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

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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.

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Acknowledgements

Supported by grants to Dr. Gray from Agence Nationale de Recherches sur le SIDA (ANRS) and Ensemble Contre le SIDA (ECS). The authors wish to thank Dr. Catherine Keohane for kindly reviewing the English, Dr. Patrice LeFloch-Progent in the Service Central d’Anatomie et Cytologie Pathologiques at Hôpital Cochin (Pr. M.C. Vacher-Lavenu) who performed the autopsy, and Marie-Annick Bretel, Patrice Castagnet, Katia Dossou, Isabelle Levesque and Claudine Poron, for histological preparations.

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Authors and Affiliations

  1. Service Central d’Anatomie et de Cytologie Pathologiques, AP-HP Hôpital Lariboisière, 2 rue Ambroise Paré, 75475, Paris, France

    Aurélie Vendrely & Françoise Gray

  2. Service de Médecine Interne II, AP-HP Hôpital Cochin, Paris, France

    Boris Bienvenu & Dominique Salmon

  3. UF de Suites et de Réadaptation, Service de Médecine Interne, et des Maladies Infectieuses, AP-HP Hôpital Bicêtre, Paris, France

    Jacques Gasnault

  4. Service de Neurochirurgie, Fondation Adolphe de Rothschild, Paris, France

    Jean Baptiste Thiebault

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  1. Aurélie Vendrely
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Correspondence to Françoise Gray.

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Vendrely, A., Bienvenu, B., Gasnault, J. et al. Fulminant inflammatory leukoencephalopathy associated with HAART-induced immune restoration in AIDS-related progressive multifocal leukoencephalopathy. Acta Neuropathol 109, 449–455 (2005). https://doi.org/10.1007/s00401-005-0983-y

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