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COVID-19: Guidelines for Myasthenia Gravis Management and other Neuromuscular Disorders

Article In Brief

A panel of experts on myasthenia gravis and Lambert-Eaton myasthenic syndrome pulled together a consensus document, based on what is known to date, on how to manage these neuromuscular diseases during the COVID19 pandemic.

If your patients have myasthenia gravis, should they come in for an infusion therapy? Is it safe to start patients on a new B-cell depleting therapy? And should patients stop their immunosuppressive therapies? As the COVID-19 pandemic rages on, neurologists working with patients with neuromuscular diseases are fielding these questions with little overall specific data on the overall effect of the virus on patients with these neuromuscular conditions.

In an effort to answer those questions based on what is known to date, a panel of experts has published new guidelines to treat myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) in the setting of the novel coronavirus.

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“We recommend that if an individual is stable on immunotherapy, that that therapy be continued without change, unless that change is dictated based on change in the underlying disease activity.”—DR. RICHARD J. NOWAK

The guidelines, published online March 25 in the Journal of the Neurological Sciences, emphasize that all treatment decisions should be individualized, that patients should not be taken off of immunosuppressive therapies over fear of increased infection risk, and that in clinic infusions or blood tests should be evaluated to determine if they can be postponed or moved to the home. The panel also recommended that telemedicine or telehealth visits should be used as much as possible instead of in-person visits and advised delaying initiation of B-cell depleting therapies.

“Much of what we put forth in the guidance communication is common sense, “but it is important to highlight, to ensure that physicians and patients aren't panicked due to lack of data or misinformation,” said Richard J. Nowak, MD, assistant professor of neurology at Yale University School of Medicine, and a member of the International Mg/COVID Working Group, which collaborated to develop the guidelines.

“The goal is to mitigate the potential for exposure to the virus for patients, without compromising care along the way,” Dr. Nowak told Neurology Today.

The guidelines were written by the recently formed International Mg/COVID-19 Working Group. The group was led by Saiju Jacob, MD, PhD, of the University Hospitals Birmingham in the United Kingdom; Srikanth Muppidi, MD, of Stanford University School of Medicine' and Dr. Nowak, who is director of the Yale MG Clinic. Other members of the group include MG experts from Denmark, Germany, Japan, Spain, and the United States.

The Working Group came together because patients were concerned about their risk of infection while on immunosuppressing drugs and the potential for serious complications due to disease-related muscle weakness.

“Many of our patients with myasthenia gravis are a special risk group, associated with a greater potential for COVID-19-related complications, beyond what is currently reported for age and other coexisting medical conditions,” Dr. Nowak said. “Having a neuromuscular comorbidity may significantly impact how an individual fares should they contract the infection.”

Because there are no data specifically about the effects of the virus on people with MG, the Working Group relied on their expertise in the development of these initial recommendations.

In addition to emphasizing national guidelines about handwashing, masking, and social distancing, the group offered 15 disease-specific recommendations. Above all, they said, patients should not discontinue current medications without consulting their physician. Additionally, there is no evidence to suggest that symptomatic therapies such as pyridostigmine place the patient at any increased risk. These therapies should not be discontinued unless there are other clinical reasons to do so, Dr. Nowak said.

While immunosuppressive treatments do increase risk of infection, the risk for disease exacerbation and worsening from stopping treatment or switching to symptomatic therapy only is significant. “We recommend that if an individual is stable on immunotherapy, that that therapy be continued without change, unless that change is dictated based on change in the underlying disease activity,” Dr. Nowak said.

“If you discontinue an immunotherapy, it can increase the risk of worsening the underlying illness or exacerbation, which can put the patient at even greater risk of having a COVID-related complication, should they contract it,” Dr. Nowak continued. “We want to be very clear, because that is the concern: Should patients on stable immunotherapy abruptly stop it and switch? The answer is no. We are not advising such changes simply because of the current pandemic as there are no data to support it.”

There is no evidence that infusion therapies such as intravenous immunoglobulin or plasma exchange increase COVID-19 risk, except if travel to an infusion center may expose the patient to the virus. Over the past two to three weeks, Dr. Nowak's center has been transitioning patients receiving these treatments to home infusion where possible. That process has presented challenges, both logistical and bureaucratic, “but we are taking it week by week, and doing our best to work through it,” he said.

Logistical challenges have included connecting patients with MyChart, part of the EPIC electronic records system, and making sure they have their computer system set up properly, he said. Reimbursement for telehealth visits has so far been going smoothly, Dr. Nowak noted, but it has required diligence in meeting the authorization requirements, he said, noting that Medicare has recently expanded access to telehealth in response to the pandemic.

Even more patients are receiving their regular follow-up appointments by telephone or video. During this same period, Dr. Nowak said, “We have switched essentially all of our patients to telehealth visits, unless the patient needs to be seen urgently.”

Patients whose treatments require regular blood work might be able to delay a scheduled lab visit if their values have been stable, he added. “This decision needs to be made on a case-by-case basis, with the risks and benefits of not doing or delaying a test considered in the context of infection risk.”

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“We are trying to emphasize how important social distancing guidelines are, to really avoid contact with others. We are also making sure that if they are on chronic corticosteroids, that they are not running out of medication, because that would be extremely dangerous. We make sure they are continuing to take it and try to reassure them that if they follow the general recommendations for infection avoidance, they should be fine.”—DR. EMMA CIAFALONI

The decision about whether to begin a B-cell depletion therapy warrants special consideration, the Working Group suggested, because of the possible greater risk of viral illness complications. “Patients doing well on such therapies are probably fine to remain on them,” Dr. Nowak said, but beginning such treatment during the pandemic “may not be advised, unless there are no alternatives. We do worry about complications in that particular patient group.”

Dr. Nowak's center has three MG patients who have contracted COVID-19, who by early April were still undergoing treatment for the virus. The Working Group is in the process of launching an international registry for such patients, to better understand the impact of COVID-19 on clinical course and outcomes, particularly mortality and morbidity.

“While we remain optimistic that in time there will be an effective vaccine, we won't be able to immunize every individual immediately, so we will need to gather data that can help in prioritizing patients once the vaccine is available,” Dr. Nowak said.

Expert Commentary

“These guidelines do a nice job of summarizing and bringing together in one place the sort of advice we are giving to our patients,” commented Michael G. Benatar, MD, PhD, FAAN, professor of neurology and public health sciences and chief of the neuromuscular division at the University of Miami Miller School of Medicine.

Dr. Benatar's colleague at the University of Miami, Volkan Granit, MD, assistant professor of neurology, added, in agreement with these proposed guidelines, “Our approach is to personally tailor advice to the individual needs of each patient. We tell our patients we think it would be wrong in most cases to stop their immunosuppressive treatment because their disease can be as problematic as the coronavirus.”

In the ALS clinic that Dr. Granit directs, “telemedicine was being used long before the pandemic arose, but only for patients who could not travel to the clinic. It has now become the default.”

“We have found multiple ways to examine a patient, often with the help of a loved one at home, for instance, to move the camera or to provide assistance to prevent falls,” Dr. Granit said. Video-based functional evaluations substituting for the standardized strength exam, for example. “We are getting almost uniformly satisfactory feedback from our patients for neuromuscular telehealth.”

COVID-19 disease is even more of a concern for patients with significantly compromised bulbar and respiratory function, such as those with ALS, Dr. Benatar noted. “I worry more about the impact of the illness on these patients, losing ground they may not be able to regain.”

Emma Ciafaloni, MD, FAAN, professor of neurology and pediatrics at the University of Rochester Medical Center, congratulated the Working Group on developing the guidelines, “because it is a rare disease and management of myasthenia patients may not be as familiar to the general practitioner.”

“These recommendations are a very good start,” Dr. Ciafaloni said. “It is anxiety-provoking for patients is to hear contradictory information, so to have a good reference developed by international experts is very reassuring.”

She agreed with the guidance that blood work might be postponed for a patient whose lab values appear unchanged over time, to decrease the risk of infection. Similarly, she said, if a patient on infusion therapy has been stable, it may be possible to delay a treatment session. New patients who have not yet begun therapy, if they are not too severely impaired, might be able to delay commencing immunosuppressive treatment as well.

“More concerning are those patients who are suffering exacerbations, or the 15 percent of patients who are refractory and require more frequent treatment. Those are the ones we are a little more concerned about,” she said.

Her clinic also sees many boys with Duchenne muscular dystrophy, and for those patients, she said, “We are trying to emphasize how important social distancing guidelines are, to really avoid contact with others. We are also making sure that if they are on chronic corticosteroids, that they are not running out of medication, because that would be extremely dangerous. We make sure they are continuing to take it and try to reassure them that if they follow the general recommendations for infection avoidance, they should be fine.”

Finally, Dr. Ciafaloni said, “In a time of uncertainty, with the added stress of the potential for viral infection, I would recommend that all general practitioners on the front line of treatment for neuromuscular patients to reach out as much as possible to the neuromuscular experts in the community. It is our function and our job to provide some guidance in such cases.”

Link Up for More Information

• Jacob S, Muppidi S, Guidon A, et al; for the International MG/COVID-19 Working Group. Guidance for the management of myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) during the COVID-19 pandemic https://www.jns-journal.com/article/S0022-510X(20)30139-8/fulltext. J Neurol Sci 2020: Epub 2020 Mar 25.
    • Zhao H, Shen D, Zhou H, et al. Guillain-Barré syndrome associated with SARS-CoV-2 infection: Causality or coincidence https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(20)30109-5/fulltext. Lancet Neurol 2020; Epub 2020 Apr 1.