Brain on fire disease (A 7 point guide)

In this post we will explain what the strange condition called ” Brain on fire ” is, how it was discovered, how it occurs, its main symptoms and treatments.

Brain on fire disease

Not much is said about it and yet it is a life-threatening disease if not treated in time. The writer Susannah Cahalan reveals the anguish of this disease.

There are already new advances in the diagnosis and treatment of “brain on fire”, a life-threatening disease that was put on the scene thanks to the writer Susannah Cahalan, who revealed the anguish she suffered with this disease.

Recently a study has been published that reports on an animal model created to study this devastating disease for those who suffer from it.

“Brain on Fire” is the title of a successful autobiography that was brought to the big screen in 2017, which put this disease on the medical scene that, in the first instance, can be confused with epilepsy (due to the seizures it produces), with stress and even with burn out (a type of work stress and extreme state of exhaustion, whether physical, emotional or mental).

However, soon the doctors who treated Cahalan realized that they were facing another disease that could be fatal.

It must start by saying that it is an autoimmune disease triggered by an attack on one of the key neurotransmitters in the brain: the NMDA receptor.

From the outset, the disease is characterized by intellectual changes such as severe memory loss, confusion, altered state of mind, anxiety, mood swings, stress derived from lack of mental control, psychosis, hallucinations, seizures, and even death.

Encephalitis: autoimmune disease

When the best-seller and the film put this disease on the medical landscape, scientists witnessed how accurately Cahalan describes the symptoms of anti-NMDA antibody Encephalitis, as well as the process by which it was diagnosed.

In fact, she is a case among a few because in 2009 (only 3 before she became ill) the first cases were had and it is possible that many people have not been diagnosed as they should be.

Even Susannah herself had been told that she suffered from bipolar disorder, schizophrenia, and alcoholism (when she doesn’t drink alcohol).

Dr. Souhel Najjar, a Syrian-American neurologist from New York University, was in charge of her medical care and the first step in determining her disease was for Susannah to draw a clock, a test that is used in people who are beginning to suffer from dementia or Alzheimer’s.

There Dr. Najjar saw that Susannah put the numbers 1 to 12 together on the right side and confirmed that the right side of her brain (which regulates the left side of the body) was inflamed. He was the one who determined that Cahalan’s brain was “on fire.”

Progress on the disease

Just because it is a relatively new disease, scientists have just developed a kind of animal model to improve its diagnosis and treatment. The study, already published in the journal Science Translational Medicine, reports on an animal model created specifically to study this mysterious disease.

Scientists at the Vollum Institute, Oregon Health and Science University (OHSU) have claimed that this model is the way to develop the most atomic image possible of how the immune system attacks the NMDA receptor.

We are facing an autoimmune disease that must be attacked from the root: block this autoimmune reaction and try new strategies. “The goal is a cure that is specific to this disease,” says lead author Gary Westbrook, senior scientist at the Vollum Institute.

For this development, Brian Jones, a doctoral student in the OHSU neuroscience graduate program, and Westbrook worked hand-in-hand in the lab of co-author Eric Gouaux, senior scientist at Vollum and a Howard Hughes Medical Institute investigator, who published an insight three-dimensional NMDA receptor in the journal Nature.

Since NMDA receptors are present in almost all neurons in the brain, they are essential for learning and memory, and are also associated with Alzheimer’s, schizophrenia, and depression.

However, unlike other conditions, encephalitis arises unexpectedly and is influenced by several factors that can trigger it, when antibodies produced by the body’s own immune system attack NMDA receptors in the brain. “It’s a disease that we don’t know enough about,” admits Westbrook.

Mice to shine light on the topic                               

Gary Westbrook, Dixon Professor of Neurology at the OHSU School of Medicine, is confident that the animal model will be very helpful in determining the various sites on the NMDA receptor. Because it is important? “Because if we know the exact site, we could intervene earlier to abort the progression of the disease,” he says.

So they focused on modeling the disease by immunizing mice with the fully formed NMDA receptor. In almost 90% of the mice, certain signs that mimicked encephalitis developed, recognizing the early signs of the disease in order to have a more effective therapeutic approach against it.

What´s encephalitis?

Encephalitis corresponds to an inflammation of the brain tissue associated with neurological dysfunction; If, in addition to the brain, the meninges are inflamed, one speaks of meningo encephalitis, and one speaks of encephalopathy if there is dysfunction of the cerebral parenchyma but without inflammation.

This condition has different causes and forms of presentation, and can affect people of different age, gender and race. It is an important cause of neurological sequelae, especially in young people.

The causes of encephalitis can be divided into those of infectious, post-infectious, paraneoplastic and autoimmune origin, but approximately 60% of cases remain without a precise diagnosis.

Encephalitis or autoimmune encephalopathies are those caused by immunological factors such as antibodies or cellular immunity against antigens present in the brain parenchyma.

Depending on the type of immunity and antigen in question, autoimmune encephalitis can be subdivided into those produced by antibodies (AC) against cell surface antigens and those against intracytoplasmic antigens.

Symptoms of Anti-NMDA Receptor Encephalitis

Let’s go back to Susana Cahalan’s story, My brain on fire: a month of madness.

If you haven’t read the book, it tells the autobiographical story of a 24-year-old journalist who one day wakes up in the hospital with no memory of what happened in a month. During this period, Susana suffers from symptoms that include episodes of paranoia, violence and hallucinations.

In the first instance, she was diagnosed with an affective schizophrenic disorder. This means that the medical staff considered that Susana suffered from both schizophrenia and an affective disorder (anxiety or depression). Eventually, Ms. Cahalan was properly diagnosed with anti-NMDA receptor encephalitis.

The book ends with the recovery of the journalist, who had to undergo a biopsy and the corresponding treatment for her condition. But the positive ending to Susana Cahalan’s story is not entirely standard.

According to Dr. Souhel Najjar, who was the journalist’s treating physician, around 90% of the patients suffering from this condition since before 2009 were incorrectly diagnosed with a psychiatric disorder such as schizophrenia, bipolarity, OCD or depression.

Abnormal behavior is a characteristic symptom of anti-NMDA receptor encephalitis. This form of autoimmune encephalitis occurs mainly in women under 45 years of age who also tend to suffer (in 50% of cases) an ovarian teratoma (tumor made up of different types of tissue that is located in the ovaries).

One of the reasons that makes autoimmune encephalitis so difficult to diagnose is the extremely high range of symptoms it includes. Some of the most common are the following:

• Cognitive difficulties
• Reduced memory
• Convulsions
• Involuntary movements
• Reduced speech skills
• Behavioral changes
• Lack of inhibition
• Hallucinations
• Paranoid thoughts
• Severe anxiety
• Severe insomnia or sleep disorders
• Decreased consciousness (including catatonia, coma, or lack of response to stimuli)
• Weakness or tingling in the body
• Balance problems
• Changes in vision

About Anti-NMDA Receptor Encephalitis

N-methyl-D aspartate (NMDA) receptor antibody encephalitis is a serious and fatal but potentially reversible entity. It occurs more frequently in young women and in the clinical picture, the initial presentation of psychiatric symptoms is frequent; the subsequent manifestation of epileptic seizures reaches 80%.

In addition, involuntary movements stand out; and the alteration of consciousness with progression to a catatonic state; autonomic disorders are also characteristic.

N-methyl-D-Aspartate receptors (NMDAR) play an important role in synaptic transmission, neuronal plasticity, and long-term potentiation.

Antibodies against NMDAR decrease the surface density of receptors through antibody-mediated internalization, thereby decreasing NMDAR-mediated synaptic currents and creating an imbalance between the NMDA and AMPA pathways.

Immune responses are initiated by neoplastic cell proteins or following viral infections; these antigens are also expressed in neural cells and are therefore coincident.

The association of these antibodies to neoplasia ranges from 20 to 50% of cases, generally to ovarian teratoma. Immunotherapy with corticosteroids, immunoglobulin, plasmapheresis, or rituximab, constitutes the cornerstone of the treatment to be followed and, in paraneoplastic cases, tumor resection.

Likewise, the prolonged use of antiepileptic drugs may be necessary.

So, what happens in the brain of those affected?

A couple of years ago we were able to learn a little more about the history of patients suffering from this brain disease. This is the case of the journalist Susannah Cahalan who told in the book My Brain on Fire. Her mind became her greatest mystery and her hard life as a result of this pathology in a movie.

An ailment that gradually destroys the brain due to that attack that occurs on the NMDA receptor.

Surely you don’t know it, but it is one of the key neurotransmitter receptors within the functions that our brain has; especially in relation to learning and memory.

And it is that the immune system itself recognizes these receptors as if they were foreign bodies and they begin to be attacked by antibodies at the same time that brain inflammation occurs.

But before this “wreck” is greater, these patients begin to notice how they feel more tired, their hands and feet begin to fall asleep, lose concentration or have insomnia problems. In a second phase is when hallucinations or seizures begin and after these, the deterioration of cognitive function or heart rhythm disturbances.

In the most serious cases, as Susannah Cahalan herself explains, after a catatonic state in which these people lose the notion of their reality or the place where they are, some of them go into a coma and finally die.

The complication then lies in the fact that many of the first symptoms are confused with many other pathologies, which causes the diagnosis to be delayed. However, this disease can be potentially reversible if it is stopped in time.

And for this, for years, researchers such as those at the Vollum Institute, Oregon Health and Science University have made a discovery to block this harmful immune reaction, in addition to providing new therapeutic strategies not only to improve the quality of life of these patients but to, in the future, cure this disease.

FAQS: Brain on fire disease

What are the symptoms of anti NMDA receptor encephalitis?

Encephalitis due to antibodies against N-methyl-D-aspartate (NMDA) receptors is a potentially treatable entity, characterized by neuropsychiatric symptoms including seizures, altered consciousness, catatonia, and autonomic disorders.

What is the treatment for brain on fire?

Intravenous immunoglobulin (IVIG) therapy, plasmapheres and steroids were used to treat Cahalan.

Is brain on fire about mental illness?

There are neuropsychiatric symptoms, but it is an autoimmune disease.

What is anti NMDA receptor encephalitis?

It is an autoimmune disease, where the body creates antibodies against the NMDA receptors in the brain.

What triggers anti NMDA receptor encephalitis?

Anti-N-methyl D-aspartate (NMDA) receptor (anti-NMDAR) encephalitis, caused by immunoreactivity against the NMDA receptor 1 (NR1) subunit of the NMDA receptor.

In this post we explained what the strange condition called ” Brain on fire ” is, how it was discovered, how it occurs, its main symptoms and treatments.

If you have any questions or comments please let us know!

References

Symptoms – Autoimmune Encephalitis Alliance. (2018, May 31). Retrieved December 3, 2020, from Autoimmune Encephalitis Alliance website: https://aealliance.org/patient-support/symptoms/

‌FAQ – Autoimmune Encephalitis Alliance. (2019, March 13). Retrieved December 3, 2020, from Autoimmune Encephalitis Alliance website: https://aealliance.org/faq/#common-treatments

‌Titulaer, M. J., McCracken, L., Gabilondo, I., Armangué, T., Glaser, C., Iizuka, T., … Dalmau, J. (2013). Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. The Lancet Neurology, 12(2), 157–165. https://doi.org/10.1016/s1474-4422(12)70310-1

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