Acta Neuropathologica

, Volume 109, Issue 4, pp 449–455

Fulminant inflammatory leukoencephalopathy associated with HAART-induced immune restoration in AIDS-related progressive multifocal leukoencephalopathy

  • Aurélie Vendrely
  • Boris Bienvenu
  • Jacques Gasnault
  • Jean Baptiste Thiebault
  • Dominique Salmon
  • Françoise Gray
Case Report

DOI: 10.1007/s00401-005-0983-y

Cite this article as:
Vendrely, A., Bienvenu, B., Gasnault, J. et al. Acta Neuropathol (2005) 109: 449. doi:10.1007/s00401-005-0983-y

Abstract

HAART-induced immune restoration is beneficial for patients with AIDS-related progressive multifocal leukoencephalopathy (PML). However, in rare instances, an immune-reconstitution inflammatory syndrome (IRIS) may cause paradoxical clinical deterioration. We report the neuropathological study of an AIDS patient who presented with progressive cognitive deterioration; CD4+ count was 117 and the HIV viral load >104; imaging showed non-enhancing lesions consistent with PML. Following initiation of HAART, CD4+ was 300 and HIV viral load <103, but his neurological symptoms continued to deteriorate. Imaging revealed an increase in the size and number of lesions and enhancement of all the lesions. A stereotactic biopsy showed severe inflammatory and demyelinating lesions with marked infiltration by macrophages and T lymphocytes in the absence of a detectable infectious agent. Despite high doses of steroids, the patient died 3 months after admission. Autopsy showed two types of lesions: (1) active inflammatory PML changes with abundant JC virus, and intraparenchymal and perivascular infiltration by T lymphocytes, and (2) acute perivenous leukoencephalitis devoid of JC virus. Most lymphocytes were CD8+ lymphocytes; CD4+ lymphocytes were virtually absent. Two pathological reactions were associated with the paradoxical clinical deterioration related to dysregulation of the immune response characteristic of IRIS in PML: (1) an accentuation of JCV infection, and (2) a nonspecific acute perivenous leukoencephalitis. We suggest that both these types of lesions are due to an imbalance of CD8+/CD4+ T cells, with massive infiltration of the cerebral parenchyma by CD8+ cytotoxic T lymphocytes in the absence of sufficient CD4+ response. Better understanding of the mechanisms of the IRIS may enable prevention or cure of this severe, sometimes fatal complication of HAART.

Keywords

Progressive multifocal leukoencephalopathyAcquired immunodeficiency syndromeImmune-reconstitution inflammatory syndromeAcute perivenous leukoencephalitisHAART

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Aurélie Vendrely
    • 1
  • Boris Bienvenu
    • 2
  • Jacques Gasnault
    • 3
  • Jean Baptiste Thiebault
    • 4
  • Dominique Salmon
    • 2
  • Françoise Gray
    • 1
  1. 1.Service Central d’Anatomie et de Cytologie PathologiquesAP-HP Hôpital LariboisièreParisFrance
  2. 2.Service de Médecine Interne IIAP-HP Hôpital CochinParisFrance
  3. 3.UF de Suites et de Réadaptation, Service de Médecine Interne, et des Maladies InfectieusesAP-HP Hôpital BicêtreParisFrance
  4. 4.Service de NeurochirurgieFondation Adolphe de RothschildParisFrance