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Brain Pain: Unlocking the Mysteries of Autoimmune Encephalitis

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Dr. Anjan Nibber sheds some light on a rare disease, garnering some publicity, and offers a lesson about brain health in this week’s blog

In 201healthy-brain-680x5501 the world mourned the death of Knut the polar bear, who had stolen the hearts of everyone who had visited the Berlin Zoo or who had followed his high profile career of modeling alongside celebrities like Leonardo DiCaprio.  In 2012, Sussanah Calahan released her memoir Brain on Fire: My Month of Madness, which chronicled her struggle with NMDA receptor mediated-encephalitis.  It was soon discovered that the same disease that Sussanah Calahan wrote about was the very disease that resulted in the death of Knut the bear.  In this blog we will discuss what encephalitis is, and more specifically what NMDA receptor mediated encephalitis is.

What is encephalitis?

Very simply put, encephalitis is a sudden onset inflammation of the brain or regions of the brain.  While relatively rare, the incidence of the disease varies throughout the world, with approximately 7.4 new cases of acute encephalitis per 100,000 per year in the Western countries.

Patients with encephalitis can present with a variety of symptoms, depending on which are of the brain is affected.  Patients with limbic encephalitis for instance suffer from memory impairments as the limbic regions of the brain (amygdala, hippocampus) are affected.  Other common symptoms of encephalitis include headache, drowsiness, fever and fatigue.  Patients are often diagnoses via brain scans, EEG (a method to monitor brain activity), or laboratory tests using cerebral-spinal fluid (CSF), blood or urine analysis.  

There are a variety of causes of encephalitis, such as viral infections (rabies virus, herpes-simplex virus, poliovirus, measles virus, etc.), bacterial infections (bacterial meningitis, syphilis, etc.), parasitic/protozoal infestations or autoantibodies.  Depending on the cause, patients will be treated with antiviral therapies, antibodies and/or steroids to help reduce brain inflammation.

Autoimmune Encephalitis

Autoimmune encephalitis comprise a rapidly-expanding group of central nervous system diseases. In the last 15 years, antibodies that target ion channels, ion channel-associated proteins, and receptors expressed in the brain have been discovered.  One of the most famous of these diseases is NMDA receptor encephalitis.

NMDA receptor mediated encephalitis is caused by an autoimmune reaction to the NMDA receptor in the brain, important for controlling synaptic plasticity and normal memory function.  The disease was first characterised in a group of young women that had ovarian teratomas (tumours) and suffered from psychiatric problems.  Since then, NMDA encephalitis has been observed in a variety of age ranges, in both men and women, and in other species!

Patients can experience prodromal symptoms such a fever and headaches prior to onset of the disease.  During the initial stage, the symptoms often worsen and patients may experience behavioural abnormalities.  Agitation, paranoia and psychosis are all commonly experienced, these were some of the initial symptoms that Susannah Calahan recalls suffering from in her memoir.  Seizures, memory and speech problems, and ataxia, loss of consciousness may all follow at later stages.  As a relatively newly understood disease patients often remain undiagnosed for a long period of time.  In fact, Knut was only diagnosed following an autopsy.  A closer look at his video footage showed that the poor bear had suffered from a seizure, causing him to fall into a pool and eventually drown. This was the first case of the disease discovered in a non-human animal!

Patients can often be diagnosed by carrying out cell-based lab tests, which detect the presence of antibodies to the NMDA receptor from blood and CSF samples.  While optimal treatment strategies still need to be explored, clinical studies have shown that many patients treated with immunomodulatory regimens (steroids, plasma exchange) show neurological improvement.  Natural anti-inflammatories such as curcumin and boswellia are being considered as well.   

What causes this disease is of great interest.  Some patients have underlying tumors (usually ovarian teratomas), and these tumor cells often express the NMDA receptor found in the CNS.  As such, the body generates antibodies to the NMDA receptor to help fight off these cancerous cells. However, there are some patients with NMDA encephalitis that do not have a tumor, and the cause in these patients remains unclear.  In addition, how these antibodies gain access to the brain is also a hot topic of debate.  As mentioned above, some patients suffer from prodromal symptoms, which may be caused by infection.  Infections may in turn compromise the integrity of the blood-brain barriers, allowing antibodies to gain access to the brain. Prevention of these infections with natural immune support, may therefore mitigate the progression of the disease.

The complexity of this disease illustrates how important understanding a disease process is in developing treatments. Further, natural treatments may still be applicable in treating even highly complex diseases, an area in which alternative care is often disregarded. Through supporting the immune system, reducing inflammation, accessing the blood brain barrier, scientists are venturing into new territory for treatments.

About the Author:

Dr. Anjan Nibber is a Scientific and Research Consultant for AOR.  Dr. Nibber holds a BSc (Hons) in Biological Sciences from the University of Calgary and a DPhil in Clinical Neurology from the University of Oxford.  Anjan has extensive research, business, and communications experience. Anjan has worked as a medical researcher in respiratory medicine and is a Co-founder and Editor-in-Chief of Career Insight, a magazine publication supported by Oxford Careers Service.

1 Comment

  1. Dr. Andrew Caine Reply

    A very insightful article! This is reminiscent of work I did in my clinical trials at Tulane.

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