Select Page
10 Big Unanswered Questions in Neuroscience Part 1

10 Big Unanswered Questions in Neuroscience Part 1


August 30, 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/

As AE Warriors, caregivers, friends, family, loved ones and medical personnel we have been unwittingly thrown into a world we may or may not have been at all curious about previously. No matter where we are in our individual AE journeys, neurology and neuroscience are terms we all know well. AE may have sent us on this journey deep into the amazing world of neurology, but we all have found out just how interesting and fascinating our brains can be! In the first of a two-part series, Sophie Liebergall has helped us to better understand 10 big unanswered questions in neuroscience! We hope you enjoy this and look forward to Part II.

——

Introduction

 

This past year, astrophysicists used NASA’s James Webb Space telescope to observe a star that is over 33 billion light years away from earth. Back on earth, particle physicists used the Large Hadron Collider in Switzerland to confirm the existence of incomprehensibly tiny subatomic particles. But despite these astounding scientific and technologic advances, we still have a lot to learn about what is going on in the organ inside our own skulls! In part one of what will be a two-part series, we discuss a few of the fundamental questions about the brain that have remained mysterious to neuroscientists.  

1. Where do our memories go when we put them in long-term storage?

For a brain to perform complex tasks, such as telling the body to execute a series of movements or being able to recognize and evade a predator, it must be able to recall information that was gathered during previous experiences. Neuroscience researchers divide memory storage into two stages: short-term memory and long-term memory.1 When the brain senses something in its environment, it can hold that information for a few seconds to minutes as a short-term memory.2 Over time, scientists have gathered clues that short-term memories (at least those of conscious facts and events) are stored in the hippocampus, an almond-size region nestled on either side below the brain’s surface on either side.3 But sometimes the brain needs to hold onto information for longer periods of time (up to a lifetime) so that is can be recalled later. We’re fairly certain that long-term memories aren’t stored in the hippocampus; but where exactly these long-term memories go remains a mystery. Several recent studies seem to suggest that, unlike short-term memories, long-term memories may be widely distributed in the cerebral cortex (the large surface of the brain that is used for complex thought), with different features of the memory spread across different regions.4,5 You can read more about the process of memory formation and how it can go wrong in some diseases here!

2. Why do we need to sleep?

Evolution has shaped the human body into an elegant and efficient machine, with a versatile digestive system, a continuously beating heart, and a thinking brain. However, one of our basic biologic functions, sleep, seems like something that should have been stamped out by evolution many generations ago. When we sleep, we are essentially unconscious for up to one-third of the day. For our ancestors, this is a time when they were particularly vulnerable to predators and unable to gather food. So why, then, has sleep survived the test of natural selection? 

Sleep is absolutely necessary for all animals (from armadillos, who sleep up to twenty hours each day, to giraffes who need just two hours of sleep a day).6 After just a couple days of total sleep deprivation, many people will start to show symptoms of psychosis.7 And if the sleep deprivation continues, it can even be deadly. In a study from the 1980s, which would likely be forbidden under contemporary ethical standards, researchers subjected a group of rats to total sleep deprivation. All of the rats died by the 32nd day of the study.8 The ultrarare genetic disease Fatal familial insomnia gives further insight into the danger of insomnia in humans. Patients with Fatal familial insomnia slowly lose their ability to fall and stay asleep.9 Tragically, these patients always die soon after they completely lose their ability to sleep.

Sleep is important for a variety of our body and brain’s normal functions: solidifying events that occurred during the day as long term memories,10 recalibrating the strength of the connections between brain cells,11,12 balancing the hormones that control our appetites and metabolism,13 and clearing the toxic byproducts of brain cell activity.14 But scientists still do not know what function (or functions) of sleep are the primary reason why it is essential for survival. Read more about the possible hypothesis for why we sleep in this PNK article!

3. Why do we dream?

Even more mysterious than the question of why we sleep is the question of why we dream. Though sleep has been a target of neuroscience research for decades, there are inherent challenges to studying dreaming that prevent us from using some of the traditional tools of neuroscience research. The study of dreams still largely relies on dream reports, when a person wakes up and verbally reports or writes down whether they were dreaming and what their dream was about. Dream reports are often unreliable because of the bias and imperfect memory of the dreamer. This can prevent researchers from making objective scientific conclusions from dream reports. Furthermore, all animals clearly display some form of sleep, but there is no conclusive evidence that other animals have dreams. This makes it challenging or even impossible to study dreaming using laboratory animals, which generally allow us to perform important experiments that would take too long or be too dangerous in humans.

Though we have recently developed more sophisticated tools that allow us to correlate the dream reports of humans with measures of brain activity, many of these studies have only raised more questions. It was once thought that dreaming only occurred during rapid eye movement (REM) sleep, the phase of sleep during which brain waves look most similar to the waking state. But more recent evidence suggests that dreams occur during both REM and non-REM sleep (though dreams that occur during REM sleep do seem to be more vivid than the dreams that occur during non-REM sleep).15,16

Another strange aspect of dreaming is called the dream-lag effect, which describes a phenomenon in which you’re most likely to dream about real life events that happened 5-7 days ago.17 And we still don’t have a clue as to why some people are prone to sleepwalking: a state in which individuals are clearly deep in a dream, but somehow are aware of their surroundings enough to navigate a space, consume food, or even drive a motor vehicle.18 You can learn more about the neuroscience of dreaming here!

4. How do the general anesthesia drugs used during surgery make you unconscious?

General anesthetics, the class of drugs which cause temporary unconsciousness, have made it possible for doctors to perform lifesaving and life-altering surgeries that would otherwise be impossibly painful for patients. General anesthetics are some of the most safe and reliable medications that are administered by doctors. But we still don’t have an understanding of where general anesthetics act in the brain, or of what their ultimate effects are on brain processes. Even though anesthetic drugs all have the same end effect of making a patient unconscious, anesthetics can come in all different shapes and sizes. Some, like xenon gas, have a structure as simple a single atom, whereas others, like alfaxalone, have a complex structure with many branches and rings.19,20  Some are inhaled as a gas, whereas others are injected into the bloodstream. And, strangely, general anesthetics don’t just sedate animals with complex brains like humans. They also impair the movement and environmental responsiveness of plants and even single-celled organisms!21 You can learn more about the possible mechanisms of general anesthetics and their relationship with sleep in this PNK article.

5. How does each area of the brain know what function it is supposed to perform?

In the mid-19th century, in the early days of modern neuroscience, the French physician Paul Broca learned of a patient with a unique neurologic condition. This patient had lost the ability to generate speech, but had somehow maintained the ability to comprehend speech.22 When this patient died, Broca performed an autopsy, where he discovered that the patient had sustained an injury to a very specific area of their frontal lobe. Broca’s work inspired other physicians of his age to look for injuries to specific areas of their brains in their patients with specific neurologic symptoms. If multiple patients with the same symptoms had an injury in the same region, then it could be assumed that an injury to that region was the cause of the symptom. These studies of localized brain injuries led neurologists to believe that different regions of the brain are responsible for the different functions of the brain. For example, one region of the brain is required for the ability to move a hand, whereas another region of the brain is required to read language.

Modern-day neuroscientists and neurologists take the idea that certain regions of the brain are responsible for certain functions for granted. But there is a great deal of complexity to this picture that we have yet to understand. The exact mapping of the functions of the brain can vary between individuals – sometimes in dramatic ways. For example, most people have the speech control area of their brain somewhere on the left side of their brain. But occasionally, in people who are left-handed, the speech control area is instead found on the right side.23 This variability between individuals suggests that the process of assigning a function to a specific brain region doesn’t follow a simple blueprint. But we still don’t know how the brain knows which functions it needs to perform. And we also don’t know each function is assigned to a particular region of the brain.

Stay tuned for part two with five more big unanswered questions in neuroscience coming this summer!

References

1.         Cowan, N. What are the differences between long-term, short-term, and working memory? Prog Brain Res 169, 323–338 (2008).

2.         Atkinson, R. C. & Shiffrin, R. M. Human Memory: A Proposed System and its Control Processes11This research was supported by the National Aeronautics and Space Administration, Grant No. NGR-05-020-036. The authors are indebted to W. K. Estes and G. H. Bower who provided many valuable suggestions and comments at various stages of the work. Special credit is due J. W. Brelsford who was instrumental in carrying out the research discussed in Section IV and whose overall contributions are too numerous to report in detail. We should also like to thank those co-workers who carried out a number of the experiments discussed in the latter half of the paper; rather than list them here, each will be acknowledged at the appropriate place. in Psychology of Learning and Motivation (eds. Spence, K. W. & Spence, J. T.) vol. 2 89–195 (Academic Press, 1968).

3.         Duff, M. C., Covington, N. V., Hilverman, C. & Cohen, N. J. Semantic Memory and the Hippocampus: Revisiting, Reaffirming, and Extending the Reach of Their Critical Relationship. Frontiers in Human Neuroscience 13, (2020).

4.         Yadav, N. et al. Prefrontal feature representations drive memory recall. Nature 608, 153–160 (2022).

5.         Roy, D. S. et al. Brain-wide mapping reveals that engrams for a single memory are distributed across multiple brain regions. Nat Commun 13, 1799 (2022).

6.         Campbell, S. S. & Tobler, I. Animal sleep: a review of sleep duration across phylogeny. Neurosci Biobehav Rev 8, 269–300 (1984).

7.         Waters, F., Chiu, V., Atkinson, A. & Blom, J. D. Severe Sleep Deprivation Causes Hallucinations and a Gradual Progression Toward Psychosis With Increasing Time Awake. Front Psychiatry 9, 303 (2018).

8.         Everson, C. A., Bergmann, B. M. & Rechtschaffen, A. Sleep deprivation in the rat: III. Total sleep deprivation. Sleep 12, 13–21 (1989).

9.         Fatal Familial Insomnia – Symptoms, Causes, Treatment | NORD. https://rarediseases.org/rare-diseases/fatal-familial-insomnia/.

10.      Diekelmann, S. & Born, J. The memory function of sleep. Nat Rev Neurosci 11, 114–126 (2010).

11.       Frank, M. G. Erasing Synapses in Sleep: Is It Time to Be SHY? Neural Plast 2012, 264378 (2012).

12.      Tononi, G. & Cirelli, C. Sleep function and synaptic homeostasis. Sleep Medicine Reviews 10, 49–62 (2006).

13.      Sharma, S. & Kavuru, M. Sleep and Metabolism: An Overview. Int J Endocrinol 2010, 270832 (2010).

14.      Xie, L. et al. Sleep Drives Metabolite Clearance from the Adult Brain. Science 342, 10.1126/science.1241224 (2013).

15.      Foulkes, W. D. Dream reports from different stages of sleep. J Abnorm Soc Psychol 65, 14–25 (1962).

16.      Hobson, J. A., Pace-Schott, E. F. & Stickgold, R. Dreaming and the brain: toward a cognitive neuroscience of conscious states. Behav Brain Sci 23, 793–842; discussion 904-1121 (2000).

17.      Eichenlaub, J. et al. The nature of delayed dream incorporation (‘dream‐lag effect’): Personally significant events persist, but not major daily activities or concerns. J Sleep Res 28, e12697 (2019).

18.      Cochen De Cock, V. Sleepwalking. Curr Treat Options Neurol 18, 6 (2016).

19.      PubChem. Alfaxalone. https://pubchem.ncbi.nlm.nih.gov/compound/104845.

20.      PubChem. Xenon. https://pubchem.ncbi.nlm.nih.gov/compound/23991.

21.      Kelz, M. B. & Mashour, G. A. The Biology of General Anesthesia from Paramecium to Primate. Current Biology 29, R1199–R1210 (2019).

22.      Dronkers, N. F., Plaisant, O., Iba-Zizen, M. T. & Cabanis, E. A. Paul Broca’s historic cases: high resolution MR imaging of the brains of Leborgne and Lelong. Brain 130, 1432–1441 (2007).

23.      Packheiser, J. et al. A large-scale estimate on the relationship between language and motor lateralization. Sci Rep 10, 13027 (2020).

Cover photo made with biorender.com.

IAES PNK Partnership logo 500x419 - 10 Big Unanswered Questions in Neuroscience Part 1

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 - 10 Big Unanswered Questions in Neuroscience Part 1

 

 

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 - 10 Big Unanswered Questions in Neuroscience Part 1

 

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 - 10 Big Unanswered Questions in Neuroscience Part 1 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 - 10 Big Unanswered Questions in Neuroscience Part 1

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

why zebra - Aphasia as a Symptom of Autoimmune Encephalitis
image - 10 Big Unanswered Questions in Neuroscience Part 1
A link between COVID-19 and autoimmune encephalitis?

A link between COVID-19 and autoimmune encephalitis?


August 23, 2023 | by Kara McGaughey, 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

The Covid 19 pandemic spread its insidious tentacles all over the world. Scientific papers, chapters of books and entire university courses can be counted on to outline and delve deep into the wide spread effects on all levels of society that Covid has caused. For the AE community we are not only affected by the general Covid effects but possibly, also, in relation to our own ongoing AE journeys. How does the Covid virus affect AE? Is there a link between Covid 19 and AE? Kara McGaughey from the PNK team has done a wonderful job helping us all better understand what can be understood about this possible relationship at this time and what it may mean for the future of AE research.

Coronavirus Disease (COVID-19) is an ongoing global health crisis with more than 760 million confirmed cases and nearly 7 million deaths reported by the World Health Organization as of June 2023.1 However, as we enter into the fourth year of the pandemic, we’re beginning to understand that knowing the number of active cases of COVID-19 isn’t the whole story.

In this post, we will dive into the long-term consequences of COVID-19, with a focus on the potential link between COVID-19 and autoimmune encephalitis (AE). We will explore why scientists think these diseases might be connected as well as what implications these new, post-COVID cases can have for AE research.

What is the connection between COVID-19 and AE?

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a newly-emerged virus that causes Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infection results in various systemic and respiratory symptoms such as fever, fatigue, cough, and difficulty breathing. In cases of severe disease, these symptoms can cause heart and lung failure, requiring hospitalization. However, the struggle isn’t always over once infection has subsided. Around 15% of patients have persistent symptoms for months after testing positive.2-3 These symptoms, often including fatigue and brain fog, can be debilitating. In many cases, a patient’s ability to carry out normal, everyday activities is profoundly affected. In a much, much smaller percentage of cases, the SARS-CoV-2 virus can also function as a trigger for some autoimmune diseases, like Guillain-Barré Syndrome (GBS), rheumatoid arthritis, and even autoimmune encephalitis (AE).4-5

AE refers to a group of conditions that occur when the body’s immune system mistakenly attacks healthy brain tissue.5 The cause of AE is often unknown. However, experts say that, in some cases, exposure to certain bacteria or viruses may increase someone’s risk of AE. For example, infection with herpes simplex virus 1 (HSV-1) has been linked to later development of AE, particularly the anti-NMDA AE subtype.7

We are seeing something similar happening now with SARS-CoV-2 viral infections (and re-infections) leading to an uptick in the number of AE diagnoses. Case reports of this so-called “post-COVID AE” have come from all over the world — Iran, Canada, France, Italy, the United Kingdom, China, Sweden, India, Mexico, and the United States — and describe patients across a wide range of ages from 2 to 88.4,8-9  A majority of these post-COVID AE diagnoses are for either limbic or anti-NMDA AE subtypes with patients experiencing headache, cognitive impairment, and seizures.4 Fortunately, a majority of patients respond well to treatment.4

How can SARS-CoV-2 infection lead to AE?

How exactly AE develops from SARS-CoV-2 infections is not yet fully understood. However, scientists do have some theories.

The “cytokine storm” and inflammatory cytokines:

Cytokines are small proteins that are crucial for controlling the immune system’s activity.10 Inflammatory cytokinesact as signals that tell the immune system to turn on, enabling the body to recognize and destroy foreign invaders (like the SARS-CoV-2 virus). Anti-inflammatory cytokines are responsible for dialing immune system activity back down once the threat has been neutralized. During the pandemic, you may have heard about COVID-19 causing the overproduction of inflammatory cytokines, known as a “cytokine storm.” With too many of these cytokines released in the body, immune system activity and inflammation can spiral out of control, leading to, in the worst cases, multi-organ failure.4-6,11

Scientists think that one link between COVID-19 and AE is a particular inflammatory cytokine, IL-6, released during this storm.5,12 Elevated levels of IL-6 are often found in patients with anti-NMDA AE.11,13-14 In fact, they are considered a characteristic feature of this AE subtype.13 Given that many post-COVID AE cases are anti-NMDA, it is possible that high levels of IL-6 as a result of SARS-CoV-2 viral infection could be one reason for the increased risk of developing AE after COVID-19.

Accidental autoimmunity:

While we want an immune system that can recognize and react to foreign invaders (e.g., SARS-CoV-2, tumor cells, etc.), it is just as important that our own cells don’t get caught up in the crossfire. Fortunately, our immune system has evolved to both quickly and accurately distinguish outsiders from the body itself. However, sometimes in the face of viral infections that cause extreme inflammation, this protective, self-recognition feature goes awry and the body begins to produce antibodies that accidentally target its own tissue (“autoantibodies”). This autoantibody-induced self destruction is called autoimmunity.4 It is possible that SARS-CoV-2 viral infections induce AE through an autoimmune process that generates antibodies targeting brain cells.

What implications might this have for AE research?

AE is notoriously rare and frequently misdiagnosed.15 Evidence for a link between SARS-CoV-2 infections and the development of AE means more of the scientific spotlight is being given to AE. This increased awareness could make physicians more likely to explore AE as a possible diagnosis, decreasing the time patients spend in limbo waiting for answers and treatment. Perhaps more importantly, in scientific research, money and resources flow where attention goes. This could mean more funding for AE research and more AE clinical trials. Hopefully, this will lead to a better understanding not only of the relationship between COVID-19 and AE, but AE and autoimmunity more broadly.

A final note: It’s important to remember that getting infected or re-infected with COVID-19 doesn’t mean you will end up with AE. While there have been a fair number of case reports of post-COVID AE, it is still a rare outcome. Moreover, it is very difficult to establish any sort of causal link between SARS-CoV-2 infection and the later development of a disease. In most cases it is impossible to know whether some of these patients would have developed AE even without exposure to COVID-19. Nonetheless, the best path forward is to be aware of ongoing research and continue preventive measures, like wearing a mask in high-risk situations and making sure you stay up to date on COVID-19 vaccinations.

Work cited:

  1. WHO Coronavirus (COVID-19) Dashboard. (n.d.). Retrieved May 1, 2023, from https://covid19.who.int
  2. Nearly One in Five American Adults Who Have Had COVID-19 Still Have “Long COVID.” (2022, June 22).https://www.cdc.gov/nchs/pressroom/nchs_press_releases/2022/20220622.htm
  3. Lledó, G. M., Sellares, J., Brotons, C., Sans, M., Antón, J. D., Blanco, J., Bassat, Q., Sarukhan, A., Miró, J. M., & de Sanjosé, S. (2022). Post-acute COVID-19 syndrome: A new tsunami requiring a universal case definition. Clinical Microbiology and Infection, 28(3), 315–318. https://doi.org/10.1016/j.cmi.2021.11.015
  4. Stoian, A., Stoian, M., Bajko, Z., Maier, S., Andone, S., Cioflinc, R. A., Motataianu, A., Barcutean, L., & Balasa, R. (2022). Autoimmune Encephalitis in COVID-19 Infection: Our Experience and Systematic Review of the Literature. Biomedicines, 10(4), 774. https://doi.org/10.3390/biomedicines10040774
  5. Nabizadeh, F., Balabandian, M., Sodeifian, F., Rezaei, N., Rostami, M. R., & Naser Moghadasi, A. (2022). Autoimmune encephalitis associated with COVID-19: A systematic review. Multiple Sclerosis and Related Disorders, 62, 103795.https://doi.org/10.1016/j.msard.2022.103795
  6. Payus, A. O., Jeffree, M. S., Ohn, M. H., Tan, H. J., Ibrahim, A., Chia, Y. K., & Raymond, A. A. (2022). Immune-mediated neurological syndrome in SARS-CoV-2 infection: A review of literature on autoimmune encephalitis in COVID-19. Neurological Sciences, 43(3), 1533–1547. https://doi.org/10.1007/s10072-021-05785-z
  7. Armangue, T., Spatola, M., Vlagea, A., Mattozzi, S., Cárceles-Cordon, M., Martinez-Heras, E., Llufriu, S., Muchart, J., Erro, M. E., Abraira, L., Moris, G., Monros-Giménez, L., Corral-Corral, Í., Montejo, C., Toledo, M., Bataller, L., Secondi, G., Ariño, H., Martínez-Hernández, E., … Zabalza, A. (2018). Frequency, symptoms, risk factors, and outcomes of autoimmune encephalitis after herpes simplex encephalitis: A prospective observational study and retrospective analysis. The Lancet Neurology, 17(9), 760–772. https://doi.org/10.1016/S1474-4422(18)30244-8
  8. Saffari, P., Aliakbar, R., Haritounian, A., Mughnetsyan, R., Do, C., Jacobs, J., Hoffer, J., Arieli, R., Liu, A. K., Saffari, P., Aliakbar, R., Haritounian, A., Mughnetsyan, R., Do, C., Jacobs, J., Hoffer, J., Arieli, R., & Liu, A. K. (2023). A Sharp Rise in Autoimmune Encephalitis in the COVID-19 Era: A Case Series. Cureus, 15(2). https://doi.org/10.7759/cureus.34658
  9. Mekheal, E., Mekheal, M., Roman, S., Mikhael, D., Mekheal, N., Manickam, R., Mekheal, E., Mekheal, M., Roman, S., Mikhael, D., Mekheal, N., & Manickam, R. (2022). A Case Report of Autoimmune Encephalitis: Could Post-COVID-19 Autoimmunity Become a Lethal Health Issue? Cureus, 14(6). https://doi.org/10.7759/cureus.25910
  10. Kim, E. Y., & Moudgil, K. D. (2008). Regulation of autoimmune inflammation by pro-inflammatory cytokines. Immunology Letters, 120(1), 1–5. https://doi.org/10.1016/j.imlet.2008.07.008
  11. Byun, J.-I., Lee, S.-T., Moon, J., Jung, K.-H., Sunwoo, J.-S., Lim, J.-A., Kim, T.-J., Shin, Y.-W., Lee, K.-J., Jun, J.-S., Lee, H. S., Lee, W.-J., Kim, Y.-S., Kim, S., Jeon, D., Park, K.-I., Jung, K.-Y., Kim, M., Chu, K., & Lee, S. K. (2016). Distinct intrathecal interleukin-17/interleukin-6 activation in anti-N-methyl-d-aspartate receptor encephalitis. Journal of Neuroimmunology, 297, 141–147. https://doi.org/10.1016/j.jneuroim.2016.05.023
  12. Liu, J., Li, S., Liu, J., Liang, B., Wang, X., Wang, H., Li, W., Tong, Q., Yi, J., Zhao, L., Xiong, L., Guo, C., Tian, J., Luo, J., Yao, J., Pang, R., Shen, H., Peng, C., Liu, T., … Zheng, X. (2020). Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. EBioMedicine, 55, 102763.https://doi.org/10.1016/j.ebiom.2020.102763
  13. Liu, J., Liu, L., Kang, W., Peng, G., Yu, D., Ma, Q., Li, Y., Zhao, Y., Li, L., Dai, F., & Wang, J. (2020). Cytokines/Chemokines: Potential Biomarkers for Non-paraneoplastic Anti-N-Methyl-D-Aspartate Receptor Encephalitis. Frontiers in Neurology, 11.https://www.frontiersin.org/articles/10.3389/fneur.2020.582296
  14. Byun, J.-I., Lee, S.-T., Moon, J., Jung, K.-H., Sunwoo, J.-S., Lim, J.-A., Kim, T.-J., Shin, Y.-W., Lee, K.-J., Jun, J.-S., Lee, H. S., Lee, W.-J., Kim, Y.-S., Kim, S., Jeon, D., Park, K.-I., Jung, K.-Y., Kim, M., Chu, K., & Lee, S. K. (2016). Distinct intrathecal interleukin-17/interleukin-6 activation in anti-N-methyl-d-aspartate receptor encephalitis. Journal of Neuroimmunology, 297, 141–147. https://doi.org/10.1016/j.jneuroim.2016.05.023
  15. Lancaster, E. (2016). The Diagnosis and Treatment of Autoimmune Encephalitis. Journal of Clinical Neurology (Seoul, Korea), 12(1), 1–13. https://doi.org/10.3988/jcn.2016.12.1.1

 

IAES PNK Partnership logo 500x419 - A link between COVID-19 and 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 - A link between COVID-19 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 - A link between COVID-19 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 - A link between COVID-19 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 - A link between COVID-19 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
image - A link between COVID-19 and autoimmune encephalitis?
Who do you become when you are sleepy?

Who do you become when you are sleepy?


July 12, 2023 | by
 Lindsay Ejoh, 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/

For all of us with AE, sleep can be an ongoing issue whether it be too little, too much, interrupted sleep cycles and everything in-between! Sleep issues often go hand in hand with an AE diagnosis. PNK author Lindsay Ejoh wrote this piece for the PNK weekly series and graciously gave IAES permission to publish it in our monthly series. We hope you find this as informative as we have!

——-

Introduction

Sleep experts recommend that most adults get 7-9 hours of good-quality sleep each day1,2 to avoid the myriad of issues that can occur when the brain and body are sleep-deprived. We all know what it is like to be tired. We may feel cranky and sluggish, as well as physically and mentally exhausted. We may also face issues with memory and attention3, emotional regulation, and diminished sex drive4,11. It is hard to feel like yourself when sleep-deprived- so what occurs in the brain during sleep deprivation, and how does it affect our daily lives?

Memory

As a child, I remember learning to trick my mother, a sleep-deprived emergency room nurse that worked the night shift, by asking her for permission to do things while she was coming home from work in the mornings, half-asleep. When I’d approach her in bed to ask for permission to go on a sleepover across town or to eat food we were saving for an occasion, she would always say yes. Eventually, she caught on, and warned me against waiting until she was sleepy to get my way, but the reason it worked at first is because sleep deprivation impacts decision-making5.

It also affects short-term memory, so as a result, my mother would never remember giving her approval. Long-term memory is affected as well, as sleep is very important for consolidation, or storage of memories. This is also why you may not remember everything you studied after cramming for an exam all night.

Reaction time

Being awake is not the same thing as being alert. When we are sleepy, we tend to have slow reaction times, or time to respond to a change in our environment. This can have devastating effects for those who operate cars and other heavy machinery while sleepy and can be dangerous for people who work with under these conditions. Sleep deprivation can make you 70% more likely to get into work-place accidents, which happen at higher rates in people with insomnia6. Additionally, missing just a couple hours of sleep can substantially increase the risk of having a car accident7. It may seem in the moment like you can stay awake while driving, but as explained in a previous NeuroKnow article, going 24 hours without sleep can be just as dangerous as driving drunk.

Changes in the brain

Sleep deprivation impacts many regions of your brain, but two are of notable importance: amygdala and prefrontal cortex.

Amygdala

Scientists can measure brain activity by taking functional magnetic resonance imaging (fMRI) scans. Using this method, researchers found that sleep deprivation leads to a hyperactive amygdala3. The amygdala is critical for emotional regulation, and its dysfunction may be related mood issues that occur from sleep deprivation. A single sleepless night can trigger a 30% increase in anxiety levels9, due to the loss of ability to regulate emotions or deal with stress, and people with anxiety disorders also have hyperactive amygdalae when faced with unpleasant changes in their environment10. In other words, sleep deprivation causes disruption in emotional centers in the brain, which is linked to increased anxiety.

Prefrontal Cortex

Another brain region with altered activity during sleep deprivation is the prefrontal cortex, which is important for rational thinking and decision-making3.  This region has decreased activity during sleep deprivation, and these activity patterns are associated with impaired judgment, a common symptom of sleep deprivation.  

Chronic sleep deprivation and sleep apnea

Most of us have experienced sleep-deprivation in our lives, but for some, it is the norm. People who suffer from inadequate sleep for a prolonged period of time (weeks to years) are in a state of chronic sleep deprivation6. Many people wake up in the mornings feeling symptoms of sleep deprivation despite getting a long night of sleep, which may be indicative of a sleep disorder known as sleep apnea. Patients with sleep apnea wake up over a hundred times throughout the night, due to difficulty breathing12. A research lab in Australia found that sleep apnea patients have altered brain activity during wakefulness13. Certain parts of their brains “go offline” briefly, despite being awake, and brain activity resembles that of a sleeping person14. Sleep disorder patients aren’t the only ones that experience this- it can occur from other forms of sleep deprivation. When sleep intrudes into the waking brain, this can lead to errors in tasks like driving. Despite being abnormal for humans, this brain activity phenomenon is not uncommon in the animal kingdom. Some animals like seals and dolphins sleep with half of their brains “awake” while the other halves are “asleep.”

Conclusion

Neuroscientists are working to understand the neurobiological consequences of sleep deprivation, so that we can inform and treat people who must continue to perform daily tasks despite running on little sleep. Though harmful for the brain, sleep deprivation is a normal part of daily life for 30-40% of US adults15, including parents of newborns, procrastinating college students, night-shift workers, military and medical personnel, sleep disorder patients, and many others. We live in a sleep-deprived society, where people are often celebrated for trading rest for productivity. I encourage you to take this as your sign to go to bed early tonight- you are not yourself when you’re sleepy!

References

  1. Watson NF, Badr MS, Belenky G, et al. Recommended amount of sleep for a healthy adult: a joint consensus statement of the American Academy of Sleep Medicine and Sleep Research Society. Sleep. 2015;38(6):843–844.
  2. Consensus Conference Panel, Watson, N. F., Badr, M. S., Belenky, G., Bliwise, D. L., Buxton, O. M., Buysse, D., Dinges, D. F., Gangwisch, J., Grandner, M. A., Kushida, C., Malhotra, R. K., Martin, J. L., Patel, S. R., Quan, S. F., Tasali, E., Non-Participating Observers, Twery, M., Croft, J. B., Maher, E., … Heald, J. L. (2015). Recommended Amount of Sleep for a Healthy Adult: A Joint Consensus Statement of the American Academy of Sleep Medicine and Sleep Research Society. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 11(6), 591–592. https://doi.org/10.5664/jcsm.4758
  3. Krause, A. J., Simon, E. B., Mander, B. A., Greer, S. M., Saletin, J. M., Goldstein-Piekarski, A. N., & Walker, M. P. (2017). The sleep-deprived human brain. Nature reviews. Neuroscience, 18(7), 404–418. https://doi.org/10.1038/nrn.2017.55
  4. Chen, K. F., Liang, S. J., Lin, C. L., Liao, W. C., & Kao, C. H. (2016). Sleep disorders increase risk of subsequent erectile dysfunction in individuals without sleep apnea: a nationwide population-base cohort study. Sleep medicine, 17, 64–68. https://doi.org/10.1016/j.sleep.2015.05.018
  5. Rasch, B., & Born, J. (2013). About sleep’s role in memory. Physiological reviews, 93(2), 681–766. https://doi.org/10.1152/physrev.00032.2012
  6. Suni, E. (2023, April 5). The relationship between sleep and workplace accidents. Sleep Foundation. Retrieved April 26, 2023, from https://www.sleepfoundation.org/excessive-sleepiness/workplace-accidents#references-197012
  7. AAA. (2016, December 6). Missing 1-2 hours of sleep doubles crash risk: Study reveals the dangers of getting less than 7 hours of sleep. ScienceDaily. Retrieved April 26, 2023 from www.sciencedaily.com/releases/2016/12/161206110235.htm
  8. Wong, M. M., Robertson, G. C., & Dyson, R. B. (2015). Prospective relationship between poor sleep and substance-related problems in a national sample of adolescents. Alcoholism, clinical and experimental research, 39(2), 355–362. https://doi.org/10.1111/acer.12618
  9. Ben Simon, E., Rossi, A., Harvey, A. G., & Walker, M. P. (2020). Overanxious and underslept. Nature human behaviour, 4(1), 100–110. https://doi.org/10.1038/s41562-019-0754-8
  10. Etkin, A., & Wager, T. D. (2007). Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. The American journal of psychiatry, 164(10), 1476–1488. https://doi.org/10.1176/appi.ajp.2007.07030504
  11. Sleep Center of Middle Tennessee. (2022, June 22). Sleep deprivation and its effects on the brain. Sleep Centers of Middle Tennessee. Retrieved April 26, 2023, from https://sleepcenterinfo.com/blog/sleep-deprivation-effects-on-brain/
  12. Slowik, J. M., Sankari, A., & Collen, J. F. (2022). Obstructive Sleep Apnea. In StatPearls. StatPearls Publishing.
  13. Hung, C. S., Sarasso, S., Ferrarelli, F., Riedner, B., Ghilardi, M. F., Cirelli, C., & Tononi, G. (2013). Local experience-dependent changes in the wake EEG after prolonged wakefulness. Sleep, 36(1), 59–72. https://doi.org/10.5665/sleep.2302
  14. Mannix, L. (2019, January 27). Your brain could be sleeping … even while you’re awake. The Sydney Morning Herald. Retrieved April 26, 2023, from https://www.smh.com.au/national/your-brain-could-be-sleeping-even-while-you-re-awake-20190124-p50tgg.html
  15. Centers for Disease Control and Prevention. (2022, November 2). Adults – sleep and sleep disorders. Centers for Disease Control and Prevention. Retrieved April 26, 2023, from https://www.cdc.gov/sleep/data-and-statistics/adults.html

Cover image by Karollyne Videira Hubert on Unsplash

References

  1. Zeng, J. & James, L. C. Intracellular antibody immunity and its applications. PLOS Pathog. 16, e1008657 (2020).
  2. CDC. COVID-19 and Your Health. Centers for Disease Control and Preventionhttps://www.cdc.gov/coronavirus/2019-ncov/your-health/about-covid-19/antibodies.html (2020).
  3. Elkon, K. & Casali, P. Nature and functions of autoantibodies. Nat. Clin. Pract. Rheumatol. 4, 491–498 (2008).
  4. Hermetter, C., Fazekas, F. & Hochmeister, S. Systematic Review: Syndromes, Early Diagnosis, and Treatment in Autoimmune Encephalitis. Front. Neurol. 9, 706 (2018).
  5. Graus, F. et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 15, 391–404 (2016).
  6. Anti-NMDA receptor encephalitis. Autoimmune Encephalitis Alliance https://aealliance.org/ae-types/anti-nmda-receptor-encephalitis/.
  7. Anti-AMPAR encephalitis. Autoimmune Encephalitis Alliance https://aealliance.org/ae-types/anti-ampar-encephalitis/.
  8. Anti-GABAA receptor encephalitis. Autoimmune Encephalitis Alliance https://aealliance.org/ae-types/anti-gabaa-receptor-encephalitis/.
  9. Anti-GABAB receptor encephalitis. Autoimmune Encephalitis Alliance https://aealliance.org/ae-types/anti-gabab-receptor-encephalitis/.
  10. LGI1-antibody encephalitis. Autoimmune Encephalitis Alliance https://aealliance.org/ae-types/lgi1-antibody-encephalitis/.
  11. CASPR2-antibody encephalitis. Autoimmune Encephalitis Alliance https://aealliance.org/ae-types/caspr2-antibody-encephalitis/.
  12. Malter, M. P., Helmstaedter, C., Urbach, H., Vincent, A. & Bien, C. G. Antibodies to glutamic acid decarboxylase define a form of limbic encephalitis. Ann. Neurol. 67, 470–478 (2010).
  13. Voltz, R. & Eichen, J. A Serologic Marker of Paraneoplastic Limbic and Brain-Stem Encephalitis in Patients with Testicular Cancer. N. Engl. J. Med. (1999).
  14. Graus, F. & Dalmau, J. Paraneoplastic neurological syndromes in the era of immune-checkpoint inhibitors. Nat. Rev. Clin. Oncol. 16, 535–548 (2019).
  15. Lancaster, E. Encephalitis and antibodies to synaptic and neuronal cell surface proteins. (2011).

 

IAES PNK Partnership logo 500x419 - Who do you become when you are sleepy?

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 - Who do you become when you are sleepy?

 

 

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 - Who do you become when you are sleepy?

 

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 - Who do you become when you are sleepy? 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 - Who do you become when you are sleepy?

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

why zebra - Aphasia as a Symptom of Autoimmune Encephalitis
image - Who do you become when you are sleepy?
What are intracellular and extracellular antibodies and what do the differences mean for patients with autoimmune encephalitis?

What are intracellular and extracellular antibodies and what do the differences mean for patients with autoimmune encephalitis?


June 14, 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/

——-

Introduction

There are many subtypes of autoimmune encephalitis (AE) that vary in their causes, the symptoms that patients experience, and what treatments are most effective. One of several factors that distinguish these different subtypes of AE is whether they involve intracellular or extracellular antibodies. In this post we will explore exactly what these terms mean and how they contribute to the differences between types of AE.

cell surface intracellular for website dalmau - What are intracellular and extracellular antibodies and what do the differences mean for patients with autoimmune encephalitis?

N Engl J Med 2018;378:840-51. DOI: 10.1056/NEJMra1708712 Copyright © 2018 Massachusetts Medical Society

What are intracellular and extracellular antibodies?

When a virus or bacteria enters our body, our immune system mounts an attack to destroy the foreign invader and protect us from harm. If our immune system is like an army ready for battle, then antibodies are like the scouts sent ahead of the battalion, patrolling for signs of a threat. Just like security personnel might scan ID badges to determine who is allowed in a building, each antibody is tasked with looking for a particular feature of something that the body has deemed harmful, called an antigen1. You might have heard antibodies discussed in reference to COVID-19, where infection with COVID-19 or vaccination can cause your body to produce antibodies that recognize features of the COVID-19 virus2. When antibodies are already present in the body, they can recognize the newly-arrived COVID-19 virus and mount an attack more quickly, helping to avoid a more serious infection.

This ability to quickly mount a defense against a threat before getting too sick is what makes antibodies an important part of our body’s immune system army. However, antibodies are only helpful if they recognize and defend against foreign substances that are harmful. Unfortunately, this isn’t the case in AE. Patients with AE have antibodies that bind to proteins found in their own cells, called autoantibodies (the prefix “auto” means self, so autoantibodies are antibodies that bind the body’s own proteins)3. Autoantibodies trigger the body’s immune system to attack itself, leading to the many symptoms of AE.

Each antibody can recognize only a small part of a whole cell, and there are many different parts of a cell that an antibody can recognize. What distinguishes extracellular from intracellular antibodies is whether their antigen (the ID badge they’re looking for) is inside or outside of the cell1,4. Extracellular antibodies recognize antigens that are on the outer surface of the cell (“extra” meaning outside). Conversely, intracellular antibodies recognize antigens that are inside the cell (“intra” meaning inside). The intracellular antibodies inside the cell trigger a different set of immune reactions than the extracellular antibodies outside of the cell.

Which kinds of AE involve intracellular versus extracellular antibodies?

Subtypes of AE are distinguished by what kind of autoantibody a patient has4, which is why they are typically named after the antigen that the autoantibody recognizes. For example, patients with anti-NMDAR AE have antibodies that recognize NMDA receptors. Types of AE associated with antigens outside the cell involve extracellular antibodies and types of AE associated with antigens inside the cell involve intracellular antibodies.

Many of the most common subtypes of AE involve extracellular antibodies4,5. Most are associated with antibodies that recognize a kind of protein that sits on the surface of the cell called a receptor. Receptors recognize and bind specific molecules and send signals that tell the cell how to respond. The receptors on neurons, a type of brain cell, are especially important because one neuron communicates with another by releasing molecules that can be recognized by the other neuron’s receptors. When antibodies bind the receptors, they activate an immune response and disrupt the ability of those receptors to participate in neural signaling. This leads to the many neurological symptoms of AE. Subtypes with these kinds of antibodies include anti-NMDAR AE6, anti-AMPAR AE7, anti-mGLUR5 antibody encephalitis4,5, GlyR antibody encephalitis4, anti-GABAa AE8, and anti-GABAb AE9. Several other extracellular antibodies associated with AE have antigens that sit on the cell’s surface and help with neuronal signaling but aren’t receptors themselves. Subtypes of AE with these kinds of antibodies include LGI1-antibody encephalitis10, CASPR2-antibody encephalitis11, and DPPX-antibody encephalitis4,5.

Subtypes of AE associated with intracellular antibodies are less common4,5. One example is GAD-antibody encephalitis12. Patients with this form of AE have antibodies that target Glutamic Acid Decarboxylase (GAD), a protein found inside the cell that is needed to synthesize GABA, a special type of molecule that is necessary for some kinds of neural signaling. Other subtypes of AE that target intracellular proteins are anti-Hu encephalitis5, and Ma2-antibody encephalitis13.

How are subtypes of AE associated with intracellular antibodies different from subtypes of AE associated with extracellular antibodies?

One big distinction is that most subtypes of AE associated with intracellular antibodies are also associated with tumors4. These subtypes of AE are called paraneoplastic. Paraneoplastic AE can occur when tumor cells express proteins on their surface that are normally expressed elsewhere. Sometimes this includes proteins that are normally found inside healthy neurons. To recognize and fight the tumor, the body’s immune system creates antibodies that recognize these proteins. These antibodies don’t distinguish the proteins found in the tumor cells from the healthy proteins found in neurons, so when they reach the brain, they also bind the naturally-occurring proteins in neurons and trigger the immune response responsible for the symptoms of AE14.

Patients with subtypes of AE associated with intracellular antibodies also tend to have poorer outcomes and respond worse to immunotherapy than patients with subtypes associated with extracellular antibodies4,15. This is because many of the symptoms of AE associated with extracellular antibodies are thought to result from the antibodies disrupting the normal function of the cell-surface proteins that they target. Conversely, the presence of intracellular autoantibodies typically accompanies an immune response against neurons more broadly that results in neuronal death. This means that successful treatment can often reverse symptoms of AE resulting from extracellular antibodies, as limiting the action of the antibodies allows the neurons to function normally, whereas even after treatment, symptoms do not typically reverse in subtypes of AE associated with intracellular antibodies, as many neurons have already died. For patients with paraneoplastic AE, removing the tumor is also an important step toward relieving symptoms15.

Despite general differences in outcomes for subtypes of AE associated with extracellular and intracellular antibodies, early detection and treatment are key to successful outcomes for all subtypes of AE4. Determining which type of AE a patient has can have an important impact on how doctors choose to treat and manage the disease. This distinction is also important for researchers developing new treatments and possible cures, as approaches that might work for one type of AE may not work for others. Determining which patients will be most receptive to a particular new treatment leads to better outcomes for clinical trials, which means more treatment options for all patients.

References

  1. Zeng, J. & James, L. C. Intracellular antibody immunity and its applications. PLOS Pathog. 16, e1008657 (2020).
  2. CDC. COVID-19 and Your Health. Centers for Disease Control and Preventionhttps://www.cdc.gov/coronavirus/2019-ncov/your-health/about-covid-19/antibodies.html (2020).
  3. Elkon, K. & Casali, P. Nature and functions of autoantibodies. Nat. Clin. Pract. Rheumatol. 4, 491–498 (2008).
  4. Hermetter, C., Fazekas, F. & Hochmeister, S. Systematic Review: Syndromes, Early Diagnosis, and Treatment in Autoimmune Encephalitis. Front. Neurol. 9, 706 (2018).
  5. Graus, F. et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 15, 391–404 (2016).
  6. Anti-NMDA receptor encephalitis. Autoimmune Encephalitis Alliance https://aealliance.org/ae-types/anti-nmda-receptor-encephalitis/.
  7. Anti-AMPAR encephalitis. Autoimmune Encephalitis Alliance https://aealliance.org/ae-types/anti-ampar-encephalitis/.
  8. Anti-GABAA receptor encephalitis. Autoimmune Encephalitis Alliance https://aealliance.org/ae-types/anti-gabaa-receptor-encephalitis/.
  9. Anti-GABAB receptor encephalitis. Autoimmune Encephalitis Alliance https://aealliance.org/ae-types/anti-gabab-receptor-encephalitis/.
  10. LGI1-antibody encephalitis. Autoimmune Encephalitis Alliance https://aealliance.org/ae-types/lgi1-antibody-encephalitis/.
  11. CASPR2-antibody encephalitis. Autoimmune Encephalitis Alliance https://aealliance.org/ae-types/caspr2-antibody-encephalitis/.
  12. Malter, M. P., Helmstaedter, C., Urbach, H., Vincent, A. & Bien, C. G. Antibodies to glutamic acid decarboxylase define a form of limbic encephalitis. Ann. Neurol. 67, 470–478 (2010).
  13. Voltz, R. & Eichen, J. A Serologic Marker of Paraneoplastic Limbic and Brain-Stem Encephalitis in Patients with Testicular Cancer. N. Engl. J. Med. (1999).
  14. Graus, F. & Dalmau, J. Paraneoplastic neurological syndromes in the era of immune-checkpoint inhibitors. Nat. Rev. Clin. Oncol. 16, 535–548 (2019).
  15. Lancaster, E. Encephalitis and antibodies to synaptic and neuronal cell surface proteins. (2011).

 

IAES PNK Partnership logo 500x419 - What are intracellular and extracellular antibodies and what do the differences mean for patients with 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 intracellular and extracellular antibodies and what do the differences mean 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 - What are intracellular and extracellular antibodies and what do the differences mean 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 - What are intracellular and extracellular antibodies and what do the differences mean 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 - What are intracellular and extracellular antibodies and what do the differences mean 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
image - What are intracellular and extracellular antibodies and what do the differences mean for patients with 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.

Translate »