Therapie der Sialorrhoe mit Botulinumtoxin

Zusammenfassung

Die größten Speicheldrüsen sind die paarigen Gl. parotis und Gl. submandibularis. Der erwachsene Mensch produziert 1–1,5 l Speichel am Tag, die er regelmäßig abschluckt. Die häufigste Ursache eines vermehrten Speichelflusses mit einer Ansammlung von Speichel im Mund und Ausfluss (Sialorrhoe) ist eine Störung der Schluckfunktion. Seltener kann die Ursache auch eine vermehrte Speichelsekretion, z. B. medikamentös bedingt, sein. Eine Sialorrhoe beeinträchtigt die Lebensqualität erheblich und ist oft auch sozial stigmatisierend. Die Therapie umfasst konservative Maßnahmen wir die funktionelle Dysphagietherapie, orale oder transdermale Applikation von Anticholinergika sowie, in ausgewählten Fällen, invasive Therapien wie Bestrahlungen und Operationen. Seit 20 Jahren wird auch die lokale Injektion von Botulinumtoxin in die Speicheldrüsen erfolgreich therapeutisch eingesetzt. Durch die Zulassung dieser Therapie durch die europäische Behörde darf diese Maßnahme als Therapie der Wahl bei ausgeprägter, therapieresistenter Sialorrhoe angesehen werden.

Abstract

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.

Schlüsselwörter

Sialorrhoe - Dysphagie - Anticholinergika - Botulinumtoxin

Key words

sialorrhea - dysphagia - anticholinergics - botulinum toxin

• Literatur

• 1 Kochar A, Larian B, Azizzadeh B. Facial nerve and parotid gland anatomy. Consortium on drooling. Otolaryngol Clin North Am 2016; 49: 273-284
• 2 Pedersen AML, Sörensen CE, Proctor GB. et al. Salivary secretion in health and disease. J Oral Rehabil 2018; 45: 730-746
• 3 Proctor GB, Carpenter GH. Salivary secretion: Mechanism and neural regulation. Monogr Oral Sci 2014; 24: 14-29
• 4 Holmberg KV, Hoffman MP. Anatomy, biogenesis and regeneration of salivary glands. Monogr Oral Sci 2014; 24: 1-13
• 5 Matsuo R. Role of saliva in the maintenance of tast sensitivity. Crit Rev Oral Biol Med 2000; 11: 216-229
• 6 Tabak LA, Levine MJ, Mandel ID. et al. Role of salivary mucins in the protection of the oral cavity. JCOral Pathol 1982; 11: 1-17
• 7 Blasco PA, Allaire JH. Drooling in the developmentally disabled: Management practices and recommendations. Consortium on Drooling. Dev Med Child Neurol 1992; 34: 849-862
• 8 van Hulst K, van Den Engel-Hoek L, Geurts ACH. et al. Development of the Drooling Infants and Preschoolers Scale (DRIPS) and reference charts for monitoring saliva control in children aged 0–4 years. Infant Behav Dev 2018; 50: 247-256
• 9 Verma R, Anand KS. Botulinum toxin: A novel therapy for clozapine-induced sialorrhoea. Psychopharmacology (Berl) 2018; 235: 369-371
• 10 Camp-Bruno JA, Winsberg BG, Green-Parsons AR. et al. Efficacy of benztropine therapy for drooling. Dev Med Child Neurol 1989; 31: 309-319
• 11 Crysdale WS, White A. Submandibular duct relocation for drooling: A 10-year experience with 194 patients. Otolaryngol Head Neck Surg 1989; 101: 87-92
• 12 Thomas-Stonell N, Greenberg J. Three treatment approaches and clinical factors in the reduction of drooling. Dysphagia 1988; 3: 73-78
• 13 Blasco PA. Management of drooling: 10 years after the consortium on drooling, 1990. Dev Med Child Neurol 2002; 44: 778-781
• 14 Ellies M, Rohrbach-Volland S, Arglebe C. et al. Successful management of drooling with botulinum toxin A in neurologically disabled children. Neuropediatrics 2002; 33: 327-330
• 15 Crysdale WS, McCann C, Roske L. et al. Saliva control issues in the neurologically challenged. A 30 year experience in team management. Int J Pediatr Otorhinolaryngol 2006; 70: 519-527
• 16 Steffen A, Ortfeld S, Schönweiler R. Drooling bei neuropädiatrischen Patienten – ein Update. Klin Padiatr 2011; 223: 5-9
• 17 Bartolome G. Aspirationsschnelltests und Klinische Schluckuntersuchung. In: Bartolome G. Schröter-Morasch H. eds. Schluckstörungen – Diagnostik und Rehabilitation. 5. Aufl.. München: Elsevier; 2014
• 18 Langmore SE, Schatz K, Olsen N. Fiberoptic endoscopic examination of swallowing safety: A new procedure. Dysphagia 1988; 2: 216-219
• 19 Schröter-Morasch H, Graf S. Dysphagiediagnostik durch den HNO-Arzt. HNO 2014; 62: 324-334
• 20 Murray J, Langmore SE, Ginsberg S. et al. The significance of accumulated oropharyngeal secretions and swallowing frequency in predicting aspiration. Dysphagia 1996; 11: 99-103
• 21 Reynolds J, Carroll S, Sturdivant C. Fiberoptic endoscopic evaluation of swallowing: A multidisciplinary alternative for assessment of infants with dysphagia in the neonatal intensive care unit. Adv Neonatal Care 2016; 16: 37-43
• 22 Diesener P. Schluckstörungen bei Kindern: Bildgebende Diagnostik mittels transnasaler Videoendoskopie. Prakt Pädiatrie 1999; 5: 36-42
• 23 Bader C, Niemann G. Dysphagie bei Kindern mit Infantiler Zerebralparese – Fiberoptisch – Endoskopische Befunde. Laryngorhinootologie 2010; 89: 90-94
• 24 Rohrbach S, Gross M. Die transnasale fiberoptisch-endoskopische Schluckuntersuchung (FEES) bei Kindern - Standardisiertes diagnostisches Vorgehen. Monatsschr Kinderh 2014; 162: 329-333
• 25 Holzapfel K. Radiologische Diagnostik von Schluckstörungen. In: Bartolome G. Schröter-Morasch H. Hrsg. Schluckstörungen – Diagnostik und Rehabilitation. 5. Aufl.. München: Elsevier; 2014
• 26 Olthoff A, Carstens PO, Zhang S. et al. Evaluation of dysphagia by novel real-time MRI. Neurology 2016; 87: 2132-2138
• 27 Olthoff A, Joseph AA, Weidenmüller M. et al. Real-time MRI of swallowing: Intraoral pressure reduction supports larynx elevation. NMR Biomed 2016; 29: 1618-1623
• 28 Bartolome G. Grundlagen der funktionellen Dysphagietherapie (FDT). In: Bartolome G. Schröter-Morasch H. Hrsg. Schluckstörungen – Diagnostik und Rehabilitation. München-Jena: Urban & Fischer; 2010: 245-370
• 29 Hinchey JA, Shephard T, Furie K. et al. Formal dysphagia screening protocols prevent pneumonia. Stroke 2005; 36: 1972-1976
• 30 Carnaby G, Hankey GJ, Pizzi J. Behavioural intervention for dysphagia in acute stroke: A randomised controlled trial. Lancet Neurol 2006; 5: 31-37
• 31 Prosiegel M, Bartolome G, Biniek R. et al. Rehabilitation neurogener Dysphagien. In: HC D. Hrsg. Leitlinien für Diagnostik und Therapie in der Neurologie. Stuttgart: Thieme; 2008: 908-919
• 32 Mikami DLY, Furia CLB, Welker AF. Addition of kinesio taping of the orbicularis oris muscles to speech therapy rapidly improves drooling in children with neurological disorders. Dev Neurorehabil 2017; 21: 1-6
• 33 Hussein I, Kershaw AE, Tahmassebi JF. et al. The management of drooling in children and patients with mental and physical disabilities: A literature review. Int J Paediatr Dent 1998; 8: 3-11
• 34 Limbrock GJ, Hoyer H, Scheying H. Drooling, chewing and swallowing dysfunctions in children with cerebral palsy: Treatment according to Castillo-Morales. ASDC J Dent Child 1990; 57: 445-451
• 35 De Simone GG, Eisenchlas JH, Junin M. et al. Atropine drops for drooling: A randomized controlled trial. Palliat Med 2006; 20: 665-671
• 36 Hyson HC, Johnson AM, Jog MS. Sublingual atropine for sialorrhea secondary to parkinsonism: A pilot study. Mov Disord 2002; 17: 1318-1320
• 37 Matos Santana TE, Capurso NA, Ranganathan M. et al. Sublingual atropine in the treatment of clozapine-induced sialorrhea. Schizophr Res 2017; 182: 144-145
• 38 Fischbacher L, Schröter-Morasch H. Medikamentöse Speichelreduktion bei Neurogener Dysphagie. In: Gross M. Kruse E. , Hrsg. Aktuelle phoniatrische-pädaudiologische Aspekte 2003 / 2004. Band 11. Niebüll: Medicombooks.de im Verlag videel; 2003
• 39 Blasco PA, Stansbury JC. Glycopyrrolate treatment of chronic drooling. Arch Pediatr Adolesc Med 1996; 150: 932-935
• 40 Bachrach SJ, Walter RS, Trzcinski K. Use of glycopyrrolate and other anticholinergic medications for sialorrhea in children with cerebral palsy. Clin Pediatr (Phila) 1998; 37: 485-490
• 41 Mier RJ, Bachrach SJ, Lakin RC. et al. Treatment of sialorrhea with glycopyrrolate: A double-blind, dose-ranging study. Arch Pediatr Adolesc Med 2000; 154: 1214-1218
• 42 Man WH, Colen-de Koning JC, Schulte PF. et al. The Effect of glycopyrrolate on nocturnal sialorrhea in patients using clozapine: A randomized, crossover, double-blind, placebo-controlled trial. J Clin Psychopharmacol 2017; 37: 155-161
• 43 Blissit KT, Tillery E, Latham C. et al. Glycopyrrolate for treatment of clozapine-induced sialorrhea in adults. Am J Health Syst Pharm 2014; 71: 1282-1287
• 44 Lee ZI, Yu KJ, Lee DH. et al. The effect of nebulized glycopyrrolate on posterior drooling in patients with brain injury: Two cases of different brain lesions. Am J Phys Med Rehabil 2017; 96: e155-e158
• 45 Praharaj SK, Munoli RN, Sharma PS. Low-dose glycopyrrolate for clozapine-associated sialorrhea. J Clin Psychopharmacol 2014; 34: 392
• 46 Banfi P, Ticozzi N, Lax A. et al. A review of options for treating sialorrhea in amyotrophic lateral sclerosis. Respir Care 2015; 60: 446-454
• 47 Qurashi I, Chu S, Husain N. et al. Glycopyrrolate in comparison to hyoscine hydrobromide and placebo in the treatment of hypersalivation induced by clozapine (GOTHIC1): Study protocol for a randomised controlled feasibility study. Trials 2016; 17: 553
• 48 Parr JR, Weldon E, Pennington L. et al. The drooling reduction intervention trial (DRI): A single blind trial comparing the efficacy of glycopyrronium and hyoscine on drooling in children with neurodisability. Trials 2014; 15: 60
• 49 Zeller RS, Davidson J, Lee HM. et al. Safety and efficacy of glycopyrrolate oral solution for management of pathologic drooling in pediatric patients with cerebral palsy and other neurologic conditions. Ther Clin Risk Manag 2012; 8: 25-32
• 50 Zeller RS, Lee HM, Cavanaugh PF. et al. Randomized Phase III evaluation of the efficacy and safety of a novel glycopyrrolate oral solution for the management of chronic severe drooling in children with cerebral palsy or other neurologic conditions. Ther Clin Risk Manag 2012; 8: 15-23
• 51 Uppal HS, De R, D’Souza AR. et al. Bilateral submandibular duct relocation for drooling: An evaluation of results for the Birmingham Children’s Hospital. Eur Arch Otorhinolaryngo 2003; 260: 48-51
• 52 Katona G, Csákányi Z, Lorincz A. et al. Bilateral submandibular duct relocation by high-frequency radiosurgery. Eur Arch Otorhinolaryngol 2008; 265: 1103-1108
• 53 Mankarious LA, Bottrill ID, Huchzermeyer PM. et al. Long-term follow-up of submandibular duct rerouting for the treatment of sialorrhea in the pediatric population. Otolaryngol Head Neck Surg 1999; 120: 303-307
• 54 Martin TJ, Conley SF. Long-term efficacy of intra-oral surgery for sialorrhea. Otolaryngol Head Neck Surg 2007; 137: 54-58
• 55 Reed J, Mans CK, Brietzke SE. Surgical management of drooling: A meta-analysis. Arch Otolaryngol Head Neck Surg 2009; 135: 924-931
• 56 Becmeur F, Schneider A, Flaum V. et al. Which surgery for drooling in patients with cerebral palsy? J Pediatr Surg 2013; 48: 2171-2174
• 57 Formeister EJ, Dahl JP, Rose AS. Surgical management of chronic sialorrhea in pediatric patients: 10- year experience from one tertiary care institution. Int J Pediatr Otorhinolaryngol 2014; 78: 1387-1392
• 58 Noonan K, Prunty S, Ha JF. et al. Surgical management of chronic salivary aspiration. Int J Pediatr Otorhinolaryngol 2014; 78: 2079-2082
• 59 Kok SE, van der Burg JJ, van Hulst K. et al. The impact of submandibular duct relocation on drooling and the well-being of children with neurodevelopmental disabilities. Int J Pediatr Otorhinolaryngol 2016; 88: 173-178
• 60 Feussner H, Schröter-Morasch H. Chirurgische Interventionen bei Schluckstörungen. In: Bartolome G. Schröter-Morasch H. Hrsg. Schluckstörungen – Diagnostik und Rehabilitation. 5. Aufl.. München: Elsevier; 2014
• 61 Lawson G, Remacle M. Endoscopic cricopharyngeal myotomy: Indications and technique. Curr Opin Otolaryngol Head Neck Surg 2006; 14: 437-441
• 62 Seegenschmiedt MH, Makoski HB, Trott KR. et al. Sialorrhea / Hypersalivation. In: Seegenschmiedt MH. Makoski HB. Trott KR. et al., eds. Radiotherapy for non-malignant disorders. Berlin: Springer; : 573-579 2008
• 63 Andersen PM, Grönberg H, Franzen L. et al. External radiation of the parotid glands significantly reduces drooling in patients with motor neurone disease with bulbar paresis. J Neurol Sci 2001; 191: 111-114
• 64 Borg M, Hirst F. The role of radiation therapy in the management of sialorrhea. Int J Radiat Oncol Biol Phys 1998; 41: 1113-1119
• 65 Neppelberg E, Haugen DF, Thorsen L. et al. Radiotherapy reduces sialorrhea in amyotrophic lateral sclerosis. Eur J Neurol 2007; 14: 1373-1377
• 66 Postma AG, Heesters M, van Laar T. Radiotherapy to the salivary glands as treatment of sialorrhea in patients with parkinsonism. Mov Disord 2007; 22: 2430-2435
• 67 Assouline A, Levy A, Abdelnour-Mallet M. et al. Radiation therapy for hypersalivation: A prospective study in 50 amyotrophic lateral sclerosis patients. Int J Radiat Oncol Biol Phys 2014; 88: 589-595
• 68 Weikamp JG, Schinagl DA, Verstappen CC. et al. Botuninum toxin-A injections vs. radiotherapy for drooling in ALS. Acta Neurol Scand 2016; 134: 224-231
• 69 Hawkey NM, Zaorsky NG, Galloway TJ. The role of radiation therapy in the management of sialorrhea: A systematic review. Laryngoscope 2016; 126: 80-85
• 70 Steffen A, Wollenberg B, Schönweiler R. et al. Drooling nach Strahlentherapie – Botulinumtoxin als erfolgreiches Therapieverfahren. HNO 2011; 59: 115-117
• 71 Xu H, Shan XF, Cong X. et al. Pre- and post-synaptic effects of botulinum toxin A on submandibular glands. J Dent Res 2015; 94: 1454-1462
• 72 Bhatia KP, Münchau A, Brown P. Botulinum toxin is a useful treatment in excessive drooling in saliva. J Neurol Neurosurg Psychiatry 1999; 67: 697
• 73 Bushara KO. Sialorrhea in amyotrophic lateral sclerosis: A hypothesis of a new treatment–Botulinum toxin A injections of the parotid glands. Med Hypotheses 1997; 48: 337-339
• 74 Jost WH. Treatment of drooling in Parkinson’s disease with botulinum toxin. Mov Disord 1999; 14: 1057
• 75 Jost WH, Friedman A, Michel O. et al. SIAXI: Placebo-controlled, randomized, double-blind study of incobotulinumtoxinA for sialorrhea. Neurology 2019; 92: e1982-e1991
• 76 Chaléat-Valayer E, Porte M, Buchet-Poyau K. et al. Management of drooling in children with cerebral palsy: A French survey. Eur J Paediatr Neurol 2016; 20: 524-531
• 77 Dashtipour K, Bhidayasiri R, Chen JJ. et al. RimabotulinumtoxinB in sialorrhea: Systematic review of clinical trials. J Clin Mov Disord 2017; 4: 9
• 78 Dogu O, Apaydin D, Sevim S. et al. Ultrasound-guided versus ‘blind’ intraparotid injections of botulinum toxin-A for the treatment of sialorrhoea in patients with Parkinson’s disease. Clin Neurol Neurosurg 2004; 106: 93-96
• 79 Egevad G, Petkova VY, Vilholm OJ. Sialorrhea in patients with Parkinson’s disease: Safety and administration of botulinum neurotoxin. J Parkinsons Dis 2014; 4: 321-326
• 80 Mazlan M, Rajasegaran S, Engkasan JP. et al. A double-blind randomized controlled trial investigating the most efficacious dose of botulinum toxin-A for sialorrhea. Treatment in asian adults with neurological diseases. Toxins (Basel) 2015; 7: 3758-3770
• 81 Ko SH, Shin YB, Min JH. et al. Botulinum toxin in the treatment of drooling in tetraplegic patients with brain injury. Ann Rehabil Med 2013; 37: 796-803
• 82 Mancini F, Zangaglia R, Cristina S. et al. Double-blind, placebo-controlled study to evaluate the efficacy and safety of botulinum toxin type A in the treatment of drooling in parkinsonism. Mov Disord 2003; 18: 685-688
• 83 Martínez-Poles J, Nedkova-Hristova V, Escribano-Paredes JB. et al. Incobotulinumtoxin A for sialorrhea in neurological disorders: A real-life experience. Toxins (Basel) 2018; 10: pii: E217
• 84 Narayanaswami P, Geisbush T, Tarulli A. et al. Drooling in Parkinson’s disease: A randomized controlled trial of incobotulinum toxin A and meta-analysis of Botulinum toxins. Parkinsonism Relat Disord 2016; 30: 73-77
• 85 Restivo DA, Panebianco M, Casabona A. et al. Botulinum toxin A for sialorrhoea associated with neurological disorders: Evaluation of the relationship between effect of treatment and the number of glands treated. Toxins (Basel) 2018; 10: pii: E55
• 86 Stokholm MG, Bisgård C, Vilholm OJ. Safety and administration of treatment with botulinum neurotoxin for sialorrhoea in ALS patients: Review of the literature and a proposal for tailored treatment. Amyotroph Lateral Scler Frontotemporal Degener 2013; 14: 516-520
• 87 Giess R, Naumann M, Werner E. et al. Injections of botulinum toxin A into the salivary glands improve sialorrhoea in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 2000; 69: 121-123
• 88 George KS, Kiani H, Witherow H. Effectiveness of botulinum toxin B in the treatment of drooling. Br J Oral Maxillofac Surg 2013; 51: 783-785
• 89 Ondo WG, Hunter C, Moore W. A double-blind placebo-controlled trial of botulinum toxin B for sialorrhea in Parkinson’s disease. Neurology 2004; 62: 37-40
• 90 Winterholler MG, Erbguth FJ, Wolf S. et al. Botulinum toxin for the treatment of sialorrhoea in ALS: Serious side effects of a transductal approach. J Neurol Neurosurg Psychiatry 2001; 70: 417-418
• 91 Steffen A, Jost W, Bäumer T. et al. Hypersalivation: Update of the German S2k guideline (AWMF) in short form. J Neural Transm (Vienna) 2019 . doi:10.1007/s00702-019-02000-4
• 92 Scott J. Age, sex and contralateral differences in the volumes of human submandibular salivary glands. Arch Oral Biol 1975; 20: 885-887
• 93 Ono K, Morimoto Y, Inoue H. et al. Relationship of the unstimulated whole saliva flow rate and salivary gland size estimated by magnetic resonance image in healthy young humans. Arch Oral Biol 2006; 51: 345-349
• 94 So JI, Song DH, Park JH. et al. Accuracy of ultrasound-guided and non-ultrasound-guided botulinum toxin injection into cadaver salivary glands. Ann Rehab Med 2017; 41: 51-57
• 95 McGeachan AJ, McDermott CJ. Management of oral secretions in neurological disease. Pract Neurol 2017; 17: 96-103
• 96 Jost WH. The option of sonographic guidance in botulinum toxin injection for drooling in Parkinson’s disease. J Neural Transm 2016; 123: 51-55
• 97 Chinnapongse R, Gullo K, Nemeth P. et al. Safety and efficacy of botulinum toxin type B for treatment of sialorrhea in Parkinson’s disease: A prospective double-blind trial. Mov Disord 2012; 27: 219-226
• 98 Guidubaldi A, Fasano A, Ialongo T. et al. 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. Mov Disord 2011; 26: 313-319
• 99 Jackson CE, Gronseth G, Rosenfeld J. et al. Randomized double-blind study of botulinum toxin type B for sialorrhea in ALS patients. Muscle Nerve 2009; 39: 137-143
• 100 Lagalla G, Millevolte M, Capecci M. et al. Botulinum toxin type a for drooling in Parkinson’s disease: A double-blind, randomized, placebo-controlled study. Mov Disord 2006; 5: 704-707
• 101 Lagalla G, Millevolte M, Capecci M. et al. Long-lasting benefits of botulinum toxin type B in Parkinson’s disease-related drooling. J Neurol 2009; 256: 563-567
• 102 Lipp A, Trottenberg T, Schink T. et al. A randomized trial of botulinum toxin A for treatment of drooling. Neurology 2003; 61: 1279-1281
• 103 Reid SM, Johnstone BR, Westbury C. et al. Randomized trial of botulinum toxin injections into the salivary glands to reduce drooling in children with neurological disorders. Dev Med Child Neurol 2008; 50: 123-128
• 104 Steinlechner S, Klein C, Moser A. et al. Botulinum toxin B as an effective and safe treatment for neuroleptic-induced sialorrhea. Psychopharmacology (Berl) 2010; 207: 593-597