Pediatric MOG-Antibody-Associated Syndromes Include Encephalitis

By Will Boggs MD

February 18, 2020

NEW YORK (Reuters Health) - Pediatric myelin oligodendrocyte glycoprotein (MOG)-antibody-associated syndromes should be expanded beyond demyelinating syndromes to include encephalitis, according to a multicenter study.

"Our study provides a novel paradigm of including MOG antibodies as disease biomarkers not only of demyelinating diseases but also of encephalitis (even if the clinical and MRI features do not suggest a demyelinating disease)," Dr. Josep Dalmau of Universitat de Barcelona, in Spain, told Reuters Health by email.

MOG antibodies have been reported in association with optic neuritis, myelitis and acute disseminated encephalomyelitis (ADEM), which have a clinical course different from multiple sclerosis. The spectrum of disorders beyond these syndromes or encephalitis other than ADEM has not been assessed.

Dr. Dalmau and colleagues investigated the frequency and types of syndromes associated with MOG antibodies in two groups of children with acute demyelinating syndromes and encephalitis of any cause. They evaluated the distribution of disease onset and relapses, response to treatment and outcome, main immunological features, and pediatric phenotypes that were associated with poor prognosis among those with MOG antibodies.

Among 239 children with demyelinating syndromes, 39% had MOG antibodies, and among 170 children with encephalitis other than ADEM, 13% had MOG antibodies, the team reports in The Lancet Neurology.

In all patients, MOG antibodies were identified during an acute neurological event.

Among the 116 patients overall with MOG antibodies, 59% presented with clinical features of encephalitis; only two-thirds of these fulfilled criteria of ADEM.

At initial diagnosis 14% of MOG-antibody-positive patients were not treated, while 86% received first-line immunotherapy.

After a median follow-up of 42 months, only 17 of 100 patients diagnosed at disease onset had relapses. The likelihood of relapse was similar regardless of the type of syndrome at disease onset and did not differ between patients who received immunotherapy and those who did not.

Overall, 99 of the 116 patients (85%) had complete or near-complete recovery during follow-up, and 17 (15%) had moderate to severe deficits (one patient died during follow-up).

Of 93 children with abnormal MRI at disease onset, 65 had radiological follow-up that showed resolution of findings in 42 (65%) of these patients.

Patients with encephalitis other than ADEM had a higher frequency of poor outcome (8/42, 36%) than did patients with ADEM (6/46, 13%).

Poor-prognosis phenotypes included ADEM-like relapses progressing to leukodystrophy-like features and extensive cortical encephalitis progressing to atrophy.

The median time to become MOG-antibody-negative was 12 months for patients without relapses and 46 months for those with relapses. Conversely, 24% of patients who remained MOG-antibody-positive at six months developed relapses during the entire follow-up, compared with none of 20 patients who were antibody-negative at six months.

These findings carry two important messages, according to Dr. Dalmau. "First, in children, the occurrence of MOG antibodies and their use as disease biomarkers should not only be focused on acquired demyelinating syndromes but also in encephalitis, particularly after excluding infectious encephalitis and some of the most frequent or clinically recognizable causes of autoimmune encephalitis, such as anti-NMDAR encephalitis."

"The second message is that current criteria for MOG-antibody-associated demyelinating syndromes should be viewed with an open mind," he said. "As indicated, some of our patients did not fulfill criteria currently used for MOG-antibody-associated demyelinating syndromes."

"These two messages are important for diagnosis, prompt treatment, and also categorization of subphenotypes that are refractory to treatment," Dr. Dalmau said.

"In view of the very broad clinical spectrum now associated with MOG autoimmunity, the next challenge will be to identify the optimal therapeutic strategy for each clinical presentation," writes Dr. Romain Marignier from Hopital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, in France, in a linked editorial. "This objective is closely connected to a better understanding of the pathogenic role of MOG antibodies, and the need for early, robust, and specific prognostic factors of relapse and disability."

Dr. Thomas Berger from the Medical University of Vienna, who recently reviewed MOG-antibody-associated disorders, told Reuters Health by email, "Most interestingly, surprising, and clinically of utmost importance are the findings that anti-MOG antibodies are that prevalent in children with (autoimmune) encephalitis apart from ADEM, thus definitively expanding the clinical phenotypes associated with anti-MOG antibodies."

"In addition, it was highly important to learn that the vast majority of MOG-positive children recovered quite well, whereas those with poor outcome had clearly distinct clinical and/or MRI features," he said. "These seminal findings are a true milestone in the diagnostic spectrum and work-up of pediatric CNS demyelinating and encephalitic disorders."

"Physicians have to extend their differential diagnostic know-how and awareness for anti-MOG associated disorders within the spectrum of pediatric demyelinating CNS disorders and autoimmune encephalitis," said Dr. Berger, who was not involved in the study. "Anti-MOG antibodies need to be added to the current diagnostic work-up in such pediatric cases. However, it has to be emphasized that anti-MOG antibodies should be tested only in highly qualified and certified labs, because the sophisticated detection method for anti-MOG antibodies requires a high level of standardization and expertise."

"Finally," he said, "due to the complexity of the respective CNS disorders, it is in a given case nevertheless recommended to seek consultation with an experienced (neuropediatric) center."

SOURCE: and The Lancet Neurology, online February 10, 2020.