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Background: HTLV-1-associated myelopathy is associated with constant stress, so it is very important to cope with this disease. To improve the coping of patients with this disease, it is necessary to deeply identify its barriers.Aim: The present study was conducted with aim to explain the barriers to cope with HTLV-1-associated myelopathy/tropical spastic paraparesis.Method: This qualitative content analysis approach was performed on 17 patients with HTLV-1-associated myelopathy/tropical spastic paraparesis, who referred to Ghaem hospital clinic. Data were collected by conducting semi-structured in-depth interviews in a private room of the clinic. The Graneheim and Lundman's qualitative content analysis method was used for analyzing.Results: In this study, 5 subcategories and 2 main categories (internal barriers to coping with the disease, challenges with socioeconomic barriers) were developed. The main theme abstracted was also "chains of stagnation and regression of passing the disease".Implications for Practice: Considering that health care professionals' knowledge about HTLV-1-associated myelopathy/tropical spastic paraparesis and patients' experiences is very little, the results of this study can be a basis to design a suitable and context-based care framework to improve the coping responses of patients.

Background and Objectives: HTLV-1 is responsible for two important diseases, HAM/TSP and ATLL. Approximately 10 to 20 million people are infected with HTLV-1 worldwide. Identifying altered genes in different cancers is crucial for finding potential treatment strategies. One of the proteins of the RAS/MAPK signaling pathway is MEK1, which is made from the MAP2K1 gene. The effects of the MAP2K1 gene on the MAPK signaling pathway are not yet fully elucidated. The current study aims to determine the MAP2K1 gene mutations and the level of MAP2K1 gene expression in ATLL patients compared to healthy individuals. Materials and Methods: Ten ATLL and 10 healthy control individuals were investigated in this study. We used ELISA test to screen anti-HTLV-I antibodies and PCR for confirmation of infection. Then, we extracted total RNA from fresh whole blood, and cDNA was synthesized. The expression levels of the MAP2K1 gene were examined by qRT-PCR, and to check possible mutations in the MAP2K1 gene; all samples were sequenced and analyzed by BioEdite Software. Results: MAP2K1 gene expression in the ATLL group was significantly higher than in the healthy control (P=0.001). The mutational sequencing analysis showed nucleotide 212 (SR) change and identification mutations at different nucleotides that were entirely different from the nucleotide mutations defined in the UniProt database. Conclusion: These results could be a perspective in the prevention, prognosis, and targeted treatment of diseases in which the MAP2K1 gene plays a vital role. [ABSTRACT FROM AUTHOR]

Background and Objectives: HTLV-1 is responsible for two important diseases, HAM/TSP and ATLL. Approximately 10 to 20 million people are infected with HTLV-1 worldwide. Identifying altered genes in different cancers is crucial for finding potential treatment strategies. One of the proteins of the RAS/MAPK signaling pathway is MEK1, which is made from the MAP2K1 gene. The effects of the MAP2K1 gene on the MAPK signaling pathway are not yet fully elucidated. The current study aims to determine the MAP2K1 gene mutations and the level of MAP2K1 gene expression in ATLL patients compared to healthy individuals. Materials and Methods: Ten ATLL and 10 healthy control individuals were investigated in this study. We used ELISA test to screen anti-HTLV-I antibodies and PCR for confirmation of infection. Then, we extracted total RNA from fresh whole blood, and cDNA was synthesized. The expression levels of the MAP2K1 gene were examined by qRT-PCR, and to check possible mutations in the MAP2K1 gene; all samples were sequenced and analyzed by BioEdite Software. Results: MAP2K1 gene expression in the ATLL group was significantly higher than in the healthy control (P=0.001). The mutational sequencing analysis showed nucleotide 212 (S→R) change and identification mutations at different nucleotides that were entirely different from the nucleotide mutations defined in the UniProt database. Conclusion: These results could be a perspective in the prevention, prognosis, and targeted treatment of diseases in which the MAP2K1 gene plays a vital role.

In individuals with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), spasticity is one of the main symptoms. The neurological signs of the disease are well defined, but details of how spasticity appears in these individuals have not been well explored. To describe spasticity location and severity of HAM/TSP individuals. Cross-sectional study with individuals older than 18 years, diagnosed with HAM/TSP and with lower limb spasticity. Pregnant women, individuals with other associated neurological diseases, and those using antispastic drugs were not included. Spasticity was assessed by the Modified Ashworth Scale (MAS), applied to the abductor, adductor, flexor, and extensor muscles of the hips, flexors, and extensors of the knees, dorsiflexors, plantiflexors, evertors, and inverters of the foot. Thirty participants were included. The plantiflexor muscles (90%), knee extensors (80%), knee flexors (63,3%), and adductors (50%) were most frequently affected by spasticity. Twenty-three (76.7%) individuals had mixed spasticity, 5 (16.7%) with distal spasticity and 2 (6.7%) with proximal spasticity. MAS was similar between the lower limbs in at least 6 of the 10 muscle groups of each individual. Spasticity was mostly mixed in the lower limbs, with more frequently mild severity. The individuals were partially symmetrical between the lower limbs. The most affected muscle groups were the plantiflexors, knee extensors and flexors and the hip adductors, consecutively, being predominantly symmetrical. [ABSTRACT FROM AUTHOR]

This was a cross-sectional prospective study. We performed a multivariate statistical analysis of the neurological signs and symptoms of patients infected with human T cell lymphotropic virus type 1 (HTLV-1) in an attempt to separate them into distinct groups and identify clinical-neurological manifestations that could differentiate the various profiles. The study was performed in the city of Belém (state of Pará), located in the Amazon region of Brazil, from 2014 to 2016. We determined muscle strength and tone, reflexes, sensations, sphincter function, gait, and the Expanded Disability Status Scale score among individuals with HTLV-I. We then used exploratory statistical methods in an attempt to find different profiles and establish distinct groups. We analyzed 60 patients with HTLV-1. The filtering of the data, performed with mixed PCA, gave rise to a streamlined database with the most informative data and suggested the formation of three statistically distinct groups: asymptomatic carriers (AC), mono/oligosymptomatic (MOS), and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSPd), AC and MOS (p = 0.002), AC and HAM/TSPd (p < 0.001), and HAM/TSPd and MOS (p = 0.001). The subsequent cluster analysis confirmed the formation of three clusters. The classification and regression tree demonstrated that altered gait was the most important variable for the classification of an individual with HAM/TSPd and that, in the absence of this impairment, hyperreflexia characterized MOS. The present study was able to separate patients infected by HTLV-1 into three clinical groups (AC, HAM/TSPd, and MOS) and identify clinical manifestations that could differentiate the various patient groups. [ABSTRACT FROM AUTHOR]

To evaluate the human T-cell lymphotropic virus type I (HTLV-I) proviral DNA load among asymptomatic HTLV-I-infected carriers and patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), real time PCR using TaqMan probes for the pol gene was performed in two million peripheral blood mononuclear cells (PBMC). The albumin gene was the internal genomic control and MT2 cells were used as positive control. The results are reported as copies/10,000 PBMC, and the detection limit was 10 copies. A total of 89 subjects (44 HAM/TSP and 45 healthy HTLV-I-infected carriers) followed up at the Institute of Infectious Diseases "Emilio Ribas" and in the Neurology Division of Hospital of Clínicas were studied. The asymptomatic HTLV-I-infected carriers had a median number of 271 copies (ranging from 5 to 4756 copies), whereas the HAM/TSP cases presented a median of 679 copies (5-5360 copies) in 10,000 PBMC. Thus, HAM/TSP patients presented a significantly higher HTLV-I proviral DNA load than healthy HTLV-I carriers (P = 0.005, one-way Mann-Whitney test). As observed in other persistent infections, proviral DNA load quantification may be an important tool for monotoring HTLV-I-infected subjects. However, long-term follow-up is necessary to validate this assay in the clinical setting.

[Purpose] We performed outpatient rehabilitation for a patient with HTLV-I-associated myelopathy (HAM). Because HAM easily leads to disuse-induced muscle atrophy, we needed a home exercise that would be willingly continued. Accordingly, we divided home exercise into traditional muscle training and horse-riding machine exercise periods and compared the results. [Method] In an ABAB-type single case study, home exercise was performed on a horse-riding machine utilizing trunk in the operating period and lower limb muscle training in the base level measurement period. [Results] The assessment items of sitting lateral reach, functional reach and centre of gravity sway all showed improvement during the operating period. [Conclusion] An improvement in postural balance due to home exercise on the horse-riding machine was found, and improvements in the main objectives of exercise training, housework and supported walking, were also seen. In the case of rehabilitation for HAM patients, the establishment of home exercises compatible with the domestic environment surrounding the patient is very important. The results suggest that such exercises for patients with gradually progressive and intractable diseases of the nervous system, like HAM patients, can be expected to improve functionality. [ABSTRACT FROM AUTHOR]

Human T-lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a slowly progressive, inflammatory disease of the central nervous system (CNS). We report a patient with transverse myelitis, who exhibited acute onset and rapid progression of the disease and whose symptoms resembled those observed in multiple sclerosis with spinal cord presentation. During neurological exacerbation of the condition, the HTLV-I proviral load in the cerebrospinal fluid (CSF) increased to 10 times that in the peripheral blood. This suggests that the accumulation of HTLV-I-infected cells in the CNS contributes to neurological exacerbation. Based on the increased proviral load in the CSF, we diagnosed the disease as acute progressive HAM/TSP. The measurement of the HTLV-I proviral load in the CSF is useful for the diagnosis of HAM/TSP and for monitoring its progression. [ABSTRACT FROM AUTHOR]

An autopsy case of human T-lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM) of 29 years' duration is reported. The patient had no history of surgery or blood transfusion and likely contracted HTLV-I sexually while traveling in an endemic area. At age 45, the patient began to experience gait disturbance; he later developed spastic tetraparesis. Autopsy revealed marked gross spinal cord atrophy, particularly in the middle to lower thoracic levels. Myelin and axonal degeneration were identified predominantly in the middle to lower thoracic spinal cord, extending into the medulla oblongata and lumbar cord. Inflammatory infiltrates of mononuclear cells were diffuse in the white and gray matter of the spinal cord and medulla oblongata, particularly in perivascular areas. These infiltrates were also observed in perivascular areas of the pons, midbrain, cerebellum, and cerebrum. More than half of the infiltrating cells were positive for the pan-T cell marker UCH LI, but some were positive for the B cell marker SL-26. There were far more CD8-positive cells than CD4-positive cells in the spinal parenchyma and perivascular areas. Neurons in the anterior horn, Clarke's column, and intermediolateral column were relatively well preserved. Active chronic inflammation was indicated. Despite the 29-year history of HAM, the presence of an active inflammatory reaction is surprising. We discuss possible modulation of the histopathological manifestations of HAM by corticosteroid therapy. [ABSTRACT FROM AUTHOR]

Human T lymphotropic virus I (HTLV-I)-specific cytotoxic T lymphocytes (CTL) recognize the products of the HTLV-I Tax, in the context of HLA-A2 and kill their target through a perforin-dependent mechanism. The efficiency of the CTL response may lead HTLV-I-infected individuals to remain carriers or to the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Perforin is a cytolytic molecule that contributes to CTL-mediated killing of virus-infected cells. Thus polymorphism in the perforin gene may determine the efficiency of the CTL response in HTLV-I-infected individuals. In this study, we performed single-stranded conformational polymorphism (SSCP) and DNA sequencing to analyze the promoter, 5′ UTR and first intron of the perforin gene to identify novel polymorphisms. We detected a novel polymorphism in the first intron at position +418*C/T, relative to the transcription start site. Genotyping of patients with HAM/TSP, HTLV-I carriers, and healthy controls revealed that the frequency of the C allele was statistically significantly increased in HAM/TSP patients compared with healthy controls group (p = 0.005). The frequency of the C allele was higher, but not significantly so, in the HAM/TSP group compared with HTLV-I carriers (p = 0.09), whereas there was no difference between HTLV-I carriers and healthy controls. Our results suggest that the perforin +418*C/T polymorphism is associated with the outcome of HTLV-I infection. [Copyright &y& Elsevier]

The human T-cell lymphotropic virus type 1 (HTLV-I) causes a neurological disease known as HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in a minority of infected individuals. Although other neurological outcomes have been described their prevalence is presently unknown. To evaluate the frequency and characteristics of neurological involvement in a population of HTLV-I-infected blood donors we investigated 196 HTLV-I positive and 196 negative blood donors from a blood center of Rio de Janeiro, Brazil. Individuals with abnormalities at the neurological examination were examined by three neurologists, and when pertinent, additional neurological investigations were performed. Descriptive analysis, Student''s t-test and χ2 test were employed for statistical analysis. Neurological abnormalities were found in 71 (36.2%) of the HTLV-I positive blood donors and in only 29 (14.8%) of the HTLV-I negative donors (OR=2.54, 95% CI=1.67–3.59, p=0.000002). Cases of myelopathy, motor neuron disease and myopathy were only found in the HTLV-I positive group. In addition, peripheral neuropathy (PN) was significantly more frequent in the positive group (p=0.015). In summary, our data suggest that HTLV-I-infected individuals exhibit a wide variety of neurological manifestations apart from the classical picture of HAM/TSP. [Copyright &y& Elsevier]

Human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) has been associated with changes in extracellular matrix of neural tissue. HTLV-I infection has multiple other systemic effects. Extracellular matrix is important for bone mineral deposition. We examined bone mineral density (BMD) in patients with HAM/TSP. BMD was assessed by ultrasonographic calcaneous densitometry in 24 patients (7 males, 17 females) with HAM/TPS, and 23 healthy HTLV-I-seronegative controls matched by age and sex. Patients with HAM/TPS had a mean BMD T-score of −3.07 ± 0.64 in males and −2.93 ± 0.69 in females. Control patients revealed a T-score of −0.77 ± 1.31 in males and −1.17 ± 1.08 females. The difference in T-score between HAM/TSP patients and control groups is significant (P < 0.001). Of HAM/TPS patients, 7 of 24 (29.2%) had osteopenia (T-score between −1 and −2.5) and 17 of 24 (70.8%) were diagnosed with osteoporosis (T < −2.5). Respective figures for control patients were 10 of 23 (43.5%) with a normal T-score, 11 of 23 (47.8%) with osteopenia, and 2 of 23 (8.7%) with osteoporosis. After adjustment for age and sex, odds ratio of osteoporosis for HAM/TSP patients was 31.52 (95% confidence interval, 5.07 to 195.88). No correlation was found in HAM/TSP patients between T-score and age, menstrual status, gait functionality, or years of evolution of HAM/TSP. HAM/TSP patients have a significantly diminished BMD of the calcaneous that appears not to be explained by paresis, age, years of disease, menstrual status; may be the result of systemic alterations due to HTLV-1 infection. [Copyright &y& Elsevier]

Matrix metalloproteinases (MMPs) have been reported to be involved in various inflammatory disorders. Previous studies revealed that MMP-2 and MMP-9 might play important roles in the breakdown of the blood–brain barrier (BBB) in the central nervous system (CNS) of patients with HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP). N-Biphenyl sulfonyl-phenylalanine hydroxamic acid (BPHA) selectively inhibits MMP-2, -9 and -14, but not MMP-1, -3 and -7. In the present study, we examined whether or not the selective MMP inhibitor BPHA could inhibit the heightened migrating activity of CD4+ T cells in HAM/TSP patients. The migration assay using an invasion chamber showed that migration of CD4+ T cells in HAM/TSP patients was inhibited by 25 μM BPHA. In addition, the inhibitory ratio of migrating CD4+ lymphocytes was higher in HAM patients compared to normal controls. These results suggest that the selective MMP inhibitor BPHA has therapeutic potential for HAM/TSP. [Copyright &y& Elsevier]

To investigate whether the Fas/Fas ligand (FasL) system is involved in the pathogenesis of HTLV-I associated myelopathy (HAM), expression of Fas/FasL in the spinal cord lesions of HAM patients was examined by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). Fas was preferentially expressed on infiltrating T cells in active-chronic lesions of HAM. FasL expression was up-regulated on various cells, mainly microglia/macrophages in active-chronic lesions. In contrast, Fas expression was markedly down-regulated in inactive-chronic lesions of HAM patients who had a long duration of illness. The expressions of Fas/FasL in inactive-chronic lesions were comparable to those of normal controls. In normal controls, vascular endothelial cells constitutively displayed both Fas and FasL immunoreactivity, while microglia expressed FasL. RT-PCR confirmed constitutive expression of both Fas mRNA and FasL mRNA in the spinal cords of HAM patients, and in controls. Our results indicate that Fas/FasL system is involved in the inflammatory process in the central nervous system of HAM patients. [ABSTRACT FROM AUTHOR]

Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic inflammatory disease of the spinal cord in which HTLV-I Tax-specific cytotoxic T lymphocytes (CTL) have been suggested to be immunopathogenic. However, it is unknown whether the HTLV-I-specific CTL in the central nervous system differ from those in the periphery. We investigated functional T-cell receptor diversity in HTLV-I Tax11-19-specific CTL clones derived from peripheral blood and cerebrospinal fluid (CSF) of a HAM/TSP patient using analogue peptides of the viral antigen. CTL responses to the analogue peptides varied between T-cell clones, however, CTL clones from CSF showed limited recognition of the peptides when compared to those from peripheral blood. This suggests that CTL with highly focused specificity for HTLV-I Tax accumulate in the CSF and may contribute to the pathogenesis of HAM/TSP.Furthermore, this study provides a rationale for analogue peptide-based immunotherapeutic strategies focusing on the immunopathogenic T-cells in HTLV-I-associated neurologic disease. [ABSTRACT FROM AUTHOR]

In 1985 we had the first indication that human T-cell lymphotropic virus (HTLV-I) was the possible etiological agent of a chronic myelopathy that seemed to be peculiar to the tropics and that is now known as endemic tropical spastic paraparesis (TSP). IgG antibodies to HTLV-I were found in serum and cerebrospinal fluid of patients from Jamaica, Colombia, Martinique, and shortly after in southern Japan, where the disease is called HTLV-I-associated myelopathy (HAM). The HTLV-I seropositivity was first determined by enzyme-linked immunoassay and confirmed by western immunoblot and in the cerebrospinal fluid specific IgG oligoclonal bands to HTLV-I were found in cerebrospinal fluid and not in serum. These laboratory findings indicated that HTLV-I could be neuropathogenic and for the first time a single etiological agent was identified in patients from different countries. Thus, in less than a decade a century of research and speculation was seemingly resolved when this disease, which was thought to occur only in blacks of poor socieconomic status in tropical countries, was shown to occur in all ethnic groups of varying socioeconomic status in temperate, subtropical, and tropical climates. [ABSTRACT FROM AUTHOR]

This article summarizes the present state of knowledge of TSP/HAM as it is seen in Jamaica. It reviews the historical and clinical aspects of the disease, and shows how the discovery of HTLV-I has generated research in several countries and contributed to a better understanding of the disease. It highlights the need for continued collaboration between basic scientists and clinical neurologists in order that the dilemmas relating to therapy and pathogenicity may be successfully addressed. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Paired samples of cerebrospinal fluid (CSF) and serum from 17 patients with human T-cell lymphotrophic virus I (HTLVI)-associated myelopathy, 5 patients with multiple sclerosis and 11 controls with non-inflammatory disorders (migraine, idiopathic epilepsy and myelopathy of unknown aetiology) were examined by enzyme-linked immunosorbent assay for the presence of the 60-kDa soluble form of tumour necrosis factor receptor (sTNF-R). The results were compared with blood-CSF barrier function, cell count and the intrathecal synthesis of HTLVI antibodies. No correlation could be demonstrated. High levels of sTNF-R were found in CSF of patients with HTLV-I-associated myelopathy and multiple sclerosis. In addition, intrathecal sTNF-R was also detected in the patients with non-inflammatory diseases, indicating that sTNF- R is definitively a normal constituent of CSF. [ABSTRACT FROM AUTHOR]

Fourteen patients with HTLV-1-associated myelopathy were treated with high-dose intravenous gammaglobulin (IVGG). Ten received 10 g/day of IVGG and 4 received 400 mg/kg of body-weight/day of IVGG for 5 consecutive days. Improvement of spastic paraparesis was observed in 10 within 7 days of the commencement of IVGG. The therapeutic effects were sustained for more than 3 weeks in some patients. There were no side effects. Analysis of factors of relevance to the clinical improvement with IVGG showed that the beneficial response was preferentially found in patients having a high CSF titre of anti-HTLV-I antibodies, a high CSF IgG level and a marked brain MRI abnormality. [ABSTRACT FROM AUTHOR]

We established long-term cell lines of cytotoxic T lymphocytes (CTL) specific for human T cell leukemia virus type I (HTLV-I) from peripheral blood lymphocytes (PBL) of a patient with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), an HTLV-l-carrler with Sjögren syndrome, and an asymptomatic HTLV-l-carrier, by repeated stimulation with autologous HTLV-I-Infected T cells . CTL derived from the patient with HAM/TSP expressed CD8 antigen, and their function was restricted by HLA-A2. They showed cytotoxic effects predominantly against the target cells expressing HTLV-I p40 among the autologous B cell lines Infected with vaccinia recombinants containing various HTLV-I genes which served as targets. These data are consistent with the previously reported findings that fresh PBL of HAM/TSP patients contain p40-specific CTL activity. Furthermore, CTL derived from the patient with Sjögren syndrome without neurological involvement also demonstrated cytotoxicity predominantly to p40. The cytotoxicity to the target cells experimentally expressing p40 was blocked by unlabeled HTLV-I-infected cells possessing HLA-A2. HTLV-l-specific cytotoxicity was also Inhibited by unlabeled B cells bearing p40. Thus, HTLV-I p40-specific cytotoxicity is mediated by the major CTL population activated by native HTLV-I antigens in patients with HAM/TSP or Sjögren syndrome. In contrast to the CTL of these patients, CTL similarly Induced from the asymptomatic HTLV-l-carrier, which were highly cytotoxic to autologous HTLV-l-infected T cells, did not show significant levels of cytotoxicity to autologous B cells expressing p40. These CTL possessed CD4 antigen. It was concluded that the predominant CTL population activated by HTLV-I stimulation differs in phenotype and antigen-specificity among HTLV-I seropositive individuals, and that these differences in CTL response may play a role in determining the susceptibility of the host to various HTLV-I related disorders. [ABSTRACT FROM PUBLISHER]

Two Iranian patients with chronic progressive spastic paraparesis and urinary dysfunction were referred to our hospital with the presumptive diagnosis of multiple sclerosis (MS). Routine CSF analysis and magnetic resonance imaging of the two patients were only partially characteristic of MS. Testing for antibodies to human T-cell leukemia virus type I [HTLV-1] in serum using a radioimmune precipitation assay revealed antibodies to HTLV-I in both patients. The infection with HTLV-I was confirmed by polymerase chain reaction (PCR) and liquid hybridization analysis using primers to the tax/rex region and a corresponding probe, demonstrating proviral DNA in peripheral blood mononuclear cells of both patients. On the basis of these findings demonstrating the presence of proviral HTLV-1 DNA in the two Iranian patients, the initial diagnosis of MS was corrected to that of HTLV-I-associated myelopathy (HAM). In contrast, several patients with definite MS (nine from Germany, two from Iran) with a relapsing and remitting form of the disease were tested for HTLV-1 infection by enzyme-linked immunosorbent assay and PCR, which yielded negative results. However, the mother of one HAM patient was found to be infected with HTLV-I. To support an association between HTLV-I infection and CNS disease in the two HAM patients, we analyzed the production of specific IgG antibodies within the CNS based on a simple enzyme immunoassay for viral IgG antibodies in CSF and serum. In the two HAM patients there was significant intrathecal antibody production directed against HTLV-I, but this was not found in any of the samples from MS patients. These findings demonstrate an immune reaction to HTLV-I in the CNS of HAM patients, thus confirming the association of infection and CNS disease. The demonstration of intrathecal HTLV-I antibody production also proved useful for the differential diagnosis of MS or HAM, especially in patients from areas endemic for HTLV-I. [ABSTRACT FROM AUTHOR]

Prosultiamine, a vitamin B1 derivative, has long been used for beriberi neuropathy and Wernicke’s encephalopathy. Based on the finding that prosultiamine induces apoptosis in human T lymphotropic virus type I (HTLV-I)-infected T cells, Nakamura et al. conducted a clinical trial of prosultiamine in patients with HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP). In this open-label, single arm study enrolling 24 HAM/TSP patients recently published in BMC Medicine, oral prosultiamine (300 mg/day for 12 weeks) was found to be effective by neurological, urological and virological evaluations. Notably, it increased detrusor pressure, bladder capacity and maximum flow rate, and improved detrusor overactivity and detrusor-sphincter dyssynergia. A significant decrease in HTLV-I copy numbers in peripheral blood following the treatment provided a rationale for using the drug. The trial has some limitations, such as the small numbers of participants, the open-label design, the lack of a placebo arm, and the short trial period. Nevertheless, the observation that such a safe, cheap drug may have excellent therapeutic effects on HAM/TSP, a chronic devastating illness occurring mainly in developing countries, provides support for future large-scale randomized controlled trials. [ABSTRACT FROM AUTHOR]