RESUMEN
Human T-cell lymphotropic virus type I (HTLV-I), is the cause of endemic tropical spastic paraparesis (TSP) or HTLV-I-associated myelopathy (HAM). Because TSP/HAM is not a fatal disease, the neuropathology of this disease, albeit relatively well understood, is based on the examination of just a few incidental cases. Previously, we demonstrated peculiar lamellated structures, called "multilamellar bodies" (MLB). In this report, we present the ultrastructural neuropathology of a TSP/HAM case from Chile, with further detailed descriptions of MLB. It is tempting to suggest that MLB may represent specific ultrastructural markers of TSP/HAM. The pathology of the anterior and posterior horns was similar and was comprised of axonal degeneration, accompanied by extensive astrocytic gliosis. Lymphocytic infiltration, particularly observed as "cuffs" around blood vessels, was scattered among other cellular elements. Ultrastructurally, myelin sheaths were relatively well preserved, and some demyelinated but not remyelinated fibers were observed. Moreover, axons with abnormal accumulations of neurofilaments, suggestive of axonal degeneration, were detected. Several axons contained Hirano bodies. In many samples, glial processes replaced most of the remaining neuropil. In a few specimens of the anterior and posterior horns of the spinal cord, MLB were observed. These structures consisted of stacks of 30 to 40 electron-dense lamellae, which were interrupted by narrow electron-lucent spaces. All of the lamellae were immersed within an amorphous substance of intermediate density. Neurons of the dorsal root ganglia were basically normal except for increased lipofuscin accumulation. As in the spinal cord, myelinated axons were well preserved, but a few were demyelinated and surrounded by concentric arrays of Schwann cell membranes. Also, axons of the dorsal roots accumulated increased number of neurofilaments. Mast cells and Schwann cells were increased in number, the latter containing abundant pi granules and myelin fragments.
Asunto(s)
Lóbulo Frontal/ultraestructura , Ganglios Espinales/ultraestructura , Músculo Esquelético/ultraestructura , Paraparesia Espástica Tropical/patología , Médula Espinal/ultraestructura , Astrocitos/ultraestructura , Axones/ultraestructura , Chile , Glucógeno/metabolismo , Humanos , Lipofuscina/metabolismo , Linfocitos/patología , Vaina de Mielina/ultraestructura , Miofibrillas/ultraestructura , Neurofibrillas/ultraestructura , Vacuolas/ultraestructuraRESUMEN
OBJECTIVE: To determine whether subjects coinfected with HTLV-I and HIV have a higher frequency of myelopathy than subjects singly infected with HIV. DESIGN: A prospective, nested case-control study of HTLV-I and HIV coinfected (cases) and HIV singly infected adults (controls) participating in a prospective HIV cohort study at a university hospital outpatient HIV clinic in Rio de Janeiro, Brazil. MEASUREMENTS: Subjects were evaluated for evidence of myelopathy by a neurologist unaware of their HTLV serologic status. Patients with at least two pyramidal signs, such as paresis, hypertonicity or spasticity, hyperreflexia, clonus, diminished or absent superficial reflexes, or the presence of pathologic reflexes (e.g., Babinski or Hoffmann), were defined as having myelopathy. Myelopathy severity was quantified using the Kurtzke Functional Disability Scale (FDS); patients with FDS scores > or = 4 were considered to have significant myelopathy. Selected patients with myelopathy underwent lumbar puncture for the evaluation of intrathecal synthesis of HTLV-I antibodies. RESULTS: Of 15 coinfected subjects, 11 (73%) had evidence of myelopathy versus 10 of 62 subjects (16%) with HIV single infection (adjusted odds ratio [OR] = 13.0, p = 0.00002). When only myelopathy patients with FDS scores of > or = 2 or > or = 4 were included, the association between coinfection and the presence of myelopathy remained (OR = 7.3, p = 0.0003 for scores > or = 2; and OR = 8.9 for scores > or = 4, p = 0.04). In addition, a higher proportion of coinfected subjects had peripheral neuropathy (40%) than controls (16%) (OR = 3.5, p = 0.07). CONCLUSION: Coinfection with HTLV-I was strongly associated with myelopathy among subjects infected with HIV. The relative contribution of HTLV-I versus HIV in the pathogenesis of coinfection-associated myelopathy is not known. Coinfection may also be associated with peripheral neuropathy. Further studies are needed to elucidate the mechanisms of coinfection-associated neurologic conditions.
Asunto(s)
Infecciones por VIH/complicaciones , Infecciones por HTLV-I/complicaciones , Paraparesia Espástica Tropical/complicaciones , Paraparesia Espástica Tropical/epidemiología , Adulto , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Estudios ProspectivosRESUMEN
Anterior horn cell degeneration has only occasionally been noted in patients with tropical spastic paraparesis associated with human T lymphotropic virus type-1 (HTLV-1) infection. We report on three adult patients with HTLV-1-associated polymyositis who had clinical evidence of anterior horn cell degeneration. One patient had moderate proximal weakness and muscle wasting in all four limbs, while two had mild upper limb weakness with more profound proximal weakness and wasting in the lower limbs. In all three patients, electromyographic findings were compatible with motor unit loss and muscle biopsies showed mononuclear inflammatory cell infiltration; muscle biopsies in two patients showed features of denervation. Immunoglobulin G (IgG) antibodies to HTLV-1 were detected by enzyme-linked immunosorbent assay (ELISA) and confirmed by Western immunoblot in serum and cerebrospinal fluid in all three patients. In two, cell cultures were established from peripheral blood lymphocytes and HTLV-1 antigen was identified by immunofluorescence and the ELISA antigen-capture technique using an anti-p19 HTLV-1 mouse monoclonal antibody. The three cases illustrate the variety of neuromuscular disease, other than spastic paraparesis, that may occur in HTLV-1 infection. In some cases of HTLV-1-associated polymyositis, anterior horn cell degeneration may make a significant contribution to the muscle atrophy observed.
Asunto(s)
Células del Asta Anterior/patología , Infecciones por HTLV-I/patología , Polimiositis/patología , Adulto , Barbados , Femenino , Estudios de Seguimiento , Anticuerpos Anti-HTLV-I/sangre , Anticuerpos Anti-HTLV-I/líquido cefalorraquídeo , Infecciones por HTLV-I/complicaciones , Infecciones por HTLV-I/inmunología , Infecciones por HTLV-I/virología , Virus Linfotrópico T Tipo 1 Humano/aislamiento & purificación , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/líquido cefalorraquídeo , Persona de Mediana Edad , Polimiositis/complicaciones , Polimiositis/inmunología , Polimiositis/virologíaRESUMEN
Reports of an 18-fold higher incidence of schizophrenia among second-generation Afro-Caribbeans, and especially Jamaican migrants in the United Kingdom were soon called "an epidemic of schizophrenia," with the inference that a novel virus, likely to be perinatally transmitted, was a possible etiological agent. This intriguing observation led us to explore a possible link with human T-cell lymphotropic virus type one (HTLV-I), because it is a virus that is endemic in the Caribbean Island, is perinatally transmitted, known to be neuropathogenic, and the cause of a chronic myelopathy (tropical spastic paraparesis/HTLV-I associated myelopathy. We therefore examined inpatients as the Bellevue Mental Hospital, Kingston, Jamaica and did standard serological tests for retroviruses HTLV-I and HTLV-II and HIV-I and HIV-II on 201 inpatients who fulfilled ICD-9 and DSM III-R criteria for schizophrenia. Our results produced important negative data, since the seropositivity rates for HTLV-I, the most likely pathogen, were no greater than the seropositivity range for HTLV-I carriers in this island population, indicating the HTLV-1 and the other retroviruses tested do not play a primary etiological role in Jamaican schizophrenics.
Asunto(s)
Retroviridae/aislamiento & purificación , Esquizofrenia/virología , Adulto , Anticuerpos Antivirales/sangre , Femenino , VIH-1/aislamiento & purificación , VIH-2/aislamiento & purificación , Virus Linfotrópico T Tipo 1 Humano/aislamiento & purificación , Virus Linfotrópico T Tipo 2 Humano/aislamiento & purificación , Humanos , Inmunoglobulina G/sangre , Incidencia , Jamaica/epidemiología , Jamaica/etnología , Masculino , Persona de Mediana Edad , Esquizofrenia/epidemiología , Clase Social , Reino Unido/epidemiologíaRESUMEN
A possible causal association between infective dermatitis and HTLV-I infection was reported in 1990 and confirmed in 1992. We now report familial infective dermatitis (ID) occurring in a 26-year-old mother and her 9-year-old son. The mother was first diagnosed with ID in 1969 at the age of 2 years in the Dermatology Unit at the University Hospital of the West Indies (U.H.W.I.) in Jamaica. The elder of her 2 sons was diagnosed with ID at the age of 3 years, also at U.H.W.I. Both mother and son are HTLV-I-seropositive. A second, younger son, currently age 2 years, is also HTLV-I-seropositive, but without clinical evidence of ID. Major histocompatibility complex (MHC), class II, human leucocyte antigen (HLA) genotyping documented a shared class II haplotype, DRB1*DQB1* (1101-0301), in the mother and her 2 sons. This same haplotype has been described among Japanese patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and has been associated with a possible pathologically heightened immune response to HTLV-I infection. The presence of this haplotype in these familial ID cases with clinical signs of HAM/TSP may have contributed to their risk for development of HAM/TSP. The unaffected, HTLV-I-seropositive younger son requires close clinical follow-up.
Asunto(s)
Dermatitis/etiología , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Infecciones por HTLV-I/inmunología , Paraparesia Espástica Tropical/inmunología , Enfermedades Cutáneas Infecciosas/etiología , Adulto , Niño , Preescolar , Dermatitis/genética , Dermatitis/inmunología , Femenino , Genotipo , Cadenas beta de HLA-DQ , Cadenas HLA-DRB1 , Infecciones por HTLV-I/complicaciones , Infecciones por HTLV-I/genética , Haplotipos , Prueba de Histocompatibilidad , Humanos , Jamaica , Masculino , Paraparesia Espástica Tropical/epidemiología , Linaje , Valor Predictivo de las Pruebas , Enfermedades Cutáneas Infecciosas/genética , Enfermedades Cutáneas Infecciosas/inmunologíaRESUMEN
We have found the codon 200Lys mutation in 6 Chilean CJD families, including a family in the rural case cluster in Chillán. Thus, all 3 of the known clusters of CJD, in Slovakia, Libyan-born Israeli Jews, and Chile, are linked to the presence of the same mutation. The phenotypic features of the disease in these families are similar to those reported for other clustered or individual families elsewhere in the world. The heterogeneous genetic composition of the Chilean population interpreted in light of historical migration patterns suggests that the mutation may have entered Chile by Jewish emigration from Spain.
Asunto(s)
Precursor de Proteína beta-Amiloide/genética , Cromosomas Humanos Par 20 , Síndrome de Creutzfeldt-Jakob/genética , Adulto , Anciano , Precursor de Proteína beta-Amiloide/biosíntesis , Encéfalo/patología , Química Encefálica , Codón , Síndrome de Creutzfeldt-Jakob/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , Linaje , Fenotipo , Bazo/patologíaRESUMEN
This study presents an analysis of the factors associated with HTLV-I seroprevalence in the endemic area of Tumaco, Colombia. During June to August 1988, 1,077 individuals were selected at random from a population of 45,594. The overall prevalence rate of HTLV-I antibodies was 2.8%. Among females prevalence was significantly higher (p less than 0.02) than among males. Rates increased substantially with age. HTLV-I prevalence among individuals with history of use of intravenous medications was significantly higher (p less than 0.001) than in those without such history. Logistic regression analysis included age in years, indicators for male gender, and for i.v. injections, and their interactions. Age was very strongly associated to HTLV-I infection among females. At early ages prevalence was not different between sexes, but females presented a significantly higher rate than males after age 42. History of i.v. administered medications was very strongly associated in the univariate analysis and, although significance was borderline in the multivariate analysis, it had the effect of doubling the odds of HTLV-I infection.
Asunto(s)
Anticuerpos Antivirales/sangre , Infecciones por HTLV-I/epidemiología , Adolescente , Adulto , Niño , Preescolar , Colombia/epidemiología , Femenino , Infecciones por HTLV-I/inmunología , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Prevalencia , Distribución Aleatoria , Análisis de Regresión , Factores de Riesgo , Estudios SeroepidemiológicosRESUMEN
We screened 140 patients with different neurological diseases for the presence of anti HTLV-1 virus antibodies. ELISA test confirmed with Western Blot analysis was performed in CSF and blood. Positive findings were obtained in 23 out of 52 patients with progressive spastic paraparesis (44%). All patients with multiple sclerosis, polymyositis, amyotrophic lateral sclerosis or chronic polyneuropathy were negative. Patients with progressive spastic paraparesis and positive HTLV-1 antibodies were most commonly women (78%) and middle aged (mean 46 years old), with a history of surgical interventions (70%) or blood transfusion (35%). A slowly progressive spastic paraparesis with asymmetric onset and minimal sensory complaints was observed in some cases. Mononuclear pleocytosis in the CSF was observed in 35% with an increased IgG index in 88%. A delayed latency and low amplitude of somatosensory evoked potentials was observed in 89% of patients.
Asunto(s)
Anticuerpos Anti-HTLV-I/análisis , Enfermedades del Sistema Nervioso/microbiología , Paraparesia Espástica Tropical/microbiología , Adolescente , Adulto , Anciano , Western Blotting , Chile , Ensayo de Inmunoadsorción Enzimática , Potenciales Evocados , Femenino , Virus Linfotrópico T Tipo 1 Humano/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/inmunología , Enfermedades del Sistema Nervioso/fisiopatología , Paraparesia Espástica Tropical/inmunología , Paraparesia Espástica Tropical/fisiopatologíaRESUMEN
The isolation and characterization of a human T-cell lymphotropic retrovirus related to human T-cell lymphotropic virus type I (HTLV-I) from cerebrospinal fluid of a Jamaican patient with tropical spastic paraparesis is described. The virus isolate is a typical type C retrovirus as seen by electron microscopy and is related to prototype HTLV-I isolated from patients with adult T-cell leukemia but is not identical to this prototype HTLV-I as seen by restriction enzyme mapping.
Asunto(s)
Líquido Cefalorraquídeo/microbiología , Virus Linfotrópico T Tipo 1 Humano/aislamiento & purificación , Paraparesia Espástica Tropical/microbiología , Anciano , Células Cultivadas , Enzimas de Restricción del ADN , ADN Viral/análisis , Anticuerpos Antideltaretrovirus/análisis , Femenino , Técnica del Anticuerpo Fluorescente , Virus Linfotrópico T Tipo 1 Humano/enzimología , Virus Linfotrópico T Tipo 1 Humano/genética , Humanos , Jamaica , Leucemia de Células T/microbiología , Leucocitos Mononucleares/microbiología , Microscopía Electrónica , Paraparesia Espástica Tropical/inmunología , ADN Polimerasa Dirigida por ARN/análisisRESUMEN
Viral-like particles morphologically identical to human T-lymphotropic virus type I or II, but distinct from human T-lymphotropic virus type III, have been seen by electron microscopy in spinal cord tissue from a Jamaican tropical spastic paraparesis patient who was known to be positive for human T-lymphotropic virus I antibody before death. This is the first electron microscopy report on a patient from an endemic tropical spastic paraparesis region.
Asunto(s)
Deltaretrovirus/aislamiento & purificación , Paraplejía/microbiología , Médula Espinal/microbiología , Adulto , Femenino , Humanos , Jamaica , Microscopía Electrónica , Espasticidad Muscular/microbiología , Espasticidad Muscular/patología , Paraplejía/patología , Médula Espinal/patología , Clima TropicalRESUMEN
We report clinical and laboratory investigations of 47 native-born Jamaican patients with endemic tropical spastic paraparesis and of 1 patient with tropical ataxic neuropathy. Mean age at onset was 40 years, with a female-male preponderance (2.7:1). Neurological features of endemic tropical spastic paraparesis are predominantly those of a spastic paraparesis with variable degrees of proprioceptive and/or superficial sensory impairment. Using enzyme-linked immunoabsorbent assay (ELISA), IgG antibodies to human T-lymphotropic virus type I (HTLV-I) were present in 82% of sera and 77% of cerebrospinal fluids. On Western blot analysis, IgG antibodies detected the p19 and p24 gag-encoded core proteins in both serum and cerebrospinal fluid. Titers were tenfold higher by ELISA in serum than in cerebrospinal fluid, and some oligoclonal bands present in fluid were not seen in serum. Serum-cerebrospinal fluid albumin ratios were normal, and IgG indexes indicated intrathecal IgG synthesis. Histopathological changes showed a chronic inflammatory reaction with mononuclear cell infiltration, perivascular cuffing, and demyelination that was predominant in the lateral columns. In 1 patient, a retrovirus morphologically similar to HTLV-I on electron microscopy was isolated from spinal fluid. Our investigations show that endemic tropical spastic paraparesis in Jamaica is a retrovirus-associated myelopathy and that HTLV-I or an antigenically similar retrovirus is the causal agent.
Asunto(s)
Infecciones por Deltaretrovirus/complicaciones , Paraplejía/etiología , Medicina Tropical , Adolescente , Adulto , Anciano , Anticuerpos Antiidiotipos/análisis , Anticuerpos Antivirales/análisis , Deltaretrovirus/aislamiento & purificación , Anticuerpos Antideltaretrovirus , Femenino , Humanos , Inmunoglobulina G/inmunología , Jamaica , Masculino , Persona de Mediana Edad , Espasticidad Muscular/líquido cefalorraquídeo , Espasticidad Muscular/etiología , Espasticidad Muscular/inmunología , Paraplejía/líquido cefalorraquídeo , Paraplejía/inmunologíaRESUMEN
Three of 6 patients with spastic paraparesis in Lima, Peru, were found to have antibodies to human T-lymphotropic virus type I (HTLV-I). Blood and cerebrospinal fluid antibodies were confirmed by Western blot analysis. Multilobulated lymphocytes in blood and cerebrospinal fluid of the index case stained with monoclonal antibodies for T-helper cells and for T10, an activation marker. Blood mononuclear cells from patients with HTLV-I-associated myelopathy showed spontaneous proliferation in culture, evidence of interleukin-2 receptors, and decreased natural killer cell activity.
Asunto(s)
Infecciones por Deltaretrovirus , Paraplejía/etiología , Adulto , Anciano , Anticuerpos Antivirales/análisis , Anticuerpos Antivirales/líquido cefalorraquídeo , Células Sanguíneas/patología , División Celular , Anticuerpos Antideltaretrovirus , Infecciones por Deltaretrovirus/líquido cefalorraquídeo , Infecciones por Deltaretrovirus/inmunología , Infecciones por Deltaretrovirus/patología , Femenino , Humanos , Leucocitos Mononucleares/patología , Masculino , Persona de Mediana Edad , Espasticidad Muscular/líquido cefalorraquídeo , Espasticidad Muscular/etiología , Espasticidad Muscular/inmunología , Espasticidad Muscular/patología , Mielitis/etiología , Paraplejía/líquido cefalorraquídeo , Paraplejía/inmunología , Paraplejía/patología , Perú , Linfocitos T/clasificaciónRESUMEN
The neuropathological examination of the spinal cord of 2 Jamaican patients with classical tropical spastic paraparesis disclosed an intense chronic meningomyelitis with demyelination. In the 1 case in which serum and cerebrospinal fluid were available, antibodies to the human T-lymphotropic virus type 1 were found.
Asunto(s)
Paraplejía/patología , Medicina Tropical , Adulto , Anticuerpos Antiidiotipos/análisis , Anticuerpos Antiidiotipos/líquido cefalorraquídeo , Anticuerpos Antivirales/análisis , Anticuerpos Antivirales/líquido cefalorraquídeo , Encéfalo/patología , Anticuerpos Antideltaretrovirus , Femenino , Humanos , Inmunoglobulina G/inmunología , Jamaica , Espasticidad Muscular/inmunología , Espasticidad Muscular/patología , Paraplejía/inmunología , Médula Espinal/patologíaRESUMEN
The clinical syndrome earlier designated as paraparesia espástica del Pacífico is an isolated form of tropical spastic paraparesis (TSP) that was reported in 1981 in the southern Pacific lowlands of Columbia in and near Tumaco. The clinical features are similar to those of TSP reported in Jamaica, Martinique, the Seychelles, and the Ivory Coast of Africa and resemble also those clinical features of the human T-lymphotropic virus type I (HTLV-I)-associated myelopathy described in southern Japan. Since HTLV-I infection is closely associated with TSP, we conducted a case-control study to evaluate the role of HTLV-I-associated risk factors among patients from the endemic focus in Tumaco, Colombia, and the seroprevalence rates of this virus in other geographical areas of the Pacific Colombian lowlands with and without TSP. From our seroprevalence study of antibodies to HTLV-I among TSP index patients, matched controls, household contacts (first- and second-degree relatives), and healthy controls from these areas, we found a strong association between HTLV-I and TSP. Also, there is a high seroprevalence of HTLV-I among sexual partners of patients and to a lesser extent among their offspring and other relatives some of whom had an early mean acquisition of antibodies to HTLV-I. Heterosexual promiscuity and other close interpersonal contact may play an important role in the transmission of TSP in the Pacific lowlands of Colombia.