DeSena AD, Greenberg BM, Graves D
BACKGROUND: Anti-N-methyl-d-aspartate (NMDA) receptor antibody encephalitis is becoming an increasingly recognized cause of encephalopathy in individuals previously presumed to have viral encephalitis. Various manifestations of this disease include altered mental status, behavioral changes, seizures, and movement disorders. We have noted three distinct subtypes of this disease which appear to have differential responses to immunotherapies and differences in prognosis.
METHODS AND PATIENTS: We report eight patients observed at our children’s hospital from 2009 through 2013 who appear to clearly fall into one of our three clinical categories. To find comparable articles reflecting this classification, we then performed a MEDLINE search of all articles involving the subject heading “anti-NMDA receptor encephalitis” or just the keyword phrase “NMDA encephalitis,” and we found 162 articles to review. Twenty-two articles were eliminated due to basic science, and we were able to review 105 of the remaining articles, most of which were case reports or case series, although a few were larger reviews. For the sake of our review, we defined type 1 or “classic” anti-NMDA receptor antibody encephalitis as having a duration of <60 days and being characterized predominantly by a catatonic or stuporous state, type 2 or psychiatric-predominant anti-NMDA receptor antibody encephalitis as having no noteworthy catatonic or stuporous state in addition to the presence of predominantly behavioral and psychiatric symptoms, and type 3 or catatonia-predominant anti-NMDA receptor antibody encephalitis as having a duration of ≥60 days in a predominantly catatonic or stuporous state.
RESULTS: We note that the poorest responders, even to aggressive immunotherapies, are the patients with catatonia-persistent type anti-NMDA receptor antibody encephalitis, which has, as its hallmark, prolonged periods of severe encephalopathy. Patients with predominantly psychiatric symptoms, which we call the psychiatric-predominant anti-NMDA receptor antibody encephalitis, have had excellent responses to plasma exchange or other immunotherapies and appear to have the least residual deficits at follow-up. Patients with fairly equal representations of periods of altered mental status, behavioral problems, and movement disorders appear to have an intermediate prognosis and likely require early aggressive immunotherapy.
CONCLUSIONS: In our series, we discuss representative examples of these clinical subtypes and their associated outcomes, and we suggest that tracking these subtypes in future cases of anti-NMDA receptor antibody encephalitis might lead to better understanding and better risk stratification with regard to immunotherapy decisions.
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DeSena AD, Greenberg BM, Graves D
BACKGROUND: Anti-N-methyl-D-aspartate antibody encephalitis is becoming increasingly recognized as a cause of acute and subacute encephalopathy in both adults and children. The typical features of this disorder include some degree of encephalopathy, seizures, and often a movement disorder component. However, there is wide variability in its presentation, and diagnosis based on clinical features alone is often delayed.
PATIENTS: We report a series of four of 12 patients observed at our children’s hospital between 2011 and 2013 that we chose as particularly representative examples of two distinct clinical features.
RESULTS: In these individuals with anti-N-methyl-D-aspartate receptor antibody encephalitis, we note a very rapid on-off state between responsiveness and nonresponsiveness and/or insomnia accompanied by extreme irritability. We describe the abrupt mental status shift as “light switch” because the patients can awaken in seconds from a completely nonresponsive state. The insomnia noted in our patients was also impressive and often present early in the patients’ courses.
CONCLUSIONS: Light switch mental status changes and irritable insomnia are important early features of anti-N-methyl-D-aspartate receptor antibody encephalitis that can signal the presence of this disorder. The exact pathophysiology of these two symptoms has not been fully elucidated, and we feel that presence of one or both of these symptoms early in the disease course should prompt immediate concern for this disorder.