An NMDA antibody is a type of autoantibody, an immune protein that incorrectly targets the body’s own tissues. These antibodies attack specific structures in the brain called N-methyl-D-aspartate (NMDA) receptors. This attack disrupts normal signaling between brain cells, leading to inflammation, a serious neurological condition, and a cascade of neurological and psychiatric symptoms.
The Function of NMDA Receptors
NMDA receptors are proteins found on the surface of neurons that are important to brain function. They act like gates that control the flow of electrical signals and ions between nerve cells, a process that is important for what is known as synaptic plasticity. Synaptic plasticity is the brain’s ability to strengthen or weaken connections between neurons, which is the cellular basis for learning and memory formation.
These receptors are densely located in brain regions responsible for higher cognitive abilities, such as the hippocampus and cerebral cortex. Their proper function supports processes like judgment, perception of reality, memory, and learning. When NMDA receptors are activated, they allow calcium ions to enter the neuron, triggering intracellular events that lead to long-lasting changes in synaptic strength. This mechanism allows the brain to adapt based on experience.
Causes of Anti-NMDA Receptor Encephalitis
The production of NMDA antibodies is often triggered by the immune system’s response to a tumor. In many cases, particularly in women, the condition is associated with an ovarian teratoma. This type of tumor can contain neural tissue with NMDA receptors. The immune system generates antibodies to attack the tumor, but these antibodies then cross-react with the NMDA receptors in the brain.
This paraneoplastic syndrome, where the cancer indirectly causes neurological symptoms, is a primary cause. However, in many individuals, including men and children, a specific trigger cannot be identified, and these cases are considered idiopathic. In some instances, viral infections, like the herpes simplex virus, are thought to precede the condition, suggesting an immune response to a virus may mistakenly create NMDA antibodies.
Symptoms and Progression
The illness caused by NMDA antibodies, known as anti-NMDA receptor encephalitis, progresses over days to weeks. It often begins with psychiatric symptoms that can be mistaken for a primary mental health disorder. Patients may experience hallucinations, seeing or hearing things that are not there, and can be admitted to psychiatric facilities before the true cause is known. Initial signs can include:
- Sudden and severe anxiety
- Paranoia
- Delusions
- Agitation
- Bizarre behaviors
Following this initial phase, the illness escalates to include severe neurological symptoms. Seizures are common and can be difficult to control with standard medications. Patients frequently develop movement disorders, known as dyskinesias, which involve involuntary writhing or twitching of the face, limbs, and torso. Speech can become disordered or lost, and cognitive function and memory deteriorate.
As the condition advances, it can impact autonomic functions, which are the body’s automatic processes. This may lead to dangerous fluctuations in heart rate, blood pressure, and body temperature, as well as breathing difficulties that may necessitate mechanical ventilation. Many patients enter a state of unresponsiveness or catatonia, requiring intensive care. The progression to a life-threatening state can be swift.
Diagnosis and Treatment
A definitive diagnosis of anti-NMDA receptor encephalitis is made by testing for the specific antibodies in a patient’s cerebrospinal fluid (CSF), which is collected through a lumbar puncture, also known as a spinal tap. While blood tests can also be used, antibody testing in the CSF is more sensitive and specific. To support the diagnosis and rule out other conditions, physicians use brain imaging like magnetic resonance imaging (MRI) and electroencephalography (EEG). An EEG may show a specific pattern called “extreme delta brush.”
Treatment is a two-pronged approach that focuses on removing the antibodies and suppressing the immune system’s attack. First-line therapies include high-dose corticosteroids, intravenous immunoglobulin (IVIG), and plasmapheresis, which filters antibodies out of the blood. If an ovarian teratoma or another tumor is found, its surgical removal is a standard part of treatment and can lead to significant improvement.
If a patient does not respond adequately to these initial treatments, second-line therapies are administered. These include medications like rituximab or cyclophosphamide. Early initiation of these treatments is associated with better outcomes, so therapy often begins as soon as a probable diagnosis is made, even before antibody test results are confirmed.
Recovery and Long-Term Outlook
Recovery from anti-NMDA receptor encephalitis is often a slow process, taking months or even years. Patients typically regain functions in the reverse order that they were lost; for example, autonomic stability and motor control may return before cognitive and psychiatric functions fully recover. The most significant improvements are often seen early after the acute phase, though progress can continue for several years.
Intensive rehabilitation is a large component of recovery. This involves a multidisciplinary team providing physical, occupational, and speech therapy to help patients regain lost skills. Cognitive rehabilitation is also necessary to address persistent deficits in memory and executive function. Despite the severity of the illness, a substantial number of patients, especially those who receive prompt diagnosis and treatment, can make a significant or even full recovery.
Relapses can occur, sometimes years after the initial episode, and require re-evaluation and further treatment. Many survivors face ongoing challenges, including cognitive difficulties, anxiety, and depression. However, with comprehensive care and long-term support, many are able to return to school or work and resume their lives.