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围产期卒中患儿经颅直流电刺激后光谱生物标志物的变化。

Changes in spectroscopic biomarkers after transcranial direct current stimulation in children with perinatal stroke.

作者信息

Carlson Helen L, Ciechanski Patrick, Harris Ashley D, MacMaster Frank P, Kirton Adam

机构信息

Calgary Pediatric Stroke Program, Alberta Children's Hospital, Calgary, AB, Canada; Alberta Children's Hospital Research Institute (ACHRI), Calgary, AB, Canada; Neurosciences, Alberta Children's Hospital, Calgary, AB, Canada; Department of Pediatrics, University of Calgary, Calgary, AB, Canada.

Calgary Pediatric Stroke Program, Alberta Children's Hospital, Calgary, AB, Canada; Alberta Children's Hospital Research Institute (ACHRI), Calgary, AB, Canada.

出版信息

Brain Stimul. 2018 Jan-Feb;11(1):94-103. doi: 10.1016/j.brs.2017.09.007. Epub 2017 Sep 13.

DOI:10.1016/j.brs.2017.09.007
PMID:28958737
Abstract

BACKGROUND

Perinatal stroke causes lifelong motor disability, affecting independence and quality of life. Non-invasive neuromodulation interventions such as transcranial direct current stimulation (tDCS) combined with intensive therapy may improve motor function in adult stroke hemiparesis but is under-explored in children. Measuring cortical metabolites with proton magnetic resonance spectroscopy (MRS) can inform cortical neurobiology in perinatal stroke but how these change with neuromodulation is yet to be explored.

METHODS

A double-blind, sham-controlled, randomized clinical trial tested whether tDCS could enhance intensive motor learning therapy in hemiparetic children. Ten days of customized, goal-directed therapy was paired with cathodal tDCS over contralesional primary motor cortex (M1, 20 min, 1.0 mA, 0.04 mA/cm) or sham. Motor outcomes were assessed using validated measures. Neuronal metabolites in both M1s were measured before and after intervention using fMRI-guided short-echo 3T MRS.

RESULTS

Fifteen children [age(range) = 12.1(6.6-18.3) years] were studied. Motor performance improved in both groups and tDCS was associated with greater goal achievement. After cathodal tDCS, the non-lesioned M1 showed decreases in glutamate/glutamine and creatine while no metabolite changes occurred with sham tDCS. Lesioned M1 metabolite concentrations did not change post-intervention. Baseline function was highly correlated with lesioned M1 metabolite concentrations (N-acetyl-aspartate, choline, creatine, glutamate/glutamine). These correlations consistently increased in strength following intervention. Metabolite changes were not correlated with motor function change. Baseline lesioned M1 creatine and choline levels were associated with clinical response.

CONCLUSIONS

MRS metabolite levels and changes may reflect mechanisms of tDCS-related M1 plasticity and response biomarkers in hemiparetic children with perinatal stroke undergoing intensive neurorehabilitation.

摘要

背景

围产期卒中会导致终身运动功能障碍,影响独立性和生活质量。非侵入性神经调节干预措施,如经颅直流电刺激(tDCS)联合强化治疗,可能会改善成人卒中偏瘫患者的运动功能,但在儿童中尚未得到充分研究。用质子磁共振波谱(MRS)测量皮质代谢物可以了解围产期卒中的皮质神经生物学情况,但这些代谢物如何随神经调节而变化尚待探索。

方法

一项双盲、假刺激对照、随机临床试验测试了tDCS是否能增强偏瘫儿童的强化运动学习疗法。为期10天的定制化、目标导向疗法与对侧初级运动皮层(M1区,20分钟,1.0毫安,0.04毫安/平方厘米)的阴极tDCS或假刺激配对。使用经过验证的测量方法评估运动结果。在干预前后,使用功能磁共振成像引导的短回波3T MRS测量双侧M1区的神经元代谢物。

结果

研究了15名儿童[年龄(范围)=12.1(6.6 - 18.3)岁]。两组的运动表现均有改善,且tDCS与更高的目标达成率相关。阴极tDCS后,未受损的M1区谷氨酸/谷氨酰胺和肌酸减少,而假刺激tDCS后代谢物无变化。受损M1区的代谢物浓度在干预后未改变。基线功能与受损M1区代谢物浓度(N - 乙酰天门冬氨酸、胆碱、肌酸、谷氨酸/谷氨酰胺)高度相关。干预后这些相关性的强度持续增加。代谢物变化与运动功能变化无关。基线时受损M1区的肌酸和胆碱水平与临床反应相关。

结论

MRS代谢物水平及其变化可能反映了在接受强化神经康复治疗的围产期卒中偏瘫儿童中,与tDCS相关的M1可塑性机制及反应生物标志物。

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