Anti-NMDA (N-methyl-D-aspartate) receptor encephalitis is autoimmune disorder, in which antibodies are directed against the NMDA receptor in the brain, resulting in neurologic and psychiatric symptoms.
NMDA receptors play a critical role in normal brain function. NMDA receptors are present throughout the brain and are a key receptor in signaling from neuron to neuron. Therefore, when they are prevented from working normally by an antibody, multiple areas of the brain are affected. This is why you can have very different symptoms affecting different parts of the brain (seizures, movement disorder, psychosis, memory loss).
The identification of anti-NMDA receptor (anti-NMDAR) encephalitis in 2007 by Dr. Dalmau made it possible to recognize that some patients with a rapid onset (weeks to months) of psychiatric symptoms, cognitive impairment, seizures, abnormal movements, or coma of unknown cause, had this autoimmune disease.
Anti-NMDAR encephalitis is the most common form of antibody-associated autoimmune encephalitis. It can affect people of all ages, though the highest rates are in children and young adults, with 37% of patients less than 18 years of age. It affects women more frequently than men (with a female to male ratio of around 8:2).
The disease may start with flu-like symptoms, followed by fairly rapid (over days to weeks) development of other symptoms such as psychiatric symptoms (often hallucinations, delusions, paranoia, etc), memory problems, movement disorders, seizures, and even changes in heart rate, blood pressure, or even coma. If psychiatric symptoms are a major symptom, some patients are first admitted to psychiatric hospitals before they are diagnosed with encephalitis. While some patients may be diagnosed and treated as outpatients, most require hospitalization and even intensive care unit admissions.
To make a diagnosis many tests need to be done to look for signs of brain inflammation and dysfunction. MRI scans should be done, though in 50% of the patients it will be normal. Electroencephalograms (EEG) are abnormal in most patients, usually showing non-specific, slow, and disorganized activity and/or electrographic seizures. The cerebrospinal fluid (CSF) will often show increased white blood cells or other markers of inflammation, with the majority of patients showing one or more markers of autoimmunity/inflammation.
Antibodies can be detected in spinal fluid and blood, but in patients with NMDAR encephalitis, they should be present in the CSF. When NMDAR antibodies are present only in the blood, they may be a false positive. In about 15% of patients the antibodies are only found in the CSF. Therefore, if a patient is suspected of having anti-NMDAR encephalitis and only blood was tested and was negative for antibodies, the CSF should be examined. Brain biopsy is not required to make a diagnosis of anti-NMDAR encephalitis. Once it is determined that a patient does not have anti-NMDAR encephalitis, brain biopsy may be done to diagnose other conditions.
Teratomas (usually a benign tumor) is seen in some people, especially ovarian teratomas in younger women, (more frequent in women older than 18 years), and less commonly testicular teratoma’s in men.
Treatment is classically described as first line immunotherapy (corticosteroids, intravenous immunoglobulin, or plasma exchange) and second-line immunotherapy (cyclophosphamide or rituximab, or both). Not all patients need second line therapy, as some improve with first line treatments alone.
Patients with teratomas who are treated with removal of the tumor and immunotherapy respond faster to treatment and less frequently need second line therapy compared to patients without a tumor or whose tumors were not removed who receive similar initial immunotherapy.
Treatment with psychiatric medications and epilepsy drugs are often needed. It may take a long time to recover from the disease. The symptoms often resolve in the opposite order of the way they started, and in some patients, you can see a worsening of behaviors or movements as the patient progresses through the recovery phase.
About 80% of patients improve with immunotherapy and, if needed, tumor removal, but the recovery can be slow. There is a risk that the disease may flare up again in approximately 15% of patients. In these cases, the patients often respond again to treatment.
Myrna Rosenfeld, MD, Institute for Biomedical Research (IDIBAPS) of the University of Barcelona, Spain, Adjunct Professor of Neurology at the University of Pennsylvania.
A Conversation with Susannah Cahalan and Dr. Souhel Najjar
AutoImmune Encephalitis: Patient Perspective, Susannah Cahalan
Dr. Dalmau discusses anti-NMDAR encephalitis.
Dr. Maarten Titulaer discusses Anti-NMDAR Encephalitis
It was almost exactly ten years ago that I rushed home from a coffee shop, paranoid and terrified, and my journey with autoimmune encephalitis began. A college sophomore, I ended up in the ER and then a psychiatric ward, eventually “diagnosed” with Psychosis: Unknown.