BRAIN ABSCESS BRAIN ABSCESS

November 20, 2006

Gebre K Tseggay, MD

BRAIN ABSCESSBRAIN ABSCESSIntroductionIntroduction

• Brain abscess is rare but life-threatening infection.• Accounts for ~ 1 in 10,000 hospital admissions in US

(1500-2500 cases/yr)• It was uniformly fatal before the late 1800’s• Advances in diagnosis & management the last century,

& especially over the past three decades have lead to a significantly lower mortality.

• Mortality down to 30-60% from WWII-1970’s– Introduction of abx (penicillin, chloramphenicol...) – newer surgical techniques

• Mortality down to 0-24% over the past three decades, with:

– Advances in radiography [CT scanning (1974), MRI] – Advances in surgery– Stereotactic brain biopsy/aspiration techniques– Newer abx (e.g. cephalosporins, metronidazole..)– Better treatment of predisposing conditions

CHANGES IN EPIDEMIOLOGY OF

BRAIN ABSCESS (in the last 2-3 decades)

• Lower incidence of otogenic brain abscesses

• With increase in # of immunocompormised patients (transplant, AIDS,…), increased incidence of brain abscess seen in that population, including those caused by opportunistic pathogens (e.g., fungi, toxo, Nocardia)

PATHOGENESISPATHOGENESIS

• Direct spread from contiguous foci (40-50%)

• Hematogenous spread (25-35%)

• Penetrating trauma/surgery (10%)

• Cryptogenic (15-20%)

DDIRECT SPREADIRECT SPREAD

• From:• Otitis media & mastoiditis • Sinusitis• Dental infection (<10%), typically with molar

infections • Meningitis rarely complicated by brain abscess (more common

in neonates with Citrobacter diversus meningitis, of whom 70% develop brain abscess)

• By:– Direct extension through infected bone – Spread through emissary/diploic veins, local

lymphatics

HEMATOGENOUS SPREADHEMATOGENOUS SPREAD (from remote foci)(from remote foci)

• From: – empyema, lung abscess, bronchiectasis– endocarditis, – wound infections,– pelvic infections, intra-abdominal source,

etc…– may be facilitated by cyanotic HD, AVM.

• Abscess mostly at middle cerebral artery distribution, and often multiple

PREDISPOSING CONDITION LOCATION OF ABSCESS

Otitis/mastoiditis Temporal lobe,

Cerebellum

Frontal/ethmoid sinusitis Frontal lobe

Sphenoidal sinusitis Frontal lobe,

Sella turcica

Dental infection Frontal > temporal lobe.

Remote source Middle cerebral artery distribution (often multiple)

MICROBIOLOGY OFMICROBIOLOGY OF BRAIN ABSCESSBRAIN ABSCESS

AGENT FREQUENCY (%)

Streptococci (S. intermedius, including S. anginosus) 60–70

Bacteroides and Prevotella spp. 20–40

Enterobacteriaceae 23–33

Staphylococcus aureus 10–15

Fungi 10–15

Streptococcus pneumoniae <1

Haemophilus influenzae <1

Protozoa, helminths † (vary geographically) <1

*Fungi (Aspergillus Agents of mucor Candida Cryptococci Coccidiodoides Cladosporium trichoides Pseudallescheria boydii)†Protozoa, helminths (Entamoeba histolytica, Schistosomes Paragonimus Cysticerci)

CTID,2001

PREDISPOSING CONDITION USUAL MICROBIAL ISOLATES

Otitis media or mastoiditis Streptococci (anaerobic or aerobic), Bacteroides and Prevotella spp., Enterobacteriaceae

Sinusitis (frontoethmoid or sphenoid) Streptococci, Bacteroides spp., Enterobacteriaceae, Staph. aureus, Haemophilus spp.

Dental sepsis Fusobacterium, Prevotella and Bacteroides spp., streptococci

Penetrating trauma or postneurosurgical S. aureus, streptococci, Enterobacteriaceae, Clostridium spp.

PPID,2000

PREDISPOSING CONDITION USUAL MICROBIAL ISOLATES

Lung abscess, empyema, bronchiectasis Fusobacterium, Actinomyces, Bacteroides Prevotella spp., streptococci, Nocardia

Bacterial endocarditis S. aureus, streptococci

Congenital heart disease Streptococci, Haemophilus spp.

Neutropenia Aerobic gram-negative bacilli, Aspergillus Mucorales, Candidaspp.

Transplantation Aspergillus spp., Candida spp., Mucorales, Enterobacteriaceae, Nocardia spp., Toxoplasma gondii

HIV infection Toxoplasma gondii, Nocardia spp., Mycobacterium spp., Listeria monocytogenes, Cryptococcus

neoformans

PPID, 2000

PATHOPHYSIOLOGYPATHOPHYSIOLOGYof Brain Abscessof Brain Abscess

• Begins as localized cerebritis (1-2 wks)• Evolves into a collection of pus surrounded by a

well-vascularized capsule (3-4 wks)

• Lesion evolution (based on animal models):– Days 1-3: “early cerebritis stage”– Days 4-9: “late cerebritis stage”– Days 10-14: “early capsule stage”– > day14: “late capsule stage”

Cerebritis

http://pathology.mc.duke.edu/neuropath/cnslecture

Effect of Brain Abscess

– Direct destruction– Compression of parenchyma– Elevation of intracranial pressure– Interfering with blood &/or CSF flow

CLINICAL MANIFESTATIONSCLINICAL MANIFESTATIONSBrain AbscessBrain Abscess

• Usually non-specific symptoms

• Manifestations are influenced by • Location of abscess• Size of abscess• Virulence of organism• Presence of underlying condition

Clinical manifestations according to abscess location

• Frontal lobe abscessesHeadacheDrowsinessInattentionMental function deteriorationHemiparesisMotor speech disorder

• Temporal lobe abscessesIpsilateral headacheAphasiaVisual field defects

• Parietal lobe abscessesHeadacheVisual field defectsEndocrine disturbances

• Cerebellar abscessesNystagmusAtaxiaVomitingDysmetria

CLINICAL MANIFESTATIONSCLINICAL MANIFESTATIONS

OF BRAIN ABSCESS

Headache 70%

Fever 45-50

Focal neurologic findings >60

Triad of above three <50Altered mental status <70

Nausea/vomiting 25-50

Seizures 25–35

Nuchal rigidity 25

Papilledema 25

PPID,2005

HEADACHE in

Brain Abscess

• Usually non-specific, dull, and poorly localized.

• If abrupt & extremely severe headache: consider meningitis or SAH.

• Sudden worsening in H/A w meningismus: consider rupture of brain abscess into ventricle.

Diagnostic work-up

• MRI is the procedure of choice– more sensitive especially for early cerebritis, satellite

lesions, necrosis, ring, edema, especially for posterior fossa & brain stem abscesses

• CT scan with contrast enhancement is 95% sensitive

• Skull roentgenograms usually normal• Biopsy or aspiration needed for definitive

diagnosis• Laboratory findings often not helpful• Lumbar puncture contraindicated

LABORATORY TESTS BRAIN ABSCESS

•Aspirate: Gram/AFB/fungal stains & cultures, cytopathology (+/-PCR for TB)

•WBC Normal in 40%, only moderate leukocytosis in ~ 50%,

& only 10% have WBC >20,000

•CRP almost always elevated

•ESR Usually moderately elevated

•BC Often negative, BUT Should still be done

AVOID LP!! Risk of herniation 15-30%May even have normal CSF findings, but:Usually elevated CSF protein & cell count (lymphs)

Unremarkable CSF glucoseCSF culture rarely positive

PPID, 2005

MRI of the brain reveals a 2-cm, round, ring-enhancing lesion in the right lentiform nucleus with associated vasogenic edema and midline shift to the left. A, T1-weighted image reveals an ill-defined area of low attenuation. B, T1-weighted image after administration of gadolinium, which reveals ring enhancement of the abscess. C, T2-weighted image demonstrates hypointensity of the rim of the abscess with a large area of high signal intensity consistent with cerebral edema.

PPID,2005

DIFFERENTIAL DIAGNOSIS

• Malignancy– Abscess has hypodense center, with surrounding smooth, thin-

walled capsule, & areas of peripheral enhancement. – Tumor has diffuse enhancement & irregular borders.– PET scan may differentiate. – CRP??

• CVA• Hemorrhage• Aneurysm• Subdural empyema• Epidural abscess

TREATMENT

• Medical & surgical• Obtain Neurosurgical Consult ASAP

– Aspiration or excision

• Antibiotics Initially selected based on:

-Likely pathogen: considering primary source, underlying

condition, & geography

-Antibiotic characteristics: MICs for usual pathogens, CNS penetration, activity in abscess cavity

• Duration of abx: usually 6-8 wks • After surgical excision, a shorter course may

suffice

Antibiotics

• Empiric abx based on: Likely pathogen:

– considering primary source, – underlying condition,

– Geography

Antibiotic characteristics: – MICs for usual pathogens,– CNS penetration, – activity in abscess cavity

• Later, specific abx based on cultures• Duration of abx: usually 6-8 wks (+/-po abx)

– After surgical excision, a shorter course may suffice

Armstrong ID, Mosby inc 1999

ANTIBIOTICS TREATMENT ONLY (WITHOUT SURGERY)

• Only in pts with prohibitive surgical risk: – poor surgical candidate,– multiple abscesses– a dominant location– Abscess size <2.5 cm– concomitant meningitis, ependymitis– early abscess (cerebritis?) – In pt already showing improvement on abx

MONITOR RESPONSE CLOSELY WITH SERIAL IMAGING

Before Rx

After completion of Rx

Armstrong ID,Mosby inc 1999

• Delayed or missed diagnosis

• Inappropriate antibiotics

• Multiple, deep, or multi-loculated abscesses

• Poor localization, especially in the posterior fossa

• Ventricular rupture (80%–100% mortality)

• Fungal , resistant pathogens• Degree of neurological compromise at presentation• Rapidly progressive neuro. impairment• Immunosuppressed host

• Extremes of age

Modified from CTID,2001

POOR PROGNOSTIC MARKERSPOOR PROGNOSTIC MARKERS

SPINAL EPIDURAL ABSCESS

SPINAL EPIDURAL ABSCESSSPINAL EPIDURAL ABSCESSINTRODUCTION

• 0.2-2.8 per 10,000 hospital admissions• Incidence has doubled in the past 2 decades

(with increasing spinal instrumentation, IVDU, aging population)

• Median age 50 yrs (35 yrs in IVDU)• Thoracic > lumbar > cervical

SPINAL EPIDURAL ABSCESSESSPINAL EPIDURAL ABSCESSES

• A true spinal epidural space is present posteriorly throughout the spine, thus posterior longitudinal spread of infection is common.

• Anterior spinal epidural abscess is very rare (usually seen below L1 or cervical).

American Family Physician April 1, 2002

Predisposing Factors for Epidural Abscess

– Diabetes mellitus – Intravenous drug abuse – Alcoholism – Spinal procedure or surgery – Spinal trauma – Chronic renal failure– Malignancy – Immunodeficiency– Systemic source of infection

AFP® Vol. 65/No. 7 (April 1, 2002)

NEJM 2006;355:2012-20 Nov 9,2006

PATHOGENESISPATHOGENESIS Spinal Epidural Abscess

• HEMATOGENOUS SPREAD: from remote infections & IVDU

• DIRECT SPREAD: from vertebral osteomyelitis, diskitis, decubitus ulcers, penetrating trauma, surgery, epidural catheters

• Via paravertebral venous plexus: from abdominal/pelvic infections

PATHOGENESISPATHOGENESISSPINAL EPIDURAL ABSCESS

• Often begins as a focal disc or disc-vertebral junction infection

• Damage caused by:– Direct compression– Thrombosis, thrombophlebitis– Interruption of arterial blood supply– Focal vasculitis– Bacterial toxins/mediators of inflammation

• Even a small epidural abscess may cause serious sequelae

MICROBIOLOGYMICROBIOLOGYSPINAL EPIDURAL ABSCESSSPINAL EPIDURAL ABSCESS

The most common pathogens are:

• Staph aureus >60%

• Streptococci 18%

• Aerobic GNR 13%• Polymicrobial 10%

TB may cause up to 25% in some areas

CLINICAL MANIFESTATIONSCLINICAL MANIFESTATIONSSPINAL EPIDURAL ABSCESS

Four clinical stages have been described:

Stage I: Fever and focal back pain

Stage II: Nerve root compression with nerve root pain

Stage III: Spinal cord compression with accompanying deficits in motor/sensory nerves, bowel/bladder sphincter function

Stage IV: Complete Paralysis

Armstrong, ID, Mosby inc,2000

DIAGNOSIS SPINAL EPIDURAL ABSCESS

High index of suspicion in a pt with fever & severe focal back pain.

• MRI>CT

• Radionuclide studies (may identify the affected site)

• Abscess drainage(definitive dx)• Blood cultures (+ in 60%, especially w S. aureus)

• Routine Labs rarely helpful• ESR,CRP usually elevated, BUT non-specific• WBC may or may not be elevated

• LP not advisable

YIELD OF CULTURESYIELD OF CULTURESSPINAL EPIDURAL ABSCESS

• Abscess fluid aspirate 90%

• Blood culture 62%

• CSF* 19%

*But, LP not advisable (may be c/b meningitis, subdural abscess, & not very helpful anyway)

TREATMENTTREATMENTSPINAL EPIDURAL ABSCESS

• Treatment of choice: Surgical drainage as soon as possible + systemic antibiotics.

• Empiric Abx: for Staph (MRSA) + GNR• Duration of Rx : at least 6 weeks• If associated w infected SCS, remove all

hardware.• Monitor neurologic function closely

.

• Pt’s neurologic status immediately before surgery NEJM Nov.9,2006

• Age>60 years• Degree of thecal sac

compression>50% • Duration of cord symptoms >72 hours• Co-morbid conditions

Khanna RK, Malik GM, Rock JP, Rosenblum ML. : Neurosurgery 1996;39:958-64

Factors That Affect Outcome in Spinal Epidural Abscess

Spinal Epidural AbscessComplications

• Mortality ~ 5%• Paralysis 4-22%

– Paralysis existing for more than 24-36 hrs unlikely to reverse.

Darouiche NEJM Nov. 9, 2006

INTRACRANIAL EPIDURAL INTRACRANIAL EPIDURAL ABSCESSABSCESS

• Less common & less acute than SEA• Rounded, well-localized (because dura is

firmly adherent to bone)• Pathogenesis:

– Direct ext. from contiguous foci (sinusitis, otitis/mastoiditis)

– trauma,or surgery

INTRACRANIAL EPIDURAL ABSCESSINTRACRANIAL EPIDURAL ABSCESS

• MICROBIOLOGY: Micraerophillic Strep, Propioni, Peptostrept, few aerobic gNR, fungi. Postop: Staph, GNR.

• CLINICAL MANIFESTATION: from SOL/ systemic signs of infection

– Fever, HA, N/V, lethargy

• DX:- Think of it, imaging, drainage

• D/Dx: Tumor, other ICAbscesses

• Rx: Surgery + abx

• Mortality w appropriate Rx < 10%

SUBDURAL EMPYEMA

• 15-20 % of all focal intracranial infections• Mostly a complication of sinusitis, otitis media,

mastoiditis.• Most due to sinusitis (60% of such cases),

mostly from frontal/ethmoid sinusitis.• Trauma/post-op & rarely hematogenous• M>F• 95% SDE are in intracranial• Majority of SDE pts have associated sinusitis

SUBDURAL EMPYEMAClinical Manifestations

• Fever• Headache• Focal Neuro defects• Vomiting• Mental status changes• Seizures• Mass effect more common w SDE than w ICEADX: CT, MRI (LP contraindicated)Rx: Surgery . Abx (3-6 wks)

(Armstrong, ID,1999, Mosby Inc)

PARASITICPARASITIC BRAIN ABSCESS

• Toxoplasmosis

• Neurocysticercosis

• Amebic

• Echinococcal

NOCARDIA BRAIN ABSCESSNOCARDIA BRAIN ABSCESS

• Usually in immunosuppresed (CMI)• >50% no known predisposing factor• All pts w pulmonary nocardiosis should undergo

brain imaging to r/o subclinical CNS nocardiosis• Rx: Sulfa (T/S invitro synergy), imipenem,

ceftriaxone, amikacin, minocin– Duration of abx <a year.– Needle aspiration or surgical excision needed in

most.

• Relapse common

BRAIN ABSCESS IN AIDSBRAIN ABSCESS IN AIDS

• Toxoplasmosis is the most common• Seropositive• d/dx lymphoma• Often empiric Rx given & biopsy only non-

responders

• Listeria, Nocardia, tb, fungi…

BRAIN TBBRAIN TB

• Rare cause of brain abscess

• Usually in immunocompromised

• Tuberculoma is a granuloma (not a true abscess )

• Biopsy/drainage (send for PCR too )

FUNGAL BRAIN ABSCESS FUNGAL BRAIN ABSCESS (Aspergillus, Mucor ...)

• In immunocompromised

• Poor inflammatory response: less enhancement on CT.

• May present w much more advanced disease (seizure, stroke more common)

• High mortality

• Rx: aggressive surgery + antifungal

BRAIN ABSCESS SEQUELAEBRAIN ABSCESS SEQUELAE

• Seizure in 30-60%

• Neuro deficits 30-50%

• Mortality 4-20%

CTID,2001

• The valveless venous network that interconnects the intracranial venous system and the vasculature of the sinus mucosa provides an alternative route of intracranial bacterial entry.

• Thrombophlebitis originating in the mucosal veins progressively involves the emissary veins of the skull, the dural venous sinuses, the subdural veins, and, finally, the cerebral veins.

• By this mode, the subdural space may be selectively infected without contamination of the intermediary structure; a subdural empyema can exist without evidence of extradural infection or osteomyelitis.