AntiNMDA
24.9K views | +2 today
Follow
 
Scooped by Nesrin Shaheen
onto AntiNMDA
Scoop.it!

Not so rare - Autoimmune encephalitis is as common as infectious encephalitis | LinkedIn

Not so rare - Autoimmune encephalitis is as common as infectious encephalitis | LinkedIn | AntiNMDA | Scoop.it
Once considered a rare disease class, new findings suggest that autoimmune encephalitis (AE) is much more common than previously thought. AE is a
No comment yet.
AntiNMDA
Your new post is loading...
Scooped by Nesrin Shaheen
Scoop.it!

Clinical spectrum of high-titre GAD65 antibodies | Journal of Neurology, Neurosurgery & Psychiatry

Neuro-inflammation Original research Clinical spectrum of high-titre GAD65 antibodies http://orcid.org/0000-0003-4860-0470Adrian Budhram1, http://orcid.org/0000-0003-4698-663XElia Sechi2,3, http://orcid.org/0000-0002-6661-2910Eoin P Flanagan2, Divyanshu Dubey4, Anastasia Zekeridou2, Shailee S Shah2, Avi Gadoth5, http://orcid.org/0000-0001-6212-1236Elie Naddaf2, http://orcid.org/0000-0001-6856-8143Andrew McKeon2, http://orcid.org/0000-0002-6140-5584Sean J Pittock6, Nicholas L Zalewski2 Clinical Neurological Sciences, Western University Schulich School of Medicine and Dentistry, London, Ontario, Canada Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Sassari, Italy Neurology and Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA Mayo Clinic, Rochester, Minnesota, USA Correspondence to Dr Nicholas L Zalewski, Neurology, Mayo Clinic Minnesota, Rochester, MN 55905, USA; zalewski.nicholas{at}mayo.edu Abstract Objective To determine clinical manifestations, immunotherapy responsiveness and outcomes of glutamic acid decarboxylase-65 (GAD65) neurological autoimmunity. Methods We identified 323 Mayo Clinic patients with high-titre (>20 nmol/L in serum) GAD65 antibodies out of 380 514 submitted anti-GAD65 samples (2003–2018). Patients classified as having GAD65 neurological autoimmunity after chart review were analysed to determine disease manifestations, immunotherapy responsiveness and predictors of poor outcome (modified Rankin score >2). Results On review, 108 patients were classified as not having GAD65 neurological autoimmunity and 3 patients had no more likely alternative diagnoses but atypical presentations (hyperkinetic movement disorders). Of remaining 212 patients with GAD65 neurological autoimmunity, median age at symptom onset was 46 years (range: 5–83 years); 163/212 (77%) were female. Stiff-person spectrum disorders (SPSD) (N=71), cerebellar ataxia (N=55), epilepsy (N=35) and limbic encephalitis (N=7) could occur either in isolation or as part of an overlap syndrome (N=44), and were designated core manifestations. Cognitive impairment (N=38), myelopathy (N=23) and brainstem dysfunction (N=22) were only reported as co-occurring phenomena, and were designated secondary manifestations. Sustained response to immunotherapy ranged from 5/20 (25%) in epilepsy to 32/44 (73%) in SPSD (p=0.002). Complete immunotherapy response occurred in 2/142 (1%). Cerebellar ataxia and serum GAD65 antibody titre >500 nmol/L predicted poor outcome. Interpretation High-titre GAD65 antibodies were suggestive of, but not pathognomonic for GAD65 neurological autoimmunity, which has discrete core and secondary manifestations. SPSD was most likely to respond to immunotherapy, while epilepsy was least immunotherapy responsive. Complete immunotherapy response was rare. Serum GAD65 antibody titre >500 nmol/L and cerebellar ataxia predicted poor outcome. Statistics from Altmetric.com View Full Text Footnotes Contributors AB designed/conceptualised the study, acquired/analysed the data, drafted the manuscript and composed the tables/figures. ES, EPF, DD, AZ, SSS, AG, EN and AM acquired/analysed the data, and revised the manuscript for intellectual content. SJP and NLZ designed/conceptualised the study, acquired/analyzed the data, revised the manuscript for intellectual content and supervised the study. Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. Competing interests AB has no disclosures to report. ES has no disclosures to report. EPF is a site principal investigator in a randomised placebo-controlled clinical trial of Inebilizumab (A CD19 inhibitor) in neuromyelitis optica spectrum disorders funded by MedImmune/Viela Bio. He receives no personal compensation and just receives reimbursement for the research activities related to the trial. DD has a patent pending for Kelch-like protein 11 as a marker of neurological autoimmunity and has received research support from Grifols, Translational Research Innovation and Test Development Office and, Center for Clinical and Translational Science. DD has consulted for UCB and Astellas. All compensation for consulting activities is paid directly to Mayo Clinic. AZ has a patent pending for PDE10A-IgG as a biomarker of neurological autoimmunity. SS has no disclosures to report. AG has a patent pending for MAP1B IgG as a biomarker of neurological autoimmunity and small-cell lung cancer. EN has no disclosures to report. AM reports grants from Alexion, grants from Grifols, grants from Euroimmun, outside the submitted work; in addition, AM has a patent for Septin-5-IgG pending, a patent for PDE10A-IgG pending, a patent for MAP1B-IgG pending, and a patent for GFAP-IgG pending. SJP reports grants, personal fees and non-financial support from Alexion Pharmaceuticals; grants from Grifols, Autoimmune Encephalitis Alliance; grants, personal fees, non-financial support and other from MedImmune; SJP has a patent (patent #8889102) (application#12-678350) on neuromyelitis optica autoantibodies as a marker for neoplasia, and also a patent (patent #9891219B2) (application#12-573942) on methods for treating neuromyelitis optica (NMO) by administration of eculizumab to an individual that is aquaporin-4 (AQP4)-IgG autoantibody positive; SJP also has patents pending for the following IgGs as biomarkers of autoimmune neurological disorders (septin-5, Kelch-like protein 11, GFAP, PDE10A and MAP1B). NLZ has no disclosures to report. Patient consent for publication Not required. Ethics approval This study was approved by the institutional review board of the Mayo Clinic, Rochester, Minnesota. Provenance and peer review Not commissioned; externally peer reviewed. Data availability statement Data are available on reasonable request. Deidentified participant data will be made available to any qualified investigator on reasonable request directed to the corresponding author (NLZ). Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise. Request Permissions If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways. Copyright information: © Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ. Read the full text or download the PDF: Subscribe Log in
Madelaudrey's curator insight, February 15, 3:20 AM
https://expressonlinemedicine.com/ https://expressonlinemedicine.com/shop/ https://expressonlinemedicine.com/product/buy-adderall-online/ https://expressonlinemedicine.com/product/ritalin/ https://expressonlinemedicine.com/product/buy-vyvanse-pills-online/ https://expressonlinemedicine.com/product/buy-arimidex-online/ https://expressonlinemedicine.com/product/buy-ativan-online/ https://expressonlinemedicine.com/product/buy-diazepam-online/ https://expressonlinemedicine.com/product/buy-green-xanax-online/ https://expressonlinemedicine.com/product/buy-greenstone-xanax-online/ https://expressonlinemedicine.com/product/buy-helex-online/ https://expressonlinemedicine.com/product/buy-klonopin-online/ https://expressonlinemedicine.com/product/buy-xanax-online/ https://expressonlinemedicine.com/product/buy-yellow-xanax-bars-online/ https://expressonlinemedicine.com/product/buy-aliaxin-1ml-online/ https://expressonlinemedicine.com/product/buy-juvederm-volbella-le-online/ https://expressonlinemedicine.com/product/buy-juvederm-ultra-1ml-online/ https://expressonlinemedicine.com/product/lidocaine/ https://chemistpoisonshop.com/ http://www.420kushsociety.com/ https://expressonlinemedicine.com/product/buy-methadone-online/ https://expressonlinemedicine.com/product/buy-botox-online/ https://expressonlinemedicine.com/product/buy-neurobloc-online/ https://expressonlinemedicine.com/product/buy-dysport-online/ https://expressonlinemedicine.com/product/buy-methadone-online/ https://expressonlinemedicine.com/product/cbd-oil/ https://expressonlinemedicine.com/product/buy-rohypnol-online/ https://expressonlinemedicine.com/product/generic-finasteride/ https://expressonlinemedicine.com/product/buy-efavirenz-online/ https://expressonlinemedicine.com/product/buy-emtricitabine-online/ https://expressonlinemedicine.com/product/buy-lamivudine-online/ https://expressonlinemedicine.com/product/buy-tenofovir-online/ https://expressonlinemedicine.com/product/buy-ambien-online/ https://chemistpoisonshop.com/ https://expressonlinemedicine.com/product/buy-modafinil-online/ https://expressonlinemedicine.com/product/buy-stilnox-online/ https://expressonlinemedicine.com/product/buy-zopiclone-online/ https://expressonlinemedicine.com/product/buy-suboxone-online/ https://expressonlinemedicine.com/product/buy-subutex-online/ https://expressonlinemedicine.com/product/buy-codeine-online/ https://expressonlinemedicine.com/product/buy-demerol-online/ https://expressonlinemedicine.com/product/buy-diamorphine-online/ https://expressonlinemedicine.com/product/buy-dilaudid-online/ https://expressonlinemedicine.com/product/buy-endocet-online/ https://expressonlinemedicine.com/product/buy-fentanyl-patches-online/ https://expressonlinemedicine.com/product/buy-hydrocodone-online/ https://expressonlinemedicine.com/product/buy-lortab-online/ https://expressonlinemedicine.com/product/buy-methadone-online/ https://expressonlinemedicine.com/product/buy-mobic-online/ https://expressonlinemedicine.com/product/buy-morphine-sulfate-online/ https://expressonlinemedicine.com/product/buy-morphine-sulphate-injection/ https://expressonlinemedicine.com/product/buy-norco-online/ https://expressonlinemedicine.com/product/buy-opana-online/ https://expressonlinemedicine.com/product/buy-oxycodone-online/ https://expressonlinemedicine.com/product/buy-oxycontin-online/ https://expressonlinemedicine.com/product/buy-oxynorm-online/ https://expressonlinemedicine.com/product/buy-percocet-online/ https://expressonlinemedicine.com/product/buy-rheumacure-online/ https://expressonlinemedicine.com/product/buy-roxicodone-online/ http://www.420kushsociety.com/ http://www.420kushsociety.com/ https://chemistpoisonshop.com/ https://expressonlinemedicine.com/product/buy-vicodin-online/ https://expressonlinemedicine.com/product/buy-flakka-a-pvp-online/ https://expressonlinemedicine.com/product/diapers/ https://expressonlinemedicine.com/product/buy-adipex-online/ https://expressonlinemedicine.com/product/buy-garcinia-cambogia-extract-online/ https://expressonlinemedicine.com/product/buy-phentermine-online/ https://expressonlinemedicine.com/product/buy-xls-medical-max-strength-tablets-of-360/ https://lovelyteacuppuppies.com/ https://lovelyteacuppuppies.com/shop/ https://lovelyteacuppuppies.com/product/teacup-maltese-for-sale/ https://lovelyteacuppuppies.com/product/maltese-puppies-for-sale/ https://lovelyteacuppuppies.com/product/teacup-maltese-for-adoption/ https://lovelyteacuppuppies.com/product/puppy-store-near-me/ https://lovelyteacuppuppies.com/product/teacup-maltipoo-for-adoption/ https://lovelyteacuppuppies.com/product/maltipoo-puppies-for-sale/ https://lovelyteacuppuppies.com/product/puppies-for-sale-in-usa/ https://lovelyteacuppuppies.com/product/teacup-poodle/ https://lovelyteacuppuppies.com/product/poodle-puppies-for-sale/ https://lovelyteacuppuppies.com/product/poodle-puppies-for-adoption/ https://lovelyteacuppuppies.com/product/teacup-poodle-puppies-for-sale/ https://genuindocuments.com https://genuindocuments.com/buy-drivers-license-online/ https://genuindocuments.com/buy-academic-diplomas/ https://genuindocuments.com/buy-passport-online/ https://genuindocuments.com/residence-permit-online/ https://genuindocuments.com/diplomatic-passport/ https://genuindocuments.com/id-cards/ https://ssn-id-us.com/ https://ssn-id-us.com/shop/ https://ssn-id-us.com/product/buy-nclex-without-exam/ https://ssn-id-us.com/product/buy-ssn/ https://ssn-id-us.com/product/buy-canadian-drivers-license/ https://ssn-id-us.com/product/buy-usa-drivers-license/ https://chemistpoisonshop.com/shop/ https://chemistpoisonshop.com/ https://chemistpoisonshop.com/product/buy-arsenic-poison-online/ https://chemistpoisonshop.com/product/buy-botulinum-toxin-online/ https://chemistpoisonshop.com/product/buy-brodifacoum-poison/ https://chemistpoisonshop.com/product/buy-strychnine-poison-online/ https://chemistpoisonshop.com/product/buy-cyanide-poison-online/ https://chemistpoisonshop.com/product/buy-dimethyl-mercury-online/ https://chemistpoisonshop.com/product/buy-lsd-liquid-online/ https://chemistpoisonshop.com/product/buy-maitotoxin-poison-online/ https://chemistpoisonshop.com/product/buy-ricin-poison-online/ https://chemistpoisonshop.com/product/buy-tetrodotoxin-poison-online/ https://chemistpoisonshop.com/product/buy-vx-poison-online/ https://chemistpoisonshop.com/product/buy-polonium-poison-online/ https://expressonlinedocument.com/ https://expressonlinedocument.com/buy-id-card-online/ https://expressonlinedocument.com/buy-drivers-license-online/ https://expressonlinedocument.com/buy-green-card-online/ https://expressonlinedocument.com/buy-real-ssn/ https://expressonlinedocument.com/buy-residence-permit-online/ https://expressonlinedocument.com/buy-passport-online/ http://www.420kushsociety.com/
Scooped by Nesrin Shaheen
Scoop.it!

Prevalence of Autoimmune Encephalitis: Divyansha Dubey, MBBS | Neurology Live

Prevalence of Autoimmune Encephalitis: Divyansha Dubey, MBBS | Neurology Live | AntiNMDA | Scoop.it
The assistant professor of neurology at Mayo Clinic detailed his presentation at ACTRIMS 2021 Forum on the rising prevalence of autoimmune encephalitis.
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Discover Encephalitis: what it is & how you can help – Brain Based

Discover Encephalitis: what it is & how you can help – Brain Based | AntiNMDA | Scoop.it
It’s World Encephalitis Day! Wait – what is encephalitis? 78% of people across the world do not know what encephalitis is and this has to change! 500,000 children and adults are affected by encephalitis every year – that means one person every minute. The death rates for encephalitis are high and survivors are often left with an acquired brain injury, often resulting in memory problems, personality changes, epilepsy, fatigue, as well as emotional, behavioural, and cognitive difficulties. The term encephalitis refers to inflammation of the brain, commonly caused by a viral infection. The exact cause of encephalitis remains unknown. There are two main types of encephalitis: Primary encephalitis: occurring when a virus or other agent directly infects the brain. Secondary encephalitis: resulting from a faulty immune system reaction elsewhere in the body, where one’s immune system starts to attack healthy cells in the brain. This often occurs 2-3 weeks after the initial infection. Encephalitis often presents with mild flu-like symptoms, including headache and fever, but sometimes there are no signs at all. Other more severe symptoms can include disordered thinking, seizures, movement difficulties, paralysis, weakness, and more. A diagnosis can generally be made based on symptoms, as well as using blood tests, medical imaging and cerebrospinal fluid analyses. What causes encephalitis? Common viral causes include: Herpes simplex virus (HSV), including both HSV-1 (associated with cold sores and fever blisters) and HSV-2 (associated with genital herpes). Other herpes viruses, including the Epstein-Barr virus and the varicella-zoster virus. Enteroviruses, including the poliovirus and the coxsackievirus. Mosquito-borne viruses, causing infections such as St. Louis, West Nile, La Crosse, western equine and eastern equine encephalitis. Tick-borne viruses Rabies virus Childhood infections, such as measles, mumps and German measles, although these are now rare due to the availability of vaccines. Although anyone can develop encephalitis, a few risk factors have been identified: Weakened immune system: people with HIV/AIDS, for example, who take immune-suppressing drugs are at an increased risk, as well as individuals with conditions causing a weakened immune system. Age: in general, younger children and older adults are at an increased risk of encephalitis. Geographical regions: certain regions of the world are more prone to encephalitis causes, such as mosquito- or tick-borne viruses. Time of year: as mosquito- and tick-borne diseases are more common during certain seasons. Encephalitis can be treated using antiviral medications (if caused by a virus), antibiotics (if caused by bacteria), steroids to reduce brain swelling, sedatives for restlessness, acetaminophen for fever, as well as physical and occupational therapy if the brain is affected post-infection.  How can I protect myself and others? There are a few precautions that can be taken to avoid the viruses that cause this disease. Firstly, vaccinations! Keep your own and your children’s vaccinations current, especially before traveling to a new destination. Consult with your doctor about your plans to travel and how you can protect yourselves. Practicing good hygiene is also important, involving frequent and thorough hand washing. One should also not share utensils with others, such as tableware and beverages. Protect yourself and your children against mosquitoes and ticks. This involves dressing for protection (wear long-sleeved shirt and long pants), apply mosquito repellent, use insecticides, and refrain from unnecessary activity in places where mosquitoes are common. So, why should we be celebrating this disease? World Encephalitis Day is not about celebrating the disease, it is about raising awareness and showing support towards individuals affected, as well as those who have been supporting or lost loved ones. World Encephalitis Day was founded by the Encephalitis Society in 2014 and is held on the 22nd of February each year. It was founded with the following statement: “It is our hope that it will play a leading role in our mission to increase global awareness of encephalitis and therefore saving lives and building better futures.” To support their mission today, you can share social media posts about World Encephalitis Day to help raise awareness. Use the hashtags #WorldEncephalitisDay and #Red4WED on Instagram, TikTok, Twitter, Facebook, LinkedIn and more! Where can I learn more? Explore the Encephalitis Society’s website to learn about how you can get help if you or someone you are close to is living with encephalitis, or learn how you can make a difference: https://www.encephalitis.info/  The Encephalitis Society offers a number of ways to get involved, including raising awareness, fundraising, donating, volunteering, and more! You can also check out these two educational books on encephalitis: ‘Brain on Fire: My Month of Madness’ by Susannah Cahalan is an autobiography about her struggle with a rare form of encephalitis and her recovery. This book was also adapted into a homonymous 2016 movie starring Chloe Grace Moretz. ‘Life After Encephalitis’ by Dr Ava Easton provides information on different types of encephalitis and describes the experiences of those affected by encephalitis, with powerful narratives of survivors and family members. Featured Image Source: Kelley, et al. (2017). Autoimmune Encephalitis: Pathophysiology and Imaging Review of an Overlooked Diagnosis. American Journal of Neuroradiology. Two Video Sources: Encephalitis Society on YouTube https://www.youtube.com/c/EncephalitisSociety/featured Edited by Cyrus Rohani-Shukla
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Clinical features and management of coexisting anti-N-methyl-D-aspartate receptor encephalitis and myelin oligodendrocyte glycoprotein antibody-associated encephalomyelitis: a case report and revie...

Clinical features and management of coexisting anti-N-methyl-D-aspartate receptor encephalitis and myelin oligodendrocyte glycoprotein antibody-associated encephalomyelitis: a case report and revie... | AntiNMDA | Scoop.it
The rates of coexisting anti-NMDA receptor encephalitis and MOG antibody-associated encephalomyelitis may be underestimated.Clinical symptoms such as seizures and cognitive decline accompanied by atypical central nervous system demyelination serve as warning signs of possible coexisting anti-NMDA...
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

The clinical features, underlying immunology, and treatment of autoantibody‐mediated movement disorders - Damato - 2018 - Movement Disorders - Wiley Online Library

The clinical features, underlying immunology, and treatment of autoantibody‐mediated movement disorders - Damato - 2018 - Movement Disorders - Wiley Online Library | AntiNMDA | Scoop.it
ABSTRACT An increasing number of movement disorders are associated with autoantibodies. Many of these autoantibodies target the extracellular domain of neuronal surface proteins and associate with ...
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

The long‐term outcome of neuropsychological function is favorable in patients with non‐malignancy related anti-GABA B R encephalitis: a case series | BMC Neurology | Full Text

The long‐term outcome of neuropsychological function is favorable in patients with non‐malignancy related anti-GABA B R encephalitis: a case series | BMC Neurology | Full Text | AntiNMDA | Scoop.it
Background Anti-GABABR encephalitis is a rare type of autoimmune encephalitis, which often presents with memory impairments, behavioral changes and seizures. This case series describes the neuropsychological function recovery pattern in five adult patients with anti-GABABR encephalitis. Case presentation We recruited five patients with clinically confirmed anti-GABABR encephalitis without any accompanying malignancy. Comprehensive neuropsychological evaluation was conducted on each patient. All the five patients were evaluated in the chronic phase. Five age and gender matched healthy adults were recruited as control group. Our study demonstrated that the neuropsychological function of the patients with anti-GABABR encephalitis was no different with respect to the control group during the chronic phase (more than 6 months after onset). Moreover, one patients with neuropsychological evaluation at acute (within 2 months after onset of symptoms), post-acute (2 to 6 months after onset) and chronic phases respectively, presented neuropsychological function recovered as early as in the post-acute phase and only showed cognition impairment in the acute phase. Conclusions The results of this retrospective study indicate a favorable long-term neuropsychological function outcome in adult patients with anti-GABABR encephalitis, despite severe memory deficits occurring during the acute phase. These findings improve our understanding related to the prognosis of neuropsychological function in anti-GABABR encephalitis.
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Why Am I So Tired? | Psychology Today Canada

Why Am I So Tired? | Psychology Today Canada | AntiNMDA | Scoop.it
Dealing with the pandemic can be exhausting. Here are strategies to deal with stress and fatigue.
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Understanding the clinical features that help to predict surface-directed autoantibodies | Physician's Weekly

Understanding the clinical features that help to predict surface-directed autoantibodies | Physician's Weekly | AntiNMDA | Scoop.it
The study aims to generate a score to assess the clinical features that help identify the surface-directed autoantibodies in subjects with new-onset focal epilepsy. It also aims to understand immunotherapy’s value. It is a prospective study of autoantibody evaluation in 219 patients having new-onset focal epilepsy. 10.53% of the subjects (23 adults) had detectable serum autoantibodies. 9 out of those individuals had encephalitis. None of the patients were without autoantibodies. The study identified six elements that will help to predict the autoantibody positivity, namely, age, lowered self-reported mood, ictal piloerection, MRI limbic changes, conventional risk factor absence, and decreased attention. 79% (11 out of 14) of the subjects had detectable autoantibodies, but no encephalitis. They showed superior outcomes than those with confirmed encephalitis. Mood phenotype, inflammatory investigation, cognitive phenotypes, and seizure semiology help to identify the surface autoantibodies. The outcome of the treatment was excellent in those without the condition but with positive autoantibody. Thus, the study recommends that the healthcare provider should offer the treatment based on the encephalitis’ clinical features and not the presence of positive autoantibody. According to this study, the immunotherapy-responsive epilepsy syndromes with positive autoantibodies come under autoimmune encephalitis. Ref: https://jnnp.bmj.com/content/early/2020/11/29/jnnp-2020-325011
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Cross-reactivity of a pathogenic autoantibody to a tumor antigen in GABAA receptor encephalitis | PNAS

Cross-reactivity of a pathogenic autoantibody to a tumor antigen in GABAA receptor encephalitis | PNAS | AntiNMDA | Scoop.it
RESEARCH ARTICLE Cross-reactivity of a pathogenic autoantibody to a tumor antigen in GABAA receptor encephalitis Simone M. Brändle, Manuela Cerina, View ORCID ProfileSusanne Weber, View ORCID ProfileKathrin Held, Amélie F. Menke, Carmen Alcalá, View ORCID ProfileDavid Gebert, View ORCID ProfileAlexander M. Herrmann, Hannah Pellkofer, View ORCID ProfileLisa Ann Gerdes, View ORCID ProfileStefan Bittner, View ORCID ProfileFrank Leypoldt, View ORCID ProfileBianca Teegen, View ORCID ProfileLars Komorowski, View ORCID ProfileTania Kümpfel, View ORCID ProfileReinhard Hohlfeld, View ORCID ProfileSven G. Meuth, View ORCID ProfileBonaventura Casanova, View ORCID ProfileNico Melzer, View ORCID ProfileEduardo Beltrán, and View ORCID ProfileKlaus Dornmair PNAS March 2, 2021 118 (9) e1916337118; https://doi.org/10.1073/pnas.1916337118 Edited by Lawrence Steinman, Stanford University School of Medicine, Stanford, CA, and approved January 11, 2021 (received for review June 19, 2020) Article Figures & SI Info & Metrics PDF Significance Antibodies recognizing the neuronal gamma-aminobutyric acid A receptor (GABAA-R) cause severe encephalitis by triggering internalization of the antibody–receptor complexes in inhibitory synapses, which leads to hyperexcitability and dysfunction of neuronal networks. From the cerebrospinal fluid of a patient with GABAA-R encephalitis we cloned a highly expressed antibody and showed that it binds the GABAA-R and influences signal transduction in neurons, explaining clinical symptoms. Using several experimental techniques, we confirmed that the antibody cross-reacts to an oncoprotein which is known to be involved in several malignancies. We showed that cross-reactivity to this oncoprotein may also be detected in two other GABAA-R patients, suggesting that such cross-reactivity is presumably a key event in the pathogenesis of GABAA-R encephalitis. Abstract Encephalitis associated with antibodies against the neuronal gamma-aminobutyric acid A receptor (GABAA-R) is a rare form of autoimmune encephalitis. The pathogenesis is still unknown but autoimmune mechanisms were surmised. Here we identified a strongly expanded B cell clone in the cerebrospinal fluid of a patient with GABAA-R encephalitis. We expressed the antibody produced by it and showed by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry that it recognizes the GABAA-R. Patch-clamp recordings revealed that it tones down inhibitory synaptic transmission and causes increased excitability of hippocampal CA1 pyramidal neurons. Thus, the antibody likely contributed to clinical disease symptoms. Hybridization to a protein array revealed the cross-reactive protein LIM-domain-only protein 5 (LMO5), which is related to cell-cycle regulation and tumor growth. We confirmed LMO5 recognition by immunoprecipitation and ELISA and showed that cerebrospinal fluid samples from two other patients with GABAA-R encephalitis also recognized LMO5. This suggests that cross-reactivity between GABAA-R and LMO5 is frequent in GABAA-R encephalitis and supports the hypothesis of a paraneoplastic etiology. Footnotes ↵1S.M.B., M.C., and S.W. contributed equally to this work. ↵2N.M., E.B., and K.D. contributed equally to this work. ↵3To whom correspondence may be addressed. Email: Klaus.Dornmair{at}med.uni-muenchen.de. Author contributions: R.H., S.G.M., B.C., N.M., E.B., and K.D. designed research; S.M.B., M.C., S.W., K.H., A.F.M., D.G., A.M.H., B.T., and E.B. performed research; C.A., H.P., L.A.G., S.B., F.L., L.K., T.K., B.C., and N.M. contributed new reagents/analytic tools; S.M.B., M.C., S.W., K.H., A.F.M., D.G., A.M.H., B.T., R.H., S.G.M., N.M., E.B., and K.D. analyzed data; and R.H., S.G.M., N.M., E.B., and K.D. wrote the paper. The authors declare no competing interest. This article is a PNAS Direct Submission. This article contains supporting information online at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.1916337118/-/DCSupplemental. Data Availability All study data are included in the article and/or SI Appendix. Published under the PNAS license. View Full Text References ↵ J. Dalmau, F. Graus, Antibody-mediated encephalitis. N. Engl. J. Med. 378, 840–851 (2018).OpenUrlCrossRefPubMed ↵ N. Melzer, S. G. Meuth, H. Wiendl, Paraneoplastic and non-paraneoplastic autoimmunity to neurons in the central nervous system. J. Neurol. 260, 1215–1233 (2013).OpenUrl ↵ C. Bost, O. Pascual, J. Honnorat, Autoimmune encephalitis in psychiatric institutions: Current perspectives. Neuropsychiatr. Dis. Treat. 12, 2775–2787 (2016).OpenUrlPubMed ↵ A. Vincent, C. G. Bien, S. R. Irani, P. Waters, Autoantibodies associated with diseases of the CNS: New developments and future challenges. Lancet Neurol. 10, 759–772 (2011).OpenUrlCrossRefPubMed ↵ M. H. van Coevorden-Hameete, E. de Graaff, M. J. Titulaer, C. C. Hoogenraad, P. A. Sillevis Smitt, Molecular and cellular mechanisms underlying anti-neuronal antibody mediated disorders of the central nervous system. Autoimmun. Rev. 13, 299–312 (2014).OpenUrlCrossRefPubMed ↵ M. J. Titulaer et al.; European Federation of Neurological Societies, Screening for tumours in paraneoplastic syndromes: Report of an EFNS task force. Eur. J. Neurol. 18, 19-e3 (2011).OpenUrlPubMed ↵ J. Dalmau, M. R. Rosenfeld, Paraneoplastic syndromes of the CNS. Lancet Neurol. 7, 327–340 (2008).OpenUrlCrossRefPubMed ↵ T. Ohkawa et al., Identification and characterization of GABA(A) receptor autoantibodies in autoimmune encephalitis. J. Neurosci. 34, 8151–8163 (2014). ↵ M. Petit-Pedrol et al., Encephalitis with refractory seizures, status epilepticus, and antibodies to the GABAA receptor: A case series, characterisation of the antigen, and analysis of the effects of antibodies. Lancet Neurol. 13, 276–286 (2014).OpenUrlCrossRefPubMed ↵ P. Pettingill et al., Antibodies to GABAA receptor α1 and γ2 subunits: Clinical and serologic characterization. Neurology 84, 1233–1241 (2015).OpenUrlCrossRefPubMed ↵ K. O’Connor et al., GABAA receptor autoimmunity: A multicenter experience. Neurol. Neuroimmunol. Neuroinflamm. 6, e552 (2019). ↵ C. Zhou et al., Altered cortical GABAA receptor composition, physiology, and endocytosis in a mouse model of a human genetic absence epilepsy syndrome. J. Biol. Chem. 288, 21458–21472 (2013). ↵ M. Spatola et al., Investigations in GABAA receptor antibody-associated encephalitis. Neurology 88, 1012–1020 (2017).OpenUrlPubMed ↵ C. Y. Guo, J. M. Gelfand, M. D. Geschwind, Anti-gamma-aminobutyric acid receptor type A encephalitis: A review. Curr. Opin. Neurol. 33, 372–380 (2020).OpenUrl ↵ M. M. Simabukuro et al., GABAA receptor and LGI1 antibody encephalitis in a patient with thymoma. Neurol. Neuroimmunol. Neuroinflamm. 2, e73 (2015). ↵ E. Lancaster, Encephalitis, severe seizures, and multifocal brain lesions: Recognizing autoimmunity to the GABAA receptor. Neurol. Neuroimmunol. Neuroinflamm. 6, e554 (2019). ↵ A. Bracher et al., An expanded parenchymal CD8+ T cell clone in GABAA receptor encephalitis. Ann. Clin. Transl. Neurol. 7, 239–244 (2020).OpenUrl ↵ J. M. Matthews, K. Lester, S. Joseph, D. J. Curtis, LIM-domain-only proteins in cancer. Nat. Rev. Cancer 13, 111–122 (2013).OpenUrlCrossRefPubMed ↵ Y. Midorikawa et al., Identification of genes associated with dedifferentiation of hepatocellular carcinoma with expression profiling analysis. Jpn. J. Cancer Res. 93, 636–643 (2002).OpenUrlCrossRef ↵ Z. Hu et al., The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genomics 7, 96 (2006).OpenUrlCrossRefPubMed ↵ C. Hoffmann et al., CRP2, a new invadopodia actin bundling factor critically promotes breast cancer cell invasion and metastasis. Oncotarget 7, 13688–13705 (2016).OpenUrl ↵ B. Schlick et al., Serum autoantibodies in chronic prostate inflammation in prostate cancer patients. PLoS One 11, e0147739 (2016).OpenUrl ↵ C. Hoffmann et al., Hypoxia promotes breast cancer cell invasion through HIF-1α-mediated up-regulation of the invadopodial actin bundling protein CSRP2. Sci. Rep. 8, 10191 (2018).OpenUrlCrossRefPubMed ↵ S. J. Wang et al., Cysteine and glycine-rich protein 2 (CSRP2) transcript levels correlate with leukemia relapse and leukemia-free survival in adults with B-cell acute lymphoblastic leukemia and normal cytogenetics. Oncotarget 8, 35984–36000 (2017).OpenUrl ↵ S. M. Brändle et al., Distinct oligoclonal band antibodies in multiple sclerosis recognize ubiquitous self-proteins. Proc. Natl. Acad. Sci. U.S.A. 113, 7864–7869 (2016). ↵ H. B. Michelson, R. K. Wong, Excitatory synaptic responses mediated by GABAA receptors in the hippocampus. Science 253, 1420–1423 (1991). ↵ S. Schuster et al., Fatal PCR-negative herpes simplex virus-1 encephalitis with GABAA receptor antibodies. Neurol. Neuroimmunol. Neuroinflamm. 6, e624 (2019). ↵ S. Sala, C. Ampe, An emerging link between LIM domain proteins and nuclear receptors. Cell. Mol. Life Sci. 75, 1959–1971 (2018).OpenUrlCrossRef ↵ B. Obermeier et al., Matching of oligoclonal immunoglobulin transcriptomes and proteomes of cerebrospinal fluid in multiple sclerosis. Nat Med. 14, 688–693 (2008).OpenUrlCrossRefPubMed ↵ M. Cerina et al., Thalamic Kv 7 channels: Pharmacological properties and activity control during noxious signal processing. Br. J. Pharmacol. 172, 3126–3140 (2015).OpenUrl ↵ P. Blaesse et al., μ-Opioid receptor-mediated inhibition of Intercalated neurons and effect on synaptic transmission to the central amygdala. J. Neurosci. 35, 7317–7325 (2015). ↵ S. M. Brändle, “Analysis of oligoclonal band antibodies from patients with neurological diseases,” PhD thesis, Ludwig Maximilians University of Munich, Munich, Germany (2016). Log in using your username and password Username * Password * Log in Forgot your user name or password? Log in through your institution You may be able to gain access using your login credentials for your institution. Contact your library if you do not have a username and password. If your organization uses OpenAthens, you can log in using your OpenAthens username and password. To check if your institution is supported, please see this list. Contact your library for more details. Purchase access You may purchase access to this article. This will require you to create an account if you don't already have one. Subscribers, for more details, please visit our Subscriptions FAQ. Please click here to log into the PNAS submission website. Previous Next Share Sign up for the PNAS Highlights newsletter to get in-depth stories of science sent to your inbox twice a month: Sign up for Article Alerts Sign up ARTICLE CLASSIFICATIONS Biological SciencesImmunology and Inflammation JUMP TO SECTION YOU MAY ALSO BE INTERESTED IN Scientists should pursue a strategic approach to research, focusing on the accumulation of evidence via designed sequences of studies. Image credit: Dave Cutler (artist). Despite myriad challenges, clinicians see room for progress. Image credit: Shutterstock/David Tadevosian. Sneaky intracellular bacteria know when to defend themselves and multiply. Image credit: Camilla Ciolli Mattioli. Mara Reed and Michael Manga explore why Yellowstone's Steamboat Geyser resumed erupting in 2018. Listen Past PodcastsSubscribe A study demonstrates how two enzymes—MHETase and PETase—work synergistically to depolymerize the plastic pollutant PET. Image credit: Aaron McGeehan (artist). Similar Articles
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Expert Alert: Encephalitis prevention another reason to receive COVID-19 vaccine

Expert Alert: Encephalitis prevention another reason to receive COVID-19 vaccine | AntiNMDA | Scoop.it
Patients with COVID-19 are at risk for neurologic complications, including encephalitis, or inflammation of the brain."Encephalitis cases have been report...
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Distinguishing between two very similar pediatric brain conditions

Distinguishing between two very similar pediatric brain conditions | AntiNMDA | Scoop.it
Slight differences in clinical features can help physicians distinguish between two rare but similar forms of autoimmune brain inflammation in children, a new study by UT Southwestern scientists suggests.
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Relationship Between Serum NMDA Receptor Antibodies and Response to Antipsychotic Treatment in First-Episode Psychosis - UCL Discovery

Relationship Between Serum NMDA Receptor Antibodies and Response to Antipsychotic Treatment in First-Episode Psychosis - UCL Discovery | AntiNMDA | Scoop.it
UCL Discovery is UCL's open access repository, showcasing and providing access to UCL research outputs from all UCL disciplines.
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Treatment of Movement Disorder Emergencies in Autoimmune Encephalitis in the Neurosciences ICU

Treatment of Movement Disorder Emergencies in Autoimmune Encephalitis in the Neurosciences ICU | AntiNMDA | Scoop.it
Immune response against neuronal and glial cell surface and cytosolic antigens is an important cause of encephalitis. It may be triggered by activation of the immune system in response to an infection (para-infectious), cancer (paraneoplastic), or due to a patient's tendency toward autoimmunity.
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

A Rare Case of Wobbly, Psychotic Patient with Frozen Eyes - Anti-AMPA Receptor Encephalitis

A Rare Case of Wobbly, Psychotic Patient with Frozen Eyes - Anti-AMPA Receptor Encephalitis | AntiNMDA | Scoop.it
This is the first report of AMPAR associated encephalitis from India presenting with unique clinical features affecting both the CNS (central nervous system)--(psychosis, ataxia, cognition) and PNS--peripheral nervous system involvement (ptosis, restricted eye movements, bulbar disturbances).
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Autoimmune encephalitis: understanding prevalence and pathogenesis

Autoimmune encephalitis: understanding prevalence and pathogenesis | AntiNMDA | Scoop.it
Divyanshu Dubey, MBBS, Mayo Clinic, Rochester, MN, outlines recent epidemiological and biological findings in autoimmune encephalitis, a condition in which neuroinflammation causes various neurologic and/or psychiatric symptoms.
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Autoimmune encephalitis: proposed best practice recommendations for diagnosis and acute management | Journal of Neurology, Neurosurgery & Psychiatry

Introduction Autoimmune encephalitis (AE) comprises a group of non-infectious immune-mediated inflammatory disorders of the brain parenchyma often involving the cortical or deep grey matter with or without involvement of the white matter, meninges or the spinal cord.1–4 The original description of AE was based on paraneoplastic conditions related to antibodies against intracellular onconeuronal antigens such asANNA-1/anti-Hu.5 6 These ‘classical’ antibodies are non-pathogenic but represent markers of T-cell-mediated immunity against the neoplasm with secondary response against the nervous system. In recent years, an increasing number of antibodies targeting neuronal surface or synaptic antigens have been recognised such as N-MethylD-Aspartate Receptor (NMDAR)-antibody and Leucine-richglioma inactivated (LGI1)-antibody.1 Most of these surface antibodies have been shown to be likely pathogenic and are thought to mediate more immunotherapy-responsive forms of AE and have less association with tumours. Specific types of encephalitis can occur in the setting of antibodies against oligodendrocytes (eg, anti-myelin oligodendrocyte glycoprotein (MOG) brainstem encephalitis) or astrocytes (eg, anti-aquaporin-4 (AQP4) diencephalic encephalitis, anti-glial fibrillary acidic protein (GFAP) meningoencephalitis). In addition, some AE patients do not have any identifiable antibodies (seronegative) representing a disease category with novel, yet to be identified antibodies or T-cell mediated disease. Online supplemental appendix S1 contains a list of the commercially available neuronal autoantibodies (NAAs). Supplemental material Recent epidemiological studies suggest that AE is possibly as common as infectious encephalitis with an estimated prevalence rate of 13.7/100 000.7 The rapidly advancing knowledge of new antibodies and their associated syndromes has created a new and growing field of autoimmune neurology.8 However, advances from the laboratory bench have not been paralleled by advancement in clinical practice, leading to a large knowledge gap and many unanswered questions regarding the acute and long-term management of AE. The heterogeneity of AE presentation and findings on ancillary testing hinder large-scale clinical trials and limit the quality of evidence behind AE management. The objective of this paper is to evaluate available evidence for each step in AE management and provide expert opinion when evidence is lacking. Although the turnaround time of commercial NAAs panels may improve in the near future, currently these results are often unavailable at the time of early evaluation and management. Moreover, current commercial NAAs panels are inherently limited in their ability to diagnose AE, given the ever-growing numbers of antibodies identified and the likelihood of T-cell mediated pathogenesis in some cases. Consequently, clinicians have to approach AE initially as a clinical entity when deciding on investigations and treatment.1 Long-term management can then be modified according to the type of antibody identified, if any. Therefore, the aim of this paper is to emphasise the practical acute and long-term management of AE as a broad category rather than focusing on individual antibody syndromes. Another important goal is to represent the practice of experienced clinicians from different clinical and geographical backgrounds. Methods Core authors from the Autoimmune Encephalitis Alliance Clinicians Network (AEACN) developed the first draft of this paper (HA, JCP, SI, RCD, EPF, PG, AJ, YL, AR-G, IR, SJP and MJT). The AEACN is comprised of self-identified clinicians with interest and clinical expertise in AE management listed by the AE Alliance, a non-profit organisation founded by AE patients and families to establish a supportive community for patients and caregivers, enhance clinical collaboration, and facilitate AE scientific research. The AEACN includes a multidisciplinary international group of adult and paediatric neurologists, rheumatologists, psychiatrists, neuropsychologists and other specialists with real-life experience in AE management. The authors of the first draft reviewed available literature to compile existing evidence for every step in AE management. Where evidence was lacking or controversial, an electronic survey was distributed to all AEACN members to solicit individual responses. The survey questions were strategically planned to look at initial treatment, continued care and finally long-term management. After adding survey results to the manuscript, the updated version was circulated to all participating AEACN members for edits and further suggestions. Survey results The survey was distributed to 147 Clinical members. Sixty-eight (46%) members responded including the core authors. The most represented specialty/subspecialty of the respondents was neuroimmunology (66%), followed by general neurology (21%), paediatric neurology (16%), epilepsy (9%), behavioural/cognitive neurology (6%), hospital neurology-neurohospitalist (6%), neuromuscular neurology (6%), paediatric rheumatology (6%), neurocritical care (4%), psychiatry (4%), movement disorders (3%), general paediatrics (3%) and one specialist (1.5%) each of the following: autonomic disorders, adult rheumatology and paediatric critical care. Twenty-five members (37%) indicated more than one subspecialty. Clinicians from 17 countries participated including USA (69%), Brazil (4%), Canada (3%), China (3%), Spain (3%), Argentina, Australia, Indonesia, Israel, Italy, the Netherlands, the Philippines, Singapore, South Korea, Switzerland, Turkey and the UK (countries listed in a descending order based on the number of responders and alphabetically when the number of responders was equal). Of the total participating members, 88% practiced at academic tertiary referral centres and 76% were active in AE clinical research or scholarly publications. The participating members indicated personal clinical experience with an average of 7.3 AE subtypes (range 1–13 subtypes, median 8 subtypes). In total, 9% of the participating members were affiliated with reference neuroimmunology laboratories with NAAs testing capabilities. The results of individual survey questions are presented under the corresponding sections of AE management. The final draft was approved by all participating AEACN members after four rounds of revisions. The paper aimed to answer prespecified clinical questions as detailed below. Data availability statement The results of the survey are partially summarised in figure 1 and the detailed responses of all survey questions are published as online supplemental document 2. Supplemental material Figure 1 AEACN survey results for acute and bridging therapy. AE, autoimmune encephalitis; AEACN, Autoimmune Encephalitis Alliance Clinicians Network; IVMP, intravenous methylprednisolone; IVIg, intravenous Ig; PLEX, plasma exchange. Section 1: diagnosis of AE When to suspect AE clinically? A detailed history and examination is the first and most important step in AE diagnosis. The immune reaction in AE often results in acute or subacute presentation of a duration less than 3 months.1 Chronic presentations are only seen in some of these conditions, especially LGI1, Contactin-associatedprotein-like 2 (CASPR2), Dipeptidyl-peptidase-likeprotein 6 (DPPX) and Glutamicacid decarboxylase 65 (GAD65)-antibody encephalitis, and should otherwise raise suspicion of a neurodegenerative disease or other etiologies.9 Likewise, hyperacute presentations are also atypical and a vascular aetiology should be considered in those cases. A recurrent course may point towards an autoimmune aetiology but unlike the typical relapsing-remitting course of multiple sclerosis and systemic inflammatory disorders, AE relapses are rare and often result from insufficient treatment or rapid interruption of immunotherapy. A monophasic course is more common in idiopathic AE while a progressive course may be seen in some paraneoplastic syndromes especially paraneoplastic cerebellar degeneration, which tends to plateau after the cancer is treated. Patients with known cancer or those at increased cancer risk (smokers, the elderly, and patients with rapid unintentional weight loss) are prone to paraneoplastic AE, while patients with personal or family history of other autoimmune disorders are at increased risk of idiopathic AE.10 A preceding viral infection, fever or viral-like prodrome is common.11 AE may be triggered by herpes simplex virus (HSV) encephalitis or certain immune-modulating therapies such as TNFα inhibitors, and immune-checkpoint inhibitors (ICIs)—the latter can cause an accelerated form of paraneoplastic encephalitis in patients with advanced cancer.1 12 Table 1 shows practical classification concepts in AE. VIEW INLINE VIEW POPUP Table 1 Proposed classification concepts in autoimmune encephalitis The immune reaction in AE is usually diffuse, resulting in multifocal brain inflammation and occasionally additional involvement of the meninges, spinal cord and/or the peripheral nervous system.3 6 This diffuse inflammation may or may not be detectable on ancillary testing but it usually results in a polysyndromic presentation which is a clinical hallmark of AE. Although some antibodies have been linked to stereotypical symptoms (eg, oromandibular dyskinesia, cognitive/behavioural changes, and speech and autonomic dysfunction in NMDAR-antibody encephalitis, faciobrachial dystonic seizures in LGI1-antibody encephalitis, etc), there is significant symptom overlap between all antibodies and all forms of AE.1 11 Symptoms vary according to the anatomical localisation of inflammation and there are several clinical-anatomical syndrome categories in AE as summarised in table 2. VIEW INLINE VIEW POPUP Table 2 Anatomical-clinical syndromes of autoimmune encephalitis What investigations should be ordered when AE is suspected? After AE is suspected clinically, a detailed workup is needed to confirm the diagnosis and exclude competing possibilities like infective encephalitis or systemic/metabolic causes. In most cases, the workup starts with brain imaging and cerebrospinal fluid (CSF) analysis. The diagnostic algorithm follows the structure summarised in figure 2 and detailed below: Aim 1: confirming the presence of focal or multifocal brain abnormality suggestive of encephalitis Figure 2 Diagnostic algorithm for autoimmune encephalitis. *EEG can confirm focal or multifocal brain abnormality and rule out subclinical seizures. **In addition to neuronal autoantibodies, cerebrospinal fluid should be tested for infections, inflammatory markers (IgG index and oligoclonal bands), and in some cases cytology. ***In addition to neuronal autoantibodies, the differential diagnosis generated based on MRI results will guide what blood tests to send. ****In most cases, general neoplasm screening starts with CT then other screening modalities are added until a neoplasm is found or eventually ruled out. If the clinical picture is highly suggestive of a specific neoplasm, a targeted screening approach could be implemented (eg, starting with pelvic ultrasound if the clinical picture is suggestive of anti-NMDAR encephalitis). AE, autoimmune encephalitis; EEG, electroencephalogram; MRI WWO, MRI with or without contrast; PET, positron emission tomography. Brain MRI In addition to ruling out alternative diagnoses, standard Brain MRI with contrast can show changes consistent with one or more of the AE anatomical syndromes (table 1 and figure 3). According to the 2016 AE clinical criteria by Graus et al, the presence of bilateral limbic encephalitis is the only MRI finding sufficient to diagnose definite AE in the correct clinical setting (eg, negative CSF viral studies) even in absence of NAAs.1 All other MRI patterns (cortical/subcortical, striatal, diencephalic, brainstem, encephalomyelitis and meningoencephalitis) can support possible or probable AE unless the NAAs panel is positive for a clinically relevant antibody.1 2 Diffuse or patchy contrast enhancement suggestive of inflammation is seen in a few patients while intense enhancing lesions are unlikely in AE.3 9 Rare findings include focal or extensive demyelination, meningeal enhancement, and rarely cortical diffusion restriction (often related to secondary seizures). Brain MRI may also be normal. Patients with initially negative MRI may show changes suggestive of AE on repeat MRI a few days later. Gadolinium should be avoided during pregnancy. Table 3 shows the main differential diagnoses for each of the AE anatomical syndromes. VIEW INLINE VIEW POPUP Table 3 Differential diagnosis of autoimmune encephalitis anatomical syndromes and suggested additional testing Figure 3 Anatomical subtypes of autoimmune encephalitis. (A) Limbic encephalitis, (B) cortical/subcortical encephalitis, (C) striatal encephalitis, (D) diencephalic encephalitis, (E) brainstem encephalitis (arrow), (F) meningoencephalitis (arrow). Importantly, brain MRI can also help exclude alternative diagnoses such as acute stroke, neoplasm or Creutzfeldt-Jacob disease (CJD), although AE MRI changes can sometimes mimic some of these entities. Unilateral, and to a lesser extent bilateral, inflammation of the mesial and non-mesial temporal lobe as well as the orbitofrontal cortex on FLAIR or DWI sequences supports herpetic encephalitis over AE.13 Parenchymal haemorrhage on gradient echo sequence is more common in herpetic encephalitis than AE although this difference did not reach statistical significance in one underpowered study comparing the two types of encephalitis.14 In some related immune-mediated conditions, the diagnosis can be inferred from typical MRI patterns such as radial perivascular enhancement in autoimmune GFAP astrocytopathy and punctate brainstem/cerebellar enhancement in chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS).15 16 Electroencephalogram Electroencephalogram (EEG) is commonly performed in patients with suspected AE to exclude subclinical status epilepticus in encephalopathic patients or to monitor treatment response in patients with seizures. AE is a major cause of new onset refractory status epilepticus (NORSE), which can be convulsive or non-convulsive.17 EEG can also provide evidence of focal or multifocal brain abnormality when MRI is negative which would support encephalitis over metabolic encephalopathy.1 Findings suggestive of AE include focal slowing/seizures, lateralised periodic discharges and/or extreme delta brush, which is occasionally seen in NMDAR-antibody encephalitis.18 Frequent subclinical seizures are commonly identified in LGI1-antibody encephalitis but patients may also have a normal EEG including those with classical faciobrachial dystonic seizures (FBDS).19 20 Although a normal EEG does not exclude AE, it can support primary psychiatric disorders when investigating patients with isolated new psychiatric symptoms. EEG can also help differentiate AE from CJD. Brain fluorodeoxyglucose positron emission tomography In the event of a negative brain MRI and clinical uncertainty despite high suspicion of AE, obtaining a brain fluorodeoxyglucose positron emission tomography (FDG-PET) can confirm focal or multifocal brain abnormality in the correct clinical setting.21 It can also substitute for MRI when MRI is contraindicated. In case series, brain FDG-PET was more sensitive than MRI and may reveal brain abnormalities at an earlier stage of the disease.22 Bilateral temporal hypermetabolism (in seropositive or seronegative limbic encephalitis) and bilateral occipitoparietal hypometabolism (in NMDAR-antibody encephalitis) are among the most common patterns seen and may prove useful biomarkers for specific syndromes. Importantly, further studies are needed to better differentiate AE metabolic patterns from neurodegenerative and neuroinfectious syndromes. In addition, immunosuppressants, anaesthetics and antiseizure therapies, commonly administered to AE patients, can also alter cortical metabolism. Seizures can also cause hypermetabolic changes on FDG-PET. The lack of specificity and the limited availability of FDG-PET are barriers against the wide utilisation of this technique in AE diagnosis. Aim 2: confirming an autoimmune inflammatory etiology and excluding other possibilities Following assessment for focal or multifocal brain abnormality by MRI or other studies, additional investigations are indicated to confirm AE and exclude other possibilities. Testing can be guided by the clinical-anatomical syndrome to narrow down the scope of investigations as shown in table 3. CSF analysis This is the most important test in AE evaluation and is usually the second step in the workup after brain MRI. Regardless of MRI findings, all patients with suspected encephalitis require a lumbar puncture (LP) unless there is a significant contraindication (eg, risk of herniation on brain imaging). In some cases, inflammatory CSF may be the only abnormality found on initial testing serving as the sole indication for empiric immunotherapy after infection is excluded. If timely brain MRI is not possible due to patient agitation or lack of access, clinicians should proceed with LP after a screening head CT so as not to delay immunotherapy. CSF analysis should include cell count and differential, protein, glucose, CSF/serum glucose ratio, albumin quotient, IgG index and synthesis rate, oligoclonal bands, broad viral studies including HSV1/2 PCR and varicella zoster virus (VZV) PCR and IgG/IgM, bacterial/fungal cultures when appropriate, cytology, flow cytometry, NAAs panel (eg, Autoimmune encephalopathy/encephalitis panel, etc), and in some cases, prion disorder panel (preferably RTQuIC when available). Common CSF findings in AE include mild to moderate lymphocytic pleocytosis (commonly 20–200 cells but can be as high as 900 cells with some antibodies), hyperproteinorrachia, and in some cases, elevated IgG index and/or IgG synthesis rate and positive intrathecal oligoclonal bands (unmatched in the serum).1 23 These findings in the setting of negative infectious and cytological studies support an immune-mediated aetiology but would not differentiate AE from other immune-mediated conditions (eg, neurosarcoidosis) so clinical correlation is always needed. In many patients, testing NAAs in both CSF and serum is needed because CSF detection is more sensitive for some antibodies (eg, NMDAR and GFAP antibodies) while serum is more sensitive for other antibodies (eg, onconeuronal, LGI1, and AQP4 antibodies).1 If the clinical picture is highly suggestive of an antibody with a higher serum sensitivity (eg, FBDS suggestive of LGI1-antibody encephalitis), then it might be reasonable to avoid CSF testing in clinical situations where CSF sampling is challenging. Although symptomatology can guide which neuronal antibodies (or antibody panels) to test for in some patients, it may be most practical to send the most comprehensive panel especially in patients with less defined presentations. This is because there is a significant syndromic overlap between most of these antibodies and because more than one antibody can coexist in the same patient.24 Notably, routine CSF studies may be normal in some AE patients and this does not exclude the diagnosis when other parameters are consistent with AE; therefore, testing NAAs panels is recommended in case of high clinical suspicion even if the CSF is normal.25 Blood tests In addition to testing NAAs in the serum, several blood tests are often needed to exclude other competing etiologies. Test selection can be guided by the MRI anatomical pattern as shown in table 3 but some tests may be useful in case of negative MRI such as antithyroid antibodies, toxicology screen, ammonia, vitamin B1/B12 levels, HIV, inflammatory markers, antinuclear antibodies, extractable nuclear antigen antibodies, antiphospholipid and lupus anticoagulant antibodies, immunoglobulins and metabolic and hormonal panels when appropriate.1 Monitoring sodium level is important since hyponatraemia is common with certain AE subtypes such as LGI-1 antibody encephalitis.19 Blood samples should be collected prior to treatment with intravenous immunoglobulins or plasmapheresis to avoid false positive or false negative results. Brain biopsy Most AE cases with normal brain MRI or typical MRI patterns (limbic, striatal, etc) do not require a brain biopsy. Rarely, a brain biopsy may be needed for atypical or mass-like lesions to exclude neoplastic or other possibilities especially when all other investigations point away from autoimmunity.1 Pathological findings in AE are nonspecific and include T-cell and/or B-cell perivascular and parenchymal infiltrates along with secondary gliosis.26 Aim 3: screening for an associated neoplasm It is nearly impossible to predict whether AE is paraneoplastic or non-paraneoplastic based on symptoms as both AE subtypes present similarly. Therefore, cancer screening should be considered in most adult AE patients at time of presentation.24 If the patient has a known history of cancer typically associated with paraneoplastic syndromes then a paraneoplastic aetiology is presumed, and repeat cancer screen is indicated to identify recurrence or progression. In patients with cancer history not typically associated with paraneoplastic neurologic syndromes (eg, basal cell skin cancer, prostate cancer), repeat cancer screen may unmask a new different tumour. The most common neoplasms associated with AE include small cell lung cancer, thymic neoplasm, breast cancer, ovarian teratoma or carcinoma, testicular teratoma or seminoma, neuroblastoma and lymphoma.24 In some patients, the suspicion of associated neoplasm may be high based on certain demographic factors (eg, smoking history or advanced age) or typical clinical picture (NMDAR-antibody encephalitis associated with ovarian teratoma). Although some antibodies have stronger cancer association than others (eg, antibodies against intracellular antigens), the implicated antibody is usually unknown at the time of first presentation. The following screening modalities are available: CT chest, abdomen and pelvis Initial screening with CT of the chest, abdomen and pelvis with contrast is a reasonable approach given its lower cost compared with FDG-PET and since it provides more structural details of the neoplasm (if present) to guide biopsy and further surgical intervention if indicated. A major limitation of CT-based screening is its low sensitivity for early breast and testicular cancers.24 In addition, CT is not preferred in children and pregnant women; and pelvic CT is not preferred for women in childbearing age in general. Moreover, CT contrast dye may be contraindicated due to renal impairment or dye allergy. In these situations, additional or alternative means (eg, MRI) of cancer screening are required. It is to be noted, however, that CT iodine-based dye is relatively safer in pregnant women compared with MRI gadolinium-based dye. Mammogram and breast MRI Breast cancer is a common source of paraneoplastic syndromes in females, and a mammogram should be performed if the initial CT screen is negative.24 Patients with a strong family history of breast cancer and those who are not up to date with their regular mammograms are a special concern. If mammogram is negative but the suspicion of breast cancer is high, then breast MRI may improve sensitivity of cancer detection. Pelvic or testicular ultrasound or MRI Young and middle age adults with a typical clinical picture of NMDAR-antibody encephalitis should be specifically screened for teratoma by a transvaginal or transabdominal pelvic ultrasound (or testicular ultrasound in males).24 In female patients with ataxic presentation (suggestive of PCA1/Yo antibody), pelvic ultrasound can screen for ovarian carcinoma. Likewise, in males with ataxia and other brainstem symptoms (suggestive of Ma and Kelch-like Protein-11 Antibodies), testicular ultrasound may reveal the associated neoplasm.27 Pelvic MRI may be useful if ultrasound is equivocal. Extraovarian and extratesticular germ cell tumours may be detected on CT-based or MRI-based general cancer screening. Whole body FDG-PET scan Whole body FDG-PET can be more sensitive for early neoplasms when initial CT screen is negative or inconclusive and the suspicion of cancer is high (eg, smoker elderly patient, classic paraneoplastic presentation).24 It can also be used as the initial screening tool when there is a contraindication to high resolution CT or iodine contrast. Insurance coverage can be an obstacle and insurers should consider fewer restrictions on FDG-PET in AE patients given the high likelihood of a coexisting cancer in those patients. Section 2: acute treatment Intensive care unit needs The main indications for intensive care unit (ICU) admission in AE include refractory status epilepticus, severe dysautonomia and respiratory compromise (eg, from brainstem involvement, associated neuromuscular syndrome or medication-induced hypoventilation).28 It is important for ICU clinicians to distinguish central non-infectious fevers caused by the primary disease from infectious processes. Careful monitoring and management of blood pressure and heart rate fluctuations is critical in patients with severe dysautonomia. A temporary pacemaker may be needed in patients with severe dysrhythmia until the dysautonomia improves. Patients with severe hyponatraemia may require controlled slow correction of sodium levels to avoid central pontine myelinolysis. In most cases, hyponatraemia is related to inappropriate antidiuretic hormone secretion and fluid restriction is sufficient. In rare occasions with massive inflammation and brain oedema, intracranial pressure monitoring and management may be indicated. AE patients are often subject to high doses of sedation, antiseizure medications, and other symptomatic therapies so monitoring for drug toxicity in the ICU is imperative. Empiric antimicrobial treatment In many encephalitis patients, differentiating infectious from autoimmune aetiologies may be difficult prior to CSF analysis and therefore starting empiric antimicrobials with CNS coverage is always recommended until infection is excluded. The common practice is to start CNS doses of intravenous acyclovir and standard coverage for bacterial meningitis. Antibiotics and acyclovir can later be discontinued if CSF bacterial and HSV/VZV studies return negative. Acute immunotherapy Several retrospective studies have shown that early and aggressive immunotherapy is associated with better outcomes in AE patients.1 29 The 2016 AE clinical criteria emphasise the importance of starting immunotherapy once AE is highly suspected and infectious etiologies are excluded based on CSF results (cell-count, glucose, viral PCR, gram stain). It is impractical and potentially hazardous to delay immunotherapy until AE is confirmed by a positive antibody. There are no robust clinical trials comparing the different modalities of acute immunotherapy; therefore, the choice of the initial therapy may be based on anecdotal evidence and factors related to the specific syndromic presentation and comorbidities as shown in figure 4 and detailed below: Figure 4 Therapeutic algorithm for autoimmune encephalitis. *Relative contraindications to steroids include uncontrolled hypertension, uncontrolled diabetes, acute peptic ulcer and severe behavioural symptoms that worsen with corticosteroid therapy. **Steroid-responsive conditions include faciobrachial dystonic seizures suggestive of LGI1-antibody encephalitis, autoimmune encephalitis in the setting of immune checkpoint inhibitors, central demyelination, autoimmune GFAP astrocytopathy, chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids, and steroid-responsive encephalopathy associated with autoimmune thyroiditis. ***High thromboembolic risk includes patients with known or suspected cancer, smoking history, hypertension, diabetes, hyperlipidaemia and hypercoagulable states. Ab, antibody; AE, autoimmune encephalitis; Ag, antigen; IVMP, intravenous methylprednisolone; IVIg, intravenous Ig; IL-6: interleukin 6; NORSE, new-onset refractory status epilepticus; PLEX, plasma exchange. High-dose corticosteroids Empiric treatment with intravenous methylprednisolone at a dose of 1 g per day for 3–7 days is a common reasonable approach to achieve initial immunosuppressive and anti-inflammatory effect in AE patients.1 It is also the preferred approach in presentations known to be specifically corticosteroid-responsive namely demyelinating pattern on MRI (suggestive of AE overlap with demyelinating syndromes),30 or dotted or radial enhancement (suggestive of CLIPPERS or autoimmune GFAP astrocytopathy, respectively).15 16 Patients with FBDS suggestive of LGI1-antibody encephalitis may also show a dramatic response to corticosteroids.19 Patients with known or highly suspected paraneoplastic AE associated with classical onconeuronal antibodies are thought to have a primarily T-cell mediated inflammation making corticosteroids, theoretically, a preferred option for immunosuppression over intravenous IG or plasma exchange (PLEX). However, paraneoplastic conditions associated with classical onconeuronal antibodies are often resistant to immunosuppression and tend to respond best to cancer therapy. A notable exception are patients who develop accelerated paraneoplastic AE in the setting of ICI treatment. These patients may be particularly responsive to corticosteroids given their inhibitory effect on T-cell overactivity which is the pathogenic hallmark of ICI-associated immune adverse events; however, second-line therapies may also be needed in some cases.12 On our AEACN survey, 84% of responders chose corticosteroids alone (65%) or in combination with other agents (19%) for initial immunotherapy in patients with a general AE presentation. Likewise, 74% of responders chose corticosteroids for initial immunotherapy for patients presenting with FBDS suggestive of LGI1-antibody encephalitis, alone (58%) or in combination with other agents (16%). For NMDAR-antibody encephalitis, corticosteroids remained the most popular choice on the survey. However, the percentage was lower selected only by 63% of responders either alone (35%) or combined with other agents (28%) indicating a larger diversity among specialists when selecting first-line therapy in those patients. Similar diversity was present for treatment of known or highly suspected paraneoplastic AE; whereas corticosteroids remained the most popular choice, it was chosen by only 48.5% of responders, alone (29%) or combined with other agents (19%) (see online supplemental document S2). One theoretical disadvantage to corticosteroids in AE is their potential for causing initial worsening of behavioural/psychiatric symptoms hampering a timely evaluation of treatment response although in most cases, corticosteroids may actually improve these symptoms. The use of corticosteroids may also be difficult in patients with common comorbidities such as uncontrolled hypertension or diabetes. Some experts recommend avoiding corticosteroids in patients with known GAD65-antibody associated neurological syndromes for fear of inducing type-1 diabetes but this concern remains theoretical without confirmatory studies. In patients with atypical or mass-like lesions on brain MRI in whom primary CNS lymphoma is on the differential diagnosis, corticosteroids should be delayed so as not to interfere with pathology results if a biopsy is considered during hospitalisation. Similar precautions are advisable when systemic autoimmunity such as sarcoidosis is on the differential. Intravenous Ig Intravenous Ig (IVIg) at a dose of 2 g/kg over 2–5 days is a relatively easy-to-use and timely option for fast immunomodulation when corticosteroids are contraindicated or when the clinical picture is suggestive of or known to be related to antibody-mediated disease (eg, probable or definite NMDAR-antibody encephalitis).29 IVIg can be more readily available than PLEX in some centres and it does not require a central line. A recent randomised blinded study showed IVIg efficacy over placebo in controlling seizures in a small number of patients with LGI1-antibody and CASPR2-antibody AE.31 On our AEACN survey, IVIg was the most popular acute immunotherapy if corticosteroids are contraindicated chosen by 41% of responders. Also 40% of responders indicated choosing IVIg alone or in combination with corticosteroids and other immunotherapies for acute therapy if the clinical picture was suggestive of NMDAR-antibody encephalitis. A downside to IVIg is its association with increased thromboembolic risk. Therefore, IVIg should be used with caution in patients with known or suspected paraneoplastic AE or other risk factors for thrombosis (eg, heavy smokers and the elderly). In addition, the aetiology of paraneoplastic AE associated with antibodies against intracellular antigens is thought to be cell-mediated rather than antibody-mediated rendering the use of IVIg in this setting potentially ineffective. On our survey only 25% of responders indicated using IVIg in known or suspected paraneoplastic AE. The use of IVIg may also worsen coexisting hyponatraemia due to volume expansion, which may potentially predispose to brain oedema and worsening mental status.32 Plasma exchange PLEX (5–10 sessions every other day) is an effective option for acute immunomodulation when corticosteroids are contraindicated or ineffective. In a small retrospective study, patients with NMDAR-antibody encephalitis treated with both corticosteroids and PLEX had better improvement in the modified Rankin score than those treated with corticosteroids alone,33 which is similar to the results in other antibody-mediated conditions like NMOSD.34 PLEX may be particularly effective in AE cases with associated central demyelination or coexisting NMOSD. It provides a potentially faster immunomodulation in patients with severe or fulminant presentations. It has no known psychiatric side effects and does not increase the risk of thromboembolism except for line-related thrombosis. Major limitations include increased bleeding risk, volume shifts (which can be problematic in dysautonomic patients), and the need for central line placement (in some institutions) with its associated risks. In addition, it is less suitable for agitated patients. Combined first-line therapies If the initial clinical picture is severe (eg, NMDAR-antibody encephalitis, NORSE, severe dysautonomia), clinicians may consider using combined first-line therapies from the beginning despite the lack of high quality evidence to support this practice. On our AEACN survey, combination therapy was the second most popular choice after corticosteroids alone if the clinical picture was suggestive of NMDAR-antibody encephalitis chosen by 28% of responders, and for unspecified AE (19%). More commonly, combination therapy is done sequentially if there is no meaningful response to the initial agent (eg, adding IVIg and/or PLEX after completing corticosteroids). On the survey, 62% of responders chose adding a different first-line therapy if the initial agent was ineffective while 26% chose going directly to a second-line agent. Other options like adding a second round or prolonging the duration of the same first-line agent were less popular. Second line agents If there is no meaningful clinical or radiological response to optimised first-line therapy after 2–4 weeks, the addition of a second-line agent with both rapid and sustained immunosuppressive effects can improve the outcome.29 However, the exact definition and timing of treatment responsiveness is not well defined and some clinicians may anecdotally choose earlier initiation of second-line agents. Both rituximab and cyclophosphamide have been used as second-line agents for rescue therapy in AE with good results.29 Rituximab is less toxic than cyclophosphamide and therefore is preferentially considered by most clinicians although it may not be as effective for cell-mediated inflammation as in the case of antibodies against intracellular antigens. However, although rituximab acts mainly on B-cells, it indirectly suppresses T-cell activity by reducing B-cell drive to T-cells. In most newly diagnosed cases, it is hard to determine clinically whether AE is antibody or cell-mediated before the antibody results are available. Some clues may help the clinician come to a preliminary hypothesis regarding aetiology (eg, FBDS or typical NMDAR-antibody encephalitis presentation suggest antibody-mediated AE while patients with known or increased cancer risk are more likely to have cell-mediated AE). Based on these clues, clinicians may decide to use rituximab or cyclophosphamide as a second-line agent if antibody results are delayed or if there is no access to antibody testing. Common rituximab dosing regimens include 375 mg/m2 weekly for 4 weeks or two doses of 1000 mg 2 weeks apart. Common dosing regimen of cyclophosphamide include 600–1000 mg/m2. A few case series have shown response to proteasome inhibitors that block plasma-cell generation (bortezomib), interleukin (IL)-6 inhibition (tocilizumab), or low dose IL-2 in patients who did not respond quickly to conventional second-line agents.35–37 However, the evidence behind these non-conventional rescue therapies remains limited and more research is needed to confirm their effectiveness in refractory AE. A clinical trial of ocrelizumab (a humanised anti-CD20 monoclonal antibody with a similar mechanism of action to rituximab) is currently recruiting, and a clinical trial of bortezomib is underway (www.clinicaltrials.gov, accessed 13 April 2020). When a second-line agent is used in the acute setting, it also serves as a bridging therapy to prevent early relapses that might happen if immunosuppression is abruptly discontinued.38 Prognostication and clinical severity tools are being developed to help select patients who would benefit from conventional and non-conventional second-line agents such as the anti-NMDAR Encephalitis 1-year Functional Status score and the Clinical Assessment Scale in Autoimmune Encephalitis.39 40 On the AEACN survey, 50% of responders indicated they would consider adding a second-line agent in the acute setting only if there was no response to more than one first-line agent, 32% indicated adding a second-line agent if there was no response to one first-line agent, while only 15% indicated using a second-line agent in the acute setting on all patients regardless of the response to first-line therapy. As for the preferred second-line agent, 80% of responders chose rituximab while only 10% chose cyclophosphamide in a clinical scenario with unknown antibodies and no clinical clues for aetiology. Conclusion In this first part of the best practice recommendations, we covered the clinical presentation, diagnostic workup and acute management of AE guided by published studies and the results of the AEACN survey providing updated recommendations for management of patients with suspected AE. The second part will follow with a focus on bridging therapy, symptomatic treatment and maintenance immunotherapy. A discussion of the limitations will be presented at the end of the second part. A summary of the best practice recommendations for AE diagnosis and acute management is presented in box 1. Box 1 Best practice recommendations summary for acute management of autoimmune encephalitis (AE) Evaluate the likelihood of AE relative to the patient’s clinical picture. Perform brain MRI and/or EEG to look for focal or multifocal brain abnormality. Perform lumbar puncture to support inflammatory aetiology and rule out infective/neoplastic causes. Test oligoclonal bands, IgG index, IgG synthesis rate and neuronal autoantibodies in the cerebrospinal fluid (CSF). Send blood tests to rule out other potential causes guided by neuroanatomical and clinical data. Test neuronal autoantibodies in the serum. Consider brain FDG-PET when there is a high clinical suspicion of AE and other paraclinical studies are uninformative. Perform cancer screening with CT chest, abdomen, and pelvis with contrast in relevant cases (or MRI when CT is contraindicated or not preferred). If negative, consider further testing with mammogram/breast MRI, pelvic ultrasound, and/or whole body FDG-PET guided by the clinical presentation and each patient’s specific cancer risk factors. Once infection is ruled out based on basic CSF results (eg, number of cells) and if biopsy for primary CNS lymphoma or neurosarcoidosis is not a consideration, start acute immunotherapy with high dose corticosteroids (or IVIG or PLEX if steroids are not preferred or contraindicated). If there is no clinical, radiological or electrophysiological improvement by the end of the initial treatment cycle, add IVIG or PLEX. Consider IVIG first in agitated patients and in those with bleeding disorders. Consider PLEX first in patients with severe hyponatraemia, high thromboembolic (or cancer) risk, and if there is associated brain or spinal demyelination. Consider starting with a combination therapy of steroids/IVIG or steroids/PLEX from the beginning (as opposed to sequentially) in patients with severe initial presentation (eg, severe NMDAR-antibody presentation, new onset refractory status epilepticus, severe dysautonomia, etc). If there is no clinical or radiological improvement 2–4 weeks after completion of combined acute therapy, consider starting a second-line agent when the clinical suspicion is high and/or a clinically relevant antibody is present. Consider rituximab in known or highly suspected antibody-mediated autoimmunity (eg, NMDAR-antibody encephalitis) and consider cyclophosphamide in known or highly suspected cell-mediated autoimmunity (eg, classical paraneoplastic syndrome). If no clear objective or subjective evidence of improvement with conventional second-line therapies, consider novel approaches such as tocilizumab or bortezomib although there is only minimal evidence to support their use. Start bridging therapy with gradual oral prednisone taper or monthly intravenous Ig or intravenous methylprednisolone. Avoid steroid taper or implement a shorter taper in vague cases with poor response to initial immunosuppressive therapy or when immunosuppression may impose higher risks than benefits (eg, patients with cancer or active infection). Acknowledgments The authors would like to thank Kimberley de Haseth, Director of Programs at the Autoimmune Encephalitis Alliance for coordinating the communication between the AEACN members and for distributing the survey. References ↵Graus F, Titulaer MJ, Balu R, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 2016;15:391–404.doi:10.1016/S1474-4422(15)00401-9pmid:http://www.ncbi.nlm.nih.gov/pubmed/26906964OpenUrlCrossRefPubMed ↵Dalmau J, Graus F. Antibody-Mediated encephalitis. N Engl J Med 2018;378:840–51.doi:10.1056/NEJMra1708712pmid:http://www.ncbi.nlm.nih.gov/pubmed/29490181OpenUrlCrossRefPubMed ↵Heine J, Prüss H, Bartsch T, et al. Imaging of autoimmune encephalitis--Relevance for clinical practice and hippocampal function. Neuroscience 2015;309:68–83.doi:10.1016/j.neuroscience.2015.05.037pmid:http://www.ncbi.nlm.nih.gov/pubmed/26012492OpenUrlCrossRefPubMed ↵Singh TD, Fugate JE, Rabinstein AA. The spectrum of acute encephalitis: causes, management, and predictors of outcome. Neurology 2015;84:359–66.doi:10.1212/WNL.0000000000001190pmid:http://www.ncbi.nlm.nih.gov/pubmed/25540320OpenUrlCrossRefPubMed ↵Graus F, Elkon KB, Lloberes P, et al. Neuronal antinuclear antibody (anti-Hu) in paraneoplastic encephalomyelitis simulating acute polyneuritis. Acta Neurol Scand 1987;75:249–52.doi:10.1111/j.1600-0404.1987.tb07928.xpmid:http://www.ncbi.nlm.nih.gov/pubmed/3035860 ↵Lancaster E. Paraneoplastic disorders. Continuum 2017;23:1653–79.doi:10.1212/CON.0000000000000542pmid:http://www.ncbi.nlm.nih.gov/pubmed/29200116OpenUrlPubMed ↵Dubey D, Pittock SJ, Kelly CR, et al. Autoimmune encephalitis epidemiology and a comparison to infectious encephalitis. Ann Neurol 2018;83:166–77.doi:10.1002/ana.25131pmid:http://www.ncbi.nlm.nih.gov/pubmed/29293273OpenUrlCrossRefPubMed ↵López-Chiriboga AS, Clardy SL. Emerging subspecialties in neurology: autoimmune neurology. Neurology 2017;89:e129–33.doi:10.1212/WNL.0000000000004356pmid:http://www.ncbi.nlm.nih.gov/pubmed/28894037OpenUrlPubMed ↵Abboud H, Rossman I, Mealy MA, et al. Neuronal autoantibodies: differentiating clinically relevant and clinically irrelevant results. J Neurol 2017;264:2284–92.doi:10.1007/s00415-017-8627-4pmid:http://www.ncbi.nlm.nih.gov/pubmed/28975404OpenUrlPubMed ↵Mittal MK, Rabinstein AA, Hocker SE, et al. Autoimmune encephalitis in the ICU: analysis of phenotypes, serologic findings, and outcomes. Neurocrit Care 2016;24:240–50.doi:10.1007/s12028-015-0196-8pmid:http://www.ncbi.nlm.nih.gov/pubmed/26319044OpenUrlCrossRefPubMed ↵López-Chiriboga AS, Flanagan EP. Diagnostic and therapeutic approach to autoimmune neurologic disorders. Semin Neurol 2018;38:392–402.doi:10.1055/s-0038-1660819pmid:http://www.ncbi.nlm.nih.gov/pubmed/30011418OpenUrlPubMed ↵Kumar N, Abboud H. Iatrogenic CNS demyelination in the era of modern biologics. Mult Scler 2019;25:1079–85.doi:10.1177/1352458519828601pmid:http://www.ncbi.nlm.nih.gov/pubmed/30767720OpenUrlPubMed ↵Oyanguren B, Sánchez V, González FJ, et al. Limbic encephalitis: a clinical-radiological comparison between herpetic and autoimmune etiologies. Eur J Neurol 2013;20:1566–70.doi:10.1111/ene.12249pmid:http://www.ncbi.nlm.nih.gov/pubmed/23941332OpenUrlCrossRefPubMed ↵Chow FC, Glaser CA, Sheriff H, et al. Use of clinical and neuroimaging characteristics to distinguish temporal lobe herpes simplex encephalitis from its mimics. Clin Infect Dis 2015;60:1377–83.doi:10.1093/cid/civ051pmid:http://www.ncbi.nlm.nih.gov/pubmed/25637586OpenUrlCrossRefPubMed ↵Fang B, McKeon A, Hinson SR, et al. Autoimmune glial fibrillary acidic protein Astrocytopathy: a novel meningoencephalomyelitis. JAMA Neurol 2016;73:1297–307.doi:10.1001/jamaneurol.2016.2549pmid:http://www.ncbi.nlm.nih.gov/pubmed/27618707OpenUrlPubMed ↵Tobin WO, Guo Y, Krecke KN, et al. Diagnostic criteria for chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). Brain 2017;140:2415–25.doi:10.1093/brain/awx200pmid:http://www.ncbi.nlm.nih.gov/pubmed/29050399OpenUrlPubMed ↵Gaspard N, Foreman BP, Alvarez V, et al. New-Onset refractory status epilepticus: etiology, clinical features, and outcome. Neurology 2015;85:1604–13.doi:10.1212/WNL.0000000000001940pmid:http://www.ncbi.nlm.nih.gov/pubmed/26296517OpenUrlCrossRefPubMed ↵Steriade C, Moosa ANV, Hantus S, et al. Electroclinical features of seizures associated with autoimmune encephalitis. Seizure 2018;60:198–204.doi:10.1016/j.seizure.2018.06.021pmid:http://www.ncbi.nlm.nih.gov/pubmed/30031297OpenUrlPubMed ↵Irani SR, Michell AW, Lang B, et al. Faciobrachial dystonic seizures precede LGI1 antibody limbic encephalitis. Ann Neurol 2011;69:892–900.doi:10.1002/ana.22307pmid:http://www.ncbi.nlm.nih.gov/pubmed/21416487 ↵Aurangzeb S, Symmonds M, Knight RK, et al. Lgi1-Antibody encephalitis is characterised by frequent, multifocal clinical and subclinical seizures. Seizure 2017;50:14–17.doi:10.1016/j.seizure.2017.05.017pmid:http://www.ncbi.nlm.nih.gov/pubmed/28586706OpenUrlPubMed ↵Probasco JC, Solnes L, Nalluri A, et al. Abnormal brain metabolism on FDG-PET/CT is a common early finding in autoimmune encephalitis. Neurol Neuroimmunol Neuroinflamm 2017;4:e352. doi:10.1212/NXI.0000000000000352pmid:http://www.ncbi.nlm.nih.gov/pubmed/28567435 ↵Solnes LB, Jones KM, Rowe SP, et al. Diagnostic Value of 18F-FDG PET/CT Versus MRI in the Setting of Antibody-Specific Autoimmune Encephalitis. J Nucl Med 2017;58:1307–13.doi:10.2967/jnumed.116.184333pmid:http://www.ncbi.nlm.nih.gov/pubmed/28209905 ↵Blinder T, Lewerenz J. Cerebrospinal fluid findings in patients with autoimmune Encephalitis-A systematic analysis. Front Neurol 2019;10:804. doi:10.3389/fneur.2019.00804pmid:http://www.ncbi.nlm.nih.gov/pubmed/31404257OpenUrlCrossRefPubMed ↵Titulaer MJ, Soffietti R, Dalmau J, et al. Screening for tumours in paraneoplastic syndromes: report of an EFNS Task force. Eur J Neurol 2011;18:19–e3.doi:10.1111/j.1468-1331.2010.03220.xpmid:http://www.ncbi.nlm.nih.gov/pubmed/20880069OpenUrlCrossRefPubMed ↵Escudero D, Guasp M, Ariño H, et al. Antibody-Associated CNS syndromes without signs of inflammation in the elderly. Neurology 2017;89:1471–5.doi:10.1212/WNL.0000000000004541pmid:http://www.ncbi.nlm.nih.gov/pubmed/28878050OpenUrlPubMed ↵Maat P, de Beukelaar JW, Jansen C, et al. Pathologically confirmed autoimmune encephalitis in suspected Creutzfeldt-Jakob disease. Neurol Neuroimmunol Neuroinflamm 2015;2:e178. doi:10.1212/NXI.0000000000000178pmid:http://www.ncbi.nlm.nih.gov/pubmed/26601117 ↵Mandel-Brehm C, Dubey D, Kryzer TJ, et al. Kelch-Like protein 11 antibodies in Seminoma-Associated paraneoplastic encephalitis. N Engl J Med 2019;381:47–54.doi:10.1056/NEJMoa1816721pmid:http://www.ncbi.nlm.nih.gov/pubmed/31269365OpenUrlCrossRefPubMed ↵Harutyunyan G, Hauer L, Dünser MW, et al. Autoimmune encephalitis at the neurological intensive care unit: etiologies, reasons for admission and survival. Neurocrit Care 2017;27:82–9.doi:10.1007/s12028-016-0370-7pmid:http://www.ncbi.nlm.nih.gov/pubmed/28028790OpenUrlPubMed ↵Titulaer MJ, McCracken L, Gabilondo I, et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol 2013;12:157–65.doi:10.1016/S1474-4422(12)70310-1pmid:http://www.ncbi.nlm.nih.gov/pubmed/23290630 ↵Titulaer MJ, Höftberger R, Iizuka T, et al. Overlapping demyelinating syndromes and anti–N-methyl-D-aspartate receptor encephalitis. Ann Neurol 2014;75:411–28.doi:10.1002/ana.24117pmid:http://www.ncbi.nlm.nih.gov/pubmed/24700511OpenUrlCrossRefPubMed ↵Dubey D, Britton J, McKeon A, et al. Randomized placebo-controlled trial of intravenous immunoglobulin in autoimmune LGI1/CASPR2 epilepsy. Ann Neurol 2020;87:313–23.doi:10.1002/ana.25655pmid:http://www.ncbi.nlm.nih.gov/pubmed/31782181OpenUrlPubMed ↵Nguyen MK, Rastogi A, Kurtz I. True hyponatremia secondary to intravenous immunoglobulin. Clin Exp Nephrol 2006;10:124–6.doi:10.1007/s10157-006-0416-9pmid:http://www.ncbi.nlm.nih.gov/pubmed/16791398OpenUrlCrossRefPubMed ↵DeSena AD, Noland DK, Matevosyan K, et al. Intravenous methylprednisolone versus therapeutic plasma exchange for treatment of anti-N-methyl-D-aspartate receptor antibody encephalitis: a retrospective review. J Clin Apher 2015;30:212–6.doi:10.1002/jca.21363pmid:http://www.ncbi.nlm.nih.gov/pubmed/25664728OpenUrlPubMed ↵Abboud H, Petrak A, Mealy M, et al. Treatment of acute relapses in neuromyelitis optica: steroids alone versus steroids plus plasma exchange. Mult Scler 2016;22:185–92.doi:10.1177/1352458515581438pmid:http://www.ncbi.nlm.nih.gov/pubmed/25921047OpenUrlCrossRefPubMed ↵Scheibe F, Prüss H, Mengel AM, et al. Bortezomib for treatment of therapy-refractory anti-NMDA receptor encephalitis. Neurology 2017;88:366–70.doi:10.1212/WNL.0000000000003536pmid:http://www.ncbi.nlm.nih.gov/pubmed/28003505OpenUrlPubMed ↵Lee W-J, Lee S-T, Moon J, et al. Tocilizumab in autoimmune encephalitis refractory to rituximab: an institutional cohort study. Neurotherapeutics 2016;13:824–32.doi:10.1007/s13311-016-0442-6pmid:http://www.ncbi.nlm.nih.gov/pubmed/27215218OpenUrlPubMed ↵Lim J-A, Lee S-T, Moon J, et al. New feasible treatment for refractory autoimmune encephalitis: low-dose interleukin-2. J Neuroimmunol 2016;299:107–11.doi:10.1016/j.jneuroim.2016.09.001pmid:http://www.ncbi.nlm.nih.gov/pubmed/27725107OpenUrlPubMed ↵Nosadini M, Mohammad SS, Ramanathan S, et al. Immune therapy in autoimmune encephalitis: a systematic review. Expert Rev Neurother 2015;15:1391–419.doi:10.1586/14737175.2015.1115720pmid:http://www.ncbi.nlm.nih.gov/pubmed/26559389OpenUrlCrossRefPubMed ↵Balu R, McCracken L, Lancaster E, et al. A score that predicts 1-year functional status in patients with anti-NMDA receptor encephalitis. Neurology 2019;92:e244–52.doi:10.1212/WNL.0000000000006783pmid:http://www.ncbi.nlm.nih.gov/pubmed/30578370OpenUrlPubMed ↵Lim J-A, Lee S-T, Moon J, et al. Development of the clinical assessment scale in autoimmune encephalitis. Ann Neurol 2019;85:352–8.doi:10.1002/ana.25421pmid:http://www.ncbi.nlm.nih.gov/pubmed/30675918OpenUrlPubMed
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Nurse saved friend's life by diagnosing her with encephalitis when doctors couldn't | Metro News

Nurse saved friend's life by diagnosing her with encephalitis when doctors couldn't | Metro News | AntiNMDA | Scoop.it
A nurse at the Royal Liverpool Hospital helped save her friend's life when she suggested testing her for encephalitis.
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Cross-reactivity of a pathogenic autoantibody to a tumor antigen in GABA A receptor encephalitis

Cross-reactivity of a pathogenic autoantibody to a tumor antigen in GABA A receptor encephalitis | AntiNMDA | Scoop.it
Encephalitis associated with antibodies against the neuronal gamma-aminobutyric acid A receptor (GABA<sub>A</sub>-R) is a rare form of autoimmune encephalitis. The pathogenesis is still unknown but autoimmune mechanisms were surmised.
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

22 highlights from World Encephalitis Day 2021

22 highlights from World Encephalitis Day 2021 | AntiNMDA | Scoop.it
Here are 22 highlights from World Encephalitis Day on the 22nd February, 2021.
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

A Mind for Criminal Law–Automatism, Autoimmune Encephalitis & other Medical Conditions-Natasha Ellis

A Mind for Criminal Law–Automatism, Autoimmune Encephalitis & other Medical Conditions-Natasha Ellis | AntiNMDA | Scoop.it
Justice Bastarche defined automatism in R v Stone as “a state of impaired consciousness…in which an individual, though capable of action, has no voluntary control over that action”.The two categories of automatism that will be explored in this post are mental disorder automatism and non-mental disorder...
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Distinguishing between two very similar pediatric brain conditions: Identifying characteristics of acute disseminated encephalomyelitis and autoimmune encephalitis may lead to better treatments.

Distinguishing between two very similar pediatric brain conditions: Identifying characteristics of acute disseminated encephalomyelitis and autoimmune encephalitis may lead to better treatments. | AntiNMDA | Scoop.it
Slight differences in clinical features can help physicians distinguish between two rare but similar forms of autoimmune brain inflammation in children, a new study suggests. The findings could provide patients and their families with a better prognosis and the potential to target treatments...
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Expert Alert: Encephalitis prevention another reason to receive COVID-19 vaccine – Mayo Clinic News Network

Expert Alert: Encephalitis prevention another reason to receive COVID-19 vaccine – Mayo Clinic News Network | AntiNMDA | Scoop.it
Expert Alert: Encephalitis prevention another reason to receive COVID-19 vaccine...
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Q&A: Early diagnosis critical in treating encephalitis due to COVID-19, other causes

Feb. 22 marks World Encephalitis Day, a day of global awareness started by the Encephalitis Society for individuals &ldquo;who have been directly or indirectly affected by encephalitis,&rdquo; which now includes patients with COVID-19.Healio Neurology spoke with Omar K.
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Seizures and memory impairment induced by patient-derived anti-N-methyl-D-aspartate receptor antibodies in mice are attenuated by anakinra, an interleukin-1 receptor antagonist

Seizures and memory impairment induced by patient-derived anti-N-methyl-D-aspartate receptor antibodies in mice are attenuated by anakinra, an interleukin-1 receptor antagonist | AntiNMDA | Scoop.it
Our evidence supports a role for IL-1 in the pathogenesis of seizures in anti-NMDAR encephalitis. These data are consistent with therapeutic effects of anakinra in other severe autoimmune and inflammatory seizure syndromes.
No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Long-term Functional Outcomes and Relapse of Anti-NMDA Receptor Encephalitis | Neurology Neuroimmunology & Neuroinflammation

Long-term Functional Outcomes and Relapse of Anti-NMDA Receptor Encephalitis | Neurology Neuroimmunology & Neuroinflammation | AntiNMDA | Scoop.it
Nesrin Shaheens insight:

Great article!

No comment yet.
Scooped by Nesrin Shaheen
Scoop.it!

Anti-NMDA receptor encephalitis with phenytoin toxicity: A diagnostic dilemma and management challenge Kumar A, Kumar N, Kumar A, Ghosh S - Indian J Anaesth

Anti-NMDA receptor encephalitis with phenytoin toxicity: A diagnostic dilemma and management challenge Kumar A, Kumar N, Kumar A, Ghosh S - Indian J Anaesth | AntiNMDA | Scoop.it
Indian Journal of Anaesthesia, Official publication of Indian Society of Anaesthesiologists...
No comment yet.