Anti-NMDA receptor encephalitis

Anti-NMDA receptor encephalitis is a type of brain inflammation due to antibodies. Early symptoms may include fever, headache, and feeling tired. This is then typically followed by psychosis which presents with false beliefs (delusions) and seeing or hearing things that others do not see or hear (hallucinations). People are also often agitated or confused. Over time seizures, decreased breathing, and blood pressure and heart rate variability typically occur. Anti-NMDA receptor encephalitis is a type of brain inflammation due to antibodies. Early symptoms may include fever, headache, and feeling tired. This is then typically followed by psychosis which presents with false beliefs (delusions) and seeing or hearing things that others do not see or hear (hallucinations). People are also often agitated or confused. Over time seizures, decreased breathing, and blood pressure and heart rate variability typically occur. About half of cases are associated with tumors, most commonly teratomas of the ovaries, while the cause in others cases is unclear. The underlying mechanism is autoimmune with the primary target the GluN1 subunit of the N-methyl D-aspartate receptors (NMDAR) in the brain. Diagnosis is typically based on finding specific antibodies in the cerebral spinal fluid. MRI of the brain is often normal. Misdiagnosis is common. Treatment is typically with immunosuppresive medication and, if a tumor is present, surgery to remove it. With treatment about 80% of people have a good outcome. Outcomes are better if treatment is begun earlier. Long term mental or behavioral problems may remain. About 4% of those affected die from the condition. Reoccurrence occurs in about 10% of people. The condition is relatively common. About 80% of those affected are female. It typically occurs in adults less than 45 years old but can occur at any age. The disease was first described by Josep Dalmau in 2007. Prior to the development of a symptom complex that is specific to anti-NMDA receptor encephalitis, people may experience prodromal symptoms, including headaches, flu-like illness, or symptoms similar to an upper respiratory infection. These symptoms may be present for weeks or months prior to disease onset. Beyond the prodromal symptoms, the disease progresses at varying rates, and patients may present with a variety of neurologic symptoms. During the initial stage of the disease, symptoms vary slightly between children and adults. However, behavior changes are a common first symptom within both groups. These changes often include agitation, paranoia, psychosis, and violent behaviors. Other common first manifestations include seizures and bizarre movements, mostly of the lips and mouth, but also including pedaling motions with the legs or hand movements resembling playing a piano. Some other symptoms typical during the disease onset include impaired cognition, memory deficits, and speech problems (including aphasia, perseveration or mutism). The symptoms usually appear psychiatric in nature, which may confound the differential diagnosis. In many cases, this leads to the illness going undiagnosed. As the disease progresses, the symptoms become medically urgent and often include autonomic dysfunction, hypoventilation, cerebellar ataxia, loss of feeling on one side of the body, loss of consciousness, or catatonia. During this acute phase, most patients require treatment in an intensive care unit to stabilize breathing, heart rate, and blood pressure. One distinguishing characteristic of anti-NMDA receptor encephalitis is the concurrent presence of many of the above listed symptoms. The majority of patients experience at least four symptoms, with many experiencing six or seven over the course of the disease. The condition is mediated by autoantibodies that target NMDA receptors in the brain. These can be produced by cross reactivity with NMDA receptors in teratomas, which contain many cell types, including brain cells, and thus present a window in which a breakdown in immunological tolerance can occur. Other autoimmune mechanisms are suspected for patients who do not have tumors. Whilst the exact pathophysiology of the disease is still debated, empirical evaluation of the origin of anti-NMDA receptor antibodies in serum and cerebrospinal fluid leads to the consideration of two possible mechanisms. These mechanisms may be informed by some simple observations. Serum NMDA receptor antibodies are consistently found at higher concentrations than cerebrospinal fluid antibodies, on average ten times higher. This strongly suggests the antibody production is systemic rather than in the brain or cerebrospinal fluid. When concentrations are normalized for total IgG, intrathecal synthesis is detected. This implies that there are more NMDA receptor antibodies in the cerebrospinal fluid than would be predicted given the expected quantities of total IgG.