SEARCH · PubMed Health

Results for “Paraparesis, Spastic”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources

PubMedDate not supplied

The presence of HTLV-I proviral DNA in the central nervous system of patients with HTLV-I-associated myelopathy/tropical spastic paraparesis.

Human T-lymphotropic virus type 1 (HTLV-I) is a pathogenic retrovirus associated with a chronic progressive myelopathy, termed HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP), as well as adult T-cell leukemia (ATL). A chronic inflammatory process has been implicated in HAM/TSP by a pathological study, but the exact mechanism still remains unknown. To understand better the complex mechanism of disease induction by HTLV-I, I studied the spreading pattern of HTLV-I in both peripheral blood mononuclear cells (PBMNCs) and central nervous system (CNS) tissues in patients with HAM/TSP using a quantitative polymerase chain reaction (PCR) method. My results indicated the primary event to be the efficient replication of HTLV-I in vivo, whereas HTLV-I is likely to be present in the constituent cells of the CNS in addition to the infiltrating mononuclear cells.

Central Nervous System↗

PubMed1995

Risk factors and cofactors for human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Jamaica.

Human T-cell lymphotropic virus type I (HTLV-I) has been etiologically associated with a neurologic syndrome called HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) as well as with adult T-cell leukemia/lymphoma. The authors sought to quantify the risk in Jamaica of HAM/TSP associated with HTLV-I infection and cofactors associated with this disease among infected individuals. Between 1988 and 1989, prevalent and incident HAM/TSP patients and controls with other neurologic diseases were enrolled in a retrospective study. A second control group was composed of HTLV-I-seropositive, asymptomatic carriers in Jamaica, ascertained in a separate study conducted in 1988. Although HTLV-I seropositivity was not a component of the case definition for HAM/TSP, all 43 HAM/TSP patients were HTLV-I seropositive compared with two (4.0%) of the controls with other neurologic diseases. Given HTLV-I seropositivity, one cofactor associated with the risk of HAM/TSP was young age at initial heterosexual confidence interval 1.29-12.46 for individuals aged < or = 15; odds ratio = 4.26, 95% confidence interval 1.41-12.90 for individuals aged 16-17 years at initial intercourse). Among individuals who reported this early age at initial sexual intercourse, an increased risk of HAM/TSP was associated with having reported more than five lifetime sexual partners (odds ratio = 2.88, 95% confidence interval 0.90-8.70). Neither an early age at initial sexual intercourse or the number of lifetime sexual partners was a risk factor for adult T-cell leukemia/lymphoma. These data support the hypothesis that HAM/TSP is associated with sexually acquired HTLV-I infection, whereas adult T-cell leukemia/lymphoma is not.

Adolescent↗

PubMed1988

Spastic paraparesis and HTLV-I infection in Peru.

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.

Adult↗

PubMed1999

Genetic localization of a new locus for recessive familial spastic paraparesis to 15q13-15.

OBJECTIVE: To characterize a new gene locus for familial spastic paraparesis (FSP). BACKGROUND: FSP is a genetically heterogeneous group of upper motor neuron syndromes. It can be inherited as an autosomal dominant, autosomal recessive, or X-linked disorder. Four loci for autosomal dominant FSP have been genetically mapped, and two genes have been shown responsible for the X-linked type. In addition, two loci for autosomal recessive type have been reported and mapped to chromosomes 8q and 16q. The gene for the 16q locus has been characterized as a mitochondrial protein. METHODS: Eight recessive FSP families from America and Europe were used for genetic linkage analysis. The known recessive loci (8q and 16q) and the X-linked loci (PLP and L1CAM genes) were screened through PCR amplification, followed by linkage analysis, single-strand conformational polymorphism, or both. RESULTS: All the families except one revealed lack of linkage to the known loci for recessive and X-linked types of FSP. One of the eight families showed data consistent with linkage to the previously characterized 8q locus. Analysis of all the families for possible linkage to other candidate loci revealed significant positive lod scores for markers in chromosome 15q. The maximum multipoint combined lod score for the non-8q families was Z = 3.14 for markers D15S1007, D15S971, D15S118, and D15S1012, at a distance of 6.41 cM from the marker D15S1007, in between D15S971 and D15S118. CONCLUSIONS: Our data suggest a new locus for recessive FSP linked to chromosome 15q, and that this may be the most common one.

Adolescent↗

PubMed2004

Longer dinucleotide repeat polymorphism in matrix metalloproteinase-9 (MMP-9) gene promoter which correlates with higher HTLV-I Tax mediated transcriptional activity influences the risk of HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP).

Matrix metalloproteinase-9 (MMP-9) has been reported to be expressed in various inflammatory disorders including human T cell lymphotropic virus type I (HTLV-I) associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-I-infected T-cells expressed high levels of MMP-9 via viral transactivator Tax mediated activation of the MMP-9 promoter. To investigate whether the d(CA) repeat polymorphism in MMP-9 promoter affects the risk of developing HAM/TSP, we compared the allele frequencies between 200 HAM/TSP patients and 200 HTLV-I seropositive asymptomatic carriers (HCs). The longer d(CA) repeat alleles of MMP-9 promoter, which was associated with higher Tax-mediated transcriptional activity, was more frequently observed in HAM/TSP patients than HCs (p<0.01 by Mann-Whitney U-test). The length alteration of this d(CA) repeat in the MMP-9 promoter may cause phenotypic differences among HTLV-I infected infiltrating cells and may thereby be in part responsible for the development of HAM/TSP.

Adult↗

PubMed1993

Neuroaxonal dystrophy in HTLV-1-associated myelopathy/tropical spastic paraparesis: neuropathologic and neuroimmunologic correlations.

Detailed neuropathologic and immunohistologic analysis of a case of serologically and polymerase chain reaction-confirmed human immunodeficiency virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is reported in a 73-year-old North American black woman. In addition to the usual neuropathologic features of HAM/TSP, including tractal degeneration of the spinal cord, leptomeningeal and perivascular fibrosis, perivascular demyelination and chronic inflammation, neuroaxonal spheroids were prominent in the spinal cord. Neuroaxonal dystrophy was characterized by neurofilamentous masses that were immunoreactive for phosphorylated neurofilament epitopes, but not ubiquitin. Neuroimmunologic analysis of the inflammatory reaction revealed a prevalence of CD8+ T cells and class I major histocompatibility molecules (MHC) (HLA-ABC and beta 2-microglobulin), but very few CD4+ T cells. Microglia were highly reactive for class II MHC (HLA-DR alpha) and this was attributed to activation, rather than CD4 interaction, since CD4 presence was minimal. Inflammatory cytokine immunoreactivity was also detected in glia. It is concluded that the cumulative effects of cytotoxic T cell (CD8) infiltration and the possible involvement of cytokines were responsible for the unusual degree of neuroaxonal dystrophy and vascular fibrosis, as well as the observed demyelination in this case.

Aged↗

PubMed1995

Characterization of cerebral white matter lesions of HTLV-I-associated myelopathy/tropical spastic paraparesis in comparison with multiple sclerosis and collagen-vasculitis: a semiquantitative MRI study.

The brain lesions were studied by magnetic resonance imaging (MRI) in 29 HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), 43 multiple sclerosis (MS) (11 with a primary progressive course: PPMS and 32 with a relapsing-remitting course: RRMS), 23 collagen-vasculitis and 54 HTLV-I-seronegative patients with other non-inflammatory neurological disorders (OND), according to the size of the lesions and their location in the brain (deep and subcortical white matter, periventricular white matter, infratentorial region and gray matter). Semiquantitative MRI analyses revealed the followings. (1) The frequency of either small or large lesions located in the periventricular as well as deep and subcortical white matter was significantly higher in HAM/TSP than in OND patients (p < 0.006, chi 2 test). In addition, the number of small lesions in the deep and subcortical, and periventricular white matter was significantly greater in HAM/TSP than in OND patients (p < 0.0003, Mann-Whitney U-test). (2) The HAM/TSP patients significantly exceeded the collagen-vasculitis patients in the frequency and the number of small lesions located in the periventricular region (p < 0.0001, chi 2 test, and p < 0.05, Mann-Whitney U-test, respectively), although no difference was found in case of those in the deep and subcortical white matter. (3) The HAM/TSP group had a lower frequency of small deep and subcortical white matter, small infratentorial and large periventricular lesions than the entire MS group (p < 0.05, chi 2 test). The PPMS group greatly exceeded the HAM/TSP group in the number of MRI lesions in all brain regions (p < 0.05, Mann-Whitney U-test), whereas RRMS and HAM/TSP patients showed a similar number of lesions (p > 0.1, Mann-Whitney U-test). Both the difference between HAM/TSP and collagen-vasculitis and the similarities between HAM/TSP and RRMS in the MRI features suggest that although all commonly have a vasculitic process as a necessary component, some other factor, probably with demyelinating effects, is operative HAM/TSP.

Adult↗

PubMedDate not supplied

Sicca syndrome and HTLV-I-associated myelopathy/tropical spastic paraparesis.

PURPOSE: The objective of this study is to describe the clinical and immunological aspects observed in patients with both human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis and ocular dryness. METHODS: In 15 such patients, clinical and biological examinations completed with a biopsy of secondary salivary glands were performed to assess the etiology of the ocular dryness. RESULTS: Histological study of the biopsy specimens indicated that 80% of the patients had grade 3 or grade 4 lesions, according to the Chisholm scale. Polyclonal hypergammaglobulinemia was found in 60% of patients and lymphocytic alveolitis in 80%. Three patients had past medical history of chronic uveitis. CONCLUSIONS: All findings in these patients were compatible with Sjögren's syndrome; however, no immunological disorders characteristic of the syndrome were found. Tests for antinuclear antibodies and rheumatoid factor proved negative in all cases.

Adult↗

PubMed2003

Usefulness of proviral load measurement for monitoring of disease activity in individual patients with human T-lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis.

High human T-lymphotropic virus type I (HTLV-I) proviral load in peripheral blood mononuclear cells (PBMCs) has been reported in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and the proviral load has been reported to fluctuate in individual patients during the course of the disease. Clinical symptoms usually became stable after a prolonged period of symptom progression. However, the authors have experienced having some patients whose clinical manifestations suddenly became worse during the course of the disease. To clarify the role of high proviral load and its fluctuation in the pathogenesis of HAM/TSP, the authors measured the proviral load of serially taken PBMCs as well as of cerebrospinal fluid (CSF) cells from patients with HAM/TSP on long-term follow-up and compared these with their clinical manifestations. There was a wide distribution of proviral load, from 0.3 to 37.8 copies/100 PBMCs; however, the proviral load in individual patients was relatively stable during the course of the disease. Eighty-three percent of the patients with clinical worsening showed an increase in proviral load at the time point when clinical worsening was recorded, or at the preceding time point. The proviral loads in CSF cells were higher than those in PBMCs in individual patients. The ratio of proviral loads in CSF cells/in PBMCs, but not the absolute load, in either compartment, was significantly associated with clinically progressive disease and with recent onset of HAM/TSP. These findings indicate that clinical progression of HAM/TSP is associated with increased proliferation or immigration of HTLV-I-infected lymphocytes in the central nervous system.

Aged↗

PubMed1994

[Hepatitis B virus antibody positive spastic paraparesis].

We present here thirteen patients (5 men and 8 women, aged 31 to 73, mean 55 years) with spastic paraparesis who showed clinical features similar to those of HTLV-1 associated myelopathy without HTLV-1 antibody, but with positive antibody to hepatitis B virus (HBV). All of these patients showed slowly progressive difficulty in walking. Five patients had previous histories of blood transfusion, of these one with history of B hepatitis. Neurologically, muscle weakness, spasticity and exaggerated deep tendon reflexes in the lower extremities were common to all the patients. Seven patients showed Babinski's reflex. Disturbance of micturition was noted in 3 patients. None showed organic changes of the spine on magnetic resonance image (MRI). None was serologically positive for syphilis and had cryoglobulin and hypergammaglobulinemia. Elevated levels of the liver enzymes were noted in two patients. All patients were positive for hepatitis B surface antibody (HBs-Ab) (EIA) but negative for hepatitis B surface antigen (HBs-Ag) (EIA). Five patients were seropositive for hepatitis C virus (HCV) (PHA). In 3 of them, reverse transcriptase polymerase chain reaction was performed but failed to detect HCV-RNA. All patients underwent spinal tap, and showed normal cell count and protein concentration in their cerebrospinal fluid (CSF). Atypical cells were not observed in all the patients. The CSFs from three patients were tested for HBs-Ag and HBs-Ab. HBs-Ag was negative in all three patients, but HBs-Ab was positive in two patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

Cell surface phenotype and human T lymphotropic virus type 1 antigen expression in 12 T cell lines derived from peripheral blood and cerebrospinal fluid of West Indian, Guyanese and African patients with tropical spastic paraparesis.

Twelve long-term cell lines were established from peripheral blood mononuclear cells (PBMC) or cerebrospinal fluid cells of patients with human T lymphotropic virus type I (HTLV-1) seropositive tropical spastic paraparesis (TSP) originating from the French West Indies, French Guyana or the Central African Republic. Most of these long-term interleukin-2-dependent cell lines exhibited a pattern characteristic of CD4(+)-activated T cells with high expression of CD2, CD3 and CD4 antigens, associated with a strong density of TAC and DR molecules. Nevertheless, in five cases CD8 expression was present at a significant level. HTLV-I antigens were never detected in uncultured PBMC, but they were expressed in a few cells after short-term culture and after 4 months the majority of the cells were HTLV-I positive, as demonstrated by indirect immunofluorescence (IF) using polyclonal or monoclonal anti-p19 and anti-p24 antibodies. Low and variable levels of reverse transcriptase activity were detected in supernatant fluids of these cell lines only after 4 months of culture, when at least 50% of the cells exhibited HTLV-I antigens by IF. However, numerous type C HTLV-I-like viral particles were detected, mostly in the extracellular spaces, with rare budding particles. Similar findings were found in three T cell lines derived from West Indian and African patients with adult T-cell leukaemia/lymphoma (ATLL). Differences in high Mr polypeptides were detected by Western blot in cell lysates when comparing TSP- or ATLL-derived T cell lines. Thus a signal of 62K was easily detectable in all the TSP lines, but not in the ATLL lines. In all cell lines bands corresponding to p53, p24 and p19 viral core polypeptides were present, as was the env gene-coded protein p46.

Adult↗

PubMed1990

A cluster of HTLV-1 associated tropical spastic paraparesis in Equateur (Zaire): ethnic and familial distribution.

In Lisala, Equateur province, Zaire, 25 patients from 21 pedigrees were identified with human T-lymphotropic virus type 1 (HTLV-1) associated tropical spastic paraparesis (TSP). In the 10 (48%) pedigrees with additional genuine TSP cases established mainly by history, seven of 10 patients' mothers, no fathers or spouses, one of 59 surviving offspring, five of 105 siblings, and six other close blood relatives had TSP. A child may develop TSP before its mother. Three familial cases were in paternal relatives only. In total, 39 cases (11 men, 28 women) were identified in this population of about 50,000. Half were in the Mundunga minority of less than or equal to 10% (p less than 0.001). The data suggest maternal transmission of HTLV-1 and enhanced TSP susceptibility in those infected due to familial, probably genetic factors.

Adolescent↗

PubMed1995

HTLV-I associated tropical spastic paraparesis. Cerebral spinal fluid evolutive aspects in 128 cases.

In order to evaluate if there is variation on the intensity of cerebral spinal fluid (CSF) response during HTLV-I associated tropical spastic paraparesis (TSP) evolution we retrospectively reviewed 128 cases. The results indicate that although CSF inflammatory alterations can persist over a 10-year period, they tend to become slight or even absent after the second year of TSP evolution.

Adult↗

PubMedDate not supplied

HTLV-I, infective dermatitis, and tropical spastic paraparesis.

Since human T-cell lymphotropic virus (HTLV-I) was identified in 1980 as causing human disease, it has been etiologically associated with adult T-cell lymphoma/leukemia (ATL) and tropical spastic paraparesis (TSP). More recently, several new diseases have been reported in association with this virus, including infective dermatitis of Jamaican children, which we reported in 1990. Studies on infective dermatitis have shown that these children have abnormalities of immune function, and some develop other HTLV-I associated disorders, including TSP. This paper reviews the work done on infective dermatitis to date, and explores the association with TSP.

Adult↗

PubMed1996

Antibody-dependent cell-mediated cytotoxicity (ADCC) in HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP)

Defects in immune surveillance mechanisms may allow increased replication of human T-lymphotropic virus type I (HTLV-I) in peripheral blood mononuclear cells in HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). To explore this possibility, antibody-dependent cell-mediated cytotoxicity (ADCC) against HTLV-I infected cells in HAM/TSP and in asymptomatic HTLV-I-seropositive carriers (SPC), was studied. ADCC activity was significantly depressed in HAM/TSP compared to SPC subjects (p < 0.025) and was due to specific reduction in ADCC effector activity. On the other hand, there was no difference in antibody component of anti-HTLV-I ADCC (ADCC-Ab) activities between HAM/TSP and SPC, although patients with more severe forms of disease tended to have higher anti-HTLV-I ADCC-Ab activity. In HAM/TSP, depressed ADCC activity against HTLV-I due to reduced ADCC-effector activity may allow increased replication of HTLV-I which may implicate the development of inflammatory neuropathologic lesions of HAM/TSP.

Adult↗

PubMed1990

Nucleotide sequence analysis of a provirus derived from an individual with tropical spastic paraparesis.

Human T-cell lymphotropic virus type 1 (HTLV-1), the cause of inapparent infections and T-cell leukemias and lymphomas, has also been implicated in two chronic neurological diseases, tropical spastic paraparesis (TSP) and HTLV-1 associated myelopathy (HAM). We initiated a search for a neurotropic variant of HTLV-1 that might be responsible for these chronic progressive myelopathies by cloning and sequencing a provirus from a T-cell line from an individual with TSP. The LTRs and genes of the TSP provirus differ from HTLV-1 by 20-30 nucleotides in each region, but none of the substitutions ostensibly affect functional sites with the exception of the env gene. We document one substitution in the region encoding gp46 common to TSP and HAM proviruses and a mutation that introduces two stop codons in the region encoding gp21. The latter should delete about 100 amino acids from the transmembrane anchor, and, for this reason, the progeny of the sequenced provirus are likely to be defective viruses, maintained in the culture through coinfection of cells with wild-type non-defective HTLV-1. While defective viruses could be responsible for persistent infection of the nervous system in TSP, this cannot be generally the case as we show that HTLV-1 DNA amplified from cell lines from two other individuals with TSP lacked the stop codons. Similarly, comparisons of DNA amplified from HTLV-1 DNA in cases of ATL, HAM, and TSP did not establish a correlation between the mutation in gp46 and neurological disease. The issue of neurotropic variants in HTLV-1 associated neurological disease thus remains an open one which may be resolved in the future by examining proviruses in cells in the lesions in the nervous system; or proviruses in ATL and HAM/TSP which differ in their ability to replicate in glial or neuronal cells.

Amino Acid Sequence↗

PubMed2005

Disability profile of patients with HTLV-I-associated myelopathy/tropical spastic paraparesis using the Functional Independence Measure (FIM).

STUDY DESIGN: Survey. OBJECTIVE: To determine the disability profile of a group of patients with human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), using the Functional Independence Measure (FIM) to identify the most affected functional areas. SETTING: Reference center for HTLV Rio de Janeiro, Brazil. METHODS: A total of 72 patients (49 female and 23 male), consecutively referred by tertiary care centers, were assessed using the FIM. RESULTS: The average FIM score was 108 (+/-12 SD) ranging from 58 to 122. The lowest items scores were obtained in locomotion and bladder management. When divided into two groups (above, and below or equal to the average score), there were significant differences (P<0.05) in age at time of assessment, in the degree of muscular power and in low back pain. There were no significant differences in terms of age of onset and duration of the disease. CONCLUSIONS: The most affected areas in FIM motor items were locomotion (walk and stairs) and bladder management. Age, strength in lower limbs and low back pain interfere with functional activities in patients with HAM/TSP. The duration of the disease is not a significant factor for patient disabilities. The goals of rehabilitation in HAM/TSP patients should target the modifiable factors, such as pain, strength and the neurogenic bladder.

Activities of Daily Living↗

PubMed2000

Phylogenetic subgroups of human T cell lymphotropic virus (HTLV) type I in the tax gene and their association with different risks for HTLV-I-associated myelopathy/tropical spastic paraparesis.

The association between human T cell lymphotropic virus (HTLV) type I tax variation and disease outcome was studied. The tax gene was sequenced in 61 patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), 55 patients with adult T cell leukemia, and 62 healthy carriers (HCs). Phylogenetic analysis revealed 2 tax gene subgroups that are related on the basis of the long terminal repeat sequence. Further analysis using restriction fragment length polymorphism in 192 patients with HAM/TSP and 200 HCs revealed a higher incidence of 1 tax subgroup (taxA) in HAM/TSP. taxA was present in 30 (15.5%) of 192 patients with HAM/TSP and in 14 (7%) of 200 HCs. The difference was significant (chi2=6.47; P=.014; odds ratio, 2.46; 95% confidence interval, 1.26-4.80). This effect was independent of HLA-A*02, which has been reported to prevent HAM/TSP development. These findings suggest that both host genetic factors and HTLV-I subgroup are associated with different risks for development of HAM/TSP.

Genes, pX↗