A diagnosis you can’t afford to miss

March 2, 2018, 1:14 pm


Antibody-Mediated Encephalitis. Dalmau J, Graus F. N Engl J Med 2018 Mar 1;378:840-851.


TPR has posted before about anti-NMDA receptor encephalitis, a must-know, can’t-miss, humbling diagnosis that is distressingly easy to overlook. Although it is not a toxicologic condition, all toxicologists and emergency physicians should be thoroughly familiar with its presentation and clinical course. Let me explain why.

NMDAR encephalitis often begins with behavioral changes, mood swings, and memory deficits in relatively young patients. According to this somewhat technical but excellent review, the median age is 21 years, with a 4:1 ratio of females to males. Because of the initial symptoms, patients are often diagnosed as having new-onset psychiatric disease. It is not unusual for these patients to then be treated with antipsychotic medication in an attempt to control abnormal and agitated behavior.

This is where a toxicologist may be consulted. As the authors point out in this review, patients with NMDAR encephalitis seem to have increased susceptibility to developing neuroleptic malignant syndrome (NMS) after receiving antipsychotics. When these patients then develop movement disorders, autonomic instability, and altered mental status, the toxicology service is brought in to advise about the treatment of NMS.

If the diagnosis of NMDAR encephalitis is not considered, the outcome can be catastrophic. As the authors of this review note “spontaneous clinical improvement is infrequent.” Early treatment with immunotherapy can result in a good outcome. In the case of anti-NMDAR encephalitis, diagnosis is confirmed by finding specific antibodies cerebrospinal fluid. Lumbar puncture is essential, since testing serum for these enzymes yields a false negative in as many as 14% of cases. Optimal treatment has not yet been defined, but current regimens begin with glucocorticoids, IV immune globulin, and plasma exchange transfusion . In resistant cases, medications such as rituximab and cyclophosphamide can be used. It is also critically important to find and remove associated tumors — most commonly teratomas in young women.

This review article is well worth reading, but too detailed and technical to serve as a good introduction to this very important condition. It also covers many other forms of autoimmune encephalitis. Those looking for an introduction to anti-NMDAR encephalitis can consult the following:

One more essential read is Brain on Fire, an account of anti-NMDAR encephalitis from the patient’s point of view. Written by a journalist who was stricken with the condition before much was known about it, the book is so vivid and unforgettable that after reading it you’re unlikely ever to miss the diagnosis again.

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