Susannah Cahalan, the journalist at the center of Brain on Fire, had anti-NMDA receptor encephalitis, a rare autoimmune disease in which the body’s immune system attacks a critical type of receptor in the brain. Her own antibodies were destroying the receptors her neurons needed to communicate, causing her to spiral from subtle personality changes into full psychosis, seizures, and near-catatonia over the course of several weeks. The disease had only been identified two years before her diagnosis, in 2007, by Dr. Josep Dalmau at the University of Pennsylvania.
How the Disease Attacks the Brain
NMDA receptors sit on the surface of neurons and play a central role in learning, memory, and synaptic signaling. In anti-NMDA receptor encephalitis, the immune system produces antibodies that latch onto these receptors and cause them to be pulled inside the cell, effectively removing them from service. The antibodies don’t damage other receptors or channels nearby. They specifically strip away the NMDA receptors, reducing the brain’s ability to process signals at its synapses.
When NMDA receptor activity drops, the symptoms closely mimic schizophrenia. That’s not a coincidence. Reduced NMDA receptor function is one of the leading biological models for how schizophrenia works. The difference is that in anti-NMDA receptor encephalitis, the cause is identifiable antibodies, and the process can be stopped with treatment. Left unchecked, the loss of receptors worsens, leading to seizures, movement disorders, and eventually autonomic instability where the brain begins losing control of basic functions like breathing and heart rate.
Susannah’s Symptoms, Step by Step
Cahalan’s illness followed a pattern that is now recognized as typical for this disease: it starts looking psychiatric and gradually becomes neurological. Over several weeks, her personality shifted. She developed paranoia, emotional instability, irrational jealousy, and even the belief that she could sense other people’s thoughts. She became increasingly erratic at work and withdrew from friends and colleagues. To the people around her, and to the doctors she initially saw, it looked like a psychiatric breakdown.
Then came the seizures. This was the turning point that moved her case from a psychiatrist’s office into a neurological workup. She was admitted to NYU Langone Medical Center, where her condition continued to deteriorate. She experienced hallucinations, periods of unresponsiveness, and abnormal involuntary movements. At her worst, she was barely recognizable as herself, cycling between agitation and near-catatonia.
One pivotal moment in the book involves a simple clock-drawing test. When asked to draw a clock face, Susannah crammed all twelve numbers onto the right side of the circle. This kind of error reveals dysfunction in the brain’s right hemisphere, specifically problems with spatial awareness and executive function. It was a concrete, visible sign that her brain was inflamed, not just producing psychiatric symptoms, and it helped steer her medical team toward the correct diagnosis.
Why It Took So Long to Diagnose
Anti-NMDA receptor encephalitis is frequently mistaken for schizophrenia or another psychiatric disorder, and the reason is straightforward: the initial symptoms are nearly identical. Psychiatric presentations, including hallucinations, delusions, agitation, and disordered thinking, are the most common first sign of this disease, appearing in 68 to 80 percent of cases. Standard brain imaging and routine lab work can come back normal in the early stages, which reinforces the psychiatric misdiagnosis. Patients may even respond temporarily to antipsychotic medications, further muddying the picture.
In one documented case, a patient carried a schizophrenia diagnosis for seven years before anti-NMDA receptor encephalitis was finally identified. Throughout those years, clinical exams, lab work, and neuroimaging had all seemed to support the schizophrenia diagnosis. The only way to confirm the autoimmune disease is to test for specific antibodies in the cerebrospinal fluid, obtained through a spinal tap. Standard psychiatric evaluations don’t include this test. Red flags that should prompt further investigation include disorientation, loss of consciousness, cognitive decline, involuntary movements, and rapid deterioration, even in someone with a prior psychiatric history.
Cahalan was fortunate that her neurological symptoms emerged clearly enough for her team at NYU to piece together the full picture. After weeks of worsening, they identified the anti-NMDA receptor antibodies and arrived at the correct diagnosis.
Treatment and Recovery
Treatment for anti-NMDA receptor encephalitis focuses on suppressing the immune system to stop it from producing the destructive antibodies. First-line approaches typically involve high-dose steroids, intravenous immunoglobulin (pooled antibodies from donors that help reset the immune response), and plasmapheresis, a process that filters the harmful antibodies directly out of the blood. If the disease is triggered by a tumor, most commonly an ovarian teratoma in young women, removing the tumor is a critical part of treatment.
Recovery is slow. Even after the immune attack is halted, the brain needs time to rebuild its receptor populations and restore normal signaling. Cahalan’s recovery took months, and she has described lingering cognitive effects, including gaps in memory from the period of her illness. Many patients experience a similar trajectory: gradual improvement over weeks to months, with some reporting subtle long-term changes in memory or processing speed. The earlier the disease is caught and treated, the better the outcome tends to be.
A Rare Disease That Changed Diagnosis
Anti-NMDA receptor encephalitis affects an estimated 1.5 people per million per year, making it genuinely rare. But since its identification in 2007, awareness has grown substantially, in large part because of Cahalan’s book and the 2016 film adaptation. Before the disease had a name, patients with these symptoms were likely institutionalized with psychiatric diagnoses or, in earlier centuries, might have been thought to be possessed. Cahalan herself has noted that her case could easily have gone undiagnosed if not for the specific expertise of the team treating her.
Her story has had a measurable effect on medical practice. Neurologists and psychiatrists are now more likely to consider autoimmune encephalitis in patients who present with sudden-onset psychosis, particularly when seizures or movement abnormalities follow. Testing for NMDA receptor antibodies has become more accessible, and the condition is now included in differential diagnoses where it once would not have been considered.