroides.

CNS involvement, usually as a parenchymal abscess or,
uncommonly, as a leptomeningitis, occurs in 20 to 30

percent of patients with nocardia. A case of nocardia

abscesses complicated by a mycotic (infected) cerebral
artery aneurysm has been reported. In the United States,
75 percent of nocardial infections occur in immunocom-

promised persons. The overall mortality of cerebral no-

cardiosis is 80 percent, largely because this disease occurs
in people with serious underlying disease (e.g., AIDS pa-
tients and patients with immunosuppression associated
with malignancies or following treatment for organ
transplantation).

For nocardia brain abscesses, surgical aspiration or ex-

cision, combined with antimicrobial therapy, forms the
basis of treatment. Sulphonamides are the drug of

choice: this treatment should be continued for at least

one year. Good prognostic predictors in cerebral nocar-

diosis include early diagnosis, appropriate chemother-

apy, limited brain involvement, and, most importantly,

the absence of serious underlying disease. At least one

case of cerebral nocardia brain abscess has been suc-

cessfully treated medically, using CT to follow abscess
resolution.

Multiple Brain Abscesses

Before 1975 the incidence of multiple brain abscesses

reported in various series ranged from 4 to 13 percent.
Since the advent of CT brain imaging, the reported inci-

dence of multiple brain abscesses has increased to 50
percent. Earlier diagnosis and better antibiotic therapy
have improved the prognosis of these lesions.

Rousseaux and associates reported on a series of 12

patients who had multiple (two to six) intracranial ab-

scesses whose diameters ranged from 0.5 to 5.0 cm with
an average diameter 1.7 cm (171). The causative organ-
ism was identified in only three cases. These patients
were treated vigorously with intravenous ampicillin, tri-

methoprimsulfamethoxazole, and sometimes with an
aminoglycoside such as gentamycin, sisomycin, or to-
bramycin administered intramuscularly. Treatment was
continued for about three months. The patients were

monitored for bone marrow depression, renal toxicity,
and cutaneous allergic phenomena. If needed, steroids

or mannitol treatments were given initially to combat
associated edema. Response to therapy was provided by
serial CT scans. In this scries, only two patients required

surgery, and both survived. One patient treated with anti-

biotics alone eventually died, giving a 10 percent mortal-
ity for the 10 persons treated without surgery.

During the three-year interval of their study, only two

instances of misdiagnosis by CT were made. In both of

those cases, repeated CT scanning and lack of response

to treatment indicated that the multiple lesions were tu-

mors. Appropriate surgical therapy was then under-
taken.

Boom and Tuazon also have reported the successful

antibiotic treatment of seven patients harboring 2 to 10

brain abscesses each (172). Surgical treatment of these
lesions was not considered because of their multiplicity

and inaccessibility. A variety of antibiotics was used in

these cases: nafcillin, dicloxacillin, chloramphenicol,
penicillin G, PenV K, and rifampin. They used intrave-
nous antimicrobial treatment for about two months and
then continued oral therapy for several more months.

The patients' progress was followed by means of CT

scanning.

These investigators concluded that high doses of anti-

biotics for an extended period may represent an alterna-
tive approach in cases of multiple and inaccessible brain

abscesses. For this form of therapy to succeed, an early

response to antibiotics must occur, and follow-up CT

scans must be obtained. An early effort at making a mi-

crobiological diagnosis is important to plan optimal anti-

biotic therapy; CT-guided needle aspiration may be the

CNS INFECTIONS / 191

key to diagnosis. Despite their success in this limited se-
ries, the authors reiterated the fact that surgical evacua-
tion of pus remains essential for most brain abscesses.

Subdural Abscess and Empyema

Subdural infection accounts for approximately 10 to

32 percent of all brain abscesses. The incidence of this

condition may be higher in developing countries

(3,17,63). Pus in the subdural space can be localized (ab-

scess) or diffuse (empyema). In approximately 50 per-
cent of cases, the subdural pus occurs as an empyema
spread widely over a hemisphere (Fig. 2). In the remain-
ing half, the pus is loculated as a hemispheral convexity
mass (30 percent), in the interhemispheric fissure (10
percent), or in the posterior fossa (10 percent). Acute

frontal sinusitis and chronic mastoid infections are the

two most common antecedent causes. Chronic otitis me-

FIG. 2. CT scan showing right subdural empyema in a 64-
year-old woman admitted with sudden onset of generalized
seizures. She had low-grade fever and right hemiparesis, and
the peripheral white blood cell count was 19,700. With a ten-
tative diagnosis of chronic subdural hematoma, she was
taken to the operating room, and burr holes were made; there
was an unexpected free flow of grossly purulent material
from the subdural space. A craniotomy flap was then turned
for removal of a thick yellow membrane on the cortical sur-
face. Microbiological studies were negative. The patient was
placed on broad-spectrum antibiotics, and she recovered
after a prolonged hospital course. There was no antecedent
history suggesting the source of the infection, although she
had a history of chronic obstructive pulmonary disease and
an episode of bronchopneumonia one month prior to her ad-
mission. The subdural collection in this non-enhanced CT
scan covers much of the convexity of the right hemispheres
(arrows); the cortical markings on that side are diminished.

dia is particularly likely to be the underlying cause of the

empyema in developing countries such as India and Sri

Lanka (173). The infecting bacteria may spread in a con-
tiguous fashion from the infected sinus or bone through

the adjacent dura and into the subdural space or may

spread from the infected sinus to emissary veins that
connect with subdural veins. A septic thrombosis form-
ing in a cortical vein creates a nidus of infection that
spreads in the subdural compartment in which the pus
can spread freely (123,174,175). Subdural empyema also
may occur as a consequence of trauma, cavernous sinus

thrombosis, scalp infection, or infected cephalohema-
toma. In addition, a preexisting subdural hematoma
may become infected as a result of concomitant sepsis or
iatrogenically from needle aspirations. Subdural em-
pyema was reported in 2 percent of patients following

the treatment of meningitis (176). Subdural empyema

may complicate a subdural-peritoneal shunt as in the

case of perforation of the bowel by the peritoneal end of
the shunt catheter (177). Another unusual source of sub-
dural infection is that associated with the pins penetrat-
ing the skull for halo immobilization of the neck (178).

Bacteriology

In a series of 66 patients with a subdural empyema,

aerobic or anaerobic streptococci were the infective
agents in 37 cases and staphylococci in six (179). Yoshi-

kawa, Chow, and Guze reviewed the bacteriological find-

ings of subdural empyemas and found that the most
common organisms were aerobic streptococci and staph-
ylococci (180). Salmonella is among the uncommon of-
fending organisms in subdural empyema; in children,
salmonella infection of the CNS more commonly takes

the form of a subdural empyema, but in adults it is more

often found in the form of a brain abscess (181). Twelve
percent of cases were caused by anaerobic organisms,

and 27 percent of the cultures were "sterile." If "sterile"

cultures are assumed to be largely composed of inade-
quately cultured, anaerobic organisms, then about 40
percent of subdural infections may be caused by anaer-
obes. Khan and Griebel confirmed these bacteriological
findings (182). Posttraumatic and postoperative sub-
dural empyemas, however, were caused by Staphylococ-
cus aureus or Staphylococcus epidermidis.

Clinical Manifestations

Subdural infection occurs more often in males. Local

infection in the region of the affected sinus, scalp, or

skull may be evident early, but infection within the sub-
dural space is heralded by intense generalized headache,

fever, drowsiness, meningeal signs, and focal neurologi-

192 / CHAPTER 10

cal findings such as Jacksonian seizures, aphasia, or he-

miparesis. Interhemispheric pus often produces a contra-

lateral lower monoparesis because it involves the medial

portion of the motor strip. Evidence of elevated intracra-

nial pressure (drowsiness, papilledema, nausea, and vom-
iting) may also occur. Subdural empyema as a complica-
tion of sinusitis may be misdiagnosed as aseptic
meningitis or viral encephalitis. Subdural infection is
usually less fulminant than bacterial meningitis but
more rapidly progressive than a brain abscess. In bacte-

rial meningitis, focal signs are less common, and preced-
ing sinus or mastoid infection need not be present. Clini-
cally, differentiating between subdural infection and
brain abscess may be difficult. Subdural abscess and

brain abscess may be present concomitantly but, for un-
known reasons, this is rare.

Laboratory Findings

Peripheral leukocytosis with a left shift is usual. The

erythrocyte sedimentation rate (ESR) is usually elevated.
In the series of Khan and Griebel, EEG was performed in

12 of 15 patients with subdural empyema, and in 10,

there was generalized or unilateral slow-wave activity or
unilateral voltage suppression (182). In a study of EEG
in the diagnosis of subdural empyema, the combination
of focal theta waves, unilateral depression of cortical ac-
tivity, and diffuse slowing of background activity has
been regarded as being characteristic for subdural em-
pyema and may be more sensitive than CT scanning
(183). Early in the course of the disease, CSF findings
may be normal. Later, varying degrees of pleocytosis oc-
cur, the protein content increases, and the spinal fluid

glucose level remains near normal. The CSF remains
sterile unless there is an associated meningitis. Because

subdural empyema produces an intracranial mass, there
is risk that herniation and death may follow lumbar

puncture. Therefore, lumbar puncture should generally
be deferred in patients with meningitic symptoms and
focal neurological signs until subdural (or brain) abscess

has been excluded by CT or MRI scanning or angiogra-

phy (2,75,184).

Radiological Studies

Roentgenograms in patients with a subdural em-

pyema often suggest sinus or mastoid infection. Osteo-
myelitis may be seen about an involved sinus. If osteo-
myelitis of the cranial vault is the underlying source of
subdural infection, it may be evident on skull films. In
view of the frequent association of subdural empyema

with paranasal sinus disease, plain x-rays of the skull and

sinuses should be obtained, especially because the initial

CT scan may be normal (185).

Danziger analyzed 11,300 CT scans in South Africa

and observed 23 (0.2 percent) cases of subdural em-
pyema (6). On CT, a subdural empyema usually appears

as a cresenteric lesion at the periphery of the brain. En-
hancement may demonstrate a rim adjacent to the cor-
tex, and this rim may thicken with time. The ipsilateral
ventricle may be displaced. This rim may be thicker with
chronic processes. Cerebral edema is not a prominent
feature. CT scanning may fail to help in diagnosing sub-
dural empyema, presumably because, at some evolu-

tionary stage in its development, the combination of
brain and pus is isodense (60,186). A CT scan showing

unilateral subdural empyema is shown in Figure 2. The

incidence of false negative CT scans may be reduced by
routine use of contrast-enhanced CT in suspected cases
and, where feasible, the use of high-resolution scan-

ners (187).

MRI has been reported as being superior to CT in

identifying the presence and extent of subdural empye-

mas and in distinguishing empyema from chronic sub-

dural hematomas (188). Coronal MRI scanning may
demonstrate subtemporal extension of the empyema
(67). In some instances, RN scans may reveal the em-

pyema (184,189) and cerebral angiography will also re-

veal the pus collection (190). In patients with subdural
collections complicating hemophilus influenza meningi-
tis, CT scanning is not reliable in distinguishing sterile
effusions from infected collections (empyema) (191).
The accuracy of CT scanning is increased when com-

bined with examination of Hemophilus influenzae cap-
sular antigen; this combination of diagnostic modalities
accurately predicts if the subdural collection is infected
or is likely to become infected (191).

In the past, ventriculography was used to diagnose pos-

terior fossa empyema; however, air studies are no longer
considered useful diagnostic modalities when high reso-
lution CT or MRI scanning is available.

Pathophysiology

Several pathophysiological processes may be responsi-

ble for the rapid clinical deterioration seen in cases of

subdural empyema. Bacterial metabolic products or tox-

ins may adversely affect neural-glial function. BBB

breakdown may cause cerebral edema. Cortical vein

thrombosis may lead to associated cerebral hemisphere
infarction, and, finally, the mass of the subdural collec-
tion may lead to cerebral herniation (192).

Treatment

Subdural empyema represents a neurosurgical emer-

gency. Early drainage is essential because antibiotics

CNS INFECTIONS / 193

may not eradicate the infection. The rapid accumulation
of subdural pus can dangerously increase intracranial
pressure. Once the diagnosis is suspected, large doses of
broad-spectrum antibiotics (such as a combination of

penicillin G, chloramphenicol, and nafcillin) should be
started, and the patient should be prepared for surgery.
Some surgeons drain the pus via multiple burr holes
placed over the involved area, but others prefer limited
craniectomies or even large craniotomy flaps to allow
wide exposure of the subdural infection. Bannister, Wil-
liams, and Smith recommend a wide craniotomy; of 66
patients in their series, 14 of 27 patients treated by burr
holes died, but only 5 of 35 died after craniotomy (179).
Several series have reported that later craniotomy was

needed for some patients initially treated by burr holes

(173,184). Areas of subdural abscess are copiously irri-

gated with such antibiotic solutions as bacitracin (or gen-
tamycin). It is crucial that a specimen of the pus be ob-
tained for gram-stain and culture for aerobic, anaerobic,

fungal, and mycobacterial organisms to aid in selection

of antibiotics.

When an interhemispheric subdural abscess is sus-

pected, the patient's head should be draped so that trephi-
nations or craniectomy can be performed parasagittally
from front to back and the entire interhemispheric re-

gion may be inspected, drained, and irrigated with antibi-

otic solution. Any undetected, undrained pus pockets
may lead to persistence of the intracranial infection. Pos-

terior fossa subdural empyema either is otogenic in ori-
gin or has spread from supratentorial subdural em-
pyema. The diagnosis may be delayed, even with the aid
of the new imaging techniques. Posterior fossa craniec-
tomy is recommended as the operation of choice, in pref-
erence to posterior fossa burr holes (193).

In the management of subdural fluid collection in in-

fant Hemophilus influenzas meningitis, Curless has re-
ported that subdural taps and systemic antibiotics are
usually effective (194). Another option is burr hole and
catheter drainage, along with antibiotic therapy (195).
Although the consensus among most authors favors ag-
gressive surgical evacuation of subdural intracranial em-
pyemas, a minority viewpoint advocates treatment with
antibiotics and without surgery (196). The authors who
take the latter view emphasize the use of CT for diagno-
sis and follow up during the course of antibiotic treat-
ment.

The primary focus of infection leading to the subdural

suppuration also must be vigorously treated. When os-
teomyelitis of the frontal sinus is present, the infected
bone should be removed and the frontal sinus exenter-
ated. If the skull and inner sinus wall appear intact, the
involved sinus should be drained. Surgery for sinus, mid-

dle ear, or mastoid infection can be performed electively
(197), or it can be done simultaneously with the evacua-

tion of the subdural empyema.

Prognosis

Prior to the use of antibiotics, subdural empyemas

were usually lethal (197), but mortality has now declined
to 18 to 20 percent (198). As with brain abscesses, mortal-
ity from subdural empyema increases with neurological
deterioration, and for the same reasons (182,184). Bilat-
eral spread of pus is a common cause of mortality. Early
diagnosis and bacteriological study for selection of
proper antibiotics are likely to reduce the mortality. Sur-
vivors may be neurologically intact, but focal neurologi-
cal deficits, such as hemiparesis or dysphasia, are com-
mon. Seizures occur in one-fourth to one-third of
survivors but may be controlled by anticonvulsant medi-
cation (182). Calliauw, dePraetere, and Verbeke fol-
lowed 18 patients with subdural empyema more than
five years after successful surgical therapy (199). None

developed seizures after the second year following sur-
gery. Therefore, anticonvulsants should be given for ap-
proximately two years after successful treatment of a
subdural empyema. A similar experience was reported
by Cowie and Williams (192).

Intracranial Tuberculoma

Tuberculosis of the central nervous system may dam-

age the brain in many ways. A dense basal exudate may
form, which may obstruct CSF flow. Extension of this
basal exudate into the brain parenchyma itself may

cause a border-zone encephalitis. Multiple small foci of

ischemia may occur consequent to vasculitis involving

many small blood vessels. Infiltration of the meningeal

exudate into the walls of larger, basilar blood vessels may
cause brainstem infarcts. Intracranial tuberculomas may
form that act as both mass and inflammatory lesions
with accompanying edema. The pathological changes in
and around the reactive border zone of tuberculomas
has suggested a delayed type of hypersensitivity to tuber-
culoprotein, which is thought to initiate the "chain of
immunologic responses" (200). Occasionally, a more
acute form of brain edema develops with a diffuse, peri-
vascular loss of myelin as an allergic hypersensitivity re-
action to tuberculoprotein or to the brain's myelin basi

protein (201).

The incidence of focal tuberculous infection of the

brain—intracranial tuberculoma—varies according to
the prevalence of tuberculosis in the community. Al-
though intracranial tuberculosis is extremely common
in developing countries, epidemiologic data from devel-
oped countries are scarce: 89 tuberculomas were found
in 13,000 autopsies (0.68 percent) in Leeds, England

(1933) (202), whereas 43 were discovered during 15,000
postmortem exams (0.29 percent) in Los Angeles (1938)

(203). Thus, physicians in developed countries may fail

194 / CHAPTER 10

to recognize the disease because of its rarity. Tuberculo-
sis may be quite prevalent among immigrants from devel-
oping areas who come to developed countries (204). Ac-
cording to reports from countries where intracranial
tuberculomas are common, 32 to 50 percent of patients
with intracranial tuberculomas are younger than 10
years of age, and approximately 85 percent are younger
than 25 (201,205,206). Tuberculomas may occur any-
where in the brain, but infected children have a high
incidence of infratentorial lesions.

Pathology

Grossly, a mature tuberculoma is a well-defined, avas-

cular mass with multiple nodular extensions and a yel-
lowish, gritty, caseating central core. In its immature
form, the lesion consists of multiple small tubercles with
caseating or cystic centers surrounded by edematous
brain. More than half are adherent to the dura. Micro-

scopically, the central core of caseous necrosis is

surrounded by tuberculous granulation tissue consisting
of epithelioid cells, Langhans' giant cells, lymphocytes,
polymorphonuclear cells, and plasma cells. Acid-fast ba-
cilli may be seen in either layer. The surrounding brain

shows degenerated nerve cells and fibers, swollen astro-

cytes, and oligodendroglia, as well as thrombosed vessels
and multiple microinfarcts. Rarely, frank tuberculous

abscess resembling a pyogenic abscess may occur

(207,208). Several cystic tuberculomas resembling glio-

mas have also been observed (201,206).

Clinical Manifestations and Diagnosis (209,210)

Patients with intracranial tuberculomas usually have

evidence of the disease elsewhere or have had tuberculo-

sis. Fever of a few weeks' duration usually precedes the
onset of neurologic findings, which will vary according

to tuberculoma location. Seizures often occur with su-

pratentorial lesions. Children often have evidence of a

posterior fossa mass: headaches, nausea, vomiting, pa-
pilledema, nystagmus, ataxia, and separated cranial su-
tures or an enlarging head. Unusual presentations of tu-
berculomas include scalp swelling, a draining sinus, CSF

rhinorrhea, exophthalmos, trigeminal neuralgia, or evi-
dence of a pituitary or acoustic nerve "tumor" (201).

Intracranial tuberculomas can be diagnosed with a fair

degree of precision by CT, especially in geographic areas

where tuberculosis is endemic. The CT appearance of

intracranial tuberculomas has been classified as (1) small

discs and rings measuring less than 1 cm in diameter
with marked contrast enhancement and surrounding

low-attenuation edema; (2) large rings lacking the low

central lucency of pyogenic abscesses (a central nidus—

, the so-called "target sign"—may be present); or (3) a
rlarge, ball-shaped nodular mass with irregular contours

(211). The lesions may be solitary or multiple. Although

CT scanning is the ideal diagnostic procedure, it may be

unavailable in developing nations where intracranial tu-
berculomas are iriost common (212). When CT or MRI
scanning is not available, plain skull x-rays, electroen-
cephalography, RN scans, angiography, and ventriculo-
graphy are still useful. In general, 2 to 6 percent of intra-

cranial tuberculomas calcify, but among Eskimos and

North American Indians, 60 percent of the lesions show
calcification (201).

Angiographically, a tuberculoma presents as an avas-

cular mass. Vessels in the vicinity may show a reduced
caliber, and the midline shift may be small relative to the

size of the lesion. Tuberculomas near the surface may
occasionally show a blush from meningeal or cortical
vessels.

Treatment

Until the advent of CT scanning, surgical resection of

intracranial space-occupying lesions caused by tubercu-
lomas was the preferred treatment. Before the develop-
ment of effective antituberculous chemotherapy, surgi-

cal resection of these lesions carried a mortality of up to

85 percent from subsequent tuberculous meningitis
(205). Total excision of the tuberculoma is preferred, but
partial excision may be done when large tuberculomas
impinge upon vital structures such as the brainstem
(205,206,213). In such cases, a rim of tuberculoma may
be left adjacent to the brain.

Following the development of effective drug therapy,

operative mortality for intracranial tuberculoma resec-
tion fell to about 14 percent, and the incidence of fatal,
postoperative tuberculous meningitis fell to 6 percent.
Although total excision of the lesion is preferred, partial
removal has been advised when large tuberculomas im-
pinge on vital structures (201,205,206,210). In such
cases, it is advisable to treat the residual lesion with anti-
tuberculous drugs. Various combinations of rifampin,
streptomycin, para-amino-salicylic acid, and isoniazid

are used pre- and postoperatively.

Paralleling the development of nonoperative treat-

ment for pyogenic brain abscesses, an initial nonopera-
tive approach for the treatment of intracranial tubercu-
lomas has emerged. This has been possible with the
advent of CT and MRI scanning for follow up. Antitu-
berculous drug therapy alone may be curative, especially
for small lesions. A therapeutic trial on antituberculous
medication is a reasonable approach. CT-guided biopsy
for histology and culture may be carried out for confir-
mation. Surgical resection may be required to reduce

intracranial pressure in the case of large lesions.

In 1983, Harder, Al-Kawi, and Carney reported on a

series of 20 patients with intracranial tuberculomas

(214). Ten patients were treated surgically, and 10 were
treated with antituberculous drugs alone. The progress

CNS INFECTIONS / 195

of the medically treated patients was followed serially by

CT scanning. No patients died in either group, but the

functional state of those treated medically was signifi-

cantly better than those who had surgery as their primary

therapy.

Tandon and Bhargava reported their experience with

50 patients with intracranial tuberculomas (211). In

these patients, neither vision nor life was threatened by

severe intracranial hypertension. All were treated pri-

marily with antituberculous medication, and serial CT

scans were obtained to follow their progress. The authors

divided their cases into three groups: (1) patients with
lesions larger than 1 cm; (2) those with multiple ring or

disc lesions less than 1 cm in diameter; and (3) patients
with solitary ring or disc lesions less than 1 cm in diame-

ter. This study clearly showed that most intracranial tu-
berculomas resolve under medical management.

In conclusion, it seems that CT scan or CT scan plus

angiography can provide a high level of diagnostic confi-
dence with regard to intracranial tuberculomas. If intra-
cranial tuberculoma is suspected, intensive antitubercu-
lous therapy should be started and continued for two

weeks. Serial CT scans are obtained to follow the course

of treatment, which is continued for at least 12 months.

If the nature of the lesion is in doubt, either a therapeu-

tic trial of antituberculous drugs is initiated or biopsy

(stcrcotaxic or open) is obtained. If there is biopsy confir-
mation of tuberculoma, it is generally not necessary to

excise the lesion, and reliance is placed on antitubercu-

lous drugs to optimize long-term neurological function.

Patients with large tuberculomas, with signs of raised

intracranial pressure threatening vision or life, may re-
quire surgical excision of the lesion before starting medi-
cal treatment. However, if intracranial pressure is not
severely elevated, or if visual loss is not threatened, pa-

tients suspected of having intracranial tuberculomas can

be given a trial of medical therapy. Surgery can be re-
served for nonresponders. Papilledema without a serious
loss of vision is not considered a contraindication to med-
ical treatment (215-217).

Steroids may be used when cerebral edema is severe

without fear of exacerbating the intracranial tubercu-
loma. provided that antituberculous therapy is given con-

currently. Isoniazid, ethambutol, and rifampin in recom-

mended doses provide adequate coverage.

Intracranial tuberculous lesions may paradoxically

enlarge during antituberculous therapy, and resolution

of the tuberculous lesion demonstrated on CT may take

up to a year (218).

If CSF pathways are blocked, a shunt procedure may

be required (219).

Herpes Simplex Encephalitis (HSE)

Herpes is probably the most frequent cause of spo-

radic, viral infection with severe neurological sequelae in

temperate climates, including the United States (220-
223). The occurrence rate is believed to be about 2 cases
per million population per year (224). The virus infects
the nasal mucosa and nasopharynx and penetrates the
CNS through the cribiform plate (225). Pathologically,
perivascular lymphocytic infiltration is seen, along with

severe necrosis of the medial temporal and orbital fron-

tal lobes. Other areas in the brain are less often involved
(226). Type A Cowdry eosinophilic inclusions are seen

in both neurons and glia (227). Electron microscopy

demonstrates herpes virus particles within affected cells
(220). Often, severe temporal lobe swelling accompanies
the infection and may cause a significant intracranial
mass lesion that may have to be removed surgically.

Clinical Manifestations and Diagnosis

Clinically, HSE is manifested by headache, drowsi-

ness, fever, seizures, and focal neurological signs. Men-
ingeal signs are not prominent. These nonspecific find-
ings may be seen with many types of encephalitis, but
herpes infection is characterized by prominent psycho-
logical symptoms early in the disease (global confusion,
disorientation. clouding of consciousness, and hallucina-

tions, particularly olfactory and gustatory), because of
temporal lobe involvement (227). Early diagnosis of

herpes is vital because, untreated, the disease has a high
mortality and may be associated with severe neurologi-

cal sequelae in survivors. EEG usually shows temporal
high-voltage sharp waves. RN scanning is characterized

by unilateral or bilateral areas of hyperperfusion with

focal uptake on the static images. When bilateral, this
strongly suggests HSE (60). After the disease is estab-
lished, CT scans reveal a low-density area, usually in the
medial temporal lobe, unilaterally or bilaterally. There is

an irregular pattern of contrast enhancement. These

three neurodiagnostic modalities are positive in about 80
percent of cases (228). MRI scanning is more sensitive

than CT in detecting early changes. Petechial hemor-

rhages, in particular, which are commonly seen patholog-

ically in HSE, may not be detected on CT scanning, but
they are readily seen on MRI scanning, thereby improv-
ing diagnostic specificity (67). Failures probably relate to
the stages of the disease at which the tests are performed.
Fluorescent antibodies of the herpes virus antigen and a
passive hemagglutinating antibody may be demon-
strated in the cerebrospinal fluid.

Treatment

In the late 1970s, mortality of biopsy-proven HSE was

shown to be more than 70 percent (229), and neurologi-
cal sequelae were noted to be severe among survivors
(229-232). Adenine arabinoside (Ara-A, vidarabine) was

196 / CHAPTER 10

found to be a fairly effective antiviral agent for the treat-
ment of HSE, reducing mortality to about 47 percent
(232). After the original report of Whitley and associates

showed the efficacy of vidarabine (232), a subsequent

study raised questions about the usefulness of this drug
(233). However, further uncontrolled studies by Whit-
ley's group supported vidarabine (228,234), though the
mortality of HSE still approximated 50 percent with the
use of the drug.

In 1984, Skoldenberg and colleagues studied 51 pa-

tients with HSE to compare the effectiveness of vidara-
bine with acyclovir, a purine nucleoside analogue (224).
Acyclovir appeared distinctly more effective than vidar-
abine, but factors such as level of consciousness, age of
patient, and absence of brain biopsies to prove abso-
lutely that each patient had HSE could have affected the

results. A subsequent study was therefore undertaken by

Whitley and colleagues to compare acyclovir efficacy
with vidarabine (228). Their results indicated the superi-
ority of acyclovir in terms of mortality. Survival was

found to be influenced by patient age, level of conscious-

ness; and duration of disease before the start of therapy.
Even with statistical adjustments to account for these

factors, however, acyclovir was seen to be the superior

drug for reducing HSE mortality.

With both drugs, survival and return to normal func-

tion have been positively correlated with adequacy of

neurological function. Acyclovir treatment must be

started as soon as possible when HSE is suspected. Whit-
ley's group, in particular, believes that brain biopsy is
mandatory to confirm the diagnosis (232). The biopsy
can be carried out with CT guidance (235). Brain biopsy

may reveal conditions other than HSE, such as tubercu-
lous and cryptococcal meningitis or subdural empyema.

The risk to the operating team in obtaining a biopsy in

such patients is thought to be minimal (236). Biopsy is

also recommended in infants and children with sus-
pected herpes simplex virus encephalitis (237). If one
suspects HSE. acyclovir should be started before brain

biopsy is obtained. Side effects from acyclovir have, thus

far, been minimal, so the drug may be safely continued
while awaiting HSE viral cultures. If the herpes virus is
isolated, drug therapy is continued for 10 days. Because
acyclovir is nontoxic, one may make a cogent argument
for continuing the drug a full 10 days in the face of nega-

tive HSE viral cultures because brain biopsy may miss

the herpes focus 25 percent of the time (225).

Despite the safety of antiviral drug therapy, brain

biopsy has been recommended in patients with possible

HSE (238). These authors state that the rationale is not

to confirm HSE but rather to rule out other treatable
conditions. Such conditions may be suspected in pa-
tients with low CSF glucose, raising suspicion of infec-
tions such as tuberculosis, brain abscess, toxoplasmosis,

or cryptococcosis.

Parasitic Brain Abscess

Cysticercosis

Life cycle

Humans are the definitive host for the pork tape-

worm, Taenia solium. The adult form of the tapeworm
lives in the human small intestine. The pig itself becomes

infected with the parasite by eating ova or gravid worm
segments from human excretia. Once the pig ingests the
ova, the surrounding capsule is digested away and the
contained larvae penetrate the pig's stomach mucosa
and are disseminated widely in the animal's body. Hu-
mans, after ingesting infested pork, develop a mature

tapeworm in the small intestine. Humans can harbor not

only the mature tapeworm but also the larval form. Vom-
iting or reverse peristalsis delivers proglottids from the
small intestine to the stomach (239-241). In humans,

once the larvae penetrate the gastric mucosa, dissemina-

tion to the brain is the rule.

Despite these presumed mechanisms of infection,

much is unknown about the transmission of the disease.

Relative to the probability of fecal-oral contamination,
simultaneous infestation with both the adult and larval
forms of the parasite is uncommon in those with cysti-
cercosis. Cysticercosis is prevalent in countries where
uncooked pork is eaten, but the disease is also endemic
in India where eating uncooked or raw pork is very
rare (241).

Incidence

This parasitic infestation is relatively common in eco-

nomically developing areas such as Mexico, Central and

South America, Africa, and India. Although it is tradi-

tionally rare in developed countries (242), an increasing

incidence of the infestation in children has been reported
in the United States (243) and in Australia (244), related

to immigrant populations and travelers from endemic
areas. The migration of Mexican and Central American
people into southern and southwestern states in the

United States has made cysticercosis a more common

diagnostic consideration in cities such as Los An-
geles (245).

In Mexico and many Central and South American

countries, 2 to 5 percent of all pigs slaughtered have evi-
dence of cysticercosis. Among all autopsies performed at
the General Hospital in Mexico City, 3.6 percent had

evidence of cysticercosis, while at the Federal University

of Parana, Brazil, 2.2 percent of 7567 brain CT scans
showed evidence of cysticercosis. Cerebral cysticercosis

CNS INFECTIONS / 197

recently accounted for 13 to 33 percent of all space-occu-

pying intracranial lesions at the Mexico City General
Hospital (241). By contrast Courville, from the United

States, found only 22 cases of cysticercosis among 3000

verified brain tumors (246).

Pathology

Pathologically, the disease may result in (1) menin-

goencephalitis; (2) granulomatous meningitis; (3) focal

granulomas (aseptic abscess); (4) focal cysts; (5) hydro-

cephalus (communicating or obstructive); (6) ependymi-

tis; or (7) arteritis (241,247). Living cysts within the brain

incite little or no nearby tissue reaction, and infested
patients may be asymptomatic. When the organisms
within the cysts die (after 18 months or so), they cause an
intense inflammatory reaction around the cyst. Patients
often become symptomatic during this stage, with sei-
zures and focal findings. Finally, dead cysts are reab-

sorbed and calcification of the lesion occurs; heterotopic

bone formation has also been described, presumably sec-
ondary to new bone formation around muscle cysticerci

(248). The parasite also may exist in a racemose form

about the base of the brain. Some evidence suggests that
intraparenchymal brain cysts form if spread to the cen-

tral nervous system occurs via the carotid artery,
whereas the racemose form appears when cerebral
spread has occurred via the vertebral artery.

Clinical Manifestations and Diagnosis

Clinical symptomatology depends upon the number

of cysts, their size, location, and the toxic quality of the
parasite. The clinical course of the disease is character-
ized by remissions and recurrences. Intracranial cysts
produce five basic clinical disorders: (1) convulsions; (2)
"pseudotumors" from diffuse parenchymal involve-

ment with raised intracranial pressure and small ventri-
cles; (3) intracranial space-occupying lesions (cerebral

cysticercosis with focal symptoms); (4) meningoence-

phalitis; and (5) psychiatric disturbances (241). Intraven-
tricular cysts occur in 15 to 20 percent of patients with

neurocysticercosis. Possibly the larval oncospheres reach

the ventricles via the choroid plexus. Intraventricular
cysts may lead to positional headaches, rapid deteriora-
tion of level of consciousness, and death from acute ob-
struction of CSF flow. Obstruction of CSF flow by the

racemose basal form of the disease is usually more

chronic and less catastrophic than obstruction of flow

caused by an intraventricular cyst that happens to block
the intracerebral CSF pathway (249). If the associated

basal leptomeningitis is severe and extends to involve the

cord, amyotrophy and spastic paresis can also occur. Re-

mote cysts about the chiasm may cause blindness (250).

Plain roentgenograms of the skull may reveal evidence

of increased intracranial pressure or intracranial calcifi-

cations. However, CT and MRI scanning are the best
diagnostic modalities. CT scanning is accurate (251) and
is particularly useful in detecting parenchymal calcifica-

tions within dead larvae (252). CT can detect intraparen-

chymatous calcifications and cysts, intraventricular

cysts (with the aid of injected contrast media), and hydro-
cephalus (253). Cysticercosal calcifications, several mil-
limeters in diameter and scattered through the brain par-
enchyma, occur in about 65 percent of patients (254).

Calcifications are more common in adults, whereas dif-

fuse homogeneously enhancing lesions are more often

seen in children (255). Cysts occur about 25 percent of
the time, and these may occur within brain parenchyma
or within the ventricles (254). Over 40 percent will show
hydrocephalus by CT, but scanning may not delineate its
cause because the intraventricular or subarachnoid para-
sitic cysts are of CSF density. Furthermore, racemose
organisms at the base of the brain will not be delineated

by CT scanning. Intraventricular contrast may outline
intraventricular cysts, which may change in position
(255). CT scans of the acute parenchymatous form of
cysticercosis may reveal (1) diffuse low-density areas
within the white matter, which enhance with contrast
plus compressed but undisplaced ventricles: (2) multiple
small low-density areas with discrete rounded central en-
hancement; or (3) large cystic lesions that "ring en-
hance." Multiple cystic lesions occur about 85 percent of

the time, but the lesions are solitary in 15 percent of the

cases (256).

The advent of CT scanning has enabled investigators

to follow the natural evolution of intracranial cysticerco-

sis, and intraparenchymal cysts have been observed to

disappear spontaneously and be replaced by small areas
of calcification (257). Thus, it appears that neural cysti-

cercosis may be well tolerated by some individuals. Spon-
taneous cyst disappearance makes it somewhat difficult
to evaluate drug treatment that also may cause cyst invo-
lution. Contrast enhancement seen about intraventricu-

lar cysts indicates the presence of a granular ependymitis

with adhesions between the cyst wall and ependyma
(255). When this phenomenon is seen, owing to ependy-

mal inflammation, CSF shunting may be necessary even
if the cyst is successfully excised. Before the availability

of CT scanning, Skromme-Kadlubik, Celis, and Ferez

tagged anticyst antibodies to Indium-113. Intracranial
cysticercosal cysts selectively concentrated this isotope

and presented increased activity on radioisotope

scans (258).

MRI scanning, especially with the use of intravenous

contrast material, is also highly accurate in localizing
lesions of cerebral cysticercosis (259). Tl-weighted

198 / CHAPTER 10

images are effective in early detection of intraventricular
lesions (252).

A peripheral blood smear may show eosinophilia. Spi-

nal fluid glucose is usually low, but protein is often ele-

vated; CSF eosinophilia occurs in about 20 percent of
patients. Indirect hemagglutination tests against cysti-

cercosal antigen may be positive in blood or CSF. CSF
complement fixation tests against the parasite generally
yield positive results, but the assay can be difficult to
perform because no standardized antigens or assay tech-

niques exist. Cysticercosal antigens cross-reacting with

echinococcus or schistosomiasis may also be a problem

(260-262). Other tests that have been used to detect cys-
ticercosis include agar gel precipitation, immunoelectro-
phoresis, counter electrophoresis, indirect immunofluo-
rescence, blastoid transformation, and skin reaction,

each with variable rates of success (241).

Treatment

Praziquantel is an antihelminthic that is quite effec-

tive against cysticercosis. Sotelo and associates studied

26 patients treated with this drug (263). After three

months all patients had improved clinically, and 50 per-

cent were asymptomatic. The drug is tolerated quite

well (264).

Patients receiving praziquantel exhibit side effects ow-

ing to the brain's inflammatory reaction to dying and

dead parasites. To combat this reaction, some authors
have recommended concomitant steroid administra-

tion. Ciferri compiled four large series of patients with

neurocysticercosis treated with praziquantel (265). Only

11 to 16 percent of patients who received steroids along

with praziquantel exhibited adverse reactions, whereas
92 to 100 percent of patients receiving praziquantel

alone had adverse reactions from dying parasites. De-

Ghetaldi, Norman, and Douville concluded that prazi-

quantel alone is a remarkably safe drug when adminis-
tered to healthy volunteers but that it becomes
increasingly hazardous in patients with severe neurocys-
ticercosis (266). These investigators believed that ste-

roids should be given along with praziquantel; the bene-
fits of administering steroids for one to two months to
suppress the brain's reaction to dying and dead organ-
isms far outweighed the risks of potential, steroid-in-
duced side effects.

The efficacy of praziquantel may radically alter the

indications for surgery in neurocysticercosis. In the past,
it was pointed out that up to 90 percent of patients with
CT-demonstrated hemisphere lesions had a nonprogres-
sive course not requiring surgery (267) and that patients
presenting with epilepsy as the only clinical manifesta-

tion were often successfully treated with standard anti-

epileptic drugs alone (241). One may surmise that pa-
tients presenting with a "pseudotumor" syndrome from

miliary cysts, edema, and small ventricles can be success-

fully treated with praziquantel and steroids.

Should surgery become necessary, the best operative

results (75 percent improvement, 24 percent mortality)
have been obtained with excision of cysticerci, which
form a single, discrete, space-occupying lesion within the
brain and produce focal signs. The poorest results (28
percent improvement, 67 percent mortality) have been
seen in patients who developed basal leptomeningeal in-
fection (268). Some authors recommend surgical exci-
sion of cysticercosis cysts when they produce focal symp-
toms and are surgically accessible (269). In a series of 141
patients with neurocysticercosis, over 50 percent were
cured following praziquantel treatment; intraventricular

cysts were unaffected by the drug and had to be surgi-

cally removed (270). Intraoperative ultrasound (neuro-
sonography) is helpful in detecting subcortical lesions
(271). Many who are experienced with cysticercosis cere-
bri advocate leaving basal cysts in situ. They prefer to

deal with the problem of CSF obstruction by communi-

cating the temporal horn with the cisterna ambiens or
using a standard CSF shunt. Spread of the organisms by
shunting the CSF is unlikely because cysticercosis cysts

are rarely found in the lateral ventricles. Intraventricular

cysts are potentially dangerous because they may mi-
grate, plug CSF circulation pathways within the brain,
and lead to acute hydrocephalus and abrupt death. They
may be removed stereotaxically or by a direct surgical
approach (245). If the cyst is unruptured or has not in-
cited a granular ependymal reaction (determined by en-
hancement of the cyst on preoperative CT scans), simple

cyst removal may suffice. Sometimes, CSF shunts are
required even after successful cyst removal if tissue reac-
tion to the parasite obliterates CSF pathways (245,267).
Occasionally, patients with acute obstructive hydroceph-
alus will require shunting before cyst removal in order to
reduce intracranial pressure (249).

Echinococcosis Granulosus

Life Cycle and Incidence

Hydatid disease in humans is caused by the larval

stage of the tapeworm Echinococcus granulosus. The
mature worm lives in the intestine of the dog. Ova passed

in dogs' feces infect grass eaten by sheep, in whose lungs,
liver, or other abdominal organs the ova develop into
encysted embryos. If dogs eat the offal of infected sheep,
the parasite matures in the dogs' intestine and its life
cycle is repeated. Human infection arises by contamina-
tion of food by dust containing viable ova or by oral

contamination from the hands after handling infected
dogs. Only about 2 percent of those who develop echino-

coccal disease have central nervous system involvement
(272). Nevertheless, hydatid cysts account for about 2 to

CNS INFECTIONS

199

3 percent of intracranial space-occupying lesions in An-
kara, Turkey (273). Children are affected 2.5 times more

frequently than adults. In countries where hydatidosis is
common, up to 50% of childhood tumors of the CNS
turned out to be hydatid cysts.

Pathology

The disease exists in two forms. Intracranially, the dis-

crete and encapsulated hydatid cyst acts as a space-occu-
pying lesion. Because cerebral hydatid cysts are fre-

quently single, surgical therapy is often successful. Most

cysts start in the subcortical area and spread deeper into
the white matter. The cerebral hemispheres are more of-
ten infected than the cerebellum. Intraventricular and
even intrasellar cysts have been reported (274,275). The
unencapsulated parasite may invade the bone of the cra-
nium.

Clinical Manifestations and Diagnosis

In children, the peak incidence occurs between ages 5

and 10. Affected children may have raised intracranial
pressure, diminished visual acuity, mental changes, ho-
monymous field cuts, and hemiparesis. Characteristi-
cally, however, one is confronted with a child in good
general health who lives in an endemic rural area and has
elevated intracranial pressure without focal findings
(276). In the adult, the clinical picture is less well de-
fined. Increased intracranial pressure is usually evident,

but the differentiation between echinococcal cysts and
tumors may be difficult.

Plain x-rays of the skull in the child may show suture

separation or thinning of the cranial vault, whereas RN

scans reveal absence of uptake at the cyst site. If angiogra-

phy is done, it may reveal significant vascular displace-
ment by an avascular mass. CT scanning reveals a cyst,

often with nonspecific mass effect (277). Calcification of

the cyst wall may occur, and its presence raises suspicion
of echinococcosis cyst. Rarely, there is a fine enhancing
rim. The cyst may occur in various sites, including the

aqueduct of Sylvius (278) and the skull.

Treatment

In the presence of increased intracranial pressure, the

cyst fluid may be aspirated by puncture via a burr hole
and may be followed by systemic antihelminthic treat-
ment with mebendazole (279) or albendazole (280). Sur-
gical excision of the encapsulated cyst may be necessary

(Fig. 3). The removal can be done by cortical incision,
exposure of the cyst, and gentle irrigation between cyst

wall and brain. Ozgen and colleagues reported 11 succes-
sive cures with surgery (281).

FIG. 3. Hydatid cysts removed at surgery, unruptured. The

outer laminated membrane has been opened, revealing so-
called brood capsules contained within. (Courtesy of Dr.
George Craven, Department of Neurosurgery, Louisiana
State University Medical Center.)

Cranial hydatid disease also represents an unencapsu-

lated form of the parasite that occurs in either the cranial
base or vault. It may result in increased intracranial pres-
sure, focal neurological disturbances, skull deformity,

and cranial nerve palsies. Involved bone of the vault may
be widely resected, but this may not be possible with a

basal lesion.

Schistosomiasis

Infestation by the trematode worm Schistosoma af-

fects an estimated 200 million people worldwide (282).
Acute cerebral schistosomiasis can cause a fulminating

encephalitis, whereas the chronic form of the disease
produces intracranial granulomas with obstruction to ce-

rebrospinal fluid flow, elevated intracranial pressure.
and localizing signs. Unfortunately, there are no specific

clinical features that are pathognomonic of the disease.

Schistosomicidal chemotherapy supplemented with cor-
ticosteriods is usually effective (283).

Toxoplasmosis

Toxoplasmosis gondii. an obligate intracellular proto-

zoan, causes one of the commonest infections in Amer-

ica; from 20 to 70 percent of adults in the United States

demonstrate Toxoplasma antibodies. In immunocom-
promised individuals, protozoa invade and destroy cells

200 / CHAPTER 10

producing necrotic regions surrounded by an intense

mononuclear reaction. Patients may become immuno-

compromised secondary to AIDS, secondary to treat-
ment for malignancies, or following organ transplanta-
tion (284-287). In the CNS, T. gondii infections can be
classified into one of three patterns: (1) diffuse encepha-
lopathy with or without seizures; (2) meningoencephali-
tis; or (3) single or multiple progressive mass lesions. The

T. gondii trophozoites may be identified by Giemsa-

stained preparations of abscess aspirate. Inoculations of
purulent material into mice and fluorescent antibody
techniques also may lead to definite identification of
Toxoplasma organisms. Pyrimethamine and sulfadia-
zine (or triple sulfonamides) are the current drugs of
choice, and prompt initiation of therapy provides a more
favorable outcome. Naturally, ultimate prognosis de-
pends on the severity of brain involvement plus the
seriousness of the underlying disease. If one is dealing
with an immunocompromised patient and the CT scan
suggests toxoplasmosis, empirical medical treatment
may begin and the patient is followed by serial CT scans.
If the lesions clear, this presumes T. gondii infection, and

brain biopsy may be avoided.

the spinal epidural space directly from the lungs, because

an extradural thoracic location is most common.

Although medical therapy with praziquantel provides

primary treatment, surgery may be performed for intra-
cranial mass lesions that cause increased intracranial
pressure. Small cysts may be entirely enucleated. The
contents of large cysts are evacuated, but the walls are
left behind.

Entamoeba Hlstolytica

Brain abscesses caused by Entamoeba histolytica

(292-295) usually have a hematogenous origin from E.
histolytica abscesses of the lung or liver, although at least
five cases of direct spread of this organism from bowel to
brain have been reported. From 0.7 to 8 percent of he-
patic amebiasis will have associated brain involvement.

E. histolytica brain abscesses are usually solitary and un-

encapsulated. The abscess progresses rapidly and fre-
quently ends fatally, but several instances have been re-

corded of survival following aspiration and antiamebic

drug therapy.

Paragonimiasis (288)

Paragonimiasis is a parasitic infection caused by the

lung fluke Paragonimus westermani and related species.
The infection is prevalent in the Far East, Southeast
Asia, some parts of Africa, and South America. In one

endemic area, 24 percent of space-occupying lesions

within the brain were caused by Paragonimus. It is
caused by the ingestion of inadequately cooked crusta-
ceae contaminated with the larval form Paragonimus,

which migrate from the duodenum to the lungs. Most

investigators believe that immature or mature worms
follow vascular structures from the chest to the head and
enter the brain via foramina at the base of the skull.
Entrance through the jugular foramen is highly suspect
because most cerebral lesions are posterior, particularly
in the occipital, parietal, and temporal lobes. Cerebral
paragonimiasis may present as an acute meningoence-
phalitis, a well-encapsulated granuloma, or a chronic
calcified lesion. Seizures, headache, visual disturbances,
and hemiparesis are the most common symptoms and
signs. Plain x-rays of the skull may reveal posterior calci-
fications. CT scanning reveals ring-like or nodular en-
hancing masses in the early stages (289,290). Shell-like
calcified clusters occur in the chronic form (291). Cere-

brospinal fluid may be normal or abnormal. Occasion-
ally, Paragonimus ova may be seen in the CSF. Comple-
ment-fixation tests of cerebrospinal fluid against
Paragonimus antigen are positive in 40 to 80 percent of
cases of cerebral infestation. The parasite may also in-

volve the spinal cord. The worms probably migrate into

Trypanosomiasis

A studyTias suggested that subcurative treatment of

systemic trypanosomiasis may permit the parasite to
enter the brain and to cause meningoencephalitis (296).
Poisson and associates reported the occurrence of pseu-
dotumors associated with Trypanosoma gambiense
(297). Clinical signs included progressive hemiplegia and
papilledema, although the hemiplegic form has been re-

ported as unusual (298). CT scans demonstrated asym-
metrical hypodense areas in the white matter, and arteri-

ography showed vascular displacement. Serial CT
scanning revealed associated cerebral edema and demye-
lination. Arsenicals plus corticosteroid treatment led to a

rapid clinical improvement in their patient. The differ-

ential diagnosis includes tuberculosis, syphilis, and fun-
gal infection (298).

Fungal Brain Abscess

Fungal infections of the central nervous system occur

sporadically among normal persons. More commonly,
however, such infections are found in debilitated, dia-

betic, or immunocompromised individuals. Recipients
of organ transplants, patients with lymphomas, acute
leukemia or aplastic anemia, and those on cytotoxic che-
motherapy are also susceptible, as are those with abnor-

mal immunoglobulins (299,300). Because of the altered
immune response, the host is often unable to confine a

fungal brain abscess, and CT scans in such cases often
show poorly circumscribed, low-density lesions with lit-

CNS INFECTIONS

201

tie contrast enhancement. These CT characteristics in

patients with fungal brain abscesses are often associated

with a poor prognosis (301). Mortality following fungal
brain infection is high, not only because of the brain
infection itself, but also because of the underlying dis-
ease.

In one neurosurgical series of 78 patients with fungal

infections of the CNS, Coccidioides immitis and Crypto-
coccus neoformans accounted for two-thirds of the in-
fections; 15 percent were associated with intracranial
mass (302).

Coccidioidotnycosis (303,304)

Coccidioidomycosis is caused by a fungus that exists

in the mycelial form in hot desert soils and occurs as
spherules in the human host. Brain infection usually oc-
curs as a meningitis that is generally fatal. Hydrocepha-
lus and increased intracranial pressure occur because of
obstruction to CSF flow. Shunts are usually required for
control of CSF. Until recently, amphotericin B was the

only effective treatment, and it was given either by re-
peated lumbar injections or via a bubble reservoir placed
under the scalp and connected to a lateral ventricle by a
silicone tube (Ommaya reservoir). Amphotericin B is

toxic in itself, and its administration has resulted in sig-

nificant morbidity. The imidazole antifungal agents, mi-

conidazole and ketoconazole, may be effective with less

morbidity than amphotericin B. Miconidazole is given

intraventricularly with an Ommaya reservoir, and keta-
conazole is taken orally.

Cryptococcosis (305,306)

CNS cryptococcal infection occurs in persons exposed

to pigeon and chicken droppings and appears particu-
larly in debilitated, immunocompromised patients. The

organism Cryptococcus neoformans reaches the brain or

spinal cord by way of the blood and usually produces a
meningitis, although space-occupying lesions that re-

quire excision have been reported. Currently, 60 percent
of cryptococcosis patients who receive amphotericin B
are cured. Addition of 5-fluorocytosine may be useful,
but this is not well established.

Aspergillosis (301,307-315)

Aspergillosis is caused by a fungus of the genus Asper-

gillus. The infection can involve the meninges, paren-
chyma, or blood vessels. A. fumigatus is the most com-
mon species causing disease in man. Usually the
organism enters the CNS by hematogenous spread from
lung or intestine, but occasionally direct penetration oc-
curs from an involved sinus or orbit. Although CNS

aspergillosis can occur in otherwise healthy persons, the

disease is often associated with drug addiction. AIDS.
diabetes mellitus, carcinomatosis, immunosuppression.
and other debilitating disorders. Generalized aspergillo-

sis spreads to the CNS about 1 8 to 50 percent of the time,
In the CNS, lesions can be either acute
purulent) or chronic (granulomatous). Fungal aneritis
may be caused by extension of the fungus into the nails
of cerebral arteries, and this may result in cerebral infarc-

tion or hemorrhage. In one series of nine fungal brain
abscesses among immunocompromised persons, eight
were caused by aspergillosis. The clinical findings de-
pend upon the site and extent of the lesion. CT scans

:

delineate the extent of neuraxis involvement but are not
specific for aspergillosis. Spinal aspergillosis has been re-
ported in normal individuals, in the immunocom-
promised, and in patients who have had lumbar disc
surgery. Although intraventricular and systemic ampho-
tericin B (perhaps in combination with rifampin) can be
effective in some cases, the ultimate prognosis is usually

guarded because of the underlying systemic disease.

North American Blastomycosis (3 16-322)

Blastomycosis is a fungal disease caused by Blasto-

myces dermatitidis. a soil saprophyte common in the

central part of the United States. The portal of entry into
the body is the lung. Pulmonary blastomycolic lesions

may be confused with tuberculosis. Meningitis is the
most common form of CNS blastomycosis, but solitary

mass lesions in the brain occasionally occur. Clinically.
patients may present with headache, coma, confusion.
memory loss, aphasia, paresis, increased intracranial
pressure, or signs of meningitis. Diagnosis is difficult un-
less blastomycosis is present elsewhere. Skin testing has
limited value, because the blastomycosis antigen cross-
reacts with Histoplasma and Coccidioides. White blood
cell count and erythrocyte sedimentation rates are gener-

ally normal. CT scanning reveals an isodense or slightly
hyperdense solitary mass with contrast enhancement
and surrounding edema. The scan appearance may be
suspicious for tumor. Definitive diagnosis is based on
biopsy, culture, or/both. Amphotericin B may be cura-
tive, but surgicalremoVal of the intracranial lesion may

be r e q u i r e d .

Phycomycosis (Mucormycosis) (323-326)

Cerebral mucormycosis is an acute, rarely curable

fungal disease that affects the nasal sinuses, orbit, and

brain. The fungus usually becomes pathogenic for hu-
mans, in association with predisposing debilitating con-
ditions, such as diabetic acidosis, and altered immune
conditions, including use of antibiotics or corticoste-
roids. Cerebral mucormycosis, however, has been re-

202 / CHAPTER 10

ported following open brain injury alone. Patients with

mucormycosis often have proptosis, orbital cellulitis,

and total ophthalmoplegia. Central nervous system in-

vasion (acute meningoenccphalitis and purulent menin-

gitis) occurs along arteries that transverse the lamina cri-
brosa. The fungus has a predilection for arterial
invasion, which can lead to thrombosis and cerebral in-
farction, hemorrhage, or dissecting aneurysms.

Paranasal sinus involvement appears as mucosal

thickening on CT scans. Bone destruction is occasionally
seen. CT scan evidence of intracranial involvement is
shown by presence of abscess or infarction. The fungal
abscess appears as a low-density mass with variable pe-

ripheral enhancement and little surrounding vasogenic

edema.

Treatment includes control of the underlying cause,

local drainage, or debridement of the involved tissue and

use of amphotericin B. both systemically and via local
irrigation. Hyperbaric oxygen has been used for treat-

ment of the disease by providing increased oxygen perfu-

sion of tissues distal to occluded arteries. Hyperbaric ox-

ygen may reduce local acidosis and thereby inhibit the

growth rate of fungus.

Histoplasmosis (327)

Histoplasmosis is caused by the dimorphic fungus,

Histoplasma capsulalum, which rarely infects the cen-

tral nervous system. When the CNS is infected, meningi-
tis usually results, but occasionally parenchymal granu-
lomas occur. Amphotericin B is used for treatment.

Candidiasis (328-330)

Candidiasis is usually a chronic infection caused by

various species of the imperfect fungus, Candida. Cen-

tral nervous system infection usually follows systemic

disease in debilitated persons with diabetes, malignan-

cies, or immunologic problems in those treated with anti-

biotics, steroids, or immunosuppressive drugs. The usual

infection is meningitis, but parenchymal involvement

may occur. In infants, Candida brain abscess may occur
in association with gastrointestinal lesions, postopera-

tively, or following treatment with antibiotics. Candida
discitis following bowel surgery in an adult has been re-
ported. Amphotericin B and 5-fluorocytosine are effec-
tive drugs, but the ultimate prognosis is often poor be-
cause of the underlying disease.

Neurological Sequelae of Amphotericin (331)

Intrathecal administration of amphotericin B may

cause transient or permanent spinal cord dysfunction
(myelopathy). Pathological studies following amphoteri-

cin myelopathy in one patient disclosed no evidence of

arachnoiditis, suggesting that the dysfunction results

from a vascular abnormality (i.e., possible transient
spasm).

If a patient receiving amphotericin B experiences tran-

sient spinal cord symptoms, the amount of drug given
intrathecally may be reduced and the injections sched-
uled farther apart. Alternatively, the drug may be given
intraventricularly by means of a reservoir unit. Consider-
ation may be given to changing medication, but when
amphotericin B is essential, this may prove difficult. Mi-
conazole may become an alternative to amphotericin B.

Acquired Immunodeficiency Syndrome (AIDS)

Acquired immunodeficiency syndrome (AIDS) and

AIDS-related complex (ARC) have been shown to be
caused by the human immunodeficiency virus, HIV. As
a result of the immune deficiency, the body is subject to a
wide spectrum of opportunistic infections and malig-
nant tumors. In addition, there is increasing evidence
that the human immunodeficiency virus type 1 (HIV-1)

is neurotropic and that it can invade the brain directly,

although its pathogenesis is not well understood
(332,333).

Because the mortality of AIDS is 100 percent, a large

literature concerning its protean pathological manifesta-
tions has emerged. The nervous system is significantly
involved in the majority (at least 74 percent) of cases
(334-336). A predominant feature is opportunistic in-
fections (cryptococcal infection, toxoplasmosis, cytomeg-
alovirus, histoplasmamicroabscess). Fungal infection, es-
pecially by cryptococcus, is the most common cause of

meningitis (337), and toxoplasmosis, a protozoan infec-

tion, is the most common cause of abscess formation

(337). Simultaneous infection by more than one microor-
ganism occurs occasionally. Bacterial infections of the
CNS are uncommon, but HIV encephalitis is common

(335). Primary Cl>fS lymphoma or lymphoma meta-

static from extracfanial sites occurs in a variable propor-
tion of the cases (336^338). There are cases in which in-
fection and^umor odcur in the same patients (339).
Spinal cord involvement occurs with demyelination in

the lon£ tracts of posterior columns (340).

Between 50 and 60 percent of patients with AIDS may

be expected to develop a neurological complication

(341). Approximately 10 percent of patients develop in-

tracranial mass lesions, and, in about 25 percent of these
patients, the lesion is identified before the diagnosis of
AIDS is established (342). The two most common mass
lesions are toxoplasmosis abscess and lymphoma. These
lesions have neurosurgical implications in terms of the

question of biopsy versus medical management.

A large proportion of both the AIDS and non-AIDS

population is seropositive for toxoplasmosis, indicating

CNS INFECTIONS . 3

previous subclinical infection. In patients with AIDS, in-
fection with the protozoan, Toxoplasma gondii, appears
to result from reactivation of a prior latent infection
(343). The clinical manifestations of CNS involvement,
especially focal seizures, suggest a focal process. There
may or may not be a focal neurological abnormality.
Lumbar puncture is not helpful, because the CSF may
show only a nonspecific lymphocytic pleocytosis. Exami-
nation of the CSF, however, is useful in excluding menin-

gitis caused by other organisms, including Cryptococcus

neoformans (343). On the other hand, clinical judgment
needs to dictate whether the risk of the lumbar puncture
producing cerebral herniation in the presence of a space-
occupying intracranial mass lesion is worth the informa-

tion concerning the question of meningitis. Measure-

ment of CSF antibody to T. gondii is not diagnostically
helpful (343). AIDS patients with toxoplasmosis gener-
ally have evidence of past infection (IgG antibody); there-
fore, although serologic testing has limited value for the

diagnosis of toxoplasmosis in AIDS patients, absence of
the IgG antibody to T. gondii tends to exclude that diag-
nosis (344).

Both CT and MRI scanning are useful in demonstrat-

ing toxoplasmosis in the brain. The lesions may be soli-
tary, but they are usually multiple. The basal ganglia are
the most common site, but the lesions may occur in any
portion of the brain including the cerebral cortex, cere-
bellum, and brainstem (345,346). There is considerable
surrounding edema. For CT scanning, double-dose con-
trast increases the sensitivity of the imaging; ring en-
hancement is common (Fig. 4). MRI may be slightly
more sensitive than CT scanning, but it is not more diag-
nostically specific (346). RN brain scintigraphy (isotope

brain scan) may also demonstrate localized intracranial
infection (347), although resolution is inferior to that of
CT or MRI scanning.

If the diagnostic studies do not reveal a clear-cut diag-

nosis of toxoplasmosis, the question of carrying out a
biopsy for definitive diagnosis arises. This can be carried
out with reasonable safety by CT-guided biopsy tech-
nique (under local anesthesia) or by open craniotomy
with the aid of ultrasound imaging for localization of the

lesion (343). Another option is that of placing the patient
on a trial of the drug combination of pyrimethamine and
sulfadiazine. This regimen is highly effective, with clini-
cal improvement and shrinkage of the lesions on CT

scan usually apparent within one to two weeks. Treat-
ment must be continued indefinitely. If there is no im-

provement within two weeks, biopsy may then be consid-
ered (342,343).

In patients with AIDS, primary CNS lymphomas oc-

cur in about 2 percent of cases, and in about one-third,
the tumor is the first manifestation of AIDS (342). The
patients may present with confusion, headaches, visual
disturbance, memory impairment, and focal neurologi-
cal abnormalities such as hemiparesis (342,348). Sci-

FIG. 4. CT scan with IV cor lancement, showing ring

enhancement of a lesion in tr.e region of thalamus/basal gan-
glia (arrow). The patient was a 38-year-old woman from Haiti
who presented with focal seizures, a rapidly progressive he-
miparesis. and a dedning level of consciousness; she was
found to be HlV-positive, CT-guided siereotaxic biopsy re-

vealed a toxoplasmosis abscess. She was then treated with

pyrimethamine and sulfadiazine, with temporary improve-
ment in her neurological status, but she subsequently deter-
iorated and died.

zures occur in about one-third of the patients. CT or
MRI scanning reveals mass lesions that are multiple in
about two-thirds of the cases; the lesions are usually con-
trast-enhancing on CT scanning. MRI is reported as be-
ing more sensitive than CT and may show more areas of
involvement, but it is not more specific in differentiating
the lesion from other AIDS-related diagnostic possibili-
ties (349).

Other AIDS-related diagnostic possibilities in patients

with focal lesions are cerebral toxoplasmosis, progressive
multifocal leukoencephalopathy, fungal or bacterial in-
fection, and hemorrhage (350).

Lumbar puncture for CSF examination may show

slight increase in protein and mild lympocytic pleocyto-

sis (348). CSF cytology generally does not reveal abnor-

mal cells. Because the CSF findings are nonspecific, the
main value of lumbar puncture in diagnosis of CNS lym-

phoma is the ruling out of meningitis such as cryptococ-
cus. As mentioned previously, the risk of cerebral her-
niation has to be considered in judging whether to carry
out lumbar puncture where the CT or MRI scan shows

significant intracranial mass, especially if the scan shows

a hemispheral shift.

For definitive diagnosis, a CT-guided stereotaxic

biopsy may be performed. However, because toxo-

204 / CHAPTER 10

plasma abscesses are the most common type of cerebral

mass lesion in patients with AIDS and the most amena-

ble to treatment, Rosenblum, Levy, and Bredesen recom-
mend a three-week antibiotic trial with pyrimethamine
and sulfadiazine for any patient with AIDS and intracra-
nial masses (342). Steroids may also be given briefly if it
is necessary to control cerebral edema. Clinical improve-
ment and shrinkage of the lesions confirm toxoplasmo-
sis as a diagnosis. However, if the patient is not likely to
survive the three-week antibiotic trial or if any of the
masses fail to respond to the antibiotic treatment, then
biopsy is recommended. Furthermore, because toxo-
plasmosis lesions are usually multiple, a biopsy should
probably be performed for solitary mass lesions.

Radiation therapy is the recommended treatment for

CNS lymphoma, possibly in conjunction with chemo-
therapy and steroids (351). Although the neoplasm re-
sponds favorably to radiation therapy, patients usually
die of other AIDS complications.

Osteomyelitis of the Skull

The skull is relatively resistant to infection, and the

occurrence of infection is usually associated with one of

the following:

1. Infection of an adjacent air sinus, usually the frontal

sinus;

2. Head trauma with scalp laceration, particularly when

associated with skull fracture; or

3. Postoperative infection, following a craniotomy.

One series reported a 5 percent postoperative infection
rate following craniotomy (352), and another series re-
ported a 7 percent incidence of craniotomy infections
(353). In the latter series, bone flap infections repre-
sented more than half of all infections after supratentor-
ial craniotomy. and bacterial meningitis accounted for
more than half of the infections following suboccipital

craniotomy and translabyrinthine operations.

Cranial osteomyelitis may be a low-grade infection

limited to the skull, or it may be associated with epidural
or subdural empyema. with life-threatening potential. In
acute osteomyelitis of the skull, the patient may have
fever and localized pain, tenderness, and swelling in the

area of the involved bone. On plain x-rays, localized
bone destruction may not become evident until two

weeks after the onset of the osteomyelitis (Fig. 5). Al-
though the area of infected bone may be identified on
plain skull films, additional studies, including isotope
bone scan and CT-scan of the skull, may be needed to
clarify the diagnosis. The offending organism is usually

Staphylococcus, either S. aureus or S. epidermidis, or
mixed flora (354).

In acute osteomyelitis, antibiotics are the main treat-

ment. In both the acute and chronic forms, it is impor-

FIG. 5. Plain skull film showing area of chronic osteomyelitis

in the frontal bone (arrows) in a patient who had sustained a

depressed skull fracture and frontal paranasal sinus injury.

(Courtesy of Dr. George Craven, Department of Neurosur-
gery, Louisiana State University Medical Center.)

tant to obtain a culture of the infected area either by

needle aspiration or by open operation. Treatment of an
infected contiguous source, such as frontal sinusitis, is
also necessary. It has been recommended that antibiotics

be given intravenously for one to two weeks, then given

orally for 6 to 12 weeks. Intermittent antibiotic serum

levels should be obtained while the patient is on oral

therapy (355). Alternatively, some authors prefer a bi-

weekly course of intravenous antibiotics, with no need

for continuation with oral drugs (A. Molavi, Hahne-

mann University, personal communication). Despite the

use of antibiotics, chronic osteomyelitis is best treated
also with surgical resection (craniectomy) of the in-
volved bone (354).

SPINAL ABSCESS

Pyogenic Infections

Vertebral Osteomyelitis

Pyogenic vertebral osteomyelitis is commonly asso-

ciated with antecedent bacterial infection elsewhere in
the body. Bacteria from the primary site, such as pelvic
or urinary tract infection, spread hematogenously to the
vertebral column, either via arteries or via the veins of

Batson's plexus (356-358). A septic embolus produces a

localized bone infarction, which results in the develop-

ment of osteomyelitis (359). The richly vascularized ver-
tebral body end plate region is the commonest site of

initial infection from hematogenous spread. This dis-
order occasionally follows penetrating trauma or spinal

CNS INFECTIONS / 205

surgery. Staphylococcus aureus is the most common or-
ganism responsible for vertebral osteomyelitis, but

gram-negative organisms have also been implicated

357,360-362). Pseudomonas aeruginosa is commonly

isolated from vertebral osteomyelitis in heroin ad-

dicts (363). I

In children, spinal infection usually has an abrupt on-

set, with malaise, fever, back pain, and spinal tenderness.
In adults, however, symptom onset is usually gradual,
and up to three months may be required to make the
diagnosis (364,365). In both adults and children, diagno-
sis is commonly delayed, owing to the nonspecificity of

the symptoms. For example, spinal pain secondary to
vertebral osteomyelitis may be the primary manifesta-

tion of infection elsewhere, such as endocarditis

( 366,367). Osteomyelitis should be included in the dif-

ferential diagnosis of persistent or worsening backache
in elderly patients with degenerative spinal osteoarthritis

(368). In patients undergoing long-term hemodialysis,

however, plain x-ray changes in the spine suggest osteo-

myelitis but, on investigation, turn out to be "pseudoin-
fection." The cause of these changes is not known (369).

The absence of a prevertebral soft-tissue mass on MRI
scanning in hemodialysis patients suggests that the spi-
nal radiographic changes are not due to infection (370).

Osteomyelitis is similarly considered in patients with os-

teoporosis and vertebral body collapse who have back
pain, fever, and elevated sedimentation rate (371). Cer-
vical osteomyelitis is considered a diagnostic possibility

after anterior spine surgery (372). penetrating wounds of
the neck (373), panfacial trauma (374), or tracheo-
esophageal puncture for voice rehabilitation (375).

There is little or no fever, and adults usually have n/o

malaise. Back pain is present in about two-thirds of the
cases, particularly if the mobile cervical and lumbar ar-

eas are affected rather than the fixed, thoracic spine.

Usually, on palpation, point tenderness is evident at the
involved site. In adults, the leukocyte count is seldom

raised, but the erthrocyte sedimentation rate (ESR) is

usually elevated. Some authors have noted an associa-

tion of vertebral osteomyelitis with diabetes (157,376),

but others have not (361). A raised sedimentation rate is

said to be the best clue that backache in a diabetic patient
is due to something other than benign osteoarthritic
changes (376).

Thoracic and lumbar vertebrae are most frequently

involved; the vertebral bodies are more commonly af-
fected than the posterior elements. Generally, more than

one spinal level is affected. Pus from an infected vertebra
may form a paravertebral abscess or, more importantly,

an epidural collection that may compress adjacent

neural structures. Collapse of a vertebral body may result

in gibbus formation that may impinge on the spinal cord
or cauda equina. Either of these mechanisms may lead to

paralysis. In one series, 3 of 28 patients with vertebral
body infection subsequently developed paralysis (361).

Plain x-ray findings lag behind signs and symptoms by

two to eight weeks (126). These findings consist of bone
rarefication, loss of bony trabeculation close to the carti-
laginous plate, and narrowing of the vertebral disc space
between involved adjacent vertebrae. An important x-
ray observation differentiating osteomyelitis from
cancer metastasis is the finding that the intervertebral
disc is commonly destroyed by osteomyelitis, whereas it
is generally preserved in metastatic disease (377). There
are exceptions to this rule, however, so intact vertebral
endplates on MRI scanning do not necessarily exclude
osteomyelitis in favor of metastatic disease (378). Verte-
bral body collapse is common. In chronic infections,

there may be rapid bone regeneration with the develop-

ment of dense new bone. RN scanning is sensitive in

diagnosing infection in the jirst several weeks of verte-
bral osteomyelitis. The combination of an abnormal Tc-
99m bone scan^ana an abnormal Ga-67 scan, showing
focal uptake in the spine, are reasonably specific for diag-

nosis of vertebral osteomyelitis (379). On the other hand,

the finding of In-111 labeled leukocytes (In-111 WBC) is
less specific (380). CT scanning may show bony abnor-
malities before plain x-rays do (381), and it has the ad-

vantage over RN scanning of distinguishing bony from
disc space involvement. CT scanning after intravenous
contrast injection enhances the rim around an epidural
abscess, which adds to the usefulness of this modality
(382). MRI scanning has the same accuracy and sensitiv-
ity as radionuclide scanning in detecting osteomyelitis
(377). MRI scans show obliteration of the margin be-

tween the disc and the vertebral end plates (383) (Fig. 6).
RN scanning is less subject to motion degradation than
MRI scanning. If patients cannot tolerate MRI scanning
because of claustrophobia, RN scanning can be per-
formed (377). Myelography with water-soluble contrast
followed by CT scanning is useful in outlining epidural
abscess, but the value of myelography is declining be-
cause of the availability of RN, CT, and MRI scanning.

The responsible organism may be identified by blood

culture in cases of acute vertebral osteomyelitis, but is

usually negative in chronic osteomyelitis (384). If blood
cultures are negative, it is recommended that the respon-
sible organism and its susceptibility to antibiotics be
identified. This can be accomplished by percutaneous
needle aspiration under fluoroscopic or CT guidance or
by open biopsy. Percutaneous CT guidance has been re-
ported as safe, accurate, and superior to fluoroscopic
guidance (384-387). Both aerobic and anaerobic culture
should be carried out, as well as culture for tuberculosis,
fungi, and search for parasites.

Treatment of vertebral osteomyelitis without neuro-

logical deficit consists of bed rest and immobilization,

along with antibiotic therapy based on meticulous sus-

ceptibility testing of the offending organism(s) (2). Paren-
teral antibiotics are given for six to eight weeks, and oral
therapy should continue for an additional eight weeks

206 / CHAPTER 10

FIG. 6. MRI scan in 37-year-old patient with a history of drug
addiction presenting with thoracic spinal pain and rapidly pro-
gressive paraparesis. The MRI scan suggests osteomyelitis,
showing vertebral body collapse, destruction of the end-
plates, and spinal cord compression. The involved vertebral
bodies and intervening disc were resected by a thoracotomy
approach, and a strut bone graft was placed at the site of the
vertebral corpectomies. The patient had an excellent recov-
ery of neurological function. The organism proved to be

Staphylococcus, for which she was placed on an antibiotic

regimen.

(388). External immobilization may prove a useful ad-

junct to prevent bony collapse and may increase patient

comfort. Significant paravertebral abscesses may require
drainage. A metal stabilization rod may be implanted at

the time of surgical drainage to control pain and to per-
mit postoperative mobilization (389). Should the spinal
cord be compressed by epidural pus or gibbus, decom-
pression of the spinal cord will be necessary either by
laminectomy or by an anterior or lateral approach. How-
ever, patients with spinal epidural abscess who are in
poor medical condition or are without neurological defi-
cit may be treated with antibiotics alone without sur-
gery (388).

Owe Space Infection

Pathophysiology

Infection of the disc space is a relatively uncommon

complication following open (390) or percutaneous
(391) excision of a herniated disc (usually in the lumbar

area) (390) or after lumbar chemonucleolysis (392).
Somewhat more common is the spontaneous develop-

ment of disc space infection without prior spinal surgery.

The latter form is thought to be produced by the hema-
togenous spread from an infective source elsewhere in
the body, although a specific source often remains unde-
termined. The spontaneous form of disc space infection
tends to be more common in children than in adults,
which has been attributed to the observation that the disc
space early in life is well supplied with blood vessels from

the adjacent vertebrae and that these vascular channels
gradually disappear by the second or third decade. The

normal adult disc is relatively avascular, which probably
accounts for the lower frequency of blood-borne infec-

tion of the disc in adulthood.

Staphylococcus aureus is nearly always the offending

organism in children. This bacterium also predominates
in adults, but a wide variety of other organisms may be
implicated, and hence it is important to isolate the organ-

ism, especially in adults, before making a decision re-
garding selection of antibiotic therapy.

Clinical Manifestations

Discitis can affect the intervertebral disc at any level of

the spine but is most common in the lumbar region.
Children may be affected from approximately one year
of age through adolescence. There is a higher incidence
of discitis in diabetic adolescents. Children commonly
present with low-grade fever, irritability, and malaise. If
they are able to describe symptoms, back pain is a promi-
nent complaint, and paravertebral muscle spasm is a sig-
nificant finding on examination. Sometimes the child

will present with a limp or will refuse to walk, and the
spinal origin of the problem may be missed unless the

examiner palpates the spine in search of point tenderness

and muscle spasm.

In adults with spontaneous discitis, the onset is gener-

ally more insidious, extending over weeks to months be-

fore the diagnosis is suspected. Patients complain of
well-localized back pain; if the lesion is in the lumbar
spine, there is referred pain down one or both legs or to
the hip or groin. As in children, there is localized spinal
tenderness, paravertebral muscle spasm, and limitation
of spinal motion. Neurological impairment is unusual in
children but is more likely in adults, secondary to an
extradural inflammatory reaction with spinal cord or
nerve-root compression. In recent years it has been ob-
served that intravenous drug users appear to be predis-
posed to discitis.

Postoperative disc space infection is also difficult to

diagnose because patients routinely have back pain and
muscle spasm after surgery. However, if the spasm is
severe and prolonged (beyond a matter of weeks), disc

space infection should be considered, despite the ab-
sence of any evidence of wound infection.

CNS INFECTIONS / 207

Diagnostic Procedures

The white blood cell count in children and adults is

often normal or only moderately elevated, but the eryth-
rocyte sedimentation rate is almost uniformly elevated.
Blood cultures are positive in about one-quarter of pa-

tients with pyogenic infection of the disc space; when
positive, the blood culture can be used as a guide for
antibiotic therapy and can obviate the need to/obtain a
culture from the affected disc space.

Plain x-ray films of the involved areas of the spine

show localized disc space narrowing as the first radiologi-
cal sign, but the films may be normal until several weeks
after onset of the symptoms. Narrowing is followed by

blurring of the end plate and irregularity and lytic de-
struction of the subchondral portion of the vertebral
body. In later stages, after many months of healing, there

is sclerosis and spontaneous interbody fusion. Lamino-

grams or CT scans are helpful in characterizing the le-
sion. MRI scanning of disc space infection shows loss of
disc height, irregular disc margins, and increased signal
from the adjacent vertebral bodies (393). Radioisotope
scanning shows a localized area of increased uptake; spot
views using the pin-hole collimator provide greater diag-
nostic detail. The bone scan, however, is of less value in

postoperative discitis, because increased uptake is nor-

mally expected following disc surgery. Reliance in the
diagnosis of postoperative infection is placed on serial

plain x-ray films and CT scans. An experimental study

in animals comparing MRI scanning to radioisotope
imaging in pyogenic infection of the intervertebral disc
revealed that MRI is more sensitive than isotope scan-
ning, particularly in the early stages of the infec-
tion (394).

Percutaneous needle aspiration of the affected disc

space should be seriously considered in an effort to ob-

tain material for culture; identification of the offending

organism is crucial in order to select appropriate antibi-
otics, unless the blood culture has been positive (2). Disc
space culture in children is said to be less vital than in
adults because the organism in children is likely to be

Staphylococcus aureus. A problem with simple needle

aspiration is that the infection is usually not purulent,
and positive cultures are obtained in no more than one-

third of the cases. If no purulent material can be aspi-

rated, 1 to 2 ml of saline may be injected through the
needle and the saline reaspirated. An alternative tech-
nique that yields positive cultures in about two-thirds of
the cases involves use of a trephine biopsy needle, which
can be introduced percutaneously under local or general

anesthesia or as an open surgical biopsy. This can be

done under fluoroscopic or CT guidance. The biopsy/
aspiration technique not only provides tissue for histolog-
ical examination but also increases the likelihood of ob-

taining a positive culture. Histological verification of
infection is valuable in patients in whom an organism is

not isolated; a further advantage is the occasional finding

of an unsuspected tumor. To place the diagnostic proce-
dures in perspective, early radioisotope bone scan and
early biopsy of the affected disc are recommended.

Treatment

The key to management is the administration ofparen-

teral antibiotics for four to six weeks, basing the selection
of antibiotic on blood culture or biopsy/aspirate from
the affected disc space. Although antibiotics have proven
value for the treatment of vertebral osteomyelitis, there
is a question of the effectiveness of antibiotics for disc
space infection. At least in the normal, noninfected disc,
antibiotics do not penetrate the disc (395), but it is not
clear whether penetration may occur in the presence of
discitis. Despite these reservations, the current general
consensus favors use of antibiotics in disc space infec-
tion. Bed rest is recommended for comfort until the
acute symptoms of back pain and spasm subside. Rigid
immobilization in a body cast is probably unnecessary.
After the initial acute phase, the patient is permitted to
ambulate with a simple spinal support for comfort. The

erythrocyte sedimentation rate and plain x-ray films of
the spine monitor resolution of the infection (396).

Children tend to recover over the course of a few

weeks to several months; the course in adults may be
more prolonged. In individuals, usually adults, in whom
the symptoms persist and the x-ray films fail to show
bone healing, open surgical debridement of the disc can
be carried out; a spinal fusion might be added at the time
of the disc debridement. Some authors recommend early

surgical treatment in some cases, which appears to eradi-
cate the disease (390), In the unusual circumstance of

neurological impairment secondary to spinal cord or
nerve root compression, surgical decompression is man-
datory unless there are general medical contraindica-
tions. In general, the long-term outlook for most patients
with disc space infection is favorable.

Pyogenic Spinal Epidural Abscess

In two U.S. hospitals, the incidence of spinal epidural

abscess was between 0.2 and 1.2 per 10,000 admissions
from 1947 to 1974 (397). Acute or chronic forms have
been described, depending on whether the clinical
course evolves over a few days or several weeks. Pyo-

genic epidural abscesses may arise hematogenously or by
spread from adjacent vertebral osteomyelitis.

Etiology and Pathogenesis

Skin infections are the most common antecedent

source (397-399). Staphylococcus aureus is the most

common infecting organism, but streptococci and gram-

negative bacteria from preexistent urinary tract infec-

208 / CHAPTER 10

tions may also be responsible. Spinal trauma occurring

just before the onset of symptoms has been reported in

10 to 40 percent of patients; there is a question whether

small, clinically insignificant, traumatic epidural hema-
tomas subsequently become colonized with bacteria
(397,398).

Epidural abscesses can involve any portion of the

spine, but the thoracic region ismost commonly in-
volved. The pus usually lies dorsally because epidural
fat, which is susceptible to bacterial invasion, lies dor-
sally. The dura is closely'approximated to the vertebral
bodies anteriorly (397,398). Anterior epidural abscesses

were found in 7 of 39 cases reviewed by Baker, Ojemann,

Swartz, and Richardson (397). In acute hematogenous

cases, granulation tissue admixed with pus extends ax-

ially over an average of four spinal segments. Chronic
epidural abscesses tend to have an even more extensive
axial spread than do acute lesions. The dura itself is resis-
tant to bacterial penetration, and spread of infection to

the subdural or subarachnoid spaces is rare.

Intuitively, one would imagine that the space-occupy-

ing effect of the epidural pus compromises the spinal

cord by pressure. Often, however, the neurological in-
volvement appears out of proportion to any observed
pressure effect, and it has been proposed that the neuro-
logical sequelae result from epidural arterial or venous
thrombosis, with resultant spinal cord infarction (400).

Clinical Manifestations

Individuals with acute abscesses are febrile and septic,

but those with chronic processes may be afebrile and

appear relatively well. Spinal epidural abscesses tend to
evolve through four clinical stages: (1) focal spinal pain
and tenderness; (2) root pain; (3) paresis; and (4) paraly-
sis (399). In the acute case, this sequence of events occurs
over an average of seven days, whereas chronic cases

may evolve over weeks or months. Once paresis ensues,

however, total paralysis generally occurs within 24
hours. Because the ultimate quality of neurological recov-

ery varies inversely with the degree and duration of pare-

sis or paralysis, spinal epidural abscess is a true neurosur-

gical emergency. Immediate operative decompression is

mandatory.

If an individual has the classic clinical syndrome plus

evidence of vertebral bone destruction on plain x-rays,
the diagnosis and approximate locus will be highly suspi-
cious for epidural abscess. In acute cases, however, no
osteomyelitis will be evident, and, although the diagnosis

may be suspected, the exact locus may be in question. In

either case, but particularly in acute cases, imaging by

CT scan, MRI, or myelography is indicated in order to
delineate the rostral and caudal spread of epidural pus. If

myelography is carried out, contrast agent may be in-

jected above or below the suspected site of the lesion to

outline the upper and lower limits of the abscess. Care

must be taken when advancing the spinal needle to avoid
introducing bacteria from the epidural to the subarach-
noid space. If a spinal puncture is done and spinal fluid
examined, the CSF may be turbid or xanthochromic.
Pleocytosis may be evident, and the protein level may be

elevated. The glucose is often reduced even in the ab-

sence of meningitis.

The differential diagnosis of spinal epidural abscess

includes meningitis, spinal subdural abscess, acute trans-
verse myelitis, herniated intervertebral disc, vertebral or
spinal cord tumors, and vascular lesions.

Treatment

Antibiotics are started when the diagnosis is suspected

and while the patient is being prepared for surgery. Be-

cause the overwhelming number of cases are due to
Staphylococcus aureus, empirical therapy should begin
with nafcillin unless an alternative etiology is suggested

by history or laboratory findings of an antecedent infec-

tion due to another organism (A. Molavi, Hahnemann
University, personal communication). Pyogenic spinal
epidural abscess is quite amenable to drainage. The sur-
gical approach depends on the location of the abscess in
the spinal canal. At operation, a specimen of pus or gran-
ulation tissue is obtained for gram-stain, aerobic and an-
aerobic cultures, and sensitivities as well as for fungal
and mycobacterial cultures and sensitivities. At surgery,
free pus in the epidural space is drained, and the epidural
space is irrigated with saline/antibiotic solution. Hulme
and Dott recommend excision of chronic granulation

tissue to prevent subsequent dural stricture by scar tissue

(399). In the series of Baker and associates, when a
chronic epidural abscess was found, the laminectomy
wound was closed at surgery, without postoperative diffi-
culties. When an acute pyogenic epidural abscess was
found, the wound was either packed and left open for
subsequent secondary closure or was loosely closed over

soft irrigation catheters that could be used to irrigate the

epidural space with antibiotic solution during the postop-
erative phase (397). Once the specific organism is identi-
fied and its sensitivities determined, a specific antimicro-
bial agent may be selected for further therapy.

Acute hematogenous abscesses are not usually asso-

ciated with vertebral body destruction and spinal instabil-
ity. If vertebral osteomyelitis coexists with body collapse
and gibbus formation has occurred, or if spinal instabil-
ity is present because of the infection, later stabilization

procedures may be necessary.

Prognosis

Before the use of antibiotics, the mortality for epidural

abscess ranged from about 30 to 90 percent (398,399);

CNS INFECTIONS / 209

recent mortality is approximately 18 percent (397). In
general, the neurological outcome depends on the degree
of cord function remaining prior to drainage and decom-
pression. Patients with no paresis or with weakness last-
ing less than 36 hours often have excellent neurological
recovery. Those who have been paralyzed for longer

than 48 hours generally do not recover neurological
function. Baker and colleagues reported on the outcome
(with aggressive diagnosis and surgery) of 32 patients

who survived their epidural abscesses: 4 were perma-

nently paralyzed, 5 had paresis, and 23 were neurologi-

cally intact (397).

Spinal Subdural Empyema

Spinal subdural empyema (abscess) is a rare condi-

tion. In 1984, Probst and Wicki summarized 14 cases
culled from the literature and added three of their own

(401). Analysis of these cases led to the conclusion that

the origin of the subdural infection was most often hema-
togenous but that penetration of the dura from a contigu-
ous epidural infection, lumbar puncture, injury, or con-
genital deformity (e.g., dermal sinus tract) could also
account for the infection. Staphylococcus has been the
most common bacterium; diabetes mellitus is a com-
mon predisposing cause. Thoracic, thoracolumbar, and
lumbar areas were all involved with about equal fre-

quency, and several cases occurred where pus extended

in the subdural space from cervical to sacral areas.

Pathologically, the inflammation may spread into the

subarachnoid space. The arachnoid and dura are thick-
ened. Pus is present subdurally, and granulation tissue is

fixed not only to the dura but also to the spinal cord. The

more acute the case, the greater the amount of pus; the
longer the duration of symptoms, the more likely the

occurrence of granulation tissue. Infection involves the

extra- and intramedullary blood vessels as well. This
leads to vascular narrowing and occlusions, particularly
venous thrombosis and hemorrhagic infarctions. The
nerve roots themselves may be swollen and demyelin-

ated. The white matter of the spinal cord is particularly

involved.

Clinically, patients have fever and generalized signs of

infection. Signs of meningeal irritation may be evident.
There may be back pain and spinal cord (myelopathy) or
radicular symptoms and signs. The neurological findings

may be secondary to interference with blood supply or
may be due to direct neural compression.

Upon lumbar puncture, frank pus may be returned.

Because of compression of the subarachnoid space by

the pus, it may be impossible to obtain CSF. When CSF
is found, it is often xanthochromic; the cell count is gen-
erally elevated. Protein is usually elevated and CSF glu-
cose diminished. Occasionally, however, patients with
subdural abscesses have normal CSF.

Plain x-rays generally show no bone destruction. My-

elography demonstrates an irregular filling defect or a
block that may be undifferentiable from epidural ab-
scess. Surgical decompression is essential. Pus, when
found, is removed by irrigation. If possible, granulation
tissue is removed, but not granulations densely adherent
to the spinal cord. Probst and Wicki also recommend
early rehabilitation and, of course, treatment of any un-
derlying infection (401). Of 15 patients who underwent
surgery, six were cured, five improved, and four died.

Intramedullary Pyogenic Spinal Cord Abscess

Intramedullary spinal cord abscesses are found in ap-

proximately 1 of every 40,000 autopsies. The peak inci-
dence is in the first and third decades; males are more
commonly affected than females. The thoracic spinal
cord is most commonly involved. Among 55 reported

cases, 42 individuals had a single intramedullary abscess,

and the remainder had multiple lesions (402). The pre-
dominant organisms were Staphylococcus and Strepto-
coccus. Midline spinal skin defects, such as dermoid
sinus, and antecedent infections of the respiratory tract,
spine (including fractures), heart valves, genitourinary
tract, or soft tissues had been present in 80 percent of
patients. No apparent infected focus could be found in
the others. Bacteria can reach the spinal cord by (1) di-
rect implantation secondary to trauma, (2) the blood-
stream, or (3) lymphatics from the retropharyngeal
space, mediastinum, or abdominal cavity. Such lym-
phatics course along spinal nerves and communicate
with the spinal subarachnoid space and Virchow-Robin

spaces. Acute intramedullary abscesses are similar to

other central nervous system abscesses, but they lack the
widespread venous infarction seen with epidural ab-
scesses. This may account for their often favorable prog-
nosis.

Clinically, intramedullary abscesses can have an

acute, subacute, or chronic course. Neurological symp-
toms and signs vary according to abscess location. Acute
cases have fever, and there may be transverse myelitis.
Pain in the neck or back, urinary incontinence, dysesthe-
sias, and monoparesis that progresses to paraparesis or
quadraparesis typically occur. Patients with chronic in-

tramedullary abscesses have a stuttering course simulat-
ing that of a spinal tumor. Examination of the cerebrospi-
nal fluid is generally unrewarding and may be
misleading; pleocytosis may suggest meningitis. Myelog-
raphy may demonstrate a spinal block and suspicion of

an intraspinal mass.

Surgical therapy consists of laminectomy and incision

and drainage of the abscess. Occasionally, an intraspinal
abscess will masquerade as arachnoiditis, and, therefore,
when localized spinal arachnoiditis is discovered during

210 / CHAPTER 10

spinal cord surgery, this should raise suspicion that a
spinal cord abscess may be present. As in the case of
abscesses in general, antibiotics are started as soon as
infection is recognized. When obtained, the pus is gram-
stained and cultured for aerobic, anaerobic, and myco-

bacteria as well as fungi for selection of specific antimi-
crobial therapy. Postoperatively, patients are followed
closely because of a high recurrence rate. Twenty of the

55 patients cited above had drainage of the intramedul-

lary abscess; of these, five patients died (all before the
advent of antibiotics), six recovered neurologically, six

showed some improvement, and three remained un-
changed.

Spinal Tuberculosis

Tuberculosis may involve the vertebral column and

the epidural space, dura, arachnoid, or spinal cord
(206,342,403). Often, the disease is confined to one ana-
tomic area (404).

Tuberculous Spondylitis (Pott's Paraplegia)

Generally, tuberculous spinal infection involves the

vertebral body (Pott's tuberculous spondylitis). Tuber-
culous destruction of the spine, with subsequent spinal
cord compression, continues to be a common disease in

developing nations. Mathai and Chandy indicated that

in India, 42 percent of their spinal operations for non-

traumatic paraplegias were for compression consequent
to tuberculous spondylitis (404). In the United States,
this disease is rare. Tuberculous spondylitis most fre-

quently involves the lower thoracic and upper lumbar
vertebrae. The disease most commonly affects the verte-

bral body and is usually limited to one vertebra. Neuro-

logical complications occur in 10 to 25 percent of pa-

tients, particularly if the thoracic spine is involved.
There are two categories of Pott's paraplegia: early-onset
cases, in which the neurological dysfunction begins
within two years of the tuberculous spondylitis; and late-
onset paraplegia, with the deficit beginning after two
years. Early cases occur when the disease is active,

whereas late cases are associated with a recurrence of the

infection following apparent quiescence.

The disease usually starts in the first decade of life but

becomes symptomatic and is diagnosed during the third

decade. A case has been reported of spinal tuberculosis

after a closed fracture (405); the trauma appeared to pre-
dispose the involved vertebrae to hematogenous infec-
tion. Though no distinctive pattern of neurological signs
or symptoms exists with Pott's disease (216), pain and
local spine tenderness occur in more than 70 percent of
patients. Radicular pain is common. The cause of the
cord compression may be epidural abscess, bony com-
pression, or both.

Radiographically, early vertebral body decalcification

is seen about the disc with slight diminution of the disc
space. Later, frank vertebral erosion and collapse occur,
and paravertebral or psoas abscess may appear. Sclerotic
changes may also be present because of concomitant
bone regeneration and fusion of vertebral bodies. Casea-
tion beneath the anterior spinal ligament causes scallop-
ing of the anterior vertebral border. CT scanning shows
the expected vertebral body involvement but, in addi-
tion, can depict paraspinal abscess and an epidural tu-
berculous collection. Contrast enhancement may aid in
their delineation. CT is also helpful for guiding aspira-

tion of suspected areas of infection (406). Myelography
often reveals a block at the infection site.

Spinal tuberculosis can be treated medically or surgi-

cally. Friedman treated 64 patients with Pott's disease by

- prolonged administration of antituberculous drugs, bed

rest, and spinal bracing (406). Spinal fusion was not
done, and laminectomy was reserved for eight patients

with paresis. Fifty patients were cured by this approach,
but 10 others had relapses, and four died. Hodgson and

. Stock, on the other hand, advocate direct operative at-

tack on tuberculous vertebrae (407). The diseased bone
is approached anteriorly or laterally and is resected.
Granulation tissue around the dura is stripped away, and
the vertebral bodies are stabilized by strut grafts. They
report improved neurological function even in cases
with paralysis. In 1960, they reported the operative re-

sults on 35 paralyzed patients. Twenty-six had complete

neurological recovery after operation. Graft complica-

tions (slippage, fracture, angulation) occurred in 13 pa-
tients, and four died. Subsequently, Hodgson and col-
leagues also reported that 19 of 23 paraparetic children
made complete neurological recoveries after decompres-
sion and fusion, including 19 of 20 who had been para-
lyzed (408). Antituberculous drugs are given for at least

18 months after operation. It would appear that Hodg-

son's patients had more serious bony and neurological
involvement than did Friedman's.

Hsu and Leong reported treatment of 40 patients with

tuberculosis of the cervical spine (409). Forty-three per-

cent of the patients had evidence of cord compression,

mainly from pressure by epidural abscess. Surgical ther-
apy was generally by anterior excision of the diseased
bone, followed by grafting. In addition, all patients re-
ceived streptomycin for three to nine months. All pa-
tients recovered spinal cord function. Four patients un-
derwent posterior fusion initially, but all eventually
required anterior excision and grafting because of pro-
gressive kyphosis or persistence of vertebral body infec-

tion. Laminectomy, therefore, is not recommended for

Pott's paraplegia because the cord is compressed from its
anterior aspect. However, in 10 percent of cases, tuber-
culous spondylitis involves the neural arch instead of the
body. In the latter situation, the spinal cord may be com-
pressed from its dorsal aspect instead of anteriorly. Ra-

CNS INFECTIONS / 211

diographically, such cases may be mistaken for epidural

metastasis. Patients with neural arch involvement invari-

ably have associated dorsally placed epidural abscesses
and are best treated by laminectomy and antituberculo-
sis therapy (410).

Tuli reported on the results of aggressive medical and

surgical therapy in 200 cases of spinal tuberculosis (411).
Medical treatment for adults consisted of streptomycin,
sodium para-aminosalicylate, and isoniazid. Patients
were placed on a firm bed or used a plaster jacket. Grad-
ual mobilization of the patient in a spinal brace was be-
gun after six to nine months. Paravertebral abscesses
were aspirated or drained. Decompression of the cord

was eventually performed on patients on medical ther-

apy who failed to show progressive recovery of neurologi-

cal function. Ninety-four percent of the patients without
neurological deficit recovered without surgery, and 38
percent of those with neurological involvement also re-

covered without operation. According to Kaufman,

Kaplan, and Litman, only 5 to 20 percent of cases of
Pott's disease are complicated by neurological defi-
cit (412).

The regimen of choice for tuberculosis is a combina-

tion of isonazid, rifampin, and pyrazinamide for two

months followed by a four-month or longer course of
isonazid and rifmapin.

A 10-year study of 283 cases of spinal tuberculosis in

children in Korea showed that antituberculous chemo-

therapy resulted in satisfactory outcome in 88 percent of

the patients (413). There was no benefit from immobili-
zation either by bed rest or use of plaster of Paris jacket.

Intraspinal Tuberculosis

Intramedullary spinal tuberculomas occur much less

frequently than cerebral tuberculosis (205,206,403). Al-
though some intramedullary tuberculomas are primary,
others occur in association with cerebral tuberculomas.
In addition to paraplegia resulting from the direct effects
of infection, tuberculous arachnoiditis and associated
vasculitis also may produce neurological sequelae. Das-

tur reported that three of six patients in whom spinal

tuberculomas were excised made good neurological re-
coveries (206).

Tuberculosis of the coverings of the spinal cord in-

clude arachnoiditis, subdural granulomas, and extra-
dural granulomas. Tuberculous arachnoiditis is seen in
patients who, in the past, suffered from tuberculous men-
ingitis or pulmonary tuberculosis. Thick, densely orga-
nized exudates may encase the entire length of the spinal
cord and may cause arteritis and secondary vascular
changes leading to "transverse myelitis" or motor loss.
Excision of local arachnoidal granulomas may provide
some relief (201).

Subdural tuberculous granulomas are generally dif-

fuse; the dura is thickened diffusely, and the granuloma

surrounds the spinal cord. Some authors prefer to relieve

the compression surgically, but others recommend ste-

roids and antituberculous drugs.

Occasionally, tuberculous epidural granulomas com-

press the spinal cord but are unassociated with any bony
changes. Lacking the usual bone changes associated with

tuberculosis, such patients may be misdiagnosed and

therefore mismanaged. Myelograms demonstrate a
block. These epidural granulomas (tuberculomas) are
dorsally placed, and, again, laminectomy and antituber-
culous drugs are indicated (410).

Kaufman, Kaplan, and Litman reported seven cases

of tuberculous spinal epidural abscess (412). These pa-
tients had back pain for an average of about three
months. No patient had leukocytosis, and only one had a
fever greater than 100°F. Tuberculous skin tests were
positive in only five of the seven. All showed disc space
or vertebral body involvement, or both. The spinal ab-
scesses contained fibrous granulomas with caseation ne-
crosis. Five of the seven patients demonstrated acid-fast

bacilli on stain and grew out Mycobacterium tuberculo-
sis. All seven underwent surgery; three died in the postop-

erative period.

Parasitic Spinal Infection

Spinal Echinococcosis

Hydatid disease caused by Taenia echinococcus rarely

involves the spine. The cchinococcal embryo is carried
to a vertebral body, infiltrates, and destroys bone (414).
Thoracic and lumbosacral vertebrae are most com-
monly involved. The parasite incites little defensive tis-
sue reaction, and adjacent bones, such as the ribs or pel-
vis, can be invaded. The intervertebral disc is preserved.

Spinal cord impingement occurs as the unencapsulated

parasite invades the spinal canal or as collapsed bone

compresses the cord. Clinical progression of the disease

is slow because the parasite enlarges slowly. The com-
mon signs and symptoms are pain, motor and sensory
deficits, difficulty with bowel and bladder function, par-
avertebral swelling, and gibbus formation; paraplegia
may occur. CT scanning shows bony destruction, extra-

dural isodense mass, and paraspinal extension of the dis-

ease (415).

Spinal decompression by an anterior (416) or poste-

rior laminectomy approach (417) is carried out, depend-
ing upon location of the neural compression within the
spinal canal. Pathologically, the cyst fluid contains the
typical hooklet-bearing scolices, and the cyst wall is com-
posed of layers of chitin typical of echinococcosis. Irriga-

tion of the wound with hypertonic saline for five minutes
may help destroy the residual organisms. Occasionally,
total vertebrectomy is necessary. Mebendazole has been
used in conjunction with surgery in the treatment of spi-
nal hydatid disease (418). Postoperative use of mebenda-
zole has been reported as being effective (417).

212 / CHAPTER 10

Spinal Schistosomiasis

The infestation can occur as a space-occupying, intra-

medullary mass, which can extend to involve the cauda
equina (283). It may present clinically as an acute trans-
verse myelitis, causing destruction and atrophy of the
cord, or as a progressive neurological process with slow
progressive flaccid paralysis. Males are predominantly
affected. In endemic areas, spinal schistosomiasis is con-

sidered in any patients presenting with spinal cord symp-

toms. Treatment consists of decompressive spinal sur-
gery and schistosomicidal drugs, which kill the adult
female worms and diminish the inflammatory response.
Praziquantel and oxaminquine are the current drugs of
choice; they are administered orally and are relatively

safe (419).

Spinal Cysticercosis

Spinal cysticercosis (420,421) resulting from infesta-

tion with the pork tapeworm occurs in only 2 to 5 per-
cent of all cases of neurocysticercosis. Although this
form of the disease can occur independently of brain

involvement, it usually results from downward spread of

intracranial parasites. The cysts may be intramedullary
or subdural. Associated arachnoiditis is common. Spinal
involvement, though rare, can result in vertebral col-
lapse and spinal cord compression (422).

Guinea Worm (Dracunculus)

Infection with the worm Dracunculus medinemis is

endemic in Africa and Asia. Rarely, this worm may
lodge in the vertebral extradural space, causing paraple-
gia. The associated inflammatory process is of a low-

grade, chronic nature, but the onset of neurological

symptoms may be sudden and abrupt. Preoperatively,
diagnosis is rarely made because the clinical course is
indistinguishable from many other extradural spinal in-
fections. Known prior guinea worm infection, periph-
eral blood eosinophilia, and extraspinal calcined lesions
indicating the dead guinea worm may aid diagnosis
(423). The infecting worm causes spinal cord signs, and
myelography reveals a block. The worm is discovered in
chronic granulation tissue and pus at laminectomy.
About half of the patients who are operated on improve.
Niridazole, specific for guinea worm, has been recom-
mended (424).

Fungal Spinal Infection

Spinal Blastomycosis

Spinal blastomycosis mainly affects the thoracic and

lumbar vertebrae. Clinically and radiologically, blasto-

mycosis may be confused with tuberculosis, and the two

diseases may coexist. Accurate tissue or culture diagnosis
of the lesion must be made for appropriate treatment
with amphotericin B.

Candida

Fungal infection of the spine with Candida, although

rare, tends to occur in patients after prolonged hospital-
ization for complex medical problems. Broad spectrum
antibiotics and parenteral hyperalimentation have been
reported as predisposing factors of Candida infection in
general (425). Amphotericin B is effective for treatment
of Candida vertebral osteomyelitis (426). Surgical de-
compression is carried out when there is evidence of spi-
nal cord compression (427).

Spinal Nocardiosis

Rarely, Nocardia, a gram-positive bacteria, spreads he-

matogenously from the lungs to the vertebral bodies and

epidural space and may result in spinal cord involve-
ment. Spinal nocardiosis is treated as any focal spinal
infection. A bacteriological specimen must be obtained
for diagnosis. Surgical decompression by an anterior or
posterior approach depends on the site of the infection in

the spinal canal.

CONCLUSION

The essential ingredient in management of focal CNS

infection is neither medical nor surgical, but rather a

combination of antimicrobial administration and ju-

dicious surgical intervention. Advances in spinal surgery

enable multiple approaches to the spine that facilitate
precise decompression as well as fusion where necessary.
The antimicrobial aspects—with the multiplicity of fac-
tors of organism identification, antimicrobial susceptibil-
ity, and host resistance—afford wide latitude in selection
of an antimicrobial regimen. Further improvement in
therapeutic outcome can be anticipated by meticulous

bacteriological processing and by the application of ex-
isting knowledge of antimicrobial therapy.

Many of the conditions involving infection of the ner-

vous system have associated systemic manifestations.
Consequently, management of patients with these dis-
orders is best achieved through a multidisciplinary team
effort. This is particularly exemplified by AIDS, which

consists of a broad spectrum of disorders, so that team
management is essential.

ACKNOWLEDGMENTS

This chapter is a revision of previous publications by

the authors, particularly references 428 through 431.

The assistance of Mary F. Boylan, B.A., and Daniel O.

CNS INFECTIONS / 213

Walsh, B.A., Research/Editorial Assistants in the Depart-
ment of Neurosurgery, Hahnemann University, in the
preparation of the manuscript is gratefully acknowl-
edged. John Molavi, M.D., Chairman of the Division of

Infectious Diseases, Hahnemann University Hospital,

reviewed those aspects of the manuscript relating to anti-
microbial therapy.

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