A systematic review and quantitative synthesis of the long-term psychiatric sequelae of pediatric autoimmune encephalitis

J Affect Disord. 2022 Jul 1:308:449-457. doi: 10.1016/j.jad.2022.04.027. Epub 2022 Apr 13.


Background: Long-term neuropsychiatric sequelae of autoimmune encephalitis (AE) remain understudied, particularly in pediatric-onset AE. We aimed to synthesize the published data on ongoing psychiatric symptoms in pediatric-onset AE.

Methods: The Pubmed, PyscINFO, Web of Science databases were searched from their inception years to August 23, 2021, and 29 studies were identified and analyzed. We also performed a quantitative synthesis of available patient data from the 29 studies combined with a cohort of anti-NMDA receptor (NMDAR) AE from our institution to examine the associations between acute treatment course and long-term psychiatric outcome.

Results: At long-term follow up, 52.4% of the cases with pediatric-onset AE had any persistent symptom and 36.0% had at least one psychiatric symptom. Pooled data found that 36.3% of pediatric-onset anti-NMDAR AE had ongoing psychiatric symptoms. Using a univariate logistic regression analysis, we found that abnormal initial EEG, use of certain immunotherapies, and persistent cognitive impairments were associated with ongoing psychiatric symptoms.

Limitations: Limitations of the existing literature included a significant paucity of outcomes measured using consistent, objective methods. Limitations of the systematic review included the wide variability among the studies reviewed, which rendered a meta-analysis impossible and beyond the scope of the paper.

Conclusion: Chronic psychiatric and behavioral problems remain present in one-third of children months to years after onset of AE. Larger scaled prospective observational studies with a consistent standardized battery of testing are needed to examine impact of specific clinical features and immunotherapies on long-term mental health outcomes.

Keywords: Anti-NMDA receptor encephalitis; Autoimmune encephalitis; Long term sequelae; Pediatric onset; Psychiatric outcomes.

Publication types

  • Systematic Review

MeSH terms

  • Anti-N-Methyl-D-Aspartate Receptor Encephalitis* / complications
  • Anti-N-Methyl-D-Aspartate Receptor Encephalitis* / diagnosis
  • Anti-N-Methyl-D-Aspartate Receptor Encephalitis* / therapy
  • Child
  • Disease Progression
  • Encephalitis
  • Hashimoto Disease* / complications
  • Humans
  • Mental Disorders* / therapy
  • Observational Studies as Topic

Supplementary concepts

  • Hashimoto's encephalitis