Brain on Fire- Anti NMDA R Encephalitis

https://www.med.upenn.edu/autoimmuneneurology/nmdar-encephalitis.html

Anti-NMDA R Encephalitis

What is anti-NMDA Receptor Encephalitis?

Anti-NMDA receptor encephalitis is a neurologic disease first identified by Dr. Josep Dalmau and colleagues at the University of Pennsylvania in 2007. It is an autoimmune disease, where the body creates antibodies against the NMDA receptors in the brain. These antibodies disrupt normal brain signaling and cause brain swelling, or encephalitis. It can affect both men and women, however, is more common among women. It primarily affects the young, including children and young adults. Some patients also have a tumor associated with this disease; the most common type is an ovarian teratoma in women. The name of this disease describes an immune attack on the NMDA receptors and can be explained as follows:

? Anti- Autoimmune Response

? NMDA Receptor- against NMDA receptors in the brain

? Encephalitis- causing swelling and disruption in brain signaling

Signs & Symptoms

Anti-NMDA receptor encephalitis causes a wide range of symptoms varying in severity.  Patients typically start with less severe symptoms, and then rapidly progress to a condition requiring hospitalization. The list below includes the most common symptoms. Most patients with this disease exhibit nearly all of these symptoms; it is extremely uncommon for patients to have only one or two.

? Behavior (paranoia, hallucinations, aggression, etc.)

? Cognition [Draw a Clock test etc.] The Mental status tests will show significant impairment along with Psychotic SX] Glasgow Coma Scale score can be below 10.

? Memory Deficit

? Speech Disorder

? Loss of Consciousness

? Movement Disorder (rhythmic motions with arms or legs, abnormal movements with the face or mouth)

? Seizures

? Autonomic Dysfunction

Diagnosis

Anti-NMDA receptor encephalitis is often first identified through clinical symptoms. Diagnosis is confirmed through lab testing of cerebral spinal fluid (CSF) or blood serum. This testing is available at a variety of commercial labs, including the Hospital of the University of Pennsylvania (1-800-PENN LAB).

Treatment

Treatment of anti-NMDA receptor encephalitis can vary according to patient, but typically includes a combination of the following:

First Line Treatment:

? Tumor removal (if tumor is present)

? Steroids

? Plasma Exchange (plasmapheresis)

? Intravenous immunoglobulin (IVIG)

Second Line Treatment:

? CellCept

? Rituximab

? Cytoxan

Recovery

Recovery is slow and typically occurs in reverse of symptom onset. The most severe symptoms typically resolve first while the cognitive, behavioral, and memory problems take longer to resolve. Most patients will make a full recovery within two years of disease onset.  Predictors of positive outcomes include presence of a tumor, quick diagnosis, and aggressive treatment including second line therapies. 

Causes

Like most autoimmune diseases it is not known what exactly what causes anti-NMDAR encephalitis. There are likely multiple environmental and genetic triggers that make people more susceptible to this disease, something we hope to pinpoint with future research.

https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(19)30244-3/fulltext

Lancet- Neurology: Published: July 17, 2019DOI:https://doi.org/10.1016/S1474-4422(19)30244-3

An update on anti-NMDA receptor encephalitis for neurologists and psychiatrists: mechanisms and models

? Prof Josep Dalmau, PhD ,Thais Armangué, PhD, Jesús Planagumà, PhD, Marija Radosevic, PhD, Francesco Mannara, PhD, Frank Leypoldt, PhD, et al.

Dr. Dalmau is one who figured out the Diagnosis. Dr. Najjar at UPenn treated the Index Patient

The identification of anti-NMDA receptor (NMDAR) encephalitis about 12 years ago made it possible to recognize that some patients with rapidly progressive psychiatric symptoms or cognitive impairment, seizures, abnormal movements, or coma of unknown cause, had an autoimmune disease. 

In this disease, autoantibodies serve as a diagnostic marker and alter NMDAR-related synaptic transmission. At symptom onset, distinguishing the disease from a primary psychiatric disorder is challenging. The severity of symptoms often requires intensive care. Other than clinical assessment, no specific prognostic biomarkers exist. The disease is more prevalent in women (with a female to male ratio of around 8:2) and about 37% of patients are younger than 18 years at presentation of the disease. 

Tumors, usually ovarian teratoma, and herpes simplex encephalitis are known triggers of NMDAR autoimmunity. About 80% of patients improve with immunotherapy and, if needed, tumor removal, but the recovery is slow. 

Animal models have started to reveal the complexity of the underlying pathogenic mechanisms and will lead to novel treatments beyond immunotherapy. Future studies should aim at identifying prognostic biomarkers and treatments that accelerate recovery.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6081068/

Medicine (Baltimore). 2018 Aug; 97(31): e11325.

Published online 2018 Aug 3. doi: 10.1097/MD.0000000000011325 PMCID: PMC6081068 PMID: 30075499

Successful treatment of anti-NMDA receptor encephalitis with early teratoma removal and plasmapheresis

A case report.

Monica Gomes Ferreira, MD,a,b,? Victoria Lapresa Alcalde, MD,a,b María Helena García Sánchez, MD, PhD,a Lourdes Hernández Hernández, MD, PhD,a,b and María José Doyague Sánchez, MD, PhDa,b

Abstract

Rationale

This report describes a Successful treatment of anti-NMDA receptor encephalitis with early teratoma removal and plasmapheresis.

Patient Concerns

We present a 31-year-old Caucasian nulliparous patient who was admitted as an emergency with general illness status accompanied by holocranial cephalalgia and fever.

Diagnoses

The previous symptoms were followed by disorientation, persecutory delusion, incoherent language, and tonic-clonic seizure.

Interventions

The patient was admitted in the intensive care unit (ICU) with Glasgow score 7.

Outcomes

Most of complementary exams (brain CT, brain MRI, blood analysis, PCR for virus on CSF) were normal except CSF leukocytosis and hyperproteinorrhachia. An abdominopelvic ultrasound revealed a 5-cm solid-cystic tumor in the left adnexal region, suggestive of teratoma. At that stage, the possibility of autoimmune encephalitis was considered, and confirmed later.

Lessons

This disease can only be successfully treated with fast surgical intervention and an early implementation of immunosuppressive therapies. The optimal timing of initiation and duration of therapeutic plasma exchange necessary to achieve good outcomes in patients with NMDAR remains unknown. This case report intends to increase awareness about the importance of early surgical treatment and early implementation of this potentially life-saving therapy and of continuing the treatment until complete remission of symptoms.

https://www.youtube.com/watch?v=Ptj8JrqgcG4

Amanda had a rare, autoimmune disorder called Anti NMDA receptor encephalitis - but she didn't know it. 

Anti-NMDA receptor encephalitis occurs when antibodies in the body attack NMDA receptors, which are located in the brain. These NMDA receptors are responsible for judgement, perception of reality, human interaction, the formation and retrieval of memory, and the control of activities like breathing and swallowing. 

Symptoms of Anti-NMDA receptor encephalitis can often be misdiagnosed as other psychotic conditions, and in Amanda's case she was misdiagnosed several times. Amanda suffered from terrible headaches, paranoia and delusions. She went to multiple doctors to seek help. Others thought she was crazy. 

It wasn't until she came to UPenn that she was cured. Penn researchers pinpointed her rare disease and created a treatment that cured it. Learn more about neurology services at Penn: https://goo.gl/HOyHxp Meet the physician that treated Amanda, Eric Lancaster, MD: https://goo.gl/b3qMyG Follow Penn Medicine on Facebook: www.facebook.com/pennmed Tweet with us: www.twitter.com/pennmedicine

https://www.youtube.com/watch?v=5xT6BIFv-IE

Susannah Cahalan’s story diagnosed with Anti NMDR Encephalitis in 02 07 2013,

Brain on Fire. My Name is Susannah.

https://www.goodreads.com/book/show/13547180-brain-on-fire

An award-winning memoir and instant New York Times bestseller that goes far beyond its riveting medical mystery, Brain on Fire is the powerful account of one woman’s struggle to recapture her identity. Prof Dalmau figured out the Diagnosis. Dr. Najjar Treated her at UPenn.

When twenty-four-year-old Susannah Cahalan woke up alone in a hospital room, strapped to her bed and unable to move or speak, she had no memory of how she’d gotten there. Days earlier, she had been on the threshold of a new, adult life: at the beginning of her first serious relationship and a promising career at a major New York newspaper. Now she was labeled violent, psychotic, a flight risk. What happened?

In a swift and breathtaking narrative, Cahalan tells the astonishing true story of her descent into madness, her family’s inspiring faith in her, and the lifesaving diagnosis that nearly didn’t happen.  

Please read Susannah Cahalan's book."Brain on Fire" It is a powerful gutsy and very human story that is inspirational and uplifting. Susannah brings you all to the triumphal conclusion through very traumatizing and debilitating, demoralizing, marginalized and totally bewildering experiences. Please also look into Amanda’s Story. You may be able to save a person's life by helping to recognize and get the diagnosis right early and enhance the recovery.

Velandy Manohar, MD., Medical Director, Aware Recovery Care-CT[ARC] President, ARC In-home Addiction Treatment, PC Distinguished Life Fellow- Am. Psychiatric Assoc.