Severe childhood encephalopathy with dyskinesia and prolonged cognitive disturbances: evidence for anti-N-methyl-D-aspartate receptor encephalitis.
OBJECTIVE
We report four cases of acquired severe encephalopathy with massive hyperkinesia, marked neurological and cognitive regression, sleep disturbance, prolonged mutism, and a remarkably delayed recovery (time to full recovery between 5 and 18mo) with an overall good outcome, and its association with anti-N-methyl-d-aspartate (anti-NMDA) receptor antibodies.


METHODS
We reviewed the four cases retrospectively and we also reviewed the literature.


RESULTS
Anti-NMDA receptor antibodies (without ovarian teratoma detected so far) were found in the two children tested in this study.


CONCLUSIONS
The clinical features are similar to those first reported in 1992 by Sebire et al.,(1) and rarely recognized since. Sleep disturbance was not emphasized as part of the disorder, but appears to be an important feature, whereas coma is less certain and difficult to evaluate in this setting. The combination of symptoms, evolution (mainly seizures at onset), severity, paucity of abnormal laboratory findings, very slow recovery, and difficult management justify its recognition as a specific entity. The neuropathological substrate may be anatomically close to that involved in encephalitis lethargica, in which the same target functions (sleep and movement) are affected but in reverse, with hypersomnolence and bradykinesia. This syndrome closely resembles anti-NMDA receptor encephalitis, which has been reported in adults and is often paraneoplastic.
Poloni
Claudia
C
Department of Paediatrics, Child Neurology, University Hospital Lausanne, Lausanne, Switzerland.
Korff
Christian M
CM
Ricotti
Valeria
V
King
Mary D
MD
Perez
Eliane Roulet
ER
Mayor-Dubois
Claire
C
Haenggeli
Charles-Antoine
CA
Deonna
Thierry
T
D001323:Autoantibodies / Q000097:blood; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D003072:Cognition Disorders / Q000209:etiology* / Q000503:physiopathology; D020820:Dyskinesias / Q000209:etiology* / Q000503:physiopathology; D004569:Electroencephalography; D004660:Encephalitis / Q000150:complications* / Q000175:diagnosis / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D009155:Mutism / Q000209:etiology; D011379:Prognosis; D016194:Receptors, N-Methyl-D-Aspartate / Q000276:immunology*; D012189:Retrospective Studies; D012720:Severity of Illness Index; D012893:Sleep Wake Disorders / Q000209:etiology* / Q000503:physiopathology; D013997:Time Factors
D001323:Autoantibodies; D016194:Receptors, N-Methyl-D-Aspartate