by Diana Price
Although a seasoned hospice nurse, Brenda Burroughs never liked going to the doctor’s office herself. So, even though she’d lived for years with vague indications that something was wrong with her nervous system, she found it easy to explain her concerns away. “The symptoms I had were very vague—I could just chalk them up to Oh, I’m just really tired or I’m just a clumsy person—I don’t walk straight,” she remembers.
But about eight years ago, when she was 49, things changed. Right before Thanksgiving, her right thumb and index finger went numb. Then it was the next finger, then all of her fingers. The next day her whole hand was numb, then her arm, and then her shoulder. Then her toes went numb. All this was accompanied by fatigue like she’d never felt before. When she couldn’t lift her Thanksgiving turkey into the oven, she finally called a neurologist.
A magnetic resonance imaging (MRI) scan of her brain showed the hallmark scarring of multiple sclerosis, often known by its abbreviation, MS. MS is an autoimmune disorder, where the body’s immune system mistakes some of its own cells for a threat such as a virus and attacks them.
In MS one of the main mistaken targets is myelin, the protective coating of the body’s nerve cells, found throughout the brain and spinal cord. Mary Rensel, MD, a neuroimmunologist at the Cleveland Clinic’s Mellen Center for Multiple Sclerosis Treatment and Research, likens myelin to the insulation around a lamp cord. If the insulation gets damaged, the electrical signal can’t travel from the socket to the lamp and the light won’t turn on. Similarly, if the immune system chews through the myelin on a group of nerve cells, those nerve cells can’t transmit the information they receive, and some part of the body will malfunction.
Multiple Sclerosis (MS) is a disease of the central nervous system, or CNS (the brain, optic nerves, and spinal cord). Its course is unpredictable and severity can range from mild to disabling. MS disrupts communication between the brain and other parts of the body. As a result, people with MS may experience vision changes, muscle weakness, and difficulty with balance and coordination, along with many other symptoms.
MS is often considered an autoimmune disease, or a disorder where instead of attacking foreign substances such as germs, the body’s immune system attacks its own healthy tissues. In people with MS, the immune system attacks the myelin, which insulates and protects the nerves of the CNS.
MS affects both men and women but is significantly more common in women—almost twice as many women as men have MS. It’s estimated that approximately 400,000 people in the United States have MS. MS is most often diagnosed in people between the ages of 20 and 50 but can also appear in children, teenagers, and older adults.
Types of MS
There are four different types, or courses, of MS. Each can be mild, moderate, or severe.
Relapsing-remitting MS - This is the most common form of MS, affecting approximately 85 percent of people diagnosed with the disease. Relapsing-remitting MS is characterized by attacks (also called relapses, flares, or exacerbations) that are followed periods of complete or partial recovery (remissions).
Primary-progressive MS - This type of MS affects approximately 10 percent of those diagnosed with MS. Unlike relapsing-remitting MS, there are no distinct relapses or remissions. Primary-progressive MS is instead marked by progression, which may vary in severity. People may experience occasional plateaus in progression as well as temporary minor improvements.
Secondary-progressive MS - Many people who initially have relapsing-remitting MS develop secondary-progressive MS. This type of MS involves disease that steadily worsens. There may or may not be occasional flare-ups, remissions, or plateaus.
Progressive-relapsing MS - This is a relatively rare type of MS, making up 5 percent of cases. It’s characterized by a steady worsening of the disease along with attacks of worsening symptoms. Some people do experience periods of recovery, but there are no remissions, and the disease continues to progress.
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Causes of MS
The cause of MS is not known, but researchers have identified several potential factors in its development. It’s generally believed that MS is an autoimmune disease, meaning that it is the result of abnormal activity in the immune system, where the myelin is attacked. As well, environmental factors may be involved—MS occurs more frequently in regions farther from the equator, suggesting a geographic link; and because people in these regions receive less sun exposure and therefore may have lower levels of vitamin D than people in sunnier regions, researchers are questioning the role of Vitamin D deficiency in the development of MS. There may also be genetic factors that make some people more susceptible than others. And, although MS occurs in most ethnic groups, it’s more common in Whites of northern European ancestry than in other groups. It’s also thought that certain viruses or infections may trigger MS.
More is understood about what causes the symptoms of MS than about causes of the disease itself. Symptoms of MS are the result of an immune system attack on the myelin. These attacks damage and scar the myelin in multiple places within the CNS and permanently sever some underlying nerve fibers. The scars are referred to as sclerotictissue. As a result, the CNS can’t effectively send nerve signals to other parts of the body. This altered communication between the CNS and the rest of body causes the symptoms of MS.
Symptoms and Diagnosis
No one experiences MS in the same way. Symptoms vary for each person. Symptoms are also unpredictable—some may come and go, and others may remain constant.
Most Common Symptoms:
- Problems with walking, balance, and coordination
- Bladder dysfunction
- Bowel dysfunction
- Vision problems
- Dizziness and vertigo
- Sexual dysfunction
- Cognitive dysfunction
- Emotional changes
Less Common Symptoms:
- Speech disorders
- Swallowing problems
- Hearing loss
- Breathing problems
Consistent with the mysterious nature of MS, there is yet no definitive test to diagnose or rule out the disease. Diagnosis is further complicated by the fact that symptoms of MS are similar to several other disorders. Doctors take several steps to make a diagnosis: a medical history, a neurologic exam, and various tests including magnetic resonance imaging (MRI), visual evoked potentials (VEP), and cerebrospinal fluid analysis. As well, several criteria are applied to make a diagnosis of MS; these include evidence of damage in at least two separate areas of the CNS, evidence that that damage occurred at least one month apart, and the ruling out of other possible diagnoses.
How the tools for diagnosis work:
- MRI: By taking an image of different parts of the CNS, MRI is used to look for damage to the CNS (called MS plaques, scarring, or lesions). MRI alone can’t be used to diagnose MS because there are other conditions that can cause lesions in the CNS.
- VEP: These tests record the nervous system’s response to visual stimulation. When the myelin has been damaged, response time is slowed. While VEP is considered the most useful evoked potential (EP) test for detecting MS, EPs can also measure auditory and general sensory response.
- Cerebrospinal fluid analysis: A spinal tap is used to take a sample of cerebrospinal fluid, which is evaluated for the presence of certain immune system proteins as well indicators of an immune response called oliogoclonal bands. These bands are present in the spinal fluid of about 90 to 95 percent of people with MS.
Research into a cure for MS is ongoing, but there is no cure yet. Treatment is instead focused on symptom management, on slowing the course of MS, and on maintaining quality of life and ability to function. Because MS is different for each patient, treatment plans with vary and will also be determined by the type of MS a patient has.
Medication - Drugs approved by the FDA to treat MS are intended to reduce the severity and frequency of MS attacks, reduce the areas of damage (lesions) in the brain, and may slow the progression of disability.
The following drugs are examples of agents that may reduce disease activity and progression in people with relapsing forms of MS and people with secondary-progressive disease who have relapses:
- Avonex® (interferon beta-1a)
- Copaxone® (glatiramer acetate)
- Extavia® (interferon beta-1b)
- Navantrone® (mitoxantrone)
- Ponvory (ponesimod)
- Aubagio (terifluomide)
Ponvory™ (ponesimod) is the most recent approved medication for the treatment of adults with relapsing forms of multiple sclerosis, including clinically isolated syndrome, relapsing-remitting disease and active secondary progressive disease.
Ponesimod is a once-daily oral selective sphingosine-1-phosphate receptor 1 (S1P1) modulator that was FDA approved based on results from a clinical trial directly comparing ponesimod to Aubagio (terifluomide). Results showed that the annualized relapse rate was reduced by 30.5% for Ponvory compared to Aubagio. Side effects were similar. (15,16)
In addition to controlling symptoms and disease progression, treatment of MS also involves managing flares (exacerbations or attacks). Flares may be mild and short-lived, or they may be severe and persist for weeks or months. Severe flares are most commonly treated with high-dose corticosteroids, which reduce inflammation.
Other drugs are often prescribed to help manage symptoms of MS. Symptoms for which medication may be prescribed include spasticity, pain, bladder problems, fatigue, sexual dysfunction, weakness, and cognitive problems.
Other Approaches to Managing Symptoms
In addition to medication, symptoms of MS can be managed with lifestyle choices, or self-care techniques (for example, moderate exercise when appropriate, adequate rest, nutrition, and avoiding excessive heat), with rehabilitation (with a physical or occupational therapist, speech pathologist, cognitive rehabilitation specialist, and others), and with the use of assistive devices such as canes, foot braces, walkers, and wheelchairs. These interventions are intended to help people with MS maintain the ability to function—at home and at work.
Living with MS What to Expect
While it’s true that MS can be disabling, it’s important to know that most people with MS do not become severely disabled, and for most life expectancy is normal or near-normal. Many people continue to walk, though some eventually need help doing so, such as a cane or crutches. If weakness, fatigue, or balance makes walking difficult, some people find using a scooter or wheelchair helpful.
Many people with MS benefit from emotional support, as the disease, its progression, and unpredictable nature can present evolving emotional challenges and ups and downs. Caregivers of people with MS can also benefit from such support. Mental health professionals (including psychiatrists, psychologists, social workers, and counselors) as well as support groups can help people with MS and their caregivers develop coping, communication, and stress management skills and address emotional changes like mood swings and depression.
An Individual Disorder
Because the nerves in the brain and nervous system that are damaged by MS can vary widely among patients,1 the disorder’s symptoms are also highly individual. “If you meet 100 patients with MS, you’ll see 100 different forms of MS,” Dr. Rensel says. Some of the more common symptoms include the fatigue, numbness, tingling, weakness, and balance problems that Brenda experienced, as well as blurred vision or vision loss, difficulty concentrating, and bladder or bowel issues.
Women are about three times as likely as men to be diagnosed with MS.2 The disorder tends to strike relatively early in life, with most patients first experiencing symptoms between the ages of 20 and 40.3 When Brenda finally received the diagnosis in her late forties, the neurologist told her, based on the damage shown on her MRI, that “I had actually had it for 15 to 20 years before I was diagnosed,” she says.
What causes MS—what drives the immune system to attack myelin—remains unclear. The disorder has a genetic component— people with family members who have MS are more likely to develop it themselves—but there is no single “MS gene.”3 The environmental factors most strongly associated with developing MS are smoking and previous exposure to a virus called Epstein-Barr (EBV), the virus that causes *mononucleosis.*4
But few smokers develop MS, and about 90 percent of adults have been exposed to EBV sometime in their life,5 yet fewer than 150 in 100,000 people in North America4 develop MS every year. EBV does not directly cause MS, explains Dr. Rensel, “and you can’t catch MS from someone.”
Most patients with MS—about 85 percent—have the relapsing-remitting form of the condition;6 that is, symptoms flare up as new damage occurs but then die down again for months or even years. Over time this often develops into secondary progressive MS, where symptoms continuously worsen over time. About 15 percent of patients have primary progressive MS, where the symptom-free periods of relapsing-remitting MS are never experienced.
Though MS is estimated to shorten a person’s life expectancy by only five to 10 years, its impact is great in terms of disability, loss of employment and productivity, and medical costs.7
Modifying the Course of Disease
Some good news for people diagnosed with MS is that the past few decades have seen a revolution in therapies for the disorder. Before 1993 not a single drug was available that could alter the course of MS.7 There is still no cure, but today 13 so-called disease-modifying therapies are on the market8—drugs that target the misfiring immune system and that, when given early to patients with relapsing-remitting MS, can potentially reduce the number of relapses and slow the march toward progression (see sidebar “FDA-Approved Therapies for Relapsing-Remitting MS”8). Several drugs approved since 2010 come in pill form7 instead of the daily self-injections required with older medications.
Sometimes patients—especially those with mild MS who largely feel fine day to day—are reluctant to start a disease-modifying therapy right away, says Dr. Rensel: “Some people want to try diet or lifestyle [changes] or stress management, which are also superimportant with multiple sclerosis, but I would say, Why not use all the tools in the tool box? because the chance that multiple sclerosis may lead to some kind of neurological disability is high.” Early treatment has been shown to be associated with a reduction in the progression of disability for patients with relapsing-remitting MS.9
It is important, she adds, to balance the risk of relapse and progression for each patient with the potential side effects of the medications. The newer, more potent drugs have higher risks of side effects, including damage to the liver and white blood cells, which require consistent monitoring,7 but they may have particular benefit for people with MS at high risk of frequent relapse.
Keeping a patient’s MS under control while managing side effects may require changing medications more than once. “We tell patients that…the decision we make today [about medication] isn’t a decision for their whole life,” says Dr. Rensel. Brenda is currently talking with her doctor about trying her third medication since diagnosis. The first one worked for a while but eventually stopped suppressing the MS, and the other eventually caused her white blood cell count to drop too low.
A factor for some women with MS to consider when talking with their doctors about disease-modifying therapies is pregnancy. Because MS is often diagnosed in a woman’s child-bearing years, “a lot of times it’s on people’s minds very early in the course of the disease,” says Dr. Rensel. Though women with MS do not have any specific trouble with conception, pregnancy, and delivery, one of the newer drugs has the potential to cause birth defects, and the safety of several others is unclear, making careful planning around pregnancy vital.
In addition to disease-modifying therapies, other treatments exist—both drugs and nondrug interventions—that help patients manage MS symptoms. “This is important because often people have the expectation that a [disease-modifying therapy] is going to make them feel or function better, and they become discouraged and stop treatment when it doesn’t,” says Barbara Giesser, MD, a neurologist at the University of California, Los Angeles, who specializes in multiple sclerosis.
An aspect of MS treatment that has undergone a huge recent shift is how doctors view the role of exercise for MS patients.10 “Back in the bad old days, people with MS were told, ‘Don’t exercise; take it easy.’ If you could have picked the one single worst thing we could have told them, that would probably have been it,” says Dr. Giesser.
Fortunately, “the pendulum has swung completely in the opposite direction for a couple of reasons,” she says, with doctors now strongly advocating physical activity for MS patients. One reason is that not exercising puts people at risk for other health problems, some of which, like high blood pressure, are in turn associated with worsening MS—a vicious circle.
Another reason is that “exercise has been shown to improve certain symptoms of MS, including fatigue, depression, and spasticity,” says Dr. Giesser. “And I think what’s most exciting is that we’re starting to get some information that exercise may actually improve cognitive performance in people with MS, as well. Problems with memory, thinking, and cognitive processing can affect about 50 percent of people with MS, and right now we don’t really have good pharmacologic treatments for that,” she adds.
People with MS can overheat easily during exercise, and this overheating can temporarily exacerbate MS symptoms, although permanent damage is not being done.11 Dr. Giesser tells her patients to do things like exercise under a fan, drink cold liquids, and use cold cloths: “employ cooling strategies— but exercise.”
Physical rehabilitation, such as physical therapy, occupational therapy, cognitive therapy, and speech therapy, is also “super important” for patients with MS, says Dr. Rensel. Several rehabilitation interventions have been shown to decrease disability and improve participation in daily activities and quality of life for patients with MS.12
Much work by MS researchers remains to be done, as drugs that work to slow or stop progressive MS are desperately needed. Researchers are also looking for ways to coax the body to repair damaged myelin, using stem cells or so-called re-myelenation therapies, which ramp up the body’s natural healing mechanisms.
For now Brenda encourages newly diagnosed patients to find the most experienced doctors they possibly can. “When you’re newly diagnosed, you don’t know what [questions] to ask,” Brenda says. She recommends finding a neurologist who specializes in MS: “that all they do is treat MS patients. It’s worth a drive to have someone who knows MS inside and out and can better focus on what’s going to work for you.”
FDA-Approved Therapies for Relapsing-Remitting MS
- Wagner CA, Goverman JM. Novel insights and therapeutics in multiple sclerosis. F1000Research. 2015;4(F1000 Faculty Rev):517. doi: 10.12688/f1000research.6378.1.
- Dunn SE, Lee H, Pavri FR, Zhang MA. Sex-based differences in multiple sclerosis (part I): Biology of disease incidence. Current Topics in Behavioral Neurosciences. 2015;26:29-56. doi: 10.1007/7854_2015_371.
- Hemmer B, Kerschensteiner M, Korn T. Role of the innate and adaptive immune responses in the course of multiple sclerosis. Lancet Neurology. 2015;14(4):406-19. doi: 10.1016/ S1474-4422(14)70305-9.
- Belbasis L, Bellou V, Evangelou E, Ioannidis JP, Tzoulaki I. Environmental risk factors and multiple sclerosis: An umbrella review of systematic reviews and meta-analyses. The Lancet Neurology. 2015;14(3):263-73. doi: 10.1016/S1474-4422(14)70267-4.
- McKay KA, Tremlett H. The systematic search for risk factors in multiple sclerosis. The Lancet Neurology. 2015;14(3):237-8. doi: 10.1016/ S1474-4422(15)70015-3.
- McKay KA, Kwan V, Duggan T, Tremlett H. Risk factors associated with the onset of relapsing-remitting and primary progressive multiple sclerosis: A systematic review. BioMed Research International. 2015;2015:817238. doi: 10.1155/2015/817238.
- English C, Aloi JJ. New FDA-approved disease-modifying therapies for multiple sclerosis. Clinical Therapeutics. 2015;37(4):691- 715. doi: 10.1016/j.clinthera.2015.03.001.
- The Importance of Long-Term Treatment for Multiple Sclerosis. Multiple Sclerosis Association of America website. Available at http://mymsaa. org/ms-information/overview/long-term-treatment. Accessed April 19, 2016.
- Farber RS, Sand IK. Optimizing the initial choice and timing of therapy in relapsing-remitting multiple sclerosis. Therapeutic Advances in Neurological Disorders. 2015;8(5):212-32. doi: 10.1177/1756285615598910.
- Giesser BS. Exercise in the management of persons with multiple sclerosis. Therapeutic Advances in Neurological Disorders. 2015;8(3):123-30. doi: 10.1177/1756285615576663.
- Heine M, van de Port I, Rietberg MB, van Wegen EE, Kwakkel G. Exercise therapy for fatigue in multiple sclerosis. Cochrane Database of Systematic Reviews. 2015;9:CD009956. doi: 10.1002/14651858.CD009956.pub2.
- Beer S, Khan F, Kesselring J. Rehabilitation interventions in multiple sclerosis: An overview. Journal of Neurology. 2012;259(9):1994-2008. doi: 10.1007/s00415-012-6577-4.
- NINDS Multiple Sclerosis Information Page. National Institute of Neurological Disorders and Stroke website. Available at: http://www.ninds.nih.gov/disorders/multiple_sclerosis/multiple_sclerosis.htm. (Accessed October 2010).
- About MS. The **National Multiple Sclerosis Society website. Available at:**http://www.nationalmssociety.org/about-multiple-sclerosis/index.aspx. (Accessed October 2010).
- Janssen Announces U.S. FDA Approval of PONVORY™ (ponesimod), an Oral Treatment for Adults with Relapsing Multiple Sclerosis Proven Superior to Aubagio® (teriflunomide) in Reducing Annual Relapses and Brain Lesions. Titusville, NJ: Janssen; March 19, 2021.
- Ponvory™ [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc; 2021.