Multiple Sclerosis: Who Will Stay Well? Who Will Develop Relapsing MS?

Many people who develop symptoms of multiple sclerosis (MS) aren't diagnosed for several years.

Typically MS causes a cluster of symptoms in one part of the body, and then goes away for several months to several years. Then it reappears as a different cluster of symptoms in another part of the body.

What kinds of symptoms may be the first signs someone has MS?

• It's not unusual for people who are in the very earliest stages of multiple sclerosis to develop paresthesia, a loss of sensation in part of the body.
• About 20 percent of people who have MS develop optic neuritis, loss of vision or color vision in one or both eyes, early in the course of the disease.
• It's also not unusual for people who are in the very earliest stages of the disease to present what appears to be bipolar disorder, except that the psychiatric symptoms almost resolve themselves. Either depression or euphoria unrelated to life events can signal the disease.
• Many people go to the doctor because they have odd twitches in the face, a condition called myokimia, or double vision that comes and goes.
• There can be spinal cord symptoms causing muscles first to become stiff (spastic), followed by painful cramps.

Multiple sclerosis can also manifest itself as dementia (usually only much later in the disease, although sometimes very early on), bladder problems, bowel problems, sexual difficulties, heat intolerance (problems with hot weather or with hot showers or overheated rooms), fainting, dizziness, or weakness of both sides of the face. MS is recognized by the Charcot triad, ataxia (loss of balance), dysarthria (difficulty speaking without difficulties finding words), and tremors. There can be problems with attention span, decision making, and judgment. Pain and fatigue are very common features of the illness.

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Not everyone, however, develops all of these symptoms, and not everyone inexorably gets worse. Multiple sclerosis is typically diagnosed as:

• Relapsing-remitting (RRMS). About 85 percent of people who have MS have this form of the disease when they are diagnosed. All the symptoms go away for a time, and then come back, over a long period of time.
• Clinically isolated MS. These people present symptoms of MS once, and then the symptoms never come back again, even 10 to 20 years later.
• Secondary progressive MS (SPMS). After some years of relapse and remission, the disease reaches a point that symptoms only get worse. Most people who have RRMS eventually develop SPMS.
• Primary progressive MS (PPMS). Diagnosed in about 10 percent of people who have MS at their first presentation of the disease, symptoms only get worse with time. This group has more problems with changes in gait, stiff arms and legs, heavy legs, and inability to walk longer distances.
• Progressive-relapsing MS (PRMS). This form of the disease tends to cause more problems with bladder control, muscle spasms, vision changes, problems with speech, hearing loss, and tremors.

Most people who develop MS symptoms have to wait several years before they know whether they are destined only to get worse or maybe they are among the lucky few who have a form of the disease that doesn't get worse. Fortunately, there's now a test to determine who may be able to look forward to a life free from MS.

Testing to Determine Who Will Develop MS

Why would anyone who has the symptoms of MS want to know for sure they are getting better or worse? If you're one of the few whose symptoms are likely to recover and not suffer progressive disability, of course, you'd like to know. And even if you are an MS patient who is destined for progressive disease, knowing the form of MS you have several years earlier allows you to do more planning, and puts you higher on the list for innovative treatments as they become available.

Immunologist Dr. Nancy Monson, an associate professor in the Department of Neurology and Neurotherapeutics at the University of Texas Southwestern Medical Center in Dallas has developed a test that looks at unique gene mutations in a subset of white blood cells in spinal fluid. Known as B cells, these immune-active cells play a significant role in the development of MS.

MS Is a Condition Caused by an Overactive Immune System

The term multiple sclerosis refers to scars, or sclera, that develop in the brain and central nervous system. More specifically, the lesions that develop in multiple sclerosis occur in the white matter, which conducts electrical impulses between nerves in the gray matter. More specifically, multiple sclerosis involves destruction a subset of white matter cells known as the oligodendrocytes, whose job is making the fatty layers that insulate and protect cells in the white matter.

In MS, one of the things that goes wrong (there are other factors in the disease than just this) is that the immune system produces defective B cells. These B cells normally make antibodies, which are Y-shaped proteins that patrol the body looking for infections. When an antibody encounters the infectious microorganism it is created to destroy, it "sticks" to the germ and destroys it. In MS, something has gone wrong with the production of B cells so that some of them produce antibodies that "stick" to brain cells.

Genetic Testing Reveals Risk of MS

Before the development of this test, the way researchers identified who was likely to develop relapsing-remitting MS and who might have "clinically isolated" symptoms was to perform a very tedious procedure that separated out single antibodies from the thousands of antibodies in a sample of spinal fluid. It simply wasn't practical to perform the procedure in a clinic.

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However, Dr. Monson and her colleagues learned that the "sticky" antibodies associated with MS track to 38 possible mutations in the genes that code the activity of B cells. Instead of looking for a needle in a haystack to find harmful antibodies. Monson has developed an MS PreCISe test that sequences the entire genome to look for the problem genes, with 86 to 92 percent accuracy for predicting who will develop relapsing-remitting multiple sclerosis and who will remain symptom-free.

Implications for Future Treatment

Dr. Monson doesn't suggest that the MS PreCISe test will replace the need for MRI for diagnosing MS. However, she does believe that it will help doctors make the right decisions in treatment. Many of the medications used to treat MS "knock out" the immune system. It may be possible to determine which MS patients don't need them. And in the future it may be possible simply to deactivate the problem B cells without deactivating B cells that fight actual disease conditions.

MS PreCISe may be more generally available in 2017. In the meantime, if you suffer symptoms of MS, ask your doctor about the most appropriate treatment with the fewest side effects on your immune system.