Immune- mediated encephalitis is the most common cause of encephalitis after infection in children and adults. Although this disease process was identified nearly 20 years ago, the variety of clinical presentations and the lack of specific diagnostic criteria can make the identification of anti-N-methyl-D-aspartate receptors (NMDA-R) encephalitis challenging. Moreover, identifying NMDA-R antibodies in blood or cerebrospinal fluid can take days to weeks, and thus clinicians need to have a high index of suspicion to investigate for this disease in patients who may appear to have an overlap of neurologic and psychiatric symptomatology. In this article, the authors describe three illustrative cases of anti-NMDA-R encephalitis in children age 3 to 16 years. The discussion reviews our current understanding of the clinical presentation, diagnostic criteria, and inpatient therapeutic management of anti-NMDA-R encephalitis, as well as illuminates the unique and often perplexing presentations of this disease process versus other organic and psychiatric causes of altered mental status. [Pediatr Ann. 2019;48(10):e387-e390.].
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