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Home » Anti-NMDA Receptor Encephalitis or New-Onset Psychosis?

Anti-NMDA Receptor Encephalitis or New-Onset Psychosis?

July 14, 2021
Alex Thompson, MD.
From The Carlat Hospital Psychiatry Report
Issue Links: Learning Objectives | Editorial Information | PDF of Issue
Alex Thompson, MD. Dr. Thompson has disclosed no relevant financial or other interests in any commercial companies pertaining to this educational activity.
Review of: Xu X et al, Neurol Neuroimmunol Neuroinflamm 2019;7(1):e633

You may have heard of the book Brain on Fire: My Month of Madness by Susannah Cahalan (later made into a movie). Cahalan, a successful journalist, describes her brief psychotic episode that led to hospitalizations and mistaken psychiatric diagnoses. She was eventually diagnosed with anti-NMDA receptor encephalitis, in which the body produces antibodies to NMDA receptors, causing a variety of psychiatric and neurological symptoms. The diagnosis requires detecting the antibodies in the cerebrospinal fluid (CSF).

Anti-NMDA receptor encephalitis typically presents in younger women (many of whom have an ovarian teratoma), and early identification and treatment is key to prevent substantial morbidity or death. To halt ongoing brain injury, the standard of care is immunosuppression treatment in the form of steroids, plasmapheresis, intravenous immunoglobulin (IVIG), monoclonal antibodies (rituximab), and cyclophosphamide.

To help develop better treatment guidelines, Chinese investigators published a 12-month observational study of 220 patients with anti-NMDA receptor encephalitis. The goal was to better characterize the presentation, clinical course, and outcome of the disease. Long-term outcomes were measured using the modified Rankin Scale (mRS), a 6-point scale (0 = no disability, 5 = severe disability) used to assess disability outcomes in patients who have had strokes.

The findings affirm what we know about anti-NMDA receptor encephalitis: 65% of patients were female (of which 30% had teratomas), the median age was 21 years old, and only 36% had abnormal MRI findings on presentation. At initial presentation, 83% had psychosis, 81% had seizures, and 51% had abnormal EEG findings. While 100% had CSF antibodies to NMDA receptors, only 71% had serum antibodies, meaning blood work alone cannot rule out the disease.

The outcomes give us hope: While the median disability score at onset was 4 (moderately severe disability), at 12 months, 93% of the cohort had no more than a slight disability, with over 60% showing no symptoms. Overall, the median time from diagnosis to treatment was 2 weeks.

CHPR’s Take
While uncommon (the incidence is 1.5 per million people per year), anti-NMDA receptor encephalitis should be on our psychosis differential, especially for younger women with new-onset psychosis who have a history of a viral prodrome and subtle neurologic abnormalities. In such patients, you should have a low threshold for consulting neurology, and for ordering neuroimaging, EEG testing, and CSF analysis.
Hospital Psychiatry
KEYWORDS anti-nmda-receptor-encephalitis encephalitis female-issues-in-psychiatry nmda psychosis womens-issues-in-psychiatry
    Alex Thompson, MD.

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    Issue Date: July 14, 2021
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