中风后痉挛的治疗及影像学研究进展

作者:未知

   【摘要】 中风后痉挛(post-stroke spasticity,PSS)是脑卒中患者常见功能障碍,严重影响患者的恢复,是临床脑卒中康复治疗的难点。目前临床上传统治疗效果差,根本原因是对痉挛发生的中枢机制并不明确。本文介绍了国内外有关重复经颅磁刺激(research on repetitive transcranial magnetic stimulation,rTMS)治疗痉挛的最新研究和痉挛中枢机制的研究进展。
   【关键词】 痉挛; 中风; 重复经颅磁刺激; 磁共振
   doi:10.14033/j.cnki.cfmr.2019.19.083 文献标识码 A 文章编号 1674-6805(2019)19-0-04
   Research Progress in Treatment and Imaging of Post-stroke Spasticity/YUAN Mengzhe,JIANG Wei,ZHAO Xin,et al.//Chinese and Foreign Medical Research,2019,17(19):-188
   【Abstract】 Post-stroke spasticity(PSS) is a common dysfunction in stroke patients which seriously affects the recovery of patients,and is a difficult point in clinical stroke rehabilitation.At present,traditional treatment is poorly effective,the underlying reason is that the central mechanism of spasticity is not clear.This paper introduces the latest research on repetitive transcranial magnetic stimulation(rTMS) treatment of spasticity at home and abroad and the research progress of spasticity central mechanism.
   【Key words】 Spasticity; Stroke; Repetitive transcranial magnetic stimulation; Magnetic resonance imaging
   First-author’s address:Jiangsu Province Rongjun Hospital,Wuxi 214035,China
   中風后痉挛(post-stroke spasticity,PSS)是脑卒中患者常见功能障碍,发生率高达20%~46%,对患者的康复造成严重影响[1-2]。目前痉挛的定义尚未统一,1980年Lance[3]提出定义:痉挛是一种以速度依赖为特征的紧张性牵张反射增强,并伴腱反射亢进,是上运动神经元损伤的表现之一。2005年Pandyan等[4]对痉挛提出了新的定义:痉挛是由于上运动神经元损伤所致的一种感觉运动控制障碍,表现为间断或持续的肌肉不自主运动。现阶段国内外最常用的方法是传统物理疗法结合局部肌肉注射A型肉毒毒素治疗痉挛,但注射治疗具有明显的副作用且时效性短,而传统物理治疗效果较差[5]。以上治疗均不能取得较好的临床效果,根本原因是对痉挛发生的中枢机制不明确。因此,探索有效减轻脑卒中后痉挛的方法及痉挛的中枢机制,对于改善患者的预后和生活质量,减轻家庭和社会负担,具有极为重要的经济和社会意义。
  1 痉挛的治疗
   经颅磁刺激(transcranial magnetic stimulation,TMS)被誉为二十一世纪四大脑科学技术之一,由Barker等[6]在1985年首次提出。TMS是一种利用一定强度的时变磁场在脑内诱发感应电流,调节脑内代谢和神经电生理活动的技术,具有无痛、无创、非侵入性等优势。重复经颅磁刺激(repetitive transcranial magnetic stimulation,rTMS)是在TMS基础上发展起来的新的神经电生理技术,对于中风患者来讲,rTMS对皮质活动的影响比TMS更强[7-8]。rTMS最大刺激深度达到6 cm,因此可以刺激到大脑深部神经元,从而改变大脑皮质的兴奋性以达到治疗痉挛的目的[9-10]。
   目前rTMS已被广泛应用于神经系统疾病的治疗,但有关rTMS治疗脑卒中后上肢痉挛的报道较少,且多为临床效果研究。有研究中采用1 Hz低频rTMS刺激卒中患者健侧半球4周后,发现与单纯康复治疗相比,1 Hz rTMS可更有效缓解痉挛[11]。Málly等[12]发现对传统康复治疗效果不明显的多年中风患者使用rTMS,依然可以改善肢体运动和痉挛情况。Kakuda等[13]将作业疗法与rTMS结合,对15例卒中后上肢痉挛的患者进行15 d
  干预,发现治疗后患者的改良Ashworth、FMA评分、WMF测试均有改善,证实低频rTMS联用作业疗法对中风后上肢功能障碍伴痉挛的患者有效。Yamada等[14]将rTMS、局部注射肉毒杆菌毒素和作业疗法联合应用,发现该三联疗法对中风后上肢痉挛患者有明显疗效。Naghdi等[15]对下肢痉挛患者下肢运动皮质区进行rTMS治疗,1周后患者MAS、FMA、起立行走测试和H反射、MEP等神经电生理评估均有提高,表明患者下肢痉挛程度明显改善。Du等[16]用3 Hz、1 Hz rTMS和假rTMS对脑卒中后运动功能障碍患者进行5 d的治疗,结果显示rTMS组比假rTMS组运动功能改善更显著。Pundik等[17]研究表明,23例卒中后痉挛患者运动功能评分(Fugl-Meyer评分)和上肢痉挛评分(MAS评分)具有线性相关关系,提示应用运动相关量表作为评价痉挛的指标具有参考意义。   2 痉挛的中枢机制
   卒中后痉挛(post-strokespasticity,PSS)是脑卒中患者常见并发症,发生机制十分复杂。其中半球间竞争模型认为,健康人双侧半球之间存在相互抑制和竞争以保持平衡,而这种平衡在卒中后被打破,从而导致痉挛[18]。近年来有学者提出“双向平衡”恢复模型(Bimodal balance-recovery model),该模型将半球间平衡与结构保留完整度(如运动区、皮质脊髓束)联系起来,由结构保留完整度的高低决定了神经调控的策略[19]。随着磁共振成像技术的发展,为进一步探索中风后痉挛的发生机制提供了影像学支持。
  2.1 中风后运动功能障碍的影像学研究
   VBM和DTI可显示脑梗死后的结构改变。VBM是一种基于体素的形态学测量方法,可以定量检测出脑灰质、白质密度及体积的变化,从而显示常规MRI检查无法显示的脑组织结构改变[20]。Gauthier等[21]将慢性卒中患者分为强制运动疗法组和常规对照组,结果发现强制性运动组双侧大脑感觉运动区和海马的灰质大量增加,且增加幅度与运动功能改善显著相关。Kraemer等[22]对10例大脑中动脉区域首次卒中患者进行回顾性分析发现,中风后不仅靠近病灶的脑区存在损伤,远离的脑区也存在损伤。Fan等[23]将10例卒中患者和健康人对比,发现健侧半球与认知相关脑区(例如海马及楔前叶)出现体积增加,这些区域的有效代偿促进了患者功能的恢复。蔡建新等[24]利用VBM研究方法发现,皮层下脑卒中后存在广泛的远隔皮层重塑并可能与患者的功能预后相关,这与Gauthier等[25]研究结果相符。Yin等[26]运用VBM和基于纤维束示踪的空间统计方法(TBSS)研究FA值的变化与运动功能改善之间的关系,VBM和TBSS揭示了相似的结果。
   fMRI包括任务态和静息态,可以直观地观察中风后痉挛的脑功能改变。Du等[27]通过10 Hz、1 Hz rTMS和假rTMS对首发卒中患者进行连续5 d的干预,结果表明,rTMS组运动改善情况显著优于假rTMS组;任务态fMRI结果显示,HF-rTMS组患侧运动区皮层兴奋性显著增加,而LF-rTMS组显示健侧运动区皮层兴奋性显著降低。静息态fMRI不需要接受任务可避免人为因素影响,尤其适合于主动配合性差的患者[28]。Park等[29]对12例卒中患者进行发病后1、3、6个月的静息态fMRI研究,与健康受试者对比发现患侧M1区与同侧额叶、顶叶皮层、双侧丘脑及小脑的连接增强,与对侧M1区和枕叶皮质的连接减弱。发病6个月后,患侧M1区与对侧丘脑、辅助运动区和额中回的功能连接强度与运动恢复呈正相关。Yin等[30]研究慢性皮层下梗死患者24例,分为完全瘫痪组12例和部分瘫痪组
  12例,与健康对照组相比,部分瘫痪组中患侧半球的Reho增加,而完全瘫痪组则是健侧半球的Reho增加;此外,还检查到与部分瘫痪组相比,完全瘫痪组中的健侧半球前运动皮质和患侧半球内侧额回ReHo值增加。
  2.2 痉挛的影像学研究
   目前国内外有关rTMS治疗卒中后痉挛的研究报道多为临床效果研究,基于神经影像学的相关机制尚不明确,且多为基于任务态fMRI的分析研究。Bergfeldt等[31]对6例首次卒中患者(均右侧痉挛)注射A型肉毒毒素,发现6例患者中5例痉挛明显改善,治疗前与健康受试者对比,患者右侧大脑表现出明显的活动增强,治疗后右侧半球活动明显下降,双侧半球激活趋于正常化。Yamada等[32]研究中,对47名中风后上肢运动功能障碍患者进行1 Hz的rTMS治疗,根据功能磁共振检查结果将患者分为双侧半球激活和单侧半球激活两组,两组的运动功能均显著改善,其中双侧半球激活组M1区偏侧化指数显著增加,表明活化体素向损伤半球转变,而单侧半球激活组表现出损伤半球的激活显著增加,表明rTMS可以诱导皮层功能重组,从而改善运动功能。Veverka等[33]的研究结果表明,用肉毒毒素治疗PSS(中风后痉挛)患者可使经典运动系统外的脑结构激活减少,调节皮层重组使运动网络正常化,这种调节可能是运动功能改善的主要机制。
   Cheung等[34]对97例卒中患者进行研究,分为46例非痉挛组和51例痉挛组,通过CT和磁共振图像追踪病灶,并将图像配准到对称的脑模板,从痉挛组中减去非痉挛组的覆盖图以确定在痉挛患者中更普遍损害的脑区。将痉挛组按上肢(肘部或腕部)改良Ashworth(MAS)评分,从1级(轻度)至3级(严重)分四组,每组7人进行类似的分析(减法分析和Fisher精确检验)后,最终壳核被确定为痉挛个体中最常发生损伤的区域。本研究建立了卒中后痉挛状态的神经解剖学关联,并陈述了混合脑成像模式(包括计算机断层扫描成像)与病变特征和痉挛严重程度之间的关系。痉挛的严重程度与脑损伤的部位相关,且病变的体积和痉挛的程度呈正相关。基于核磁共振成像技术定位痉挛相关脑区显示:在壳核、内囊(后肢)、岛叶及丘脑区域中的病灶密度较大。在比较脑卒中患者痉挛的病灶重叠程度时,发现壳核可作为划分有无痉挛的区域,暗示了壳核是“痉挛”区域,而不仅仅是共同的脑卒中损伤的位置[35]。这些锥体外系的结构完整性已被确定为卒中后发生痉挛的关键决定因素,但是關于痉挛状态和壳核病变的直接证据仍然不足,然而,这些病变位置对痉挛发展的影响可能是通过间接的路线发生的。除了壳核以外的其他脑区的病变也被认为与痉挛有关,内囊(后肢)、岛叶、基底节及丘脑区域也存在广泛重叠。有研究表明,内囊后肢占位性病变与运动障碍的严重程度存在关联,此外,内囊后肢和背侧丘脑的损伤也与功能恢复有关,证实了包括皮质、丘脑和脑桥核团之间连接的神经纤维及作为运动控制所必需的解剖结构的完整性都与痉挛有着直接或间接的联系[36]。
  3 不足与展望
   由于临床上痉挛病例收集较为困难,且受到发病部位、病程、年龄等各种因素的影响,因此,至今还没有明确与痉挛相关的特定脑区。目前与痉挛相关的研究多基于任务态,受到患者主观认知的影响较大。为此,研究中需要严格把控入选标准,纳入病变部位、病程一致性高的病例,且需要开展大样本、高质量、分阶段长期跟踪的试验。其次,科研设计要更加严瑾,将误差降到最低。最后,尝试不同的影像学分析方法从多角度分析痉挛。   參考文献
  [1] Opheim A,Danielsson A,Alt M M,et al.Upper-limb spasticity during  the first year after stroke:stroke arm longitudinal study at the University of Gothenburg[J].American Journal of Physical Medicine & Rehabilitation,2014,93(10):884-896.
  [2] Wissel J,Manack A,Brainin M.Toward an epidemiology of poststroke spasticity[J].Neurology,2013,80(3 Suppl 2):S13-S19.
  [3] Lance J W.Pathophysiology of spasticity and clinical experience with Baclofen.Spasticity:disorderd motor control[M].Chicago:Year Book Medical Publishers,1980:185-203.
  [4] Pandyan A D,Gregoric M,Barnes M P,et al.Spasticity clinical perceptions neurological realities and meaningful measurement[J].Disabil Rehabil,2005,27(2):2-6.
  [5] Alessandro P,Francesca D,Manoj B.Efficacy of therapeutic ultrasound and transcutaneous electrical nerve stimulation compared with botulinum toxin type A in the treatment of spastic equinus in adults with chronic stroke:a pilot randomized controlled trial[J].Top Stroke Rehabil,2014,21(Suppl 1):S8-S16.
  [6] Barker A T,Jalinous R,Freeston I L.Noninvasive magnetic stimulation of the human motor cortex[J].Lancet,1985,325(8437):1106-1107.
  [7] Hummel F C,Cohen L G.Non-invasive brain stimulation:a new strategy to improve neurorehabilitation after stroke?[J].Lancet Neurol,2006,5(8):708-712.
  [8]翁春晓,范肖冬,侯冰.经颅刺激对脑功能的调节作用[J].生物医学工程与临床,2015,19(2):196-200.
  [9] Sasaki N,Kakuda W,Abo M.Bilateral high-and low-frequency rTMS in acute stroke patients with hemiparesis:a comparative study with unilateral high-frequency rTMS[J].Brain Injury,2014,28(13-14):1682-1686.
  [10] Kakuda W,Abo M,Kobayashi K,et al.Anti-spastic effect of low-frequency rTMS applied with occupational therapy in post-stroke patients with upper limb hemiparesis[J].Brain Injury,2011,25(5):496-502.
  [11] Galv?o S C B,Santos R B C D,Santos P B D,et al.Efficacy of coupling repetitive transcranial magnetic stimulation and physical therapy to reduce upper-limb spasticity in patients with stroke:a randomized controlled trial[J].Archives of Physical Medicine & Rehabilitation,2014,95(2):222-229.
  [12] Málly J,Dinya E.Recovery of motor disability and spasticity in post-stroke after repetitive transcranial magnetic stimulation(rTMS)[J].Brain Research Bulletin,2008,76(4):388.
  [13] Kakuda W,Abo M,Kobayashi K,et al.Low-frequency repetitive transcranial magnetic stimulation and intensive occupational therapy for poststroke patients with upper limb hemiparesis:preliminary study of a 15-day protocol[J].International Journal of Rehabilitation Research,2010,33(4):339-345.   [14] Yamada N,Kakuda W,Kondo T,et al.Local muscle injection of botulinum toxin type A synergistically improves the beneficial effects of repetitive transcranial magnetic stimulation and intensive occupational therapy in post-stroke patients with spasticcupper limb hemiparesis[J].European Neurology,2014,72(5-6):290-298.
  [15] Naghdi S,Ansari N N,Rastgoo M,et al.A pilot study on the effects of low frequency repetitive transcranial magnetic stimulation on lower extremity spasticity and motor neuron excitability in patients after stroke[J].J Bodyw Mov Ther,2015,19(4):616-623.
  [16] Du J,TianL,Liu W,et al.Effects of repetitive transcranial magnetic stimulation on motor recovery and motor cortex excitability in patients with stroke:a randomized controlled trial[J].European Journal of Neurology,2016,23(11):1666-1672.
  [17] Pundik S,Falchook A D,Mccabe J,et al.Functional brain correlates of upper limb spasticity and its mitigation following rehabilitation in chronic stroke survivors[J].Stroke Research & Treatment,2014(3):306325.
  [18] Harris-Love M L,Chan E,Dromerick A W,et al.Neural substrates of motor recovery in severely impaired stroke patients with hand paralysis[J].Neurorehabil Neural Repair,2016,30(4):328-338.
  [19] Pino G D,Pellegrino G,Assenza G,et al.Modulation of brain plasticity in stroke:a novel model for neurorehabilitation[J].Nature Reviews Neurology,2014,10(10):597-608.
  [20]張敬,张成周,张云亭.基于体素的形态学测量技术临床应用进展[J].国际医学放射学杂志,2010,33(4):314-317.
  [21] Gauthier L V,Taub E,Perkins C,et al.Remodeling the brain:plastic structural brain changes produced by different motor therapies after stroke[J].Stroke,2008,39(5):1520.
  [22] Kraemer M,Schormann T,Hagemann G,et al.Delayed shrinkage of the brain after ischemic stroke:preliminary observations with voxel-guided morphometry[J].Journal of Neuroimaging,2004,14(3):265-272.
  [23] Fan F M,Zhu C Z,Chen H,et al.Dynamic brain structural changes after left hemisphere subcortical stroke[J].Hum Brain Mapp,2013,34(8):1872-1881.
  [24]蔡建新,冀旗玲,那旭,等.皮层下梗死远隔皮层重塑VBM初步研究[J].临床放射学杂志,2014,33(9):1309-1314.
  [25] Gauthier L V,Taub E,Mark V W,et al.Atrophy of spared gray matter tissue predicts poorer motor recovery and rehabilitation response in chronic stroke[J].Stroke,2012,43(2):453-457.
  [26] Yin D,Yan X,Fan M,et al.Secondary degeneration detected by combining voxel-based morphometry and tract-based spatial statistics in subcortical strokes with different outcomesin hand function[J].American Journal of Neuroradiology,2013,34(7):1341-1347.   [27] Du J,Yang F,Hu J P,et al.Effects of high-and low-frequency repetitive transcranial magnetic stimulation on motor recovery in early stroke patients:evidence from a randomized controlled trial with clinical,neurophysiological and functional imaging assessments[J].NeuroImage Clinical,2019(21):101620.
  [28]周玉梅,孙佳蕾.静息态fMRI技术在临床的应用-局部一致性研究[J].中风与神经疾病杂志,2014,31(4):382-384.
  [29] Park C H,Chang W H,Ohn S H,et al.Longitudinal changes of resting-state functional connectivity during motor recovery after stroke[J].Stroke,2011,42(5):1357-1362.
  [30] Yin D,Luo Y,Song F,et al.Functional reorganization associated with outcome in hand function after stroke revealed by regional homogeneity[J].Neuroradiology,2013,55(6):761-770.
  [31] Bergfeldt U,Jonsson T,Bergfeldt L,et al.Cortical activation changes and improved motor function in stroke patients after focal spasticity therapy-an interventional study applying repeated fMRI[J].BMC Neurol,2015,15(1):1-12.
  [32] Yamada N,Kakuda W,Senoo A,et al.Functional cortical reorganization after low-frequency repetitive transcranial magnetic stimulation plus intensive occupational therapy for upper limb hemiparesis:evaluation by functional magnetic resonance imaging in poststroke patients[J].International Journal of Stroke,2013,8(6):422-429.
  [33] Veverka T,Hlu?tík P,Hok P,et al.Cortical activity modulation by botulinum toxin type A in patients with post-stroke arm spasticity:real and imagined hand movement[J].Journal of the Neurological Sciences,2014,346(1-2):276-283.
  [34] Cheung D K,Climans S A,Black S E,et al.Lesion characteristics of individuals withupper limb spasticity after stroke[J].Neurorehabilitation & Neural Repair,2015,30(1):63.
  [35] Bradnam L V,Stinear C M,Barber P A,et al.Contralesional hemisphere control of the proximal paretic upper limb following stroke[J].Cerebral Cortex,2012,22(11):2662-2671.
  [36] Huynh W,Krishnan A V,Lin C S,et al.Botulinum toxin modulates cortical maladaptation in post-stroke spasticity[J].Muscle & Nerve,2013,48(1):93-99.
  (收稿日期:2019-04-29) (本文編辑:李盈)
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