SECOND ALS GENE DISCOVERED

With support from MDA, scientists have found a second gene linked to ALS — a discovery that's expected to improve efforts to understand and treat the disease.

ALS kills muscle-controlling nerve cells (motor neurons) in the spinal cord and brain, eventually leading to paralysis and respiratory failure. Most ALS is sporadic (having no obvious cause), but about 10 percent of cases are familial (hereditary), pointing to genetic defects that can cause the disease.

Indeed, until now, defects in the SOD1 gene on chromosome 21 were the only known cause of ALS. SOD1 gene defects cause roughly 25 percent of the cases of familial ALS, meaning that they account for only about 2 percent of all ALS cases. But this month, two MDA-funded science teams reported that defects in a previously unknown gene on chromosome 2 cause a rare form of ALS called ALS2.

"Knowing so little about what causes ALS has severely hindered the development of effective therapies. These two studies on ALS2 may give us general insights into the disease and how to treat it," said Sharon Hesterlee, director of Research Development for MDA.

The "classic" sporadic form of ALS strikes during adulthood, and is often fatal within three to five years after diagnosis. It destroys so-called "upper" motor neurons in the forebrain and "lower" motor neurons in the brainstem and spinal cord.

ALS2 — also called autosomal recessive juvenile ALS type 3 — manifests around 12 years of age, advances slowly over many years, and takes an especially noticeable toll on the upper motor neurons. It affects a small number of families, mostly in Northern Africa and the Middle East.

Despite those differences, classic ALS and ALS2 share many symptoms and might share a common disease process, according to the scientists who conducted the new studies.

Teppu Siddique

The two scientific teams presented their work in back-to-back articles in the October issue of Nature Genetics. The first team was led by Teepu Siddique, director of the MDA/ALS Center at Northwestern University in Chicago. The second team was led by Joh-E Ikeda of Tokai University in Japan, in collaboration with Michael Hayden of the University of British Columbia and Guy Rouleau of McGill University and Montreal General Hospital in Canada.

Siddique and Rouleau were part of the MDA-funded group that first identified ALS-causing defects in the SOD1 gene in 1993.

"With the discovery of this new gene, we get a more complete view of ALS. It's another piece of the puzzle to how the disease kills motor neurons," he said. Mutations in the gene "could be responsible for some small fraction of seemingly sporadic ALS in North America," he added.

Surprisingly, the studies also implicate the gene in a juvenile form of primary lateral sclerosis (PLS), a disease whose relationship to ALS has been the focus of much scientific debate. Like ALS, PLS destroys the upper motor neurons. But, unlike ALS, it spares the lower motor neurons, leading primarily to spasticity (a loss of fluid movement) rather than paralysis.

"Before, there were two views," said Afif Hentati, a neurogeneticist on Siddique's team. "People either thought PLS was the same disease as ALS or a separate condition. Our results favor the view that PLS and ALS are a single disease entity."

The new gene, which the two research teams have agreed to call ALS2, looks similar to previously identified genes that encode GTPase regulators. These proteins control the activity of GTPases, which use the energy molecule GTP to carry out important reactions within cells. The predicted structure of the ALS2 protein — which Siddique's group has dubbed "alsin" — suggests it belongs to a class of GTPase regulators that control cell shape and integrity, both teams say.

Rouleau and his collaborators found ALS2 mutations in a Tunisian family with ALS2 and in a Kuwaiti family with symptoms closer to PLS. Siddique and his group found ALS2 mutations in an unrelated Tunisian family with ALS2 and in a Saudi family diagnosed with PLS.

The scientists suspect the mutations cause a loss of alsin function, with mild alsin deficiencies causing damage to upper motor neurons (PLS) and more severe alsin deficiencies causing damage to both upper and lower motor neurons (ALS2).

But they have yet to determine exactly why alsin deficiency is detrimental to motor neurons.

"On the surface, [alsin] doesn't have any obvious relation to SOD1, but it's possible they'll somehow fit together," said Rouleau.

Seeking to clarify alsin's role in ALS, the scientists have already identified the mouse version of the ALS2 gene, which can be used in studies of the mutation. Next, they plan to create and study mice that have deletions of the gene.

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HIV LINK COULD LEAD TO ANTI-VIRAL THERAPY FOR ALS

Two new studies show that the AIDS virus, HIV, can cause an ALS-like syndrome that wanes or even disappears upon treatment with anti-HIV drugs.

In one study, researchers at Rothschild Hospital in Paris found that six of 1,700 HIV-positive people developed an ALS syndrome as the first manifestation of AIDS. With anti-viral medication, all improved and two fully recovered from the syndrome.

In the other study, researchers at Beth Israel Medical Center in New York identified a woman who developed signs of ALS, and later tested positive for HIV. After four years of anti-viral treatment, she remained largely free of ALS symptoms.

ALS & HIV

The studies — which appeared in the Sept. 25 issue of Neurology — could lead to routine HIV testing for people with ALS and, in those who test positive, a remarkably improved prognosis. They're also likely to fuel searches for other viruses that cause ALS and to spur clinical trials of anti-viral drugs for ALS.

Burk Jubelt and a colleague

Despite the positive impact of the studies, ALS experts say that HIV probably isn't a major cause of ALS. They point out that the HIV-related ALS syndrome has some distinctions from "classic" ALS, including an earlier age of onset and a more rapid progression. Also, the French study showed that only a small fraction of people who were HIV-positive developed the syndrome.

Still, the French study also showed that the occurrence of ALS in AIDS is more common than ALS in the general population. So it's possible that some instances of sporadic ALS — the 90 percent of ALS cases that aren't caused by genetic factors — might be traced to HIV, and hence effectively treated with anti-HIV medication.

"This isn't going to affect a huge number of ALS patients, but in anyone who is a little unusual or atypical [in age or disease progression], we should look for HIV," said neurologist Burk Jubelt, an MDA clinic co-director at the State University of New York in Syracuse. Jubelt specializes in neurovirology — the study of viruses that attack the nervous system — and wrote an editorial published along with the two studies.

Better Prognosis

Although HIV infection is ultimately fatal, "there are patients with HIV who've been receiving treatment and remained stable for many years," Jubelt added. Usually, ALS is fatal within three to five years of diagnosis.

Researchers aren't certain how HIV might trigger ALS, in which the death of muscle-controlling nerve cells (motor neurons) eventually leads to paralysis and respiratory failure.

"HIV doesn't directly infect neurons," Jubelt said. But in its assault on the immune system, it appears to infect microglia, immune cells that patrol the nervous system for signs of distress. In response, the microglia could try to mount a first-line immune defense, causing inflammation in the brain and spinal cord.

The Virus Connection

Or, by weakening the immune system, "HIV could allow other opportunistic viruses to appear and infect the neurons," Jubelt explained.

In that light, researchers will probably take a closer look at a controversial theory that a family of viruses called enteroviruses can cause ALS. The theory sprang from observations that the best known enterovirus — poliovirus — selectively attacks motor neurons and causes symptoms similar to ALS. But evidence of poliovirus infection in people with ALS has been sparse.

"There could even be viruses that cause ALS that we haven't identified yet," Jubelt commented.

Given that possibility and the fact that the HIV-related ALS syndrome improves so dramatically with treatment, Jubelt said there's a strong rationale for clinical trials of anti-viral drugs in ALS, even in ALS patients who are HIV-negative.

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MANAGING SALIVA IN ALS

A Talk With Neurologist Ashok Verma

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.

  What causes excess saliva and drooling in ALS?
  (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.

  What do you mean by the handling of saliva?
  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.

  How do we normally handle saliva?
  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.

  What happens in ALS?
  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.

Ashok Verma

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].

  How do you treat the excess saliva or drooling?
  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.

  If those medications don't help, what's next?
  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.

  How do you know whether a treatment for sialorrhea is working?
  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.

  Are there other treatments?
  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.

  Do you do anything about the mucus-containing part of the secretions?
  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).]

  How do you usually proceed in treating sialorrhea?
  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.

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HOLIDAY GIFT IDEAS FOR LOVED ONES WITH ALS

Some people say that October is too early to be thinking about holiday shopping. But if you're the kind of Santa who likes to shop around for a while — and if one of the people on your list is affected by ALS — then you'll be smart to get a jump on holiday shopping.

Music, books, artwork, attractive clothing, computer software, aroma therapy diffusers and lava lamps all make great gifts and can be found without much effort. But if you also are looking for a gift that addresses some of the physical limitations of ALS, here are a few suggestions:

The Touch Turner

Reading and Music

Prism Reading Glasses allow users to read or watch television while lying flat on their backs and looking straight up. Designed to be worn alone or over regular glasses. $39.95, Dynamic Living

The Book Butler adjusts to cradle your book at a comfortable reading angle. Pages are turned and held in place using a manual spring post system. $18.95, Independent Living Products

The Touch Turner is a switch-operated book holder and page turner that allows for completely hands-free reading (a variety of switches are sold separately). The forward page-turning model is $800; reversible page-turning model is $980, Touch Turner

Switch-operated cassette player/radio is perfect for music or books on tape. It works with a variety of switches (available separately). $58.36, or $87.95 for a lighted face, Enabling Devices

Hobbies

A stand-alone embroidery hoop holds projects steady and at a comfortable height. $29.99, Dynamic Living

A table clamp with adjustable gooseneck can hold a variety of sewing and other craft projects. $60, Maddak

The adjustable table top, 18-inches-by-22-inches, can be used for painting, reading, studying or crafts. $44.50, MaxiAids Inc.

The Dreamer motorized easel allows an artist to independently reach any area of a canvas by activating a switch: up, down, sideways or tilted. The easel base fits over wheelchairs and twin or hospital beds. $2,800 for the basic unit, Extensions for Independence

Computing

The laptop wheelchair tray is designed to hold both your laptop computer and extra accessories. $90, Maddak

Typing Aid slips on over the hand and has a pencil-sized rubber tip pointer for tapping keys. $17.25, Sammons Preston

Lap Genie

The Lap Genie laptop computer holder allows you to comfortably use your laptop from anywhere and any position, including reclining in bed. Available in four colors, $129, Lap Genie

Personal Comfort

The hand-held infrared heat massager has three interchangeable heads, two speeds and an angled head for easy spot massage. $33.95, MaxiAids

Heated food bowl fills with hot water to maintain food temperature when it takes a long time to finish a meal. $8.99, Maddak

Drink-Aide insulated cup has a long flexible straw and a clamp for mounting on a wheelchair or bedside rail. $36.95, Enabling Devices

CosySoles microwaveable slippers keep cold feet toasty warm. These polar fleece, bootie-style slippers are filled with natural grain that holds heat for about an hour. Pop each slipper in the microwave for a minute, then slip them on and say, "Ahhhhh..." Adult sizes, $39.95, CosySoles

Around the House

Portable door knob turner slips over any regular round knob and converts it to an easy-to-use lever opener. $12.95, Sammons Preston

Multipurpose power grip is a hand-held vise that concentrates limited finger and hand strength for opening, holding, bending and repairing. $19.55, Sammons Preston

Ergonomique pots and pans have specially shaped handles that maximize lifting strength. $52, Easy Street Co.

Easy-access clothing

A battery interrupter allows you to attach a switch to any device that operates on AA, C or D batteries, so it can be operated with little to no hand movement. It's available with a quarter-inch or eighth-inch switch jack. $9.95, Enabling Devices

H-A Modular Mouthsticks enable users with head and neck movement to independently perform a variety of functions, including page turning, painting, typing, dialing phones, writing and drawing. Designed so the user can talk and swallow while using it, the basic mouthstick is telescoping and comes with an integrated pen and an interchangeable eraser tip. Made of lightweight aluminum, the stick has very little flex and accurately transmits mouth and head motions to the tip. It's available in three mouth sizes. $120, Extensions for Independence

Clothing

See "Holiday Gifts That Sparkle With Style," in the October issue of Quest, MDA's national magazine, for ideas on clothing gifts. And watch Quest stories and ads year-round for other gift ideas.

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Medicare Rules Change

Elimination of Waiting Period Increases 'Quality of Life'

A timely copy of The ALS Newsletter saved Adele Avery from taking out a loan to buy a power wheelchair. Instead, she became one of the first people in the country to benefit from a recent change in Medicare rules for people with ALS.

Avery, 61, already was significantly disabled when her condition was finally diagnosed as ALS in January. She had qualified for Social Security Disability Insurance (SSDI) the year before and was almost halfway through the standard two-year waiting period for Medicare benefits when she realized she was going to need a power chair sooner rather than later.

Avery tracked down a used chair about five hours from her Friant, Calif., home, arranged for a loan and had made an appointment to pick the chair up the next day when she happened to see an article in MDA's The ALS Newsletter about the change in federal law.

The new law, passed by Congress in December 2000, exempts SSDI recipients with ALS from the two-year waiting period because of the rapid health decline experienced by many with the disease. As of July 1, everyone with ALS who receives SSDI was immediately eligible for Medicare health coverage benefits.

It Won't Drop Out of the Sky

Avery discovered, however, that being eligible and receiving benefits were two different things. Because she'd qualified for SSDI before receiving an ALS diagnosis, her diagnostic code didn't indicate that she had ALS. Her first step was to get her code changed.

"Through many, many, many, many phone calls, I finally found out that my diagnostic code did not, in fact, reflect that I have ALS," she says. "And once a person's code is in there, it's in there. The computer won't let you just change it."

She also discovered that her local Social Security representatives and the people staffing the Medicare 800 number weren't aware of the change in law. It took the help of a state-funded advocate to get her code changed.

"I did finally get it, but it was a cliffhanger," she says. She urges people with ALS who are waiting for Medicare benefits to check their diagnostic codes. "This isn't just an automatic thing that's going to drop out of the sky. They need to call the local Social Security office and verify that ALS is their diagnostic code," Avery says.

Avery, a former nurse, says obtaining Medicare coverage a full year earlier than expected has been a tremendous asset. The increase in insurance coverage has allowed her to obtain needed durable medical equipment such as a power chair and bedside commode. She also feels fortunate to have received a manual wheelchair and leg braces from MDA.

"It increases your quality of life, because you get the equipment you need while you still have the function — and you have that function for such a short period of time," she explains. "I can still get out and go to church, I can do things that are important to me. I can go to the grocery store with my husband and go out with my neighbor. We just ride around the block and see everybody's flowers. It's wonderful to enjoy the beauty of nature while I still can. Those kinds of things really improve your quality of life."

She adds, "It means that the little bit that you have left is stretched further; you're less dependent, which is psychologically really nice."

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THANKS & CARE ARE KEY FOR HAWAII COUPLE

Hawaii's Bruce Koppel could be forgiven for being what his wife, Jessie, labeled "the most serious person — a boring professor."

After all, Koppel, 58, has enjoyed a career that has taken him around the world and given him the opportunity to study, teach and live among a variety of foreign cultures.

Jessie and Bruce Koppel at a 1999 conference in Manila where he presented a paper via a talking computer program.

Koppel, who has a doctorate in rural sociology from Cornell University, has worked for the University of Hawaii's East-West Center since 1973. There, he's led many research projects and ultimately served as the center's vice president for research and education.

His successful career has also included publishing several books and reports, involvement in professional organizations, and stints as a graduate student in Asia and as a visiting professor in Paris and the Philippines.

But an odd thing happened when Koppel was found to have ALS in 1997: The serious professor became not-so-serious.

"Now he is just so happy-go-lucky, and never gets depressed," Jessie Koppel said. "Since he has had ALS, he's always smiling. He's stress-free and he's even a flirt."

The remarkable transformation may be due to the fact that Koppel knew what to expect from the disease, which also claimed his mother and her sister. He was prepared both financially and emotionally for what might come.

More likely, Jessie said, it's because he's shed the demands of a prestigious academic career. Bruce says he now lets others do the worrying for him.

All-Inclusive Care

Koppel receives round-the-clock care from Jessie and a team of seven nurses. His routine includes both conventional medicine and alternative therapies. Jessie's caregiving involves not only taking care of Bruce's medical needs, but also creating a positive, stimulating environment for him.

"Bruce cannot go out every day, so I have the world come to him," she said.

Friends and colleagues stop by the couple's Honolulu home every day and read books, play music or talk about current events with her husband. Koppel is still involved in some of the research at the East-West Center, and stays in touch by e-mail or through such visits. A Web site at www.koppel.org celebrates highlights of his career.

Koppel can no longer speak and sometimes communicates with the help of a computer, but he often gets across what he needs to with his eyes, Jessie said.

Jessie's regimen for her husband also includes monthly massages, facials, chiropractic care and Reiki, a method of natural healing based on the application of energy. She laughs about how her husband has actually gained weight despite the progression of ALS, and he has received compliments on how healthy he looks.

"I am very proud of my husband, and I am very proud of how I take care of him," she said.

The couple met in the Philippines when Koppel was a graduate student, and he hired her to be his research assistant. Later, she jokes, "he fired me as a research assistant, but gave me a job as his wife." The two married in 1971, and have a son, Eli, now an attorney in New York.

Koppel communicates with other people affected by ALS via e-mail and Internet chats, and the couple is also very involved many aspects of MDA. Jessie Koppel is an executive committee member of MDA's Hawaii Chapter, and is the chairwoman for the Rainbow of Hope ALS Dinner in November, at which her husband will be the honoree. She also is a real estate agent.

While her schedule can be arduous, Jessie said, she feels taking care of her husband is a natural role.

In the first few months following his diagnosis, she said, "I was tired because I was learning about the disease. You have to learn to work less and more effectively."

Learning from Experience

Jessie Koppel now has many caregiving aspects down to a science, and freely shares her innovative tips with other families affected by ALS. See "Tips From the Koppels."

For instance, it's possible to have just about any supplies you need delivered to your home for no extra charge or a very small fee.

"The only thing I go out for is to the drugstore to pick up his meds. Everything is ordered and delivered on a regular basis," she said.

Other tips she's learned from experience: Appreciate the people behind the scenes at doctors' offices and hospitals.

Following a doctor visit or a hospital stay, Jessie always sends a token of appreciation, such as a basket of fruit or some Filipino food, to the medical professionals who treat her husband. She's sure to include the entire staff, especially nurses and receptionists, on a thank-you card. The simple gesture helps the staff remember the Koppels when times of medical need arise.

"I find that it works for me. When I call, I'm always connected right to the doctor. Even if he's doing a procedure, he always gets back to me," she said.

All the experience and the care and planning are further bolstered by the Koppel family's strength and attitude in the face of ALS.

"Every morning when I get up I thank God that he's still alive, and I think that's what I project to him," Jessie said. "We just accept it and live to the fullest."

In a recent interview with a Hawaii newspaper, Bruce Koppel said his advice to others beginning a battle with ALS is: "Don't look back, and appreciate each day."

Tips from the Koppels

Here are some caregiving tips and hints that Jessie Koppel has found helpful to her family in dealing with Bruce's ALS.

STRESS AND ALS

What You Need to Know — And What to Watch For

There's no gauge by which to measure the overall stress level of a nation. But if there were, it would certainly show that our collective stress level increased dramatically on Sept. 11.

When terrorists struck the World Trade Center and the Pentagon, they not only attacked America — they attacked each and every one of us individually. And each of us is experiencing some degree of stress in the aftermath.

Stress and ALS

When you experience stress, your body responds in the same way as it does when you're in danger. It produces stress hormones such as adrenaline and cortisol to help you deal with the immediate threat. Those hormones tell your body to give all its attention to the threat, diverting it from many normal operations — including the immune system's job of protecting you from bacteria, viruses and other unhealthy "invaders." This can be a dangerous omission for people with neuromuscular disorders such as ALS.

Since people with ALS often have weakened breathing muscles, they're often more susceptible to respiratory problems — particularly pneumonia, which can be life-threatening. Reacting to stress can leave you vulnerable to respiratory infections and other health threats.

The immune system can be damaged by stress in another way. It communicates closely with the nervous system in ways scientists don't yet fully understand. But studies have repeatedly shown that having negative thoughts and emotions in our brains, such as worry, fear, anger or depression, makes the immune system less effective.

As those who've outlived the "three-to-five-years" prognosis in ALS often say, a positive, upbeat attitude can be extremely helpful, while a pessimistic, defeatist attitude can be deadly.

Paul J. Rosch, M.D., president of the American Institute of Stress, cautions that there are no hard and fast rules that can be applied to the subject of stress.

"It's unique to each individual," Dr. Rosch says. "What causes distress in one person can actually be pleasurable to another. While there's no question that stress can directly impact health, there are no 'one-size-fits-all' strategies for dealing with stress."

Jan Stolee, a mental health counselor who facilitates MDA support groups in the Seattle area, says the link between stress and the progression of ALS is well known.

"I don't have any idea what it would have to do — medically speaking — with the course of ALS as such," she explains. "But any disease course works better if people are not stressed. The body simply functions better."

And the effects can often reach beyond the patient, affecting caregivers and family members, as well.

"When you have an ALS patient, the whole family is very profoundly affected," Stolee says. "Having to deal with getting on with their lives, or coping, or just dealing with all of the new disabilities — it seems like there's a new one every week."

Why Now? Why This?

Since Sept. 11, Americans have experienced a range of emotions from unimaginable horror in response to images on TV, to an almost inconsolable sense of grief at the loss of so many of our fellow countrymen. We also may be feeling intense anger toward those who've attacked our country.

Rosch suggests that one aspect of these stressful emotions is a feeling of powerlessness. None of us could have prevented this awful tragedy, none of us can do anything to make the victims' families whole again, and we're uncertain how to prevent a recurrence.

"Powerlessness is a terrible feeling," Rosch says.

Stolee agrees. "You didn't do anything wrong to 'deserve that' or to make it happen," she says. "Therefore, you can't do anything to make it never happen again, or to undo it."

Stolee says this kind of stress "very much mimics neuromuscular diseases. You get a diagnosis and there's nothing you can do. It's terrible, and I don't know how people cope with that — but somehow they do."

Stolee points out that dealing with ALS is stressful enough in itself. The resulting vulnerability can often lead to a lesser capacity for dealing with additional stress.

"It's like another big load on top of what you're already trying to deal with," she says.

"Each person is different," she explains. "In a sense, the better the functioning or coping mechanisms somebody has, or maybe the more mental health they have, the better they will do. People who are prone to depression anyway, or have had difficult life circumstances, may be already worn down a bit and this is just another added burden. And people can really only tolerate so much."

Is It Safe?

In the 1976 film "Marathon Man," Dustin Hoffman portrays an American college student taken prisoner by a fugitive Nazi, portrayed by Laurence Olivier. During an interrogation scene, Olivier's character repeatedly asks Hoffman, "Is it safe?"

Hoffman's character, having no idea what the question means, tries every answer he can think of. But none of his replies seem to satisfy his captor.

In a sense, that's the question that Americans are having so much trouble answering today. Are our lives safe? If having a neuromuscular disease makes you vulnerable, can you possibly be safe in a world in which terrorists can attack American cities?

Stolee explains it this way:

"There's danger all around us — from cars, crossing the street, riding a bike. But we have a way of kidding ourselves, or walking around in denial, so to speak, which is actually quite functional. We really believe we're safer than we actually are. But there's just so much of the world that we don't have control of, and I think that something like this episode reminds us of that."

It can alleviate some of our stress to realize that, while our feelings of safety and security have been shaken badly, we're no more — and no less — safe and secure today than we were before Sept. 11.

Stress Can Be Depressing

Both Rosch and Stolee say the greatest health risk associated with stress lies in its potential to lead to depression.

According to the National Depressive and Manic-Depressive Association (http://www.DBSAlliance.org), there are several signs to watch for, if you're concerned that you or a loved one may be experiencing clinical depression — the kind that lasts for more than a few weeks:

1. Prolonged sadness or unexplained crying spells
2. Significant changes in appetite or sleep patterns
3. Irritability, anger, worry, agitation, anxiety
4. Pessimism, indifference
5. Loss of energy, persistent lethargy
6. Feelings of guilt, worthlessness
7. Inability to concentrate, indecisiveness
8. Inability to enjoy former interests, social withdrawal
9. Unexplained aches, pains
10. Recurring thoughts of death, suicide

A pretty broad list of behaviors, to be sure. The key lies in knowing yourself or your loved one, talking through these issues as much as possible, and watching closely for any signs of unusual or abnormal behavior. If two or more of these symptoms persist beyond a couple of weeks, you should take steps to pull yourself out of the slump. If some of the following suggestions don't help, get professional assistance from a clergy member, counselor or physician.

What Can We Do?

If feelings of powerlessness are at the root of the stress, Stolee says, the best way to fight back is to take some form of action.

"Write a letter to your congressman, or a letter to the editor of your local newspaper. It doesn't matter whether you get an answer back or not," she says. "The point is that you were able to do something."

It may also make you feel a little more powerful to fly the American flag or support survivors and relief efforts.

Your friends at MDA have another suggestion.

Three days after the World Trade Center bombing, MDA National Chairman Jerry Lewis wrote a letter to the editor of U.S. newspapers, urging support of the International Association of Fire Fighters' New York Fire Fighters 9-11 Disaster Relief Fund. In his letter, Lewis says: "Our emergency forces have given their all for us, time and again. Now it's time for us to provide them with help and hope."

Be Good to Yourself and Your Loved Ones

Here are some other things that may help.

1. Hug somebody, anybody. Talk to them about how you're feeling, and ask them to do the same. Then hug them again.
2. As much as possible, keep up your normal routine. Take your medications on schedule and go to your normal appointments — clinic, physical therapy, etc.
3. Go to the next MDA support group meeting, even if you've never gone before. Maybe the other people there can help you, or maybe you can help them.
4. Do something fun. Anything that will take your mind off the stress — however briefly — will help.
5. And most of all, take care of yourself — physically and emotionally.

The essence of depression is feeling that you're alone, trying to deal with a dangerous, complex world.

That's why you hear President Bush and other leaders express the importance of unity. That's why we're so deeply touched by images of people from other countries mourning our loss.

So remember: Being a member of the MDA community means the same thing today as it has for 50-plus years: You don't have to face this alone.

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NEW ENGLAND ARTIST LIVES ALONG THE SCENIC ROUTE

"So when the day comes to settle down, who's to blame if you're not around? You took the long way home..."

  Supertramp, 1979

Fred Siwak not only stops and smells the roses along the way: He looks for ways to capture their beauty in his artwork.

From Coast-to-Coast... and Back Again

Siwak, 49, graduated from the University of Connecticut in 1974, then worked as an employment specialist until he moved to San Francisco. After working in a variety of jobs, Siwak became a paralegal for 10 years.

Then, the story took a twist that most folks with ALS will find familiar.

"It's a bit like nightfall," he explains. "The sun is getting gradually dimmer, but you don't really notice it until it's dark."

In 1997, Siwak began to experience difficulty using his right hand. He also noticed that he didn't have as much energy as he did before. Then, he started to limp when he walked, and found himself falling frequently.

"One time I fell in the middle of the street," he recalls. "Everyone thought I was drunk, and no one helped me."

In the spring of 1998, he received a diagnosis of ALS. "Once you're diagnosed, then you start looking back and you can see the signs," he says.

Siwak was fitted with ankle-foot orthoses to help him walk, and he began to attend ALS support group meetings. He soon concluded that his days of independent living were numbered and decided to move back to his native New England, where his family lived.

Taking the Long Way Home

"This disease is pretty overwhelming," Siwak says. "You don't think you're ever going to get something like this. I was always physically active. I exercised, I walked all over San Francisco, I hiked, I was always outdoors."

Siwak packed his sleeping bag, some clothes and a cooler in a van and set out. "It took me all morning just to load those few things into the van — something that would've taken most people a few minutes."

Fred Siwak

The drive itself took longer, as well — but this had less to do with Siwak's ALS than with the route he chose.

"I drove over 6,000 miles," he says. "It was my last chance to see the West."

"Each day, I rested and reserved enough strength to do things like pump gas and turn the key in the ignition."

First, he drove to Nevada, then to the Grand Teton Mountains and Yellowstone National Park in Wyoming. From there, he traveled through Montana to Alberta, Canada, and back down through Oregon to California, before finally pointing his van toward the East Coast.

From Explorer to Artist

"That's Fred's style — what makes him unique," says recently retired MDA Health Care Services Coordinator Marcia Randall. "He sees life as a journey, and he's determined to capture everything he can along the way."

And while ALS has slowed down the activities of Fred Siwak the explorer, it's given him more time to develop Fred Siwak the artist. "Before ALS, I just dabbled," he says.

Siwak carves images into linoleum tiles, which he then uses to create prints. After the prints dry, he colors them in with pastels, making each print unique.

"It takes months to carve each block," he says. "Because I'm adamant about doing everything myself."

Siwak's art has won rave reviews, earning first prize at the Topsfield, Mass., Fair in both 1999 and 2000. In December, he joined prominent Massachusetts artists Tina Carrick and Linda Siwak (Fred's sister-in-law) to present the Light and Vision exhibit at the Topsfield Library.

Attitude and Daily Life

These days Siwak uses a power wheelchair to do his exploring by day, and regulates his breathing with a BiPap machine at night. He can no longer grip with his hands, so he's adapted a universal cuff eating strap with a special pocket that holds his carving chisel in place.

He's learned that the keys to daily life with ALS are controlling stress and conserving energy.

"I just found that I get peace of mind breaking things down to day-to-day problems," he explains. "I get irritated when I don't have things set up the way they need to be, and that's when I have to remind myself to take things easier."

Perhaps the most difficult challenge for the fiercely independent Siwak has been relying on others for help.

"A lot of people give support in small ways, and MDA — in particular — has been great," he says. "I just like the tone of how they don't forget about me, and I get swift treatment without a lot of forms."

ALS may ultimately win its battle with Fred Siwak, but don't be surprised if it takes extra innings to do so ... he's always likely to take the long way home.

For more information about prints of Siwak's artwork, e-mail him at seaweed@gis.net.

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'I'LL ALWAYS BE GRATEFUL' TO MDA

Dear Jerry,

For the longest time, I always thought that you and my dad were very similar in nature ... both with beautiful eyes, a great sense of humor, religious and extremely committed when you believe strongly in something. Each year I would watch you on the MDA Telethon, and it would be like I was spending time with my own dad, who was usually busy at work, or in some other city during his retirement years as a sports memorabilia collector and salesman.

Who would have guessed that I would soon connect you two on a more personal note? I always wondered if all the stories on the Telethon were true ... maybe too good to be true. And then, my dad became one of the many who were diagnosed with ALS.

I found out really fast that what I saw on the Telethon is what he got in the way of treatment and service and love! It was as if each MDA person who interfaced with Dad and the family were like guardian angels put right here on Earth to come to the rescue.

We all thought that Dad had been having symptoms of ministrokes because his speech was slurred and he was having difficulty swallowing. After about a year, he suspected, and was diagnosed with, a sporadic version of the bulbar variety of ALS, which strikes the throat and chest area first.

Stanley Appel, who I suspect is the ALS research equivalent to our famous cardiovascular surgeon, Michael DeBakey [both are at Baylor College of Medicine and both are MDA national vice presidents], advised Dad that he probably had 12 to 18 months to live. My dad suspected that he didn't even have that long. Since Dad was already over 70 years old, this bulbar variety of ALS was known to be rapid in its progression.

So like anyone who has a fighter spirit, my Dad kept trying to be as viable as he could, for as long as he could. He got a g-tube, and regained some weight, and some strength and mobility. But his balance was getting bad, and he had to wear a neck brace. He couldn't drive, eat, talk or drink anymore.

He was a couple of days away from his regular appointment with Dr. Appel, where he planned to ask for the prescription for a wheelchair or walker. Out of the blue, while walking back home, he fell back and fatally injured his brain. We'll never know if he had a stroke or a heart attack or what, but it was fast. And he was spared the advanced symptoms of ALS that would have eventually stolen his life.

I kept hoping that stem cell therapy could have been a possibility for him, and I hope this method will be perfected in time to save so many others who are falling victim to this and many other debilitating conditions.

Why am I writing you? Well, to thank you for your commitment, and to thank you for bringing this tragic illness to the forefront. And because it's good to know that there is an entire network of folks who can help make the necessary resources available to lend quality to what's left of one's dignity until there's a cure. And because I feel even closer to you and your organization now in your effort to bring this "dis-ease" to "ease" when a cure is within our reach.

Thank you and your organization for all the difference you have made in our lives and so many others' lives. It really is like what I saw on all the Telethons all these years. I'll always be grateful.

Susan Grossman
Houston

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ALS AUTOBIOGRAPHY

In the Garden of Gethsemane, by Joan Schuster with James A. Costa Jr., 196 pages, 2001, $12 plus $3 for mailing. Order from Jim Costa, 6 Hidden Valley, Elma, NY 14059, (716) 652-6755.

Joan Schuster is 51 years old and has lived with ALS for 30 years. In this poignant autobiography, Schuster writes of youthful dreams realized only to be lost with the diagnosis of ALS at 21. She frankly expresses the full range of emotions with which she struggled as her disease progressed quickly in the early years — feelings of fear, helplessness, anger, loneliness and depression.

She's also refreshingly candid about the way these feelings conflicted with her strong Christian faith, her belief and trust in a divine plan for her life.

Ten years into the disease she faced the decision to enter a nursing home. Again, she wrestled with a range of emotions, and here she describes her day-to-day challenges, successes and disappointments. Again, her faith carried her through.

Without being preachy, this is an honest, often raw, story of courage; a story about how to live, not how to die, with ALS; a story of a woman who doesn't regret what's lost but fully appreciates what's left.

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FALL ONLINE CONFERENCE SERIES BEGINS

MDA President Robert Ross knows you have questions about ALS, and he knows where to find the most accurate answers to those questions — at one of MDA's 25 ALS research and clinical centers.

For those who don't live near an MDA/ALS center, Ross has decided to bring center directors to you — via a four-week conference series at MDA's Web site, www.mda.org/chat/calendar.html.

Walter G. Bradley, medical director of the Kessenich Family MDA/ALS center at the University of Miami, will open the ALS Fall Conference Series on Oct. 24, from 10 to 11:30 a.m. (All times given are Eastern.) Bradley will discuss the status of ALS research and treatments.

On Oct. 31, at the same time, Bradley and other members of the center's staff will be available to answer questions online, this time covering everyday living.

The series continues in November, with the virtual spotlight on Jeremy M. Shefner, medical director of the MDA/ALS Center at SUNY Health Sciences Center in Syracuse, N.Y. Shefner will discuss ALS research on Nov. 6 from 12 to 1:30 p.m. On Nov. 13, he'll address respiratory issues from 12 to 1 p.m.

These conferences are open to anyone, at no cost. All you need to do is register with MDAchat. Once you've registered, simply log onto MDAchat at any time during the conferences and you're in. You can either ask questions of the conference leaders, or you can simply follow along.

Did Somebody Say 'Chat?'

The newest ALS chat made its debut on Aug. 27. "Living With ALS" is held every Monday at 2 p.m. Hosted by Jeff "ragingbear," this chat is for people with ALS and their caregivers.

The "ALS Chat Group from Connecticut" holds a monthly chat from 2:30 to 4:30 p.m. on the third Tuesday of every month. This chat is open to anyone who wishes to discuss any aspect of either ALS or MDA.

And don't forget David Jayne's monthly "Issues That Matter" chat, held every fourth Tuesday from 9 to 10 p.m.

What If I Can't Make It?

If you've missed a chat session or online conference, simply click on the "transcripts" button at the top of the MDAchat page at www.mda.org/chat/calendar.html. There you'll find transcripts for past chat sessions and online conferences.

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Flu Shots

Once again MDA is offering free flu shots for those affected by ALS and other neuromuscular disorders.

Influenza is especially dangerous to people with muscle-wasting diseases, which can compromise the muscles used in breathing.

People registered with MDA can get their flu shots from their local MDA clinics, or MDA will pay for a local doctor to administer the shot.

HELP FIGHT ALS TODAY AND TOMORROW

Many people who know the devastating effects of ALS are providing lasting support for MDA's battle against the disease. Through your will, you can designate a gift to MDA earmarked to support ALS research or services.

To give what remains of your estate after other bequests have been satisfied, just include the following language in your will:

"I give, devise and bequeath all (or a specified fraction of) the rest, residue and remainder of my estate, whether real or personal, of every kind and description, and wherever situated, to Muscular Dystrophy Association Inc., a New York not-for-profit corporation having its principal office at 3300 East Sunrise Drive, Tucson, Arizona, 85718-3208, for its program of research and services related to amyotrophic lateral sclerosis."

To give a dollar amount or percentage of your estate:

"I give, devise and bequeath the sum of $________ (or ________ percent of my estate) to Muscular Dystrophy Association Inc., a New York not-for-profit corporation having its principal office at 3300 East Sunrise Drive, Tucson, Arizona, 85718-3208, for its program of research and services related to amyotrophic lateral sclerosis."

Your attorney or financial adviser can help you work out the details of a bequest to MDA's ALS Division. For more information, call MDA's Planned Giving Department at (800) 572-1717.

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