Multiple Sclerosis: The State of the Art

Posted By SHL Librarian

Presented by Lucas B. Kipp, MD, FRCPC
Clinical Assistant Professor, Neurology & Neurological Science
March 8, 2018

Multiple sclerosis no longer has to be an inevitable slide into a crippled state. For people getting diagnosed and treated early, newer drugs have dramatically reduced the risk of declining into disability.

But challenges remain for people who didn’t get help soon enough to preserve their abilities. No drugs are available yet to roll back the disability they’ve already developed. Researchers are pursuing solutions with urgency.

“The need is there. We know it,” said Lucas Kipp, MD, FRCPC, in a lecture on multiple sclerosis at the Stanford Health Library.

Multiple sclerosis is a challenging condition. The first symptoms can be sporadic attacks of tingling, numbness, or weakness on one side of the body. Some people lose vision in one eye.

Over years, that can give way to weakened muscle coordination, stiffness and spasms, making it difficult to walk. There can be problems with speech or swallowing.

Why attacks happen

Multiple sclerosis is considered an autoimmune disease. That means the body’s immune system mistakenly reacts to its own tissues as though they are foreign, and attacks them.

In general, autoimmune diseases attack different parts of the body. In rheumatoid arthritis, for example, the immune system attacks the joints. In multiple sclerosis, the immune system attacks myelin—the protective covering around nerves in the central nervous system.

Without this protective covering, nerves misfire and the communication between the brain and the rest of the body suffers.

What triggers an attack

It’s still a mystery what triggers the mistaken immune system attack, said Dr. Kipp, who is an assistant clinical professor of neurology and neurological science. Some evidence suggests that certain viruses may resemble myelin. If someone is infected with one of these viruses, over time the immune system may mistake myelin for the virus and try to defend the body by attacking myelin.

If the nerve communication suffers, that’s when people start noticing symptoms. The symptoms typically build up over hours to days and then persist for a while before fading away, but often leaving residual deficits. These attacks are called “flares” or “flare-ups.”

What increases risk

Doctors understand even less about why some people develop multiple sclerosis, and others don’t, Dr. Kipp said. Although there may be a genetic or hereditary influence, environmental factors are probably responsible for 75 percent of the probability that someone will get the disease.

Environmental factors include:

  • Exposure to certain viruses including the Epstein Barr virus, which causes mononucleosis. “That’s not the whole story,” Dr. Kipp said. Most people infected with that virus don’t get multiple sclerosis.
  • Where you live. The farther away someone lives from the equator, the higher their risk of multiple sclerosis. That’s because people get less sunlight in northern (and southern) areas of the globe.

Sunlight is converted to vitamin D in your skin. Vitamin D is actually a hormone that affects many body functions including the immune system.

Lack of vitamin D is “probably the risk factor we know the most about in multiple sclerosis,” Dr. Kipp said.

  • Obesity.  The risk of developing multiple sclerosis is higher in those overweight, especially women. Some evidence suggests that fat cells hold onto vitamin D, making it harder for the vitamin to circulate in the bloodstream. That may prevent vitamin D from maintaining health throughout the body.
  • Smoking.
  • Composition of the microbiome in your gut. The microbiome contains many kinds of bacteria. If the microbiome has an imbalance of more “bad” (pro-inflammatory) bacteria than “good” (anti-inflammatory) bacteria, that may tip the immune system towards an autoimmune reaction.

Balancing act

That has led some people with multiple sclerosis to wonder if they should take probiotics or similar supplements to help keep their gut microbiome balanced.

“This is what everybody’s question is,” Dr. Kipp said, referring to his patients. But he said it’s too early in the studies of the gut microbiome and multiple sclerosis to know the answer yet.

“You go to Walgreen’s or CVS, and there’s a whole wall full of probiotics,” Dr. Kipp said. “Which one should I take for my MS?”

“I can’t answer that yet, because we’re not sure how to rebalance it.”

Studies are being proposed to research this and similar questions. One small study of a probiotic called propionate, which is a byproduct of some gut bacteria, had encouraging results, Dr. Kipp said.

The study found MS patients taking this probiotic for 3 months had more anti-inflammatory cells and fewer pro-inflammatory cells in their blood. Nobody knows yet, however, whether these changes will lead to slowing or stopping of multiple sclerosis attacks.

Getting a diagnosis

When people begin to notice symptoms like numbness or tingling that suggest multiple sclerosis, getting a diagnosis is often a challenge. Early symptoms of multiple sclerosis symptoms can be difficult to interpret because they are so variable and unpredictable.

Symptoms may come and go over a long period of time. So far, there is no single test to diagnose the disease. Doctors rely on a thorough clinical history, neurologic exam, blood work, MRI and sometimes spinal fluid to make the diagnosis.

Medical guidelines for making a diagnosis call for evidence on 2 levels:

  • Evidence of 2 separate episodes of an inflammatory attack on the central nervous system over time
  • Evidence that each attack occurred in different places in the central nervous system.

The evidence can come from:

  • A detailed medical history finding clear symptoms that follow the typical time course for multiple sclerosis

For example, you wake up one morning and go to work and notice one hand is numb and tingling. By the end of the day, the numbness and tingling have spread all the way up your arm. By the next day, the whole side of your body feels that way. Then, gradually over weeks to months, it improves.

  • A neurologic exam pointing to lingering evidence of previous attacks in your central nervous system.

Sometimes you are left weaker on one side of the body than the other.  In some cases, a doctor examines the back of your eye and sees residual damage to the optic nerve corresponding to vision you may have lost during a prior attack.

More tests

Even if the evidence seems convincing, there are additional ways to support a diagnosis of multiple sclerosis:

  • MRI (magnetic resonance imaging) scans show “white spots” or “lesions” in the brain in characteristic locations (around the ventricles).  However, not all white spots on an MRI scan are cause by multiple sclerosis.  Other causes include high blood pressure or migraine headaches.  So an MRI scan isn’t enough to make a diagnosis unless you have also had the physical symptoms typical of an MS attack.
  • A spinal fluid test showing the presence of oligoclonal bands (proteins that suggest inflammation). With this test, some patients can get a diagnosis after experiencing symptoms of only a single attack (backed by a clear and convincing MRI scan), rather than having to wait to see if they get a second attack or new spots on an MRI.  For many patients this allows the diagnosis to be made earlier and treatment started at the very first sign of the disease.

“We’re trying to diagnose you earlier, so we can get you on treatment earlier,” Dr. Kipp said “The earlier you get on treatment, the better we think you’ll do 20, 30, or 40 years down the road.”

Accuracy crucial

Still, doctors must take care to get clear and convincing evidence of the diagnosis. Other common conditions—including high blood pressure, high cholesterol or migraines –can cause a similar looking MRI scan.

“If we get the diagnosis wrong, we’re committing you to a lifetime of immune therapy, and we’re not ultimately treating the real underlying condition,” Dr. Kipp said.

If a well-intentioned doctor makes an inaccurate diagnosis, treatment can sometimes do more harm than good. For example, another autoimmune disease called neuromyelitis optica can resemble multiple sclerosis in symptoms, but treating this condition with multiple sclerosis medications can make this other condition worse.

Faster and better

Almost 2 decades of medical progress in detecting multiple sclerosis is finally helping patients get accurate and earlier diagnoses, Dr. Kipp said. The median length of time taken to get a diagnosis fell by more than two-thirds from 2000 to 2010, from 2 years to about 6 months.

Newer techniques for MRI scans can sometimes detect white spots in very early stages of multiple sclerosis, even before symptoms appear or are noticed. Likewise, better tests have been developed to rule out conditions that mimic multiple sclerosis such as neuromyelitis optica, for which there is now a blood test.

“The earlier we can find these things, the earlier we can intervene,” Dr. Kipp said.

Without treatment, people with multiple sclerosis are much more likely to develop permanent disability down the road. The natural history of most untreated individuals with the disease follows a common course:

  • The first stage, which can last years, called “relapsing-remitting” multiple sclerosis. During this time, people get temporary, intermittent and distinct attacks of neurologic symptoms ranging from numbness, tingling, weakness, bowel or bladder problems, incoordination, vertigo, vision loss, etc.  While most recover to a certain degree, there are usually lingering symptoms and disability that accumulates with each attack.
  • By 10-15 years, many patients transition into secondary progressive multiple sclerosis. The big attacks may subside, but symptoms they have accumulated from those early attacks begin to worsen slowly year by year.  This stage is highly resistant to treatment, so early intervention is important to keep this stage of disease at bay.

Prognosis improved

The risk of facing this daunting decline has improved dramatically for people getting an early diagnosis of multiple sclerosis in recent years. There are now 15 different medicines available for people in the remitting-relapsing stage of the disease. Many are helped before they decline to the second progressive stage.

In the 1980s and early 1990s, before these drugs were available, 80-90 percent of people with multiple sclerosis were using a walker, cane or crutch by the time they reached age 65, Dr. Kipp said. With the development of stronger MS therapies in the last 10 years, combined with earlier diagnosis and treatment, the number is estimated to drop to only 20 percent.

“If we diagnose you now, in 2018, at the very first sign of the disease, I tell people in the clinic that their lives shouldn’t be any different than what they had planned,” Dr. Kipp said. “That’s amazing to be able to say.”

He added, however, that many of the newer drugs have more serious but rare potential side effects and that even our best medications don’t work for everyone. “There’s no guarantee that something that works in the person beside you is going to work for you,” he said. Yet with 15 different drug options, the chances are good that most patients diagnosed early can get a medicine that helps them.

Last frontier

The last frontier is finding a treatment for people who have already advanced to chronic disability. While research funding for this goal has expanded, progress so far is modest.

One newly FDA approved drug shows evidence it may help slow the progression of disability in people with primary progressive multiple sclerosis.  This form of multiple sclerosis presents with a slow increase in symptoms from the beginning without the typical “attacks” seen in the more common relapsing-remitting disease.

There are still no FDA approved medications for secondary progressive multiple sclerosis, but a number show promise in clinical trials.

But the bigger goal is to improve physical abilities, rather than merely slow the decline. In one small study of 154 people, two-thirds were given a high dose of biotin (vitamin B7), and 12 percent showed either an improvement in their disability or walking ability. Researchers are trying to confirm these results in a larger study.

“Wouldn’t it be great if we could reverse that?” said Dr. Kipp said.

Restoring myelin

To achieve a reversal of symptoms and disability, researchers may have to find a way to restore the damaged myelin that covers nerves and repair the underlying nerves themselves, which can also be damaged over time. Studies are underway, but answers may be years away.

Stem cell therapies are also being studied but are in very early stages. “My word of caution about stem cell therapies is that there aren’t any that are currently FDA-approved,” he said.

Dr. Kipp advised people not to try stem cell treatments unless they are a part of a university-sponsored research project.

He was optimistic that research will produce benefits for people who already have entered the second, advanced stage of the disease.

“There is hope that we’re going to have remyelinating therapies in the future,” he said.

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Lucas B. Kipp, MD

Stanford Multiple Sclerosis Center