Name: ultrasound-guided botulinum toxin-a injections: a method of treating sialorrhea
Uploaded: 2016-11-09T12:30:00
Description: Watch this Scientific Journal Video about Ultrasound-guided Botulinum Toxin-A Injections: A Method of Treating Sialorrhea at JoVE.com

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

Here, we technically describe the method used for the treatment of sialorrhea in patients with neurological dysphagia. We will not focus on efficacy results, which have been published previously7. In this paper, in the results section, we present data from 5 consecutive patients with long-term follow-up (3 treatment sessions) treated from 2014 to 2016. These patients are considered representative of the entire population, which consists of the botulinum toxin service of San Luigi Gonzaga Hospital. The protocol was approved and fol...

<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>

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...

Sialorrhea is an excessive flow of saliva representing a common and disabling complication of several neurological disorders, including stroke, cerebral palsy, multiple sclerosis, and neurodegenerative diseases1. 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 skin2. Various therapeutic options are available for the treatment of sialorrhea, ranging from surgery to pharmacological therapy, with the aim of reducing saliva production.
Surgical options include denervation, excision of the salivary glands, and transposition or ligation of the salivary ducts3,4. However, despite its efficacy, surgery is by definition an invasive procedure with potentially serious adverse events, such as salivary fistula and cyst formation, infections, loss of taste, loss of hearing, dysarthria, and irreversible effects on salivary gland production3. In addition, it has been observed that surgical approaches may have only temporary efficacy due to reinnervation of the salivary glands two or more years after the procedure2,5. A more common and less invasive treatment for severe sialorrhea is the use of systemic drugs with anticholinergic properties. However, the chronic use of anticholinergic agents is often associated with systemic side effects such as confusion, memory problems, drowsiness, urinary retention, and paralytic ileus2,5.
Botulinum toxin (BoNT) salivary injection is an emerging treatment option for sialorrhea. BoNT are proteases (seven, from A to G), produced by the bacterium Clostridium botulinum, that are able to halt acetylcholine release from the presynaptic nerve terminals of the neuromuscular junction, blocking muscle contraction and gland activity at the orthosympathetic and parasympathetic postganglionic synapses. BoNT type A (BoNT-A) and type B (BoNT-B) are commonly used for therapeutic management of dystonia and spasticity6. Recently, BoNT injection within the major salivary glands proved to be a useful therapeutic option in moderate to severe sialorrhea with suboptimal response to other medical therapies due to a lack of efficacy or the presence of significant side effects2,7,8.
Human salivary glands are classified into two groups: major and minor. Major salivary glands include a pair of parotid glands, a pair of submandibular glands, and a pair of sublingual glands; the minor salivary glands consist of about 1,000 small glands spread within the sub-mucosa of the oral cavity9. Approximately 0.5 liters of saliva are secreted per day. The three pairs of major salivary glands are responsible for more than 90% of the saliva production, approximately divided as follows: 20% for the parotid glands, 65% for the submandibular glands and 5%, for the sublingual glands9. The parotid gland is the largest one and is located below the external acoustic meatus, between the mandible and the sternocleidomastoid muscle; it projects forward on the surface of the masseter muscle10. Important structures pass through the gland, such as the facial nerve, external carotid artery, and retromandibular vein, and several other important neurovascular structures are close to the gland. The submandibular gland is a seromucous gland situated behind and below the ramus of the mandible, in the region of the submandibular triangle, between the anterior and posterior bellies of the digastric muscle and around the posterior border of the mylohyoid muscle11.
BoNT salivary gland injection is a local treatment with the potential to avoid discomfort and/or systemic side effects correlated with the other therapies, such as oral, transdermal, and surgical options. Here, we show a reliable and easily reproducible method to treat sialorrhea with BoNT-A injections in the parotid and submandibular glands under ultrasound (US) guidance in order to obtain a satisfying and long-lasting reduction of drooling while strongly limiting the occurrence of serious adverse events. Data on BoNT-A injection efficacy in sialorrhea in the absence of US guidance are reported in the literature12; however, the US-guided identification of glands and their surrounding tissues, along with real-time visualization of the needle position, allows for a reduction in adverse events and a more accurate injection, leading to increased efficacy and outcome reproducibility7,13.

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			<td>abobotulinumtoxinA (Dysport)&#160;</td>
			<td>&#160;IpsenBiopharm, Wrexham, UK</td>
			<td></td>
			<td>Delivered drug</td>
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			<td>MyLab &#160;Twice&#160;</td>
			<td>Esaote</td>
			<td></td>
			<td>Ultraonograph</td>
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			<td>LA523 5&#8211;10 MHz&#160;</td>
			<td>Esaote</td>
			<td></td>
			<td>Linear transducer</td>
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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.

The US-guided injection is an effective technique to obtain real-time and precise needle visualization for BoNT administration in the salivary glands. This approach provides a reliable sialorrhea treatment, with prolonged efficacy and the absence of serious adverse events. Indeed, the visualization of the glands and of the needle penetration provided by the US-guided approach proposed here allows a widespread administration of BoNT-A within the major salivary glands with significant and l...

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.

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

The overall goal of this procedure is to provide a simple and reliable method to treat sialorrhea by botulinum toxin salivary gland injection, in order to obtain a long lasting efficacy, and a limited rate of minor side effects. This method can help neurologists and doctors involved in the treatment of sialorrhea to improve their salivary gland botulinum toxin injection technique. The main advantage of this method is that through ultrasound guidance, and simple rules of injection, it is possible to obtain reproducible and long lasting outcome in the treatment of sialorrhea, and limiting potential side effects.Generally, individuals new to this method will struggle because the use of ultrasound guidance may appear challenging and time consuming. On the contrary, the easy ultrasound identification of the salivary gland and the possibility to inject the small submandibular gland led to the higher treatment success rate. Widening the therapeutic effect duration.Begin by placing the patient on the ultrasound table in the supine position, with their neck extended. Use antiseptic to disinfect the skin in the area of the parotid and the submandibular glands. Next, turn on the ultrasound systems, and press the start/end button to begin the exam.Press the probe button to select the high frequency probe. Then, press the patient button to enter the patient's first name, and last name. Press the depth button, and specify the depth of view to five centimeters.Following that, press the focus button to select the maximum detail of two centimeters. Next, place the transducer under the mandible between the anterior and posterior bellies of the digastric muscle, in order to visualize the submandibular gland, which should appear as a hypoechoic area with homogenous echotexture, compared to the surrounding tissues. Finally, place the transducer below the external acoustic meatus, to visualize the parotid gland, which should also appear as a hypoechoic area with homogenous echotexture, compared to the surround tissues.For the injection, acquire a 22 gauge needle, and use a lateral short access approach at the widest gland diameter to access the submandibular gland. Inject 25 IU of botulinum toxin, or boNT-A, into the upper submandibular quadrant. After the injection, slightly retract the needle and change the direction of the needle tip towards the lower submandibular quadrant.Inject another 25 IU of boNT-A for a total of 50 IU in each submandibular gland. Dab any bleeding with steril gauze for one to two minutes. Next, for the parotid gland injection, identify two access sites midway between the external auditory canal, and the mandible angle, where one is in the cranial part of the gland, and the other in the caudal part of the gland.Then, use the upper access site in the cranial part of the gland to inject 18 to 19 IU of boNT-A into the medial cranial quadrant. After the injection, slightly retract the needle without leaving the site of the cranial part of the gland, and change the direction of the needle tip towards the lateral cranial quadrant. Inject another 18 to 19 IU of boNT-A.Next, use the lower access site in the caudal part of the gland to inject 18 to 19 IU of boNT-A into the medial caudal quadrant. Then, slightly retract the needle without leaving the site of the caudal part of the gland, and change the direction of the needle tip towards the lateral caudal quadrant. Inject a final 18 to 19 IU of boNT-A for a total of 75 IU boNT-A in the four parotid areas.Finally, dab any residual bleeding with steril gauze. Keep the patient for one hour to monitor any potential adverse events. Notice, the drooling frequency and severity scale, or DFSS scores, showed a significant reduction in both variables from pre-treatment to one month after treatment.The visual analog scale used, evaluated the patient's objective sufferance related to the sialorrhea, and showed higher scores, meaning an increase in overall comfort from pre-treatment to one month after treatment. Additionally, the need for daily saliva aspirations also lowered from pre-treatment to the one month follow up. Once mastered, the technique can be completed in about 15 minutes, if it is performed properly.After watching this video, you should have a good understanding on how to place the transducer in order to visualize the submandibular and the parotid glands, and identify how to move the needle tip in order to treat the whole glandular tissue with the standard botulinum toxin dose. Don't forget, that working with needles can be dangerous. Precaution, such as the use of gloves and safety measures for removal and disposal of needle are always required, to reduce the risk of accidental injury and infectious diseases.

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