Mary Jane Powell, who was not diagnosed until she was 75, and her daughter Doreen Ellis have MS. (Rick Egan/The Salt Lake Tribune)
Thursday, June 8, 2000
BY LEE SIEGEL
THE SALT LAKE TRIBUNE
Doreen Ellis first knew something was wrong while visiting her mother and stepfather during extremely hot weather in Mesa, Ariz., in 1996.
"The whole right side of my face went numb and I couldn't swallow," said Ellis, now 44. "I felt I might be having a stroke."
It was no stroke. The numbness continued for weeks after Ellis returned to her home in Draper. She developed extreme fatigue. Her doctor first sent her to a dentist, who found no sign of pinched facial nerves, and then to a neurologist, who ordered magnetic resonance imaging (MRI) of Ellis' brain.
The scans revealed white spots or lesions on her brain -- a telltale sign of the nerve disorder multiple sclerosis.
Meanwhile, Ellis' mother, former Salt Lake City resident Mary Jane Powell, also was developing strange symptoms.
"I was real tired and weak," said Powell. She had trouble lifting her right leg, making it difficult to climb stairs or to walk in a stable manner.
In 1997, the year after her daughter was diagnosed with MS, a spinal tap and MRI scans revealed that the disease also afflicted Powell, 75 and now living in Idaho Falls, Idaho.
Powell's age made the diagnosis unusual. For most of the 300,000 to 400,000 Americans with MS, symptoms appear when they are 20 to 40 years of age.
But since the case of Ellis and Powell came to his attention, Salt Lake City neurologist John Rose and a Colorado colleague identified six more pairs of young adult to adult children and older parents afflicted with MS.
"Traditionally, the diagnosis [of MS] after age 50 has been looked on very skeptically," said Rose, a University of Utah professor and assistant chief of neurology at the Veterans Affairs Medical Center. "It's been felt those patients have some other disease, some degenerative dementia" such as Alzheimer's disease.
But learning of seven offspring-parent pairs with MS "really raised my awareness there are risks even in older age for multiple sclerosis, and if there's a family history of MS, you'd better look at older individuals in the family carefully when they come in with neurological problems."
The Genetic Factor: The development of MS in adult children and their parents also emphasizes a key question about the mysterious cause or causes of MS: To what extent do genetic factors make people susceptible to the disease, and to what extent is the disease caused by a yet-unidentified environmental factor, particularly exposure to a virus?
MS involves multiple areas of scarring or sclerosis to the myelin coating that insulates nerves of the brain and spinal cord. Symptoms are diverse and can include numbness, weakness and tingling in legs, arms, face and torso; clumsiness; fatigue; disturbances to vision and hearing; memory loss and other intellectual or emotional changes; dizziness; sexual impairment; tremors; trouble with balance; and problems with bowel or bladder control.
While the cause is not known, doctors believe exposure to a virus or some other infection or toxin triggers an autoimmune response in which antibodies attack, inflame and destroy patches of myelin nerve coating.
The disease is twice as common in women as in men, and is more common in temperate climates than in the tropics. That may be due to some seasonal fluctuation in the abundance of viruses, Rose said. The disease has been known since the 1850s, which contradicts occasional claims that nerve gas or some other modern toxic chemical may be involved, he said.
Rose said while genetic factors appear to be involved, environmental factors must play a role. When one identical twin has MS, there is only a 30 percent to 40 percent chance the other twin will have the disease. If MS was purely genetic, both identical twins would always have the disease. About 15 percent of MS patients have a close relative with the ailment. Studies in mice suggest 13 mutant genes may contribute to MS, Rose said.
Most patients suffer the "relapsing and remitting" form of MS in which flare-ups can last for days to months, followed by months or years without symptoms. Flare-ups can occur spontaneously or are triggered by heat, stress or infections.
Some MS patients have the progressive form in which symptoms become increasingly worse in weeks or months, either from the start or after years of relapsing-remitting symptoms. Most MS patients have normal life-spans, although some suffer permanent disability and end up in wheelchairs or die prematurely.
An unusual aspect of the seven offspring-parent pairs studied by Rose and Englewood, Colo., neurologist Ronald S. Murray was that all seven adult children have relapsing-remitting MS, while four of the seven elderly parents had the progressive form of the disease, which makes it harder to diagnose because it can be confused with other progressive diseases such as Alzheimer's or nervous-system tumors, Rose said. Powell was among the three parents with the relapsing-remitting form.
Looking at the Parents: Murray and Rose presented their study of the offspring-parent MS patients last month in San Diego during the American Academy of Neurology's annual meeting. Murray, who trained in Utah, now directs the Rocky Mountain Multiple Sclerosis Center in Englewood, a Denver suburb.
Rose said discovery of offspring-parent pairs of MS patients happened during a long-term genetic study of families with several afflicted relatives. MRI scans revealed the white lesions caused by demyelination in the brains of older relatives, some of whom did not yet have other symptoms.
After that discovery, Rose started seeing older patients with symptoms. He soon learned Murray had seen other older patients. The seven offspring in their study were 16 to 40 years old, while the parents with MS ranged from 43 to 80.
Discovering "late-onset" MS in older adults means studies of the genetics of the disease must carefully look at parents in affected families, Rose said.
He said the existence of offspring-parent MS patients raises the question of whether "the parent and child had some exposure to an environmental agent at a certain time, or is there a genetic phenomenon where offspring manifest the disease earlier in each generation."
Such a pattern is seen in some genetic diseases because mutations grow worse in each subsequent generation, he said.
Rose and U. geneticist Mark Leppert now are trying to identify human genes that contribute to MS by studying 30 families with more than one affected relative.
Meanwhile, Ellis and Powell are coping with MS.
Powell, a retired office worker in the U.s' radiology department, moved with her husband, Gordon, from Mesa to Idaho Falls to escape the heat. She took beta interferon injections for a while, but they failed to reduce myelin inflammation, so she switched to methotrexate, a cancer chemotherapy drug that did reduce the inflammation.
"I'm improving and have more strength, and can tell I'm better," she said. Although she still walks with a cane because her right leg remains weak, "now I can pick up a glass of water with my right hand. I couldn't before."
Her daughter, Ellis, was forced by fatigue to quit her full-time job as medical receptionist and now works part time for a graphic design agency. She had a six-week relapse in late 1999, with numbness on the right side of her face and throat, trouble swallowing and sloppy handwriting.
Ellis was prescribed an antidepressant, which often is used to help
MS patients relax and sleep better, took a steroid to reduce inflammation
during her last flare-up, and now is considering entering a clinical trial
at the U. in which researchers will test the oral form of an injectable
drug that reduces the immune system's attack on myelin.