Demyelinating

脱髓鞘
  • 文章类型: Journal Article
    本体感觉和触觉受损的远端关节发育不良(DAIPT)是一种常染色体隐性遗传性神经遗传疾病,由PIEZO2基因中的纯合致病变异引起。在这里,我们介绍了四个阿曼家庭,其中有多个受影响的成员患有DAIPT。基因诊断是通过全外显子组测序建立的,我们确定了一个以前未报道的纯合错义变体PIEZO2:c.1591T>C,P.(Trp531Arg)在一个有两个受影响成员的家庭中。所有患者均在出生后不久出现临床表现,包括短暂性呼吸功能不全,显著的低张力,和认知功能保留的粗大运动发育迟缓。正如我们在老年患者中所看到的那样,随着年龄的增长,包括关节病在内的骨骼表现更加明显。该病例报告对于医生和遗传咨询师来说是重要的,可以更快地进行诊断,并作为婚前检测计划的一部分为有风险的家庭成员提供携带者检测。这可以帮助减轻这种疾病的负担。
    Distal arthrogryposis with impaired proprioception and touch (DAIPT) is an autosomal recessive neurogenetic disorder caused by homozygous pathogenic variants in the PIEZO2 gene. Here we present four Omani families with multiple affected members with DAIPT. The genetic diagnosis was established by whole exome sequencing and we identified a previously unreported homozygous missense variant PIEZO2 : c.1591T > C, P.(Trp531Arg) in one family with two affected members. All patients showed clinical manifestation shortly after birth including transient respiratory insufficiency, significant hypotonia, and gross motor developmental delay with preserved cognitive function. The skeletal manifestation including arthrogryposis is more pronounced with age as we saw in our older patient. This case report will be of importance for physicians and genetic counsellors for faster diagnosis and for offering carrier testing for at-risk family members as part of the premarital testing program, which could help in reducing the burden of this disorder.
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  • 文章类型: Case Reports
    视神经脊髓炎谱系障碍(NMOSD)是一种罕见的中枢神经系统疾病,表现为视神经炎,脊髓炎,和脑干综合征。可能是水通道蛋白-4血清阳性,抗髓磷脂少突胶质细胞糖蛋白(MOG)抗体血清阳性,或双血清阴性。双血清阴性NMOSD可能构成诊断和治疗挑战。治疗通常旨在降低复发率,大剂量静脉注射甲基强的松龙是一线药物。非类固醇治疗包括硫唑嘌呤,霉酚酸酯,还有利妥昔单抗.该病例描述了一名45岁的女性,表现为左臂麻木和虚弱三个月。她之前在2013年被诊断为视神经炎,但失去了随访。虚弱的进展需要进入神经科。诊断工作和影像学检查提示视神经脊髓炎。水通道蛋白-4,抗MOG的测试,免疫球蛋白G,脑脊液免疫球蛋白M均为阴性。初始治疗包括甲基强的松龙;然而,由于症状的进展,她接受了两个周期的利妥昔单抗治疗。利妥昔单抗靶向B细胞中的CD20抗原,被认为可以降低复发风险和NMOSD的严重程度。病人的Barthel指数评分,扩展残疾状况量表评分,利妥昔单抗两个周期后,运动检查有所改善。
    Neuromyelitis optica spectrum disorder (NMOSD) is a rare central nervous system disease presenting as optic neuritis, myelitis, and brainstem syndromes. It may be aquaporin-4 seropositive, anti-myelin oligodendrocyte glycoprotein (MOG) antibody seropositive, or double seronegative. Double-seronegative NMOSD can pose a diagnostic and therapeutic challenge. Treatment typically aims to decrease the incidence of relapse, for which high-dose intravenous methylprednisolone is the first-line agent. Non-steroid treatments include azathioprine, mycophenolate mofetil, and rituximab. This case describes a 45-year-old female presenting with left arm numbness and weakness for three months. She had been previously diagnosed with optic neuritis in 2013 but was lost to follow-up. Progression of weakness warranted admission to the neurology department. Diagnostic work and imaging were suggestive of neuromyelitis optica. Tests for aquaporin-4, anti-MOG, immunoglobulin G, and immunoglobulin M in the cerebrospinal fluid were all negative. Initial treatment comprised methylprednisolone; however, due to the progression of symptoms, she was given two cycles of rituximab. Rituximab targets the CD20 antigen in B cells and is thought to reduce the risk of relapse and the severity of NMOSD. The patient\'s Barthel index score, expanded disability status scale score, and motor examination improved after two cycles of rituximab.
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  • 文章类型: Journal Article
    目的:评估儿童发病型多发性硬化(POMS)疾病改善治疗(DMT)开始时间与预后之间的关系。
    方法:回顾性分析来自两个三级转诊儿科神经免疫学诊所的POMS患儿。结果指标包括年度复发率(ARR),MRI病变负荷(T1,T2-FLAIR,和GAD后对比序列),EDSS,和25英尺的步行时间在最新的随访访问。使用线性和逻辑回归模型的单变量和多变量分析用于评估患者特征和结果之间的关联。
    结果:总计,68例患者进行复查。超过一半的患者是女性(62%),32(47%)是西班牙裔/LatinX。诊断时的中位年龄为14.2岁(IQR:11.0-16.5),从诊断到最后一次随访的中位持续时间为2.5年(IQR:1.6-4.6).感官(29.4%),脑干(23.5%),锥体(19.1%)症状最为常见。干扰素β(32.4%),富马酸二甲酯(27.9%)和利妥昔单抗(26.5%)是最常用的一线DMT.患者的平均ARR为0.5(IQR:0.08-0.84),在最近的随访中,EDSS评分为1.0(IQR:0.0-2.0)。DMT启动延迟与较高的ARR(R=0.38,p=0.0016)和较长的25英尺步行时间(R=0.34,p=0.0077)相关。在多变量分析中,延迟DMT仍然是较高ARR(p=0.002)和较长25英尺步行时间(p=0.047)的显著预测因子.延迟DMT开始和使用低/中等功效DMT在最近的随访中预测GAD增强病变(分别为p=0.004和0.019)。
    结论:POMS中DMT启动延迟与不利结果有关,包括更高的ARR和更长的25英尺步行时间。
    OBJECTIVE: To evaluate association between time to initiation of disease modifying treatment (DMT) and outcomes in pediatric-onset Multiple Sclerosis (POMS).
    METHODS: A retrospective analysis of children with POMS from two tertiary referral pediatric Neuroimmunology clinics. Outcome measures comprised annualized relapse rate (ARR), MRI lesion burden (T1, T2-FLAIR, and post-GAD contrast sequences), EDSS, and 25-ft walk duration at the latest follow-up visit. Univariate and multivariate analysis using linear and logistic regression models were used to assess associations between patient characteristics and outcomes.
    RESULTS: In total, 68 patients were reviewed. More than half of patients were female (62 %) and 32 (47 %) were Hispanic/LatinX. Median age at diagnosis was 14.2 years (IQR: 11.0-16.5), and median duration from diagnosis to the latest follow-up was 2.5 years (IQR: 1.6-4.6). Sensory (29.4 %), brainstem (23.5 %), and pyramidal (19.1 %) symptoms were most common. Interferon beta (32.4 %), dimethyl fumarate (27.9 %) and rituximab (26.5 %) were the most frequently used first-line DMT. Patients had a median ARR of 0.5 (IQR: 0.08-0.84), and EDSS score of 1.0 (IQR: 0.0-2.0) at the most recent follow-up. Delayed DMT initiation correlated with higher ARR (R = 0.38, p = 0.0016) and longer 25-ft walk duration (R = 0.34, p = 0.0077). In multivariate analysis, delayed DMT remained a significant predictor of higher ARR (p = 0.002) and longer 25-ft walk duration (p = 0.047). Delayed DMT initiation and use of low/moderate efficacy DMT predicted GAD enhancing lesions at the latest follow-up (p = 0.004 and 0.019 respectively).
    CONCLUSIONS: Delayed DMT initiation in POMS is linked to unfavorable outcomes, including higher ARR and longer 25-ft walk duration.
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  • 文章类型: Case Reports
    结核性多发性硬化症(MS)是非典型和罕见MS的一种亚型,在中枢神经系统中表现为肿瘤样病变。病变可能表现出质量效应,水肿,环增强。在放射学和临床上,它们可能被误认为是脑肿瘤或脑脓肿。在这里,我们描述了一个有启发性的55岁女性患者,她的右臂和腿偶尔出现麻木,头痛,思想混乱,视力模糊了2年.
    Tumefactive multiple sclerosis (MS) is a subtype of atypical and rare MS that presents with tumor-like lesions in the central nervous system. The lesions may demonstrate a mass effect, edema, with ring enhancement. They can be mistaken for brain tumors or brain abscesses radiologically and clinically. Here we describe an instructive case of a 55-year-old woman with tumefactive MS who presented with occasional numbness in her right arm and leg, headache, thought confusion, and blurred vision for 2 years.
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  • 文章类型: Journal Article
    目的:我们研究了L-肉碱(LC)对Cuprizone(Cup)脱髓鞘大鼠模型的影响及其可能的潜在机制。
    方法:将30只雄性SD大鼠随机分为3组:正常对照组;其中Cup以450mg/kg/天的剂量通过胃灌胃给药5周;和Cup+LC组,它接受了与杯子组相同剂量的杯子,除了大鼠另外用LC100mg/kg/天口服治疗5周。测量孤立的坐骨神经的神经传导(NCV);然后,分离坐骨神经进行H&E染色和电镜检查。髓鞘碱性蛋白(MBP)的表达,IL-1β,p53,iNOS,通过免疫组织化学在分离的神经中检测到和NF-kB。还进行了PCR测定以检测抗氧化基因Nrf2和HO-1的表达。此外,ELISA法检测IL-17水平。
    结果:与正常大鼠相比,Cup组的NCV显着降低(p<0.001),LC组显著改善(p<0.001)。EM和组织病理学检查显示坐骨神经纤维明显脱髓鞘和恶化,LC组有显著改善。IL-17的水平以及IL-1β的表达,p53,iNOS,NF-κB显著增加,坐骨神经中MBP的表达显着降低(p<0.01),LC处理显著改善了所研究的参数(p<0.01)。
    结论:本研究证明了LC在Cup诱导的脱髓鞘大鼠模型中的神经保护作用。这种作用可能是由于其抗炎和抗氧化作用。
    OBJECTIVE: We investigated the effect of L-carnitine (LC) on cuprizone (Cup) demyelinating rat model and its possible underlying mechanisms.
    METHODS: Thirty male Sprague-Dawley (SD) rats were randomly allocated to three groups: the normal control group; the Cup group, in which Cup was administrated at a dose of 450 mg/kg per day orally via gastric gavage for 5 weeks; and the Cup + LC group, which received the same dose of Cup as the Cup group, except that the rats were treated additionally with LC 100 mg/kg/day orally for 5 weeks. The nerve conduction (NCV) in isolated sciatic nerves was measured; then, the sciatic nerves were isolated for H&E staining and electron microscope examination. The expression of myelin basic protein (MBP), IL-1β, p53, iNOS, and NF-KB by immunohistochemistry was detected in the isolated nerves. A PCR assay was also performed to detect the expression of antioxidant genes Nrf2 and HO-1. In addition, the level of IL-17 was measured by ELISA.
    RESULTS: There was a significant reduction in NCV in the Cup group compared to normal rats (p < 0.001), which was significantly improved in the LC group (p < 0.001). EM and histopathological examination revealed significant demyelination and deterioration of the sciatic nerve fibers, with significant improvement in the LC group. The level of IL-17 as well as the expression of IL-1β, p53, iNOS, and NF-KB were significantly increased, with significant reduction expression of MBP in the sciatic nerves (p < 0.01), and LC treatment significantly improved the studied parameters (p < 0.01).
    CONCLUSIONS: The current study demonstrates a neuroprotective effect of LC in a Cup-induced demyelinating rat model. This effect might be due to its anti-inflammatory and antioxidant actions.
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  • 文章类型: Journal Article
    目的:为了研究香草酸(VA)对Cuprizone(Cup)脱髓鞘大鼠模型的作用以及这种作用背后的机制。
    方法:成年雄性SD大鼠30只,随机分为3组:对照组,Cuprizone,和VA组。Cuprizone以450mg/kg/天的剂量经胃灌胃给药5周。在孤立的坐骨神经中研究了神经传导速度(NCV),然后分离坐骨神经进行组织病理学检查,电子显微镜检查,免疫组织化学染色,生化和PCR检测。使用ELISA检测IL17的水平,而抗氧化基因Nrf2、HO-1在mRNA水平表达,髓鞘碱性蛋白(MBP)的表达,干扰素-γ因子(INF)-γ和肿瘤坏死因子(TNF)-α,和凋亡标志物(caspase-3)使用免疫组织化学在坐骨神经中进行测量。
    结果:与正常大鼠相比,Cup的NCV显着降低(p<0.001),VA组明显改善(p<0.001)。EM和组织病理学检查显示,VA组的坐骨神经纤维明显脱髓鞘和恶化,并有显着改善。IL17的水平以及INF-γ和caspase-3的表达显着增加,MBP的表达显着降低,坐骨神经中的Nrf2和HO-1(p<0.01),和VA处理显着改善了研究参数(p<0.01)。
    结论:本研究证明了VA对Cup诱导的脱髓鞘大鼠模型的神经保护作用。这种效应可能是通过抑制炎症来沉淀的,氧化应激,和凋亡。
    OBJECTIVE: To investigate the effect of vanillic acid (VA) on a Cuprizone (Cup) demyelinating rat model and the mechanisms behind such effect.
    METHODS: Thirty adult male Sprague Dawley (SD) rats were randomly divided into three groups: control, Cuprizone, and VA groups. Cuprizone was administrated at a dose of 450 mg/kg per day orally via gastric gavage for 5 weeks. The nerve conduction velocity (NCV) was studied in an isolated sciatic nerve, and then the sciatic nerve was isolated for histopathological examination, electron microscope examination, immunohistochemical staining, and biochemical and PCR assay. The level of IL17 was detected using ELISA, while the antioxidant genes Nrf2, HO-1 expression at the level of mRNA, expression of the myelin basic protein (MBP), interferon-gamma factor (INF)-γ and tumor necrosis factor (TNF)-α, and apoptotic marker (caspase-3) were measured using immunohistochemistry in the sciatic nerve.
    RESULTS: There was a significant reduction in NCV in Cup compared to normal rats (p < 0.001), which was markedly improved in the VA group (p < 0.001). EM and histopathological examination revealed significant demyelination and deterioration of the sciatic nerve fibers with significant improvement in the VA group. The level of IL17 as well as the expression of INF-γ and caspase-3 were significantly increased with a significant reduction in the expression of MBP, Nrf2, and HO-1 in the sciatic nerve (p < 0.01), and VA treatment significantly improved the studied parameters (p < 0.01).
    CONCLUSIONS: The current study demonstrated a neuroprotective effect for VA against the Cup-induced demyelinating rat model. This effect might be precipitated by the inhibition of inflammation, oxidative stress, and apoptosis.
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  • 文章类型: Journal Article
    背景:复发或复发性根瘤性脱髓鞘很少见,除了个别病例报告外,还没有研究过。
    目的:我们检查了临床病程,神经影像学,脑脊液(CSF),复发性肿瘤性脱髓鞘病变(TDL)患者的治疗和预后。
    方法:我们使用PubMed来识别复发性TDL的报告,并包括其他细节,未发表的患者。
    结果:我们确定了18例(11F,7米)。指数TDL发作的中位年龄为37岁(范围12-72),大多数为孤立性病变72%(13/18)。在25%(4/16)中检测到CSF限制性寡克隆带(OCB)。只有一个测试的人(n=13)对AQP4-IgG呈阳性。中度至显著的治疗反应(高剂量皮质类固醇,有或没有额外的血浆置换,IVIg或疾病改善疗法)在89%的治疗患者中很明显。中位随访36个月(范围6-144)时的EDSS中位数为2(范围1-10)。大多数人仍在门诊(EDSS<4in13/18),但有1名患者死亡。
    结论:复发性TDL患者的中位年龄与典型MS相似,但差异包括较低的女性:男性性别比例,较大的病变,和相对缺乏CSF限制的OCB。该组患者的结果各不相同,从最小残疾到死亡。
    BACKGROUND: Relapsing or recurrent tumefactive demyelination is rare and has not been studied beyond individual case reports.
    OBJECTIVE: We examined the clinical course, neuroimaging, cerebrospinal fluid (CSF), treatment and outcomes of patients with recurrent tumefactive demyelinating lesions (TDLs).
    METHODS: We used PubMed to identify reports of recurrent TDLs and included the details of an additional, unpublished patient.
    RESULTS: We identified 18 cases (11F, 7 M). The median age at onset of the index TDL was 37 years (range 12-72) and most were solitary lesions 72 % (13/18). CSF-restricted oligoclonal bands (OCBs) were detected in 25 % (4/16). Only one of those tested (n = 13) was positive for AQP4-IgG. A moderate-to-marked treatment response (high dose corticosteroid with or without additional plasmapheresis, IVIg or disease modifying therapies) was evident in 89 % of treated patients. Median EDSS at the median follow-up of 36 months (range 6-144) was 2 (range 1-10). Most remained ambulatory (EDSS < 4 in 13/18), but 1 patient died.
    CONCLUSIONS: The median age of patients with relapsing TDLs is similar to that of typical MS, but differences include a lower female:male sex ratio, larger lesions, and a comparative lack of CSF-restricted OCBs. Outcomes vary among this group of patients ranging from minimal disability through to death.
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  • 文章类型: Journal Article
    暂无摘要。
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  • 文章类型: Journal Article
    脱髓鞘疾病是一种神经系统疾病,其特征是神经系统中髓鞘的损伤。促进少突胶质细胞前体细胞(OPCs)的增殖和分化对于治疗至关重要。非选择性毒蕈碱受体(MR)拮抗剂已被证明可以改善啮齿动物模型中的髓鞘再生,尽管机制尚不清楚。在这项研究中,我们用不同浓度的索利那新(Sol)处理铜(CPZ)小鼠模型,选择性M3受体阻断剂,以确定促进髓鞘再生的最佳浓度。使用行为测试和Luxol坚固蓝(LFB)染色观察髓鞘再生的程度,而免疫荧光用于测量髓鞘相关蛋白的表达水平,包括髓鞘碱性蛋白(MBP)和血小板衍生生长因子受体α(PDGFRα)。采用蛋白质印迹分析来分析与Wnt/β-连环蛋白信号通路相关的分子的表达水平。结果表明,Sol处理显著促进CPZ诱导小鼠模型的髓磷脂再生和OPCs分化。此外,溶胶处理抑制Wnt/β-catenin信号通路并逆转CPZ对OPCs分化的影响。总之,溶胶可能通过抑制Wnt/β-catenin信号通路促进OPCs分化,使其成为中枢脱髓鞘疾病的潜在治疗选择。
    Demyelinating diseases are a type of neurological disorder characterized by the damage to the myelin sheath in the central nervous system. Promoting the proliferation and differentiation of oligodendrocyte precursor cells (OPCs) is crucial for treatment. Non-selective muscarinic receptor (MR) antagonists have been shown to improve remyelination in rodent models, although the mechanisms are still unclear. In this study, we treated cuprizone (CPZ)-induced demyelination mouse model with different concentrations of Solifenacin (Sol), a selective M3 receptor antagonist, to determine the optimal concentration for promoting remyelination. Behavioral tests and Luxol fast blue (LFB) staining were used to observe the extent of remyelination, while immunofluorescence was used to measure the expression levels of myelin-related proteins, including myelin basic protein (MBP) and platelet-derived growth factor receptor alpha (PDGFR-α). Western blot analysis was employed to analyze the expression levels of molecules associated with the Wnt/β-catenin signaling pathway. The results showed that Sol treatment significantly promoted myelin regeneration and OPCs differentiation in CPZ-induced demyelination mouse model. Additionally, Sol treatment inhibited the Wnt/β-catenin signaling pathway and reversed the effects of CPZ on OPCs differentiation. In conclusion, Sol may promote the differentiation of OPCs by inhibiting the Wnt/β-catenin signaling pathway, making it a potential therapeutic option for central nervous system demyelinating diseases.
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  • 文章类型: Meta-Analysis
    我们决定用荟萃分析进行第一次系统评价,以提供有关多发性硬化症职业危险因素的最高水平的最新证据。
    系统,在四个电子学术数据库中进行了全面的文献检索。我们纳入了任何招募工作年龄受试者的病例对照研究,并比较了MS病例与未暴露于职业危险因素的对照组的比例。主要结果是MS的发生。质量评估是用病例对照研究的关键评估清单进行的,开发,由乔安娜·布里格斯研究所验证。所有选择过程也由两名独立且先前受过训练的研究人员进行。
    总的来说,总样本包括19,004名MS患者和4,164,162名对照。农业工人(OR=1.44,95%CI1.13-1.83),离岸工人(OR=3.56,95%CI2.74-4.61),和美发师(OR=8.25,95%CI1.02-66.52)与更高的被诊断为MS的可能性相关。并行,暴露于油井有毒烟雾的工人(OR=16.80,95%CI8.33-33.90),低频磁场(OR=1.71,95%CI1.03-2.72),农药(OR=3.17,95%CI=2.53-3.99)也增加了患MS的可能性。
    我们的研究有可能影响更自信的公共政策。然而,我们强烈建议未来研究职业环境如何影响MS的发病率.
    该方案已在国际前瞻性系统评价登记册(PROSPERO-CRD42023443257)中注册。
    We decided to conduct the first systematic review with meta-analysis to provide the highest level of up-to-date evidence on the occupational risk factors for Multiple Sclerosis.
    A systematic, comprehensive literature search was performed in four electronic academic databases. We included any case-control study that enrolled working-age subjects and compared the proportion of MS cases with controls who were not exposed to an occupational risk factor. The primary outcome was the occurrence of MS. The quality assessment was performed with the Critical Appraisal Checklist for Case Control Studies, developed, and validated by the Joanna Briggs Institute. All the selection process was also carried out by two independent and previously trained researchers.
    Overall, the total sample included 19,004 people with MS and 4,164,162 controls. Agricultural workers (OR = 1.44, 95% CI 1.13-1.83), offshore workers (OR = 3.56, 95% CI 2.74-4.61), and hairdressers (OR = 8.25, 95% CI 1.02-66.52) were associated with a higher probability of being diagnosed with MS. In parallel, workers exposed to toxic fumes from oil wells (OR = 16.80, 95% CI 8.33-33.90), low-frequency magnetic fields (OR = 1.71, 95% CI 1.03-2.72), and pesticides (OR = 3.17, 95% CI = 2.53-3.99) also had an increased likelihood of having MS.
    Our study has the potential to influence more assertive public policies. Nevertheless, future studies on how the occupational setting may contribute to the incidence of MS are highly recommended.
    The protocol was registered in the international prospective register of systematic reviews (PROSPERO- CRD42023443257).
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