Anterior horn cell degeneration in polymyositis associated with human T lymphotropic virus Type-1 in patients from Barbados

Anterior horn cell degeneration has only ocassionally 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, elctromyographic findings were compatible with motor unit loss and muscle biopsies showed mononuclear inflammatory cell infiltration; muscle cell 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 cerobrospinal 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. (AU)

HLA DRBI *DQB1* haplotype in HTLV-I-associated familial infective dermatitis may predict development of HTLV-I-associated myelopathy/tropical spastic paraparesis

A possible causal association between infective dematitis and HTLV-I infection was reported familial infective dematitis (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 hitocompatibility complex (MHC), class II, human leucocyte antigen (HLA) genotyping documented a shared class II haplotype, DRB*DQBI* (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 repsonse 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. (AU)

Identification of human T-cell leukemia/lymphoma virus type I antibodies, DNA, and protein in patients with polymyositis

OBJECTIVE: To investigate a possible association between human T cell leukemia/lymphoma virus type I (HTLV-I) and polymyositis (PM). METHODS: Sera and muscle biopsy samples from 9 Jamaican PM patients were compared with specimens from American HTLV-I positive PM patients and normal controls. Sera were evaluated for HTLV antibodies by enzyme-linked immunosorbent assay and Western blot. The biopsy samples were analyzed for HTLV-I/II DNA by polymerase chain reaction and were also immunohistochemically stained for HTLV gp46 envelope protein. RESULTS: Seven of the 8 Jamaican PM patients from whom sera were available were HTLV-I seropositive. The muscle biopsies of all 9 Jamaican patients demonstrated severe lymphocytic infiltration, cellular degeneration, myofiber atrophy, and fibrosis. Each muscle biopsy specimen contained HTLV-I DNA. Two of 6 samples demonstrated intense staining for HTLV-I gp46 in many of the invading mononuclear cells and weak staining for HTLV-I gp46 in many of the other specimens were weakly positive for gp46 in rare mononuclear cells. All controls specimens were negative for the presence of HTLV-I DNA and protein. CONClUSION: HTLV-I is associated with an inflammatory muscle disease characterized by direct invasion of the affected muscle by HTLV-I-infected mononuclear cells.(AU)

Anterior horn cell degeneration in HTLV-1 associated polymyositis in patients from Barbados - abstract

Anterior horn cell degeneration has only been noted occasionally in patients with tropical spastic paraparesis associated with human T-lymphotropic virus type I infection (HTLV-I). We report on three adult patients with HTLV-I associated polymyositis who had evidence of anterior horn cell degeneration. One patient had moderate proximal weakness in all 4 limbs, while 2 had mild upper limb weakness and profound proximal weakness in the lower limbs. Electromyographic findings indicated motor unit loss. Muscle biopsies in 2 patients showed features of denervation, as well as mono-nuclear inflammatory cell infiltration. HTLV-1 IgG antibodies were detected by enzyme-linked immunosorbent assay, and confirmed by Western-immunoblot, in serum and cerebrospinal fluid in all 3 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-p 19 HTLV-1 mouse monoclonal antibody. These 3 cases illustrate the variety of neuromuscular disease, other than spastic paraparesis, that may occur in HTLV-1 infection. Anterior horn cell degeneration may coexist with HTLV-1 associated polymyositis and may make a significant contribution to the muscle atrophy observed in these cases (AU)

Human spongiform encephalopathy: the National Institutes of Health series of 300 cases of experimentally transmitted disease

We present a synthesis of clinical, neuropatholgical, and biological details of the National Institutes of Health series of 300 experimentally transmitted cases of spongiform encephalopathy from among more than 1,000 cases of various neurological disorder inoculated into nonhuman primates during the past 30 years. The series comprises of 278 subjects with Creutzfeldt-Jakob disease, of whom 234 had sporadic, 36 familial, and 8 iatrogenic disease; 18 patients with kuru; and 4 patients with Gerstmann-Straussler-Scheinker syndrome. Sporadic Creutzfeldt-Jakob disease, numerically by far the most important representative, showed an average age at onset of 60 years, with the frequent early appearance of cerebellar and visual/oculomotor signs, and a broad spectrum of clinical features during the subsequent course of illness, which was usually fatal in less than 6 months. Characteristic spongiform neuropathology was present in all but 2 subjects. Microscopically visible kuru-type amyloid plaques were found in 5 percent of patients with Creutzfeldt-Jakob disease. 75 percent of those with kuru, and 100 percent of those with Gerstmann-Straussler-Scheinker syndrome; brain biopsy was diagnostic in 95 percent of cases later confirmed at autopsy, and proteinase-resistant amyloid protein was identified in Western blots of brain extracts from 88 percent of tested subjects. Experimental transmission rates were highest for iatrogenic Creutzfeldt-Jakob disease (100 percent), kuru (95 percent), and sporadic Creutzfeldt-Jakob disease (90 percent), and considerably lower for most familiar forms of disease (68 percent). Incubation periods as well as the durations and character of illness showed great variability, even in animals receiving the same inoculum, mirroring the spectrum of clinical profiles seen in human disease. Infectivity reached average levels of nearly 10(to the 5th power) median lethal doses/gm of brain tissue, but was only irregularly present (and at much lower levels) in tissues outside the brain, and, except for cerebrospinal fluid, was never detected in bodily secretions or excretions (AU)

Isolation and characterization of HTLV-I from symptomatic family members with tropical spastic paraparesis (HTLV-I encephalomyeloneuropathy)

Human T lymphotropic virus type I (HTLV-I) was isolated from peripheral blood- and cerebrospinal fluid-derived mononuclear cells of a 13-y-old boy and from the peripheral blood lymphocytes of both his parents. All three had IgG antibodies to HTLV-I and varying degrees of the clinical features of tropical spastic paraparesis (TSP). The son also had IgG antibodies specific for HTLV-I in his serum. Isolations were successfully made from peripheral blood lymphocytes and cerebrospinal fluid lymphocytes stimulated with interleukin-2 or cocultivated with umbilical cord blood mononuclear cells. Established cell lines contained HTLV-I antigen by immunfluorescence and cell-associated virus by electron microscopy; cells became transformed in vitro as determined by their continuous growth in the absence of exogenous interleukin-2. This boy is the youngest TSP patient known to be reported, and the isolation of HTLV-I from all three family members suggests the causative role of this virus in TSP. (AU)

Comparison of a human T-cell lymphotropic virus type I strain from cerebrospinal fluid of a Jamaican patient with tropical spastic paraparesis with a prototype human T-cell lymphotropic virus type I

The isolation and characterization of a human T-cell lymphotrophic 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.(AU)

HTLV-I-like viral particles in spinal cord cells in Jamaican tropical spastic paraparesis

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. (AU)

Pathological and immunological observations on tropical spastic paraparesis in patients from Jamaica

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 cerebrospnal fluid were available, antibodies to the human T-lymphotropic virus type 1 were found. (AU)

The role of HTLV-I in tropical spastic paraparesis in Jamaica

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 percent of sera and 77 percent of cerebrospinal fluids. On Westren 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 wer normal, and IgG indexes indicated intrathecal IgG synthesis. Histopathological changes showed a chronic inflammatry reaction with mononuclear cell infiltration, perivascular cuffing, and demyelination that was predominant in the lateral colmns. In 1 patient, a retrovirus morphologically similar to HTLV-I on electron microscopy was isolated from spinal fluid. Our investgations show that endemic tropical spastic paraparesis in Jamaica is a retrovirus-assiciated myelopathy and that HTLV-I or an antigenically similar retrovirus is the causal agent. (AU)