オーストラリアの運動ニューロン疾患研究所（MNDRIA）からの支援に資金を提供し、シルヴィアとチャールズビアテル慈善財団臨床研究者の助成金、Ramaciotti財団と国立保健オーストラリアの医学研究評議会（プロジェクト無償番号APP1024915）は感謝して承諾されます。

1。患者の準備<ol><li>プロスペクティブに連続した患者を募集。注：以下のプロトコルは、シドニー西部地域保健サービスヒューマン研究倫理委員会によって承認されています。インフォームドコンセントは、すべての患者から提供された。患者は、ウェストミード病院でALS /神経筋クリニックから将来に向かってと連続して採用された。 </li><li>テストのためのALS患者の適合性を判断。 ALSまたは神経筋障害と診断されていない患者を除外します。 </li><li>共存焦点神経障害、肘での手首や尺骨神経障害での中央値は神経障害の患者を除外します。 </li><li>例えば、糖尿病性多発神経障害のように一般性神経障害の患者を除外。 </li><li>広範囲に調査し、臨床的にフォローアップの患者を、ALSまたは神経筋模倣疾患の診断を確認する。 </li><li>インフォームドコンセントは、AlのためのALSおよび神経筋模倣障害患者を含め、すべての患者から提供されていることを確認L神経生理学的な手順。 </li></ol> 2。臨床的評価<ol><li>筋萎縮性側索硬化症機能評価尺度改訂版（ALSFRS-R）を使用して、すべてのALS患者の臨床病期を決定するには、18得点 。 </li><li>以前に報告された式に従って、すべてのALS患者における疾患進行の速度を決定する; 症状の（48-ALSFRS-R）/期間）19。 </li><li>医学研究評議会（MRC）評価スケール20を使用して、すべての患者の筋力を決定します。下肢（股関節屈曲、膝伸展、足関節背屈、総得点30）筋群上肢（;肘屈曲、肘の伸展、手首背屈、、指外転親指拉致、総得点60肩の外転）を含む、全MRCスコアを開発。筋力が正常であれば、総MRCスコアは90で​​なければなりません。 </li><li>すべてのALSにおける延髄や手足のように定義発病部位を決定患者。 </li></ol> 3。神経生理学的評価<ol><li>中央値での運動神経伝導検査を実施し、母指外転ブレビス（APB）、最初の背側骨間（FDI）と外転筋桁ミニミ（ADM）の筋肉から記録された複合筋活動電位（CMAP）応答と神経を尺骨。 </li><li>アルコールワイプの適用に続いて皮膚抵抗を低減させる研磨剤ゲルで皮膚表面を洗浄することにより、手首の刺激部位を準備する。最大CMAP応答（現在の最大上）を生成するために必要な強度を超える20％に刺激電流を設定します。 </li><li>選択した刺激部位が体積伝導が回避されるような刺激のための最も低い閾値を示すことを確認してください。 </li><li>アルコールの適用に続いて皮膚抵抗を低減させる研磨剤ゲル、ワイプで皮膚表面を洗浄することにより、各筋肉の上の​​記録部位を準備する。 </li><li>複合機ACTIのサイズを記録しますAPB、ADM、および直接投資の筋肉からの電位（CMAP）に。各筋肉の上腹腱配置に配置さ10ミリメートルゴールドディスク電極で記録される応答。参照電極は、親指の付け根の上に配置されるようにしながら、具体的には、、CMAP応答の負の離陸を確保し、それぞれの筋肉の中間点の上（APBと直接投資CMAPの録音を）活性電極を配置し、ADMのための数字5（のベースCMAP録音）。 </li><li> 5cmで8センチメートルのFDIまでの距離に、APBとADM化合モータ活動電位応答の刺激陰極と活性電極間の距離を設定します。 </li><li>アーティファクトを低減するために導電性ゲルを、電極を刺激するとG1の間、手の背側面に電気外科ニュートラルアース板を配置します。従来中性地球の適用にアルコールを塗布、続いて皮膚抵抗を低減させる研磨剤ゲル、ワイプで皮膚表面を洗浄することによってサイトを準備する。 </li><li>フィルタ設定が3Hzの（低域フィルタ）、10キロヘルツ（高周波フィルタ）との間にあることを確認します。 </li><li>掃引速度は20ミリ秒、または2ミリ秒/目盛りに設定されていることを確認してください。 </li><li>記録CMAP応答の感度は5 mVのに設定されていることを確認してください。 </li><li>研究を通して刺激部位の温度を監視し、手足の温度を32℃に維持されることを保証</li></ol> 4。分析と解釈<ol><li> ALS患者におけるAPB、直接投資とADM筋肉や神経筋模倣疾患対照にわたりベースライン·ツー·ピークのCMAP振幅（MV）を測定します。 </li><li>以下のように、APBと直接投資の筋肉の上に記録されたCMAP振幅を乗じ、とADMの筋肉の上に記録されたCMAP振幅により、本製品を分割することにより、スプリットハンド指数（ 図1）を計算します。 SI = APB CMAP * FDI CMAP _________________________ ＆＃160; ADM CMAP </li><li>診断精度（STARD）基準の報告のための基準に従って、ALS患者や神経筋模倣性障害の病理学的コントロールの間のSI値を比較することにより、スプリットハンド指数の診断ユーティリティを決定します。 </li><li>特性（ROC）曲線を操作して受信機を使用して、スプリットハンド·インデックスに最適な診断のカットオフ値を決定します。 ALSおよび神経筋疾患患者由来のSI値の感度（y軸）および1 - specificty（x軸）をプロットすることによってROC曲線を導出する。 </li></ol>

<ol>
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著者らは、開示することは何もありません。

本研究では、ALSの新規神経生理学的な診断バイオマーカーでのスプリットハンド指数の診断ユーティリティについて報告します。 SIは確実に5.2の最適診断カットオフ値は、神経筋疾患のALSを区別した。 SIの減少は、四肢に発症ALS患者で最も顕著であった。重要なのは、最近開発された診断基準11に従って、診断「可能」カテゴリーに分類されたALS患者のかなりの割合が、異常なSIを示?...

スプリットハンドは 、小指の筋肉が相対的に維持されながらも、本来の手の筋肉の母指球の複雑なグループ[母指外転·ブレビス（APB）と第背側骨間（FDI）]の優先的な萎縮を意味し、筋萎縮性の特異的かつ早期の臨床機能です側索硬化症（ALS）1-4。スプリットハンドサインは、ALSに特異的であるという知見は、ALSの3診断バイオマーカーとしてのスプリット手の合図のための潜在的な役割を示唆している。 スプリットハンドサインの定量化は、新たな神経生理学的バイオマーカーの開発を通じて、ALSの診断をさらに助けることがあります。具体的には、分割された手の現象を定量化するスプリットハンド指数（SI）は、化合物筋活動電位（CMAP）を乗算することによって導出される母指球複合体筋（APB及びFDI）上に記録され、CMAP振幅によってこの製品を分割振幅HYPにわたって記録othenar筋肉（すなわち外転小指、ADM）5。 ALSの診断は6に署名し、上下の運動ニューロンの組み合わせを網羅する、臨床的に基づく基準に大きく依存しています。これらの基準は、しかし、特に、疾患プロセス7-10の初期段階でALSの診断を確立する際に非感受性とみなされた。診断基準の最近の変更が11を開発し、これらの基準は、診断感度12月16日を増やすように見えますが、増加は感度が延髄発性ALS患者15に制限されそうです。 特徴的試験の非存在下では、ALSの診断は、有意に08遅延させることができる。最終的には、臨床試験に神経保護治療法と採用の制度は、おそらく重要な治療上のウィンドウ期間9、17を超えて、遅れる場合があります。その結果、SIの診断ユーティリティは、将来に向かって散発ALS患者で評価した。

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			<td style="width:136px;"></td>
			<td style="width:203px;"></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Abrasive gel (Nu Prep)</td>
			<td>Weaver and Company</td>
			<td>N-TA\/P\H-3 ENG</td>
			<td>Skin preperation</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;"></td>
			<td colspan="2">(www.doweaver.com)</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;"></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Alcohol wipe</td>
			<td>Triad Disposables</td>
			<td>103101</td>
			<td>Skin preperation</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;"></td>
			<td colspan="2">(www.triad-group.net)</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;"></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">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 height="20">
			<td height="20" style="height:20px;"></td>
			<td colspan="2">(www.doweaver.com)</td>
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			<td height="20" style="height:20px;"></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Amyotrophic lateral sclerosis rating scale-revised questionnaire</td>
			<td>Publication&#160;</td>
			<td>Experimental builder</td>
			<td>Stage disease</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;"></td>
			<td colspan="2">(see Methods and References)</td>
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			<td height="20" style="height:20px;">Medical Research Council muscle strength scale</td>
			<td>Medical Research Council-UK</td>
			<td>Experimental builder</td>
			<td>Stage disease</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;"></td>
			<td colspan="2">(see Methods and References)</td>
			<td></td>
		</tr>
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		<tr height="20">
			<td height="20" style="height:20px;"></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;"></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td colspan="2" height="20" style="height:20px;">Table of equipment used</td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Name of the equipment used</td>
			<td>Company</td>
			<td>Catalog number</td>
			<td>Comments</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;"></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Nerve conduction machine (Synergy/Nicolet EDX)</td>
			<td>CareFusion (www.carefusion.com/medical-products/neurology)</td>
			<td>SA110106M</td>
			<td>To measure split hand index</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;"></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Synergy software</td>
			<td>CareFusion</td>
			<td>765654679</td>
			<td>To measure split hand index</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;"></td>
			<td colspan="3">(www.carefusion.com/medical-products/neurology)</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;"></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Tem millimeter gold cup disc electrodes</td>
			<td>Grass Technologies</td>
			<td>F-E5GH-60</td>
			<td>To record motor responses</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;"></td>
			<td colspan="2">(www.grasstechnologies.com)</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;"></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Neural earth plate</td>
			<td>Westmead Hospital</td>
			<td>Experimental builder</td>
			<td>To record limb temperature</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;"></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">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

スプリットハンド現象は母指球筋肉の支配的な消耗を参照し、筋萎縮性側索硬化症（ALS）の初期及び具体的な機能です。新規分割ハンド指数（SI）は、分割ハンド現象を定量化するために開発され、その診断ユーティリティは、ALS患者において評価した。スプリットハンドインデックスは複合筋活動電位（CMAP）の積で除して得られたもの転小指の筋にわたって記録CMAP振幅による外転母指ブレビスと第背側骨間筋にわたって記録振幅。スプリットハンド指数の診断的有用性を評価するために、ALS患者は将来を見越して評価し、その結果を、神経筋疾患の患者と比較した。神経筋疾患患者（P &lt;0.0001）と比較した場合、分割ハンド指数は有意に減少したALS。四肢発性ALS患者は、分割手の指数の最大の減少、および値を示した5.2以下で確実に他の神経筋疾患のALSを分化した。従って、スプリットハンド指数は、おそらく早期診断を容易にする、ALSのための新規な診断バイオマーカーであると思われる。

臨床表現型 合計では、44 ALS患者は76％（N = 33）が可能な、ALSなどの明確な、または可能性が高く、かつ24％（N = 11）に分類された淡路基準11によると、そのうちの研究した。 ALSの診断は、鋭意研究し、最大3年間の臨床追跡後に「可能性」コホートで確認され、53％がこの期間中に死亡した。延髄発症型疾患ALS患者の59％での四肢に発症しながら、41％で明ら?...

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

内因性の手の筋肉の解離萎縮、スプリット手と呼ばれる筋萎縮性側索硬化症（ALS）の具体的な特徴であると思われる。その結果、新たなneurodiagnosticテストは、模倣障害にALSを区別スプリットハンドの臨床現象を定量化するために開発された、 分割された手のインデックスと呼ばれる。

筋萎縮性側索硬化症の診断で解離極限ハンド筋萎縮の有用性

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

Research

JoVE Journal

Medicine

31.2K ビュー.  Westmead Hospital. 内因性の手の筋肉の解離萎縮、スプリット手と呼ばれる筋萎縮性側索硬化症（ALS）の具体的な特徴であると思われる。その結果、新たなneurodiagnosticテストは、模倣障害にALSを区別スプリットハンドの臨床現象を定量化するために開発された、 分割された手のインデックスと呼ばれる。 

ビデオ: 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.

筋萎縮性側索硬化症における延髄機能障害の包括的評価（ALS）のためのプロトコル

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

医学

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.

筋萎縮性側索硬化症や外傷性脊髄損傷では頚椎前角をターゲットとするための髄腔内細胞移植

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

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.

臨床試験および筋萎縮性側索硬化症（ALS）のマウスモデルにおける脊髄の除去

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

Real-time Digital Imaging of Leukocyte-endothelial Interaction in Ischemia-reperfusion Injury (IRI) of the Rat Cremaster Muscle

Ischemia-reperfusion injury (IRI) has been implicated in a large array of pathological conditions such as cerebral stroke, myocardial infarction, intestinal ischemia as well as following transplant and cardiovascular surgery.1 Reperfusion of previously ischemic tissue, while essential for the prevention of irreversible tissue injury, elicits excessive inflammation of the affected tissue. Adjacent to the production of reactive oxygen species, activation of the complement system and increased microvascular permeability, the activation of leukocytes is one of the principle actors in the pathological cascade of inflammatory tissue damage during reperfusion.2, 3 Leukocyte activation is a multistep process consisting of rolling, firm adhesion and transmigration and is mediated by a complex interaction between adhesion molecules in response to chemoattractants such as complement factors, chemokines, or platelet-activating factor.4
While leukocyte rolling in postcapillary venules is predominantly mediated by the interaction of selectins5 with their counter ligands, firm adhesion of leukocytes to the endothelium is selectin-controlled via binding to intercellular adhesion molecules (ICAM) and vascular cellular adhesion molecules (VCAM).6, 7 
Gold standard for the in vivo observation of leukocyte-endothelial interaction is the technique of intravital microscopy, first described in 1968.8
Though various models of IRI (ischemia-reperfusion injury) have been described for various organs, 9-12 only few are suitable for direct visualization of leukocyte recruitment in the microvascular bed on a high level of image quality.8 
We here promote the digital intravital epifluorescence microscopy of the postcapillary venule in the cremasteric microcirculation of the rat 13 as a convenient method to qualitatively and quantitatively analyze leukocyte recruitment for IRI-research in striated muscle tissue and provide a detailed manual for accomplishing the technique. We further illustrate common pitfalls and provide useful tips which should enable the reader to truly appreciate, and safely perform the method.
In a step by step protocol we depict how to get started with respiration controlled anesthesia under sufficient monitoring to keep the animal firmly anesthetized for longer periods of time. We then describe the cremasteric preparation as a thin flat sheet for outstanding optical resolution and provide a protocol for leukocyte imaging in IRI that has been well established in our laboratories.

Real-time Digital Imaging of Leukocyte-endothelial Interaction in Ischemia-reperfusion Injury IRI of the Rat Cremaster Muscle

Digital intravital epifluorescence microscopy of postcapillary venules in the cremasteric microcirculation is a convenient method to gain insights into leukocyte-endothelial interaction in vivo in ischemia-reperfusion injury (IRI) of striated muscle tissue. We here provide a detailed protocol to safely perform the technique and discuss its applications and limitations.

ラットの精巣挙筋の虚血再灌流障害における白血球 - 内皮相互作用のリアルタイムデジタルイメージング（IRI）

Ischemia-reperfusion injury (IRI) has been implicated in a large array of pathological conditions such as cerebral stroke, myocardial infarction, ...

Tibial Nerve Transection - A Standardized Model for Denervation-induced Skeletal Muscle Atrophy in Mice

The tibial nerve transection model is a well-tolerated, validated, and reproducible model of denervation-induced skeletal muscle atrophy in rodents. Although originally developed and used extensively in the rat due to its larger size, the tibial nerve in mice is big enough that it can be easily manipulated with either crush or transection, leaving the peroneal and sural nerve branches of the sciatic nerve intact and thereby preserving their target muscles. Thus, this model offers the advantages of inducing less morbidity and impediment of ambulation than the sciatic nerve transection model and also allows investigators to study the physiologic, cellular and molecular biologic mechanisms regulating the process of muscle atrophy in genetically engineered mice. The tibial nerve supplies the gastrocnemius, soleus and plantaris muscles, so its transection permits the study of denervated skeletal muscle composed of fast twitch type II fibers and/or slow twitch type I fibers. Here we demonstrate the tibial nerve transection model in the C57Black6 mouse. We assess the atrophy of the gastrocnemius muscle, as a representative muscle, at 1, 2, and 4 weeks post-denervation by measuring muscle weights and fiber type specific cross-sectional area on paraffin-embedded histologic sections immunostained for fast twitch myosin.

The tibial nerve transection model is a well-tolerated, validated, and reproducible model of skeletal muscle atrophy. The model surgical protocol is described and demonstrated in C57Black6 mice. &#160;

脛骨神経切断 - マウスにおける脱神経誘発性骨格筋萎縮のために標準化されたモデル

The tibial nerve transection model is a well-tolerated, validated, and reproducible model of denervation-induced skeletal muscle atrophy in rodents. ...

High-throughput Flow Cytometry Cell-based Assay to Detect Antibodies to N-Methyl-D-aspartate Receptor or Dopamine-2 Receptor in Human Serum

Over the recent years, antibodies against surface and conformational proteins involved in neurotransmission have been detected in autoimmune CNS diseases in children and adults. These antibodies have been used to guide diagnosis and treatment. Cell-based assays have improved the detection of antibodies in patient serum. They are based on the surface expression of brain antigens on eukaryotic cells, which are then incubated with diluted patient sera followed by fluorochrome-conjugated secondary antibodies. After washing, secondary antibody binding is then analyzed by flow cytometry. Our group has developed a high-throughput flow cytometry live cell-based assay to reliably detect antibodies against specific neurotransmitter receptors. This flow cytometry method is straight forward, quantitative, efficient, and the use of a high-throughput sampler system allows for large patient cohorts to be easily assayed in a short space of time. Additionally, this cell-based assay can be easily adapted to detect antibodies to many different antigenic targets, both from the central nervous system and periphery. Discovering additional novel antibody biomarkers will enable prompt and accurate diagnosis and improve treatment of immune-mediated disorders.

Over the recent years, live cell-based assays have been used successfully to detect antibodies against surface and conformational antigens. Here, we describe a method using high-throughput flow cytometry enabling the analysis of large cohorts of patients. Detection of novel antibodies will improve diagnosis and treatment of immune-mediated disorders.

ハイスループットフローサイトメトリー細胞ベースのアッセイN-メチル-D-アスパラギン酸受容体またはヒト血清中のドーパ​​ミン-2受容体に対する抗体を検出する

Over the recent years, antibodies against surface and conformational proteins involved in neurotransmission have been detected in autoimmune CNS diseases ...

Ischemic Tissue Injury in the Dorsal Skinfold Chamber of the Mouse: A Skin Flap Model to Investigate Acute Persistent Ischemia

Despite profound expertise and advanced surgical techniques, ischemia-induced complications ranging from wound breakdown to extensive tissue necrosis are still occurring, particularly in reconstructive flap surgery. Multiple experimental flap models have been developed to analyze underlying causes and mechanisms and to investigate treatment strategies to prevent ischemic complications. The limiting factor of most models is the lacking possibility to directly and repetitively visualize microvascular architecture and hemodynamics. The goal of the protocol was to present a well-established mouse model affiliating these before mentioned lacking elements. Harder et al. have developed a model of a musculocutaneous flap with a random perfusion pattern that undergoes acute persistent ischemia and results in ~50% necrosis after 10 days if kept untreated. With the aid of intravital epi-fluorescence microscopy, this chamber model allows repetitive visualization of morphology and hemodynamics in different regions of interest over time. Associated processes such as apoptosis, inflammation, microvascular leakage and angiogenesis can be investigated and correlated to immunohistochemical and molecular protein assays. To date, the model has proven feasibility and reproducibility in several published experimental studies investigating the effect of pre-, peri- and postconditioning of ischemically challenged tissue.

The window of the murine dorsal skinfold chamber presented visualizes a zone of acute persistent ischemia of a musculocutaneous flap. Intravital epi-fluorescence microscopy permits for direct and repetitive assessment of the microvasculature and quantification of hemodynamics. Morphologic and hemodynamic results can further be correlated with histological and molecular analyses.

マウスの背部皮脂商工における虚血性組織損傷：皮膚弁モデル急性永続虚血を調査する

Despite profound expertise and advanced surgical techniques, ischemia-induced complications ranging from wound breakdown to extensive tissue necrosis are ...

Single-stage Dynamic Reanimation of the Smile in Irreversible Facial Paralysis by Free Functional Muscle Transfer

Unilateral facial paralysis is a common disease that is associated with significant functional, aesthetic and psychological issues. Though idiopathic facial paralysis (Bell&#8217;s palsy) is the most common diagnosis, patients can also present with a history of physical trauma, infectious disease, tumor, or iatrogenic facial paralysis. Early repair within one year of injury can be achieved by direct nerve repair, cross-face nerve grafting or regional nerve transfer. It is due to muscle atrophy that in long lasting facial paralysis complex reconstructive methods have to be applied. Instead of one single procedure, different surgical approaches have to be considered to alleviate the various components of the paralysis.
The reconstruction of a spontaneous dynamic smile with a symmetric resting tone is a crucial factor to overcome the functional deficits and the social handicap that are associated with facial paralysis. Although numerous surgical techniques have been described, a two-stage approach with an initial cross-facial nerve grafting followed by a free functional muscle transfer is most frequently applied. In selected patients however, a single-stage reconstruction using the motor nerve to the masseter as donor nerve is superior to a two-stage repair. The gracilis muscle is most commonly used for reconstruction, as it presents with a constant anatomy, a simple dissection and minimal donor site morbidity.
Here we demonstrate the pre-operative work-up, the post-operative management, and precisely describe the surgical procedure of single-stage microsurgical reconstruction of the smile by free functional gracilis muscle transfer in a step by step protocol. We further illustrate common pitfalls and provide useful tips which should enable the reader to truly comprehend the procedure. We further discuss indications and limitations of the technique and demonstrate representative results.

The use of the masseteric nerve as donor nerve represents a single-stage alternative to the criterion standard two-stage procedure of cross-facial nerve grafting and free muscle transfer in facial paralysis. We provide a detailed description to safely perform this technique with a gracilis muscle transfer and discuss indications and limitations.

フリー機能性筋肉転送により不可逆顔面神経麻痺が笑うの単段ダイナミック蘇生

Unilateral facial paralysis is a common disease that is associated with significant functional, aesthetic and psychological issues. Though idiopathic ...

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.

多発性硬化症の再発のデータを用いて実証季節変動の三角モデリングの方法

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

Design, Fabrication, and Administration of the Hand Active Sensation Test (HASTe)

The concept of personalizing neurologic rehabilitation, based on individual impairments, has experienced a recent surge. In parallel, the number of outcome measures of upper extremity motor performance has grown. However, clinicians and researchers lack practical, quantitative measures of the hand&#8217;s natural role as a receptor of the environment. The Hand Active Sensation Test (HASTe), developed by Williams and colleagues in 2006, is a valid and reliable measure of haptic performance. Though not available commercially, the HASTe can be fabricated from inexpensive materials, and it has been used successfully to identify impairments in haptic touch in individuals with stroke. (Williams, 2006). This paper presents the methods of design and fabrication of the HASTe testing kit, as well as a visual screen to be used during administration, and instructions for the tests administration and scoring.

Design, Fabrication, and Administration of the Hand Active Sensation Test HASTe

The Hand Active Sensation Test (HASTe) is a valid and reliable measure of haptic performance, which has been used successfully to identify impaired haptic touch in individuals with stroke. The purpose of this paper is to describe the design, fabrication and administration of the HASTe.

ハンドアクティブ感覚テスト（ヘイスト）の設計、製造、および管理

The concept of personalizing neurologic rehabilitation, based on individual impairments, has experienced a recent surge. In parallel, the number of ...