A Clinician’s Guide to Diagnosing Autoimmune Anti-NDMA Receptor Encephalitis in Psychiatry

Journal of Psychiatry Reform Vol 9 #13, August 2022

Author Information

William B. Provosty1*, Gemma Esepjo2

*Correspondence: [email protected]

1 Resident Physician, Department of Psychiatry and Behavioral Sciences, Montefiore Medical Center 111 E 210 St, Bronx, NY 10467

2 Attending Physician, Department of Psychiatry and Behavioral Sciences, Montefiore Medical Center 111 E 210 St, Bronx, NY 1046

A newly diagnosed psychotic disorder can bring a devastating prognosis. As such, it is important to understand the pathology. Identifying autoimmune etiology can be lifesaving as the recovery rate (80%) is much higher compared to schizophrenia.[1],2 The goal of this paper is to provide physicians with a quick-reference guide to the signs, symptoms and diagnostic findings that raise suspicion for the most extensively studied of these autoimmune causes, anti-N-methyl D-aspartate (NMDA) receptor encephalitis. 1

Obtaining an accurate and thorough history is essential to identifying the cause of psychosis. Retrospective analysis found that in anti-NMDA receptor encephalitis, psychiatric abnormalities are the most common presenting symptom.1 Rapid onset of psychiatric symptoms over the course of days or weeks, female sex (female-to-male ratio, 4:1), or young age (younger than 18 years old) should raise suspicion for autoimmune etiology.3 Other common symptoms include alterations in memory, fever, headache, viral prodrome, decreased levels of consciousness, dysautonomia, and seizures. A full list of symptoms can be found in Table 11,3.

Serum testing has demonstrated limited clinic significance as similar titers of anti-NMDA IgG and IgA have been found in healthy and diseased patients.1,3 Therefore, a suggested cut off for serum titers of anti-NMDA IgG is 1:320.1 However, the more invasive, lumbar puncture can yield more sensitive and specific results.3 Analysis of diseased patient’s cerebrospinal fluid (CSF) has shown 80% will display mild-to-moderate lymphocytic pleocytosis and 50–60% of patients will be positive for oligoclonal bands.2 There is conflicting evidence behind the presence of serum IgG antibodies against the GluN1 subunit of NMDAR; however, they are almost always present in diseased patient’s CSF.3 Finally, the absence of antibodies LGI1 and Caspr2 in CSF have been linked with the disease.1

Imaging modalities have proven extremely useful in diagnosis. Electroencephalogram (EEG) will almost always be abnormal, and some diseased patients may display an “extreme delta brush” pattern.3 Magnetic resonance imaging (MRI) may display hyperintense signal in T2/FLAIR sequences in mesiotemporal focus or multifocal lesions in gray and white matter.1

In conclusion, if the previously proposed diagnostic criteria for anti-NMDA receptor encephalitis are met (see Table 21), neuroimmunology and oncology should be consulted. Patients should undergo work up to rule out underlying malignancy as various tumors (teratomas most commonly) have been associated with the disease. 3 If possible, tumors should be excised prior to treatment with intravenous immunoglobulin and/or corticosteroids. It is our hope that with this guide, more cases of anti-NMDA receptor encephalitis presenting with psychotic symptoms will be identified in psychiatry, and patients will receive life changing treatment.


Presenting symptoms
·      Age- <18 (37%)          

·      Psychosis (60%)

·      Autonomic abnormalities  

·      Impaired consciousness

·      Hypo/hyperactive catatonia

·      Stereotyped movements

·      Female:Male- 4:1

·      Headache/fever (70%)

·      Seizures (children>adults)

·      Memory deficits

·      Focal neurologic deficits

·      Hyponatremia

Serum ·    IgG anti-NMDA receptor antibody titer 1>320
CSF ·   Mild-moderate pleocytosis <100 WBC/mL (80%)

·   Mild-moderate increased protein concentration (30%)

·   Oligoclonal bands (50-60%)

·   Absence of autoantibodies against LGI1 and     Caspr2

MRI ·   Normal in 50-66% of cases

·   Hyperintense signal in T2/FLAIR sequences in mesiotemporal focus

·   Multifocal lesions in gray and white matter

EEG ·   Epileptic or slow wave abnormality

·   Extreme delta brush pattern

Table 1. Clinical, laboratory and image findings seen in anti-NMDA receptor encephalitis1, 3



Diagnostic Criteria1

Rapid progression (< 3 months) of working memory deficits, altered mental status or psychiatric symptoms  


One of the following:


New focal CSF findings


Seizures not explained by a previously known seizure disorder


CSF pleocytosis (white blood cell count >5 Zellen/mL)


MRI findings suggestive of encephalitis*


Alternative causes being excluded


Malignancy not required for diagnosis

*Hyperintense signal on T2 weighted FLAIR with sequences restricted to one or both medial temporal lobes or in multifocal involving, either/both grey and white matter

Table 2. Proposed diagnostic criteria for anti-NMDA receptor encephalitis1


  1. Steiner, J., Prüss, H., Köhler, S., Frodl, T., Hasan, A., & Falkai, P. (2020). Autoimmune encephalitis with psychosis: Warning signs, step-by-step diagnostics and treatment. The world journal of biological psychiatry: the official journal of the World Federation of Societies of Biological Psychiatry, 21(4), 241–254. https://doi.org/10.1080/15622975.2018.1555376


  1. Kayser, M. S., & Dalmau, J. (2016). Anti-NMDA receptor encephalitis, autoimmunity, and psychosis. Schizophrenia research, 176(1), 36–40. https://doi.org/10.1016/j.schres.2014.10.007


  1. Leypoldt, F., Armangue, T., & Dalmau, J. (2015). Autoimmune encephalopathies. Annals of the New York Academy of Sciences, 1338(1), 94–114. https://doi.org/10.1111/nyas.12553









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