Vacuolar myelopathy with multinucleated giant cells in the acquired immune deficiency syndrome (AIDS)

Abstract

Vacuolar myelopathy (VM) is a frequent neurological complication of the acquired immune deficiency syndrome (AIDS). A suspected connection between VM and human immunodeficiency virus (HIV) has been based only on HIV isolation from affected spinal cord tissue. We report here an AIDS patient dying after 14 months of progressive dementia, including 3 months of spinal signs and symptoms. At autopsy, the brain revealed moderate diffuse damage of the white matter compatible with HIV-induced progressive diffuse leukoencephalopathy. The spinal cord showed VM mainly in the lateral and the posterior columns. Mono- and multinucleated macrophages were localized within intramyelinic and periaxonal vacuoles. Light and electron microscopic immunocytochemistry revealed the presence of HIV antigens restricted to mono- and multinucleated macrophages within the spongy lesions. Productive HIV infection is documented for the first time within VM lesions of this case. Therefore, VM should be included among HIV-induced lesions of the central nervous system. The intimate relation of infected macrophages to vacuolar myelinopathy could suggest secretion of a myelinotoxic factor by macrophages productively infected by HIV. Immune electron microscopy appears as promising tool to detect HIV in tissue even when the density of virus may be low.

Diffusion tensor MR imaging (DTI) metrics in the cervical spinal cord in asymptomatic HIV-positive patients

“…Pathologically, the disease is usually more severe in the mid-thoracic region than in the cervical spinal cord [20, 21]. Most published series on VM describe a predominant involvement of the lateral and posterior columns of the spinal cord [20, 22]; however, in a pathologic study on 20 patients with VM, no significant longitudinal gradient was found in score severity in the posterior, lateral, or anterior columns [21]. Vacuoles are the result of edematous swelling within myelin, with splitting of the lamellae.…”

Human immunodeficiency virus type 1 expression in the central nervous system correlates directly with extent of disease.

“…Both methods showed that the frequency of infected cells in peripheral blood is much higher in individuals with AIDS than in those who are asymptomatic and seropositive, suggesting that HIV-1 infection of such cells contributes to CD4+ cell depletion in patients with AIDS. Studies of HIV-1 infection in vivo have demonstrated virus in organs showing tissue damage, particularly the CNS (2-16) and lung (33,34 Four of the previous studies identifying HIV-1 in spinal cords found the virus associated with the lesions of vacuolar myelopathy (2,(10)(11)(12)(13), but not all did (6,8,14,15); we believe this disparity most likely stems from differences in the specific methods used to detect HIV-1 and the pathology of the samples. For example, our procedure for in situ hybridization included autoradiograpic exposure for a period of 10-24 days in various experiments, while another study employing in situ hybridization (15) exposed spinal cord specimens for 2-3 days.…”

“…These data support a role for HIV-1 in the pathogenesis of tissue damage and related clinical disease in infected individuals. (4)(5)(6)(11)(12)(13), with evidence for infection of the astrocyte, oligodendrocyte, endothelial cell, and neuron reported as well (5,6,10). We used in situ hybridization to further investigate HIV-1 pathogenesis in the CNS by studying spinal cords from AIDS patients with a broad range ofcord pathology.…”

“…HIV-1 has been demonstrated in the brain and spinal cord of AIDS patients with neurological disease by using a variety of techniques (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16), and high levels of unintegrated viral DNA in brain tissue were found to be correlated with the presence of HIV-1 encephalitis (16). Viral expression in the central nervous system (CNS) has been localized primarily to the macrophage (4)(5)(6)(11)(12)(13), with evidence for infection of the astrocyte, oligodendrocyte, endothelial cell, and neuron reported as well (5,6,10).…”

HIV-1 Infection of the Central Nervous System

“…VM is characterized by numerous vacuolar myelin swellings and macrophages in multiple areas of the spinal cord (31,71,(158)(159)(160)(161)(162)(163). VM predominantly involves the dorsolateral spinal tracts (Fig.…”