Potential conflict of interest: Nothing to report.
Anti–N-methyl-D-aspartate receptor (NMDAR) encephalitis in children and adolescents†
Article first published online: 28 MAY 2009
Copyright © 2009 American Neurological Association
Annals of Neurology
Volume 66, Issue 1, pages 11–18, July 2009
How to Cite
Florance, N. R., Davis, R. L., Lam, C., Szperka, C., Zhou, L., Ahmad, S., Campen, C. J., Moss, H., Peter, N., Gleichman, A. J., Glaser, C. A., Lynch, D. R., Rosenfeld, M. R. and Dalmau, J. (2009), Anti–N-methyl-D-aspartate receptor (NMDAR) encephalitis in children and adolescents. Ann Neurol., 66: 11–18. doi: 10.1002/ana.21756
- Issue published online: 10 AUG 2009
- Article first published online: 28 MAY 2009
- Accepted manuscript online: 28 MAY 2009 12:00AM EST
- Manuscript Accepted: 18 MAY 2009
- Manuscript Revised: 10 MAY 2009
- Manuscript Received: 25 FEB 2009
- National Cancer Institute
- National Institute of Health. Grant Numbers: 2RO1CA89054, RO1CA107192, NSR56-45986, NSR01-45986
- Foederer Foundation of the Children's Hospital of Philadelphia
- National Institute of Mental Health (NIMH). Grant Number: F31MH083395
To report the clinical features of anti–N-methyl-D-aspartate receptor (NMDAR) encephalitis in patients ≤ 18 years old.
Information was obtained by the authors or referring physicians. Antibodies were determined by immunocytochemistry and enzyme-linked immunosorbent assay (ELISA) using HEK293 cells ectopically expressing NR1.
Over an 8-month period, 81 patients (12 male) with anti-NMDAR encephalitis were identified. Thirty-two (40%) were ≤18 years old (youngest 23 months, median 14 years); 6 were male. The frequency of ovarian teratomas was 56% in women >18 years old, 31% in girls ≤18 years old (p = 0.05), and 9% in girls ≤14 years old (p = 0.008). None of the male patients had tumors. Of 32 patients ≤18 years old, 87.5% presented with behavioral or personality change, sometimes associated with seizures and frequent sleep dysfunction; 9.5% with dyskinesias or dystonia; and 3% with speech reduction. On admission, 53% had severe speech deficits. Eventually, 77% developed seizures, 84% stereotyped movements, 86% autonomic instability, and 23% hypoventilation. Responses to immunotherapy were slow and variable. Overall, 74% had full or substantial recovery after immunotherapy or tumor removal. Neurological relapses occurred in 25%. At the last follow-up, full recovery occurred more frequently in patients who had a teratoma that was removed (5/8) than in those without a teratoma (4/23; p = 0.03).
Anti-NMDAR encephalitis is increasingly recognized in children, comprising 40% of all cases. Younger patients are less likely to have tumors. Behavioral and speech problems, seizures, and abnormal movements are common early symptoms. The phenotype resembles that of the adults, although dysautonomia and hypoventilation are less frequent or severe in children. Ann Neurol 2009;66:11–18