臺灣博碩士論文加值系統

背景及目的：經顱直流電刺激（transcranial direct current stimulation, tDCS）雙側運動皮質（primary motor cortices, M1）較單側皮質刺激被認為更能提昇健康受試者的運動反應和皮質脊髓興奮性。中風後，從非損傷腦側M1到損傷側M1的腦半球間抑制性會異常升高，影響中風患者的功能恢復，然而，亞急性中風患者復健中結合雙側tDCS是否可能影響雙側M1的皮質興奮性仍然未知，我們的研究目的在探討亞急性中風患者在復健中施予雙側運動皮質tDCS的安全性和有效性。
方法：我們收錄12位第一次單側皮質下缺血性中風的亞急性病患（中風後2-4週）和13位條件相符的健康對照組進行了隨機交叉假刺激對照研究。在執行偏癱或非優勢橈側伸腕肌群運動時，受試者在分開的兩天接受真或假tDCS。真刺激tDCS是將陽極電片放置在損傷腦同側或非優勢M1上，而陰極電片放置在非損傷腦側或優勢M1上; 2毫安培20分鐘；假刺激tDCS則是電片放置相同的位置，但電刺激只有前2分鐘。我們在刺激前評估美國國衛院腦中風評估表（National Institutes of Health Stroke Scale, NIHSS）、Modified Rankin Scale（mRS）、Fugl-Meyer Assessment-Upper Extremity（FMA-UE）和Action Research Arm Test（ARAT），在刺激前後使用經顱磁刺激比較運動誘發電位（motor evoked potentials, MEPs）、大腦半球間抑制性的同側靜止期（ipsilateral silent period, iSP）和短間隔腦皮質內抑制（short interval intracortical inhibition, SICI）的變化。
結果：相較於假刺激，健康對照組在真刺激後顯著增加陽極刺激側M1的MEPs、減少SICI、並且延長iSP增加對側抑制，而在陰極刺激的M1減少MEPs、並且縮短iSP減少對側抑制，效果至少持續30分鐘。在中風患者也有相似的結果，真刺激後陽極損傷側M1增加MEPs、減少SICI、並且延長iSP增加對側抑制，同時陰極刺激非損傷側M1減少MEPs、增加SICI、並縮短iSP減少對側抑制。有趣的是，在中風患者控制了年齡、基準NIHSS、FMA-UE和MEP%變因之後，我們發現基準iSP的雙側比值有意義地預測真假刺激後陽極損傷側MEPs的變化差異量並呈現負相關（P= 0.04），且刺激沒有發生明顯副作用。
結論：亞急性中風患者復健中施予雙側tDCS可以安全並同步調節雙側M1興奮性和大腦半球間的抑制性，大腦半球間的抑制性的基準比值可能預測亞急性中風病患接受雙側M1 tDCS的反應程度。（臺北榮總人體試驗許可編號：2014-01-006C；美國臨床試驗註冊序號：NCT02158312）

Background and objective: Dual transcranial direct current stimulation (tDCS) to bilateral primary motor cortices (M1) has been suggested to enhance motor reaction and corticospinal excitability compared with unilateral tDCS in healthy subjects. After stroke, the contralesional hyperexcitatory M1 may impede functional recovery of the paretic hand through transcallosal inhibition of ipsilesional M1. It remains unknown how dual tDCS in combination with rehabilitation may affect motor cortical excitability and transcallosal intercations bilaterally in subacute stroke patients. Here we examined safety and efficacy of task-concurrent dual tDCS over the M1 in subacute stroke patients.
Methods: We conducted a randomized, single-blind crossover sham-controlled study in 12 subacute (2-4 weeks after onset) stroke patients with first-time, unilateral, subcortical ischemic stroke and 13 matched healthy controls. During exercising the paretic or non-dominant extensor carpi radialis, participants underwent two different tDCS conditions on separate days, i.e. real tDCS (anode over the ipsilesional or non-dominant M1, while cathode over the contralesional or dominant M1; 2 mA for 20 mins) and sham tDCS (same settings except for initial 2 mins). We evaluated the National Institutes of Health Stroke Scale (NIHSS), Modified Rankin Scale (mRS), Fugl-Meyer Assessment- Upper Extremity (FMA-UE) and Action Research Arm Test (ARAT) of patients and compared the changes of motor evoked potentials (MEPs), ipsilateral silent period (iSP) for interhemispheric inhibition and short interval intracortical inhibition (SICI) in all participants using transcranial magnetic stimulation before and after tDCS.
Results: Compared with sham stimulation, the real tDCS significantly increased MEPs, reduced SICI, and prolonged iSP of the anode-stimulated non-dominant M1, while decreased MEPs and shortened iSP of the cathode-stimulated dominant M1 in healthy controls for at least 30 mins. Similarly in stroke patients, the real tDCS increased MEPs, reduced SICI, and prolonged iSP of the anode-stimulated ipsilesional M1, while decreased MEPs, increased SICI, and shorten iSP of the cathode-stimulated contralesional M1. Interestingly, after adjustments of age, NIHSS, FMA-UE and baseline MEPs, we found that the baseline iSP ratio significantly predicted the MEP changes after tDCS in a negative correlation fashion. No adverse effects were observed.
Conclusions: Task-concurrent dual tDCS can safely and synchronously modulate bilateral M1 excitability and interhemispheric inhibition in subacute stroke patients. Their baseline interhemispheric inhibition ratio could be used to predict the dual tDCS responders and responses. Taipei Veterans General Hospital IRB No.: 2014-01-006C; ClinicalTrials.gov: NCT02158312.

誌謝 I
中文摘要 III
英文摘要 IV
目錄 V
縮寫中英對照 VII
第一章 背景 1
第一節 中風後復健的時機：急性、亞急性到慢性期的實証 1
第二節 非侵襲性經顱腦刺激和中風後的神經可塑性 2
第三節 比較單側與雙側經顱直流電刺激健康人運動皮質的效應 6
第四節 雙腦經顱直流電刺激中風後運動皮質的安全性和療效？ 7
第二章 目的 10
第三章 方法 11
第一節 受試者條件 11
第二節 實驗設計 11
第三節 經顱直流電刺激及安全評估 11
第四節 神經功能和動作功能評估 12
第五節 經顱磁刺激評估 12
第六節 腦磁振造影 13
第七節 統計分析 13
第四章 結果 15
第一節 亞急性中風病患的特徵和腦梗塞位置 15
第二節 亞急性中風病患和健康人運動皮質的電生理基準值差異和經顱直流電刺激安全性 15
第三節 亞急性中風病患和健康人接受經顱直流電刺激後電生理改變 16
第四節 亞急性中風病患和健康對照者對經顱直流電刺激的反應比例 17
第五節 預測經顱直流電刺激可改變運動皮質興奮性的因子 18
第五章 結論 19
第六章 討論 20
第一節 本研究的主要新穎發現 20
第二節 本研究與過往文獻的異同之處 20
第三節 本研究的限制與未來研究方向 22
參考文獻 23
附圖 35
圖1 收案流程及受試者納入和排除條件 35
圖2 實驗設計 36
圖3 亞急性中風病患的腦梗塞位置 37
圖4 經顱直流電刺激後中風病患和健康對照者的運動皮質興奮性的改變 38
圖5 亞急性中風病患和健康對照者對經顱直流電刺激的反應比例 40
圖6 經顱直流電刺激運動皮質興奮性改變的預測因子 41
圖7 雙腦經顱直流電刺激效應的理論機制圖 42
附表 43
表1 文獻回顧單次雙腦經顱直流電刺激運動皮質的研究 43
表2 文獻回顧多次雙腦經顱直流電刺激中風後運動皮質的研究 48
表3 亞急性中風病患的基本特徵 51
表4 亞急性中風病患和健康對照者運動皮質的電生理基準值比較 52

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