ACRVM  >> Vol. 7 No. 3 (August 2019)

    反复经颅磁安慰治疗卒中后抑郁的研究停顿
    Advances in Research of Repetitive Transcranial Magnetic Stimulation for Post-Stroke Depression

  • 全文下载: PDF(824KB) HTML   XML   PP.50-56   DOI: 10.12677/ACRVM.2019.73009  
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作者:  

武军祥,师 宁,李梦园,刘 杰:延安大年夜学从属医院,陕西 延安

关键词:
反复经颅磁安慰卒中后抑郁研究停顿综述 Post-Stroke Depression Research Progress Review

摘要:

卒中后抑郁(Post Stroke Depression, PSD)为神经功能缺损后而至的以耐久且明显的心境降低为主,可伴随睡眠妨碍、焦炙、心境改变、认知妨碍等一系列临床表示的疾病,可直接影响患者神经康复和精力心思稳定,抑郁改变严重增长卒中后患者的住院率、致残率和逝世亡率。惯例重要为抗抑郁药物治疗,和心思治疗等帮助手段,但抗抑郁药有时对PSD患者获益较小或有效,甚者副感化等倒霉身分招致疾病生长好转。近年来,反复经颅磁安慰(Repetitive transcranial magnetic stimulation rTMS)以其副感化少、疗效可不雅备受迎接,很多作者将此技巧应用于卒中后抑郁的治疗,以求最低的弊病促使患者最大年夜获益。经过过程查阅文献后发明此治疗手段众家看法各有所长。为此,本文重要对rTMS治疗卒中后抑郁及伴随各临床症状展开综述,分析其治疗的研究停顿,为临床任务起到能够性提示感化

Post Stroke Depression (PSD) is a long-term and significant depression caused by neurological deficits. It can be accompanied by a series of clinical manifestations such as sleep disorders, anxiety, mood changes, and cognitive disorders. It can directly affect the patient's neurological rehabilitation and mental and psychological stability. Depression changes severely increase the hospitalization rate, disability rate and mortality rate of patients after stroke. Routines are mainly anti-depressant medications, as well as psychotherapy and other ancillary means, but antidepressants sometimes benefit less or ineffective PSD patients, and even side effects such as side effects lead to disease progression. In recent years, Repetitive transcranial magnetic stimulation (TMS) has been popular in a state with few side effects and considerable curative effect. Many authors have applied this technique to the treatment of post-stroke depression in order to minimize the drawbacks that the patients are the biggest Benefit. After consulting the literature, it was found that this treatment has its own opinions. To this end, this article mainly reviews rTMS treatment of post-stroke depression and accompanying various clinical symptoms, analyzes the research progress of its treatment, and plays a role in suggesting clinical work.

1. 引言

一项全球回想性研究警示全球疾病包袱并不是乐不雅,于2016年脑卒中位居全球第二致逝世身分,总逝众人数约达550万,其高病发率以中国为主(每年354人/10万人)。标准化后病发率、逝世亡率虽有降低趋势,但随着人口增长、老龄化及卒中治疗手段的生长,急性期存活人数、慢性期管理数量和卒中而至伤残减寿年数的相对数量仍在赓续增长 [1]。急性期治疗手段已有浩大明白的证据指引,然则关于脑卒中并发症的治疗和管理依然是我们每个临床大夫不该忽视的阶段,尽早的神经功能恢复、认知功能改良和精力心思稳定能较好的进步脑卒中患者的生命质量、社会参与度,和减轻家庭、社会、国度医疗资本的经济包袱。卒中后抑郁作为脑卒中后一项多发临床症状,结合患者及家眷缺乏相干疾病的熟悉和严重性,缺乏必定的救治欲望,进而影响患者进一步康复,甚者抑郁程度占据全部疾病好转过程,招致患者自杀不雅念抢先,对家庭、社会带来弗成忽视的影响和包袱。反复经颅磁安慰(rTMS)是一种安然、无创伤、无苦楚悲伤的新型治疗技巧,对治疗心境妨碍、帕金森等疾病,取得较好成果,且经美国于2007年FDA赞成认证为一种新型抗抑郁办法 [2]。

2. 反复经颅磁安慰治疗PSD的机制

2.1. 心思学机制

2.1.1. Ca2+依附性调理

rTMS启动神经元中的举措电位和(或)改变神经元程度安慰时代的神经高兴性,还能够经过过程对引诱膜的润饰表示出其对静息电位和阈值的感化,特别对通道特点改变细胞门控组件的活动、突触连接和(或)时序静态。rTMS可对Ca2+动力学的变更和Ca2+依附性酶的激活,调理谷氨酸AMPAr/NMDAr的表达,和即刻早期基因的引诱 [3] [4]。

2.1.2. 神经递质释放性调理

急性rTMS明显增长大年夜鼠中5-HT1A受体的表达前额叶和扣带皮层,但其实不会招致5-HT量的明显变更 [5]。慢性rTMS,降低突触前5-HT1B和5-HT1A本身受体的敏理性有助于进一步增长突触间隙的5-HT程度。在人类中,脑TMS-SPECT病例对比研究注解r TMS治疗有影响5-羟色胺能体系,特别是在左背外侧前额叶皮质上的HF (10 Hz) rTMS [5]。

2.1.3. 参与神经养分因子程度性调理

神经养分因子(NTs)构成一个主动调理突触可塑性蛋白质的家族,促进神经元存活和分化,但也促进细胞凋亡。在AD大年夜鼠模型中,低频rTMS经过过程上调海马NGF,BDNF和NMDAr的表达来逆转淀粉样蛋白β1-42引诱的认知缺点。经久rTMS增长了BDNF水平和小鼠单克隆抗体的整体生计才能海马HT22细胞,从而确保对氧化应激物等的神经保护感化作为Aβ和谷氨酸 [6] [7]。

2.1.4. 对神经内渗出体系调理

安康和疾病中大年夜脑功能的调理严格依附于活动内渗出体系。对压力的心思反响须要激活交感神经肾上腺素和下丘脑-垂体-肾上腺(HPA)体系。HPA轴对神经功能的影响包含一组复杂的直接功能前额皮质(例如,DLPFC,亚系扣带,内侧PFC),下丘脑,垂体和肾上腺之间的负反应类型,还与其他脑搜集(如基底神经节)具有双向影响(例如,伏隔核,纹状体)和边沿体系(例如,海马,杏仁核)。接收MANUSCRIPT特定神经激素,神经介质和神经递质如ACTH、谷氨酸、GABA、多巴胺、5-羟色胺)。在急性应激条件下,下丘脑释放促肾上腺皮质激素释放因子(CRF)到垂体腺,激活ACTH释放然后安慰皮质醇从肾上腺释放 [8] [9]。皮质醇会影响其经过过程负反应回路停止渗生产生和大年夜脑活动,特别是在高反响区域糖皮质激素受体的密度,如额叶区和海马区。Herbert经过过程对植物研究发明皮质醇可调理神经元的发展及重塑,其持续降低对糖皮质激素受体皮层区域产生毒性感化,招致神经元细胞功能降低、变性、逝世亡 [10]。刘晓丹等对30例首发抑郁患者研究发明抑郁患者左左外侧前额叶眶回(lOFC)、左边舌回(LC)、右边前喙扣带皮层(rACC)、右边颞下回(ITC)的皮层厚度与皮质醇负相干,证明这些区域能够含有必定命目标糖皮质激素受体较易遭到高皮质醇细胞毒性感化的影响 [11]。

2.1.5. 对炎症,氧化应激和预防神经细胞逝世亡的调理

在中枢神经体系中,对外部应激源的神经炎症反响的特点在于激活小神经胶质细胞和星形胶质细胞,招致促炎症的级联释放介质(谷氨酸,ATP,IL-1β,TNFalpha)和自在基的产生,包含活性氧(ROS),反过去,其保持神经炎症反响 [12] ,这个过程被称为反响性胶质增生和随后的突触重塑,突触的破坏连接,神经递质稳态掉衡和谷氨酸高兴性毒性招致适应不良的突触可塑性 [13]。神经胶质细胞的激活是毁伤后恢复的关键步调,非侵入性安慰技巧可以代表一种调理神经胶质激活的新战略,如a-tDCS和c-tDCS引诱大年夜鼠长久激活(5~10天)的驻留小胶质细胞,调理神经干细胞的召募和增殖,参与恢复的机制脑毁伤后 [14]。关于细胞逝世亡,在血管性聪慧的大年夜鼠模型研究注解低频率rTMS调理凋亡旌旗灯号传导(Bcl-2的上调和Bax的下调表达),注解一种旨在保护突触的活动 [15]。

2.1.6. 参与神经胶质搜集的调理

突触的可塑性招致星形胶质细胞,小胶质细胞,少突胶质细胞的静态神经胶质相互感化,细胞外基质与神经元和血管。神经胶质搜集调理经过过程Ca2+依附性同步神经元放电过程 [16] 和与NMDAr依附的LTP引诱有关 [17] ,释放神经元和神经胶质之直接洽因子。在小鼠齿状回中,rTMS引诱胶质纤维酸性蛋白(GFAP)在星形胶质细胞中的转录,GFAP是参与细胞骨架的细胞骨架的中心丝(IF)蛋白构成IF搜集 [18]。大年夜多半离子通道和神经递质转运蛋白都是表达于星形细胞胞体和过程,并有助于突触体内均衡。

2.2. 病理能够性机制

本反复经颅磁安慰安慰大年夜脑对应皮层区域,安慰神经元细胞举措电位高兴状况,促进高兴性神经递质和神经养分因子释放,调理大年夜脑高兴状况以保持高兴稳定,促进受损部位神经细胞自我修复、重塑以进步机体功能。可改良大年夜脑对应区域血流,促进相互感化区域血供,促进病变区神经高兴性 [19]。增长卒中患者脑对葡萄糖的摄取和应用,进步能量供给,改良缺血再灌注、自在基等毁伤后的功能恢复 [20]。

3. 反复经颅磁安慰(rTMS)对卒中后抑郁的治疗

3.1. 对纯真抑郁的治疗

Robinson报导提示30%~35%脑卒中患者可在第一年内产生PSD,且在未予治疗下病发率、致残率更高 [21]。Xin等一项荟萃分析中,指出阳性成果注解rTMS具有对PSD的有益影响。但其异质性和潜伏的成见,应慎言其成果 [22]。另外一项研究将反复经颅磁安慰(rTMS)作为卒中后抑郁(PSD)患者的附加疗法研究中显示后果客不雅。从张婧,刘超猛等不合meta分析中指出rTMS可较为明显的改良PSD前后抑郁症状,进步生活质量,且不良反响相对小,未见其严重特点 [23] [24]。关于rTMS治疗时代不合频率限制亦有不合看法,根据杨柳,杨琪各自meta分析指出,在治疗4周后,高频治疗比拟低频治疗后果会更显组,且安然有效 [25] [26] ,但据Liu等研究发明虽高频治疗对抑郁有明显正效应,比拟对比组头痛则更容易出现 [27]。亦有报导rTMS结合高压氧、有氧活动等对PSD有较好的感化,且未产生不良反响,允从性较好,治疗相对安然、可行和耐受 [27] [28] [29]。

3.2. 关于PSD伴随睡眠妨碍的治疗

文献报导约有34%~76%的卒中后患者可致不合程度的抑郁状况,而其可直接影响PSD患者睡眠质量 [30]。睡眠妨碍已成为卒中后患者罕见继发改变,可表示为入眠艰苦、睡眠不实或节律混乱,比拟非睡眠妨碍患者,其明显影响患者平常生活才能,且抑郁与睡眠妨碍互为影响,严重影响患者神经功能恢复 [31]。高频具有高兴皮质的功能,低频则克制高兴,但可促进5-HT和GABA释放,调理觉悟周期,促进睡眠增长 [32]。经过过程查阅文献,并未阅及外文关于PSD伴随睡眠妨碍的治疗报导,不清除数据库检索偏倚,中文数据库有此类申报。王韵喃等对120例患者随机实验中异样得出明显正效应临床意义,关于伴随睡眠妨碍的治疗报导无限,结论应慎言而定,尚且仍需进一步多中间、大年夜数据研究分析 [33]。

3.3. 关于PSD伴随活动妨碍的的治疗

脑卒中后患者在必定意义会遗留不合程度肢体偏瘫、吞咽功能等情况,严重影响患者正常生活,而抑郁情感改变患者社会交际和下出世活兴趣,偏瘫肢体缺乏康复安慰练习招致病变应对肢体掉用性萎缩,抑郁和活动妨碍互为影响,增长康复难度,降低肢体功能。外文报导对患者两侧大年夜脑M1区予以rTMS治疗有易于患者活动妨碍肢体功能康复 [34] ,rTMS可促进皮层搜集功能连接,安慰皮层功能重塑,进步功能恢复,不合频率亦有不分解果,Sasaki等团队研究指出健侧高频是优于患侧低频治疗近端肢体功能,而远端肢体如手功能恢复不如低频 [35]。外文研究将30例样本随机分派,以低频、中频、高频实验组与对比组不雅察构造发明,关于吞咽功能妨碍低频能更明显改良症状 [36]。关于PSD后伴随肢体功能妨碍、吞咽妨碍等,rTMS提示有较好的后果,然则详细的治疗形式、参数目标、频段都另有待进一步标准共鸣,以求更好的方法对患者供给有力治疗根据。

3.4. 关于PSD伴随认知妨碍的治式

脑卒中重要为血管功能妨碍招致缺血或出血激起的一系列神经脑功能妨碍,神经细胞坏逝世后弗成恢复性,可降低病发后患者在记忆、说话、思想、计算、履行功能能方面的认知改变,甚者激起血管性聪慧,严重降低患者生命质量,影响其正常生活。左边前额叶、背外侧区、右边前额叶及其背外侧戋戋域高兴性进步,可安慰神经递质释放,皮质直接洽,促进认知改良。Sato报导予以左前额叶背外侧rTMS低频安慰,可改变皮层神经高兴与克制协同效应来改良认知 [37]。Galletly对63例样本采取计算机化认知测试评价治疗前后的认知改变,评价汉密尔顿抑郁评定量表评分从基线到治疗后有明显降低,但是,当抑郁症状的变更作为协变量被包含在内时,研究进一步支撑了rTMS作为患者治疗选择的有效性和安然性。然则今朝的研究注解,rTMS没有明显的认知妨碍,认知功能的任何改良都与抑郁症状的增添有关 [38]。Rostami等回想性研究显示rTMS关于实验样本在治疗后,其记忆、履行功能、留意力和抑郁状况出现明显变换,注解rTMS能够与之相干改良抑郁症患者的认知功能 [39]。但仍需进一步大年夜数据验证以求最公道证据支撑。

4. 评论辩论

抑郁状况是缺血性卒中后最罕见的精力并发症,对幸存者的功能康复和生活质量产生很大年夜负面影响。个中约30%患者受卒中后抑郁的影响,使卒中后抑郁成为一个严重的社会和公共卫生成绩 [20]。抑郁症和中风之间存在双向接洽关系:中风增长了PSD的风险,但抑郁症又是中风的自力风险身分。PSD的病理心思学能够是多身分的,触及在心思社会苦楚的背景下各类缺血引诱的神经生物学功能妨碍的组合。几个证据注解,在急性缺血性卒中的神经炎症反响,下丘脑-垂体-肾上腺(HPA)轴的应激激活和能量代谢改变背景下的适应性反响(神经产生)受损(即线粒体功能妨碍)之间存在关系。

就今朝而言,特别是选择性5-羟色胺(5-羟基色胺,5-HT)再摄取克制剂(SSRIs)重要被证明在预防和治疗PSD方面具有临床活性,但其感化机制有待进一步研究,且不清除增长颅内出血的能够 [40]。反复经颅磁安慰(rTMS)常常被用来增长功能恢复中风患者,rTMS可以改变安慰的大年夜脑皮质部位的高兴性和沿着功能解剖学的长途构造连接 [39]。rTMS治疗是基于脑卒中后半球间均衡受损的概念 [41]。rTMS已被证明对治疗中风并发症是安然有效的。经过过程将高兴性或克制性电磁脉冲分别应用于病灶的同侧或对侧的半球,和在调理半球间通信的经胼approach体通路程度,可以优化功能性大年夜脑活动。León研究指明rTMS对卒中后招致活动妨碍,掉语症,构音妨碍,口咽性吞咽艰苦,抑郁和感知-认知缺点有明显改良 [42]。但Nam等一项经久研究中发明rTMS对活动功能没有明显影响或中风后6个月的残疾,还指出高频率rTMS不会产生耐久的(中风后6个月)中风后活动功能和残疾的改良 [43]。固然进一步大年夜样本量的随机对比临床实验还是必定,其能以推荐更高程度的证据,在广泛的基本上精确切施rTMS在卒中受试者中的应用。

综上所述,关于今朝rTMS对治疗PSD的机制还没有明白,其虽关于PSD和各类伴随症状的疗效各有不合措辞,但整体而言,疗效明显正效应结论占比高于低效应或有效能够。固然其定论尚需慎重,依然需进一步验证其结论。信赖随着迷信技巧的生长对rTMS的进一步研究摸索能较好的应用于PSD的治疗。

NOTES

*通信作者。

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武军祥, 师宁, 李梦园, 刘杰. 反复经颅磁安慰治疗卒中后抑郁的研究停顿[J]. 亚洲心脑血管病例研究, 2019, 7(3): 50-56. https://doi.org/10.12677/ACRVM.2019.73009

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