Technology aids MS detection, but diagnosis still challenging

The use of MRIs to map the condition of the central nervous system has been helpful in identifying the illness.

By Susan J. Landers, AMNews staff. July 14, 2008.

Washington -- Multiple sclerosis is beginning to reveal some of its secrets to the researchers who study the disease that plays havoc with the central nervous systems of about 400,000 Americans.

Although its cause remains elusive, a possible scenario for its development includes a genetic predisposition that may be influenced by infectious agents and environmental factors, said researchers at a June 24 Capitol Hill briefing.

The event was sponsored by the Society for Women's Health Research and the National Multiple Sclerosis Society.

About 20% of people with MS have a family history of the disease, said Henry McFarland, MD, chief of neuroimmunology at the National Institute of Neurological Disorders and Stroke.

Studies comparing identical twins and fraternal twins have offered evidence of the disease's genetic component. According to researchers from the University of California, San Francisco, the risk for developing MS when one twin has the disease is 2% for an unaffected fraternal twin and between 25% and 30% for an identical twin. But findings also point to a strong environmental influence because only a minority of genetically identical twins are both affected with MS.

The disease is generally more common among people of Northern European descent, and some populations have a very low incidence. For example, although MS is rare among Hungarian Gypsies, it is relatively common among other Hungarians, Dr. McFarland said.

Research indicates that a complex interaction of genes, perhaps between 50 and 100, is at work in the development of MS, Dr. McFarland said. A consortium of researchers in the U.S. and the United Kingdom have joined together to try to unravel the genetic influences, he noted. Last year two more genes were identified.
A diagnostic advance

Until recently, the disease has been difficult to diagnose, since its symptoms, which are many and varied, are shared with other conditions. But this ambiguity also can be a diagnostic clue: "The more difficulty people have in trying to explain the symptoms, the greater the likelihood that it is MS," said Heidi Crayton, MD, medical director of the MS Center of Greater Washington and an assistant professor of neurology at Georgetown University Medical Center in Washington, D.C.

Muscle rigidity is probably among the most widely recognized, but other systems can include bladder and bowel problems, numbness and tingling, pain and vision problems. "For years people with MS have been told there is no pain involved, but that's just not true," she added.

20% of people with multiple sclerosis have a family history of the disease.

Among the most troubling symptoms is the cognitive difficulty that comes from loss of brain tissue in some patients, Dr. Crayton said. "This symptom is common, especially in untreated patients."

The 45% to 65% of patients who will develop cognitive impairments within 10 years is a "huge issue now," she said. It also is the focus of treatment.

Detection of the disease has become easier with the use of MRIs, which can make the "invisible visible," she said. Brain atrophy and spinal cord lesions are clearly seen in scans. But the link between MRI findings and the clinical status of a patient is not clear, she noted.

A number of possible triggering infectious agents have been studied, including the herpes virus and the Epstein-Barr virus, Dr. Crayton said. "We're starting to see that many people who have MS have also had mono infections in the past."

In addition, advances have been made in understanding the environmental factors involved in the disease, Dr. McFarland said. Ongoing studies are looking at exposure to ultraviolet light and the relationship of vitamin D levels before MS onset.

A "hygiene hypothesis" also is being investigated, he said. The thought behind this notion is that people with good hygiene are more vulnerable to the disease.


ADDITIONAL INFORMATION:
The 4 courses of MS

People with multiple sclerosis typically experience one of four disease courses, each of which might be mild, moderate or severe.

Relapsing-remitting: Marked by clearly defined attacks of worsening neurologic function -- also termed relapses, flare-ups or exacerbations -- that are followed by partial or complete periods of recovery. During this time, no disease progression occurs. Approximately 85% of initial diagnoses involve this form of the disease.

Primary-progressive: Characterized by slowly worsening neurologic function from the beginning with no distinct relapses. The rate of progression may vary, with occasional plateaus and temporary minor improvements. About 10% of diagnoses are this form.

Secondary-progressive: After an initial period of relapsing-remitting MS, this course is marked by a steadily worsening condition, with or without occasional flare-ups, minor recoveries or plateaus. Before disease-modifying medications became available, about 50% of relapsing-remitting MS cases evolved into this form within 10 years. Long-term data are not yet available to determine if treatment has delayed this transition.

Progressive-relapsing: This relatively rare (about 5%of cases) course is marked by a steadily worsening disease from the beginning, with clear attacks of worsening neurologic function. The disease continues to progress without remissions.

Source: National Multiple Sclerosis Society


Facts on MS

* Approximately 400,000 people in the United States currently have multiple sclerosis.
* An estimated 200 additional people are diagnosed with the disease each week.
* Worldwide, MS affects more than 2.5 million people.
* Researchers have identified factors in the distribution of MS cases that eventually may help pinpoint the causes of the disease.
* These factors include gender, genetics, age, geography and ethnic background.

Source: National Multiple Sclerosis Society

Cancer Drug Rituxan Cuts MS Flare-ups

Studies Show Multiple Sclerosis Patients Taking Rituxan Have Fewer Brain Lesions
By Charlene Laino

WebMD Medical News
Reviewed by Louise Chang, MD

May 1, 2007 (Boston) -- A drug that is already used to treat cancer and rheumatoid arthritis cut by more than half the chance that people with multiple sclerosis would have their symptoms flare up over a six-month period, researchers report.

In two early studies, people taking the drug, Rituxan, also had fewer areas of damage, or lesions, in their brain than those on placebo.

"We believe that if we can prevent these lesions, we can modify the course of this disease," says researcher Stephen Hauser, MD, chairman of neurology at the University of California, San Francisco, and president of the American Neurological Association.

If the research pans out, "this would be a very attractive and probably blockbuster therapy," he tells WebMD.

The research was presented at the American Academy of Neurology's 59th Annual Meeting.



How Rituxan Works
The exact cause of multiple sclerosis (MS) is unknown. But the disease is thought to be triggered by a malfunction in the immune system that prompts immune cells to attack the brain and/or spinal cord. The most common form of multiple sclerosis is a relapsing-remitting form in which relapses or "attacks" of worsening neurologic function appear, and then disappear, for months or years at a time.

Like many other drugs for MS, Rituxan targets the immune system to help calm the inflammation that scars nerves, leading to disease progression. But Rituxan homes in on the immune system in a brand new way, Hauser says.

The drug works by targeting cells in the immune system called B cells, which make antibodies that contribute to the disease process. B cells also secrete chemicals that can encourage inflammation, he says.

Though never compared head-to-head, the early research hints that the drug is twice as effective as drugs such as interferon that are now used to treat multiple sclerosis, he says.

Also, it's more convenient, requiring only two infusions every six months or so instead of the daily to weekly injections associated with current therapies, Hauser says.

Fewer Flare-ups in People on Rituxan
Both of the new studies involved people with the relapsing-remitting form of MS. In the first study, 69 people were given two one-hour infusions of Rituxan two weeks apart and 35 were given a placebo.

Over the next six months, 58% fewer people taking the drug had their symptoms flare up than those taking placebo: 14.5% of those on Rituxan experienced at least one relapse compared with 34.3% of those receiving a placebo.

Also, those on Rituxan had 91% fewer brain lesions seen on MRIs than those on placebo, Hauser says.

The second study, designed to look at the safety of the drug, showed "no unexpected problems," says researcher Amit Bar-Or, MD, of the Montreal Neurological Institute at McGill University in Montreal.

Twenty-six of 28 people were able to complete the 48-week study, in which they received two infusions of Rituxan two weeks apart and then another course six months later.

Most side effects were limited to mild to moderate reactions to the drug infusion, such as headaches and chills, Bar-Or tells WebMD. The two people who dropped out had infusion-related headaches.

Both studies were supported by Genentech Inc., and Biogen Idec., the companies that market the drug for certain types of lymphoma and for a moderate to severe form of rheumatoid arthritis in the U.S.

Safety a Concern
Gary Birnbaum, MD, director of the Multiple Sclerosis Treatment and Research Center in Golden Valley, Minn., says a big worry is a rare but rapidly fatal viral infection known as progressive multifocal leukoencephalopathy, or PML.

And while people on Rituxan appear to have fewer MS flare-ups, "we still don't know if it will actually stop disease progression," Birnbaum tells WebMD.

"These are important observations," Birnbaum says. "But we need longer trials to assess safety and effectiveness."

Immediate Drug Therapy Better Than Waiting
In a third study presented at the meeting, researchers reported that people who immediately start taking Betaseronat the first signs of MS are 41% less likely to have another attack over the next three years than those who delay treatment until they are diagnosed, as is currently done.

Betaseron is a brand of the interferon beta medications that are already used to treat people with relapsing-remitting MS. Other brands of interferon beta, which may reduce the frequency of relapses and delay disability, are Avonex and Rebif.

"I was one of those skeptics who told patients [who had one attack] we could wait," says researcher Mark S. Freedman, MD, director of the Multiple Sclerosis Unit at the University of Ottawa.

"But it turns out there is an 80% chance a person who has one attack will meet the criteria for MS by two years," he tells WebMD. "Immediate treatment can prevent or delay the chance of progression."

Freedman says it's possible that immediate treatment with the other interferon beta medications would provide the same benefit. "But it hasn't been shown."

SOURCES: American Academy of Neurology 59th Annual Meeting, Boston, April 29-May 5, 2007. Stephen Hauser, MD, chairman of neurology, University of California, San Francisco; president, American Neurological Association. Gary Birnbaum, MD, director, Multiple Sclerosis Treatment and Research Center, Golden Valley, Minn. Amit Bar-Or, MD, Montreal Neurological Institute, McGill University, Montreal. Mark S. Freedman, MD, director, Multiple Sclerosis Unit, University of Ottawa.

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