这项工作已经由美国国立卫生研究所，国立耳聋与其他交流障碍研究所，格兰特R01DCO09890 - 02，加拿大创新基金会（原讼法庭的LOF＃15704），及干诺基金会，加拿大多伦多大学的支持。作者想感谢协助数据收集和分析，米利Kuruvilla辛西娅迪迪翁，克里斯塔鲁迪，洛瑞Syn​​horst;和Cara乌尔曼创建视频剪辑。 动画蓝树出版社（ <a href="http://www.bluetreepublishing.com/">http://www.bluetreepublishing.com/</a> ） SPA和SMASH软件是基于Matlab可以联系jgreen4@unl.edu约旦绿色获得。 访问我们的实验室： <ul><li>延髓功能研究实验室（Sunnybrook健康科学中心在多伦多，加拿大）： <ul><li> <a href="http://www.sunnybrook.ca/research/?page=sri_groups_bulb_home">http://www.sunnybrook.ca/research/?page=sri_groups_bulb_home</a> </li></ul></li><li>语音生产实验室（内布拉斯加林肯大学）： <ul><li> <a href="http://spl.unl.edu">http://spl.unl.edu</a> </li></ul></li></ul>

一，子系统分析 1。呼吸子系统/呼吸讲话呼吸评估子系统使用的发声空气动力学系统（PAS）。该系统可以同时录音，口头压力，气流，和语音声学（见设备和制造商名单表1）。一次性口罩和一次性管压力传感录音是必要的。录音之前，流量和压力的渠道是根据制造商的规格校准。 <ol><li> 肺活量（VC），是呼出的最大吸入的空气最大音量。 VC是评估使用一次性口罩，是连接到pneumotachograph。 <ol class="lalpha"><li>考绩制度的“肺活量”协议被选中的记录。 </li><li>指示参与者吸入最大限度地尽可能最大限度呼气成面具;任务是重复三次。 </li><li>最大呼气量推导出保安局首席助理局长软件。 </li></ol></li><li> 声门下压力（PS）生产的“压力”辅音在肺部的空气压力。 PS被评为间接测量生产过程中的一个音节的列车 2,3口的压力峰值。 <ol class="lalpha"><li>考绩制度的“清浊效率”协议被选中的记录。 </li><li>要记录在/ PA /压力传感管内口在舌头上表面定位的口头压力。 </li><li>鼻腔闭塞用鼻夹，以消除潜在的鼻腔空气流量逃生。 </li><li>参与者被指示吸入约两倍的正常量，并说，PA / /进入面罩。音节/ PA /重复七次之一呼气，同时保持一贯的音调和响度。率维持在1.5％，第二个音节。 </li><li>五（中）/ PA /重复测量山顶的口头压力。这五个生产的平均获得代表在讲话PS。 </li><li>由于PS声压级（SPL），4,5 covaries，声压级也收集的每一个音节。它是用来作为协变量随后在分析。 </li></ol></li><li> 语音呼吸是在连接的讲话进行评估，与会者读一个标准的60字第（附录1），专门开发为准确， 自动暂停边界检测6。 <ol class="lalpha"><li>考绩制度“最大发声”的协议被选中的记录。 </li><li>气流信号被收集使用一次性口罩，适合周围的脸。 </li><li>参与者被指示阅读该段在其正常舒适的语速和音量。 </li><li>空气流动的痕迹都导出到一个特制的语音暂停分析（SPA）在MATLAB 7软件程序。在这个程序中，连接语音停顿识别。该软件计算，除其他措施外，百分之暂停时间，这是一个衡量的时间花费在暂停过程中的一段话读。 </li></ol></li></ol> 2。发声子系统发声子系统评估通过语音录音，采用高品质的声学的录音设备（见表1）。 <ol class="lalpha"><li>麦克风放在离口约15厘米。 </li><li>鼻夹是用来消除腭咽不足的发声质量的潜在影响。 </li><li>参与者被要求出示“最大发声”。他或她是指示吸入空气的最高金额，然后发声/ /在一个正常的音调和尽可能长时间的响度。这个任务是实行至少一次到录音前。强调提出尽最大的努力的重要性。 </li><li>最大发声时间是在使用秒的声波波形测量。 </li><li>数字化声波形加载到多维语音简介（MDVP）软件进行分析。集中趋势和变异的基本频率（F0），噪声谐波比（NHR）和百分之抖动的措施，等等，都取得了中间的发声间隔5秒。 </li></ol> 3。 Resonatory子系统 resonatory子系统评估使用Nasometer。这种装置由一个耳机一个挡板，这是定位下鼻子和口腔和鼻腔分隔。两个麦克风，检测口腔和鼻腔的声波信号被连接到两侧的板块。 <ol class="lalpha"><li>每次录音前校准设备。 </li><li>耳机放置在头部，上唇以上的休息板与挡板和平行的grounD. </li><li>参与者被要求重复一个“鼻”（例如，妈妈做了一些柠檬果酱）和一个“非鼻”（例如，购买一只小狗鲍比）在一个惯常的语速和音量的句子三次。 </li><li>表示部分的口腔和鼻腔的声波信号的测量强度转换成一个nasalance得分，这是定义为鼻腔/鼻+口腔声波能量的比例，以百分比表示。 nasalance得分，反映了在一次讲话中流 8鼻腔到口腔的声波能量的相对比例。 </li><li> Nasometer软件计算众多的描述性统计，从nasalance波形。 </li><li> Nasalance距离，这是整个口腔的句子（BBP）的计算平均鼻句子（MMJ）9 nasalance减去平均nasalance派生，也可用于腭咽减值指数。 </li></ol> 4。关节子系统：脸部面部运动（唇和下巴）是注册在3D使用了高分辨率，光学运动捕捉系统10。红外数码摄像机捕捉15连接到每个参与者的头，面对特定的解剖标志的反光标记的位置。声学语音信号，同时记录讲话运动学。 <ol class="lalpha"><li>该系统校准录音前根据制造商的规格。 </li><li>四种标记物连接到前额使用头箍的参与者。标记也与左，右眉，桥梁和鼻尖，上下唇唇红，左，右弯道口，和下巴上的三个不同地点。这是典型的在本议定书中所使用的标记数组，但可以用本系统中使用的标记的数量不受限制。 </li><li>参与者被要求读句子和短语（见表2），在其惯常的语速和音量。 </li><li>获得一个“休息”的文件记录，并在处理后用于标记放置到符合需要的解剖学为基础的坐标系统之间的会话和重新表达数据的相对差异正常化。 </li><li>在处理后，面部标记的变动对跟踪误差进行检查和头部校正的基础上减去头部运动的平移和旋转部件。 </li><li> SMASH，在我们的实验室开发的一个基于MATLAB软件程序装入数据。在粉碎，数据筛选和分析。山顶的移动速度是来自每个跟踪和使用的下巴和嘴唇发音功能的主要指标。 3D速度是每个发音器官的欧几里德距离SMASH时间历史的一阶导数计算。 </li></ol> 5。关节子系统：舌使用电磁跟踪装置（波），它记录的位置和旋转传感器连接到舌舌跟踪完成。不像是用来记录外部，面部结构的光学运动跟踪，电磁技术提供了一种方法，准确地跟踪在讲话 11舌头的动作。该系统采用了组合5和6度自由（5DOF和6DOF ）传感器记录在校准量的关节运动（30 × 30 × 30厘米）。同时收购了移动数据和声学数据。 <ol class="lalpha"><li>两个传感器连接到使用牙科的胶（PeriAcryl牙周粘合剂）​​的发音器官。一个引用连接到鼻梁，记录头部动作。一个小5DOF的传感器（三维位置和角度测量2D）是附着在中线的舌头，舌尖后约2厘米。 </li><li>为了获得舌头的运动是独立于底层颚，每个参与者都配有一个前5毫米咬块。咬块是由无毒凝结腻子（亨利施恩）。 </li><li>咬块之间放置口一侧磨牙。咬块连接字符串是固定的参与者的脸上，以防止咬块吞咽。 </li><li>参与者被要求读句子和短语（见表2）。 </li><li>舌运动记录相头位置。 </li><li>收购后，数据转移到粉碎，它是低通滤波，垂直运动轨迹的基础上分析，并用于计算三维速度。运动的平均及最高速度在每个话语是这个发音器官疾病相关的变化的指数报告。 </li></ol>二。系统级评估此外子系统级的变量，语音清晰度和语速进行测量。这些测量sures是必不可少的，因为它们是目前临床上的“目标标准”，延髓讲话性能。他们提供了一个讲话的生产系统作为一个整体的功能状态指示和量化的言语障碍的严重性。这些措施取得使用句子的清晰度测试（SIT），12。 <ol class="lalpha"><li>录制之前，产生一个随机的10个句子长度增加（从5到15个字）清单是由薛软件。 </li><li>一个麦克风被放置在头，从口入约15厘米。 </li><li>参与者被要求在其惯常的语速和音量阅读列表。数字记录在使​​用一个16位分辨率的44.1K的句子。 </li><li>一些受过训练的法官来说是陌生的参与者抄写句子拼写和衡量句子工期。 </li><li>静坐的软件会自动计算语音可懂度，这是正确转录生产的单词总数的字％报告。语速为每分钟读字数目也有报道。 </li></ol><table border="1"><tbody><tr><td>子系统</td><td>设备/软件</td><td>信号</td><td>采集设置</td></tr><tr><td>呼吸系统</td><td>发声空气动力学系统（PAS），KayPENTAX，林肯公园，美国新泽西州</td><td>声学，压力，流量</td><td>采样率= 200赫兹，低通滤波= 30HZ </td></tr><tr><td>发声</td><td>紧凑型闪存录像机（例如，PMD660） 专业品质麦克风， 华仪仪器仪表，声压级 软件：MDVP，KAYPentax </td><td>声</td><td>采样率= 44.01 kHz，16位线性PCM </td></tr><tr><td> Resonatory </td><td> Nasometer，型号6400，KAYPentax </td><td>声</td><td>采样率= 11025赫兹</td></tr><tr><td>关节：面</td><td>鹰数字系统，运动分析公司</td><td>运动学和声学</td><td>采样率= 120Hz的低通滤波= 10HZ </td></tr><tr><td>关节：母语</td><td>波，北数码公司，加拿大</td><td>运动学和声学</td><td>采样率= 100Hz的低通滤波= 20HZ </td></tr></tbody></table>表1：亚系统的数据收集仪器和采集设置<table border="1"><tbody><tr><td>等级</td><td>任务</td><td>测量</td><td>参考及规范</td></tr><tr><td>呼吸系统</td><td> VC + + </td><td>最大呼气时肺容积</td><td> 13 </td></tr><tr><td> / PA / X 7 </td><td>声门下压力</td><td> 2，3 </td></tr><tr><td>竹通过</td><td> ％暂停时间</td><td> 6，7，14 </td></tr><tr><td>发声</td><td>最大发声/ A / </td><td>最大发声时间，平均基频，抖动，信噪比</td><td> 15，16，17，3 </td></tr><tr><td> Resonatory </td><td>妈妈做了一些柠檬果酱;购买鲍比的小狗</td><td> Nasalance </td><td> 18，19 </td></tr><tr><td>关节：面</td><td>购买鲍比一只小狗;说_（BAT，潮流，保持，工具），再</td><td>移动速度</td><td> 20，21 </td></tr><tr><td>关节：母语</td><td> / TA / X 5，再次说桌巾</td></tr><tr><td>系统级</td><td>薛，句子</td><td>语音清晰度和语速</td><td> 12 </td></tr></tbody></table>表2：各子系统和任务得到的测量附录1：竹通道竹墙壁变得非常受欢迎。他们强，易于使用，而且好看。他们提供了一个良好的背景和创造的日本庭园的情绪。竹子是一种草，是在世界上增长最迅速的的的草。许多品种的竹子生长在亚洲，虽然它也是在美国长大。去年，我们买了一个新的家，并已在花坛工作。再过几天，我们将在我们的花园之一的竹墙。我们很喜欢的项目。

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L., aZinman, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Kinematics+of+disease+progression+in+bulbar+ALS.">Kinematics of disease progression in bulbar ALS.</a> J Commun. Disord. 43, 6-20 (2010).</li></ol>

在这里，我们展示了一个全面的协议球的评估（讲话）在ALS功能障碍。从本议定书中所取得的数据是如何ALS的影响讲话的生产，从而获得更深入的了解。这些数据也被用来确定病情恶化的最敏感的措施。虽然这个协议是目前受聘为研究，这项研究的结果将被用来开发更具成本效益和临床上是可行的办法，量化延髓参与。

<ul><li>设备/软件</li><li>发声空气动力学系统（PAS），KayPENTAX，林肯公园，美国新泽西州</li><li>紧凑型闪存录像机（例如，PMD660） </li><li>专业品质麦克风， </li><li>华仪仪器仪表，声压级</li><li> MDVP，KAYPentax </li><li> Nasometer，型号6400，KAYPentax </li><li>鹰数字系统，运动分析公司</li><li>波，北数码公司，加拿大</li></ul>

a protocol for comprehensive assessment of bulbar dysfunction in amyotrophic lateral sclerosis (als)

改进评估延髓减值方法，为加快在ALS延髓功能障碍的诊断，预测病情恶化跨讲话子系统，并为解决敏感正在进行的实验治疗试验结果措施的迫切需要的必要。为了满足这一需要，我们是一个全面的仪器为基础的评估措施，产量目标为基础的100人获得延髓减值的纵剖面。使用工具的方法来量化语音相关的行为，在一个主要依靠主观的，感性的听觉言语评估1形式的领域是非常重要的。我们的评估协议的措施，在所有讲话子系统，其中包括呼吸，发声（喉），resonatory（腭咽），和关节的性能。关节子系统分为面部组件（下巴和嘴唇），和舌头。此前的研究曾建议每个语音子系统神经系统疾病如ALS的反应不同。目前的协议的目的是尽可能独立地从其他子系统的每个语音子系统的性能进行测试。讲话子系统在讲话性能全球变化的背景下进行评估。这些语音系统级变量包括语速讲话和可懂度。 该协议需要专门的仪器仪表，商业和定制软件。呼吸，发声，resonatory子系统采用压力流（气动）和声学方法进行评估。关节子系统是使用三维运动跟踪技术进行评估。所使用的量化延髓减值的客观措施已确立在讲话中文学和敏感性延髓功能与疾病进展的变化。评估的结果是一个全面的，跨子系统，每个参与者性能配置。与健康对照组中获得了同样的措施相比，配置文件，是用于诊断目的。目前，我们正在测试为ALS的诊断和预测疾病进展率，这些措施的敏感性和特异性。从长远来看，预计这项工作的延髓的ALS更精致endophenotype加强今后的努力，以确定ALS的基因位点和提高作为​​一个整体的疾病的诊断和治疗特异性。客观的评估，在此视频中演示可用于评估的讲话电机损伤的范围很广，包括中风，颅脑损伤，多发性硬化症，帕金森病有关的。

Watch this Scientific Journal Video about A Protocol for Comprehensive Assessment of Bulbar Dysfunction in Amyotrophic Lateral Sclerosis ALS at JoVE.com

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

评估，支持语音的生理机制的客观需要，以监测疾病的发病和进展与ALS的人，并量化在临床试验中的治疗效果。在这段视频中，我们提出了量化，在临床人群的讲话电机性能全面，仪器仪表为基础的协议。

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 ...

a-protocol-for-comprehensive-assessment-bulbar-dysfunction

Research

JoVE Journal

Medicine

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

33.9K 次观看.  University of Toronto. 评估，支持语音的生理机制的客观需要，以监测疾病的发病和进展与ALS的人，并量化在临床试验中的治疗效果。在这段视频中，我们提出了量化，在临床人群的讲话电机性能全面，仪器仪表为基础的协议。

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

Intraspinal Cell Transplantation for Targeting Cervical Ventral Horn in Amyotrophic Lateral Sclerosis and Traumatic Spinal Cord Injury

Respiratory compromise due to phrenic motor neuron loss is a debilitating consequence of a large proportion of human traumatic spinal cord injury (SCI) cases 1 and is the ultimate cause of death in patients with the motor neuron disorder, amyotrophic laterals sclerosis (ALS) 2.
ALS is a devastating neurological disorder that is characterized by relatively rapid degeneration of upper and lower motor neurons. Patients ultimately succumb to the disease on average 2-5 years following diagnosis because of respiratory paralysis due to loss of phrenic motor neuron innnervation of the diaphragm 3. The vast majority of cases are sporadic, while 10% are of the familial form. Approximately twenty percent of familial cases are linked to various point mutations in the Cu/Zn superoxide dismutase 1 (SOD1) gene on chromosome 21 4. Transgenic mice 4,5 and rats 6 carrying mutant human SOD1 genes (G93A, G37R, G86R, G85R) have been generated, and, despite the existence of other animal models of motor neuron loss, are currently the most highly used models of the disease.
Spinal cord injury (SCI) is a heterogeneous set of conditions resulting from physical trauma to the spinal cord, with functional outcome varying according to the type, location and severity of the injury 7. Nevertheless, approximately half of human SCI cases affect cervical regions, resulting in debilitating respiratory dysfunction due to phrenic motor neuron loss and injury to descending bulbospinal respiratory axons 1. A number of animal models of SCI have been developed, with the most commonly used and clinically-relevant being the contusion 8.
Transplantation of various classes of neural precursor cells (NPCs) is a promising therapeutic strategy for treatment of traumatic CNS injuries and neurodegeneration, including ALS and SCI, because of the ability to replace lost or dysfunctional CNS cell types, provide neuroprotection, and deliver gene factors of interest 9.
Animal models of both ALS and SCI can model many clinically-relevant aspects of these diseases, including phrenic motor neuron loss and consequent respiratory compromise 10,11. In order to evaluate the efficacy of NPC-based strategies on respiratory function in these animal models of ALS and SCI, cellular interventions must be specifically directed to regions containing therapeutically relevant targets such as phrenic motor neurons. We provide a detailed protocol for multi-segmental, intraspinal transplantation of NPCs into the cervical spinal cord ventral gray matter of neurodegenerative models such as SOD1G93A mice and rats, as well as spinal cord injured rats and mice 11.

Neural precursor transplantation is a promising strategy for protecting and/or replacing lost/dysfunctional cervical phrenic motor neurons in spinal cord injury (SCI) and the motor neuron disorder, amyotrophic laterals sclerosis (ALS). We provide a protocol for cell delivery to cervical spinal cord ventral horn in rodent models of ALS and SCI.

椎管内针对肌萎缩性脊髓侧索硬化症和外伤性脊髓损伤颈腹角细胞移植

Respiratory compromise due to phrenic motor neuron loss is a debilitating consequence of a large proportion of human traumatic spinal cord injury (SCI) ...

科研

医学

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 ...

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

The split hand phenomenon refers to predominant wasting of thenar muscles and is an early and specific feature of amyotrophic lateral sclerosis (ALS). A novel split hand index (SI) was developed to quantify the split hand phenomenon, and its diagnostic utility was assessed in ALS patients. The split hand index was derived by dividing the product of the compound muscle action potential (CMAP) amplitude recorded over the abductor pollicis brevis and first dorsal interosseous muscles by the CMAP amplitude recorded over the abductor digiti minimi muscle. In order to assess the diagnostic utility of the split hand index, ALS patients were prospectively assessed and their results were compared to neuromuscular disorder patients. The split hand index was significantly reduced in ALS when compared to neuromuscular disorder patients (P&#60;0.0001). Limb-onset ALS patients exhibited the greatest reduction in the split&#160;hand index, and a value of 5.2 or less reliably differentiated ALS from other neuromuscular disorders. Consequently, the split&#160;hand index appears to be a novel diagnostic biomarker for ALS, perhaps facilitating an earlier diagnosis.

Dissociated atrophy of intrinsic hand muscles, termed the split hand, appears to be a specific feature of amyotrophic lateral sclerosis (ALS).&#160;Consequently, a novel neurodiagnostic test, termed the split hand&#160;index, was developed to quantify the clinical phenomenon of the split hand, which differentiated ALS from mimic disorders.

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 ...

The Multiple Sclerosis Performance Test (MSPT): An iPad-Based Disability Assessment Tool

Precise measurement of neurological and neuropsychological impairment and disability in multiple sclerosis is challenging. We report a new test, the Multiple Sclerosis Performance Test (MSPT), which represents a new approach to quantifying MS related disability. The MSPT takes advantage of advances in computer technology, information technology, biomechanics, and clinical measurement science. The resulting MSPT represents a computer-based platform for precise, valid measurement of MS severity. Based on, but extending the Multiple Sclerosis Functional Composite (MSFC), the MSPT provides precise, quantitative data on walking speed, balance, manual dexterity, visual function, and cognitive processing speed. The MSPT was tested by 51 MS patients and 49 healthy controls (HC). MSPT scores were highly reproducible, correlated strongly with technician-administered test scores, discriminated MS from HC and severe from mild MS, and correlated with patient reported outcomes. Measures of reliability, sensitivity, and clinical meaning for MSPT scores were favorable compared with technician-based testing. The MSPT is a potentially transformative approach for collecting MS disability outcome data for patient care and research. Because the testing is computer-based, test performance can be analyzed in traditional or novel ways and data can be directly entered into research or clinical databases. The MSPT could be widely disseminated to clinicians in practice settings who are not connected to clinical trial performance sites or who are practicing in rural settings, drastically improving access to clinical trials for clinicians and patients. The MSPT could be adapted to out of clinic settings, like the patient&#8217;s home, thereby providing more meaningful real world data. The MSPT represents a new paradigm for neuroperformance testing. This method could have the same transformative effect on clinical care and research in MS as standardized computer-adapted testing has had in the education field, with clear potential to accelerate progress in clinical care and research.

The Multiple Sclerosis Performance Test MSPT: An iPad-Based Disability Assessment Tool

Precise measurement of neurological and neuropsychological impairment and disability in multiple sclerosis is challenging. We report methodologic details on a new test, the Multiple Sclerosis Performance Test (MSPT). This new approach to the objective of quantification of MS related disability provides a computer-based platform for precise, valid measurement of MS severity.

多发性硬化症性能测试（MSPT）：一个iPad为基础的残疾评估工具

Precise measurement of neurological and neuropsychological impairment and disability in multiple sclerosis is challenging. We report a new test, the ...

A Method of Trigonometric Modelling of Seasonal Variation Demonstrated with Multiple Sclerosis Relapse Data

This report describes a novel Stata-based application of trigonometric regression modelling to 55 years of multiple sclerosis relapse data from 46 clinical centers across 20 countries located in both hemispheres. Central to the success of this method was the strategic use of plot analysis to guide and corroborate the statistical regression modelling. Initial plot analysis was necessary for establishing realistic hypotheses regarding the presence and structural form of seasonal and latitudinal influences on relapse probability and then testing the performance of the resultant models. Trigonometric regression was then necessary to quantify these relationships, adjust for important confounders and provide a measure of certainty as to how plausible these associations were. Synchronization of graphing techniques with regression modelling permitted a systematic refinement of models until best-fit convergence was achieved, enabling novel inferences to be made regarding the independent influence of both season and latitude in predicting relapse onset timing in MS. These methods have the potential for application across other complex disease and epidemiological phenomena suspected or known to vary systematically with season and/or geographic location.

Combining plot analysis with trigonometric regression is a robust method for exploring complex, cyclical phenomena such as relapse onset timing in multiple sclerosis (MS). This method enabled unbiased characterisation of seasonal trends in relapse onset permitting novel inferences around the influence of seasonal variation, ultraviolet radiation (UVR) and latitude.

季节变化的三角建模的方法证明与多发性硬化症复发数据

This report describes a novel Stata-based application of trigonometric regression modelling to  55 years of multiple sclerosis relapse data from 46 ...

A Quick Phenotypic Neurological Scoring System for Evaluating Disease Progression in the SOD1-G93A Mouse Model of ALS

The SOD1-G93A transgenic mouse is the most widely used animal model of amyotrophic lateral sclerosis (ALS). At ALS TDI we developed a phenotypic screening protocol, demonstrated in video herein, which reliably assesses the neuromuscular function of SOD1-G93A mice in a quick manner. This protocol encompasses a simple neurological scoring system (NeuroScore) designed to assess hindlimb function. NeuroScore is focused on hindlimb function because hindlimb deficits are the earliest reported neurological sign of disease in SOD1-G93A mice. The protocol developed by ALS TDI provides an unbiased assessment of onset of paresis (slight or partial paralysis), progression and severity of paralysis and it is sensitive enough to identify drug-induced changes in disease progression. In this report, the combination of a detailed manuscript with video minimizes scoring ambiguities and inter-experimenter variability thus allowing for the protocol to be adopted by other laboratories and enabling comparisons between studies taking place at different settings. We believe that this video protocol can serve as an excellent training tool for present and future ALS researchers.

This video protocol describes a sensitive, reliable, and quick method for evaluating the neuromuscular deficits in a transgenic mouse model of amyotrophic lateral sclerosis.

一个快速的表型神经评分系统在ALS的SOD1-G93A小鼠模型评估疾病进展

The SOD1-G93A transgenic mouse is the most widely used animal model of amyotrophic lateral sclerosis (ALS). At ALS TDI we developed a phenotypic screening ...

A Protocol for the Use of Remotely-Supervised Transcranial Direct Current Stimulation (tDCS) in Multiple Sclerosis (MS)

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that uses low amplitude direct currents to alter cortical excitability. With well-established safety and tolerability, tDCS has been found to have the potential to ameliorate symptoms such as depression and pain in a range of conditions as well as to enhance outcomes of cognitive and physical training. However, effects are cumulative, requiring treatments that can span weeks or months and frequent, repeated visits to the clinic. The cost in terms of time and travel is often prohibitive for many participants, and ultimately limits real-world access. 
Following guidelines for remote tDCS application, we propose a protocol that would allow remote (in-home) participation that uses specially-designed devices for supervised use with materials modified for patient use, and real-time monitoring through a telemedicine video conferencing platform. We have developed structured training procedures and clear, detailed instructional materials to allow for self- or proxy-administration while supervised remotely in real-time. The protocol is designed to have a series of checkpoints, addressing attendance and tolerability of the session, to be met in order to continue to the next step. The feasibility of this protocol was then piloted for clinical use in an open label study of remotely-supervised tDCS in multiple sclerosis (MS). This protocol can be widely used for clinical study of tDCS.

A Protocol for the Use of Remotely-Supervised Transcranial Direct Current Stimulation tDCS in Multiple Sclerosis MS

The goal of this pilot study is to describe a protocol for the remotely-supervised delivery of transcranial direct current stimulation (tDCS) so that the procedure maintains standards of in-clinic practice, including safety, reproducibility, and tolerability. The feasibility of this protocol was tested in participants with multiple sclerosis (MS).

一个协议，用于远程监督经颅直流电刺激（TDCS）在多发性硬化症的使用（MS）

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that uses low amplitude direct currents to alter cortical ...

Robotic Lateral Pancreaticojejunostomy for Chronic Pancreatitis

Lateral pancreaticojejunostomy (LPJ) has shown good postoperative outcomes in patients with painful, morphine dependent, chronic pancreatitis (CP). The recent rise of robotic and laparoscopic pancreatic surgery has found benefits such as reduced time to functional recovery. Few studies have reported on the feasibility, technique and outcome of robotic LPJ, especially including transection of the gastroduodenal artery. The present study describes the main steps for robotic LPJ in a patient with painful chronic pancreatitis with a dilated main pancreatic duct. The patient underwent robotic LPJ. The LPJ anastomosis is performed using a running suture technique in a longitudinal side-to-side manner. Routinely, the gastroduodenal artery is transected to drain the entire length of the main pancreatic duct. The patient is in French position; 7 trocars are placed (4 robotic, 2 laparoscopic assistants, 1 liver-retractor). After docking of the robot system, the omental bursa is opened, and the right gastroepiploic artery and vein are ligated at their base at the lower border of the pancreas. Intraoperative ultrasonography is performed in order to determine trajectory of the dilated main pancreatic duct which is opened for its entire length after the gastroduodenal artery has been suture ligated both cranially and caudally from the main pancreatic duct. A Roux limb is created, and a latero-lateral PJ is fashioned using several 3-0 barbed sutures. A stapled jejuno-jejunostomy is created at sufficient distance from the pancreatic anastomosis, aided by a 50 cm suture. The described technique for robotic LPJ is a complex but feasible operation for patients with treatment refractory CP and a dilated main pancreatic duct. Due to its complexity, implementation in high volume centers with extensive experience with CP surgery may improve outcomes.

Robotic lateral pancreaticojejunostomy (RLPJ) may be used in patients with painful, morphine dependent, chronic pancreatitis and a dilated main pancreatic duct. We describe a standardized and reproducible technique for RLPJ, which includes transection of the gastroduodenal artery.

慢性胰腺炎的机器人侧胰腺肌切除术

Lateral pancreaticojejunostomy (LPJ) has shown good postoperative outcomes in patients with painful, morphine dependent, chronic pancreatitis (CP). The ...

Using a Chemical Biopsy for Graft Quality Assessment

Kidney transplantation is a life-saving treatment for a large number of people with end-stage renal dysfunction worldwide. The procedure is associated with an increased survival rate and greater quality of patient&#8217;s life when compared to conventional dialysis. Regrettably, transplantology suffers from a lack of reliable methods for organ quality assessment. Standard diagnostic techniques are limited to macroscopic appearance inspection or invasive tissue biopsy, which do not provide comprehensive information about the graft. The proposed protocol aims to introduce solid phase microextraction (SPME) as an ideal analytical method for comprehensive metabolomics and lipidomic analysis of all low molecular compounds present in kidneys allocated for transplantation. The small size of the SPME probe enables performance of a chemical biopsy, which enables extraction of metabolites directly from the organ without any tissue collection. The minimum invasiveness of the method permits execution of multiple analyses over time: directly after organ harvesting, during its preservation, and immediately after revascularization at the recipient&#8217;s body. It is hypothesized that the combination of this novel sampling method with a high-resolution mass spectrometer will allow for discrimination of a set of characteristic compounds that could serve as biological markers of graft quality and indicators of possible development of organ dysfunction.

The protocol presents utilization of the chemical biopsy approach followed by comprehensive metabolomic and lipidomic analysis for quality assessment of kidney grafts allocated for transplantation.

使用化学活检进行移植质量评估

Kidney transplantation is a life-saving treatment for a large number of people with end-stage renal dysfunction worldwide. The procedure is associated ...

Magnetic Resonance Imaging of Multiple Sclerosis at 7.0 Tesla

The overall goal of this article is to demonstrate a state-of-the-art ultrahigh field (UHF) magnetic resonance (MR) protocol of the brain at 7.0 Tesla in multiple sclerosis (MS) patients. MS is a chronic inflammatory, demyelinating, neurodegenerative disease that is characterized by white and gray matter lesions. Detection of spatially and temporally disseminated T2-hyperintense lesions by the use of MRI at 1.5 T and 3 T represents a crucial diagnostic tool in clinical practice to establish accurate diagnosis of MS based on the current version of the 2017 McDonald criteria. However, the differentiation of MS lesions from brain white matter lesions of other origins can sometimes be challenging due to their resembling morphology at lower magnetic field strengths (typically 3 T). Ultrahigh field MR (UHF-MR) benefits from increased signal-to-noise ratio and enhanced spatial resolution, both key to superior imaging for more accurate and definitive diagnoses of subtle lesions. Hence, MRI at 7.0 T has shown encouraging results to overcome the challenges of MS differential diagnosis by providing MS-specific neuroimaging markers (e.g., central vein sign, hypointense rim structures and differentiation of MS grey matter lesions). These markers and others can be identified by other MR contrasts other than T1 and T2 (T2*, phase, diffusion) and substantially improve the differentiation of MS lesions from those occurring in other neuroinflammatory conditions such as neuromyelitis optica and Susac syndrome. In this article, we describe our current technical approach to study cerebral white and grey matter lesions in MS patients at 7.0 T using different MR acquisition methods. The up-to-date protocol includes the preparation of the MR setup including the radio-frequency coils customized for UHF-MR, standardized screening, safety and interview procedures with MS patients, patient positioning in the MR scanner and acquisition of dedicated brain scans tailored for examining MS.

Here, we present a protocol to acquire magnetic resonance (MR) images of multiple sclerosis (MS) patient brains at 7.0 Tesla. The protocol includes preparation of the setup including the radio-frequency coils, standardized interview procedures with MS patients, subject positioning in the MR scanner and MR data acquisition.

7.0特斯拉多发性硬化症的磁共振成像

The overall goal of this article is to demonstrate a state-of-the-art ultrahigh field (UHF) magnetic resonance (MR) protocol of the brain at 7.0 Tesla in ...