opportunistic infections of the cns in patients with aids
TRANSCRIPT
Opportunistic Infections of the Opportunistic Infections of the CNS in Patients with AIDSCNS in Patients with AIDS
NupurNupur Mehta, HMS IIIMehta, HMS III
Gillian Lieberman, MDGillian Lieberman, MD
Nupur Mehta, HMS IIIGillian Leiberman, MD January 2004
Nupur Mehta, HMS IIIGillian Leiberman, MD
Mehta 01/26/04Mehta 01/26/0422
Patient EncounterPatient Encounter
•• HD is a previously healthy 32 HD is a previously healthy 32 y.oy.o. man . man who presents to ED with progressive who presents to ED with progressive decline in mental status, N/V, decreased decline in mental status, N/V, decreased PO intake, and severe unremitting PO intake, and severe unremitting headache for the past three daysheadache for the past three days
•• The differential diagnosis is broad, so The differential diagnosis is broad, so what do you do in the ED?what do you do in the ED?
Nupur Mehta, HMS IIIGillian Leiberman, MD
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Patient EncounterPatient Encounter•• Physical Exam Physical Exam –– AfebrileAfebrile, VS within normal limits, VS within normal limits
Physical exam otherwise unremarkablePhysical exam otherwise unremarkable•• Neurological Exam Neurological Exam –– HD is somnolent, HD is somnolent,
A&O to person only with A&O to person only with dysmetriadysmetria, gait , gait instability, ? of L facial droopinstability, ? of L facial droop
•• Toxicology Screen Toxicology Screen –– no toxinsno toxins•• CBC CBC –– showed WBC of showed WBC of 3.0 3.0 with with HctHct of 39.9of 39.9•• Electrolytes Electrolytes –– within normal limitswithin normal limits
Nupur Mehta, HMS IIIGillian Leiberman, MD
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Patient EncounterPatient Encounter
•• Lumbar Puncture showed Lumbar Puncture showed 3131 WBCWBC’’s/s/uLuL, , and and 621621 RBCRBC’’s/uLs/uL in 3in 3rdrd vial. On Gram vial. On Gram Stain, no microorganisms seenStain, no microorganisms seen
•• What imaging would you recommend?What imaging would you recommend?
Nupur Mehta, HMS IIIGillian Leiberman, MD
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Portable CXRPortable CXR
No evidence of consolidation or active infection
Image from BIDMC PACS
Nupur Mehta, HMS IIIGillian Leiberman, MD
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Our Patient Our Patient –– Axial CTAxial CT
Areas of edema
surrounding the lesions
Multiple high- attenuation
lesions spread throughout both
hemispheres representing
hemorrhagic foci
Mass Effect
Image from BIDMC PACS
Nupur Mehta, HMS IIIGillian Leiberman, MD
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Our Patient Our Patient –– Axial MRAxial MR
Both T1 and T2 scans show multiple hyper-intense lesions scattered throughout the cortex
T1 Image T2 Image
Images from BIDMC PACS
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Our Patient Our Patient -- WorkupWorkup
•• AntiAnti--HIV antibodies were found in the patientHIV antibodies were found in the patient’’s s serumserum
•• CD4 count was found to be CD4 count was found to be 5353 and the viral load and the viral load later found to be later found to be >100,000>100,000 copies/copies/mLmL
•• AntiAnti--toxoplasmatoxoplasma IgGIgG antibodies were antibodies were subsequently found confirming the diagnosis of subsequently found confirming the diagnosis of ToxoplasmosisToxoplasmosis
•• HD was subsequently admitted to BIDMC where HD was subsequently admitted to BIDMC where his condition rapidly improved on antihis condition rapidly improved on anti--protozoalprotozoal medications and supportive caremedications and supportive care
Nupur Mehta, HMS IIIGillian Leiberman, MD
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ToxoplasmosisToxoplasmosis
•• Most common CNS infection in patients Most common CNS infection in patients with AIDSwith AIDS
•• Caused by the organism Caused by the organism ToxoplasmaToxoplasma GondiiGondii a protozoa that colonizes up to a protozoa that colonizes up to 15% of people15% of people
•• 30% chance of reactivation when CD4 30% chance of reactivation when CD4 count <100count <100
•• Feline required for Feline required for ToxoplasmaToxoplasma lifecyclelifecycle
Nupur Mehta, HMS IIIGillian Leiberman, MD
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Our Patient Our Patient –– Treatment and F/UTreatment and F/U
•• HD was empirically treated with HD was empirically treated with PyrimethaminePyrimethamine, , Sulfadiazine, and Sulfadiazine, and LeukovorinLeukovorin for suspected for suspected ToxoToxo
•• He improved somewhat but had a recurrence of He improved somewhat but had a recurrence of acute MS change on the flooracute MS change on the floor
•• Rapid treatment with Rapid treatment with MannitolMannitol and and DexamethasoneDexamethasone averted possible averted possible uncaluncal herniationherniation
•• HD has since markedly improved and is currently HD has since markedly improved and is currently on HAART with an undetectable viral load and on HAART with an undetectable viral load and CD4 > 100CD4 > 100
Nupur Mehta, HMS IIIGillian Leiberman, MD
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Patient #2 Patient #2 -- ToxoplasmosisToxoplasmosisCharacteristic Findings
Ring enhancing lesions on MRI with surrounding edema
Evidence of mass effect, but no herniation
Image courtesy of S. Reddy, MD
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Other Opportunistic Infections of Other Opportunistic Infections of the CNSthe CNS
Nupur Mehta, HMS IIIGillian Leiberman, MD
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CNS Opportunistic InfectionsCNS Opportunistic Infections OverviewOverview
•• ToxoplasmaToxoplasma GondiiGondii•• AIDSAIDS--related CNS related CNS
lymphomalymphoma•• CMVCMV•• TBTB•• Fungal infectionsFungal infections•• NeurosyphilisNeurosyphilis
•• Progressive Multifocal Progressive Multifocal LeukoencephalopathyLeukoencephalopathy
•• HIV encephalopathyHIV encephalopathy•• Cryptococcus Cryptococcus
NeoformansNeoformans
Mass Effect No Mass Effect
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CNS Opportunistic InfectionsCNS Opportunistic Infections OverviewOverview
CT/MRI
Mass Effect No Mass Effect
Specific RxSteroids/Open Decompression
Toxo Serology
Herniation ?
Biopsy
Lumbar Puncture for Diagnosis
Adapted from Demeter, L www.utdol.com
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CNS Opportunistic InfectionsCNS Opportunistic Infections OverviewOverview
•• >500 cells/>500 cells/uLuL
•• <200 cells/<200 cells/uLuL
•• <100 cells/<100 cells/uLuL
•• CNS CNS neoplasmsneoplasms (likely (likely unrelated to HIV unrelated to HIV disease)disease)
CD4 Count CNS Pathology
•• TB, HSVTB, HSV
•• Toxoplasmosis, Toxoplasmosis, Cryptococcus, Cryptococcus, CMV, PML, FungiCMV, PML, Fungi
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AIDSAIDS--related CNS Lymphomarelated CNS Lymphoma
•• Nearly 100% of Nearly 100% of lesions are EBV lesions are EBV positive by PCRpositive by PCR
•• Typically have some Typically have some mass effectmass effect
•• Difficult to Difficult to differentiate from differentiate from ToxoplasmosisToxoplasmosis
Image reproduced from www.utdol.com
Nupur Mehta, HMS IIIGillian Leiberman, MD
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ToxoToxo or CNS Lymphoma?or CNS Lymphoma?
•• Nuclear Imaging with Nuclear Imaging with FDGFDG--PET shows areas PET shows areas of increased of increased metabolic activitymetabolic activity
•• Suggestive of Suggestive of lymphoma vs. lymphoma vs. ToxoplasmosisToxoplasmosis
Images from Goodman, PC (Ed). The Radiologic Clinics of North America: Imaging of the Patient with AIDS. W.B. Saunders Co, Philadelphia, PA. 1997
Nupur Mehta, HMS IIIGillian Leiberman, MD
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HIV EncephalopathyHIV Encephalopathy•• Primary infection of neural Primary infection of neural
cells with HIV, which have cells with HIV, which have tropism for CNStropism for CNS
Which causes…
Ventricular enlargement
Widening of the Sulci
Cortical and subcortical atrophy
Image reproduced from www.utdol.com
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HSV EncephalitisHSV Encephalitis
Image courtesy of S. Reddy, MD
•• Increased risk in Increased risk in immunosupressedimmunosupressed hostshosts
•• Predilection for medial Predilection for medial temporal lobetemporal lobe
•• Destruction mediated Destruction mediated by virus and host by virus and host immune responseimmune response
Nupur Mehta, HMS IIIGillian Leiberman, MD
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Progressive Multifocal Progressive Multifocal LeukoencephalopathyLeukoencephalopathy
•• Rare Rare demyelinatingdemyelinating disease caused by disease caused by DNA DNA PapovirusPapovirus (a.k.a. (a.k.a. polyomaviruspolyomavirus))
•• Route of transmission unclearRoute of transmission unclear•• 1%1%--4% of AIDS patients will develop PML 4% of AIDS patients will develop PML
if left untreatedif left untreated•• In one trial, 81% of patients with focal In one trial, 81% of patients with focal
brain lesions without mass effect had PML brain lesions without mass effect had PML
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Progressive Multifocal Progressive Multifocal LeukoencephalopathyLeukoencephalopathy
Characteristic Findings
Diffuse hyperintensities within the white matter with relative sparing of
gray matter and no evidence of mass effect
Image courtesy of B. Appagnani, MD
Nupur Mehta, HMS IIIGillian Leiberman, MD
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CryptococcalCryptococcal MeningoencephalitisMeningoencephalitis
•• AIDS defining illness AIDS defining illness in 40in 40--60% of patients60% of patients
•• Diagnosed with Diagnosed with Lumbar PunctureLumbar Puncture
•• Indolent course with Indolent course with symptoms of fever, symptoms of fever, malaise, and malaise, and headacheheadache
Image reproduced from www.utdol.com
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ProphylaxisProphylaxis
•• ToxoplasmosisToxoplasmosis
•• CMVCMV•• HSVHSV•• CryptococcusCryptococcus
•• TMP/SMX (doubles TMP/SMX (doubles for PCP prophylaxisfor PCP prophylaxis
•• GancyclovirGancyclovir•• AcyclovirAcyclovir•• Azoles (Azoles (FluconazoleFluconazole))
Opportunistic Infection Prophylaxis
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AcknowledgementsAcknowledgements•• Steve Reddy, MD Steve Reddy, MD •• Barbara Barbara AppignaniAppignani, MD, MD•• Martina Martina MorrinMorrin, MD, MD•• Larry Larry BarbarasBarbaras•• Pamela Pamela LepkowskiLepkowski•• Gillian Lieberman, MDGillian Lieberman, MD•• Jared Jared KesselheimKesselheim•• Margot Margot AlbeckAlbeck (a.k.a. lifesaver)(a.k.a. lifesaver)
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ReferencesReferences• Koralnik, Igor. Approach to HIV-infected patients with CNS Mass Lesions. In: UpToDate, Rose, BD (Ed),
UpToDate, Wellesley, MA, 2003• Porter, SB, Sande, MA. Toxoplasmosis of the central nervous system in the acquired immunodeficiency syndrome.
N Engl J Med 1992; 327:1643 • Wallace, MR, Rossetti, RJ, Olson, PE. Cats and toxoplasmosis risk in HIV-infected adults. JAMA 1993; 269:76 • Demeter, Lisa. Epidemiology of JC and BK virus infection. In: UpToDate, Rose, BD (Ed), UpToDate, Wellesley,
MA, 2003• Demeter, Lisa. Clinical manifestations and diagnosis of JC, BK, and other polyomavirus infections. In: UpToDate,
Rose, BD (Ed), UpToDate, Wellesley, MA, 2003• Goodman, PC (Ed). The Radiologic Clinics of North America: Imaging of the Patient with AIDS. W.B. Saunders
Co, Philadelphia, PA. 1997.• Klein, RS. Herpes Simplex Type I Encephalitis. In: UpToDate, Rose, BD (Ed), UpToDate, Wellesley, MA, 2003• Guterman KS; Hair LS; Morgello S Epstein-Barr virus and AIDS-related primary central nervous system lymphoma.
Viral detection by immunohistochemistry, RNA in situ hybridization, and polymerase chain reaction. Clin Neuropathol 1996 Mar-Apr;15(2):79-86.
• Antinori A, et al. Diagnosis of AIDS-related focal brain lesions: a decision-making analysis based on clinical and neuroradiologic characteristics combined with polymerase chain reaction assays in CSF. Neurology 1997 Mar;48(3):687-94.
• Doweiko, JP, Groopman, JE. AIDS-related lymphoma: Primary Central Nervous System Lymphoma. In: UpToDate, Rose, BD (Ed), UpToDate, Wellesley, MA, 2003
• Kovacs, JA and Masur, H. Prophylaxis Against Opportunistic Infections in Patients with Human Immunodeficiency Virus Infection. N Engl J Med 2000 May; 342(19); 1416-29
• Gladwin, M and Trattler W. Clinical Microbiology Made Ridiculously Simple. Third Edition. Medmaster Inc. Miami, FL. 2001.