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


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
—-—-
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
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:
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 –
We recruited 40 people with AE and 28 healthy volunteers who provided blood samples. These blood samples were evaluated in the laboratory for:
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.
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 –
———-
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:
On June 16 th, 2022, Tabitha Orth, President and Founder of International Autoimmune Encephalitis Society officially became the 7,315 th “point of light”. Recognized for the volunteer work she and IAES has done to spark change and improve the world for those touched by Autoimmune Encephalitis. The award was founded by President George H.W. Bush in 1990.
Become an Advocate by sharing your story. It may result in accurate diagnosis for someone suffering right now who is yet to be correctly identified. Submit your story with two photos to IAES@autoimmune-encephalitis.org
International Autoimmune Encephalitis Society (IAES), home of the AEWarrior®, is the only Family/Patient-centered organization that assists members from getting a diagnosis through to recovery and the many challenges experienced in their journey. Your donations are greatly appreciated and are the direct result of IAES’ ability to develop the first product in the world to address the needs of patients, Autoimmune Encephalitis Trivia Playing Cards. Every dollar raised allows us to raise awareness and personally help Patients, Families, and Caregivers through their Journey with AE to ensure that the best outcomes can be reached. Your contribution to our mission will help save lives and improve the quality of life for those impacted by AE.
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).
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
—-
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.
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
|
—-
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:
On June 16 th, 2022, Tabitha Orth, President and Founder of International Autoimmune Encephalitis Society officially became the 7,315 th “point of light”. Recognized for the volunteer work she and IAES has done to spark change and improve the world for those touched by Autoimmune Encephalitis. The award was founded by President George H.W. Bush in 1990.
Become an Advocate by sharing your story. It may result in accurate diagnosis for someone suffering right now who is yet to be correctly identified. Submit your story with two photos to IAES@autoimmune-encephalitis.org
International Autoimmune Encephalitis Society (IAES), home of the AEWarrior®, is the only Family/Patient-centered organization that assists members from getting a diagnosis through to recovery and the many challenges experienced in their journey. Your donations are greatly appreciated and are the direct result of IAES’ ability to develop the first product in the world to address the needs of patients, Autoimmune Encephalitis Trivia Playing Cards. Every dollar raised allows us to raise awareness and personally help Patients, Families, and Caregivers through their Journey with AE to ensure that the best outcomes can be reached. Your contribution to our mission will help save lives and improve the quality of life for those impacted by AE.
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
—-
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
■ 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).
■ 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.
■ 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:
On June 16 th, 2022, Tabitha Orth, President and Founder of International Autoimmune Encephalitis Society officially became the 7,315 th “point of light”. Recognized for the volunteer work she and IAES has done to spark change and improve the world for those touched by Autoimmune Encephalitis. The award was founded by President George H.W. Bush in 1990.
Become an Advocate by sharing your story. It may result in accurate diagnosis for someone suffering right now who is yet to be correctly identified. Submit your story with two photos to IAES@autoimmune-encephalitis.org
International Autoimmune Encephalitis Society (IAES), home of the AEWarrior®, is the only Family/Patient-centered organization that assists members from getting a diagnosis through to recovery and the many challenges experienced in their journey. Your donations are greatly appreciated and are the direct result of IAES’ ability to develop the first product in the world to address the needs of patients, Autoimmune Encephalitis Trivia Playing Cards. Every dollar raised allows us to raise awareness and personally help Patients, Families, and Caregivers through their Journey with AE to ensure that the best outcomes can be reached. Your contribution to our mission will help save lives and improve the quality of life for those impacted by AE.
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.
Recent Comments