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Peripheral monocytes and soluble biomarkers in autoimmune encephalitis

Peripheral monocytes and soluble biomarkers in autoimmune encephalitis

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:

 

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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.

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Peripheral monocytes and soluble biomarkers in autoimmune encephalitis

Psychiatric Manifestations of Autoimmune Encephalitis


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:

 

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
Rare and Seronegative Autoimmune Encephalitis

Rare and Seronegative Autoimmune Encephalitis

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:

 

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

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:

 

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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.

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Become an Advocate by sharing your story. It may result in accurate diagnosis for someone suffering right now who is yet to be correctly identified. Submit your story with two photos to IAES@autoimmune-encephalitis.org  

 

 

International Autoimmune Encephalitis Society (IAES), home of the AEWarrior®, is the only Family/Patient-centered organization that assists members from getting a diagnosis through to recovery and the many challenges experienced in their journey. Your donations are greatly appreciated and are the direct result of IAES’ ability to develop the first product in the world to address the needs of patients, Autoimmune Encephalitis Trivia Playing Cards. Every dollar raised allows us to raise awareness and personally help Patients, Families, and Caregivers through their Journey with AE to ensure that the best outcomes can be reached. Your contribution to our mission will help save lives and improve the quality of life for those impacted by AE.   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

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Rare and Seronegative Autoimmune Encephalitis

Cognition in autoimmune encephalitis


August 31, 2022 | Written by Sarah Griffith. 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

 —-

Cognition in Autoimmune Encephalitis – Summary

Source – Griffith, S., Wesselingh, R., Broadley, J., O’Shea, M., Kyndt, C., Meade, C., Long, B., Seneviratne, U., Reidy, N., Bourke, R., Buzzard, K., D’Souza, W., Macdonell, R., Brodtmann, A., Butzkueven, H., O’Brien, T. J., Alpitsis, R., Malpas, C. B., Monif, M., & Australian Autoimmune Encephalitis Consortium (2022). Psychometric deficits in autoimmune encephalitis: A retrospective study from the Australian Autoimmune Encephalitis Consortium. European journal of neurology, 10.1111/ene.15367. Advance online publication. https://doi.org/10.1111/ene.15367

 —-

Background

Autoimmune Encephalitis is a rare disease that affects different regions of the brain. Patients with this condition can have a variety of cognitive symptoms (for example, memory deficits, slow speed of information processing, attention lapses, word finding difficulties, trouble with following complex commands, difficulties in judgement, difficulties in comprehension of complex tasks, difficulties in forming new memories, and difficulties in understanding tasks or situations). These symptoms can change from one individual to another individual, and can fluctuate over the course of the illness. Also different types of autoimmune encephalitis can have differing presentation of the above symptoms.

Historically (and to this day) clinicians and researchers have used a scale called the modified Rankin Score as a tool to monitor an individual’s function – i.e. how independently they can function in their day to day life. However, this scale is very inaccurate and it does not capture complex and specific issues that might be troublesome for the patient. The modified Rankin Scale also does not reflect the gravity of the individual’s symptoms and does not provide in detail information about specific symptoms and complaints that the individual with autoimmune encephalitis might be experiencing. Importantly, the scale does not measure behavioural, mood or cognitive outcomes in autoimmune encephalitis. Cognitive changes can be associated with long term disease related morbidity and can reduce quality of life. Therefore we set out to gain a better understanding of the cognitive difficulties in autoimmune encephalitis.

 What did the researchers do?

We gathered cognitive data from patients previously diagnosed with autoimmune encephalitis (retrospective data) from six hospitals in Victoria (Australia) to inform the analysis. Patients were identified retrospectively through medical records with a search for diagnosis of autoimmune encephalitis with a hospital admission between July 2008 and July 2019. Patients who met this criteria participated in a neuropsychology assessment of their cognitive function (i.e., memory, attention, language, judgement, planning, comprehension, and recall. We collected clinical data about each patient and also information of various clinical investigations (i.e. lumbar puncture results and MRI).

 

What did the researchers find?

The average age of patients at diagnosis was 49 years old and more than half showing as seropositive autoimmune encephalitis (meaning they had identifiable antibodies in their blood or their cerebrospinal fluid). Of the seropositive group:

  • nine patients had anti-NMDAR antibodies,
  • nine anti-Leucine-rich glioma-inactivated 1 antibodies (LGI-1),
  • seven Voltage-gated potassium channel complex antibodies (unspecified) (VGKC),
  • three glutamic acid decarboxylase 65- (GAD65) one α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antibodies (AMPA),
  • one γ-aminobutyric acid B antibodies (GABA-Band), and
  • one collapsin response mediator protein 5 antibodies (CRMP5).

Forty two percent of patients had impairments on executive function tests (e.g. a set of tasks that includes working memory, planning, flexible thinking, and ability to remember multiple instructions, and capacity for self-regulation and ordering or prioritizing of tasks). The next most common impairment was on memory tests (e.g. the mental processes involved in acquiring, retaining and recalling information; 40.7% of patients).

For the first-time, we found 29 patterns of cognition among patients with autoimmune encephalitis in our analysis. The four most common patterns of cognition were:

  • Intact cognition (no cognitive deficits elicited),
  • Isolated memory deficits,
  • Executive dysfunction with memory impairment (combination pattern), and
  • Isolated visuospatial/visuoconstructional impairments (referring to visual or spatial perception of objects.

But, given we found 29 patterns means that cognitive outcomes in patients with autoimmune encephalitis are complex and need further detailed investigation.

What do these findings mean?

Our research highlighted that more detailed and systematic analysis of memory and executive function profiles in patients with autoimmune encephalitis is required. Impairments in memory and executive dysfunction can have huge implications for the patient and their caregivers, and tools that would better characterise and follow these symptoms in autoimmune encephalitis are needed. Understanding memory and executive function impairment in autoimmune encephalitis can help us in devising strategies that would assist patients with day to day function, but also monitor disease trajectory over time and delineate patient’s response to treatment. 

We could not predict good cognitive outcome (e.g. having ‘intact’ cognition after autoimmune encephalitis) in patients. We recommend clinicians provide ongoing comprehensive cognitive monitoring in patients with autoimmune encephalitis, and reactive intervention when required. An individualised approach will assist in the management the long-term morbidity of this disease, to minimise the effect on the individual’s quality of life and any damaging psychological outcomes.

 

 —-

To download a plain language PDF of the paper summarized in this blog, click the button below:

 

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Tabitha Orth 300x218 - Cognition 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.

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Become an Advocate by sharing your story. It may result in accurate diagnosis for someone suffering right now who is yet to be correctly identified. Submit your story with two photos to IAES@autoimmune-encephalitis.org  

 

 

International Autoimmune Encephalitis Society (IAES), home of the AEWarrior®, is the only Family/Patient-centered organization that assists members from getting a diagnosis through to recovery and the many challenges experienced in their journey. Your donations are greatly appreciated and are the direct result of IAES’ ability to develop the first product in the world to address the needs of patients, Autoimmune Encephalitis Trivia Playing Cards. Every dollar raised allows us to raise awareness and personally help Patients, Families, and Caregivers through their Journey with AE to ensure that the best outcomes can be reached. Your contribution to our mission will help save lives and improve the quality of life for those impacted by AE.   Trivia Playing cards 3 FB 500x419 - Cognition 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 - Cognition in autoimmune encephalitis

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

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Rare and Seronegative Autoimmune Encephalitis

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


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:

 

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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.

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Rare and Seronegative Autoimmune Encephalitis

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

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:

 

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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.

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


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

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