重症肌无力指南(2015)

• 抗-MuSK 抗体阳性率，欧美国家患者较亚 洲国家患者高。
2015中国重症肌无力诊断和治疗指
肌无力。 • 部分患者短期内出现全身肌肉收缩无力,甚至发生肌无力
危象。
2015中国重症肌无力诊断和治疗指
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受累肌群
• 眼外肌：对称或非对称性上睑下垂和/或双眼复视，是MG 最常见的首 发症状，见于80%以上的MG 患者；还可出现交替性上睑下垂、双侧 上睑下垂、眼球活动障碍等。瞳孔大小正常,对光反应正常。
助呼吸。
2015中国重症肌无力诊断和治疗指
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四、临床分类（改良Osserman 分型）
• Ⅰ型：眼肌型，病变仅局限于眼外肌，两年之内其他肌群 不受累。
• Ⅱ型：全身型，有一组以上肌群受累。 • ⅡA 型：轻度全身型，四肢肌群轻度受累，伴或不伴眼外肌 • 受累，通常无咀嚼、吞咽和构音障碍，生活能自理。 • ⅡB 型：中度全身型，四肢肌群中度受累，伴或不伴眼外肌 • 受累，通常有咀嚼、吞咽和构音障碍，生活自理困难。 • Ⅲ型：重度激进型，起病急、进展快。发病数周或数月内
累及咽喉肌；半年内累及呼吸肌，伴或不伴眼外肌受累, 生活不能自理。
• Ⅳ型：迟发重度型，隐袭起病，缓慢进展。两年内逐渐进 展，由Ⅰ、ⅡA、ⅡB 型进展，累及呼吸肌。
• Ⅴ型：肌萎缩型，起病半年内可出现骨骼肌萎缩、无力。
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五、实验室检查
1、甲基硫酸新斯的明试验：
• 成人肌内注射1.0-1.5mg，如有过量反应，可予以肌肉注 射阿托品0.5mg，以消除其M 胆碱样不良反应；儿童可按 0.02-0.03mg/kg，最大用药剂量不超过1.0mg。
• 服用胆碱酯酶抑制剂的MG患者需停药12-18 小时 后做此项检查，但需要充分考虑病情。

A Medical Guide for Patients with Myasthenia Gravis重症肌无力患者指南重症肌无力协会尽最大努力确保其手册中的信息在出版时是完整的和最新的，但是根据英国法律，协会不会对其内容的不准确性或其它可能发生的问题负法律责任每一个重症肌无力病人的情况都不相同，这本手册只能提供我们目前通常的见解，有可能不是唯一的见解。

因此其它人有可能有不同意见重症肌无力及其相关疾病的信息重症肌无力协会（MGA）现在已经更新了关于不同类型的肌无力：重症肌无力，Lambert-Eaton 肌无力综合征和遗传性（先天性）肌无力手册上的资料。

许多患者想充分了解他们所患疾病的本质，这些知识不仅对患者自己有帮助，而且对他们的家人同样有用。

它同样也能使患者容易理解医生是如何在尽力帮助他们。

尽管关于肌无力的相关信息可以在网络上找到，但它并不总是以一个门外汉容易理解的形式叙述的。

我们中有许多同仁为这本新版手册的问世作出了贡献，我们希望这些手册里的信息能容易理解。

但我相信这里仍有改进的空间，因此我们非常感激您的反馈，这将有助于我们继续编写下一版本。

如果您未曾听说过MGA, 对以下信息您也许会有兴趣了解：该协会成立于1968年，1976年独立，1995年开始与一间公司合作。

协会的目标就是为肌无力患者及家人提供关心和支持，促进关于疾病病因和发展更好的治疗手段的研究。

协会希望能与患者/社区成员建立紧密联系，同样希望与医疗人员，研究者建立密切联系。

我们通过当地的分支机构、分部、区域性或国际性的会议（通常有一个专家主讲），或MGA 新闻以及我们的信息手册来建立这些联系。

我们目前的会员接近1，500人。

我们希望您能从中找到有用的信息，请让MGA了解您的意见。

John Newsom-Davis 医学博士主席目录关于这本指南 (5)1 重症肌无力简介 (6)什么是重症肌无力？ (8)患上重症肌无力意味着什么? (6)症状是什么样的? (8)什么会导致重症肌无力恶化？ (9)谁会患重症肌无力？ (9)2 哪里出了问题和为什么会出现问题 (11)正常肌肉的“点火系统”以及它是如何出现问题的 (11)免疫系统以及其如何出现问题的 (13)3 重症肌无力是如何诊断的 (15)4 重症肌无力是如何治疗的 (16)1 一些普通的方法 (16)2 溴吡啶斯的明 (17)3血浆交换和IvIg (18)4胸腺切除术 (19)5长期免疫抑制剂 (19)5麻醉剂与重症肌无力 (22)A 肌肉松弛剂 (23)B 溴化吡啶斯的明 (24)C 激素 (24)D 与麻醉师交谈 (24)E胸腺切除术 (25)6家庭与妇女问题 (25)7前景如何？ (26)8历史 (27)9其他类型的肌无力 (28)10牙科与重症肌无力 (31)11眼肌型重症肌无力 (32)附录1对恐慌不安初学者的简单科学知识 (36)附录2术语表 (39)关于这本指南由于每一位重症肌无力患者的经历各不相同，这本指南只能提供一般性的见解。

重症肌无力诊疗指南重症肌无力（Myasthenia·Gravis,MG）是一种表现为神经肌肉接头传递障碍的获得性自身免疫性疾病，临床特征为一部分或全身横纹肌软弱和异常疲劳；通常在活动后加剧，休息后减轻。

患病率约为5/10万，女性多于男性。

各年龄组均可发病。

自青年期至40岁间发病者，以女性为多；中年以后发病者，则以男性为多，本组中胸腺瘤较多见。

【临床表现】1、眼外肌是最常受累的肌肉，可表现为眼睑下垂、斜视和复视，双侧常不对称。

其次为颅神经支配的其他肌群，颈肌，肩胛带以及髋部的屈肌。

受累肌肉呈现为易疲劳和波动性。

连续收缩后发生无力，经短期休息后好转。

早晨症状较轻而傍晚时加重。

整个病程可有波动，病程早期可有自发缓解和复发。

2、特殊类型短暂新生儿重症肌无力为女性患者所生的婴儿暂时有经胎盘输入的母体AchR抗体。

大约有10%呈现不同程度的临床症状。

患婴全身软弱，哭声轻微，吸吮无力，上脸下垂，严重者有呼吸困难，经救治后可在数日内或数周内痊愈。

3、先天性肌无力出生后或儿童期出现肌无力，持续存在眼外肌麻痹。

母亲虽无重症肌无力，但家族中或同胞兄弟姐妹有肌无力病史。

4、重症肌无力患者除上述的临床表现外，神经系统检查体征主要是疲劳试验（＋）。

腱反射正常或活跃。

Osserman根据受累部位和严重程度，可分为5型。

1型单纯眼肌型，始终仅累及眼肌。

2型轻度全身肌无力型。

不伴明显延髓肌麻痹者为lla型，伴有明显延髓肌麻痹者为llb型。

3型急性进展型。

常在首次症状出现后数月之内发展至包括延髓肌、肢带肌、躯干肌和呼吸肌的严重无力。

4型为晚发型全身肌无力。

由l,lla,llb发展而来，常在首发症状出现后数年或数十年后出现全身无力。

5型肌无力伴肌萎缩者。

以上各型患者，如果急骤发生呼吸肌严重无力，不能维持换气功能时，称为危象。

可分为三种（1）肌无力危象为疾病发展所致。

多见于暴发或严重的全身型。

静脉注射腾喜龙2～10mg或肌肉注射硫酸新斯的明1.5mg可见暂时好转。

重症肌无力健康教育指南【教育评估】1、身体状况了解病人有无饮水呛咳、肌肉萎缩、吞咽困难及呼吸困难；了解病人及家属的心理情况，有无焦虑和恐惧；了解病人既往有无住院的经历、家庭经济情况如何。

2、学习要求了解病人、家属的学习能力及对疾病的认识程度；是否了解疾病的原因、诱因、发病特点及发生危象的严重后果；是否清楚主要治疗药物的作用及用药的注意事项，是否掌握病情观察要点、进食技巧及安全防护措施。

【与教育有关的护理问题】1、低效性呼吸形态：与呼吸肌麻痹致呼吸障碍有关2、有误吸的危险：与呼吸肌麻痹、咳嗽反射和呕吐反射减弱、吞咽障碍有关3、不能维持自主呼吸：与呼吸肌疲劳有关4、营养失调：低于机体需要量，与脑神经受损引起的吞咽／咀嚼困难有关5、语言沟通障碍：与言语肌肉的运动失调引起发音不良有关6、焦虑/恐惧：与知识缺乏，担心疾病的预后有关7、活动无耐力：与神经肌肉疾病引起的肌无力、全身疲乏，用力后不适或呼吸困难有关。

8、功能障碍性撤离呼吸机反应：与病人缺乏有关撤机过程的知识、信心不足有关。

【教育目标】教育对象能够：1、简述重症肌无力的表现及治疗、护理的方法。

2、主动配合治疗、护理。

3、演示自我护理技能。

4、复述出院后注意事项。

【教育内容】1、疾病简介：重症肌无力是一种神经肌肉传递障碍的得性自身免疫性疾病。

本病多数病人伴有胸腺增生或胸腺肿瘤，感染、精神创伤、过度劳累、妊娠分娩可诱发或加重病情，临床特征为部分或全身骨骼肌易于疲劳，通常在活动后加重，休息后减轻，晨轻幕重，最常见的首发症状为眼外肌不同程度乏力，其他如咀嚼肌、咽喉舌肌，面肌，四肢肌肉也可受累，分别出现上睑下垂、复视、吞咽困难、发音困难、四肢无力等，如侵犯呼吸肌则出现呼吸困难，称为重症肌无力危象，是致死的主要原因，心肌也可受累，可引起突然死亡。

2、心理指导：本疾病起病隐袭，症状明显，影响日常活动，严重时被迫卧床，因而病人易产生恐惧、焦虑、紧张等悄绪、护士应关心体贴病人、协助生活护理、多与其交谈，向病人和家属讲述本病的起因、过程，鼓励其保持乐观情绪，树立战胜疾病的信心，积极配合治疗和护理。

套式感觉减退，腱反射减低或消失。肌电图示运动或感觉神经传导速度减慢、波幅降低和传导阻滞。脑脊液有蛋白 -细胞分离现象，周围神经活检有助于诊断。
• ③Lambert-Eaton 综合征：免疫介导的累及神经肌肉接头突触前膜电压依赖性钙通道的疾病，表现 为肢体近端无力、易疲劳，短暂用力后肌力增强，持续收缩后病态疲劳伴有自主神经症状(口干、体 位性低血压、胃肠道运动迟缓、瞳孔扩大等)。肌电图示低频重复电刺激可见波幅递减，高频重复电
第十六页，共40页。
(2)全身型MG 的鉴别诊断
• ①Guillain-Barré综合征：免疫介导的急性炎性周围神经病，表现为弛缓性肢体肌无力，腱反射减低或消失。 肌电图示运动神经传导潜伏期延长、传导速度减慢、阻滞、异常波形离散等。脑脊液有蛋白-细胞分离现象。
• ②慢性炎性脱髓鞘性多发性神经病(CIDP)：免疫介导的慢性感觉运动周围神经病，表现为弛缓性肢体肌无力，
体介导。
第一页，共40页。
二、流行病学资料
年平均发病率约为8.0-20.0/10 万人。MG 在各个年龄阶段均可发 病。在40 岁之前,女性发病率高于男性;在40-50 岁之间男女发病
率相当;在50 岁之后,男性发病率略高于女性。
第二页，共40页。
三、临床表现
• 骨骼肌无力表现为波动性和易疲劳性,晨轻暮重,活动后加重,休息 和应用胆碱酯酶抑制剂后症状明显缓解、减轻。
第十五页，共40页。
2、鉴别诊断
(1)眼肌型MG 的鉴别诊断 • ①Miller-Fisher 综合征：属于Guillain-Barré综合征变异型，表现为急性眼外肌麻痹；
共济失调和腱反射消失；肌电图示神经传导速度减慢；脑脊液有蛋白-细胞分离现 象，在部分病人可检测到GQ1b 抗体。 • ②慢性进行性眼外肌麻痹(CPEO)：属于线粒体脑肌病，表现为双侧进展性无波动性眼

重症肌无力疲劳试验标准
重症肌无力（Myasthenia gravis，MG）疲劳试验是一种帮助诊断和评估MG疾病严重程度的常用方法。

下面是一些常见的重症肌无力疲劳试验标准：
1. 末梢肌疲劳试验（Peripheral Muscle Fatigability Test）：通过检查患者的末梢肌肌力变化来评估肌无力。

这可以通过要求患者保持重复肌肉运动（如握力测试）或持续进行特定动作（如闭眼眼球运动）来完成。

在MG患者中，肌肉疲劳的程度更快、更显著。

2. 简单疲劳试验（Simple Fatigability Test）：这个试验要求患者保持特定的肌肉活动一段时间，例如伸直手臂或举起双腿。

如果在持续活动后肌肉力量明显下降，则可能是MG症状。

3. 跳跃疲劳试验（Tensilon Test）：这是一项常用的诊断肌无力的试验。

在试验中，将琼脂球碱（Tensilon）注射患者体内后观察症状变化。

如果肌无力症状显著改善，则可能是MG。

4. 静脉疲劳试验（Intravenous Fatigability Test）：在这个试验中，患者经历一系列静脉注射及活动，以检测肌肉疲劳及其恢复情况。

需要注意的是，以上试验仅为常见的评估MG疲劳程度的方法之一，具体的试验方法和标准可能会根据个体情况和医生的判断而略有不同。

因此，在进行任何疲劳试验之前，请务必咨询医生以获得准确的诊断。

中国重症肌无力诊断和治疗指南一、本文概述《中国重症肌无力诊断和治疗指南》是一份权威的医学指南，旨在为医生和医疗工作者提供关于重症肌无力（Myasthenia Gravis, MG）的标准化诊断和治疗建议。

重症肌无力是一种由自身免疫系统异常引起的神经-肌肉接头传递障碍性疾病，临床表现为部分或全身骨骼肌无力和易疲劳。

本指南的编写目的是确保患者能够得到及时、准确和个性化的医疗服务，改善其生活质量，降低疾病对社会和家庭的影响。

本指南涵盖了重症肌无力的流行病学、发病机制、临床表现、诊断方法、治疗策略以及疾病管理等方面的内容。

通过全面系统地介绍重症肌无力的最新研究进展和临床实践经验，本指南旨在为医生提供科学、规范、实用的治疗建议，以促进重症肌无力患者的康复。

本指南也为政策制定者、医学教育工作者和科研人员提供了有价值的参考信息，有助于推动我国重症肌无力诊疗水平的提高。

本指南的制定遵循了科学、规范、实用的原则，充分借鉴了国内外相关指南和研究成果，结合我国实际情况，形成了具有中国特色的重症肌无力诊断和治疗方案。

我们希望本指南能够为广大医生和医疗工作者提供有益的帮助，共同推动我国重症肌无力诊疗事业的发展。

二、重症肌无力的病因与病理生理机制重症肌无力（Myasthenia Gravis，MG）是一种慢性自身免疫性疾病，主要表现为神经-肌肉接头的传递功能障碍。

其病因复杂，涉及遗传、免疫、环境等多因素。

遗传因素在MG的发病中起着重要作用，许多研究已经证实，MG与主要组织相容性复合体（MHC）基因、乙酰胆碱受体（AChR）基因、补体基因、T细胞受体基因、免疫球蛋白基因以及细胞因子基因等相关。

在病理生理机制方面，MG主要是由于患者体内产生了针对乙酰胆碱受体（AChR）的自身抗体，导致神经-肌肉接头的突触后膜乙酰胆碱受体数量减少或功能受损，进而影响了神经冲动的传递，使骨骼肌发生易疲劳现象。

MG患者体内还可能存在针对肌肉特异性激酶（MuSK）和低密度脂蛋白受体相关蛋白4（LRP4）的自身抗体，这些抗体同样可以影响神经-肌肉接头的功能。

一文搞定常见重症肌无力严重程度量表肌无力肌肉量表（MMS）该量表由Gajdos等人研制，于1997年正式发表于神经病学年鉴杂志[4]。

需要注意的是，与其它量表相比，该量表无呼吸肌相关评估内容。

条目数：9个总分：0～100分病情评估：得分越高提示病情越轻重症肌无力绝对和相对评分法（ARS-MG）该量表为我国许贤豪教授设计，于1997年发表[5]，现被用于《重症肌无力诊断和治疗中国专家共识》2012版，以及《中国重症肌无力诊断和治疗指南》2015版。

量表分为绝对评分和相对评分两部分，其中相对评分为通过公式计算得出。

条目数：8个总分：0～60分病情评估：得分越高提示病情越重量表简评目前已有多种工具用于评价MG的严重程度，根据高翔等人的研究[6]，上述4种严重程度量表信度和效度良好，均能可靠有效地评价MG的严重程度。

不同的量表特点和优势也有所差异，ARS-MG为我国自主设计，更适用于我国患者群体，但国外的量表同样有值得借鉴之处，临床上可根据评价内容、量表详略程度及使用目的做出选择。

在MG的量表研制方面，国内仍然有待进一步研究，期待未来能够诞生出更加适合于中国国情的量表[7]。

相关共识及指南下载：《重症肌无力诊断和治疗中国专家共识》2012版《中国重症肌无力诊断和治疗指南》2015版参考文献：[1] Penn A S, Sanders D B, Jaretzki A, et al. Myasthenia gravis: recommendations for clinical research standards[J]. Annals of Thoracic Surgery, 2000, 55(1):16-23.[2] 马铮, 蒋耀光, 王如文,等. 重症肌无力协会临床分型及定量评分的应用体会[J]. 中华胸心血管外科杂志, 2004, 20(2):89-92.[3] Burns T M, Conaway M, Sanders D B. The MG Composite: A valid and reliable outcome measure for myasthenia gravis.[J]. Neurology, 2010, 74(18):1434-1440.[4] Gajdos D P, Sylvie Chevret MD PhD, Bernard Clair M D, et al. Clinical trial of plasma exchange and high-dose intravenous immunoglobulin in myasthenia gravis[J]. Annals of Neurology, 1997, 41(6):789-96.[5] 王秀云, 许贤豪. 重症肌无力病人的临床绝对评分法和相对评分法[J]. 中华神经科杂志,1997(2):87-90.[6] 高翔, 张栩, 杨欢,等. 重症肌无力严重程度量表的评价[J].中华神经科杂志, 2016,49(5):375-381.[7] 罗迪, 刘凤斌, 侯政昆. 国内外重症肌无力临床结局评价常用量表介绍与评价[J]. 中国神经精神疾病杂志, 2013, 39(4):249-253.。

重症肌无力管理国际共识指南2020更新版11月3日，神经病学杂志发布了《重症肌无力管理国际共识指南（2020更新版）》，该共识指南基于文献中的最新证据，对2016年《重症肌无力管理国际共识指南》的内容进行了更新。

旨在指导世界各地临床医生的重症肌无力管理策略。

对指南中的要点进行摘译，供大家学习。

2016年《重症肌无力管理国际共识指南》是首个的重症肌无力国际共识指南，发布之前医脉通也对其中的指南要点进行总结。

制定背景2013年10月，美国Myasthenia Gravis基金会任命了一个工作组来制定重症肌无力（MG）的治疗指南，并召集了一个由15名国际专家组成的小组。

RAND / UCLA适当性方法用于制定涉及七个治疗主题的共识性建议。

2019年2月，国际专家小组重新召集，并增加了一名南美代表成员。

该小组对所有先前的建议重新进行了审核，并根据近期文献对需要纳入或更新的主题制定了新的共识建议。

多达三回合的匿名电子邮件投票用于达成共识，并根据专家小组的意见对建议进行了修改。

指南更新的部分包括胸腺切除术；针对利妥昔单抗、依库丽单抗和甲氨蝶呤的使用以及眼型MG的早期免疫抑制和免疫检查点抑制剂治疗相关的MG提出了新的建议。

在本指南共识中，经过三轮投票后未能达成共识的建议被删除。

专家小组以9分制对每项建议进行评分（1-3：不适当，4-6：不确定，7-9：适当），以中位数和范围表示。

共识指南中的主要内容➤胸腺切除术推荐意见： 1a.对于年龄在18至50岁之间，非胸腺性，AChR-Ab+全身性MG患者，应在疾病早期考虑进行胸腺切除术，以改善临床结局并最大程度地降低免疫治疗的需求或住院率（中位数9，范围2-9）。

1b.如果AChR-Ab +全身性MG患者对最初的免疫疗法没有反应或该疗法产生无法忍受的副作用，则应强烈考虑进行胸腺切除术（中位数9，范围5-9）。

2. MG胸腺切除术是择期手术，应在患者稳定且安全（不会因术后疼痛和机械因素限制呼吸功能）的情况下进行（中位数9，范围9）。

3.相关血清抗体的检测:
(1) 骨骼肌乙酰胆碱受体(AChR)抗体: 为诊断MG 的特异性抗体。约50%-60%的单纯 眼肌型MG 患者血中可检测到AChR 抗体；约 85%-90%的全身型MG 患者血中可检测到AChR 抗体。

结合肌无力病史，如抗体检测结果阳性则可以 确立MG 诊断。如检测结果为阴性，不能排除 MG 诊断。
二、流行病学资料
年平均发病率约为8.0-20.0/10 万人。MG 在各个年龄阶段均可 发病。在40 岁之前,女性发病率高于男性;在40-50 岁之间男女 发病率相当;在50 岁之后,男性发病率略高于女性。
三、临床表现 骨骼肌无力表现为波动性和易疲劳性,晨轻暮重,活动后加

重,休息和应用胆碱酯酶抑制剂后症状明显缓解、减轻。 全身骨骼肌均可受累。 颅神经支配的肌肉较脊神经支配的肌肉更易受累。 发病早期可单独出现眼外肌、咽喉肌或肢体肌肉无力。 经常从一组肌群无力开始,逐渐累及到其他肌群,直到全身 肌无力。 部分患者短期内出现全身肌肉收缩无力,甚至发生肌无力危 象。
五、实验室检查
1、甲基硫酸新斯的明试验：
成人肌内注射1.0-1.5mg，如有过量反应，可予以肌肉注射
阿托品0.5mg，以消除其M 胆碱样不良反应；儿童可按 0.02-0.03mg/kg，最大用药剂量不超过1.0mg。 注射前可参照MG 临床绝对评分标准。选取肌无力症状最 明显的肌群，记录一次肌力，注射后每10 分钟记录一次， 持续记录60 分钟。以改善最显著时的单项绝对分数，依照 公式计算相对评分作为试验结果判定值。相对评分=(试验 前该项记录评分-注射后每次记录评分) /试验前该项记录评 分×100%，作为试验结果判定值。其中≦25%为阴性， >25%-<60%为可疑阳性，≥60%为阳性 。 如检测结果为阴性，不能排除MG的诊断。

重症肌无力诊疗指南
重症肌无力主要是一种自身的免疫疾病，主要就是说自身产生了针对自己本身的乙酰胆碱受体的抗体，导致了神经递质间的传递障碍，患者因为这种发病的病型不同，可以临床表现是不一样的。

它可以有这种单纯的眼肌型患者，主要表现为双侧眼睑上抬费力，眼球的运动障碍，会出现复视的症状。

也有些患者是轻度的全身型，就是周身的乏力不适，拿东西拿不起，走路费力这些情况。

也有些患者会比较重，出现重症的全身型，患者可以出现行走障碍，然后会出现吞咽困难，饮水呛咳，构音障碍情况。

我们在治疗方面，就需要针对的治疗，可以用激素，用溴吡斯的明，以及一些免疫性的药物治疗，在重症肌无力的指南上面，就是有一些急性期的患者，还是推荐给他用人免疫丙种球蛋白的治疗，假如以上这些方法治疗效果都不好，患者还合并有胸腺瘤的话，我们指南上面推荐进行胸腺瘤的切除，还可以进行血液置换，血浆置换这些治疗，所以说，我们对于重症肌无力的治疗，还是要依据指南规范来进行诊治。

重症肌无力治疗指南
一、概述
患有重症肌无力这种疾病的患者由于自身身体的肌无力症状，会出现吞咽困难等不能维持基本生活的生命特征。

所以长期患有这种疾病对于患者的生活，工作甚至身体健康影响是非常大的。

所以重症肌无力疾病的一些治疗方法是非常重要的。

那么患了这种疾病应该如何正确的进行治疗呢？下面就一起来了解一下这方面的知识，分享某同事的一些经验吧！
二、步骤/方法：
1、不是特别严重的患者一般以药物治疗为主。

药物治疗的方面不论是西医还是中医都是有一定疗效的。

主要以缓解患者的肌肉乏力状态为主要治疗原则。

用药上面要严格遵从医师嘱咐。

有任何不良反应要及时跟医生汇报。

2、根据患者免疫功能的情况有部分患者也许会采用到免疫抑制剂得治疗。

部分患者利用这种方法疗程比较长。

如果临床上面有治疗条件的话也可以采取血液疗法。

但是这种治疗方法容易引起一些变态反应性的脑炎。

治疗效果并不是特别好所以一般没有被广泛采用。

有一定的副作用。

3、患有重症肌无力的患者一般还会伴有一些其他疾病，比如说胸腺瘤或者是甲状腺功能亢进等，有这些并发症的患者应该要在疾病治疗的同时也积极的治愈这种并发症。

有一些患者可能需要进行手术
治疗。

三、注意事项：
要注意重症肌无力如果治疗不及时的话，不仅会加重病情还会引发一系列更为严重的并发症。

比如说出现肌无力性危象，胆碱能性危象等表现病症。

患者咳嗽不停呼吸窘迫，还会导致腹胀腹泻的现象。

无力 • 部分患者短期内出现全身肌肉收缩无力甚至发生肌无力危
象
受累肌群
• 眼外肌：对称或非对称性上睑下垂和/或双眼复视是MG 最常见的首发 症状见于80%以上的MG 患者；还可出现交替性上睑下垂、双侧上睑 下垂、眼球活动障碍等瞳孔大小正常对光反应正常
• 面肌：眼睑闭合不全、鼓腮漏气、鼻唇沟变浅、苦笑或呈肌病面容 • 咀嚼肌：咀嚼困难 • 咽喉肌：吞咽困难、饮水呛咳、构音障碍、鼻音及声音嘶哑等 • 颈肌：以屈肌为著出现头颈活动障碍、抬头困难或不能 • 肢体各组肌群：肌无力症状以近端为著 • 呼吸肌：呼吸困难、无力部分病人可出现肌无力危象需行人工辅助呼
• 疗效：可以使70%-80%的MG 患者症状得到显著改善
• 副作用：约40%-50%的MG 患者肌无力症状在4-10 天内一过性加重并有可能促发肌无力危 象；同时应注意类固醇肌病补充钙剂和双磷酸盐类药物预防骨质疏松使用抗酸类药物预防 胃肠道并发症长期服用糖皮质激素可引起食量增加、体重增加、向心性肥胖、血压升高、 血糖升高、白内障、青光眼、内分泌功能紊乱、精神障碍、骨质疏松、股骨头坏死、消化 道症状等应引起高度重视
• ③Lambert-Eaton 综合征：免疫介导的累及神经肌肉接头突触前膜电压依赖性钙通道的疾病 表现为肢体近端无力、易疲劳短暂用力后肌力增强持续收缩后病态疲劳伴有自主神经症状口 干、体位性低血压、胃肠道运动迟缓、瞳孔扩大等肌电图示低频重复电刺激可见波幅递减高 频重复电刺激可见波幅明显递增多继发于小细胞肺癌也可并发于其它恶性肿瘤
2、鉴别诊断
1眼肌型MG 的鉴别诊断 • ①Miller-Fisher 综合征：属于Guillain-Barré综合征变异型表现为急性眼外肌
麻痹；共济失调和腱反射消失；肌电图示神经传导速度减慢；脑脊液有蛋白细胞分离现象在部分病人可检测到GQ1b 抗体 • ②慢性进行性眼外肌麻痹CPEO：属于线粒体脑肌病表现为双侧进展性无波 动性眼睑下垂、眼外肌麻痹可伴近端肢体无力肌电图示肌源性损害少数患者 可伴有周围神经传导速度减慢血乳酸轻度增高肌肉活检和基因检测有助于诊 断 • ③眼咽型肌营养不良OPMD：属于进行性肌营养不良症表现为无波动性的眼 睑下垂斜视明显但无复视肌电图示肌源性损害血清肌酶轻度增高肌肉活检和 基因检测有助于诊断 • ④眶内占位病变：眶内肿瘤、脓肿或炎性假瘤等所致表现为眼外肌麻痹并伴 结膜充血、眼球突出、眼睑水肿眼眶MRI、CT 或超声检查有助于诊断 • ⑤Graves 眼病：属于自身免疫性甲状腺病表现为自限性眼外肌无力、眼睑退 缩不伴眼睑下垂眼眶CT 显示眼外肌肿胀甲功提示甲状腺功能亢进或减退抗 TSH 受体抗体TRab阳性或滴度高于界值 • ⑥Meige 综合征：属于锥体外系疾病表现为单侧或双侧眼睑痉挛、眼裂变小 伴有面、下颌和舌肌非节律性强直性痉挛服用多巴胺受体拮抗剂或局部注射A 型肉毒毒素治疗有效

病面容。咀嚼肌受累可致咀嚼困难。咽喉肌受累出
鼓腮漏气、眼睑闭合不全、鼻唇沟变浅、苦笑或呈肌
重，活动后加重、休息后可减轻。眼外肌无力所致对
加重，休息和应用胆碱酯酶抑制剂后症状明显缓解、
导。其主要临床表现为骨骼肌无力、易疲劳，活动后
免疫性疾病。极少部分ＭＧ患者由肌肉特异性酪氨
ＭＧ在各个年龄阶段均可发病。在４０岁之前，女性
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一文搞定常见重症肌无力严重程度量表2016-05-31 来源：医脉通重症肌无力严重程度量表 QMGS MGC MMS ARS-MG重症肌无力（Myasthenia gravis，MG）是一种神经肌肉接头疾病，通过评分量表，可以对患者的病情严重程度进行定量评估，从而更为直观地评价患者病情，有助于进行临床观察、判断药物疗效。

评价重症肌无力严重程度的量表多种多样，本文将对4种常见的量表进行介绍，以期对临床实践有所帮助。

（以下量表点击后可查看大图）重症肌无力定量评分（QMGS）该量表于2000年由美国重症肌无力协会提出[1-2]，完成完整量表所需时间约25分钟，使用时需要测试设备辅助，包括手持握力计和秒表计时。

条目数：13个总分：0～39分病情评估：得分越高提示病情越重重症肌无力复合量表（MGC）与其它量表相比，该量表较为“年轻”，由Burns等人于2010年提出[3]。

该量表的完成时间所需时间少于5分钟，特点是需要医生检查与患者病史相结合。

条目数：10个总分：0～50分病情评估：得分越高提示病情越重肌无力肌肉量表（MMS）该量表由Gajdos等人研制，于1997年正式发表于神经病学年鉴杂志[4]。

需要注意的是，与其它量表相比，该量表无呼吸肌相关评估内容。

条目数：9个总分：0～100分病情评估：得分越高提示病情越轻重症肌无力绝对和相对评分法（ARS-MG）该量表为我国许贤豪教授设计，于1997年发表[5]，现被用于《重症肌无力诊断和治疗中国专家共识》2012版，以及《中国重症肌无力诊断和治疗指南》2015版。

量表分为绝对评分和相对评分两部分，其中相对评分为通过公式计算得出。

条目数：8个总分：0～60分病情评估：得分越高提示病情越重量表简评目前已有多种工具用于评价MG的严重程度，根据高翔等人的研究[6]，上述4种严重程度量表信度和效度良好，均能可靠有效地评价MG的严重程度。

不同的量表特点和优势也有所差异，ARS-MG为我国自主设计，更适用于我国患者群体，但国外的量表同样有值得借鉴之处，临床上可根据评价内容、量表详略程度及使用目的做出选择。

中国重症肌无力诊断和治疗指南2015
重症肌无力(myasthenia gravis，MG)是一种由乙酰胆碱受体(AChR)抗体 介导、细胞免疫依赖、补体参与，累及神经肌肉接头突触后膜，引起神经 肌肉接头传递障碍，出现骨骼肌收缩无力的获得性自身免疫性疾病。极少 部分MG患者由肌肉特异性酪氨酸激酶(muscle specific tyrosine kinase， MuSK)抗体、低密度脂蛋白受体相关蛋白4(low–density lipoprotein receptor–related protein 4，LRP4)抗体介导。
⑤多发性肌炎：多种原因导致的骨骼肌间质性炎性病变，表现为进行性加重 的弛缓性肢体无力和疼痛。肌电图示肌源性损害。心肌酶显著升高、肌肉活 检有助于诊断。糖皮质激素治疗有效。
⑥肉毒中毒：为肉毒杆菌毒素累及神经肌肉接头突触前膜所致，表现为眼外 肌麻痹、瞳孔扩大和对光反射迟钝，吞咽、构音、咀嚼无力，肢体对称性弛 缓性瘫痪，可累及呼吸肌，可伴有Lambert–Eaton综合征样的自主神经症 状。肌电图示低频RNS无明显递减，高频RNS可使波幅增高或无反应，取决 于中毒程度。对食物可进行肉毒杆菌分离及毒素鉴定。
⑦代谢性肌病：肌肉代谢酶、脂质代谢或线粒体受损所致肌肉疾病，表现为 弛缓性肢体无力，不能耐受疲劳，腱反射减低或消失，伴有其他器官受损。 肌电图示肌源性损害。心肌酶正常或轻微升高、肌肉活检和基因检测有助于 诊断。
一般治疗
一、胆碱酯酶抑制剂治疗 此类药物是治疗所有类型MG的一线药物，用于改善临床症状，特别是新近
②慢性炎性脱髓鞘性多发性神经病：免疫介导的慢性感觉运动周围神经病， 表现为弛缓性肢体无力，套式感觉减退，腱反射减低或消失。肌电图示运动 或感觉神经传导速度减慢、波幅降低和传导阻滞。脑脊液有蛋白–细胞分离 现象，周围神经活检有助于诊断。

Myasthenia gravis:Association of British Neurologists ’management guidelinesJon Sussman,1Maria E Farrugia,2Paul Maddison,3Marguerite Hill,4M Isabel Leite,5David Hilton-Jones 5▸Additional material ispublished online only.To view please visit the journal online (/10.1136/practneurol-2015-001126)1Department of Neurology,Greater ManchesterNeuroscience Centre,Salford,Greater Manchester,UK 2Institute of Neurological Sciences,Southern General Hospital,Glasgow,UK 3Department of Neurology,Nottingham University Hospitals NHS Trust,Queens Medical Centre,Nottingham,Nottinghamshire,UK 4Department of Neurology,Morriston Hospital,Swansea,Wales,UK 5Department of Neurology,John Radcliffe Hospital,Oxford,UK Correspondence toDr Jon Sussman,Department of Neurology,Greater Manchester Neuroscience Centre,Stott Lane,Salford,Greater Manchester,M68HD,UK;Jon.sussman@ Accepted 13April2015ABSTRACTMyasthenia gravis is an autoimmune disease of the neuromuscular junction for which many therapies were developed before the era ofevidence based medicine.The basic principles of treatment are well known,however,patients continue to receive suboptimal treatment as a result of which a myasthenia gravis guidelines group was established under the aegis of The Association of British Neurologists.These guidelines attempt to steer a path between evidence-based practice whereavailable,and established best practice where evidence is unavailable.Where there isinsufficient evidence or a choice of options,the guidelines invite the clinician to seek the opinion of a myasthenia expert.The guidelines support clinicians not just in using the right treatments in the right order,but in optimising the use of well-known therapeutic agents.Clinical practice can be audited against these guidelines.These guidelines are designed to guide physicians and general neurologists in the management of myasthenia gravis.They are based on evidence where available,and on the experience of experts where well-established treatments lack evidence.It is not possible to consider all the potential decisions in managing myasthe-nia without resorting to opinion rather than evidence.i These guidelines thereforedirect the physicians to seek the advice of a neurologist with a specialist interest in myasthenia where the evidence base is too limited,where there is a range of treatment options or when the disease is difficult to manage.Myasthenia gravis symptoms vary ,and so patients should be managed as far as possible by one clinician.A myasthenia specialist nurse or neuromuscular advisor,if available,should be involved in the care of patients.All patients should receive the contact details of their named clinician in case of clinical deterioration and should be aware of patient information literature available from Myaware (previously the Myasthenia Gravis Association).iiThe UK Medicines and Healthcare Products Regulatory Agency regularly updates its advice on the use of a range of medication.Please refer to contempor-aneous advice on the uses and interac-tions of the medications discussed in these guidelines.These guidelines can only offer sugges-tions on how to treat common clinical scenarios.This document is intended to offer guidance:it could be followed to the letter or used flexibly .Individuals with myasthenia vary ,so it is assumed that clinicians will select therapy accordingly .iiiA completed AGREE questionnaire relevant to these guidelines is availableiThere are remarkably few studies comparing treatments in myasthenia gravis.Some were established before the era of evidence-based medicine.Some pivotal positive treatment studies used only small numbers,and their flawed design may account for studies suggesting that a commonly used medication (mycophenolate mofetil)lacks efficacy .For these reasons,these guidelines provide practical advice on starting standard treatment but avoid giving authority to non-evidence-based opinion by suggesting that expert opinion is sought where evidence is lacking,such as in the choice of immunosuppressive agents.iiMyaware.College Business Centre,Uttoxeter New Road,Derby ,UK DE223WZ tel:+441332290219.W ebsite at http://www /(accessed 23Mar 2015).iiiThe same errors in myasthenia management occur repeatedly .These include a misplaced faith in the benefits of pyridostigmine,and reluctance to use sufficient doses of prednisolone to induce remission.12Sussman J,et al .Pract Neurol 2015;15:199–206.doi:10.1136/practneurol-2015-001126199on the Practical Neurology website(see online supple-mentary appendix).INVESTIGATIONS,INITIAL ASSESSMENT AND DIAGNOSISDiagnostic tests1.Serum anti-acetylcholine receptor(ACh-R)antibodytesting:first-line investigation for non-urgent patients.2.Thyroid function:for all patients.iv3.Serum anti-muscle-specific kinase(MuSK)antibodytesting:for all patients negative for ACh-R antibodies. 4.Neurophysiology:May help to establish the diagnosis inseronegative patients with suspected myasthenia gravis.It should be performed by a practitioner with experience of myasthenia gravis.Repetitive nerve stimulation is the initial test;if negative,consider single-fibre electromyo-graphy.v Focus the testing on symptomatic muscles.5.MR scan of brain:Patients with negative serology andneurophysiology,and symptoms compatible with ocular myasthenia may have structural brain disease.6.Thymus scanning:All patients with suspected myasthe-nia,irrespective of distribution(ocular/generalised)or serology(seropositive/negative),should undergo thymus imaging.The modality(CT or MRI)should be decided locally.7.Referral to a myasthenia specialist:If tests are negativeand myasthenia is still suspected or if a congenital myas-thenia syndrome is suspected.8.Edrophonium/T ensilon test.If there is diagnostic doubt,refer to a myasthenia gravis specialist.viConfirmation of diagnosis and subtypeACh-R/MuSK seropositive/seronegativeThymoma/no thymoma viiOcular viii/generalisedCongenital:(may mimic seronegative autoimmune myasthenia)Possible myasthenia but tests negative:consider a muscle disorder or refer to myasthenia expert for management.INITIAL TREATMENT PLAN▸Choose inpatient care:For significant bulbar symptoms early on,low vital capacity,respiratory symptoms or pro-gressive deterioration.▸Choose outpatient care:For ocular symptoms,mild-to-moderate limb weakness and mild bulbar symptoms.▸Ocular myasthenia gravis:See section‘T reatment of ocular myasthenia gravis’.▸Generalised myasthenia gravis:See section‘T reatment of generalised myasthenia gravis’.TREATMENT OF OCULAR MYASTHENIAGRAVIS ix xStarting treatment for ocular myasthenia gravis xi1.Start pyridostigmine following protocol.See section‘Pyridostigmine dose escalation protocol’.2.If the serum ACh-R antibody is positive and the patientis aged under45years:consider thymectomy at presentation.xii xiii3.If symptomatic despite pyridostigmine,start prednisol-one(generally given on alternate days)xiv See section ‘Protocol for starting prednisolone for outpatients with ocular myasthenia gravis’.4.If symptoms relapse on prednisolone withdrawal at adose of7.5–10mg/day(or15–20mg alternate days)or greater,consider immunosuppression.xv See sections ‘Patients who do not achieve remission with prednisol-one’and‘Immunosuppression’.iv Other autoimmune diseases are more common in patients with myasthenia gravis;thyroid dysfunction that may otherwise be occult may exacerbate myasthenia.B12deficiency is more common inpatients with myasthenia gravis and may cause changes in the fullblood count,including a rising mean corpuscular volume andfalling white count(mimicking the effect of azathioprine).For practical management of myasthenia gravis,measuring B12can help. v Single-fibre electromyography lacks specificity.It helps in the clinical setting of myasthenia but may be positive in a wide range ofother settings,such as denervation and myopathic disorders.It should therefore be carried out only by neurophysiologists with experience in neuromuscular transmission disorders.vi The edrophonium test may be difficult to interpret.Conditions that mimic myasthenia may produce a positive result and there are potential cardiac complications.If serology and neurophysiology still give no diagnosis,seek a specialist opinion.vii Thymic hyperplasia is a pathological diagnosis and cannot be evaluated by scanning.The scan is done solely to exclude thymoma. viii Note that most patients with ocular myasthenia develop generalised myasthenia within about two years.ix The recently published EFNS/ENS Guidelines3offer identical advice.x There is little evidence for the pyridostigmine and prednisolone dose schedules recommended here;there are no studies comparing treatment regimens.These guidelines are based on the practice of experts in the field.The emphasis is on identifying the optimum dose for each patient.Undertreatment,particularly with corticosteroids,is the commonest cause of persisting symptoms.xi Around50%of patients with ocular myasthenia develop generalised myasthenia within2years and up to75%do so within 3years or so of disease onset.This is more likely in the seropositive group.xii Many experts consider thymectomy,and particularly the less traumatic and scar-minimising video-assisted thoracoscopic thymectomy in a young person with seropositive generalised myasthenia gravis.Some experts consider video-assisted thoracoscopic thymectomy in purely ocular myasthenia gravis. Thymectomy is probably most effective if carried out early on,say 2years after symptom onset.Thymectomy probably does not help established ocular myasthenia gravis where there is little risk of generalisation.xiii Offering video-assisted thoracoscopic thymectomy even before starting corticosteroids may be an option for some patients.As thymectomy produces benefit slowly,this is appropriate only for patients with mild disease.xiv An alternate day corticosteroid regimen probably reduces side effects.Daily corticosteroids may be suitable in some patients,such as those with diabetes mellitus.xv In principle,immunosuppression is only started following relapse induced by corticosteroid withdrawal.In some patients with complex medical problems,higher doses of corticosteroids may be preferable to immunosuppression,or vice versa.It is impossible to provide absolute guidance on the target corticosteroid dose.In some patients,even low-dose corticosteroids cause side effects; these might be treated with immunosuppression.Exceptional cases should be discussed with a myasthenia expert.200Sussman J,et al.Pract Neurol2015;15:199–206.doi:10.1136/practneurol-2015-001126Pyridostigmine dose escalation protocol xvia,xvibTitrate up to find the lowest effective dose:▸Initially30mg(½tablet)four times daily for 2–4days.▸Then60mg(1tablet)four times daily for5days and experiment with timing.▸Then increase to90mg four times daily over 1week if required.The duration of action varies, and some patients require five divided daily doses.If pyridostigmine does not control symptoms satis-factorily within a few weeks,start prednisolone. Management of side effects:Propantheline or mebe-verine can help cholinergic side effects. Withdrawal:▸If using pyridostigmine monotherapy,prescribe the lowest effective dose.▸If asymptomatic following introduction of prednisol-one only,withdraw slowly at30–60mg per week,until either withdrawn,or use the lowest effective dose.Protocol for starting prednisolone for outpatients with ocular myasthenia gravis xviiStart5mg on alternate days xviii for three doses and increase by5mg every three doses until symptoms improve.The maximum dose is50mg on alternate days or0.75mg/kg/alternate day for ocular myasthe-nia gravis.Clinical remission of myasthenia on corticosteroid treatment is defined as the absence of symptoms and signs after pyridostigmine withdrawal.Some patients are resistant to corticosteroids or respond very slowly.After3months of treatment, non-responders should be referred to a myasthenia specialist.Prednisolone may either induce or exacerbate dia-betes mellitus.This should be monitored.xix Daily rather than alternate day prednisolone may improve glycaemic control in patients taking treatment for ele-vated plasma glucose.Bone protection protocol for patients treated with corticosteroidsUse local agreed guidelines.Prednisolone withdrawal for ocular myasthenia gravis xi Prednisolone should be titrated down,seeking the lowest effective dose,only after achieving remission (absence of symptoms and signs having withdrawn from pyridostigmine)for at least2–3months:▸Reduce by5mg alternate day/calendar month down to 20mg alternate days.▸Then reduce by2.5mg alternate day/calendar month down to10mg alternate days.▸Below10mg alternate days reduce by1mg/month.See section‘Corticosteroid maintenance dose and criteria for introducing immunosuppression’for target dose.▸Should symptoms recur,follow guidance for myasthenic relapse(see section‘Assessment and management of the relapsing patient with myasthenia).Corticosteroid maintenance dose and criteria for introducing immunosuppression▸A prednisolone dose above15–20mg on alternate days is probably too high for long-term use,and is an indication to introduce immunosuppression with azathioprine.xx▸Intolerable corticosteroid side effects are an indication to introduce immunosuppression to reduce the corticoster-oid maintenance dose.TREATMENT OF GENERALISED MYASTHENIA GRAVIS xxiStarting treatment for generalised myasthenia gravis1.Start pyridostigmine following protocol.See section‘Pyridostigmine dose escalation protocol’.2.ACh-R antibody seropositive and aged under45years:consider thymectomy.xxiixvia Use pyridostigmine carefully in patients with obstructive respiratory disease,brady-dysrhythmias,impaired renal function and recent coronary occlusion.xvib The drug information sheet specifies that propantheline is contraindicated in myasthenia gravis:this is not correct as it is astandard treatment for the side effects of pyridostigmine.xvii The evidence suggests that the biggest error in managing myasthenia is the failure to induce remission in a timely manner using corticosteroids.There is a tendency to try to avoid using large doses of corticosteroids.If it is tolerated,the top dose is prednisolone0.75mg/kg for ocular disease.Corticosteroid-induced deterioration in myasthenia sometimes occurs.It is particularly associated with starting high-dose corticosteroids.It can occur in patients adhering to the dose regimen recommended in these guidelines,though it may also be confused with the deterioration in symptoms that continues until the benefit from corticosteroids becomes apparent,often within a week or two.If in doubt,seek expert advice.xviii The side effects are probably minimised by using alternate day dosing.xix Patients with known diabetes mellitus should be monitored following the introduction of corticosteroids.Experts are aware of non-diabetic patients who developed diabetes mellitus,sometimes months after starting prednisolone.It is beyond the scope of these guidelines to offer specific guidance in this area.Local guidelines should be used.xx There is little hard evidence on the absolute safest long-term dose of corticosteroids.Since a component of the complications can be managed by bone protection,and blood pressure and lipid management,there may be individual cases with other health problems,in whom higher doses of maintenance corticosteroids would be better than immunosuppression.In principle,however, failure to control myasthenia symptoms with a‘safe’dose of corticosteroids is the main indication for starting immunosuppression.xxi There is little evidence for the pyridostigmine and prednisolone dose schedules recommended here and there have been no studies comparing treatment regimens.These guidelines are based on the practice of experts in the field.The emphasis is on identifying the optimum dose for each patient.Undertreatment,particularly with corticosteroids,is the commonest cause of persisting symptoms.xxii Many experts consider thymectomy,particularly the less traumatic and scar-minimising video-assisted thoracoscopic thymectomy in a young person with seropositive generalised myasthenia gravis.Thymectomy appears most effective if carried out early on,say2years after symptom onset.Sussman J,et al.Pract Neurol2015;15:199–206.doi:10.1136/practneurol-2015-0011262013.If symptomatic despite pyridostigmine,start prednisol-one(generally given on alternate days)xxiii See section ‘Protocol for starting prednisolone for outpatients with generalised myasthenia gravis’.4.If relapse occurs on prednisolone withdrawal at a dose of7.5–10mg/day(or15–20mg alternate days)or greater,introduce immunosuppression.xxiv Immunosuppression may also be used for patients with corticosteroid-related side effects on low-dose prednisolone.xxv See sections ‘Patients who do not achieve remission with prednisol-one’and‘Immunosuppression’.Pyridostigmine dose escalation protocol xxviTitrate up to find the lowest effective dose:▸Initially30mg(½tablet)four times daily for2–4days.▸Then60mg(1tablet)four times daily for5days and experiment with timing.▸Then increase to90mg four times daily over1week if required.The duration of action varies,and some patients require five divided daily doses.If pyridostig-mine fails to control symptoms satisfactorily within a few weeks,start prednisolone.Management of side effects:propantheline xxvi or mebeverine can help cholinergic side effects. Withdrawal:▸If using pyridostigmine monotherapy,prescribe the lowest effective dose.▸If asymptomatic after introduction of prednisolone only, withdraw slowly at30–60mg per week,until with-drawn,or use the lowest effective dose.Protocol for starting prednisolone for outpatients with generalised myasthenia gravis xxviiStart10mg on alternate days xxviii for three doses and increase by10mg every three doses until symptoms improve.Maximum dose is100mg alternate days or 1.5mg/kg for generalised myasthenia gravis.It may take many months to achieve full remission. Remission of myasthenia on corticosteroid therapy is defined as the absence of symptoms and signs after pyridostigmine withdrawal.For failure to respond,or side effects on increasing corticosteroids,seek expert opinion for guidance on the use of plasma exchange,intravenous immunoglobulin or immunosuppression.If not in remission after3months of corticosteroid treatment,refer for expert opinion. Prednisolone may induce or exacerbate diabetes mellitus.This should be monitored.xxix Using daily rather than alternate day prednisolone may improve glycaemic control in patients taking treatment for ele-vated plasma glucose.Bone protection protocol for patients treated with corticosteroidsUse local agreed guidelines.Protocol for withdrawal of prednisolone for generalised myasthenia gravis xxx▸Prednisolone should be titrated down seeking the lowest effective dose only after achieving remission(absence of symptoms and signs having withdrawn pyridostigmine) for at least2–3months.▸Reduce by10mg/calendar month down to40mg on alternate days.▸Then reduce by5mg/calendar month down to20mg on alternate days.▸Then reduce by2.5mg per calendar month down to 10mg alternate days.▸Below10mg alternate days,reduce by1mg/month, aiming for a maintenance dose of7or8mg.▸Should symptoms recur,follow guidance for myasthenic relapse(see section‘Assessment and management of the relapsing patient with myasthenia’).Corticosteroid maintenance dose and criteria for starting immunosuppression▸A corticosteroid dose above15–20mg on alternate days is probably an indication to introduce alternative immunosuppression with azathioprine.xxxixxiii An alternate day regimen is thought to reduce side effects.Daily corticosteroids may be suitable in some patients,such as those with diabetes mellitus.xxiv In principle,other than in exceptional circumstances, immunosuppression is not started other than following relapse induced by corticosteroid withdrawal.Some patients with complex medical problems,higher doses of corticosteroids may be preferable to immunosuppression,or vice versa.Exceptional cases should be discussed with a myasthenia expert.xxv It is impossible to provide absolute guidance on minimum corticosteroid requirements.There will be some patients in whom even low-dose steroids cause side effects,and who might be treatedwith immunosuppression.There may be good reasons why other patients are treated with a slightly higher than recommended prednisolone dose in preference to immunosuppression.Exceptions should be discussed with a myasthenia expert.xxvi Pyridostigmine should be used carefully in patients with obstructive respiratory disease,brady-dysrhythmias,impaired renal function and recent coronary occlusion.The drug information sheet specifies that propantheline is contraindicated in myasthenia gravis:this is incorrect as it is a standard treatment for the side effects of pyridostigmine.xxvii The evidence suggests that the biggest error in managing myasthenia is not inducing remission in a timely manner using corticosteroids. Clinicians tend to try to avoid using large doses of corticosteroids.If the patient tolerates these,the top dose is prednisolone0.75mg/kg for ocular disease and1.5mg/kg for generalised myasthenia gravis. Corticosteroid-induced deterioration in myasthenia may sometimes occur.This can be confused with the ongoing deterioration in symptoms that continues until the corticosteroids start to help,often within a week or two.If in doubt,seek expert advice.xxviii Alternate day dosing probably minimises side effects.xxix W e recommend monitoring patients with known diabetes mellitus after starting corticosteroids.Occasionally,non-diabetic patients develop diabetes mellitus,sometimes months after starting prednisolone.It is beyond the scope of these guidelines to offer specific guidance for blood glucose monitoring;local guidelines should be used.xxx This is the typical rate of corticosteroid reduction.If there are other factors,such as serious side effects,the corticosteroids might be withdrawn more rapidly.Discuss with a myasthenia expert.xxxi There is little hard evidence on the absolute safest long-term dose of steroids.Since a component of the complications can be managed by bone protection,and blood pressure and lipid management,there may be individual cases with other health problems,in whom higher doses of maintenance steroids would be preferable to immunosuppression.In principle,however,failure to control myasthenia symptoms with a‘safe’dose of corticosteroids is the primary indication for the initiation of immunosuppression.202Sussman J,et al.Pract Neurol2015;15:199–206.doi:10.1136/practneurol-2015-001126▸Intolerable corticosteroid side effects are an indication to introduce immunosuppression to reduce the corticoster-oid maintenance dose.PATIENTS WHO DO NOT ACHIEVE REMISSION WITH PREDNISOLONEPatients who do not achieve symptom remission on the prednisolone escalation protocol▸Some patients appear to fail to respond to the recom-mended doses of prednisolone.This may result from a slow response to corticosteroids,which may take up to 3months and sometimes much longer.▸The commonest reason for a patient to fail to respond to corticosteroids is using an insufficient dose.xxxii▸If a patient does not respond adequately to the target dose after3months,seek a specialist opinion.IMMUNOSUPPRESSIONCorticosteroid maintenance dose and criteria for introducing immunosuppression▸W e recommend that an immunosuppressive agent is introduced only if a patient does not achieve remission on corticosteroid monotherapy.xxxiii▸A corticosteroid dose above15–20mg on alternate days is probably unacceptable for long-term use.xxxiv▸Intolerable corticosteroid side effects are an indication to introduce immunosuppression to reduce the corticoster-oid maintenance dose.▸Immunosuppression should be considered early on in patients with diabetes mellitus,osteoporosis,or ischaemic heart disease or significant bulbar or respiratory weakness that does not respond rapidly to corticosteroids.▸Immunosuppression and vaccination:V accines are less effective in immunosuppressed patients.Live vaccines are absolutely contraindicated and there is an increased risk from live-attenuated vaccines.Patients requiring immuno-suppression should have their vaccinations updated.This might include pneumococcus,influenza,Haemophilus influenzae and Varicella zoster.xxxv Where feasible,clini-cians should plan vaccinations(with blood tests to assess response)before starting immunosuppression.▸Corticosteroids in high doses can reduce the immune response to vaccines and live virus vaccinations should be delayed for at least1month after stopping high-dose corticosteroids.Immunosuppression with azathioprine xxxvi▸Azathioprine is the first-line agent.Thiopurine methyl-transferase(TMPT)should be measured in view of the association between TMPT deficiency and myelosuppres-sion with azathioprine.TMPT deficiency is not a contra-indication to using azathioprine but may reduce the dose required.xxxvii Patients with very low TMPT activity should not take azathioprine.▸Azathioprine should be increased over1month to a maintenance dose of2.5mg/kg.Blood tests should be monitored weekly(full blood count,urea and electro-lytes,liver function tests)as the dose is titrated upwards.xxxviii The dose may need to be modified in light of side effects or changes in blood tests.W e recom-mend using local shared-care protocols.▸Azathioprine is slow to achieve maximum effect.xxxix The target is to achieve a maintenance dose of prednisol-one of below20mg on alternate days after2years.Failure to achieve efficacy may be a consequence of inad-equate dosing.Not all patients respond to azathioprine.Corticosteroids should be withdrawn using the protocol described.xlxxxii A good source of ideas if things do not proceed according to plan is Hilton-Jones.2xxxiii The pivotal paper that showed the corticosteroid-sparing effect of azathioprine4has been interpreted as suggesting that all patients require immunosuppression to achieve a safe maintenance dose of prednisolone.However,many patients who achieve remission can be maintained on low-dose prednisolone without needing immunosuppression.There is no evidence-based way to identify patients who will fail to achieve remission on corticosteroid monotherapy,so it should be attempted in all.xxxiv There is little hard evidence on the absolute safest long-term dose of corticosteroids.Since a component of the complications can be managed by bone protection,and blood pressure and lipid management,there may be individual cases with other health problems,in whom higher doses of maintenance steroids would be preferable to immunosuppression.In principle.however,failure to control myasthenia symptoms with a‘safe’dose of corticosteroids is the primary indication for the initiation of immunosuppression. xxxv Local or national guidelines should be followed.xxxvi There is a range of immunosuppressive agents that can be successfully used in myasthenia despite the lack of robust evidence for their use.All studies are underpowered or suffer from design faults.The criteria for selecting agents might include safety in pregnancy,time to onset of efficacy and risk of complications, although there is often a lack of evidence in these areas.In practice, we recommend that non-experts manage patients with corticosteroids to induce remission,and use azathioprine as a corticosteroid-sparing agent.If this fails,then the patient should be referred to a myasthenia expert to advise on alternative immunosuppressive agents.xxxvii Note that TMPT levels will be modified in patients who have received blood products.Patients with low serum TMPT concentrations can be treated with lower doses of azathioprine. Some experts recommend using a dose of25mg once daily.In view of the evidence from other conditions that correlates efficacy with a rise in mean corpuscular volume and/or a drop in peripheral lymphocyte count,others titrate the dose up until there is a haematological response.6-thioguanine nucleotides(6-TGN),which are incorporated into DNA,are the active metabolites of azathioprine.6-TGN has started to be used to monitor compliance and toxicity.It is not widely available but can be used to guide dosing.xxxviii In rheumatological and gastroenterology patients,azathioprine efficacy correlates with a drop in lymphocyte count and/or an elevation in mean corpuscular volume.In inflammatory bowel disease,macrocytosis appears to be the better marker.There is no evidence in myasthenia,but anecdotal observations suggest that a failure to respond to azathioprine is more common in patients without a change in these indices.W e recommend treating using the initial mg/kg dosing,and following local shared-care protocols.A specialist opinion should be sought if difficulties arise.xxxix The pivotal azathioprine study4showed efficacy at2years but not at1year.It is likely that this varies between patients.xl A patient taking100mg alternate day prednisolone would take 14months to reduce to a safe maintenance dose.Sussman J,et al.Pract Neurol2015;15:199–206.doi:10.1136/practneurol-2015-001126203。