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HIV Infection and the CNS

HIV Infection and the CNS . Stephen J. Gluckman, M.D. University of Pennsylvania Botswana-Penn Partnership. Plan. Review features of the major diagnostic possibilities Suggest approach to the patient. Recurring Themes. CSF results are generally not helpful

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HIV Infection and the CNS

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  1. HIV Infection and the CNS Stephen J. Gluckman, M.D. University of Pennsylvania Botswana-Penn Partnership

  2. Plan • Review features of the major diagnostic possibilities • Suggest approach to the patient

  3. Recurring Themes • CSF results are generally not helpful • Imaging studies are rarely diagnostic • Empiric management is often necessary – anywhere in the world

  4. Space Occupying Lesions Toxoplasmosis Lymphoma PML Tuberculoma Cryptococcoma Pyogenic abscess Nocardia CNS Syphilis (gumma) Diffuse Disease Cryptococcal Meningitis Acute Infection HIV Dementia Tuberculous Meningitis CNS Syphilis Toxoplasma encephalitis Cytomegalovirus encephalitis CNS Manifestations of HIV

  5. Two key things to ALWAYS remember in the management of HIV infected patients • HIV infection does not prevent the development of a non-HIV related problem • Opportunistic problems are related to the CD4 (+) cell count. • If the count is > 200-300, the problem is probably not related to the HIV infection.

  6. Space Occupying Lesions

  7. Toxoplasmosis • The most common in the west of the CNS space occupying lesions in a person with a CD4 count <200 (usually < 100) • Prevalence of toxoplasma CNS disease is unknown in Botswana • Seroprevalence is low • Reactivation disease • Cat feces • Meat • Presentation is typically sub acute and focal • May be seizures • Multiple ring enhancing lesions • 1/3 single lesion • CSF is normal or non-specific

  8. Toxoplasmosis • Other than a biopsy there is no good diagnostic test • Antibody testing is very non-specific and occasionally insensitive • Usual “diagnostic” test is response to Rx • Expect response to treatment in 2 weeks

  9. Toxoplasmosis • Things that make toxo unlikely • Negative toxo serology • Patient taking Co-trimoxazole prophylaxis • CD4 count > 100 • Treatment • Pyrimethamine (50-100 mg QD) plus leucovorin and Sulfadiazine (1 gm QID) • Alternatives • Fansidar 2-3 daily • Atovoquone 750 mg QID • Azithromycin 1200 mg QD • Clindamycin 600 QID • Co-trimoxazole 10mg/kg/day of trimethoprim • Dapsone 100 mg QD

  10. Primary CNS Lymphoma • Subacute and focal • CD4 count typically <50 • Single ring enhancing lesion is more common than toxoplasmosis • Associated with EBV infection • CSF is normal or non-specific • CSF cytology is negative • 90% are PCR (+) on CSF for EBV • Diagnosis by biopsy

  11. PML • Reactivation of JC virus (Papova virus) • CD4 counts typically <100 • Subacute evolution of focal disease • CSF usually normal • “Diagnostic” CT appearance: Subcortical white matter disease without evidence of inflammation or edema • Diagnosis: PCR on CSF for JCV (90%)

  12. Tuberculoma • Presents like any other mass lesion • CT appearance • Looks like an abscess or a tumor • Nothing characteristic about CT appearance • May be ring enhancing • CSF • Non-specifically abnormal or completely normal • Diagnosis: brain biopsy • Treatment: standard drugs though the duration has not been studied • Many people treat longer than pulmonary TB

  13. Pyogenic Brain Abscess • Presents like a mass rather than like infection • May not have fever • CT • Ring enhancing lesion(s) • CSF • Non-specifically abnormal

  14. Pyogenic Brain Abscess • Microbiology • Depends upon the underlying cause • Sinusitis or otitis or mastoiditis or dental: mixed organisms • Bronchiectasis or lung abscess or empyema: mixed organisms • Paradoxical embolus: single organism • Endocarditis: single organism usually Staphylococcus aureus • About 30% do not have an underlying cause. • These tend to have multiple organisms so are presumed to come form sub-clinical sinus, ear, or pulmonary source

  15. Pyogenic Brain Abscess • Diagnosis • Brain aspirate or biopsy to prove abscess and obtain proper microbiology • Anti-microbiol management • If known single bacterium: treat the bug • If mixed or presumed mixed focus • Chloramphenicol 50 mg/kg/day in 4 divided doses OR • Cefotaxime 2 gm Q4H and metronidazole 500 mg Q6H • Treat for several months until CT scan is normal or looks inactive

  16. Nocardia • Nocardia brain abscess • Presents like other brain abscesses, but some predisposition to involve the brain stem • Can only be diagnosed by biopsy • Often diagnosed presumptively by finding nocardia elsewhere • Treatment • Initial • Cefotaxime 2 gm Q6H and Amikacin 7.5mg/kg Q12H or • Co-trimoxazole15 mg/kg/day IV x 3-6 weeks • Continuation • Co-trimoxazole 480/2400 BD PO x 6-12 months

  17. Syphilis(gumma) • Rare manifestation • Presents as a mass • Looks like a brain tumor • Diagnosis suggested by positive serology • Diagnosis proven by biopsy • Treatment • Pen G 18-24 million units/day x 14 days

  18. NON-FOCAL CNS DISEASE

  19. Cryptococcal Meningitis • Clinical Presentations • Typical • Subacute onset of fever and headache • Photophobia and/or meningeal signs in only 25% • Less typical • Seizures • Confusion • Progressive dementia • Visual or hearing impairment • FUO • Diagnosis • Very rare if CD 4 (+) cell count is > 100 • CSF: may be deceptively normal • Serum CRAG: > 99% sensitive in AIDS patients

  20. Cryptococcal Meningitis • In 2003 there were 193 (+) CSF cultures for cryptococcus from PMH * • Leucocytes • No leucocytes in 31% • Only 1-10 leucocytes in 23% • 7% had > 250 leucocytes • 30% of these had predominately PMN’s • 95% (+) India Ink • 1% (-) cryptococcal antigen *Bisson et al

  21. Treatment**Modified IDSA Guidelines • Immunosuppressed (pulmonary, cutaneous, or meningitis) • Induction • Amphotericin B 0.7-1 mg/kg/day plus 5-flucytosine 100mg/kg/day x 2 weeks then • Consolidation • Fluconazole 400 mg/day x 6-10 weeks then • Suppression • Fluconazole 200 mg/day x ?

  22. Cryptococcal MeningitisTreatmentOne More Thing • Anti-fungal: induction, consolidation, maintenance • Pressure management • Elevated pressure • 75% > 200 • 25% > 350 • Repeated lumbar punctures • Increased pressure: daily until normal x several days • Normal pressure: recheck at 2 weeks prior to switching to fluconazole • Lumbar drain • VP shunt: if still elevated at 1 month • No role for • acetazolamide, mannitol • Steroids: ?

  23. Acute HIV Infection • Aseptic Meningitis • Indistinguishable from other causes of aseptic meningitis unless associated with the other features of the acute syndrome • Adenopathy • Rash • Pharyngitis • Encephalitis • Needs to be considered in the differential diagnosis of acute encephalitis • Remember as with other manifestations of the acute infection HIV antibody may be negative. So consider: • Seroconversion • PCR • P24 antigen

  24. HIV Dementia • Diagnosis of exclusion that is supported by • Atrophy on CT scan • CSF normal or elevated protein • Typical feature is withdrawn appearance but can be anything • Can have a dramatic response to ARV’s

  25. Tuberculous Meningitis • Similar presentation to cryptococcal meningitis, though can be a bit more acute • Diagnosis made by CSF, but insensitive • Typically lymphocytic predominance, but may have PMN’s early • Moderate low glucose • AFB smear (+) in 5% • Culture (+) in 50% • Usually “diagnosed” by finding a sub-acute onset lymphocytic meningitis that is cryptococus and cytology negative. • Treatment the same as pulmonary TB

  26. CNS Syphilis • Secondary • Aseptic meningitis • Tertiary • Meningovascular • General Paresis • Tabes Dorsalis • Asymptomatic neurosyphilis

  27. Toxoplasma encephalitis • Toxoplasma may occasionally present as diffuse CNS disease rather than an abscess • CMV encephalitis • Relatively rare • Diagnosed by PCR on CSF, NOT BY SEROLOGY

  28. Glucose Calcium Sodium Blood Gas Drugs India Ink Cryptococcal Ag Cytology TB culture Routine Culture

  29. Approach to Patient(cont)

  30. Approach to the Patient • Try to avoid the use of steroids because the “diagnostic” test is response to therapy • If there is significant neurological deficit and/or concerns about herniation then • Have no choice but to use steroids • May want to treat for several things • If a brain biopsy is not obtainable

  31. Recurring Themes • As with all problems in HIV patients the differential diagnosis is CD 4 count dependent • As with all problems in HIV patients we must never forget to consider non-HIV related explanations for the symptoms • CSF results are generally not helpful • Cryptococcus is an exception • Imaging studies are rarely diagnostic • PML is an exception • Empiric management is often necessary – anywhere in the world

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