ADVANCES IN INCLUSION-BODY MYOSITIS

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Confusion and Frustration

Rabi Tawil is studying the inflammatory aspects of inclusion-body myositis.

Neuromuscular disease specialist Richard Barohn at the University of Kansas calls IBM a frustrating disease for patients. Barohn, who has been an MDA research grantee and an MDA clinic director at the University of Texas in Dallas and San Antonio, will coordinate the Kansas City part of the interferon trial.

"Most folks have gone many years before getting diagnosed," he says. "The average length of time in our study was eight years. Most doctors don't know how to recognize IBM."

He tells people that "it's not ALS and they're not going to die from the disease. We tell them they're going to experience some disability problems, some weakness in their quadriceps muscles and in their finger and hand muscles. We have them see specialists in physical therapy, occupational therapy, all the rehabilitation specialists, and we try to help them adapt to their disabilities. Once people have some knowledge of the disease from doctors and from MDA, it goes a long way in letting them deal with it."

IBM looks like ALS in that it affects middle-aged and older people and often affects the swallowing muscles early. It looks like polymyositis in that both are inflammatory muscle diseases that involve weakness of the arms and legs. But, says Rabi Tawil, an experienced clinician doesn't have too much trouble telling the difference — even before seeing a biopsy sample.

Higgins and his niece, Sierra Radloff Bill Higgins Mission Viejo, Calif. Bill Higgins, 43, tended to put his increasing muscle weakness out of his mind as much as he could until a fall at age 36 at the gun shop where he was working sounded a wake-up call. Catching his jacket on the edge of a file cabinet ended in a broken arm and a dislocated shoulder, and eventually led him to the office of neurologist King Engel at the University of Southern California and a diagnosis of IBM. After extensive tests and a trial of prednisone failed to help, Higgins says he became "de-pressed, shocked, angry and scared," uncertain of how far the disease would progress. In fact, his increasing disability cost him his job and his apartment. After moving in with his parents, he spent a lot of time immersed in video games at a nearby arcade and tried fishing and model building. A new focus came when he discovered skydiving. Amazingly, Higgins found he was able to participate in parachute jumping, despite leg weakness that keeps him using a wheelchair "99 percent of the time" and hands too weak to lift a cup to his mouth. The sport has helped his frame of mind, as has being part of a core of regulars at an MDA support group. "People in the support group are genuine," he says, "and that's something I wasn't used to. You can sit there, talk, have fun, and it's no big deal. Everyone there has had ups and downs. Most of the time, it's pretty much up."

While PM affects females more often than males and doesn't particularly target older adults, IBM affects males more often than females and usually strikes after 50. In PM, the weakness is mostly in the proximal muscles, those closest to the center of the body, such as the hip and shoulder muscles, while in IBM, weakness of the distal (far from the center) muscles is at least as great.

"When you've seen IBM patients, you can pick them out even before you see the biopsy," Tawil says. "They have distal weakness, finger flexion weakness, and selective weakness of the quadriceps muscle. They sometimes also have swallowing problems. Often, people with suspected polymyositis are treated with corticosteroids, and often they don't get better. Two or three years later, they have another biopsy and their 'steroid-resistant polymyositis' turns out to be inclusion-body myositis."

Therapies and Devices

Treatment for IBM is, unfortunately, not very effective, and the verdict on exercise isn't in yet. Barohn encourages people to walk or swim while they can, but he doesn't try to force an exercise program.

"Usually, when people with IBM lose the ability to walk with a cane or walker, they go to a motorized scooter," Barohn says, noting that a wheelchair isn't always needed. He sometimes recommends bracing some of the finger muscles, but he hasn't found leg braces to be very useful in IBM. Swallowing problems can be overcome with the help of a speech therapist.

Engel takes a similar approach, perhaps being a little more likely to try prednisone. "We've had some patients who are distinctly improved on it, in a sustained way, and a number of patients who are not," he says. Engel has also found that intravenous immunoglobulins help some people with IBM if they're given in adequate amounts and often enough.

Engel encourages IBM patients to use a walker when leg weakness and lack of grip strength make canes unsafe for support. He's seen too many falls with broken bones, including a fatal skull fracture in one person with IBM, he says.

When it comes to exercise, Engel advises people to take an "intuitive approach," noting that the subject really hasn't been studied. "If you're exhausted by the exercise, don't do that much the next time," Engel says. "Mild exercise is appropriate. If the muscle feels sore afterwards, then it's too much." Swallowing muscles can sometimes be aided by prednisone, he says, as well as by dilation of the esophagus by a specialist.

Aging Population, Aging Muscles

"In the 21st century, people are going to live to be older, to 85 or 90 as a normal phenomenon," Askanas says. "We have an aging cell in this disease, but we know very little about aging muscle in general. We need to learn more. We're going to see a lot of diseases associated with aging. IBM is one, but there are more."

Engel examines Harry Farrell, who has inclusion-body myositis.

Research in IBM will benefit research in other disorders of aging, Askanas believes, just as research in those disorders may help IBM researchers make pro-gress. For the present, Askanas and many others are trying to leave no stone unturned. She and several colleagues recently published a paper that suggests yet another lead: The mitochondria — cellular powerhouses that produce energy — in IBM muscle samples frequently contain an abnormality that may be of some importance, although it isn't yet clear where this finding fits into the whole picture.

Finding the genes that cause hereditary IBM will open new doors to all forms of the disease, Askanas notes, just as finding a genetic mutation that can cause ALS has had implications for the nongenetic forms of that disorder. Askanas is confident that the chromosome 9 form of the disease will be demystified soon. The gene, she says, is being searched for and will "pop out" any day now.