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2011 Diagnostic Slide Session Case 7

2011 Diagnostic Slide Session Case 7. Aditya Raghunathan Suzanne Z. Powell. Presentation. 47 year old woman Altered mental status HIV diagnosed in 1993 NOT taken therapy ~ 14 yrs Past medical history: Shingles On admission: CD4 20 cells/ μ L Mediastinal mass. MRI. T2. FLAIR.

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2011 Diagnostic Slide Session Case 7

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  1. 2011 Diagnostic Slide SessionCase 7 Aditya Raghunathan Suzanne Z. Powell

  2. Presentation 47 year old woman • Altered mental status • HIV diagnosed in 1993 NOT taken therapy ~ 14 yrs • Past medical history: Shingles • On admission: CD4 20 cells/ μL Mediastinal mass

  3. MRI T2 FLAIR

  4. Mediastinal Mass Adenomatous hyperplasia (Multinodular goiter)

  5. Subsequently, frontal lobe lesions were biopsied...

  6. Intra-Operative Cytology

  7. DIAGNOSIS?

  8. LFB-PAS

  9. GFAP

  10. Additional Studies • HSV 1, HSV2, CMV, EBV, Enterovirus IHC & culture : Negative • BK virus IHC, JC virus-ISH: Negative • Toxoplasma IHC: Negative • Bacterial/ fungal stains & cultures: Negative

  11. HHV3 (VZV) Immunostain

  12. Electron Microscopy

  13. VZV Immunostain positive • PCR: VZV DNA detected • Measles IHC/ PCR: Negative

  14. Human herpes virus 3 encephalitis/vasculopathy (HHV3, Varicella zoster virus) • In the context of an HIV+ patient, untreated for 14 years

  15. HIV in the HAART Era • Epidemiologically ↓ “main” opportunistic inf.e.g. Toxoplasmosis, Cryptococcal meningitis • ↑ Nonspecific/ nonlethal CNS diseases • ↑ Uncommon CNS infections • VZV & HSV Gray F et al. (2003)

  16. CNS Symptoms & CSF VZV Load • Immunocompromised: Deeper sites • Small-vessel vasculopathy, meningoencephalitis, ventriculitis & myelitis • 97 cases: ↑ CSF VZV DNA load in encephalitis & acute aseptic meningitis • > Cranial nerve disease Kleinschmidt-DeMasters BK et al. (2001) Persson A et al. (2009)

  17. VZV Detection • Highly cell associated • Present in low titers • Culture from CSF rarely + • In CSF, diagnostic value of detecting anti-VZV IgG antibodies >VZV DNA Nagel et al. (2007)

  18. VZV Genotypes • 4021 patients w. ? CNS VZV infection • 43 + VZV DNA in CSF by PCR • CNS disease frequently w/o rash • Can resemble HSV encephalitis • 7 genotypes identified at CDC • 1 Oka vaccine strain  ? Vaccine - associated CNS disease Pahlud et al. (2011)

  19. References • Pahud BA, Glaser CA, Dekker CL, Arvin AM, Schmid DS. Varicella zoster disease of the central nervous system: epidemiological, clinical, and laboratory features 10 years after the introduction of the varicella vaccine. J Infect Dis. 2011 Feb 1;203(3):316-23. • Gray F, Chrétien F, Vallat-Decouvelaere AV, Scaravilli F. The changing pattern of HIV neuropathology in the HAART era. J Neuropathol Exp Neurol. 2003 May;62(5):429-40. • Kleinschmidt-DeMasters BK, Gilden DH. Varicella-Zoster virus infections of the nervous system: clinical and pathologic correlates. Arch Pathol Lab Med. 2001;125:770-80 • Nagel MA, Forghani B, Mahalingam R, et al.: The value of detecting anti-VZV IgG antibody in CSF to diagnose VZV vasculopathy. Neurology 2007, 68:1069–1073. • Persson A, Bergström T, Lindh M, Namvar L, Studahl M. Varicella-zoster virus CNS disease--viral load, clinical manifestations and sequels. J Clin Virol. 2009 Nov;46(3):249-53.

  20. Thank You!

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