Research Roundup

by Margaret Wahl

Does a high serum cholesterol level increase survival time in ALS?

A French research team that published its findings March 25 in Neurology has found that elevated levels of lipids (fatlike substances) in the blood, known to be risk factors for cardiovascular disease, actually may be a good thing in ALS.

High lipids more common in ALS group than non-ALS control group

First, Vincent Meininger at the Pitié-Salpêtrière Hospital in Paris, and colleagues, looked at lipid levels in 369 people with and 286 people without ALS.

They measured serum triglycerides, the most common form of fat in the bloodstream; cholesterol, a fatlike substance known to build up in arteries but also necessary for building cell membranes; lowdensity lipoproteins (LDL), which carry cholesterol from the liver to the rest of the body and are sometimes called “bad cholesterol”; and high-density lipoproteins (HDL), which carry cholesterol from the body’s tissues to the liver (for elimination) and are sometimes called “good cholesterol.”

The researchers found elevated total serum cholesterol levels in 24 percent of the ALS patients, compared with 11 percent of the non-ALS patients. They found elevated LDL levels in 49 percent of the ALS patients, compared with 20 percent of the control group.

ALS patients with high lipid levels survived longer

Medical records from 59 French ALS patients found having a high ratio of “bad” to “good” serum cholesterol levels was associated with living about a year longer.

They then looked at the records of 59 patients with ALS who died between 1983 and 2005 and divided them into two groups: those with low LDL/HDL ratios and those with high LDL/HDL ratios. What they found was surprising: Those with a low LDL (“bad cholesterol”) to HDL (“good cholesterol”) ratio lived an average of just over three years, while those with a high LDL/HDL ratio lived an average of just over four years.

The authors interpret their findings to mean that having an elevated ratio of LDLs to HDLs increased survival time in ALS by about a year, which suggests to them that the disease itself might be triggering a protective alteration in metabolism.

They say their findings “warn against the use of lipid-lowering drugs in this vulnerable population of patients” and that attention to adequate nutrition should be a priority in ALS care.

Study brings WHO report to mind

In an accompanying editorial, University of Pittsburgh epidemiologist Steven Albert reminds readers of a 2007 report from the World Health Organization that raises the possibility that the use of statin medications, such as atorvastatin (Lipitor), lovastatin (Mevacor) and others, which lower cholesterol levels, could increase the risk of developing ALS. (See Research Roundup, September 2007.)

Are high lipid levels the true cause of longer survival time?

Stan Appel, an MDA research grantee at Methodist Neurological Institute in Houston, where he directs the MDA/ALS Center, says the investigators are to be congratulated for their study, but it may be premature to conclude that increased LDL/HDL ratios are protective in ALS.

“Their report provides no data as to why either increased LDL, low HDL, or the increased ratio of LDL/HDL might be associated with prolonged survival,” Appel says.

“In fact, the challenge to the field is to confirm these results and then determine why the high LDL/HDL patients live longer. It may be premature to conclude, as they do in their title, that ‘Dyslipidemia [altered fat levels] is a Protective Factor in ALS.’

“A preferred title would have been ‘ALS Patients With Dyslipidemia Have Prolonged Survival,’” he says, a phrasing that doesn’t assume cause and effect but merely states an association.

“It’s also premature to warn ALS patients against the use of statins or related compounds — especially in patients with significant past cardiovascular disease, where statins are of proven therapeutic value,” Appel says.

Weighing the risks of lipid-lowering meds

These are preliminary findings, noted MDA Medical Director and Vice President of Research, Valerie Cwik.

“In the meantime, patients should not make any decisions about their diet or medications without first consulting their own physician.”

ALS-causing flaws in TDP-43 gene found in two new studies

Genetic variations could make some people particularly vulnerable to poisoning from organophosphate compounds, such as those used in some pesticides.

More cases of ALS caused by mutations in the protein known as TDP-43 have been identified, this time in France and Quebec, Canada, by a team coordinated by MDA grantee Guy Rouleau at the University of Montreal; and in a European and a Chinese family by Gerard Schellenberg at Veterans Affairs Medical Center in Seattle, and colleagues.

Rouleau and colleagues, who published their findings online March 30 in Nature Genetics, screened 200 people with ALS and 185 without the disease. They found TDP-43 mutations in six people with sporadic (nonfamilial) ALS, and three in people with familial ALS; they found none in the unaffected control group.

Schellenberg and colleagues, who published their findings online April 5 in Lancet Neurology, screened 259 patients with ALS, frontotemporal dementia (a brain disease), or both, for TDP-43 gene variations. They found two variants that correlated with inherited ALS in two families. The variations were absent in an unaffected control group. These findings further support evidence that TDP-43 gene and protein abnormalities may cause ALS. (See Research Roundup, April.)

Researchers probe possible links between genes and exposures to toxins

New findings from researchers at Massachusetts General Hospital in Boston and the University of Washington-Seattle have unexpectedly contradicted earlier reports that suggested variations in an enzyme called PON1 (paraoxonase 1) might underlie susceptibility to illness, including ALS, from exposure to organophosphate-based pesticides and other potentially toxic substances. (See the Research Roundup in the April issue and “ALS and Vets” in the March issue.)

An elevated incidence of ALS in veterans of the Persian Gulf War has been observed, and a combination of PON1-related genetic susceptibility and exposures to pesticides and antinerve gas medications has been proposed as its cause.

However, when Anne-Marie Wills at Mass General, and colleagues, analyzed blood samples from 140 people with ALS and 153 without the disease, they were surprised to find there was no significant difference in the two groups in either the amount of PON1 enzyme or its ability to break down organophosphates, even though a particular variant of the PON1 gene and enzyme was more common in the ALS group than in the non-ALS group.

Robert Brown, director of the MDA/ALS Center at Mass General, and Merit Cudkowicz, a longtime MDA ALS research grantee, were on the study team, which published its findings in the March 18 issue of Neurology.

Elsewhere, a different research group has found mutations in another gene, one that also has connections to organophosphates, also causes a disease of the motor neurons (the nerve cells affected in ALS).

Shirley Rainier at the University of Michigan and her colleagues, who published their findings in the March issue of the American Journal of Human Genetics, identified mutations in the neuropathy target esterase (NTE) gene in two families with a form of motor neuron disease. The disorder resembled neurologic symptoms of chronic organophosphate poisoning.

Organophosphates are known to interfere with the NTE enzyme and/or cause it to take on toxic properties. None of the affected family members had knowingly been exposed to these chemicals, however.

“Each affected subject had two mutant NTE genes,” said John Fink, a neurology professor at the University of Michigan and senior investigator on the study. “In our patients, we think it is the NTE mutations alone that caused the motor neuron disease. We speculate, however, that individuals who have only one NTE gene mutation may be vulnerable to neurotoxic organophosphate compound exposures.”

Fink said one implication of the NTE findings is that together with PON1’s association with ALS, there is now further support for the theory that neurotoxic organophosphate compounds cause motor neuron disease in general and ALS in particular; and that genetic variations, such as in PON1 and NTE, could lower the threshold for organophosphate neurotoxicity.

People with ALS sustain hope with variety of strategies

Robert Miller, director of the MDA/ALS Center at California Pacific Medical Center in San Francisco, was part of a group of researchers who recently surveyed 16 people with ALS to assess their ability to maintain hope in the face of a devastating illness. (Hope can be defined as the belief that one can find and use pathways to reach desired goals.)

The investigators, who published their findings in the May-June issue of the Journal of Palliative Medicine, found people used a variety of approaches to sustain hope. Among them were maintaining belief in a cure for the disease, relying on spiritual beliefs, adapting to changing capacities, living in the moment and “transcending the self,” which the researchers describe as placing less emphasis on external definitions of self and a greater sense of connection with one’s past and with future generations.

The 16 study participants (13 men and three women, with an average age of 54) were, for the most part, able to remain hopeful, and their level of hope was not correlated with their projected survival time or degree of physical disability.

A Long and Winding Road

The year in research
by Margaret Wahl

The road to ALS treatment development has been long and hard. But MDA, along with the National Institutes of Health (NIH) and pharmaceutical companies, is finding there are more frequent signposts.

Among the most interesting developments of this year is the finding in a 44-person study in Italy that lithium carbonate, used to treat bipolar disorder, may have slowed the course of ALS when combined with riluzole.

Sixteen trial participants were randomly selected to receive riluzole plus two daily doses of lithium, while the remaining 28 were randomly assigned to receive riluzole only. After 15 months, about a third of those who took riluzole alone had died; all those taking riluzole and lithium had survived. The disease had progressed markedly in the riluzole-only group, but very slowly in the riluzole-plus-lithium group. An MDA-supported trial of lithium designed to test these findings is on the drawing board.

Also of note are two 2007 studies of all the DNA of a group of people with sporadic (noninherited) ALS and all the DNA of a group of people without the disease (“whole-genome association” studies). One, which had MDA support, showed at least one statistically significant difference, in a gene whose function so far is unclear. The other, which had NIH support, found no significant differences.

Scientists have concluded that, whatever the causes of ALS may be, they’re highly unlikely to include a clear genetic “smoking gun” and are more likely to reflect a combination of genetic variants and other factors.

In January, a Mayo Clinic and University of Miami study employed a narrower approach to a genome association analysis, examining only genes involved in various pathways, such as “axon guidance,” the development and maintenance of nervous-system “wiring.” When 128 of these genes were compared in people with and without ALS, the differences were significant.

Since the finding that Gulf War veterans have a higher than average rate of ALS, new research has implicated exposures to organophosphate pesticides and drugs that were given to military personnel to protect them from nerve gas attacks.

Evidence first pointed to a combination of such exposures and genetic variations in a gene for a detoxifying enzyme called PON, because people with ALS are more likely to have a particular PON variant than are unaffected people. However, a more recent finding has shifted attention to variations in a gene for a different enzyme, NTE, as a possible contributor to ALS when combined with toxic exposures.

Also this year, the MDA-supported ALS Therapy Development Institute in Cambridge, Mass., has focused on “gene expression” studies to help understand the ALS disease process. Gene expression refers to how active a gene is (how much protein is being made from its instructions).

The Institute, funded through MDA’s Augie’s Quest, is now analyzing data from a gene expression “profile” in ALS-affected mice and is starting to put together a profile for ALS-affected humans using tissue samples.

ALS TDI investigators also have uncovered variations in ALS-affected mice that may explain why drugs that showed promise in these mice frequently failed when tested in people.

These so-called SOD1 mutant mice have multiple copies of mutated SOD1 genes, which cause about 1 percent to 3 percent of human ALS cases.

The investigators found, for example, that the number of mutated gene copies, which has a profound effect on the severity of the disease, varies among these mice. Especially in experiments with small numbers of mice, the chance occurrence of an excess of low-copy-number mice in the treated group and of high-copy number mice in the untreated group could make it appear that a useless drug has a positive effect.

Current experiments at the ALS TDI are using mice with standardized gene copy numbers to minimize misleading results.

“This year of ALS research has had its successes and disappointments,” said Sharon Hesterlee, MDA’s Vice President of Translational Research. “But I think we’ve uncovered some fundamental new directions to pursue, particularly with respect to narrowing the search for ALS-related genetic differences and in ensuring that mouse studies are as predictive of clinical trial outcomes as they can possibly be.

MDA Puts ALS in the Public Eye

To promote the 17th annual national ALS Awareness Month this May, MDA has planned a number of national and local events designed to increase public awareness of ALS.

Nationally

Just in time for ALS Awareness Month is the recently updated and redesigned “Facts About ALS” booklet.

Throughout May, “ALS: Anyone’s Life Story,” will be featured on MDA’s ALS Division Web site (www.als-mda.org) and the Association’s main site (www.mda.org). This interactive feature highlights the stories of 31 individuals with ALS in 23 states — a new person each day of the month. Local media have been alerted that these individuals living in their areas have important stories to tell.

Also on the MDA Web site, special ALS Awareness Month chats will be held during May, in addition to the regularly scheduled “Living with ALS” chats.

MDA is releasing two publications and an emergency health information organizer in May. The publications include the new MDA ALS Caregiver’s Guide and an updated version of the booklet “Facts About ALS,” with new information about research and clinical trials. This booklet is a user-friendly introduction to ALS for friends, family, healthcare workers and others.

The bright yellow emergency health information envelope, available at your local MDA office, keeps important documents and information posted on the refrigerator, readily available for emergency hospital trips or 911 calls.

Locally

MDA-sponsored events around the country are designed to offer support to those coping with ALS, and information to the general public about the disease. Below is a sampling of local events; contact your local MDA office to learn out about events in your area by calling (800) 572-1717.

Atlanta

May 21 is “ALS Awareness Night” at Turner Field. Families affected by ALS and local MDA sponsors can purchase tickets for half-price to see the Atlanta Braves take on the New York Mets. During the game, awards will be presented to Kroger grocery employees with the top Shamrocks Against Dystrophy sales. As people arrive for the game, Atlanta Fire Departments will Fill-the-Boot for ALS research. Since it’s also “Harley-Davidson Owners Group Night,” H.O.G. members will ride from the Harley-Davidson dealership to the stadium, and the 100 top fundraisers will ride in a pre-game parade around the warning track. On May 3, the seminar “ALS Research 101,” will be held at the Sheraton Gateway Hotel Atlanta Airport, focusing on new trends in ALS research with a guest speaker from the ALS Therapy Development Institute in Cambridge, Mass. For more information, call Vicki Cunneen at (770) 621-0355.

Baltimore

“MDA/ALS Spring Fling Picnic,” an evening of ALS awareness and family fun for the local ALS support group, will be held at Keswick Home on May 8. Food and entertainment will be provided. May 18 is “ALS Awareness Day” at Camden Yards, when the Orioles take on the Washington Nationals. Various ALS-awareness activities will be held at the ball park. For more information, call Laurel Gaffney at (410) 494-7106.

Boston

A three-mile ALS Walk will be held at Arthur Fiedler Field near the Hat Shell on May 18. For more information, call Mary Leeman at (508) 898-3375.

Columbus, Ohio

“Management of ALS: a Multi-Disciplinary Approach” will be held at the Fawcett Center at Ohio State University on May 9. The seminar will welcome several speakers, including MDA/ALS Center clinic team members, equipment vendors, a hospice nurse and a national Permobil wheelchair representative. The event is free and lunch will be provided. For more information, call D. Blythe Hundley at (614) 841-1014.

Denver

“An Afternoon with the Experts,” a symposium to be held at the Denver Zoo conference area on May 2, will feature a panel of researchers discussing recent ALS research and clinical trials. MDA/ALS clinic team members will talk about nutrition and respiratory needs in ALS. Medical supply venders and other disability related businesses will have product and information displays. Call ahead for conference reservations and free tickets to the zoo. For more information, call Linda Johnson at (303) 691-3331.

El Paso, Texas

The emergency health information envelope organizes vital information.

May 9 is “Fire Fighter Appreciation, ALS Awareness Night” at El Paso Diablos’ Cohen Stadium. After the baseball game, fans are invited on the field where “Pride of the Yankees,” a movie about Lou Gehrig, will be shown on the pitcher’s mound. For more information, call Thelma Herrera or Kathleen Born at (915) 584-6355.

Honolulu

At Queen’s Conference Center on May 3, the 8th annual ALS seminar will feature a variety of guest speakers who provide community resources to families affected by ALS, including MDA/ALS clinic team members and representatives from medical vendors and government services. The seminar also will feature breakout rooms focused on medical care, finance, law, insurance and travel. For more information, call Jennifer Li at (808) 593-4454.

Los Angeles/Southern California

“CommUNITY for a Cure,” a seminar that focuses on community involvement to spread ALS awareness, will be held at the Evangelical Christian Credit Union (ECCU) in Brea on May 3. The event will promote the UCLA MDA/ALS clinic and new support groups, and will feature keynote speakers and equipment vendors. Also during the seminar, three Los Angeles-area individuals with ALS will be recognized for their outstanding community involvement since learning they have ALS. During the provided lunch, “The Sky’s the Limit” balloon launching ceremony will take place to raise public awareness of ALS. The names of individuals living with ALS and those who have died as a result of the disease will be written on note cards, then attached to blue balloons and released. For more information, call Andi Sass at (310) 450-9032.

New ALS Caregiver’s Guide Released This Month

by Christina Medvescek

The new Caregiver’s Guide includes myriad tips and techniques in numerous areas, including personal care.

MDA is proud to announce publication of the new MDA ALS Caregiver’s Guide. Free to those with ALS who are registered with MDA, the 210-page book replaces MDA’s 1997 ALS caregiver’s guide, When a Loved One Has ALS.

The book provides ALS caregivers with practical information on such topics as respiration, nutrition, communication, financial and legal affairs, sources of help, daily care and end-of-life issues. In addition, it’s liberally sprinkled with quotes imparting the wisdom and perspectives of experienced ALS caregivers and people with ALS.

The following excerpt from Chapter 2: Daily Care of Your Loved One with ALS offers a taste from the banquet of information available in the guide. Call (800) 572-1717 to contact your local MDA office and request a copy.

Topics in Chapter 2 include:

Below are some selected topics from Chapter 2.

Ears

People with ALS sometimes report a feeling of the ears being plugged, as if they have water in them or need to “pop.” Check with a doctor to rule out infection, sinus problems, wax buildup or other medical causes.

In the “Finding Caregiving Help” chapter, a method of organizing helpers to share the load is discussed.

In the absence of these problems, it’s possible the cause may be weakness of the muscles that maintain tone in the Eustachian tubes connecting the mouth and ear canals. In addition, weakness in the muscles that elevate the nostrils (thus opening airways) can lead to a chronic feeling of being stuffed up.

Possible remedies include “nose openers” used to stop snoring, such as Breathe Right nasal strips. These strips of tape go across the nose and hold open the nostrils. Antihistamines and decongestants sometimes help, and some say they can get their ears to pop by using their CoughAssist machine.

For some with ALS, the ears become painfully folded during side-lying. Some caregivers create an “ear pillow” to prevent this problem. Using a piece of foam of the proper thickness to keep the head in alignment (not tilted up too high), cut out a 4-inch hole in the center for the ear, and cover the foam with a pillow case.

Itchy Scalp

Some people with ALS seem to experience greater-than-normal scalp itchiness. There are a variety of possible causes, including dryness, yeast or fungus overgrowth, and stress. Check with a doctor and experiment to find the right remedy. Some things that have worked for others:

• Use gentle hypoallergenic hair care products.


• Shampoo hair in lukewarm water — hot water strips away protective scalp oils. Towel dry gently, not vigorously. Don’t wash too frequently or too infrequently.


• Use a humidifier.


• Over-the-counter remedies include Benadryl, Absorbine Jr. (applied liberally to the scalp), shampoos containing ketoconazole (such as Nizoral) or coal tar (such as T-Gel). Scalpicin Anti-Itch Scalp Treatment is a spray that can be used several times a day.


• In some cases of chronic itching or skin sensitivity, a physician may prescribe an anti-epileptic drug such as carbamazepine (Tegretol) or gabapentin (Neurontin), or one of the tricyclic antidepressants.

Neck

Neck muscle weakness in ALS makes it hard to turn or hold up the head, leading to decreased mobility and — if untreated — pain, especially when turning the head, raising and lowering into bed, or rolling over. Poor neck posture also can impair breathing, swallowing and communication. Effective management of neck weakness can prevent or treat pain and injury. The key is to find the best methods of supporting the head.

Be aware that neck weakness makes the person more vulnerable to injury during transfers and when riding in a vehicle. If the head suddenly flops down, back or to the side, muscles and ligaments in the neck can tear, or the cervical spinal cord or neck vertebrae can be seriously injured. For some, even a slight jerk is all it takes to tear muscles.

Encourage and assist neck-stretching exercises (after consulting a physical therapist). Two simple exercises:

1. Slowly turn the head to each side as far as possible without pain, hold and return to the center.

2. Tilt the head sideways on each side, so the ear points down toward the shoulder; hold and return to center.

Use a lumbar roll or cushion behind the lower back to prevent slumping when sitting, and to prevent the head and shoulders from tipping forward. Pillows under each arm also promote upright head position when sitting.

Work with a physical therapist to investigate different types of soft collars, neck braces and head supports such as a band around the forehead that attaches to a headrest. Alternating the use of collars and head support systems helps reduce pressure points and skin breakdown. Thin-cushioned skin dressings (e.g., Duoderm) also protect the skin.

Sleep Deprivation

ALS caregivers may get up numerous times a night to reposition or help their loved ones, leading to chronic sleep deprivation. Often the problem isn’t getting up, but the inability to fall back to sleep afterwards.

Strategies to get more rest include:

• Make it quick and quiet. When getting up, don’t turn on the lights (use a low-level nightlight if necessary), don’t have a conversation or do anything mentally stimulating, and stay up the minimum amount of time necessary.


• Don't try too hard. If you can’t fall back to sleep within 10 or 15 minutes, get up and do something relaxing, then return to bed as you feel yourself getting drowsy. Performing a good all-over body stretch can add in relaxation.


• Decrease caffeine, alcohol and nicotine. Especially avoid caffeine in the afternoon, as it can contribute to sleeplessness at night. Although some people find that an alcoholic drink before bed helps them fall asleep, alcohol increases the likelihood of waking later in the night.


• Power nap. Aim for a short (15- to 30-minute) nap sometime during the “midday trough” between 1 p.m. and 3 p.m., when your body naturally wants to rest. A longer nap may leave you groggy and unable to sleep at night. If you can’t fall asleep, just rest quietly with eyes closed for a brief period.


• Three on, three off. If possible, share nighttime caregiving duties. For optimum benefits, sleep experts recommend a three-nights-on, three-nights-off schedule, rather than switching with someone every other night.


• Talk to your doctor. Not all caregiver sleep problems are caused by stress or getting up in the night. Schedule an appointment if nothing else is working.

Striking Out Aspiration
A full count of strategies for protecting your lungs

by Amy Labbe

Most people don’t think about swallowing during meals or as they go about their daily lives, but many people with ALS do.

Weakness and a lack of coordination of the tongue and throat muscles can result in swallowing difficulty (dysphagia), causing choking on foods or liquids, drooling, the sensation that there’s excess saliva in the mouth or phlegm in the back of the throat, and longer mealtimes.

Aspiration, in which foods, liquids or body secretions are routed down the trachea instead of the esophagus, is of particular concern when swallowing problems occur, especially when those difficulties are compounded by a weak cough. Aspiration introduces bacteria to the lungs and may lead to life-threatening infection and pneumonia.

Although aspiration poses serious risks to people with ALS, most tend to focus on excessive saliva as their major complaint, says Laurie Sterling, speech pathologist at the MDA/ALS Clinic at Methodist Neurological Institute in Houston. Drooling can be embarrassing, and it’s scary to cough and choke on your own secretions.

“The concern seems to be about the amount of saliva itself and difficulty ‘breathing through it,’ or coughing on it,” Sterling explains, adding that most aren’t concerned about aspiration or its causes, “perhaps because folks don’t completely grasp the concept of aspiration or realize that you can aspirate your secretions.”

The starting lineup

Several simple and straightforward techniques exist for reducing the risk of aspiration. Sterling suggests:

• tucking your chin down when swallowing to protect your airway;


• thickening liquids to make them easier to control (commercial thickeners, baby cereal, gelatin, cornstarch and instant potato flakes are several options);


• avoiding mixed consistencies (such as chicken noodle soup) that are difficult to manage with tongue weakness;


• taking pills whole with something like pudding rather than water, or crushing them (except for time-release tablets); and


• elevating the head of the bed at least 30 degrees to prevent reflux.

A swallowing evaluation done by a speech pathologist familiar with ALS can identify the specific strategies most helpful for you.

In a two-step laryngeal diversion procedure, the larynx (above the trachea) is cut in two. The upper part is sewn to the esophagus, routing everything from the mouth down to the stomach and eliminating the risk of aspiration. The bottom part is attached to a tracheostomy tube, through which air is routed to the lungs.

Another factor in aspiration risk is oral health. Aspiration of secretions high in bacteria increases the risk of developing pneumonia, so for someone with ALS, keeping the teeth and tongue clean is as important as ever. (Tip: avoid toothpastes, gels or mouthwashes high in sugar or alcohol, as they may encourage production of saliva.)

"I don't think I can stress enough the importance of good oral hygiene, even if you aren’t eating by mouth any longer," Sterling says. "There are a lot of bacteria in the mouth, even more so if oral hygiene is not maintained.”

Covering the bases

Other more complex means of controlling secretions include steam and vibrating vests, in-exsufflator (cough assist) devices and suction machines, and medication.

Steam and vibrating vests both help break up mucus in the lungs, while the latter can be effective in moving secretions from the lungs to the upper airways. The in-exsufflator device helps clear secretions from the respiratory tract by strengthening the force of an individual’s cough through the use of positive pressure on inhalation and negative pressure on exhalation. Suction machines then can be used to suck out any remaining secretions in the mouth or throat.

Anticholinergic drugs such as atropine sulfate (Sal-Tropine), amitriptyline (Elavil) and glycopyrrolate (Robinul) help decrease saliva production, as do scopolamine patches (Transderm Scop), which usually are prescribed for motion sickness and worn on the skin. These drugs block action of the neurotransmitter acetylcholine, responsible (among other things) for transmitting nerve impulses that increase bodily secretions. They produce typically mild side effects such as sore throat (from decreased mucus production), decreased perspiration and less frequent urination, but their effectiveness varies from person to person.

Also effective at reducing salivation are botulinum (Botox) injections to the parotid gland, the largest of the salivary glands. The botulinum toxin works by suppressing the release of acetylcholine. It’s possible to achieve the same outcome by inducing scarring of the glands through ligation (cutting) or irradiation; however, these methods are permanent and tend to be performed much less frequently.

Heavy hitters

A “common and appropriate” treatment to prevent aspiration is insertion of a percutaneous endoscopic gastrostomy tube (PEG, or feeding tube), says Stanley H. Appel, director of the MDA/ALS Center at the Methodist Neurological Institute in Houston. He recommends people with ALS consider getting a gastrostomy early in the progression of the disease to help decrease aspiration risks.

The feeding tube ensures nutrition requirements are met while eliminating aspiration risks associated with chewing, swallowing and eating food. However, feeding tubes don’t prevent aspirating saliva, mucus or stomach contents. When all other options have been exhausted, a surgical procedure may be the method of choice for reducing the risk of aspiration to zero.

In a procedure called a laryngeal diversion, a surgeon cuts the trachea in two. The bottom section is bent and brought out the front of the neck for a tracheostomy; the top section is either sewn off (a “one-step” procedure) or sewn side-on-end onto the esophagus (the “two-step” procedure). With the two-step procedure, anything in the mouth will be routed down the esophagus to the stomach.

“The laryngeal diversion, especially if you do the full [two-step] procedure, completely eliminates the risk for aspiration,” says physical medicine and rehabilitation specialist Greg Carter, co-director of the MDA/ALS Center at the University of Washington at Seattle.

The way in which the procedure is done determines whether or not it is reversible, but it, as all surgeries in people with ALS, poses some risk of exacerbating weakness or causing secondary infections. Also, those who have the procedure done will be unable to communicate via voice or sound, as no air will pass over their vocal chords.

Carter says he rarely recommends laryngeal diversion because he rarely recommends tracheostomy. “Improvements in noninvasive ventilation (NIV) over the past decade or so have been so great that I just find that most people don’t need a tracheostomy,” he says, noting however that tracheostomy is appropriate in cases of severe bulbar involvement, where too much upper airway resistance makes NIV ineffective.

Opinions differ on laryngeal diversion. Appel says the procedure is “too aggressive to handle the problem of aspiration,” and has never recommended it, “because the problem can best be handled by the combination of gastrostomy and noninvasive ventilation.”

Carter, however, suggests anyone with ALS who opts for a tracheostomy get the laryngeal diversion procedure done at the same time. Tracheostomy alone, he says, actually increases the risk of aspiration because the tracheostomy tube promotes secretion production and interferes with the normal swallowing mechanism.

A Grand Slam In February 2003, Steve Nichols of Clifton, Va., had lived with ALS nearly nine years. Both limb and bulbar onset had not only stolen his strength, but severely affected Nichols’ speech and eating habits. “I still tried to talk but anything more than one syllable was unintelligible to everyone, even to my wife’s trained ear,” Nichols says. “I was still eating for taste and pleasure, but the bulk of my diet was given through a feeding tube.” Nichols says his swallowing was “slightly compromised” with a lot of “backwash,” and that without tongue movement to push food around he was unable to chew. He aspirated “moderately,” and “almost without fail on certain pleasure foods, like Reese’s Peanut Butter Cups,” which he was unwilling to give up. He also was having an extremely difficult time coughing up lung secretions, and when he was able to get them up “the volume would be so great it would block my trachea.” He tried an in-exsufflator, steam, and a vibrating vest, in combination with drugs to lessen secretions, Robinul and scopolamine patches, but nothing seemed to help. Two bouts of pneumonia prompted him to search for other solutions. Nichols consulted otolaryngologist (ear, nose and throat expert) Patty Lee at Otolaryngology Associates, P.C., in Fairfax, Va. “Mr. Nichols’ problem was that he was aspirating,” Lee says. “He already had a feeding tube, so it wasn’t that he couldn’t get nutrition, it’s just that he was aspirating on his own saliva.” Nichols opted to eliminate his risk for aspiration altogether with a laryngeal diversion, which Lee performed. “I’m very satisfied with the procedure,” he says. “It was a good move for me.”