Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Magnetic resonance imaging (MRI) of the brain was studied in 35 patients with HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP), 19 HTLV-I seropositive carriers without HAM/TSP (non-HAM/TSP carriers), 18 patients with HTLV-I seronegative spastic spinal paraparesis (SSP), and 82 HTLV-I seronegative controls with other neurological disorders. The incidence of white matter lesions was significantly higher in HAM/TSP (66%) than in the controls (23%) and SSP (11%). HAM/TSP exceeded non-HAM/TSP carriers significantly in the incidence of multiple white matter lesions (37% vs 10%). HAM/TSP affected the deep and subcortical cerebral white matter multifocally, sparing the periventricular regions. None of the lesions were enhanced by gadolinium-DTPA. HAM/TSP patients with the white matter lesions had both a longer duration of disease and a greater disability than did those without lesions. The white matter lesions gradually increased in number, as the disability status became worse, in spite of the high dose corticosteroid treatment. All these observations suggest that the MRI abnormalities of the HAM/TSP brain may reflect the chronic perivascular inflammation with progressive gliosis (chronic disseminated encephalomyelitis). We propose that brain MRI can be successfully utilized as a reliable and non-invasive measure for following the disease progression in HAM/TSP.
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PMID:Leukoencephalopathy in HTLV-I-associated myelopathy/tropical spastic paraparesis: MRI analysis and a two year follow-up study after corticosteroid therapy. 177 38

Human T-lymphotropic virus type I (HTLV-I), the etiological agent of adult T-cell leukemia/lymphoma, also appears to be the cause of tropical spastic paraparesis, a chronic myelopathy reported in several different regions of the world. The prevalence of antibodies to HTLV-I in patients with chronic neurodegenerative disorders other than tropical spastic paraparesis and in patients with some muscle inflammatory disorders has been investigated. IgG antibodies to HTLV-I were measured in the sera and/or cerebrospinal fluid from 82 Guamanian patients with amyotrophic lateral sclerosis and parkinsonism-dementia, 164 Guamanian normal controls, 10 patients with kuru from the Eastern Highlands of Papua New Guinea, 4 patients with Viliuisk encephalomyelitis from the Iakut region of eastern Siberia, 45 Italian patients with multiple sclerosis, and 56 patients with polymyositis (49 from the United States and 7 from Jamaica). As determined by enzyme-linked immunosorbent assay, Western immunoblot, and gelatin particle agglutination techniques, serological evidence of HTLV-I infection was found in 1 patient with amyotrophic lateral sclerosis and 1 control subject from Guam, and in 1 patient from the United States and all 7 Jamaican patients with polymyositis. Except for the high seropositivity rate among the group of Jamaican patients with polymyositis, our data indicate that HTLV-I is an unlikely causative agent in the spectrum of the neurological diseases examined. The seropositivity of the 7 Jamaican patients with polymyositis requires further study.
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PMID:Seroprevalence of antibodies to HTLV-I in patients with chronic neurological disorders other than tropical spastic paraparesis. 289 13

The consequences of human retroviral infections have had an unprecedented impact on the medical, scientific, and social institutions of the last two decades of this century. The nervous system as an end target organ figures prominently in the constellation of diseases associated with HTLV and HIV infection and numerous syndrome complexes have been recognized that reflect dysfunction of the brain, spinal cord, nerve roots, peripheral nerves, or muscle. HAM/TSP, associated with HTLV-I and rarely with HTLV-II infections, and encephalomyelitis, associated with HIV infection, may present with clinical, laboratory, neuroelectrophysiologic, and neuroimaging features closely resembling MS. A careful systematic search for associated disease processes and review of the medical history, however should raise the suspicion of possible retroviral infection. In the appropriate setting, because of the pleiotropy in disease expression and the high prevalence of retroviral infection in many areas of the United States, clinicians should have a low threshold for ordering diagnostic testing for HIV and HTLV when considering a retroviral cause for a neurologic disorder. The retroviruses are pervasive throughout the vertebrate subphylum and share common elements within their genome that encode for promoters and structural proteins and are distinguished from each other by sets of transactivating and regulating genes. The latter group of genes serve to regulate viral replication by the induction and post-transcriptional and post-translational modification of retrovirally encoded gene products. In addition, the transactivating gene products can activate and upregulate the expression of a variety of host cellular genes, many of which possess immune-related functions. The viral particle or specific components of certain viral structural proteins may be directly toxic to neural tissues. Also, during the replicative phase, retroviruses are recognized by host defense mechanisms, which mount considerable cellular and humoral immune responses. The spectrum of retroviral-associated neurologic diseases therefore may represent a complex interaction among viral antigen-induced immunity, the production of neurotoxic viral peptides, and the abnormal induction and expression of cellular genes with potent bioactivity.
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PMID:Human retroviruses and demyelinating diseases. 773 6

Identification of the localization of human T lymphotrophic virus type I (HTLV-I) proviral DNA in the central nervous system (CNS) is crucial to the understanding of the pathogenesis of HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP) pathogenesis. We have developed a sensitive detection method, called two-step polymerase chain reaction (PCR) in situ hybridization, which enabled us to detect the HTLV-I proviral DNA in paraffin-embedded spinal cord tissue sections from HAM/TSP patients. HTLV-I proviral DNA was detected only in the nucleus of lymphocytes that had infiltrated into the spinal cord. However, no proviral DNA was amplified in any neuronal cells, including neurons and glial cells. This indicates that the demyelination of the spinal cord by HTLV-I as a result of viral infection of oligodendrocytes or neuronal cells is unlikely. The T cell receptor V beta gene sequence from lymphocytes in the spinal cord lesions taken from the same HAM/TSP autopsy cases revealed unique and restricted CDR3 motifs, CASSLXG(G) (one-letter amino acid. X is any amino acid), CASSPT(G), and CASSGRL which are similar to those described in T cells from brain lesions of multiple sclerosis (MS) and in a rat T cell clone derived from experimental allergic encephalomyelitis (EAE) lesions. The present results suggest that T cells containing restricted V beta CDR3 motifs, which are also found in MS and EAE, become activated upon HTLV-I infection and infiltrate into the spinal cord lesions of HAM/TSP patients.
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PMID:Detection of human T lymphotrophic virus type I (HTLV-I) proviral DNA and analysis of T cell receptor V beta CDR3 sequences in spinal cord lesions of HTLV-I-associated myelopathy/tropical spastic paraparesis. 806 35

Human T-cell lymphotropic virus type I (HTLV-I) induces a chronic demyelinating disease known as HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). While only 0.25% of HTLV-I-infected individuals develop HAM/TSP, the mechanisms responsible for the progression of an HTLV-I carrier state to clinical disease are not clear. In particular, no specific sequence differences have been found between HTLV-I recovered from HAM patients and HTLV-I-infected carriers. Since CD4 T cells are the major reservoir of the virus, at least three hypotheses implicating CD4 T cells directly or indirectly have been proposed: 1) The cytotoxic hypothesis predicts that activated and HTLV-I-infected CD4 T cells migrate to the CNS and infect resident cells. Cytotoxic CD8 T cells may then recognize viral antigens on HTLV-I-infected CNS cells causing a cellularly mediated cytotoxic demyelination. 2) The autoimmune hypothesis predicts that either (a) virally reactive T cells crossreact with a CNS antigen, or (b) random infection of CD4 T cells eventually results in the infection of CNS-autoreactive CD4 T cells that, by virtue of the productive HTLV-I infection, become activated, expand and migrate to the CNS, where they encounter their antigen. This results in a specific immune response and demyelination, as is known to occur in experimental autoimmune encephalomyelitis. 3) The bystander damage hypothesis does not implicate a specific response against CNS cells. Instead this hypothesis suggests that the presence of IFN-gamma-secreting HTLV-I-infected CD4 T cells and their recognition by virally specific CD8 T cells in the CNS induce microglia to secrete cytokines, such as TNF-alpha, which may be toxic for the myelin.
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PMID:Pathogenesis of chronic progressive myelopathy associated with human T-cell lymphotropic virus type I. 917 44

South Africa has one of the fastest growing HIV epidemics in the world and KwaZulu-Natal, one of its nine provinces, is the epicentre of the epidemic. Of the estimated 5.3 million people infected with HIV in South Africa, 1.2 million reside in KwaZulu-Natal. Transmission of HIV is almost exclusively heterosexual, intravenous drug misuse does not occur and the patients attending state hospitals are antiretroviral drug naive. The neurological complications of HIV infection include bacterial and fungal meningitis, intracranial mass lesions, acute disseminated encephalomyelitis, a variety of spinal cord disorders, and peripheral nerve dysfunction. Tuberculous meningitis, especially that due to multidrug resistant organisms has a high mortality rate. Toxoplasmosis is the most frequent cause of intracranial mass lesions. These cases are successfully treated with cotrimoxazole alone. Multiple bacterial abscesses and tuberculomata are other important causes whilst primary central nervous system lymphoma is rare. The spinal cord disorders include co-infection with HTLV-I, tuberculosis and syphilis. Intramedullary tuberculomata, often multiple, and spinal epidural tuberculous abscess without bony disease are seen more commonly than in the pre HIV era. Peripheral nerve dysfunction include Gillian Barre Syndrome, chronic inflammatory demyelinating polyneuropathy and mononeuritis multiplex. Until the antiretroviral therapy roll out programme is well established the above HIV related neurological complications will continue to be seen for several years.
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PMID:Neurological manifestations of HIV infection in Kwazulu-Natal South Africa. 1596 Feb 36