Must-read: Anti-NMDA Receptor Encephalitis

August 28, 2013, 1:35 pm


Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis: an etiology worth considering in the differential of delirium. Punja M et al. Clin Toxicol 2013 Aug 20 [Epub ahead of print]


This important paper is a must-read, especially for toxicologists who have not heard of this under-appreciated neurological disorder. (I was not aware of it until several days ago, when I found out that a friend of a relative had received the diagnosis.) Anti-NMDAR encephalitis was first described in 2005. Cases often present with altered mental status, autonomic instability, increased muscle tone, and movement disorders. Since initial behavioral and cognitive changes are easily mistaken for a new psychiatric diagnosis and treated with neuroleptics, toxicologists are frequently called on to evaluate these patients for neuroleptic malignant syndrome (NMS). This paper describes two such patients.

Anti-NMDAR encephalitis typically affects younger patients. In one series of 100 cases, the median age was 23 years (range, 5-76 years); over 90% were female. In that series, patients presented with psychiatric symptoms or memory disorders (100%), decreased levels of consciousness (88%), dyskinesias (86%), and seizures (76%), All had antibodies in the cerebrospinal fluid against subunits of the NMDA receptor. Since these receptors are prevalent in the limbic system and the hippocampus, patients develop signs and symptoms of limbic encephalitis: memory loss, hallucinations, irritability, agitation, sleep disturbance and seizures.

Anti-NMDAR encephalitis is frequently — but not always —a paraneoplastic syndrome, often associated with ovarian teratoma. (Hence the over-representation of women among reported patients.) Some patients have a nonspecific prodrome with headache or symptoms suggesting a respiratory infection:

Initial symptoms of NMDAR encephatlitis are most commonly speech disorders, memory deficits, and behavioral changes. As seen in both of our patients, these symptoms may be initially attributed to psychiatric disease or drug abuse, leading to a delay in diagnosis. While there is a range of severity of symptoms, there is often a striking progression of new and increasingly severe symptoms typically occurring over a 5-15 day period.

Diagnosis is often suspected when patients presumed to have NMS, intoxication, or withdrawal don’t respond to appropriate treatment, and is confirmed by demonstrating anti-NMDAR subunit antibodies in the CSF. Initial therapy includes high-dose steroids, IV immunoglobulin, and plasma exchange, as well as removal of any causative neoplasm if present. In approximately 75% of patients manifestations resolve with treatment. The reported mortality rate is up to 6%.

The authors conclude:

Medical toxicologists should consider anti-NMDAR encephalitis in the differential diagnosis of patients with new-onset signs and symptoms of encephalopathy. As some patients may initially be diagnosed with a primary psychiatric disease and treated with neuroleptics, concern for NMS may prompt the initial toxicological consultation, as was the case with our two patients.

Chris Nickson has posted an excellent synopsis of anti-NMDAR encephalitis at Life in the Fast Lane. That post is also a must-read and can be accessed by clicking here.