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低频rTMS联合作业疗法在缺血性脑卒中恢复期中的应用

作者 / Author:孔培培 陈 颖 翟清华 许梦雅 铁新琴 王 静

摘要 / Abstract:

目的 探讨低频rTMS(重复经颅磁刺激)联合作业疗法在缺血性脑卒中恢复期患者中的应用效果。方法 选取郑州大学第二附属医院2016-10—2018-06收冶的缺血性脑卒中恢复期患者98例为研究对象,按随机数字表法分为对照组(n=49)与研究组(n=49)。对照组采取作业疗法,研究组于对照组基础上采取低频rTMS,均持续干预3个月。统计2组干预前及干预3个月后认知功能(MMSE)及肢体运动功能(Fugl-Meyer)评分、运动诱导电位(MEP)、中枢传导时间(CMCT)、血清神经生长因子(NGF)、脑源性神经营养因子(BDNF)水平及执行能力(BADS)评分。结果 (1)认知及肢体运动功能:干预3个月后2组MMSE及FMA评分均较干预前增高,研究组高于对照组(P<0.05);(2)MEP及CMCT:2组MEP及CMCT均较干预前减少,研究组少于对照组(P<0.05);(3)血清神经细胞因子:2组血清NGF及BDNF水平均较干预前增高,研究组高于对照组(P<0.05);(4)执行能力:2组BADS评分均较干预前增高,研究组高于对照组(P<0.05)。结论 联合采取作业疗法及低频rTMS对缺血性脑卒中恢复期患者实施干预,可增加血清神经细胞因子含量,利于改善其认知功能与肢体运动功能,并提升其执行能力。

关键词 / KeyWords:

rTMS,作业疗法,缺血性脑卒中恢复期,NGF,BDNF,MMSE,FMA,MEP,CMCT
低频rTMS联合作业疗法在缺血性脑卒中恢复期中的应用
孔培培1) 陈 颖1) 翟清华1) 许梦雅1)△ 铁新琴2) 王 静1)
1)郑州大学第二附属医院神经康复科,河南郑州 450003  2)郑州大学第三附属医院,河南郑州 450052
基金项目:河南省科技厅科技攻关项目(编号:182102310191)
作者简介:孔培培,Email:ppkong0402@126.com
通信作者:许梦雅,Email:xumy725@163.com
 
摘要 目的 探讨低频rTMS(重复经颅磁刺激)联合作业疗法在缺血性脑卒中恢复期患者中的应用效果。方法 选取郑州大学第二附属医院2016-10—2018-06收冶的缺血性脑卒中恢复期患者98例为研究对象,按随机数字表法分为对照组(n=49)与研究组(n=49)。对照组采取作业疗法,研究组于对照组基础上采取低频rTMS,均持续干预3个月。统计2组干预前及干预3个月后认知功能(MMSE)及肢体运动功能(Fugl-Meyer)评分、运动诱导电位(MEP)、中枢传导时间(CMCT)、血清神经生长因子(NGF)、脑源性神经营养因子(BDNF)水平及执行能力(BADS)评分。结果 (1)认知及肢体运动功能:干预3个月后2组MMSE及FMA评分均较干预前增高,研究组高于对照组(P<0.05);(2)MEP及CMCT:2组MEP及CMCT均较干预前减少,研究组少于对照组(P<0.05);(3)血清神经细胞因子:2组血清NGF及BDNF水平均较干预前增高,研究组高于对照组(P<0.05);(4)执行能力:2组BADS评分均较干预前增高,研究组高于对照组(P<0.05)。结论 联合采取作业疗法及低频rTMS对缺血性脑卒中恢复期患者实施干预,可增加血清神经细胞因子含量,利于改善其认知功能与肢体运动功能,并提升其执行能力。
关键词】  rTMS;作业疗法;缺血性脑卒中恢复期;NGF;BDNF;MMSE;FMA;MEP;CMCT
中图分类号】  R743.33    【文献标识码】  A    【文章编号】  1673-5110(2019)03-0238-08  DOI:10.12083/SYSJ.2019.03.047
 
Application of low frequency rTMS combined operation therapy in patients with ischemic stroke recovery
KONG Peipei1)CHEN Ying1)ZHAI Qinghua1)XU Mengya1)TIE Xinqin2)WANG Jing1)
1)The Affiliated Hospital of Zhengzhou UniversityZhengzhou 450003,China;2)The Third Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052,China
Abstract  Objective  To investigate the effect of low frequency rTMS (repetitive transcranial magnetic stimulation) combined with occupational therapy in patients with ischemic stroke recovery.Methods  A total of 98 patients with ischemic stroke recovery in our hospital (October 2016-June 2018) were enrolled.The random number table method was used to divide them into control group (n=49) and study group (n=49).The control group was treated with occupational therapy.The study group took low-frequency rTMS on the basis of the control group and continued to intervene for 3 months.Cognitive function (MMSE) and limb motor function (Fugl-Meyer) scores,motor induction potential (MEP),central conduction time (CMCT),and serum nerve growth factor (NGF) were compared before and 3 months after intervention.Brain-derived neurotrophic factor (BDNF) levels and performance (BADS) scores were counted.Results  (1) Cognitive and limb motor function:After 3 months of intervention,the MMSE and FMA scores of the two groups were higher than those before the intervention,and the study group was higher than the control group (P<0.05);(2) MEP and CMCT:intervention 3 After the month,the MEP and CMCT of the two groups decreased compared with the intervention group,and the study group was less than the control group (P<0.05).(3) Serum nerve cytokines:the levels of serum NGF and BDNF in the two groups increased after intervention for 3 months.The study group was higher than the control group (P<0.05);(4) Execution ability:After 3 months of intervention,the BADS scores of the two groups were higher than those before the intervention,and the study group was higher than the control group (P<0.05).Conclusion Combined interventional therapy and low-frequency rTMS intervention in patients with ischemic stroke recovery can increase serum neurocytokine levels,improve cognitive function and limb motor function,and improve their ability to perform.
Key words】  rTMS;Occupational therapy;Ischemic stroke recovery;NGF;BDNF;MMSE;FMA;MEP;CMCT
 
        缺血性脑卒中为临床常见脑血管症病,患者即使经对应规范治疗,仍会遗留不同程度肢体功能障碍及神经功能缺损症状,对其日常工作及生活造成了极大影响[1-2]。同时,因缺血性脑卒中遗留不同程度功能障碍后康复时间较长,因此易导致患者出现一定程度的抑郁、焦虑等情绪,对患者身心健康状态及机体功能康复效果均造成了不利影响[3]。因此,应采取何种措施对缺血性脑卒中恢复期患者实施干预仍是研究热点。作业疗法为临床重要康复训练措施,在脑血管疾病康复中应用较广泛,其主要是选择性指导患者通过设计与利用治疗活动而提升其工作、自理和独立活动能力,以此促使其日常生活能力恢复,最大程度改善社会、心理及躯体功能[4-5]。此外,rTMS(重复经颅磁刺激)为近些年得到推广应用的神经刺激技术,具有无创性及无痛性等优势,其主要利用刺激大脑皮质可造成远隔部或局部神经元兴奋性变化,以此抑制或兴奋大脑皮质功能,已逐渐成为脑血管疾病重要康复措施[6-8]。本研究选取郑州大学第二附属医院缺血性脑卒中恢复期患者98例,探讨低频rTMS联合作业疗法应用效果。
 
1  资料与方法
1.1  一般资料 选取郑州大学第二附属医院2016-10—2018-06收冶的缺血性脑卒中恢复期患者98例,按随机数字表法分为对照组(n=49)与研究组(n=49),2组性别、年龄、病程、合并疾病、抽烟及喝酒情况等差异无统计学意义(P>0.05),具有可比性。见表1。本研究经郑州大学第二附属医院伦理委员会审批通过。
1.2  选取标准
1.2.1  纳入标准:①经MRI、CT等检查确诊为缺血性脑卒中,且疾病处于恢复期;②无交流障碍,可清楚表达主观感受;③知晓本研究,签署同意书。
1.2.2  排除标准:①存在精神障碍家族史及病史者;②存在认知功能障碍者;③存在癫痫病史者;④体内存在金属植入物者;⑤合并全身性重度感染性疾病者;⑥合并肾、肝功能障碍者;⑦合并免疫系统、内分泌系统及血液系统重度病变者。
1.3  方法
1.3.1  对照组:采取作业疗法:①第1个月重点进行基本日常生活能力训练,主要包括学习、步行、如厕、操作轮椅、剪指甲、洗澡、梳头、剃须、刷牙、洗脸、单手进餐、拄拐行走、轮椅转移、穿脱鞋袜衣裤等,3次/d,20~30 min/次;②第2个月将基本日常生活能力训练频次增加至30~45 min/次,5次/d,参照具体功能状态,逐渐增加工具性日常生活活动能力训练,主要内容包括阅读一定难度读物,参与娱乐活动、社交活动、户外行走,并进行洗衣服、洗菜、洗碗、做饭、打扫房间、整理衣服及生活用品等,30~45 min/次,5次/d;③于不影响基本日常生活能力训练前提下,重点进行工具性日常生活活动能力训练,45~60 min/次,7次/d,若训练期间患者出现疲惫等情况则适当减少训练频次、缩短时长。
1.3.2  研究组:于对照组基础上采取低频rTMS,设备选取CCY-IA型rTMS仪(武汉依瑞德公司),取半卧位或卧位,紧闭双眼,磁刺激线圈对准左侧背外侧前额叶,与头皮切面间隔0.5 cm左右,强度为80%运动阈值(MT),频率为0.5 Hz,各序列50个脉冲,每序列间隔5 s,每次包括30个序列,共28 min,1次/d,5次/周,间隔2周对MT进行1次测定,并对其治疗强度予以调整。2组均持续干预3个月。
1.3.3  检测方法:抽取空腹静脉血4mL,离心(3 000 r/min,10 min)处理,取上清液,以美国Bio-RAD公司Bio-RAD550型酶标仪与配套试剂盒经酶联免疫吸附法测定血清神经细胞因子[神经生长因子(NGF)、脑源性神经营养因子(BDNF)]水平。
1.4  观察指标  (1)统计2组认知功能及肢体运动功能评分,干预前及干预3个月后依据MMSE(简明精神状态检查量表)、FMA量表(Fugl-Meyer)对认知功能、肢体运动功能予以评估,且FMA及MMSE评分越高则恢复效果越好[9]。(2)干预前及干预3个月后统计2组运动诱导电位(MEP)、中枢传导时间(CMCT),通过肌电图诱导电位仪测定。(3)干预前及干预3个月后统计2组血清NGF及BDNF水平。(4)干预前及干预3个月后统计2组执行能力评分,依据执行缺陷综合征行为学评价表(BADS)评估,评分范围0~24分,评分越高执行能力越好[10]
1.5  统计学方法 通过SPSS 25.0统计学软件对数据进行分析,计量资料以均数±标准差(x±s)表示,行t检验,计数资料以率(%)表示,行χ2检验,P<0.05为差异有统计学意义。
 
2  结果
2.1  2组MMSE及FMA评分比较  干预前2组MMSE及FMA评分无显著差异(P>0.05),干预3个月后2组MMSE及FMA评分均较干预前增高,研究组高于对照组(P<0.05)。见表2。
2.2  2组MEP及CMCT评分比较 干预前2组MEP及CMCT无显著差异(P>0.05),干预3个月后2组MEP及CMCT评分均较干预前减少,研究组少于对照组(P<0.05)。见表3。
2.3  2组血清NGF及BDNF水平比较 干预前2    组血清NGF及BDNF水平间无显著差异(P>0.05),干预3个月后血清NGF及BDNF水平较干预前增高,且研究组高于对照组(P<0.05)。见表4。
2.4  2组BADS评分 干预前2组BADS评分间无显著差异(P>0.05),干预3个月后2组BADS评分较干预前增高,且研究组高于对照组(P<0.05)。见表5。
表1  2组一般资料比较
Table 1  General information comparison between two groups
组别 n 年龄/岁 性别 病程(月) 糖尿病 冠心病 高血压 其他 喝酒 抽烟
研究组 49 62.79±5.06 27(55.10) 22(44.90) 3.32±0.61 11(22.45) 14(28.57) 19(38.78) 4(8.16) 23(46.94) 17(34.69)
对照组 49 63.01±4.85 29(59.18)  20(40.82) 3.24±0.59 13(26.53) 11(22.45) 22(44.90) 6(12.24) 25(51.02) 14(28.57)
t/χ2值   0.22 0.167 0.66 0.221 0.483 0.377 0.446 0.163 0.425
P值   0.827 0.683 0.511 0.639 0.487 0.539 0.505 0.686 0.515
表2  2组MMSE及FMA评分比较  (x±s,分)
Table 2  Comparison of two groups of MMSE and FMA scores  (x±s,score)
组别 n MMSE评分 t P FMA评分 t P
干预前 干预3个月后 干预前 干预3个月后
研究组 49 18.57±3.04 26.01±3.24 11.722 0.000 26.11±4.23 38.43±4.01 14.796 0.000
对照组 49 19.06±2.87 24.39±3.01 8.971 0.000 25.75±4.45 33.12±3.58 9.033 0.000
t   0.820 2.564     0.410 6.915    
P   0.414 0.012     0.682 0.000    
表3  2组MEP及CMCT评分比较  (x±s,ms)
Table 3  Comparison of two groups of MEP and CMCT scores  (x±s,ms)
组别 n MEP评分 t P CMCT评分 t P
干预前 干预3个月后 干预前 干预3个月后
研究组 49 27.29±0.68 24.96±0.71 16.59 0.000 12.37±0.29 10.72±0.24 30.683 0.000
对照组 49 27.11±0.70 26.03±0.59 8.258 0.000 12.40±0.31 11.24±0.27 19.752 0.000
t   1.291 8.114     0.495 10.076    
P   0.200 0.000     0.622 0.000    
表4  2组血清NGF及BDNF水平比较  (x±s,ng/L)
Table 4  Comparison of serum NGF and BDNF levels in 2 groups  (x±s,ng/l)
组别 n NGF t P BDNF t P
干预前 干预3个月后 干预前 干预3个月后
研究组 49 6.22±0.68 13.04±1.76 25.302 0 9.25±1.08 18.69±2.02 28.849 0.000
对照组 49 6.09±0.72 8.96±1.01 16.197 0 9.44±1.11 12.43±1.78 9.977 0.000
t   0.861 13.185     0.805 15.247    
P   0.392 0.000     0.423 0.000    
表5  2组BADS评分比较  (x±s,分)
Table 5  Comparison of 2 groups of BADS scores  (x±s,score)
组别 n 干预前 干预3个月后 t P
研究组 49 7.59±1.02 16.31±1.72 30.525 0
对照组 49 7.78±0.96 12.44±1.38 19.404 0
t   0.95 12.285    
P   0.345 0    
  
3  讨论
        缺血性脑卒中患者因脑组织损伤可间接或直接影响相关神经递质与其受体改变,如促皮质激素释放激素、P物质、神经肽、5-HT及谷氨酸等,且脑卒中所致躯体功能障碍、家庭或社会地位改变等也可在一定程度上引发负性情绪,致使其抵触康复训练,不利于机体功能恢复[11-14]。因此,如何对缺血性脑卒中恢复期患者予以有效干预仍是研究热点。
        缺血性脑卒中康复机制在于中枢神经系统功能及结构上具备可塑性和重组能力,主要指神经系统具备适应环境改变的能力,可于功能及结构上发生变化,形成新通路完成学习过程。传统院外康复措施主要集中于自我康复训练、药物控制、改变不良生活方式等,但由于其缺乏对应康复设施及康复技能,导致其实际应用存在局限性[15-17]。而作业疗法主要是基于脑部具有可塑性的理论基础,通过重复训练基本日常生活活动能力,于病灶周边形成新神经通路,从而有效发挥中枢神经代偿作用及重组产生,持续对大脑皮质功能进行重组,以此形成肢体自高级中枢控制的运动模式[18-19]。本研究于实施作业疗法时注重结合患者具体情况,选取实际生活所需应用的作业训练措施,包括个人卫生、基本交流、洗澡、更衣、饮食、轮椅移动等,并对功能改善方面鼓励、引导患者进行阅读、参加社交活动、户外行走、家务等,以此促使其对社会适应能力逐渐恢复,对缓解患者负性情绪状态也具有一定积极意义。但本研究结果发现,干预3个月后研究组MMSE及FMA评分等改善效果与临床预期仍存在一定差距。
        rTMS是近年来发展起来的一种无痛、非侵入性的新型技术,可用于改善大脑皮层功能,其所应用的磁信号可无衰减穿透颅骨对脑神经产生刺激性作用,大脑实质内会在磁场作用下产生感应电流,从而对脑神经元产生刺激,并可根据工作参数不同,大脑或暂时抑制或暂时兴奋,可作为辅助康复干预的方法促进脑的可塑性[20-22]。研究指出,rTMS可通过脉冲磁场直接作用于大脑单侧某一特定的皮质部位,利用感应电流对脑细胞动作电位产生调节作用,并引发远处或皮质局部神经元兴奋性变化,诱导神经网络重构,从而对神经祖细胞及神经干细胞分化及增殖产生刺激性作用,并可通过轴突间作用使其远端也同样可以产生治疗作用,可有效改善和调节脑功能[23-26]。此外,低频rTMS可对大脑皮质兴奋性产生一定调节作用,从而增加边缘系统及纹状体多巴胺生成量,增加乙酰胆碱类神经递质、5-羟色胺及去甲肾上腺素表达水平,扩张脑血管并增大脑局部血流量。同时,低频rTMS可对区域脑血流和新陈代谢产生一定影响,于缺血状态下向脑组织提供长时程保护,可持续到刺激停止后1个月。以此减少患者的神经功能缺损,且能对脑部神经递质表达予以调节,以此有效改善临床症状[27-28]。本研究显示,干预3个月后研究组MMSE、BADS及FMA评分高于对照组,MEP及CMCT改善幅度较对照组更加显著(P<0.05),表明于作业疗法基础上应用低频rTMS,可更有效恢复缺血性脑卒中恢复期患者认知功能及肢体运动功能,改善其执行能力。主要原因:rTMS可导致局部灰质血流计量依赖性改变及皮质代谢改变,并推测rTMS可于缺血性脑卒中临床治疗中改变脑组织区域血流量,进而改善神经可塑性蛋白质代谢,对神经组织产生保护作用,调整脑神经递质分布,恢复神经功能[29-30]。另有研究指出,低频rTMS可促进额叶皮质下白质修复及生长,并能提高脑内三磷酸腺苷水平,改善脑代谢状态,对记忆功能及认知功能等恢复均具有重要作用[31-33]
        此外,缺血性脑卒中病情进展及神经功能与NGF及BDNF表达水平异常关系密切,因此本研究尝试对缺血性脑卒中恢复期患者经作业疗法及低频rTMS干预后上述指标水平变化情况进行探究分析,结果发现干预后研究组血清NGF及BDNF水平高于对照组(P<0.05)。NGF及BDNF均为机体中重要神经营养蛋白物质,在海马和皮质中分布极为广泛,可对神经元予以保护,并促进突触再生,减轻外源性及内源性损伤因素对神经元产生的损害程度[34-37]。研究指出,NGF及BDNF还可为多巴胺神经元、NE神经元及5-HT神经元提供营养及支持,促进神经递质合成,而缺血性脑卒中发病后,可致使神经细胞大量坏死、NGF及BDNF合成量减少,NGF与BDNF含量不足可致使神经细胞所受保护进一步削弱,并导致神经系统处于神经细胞因子含量减少及神经元受损这一恶性循环状态中[38-41]。因此上述结果可证实,作业疗法及低频rTMS联合干预方案还可有效提升缺血性脑卒中恢复期患者血清神经细胞因子含量,对恢复认知功能具有重要意义[42-53],但其具体作用机制仍需进一步探究证实。
        作业疗法联合低频rTMS对缺血性脑卒中恢复期患者实施干预,可增加血清神经细胞因子含量,利于改善其认知功能与肢体运动功能,并提升其执行能力。
 
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(收稿2019-01-25)
本文责编:张喜民

本文引用信息:孔培培,陈颖,翟清华,许梦雅,铁新琴,王静.低频rTMS联合作业疗法在缺血性脑卒中恢复期中的应用[J].中国实用神经疾病杂志,201922(3)238-245.DOI10.12083/SYSJ.2019.03.047 

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