Myelin Oligodendrocyte Glycoprotein (MOG) antibody-related disorders (MOGAD) characterize clinically heterogeneous autoimmune diseases affecting the central nervous system (CNS) such as acute disseminated encephalomyelitis (ADEM), recurrent optic neuritis, transverse myelitis and neuromyelitis optica spectrum disorder (NMOSD). Estimated incidence in children is higher than in adults, around 0.3/100,000. Our Paediatrics-Neuroimmunology group have dealt with many pediatric patients with MOG antibody-associated demyelination over the last years. To gain better knowledge over the clinical course, best management and prognostic factors of this intriguing and rare disorder, we established a regional and national network to for data sharing, clinical confrontation and scientific dissemination. We focused on various clinical and laboratory aspects of MOGAD in children, though different multicentre Italian studies. We confirmed, as already reported in the most recent literature, that the clinical onset of MOGAD in children is usually ADEM, followed by ON (typically bilateral), while NMOSD features are more common in adolescents and adults. Similarly, oligoclonal bands are rare in MOGAD and progression to multiple sclerosis is exceptional. Nonetheless, a significant proportion of children with MOGAD experience clinical relapses, and these relapses are more common when MOG-antibody titers persist over time (after 3 to 6 months from the onset), regardless of the acute immunomodulatory treatment. We further recognized the main characteristics of MOG-associated optic neuritis, which are strongly associated with optic disc swelling and increased RFNL, and tend to recover better compared to seronegative optic neuritis. Starting from clinical experience and going through the international scientific literature, we managed to define seizures as an underreported phenotype of MOGAD: in particular, seizures occurred mostly in the context of a cortical encephalitis, or even presented as an isolated phenomenon in patients with normal brain MRI, heralding the more typical MOG Ab-associated demyelinating syndrome by days to months. Along clinical phenotyping, we also analysed antibody testing accuracy by comparing different types of cell-based assays (CBAs), coming up to the conclusion that live-CBAs are more accurate than fixed-CBAs, and that live-CBA IgG1 subclasses show the highest specificity, influencing the way in which we now perform screening and confirmatory tests for patients with suspected MOGAD. Finally, we provided evidence that serial longitudinal determination of MOG-IgG titers is a useful prognostic tool in children with MOGAD, as it might predict the risk of relapse and guide clinicians into the most appropriate treatment strategies (i.e. immunosuppressive drugs). The way for the unravelling of this pathology is still long, but we feel that major progresses have been done in the last decade. It is now clear that MOGAD is a distinct entity among aquired demyelinating syndromes, with peculiar (yet heterogeneous) clinical features, relapsing course in a minority of patients and treatment options that differ from those of multiple sclerosis. Long term prognosis is still mainly influenced by the severity of single attacks and possibly by the relapse rate, in both children and adults, and immunomodulatory therapies are currently under study. Future studies will confirm whether relapsing MOGAD is a lifelong illness and will better clarify the long-term morbidity, including the impact on cognition and quality of life.

The clinical spectrum of Myelin Oligodendrocyte Glycoprotein (MOG)-associated disorders in children

FOIADELLI, THOMAS
2020-12-15T00:00:00+01:00

Abstract

Myelin Oligodendrocyte Glycoprotein (MOG) antibody-related disorders (MOGAD) characterize clinically heterogeneous autoimmune diseases affecting the central nervous system (CNS) such as acute disseminated encephalomyelitis (ADEM), recurrent optic neuritis, transverse myelitis and neuromyelitis optica spectrum disorder (NMOSD). Estimated incidence in children is higher than in adults, around 0.3/100,000. Our Paediatrics-Neuroimmunology group have dealt with many pediatric patients with MOG antibody-associated demyelination over the last years. To gain better knowledge over the clinical course, best management and prognostic factors of this intriguing and rare disorder, we established a regional and national network to for data sharing, clinical confrontation and scientific dissemination. We focused on various clinical and laboratory aspects of MOGAD in children, though different multicentre Italian studies. We confirmed, as already reported in the most recent literature, that the clinical onset of MOGAD in children is usually ADEM, followed by ON (typically bilateral), while NMOSD features are more common in adolescents and adults. Similarly, oligoclonal bands are rare in MOGAD and progression to multiple sclerosis is exceptional. Nonetheless, a significant proportion of children with MOGAD experience clinical relapses, and these relapses are more common when MOG-antibody titers persist over time (after 3 to 6 months from the onset), regardless of the acute immunomodulatory treatment. We further recognized the main characteristics of MOG-associated optic neuritis, which are strongly associated with optic disc swelling and increased RFNL, and tend to recover better compared to seronegative optic neuritis. Starting from clinical experience and going through the international scientific literature, we managed to define seizures as an underreported phenotype of MOGAD: in particular, seizures occurred mostly in the context of a cortical encephalitis, or even presented as an isolated phenomenon in patients with normal brain MRI, heralding the more typical MOG Ab-associated demyelinating syndrome by days to months. Along clinical phenotyping, we also analysed antibody testing accuracy by comparing different types of cell-based assays (CBAs), coming up to the conclusion that live-CBAs are more accurate than fixed-CBAs, and that live-CBA IgG1 subclasses show the highest specificity, influencing the way in which we now perform screening and confirmatory tests for patients with suspected MOGAD. Finally, we provided evidence that serial longitudinal determination of MOG-IgG titers is a useful prognostic tool in children with MOGAD, as it might predict the risk of relapse and guide clinicians into the most appropriate treatment strategies (i.e. immunosuppressive drugs). The way for the unravelling of this pathology is still long, but we feel that major progresses have been done in the last decade. It is now clear that MOGAD is a distinct entity among aquired demyelinating syndromes, with peculiar (yet heterogeneous) clinical features, relapsing course in a minority of patients and treatment options that differ from those of multiple sclerosis. Long term prognosis is still mainly influenced by the severity of single attacks and possibly by the relapse rate, in both children and adults, and immunomodulatory therapies are currently under study. Future studies will confirm whether relapsing MOGAD is a lifelong illness and will better clarify the long-term morbidity, including the impact on cognition and quality of life.
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Descrizione: The clinical spectrum of Myelin Oligodendrocyte Glycoprotein (MOG)-associated disorders in children
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11571/1371674
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