Select Page
Treatments for Autoimmune Encephalitis

Treatments for Autoimmune Encephalitis

by | Apr 26, 2023 | PennNeuroKnow


April 26, 2023 | by Sophie Liebergall, 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/

——-

Introduction

 

Though it can be challenging for doctors to correctly identify and diagnose autoimmune encephalitis (AE), once patients do indeed receive a proper diagnosis there are treatment options that can go a long way in alleviating their symptoms sending them down the road to recovery. A recent study reports that 94% of patients with AE have significant improvement in or complete resolution of symptoms in the first few years after their diagnosis.1,2  One important key to success is promptly starting treatment which both reduces the likelihood of long-term symptoms and prevents relapses.

The job of your body’s immune system is to find and eliminate invaders, like bacteria and viruses, that may be harmful. But in the case of AE, the immune system mistakes the brain as an invader and mounts an attack, leading to inflammation in the brain.3 This inflammation is what causes the symptoms of AE, like hallucinations, memory problems, and seizures. Therefore, all current medical treatments for AE are aimed at decreasing inflammation.4 But even if the ultimate goal is always to reduce brain inflammation, there may be slight variations in the choice of therapies depending on the type of AE and the patient’s unique medical history.

Physicians divide the treatments for AE into first-line and second-line therapies. First-line therapies are treatments that doctors generally prescribe first when a patient is diagnosed with AE. Second-line therapies are treatments that doctors reach for when the first-line therapies didn’t work, or if there are lingering symptoms following initial improvement with first-line therapies.

In this article, we’ll walk through some of the common treatments for AE, why doctors may or may not choose them for a given patient, and how these treatments are thought to reduce AE symptoms.

First-Line Treatments

Steroids

If you or a loved one has been diagnosed with AE, you’re probably familiar with steroids, the medicine that doctors often use first when treating AE. When many people hear the term “steroids,” they think of Barry Bonds or other professional athletes who have used performance-enhancing drugs to get an edge on the competition. But in reality, “steroids” is an umbrella term used to describe a group of chemicals that share a similar shape. Whereas athletes looking to circumvent the rules use steroids called anabolic steroids, doctors treating AE prescribe steroids called glucocorticoids.4

Though doctors can administer glucocorticoids to a patient as a pill or in an IV, we actually make glucocorticoids naturally in our bodies all the time! Our homemade glucocorticoids are essential for a wide range of our bodily functions – from controlling how our body manages sugars and fats, to telling our brain to be alert to our surroundings, to damping down inflamation.5 When prescribing glucocorticoids to patients with AE, doctors try to take advantage of the anti-inflammatory properties of these chemicals.

How exactly do glucocorticoids put the brakes on inflammation? They act quickly and powerfully at the source of inflammation: the cells of your immune system (Figure 1).5 Once they breach the walls of an immune cell, glucocorticoids enter the nucleus, which serves as the control center of a cell. It’s in the nucleus that the cell writes out the instructions for making the proteins that it needs to mount an immune attack. By breaching this nucleus control center, glucocorticoids can override the machinery that the cell uses to write these instructions. This ultimately prevents the immune cells from causing inflammation.

glucocorticoid mechanism summary V1 500x358 - Treatments for Autoimmune Encephalitis

Figure 1. How do glucocorticoids treat AE? Glucocorticoids enter the nucleus of an immune cell, where they override the messages that the cell writes as it tries to make inflammatory proteins.

 

Unfortunately, glucocorticoids don’t just interfere with the instructions that immune cells use for making inflammatory proteins. They also interfere with the instructions that many other kinds of cells in the body rely on for carrying out their own important functions.6 For example, glucocorticoids can affect the instructions that the cells in your bones use to tell themselves to grow and retain their strength. This can lead to the weakening of your bones, which is a common side effect of glucocorticoids.7 Other side effects include problems with your body’s metabolism, like the redistribution of body fat, as well problems with your skin, like impaired wound healing.6 When patients with AE are first diagnosed, they are often very sick, so very high doses of glucocorticoids may be required to stabilize their condition.8 But as AE symptoms improve, doctors try to slowly reduce the amount of glucocorticoids that a patient is prescribed to prevent some of the harmful and uncomfortable side effects of these powerful medications.

Plasma Exchange (PLEX)

Rather than targeting the inner workings of the immune cells, other treatments for AE target the proteins that are made by the immune cells. One type of protein that immune cells make is called an antibody. Antibodiesselectively stick to invaders and flag them for destruction by other cells in the immune system.9 But in the case of AE, the body accidentally makes antibodies against its own proteins in the brain. When the immune system sees these flags, it mistakenly attacks the healthy brain.

Plasma exchange (PLEX) is a therapy that tries to remove these antibodies that erroneously tell the immune system to attack the brain.10 Antibodies are generally transported in the plasma, which is the liquid-y component of blood. During PLEX therapy, tubes are placed in your veins so that your blood can pass through a machine as it is pumped around your body (Figure 2). This machine acts like a coffee filter, separating the liquid part of your blood (the coffee) from the blood cells (the grounds). Because the liquid part of your blood contains the harmful antibodies, the liquid is discarded and replaced with the plasma of a healthy donor. This healthy plasma is then recombined with your own blood cells that were trapped in the coffee filter, and sent back into your body through another tube.

PLEX summary V2 500x279 - Treatments for Autoimmune Encephalitis

Figure 2. What happens during plasma exchange (PLEX) therapy? Whole blood is removed from the patient’s vein, then separated into its plasma and red blood cell components. The patient’s plasma is discarded and replaced with donor plasma, which is recombined with the patient’s red blood cells and returned to the patient’s blood stream.

 

PLEX is generally safe and effective, and it can be especially useful for patients who are particularly vulnerable to the side effects of glucocorticoids.8 However, a major downside of PLEX is that it requires the placement of the tubes that are used to remove and return the blood to the body for the duration of the treatment. These tubes can be a source of infection or bleeding, and can make it logistically challenging for patients to receive PLEX if they aren’t already in the hospital.

Intravenous Immune Globulin (IVIG)

Intravenous immune globulin (IVIG) is another AE treatment that tries to interfere with the antibodies that mistakenly target a patient’s healthy brain in AE. Our blood contains thousands of different antibodies, most of which are designed to target the foreign invaders that we have encountered during our lifetimes. IVIG is the result of taking the blood of thousands of different people, extracting the antibodies from that blood, and then combining the antibodies of all of the different donors.11 This creates a very concentrated slushy of thousands and thousands of antibodies that target all sorts of different proteins. When IVIG is administered to a patient, these antibodies then enter their bloodstream and circulate with the rest of the patient’s blood.

IVIG summary V1 500x323 - Treatments for Autoimmune Encephalitis

Figure 3. What is intravenous immune globulin (IVIG) therapy? The antibody-containing serum of thousands of donors is combined and then administered to the patient through an IV.

Given that AE is caused by a rogue antibody, it may seem crazy that doctors would give patients many more highly concentrated antibodies to treat AE. But, IVIG is very effective with minimal side effects beyond an increased risk of blood clots in some patients.12 So how does it work? Doctors think that IVIG overwhelms the immune system by flooding it with so many antibodies that the AE-causing antibodies just get swept up in the rush. In other words, the immune system may be so distracted by the onslaught of other antibodies that it forgets about the antibody that was driving the AE symptoms.11

Second-Line Treatments

 

Rituximab

If the first-line therapies don’t provide sufficient relief for a patient with AE, the most common second-line therapy is a drug called rituximab.8 Rituximab, which was initially designed to treat cancer, is, itself, an antibody.13 But, interestingly, its job is to “tag” the cells in the body’s own immune system that make other antibodies. This causes the body’s immune system to kill its own antibody-producing cells, ultimately halting the production of antibodies.

This means that rituximab can stop the immune system from making the harmful brain-targeting autoantibodies that cause AE symptoms. But Rituximab doesn’t just suppress the production of the AE-causing antibodies – it suppresses the production of all antibodies, including those necessary for fighting infections. This can leave patients vulnerable to bacterial and viral invaders that they would normally be able to fight off. Additionally, rituximab is known to cause other side effects like fevers, fatigue, and nausea.13Nevertheless, rituximab has been shown to be an effective at restoring functioning for patients with AE who need additional treatment on top of first-line therapies.14

Cyclophosphamide

Cyclophosphamide is another cancer drug that has been repurposed as a second-line agent in the treatment of AE.8 Cyclophosphamide works by entering the nucleus of a cell and attaching chemical “decorations” to the cell’s DNA.15 These “decorations” confuse the machinery that a cell uses to duplicate its DNA, which impairs the ability of a cell to replicate itself. Thus, cyclophosphamide can significantly impair the function of cells that rely on frequent replication to do their job, like immune cells.

Cyclophosphamide is very good at killing the immune cells that cause inflammation, which makes it a useful treatment for AE. The side effects of cyclophosphamide, however, can include nausea and hair loss, as well as more dangerous conditions such as bladder injuries and problems with fertility.16 Because of this, cyclophosphamide is generally recommended for patients whose symptoms aren’t eliminated by first-line therapies or rituximab.

Symptomatic Treatment of AE

 

The immune-targeting therapies for AE aim at eliminating the source of a patient’s symptoms. But oftentimes it can be beneficial to provide patients with additional therapies that can help alleviate the symptoms themselves. For example, the brain inflammation associated with AE can cause patients to experience seizures.17 Seizures are uncontrolled bursts of electrical activity in the brain. Depending on where a seizure starts and spreads, this electrical activity can result in phenomena ranging from the experience of strange sensations to full-body convulsions.18 Many patients with AE may be prescribed anti-seizures medications, which act to quiet down the electrical activity in the brain and decrease the likelihood of the uncontrolled activity of a seizure.

Medical therapies targeting inflammation dramatically reduce symptoms in the majority of patients diagnosed with AE. Some patients, however, will continue to have symptoms even after treatment, and some may be resistant to treatment altogether. We are still early in our research efforts to try to understand how and why people get AE. And as we deepen our understanding of this complex disorder, hopefully we can work towards developing more treatments specifically targeting the underlying causes of AE that are more effective with fewer side effects.

 

Download PDF Handout

References

  1. Titulaer, M. J. et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. The Lancet Neurology 12, 157–165 (2013).
  2. Abboud, H. et al. Residual symptoms and long-term outcomes after all-cause autoimmune encephalitis in adults. Journal of the Neurological Sciences 434, 120124 (2022).
  3. Dalmau, J. & Rosenfeld, M. R. Paraneoplastic and autoimmune encephalitis.
  4. Lancaster, E. The Diagnosis and Treatment of Autoimmune Encephalitis. J Clin Neurol 12, 1–13 (2016).
  5. Ramamoorthy, S. & Cidlowski, J. A. Corticosteroids-Mechanisms of Action in Health and Disease. Rheum Dis Clin North Am 42, 15–31 (2016).
  6. Hodgens, A. & Sharman, T. Corticosteroids. in StatPearls (StatPearls Publishing, 2022).
  7. Briot, K. & Roux, C. Glucocorticoid-induced osteoporosis. RMD Open 1, e000014 (2015).
  8. Abboud, H. et al. Autoimmune encephalitis: proposed best practice recommendations for diagnosis and acute management. J Neurol Neurosurg Psychiatry 92, 757–768 (2021).
  9. Janeway, C. A., Travers, P., Walport, M. & Shlomchik, M. J. Immunobiology. (Garland Science, 2001).
  10. Bobati, S. S. & Naik, K. R. Therapeutic Plasma Exchange – An Emerging Treatment Modality in Patients with Neurologic and Non-Neurologic Diseases. J Clin Diagn Res 11, EC35–EC37 (2017).
  11. Patient education: Intravenous immune globulin (IVIG) (Beyond the Basics) – UpToDate. https://www.uptodate.com/contents/intravenous-immune-globulin-ivig-beyond-the-basics.
  12. Lee, S. et al. The safety and efficacy of intravenous immunoglobulin in autoimmune encephalitis. Ann Clin Transl Neurol 9, 610–621 (2022).
  13. Hanif, N. & Anwer, F. Rituximab. in StatPearls (StatPearls Publishing, 2022).
  14. Thaler, F. S. et al. Rituximab Treatment and Long-term Outcome of Patients With Autoimmune Encephalitis: Real-world Evidence From the GENERATE Registry. Neurology – Neuroimmunology Neuroinflammation 8, (2021).
  15. Ahlmann, M. & Hempel, G. The effect of cyclophosphamide on the immune system: implications for clinical cancer therapy. Cancer Chemother Pharmacol 78, 661–671 (2016).
  16. Ogino, M. H. & Tadi, P. Cyclophosphamide. in StatPearls (StatPearls Publishing, 2022).
  17. Davis, R. & Dalmau, J. Autoimmunity, Seizures, and Status Epilepticus. Epilepsia 54, 46–49 (2013).
  18. Turek, G. & Skjei, K. Seizure semiology, localization, and the 2017 ILAE seizure classification. Epilepsy & Behavior 126, 108455 (2022).
  19. Feyissa, A. M., López Chiriboga, A. S. & Britton, J. W. Antiepileptic drug therapy in patients with autoimmune epilepsy. Neurol Neuroimmunol Neuroinflamm 4, e353 (2017).

 All figures made with biorender.com.

IAES PNK Partnership logo 500x419 - Treatments for Autoimmune Encephalitis

Click here or the image below to subscribe to our mailing list:

subscribe - Halloween Ideas

Your generous Donations allow IAES to continue our important work and save lives!

 

 

Tabitha Orth 300x218 - Treatments for Autoimmune Encephalitis

 

 

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.

 

guidestar platinum logo 300x300 1 e1605914935941 - Treatments for Autoimmune Encephalitis

 

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.   Trivia Playing cards 3 FB 500x419 - Treatments for Autoimmune Encephalitis 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.   AE Warrior Store 300x200 - Treatments for Autoimmune Encephalitis

Be a part of the solution by supporting IAES with a donation today.

why zebra - Aphasia as a Symptom of Autoimmune Encephalitis
image - Treatments for Autoimmune Encephalitis
Peripheral monocytes and soluble biomarkers in autoimmune encephalitis

Peripheral monocytes and soluble biomarkers in autoimmune encephalitis

by | Mar 29, 2023 | Australian Autoimmune Encephalitis Consortium

March 29, 2023 | Written by Dr. Robb Wesselingh. Edited by Dr Mastura Monif, Dr Loretta Piccenna, Ms Tiffany Rushen, Ms Amanda Wells (consumer representative) Ms Sasha Ermichina (consumer representative), and Ms. Michelle Mykytowycz.

 ——

A message from IAES Blog Staff:

It is our honor and pleasure to present to all of you an overview of Peripheral monocytes and soluble biomarkers in autoimmune encephalitis. This overview is by the esteemed team at Monash University in Australia & lead by Dr. Mastura Monif, who is a member of IAES’ Medical Advisory Board.

We are proud to be in collaboration with Dr. Monif and her team in the Australian Autoimmune Encephalitis Consortium Project as we work closely with them to best support AE patients, caregivers, and their families.

You can find out more about the Australian Autoimmune Encephalitis Consortium and its efforts to help those with AE and their families via the following link:

https://www.monash.edu/medicine/autoimmune-encephalitis

 —-—-

Peripheral monocytes and soluble biomarkers in autoimmune encephalitis

Source: R Wesselingh, S Griffith, J Broadley, D Tarlinton, K Buzzard, U Seneviratne, H Butzkueven, TJ O’Brien, M Monif, Peripheral monocytes and soluble biomarkers in autoimmune encephalitis, Journal of Autoimmunity, 2023; 135 https://doi.org/10.1016/j.jaut.2023.103000

Introduction

Autoimmune encephalitis (AE) is a condition in which inflammation occurs in various regions of the brain. In AE a person’s immune system produces antibodies (proteins) that mistakenly targets components of the person’s own neurons (nerve structures). This can result in inflammation and nerve tissue damage. As a result, a person with AE can present with different neurological symptoms including seizures (sudden, uncontrolled electrical disturbances in the brain) and memory problems. There are different types of AE based on which protein the immune system is mistakenly targeting. Two of the most common types of AE are:

  • NMDAR AE – antibodies targeting a brain protein called N-methyl-D-aspartate receptor or NMDAR and
  • LGI-1 AE – antibodies targeting a brain protein called leucine-rich, glioma inactivated-1 or LGI-1

While we know antibodies play a key role in the disease, we do not know what changes occur in other parts of the immune system during the course of AE.

The innate immune system is a part of the immune system that acts as a broad first line of defence against foreign invaders to the body like viruses and bacteria. This system can often start or increase inflammation in the body as a protective mechanism. Monocytes are a major type of cell in the innate immune system that drive this response. Monocytes can alert and activate other parts of the immune system through release of small signalling proteins. These small signalling proteins can be released into the blood and tissues and are called cytokines. In AE it is unknown whether the innate immune system or monocytes play a role in the disease.

For this research, we set out to find out answers to following –

  1. Are monocytes in people with AE different than in healthy people?
  2. Is there other evidence of inflammation in the blood of people with AE?
  3. Does the level of inflammation in AE determine disease severity?
  4. Are the inflammatory changes the same in different types of AE?

How we did this work

We recruited 40 people with AE and 28 healthy volunteers who provided blood samples. These blood samples were evaluated in the laboratory for:

  • Characteristics of the monocytes (whether they show signs of being active and more inflammatory), and
  • Levels of different cytokines in the blood that may show increased activity of the immune system and increased inflammation

These findings were then compared between people with AE and the healthy volunteers to see if there were any differences. We also compared these findings between people with different types and severities of AE.

What were the interesting things we found

  • We found that a certain type of monocyte known to play a key role in inflammation in other diseases are increased in number in people with AE compared with healthy volunteers
  • We also identified that certain cytokines (IL-6, TNF-a) that are important in starting and maintaining inflammation are also increased in people with AE compared with healthy volunteers
  • These changes were present in both severe and mild AE but were much stronger in people with LGI-1 antibody associated AE.

What do these findings mean?

This research showed that there is ongoing inflammation in the blood of people with AE. Also, monocytes and the innate immune system may play a role in the disease.

The research could help clinicians to –

  1. Identify new treatments that target monocytes and the innate immune system
  2. Use the inflammatory changes identified as a way to diagnose and monitor the disease.

———-

For more information and resources from Dr. Monif and her group at the Australian Autoimmune Encephalitis Consortium Project, visit this link here. To download a plain language PDF of the paper summarized in this blog, click the button below:

Download Plain Language Summary

 

Click here or the image below to subscribe to our mailing list:

subscribe - Halloween Ideas

Your generous Donations allow IAES to continue our important work and save lives!

 

Tabitha Orth 300x218 - Peripheral monocytes and soluble biomarkers in autoimmune encephalitis

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.

guidestar platinum logo 300x300 1 e1605914935941 - Peripheral monocytes and soluble biomarkers in autoimmune encephalitis

 

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.   Trivia Playing cards 3 FB 500x419 - Peripheral monocytes and soluble biomarkers in autoimmune encephalitis 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.   AE Warrior Store 300x200 - Peripheral monocytes and soluble biomarkers in autoimmune encephalitis

Be a part of the solution by supporting IAES with a donation today.

why zebra - Aphasia as a Symptom of Autoimmune Encephalitis
What is a headache?

What is a headache?

by | Mar 7, 2023 | PennNeuroKnow


March 8, 2023 | by Marissa Maroni, 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/

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:

  1. 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.

  1. 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.

  1. 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.

headache 2 496x500 - What is a headache?

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.

migraine pain 500x177 - What is a headache?

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

  1. 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.
  2. 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.
  3. Dodick, D. W. (2018). A phase‐by‐phase review of migraine pathophysiology. Headache: the journal of head and face pain, 58, 4-16.
  4. Pescador Ruschel MA, De Jesus O. Migraine Headache. 2022 Jul 6. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan–. PMID: 32809622.
  5. 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.
  6. Puledda, F., Messina, R., & Goadsby, P. J. (2017). An update on migraine: current understanding and future directions. Journal of neurology, 264(9), 2031-2039.
  7. Stankewitz, A., Aderjan, D., Eippert, F., & May, A. (2011). Trigeminal nociceptive transmission in migraineurs predicts migraine attacks. Journal of Neuroscience, 31(6), 1937-1943.
  8. 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.
  9. Karsan, N., & Goadsby, P. J. (2018). Biological insights from the premonitory symptoms of migraine. Nature Reviews Neurology, 14(12), 699-710.
  10. Pietrobon, D., & Moskowitz, M. A. (2013). Pathophysiology of migraine. Annual review of physiology, 75, 365-391.
  11. Burstein, R., Noseda, R., & Borsook, D. (2015). Migraine: multiple processes, complex pathophysiology. Journal of Neuroscience, 35(17), 6619-6629.
  12. Russo, A. F. (2015). Calcitonin gene-related peptide (CGRP): a new target for migraine. Annual review of pharmacology and toxicology, 55, 533.
  13. 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.
  14. 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).
  15. Johnston, M. M., & Rapoport, A. M. (2010). Triptans for the management of migraine. Drugs, 70(12), 1505-1518.

Cover photo by Robin Higgins from Pixabay

Figures created with BioRender.com.

 

 

 

IAES PNK Partnership logo 500x419 - What is a headache?

Click here or the image below to subscribe to our mailing list:

subscribe - Halloween Ideas

Your generous Donations allow IAES to continue our important work and save lives!

 

 

Tabitha Orth 300x218 - What is a headache?

 

 

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.

 

guidestar platinum logo 300x300 1 e1605914935941 - What is a headache?

 

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.   Trivia Playing cards 3 FB 500x419 - What is a headache? 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.   AE Warrior Store 300x200 - What is a headache?

Be a part of the solution by supporting IAES with a donation today.

why zebra - Aphasia as a Symptom of Autoimmune Encephalitis
image - What is a headache?
Why does it feel like we know so little about autoimmune encephalitis?

Why does it feel like we know so little about autoimmune encephalitis?

by | Feb 21, 2023 | PennNeuroKnow

February 22, 2023 | by Catrina 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).

1583 map - Why does it feel like we know so little about autoimmune encephalitis?

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.

Autoimmune encephalitis is a good example of this kind of complexity. There are many different subtypes of autoimmune encephalitis that result from an immune response to several different kinds of proteins found in the brain. Despite being caused by reactions to different proteins, several subtypes have overlapping symptoms. On the other hand, each subtype is typically associated with several distinct symptoms that are all part of the same diagnosis. On top of that, each individual patient is different even before they get sick, so they will have a slightly different experience of their disease.

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.

Image Credits

Cover photo: Photo by Ousa Chea on Unsplash.

Figure 1: Left: Girolamo Porro,, Public domain, via Wikimedia Commons; Right: © OpenStreetMap-Mitwirkende, Public domain, via Wikimedia Commons

 

 

 

IAES PNK Partnership logo 500x419 - Why does it feel like we know so little about autoimmune encephalitis?

Click here or the image below to subscribe to our mailing list:

subscribe - Halloween Ideas

Your generous Donations allow IAES to continue our important work and save lives!

 

 

Tabitha Orth 300x218 - Why does it feel like we know so little about autoimmune encephalitis?

 

 

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.

 

guidestar platinum logo 300x300 1 e1605914935941 - Why does it feel like we know so little about autoimmune encephalitis?

 

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.   Trivia Playing cards 3 FB 500x419 - Why does it feel like we know so little about autoimmune encephalitis? 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.   AE Warrior Store 300x200 - Why does it feel like we know so little about autoimmune encephalitis?

Be a part of the solution by supporting IAES with a donation today.

why zebra - Aphasia as a Symptom of Autoimmune Encephalitis
image - Why does it feel like we know so little about autoimmune encephalitis?
Peripheral monocytes and soluble biomarkers in autoimmune encephalitis

Psychiatric Manifestations of Autoimmune Encephalitis

by | Jan 24, 2023 | Australian Autoimmune Encephalitis Consortium


January 25, 2023 | Written by Dr. Hannah Ford. Edited by Dr Mastura Monif, Dr Loretta Piccenna, Ms Sarah Griffith, Ms Tiffany Rushen, Ms Amanda Wells (consumer representative) and Ms Sasha Ermichina (consumer representative).

image - Psychiatric Manifestations of Autoimmune Encephalitis

A message from IAES Blog Staff:

It is our honor and pleasure to present to all of you an overview of typical psychiatric manifestations of autoimmune encephalitis This overview is by the esteemed team at Monash University in Australia & lead by Dr. Mastura Monif, who is a member of IAES’ Medical Advisory Board.

We are proud to be in collaboration with Dr. Monif and her team in the Australian Autoimmune Encephalitis Consortium Project as we work closely with them to best support AE patients, caregivers, and their families.

You can find out more about the Australian Autoimmune Encephalitis Consortium and its efforts to help those with AE and their families via the following link:

https://www.monash.edu/medicine/autoimmune-encephalitis

 —-

Psychiatric Manifestations of Autoimmune Encephalitis

WHY WE DID THIS WORK

Autoimmune encephalitis is a disorder in which antibodies accidentally created by the immune system attack parts of the brain. This can lead to inflammation and nerve damage.

Psychiatric problems are common in autoimmune encephalitis and can imitate mental health conditions, for example psychotic illnesses like schizophrenia. It is important to separate patients with AE from those with mental illness as treatments are very different.

There are different subtypes of AE. Some cases are due to the presence of detectable auto antibodies (a protein targeting the person’s own nerve endings) which is known as ‘sero positive’ AE. In ‘sero negative’ AE, there is no detectable antibody when using currently available techniques for detection.

Within the ‘sero positive’ group are different AE categories depending on the type of antibody. We discuss this further in the next section.

Anti-NMDAR encephalitis

  • The most common type of AE and typically occurs in young women. Psychiatric problems are the presenting feature in most patients and many are seen first by a psychiatrist. Symptoms start abruptly and progress rapidly over days to weeks.
  • Common features include psychosis (disruption of person’s thoughts and perceptions that can make it difficult for them to understand what is real versus what is not real). They can present with hallucinations (seeing or hearing things that are not there) and paranoia (false beliefs; for example, believing that people are out there to get you, or having unfounded mistrust of others), agitation, and elevated mood. Occasionally, anti NMDAR encephalitis patients can present with catatonia (complete lack of movement or lack of communication). Almost 90% of patients develop other related neurologic features (including seizures, abnormal movements and speech, and drowsiness) within a month, however some may have only psychiatric problems without neurologic signs.

Anti-LGI1 encephalitis

  • The second most common AE and typically affects older males. Seizures are usually the first symptom and often occur before patients develop psychiatric and/or memory problems. These seizures can be very brief, i.e. seconds long, and subtle (face and arm twitching known as “faciobrachial dystonic seizures”), but can be very frequent (up to 100s of times per day).
  • Memory difficulties develop slowly over months and may be accompanied by disinhibition (actions or words that might seem inappropriate or rude or inconsiderate).
  • They can also present with compulsive behaviors (performing an action persistently repetitively), including excessive eating, cleaning and hoarding.
  • Psychotic symptoms such as hallucinations and paranoia can occur but are less common, and usually are not an early or major feature.

Anti-CASPR encephalitis

  • Involves confusion, memory difficulties and ‘slow’ thinking which may be associated with depressed mood. Memory problems can slowly worsen over 12 months or longer in a proportion of patients. These individuals may appear like they have dementia.
  • Psychotic symptoms such as hallucinations, delusions and paranoia can occur as inflammation of the brain worsens, and usually develop with other neurologic symptoms including seizures, unsteadiness and abnormal jerking and twitching movements.

Anti-AMPAR encephalitis

  • Typically presents with short-term memory problems, confusion and behavioral changes which get worse over weeks to months.
  • Psychotic symptoms are variable (20-90% of patients) and may be associated with manic (abnormally elevated or extreme in mood, emotions, energy or activity levels) and aggressive behavior.
  • Seizures are rare. This type of encephalitis is frequently associated with cancer.

Anti-GABA-A encephalitis

  • Most commonly presents with seizures.
  • Memory loss and confusion develop slowly over weeks to months and are associated with personality and behavioral changes in approximately half of patients.
  • Features of psychosis with hallucinations and paranoia are uncommon but can occur later in severe cases.

Anti-GABA-B encephalitis

  • Also commonly presents with seizures.
  • Memory difficulties, confusion and abnormal behavior develop with or after seizures start.
  • Patients often become depressed and/or anxious at a later stage, usually 1 to 2 years after other symptoms have started.
  • Memory difficulties are slow to improve and may remain even after treatment.
  • Psychosis is not a feature.

Anti-DPPX encephalitis

  • Preceded by diarrhea and weight loss for several months, followed by mild, slowly worsening memory and cognitive difficulties associated with depression and anxiety.
  • Months or even years later patients develop psychotic features including hallucinations, delusions and aggression with neurologic symptoms such as seizures, limb shaking and jerking.

Anti-mGluR5 encephalitis

  • A rare type of AE with three major features – psychosis, memory problems and drowsiness.
  • Patients experience headaches, fevers, weight loss and nausea followed by rapid onset of memory problems, slowed thinking and severe psychiatric symptoms including hallucinations, depression, anxiety and major mood swings.
  • Many different neurologic symptoms can occur, including seizures, abnormal movements and difficulty using the eyes and face.

Anti-Neurexin-3a encephalitis

  • The disorder develops quickly over several days with headaches, fevers and nausea, followed by confusion and agitation.
  • Patients then experience severe neurologic symptoms of drowsiness, abnormal movements, seizures and breathing problems.

Diagnosis and treatment

  • Features (“red flags”) that may indicate AE as a cause of psychiatric presentation are shown in table 1.
  • Diagnosis of AE is challenging, and is confirmed by identifying the antibody in the blood or fluid from around the brain and spinal cord (cerebrospinal fluid), however these tests are not always available and may take a long time to return. Other test results that indicate AE may be the cause of psychiatric symptoms include high white cells or inflammation in cerebrospinal fluid, abnormal brain imaging on MRI and abnormal brain electrical activity on EEG (electroencephalogram; refer to our previous summary on EEG here: https://autoimmune-encephalitis.org/using-eeg-nmda
  • Early treatment of AE can lead to partial or full recovery.

Table 1.

Red Flags for Autoimmune Encephalitis in Psychiatric Presentations

·       Preceding physical symptoms such as fever, headache, stomach upset and dizziness

·       Seizures

·       Neurologic symptoms such as abnormal movements, speech difficulties, clumsiness, weakness and changes in sensation

·       “Catatonic” features such as abnormal posturing, repeating another person’s speech (echolalia), lack of movement or erratic movements

·       Memory problems

·       Psychotic symptoms that start rapidly and/or worsen quickly

 

What do the findings mean?

  • Each subtype of AE presents with different psychiatric features. Our research can help clinicians identify patients with psychiatric symptoms due to AE rather than a mental illness.
  • Early consideration of AE as a differential for psychiatric presentations is important as patients respond well to appropriate treatment (immunotherapy), particularly if given early.
  • Further studies are needed to continue describing the syndromes associated with each subtype. Fast and accurate testing for the diagnosis of AE is an important area for future research.

—-

For more information and resources from Dr. Monif and her group at the Australian Autoimmune Encephalitis Consortium Project, visit this link here. To download a plain language PDF of the paper summarized in this blog, click the button below:

Download Plain Language Summary

 

Click here or the image below to subscribe to our mailing list:

subscribe - Halloween Ideas

Your generous Donations allow IAES to continue our important work and save lives!

 

Tabitha Orth 300x218 - Psychiatric Manifestations of Autoimmune Encephalitis

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.

guidestar platinum logo 300x300 1 e1605914935941 - Psychiatric Manifestations of Autoimmune Encephalitis

 

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.   Trivia Playing cards 3 FB 500x419 - Psychiatric Manifestations of Autoimmune Encephalitis 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.   AE Warrior Store 300x200 - Psychiatric Manifestations of Autoimmune Encephalitis

Be a part of the solution by supporting IAES with a donation today.

why zebra - Aphasia as a Symptom of Autoimmune Encephalitis
What are the different types of autoimmune encephalitis?

What are the different types of autoimmune encephalitis?

by | Dec 27, 2022 | PennNeuroKnow

December 28, 2022 | by Sophie Liebergall, 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/

——

Introduction

Receiving a diagnosis of autoimmune encephalitis can be a stressful and uncertain time for many patients and their families. And to make it even more confusing, doctors often don’t just give patients a diagnosis of autoimmune encephalitis, but rather anti-NMDAR or anti-Hu or anti-GABAA encephalitis. There are many different types and subtypes of autoimmune encephalitis that can have distinct symptoms, underlying causes, and responses to treatment.1However, the terminology that doctors use to refer to these different subtypes is complex and can sometimes feel like wading into a bowl of alphabet soup! Here, we will try to break down some of the ways that doctors distinguish types of autoimmune encephalitis to help patients and their families make sense of this complicated and rapidly evolving field.

What is autoimmune encephalitis?

Before we break down the different types of autoimmune encephalitis, it is important to understand what autoimmune encephalitis is. What do doctors mean when they use the term autoimmune encephalitis? The suffix -itis can be applied to any part of the body to describe an inflammatory state. So, when -itis is added to the end of the word encephalon (which is the ancient Greek word for inside the head), it means inflammation of the brain. Therefore, encephalitis is a word that describes any sort of inflammation in the brain.

But what exactly is inflammation? What does it mean when a part of the body is inflamed? Inflammation occurs when the body’s immune system is activated.2 Typically, the immune system is activated when there are invaders in the body, such as bacteria or viruses. Once the immune system is alerted to the presence of this invader, it tries to eliminate the invader using a variety of different weapons. Some of the weapons that the immune system uses are called antibodies.3Antibodies act as signals for the immune system so that it knows where to direct its attack. One battalion of the immune system’s cell soldiers makes antibodies that specifically stick to the target. Then, the immune system sends another battalion of cell soldiers to eliminate the target that has been flagged by the antibody.

Even though the immune system’s main job is to mount attacks against invaders like bacteria and viruses, things can go wrong in the fog of biological warfare. Sometimes the immune system accidentally mounts an attack against healthy proteins in a person’s body. When the body’s immune system targets itself, it can result in what is called an autoimmune process (from combining auto-, meaning self, and -immune, as in the immune system).

Now we can put all of these terms together! When the body’s immune system accidentally targets healthy proteins in a person’s brain, resulting in inflammation in the brain, it is called autoimmune encephalitis.4

It is important to note that when the body mounts an autoimmune attack against the brain, it isn’t trying to target everyhealthy protein in the brain. Rather, it’s generally trying to target specific proteins that are found in the brain. When the immune system attacks these proteins, it can damage the proteins and the cells in which they are found. As a result, the type of autoimmune encephalitis and the symptoms associated with that autoimmune encephalitis are based on the type of protein that is targeted for attack by the immune system.5

What part of the brain is affected by autoimmune encephalitis?

Though we are still relatively early in our understanding of how the brain works, we do know that different regions of the brain control different brain functions. For example, some areas of the brain are dedicated to controlling movement, whereas others are dedicated to processing sensory stimuli. One way in which these different regions of the brain are distinct is that their brain cells can contain different proteins. This means that when the immune system mounts an attack against a protein in the brain, this attack is targeted to the regions in the brain where that protein is found. Therefore, the distinct types of autoimmune encephalitis target different regions in the brain and may affect different brain functions.1

Doctors will sometimes describe a patient’s encephalitis based on which part of the brain they suspect is being attacked. Some common terms that you may hear a doctor use to describe autoimmune encephalitis include:

  • Limbic encephalitis: inflammation of the limbic system. The limbic system includes brain regions such as the hippocampus, amygdala, and hypothalamus that are involved in emotional regulation. People with limbic encephalitis most commonly have changes in their mood and memory, along with seizures starting in the limbic system.6
  • Brainstem encephalitis: inflammation of the brainstem which is the long stalk at the base of the brain that connects the brain to the spinal cord. The brainstem is the center of many important functions necessary for survival, so people with brainstem encephalitis can have problems ranging from abnormal eye movements to trouble swallowing or breathing.7
  • Encephalomyelitis: inflammation of the brain plus inflammation of the spinal cord. Sometimes patients with autoimmune encephalitis can also mount an autoimmune attack on their spinal cord. Inflammation in the spinal cord interferes with the sensory and movement signals that are sent between the brain and the rest of the body, which can result in symptoms like weakness, paralysis, numbness, or tingling.8

Is autoimmune encephalitis caused by a tumor?

Another way that doctors distinguish between the types of autoimmune encephalitis is by using the terms paraneoplastic vs. non-paraneoplastic encephalitis. In paraneoplastic autoimmune encephalitides, the reason that the patient’s immune system is attacking their brain is because they have a tumor somewhere in their body.13 A tumor, which is a growth of abnormal cells, can be one of the most common causes of autoimmune encephalitis. This is because the abnormal cells in a tumor can sometimes do strange things to proteins normally found in the brain. For example, tumor cells can place a protein that is normally supposed to be inside of the cell on the outside of the cell, or they can begin to make a brain protein in a different part of the body where it is not normally supposed to be made. This can confuse the immune system, which causes it to attack a normal brain protein that it would otherwise leave alone.9

In contrast to these cases of paraneoplastic encephalitis, non-paraneoplastic autoimmune encephalitis occurs when there is an autoimmune encephalitis but doctors can’t find a tumor anywhere in the person’s body.1 In these cases, what is causing the immune system to all of a sudden decide to attack a healthy protein in the brain is less clear. The cause of cases of non-paraneoplastic autoimmune encephalitis is the subject of ongoing and future research by many doctors and scientists.

Which protein in the brain is the immune system trying to attack?

Perhaps the most specific way in which doctors can distinguish between different types of autoimmune encephalitis is by determining exactly which protein in the brain is being targeted. As discussed above, when the immune system mounts an attack against its target, it makes antibodies to specifically flag this target. These antibodies circulate in the blood and/or the fluid that bathes the brain. Therefore, if doctors can collect these antibodies, they can provide a clue about which protein the immune system is targeting.

As doctors and scientists have identified more antibodies involved in autoimmune encephalitis, they have started to name these types of autoimmune encephalitis after the antibody that is present. For example, one of the most common forms of autoimmune encephalitis is caused by the body mounting an attack against the NMDA receptor, which is a protein found on the surface of many cells in the brain.10 These antibodies against the NMDA receptor are called “anti-NMDA receptor antibodies” so these patients are said to have “anti-NMDA receptor autoimmune encephalitis.” Some of the most common types of autoimmune encephalitis that are named based on the antibody found against their protein target are listed in the table below.

Antibody

% of Cases with Presence of Tumor

Common symptoms

Anti-NMDAR

40% (varies)

Limbic encephalitis, psychosis, repetitive movements, unstable blood pressure and heart rate, decreased breathing, seizures

Anti-AMPAR

70%

Limbic encephalitis

Anti-GABAA

 

Severe, prolonged seizures

Anti-GABAB

70%

Limbic encephalitis, frequent seizures

Anti-Caspr2

40%

Limbic encephalitis, confusion, abnormal muscle tone

Anti-LGI1

<10%

Limbic encephalitis, seizures

Anti-Hu

>90%

Limbic encephalitis, problems with cognition

Anti-Ma2

>90%

Limbic encephalitis, brainstem encephalitis

Anti-CV2/CRMP5

>90%

Limbic encephalitis

Anti-Amphiphysin

>90%

Limbic encephalitis, widespread paralysis

 

Table Caption: Different antibodies that are found in patients with autoimmune encephalitis are associated with distinct symptoms and the likelihood that the disease is a result of having a tumor somehwere in the body. Adapted from Davis & Dalmau – Autoimmunity, seizures & status epilepticus (2013).11

In some patients doctors are unable to find an antibody that is known to be associated with autoimmune encephalitis, even if the doctor is pretty sure that the patient’s symptoms are caused by an autoimmune encephalitis. This might be because either the patient’s immune system is not making an antibody, or that doctors don’t yet have a laboratory test that is capable of identifying an antibody associated with that patient’s disease. These cases of autoimmune encephalitis are said to be seronegative.12 Doctors and scientists are still looking to identify new proteins and antibodies that are associated with autoimmune encephalitis in hopes of providing a more specific diagnosis for patients who would have previously been thought to have seronegative autoimmune encephalitis.

It is important to remember that autoimmune encephalitis can look different in every patient. For example, one patient may be diagnosed with anti-NMDA encephalitis after she has multiple seizures and is found to have an ovarian tumor. Whereas another patient may be diagnosed with anti-NMDA encephalitis after he has dramatic changes in his personality and memory, but doctors are not able to find a tumor. Nevertheless, breaking down a disease into distinct boxes can help guide doctors in their diagnostic and treatment decisions for an individual patient. And a greater understanding of the subtypes and causes of autoimmune encephalitis may be crucial for developing more targeted and effective treatments for this uniquely challenging disease.

References:

  1. Dalmau, J. & Rosenfeld, M. R. Paraneoplastic and autoimmune encephalitis.
  2. Chen, L. et al. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget 9, 7204–7218 (2017).
  3. Janeway, C. A., Travers, P., Walport, M. & Shlomchik, M. J. Immunobiology. (Garland Science, 2001).
  4. Abboud, H. et al. Autoimmune encephalitis: proposed best practice recommendations for diagnosis and acute management. J Neurol Neurosurg Psychiatry 92, 757–768 (2021).
  5. Lancaster, E. The Diagnosis and Treatment of Autoimmune Encephalitis. J Clin Neurol 12, 1–13 (2016).
  6. Gultekin, S. H. et al. Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumour association in 50 patients. Brain 123 ( Pt 7), 1481–1494 (2000).
  7. Tan, I. L. et al. Brainstem encephalitis: etiologies, treatment, and predictors of outcome. J Neurol 260, 2312–2319 (2013).
  8. Dalmau, J., Graus, F., Rosenblum, M. K. & Posner, J. B. Anti-Hu–associated paraneoplastic encephalomyelitis/sensory neuronopathy. A clinical study of 71 patients. Medicine (Baltimore) 71, 59–72 (1992).
  9. Dalmau, J. & Graus, F. Antibody-Mediated Encephalitis. N Engl J Med 378, 840–851 (2018).
  10. Barry, H., Byrne, S., Barrett, E., Murphy, K. C. & Cotter, D. R. Anti-N-methyl-d-aspartate receptor encephalitis: review of clinical presentation, diagnosis and treatment. BJPsych Bull 39, 19–23 (2015).
  11. Davis, R. & Dalmau, J. Autoimmunity, Seizures, and Status Epilepticus. Epilepsia 54, 46–49 (2013).
  12. Lee, W. J. et al. Seronegative autoimmune encephalitis: clinical characteristics and factors associated with outcomes. Brain awac166 (2022) doi:10.1093/brain/awac166.
  13. Rees, J H. “Paraneoplastic Syndromes: When to Suspect, How to Confirm, and How to Manage.” Journal of Neurology, Neurosurgery & Psychiatry 75, (June 1, 2004): ii43–50. https://doi.org/10.1136/jnnp.2004.040378.

 

 

IAES PNK Partnership logo 500x419 - What are the different types of autoimmune encephalitis?

Click here or the image below to subscribe to our mailing list:

subscribe - Halloween Ideas

Your generous Donations allow IAES to continue our important work and save lives!

 

 

Tabitha Orth 300x218 - What are the different types of autoimmune encephalitis?

 

 

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.

 

guidestar platinum logo 300x300 1 e1605914935941 - What are the different types of autoimmune encephalitis?

 

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.   Trivia Playing cards 3 FB 500x419 - What are the different types of autoimmune encephalitis? 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.   AE Warrior Store 300x200 - What are the different types of autoimmune encephalitis?

Be a part of the solution by supporting IAES with a donation today.

why zebra - Aphasia as a Symptom of Autoimmune Encephalitis
image - What are the different types of autoimmune encephalitis?
My letter to Santa ATTENTION: YULETIDE BUREAU WISH DEPARTMENT

My letter to Santa ATTENTION: YULETIDE BUREAU WISH DEPARTMENT

by | Dec 24, 2022 | Holiday Stories

 

December 24, 2022 | Tabitha Andrews Orth 

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 

Tabithas letter to Santa facebook Post 300x251 - My letter to Santa ATTENTION: YULETIDE BUREAU WISH DEPARTMENT

(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!

Click here or the image below to subscribe to our mailing list:

subscribe - Halloween Ideas

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.

guidestar platinum logo 300x300 1 e1605914935941 - My letter to Santa ATTENTION: YULETIDE BUREAU WISH DEPARTMENT

 

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

Submit Your Story

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.

Trivia Playing cards 3 FB 500x419 - The Real-World Challenges of Surviving an Autoimmune Encephalitis Diagnosis

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.

AE Warrior Store 300x200 - The Real-World Challenges of Surviving an Autoimmune Encephalitis Diagnosis

why zebra - My letter to Santa ATTENTION: YULETIDE BUREAU WISH DEPARTMENT
How does the brain heal from autoimmune encephalitis and why is there so much variability in the healing process?

How does the brain heal from autoimmune encephalitis and why is there so much variability in the healing process?

by | Dec 6, 2022 | PennNeuroKnow

December 7, 2022 | by Kara McGaughey, PennNeuroKnow

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/

——

The holy grail! The million-dollar question! How long will it take to get rid of AE, to heal from AE…when will we feel and act ‘normal’ again? Why do we not understand more of the healing process’ from a diagnosis of autoimmune encephalitis?

Kara McGaughey and the team at PennNeuroKnow help us further understand just how complex and individual our brains are!

——

Introduction

 

If you break a bone, your expectations about the healing process and how long it might last will vary depending on the nature and severity of the fracture. For example, a small fracture will come with a completely different timeline for recovery than a compound fracture (where the force of the break causes the bone to pierce through the skin).

Just like broken bones, no two cases of brain injury are exactly the same and the timeline of the healing process depends on the nature and severity of the injury. As such, when we consider healing from brain injuries, like autoimmune encephalitis (AE), the diversity of diagnoses and symptoms leads to a diversity of recovery trajectories, which can make navigating the healing process a confusing and isolating experience. Here, we dive into this diversity, exploring what healing from AE looks like, why the process takes so long, and why it varies so much.

How does the brain heal from autoimmune encephalitis?

 

“I felt like a robot controlling my body for the first time – speech, thought and movement all under shaky manual control. I felt like my brain was being reacquainted with my body.”

— Alexandrine Lawrie on AE recovery1

Autoimmune encephalitis (AE) is a collection of related conditions in which the body’s immune system produces antibodies that mistakenly attack the brain, causing inflammation. In order to begin the healing process, treatment is needed to shut down the overactive immune system, remove the antibodies mounting the attack, and reduce brain swelling.2-3 To accomplish this, doctors typically rely on a handful of treatments options:

  • Corticosteroids to reduce brain inflammation/swelling and immune system activity.
  • Blood plasma exchange to remove and replace the harmful antibodies circulating in the blood (which can find their way into the brain).
  • Intravenous immunoglobulin (IVIG), which includes helpful antibodies isolated from the blood plasma of thousands of healthy donors.
  • Immunosuppressant medications (like Cyclophosphamide and Rituximab) to directly suppress the immune system, if necessary.2-4

Steroids, blood plasma exchange, intravenous immunoglobulin, or a combination of the three represent the most common defense against AE.2,4 These first-line treatments can be helpful for stopping the immune system’s attack on brain tissue and reducing inflammation. Corticosteroids, for example, reduce brain swelling by preventing the production of inflammatory proteins by immune cells. These steroids also help to restore the integrity of the blood-brain barrier, a protective lining that shields the brain from inflammatory cells and  harmful antibodies that may be circulating in the bloodstream.5 In AE the blood-brain barrier can spring leaks, which allows antibodies from the bloodstream to penetrate the brain and wreak havoc.6 Closing up any leaks in the barrier that formed as a result of AE disease progression is a critical first step in the healing process.

However, recovery from AE can take time and is often not an abrupt rise and fall of symptoms (Figure 1, left). Instead, while many people do respond to available treatment options, the initial period of healing usually falls short of complete, giving way to a longer and more complicated recovery trajectory (Figure 1, center). For example, first-line therapies fail to resolve symptoms in about 50% of patients with AE, which means that additional and prolonged treatments are often required to suppress the immune system and give the brain an opportunity to repair and recover.4 In these cases, doctors turn to second-line therapies, like immunosuppressants. While having steroids on board promotes brain healing by stopping the leakage of antibodies from the bloodstream into the brain, immunosuppressants, like Rituximab, go after the cells that make the antibodies in the first place.5 When given long-term, Rituximab can be effective at reducing symptoms and keeping AE in remission.2,4

pnk symptoms - How does the brain heal from autoimmune encephalitis and why is there so much variability in the healing process?

Figure 1: Rather than a simple rise in symptoms that is quickly attenuated with treatment (black line, left), the timeline of healing from AE often comes with a series of ups and downs (green line, center). The height of these highs and lows depends on many factors, such as the specific AE diagnosis (i.e., the type of antibody causing the attack and the brain areas involved) and the time between symptom onset and treatment. As such, each AE patient’s path to recovery looks different (right).

While therapies, like Rituximab, can be incredibly effective, outcomes are still highly variable. Because no two cases of AE are exactly the same, no two recovery trajectories are either (Figure 1, right). Both treatment options and outcomes often depend on details of the AE diagnosis, such as the type of antibody involved. For example, a recent study of 358 patients with AE demonstrated that people with anti-NMDAR antibodies, LGI1 antibodies, and CASPR2 antibodies respond differently to Rituximab immunotherapy.7 These groups of patients with AE caused by different antibodies not only reported differences in symptom relief, but they ultimately reached different levels of day-to-day independence. Nevertheless, regardless of treatment approach and AE diagnosis, early and aggressive therapy is consistently associated with better outcomes. This means that as diagnostic tools and treatments improve, more people with AE have the opportunity to heal.2

How long does the process of healing from autoimmune encephalitis take?

“Good, bad, up, down, round and round;

I feel as though I’m on a merry-go-round.

Full of uncertainty if it will ever stop spinning;

Full of frustration as I remain on my couch sitting.

It’s going to be alright; it’s going to be okay; I will continue the fight day to day.

I will keep the hope and learn to cope;

I will continue my way up this slippery slope with hopes of support and love of some sort.”

— Anonymous on living with AE8

Since people tend to differ in their response to AE treatments, they tend to recover at different paces. For some, AE symptoms decline steadily with continued immunotherapy, leading to recovery within a couple months. Others experience persistent relapses, leading to a recovery timeline on the order of years (Figure 1, right). Research studies show that most patients continue to improve 18 months to 2 years after starting treatment, but there are some people with AE who experience ongoing and life-changing symptoms.9

Similar to how some types of AE respond better or worse to particular treatments, AE diagnosis also affects the timeline of recovery and the risk of recurrence. A recent study followed up with AE patients 3, 6, and 12 months after starting treatment, assessing and comparing their symptoms using a measure of the degree of disability or dependence. Researchers and clinicians found that after three months, two thirds of patients with anti-LGI1 or CASPR2 antibodies recovered to “slight disability” compared to only 30% of patients with anti-NMDAR or other antibody-based AE.10

This persistence of symptoms among patients with anti-NMDAR vs. anti-LGI1 or CASPR2 AE may come from the fact that different AE antibodies carry different risks for relapse. For example, the risk of relapse within two years for anti-NMDAR AE is 12%.9 There are other AE diagnoses, like anti-AMPAR AE, where the relapse rate is even higher, pushing 50-60%.11 This increased risk of relapse is thought to stem from the fact that patients with anti-AMPAR AE often have psychiatric and memory dysfunction that make them less likely to keep up with medications. However, while it may be more prevalent for some types of AE than others, relapse is not a given. These same studies show that patients who receive (and continue) with first-line treatments have a lower risk of recurrence relative to untreated patients.11 Risk of relapse is further decreased in patients who have been given both first- and second-line therapies.5,9 This clear payoff of continued treatment suggests that as we continue to make improvements to AE therapies, there is potential for the percentage of patients reaching recovery to continue to increase.

All in all, vast differences in AE diagnoses and symptoms lead to lots of variability in treatment options, the healing process, and recovery timelines. This diversity of AE trajectories makes setting expectations for the healing process especially difficult. It also highlights the resilience of AE patients, their families, and their support systems who tirelessly endure and advocate despite prolonged uncertainty.

“A dear lady friend of mine (with the same illness) said this great quote that I reflect on frequently:

‘Not every day is good, but there is good in every day.’

And that has been absolutely true.

Each day presents itself with its own challenges and even though I don’t know what the future holds,

I am most calm when I focus on the good one day at a time.

–Amy on her AE journey12

Work Cited:

  1. Lawrie, A. My experience with autoimmune encephalitis: A year of recovery. The Health Policy Partnership (2022). Available at: https://www.healthpolicypartnership.com/my-experience-with-autoimmune-encephalitis-a-year-of-recovery/. (Accessed: 25th October 2022).
  2. Dinoto, A., Ferrari, S. & Mariotto, S. Treatment options in refractory autoimmune encephalitis. CNS Drugs 36, 919–931 (2022).
  3. Abboud, H. et al. Autoimmune encephalitis: Proposed best practice recommendations for diagnosis and Acute Management.Journal of Neurology, Neurosurgery, and Psychiatry 92, 757–768 (2021).
  4. Dalmau, J. & Rosenfeld, M. R. Autoimmune encephalitis update. Neuro-Oncology 16, 771–778 (2014).
  5. Shin, Y.-W. et al. Treatment strategies for autoimmune encephalitis. Therapeutic Advances in Neurological Disorders 11, 1–19 (2018).
  6. Platt, M. P., Agalliu, D. & Cutforth, T. Hello from the other side: How autoantibodies circumvent the blood–brain barrier in autoimmune encephalitis. Frontiers in Immunology 8, 442 (2017).
  7. Thaler, F. S. et al. Rituximab treatment and long-term outcome of patients with autoimmune encephalitis. Neurology: Neuroimmunology and Neuroinflammation 8, (2021).
  8. Fitch, A. AE Warrior Personal Stories Archives. Autoimmune Encephalitis (2022). Available at: https://autoimmune-encephalitis.org/category/ae-warrior-personal-stories/. (Accessed: 25th October 2022).
  9. Titulaer, M. J. et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: An observational cohort study. Lancet Neurology 12, 157–165 (2013).
  10. Seifert-Held, T. et al. Functional recovery in autoimmune encephalitis: A prospective observational study. Frontiers in Immunology 12, 641106 (2021).
  11. Leypoldt, F., Wandinger, K.-P., Bien, C. G. & Dalmau, J. Autoimmune encephalitis. European Neurological Review 8, 31–37 (2013).
  12. Amy. Amy’s story. The Encephalitis Society (2021). Available at: https://www.encephalitis.info/amys-story. (Accessed: 25th October 2022).

 

 

IAES PNK Partnership logo 500x419 - How does the brain heal from autoimmune encephalitis and why is there so much variability in the healing process?

Click here or the image below to subscribe to our mailing list:

subscribe - Halloween Ideas

Your generous Donations allow IAES to continue our important work and save lives!

 

 

Tabitha Orth 300x218 - How does the brain heal from autoimmune encephalitis and why is there so much variability in the healing process?

 

 

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.

 

guidestar platinum logo 300x300 1 e1605914935941 - How does the brain heal from autoimmune encephalitis and why is there so much variability in the healing process?

 

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.   Trivia Playing cards 3 FB 500x419 - How does the brain heal from autoimmune encephalitis and why is there so much variability in the healing process? 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.   AE Warrior Store 300x200 - How does the brain heal from autoimmune encephalitis and why is there so much variability in the healing process?

Be a part of the solution by supporting IAES with a donation today.

why zebra - Aphasia as a Symptom of Autoimmune Encephalitis
Fatigue and Autoimmune Encephalitis: You’re Not Alone

Fatigue and Autoimmune Encephalitis: You’re Not Alone

by | Nov 29, 2022 | PennNeuroKnow

November 30, 2022 | by Vanessa B. Sanchez, PennNeuroKnow

 

Introduction

Imagine you just pulled out a load of laundry from the dryer, and as you begin to get into the groove of folding clothes, out of nowhere, you have a profound loss of energy (1). What you are experiencing is called fatigue. Fatigue is different from drowsiness or sleepiness. For example, drowsiness is the need for sleep whereas sleepiness is the likelihood of being able to fall asleep (1, 3). To clarify, fatigue is the overwhelming feeling of tiredness, weakness, and a complete lack of energy (3).

Fatigue impacts millions of Americans every day. In fact, about 5 to 10% of visits to primary care doctors in the United States are due to patients reporting fatigue (3). Despite its pervasiveness, fatigue can be experienced differently across individuals. For example, males describe fatigue as feeling tired while females more often describe their fatigue as feeling anxious or depressed (2).

Fatigue is a common symptom of autoimmune encephalitis

Patients with autoimmune encephalitis (AE) describe fatigue as one of their main persistent symptoms, even after recovery (5). It can become so disabling that patients may drop out of school or work, thus negatively impacting their quality of life (6). Dr. Anusha K Yeshokumar, an autoimmune neurologist, conducted two studies to determine the outcomes of survivors of AE in order to find ways to improve patients’ quality of life (5). In both studies, she found that over 60% of patients reported experiencing fatigue (5).  Of these patients, she also found that over 80% of them reported feeling both physical (feeling weak, the need to rest, etc.) and cognitive fatigue (less alert, cannot think clearly, etc.) (5).

A notable finding in Dr. Yeshokumar’s study was that anti-NMDAR AE seems to act differently when it comes to fatigue, such that adults experience it much less than children (5). Another factor that influenced whether patients with AE experienced fatigue was the time of diagnosis and treatment. Anti-NMDAR AE is one of the most well-characterized AEs, so doctors tend to diagnose and treat patients faster than other types of AE. Other types of AE aren’t as well-characterized, which can interfere with a doctor’s ability to properly diagnose and treat patients quickly. Because of this interference, patients who do not get diagnosed as quickly are more likely to experience fatigue. For example, patients with other AEs reported the time from symptom onset to diagnosis and to treatment took almost 300 days while it only took 30 days for patients with anti-NMDAR AE! (5). As doctors and researchers learn more about other AEs, it can hopefully aid in earlier diagnosis and treatment to prevent chronic (≥6 months) fatigue.

Is your brain making you feel fatigued?

Fatigue is often associated with the sickness behavioral response, which occurs when the body tries to cope or fight off an infection (14). Scientists believe that the brain is responsible for this sickness behavioral response (7). In a recent study, scientists explored whether there are certain types of neurons that become activated when an infection occurs and may be responsible for sickness behaviors (7,8). To do so, scientists injected healthy mice with a molecule to induce a bacterial infection and make them sick (7,8). Afterwards, scientists performed a special technique called single-cell RNA sequencing (scRNA-seq) on the brains of mice who did or did not receive the bacterial injection (7,8). scRNA-seq is a widely used tool used to study the identity of different types of cells (To learn more and read about scRNA-seq, check out this Penn Neuro Know article!). By using this sequencing technique, scientists discovered two specific populations of neurons that reside in the brainstem, the part of our brain connected to the spinal cord (7,8). Scientists found that these populations in the brainstem are responsible for several sickness symptoms, like appetite, movement, and body temperature (7,8). Changes in mouse behavior like a reduction in physical activity and/or weight loss are how scientists can make inferences that mice are experiencing fatigue (17). This is because fatigue is often associated with a decline in physical and daily activities.

In another complementary study, a team of scientists found another specialized population of neurons in a brain region called the hypothalamus that are responsible for sickness behaviors like fever and nausea (7,9). These key findings are now pointing scientists in the right direction toward fully understanding these neuronal populations in order to mitigate or prevent sickness behaviors, including fatigue.

Are there other explanations for fatigue?

Another reason why patients experience fatigue is because they may have chronic or relapsing neuroinflammation (5). Neuroinflammation occurs when the body’s immune system is triggered following an infection, or in the case of AE, to attack healthy cells in the brain. The brain has a protective sheath called the blood-brain barrier (BBB), which prevents most infections and foreign invaders from getting to the brain. In the case that infection or inflammation does occur, the body’s immune cells will release a special signal that can pass through the BBB to let neurons and microglia know danger is near. These signals alert a special population of immune cells in the brain, called microglia, that they should begin to defend against infection. Once microglia are alerted, they will activate neighboring neurons. When neurons receive this signal, they become strongly active and communicate with nearby neurons and brain regions (14). Scientists have proposed that this increased neuronal activity is what also contributes to fatigue (14). In the case of AE or chronic neuroinflammation, scientists postulate that because microglia and other immune cells are constantly activated and releasing that special signal, neurons also remain persistently active, and so do feelings of fatigue (14). 

Treatments for chronic fatigue

Doctors can prescribe some medications or over-the-counter drugs that can ease symptoms of chronic fatigue (13). Some doctors might suggest lifestyle changes to help manage and alleviate fatigue, such as practicing good sleep hygiene (i.e., getting a full 8 hours of sleep and keeping a sleep diary) and lifestyle changes (i.e., eating, drinking, exercising, etc.) (15, 16). Despite working for some patients, sometimes medications and lifestyle changes are not enough to alleviate chronic fatigue. In those cases, holistic interventions, like yoga or mindfulness, can also sometimes improve overall quality of life. For example, patients with multiple sclerosis (MS) – another type of autoimmune disease – who practiced yoga for 2 or 4 months reported lower levels of fatigue (11). Other studies have found that MS patients who practiced trait mindfulness (the ability to practice living in the present moment) also reported being able to maintain a higher health-related quality of life (10, 12).

Research studies such as the one by Dr. Yeshokumar are huge steps towards understanding how fatigue impacts survivors of AE and being able to better treat patients. Both scientists and doctors are getting closer to understanding the exact biological mechanisms of fatigue in AE, which will hopefully aid in the development of treatments that target these mechanisms to improve patients’ quality of life.

References:

1-Medline. Fatigue (https://medlineplus.gov/ency/article/003088.htm)

2-Rosenthal, T. C., Majeroni, B. A., Pretorious, R., & Malik, K. (2008). Fatigue: an overview. American family physician, 78(10), 1173-1179.

3-Dukes, J. C., Chakan, M., Mills, A., & Marcaurd, M. (2021). Approach to fatigue: best practice. Medical Clinics, 105(1), 137-148.

4-Son, C. G. (2019). Differential diagnosis between “chronic fatigue” and “chronic fatigue syndrome”. Integrative medicine research, 8(2), 89.

5-Diaz-Arias, L. A., Yeshokumar, A. K., Glassberg, B., Sumowski, J. F., Easton, A., Probasco, J. C., & Venkatesan, A. (2021). Fatigue in survivors of autoimmune encephalitis. Neurology-Neuroimmunology Neuroinflammation, 8(6). 

6-De Bruijn, M. A., Aarsen, F. K., Van Oosterhout, M. P., Van Der Knoop, M. M., Catsman-Berrevoets, C. E., Schreurs, M. W., … & Titulaer, M. J. (2018). Long-term neuropsychological outcome following pediatric anti-NMDAR encephalitis. Neurology, 90(22), e1997-e2005.

7-Hicks, A. I., & Prager-Khoutorsky, M. (2022). Neuronal culprits of sickness behaviours.

8-Ilanges, A., Shiao, R., Shaked, J., Luo, J. D., Yu, X., & Friedman, J. M. (2022). Brainstem ADCYAP1+ neurons control multiple aspects of sickness behaviour. Nature, 1-11.

9-Osterhout, J. A., Kapoor, V., Eichhorn, S. W., Vaughn, E., Moore, J. D., Liu, D., … & Dulac, C. (2022). A preoptic neuronal population controls fever and appetite during sickness. Nature, 1-8.

10-​​Grossman, P., Kappos, L., Gensicke, H., D’Souza, M., Mohr, D. C., Penner, I. K., & Steiner, C. (2010). MS quality of life, depression, and fatigue improve after mindfulness training: a randomized trial. Neurology, 75(13), 1141-1149.

11-Dehkordi, A. H. (2016). Influence of yoga and aerobics exercise on fatigue, pain and psychosocial status in patients with multiple sclerosis: a randomized trial.

12-Mioduszewski, O., MacLean, H., Poulin, P. A., Smith, A. M., & Walker, L. A. (2018). Trait mindfulness and wellness in multiple sclerosis. Canadian Journal of Neurological Sciences, 45(5), 580-582.

13-Cassoobhoy, A. (2020, December 13). Medications used to treat chronic fatigue syndrome (CFS). WebMD. Retrieved September 17, 2022, from https://www.webmd.com/chronic-fatigue-syndrome/medicines-treat-chronic-fatigue-syndrome 

14-Omdal, R. (2020). The biological basis of chronic fatigue: neuroinflammation and innate immunity. Current opinion in neurology, 33(3), 391-396.

15-Encephalitis Society. Managing fatigue after encephalitis.

16- Brazier, Y. (2022, August 10). Fatigue: Why am I so tired, and what can I do about it? Medical News Today. Retrieved August 31, 2022, from https://www.medicalnewstoday.com/articles/248002

17-Wolff, B. S., Raheem, S. A., & Saligan, L. N. (2018). Comparing passive measures of fatigue-like behavior in mice. Scientific reports, 8(1), 1-12.

Photo by Zohre Nemati on Unsplash

 

Check out some yoga TikToks (#yogaTok) that you can do in the comfort of your own home!

 

 

IAES PNK Partnership logo 500x419 - Fatigue and Autoimmune Encephalitis: You're Not Alone

Click here or the image below to subscribe to our mailing list:

subscribe - Halloween Ideas

Your generous Donations allow IAES to continue our important work and save lives!

 

 

Tabitha Orth 300x218 - Fatigue and Autoimmune Encephalitis: You're Not Alone

 

 

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.

 

guidestar platinum logo 300x300 1 e1605914935941 - Fatigue and Autoimmune Encephalitis: You're Not Alone

 

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.   Trivia Playing cards 3 FB 500x419 - Fatigue and Autoimmune Encephalitis: You're Not Alone 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.   AE Warrior Store 300x200 - Fatigue and Autoimmune Encephalitis: You're Not Alone

Be a part of the solution by supporting IAES with a donation today.

why zebra - Aphasia as a Symptom of Autoimmune Encephalitis
Rare and Seronegative Autoimmune Encephalitis

Rare and Seronegative Autoimmune Encephalitis

by | Oct 27, 2022 | Australian Autoimmune Encephalitis Consortium

October 28, 2022 | Written by Dr. Nabil Seery. Edited by Dr Mastura Monif, Ms Tiffany Rushen, Dr Loretta Piccenna, Ms Amanda Wells (consumer representative) and Ms Sasha Ermichina (consumer representative).

A message from IAES Blog Staff:

It is our honor and pleasure to present to all of you an overview of how autoimmune encephalitis can affect cognitive abilities. This overview is by the esteemed team at Monash University in Australia & lead by Dr. Mastura Monif, who is a member of IAES’ Medical Advisory Board.

We are proud to be in collaboration with Dr. Monif and her team in the Australian Autoimmune Encephalitis Consortium Project as we work closely with them to best support AE patients, caregivers and their families. This blog has been facilitated by IAES Support Services coordinator Mari Wagner Davis, with input from IAES volunteers Sasha Ermichina (impacted by GFAP AE) and Amanda Wells (caregiver for her daughter with AE). These IAES representatives provide input from their unique perspectives, helping to educate researchers in the difficulties that patients and families face.

You can find out more about the Australian Autoimmune Encephalitis Consortium and their efforts to help those with AE and their families via the following link:

https://www.monash.edu/medicine/autoimmune-encephalitis

 —-

Rare and Seronegative Autoimmune Encephalitis

Source: Seery N, Butzkueven H, O’Brien TJ, Monif. M. Rare Antibody-Mediated and Seronegative Autoimmune Encephalitis: an Update. Autoimmunity Rev. 2022 May 18;21(7);103118. https://doi.org/10.1016/j.autrev.2022.103118

WHY WE DID THIS WORK

■ Autoimmune encephalitis (AE) is a form of autoimmune disease whereby immune cells in the body inappropriately target components of the nervous system. This causes dysfunction of nerve cells, and in some cases death of these cells, and further produces different clinical symptoms that are reversible. Such symptoms include (but are not limited to) cognitive symptoms, such as difficulties with memory and language, seizures, movement disorders, and psychiatric symptoms.

■ Antibodies are central to the diagnosis of many subtypes of autoimmune encephalitis. Generally, antibodies are proteins produced by the immune system to fight infections. In a proportion of patients with autoimmune encephalitis there can be an abnormal expression of antibodies, where, rather than targeting foreign molecules (e.g. viruses, bacteria), they mistakenly target self-proteins on nerve endings or self-proteins inside the nerve cell or neuron. In up to half of cases, an antibody is not detectable using current available tests or assays. This group of cases is called “seronegative” autoimmune encephalitis, i.e. denoting a lack of antibodies in the serum (a component of a patient’s blood) or cerebrospinal fluid (a clear fluid the surrounds the brain and spinal cord, obtained via a lumbar puncture, a procedure involving a fine needle being inserted in the lower back). ‘Seronegative’ autoimmune encephalitis most likely represents a broader collection of disorders.

■ Over the last two decades, antibody-mediated subtypes of autoimmune encephalitis continue to be discovered, with over ten such forms now recognised. Further, following the respective discovery of such new forms of autoimmune encephalitis, disease mechanisms and clinical features have been revealed. However, seronegative autoimmune encephalitis remains less well characterised, possibly in part to because of its heterogeneous nature – meaning that a variety of diseases forms may be included by the definition.

■ The purpose of our review was to explore advances regarding five rare antibody-mediated forms of autoimmune encephalitis, namely, anti-g-aminobutyric acid B (GABAB) receptor-, anti-a-amino-3hydroxy-5-methyl-4-isoxazolepropinoic receptor- (AMPAR), anti-GABAA receptor-and anti-dipeptidyl-peptidase-like protein-6 (DPPX) encephalitis and IgLON5 disease.

■ We also summarise current research and challenges in relation to ‘seronegative’ autoimmune encephalitis. For a detailed discussion of anti- NMDA autoimmune encephalitis, anti-LGI1 and anti-CASPR2 autoimmune encephalitis refer to (Contemporary advances in anti-NMDAR antibody (Ab)-mediated encephalitis -PubMed (nih.gov) (1) and Contemporary advances in antibody-mediated encephalitis: anti-LGI1 and anti-Caspr2 antibody (Ab)-mediated encephalitides -PubMed (nih.gov)) (2).

WHAT WE FOUND

■ GABAB, AMPAR and GABAA autoimmune encephalitis have common and distinguishing clinical features. These three forms of autoimmune encephalitis are diagnosed by the presence of antibodies found in the blood or cerebrospinal fluid of suspected patients. All three are relatively rare, compared to some other antibody-mediated forms of autoimmune encephalitis such as anti-N-methyl-D-aspartate receptor (NMDAR) and anti-leucine-rich gliomainactivated 1 (LGI1) Ab-mediated encephalitis. GABAA encephalitis in particular is exceedingly rare, with approximately fifty cases reported overall as at a few years ago.

■In these diseases, antibodies target the GABAB, AMPAR and GABAA receptors (proteins present on nerve cell endings), causing neuronal dysfunction. GABAB and GABAA receptors both attract an inhibitory neurotransmitter called GABA. A neurotransmitter is a signalling molecule that helps with communication and transmission of impulses between neurons, and inhibitory neurotransmitters reduce the likelihood a given neuron will generate an electrical signal called an action potential.

■ Seizures in these diseases are a main feature, and may be particularly non-responsive to conventional anti-seizure treatment. Furthermore, cognitive and psychiatric symptoms are common in all three of these subtypes of autoimmune encephalitis. GABAB and AMPAR subtypes may have similar findings identified on MRI imaging of the brain, with inflammation and swelling seen in part of the brain called the mesial temporal lobe. The mesial temporal lobe is an area of the brain important for memory, emotion and behaviour.

■ The diagnosis of autoimmune encephalitis invariably necessitates that clinicians investigate for the possibility of a tumour (e.g. lung cancer, thyroid cancer, breast cancer) that may have triggered the disease. Treating the tumour or cancer where feasible and as promptly as possible has been linked to improvements in autoimmune encephalitis symptoms. Similarly, the presence of neurological symptoms, if preceding a cancer diagnosis, may allow for this to be facilitated more quickly than might have been the case otherwise, which may help afford a better chance of more effectively treating the underlying cancer.

■ In approximately half of patients diagnosed with GABAB encephalitis, an underlying tumour is found, most often small-cell lung cancer. In AMPAR encephalitis, almost two-thirds of patients have an underlying tumour, with thymus tumours and lung cancer most common. In GABAA encephalitis, approximately one third of patients have also been shown to have an underlying tumour.

■ DPPX encephalitis and IgLON5 disease are two rare and somewhat clinically unique forms of autoimmune encephalitis. In DPPX encephalitis, patients commonly present with profound weight loss or diarrhoea and have features of central-nervous system hyperexcitability. This is a state where the brain has increased responsiveness to a variety of external stimuli. In DPPX encephalitis, features attributed to CNS hyperexcitability include myoclonus, or rapid, involuntary muscle jerks, and tremor. IgLON5 disease on the other hand also has unique clinical features, such as a variety of sleep disturbances.

■ Seronegative autoimmune encephalitis overall requires further study and description to identify potential antibodies which may be the cause. Seronegative limbic encephalitis is a form of seronegative autoimmune encephalitis, where the limbic structures in the brain are affected. In this subset of the disease inflammation is observed in the mesial temporal lobes using Magnetic Resonance Imaging (MRI). Seronegative limbic encephalitis is typically seen in older patients, with conventional antibody testing not revealing an antibody. Patients typically have memory impairment, with or without psychiatric symptoms and seizures, and are treated with medications that lower effects of the immune system, as in other forms of autoimmune encephalitis.

HOW CAN WE USE THIS RESEARCH

■ These findings are intended to help researchers and clinicians better understand seronegative and rare forms of autoimmune encephalitis. By bringing this information together, it can assist with improving diagnosis and assisting with early treatment by clinicians.

■ It should be noted that antibody-related forms of autoimmune encephalitis are usually diagnosed as “possible autoimmune encephalitis” prior to the availability of antibody results, which can take up to a period of weeks. A diagnosis of autoimmune encephalitis is based on broad criteria involving consideration of a patient’s symptoms and test results, including MRI, electroencephalogram (EEG – a measure of the electrical activity of the brain) and cerebrospinal fluid biopsy results, combined with the exclusion other diseases, for example, viruses that could mimic the observed symptoms.

■ Prompt diagnosis of autoimmune encephalitis, and prompt exclusion of other causes such as viral encephalitis is very important, as there is a growing body of evidence indicating that earlier initiation of immune-lowering treatment for autoimmune encephalitis may be able to facilitate better recovery.

■ The seronegative form of autoimmune encephalitis can represent a large proportion of autoimmune encephalitis patients overall so its understanding is crucial for improvements in clinical care.

■ Regarding very rare subtypes of autoimmune encephalitis, an understanding of the characteristic features of these rare entities is crucial in forming a diagnostic workup plan. Further, awareness of the features of some of these rarer subtypes can ensure prompt and accurate investigation of underlying tumours. Knowledge of rarer subtypes may also be able to inform clinicians and patients about the possible outcomes of these conditions to inform day to day discussions with patients and their caregivers.

—-

For more information and resources from Dr. Monif and her group at the Australian Autoimmune Encephalitis Consortium Project, visit this link here. To download a plain language PDF of the paper summarized in this blog, click the button below:

Download Plain Language Summary

 

Click here or the image below to subscribe to our mailing list:

subscribe - Halloween Ideas

Your generous Donations allow IAES to continue our important work and save lives!

 

Tabitha Orth 300x218 - Rare and Seronegative Autoimmune Encephalitis

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.

guidestar platinum logo 300x300 1 e1605914935941 - Rare and Seronegative Autoimmune Encephalitis

 

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.   Trivia Playing cards 3 FB 500x419 - Rare and Seronegative Autoimmune Encephalitis 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.   AE Warrior Store 300x200 - Rare and Seronegative Autoimmune Encephalitis

Be a part of the solution by supporting IAES with a donation today.

why zebra - Aphasia as a Symptom of Autoimmune Encephalitis
Rare and Seronegative Autoimmune Encephalitis

Epilepsy and Autoimmune Encephalitis

by | Oct 11, 2022 | Australian Autoimmune Encephalitis Consortium

October 12, 2022 | Written by Dr. Robb Wesselingh. Edited by Dr Mastura Monif, Ms Tiffany Rushen, Dr Loretta Piccenna, Ms Amanda Wells (consumer representative) and Ms Sasha Ermichina (consumer representative).

A message from IAES Blog Staff:

It is our honor and pleasure to present to all of you an overview of how autoimmune encephalitis can affect cognitive abilities. This overview is by the esteemed team at Monash University in Australia & lead by Dr. Mastura Monif, who is a member of IAES’ Medical Advisory Board.

We are proud to be in collaboration with Dr. Monif and her team in the Australian Autoimmune Encephalitis Consortium Project as we work closely with them to best support AE patients, caregivers and their families. This blog has been facilitated by IAES Support Services coordinator Mari Wagner Davis, with input from IAES volunteers Sasha Ermichina (impacted by GFAP AE) and Amanda Wells (caregiver for her daughter with AE). These IAES representatives provide input from their unique perspectives, helping to educate researchers in the difficulties that patients and families face.

You can find out more about the Australian Autoimmune Encephalitis Consortium and their efforts to help those with AE and their families via the following link:

 

https://www.monash.edu/medicine/autoimmune-encephalitis

 —-

Epilepsy and Autoimmune Encephalitis

Publication:

Source – Wesselingh, R., Broadley, J., Buzzard, K., Tarlinton, D., Seneviratne, U., Kyndt, C., Stankovich, J., San􀄀lippo, P., Nesbitt, C., D’Souza, W., Macdonell, R., Butzkueven, H., O’Brien, T. J., & Monif, M. (2022). Prevalence, risk factors, and prognosis of drugresistant epilepsy in autoimmune encephalitis. Epilepsy & behavior: E&B, 132, 108729. Advance online publication. https://doi.org/10.1016/j.yebeh.2022.108729

 —-

Seizures (or sudden, uncontrolled electrical disturbances in the brain) are a common initial neurological symptom that occurs in people with autoimmune encephalitis. In autoimmune encephalitis a person’s immune system mistakenly targets different proteins in their brain causing damage and inflammation. For some people, the seizures can progress to very severe and ongoing seizures called status epilepticus, requiring treatment to stop them happening. While some patients will stop having seizures after immune system suppressing treatment, others will continue to have seizures that do not respond, even to increasing amounts of anti-seizure medications. This is known clinically as treatment- or drug-resistant epilepsy.  Drug-resistant epilepsy has a significant impact on the quality of life of people with autoimmune encephalitis. We currently do not know why some patients with autoimmune encephalitis develop drug-resistant epilepsy whilst others do not.

It is important for doctors to be able to predict how and why people with autoimmune encephalitis develop drug-resistant epilepsy because it is a disabling complication that may be preventable. For this research, we wanted to find out answers to following questions –

  1. How common is drug-resistant epilepsy after autoimmune encephalitis?
  2. What are the risk factors for the development of drug-resistant epilepsy after autoimmune encephalitis?
  3. In the early part the disease, can the use of EEG tell us about a person’s likelihood of developing drug-resistant epilepsy?
  4. Can we use this information to predict which patients with autoimmune encephalitis are going to develop drug resistant epilepsy?

How we did this work

We looked through the medical records of seven hospitals in Victoria (Australia) for people who met the diagnosis of autoimmune encephalitis and had an EEG when they first became unwell. Two hundred and eight patients were identified and selected for analysis. We then collected available data from 69 patients of their symptoms, seizures, treatment, and whether they developed drug-resistant epilepsy at 12 months after their initial illness.

We analysed EEGs from patients to find any brain wave irregularities or signatures (called EEG biomarkers) that were more common in those with autoimmune encephalitis who developed drug-resistant epilepsy than those that did not develop drug-resistant epilepsy. Finally, we combined all the factors and created a tool that doctors can use to predict an individual’s risk of developing drug-resistant epilepsy after autoimmune encephalitis.

What were the interesting things we found

  • We found that it was not uncommon to develop drug-resistant epilepsy after autoimmune encephalitis. It occurred in 16% of patients with autoimmune encephalitis in our analysis.
  • We also identified that a key risk factor for the development of drug-resistant epilepsy after autoimmune encephalitis was people who experienced status epilepticus 
  • On EEG, large spikes of abnormal electrical activity called ‘periodic discharges’ combined with their specific location in the brain can predict the development of drug-resistant epilepsy after autoimmune encephalitis.

epilepsy ae 500x266 - Continuing My Way Up The Slippery Slope: A Poem

Figure 1: This figure shows a summary of our findings with 208 patients with autoimmune encephalitis, 16% had severe form of seizures (SE; status epilepticus), 75% of patients had 1 or more seizures, and 25% did not have seizures at their initial admission. Then after 12 months follow up, 16% of patients who completed follow up, had DRE (drug resistant epilepsy), and 33% of the patients were on anti-seizure medications (ASM) and 48% did not require ASMs.

 

What do these findings mean?

The research could help clinicians to –

  1. Identify those patients with autoimmune encephalitis at risk of developing drug-resistant epilepsy and potentially change their treatment strategy (creating a risk assessment tool to use in practice), and
  1. Address risk factors such as status epilepticus with the goal to try and reduce the long-term risk of drug-resistant epilepsy.

 —-

For more information and resources from Dr. Monif and her group at the Australian Autoimmune Encephalitis Consortium Project, visit this link here. To download a plain language PDF of the paper summarized in this blog, click the button below:

Download Plain Language Summary

 

Click here or the image below to subscribe to our mailing list:

subscribe - Halloween Ideas

Your generous Donations allow IAES to continue our important work and save lives!

 

Tabitha Orth 300x218 - Epilepsy and Autoimmune Encephalitis

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.

guidestar platinum logo 300x300 1 e1605914935941 - Epilepsy and Autoimmune Encephalitis

 

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.   Trivia Playing cards 3 FB 500x419 - Epilepsy and Autoimmune Encephalitis 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.   AE Warrior Store 300x200 - Epilepsy and Autoimmune Encephalitis

Be a part of the solution by supporting IAES with a donation today.

why zebra - Aphasia as a Symptom of Autoimmune Encephalitis
Movement disorders as a window into the diversity of autoimmune encephalitis

Movement disorders as a window into the diversity of autoimmune encephalitis

by | Sep 13, 2022 | PennNeuroKnow

September 14, 2022 | by Catrina Hacker, PennNeuroKnow

Whether it’s walking to the grocery store or hugging a friend, movement is a central part of how we interact with the world. We don’t usually think about how we’re able to move, but every motion is part of a beautifully efficient process that coordinates a complicated network of cells across the nervous system. When neurological disorders disrupt this coordination, the efficiency of our motor system breaks down, which can lead to a variety of movement disorders and produce a broad range of symptoms. Movement disorders are a common symptom across the many types of autoimmune encephalitis (AE) and can be especially important to the diagnosis of AE in children.

Learning the language of movement disorders

The scientific literature is littered with dozens of specialized terms doctors use to describe movement-related disorders. For doctors, these terms are helpful because they can precisely describe specific symptoms that help them distinguish between different diagnoses, but they can be intimidating to non-medical readers. To begin, let’s break down a few important terms describing the disorders most common in various types of AE. Please note that this is not an exhaustive list and is only meant to capture some of the most common movement disorders that can result from common types of AE. (Click the name of the disorder to watch a Youtube video demonstrating some of these symptoms.)

Ataxia. Ataxia describes difficulty balancing and coordinating movements. In the most classic presentation of ataxia patients struggle with walking and running, particularly in situations that require more coordination such as walking up and down stairs1. Patients with ataxia can have a high risk of falling and in some cases they might have difficulty coordinating the movements necessary for speaking or writing2. One type of ataxia is thought to be caused by degeneration of neurons in a brain region known to be important for movement called the cerebellum1,2.

Chorea. Patients with chorea make involuntary, random movements. These brief and random movements are not repetitive or rhythmic but do appear to flow from one muscle to the next3. Chorea can occur in any muscle group, ranging from fingers and toes to facial movements. Interestingly, chorea subsides when patients are asleep4. Chorea is associated with too much activity of a neurotransmitter called dopamine that plays an important role in coordinating and initiating movement3,4.

Dystonia. Patients with dystonia experience involuntary muscle contractions that result in abnormal postures and repetitive movements. These contractions can occur anywhere on the body and are often painful. Like ataxia, dystonia can cause problems with speech and handwriting. In addition, patients with dystonia might experience foot cramps or drag their foot after prolonged exercise5.

Myoclonus. Myoclonus is a broad term describing sudden, involuntary jerking of muscles. This often involves twitching of a muscle followed by relaxation. If you’ve ever jerked awake while drifting off to sleep you’ve experienced a benign myoclonic jerk (this is not worrisome as an isolated event). Myoclonic jerks can occur on their own or be associated with different disorders6. The movements in myoclonus are quick and simple, while the movements in chorea tend to be slower and continuous. (Hear directly from a patient about her experience with dystonia and myoclonus here)

Movement disorders across different types of autoimmune encephalitis

While many types of AE can result in movement disorders, some subtypes have unique symptoms that distinguish them from others. Sometimes movement disorders are one of the most prominent symptoms to present themselves, whereas in other cases they may be more subtle and secondary to other psychiatric symptoms. Here we will discuss some of the subtypes of AE that most commonly result in movement disorders.

Several movement disorders often present together in patients with anti-NMDAR AE, the most common AE. Chorea and dystonia are observed in up to 90% of Anti-NMDAR patients7. While they can affect all limbs, in anti-NMDAR encephalitis they most characteristically affect the face and mouth8. In some cases these might be the first signs of the disease, so a clinician should consider the possibility of AE when patients visit the clinic with complaints of movement-related symptoms7.

Movement disorders are some of the most common symptoms of CASPR2-antibody associated encephalitis. Ataxia is observed in up to a third of patients and can be the only presenting symptom at disease onset, with other symptoms developing later7. The ataxia in CASPR2-encephalitis patients often manifests as a strong gait disturbance8 that occurs in brief, but frequent, bursts7. CASPR2-encephalitis can also present with a distinct form of myoclonus that distinguishes it from other kinds of AE. This form of AE is most common in elderly men9, and myoclonus of the lower limbs is often observed when patients are walking or standing. Spinal myoclonus leading to spasms around the abdomen has also been observed in CASPR2-encephalitis patients7. Finally, in some cases chorea is a prominent movement-related symptom of CASPR2-encephalitis7.

IGLON5-antibody associated encephalitis can also present with many movement disorders. While the best indicator of IGLON5-encephalitis is sleep disorders, some patients have also been reported to have chorea7. Another movement disorder reported in some IGLON5-encephalitis patients is axial rigidity, or rigidity in the trunk and hips. These movement disorders can make it difficult for patients with IGLON5-encephalitis to walk and balance and can put them at risk of falling8.

Many other types of AE are associated with movement disorders including (but not limited to) GlyR-, DDPX-, LGI1-, and mGluR1-antibody associated encephalitis7,8. It is important to note that although movement disruptions are common in many types of AE, they are rarely the only symptom and are not diagnostic on their own7,8,10. Instead, they can serve as one of many clues leading doctors toward a correct diagnosis. The neural explanation for how each type of AE leads to these movement disorders is not well understood. Determining the biological basis of the relationship between AE and movement disorders is an important area for future research that might help us to better understand these distinct subtypes of AE.

Movement disorders in children and adults with autoimmune encephalitis

In addition to distinguishing different types of AE, movement disorders are proving to be an especially important diagnostic tool for children with AE. Movement disorders can be observed in both children and adults, but they are more common in children, particularly those with anti-NMDAR AE. The presentation of anti-NMDAR AE in adults is now well understood and typically involves psychiatric symptoms and cognitive impairment as well as the movement disorders described above. The presentation of anti-NMDAR AE in children isn’t as well documented, but diverges from adults in that it more often includes seizures and movement disturbances7,10,11.

In many cases, movement disturbances are the first or only presenting symptom in children with anti-NMDAR AE. One set of case studies showed that four young patients eventually diagnosed with anti-NMDAR AE all initially presented with difficulties walking or coordinating movement10. Another study considered 50 cases of children with anti-NMDAR AE and found that motor deficits including dystonia of the hands and feet are key in diagnosing focal seizures that often accompany AE in these patients11. The initial presentation of anti-NMDAR AE can be ambiguous, and treatment is often delayed because a diagnosis is not immediately made. The presence of movement disorders and other disturbances (e.g., those accompanying seizures) along with other symptoms could be key signs to consider a diagnosis of AE in children10.

The diversity of movement disorders in various types of AE mirrors the diversity of the diseases themselves. Whether in distinguishing subtypes of AE or diagnosing children, they are a powerful spotlight under which the diversity of AE can be interrogated. Despite our growing understanding of how movement disorders can be used to diagnose various types of AE, there is still very little understanding of why different types of AE cause different types of movement disorders. Future work can leverage these known differences in movement disorders associated with different types of AE to better understand their biological basis and hopefully develop better treatments and cures. 

References

  1. Ataxias and Cerebellar or Spinocerebellar Degeneration | National Institute of Neurological Disorders and Stroke. https://www.ninds.nih.gov/health-information/disorders/ataxias-and-cerebellar-or-spinocerebellar-degeneration.
  2. Kuo, S.-H. Ataxia: Contin. Lifelong Learn. Neurol. 25, 1036–1054 (2019).
  3. Chorea | National Institute of Neurological Disorders and Stroke. https://www.ninds.nih.gov/health-information/disorders/chorea.
  4. Bhidayasiri, R. Chorea and related disorders. Postgrad. Med. J. 80, 527–534 (2004).
  5. Dystonia | National Institute of Neurological Disorders and Stroke. https://www.ninds.nih.gov/health-information/disorders/dystonia.
  6. Myoclonus | National Institute of Neurological Disorders and Stroke. https://www.ninds.nih.gov/health-information/disorders/myoclonus.
  7. Gövert, F. et al. Antibody-related movement disorders – a comprehensive review of phenotype-autoantibody correlations and a guide to testing. Neurol. Res. Pract. 2, 6 (2020).
  8. Uy, C. E., Binks, S. & Irani, S. R. Autoimmune encephalitis: clinical spectrum and management. Pract. Neurol. 21, 412–423 (2021).
  9. van Sonderen, A. et al. The clinical spectrum of Caspr2 antibody–associated disease. Neurology 87, 521–528 (2016).
  10. Yeshokumar, A. K., Sun, L. R., Klein, J. L., Baranano, K. W. & Pardo, C. A. Gait Disturbance as the Presenting Symptom in Young Children With Anti-NMDA Receptor Encephalitis. Pediatrics 138, e20160901 (2016).
  11. Favier, M. et al. Initial clinical presentation of young children with N-methyl- d -aspartate receptor encephalitis. Eur. J. Paediatr. Neurol. 22, 404–411 (2018).

 

 

 

IAES PNK Partnership logo 500x419 - Movement disorders as a window into the diversity of autoimmune encephalitis

Click here or the image below to subscribe to our mailing list:

subscribe - Halloween Ideas

Your generous Donations allow IAES to continue our important work and save lives!

 

 

Tabitha Orth 300x218 - Movement disorders as a window into the diversity of autoimmune encephalitis

 

 

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.

 

guidestar platinum logo 300x300 1 e1605914935941 - Movement disorders as a window into the diversity of autoimmune encephalitis

 

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.   Trivia Playing cards 3 FB 500x419 - Movement disorders as a window into the diversity of autoimmune encephalitis 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.   AE Warrior Store 300x200 - Movement disorders as a window into the diversity of autoimmune encephalitis

Be a part of the solution by supporting IAES with a donation today.

why zebra - Aphasia as a Symptom of Autoimmune Encephalitis
Rare and Seronegative Autoimmune Encephalitis

Using Electroencephalogram for quicker diagnosis and prediction of the likely course for patients with Autoimmune Encephalitis

by | Jul 26, 2022 | Australian Autoimmune Encephalitis Consortium


July 27, 2022 | by Dr. Robb Wesselingh

A message from IAES Blog Staff:

It is our honor & pleasure to present to all of you an overview of the use of an Electroencephalogram or EEG for diagnosis and prediction in the treatment of Autoimmune Encephalitis by the esteemed team at Monash University in Australia & lead by Dr. Mastura Monif. The International Autoimmune Encephalitis Society is proud to be in collaboration with Dr. Monif and her team in the Australian Autoimmune Encephalitis Consortium Project. Dr. Monif is on the board of directors for IAES and we work closely with them to best support AE patients, caregivers and their families. You can find out more about the team and their efforts to help those with AE and their families via the following link:

https://www.monash.edu/medicine/autoimmune-encephalitis

 —-

Using Electroencephalogram for quicker diagnosis and prediction of the likely course for patients with Autoimmune Encephalitis

Publication:

R Wesselingh, J Broadley, K Buzzard, D Tarlinton, U Seneviratne, C Kyndt, J Stankovich, P Sanfilippo, C Nesbitt, W D’Souza, R Macdonell, H Butzkueven, TJ O’Brien, M Monif, Electroclinical biomarkers of autoimmune encephalitis, Epilepsy & Behaviour, 2022;128: 108571. https://doi.org/10.1016/j.yebeh.2022.108571

 —-

Autoimmune encephalitis (AE) is a brain inflammation disorder caused by antibodies. A person’s immune system mistakenly targets different proteins in their brain causing damage and inflammation. This can result in different neurological symptoms including seizures (sudden, uncontrolled electrical disturbances in the brain) and memory problems. Autoimmune encephalitis can be classified into different subtypes based on the brain protein targeted by the antibodies produced. The most common subtypes are anti-NMDAR autoimmune encephalitis, anti-LGI-1 autoimmune encephalitis and seronegative autoimmune encephalitis (in which there is no identified antibody). While treatment is effective and available, the diagnosis of autoimmune encephalitis is not straightforward. Also, knowing which patients need more intensive treatment is tricky.

Patients thought to have autoimmune encephalitis usually have a few clinical tests to confirm the diagnosis. They include brain magnetic resonance imaging (MRI), an electroencephalogram (EEG), and blood or cerebrospinal fluid tests to analyse the presence of inflammation. The EEG is a procedure that measures brain electrical activity (brain waves) by using electrodes placed on the scalp. It can show different patterns or irregularities depending on the person’s health state. For example, an EEG can show seizure activity, or it can indicate drowsy or comatose states. In some situations, it can also show very subtle changes that could be useful in our understanding of autoimmune encephalitis and guiding management. It is important for patients with suspected autoimmune encephalitis to have a diagnosis as soon as possible because earlier treatment leads to better long-term recovery. But doing multiple clinical tests takes time, some can be invasive or may only be available in certain centres. For this research, we wanted to find out answers to following –

  1. Can we use an EEG to identify different types of Autoimmune Encephalitis?
  2. In the early part the disorder, can the EEG tell us about a person’s likely course in the long-term (outcomes)?

How we did this work

We looked through the medical records of seven hospitals in Victoria, Australia for people who had possible autoimmune encephalitis and had an EEG when they first became unwell. Overall, 208 patients were identified and selected for our analysis. We collected data from 131 patients of their symptoms, seizures, treatment, and their ability to return to normal day-to-day living. Key clinical characteristics of the patients can be seen below:

monash eegpng - Using Electroencephalogram for quicker diagnosis and prediction of the likely course for patients with Autoimmune Encephalitis

We analysed EEGs from patients to find any brain wave irregularities or signatures (called biomarkers) that would show different subtypes of autoimmune encephalitis. Other EEGs were analysed that could predict which patients might have impaired functional outcomes in the long term.

What were the interesting things we found

  • We identified four specific brain wave signatures or biomarkers that were associated with one type of autoimmune encephalitis called anti-NMDAR autoimmune encephalitis.
  • We also found a disruption of the normal electrical activity of the brain that was more common in patients who had significant functional disability on discharge from hospital.
  • Large spikes of abnormal electrical activity called periodic discharges were seen in patients who ended up having long-term impacts on their day-to-day functioning.

What do these findings mean?

The brain wave signatures or biomarkers we identified can be useful for clinicians to recognise and use in practice as part of diagnosis and provide targeted treatment. 

The research could help clinicians to –

  1. More quickly identify the type of autoimmune encephalitis a patient has and provide a specific treatment strategy, and
  1. Recognise patients with autoimmune encephalitis who are likely to have more long-term functional disability due to their illness.

 —-

For more information and resources on anti-NMDAr encephalitis, visit this link here. To download a plain language PDF of the paper summarized in this blog, click the button below:

Download Plain Language Summary

 

Click here or the image below to subscribe to our mailing list:

subscribe - Halloween Ideas

Your generous Donations allow IAES to continue our important work and save lives!

 

Tabitha Orth 300x218 - Using Electroencephalogram for quicker diagnosis and prediction of the likely course for patients with Autoimmune Encephalitis

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.

guidestar platinum logo 300x300 1 e1605914935941 - Using Electroencephalogram for quicker diagnosis and prediction of the likely course for patients with Autoimmune Encephalitis

 

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.   Trivia Playing cards 3 FB 500x419 - Using Electroencephalogram for quicker diagnosis and prediction of the likely course for patients with Autoimmune Encephalitis 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.   AE Warrior Store 300x200 - Using Electroencephalogram for quicker diagnosis and prediction of the likely course for patients with Autoimmune Encephalitis

Be a part of the solution by supporting IAES with a donation today.

why zebra - Aphasia as a Symptom of Autoimmune Encephalitis
Rare and Seronegative Autoimmune Encephalitis

An overview of N-methyl D-aspartate receptor (NMDAR) antibody-associated encephalitis

by | May 10, 2022 | Australian Autoimmune Encephalitis Consortium

May 11, 2022 | by Seery N, Butzkueven H, O’Brien TJ, Monif M.

A message from IAES Blog Staff:

It is our honor & pleasure to present to all of you an overview of anti-NMDAR Autoimmune Encephalitis by the esteemed team at Monash University in Australia & lead by Dr. Mastura Monif. The International Autoimmune Encephalitis Society is proud to be in collaboration with Dr. Monif and her team in the Australian Autoimmune Encephalitis Consortium Project. Dr. Monif is on the board of directors for IAES and we work closely with them to best support AE patients, caregivers and their families. You can find out more about the team and their efforts to help those with AE and their families via the following link: https://www.monash.edu/medicine/autoimmune-encephalitis

 —-

An overview of N-methyl D-asparate receptor (NMDAR) antibody-associated encephalitis

Contemporary advances in anti-NMDAR antibody (Ab)-mediated encephalitis, Autoimmunity Reviews, April 2022, Volume 21, Issue 4, https://doi.org/10.1016/j.autrev.2022.103057

WHY WE DID THIS WORK:

  • N-methyl D-aspartate receptor (NMDAR) antibody-associated encephalitis, or anti-NMDAR encephalitis is a type of autoimmune encephalitis. Autoimmune encephalitis occurs when parts of the body’s immune system inappropriately attack certain components of nerve cells in the brain. Anti-NMDAR encephalitis is one of the most common defined types of autoimmune encephalitis. Young people who are on average 21 years of age, and females, experience the illness most commonly. But it can occur in older adults (over 45 years) and in young children (less than 12 years), where a relatively higher number of patients are males.
  • To make a diagnosis, doctors record key symptoms (e.g. memory issues, personality change, changes to behaviour alteration, or seizures) and clinical features from tests. The detection of antibodies that bind the receptor (NMDAR) from a patient’s blood or cerebrospinal fluid (fluid that cushions the brain and spinal cord) are also used to confirm the diagnosis of anti-NMDAR encephalitis. Antibodies are proteins produced by the immune system that in normal circumstances have a role in fighting infections. In certain autoimmune diseases, antibodies, along with other parts of the immune system, target normal components of a healthy individual.
  • Anti-NMDAR encephalitis can be treated using medications that selectively reduce components of the immune system, but as the illness is different from person to person, it is challenging to both diagnose and manage. The use of biological markers, or biomarkers (proteins, cells or other characteristics that can generally be detected via a certain test and are association with a particular disease), may be particularly useful for the diagnosis and assessment of how effective treatment is to manage a patient’s illness. Accurate and specific biomarkers for anti-NMDAR encephalitis still do not exist.
  • We did this update to collect the latest research findings from the field to inform researchers and clinicians who manage this condition and have a keen interest.

WHAT WERE THE THINGS WE DISCOVERED?

  • The N-methyl D-aspartate receptor (NMDAR) belongs to a group called glutamate-gated ionotropic receptors. These receptors are mostly located in a region of the brain called the hippocampus more so than other regions, and assist in excitatory transmission of nerve cells. In anti-NMDAR encephalitis, antibodies target a part of the receptor called GluN1.Anti-NMDAR antibodies exist in the serum part of blood and the cerebrospinal fluid.
  • Biomarkers in cerebrospinal fluid that have been identified include B-cell and T-cell chemokines, which are molecules that serve to attract particular white cells to a given part of the body (in particular, CXCL13 and CXCL10), interferon gamma, tumor necrosis factor alpha and interleukins (in particular 6, 7, 10 and 17-A). The levels of certain of these biomarkers were found to also coincide with poor long-term outcomes in patients.

TRIGGERS OF ANTI-NMDAR ENCEPHALITIS:

  • Two known triggers for anti-NMDAR encephalitis are the presence of an ovarian teratoma (an unusual type of tumour that can express nervous tissue) and less commonly, a viral infection of the brain called HSV-encephalitis.
  • Other than these two triggers it is less understood what causes the illness. At a molecular level, patient antibodies induce complex changes to the nerves by disrupting the functioning of the receptor. These findings may explain the variety of symptoms that patients experience, and varying and often impressive degrees of recovery.

CLINICAL FEATURES:

  • The diagnosis of the disease is not always straightforward. Symptoms and other clinical features may overlap with other diseases, and sometimes, at least in the blood, antibodies to the receptor may be seen without the disease itself. A broad range of clinical features exists in anti-NMDAR encephalitis. Patients can experience the following, which may change over time –
      • Changes in behaviour and hallucinations (psychiatric symptoms)
      • Difficulties in mental function (cognitive impairment)
      • Seizures
      • Abnormal movements and
      • Irregularities of the function of the autonomic nervous system (e.g. temperature, heart rate and breathing).
  • Therefore, detection of certain proteins and molecules in the blood or spinal fluid may assist in the diagnosis of the disease, and its management. A variety of candidates have been explored, but so far, generally remain limited in their use in clinical practice.

TREATMENT:

  • The cornerstone of treatment is suppression of the immune system. Research has shown that earlier treatment results in a better long-term outcome.
  • Exciting new treatment options are emerging, but research studies for these treatments are limited to relatively small numbers of patients and their approval for use by government therapeutic agencies is still awaiting. Therefore, we advise clinicians making the decision to use new therapies be made on based on each individual patient’s situation. 

WHAT DO THE FINDINGS MEAN?

  • This research can help clinicians understand how the illness progresses at the cellular and molecular level, its symptoms, the results of supportive tests (e.g. spinal fluid and MRI) and treatment options, and highlight areas of progress and needs in the current research.
  • Most patients will have some degree of recovery in their illness following appropriate treatment, but some symptoms can persist, particularly issues in mental function. Cognitive rehabilitation and follow up with psychiatry and psychology and in some cases antipsychotic medication, anti-depressants and mood stabilizers maybe warranted.

monif group - An overview of N-methyl D-aspartate receptor (NMDAR) antibody-associated encephalitis

2021 Monif group L-R – Paul Sanfilippo, Nabil Seery, Katrina Kan, Robb Wesselingh, William O’Brien, Tiffany Rushen, Mastura Monif (Group Leader), Tracie Tan, Sher Chim Ting, Sarah Griffith, Andrea Muscat.

 

For more information and resources on anti-NMDAr encephalitis, visit this link here. To download a plain language PDF of the paper summarized in this blog, click the button below:

Download Plain Language Summary

 

Click here or the image below to subscribe to our mailing list:

subscribe - Halloween Ideas

Your generous Donations allow IAES to continue our important work and save lives!

guidestar platinum logo 300x300 1 e1605914935941 - An overview of N-methyl D-aspartate receptor (NMDAR) antibody-associated encephalitis

 

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.   Trivia Playing cards 3 FB 500x419 - An overview of N-methyl D-aspartate receptor (NMDAR) antibody-associated encephalitis 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.   AE Warrior Store 300x200 - An overview of N-methyl D-aspartate receptor (NMDAR) antibody-associated encephalitis

Be a part of the solution by supporting IAES with a donation today.

why zebra - Aphasia as a Symptom of Autoimmune Encephalitis
Blood, Sweat, and Clusterin

Blood, Sweat, and Clusterin

by | Jan 24, 2022 | PennNeuroKnow

January 26, 2022 | by Nitsan Goldstein, New insights into the link between exercise and improved cognition

If you’ve been following the developments in COVID-19 treatments over the last year, you’ve probably heard of monoclonal antibodies being used to treat people with severe cases of COVID. Monoclonal antibodies are produced and circulated through the blood when your body fights off an infection. Scientists have figured out how to extract these antibodies from the blood of patients who have recovered from COVID and inject them into patients that are in earlier stages of the disease. While treatments like these are certainly amazing medical feats, it is not all that surprising that contents from the blood of a person who has successfully fought off an infection might help someone else fight the same virus. It turns out, though, that antibodies are not the only proteins circulating in your blood that could improve someone’s health.

We’ve known for hundreds of years that certain qualities about a person make them more or less likely to have strong cognitive skills like memory. Being young, for example, means your memory is likely strong while being older or suffering from diseases like Alzheimer’s means your memory is weaker. Another such factor is the degree to which you exercise. Exercise improves cognitive skills and can help improve memory in people suffering from dementia. For many years, scientists have asked how these factors actually improve brain function. If we can figure out how things like youth and exercise improve memory, perhaps we can use those same pathways to develop treatments for dementia and related disorders.

In 2014, a study was published showing that simply taking blood from young mice and infusing it into older mice could improve the older mice’s performance on memory tasks1. This result was exciting because it suggested that not only could memory impairments of older mice be reversed, but also that they could be reversed by some molecule that was circulating in the blood of young mice. This month, the same group published another study showing that much like the blood of young mice, the blood of mice that had been exercising regularly could also improve other mice’s ability to perform a memory task2. Recent technological advancements allowed them to identify one of the specific proteins in the blood that was mediating the effects in the brain.

The researchers started by infusing plasma, or the liquid part of blood, that was taken from mice that had access to a running wheel for 28 days into mice that did not have access to a wheel. They found that sedentary mice that received plasma infusions from exercised mice (1) performed better on memory tasks, (2) displayed increased neurogenesis, a process believed to be important for memory, and (3) showed evidence of decreased inflammation in the brain. This last finding was intriguing considering the negative impact neuroinflammation can have on learning and memory and the strong link between neurodegenerative diseases like Alzheimer’s and a heightened inflammatory state3,4.

To further probe the relationship between inflammation and memory, the group decided to inject an inflammatory agent and measure changes in the brain with or without plasma taken from exercised mice. They focused on the hippocampus, a region that is crucial for the formation of memories and is prone to degeneration in neurodegenerative diseases. The scientists examined the changes in gene expression or the proteins that will be produced by cells in the hippocampus, after injecting mice with lipopolysaccharide (LPS), which causes an inflammatory response. LPS injection caused changes in gene expression in the hippocampus, but many of these changes were reversed after treatment with plasma from exercised mice. Next, the researchers wanted to pinpoint the protein or proteins in the blood that are responsible for reversing these LPS-induced changes in gene expression. After identifying several candidate proteins, they repeated the experiment, only this time some mice got plasma where one of the candidate proteins was removed before the infusion. They found that one protein, in particular, clusterin, was essential for the beneficial effects of exercised plasma on neuroinflammation. When clusterin was removed from exercised plasma, many of the effects on LPS-induced inflammation in the hippocampus were gone. Even more convincing, the researchers found that injecting clusterin alone was able to reverse some neuroinflammation caused by LPS.

So what are we waiting for? How can we get our hands on clusterin so that we can reap the benefits of exercise from the comfort of our couches? Before you start looking for clusterin vendors on the internet, it’s important to keep a few things in mind. First, it’s important to remember that these studies were performed in mice. The authors of the study did, however, begin to look at some of these pathways in exercised humans. They exposed one group of veterans with mild cognitive impairment to an exercise regimen and found that some of the changes in protein levels that they observed in mice were also present in humans, including increased levels of clusterin. Much more work is needed to further characterize gene expression and protein changes in humans after exercise and to link these changes to improved cognition. Another important point is that the true biological basis of the cognitive benefits of age and exercise is almost guaranteed to be more complicated than a single or even a handful of proteins circulating in the blood. Moreover, altering gene expression or proteins involved in these very crucial pathways can carry risks independent of their effects on memory. Therefore, highly controlled clinical trials must first conclude that these treatments are safe before even considering their efficacy. There are, however, ongoing clinical trials using plasma from young donors to treat neurodegenerative diseases like Alzheimer’s and Parkinson’s Disease5, giving us hope that one-day studies like these will lead to more informed and effective treatments for neurological diseases.

 

References

  1. Villeda SA, Plambeck KE, Middeldorp J, Castellano JM, Mosher KI, Luo J, et al. Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice. Nat Med. 20, 659-63 (2014).
  1. De Miguel Z, Khoury N, Betley MJ, Lehallier B, Willoughby D, Olsson N, Yang AC, et al. Exercise plasma boosts memory and dampens brain inflammation via clusterin. Nature. Epub ahead of print (2021). 
  1. Monje ML, Toda H, Palmer TD. Inflammatory blockade restores adult hippocampal neurogenesis. Science 302, 1760-5 (2003).
  1. Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH. Mechanisms underlying inflammation in neurodegeneration. Cell 140, 918-34 (2010).
  1. “Young Plasma.” Alzforum. https://www.alzforum.org/therapeutics/young-plasma 

Cover image by roxanawilliams1920 from Pixabay https://pixabay.com/photos/running-woman-fitness-runner-6252827/ 

 

 

 

IAES PNK Partnership logo 500x419 - Blood, Sweat, and Clusterin

Click here or the image below to subscribe to our mailing list:

subscribe - Halloween Ideas

Your generous Donations allow IAES to continue our important work and save lives!

guidestar platinum logo 300x300 1 e1605914935941 - Blood, Sweat, and Clusterin

 

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.   Trivia Playing cards 3 FB 500x419 - Blood, Sweat, and Clusterin 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.   AE Warrior Store 300x200 - Blood, Sweat, and Clusterin

Be a part of the solution by supporting IAES with a donation today.

why zebra - Aphasia as a Symptom of Autoimmune Encephalitis

Our website is not a substitute for independent professional medical advice. Nothing contained on our website is intended to be used as medical advice. No content is intended to be used to diagnose, treat, cure or prevent any disease, nor should it be used for therapeutic purposes or as a substitute for your own health professional's advice. Although THE INTERNATIONAL AUTOIMMUNE ENCEPHALITIS SOCIETY  provides a great deal of information about AUTOIMMUNE ENCEPHALITIS, all content is provided for informational purposes only. The International Autoimmune Encephalitis Society  cannot provide medical advice.


International Autoimmune Encephalitis Society is a charitable non-profit 501(c)(3) organization founded in 2016 by Tabitha Andrews Orth, Gene Desotell and Anji Hogan-Fesler. Tax ID# 81-3752344. Donations raised directly supports research, patients, families and caregivers impacted by autoimmune encephalitis and to educating healthcare communities around the world. Financial statement will be made available upon request.

CONTACT US


352-527-2470

IAES@AUTOIMMUNE-ENCEPHALITIS.ORG

Quick Link


Home


About Us


Contact Us


Donate


Privacy Policy


Translate »