Production of oral secretions

Saliva is produced by six major salivary glands and several hundred minor salivary glands. The major salivary glands secrete 90% of the 1.5 L of saliva produced each day. Healthy people swallow approximately once a minute as a result of saliva pooling, although this varies with its rate of production.2 The parotid and submandibular salivary glands are relatively superficial. The submandibular and sublingual salivary glands are primarily responsible for producing background saliva throughout the day, while the parotid glands’ primary function is to secrete saliva during periods of olfactory, gustatory and tactile stimulation.3 These differences in salivary gland function may be clinically significant, as determining the timing of a patient’s saliva problem may allow targeted therapy. Neural stimulation of salivary production is parasympathetic, whereas contraction of salivary duct smooth muscle is stimulated by the sympathetic nervous system. Stimulation of beta-adrenergic receptors is responsible for the production of mucoid secretions. Oral secretions have several important physiological functions. Saliva protects oral tissue, lubricates food for swallowing and contributes to maintaining good dental health. Saliva and mucoid secretions form a vital part of a patient’s barrier immune system.4

Sialorrhoea and its symptoms

Sialorrhoea is an inconsistently used term most commonly describing excessive serous saliva in the mouth that can result from hypersecretion of saliva, anatomical abnormalities or facial–bulbar weakness. In neurological conditions, this excessive saliva results from weakness or poor coordination of bulbar or facial musculature. This leads to ineffective swallowing mechanics, reduced swallowing frequency, poor lip seal and ineffective saliva control, but not excessive production of saliva.1 5 6 Sialorrhoea commonly affects adults with various neurological conditions including stroke; neuromuscular diseases such as amyotrophic lateral sclerosis/motor neurone disease and neurodegenerative diseases such as Parkinson’s disease, multiple system atrophy, progressive supranuclear palsy and dementia with Lewy bodies. Although it is often stated that autonomic dysfunction in Parkinson’s disease causes hypersalivation contributing to the sialorrhoea, studies into salivary production in this condition show reduced or normal salivation compared with controls.5 7

Estimates of the prevalence of sialorrhoea in those neurological conditions most commonly associated with this symptoms are as follows: Parkinson’s disease 10%–84%;5 motor neurone disease 20%–40%8 and cerebral palsy 20%–58%.9 10

Physical consequences of sialorrhoea include excoriation of the skin around the mouth, speech and sleep disturbance, dehydration and increasing fatigue. These physical problems are also associated with psychosocial symptoms such as embarrassment and social withdrawal.11 In many patients with neurological disease these symptoms will be accentuated by muscle weakness or dystonia in the neck, trunk or limbs causing a flexed posture and/or difficulties maintaining oral hygiene. Saliva may also pool at the back of the throat, causing coughing and a higher risk of aspiration.12 There are reports of pooling of saliva affecting patient’s ability to use non-invasive ventilation, which in neuromuscular diseases—particularly motor neurone disease—is an intervention that improves the quality of life and survival.13

Tenacious saliva and thick secretions

The burden of problematic thickened secretions is also poorly defined. It is important to recognise that patients with sialorrhoea may also have thickened secretions collecting in their mouth and throat, often resulting from treatments for sialorrhoea. Thick secretions can lead to chewing and swallowing problems and can also impact on the tolerance of non-invasive ventilation.14 15

Conservative measures

Although there is little evidence confirming their effect, there are various available conservative measures for managing sialorrhoea and associated symptoms. The appropriate use of these conservative managements will vary between patients.

Neck collars and head-back wheelchairs are useful devices to improve positioning and counteract a flexed posture. This simple measure is likely to improve patients’ comfort and self-image. Speech therapy should be involved early, aiming to maximise the patient’s swallowing function and lip seal. Oral prostheses, trialled in neurologically impaired patients to improve lip seal, improve quality of life.22 For patients with Parkinson’s disease, reduced oral sensation or cerebral pathology, swallow reminders may help.6

Several oro-rehabilitation approaches have also been used in neurologically and cognitively impaired children with success. These include oro-motor therapy, biofeedback or behavioural interventions.23

Portable suction devices can be considered in patients with treatment-resistant symptoms, particularly if they have pooling of saliva in the throat. While these devices are portable they are not necessarily discrete and patients may find using them embarrassing (figure 2).

• Download figure
• Open in new tab
• Download powerpoint

Figure 2

Portable suction unit.

Anticholinergics

Anticholinergics are a group of drugs that inhibit the action of the neurotransmitter acetylcholine at muscarinic receptors, thus reducing saliva production. Care must be taken when using anticholinergics not to cause an excessively dry mouth. This may be more distressing for the patient than their original problem and can contribute to poor oral hygeine.24 25 There are various anticholinergics and drugs with anticholinergic effects that are used to manage sialorrhoea, including hyoscine hydrobromide, atropine, glycopyrrolate, tropicaimide, hyoscyamine sulfate and the tricyclic antidepressant amitriptyline (table 2).5 20 26 However, there is only limited evidence supporting these drugs as effective interventions, with only a few studies carried out across a range of diseases.27

Unfortunately, these medications are not specific to the muscarinic receptors of the salivary glands.25 Patients using these medications for sialorrhoea management risk unwanted effects in other organ tissues. These effects include urinary retention, constipation, increased intraocular pressure, cessation of perspiration with increased body temperature and double vision. Moreover, anticholinergics can affect the central nervous system causing adverse effects such as confusion, disorientation, memory problems, sedation and nausea, which can often be intolerable, especially in the elderly.24 25 The topically applied hyoscine patch can also cause skin irritation that is often severe enough that it has to be stopped.28

Botulinum toxin

Botulinum toxin is a neurotoxin produced by the bacterium Clostridium botulinum. It has been used since the 1980s to treat conditions such as strabismus and dystonia. There are seven types (A–G) that work by penetrating the axon terminals and degrading synaptosome associated protein (SNAP)-25 proteins, preventing neurosecretory vesicles fusion with the nerve synapse plasma membrane.31 32 Both botulinum toxin A and B have been used to manage sialorrhoea (t able 3).33

Radiotherapy

External beam radiotherapy using photons or electrons is an alternative method for controlling sialorrhoea. It is usually used following the failure to respond to or tolerate treatment with anticholinergic drugs and botulinum toxin. There are several retrospective and prospective studies, carried out in patients with Parkinson’s disease and motor neurone disease, reporting objective reductions in saliva production and improvements in patient symptoms.34 While these studies did not include control groups, the same patients had previously failed to achieve symptom control with other available treatments for sialorrhoea. As with botulinum toxin injections, there is no consensus about the optimal dosing regimen for salivary gland irradiation to treat sialorrhoea. Most commonly used regimens target both submandibular glands and the caudal two-thirds of both parotid glands. Studies to date have used a range of doses, with a median dose per fraction of 5 Gy (0.83–8 Gy) and a mean total dose of 12 Gy (3–48 Gy). The length of the effect of radiotherapy is variable and was reported to last for several months to 5 years, with around half of patients still experiencing effects at 6 months.

Radiotoxicity can occur resulting in an overly dry mouth with more viscous saliva, facial erythema, pain and nausea.34 These effects are usually short lived and the risk of their development is likely to be reduced with new techniques, such as CT mapping which allows for highly localised therapy.35 Because many of the patients with neurological disease have a short life expectancy, there is less concern about malignancy; however, in those with longer life expectancy this may be an unnecessary risk.

Surgical options

There are some effective surgical interventions for sialorrhoea. Options include removing the submandibular or parotids salivary glands, relocating or ligating the submandibular and/or parotid duct and transtympanic neurectomy.36 These surgical interventions have most commonly been used in neurologically impaired children with symptoms resistant to medication and botulinum toxin. Using surgery to manage sialorrhoea in older patients is rare and would only be considered after less-invasive approaches have failed.

Meta-analysis of surgical options suggests that bilateral submandibular duct rerouting, bilateral submandibular gland excision with bilateral parotid duct rerouting and bilateral submandibular gland excision with bilateral parotid duct ligation appear to be of similar efficacy.36 While potentially less effective, four-duct ligation offers a simple, quick and safe procedure that may improve symptoms.37

Many patients with motor neurone disease, Parkinson’s disease and other neuromuscular and neurodegenerative disorders do not have the functional reserve to tolerate surgical intervention. Additionally, life expectancy is often short and so there is less need for interventions that will work for many years.