The NeurologyLive® Peer Exchange, “Treatment of Multiple Sclerosis Relapses” features a panel of experts in the diagnosis and treatment of multiple sclerosis.
Moderator: Stephen Krieger, MD; Panelists: Joseph R. Berger, MD; Robert Bermel, MD; Samuel Hunter, MD, PhD; Amy Perrin Ross, APN, MSN, CNRN, MSCN
Watch the full Peer Exchange here.

Stephen Krieger, MDStephen Krieger, MD
Multiple sclerosis (MS) is characterized by its disease activity, referred to as relapses or exacerbations, in which demyelination and degeneration of the central nervous system results in a number of clinical symptoms, including optic neuritis, fatigue, and balance issues. MS specialists such as Stephen Krieger, MD, associate professor of neurology at the Icahn School of Medicine at Mount Sinai in New York, New York, are tasked with navigating these events to help prevent further neurologic damage. In a recent NeurologyLive® Peer Exchange discussion, Kreiger led a group of experts in an exploration of the state of treatment for MS relapses, offering insight into the prognostic value of relapse, as well as the goals of therapy and an overview of a new treatment algorithm for the evaluation, management, and response assessment introduced at the Consortium of Multiple Sclerosis Centers (CMSC) annual meeting. 
Prognostic Importance of Relapse 
Although preventing disease relapse is a goal of MS treatment, these events offer physicians the opportunity to divulge further information about their patients’ expected disease activity. Samuel F. Hunter, MD, PhD, president of Advanced Neurosciences Institute, began by defining relapse as the clinical correlate of inflammation in an important pathway in the nervous system. Most of the symptoms of MS, Hunter explained, are the result of very small abnormalities in new or old lesions in pathways—the optic nerve, brainstem, and spinal cord. 

“Now we have ways of looking at prognosis from a prospective point of view and ways in retrospective,” he said. “Prospectively, we know that pyramidal and cerebellar are more disabling relapses in practice. Things that involve the bladder probably are, as well. It takes much more severe sensory or visual deficit to be quite disabling, and we have a hard time measuring cognition, but it’s often along for the ride with these others.” 

Hunter noted that although physicians cannot anticipate the postrelapse improvement that patients will experience until long after, it is important to explain the nature of these events to patients. “There’s a huge difference in how well people recover when they’re on treatment and they’re treated versus when they’re not on treatment and they’re not treated, as well as when they’re treated [but not on treatment],” he said. 

The management of MS with disease-modifying therapies (DMTs) is backed by clear, evidence-based research; however, it wasn’t always this way, as Amy Perrin Ross, MSN, MSCN, APN, CNRN, neuroscience program coordinator at Loyola University Medical Center in Maywood, Illinois, said. 

“Back in those days—even before we had DMTs, or when we had some of the early ones but didn’t think our patients were ‘bad enough’ to use them—all we could do for our patients was treat relapses, and we would treat everything that came along,” from intense symptoms to a tingling sensation, she said. “We were aghast if patients chose not to have treatment back then.” 

In recent years, she said, controversy developed around the treatment of relapses: Do they matter? “They do from an inflammatory perspective in the ultimate outcome. They really do,” Perrin Ross said. 

Goals of Treating Relapse 
The panel next turned toward the ultimate aim of tending to relapse. Because most patients are visiting their MS specialist or neurologist when symptoms present, the physician’s first steps involve assessing the starting point, its status and severity related to worsening, how it compares with prior relapse, and the best approach to treating it. 

“What I have to ask myself is ‘How bad is this going to get? Is this something where patients have a very great deal of discomfort because of the nature of the event?’” Hunter said. “It’s really not a disabling sensory event. It might be painful. It might require symptomatic treatment. But to resolve the event unless it’s really quite exclusively painful, you may need to do nothing except to treat it symptomatically.” 

Although the symptoms of benign relapses, such as vision issues or vertigo, may be unpleasant, other symptoms, such as those affecting the legs and the bladder, can signal a more serious event. If injury or occupational disability is possible, the goal is to treat the symptom fully and effectively. 

For Joseph Berger, MD, associate chief of the Multiple Sclerosis Division and professor of neurology at Penn Medicine in Philadelphia, Pennsylvania, relapse signifies active disease, making its identification imperative. “Whether you treat the relapse or not, you know that disease is active and [that] whatever you’re doing for the patient at that point in time is simply not working, and it may lead to a change in the disease-modifying therapy that you’re using,” he said. 

Berger noted the common misperception that because patients appear to improve following relapse, they’ve returned to baseline. Using as an example the results of the 2008 Optic Neuritis Treatment Trial,1 in which a majority of patients maintained impaired visual acuity in the short and long term, Berger noted that perhaps just half of patients actually improve—and those who do not may not recognize it. “But if you look hard enough, you find that there’s an abnormality,” he said. “If the treatments that we have for relapses are effective in eliminating that inflammation, it likely has a role in decreasing whatever permanent damage is left.” 

Krieger added that, in order to develop more sensitive measurement methods, the field is moving toward paying closer attention to subtle findings, either of or from a relapse. Robert Bermel, MD, director of the Mellen Center for Multiple Sclerosis at Cleveland Clinic in Ohio, said that one of the more important points in identifying relapses involves giving patients anticipatory guidance. 

“One of the questions that many patients have and only a few of them ask is ‘What should I call the doctor for? What sorts of symptoms should worry me?’” Bermel said. “I think even just a minute or so of conversation with a patient who’s newly diagnosed in an exam room is important, to reassure them and tell them that most patients’ relapses do not occur 3 times a week [and] do not occur once a month. They’re an infrequent event, and they’re neurological symptoms that last longer than 24 hours, and we need to tell them that we’re available, and if they’re having any symptom that lasts longer than 24 hours, they should call us about it.” 

Bermel said that monitoring patients’ neuro-performance over time on a number of domains of neurological function can help determine if deviations are present. This allows physicians to unearth challenges that need to be addressed and alerts them to when patients need to be seen for possible treatment adjustments. 

At Cleveland Clinic, Bermel said, virtual visits offer a middle ground between a phone call and a clinic visit, especially for patients who are limited by disability or distance to the clinic. Using a video link, patients and providers can speak face-to-face for assessment. This successful feature of clinical management has become commonplace for him and his colleagues, he said. 

A New Algorithm for Treatment 
Another new feature of MS treatment is the CMSC treatment algorithm, which builds on the ARMS—Assessing Relapse in Multiple Sclerosis—a single-page resource to help physicians navigate MS relapse in a clear and concise way. Perrin Ross, who was part of the group that developed the tool, noted that keeping it short was a major focus to ensure its easy use. “We piloted it. We tested it for reliability and validity. We were able to assess those measures, and it’s been put into practice, and it’s available to anyone who wants to use it,” she said. “Fast-forward to the last year or so: A group of physician colleagues and advanced practice colleagues were convened to put together potentially a tool, or an algorithm, that could help guide us.” 

Estimates show that 66% of patients with MS do not get their regular care at an MS center. As Perrin Ross said, “They’re out there somewhere.” The new algorithm, she said, expands on the ARMS and gives physicians a 3-step process to help evaluate MS relapses. “It starts with evaluating the symptoms, just as we have talked about, and potential use of an MRI [magnetic resonance imaging] if and when it’s needed,” she explained. “Then we move on to step 2, which is looking at managing the relapse…and then, finally, step 3 is assessing the outcomes.” 

At this point, clinicians can use the ARMS, which includes a 1-month evaluation of the attempt to manage the relapse in question—which, in some cases, can be to watch and wait. Krieger then noted that managing a patient with MS requires more than simply evaluating and treating symptoms. Physicians should have a goal in mind at each step, have a rationale for their treatment decisions, and reevaluate the change or lack thereof. All 3 parts of the algorithm, Krieger explained, are essential to a sound, structured approach to MS management. 

“If you think about it, as with the virtual visits, we can give these— this 1-page tool—to our patients while they’re sitting in the waiting room,” Perrin Ross said. “We could do it over the phone to help us decide if it’s worth it for them to drive the 200 miles to come in and see us for this evaluation or maybe not. We could bring the patients in if we had that luxury, but it’s really meant to be done over the phone and so we have an idea of what our next step needs to be, so we don’t drop the ball after 1 course of steroids.” 

View the entire Peer Exchange, “Treatment of Multiple Sclerosis Relapses,” here.
1. Beck RW, Gal RL. Treatment of acute optic neuritis: a summary of findings from the optic neuritis treatment trial. Arch Ophthalmol. 2008;126(7):994-995. doi: 10.1001/archopht.126.7.994.