Human immunodeficiency virus encephalitis is the pathological correlate of dementia in acquired immunodeficiency syndrome.

While dementia has been observed in approximately one-fourth of terminally ill patients with acquired immunodeficiency syndrome, it has been difficult to attribute this clinical disorder to a single neuropathological substrate. We used a simple and readily reproducible scale for estimating the burden of human immunodeficiency virus (HIV) in the central nervous system (i.e., severity of HIV encephalitis) and compared this to autopsy neurological summaries of dementia. Like others, we found that multinucleated giant cells were present in only half of the dementia patients. However, all of the dementia patients had severe HIV encephalitis as assessed by measurements of intra-central nervous system viral burden. Additional patients had severe HIV encephalitis without clinical histories of dementia. We interpret these latter findings as evidence that HIV encephalitis exists for a period of time before the clinical symptomatology develops. Comparison of presence or absence of concurrent cytomegalovirus encephalitis showed no association with dementia.

Skeletal muscle involvement in tropical spastic paraparesis/HTLV-1-associated myelopathy.

The frequency of muscle involvement in TSP/HAM is not known, nor is the precise role that HTLV-1 and the diverse cytokines play in the genesis of HTLV-1-associated diseases. In order to better define the frequency and characteristics of the skeletal muscle involvement in TSP/HAM, we studied 11 affected patients. EMG was performed in 9 patients and muscle biopsy was performed in all 11. Muscle tissue was analyzed using: reverse transcriptase PCR for interleukin-1 in 8; PCR for HTLV-1 proviral DNA in 5; and electron microscopy for viral particles in 3. We found pathologic alterations in all 11 patients. Four patients (36%) had a neurogenic process, while a primary muscle involvement was observed in the rest (64%). Four patients (36%) had polymyositis, and 3 (27%) had a noninflammatory myopathy. Muscle weakness in the upper limbs was significantly associated with inflammation in the muscle biopsy. EMG was abnormal in only 2 of 9 patients. Reverse transcriptase PCR did not demonstrate message for interleukin-1 in any sample examined. PCR did identify HTLV-1 proviral DNA in the muscle of 3 patients. Retroviral-like particles were found, by EM, in only one biopsy. HTLV-1 may play an important role in the pathogenesis of the frequent myopathies associated with HAM/TSP.

In vivo model of HIV infection of the human brain.

Approximately one quarter of the AIDS patients have severe HIV encephalitis with diffuse neuronal damage that may be mediated by immune factors secreted by CNS macrophages. Based on an in vitro brain microsphere model, we developed an in vivo system in which human embryonic brain tissue survives for several months in the interscapular fat pad of SCID mice. Coculture of human brain tissue with macrophages prior to transplantation resulted in infiltration of the microspheres by activated macrophages. When the macrophages were infected in vitro with a neurotropic HIV strain, viral particles were detected in vivo up to 3 months after transplantation. HIV-infected transplants contained multinucleated giant cells similar to those seen in HIV encephalitis. However, the neuroglial component degenerated in the fat pad of SCID mice. The absence of synaptogenesis in the human transplants suggests that the murine fat pad lacks adequate stimuli or support for human neuronal differentiation. To study neurologic damage associated with HIV infection, sites of implantation that stimulate synaptogenesis (e.g. murine CNS) will need to be explored. Based on these findings we conclude that transplantation of brain microspheres with HIV-infected macrophages into SCID mice may be an achievable model of HIV encephalitis.