Definition
- Focal intracranial infection that starts as a focus of cerebritis that gradually progresses into a collection of pus with capsular formation
Numbers
- 1% of all SOL
- Men: woman 1:3
- Incidence of 0.4/100.000/year (Helweg- Larsen et al., 2012) in developed world and higher in developing countries
Risk factor
- Immunosuppressed
- HIV positive
- AIDS
- Immunosuppressive treatment
- Chemotherapy for treatment of malignancy,
- Steroids,
- Pulmonary AVF: (Helweg- Larsen et al., 2012; Chenran et al., 2014; Yakut et al., 2015)
- Osler Weber Rendu syndrome: 36-40 YM
- 5% patients develop cerebral abscess
- Due to shunting from lung AVMs
Pathogenesis
Haematogenous spread from distant sites (Most common)
- Adults
- Bacterial endocarditis rarely give rise to brain abscess
- Subacute bacterial endocarditis mainly cause embolic stroke rather than abscesses
- Acute bacterial endocarditis due to staphylococcus or haemolytic streptococcus → associated with multiple abscesses
- 5% patient develop cerebral abscesses
- Lung abscesses/infections/empyema/CF
- Skin/bone/GI infections
- GI infection: may give rise to brain via Batson plexus
- Children
- Congenital cyanotic heart disease
- Eg: tetralogy of Fallot and transposition of the great vessels
- Inc. %Hb + hypoxic environment + losing lung filtration → Ischaemic brain increases septic embolization spread
- 5% to 15% cases of all brain abscess cases
- Causes multiple abscesses
Contiguous spread from adjacent sites
- Purulent sinusitis
- Local osteomyelitis + phlebitis of emissary vein → cerebral abscess
- Don’t get it for infants because they don't have well aerated mastoid and paranasal air cells
- Location
- Middle ear and mastoid air sinusitis → temporal lobe and cerebellar abscess
- Ethmoidal and frontal sinusitis → frontal lobe abscess
- Sphenoid sinusitis → cavernous sinus (danger) temporal lobe
- Odontogenic
- Frontal lobe
- Dental procedure past 4 weeks
Direct inoculation
- Penetrating trauma
- Worse when it travels through air sinuses
- Gunshot wound abscess is low with prophylactic antibiotics
- Arise from bacteria from skin/clothes/enviroment
- NS(x) post op
- Post craniotomies
- EVD, ICP monitor, Halo traction
- Electrode insertion
Pathogens
Fq (Helweg- Larsen et al., 2012; )
- Streptococci 54%
- Staphylococci 15%
- Gram- negative bacteria 8%
- Anaerobic bacteria 17%
- Nocardia 2%
- Incidence of negative culture can be as high as 43%
- Might be due to use of antibiotic prior to sampling
Frontal and ethmoidal sinusitis
- Most common
- Strep. Milleri
- Strep. Anginosus
Post traumatic
- Staph Aureus
- Staph enterobacteriae
- Clostridium spp.
Lung infections
- Fusobacterium
- Actinomyces
- Bacteroides spp
- Prevotella spp
- Streptococci;
- Nocardia spp
Dental
- Mixed Fusobacterium,
- Prevotella,
- Actinomyces,
- Bacteroides spp
- Streptococci
Post NS(x) op
- Staph. Epidermidis
- Staph. Aureus
Congenital heart disease
- Streptococci,
- Haemophilus spp
Immunocompromised
- Mycobacterium (Mohindra et al., 2016)
- Tuberculous brain abscess requires investigation to rule out underlying HIV exposure.
- Diagnostic criteria as described in 1978 by Whitener are:
- Macroscopic evidence of true abscess formation within the brain substance (at surgery or biopsy)
- Histological confirmation that inflammation in the abscess was composed predominantly of vascular granulation tissue containing acute and chronic inflammatory cells.
- Positive pus culture or evidence of acid- fast bacilli.
- Female patients tend to be more afflicted compared to males with a mean age of 23.9 years.
- Incidence of tuberculous brain abscess is 4–8% of CNS tuberculosis in the absence of HIV infection
- Investigation
- Tuberculoma mimics multiple other entities on CT/MRI
- Metastatic brain tumours,
- Neurocysticercosis,
- Toxoplasmosis
- Fungal brain abscess
- CSF evaluation in isolated tuberculoma is generally non- specific.
- Pathology
- They are firm, avascular, spherical masses that range from 2 to 10 cm in diameter, well- circumscribed, and contain areas of caseating necrosis with tubercle bacilli.
- Management
- Medical therapy main.
- Surgery (Chatterjee, 2011; Monteiro et al., 2013)
- Less used as as most tuberculoma responds well with adequate antibiotic treatment and steroids.
- Occasionally, warranted for diagnosis purposes or to relieve significant mass effect
- Toxoplasma Gondii
- Nocardia Asteroides
- Mortality from Nocardia brain abscesses 31– 77%
- Treatment: trimethoprim-sulfamethoxazole regime for a 3 to 12 months (Weerakkody et al., 2015)
- Candida albicans
- Listeria monocytogenes
- Fungal infection (Vergara et al., 2015)
- Eg:
- CNS aspergillosis,
- Aspergillus fumitagus
- Scedosporium,
- Cryptococcus neoformans
- Endemic mycoses
- High mortality rate in immunocompromised
Infants
- Gram Neg because IgM don’t cross placenta
- Citrobacter , Bacteroides , Proteus , and gram-negative bacilli
Stages of infection
- Canine model of infection after inoculation with α-hemolytic streptococci (PMID: 6168748-britt et al 1981, Erdogan and Cansever, 2008)
Early cerebritis | Late cerebritis | Early capsule formation | Late capsule formation | |
Days | 1-3 | 4-9 | 10-13 | 14 and above |
Resistance of capsule to needle aspiration | Intermediate resistance | No resistance | No resistance | Firm resistance. Has pop on entering |
Necrotic centre | Acute inflammatory cells; bacteria present on gram stain | Enlarging necrotic centre reaching maximal size | Decrease in necrotic centre | Further decrease in necrotic centre |
Inflammatory border | Acute inflammatory cells | Inflammatory cells, macrophages and fibroblast | Inc. numbers of fibroblast and macrophages | Further inc. in number of fibroblast |
Cerebritis and neovascularity | Rapid perivascular infiltration of neutrophils, plasma cells, and mononuclear cells | Maximal extent of cerebritis Rapid inc. in new vessel formation | Maximal degree of neovascularization | Cerebritis restricted to the outside of the collagen capsule Reduce neovascularity |
Collagenous capsule | Reticulin formation begins by day 3 | Appearance of fibroblast with rapid formation of reticulin | Evolution of mature collagen | Capsule completed by end of second week |
Reactive gliosis and cerebral oedema | Marked cerebral oedema | Prominent cerebral oedema Appearance of reactive astrocyte | Regression of cerebral oedema Inc. in reactive astrocyte | Regression of cerebral oedema Marked gliosis outside capsule by 3rd week |
CT | Partial ring contrast enhancement on Day l evolved to well-developed ring enhancement by Day 3 Steroids reduce degree of contrast enhancement (especially in cerebritis) | Thick Ring enhancement Diffusion of contrast medium into the lucent centre on delayed scans (30-60 min after contrast infusion) was salient CT finding of cerebritis stage | Ring enhancement with less diffusion of contrast material into lucent centre was seen in incompletely encapsulated abscesses | Ring enhancement without diffusion of contrast material into lucent centre was salient feature of well encapsulated abscess |
MRI | T1: Lesion center → low signal, capsule → mildly hyperintense, T2: Center → iso- or hyperintense, capsule → dark (collagen) DWI: Restriction because the pus is very restrictive | Perilesional (vasogenic) edema → low signal Perilesional edema → hi signal T1 contrast ring enhancing lesion |
Localization
- Gray-white matter junction
- Watershed area
- Ischaemic area
- Multiple in 21% (Helweg- Larsen et al., 2012)
- Tend to rupture into ventricles
- Due to capsule is thinner near deeper it is
- Close to the cortex, more oxygen, more fibrosis
- Frontal (37%) >temporal>parietal (27%) (Helweg- Larsen et al., 2012)
- Reduce temporal because ear infections tx better
- Frontal abscesses: contiguous spread,
- Parietal and multiple abscesses : haematogenous spread
Clinical features
- Symptoms progress faster than cancer
- <2 wks
- Adults
- Nonspecific.
- Classical triad of
- Headache +fever + nausea or vomiting: one in five cases
- Headache + fever + focal neurological deficits: one in four cases.
- Abscess → surrounding oedema → causing neurology → Hemiparesis and seizure
- Mass effect from abscess/perilesional oedema → Inc. ICP → N/V H/A Lethargy, Low GCS
- Meningismus
- Almost never present with meningismus
- Sudden worsening of the headache, accompanied by new onset of meningismus, may signify rupture of the abscess into the ventricular space.
- Intraventricular rupture appears to be more likely if the abscess is deep-seated, multiloculated, and in close proximity to the ventricular wall
- A 1-mm reduction of the distance between the ventricle and the abscess increased the rupture rate by 10%
- Severe headaches and signs of meningeal irritation were prominent findings before rupture and were followed by rapid clinical deterioration within 10 days.
- Location specific
- Fq (Helweg- Larsen et al., 2012)
- Fever (60%),
- Neck stiffness (25%)
- May be due to
- Meningitis
- Ventriculitis (rupture of abscess into ventricle)
- Nausea or vomiting (40%),
- Focal neurological deficits (57%)
- Hemiparesis, personality change, visual field deficits, aphasia, nystagmus, and ataxia.
- Seizures (21%)
- Impaired consciousness (45%)
- Neonates
- Inc. ICP → macrocranium
- Seizure, irritability
- Failure to thrive
Evaluation
- Blds
- ESR might be normal. It is even reduced in cyanotic heart disease where polycythemia reduces ESR
- CRP: raised
- LP: AVOID IT
- Dubious: CSF is abnormal in >90% there is no characteristic finding to diagnose abscess
- OP: raised
- WCC and Prot: raised
- Glucose: dec.
- Low CSF positivity: unless abscess rupture into ventricles
- Abscess culture
- Gram stain
- Acid-fast stain for Mycobacterium (AFB stain, acid-fast resist decolorization with an acid-alcohol mixture and retain the initial dye carbolfuchsin and appear red. The genus Mycobacterium and the genus Nocardia are acid-fast, all other bacteria will be decolorized and stain blue, the color of the counterstain methylene blue)
- Modified acid-fast stain (for Nocardia, see below) looking for branching acid-fast bacillus
- Special fungal stains (e.g., methenamine silver, mucicarmine)
- Culture
- Routine cultures: aerobic and anaerobic
- Fungal culture
- This is not only helpful for identifying fungal infections, but since these cultures are kept for longer periods and any growth that occurs will be further characterized, fastidious or indolent bacterial organisms may sometimes be identified
- TB culture
- Molecular testing: PCR (mycobacteria, EBV, JC virus)
- CT
- CT+C
- Ring enhancing
- MRI
- Diagnostic neuroimaging of choice
- Better than CT
- More sensitive
- Can detect early cerebritis
- More conspicuous demonstration of spread of inflammation into the ventricles and subarachnoid space
- Earlier detection of satellite lesions
- ADC mapping
- T1
- Rim is isointense to mildly hyperintense
- Central low intensity (hyperintense to CSF)
- Peripheral low intensity (vasogenic oedema)
- T2/FLAIR
- Rim is low intensity
- Peripheral High intensity (vasogenic oedema)
- T1+C
- Ring- enhancing lesion
- In immunocompromised patients, there may be relative lack of contrast enhancement which can confound diagnosis.
- Tuberculous and fungal cerebritis
- Tuberculous cerebritis is seen as an ill- defined, hypoattenuated areas of gyral enhancement.
- Fungal
- Fungal cerebritis is usually nonenhancing and located in the basal ganglia or deep white matter
- Half of fungal abscess have a creanated wall
- Show intracavitary projections directed centrally from the wall without any contrast enhancement, this is not seen in other type of abscess on conventional MRI
- All mature pyogenic, tubercular, and fungal abscesses demonstrate hypointensity on T1 imaging, hyperintensity on T2 imaging, and demonstrate good rim enhancement on contrast sequences
- Pyogenic and tubercular abscesses show a smooth or lobulated outer- wall.
- DWI + ADC
- Tuberculous and pyogenic abscess
- Increase signal in DWI + low apparent ADC values within the core of the cavity
- Necrotic material is present within the abscess cavity which contains inflammatory cells, bacteria, and pus which restricts water- motion
- Use of DWI to monitor response to medical therapy:
- Good therapeutic response: DWI signals change from initial high signal intensity to low signal intensity, which suggest the disappearance of purulent content within the abscess core
- Good to differentiate between neoplastic vs abscess
- Fungal abscess
- Restricted diffusion in the projections and wall but not in the core of the abscess.
- MRS (Cartes- Zumelzu et al., 2004; Luthra et al., 2007)
- Elevated peaks of metabolites associated with hypoxia and cellular breakdown
- Elevated peaks are seen corresponding to lipids/lactate, succinate, acetate, and amino acids (alanine, valine, leucine, and isoleucine)-radiopedia
- Can may help in distinguishing the subtypes of abscess
- Decrease/absent in neural markers: N-acetyl aspartate (NAA) and creatine (Cr)
- Good to differentiate between neoplastic vs abscess
- Difference vs tumour
Features | Tumour | Abscess |
CT/MRI | Less uniform ring enhancing thickness | More uniform ring enhancing thickness |
Relatively less oedema | Relatively more oedema | |
Relatively slower growing | Relatively faster growing | |
DWI | - Core DWI hypointense, high ADC values - Wall DWI hyperintense, low ADC values | - Core DWI hyperintense, low ADC values - Wall DWI hypointense, high ADC values |
MRS | - Decrease in NAA and creatine peaks - Increase in choline, lipids and lactate peaks. | - Decrease/absent in NAA and Cr peaks - Increase in lipids/lactate, succinate, acetate, and amino acids (alanine, valine, leucine, and isoleucine) peaks |
Treatment
Main
- Surgical excision or drainage then long term antibiotics (6-8 wks iv + 4-8 wks oral )
- Treat primary source of infection
Supportive
- Anti convulsants
- If patients have seizure
- In temporal lobe
- Use for a year
- Steroid
- Use for very short course
- Controversial
- Mechanism
- Dex can reduce an inflammatory response in the subarachnoid space contributes significantly to morbidity and mortality.
- Advantage
- Can reduce brain swelling with improvement of mass effect and impending herniation.
- Disadvantage
- Decreased host immune response to infection,
- Can delay formation of the abscess wall → more destruction of perilesional viable brain tissue + delayed containment of the abscess.
- Can cause a fake reduction in enhancement
- Evidence
- Helweg- Larsen et al., 2012
- Steroid treatment prior to surgery does not appear to significantly change outcome
- In a retrospective study 21% treated patients versus 23% non- treated patients had GOS less than 3 at discharge
- Functional outcome in patients who received steroids after surgery was also not significant with a GOS less than 3 in 25% on steroids versus 20% without steroids
- Aras et al., 2016
- Use of steroids was associated with higher mortality compared to non- steroid group (15.6% vs. 3.9%)
Pure antibiotics
- Not good
- Organism well encapsulated away
- Poor blood supply to abscess
- Acidic condition denature antibiotics
- Can be used if
- Given before cerebritis stage
- If S&S <2 wks
- Patients shows sign of improvement within first week
- Very small lesion (<1.7cm)
- Indicated if
- Poor surgical candidate (pure local anaesthesia with stereotactic approach can be done in almost all patients with normal clotting)
- Multiple abscess if small
- Abscess in poorly accessible location (brain stem)
- Concomitant meningitis/ependymitis
Agents
- Bacterial
- Choice based on
- Suspected source of abscess (i.e. sinusitis vs. otogenic vs. post- traumatic),
- Direct adjacent source of infection (i.e. sinusitis, otogenic)
- 3rd generation cephalosporins + metronidazole for additional anaerobic cover
- Direct inoculation such as posttrauma or post brain surgery
- 3rd generation cephalosporins + Vancomycin for additional Gram- positive coverage
- Pharmacokinetics of CSF penetration,
- Duration
- 6-8 weeks
- Guided by clinical and radiographic response
- Neuroimaging and CRP markers allowing titration of antibiotic therapy duration
- Route of administration (i.e. intravenous vs. intraventricular)
- Given intravenously at high dose to facilitate blood brain barrier penetration
- Penicillin allergy give chloramphenicol
- If no staph can use Pencilin G instead of nafcillin
- MRSA neg: nafcillin
- Fungal
- Voriconazole for aspergillus infection and
- Amphotericin B
- Candida (Candida albicans)
- Mucormycosis (Mucor and Rhizopus spp.)
- Cryptocoocus neoformans
- Aspergillus candida
- AIDS + toxoplasmosis gondii: sulfadiazine + pyrimethamine
Surgical treatment
- Indications
- If it expands towards ventricles
- Neurological deterioration
- Not managing with antibiotics
- Significant mass effect
- Difficulty in diagnosis
- Raised ICP
- Traumatic abscess with FB
- Fungal abscess
- Multi loculated
- Large >2.5cm
- Options
- Needle aspiration: main (Radoi et al., 2013)
- Pros
- Fast
- Cheap
- Easy to do
- Low complication
- Low seizure risk
- Can be done in most pt
- Can be done for deep lesion
- Cons
- Is not a complete removal of infective material → higher recurrence (70% recurrence)
- Surgical drainage
- Pros
- Prevent recollection
- Shorten antibiotics time
- Can remove FB
- For multiloculated
- Cons
- More complications,
- More complex procedure
- Can be only performed in the chronic phase (late capsule)
- Surgical excision
- Can only be done during the late capsule stage
- Abscess removed like a tumour
- Excising abscesses in their entirety can improve radiological appearances but with additional risk, particularly of postoperative seizure. Smaller abscess can simply be needle aspirated under image guidance (Radoi et al., 2013).
- Indicated for
- Superficial and large abscesses
- Has foreign body
- Fungal infection
- Norcardia abscesses
- Antibiotic or needle drainage resistant lesions
- Advantage
- Length of time on antibiotics can be shortened after excision
- If there is multiple abscesses
- If abscess has not been confirmed yet
- The largest lesion or the one causing the most symptoms
- Once the diagnosis of abscess is confirmed
- Any lesion≥ 2.5cm diameter
- Lesions causing significant mass effect
- Enlarging lesions
Outcome
Mortality • Rupture into ventricle ◦ EVD and antibiotics • Brain herniation | 5% |
Neurological disability | 45% |
Late focal or generalized seizure | 27% |
Hemiparesis | 29% |
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