BRAIN ABSCESS November 20, 2006 Gebre K Tseggay, MD

BRAIN ABSCESS Introduction Brain abscess is rare but life-threatening infection. Accounts for ~ 1 in 10,000 hospital admissions in US ( 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)

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

D IRECT 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 SPREAD (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 OFBRAIN ABSCESS MICROBIOLOGY OF BRAIN ABSCESS AGENT FREQUENCY (%) Streptococci ( S. intermedius, including S. anginosus )60–70 Bacteroides and Prevotella spp.20–40 Enterobacteriaceae23–33 Staphylococcus aureus10–15 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 mastoiditisStreptococci (anaerobic or aerobic), Bacteroides and Prevotella spp., Enterobacteriaceae Sinusitis (frontoethmoid or sphenoid)Streptococci, Bacteroides spp., Enterobacteriaceae, Staph. aureus, Haemophilus spp. Dental sepsisFusobacterium, Prevotella and Bacteroides spp., streptococci Penetrating trauma or postneurosurgicalS. 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

PATHOPHYSIOLOGY of 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

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

CLINICAL MANIFESTATIONS Brain 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 abscesses Headache Drowsiness Inattention Mental function deterioration Hemiparesis Motor speech disorder Temporal lobe abscesses Ipsilateral headache Aphasia Visual field defects Parietal lobe abscesses Headache Visual field defects Endocrine disturbances Cerebellar abscesses Nystagmus Ataxia Vomiting Dysmetria

CLINICAL MANIFESTATIONS OF BRAIN ABSCESS Headache70% Fever45-50 Focal neurologic findings>60 Triad of above three <50 Altered mental status <70 Nausea/vomiting25-50 Seizures25–35 Nuchal rigidity25 Papilledema25 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 glucose CSF 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 MARKERS

SPINAL EPIDURAL ABSCESS

SPINAL EPIDURAL ABSCESS SPINAL EPIDURAL ABSCESS INTRODUCTION 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 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)AFP®Vol. 65/No. 7 (April 1, 2002) NEJM 2006;355: Nov 9,2006

PATHOGENESIS PATHOGENESIS 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

PATHOGENESIS PATHOGENESIS SPINAL 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

MICROBIOLOGY SPINAL EPIDURAL ABSCESS The most common pathogens are: Staph aureus >60% Streptococci18% Aerobic GNR13% Polymicrobial 10% TB may cause up to 25% in some areas

CLINICAL MANIFESTATIONS SPINAL 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 CULTURES YIELD OF CULTURES SPINAL EPIDURAL ABSCESS Abscess fluid aspirate90% Blood culture62% CSF* 19% *But, LP not advisable (may be c/b meningitis, subdural abscess, & not very helpful anyway)

TREATMENT TREATMENT SPINAL 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: Factors That Affect Outcome in Spinal Epidural Abscess

Spinal Epidural Abscess Complications Mortality ~ 5% Paralysis 4-22% –Paralysis existing for more than hrs unlikely to reverse. Darouiche NEJM Nov. 9, 2006

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/ 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 % 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 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 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 non- responders 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 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 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.