Once again, I have been honored to receive a guest post from advocate, co-founder of The Anti-NMDA Receptor Encephalitis Foundation and friend, Nesrin Shaheen. Read on to learn about the evolution of anti-NMDA and the amazing breakthroughs that have been discovered since the disease was first identified in 2007.

Erica Snyder

The movie, Brain on Fire (2016), based on the memoir by Susannah Cahalan entitled Brain on Fire: My Month of Madness (2012) ended abruptly.  In the movie’s final scenes, Susannah, played by Chloe Moretz, recovers from her ordeal—her “month of madness”—and several months of rehabilitation, and returns to work.  Her boss, the editor of the New York Post, played by Tyler Perry, asks her to write an article about her experience (which would eventually become the inspiration for the book, and subsequent movie, about her ordeal). The movie ends there, and in all honesty, I felt as if I were left hanging; perhaps, because I knew that this is where the more amazing story began…

It was October 4, 2009 when the article “My Mysterious Lost Month of Madness” was published in The New York Post (http://nypost.com/2009/10/04/my-mysterious-lost-month-of-madness/).  At the time, my daughter was recovering from her second relapse with anti-NMDA receptor encephalitis (NMDARE) and was still hospitalized on the youth psychiatric ward, in an isolation room, with delusional and disinhibited behaviors. I had not been able to return to work and was spending a lot of time helping to launch a fledgling support group for patients and families battling NMDARE that had been created in January 2009 by Cami Tennant.  Her son had been diagnosed at 22 months of age—at the time, one of the youngest cases ever diagnosed—and apparently only the 101st known case of NMDARE. I was overjoyed that she had created this group and found myself spending more and more time there—so much so that Cami eventually asked me to become a deputy group administrator.  After some hesitation (I was already extremely tired and anxious about my daughter’s health), I accepted her offer and I haven’t looked back since.  I quickly recognized the value of such a group: as a repository of first-hand accounts from affected families, saving patient stories and articles to the files of the group, as well as starting what would eventually become the first crowd-sourced list of specialists with experience in the diagnosis and treatment of NMDARE and related forms of autoimmune encephalitis (AE).  We were only a handful of individuals in 2009. Now, nearly ten years later, we are almost 3,000 members strong.

In 2010, my daughter had her third relapse.  After five months in hospital, on the medical ward, having lost all physical and cognitive abilities, she was discharged home just prior to the Christmas holidays. Shortly afterward, I created a second Facebook support group for Canadians: The Anti-NMDA Receptor Encephalitis in Canada group.  I was still desperately trying to connect with other local people affected by this disease.  There seemed to be absolutely no one in Canada to speak with, let alone in my city of Ottawa.  I recall being at the hospital the day after Susannah’s article appeared (most likely someone on the group had found it and posted it), excitedly sharing a print-out with the doctors involved in my daughter’s care.  We were no longer just a small group of affected families discussing a rarity amongst ourselves. Thousands, if not millions, of people were reading that article around the world.  In Susannah we found a survivor who fought back a previously unknown illness, which in the past might have been attributed to demonic possession, hysteria or madness; we had a champion who would bring ANMDARE out of the shadows and to the forefront of modern medicine through her heartfelt and deeply personal writing. A floodgate had been opened and with the publication of the book three years later, came the deluge.

Understand, new diseases are not discovered every day! The microscopic antibody identified in 2007 by Dr. J. Dalmau within the blood and spinal fluid of 12 young women with psychoses and severe neurologic dysfunction, followed by the publication of his seminal paper in 2007, led to the unmasking of a disease that had been lurking about for millennia. For the first time, we had an explanation for the dramatic changes in personality, behavior and health that affected our loved ones: a rogue antibody made by the body, designed to seek and destroy NMDA receptors in the brain. And now, we had a name—a diagnosis—to rally around. We had hope!

We were the lucky ones who benefited from Dr. Dalmau’s findings.  At the time, his laboratory was the only one with the ability to test for NMDA receptor antibodies and it was for research purposes only.  This new disease, later described as a “swiftly moving dementia” (Day and Peery, 2013) with multiple and overlapping layers of neurologic and psychiatric symptoms would leave its victims in a deplorable state from which a return often seemed impossible. Once a diagnosis was made, quick and aggressive treatment was necessary, along with intensive and continuous management of the disease sequelae, including autonomic instability, involuntary movements, seizures and a plethora of psychiatric symptoms. The most severely affected fell into or were induced into a coma, usually to mitigate the effects of intractable seizures. Tragically, about 6% would die from secondary effects of the disease.

In the 11 years since Dr. Dalmau’s seminal paper, this amazing story has continued to unfold on a variety of different fronts. By January 2012, via the California Encephalitis Project, it was established retrospectively that NMDAR encephalitis had surpassed the known viral etiologies in young people enrolled in this project. These findings were recently re-confirmed via a study undertaken by the Mayo Clinic (2018).  In 2013, the first large observational cohort study of 577 patients was published by Dalmau and colleagues which studied treatment and prognostic factors for long-term outcomes in patients diagnosed with NMDARE. Also, in 2013, we learned that in addition to one of the established triggers of NMDARE, ovarian teratoma, the herpes simplex virus (the cause of herpes simplex encephalitis [HSE]) could also be another potential trigger. A significant number of patients who had been diagnosed with HSE and were recovering from this form of encephalitis were then relapsing into NMDAR encephalitis.

Because testing for antibodies can take up to three weeks depending on where one is (sometimes it may not be available at all), clinical guidelines were developed and published in 2016, in the prominent journal, The Lancet Neurology, entitled “A Clinical Approach to the Diagnosis of Autoimmune Encephalitis.” The purpose of this paper was to assist physicians in making a clinical diagnosis based on signs and symptoms and to initiate prompt treatment until test results arrive.

Further, it was recognized that NMDARE, with its very prominent psychiatric features, may be the key to solving the mystery of psychosis and how some psychiatric illnesses develop. According to preeminent specialists, Drs. Dalmau and Graus, “… knowing how antibodies cause symptoms, such as the psychosis caused by anti-NMDAR antibodies, may help to understand psychiatric diseases in which the same receptors may be altered by other mechanisms.” Although a cure has yet to be developed, we now know that awareness, leading to a quick diagnosis and initiation of treatment is believed to produce the best prognoses. What was once considered ultra-rare, has become not so rare after all.

As this amazing story continues to unfold, there are many still that are afflicted with AE in whom a specific antibody is never identified.  Dr. J. Masdeu, a professor of Neurology at Houston Methodist Hospital, is presently studying the role of auto-antibodies in psychotic illnesses. He believes that looking for the antibodies with a more sophisticated technique will determine the extent of misdiagnosis in this community. I hope that progress will be made in the coming years to identify more rogue antibodies, more triggers, and other mechanisms of disease, that will lead to more effective treatments for those afflicted.

Certainly, a lot has changed since I first became acquainted with NMDARE. As the mother of a survivor, administrator on two support groups and co-founder of The Anti-NMDA Receptor Encephalitis Foundation, Inc. (Canada) (http://www.antinmdafoundation.org/), I have seen the children of caregivers recover and join the support groups.  Many of these survivors, including my daughter, who battled the illness for five years, have returned to lead normal, successful lives; some even getting married and having children of their own. Others are contributing to the cause of raising awareness through their writings, artistic endeavors, and media appearances.  I have seen the caregivers of the affected recover as well—striking a victory over the anxiety and fear that comes with watching a loved-one battle through this catastrophic illness.  Some of the on- and off-line friendships that have sprung up, through shared hardship will, I suspect, become lifelong friendships and a triumph over anti-NMDA receptor encephalitis! Ultimately, the story of the evolution of this devastating, and morbidly fascinating, disease is far from over. New technologies, better treatment options, continued research and more awareness continue to push the disease to the forefront of the medical community and advances are being made in great strides. For those of us who have lived through it, the story continues until a cure is found.

References 

1. Day, Gregory S., Peery, Harry E., Autoimmune synaptic protein encephalopathy syndromes and the interplay between mental health, neurology and immunology. Health Science Inquiry. Volume 4/Issue 1/2013, 89-91.
2. Dalmau J, Tüzün E, Wu H, et al. Paraneoplastic anti-N-methyl-Daspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol 2007;61:25–36.
3. Gable, Mary S, et.al., The Frequency of Autoimmune N-Methyl-D-Aspartate Receptor Encephalitis Surpasses That of Individual Viral Etiologies in Young Individuals Enrolled in the California Encephalitis Project, Clinical Infectious Diseases, January 2012.
4. Dubey, D., et.al., Autoimmune Encephalitis Epidemiology and a comparison to Infectious Encephalitis. Annals of Neurology, January 2018.
5. Graus, Frances, et.al. A Clinical Approach to the Diagnosis of Autoimmune Encephalitis. The Lancet Neurology, Feb 19, 2016.
6. Dalmau, J and Graus, F, Antibody Mediated Encephalitis, New England Journal of Medicine, March 1, 2018, pg. 849.
7. Hixenbaugh, Mike. (2017, May 24). Do thousands with schizophrenia have a treatable immune disorder?. The Houston Chronicle. Retrieved from https://www.houstonchronicle.com/local/prognosis/article/Schizo-10941631.php,

8 Comments

  1. Anne

    Thank you! Just knowing we’re not alone make a difference. Keep up the good work, we need more awareness. My daughter was also in a pshych ward until we took her out without the doctors concent, was the best thing we did for her. She got diagnosed about a month after, after she was in ICU, they sent her to Toronto where she finally got her diagnosis’ and they treated her. I’m a big believer in following your gut feeling, trust yourself, if it doesn’t feel right, keep fighting for what you believe. I thank god every day that she is here with us, yes she has a issues she never had before, but it’s better than the alternative!!

    Reply
  2. Louise

    I am new to this community, as a friend of mine has AE. Diagnosed in the beginning of November 2018. We don’t know how log she had it before being diagnosed. – Somewhere between 3 and 10 months, is my guess.
    I’m interested in talking with caregivers of people who have not yet recovered.. Is there a source for this?
    Thank you, and apologies if this is an inappropriate place for this inquiry.

    Reply
  3. Amy H

    Thanks for this. You are giving me hope for my 27 yr old son who was misdiagnosed for four years and is in the ER awaiting transport to psych hospital. Indoor mold was the disease trigger for him in college apartment. He was improving with ivig then another exposure to a hurricane damaged building set him into a severe relapse. For rituxin but awaiting the benefits

    Reply
  4. Christy Follett

    My boyfriends daughter just spent a month at University hospital in Colorado with a double diagnosis
    Anti-NMDA with secondary diagnosis of arterial dissection both in front and back. She was sick for a month before anyone would listen to us that she was very sick and needed help. They had her in psych ward telling us she was crazy. We are so blessed to have checked her out and took her to another hospital where she got a correct diagnosis!

    Reply
    • Erica Snyder

      Christy, I was diagnosed and treated at UCH and then Spalding Rehab. Sorry to hear you had a bad experience! Hope your boyfriend’s daughter is now on the mend. If you need any local info or support, please let me know!! Best to you all!

      Reply
  5. Kimberly Ehmann

    As usual, I’m crying, this was an amazing piece Nesrin! Thanks Erica for this too! ❤️❤️❤️

    Reply
  6. Tina Ririnui

    My granddaughter was also diagnosed 15 months ago After going through this horrific journey from fighting to get someone to listen to being lucky enough to strike a neurologist who knew and had studied NMDARE my granddaughter at 19 is now working in the hospital and about to embark on a career as a nurse. Families need to know there is often a light at the end of the tunnel but the journey can be long with a number of unexpected turns along the way. My love goes out to all suffers of this illness and their families and friends who had to fight, hold down and make decisions that may affect the rest of their loved ones life’s when ovaries need to be removed. I like you continue to read anything and everything to try and understand why my beautiful granddaughter and all those other strangers that have gone through this and WHY!!

    Reply
  7. Deanna

    Ive been so greatful for this group Nesrin, snd for the information you have been sharing. Mydaughter still struggles with anxiety after this illness. Still so many questions and fears. One day at a time, but better knowing othersare out there.

    Reply

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