N-methyl-D-aspartate receptor antibody-mediated neurological disease: results of a UK-based surveillance study in children

Abstract

Objective: N-methyl-D-aspartate receptor antibody (NMDAR-Ab) encephalitis is a well-recognised clinico-immunological syndrome that presents with neuropsychiatric symptoms cognitive decline, movement disorder and seizures. This study reports the clinical features, management and neurological outcomes of paediatric NMDAR-Ab-mediated neurological disease in the UK.

Design: A prospective surveillance study. Children with NMDAR-Ab-mediated neurological diseases were voluntarily reported to the British Neurological Surveillance Unit (BPNSU) from November 2010 to December 2011. Initial and follow-up questionnaires were sent out to physicians.

Results: Thirty-one children fulfilled the criteria for the study. Eight presented during the study period giving an incidence of 0.85 per million children per year (95% CI 0.64 to 1.06); 23 cases were historical. Behavioural change and neuropsychiatric features were present in 90% of patients, and seizures and movement disorders both in 67%. Typical NMDAR-Ab encephalitis was reported in 24 children and partial phenotype without encephalopathy in seven, including predominantly psychiatric (four) and movement disorder (three). All patients received steroids, 22 (71%) received intravenous immunoglobulin, 9 (29%) received plasma exchange,and 10 (32%) received second-line immunotherapy. Of the 23 patients who were diagnosed early, 18 (78%) made a full recovery compared with only 1 of 8 (13%) of the late diagnosed patients (p=0.002, Fisher's exact test). Seven patients relapsed, with four needing additional second-line immunotherapy.

Conclusions: Paediatric NMDAR-Ab-mediated neurological disease appears to be similar to adult NMDAR-Ab encephalitis, but some presented with a partial phenotype. Early treatment was associated with a quick and often full recovery.

Keywords: Autoantibody; Encephalitis; NMDA receptors; Neurology; immunotherapy.

Figure 1

Demographic data of UK patients with N-methyl-D-aspartate receptor-antibody encephalitis. Age of onset stratified to sex (A) showing an overall female predominance. Boys were more likely to present at over the age of 5 years (p=0.03, Fisher's exact test). Ethnicity of the patients (B), 14 patients (45%) were non-Caucasian.

Figure 2

(A) Pie chart showing the four treatment groups of the whole cohort. Group A had intravenous immunoglobulin and oral/ intravenous steroids only (first-line) and no plasma exchange (PLEX); Group B had first-line immunotherapy and plasma exchange; Group C had first-line immunotherapy, no PLEX and second-line immunotherapy; Group D had all the treatments (first-line, PLEX and second-line immunotherapy). (B) Graph to show the late diagnosed patient group continues to make progress over time despite no aggressive or long-term treatment. (C) Table summarises outcomes showing that all patients diagnosed early make a full/partial recovery (p=0.0011**, χ² for trend).

Figure 3

Bar chart to show number and range of allied health professionals and other medical specialities required in the management of N-methyl-D-aspartate receptor-antibody neurological disease in paediatric patients in the UK.