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For Your Patients-Acute Disseminated Encephalomyelitis

MOG Antibody Status Predicts the Risk of Relapse for ADEM

Robinson, Richard

doi: 10.1097/01.NT.0000546219.97617.dc
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Patients with acute disseminated encephalomyelitis who have MOG antibodies tend to have a higher risk of relapse than those with aquaporin antibodies, but they tend to have much better outcomes with full to near-full recovery, according to a new report.

For the patient with acute disseminated encephalomyelitis (ADEM) who tests positive for antibodies against myelin oligodendrocyte glycoprotein (MOG), what is the likely prognosis? A new long-term follow-up study of more than 50 antibody-positive ADEM patients suggests that the answer depends on whether the antibodies persist after the initial attack.

“We found that if MOG antibodies remain positive six months to a year after the initial attack, that is highly predictive of a relapsing course,” said senior study author Sean J. Pittock, MD, professor of neurology and director of the Center for Multiple Sclerosis and Autoimmune Neurology at Mayo Clinic in Rochester, MN. “If they drop off within three to six months, those patients have a much lower frequency of later attacks.”

The finding is important, independent experts said, because it can help inform the choice of whether to begin an ADEM patient on chronic immune suppression, or to watch and wait. The study was published July 16 online edition of JAMA Neurology.

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To perform the study, Dr. Pittock, first author Sebastian López-Chiriboga, MD, a fellow in autoimmune neurology at Mayo Clinic, and colleagues analyzed records from 264 patients with a history of ADEM, collected over 27 years, of whom 51 had initial and follow-up serum samples available to determine the presence of persistent antibodies.

Of the 31 children in the study, eight of nine with persistent MOG antibodies had a relapsing disease course. Four children in the study had transient antibodies, none of whom had a relapse. Eight of 20 adults in the study with persistent MOG antibodies relapsed while one of four adults with transient antibodies relapsed.

Of the remaining patients, one child and one adult had antibodies to aquaporin-4, also known to cause ADEM. Seventeen children and seven adults were negative for both antibodies.

Among the eight antibody-positive children who relapsed, there were a total of 22 relapses, from one to six per patient, during a median follow-up period of more than six years. Among the seven antibody-positive relapsing adults, there were 29 relapses, from three to six per patient, during a follow-up of more than three years. Clinically, relapses encompassed the spectrum of MOG-associated disorders, including ADEM, optic neuritis, transverse myelitis, and various combinations of these.

For children, the hazard ratio for those with persistent MOG antibodies was 3.1 (95% confidence interval 1.1-8.9, p=0.04) versus those without persistent antibodies. For adults, it was 5.5 (95% CI 1.4-22.5, p=0.02).

Based on these data, the Mayo team calculated that 80 percent of children and 70 percent of adults with persistent MOG antibodies would be expected to relapse within two years of an initial ADEM event, versus no children and 20 percent of adults with transient antibodies. “These data can be used to help inform treatment decisions,” he said, although there are still important unanswered questions.

“For patients who have an attack associated with aquaporin antibodies, we would immediately start them on an immunosuppressive medication to prevent another attack, because attacks in aquaporin autoimmunity cause significant disability,” Dr. Pittock said. “But with MOG antibodies, the situation is not as clear.”

Patients with MOG antibodies tend to have a higher risk of relapse than those with aquaporin antibodies, he said, but they tend to have much better outcomes nonetheless, with full to near-full recovery.

“The question for an ADEM patient in the context of MOG antibodies is whether to put the patient on immunosuppression. My tendency would be to recheck their antibody status in six months to a year,” Dr. Pittock said. “If they are negative, I would not recommend immunosuppression, because we see a very small risk of relapse. If they remain positive, my tendency would be to watch that patient carefully, and treat any attack aggressively, and then think of whether to recommend maintenance immunosuppression therapy, after a second event.”

On the other hand, if the patient has had a severe attack, and does not experience a full recovery, Dr. Pittock said, one might consider beginning immunosuppression, although the benefits of this strategy have not been rigorously tested. “At the end of the day, we don't have the data to answer that question. That's the study we need to do.”

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“This is an important study, and a good next step in understanding the course of MOG-associated ADEM,” commented Tanuja Chitnis, MD, FAAN, professor of neurology at Harvard Medical School and Brigham and Women's Hospital in Boston. “We ultimately need a larger cohort, perhaps 100 patients, ideally followed for up to 10 years, to truly be confident in deciding who should be treated with chronic immunotherapy. The questions for the community are whether the risk of relapse decreases with treatment and which treatment is most appropriate. Those are open questions.”

In the interim, she recommended, “The general neurologist should do a test for MOG antibodies at the time of an attack, in both children and adults, and do a follow-up test in six months, and monitor annually for the next several years.”

If antibodies are persistent, referral to a specialist is appropriate, along with consideration of immunotherapy, she suggested.

Brenda Banwell, MD, FAAN, chief of the division of neurology at Children's Hospital of Philadelphia, stressed that while persistent antibodies do correlate with relapsing disease, “it is still not clear that the presence of antibodies alone, in a child who has had no clinical or MRI evidence of relapse, means the child should be started on immune suppressant therapy.”

Dr. Banwell noted that in other autoimmune diseases, including myasthenia gravis, persistent antibodies can be found in patients in full clinical remission who have stopped treatment. Is this true in MOG-associated diseases as well? “We don't know yet — this will require an international collaborative study.”

But if the patient has already relapsed, and has persistent antibodies, that more strongly argues for treatment, she said. “Unfortunately we don't yet know for how long treatment should continue, because we don't know the lifelong risk of relapse.”

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Dr. Pittock receives no royalties from the sale of tests performed in the neuroimmunology laboratory at Mayo Clinic, though Mayo Collaborative Services Inc does receive revenue from conducting the tests.

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•. López-Chiriboga AS, Majed M, Fryer J, et al Association of MOG-IgG serostatus with relapse after acute disseminated encephalomyelitis and proposed diagnostic criteria for MOG-IgG-associated disorders JAMA Neurol 2018; Epub 2018 Jul 16.
    © 2018 American Academy of Neurology