What is Anti-NMDA Receptor Encephalitis?
Encephalitis, in general, is an inflammation of the brain tissue.
An inflammation is a sign that the body is fighting an infection. The immune system kicks into action and white blood cells rush to the specific region where infection is taking place. This rush of blood results in a red, swollen, warm and painful region that are the 4 tell-tale signs of an inflammation:
An inflammation is red because of the drastically increased blood flow to the area.
It is swollen because of said fluid increase.
It’s warm for this same reason.
Lastly, an inflammation is painful because the swelling puts pressure on the nerves in the area.
It may be highly uncomfortable, and it might even restrict your movement, but an inflammation actually means that your immune system is working for you—protecting your body from diseases and infections.
Encephalitis, the inflammation of the brain tissue, means that some virus is attacking that specific part of the body. A virus directly attacking the brain or the spinal cord is called Primary Encephalitis. If the infection starts somewhere else and then travels to the brain, it is called Secondary Encephalitis.
Different types of viruses are said to cause encephalitis. Common viral diseases like mumps, measles, rubella and chickenpox can be culprits. (That’s why early age vaccination is very important.) Also, viruses transmitted by insects, such as the West Nile Virus, have been known to cause brain inflammation.
However, Anti-NMDA Receptor Encephalitis is a different thing. It is an autoimmune condition.
An autoimmune disease is when the body produces antibodies that, instead of attacking viruses and bacteria, attacks healthy cells and tissues. This type of encephalitis is not caused by any foreign virus, but a case of the body mistakenly attacking itself.
Anti-NMDA Receptor Encephalitis was first identified in 2007 by Dr. Josep Dalmau and colleagues from the University of Pennsylvania. They found antibodies that specifically attack the NMDA receptors in the brain. How and why this happens is not yet fully understood and are subjects of ongoing medical research.
NMDA receptors (N-Methyl-D-Aspartate receptor or NMDAR) are very important because they facilitate the interactions or “conversations” between different cells in the brain. These receptors are therefore vital for cognitive functions like learning, memory, perception, and autonomic processes like breathing and swallowing.
Secondary Anti-NMDA Receptor Encephalitis is often associated with a tumor, usually ovarian teratoma. It is believed that in these cases, antibodies are first produced to attack NMDA receptors found in the tumor. These antibodies then travel to the brain where there is the highest concentration of NMDA receptors.
Signs and Symptoms
Persons suffering from Anti-NMDA Receptor Encephalitis may present a combination of these symptoms:
Very early signs include the patient experiencing fever, headache and fatigue. These are called “prodromal symptoms.” They are early indicators that come before the full development or onset of the condition. Anti-NMDA Receptor Encephalitis progresses at varying rates, and such flu-like symptoms may appear weeks or even months before more severe symptoms emerge.
It’s difficult to suspect the condition early on because the symptoms can be written off as the patient having the common flu.
The diagnostically significant symptoms come in the wake of the flu-like illness.
Because the condition affects the normal functioning of the brain, things like short-term memory will be affected. Patients will soon suffer from hallucinations and delusions—describing events that never happened, seeing and reacting to things that are not actually there, and hearing sounds and voices that are non-existent.
The patient appears confused and agitated. There will be bouts of paranoia, with the patient reporting that somebody is out to get him/her. There is generally a breakdown in normal, logical and clear thinking, where the patient experiences extreme difficulty determining what is real and what is not.
That being said, the people around will consider the patient as “going crazy” or “being possessed by the devil.”
In addition to these abnormalities, speech will also be so affected, that the person experiences difficulty expressing coherent thoughts or statements. Worse, he or she might not be able to communicate at all.
Seizures and movement disorders
Patients often lose purposeful control of their bodies. Patients lose control of their arms, legs, tongue and mouth. The face will be twitching erratically. They will be writhing about, with arms and legs flailing in uncontrollable ways. Full body spasms are very common. These can be so severe that patients often need to be restrained and sedated to prevent them from harming themselves and the people around.
On the other side of the spectrum is catatonia. This is the prolonged cessation of movement that can last from several hours to days. The patient will be still and unresponsive, looking like a lifeless statue holding the same position for long periods of time.
Autonomic functions are those body processes that do not require conscious control. They include breathing, beating of the heart and digestion. With Anti-NMDA Receptor Encephalitis, the autonomic processes that help maintain health become erratic and may even completely stop. In extreme cases, the patient could stop breathing and require a ventilator for survival.
Control of the bladder and bowel movements are also lost.
According to The Encephalitis Society, 20%-30% of women with the disorder have an underlying tumor. Ovarian teratoma is the most common tumor found in affected women. Although it is often non-cancerous, the tumor is believed to stimulate the production of NMDA Receptor antibodies.
Tumors don’t automatically mean autoimmune encephalitis. While tumors found in other parts of the body like the breast, lung, thyroid, testes and colon have been implicated, by far, the most common tumor related to the condition is the ovarian teratoma found in women.
Diagnosis and Tests
Anti-NMDA Receptor Encephalitis is the subject of the book “Brain on Fire”—a 2012 New York Times best-selling autobiography by Susannah Cahalan, a writer for the New York Post. The book, which chronicles the author’s struggles with the autoimmune condition, was made into a film in 2016.
She was 24 at that time.
Anti-NMDA Receptor Encephalitis often affects young women.
According to the Anti-NMDA Foundation, 80% of those affected are women. Although the disorder can appear at any age, the median diagnostic age, according to one study, is 21. There are no exact figures as to its prevalence in the Philippines, but we do have documented cases which has raised awareness of this rare condition.
So, how does one diagnose Anti-NMDA Receptor Encephalitis?
A serologic blood test needs to be conducted. A serologic test will look for antibodies in the blood. A trained professional will draw a blood sample, and by performing various laboratory techniques, the different antibodies present in the blood can be identified.
In this case, your immunologists will be looking for the NMDA Receptor Antibody.
The test is highly reliable and accurate. However, if a test yields negative but there remains a strong reason to suspect Anti-NMDA Receptor Encephalitis, like when the symptoms mentioned above are present, a more invasive test could be recommended: Cerebro-Spinal Fluid Analysis.
Cerebro-Spinal Fluid Analysis
A CSF Analysis can look into the conditions of the brain and the spinal cord. The method of getting the fluid sample is called a “spinal tap” or a lumbar puncture.
It is a highly invasive procedure where a thin spinal needle is carefully inserted between the vertebrae. Fluid is then collected from the spinal column. The sample would go through a series of procedures to determine whether the specific NMDA Receptor Antibody is present.
A positive or a negative result would be deemed conclusive.
For patients diagnosed with secondary encephalitis, efforts should be made to surgically remove the tumor as soon as possible. This will eliminate the source of the antibodies and drastically lower its levels in the body. Prompt removal of the tumor results to a more positive long-term prognosis and a decreased chance of relapse.
Patients should also undergo primary treatment composed of:
These are a class of drugs that reduces the strength and effectivity of the patient’s immune system. If the immune system is mistakenly attacking the body, then immunosuppressants put that process in check. They, however, have a side effect. Because they generally lower the efficacy of the immune system, they also increase the chances of an infection. That said, the benefits outweigh the possible side-effects.
Corticosteroids are also given to help ease the inflammation.
They are a specific concoction of antibodies that is administered intravenously. Immunoglobulins help patients fight infection and are often used to treat autoimmune diseases.
This is also known as “plasma exchange” and works very much like the dialysis done for kidney patients. While dialysis cleans out the solutes and toxins from the blood, plasmapheresis takes out the harmful antibodies.
Blood is extracted through a needle connected to a tube which is then passed through a machine. The machine separates the plasma (which contain the antibodies) from the blood. Fresh and healthy plasma is mixed into the blood and pumped back to the body. Thus, the term “plasma exchange.”
Recovery takes around two years, with the most extreme of symptoms disappearing first. Psychosis might return every once in a while, leading family members to suspect that the treatment is not working. But overtime, a significant decrease of severity and frequency of attacks will be noticed.
Generally, prognosis is positive for patients diagnosed early and those who underwent aggressive therapies. In addition to first-line or primary treatments mentioned above, second-line drugs like rituximab and cyclophosphamide have been used where other therapies have failed.
In addition to conducting routine blood tests, BloodWorks Lab specializes in repro-immunological screening.
We are proud to be the first laboratory in the Philippines to also offer neurological tests like the Anti-NMDA Receptor Antibody Test and the Anti Acetylcholine Receptor (lgG) Antibody Test.