一例重症肌无力危象病人的心理疏导

重症肌无力是累及神经肌肉接头突触后膜上乙酰胆碱受体的自身免疫性疾病。临床特征为部分或全身横纹肌异常地容易疲劳。胸腺瘤合并重症肌无力治疗较为棘手,术后并发肌无力危象给治疗带来了更大的困难,我科于1999年8月收治一例重症肌无力病人,术后当日即发生肌无力危象,入ICU进行呼吸机辅助呼吸近一个月,对呼吸机产生依赖心理,现将临床对其进行心理疏导措施介绍如下。     

血气监测指导药物滴定治疗重症肌无力危象1例

重症肌无力 （Myasthenia Gravis,MG） 是一种以神经肌肉接头处突触后膜功能障碍为特征的自身免疫性疾病, 该病以肌肉疲劳和无力为特征,其主要抗原靶点为乙酰胆碱受体 （Acetylcholine Receptor,AChR）。当累及膈肌等呼吸肌引起呼吸衰竭需要有创或无创通气时称之为肌无力危象 （Myasthenic Crisis,MC）,通气不足引起CO₂大量潴留、PCO₂升高及颅内压升高,进而导致意识障碍。因此,及时监测动态血气并采取精确治疗显得尤为重要。滴定抗胆碱酯酶剂治疗的目的是为药物转化提供合适的剂量,处理好“剂末现象”,为危象患者呼吸功能好转后提供更好的脱机条件。本文报道1例因感染引起吞咽困难、呼吸困难及意识障碍的抗AChR抗体阳性的重症肌无力危象患者,经动态监测血气、呼吸机辅助通气、控制感染及滴定抗胆碱酯酶药物治疗后好转出院。     

重症肌无力危象40例临床分析

目的:探讨重症肌无力(MG)危象的诱发因素、延长气管插管的因素以及并发症、病死率。方法:回顾分析46例次肌无力危象病人的年龄、性别、诱发因素及治疗措施。结果:478例MG中发生肌无力危象40例,发生率为9.6%,全为肌无力危象,无一例胆碱能危象和反拗性危象。40例发生危象前Osserm anⅠ型3例,Ⅱ型9例,Ⅲ型12例,Ⅳ型16例,Ⅴ型0例。感染发热性疾病及加、减药量过快或突然停药为危象发生的主要诱因,分别占47.8%和17.4%。6例次(13%)应用了加重MG的抗生素。医源性因素亦为不容忽视的重要诱因。本组死亡6例,病死率15%。结论:发生危象的主要为Osserm anⅢ型和Ⅳ型。感染发热性疾病及加、减药量过快或突然停药为危象发生的主要诱因。适当调整胆碱酯酶抑制剂的用量,联合应用甲基泼尼松龙和丙种球蛋白冲击,注意控制感染等综合措施治疗,可使肌无力危象病死率明显降低。     

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.     

难治性重症肌无力的治疗管理

重症肌无力是一种影响突触后膜的自身免疫性疾病,病态疲劳性肌无力为主要特点.近年来较多研究显示多种免疫抑制剂和单克隆抗体对重症肌无力的治疗具有重要作用.进一步熟知难治性重症肌无力的治疗进展对于改善患者的临床症状具有深远意义.     

胸腺切除治疗重症肌无力近期疗效及危象发生的影响因素

目的 分析胸腺切除治疗重症肌无力(MG)近期疗效及危象发生的影响因素.方法 回顾性分析436例胸腺切除治疗重症肌无力患者,对年龄、性别、病程、临床分型、胸腺病理类型、胸腺瘤病理分期、胸腺瘤病理类型等因素进行统计分析.结果 Ⅰ型患者术后近期症状稳定的比例较高[62.63%(186/297)],而ⅡA型以上患者术后近期改善及恶化的比例均较高,其差异有统计学意义(均为P＜0.05);各性别、年龄、病程、病理类型、胸腺瘤分期、胸腺瘤病理类型亚组间近期疗效差异无统计学意义(均为P＞0.05).Logistic回归分析显示,有无胸腺瘤(回归系数0.251)及肌无力分型(回归系数1.300)两个因素与术后危象发生有关(均为P＜0.05);伴有胸腺瘤的患者、ⅡA型以上患者术后发生危象概率明显偏高.结论 临床分型在ⅡA型以上MG患者术后近期症状易出现波动;患者性别、年龄、病程、病理类型、胸腺瘤分期、胸腺瘤病理类型与近期疗效无关;伴有胸腺瘤的MG患者、ⅡA型以上患者是术后危象发生的高危人群,术前要充分估计风险,围术期注意预防.     

中西医结合治疗对重症肌无力患者外周血Treg、Tfh细胞的影响

目的 探索中西医结合治疗对重症肌无力患者外周血Treg、Tfh细胞的影响.方法 选取我院长期随访治疗的重症肌无力(MG)患者及根据年龄、性别匹配的健康对照,比较患者与健康对照组外周血Tfh、Treg细胞及Tfh/Treg比值,监测治疗前后重症肌无力患者外周血上述指标的变化.结果 健康对照组,眼肌型、全身型重症肌无力患者外周血Treg细胞以及重症肌无力患者治疗前后差异无统计学意义(P>0.05).治疗前重症肌无力患者Tfh及Tfh/Treg比值高于健康对照组(P<0.01),全身型重症肌无力外周血Tfh显著高于眼肌型(P<0.01),治疗后全身型重症肌无力患者外周血Tfh较治疗前下降.重症肌无力患者治疗前后Tfh/Treg差异无统计学意义(P>0.05).结论 重症肌无力患者外周血免疫功能特别是外周血Tfh存在异常,中西医结合综合治疗可改善这种免疫功能异常,达到治疗作用.     

胸腺瘤术后合并重症肌无力危象30例临床分析

胸腺切除是治疗重症肌无力（MG）的有效方法，有报道有效率可达80％，但胸腺瘤术后常并发MG危象，导致死亡。我们自1992年2月至2003年2月共手术治疗89例胸腺瘤合并MG病人，术后发生MG危象30例，均抢救成功，无围手术期死亡。现总结如下：     

重症肌无力的免疫学研究进展

重症肌无力是抗乙酰胆碱受体抗体介导的、细胞免疫依赖性、补体参与的神经肌肉接头处的自身免疫病，其发病本质就是针对乙酰胆碱受体的免疫应答异常。辅助性T细胞、细胞因子及胸腺在重症肌无力的发病机制中起重要作用，肌细胞亦主动地参与了重症肌无力的发病过程。重症肌无力的免疫启动目前多倾向于交叉反应学说。     

Lambert-Eaton肌无力综合征的电生理特征性改变

Lambert-Eaton肌无力综合征(Lambert-Eaton Myasthenic Syndrom,LEMS)是累及神经肌肉接头处突触前膜乙酰胆碱释放部位的自体免疫性疾病。又称重症肌无力综合症、类重症肌无力。临床上分为癌性LEMS(50％～87％)和非癌性LEMS(13％～50％)两类。在癌性LEMS中以小细胞肺癌最为多见(占68％～     

重症肌无力单核苷酸多态性的研究进展

重症肌无力（MG）是一种由神经-肌肉接头处传递功能障碍所引起的获得性自身免疫性疾病，其发病机制目前尚未完全明确。经相关研究表明，多因素多基因的积累共同导致了重症肌无力的发生，其中遗传因素占有重要作用。单核甘酸多态性（ SNP ）是人类基因组中最常见的多态性，在已经发现的多态性中有高达90％以上是以单核苷酸多态性的形式存在的。目前研究人员已经发现大量与重症肌无力密切相关的风险单核苷酸多态性，该文将对最近几年重症肌无力发病风险与单核苷酸多态性的相关性研究进行综述。     

Insights in the autoimmunity of myasthenia gravis

Myasthenia gravis is a prototype anti-receptor autoimmune disease. Antibodies against proteins at the neuromuscular junction cause a defect in the signal transmission from nerve terminal to the damaged postsynaptic membrane. This issue of Autoimmunity reviews the mechanisms that lead to the destruction of the neuromuscular junction and the role of the thymus in myasthenia gravis and its animal models. In addition, this issue explores recent advances in diagnosis and treatment of this disease.     

Interleukin-4 receptor alpha polymorphisms in autoimmune myasthenia gravis in a Caucasian population

Autoimmune myasthenia gravis is a T-cell-dependent, antibody-mediated, rare neuromuscular disorder. Interleukin-4, acting via interleukin-4 receptor alpha, plays a pivotal role in B-cell differentiation and antibody production and has been implicated to influence disease progression in experimental autoimmune myasthenia gravis. Polymorphisms of the interleukin-4 receptor alpha gene have been shown to be associated with various autoimmune diseases. We compared the distribution of three polymorphisms of the interleukin-4 receptor alpha gene (S503P, rs1805015, Q576R, rs1801275, I75V, rs1805010), all affecting interleukin-4 signaling, in two cohorts of myasthenia gravis patients with ethnically matched controls. Although the distribution of the S503P and Q576R polymorphisms did not differ significantly between the groups, the frequency of the GG rare homozygote genotype of the I75V polymorphism was significantly higher in patients with myasthenia gravis. Our data suggest that the reduced responsiveness to interleukin-4 because the I75V polymorphism may contribute to the pathogenesis of myasthenia gravis.     

重症肌无力患者AchR-Ab、Titin-Ab的检测及其临床意义

目的 对重症肌无力患者血清乙酰胆碱受体抗体(AchR-Ab)、连接素抗体(Titin-Ab)进行检测,探讨其临床意义,为临床提供诊断、治疗的依据.方法 选取本院2013年1月至2014年12月收治的重症肌无力患者80例.依据胸部CT检查结果将患者分为伴胸腺瘤(MGT)组与不伴胸腺瘤(NTMG)组.测定各组患者外周血AchR-Ab与Titin-Ab的含量并统计阳性例数,探讨其用于诊断重症肌无力的价值及意义.结果 MG组AchR-Ab与Titin-Ab阳性率明显高于HC组,MGT组AchR-Ab与Titin-Ab阳性率明显高于NTMG组,全身型(Ⅱ～Ⅳ型)AchR-Ab与Titin-Ab阳性率明显高于眼睑型(Ⅰ型)组,差异具有统计学意义(P＜0.05).结论 AChR抗体作为临床使用最广泛的重症肌无力患者检测指标具有一定价值,Titin抗体是应用于重症肌无力患者合并胸腺瘤时敏感而特异的血清学指标,在重症肌无力患者中开展血清Titin抗体的测定对于胸腺瘤的诊断及判断预后具有重要的临床指导意义.     

Basement membrane proteins and reticulin in a normal thymus and the thymus in myasthenia gravis

Summary The distribution of basement membrane (BM) proteins, laminin and type IV collagen were studied immunohistochemically in a series of 12 normal thymuses representing different age groups (0–52 years) and in 10 cases of myasthenia gravis (age 7–53 years). The staining pattern was compared with that of conventional reticulin staining. BM proteins were present at the capsule-parenchyma interface and scantily distributed in the medullary stroma, where they were closely associated with reticulin fibres. The extrathymic perivascular space was effectively vizualized by the staining of the BM's marginal to it. The fiber network present in this space stained with reticulin stain and, less continuously, in BM stainings. Lymph node like tissue with germinal centers was occasionally present in the perivascular spaces in normal thymuses and commonly in the myasthenia gravis cases, where the perivascular spaces were often dilated. The BM's of the perivascular space were mostly continuous in normal cases, but discontinuities were observed in cases of myasthenia gravis, especially in the spaces which were widely dilated. Immunohistochemical detection of BM proteins seems to be useful in the study of thymic structure, particularly in the demonstration of the characteristic changes of the perivascular space in myasthenia gravis. It is suggested that the reticulin fibres present in the medulla and in the perivascular space contain laminin and type IV collagen.     

补脾强力复方治疗重症肌无力患者的疗效及其对 血清细胞因子的影响

目的 探讨补脾强力复方治疗重症肌无力患者的临床疗效及血清细胞因子的影响。方法 选择2017年9月~2019年5月在我科门诊及住院治疗的重症肌无力Ⅰ型和Ⅱa型患者共60例,采用随机数字表法分为对照组28例和治疗组32例。对照组给予强的松联合溴吡斯的明治疗,治疗组在对照组基础上加用补脾强力复方治疗,疗程均为12周,采用重症肌无力临床相对评分法和临床绝对评分法评估患者临床疗效,用ELISA法检测两组患者外周血AchR-Ab、IFN-γ、TNF-α、IL-4、IL-17水平,观察补脾强力复方的临床疗效、细胞因子水平变化及不良反应发生情况。结果 治疗组愈显率为75.00%,与对照组的68.00%比较,差异无统计学意义（P＞0.05）;治疗组总有效率为91.00%,高于对照组的71.00%（P＜0.05）。治疗后两组AChR-Ab、IFN-γ、TNF-α、IL-4、IL-17水平均低于治疗前（P＜0.05）,治疗组AChR Ab、IFN-γ、IL-17水平降低优于对照组（P＜0.05）;两组IL-4、TNF-α变化比较,差异无统计学意义（P＞0.05）。两组治疗期间均未见腹泻、腹痛、恶心、皮疹等不良反应,差异无统计学意义（P＞0.05）。结论 补脾强力复方可在一定程度上提高重症肌无力的近期临床疗效,其机制与下调血清IFN-γ和IL-17 水平、降低血清AChR-Ab水平可能有关。     

Immunosuppressive therapies in myasthenia gravis

Immunosuppression is the mainstay of treatment for myasthenia gravis (MG). In this paper, we review the mechanisms of action and clinical application of corticosteroids and different classes of immunosuppressive drugs that are currently used in MG patients, and present the results of their use in more than 1000 patients with MG seen at our two centers. Immunosuppressive treatment was considered along with, or as an alternative to thymectomy in MG patients with disabling weakness, not adequately controlled with anticholinesterase drugs. Overall, 82% of our patients received immunosuppressants for at least 1 year, with frequencies varying according to disease severity, from 93–95% of those with thymoma or MuSK antibodies to 72% in ocular myasthenia. Prednisone was used in the great majority of patients, azathioprine was the first-choice immunosuppressant; mycophenolate mofetil and cyclosporine were used as second-choice agents. All clinical forms of MG benefited from immunosuppression: the rate of remission or minimal manifestations ranged from 85% in ocular myasthenia to 47% in thymoma-associated disease. Treatment was ultimately withdrawn in nearly 20% of anti-AChR positive early-onset patients, but in only 7% of thymoma cases. The risk of complications appears to depend on drug dosage, treatment duration, and patient characteristics, the highest rate of serious side effects (20%) having been found in late-onset MG and the lowest (4%) in early-onset disease. Although nonspecific, current immunosuppressive treatment is highly effective in most MG patients. Lack of randomized evidence, the need for prolonged administration, and unwanted effects are still relevant limitations to its use.     

全胸腔镜下胸腺切除术治疗无重症肌无力早期胸腺瘤30例

目的：探讨全胸腔镜下胸腺切除术治疗无重症肌无力早期胸腺瘤的临床价值。方法：回顾性分析30例经全胸腔镜下胸腺切除术治疗无重症肌无力早期胸腺瘤患者的临床资料,总结其手术方法、分期、病理学类型、后续治疗、并发症、随访结果等。结果：30例患者全部经右侧胸腔镜完成胸腺切除术,其中男性12例、女性18例,无中转开胸,无围手术期死亡和严重并发症;手术时间40—200min,平均（91．7±38．1）min,出血量30～300ml,平均（106±75）ml;术后住院时间5—7d,平均（5．1±0．8）d。术后临床分期,I期17例（56．7％）、II期13例（43．3％）。病理学类型,A型14例、AB型10例、B1型5例、B2型1例。Ⅱ期患者术后均接受辅助放疗。患者全部随访,随访时间6—72个月,中位随访时间44个月。随访期内无一例复发或死亡,总生存率（OS）为（70．2±1．7）个月（95％CI：66．8—73．6）。结论：全胸腔镜下胸腺切除术治疗无重症肌无力早期胸腺瘤安全、有效,而且更加微创,值得临床推广应用。