Psychiatric Manifestations of Autoimmune Encephalitis

by Alanna | Jan 24, 2023 | Australian Autoimmune Encephalitis Consortium

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

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

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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.

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

Download Plain Language Summary

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

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

On June 16 th, 2022, Tabitha Orth, President and Founder of International Autoimmune Encephalitis Society officially became the 7,315 th “point of light”. Recognized for the volunteer work she and IAES has done to spark change and improve the world for those touched by Autoimmune Encephalitis. The award was founded by President George H.W. Bush in 1990.

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

International Autoimmune Encephalitis Society (IAES), home of the AEWarrior®, is the only Family/Patient-centered organization that assists members from getting a diagnosis through to recovery and the many challenges experienced in their journey. Your donations are greatly appreciated and are the direct result of IAES’ ability to develop the first product in the world to address the needs of patients, Autoimmune Encephalitis Trivia Playing Cards. Every dollar raised allows us to raise awareness and personally help Patients, Families, and Caregivers through their Journey with AE to ensure that the best outcomes can be reached. Your contribution to our mission will help save lives and improve the quality of life for those impacted by AE. For this interested in face masks, clothing, mugs, and other merchandise, check out our AE Warrior Store! This online shop was born out of the desire for the AE patient to express their personal pride in fighting such a traumatic disease and the natural desire to spread awareness. Join our AE family and help us continue our mission to support patients, families and caregivers while they walk this difficult journey.

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

by Alanna | Oct 27, 2022 | Australian Autoimmune Encephalitis Consortium

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

A message from IAES Blog Staff:

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

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

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

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

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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.

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

Download Plain Language Summary

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

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

On June 16 th, 2022, Tabitha Orth, President and Founder of International Autoimmune Encephalitis Society officially became the 7,315 th “point of light”. Recognized for the volunteer work she and IAES has done to spark change and improve the world for those touched by Autoimmune Encephalitis. The award was founded by President George H.W. Bush in 1990.

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

International Autoimmune Encephalitis Society (IAES), home of the AEWarrior®, is the only Family/Patient-centered organization that assists members from getting a diagnosis through to recovery and the many challenges experienced in their journey. Your donations are greatly appreciated and are the direct result of IAES’ ability to develop the first product in the world to address the needs of patients, Autoimmune Encephalitis Trivia Playing Cards. Every dollar raised allows us to raise awareness and personally help Patients, Families, and Caregivers through their Journey with AE to ensure that the best outcomes can be reached. Your contribution to our mission will help save lives and improve the quality of life for those impacted by AE. For this interested in face masks, clothing, mugs, and other merchandise, check out our AE Warrior Store! This online shop was born out of the desire for the AE patient to express their personal pride in fighting such a traumatic disease and the natural desire to spread awareness. Join our AE family and help us continue our mission to support patients, families and caregivers while they walk this difficult journey.

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

Epilepsy and Autoimmune Encephalitis

by Alanna | Oct 11, 2022 | Australian Autoimmune Encephalitis Consortium

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

A message from IAES Blog Staff:

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

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

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

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

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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

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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 –

How common is drug-resistant epilepsy after autoimmune encephalitis?
What are the risk factors for the development of drug-resistant epilepsy after autoimmune encephalitis?
In the early part the disease, can the use of EEG tell us about a person’s likelihood of developing drug-resistant epilepsy?
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 –

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

Address risk factors such as status epilepticus with the goal to try and reduce the long-term risk of drug-resistant epilepsy.

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

Download Plain Language Summary

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

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

On June 16 th, 2022, Tabitha Orth, President and Founder of International Autoimmune Encephalitis Society officially became the 7,315 th “point of light”. Recognized for the volunteer work she and IAES has done to spark change and improve the world for those touched by Autoimmune Encephalitis. The award was founded by President George H.W. Bush in 1990.

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

International Autoimmune Encephalitis Society (IAES), home of the AEWarrior®, is the only Family/Patient-centered organization that assists members from getting a diagnosis through to recovery and the many challenges experienced in their journey. Your donations are greatly appreciated and are the direct result of IAES’ ability to develop the first product in the world to address the needs of patients, Autoimmune Encephalitis Trivia Playing Cards. Every dollar raised allows us to raise awareness and personally help Patients, Families, and Caregivers through their Journey with AE to ensure that the best outcomes can be reached. Your contribution to our mission will help save lives and improve the quality of life for those impacted by AE. For this interested in face masks, clothing, mugs, and other merchandise, check out our AE Warrior Store! This online shop was born out of the desire for the AE patient to express their personal pride in fighting such a traumatic disease and the natural desire to spread awareness. Join our AE family and help us continue our mission to support patients, families and caregivers while they walk this difficult journey.

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

The Unique Nature of Seizures in Autoimmune Encephalitis

by tabitha orth | Apr 28, 2020 | Special Series

April-29-2020 | Claudia Lopez Lloreda, PennNeuroKnow

What are seizures?

Seizures can be scary events both for people who suffer from them and for their loved ones. Symptoms of a seizure typically include muscle spasms; loss of consciousness; sudden, rapid eye movements; or sudden mood changes; among other symptoms, and these can last from seconds to minutes¹. These are the most severe seizures, but mild seizures, with more moderate physical and behavioral symptoms — such as stiffness of the muscles, feelings of déjà vu, anxiety, temporary confusion, or nausea — can also happen and may negatively affect health. During seizures, the body parallels what is happening in the brain: uncontrolled movements of the body can result from uncontrolled bursts of electrical activity in the brain.

Seizures are a response to hyperexcitability, meaning increased activity, of neurons in the brain, and hypersynchrony, meaning more neurons fire at the same time than normal. Seizures are very different across and within conditions. They can be generalized, affecting the entire brain from the beginning of the seizure, or focal, affecting one specific area although it may later spread. Frequent, unprovoked seizures called recurrent seizures may indicate that the person has a condition called epilepsy. Epilepsy is a chronic neurological disorder in which seizures can cause periods of unusual behavior, sensations, and negative effects on cognition such as a loss of awareness. However, because abnormal electrical activity can happen in response to other alterations in the brain such as brain injury and in response to medications, seizures can also be seen in other conditions.

One of these conditions is autoimmune encephalitis (AE). In AE, the body attacks the brain by creating antibodies against important neuronal proteins. Because these proteins help neurons communicate, the antibodies alter neuronal activity. Altering neuronal activation can lead to the changes that are seen in seizures (hyperexcitability and hypersynchrony). In fact, research shows that seizures in some patients can be a common symptom during the acute phase (early on in disease) of AE². It is believed that antibodies against the neuronal proteins contribute directly to the disease processes and the development of seizures. It’s also possible that the process of neuroinflammation associated with AE, which increases the amount of toxic inflammatory molecules in the brain, can also contribute to the development of seizures². Even once the inflammation has been resolved, the brain can still be predisposed to seizures or developing epilepsy, especially if the inflammation resulted in neuronal death³. However, whether epilepsy, a chronic disease, is developed in response to AE is not entirely clear. Some studies suggest that the risk of developing chronic epilepsy is low, from 10-15%⁴.

In different types of AE, seizures appear differently. Apart from the well-known tonic-clonic seizures (associated with jerking muscle movements), seizures in AE can also show up as faciobrachial dystonic seizures. These are characterized by abrupt involuntary movements, typically on one half of the face and arm of the same side. The frequency, response to therapies, and symptoms of the seizures themselves can all vary. However, the AE that most frequently manifest with seizures and chronic epilepsy are those mediated by antibodies against the LGI1, GABA_BR, and GABA_AR; all-important proteins involved in neuronal communication⁵.

Are seizures associated with AE treated the same way as in epilepsy?

Antiepileptic drugs are the standard of care for people with epilepsy. Since seizures are a result of uncontrolled electrical activity and an imbalance of excitation and inhibition in the brain, antiepileptic drugs work by trying to restore that balance. For example, the drug clonazepam prevents seizures by increasing the effectiveness of a molecule in the brain called GABA, which helps the brain dampen the uncontrolled brain activity.

Now, although the normal path for people with epilepsy is treatment with antiepileptic drugs, it may not be particularly effective for people with seizures associated with AE. A study looking at a population of AE patients found that resolution of seizures happened even after discontinued antiepileptic drugs therapy⁶. In these young patients with AE who experienced unprovoked seizures at the onset of the disease there was a remission rate of 94%, meaning they stopped suffering from seizures, after they stopped taking antiepileptic drugs. Rather, immunotherapy seemed to be the important factor in controlling seizures. The researchers suggested that “long-term use of antiepileptic drugs appears not to be necessary to control seizures in AE”⁶.

Other studies support the idea that immunotherapy is more effective in attacking seizures in AE. One study looked at three different types of autoimmune encephalitis (anti-LGI1, anti-NMDAR, and anti-GABA_BR) and their response to immunotherapy and antiepileptic drugs⁷. They found that seizure freedom was achieved faster and more frequently after the use of immunotherapy than after the use of antiepileptic drugs. However, there may be a specific window in which immunotherapy is effective at controlling seizures.

Importantly, the researchers do mention that differences in seizures characteristics and therefore response to treatment may be due to the specific type of encephalitis. For example, patients with anti-GABA_BR encephalitis had an increased risk of developing seizures, meaning that the development of seizures may depend on the type of encephalitis⁷.

What do these findings mean for people with AE?

These differences in treatment response between AE and epilepsy point to an important trait that needs to be considered: the cause of seizures. In AE, antibodies generated against important neuronal proteins make the brain go awry. Therefore, one of the most effective ways to treat seizures may be attacking the root of the problem with immunotherapy. However, due to the variable nature of AE and the seizures associated with the condition, proper treatment with immunotherapy and/or antiepileptic medication will change from patient to patient.

What to do if someone is having a seizure?

During the most severe seizures, the person may not be able to control their body movements. For this reason, you may help them clear the area around them to prevent possible injury. If possible, place them on their side and provide cushioning for their head. There are additional indications suggested by the Center for Disease Control (become familiar with these here).

Seizures in AE Handout

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

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

References

Epilepsy. (2019, August 10). Retrieved March 6, 2020, from https://www.mayoclinic.org/diseases-conditions/epilepsy/symptoms-causes/syc-20350093
Rana, A., & Musto, A. E. (2018). The role of inflammation in the development of epilepsy. Journal of Neuroinflammation, 15(1). doi: 10.1186/s12974-018-1192-7
Vezzani, A., Fujinami, R. S., White, H. S., Preux, P.-M., Blümcke, I., Sander, J. W., & Löscher, W. (2015). Infections, inflammation and epilepsy. Acta Neuropathologica, 131(2), 211–234. doi: 10.1007/s00401-015-1481-5
Steriade, C., Moosa, A. N., Hantus, S., Prayson, R. A., Alexopoulos, A., & Rae-Grant, A. (2018). Electroclinical features of seizures associated with autoimmune encephalitis. Seizure, 60, 198–204. doi: 10.1016/j.seizure.2018.06.021
Spatola, M., & Dalmau, J. (2017). Seizures and risk of epilepsy in autoimmune and other inflammatory encephalitis. Current Opinion in Neurology, 30(3), 345–353. doi: 10.1097/wco.0000000000000449
Huang, Q., Ma, M., Wei, X., Liao, Y., Qi, H., Wu, Y., & Wu, Y. (2019). Characteristics of Seizure and Antiepileptic Drug Utilization in Outpatients with Autoimmune Encephalitis. Frontiers in Neurology, 9. doi: 10.3389/fneur.2018.01136
Bruijn, M. A. D., Sonderen, A. V., Coevorden-Hameete, M. H. V., Bastiaansen, A. E., Schreurs, M. W., Rouhl, R. P., … Titulaer, M. J. (2019). Evaluation of seizure treatment in anti-LGI1, anti-NMDAR, and anti-GABABR encephalitis. Neurology, 92(19). doi: 10.1212/wnl.0000000000007475

Cover Image from Pixabay: https://pixabay.com/illustrations/epilepsy-seizure-stroke-headache-623346/

KETO Diet: What is it? Who is it for? And why?

by tabitha orth | Jan 28, 2020 | Hot Topics

January-28-2020 | Daria Muir, M.D.

It is important that we all stay well informed. When a person receives a diagnosis of autoimmune encephalitis, they want to do whatever they can to improve their health. Some will reach for what appears to them to be a positive action and decide to change their diet. This can have very negative unintended consequences. To ensure your safety, and in IAES’ commitment to providing accurate information to assist you in being well informed on your road to recovery, today I’m going to give you a simple explanation about the Keto Diet.

What is it?

KETO is a diet that excludes carbohydrates completely. Basically, you eat just proteins and fats. Carbohydrates are the main fuel generator for the body (and especially the brain). They transform into glucose (the fuel). By switching to the KETO diet, one leaves the body without the fuel source. So, the body learns to turn other stuff into fuel. In this case, mainly fat. But also, the muscles. That’s what we call “putting the body into a state ok Ketosis). Is this good? Is it bad? For some people it is good. For some it is bad. For some it is an unnecessary risk, meaning there is no proof whatsoever that it helps, but there is proof that it can do some damage.

Who is a candidate for the Keto Diet?

Keto diet is recommended in a small number of diseases:

– severe Epilepsy, irresponsive to golden standard medication (being more efficient in children);

– Glucose Transporter Type 1 Deficiency Syndrome (a genetical disease that does not allow the body to produce GluT1 , so the brain does not get glucose- fuel. The ONLY treatment in this situation is keto diet!);

– it is also used by some nutritionists with patients that need to lose weight.

!!!! It needs to be assessed, recommended and monitored by a doctor!!!

There is no proof that the KETO Diet works in Autoimmune Encephalitis. (It can be recommended in severe Epilepsy post-Acquired Brain Injury in AE, but it does not treat AE, it treats the Epilepsy resulted from a brain injury from AE. As you know by now, Epilepsy and Seizures are not the same things. In AE we may have seizures, due to brain swelling and antibodies attacking our healthy brain cell. This is why we need immunosuppressant/ immunomodulatory treatment to control the disease.

Epilepsy is a disease resulted from the brain being injured and scarred.

Epilepsy can happen in AE but having seizures does not mean you have Epilepsy! Your doctor needs to asses that and tell you that you acquired Epilepsy!

Why? And why not the KETO Diet?

Now that you understand who an appropriate candidate for the Keto Diet would be, let’s discuss what can happen if you try the diet on your own without discussing it with your doctor.

Why does the Keto Diet need to be recommended by your doctor and monitored all the time?

Because it can be dangerous! Yes, it can be.

For diabetics. Also, people with kidney disease or who take medication that increases the risk of Kidney disease. For example, It can lead to major weight loss, below the normal BMI, that can endanger hormonal balance. It can increase pressure on the liver and kidney and eventually eats up your muscles too. The body can enter into ketosis (dangerous for some people).

KETO Diet is not easy, not harmless, not for anybody and not proven effective in AE.

Your doctor needs to assess and recommend that for you or for your child because it can be dangerous and can cause harm. If you have the conditions stated at point 2, then you might benefit from a very well supervised KETO Diet. Always ask your doctor! And please, don’t recommend it to other people, because it can harm them! Our concern is your safety and sharing accurate information for your best overall health.

References:

Ketogenic Diet and Epilepsy: What We Know So Far

Ketogenic Diet in Patients with GLUT1 Deficiency Syndrome

Ketogenic Diet

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

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

After 25 Years, a Proper Diagnosis-Autoimmune Encephalitis!

by Melody Wilson | Oct 29, 2019 | AE Warrior Personal Stories

October 30-2019 | Lauren Mabry

In 1994 when I was 9 years old I was diagnosed with Epilepsy with partial complex seizures after my mom witnessed a bizarre event where my arm jerked wildly and I fell to the ground. These events occurred multiple times and I underwent EEG testing, MRI, and all the tests came back normal. We tried a few anti-epileptic drugs and eventually found one that seemed to stop the episodes. Fast-forward a few years and I started to have breakthrough seizures…

This became the routine: find a drug that worked, maybe have a breakthrough seizure, up the dose, breakthrough, worry about having a breakthrough, or maybe go years and be fine.Things were challenging for me off and on throughout college as I seemed to be unable to stabilize my episodes for a year or two. And then I was fine for many years up until I was told I had to switch medication to get pregnant and so I did. I switched to the “safest’ medication and things seemed to be fine until about halfway through my pregnancy with my first son in 2015 and then things went haywire. I suffered these partial seizures every ten minutes. I hardly slept. I had to go on short term disability from my job at 5 months pregnant. I could barely speak. Eventually things semi-stabilized.

The goal was always to go back on Topamax, the drug I had been on before my pregnancies as it had been working, but when I finally switched back to this drug in November 2018 my body appeared to just reject it and instead I just started to have multiple episodes per day. My doctor. sent me to the hospital for inpatient video EEG monitoring. I was in the hospital for about 3.5 days where I had 87 episodes. I barely slept.

On the last day in the hospital my doctor took bloodwork for an autoimmune panel. It was the last thing we did while I was in the hospital and at the time I barely thought anything of it. At my follow-up appointment my neurologist told me I have autoimmune encephalitis – my brain is on fire. We did a round of prednisone steroids where I could literally feel my brain cooling down. Within a couple of days of being on the prednisone my seizures that I had experienced multiple times a day for 4 years stopped completely. We followed up the oral prednisone with IV Solu-Medrol and it’s now been 8 months and I’m still seizure free AND off my anti-epileptic medications.

Autoimmune encephalitis is still a very new disease in its infancy of research. It wasn’t even discovered and published until almost 12 years after my initial diagnosis of epilepsy. I saw neurologists in VA, at Johns Hopkins, and UCLA over the years and it wasn’t until I moved to Pittsburgh, PA that I was finally properly diagnosed. I don’t say this to place blame on any of my previous doctors, but to raise awareness that it can save your life to get a second or even third opinion about what is going on in your body.

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

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

Have You Thought About Clinical Trials?

by Melody Wilson | Feb 10, 2017 | Hot Topics

February 10, 2017

ezgif 5 8c88a70b0ef8 - Have You Thought About Clinical Trials?

Sometimes clinical trials go past us and we hesitate to participate because we don’t really understand how they work and what is involved.

Only through scientific investigation can we hope for new treatments and protocols to be developed. Participants contribute to these discoveries. The link below leads to an article from the Epilepsy Foundation but is a simple and thorough explanation of all clinical trials. I urge you to get the facts and if offered the chance to participate consider being a part of how science can help victims of AE.

http://www.epilepsy.com/article/2017/1/what-clinical-research

Psychiatric Manifestations of Autoimmune Encephalitis

WHY WE DID THIS WORK

Anti-NMDAR encephalitis

Anti-LGI1 encephalitis

Anti-CASPR encephalitis

Anti-AMPAR encephalitis

Anti-GABA-A encephalitis

Anti-GABA-B encephalitis

Anti-DPPX encephalitis

Anti-mGluR5 encephalitis

Anti-Neurexin-3a encephalitis

Diagnosis and treatment

What do the findings mean?

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Rare and Seronegative Autoimmune Encephalitis

WHY WE DID THIS WORK

WHAT WE FOUND

HOW CAN WE USE THIS RESEARCH

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

Epilepsy and Autoimmune Encephalitis

How we did this work

What were the interesting things we found

What do these findings mean?

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

Are seizures associated with AE treated the same way as in epilepsy?

What do these findings mean for people with AE?

What to do if someone is having a seizure?

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

What is it?

Who is a candidate for the Keto Diet?

!!!! It needs to be assessed, recommended and monitored by a doctor!!!

Why? And why not the KETO Diet?

Why does the Keto Diet need to be recommended by your doctor and monitored all the time?

KETO Diet is not easy, not harmless, not for anybody and not proven effective in AE.

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

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

Your Tax deductible donations help us save lives and quality of lives.

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