A "milestone" discovery that an antibody is associated with a wider range of life-threatening autoimmune diseases than previously thought offers new hope for improved diagnosis and treatment in children with life-threatening neurologic disorders.
Results of a prospective study show myelin oligodendrocyte glycoprotein (MOG) antibodies are linked to multiple demyelinating disorders (including neuromyelitis and optica spectrum disorders) and encephalitis.
In addition, investigators found that 85% of children in the study who tested positive for MOG antibodies and received appropriate treatment had complete or near complete recovery.
Yet the diagnosis of many of these patients, especially those with encephalitis, would have been missed if it were not for the prospective design of the study, the investigators say.
"MOG antibody testing should be included in the initial workup of pediatric encephalitis, after excluding infectious causes or if the clinic-radiological features are different from anti-NMDAR encephalitis," lead investigators Thaís Armangue, MD, and Joseph Dalmau, MD, from University of Barcelona, Spain, told Medscape Medical News.
"This is important because there are patients with anti-MOG associated encephalitis who clinically and radiologically resemble viral encephalitis or other autoimmune encephalitis associated with antibodies against neuronal receptors — GABA-A receptor, or dopamine 2 receptor — and may have different treatment and prognosis," the investigators added.
The findings also point to the need to update the current classification and terminology of MOG antibody-associated syndromes, they noted.
The study was published online February 10 in Lancet Neurology.
Novel Investigation, Novel Findings
MOG antibodies damage the protective myelin sheath that surrounds nerve fibers in the brain, optic nerves, and spinal cord.
Over the past decade, the concept of inflammatory central nervous system (CNS) disease associated with MOG antibodies has evolved to include a variety of syndromes, but the entire spectrum of MOG antibody-associated syndromes in children is unknown.
The researchers conducted a prospective, observational study of 239 children with suspected demyelinating syndromes and 296 children with encephalitis other than acute disseminated encephalomyelitis (ADEM) at 40 hospitals across Spain.
In total, 116 (22%) of the 535 children tested positive for MOG antibodies, including 94 (39%) with demyelinating syndromes and 22 (7%) with autoimmune encephalitis. About one quarter of these children had syndromes not previously associated with MOG antibodies.
Presenting syndromes in children with MOG antibodies included ADEM (46 children, 68%), encephalitis other than ADEM (22 children, 19%), optic neuritis (20 children, 17%), myelitis (13 children, 11%), neuromyelitis optica spectrum disorders (6 children, 5%), and other disorders (9 children, 8%).
Among the cohort of patients with encephalitis other than ADEM, MOG antibodies were the most common autoantibodies, surpassing all neuronal antibodies combined.
"In the literature, there are a few case reports or small series, mainly focused in adult patients, indicating that MOG antibodies also can associate with encephalitis. Here we show in a large prospective cohort of children that MOG antibodies are the most frequent autoantibodies in patients with encephalitis," the researchers said.
The study also showed that the clinical presentation of MOG antibody-associated syndromes is age dependent, with acute disseminated encephalomyelitis predominant in young children and neuromyelitis optica (including optic neuritis or myelitis) predominant in older children.
During median follow-up of 42 months, 28% of children with MOG antibodies relapsed.
With appropriate treatment, 85% of all children with MOG antibody-associated syndromes had substantial recovery (Modified Rankin Scale [mRS] < 2). However, 15% experienced moderate to severe disease-related deficits (mRS > 2) and one died from their disease.
The study also revealed two pediatric phenotypes that are associated with a poor prognosis — bilateral cortical involvement and leukodystrophy-like features.
"Currently, we don't know why some patients develop these severe phenotypes and others [do] not, or why 15%-25% of patients with anti-MOG-associated disease develop a relapsing course," said the investigators.
"A better understanding of the factors that are associated with bad prognosis or a relapsing course will facilitate an early diagnosis and a more aggressive treatment approach," they added.
Writing in a linked commentary, Romain Marignier, MD, PhD, from Hôpital Neurologique Pierre Wertheimer in Lyon, France says this research is "a milestone in the understanding of MOG antibody-associated syndromes, as it showed that MOG antibodies are not restricted to demyelinating syndrome, but should also be considered in children presenting with encephalitis."
"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. 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," Marignier concludes.
This study was funded by Mutua Madrileña Foundation; ISCIII–Subdirección General de Evaluación y Fomento de la Investigación Sanitaria; Fondo Europeo de Desarrollo Regional; Pediatrics Spanish Society; Departament de Salut, Generalitat de Catalunya; Marato TV3 Foundation; Red Española de Esclerosis Múltiple; La Caixa Foundation; and Fundació CELLEX.
Armangue has received grants from Mutua Madrileña Foundation, ISCIII-EDER (Spain), Dodot Procter & Gamble, the Pediatrics Spanish Society, PERIS (Generalitat de Catalunya), Marato TV3 Foundation, Red Española de sclerosis múltiple, and Fundació CELLEX; personal fees and nonfinancial support from Novartis; and nonfinancial support from Roche. Dalmau has a patent with royalties paid to Athena Diagnostics, and patents with royalties paid to Euroimmun. Marignier has disclosed no relevant financial relationships.
Medscape Medical News © 2020
Cite this: 'Milestone' Discovery Offers Hope forLife-Threatening Neurologic Disorders - Medscape - Feb 12, 2020.