ABSTRACT Introduction. Almost one third of all acute demyelinating syndromes (ADS) in children are associated with myelin oligodendrocyte glycoprotein (MOG) antibodies (Abs). MOG Abs-related encephalomyelitis (MOG-EM) is a relatively “new” and clinically heterogeneous ADS, which has distinctive clinical and prognostic features compared to multiple sclerosis and aquaporin-4-positive neuromyelitis optica (NMO). Objective. Our aim was to characterize the clinical and radiological factors of MOG-EM in a cohort of children with MOG-EM, and the prognostic role of serum MOG Abs titers at onset and during follow-up. Analysis of such factors is crucial for the understanding of the physiopathological mechanisms of this disease and to target future therapeutic and preventive strategies. Materials and methods. We conducted a multicenter retrospective observational study. Sixteen children (< 18 years) fulfilling inclusion criteria for MOG-EM were included. The immunological investigations of anti MOG titer have been carried through live Cell Based Assay (CBA) in the Neuroimmunology Laboratory of the Neurological Institute “C. Mondino” (Pavia). Results. The first demyelinating event was classified as ADEM in nine patients (56,3 %), isolated optic neuritis in four (25%), clinically isolated syndrome in two (12,5%), and neuromyelitis optica spectrum disorder in one (6,2%). Oligoclonal bands were present in 3/13 (23,1%), pleocytosis in 2/13 (15,4%). Brain MRI showed white matter alterations in 12/14 (85,7%) patients, brainstem alterations in 5/14 (35,7%), anomalies at the area postrema in 2/14 (14,3%) and it showed no demyelinating lesions in 2/14 (14,3%) patients. Optic nerves were involved bilaterally in 4/10 (40%), and unilaterally in 1/10 (10%). Only 2/11 (18,2%) had spinal lesions: one with a longitudinally extended transverse myelitis, and one with an isolated spinal hyperintensity in the cervical tract. All the EEG, whenever performed, showed abnormally slow background activity. The visual evoked potential were pathological in 6/10 patients (60%). Six children (37,5%) relapsed (mean follow up: 24 months). Final diagnosis was monophasic ADEM in 5/16 patients (31,3%), optic neuritis in 4/16 (25%), multiphasic ADEM in 2/16 (12,5%), CIS in 2/16 (12,5%), MS in 1/16 (6,3%), NMOSD in 1/16 (6,3%), and “non specified encephalomyelitis” in 1/16 (6,3%). Six out of 16 patients (37,5%) developed neurological sequelae. Liquor and/or serum MOG Abs were detected in all children. 11/16 patients (68,8%) had serial determination of ≥2 MOG Abs titers. Two patients (18,8%) showed a negativity of the anti MOG titer after steroid therapy, both completely recovered and did not relapse. Persistence of MOG Abs titers was present in 9/11 patients (81,8%) and five of them (55,6%) had a relapsing course. All the patients were started with steroids. Immunoglobulins were given in 3/16 patients (18,8%). Azathioprine was started in 2/16 patients (12,5%), Rituximab in 1/16 (6,3%). The type of acute treatment (steroids or IVIG) did not affect the probability of negativization of the MOG Abs at follow up, although starting an immunosuppressive treatment as soon as possible is crucial for the prognosis. Conclusions. Early identification of MOG Abs in a child with ADS is critical for a correct diagnosis and management, and for prognostic reasons. In fact, MOG Abs are not correlated with an evolution to MS, but their persistence after an acute demyelinating event can possibly predict future relapses. Early diagnosis for these pathologies to start an adequate immunosuppressive treatment as soon as possible and, in selected cases, to undergo long-term immunomodulatory therapies to avoid long-term sequalae and prevent disease relapses.
Introduzione. Quasi un terzo di tutte le acute demyelinating syndromes (ADS) in età pediatrica è associato alla positività ad anticorpi (Abs) contro la glicoproteina oligodendrocita della mielina (MOG). L'encefalomielite anti-MOG (MOG-EM) è una ADS relativamente "nuova" e clinicamente eterogenea, che presenta caratteristiche cliniche e prognostiche distinte rispetto alla sclerosi multipla e alla neuromielite ottica (NMO) acquaporina-4 positiva. Obiettivo. Lo scopo di questo studio è di caratterizzare i fattori clinici e radiologici in una coorte di bambini con MOG-EM ed analizzare il ruolo prognostico dei titoli sierici di MOG Abs all'esordio e nel corso del follow-up. L'analisi di tali fattori è cruciale per la comprensione dei meccanismi fisiopatologici di questa malattia e per indirizzare future strategie terapeutiche e preventive. Materiali e metodi. Si tratta del primo studio retrospettivo osservazionale multicentrico italiano. Abbiamo arruolato sedici bambini e adolescenti (<18anni) con MOG-EM. Le indagini immunologiche sul titolo anti MOG sono state condotte attraverso “live Cell Based Assay” (CBA) dal Laboratorio di Neuroimmunologia dell'Istituto Neurologico “C. Mondino” (Pavia). Risultati. Il primo evento demielinizzante è stato classificato come ADEM in nove pazienti (56,3%), come neurite ottica isolata in quattro (25%), come clinically isolated syndrome (CIS) (12,5%) e neuromyelitis optica spectrum disorder in uno (6,2%). Le bande oligoclonali erano presenti in 3/13 (23,1%), la pleiocitosi in 2/13 (15,4%), la RM cerebrale mostrava alterazioni della sostanza bianca in 12/14 pazienti (85,7%). La via ottica era bilateralmente patologica in 4/10 (40%). La RM spinale era negativa in 8/11 pazienti (72,7%). Tutti gli EEG erano lenti e il potenziale evocato visivo era patologico in 6/10 pazienti (60%). Sei bambini (37,5%) hanno recidivato (follow-up medio: 24 mesi). La diagnosi finale è stata ADEM monofasica in 5/16 pazienti (31,3%), neurite ottica in 4/16 (25%), ADEM multifasica in 2/16 (12,5%), CIS in 2/16 (12,5%), SM in 1/16 (6,3%), NMOSD in 1/16 (6,3%), encefalomielite non specificata in 1/16 (6,3%). Sei su 16 pazienti (37,5%) hanno sequele neurologiche. I titoli MOG in liquor o siero sono stati rilevati in tutti i bambini, seguendo i criteri di inclusione. Più di un titolo anticorpale era disponibile in 11/16 pazienti (68,8%). Due pazienti (18,8%) hanno mostrato una negatività del titolo anti MOG ed entrambi hanno avuto un completo recupero secondo la mRS e EDSS senza ricadute, ma tale risultato non è statisticamente significativo probabilmente a causa di una popolazione di pazienti pco numerosa. La persistenza dei titoli per più di quattro mesi era presente nei pazienti in 9/11 pazienti (81,8%) e cinque di essi (55,6%) avevano un decorso recidivante. Quattro dei pazienti (80%) con persistenza anti MOG e recidive hanno manifestato ADEM. Una persistenza anti-MOG senza avere un decorso recidivante è stata osservata 4/11 pazienti (36,4%). Tutti i pazienti sono stati trattati in acuto con steroidi, tre pazienti (18,8%). L'azatioprina è stata iniziata da 2/16 pazienti (12,5%), il Rituximab da 1/16 (6,3%). Il tipo di trattamento scelto (steroidi e/o immunoglobuline) non sembra influenzare la negativizzazione degli anticorpi e la prognosi. Conclusioni. L'identificazione precoce di MOG Abs in un bambino con ADS è indispensabile per una corretta diagnosi e gestione e per ragioni prognostiche. Infatti la persistenza di titoli MOG dopo un evento demielinizzante acuto può correlare ad un aumentato rischio di ricadute cliniche. E’ fondamentale una diagnosi precoce di queste patologie per iniziare un adeguato trattamento immunosoppressivo il più presto possibile e, in casi selezionati, sottoporre i pazienti a terapie immunomodulanti a lungo termine per evitare sequele e prevenire le ricadute della malattia.
Clinical-radiologic phenotype and prognostic factors in children with anti MOG encephalomyelitis: an Italian multicenter study
ONORATI, LORENZA ROSANGELA
2019/2020
Abstract
ABSTRACT Introduction. Almost one third of all acute demyelinating syndromes (ADS) in children are associated with myelin oligodendrocyte glycoprotein (MOG) antibodies (Abs). MOG Abs-related encephalomyelitis (MOG-EM) is a relatively “new” and clinically heterogeneous ADS, which has distinctive clinical and prognostic features compared to multiple sclerosis and aquaporin-4-positive neuromyelitis optica (NMO). Objective. Our aim was to characterize the clinical and radiological factors of MOG-EM in a cohort of children with MOG-EM, and the prognostic role of serum MOG Abs titers at onset and during follow-up. Analysis of such factors is crucial for the understanding of the physiopathological mechanisms of this disease and to target future therapeutic and preventive strategies. Materials and methods. We conducted a multicenter retrospective observational study. Sixteen children (< 18 years) fulfilling inclusion criteria for MOG-EM were included. The immunological investigations of anti MOG titer have been carried through live Cell Based Assay (CBA) in the Neuroimmunology Laboratory of the Neurological Institute “C. Mondino” (Pavia). Results. The first demyelinating event was classified as ADEM in nine patients (56,3 %), isolated optic neuritis in four (25%), clinically isolated syndrome in two (12,5%), and neuromyelitis optica spectrum disorder in one (6,2%). Oligoclonal bands were present in 3/13 (23,1%), pleocytosis in 2/13 (15,4%). Brain MRI showed white matter alterations in 12/14 (85,7%) patients, brainstem alterations in 5/14 (35,7%), anomalies at the area postrema in 2/14 (14,3%) and it showed no demyelinating lesions in 2/14 (14,3%) patients. Optic nerves were involved bilaterally in 4/10 (40%), and unilaterally in 1/10 (10%). Only 2/11 (18,2%) had spinal lesions: one with a longitudinally extended transverse myelitis, and one with an isolated spinal hyperintensity in the cervical tract. All the EEG, whenever performed, showed abnormally slow background activity. The visual evoked potential were pathological in 6/10 patients (60%). Six children (37,5%) relapsed (mean follow up: 24 months). Final diagnosis was monophasic ADEM in 5/16 patients (31,3%), optic neuritis in 4/16 (25%), multiphasic ADEM in 2/16 (12,5%), CIS in 2/16 (12,5%), MS in 1/16 (6,3%), NMOSD in 1/16 (6,3%), and “non specified encephalomyelitis” in 1/16 (6,3%). Six out of 16 patients (37,5%) developed neurological sequelae. Liquor and/or serum MOG Abs were detected in all children. 11/16 patients (68,8%) had serial determination of ≥2 MOG Abs titers. Two patients (18,8%) showed a negativity of the anti MOG titer after steroid therapy, both completely recovered and did not relapse. Persistence of MOG Abs titers was present in 9/11 patients (81,8%) and five of them (55,6%) had a relapsing course. All the patients were started with steroids. Immunoglobulins were given in 3/16 patients (18,8%). Azathioprine was started in 2/16 patients (12,5%), Rituximab in 1/16 (6,3%). The type of acute treatment (steroids or IVIG) did not affect the probability of negativization of the MOG Abs at follow up, although starting an immunosuppressive treatment as soon as possible is crucial for the prognosis. Conclusions. Early identification of MOG Abs in a child with ADS is critical for a correct diagnosis and management, and for prognostic reasons. In fact, MOG Abs are not correlated with an evolution to MS, but their persistence after an acute demyelinating event can possibly predict future relapses. Early diagnosis for these pathologies to start an adequate immunosuppressive treatment as soon as possible and, in selected cases, to undergo long-term immunomodulatory therapies to avoid long-term sequalae and prevent disease relapses.È consentito all'utente scaricare e condividere i documenti disponibili a testo pieno in UNITESI UNIPV nel rispetto della licenza Creative Commons del tipo CC BY NC ND.
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https://hdl.handle.net/20.500.14239/11813