March 3, 2004
Conceding multiple sclerosis is unruly and unpredictable, researchers nevertheless refuse to see it as untamable.
Taking advantage of the medical and technological breakthroughs of the past decade, investigators have started to crumble the wall of secrecy that has been jealously guarded by the enigmatic disorder since its first description by a French pathologist 136 years ago.
"For the first century, scientists had little more understanding of the disease than that of its existence, and doctors could do little more than try to manage the symptoms," Terence Keane, of the National Multiple Sclerosis Society, noted in a telephone interview. "Now, we are in a period of tremendous progress, with discoveries about the brain and the human genome advancing at a breathtaking pace, (and) it is inevitable that we will find a cure."
Even so, the challenges presented by a disorder as confounding and conniving as MS cannot be underestimated, researchers cautioned.
Multiple sclerosis shreds the fat-cushioned myelin sheath that enfolds nerve fibers in a protective cocoon, cutting critical lines of communication between the brain and spinal cord and the rest of the body. The slowed or severed transmission of electrochemical impulses can lead to failed motor skills and flawed organ function.
The central nervous system disorder also can make mincemeat of disease-fighting mechanisms, leaving the body defenseless against infection-wielding invaders.
Capricious and cruel, MS tends to toy with its hosts, besetting them with wildly ranging mild or severe, enduring or short-lived symptoms, depending on the nerves affected.
In 60 percent of patients, the disease can be stoked by heat, whether generated by the weather, furnace or exercise. In such cases, a cold bath or swim may spell relief, albeit a temporary one.
More than half of those with MS experience muscle weakness in the extremities, difficulty with coordination and balance, an abnormal burning, prickling or tingling sensation in the hands, arms, legs or feet, numbness or feeling of "pins and needles."
About half the MS population has difficulty with concentration, attention, memory, judgment or other cognitive tasks. A smaller portion suffers pain, loss of bladder and bowel control or, in severe cases, paralysis.
For some 20 percent, symptoms stagnate following the initial attack, leaving physical and mental abilities intact. In rare instances, the disease can spiral swiftly toward severe disability or even death -- although, in most cases, MS has no effect on longevity.
The disease can prove lethal if the damage occurs in brain regions that control such vital functions as breathing or blood circulation. In a first-of-its-kind fatality on record, a 14-year-old girl suddenly succumbed 17 hours into a relapse, leading to an unprecedented study of brain tissue from the earliest hours of a bout of the illness. The preliminary results, published Feb. 23 in the Annals of Neurology, imply the disorder may begin with the death of myelin-producing brain cells, theorized study author John Prineas of the University of Sydney in Australia.
The disorder can make a sudden appearance with varying combinations of neurological symptoms, only to vanish sporadically for days, weeks or years in partial or complete remission. Or it can grab an even more merciless hold, progressing unabated toward its destructive destiny.
Between 211,000 and 500,000 Americans suffer from the disabling disorder, with the toll rising by roughly 10,000 new cases each year. The disease takes an estimated $2.5 billion annual bite out of the U.S. economy in healthcare and other costs.
Worldwide, the disorder, which strikes primarily white women and most often is first detected in their 20s and 30s, affects approximately 1.1 million to 2.5 million people.
More precise figures are hard to come by. Physicians are not required to report new cases and because many symptoms are so innocuous, or invisible, they escape detection, Mary Jones of the National Center for Health Statistics in Hyattsville, Md., told United Press International.
Like arthritis or autism, MS is not classified as a "reportable" disease because it is not communicable, infectious, food-borne or resulting from exposure to such potential biological weapons as anthrax, Karen Hunter of the Centers for Disease Control and Prevention in Atlanta, said in a telephone interview.
Most prevalent in northern regions of North America, southern Australia, Italy and northern and central Europe, particularly among those of Scottish stock, the disease is harsher on men but more prevalent among women, by a 2-1 margin. A 2002 study pointed to a 50 percent increase in incidence among women between 1991 and 1994 from the same period in the previous decade.
First described in 1868 by French pathologist Dr. Jean Martin Charcot, who noted numerous scars throughout the central nervous system -- hence its name -- multiple sclerosis was classified in 1996 according to frequency and severity of neurological symptoms, ability to recover and accumulation of damage. The main categories include:
-- Relapsing-remitting: the most common type, affecting some 75 percent to 85 percent of patients, with symptoms that seesaw between peaks of severe flare-ups and valleys of partial or complete recovery;
-- primary-progressive: a form experienced by an estimated 10 percent of the MS population whose condition worsens steadily with little respite;
-- secondary-progressive: relapsing-remitting MS that gradually turns relentless as periods of remission grow fewer and shorter, a fate that had awaited half of patients with relapsing-remitting MS within 10 years of initial diagnosis before the introduction of novel "disease-modifying" drugs in the 1990s, and
-- relapsing-progressive: reported in 5 percent of MS patients, who suffer accumulating damage as the disease waxes and wanes.
The disorder's flightiness has frustrated doctors trying to pin down an early diagnosis to determine the proper course of action. Studies suggest prompt treatment might subdue the severity of the disease and perhaps even slow its progression.
Far from definitive, symptoms -- which can come and go at the disease's whim -- may indicate any number of possible conditions, including Lyme disease, which recent research reveals presents a strikingly similar clinical picture of neurological problems.
Often, the signs of MS have proven so difficult to interpret, physicians have had to resort to a "wait-and-see" prescription. No single laboratory test yet exists to prove or rule out MS, so it may take months or even years to gather the evidence of multiple attacks and nerve damage traditionally thought necessary to make a positive identification.
Researchers, however, are devising ways to hone their diagnostic skills, with the aid of such new technological tools as magnetic resonance imaging, which paints an anatomical picture of lesions, or areas of injury, and magnetic resonance spectroscopy, which portrays the biochemistry of the brain.
Last September, the American Academy of Neurology formally acknowledged the usefulness of MRI, noting the predictive power of even a single image. For example, a patient whose scan shows three or more lesions in the brain's white-matter area has a greater than 80 percent likelihood of developing MS within seven to 10 years.
"Before, the criteria used to diagnose people required neurologists to show that disease activity had occurred in the brain over time," noted study author Dr. Elliot Frohman of the University of Texas Southwestern Medical School in Dallas. "This guideline helps us use MRI to telescope into the future to see what's going to happen with these patients."
Another group plans to glean things to come with a high-tech blood test. Using microarray technology, which enabled them to analyze thousands of genes simultaneously, U.S. and Israeli scientists observed an MS-linked pattern of activation in 1,100 of the units of heredity. Even more suggestive, they discovered a noticeable shift in 200 of them that portended an acute relapse.
The preliminary findings hint the test eventually might help doctors foresee the course of disease in patients without resorting to more invasive procedures, such as spinal taps. It might even help predict a patient's response to therapies, said Dr. Naftali Kaminski of the University of Pittsburgh Medical Center, co-author of the study reported Feb. 2 in the Annals of Neurology.
Dr. Claude Genain, a neurologist at the University of California, San Francisco, hopes one day to make similar forecasts from certain proteins, called antibodies, implicated in MS development.
"Our work is going to change the way we look at patients as we use antibodies as decision-making tools that will help us to determine whether to treat or not to treat, or whether to treat with one approach or another," he told UPI. "This will be practical for the doctor and soothing for the patients who, at least, will be told what the future is probably going to hold and what they need to do to go on with their life."
Already, they have a variety of options.
"In the last 10 years, there has been a tremendous revolution in treatment, with five new medications approved by the Food and Drug Administration, not just for fighting symptoms, but also for stopping the disease in its tracks," Keane noted.
These include the beta-interferons Avonex, Betaseron and Rebif, as well as Copaxone, a synthetic aid designed to facilitate the transmission of nerve impulses. The National Multiple Sclerosis Society has been so impressed with the drugs' effects, it urges their use upon diagnosis of relapsing MS.
"This is the only recommendation of a treatment we have ever made because the data are so strongly supportive of the effectiveness of early intervention in slowing the progress of the disease," Keane explained.
The fifth drug, Novantrone, a chemotherapy agent approved for such use in October 2000, aims to reduce impairment and/or the number of attacks in the more progressive forms of MS. The lifetime dose has a limit to prevent heart damage.
Over the past five years, 50 percent to 80 percent of applicants seeking NIH funding for MS research successfully passed the review process -- compared to fewer than 30 percent of grant seekers overall -- noted Constance Atwell, director of the Division of Extramural Research of the National Institute of Neurological Disorders and Stroke.
"This is a bustling field with a lot of promising new ideas," Atwell proclaimed.
Worldwide, investigators are testing experimental drugs and novel strategies in some 160 clinical trials, and others have projects in the pipeline.
"I am optimistic about our ability to tame the MS beast," Genain declared.
Copyright © 2004, United Press International