See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/322142049

Brain Abscesses: An Overview in Children

Article · December 2017

DOI: 10.1055/s-0037-1615786

CITATIONS READS

0 360

4 authors, including:

Andrzej Krzysztofiak Maia De Luca

Ospedale Pediatrico Bambino Gesù 27 PUBLICATIONS   78 CITATIONS   
56 PUBLICATIONS   605 CITATIONS   
SEE PROFILE
SEE PROFILE

Alberto Villani
Ospedale Pediatrico Bambino Gesù
165 PUBLICATIONS   1,232 CITATIONS   

SEE PROFILE

Some of the authors of this publication are also working on these related projects:

Pediatric Spine Infection View project

Novartis Influenza Project View project

All content following this page was uploaded by Andrzej Krzysztofiak on 15 February 2018.

The user has requested enhancement of the downloaded file.

 Review Article

Brain Abscesses: An Overview in Children

Andrzej Krzysztofiak1 Paola Zangari1,! Maia De Luca2,! Alberto Villani1

1 Unit of Pediatric and Infectious Diseases, Academic Department of Address for correspondence Andrzej Krzysztofiak, MD, Unit of
Pediatrics, Children’s Hospital Bambino Gesù, Rome, Italy Pediatric and Infectious Diseases, Academic Department of
2 Unit of Immunology and Infectious Diseases, Academic Department Pediatrics, Children’s Hospital Bambino Gesù, Piazza Sant’Onofrio,
of Pediatrics, Children’s Hospital Bambino Gesù, Rome, Italy 4-00165, Rome, Italy (e-mail: krzy@opbg.net).

J Pediatr Infect Dis

Abstract Brain abscesses in infants and children might be life threatening if not managed
properly. They occur more frequently in the first two decades of life despite the reduced
incidence of sinus and ear infections in pediatrics. The features of brain abscess in terms
of location, pathogens, and symptoms depend on age and thus on predisposing
factors. In infants and toddlers, bacterial meningitis or bacteremia is the major cause,
and in older children, immunosuppression and cyanotic congenital heart diseases are
common predisposing factors. The therapeutic management of brain abscesses
involves a multidisciplinary team, including infectious disease specialist, neurosurgery,
Keywords neuroradiology, and neurology. A prompt and long-term antimicrobial therapy is the
► brain abscess mainstay of treatment, often associated with surgical drainage. These changes in the
► children management have significantly improved the prognosis of patients with brain
► management abscesses over the past 50 years.

Introduction
Intracranial infections in children are rare but severe condi-
tions. Brain abscesses are focal infections that develop within
the cerebral parenchyma, usually as a complication of menin-
gitis, otitis media, mastoiditis, sinusitis, dental infections,
bacterial endocarditis, and congenital heart defects. Because
of the potential for rapid clinical deterioration and fatal out-
come, a rapid diagnosis and early treatment are necessary.
Epidemiology, Etiology, and Risk Factors
Brain abscesses occur more frequently in the first two decades
of life, but the incidence has decreased overtime with a more
appropriate treatment of sinus and ear infections in pediatrics.1
Recent studies report an incidence in patients under 15 years of
age varying between 15 and 30%.2 However, it appears to be a
clear difference between infants and children/young adults in
Both authors contributed equally to this work.
!
the main predisposing factors. Indeed, infants and toddlers are
more susceptible than other age groups to brain abscesses as
complications of bacterial meningitis or bacteremia.3 In older
children, immunosuppression and cyanotic congenital heart
diseases are common predisposing factors.4 Moreover, over
half of brain abscesses may result from sinusitis, otitis, or dental
infections. In these cases, location of abscess is closely related to
the source of infection: frontal or ethmoidal sinusitis can evolve
in frontal lobe abscesses, sphenoid sinusitis leads to temporal
lobe or pituitary gland abscesses, and otitis causes temporal
lobe or cerebellar abscesses. About 25% of cases arise from
hematogenous spread, and bacterial endocarditis or chronic
pulmonary infections (pneumonia, empyema and abscess) are
the most common sources. These abscesses are generally
multifocal and localized in the distribution area of the middle
cerebral artery. Finally, trauma, especially penetrating injury
that implants a foreign body and neurosurgery, can be com-
plicated by abscess formation1 (►Table 1).
Bacterial pathogens causing brain abscesses vary according
to the location of the primary infection, age, and underlying

received Issue Theme Central Nervous Copyright © by Georg Thieme Verlag KG, DOI https://doi.org/
December 29, 2016 System Infection; Guest Editor, Stuttgart · New York 10.1055/s-0037-1615786.
accepted after revision Elena Bozzola, MD ISSN 1305-7707.
November 5, 2017
Brain Abscesses in Children Krzysztofiak et al.

Table 1 Clinical and etiopathogenetic findings of pediatric brain abscesses

Site Temporal lobe Frontal lobe Parietal lobe Cerebellum Brain stem
Symptoms Wernicke’s aphasia/ Drowsy Impaired position Ataxia Facial weakness and
dysphasia Inattentive sense Nystagmus dysphagia
Visual field deficit Disturbed Two-point (coarser on gaze Multiple other
Mild contralateral judgment discrimination toward the lesion) cranial nerve palsies
facial Mutism Stereognosis Ipsilateral Contralateral
muscle weakness Seizures Focal sensory and incoordination of hemiparesis
Presence of motor seizures arm and leg
grasp, suck, Homonymous movements with
and snout reflexes hemianopsia intention tremor
Contralateral Impaired
hemiparesis opticokinetic
(when the abscess nystagmus
is large)
Primary Sphenoid sinusitis Frontal or Not specific Otitis Not specific
focus Otitis ethmoidal sinusitis
Etiology Streptococcus Streptococcus Not specific Streptococcus Not specific
Peptostreptococcus Peptostreptococcus Peptostreptococcus
Bacteroides Bacteroides species Bacteroides
Enterobacteriaceae Haemophilus Enterobacteriaceae
Pseudomonas species Pseudomonas
aeruginosa Fusobacterium aeruginosa
species

medical condition. By available techniques, pathogen isolation
is possible in approximately two-thirds of patients regardless
of the duration of prior antimicrobial treatment and a single
pathogen is isolated in most cases.1 Overall the most common
organisms are gram positive, particularly streptococci. Strep-
tococcus, Peptostreptococcus, and Bacteroides are usually iden-
tified in patients with contiguous spread from sinusitis and
otitis. In patients with endocarditis or cardiac disease, the most
frequent organisms are viridans streptococci, microaerophilic
species, and Staphylococcus aureus. Aerobic gram-positive
cocci and aerobic gram-negative rods are found in patients
with prior neurosurgical procedures or open head trauma.
Finally, in neonates Citrobacter and Proteus are commonly
seen.1 Severe immunosuppression is often associated with
Enterobacteriaceae, Pseudomonas, Mycobacterium, and non-
bacterial causes of infection such as fungi or parasites. HIV
infection can be complicated by brain abscesses caused by
Toxoplasma gondii, but it also predisposes patients to infection
with Mycobacterium tuberculosis.5 Patients who have received
solid-organ transplants are at risk of fungal brain abscesses
(e.g., Aspergillus or Candida species) and nocardial intracranial
infections.5
nous layers (late capsule formation > 14 days). To limit the
spread of infection, the immune response extends beyond the
capsule causing inflammation and edema in the surrounding
normal brain tissue.
Clinical Symptoms
The signs and symptoms in children with brain abscesses
depend on the location and size of the damaged area, exten-
sion of the surrounding edema, virulence, and systemic
diffusion of the pathogen.3 Neonates frequently present
with signs of systemic infection and increased intracranial
pressure, as seizures, bulging fontanel, and enlarged head
circumference.3 In older children, headache is the most
frequent symptom (50%),4 but fever, altered mental status,
nausea, vomiting, and photophobia can also appear. Thirty
to 50% of patients present with seizures.2 Focal neurological
signs are not frequent and vary with abscess location and
deleterious effect on the adjacent eloquent cortex3 (►Table 1).
The presence of papilledema can be noted on physical exam-
ination. In addition, abscess can result in rupture into the
ventricular system causing acute decompensation and symp-
toms of meningitis.6

Pathogenesis
The development of brain abscesses occurs in several stages. In
the first stage, the necrotic center is surrounded by a perivas-
cular inflammatory response with edema of the white matter
(early cerebritis, 1–4 days). Then, the necrotic center increases
in size (late cerebritis, 4–10 days); the peripheral accumula-
tion of fibroblasts and neovascularization forms a surrounding
capsule (early capsule formation, 11–14 days), which tends to
thicken in the following days through the addition of collage-
Diagnostics
Neuroimaging should be performed in all patients with
suspected brain abscess. Computer tomography (CT) scan-
ning with contrast enhancement allows a rapid detection of
size, number, and localization of abscesses. To date, magnetic
resonance imaging (MRI) is the study of choice. Diffusion-
weighted magnetic resonance imaging (DWI) is able to
differentiate ring-enhancing lesions due to brain abscesses

Journal of Pediatric Infectious Diseases


from neoplastic lesions. In the neonatal age, if MRI cannot be
obtained, bedside cranial ultrasonography represents an
alternative.6 The patient history and physical examination
can help in the identification of the predisposing factors and
the source of infection. The case assessment must guide
additional studies, which should include examination of
the teeth, echocardiogram, sinus, and middle ear imaging.
Blood and cerebrospinal fluid (CSF) cultures are infrequently
positive.7 When lumbar puncture is performed, CSF analysis
may reveal mild mononuclear pleocytosis, slight elevation
of proteins, and a normal concentration of glucose. How-
ever, the CSF culture tends to be sterile unless the abscess
has ruptured into the ventricular system. Neurosurgery is
imperative for the identification of the causative pathogen, if
it has not been determined. PCR-based 16S ribosomal DNA
sequencing on the drained purulent material may be helpful
to identify a definitive etiologic diagnosis.5
Treatment
The therapeutic management of brain abscesses involves a
multidisciplinary team, including infectious disease specia-
list, neurosurgery, neuroradiology, and neurology. A prompt
and long-term antimicrobial therapy is the mainstay of
treatment, often associated with surgical drainage. The
choice of initial antimicrobial therapy should be empirical
and based on the organisms that are the most likely cause of
the disease, considering the potential mechanism of infec-
tion and the patient predisposing factors, on local antimi-
crobial susceptibility, and on the ability of the antimicrobial
agent to penetrate the abscess capsule.5 A combined therapy
with a third- or fourth-generation cephalosporin and metro-
nidazole should be the regimen of choice for patients with a
brain abscess arising from an oral, otogenic, or sinus source.
Considering that the isolation of anaerobic bacteria from
cultures is very hard because of their slow growth, anaerobic
coverage is often maintained even if the organism is not
identified,6 especially if the infection is from a contiguous
site.5 In patients with contraindications to therapy with
cephalosporin or metronidazole, meropenem may be con-
sidered as an alternative empirical treatment. When
S. aureus is suspected, that is, hematogenic origin or follow-
ing neurosurgery or penetrating trauma, vancomycin or
linezolid should be added.8 In transplant patients, the addi-
tion of voriconazole and trimethoprim–sulfamethoxazole or
sulfadiazine should be considered because of the increased
risk of fungal and Nocardia infections. Patients with HIV
infection may require therapy with pyrimethamine plus
sulfadiazine for Toxoplasma coverage. Moreover, in HIV-
infected children and in patients who are immigrants from
endemic areas, treatment of tuberculosis should be consid-
ered.5 In the neonatal age, cefotaxime plus ampicillin could
be a potential empirical therapy.6
Therapy has to be narrowed when a specific organism
or multiple organisms are identified. Parenteral antibiotics
are required for 4 to 6 weeks in surgically treated abscesses,
and 6 to 8 weeks for those with medical treatment only.1 A
longer course (>6 weeks) is suggested also for necrotic and/
Brain Abscesses in Children Krzysztofiak et al.
or encapsulated abscess with tissue necrosis, multiloculated
abscess, abscesses in vital intracranial locations (i.e., brain
stem), and in immunocompromised patients. However, the
duration of antimicrobial treatment should be guided by
continuous assessment of the clinical course and follow-up
imaging studies; thus, antibiotics should be continued until a
clinical response occurs and CT or MRI findings demonstrate
a complete resolution. Because the abscess site may show
persistent enhancement for several months, this finding
alone is not an indication to continue antimicrobial therapy
or for surgical drainage. A conservative approach based on
medical treatment alone can be considered in abscesses
smaller than 2.5 cm in diameter, multiple small abscesses,
or for patients who are extremely poor surgical candidates.1
Usually, along with medical treatment, most brain abscesses
need surgical drainage1 that are often performed using
frameless stereotactic bur hole aspiration. In a cohort from
the Virginia Children’s Hospital as well as in the Children’s
Hospital Boston study, majority of children only required a
single aspiration.6 Excision is the method of choice for multi-
lobulated, superficial, or posterior fossa abscesses, those that
contain a foreign body, and those nonresponding to previous
needle aspiration.1,6
Outcome
The outcome for patients with brain abscess has improved over
the past 50 years, following improvements in cranial imaging
techniques, the use of more appropriate antimicrobial treat-
ment regimens, and the introduction of minimally invasive
neurosurgical procedures.7 Current mortality rate has been
reported in the 4 to 10% range.7,9,10 Poor prognosis is asso-
ciated with delayed diagnosis, immunocompromised states,
intraventricular rupture of the abscess, fungal etiology, and
pretreatment neurologic state of the patient. Factors, such as
male gender and gram-positive cocci infection, have been
associated with favorable outcome in some reports.1
Conclusion
Brain abscesses in children are serious and life-threatening
conditions that need early and appropriate treatment. The
identification of the primary source of the infection is impor-
tant to guide the empirical choice of antibiotics. Successful
treatment requires a multidisciplinary approach, including
diagnostic imaging, antibiotic administration, and surgical
drainage. Newer antibiotics, better microbiological tests, and
progress in surgical techniques will be needed to further
decrease mortality and improve outcomes.
References
1 Frazier JL, Ahn ES, Jallo GI. Management of brain abscesses in children.
Neurosurg Focus 2008;24(06):E8. doi: 10.3171/FOC/2008/24/6/E8
2 Bonfield CM, Sharma J, Dobson S. Pediatric intracranial abscesses.
J Infect 2015;71(Suppl 1):S42–S46
3 Muzumdar D, Jhawar S, Goel A. Brain abscess: an overview. Int J
Surg 2011;9(02):136–144
Journal of Pediatric Infectious Diseases
 Brain Abscesses in Children Krzysztofiak et al.
4 Goodkin HP, Harper MB, Pomeroy SL. Intracerebral abscess in
children: historical trends at Children’s Hospital Boston. Pediatrics
2004;113(06):1765–1770
5 Brouwer MC, Tunkel AR, van de Beek D. Brain abscess. N Engl J Med
2014;371(18):1758
6 Brouwer MC, Coutinho JM, van de Beek D. Clinical characteristics
and outcome of brain abscess: systematic review and meta-
analysis. Neurology 2014;82(09):806–813
7 Sheehan JP, Jane JA, Ray DK, Goodkin HP. Brain abscess in children.
Neurosurg Focus 2008;24(06):E6. doi: 10.3171/FOC/2008/24/6/E6
Journal of Pediatric Infectious Diseases
View publication stats
8 Krzysztofiak A, Bozzola E, Lancella L, Quondamcarlo A, Gesualdo F,
Ugazio AG. Linezolid therapy of brain abscess. Pediatr Infect Dis J
2010;29(11):1063–1064
9 Shachor-Meyouhas Y, Bar-Joseph G, Guilburd JN, Lorber A, Hadash
A, Kassis I. Brain abscess in children - epidemiology, predisposing
factors and management in the modern medicine era. Acta
Paediatr 2010;99(08):1163–1167
10 Felsenstein S, Williams B, Shingadia D, et al. Clinical and micro-
biologic features guiding treatment recommendations for brain
abscesses in children. Pediatr Infect Dis J 2013;32(02):129–135