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HIV and the Brain

HIV and the Brain. Chris Farnitano, MD Noon Conference Friday, October 31, 2008. Learning Objectives. -Review the differential diagnosis, workup and treatment of three common presentations of central neurologic disease in AIDS: *Dementia *Headache *focal neuro signs. Forms.

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HIV and the Brain

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  1. HIV and the Brain Chris Farnitano, MD Noon Conference Friday, October 31, 2008

  2. Learning Objectives -Review the differential diagnosis, workup and treatment of three common presentations of central neurologic disease in AIDS: *Dementia *Headache *focal neuro signs

  3. Forms

  4. Case Study #1: R.D. • R.D. is a 44 y.o. male with AIDS • Hx of non-adherence to meds and clinic visits • brought to clinic 2/03 by teenage daughter who has been caring for him

  5. Case Study #1: R.D. • c/o incontinence, increased confusion, trouble walking • requiring help with bathing, dressing, feeding • Sx developed over months • T cells 15, Viral load 16,000 • What could his diagnosis be?

  6. Case Study #1: R.D. • exam shows MMSE 14/30 • CSF: protein 324, glucose 8 • CSF WBC 24: 90% lymphs, 7% monos

  7. CT scan Patient R. D.

  8. Diffuse low attenuation periventricular white matter disease, no mass effect

  9. MRI Patient R.D.

  10. Case Study #1: R.D. • What is no longer in your differential?

  11. Case Study #1: R.D. • Toxo titer neg • India ink prep negative • CSF Smears bacteria, AFB neg • CSF PCR HSV, MTB neg • serum and CSF crypo antigen low titer positive

  12. Case Study #1: R.D. • Diagnosis?

  13. Case Study #1: R.D. • Diagnosis? • Cryptococcal meningitis (CRAG) • Progressive Multifocal Leukencephalopathy (clinical picture, imaging studies) • AIDS dementia complex (clinical picture)

  14. AIDS Dementia Complex • Also known as HIV associated cognitive-motor complex • Occurs in 1/3 of adults with AIDS

  15. AIDS Dementia Complex • Pathogenesis: • Neurons not directly infected • CNS macrophages overrespond to infection with release of neurotoxic substances

  16. AIDS Dementia Complex • process is slowly progressive over months • T cells usually <200 (median = 18)

  17. AIDS Dementia Complex • Symptoms: • 1) Declining mental acuity (difficulty in memory, concentration, mathematical calculations) • 2) Preservation of alertness(even a patient with advanced dementia can be aroused to a level of alertness. This is an important distinction between this and other CNS etiologies

  18. AIDS Dementia Complex • Neuro exam: • non-focal

  19. AIDS Dementia Complex • Neuro exam: Cognition • Early: Inattention, decr. concentration, forgetfulness, slowing of thought processes • Late: Global Dementia

  20. AIDS Dementia Complex • Neuro exam: Motor • Early: Slowed movements, clumsiness, ataxia • Late: paraplegia

  21. AIDS Dementia Complex • Neuro exam: Behavior • Early: apathy, blunting of personality, agitation • Late: mutism

  22. AIDS Dementia Complex • CSF findings • normal vs. mild pleocytosis, incr. Protein • similar to asymptomatic HIV+ individuals

  23. AIDS Dementia Complex • CT/MRI • usually normal in early disease • atrophy can be seen in late disease

  24. HIV Dementia • Note widened sulci and enlarged ventricles

  25. AIDS Dementia Complex • Treatment • Antiviral therapy useful in preventing as well as reversing dementia • importance of CSF penetration of various antivirals not clear • Case P.J. –complete reversal of severe dementia with Combivir

  26. Headache in AIDS • Differential Diagnosis - with any T cell count • medications (especially zidovudine) • aseptic HIV meningitis • bacterial meningitis (usuals plus increased risk of Listeria) • TB meningitis • Syphilitic meningitis - may have focal neuro findings, i.e. cranial nerve palsies

  27. Headache in AIDS • Differential Diagnosis - with any T cell count • bacterial sinusitis - occurs in 1/3 to 2/3 of adults with AIDS • xray: 79% have air fluid level • 60% recur or fail to respond to ABT Rx • refer to ENT for antral puncture and Cx if fail to respond

  28. Headache in AIDS • Differential Diagnosis - with T cells <100 • Above plus Fungal meningitis • most common is Cryptococcus (most have T cells <50) • also consider Coccidiomycosis (Sonoran life zone including all of California Central Valley) and Histoplasmosis (Missisipi Valley and Central America) in endemic areas.

  29. Endemic Areas ForHisto and Cocci

  30. Cryptococcal Meningitis • Sx: • Subacute meningitis w/ fever, HA, malaise • Clinical exam: • Stiff neck in 1/4 • focal neuro exam in 1/5 (often cranial nerve palsy), altered mental status (ie encephalitis) in some • skin lesions resembling molluscum in 3-10%

  31. Cutaneous Cryptococcus • Note similar appearance to molluscum

  32. Cryptococcal Meningitis • Diagnosis: • Serum CRAG >99% positive. Excellent screening test. Not useful for monitoring response to therapy. • CT scan: always do in AIDS patient before LP to rule out mass lesion, given the increased frequency of space occupying lesions in AIDS pts with HA even without focal neuro findings.

  33. Cryptococcal Meningitis • Diagnosis: • LP opening pressure >200 in 60% • Cell counts low (mean 4 lymphs/mm3) • india ink prep positive in 75% • Blood Cx positive in 75% • Serum CRAG positive in 95% • CSF CRAG positive in >90%

  34. Cryptococcal Meningitis • Increase intracranial pressure: • associated with obtundation, cranial nerve palsies, papilledema, blindness and incr. Mortality • 13/14 deaths in one trial with opening pressure (OP)>250 • In observational studies, aggressive management of increased pressure often led to survival without permanent neuro sequellae.

  35. Cryptococcal Meningitis • Increase intracranial pressure: • if opening pressure >300, urgently Rx with drainage of enough CSF to decrease OP by 50% (at least 10-20 ml) • follow up with daily LP drainage until OP normal x 2 days • Consider placement of lumbar drain if OP>400 or daily LP fails to control Sx • No proven benefit to dexamethasone , diamox or mannitol.

  36. Cryptococcal Meningitis • Treatment: • Amphotericin B associated with less mortality than initial treatment with Fluconazone • Adding Flucytosine to Ampho B gave significantly higher rate of CSF sterilization and lower relapse rate than Ampho alone

  37. Cryptococcal Meningitis • Treatment: • Amphotericin B IV and Flucytosine PO x 2 weeks (or until afebrile, HA, N/V resolved) • then Fluconazole 400mg PO qd x 8 weeks • then Fluconazole 200 mg PO qd until Tcells >100 for six months

  38. Cryptococcal Meningitis • Treatment: • If normal mental status, >20 WBC in CSF, and CSF CRAG <1:32, can use fluconazole alone

  39. Cryptococcal Meningitis • Treatment: • High failure rate and high mortality (often weeks after Tx started) in pre-combo antiviral era

  40. Focal Brain Dysfunction in AIDS • Presenting Signs or symptoms: • Focal neuro complaint or exam • New onset seizure

  41. Focal Brain Dysfunction in AIDS • Differential Diagnosis - Abrupt onset: • CVA • TIA

  42. Focal Brain Dysfunction in AIDS • Differential Diagnosis - subacute onset (days): • Toxoplasmosis • Primary CNS lymphoma • Tubercular brain abcess • Cryptococcoma • Varicella encephalitis • CMV • Herpes Simplex Encephalitis

  43. Focal Brain Dysfunction in AIDS • Differential Diagnosis - insidious onset (weeks): • Progressive Multifocal Leucoencephalopathy (PML)

  44. Focal Brain Dysfunction in AIDS • Workup: • CT with and without contrast • MRI • LP if no midline shift or other signs of herniation: send for fungal and AFP smears and Cx, VDRL, cytology, CRAG

  45. Focal Brain Dysfunction in AIDS • Workup: • Serum Toxo IgG • Serum CRAG • CSF for PCR

  46. Toxoplasmosis: • almost all have positive Toxo IgG (this is a reactivation disease) • Toxo acquired from undercooked meat or cysts in cat feces • 15% US adults Toxo IgG+, 50-75% in Europe • In advanced AIDS, if Toxo IgG+ and not on prophylaxis, 12 mo. incidence of Toxo encephalitis is 33% • rare if adherent to Septra prophylaxis

  47. Toxo Encephalitis: 80% have T cells <100 • Clinical: altered MS (70%), focal signs (60%), HA (50%), fever • CT/MRI: multiple ring enhancing lesions

  48. Cerebral Toxoplasmosis • CT with contrast: Note ring enhancement and surrounding edema

  49. Cerebral Toxoplasmosis • Note lesions on medial surface of both hemispheres

  50. Cerebral Toxoplasmosis • Recurrent Sx 6 mo later: CT shows only old calcified lesion

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