PubMed Health⌕ Search

Biomedical subjects

S V Tan

Publications and source records attributed to S V Tan.

8 recordsLinked to original sources
PubMed1998

Hypothesis on the pathogenesis of vacuolar myelopathy, dementia, and peripheral neuropathy in AIDS.

Certain aspects of the clinical syndrome of dementia, cerebral atrophy, predominantly sensory neuropathy, and vacuolar myelopathy in AIDS resemble those seen in vitamin B12 deficiency. Pathologically, there are similarities not only in the changes in the spinal cord, but also in the brain and peripheral nerves. The pathogenesis of vacuolar myelopathy may be secondary to a combination of immune mediated myelin and oligodendrocyte injury, and simultaneous impairment of repair mechanisms due to a deficiency of S-adenosylmethionine (SAM). Products derived from macrophages may interfere directly with the methyl transfer cycle through the generation of reactive oxygen intermediates and reactions involving nitric oxide and peroxynitrite which may limit the supply of methionine for conversion to SAM, both by direct interaction as well as through inhibition of methionine synthase. Macrophage activation with secretion of cytokines and other biologically reactive substances within the nervous system is sustained in the late stages of HIV infection by the general effects of immune depletion, including loss of T cells (with concomitant reduction of macrophage regulatory molecules) and recurrent opportunistic infections, and may be further augmented by the local presence of the virus itself (or its surface glycoprotein gp120). This would account for the common, but not exclusive, occurrence of vacuolar myelopathy in AIDS. The ability of the virus and its products to stimulate macrophage and microglial activation may also explain the association between severity of vacuolar myelopathy and the presence of HIV encephalitis. A similar mechanism may underlie the pathogenesis of dementia, cerebral atrophy, and peripheral neuropathy. Local factors or differential susceptibility between the central and peripheral nervous system may determine whether myelinotoxic or neurotoxic processes predominate; the prominence of myelin involvement in the spinal cord, and axonal involvement peripherally may reflect both ends of this range, with the brain manifesting a more equal balance of both processes.

AIDS Dementia Complex↗
PubMed1996

AIDS-associated vacuolar myelopathy and tumor necrosis factor-alpha (TNF alpha).

The spinal cords from 15 patients with AIDS-associated vacuolar myelopathy (VM), 4 AIDS patients without VM, and 5 HIV-seronegative controls, were studied with immunocytochemistry for TNF alpha. CSF and blood from HIV-seropositive patients with VM (n = 16), non-vacuolar myelopathies (n = 8), CNS infection but no clinical myelopathy (n = 31), no clinical or radiological evidence of CNS disease (n = 9), and from 7 HIV-seronegative controls with motor neurone disease were assayed for TNF alpha using an ELISA technique. TNF alpha was present on immunostaining in all the 15 cords with VM studied. The stained cells were macrophages, microglia and endothelial cells. The amount of immunostaining was higher in cords with VM compared with cords from HIV-seropositive patients without VM (p = 0.001). The distribution of staining corresponded to the areas of pathology but did not correlate with the severity of the VM. Immunostaining was also higher in the HIV-seropositive group compared to the HIV-seronegative controls (p = 0.001). There was no significant difference in the levels of TNF alpha in the CSF of patients with VM compared to any of the other groups studied. Blood levels of TNF alpha were lower in the HIV-seropositive controls without CNS disease and in the HIV-seronegative MND controls, than in patients with VM, non-vacuolar myelopathies, and CNS disease. CSF TNF alpha levels did not appear to be a reliable indicator of intramedullary levels. The findings support the hypothesis that TNF alpha may be relevant in the pathogenesis of vacuolar change in VM.

Acquired Immunodeficiency Syndrome↗
PubMed1995

AIDS-associated vacuolar myelopathy. A morphometric study.

The post-mortem pathology in 20 spinal cords of human immunodeficiency virus (HIV) infected patients with vacuolar myelopathy was quantified by evaluating (i) the intensity of myelin change, vacuolation and macrophage density; and (ii) the areas of white matter covered by each feature. Severity scores were constructed for (i) the anterior, lateral, and posterior white matter columns; (ii) each level of spinal cord; and (iii) the whole spinal cord [Cord Total and Cord Average Severity Scores (CTSS, CASS)]. Astroglial activation was scored separately. In 14 cords with mild-moderate vacuolar myelopathy (CASS = 23-259), macrophages were the most prominent pathological feature, and level severity scores were higher at mid-thoracic than cervical levels (P = 0.009). In six cords with severe vacuolar myelopathy (CASS = 396-614), vacuolation, demyelination and macrophages were equally evident and thoracic and cervical level severity scores were similar. The most severe lesions showed evidence of clearing of macrophages from the collapsed centres. A clinical lower limb score correlated with the anterior (P = 0.03) and lateral (P = 0.04) column total scores and with the CTSS (P = 0.04) in the nine patients who had had both myelopathy related disability and all cord levels available. There was no significant longitudinal gradient in score severity in the posterior, lateral or anterior columns and no evidence of a dying-back phenomenon. There was no evidence of Wallerian degeneration occurring as a primary process. Astroglial activation did not correlate with the severity or duration of the vacuolar myelopathy. Detection of HIV p24 antigen in the spinal cord related to the local presence of multinucleated giant cells and to antigen expression in the brain but not with the severity of vacuolar myelopathy. The pathology in vacuolar myelopathy appeared to start in the mid-low thoracic cord, with increasing rostral involvement as the disease became more severe. The relative prominence of macrophages in mild-moderate lesions suggests they may be involved early in the pathogenesis of vacuolar myelopathy.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Herpes simplex type 1 encephalitis in acquired immunodeficiency syndrome.

A severe acute necrotizing herpes simplex virus type 1 encephalitis, apparently mediated by macrophages or cytokines or both, was seen in a patient with acquired immunodeficiency syndrome. The necrosis had a distribution similar to that seen in immunocompetent subjects. Viral inclusions were abundant and meningeal reaction was minimal, as previously described in one anergic patient.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Central nervous system opportunistic infections in HIV disease: clinical aspects.

Nervous system opportunistic infections are seen in about one fifth of AIDS cases and account for over 40% of the patients with neurological manifestations. Serious infections are seen in severely immunosuppressed patients, usually with CD4 counts of 200 ml-1 or less. The commonest is CMV, which can produce acute encephalitis, sometimes with focal hemisphere or brain-stem signs, dementia, retinitis, optic neuritis and an ascending radiculomyeloencephalitis. Cryptococcal meningitis is the most frequent fungal disease; a high degree of clinical suspicion is required in patients with fever, malaise, headache or seizures. Only CSF cultures are always positive; both serum and CSF cryptococcal antigen tests are highly sensitive and specific. Treatment with amphotericin B and flucytosine is successful in at least 70% of first episodes but side-effects are common. Without maintenance therapy 50% of patients relapse; fluconazole is recommended. Cerebral toxoplasmosis can present with focal cerebral or spinal cord signs but also as a diffuse encephalopathy; negative T. gondii serology is exceptional but positive serum titres are usually unhelpful. Treatment with sulfadiazine, pyrimethamine and folinic acid achieves good results in 90% of the first episodes, but side-effects are common. Appearances on CT scan or MRI may take several weeks to improve. The value of an empirical approach to treatment is well-established; an initial cerebral biopsy is difficult to justify. Without maintenance therapy a relapse rate of 50% can be expected; therapy with sulfadiazine and pyrimethamine may also prevent pneumocystosis. HIV disease appears to increase the likelihood of neurosyphilis, and the risk of relapse after conventional penicillin doses, in patients with syphilis; at least 3-4 weeks of appropriate therapy are recommended. A number of other diseases caused by viruses, fungi, bacteria and parasites are less common; these include progressive multifocal leukoencephalopathy, herpes simplex and zoster infections and tuberculosis.

AIDS-Related Opportunistic Infections↗