We thank the patients who gave their consent and contributed to the publication.

ここでは、技術的に神経嚥下障害を有する患者における流涎症の治療のために使用される方法を記載します。我々は以前7公開されている有効性の結果、に焦点を当てることはありません。本論文では、結果のセクションでは、我々は、これらの患者は、ボツリヌス毒素で構成され、全人口の代表、と考えられている2014年から2016年に扱わ長期フォローアップと連続して5人の患者（3治療セッション）からのデータを提示しますサンルイジ・ゴンザーガ病院のサービス。プロトコルが承認され、人体実験上のローカル倫理基準委員会のガイドラインに従いました。 1.患者の募集注：このアプローチの対象患者は、大人のような抗コリン薬などの薬理学的治療への障害や禁忌の歴史を持つ神経学的嚥下障害への二次重度の流涎症に中等度に苦しんでいます。 <ol><li>患者はEXPによって評価されていることを確認BoNT注入前と流涎症の重症度と頻度がよだれ頻度および重症度スケール（DFSS）14で評価されるerienced神経科医。 注：DFSSスコアは（4 =常に1 =決して、2 =時折/ない毎日、その日の3 =頻繁/一部、）周波数の和と重症度（1 = droolsがありません、のみ2 =軽度またはであります4 =重度またはよだれ3 =中等度または唇とあごに湿った湿った唇は、サブスコア14）、手、トレイを、湿潤5 =おびただしいや衣服衣服に延びており、濡れたオブジェクト。サブスコアの両方におけるスコア&gt; 2は、資格のカットオフとして使用されます。 注：患者および/または介護者が提供する客観的かつ既往のデータに基づいて、神経学者のスコアスケール。また、視覚的アナログ尺度（VAS）は、流涎症に関連する患者の主観的苦痛の評価のために投与しなければなりません。 VASは、と10センチメートル水平線によって表される自己報告尺度であります患者の不快感の一方の端を表す各終わりにtatement（0 = &quot;極度の不快感」への100から=&quot;違和感のありません」）。 </li><li>治療の有効性を評価するための便利なツール（ 図1）のように、のBoNT注射の前に唾液アスピレーター（該当する場合）を介して、毎日唾液願望の数を収集します。 </li><li> 3と6ヶ月の治療後のフォローアップ、1、中にDFSS、毎日の唾液誤嚥性評価と一緒に神経学的評価を繰り返し、または流涎症の再発によると。毎日の願望の数は1ヶ月のフォローアップ評価に比べて50％以上増加すると特に、再治療が考慮されなければなりません。 </li><li>注射直後手順有害事象（局所疼痛、局所出血、および顔面神経麻痺）を収集します。フォローアップ評価時の治療の有害事象（局所疼痛、顔面神経麻痺、咀嚼弱さ、粘性唾液、口渇）を収集します。 </li></ol> 2.手順<ol><li> BoNT-準備 注：abobotulinumtoxinAは、ボツリヌス菌複合体ヘマグルチニンのA型ボツリヌス毒素です。それは、筋肉内または皮下注射用溶液のための粉末です。 <ol><li>成人の流涎症の治療のための、abobotulinumtoxinAの250 IU / mLを含む溶液を得るために、注射用の0.9％塩化ナトリウム溶液2mLで500 IU abobotulinumtoxinAを再構成します。 </li><li>各顎下腺では50 IUと75 IUをそれぞれの耳下腺に次のように患者あたりabobotulinumtoxinAの250 IUの合計を管理します。このように、薬剤浪費を避けるために、単一バイアルで2人の患者を治療します。 </li></ol></li><li>患者の準備<ol><li>手順のと治療の潜在的なリスクと利益の適切な説明の後、患者から書面によるインフォームドコンセントを得ます。 </li><li>超音波テーブルの上に患者を配置首と仰臥位と可能性を拡張します。 注：いないすべての神経学的状態は、首の完全な拡張を可能に流涎症につながることを考えてみましょう。 </li><li>耳下腺および防腐と顎下腺上の領域で皮膚を消毒します。エチレンクロリドスプレーで各皮膚のアクセス部位を麻酔。 </li></ol></li><li>超音波誘導 注：線形変換器と超音波ガイド下の手順（5から10 MHzの）は、リアルタイムの筋肉、腺、より大きな血管または唾液管の可視化、および他の周囲の構造を得るためには、同様の腺のローカライズに使用されます腺組織内の正しい針位置。 <ol><li>超音波システムの電源をオンにし、試験を開始し、「開始 - 終了」ボタンを押してください。 </li><li> （ - 10 MHzの5）高周波プローブを選択するために、「プローブ」ボタンを押してください。 </li><li> 「患者」ボタンを押して、患者の名前とsurnaを挿入私。 </li><li> （：「小さな組織」、サブプロトコル：「一般」、 すなわち 、プロトコル）適切なプロトコルおよびサブプロトコルを選択するには、「プロトコル」ボタンを押してください。 </li><li> 「深」ボタンを押してから5 cmのビューの深さを指定します。 </li><li> 2センチメートルの最大の詳細を選択するために「フォーカス」ボタンを押してください。 </li><li>周囲の組織に比べて均質echotextureと低エコー領域として表示される顎下腺を、可視化するために、二腹筋の前部および後部の腹の間に、下顎の下にトランスデューサーを配置します。 注：理想的には2つの象限、1頭側と1尾に分かれ顎下腺を考えてみましょう。横針アクセスのための最も広いグランド径を特定します。 </li><li>周囲の組織に比べて均質echotextureと低エコー領域として表示されます耳下腺を、可視化するために外耳道以下トランスデューサを配置します。 NOTE：理想的には4つの象限、2頭側と2尾に分かれ耳下腺を考えてみましょう。外耳道および下顎角、頭蓋部分に1つ、腺（ 補足図 ）の尾の部分で1間の噴射途中のための2つのアクセス部位を特定します。 </li></ol></li><li> BoNT注射 注：変換器から針貫通少なくとも0.5 CMに、注射用22 G針を使用してください。針が明るい反響行として表示されるように、変換器は、針に長手方向に配向されなければなりません。針の先端は、神経血管構造の損傷を防止する、目標に向かって進むように、このようにして、軟組織への針の侵入は、処置中に監視することができます。 <ol><li>顎下腺へのアクセスに最も広い腺径で横型短アクセスアプローチを使用します。 </li><li>上部の顎下の象限に25 IUのBoNT-Aを注入します。注入後、少しねを撤回各顎下腺に50 IUの合計25 IUのBoNT-Aを注入し、下顎下の象限に向かって針先の方向をedleと変更。 注：このようにして、2つの顎下領域（頭蓋および尾）は腺組織内の薬剤の広範な拡散を提供し、注入されます。 </li><li>耳下腺注入のための2つのアクセス部位を使用してください。 2は、外耳道および下顎角、腺の頭蓋部分に1つ、腺の尾の部分における1の中間にアクセスし確認します。 </li><li>内側頭蓋象限に19 IUのBoNT-A - （腺の頭蓋部分的に）上位アクセスを使用して、18を注入します。注入後、わずか腺の頭蓋一部のサイトを離れることなく、針を撤回し、横方向の頭蓋象限に向かって針の先端の向きを変えます。 19 IUのBoNT-A - 18を注入します。 </li><li> 19のBoNT-IU - （腺の尾の部分で）下のアクセスを使用して、18を注入中央 - 尾側の象限に。注入後、わずか腺の尾の部分のサイトを離れることなく、針を撤回し、横尾側象限に向かって針の先端の向きを変えます。 19 IUのBoNT-A - 18を注入します。 注：このように、4耳下腺の領域（内側 - 頭蓋、横頭蓋、内側 - 尾側と横尾）は腺組織内の薬剤の広範な拡散を提供する、75 IUのBoNT-Aの合計を注射します。 </li><li> 2分 - 各注入の後、任意の1のために、滅菌ガーゼで出血を軽くたたきます。任意の潜在的な有害事象のために1時間後の患者を再評価。痛みを永続化する場合には、非ステロイド性抗炎症薬を投与します。 1ヶ月後のフォローアップ検査をスケジュールします。 </li></ol></li></ol>

<ol>
	<li>Kumar, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Swallowing+and+dysphagia+in+neurological+disorders.">Swallowing and dysphagia in neurological disorders.</a> Rev Neurol Dis. 7 (1), 19-27 (2010).</li><li>Lakraj, A. A., Moghimi, N., Jabbari, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sialorrhea:+anatomy,+pathophysiology+and+treatment+with+emphasis+on+the+role+of+botulinum+toxins.">Sialorrhea: anatomy, pathophysiology and treatment with emphasis on the role of botulinum toxins.</a> Toxins (Basel). 5 (5), 1010-1031 (2013).</li><li>Reed, J., Mans, C. K., Brietzke, S. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Surgical+management+of+drooling:+a+meta-analysis.">Surgical management of drooling: a meta-analysis.</a> Arch Otolaryngol Head Neck Surg. 135 (9), 924-931 (2009).</li><li>Crysdale, W. S., White, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Submandibular+duct+relocation+for+drooling:+a+10-year+experience+with+194+patients.">Submandibular duct relocation for drooling: a 10-year experience with 194 patients.</a> Otolaryngol Head Neck. 101 (1), 87-92 (1989).</li><li>Squires, N., Wills, A., Rowson, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+management+of+drooling+in+adults+with+neurological+conditions.">The management of drooling in adults with neurological conditions.</a> Curr Opin Otolaryngol Head Neck Surg. 20 (3), 171-176 (2012).</li><li>Pickett, A., Perrow, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Formulation+composition+of+botulinum+toxins+in+clinical+use.">Formulation composition of botulinum toxins in clinical use.</a> J Drugs Dermatol. 9 (9), 1085-1091 (2010).</li><li>Barbero, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Long-term+follow-up+of+ultrasound-guided+botulinum+toxin-A+injections+for+sialorrhea+in+neurological+dysphagia.">Long-term follow-up of ultrasound-guided botulinum toxin-A injections for sialorrhea in neurological dysphagia.</a> J Neurol. 262 (12), 2662-2667 (2015).</li><li>Guidubaldi, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Botulinum+toxin+A+versus+B+in+sialorrhea:+a+prospective,+randomized,+double-blind,+crossover+pilot+study+in+patients+with+amyotrophic+lateral+sclerosis+or+Parkinson's+disease.">Botulinum toxin A versus B in sialorrhea: a prospective, randomized, double-blind, crossover pilot study in patients with amyotrophic lateral sclerosis or Parkinson's disease.</a> Mov Disord. 26, 313-319 (2011).</li><li>Standring, S., Gray, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Gray's anatomy: The anatomical basis of clinical practice. 41st ed. , 527 (2016).</li><li>Standring, S., Gray, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Gray's anatomy: The anatomical basis of clinical practice. 41st ed. , 504 (2016).</li><li>Standring, S., Gray, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Gray's anatomy: The anatomical basis of clinical practice. 41st ed. , 528 (2016).</li><li>Gomez-Caravaca, M. T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+use+of+botulinum+toxin+in+the+treatment+of+sialorrhea+in+parkinsonian+disorders.">The use of botulinum toxin in the treatment of sialorrhea in parkinsonian disorders.</a> Neurol Sci. 36 (2), 275-279 (2015).</li><li>Walter, U., Dressler, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ultrasound-guided+botulinum+toxininjections+in+neurology:+technique,+indications+and+future+perspectives.">Ultrasound-guided botulinum toxininjections in neurology: technique, indications and future perspectives.</a> Expert Rev Neurother. 14 (8), 923-936 (2014).</li><li>Thomas-Stonell, N., Greenberg, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Three+treatment+approaches+and+clinical+factors+in+the+reduction+of+drooling.">Three treatment approaches and clinical factors in the reduction of drooling.</a> Dysphagia. 3 (2), 73-78 (1988).</li><li>Sriskandan, N., Moody, A., Howlett, D. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ultrasound-guided+submandibular+gland+injection+of+botulinum+toxin+for+hypersalivation+in+cerebral+palsy.">Ultrasound-guided submandibular gland injection of botulinum toxin for hypersalivation in cerebral palsy.</a> Br J Oral Maxillofac Surg. 48 (1), 58-60 (2010).</li><li>Contarino, M. F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Botulinum+toxin+B+ultrasound-guided+injections+for+sialorrhea+in+amyotrophic+lateral+sclerosis+and+Parkinson's+disease.">Botulinum toxin B ultrasound-guided injections for sialorrhea in amyotrophic lateral sclerosis and Parkinson's disease.</a> Parkinsonism Relat Disord. 13 (5), 299-303 (2007).</li><li>Chinnapongse, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Safety+and+efficacy+of+botulinum+toxin+type+B+for+treatment+of+sialorrhea+in+Parkinson's+disease:+a+prospective+double-blind+trial.+Mov+Disord.">Safety and efficacy of botulinum toxin type B for treatment of sialorrhea in Parkinson's disease: a prospective double-blind trial. Mov Disord.</a> Mov Disord. 27 (2), 219-226 (2012).</li><li>Reid, S. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Secondary+effects+of+botulinum+toxin+injections+into+salivary+glands+for+the+management+of+pediatric+drooling.">Secondary effects of botulinum toxin injections into salivary glands for the management of pediatric drooling.</a> J Craniofac Surg. 24 (1), 28-33 (2013).</li><li>Chan, K. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Long-term+safety+and+efficacy+data+on+botulinum+toxin+type+A:+an+injection+for+sialorrhea.">Long-term safety and efficacy data on botulinum toxin type A: an injection for sialorrhea.</a> JAMA Otolaryngol Head Neck Surg. 139 (2), 134-138 (2013).</li><li>Petracca, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Botulinum+Toxin+A+and+B+in+sialorrhea:+Long-term+data+and+literature+overview.">Botulinum Toxin A and B in sialorrhea: Long-term data and literature overview.</a> Toxicon. 1 (107), 129-140 (2015).</li></ol>

The authors have nothing to disclose.

This protocol describes US-guided BoNT-A injection in the parotid and submandibular glands for the treatment of moderate to severe sialorrhea. Sialorrhea secondary to dysphagia is a frequent complication of the advanced stages of different neurological diseases, and when pharmacological therapy with anticholinergic agents demonstrates scarce efficacy or tolerability, salivary gland BoNT injection represents a useful therapeutic option2,7. However, salivary gland BoNT injection guided by anatomical landmarks ma...

流涎症は、脳卒中、脳性麻痺、多発性硬化症、および神経変性疾患1を含むいくつかの神経学的障害の共通の無効な合併症を表す唾液の過剰な流れです。中等度から重度の流涎症に罹患している患者は、生活の質が損なわれ、多くの場合、皮膚2の誤嚥性肺炎、口腔感染症、虫歯、および浸軟などの相関合併症、悪化しています。様々な治療オプションは、唾液の生産を減少させる目的で、手術からの薬物療法に至るまで、流涎症の治療のために利用可能です。 外科的選択肢は除神経、唾液腺の切除、および唾液の転置またはライゲーションが3,4ダクト含まれます。しかし、その有効性にもかかわらず、手術は定義により、このような唾液瘻と嚢胞形成、感染症の損失などの潜在的に重篤な有害事象、と侵襲的処置であります味、聴覚、構音障害、および唾液腺の生産3に対する不可逆的影響の損失。また、唾液がプロシージャ2,5-後2年以上腺の外科的アプローチが原因で再神経支配にのみ一時的効果を有し得ることが観察されています。重度の流涎症のためのより一般的かつ低侵襲性の治療は抗コリン作用特性を持つ全身薬の使用です。しかしながら、抗コリン作動薬の長期使用は、多くの場合、混乱、記憶障害、眠気、尿閉、および麻痺性イレウス2,5などの全身副作用を伴います。 ボツリヌス毒素毒素（BoNT）唾液注入は、流涎症のための新たな治療の選択肢です。 BoNTはで筋肉の収縮や腺の活動を阻止する、神経筋接合部のシナプス前神経終末からのアセチルコリン放出を停止することができます細菌のボツリヌス菌によって産生される（AからGへの7、）プロテアーゼ、あります交感神経性の副交感神経節後シナプス。 BoNTタイプA（のBoNT-A）およびタイプB（のBoNT-B）は、一般的ジストニアおよび痙縮6の治療管理のために使用されます。最近では、大唾液腺内のBoNT注射は、有効性の欠如または重大な副作用2,7,8の存在による他の医療療法に対する最適以下の応答を伴う重度の流涎症中等度において有用な治療選択肢であることが判明しました。 メジャーとマイナー：ヒト唾液腺には2つのグループに分類されます。大唾液腺は耳下腺のペア、顎下腺のペア、および舌下腺のペアを含みます。小唾液腺は口腔9のサブ粘膜内に広がる約1,000の小さな腺で構成されています。唾液の約0.5リットルは、一日あたりの分泌されます。大唾液腺の三対は、以下のようにおよそ分割、唾液産生の90％以上を担っている：20％Fまたは舌下腺9のための耳下腺、顎下腺のための65％、5％、。耳下腺は最大のものであり、下顎骨と胸鎖乳突筋との間で、外耳道の下に配置されています。それは咬筋10の表面には前方に突出します。重要な構造は、顔面神経、外頸動脈、および下顎後静脈、およびいくつかの他の重要な神経血管構造として、グランドを通過するには、腺の近くにあります。顎下腺は、顎下三角形の領域では、二腹筋の前部および後部の腹の間および顎舌骨筋11の後縁の周りに、下顎骨の枝の後ろと下に位置する混合腺です。 BoNT唾液腺注射は不快感および/または経口、TRなどの他の治療と相関全身性副作用を回避する可能性を有する局所治療でありますansdermal、および外科的選択肢。ここで、我々は強く、深刻なの発生を制限しながら、よだれの満足と長期的な減少を得るためのガイダンス（米国）超音波下耳下腺と顎下腺でのBoNT-Aの注射で流涎症を治療するために、簡単に信頼性と再現性のある方法を示し、有害事象。米国の指導の不在下で流涎症でのBoNT注入の有効性に関するデータは、文献12に報告されています。しかし、腺とその周囲組織のUS-導かれた識別は、針位置のリアルタイム可視化に伴って、増加した有効性と結果の再現性7,13につながる有害事象の低減と、より正確な注入を可能にします。

<table><tbody><tr><td>abobotulinumtoxinA (Dysport)</td><td>IpsenBiopharm, Wrexham, UK</td><td></td><td>Delivered drug</td></tr><tr><td>MyLab Twice</td><td>Esaote</td><td></td><td>Ultraonograph</td></tr><tr><td>LA523 5&amp;ndash;10 MHz</td><td>Esaote</td><td></td><td>Linear transducer</td></tr></tbody></table>

ultrasound-guided botulinum toxin-a injections: a method of treating sialorrhea

Neurological diseases can be complicated by sialorrhea, an excessive flow of saliva. Patients suffering from moderate to severe sialorrhea have an impaired quality of life, often worsened by correlated complications such as aspiration pneumonia, oral infections, dental caries, and maceration of the skin. Diverse therapeutic approaches have been proposed for the treatment of sialorrhea, including surgery and the use of anticholinergic agents, with limited results and the possible occurrence of serious adverse events. Recently, botulinum toxin (BoNT) injection within the major salivary glands has been proposed in patients refractory to anticholinergic therapy, with the aim of inhibiting local acetylcholine release and gland activity. 
In order to obtain a better outcome in terms of reduction of saliva production, efficacy, duration, and avoidance of major adverse events, we developed an ultrasound-guided BoNT-type A injection technique accurately described in the text. Here we present a method of treating sialorrhea with bilateral parotid and submandibular gland BoNT-type A injections under ultrasound guidance. Four quadrants of the parotid gland and two quadrants of the submandibular gland are visualized and injected using two accesses and one access, respectively. 
The ultrasound-guided procedure provides a simple, non-invasive, real-time visualization of the muscular and glandular tissues and their surrounding structures, optimizing treatment efficacy and safety.

US-導かれた注射は、リアルタイムおよび唾液腺中のBoNT投与のための正確な針の可視化を得るための有効な手法です。このアプローチは、長期の有効性および重篤な有害事象が存在しないと、信頼性の流涎症の治療を提供します。確かに、ここで提案されているUS-導かれたアプローチが提供する腺の針の浸透の可視化は重要かつ長期的な成果と大唾液腺内のBoNT-Aの広?...

Watch this Scientific Journal Video about Ultrasound-guided Botulinum Toxin-A Injections: A Method of Treating Sialorrhea at JoVE.com

Ultrasound-guided Botulinum Toxin-A Injections: A Method of Treating Sialorrhea

Botulinum toxin is injected into the salivary glands for the treatment of sialorrhea. The ultrasound-guided botulinum toxin injection in both the parotid and submandibular glands demonstrates a sustained efficacy and the absence of serious side effects.

ボツリヌス毒素Aの注射を超音波誘導：唾液分泌過多を治療する方法

Neurological diseases can be complicated by sialorrhea, an excessive flow of saliva. Patients suffering from moderate to severe sialorrhea have an ...

ultrasound-guided-botulinum-toxin-injections-method-treating

Universidad de Cartagena UDEC

Research

JoVE Journal

Medicine

22.6K ビュー.  University of Torino, San Luigi Gonzaga Hospital. Botulinum toxin is injected into the salivary glands for the treatment of sialorrhea. The ultrasound-guided botulinum toxin injection in both the parotid and submandibular glands demonstrates a sustained efficacy and the absence of serious side effects.

ビデオ: Ultrasound-guided Botulinum Toxin-A Injections: A Method of Treating Sialorrhea

Subcutaneous Neurotrophin 4 Infusion Using Osmotic Pumps or Direct Muscular Injection Enhances Aging Rat Laryngeal Muscles

Laryngeal dysfunction in the elderly is a major cause of disability, from voice disorders to dysphagia and loss of airway protective reflexes. Few, if any, therapies exist that target age-related laryngeal muscle dysfunction. Neurotrophins are involved in muscle innervation and differentiation of neuromuscular junctions (NMJs). It is thought that neurotrophins enhance neuromuscular transmission by increasing neurotransmitter release. The neuromuscular junctions (NMJs) become smaller and less abundant in aging rat laryngeal muscles, with evidence of functional denervation. We explored the effects of NTF4 for future clinical use as a therapeutic to improve function in aging human laryngeal muscles. Here, we provide the detailed protocol for systemic application and direct injection of NTF4 to investigate the ability of aging rat laryngeal muscle to remodel in response to NTF4 application. In this method, rats either received NTF4 either systemically via osmotic pump or by direct injection through the vocal folds. Laryngeal muscles were then dissected and used for histological examination of morphology and age-related denervation.

Here, we present a protocol to describe the use of neurotrophin 4 (NTF4) systemically and directly to remodel rat aging laryngeal muscles.

浸透圧ポンプまたは直接的筋肉注射を用いる皮下ニューロトロフィン4注入は、老齢ラット喉頭筋を増強する

Laryngeal dysfunction in the elderly is a major cause of disability, from voice disorders to dysphagia and loss of airway protective reflexes. Few, if ...

発生生物学

Retroductal Nanoparticle Injection to the Murine Submandibular Gland

Two common goals of salivary gland therapeutics are prevention and cure of tissue dysfunction following either autoimmune or radiation injury. By locally delivering bioactive compounds to the salivary glands, greater tissue concentrations can be safely achieved versus systemic administration. Furthermore, off target tissue effects from extra-glandular accumulation of material can be dramatically reduced. In this regard, retroductal injection is a widely used method for investigating both salivary gland biology and pathophysiology. Retroductal administration of growth factors, primary cells, adenoviral vectors, and small molecule drugs has been shown to support gland function in the setting of injury. We have previously shown the efficacy of a retroductally injected nanoparticle-siRNA strategy to maintain gland function following irradiation. Here, a highly effective and reproducible method to administer nanomaterials to the murine submandibular gland through Wharton's duct is detailed (Figure 1). We describe accessing the oral cavity and outline the steps necessary to cannulate Wharton's duct, with further observations serving as quality checks throughout the procedure.

Local drug delivery to the submandibular glands is of interest in understanding salivary gland biology and for the development of novel therapeutics. We present an updated and detailed retroductal injection protocol, designed to improve delivery accuracy and experimental reproducibility. The application presented herein is the delivery of polymeric nanoparticles.

マウス顎下腺への Retroductal ナノ粒子注入

Two common goals of salivary gland therapeutics are prevention and cure of tissue dysfunction following either autoimmune or radiation injury. By locally ...

生物工学

Retroductal Submandibular Gland Instillation and Localized Fractionated Irradiation in a Rat Model of Salivary Hypofunction

Normal tissues that lie within the portals of radiation are inadvertently damaged. Salivary glands are often injured during head and neck radiotherapy. Irreparable cell damage results in a chronic loss of salivary function that impairs basic oral activities, and increases the risk of oral infections and dental caries. Salivary hypofunction and its complications gravely impact a patient's comfort. Current symptomatic management of the condition is ineffective, and newer therapies to assuage the condition are needed. 
Salivary glands are exocrine glands, which expel their secretions into the mouth via excretory ducts. Cannulation of these ducts provides direct access to the glands. Retroductal delivery of a contrast agent to major salivary glands is a routine out-patient procedure for diagnostic imaging. Using a similar procedure, localized treatment of the glands is feasible. However, performing this technique in preclinical studies with small animals poses unique challenges. In this study we describe the technique of retroductal administration in rat submandibular glands, a procedure that was refined in Dr. Bruce Baum's laboratory (NIH)1, and lay out a procedure for local gland irradiation.

Salivary gland hypofunction, a major adverse effect of head and neck radiotherapy diminishes a patient's quality of life. The demonstration of efficacy of new therapies in animal models is a prerequisite before clinical transition. This protocol describes retroductal administration and local irradiation of rat submandibular glands.

唾液機能低下のラットモデルにおけるRetroductal顎下腺点滴とローカライズされた分割照射

Normal tissues that lie within the portals of radiation are inadvertently damaged. Salivary glands are often injured during head and neck radiotherapy. ...

医学

Subcutaneous Trigeminal Nerve Field Stimulation for Refractory Facial Pain

Chronic or neuropathic trigeminal facial pain can be challenging to treat. Neurosurgical procedures should be applied when conservative treatment fails. Neuromodulation techniques for chronic facial pain include deep brain stimulation and motor cortex stimulation, which are complex to perform. Subcutaneous nerve field stimulation is certified for chronic back pain and is the least invasive form of neuromodulation. We applied this technique to treat chronic and neuropathic trigeminal pain as an individual therapy concept. First, trial stimulation is performed. Subcutaneous leads are placed in the painful trigeminal dermatome under local anesthesia. The leads are connected to an external neurostimulator that applies constant stimulation. Patients undergo a 12 day outpatient trial to assess the effect of the stimulation. Electrodes are removed after the trial. If the patient reports pain reduction of at least 50% in intensity and/or attack frequency, a reduction in medication or increase in quality of life, permanent implantation is scheduled. New electrodes are implanted under general anesthesia and are subcutaneously tunneled to an infraclavicular internal pulse generator. Patients are able to turn stimulation on and off and to increase or decrease the stimulation amplitude as needed.
This technique represents a minimal invasive alternative to other more invasive means of neuromodulation for trigeminal pain such as motor cortex stimulation or deep brain stimulation.

Treating chronic or neuropathic facial pain can be challenging when medical or standard treatment fails. Subcutaneous nerve field stimulation is the least invasive form of neuromodulation and is used for chronic back pain. We applied this technology to treat chronic and neuropathic trigeminal facial pain.

難治性顔面痛のための皮下三叉神経刺激

Chronic or neuropathic trigeminal facial pain can be challenging to treat. Neurosurgical procedures should be applied when conservative treatment fails. ...

Retrograde Parotid Gland Infusion through Stensen's Duct in a Non-Human Primate for Vectored Gene Delivery

Salivary glands are an attractive tissue target for gene therapy with promising results already leading to human trials. They are inherently capable of secreting proteins into the bloodstream and are easily accessible, making them potentially superior tissue sites for replacement hormone production or vaccination by gene transfer. Suggested methods for gene delivery include transcutaneous injection and retrograde infusion through salivary ducts. We demonstrate how to perform Retrograde Salivary Gland Infusion (RSGI) in non-human primates. We describe the important anatomic landmarks including identification of the parotid papilla, an atraumatic method of cannulating and sealing Stensen&#39;s Duct utilizing basic dental tools, polyethylene tubing, and cyanoacrylate, and the appropriate rate of infusion. While this is the least traumatic method of delivery, the method is still limited by the volume able to be delivered (&#60;0.5 mL) and the potential for trauma to the duct and gland. We demonstrate using fluoroscopy that an infusate can be fully delivered into the gland, and further demonstrate by immunohistochemistry the transduction of a typical vector and expression of the delivered gene.

Salivary glands have been proposed as a tissue target site for gene therapy, especially in the area of vaccination by gene transfer. We demonstrate gene delivery in a non-human primate model utilizing retrograde parotid infusion.

ベクター化遺伝子導入のための非ヒト霊長類におけるステンセンダクトによる逆行性耳下腺注入

Salivary glands are an attractive tissue target for gene therapy with promising results already leading to human trials. They are inherently capable of ...

免疫・感染学

シェーグレン症候群の唾液腺超音波検査の技術

Ultrasonographic Evaluation of Salivary Glands for Sjogren's Syndrome: Diagnostic and Monitoring Insights

Sjogren's syndrome (SS) is a chronic autoimmune condition commonly affecting the exocrine glands, causing oral or ocular dryness and extraglandular manifestations including arthralgia, cytopenia, and lymphoma. The presence of autoantibodies against SSA/Ro, labial salivary gland biopsy, ocular staining, Schirmer's test, or salivary flow assessment are included in the current classification criteria of SS. However, the availability and invasiveness of these procedures limit their widespread use in clinical settings. Salivary gland ultrasonography (SGUS) is a non-invasive imaging modality for the evaluation of the salivary gland parenchyma and is increasingly utilized to aid diagnosis and monitoring in SS. 
This article presents the protocol of SGUS for image acquisition at the parotid and submandibular glands. The objective is to present a standardized, reproducible, and practical approach to diagnostic SGUS for SS in daily clinical settings. Major salivary glands are scanned in a stepwise approach, beginning at the angle of the mandible for the superficial lobe of the parotid gland, followed by the deep lobe below the ramus of the mandible. Submandibular areas are then scanned for the submandibular glands. The steps in obtaining salivary gland images at each anatomical site are explained in the accompanying video. The echogenicity and echotexture at the thyroid gland are taken as a reference. The homogeneity, the presence and distribution of hypoechoic areas within the glands, and the border of the salivary glands are examined. The sizes and features of intra-/peri-glandular lymph nodes are recorded. The most distinctive sonographic feature in SS is glandular heterogeneity with the presence of hypoechoic/hyperechoic areas within the glands. 
In summary, while SGUS cannot diagnose SS on its own, it can supplement the current classification criteria of SS and guide the clinical decision for salivary gland biopsy to support the diagnosis of SS in patients with sicca syndrome or suspicious systemic features, combined with autoantibody testing.

著者スポットライト:結合組織疾患研究における標準化された唾液腺超音波プロトコルへの注目

Salivary gland ultrasonography is a promising tool for the diagnosis and evaluation of disease activity and complications in Sjogren's syndrome (SS). The scanning technique for salivary gland ultrasound examination relevant to SS is described in the article.

シェーグレン症候群に対する唾液腺の超音波評価:診断とモニタリングの洞察

Sjogren's syndrome (SS) is a chronic autoimmune condition commonly affecting the exocrine glands, causing oral or ocular dryness and extraglandular ...

Innovative Approach to Minimize Serious Complications in Cosmetic Dermal Filling

Cosmetic dermal filling represents a significant advance in aesthetic medicine, providing non-invasive treatments with immediate and durable outcomes. Despite the generally safe nature of dermal fillers and avoidable complications with proper technique and planning, they are still risky, with potential complications varying from mild and transient to severe and enduring. This study introduces innovative strategies designed to decrease the risk of serious complications, such as vascular occlusion. These include the use of ultrasound guidance, the application of ice, auxiliary gestures, effective withdrawal, etc. Throughout our research, we observed no severe complications like embolism, skin necrosis, or ocular issues. However, minor complications such as erythema, edema, and bruising were noted. It is important to recognize that while most severe complications can be avoided with meticulous technique and planning, the inherent risk of unexpected outcomes persists in any medical procedure. Our findings suggest that with these innovative strategies, the safety of cosmetic dermal filling can be significantly enhanced, thereby minimizing the risk of severe adverse effects.

The protocol proposes an innovative approach to cosmetic dermal filling focusing on ultrasound, icing, pressing, auxiliary gestures, and effective withdrawal to reduce the risk of serious complications like vascular occlusion. Despite the general safety of dermal fillers, accidents can still occur because of the inherent risks.

Cosmetic dermal filling represents a significant advance in aesthetic medicine, providing non-invasive treatments with immediate and durable outcomes. ...

Nasolacrimal Lavage as a Treatment for Ocular Surface Toxic Soup Syndrome

Ocular surface toxic soup syndrome (OSTSS) is characterized by inadequate tear drainage through the nasolacrimal duct system, leading to the accumulation of inflammatory mediators in the tear film. This condition can result in toxic keratoconjunctivitis, with symptoms such as conjunctival hyperemia, itchiness, discomfort, and epiphora. Dilation and irrigation are common diagnostic procedures in both optometry and ophthalmology, used to assess nasolacrimal duct obstruction in cases of epiphora. This technique involves the injection of saline into the nasolacrimal duct system through the puncta, followed by the evaluation of reflux, which indicates obstruction. Although intended to be diagnostic, many patients report significant improvements in epiphora and ocular comfort after the procedure. In this paper, we present a case study in which a patient achieved complete resolution of epiphora and itchiness following therapeutic nasolacrimal lavage performed every 2 months. Subjective improvements in symptoms in 3 additional patients are also reported. We propose nasolacrimal lavage not only as a diagnostic tool but also as an effective therapeutic intervention for managing OSTSS.

OSTSS leads to pooled inflammatory mediators in the tear film, causing symptoms like epiphora and discomfort. Here, we present a case where therapeutic nasolacrimal lavage every 2 months resolved epiphora and itchiness, suggesting its efficacy as a therapeutic intervention for OSTSS. Additionally, we report subjective improvements in symptoms in 3 additional patients.

Ocular surface toxic soup syndrome (OSTSS) is characterized by inadequate tear drainage through the nasolacrimal duct system, leading to the accumulation ...

ボツリヌス毒素Aの注射を超音波誘導：唾液分泌過多を治療する方法

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浸透圧ポンプまたは直接的筋肉注射を用いる皮下ニューロトロフィン4注入は、老齢ラット喉頭筋を増強する

マウス顎下腺への Retroductal ナノ粒子注入

唾液機能低下のラットモデルにおけるRetroductal顎下腺点滴とローカライズされた分割照射

難治性顔面痛のための皮下三叉神経刺激

ベクター化遺伝子導入のための非ヒト霊長類におけるステンセンダクトによる逆行性耳下腺注入

シェーグレン症候群に対する唾液腺の超音波評価:診断とモニタリングの洞察

シェーグレン症候群に対する唾液腺の超音波評価:診断とモニタリングの洞察

シェーグレン症候群に対する唾液腺の超音波評価:診断とモニタリングの洞察

Innovative Approach to Minimize Serious Complications in Cosmetic Dermal Filling

Nasolacrimal Lavage as a Treatment for Ocular Surface Toxic Soup Syndrome