Brain on Fire: A disease almost undocumented in medical history

Joan Joe. 03/19/2021

Imagine being a journalist juggling several articles, conducting multiple interviews, learning intensely and more, just to have your life turned completely upside down in a matter of months.

Susannah Cahalan, a 24-year-old reporter for the New York Post, knows what it’s like to be in that situation. She started to experience numbness, paranoia, light sensitivity and abnormal behavior in 2009. Seizures, hallucinations, increasingly erratic actions and even catatonia started to plague her. Her symptoms alarmed her relatives and perplexed several doctors.

“An interesting case” is something you don’t want to be to your doctor. Cahalan had the misfortune of becoming a one-of-a-kind and perplexing case: she was gravely ill and rapidly deteriorating, but her MRIs, brain scans and blood tests were all fine. She took $1 million worth of blood tests and brain scans that were inconclusive.

Grandiosity, hysteria, fits of irrational anger, nonsensical utterances and flat catatonic-like effect were among the signs of the condition, which were mostly indistinguishable from one another throughout their early stages. There were also seizures with “blood and foam” spurting from Cahalan’s mouth, indicating a neurological condition rather than mental illness.

Cahalan was seen by Dr. Souhel Najjar, a Syrian-American neurologist, after a month in the hospital. He asked her to draw a clock on a piece of paper. She drew the circles and the numbers one to 12 all on the right-hand side of the clock, but the left-hand side was blank. It revealed that she had left-side spatial neglect and that the right side of her brain, which controls her left field of vision, was inflamed.

Najjar simply told her parents that her brain was on fire. This observation led to her getting diagnosed with anti-NMDA receptor encephalitis, a very rare autoimmune disease that is almost undocumented in the medical literature. Dr. Josep Dalmau and colleagues at the University of Pennsylvania first discovered anti-NMDA receptor encephalitis in 2007.

The disorder was portrayed in the 2016 Netflix film Brain on Fire in which Susannah Cahalan was played by Chloe Grace Moretz. This film was based on Susannah’s book called “Brain on Fire: My Month of Madness” after chronicling her experience in a 2009 New York Post report.

Anti-NMDAR encephalitis induces confusion, memory loss and seizures, which are often accompanied by altered consciousness and changes in blood pressure, heart rate and temperature, as portrayed in the film. The film’s graphic depictions of these symptoms – hallucinations, delusions and aggression – shocked audiences, but were true.

The entire event (in the hospital) lasted one month, but Susannah has no recollection of what happened to her, except for sporadic, almost hallucinatory flashbacks, such as being strapped to her hospital bed as a “flight risk.” Her only knowledge of what had happened to her and her behavior came from a journal kept by her father, mother and boyfriend when they were watching over her in the hospital. After her diagnosis, Susannah was quickly on the mend, and after several months, she was able to return to work.

Young women like Susannah are the majority of those who experience anti-NMDA receptor encephalitis. The average age is 20 years old. Since people’s behavioral changes can be very drastic, it’s not uncommon for them to be admitted to a psychiatric facility first. Physicians usually know the issue isn’t mental when neurological signs occur, such as seizures or a lack of responsiveness.

Nearly every neuron in the brain contains NMDA receptors. These receptors are necessary for the development of new memories in the hippocampus of humans and animals, and have been linked to several neurological and psychiatric disorders such as Alzheimer’s disease, schizophrenia and depression.

Antibodies are components of the immune system that protect the body from infection and illness. They respond with proteins in the body when they don’t function properly, resulting in an autoimmune disorder. Autoimmune encephalitis is a condition in which the body reacts to proteins in the brain. An assault on the NMDA receptor, one of the most important neurotransmitter receptors in the brain, prompts the adverse side effects that come with the condition. Intellectual changes, extreme memory loss, seizures and even death are all symptoms of the disorder.

Anti-NMDA receptor encephalitis manifests itself in a variety of ways, with varying degrees of severity. Patients usually begin with milder symptoms and quickly progress to a condition that necessitates hospitalization. Clinical signs are often used to diagnose anti-NMDA receptor encephalitis. The diagnosis is validated by analyzing the cerebral spinal fluid (CSF) or blood serum in the lab.

The medication for this condition varies by patient but usually involves a combination of first and second-line treatments. The first-line treatment consists of tumor removal (if present), steroids, plasma exchange (plasmapheresis) and intravenous immunoglobulin (IVIG). The second-line treatment is generally CellCept, Rituximab and Cytoxan.

Recovery is gradual and usually happens in the same order as the onset of symptoms. The most serious symptoms usually go away first, although cognitive, behavioral and memory issues take longer. Within two years of onset, the majority of patients will be completely recovered. The prompt diagnosis and aggressive treatment, including second-line therapies, are all predictors of positive outcomes.

Even if we do not know the exact cause of this disease, we can hope for significant advances in this field of study.

Cover Photo: (Netflix)