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

doi:10.1016/S0022-510X(01)00631-1

Journal of the Neurological Sciences

Volume 191, Issues 1–2, 15 October 2001, Pages 111-114

https://doi.org/10.1016/S0022-510X(01)00631-1 Get rights and content

Abstract

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.

Introduction

Drooling and subjective sialorrhea are common in amyotrophic lateral sclerosis (ALS) patients with facies–lingual–pharyngeal paresis, in particular in the later stages of the disease when severe paresis can develop. The symptoms can cause considerable social embarrassment and discomfort, difficulty in speaking, produce foul odors and increase the risk of aspiration pneumonia.

A wide range of different methods has been tried to alleviate drooling in patients with bulbar paresis. Commonly used medication is anticholinergic treatment often in the form of atropine tablets or mixture, nebulized scopolamine [1] or scopoderm transdermal patch [2]. A disadvantage of anticholinergic drugs is their side effects, which can become pronounced especially in elderly patients. Oral glycopyrrolate at 0.4 mg thrice daily has been suggested as an alternative, its chief advantage is that it does not cross the blood–brain barrier [3], [4]. Recently, injection of botulinum toxin into the parotid glands has been tried in five bulbar ALS patients with satisfactory results [5]. Several surgical procedures have been tried to reduce drooling including simple unilateral tympanic neurectomi, excision of one or more of the major salivary glands, laser intraductal photocoagulation of the parotid ducts [6], transposition and rerouting of the ducts [7], intraoral bilateral submandibular and parotid duct ligation [8], or a combination of these procedures [9].

We have tried several of these options in ALS patients with mixed results. Although the drug treatment is often successful initially, as bulbar paresis progresses, the increasing doses needed to relieve symptoms causes unacceptable side effects. The invasive surgical procedures are not without risk of complications including xerostomia necessitating the administration of artificial saliva. Borg and Hirst [10] reported beneficial effect of radiotherapy for treating sialorrhea in 31 patients with various diagnosis including two cases with motor neuron disease, some patients developing long-term side effects.

We have therefore investigated other options and now present the results of a prospective pilot study of lenient low-dosage radiation therapy in the management of drooling in ALS.

Section snippets

Patients and methods

Eighteen ALS patients with severe drooling and a life-expectancy of less than 2 years (based on previous disease history) were included. Ten were females and eight were males. Their mean age at the time of radiotherapy was 62.3 years, and the mean disease duration 22 months. At the time of inclusion, the patients were severely disabled with a score ranging from 14/40 to 6/40 on the ALS Functional Rating Scale [11] and fulfilled rigorous criteria for probable or definite ALS [12]. The patients

Results

The mean parotid salivary secretion rate was 0.29 ml/min (varied from 0.04 to 1.08 ml/min) before irradiation. The parotid salivary secretion diminished significantly 1 day (43%) and 2 weeks (57%) after irradiation (Table 1).

Subjectively, the patients reported diminished drooling beginning 12–24 h after radiation therapy. One patient reported no effect of the therapy.

For all patients, the caregivers noted diminished salivary secretions and no aspiration pneumonia. Anticholinergic treatment

Discussion

The oral–pharyngeal secretions are a combination of secretions from the salivary glands in the oral cavity, from the nasal glands, and from the mucosa in the pharynx, larynx and lower airways. The daily salivary secretion is estimated to be 500–600 ml with large individual variations [13]. Unstimulated saliva secretion rate in healthy individuals is reported to be 0.3 ml/min for whole saliva and 0.04 ml/min from each parotid gland [13].

The parotid glands normally contributes 20% of the total

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Cited by (68)

Prevalence of Sialorrhea Among Amyotrophic Lateral Sclerosis Patients: A Systematic Review and Meta-Analysis
2022, Journal of Pain and Symptom Management
Citation Excerpt :
At last, sialorrhea in ALS is currently treated as follows. According to the national ALS Patient CARE database, the ALS patients with mild-to-moderate drooling may be easier to benefit from atropine, glycopyrrolate, or amitriptyline39,40 than the ALS patients with severe drooling because of some side effects of using anticholinergic drugs, such as urinary retention, cutaneous reactions, blurred vision and other adverse reaction.34,39,41,42 Therefore, when anticholinergic drugs may not valid for the ALS patient with severe drooling, botulinum neurotoxin (BoNT) injected into the salivary glands, radiation therapy (RT),surgical options and neurectomy are also a option to choose.43
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative motor neuron disease (MND), and sialorrhea is a known symptom in patients with ALS, which may cause a social embarrassment and discomfort. However, people do not pay attention to sialorrhea up to now. This study is aimed at conducting a systematic review and meta-analysis of the pooled prevalence of sialorrhea in ALS patients all around the world and raising awareness of salivation.
We searched PubMed and EMBASE databases to obtain the comprehensive literatures which reported the prevalence of sialorrhea. We used AHRQ and NOS to evaluate the literature quality. Subgroup analyses were performed based on screening instruments and severity of sialorrhea. At the meantime, sensitivity analyses was also conducted to identify the source of heterogeneity.
A total of 17 eligible studies which included 21 groups of data reported prevalence of sialorrhea. The pooled prevalence of sialorrhea among ALS patients was 30.8% (95% CI: 20.0%–44.2%). For studies using ALSFRS-R, direct questioning, postal survey, and ALSSoL average and ALSFRS-R, the pooled prevalence of sialorrhea was 22.7%, 25.8%, 29.8% and 52.0% respectively. According to the severity of sialorrhea, the prevalence of mild, moderate, and severe sialorrhea were 25.1%, 11.2%, and 10.5%, respectively. And none of the studies alone had a significant effect on the overall prevalence of sialorrhea after we eliminated each study separately in sensitivity analyses.
Sialorrhea is a relatively common symptom in ALS patients with a comparatively high prevalence. In our study, we found that the prevalence of sialorrhea in ALS patients is relatively higher than the results based on direct questioning or postal survey. Therefore, we deduced that sialorrhea should be evaluated by more complex professional assessment scales to improve the quality of life and improve early prognosis of disease.
Symptom Management and End-of-Life Care in Amyotrophic Lateral Sclerosis
2015, Neurologic Clinics
Managing excessive saliva with salivary gland irradiation in patients with amyotrophic lateral sclerosis
2015, Journal of the Neurological Sciences
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.
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.
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.
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
2014, International Journal of Radiation Oncology Biology Physics
Citation Excerpt :
In addition, we showed in the same study that patients with severe salivation (SSS score, ≥6) were poorly discriminated by other scales such as the Oral Secretion Scale or ALSFRS (12). Various schedules of RT have been reported, ranging from 4 to 48 Gy (4-8, 16, 17). A single low-dose (7-Gy) fraction was suggested to be as effective as higher total dosage in drooling reduction (5-7).
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.
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.
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.
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
2013, Cancer/Radiotherapie
Citation Excerpt :
However, amyotrophic lateral sclerosis is a rare disease, and radiotherapy for sialorrhea is typically proposed only after failure (and/or toxicity) of other treatments. Thus, this group of patients is one of the largest in the current literature [10,12–15]. Moreover, in a prospective series of nine patients, Harriman et al. described the difficulty of recruiting patients that presented the studied symptoms; however, they explained that a subjective evaluation of these patients was valid [14].
This retrospective study evaluated the effectiveness of salivary gland radiotherapy for reducing sialorrhea in patients with amyotrophic lateral sclerosis (ALS).
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 19.1 Gy (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 5.5–6 MV photons and eight were treated with 6–15 MeV 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.
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 (≥ 16 Gy; 78.6%) than a low total dose (< 16 Gy; 33%; P = 0.07). No differences were observed in tolerance (P = 0.27). Age and sex did not impact the response.
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 16 Gy or more (mean: 20 Gy in five fractions).
L’objectif de cette étude rétrospective était d’évaluer l’efficacité de la radiothérapie des glandes salivaires pour réduire l’hypersialorrhée chez les patients atteints de sclérose latérale amyotrophique.
Entre août 2001 et février 2008, six hommes et 15 femmes âgés en moyenne de 61,2 ans et atteints de sclérose latérale amyotrophique ont été irradiés pour une hypersialorrhée (évaluée par l’ALS Functional Rating Scale). Tous les patients avaient auparavant reçu des traitements pharmacologiques avec un résultat insuffisant ou des effets secondaires. Une dose moyenne de 19,1 Gy (3–48) a été délivrée en cinq fractions (1–16) sur 17 jours (1–77). La radiothérapie était conformationnelle tridimensionnelle pour huit patients et bidimensionnelle pour 13. Les volumes cibles cliniques comprenaient les parotides et les glandes sous-maxillaires (18 patients), les glandes sous-maxillaires et une parotide (un patient), ou les deux parotides (deux patients). Treize patients ont été irradiés avec des photons de 5,5 à 6 MV et huit des électrons de 6 à 15 MeV. Une réponse salivaire satisfaisante a été définie comme une amélioration complète ou partielle. Le suivi médian était de 10,4 mois (0,4–26). Un patient a été perdu de vue.
Une réponse a été observée chez 65 % des patients durant en moyenne sept mois (1–23). Une toxicité aiguë a été observée chez quatre patients (20 %) irradiés par photons, et chez aucun des patients irradiés par électrons. La moitié (50 %) des patients irradiés par photons et 87,5 % des patients irradiés par électrons ont bénéficié d’une réponse (p = 0,09). Les réponses ont été plus fréquentes avec une dose de 16 Gy ou plus (78,6 % contre 33 % ; p = 0,07). Il n’a pas été observé de différence de tolérance (p = 0,27). L’âge et le sexe n’ont pas eu d’incidence sur la réponse.
La radiothérapie des glandes salivaires réduit efficacement l’hypersialorrhée chez les patients atteints de sclérose latérale amyotrophique. Un compromis adéquat entre la toxicité et l’efficacité a été obtenu avec la radiothérapie conformationnelle tridimensionnelle, délivrée par électrons dans un volume incluant les glandes parotides et sous-mandibulaire à une dose totale d’au moins 16 Gy (20 Gy en cinq fractions en moyenne).
Botulinum neurotoxin type A in the interdisciplinary treatment of sialorrhea in adults and children—update and practice recommendations
2023, Frontiers in Neurology

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

Abstract

Introduction

Section snippets

Patients and methods

Results

Discussion

J. Pain Symp. Manage.

J. Pain Symp. Manage.

Otolaryngol.-Head Neck Surg.

Int. J. Radiat. Oncol. Biol. Phys.

J. Neurol. Sci.

J. Neurol. Sci.

JADA

Reduction of salivary flow in amyotrophic lateral sclerosis with scopoderm TTS

Head Neck

Use of enteral glycopyrrolate in the management of drooling

Palliative Med.