January 12, 2022 | by Greer Prettyman, PennNeuroKnow
You might have your dad’s brown eyes or your mother’s curly hair. Traits like eye color are heritable, which means they are passed from parents to offspring. While we can inherit a lot of good traits from our parents, risk for certain diseases can also be inherited. Some diseases, like Huntington’s, are strongly linked to genetic risk factors. If someone’s parent has Huntington’s Disease, there is a 50% chance that they will develop it as well1. This is because Huntington’s disease is caused by a specific, heritable mutation in the DNA.
Not many disorders have such a clear genetic cause. However, the set of genes inherited from the parents can increase someone’s risk, or predisposition, for developing certain diseases, even if it doesn’t directly cause the disease. For example, people can have genetic predispositions for some types of cancer, psychiatric illnesses, and health risks like high cholesterol2,3,4. Recent research suggests that certain types of autoimmune encephalitis (AE) may also be linked to genetic factors that put some people at higher risk of developing this disease than others5.
Genes and Heritability
Let’s step back to understand how genetic risk is transferred from parents to offspring by taking a look at DNA. DNA is the biological material that makes us who we are. Humans and animals inherit half of their DNA from their mother and half from their father. The DNA itself is made up of four nucleotide base pairs called adenine (A), thymine (T), cytosine (C), and guanine (G). You can see in Figure 1 that the nucleotides form pairs with each other (A with T and C with G) on the two strands of the DNA double helix. The human genome has 3 billion of these nucleotide pairs6. The order of the nucleotides makes up a genetic “code” that dictates what proteins are made and eventually what traits we have. At every single position, a person can have one of these four nucleotides. Variation in the nucleotide sequence at particular locations on the DNA is what makes each individual unique. Changes of nucleotides at some positions, however, can increase risk for certain diseases.
Figure 1. Cartoon schematic of a DNA double helix with nucleotide base pairs (A,T,C, and G). At each position on the DNA, a person can inherit one of the four nucleotides and variation in the sequence produces the genetic code.
Genetic Risk for AE
Researchers can learn about genetic risk factors for specific diseases or conditions by collecting data about individuals’ genotypes. A genome-wide association study (GWAS) is used to assess the whole genomes of many people to identify genetic mutations that are associated with that disease. Researchers have conducted GWAS studies in patients with autoimmune encephalitis (AE) to search for clues about genetic predisposition5. In contrast to a GWAS study that looks at the entire genome, other genetic research focuses only on select genes that are hypothesized to relate to a disease. AE is a disorder that involves the immune system incorrectly targeting the brain’s own cells. In the case of AE, researchers often look at genes that encode proteins involved in the immune system, which are likely locations for genetic mutations that might increase risk for this disease.
It turns out that some types of AE, like limbic encephalitis, are more closely tied to genetic risk factors than others7. The main genetic factor that has been associated with limbic encephalitis is called human leukocyte antigen (HLA). HLA genes are found on chromosome 6 and are categorized into three classes, class I, II, and III, which have genes that encode different proteins that help to regulate the immune system7. Mutations in these genes have been associated with a variety of disorders that involve autoantibodies, including limbic encephalitis7.
The most common form of limbic encephalitis that is not caused by cancer involves anti-leucine-rich glioma-inactivated 1 (anti-LGI1) antibodies7. Anti-LGI1 limbic encephalitis is associated with a mutation in part of the class II HLA gene complex. Anti-LGI1 antibodies are in the IgG4 isotype, which has been associated with HLA genes in a variety of autoimmune conditions7,8. A genetic mutation called DRB1*07:01 was found to be carried in up to 90% of people with anti-LGI1 encephalitis9. This suggests that this specific HLA mutation is associated with the development of limbic encephalitis, although the exact biological mechanisms are still unknown7.
In contrast to anti-LGI1 limbic encephalitis, anti-NMDAR encephalitis has not been found to have a strong relationship to HLA mutations7. A GWAS study found evidence for some weak links with HLA mutations, but there were no genetic mutations common to both anti-LGI1 limbic encephalitis and anti-NMDAR encephalitis5. Anti-NMDAR encephalitis is caused by antibodies of the IgG1 isotype, which may explain why there is a weaker association with genetic variations in HLA, which are more strongly associated with the IgG4 isotype7. One study did find differences in genes that encode inflammatory cytokines related to anti-NMDAR encephalitis in a small Southern Han Chinese population10, but more research is needed to determine if this association holds true in other populations.
The heterogeneous nature of AE makes it hard to pinpoint exact genetic risk factors. It is clear, however, that the interaction between a person’s genes and their environment is a stronger predictor of whether they will experience a particular outcome than genetics alone. For example, environmental factors like contracting a virus can lead to AE. Someone with a genetic predisposition may be more likely to get AE after a virus than someone without those genetic mutations. Although researchers have learned that individuals with particular mutations in HLA genes are likely at greater risk for developing limbic encephalitis, more work will be needed to understand the biological mechanisms and links with environmental risks that lead to AE. Ultimately, the goal would be to use what we can learn about a person’s genetic risks to predict and prevent AE.
References:
Caron NS, Wright GEB, Hayden MR. Huntington Disease. 1998 Oct 23 [updated 2020 Jun 11]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Mirzaa G, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2021. PMID: 20301482.
Garber JE, Offit K. (2005). Hereditary cancer predisposition syndromes. J Clin Oncol. 23(2):276-92.
Baselmans BML, Yengo L, van Rheenen W, Wray NR. (2021). Risk in Relatives, Heritability, SNP-Based Heritability, and Genetic Correlations in Psychiatric Disorders: A Review. Biol Psychiatry. 89(1):11-19.
Bouhairie VE, Goldberg AC. (2015). Familial hypercholesterolemia. Cardiol Clin. 33(2):169-79.
Mueller SH, Färber A, Prüss H, Melzer N, Golombeck KS, Kümpfel T, Thaler F, Elisak M, Lewerenz J, Kaufmann M, Sühs KW, Ringelstein M, Kellinghaus C, Bien CG, Kraft A, Zettl UK, Ehrlich S, Handreka R, Rostásy K, Then Bergh F, Faiss JH, Lieb W, Franke A, Kuhlenbäumer G, Wandinger KP, Leypoldt F; German Network for Research on Autoimmune Encephalitis (GENERATE). (2018) Genetic predisposition in anti-LGI1 and anti-NMDA receptor encephalitis. Ann Neuro. 83(4):863-869.
National Research Council (US) Committee in Mapping and Sequencing the Human Genome. Mapping and Sequencing the Human Genome. Washington (DC): National Academies Press (US); 1988. 2, Introduction. Available from: https://www.ncbi.nlm.nih.gov/books/NBK218247/
Muñiz-Castrillo, S., Vogrig, A., & Honnorat, J. (2020). Associations between HLA and autoimmune neurological diseases with autoantibodies. Auto- immunity highlights, 11(1), 2.
Koneczny, I., Yilmaz, V., Lazaridis, K., Tzartos, J., Lenz, T. L., Tzartos, S., Tüzün, E., & Leypoldt, F. (2021). Common Denominators in the Immunobiology of IgG4 Autoimmune Diseases: What Do Glomerulonephritis, Pemphigus Vulgaris, Myasthenia Gravis, Thrombotic Thrombocytopenic Purpura and Autoimmune Encephalitis Have in Common?. Frontiers in immunology, 11, 605214.
Vogrig, A., Muñiz-Castrillo, S., Desestret, V., Joubert, B., & Honnorat, J. (2020). Pathophysiology of paraneoplastic and autoimmune encephalitis: genes, infections, and checkpoint inhibitors. Therapeutic advances in neurological disorders, 13, 1756286420932797.
Li X, Zhu J, Peng Y, Guan H, Chen J, Wang Z, Zheng D, Cheng N, Wang H. (2020). Association of Polymorphisms in Inflammatory Cytokines Encoding Genes With Anti-N-methyl-D-Aspartate Receptor Encephalitis in the Southern Han Chinese. Front Neurol.
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Become an Advocate by sharing your story. It may result in accurate diagnosis for someone suffering right now who is yet to be correctly identified. Submit your story with two photos to IAES@autoimmune-encephalitis.org
International Autoimmune Encephalitis Society (IAES), home of the AEWarrior®, is the only Family/Patient-centered organization that assists members from getting a diagnosis through to recovery and the many challenges experienced in their journey. Your donations are greatly appreciated and are the direct result of IAES’ ability to develop the first product in the world to address the needs of patients, Autoimmune Encephalitis Trivia Playing Cards. Every dollar raised allows us to raise awareness and personally help Patients, Families, and Caregivers through their Journey with AE to ensure that the best outcomes can be reached. Your contribution to our mission will help save lives and improve the quality of life for those impacted by AE. For this interested in face masks, clothing, mugs, and other merchandise, check out our AE Warrior Store! This online shop was born out of the desire for the AE patient to express their personal pride in fighting such a traumatic disease and the natural desire to spread awareness. Join our AE family and help us continue our mission to support patients, families and caregivers while they walk this difficult journey.
FREE Webinar Series. Open to the public. Register Now to secure your space as seating is limited. IAES has arranged for some of the top experts in the field of autoimmune neurology and psychiatry to make presentations structured specifically for the layperson in mind on the most commonly asked about topics. Encourage, friends, family members, as well as your doctors and therapists, to attend one or more of these presentations.
2.
Autoimmune Encephalitis Trivia Playing Cards
Autoimmune Encephalitis Trivia Playing Cards
Purchase decks for your family members, friends, doctors and therapists during AE awareness month. IAES in collaboration with Dr. Josep Dalmau has created the first product in the world specifically addressing the needs of the AE Warrior™ and those impacted by Autoimmune Encephalitis. ALL proceeds will support Dr. Dalmau’s research group. Our excitement continues to build over the rave reviews we are receiving from experts in the field about our AE Trivia playing cards. Doctors have begun to provide decks to their patients and have been receiving smiles all around.The support patients have been reporting is so exciting and gratifying to hear. This simple educational and rehabilitation tool appears destined to be the greatest personal support any AE patient, caregiver, therapist, teacher, or medical professional can own. A true game-changer in helping you to become a strong advocate, receive an outstanding educational foundation about AE, and doubles as a rehabilitation tool!
Watch and Share our Awareness video AE Warriors Stepping Forward
This is My Time
This inspiring video shows the wide age range and diversity of AE patients, it explains what AE is in simple terms and provides key RED FLAG warnings to any medical professional who views it. This is IAES’s 5th annual awareness video. Sharing this video on your social media platforms has proven to have a profound impact in raising AE awareness among the medical community and public which has lead to many patients receiving an accurate diagnosis in past years.
4.
Get your Story in your Local Newspaper or Television Station
Get Your AE Story in the News
IAES has done the work for you. Download our press release and directions. Reporters can make use of the quotes from experts cited in the press release to enhance any article. Additionally, you can provide any writer with the contact information for the doctor who diagnosed you. Make sure you contact your doctor to confirm that they would be open to discuss your case with a reporter for a human interest or health story. Personal stories about AE patients and their journey are the best way to raise awareness broadly and on a much larger scale. It involves a few simple steps. Contact local and national newspapers as well as popular magazines such as People, Time and Newsweek.
5.
Hold a FUNdraiser or Awareness Event at Work, School or Your Home
This is your month to shine a light on Autoimmune Encephalitis. The IAES FUNdraiser Pageprovides several ideas for advocates of all ages to raises AE awareness. Support the vital work IAES does for the international AE community and have FUN at the same time. Warrior on AE Warrior! Let’s create the change we want to see in the world together.
Spread awareness with these stylish, 2-sided designed shirts. Shirts may be ordered in Men’s, Women’s, and Children’s sizes. There are a variety of styles and colors including long sleeves and hoodies to choose from. Wearing this shirt may begin a conversation that could lead to saving a life. The proceeds of your purchase will immediately support autoimmune encephalitis patients, caregivers, and families who are walking this difficult journey. Proceeds also go to support research that may one day lead to a cure. Front Description: Autoimmune Encephalitis Awareness Month, February 2021. Back reads: Autoimmune Encephalitis (AE): is a type of brain inflammation where the body’s immune system attacks healthy brain cells.
6.
Assemble AE Survival Kits
Share your love and encouragement by purchasing a survival kit, (Goodies not included). IAES has created 11 different variations of these kits that are bound to bring smiles of pleasure to those who receive them. Create a kit for your AEWarrior™, AE Mom, Doctor, Psychiatrist, Nurse, Infusion day, Child or Caregiver. These kits are available year-round.
7.
Raise Awareness with IAES Candy Bar Wrappers
IAES has created 14 unique candy bar wrappers you can raise some sweet awareness. These free wrappers include sentiments for people in the AE community and public. These wrappers can be given as your simple act of kindness or used as a fundraising vehicle. They are a wonderful way for children and siblings to get involved in fundraising and raising awareness as well. Candy wrappers will be available throughout the year.
8.
AE Warrior and AE Caregiver Royal Registry Certificates
The Royal IAES Registry designates The AE Warrior™ and AE Sentinel with Royal Title. In recognition of their heroism under fire. The Royal IAES Registry is the highest honor to be bestowed upon those engaged in the mighty autoimmune encephalitis battle. Without warning and within an instant, these unprepared citizens were thrust unto a perilous fire raging battlefield. To fight demanded that they dig deep into the depths of their soul for the inner-strength they had to summon to save their life or the life of the one they loved. This act is so rare IAES sanctifies and affirms by sealed decry the bestowing of Royal Title into the IAES Registry on the second month of each year.
9.
The IAES Virtual Art Show
Tour the IAES Virtual Art Show and be ready to feel touched by the work expressed in this very special show. Share the link on your social media platforms. Art in a variety of forms done by AE patients, family members, and caregivers of all ages is showcased. Experience insight into Autoimmune Encephalitis through their eyes. It is a moving experience and one we are honored to give you.
10.
Become an IAES Angel and receive a facebook picture frame announcing that you have
The IAES Angel has lifted IAES upward by ensuring that comfort, guidance and improved health is brought into an AE patient’s life. IAES Angels are motivated by their Spirit of giving. They are Champions in raising AE awareness.When you become an #IAESANGEL,International Autoimmune Encephalitis Society will send you this badge and profile frame to place on your Facebook page or Website. As badges ‘take flight’ heralding IAES has been ‘touched by an angel’, others will take notice and they too may find their wings. Together, we will create a future where AE is eradicated from this world and only referenced in medical history books.
11.
Print and share this AE Infographic
Post this Infographic throughout the month on your social media platforms and also download it onto card stock paper and give it out at school, work, gym or your place of worship.
My dad and my brain go back more than a few decades. When I was two, he convinced my eldest sister she could teach me to read, which I insisted upon in order to move on from coloring books. It wasn’t that I was bored with Dad reading Dr. Seuss to us before bed, it was a fascination with the stories that I wanted MORE.
Among my rather large family—including more than a dozen cousins, with whom our young parents raised more like a collective of siblings—I was given the nickname “The Brain.” I took no offense at the name (until adolescence finally kicked in); rather, I relished reading in a corner when the rest were doing anything else.
It paid off, too. I was immediately admitted to the public school’s advanced program, while my four siblings attended the local parochial school. Dad generally drove us to school and I was the final drop-off, during which time he encouraged my academic achievement in multiple ways, whether quizzing me on spelling words or asking me to solve math problems in my head.
Dad was in advertising, heavily involved in political campaigns, which also set the stage for my career in public relations and marketing—including a stint as a registered lobbyist for the Health Insurance Association of America. As a matter of course, the last three people who hired me asked in the interviews whether I was his daughter. My answer weighed heavily in my favor.
Fast-forward to November 2018… During dinner with my boyfriend, I said something so out of course with our conversation, that Tim was stunned. The next day I had no recollection of it and he insisted I see my internist, who knows me well enough that I was sent immediately for an MRI. Limbic encephalitis was rampant and the obvious diagnosis. (I’ve had epilepsy for nearly 30 years, due to an entirely separate and resolved diagnosis, so all seizure activity was well-controlled, making my memory issues the trigger in my case.)
Upon receiving this new diagnosis, I communicated it to my family. My sister, Suzanne (the one who taught me to read), is now a bioethicist in Washington state, and she arranged for me to be seen at Mayo Clinic for a consult with Dr. Sean Pittock, who agreed out of professional courtesy. Immediately upon meeting me during my office visit, he admitted me and began my steroid treatment.
During this time and since, Suzanne, Dad and I have been in daily text communication. Sometimes it’s related to my encephalitis, though often it’s about our beloved University of Louisville Cardinals, the Chicago Cubs, Thoroughbred racing, or the political antics of the moment. Never has Dad wavered in his commitment to my wellness.
Once it became apparent that working at a job I once loved was no longer possible because of my significant memory issues, he has continued to nudge me along intellectually. He’s convinced “The Brain” will overcome and achieve in new ways. There are days I’m not yet there with his belief, but more often than not, I’m still the kid who’s being quizzed in the car on the way to school. Happy Father’s Day, Dad!
Terry Holland
She Didn’t Stand Alone, She Had Her Father
June-21-2020 | Mari Wagner Davis
She did not stand alone, but who stood behind her, the most potent moral force of her life was the love of her father. Harper Lee.
Father’s Day is a day we celebrate our fathers. We may take them out to dinner, send a card, or make a special phone call. There have likely been times when we have argued or butted heads with our fathers. Times when they have come to our rescue. Times when they have chewed us out for doing something goofy. I didn’t really realize how important my parents, my father is, in my life until I had seizures and was diagnosed with autoimmune encephalitis.
Growing up, my Father’s goal was to make sure we were competent, independent adults. We had to learn to read a map, change our oil, when we were five he helped us open our own bank accounts and made sure we put money in them to save. One thing he couldn’t protect me from or prepare me for was autoimmune encephalitis. But as always, my parents have stood behind me, loving me, supporting me, at times holding me when I cried from the frustration of not being who I was before and celebrating the small goals I have achieved as I have inched along in my recovery.
Events one doesn’t conceive of celebrating such as when I completed day rehab, passed my special driving test so I could resume driving, and when I was able to stay up all day without a nap. (Autoimmune encephalitis makes you celebrate the small things).my Father celebrated with me.
So, when we feel alone, know that whether we still have our Fathers physically with us or not, they stand behind us, cheering us on.
Happy Father’s Day DadWillard Wagner
Become an Advocate by sharing your story. It may result in someone receiving an accurate diagnosis who is suffering right now and is yet to be correctly identified. Submit your story with two photos to IAES@autoimmune-encephalitis.org
International Autoimmune Encephalitis Society (IAES), home of the AEWarrior®, is the only Family/Patient-centered organization that assists members from getting a diagnosis through to recovery and the many challenges experienced in their journey. Your donations are greatly appreciated and are the direct result of IAES’s ability to develop the first product in the world to address the needs of patients, Autoimmune Encephalitis Trivia Playing Cards. Every dollar raised allows us to raise awareness and personally help Patients, Families, and Caregivers through their Journey with AE to ensure that the best outcomes can be reached. Your contribution to our mission will help save lives and improve the quality of life for those impacted by AE.
The last two years of my life seem to have disappeared from my memory. Gone. Holidays, weddings, a funeral, birthday parties, Christmas and New Year. Friends and family keep telling me things I’ve done and the way I’ve behaved, some of which are very embarrassing to hear. It’s just not me.
This is the result of the disease Autoimmune Encephalitis (AE), the symptoms of which I was clearly exhibiting without my even realizing. Hallucinations, involuntary movements (which developed to 20-30 movements over four or five minutes), insomnia, loss of inhibition, memory loss and finally seizures, none of which I can remember. Apparently, I had two massive seizures at work (a Secondary School where I teach Physical Education), one of which resulted in the police being called due to my resisting all help. I’m told this was the last of a number of smaller seizures as the disease continued to develop and take hold.
The last seizure resulted in hospitalization for more than two months and being seen by a number of doctors and specialists who put me through a whole host of MRI scans, EEG’s, blood plasma analysis and other tests I don’t recall. I was eventually transferred to another hospital, where a specialist identified AE straight away, where I stayed and was treated for more than three weeks.
Lots of my friends and family traveled to see me, none of which I can remember and feel very guilty about admitting to. I do have a memory of very small flashes of shouting inappropriate comments at some female staff and having to apologize the next day and some very small flashes of walking around on other wards in my underwear looking for my ward. Again, it’s very embarrassing and most of it I can’t fully remember.
I’ve been told of other embarrassing events I performed, which eventually resulted in my being placed in a room by myself and given sedatives to help me “relax.” I was given all sorts of medicines, went through a whole host of tests and discussions with specialists on how to treat and control this very rare disease, and no one knew the right answer. It was a case of controlling the disease from worsening and monitoring my condition very closely.
Eventually, I was transferred back to my local hospital and continued to have a wide range of tests, blood samples were taken every morning to be analyzed and, after three more weeks, I was released to go home with a cannular inserted into a vein in my wrist with 24 tablets to be taken during the morning and 12 at night. I also received IVIG treatment to boost my immune system every morning at the local hospital.
I am now awaiting a decision from my consultant regarding the next steps. He has to speak with specialists in London as he is also unsure about what to do. I’ve been signed off work until after Christmas, which I also find frustrating as I feel back to 100%, but deep down I know that is the right decision.
I hope this article gives other sufferers of this very rare disease assurance there are other people out there experiencing similar symptoms of this confusing and inexplicable disease for which hopefully leads to further research and ultimately a successful pathway to complete recovery.
May 2020
Since I wrote the above piece back in late December 2019, I’m feeling back to 100%. The doctors, specialists, occupational health therapists are all very surprised how quickly I seem to have fully recovered, and it’s all down to the support and treatment I’ve had.
It’s now early May, I’m still taking a large dose of meds including Lamotrigine, Levetiracetam, Prednisone, Adcal etc, which to be honest it’s now a case of a gulp of water and down the hatch. It’s now about 10 tablets in the morning and eight at night — massively down from 24 and 12.
I went back to work in early January on a carefully monitored and phased return, building back to full-time before the dreaded COVID-19 hit. I’m not going to lie, going back to work has been tough. The school I work at has moved on, which has is expected in the 12-18 months I’ve been in and out (mostly out). Different students. Different staff. Different expectations. It’s been hard for me, but harder and more frustrating for the brilliant people I’m lucky enough to work with.
When I got back into work I tried to pick up where I left off. It didn’t work, because my expectations of myself are so high. I wanted to know why, how, what had happened to this, that, and the other. I tried to rush back too quickly, and it didn’t work. I wasn’t listening or asking for help enough.
I thought I could pick up where I left off, but I couldn’t. My brain needed time to click back into action. Those billions of neurons needed time. Time, I thought I didn’t have. Fortunately, my employers have been incredibly understanding. They’ve supported me so much, something for which I am eternally grateful.
This is where I know I’m so lucky. I’ve read so many stories of people that are struck with different forms of encephalitis and other life-changing illnesses where they haven’t recovered enough to be able to return to work, or their employers haven’t been as understanding. At times, I feel guilty reading their stories.
As I write this I now only see my specialist twice a year and my meds are being reduced every 10 days. I’m back into full-time work in my original role and physically fit again, running at least three times a week, with lots of sport and the gym. I seem to have a “small” gap in my memory of about 12-18 months, but it could have been a lot worse.
So, it is very possible to make a completely successful and long-lasting recovery from AE and other forms of the disease. I read so many stories of people who have suffered from this terrible illness and are still suffering, so I wanted to write this to let people know there are success stories and you can — with the correct treatment and support network around you — return to full health and look forward to living the rest of your life.
Become an Advocate by sharing your story. It may result in someone receiving an accurate diagnosis who is suffering right now and is yet to be correctly identified. Submit your story with two photos to IAES@autoimmune-encephalitis.org
International Autoimmune Encephalitis Society (IAES), home of the AEWarrior®, is the only Family/Patient-centered organization that assists members from getting a diagnosis through to recovery and the many challenges experienced in their journey. Your donations are greatly appreciated and are the direct result of IAES’ ability to develop the first product in the world to address the needs of patients, Autoimmune Encephalitis Trivia Playing Cards. Every dollar raised allows us to raise awareness and personally help Patients, Families, and Caregivers through their Journey with AE to ensure that the best outcomes can be reached. Your contribution to our mission will help save lives and improve the quality of life for those impacted by AE.
Seizures can be scary events both for people who suffer from them and for their loved ones. Symptoms of a seizure typically include muscle spasms; loss of consciousness; sudden, rapid eye movements; or sudden mood changes; among other symptoms, and these can last from seconds to minutes1. These are the most severe seizures, but mild seizures, with more moderate physical and behavioral symptoms — such as stiffness of the muscles, feelings of déjà vu, anxiety, temporary confusion, or nausea — can also happen and may negatively affect health. During seizures, the body parallels what is happening in the brain: uncontrolled movements of the body can result from uncontrolled bursts of electrical activity in the brain.
Seizures are a response to hyperexcitability, meaning increased activity, of neurons in the brain, and hypersynchrony, meaning more neurons fire at the same time than normal. Seizures are very different across and within conditions. They can be generalized, affecting the entire brain from the beginning of the seizure, or focal, affecting one specific area although it may later spread. Frequent, unprovoked seizures called recurrent seizures may indicate that the person has a condition called epilepsy. Epilepsy is a chronic neurological disorder in which seizures can cause periods of unusual behavior, sensations, and negative effects on cognition such as a loss of awareness. However, because abnormal electrical activity can happen in response to other alterations in the brain such as brain injury and in response to medications, seizures can also be seen in other conditions.
One of these conditions is autoimmune encephalitis (AE). In AE, the body attacks the brain by creating antibodies against important neuronal proteins. Because these proteins help neurons communicate, the antibodies alter neuronal activity. Altering neuronal activation can lead to the changes that are seen in seizures (hyperexcitability and hypersynchrony). In fact, research shows that seizures in some patients can be a common symptom during the acute phase (early on in disease) of AE2. It is believed that antibodies against the neuronal proteins contribute directly to the disease processes and the development of seizures. It’s also possible that the process of neuroinflammation associated with AE, which increases the amount of toxic inflammatory molecules in the brain, can also contribute to the development of seizures2. Even once the inflammation has been resolved, the brain can still be predisposed to seizures or developing epilepsy, especially if the inflammation resulted in neuronal death3. However, whether epilepsy, a chronic disease, is developed in response to AE is not entirely clear. Some studies suggest that the risk of developing chronic epilepsy is low, from 10-15%4.
In different types of AE, seizures appear differently. Apart from the well-known tonic-clonic seizures (associated with jerking muscle movements), seizures in AE can also show up as faciobrachial dystonic seizures. These are characterized by abrupt involuntary movements, typically on one half of the face and arm of the same side. The frequency, response to therapies, and symptoms of the seizures themselves can all vary. However, the AE that most frequently manifest with seizures and chronic epilepsy are those mediated by antibodies against the LGI1, GABABR, and GABAAR; all-important proteins involved in neuronal communication5.
Are seizures associated with AE treated the same way as in epilepsy?
Antiepileptic drugs are the standard of care for people with epilepsy. Since seizures are a result of uncontrolled electrical activity and an imbalance of excitation and inhibition in the brain, antiepileptic drugs work by trying to restore that balance. For example, the drug clonazepam prevents seizures by increasing the effectiveness of a molecule in the brain called GABA, which helps the brain dampen the uncontrolled brain activity.
Now, although the normal path for people with epilepsy is treatment with antiepileptic drugs, it may not be particularly effective for people with seizures associated with AE. A study looking at a population of AE patients found that resolution of seizures happened even after discontinued antiepileptic drugs therapy6. In these young patients with AE who experienced unprovoked seizures at the onset of the disease there was a remission rate of 94%, meaning they stopped suffering from seizures, after they stopped taking antiepileptic drugs. Rather, immunotherapy seemed to be the important factor in controlling seizures. The researchers suggested that “long-term use of antiepileptic drugs appears not to be necessary to control seizures in AE”6.
Other studies support the idea that immunotherapy is more effective in attacking seizures in AE. One study looked at three different types of autoimmune encephalitis (anti-LGI1, anti-NMDAR, and anti-GABABR) and their response to immunotherapy and antiepileptic drugs7. They found that seizure freedom was achieved faster and more frequently after the use of immunotherapy than after the use of antiepileptic drugs. However, there may be a specific window in which immunotherapy is effective at controlling seizures.
Importantly, the researchers do mention that differences in seizures characteristics and therefore response to treatment may be due to the specific type of encephalitis. For example, patients with anti-GABABR encephalitis had an increased risk of developing seizures, meaning that the development of seizures may depend on the type of encephalitis7.
What do these findings mean for people with AE?
These differences in treatment response between AE and epilepsy point to an important trait that needs to be considered: the cause of seizures. In AE, antibodies generated against important neuronal proteins make the brain go awry. Therefore, one of the most effective ways to treat seizures may be attacking the root of the problem with immunotherapy. However, due to the variable nature of AE and the seizures associated with the condition, proper treatment with immunotherapy and/or antiepileptic medication will change from patient to patient.
What to do if someone is having a seizure?
During the most severe seizures, the person may not be able to control their body movements. For this reason, you may help them clear the area around them to prevent possible injury. If possible, place them on their side and provide cushioning for their head. There are additional indications suggested by the Center for Disease Control (become familiar with thesehere).
Rana, A., & Musto, A. E. (2018). The role of inflammation in the development of epilepsy. Journal of Neuroinflammation, 15(1). doi: 10.1186/s12974-018-1192-7
Vezzani, A., Fujinami, R. S., White, H. S., Preux, P.-M., Blümcke, I., Sander, J. W., & Löscher, W. (2015). Infections, inflammation and epilepsy. Acta Neuropathologica, 131(2), 211–234. doi: 10.1007/s00401-015-1481-5
Steriade, C., Moosa, A. N., Hantus, S., Prayson, R. A., Alexopoulos, A., & Rae-Grant, A. (2018). Electroclinical features of seizures associated with autoimmune encephalitis. Seizure, 60, 198–204. doi: 10.1016/j.seizure.2018.06.021
Spatola, M., & Dalmau, J. (2017). Seizures and risk of epilepsy in autoimmune and other inflammatory encephalitis. Current Opinion in Neurology, 30(3), 345–353. doi: 10.1097/wco.0000000000000449
Huang, Q., Ma, M., Wei, X., Liao, Y., Qi, H., Wu, Y., & Wu, Y. (2019). Characteristics of Seizure and Antiepileptic Drug Utilization in Outpatients with Autoimmune Encephalitis. Frontiers in Neurology, 9. doi: 10.3389/fneur.2018.01136
Bruijn, M. A. D., Sonderen, A. V., Coevorden-Hameete, M. H. V., Bastiaansen, A. E., Schreurs, M. W., Rouhl, R. P., … Titulaer, M. J. (2019). Evaluation of seizure treatment in anti-LGI1, anti-NMDAR, and anti-GABABR encephalitis. Neurology, 92(19). doi: 10.1212/wnl.0000000000007475
Lawyers have two great fears in life: 1) missing a deadline and 2) getting sick. Missing a deadline is scary and keeps us awake at night, but getting sick is about the worst. A simple cold or the stomach flu can require us to reschedule a deposition which could possibly change the course of the case and other deadlines, and it feels like all the dominos then start to fall. We’re humans, so we’re going to get sick, but we’re also lawyers, so we can plan for everything. Or wait, can we? I am a lawyer and I fell deathly ill while in private practice. It was unexpected, there was no accordingly tailored action plan, and it was worse than I ever could have imagined. In late May 2018, I was diagnosed with autoimmune encephalitis (AE) and it has forever altered the course of my life. My disease is a sneaky assailant. It took my body and it took my mind before I, or anyone around me, could get a serious hold on what was going on.
I suffered from insomnia for quite a while before I decided to take it seriously, but only because I was afraid it would start affecting my work. All signs pointed towards depression and anxiety. Lawyers become depressed from their workload and stress, that’s a fact. Who was I to believe I was any different, especially because of the hours I was working and the nature of the cases I was handling as a family law and criminal defense attorney. I didn’t want to admit to any mental health issues, but the slow and serious deterioration of my health finally made me admit and accept it. I was prescribed antidepressants to sleep and continued to plow through work. I told myself I’d take time off in the summer, I just had to make it through my busy spring. By the end of April, I was still an insomniac, my jaws were clenched, my hands were shaking, and my ears rang. In early May, I left work for a week’s break. Earlier that day, I had what I now know was a serious anxiety attack at my desk, and I knew I couldn’t stay at work any longer. I believed I needed time for my medication to kick in, which would hopefully allow me to sleep. On the surface, I told myself I would return to work very soon, but a deep down dark thought told me I’d never return to my office as I nearly collapsed out the door that day. Only six days after I left work, I checked myself into the psychiatric ward. My decline was obvious. I wasn’t very communicative, I stared a lot, I couldn’t sleep during the day or night, I no longer believed I was fit to drive with my children, and my body stopped working while I tried to swim or bike. I suffered from paranoia and confusion and hallucinated with prescribed sleeping medication. During my 48-hours in the ward, my mind started to slip and things, like knowing the date and reading a clock, became a challenge. I struggled to read and write. I cried and exhibited serious tremors. Something told me I didn’t belong in the ward, but I was desperate for help to sleep and to feel better.
From the time I left work until my time in the ward, my memory isn’t great. Once I left the ward, I nearly ceased to exist as a person and my memory is bare. My life during that time has been pieced together through records and my family’s recollections. For six days after I left the ward, my husband of 10 years took care of me like a child and wondered if I had dementia or was possessed, because of my cognitive impairment and strange behavior. At a follow-up behavioral appointment, my nurse practitioner immediately believed I had a neurological condition and expedited my referral to a local neurologist. Her astute thinking absolutely saved my life. However, the word “neurological” led my husband and family to think the worst. They believed I had a brain tumor. My neurologist’s diagnosis the next day was also life-saving for me. He believed I had AE but ordered more testing to rule out other conditions. Over the course of three days, I failed a neurological examination with flying colors, had an MRI image of my brain that was of poor quality because I shook so badly and could not lie still, and I underwent a spinal tap. I have only a few memories of the testing the first day and I don’t remember much after. My family cried for days and I was oblivious to everything. I repeatedly asked the same questions about what was going on but was fairly easily reassured and was compliant. My mother repeated over and over, “Thank God she doesn’t understand what’s going on.” Just 20 days prior, I had successfully defended an order to show cause hearing, but could not draw the face of a clock during my neurological exam. During the early morning hours, the day after the spinal tap, I had a grand mal seizure in bed that broke and dislocated my right shoulder. I was taken to CHI-St. Alexius Hospital in Bismarck, where I spent the next five days. My memories from the hospital are almost nonexistent and the ones I have are skewed. My health was incredibly fragile and there was serious discussion of having the Mayo Clinic’s airplane fly to Bismarck to retrieve me. While I was sick and rendered incompetent, my husband, family, and a few close lawyer friends took over my life and made all of the decisions for my cases, my role in my own law firm, my health care, and whether my husband had to sell our home and move us closer to our family. I had no idea any of this was going on. They all went into crisis mode to fight for my health and so that no one missed a step at the law firm. The thankfulness I have for my Superman husband, my beloved family, and my friends can never be fully explained. My health started to stabilize, so I stayed in the Bismarck hospital. Upon my release, I began a week of IV steroids to treat the AE. By the second day of treatment, my mind rallied, and my family saw the signs of me again. I underwent a CT scan that same week, which revealed blood clots in my right lung and leg, and three broken vertebrae in my back. It was also during that week that I was able to understand I was never mentally ill, but that all my health problems were the AE at work.
I went to the Mayo Clinic in June and my diagnosis and treatment were all verified, which was good news; it was the devil we were coming to understand. But the recovery process was slow from there. I struggled with people diverting my attention, noise, anxiety, fear, personal interactions, any public outings, could not drive, felt broken physically and mentally, was limited in movement, and was shaky and unsteady. I was mostly confined to my home for a year. I had to repair my mind, body, and spirit, and the Superwoman efforts required of me to survive and recover were overwhelming. With the love and support of my husband and family, and my determination to recover for the sake of my children, I rose to the challenge.
I never returned to my law firm after the onset of the AE, and I elected to retire from private practice based upon my health conditions. Starting in fifth grade, I only wanted to be a lawyer and have sacrificed more than I can explain to get to where I was in my career when the AE hit. Feeling like I lost the career I loved and the law firm I was so proud of, felt like the end of me and everything I knew. Although I have lost in unexplainable ways, I have gained an incredible new perspective on life. I have a lot of hope for the future. I also believe I can use the same drive and skills I honed to be a respected lawyer to accomplish the same goal I had as a lawyer: to help others. How I can best do that, only time will tell. I am currently working on a book to describe my experience with AE and I hope it is out for readers to enjoy in 2020.
As I’ve gone through this journey, I believe I’ve learned a few things along the way and hope to offer a little advice. 1) Take your work-life balance seriously. Upon deep soul searching, I know I was working too hard and not enjoying enough around me. I will live with that guilt and lots of “what-ifs” for life. 2) Make sure you surround yourself with colleagues and friends you admire and trust because your professional life requires it if you are ever unexpectedly debilitated. 3) Purchase long-term disability insurance. It is a great investment and was a life-saver for me. But most importantly, understand and read your policy before disaster strikes.
Become an Advocate by sharing your story. It may result in someone receiving an accurate diagnosis who is suffering right now and is yet to be correctly identified. Submit your story with two photos to IAES@autoimmune-encephalitis.org
International Autoimmune Encephalitis Society (IAES), home of the AEWarrior®, is the only Family/Patient-centered organization that assists members from getting a diagnosis through to recovery and the many challenges experienced in their journey. Your donations are greatly appreciated and are the direct result of IAES’ ability to develop the first product in the world to address the needs of patients, Autoimmune Encephalitis Trivia Playing Cards. Every dollar raised allows us to raise awareness and personally help Patients, Families and Caregivers through their Journey with AE to ensure that best outcomes can be reached. Your contribution to our mission will help save lives and improve the quality of life for those impacted by AE.
Now that frantic February is finally over its time to look back and take stock of what we achieved. World Encephalitis Day (WED) was started by the Encephalitis Society in October of 2013 and has been held every February 22nd annually since then. The purpose is to raise awareness of encephalitis globally. The International Autoimmune Encephalitis Society (IAES) has participated in WED annually since its formation. This year IAES designated the month of February to be Autoimmune Encephalitis (AE) Awareness month and will continue to exhibit the face of AE every year.
So, what did we do to bring attention to AE in February 2020? IAES President, Tabitha Andrews Orth, put together our 4th annual AE awareness video. This wonderful video features members who were kind enough to send photos of themselves in treatment and before and after shots. The AE Warriors Stepping Forward video was a great success so thanks to all who participated.
Our annual Virtual Arts Show 2020 was a beauty to behold. Filled with talent. Drawings and paintings, poems and short stories. It was an outpouring of emotion from the hearts of AE Warriors from all over the world. If you ever want to know what it feels like to have AE look no further.
We rolled out a selection of AE awareness products that provide the support and encouragement of everyone in the AE community’s desires. AE Warrior Gifts, now available year-round, features the Royal Registry certificates for the AE warrior ™ and Caregiver. These certificates recognize the heroism in battling AE by the patient and caregiver for their heroism under fire. Survival Kits for AE patients, caregivers, doctors, RNs, Kids, and parents were created, and many members gave these out. Candy bar wrappers with fun encouraging statements were developed for fundraising efforts and are available for free as well as a unique AE Medical Identification card IAES developed.
With all these great things going on there was still a magnificent topper to the month. Tabitha and her team rolled out a first of their kind Autoimmune Encephalitis Trivia Playing Cards Deck. These remarkable cards were developed with assistance by Dr. Dalmau and have questions and answers about AE to use for quiz games with families, who want to know more about AE, doubles as a rehabilitation tool or can just be used as playing cards. The original art on the cards was done by a fellow AE warrior, Julia King. Complimentary decks are being sent out to AE doctors on our Doctor’s List. The excited responses IAES is receiving from doctors about AE Trivia playing cards are filled with praise and congratulations in developing the ideal tool for AE patients, families and therapists. AE Trivia playing cards are on sale to the public and all proceeds will go to support AE research. Well done team.
So outreach for the first annual Autoimmune Encephalitis Month was a big success and thanks to all the members, caregivers and volunteers who put in their time and hearts to make it happen.
Of course, the culmination of the month is February 22nd and World Encephalitis Day. Many members sent in updates around this date and pictures to show before and after views that we decided to share some of them in case you missed them the first time around. So here are some great pictures and a few quotes to go with them.
From Renee Sanchez, “Well today’s the day! Almost exactly 5 months from her first seizure, which would be the last day of work and the beginning of this nightmare for our daughter, she is going back to work!”
From Paula Lee Ramirez, “Happy world encephalitis day
From ICU September 2017 to now. Symptoms started in August 12, 2017. I wasn’t admitted and believed I was sick until September 17,2017. Diagnosed on October 3, 2017 with ANTI-NMDA Receptor encephalitis. I have yet to relapse! ❤️
Lucy May Dawson, “Today is World Encephalitis Day. I, like 78% of people, had no idea what Encephalitis was until the words fell out of my neurologist’s mouth after I was misdiagnosed as having had a mental breakdown and had spent 3 months in a psychiatric ward…….Regardless, I am one of the lucky ones, and I hope that by continuing to post about encephalitis, someone will one day remember one of my posts when their loved one begins to act strangely, and they will ask their doctor to test for it, and it may just save a life”.
Daisy Garuvadoo: World Encephalitis Day today, from being critically ill with Anti-NMDA Receptor Encephalitis in Nov 2017, 2 years ago, having to relearn to walk, speak, to brush her teeth. to get dressed, to read, to write, to learn basic maths, to tell time and to regaining her cognitive abilities to Medical School and thriving. Yesterday, my daughter was honored for her research project related to Intrathecal procedures at her Medical School. INTRATHECAL RITUXIMAB TREATMENT(though the spine) IS WHAT SAVED HER LIFE.
Kimberly Anne Thompson I beat this. I have no lasting side effects. But awareness is so important… Because Encephalitis often presents with psychiatric symptoms it is often misdiagnosed… I spent six weeks in a Psychiatric Hospital originally diagnosed with having a Nervous Breakdown. I was given meds that only made My condition worse. It wasn’t until I started having Seizures and the Encephalitis began affecting My Heart that I was transferred to ICU and had a Lumbar Puncture which showed I had Anti-NMDA Encephalitis…. It is this delay that kills. I urge all Medical Professionals to consider Encephalitis in Patients that present with Hallucinations for the first time… You could save a life.”
Grace Harimate, It is world Encephalitis Awareness day today yesterday in NZ time…. as I contemplated sharing these images and my story, my heart was pounding … I wanted to forget but this ordeal you’ll never forget…I was misdiagnosed and mistreated with bipolar taking the wrong medications and wrong treatment for 6 years from 13y to 18y. Spending most of my teenage years in the mental health ward. But so glad I met the most amazing people in those years…..The hard part was to come when I woke up from a two-year coma… I was fully blind for one-year memory loss still tube fed etc. I was determined to walk … determined to get my eyesight back determined to get back on that horse determined to get a job … I walked into my 21st blind.
These awesome warriors and their brave care givers look at World Encephalitis Day and the new Autoimmune Encephalitis Month as a milestone. Where was I last year and where am I now? Some who have been floundering in a wilderness of lost memories have found their way or at least see a light at the end of their tunnel. Some are still, though making progress, struggling with issues others cannot even begin to imagine. Not only one year at a time but moment to moment. Some have been in comas only to wake up to a new truth, new situation, others are missing months or years of their lives. People they will never see again and new members of family and friends they are only meeting now. Such is the nature of Autoimmune Encephalitis. Your own body turning on you and messing up your brain. Sometimes making you hear, see, taste or smell things that are not there. Trying to make the family and friends in their lives understand the impossible.
March on brave warriors, continue to fight and savor your special month and the day set aside for you every year. May your lives look better next February.
Your generous Donationsallow IAES to continue our important work and save lives! Due to the coronavirus pandemic, the need for our services has surged exponentially. Some cases of COVID-19 have affected the central nervous system and medical researchers are suspecting the infection could cause ADEM, type of Autoimmune Encephalitis. Donations of any size are vitally important to meet the increased need in our community. If you have the ability to set up a reoccurring monthly donation, it will be greatly appreciated and will immediately begin to help patients and families during this historic time.
Become an Advocate by sharing your story. It may result in accurate diagnosis for someone suffering right now who is yet to be correctly identified. Submit your story with two photos to IAES@autoimmune-encephalitis.org
Autoimmune encephalitis (AE) can be hard to diagnose because its symptoms can vary widely and may be similar to symptoms of other illnesses or disorders. When a patient is in the hospital with symptoms that may point to AE, they typically undergo a series of tests and evaluations to determine if a diagnosis of AE is likely. These test results help doctors decide whether or not to begin immunotherapy treatment, the normal standard of care for AE. Eventually, patients get antibody testing to more precisely diagnose specific types of AE and refine treatment.
Typically, an MRI scan is included in the standard battery of tests when a patient with potential AE arrives at the hospital. MRI, magnetic resonance imaging, is a technique that uses a strong magnet to identify areas of the brain that may be overly active. Particular patterns of activity that can be seen with MRI, such as increased activity in brain regions including the hippocampus, are often associated with AE1. However, many patients with AE have normal-looking MRIs, so MRI is not a perfectly accurate tool for diagnosis. A different type of diagnostic imaging called 18F-FDG PET might be able to detect certain types of encephalitis that would be missed with MRI1.
What is 18F-FDG PET?
18F-FDG PET imaging, which stands for [18F]fluorodeoxyglucose positron emission tomography, uses a radioactively labeled glucose molecule to identify parts of the body or brain that have unusual amounts of activity. Glucose is the body’s main source of energy, so PET scans allow doctors to visualize areas that have high energy metabolism, or hypermetabolism. An area that is more active uses more glucose and shows up more strongly on a PET image. FDG PET is often used in cancer diagnosis because it can be used to locate parts of the body where cancer cells are growing and using a lot of extra energy2,3.
FDG PET imaging is also useful for identifying patterns of activity in the brain that are often associated with AE1,4. Many patients with a specific type of AE called limbic encephalitis who receive an FDG PET scan have hypermetabolism in a part of the brain called the medial temporal lobe5,6. This part of the brain is involved with emotion and memory, which are often related to symptoms of AE. However, there is no one signature activation pattern that is consistently associated with limbic encephalitis, and other patients have shown patterns of unusually low metabolism (hypometabolism) in the medial temporal lobe or hypermetabolism in different brain regions, such as parietal and occipital lobes1,9.
Another subtype of AE called anti-NMDA receptor encephalitis may also be easier to diagnose with FDG PET than with MRI7. This type of encephalitis that affects NMDA glutamate receptors in the brain is often associated with hypermetabolism of glucose in the frontal and temporal lobes and hypometabolism in the occipital lobe7. A study at Johns Hopkins looked at PET and MRI scans of 5 patients with anti-NMDA receptor encephalitis and found that all 5 had abnormal FDG PET scans but no abnormalities detected with MRI scans1.
Doctors have been able to diagnose these types of AE based on FDG PET results, even when that patient’s MRI scans appear normal4. One study of AE patients found that 85% had abnormal FDG PET scans, a greater percentage than for either MRI or EEG, suggesting that FDG PET may be a more sensitive measure8. For these reasons, researchers believe FDG PET may be an important tool for getting specific and precise diagnoses of AE6.
PET vs MRI
One drawback of using PET scans for early diagnosis is that they are typically not as quick and easy to obtain as an MRI. Many hospitals require time to schedule PET imaging so it cannot be completed when a patient is in the hospital with possible AE symptoms that need to be evaluated. MRI, on the other hand, can usually be performed on an emergency basis, so these results can be obtained more quickly and guide early treatment decisions10,11.
Another argument against implementing PET imaging as part of an initial battery of tests to diagnose AE is that a small amount of radiation is injected into the body in the form of the radioactive glucose tracer. However, many patients with AE symptoms already get PET scans of the body to check for tumors, so performing a PET scan of the brain at the same time would not require any extra radiation and could help doctors to get more information on what is going on in the brain6.
More research will be needed to determine exactly how accurate FDG PET can be at diagnosing different subtypes of AE, but since PET scans offer more precise diagnostic powers than MRIs, FDG PET shows promise as another tool to help with the diagnosis of AE.
Your generous Donationsallow IAES to continue our important work and save lives!
Become an Advocate by sharing your story. It may result in an accurate diagnosis for someone suffering right now who is yet to be correctly identified. Submit your story with two photos to IAES@autoimmune-encephalitis.org
References:
Solnes, L. B., Jones, K. M., Rowe, S. P., Pattanayak, P., Nalluri, A., Venkatesan, A., … Javadi, M. S. (2017). Diagnostic Value of 18 F-FDG PET/CT Versus MRI in the Setting of Antibody-Specific Autoimmune Encephalitis. J Nucl Med, 58, 1307–1313.
Gallamini, A., Zwarthoed, C., & Borra, A. (2014). Positron Emission Tomography (PET) in Oncology. Cancers, 6(4), 1821–1889.
Shukla, A. K., & Kumar, U. (2006). Positron emission tomography: An overview. Journal of Medical Physics, 31(1)
Deuschl, C., Rüber, T., Ernst, L., Fendler, W. P., Kirchner, J., Mönninghoff, C., … Umutlu, L. (2020). 18F-FDG-PET/MRI in the diagnostic work-up of limbic encephalitis. PloS One, 15(1).
Baumgartner, A., Rauer, S., Mader, I., & Meyer, P. T. (2013). Cerebral FDG-PET and MRI findings in autoimmune limbic encephalitis: correlation with autoantibody types. Journal of Neurology, 260(11), 2744–2753.
Morbelli, S., Djekidel, M., Hesse, S., Pagani, M., Barthel, H., Committee of the European Association of Nuclear Medicine, N., … Imaging, M. (2016). Role of 18F-FDG-PET imaging in the diagnosis of autoimmune encephalitis.
Leypoldt, F., Buchert, R., Kleiter, I., Marienhagen, J., Gelderblom, M., Magnus, T., … Lewerenz, J. (2012). Fluorodeoxyglucose positron emission tomography in anti-N-methyl-D-aspartate receptor encephalitis: distinct pattern of disease. Journal of Neurology, Neurosurgery, and Psychiatry, 83(7), 681–686.
Probasco, J. C., Solnes, L., Nalluri, A., Jesse Cohen, B., Krystyna Jones, B. M., Zan, E., … Venkatesan, A. (2017). Abnormal brain metabolism on FDG-PET/CT is a common early finding in autoimmune encephalitis. Neurol Neuroimmunol Neuroinflamm, 4, 352.
Lee, S. K., & Lee, S.-T. (2016). The Laboratory Diagnosis of Autoimmune Encephalitis. Journal of Epilepsy Research, 6(2), 45–50.
Graus, F., Titulaer, M. J., Balu, R., Benseler, S., Bien, C. G., Cellucci, T., … Dalmau, J. (2016). A clinical approach to diagnosis of autoimmune encephalitis. The Lancet.Neurology, 15(4), 391–404.
Graus, F., & Dalmau, J. (2016). Role of 18F-FDG-PET imaging in the diagnosis of autoimmune encephalitis – Authors’ reply. The Lancet Neurology, 15(10), 1010.
IAES takes pride in keeping our community up-to-date with the latest news in the field of autoimmune neurology and topics that directly impact our lives. Our motto, “Education is Power” continues to ring true as education does help to steer the best outcomes. Our motto is particularly appropriate in regard to the COVID-19 Virus.
Information about the COVID-19 continues to dominate world news and likely will for some time to come. We have prepared a flyer of the preventive measures you can take as recommended by the guidance from the Centers for Disease Control and Prevention (CDC). You can print out and post this flyer at home, school, doctor’s offices, work, place of worship, or anywhere in your community. In addition, we have created an ‘info meme’ that can be easily and widely shared on social media platforms. International Autoimmune Encephalitis Society continues to monitor the situation with the AE community in mind.
The severity of illness or how many people will fall ill from COVID-19 is unknown. However, you are at higher risk if you are immunocompromised due to the immune suppressant medications used in the treatment of autoimmune encephalitis. IAES encourages you to stay informed by following updates from the CDC and/or your local health department. The likelihood of getting COVID-19 depends on where you live in the world and may change quickly.
COVID-19 is a novel virus, and there is still much we have yet to learn. One fact we do know is that an infected person can be a carrier, capable of spreading the virus to others for several days before they begin to show symptoms or know they are sick. Each infected person has the ability to pass the virus on to 2 or 3 people. Implement these hygiene practices now to avoid getting sick. Because there is no way of knowing who a carrier might be, assume you may come in contact with someone who is and institute these preventive hygiene practices and pro-active planning steps right now.
In addition to your advocacy of spreading COVID-19 preventative awareness and implementing the recommended hygiene habits the CDC recommends, plan and prepare ahead should you need to self-quarantine. If a member of your household becomes sick, all family members will have to self-quarantine for 14 days. Because the AE patient’s immune system is compromised, this also means that it takes AE patients longer to fight off a virus and the self-quarantine length may extend beyond the mentioned 14 days. Make sure you have enough food, water, other basic supplies on hand should you need to remain at home for 14 days. Find out if your pharmacy delivers and make sure you will have enough of your medications on hand. Contact your doctor should you have a fever, cough or shortness of breath.
CREATE A NEIGHBORHOOD SUPPORT CIRCLE
I live in the state of Oregon in the U.S.A. The first two cases of COVID-19 were announced last weekend and are located 15 minutes from my home. The Nursing facility in Washington State that was so badly impacted that is being reported daily on national news is a few hours away. While I was stocking up at the supermarket for supplies the other day, seeing the bare shelves, I felt an eerie feeling of being involved in the beginning of an impending community health crisis.
The woman who helped me at the Deli Counter shared a story of how her friend, who was a second-tier transportation bus driver for the Nursing Home that had been so hard hit had been instructed to self-quarantine and it was not being reported on the news. I realized that there was a true possibility that my husband, son and I may have to self-quarantine at some point during this virus outbreak and we do not have any family support.
As I drove home with my car laden with groceries, I started thinking about staying home for two weeks without back up support. We have lived in the same house for 30 years, and this past year our next-door neighbor, who we loved dearly, moved away and our neighbors directly across the street sold their house. Both neighbors had been a wonderful support to us and us to them over the years and I mourned the loss.
However, we had started to get to know the young couple across the street and we were already lending each other a helping hand. She has a home business as a massage therapist and a 14-month-old daughter. They were at high risk, I realized. There is a couple in their 80’s two doors up from us and they have no family. They are at high risk. Our new neighbor next door, a bachelor and Uber driver is high risk. Another neighbor of ours is a mailman and his wife works at the local elementary school. They are at high risk. The couple next door on our other side are in their late sixties and he has health concerns. They are at high risk. Next to them is a couple whose sons are grown, married and parents now, empty nesters who are not high risk. I realized that the first 8 houses on our block have 6 high-risk households. If I have concerns, they must too. I thought we need to create a neighborhood support network. We will be the best possible back up system for each other and everyone’s concerns can vanish. That’s exactly what I did.
One by one I contacted my neighbors and explained my idea. If one of us became ill, we would have to self-quarantine. Other neighbors in the support network could drop off supplies and meals and pick up prescriptions or whatever was needed for that household. We could all chip in and help where and when we could. We would become our own best built-in back-up system.
The smiles, relief, and enthusiasm everyone greeted the idea with did not surprise me. We needed each other, and it would be a great way to get to know our new neighbors. I opened a text message group with everyone included and typed up a telephone directory. Using a plastic protective sleeve, I included the IAES preventative health measures COVID-19 flyer back to back with the directory. I texted the ‘Neighborhood Support Network’ group to let my neighbors know I would leave their telephone list by their front door. My phone started pinging away as my message was read and I got the chance to visit with all of my neighbors as they greeted me upon my arrival. We laughed and joked and shared stories with each other. Everyone was so excited about the idea and grateful to live among such supportive neighbors.
I feel safer tonight. I know that if one of my neighbors gets sick or just needs a helping hand, they will text or call. Everyone was ‘all in’ and ready to do their part to support the whole. We are going to be just fine on SW Parkview Loop in Beaverton, Oregon. We plan on keeping our network as a permanent network solution too. There is a silver lining in everything I thought. My life just became richer. I hope you do the same in your neighborhood. We are #StrongerTogether.
Little things, just little things were first noticed by our immediate family. The need to recite over and over the details of how a decision was made, excessive talkativeness, repetitive conversations. Outbursts of anger over inconsequential events, vocalizations of “yep, yep, yep” and a stutter-step when that happened. Something was not right. Periodic feelings of having a “brain spasm” were added to the mix.
Visits to our personal care physician, referral to a neurologist, MRIs and EEGs all resulted in a conclusion that Jeri was just stressed out. After our son’s wedding, everything would be alright. It wasn’t. The wedding was a big success but for Jeri, concentrating on the many details was difficult, to say the least. Our college friends noticed immediately that something was not right. “She seems to not be herself, she gets angry easily, what’s up?”
Could it be a recurrence of the chronic Lyme disease from 8 years ago? Off to the holistic physician that successfully treated Lyme disease. The approach there was to test for exposure to environmental toxins and Lyme. Blood was drawn and then we left for a couple of weeks to go to our cottage in Canada. In those two weeks, our Canadian friends also came to us and asked if something was going on. The repetitive conversations continued along with withdrawal from group conversation. A couple of times Jeri blanked out for a few seconds and became worried-looking, really concerning our friends.
Back from the cottage the follow up with the Lyme doctor revealed that she was slightly positive on the Lyme test. (Lyme diagnostics is difficult and subjective – a discussion for another time.)That is probably what was going on. Back on antibiotics and several nutritional supplements – for 24 hours. Then our journey really began.
“Mom’s had a seizure, I’m following the ambulance to the hospital.” Our two adult sons living at home had found Jeri having a seizure shortly after going to bed. Another seizure while in the ER. The workup revealed that her sodium levels were dangerously low. Correction of the hyponatremia began along with MRIs and other scans. Five days as an inpatient to correct the sodium levels and all tests came back negative. No infectious causes, no tumors, must just be a case of spontaneous SAIDH (Syndrome of Inappropriate Antidiuretic Hormone Secretion). It happens, that can be corrected with diuretics and salt pills. Take anti-seizure medicine and follow up with a neurologist.
At this point, the reader needs to know a little about our family. For years Jeri was a researcher in a biochemistry lab and up to a couple of years ago, a practice manager for a busy physician’s office. I’m a Ph.D. biochemist and molecular biologist. One son is a newly trained nurse and one daughter-in-law is a very experienced pediatric intensive care nurse. Jeri’s brother-in-law is an attorney with over 20 years’ experience in large pharma oncology and has a Masters in chemistry. To say that there were many opinions on what was going on is the understatement of the year. A lot of family knowledge and experience were being tapped, all out of concern, love, and with the best of intentions. Conversations with physician friends and nurses suggested a myriad of causes. None of us got even close to the cause.
The ‘spells’, absent episodes, memory issues, and cognitive decline all continue and increase in frequency. We were home for a week and then another big seizure puts her back in the ER and again admitted to the hospital. Again, all scans and EEG are normal. The doctors in the regional hospital are again scratching their heads. Despite repeated requests, the hospital physicians and our personal neurologist resisted performing a lumbar puncture. Why? We were told there was simply no indication that would justify such a high-risk procedure. Must be the SIADH. Go back to your local neurologist and nephrologist.
A 72 hour EEG was ordered. This was stopped after 24 hours since we noted so many (~30) ‘spells’ and no further recording was needed. Like two spot EEGs before, nothing showed up. The local neurologist was stumped, calling it a real mystery. We again ask for an LP and testing but were refused on the basis that he didn’t know what to test for. As a shot in the dark, testing was ordered for serum anti-NMDA receptor. Negative results. Sodium levels stay a bit low, but near normal. Frustration all around.
Escalating the case was now a family priority but we were stymied by the long wait (2 months!) to get into the UPenn neurology group. A week after the last neurology visit another seizure. A couple of days later we hear a crash and see Jeri at the bottom of the stairs having a seizure, this time with a gash to the head. Back to the ER after a very irrational and angry outburst. Another seizure in the ER and another admittance to the local hospital. The next morning during rounds the floor neurologist is in the room and the hospitalist (physician in charge of cases on that floor) pops in to see how things are going. She asks the neurologist if she is going to order an LP and the neurologist says no, there is no need. The matter is dropped. No words can describe our frustration and helplessness at this point. My son and I discussed the situation and decided to go to the hospitalist and ask for her intervention in getting the case moved to UPenn. She agreed but was doubtful that she could get her transferred. To her and our surprise, UPenn neurology agreed right away!
We were just so lucky to have the case taken over by UPenn and a group of physicians that have been integral to the discovery and treatment of autoimmune encephalopathies. Within a week we had a diagnosis of anti-LGI-1 autoimmune disease and a week after that we began immunosuppression therapy via a five-day course of steroid infusions and an infusion of Rituximab.
We’ve been home a week, continuing anti-seizure medicine, oral steroids, salt supplementation, and diuretics. No seizures so far! We are seeing small improvements in cognitive ability and memory. We have a long way to go but are hopeful. The second infusion of Rituximab will happen in about a week.
Lessons learned:
Unfortunately, I think we can consider that knowledge of auto-immune encephalopathies is pretty much non-existent to the average physician and even most neurologists. The resistance to exploit all avenues of testing after repeated presentations to the ER and negative results of conventional diagnostics needs to change. That change will only come with physician education. Also, symptoms can be very, very subtle at first and not consistent from person to person. Like a lot of other neurological conditions, the symptoms are common to many different causes.
Now that the mystery is solved the recovery can begin. Another Zebra identified.
Become an Advocate by sharing your story. It may result in an accurate diagnosis for someone suffering right now who is yet to be correctly identified. Submit your story with two photos to IAES@autoimmune-encephalitis.org
February-12-2020| by: Kerry Jones I am one of the lucky ones. But, in a way, I think I inadvertently helped make my own luck by contacting the Mayo Clinic when I did. A little over two and a half years ago, my wife and I flew from our home outside of Kansas City, MO to the San Francisco Bay Area to visit family. When we returned and got off the plane in late May, my memory was almost completely gone except for a few instances from my childhood which, since I was 68 at the time, was a long, long time ago.
I started having seizures. At first, just a couple of times a day, gradually increasing to 20 or more a day. I had frequent feelings of nausea and incredible weakness (I couldn’t walk even an 8th of a block without being completely exhausted.) I contacted my physician and he tried to schedule me with the neurology department. They subsequently referred me to another neurological testing group, but scheduling with them was delayed while they were awaiting insurance approval. In retrospect, this may have been another stroke of luck, because, with my symptoms getting worse, I finally contacted the Mayo Clinic in Rochester on a Thursday or Friday in July. Apparently I used the right buzz words because they responded right away and said, “Can you come in on Monday?” Even though they were an out of network provider on my insurance plan, my wife and I jumped in the car and drove up there.
After being run through a battery of tests and being seen by several doctors, I was diagnosed with LGI1 Autoimmune Encephalitis, and placed under the care of Dr. Eoan Flanagan who began treating me with high dosage prednisone – this was about the first of August. I had my last known seizure in late October, though most of the other symptoms have persisted. At this point, I’m certainly not cured, but am adjusting to a new reality.
My memory is still very spotty. For example, as I am writing this, we are once again in California visiting family. While talking to my daughter, who just recently moved back here from Kansas City, I mentioned that I hadn’t been back to California since this had happened and that I was leery about flying even though I knew intellectually that flying had nothing to do with causing the disease. My wife gently reminded me that yes, we had flown out here just last year. I have no memory of that. I lived in this area a large portion of my life, but as we drive around, it’s like I’m in a foreign country. I don’t recognize much of anything I see. The funny thing about my memory loss, though, is that I remember people, just not places or events. I’m currently in the process of being weaned off the prednisone and replacing it with Rituxan (I had my first Rituxan treatment last August.)
I have no idea what the future will hold, whether I’ll get my memory back or not. But I’ve determined to not let that impede my enjoyment of life while it happens. It’s hard sometimes when I’m with friends or family when the conversation turns to reminiscing about a past which I can’t remember, but I know there’s nothing I can do about that. My new motto is “Live in the Moment.”
Become an Advocate by sharing your story. It may result in accurate diagnosis for someone suffering right now who is yet to be correctly identified. Submit your story with two photos toIAES@autoimmune-encephalitis.org
International Autoimmune Encephalitis Society founded AE Awareness Month in 2020 to shine a light on Autoimmune Encephalitis. AE Awareness Month is the biggest month of the year for the AE community. It is a time when the entire community comes together to raise awareness of this treatable group of diseases.
Our main goal is to raise awareness among the public and medical community, especially first responders such as Psychiatrists and Emergency Room Clinicians, about AE and its impact on patient’s lives and the lives of the family members, loved ones and caregivers who support them.
Anyone can get involved in this International effort. Get involved today to shine a light of autoimmune encephalitis.
1.
Autoimmune Encephalitis Trivia Playing Cards
AE Trivia Playing Cards
IAES in collaboration with Dr. Josep Dalmau has created the first product in the world specifically addressing the needs of the AE Warrior™ and those impacted by AE. ALL proceeds will support Dr. Dalmau’s research group. Stay tuned for the announcement of this exciting educational and rehabilitation tool. It is destined to become the most vital product anyone touched by autoimmune encephalitis should purchase. A true game changer in helping you to become a strong advocate, receive an outstanding educational foundation about AE doubles as a rehabilitation tool!
Become an IAES Angel and receive a facebook picture frame announcing that you have
The IAES Angel has lifted IAES upward by ensuring that comfort, guidance and improved health is brought into an AE patient’s life. IAES Angels are motivated by their Spirit of giving. They are Champions in raising AE awareness.
When you become an #IAESANGEL,International Autoimmune Encephalitis Society will send you this badge and profile frame to place on your Facebook page or Website. As badges ‘take flight’ heralding IAES has been ‘touched by an angel’, others will take notice and they too may find their wings. Together, we will create a future where AE is eradicated from this world and only referenced in medical history books.
3.
AE Warrior and AE Caregiver Royal Registry Certificates
The Royal IAES Registry designates The AE Warrior™ and AE Sentinel with Royal Title. In recognition of their heroism under fire. The Royal IAES Registry is the highest honor to be bestowed upon those engaged in the mighty autoimmune encephalitis battle. Without warning and within an instant, these unprepared citizens were thrust unto a perilous fire raging battlefield. To fight demanded that they dig deep into the depths of their soul for the inner-strength they had to summon to save their life or the life of the one they loved. This act is so rare IAES sanctifies and affirms by sealed decry the bestowing of Royal Title into the IAES Registry.
4.
Watch and Share our Awareness video AE Warriors Stepping Forward
AE Warriors Stepping Forward
This inspiring video shows the wide age range and diversity of AE patients, it explains what AE is in simple terms and provides key RED FLAG warnings to any medical professional who views it. This is IAES’ 4th annual awareness video. Proceeding videos have had a powerful impact on raising AE awareness and has lead to many patients receiving an accurate diagnosis.
5.
Get your Story in your Local Newspaper or Television Station
Breaking News!
IAES has done the work for you. Download our press release and directions. Reports will use quotes from experts cited in the press release as well as contacting the doctor who diagnosed you. This raises awareness on a much larger scale and only involves a few simple steps.
6.
Hold a FUNdraiser or Awareness Event at Work, School or Your Home
By going to our FUNdraiser Page, you will see several ideas for all ages that allows you to have FUN and raise awareness for AE at the same time.
7.
Assemble AE Survival Kits
Share your love and encouragement by purchasing a survival kit, (Goodies not included). IAES has created 11 different variations of these kits that are bound to bring smiles of pleasure to those who receive them. Create a kit for your AEWarrior™, AE Mom, Doctor, Psychiatrist, Nurse, Infusion day, Child or Caregiver. These kits are available year-round.
8.
Raise Awareness with IAES Candy Bar Wrappers
IAES has created 14 unique candy bar wrappers you can raise some sweet awareness. These free wrappers include sentiments for people in the AE community and public. These wrappers can be given as your simple act of kindness or used as a fundraising vehicle. They are a wonderful way for children and siblings to get involved in fundraising and raising awareness as well. Candy wrappers will be available throughout the year.
9.
Print and share this AE Infographic
Post this Infographicthroughout the month on your social media platforms and also download it onto card stock paper and give it out at school, work, gym or your place of worship.
Tour the IAES Virtual Art Show and share the link on your social media platforms. Showcased is art in a variety of forms done by patients, siblings and caregivers of all ages. Experience a special insight into AE through their eyes and experiences.
It is important that we all stay well informed. When a person receives a diagnosis of autoimmune encephalitis, they want to do whatever they can to improve their health. Some will reach for what appears to them to be a positive action and decide to change their diet. This can have very negative unintended consequences. To ensure your safety, and in IAES’ commitment to providing accurate information to assist you in being well informed on your road to recovery, today I’m going to give you a simple explanation about the Keto Diet.
What is it?
KETO is a diet that excludes carbohydrates completely. Basically, you eat just proteins and fats. Carbohydrates are the main fuel generator for the body (and especially the brain). They transform into glucose (the fuel). By switching to the KETO diet, one leaves the body without the fuel source. So, the body learns to turn other stuff into fuel. In this case, mainly fat. But also, the muscles. That’s what we call “putting the body into a state ok Ketosis). Is this good? Is it bad? For some people it is good. For some it is bad. For some it is an unnecessary risk, meaning there is no proof whatsoever that it helps, but there is proof that it can do some damage.
Who is a candidate for the Keto Diet?
Keto diet is recommended in a small number of diseases:
– severe Epilepsy, irresponsive to golden standard medication (being more efficient in children);
– Glucose Transporter Type 1 Deficiency Syndrome (a genetical disease that does not allow the body to produce GluT1 , so the brain does not get glucose- fuel. The ONLY treatment in this situation is keto diet!);
– it is also used by some nutritionists with patients that need to lose weight.
!!!! It needs to be assessed, recommended and monitored by a doctor!!!
There is no proof that the KETO Diet works in Autoimmune Encephalitis. (It can be recommended in severe Epilepsy post-Acquired Brain Injury in AE, but it does not treat AE, it treats the Epilepsy resulted from a brain injury from AE. As you know by now, Epilepsy and Seizures are not the same things. In AE we may have seizures, due to brain swelling and antibodies attacking our healthy brain cell. This is why we need immunosuppressant/ immunomodulatory treatment to control the disease.
Epilepsy is a disease resulted from the brain being injured and scarred.
Epilepsy can happen in AE but having seizures does not mean you have Epilepsy! Your doctor needs to asses that and tell you that you acquired Epilepsy!
Why? And why not the KETO Diet?
Now that you understand who an appropriate candidate for the Keto Diet would be, let’s discuss what can happen if you try the diet on your own without discussing it with your doctor.
Why does the Keto Diet need to be recommended by your doctor and monitored all the time?
Because it can be dangerous! Yes, it can be.
For diabetics. Also, people with kidney disease or who take medication that increases the risk of Kidney disease. For example, It can lead to major weight loss, below the normal BMI, that can endanger hormonal balance. It can increase pressure on the liver and kidney and eventually eats up your muscles too. The body can enter into ketosis (dangerous for some people).
KETO Diet is not easy, not harmless, not for anybody and not proven effective in AE.
Your doctor needs to assess and recommend that for you or for your child because it can be dangerous and can cause harm. If you have the conditions stated at point 2, then you might benefit from a very well supervised KETO Diet. Always ask your doctor! And please, don’t recommend it to other people, because it can harm them! Our concern is your safety and sharing accurate information for your best overall health.
Your generous Donationsallow IAES to continue our important work and save lives!
Become an Advocate by sharing your story. It may result in accurate diagnosis for someone suffering right now who is yet to be correctly identified. Submit your story with two photos to IAES@autoimmune-encephalitis.org
Imagine you’re a bright twenty-something with a new job and a new relationship. Everything seems to be going your way until you start becoming paranoid and acting erratically. Then come the hallucinations and seizures. You’re admitted to a hospital where you’re (incorrectly) diagnosed with a psychiatric disorder. You swing from violence into a state of immobility and stupor. And perhaps even scarier? You don’t remember any of it. Sound like a nightmare? Well, it actually happened to Susannah Calahan, who details her terrifying story first-hand in her 2012 book Brain on Fire: My Month of Madness.
What caused these frightening symptoms? The answer was a disease that had only been discovered a few years earlier (right here at Penn!): NMDAR encephalitis. There are four main phases of the disorder. In the prodromal phase, many but not all patients experience a flu-like illness for up to 3 weeks. The psychotic phase is accompanied by delusions, auditory and visual hallucinations, depression, paranoia, agitation, and insomnia. At this stage, most patients are taken to the hospital, where around 40% are misdiagnosed as having a psychiatric disorder like schizophrenia. As this phase progresses, seizures are very common (although they can occur at any time throughout the illness), as well as involuntary muscle movements like lip-smacking or grimacing, catatonia (muscular rigidity and mental stupor), impaired attention, and memory loss. The next phase is unresponsiveness, which includes symptoms like the inability to speak, loss of voluntary movement, and sometimes abnormal muscle contractions that cause involuntary writhing movements. The last phase is the hyperkinetic phase and is characterized by instability of involuntary bodily functions such as breathing, blood pressure, heartbeat, and temperature. Many patients who breathe too slowly often need to be placed on a ventilator at this stage. The decline to ventilator support can progress very rapidly after several weeks in the psychotic stage, and ultimately patients can be hospitalized for several months with the disease1–3.
What does NMDAR encephalitis actually mean? This disease is an autoimmune disorder, meaning the body’s immune system mistakenly attacks its own healthy cells. Normally the body identifies foreign substances by making something called an antibody that recognizes a unique part of the invader, thus targeting it for attack and destruction. In NMDA encephalitis though, the immune system attacks the brain (that’s where to term encephalitis comes from), specifically a type of neurotransmitter receptor called an NMDA receptor (NMDAR). These receptors bind the neurotransmitter glutamate, and play an important role in learning, memory, cognition, and behavior. In fact, the symptoms of NMDAR encephalitis resemble those caused by drugs such as ketamine or PCP that prevent the activation of NMDARs. For instance, at low doses ketamine and PCP cause paranoia, false perceptions, and impaired attention (like the early stages of NMDAR encephalitis), and at higher doses these drugs cause psychosis, agitation, memory and motor disturbances, and eventually unresponsiveness, catatonia, and coma2. Several mechanisms have been proposed to explain the symptoms caused by antibodies targeting the NMDAR, but most of the evidence seems to support the idea that the receptors get removed from the cell surface and internalized. For instance, experiments in the laboratory demonstrate that when animal neurons grown in a dish are exposed to patients’ anti-NMDAR antibodies, the number of NMDARs on the cell surface decreases as the amount of antibodies increase. When the antibodies are removed, the number of NMDAR receptors on the cell surface returns to baseline within 4 days1.
It’s easy to remove antibodies in a dish, but how do doctors get the body to stop producing antibodies against itself? Step one is identifying what triggers antibody production in the first case. Interestingly, NMDAR encephalitis predominantly affects women, and ovarian teratomas (a type of tumor made up of multiple types of tissues, which can include nervous system tissue) are responsible for 50% of cases in young women2. In patients who have some sort of tumor, removal improves symptoms in 75% of cases. Interestingly, herpes simplex virus can also cause encephalitis (inflammation of the brain), and about 20% of these patients also develop antibodies against NMDAR2. Treatment consists of immunotherapy: corticosteroids, IV infusion of immunoglobulins, and/or plasma exchange1, however patients with a viral trigger tend to be less responsive to treatment than those with a teratoma trigger or the 50% of patients with an unknown trigger2. Once treatments begin improvements in symptoms start within a few weeks, though return to baseline functioning can take up to three years. Rehabilitation is required for many patients after they leave the hospital. Deficits in attention, memory, and executive function may linger for years, but luckily over 75% of patients with the disease recover to at or near baseline neurological functioning1.
Doctors and scientists hope to develop new treatments involving immunotherapy combined with small molecules that are able to access the brain to directly combat the effects of anti-NMDAR antibodies, ideally leading to faster control of symptoms and shorter recovery time2. A brand new animal model of the disease was just described last week that will hopefully lead to more discoveries about how the disease is triggered and potential new therapies4. And with increased awareness of autoimmune disorders against the brain, doctors will be able to more quickly correctly diagnose patients with this illness and get them the treatment they need.
References:
Venkatesan, A. & Adatia, K. Anti-NMDA-Receptor Encephalitis: From Bench to Clinic. ACS Chem. Neurosci.8, 2586–2595 (2017).
Dalmau, J. NMDA receptor encephalitis and other antibody-mediated disorders of the synapse: The 2016 Cotzias Lecture. Neurology87, 2471–2482 (2016).
Dalmau, J. et al. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol.7, 1091–1098 (2008).
Jones, B. E. et al. Anti-NMDA receptor encephalitis in mice induced by active immunization with conformationally-stabilized holoreceptors. bioRxiv 467902 (2018). doi:10.1101/467902
Your generous Donationsallow IAES to continue our important work and save lives!
Become an Advocate by sharing your story. It may result in accurate diagnosis for someone suffering right now who is yet to be correctly identified. Submit your story with two photos toIAES@autoimmune-encephalitis.org
I have been a nurse since 1985. I was working as a nurse case manager when I was at work in December 2017. A co-worker, who I have worked with for years, noticed I was acting strange- laughing inappropriately, busy but not really doing work. We shared an office and she took my keys out of my purse because I had talked about going home and that idea scared her.
What neither of us knew at the time was that she saved my life. Because I couldn’t find my keys, I went back to the unit I worked on, shortly after that I had a seizure. I was hospitalized and after a few days of testing, I was diagnosed with anti-NMDAR encephalitis. Anti-NMDAR stands for anti-N- methyl-D- asparate receptor encephalitis. It is an autoimmune disease where the body creates antibodies against the NMDA receptors in the brain. The antibodies disrupt normal brain signaling and can cause seizures, memory problems, cognitive issues, speech disorders, neuropsychiatric symptoms as well as other symptoms.
I was treated with steroids, IVIG and plasmapheresis. I had inpatient and day therapy rehabilitation. I also did a computer cognitive therapy program. Recovery can be slow. Many patients with autoimmune encephalitis are left with memory problems, cognitive deficits and have problems in situations that are cognitively demanding. Memory continues to be an issue since my diagnosis with AE.
I have a calendar and use my phone to keep track of my schedule but what I have found is that people treat me as I was before, that would be great if I had my normal memory, but I don’t. That is part of the problem with having an invisible disability. If you didn’t know what happened to me, I look and can for the most part act “normal”- whatever that is. But in truth, I have trouble remembering previous conversations.
What was easy for me in the past takes far more of my energy than it used to. I find it is difficult to follow a conversation in a group. There is too much information for me to take in at one time. Sometimes in a conversation with several people, it exhausts me, I lose my place, and end up not trying to carry on and be a part of the conversation- it’s just too much for my brain to process. I just give up. I may experience “flooding” where my brain cannot take in so much information at one time. People in the conversation may notice I get quiet. They may think that I disagree with them or don’t like the topic. In truth, I may have lost track of the conversation and have no idea what the topic is.
Things that were easy for me in the past are difficult for me now. For example, recently my sister sent me a text asking me to bring two side dishes to a party to celebrate my Dad’s birthday, I don’t remember having a conversation about it at all. I looked back at my texts and found a message from her. In the past, this would be something I would remember and follow up on. Now, I have no memory of the subject at all.
There are ways for others to help those of us with Autoimmune Encephalitis become more comfortable in these situations. So, for family members and friends of those with AE these tips may be helpful.
1. When you start a conversation about plans previously made, talk about the previous discussion that was held. Help by cueing the person. For example, you may say “I messaged you before about dinner on Friday the 12th and wanted to make sure you were still available.” That reassures me that I did have a conversation about it in the past and reminds me of the topic and date. It also allows me a chance to confirm it.
2. If you are asking me to do something, refer back to what had previously happened and provide contact information if you have it, for example, “Last year for the block party you scheduled the Police department to come and register bikes, can you do that again this year? if you can, I will send you the contact information, Let me know by Monday the 8th”
3. If we have made plans, contact me several days or up to a week before to confirm, for example, “I have on my calendar that we were going to the movies on Friday the 10th at 7 pm, will that still work for you?”
4. If we are going someplace where there will be people I may have only met once before, take the time to reintroduce me to them. My husband will usually tell me, “you met them before at the game, but this is John and Mary”
5. When my husband leaves for work and I am still asleep, he leaves a note telling me that he left for work. He knows that if I am not aware, I won’t be sure of the day of the week and may look around the house for him and be anxious about where he is.
Letting family and loved ones know that incorporating these types of supports helps us remain social and successful is truly appreciated. It can keep us from becoming overwhelmed or “shutting down” and allows us to participate fully with more confidence. Trying to stay socially involved is important. Taking a little extra time to do these things will help us to recall previous discussions and allow us to feel more comfortable.
As time goes on, and friends and family learn the types of difficulties their loved one is experiencing, it will be easier to anticipate situations that they may have trouble managing. Coming up with solutions by troubleshooting these situations is the best support you can provide.
Your generous Donationsallow IAES to continue our important work and save lives!
Become an Advocate by sharing your story. It may result in accurate diagnosis for someone suffering right now who is yet to be correctly identified. Submit your story with two photos to IAES@autoimmune-encephalitis.org
Our website is not a substitute for independent professional medical advice. Nothing contained on our website is intended to be used as medical advice. No content is intended to be used to diagnose, treat, cure or prevent any disease, nor should it be used for therapeutic purposes or as a substitute for your own health professional's advice. Although THE INTERNATIONAL AUTOIMMUNE ENCEPHALITIS SOCIETY provides a great deal of information about AUTOIMMUNE ENCEPHALITIS, all content is provided for informational purposes only. The International Autoimmune Encephalitis Society cannot provide medical advice.
International Autoimmune Encephalitis Society is a charitable non-profit 501(c)(3) organization founded in 2016 by Tabitha Andrews Orth, Gene Desotell and Anji Hogan-Fesler. Tax ID# 81-3752344. Donations raised directly supports research, patients, families and caregivers impacted by autoimmune encephalitis and to educating healthcare communities around the world. Financial statement will be made available upon request.
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International Autoimmune Encephalitis Society (IAES), home of the AEWarrior®, is the only Family/Patient-centered organization that assists members from getting a diagnosis through to recovery and the many challenges experienced in their journey. Your donations are greatly appreciated and are the direct result of IAES’s ability to develop the first product in the world to address the needs of patients, 
The last two years of my life seem to have disappeared from my memory. Gone. Holidays, weddings, a funeral, birthday parties, Christmas and New Year. Friends and family keep telling me things I’ve done and the way I’ve behaved, some of which are very embarrassing to hear. It’s just not me.
Eventually, I was transferred back to my local hospital and continued to have a wide range of tests, blood samples were taken every morning to be analyzed and, after three more weeks, I was released to go home with a cannular inserted into a vein in my wrist with 24 tablets to be taken during the morning and 12 at night. I also received IVIG treatment to boost my immune system every morning at the local hospital.
What are seizures?
Lawyers have two great fears in life: 1) missing a deadline and 2) getting sick. Missing a deadline is scary and keeps us awake at night, but getting sick is about the worst. A simple cold or the stomach flu can require us to reschedule a deposition which could possibly change the course of the case and other deadlines, and it feels like all the dominos then start to fall. We’re humans, so we’re going to get sick, but we’re also lawyers, so we can plan for everything. Or wait, can we? I am a lawyer and I fell deathly ill while in private practice. It was unexpected, there was no accordingly tailored action plan, and it was worse than I ever could have imagined. In late May 2018, I was diagnosed with autoimmune encephalitis (AE) and it has forever altered the course of my life. My disease is a sneaky assailant. It took my body and it took my mind before I, or anyone around me, could get a serious hold on what was going on.
Grace Harimate, It is world Encephalitis Awareness day today yesterday in NZ time…. as I contemplated sharing these images and my story, my heart was pounding … I wanted to forget but this ordeal you’ll never forget…I was misdiagnosed and mistreated with bipolar taking the wrong medications and wrong treatment for 6 years from 13y to 18y. Spending most of my teenage years in the mental health ward. But so glad I met the most amazing people in those years…..The hard part was to come when I woke up from a two-year coma… I was fully blind for one-year memory loss still tube fed etc.
January-28-2020 | Daria Muir, M.D.
What neither of us knew at the time was that she saved my life. Because I couldn’t find my keys, I went back to the unit I worked on, shortly after that I had a seizure. I was hospitalized and after a few days of testing, I was diagnosed with anti-NMDAR encephalitis. Anti-NMDAR stands for anti-N- methyl-D- asparate receptor encephalitis. It is an autoimmune disease where the body creates antibodies against the NMDA receptors in the brain. The antibodies disrupt normal brain signaling and can cause seizures, memory problems, cognitive issues, speech disorders, neuropsychiatric symptoms as well as other symptoms.
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