Diagnostic algorithm for relapsing demyelinating syndromes of the CNS in children

Abstract

BackgroundPaediatric relapsing demyelinating syndromes of the CNS define a group of diseases that have different phenotypes. Although for some of them, such as multiple sclerosis and neuromyelitis optica spectrum disorder (NMOSD), diagnostic criteria have been developed, diagnostic uncertainties are not uncommon. We aimed to identify the key features that unify phenotypes, and focused on patients with myelin oligodendrocyte glycoprotein (MOG) antibodies, to investigate whether they show distinctive clinical and radiological features, independently of their original diagnosis. We then generated a diagnostic algorithm for clinical use. MethodsWe reviewed the clinical characteristics, MOG and AQP4 antibodies, intrathecal oligoclonal bands, and Epstein-Barr virus serology results of 110 children with relapsing demyelinating syndromes. A neuroradiologist, masked to the diagnosis, scored the MRI scans. Clinical, radiological, and serological test results were compared between the different relapsing demyelinating syndromes. Findings62 children (56%) were diagnosed with multiple sclerosis, 27 (25%) with NMOSD, 14 (13%) with multiphasic disseminated encephalomyelitis (MDEM), and 7 (6%) with relapsing idiopathic optic neuritis (RION). Paediatric multiple sclerosis and NMOSD with AQP4 antibodies showed radiological and serological features typical of the respective adult phenotypes. Eight children with NMOSD (30%) were positive for AQP4 antibodies. MOG antibodies were found in 16 (83%) of 19 NMOSD patients without AQP4 antibodies, in all 14 children with MDEM, and in two with RION (33%). Children with MOG antibodies were younger, less likely to present with area postrema syndrome, had lower disability, longer time to relapse, and more cerebellar peduncle lesions than those with AQP4 antibody-positive NMOSD (all p<0·05). A diagnostic algorithm, applicable to any episode of CNS demyelination, led to four main relapsing demyelinating syndromes: multiple sclerosis, NMOSD with APQ4 antibodies, MOG-antibody-associated disease, and antibody-negative relapsing demyelinating syndrome. InterpretationUsing an integrative approach of clinical phenotyping, radiological analysis, and MOG and AQP4 antibodies, we were able to delineate patients to different disease phenotypes—namely, multiple sclerosis, MOG antibody spectrum disorder, and AQP4 antibody spectrum disorder. Although the clinical presentation can overlap (eg, optic neuritis and transverse myelitis) the pathogenic mechanisms are likely to be different. A correct diagnosis in children with non-multiple sclerosis phenotypes has both treatment and prognostic implications. FundingNational Institute for Health Research.