PMID- 15739098
OWN - NLM
STAT- MEDLINE
DCOM- 20050901
LR  - 20071109
IS  - 0001-6322 (Print)
IS  - 0001-6322 (Linking)
VI  - 109
IP  - 4
DP  - 2005 Apr
TI  - Fulminant inflammatory leukoencephalopathy associated with HAART-induced immune 
      restoration in AIDS-related progressive multifocal leukoencephalopathy.
PG  - 449-55
AB  - 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 >10(4); imaging showed non-enhancing lesions consistent with PML. 
      Following initiation of HAART, CD4(+) was 300 and HIV viral load <10(3), 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.
FAU - Vendrely, Aurelie
AU  - Vendrely A
AD  - Service Central d'Anatomie et de Cytologie Pathologiques, AP-HP Hopital 
      Lariboisiere, 2 rue Ambroise Pare, 75475 Paris, France.
FAU - Bienvenu, Boris
AU  - Bienvenu B
FAU - Gasnault, Jacques
AU  - Gasnault J
FAU - Thiebault, Jean Baptiste
AU  - Thiebault JB
FAU - Salmon, Dominique
AU  - Salmon D
FAU - Gray, Francoise
AU  - Gray F
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050301
PL  - Germany
TA  - Acta Neuropathol
JT  - Acta neuropathologica
JID - 0412041
RN  - 0 (Antigens, CD)
SB  - IM
MH  - Acquired Immunodeficiency Syndrome/complications/*immunology/pathology/therapy
MH  - Antigens, CD/metabolism
MH  - Antiretroviral Therapy, Highly Active
MH  - CD4 Lymphocyte Count/methods
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Disease Progression
MH  - Humans
MH  - Immunohistochemistry
MH  - JC Virus/physiology
MH  - Leukoencephalopathy, Progressive 
      Multifocal/complications/*immunology/pathology/therapy
MH  - Magnetic Resonance Imaging/methods
MH  - Male
MH  - Viral Load/methods
EDAT- 2005/03/02 09:00
MHDA- 2005/09/02 09:00
CRDT- 2005/03/02 09:00
PHST- 2004/11/10 00:00 [received]
PHST- 2004/12/22 00:00 [accepted]
PHST- 2004/12/22 00:00 [revised]
PHST- 2005/03/02 09:00 [pubmed]
PHST- 2005/09/02 09:00 [medline]
PHST- 2005/03/02 09:00 [entrez]
AID - 10.1007/s00401-005-0983-y [doi]
PST - ppublish
SO  - Acta Neuropathol. 2005 Apr;109(4):449-55. doi: 10.1007/s00401-005-0983-y. Epub 
      2005 Mar 1.