肌电图评价肌萎缩侧索硬化389例嗅鞘细胞脑内移植的效果

Electromyogram evaluation in 389 patients with amyotrophic lateral sclerosis following olfactory ensheathing cell intracranial transplantation

背景：肌萎缩侧索硬化尚缺乏有效治疗手段，细胞学治疗是研究的重要方向之一。目前研究表明，嗅鞘细胞、骨髓基质细胞、脐血间质干细胞等具有一定临床疗效。目的：观察嗅鞘细胞脑内移植治疗肌萎缩侧索硬化的肌电图改变，分析肌电图检查对肌萎缩侧索硬化疗效的评定价值。设计、时间及地点：病例自身对照观察，于2003-09／2007—12在北京市虹天济神经科学研究院及北京康复中心神经外科完成。对象：选择389例接受胚胎嗅鞘细胞脑内移植治疗的肌萎缩侧索硬化患者。方法：局麻下作双额发际内2．0～3．0cm，旁开中线2．5～2．9cm，长约0．5cm小切口2个，两侧共缓慢注射细胞数2×10^4／μL嗅鞘细胞悬液100μL。移植前及移植后三四周分别采用丹麦Keypoint-4型肌电／诱发电位仪检查患者肌电图。主要观察指标：每例患者检查8～12块肌肉，包括四肢近、远端肌肉以及舌肌、胸锁乳突肌。移植前后肌电图主要列比自发电位、运动单位电位以及大力收缩时募集波型的改变。结果：①389例患者中332例（853％）肌电图检查显示不同程度改善，主要有3类：a．自发电位减少：122例出现不同程度此项改变。b．300例出现数量不等的肌肉募集波型由低级向高级转变，电位密度明显增加，如单纯相转变为混合相；混合相转变为干扰相。c．移植前未能测到运动单位电位而术后新出现者51例。②51例（13．2％）肌电图无变化，移植前后肌电图大致相同。③6例（1．5％）比移植前差，主要变化为自发电位增多或肌肉大力收缩时募集波型减弱。结论：嗅鞘细胞移植近期能改善肌萎缩侧索硬化患者的神经功能，延缓病情的进行性恶化。肌电图检测用于胚胎嗅鞘细胞移植治疗肌萎缩侧索硬化疗效评定具有较好的应用价值，通过移植前后肌电图改变可以较客观反映治疗的有效性。

BACKGROUND： Amyotrophic lateral sclerosis lacks of effective therapeutic method. Cytology therapy is one of research direction. Several studies have revealed that the management of olfactory ensheathing cells, bone marrow stromal cells, umbilical cord blood mesenchymal stem cells have obtained good clinical outcomes. OBJECTIVE： To observe electromyogram changes in olfactory ensheathing cell grafting for amyotrophic lateral sclerosis, and to analyze evaluation of electromyographic examination on outcome of amyotrophic lateral sclerosis. DESIGN, TIME AND SETTING： The self-controlled observation was conducted at the Beijing Hongtianji Neuroscience Academy and Department of Neurosurgery of Beijing Rehabilitation Center between September 2003 and December 2007. PARTICIPANTS： 389 amyotrophic lateral sclerosis participants were enrolled in this clinical study for fetal olfactory ensheathing cell transplantation. METHODS： After local anesthesia, two about 0.5-cm incisions were made 2.0-3.0 cm in bilateral frontal hairline, 2.5-2.9 cm lateral to midline. 2×10^4/μL olfactory ensheathing cell suspension （100 μL） was slowly injected into the bilateral regions. Electromyogram examination was performed Keypoint-4 electromyograph of evoked potential before and 3 to 4 weeks after fetal olfactory ensheathing cell transplantation. MAIN OUTCOME MEASURES： Eight to twelve muscles were tested, which included proximal and distal part of four limbs, muscles of tongue, and sternocleidomastoideus muscle. The amount of spontaneous potential, motor unit potential and wave pattern were recorded during maximal voluntary contraction of tested muscle in electromyography. RESULTS： Among 389 patients, improvement of electromyogram results were displayed in 332 （85.3%）, including ①Spontaneous potentials diminished in 122 patients; ②Recruitment pattern of the maximal voluntary contraction of involved muscles improved which became more intensive and partially together with increased number of motor unit potential in 300 patients; ③Motor unit potential recorded successfully which failed to occur before surgery in 51 patients. No remarkable changes in electromyogram were observed in 51 patients （13.2%）, and electromyogram became worsen in 6 （1.5%） compared with that before surgery. Main changes were increase in spontaneous potential or decrease in recruiting wave during maximal voluntary contraction of tested muscle. CONCLUSION： Olfactory ensheathing cell transplantation can improve nerve function in amyotrophic lateral sclerosis patients, and delay progressive aggravation of patients＇ condition. Electromyogram examination has a good application value in assessing outcome of olfactory ensheathing cell transplantation for treating amyotrophic lateral sclerosis. Electromyogram changes can objectively reflect therapeutic effectiveness.