A Neuroscientist Reads… Brain on Fire by Susannah Cahalan
Brain on Fire, published by New York Post reporter Susannah Cahalan in 2012, is a powerful autobiographical account of the author’s ‘lost month of madness’.
It all started with a couple of bedbug bites. Well, maybe it did, or maybe they were just in her head. Maybe those tiny marks on Susannah’s arm were simply the first symptom of Susannah’s life-changing illness. It was a period of her life where she came close to death that, perhaps mercifully, she remembers little of. Brain on Fire is Susannah’s opportunity to look back on her illness and reclaim the time she lost. With help from family, friends and her medical notes, she tells the story of her illness to better understand her own condition and to recapture her old identity.
‘It flipped my universe upside down and very nearly sent me to an asylum for life.’
Back in the hot summer of 2009, Susannah Cahalan was a reporter at the New York Post. She was living in a small apartment in downtown New York and had recently started dating her now-husband, Stephen. She was hard-working, successful and full of life; no different to any other healthy 24-year-old.
Yet, within just a few short weeks, everything changed. At first, it was paranoia, fears about bedbugs, underperforming at work and that Stephen was cheating on her. Then came the piercing migraines, and eventually a terrifying seizure that sent her into hospital. Initially, the doctors brushed off her symptom as burnout; she was working too hard and not resting enough. One even suggested that she could be suffering from alcohol withdrawal syndrome, despite Susannah’s repeated protests that she didn’t drink enough for this to be true.
But after returning home, things did not get any better. Susannah’s family started noticing little changes to her personality, like being more argumentative than usual, or her eyes glazing over and staring into space. The seizures also got more frequent, now comprising of whole minutes where she would be unresponsive, or she would be unable to control her limbs, often keeping her arms outstretched in front of her like “zombie arms”.
For a while, Susannah thought she might have bipolar disorder, as her mood swung from hysterical happiness to unexpected bouts of tears. But despite repeated visits to the psychiatrist and numerous EEGs (to measure her brain’s electrical activity to diagnose epilepsy), no one could work out what was happening to Susannah. Finally, just 10 days after her first seizure, she was admitted to hospital.
And so began Susannah’s ‘lost month of madness’.
‘Unlike before, there are now no glimmers of the reliable “I”, the Susannah I had been for the previous twenty-four years.’
In the early days of Susannah’s hospitalisation, various theories about her mysterious illness were thrown about, ranging from cancer (she’d previously had a melanoma removed) to schizoaffective disorder. But as her psychological symptoms waned, other symptoms took their place. She began slurring her words and her short-term memory rapidly deteriorated, terrifying those around her.
In the book, Susannah likens herself to patient HM, a famous neurological case. In 1953, HM underwent surgery to reduce the severity of his epilepsy, which involved removing a piece of his cortex. However, the surgeons also inadvertently removed HM’s hippocampus, the region of the brain associated with our ability to make and recall memories. This left him with severe retrograde amnesia, meaning he was no longer able to form new memories. Just like HM, within just a few days of her admission, Susannah could barely remember what had just happened to her, whether that be what she watched on the TV or discussed with her parents.
It took a very special doctor, Dr Souhel Najjar, a now-famous Syrian-American neurologist, to work out what was wrong with Susannah.
Despite all the high-tech CT scans, MRI scans and EEG recordings of her brain, in the end, it was a simple drawing that helped Dr Najjar diagnose Susannah’s illness. He asked her to draw a clock, just a single circle with the numbers around the edge. Even to a child, this would be a simple task. Yet what Susannah produced was surprising. She was able to draw the circle, but she squashed all 12 numbers onto the right-hand side of the circle.
This revealed Susannah was suffering from left-side neglect. Because the right hemisphere of the brain controls the left side of the body, and vice versa for the left hemisphere, left-side neglect is a phenomenon that can occur when there is damage to the right side of the brain, for example after a stroke. The right side of the brain is unable to process what is going on in the left side of the world, and so when Susannah drew the clock, she couldn’t comprehend that some of the numbers should have been on the left. She knew the total number, just not where they should go. From this, Dr Najjar concluded that Susannah must have something very wrong with the right side of the brain and ordered an emergency biopsy to identify the cause.
A brain biopsy, where surgeons remove a small piece of brain tissue for tests, revealed Susannah had extensive inflammation on the right side of her brain. Her immune system was lighting up her brain, potentially causing long-term damage. The doctors had to identify what was causing this massive immune response, and fast.
Dr Najjar sent this sample to Dr Josep Dalmau, a renowned neuroimmunologist, who finally worked out the cause of Susannah’s illness. Through testing her cerebrospinal fluid, the solution that bathes the brain and keeps it topped up with vital glucose and nutrients, Dr Dalmau was able to diagnose Susannah with anti-NMDA receptor encephalitis, an extremely rare autoimmune disorder.
Anti-NMDA receptor encephalitis
The NMDA receptor is responsible for detecting glutamate, the most abundant neurotransmitter in the brain. NMDA receptors are critical for learning, memory and behaviour, as their activation strengthens the association between neurons. Simply put, “neurons that fire together, wire together”, known to neuroscientists as Hebbian learning, a process that is largely mediated by NMDA receptors. Although NMDA receptors are expressed throughout the brain, they are particularly concentrated in the hippocampus.
Anti-NMDA receptor encephalitis was first identified by Dr Dalmau while working at the University of Pennsylvania. In 2005, Dalmau published cases studies on four women with very similar psychiatric symptoms to Susannah, and through testing the cerebrospinal fluid of these women, he realised that they were all producing immune proteins against their own NMDA receptors. This is known as an autoimmune disease, a condition where the body fails to recognise its own cells and produces antibodies to destroy them, just as it would an invading foreign molecule such as a virus. In lots of cases, although notably not Susannah’s, anti-NMDA receptor encephalitis starts because of a teratoma, a vicious cancer commonly occurring in the ovaries.
And it doesn’t take much depletion of the NMDA receptors to produce severe psychiatric symptoms. Dalmau’s studies on mice found that just a 40% decrease in the number of NMDA receptors in the brain produces psychosis, a 50% decrease leads to memory problems and issues with social interactions, and a 70% decrease produces a catatonic state. This receptor is so critical, in fact, that mice born with little-to-no NMDA receptor expression barely survive past birth, and if they do, they die soon after as they fail to learn to suckle.
The parallels here with the symptoms Susannah was displaying are clear. Anti-NMDA receptor encephalitis is characterised by seizures, paranoia, hallucinations, changes in personality and movement issues, just like Susannah’s “zombie arms”. It also produces massive brain inflammation and swelling, which themselves contribute to the symptoms.
When Susannah was ill, it was estimated that only 10% of patients with anti-NMDA receptor encephalitis were diagnosed. Thanks to Susannah’s story, and the continuing work of Dr Dalmau and colleagues, anti-NMDA receptor encephalitis is now much more widely acknowledged as a potential cause of brain inflammation and is now being tested for in many more patients. However, little is still known about why the condition starts, particularly in patients without cancerous growths, and if there is any way to prevent the potentially fatal condition.
‘When you think all is lost, the things you need the most return unexpectedly.’
With the cause of her illness now identified, Susannah could begin intensive treatment to get her immune system back under control. A potent cocktail of steroids and intravenous immunoglobulin to fight her damaging antibodies helped to reduce the swelling in her brain. Although it was many months before Susannah truly felt like herself again, eventually the treatment was able to reverse all of her symptoms.
Dr Dalmau has also published reports on the stereotypical reversal of symptoms, with a patient gradually regaining awareness and the ability to make memories. 70% of patients are able to make a full recovery, with only 5% experiencing permanent disability. However, for those that do recover, their journeys often involve passing back through the early stages of the disease. In Susannah’s case, this meant the re-emergence of her disabling paranoia, a scary symptom for patients terrified they might be relapsing.
What triggered Susannah’s illness is still unknown. Maybe there really were bed bugs, and the bites started off a cascade of immune responses that ended in her illness. Or maybe it was something else, and Susannah is unlikely to ever find out the true cause.
A neuroscientist’s view
As a neuroscientist, Susannah’s story was a fascinating insight into the patient experiences behind the illnesses you read about in textbooks. It’s an incredible example of how state-of-the-art research combined with exciting experimental medicine can work together to save lives. In particular, I found the diagnosis of Susannah’s disease intriguing, how Dr Dalmau used a sample of cerebrospinal fluid on rat brain slices to work out which dangerous antibodies she was producing.
Moreover, this is far more than just an account of the author’s own experience. Susannah eloquently articulates what was going on in her brain during her illness. She references some of the most famous cases in neuroscience and draws interesting parallels to her own case, making these complex ideas understandable to even those with no scientific background.
Brain on Fire is an engaging combination of a heartbreaking yet hopeful story and an intriguing case study on the devastating nature of neurological diseases. It is undoubtedly a moving read for those experiencing chronic illness, raising awareness for a rare yet increasingly diagnosed disease. On top of that, Susannah’s account is also a glowing example of how powerful and captivating good writing can be, inspiring scientists and journalists alike.
