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

J Neurol Neurosurg Psychiatry. 2022 Jan;93(1):101-111. doi: 10.1136/jnnp-2021-327206. Epub 2021 Sep 28.

Abstract

Objective: To 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).

Methods: In 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.

Results: We 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).

Conclusions: Age 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.

Keywords: paediatric neurology.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Antibodies / blood
  • Aquaporin 4*
  • Asian People / statistics & numerical data
  • Black People / statistics & numerical data
  • Brain / pathology
  • Child
  • Cohort Studies
  • Disability Evaluation
  • Disabled Persons / statistics & numerical data*
  • Disease Progression
  • Female
  • Humans
  • Immunoglobulin G / therapeutic use
  • Male
  • Middle Aged
  • Neuromyelitis Optica / diagnosis*
  • Optic Nerve / pathology
  • Proportional Hazards Models
  • Retrospective Studies
  • United Kingdom
  • White People / statistics & numerical data
  • Young Adult

Substances

  • Antibodies
  • Aquaporin 4
  • Immunoglobulin G