神经重复电刺激对重症肌无力眼肌型的诊断价值

目的：探讨神经重复电刺激检查在重症肌无力（MG）眼肌型患者的诊断价值。方法对46例临床拟诊的重症肌无力（MG）眼肌型患者进行神经重复电刺激检查,并对结果进行分析。结果共测试46例MG眼肌型患者,单上睑下垂者20例,双眼睑下垂者19例,复视者有3例,吞咽困难者2例,咀嚼无力2例。共对204条神经进行神经电生理检测：MG眼肌型患者在疲劳试验前,单独刺激眼轮匝肌、三角肌和小指展肌RNS的阳性率分别为41.30%（19/46）、15.21%（7/46）、6.52%（3/46）,3块肌肉综合统计低频刺激的阳性率为58.69%（27/46）,高频刺激的阳性率为5%（6/46）。疲劳试验后眼轮匝肌、三角肌和小指展肌RNS阳性率分别为47.82%（22/46）、21.74%（10/46）、6.52%（3/46）。疲劳试验前后可见低频刺激阳性率均远高于高频刺激,且高频刺激阳性者在低频刺激时全部为阳性。疲劳试验后三角肌的RNS阳性率增加;面肌、小指展肌的RNS阳性率无明显变化;3块肌肉综合统计低频刺激下RNS阳性率增高。结论 MG为神经-肌肉接头传递功能障碍的获得性免疫性疾病,神经重复电刺激检查对MG眼肌型的诊断、鉴别诊断及指导治疗有重要价值。     

重症肌无力的免疫修饰治疗

重症肌无力是一种主要由乙酰胆碱受体抗体介导累及神经-肌肉接头的自身免疫疾病.免疫修饰治疗可明显减少重症肌无力患者病死率并提升社会生活质量,但可用免疫抑制剂品种多样且均有剂量相关性的不良反应.目前国内外研究者对符合重症肌无力的免疫抑制剂选取、具体使用方法等问题尚无确切定论,因此有必要对重症肌无力常用免疫修饰治疗的临床应用进行综述,为临床医师在重症肌无力个体化免疫修饰治疗方面提供参考.     

Preferential production of IgG1, IL-4 and IL-10 in MuSK-immunized mice

Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness associated with acetylcholine receptor (AChR), muscle-specific receptor kinase (MuSK) or low-density lipoprotein receptor-related protein 4 (LRP4)-antibodies. MuSK-antibodies are predominantly of the non-complement fixing IgG4 isotype. The MuSK associated experimental autoimmune myasthenia gravis (EAMG) model was established in mice to investigate immunoglobulin (Ig) and cytokine responses related with MuSK immunity. C57BL/6 (B6) mice immunized with 30 μg of recombinant human MuSK in incomplete or complete Freund's adjuvant (CFA) showed significant EAMG susceptibility (> 80% incidence). Although mice immunized with 10 μg of MuSK had lower EAMG incidence (14.3%), serum MuSK-antibody levels were comparable to mice immunized with 30 μg MuSK. While MuSK immunization stimulated production of all antibody isotypes, non-complement fixing IgG1 was the dominant anti-MuSK Ig isotype in both sera and neuromuscular junctions. Moreover, MuSK immunized IgG1 knockout mice showed very low serum MuSK-antibody levels. Sera and MuSK-stimulated lymph node cell supernatants of MuSK immunized mice showed significantly higher levels of IL-4 and IL-10 (but not IFN-γ and IL-12), than those of CFA immunized mice. Our results suggest that through activation of Th2-type cells, anti-MuSK immunity promotes production of IL-4, which in turn activates anti-MuSK IgG1, the mouse analog of human IgG4. These findings might provide clues for the pathogenesis of other IgG4-related diseases as well as development of disease specific treatment methods (e.g. specific IgG4 inhibitors) for MuSK-related MG.     

重症肌无力的动物模型研究进展

重症肌无力（MG）的动物模型研究成为当前关注的焦点。不同的MG实验模型在一定程度上反映了MG的多样性,但由于其各自的局限性,尚不能在一种模型中模拟MG的所有特征。实验性自身免疫性重症肌无力（EAMG）模型涵盖了参与抗乙酰胆碱受体免疫反应的关键细胞机制,为理解MG的免疫学特征提供了基础。被动转移模型的特点是疾病诱导简单,在单次注射抗体后24 h内迅速出现虚弱症状。基因工程的优势在于更具有特异性,能够更准确地模拟MG的遗传基础,弥补了EAMG模型的不足。药物诱导模型具有建模迅速、不涉及复杂免疫激活和抗原诱导的特性,然而,其在模拟疾病复杂性方面存在一定局限。体外模型对患者血清的表型和功能反应进行匹配,该模型能够更直观地观察异种细胞在疾病发展中的作用,更贴近临床实际。该综述总结了各种实验模型的优缺点,帮助研究者选择适用于不同研究目的的模型。为推动对该疾病复杂机制的深入理解提供方向,并为新的治疗策略的制定提供科学依据。     

从“髓海不足”论治重症肌无力

重症肌无力是一种自身免疫性神经系统疑难病症,是世界公认的难治性疾病。近年来,重症肌无力的治疗新路径仍是当下研究的热点,中医药治疗更是获得越来越多的关注。重症肌无力归属中医学“痿证”的范畴,“髓海不足,经脉失养”是其重要病机,中医从“髓海不足”论治是从“本”出发,能够更加快速有效地治疗疾病,是中医治疗重症肌无力的重要方法。本文从重症肌无力发生发展与“髓海不足”的关联进行分析,分别从中医理论基础藏象理论、精气学说、经络学说以及现代医学研究4个角度进行探讨,为中医从“髓海不足”论治重症肌无力提供理论依据;并在此基础上,提出从“髓海不足”论治重症肌无力需重视阴阳并补,以促进“髓”的功能恢复,以及需重视顾护脾胃,为“髓”提供源源不断的营养的临床诊疗思路。     

Newly diagnosed multiple sclerosis in a patient with ocular myasthenia gravis: A case report

Rationale:Patients with myasthenia gravis may also have comorbid autoimmune diseases. Since both myasthenia gravis and neuromyelitis optica spectrum disease are mediated by antibodies, they are likely to occur together. However, since multiple sclerosis is an autoimmune disease that is not mediated by a specific antibody, it has fewer immune mechanisms in common with myasthenia gravis than neuromyelitis optica spectrum disease. We encountered a case of newly developed multiple sclerosis in a patient with myasthenia gravis.Patient concerns:A 46-year-old man was diagnosed with ocular myasthenia gravis 6 years ago and had been taking pyridostigmine to control his symptoms.Diagnosis:The patient developed right optic neuritis, and multiple sclerosis was suspected based on the brain magnetic resonance imaging findings. However, the required diagnostic criteria were not met.Interventions:Disease-modifying therapy was not initiated, and clinical progression of the disease was monitored.Outcomes:One year after the onset of optic neuritis, the patient developed myelitis and was diagnosed with multiple sclerosis, prompting treatment with disease-modifying therapy.Lessons:When optic neuritis occurs in patients with myasthenia gravis, careful evaluation is necessary while considering the possibility that it may be the first symptom of a demyelinating central nervous system disease. Therefore, it is important to conduct shorter-interval monitoring and symptom screening for patients with neurological autoimmune diseases, such as myasthenia gravis, even if multiple sclerosis is not initially suspected, to achieve early detection of multiple sclerosis.     

临床药师在儿童全身型重症肌无力中的药学实践

临床药师对我院首发为全身型重症肌无力的14例患儿进行分级药学监护、出院时用药教育、出院后药学随访等管理措施,考察患儿的疾病和用药认知、用药依从性、疾病改善水平以及药品不良反应情况。Ⅲa型和Ⅳb型、Ⅱb型、Ⅱa型患儿分别接受一、二、三级药学监护。随访基线时,随访后1、3、6个月,末次随访时,14例患儿定量重症肌无力评分逐渐降低,对疾病和用药相关知识的评分逐渐上升,用药依从性上升,各组之间差异有统计学意义（P <0.05）,未出现严重药物不良反应。临床药师参与到儿童全身型重症肌无力治疗管理中,可提高患儿的疾病和用药认知水平以及用药依从性。     

Treatment of myasthenia gravis with the method of tonifying spleen and replenishing qi in traditional Chinese medicine: A protocol for systematic review and meta-analysis

Background:Myasthenia gravis (MG) is an autoimmune disease that is associated with the production of autoantibodies. The symptoms of MG are mainly mediated by pathogenic antibodies directed against nicotinic acetylcholine receptors, resulting in a decrease in the number of acetylcholine receptors molecules on the postsynaptic membrane of the neuromuscular junction endplate, leading to clinical symptoms of muscle fatigue and weakness. At present, traditional Chinese medicine (TCM) treatment of MG has a better effect by tonifying spleen and replenishing qi. The purpose of this study was to systematically evaluate the efficacy and safety of TCM therapy for tonifying spleen and replenishing qi in the treatment of myasthenia gravis.Methods:We searched the following databases from their establishment until December 2021: PubMed, Cochrane Library, EMBASE, Web of Science, Springer, CNKI, Wanfang, China Biomedical Database, China Science and Technology Journal Database, Chinese Knowledge Infrastructure, China Clinical Trial Registry, and Baidu Scholars. The literature search language was limited to Chinese and English, and publication time and status were not limited. Randomized controlled trials (RCTs) were included. Two researchers independently searched and screened the articles, assessed their quality, and used the RevMan 5.4.1 software to perform a meta-analysis of the included literature.Results:This study compared the main outcome indicators: efficacy rate, recurrence rate, quality of life, and quantitative myasthenia gravis (QMG). Secondary outcome indicators were the clinical absolute score, TCM syndrome score, serum acetylcholine receptor antibody level, and electromyogram low-frequency repetitive nerve stimulation.Conclusion:This study aimed to evaluate whether the TCM method of tonifying spleen and replenishing qi is effective in the treatment of MG and to provide evidence-based data.Ethics and dissemination:The protocol of the systematic review did not require ethical approval because it did not involve human subjects. This article will be published in peer-reviewed journals and will be presented at conferences.