E.U. paediatric MOG consortium consensus: Part 1 – Classification of clinical phenotypes of paediatric myelin oligodendrocyte glycoprotein antibody-associated disorders

Abstract

Over the past few years, increasing interest in the role of autoantibodies against myelin oligodendrocyte glycoprotein (MOG-abs) as a new candidate biomarker in demyelinating central nervous system diseases has arisen. MOG-abs have now consistently been identified in a variety of demyelinating syndromes, with a predominance in paediatric patients. The clinical spectrum of these MOG-ab-associated disorders (MOGAD) is still expanding and differs between paediatric and adult patients. This first part of the Paediatric European Collaborative Consensus emphasises the diversity in clinical phenotypes associated with MOG-abs in paediatric patients and discusses these associated clinical phenotypes in detail. Typical MOGAD presentations consist of demyelinating syndromes, including acute disseminated encephalomyelitis (ADEM) in younger, and optic neuritis (ON) and/or transverse myelitis (TM) in older children. A proportion of patients experience a relapsing disease course, presenting as ADEM followed by one or multiple episode(s) of ON (ADEM-ON), multiphasic disseminated encephalomyelitis (MDEM), relapsing ON (RON) or relapsing neuromyelitis optica spectrum disorders (NMOSD)-like syndromes. More recently, the disease spectrum has been expanded with clinical and radiological phenotypes including encephalitis-like, leukodystrophy-like, and other non-classifiable presentations. This review concludes with recommendations following expert consensus on serologic testing for MOG-abs in paediatric patients, the presence of which has consequences for long-term monitoring, relapse risk, treatments, and for counselling of patient and families. Furthermore, we propose a clinical classification of paediatric MOGAD with clinical definitions and key features. These are operational and need to be tested, however essential for future paediatric MOGAD studies.

E.U. paediatric MOG consortium consensus: Part 4 – Outcome of paediatric myelin oligodendrocyte glycoprotein antibody-associated disorders

“…More specific for paediatric MOGAD is the phenotypical diversity, and its correlation to outcome needs to be addressed. In addition to the frequent MOGAD clinical presentations of acute disseminated encephalomyelitis (ADEM), optic neuritis (ON) and transverse myelitis (TM), also other less typical and rare presentations such as MOG-ab-positive encephalitis-like and leukodystrophy-like phenotypes, and non-classifiable syndromes are seen [5]. Additionally, prevalence of these diverse phenotypes differs according to age: Clinical events in patients nine years or younger have been shown to be more likely to affect the brain, whereas in patients older than nine years clinical events are more likely to affect the optic nerve [11].…”

“…Regarding functional outcome, the MOGAD phenotype will likely determine the most affected domains; cognition in patients with ADEM phenotype, bladder and motor problems with TM phenotype, visual problems with ON phenotype and epilepsy with encephalitis-like phenotype. As the functional outcome will be highly dependent on the clinical phenotype, in future studies a standardised classification, as suggested in this special issue Part 1 [5], will be of importance in order to correctly predict outcome.…”

“…Over the last decade, our understanding of the role of antibodies against MOG (MOGabs) in acquired demyelinating syndromes (ADS) and autoimmune encephalitis (AE) in children and adults has increased [2e4]. The clinical spectrum of MOG-ab-positive disorders is wide and the term MOG-ab-associated disorders (MOGAD) is recommended to describe this spectrum of phenotypes [5]. Only in recent years studies have been published on MOG-ab status in prospective cohorts of children with ADS and AE, thus limiting the length of follow-up of many patients in these cohorts [4,6,7].…”

Editorial on EJPN focus section on E.U. paediatric MOG consortium consensus statements

“…In recent years, several paediatric monophasic and multiphasic immune-mediated acquired demyelinating syndromes (ADS) like acute disseminated encephalomyelitis, optic neuritis and transverse myelitis have been shown to be associated with the presence of antibodies targeting myelin oligodendrocyte glycoprotein (MOGab), a small yet important component of the myelin sheet [1]. As these MOG-ab-associated disorders (MOGAD) are rare and clinically diverse there is a need for consensus on both the clinical classification and management of these children, that is currently lacking.…”

“…Part 1 reviews the clinical features of the different monophasic and multiphasic clinical subtypes of paediatric MOGAD and introduces a clinical classification of MOGAD [1]. In part 2 the radiological features of these entities are delineated in addition to an overview of the differences between of the radiological features of paediatric MOGAD and other ADS like multiple sclerosis and aquaporin-4 mediated diseases [2].…”