Neuro-Ophthalmology & Neuro-Otology
May. 31, 2023
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Anti-NMDA receptor encephalitis is a disease occurring when antibodies produced by the body’s own immune system attack NMDA receptors in the brain. NMDA receptors are proteins that control electrical impulses in the brain. Their functions are critical for judgement, perception of reality, human interaction, the formation and retrieval of memory, and the control of unconscious activities (such as breathing, swallowing, etc), also known as autonomic functions.
Antibodies are an important part of the body’s defense system. All healthy individuals produce antibodies against viruses, bacteria or tumors. Under normal circumstances, the body prevents production of antibodies against its own (‘host’) tissues. In some individuals, however, antibodies that target the host may be produced. When this occurs the patient is said to have an “auto immune” (i.e., originating from one’s self) disease.
In anti-NMDA receptor encephalitis antibodies are generated against NMDA receptors and go on to attack these receptors where they are found in their highest concentration: within the brain. The reasons why anti-NMDA receptor antibodies are formed is not yet fully understood.
Anti-NMDA receptor encephalitis may be associated with a tumor, and may therefore be referred to as a “para (ie, associated with) neo (ie, new) plastic (ie, growth”) disease. If a tumor is found, it is most often a benign (i.e., not cancerous) tumor of the ovary. The most common tumor type is a teratoma. However, unlike other tumors, it may contain many different types of body tissues (including brain tissue!) A tumor is more likely to be found in young women who become sick during their childbearing years, and is less likely in very young (age 0 to 10) and older (more than 50 years) individuals. Anti-NMDA receptor encephalitis affects more women (80%) than men (20%). Tumors may be found in men. When these occur they are usually found in the testes. Other types of tumors that have been associated with anti-NMDA receptor encephalitis include lung cancer, thyroid tumors, breast cancer, cancer of the colon, and neuroblastoma.
The role of the tumor in producing Anti-NMDA receptor encephalitis is not fully known and is the subject of ongoing research. What is known is that most tumors associated with anti-NMDA receptor encephalitis contain neural tissue (tissue containing cells identical to that found in the brain), and NMDA receptors. It is presumed that antibodies are initially formed against NMDA receptors found within tumors, and then attack similar-looking receptors in the brain producing the symptoms and signs associated with anti-NMDA receptor encephalitis.
Tumor removal is a very important part of treatment.. Patients who have a tumor that is removed, recover faster and are less likely to experience a recurrence (or relapse) of their disease than those in whom no tumor is found. All patients suspected of suffering from anti-NMDA receptor encephalitis should be screened for the presence of tumors. This is usually done with imaging (CT or MRI) of the chest, abdomen and pelvis. Women should also receive an ultrasound of the ovaries, and men should receive an ultrasound of the testes. Even after removal, tumors can regrow. Therefore, people with anti-NMDA receptor encephalitis should be checked periodically for the presence (or recurrence) of tumors.
In many people with anti-NMDA receptor encephalitis a tumor is never found. This may be because the tumor is too small to detect with imaging techniques, or because it has been destroyed by the immune system, or there is no tumor. In cases not associated with a tumor, it is not known what causes anti-NMDA receptor encephalitis.
The vast majority of patients experience a combination of symptoms and signs from the above list. Symptoms may come and go over the course of the illness. Rarely (<5% of cases), psychiatric symptoms (hallucinations, mood disturbances, delusions) may be the only symptom of anti-NMDA receptor encephalitis.
Many people complain of flu-like symptoms around the time that their disease begins. The possibility that an infection triggers or contributes to the development of anti-NMDA receptor encephalitis is being actively considered in research.
The majority of cases occur in young adults and children, although cases have been diagnosed in people in their 80’s! Females are approximately four times more likely to be affected than males.
A diagnosis of anti-NMDA receptor encephalitis requires antibodies to be detected in the body fluids of someone with symptoms consistent with anti-NMDA receptor encephalitis. Antibodies may be found in either blood or spinal fluid. Tests on the spinal fluid are more accurate than those on the blood. Therefore, if blood tests are negative, the spinal fluid should be tested before concluding that the patient does not have anti-NMDA receptor encephalitis.
Imaging is an important part of the evaluation of a patient with suspected anti-NMDA receptor encephalitis and should include studies looking at the brain (MRI) and studies looking at the body for an associated tumor.
Patients diagnosed with anti-NMDA receptor encephalitis need to be admitted to hospital where they can be monitored and attended to by a team of doctors, nurses, and other health professionals. Although every patient’s disease, symptoms, and experience is different, most are treated with medications that reduce the levels of antibodies in the blood and spinal fluid. These include corticosteroids (“steroids”), intravenous immunoglobulin (antibodies collected from healthy blood donors that bind host antibodies), and plasmapheresis (PLEX; that involves use of a machine to filter antibodies out of the host’s blood).
Occasionally, the use of more powerful drugs are required to eliminate antibodies. The drugs most commonly used to treat anti-NMDA Receptor Encephalitis are rituximab (Rituxin®) and cyclophosphamide 9 (Cytoxin®). Many other medications may also be required, including those used to control blood pressure, stop seizures, ease anxiety, improve sleep, and to treat hallucinations or abnormal behaviors.
Medications may need to be continued after the patient has begun to recover.
Although anti-NMDA receptor encephalitis is a serious life-threatening disease, the majority of patients who receive prompt diagnosis and treatment go on to make a good recovery.
Recovery is generally slow and may occur over months or even years. The recovery process is often complicated by many ups and downs, and by fears of relapse or re-emergence of symptoms. It is important during this period that the patient continues to be closely monitored by their physician. Even after recovery is well-established, routine medical assessments remain very important, including repeat imaging to ensure that no tumor is found. Unfortunately, not all people affected by anti-NMDA receptor encephalitis recover.
The disease can be fatal, with most patients dying due to cardiac arrest (stopping of the heart), or from complications associated with long stays in hospitals and the use of powerful immune-suppressing medications (which makes people more susceptible to serious infections). Some patients may not recover completely, and friends and family may notice changes in the patient’s personality or some other aspect that is different from before the onset of illness.
Relapses may occur in 14% to 25% of patients. Although no test is available to predict which patients will experience a relapse, research has shown that relapses are more likely to occur in patients in whom a tumor has not been identified, and in those whom were not treated with immune-suppressing medications during their first attack.
Immune suppressing medications may be taken for prolonged periods of time (even after recovery) to prevent a relapse.
When relapses occur, they usually involve the same symptoms experienced during the first attack–although the symptoms may be less severe, and may not all occur at the same time, or in the same order as before.
Currently, there is no evidence to suggest that anti-NMDA receptor encephalitis is hereditary. Autoimmune diseases may, however, be more likely in some families. Research is ongoing considering a possible genetic link in anti-NMDA receptor encephalitis.
This information was developed by the The Anti-NMDA Receptor Encephalitis Foundation. Accessed June 16, 2022.