Journal of neuro-AIDS最新文献

Two patients with HIV-1 infection associated with neurological complications were repeatedly followed with cerebrospinal fluid (CSF) and serum analyses before, and 1 to 2.5 years after single zidovudine treatment. Retrospectively, HIV-RNA levels were analyzed with quantitative PCR assay. The number of HIV-RNA copies in CSF was decreased already 1 week after initiation of zidovudine, and continued to decrease during 5 months of follow up, while the serum levels increased during the same period. The difference between HIV levels in CSF and serum compartments following zidovudine treatment indicates that the CSF viral load does not merely reflect blood levels. Single zidovudine treatment did not reduce the viral load in CSF to non-detectable levels but had a better and more long-lasting anti-HIV effect in CSF than in peripheral blood.

In the absence of significant neuronal infection HIV induces neuronal damage and death. The pathogenesis of this process is not clear and can only be assessed in the HIV infected brain by examining surviving neuronal populations. Cerebellar Purkinje cells are a model population. We have already demonstrated glutamate receptor alterations in these neurons in AIDS, and in the current study we have investigated the phosphorylation status of heavy neurofilament (NF-H), which is under the control of various intracellular kinases. While the number of Purkinje cells expressing non-phosphorylated NF-H was unchanged, the number of Purkinje cells expressing phosphorylated NF-H was decreased by 36% in the HIV group. This may be a marker of neuronal damage, and possibly indicate alteration in the activity of various intracellular signalling kinase pathways in the HIV infected brain.

gp120 induction of the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) was studied in cultures of purified astrocytes. Incubation of pure mouse cortical astrocytes with gp120 IIIB induced the expression of TNF-alpha mRNA, assessed by in situ hybridization. Anti- TNF-alpha immunocytochemical staining of gp120 IIIB stimulated astrocytes indicated the presence of TNF-alpha. gp120 IIIB treatment also stimulated secretion of bioactive TNF-alpha from astrocytes, which was prevented by inhibitors of transcription and translation. Hippocampal and cerebellar astrocytes displayed similar behaviors. Further, gp120 displayed cytotoxicity for astrocytes that depended on macromolecular synthesis. The data are the first to show gp120 IIIB induction of de novo TNF-alpha production by pure astrocytes. Because TNF-alpha exerts a wide array of effects in the brain of infected individuals and has HIV-1 inducing activity as well, induction of this cytokine by gp120 IIIB in astrocytes may contribute importantly to the pathogenesis of AIDS dementia complex. Since TNF-alpha can stimulate astrocyte reactivity and proliferation by an autocrine mechanism, the extent of the gp120 effect could conceivably increase with HIV-1 disease progression in a self-amplifying loop, involving other cell types, thus favoring both virus persistence and a chronic disease state.

We report two young adults with the acquired immunodeficiency syndrome (AIDS), one who presented with multiple ischemic cerebral infarctions and the other who presented with multiple episodes of transient neurologic deficit. Both patients had pulmonary hypertension and a patent foramen ovale (PFO) by echocardiogram. To our knowledge, this is the first report describing HIV-associated pulmonary hypertension and PFO in HIV infected patients with presumed embolic cerebrovascular disease.

The excitotoxic amino acid glutamate, which is elevated in blood and cerebrospinal fluid from subjects with AIDS dementia complex, is crucially implicated in the neurotoxicity of HIV infection. We describe a subject with AIDS dementia complex who showed a significant motor and cognitive improvement after a course of intravenous acetylcarnitine therapy. The clinical improvement was paralleled by a significant reduction of glutamate concentrations in both blood and cerebrospinal fluid. A prospective pilot study confirmed that acetylcarnitine administration resulted indeed to reduce the blood levels of glutamate in AIDS patients treated with acetylcarnitine therapy in order to prevent the neurotoxicity of nucleoside analogs. Even though the mechanisms responsible for the reduction of glutamate concentrations remain to be established, we suggest that acetylcarnitine should be added to the list of drugs under investigation for the treatment of AIDS dementia complex. The anti-apoptotic activity of carnitines and their safety profile further support this view.

In the CNS, HIV-1 causes cognitive motor complex (CMC) in about 30-40% of patients. To explain CMC physiopathology: disequilibrium of cytokine networks, calcium influx, free radicals and toxic effects by HIV-1 have been evoked. Neurotropic mutants have not been unambiguously proven nor 'variants' of HIV-1 with biological properties that could cause CMC. By computerized analysis of gp120 C2-V3 subtype B sequences from retroviral databases, and applying stringent criteria, we found: (i) mutations specific for CMC; (ii) mutations associated with the absence of CMC (N-CMC); (iii) mutations with specificity for the geographical region of origin, and finally (iv) shared mutations representing 'hot spots.' We suggest that the capability to cause or not to cause CMC may be present in the virus prior to infection. In the future, these markers could be used to guide treatments with novel neuroprotective regimes.

Purpose: Analyze the value of TL-201 (Tl) brain single-photon emission computed tomography (SPECT), to differentiate CNS lymphoma from toxoplasmosis in AIDS patients.

Material and methods: Twenty-four AIDS patients with MR enhancing lesion(s), underwent a brain Tl SPECT. Final diagnosis was established by pathology and clinical/MR follow-up.

Results: Nine patients had CNS tumor, 9 toxoplasmosis and 6 other non-tumorous lesions. The sensitivity of T1 to diagnose CNS tumor was 77% and the specificity 93%. Two false negative studies correspond to tumors with significant necrosis.

Conclusions: T1 proved useful for differentiating brain neoplasm from toxoplasmosis. Tumors with significant necrosis, did not show the expected increase in T1 uptake. Determination of T1 uptake ratios help detect tumor with faint tracer uptake.

Brains of macaques inoculated with macrophage-tropic, neurovirulent virus 7F, with lymphocyte-tropic SIV mac239, or with dual-tropic SIVmac239/1yE, were examined for microglial activation, astrocyte activation, apoptosis and neuron loss. The brain one animal inoculated with neurovirulent virus 7f showed massive microglial activation as assessed by expression of the major histo-compatibility complex class II (MHC-II). In this animal very numerous, large microglial nodules expressing MHC-II were concentrated in the basal pons and internal capsule. These microglial nodules contained cells undergoing apoptosis detected by in situ end labeling of fragmented DNA. In this animal, neuron loss was apparent near the microglial nodules. In the animals inoculated with SIVmac239 or SIVmac239/17E, pathologic changes such as perivascular cuffing and formation of microglial nodules were absent. However, increased expression of MHC-11 by microglial cells was also concentrated in white matter of the basal pons, midbrain and internal capsule. These results indicate the microglial activation in SIV-infected macaques follows a ventral to dorsal gradient regardless of viral tropism. These results also show that the type and severity of neuropathological changes in SIV-infected macaques is highly dependent on the tropism of the inoculated virus.

The purpose of this study was to determine whether short echo-time proton magnetic resonance spectroscopy (H-MRS) could detect mobile lipid resonances attributable to myelin breakdown products in the deep cerebral white matter of patients with AIDS who have severe diffuse/patchy white matter hyperintensity on T2-weighted magnetic resonance imaging (MRI). Seven patients with AIDS and clinical HIV-associated dementia complex (HADC) and 12 male controls were studied at 1.5T using a single 8 ml voxel, gradient localised, stimulated echo acquisition mode (STEAM) spectroscopy sequence. Spectra were acquired at an echo time of 20 ms with a repetition time of 5000 ms. No spectroscopic peaks were identified at 0.9 ppm and 1.3 ppm (corresponding to lipid resonances) in 6 of the 7 patients with AIDS or in any of the controls. Lipid resonances were identified in 1 patient who had been taking anti-retroviral therapy for 8 weeks. Follow up MRI/H-MRS, performed after a further 14 weeks of anti-retroviral therapy, showed partial resolution of white matter hyperintensity and lipid resonances were not detectable. These data suggest that mobile lipids are only rarely detected by H-MRS in patients with HADC and abnormalities on MRI and that their presence may be transitory.