The anti-NMDAr antibody (ab), was first identified in 2007 by Dr. Josep Dalmau. It is now believed to be the most common type of autoimmune encephalitis. Some patients experience a prodromal phase when the disease is developing with symptoms of viral-like or flu-like illness that usually presents 1-2 weeks before the development of psychiatric symptoms. It is not known whether the symptoms are due to NMDAR dysfunction, the systemic immune response to autoimmune disease or secondary responses to a viral infection which later precipitate autoimmune disease as seen in herpes simplex virus (HSV).

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NMDA receptors are proteins that control electrical impulses in the brain. Their functions are critical for judgement, perception of reality, human interaction, the NMDA receptor is essential for the development of new memory and retrieval of memory so patients later have no memory of certain times in their life while the disease was occurring.  Speech production is affected; it is described like aphasia but it does not fit with any type of aphasia.  Children may become almost mute. The control of unconscious activities such as breathing and swallowing, also known as autonomic functions, is impaired.

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The presentation of NMDAR encephalitis in children with behavioral abnormalities may initially suggest autistic regression, early onset schizophrenia, or childhood disintegrative disorder.  Presentations with adults may initially suggest undiagnosed Bipolar disorder, or recreational drug or alcohol abuse. Compared with adults, children more often present initially with abnormal movements or seizures, and then in the ensuing days or weeks progress to develop a syndrome similar to that of the adults.  In patients older than 45 years, the clinical picture is similar to that of younger patients, but the outcome is less favorable. In this age group, 23% of patients had an underlying tumor (carcinomas instead of teratomas), and delays in diagnosis and treatment were more frequent than in younger patients. 50% of young women of childbearing years had a teratoma.  

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Most patients with autoimmune encephalitis respond within weeks to first-line treatments, but anti-NMDAR encephalitis patients are the slowest among autoimmune encephalitis to respond.  For the 47% of patients who do not respond to first-line treatments, a second-line immunotherapy is started with rituximab or cyclophosphamide or both. The outcome of the second-line immunotherapy in patients is improved in 65% of cases.  Generally, the frequency of improvement is better for patients with tumor (80%) when compared to patients without tumor (48%). Patients without tumors consequently require more often a second-line immunotherapy.  Despite this second-line treatment, relapse can occur in 20%–25% of the case. To prevent relapses, immunosuppressive treatment can be continued with mycophenolate mofetil or azathioprine during 1 year.

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There is an association of higher CSF titers for teratoma and higher CSF tiiters and worse outcomes.  High CSF titers can also be associaated with relapses. Usually when the patients start to recover from the autonomic dysfunction, they start getting better.  Recovery is slow, greater than two years, and occurs in inverse order of symptom development.  Patients are then left with several executive dysfunctions that can last for a long time; some of which they may not recover.