CNS ABSCESSES

Nov 10, 2003 Gebre K Tseggay, MD

CNS ABSCESSES
Focal pyogenic infections of the central nervous system Exert their effects mainly by: Direct involvement & destruction of the brain or spinal cord Compression of parenchyma Elevation of intracranial pressure Interfering with blood &/or CSF flow

Include: Brain abscess, subdural empyema, intracranial epidural abscess, spinal epidural abscess, spinal cord abscess

BRAIN ABSCESS
Accounts for ~ 1 in 10,000 hospital admissions in US (1500-2500 cases/yr) Major improvements realized in diagnosis & management the last century, & especially over the past three decades, with:

BRAIN ABSCESS
Was uniformly fatal before the late 1800s Mortality down to 30-60% from WWII-1970s
Introduction of abx (penicillin, chloramphenicol...) newer surgical techniques

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

Advent of CT scanning (1974), MRI Stereotactic brain biopsy/aspiration techniques Further improvement in surgery Newer abx (e.g. cephalosporins, metronidazole..) Better treatment of predisposing conditions

CHANGES IN EPIDEMIOLOGY OF BRAIN ABSCESS

(in the last 2-3 decades)

Marked drop in mortality overall Lower incidence of otogenic brain abscesses

improved treatment of chronic ear infections

With increase in No. of immunosuppressed patients:

increased incidence of brain abscess seen in that population (Transplant, AIDS,) More incidence of brain abscess caused by opportunistic pathogens (fungi, toxo)

PATHOPHYSIOLOGY
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 experimental animal models):

Days 1-3: early cerebritis stage Days 4-9: late cerebritis stage Days 10-14: early capsule stage > day14: late capsule stage

PATHOGENESIS
Direct spread from contiguous foci (40-50%) Hematogenous (25-35%) Penetrating trauma/surgery (10%) Cryptogenic (15-20%)

DIRECT SPREAD
(from contiguous foci)

Occurs by:
Direct extension through infected bone Spread through emissary veins, diploic veins, local lymphatics

The contiguous foci include:

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)

HEMATOGENOUS SPREAD
(from remote foci)

Sources:
Empyema, lung abscess, bronchiectasis, endocarditis, wound infections, pelvic infections, intra-abdominal source, etc may be facilitated by cyanotic HD, AVM.

Results in brain abscess(es) at middle cerebral artery distribution Often multiple

PREDISPOSING CONDITION & LOCATION OF BRAIN ABSCESS

Otitis/mastoiditis Temporal lobe, Cerebellum Frontal/ethmoid sinusitis Frontal lobe Sphenoidal sinusitis Dental infection Remote source Frontal lobe, Sella turcica Frontal > temporal lobe. Middle cerebral artery distribution (often multiple)

Microbiology of Brain Abscess

Dependent upon:
Site of primary infection Patients underlying condition Geographic location

Usually streptococci and anaerobes Staph aureus, aerobic GNR common after trauma or surgery 30-60 % are polymicrobial

Predisposing Conditions & Microbiology of Brain Abscess

Predisposing Condition
Otitis media or mastoiditis

Usual Microbial Isolates

Streptococci (anaerobic or aerobic), Bacteroides and Prevotella spp., Enterobacteriaceae
Streptococci, Bacteroides spp., Enterobacteriaceae, Staph. aureus, Haemophilus spp. Fusobacterium, Prevotella and Bacteroides spp., streptococci

Sinusitis (frontoethmoid or sphenoid)

Dental sepsis

Penetrating trauma or postneurosurgical

S. aureus, streptococci, Enterobacteriaceae, Clostridium spp.

PPID,2000

PREDISPOSING CONDITION
Lung abscess, empyema, bronchiectasis

USUAL MICROBIAL ISOLATES

Fusobacterium, Actinomyces, Bacteroides Prevotellaspp., streptococci, Nocardia S. aureus, streptococci Streptococci, Haemophilus spp. Aerobic gram-negative bacilli, Aspergillus Mucorales, Candidaspp. Aspergillus spp., Candida spp., Mucorales, Enterobacteriaceae, Nocardia spp., Toxoplasma gondii Toxoplasma gondii, Nocardia spp., Mycobacterium spp., Listeria monocytogenes, Cryptococcus neoformans

Bacterial endocarditis
Congenital heart disease Neutropenia Transplantation

HIV infection

PPID, 2000

MICROBIOLOGY OF BRAIN ABSCESS

AGENT
Bacteroides and Prevotella spp.

FREQUENCY (%)
6070 2040

Streptococci (S. intermedius, including S. anginosus)

Enterobacteriaceae
Staphylococcus aureus Fungi *

2333
1015 1015

Streptococcus pneumoniae
Haemophilus influenzae Protozoa, helminths (vary geographically)

<1
<1 <1

*Yeasts, fungi (Aspergillus Agents of mucor Candida Cryptococci Coccidiodoides

Cladosporium trichoides Pseudallescheria boydii)

Protozoa, helminths (Entamoeba histolytica, Schistosomes Paragonimus

Cysticerci)
CTID,2001

CLINICAL MANIFESTATIONS
Non-specific symptoms Mainly due to the presence of a spaceoccupying lesion
H/A, N/V, lethargy, focal neuro signs , seizures

Signs/symptoms influenced by
Location Size Virulence of organism Presence of underlying condition

CLINICAL MANIFESTATIONS
OF BRAIN ABSCESS Headache Fever Altered mental status Triad of above three Focal neurologic findings Nausea/vomiting Seizures Nuchal rigidity Papilledema 70% 50 50-60 <50 50 25-50 2535 25 25

CTID,2001. PPID,2000

CLINICAL MANIFESTATIONS
Headache Often dull, poorly localized (hemicranial?), nonspecific
Abrupt, extremely severe H/A: think meningitis, SAH. Sudden worsening in H/A w meningismus: think rupture of brain abscess into ventricle (often fatal)

LOCATION & CLINICAL FEATURES

FRONTAL LOBE: H/A, drowsiness, inattention, hemiparesis, motor speech disorder, AMS TEMPORAL LOBE: Ipsilateral H/A, aphasia, visual field defect

PARIETAL LOBE: H/A, visual field defects, endocrine disturbances

CEREBELLUM: Nystagmus, ataxia, vomiting, dysmetria

DIFFERENTIAL DIAGNOSIS
Malignancy
Abscess has hypo-dense center, with surrounding smooth, thinwalled capsule, & areas of peripheral enhancement. Tumor has diffuse enhancement & irregular borders. SPECT (PET scan) may differentiate. CRP too?

CVA Hemorrhage Aneurysm Subdural empyema/ICEpidural abscess

DIAGNOSIS
High index of suspicion Contrast CT or MRI Drainage/biopsy, if ring enhancing lesion(s) are seen

IMAGING STUDIES
MRI
more sensitive for early cerebritis, satellite lesions, necrosis, ring, edema, especially posterior fossa & brain stem

CT scan 99m Tc brain scan

very sensitive; useful where CT or MRI not available Skull x-ray : insensitive, if air seen, consider possibility of brain abscess

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 ESR BC
LP

almost invariably elevated

Usually moderately elevated

Often negative BUT Should still be done
Contraindicated in patients with known/suspected brainabscess Risk of herniation 15-30% If done, may have normal CSF findings, but: Usually elevated CSF protein & cell count (lymphs) Unremarkable glucose & CSF cultures rarely positive

TREATMENT
Combined medical & surgical
Aspiration or excision empirical abx

Empirical antibiotics are selected based on:

Likely pathogen (consider primary source, underlying
condition, & geography)

Antibiotic characteristics: usual MICs, CNS

penetration, activity in abscess cavity

Modify abx based on stains Duration: usually 6-8 wks

after surgical excision, a shorter course may suffice

Armstrong ID, Mosby inc 1999

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

MEDICAL TREATMENT ONLY

[Better-vascularized cortical lesions more likely to respond to abx alone] [ Subcortical/white-matter lesions are poorly vascularized]

CTID,2001

SERIAL IMAGING IMPORTANT TO MONITOR RESPONSE

Before Rx

After completion of Rx

Armstrong ID,Mosby inc 1999

POOR PROGNOSTIC MARKERS

Delayed or missed diagnosis Inappropriate antibiotics. Multiple, deep, or multi-loculated abscesses Ventricular rupture (80%100% mortality) Fungal , resistant pathogens. Neurological compromise at presentation Short duration w severe AMS, Rapidly progressive neuro. Impairment Immunosuppressed host

Poor localization, especially in the posterior fossa (before CT)

Modified from CTID,2001

EPIDURAL ABSCESSES
Spinal > intracranial (9:1) Intracranially, the dura is adherent to bone True spinal epidural space is present posteriorly throughout the spine, thus posterior longitudinal spread of infection is common.
Anterior spinal epidural very rare (usually below L1 & cervical)

American Family Physician April 1, 2002

SPINAL EPIDURAL ABSCESS

INTRODUCTION
Rare, 0.2-1.2 per 10,000 hospital admissions Median age 50 yrs (35 yrs in IVDU) Thoracic>lumbar>cervical Majority are acquired hematogenously

COMMON PREDISPOSING CONDITIONS

HEMATOGENOUS SPREAD: from remote infections & w IVDU DIRECT SPREAD: Vertebral osteomyelitis, diskitis, decubitus ulcers, penetrating trauma, surgery, epidural catheters Via paravertebral venous plexus: from abdominal/pelvic infections

PATHOGENESIS
SPINAL EPIDURAL ABSCESS Often begins as a focal disc or disc-vertebral junction infection Damage of spinal cord can be caused by:
Direct compression Thrombosis, thrombophlebitis Interruption of arterial blood supply Focal vasculitis Bacterial toxins/mediators of inflammation

Even a small SEA may cause serious sequelae

MICROBIOLOGY
SPINAL EPIDURAL ABSCESS

The most common pathogens are: Staph aureus >60% Streptococci 18% Aerobic GNR 13% Polymicrobial 10%
(Note: TB may cause up to 25% in some areas)

CLINICAL MANIFESTATIONS
SPINAL EPIDURAL ABSCESS

Four clinical stages have been described: 1. Fever and focal back pain; 2. Nerve root compression with nerve root pain; shooting pain 3. Spinal cord compression with accompanying deficits in motor/sensory nerves, bowel/bladder sphincter function; 4. Paralysis (respiratory compromise may also be present if the cervical cord is involved).
Armstrong, ID, Mosby inc,2000

DIAGNOSIS
SPINAL EPIDURAL ABSCESS
(Thinking of it is key, in a pt with fever, severe, focal back pain)

MRI, CT Abscess drainage Blood cultures Routine Labs rarely helpful

ESR,CRP usually elevated, BUT non-specific WBC may or may not be elevated

LP contraindicated

D/DX
SPINAL EPIDURAL ABSCESS

Metastases Vertebral diskitis and osteomyelitis Meningitis Herpes Zoster infection Other disc/bone disease

TREATMENT
SPINAL EPIDURAL ABSCESS

Early surgical decompression/drainage

(preferably within first 24h)

Antibiotics
Empiric abx should cover Staph, strep, & GNR Duration of Rx : 4-6 weeks

(SEA/SDE)

90% epidural abscesses are spinal Most SEA occur in thoracic (the longest) Majority of SEA (>70%) are posterior to the cord Most SEA caused hematogenous spread & Staph aureus is the leading cause. 95% SDE are in intracranial Majority of SDE pts have associated sinusitis

INTRACRANIAL EPIDURAL ABSCESS

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 ABSCESS MICROBIOLOGY: Micraerophillic Strep, Propioni, Peptostrept, few aerobic gNR, fungi. Postop: Staph, GNR. CLINICAL MANIFESTATION: from SOL/ systmic
igns 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 Motly a complication of sinusitis, otitis media, mastoiditis. Most common complication of sinusitis (60% of such cases), mostly from frontal/ethmoid sinusitis. Trauma/post-op & rarely hematogenous M>F

SUBDURAL EMPYEMA Clinical Manifestations

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

(Armstrong, ID,1999, Mosby Inc)

PARASITIC BRAIN ABSCESS

Toxoplasmosis Neurocysticercosis Amebic Echinococcal

NOCARDIA 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 AIDS

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

Listeria, Nocardia, tb, fungi

BRAIN 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

(Aspergillus, Mucor ...)

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 SEQUELAE

Seizure in 30-60% Neuro deficits 30-50% Mortality 4-20%

YIELD OF CULTURES
SPINAL EPIDURAL ABSCESS

SOURCE

YIELD

Abscess fluid aspirate Blood culture CSF*

90% 62% 19%

*LP often contraindicated