Answer: Susannah Calahan is a patient who had anti-NMDA receptor encephalitis.
Susannah Cahalan is an American journalist who developed a case of the rare brain condition anti-NMDA receptor encephalitis. Through clinical reports of her disorder and her self-report account described in her autobiographical book, Brain on Fire: My Month of Madness, we have learned much about the clinical presentation and symptoms of this rare disease.
As a young journalist working at the New York Post, Susannah suddenly developed a strange combination of symptoms. She began having unusual perceptions, such as auditory hallucinations and delusional beliefs. Paranoia was frequent, and she often thought that her friends and family were out to harm her. She became hypersensitive to sounds around her, and developed a fever. Eventually, the disease led to a seizure, which brought her into a hospital.
At this point, she was seen by several doctors, many of whom incorrectly diagnosed her symptoms. At first, the simplest and most predictable diagnosis was alcohol withdrawal. It is well known that chronic alcohol users who stop their alcohol use cold-turkey experience many of these same symptoms. Notably, delirium tremens is common in alcohol withdrawal which can cause hallucinations, erratic behavior, and seizures. Many of those first doctors recommended that Susannah seek medical attention for her alcohol withdrawal, but this was not effective.
The next misdiagnosis was schizophrenia. Schizophrenia can present itself with auditory hallucinations, like the ones Susannah was experiencing. It is also capable of producing disorientation and delusions, such as the persecutory delusions that she was experiencing. Also, schizophrenia most often presents with symptoms while a person is in their twenties or thirties, the age that Cahalan was at the time of her initial diagnosis. Schizophrenia is also relatively common, affecting about 1% of adults in the US. This misdiagnosis led to medication that had no effect on Cahalan's symptoms.
Other doctors simply wrote off her symptoms as psychosis, which produces those same symptoms. Despite all of these attempts to figure out what was going on, none of the proposed treatments were successful at reversing her symptoms.
After being seen by a variety of medical experts and being given several mistaken diagnoses, she eventually met Dr. Souhel Najjar, the man who figured out exactly what was going on with Cahalan's brain.
Dr. Najjar was a neurologist who believed correctly that Cahalan's symptoms were more likely a result of something neurologically wrong with her nervous system rather than a psychological phenomenon. To test his theory, he administered a clock drawing task to assess her nervous system activity. In this simple behavioral test, the patient is asked to draw a circular wall clock and put the numbers on the clock where they belong: the numbers 1 through 12 should appear on a circle around the inner perimeter of the clock face, spaced evenly apart. However, when Cahalan had tried to do this simple task, she ended up putting all the digits along one half of the clock while completely ignoring the other half. Dr. Najjar concluded that there was something wrong with the activity in Cahalan's brain. He pointed to inflammation as being the underlying cause of her symptoms.
With anti-NMDA receptor encephalitis, the body begins producing antibodies against one population of glutamate receptors, the NR1 or NR2 subunits, sometimes also called Gln1 subunit. The body normally uses these subunits to make the NMDA receptor, a transmembrane protein that contributes to glutamatergic communication between neurons. However, when the immune system begins targeting these receptors, the nervous system begins behaving in very unusual ways, producing some of the symptoms that Cahalan had experienced. The molecular mechanisms of the disease are fairly well characterized. The binding of the antibody to the NMDA receptor causes cross-linking and internalization, without affecting the scaffolding structure or number of synapses (Cellular and synaptic mechanisms of anti-NMDA receptor encephalitis.)
Because the disorder is an autoimmune disease, it can be treated with immunosuppressant drugs. These drugs prevent the immune system from destroying their targets. Notably, they have risks since it makes a person more likely to develop some sort of disease that would have normally been destroyed by the healthy immune system.
Anti-NMDA receptor encephalitis is often associated with some kind of tumor, particularly an ovarian teratoma. If the tumor can be safely removed, it can cause a reversal of the symptoms (Successful treatment of anti-NMDA receptor encephalitis with early teratoma removal and plasmapheresis).
Dr. Josep Dalmau, who is credited with discovering anti-NMDA encephalitis, is aware that the disease is often misdiagnosed. The symptoms are frequently mistaken for some complex psychiatric condition rather than a more concrete solution (Anti-NMDA Receptor Encephalitis in Psychiatry). The disease is rarely diagnosed - Cahalan was the 217th person to be diagnosed with the disease since it was first defined in 2007.
In most cases of anti-NMDA receptor encephalitis, the disease follows a prescribed time course of symptoms. Early, for the first week, the symptoms are not particularly noticeable. This phase, called the viral prodrome phase, is almost entirely undiagnosed. The second phase is the psychosis phase, where the psychiatric symptoms (hallucinations, mania, delusions, disorganization) begin to become more apparent. Here, the disease is often misdiagnosed for some of the more common psychiatric conditions that present with similar symptoms, such as schizophrenia or psychosis. Within months, the more severe neurologic complications arise, such as motor disability, coma, or seizures. After this stage, the patient may experience persisting changes in mental status or executive function. (Anti-NMDA receptor encephalitis, autoimmunity, and psychosis)
With successful treatment, if given rapidly enough within disease progression, most patients are able to fully recover.
There is, however, a simple test to figure out if a person has the disease or not. Because the disease is an autoimmune disease, it is possible to test the blood for the presence of the antibodies that target the NMDA receptors.