The summer of 2020 couldn’t have gotten any more intense for Mike Witherite—until it did. Like every other American, he and his family were dealing with the uncertainty and restrictions of the COVID-19 pandemic. On top of that, as CFO of Teton Science Schools, an educational nonprofit, Witherite was also responsible for paying 150 employees during a rough economic time. “I was working all day, going to bed at midnight, and waking up at 5 or 6 a.m. and starting again,” says Witherite, 48, a father of two teens who lives with his family in Victor, ID. Then, in early June, while descending the last two steps from his home office above his garage, his left side seized up in pain and became paralyzed, and he crumpled to the floor. “I thought I was having a stroke,” he says. “It was one of those horrible end-of-life moments where you think, ‘I hope my kids don’t find me.’”
Yet in less than two minutes, Witherite regained his mobility. Still feeling tingly and numb, he was able to walk into the house and tell his physician assistant wife what had happened; she immediately drove him to their small county hospital. “There was no MRI machine, but the doctors ruled out a stroke and heart attack right away,” says Witherite.

The couple was sent home, but when Witherite had a similar attack of paralysis the next day, his wife drove him to a bigger hospital an hour away, where he had an MRI. “They found lesions on my brain, and that’s when the doctor told me I probably had multiple sclerosis.”

Possible Causes

In an autoimmune disease like multiple sclerosis (MS), activated immune cells invade the central nervous system and cause inflammation, neurodegeneration, and tissue damage. The immune system turns on the body instead of protecting it. A study in the 2019 issue of Neurology estimated that in 2017, nearly 1 million adults in the United States have the disease. The majority are women, who are almost three times more likely to develop MS than men.

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The prototypical patient is a young white woman in her twenties or thirties. Most studies indicate that MS is more common among women of Northern European ancestry. Even though men and people of color tend to be affected less often, they may have a different clinical course. Experts agree that more studies of underrepresented groups such as African Americans and Hispanics are needed to understand how the disease manifests in these populations and how patients respond to treatment.

Various studies have explored whether sex hormones play a role in the gender disparity, and there’s also genetic factors to consider: Having a first-degree relative with MS—a parent or a sibling—increases the risk of getting the condition, but there is no single MS gene. Experts believe that a combination of genetic susceptibility and environmental factors are likely to blame. “Some genes that affect immune function seem to be overrepresented in MS patients, but there are also environmental factors, whether a viral infection or low vitamin D or something else we haven’t figured out yet,” says Aaron E. Miller, MD, FAAN, medical director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis at the Icahn School of Medicine at Mount Sinai in New York City.

While the origins of MS are still murky, experts now have a clearer sense of what triggers the attacks. Normally, the brain is mostly impenetrable to immune cells, but with MS, they gain entry into the central nervous system and attack the myelin sheath. Myelin is an insulating material that covers the nerves of the brain, spinal cord, and the optic nerve, protecting and enabling them to conduct electrical and chemical impulses smoothly and efficiently.

Once immune cells attack the myelin, they may leave sections of the nerve exposed, like a frayed wire, or even damage the nerve fiber (“axon”) itself, which interferes with or blocks electrical transmission. The range of symptoms this can cause include fatigue (the most commonly reported symptom, affecting up to 90 percent of patients), numbness and tingling, vision disturbances, impaired balance, muscle weakness and tightness (spasticity), sexual dysfunction, bladder problems, cognitive changes, and mood disorders such as depression and anxiety.

Getting a Diagnosis

Delays and misdiagnoses are common with MS because there is no definitive test for it and because many other conditions can mimic the clinical and MRI findings. In fact, a 2019 study in Multiple Sclerosis & Related Disorders found that 18 percent of new patients seen in two large academic MS clinics had been referred with a misdiagnosis of MS.

Typically, patients experiencing symptoms will undergo a neurologic exam and have an MRI of the brain and spinal cord with gadolinium, a substance that helps identify active inflammation. Doctors look for white spots—or lesions—on the brain and in the spinal cord. These spots represent nerve damage, resulting from a combination of swelling, inflammation, demyelination, and damage to the nerve axon itself. Other tests may be conducted to look for further evidence of damage in the central nervous system and to rule out other conditions, or MS mimics.

While that sounds definitive, it’s not uncommon for people to show white spots on an MRI and not have MS, says Brian Weinshenker, MD, FAAN, professor of neurology at Mayo Clinic. Many other conditions can produce lesions on MRI. In addition, other conditions can cause symptoms similar to MS such as numbness and weakness, including fibromyalgia, migraine, some infections, other inflammatory conditions, and even psychological conditions.

If there is doubt, Dr. Weinshenker recommends getting a lumbar puncture to help confirm the diagnosis even though 5 to 10 percent of patients, won’t show evidence of the disease in their cerebrospinal fluid. “There are certain symptoms that are very suggestive of MS—a tingling up and down the spine when putting your chin to your chest (known as Lhermitte’s sign) or eye pain followed by vision loss,” he says. In the absence of those, “we try to determine whether patients have a reliable diagnosis of MS before telling them they have the disease and putting them on medication when they don’t need it,” he says.

Neurologists also may reference the McDonald Criteria, which include objective evidence of nervous system damage in more than one area and at least two attacks that produce symptoms or the presence of both inflamed and non-inflamed lesions on an initial MRI as well as ruling out other possible causes. “For most patients, diagnosis is very straight forward. It’s only in a minority of patients—but an important minority—that the diagnosis is not clear at all,” emphasizes Dr. Weinshenker. In cases where the diagnosis or treatment plan is in doubt, it may be worth scheduling a consultation with a neurologist who specializes in MS.

In Witherite’s case, his diagnosis was confirmed at the University of Utah Hospital, five hours away from his home, where he spent two nights and was prescribed steroids to reduce inflammation. His initial attack was unusual for its rapid onset, but doctors now believe he likely had MS for years beforehand, starting with less acute symptoms. “I’ve worn glasses to correct double vision for 15 years, which my ophthalmologist attributed to weak eye muscles, but which we now think is from the MS,” he says. And four years ago, after tearing an Achilles tendon, his ankle never healed properly. “I’ve been living with a dropped foot since then, and my whole right leg is weak, but I’ve always explained it away as an athletic injury. Plus, in the past six months, I’ve lost muscle mass and have had stiffness and spasms in my hip.” In some ways, his diagnosis has been a relief. It explains why his physical capabilities have been declining. “At least now I know there is something I can do about it,” he says.

While MS is unlikely to affect lifespan, it can affect life decisions. This is especially true for newly diagnosed young women who want to start a family. “Women generally have to discontinue treatment during their pregnancy, but they tend to have fewer attacks at that time,” says Dr. Miller. “MS represents an overactive immune system, and during pregnancy the immune system is dialed down.” Additionally, he says, no data indicate that having children is associated with increased long-term disability in women with MS.

Treatment Options

Since 1993 when the first disease-modifying therapy—interferon beta 1-b—was approved by the US Food and Drug Administration (FDA) for MS, the number of approved medications has increased to almost 20. Although they can’t cure the disease, the drugs alter the course of it and reduce the number of attacks, leading to less disability over time.

All MS medications work by altering the immune system in some way so it doesn’t turn on the body and damage myelin and nerves. “Think of it like a three-legged stool—the treatments disrupt one of the ‘legs’ or immune cells, whether the B-cells or T-cells or macrophages—until the stool falls over,” explains Tanuja Chitnis, MD, FAAN, professor of neurology at Harvard Medical School in Boston. With so many options, deciding on which one requires “a long conversation between doctor and patient,” says Fred D. Lublin, MD, FAAN, director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis at the Icahn School of Medicine at Mount Sinai in New York City. “The decision is unique to every patient, and both doctor and patient should consider several options depending on the neurologist’s assessment of severity and prognosis.”

Personal preference comes into play, too: Some therapies are taken orally, others are infused intravenously, and some are injected. “Maybe you prefer pills to injections, or you don’t want to do the infusions,” says Dr. Chitnis. (For a list of the current drugs, see “Disease-modifying Therapies for Multiple Sclerosis" below.)

Regardless of preference, the important point is to start therapy as soon as possible. “One of the very powerful things we’ve learned from MRIs is that even when patients feel well and there are no symptoms, there’s a good chance the disease is still active,” explains Dr. Miller. “That’s why we recommend treatment as soon as the diagnosis is confirmed.” And while people might not have to take medication for life, “I suggest that every patient take medication for 10 to 15 years, when the disease may still be causing damage,” says Dr. Chitnis. “You might feel fine when you’re 20 or 25, but every attack is like a hit to the brain, and every hit adds up. As patients get older, attacks become less frequent, but earlier attacks can cause disability later. The brain has fewer compensatory mechanisms as we age. As it becomes more dysregulated, that’s when progression occurs.”

When determining treatment, neurologists consider one of two approaches: early aggressive or gradually escalating. In the first, doctors start with one of the more potent drugs to minimize the number of attacks immediately and reduce the chances of progression and disability later in life. Some of these newer drugs may be riskier and come with an increased chance of infection, says Dr. Lublin. “But we take those things into consideration.”

In the second approach, doctors start with one of the older and more tested but perhaps less potent medications. If those don’t minimize attacks, patients might switch to something more potent.

Two randomized trials known as TREAT MS, and DELIVER MS are looking at whether newly diagnosed patients do better if they are treated with the most aggressive drugs from the start. “The choice is absolutely not one-size-fits-all,” says Dr. Miller, “but depending on the results of these trials, this could be an important breakthrough in the approach to MS therapeutics.”

Two-and-a-half months after his initial diagnosis, Witherite had his first IV infusion with one of the more potent medications, given twice yearly. “My doctor told me that there’s a good chance of a favorable outcome,” he says.

The Importance of Self-Care

“The best way to manage MS is with a combination of disease-modifying treatment, symptom management, rehabilitative strategies, and healthy lifestyle habits,” says Dr. Miller. Physical activity has been shown to have beneficial effects on symptoms and function, and it may improve immune dysfunction as well. Guidelines published in Multiple Sclerosis Journal in April 2020 suggest working up to a minimum of 150 minutes of exercise and/or physical activity per week, ideally a mix of aerobic, resistance, and skill-based neuromotor activities like dance or tai chi, that involve a combination of gait, balance, agility, and hand-eye-coordination.

Stretching, too, is especially crucial and can help alleviate muscle spasms, adds Dr. Chitnis, who advises her patients to stretch every day, twice a day, for at least 10 minutes. For painful or uncontrollable stiffness or spasms, muscle relaxants may help.

“If walking is difficult, work on gait or balance with a physical therapist, or strengthen specific muscles that have been weakened,” says Dr. Chitnis. “But you don’t want to overdo it or push yourself in ways that could lead to falls, especially during a time when so many of us are confined to our homes alone.” Overheating is another concern as it can trigger symptoms; be sure to have ice water handy or even wear a cooling collar—a flexible ice pack that attaches with Velcro—if the weather is especially warm, Dr. Chitnis advises.

For fatigue, MS specialists recommend exercise, caffeine, and power naps, and say a consultation with a rehabilitation health care professional for energy conservation strategies could be helpful. They also suggests ruling out thyroid problems, other medical conditions that could cause fatigue, and sleep disorders. In fact, sleep disorders are more common in people with MS than the general population. Limiting refined carbohydrates, which can spike blood sugar and lead to an energy crash, is also recommended. Specific medications can help with fatigue, and other drugs can treat energy-draining symptoms such as muscle weakness and spasticity, depression, pain, sexual dysfunction, insomnia, and bladder or bowel dysfunction, though many come with side effects of their own.

“Medications to control MS symptoms should be used sparingly,” cautions Dr. Weinshenker. “Some for fatigue, for instance, can impair sleep while drugs for bladder problems can cause dry mouth or confusion, so discuss the pros and cons with your doctor. It is often better to use nonpharmacologic measures such as stretching for spasticity and rest periods and fitness to manage fatigue.”

Not enough evidence exists to prove that diet can ease symptoms, says Dr. Lublin. But a healthy diet can improve or prevent other co-existing conditions such as diabetes, hypertension, or hardening of the arteries, which lead to poorer neurologic outcomes in people with MS. He and other experts recommend avoiding processed foods and saturated fats and eating plenty of fruits and vegetables. It’s also important to get enough vitamin D. A round-up of studies in the June 2018 issue of Neurology and Therapy found that low vitamin D levels may affect the onset of MS and its progression. “It’s important to optimize vitamin D levels—keep them in the normal range—and also get out into the sun,” says Dr. Chitnis.

And the evidence strongly suggests that smoking is a risk factor for both getting MS and promoting disease progression. The message from neurologists? Quit smoking.

Mike Witherite says he “aggressively overhauled” his habits in the two months since his diagnosis. “I’ve cut out sugar, alcohol, saturated fats, and processed foods, and lost 15 pounds. I feel much better.” He is also doing physical therapy for his foot and exercises at least four times a week. And though things remain stressful at work because of the pandemic, “I do whatever I can to get eight hours of sleep—no more going to bed at midnight.”

Managing Mental Health

Fifty percent of people with MS experience depression and 30 percent report anxiety, says Dr. Chitnis. She and other experts recommend psychotherapy and, if necessary, medication. “It’s important to recognize these issues and treat them,” says Dr. Miller, “especially because depression and anxiety can worsen symptoms like fatigue and cognitive problems.”

Witherite recalls a day of uncontrollable sobbing after his diagnosis. “I’ve never experienced tears like that. It was like going through all the stages of grief at once. I had all these feelings like ‘How did this happen?’ and ‘Why me?’ I didn’t even feel like I was in my body,”
he says.

He has since relied on meditation to quiet his mind. He also makes a point of being kind to himself and controlling his expectations. “I don’t get down on myself if I don’t feel up to doing something.” Ultimately, it’s about mindset, he says. “You can be better or bitter—and there’s no joy in being bitter. Though the diagnosis is still a shock, I feel better every day—and I try to be the most positive person in the house.”

That positive attitude is warranted. “The outlook for having a normal life and doing all the things you’d expect to do—work, exercise, having a family—is extremely good,” says Dr. Lublin. “This disease can be serious and disabling, but most of the time now, it’s not. The outlook is much brighter.” 

How to Choose a Medication

It’s helpful to keep these criteria in mind when talking with your physician about the various treatment options for multiple sclerosis, says Tanuja Chitnis, MD, FAAN, professor of neurology at Harvard Medical School in Boston.

Age: “Younger patients tend to have a higher relapse rate than older patients, which is a reason to begin treatment early,” says Dr. Chitnis. “Over time, the immune system changes and becomes less aggressive, leading to fewer attacks.”

Attack or relapse characteristics: “An episode that involves the spinal cord or causes difficulty walking or moving, tends to be associated with a more severe course of disease, versus sensory symptoms like numbness or tingling,” says Dr. Chitnis.

Relapse recovery: “After the first or second relapse, patients usually recover and things go back to normal in a few months, but if you haven’t had a full recovery, you might want a more aggressive treatment.”

Lesions: “If you have a lot of lesions, I might be more worried,” Dr. Chitnis says. “even if you don’t have that many, but they are in a sensitive part of the brain like the stem or in the spinal cord—that might merit more aggressive treatment.”

Disease-modifying Therapies for Multiple Sclerosis

Patients diagnosed with multiple sclerosis have more treatments than ever these days.

Oral agents

• Cladribine (Mavenclad)
• Dimethyl fumarate (Tecfidera)
• Diroximel fumarate (Vumerity)
• Fingolimod (Gilenya)
• Ozanimod (Zeposia)
• Siponimod (Mayzent)
• Teriflunomide (Aubagio)

Infusions

• Alemtuzumab (Lemtrada)
• Natalizumab (Tysabri)
• Ocrelizumab (Ocrevus)

Injections

• Glatiramer acetate (Copaxone, glatiramer acetate, Glatopa)
• Interferon beta-1a (Avonex, Rebif)
• Interferon beta-1b (Betaseron, Extavia)
• Ofatumumab (Kesimpta)
• Pegylated Interferon beta-1a (Plegrid)

Important Resources

• Brain & Life Multiple Sclerosis Overview
• Multiple Sclerosis Association of America: mymsaa.org; 800-532-7667
• National Institute of Neurological Disorders and Stroke: ninds.nih.gov; 800-352-9424
• National Multiple Sclerosis Society: nationalmssociety.org; 800-344-4867
• Navigating Life with Multiple Sclerosis by Kathleen Costello, MS, ANP-BC, MSCN; Ben W. Thrower, MD; and Barbara S. Giesser, MD, FAAN (Oxford University Press)