Early predictors of disability of paediatric-onset AQP4-IgG-seropositive neuromyelitis optica spectrum disorders

Abstract

ObjectiveTo describe onset clinical features predicting time to first relapse and time to long-term visual, motor and cognitive disabilities in paediatric-onset aquaporin-4 antibody (AQP4-IgG) neuromyelitis optica spectrum disorders (NMOSDs).MethodsIn this retrospective UK multicentre cohort study, we recorded clinical data of paediatric-onset AQP4-IgG NMOSD. Univariate and exploratory multivariable Cox proportional hazard models were used to identify long-term predictors of permanent visual disability, Expanded Disability Status Scale (EDSS) score of 4 and cognitive impairment.ResultsWe included 49 paediatric-onset AQP4-IgG patients (38.8% white, 34.7% black, 20.4% Asians and 6.1% mixed), mean onset age of 12±4.1 years, and 87.7% were female. Multifocal onset presentation occurred in 26.5% of patients, and optic nerve (47%), area postrema/brainstem (48.9%) and encephalon (28.6%) were the most involved areas. Overall, 52.3% of children had their first relapse within 1 year from disease onset. Children with onset age <12 years were more likely to have an earlier first relapse (p=0.030), despite showing no difference in time to immunosuppression compared with those aged 12–18 years at onset. At the cohort median disease duration of 79 months, 34.3% had developed permanent visual disability, 20.7% EDSS score 4 and 25.8% cognitive impairment. Visual disability was associated with white race (p=0.032) and optic neuritis presentations (p=0.002). Cognitive impairment was predicted by cerebral syndrome presentations (p=0.048), particularly if resistant to steroids (p=0.034).ConclusionsAge at onset, race, onset symptoms and resistance to acute therapy at onset attack predict first relapse and long-term disabilities. The recognition of these predictors may help to power future paediatric clinical trials and to direct early therapeutic decisions in AQP4-IgG NMOSD.

Sex bias in multiple sclerosis and neuromyelitis optica spectrum disorders: How it influences clinical course, MRI parameters and prognosis

“…The female predominance in NMOSD occurring in children and adolescents is seen at the ratio of 1.5:1 and 3.25:1 respectively ( 55 ). The other study has shown a 5:1 F:M ratio of AQP4-antibody seropositive patients younger than 12 years ( 56 ). This being said, elderly individuals are also at risk of developing NMOSD.…”

Chronic Cognitive Impairment in AQP4+ NMOSD With Improvement in Cognition on Eculizumab: A Report of Two Cases

“…Cognitive and psychiatric presentations of NMOSD may lead to permanent disability due to delayed recognition and misdiagnosis. Common localization for cognitive and psychiatric relapses in AQP4+ NMOSD have included lesions in the cerebral hemispheres (4), diencephalon (5), and corpus callosum (7), and both of our cases demonstrated prominent involvement of the latter. There have been reported cases of autoimmune encephalitis, in particular NMDA receptor antibody positive encephalitis, co-existing with AQP4+ NMOSD (8,9).…”

Myelitis features and outcomes in CNS demyelinating disorders: Comparison between multiple sclerosis, MOGAD, and AQP4-IgG-positive NMOSD

“…Similarly to MS, the degree of recovery from AQP4+NMOSD attacks is influenced by age and attack severity, with better recovery observed in younger individuals with lower deficits at nadir ( 26 , 78 – 80 ). In a retrospective study on 182 subjects with AQP4+NMOSD, the length of the longest spinal cord lesion measured on MRI was found to be a predictor of more severe residual disability ( 81 ), while another study showed that CSF levels of glial fibrillary acidic protein during acute attacks correlated with the length of spinal cord lesions and with the EDSS at 6 months from the index attack ( 82 ).…”