opportunistic infections of the cns in patients with aids

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?


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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


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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?


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Portable CXRPortable CXR

No evidence of consolidation or active infection

Image from BIDMC PACS


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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


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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


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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


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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


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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


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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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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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•• >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


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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


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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



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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


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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


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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



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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.

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