AntiNMDA

Circulating and cerebrospinal fluid (CSF) neurofilament light chain (NfL) levels represent a reliable indicator of disease activity and axonal damage in different neuroinflammatory conditions....

The aim of this study was to test whether autoantibodies against neurologic surface Ags are found in nonneurologic autoimmune diseases, indicating a broader loss of tolerance. Patient and matched healthy donor (HD) sera were derived from four large cohorts: 1) rheumatoid arthritis (RA) ( n = 194,...

Small questions don’t hold much appeal for Drs. Samuel Pleasure and Michael Wilson, Department of Neurology, and Joseph DeRisi, Department of Biochemistry and Biophysics. The talented trio is much more interested in tackling the really big problems, like getting to the root of the mysterious and sometimes deadly illnesses that puzzle even the most seasoned clinicians. Perhaps it’s no surprise that Drs. DeRisi, Pleasure, and Wilson’s latest project is especially ambitious. Together, they aim to develop a single test to diagnose any form of autoimmune encephalitis – a category of illness characterized by brain inflammation that is notoriously difficult to detect. The first-line test could be integrated into hospitals around the country, helping clinicians garner a diagnosis within 24 to 48 hours. The foundation for this work: “Along with other colleagues at UCSF, we’ve collected samples from hundreds of patients with mysterious causes of brain inflammation. Using a sequencing test developed by the team, we can now identify the singular cause of any infection – viral, bacterial, parasitic, or fungal. This development has led to lifesaving diagnoses for patients.” Michael Wilson Some patients remain a mystery: “Three or four times a month, we get a patient who has something that absolutely no one understands. Many of these patients are on a multitude of anti-infective drugs – antivirals, antibacterials – really everything but the kitchen sink. They come to us because they have nowhere else to turn.” Samuel Pleasure A tool to change it all: “What we don’t have is a tool that lets us say, ‘Well, it’s not infectious, it’s clearly autoimmune, and it’s B-cell driven’ or ‘It’s T-cell driven.’ A diagnostic test could be used in the clinic to guide a patient down one treatment path or another. If you know what you’re dealing with, you can make smart clinical decisions more quickly and ensure better outcomes for patients.” Samuel Pleasure How the test might work: “We would use sequencing and antibodies from the patients’ cerebrospinal fluid to search for gene expression patterns and antibody reactivity that would help categorize whether the patient is suffering from an infectious or autoimmune process.” Samuel Pleasure Why philanthropy matters: “It makes our work go at a much faster pace, and it obviates the lengthy – and sometimes completely unnecessary – cycle of grant applications and review. This kind of work is risky, but its impact is potentially huge.” Joseph DeRisi Why do this work at UCSF: We have a unique structure here that really blends basic sciences and clinical science. The departmental labels don’t mean much here, and the artificial barriers that traditional departmental structures create are absent. We’re also all physically close. There are three or four departments housed in my work neighborhood alone.” Joseph DeRisi

Dr. Luca Bartolini discusses autoimmune encephalitis and the role of antibody testing based on a Practice Current survey run between November 2017 and May 2018....

Case Reports in Neurological Medicine is a peer-reviewed, Open Access journal that publishes case reports and case series focusing on diseases of the nervous system, as well as abnormal neurological function.

Significant immunological alterations have been observed in women with first-onset affective psychosis during the postpartum period. Recent studies have highlighted the possibility that a subset of patients with first-onset severe psychiatric episodes ...

(The Lancet Psychiatry) – N-methyl-D-aspartate receptor (NMDAR)-antibody encephalitis is a neuropsychiatric disorder1, 2 that is caused by antibodies against the NR1 subunit of the NMDA receptor. Many patients with NMDAR-antibody encephalitis are...

Meet our Founding directors: Dr. H. Peery, Dr. G. Day, Dr. W. Foster and Ms. N. Shaheen.

The Foundation would like to thank all those neurology and psychiatry trainees who applied for the Foundation’s Travel award to attend the Symposium titled Autoimmune ...Read More...

A fifth case of limbic encephalitis associated with GAD antibodies and HHV-6 infection has been reported, this time in an immunocompetent woman with chromosomally integrated HHV-6, epilepsy, and psychosis. The patient’s condition improved (with a drop in GAD antibody titers and stabilization of psychotic symptoms) in response to three weeks of antiviral therapy but relapsed when antiviral therapy was withdrawn. Previously, the same neuropathology group in Germany reported two GAD-antibody-positive limbic encephalitis patients with HHV-6 DNA detected in surgically removed hippocampal tissue (Niehusmann 2010). Another publication reported two patients who had HHV-6-associated limbic encephalitis, autoimmune thyroid disease, and elevated antibodies to GAD (Mata 2008). GAD antibodies occur in a number of neurological disorders, and when the antibodies are extremely high, they can cause Stiff Person Syndrome. High level GAD antibodies define a relevant group of patients with chronic, nonremitting, and nonparaneoplastic limbic encephalitis (Malter 2010). At low levels, these antibodies are a predictive factor for type 1 diabetes. The authors note that antibodies against NMDAR, the surface protein N-methyl-D-aspartate receptor, have been identified as a cause of encephalopathy post HSV-1 encephalitis, and speculate that HHV-6 may trigger a similar cascade. They recommend further study to determine the frequency of simultaneous active HHV-6 infection and GAD65 antibodies. Of interest, a 1998 report identified GAD65 antibody stimulation in response to the HHV-6 U2 gene, via mimicry (Bach 1998). HHV-6 reactivation has been linked to many of the conditions associated with GAD antibodies. For example, HHV-6 reactivation has been found in cases of  fulminant type 1 diabetes after drug induced hypersensitivity syndrome (DIHS). In one series, HHV-6 reactivation was linked to 11 cases of fulminant type 1 diabetes (Onuma 2012). Two other cases of drug hypersensitivity and type 1 diabetes were reported by Taiwanese investigators in association with DRESS (Chiou 2006). Immunohistochemistry of brain tissue from this case showed T-lymphocytic infiltrates, a moderate activation of microglia, and moderate reactive astrogliosis. Anti-neuronal antibodies binding to pyramidal cells of the hippocampus and cerebellar Purkinje cells within the serum and CSF were identified using an indirect immunohistochemistry approach. The study was led by neuropathologist Pitt Niehusmann, MD from University Hospital Oslo, Norway and Albert Becker, MD from the Translational Epilepsy Research Section at the University of Bonn, Germany. For more information, read the full paper (Niehusmann 2016).

Twelve months ago, young Perth woman Ariana Pila spent most of her days in a comatose state, unable to eat, walk or talk. Today, the 21-year-old is making plans to walk the Great Wall of China, as well as study and work, thanks to an astonishing recovery from a rare autoimmune disease. She has got rid of her wheelchair, feeding tube and tracheostomy tube. With the help of therapists and her stubbornly determined personality, she has learned to sit, stand, walk and climb the stairs to her bedroom at home — and now she wants to take up jogging. "She always says 'I can't do it', but once she makes that first step past that word 'can't' and that fear, then all confidence comes in and she just smashes it," her mother, Kirstine Bruce, said. Struck down in her teens Five years ago, a 16-year-old Ms Pila collapsed in a fast food restaurant with anti-NMDA receptor encephalitis, a disease causing brain inflammation and psychiatric symptoms. Doctors held little hope she would ever regain any of her cognitive or physical abilities. "She was in a severely vegetative state," Ms Bruce said. "Thrashing. Her body was thrashing about the bed for the majority of the time. "High temps, high blood pressure, just absolutely everything." After being discharged from hospital, Ms Pila was forced to live in an aged care facility where she had little physiotherapy and spent her days watching television. Her mother saw occasional signs of a spark in her daughter and agitated for a different course of treatment for her, but it was a struggle. "We couldn't get any help for her," she said. "Because she was so severely vegetative, everyone was fobbing her off, saying, 'No, there's nothing we can do, she's got to fit a certain criteria'. "Everyone wrote her off." Now, after five months of intensive therapy at Perth disability services organisation Rocky Bay, as well as Fiona Stanley Hospital, Ms Pila has broken down physical barrier after physical barrier. "They doubted me that I was going to walk," she said. "They even thought that I wasn't ever going to wake up." Rare disease began with headaches Anti-NMDA receptor encephalitis was only identified as a condition in 2007, and it is understood only a few thousand people have been diagnosed with it worldwide. It affects the receptors in the brain which control, among other things, memory function. In Ms Pila's case, the disease has been linked to a benign teratoma tumour on her left ovary. Ms Bruce said her daughter was lucky to be diagnosed by her neurologist because many in her situation were incorrectly treated for mental health disorders like schizophrenia. Some neurologists believed many more people could have the disease but had been misdiagnosed. For Ms Pila, the onset of her disease began with headaches at age 13. She began to act strangely — "like bipolar, schizophrenic behaviours," Ms Bruce said — and then suffered memory loss. In April 2013, she deteriorated rapidly. After collapsing in the fast-food restaurant, she was taken to hospital and lost her ability to talk three days later. Five lost years Five years to the day later, Ms Pila began to speak again. Her first words were, "Hey Mama". But there were reminders of Ms Pila's lost teenage years, like the hole in her throat where her tracheostomy tube was inserted and the big chunks of her life missing from her memory. When she first began to wake from her comatose state about a year ago, she thought it was still 2012 and was shocked that her siblings looked so different. "She remembers everything from birth to 15 and then nothing from 16 to 21," Ms Bruce said. "She missed her formative years." But Ms Pila has big plans to fill in the gaps, starting with her first music concert next month. "She wants to work, she wants to study, she wants to go back home to New Zealand and we're going to do the Great Wall of China in 2020, that's what we're working towards," Ms Bruce said Ms Pila said she was proud of what she had achieved with the support of her family and therapy team. Her physiotherapist Jocelyn MacRae said the biggest factors behind Ms Pila's recovery were her family support and sheer determination. "As much as she says 'I can't' sometimes, she just breaks that barrier down and still gives it a go," she said. "There's never been a gym session where she hasn't given it a go or worked hard at it."

Objective Seizures develop in 80% of patients with anti–N‐methyl‐d‐aspartate receptor (NMDAR) encephalitis, and these represent a major cause of morbidity and mortality. Anti‐NMDAR antibodies have been linked to memory loss in encephalitis; however, their role in seizures has not been established. We determined whether anti‐NMDAR antibodies from autoimmune encephalitis patients are pathogenic for seizures. Methods We performed continuous intracerebroventricular infusion of cerebrospinal fluid (CSF) or purified immunoglobulin (IgG) from the CSF of patients with anti‐NMDAR encephalitis or polyclonal rabbit anti‐NMDAR IgG, in male C57BL/6 mice. Seizure status during a 2‐week treatment was assessed with video‐electroencephalography. We assessed memory, anxiety‐related behavior, and motor function at the end of treatment and assessed the extent of neuronal damage and gliosis in the CA1 region of hippocampus. We also performed whole‐cell patch recordings from the CA1 pyramidal neurons in hippocampal slices of mice with seizures. Results Prolonged exposure to rabbit anti‐NMDAR IgG, patient CSF, or human IgG purified from the CSF of patients with encephalitis induced seizures in 33 of 36 mice. The median number of seizures recorded in 2 weeks was 13, 39, and 35 per mouse in these groups, respectively. We observed only 18 brief nonconvulsive seizures in 11 of 29 control mice (median seizure count of 0) infused with vehicle (n = 4), normal CSF obtained from patients with noninflammatory central nervous system (CNS) conditions (n = 12), polyclonal rabbit IgG (n = 7), albumin (n = 3), and normal human IgG (n = 3). We did not observe memory deficits, anxiety‐related behavior, or motor impairment measured at 2 weeks in animals treated with CSF from affected patients or rabbit IgG. Furthermore, there was no evidence of hippocampal cell loss or astrocyte proliferation in the same mice. Significance Our findings indicate that autoantibodies can induce seizures in anti‐NMDAR encephalitis and offer a model for testing novel therapies for refractory autoimmune seizures.

We are Anti NMDA Receptor Encephalitis! | We are Anti NMDA Receptor Encephalitis!From...

Encephalitis is swelling and inflammation of the brain, which can be caused by infectious or autoimmune aetiologies.Up to 18.5% to 40.4% of patients were reported to develop status epilepticus (SE) d...

Scientists are now recognizing that a host of external stimuli can disrupt the normal crosstalk between the brain and the immune system...

Anti-N-methyl-D-aspartate receptor encephalitis mimics neuroleptic malignant syndrome: case report and literature review...

A fundraiser has been launched to help bring the body of an Edinburgh man who died in a foreign hospital back home to his heartbroken mother.

After the recent description of biphasic disease with herpes simplex virus (HSV) encephalitis
followed by anti-N-methyl-d-aspartate receptor encephalitis (anti-NMDARE), anti-NMDARE
preceded by non-HSV central nervous system (CNS) infection has been more rarely reported.

Ann Neurol. 2019 Jan 24. doi: 10.1002/ana.25421.[Epub ahead of print]...

Seizures and movement disorders are very common in anti-NMDA receptor encephalitis, as well as other forms of autoimmune encephalitis (AE) and researchers have undertaken to ...Read More...

Cureus. 2018 Oct 31;10(10):e3527. doi: 10.7759/cureus.3527.

Your first place to look. The leading information source for clinical neurology.

The family of a six-year-old Laval, Que., girl says the high-fat diet they feed her loaded with mayonnaise, avocados, and cream is helping to keep her epilepsy at bay.

Anti leucine-rich glioma inactivated 1 (LGI1) encephalitis is a rare autoimmune encephalitis (AE), characterized by acute or subacute cognitive impairment, faciobrachial dystonic seizures, psychiatric disturbances and hyponatremia.