Parotid and submandibular botulinum toxin A injections for sialorrhoea in children with cerebral palsy

The aim of this study was to determine whether botulinum toxin A (BTX-A) injected into the parotid and submandibular salivary glands of children aged 6 to 16 years with cerebral palsy (CP) and relative sialorrhoea significantly decreases their drooling and improves their quality of life. Twenty children (10 males, 10 females; mean age 10y 1mo [SD 3y 8mo]; range 6y 1mo-16y 7mo) with CP, identified as having significant daily drooling (scoring at least 6 on drooling frequency/severity scales) were recruited. BTX-A (2U/kg; maximum 70U) was injected under sedation, using ultrasound guidance (1.4U/kg and 0.6U/kg divided between parotid and submandibular glands respectively). Nineteen children completed the study: 15 with spastic quadriplegia (Gross Motor Function Classification System [GMFCS] Level V); one with dystonia (GMFCS Level V); one with hemiplegia (GMFCS Level II); and two with a mixed pattern of CP (GMFCS Levels III and V). Drooling was assessed by five methods at baseline, and 4 and 12 weeks after injection. Qualitative assessment of drooling frequency and severity scores showed statistically significant reductions at 4 weeks (p<0.001) and 12 weeks (p=0.006). Qualitative assessment of quality of life scores (rated by parents and teachers separately) also significantly improved (p<0.001 and p=0.023 respectively). Quantitative assessments showed that the number of bibs/scarves changed per day was significantly reduced at 4 weeks (p<0.001). There was no side effect from the injections themselves; 89% of parents and children wished for further intrasalivary BTX-A injections in the future. We conclude that percutaneous intrasalivary BTX-A injections into the parotid and submandibular salivary glands can reduce drooling in children with CP and relative sialorrhoea, leading to an improvement in their quality of life.     

Ultrasound-guided versus 'blind' intraparotid injections of botulinum toxin-A for the treatment of sialorrhoea in patients with Parkinson's disease

OBJECTIVE: To investigate the efficacy and safety of intraparotid botulinum toxin-A (BTX-A) injections into parotid gland using ultrasound-guided versus nonguided techniques for the treatment of sialorrhoea in patients with Parkinson's disease (PD). METHODS: 15 patients with PD and sialorrhoea were included and divided into two groups. Group A patients (n=8) were injected with BTX-A using ultrasound guidance. Group B patients (n=7) were injected with BTX-A without ultrasound guidance. Saliva secretion was assessed quantitatively at baseline and at weeks 1, 4, and 12. Patients and/or caregivers also assessed the saliva secretion using visual analog scale (VAS). RESULTS: All patients except one reported subjective improvement in sialorrhoea at the first week. Group A patients showed significantly higher rate of saliva reduction at the first week, whereas in Group B the reduction was not statistically significant from baseline at the first week (P>0.05). Comparisons of quantitative saliva assessments at each follow-up visit also showed that ultrasound-guided injections were superior to blind injections for saliva reduction. VAS scores showed an improvement in the mean rate of saliva secretion in each group at first week (P<0.05). Two patients suffered from dry mouth in mild severity lasting 1 month. CONCLUSION: Intraparotid BTX-A injections using ultrasound guidance may be an effective, easy, and safe treatment for parkinsonian sialorrhoea.     

超声定位肌电图引导下A型肉毒毒素治疗重度流涎的临床观察

目的：评价A型肉毒毒素（BTX-A）治疗流涎的疗效。方法：选择流涎患者5例,其中帕金森病（PD）3例,脑梗死2例。采用教师流涎分级法（TDS）及流涎频率评分后于超声定位后肌电图引导下对患者腮腺和颌下腺进行BTX-A多点注射,于治疗前及治疗后2周、1个月和3个月时进行流涎测评。结果：TDS和流涎频率评分：BTX-A治疗前为（4.6±0.5）分和（3.0±0.0）分;BTX-A注射后2周降至（2.6±0.9）分和（1.6±0.5）分;1个月时为（2.8±1.1）分和（1.8±0.8）分,与治疗前比,差异有统计学意义（P〈0.05）;3个月时为（3.2±1.3）分和（2.0±1.0）分,与治疗前比,差异仍有统计学意义（P〈0.05）。5例患者均无明显并发症出现。结论：BTX-A局部注射治疗流涎是一种安全、有效的新方法。     

Successful management of drooling with botulinum toxin A in neurologically disabled children

OBJECTIVES: The present study investigates the effect of topical injections of botulinum toxin A into the cephalic salivary glands of children with chronic hypersalivation due to neurodegenerative diseases. METHODS: Five children with hypersalivation due to severe neurological diseases received, under ultrasound guidance, a total of 50-65 units of botulinum toxin A (Botox) into the parotid and submandibular glands on both sides. All injections were tolerated without local anaesthesia. Before and 1, 2, 4, 8 and 12 weeks after toxin injection, salivary flow rates and the concentrations of total protein, alpha-amylase, acid phosphatase, kallikrein, and immunoglobulin A were measured in the secretions; simultaneously, the patients were clinically examined with regard to severity of symptoms, and their salivary glands were subjected to ultrasound study. RESULTS: A distinct improvement of symptoms within the first 2 weeks following toxin administration were reported by the parents. Sialometry revealed considerably reduced flow rates but sialochemistry showed an increase of amylase activity. Ultrasound examination did not reveal any changes of the salivary parenchyma, and side-effects were absent. CONCLUSION: Treatment of drooling by topical injection of botulinum toxin A into the salivary glands is a reliable and also side-effect-free therapeutic option for children with neurological disorders. All children involved in our study experienced a distinct improvement of their quality of life.     

Quantitative reduction of saliva production with botulinum toxin type B injection into the salivary glands

Drooling is common in patients with neurological disorders. Recently, botulinum toxin type B has been shown to be effective in the treatment of drooling. The authors present a unique case of a 57-year-old man with a history of a brainstem stroke and severe drooling. The patient's parotid and submandibular glands were injected under ultra-sound guidance with botulinum toxin type B. Saliva was collected and quantified before and after the injections by 2 different collection methods: suctioning and dental rolls. Total saliva production decreased by 23.8% after injection of the parotid glands and by 85.8% after submandibular injection compared to the preinjection level. The 2 methods demonstrated similar results. In addition, the patient experienced less drooling and increased participation in therapies without any side effects. This case demonstrates that saliva secretion and drooling can effectively be treated by injections of botulinum toxin type B into the salivary glands.     

Radiotherapy reduces sialorrhea in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder. Sialorrhea is a frequent problem in ALS patients with bulbar symptoms, because of progressive weakness of oral, lingual and pharyngeal muscles. This prospective study aimed to investigate the putative effect of palliative single-dose radiotherapy on problematic sialorrhea in patients with ALS. Twenty patients with ALS and problematic drooling were included; 14 were given radiotherapy with a single fraction of 7.5 Grey (Gy). Five patients were treated with botulinum toxin A (BTX-A) injections (20 U) into the parotid glands; two of these were later given radiotherapy. Symptom assessment, clinical examination and measurements of salivary flow (ml/min) were performed before and after treatment (1–2 weeks, 3 months). Salivary secretion was significantly reduced after radiation treatment, with a mean reduction of 60% (1 week) and 51% (2 weeks). Three months post-treatment, 21% reduction of the salivary secretion was observed compared with salivation before treatment. Mean salivary flow was not reduced after BTX-A treatment in five patients. No serious side-effects were observed with either of the two treatment modalities. Single-dose radiotherapy (7.5 Gy) significantly reduces sialorrhea and is an effective and safe palliative treatment in patients with ALS.     

Botulinum toxin injections for children with excessive drooling

The objective of this study was to evaluate the feasibility of ultrasonography-guided injections of botulinum toxin A into the parotid glands of children with severe drooling (sialorrhea). Excessive drooling is common in children with chronic neurologic disorders. Preliminary observations in adults suggest that injections of botulinum toxin A into the parotid glands can decrease drooling, but the optimal dose, sites of injection, and concomitant use of imaging during injections and its use for children have not been established. Ultrasonography was used to guide the injection of botulinum toxin (10-25 IU) into both parotid glands of nine children with excessive drooling. Subjective and objective measures of the severity of drooling were collected before and after botulinum toxin A injections. A booster injection was provided if the initial response was inadequate. Injections were well tolerated, and no adverse reactions were observed. Ultrasonography revealed that the parotid gland showed a variable depth, extent, and vascularization. Eight of nine patients needed a booster injection after 1 month. Objective measures of drooling severity were improved in seven of nine patients. However, subjective improvement was reported in only three of nine patients, and this improvement was functionally significant in only one patient. Although intraparotid injection of botulinum toxin A is safe and causes a reduction in saliva production in children, the doses used in this study did not result in functionally significant improvement. Higher doses of botulinum toxin A in the parotid glands or concomitant injections into the submandibular glands can increase the efficacy of these injections. Variability in size, depth, and vascular supply of the parotid gland suggests the importance of ultrasonography guidance for optimizing injections. These results underscore the need for further studies to establish the efficacy of this treatment in children.     

Botulinum toxin B reduces sialorrhea in parkinsonism.

We report on our open-label experience with botulinum toxin B for the treatment of severe sialorrhea associated with parkinsonism. Nine adult patients with parkinsonism and medically intractable sialorrhea were treated with botulinum toxin B (1,000 units into each parotid gland using superficial landmarks). After treatment, patients experienced a 61% mean subjective improvement and a 42% mean reduction of quantitative saliva production. There were no adverse effects seen in any subjects. Mean peak benefit from injections lasted 14 weeks. We conclude that denervation of salivary glands with botulinum toxin B produces excellent reduction of excessive salivation associated with parkinsonism.     

Botulinum toxin A for drooling in Parkinson's disease: a pilot study to compare submandibular to parotid gland injections

Drooling is a common and incapacitating problem in Parkinson's disease (PD). Treatment with botulinum neurotoxin (BoNT) into the parotid glands seems beneficial. Injection of the submandibular glands may also be effective since these produce 70% of the daily unstimulated saliva. We randomly allocated patients to BoNT injections into the submandibular glands or the parotid glands. Within-group improvements were significant for the submandibular group, but not for the parotid group. Between-group differences showed a trend towards superiority for the submandibular group. Injecting the submandibular glands instead of the parotid glands seems a promising approach, and larger studies are justified.     

The effect of chorda tympani section on ipsilateral and contralateral salivary secretion and taste in man.

Bilateral chorda tympani section is an accepted treatment for troublesome sialorrhoea. Nevertheless the effects of this operation have been poorly studied. Twenty patients were studied with unilateral chorda tympani section and a healthy contralateral ear. The effects on ipsilateral and contralateral stimulated submandibular and parotid flow and taste recognition and detection thresholds were measured. Stimulated submandibular flow accounted for only 27% of the total salivary flow. Chorda tympani section had no effect on submandibular flow in seven patients and only reduced submandibular flow by approximately 54% in the remaining 13 patients. No significant effect was observed on ipsilateral parotid flow rate. Electrogustometric taste detection thresholds were more than twice the accepted upper limit of normal on the lesioned side and taste recognition thresholds were also markedly abnormal. Chorda tympani section alone is a poor method of reducing stimulated salivary flow.     

肌电图引导下A型肉毒毒素治疗痉挛性斜颈146例临床研究

目的:探讨肌电图引导下A型肉毒毒素局部肌肉注射治疗原发性痉挛性斜颈的疗效。方法:对146例痉挛性斜颈患者在肌电图引导下进行A型肉毒毒素局部肌肉注射,观察其治疗效果以及不良反应。结果:146例痉挛性斜颈患者,治疗后Tsui量表评分明显下降;重复治疗者复发症状减轻,治疗剂量下降,疗效仍良好。所有患者均未见严重不良反应。结论:肌电图引导下A型肉毒毒素局部肌肉注射是一种治疗痉挛性斜颈有效和安全的手段。     

Problems with botulinum toxin treatment in mitochondrial cytopathy: case report and review of the literature

Botulinum toxin type A (BTXA) is widely used in neurological therapeutics for a variety of indications such as dystonia, spasticity, hyperhidrosis, and hypersalivation. It is relatively contraindicated in disorders of neuromuscular transmission, in individuals with known hypersensitivity or bleeding disorders, and during pregnancy. Two patients are presented with initially undetermined multisystem neurological disorders and excessive sialorrhoea, later diagnosed as mitochondrial cytopathy, who had side effects after treatment with ultrasound guided BTXA injections. Published reports on the use of BTXA injections in hypersalivation of various causes are reviewed, along with the proposed mechanisms of hypersensitivity to BTXA in patients with mitochondrial cytopathies. Clinicians should be cautious when using BTXA injections in such patients because of the significant risk of side effects.     

Acute amitriptyline effects on parasympathetic-evoked rat saliva

The present study was undertaken to investigate the acute effects of amitriptyline on salivary secretion evoked by electrical stimulation of the parasympathetic innervations of rat salivary glands. Single intravenous injections of amitriptyline (0.1-1 mg/kg) caused a dose-related decrease in flow and Na concentration of saliva from both parotid and submandibular glands. However, the only effect on K concentration was a slight increase when the salivary flow was almost completely inhibited. Amitriptyline increased the Ca concentration of nerve-evoked submandibular saliva, but had no effect on the Ca concentration of similarly evoked parotid saliva. However, amitriptyline (0.5 and 1 mg/kg) increased the protein concentration of both kinds of saliva. Amylase activity of parotid saliva was also moderately increased by amitriptyline. These effects were similar to those observed with atropine, a known cholinergic receptor antagonist. These results suggest that amitriptyline, like atropine, reduces parasympathetic-evoked salivary secretion by blocking cholinergic receptors.     

External radiation of the parotid glands significantly reduces drooling in patients with motor neurone disease with bulbar paresis.

The parotid glands and part of the submandibular glands were irradiated in 18 amyotrophic lateral sclerosis patients with very advanced disease and severe drooling problems. In a prospective study, a single dosage of 7.0-7.5 Gy was administered bilateral to the larger part of the parotid glands and the posterior parts of the submandibular glands. Salivary secretion rate was assayed before and after radiotherapy. Sixteen out of eighteen patients reported satisfactory to good reduction in drooling lasting up to 4-6 months, 1/18 developed xerostomia and needed saliva substitutes, and 1/18 reported no effect. Caregivers reported positive effect in all patients. The procedure was well tolerated with few side effects. Low dosage external radiotherapy of the salivary glands is effective in reducing drooling satisfactorily in ALS patients, especially in well-hydrated patients.     

Drooling: are botulinum toxin injections into the major salivary glands a good treatment option?

There are several treatment options available for drooling; botulinum toxin injections into the major salivary glands are one. There is no consensus as to how many and which glands should be injected. A research project on this topic was terminated because of adverse effects. Individual results and the adverse effects are described and discussed in this article. Six individuals with cerebral palsy were randomly allocated to 2 treatment groups, with five individuals receiving ultrasound-guided injections to parotid and submandibular glands and one receiving injections to the submandibular glands only. Reduction of observed drooling was registered in 3, while 4 patients reported subjective improvement (Visual Analog Scale). Two participants reported adverse effects, including dysphagia, dysarthria, and increased salivary viscosity. Injections with botulinum toxin can be a useful treatment option but there is a risk of adverse effects. Multidisciplinary evaluation and informed discussions with patients/caregivers are important factors in the decision-making process.     

Randomized trial of botulinum toxin injections into the salivary glands to reduce drooling in children with neurological disorders

The primary aim of this randomized, controlled trial was to assess the effectiveness of botulinum toxin A (BoNT-A) injections into the submandibular and parotid glands on drooling in children with cerebral palsy (CP) and other neurological disorders. Secondary aims were to ascertain the duration of any such effect and the timing of maximal response. Of the 48 participants (27 males, 21 females; mean age 11y 4mo [SD 3y 3mo], range 6-18y), 31 had a diagnosis of CP and 15 had a primary intellectual disability; 27 children were non-ambulant. Twenty-four children randomized to the treatment group received 25 units of BoNT-A into each parotid and submandibular gland. Those randomized to the control group received no treatment. The degree and impact of drooling was assessed by carers using the Drooling Impact Scale questionnaire at baseline and at monthly intervals up to 6 months postinjection/baseline, and again at 1 year. Maximal response was at 1 month at which time there was a highly significant difference in the mean scores between the groups. This difference remained statistically significant at 6 months. Four children failed to respond to the injections, four had mediocre results, and 16 had good results. While the use of BoNT-A can help to manage drooling in many children with neurological disorders, further research is needed to fully understand the range of responses.     

Does botulinum toxin decrease frequency and severity of sialorrhea in Parkinson's disease?

This study analysed if botulinum toxin type A (BTX-A) decreases drooling in 21 Parkinson's disease patients. BTX-A injections were given in the parotid glands. The severity of drooling decreased in 18 (86%) patients, while frequency was reduced in 8 (38%). In 11(52%) patients, the frequency of drooling remained constant, which may reflect more difficulties in swallowing, compared to the group that presented such improvement. Future trials assessing the level of swallowing dysfunction may be important to establish a prognosis for patients who keep the frequency of drooling in spite of decreased severity after BTX injection.     

Beta-adrenergic receptors and cAMP levels of rat parotid and submandibular glands during chronic isoproterenol treatment

The number of cell surface beta-adrenergic receptors and the level of cyclic AMP of the parotid and the submandibular gland were examined in rats treated for up to 10 days with twice daily injections of the beta-adrenergic agonist, isoproterenol. Receptor densities of 125 +/- 8.7 fmol/mg membrane protein for the parotid and 60.1 +/- 5.6 fmol/mg for the submandibular glands were found with [3H]dihydroalprenolol (beta-adrenergic receptor antagonist) binding of glands from control rats. No change from levels of controls was found in the number of beta-receptors of the submandibular gland with chronic isoproterenol stimulation; the parotid glands, on the other hand, showed a 22% decrease in dihydroalprenolol binding from the 4th until the 8th day of treatment. By day 10 of isoproterenol treatment the parotid gland demonstrated a shift from a population consisting of primarily beta-adrenergic receptors to one consisting of equal numbers of beta 1- and beta 2-adrenoceptors. The basal level of cAMP present in cell lysates remained unchanged in the isoproterenol-treated submandibular gland while the parotid gland showed a 30-40% decrease. Control and isoproterenol-treated animals demonstrated the same time course of cAMP accumulation after a single challenge with isoproterenol.     

Reduced MIBG accumulation of the parotid and submandibular glands in idiopathic Parkinson's disease

IntroductionAlpha-synuclein pathology (ASP) is a characteristic histopathological finding in idiopathic Parkinson's disease (PD). The ASP involves not only the brain but also extracranial structures. In the present study we utilized MIBG scintigraphy to measure the sympathetic innervation of the major salivary glands. We were interested in whether MIBG uptake in the major salivary glands represents a potential biomarker for ASP in PD.MethodsWe investigated 77 PD patients (age 61 ± 10 years, mean ± SD), while 15 non-PD patients (age 58 ± 15 years) with arterial hypertension, who underwent MIBG scintigraphy to exclude pheochromocytoma, served as age-matched controls. The MIBG uptake of the parotid glands and the submandibular glands was quantified by means of a region of interest technique. The sublingual glands were too small for an exact measurement. We applied Generalized Estimating Equations (GEE) to identify and remove factors which may bias the statistical correlation analysis.ResultsThe PD patients showed a significantly lower MIBG uptake in the parotid and submandibular glands than the controls (p < 0.0001). MIBG uptake in the PD patients did not correlate with clinical severity (Hoehn and Yahr stage, motor part of the UPDRS) or disease duration.ConclusionMIBG uptake in the parotid and submandibular glands might be a candidate biomarker for PD. The missing correlation between MIBG uptake and clinical PD parameters suggests that ASP of the extracranial sympathetic superior cervical ganglion, which innervates the major salivary glands, develops independently from the cerebral dopaminergic nigrostriatal ASP.     

Double-blind, placebo-controlled study to evaluate the efficacy and safety of botulinum toxin type A in the treatment of drooling in parkinsonism.

Drooling is a frequent symptom in Parkinson's disease (PD), occurring in almost 75% of all patients. Although it is now well known that drooling in PD is the result of swallowing difficulties rather than excessive saliva production, few treatments have been developed to reduce it. Clinical studies suggest that botulinum toxin A (BTX) injections into salivary glands are effective in decreasing drooling in PD patients. In this double-blind, placebo-controlled study, 20 patients with parkinsonism (idiopathic PD or multiple system atrophy), were randomly assigned to receive 450 U of BTX (Dysport; Ipsen, Berkshire, UK) or 2 ml of placebo, injected into the parotids and submandibular glands under ultrasonographic guidance. Treatment efficacy and safety were assessed at baseline, 1 week and 3 months after BTX injections using clinical scales (Drooling Severity and Drooling Frequency scales) and side effects surveillance. After treatment, the average secretion of saliva in the BTX group was significantly lower than in the placebo group, as appraised by clinical measurements. No side effects were observed in either group. BTX injection into parotids and submandibular glands, under ultrasonographic guidance, is an effective and safe treatment for drooling in parkinsonism.