A Therapeutic Experience of Rapid Progressive HTLV-1 Associated Myelopathy in a Convalescent Rehabilitation Ward：A Case Report / The Japanese Journal of Rehabilitation Medicine

The patient was a 76-year-old woman who developed involuntary movements in both hands and gait disorder. Weakness in both lower limbs gradually worsened, and she was referred to our hospital. Neurological findings included spastic paraplegia, deep sensory disturbance, sensory ataxia, and bladder and bowel dysfunction. Approximately 4 months after the onset, she became unable to walk independently and had to use a walker. MRI showed a long spinal cord lesion extending from the cervical to thoracic spinal cord. Blood and spinal fluid samples tested positive for anti-human T-cell leukemia virus type 1 (HTLV-1) antibodies. Given these findings and subacute course, she was diagnosed with rapidly progressive HTLV-1 associated myelopathy (HAM). High levels of neopterin and CXCL10 in the cerebrospinal fluid suggested high disease activity；thus, she underwent steroid pulse therapy followed by treatment with maintenance oral prednisolone in our convalescent rehabilitation ward. After approximately 3 months of muscle strength training, mainly for the trunk muscle and the proximal muscle of the lower limbs, and balance exercise, she was able to walk independently and her activities of daily living (ADL) and instrumental ADL (IADL) improved；however, dysuria persisted. The use of clean intermittent self-catheterization instead of indwelling urethral catheter improved her quality of life (QOL). Although rapidly progressive HAM is generally associated with poor prognosis, steroid therapy combined with comprehensive rehabilitation treatment was effective in the present case.

A Therapeutic Experience of Rapid Progressive HTLV-1 Associated Myelopathy in a Convalescent Rehabilitation Ward：A Case Report / The Japanese Journal of Rehabilitation Medicine

The patient was a 76-year-old woman who developed involuntary movements in both hands and gait disorder. Weakness in both lower limbs gradually worsened, and she was referred to our hospital. Neurological findings included spastic paraplegia, deep sensory disturbance, sensory ataxia, and bladder and bowel dysfunction. Approximately 4 months after the onset, she became unable to walk independently and had to use a walker. MRI showed a long spinal cord lesion extending from the cervical to thoracic spinal cord. Blood and spinal fluid samples tested positive for anti-human T-cell leukemia virus type 1 (HTLV-1) antibodies. Given these findings and subacute course, she was diagnosed with rapidly progressive HTLV-1 associated myelopathy (HAM). High levels of neopterin and CXCL10 in the cerebrospinal fluid suggested high disease activity；thus, she underwent steroid pulse therapy followed by treatment with maintenance oral prednisolone in our convalescent rehabilitation ward. After approximately 3 months of muscle strength training, mainly for the trunk muscle and the proximal muscle of the lower limbs, and balance exercise, she was able to walk independently and her activities of daily living (ADL) and instrumental ADL (IADL) improved；however, dysuria persisted. The use of clean intermittent self-catheterization instead of indwelling urethral catheter improved her quality of life (QOL). Although rapidly progressive HAM is generally associated with poor prognosis, steroid therapy combined with comprehensive rehabilitation treatment was effective in the present case.

Co-expression of HBZ, TAX and FOXp3 and HTLV-1-associated myelopathy/tropical spastic paraparesis development in HTLV-1-infected individuals: A systematic review

Human T-cell lymphotropic virus type 1 (HTLV-1) is associated with the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It has been reported that the HTLV-1 proteins (specifically TAX and HBZ) can modulate FOXp3, resulting in an immune imbalance that can favor the progression of HAM/TSP. This review aims to summarize the literature in order to clarify the relationship between the expression of HTLV-1 mRNAs and/or viral proteins (TAX and HBZ) with the expression of mRNA and/or protein FOXp3 and their correlation with HAM/TSP development. This systematic review was conducted according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. The search strategy was performed on the Medical Literature Analysis and Retrieval System Online and Latin American and Caribbean Literature in Health Sciences Platform using subject descriptors. After screening, six articles were included in this review. The studies suggested that TAX and HBZ have a directly proportional correlation with FOXp3 in individuals with HAM/TSP, which also presented an increased expression of FOXp3 compared to asymptomatic controls and/or healthy donors. This systematic review indicates that TAX and HBZ can interact with FOXp3 and that interaction may influence HAM/TSP development.

Neurologic complications of HTLV-1: a review / Complicações neurológicas do HTLV: uma revisão HTLV-1

The human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that infects about 20 million people worldwide and causes immune-mediated diseases of the nervous system. The classical neurological presentation of HTLV-1 infection is the so-called HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). However, HAM/ TSP is not the only neurological outcome that can result from HTLV-1 infection. In this Review it is made an update on the many aspects of this important neurological condition, the HTLV-1 neurological complex.

O vírus linfotrópico de células T humanas tipo 1 (HTLV-1) é um retrovírus que infecta cerca de 20 milhões de pessoas em todo o mundo e causa doenças imunomediadas do sistema nervoso. A apresentação neurológica clássica da infecção pelo HTLV-1 é a chamada paraparesia espástica tropical / mielopatia associada ao HTLV-1 (HAM/TSP). HAM / TSP,no entanto, não é o único desfecho neurológico que pode resultar da infecção pelo HTLV-1. Nesta revisão, é feita uma atualização sobre vários aspectos desta importante condição neurológica, o complexo neurológico do HTLV-1.

Significance and potential of self-management research for HTLV-1 associated myelopathy: review of self-management for people with multiple sclerosis / Journal of Rural Medicine

Objective and Methods: A total of 21 published studies on self-management for people with multiple sclerosis (MS) were reviewed to explore the significance and potential of self-management for people with HTLV-1 associated myelopathy (HAM). These studies were classified based on three concepts: self-management regimen and preferences, context of self-management, and outcomes of self-management.Results: Self-management regimens for people with MS include medical, role, and emotional management. Moreover, self-management regimens are closely associated with the context of self-management, emphasizing the importance of investigating contextual factors and regimens concurrently. Quality of life (QOL) has been evaluated as an outcome of self-management, and self-management has been shown to have both positive and negative effects on the QOL of people with MS. However, insufficient studies focus on self-management regimens and patient preferences; further investigation is necessary to develop effective self-management interventions that reflect the often unique nature of the disease for each individual. The characteristics of HAM are also unique to individual patients. Therefore, investigation of people with HAM in particular is required.Conclusion: This literature review examined the significance of investigating self-management for people with HAM.

Human T-cell lymphotropic virus-1 infection: three infected generations in the same family

Abstract The human T-cell lymphotropic virus-1 (HTLV-1) affects worldwide population; the estimated number of currently infected individuals is 10-20 million. In this report, we describe the clinical findings of three family members with vertical transmission of HTLV-1. This case report highlights the importance of healthcare providers who have optimal knowledge about HTLV-1 including its transmission and pertinent attributes, and who are able to provide affected individuals with adequate information regarding their condition.

Standardisation of Western blotting to detect HTLV-1 antibodies synthesised in the central nervous system of HAM/TSP patients

Intrathecal synthesis of human T-lymphotropic virus type 1 (HTLV-1) antibodies (Abs) represents conclusive evidence of a specific immune response in the central nervous system of HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients. Western blotting (WB) for HTLV Abs in serum is a confirmatory test for HTLV-1 infection. The aim of this study was to standardise the Western blot to demonstrate the intrathecal pattern of Abs against HTLV-1 proteins in HAM/TSP patients. Paired cerebrospinal fluid (CSF) and serum samples were selected from 20 patients with definite HAM/TSP, 19 HTLV-1 seronegative patients and two HTLV-1 patients without definite HAM/TSP. The presence of reactive bands of greater intensity in the CSF compared to serum (or bands in only the CSF) indicated the intrathecal synthesis of anti-HTLV-1 Abs. All definite HAM/TSP patients presented with an intrathecal synthesis of anti-HTLV-1 Abs; these Abs were not detected in the control patients. The most frequent intrathecal targets of anti-HTLV-1 Abs were GD21, rgp46-I and p24 and, to a lesser extent, p19, p26, p28, p32, p36, p53 gp21 and gp46. The intrathecal immune response against env (GD21 and rgp46-I) and gag (p24) proteins represents the most important humoral pattern in HAM/TSP. This response may be used as a diagnostic marker, considering the frequent association of intrathecal anti-HTLV-1 Ab synthesis with HAM/TSP and the pathogenesis of this neurological disease.

HAM/TSP: association between white matter lesions on magnetic resonance imaging, clinical and cerebrospinal fluid findings / HAM/TSP: associação entre lesões de substância branca à ressonância magnética, achados clínicos e do líquido cefalorraquidiano

OBJECTIVE: To investigate the association between clinical data, white matter lesions and inflammatory cerebrospinal fluid (CSF) findings in HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). METHOD: We studied brain and cervical spinal cord on magnetic resonance imaging (MRI) and CSF examinations of 28 Brazilian HAM/TSP patients. RESULTS: The majority of patients had severe neurological incapacity with EDSS median of 6.5 (3-8). The brain MRI showed white matter lesions (75%) and atrophy (14%). The preferential brain location was periventricular. Cervical demyelination lesions occurred in 11% of the cases, and cervical atrophy in 3.5%. One patient had enhancement lesions on T1 cervical spinal cord MRI. Cases with spinal cord lesions had signs of acute CSF inflammation. The brain white matter lesions predominated in the patients with higher age. CONCLUSION: Our data suggest that an active inflammatory process is associated with the cervical spinal cord lesions in HAM/TSP. The brain abnormalities are not related to the clinical picture of HAM/TSP.

OBJETIVO: Analisar a associação entre aspectos clínicos, lesões de substância branca e reação inflamatória aguda no líquido cefalorraquidiano (LCR) na mielopatia associa ao HTLV-1 (HAM/TSP). MÉTODO: Foram estudadas ressonâncias magnéticas (RM) do encéfalo/medula espinhal cervical e exame do LCR de 28 pacientes com HAM/TSP. RESULTADOS: A maioria dos pacientes apresentava grave incapacidade neurológica, com EDSS 6,5 (3-8). A RM revelou lesões da substância branca (75%) com predominância periventricular e atrofia cortical (14%). Lesões desmielinizantes cervicais ocorreram em 11% dos casos e atrofia em 3,5%. Um paciente apresentou lesão cervical na T1 com captação de contraste. Sinais de inflamação aguda no LCR ocorreram em situações de lesão da medula espinhal cervical. As alterações de substância branca do encéfalo predominaram nos indivíduos com maior faixa etária. CONCLUSÃO: Nossos achados sugerem que processo inflamatório com atividade clínica na HAM/TSP está associado a lesões da medula espinhal cervical. As anormalidades da substância branca encefálicas não são relacionadas ao quadro clínico de HAM/TSP.

In vivo fluctuation of Tax, Foxp3, CTLA-4, and GITR mRNA expression in CD4+CD25+ T cells of patients with human T-lymphotropic virus type 1-associated myelopathy

HTLV-1 Tax expression exerts an inhibitory effect on the Foxp3 transcription factor in CD4+CD25+ T-regulatory cells (Treg). For a better understanding of the role of Tax mRNA in the gene expression of cellular markers we measured Tax, Foxp3, CTLA-4, GITR, TGF-β, and IL-10 mRNA in Treg cells of 50 patients with human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP; 27 women and 23 men; mean age: 56.7 years). The control group consisted of 23 non-infected subjects (12 women and 11 men) with a mean age of 51.3 years. Real-time PCR was used to measure mRNA of Tax proteins and several cellular markers of Treg function. Determinations revealed a high level of Tax mRNA in HAM/TSP (124.35 copies/100 CD4+CD25+ T cells). Foxp3, GITR, and CTLA-4 mRNA levels were lower in HAM/TSP patients (mean ± SD, 22.07 ± 0.78, 9.63 ± 0.36, and 4.54 ± 0.39, respectively) than in non-infected controls (47.15 ± 12.94, 22.14 ± 1.91, and 21.07 ± 2.31). Both groups had similar levels of TGF-β and IL-10. An inverse relationship was found between Tax levels and Foxp3, CTLA-4, and GITR levels. Conversely, there was a direct correlation between levels of Foxp3, GITR, and CTLA-4. Disease severity and evolution time did not correlate with Tax or Foxp3 levels. The present results suggest that Tax and Foxp3 mRNA vary with the same degree of disease severity in HAM/TSP patients. Tax fluctuations may affect CTLA-4 and GITR expression via the Foxp3 pathway, causing virus-induced dysfunction of CD4+CD25+ T cells in HAM/TSP patients.

Efficacy of Rehabilitation for Patients with HAM (HTLV-1 associated myelopathy) / The Japanese Journal of Rehabilitation Medicine

The effectiveness of rehabilitation in patients with HTLV-1associated myelopathy (HAM) was evaluated. The HAM patient is characterized by chronic progressive spastic paraplegia with dysuria and muscular weakness of the lower trunk, as well as the pelvic and hip muscles. However, the muscular strength of the lower limbs and feet is relatively well maintained. The 12 subjects enrolled in this study included 2 men and 10 women. Their average age was 53.2 years, their average duration of disease was 20.5 years, and they were involved in training for an average of 41 days. The rehabilitation program involved muscular strength training of the lower trunk, pelvic, and hip muscles. After all patients completed the rehabilitation program, a significant improvement was seen in the truncal flexors, the truncal extensors, and the truncal rotators in the lower trunk. As for the hip muscles, a significant improvement was seen in the iliopsoas, the gluteus maximus, and the gluteus medius. The improvement was evaluated using Osame's Motor Disability Score (OMDS), the Functional Independence Measure (FIM) and the Barthel Index. The patients' improvements in motor function and ADL suggest that rehabilitation was effective.

Estudo clínico controlado randomizado aberto com metilprednisolona na mielopatia associada ao vírus tipo 1 linfotrópico de células T humanas/paraparesia espástica tropical / Clinical controlled randomized open trial with methylprednisolone in human T linphotropic virus type 1 associated/myelopathy and tropical spastic paraparesis

Introdução. Doença associada ao vírus tipo 1 linfotrópico de células T humanas ou paraparesia espástica tropical é uma mielopatia caracterizada por início insidioso, com fraqueza nas extremidades dos membros inferiores, seguida por espasticidade e ou hiperreflexia global, disfunção esfincteriana vesical e intestinal e perda sensorial variável. Objetivo. Avaliar a eficácia do tratamento com metilprednisolona em altas doses, em relação ao tempo de evolução e apresentação clínica de pacientes com a doença. Método. Estudou-se a avaliação clínica de longo termo (t = 24 meses) da resposta de treze pacientes com diagnóstico precoce do quadro ao tratamento com metilprednisolona em esquema mensal de administração (1 g/dia por três dias), por seis meses consecutivos, com atendimento em hospital-dia. Foi realizado o acompanhamento dos pacientes, usando-se como parâmetros as escalas de critérios clínicos de Osame e Kurtzke, e comparou-se com um grupo-controle pareado por sexo, idade e quadro clínico (n = 13), que não recebeu esse tipo de tratamento. Resultados. O resultado do teste estatístico de Mann-Whitney para o índice final das escalas de Osame e Kurtzke foi p = 0,1688 (Delta t = 24 meses). Aplicou-se novamente o teste estatístico de Mann-Whitney às diferenças entre o índice final e inicial das escalas citadas acima, que resultou em p = 0,0154. O intervalo de confiança foi 95%, médiade 0,18 a 1,37. O qui ao quadrado (Yates, corrigido) foi 0,28. O risco relativo foi 0,5. Conclusão. Não houve diferença na manutenção do grau de incapacidade entre o grupo experimental e o grupo de controle. A fisioterapia foi um fator de proteção à estabilidade do grau de incapacidade entre os pacientes com a mielopatia em estudo.

Background. Human T linphotropic virus type 1 associated with myelopathy or tropical spastic paraparesis is a myelopathy characterized by insidious onset with weakness in the extremities of the inferior members, followed by spasticity, global hiperreflexy and dysfunction sensorial loss. Objective. The aim was to study the treatment with methylprednisolone in high doses, in relation to the time of evolution and presentation of the disease and its effectiveness. Methods. We studied the long term clinical response of patients with early diagnoses of human T linphotropic virus type 1 associated with myelopathy or tropical spastic paraparesis to treatment with methylprednisolone in a monthly scheme of administration (1 g/day for three days) for six months. The patients were followed during 24 months using as parameters the scales of clinical criteria by Osame and Kurtzke and compared with a control group of patients who did not receive this treatment type. Results. Mann-Whitney for the final score is p = 0.1688 (delta t = 24 months) and Mann-Whitney for the differences between the final and the initial scores is p = 0.0154. Confidence interval of 95% ranged from 0.18 to 1.37. Chi-square (Yates, corrected) was 0.28. Relative risk was 0.5. Conclusion. There is no difference in the maintenance of the degree of disability between experimental group and control group. The physiotherapy is a protection factor for the stability of the degree of disability among patients with the disease.

High HTLV-1 proviral load, a marker for HTLV-1 associated myelopathy/tropical spastic paraparesis, is also detected in patients with infective dermatitis associated with HTLV-1

Salvador (BA, Brazil) is an endemic area for human T-cell lymphotrophic virus type 1 (HTLV-1). The overall prevalence of HTLV-1 infection in the general population has been estimated to be 1.76%. HTLV-1 carriers may develop a variety of diseases such as adult T-cell leukemia/lymphoma, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and infective dermatitis associated with HTLV-1 (IDH). IDH is a chronic and severe form of childhood exudative and infective dermatitis involving mainly the scalp, neck and ears. It has recently been observed that 30% of patients with IDH develop juvenile HAM/TSP. The replication of HTLV-1 has been reported to be greater in adult HAM/TSP patients than in asymptomatic HTLV-1 carriers. In the current study, the proviral load of 28 children and adolescents with IDH not associated with HAM/TSP was determined and the results were compared to those obtained in 28 HTLV-1 adult carriers and 28 adult patients with HAM/TSP. The proviral load in IDH patients was similar to that of patients with HAM/TSP and much higher than that found in HTLV-1 carriers. The high levels of proviral load in IDH patients were not associated with age, duration of illness, duration of breast-feeding, or activity status of the skin disease. Since proviral load is associated with neurological disability, these data support the view that IDH patients are at high risk of developing HAM/TSP.

Frequent HTLV-1 infection in the offspring of Peruvian women with HTLV-1-associated myelopathy/tropical spastic paraparesis or strongyloidiasis

OBJECTIVES: To describe the frequency of HTLV-1 infection among offspring of mothers who had presented with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), strongyloidiasis, or asymptomatic HTLV-1 infection, and to identify factors associated with HTLV-1 infection. METHODS: In a descriptive study, records were reviewed of HTLV-1-positive women and their offspring who had been tested for HTLV infection at a public hospital in Lima, Peru, from 1989 to 2003. Sons and daughters of women who had presented with strongyloidiasis, HAM/TSP, or asymptomatic infection were eligible for this study. RESULTS: Three hundred seventy subjects were included: 279 were the offspring of 104 mothers presenting with HAM/TSP, 58 were the offspring of 22 mothers with strongyloidiasis, and 33 were the offspring of 26 asymptomatic mothers. Mean age of the offspring at the time of testing was 26 years (standard deviation 12). Nineteen percent of the offspring tested positive for HTLV-1: 6 percent (2/33) of those with asymptomatic mothers, 19 percent (52/279) among the offspring of mothers with HAM/TSP, and 31 percent (18/58) among the offspring of mothers presenting with strongyloidiasis On multiple logistic regression analysis, three factors were significantly associated with HTLV-1: (a) duration of breast-feeding (odds ratio [OR] = 15.1; [4.2-54.1] for 12 to 24 months versus less than 6 months breast-feeding); (b) clinical condition of the mother (OR = 8.3 [1.0-65.3] for HAM/TSP and OR = 11.5 [1.4-98.4] for strongyloidiasis in comparison with offspring of asymptomatic mothers); and (c) transfusion history (OR = 5.5 [2.0-15.2]). CONCLUSIONS: In addition to known risk factors for HTLV-1 transmission (duration of breast-feeding and history of blood transfusion), maternal HAM/TSP and strongyloidiasis were associated with seropositivity among offspring of HTLV-1-infected mothers.

OBJETIVOS: Describir la frecuencia de la infección por HTLV-1 en los hijos e hijas de madres diagnosticadas con mielopatía/paraparesia espástica tropical asociada con el HTLV-1 (M/PET-HTLV-1), estrongiloidiasis o infección asintomática por HTLV-1, e identificar los factores asociados con la infección por HTLV-1. MÉTODOS: Para este estudio descriptivo se revisaron los registros de mujeres positivas a HTLV-1 y de sus hijos evaluados con pruebas para la infección por HTLV en un hospital público de Lima, Perú, entre 1989 y 2003. Eran elegibles para este estudio los hijos y las hijas de las mujeres que se presentaron con estrongiloidiasis, M/PET-HTLV-1 o infección asintomática. RESULTADOS: En el estudio participaron 370 personas: 279 hijos de 104 madres con M/PET-HTLV-1, 58 hijos de 22 madres con estrongiloidiasis y 33 hijos de 26 madres asintomáticas. La edad promedio de los participantes en el momento de su prueba para HTLV era de 26 años (desviación estándar: 12 años). De las personas estudiadas, 19 por ciento resultaron positivas a la infección por HTLV-1: 6 por ciento (2/33) de los hijos de madres asintomáticas, 19 por ciento (52/279) de los hijos de madres con M/PET-HTLV-1 y 31 por ciento (18/58) de los hijos de madres con estrongiloidiasis. Según el análisis de regresión logística múltiple, tres factores se asociaron significativamente con la infección por HTLV-1: a) duración de la lactancia materna por 12_24 meses (razón de posibilidades [odds ratio, OR] = 15,1; intervalo de confianza de 95 por ciento [IC95 por ciento]: 4,2 a 54,1, frente a la lactancia materna por menos de 6 meses); b) que la madre presentara M/PET-HTLV-1 o estrongiloidiasis (OR = 8,3; IC95 por ciento: 1,0 a 65,3 y OR = 11,5; IC95 por ciento: 1,4 a 98,4, respectivamente, en comparación con los hijos de madres asintomáticas); y c) los antecedentes de haber recibido una transfusión sanguínea (OR = 5,5; IC95 por ciento: 2,0 a 15,2). CONCLUSIONES: Además de los factores...