资金来自运动神经元病研究所澳大利亚（MNDRIA），西尔维亚和查尔斯Viertel慈善基金会临床研究员补助，Ramaciotti基金会和澳洲国家健康与医学研究委员会（项目批准号APP1024915）的支持表示感谢。

1。病人准备<ol><li>前瞻性和连续招术。注:以下协议批准悉尼西区健康服务人类研究伦理委员会。知情同意是由所有患者提供。患者进行前瞻性和连续招募从ALS /神经肌肉诊所在Westmead医院。 </li><li>确定ALS患者进行测试的适用性。排除谁没有被诊断患有ALS或神经肌肉疾病的患者。 </li><li>排除患者有共存的焦点神经病变，神经病变的中位数在手肘处的手腕或尺神经病变。 </li><li>排除患者的一个广义的神经病，如糖尿病性神经病。 </li><li>广泛调查和临床随访患者，以确认ALS或神经肌肉模拟疾病的诊断。 </li><li>确保知情同意后，所有患者提供的，包括ALS和模仿神经肌肉障碍的患者，对人升的神经生理过程。 </li></ol> 2。临床评估<ol><li>通过使用肌萎缩侧索硬化症功能评分量表-修订版（ALSFRS-R）得分18确定所有ALS患者的临床分期。 </li><li>判断疾病进展率在所有ALS患者根据先前报道的公式; 症状（48-ALSFRS-R）/持续时间）19。 </li><li>确定使用医学研究理事会（MRC）评定量表20所有患者的肌肉力量。制定一个总的MRC评分包括上肢（肩外展，屈肘，伸肘，腕关节背伸，手指拐带;拇指外展，总成绩60）和下肢（屈髋，膝关节伸直，踝关节背屈，总分30）的肌肉群。总MRC得分应该是90，如果肌力正常。 </li><li>确定发病的部位，定义为延髓或肢体，在所有的ALS患者。 </li></ol> 3。神经电生理评估<ol><li>承接从绑架者记录正中神经和尺神经与复合肌肉动作电位（CMAP）的反应运动神经传导研究拇短肌（APB），第一骨间背侧（FDI）和外展位数MINIMI（ADM）的肌肉。 </li><li>准备刺激部位在手腕上，通过清洁皮肤表面与磨料凝胶以降低皮肤抵抗力，其次是应用程序中的酒精擦拭。将刺激电流至20％，须出示一个最大的CMAP响应（超强电流）强度以上。 </li><li>确保所选择的刺激部位表现出的刺激，使得容积传导是可以避免的最低门槛。 </li><li>通过清洁皮肤表面与磨料凝胶以降低皮肤抵抗力，其次是应用程序中的酒精擦拭准备录制现场超过每一块肌肉。 </li><li>记录该化合物激活电机的尺寸从建业，ADM，外国直接投资和肌肉电位（CMAP）。回应者定位于在每个肌肉肌腱腹布置10 mm镀金盘电极记录。具体来说，定位活性电极在相应的肌肉，确保负起飞CMAP响应的中点，而被定位在拇指（APB和外国直接投资CMAP录音），数字5的基础的基础参比电极（为ADM CMAP录音）。 </li><li>设定刺激阴极和活性电极为APB和ADM化合物马达动作〜5厘米和8厘米的距离的FDI潜在反应之间的距离。 </li><li>定位在电中性接地导板放在手的背侧，刺激和G1电极，具有导电性的凝胶，以减少伪像之间。通过清洁皮肤表面与磨料凝胶，以减少皮肤电阻，随后应用的醇的擦拭之前申请的中性点接地的现场准备。 </li><li>确保过滤器设置为3赫兹（低频滤波器）和10kHz（高频滤波）之间。 </li><li>确保扫描速度被设定为20毫秒，或2毫秒/格。 </li><li>确保用于记录CMAP响应的灵敏度被设置为5毫伏。 </li><li>监测温度在刺激的部位在整个研究中，并确保该肢体的温度保持在32℃。 </li></ol> 4。分析与解读<ol><li>测量基线到峰值CMAP波幅（MV）在建业，FDI与ADM的肌肉在ALS患者和神经肌肉疾病的模拟控制。 </li><li>通过乘以记录在APB和FDI肌肉的CMAP的幅度，并通过记录在ADM肌肉的CMAP振幅除以这个产品，如下计算分割手指数（ 图1）: SI =建业* CMAP CMAP的外国直接投资 _________________________ ＆＃160; ADM CMAP </li><li>通过根据标准报告的诊断准确率（STARD）的标准比较ALS患者和神经肌肉的模仿障碍病理对照组之间的SI值确定拆分手指数的诊断工具。 </li><li>通过受试者工作特征（ROC）曲线确定为分体式手指数最佳诊断临界值。通过绘制灵敏度（y-轴）和1 - specificty（x-轴），用于从ALS和神经肌肉障碍的病人衍生的SI值推导出ROC曲线。 </li></ol>

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作者什么都没有透露。

本研究报告在ALS的一种新型的神经电生理诊断生物标志物拆分手指数的诊断工具。在SI可靠地区别于神经肌肉疾病的ALS，用5.2​​的最佳诊断临界值。在SI的减少是最突出的肢体起病的ALS患者。重要的是，被分类在诊断"可能"类别按照最近制定的诊断标准11 ALS患者相当大的比例，表现出异常的SI。综上所述，从目前的研究结果表明，拆分手指数可能是ALS的诊断生物标志物，在ALS的早期诊断有潜在帮助。 诊断标准，依靠在多个区域上和下运动神经元功能障碍的存在，已经开发了以有助于ALS 6，11，22的诊断。这些标准，然而，已被示出为不敏感，有时由于需要进行大量的针肌电采样7-10，14-16限制病人耐受性。因此，关键的诊断延误仍可能发生，也许以后的治疗窗口期。 拆分手指数，一个简单的神经生理学的生物标记物，可以在临床环境中可以容易地进行。重要的是，本研究强调拆分手指数在ALS的诊断工具，尤其是在肢体发病。的相关性，对发现的拆分手指数的下降是一个早期特征在ALS，进一步凸显了它的诊断工具。最终，SI的应用可能导致招募ALS患者进入临床试验，对疾病的过程，其中的未来神经保护剂的有效性可能是在高峰期的早期阶段。 拆分手指数的潜在限制可能发生的设置共存的聚焦压力mononeuropathies，尤其是腕管综合征及尺神经在肘部。临床神经生理学，和放射性相关性应该被利用来评估的病理学和替代技术，需要实现一个特定的模式，以便建立ALS 23,24的诊断。另外，SI可以在晚期疾病是有限的，当可能存在的固有手部肌肉全球萎缩。作为局灶性mononeuropathies，其他诊断方法应该被用来确认ALS的诊断。此外，避免从卷上的贡献进行回应CMAP波幅是缔结了SI的诊断价值之前的关键。量传导可通过记录电极适当定位可减小，以确保与负起飞和适当的刺激强度应当被用来防止交叉刺激一个CMAP响应。如果所有这些电位人限制是处理时，SI可以用作在ALS一个潜在的诊断辅助。

拆分手 ，指的是大鱼际复杂的组手内肌[拇短展肌（APB）和第一骨间背侧（FDI）]的优先萎缩，与小鱼际肌的相对保值，并且是肌萎缩的具体和早期临床特点侧索硬化症（ALS）1-4。这一发现，分割手势是具体 ​​的ALS，提出分手的手势在3 ALS诊断的生物标记物的潜在作用。 分割手势的量化，​​通过一种新颖的神经生理学的生物标志物的发展，可能会进一步帮助在ALS诊断。具体而言，分割手指数（SI），该量化的手裂现象，通过乘以复合肌肉动作电位（CMAP）衍生的振幅记录在鱼际复杂的肌肉（APB和FDI），以及由CMAP的幅度除以该商品记录在HYPothenar肌肉（即小指展肌，ADM）5。 ALS的诊断主要依赖临床为基础的标准，涵盖上，下运动神经元的组合标志6。这些标准，然而，被认为不敏感尤其是在疾病过程7-10的早期阶段建立的ALS的诊断。最近的诊断标准修改被开发11，尽管这些条件会提高诊断的敏感性12-16，增加灵敏度似乎仅限于延髓发病的ALS患者15。 在不存在的特征性的测试，ALS的诊断可显著延迟8。最终，神经保护疗法和招聘机构进入临床试验可能会延迟，也许超出了关键的治疗窗口期9，17。因此，该在SI的诊断工具进行前瞻性评估零星的ALS患者。

<table><tbody><tr><td>Abrasive gel (Nu Prep)</td><td>Weaver and Company</td><td>N-TA\/P\H-3 ENG</td><td>Skin preperation</td></tr><tr><td>Alcohol wipe</td><td>Triad Disposables</td><td>103101</td><td>Skin preperation</td></tr><tr><td>Recording gel (Ten20 Conductive gel)</td><td>Weaver and Company</td><td>N-TA\/P\H-3 ENG</td><td>Recording motor responses</td></tr><tr><td>Amyotrophic lateral sclerosis rating scale-revised questionnaire</td><td>Publication</td><td>Experimental builder</td><td>Stage disease</td></tr><tr><td>Medical Research Council muscle strength scale</td><td>Medical Research Council-UK</td><td>Experimental builder</td><td>Stage disease</td></tr><tr><td>&lt;strong&gt;Equipment&lt;/strong&gt;</td><td>&lt;strong&gt;Company&lt;/strong&gt;</td><td>&lt;strong&gt;Catalog number&lt;/strong&gt;</td><td>&lt;strong&gt;Comments&lt;/strong&gt;</td></tr><tr><td>Nerve conduction machine (Synergy/Nicolet EDX)</td><td>CareFusion</td><td>SA110106M</td><td>To measure split hand index</td></tr><tr><td>Synergy software</td><td>CareFusion</td><td>765654679</td><td>To measure split hand index</td></tr><tr><td>Tem millimeter gold cup disc electrodes</td><td>Grass Technologies</td><td>F-E5GH-60</td><td>To record motor responses</td></tr><tr><td>Neural earth plate</td><td>Westmead Hospital</td><td>Experimental builder</td><td>To record limb temperature</td></tr><tr><td>Thermometer</td><td>Westmead Hospital</td><td>Experimental builder</td><td>To record limb temperature</td></tr></tbody></table>

utility of dissociated intrinsic hand muscle atrophy in the diagnosis of amyotrophic lateral sclerosis

拆分手现象是指鱼际肌萎缩主要是与肌萎缩侧索硬化症（ALS）的早期和具体功能。一种新的分裂手指数（SI）的开发是为了量化分割手现象，其诊断实用程序是在ALS患者进行评估。拆分手指数除以的复合肌肉动作电位（CMAP）的产品导出的幅值记录在拇短展肌及第一背侧骨间肌被记录在小指展肌CMAP波幅。为了评估拆分手指数的诊断工具，ALS患者进行前瞻性评估及其结果进行了比较，神经肌肉障碍的病人。在ALS相比，神经肌肉疾病患者（P &lt;0.0001）拆分手指数显著降低。四肢发ALS患者表现出最大的减少在分割手指数，和一个值从其他神经肌肉疾病5.2或更低可靠地鉴别ALS。因此，分割手指数似乎是ALS的一种新颖的诊断生物标记物，或许有助于早期诊断。

临床表型 总体而言，44 ALS患者进行了研究，其中76％（N = 33）被列为明确或可能和24％（N = 11）尽可能ALS根据淡路标准11。 ALS诊断中的"可能"世代被证实后，在此期间广泛调查和临床随访长达3年，53％的患者死亡。延髓起病很明显在41％，而肢体发病在ALS患者的59％。在评估时，平均病程为18.9±3.1个月，中位ALSFRS-R评分为41（32-45），说明残疾的程度适中。 神经肌肉对照组包括121例患者（平均年龄54岁），包括下列诊断:压迫神经病变，腕管综合征（CTS）和尺神经在肘部（UNE），N = 62;脱髓鞘神经病变（n = 9）;感觉轴索神经病（n = 36）;宫颈卡尔神经根病（11）; spino-延髓肌肉萎缩症（N = 1）;平山病（N = 1）;脊髓性肌萎缩（N = 1）。 神经生理学的研究 在ALS患者中，有一个显著减少记录在建业CMAP波幅的（ALS，3.9±0.5毫伏;神经肌肉疾病8.1±0.2毫伏，P &lt;0.001），外国直接投资（ALS，4.8±0.7毫伏;神经肌肉疾病10.7±0.3毫伏，P &lt;0.001）和ADM（ALS，6.1±0.5毫伏;神经肌肉疾病9.7±0.2毫伏，P &lt;0.001）。和FDI（ 外商直接投资的CMAP 4.8±0.7毫伏; CMAP 霉素 6.1±0.5 mV的磷;重要的是，记录在建业（CMAP 霉素 6.1±0.5 mV的P &lt;0.001 CMAP APB 3.9±0.5毫伏）时，CMAP波幅降低是较为突出&lt;0.05），肌肉然后ADM在ALS的队列。 进一步的相关性，CMAP减幅为肢体起病的患者记录了一个时更加突出PB（CMAP 肢体起病 3.8±0.4毫伏; CMAP 延髓发病 5.3±0.6 mV的P &lt;0.05），外国直接投资（CMAP 肢体起病 4.4±0.7毫伏; CMAP 延髓发病 7.0±0.9 mV的P &lt;0.05），ADM（ CMAP 肢体起病 5.8±0.5毫伏; CMAP 延髓发病 7.6±0.6 mV的P均&lt;0.01）相比，延髓发病ALS患者的肌肉。相比之下，记录在建业（8.1±0.2毫伏，P &lt;0.0001）和阿霉素（9.7±0.2毫伏，P &lt;0.01）肌肉的神经肌肉队列（CMAP的外商直接投资 10.7±0.3毫伏时，CMAP波幅降低是最突出）。 结合CMAP振幅，很明显，有一个在ALS患者的一个显著减少拆分手指数相比，神经肌肉疾病患者（ALS 3.5±0.6;神经肌肉疾病9.1±0.3，P &lt;0.0001， 图2A）21。虽然这减少分裂手指数是UBiquitous发现在ALS，它是最明显的ALS患者肢体起病（SI 肢体起病 2.3±0.5，SI 延髓发病 5.3±1.2，P &lt;0.0001， 图2B）21。 所公开的接受者操作特性曲线分析拆分手指数，良好的诊断准确性在从其他神经肌肉疾病鉴别ALS的，由一个事实，即曲线下的面积（AUC）为0.83（P &lt;0.0001， 图3A）21所指示的。来自其它神经肌肉障碍21 5.2或更低，由虚线的黑线（ 图3A）所示，分化的ALS的SI值。重要的是，拆分手指数的诊断实用程序是更大的ALS患者肢体起病（ 图3B）21。 为了评估拆分手指数的诊断实用程序，SI值吨之间的比较软管满足了"明确的"与上淡路岛的标准11"可能"的诊断范畴ALS患者。重要的是，在分类为"可能"ALS患者的一个显著减少的SI（ALS 可能 SI 5.1±0.8;神经肌肉疾病9.1±0.3，P &lt;0.01）。列为可能的ALS的11例患者中，此外，有64％表现出在小于5.2拆分手指数值的降低。总之，这些研究结果表明，异常分裂手指数可能支持ALS的诊断高达64％的患者不符合"确定/可能"淡路的诊断标准。 潜在的预后的相关性，与MRC的总成绩显著相关性拆分手指数（卢= 0.7，P &lt;0.001）和MRC评分从鱼际（卢= 0.8，P &lt;0.001）。进一步的相关性，在SI表现出显著相关性疾病编率ression（rho沸石= - 0.4，P &lt;0.05）。这些结果表明，SI是与疾病的严重程度和进展有关，因而暗示对在SI中ALS的预测的潜在作用。 <img alt="图1" fo:content-width="5in" fo:src="/files/ftp_upload/51056/51056fig1highres.jpg" src="/files/ftp_upload/51056/51056fig1.jpg" /> 图1。分割手势指的是复杂的大鱼际肌肉群[拇短展肌（APB）和第一骨间背侧（FDI）]肌肉相比，小鱼际[诱拐数字MINIMI（ADM）]的肌肉。分割的手指数是优先消耗乘以复合肌肉动作电位由记录在外国直接投资录得超过建业（CMAP）波幅和产品通过记录在ADM的CMAP波幅来计算的。 （部分来自梅农和他的同事转载。拆分手指数amyotr的诊断ophic侧索硬化症。从梅农等人 21 <img alt="图2" fo:content-width="5in" fo:src="/files/ftp_upload/51056/51056fig2highres.jpg" src="/files/ftp_upload/51056/51056fig2.jpg" /> 图2。 （一）拆分手指数（SI）是显著的肌萎缩侧索硬化症（ALS）相比，神经肌肉疾病患者（NMS）减少（B）以SI的减少是最突出的在ALS患者的肢体起病。 *** P &lt;0.001; ** p &lt;0.0001。 <img alt="图3" fo:content-width="5in" fo:src="/files/ftp_upload/51056/51056fig3highres.jpg" src="/files/ftp_upload/51056/51056fig3.jpg" /> 图3。 （一）拆分手指数（SI）从神经肌肉疾病患者（NMS）的强劲差异化的肌萎缩侧索硬化症（ALS），具有最佳直径诺斯底截止值为5.2（B）SI的诊断工具是比较突出的肢体起病的ALS患者。 （部分来自梅农和他的同事转载。拆分手指数为肌萎缩侧索硬化症的诊断。从梅农等人 21

Watch this Scientific Journal Video about Utility of Dissociated Intrinsic Hand Muscle Atrophy in the Diagnosis of Amyotrophic Lateral Sclerosis at JoVE.com

Utility of Dissociated Intrinsic Hand Muscle Atrophy in the Diagnosis of Amyotrophic Lateral Sclerosis

固有手部肌肉游离萎缩，称为分体式手，似乎是肌萎缩侧索硬化症（ALS）的特定功能。因此，一种新的神经诊断测试，称为裂手指数 ，被开发来量化拆分手的临床现象，这区别ALS从模拟紊乱。

在肌萎缩侧索硬化症的诊断游离本质手部肌肉萎缩实用工具

The split hand phenomenon refers to predominant wasting of thenar muscles and is an early and specific feature of amyotrophic lateral sclerosis (ALS). A ...

utility-dissociated-intrinsic-hand-muscle-atrophy-diagnosis

Nanyang Technological University

Research

JoVE Journal

Medicine

31.5K 次观看.  Westmead Hospital. 固有手部肌肉游离萎缩，称为分体式手，似乎是肌萎缩侧索硬化症（ALS）的特定功能。因此，一种新的神经诊断测试，称为裂手指数 ，被开发来量化拆分手的临床现象，这区别ALS从模拟紊乱。 

视频: Utility of Dissociated Intrinsic Hand Muscle Atrophy in the Diagnosis of Amyotrophic Lateral Sclerosis

A Protocol for Comprehensive Assessment of Bulbar Dysfunction in Amyotrophic Lateral Sclerosis (ALS)

Improved methods for assessing bulbar impairment are necessary for expediting diagnosis of bulbar dysfunction in ALS, for predicting disease progression across speech subsystems, and for addressing the critical need for sensitive outcome measures for ongoing experimental treatment trials. To address this need, we are obtaining longitudinal profiles of bulbar impairment in 100 individuals based on a comprehensive instrumentation-based assessment that yield objective measures. Using instrumental approaches to quantify speech-related behaviors is very important in a field that has primarily relied on subjective, auditory-perceptual forms of speech assessment1. Our assessment protocol measures performance across all of the speech subsystems, which include respiratory, phonatory (laryngeal), resonatory (velopharyngeal), and articulatory. The articulatory subsystem is divided into the facial components (jaw and lip), and the tongue. Prior research has suggested that each speech subsystem responds differently to neurological diseases such as ALS. The current protocol is designed to test the performance of each speech subsystem as independently from other subsystems as possible. The speech subsystems are evaluated in the context of more global changes to speech performance. These speech system level variables include speaking rate and intelligibility of speech.
The protocol requires specialized instrumentation, and commercial and custom software. The respiratory, phonatory, and resonatory subsystems are evaluated using pressure-flow (aerodynamic) and acoustic methods. The articulatory subsystem is assessed using 3D motion tracking techniques. The objective measures that are used to quantify bulbar impairment have been well established in the speech literature and show sensitivity to changes in bulbar function with disease progression. The result of the assessment is a comprehensive, across-subsystem performance profile for each participant. The profile, when compared to the same measures obtained from healthy controls, is used for diagnostic purposes. Currently, we are testing the sensitivity and specificity of these measures for diagnosis of ALS and for predicting the rate of disease progression. In the long term, the more refined endophenotype of bulbar ALS derived from this work is expected to strengthen future efforts to identify the genetic loci of ALS and improve diagnostic and treatment specificity of the disease as a whole. The objective assessment that is demonstrated in this video may be used to assess a broad range of speech motor impairments, including those related to stroke, traumatic brain injury, multiple sclerosis, and Parkinson disease.

A Protocol for Comprehensive Assessment of Bulbar Dysfunction in Amyotrophic Lateral Sclerosis ALS

Objective assessments of the physiological mechanisms that support speech are needed to monitor disease onset and progression in persons with ALS and to quantify treatment effects in clinical trials. In this video, we present a comprehensive, instrumentation-based protocol for quantifying speech motor performance in clinical populations.

延髓功能障碍肌萎缩性脊髓侧索硬化症（ALS）的综合评估议定书

Improved methods for assessing bulbar impairment are necessary for expediting diagnosis of bulbar dysfunction in ALS, for predicting disease progression ...

科研

医学

Manual Muscle Testing:  A Method of Measuring Extremity Muscle Strength Applied to Critically Ill Patients 

Survivors of acute respiratory distress syndrome (ARDS) and other causes of critical illness often have generalized weakness, reduced exercise tolerance, and persistent nerve and muscle impairments after hospital discharge.1-6 Using an explicit protocol with a structured approach to training and quality assurance of research staff, manual muscle testing (MMT) is a highly reliable method for assessing strength, using a standardized clinical examination, for patients following ARDS, and can be completed with mechanically ventilated patients who can tolerate sitting upright in bed and are able to follow two-step commands. 7, 8 
This video demonstrates a protocol for MMT, which has been taught to &ge;43 research staff who have performed &gt;800 assessments on &gt;280 ARDS survivors. Modifications for the bedridden patient are included. Each muscle is tested with specific techniques for positioning, stabilization, resistance, and palpation for each score of the 6-point ordinal Medical Research Council scale.7,9-11 Three upper and three lower extremity muscles are graded in this protocol: shoulder abduction, elbow flexion, wrist extension, hip flexion, knee extension, and ankle dorsiflexion. These muscles were chosen based on the standard approach for evaluating patients for ICU-acquired weakness used in prior publications. 1,2.

Manual Muscle Testing:  A Method of Measuring Extremity Muscle Strength Applied to Critically Ill Patients

Survivors of acute respiratory distress syndrome (ARDS) and critical illness frequently develop long-lasting muscle weakness. Manual muscle testing (MMT) is a standardized clinical examination commonly used to measure strength of peripheral skeletal muscle groups. This video demonstrates MMT using the 6-point Medical Research Council scale.

危重病人中的应用手册肌力测试：下肢肌力测量方法

Survivors of acute respiratory distress syndrome (ARDS) and other causes of critical illness often have generalized weakness, reduced exercise tolerance, ...

Electrophysiological Motor Unit Number Estimation (MUNE) Measuring Compound Muscle Action Potential (CMAP) in Mouse Hindlimb Muscles

Compound muscle action potential (CMAP) and motor unit number estimation (MUNE) are electrophysiological techniques that can be used to monitor the functional status of a motor unit pool in vivo. These measures can provide insight into the normal development and degeneration of the neuromuscular system. These measures have clear translational potential because they are routinely applied in diagnostic and clinical human studies. We present electrophysiological techniques similar to those employed in humans to allow recordings of mouse sciatic nerve function. The CMAP response represents the electrophysiological output from a muscle or group of muscles following supramaximal stimulation of a peripheral nerve. MUNE is an electrophysiological technique that is based on modifications of the CMAP response. MUNE is a calculated value that represents the estimated number of motor neurons or axons (motor control input) supplying the muscle or group of muscles being tested. We present methods for recording CMAP responses from the proximal leg muscles using surface recording electrodes following the stimulation of the sciatic nerve in mice. An incremental MUNE technique is described using submaximal stimuli to determine the average single motor unit potential (SMUP) size. MUNE is calculated by dividing the CMAP amplitude (peak-to-peak) by the SMUP amplitude (peak-to-peak). These electrophysiological techniques allow repeated measures in both neonatal and adult mice in such a manner that facilitates rapid analysis and data collection while reducing the number of animals required for experimental testing. Furthermore, these measures are similar to those recorded in human studies allowing more direct comparisons.

Electrophysiological Motor Unit Number Estimation MUNE Measuring Compound Muscle Action Potential CMAP in Mouse Hindlimb Muscles

We present refined protocols that allow in vivo monitoring of motor unit function in the mouse. Techniques to measure compound muscle action potential (CMAP) and motor unit number estimation (MUNE) in the mouse hind limb muscles innervated by the sciatic nerve are described.

电电机组数估计（MUNE）在小鼠后肢肌肉测量复合肌肉动作电位（CMAP）

Compound muscle action potential (CMAP) and motor unit number estimation (MUNE) are electrophysiological techniques that can be used to monitor the ...

行为学

Clinical Testing and Spinal Cord Removal in a Mouse Model for Amyotrophic Lateral Sclerosis (ALS)

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder resulting in progressive degeneration of motoneurons. Peak of onset is around 60 years for the sporadic disease and around 50 years for the familial disease. Due to its progressive course, 50% of the patients die within 30 months of symptom onset. In order to evaluate novel treatment options for this disease, genetic mouse models of ALS have been generated based on human familial mutations in the SOD gene, such as the SOD1 (G93A) mutation. Most important aspects that have to be evaluated in the model are overall survival, clinical course and motor function. Here, we demonstrate the clinical evaluation, show the conduction of two behavioural motor tests and provide quantitative scoring systems for all parameters. Because an in depth analysis of the ALS mouse model usually requires an immunohistochemical examination of the spinal cord, we demonstrate its preparation in detail applying the dorsal laminectomy method. Exemplary histological findings are demonstrated. The comprehensive application of the depicted examination methods in studies on the mouse model of ALS will enable the researcher to reliably test future therapeutic options which can provide a basis for later human clinical trials.

Clinical Testing and Spinal Cord Removal in a Mouse Model for Amyotrophic Lateral Sclerosis ALS

A mouse model for amyotrophic lateral sclerosis (ALS) is examined clinically and behaviorally. As a prerequisite for an accompanying immunohistological analysis the preparation of the spinal cord is depicted in detail.

临床试验和脊髓去除在肌萎缩性侧索硬化症的小鼠模型（ALS）

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder resulting in progressive degeneration of motoneurons. Peak of onset is around 60 ...

Measuring Neuromuscular Junction Functionality

Neuromuscular junction (NMJ) functionality plays a pivotal role when studying diseases in which the communication between motor neuron and muscle is impaired, such as aging and amyotrophic lateral sclerosis (ALS). Here we describe an experimental protocol that can be used to measure NMJ functionality by combining two types of electrical stimulation: direct muscle membrane stimulation and the stimulation through the nerve. The comparison of the muscle response to these two different stimulations can help to define, at the functional level, potential alterations in the NMJ that lead to functional decline in muscle.
Ex vivo preparations are suited to well-controlled studies. Here we describe an intensive protocol to measure several parameters of muscle and NMJ functionality for the soleus-sciatic nerve preparation and for the diaphragm-phrenic nerve preparation. The protocol lasts approximately 60 min and is conducted uninterruptedly by means of a custom-made software that measures the twitch kinetics properties, the force-frequency relationship for both muscle and nerve stimulations, and two parameters specific to NMJ functionality, i.e. neurotransmission failure and intratetanic fatigue. This methodology was used to detect damages in soleus and diaphragm muscle-nerve preparations by using SOD1G93A transgenic mouse, an experimental model of ALS that ubiquitously overexpresses the mutant antioxidant enzyme superoxide dismutase 1 (SOD1).

A functional assessment of the neuromuscular junction (NMJ) can provide essential information on the communication between muscle and nerve. Here we describe a protocol to comprehensively evaluate both the NMJ and muscle functionality using two different muscle-nerve preparations, i.e. soleus-sciatic and diaphragm-phrenic.

测量神经肌肉接头功能

Neuromuscular junction (NMJ) functionality plays a pivotal role when studying diseases in which the communication between motor neuron and muscle is ...

神经科学

Repeated Measurement of Respiratory Muscle Activity and Ventilation in Mouse Models of Neuromuscular Disease

Accessory respiratory muscles help to maintain ventilation when diaphragm function is impaired. The following protocol describes a method for repeated measurements over weeks or months of accessory respiratory muscle activity while simultaneously measuring ventilation in a non-anesthetized, freely behaving mouse. The technique includes the surgical implantation of a radio transmitter and the insertion of electrode leads into the scalene and trapezius muscles to measure the electromyogram activity of these inspiratory muscles. Ventilation is measured by whole-body plethysmography, and animal movement is assessed by video and is synchronized with electromyogram activity. Measurements of muscle activity and ventilation in a mouse model of amyotrophic lateral sclerosis are presented to show how this tool can be used to investigate how respiratory muscle activity changes over time and to assess the impact of muscle activity on ventilation. The described methods can easily be adapted to measure the activity of other muscles or to assess accessory respiratory muscle activity in additional mouse models of disease or injury.

This paper introduces a method for repeated measurements of ventilation and respiratory muscle activity in a freely behaving amyotrophic lateral sclerosis (ALS) mouse model throughout disease progression with whole-body plethysmography and electromyography via an implanted telemetry device.

在神经肌肉疾病的模型小鼠呼吸肌肉活动和通风的重复测量

Accessory respiratory muscles help to maintain ventilation when diaphragm function is impaired. The following protocol describes a method for repeated ...

In Vivo Electrophysiological Measurement of Compound Muscle Action Potential from the Forelimbs in Mouse Models of Motor Neuron Degeneration

Assessing the functionality of the nerve axon provides detailed information on the progression of neuromuscular disorders. Electrophysiological recordings provide a sensitive approach to measure nerve conduction in humans and rodent models. To broaden the technical possibilities for electromyography in mice, the measurement of compound muscle action potentials (CMAPs) from the brachial plexus nerve in the forelimb using needle electrodes is described here. CMAP recordings after stimulating the sciatic nerve in hindlimbs have been previously described. The newly introduced method here allows for the evaluation of the nerve conductivity at an additional site, and thus provides a more profound overview of the neuromuscular functionality. The technique provides information on both the relative number of functional axons and the myelination level. Thereby, this method can be applied to assess both axonal diseases as well as demyelinating conditions. This minimally invasive method does not require extraction of the nerve and therefore it is suitable for repeated measurements for longitudinal follow-up in the same animal. Similar recordings are performed in clinical setups to emphasize the translational relevance of the method.

In Vivo Electrophysiological Measurement of Compound Muscle Action Potential from the Forelimbs in Mouse Models of Motor Neuron Degeneration

The measurement of nerve conduction is a useful tool to assess mouse models of neurodegeneration but it is frequently only applied to stimulate the sciatic nerve in hindlimbs. Here, we describe a technique to measure compound muscle action potential (CMAP) in vivo in the mouse forelimb muscles innervated by the brachial plexus.

体内运动神经元变性小鼠前肢肌作用电位的电生理测量

Assessing the functionality of the nerve axon provides detailed information on the progression of neuromuscular disorders. Electrophysiological recordings ...

The Muscle Cuff Regenerative Peripheral Nerve Interface for the Amplification of Intact Peripheral Nerve Signals

Robotic exoskeletons have gained recent acclaim within the field of rehabilitative medicine as a promising modality for functional restoration for those individuals with extremity weakness. However, their use remains largely confined to research institutions, frequently operating as a means of static extremity support as motor detection methods remain unreliable. Peripheral nerve interfaces have arisen as a potential solution to this shortcoming; however, due to their inherently small amplitudes, these signals can be difficult to differentiate from background noise, lowering their overall motor detection accuracy. As current interfaces rely on abiotic materials, inherent material breakdown can occur alongside foreign body tissue reaction over time, further impacting their accuracy. The Muscle Cuff Regenerative Peripheral Nerve Interface (MC-RPNI) was designed to overcome these noted complications. Consisting of a segment of free muscle graft secured circumferentially to an intact peripheral nerve, the construct regenerates and becomes reinnervated by the contained nerve over time. In rats, this construct has demonstrated the ability to amplify a peripheral nerve's motor efferent action potentials up to 100 times the normal value through the generation of compound muscle action potentials (CMAPs). This signal amplification facilitates high accuracy detection of motor intent, potentially enabling reliable utilization of exoskeleton devices.

This manuscript provides an innovative method for developing a biologic peripheral nerve interface termed the Muscle Cuff Regenerative Peripheral Nerve Interface (MC-RPNI). This surgical construct can amplify its associated peripheral nerve's motor efferent signals to facilitate accurate detection of motor intent and the potential control of exoskeleton devices.

肌袖再生周围神经接口，用于放大完整的周围神经信号

Robotic exoskeletons have gained recent acclaim within the field of rehabilitative medicine as a promising modality for functional restoration for those ...

生物工程

Isometric and Eccentric Force Generation Assessment of Skeletal Muscles Isolated from Murine Models of Muscular Dystrophies

Critical to the evaluation of potential therapeutics for muscular disease are sensitive and reproducible physiological assessments of muscle function. Because many pre-clinical trials rely on mouse models for these diseases, isolated muscle function has become one of the standards for Go/NoGo decisions in moving drug candidates forward into patients. We will demonstrate the preparation of the extensor digitorum longus (EDL) and diaphragm muscles for functional testing, which are the predominant muscles utilized for these studies. The EDL muscle geometry is ideal for isolated muscle preparations, with two easily accessible tendons, and a small size that can be supported by superfusion in a bath. The diaphragm exhibits profound progressive pathology in dystrophic animals, and can serve as a platform for evaluating many potential therapies countering fibrosis, and promoting myofiber stability. Protocols for routine testing, including isometric and eccentric contractions, will be shown. Isometric force provides assessment of strength, and eccentric contractions help to evaluate sarcolemma stability, which is disrupted in many types of muscular dystrophies. Comparisons of the expected results between muscles from wildtype and dystrophic muscles will also be provided. These measures can complement morphological and biochemical measurements of tissue homeostasis, as well as whole animal assessments of muscle function.

Muscle function measurements contribute to the evaluation of potential therapeutics for muscle pathology, as well as to the determination of mechanisms underlying physiology of this tissue. We will demonstrate the preparation of the extensor digitorum longus and diaphragm muscles for functional testing. Protocols for isometric and eccentric contractions will be shown, as well as differences in results between dystrophic muscles, representing a pathological state, and wildtype muscles.

等距和骨骼肌产生偏心力评估隔离肌营养不良症的小鼠模型

Critical to the evaluation of potential  therapeutics for muscular disease are sensitive and reproducible physiological  assessments of muscle function. ...

生物学

<meta charset="utf8"></head><body>量化神经退行性啮齿动物模型中的膈运动单位功能

Assessing Rat Diaphragm Motor Unit Connectivity Outcome Measures as Quantitative Biomarkers of Phrenic Motor Neuron Degeneration and Compensation

Loss of ventilatory muscle function is a consequence of motor neuron injury and neurodegeneration (e.g., cervical spinal cord injury and amyotrophic lateral sclerosis, respectively). Phrenic motor neurons are the final link between the central nervous system and muscle, and their respective motor units (groups of muscle fibers innervated by a single motor neuron) represent the smallest functional unit of the neuromuscular ventilatory system. Compound muscle action potential (CMAP), single motor unit potential (SMUP), and motor unit number estimation (MUNE) are established electrophysiological approaches that enable the longitudinal assessment of motor unit integrity in animal models over time but have mostly been applied to limb muscles. Therefore, the objectives of this study are to describe an approach in preclinical rodent studies that can be used longitudinally to quantify the phrenic MUNE, motor unit size (represented as SMUP), and CMAP, and then to demonstrate the utility of these approaches in a motor neuron loss model. Sensitive, objective, and translationally relevant biomarkers for neuronal injury, degeneration, and regeneration in motor neuron injury and diseases can significantly aid and accelerate experimental research discoveries to clinical testing.

<meta charset="utf8"></head><body>作者聚焦：研究神经退行性疾病中的神经肌肉反应和运动神经元可塑性

In this study, we present an in vivo method for estimating motor unit number and size to quantify rat diaphragm motor unit connectivity. A step-by-step approach to these techniques is described.

评估大鼠膈肌运动单元连接结果测量作为膈运动神经元变性和代偿的定量生物标志物

Loss of ventilatory muscle function is a consequence of motor neuron injury and neurodegeneration (e.g., cervical spinal cord injury and amyotrophic ...