This is a 12-month old male in previously good 
health presenting to a clinic with a history of fever for 
two weeks (highest recorded temperature 39.1 
degrees).  The fevers were initially attributed to 
teething.  There is a dry, nonproductive cough for one 
week.  He has had a decreased appetite, but no 
vomiting or diarrhea.  Yesterday, he was noted to be 
lethargic with decreased movement of his right arm and 
left leg.  His eyes would also roll.  This morning, an aunt 
came over to the home and found him to be quite 
somnolent, poorly responsive and with abnormal 
twisting movements of his extremities.  This aunt 
immediately brought him in to the nearest clinic.
     Exam:  T 37.3 (axillary), HR 165, RR 20, BP 143/93.  
He is well developed and well nourished.  He is tired 
appearing, sometimes listless and somnolent.  There is 
no spontaneous movement of the entire right side of his 
body.  He has a modest left facial droop.  Pupils are 5-6 
mm bilaterally, sluggishly reactive to light, with  
intermittent nystagmus.  TM's unremarkable.  His head 
is turned to the left, with resistance felt when passively 
rotating his head to the right (refuses to bring his chin to 
the midline).  Neck difficult to assess for rigidity.  Heart 
regular, no murmurs.  Lungs clear.  Abdomen benign, 
scaphoid,  no palpable masses, tenderness or 
hepatosplenomegaly.  Extremities slightly cool, pulses 
somewhat diminished, but normal capillary refill time.  
Skin clear.  DTR's 2+ bilaterally.  He holds his left leg 
extended.  His right hip is flaccid with the ipsilateral 
knee in fixed flexion.  With noxious stimuli, he does not 
withdraw from pain at the right leg or right arm.  His left 
leg and left arm react normally.  His plantar reflexes are 
downgoing bilaterally.

     A CT of the brain is immediately ordered.

View CT.  

     These two cuts from his CT scan series show 
multiple 2-3 cm diameter loculated cystic lesions 
consistent with multiple abscesses (dark areas with 
rims of enhancement).  There is distention of the 
posterior fossa with a midline shift toward the right.  
There is no sign of cribiform fracture or mastoiditis.
     He is admitted to the intensive care unit where 
infectious disease and neurosurgical consultations are 
obtained.  His initial work-up includes a CBC and 
chemistry.  A chest radiograph and an abdominal 
radiograph are performed to look for signs of other 
abscesses.
     Admission labs:  Na 141, K 3.4, Cl 99, bicarb 25, 
gluc 127, Ca 10.3, phos 5.3, Alb 3, SGPT 8, SGOT 22, 
BUN 10, creatinine 0.2.  WBC 23.2 (49% segs, 14% 
bands, 7% monos, 28% lymphs). Hgb/Hct 9/37.  
Platelets 474,000.  His chest radiograph is normal.

View abdominal flat plat.

     An open safety pin is noted in his abdomen.

     Shortly after admission, he developed seizures.  He 
was treated with anticonvulsants, cerebral dehydration 
and controlled hyperventilation.  Approximately 12 cc of 
foul smelling, thick, yellow-green, purulent material was 
needle aspirated through the lambdoidal suture.  Gram 
stain showed gram positive cocci in clusters, chains and 
pairs.  A burr hole was drilled into the right suboccipital 
area, and a large posterior fossa abscess was aspirated 
for yellow, creamy, opaque fluid.  A left brain abscess 
was visualized by ultrasound and needle aspirated for 
85 cc of purulent material sent for culture.   He was 
initially started on ampicillin, clindamycin, and 
gentamicin.  His initial culture grew peptostreptococcus, 
fusobacterium and alpha hemolytic streptococci, all of 
which are oral bacteria.  His antibiotics were changed to 
vancomycin, ceftazidime, metronidazole, tobramycin, 
and chloramphenicol.

     Two days after admission, a follow-up abdominal 
radiograph is obtained.

View follow-up abdominal film.

     This abdominal film shows the safety pin to be 
broken into two pieces now.  It has not moved much.  
There is residual barium in the bowel from a previous 
contrast study which was unremarkable.  Two weeks 
later, the safety pin fragments are no longer seen.
     An echocardiogram to rule out cardiac vegetations 
showed a possible  left atrial appendage lesion.  A 
repeat echo was normal, with no definite evidence of 
left atrial mass.
     His overall clinical progress was poor.  Follow-up CT 
scans showed recurrent abscesses and progressive 
cerebral atrophy. 
     How the safety pin relates to his brain abscesses is 
unclear.  Cultures of the brain abscesses were not 
positive for bowel organisms, but rather oral flora.  
Perhaps the safety pin caused a perforation somewhere 
in his pharynx or esophagus as it was going down.

Discussion
     The first reference to brain abscess was made by 
Hippocrates in 460 B.C.  Farre recognized brain 
abscess as a complication of congenital heart disease 
in 1840.  The first operative treatment of brain abscess 
was by Dupuytren in 1889.
     Brain abscesses are the most frequent intracranial 
suppurative process occurring in children, the 
pathogenesis of which depends upon predisposing 
conditions that also influence the anatomic location of 
the abscess.  The transmission of infection may occur 
by continuity, as with penetration of the dura, or by 
contiguity or juxtaposition.  The membranous cranial 
bones are formed from both dura and galea; therefore, 
they derive their blood supply from both structures.  
This intracranial/extracranial vascular connection 
explains the mechanism for the development of cortical 
thrombophlebitis.  The diploic veins of Breschet are 
valveless; therefore, blood may flow in either direction 
and bacterial infection or septic emboli may gain access 
intracranially.  Cranial bone defects may occur and can 
be either acquired or congenital.  The posterior wall of 
the frontal sinus, which is normally about one half the 
thickness of the anterior wall, may be eroded by a 
mucocele, infection, or neoplasm, or it may sustain 
disruption due to trauma.  The epidural space may 
become infected in the dehiscent area, with abscess 
formation and possibly secondary intracranial spread 
throughout the dura.
     Chronic otitis media, mastoiditis, meningitis and 
congenital heart disease are the most common 
predisposing factors, accounting for about 60% of brain 
abscesses in children.  Contiguous spread from ear, 
nose or throat infections usually results in a single 
abscess formed in proximity to the infected area, i.e., 
frontal abscess arising from ethmoid sinusitis, or 
temporal or cerebellar abscess arising from mastoid 
infection.  The average age of these children is 5 to 10 
years.  Extension occurs via anastomosing veins.  
Purulent material can also drain directly from an 
infected sinus through the cribiform plate of the frontal 
bone into the subdural space.  Meningitis as a cause is 
more common in children less than 2 years of age.
     About 2% of children with cyanotic congenital heart 
disease (i.e., right to left intracardiac shunts, pulmonary 
arteriovenous fistulas) develop brain abscess.  
Tetralogy of Fallot is the most common heart defect 
leading to brain abscess formation.  Infection is usually 
with alpha-hemolytic streptococci.  Organisms with a 
predilection for hypercarbic/hypoxic areas have been 
isolated.  Mixed infections are uncommon. 
     Odontogenic (i.e., dental abscess), as well as 
massateric space and infratemporal infections may be 
the primary site.  Head trauma (i.e., skull fracture), or 
penetrating head injury are known risks for brain 
abscess.  P. multocida must be considered in a skull 
penetrating dog bite.  Ocular trauma (i.e., orbital roof or 
temporal bone fracture) with wooden toys has been 
associated with cerebral abscesses.  In such cases 
there is a male to female ratio of 3:1, with the most 
common item being a graphite pencil.  Wood, as a 
penetrating agent carries a high risk of infectivity and 
fragmentation.  MRI may be needed to identify the 
foreign body. 
     Abscess due to hematogenous spread (i.e., from 
endocarditis, osteomyelitis, etc.), is usually along the 
distribution of the middle cerebral artery in the posterior 
frontal or parietal regions.  Immunosuppressed patients 
are also at risk.  The presence of a ventroculoperitoneal 
shunt increases the risk of infection by S. epidermidis 
and S. aureus.
     Citrobacter diversus or Proteus must be considered 
in neonates with multiple brain abscesses.  The 
susceptibility of newborns to Gram-negative infection is 
well established, and is explained by the deficiency of 
both placentally transferred IgM antibodies and 
complement.  The physiological right to left shunt of the 
neonatal blood circulation could explain the colonization 
of the brain during septicemia.
     No discernible underlying disease or source of 
infection can be found in 30% of pediatric brain abscess 
patients.  In adults, pulmonary disease is the most 
frequent cause for dissemination.  This is not true for 
children.
     Anatomic sites of infection are associated with 
certain organisms.  Frontal lobe abscesses (the most 
frequent, 37%) are usually due to sinusitis, and usually 
include aerobic and anaerobic streptococci, S. aureus, 
S. pneumoniae, and H. flu.  Cerebellar (2%) and 
ipsilateral temporal lobe abscesses (11%) are usually 
due to otitis media or mastoiditis.  Common entities 
include  S. pneumoniae, H. flu, Enterobacter and B. 
fragilis.  Temporal, frontal and parietal lobe abscesses 
(28%) have been associated with congenital heart 
disease.
     Multiple abscesses usually arise from meningitis, 
pulmonary and VP shunt site infections, as well as 
congenital heart disease.  In the case of congenital 
heart disease, abscesses usually arise along the 
distribution of the middle cerebral artery.  VP shunt 
infections can involve S. aureus, S. epidermidis, Gram 
negative enteric rods, and P. aeruginosa.  Staph aureus 
is the most common organism in brain abscesses due 
to head trauma or surgical events.  Enterobacter and 
anaerobes can spread from intra-abdominal or 
genitourinary sites.

Pathogenesis
     Focal areas of ischemia or necrosis (i.e., due to 
suppurative vasculitis, hypoxic episode, embolism, 
hyperviscosity, etc.) are a prerequisite for invasion by 
microorganisms because the brain parenchyma is 
resistant to infection.  In addition to epidural or cerebral 
abscess, the same mechanism applies to subdural 
empyema as well as septic thrombophlebitis of the 
emissary cortical veins or venous sinuses. 
     Four stages are recognized in the development of 
brain abscesses.  The first stage (early cerebritis) lasts 
1-3 days, and is characterized by perivascular cuffing 
with inflammatory cells in the region surrounding the 
developing necrotic center, with marked cerebral 
edema developing peripherally.  During this cerebritic 
stage (pre-encapsulation), antibiotics may still be able 
to halt abscess development.  The second stage (days 
4 to 9) is characterized by early capsule formation via 
fibroblasts, as well as neovascularization.  The third 
stage (days 10-13) shows definite capsule formation 
with concomitant increase in fibroblast numbers, as well 
as shrinkage of the necrotic center and diminishing 
cerebritis.  In the fourth stage (days 14 on), a well 
defined necrotic center and a dense collagenous 
capsule with peripheral cerebral edema can be seen. 
The degree of symptomatology is a poor indicator of 
whether the intracranial infection is still in the cerebritic 
stage or has become encapsulated.

Clinical Presentation
     The most prominent clinical manifestations of brain 
abscesses result from space-occupying effects in the 
rigid cranial vault.  Expansion of the lesion, bacterial 
breakdown products, or macrophage induced cerebral 
edema may result in increased intracranial pressure 
and subsequent potentially lethal uncal or brainstem 
herniation.  The "classic" triad of fever, headache and 
focal neurological deficits occurs in less than 50% of 
patients (28% in one study; Saez-Llorens, 1989).  
Seizures, and lethargy are common, as are hemicranial 
headaches, alterations in consciousness, nausea, and 
vomiting.  Papilledema, ataxia and aphasia were also 
reported.  Sixth nerve palsy may indicate increased 
intracranial pressure.  Infants frequently present with 
fever, meningismus, and/or a full fontanelle. 
     Symptoms can also depend upon the anatomic 
sites, i.e., cerebellar abscess presenting with 
nystagmus, ataxia, vomiting and dysmetria.  The frontal 
lobe is thought to be a neurologically silent area, and 
thus abscess formation may not result in focal signs.  
Subtle affective changes, behavioral problems, abusive 
and profane language, depression, or euphoria may be 
more indicative of changes in this area. 

Differential diagnosis
     The differential diagnosis is extensive.  Infectious 
entities include viral encephalitis (especially herpes 
simplex virus), subdural empyema, epidural abscess, 
pyogenic meningitis, tuberculoma, cysticercosis, 
echinococcosis, and cryptococcosis.  Non-infectious 
entities include primary and metastatic brain tumors, 
subarachnoid or intracerebral hemorrhage, central 
venous thrombosis, cerebral infarct, mycotic aneurysm, 
chronic subdural hematoma, hemorrhagic 
leukoencephalitis, or migraine.

Lab findings
     Lumbar puncture is contraindicated due to the risk of 
cerebral herniation.  Cerebrospinal fluid is a poor source 
for isolating the organism (positive cultures in only 7%; 
Saez-Llorens, 1989), unless the abscess ruptures in to 
the ventricular system, in which case the CSF WBC 
count may be greater than 50,000 with a predominance 
of polymorphonuclear cells.  The CBC may reflect 
peripheral leukocytosis with neutrophilia.  Blood cultures 
may be sterile.  Electrolytes are generally normal, 
unless hyponatremia suggests the development of 
SIADH.

Diagnostic Imaging
     Between 1960 and 1974 the techniques used to 
diagnose brain abscess included 
pneumoencephalography, ventriculography, carotid 
arteriography and nuclear brain scan.  Since 1984, CT 
of the brain has been the principal diagnostic technique.  
Computed tomography remains the study of choice, as 
it can discern the number, size and locations of 
abscesses with a high degree of sensitivity and 
specificity.  A brain abscess usually appears as a 
hypodense center with a surrounding ring which can be 
contrast-enhanced.  Other patterns include nodular 
enhancement, and areas of low attenuation without 
enhancement.  The degree of enhancement is thought 
to correlate with the degree of perivascular 
inflammatory cell infiltration and neovascular 
proliferation.  Delayed films with an assessment of the 
degree of enhancement in the center of the lesion may 
differentiate between cerebritis (medical management 
possible) and true encapsulated abscess (surgical 
intervention more likely needed), the latter showing a 
paucity of central contrast. 
     Skull films may show bubbles (pneumocephalus) 
from gas-producing organisms within an abscess cavity 
or outside the cranium.  An electroencephalogram may 
localize a focal lesion as opposed to a more generalized 
lesion such a encephalitis.  Seizure activity and diffuse 
encephalopathic patterns have been reported.  Low 
frequency delta waves commonly signify a cerebral 
abscess (slow wave foci).  A brain scan should be 
considered for patients with a negative CT if  there is 
still a strong suspicion of a brain abscess.  Cerebral 
arteriograms have demonstrated avascular masses.

Management
     The origin of the infection can dictate the choice of 
initial antibiotic treatment.  An initial trial of antibiotic 
therapy may be warranted in patients who are 
considered poor surgical candidates, have multiple 
abscesses or abscesses in deep or difficult anatomical 
locations, concomitant meningitis, or whose abscess 
size is less than 4 cm or considered to be in the 
cerebritis stage. 
     Extensions of ENT infections can be treated with 
penicillin (strep coverage, including S.milleri),  
chloramphenicol (anaerobic coverage, high abscess 
penetration), metronidazole (bactericidal for most 
anaerobes, high abscess penetration, occasionally 
achieving abscess concentrations greater than serum, 
not degraded in purulent debris), or cefotaxime (active 
against Hemophilus, Enterobacter, strep and staph). 
     Penetration is increased in infected tissue.  
Nonetheless, penicillin-susceptible bacteria can be 
cultured from abscesses for prolonged periods despite 
antibiotic therapy.  Inactivation of antibiotics may occur 
by bacterial or leukocytic enzymes accumulating in the 
purulent material trapped by the encapsulation, 
subtherapeutic concentrations within the capsule, or 
antagonism in the case of multiple antimicrobial agents.
     Infection from head trauma or cranial surgery 
warrants an antistaphylococcal agent, e.g. nafcillin.  
Vancomycin is indicated when methicillin-resistant S. 
aureus is prominent.  With the exception of B. fragilis 
and some other anaerobic strains, most of the 
anaerobic pathogens are sensitive to penicillin.  
Ampicillin is inadequate for empiric treatment because 
of the increasing frequency of resistant E. coli and 
Proteus spp., as well as unreliable penetration.  
Aminoglycosides do not penetrate well into brain 
abscesses, and they have reduced activity in the 
anaerobic/acidic conditions associated with purulent 
material.  A beta lactamase-resistant penicillin, e.g., 
nafcillin, oxacillin or methicillin versus S. aureus, should 
be added to metronidazole to cover aerobic and 
microanerophilic streptococci.
     Third generation cephalosporins are options for 
treatment, given their efficacy against Gram negative 
bacillary infection, broad coverage, high degree of 
activity, and  action against S. pneumoniae and H. flu.  
Ceftazidime penetrates the subarachnoid space and is 
active against P. aeruginosa.  Older cephalosporins, 
clindamycin and erythromycin have generally been 
inadequate at achieving therapeutic concentrations.
     Trimethoprim-sulfamethoxazole may cover aerobic 
Gram-positive and Gram-negative rods.  
Chloramphenicol may be bactericidal against S. 
pneumoniae, Hemophilus spp. and most of the obligate 
anaerobes including B. fragilis, but bacteriostatic 
against S. aureus and Enterobacter.  Direct instillation 
of antibiotics in the abscess cavity during aspiration has 
been reported, but efficacy of this technique has not 
been formally assessed.
     Corticosteroid use is controversial.  It is thought to 
retard the encapsulation process, as well as decrease 
endothelial permeability of vessels associated with the 
inflammatory reaction, and thereby reduce the amount 
of brain water.  However, it may increase necrosis, 
reduce antibiotic penetration into the abscess, and alter 
CT scan images of ring enhancement.  Steroid therapy 
can also produce a rebound effect when discontinued.  
Thus, corticosteroid use to reduce cerebral edema 
should be as short a course a possible.
     The duration of treatment depends upon the 
patient's clinical response, imaging findings, 
organisms isolated, and the extent and type of surgical 
drainage, if any.  For those patients undergoing 
excision, 7 to 10 days for parenteral therapy has been 
suggested.  Three to four weeks are probably required 
for patients treated with aspiration, and a minimum of 4 
weeks for those treated with antibiotics alone.

Surgical management
     Debate continues as to whether excision of the 
abscess wall is preferable to single or multiple 
aspirations of the cavity.  The latter appears to be 
preferred in children, on the basis of comparable 
mortality rate and of less potential damage to the brain 
tissue from surgical trauma.  Aspiration is used for brain 
abscess in early infancy, in large abscesses with poor 
capsule formation and in most centrally or deeply 
located abscesses.  Stereotaxic aspiration or aspiration 
guided by operative neurosonography is performed in 
deep hemispheric abscesses or multiple abscesses 
with an intracranial mass effect.  If the patient has 
increasing neurologic deficit, including deteriorating 
consciousness or signs of increasing intracranial 
pressure, surgery is necessary.
     The predominant mode of surgical therapy was 
craniotomy with abscess resection.  Intraoperatively, it 
is important to prevent ventricular or leptomeningeal 
contamination.  Biopsy of brain tissue may be 
necessary if mucormycosis or neoplasm is suspected.

Complications
     The mortality rate of brain abscess varies in the 
literature from 11 to 53%, and is increased with 
increased duration of symptoms before medical 
intervention, coma on admission, young age, larger 
abscess size, multiple abscess, and rupture into the 
cerebral ventricles or subarachnoid space.  
Improvements include the use of CT scanning, 
improved methods for isolating anaerobic flora, and 
more effective antimicrobial treatment.  Morbidity is 
increased in patients who undergo aspiration, rather 
than evacuation or resection. 

Sequelae
     Neurological sequelae (seizure disorders, 
hemiparesis, optic atrophy, spasticity, cranial nerve 
palsy, hydrocephalus, behavior disorder, school 
learning disabilities) can be present in up to 60% of 
patients.  Conversely, complete recovery has been 
reported in 40% of patients.  The incidence of 
neurologic sequelae has been lower when abscesses 
were aspirated (facilitated greatly by CT) rather than 
excised. 
     Serial CT scans are the mainstay of clinical 
follow-up, especially after antibiotics therapy is 
discontinued.  A suggested regimen for serial CT's  is 
every 2-4 weeks until resolution of the lesion, then at 
2-4 month intervals for 1 year.  Successful therapy 
would be indicated by a progressive decrease in the 
degree of ring enhancement, edema, mass effect, and 
size of the lesion.

References
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1985, pp. 324-328.
     Patrick CC, Kaplan SL.  Current concepts in the 
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Intracranial abscesses secondary to nasal, sinus, and 
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