Difficulty handling saliva is a common problem in ALS. To see what can be done about it, we talked with Ashok Verma, an associate professor of neurology at the University of Miami School of Medicine, who sees patients at the Kessenich Family MDA/ALS Center at the University of Miami.
Q: What causes excess saliva and drooling in ALS?
A: (Ashok Verma) In ALS, there is no problem with saliva production. Saliva production is normal; it's the handling of saliva that is not normal.
Q: What do you mean by the handling of saliva?
A: The saliva can't be handled when there is weakness of the tongue and throat muscles. Drooling can be an early and significant symptom when ALS involves these muscles early, as in the bulbar type of ALS. It also depends to some extent on the anatomical structure in each person. For example, elderly patients with a small mandible [lower jawbone] and poor dental architecture may start drooling very early. Other people can handle the saliva better.
Q: How do we normally handle saliva?
A: Saliva is normally secreted by three major pairs of salivary glands and numerous minor glands in the mouth cavity. Saliva is needed to moisten the mouth cavity and to help with swallowing and digesting food. It is poured in copiously (at about a fivefold increase) when we smell, taste, chew and swallow food. Some secretions also come up through the respiratory tree, as part of the protective mechanisms that we all have. Saliva comes in two parts — thin, watery secretions and thick, mucus-containing secretions.
Q: What happens in ALS?
A: Some people have a lot of drooling, also called sialorrhea. But others complain more of phlegm sitting in the throat. They can't swallow it, and they can't cough it up because of weak muscles.
In ALS, you can have weak muscles around the mouth, tongue, throat and so forth. This compromises the handling of saliva in the mouth and the swallowing mechanism. Sensation is normal in ALS, so patients know that secretions are sitting in the mouth and building up, and that they're drooling.
The drooling is more from the thin, watery saliva, and that's what we are attempting to aim at with pharmacotherapy [drugs].
Q: How do you treat the excess saliva or drooling?
A: In the beginning, with ALS, there isn't that much sialorrhea. However, many patients are on antidepressants, and we try to give them antidepressants that have the side effect of dryness of the mouth. We take advantage of that side effect with the tricyclic type of antidepressants. [Some examples of these are amitriptyline (brand name Elavil), imipramine (Tofranil) and clomipramine (Anafranil).]
In some patients, we use a scopolamine patch, which is usually used for motion sickness. [The patch is applied to the skin. A trade name is Scopoderm.]
All these agents block the action of acetylcholine, which comes from the nervous system and normally gives a "kick" to the salivary glands to produce saliva. [Acetylcholine is a neurotransmitter, a chemical that carries signals between the nervous system and other organs.] The glands are still intact, and not all the saliva is gone. Up to approximately half the saliva production is knocked down in patients who can tolerate these medications. These are mild drugs, and their side effects are mild.
If tricyclic antidepressants and scopolamine are not effective, the next step is to go to more potent drugs like Robinul [generic name glycopyrrolate]. These drugs block acetylcholine wherever it is in the system, and they can cause constipation, urinary hesitancy and impaired potency.
Drugs such as Robinul can also worsen glaucoma if people already have it and can increase urinary obstruction if people have an enlarged prostate gland. They can worsen confusion in people with memory loss. Patients in a humid environment may feel a little more discomfort because of decreased sweating. [All these symptoms are from blockade of acetylcholine.]
Some patients have more side effects than others. We start with a small dose.
Q: If those medications don't help, what's next?
A: Some people don't tolerate these medicines because of side effects, and in some people they're just not effective. Then we go further.
At our center, the next step is injection of botulinum toxin, which comes from the bacterium Clostridium botulinum. It works in the same way as the medications, by blocking acetylcholine release from nerve endings but only at or near where it's injected. We use injections of Botox. [Botox is a brand name for botulinum toxin type A, and Myobloc is the brand name for botulinum toxin type B. They're similar substances.]
|Three major, paired glands — the parotids, submandibulars and sublinguals — and numerous minor glands throughout the mouth (not shown) normally produce saliva. Injecting botulinum toxin (Botox or Myobloc) into the partoids is one strategy for reducing saliva and controlling drooling in ALS.
I inject Botox into each parotid gland. The parotids are the major glands for the thin, watery part of the saliva. These glands are accessible just below the skin at the angle of the mandible. The problem with Botox is that if it's injected at the wrong site or if it travels, it can block muscles in the area and increase dysphagia [difficulty swallowing] and dysarthria [difficulty speaking].
I inject it directly, by pinching the parotid gland between the thumb and index finger. Some people have injected Botox into the parotid by going into the duct from which the secretion is coming, but there are reports of side effects with that method, such as swelling and dramatic inflammation of the gland.
You have to be careful to inject it at the right place and in the right amount, but it's pretty simple. I do it myself or have a neuromuscular specialist working under me do it. You don't need a surgeon to do it.
It takes a week to 10 days for the maximum effect to be seen. In about two weeks, you know whether or not it has worked. If it hasn't, after about three weeks, I inject a little more Botox on both sides.
Depending on the response, you can go in a second or third time. My overall impression, based on the patients I have treated, is that saliva production is knocked down by about 50 or 60 percent in about half the patients with a dose of Botox. With a second or third injection, it's effective in about 75 percent of patients.
Q: How do you know whether a treatment for sialorrhea is working?
A: We're doing research here with Botox and have a protocol for the quantitative assessment of sialorrhea. It involves counting how many tissues the patient was using before and after the treatment and also the subjective report of symptoms. We also use a visual scale, in which patients put a point value, like 10 or 100, to estimate how much sialorrhea they're having.
Q: Are there other treatments?
A: In a few patients, we have used radiation of the salivary glands. We give a small dose. The idea is to damage the gland, to induce fibrosis [scarring], and that takes several weeks or months. The idea is not to knock down saliva totally but to decrease it to relieve drooling.
The problem with radiation is that it's irreversible, whereas Botox is reversible. I've only used radiation in three or four people — those who didn't respond to other treatments.
There are reports in the medical literature of surgeries that can be done on the salivary glands, but this is not generally done in ALS.
I'm aware of a dentist who has made orthotics [appliances] for some patients with cerebral palsy and sialorrhea. These orthotics increase the lip seal to keep the saliva in the mouth. They work when the swallowing mechanism is unaffected. Sometimes they can be used in ALS patients in whom the angle of the mouth may precipitate drooling. It's like a retainer to provide a better seal.
In ALS, as opposed to disorders like cerebral palsy, you're dealing with a progressive disease, and when the illness becomes more severe, there are more pressing issues. But by doing all these things we've talked about, you're able to buy some time so that the sialorrhea is not a significant symptom. Otherwise, it's a social problem and a nuisance.
Q: Do you do anything about the mucus-containing part of the secretions?
A: There really isn't a good treatment for the mucus secretions, because those don't have a major nerve supply that you can block. Some doctors have used drugs called beta blockers on the premise that these glands have beta adrenergic receptors, but I haven't seen any published report on this. [Beta adrenergic receptors are part of the nervous system, and beta blockers are drugs that block these receptors and alter some responses in the nervous system.] I think you would have to use a large amount, with potential side effects. [Examples of beta blockers are propranolol (Inderal) and metoprolol (Toprol).]
Q: How do you usually proceed in treating sialorrhea?
A: If the patient is already on an antidepressant, we switch to an antidepressant that has the side effect of drying out the mouth. If that isn't effective, we go on to scopolamine or Robinul and increase the dose if we need to. The next step is Botox and then radiation. In most patients, drooling can be controlled or at least brought to a level where it's tolerable.