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)

Human T-lymphotropic virus type 1: a retrovirus causing chronic myeloneuropathies in tropical and temperate climates

Human T-cell lymphotropic virus type I (HTLV-I), the first human retrovirus to be isolated, is the cause of endemic tropical spastic paraparesis (TSP). Originally, this chronic neurological disorder was described as a disease seen among blacks of low socioeconomic status living in tropical countries, and thus for many decades TSP remained a little known curiousty outside the endemic regions. The link between HTLV-I infection and TSP was made fortuitously, when antibodies to HTLV-I were found in serum and cerebrospinal fluid of TSP patients in Jamaica, Colombia, and Martinique. Soon thereafter a similar disorder, designated HTLV-I associated myelopathy (HAM), was reported from southern Japan. This broadened the geographic and ethnic boundaries of this chronic myelopathy and the disease has now been reported in multiple ethnic groups from more than 40 countries, in both tropical and temperate regions. The name TSP/HAM is now used to include all patients (regardless of race or country of origin) who have HTLV-I-positive endemic TSP or HAM. (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)

Tropical myeloneuropathies: a new aetiology

Tropical myeloneuropathies are a group of neurological disorders known to occur in subtropical and tropical regions. Many aetiologies have been postulated and investigated over the past 100 years, but no single cause has been found. Recent studies suggest that human T-cell lymphotropic virus HTLV-I is the causative agent of one of these tropical myeloneuropathies, endemic tropical spastic paraparesis, and of a related disorder in southern Japan called HTLV-I-associated myelopathy. Endemic tropical spastic paraparesis is now being reported from geographical and climatic regions that were previously thought to be free of these disorders. (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)