May 22, 2018
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What the PCP needs to know about MS diagnosis, treatment, and adherence

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The American Academy of Neurology recently updated its guidelines on Multiple Sclerosis to recommend that physicians consider prescribing disease-modifying therapies for MS patients early in the disease process. With this emphasis on early treatment comes the necessity for the earliest possible detection and diagnosis. Often, the opportunity to notice the first signs of MS falls within the scope of primary care practice.

“Primary care physicians should be aware of warning signs that may indicate MS,” Patricia K. Coyle, MD, founder and director of the Multiple Sclerosis Comprehensive Care Center and Professor and Vice Chair (Clinical Affairs) of Neurology, Stony Brook University School of Medicine, told Healio Internal Medicine. “If they notice these early warning signs, they can make referrals to a neurologist, get the patient diagnosed early, and get appropriate MS patients started on treatment.”

In addition to playing this pivotal role in early detection and treatment, PCPs can assist their patients in managing MS through awareness of potential comorbidities, knowing about medication side effects, and emphasizing the importance of a wellness plan.

Suspecting MS

According to Bruce A. Cohen, MD, professor, Davee Department of Neurology and Clinical Neurological Sciences at Northwestern University’s Feinberg School of Medicine, presenting symptoms of MS would likely include some difficulty with balance, vision, strength or other symptoms related to the central nervous system.

In addition to playing this pivotal role in early detection and treatment, PCPs can assist their patients in managing MS through awareness of potential comorbidities, knowing about medication side effects, and emphasizing the importance of a wellness plan.
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“Most commonly, they would be occurring in a relatively young individual, someone in their 20s or 30s, although the disease is seen in older individuals as well,” he said. “The main initial features would be those that implicate the central nervous system.”

Robert A. Bermel

Additionally, MS is usually seen more frequently in women, with a 3:1 ratio of higher prevalence in female patients, according to Robert A. Bermel, MD, medical director of the Mellen Center for Multiple Sclerosis and Staff Neurologist at the Cleveland Clinic

Bermel said any new neurological symptom should raise suspicion of MS, but that nonspecific symptoms should not necessarily warrant referral for MS.

“If you do an internet search of MS symptoms, you’ll get a list of 100 different symptoms, and some of these are non-specific, such as fatigue or tingling in the feet,” he said. “We try to avoid every patient with fatigue getting a workup for MS, because it’s probably not MS.”

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Bermel noted that PCPs should have a higher level of suspicion in the presence of focal neurological symptoms. These might include vision loss in one eye, vertigo associated with imbalance, double vision, or one or both legs not working properly. Bermel described the onset of these symptoms as “subacute.”

“They don’t start in an instant the way a stroke typically does, and they don’t build up over months,” he said. “They tend to build up over a day or two, stick around for weeks, and then get better on their own. That subacute time course of a focal neurological symptom is one of the most useful features to keep in your mind as suspicious of MS.”
Cohen said a PCP who suspects MS in a patient could refer to a neurologist right away or begin some initial studies on their own.

“I think a lot of that depends on the comfort level of that particular physician with diseases of the nervous system,” he said. “There’s quite a long list of potential differential conditions that might have some of these symptoms. Some of these would be excluded by the pattern of the symptom or the potential association with systemic symptoms that might implicate other conditions. There are a number of common conditions of metabolic origin that a PCP might screen for.”

Coyle added that PCPs should also be aware of a second, more unusual form of MS presentation – primary progressive – that occurs in a different demographic.

“It’s typically seen in midlife, typically in the 40s,” she said. “It’s an equal sex ratio, so men are as likely to present as women. The individual will be presenting with a story of gradually worsening walking difficulty and having problems with their legs, or one leg.”

These symptoms will continue to progress, Coyle said, becoming worse over months to years.

“What they have is a progressive myelopathy, a spinal cord condition,” she said. “It’s important to recognize that that can represent progressive MS and should certainly be the basis for referral.”

The importance of wellness practices

After the PCP has taken the important first step in suspecting MS and referring a patient to a neurologist, there are still important responsibilities for the PCP after a diagnosis of MS is confirmed. Ongoing routine checkups are an important time to monitor a patient’s MS management and ensure that it is being optimized in combination with their overall care. Bermel said PCPs should encourage preventive practices or wellness plans to minimize MS attacks.

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“There’s a hierarchy of wellness practices that I talk to patients about and that I would like a primary care physician to reinforce,” he said. “These are really important for patients, more important than we’ve appreciated in the past.”

Bermel said these wellness practices include not smoking, controlling medical comorbidities, and taking supplemental vitamin D. He recommends that his MS patients take between 2,000 and 5,000 IUs of vitamin D per day, and that PCPs can play an important part in bolstering this recommendation.

“It’s really good if the primary care physician can check up on the adherence of that,” he said. “It reduces the risk of MS attacks. It helps if the PCP knows that it’s on a patient’s med list, understands why they’re taking it, and mentions it to them.”

Cohen said he recommends vitamin D not just to MS patients, but to their children.

“We tell people nowadays to put their kids on vitamin D,” he said. “There are several studies now that have shown an association, particularly in Caucasians, between the vitamin D levels and risk of later MS, so higher vitamin D levels in adolescence and young adulthood are associated with lower risk of MS.”

Cohen emphasized the importance of helping MS patients to quit smoking. He cited current scientific knowledge that tobacco smoking is associated with a risk for worsening MS, and possibly even acquiring MS.

“Certainly, the primary care physician can be engaged in helping people quit smoking, and this just adds one more motivation for patients to quit,” he said. “For a patient with MS, this is a big one that they are really able to influence.”

According to Coyle, emphasizing the need for these wellness practices is one of the most important actions a PCP can take in managing MS.

“It’s so important to counsel on not smoking, on healthy diet on being optimum body weight, and on doing regular exercise; these are things that promote brain health and combat MS,” she said. “Actually, you can see greater disability associated with not following these wellness practices.”

Bermel said in terms of exercise, he advises MS patients to do two different types of exercise, one of which is aerobic exercise. He said this could include brisk walking, running, biking, or swimming. For patients who might have some difficulty with mobility, he advises yoga or stretching exercises.

Awareness of comorbidities

MS is associated with various comorbidities, and it is an important job of the PCP to be aware of the potential for these comorbidities in their MS patients. According to Cohen, the MS population has a higher prevalence of CVD risk factors such as hypertension, hyperlipidemia, and diabetes.

“Addressing these comorbidities becomes important in this population because the effects are compounded in association with MS,” he said. “The PCP should recognize the importance of managing these conditions, not just because they’re important in and of themselves, but also because of their additive effects in people with MS.”

MS is also associated with mental health comorbidities like depression, anxiety and possibly stress. Because of these potential effects, Bermel said he thinks psychologists should be included as part of a complete MS management team.

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“Part of wellness is staying physically healthy, and part is staying mentally healthy and dealing with stress in an appropriate way,” he said, “So we tend to be pretty aggressive about linking in psychologists to help with stress management, and a PCP may have links to local referral sources for that.”

The current state of MS medications

Cohen said another essential but simple action PCPs can take to help their MS patients is to encourage them to take their MS medications.

“The biggest issue in a patient with relapsing MS is to take their medication regularly as prescribed,” he said. “That’s the single most effective thing that someone can do. Encouraging patients to adhere to their treatments is a great way for PCPs to help in management.”

According to Bermel, nearly all MS patients who have had recent disease activity should be on a disease-modifying therapy. He said disease-modifying therapies have been shown to reduce the risk of relapses, reduce the incidence of new MRI lesions, and, in many cases, slow disability progression.

“The evidence for their use is quite good,” he said, “and the newer disease-modifying therapies, those that have been available over the last 10 years, are in general more effective, better tolerated, and in many ways safer than the older, injectable disease-modifying therapies.”

Coyle said she groups disease-modifying therapies into three categories: needle injectables, oral medications, and monoclonal antibodies.

The needle injectables, which date back to the 1990s and include interferon betas and glatiramer acetates, are very safe, Coyle said. Oral medications would include fingolimod, teriflunomide, and dimethyl fumarate. The monoclonal antibodies are highly effective but may potentially be higher risk agents.

“What the neurologist is doing is trying to find the best fit for the individual patient, because at this point in time, we don’t have biomarkers to tell us what the best disease-modifying therapy is for an individual patient.”

Potential side effects

Cohen said the PCP’s role in a disease-modifying therapy regimen would not be as intricate as that of the neurologist but added that they should stay updated and aware of their patient’s medications and potential side effects.

“In general, I think what the primary physician would want to do with respect to the disease-modifying therapy would be to know which therapy their patient was on and have some awareness of the common side effects of that agent, so that if the patient presented with some of those symptoms, they might connect it to the medication,” he said.

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One common situation can occur if a patient with MS develops an infection. Cohen said in these patients, infection can make them weaker and lead to a re-emergence of MS symptoms. He said this can occur because the comorbid condition is causing increased physiologic stress on the nervous system, which can prompt the appearance of relapse.

“We refer to this as a pseudo-relapse, and the key element here is that the treatment for this is usually that of the underlying condition, and this doesn’t necessarily represent an MS attack,” he said. “It’s useful for PCPs to know that treating the underlying condition is all that’s necessary, rather than automatically giving the patient steroids.”

According to Bermel, some MS medications can affect blood count levels, so the PCP should know about this side effect in patients with abnormal lab tests.

“If a PCP is checking routine labs and sees an abnormality such as low lymphocyte counts or elevated liver function tests, and that patient is on an MS therapy, I would recommend that they discuss that with the patient’s neurologist to see if that’s an expected consequence of the therapy,” he said. “Some of these drugs will lower lymphocyte counts, but if that’s related to the mechanism of action and is expected, it’s not a problem.”

Genetic concerns?

In the ongoing treatment of MS patients and possibly their families, PCPs may wonder how concerned to be about the children of the patient with MS. Bermel said overall, this is not a factor PCPs need to focus on unless there is a direct cause for concern.

“MS does have some genetic components to its risk,” he said. “However, the risk of an MS patient’s children developing MS is still quite low – if the child has one parent with MS, the risk is between 3% and 5%. So that’s typically not something that should signal any alarm bells.”

Bermel said he does not typically screen children of MS patients with MRI scans. If the child of a patient with MS demonstrates new neurological symptoms, he said the PCP should refer to a neurologist.

Coyle said although there is a slightly increased risk in children with a first-degree relative with MS, it is not an inherited disease.

“There is no gene that passes on MS – that’s the first thing to understand,” she said. “We inherit large sets of genes that may be enriched for risk susceptibility genes, and perhaps be poorer in protection genes. However, people can really be assured that there is no gene that will pass on the disease to their children.” - by Jennifer Byrne

For More Information:

Patricia K. Coyle, MD, can be reached at the Department of Neurology, Stony Brook University Medical Center, Stony Brook, NY 11794; email: Patricia.Coyle@stonybrookmedicine.edu.

Robert Bermel, MD, can be reached at 9500 Euclid Ave., Cleveland, OH 44106; email: BERMELR@ccf.org.

Bruce A. Cohen, MD, can be reached at 710 N. Lake Shore Dr., Abbott Hall, 1121, Chicago, IL 60611; email: bac106@northwestern.edu.

Disclosures: Coyle reports consultancy for Accordant, Acorda, Bayer, Biogen, Celgene, Genentech Roche, Genzyme/Sanofi, Novartis, Serono and Teveno and conducting clinical trials sponsored by Actelion, Genentech Roche, MedDay, NINDS and Novartis. Bermel reports no relevant disclosures. Cohen reports serving as a consultant for EMD Serono and Novartis, and conducting clinical trials sponsored by Genentech, Novartis and Biogen IDIC.