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Neuroepidemiology of human T-lymphotrophic virus type-I-associated tropical spastic paraparesis.

Tropical spastic paraparesis (TSP) is a chronic neurological syndrome of gradual onset involving the pyramidal tracts and upper motor neurons, resulting in weakness and stiffness of the lower extremities, hyperactive tendon reflexes, spasticity, low back pain, and urinary disturbances. Clusters of endemic TSP have been noted in Africa, the Seychelles Islands, Colombia, and the Caribbean. Recently, studies have linked human T-lymphotrophic virus type-I (HTLV-I) with the endemic form of the disease. In Japan a very similar clinical syndrome has been identified as HTLV-I-associated myelopathy and may be a non-tropical version of the same disease. The purpose of the present review is to examine the role HTLV-I may play in the pathogenesis of these myelopathies from a neuroepidemiological point of view.

Adult↗

Immunological studies in tropical spastic paraparesis.

Tropical spastic paraparesis (TSP) and other chronic-progressive myelopathies have been clearly associated with increased serum and cerebrospinal fluid antibody titers to human T-lymphotropic virus type I (HTLV-I). However, little is known about the cellular immune function in TSP. In the present study, activated T lymphocytes were found in the peripheral blood of patients with TSP. Specifically, there were increased numbers of large CD3+ cells that also expressed HLA-DR and interleukin-2-receptor molecules. A significantly elevated spontaneous lymphoproliferative response was demonstrated in all patients tested. Generation of measles virus-specific cytotoxic T-cell response was reduced in 4 of 4 patients. This was similar to previous findings in patients with multiple sclerosis. However, unlike multiple sclerosis, reduced generation of cytotoxic T-cell response to influenza and mumps viruses was observed in 2 of 4 patients. These observations confirm further the strong association between TSP and an HTLV-I-like virus and suggest that the observed abnormalities of the cellular immune response in TSP are related to infection of lymphocytes by the retrovirus.

Adolescent↗

Intrathecal synthesis of antibodies to human T lymphotropic virus type I and the presence of IgG oligoclonal bands in the cerebrospinal fluid of patients with endemic tropical spastic paraparesis.

Tropical spastic paraparesis (TSP), a neuromyelopathy predominantly involving the pyramidal tract and commonly observed in tropical and equatorial areas, was recently found to be associated with human T lymphotropic virus type I (HTLV-I). We investigated sera and cerebrospinal fluid (CSF) from 19 patients with TSP who were from the Caribbean area, French Guiana, and Africa. Our results showed an elevated intra-blood-brain barrier IgG synthesis rate and an elevated IgG index, with an increased HTLV-I antibody-to-albumin ratio and the presence of CSF oligoclonal bands in the majority of the patients. These data, in association with similar HTLV-I antibody patterns between patients with TSP who were from these three regions, strengthen the probable etiologic role of HTLV-I in the pathogenesis of such chronic neuromyelopathies.

Adult↗

Isolation of an HTLV-1-like retrovirus from patients with tropical spastic paraparesis.

Tropical spastic paraparesis (TSP) is a slowly progressive myelopathy associated with increased serum and cerebrospinal fluid antibodies to the human T-lymphotropic retrovirus type I (HTLV-I) (ref. 1), and has been observed in many regions of the world. A similar condition known as HTLV-I-associated myelopathy occurs in the Kagoshima prefecture of Japan. Recent but controversial reports suggest involvement of virus related to HTLV-I in multiple sclerosis. Magnetic resonance imaging and electrophysiological studies indicate that TSP lesions are like multiple sclerosis in that they are disseminated throughout the nervous system. Complete virus from patients with TSP has proved difficult to isolate using techniques successful in adult T-cell leukaemia cases associated with HTLV-I. Here we report the isolation of an HTLV-I-like virus from T-cell lines derived from the peripheral blood and cerebrospinal fluid of TSP patients. The monoclonal antibody OKT3 was used to generate non-transformed T-cell lines that express HTLV-I antigens. Infectious virus was demonstrated by co-cultivation and complete, replicating virions were visualized ultrastructurally.

Antigens, Viral↗

[Tropical spastic paraparesis in the tropics and Brazil. A historical analysis].

The tropical spastic paraparesis (TSP) is a chronic myelopathy, predominant in the tropics, recently known to be of retroviral origin (HTLV-I). This paper aims at delineating the clinico-etiological evolution of this entity. The historical analysis of it showed that the TSP has had, along decades, many different denominations and the discovery of the retroviral origin for some of them has stimulated new paths of research and epidemiological interest in the tropics and Brazil.

Brazil↗

Tropical spastic paraparesis in Kerala.

Tropical Spastic Paraparesis (TSP) is an uncommon myeloneuropathy with an insular geographic distribution. In 1985, Human T-lymphotropic virus type I (HTLV-1) was reported to be a possible etiological factor. We did an epidemiological, clinical and virological study of 25 cases of TSP. They were predominantly young adult men, whose duration of illness ranged from 6 months to 15 years. Difficulty in walking, stiffness of legs and paraesthesia of legs were the main symptoms. None had tuberculosis, syphilis, malnutrition or lathyrism. Pyramidal signs of the lower limbs, upper limbs, posterior column involvement and spinothalamic tract dysfunction were the common signs. Laboratory findings and cerebrospinal fluid analysis were normal in most. Myelograms or MRI were normal in all. Only 1 case repeatedly tested positive for HTLV-1 antibodies. None of his relatives had clinical or virological evidence of TSP or HTLV-1 infection. Based on our study, we could not link HTLV-I infection to TSP in Indian cases. Virological testing for HTLV-I infection by polymerase chain reaction may be a better tool to reveal such an association. Our cases were similar to seronegative spinal spastic paraplegia. A related new retrovirus or an altered immune response to HTLV-1 due to environmental or dietary factors are possibilities which require further exploration.

Adolescent↗

Low HTLV-1 seroprevalence in endemic tropical spastic paraparesis in Ethiopia.

Tropical spastic paraparesis (TSP), a chronic progressive myelopathy, occurs in Ethiopia in epidemic form as neurolathyrism, while the endemic form has remained obscure. We describe the clinical features of 22 patients with TSP and the results of screening for HTLV-1 in these patients, 26 patients with other neurological disorders, 14 patients with leukaemia and 66 blood donors. The major manifestations in the patients with TSP were weakness and spasticity of the lower limbs with upper motor neurone signs and minimal sensory loss and bladder dysfunction. Two patients with TSP (9%), 2 patients with other neurological disorders (7.7%) and one patient with leukaemia and deafness were seropositive for HTLV-1. All the 66 blood donors were seronegative. Our results suggest that HTLV-1 may not play a major role in the pathogenesis of TSP in Ethiopia.

Adolescent↗

Urinary dysfunction in tropical spastic paraparesis: preliminary urodynamic survey.

Tropical spastic paraparesis is an infection caused by human T lymphotropic virus type 1 (HTLV-1). We present the urodynamic findings in 4 female and 1 male patient with tropical spastic paraparesis. All patients underwent synchronous video-pressure-flow urodynamics, while 3 also underwent electromyographic examination. Of the 5 patients 4 presented with detrusor external sphincter dyssynergia and 1 had detrusor hyperreflexia with a coordinated sphincter contraction. The preliminary results of this series suggest that patients with tropical spastic paraparesis and voiding symptoms should undergo urodynamic examination so that diagnosis and appropriate therapy may be instituted.

Adult↗

Human T-lymphotropic virus type I antibodies in the serum of patients with tropical spastic paraparesis in the Seychelles.

Tropical spastic paraparesis (TSP), a chronic myelopathy of unknown etiology, was studied in the Seychelles. Human T-lymphotropic virus type I (HTLV-I) and human immunodeficiency virus antibodies were determined using an enzyme-linked immunosorbent assay and confirmed with an indirect fluorescent antibody test in serum samples of 20 patients with TSP and 16 controls. Test results indicated that 17 patients (85%) and two controls (transverse myelopathy and clinically probable multiple sclerosis) were positive for HTLV-I. Serum samples of nine healthy controls and five with other neurologic diseases were negative for HTLV-I. No serum samples were positive for human immunodeficiency virus. Estimated relative risk for TSP in those subjects whose serum is positive for HTLV-I antibodies is 40. This result is highly statistically significant. Although primarily associated with adult T-cell leukemia and non-Hodgkin's lymphoma, HTLV-I could also be an etiologic agent of TSP.

Adult↗

Brazilian studies on tropical spastic paraparesis. A meta-analysis.

Tropical spastic paraparesis (TSP) is a chronic progressive myelopathy and in most of the cases has a retroviral (HTLV-1) etiology, when it is denominated HTLV-1 associated-mielopathy (HAM/TSP). Around 433 cases of TSP have been described in Northeast and Southeast Brazil. Among these cases, 157 (36.2%) are HTLV-1 positive and 276 (63.7%) are negative. Their mean age is 43.8 years with a slight predominance of females and mulattoes, although white patients are also numerous. Clinically all patients exhibit a spastic paraparesis with variable sphincter and sensory disturbance. Pain and autonomic symptoms seem to be expressive in the HTLV-1 positive HAM/TSP Brazilian patients.

Adult↗

HTLV-I negative tropical spastic paraparesis: a scientific challenge.

We reviewed the historical, clinical and etiological aspects of the progressive chronic spastic myelopathies of unknown etiology, disserting on the clinical similarities between HTLV-I seropositive and seronegative tropical spastic paraparesis (TSP), as well as focusing on the PCR studies of the seronegative TSP.

Diagnosis, Differential↗

Tropical spastic paraparesis on the Caribbean coast of Colombia.

Tropical spastic paraparesis (TSP) is a retroviral disease characterized predominantly by a chronic myelopathy and progressive leg weakness. Four patients from the northern coast of Columbia with chronic spastic paraparesis and serum positivity for antibodies to human T cell lymphotropic virus type 1 by enzyme-linked immunosorbent assay and Western blot are reported. All patients had mixed ethnic origins (white, black, and amerindian). This is the first report of TSP on the Caribbean coast of Colombia. This study extends the geographic boundaries of TSP in the Caribbean basin.

Adult↗

The neuroepidemiology of tropical spastic paraparesis.

Recent neuroepidemiological studies of endemic tropical spastic paraparesis (TSP) have confirmed the existence of high-prevalence foci in several tropical islands, including Jamaica and Martinique in the Caribbean, Tumaco off the Pacific coast of Colombia, and the Seychelles in the Indian Ocean. There is a net preponderance of TSP in persons of Black African ancestry, although Caucasian, Hindu, Amerindian, and Orientals have been affected. The epidemiological, clinical, laboratory, and neuropathological features of TSP are reviewed here, as well as the evidence in favor of its retroviral origin.

Adolescent↗

Human T-lymphotropic virus type I (HTLV-I) and tropical spastic paraparesis or HTLV-I-associated myelopathy in Hawaii.

Tropical spastic paraparesis or human T-lymphotropic virus type I (HTLV-I)-associated myelopathy is a degenerative encephalomyelopathy with pyramidal tract dysfunction affecting the lower extremities. It is associated with HTLV-I infection and found primarily in the Caribbean region and in southwestern Japan. Five cases of tropical spastic paraparesis (or HTLV-I-associated myelopathy) in Hawaii are reported. All five patients were born in Hawaii; four are women. Each of the patients has parents who were from HTLV-I-endemic areas of Japan. Two of these patients had serum antibodies to HTLV-I. Five of six of the spouses and children of the seropositive patients were also seropositive. Viral cultures of lymphocytes from both seropositive patients and two of the three seropositive children were positive for HTLV-I. None of the five patients had a history of antecedent blood transfusion, multiple sexual partners, or intravenous drug use. There is no evidence of adult T-cell leukemia or lymphoma in any of the patients or their families. Given the increasing seroprevalence of HTLV-I in the United States, clinicians need to be alert to new cases of this disorder.

Back Pain↗

Tropical spastic paraparesis in Northeastern Brazil.

Ten possible cases of tropical spastic paraparesis (TSP) in Northeastern Brazil (Ceará) are presented. They show the typical symptoms and signs of TSP consisting of weakness of the lower limbs, spastic gait, hyperreflexia, bladder dysfunction and variable signs of posterior columns impairment. The laboratory examinations excluded other compressive, infective, degenerative or demyelinating lesions of their spinal cord. Our patients age ranged from 21 to 59 years, all were of black origin and all were of lower social class. There was a slight preponderance of females. An etiological implication of a retrovirus (HTLV-I) has been shown for TSP, but for lack of technical conditions we could not determine it in our patients, and that stands as our subsequent step in those and further cases.

Adult↗

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% 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.

Adolescent↗

Human T-cell lymphotropic virus type 1 infection and tropical spastic paraparesis in Belgian expatriates.

A case of HTLV-1 associated tropical spastic paraparesis is described in a Belgian nun who had been working as a midwife in Central Africa. Occupational exposure was the only risk factor identified. Among 2,482 Belgian expatriates in tropical countries, 92% of whom had resided in sub-Saharan Africa for an average of 15.5 years, only one Belgian-born man was found seropositive for HTLV-1. He was married to an African woman and living in Central Africa for 23 years. The risk of HTLV-1 infection is low in Belgian expatriates and on its own does not support generalised anti-HTLV screening in autochthonous Belgian blood donors.

Belgium↗

Evolution in a chronic RNA virus infection: selection on HTLV-I tax protein differs between healthy carriers and patients with tropical spastic paraparesis.

HTLV-I causes T-cell leukemia and tropical spastic paraparesis (TSP) in a minority of infected people, whereas the majority remain healthy. The virus differs little in sequence between isolates but has been shown to have a quasispecies structure. Using the Nei and Gojobori algorithm, we have shown that the proportion of nonsynonymous to synonymous changes in HTLV-I proviral tax gene sequences from healthy seropositive subjects (Dn/Ds = 0.9 to 1.3) is significantly higher than those from TSP patients (Dn/Ds = 0.3 to 0.6). Here we show that the distinction between healthy seropositives and TSP patients can only be seen with proviral tax sequences, but not with cDNA, the amino-terminal or carboxy-terminal half of tax, or the rex gene. The Dn/Ds ratio of proviral tax sequences was used to analyze two TSP patients with atypical features and to investigate the influence of cytotoxic T cells (CTL) on the viral quasispecies.

Biological Evolution↗