Brain abscess and it course of treatment

Overview of Brain Abscess

1. Dr. Joe M Das
Senior Resident
Dept. of Neurosurgery
Brain abscess

2. History
Definition
Epidemiology
Pathogenesis
Clinical features
Investigations
Treatment
Special abscesses

3. History
Hippocrates –Purulent otorrheaand delerium
The first successful operation for brain abscess -S.F. Morand
(France) in 1752 on a temperoethmoidalabscess.
“PyogenicDisease of the Brain and Spinal Cord, Meningitis,
Abscess of the Brain, Infective Sinus Thrombosis” (1893) -
William Macewen–Father of modern day abscess management
King (1924) –marsupialization
Dandy (1926) –aspiration
Sargent(1928) –enucleation
Vincent (1936) –complete excision
Heinemanet al (1971) –successful medical management

4. Henry II, King of France
Death was predicted by
Nostradamus
Died from an orbital wound
The skull was not penetrated
but infection spread
intracranially
Infection had spread to the
brain along the orbital veins,
forming an abscess under the
cortex.

5. Oscar Wilde
Irish writer and poet
Died of otogenicbrain
abscess

6. Definition
MathisenGE, Johnson JP: Brain abscess. ClinInfect Dis
1997; 25:763-781.
A focal intracranial
infection that is initiated as
an area of cerebritisand
evolves into a collection of
pus surrounded by a
vascularizedcapsule.

7. Epidemiology
1500-2500 cases per year in the US
8% of ICSOL in developing countries
♂: ♀= 2-3 : 1
Median age –30 –40 yrs
2°to otiticfocus -<20 / > 40 yrs
2°to PNS infection –30-40 yrs
25% in children –otiticfocus / CHD
0.2% of cranial operations
Immunosuppression

8. Pathogenesis
Sources:
Contiguous source –25-50 %
Hematogenousdissemination / trauma –20-35 %
Cryptogenic –10-35 %

9. Contiguous spread
Routes of contiguous spread:
Direct extension through osteitis/ osteomyelitis
Retrograde thrombophlebitisvia diploicor emissary vein
Via local lymphatics
Localisation:
Otitismedia –Temporal lobe / cerebellum
PNS –Frontal lobe
Sphenoid sinusitis –Temporal lobe / sella
Dental infection (molars) –Frontal lobe (M.C) / temporal

10. India –M.C source –
Middle ear suppuration
Western countries –M.C
source –Spread from PNS
Sites of bone dehiscence:
Post wall of frontal sinus
Tegmentympani
Trautmann’striangle

11. Hematogenous
Multiple, multiloculatedabscesses -↑mortality
M.C sources in adults –chronic pyogeniclung diseases (especially
lung abscess), bronchiectasis, empyema, and CF.
Distant sources –wound & skin infections, osteomyelitis, pelvic
intra-abdominal infections; after esophageal dilation or sclerosing
therapy for esophageal varices.
CCHD (TOF/ TGV) –5-15% of brain abscess cases.
<5% of patients with IE despite the presence of continuous
bacteremia
Hereditary hemorrhagic telangiectasia(with coexisting pulmonary
AVM) -allows septic emboli to cross the pulmonary circulation
without capillary filtration –5-9% risk

12. How does TOF lead to brain abscess?
TOF Chronic hypoxemia Polycythemia
↑viscosity Multiple infarcts at grey-white
junction Milieu for bacterial growth

13. Trauma
Open cranial fracture with duralbreach / foreign body
injury / as a sequel of neurosurgery
Civilian population -2.5-10.9 %
Includes those 2°to compound depressed skull
fractures, dog bites, rooster pecking, tongue piercing
Nosocomialbrain abscess -halo pin insertion, electrode
insertion to localize seizure foci, and in malignant glioma
patients treated by placement of Gliadelwafers

14. In military populations -3-17 %
Usually occur secondary to retained bone fragments or
contamination of initially uninfected missile sites with
bacteria from skin, clothes, or the environment
The retained foreign bodies did not seem to increase the
infection rate except in patients who suffered an in-
driven cluster of bone fragments or leakage of
cerebrospinal fluid.

15. Predisposing Conditions and Probable
Etiologic Agents in Brain Abscess

16. Predisposing Conditions and Empirical
Antimicrobial Therapy in Patients with
Presumed Bacterial Brain Abscess

17. Antimicrobial Therapy for Brain
Abscess Based on Isolated Pathogen

19. Recommended Dosages of Antimicrobial
Agents in Adults with Brain Abscess and
Normal Renal and Hepatic Function

20. Stages of abscess formation
A canine model after inoculation of α-hemolytic Streptococci
Britt RH, Enzmann DR, Yeager AS. Neuropathological and computerized tomographicfindings
in experimental brain abscess. J Neurosurg. 1981 Oct;55(4):590-603.

21. Stages of abscess formation

24. Histopathologicfindings in the stages
of brain abscess formation
Data from TunkelAR, ScheldWM. Pathogenesis and pathophysiologyof bacterial infections. In: ScheldWM, Whitley RJ, Durack, DT, eds. Infections of the Central
Nervous System, tinded. Philadelphia: Lippincott-Raven; 1997;297-312; and Britt RH, EnzmannDR, Yeager AS. Neuropathologicaland computerized tomographicfindings in
experimental brain abscess. J Neurosurg. 1981;55:590-603.

25. Early cerebritis
Acute inflammatory
infiltrate
Marked edema
Invisible on CT OR
Poorly marginatedcortical
/subcorticalhypodensity
with mass effect with no
enhancement

26. Late cerebritis
Central necrosis
Macrophages and
fibroblasts
Vascular proliferation
Maximum edema
Irregular rim enhancing
lesion with
hypodensecenter, better
defined than early
cerebritis

27. Early capsule formation
Necrotic centre ↓
Collagenouscapsule
Edema starts to regress
Well-defined rim
enhancing mass; an outer
hypodenseand inner
hyperdenserim (double
rim sign)

28. Late capsule formation
Collagen capsule complete
↑density and thickness
Rim enhancing lesion with
thickened capsule and
diminished hypodense
central cavity

29. Layers of abscess

30. Immunopathogenesis

31. Why does abscess often rupture
intraventricularly?
Difference in vascularitybetween cortical grey
and white matter 
↑fibroblast proliferation on cortical side 
Capsule less formed on ventricular surface 
Tendency for intraventricularrupture

32. Initial Symptoms and Signs in Patients
with Brain Abscess

33. Initial Findings in Patients with Brain
Abscess Based on Intracranial Location
Frontal > Temporal >
Parietal > Cerebellum >
Occipital

34. Classic triad of headache, fever, and focal neurologic
deficit is rarely seen (< 5-20% of cases in case series)
1/3
rd
–polymicrobial
Incidence of negative cultures -25-30%
Sudden worsening of a preexisting headache
accompanied with meningismusmay be indicative of a
catastrophic event—rupture of the abscess into the
ventricular space.

35. When there is no obvious source (up to 25% of cases),
upper respiratory tract flora and anaerobes are often
isolated.
Several sources have identified a patent foramen ovaleby
echocardiogram in these cases and propose this as a
possible mechanism for seeding oral flora to the brain.
KhouzamRN, El-DoklaAM, MenkesDL. Undiagnosed patent foramen ovale
presenting as a cryptogenic brain abscess: case report and review of the literature.Heart
Lung. Mar-Apr 2006;35(2):108-11.

36. Investigations
X-ray skull:
Often normal
Post-traumatic –air inside cranial cavity
Sinusitis/mastoiditis
CT brain:
Diagnosis, localisationand treatment
Sinisitis/mastoiditis
Staging, HCP, ↑ICP, edema, associated subdural empyema,
meningitis, ventriculitis, multiplicity
NCCT -Isodense/ hyperdense
CECT -Smooth, thin, regular wall with decreased density both
in the centre and surrounding

37. MRI Brain
T1
Central low intensity (hyperintenseto CSF)
Peripheral low intensity (vasogenicoedema)
Ring enhancement
Ventriculitismay be present, in which case hydrocephalus will commonly
also be seen
T2 / FLAIR
Central high intensity (hypointenseto CSF, does not attenuate on FLAIR)
Peripheral high intensity (vasogenicoedema)
The abscess capsule may be visible as a intermediate to slightly low signal
thin rim
DWI/ ADC
High DWI signal is usually present centrally
Low signal on ADC

38. SWI
Low intensity rim
Complete in 75%
Smooth in 90%
Mostly overlaps with contrast enhancing rim
Dual rim sign-a hyperintenseline located inside the low intensity
rim
MR perfusion-RCBV is reduced in the surrounding oedema
c.f. to both normal white matter and tumouroedemaseen in high
grade gliomas
MR spectroscopy-elevation of a succinatepeak is relatively
specific but not present in all abscesses ;high lactate,
acetate,alanine, valine, leucine, and isoleucinelevels peak may be
present ; cho/ crnand NAA peaks are reduced

44. What are the imaging differential
diagnoses?

45. How to differentiate between peripherally
enhancing neoplasm and abscess radiologically?

47. Laboratory investigations
TC –Normal / mild ↑(↑if meningitis / acute systemic infection)
ESR -↑in >90%
CRP -↑. Useful marker to differentiate between brain abscess and
slowly progressive ICSOLs
Blood culture -+vein IE / mycoticaneurysms
CSF analysis –Non-specific.
Mild pleocytosis. CSF potein–mild ↑
Glu–Normal
LP –dangerous
PCR analysis of 16S rDNA–to identify to species level

111
In-labelled leukocytes

48. Treatment

49. Surgical therapy
The optimal approach to patients with bacterial brain abscess
Aspiration after bur-hole placement or complete excision after
craniotomy (no prospective trial comparing these two)
May be performed under stereotactic neuroimagingguidance
Stereotactic aspiration is a useful approach even for abscesses
located in eloquent or inaccessible regions; repeat aspiration
should be considered if the initial aspiration proves ineffective or
partially effective.
Intraoperativeultrasound -for the aspiration of small abscesses
and can delineate abscess pockets,
Recurrence rates after stereotactic aspiration range from 0-24 %.

50. Pus has been aspirated. What all
investigations are to be sent?
A.Stains
A.Gram stain
B.Acid-fast stain (AFB stain) for Mycobacterium
C.Modified acid-fast stain (for Nocardia) looking for branching acid
fast bacillus
D.Special fungal stains (e.g., methenamine silver, mucicarmine)
B.Cultures
A.Routine cultures: aerobic and anaerobic
B.Fungal culture: this is not only helpful for identifying fungal
infections, but since these cultures are kept for longer period and
any growth that occurs will be further characterized, fastidious or
indolent bacterial organisms may sometimes be identified
C.TB culture

51. What are the indications for initial
surgical treatment?
1.Significant mass effect exerted by lesion (on CT or MRI)
2.Difficulty in diagnosis (especially in adults)
3.Proximity to ventricle: indicates likelihood of intraventricular
rupture which is associated with poor outcome
4.Evidence of significantly increased intracranial pressure
5.Poor neurologic condition (patients responds only to pain, or
does not even response to pain)
6.Traumatic abscess associated with foreign material
7.Fungal abscess
8.Multiloculatedabscess
9.Follow-up CT/MRI scans cannot be obtained every 1-2 weeks

52. What are the indications for complete
excision by craniotomy ?
Multiloculatedabscesses in whom aspiration techniques have failed
Abscesses containing gas
Abscesses that fail to resolve
Posttraumatic abscesses that contain foreign bodies or retained
bone fragments to prevent recurrence
Abscesses that result from fistulous communications (e.g.,
secondary to trauma or congenital dermal sinuses)
Abscess localized to one lobe of the brain and contiguous with a
primary focus.
Cerebellarabscess in children
Difficulty in diagnosis
Suspected fungal abscess

53. What are the contraindications for
craniotomy and evacuation?
Abscess in the cerebritisstage
Deep-seated abscess in eloquent area
Multiple abscesses

54. Aspiration vs. Craniotomy
Craniotomy is now rarely practiced as the first line of treatment.
Aspiration repeated as necessary or with drainage, has widely replaced
attempts at complete excision.
Several reports have advocated excision as the procedure of choice
because it is often followed by a lower incidence of recurrence and
shorter hospitalization.
Xiao et al reported that favorable outcome was not significantly different
between the patients treated by excision or aspiration. However, the
mortality rate was significantly lower in the patients treated with
excision than the patients treated with aspiration.
This is probably due to the better general condition and/or more
favorable location of abscess that could be excised surgically in such
patients.
Stereotactic aspiration should be considered the treatment of choice in
all but the most superficial and the largest cerebral abscesses.

55. IV rupture with ventriculitis and HCP –
What to do?
Rapid evacuation and débridement of the abscess cavity via
urgent craniotomy
+
Ventricular drainage
+
Intravenous or intrathecal administration of appropriate
antimicrobial agents

56. When to opt for medical therapy alone?
Patients with medical conditions that increase the risk
associated with surgery
Multiple abscesses
Abscesses in a deep or dominant location
Coexisting meningitis or ependymitis
Early reduction of the abscess with clinical improvement
after antimicrobial therapy
Abscess size < 3 cm

57. What is the optimal duration of
medical treatment?
Bacterial brain abscess –6-8 weeks IV →2-3 months oral
antimicrobial therapy
Post-surgical excision -Courses of 3 to 4 weeks of antimicrobial
therapy
Medical therapy alone -up to 12 weeks with parenteralagents
A combination of surgical aspiration or removal of all abscesses
larger than 2.5 cm in diameter →6 weeks or more of
antimicrobial therapy, and weekly neuroimagingto document
abscess resolution
Repeat neuroimagingstudies -biweekly for up to 3 months after
completion of therapy

58. How will you follow up an abscess case
radiographically?
CT scans weekly during the course of therapy 
One week after discontinuation of antibiotics 
Scan one month later 
Monthly or bimonthly till radiographic resolution
Time course for abscess resolution:
↓in abscess size –2-3 weeks after initiating therapy
Complete resolution of abscess cavity, mass effect –3-4 months
Residual contrast enhancement –6-9 months

59. Brain abscess –
Management algorithm

60. Any role for steroids?
↓host defense mechanisms and ↓penetration of some antimicrobial
agents into the brain abscess cavity
May result in improvement of neurological symptoms and signs.
Therapy started in abscess patients with:
Associated edema and mass effect
Progressive neurological deterioration
Impending cerebral herniation.
Dose:
Dexamethasone, 10 mg every 6 hours is generally administered initially
and then tapered once the patient has stabilized.
The use of prolonged courses of corticosteroids is discouraged.
May also decrease contrast enhancement of the abscess capsule in the
early stages of infection, thereby being a false indicator of radiologic
improvement.

61. What is the role of anticonvulsants?
Initiated immediately and continued at least 1 year due to
high risk in the brain abscesses.
The treatment can be discontinued if no significant
epileptogenicactivity can be shown in electroencephalogram
(EEG).

62. How to treat otogenic brain abscess?
Initial neurosurgical removal of abscess, which after
improvement of general condition of the patient should
be followed by radical otosurgicalremoval of the process
from the ear.
Otogenicbrain abscess: diagnostic and treatment experience. D DjericN ArsovicV
Djukic. International Congress Series, 2003; 1240 (61-65)
Brain abscesses of otogenicorigin. [Article in Serbian] NesićV1, JanosevićL, StojicićG,
JanosevićL, BabacS, SladojeR. SrpArhCelokLek. 2002 Nov-Dec;130(11-12):389-93.

63. How to manage multiple brain
abscesses?
Incidence –10-50%
Emergent stereotactic aspiration for all lesions > 2.5 cm diameter and
those causing mass effect, located deep in brain stem or close to
ventricular wall
If all the lesions are < 2.5 cm and not producing mass effect, the
largest one should be aspirated for diagnostic cultures.
Antibiotics withheld till culture results
Antibiotics for 3 months (Immunosuppressed–1 yr)
Repeat surgical aspiration if
radiographic enlargement after 2 weeks of therapy
Failure to diminish in size after 4 weeks of antibiotics
Clinical deterioration

64. How to treat Nocardial brain abscess?
A sulfonamide ±trimethoprim, is recommended.
Alternative agents include minocycline, imipenem, amikacin, third-
generation cephalosporins, and linezolid
In immunocompromisedpatients or those in whom therapy fails
a third-generation cephalosporin or imipenem+ a sulfonamide or
amikacin
Nocardiafarcinica, a species that may be highly resistant to various
antimicrobial agents, successful treatment has included
moxifloxacin.
Craniotomy with total excision is difficult in patients with Nocardia
brain abscess because these abscesses are often multiloculated.
The duration of therapy -3 to 12 months, but it should probably
be continued up to 1 year in those who are immunocompromised.

65. What are the treatment options for
fungal brain abscess?
Patients with fungal brain abscess, especially those who are
immunocompromised, have a high mortality rate despite
combined medical and surgical therapy.
Candidalbrain abscess -AmphotericinB preparation + 5-
flucytosine
The therapy of choice for Aspergillusbrain abscess is voriconazole.
Alternative agents include an amphotericinB preparation,
posaconazole, and itraconazole.
Itraconazole-as an extension of successful treatment rather than
as primary therapy.
Excisionalsurgery or drainage is a key factor in the successful
management of CNS aspergillosis.

66. CNS mucormycosis-AmphotericinB deoxycholateor a lipid
formulation of amphotericin
Correction of the underlying metabolic derangements and
aggressive surgical débridement
The etiologic agents of mucormycosisinvade blood vessels,
tissue infarction occurs and impairs the delivery of antifungal
agents to the site of infection; this often leaves surgery as the
only modality that may effectively eliminate the infecting
microorganism.
In patients not responding to or intolerant of an
amphotericinB formulation, posaconazolecan be used as
salvage therapy.
HBO -useful adjunct
Surgery is the cornerstone of therapy for brain abscesses
caused by Scedosporiumspecies
Voriconazoleis the agent of choice.

67. What is meant by delayed “glue
abscess”?
Delayed multiloculatedabscess after embolizationof AVM
nidus
The duration of the procedure and repeated handling of the
catheters along with use of large amount foreign material or
Hysto-acryl “glue” can precipitate infection.
Cure of the lesion can only be obtained by surgical excision
of the infected and partially embolizedAVM.
Antibiotic prophylaxis with all endovascular procedures is
recommended
MourierL, BellecC, Lot G, ReizineD, GelbertF, DematonsC, et al. Pyogenicparenchymatousand nidusinfection after embolization
of an arteriovenousmalformation: an unusual complication. Case report. ActaNeurochir(Wien) 1993;122:130-3.
PendarkarH, KrishnamoorthyT, PurkayasthaS, Gupta AK. Pyogeniccerebral abscess with discharging sinus complicating an
embolizedarteriovenousmalformation. J Neuroradiol2006;33:133-8

68. What are the factors to be considered in a patient
with cyanotic heart disease developing a brain
abscess?
5-18% population with CHD. 10 times more prone. M.C –TOF
Intracardiacright to left shunt by-pass allows direct entry of blood
containing bacteria to the cerebral circulation without pulmonary
filtration.
Anaerobic streptococci (Sterile cultures are reported in 16-68%)
Cardiopulmonary risk, coagulation defects and variable degree of
immunodeficientstates
A deeply located parieto-occipital abscess larger than 2 cm
diameter which causes mass effect, should be aspirated
immediately even in late cerebrititsstage using stereotactic or CT
guided methods to decrease intra-cranial pressure and avoid
intraventricularrupture of brain abscess.
Intravenous Beta-lactamantibiotics are started immediately.

69. Cerebellarabscess
6-35% of all brain abscesses
Often ominously silent and carry significant mortality
Can cause sudden total occlusion of CSF pathways early in
the course of disease.
Presence of periventricularlucencyis an absolute indication
of immediate ventricular drainage regardless of level of
consciousness i.e. even if patient is fully conscious.
Burr hole aspiration has emerged as a satisfactory method

70. Sequelae
30-50% of survivors are found to have neurological sequelae.
The incidence of residual neural deficits -hemiparesis,
cognitive and learning deficits in children, is less with
aspiration than excision.
About 72% of patients can have epileptic seizures uptofive
years of diagnosis. This incidence is less with aspiration than
excision.
5 to 10% abscesses recur due to inadequate or inappropriate
antibiotics, failure of removal of foreign body, duralfistula or
failure of eradication of primary source.
Hydrocephalus may also develop

71. What is the difference between otogenicand odontogenic
brain abscess?
Unlike otogenicabscess, odontogenicabscess occurs as a
sequel of acute rather than chronic infection
What is the most common site of metastatic abscess?
In the distribution of MCA –Parietal & frontal (left side)
Grey-white junction –capillary flow slowest
Does a high velocity bullet injury cause an abscess?
The fragments do not present a significant risk because of
heat sterilisationand do not require removal