Early blood neurofilament light chain and myelin oligodendrocyte glycoprotein antibody levels associate with different disease courses of myelin oligodendrocyte glycoprotein-associated disease in children.

Acquired demyelinating syndrome associated with myelin oligodendrocyte glycoprotein antibodies, named recently myelin oligodendrocyte glycoprotein-associated disease, represents >27% of this paediatric syndrome. Relapses occur in 40% of them, which may be associated with severe outcomes. Aiming to identify biomarker allowing to predict relapse, we measured both myelin oligodendrocyte glycoprotein antibodies and neurofilament light chain levels in blood samples of patients that are known to reflect axonal injuries in neurological diseases including demyelinating autoimmune disorders. Three groups of patients were selected: relapsing myelin oligodendrocyte glycoprotein-associated disease (n = 8), non-relapsing myelin oligodendrocyte glycoprotein-associated disease (n = 7) and control patients with non-inflammatory neurological diseases (n = 12). Neurofilament light chain concentrations were measured in plasma of these three groups of patients using the high-sensitivity single-molecule array method at onset of the disease and 6 months later. At onset of the disease, we found that levels of neurofilament light chain in blood of non-relapsing patients were significantly higher than in control patients (means: 98.36 ± 22.66 versus 12.47 ± 2.47 pg/mL, **P < 0.01, Kruskal-Wallis test). The mean neurofilament light chain value in relapsing patients (82.16 ± 38.41 pg/mL) was not significantly different from that in non-relapsing and in control patients. Plasma myelin oligodendrocyte glycoprotein antibody levels were 2.5-fold higher in relapsing than in non-relapsing patients without reaching significance (means: 15.26 ± 4.87 versus 5.96 ± 1.13; two-tailed Mann-Whitney U-test P = 0.119). Plasma neurofilament light chain correlated significantly with myelin oligodendrocyte glycoprotein antibody levels in relapsing (two-tailed Spearman r = 0.8, P = 0.0218) but not in non-relapsing (two-tailed Spearman r = 0.17, P = 0.71). Interestingly, the ratio of neurofilament light chain-to-myelin oligodendrocyte glycoprotein antibodies was significantly lower in relapsing than in non-relapsing patients (means: 5.19 ± 1.61 versus 21.87 ± 6.13; two-tailed Mann-Whitney U-test P = 0.014). These findings suggest that measuring both neurofilament light chain and myelin oligodendrocyte glycoprotein antibody levels in patients at onset of demyelinating disease could predict relapse of myelin oligodendrocyte glycoprotein-associated disease.

Long-term outcome of paediatric anti-N-methyl-D-aspartate receptor encephalitis.

AIM: To study long-term clinical and cognitive outcomes of patients with anti-N-methyl-d-aspartate receptor encephalitis (NMDAR-E), an acute autoimmune neurological disease with severe acute presentations. METHOD: In this French multicentre retrospective observational cohort study, patients no older than 18 years with a follow-up of at least 2 years were included. Data from clinical and cognitive assessments were collected. RESULTS: Eighty-one patients were included (57 females, 24 males; median age 10 years 7 months [range 1-18 years], median follow-up 40 months [range 25-53 months]). At last follow-up, 35 patients (45%) had cognitive impairment, 48 (70%) had academic difficulties, and 65 (92%) needed rehabilitation. Seventy-one patients (88%) had a modified Rankin Scale score of no more than 2. A higher number of symptoms at diagnosis was associated with cognitive impairment (p = 0.01), while an abnormal electroencephalogram at diagnosis increased the risk of academic difficulties (p = 0.03). INTERPRETATION: Although most children with NMDAR-E seemed to recover from motor disabilities, more than 45% had cognitive and academic difficulties. The initial severity of symptoms seems to have an impact on cognition and academic performances. WHAT THIS PAPER ADDS: Forty-five per cent of patients had cognitive impairment at ≥2 years diagnosis of anti-N-methyl-d-aspartate receptor encephalitis (NMDAR-E). Seventy per cent of patients had academic difficulties at ≥2 years diagnosis of NMDAR-E. Ninety-two per cent of patients needed rehabilitative care at ≥2 years diagnosis of NMDAR-E. A high number of symptoms at diagnosis were associated with cognitive impairment.

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

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 5 - Treatment of paediatric myelin oligodendrocyte glycoprotein antibody-associated disorders.

In recent years, the understanding about the different clinical phenotypes, diagnostic and prognostic factors of myelin oligodendrocyte glycoprotein-antibody-associated disorders (MOGAD) has significantly increased. However, there is still lack of evidence-based treatment protocols for acute attacks and children with a relapsing course of the disease. Currently used acute and maintenance treatment regimens are derived from other demyelinating central nervous system diseases and are mostly centre-specific. Therefore, this part of the Paediatric European Collaborative Consensus attempts to provide recommendations for acute and maintenance therapy based on clinical experience and evidence available from mainly retrospective studies. In the acute attack, intravenous methylprednisolone (IVMP) leads to a favourable outcome in the majority of patients and can be followed by tapering of oral steroids up to a maximum of three months to maintain the benefit of acute treatment by suppressing disease activity. Intravenous immunoglobulins (IVIG) and plasmapheresis constitute second-line therapies in case of insufficient response to IVMP. After a first relapse, maintenance treatment should be started in order to prevent further relapses and the possibility of permanent sequelae. Four first-line therapies consisting of rituximab (RTX), azathioprine, mycophenolate mofetil or monthly IVIG have been identified by the consensus group. In case of further relapses despite maintenance treatment, the consensus group recommends treatment escalation with RTX or IVIG, followed by combining those two, and ultimately adding maintenance oral steroids. Many open questions remain which need to be addressed in further international prospective evaluation of MOGAD treatment. This international collaboration is essential to expand the state of current knowledge.