重复经颅磁刺激治疗专家共识

中国医师协会神经调控专业委员会电休克与神经刺激学组

经颅磁刺激(transcranial magnetic stimulation,TMS)由Barker等[1]于1985年创立。基于电磁感应与电磁转换原理，用刺激线圈瞬变电流产生的磁场穿透颅骨，产生感应电流刺激神经元引发一系列生理、生化反应。作为非侵入性刺激技术，TMS作用于人脑引起神经活动的改变，可检测到运动诱发电位、脑电活动变化、脑血流、代谢和大脑功能状态改变。其微观作用包括细胞膜电位、动作电位、神经递质、受体、突触、神经可塑性发生变化。

医生应掌握TMS工作原理和作用机制，并依据临床表现、实验室和影像学检查结果，设计个体化治疗方案。先根据大脑皮质功能解剖体表投影决定刺激部位，再决定刺激模式、强度、频率、间歇、疗程等。TMS适应证已经扩大到抑郁症、癫痫、神经性头痛等[2]。

1 TMS模式分类[2]

1.1 单脉冲刺激 刺激皮层拇指运动区，用于测定MEP，测定治疗能量或运动皮层功能障碍定量评估。

1.2 成对脉冲刺激 同一个线圈在数十毫秒内先后发放2个脉冲，刺激同一脑区或2个不同线圈刺激不同脑区。常用于皮层兴奋性评估。

1.3 重复脉冲刺激 按照固定频率连续发放多个脉冲的刺激模式。通常用于临床治疗和暂时性兴奋或抑制特定皮层功能区域。具体频率参数设置依治疗或研究目的而定。

1.4 爆发模式脉冲刺激 将一种固定频率脉冲嵌套在另一种固定频率脉冲中的刺激模式。常用爆发模式有爆发模式脉冲刺激(theta burst stimulation，TBS)，是将3个连续50 Hz脉冲嵌入5 Hz脉冲中。TBS序列分为2种：连续爆发模式脉冲刺激(continuous theta burst stimulation，cTBS)抑制皮层功能，间断爆发模式脉冲刺激(intermittent theta burst stimulation，iTBS)(刺激2 s，间隔8 s)兴奋皮层功能。

2 TMS治疗风险及评估[2]

癫痫及惊厥;头皮刺痛、灼热感;头颅或体腔内存在金属磁性物质(电子耳蜗、部分心脏起搏器等植入性医疗产品);听力损害;诱发癫痫或惊厥发作风险的药物。

说明：高频刺激有诱发癫痫或抽搐发作风险。但低频刺激可以用于抗癫痫治疗[3]。12岁以下患者佩戴耳塞可以最大程度上避免噪音对听力的损害。

3 重复经颅磁刺激安全操作及治疗规范

(1)重复经颅磁刺激(repetitive transcranial mag-netic stimulation，rTMS)治疗仪器属于大型用电设备，保证电压稳定、电流不会过载，避免安全隐患。

(2)签署知情同意书并完成安全筛查评估。

(3)首次治疗测定患者皮层静息运动阈值(resting motor threshold，RMT)。患者取坐位或仰卧位，使用单脉冲模式刺激利手侧(中国人多为右利手)拇指运动区皮层(M1)，刺激10次，其中5次可以诱发拇指外展肌运动(诱发拇指外展肌诱发电位达到50微幅以上)，该刺激强度能量为RMT。RMT存在个体差异，且治疗能量大小是根据RMT进行制定，是开展rTMS治疗的必要环节[4]。

(4)根据治疗目的选定rTMS强度、频率和数目。应严格限制在安全序列范围内，避免诱发癫痫风险的安全序列[4]。

(5)rTMS治疗靶点定位。

常用治疗靶点脑区定位方法有3种：①先测定M1区，可以观测到外显运动反应进行确定，之后以M1区作为参照点，沿头皮各个方向进行定位;②参照国际标准脑电电极10～20导联系统定位(图1);③借助脑影像导航技术定位。脑影像包括：全脑T1、T2结构像、各类功能像等(如脑血流、静息态、功能区激活像等)。

(6)治疗过程中不良反应的评定。

图1 国际标准脑电电极10～20导联系统定位

4 rTMS临床治疗推荐

以下内容为共识循证依据的参照标准：由欧洲神经学会联盟提出[5]。根据证据价值由高到低，分为Ⅰ～Ⅳ 4个级别。此外还参考了牛津大学循证医学中心的循证依据标准，即优先考虑系统综述中获得的证据，也列入级别Ⅰ中。文献检索截止到2017年11月PubMed数据库。

4.1 抑郁症(美国食品和药品监督管理局适应证)加拿大、新西兰、以色列、美国都已批准rTMS可以用于治疗抑郁症。rTMS可以单独或联合药物治疗。但是对于病情严重，伴有自杀观念的抑郁症患者不建议单独使用rTMS。

临床推荐1：rTMS高频刺激左背外侧前额叶(left dorsolateral prefrontal cortex,l-DLPFC)或低频刺激右背外侧前额叶(right dorsolateral prefrontal cortex,r-DLPFC)，用于抑郁症急性期疗效肯定，连续4～6周，必要时可延长治疗时间。Ⅰ级一致证据[6-8]。

临床推荐2：先前急性期rTMS治疗受益，目前复发的患者。Ⅰ级一致证据[6-8]。

临床推荐3：rTMS可作为急性期治疗获益患者的后续或维持治疗。Ⅰ级一致证据[9-10]。

临床推荐4：rTMS可以单独或联合抗抑郁药或其他精神类药物。Ⅱ级一致证据[8]。

4.2 慢性神经性或非神经性疼痛

临床推荐1：rTMS高频刺激疼痛区域对侧皮层运动区(M1)用于治疗慢性神经痛。Ⅰ级一致证据[11-17]。

临床推荐2：rTMS低频刺激枕叶用于治疗偏头痛(美国食品和药品监督管理局批准)。Ⅰ级一致证据。

临床推荐3：rTMS高频刺激l-DLPFC或运动皮层用于治疗非神经性疼痛，如纤维肌痛、复杂区域疼痛综合征Ⅰ型。Ⅱ、Ⅲ、Ⅳ级证据[18-19]。

4.3 运动障碍

临床推荐1：rTMS高频或低频刺激辅助运动皮层或运动皮层改善帕金森病运动症状。Ⅰ、Ⅱ、Ⅲ级证据[20-22]。

临床推荐2：rTMS高频刺激或低频刺激运动区M1或辅助运动区，用于治疗药物诱发震颤。Ⅲ级一致证据[23-24]。

临床推荐3：rTMS高频刺激l-DLPFC治疗帕金森病合并抑郁症。Ⅱ、Ⅲ级证据[25-30]。

临床推荐4：rTMS低频刺激运动区治疗肌张力障碍。Ⅲ级一致证据[20-21]。

4.4 中风

临床推荐1：rTMS高频刺激受累侧皮层运动区或低频刺激健侧皮层运动区，用于治疗运动区中风。Ⅱ、Ⅲ级证据[31-33]。

临床推荐2：rTMS高频或低频刺激布洛卡区，治疗运动性失语症。Ⅲ、Ⅳ级证据[34-35]。

临床推荐3：爆发模式cTBS 序列刺激左侧后顶叶皮层治疗偏侧忽略。Ⅲ级一致证据[36-37]。

4.5 癫痫

临床推荐1：rTMS低频刺激皮层癫痫灶治疗癫痫发作。Ⅱ、Ⅲ级证据[38-40]。

4.6 耳鸣

临床推荐1：rTMS低频刺激颞叶或颞顶叶皮层，高频刺激r-DLPFC治疗耳鸣。Ⅱ、Ⅲ级证据[41]。

4.7 焦虑障碍

临床推荐1：rTMS高频刺激r-DLPFC或低频刺激l-DLPFC治疗创伤后应激障碍。Ⅲ级一致证据[42-44]。

临床推荐2：rTMS低频刺激r-DLPFC和颞顶区治疗惊恐发作和广泛性焦虑。Ⅲ级一致证据[45-46]。

4.8 强迫症

临床推荐1：rTMS高频或低频刺激双侧DLPFC治疗强迫症。Ⅱ、Ⅲ级证据[47-50]。

4.9 精神分裂症

临床推荐1：rTMS低频刺激颞顶叶皮层治疗幻听。Ⅱ、Ⅲ级证据[51-57]。

临床推荐2：rTMS高频刺激l-DLPFC或双侧DLPFC改善精神分裂症阴性症状。Ⅱ、Ⅲ级证据[58-61]。

4.10 物质成瘾

临床推荐1：rTMS高频刺激l-DLPFC降低毒品渴求(心瘾)，目前证据提示没有长期效果。Ⅱ、Ⅲ级证据[62-66]。

4.11 睡眠障碍

临床推荐1：rTMS低频1Hz刺激双侧DLPFC和顶枕区域治疗睡眠障碍。Ⅱ、Ⅲ级证据[67-68]。

5 关于临床治疗特殊群体的几点说明

5.1 孕妇 磁场强度随距离迅速衰减，所以胎儿不太可能受到TMS影响。抑郁孕妇成功接受TMS治疗而胎儿未出现副作用[69-71]。临床上孕妇接受TMS治疗应避免直接刺激腰椎。作为TMS操作者的孕妇应至少远离线圈0.7 m[72]。

5.2 儿童 研究证实单脉冲和成对脉冲TMS用于儿童安全[73]。发育过程中的因素确实影响儿童接受TMS安全性：①皮质兴奋性水平(新生儿皮质兴奋性高，刺激能量过高需要注意TMS诱发癫痫可能);②囟门关闭与否(未闭要特别注意避免机械损伤)；③外耳道生长(年龄小于2岁儿童需要特别注意保护听力)。儿童年龄小于2岁慎用[2]。

6 问题与展望

以往应用TMS的最大难题是如何精准刺激靶点。Karlström等[72]和Bohning等[74]于1998年将神经导航定位系统应用于TMS，通过与fMRI/CT等影像技术结合实现了可视化TMS，结合PET、SPECT、DTI、fMRI、磁共振波谱等技术可以更好地探讨TMS的治疗机制。目前存在主要问题包括：①治疗效果的影响因素；②各类疾病作用机制；③rTMS与药物治疗的结合。

写作组长：许 毅(浙江大学医学院附属第一医院)

写作组成员

李 达(浙江大学医学院附属第一医院，执笔人)

谭立文(中南大学湘雅二医院)

刘卫青(昆明医科大学第一附属医院)

石 川(北京大学第六医院)

傅建明(嘉兴市第二人民医院)

许 毅(浙江大学医学院附属第一医院)

安建雄(中国医科大学航空总医院)

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