Botulinum neurotoxin type A in the interdisciplinary treatment of sialorrhea in adults and children-update and practice recommendations.

Sialorrhea is defined as a chronic excessive flow of saliva from the mouth, often with adverse consequences for health and quality of life of patients. In addition to currently used non-drug treatment and systemic drugs, intraglandular Botulinum Neurotoxin A (BoNT/A) injections have been examined in case studies, controlled trials and clinical practice. Two pivotal Phase III trials recently led to market approval in the USA and EU for IncobotulinumtoxinA [Xeomin®, IncoBoNT/A, Clostridium botulinum neurotoxin type A (150 kD), free from complexing proteins, Merz Pharmaceuticals GmbH] for treatment of chronic sialorrhea in adults and pediatric patients. This review provides a multidisciplinary approach to discuss the current state of sialorrhea therapy as well as benefits and current limitations of BoNT/A injections. A consensus regarding treatment recommendations made available to physicians in Germany in 2022 has now been updated here for presentation to an international audience. This review provides a framework including a flow chart for patient selection, recommendations for dosing and the injection process, as well as a discussion of therapeutic goals, long-term benefits and safety aspects. This review is aimed at supporting physicians in developing multidisciplinary and individualized treatment approaches to achieve optimal benefits for patients.

[Therapy of Sialorrhea with Botulinum Toxin - An Update]. / Therapie der Sialorrhoe mit Botulinumtoxin ­ ein Update.

The most important salivary glands are the paired parotid and submandibular glands. Adults produce 1 to 1.5 liters of saliva which are then regularly swallowed. When the act of swallowing is disturbed, salivation occurs. More rarely, the cause can be found in increased saliva production, for example, when caused through medication. Sialorrhea impairs the quality of life substantially and is frequently often socially stigmatizing. Therapy includes conservative measures such as functional dysphagia therapy, oral or transdermal application of anticholinergics, as well as, in selected cases, radiation and surgical measures. Over the last 20 years, local injection of botulinum toxin has been successfully applied in the treatment of this condition. With approval of incobotulinumtoxinA toxin for children and adults, this procedure will become the therapy of choice for chronic sialorrhea. The results of the phase III registration trials have demonstrated high efficacy and good safety of the injection treatment in both children and adults.

[Therapy of Hemifacial Spasm with Botulinum Toxin: an Update]. / Botulinumtoxin ­ Therapie des Spasmus hemifacialis: Ein Update.

Injections of botulinum toxin can be viewed by now as the therapy of choice in treating hemifacial spasm (HFS). Each of the three botulinum toxin-A preparations have been approved for this indication in Germany. HFS is a frequent disease characterized by involuntary contractions of the muscles of one half of the face innervated by the facial nerve. The symptoms can be either tonic or clonic, intermittant or permanent. Diagnosis is based purely on clinical observation. A magnetic resonance imagingof the skull is appropriate to demonstrate nerve-vessel contact as most frequent cause and to exclude other pathologies.

[Planning and design of European prospective randomized trial on the value of drain in parotidectomy]. / Vorstellung einer europaweiten prospektiven Studie zur Wertigkeit einer Drainage bei Parotidektomie.

INTRODUCTION: There are no valid clinical studies on the value of wound drains in parotid surgery. The aim of the current trial is to analyze the influence of the closed wound drain (redon) on the incidence of postoperative complications such as bleeding, wound healing problems, infection, as well as salivary cyst and fistula after superficial or partial parotidectomy. METHODS: A European-wide multicenter prospective randomized study was planned. The study protocol was prepared by the leading study center (ENT University Hospital Cologne) in cooperation with the ENT University Hospitals Jena and Göttingen. The calculation of the number of cases was carried out with G*Power. The study includes test persons with an indication for parotidectomy for a benign tumor without known coagulation disorder or ongoing anticoagulation. Preoperative randomization and data management is software-supported (REDCap 9.1.24, Vanderbilt University). RESULTS: The study has been approved by the leading ethics committee in 10/2019 and is open since 04/2019. Currently, nine (9) ENT hospitals are participating in the study, 6 of them in Germany and 3 in Austria. Enrollment of patients is ongoing in 7 centers. With a calculated follow-up-to-treat population of 800 test persons, the planned duration of the study is 4 years. CONCLUSIONS: The Redon-study is the first prospective randomized study worldwide to investigate the effect of a drain in parotidectomy. In order to achieve the recruitment goal within the planned time frame, the participation of further specialized study centers is needed. We also encourage all ENT physicians to make their patients aware of the Redon study, inform them about the possibility of participating in the study and refer them to one of the participating centers.

Therapy of Sialorrhea with Botulinum Neurotoxin.

Botulinum neurotoxin (BoNT) is considered the treatment of choice for various symptoms and diseases such as focal dystonia and focal spasticity. The effects of BoNT on the salivary glands have also been known for years, but their use was limited because of a lack of approval studies. Now the indication of sialorrhea is approved in some countries for incobotulinumtoxinA, such as the USA and Europe, and therapy could also become the treatment of choice. According to the pivotal study, a dose of 100 units of incobotulinumtoxinA, which is divided into the parotid and submandibular glands, is recommended. RimabotulinumtoxinB is approved in the USA only. To define the value of this therapy, we must consider anatomy, physiology, and available therapies. Therapy includes conservative measures such as functional dysphagia therapy, oral or transdermal application of anticholinergics, and, in selected cases, radiotherapy and surgical procedures. A combination of different approaches is optional. On the basis of the evidence and clinical experience, BoNT injections will be the first line of pharmacotherapy for chronic sialorrhea.

[Therapy of sialorrhea with botulinum toxin]. / Therapie der Sialorrhoe mit Botulinumtoxin.

The most important salivary glands are the paired parotid and submandibular glands. Adults produce 1 to 1.5 liters of saliva which are then regularly swallowed. When the act of swallowing is disturbed, salivation occurs. More rarely, the cause can be found in increased saliva production, for example, when caused through medication. Sialorrhea impairs the quality of life substantially and is frequently often socially stigmatizing. Therapy includes conservative measures such as functional dysphagia therapy, oral or transdermal application of anticholinergics, as well as, in selected cases, radiation and surgical measures. Over the last 20 years local injection of botulinum toxin has been successfully applied in the treatment of this condition. With approval of this therapy by the European agencies, this measure will become the therapy of choice for pronounced therapy-resistant sialorrhea.

[Hypersalivation - Update of the S2k guideline (AWMF) in short form]. / Hypersalivation ­ Aktualisierung der S2k-Leitlinie (AWMF) in gekürzter Darstellung.

Hypersalivation describes a relatively excessive salivary flow, which wets the patient himself and his surroundings. It may result because of insufficient oro-motor function, dysphagia, decreased central control and coordination. This update presents recent changes and innovation in the treatment of hypersalivation.Multidisciplinary diagnostic and treatment evaluation is recommended already at early stage and focus on dysphagia, saliva aspiration, and oro-motor deficiencies. Clinical screening tools and diagnostics such as fiberoptic endoscopic evaluation of swallowing generate important data on therapy selection and control. Many cases profit from swallowing therapy programmes in order to activate compensation mechanisms as long compliances is given. In children with hypotonic oral muscles, oral stimulation plates can induce a relevant symptom release because of the improved lip closure. The pharmacologic treatment improved for pediatric cases as glycopyrrolate fluid solution (Sialanar®) is now indicated for hypersalivation within the E. U. The injection of botulinum toxin into the salivary glands has shown safe and effective results with long lasting saliva reduction. Here, a phase III trial is completed for Incobotulinum toxin A and, in the U. S., is indicated for the treatment of adult patients with chronic hypersalivation. Surgical treatment should be reserved for isolated cases. External radiation is judged as a safe and effective therapy when using modern 3 D techniques to minimize tissue damage. Therapy effects and symptom severity has to be followed, especially in cases with underlying neurodegenerative disease.

[Therapy of Hemifacial Spasm with Botulinum Toxin]. / Therapie des Spasmus hemifacialis mit Botulinumtoxin.

Hemifacial spasm (HFS) is a frequent disorder characterized by involuntary contractions of those muscles innervated by the facialis nerve on one side of the face. The symptoms can appear as tonic or clonic, intermittent or permanent. Diagnosis is based purely on clinical observation. Differential diagnosis should rely on cranial MRI, which can demonstrate a pathological contact between the nerves and vessels and exclude alternative causation. Often, the symptoms are not marked so that therapy may not be necessary. The therapy of choice is an injection of botulinum toxin to reduce the underlying pathological activity. As an alternative, decompression operation according to Jannetta can be considered, although it is frequently rejected by patients.

Hypersalivation: update of the German S2k guideline (AWMF) in short form.

Hypersalivation describes a relatively excessive salivary flow, which wets the patient himself and his surroundings. It may result because of insufficient oro-motor function, dysphagia, decreased central control and coordination. This update presents recent changes and innovation in the treatment of hypersalivation. Multidisciplinary diagnostic and treatment evaluation is recommended already at early stage and focus on dysphagia, saliva aspiration, and oro-motor deficiencies. Clinical screening tools and diagnostics such as fiberoptic endoscopic evaluation of swallowing generate important data on therapy selection and control. Many cases profit from swallowing therapy programmes to activate compensation mechanisms as long compliances are given. In children with hypotonic oral muscles, oral stimulation plates can induce a relevant symptom release because of the improved lip closure. The pharmacologic treatment improved for pediatric cases as glycopyrrolate fluid solution (Sialanar®) is now indicated for hypersalivation within the EU. The injection of botulinum toxin into the salivary glands has shown safe and effective results with long-lasting saliva reduction. Here, a phase III trial is completed for incobotulinum toxin A and, in the US, is indicated for the treatment of adult patients with chronic hypersalivation. Surgical treatment should be reserved for isolated cases. External radiation is judged as a safe and effective therapy when using modern 3D techniques to minimize tissue damage. Therapy effects and symptom severity have to be followed, especially in cases with underlying neurodegenerative disease.

The incidence of occult metastasis and the status of elective neck dissection in salivary adenoid cystic carcinoma: a single center study.

OBJECTIVE: Adenoid cystic carcinoma (ACC) is characterized by a high rate of local recurrence and late distant metastasis. The status of an elective neck dissection (END) is controversial in the literature. STUDY DESIGN: In this study we retrospectively analyzed the surgical treatment and follow-up examinations of 59 patients with ACCs of a salivary gland treated in a single center between 1980 and 2016. RESULTS: The incidence of occult nodal metastases among all patients who underwent END was 20.6%. The overall survival and the disease-free survival of patients who underwent END versus patients without END had no significant differences. Even in the case of positive lymph nodes metastasis there was no significant benefit in survival or local recurrence control. CONCLUSION: The incidence of occult neck metastases in patients with ACC was 20.6%. There was no significant enhanced survival in the group of patients who underwent an END.

Clinical prognostic factors of salivary adenoid cystic carcinoma: A single-center analysis of 61 patients.

PURPOSE: Adenoid cystic carcinomas are rare malignant tumors of the salivary glands. They are characterized by a high rate of local recurrence, late distant metastasis and a poor disease-free survival. In this study, we analyzed a series of 61 patients who were all treated at the University of Göttingen over a period of 21.0 years. MATERIALS AND METHODS: In all 61 patients with salivary adenoid cystic carcinoma, clinical data, demographic data, risk factors, tumor location, tumor stage, status of surgical margin, surgical treatment, postoperative radiotherapy and follow-up interval were assessed. RESULTS: The overall survival (OS) and the disease-free survival (DFS) of patients who underwent surgery and those who underwent combined surgery with radiotherapy showed no significant differences. Neither did the T-stage (T1/T2 vs. T3/T4) show significant differences in OS and DFS. Only the status of the surgical margin was significantly associated with a longer OS and a longer DFS. CONCLUSION: The present results confirm that the radical surgical resection with clear tumor-free margins is the most important predictor for a longer survival. Adjuvant radiotherapy should be discussed from case to case, but should not be seen as an absolute prognostic factor for OS.

Deep neck infections: A single-center analysis of 63 cases

Background and Purpose: With the use of antibiotic therapy, the incidence of deep neck infections has decreased in recent decades. The aim of this investigation was to review the clinical course and the management of deep neck infections in our department, compare them to the experiences of the common literature and identify predisposing factors for lethal complications. Material and Methods: In this single-center analysis, 63 patients with deep neck infections were treated surgically. The following clinical data were analyzed and compared: age, gender, laboratory data, spatial manifestation, therapeutic modalities, comorbidities, length of hospitalization and complications. Results: There was a predominance of male patients (58.7%) and a mean age of 57.9 years. The most common symptoms at diagnosis were sore throat (96.8%) and neck swelling (92.0%). Cardio/pulmonary diseases and diabetes mellitus were the most common comorbidities. There was a significantly longer hospital stay for patients with diabetes mellitus. The most common manifestation was a parapharyngeal abscess in 24 patients (38.1%), followed by peri-/retrotonsillar infections in 19 patients (30.2%). In 29 patients, a multiple space infection was observed, with a significantly longer duration of hospitalization and a higher rate of complications. The main lifethreatening complication was the development of airway obstruction in 20 patients (31.7%), who all received a tracheostomy. The duration of hospitalization for patients with complications was significantly longer. Conclusions: Close attention must be paid to the management of patients with deep neck infections, especially patients with diabetes mellitus and cardio/pulmonary diseases or patients with multiple space infections (AU)

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[Treatment of laryngeal dystonia with botulinum toxin]. / Die Behandlung der laryngealen Dystonie mit Botulinumtoxin.

The treatment of laryngeal dystonias with botulinum toxin is successful. Every patient suffering from a laryngeal dystonia should be assured of high quality therapeutic intervention. Therefore it is important to establish general standards by experts in this field. In this connection, we want to focus here on different relevant aspects of laryngeal dystonias. This includes new aspects in etiology, anatomical landmarks for the injection, standards in diagnostics and therapy and finally open issues needing discussion.

[Therapy of Hemifacial Spasm with Botulinum Toxin]. / Therapie des Spasmus hemifacialis mit Botulinumtoxin.

Hemifacial spasm (HFS) is a frequent disorder characterized by involuntary contractions of those muscles innervated by the facialis nerve on one side of the face. The symptoms can appear as tonic or clonic, intermittent or permanent. Diagnosis is based purely on clinical observation. Differential diagnosis should rely on cranial MRI, which can demonstrate a pathological contact between the nerves and vessels and exclude alternative causation. Often, the symptoms are not marked so that therapy may not be necessary. The therapy of choice is an injection of botulinum toxin to reduce the underlying pathological activity. As an alternative, decompression operation according to Jannetta can be considered, although it is frequently rejected by patients.

Bacterial and histopathological findings in deep head and neck infections: a retrospective analysis.

OBJECTIVES: Deep neck infections are among the most dangerous acute diseases in the head and neck region. This analysis gives an overview of the bacterial and histopathologic findings of deep neck infections. STUDY DESIGN: From January 2002 to December 2012, 63 patients were diagnosed with and treated for deep neck infections at the University Medical Center Göttingen. Bacterial and histopathologic examinations were made, and the occurrence of bacterial pathogens and histopathologic findings were analyzed. RESULTS: The most commonly isolated aerobic gram-positive pathogen was Streptococcus viridans (26.7%); Staphylococcus epidermidis and Staphylococcus aureus were each found in 16.7% of infections. The most commonly isolated aerobic gram-negative pathogens were Escherichia coli, Klebsiella oxytoca, and Haemophilus influenzae. In 1.6% of patients, a malignant cancer was detected. CONCLUSION: For clear diagnosis and effective therapy, a bacteriologic investigation of deep neck infections is essential because of the heterogeneous spectrum of the detected bacteria. In contrast to Asia, where Klebsiella pneumoniae is the most common pathogen, in South Lower Saxony, Germany, we discovered a dominating spectrum of aerobic gram-positive cocci. Biopsy obtained from an abscess cavity for histologic examination should always be part of the diagnostic process in order to exclude a malignant process.

Frontalis suspension surgery to treat patients with blepharospasm and eyelid opening apraxia: long-term results.

Blepharospasm may be accompanied by eyelid opening apraxia (EOA) reducing the efficacy of botulinum toxin (BT) therapy. The frontalis suspension operation (FSO) is then the only effective treatment option available. We want to report the first long-term results with FSO. We studied 15 patients with blepharospasm and EAO unresponsive to BT therapy (9 females, 6 males, age 61.9 ± 11.5 years). FSO was performed by applying 2 polytetrafluoroethylene threads (PTFE, Gore-Tex®) per eye connecting the frontalis muscle to the upper eye lid. Tension of the two carrés was set to produce a palpebral fissure width of 2-3 mm. Therapy outcome was monitored by a quality-of-life questionnaire (QoL-Q) and a self-assessment calendar reviewing postoperative days 0-9 (T1), 10-89 (T2), 90-179 (T3), 180-365 (T4), and >365 days (T5). Altogether, 40 FSO were performed. Postoperatively, all patients reported improved eyelid opening, 4 (27%) complete remission of symptoms. At T1, this improvement was 74.6 ± 26.4% on the self-assessment scale, after 1 year 68.2 ± 27.5%. Throughout the observation period (T1-T5), the improvement was 71.9 ± 25.6%. All 19 items on the QoL-Q (except for presence of involuntary eye lid closure) showed postoperative improvement. Adverse effects included circumscript upper eyelid haematomas, suture extrusion, suture granuloma, lacrimation, and infections. In all patients, BT therapy had to be continued to treat orbicularis oculi contractions. Our first long-term results demonstrate that FSO is a benign procedure producing robust and stable therapeutic effects on EOA in blepharospasm.

Strategies for treatment of dystonia.

Treatment of dystonias is generally symptomatic. To produce sufficient therapy effects, therefore, frequently a multimodal and interdisciplinary therapeutic approach becomes necessary, combining botulinum toxin therapy, deep brain stimulation, oral antidystonic drugs, adjuvant drugs and rehabilitation therapy including physiotherapy, occupational therapy, re-training, speech therapy, psychotherapy and sociotherapy. This review presents the recommendations of the IAB-Interdisciplinary Working Group for Movement Disorders Special Task Force on Interdisciplinary Treatment of Dystonia. It reviews the different therapeutic modalities and outlines a strategy to adapt them to the dystonia localisation and severity of the individual patient. Hints to emerging and future therapies will be given.

Sialoendoscopy as a diagnostic and therapeutic option for obstructive diseases of the large salivary glands-a retrospective analysis.

OBJECTIVES: The diagnosis and therapy of obstructive inflammatory disorders of the salivary glands have changed in the past decades following the introduction of sialoendoscopy. The aims of the present study were to analyze the relevance of sialoendoscopy using our own data and to compare the results to those of other studies. PATIENTS AND METHODS: A retrospective analysis of 70 patients was performed, who were treated for obstructive disorders of the parotid and/or submandibular gland in whom sialoendoscopy was indicated. Two categories of interventions were considered: diagnostic interventional sialoendoscopy and endoscope-assisted interventions. Interventional sialoendoscopy procedures requiring extirpation of the gland were included in the analysis, as were abnormal intraductal processes that were detected during endoscopy. RESULTS: Treatment was successful in 58 of 67 (86.6 %) procedures (sialoendoscopy without surgical intervention n = 59; endoscope-assisted surgical intervention n = 8). Based on the underlying disease, the success rate was 88.6 % (n = 39) in patients with obstructive sialadenitis without sialolithiasis and 86.6 % (n = 19) in patients with sialolithiasis. It was not possible to draw definitive conclusions on the underlying disease from the observed pathological intraductal changes. CONCLUSIONS: Sialoendoscopy is an effective and safe diagnostic and therapeutic option with low complication rate. However, limiting factors such as the size or the position of potentially removable obstacles must be taken into consideration. CLINICAL RELEVANCE: The rate of gland extirpations can be reduced using sialoendoscopy.

Frontalis suspension surgery to treat patients with essential blepharospasm and apraxia of eyelid opening-technique and results.

INTRODUCTION: We describe the results of 15 patients suffering from essential blepharospasm with apraxia of eyelid opening who underwent frontalis suspension surgery. MATERIAL AND METHODS: Patients with apraxia of eyelid opening and unresponsive to botulinum toxin injections were studied. Bilateral frontalis suspension surgery was performed (sling operation) using polytetrafluoroethylene (Gore-Tex®) sutures. The patients reported the degree of improvement using a subjective rating scale to evaluate the benefit of the operation at two times after surgery (0-10 days and 180-360 days). RESULTS: The patients reported a high degree of subjective improvement. In the early postoperative period (0-10 days) the mean degree of subjective improvement was 74.6% (standard deviation (SD) 26.4%). At 180-360 days after surgery the mean improvement was 70.0% (SD 26.7%). Small hematomas of the upper lid occurred postoperatively in all patients. Other complications were suture extrusions (9.1%), suture granulomas (6.1%), lacrimation (5.0%) and local infections (7.5%). Postoperatively, all patients needed additional botulinum toxin injections for optimal outcome. CONCLUSION: Frontalis suspension surgery is a minimally invasive and effective treatment option for apraxia of eyelid opening in patients with essential blepharospasm unresponsive to botulinum toxin injections alone.