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Cerebral Abscess: Cerebral Abscess: What’s the Data? Lee Selznick, M.D. March 23rd, 2005

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Page 1: Cerebral Abscess

Cerebral Abscess:Cerebral Abscess:What’s the Data?

Lee Selznick, M.D.March 23rd, 2005

Page 2: Cerebral Abscess

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Total Articles (1902Total Articles (1902--2005): 45412005): 4541

In English Language: 2957In English Language: 2957

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Cerebral Abscess: The Data

*Medline*Medline

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Cerebral Abscess

• Epidemiology– Risk factors– Bacteriology

• Diagnostics (Radiology/Pathology)– Diagnosing a ring-enhancing lesion– Staging an abscess

• Treatment– Surgical versus non-surgical– Steroids

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Epidemiology

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Medline Search:Medline Search:

•• Subject:Subject: cerebral abscess

•• Limit to:Limit to: epidemiology, etiology, microbiology

•• Data:Data: case series, case reports, reviews

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EpidemiologyLargest series:Largest series:

“Brain abscess: a review of 400 cases” - J J Neurosurg Neurosurg 55:79455:794--799, 1981799, 1981 (ChinaChina)

Largest series in U.S.:Largest series in U.S.:

“Trends in the management of bacterial brain abscesses: A review of 102 cases over 17 years”- Neurosurgery 23(4):451Neurosurgery 23(4):451--458, 1988458, 1988 (RosenblumRosenblum,, UCSFUCSF)

Most current large series:Most current large series:

“Bacterial brain abscess: microbiological features, epidemiological trends and therapeutic outcomes”- QJM 95: 501QJM 95: 501--509, 2002509, 2002 (Taiwan, 123 casesTaiwan, 123 cases)

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Epidemiology•Incidence: 1500-2500 cases/year in the U.S.

•1-2% of intracranial space-occupying lesions in the U.S.

•Age/Sex: M > F (1.5-3:1)

•Risk factors: ((MampalamMampalam & Rosenblum, UCSF, 1970& Rosenblum, UCSF, 1970--1986)1986)Out of 96 patients with cerebral abscess:

• 21% without known risk factor/source• 19% with local infectionlocal infection (sinusitis/mastoiditis)• 18% with cardiac sourcecardiac source

• congenital cyanotic heart disease (children)• 17% with prior intracranial surgeryintracranial surgery• 9% with prior cranial traumatrauma• 7% with pulmonarypulmonary source

• A-V shunts (adults, ROW syndrome)• 5% with immunosuppressionimmunosuppression (HIV, transplant)

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Epidemiology•Source:

• Local (@40%)• middle ear/mastoiditis to temporal lobe or cerebellum• frontal sinus to frontal lobe• trauma/surgery• single > multiple

• Hematogenous (@40%)• multiple• distal MCA, gray-white junction• Adult: pulmonary fistula (HHT)• Peds: cyanotic heart disease

• Unknown (@20%)

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Epidemiology• Microbiology ((MampalamMampalam & Rosenblum, UCSF, 1970& Rosenblum, UCSF, 1970--1986)1986)

• 55% Single organism• 75% Aerobic (streptococcusstreptococcus > staph aureus, haemophilus)• 20% Anaerobes

• 20% Multiple• 25% Sterile cultures

• Immunosuppressed (Neurology 50(1): 1(Neurology 50(1): 1--17, 1997 17, 1997 –– HIV practice guidelines)HIV practice guidelines)• toxoplasmosistoxoplasmosis (*most common CNS mass lesion)• fungal• mycobacterium

• Neonates:• proteusproteus (J(J NeurosurgNeurosurg 69: 87769: 877--882, 1988 882, 1988 –– review of 30 cases)review of 30 cases)• citrobacter• bacteroides

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Diagnostics (Radiology/Pathology)

Medline Search:Medline Search:

•• Subject:Subject: cerebral abscess

•• Limit to:Limit to:CSF, diagnosis, radiography, radionucleotide imaging, u/s

•• Data:Data: case series, case reports, small case-control studies, animal studies (staging)

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Ring-enhancing LesionsDDx (Osborne)• Common:

••GBM GBM ••MetastasisMetastasis••AbscessAbscess•Granuloma (fungal, TB)•Resolving hematoma•Subacute Infarct

• Less common:•Thrombosed AVM•Active MS plaque

•Uncommon:•Thrombosed aneurysm•Lymphoma•Radiation necrosis

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Radiology – Abscess vs. Neoplasm• CT

• thin, smooth ring versus nodular ring on contrast scan

• MRI ((Acta Radiol supplActa Radiol suppl. 369: 754, 1986). 369: 754, 1986)• HYPOintense ring versus heterogeneous signal on T2

AbscessAbscess GBMGBMABSCESSABSCESS

*may be thinner on medial surface (50%)

*thinner ring if immunosuppressed

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Radiology – Abscess vs Neoplasm• MR spectroscopy (AJNR 23: 1369(AJNR 23: 1369--1377, 2002)1377, 2002)

• acetate and amino acid peaksacetate and amino acid peaks• present in 4 of 5 abscesses• absent in 7 of 7 neoplasms

• MR diffusion (J(J NeurosurgNeurosurg 97: 110197: 1101--1107, 2002)1107, 2002)• 16 of 16 abscesses with restricted diffusionrestricted diffusion• 16 of 16 neoplasms with unrestricted diffusion(AJNR 22: 1738(AJNR 22: 1738--1742, 2001)1742, 2001)•1 of 3 abscesses with unrestricted diffusion•1 of 13 neoplasms with restricted diffusion

• Leukocyte scan (radionucleotide): (Neurosurgery 16: 23Neurosurgery 16: 23--26, 1985)26, 1985)• 16 patients w/ mass lesion c/w tumor vs abscess (ring-enhancing)• positivepositive in 4 of 5 abscesses (effect of antibiotics?) • negative in 10 of 11 neoplasms (extensive necrosis/inflammation?)• takes 6-24hrs to obtain imaging

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StagingBritt & Enzmann (1979-1983)

• Dog model of cerebral abscess (J (J Neurosurg Neurosurg 55: 59055: 590--603, 1981)603, 1981)

• 19 “cases” and 2 controls

• direct injection of alpha strep into left parietal lobe

• radiological and pathological correlation

• Human pre-operative staging (J (J Neurosurg Neurosurg 59: 97259: 972--989, 1983)989, 1983)

• small, non-randomized study

• 14 patients, no controls

• prospective (?)

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Staging

perivascular polymorphonuclearinfiltrate marked

cerebral edema around lesion

+/- enhancement,May be patchy or ring-like

Irregular area of low density

Early Early CerebritisCerebritis(day 1(day 1--3)3)

PathPost-Contrast CT

Pre-Contrast CT

StageI

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Staging

Mixed poly/mx infiltrateMaximal size of necrotic centerFibroblasts around necrotic centerMaximal cerebral edema

Typical ring enhancement

May be solid if small

Large area of low density

Late Late CerebritisCerebritis(days 4(days 4--9)9)

PathPost-Contrast CT

Pre-Contrast CT

StageII

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Maturing collagen capsule (less developed on ventricular side)Less inflammationVascularity around capsule at max

Ring enhancement

May be thinner on ventricular side

Faint ring separates low density necrotic center from low density surrounding edema

Early Early CapsuleCapsule

(day 10(day 10--13)13)

PathPost-Contrast CT

Pre-Contrast CT

StageIII

Staging

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Staging

Completed collagen capsuleReactive gliosis with less edema

Ring enhancement(usually thin/dense)May be thinner on ventricular side

Faint ring separates low density necrotic center from low density surrounding edema

Late Late CapsuleCapsule

(day 14+)(day 14+)

PathPost-Contrast CT

Pre-Contrast CT

StageIV

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Treatment

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Medline Search:Medline Search:

•• Subject:Subject: cerebral abscess

•• Limit to:Limit to: drug therapy, surgery, therapy

•• Data:Data: case series and case reports

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History• 1876: Sir William Macewen

• Pyogenic Infectious Diseases of the Brain and Spinal Cord, 1893• First to propose operative management for brain abscess• Advocated abscess drainage

• 1926: Walter Dandy (JAMA 87: 1477(JAMA 87: 1477--1478, 1926)1478, 1926)• First to advocate aspiration as primary treatment

• 1936: C. Vincent ((GazGaz. Med. Fr., 43: 93. Med. Fr., 43: 93--96, 1936)96, 1936)• First to advocate complete excision as primary treatment

• 1971: Heinemann and Baude (JAMA 218: 1542(JAMA 218: 1542--1547, 1971)1547, 1971)• First to suggest medical management alone (cerebritis)

• 1975: Chow (West. J. Med., 122: 167(West. J. Med., 122: 167--171, 1975)171, 1975)

•First non-surgical cure of encapsulated abscess (Listeria)

• 1976-1980: publications advocate CT-guided stereotactic aspiration

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Aspiration • CT, MRI, or U/S guided• GoalsGoals

• confirm diagnosis• identification of organisms/sensitivity• remove mass effect• remove bacterial “load” and improve local environment for Abx

• Relative IndicationsRelative Indications• single or multiple abscesses• superficial or deep• cerebritis or capsule stage• after medical therapy alone if: (J(J NeurosurgNeurosurg 52: 21752: 217--225, 1980)225, 1980)

• no decrease in size within 4wks• increase in size• decline in neurological status

•• Start antibiotics AFTER aspiration Start antibiotics AFTER aspiration ((Neurosurgery Neurosurgery 23(4): 45123(4): 451--458, 1988)458, 1988)• review of 102 cases (1970-1986)• 30% versus 4% sterile cultures if abx given pre-op

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Surgical Excision • GoalsGoals

• confirm diagnosis• identification of organisms/sensitivity• remove mass effect

• Relative IndicationsRelative Indications• single abscess• superficial, non-eloquent location• well-formed (capsule stage)• especially for:

• traumatic, retained foreign body (J (J Neurosurg Neurosurg 28: 16628: 166--168, 1968)168, 1968)• recurrent infection 36 years after trauma

• fungal (J (J NeurolNeurol. . NeurosurgNeurosurg. . PsychiatrPsychiatr., 36: 758., 36: 758--768, 1973)768, 1973)• risk of recurrence (within capsule wall)

• multiloculated• cerebellar

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Medical Therapy Indications • Black (J (J NeurosurgNeurosurg 38: 70538: 705--709, 1973)709, 1973)

• able to culture bacteria from abscess (ave. 5cm) despitegood concentration of antibiotics within cavity

• all failed medical management (6 patients)

• Rosenblum (J(J NeurosurgNeurosurg 52: 21752: 217--225, 1980)225, 1980)• Series of 12 patients• abscesses that resolved with antibiotics alone (8) were 1.7cm

vs. 4cm average for those ultimately requiring surgery (4)• no abscess larger than 2.5cm2.5cm resolved without surgical intervention• first decrease in abscess size within a mean of 2.4wk (range: 1-4wks)• resolution of contrast enhancement by 3.5 months

• Rosenblum ((Clin Neurosurg Clin Neurosurg 33: 60333: 603--632, 1986)632, 1986)• literature review of nonoperative management (1975-1985)• 23 articles, 67 cases treated w/ medical therapy alone• Outcome of five largest series (50 cases total):

• 74% overall success rate• 4% mortality

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Medical Therapy Indications Relative Indications: Relative Indications:

•• known source/organismknown source/organism•• cerebritiscerebritis > capsule stage> capsule stage•• good neurological statusgood neurological status•• multiple abscessesmultiple abscesses•• small size (1.5small size (1.5--3.0cm)3.0cm)•• bleeding diathesisbleeding diathesis•• severe medical severe medical comorbiditiescomorbidities

Recommended ProtocolRecommended Protocol•• weekly CT first 4 weeksweekly CT first 4 weeks•• then monthly until: then monthly until:

•• lack of contrast enhancementlack of contrast enhancement•• off antibiotics for 2 weeksoff antibiotics for 2 weeks

•• rescan w/ any clinical deteriorationrescan w/ any clinical deterioration•• surgery if:surgery if:

•• increase in size at any timeincrease in size at any time•• no change after 4 weeks of antibiotics no change after 4 weeks of antibiotics

•• continue continue abx abx for at least 6for at least 6--8weeks8weeksObanaObana & Rosenblum& Rosenblum ((Neurosurg ClinNeurosurg Clin 3(2): 359, 1992)3(2): 359, 1992)

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Steroids: Good or BadBackground (Pathophysiology)• Chemotaxis Chemotaxis of of polyspolys within 1 hour

• continue to enter for 24hrs• remain for 1-2 days• bacteriocidal activities

• Chemotaxis Chemotaxis of of monocytesmonocytes//mxmx w/in 24hrs• continue to enter for first week• major bacteriocidal action w/in abscess• stimulate formation of capsulecapsule and angiogenesisangiogenesis

• SteroidsSteroids• impair chemotaxis of polys & monocytes/mx• impair formation of capsule• may reduce antibiotic penetration (Arch Intern Med 93: 850(Arch Intern Med 93: 850--861, 1954)861, 1954)

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Steroids: Animal Models

• Bohl et al. (Adv. (Adv. Neurosurg Neurosurg 9: 235, 1981)9: 235, 1981)– S. aureus abscess in cats– Steroids reduce edema, inflammation, and encapsulation

• Neuwelt et al. (J (J Neurosurg Neurosurg 61: 43061: 430--439, 1984)439, 1984)– E. coli abscess in rats– Steroids decrease macrophages and inhibit gliosis

• Quartey et al. (J (J Neurosurg Neurosurg 45: 30145: 301--310, 1976)310, 1976)– Strep and Staph abscesses in rabbits– Steroids decrease wbc access, organism killing, and encapsulation

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Steroids: Human Data• Rosenblum et al. (J (J Neurosurg Neurosurg 49: 65849: 658--668, 1978)668, 1978)

– NO relationship between presence or duration of steroids and mortality (36 patients, retrospective, non-randomized review)

• Mampalam & Rosenblum (Neurosurgery 23(4): 451(Neurosurgery 23(4): 451--458, 1988)458, 1988)– Review of 102 cases (1970-1986)– Steroids correlated with poorer neurological outcome

(worse initial neurological grade also)

• Rosenblum ((Neurosurgery Neurosurgery 36(1): 7636(1): 76--86, 1995)86, 1995)– Review of 16 cases with multiple abscess– Steroids did not correlate with outcome

• Takehsita et al. (Japan) Acta Neurochir Acta Neurochir 140: 1263140: 1263--1270, 1998)1270, 1998)– Review of 113 cases (1976-1995)– 24 treated with steroids (all with impaired consciousness and edema)– Steroids did not correlate with outcome

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Steroids: Recommendations•• Useful for reduction of symptomatic mass Useful for reduction of symptomatic mass

effect caused by edemaeffect caused by edema• Should be avoided in early stages if possible• Use of steroids may decrease enhancement

– If cerebritis (Britt & (Britt & EnzmannEnzmann, J , J Neurosurg Neurosurg 59: 97259: 972--989, 1983)989, 1983)

• Withdrawal of steroids may increase enhancement– Does not correlate clinically (Radiology 135: 663(Radiology 135: 663--671, 1980)671, 1980)

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Morbidity/Mortality

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•• Subject:Subject: cerebral abscess

•• Limit to:Limit to: complications, mortality

•• Data:Data: case series and case reports

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• Reduced mortality since use of CT scan• 3030--50%50% mortality pre-CT era• 55--10%10% mortality post-CT era

• Poor outcome highly associated with:• initial neurologic neurologic gradegrade (J (J Neurosurg Neurosurg 55: 79455: 794--799, 1981)799, 1981)

(review of 400 cases from China)• intraventricularintraventricular rupturerupture ((Acta NeurochirActa Neurochir : 1263: 1263--1270, 1998)1270, 1998)

• review of 113 patients from Japan• odds ratio of 24.5 (95% CI 3.04-197.9)• 39% mortality versus 3.4%

•• sepsissepsis (QJM 95: 501(QJM 95: 501--509, 2002)509, 2002)(review of 123 cases from Taiwan)

• High risk of seizures• 25% pre-operative risk ((Neurosurgery Neurosurgery 23(4): 45123(4): 451--458, 1988)458, 1988)• 30-50% in most series ((OsenbachOsenbach, , Neurosurg Clin Neurosurg Clin 3(2): 4033(2): 403--420, 1992)420, 1992)• mean latency for onset up to 3.5 years (Brain 96: 259(Brain 96: 259--268, 1973)268, 1973)• usually well-controlled with anti-convulsants

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THE END