Tropical spastic paraparesis

热带痉挛性轻瘫
  • 文章类型: Case Reports
    人T细胞白血病病毒1型(HTLV-1)可引起HTLV-1相关性脊髓病/热带痉挛性轻瘫(HAM/TSP)。HAM/TSP的当前治疗选择有限。我们提出了一个女性快速进展的HAM/TSP与显著,持续的临床改善后开始霉酚酸酯(MMA)。患者外周血单核细胞,她的无症状携带者丈夫和8名健康对照者被隔离。使用流式细胞术和CSFE增殖测定分析了暴露于低和高MMA浓度时T细胞群的频率和增殖差异。T细胞功能和增殖的表征显示HTLV-1+供体中更高水平的GranzymeB。MMA开始后,该患者HAM/TSP症状的改善和稳定性需要进一步研究作为HAM/TSP的潜在治疗方法。
    Human T-cell leukemia virus type 1 (HTLV-1) can cause HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP). Current treatment options for HAM/TSP are limited. We present a woman with rapidly-progressive HAM/TSP with significant, sustained clinical improvement following initiation of mycophenolate mofetil (MMA). Peripheral blood mononuclear cells from the patient, her asymptomatic carrier husband and eight healthy controls were isolated. Frequencies of T-cell populations upon exposure to low and high MMA concentrations and differences in proliferation were analyzed using flow cytometry and a CSFE-proliferation assay. Characterization of T-cell function and proliferation showed higher levels of GranzymeB in HTLV-1+ donors. The improvement and stability of symptoms in this patient with HAM/TSP following MMA initiation requires further study as a potential treatment for HAM/TSP.
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  • 文章类型: Journal Article
    HTLV-1是两种重要的疾病,HAM/TSP和ATLL。全世界大约有1000万到2000万人感染了HTLV-1。识别不同癌症中改变的基因对于找到潜在的治疗策略至关重要。RAS/MAPK信号通路的蛋白之一是MEK1,其由MAP2K1基因制成。MAP2K1基因对MAPK信号通路的影响尚未完全阐明。本研究旨在确定与健康个体相比,ATLL患者的MAP2K1基因突变和MAP2K1基因表达水平。
    本研究调查了10名ATLL和10名健康对照个体。我们使用ELISA测试来筛选抗HTLV-I抗体,并使用PCR来确认感染。然后,我们从新鲜的全血中提取总RNA,并合成了cDNA。通过qRT-PCR检测MAP2K1基因的表达水平,并检查MAP2K1基因中可能的突变;所有样品均通过BioEdite软件进行测序和分析。
    ATLL组MAP2K1基因表达显著高于健康对照组(P=0.001)。突变测序分析显示核苷酸212(S→R)变化和不同核苷酸处的鉴定突变,其与UniProt数据库中定义的核苷酸突变完全不同。
    这些结果可能是预防的视角,预后,MAP2K1基因在疾病的靶向治疗中起着至关重要的作用。
    UNASSIGNED: 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.
    UNASSIGNED: 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.
    UNASSIGNED: 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.
    UNASSIGNED: These results could be a perspective in the prevention, prognosis, and targeted treatment of diseases in which the MAP2K1 gene plays a vital role.
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  • 文章类型: Journal Article
    围产期既是一个高度脆弱的阶段,也是一个人口健康状况的重要指标。由于人类T细胞白血病病毒1型(HTLV-1)的不良健康影响,其传播的兴趣正在增加。然而,对健康规划重要的HTLV-1的全国代表性数据无法用于该亚人群.这项研究旨在对尼日利亚孕妇的HTLV-1患病率进行汇总估计,以量化其临床负担和公共卫生影响。本系统评价是根据2020年系统评价和荟萃分析的首选报告项目进行的。在对尼日利亚文献进行系统回顾之后,12项研究(2821名孕妇或产后妇女)被纳入最终证据综合。通过酶联免疫吸附试验进行阳性筛查后,尼日利亚围产期妇女的估计HTLV-1患病率为5.44%(95%置信区间[CI],3.16-9.20%)。对两个主要地区的亚组分析显示,西部地区与南部地区的患病率略高(5.55%[95%CI,2.49-11.87%];4.91%[95%CI,2.11-11.02];P=0.84)。然而,按地缘政治地区进行的亚组分析显示,尼日利亚西南部和西北部的患病率最高(9.23%[95%CI,4.35-18.55;I2,93%]和7.15%[95%CI,1.54-27.54];I2,92%).我们十年前的亚组分析发现HTLV-1患病率不一致。此外,我们的文献综述显示,在各种临床类型的淋巴瘤/白血病和脊髓病患者中,HTLV感染率为2-22%.这些发现对确定尼日利亚HTLV-1感染的流行病学模式具有重要意义。他们还表明,在低流行区附近存在HTLV流行簇,即使在相同的地缘政治区内。
    BACKGROUND: The peripartum period is both a highly vulnerable stage and a significant indicator of a population\'s health status. Interest is increasing in human T-cell lymphotropic virus type-1 (HTLV-1) transmission due to its adverse health impacts. However, nationally representative data on HTLV-1 that are important for health planning are unavailable for this subpopulation.
    OBJECTIVE: This study aimed to conduct a pooled estimate of HTLV-1 prevalence among pregnant women in Nigeria to quantify its clinical burden and public health implications.
    METHODS: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020 statement.
    RESULTS: After a systematic review of the Nigerian literature, 12 studies (2,821 pregnant or postnatal women) were included in the final evidence synthesis. The estimated HTLV-1 prevalence in Nigerian peripartum women following a positive screening test by enzyme-linked immunosorbent assay was 5.44% (95% confidence interval [CI], 3.16%-9.20%). A subgroup analysis of the 2 major regions showed a slightly higher prevalence in the Western versus Southern region (5.55% [95% CI, 2.49%-11.87%]; and 4.91% [95% CI, 2.11%-11.02%]; P=0.84). However, a subgroup analysis by geopolitical zone revealed that Southwestern and Northwestern Nigeria had the highest prevalence (9.23% [95% CI, 4.35%-18.55%; I2=93%] and 7.15% [95% CI, 1.54%-27.54%]; I2=92%). Our decade-old subgroup analysis found inconsistencies in the HTLV-1 prevalence. Furthermore, our literature review revealed a prevalence of HTLV infection among patients with various clinical types of lymphomas/leukemias and myelopathy of 2%-22%.
    CONCLUSIONS: These findings have important implications in defining the epidemiological patterns of HTLV-1 infection in Nigeria. They also suggest the presence of HTLV-endemic clusters near low-endemic areas, even within the same geopolitical zones.
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  • 文章类型: Journal Article
    (1)背景:与I型人类T细胞淋巴病毒(HTLV-1)相关的热带痉挛性轻瘫(TSP/HAM)是一种缓慢的,慢性,和导致平衡变化的进行性疾病。TSP/HAM诊断可以分类为可能,可能,和确定。我们比较了不同TSP/HAM诊断的HTLV-1感染患者的静态平衡控制。(2)方法:我们的样本包括13名感染HTLV-1的参与者和16名健康参与者。使用睁眼和闭眼的力平台记录压力中心。我们把录音分成三个间隔,周期T1(对应于前10秒);周期T2(从10到45秒);周期T3(从45到55秒)。(3)结果:八名感染HTLV-1的参与者被分类为可能的TSP/HAM,五名感染HTLV-1的参与者被分类为确定的TSP/HAM。考虑到身体摇摆的结构和全局变量,与对照组和可能的TSP/HAM相比,患有明确PET/MAH的患者的姿势不稳定性显着增加。(4)结论:我们得出结论,平衡的严重程度与TSP/HAM的体征和症状的程度直接相关。
    (1) Background: Tropical spastic paraparesis (TSP/HAM) associated with the T cell lymphotropic virus in type I humans (HTLV-1) is a slow, chronic, and progressive disease that causes balance changes. TSP/HAM diagnosis can be classified as probable, possible, and definite. We compared the static balance control of HTLV-1-infected patients with different TSP/HAM diagnosis. (2) Methods: Our sample consisted of 13 participants infected with HTLV-1 and 16 healthy participants. The center of pressure was recorded using a force platform with open and closed eyes. We divided the recordings into three intervals, period T1 (corresponds to the first 10 s); period T2 (from 10 to 45 s); period T3 (from 45 to 55 s). (3) Results: Eight participants infected with HTLV-1 were classified as probable TSP/HAM and five participants infected with HTLV-1 were classified as definite TSP/HAM. There was a significant increase in postural instability in patients with definite PET/MAH considering the structural and global variables of body sway compared to the control and the probable TSP/HAM. (4) Conclusions: We concluded that the severity of balance is directly related to the degree of signs and symptoms of TSP/HAM.
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  • 文章类型: Journal Article
    在HTLV-1相关脊髓病(HAM/TSP)中发现的脑白质病变的起源仍未定义。我们调查了HAM/TSP中白质病变与心血管危险因素之间的关系。40例HAM/TSP患者包括60%的女性,平均年龄为58.6±8岁。10年心血管疾病的可能性很低,为53%,中等在38%,在10%的患者中很高。HAM/TSP患者有无脑损害的心血管危险因素之间无差异(p>0.05)。我们的数据表明,脑白质异常与HAM/TSP的心血管风险增加无关。
    The origin of brain white matter lesion found in HTLV-1-associated myelopathy (HAM/TSP) remains undefined. We investigated the association between white matter lesions in HAM/TSP with cardiovascular risk factors. The group of 40 patients with HAM/TSP included 60% females and mean age of 58.6 ± 8 years old. The probability of 10-year cardiovascular disease was low in 53%, moderate in 38%, and high in 10% of the patients. There was no difference between the cardiovascular risk factors in HAM/TSP patients with and without brain lesions (p > 0.05). Our data suggest that the brain white matter abnormalities are not associated to increased cardiovascular risk in HAM/TSP.
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  • 文章类型: Journal Article
    To verify brain and spinal changes using magnetic resonance imaging in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis. This was a systematic review. The descriptors used were tropical spastic paraparesis and magnetic resonance image. The keyword HTLV-1-associated myelopathy was also used. Twenty-three articles were included: 16 detected brain changes and 18 detected spinal changes. White matter lesions were the most frequent finding in the brain. Brain injuries were most frequently identified in the periventricular region, in the subcortical region, in the centrum semiovale, in the brain stem, and corpus callosum. Atrophy was the most frequent finding of the spinal cord, affecting the thoracic and cervical regions, and was associated with a longer evolution of myelopathy. White matter lesions in these regions were also observed. Cortical white matter lesions and thoracic spinal cord atrophy were the most frequently reported changes in patients with HTLV-1-associated myelopathy.
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  • 文章类型: Case Reports
    在这种情况下,妊娠与HAM恶化无关,也与不良妊娠结局无关。这些发现表明,患有HAM/TSP的女性,即使是那些使用轮椅的人,不应该阻止怀孕。
    Pregnancy was not associated with deterioration of HAM nor was HAM associated with adverse pregnancy outcome in this case. These findings suggest that women with HAM/TSP, even those who use a wheelchair, should not be discouraged from pregnancy.
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  • 文章类型: Case Reports
    背景:神经源性膀胱过度活动症是人类T细胞白血病病毒1型相关脊髓病/热带痉挛性轻瘫的主要特征。我们成功地对人T细胞白血病病毒1型相关脊髓病/热带痉挛性轻瘫引起的难治性神经源性膀胱过度活动症进行了膀胱腔内胃泌素毒素A治疗。
    方法:我们回顾性回顾了4例神经源性膀胱过度活动症患者,这些患者患有人类T细胞白血病病毒1型相关脊髓病/热带痉挛性轻瘫,他们在2020年4月至10月期间接受了膀胱壁注射甲abotulintoxinA。所有患者均为女性。他们的平均年龄是66岁(范围,63-71)年。他们以前单独或联合使用β3-肾上腺素能受体激动剂或抗胆碱能药物治疗≥12周。然而,获得了不足的结果。经过4周的膀胱腔内注射毒素A治疗,在所有情况下,膀胱过度活动症症状得到改善,最大膀胱容量增加。
    结论:膀胱内胃泌素毒素A治疗可用于治疗人T细胞白血病病毒1型相关脊髓病/热带痉挛性轻瘫所致的难治性膀胱过度活动症。
    BACKGROUND: Neurogenic overactive bladder is a main feature of human T-cell leukemia virus type 1-associated myelopathy/tropical spastic paraparesis. We successfully performed intravesical onabotulinumtoxinA therapy for refractory neurogenic overactive bladder due to human T-cell leukemia virus type 1-associated myelopathy/tropical spastic paraparesis.
    METHODS: We retrospectively reviewed four neurogenic overactive bladder patients with human T-cell leukemia virus type 1-associated myelopathy/tropical spastic paraparesis who underwent bladder wall injections of onabotulinumtoxinA from April to October 2020. All patients were female. Their median age was 66 (range, 63-71) years. They were previously treated with β3-adrenergic receptor agonists or anticholinergic drugs alone or in combination for ≥12 weeks. However, insufficient results were obtained. After 4 weeks of intravesical onabotulinumtoxinA therapy, overactive bladder symptoms improved and maximum cystometric capacity increased in all cases.
    CONCLUSIONS: Intravesical onabotulinumtoxinA therapy may be useful for treating refractory overactive bladder due to human T-cell leukemia virus type 1-associated myelopathy/tropical spastic paraparesis.
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  • 文章类型: Journal Article
    The association between high proviral load (PVL) in peripheral blood mononuclear cells (PBMC), cognitive disturbance and white matter brain lesions in HTLV-1-infected individuals is still undefined. A cross-sectional study included 62 participants: 22 asymptomatic carriers (mean age 43.4 ± 13.1 years old), 22 patients with HTLV-1-associated myelopathy (HAM/TSP) (mean age 51.5 ± 8.7 years old), and 18 uninfected controls (mean age 52.3 ± 11.1 years old). All individuals fulfilled the following criteria: between 18 and 65 years of age, more than 4 years of formal education, and completed neuropsychological evaluation and HTLV-1 serology. Infected individuals underwent brain conventional magnetic resonance imaging and PVL quantitative PCR (qPCR). Statistical analysis was adjusted in the models by age and education. Cognitive deficit was observed in all groups. Patients with HAM/TSP showed higher neurocognitive deviation in attention and motor skills, higher frequency (84%) of brain white matter lesions, and higher PVL median (range) 8.45 (0.5-71.4) copies/100 PBMC. Brain white matter lesion was associated with verbal memory deficit in HTLV-1-infected individuals (HAM/TSP and asymptomatic carriers) (p = 0.026). In addition, there was a correlation between higher PVL and neurocognitive dysfunction score (processing speed of visuomotor information and visuoconstructive praxis) in HTLV-1-infected patients. The study demonstrates an association between HTLV-1 infection, neurocognitive disorder, and white matter brain lesions on MRI as well as a correlation with higher HTLV-1 PVL, suggesting that the central nervous system involvement by HTLV-1 is not restricted to the spinal cord but involves the whole neuro-axis. HTLV-1-infected individuals should be tested for cognitive impairment.
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  • 文章类型: Journal Article
    In the logic of integrality in health, one of the aspects less addressed by assistance services is the question of spirituality. This study utilized qualitative analysis from focus groups to identify whether spirituality can contribute to coping with problems arising from the HTLV-1 myelopathy associated or tropical spastic paraparesis (HAM/TSP). The testimonies were recorded and then transcribed. The information was then systematized by the analysis of thematic-categorical content. When giving voice to people who suffer from HAM/TSP, there is clear evidence that spirituality, understood broadly and not restricted to institutionalized religious practices, is expressed in narratives of feeling for others and trust in God. Through spiritual solutions, people with HAM/TSP find the strength to face their disability and pain.
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