The Role of Radiation Therapy and Botulinum Toxin Injections in the Management of Sialorrhea in Patients With Amyotrophic Lateral Sclerosis: A Systematic Review.

OBJECTIVES: Half of patients with amyotrophic lateral sclerosis experience sialorrhea due to facial weakness. Although anticholinergic medications are first-line therapy, they often lead to unacceptable side effects. Radiation therapy and botulinum toxin may be considered when medical management fails. In this systematic review, we investigated the effectiveness of these interventions. METHODS: Eligible studies were retrieved from PubMed and Scopus databases up to March 2017 along with hand-searching of references from primary articles. RESULTS: Fourteen studies (N = 138) examined the benefits of botulinum toxin. Studies varied in salivary glands treated, dosages used, and the use of botulinum toxin subtype A or B. A majority of studies showed benefit after treatment. Although most studies reported only mild adverse effects, 2 case studies revealed severe complications including recurrent TMJ dislocations and rapid deterioration in bulbar function. Ten studies (N = 171) examined the benefits of radiation. Most studies reported improvement with only mild adverse events reported. CONCLUSIONS: Both radiation and botulinum toxin are effective treatments for sialorrhea in patients with amyotrophic lateral sclerosis and should be considered when medical management fails. Radiation may offer longer duration of symptom improvement with fewer complications.

Tracheostomy and salivary gland radiotherapy for severe sialorrhoea in motor neurone disease.

The management of excessive secretions in patients with motor neurone disease can be challenging. In this paper, we highlight the main issues from the perspectives of a patient, specialist nurse and neurologist and the importance of a multidisciplinary approach.

Botulinum toxin-A injections vs radiotherapy for drooling in ALS.

OBJECTIVES: Botulinum neurotoxin (BoNT) injections in the salivary glands and radiotherapy (RT) on these glands are commonly used to alleviate severe drooling in patients with amyotrophic lateral sclerosis (ALS). This study compares BoNT type A with RT based on patient-rated evaluations. MATERIALS & METHODS: A prospective randomized controlled pilot study to compare RT (n = 10; on the parotid and the posterior part of the submandibular glands) with BoNT-A treatment (n = 10; in the parotid glands only, because of the risk of increasing oropharyngeal weakness) in patients with ALS. The primary outcome was the drooling status (burden of drooling), and our secondary interests were the degree of salivation, global change of drooling after treatment, and level of satisfaction with the treatment and negative experiences. RESULTS: There were no statistically significant between-treatment differences for the drooling status after treatment. Only at twelve weeks more saliva reduction was achieved by RT (P = 0.02). Patients treated with RT also described more transient negative experiences (like pain in mandible) directly after treatment. Subgroup analysis showed that patients with very severe dysphagia (no oral intake) were less satisfied and experienced a lower global change of drooling after treatment. CONCLUSIONS: This pilot study showed no significant difference in the burden of drooling between the treatments. However, with RT more saliva reduction was achieved, including negative experiences directly after treatment, but without the risk of decreasing oropharyngeal function. In addition, patients with very severe dysphagia do not seem to benefit from either treatment.

The role of radiation therapy in the management of sialorrhea: A systematic review.

PURPOSE: Up to 80% of patients with Parkinson disease and 30% of patients with amyotrophic lateral sclerosis (ALS) suffer from sialorrhea. Patients who fail medical and surgical therapy should be considered for external beam radiation therapy (EBRT). In this study, we conduct a systematic review to determine the dose and techniques used that result in greatest efficacy and lowest toxicity for the administration of EBRT in patients with Parkinson disease or ALS-associated sialorrhea. METHODS AND MATERIALS: This review included 216 patients from four prospective and six retrospective studies published from 1998 to 2014, with ALS or Parkinson disease who were treated with electron or photon EBRT for sialorrhea. RESULTS: A total of 216 patients were treated with EBRT from 10 studies. The indication for EBRT was failure of alternative medical treatment in all ALS patients. For patients with Parkinson disease, EBRT was the primary mode of treatment in 68% of cases. Overall, 176 (81%) of 216 patients treated with EBRT for sialorrhea reported symptomatic improvement from baseline. The most common target was the inferior two-thirds of the bilateral parotid glands and the entire bilateral submandibular glands. The total number of patients who experienced short-term toxicity was 86 of 216 patients (40%). The total number of patients who experienced long-term toxicity was 24 of 207 (12%). CONCLUSIONS: EBRT is an effective treatment for sialorrhea in patients suffering from ALS or Parkinson disease. Treatment to the bilateral submandibular glands and caudal parotid glands is the most common field arrangement.

Managing excessive saliva with salivary gland irradiation in patients with amyotrophic lateral sclerosis.

OBJECTIVE: A significant fraction of patients with amyotrophic lateral sclerosis (ALS) are unable to swallow saliva, which may result in the spillage of saliva outside of the oral cavity. Although anticholinergic agents and botulin toxin injections are considered the first line of treatment, they have not been effective for all patients. We performed a literature search on therapeutic salivary gland irradiation in patients with ALS. METHODS: We searched the PubMed for English language publications up to December 2014 on therapeutic salivary gland irradiation in patients with ALS. The search was performed using the following key words: amyotrophic lateral sclerosis, excessive salivation, sialorrhea, and radiation therapy. RESULTS: The majority of ALS patients with excessive salivation respond well to salivary gland irradiation. The whole bilateral submandibular, and whole or partial bilateral parotid glands have been the target tissue for radiation therapy in most of the published studies. Various radiation therapy regimens have been utilized. The response to radiation therapy lasts for several months. CONCLUSIONS: The majority of ALS patients with excessive salivation respond well to salivary gland irradiation. Neurologists should consider this treatment option for select patients with ALS and excessive salivation.

Radiation therapy for hypersalivation: a prospective study in 50 amyotrophic lateral sclerosis patients.

PURPOSE: This study aimed to evaluate the efficiency and the tolerance of radiation therapy (RT) on salivary glands in a large series of amyotrophic lateral sclerosis (ALS) patients with hypersalivation. METHODS AND MATERIALS: Fifty ALS patients that had medically failure pretreatment were included in this prospective study. RT was delivered through a conventional linear accelerator with 6-MV photons and 2 opposed beams fields including both submandibular glands and two-thirds of both parotid glands. Total RT dose was 10 Gy in 2 fractions (n=30) or 20 Gy in 4 fractions (n=20). RT efficacy was assessed with the 9-grade Sialorrhea Scoring Scale (SSS), recently prospectively validated as the most effective and sensitive tool to measure sialorrhea in ALS patients. RESULTS: At the end of RT, all patients had improved: 46 had a complete response (92% CR, SSS 1-3) and 4 had a partial response (8% PR, SSS 4-5). A significant lasting salivary reduction was observed 6 months after RT completion: there was 71% CR and 26% PR, and there was a significant SSS reduction versus baseline (P<10(-6)). There was no grade 3 to 4 toxicity, and most side effects (34%) occurred during RT. Nine patients (18%) underwent a second salivary gland RT course, with a 3-months mean delay from the first RT, resulting in a SSS decrease (-77%). Both RT dose regimens induced a significant SSS decrease with no significant toxicity. There were, however, more patients with CR/PR in the 20-Gy protocol (P=.02), and 8 of 9 patients (89%) receiving a second RT course had previously been treated within the 10-Gy protocol. CONCLUSION: Radiation therapy of 20 Gy in 4 fractions is an efficient and safe treatment for ALS patients with sialorrhea. A shorter RT course (10 Gy in 2 fractions) may be proposed in patients in poor medical condition.

Salivary glands radiotherapy to reduce sialorrhea in amyotrophic lateral sclerosis: dose and energy.

PURPOSE: This retrospective study evaluated the effectiveness of salivary gland radiotherapy for reducing sialorrhea in patients with amyotrophic lateral sclerosis (ALS). PATIENTS AND METHODS: From August 2001 to February 2008, 21 patients with amyotrophic lateral sclerosis (six men, 15 women; mean age 61.2 years, range 39-81) received external beam radiotherapy for sialorrhea (evaluation by the ALS Functional Rating Scale). All patients had previously received pharmacological treatments with unsatisfactory results or side effects. The mean dose was 19.1Gy (range 3-48), delivered in five fractions (range 1-16) on 17 days (range 1-77). Eight patients received 3D-conformal and 13 received 2D-conformal radiotherapy. Clinical target volumes included the parotids and submandibular glands (18 patients), submandibular glands and one parotid (one patient), or parotids (two patients). Thirteen patients were treated with 5.5-6MV photons and eight were treated with 6-15MeV electrons. A satisfactory salivary response was defined as complete or partial improvement. The median follow up was 10.4 months (range 0.4-26). One patient was lost to follow up. RESULTS: A positive response was observed in 65% of patients during a mean of 7 months (range 1-23). Four patients (20%) treated with photons and no patients treated with electrons experienced acute toxicity. Half (50%) the patients treated with photons and 87.5% of patients treated with electrons responded positively (P=0.09). Positive responses were more common with a high total dose (≥16Gy; 78.6%) than a low total dose (<16Gy; 33%; P=0.07). No differences were observed in tolerance (P=0.27). Age and sex did not impact the response. CONCLUSION: Salivary gland radiotherapy effectively reduced sialorrhea in patients with amyotrophic lateral sclerosis. An adequate compromise between toxicity and efficiency was achieved with 3D-conformal radiotherapy delivered with electrons to parotids and submandibular glands in a total dose of 16Gy or more (mean: 20Gy in five fractions).

Unilateral parotid electron beam radiotherapy as palliative treatment for sialorrhea in amyotrophic lateral sclerosis.

When ALS patients experience oropharyngeal weakness, sialorrhea can become a considerable challenge. Drooling has a profound negative impact in patient's quality of life causing embarrassing social situations. Several therapeutic modalities, including anticholinergic drugs, botulinum toxin injection, and radiotherapy have emerged as treatments for drooling in ALS. This retrospective case series study examined the effect of palliative radiotherapy in controlling problematic oral secretions in 10 ALS patients refractory to medical management. External electron beam radiation was targeted to a single parotid gland unilaterally with a total dose of 1500 cGy in 3 fractions at a depth determined by CT scanning. One patient received additional radiotherapy to the contralateral parotid due to persistent secretions. All patients reported improvement with a reduction in the intensity and amount of drooling. In 5 of 10 patients, anticholinergics were discontinued and were reduced in another two. There were no major side effects of treatment. We conclude that unilateral parotid electron radiotherapy provides satisfactory relief from sialorrhea in ALS patients and should be considered as a therapeutic option for patients who are refractory to medical management.

Comparison of radiotherapy types in the treatment of sialorrhea in amyotrophic lateral sclerosis.

OBJECTIVES: Many patients with amyotrophic lateral sclerosis (ALS) develop progressive difficulty swallowing secretions, leading to drooling. Although external beam radiation is considered to be an effective and well-tolerated treatment, the optimum schedule in terms of dose, target, radiation type, and number of fractions is unknown. The aim of this observational study was to define the most effective schedule for salivary gland irradiation and to compare electron and photon radiotherapy. METHODS: Sixteen patients with ALS (12 females and 4 males) with drooling, enrolled for external radiation of salivary glands between 2002 and 2007, were included. Patients received different treatment protocols according to the decision of their radiotherapist. Efficacy and safety were assessed at 1 and 6 months after treatment by a neurologist and a radiotherapist using a 4-point Likert patient improvement scale, as follows: 0 (no change), 1 (slight improvement), 2 (good improvement), and 3 (very good improvement). RESULTS: Radiotherapy for drooling was shown to be safe and effective in ALS patients with duration of effect expected up to 6 months. Eighty percent of patients felt improved at 1 month and 43% at 6 months after external radiation. Patients with sustained improvement at 6 months were treated with electron therapy (>8 MeV; p = 0.02). CONCLUSIONS: Electron-based radiotherapy, delivered as five 4Gy fractions to a total dose of 20 Gy, encompassing the whole of the submandibular gland and sparing the upper part of the parotid gland, can be proposed as a safe and effective schedule for the treatment of sialorrhea in patients with ALS.

Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: multidisciplinary care, symptom management, and cognitive/behavioral impairment (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.

OBJECTIVE: To systematically review evidence bearing on the management of patients with amyotrophic lateral sclerosis (ALS). METHODS: The authors analyzed studies from 1998 to 2007 to update the 1999 practice parameter. Topics covered in this section include breaking the news, multidisciplinary clinics, symptom management, cognitive and behavioral impairment, communication, and palliative care for patients with ALS. RESULTS: The authors identified 2 Class I studies, 8 Class II studies, and 30 Class III studies in ALS, but many important areas have been little studied. More high-quality, controlled studies of symptomatic therapies and palliative care are needed to guide management and assess outcomes in patients with ALS. RECOMMENDATIONS: Multidisciplinary clinic referral should be considered for managing patients with ALS to optimize health care delivery and prolong survival (Level B) and may be considered to enhance quality of life (Level C). For the treatment of refractory sialorrhea, botulinum toxin B should be considered (Level B) and low-dose radiation therapy to the salivary glands may be considered (Level C). For treatment of pseudobulbar affect, dextromethorphan and quinidine should be considered if approved by the US Food and Drug Administration (Level B). For patients who develop fatigue while taking riluzole, withholding the drug may be considered (Level C). Because many patients with ALS demonstrate cognitive impairment, which in some cases meets criteria for dementia, screening for cognitive and behavioral impairment should be considered in patients with ALS (Level B). Other management strategies all lack strong evidence.

Sialorrhoea and drooling in patients with Parkinson's disease: epidemiology and management.

Although often less recognized than motor symptoms, non-motor effects represent an important source of disability for many parkinsonian patients. Of these non-motor symptoms, sialorrhoea, defined as the inability to control oral secretions resulting in excessive saliva accumulation in the oropharynx, constitutes perhaps one of the most bothersome and troubling problems, often causing social embarrassment and isolation. In patients with Parkinson's disease (PD), this symptom is thought to be due to restricted swallowing and dysfunction, rather than to hypersecretion of saliva. Only a few well designed studies have been conducted to determine the optimal treatment for sialorrhoea in PD. A combination of approaches appears to be necessary to obtain successful results.

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.

Radiotherapy to the salivary glands as treatment of sialorrhea in patients with parkinsonism.

This study investigated retrospectively the long-term efficacy and safety of radiotherapy (RT) to the major salivary glands as treatment of sialorrhea in patients with parkinsonism. Twenty-eight patients received a bilateral dose of 12 Gy to the parotid and part of the submandibular glands between 2001 and 2006. Severity of sialorrhea and adverse events were assessed at 1 and 6 months post-RT and finally in the first quarter of 2007. Item 6 of the activities of daily living-section of the Unified Parkinson's Disease Rating Scale was used as primary endpoint. Quality of life (QoL) pre- and post-RT was investigated using a shortened Parkinson's Disease Questionnaire-8. Sialorrhea had improved significantly at 1 month post-RT and this effect was maintained for at least 1 year. Most frequent adverse events were loss of taste and a dry mouth; however, 75% of these adverse events were transient. QoL had improved significantly on the long term. The clinical global impression scores at the final follow-up showed that 80% of patients were satisfied. It was concluded that RT is an effective and safe treatment of sialorrhea on the long term in patients with parkinsonism.

[The current approach to hyper-sialorrhea]. / Approche actuelle de l'hypersialorrhée.

Drooling (sialorrhea or excessive salivation) is a common problem in neurologically impaired children and in adults who have Parkinson-disease. It is most commonly caused by poor oral and facial muscle control (aetiology) and worsened by some contributing factors. Treatment is best managed by a clinical team (speech pathologists, occupational therapists, dentists, otorhinolaryngologists) Treatment options range from conservative to more aggressive measures such as medication (anticholinergic medication, botulinum toxin type A injections in the glands), radiation and surgical therapy.

Controlling sialorrhoea: a review of available treatment options.

Sialorrhoea (drooling or excessive salivation) is a common symptom of many neurological diseases (e.g., amyotropic lateral sclerosis, cerebral palsy and Parkinson's disease) and otolaryngologic diseases (tumours of upper aerodigestive tract). It is mostly caused by poor oral and facial muscle control in patients with swallowing dysfunction (secondary sialorrhoea). However, some cases of sialorrhoea are due to hypersecretion of saliva. These cases represent so-called primary sialorrhoea.

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.