The staff at IAES is proud to present to all of you another wonderful article/blog from the amazing team at PennNeuroKnow. Since 2019 IAES has been extremely lucky to be in partnership with the PennNeuroKnow(PNK) team to help us all better understand complex medical issues related to AE and neurology in general. The talented PNK team continues to keep us up-to-date and help clarify the complexities we face each day along our AE journey, and we are eternally grateful! You can find out much more about this stellar group at: https://pennneuroknow.com/
We all suffer from headaches from time to time. For some a headache is a daily medical issue and they can range from mild and slightly bothersome to migraines that put us in bed for a day or more at a time. This wonderful article by Marissa Maroni helps to shed light on the various types of headaches and the biology behind an issue that we all encounter!
Introduction
We all suffer from headaches from time to time. For some a headache is a daily medical issue and they can range from mild and slightly bothersome to migraines that put us in bed for a day or more at a time. This wonderful article by Marissa Maroni helps to shed light on the various types of headaches and the biology behind an issue that we all encounter!
In the news or on your favorite medical drama you may have been startled to see patients are kept awake during brain surgery. If not, we’ve included an example here! Although it feels wild to witness awake surgeries, they’re possible because the brain itself cannot sense any pain. Despite the lack of pain sensed by the brain, most people do experience head pain at some point in their life, including headaches. The deep, throbbing pain, and sometimes nausea, experienced during a headache can be unbearable. But if brains can’t feel, what causes the pain of a headache and how is this treated?
What kinds of headaches are there?
There are three main types of primary headaches, primary meaning the headache is the issue, rather than a symptom from an underlying condition. The three types of primary headaches are:
Tension-type headaches
Tension-type headaches are the most common primary headache and impact over 25% of people globally1. Tension-type headaches are characterized by mild to moderate head pain that feels like a tightening pressure (imagine hands gripped tightly around your head) that affects both sides of the brain, lasting minutes up to several days2.
Migraines
Migraines effect approximately 14% of the global population1. Migraines are characterized as moderate to severe throbbing pain usually on one side of the brain with pain lasting from several hours to 3 days3. Migraines are usually accompanied by various symptoms such as nausea and light and sound sensitivity4.
Cluster Headaches
Cluster headaches affect approximately 0.4% of people5. Cluster headaches are characterized by excruciating pain on one side of the brain usually surrounding the eye that lasts for minutes up to 3 hours5.
How do they start?
Each of the three primary types of headaches vary in their origin. Rather than extensively unpacking each, let’s focus in on migraines. Prior to a migraine starting a person can experience sound and light sensitivity, mood changes, thirst, and yawning among other symptoms. Scientists have used brain imaging prior to the start of migraines to try and understand why do they start in the first place and what could be causing pre-migraine symptoms?
It is theorized that the brainstem, the stalk of your brain that controls breathing and heart rate among other functions, is the generator of migraines6. A brain imaging study found activity in a subregion of the brainstem was associated with the time until the next migraine starts7. Further, a set of researchers from Germany imaged the brain of a migraine patient for 30 consecutive days to understand what events occur in the brain leading up to a migraine8. They found that before and during a migraine there is altered communication between the brainstem and the hypothalamus, a part of the brain important in controlling sleep, hunger, thirst, and more. Additionally, they found increasing activity in the hypothalamus in the time leading up to a migraine.
Scientists have identified critical brain regions that have altered brain activity prior to a migraine, but can any of this explain pre-migraine symptoms? Researchers hypothesize that the increased activity in the hypothalamus could explain pre-migraine symptoms such as yawning and thirst. Interestingly, migraine patients with light sensitivity have increased activation of the occipital cortex, a brain region responsible for vision perception, in comparison to migraine patients who did not experience light sensitivity9. Although the answer is not precise, scientists have identified altered brain signaling that may prime a brain for a migraine attack and identified specific brain regions that can explain pre-migraine symptoms.
Where does the pain come from?
A main piece to the migraine pain puzzle is a group of nerves that carry pain signals from the face to the brain, referred to as trigeminal ganglion. The trigeminal ganglion connect to the blood vessels surrounding your brain and various parts of the brain including the brainstem, hypothalamus, and thalamus (Figure 1). The thalamus is a place for information to be relayed to your cortex. The activation of trigeminal ganglion lead to a cascade of events that have roles in migraine pain. Let’s explore what events occur and how they contribute to migraine pain.
Figure 1. The trigeminal ganglion, in blue, makes connections to the brainstem, thalamus, and hypothalamus. The thalamus relays information to the cortex.
Sensitization of the brain
During a migraine, it is thought that the trigeminal ganglion become sensitized, meaning they can activate and send pain signals in response to nonpainful stimuli (Figure 2)3. Trigeminal ganglion sensitivity causes throbbing head pain, and pain felt when coughing or bending over during a migraine. Even though you are not doing anything to cause this pain, the trigeminal ganglion is sensitized and sending pain signals anyway! The sensitized trigeminal ganglion lead to the activation and sensitization of the brainstem, and thalamus10. Sensitization of the brainstem and thalamus contribute to allodynia, perception of pain by something not normally painful, like a gentle touch or glasses resting on your nose. Collectively, the sensitization of the trigeminal ganglion, brainstem, and thalamus play a critical role in migraine pain.
Figure 2. Three contributors to migraine pain: sensitization, hyperexcitability, and CGRP release.
Hyperexcitability
Hyperexcitability refers to neurons that are more likely to become active and send signals. General hyperexcitability is seen in individuals with migraines and is hypothesized to contribute to sensitization in the brain as there is more activation in pain signaling regions (Figure 2)3. Brain imaging studies identified that during a migraine the brain is hyper-responsive to sensory information3. This hyper-responsiveness is hypothesized to cause light sensitivity during migraines. Interestingly, when scientists examined shared mutations in the genes of migraine patients, they found that many of the mutated genes were important in neuronal signaling, further suggesting a role for hyperexcitability in migraines11.
Neuropeptide release
The activation of the trigeminal ganglion causes the release of neuropeptides. Neuropeptides are small proteins that cause changes in neuronal signaling (oxytocin is a well-known example of a neuropeptide). An important neuropeptide released after trigeminal ganglion activation is calcitonin-gene related peptide (CGRP). CGRP modulates pains signals, mediates inflammation in the brain, and has cardiovascular, functions among other roles 3,12. There is evidence that CGRP initiates and maintains the sensitization of trigeminal ganglion and is involved in signaling between trigeminal nerves3,13. Further, intravenous administration of CGRP triggers a migraine in migraine patients but not in healthy individuals, suggesting CGRP plays a key role in migraines10. Additionally, CGRP causes blood vessels surrounding the brain to dilate, meaning they expand however, the contribution of blood vessel expansion in migraine pain is disputed14.
What are some treatment for migraines?
Scientists have identified several changes in brain function before and during a migraine that contribute to migraine pain. With all this known, how are migraines treated and how do these treatments work?
A popular and effective treatment for migraines during an active attack are triptans. Triptans act on serotonin receptors. Serotonin is a chemical messenger within our brain responsible for a variety of functions, including mood and digestion. When triptans act on serotonin receptors, they inhibit pain neurotransmission in the trigeminal ganglion, inhibit the release of pain-promoting neuropeptides (like CGRP!), and constrict blood vessels15. Given what we know about headaches, this drug works by halting the cascade of events that occur during a migraine including sensitization, hyperexcitability, and neuropeptide release.
Overall, we’ve uncovered changes in brain signaling that occur before and during a migraine, along with a current treatment. Even though the brain itself cannot feel any pain, it plays a critical role in communicating pain to different parts of your body!
References
Stovner, L. J., Hagen, K., Linde, M., & Steiner, T. J. (2022). The global prevalence of headache: an update, with analysis of the influences of methodological factors on prevalence estimates. The journal of headache and pain, 23(1), 1-17.
Ashina, S., Mitsikostas, D. D., Lee, M. J., Yamani, N., Wang, S. J., Messina, R., … & Lipton, R. B. (2021). Tension-type headache. Nature Reviews Disease Primers, 7(1), 1-21.
Dodick, D. W. (2018). A phase‐by‐phase review of migraine pathophysiology. Headache: the journal of head and face pain, 58, 4-16.
Pescador Ruschel MA, De Jesus O. Migraine Headache. 2022 Jul 6. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan–. PMID: 32809622.
Rossi, P., Whelan, J., Craven, A., & De La Torre, E. R. (2016). What is cluster headache? Fact sheet for patients and their families. A publication to mark Cluster Headache Day 2016. Functional Neurology, 31(3), 181.
Puledda, F., Messina, R., & Goadsby, P. J. (2017). An update on migraine: current understanding and future directions. Journal of neurology, 264(9), 2031-2039.
Stankewitz, A., Aderjan, D., Eippert, F., & May, A. (2011). Trigeminal nociceptive transmission in migraineurs predicts migraine attacks. Journal of Neuroscience, 31(6), 1937-1943.
Schulte, L. H., & May, A. (2016). The migraine generator revisited: continuous scanning of the migraine cycle over 30 days and three spontaneous attacks. Brain, 139(7), 1987-1993.
Karsan, N., & Goadsby, P. J. (2018). Biological insights from the premonitory symptoms of migraine. Nature Reviews Neurology, 14(12), 699-710.
Pietrobon, D., & Moskowitz, M. A. (2013). Pathophysiology of migraine. Annual review of physiology, 75, 365-391.
Burstein, R., Noseda, R., & Borsook, D. (2015). Migraine: multiple processes, complex pathophysiology. Journal of Neuroscience, 35(17), 6619-6629.
Russo, A. F. (2015). Calcitonin gene-related peptide (CGRP): a new target for migraine. Annual review of pharmacology and toxicology, 55, 533.
Iyengar, S., Johnson, K. W., Ossipov, M. H., & Aurora, S. K. (2019). CGRP and the trigeminal system in migraine. Headache: The Journal of Head and Face Pain, 59(5), 659-681.
Buture, A., Gooriah, R., Nimeri, R., & Ahmed, F. (2016). Current understanding on pain mechanism in migraine and cluster headache. Anesthesiology and Pain Medicine, 6(3).
Johnston, M. M., & Rapoport, A. M. (2010). Triptans for the management of migraine. Drugs, 70(12), 1505-1518.
Your generous Donationsallow IAES to continue our important work and save lives!
On June 16 th, 2022, Tabitha Orth, President and Founder of International Autoimmune Encephalitis Society officially became the 7,315 th “point of light”. Recognized for the volunteer work she and IAES has done to spark change and improve the world for those touched by Autoimmune Encephalitis. The award was founded by President George H.W. Bush in 1990.
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.
February 22, 2023 | byCatrina Hacker, PennNeuroKnow and IAES Collaboration
A message from IAES Blog Staff:
The staff at IAES is proud to present to all of you another wonderful article/blog from the amazing team at PennNeuroKnow. Since 2019 IAES has been extremely lucky to be in partnership with the PennNeuroKnow(PNK) team to help us all better understand complex medical issues related to AE and neurology in general. The talented PNK team continues to keep us up-to-date and help clarify the complexities we face each day along our AE journey, and we are eternally grateful! You can find out much more about this stellar group at: https://pennneuroknow.com/
As we wind up AE Awareness month 2023, I, for one, am grateful. Grateful for another year of stellar webinars and more information. For all the AE Warriors and our caregivers, we have a very optimistic future. As you have heard before, our road to recovery is no sprint, but it is a marathon we can and will complete. We receive questions all the time regarding the speed at which research proceeds and treatments are approved. And this is tough because although we know this is a marathon, we all truly want things to proceed much quicker. Catrina Hacker, a member of the amazing PNK team has done a wonderful job explaining the process. So, as I have heard said to me what seems like a million times, “trust the process” and we hope you enjoy this blog!
~Fellow Warrior and Editor-in-Chief, Jeri Gore
Introduction
When you or someone you love is diagnosed with a disease like autoimmune encephalitis, the seemingly slow pace at which research progresses can feel frustrating. It’s hard to watch loved ones suffer while wondering why someone hasn’t used their knowledge and resources to find a solution that will make them feel better. In this post I will walk you through why the pace of research on diseases like autoimmune encephalitis can seem slow and what this means for scientific progress toward understanding autoimmune encephalitis.
The human body still has a lot of uncharted territory for biologists
One of the key reasons that biomedical research seems to progress slowly is that there is so much that we still don’t know. Our quest to understand the human body is much like the quest that European explorers once took to uncover the world beyond Western European countries: sometimes clumsy and a centuries-long process. Christopher Columbus’s crew famously stumbled upon North America on their way to India, and some of the earliest world maps were comically inaccurate by today’s standards (Figure 1 left). But over time the explorers made more observations and built new tools that ultimately led to the incredibly accurate and useful world maps that we have today (Figure 1 right).
Figure 1. Left: A world map generated in 1583. A lot of the general organization of the world has been figured out, but we now know that the proportions and specific shapes of individual continents aren’t correct. Right: A modern world map that shows how much our understanding of the organization of the world has grown in the last 400 years with detailed information about elevation across all 7 continents.
Today, biologists are still in the part of the journey where they’re constantly learning new things and updating their maps. Many biological discoveries still feel like the lucky discovery of the Americas by the Nina, Pinta, and Santa Maria. Making things even more difficult, the uncharted territory that biologists want to understand is even more complicated than the stable land masses of continents. Imagine trying to build a map of the world if small chunks of land moved around and interacted with each other in complicated ways. Now imagine that each explorer had to study a slightly different version of the world with small differences that made it unique, but that had the same general layout. That is the size of the challenge that biologists face when studying the human body.
The challenges of mapmaking for biologists go beyond just the fact that components of the maps move and interact. Biologists also have to build maps at different scales and understand how they relate to one another. Consider understanding the brain as an example. Some neuroscientists study how molecules inside individual brain cells work, others study how small groups of cells connect and send signals between each other, others study how large groups of cells send signals across the brain, and still others study how these signals relate to someone’s behavior or symptoms. Even neuroscientists studying things at the same scale often use different tools that make relating their discoveries to someone else’s challenging. As neuroscientists build maps at each of these levels it’s not always obvious how each map relates to the others and connecting the maps can be just as difficult as building them.
Diseases like autoimmune encephalitis can be hard to categorize and diagnose
Understanding how a healthy human body works is hard enough but extending that understanding to figure out how to treat and cure diseases is even more complicated. When it comes to diseases, many different things can go wrong but produce the same symptoms. And oftentimes when one thing goes wrong, it causes a cascade of other things to go wrong as well. This makes it difficult to pinpoint exactly what went wrong first to try to target that for treatment.
One thing this diversity can make difficult is deciding which patients to group together and which to consider separately. Should researchers group patients by their symptoms (e.g., fatigue, motor deficits, headaches) or by biological markers (e.g., testing for things in the blood or cerebrospinal fluid)? * Scientists’ answer to that question is constantly evolving as they learn more about patients with different kinds of autoimmune encephalitis. Until they know enough to separate subgroups of patients, it can be difficult to see through the diversity of symptoms and biological markers toward a clear understanding of exactly what’s going on.
All of these things only become more difficult the rarer a disease is. The more patients with a certain disease that can be studied, the more data points scientists have to work with. This can give them a better sense of the big picture, despite variability between individual patients. This is why the subtypes of autoimmune encephalitis that are most common, like Anti-NMDAR encephalitis, tend to be better understood than rarer subtypes. When there are more diagnosed patients, the disease is easier to study.
*For a deeper dive into this issue, Penn NeuroKnow writer, Margaret Gardner, wrote about how the same problem impacts our ability to study psychiatric disorders in this PNK article.
Rigorous science can’t be rushed
There are also practical components of how research is conducted that contribute to its slow and steady pace. Research needs to be funded and that is typically done through federal grants from organizations like the National Institute of Health (NIH). Grant funding is competitive, and researchers can spend months working on a proposal before submitting a grant. Once submitted, the grant undergoes rigorous review by other scientists. These reviewers are looking to fund science that they think will be successful, so this means that the best proposals aim to take small and manageable steps in our understanding based on past research. After review, many grants are rejected. So, scientists often have to shake off the disappointment, consider the reviewer feedback, and write an updated proposal. And, as it turns out, getting funding is only half the battle. Once a grant is funded and the project can begin, it takes time to train students and lab workers in the skills needed to conduct the research. Sometimes scientists even have to invent new technology to collect or analyze their data because they’re trying to do something that’s never been done before.
Once scientists have their first set of results, these results often lead to new questions that need to be answered. So, scientists must do many follow-up experiments to understand what’s going on before they can feel confident adding their new discovery to the map of the human body. Once they think they know what’s going on, they then need to replicate their results several times to be sure that what they’re studying is generally true and not specific to whatever patient, animal, or dish of cells they ran their first experiment on. After that scientists will spend months putting their results together into a paper which is then reviewed by other scientists who might ask for more experiments or analyses to make their results more convincing. Finally, the paper is published, and that project can be considered complete. A lot of biomedical research is done by first studying cells in a dish, then studying animal models, and then testing treatments in humans. Each step of this process requires scientists to go through the same process of getting funding, verifying their results, and eventually publishing their work.
While all of these steps contribute to the seemingly slow pace of science, they’re also beneficial to scientific progress. Doing many follow-up experiments, replicating results, and incorporating feedback from other scientists means that once a paper is published scientists can be pretty sure that everything in the paper is accurate. This is important because if scientists couldn’t believe most things that are published then they wouldn’t know what foundation to build on when they design new experiments. Such rigorous requirements for publishing research also help to keep patients safe. Ultimately, the goal is that everything we learn from these papers can be used to develop a treatment or a cure for a disease, which means using that knowledge to help human patients. Once scientists know enough to think about possible treatments, scientists and doctors work together to test these treatments in human patients through a process called clinical trials. Doctors and scientists need to be certain of as much as they can so that those treatments are safe.
Concluding Thoughts
While there’s plenty left to learn about autoimmune encephalitis and thinking about that can feel daunting, it’s important to celebrate that we’ve learned a lot already. Successful treatments that work for many people have already been developed, and treatments are only getting better. An increasing understanding of what autoimmune encephalitis is and how to treat it has also led to the creation of research centers, like the Center of Autoimmune Neurology at the University of Pennsylvania, that make researching the disease and connecting patients and doctors easier. Centralized organizations like the International Autoimmune Encephalitis Society also help raise awareness about these issues and facilitate connections between patients, doctors, and researchers that continue to push our understanding forward.
Altogether, there are a lot of reasons to feel optimistic about the future and to trust in the system of slow and steady scientific research that has already delivered trustworthy, safe treatment options.
Your generous Donationsallow IAES to continue our important work and save lives!
On June 16 th, 2022, Tabitha Orth, President and Founder of International Autoimmune Encephalitis Society officially became the 7,315 th “point of light”. Recognized for the volunteer work she and IAES has done to spark change and improve the world for those touched by Autoimmune Encephalitis. The award was founded by President George H.W. Bush in 1990.
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.
My letter to Santa. ATTENTION: YULETIDE BUREAU WISH DEPARTMENT
Dear Santa, As you know, I have given great thought to my Christmas wish this year. I hope I have made your ‘NICE LIST”, as my wish is in the form of a favor.
Since I am awake, due to insomnia from the IV Solumedrol infusion I received yesterday afternoon, I thought it was a good time to write you. I guess I didn’t need to tell you that, since you see me when I am sleeping, and you know when I am awake. LOL:)
Sometimes the lessons we need to learn to grow our soul and faith come in the most unexpected forms. I have realized the truth of this and am doing my best to rely on my faith, to celebrate the love and support I receive and do my best to face my adversity.
Santa, I have to be totally naked in my honesty here. As Head Elf, embodied with the Spirit of -now here’s my word finding problem rearing its head… It means to love without qualifying or judging. I can’t remember how to say it Santa, but you get me. How could anyone ever imagine they would get a disease where your immune system attacks your brain?!
I mean if my brain isn’t working right, nothing works right. That’s a hard thing Santa. We are talking TOUGH challenge here.
Santa, you know this. You have been watching. I don’t have to explain because you have lived it with me. Yeah, I’m totally on the “NICE LIST”.
Sorry, attention span problems, back to my favor. But… I have practiced daily random acts of kindness for many years…attention span problems again and paranoia I might not make the cut for that ‘Nice List’.
Santa, this disease has created personality changes that are not the heart of me. It has taken ME away before with episodes of psychosis twice now. I am inside. In my heart, buried deep, I am ME. People were not able to see ME when my brain disease flared in this way, but YOU could! Sorry, I will try to stay on topic. Attention Span problems, but YOU know this.
Okay, I forgot what I was going to say… LOL. Wait, I’ll reread this and write my main point on a sticky note so I can remember my wish. Why am I telling you that? YOU see me. YOU realize everything. Ok. Wait just one minute for me Santa. Yes. I am back. Got it. My Christmas Wish. (That is what I wrote on the sticky note. Oops, sorry, forgot. Don’t need to tell you that.)
I am having a problem with worry for my future. I have now faced FEAR. I have stared it down. I have survived. I get scared sometimes. YOU know I do. My faith and spiritual beliefs sustain me; through them, I draw my courage and do my best to surrender my fear.
This brings me to that favor I mentioned. My Christmas Wish. Gosh, Santa, I need your help.
By the way, Jim says guys like peanut butter cookies and oatmeal raisin the best, so we will be leaving those out in their usual place by the Cocoa. Feel free to use the copper pot I leave out for you to warm up your Cocoa in case you find yourself running late. Oh, the carrots for the Reindeer are grown by local farmers- I am adding some lovely fresh pears this year… But, you know that too… Sorry….. What was I going to say? Oh, right! My Christmas Wish:)
You’ll find an envelope by your nighttime snack. I’ve enclosed all my fears and worries inside. Could you kindly take them from me? That is my Christmas Wish.
And when you take your leave, by the way, I LOVE that time suspension magic you do- very cool!
When your laughter rings out within and around our home, can you add a bit of Christmas Spirit Magic to infuse your laughter, Joy, and that kind of love I can’t remember the name of …within our home, our hearts and my brain where my fears and worries once were? By adding your love and laughter to mine Santa, well, that’s a powerful infusion. Exactly what is needed to receive the appreciation of each day.
My family and I laugh a lot Santa. YOU know. My laughter helps my husband, Jim and our son, Matthew. Their laughter helps me. And so, it goes….
P.S. Should you find other letters written by people with Autoimmune Encephalitis, whether they be drawings by children, a single word, or simply the breath of fear blown inside an envelope and sealed, my wish is that you take these too and leave your laughter.
Oh, make yourself at home as long as you would like Santa. The weather across the Northern Hemisphere is projected to be quite cold. There are extra blankets in the hall closet. Help yourself. When you are working your way across the Southern Hemisphere and get to Sarah’s house in New Zealand since it is Summer there and you won’t need them any longer, you can leave the blankets with her and she’ll get them back to me on her next visit;) Pleasant trip and God speed. Best Wishes, Tabitha
(Originally written December 17, 2014)
IAES invites you to spread awareness of Autoimmune Encephalitis by sharing this delightful musical spoof utilizing the classic holiday music from ‘Rudolf the Red-Nosed Reindeer’. Learn who identified the most common type of autoimmune encephalitis of them all and where that magical moment occurred.
Your generous Donations allow IAES to continue our important work and save lives!
International Autoimmune Encephalitis Society (IAES) is a Family/Patient-centered organization that assists members from getting a diagnosis through to recovery and the many challenges experienced in their journey.
Driven by the knowledge that “Education is Power”, International Autoimmune Encephalitis Society manages an educational support group for patients diagnosed with Autoimmune Encephalitis and their loved ones, empowering them to be strong self-advocates and advocates that will lead them to best outcomes and recovery. We are the premier organization leading in these vital roles.
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
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 those 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.
My letter to Santa. ATTENTION: YULETIDE BUREAU WISH DEPARTMENT
Dear Santa, As you know, I have given great thought to my Christmas wish this year. I hope I have made your ‘NICE LIST”, as my wish is in the form of a favor.
Since I am awake, due to insomnia from the IV Solumedrol infusion I received yesterday afternoon, I thought it was a good time to write you. I guess I didn’t need to tell you that, since you see me when I am sleeping, and you know when I am awake. LOL:)
Sometimes the lessons we need to learn to grow our soul and faith come in the most unexpected forms. I have realized the truth of this and am doing my best to rely on my faith, to celebrate the love and support I receive and do my best to face my adversity.
Santa, I have to be totally naked in my honesty here. As Head Elf, embodied with the Spirit of -now here’s my word finding problem rearing its head… It means to love without qualifying or judging. I can’t remember how to say it Santa, but you get me. How could anyone ever imagine they would get a disease where your immune system attacks your brain?!
I mean if my brain isn’t working right, nothing works right. That’s a hard thing Santa. We are talking TOUGH challenge here.
Santa, you know this. You have been watching. I don’t have to explain because you have lived it with me. Yeah, I’m totally on the “NICE LIST”.
Sorry, attention span problems, back to my favor. But… I have practiced daily random acts of kindness for many years…attention span problems again and paranoia I might not make the cut for that ‘Nice List’.
Santa, this disease has created personality changes that are not the heart of me. It has taken ME away before with episodes of psychosis twice now. I am inside. In my heart, buried deep, I am ME. People were not able to see ME when my brain disease flared in this way, but YOU could! Sorry, I will try to stay on topic. Attention Span problems, but YOU know this.
Okay, I forgot what I was going to say… LOL. Wait, I’ll reread this and write my main point on a sticky note so I can remember my wish. Why am I telling you that? YOU see me. YOU realize everything. Ok. Wait just one minute for me Santa. Yes. I am back. Got it. My Christmas Wish. (That is what I wrote on the sticky note. Oops, sorry, forgot. Don’t need to tell you that.)
I am having a problem with worry for my future. I have now faced FEAR. I have stared it down. I have survived. I get scared sometimes. YOU know I do. My faith and spiritual beliefs sustain me; through them, I draw my courage and do my best to surrender my fear.
This brings me to that favor I mentioned. My Christmas Wish. Gosh, Santa, I need your help.
By the way, Jim says guys like peanut butter cookies and oatmeal raisin the best, so we will be leaving those out in their usual place by the Cocoa. Feel free to use the copper pot I leave out for you to warm up your Cocoa in case you find yourself running late. Oh, the carrots for the Reindeer are grown by local farmers- I am adding some lovely fresh pears this year… But, you know that too… Sorry….. What was I going to say? Oh, right! My Christmas Wish:)
You’ll find an envelope by your nighttime snack. I’ve enclosed all my fears and worries inside. Could you kindly take them from me? That is my Christmas Wish.
And when you take your leave, by the way, I LOVE that time suspension magic you do- very cool!
When your laughter rings out within and around our home, can you add a bit of Christmas Spirit Magic to infuse your laughter, Joy, and that kind of love I can’t remember the name of …within our home, our hearts and my brain where my fears and worries once were? By adding your love and laughter to mine Santa, well, that’s a powerful infusion. Exactly what is needed to receive the appreciation of each day.
My family and I laugh a lot Santa. YOU know. My laughter helps my husband, Jim and our son, Matthew. Their laughter helps me. And so, it goes….
P.S. Should you find other letters written by people with Autoimmune Encephalitis, whether they be drawings by children, a single word, or simply the breath of fear blown inside an envelope and sealed, my wish is that you take these too and leave your laughter.
Oh, make yourself at home as long as you would like Santa. The weather across the Northern Hemisphere is projected to be quite cold. There are extra blankets in the hall closet. Help yourself. When you are working your way across the Southern Hemisphere and get to Sarah’s house in New Zealand since it is Summer there and you won’t need them any longer, you can leave the blankets with her and she’ll get them back to me on her next visit;) Pleasant trip and God speed. Best Wishes, Tabitha
(Originally written December 17, 2014)
IAES invites you to spread awareness of Autoimmune Encephalitis by sharing this delightful musical spoof utilizing the classic holiday music from ‘Rudolf the Red-Nosed Reindeer’. Learn who identified the most common type of autoimmune encephalitis of them all and where that magical moment occurred.
Your generous Donations allow IAES to continue our important work and save lives!
International Autoimmune Encephalitis Society (IAES) is a Family/Patient-centered organization that assists members from getting a diagnosis through to recovery and the many challenges experienced in their journey.
Driven by the knowledge that “Education is Power”, International Autoimmune Encephalitis Society manages an educational support group for patients diagnosed with Autoimmune Encephalitis and their loved ones, empowering them to be strong self-advocates and advocates that will lead them to best outcomes and recovery. We are the premier organization leading in these vital roles.
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
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 those 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.
My letter to Santa. ATTENTION: YULETIDE BUREAU WISH DEPARTMENT
Dear Santa, As you know, I have given great thought to my Christmas wish this year. I hope I have made your ‘NICE LIST”, as my wish is in the form of a favor.
Since I am awake, due to insomnia from the IV Solumedrol infusion I received yesterday afternoon, I thought it was a good time to write you. I guess I didn’t need to tell you that, since you see me when I am sleeping, and you know when I am awake. LOL:)
Sometimes the lessons we need to learn to grow our soul and faith come in the most unexpected forms. I have realized the truth of this and am doing my best to rely on my faith, to celebrate the love and support I receive and do my best to face my adversity.
Santa, I have to be totally naked in my honesty here. As Head Elf, embodied with the Spirit of -now here’s my word finding problem rearing its head… It means to love without qualifying or judging. I can’t remember how to say it Santa, but you get me. How could anyone ever imagine they would get a disease where your immune system attacks your brain?!
I mean if my brain isn’t working right, nothing works right. That’s a hard thing Santa. We are talking TOUGH challenge here.
Santa, you know this. You have been watching. I don’t have to explain because you have lived it with me. Yeah, I’m totally on the “NICE LIST”.
Sorry, attention span problems, back to my favor. But… I have practiced daily random acts of kindness for many years…attention span problems again and paranoia I might not make the cut for that ‘Nice List’.
Santa, this disease has created personality changes that are not the heart of me. It has taken ME away before with episodes of psychosis twice now. I am inside. In my heart, buried deep, I am ME. People were not able to see ME when my brain disease flared in this way, but YOU could! Sorry, I will try to stay on topic. Attention Span problems, but YOU know this.
Okay, I forgot what I was going to say… LOL. Wait, I’ll reread this and write my main point on a sticky note so I can remember my wish. Why am I telling you that? YOU see me. YOU realize everything. Ok. Wait just one minute for me Santa. Yes. I am back. Got it. My Christmas Wish. (That is what I wrote on the sticky note. Oops, sorry, forgot. Don’t need to tell you that.)
I am having a problem with worry for my future. I have now faced FEAR. I have stared it down. I have survived. I get scared sometimes. YOU know I do. My faith and spiritual beliefs sustain me; through them, I draw my courage and do my best to surrender my fear.
This brings me to that favor I mentioned. My Christmas Wish. Gosh, Santa, I need your help.
By the way, Jim says guys like peanut butter cookies and oatmeal raisin the best, so we will be leaving those out in their usual place by the Cocoa. Feel free to use the copper pot I leave out for you to warm up your Cocoa in case you find yourself running late. Oh, the carrots for the Reindeer are grown by local farmers- I am adding some lovely fresh pears this year… But, you know that too… Sorry….. What was I going to say? Oh, right! My Christmas Wish:)
You’ll find an envelope by your nighttime snack. I’ve enclosed all my fears and worries inside. Could you kindly take them from me? That is my Christmas Wish.
And when you take your leave, by the way, I LOVE that time suspension magic you do- very cool!
When your laughter rings out within and around our home, can you add a bit of Christmas Spirit Magic to infuse your laughter, Joy, and that kind of love I can’t remember the name of …within our home, our hearts and my brain where my fears and worries once were? By adding your love and laughter to mine Santa, well, that’s a powerful infusion. Exactly what is needed to receive the appreciation of each day.
My family and I laugh a lot Santa. YOU know. My laughter helps my husband, Jim and our son, Matthew. Their laughter helps me. And so, it goes….
P.S. Should you find other letters written by people with Autoimmune Encephalitis, whether they be drawings by children, a single word, or simply the breath of fear blown inside an envelope and sealed, my wish is that you take these too and leave your laughter.
Oh, make yourself at home as long as you would like Santa. The weather across the Northern Hemisphere is projected to be quite cold. There are extra blankets in the hall closet. Help yourself. When you are working your way across the Southern Hemisphere and get to Sarah’s house in New Zealand since it is Summer there and you won’t need them any longer, you can leave the blankets with her and she’ll get them back to me on her next visit;) Pleasant trip and God speed. Best Wishes, Tabitha
(Originally written December 17, 2014)
IAES invites you to spread awareness of Autoimmune Encephalitis by sharing this delightful musical spoof utilizing the classic holiday music from ‘Rudolf the Red-Nosed Reindeer’. Learn who identified the most common type of autoimmune encephalitis of them all and where that magical moment occurred.
Your generous Donations allow IAES to continue our important work and save lives!
International Autoimmune Encephalitis Society (IAES) is a Family/Patient-centered organization that assists members from getting a diagnosis through to recovery and the many challenges experienced in their journey.
Driven by the knowledge that “Education is Power”, International Autoimmune Encephalitis Society manages an educational support group for patients diagnosed with Autoimmune Encephalitis and their loved ones, empowering them to be strong self-advocates and advocates that will lead them to best outcomes and recovery. We are the premier organization leading in these vital roles.
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
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 those 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.
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.
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
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
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
My letter to Santa. ATTENTION: YULETIDE BUREAU WISH DEPARTMENT
Dear Santa, As you know, I have given great thought to my Christmas wish this year. I hope I have made your ‘NICE LIST”, as my wish is in the form of a favor.
Since I am awake, due to insomnia from the IV Solumedrol infusion I received yesterday afternoon, I thought it was a good time to write you. I guess I didn’t need to tell you that, since you see me when I am sleeping, and you know when I am awake. LOL:)
Sometimes the lessons we need to learn to grow our soul and faith come in the most unexpected forms. I have realized the truth of this and am doing my best to rely on my faith, to celebrate the love and support I receive and do my best to face my adversity.
Santa, I have to be totally naked in my honesty here. As Head Elf, embodied with the Spirit of -now here’s my word finding problem rearing its head… It means to love without qualifying or judging. I can’t remember how to say it Santa, but you get me. How could anyone ever imagine they would get a disease where your immune system attacks your brain?!
I mean if my brain isn’t working right, nothing works right. That’s a hard thing Santa. We are talking TOUGH challenge here.
Santa, you know this. You have been watching. I don’t have to explain because you have lived it with me. Yeah, I’m totally on the “NICE LIST”.
Sorry, attention span problems, back to my favor. But… I have practiced daily random acts of kindness for many years…attention span problems again and paranoia I might not make the cut for that ‘Nice List’.
Santa, this disease has created personality changes that are not the heart of me. It has taken ME away before with episodes of psychosis twice now. I am inside. In my heart, buried deep, I am ME. People were not able to see ME when my brain disease flared in this way, but YOU could! Sorry, I will try to stay on topic. Attention Span problems, but YOU know this.
Okay, I forgot what I was going to say… LOL. Wait, I’ll reread this and write my main point on a sticky note so I can remember my wish. Why am I telling you that? YOU see me. YOU realize everything. Ok. Wait just one minute for me Santa. Yes. I am back. Got it. My Christmas Wish. (That is what I wrote on the sticky note. Oops, sorry, forgot. Don’t need to tell you that.)
I am having a problem with worry for my future. I have now faced FEAR. I have stared it down. I have survived. I get scared sometimes. YOU know I do. My faith and spiritual beliefs sustain me; through them, I draw my courage and do my best to surrender my fear.
This brings me to that favor I mentioned. My Christmas Wish. Gosh, Santa, I need your help.
By the way, Jim says guys like peanut butter cookies and oatmeal raisin the best, so we will be leaving those out in their usual place by the Cocoa. Feel free to use the copper pot I leave out for you to warm up your Cocoa in case you find yourself running late. Oh, the carrots for the Reindeer are grown by local farmers- I am adding some lovely fresh pears this year… But, you know that too… Sorry….. What was I going to say? Oh, right! My Christmas Wish:)
You’ll find an envelope by your nighttime snack. I’ve enclosed all my fears and worries inside. Could you kindly take them from me? That is my Christmas Wish.
And when you take your leave, by the way, I LOVE that time suspension magic you do- very cool!
When your laughter rings out within and around our home, can you add a bit of Christmas Spirit Magic to infuse your laughter, Joy, and that kind of love I can’t remember the name of …within our home, our hearts and my brain where my fears and worries once were? By adding your love and laughter to mine Santa, well, that’s a powerful infusion. Exactly what is needed to receive the appreciation of each day.
My family and I laugh a lot Santa. YOU know. My laughter helps my husband, Jim and our son, Matthew. Their laughter helps me. And so, it goes….
P.S. Should you find other letters written by people with Autoimmune Encephalitis, whether they be drawings by children, a single word, or simply the breath of fear blown inside an envelope and sealed, my wish is that you take these too and leave your laughter.
Oh, make yourself at home as long as you would like Santa. The weather across the Northern Hemisphere is projected to be quite cold. There are extra blankets in the hall closet. Help yourself. When you are working your way across the Southern Hemisphere and get to Sarah’s house in New Zealand since it is Summer there and you won’t need them any longer, you can leave the blankets with her and she’ll get them back to me on her next visit;) Pleasant trip and God speed. Best Wishes, Tabitha
(Originally written December 17, 2014)
IAES invites you to spread awareness of Autoimmune Encephalitis by sharing this delightful musical spoof utilizing the classic holiday music from ‘Rudolf the Red-Nosed Reindeer’. Learn who identified the most common type of autoimmune encephalitis of them all and where that magical moment occurred.
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International Autoimmune Encephalitis Society (IAES) is a Family/Patient-centered organization that assists members from getting a diagnosis through to recovery and the many challenges experienced in their journey.
Driven by the knowledge that “Education is Power”, International Autoimmune Encephalitis Society manages an educational support group for patients diagnosed with Autoimmune Encephalitis and their loved ones, empowering them to be strong self-advocates and advocates that will lead them to best outcomes and recovery. We are the premier organization leading in these vital roles.
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
Autoimmune encephalitis (AE) is the name for a group of conditions that occur when the body’s immune system mistakes its own healthy brain cells for invaders, leading to brain inflammation that ultimately triggers a number of other symptoms. Normally, the body’s immune system has only limited access to the brain, as it is protected by the blood-brain barrier (BBB). When this barrier is healthy, it can prevent an immune system attack by blocking immune cells and antibodies targeting brain cells from actually entering the brain. Like any fortress, however, the BBB isn’t completely impenetrable. Given that AE symptoms occur when immune cells or antibodies manage to cross the BBB, researchers think that the weakening of this barrier plays a critical role in AE and may even be a target for future therapies to reduce or prevent AE symptoms. But what causes the BBB to weaken, allowing cells, antibodies, and other molecules to invade the brain?
The blood-brain barrier: gatekeeper of the brain
Before discussing how the BBB becomes impaired, we need to understand how the healthy BBB functions. The BBB is often referred to as a “gateway”, made up of tightly joined endothelial cells that surround the blood vessels in the brain and spinal cord1. Outside of the brain, the endothelial cells lining blood vessels have small spaces between them, allowing for the exchange of substances between the blood and the surrounding tissue. However, the endothelial cells of the BBB are connected to each other by proteins called tight junction proteins, which squeeze the cells tightly together, blocking larger cells and molecules from freely flowing between the blood supply and the brain (Figure 1).
Figure 1: The blood-brain barrier is made up of endothelial cells that are tightly connected to each other by tight junction proteins (purple). These tight connections prevent unwanted substances from traveling between the blood and the brain. Different types of transporter proteins (yellow & blue) shuttle only certain types of molecules between the blood and brain.
The BBB is selectively permeable, meaning it allows only certain substances to enter and leave the brain. One way that molecules can cross the BBB is by endocytosis, a process where the endothelial cells uses its cell membrane to take in a molecule on one side (say, the side facing the blood) and pass it through to the other side (facing the brain) where it is released1. The endothelial cells of the BBB also express a variety of transporter proteins, which actively move molecules between the blood and the brain (Figure 1). Additionally, small, fat-soluble molecules can cross the BBB without any help from endocytosis or transporter proteins, giving the brain access to important nutrients and energy sources1.
BBB permeability changes across the day
The permeability of the BBB is not always the same, however. Research has shown that its permeability actually changes depending on the time of day2. Like many cells in the body, BBB cells are controlled by circadian rhythms, biological processes that cycle roughly every 24 hours. These rhythms are driven by a molecular “clock” within each cell, and cells across the body are synchronized by the “master clock” located in the brain.
What do these rhythms mean for BBB permeability though? Interestingly, research in both flies and mice shows that the amount of hormones, inflammatory proteins, and other molecules that cross from the blood into the brain fluctuates across the day, with peak BBB permeability occurring at night2.
Sleep loss impairs BBB function
Circadian rhythms aren’t the only daily process that affects the integrity of the BBB. Sleep—or more appropriately, lack of sleep—is also known to affect the BBB’s protection of the brain. This relationship between sleep and the BBB is increasingly important as sleep restriction becomes more and more common in our modern society.
Sleep loss is also highly relevant to the AE community. One study found that 73% of AE patients surveyed reported sleep disturbances, including gasping/snoring and insomnia. Even further, patients with AE had decreased total sleep time and increased fragmentation of sleep compared to people without AE3. But how exactly does sleep loss affect the BBB?
Figure 2: After periods of sleep loss, the blood-brain barrier is negatively affected in many ways (left). Inflammatory signaling caused by TNFα and IL-6 increases, leading to the breakdown of tight junction proteins (purple). This causes gaps between endothelial cells, allowing unwanted immune cells and antibodies to enter the brain. After sleep loss, the endothelial cells also make fewer of the transporter proteins (blue and yellow) that are required to shuttle necessary molecules between the brain and blood.
Multiple studies have now shown that sleep restriction weakens the BBB. One reason is due to the increase in inflammatory signaling that results from extended periods of wakefulness. Increases in inflammatory proteins, like TNFα and IL-6, are known to break down the tight junction proteins that keep the endothelial cells tightly joined together2 (Figure 2). Sleep-deprived mice and rats showed decreased numbers of tight junction proteins, leading to increased BBB permeability.
In addition to weakened tight junctions between endothelial cells, sleep loss also increases permeability by enhancing the rate of endocytosis across the BBB2, meaning that the endothelial cells shuttle more molecules from the blood into the brain. Relevant to AE, this increased permeability means that more immune cells and antibodies can enter the brain after sleep loss compared to after a full night’s sleep.
While these results are a bit frightening, there is good news. All of the damage to the BBB caused by sleep loss returns to normal after getting enough sleep! One study found that even an extra 1-2 hours of sleep following sleep loss restored BBB function in most brain areas4. Given even more time to sleep, the BBB throughout the brain returned to normal function5. These results suggest that treating the sleep disorders commonly associated with AE may help strengthen the BBB, increasing the brain’s protection against the immune system’s cells and antibodies and improving long-term outcomes for patients.
The BBB as a treatment target
Given that AE is caused by immune cells and antibodies infiltrating and attacking the brain, researchers are now looking at the BBB as a potential therapeutic target1. Treatments that strengthen the BBB will hopefully reduce the number of immune cells and antibodies that make it into the brain, and may also increase the effectiveness of some AE medications, such as anti-inflammatory drugs or immune-suppressants. Because these AE medications are specifically designed to cross a healthy BBB and access the brain, strengthening a weakened BBB will protect against molecules that aren’t supposed to be in the brain, while still allowing the necessary medication in.
The known circadian effects on BBB permeability can also be used in determining when to give medication that needs to cross the BBB. Medication can be given at the time of day when BBB permeability is highest to increase the amount of drug that makes it into the brain. In fact, this has already been studied with anti-seizure medication in epilepsy. For instance, in both flies and humans, when medication was given at night during peak BBB permeability, it was most effective at controlling seizures6,7.
This new strategy of “chronotherapeutic” dosing schedules has the potential to improve the efficacy of medication in many diseases. By administering drugs when it is easiest for them to enter the brain, doctors may be able to see results at lower doses of the drug, potentially reducing the risk of harmful side effects. As we continue to learn more about the BBB, scientists may identify even more ways to improve BBB health in the many disease states where it is compromised.
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Image References: Figure 1 and 2 created with BioRender.com
References:
Platt MP, Agalliu D, Cutforth T (2017) Hello from the other side: How autoantibodies circumvent the blood-brain barrier in autoimmune encephalitis. Front. Immunol. 8:442. doi: 10.3389/fimmu.2017.00442
Cuddapah VA, Zhang SL, Sehgal A (2019) Regulation of the blood-brain barrier by circadian rhythms and sleep. Trends Neurosci 42(7):500-510. doi: 10.1016/j.tins.2019.05.001
Blattner MS, de Bruin GS, Bucelli RC, Day GS (2019) Sleep disturbances are common in patients with autoimmune encephalitis. J Neurol 266(4):1007-1015. doi: 10.1007/s00415-019-09230-2
Gomex-Gonzalez B, et al. (2013) Rem sleep loss and recovery regulates blood-brain barrier function. Curr. Neurovasc. Res. 10, 197-207
He J, Hsuchou H, He Y, Kastin AJ, Wang Y, &Pan W (2014) Sleep restriction impairs blood-brain barrier function. J Neurosci 34(44)14697-14706. doi: 10.1523/jneurosci.2111-14.2014
Zhang SL, Yue Z, Arnold DM, Artiushin G, Sehgal A (2018) A circadian clock in the blood-brain barrier regulates xenobiotic efflux. Cell 173(1):130-139. doi: 10.1016/j.cell.2018.02.017
Yegnanarayan R, et al. (2006) Chronotherapeutic dose schedule of phenytoin and carbamazepine in epoleptic patients. Chronobiol. Int 23, 1035-1046
When we catch a cold, get an infection, or otherwise become sick, our bodies use a natural defense mechanism called the immune system to fight off what’s attacking us. The immune system has two ways of responding1. The first, called innate immunity, involves physical and chemical barriers like the skin and saliva, as well as many different types of cells that “eat” and destroy whatever is causing the trouble. While this innate response happens very quickly, then the downside is that it’s not very specific, and the immune cells can damage healthy parts of the body while trying to gobble up the foreign invaders. In order to specifically target particular offenders, the body uses its second way of responding: the adaptive immune system. This response can take days or weeks to develop but is also able to remember what the foreign invader looked like, so if it attacks again a targeted reaction can occur faster than the first time. To acquire this immunity against a particular foreign substance, the body uses two types of cells that act in different ways: T cells (which develop in an organ called the thymus, that’s where the “T” comes from) and B cells (which mature in the bone marrow, hence the “B”).
These two cell types are able to attack so specifically because each one recognizes a particular structure, called an antigen, on a foreign substance. For instance, one T cell might recognize a certain part of an influenza virus, while another could recognize a specific part of a bacterium; the same situation also holds true for B cells. The T and B cells travel around between different lymphoid tissues (organs like the spleen, tonsils, and lymph nodes, the last which are spread throughout the body) until they encounter their particular antigen. Once activated by their antigen, the T and B cells leave the lymph tissues and work in different ways to fight off the foreign invader (Figure 1).
Types of T and B cells
T cells come in many varieties, but the two major types are cytotoxic and helper. Cytotoxic T cells (sometimes referred to as CD8+ T cells due to a particular identifier on their surface) travel to the disease site to search for cells that also bear the antigen that activated them, and destroy them. Helper T cells (sometimes referred to as CD4+ T cells), as the name might suggest, help activate other parts of the immune system. There are many subtypes of helper T cells that activate different types of responses; for instance, some promote the cytotoxic T cell response, while others activate B cells. Another kind of CD4+ T cell called regulatory cells actually tells the immune system, not to attack2.
Unlike T cells, B cells do not destroy their target. Instead, once they are activated by their antigen and T helper cells, they mature into plasma cells that produce antibodies, proteins that recognize the same antigen as the B cell. These antibodies essentially enhance the innate immune system and act in several ways, including neutralizing toxins, signaling to other immune cells that a cell should be attacked and destroyed, or activating complement. Complement is a group of proteins (not cells) that make up yet another arm of the immune system. These complement proteins can recruit immune cells or directly kill foreign cells themselves1.
T and B Cells in Autoimmune Encephalitis
So what happens in autoimmune encephalitis (AE)? In this and other autoimmune diseases, the body mistakenly recognizes part of itself as a foreign invader and mounts an attack. Scientists believe that AE starts when a tumor or virus causes proteins from neurons to be exposed to the immune system. The proteins get picked up by immune cells outside the brain that go on to activate T and B cells in lymphoid tissue. These activated cells then make their way into the brain where they cause AE3,4. Which cells are responsible for causing the disease depends on what antigen sets off the immune response.
In cases where the antigen comes from inside a cell, cytotoxic T cells are the culprits. When proteins from inside neurons like Hu, Yo, or Ma2 are the antigens, that usually indicates that the immune system first encountered the proteins in a cancerous tumor, which can express proteins from all sorts of cell types (this cancer association is why these antibodies and diseases are called “onconeural,” or “paraneoplastic”). Cytotoxic T cells fighting the tumor can make their way into the brain and kill neurons5. This cell death is likely part of the reason why patients with these diseases have poor recovery. Antibodies from B cells that have matured into plasma cells can also be produced in response to the tumor, but they do not contribute to AE symptoms6.
Antibodies do have a strong role in producing AE symptoms when the antigen comes from the outside surface of a neuron, like the NMDA receptor for instance. These antibodies can still be formed in reaction to a tumor, but this is less common. Research on NMDAR encephalitis, in particular, has revealed the presence of B cells and antibody-secreting plasma cells in the brain7,8. Because the antibodies have access to the surface proteins they target, they can bind to them and interfere with their function. In the case of NMDAR encephalitis, it’s thought that the antibodies cause the receptors, which normally are exposed to the outside of the cell, to be taken back inside so that they can’t function properly. Once the antibodies are gone the receptors can return to the cell surface, reversing many of the symptoms9. Unlike diseases in which the antibodies target intracellular proteins, in NMDAR encephalitis there are few to no cytotoxic T cells in the brain or neuronal death5,7,8. But while there are little to no cytotoxic T cells, there have been reports of helper T cells around blood vessels in the brain, including one type called Th17 that act to enhance the immune response10.
In other cases of encephalitis with antibodies again a cell surface protein, such as LGI1, CASPR2, or GABA receptors, the precise immune reaction is less certain and in some ways seems to be a little different from NMDAR encephalitis. B cells and plasma cells are still found in the brain, and antibodies also play a major role in causing symptoms5,11. For instance, antibodies against the GABAB receptor block it from functioning, while antibodies against LGI1 can disrupt interactions between proteins and lead to a decrease in AMPA receptors12. The involvement of T cells is unclear and may vary depending on the disease-causing antibody. For example, cytotoxic and helper T cells have been found in the brain of anti-GABAB receptor patients11, while few T cells were found in anti-VGKC-complex patients5. In addition, scientists sometimes observe signs of complement, the protein arm of the immune system that can kill cells5,6. In line with the presence of cytotoxic T cells and complement, neuronal loss is sometimes reported5,13.
Overall, the type of immune response the body produces appears to be dependent on the specific antigen. In general, diseases with antibodies that target intracellular proteins like Hu, Yo, or Ma2 involve cytotoxic T cells that kill neurons. In contrast, diseases with antibodies that target cell surface proteins like NMDAR, LGI1, and GABAR involve B cells in symptom production. In this second category, the role of T cells and complement may vary depending on the particular antigen.
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
References
Parkin, J. & Cohen, B. An overview of the immune system. Lancet357, 1777–1789 (2001).
Corthay, A. How do regulatory T cells work? Scand. J. Immunol.70, 326–336 (2009).
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).
Bien, C. G. et al. Immunopathology of autoantibody-associated encephalitides: Clues for pathogenesis. Brain135, 1622–1638 (2012).
Damato, V., Balint, B., Kienzler, A. K. & Irani, S. R. The clinical features, underlying immunology, and treatment of autoantibody-mediated movement disorders. Mov. Disord.33, 1376–1389 (2018).
Martinez-Hernandez, E. et al. Analysis of complement and plasma cells in the brain of patients with anti-NMDAR encephalitis. Neurology77, 589–593 (2011).
Tüzün, E. et al. Evidence for antibody-mediated pathogenesis in anti-NMDAR encephalitis associated with ovarian teratoma. Acta Neuropathol.118, 737–743 (2009).
Dalmau, J. et al. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol.7, 1091–1098 (2008).
Zeng, C. et al. Th17 cells were recruited and accumulated in the cerebrospinal fluid and correlated with the poor prognosis of anti-NMDAR encephalitis. Acta Biochim. Biophys. Sin. (Shanghai).50, 1266–1273 (2018).
Golombeck, K. S. et al. Evidence of a pathogenic role for CD8 + T cells in anti-GABA B receptor limbic encephalitis. Neurol. Neuroimmunol. NeuroInflammation3, 1–8 (2016).
Dalmau, J. & Graus, F. Antibody-mediated encephalitis. N. Engl. J. Med.378, 840–851 (2018).
Shin, Y.-W. et al. Treatment strategies for autoimmune encephalitis. Ther. Adv. Neurol. Disord.11, 1–19 (2018).
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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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