Not So Rare But Rarely Diagnosed: From Demonic Possession to Anti-NMDA Receptor Encephalitis


In 1671, 16-year-old Elizabeth Knapp was possessed by the devil.  Elizabeth served in the household of the Reverend Samuel Willard of Groton, Massachusetts, a prominent puritan Pastor, who meticulously recorded her sufferings across a four-month period.  The following passage, by Cotton Mather, a contemporary and colleague of Willard’s, based on the Reverend’s report, captures the symptoms and signs that were historically attributed to demonic procession, providing an almost clinical description of the episodes of her possession:

“…Her tongue would be for many hours together drawn like a semi-circle up to the roof of her mouth, so that no fingers applied to it could remove it. Six men were scarce able to hold her in some of her fits, but she would skip about the house yelling and howling and looking hideously…Her tongue being drawn out of her mouth to an extraordinary length, a daemon began manifestly to speak to her; for many words were distinctly uttered, wherein are the labial letters, without any motion of her lips at all; words also were uttered from her throat, sometimes when her mouth was wholly shut, and sometimes when her mouth was wide open, but no organs of speech were used therein. The chief things that the daemon spoke were horrid railings against the godly minister of the town; but sometimes, likewise, she belched out most nefandous [sic] blasphemies against the God of Heaven.” (Mather, pg 391)

The demon-possessed have fascinated and terrified populations wherever they have made an appearance. This fascination is reflected in the volume of historical accounts referencing the behaviors of the possessed, and the number of attempts at characterizing the signs of the devil which include Cotton Mather’s Magnalia Christi Americana, the Rituale Romanum or Roman Ritual, the Catholic church’s official guide to the rites and rituals that are performed by Catholic priests, or the Malleus Maleficarum from 1486 by Heinrich Kramer, a treatise, on the identification and prosecution of witches.   Throughout the ages, convulsions, contortions of the body and face, including the tongue, super-human strength, catatonic periods, long periods of wakefulness or sleep, insensitivity to pain, speaking in tongues, and a predilection for self-injurious behaviours have all been offered as physical evidence of possession.

This fascination continues in contemporary times, as evidenced by the success of many horror films, including The Exorcist (1973)—a dramatized thriller loosely based on the 1940’s documented account of a 13-year-old boy from St. Louis, Missouri, who was allegedly possessed by the devil—and media-based accounts of new cases. The modern day interpretation, however, comes with a plot twist befitting a media spectacle.

There is growing consensus in the medical community that many prior accounts of “demonic possession” may have represented original accounts of what is now broadly known as “autoimmune encephalitis”. This term unifies a broad number of autoimmune diseases, which all result in severe symptomatic brain inflammation owing to an antibody-mediated attack on central nervous system tissues that is sufficient to account for the clinical presentation. Perhaps the best understood medical surrogate for demonic possession is the recently characterized diagnosis of anti-NMDA receptor encephalitis (NMDARE). To the patient or their loved ones, it is a malady like no other, characterized by the rapid onset of symptoms so fierce and so encompassing, that the patient is often described “as if possessed”.

The first diagnosed case of NMDARE in Canada occurred in a 12-year-old girl seen at the Children’s Hospital of Eastern Ontario (Ottawa, Ontario) in 2008. Symptoms began insidiously with memory loss following a flu-like illness. The child would ask a question of her mother, and then following an explanation, would ask it again.   Routine blood tests and neurological testing in the local emergency department were unrevealing; the symptoms were attributed to anxiety and the patient was discharged to the care of her general practitioner. 

Within days of evaluation, however, the nature of the illness changed. The child started exhibiting delusional behavior— speaking about herself in the third person while being assessed by her general practitioner—and suffered a dramatic change in behavior. While stopped in traffic, en route to the hospital to be reassessed, the child calmly undid her seatbelt, leapt from the car and started pursuing a city bus—as if possessed.   When not allowed to board, she became aggressive, kicking and yelling obscenities: “blasphemies against the God of Heaven”, and all others in the vicinity. An ambulance was called, and the girl admitted to hospital. Six weeks of psychiatric and neurological assessment yielded no diagnosis until a single test performed on cerebrospinal fluid returned positive. The discovery of circulating autoantibodies directed against the GluN1 receptor subunit of central nervous system NMDA receptors confirmed the diagnosis of NMDARE, providing a medical diagnosis for the ethereal transformation witnessed by family.

As this case illustrates, NMDARE most often begins innocuously with flu-like symptoms that may serve to increase the permeability of the blood-brain barrier, allowing antibodies in the blood to penetrate to the privileged central nervous system, setting the stage for the main event. Over the following days or weeks, the transformation is unmistakable. Psychiatric symptoms predominate, characterized by delusions; hallucinations; extreme agitation; confused thinking; disinhibited behaviours, such as hypersexuality or hyper-religiosity.  During this phase of the illness, most patients require admission to hospital and implementation of chemical or physical restraints.  A further decline is heralded by the appearance of neurological signs:  seizures, memory loss, loss of coherent speech, loss of mobility, ocular deviations, catatonia, the absence of sleep, lasting for days, weeks or even months and involuntary movements. 

The abnormal movements attributed to NMDAR encephalitis closely overlap with those previously attributed to demonic possession, with a focus on perioral and peri lingual disturbances, which are often complicated by severe disturbances or disruptions in autonomic functions of breathing, heartbeat, and blood pressure. The most severely affected patients are often rendered unconscious—either as a consequence of disease or of sedative medications required to manage intractable seizures, movement disorders or autonomic fluctuations. Supportive measures including ventilation, cardiac pacing, and supplemental feeding may be required for weeks, months, or in the most severe cases, years.  

Considering the spectrum of terrifying symptoms, it is understandable why in earlier times they may have been attributed to demonic possession. It is equally comprehensible why many contemporary patients are initially admitted under psychiatry, with diagnostic considerations spanning the pages of the Diagnostic Statistical Manual of Psychiatry. Only recently, has a diagnostic test become available. The syndrome of NMDAR encephalitis is owed to the end- effects of a circulating autoantibody. As with most autoimmune diseases, NMDARE is more commonly described in younger females (approximately 80% of cases), but has been identified in males and females, from infancy to 85 years.  In many patients, the disease is frequently associated with a hidden secret:  a “monster” within.  

Tumours of the ovaries are described in 60% of women of childbearing age. In most cases, these tumours consist of primitive cells, with the potential to differentiate into any tissue in the body, including hair and teeth, or even brain tissues. The fantastic appearance of these tumours earned them the designation of “teratomas”, derived from the Greek, teraton, meaning ‘monster.’ Inclusion of brain tissue within disease-associated teratomas may be especially important to the development of NMDARE. In these patients, it appears as though antibodies are produced against tumour cells containing NMDA-receptors, which then cross-react with native brain tissue accounting for the clinical presentation of NMDARE. In patients with teratoma-associated ANMDARE, identification of the tumour using magnetic resonance imaging (MRI), computerized tomography (CT scan) or ultrasound (US), is critical for the outcome of the patient, with removal of the teratoma heralding recovery in most cases. Tragically however, this is not always the case.  In the subset of patients with disease not associated with an underlying tumour, in whom the trigger for this illness has yet to be identified, poor outcomes and /or susceptibility to relapses may be more common.  Six percent of patients diagnosed with ANMDARE die or are left with severe and permanent consequences of their illness.

Although antibodies against the NMDARE were first identified in 2007 by Dr. Josep Dalmau, a professor of neurology and oncology at the University of Pennsylvania, clinical cases compatible with a diagnosis of NMDARE abound in the medical literature. One of the best described cases was reported in 1999 by Canadian doctors involved in the treatment of a 24-year-old Chinese female patient at Toronto Western Hospital. In the article, the author’s report her presentation as a reversible paraneoplastic encephalomyelitis associated with a benign ovarian teratoma.  A diagnosis of NMDARE was retrospectively confirmed in 2007.   By 2011, the number of positively diagnosed cases in Canada had jumped to 22 (data courtesy Dr. J. Dalmau). Since then, the number has tripled and quadrupled as more and more cases are now being recognized and treated.  According to Drs. Day and Peery of The Anti-NMDA Receptor Encephalitis Foundation in Canada, the disease is no longer as rare as previously thought, but rather “a rare diagnosis.” (Day and Peery, pg. 90) 

With a dire lack of awareness on the part of many physicians, patients are still being incorrectly diagnosed, opening up the possibility of unnecessary internment in psychiatric and/or acute- care facilities, and delaying access to necessary treatment.  Since the first descriptions of this illness, university-affiliated hospitals across Canada (including hospitals affiliated with the Universities of Calgary, McMaster, Ottawa, Montreal, and Toronto), have amassed considerable expertise in the diagnosis and management of NMDARE. They are well-equipped to manage the wide-ranging and unpredictable symptoms and sequelae associated with this illness, contributing to a medical literature filled with stories of near-miraculous recovery in affected patients receiving an expedited diagnosis and aggressive treatment, with immune suppressing and/or modulating medications.

One such extraordinary recovery was documented by Susannah Cahalan, a journalist for the New York Post, in her award-winning article, My Mysterious lost month of Madness, (NY Post, 4 October 2009). Three years later, building on the foundations of her article, she wrote the best-selling book, Brain on Fire: My Month of Madness (Simon and Schuster, 2012). The book has served to raise the profile of NMDARE, providing much needed momentum for patients, families, clinicians and researchers who are battling NMDARE and related forms of autoimmune brain disease.  

The film based on the memoir will premiere at the 2016 Toronto International Film Festival, September 8-18.  In the social media circuit, innumerable support groups have arisen. Facebook support groups and pages dedicated to the topic have been established in 9 countries (and growing), and registered Foundations committed to advancing research, education and support in this disease are beginning to take shape. On this front, Canada is leading the way with the incorporation of The Anti-NMDA Receptor Encephalitis Foundation in 2012 ( and its recognition as a tax-deductible charitable foundation by the Canadian Revenue Agency (CRA) in 2013.

The storied history that led to the discovery of NMDARE is filled with travelers once thought to be demonically possessed or bewitched , paying the ultimate price of misdiagnosis by being wrongly accused, convicted and sentenced to torture and death.  With recent discoveries, hope for quicker diagnosis and therapies continues unabated. Those who have teetered on the edge of the abyss because of an incorrect diagnosis are being brought back and will continue to be brought back. Although there are remarkable reports of recoveries that happen relatively quickly, there is continuing need for greater awareness, expedited treatment, and support for those caught directly or indirectly in the path of this illness.  There may never be a cure, but thanks to recent scientific advances, a disease once characterized as “demonic possession” has a new name, and those on the dark journey from illness to health have reason to hope and to fight on.


The author wishes to thank co-founders, of the Anti-NMDA Receptor Encephalitis Foundation, Inc, Dr. G. Day, Dr. W. Foster and Dr. H. Peery for their invaluable input and guidance in the writing of this article.



(1) Cotton, Mather, Magnalia Christi Americana, 1st American,1820, Roberts & Burr, Printers in Hartford: Published by Silas Andrus, Google Books, pg. 391

(2) 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.

(3) Day, Gregory S, High, Sasha M.,, Anti-NMDA-Receptor Encephalitis: Case Report and Literature, JGM, February 12, 2011

(4) Sébire, Guillaume, In Search of Lost Time: From “Demonic Possession” to Anti–N-Methyl-DAspartate Receptor Encephalitis. Annals of Neurology, Volume 67, No. 1, pg 141-142.

(5) Blaine, R., et. al., Reversible Paraneoplastic Enephalomyelitis Associated with a Benign Ovarian Teratoma., Canadian Journal of Neurological Sciences, Volume 26, no. 4, November 1999, pg 317-320.

(6) Hammer, C., Neuropsychiatric disease relevance of circulating anti-NMDA receptor autoantibodies depends on blood–brain barrier integrity. Molecular Psychiatry, 2013, pg 1-7.

(7) 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.



  1. Fascinating article, thank you for sharing this. This is such an interesting topic to me because it reflects the beliefs and general perspective of a culture, and the stories that occur around it to give context to bizarre experiences.

    I know that some cultures believe that *all* illness is the result of influence from dense energy taken on from the collective by an individual, as per having poor or no defenses and boundaries. And here, we are learning the converse belief, that illness is what creates the illusion of dense energy infiltration. Kind of a chicken and egg thing.

    In any event, I think what’s important is exactly what you say, to focus on whatever gives hope and encouragement to heal. That’s how a healing path is illuminated, from hope and courage.

    Wishing you the very best with your research around all of this. I think it’s a rich and relevant topic. And good healing to your daughter.

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    • About loss of boundaries, taking on others’ energies: I experienced this as a side effect (somebody suggest a better term- oldhead? Frank? help me out here) of the drug Effexor. I basically could not maintain energy shields that, as an energy empath, I rely on. Without that drug in my system, energy maintenance was something I kind of just did throughout the day without really thinking about it. But under influence of Effexor, I constantly felt misunderstood by and in conflict with the people in my life. I did not recognize that my ability to shield had been compromised to the point of not being able to distinguish my own emotions and energies from those of people around me. It was only after withdrawal (vertigo from hell!) that I came to understand what I had been experiencing.

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      • Ditto, exactly. I just made a post on the Gut article “in the news” regarding how psych drugs disconnect us from our grounding, too. So one is ungrounded and with boundaries/defenses compromised on the psych drugs. In other words, people are rendered powerless, in that they lose access to our own energy and the daily maintenance of it–vital for well-being–and as a result, live a life of dependence and the underlying fear that accompanies this, rather than self-agency, which inspires freedom and confidence. Really great point about energy shields, LavenderSage.

        This all relates to what I say above about cultural beliefs, and the stories we create around experiences outside the norm. From those stories, we create our reality, if that is what we are believing and projecting–then we are creating it. Stories of demonic possession will create a reality of this, for examples. Stories of chronic illness will create this, as well. Stories of healing through a process of energy transmutation will, in turn, create that particular reality. It’s all in what we can allow ourselves to believe.

        Personally, I put everything in terms of energy, and my perception is based on what feels easiest and lightest in my body. I can pretty much boil everything down to grounding, boundaries, and centeredness–that is, knowing one’s higher self neutrality, no judgment and broadest perspective. When we understand how our energy works, we can create any story–and therefore, any reality–we choose. Hopefully, one that is uplifting, and not damning. We have the capacity to do either, based on where we choose to focus and what energy we project onto any experience, whether ours or that of another.

        Yet another component in the reality we create for ourselves–what are our stories and what is the quality of our energy? Those are all choices we make every day.

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        • I found the psych drugs to affect grounding, energy seemingly from the collective unconscious, boundaries, also. When I was on the drugs, I had the incessant ‘voices’ of the evil people who abused my children in my head. It was as if the drugs took away my ability to have peace of mind and autonomy. Then, as I was weaned off the drugs, it was as if the good within the collective unconscious came to help save me, they started supposedly harassing the evil ‘voices.’ And I do recall one of the real life child abusers curled up on the basement floor of a church, looking anguished at that point in time, as if she were really being harassed.

          And then during the drug withdrawal induced manic phases, wow, talk about excessive energy and staggering synchronicity. I had perfect strangers coming up to me and talking to me about my private thoughts, a pastor told me “some people can’t pray in private,” numerous people commented on how they could “feel the power,” and the seeming energy also ruined a cell phone and hotel key cards. The music lyrics on the radio seemingly coordinated with my thoughts and concerns, as well as with the vanity plates of people’s cars I drove by during my seeming spiritual journey. It was like a giant battle of good vs evil was taking place within the collective unconscious, but it was seeping into the waking reality, too.

          I do agree with Alex that this energy can be used to create for one’s self a positive story, especially if one remembers good does triumph over evil in the end. And I know people can heal from such extreme states. I wish you well, Nesrin, and will pray for your daughter’s full recovery. Thank you for sharing your story, and keep believing.

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  2. Thank you so much, Nesrin, for sharing this vital information and thanks to MIA for giving you the space to do it. And kudos to the scientist who solved this particular mystery. It is worth recalling that multiple sclerosis, another autoimmune condition, used to be known as “hysterical paralysis.” And, lupus, a decidedly autoimmune illness, quite often presents psychiatric symptoms.

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    • @dave_cm thanks for providing the link to this terrific article in the Atlantic. There are cases of autoimmune encephalitis for which an antibody has yet to be identified, such as the one described in the article. New antibodies ccontinue to be identified, however anti-NMDA is the most commonly identified one. A statistic which I neglected to include is that approximately 40% of cases are pediatric.

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  3. I bet one of these guys just got busted down in Florida, after going on a rampage, smashing up a number of cars and killing two people by beating them to death. It took multiple cops with tasers and a police dog to subdue him. Afterwards he mentioned something about periodically feeling or being “possessed” on occasion. Question: will anyone down there bother to take a sample of his cerebrospinal fluid to look for undesirable antibodies?

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      • “… I hope to see the day where all first episodes of psychosis will be tested.”

        This should become standard rule-out protocol. But is this condition invariably acute, or can it also manifest itself as a lower-grade, chronic inflammation that presents the symptoms less dramatic ways? This, I think, would make the condition more likely to be psychiatrized. Do you see any value of a regimen of anti-inflammatory supplements, either prophylatically or as part of one’s maintenance protocol? We inhabit a pro-inflammation world…stress is inflammatory, our diets are inflammatory, toxins in the environment are inflammatory, but not every succumbs. Is it known what predisposes people to this—e.g., a more permeable blood-brain barrier in case the antibodies originate outside the brain (do they?)? Inability to detoxify?

        I want to thank you again for this incredible contribution to our body of knowledge. All the best to your daughter and you.

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        • @GetItRight, Firstly, thank you for the good wishes. Today in fact my daughter started college; a chapter in her life which I was not sure we would see. To answer your question of whether this condition can “manifest itself as a lower-grade, chronic inflammation that presents the symptoms less dramatic ways?” It does indeed! In the largest study to-date of 577 cases, approx 1% of these cases manifested with predominantley psychiatric symptoms. They were lucky to have been identified and to have received life saving treatment. Who knows how many others are out there though, that are not so fortunate with unthinkable consequences.
          Do I see “any value of a regimen of anti-inflammatory supplements, either prophylatically or as part of one’s maintenance protocol?” Yes, why not. A leaky blood brain barrier has been postulated by C. Hammer,, in the article entitled Neuropsychiatric disease relevance of circulating anti-NMDA
          receptor autoantibodies depends on blood–brain barrier integrity in Molecular Psychiatry advance online publication, 3 September 2013; doi:10.1038/mp.2013.110, in case you are interested in reading it.
          Thank you for your interest and for asking so many pertinent questions.

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          • Thank you so much, again, Nesrin. Can you provide your contact information for those who are interested in testing or more information? I would also like to make this information available to my daughter’s doctor who is uncommonly intelligent, open-minded and eager to learn. Thank you again.

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          • @GetItRight I can be contacted via at the email [email protected].

            You will find much useful information on the website, including a collection of medical literature, patient stories, as well as a listing of labs that test, in US, Canada and Europe.

            Many doctors still don’t know, or think they know. Unless the patient presents with the classic presentation of flu-like prodrome, psychiatric symptoms, hyperkinetic phase and then commatose or complete coma, which happens over a period of days or weeks, others who have predominantly psychiatric presentation may not get the testing they need.

            What we need are curious and interested physicians and ones like your daughter’s GP who are open to learning new things.

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    • “People diagnosed with schizophrenia often report that they never developed childhood illnesses, even being impervious to the common cold.”


      this correlates with 1 biotype of schizophrenia, the low-histamine, overmethylated individual who has no inhalant allergies. The following is from Linus Pauling’s
      Orthomolecular Psychiatry on the low histamine child:

      “The patient is a hyperactive….child who is unnaturally healthy. For example, the rest of the family may get head colds, but this low histamine child misses the cold or the virus infection fails to produce a rhinitis. He is hypo-allergic..he may show no signs of pain even when seriously bruised or when a venous blood sample is obtained….The child is constantly active and sleeps poorly. His attention span is short so learning is poor. Although his ability in some areas may be high when tested, a high degree of disperceptions may be present, such as sensory, time, body, self, and perception of others.”

      This is in contrast to the regressive biotype, involving undermethylation/high histamine, where the break happens after great functioning up to that point. According to Dr. William Walsh (of Nutrient Power), the psychotic manifestations of the overmethylated biotype are mostly sensory (hallucinations, hearing voices), whereas thought disorders (delusions) predominate in the regressive, undermethylated biotype.

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      • Thanks for the additional information. “Schizophrenia” is so confusing. As a parent, with anecdotal knowledge of only my son, I don’t think any researcher, including William Walsh, has got it right. People present with symptoms that are wildly disparate. I was thinking of Abram Hoffer when I made this remark. He said it in a general sense, that parents report that their children tended to be abnormally healthy in childhood. My son was that way. I also used to remark that my mother, who developed dementia in her later life, was also abnormally healthy. I’m hopeful that, perhaps for the first time, science is headed in the right direction. But, I’m not holding my breath.

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  4. ” I don’t think any researcher, including William Walsh, has got it right.” I agree that no one has THE answer or the full solution. A number of people (Dr. Walsh, Dr. Natasha Campbell-McBride, Dr. Perlmutter) have advanced the body of knowledge, but thus far no one has brought us to the Promised Land. I am cautiously optimistic about the inflammation/immune system angle, though, because the dots to be connected are starting to line up. For example, the fact that a physical, autoimmune condition such as lupus can morph into psychiatric disturbance (Lupus Cerebridis) when the inflammation reaches the brain. The fact that people often benefit from non-inflammatory, or better yet, anti-inflammatory diet (e.g., gluten free). The fact that psych meds, however horrid, do have some anti-inflammatory properties which may explain why they subdue symptoms. Until science (i.e., not psychiatry) finds the answer, I wonder how a regimen of non-drug anti-inflammatory supplements might work.

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    • Megadose niacin is also an anti-inflammatory, thanks in large part to the work of Hoffer and Osmond. It’s good in so many respects, but not a magic bullet for “mental illness,” in my experience. That being said, many people claim that they have recovered on the Hoffer/Osmond protocol. I, too, am cautiously optimistic that targeting the autoimmune system may produce immediate and long lasting results for more people. But, I’m prepared to be disappointed. I continue to look to all kinds of diverse healing theories and practices. So far, no one has the full answer, and maybe no one ever will, as human beings are all different. What works for one, may not work for someone else.

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      • “Megadose niacin is also an anti-inflammatory.”

        The amino acid glycine is a also powerful anti-inflammatory, in my experience. I agree with your perspective and I, too, look for different healing options and modalities. I believe that mental illness has bedeviled the “professionals” because they do not operate this way…It has not been an not a collaborative search to solve the puzzle, it has always been a contest between competing pet theories and guild interests, with too many claiming that his/her piece of the puzzle is THE answer, and it is not. For me, epigenetics has been a game changer, because it fosters a new understanding of how the environment changes biology and how profoundly everything matters.

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  5. An ex-professional footballer in England was recently tasered to death, and by all accounts, including his own family, he was deranged and dangerous prior to his death.

    It seemed at first glance to be a madman narrative. But in fact turns out to be a kidney failure narrative.

    On a personal level I had a friend with a brain tumour but did not know I had a friend with a brain tumour. He got diagnosed bipolar and busied himself adjusting to the diagnosis, then shortly after, died. During the last months of his life all the significant people in his life were adjusting to his bipolar diagnosis, and doing all they could to understand and help. In the meantime, a mutant fist was growing ever-larger in his brain.

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  6. Hi,

    I hope you’ll find this e-mail well. I’m Sidney Dagiagnao from the Philippines and currently living here in Winnipeg, Manitoba. I just would like to ask help from your organization about my friend who was hospitalized couple of days ago. The initial findings of the doctors was Autoimmune Encephalitis but because of limited facilities in the Philippines, they could not perform the tests needed to determine her sickness. Her name is Fria Grace Estrella and she is 31yrs old. Any help or information would be greatly appreciated for the sake of my friend’s life. You may contact me through my email [email protected] or phone number 204-887-6040. Thank you in advance.



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