Ann Neurol. Author manuscript; available in PMC 2010 February 22.
Published in final edited form as:
Ann Neurol. 2009 July; 66(1): 11?18.
doi: 10.1002/ana.21756.
PMCID: PMC2826225
NIHMSID: NIHMS173684
Anti?N-Methyl-D-Aspartate Receptor (NMDAR) Encephalitis in Children and Adolescents
Nicole R. Florance, MD,1 Rebecca L. Davis, BA,2 Christopher Lam, MD,3 Christina Szperka, MD,1 Lei Zhou, BS,2 Saba Ahmad, MD,1 Cynthia J. Campen, MD,1 Heather Moss, MD, PhD,2 Nadja Peter, MD,4 Amy J. Gleichman, BS,5 Carol A. Glaser, MD,6 David R. Lynch, MD, PhD,1,2 Myrna R. Rosenfeld, MD, PhD,2 and Josep Dalmau, MD, PhD2
1Division of Neurology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA
2Department of Neurology, University of Pennsylvania, Philadelphia, PA
3Division of Psychiatry, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA
4Division of Adolescent Medicine, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA
5Department of Neuroscience, School of Medicine, University of Pennsylvania, Philadelphia, PA
6Viral and Rickettsial Disease Laboratory, Division of Communicable Disease Control, Center of Infectious Disease, California Department of Public Health, Richmond, CA
Objective
To report the clinical features of anti?N-methyl-D-aspartate receptor (NMDAR) encephalitis in patients ≤ 18 years old.
Methods
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.
Results
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).
Interpretation
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.
