A Neuroinflammation Story
Who knows how it started? Did those two mysterious red dots on a vein on her arm mean anything? Could that businessman who sneezed on her in the subway triggered her illness? Or did her biological stars just suddenly align in the strangest configuration ever?
Nobody ever figured out what triggered Susannah’s “month of madness” and in the end it didn’t matter. What mattered was that a young New York Post reporter quickly got very ill and for quite a while nobody knew what to do about it.
This is not a story about chronic fatigue syndrome or fibromyalgia but it could be. The subplots running through it – a woman with the mysterious illness, the predisposition to look for a psychological cause, the negative test results, the misdiagnoses, the strange “brain” symptoms – could be patched onto many ME/CFS and FM stories, and indeed other mysterious illness stories.
Susannah’s story shows how bad neuroinflammation – a possible cause of chronic fatigue syndrome and/or fibromyalgia – can get, how much remains to be learned about the brain and at the same time how quickly the medical researchers are moving forward. Ultimately her story provides hope for people with mysterious central nervous systeme disorders.
Susannah chronicled her story in a best-selling book called “Brain on Fire: My Month of Madness“.
Her Brain on Fire
Susannah Callahan was a young talkative, funny and dedicated New York Post reporter when her month of madness began. First came a unreasonable fear of bedbugs, then a flu-like episode, then a search through her boyfriend’s emails and letters. Even as she was appalled at the boundaries she was breaking she keep breaking them. She didn’t feel like herself; she was anxious, nauseous and unsettled.
When her left hand went numb her gynecologist fixed her up with a neurologist described as “one of the best in the country”. Except for some swollen lymph nodes. though, all her tests were normal. Maybe, he said she had mono. Basically he told her she was OK and to relax.
But she wasn’t. Over the next week she had trouble sleeping, was overwhelmed by the colors and bright lights in the city, and her erratic behavior increased. Her moods whipped from one extreme to the other. She thought she was having a nervous breakdown. When she had a seizure in the middle of the night her boyfriend called 911.
Back to the neurologist she went. He proposed she was working and partying too hard and not sleeping. All she needed was rest and to get off the booze. A psychiatrist diagnosed her with a form of bi-polar disorder and put her on medication.
Meanwhile her descent continued. Wild paranoid thoughts filled her mind. She accused her parents of kidnapping her. She tried to dart out of a moving car. Despite the seizure medication she had another one.
Back again to the prominent neurologist she went – this time with her mother – who demanded more tests and better answers. After a normal EEG, however, the neurologist again diagnosed her with alcohol withdrawal. Despite her mother’s protests that her daughter had not had a drink in a week, the neurologist told Susannah to stop drinking and take her medication. (In his notes he reported she was drinking two bottles of wine a night).
Her mother would have none of it and Susannah was booked into 24 hour epilepsy EEG monitoring unit at the New York Langorne Medical Center. As she entered the hospital she had a massive seizure.
Her delusions mounted. She asserted her parents were turning into other people. She felt people on TV were talking about her. She tried to escape. She declared she had multiple personalities. She became so unmanageable she was in danger of being admitted to a psychiatric hospital. Hints were made that that was a place she wanted to be.
Five doctors were quickly on her case. Four days later four more including an infectious disease specialist joined on. As her psychoses began to recede leaving her in a zombie-like state at times a lumbar puncture was scheduled.
The slightly elevated levels of white blood cells found – the first abnormal test results yet – raised hopes she had an infection but further testing at the CDC and New York State Labs found no signs of infection (herpes, Lyme disease, tuberculosis or others) or autoimmunity. Her MRI and CT scans continued to be normal. When a top doctor abruptly quit her case her parents became distraught.
With few positive test results and her options running out, Susannah was in danger of being diagnosed with a mental disorder and ending up, perhaps for the rest of her life, in a psychiatric hospital.
Then one more doctor, Dr. Souhel Najjar joined the team. Najar’s ability to solve some mystery cases at the hospital had made him the go-to man for difficult cases. He discarded the psychosis diagnosis and despite the negative autoimmune test results he put her on five rounds of IVIG.
Susannah, however, continued to worsen. She was diagnosed with catatonia and began making strange Frankenstein-like movements with her arms. Najar ordered another lumbar puncture. This time there was good news; a quadrupling of her white blood cell counts indicated central nervous system inflammation was present – lots of it. Her diagnosis was immediately switched from psychosis to encephalitis.
Najjar’s first examination of her proved to be groundbreaking. When asked to draw the numbers on a clock she fit all twelve hours into the right side of the clock leaving the left side blank. That clue suggested that the right hemisphere of her brain have been ravaged by inflammation – probably by an autoimmune process. Her brain, he said, was on fire.
The probable next step was steroids, plasmaphoresis and/or more IVIG. First, though, Najjar wanted a brain biopsy. Reluctantly her family agreed. The biopsy showed massive numbers of microglial cells attacking her nerves.
The biopsy indicated Susannah had an as yet undiagnosed autoimmune disorder. (She had been tested for only a few out of the hundred or more autoimmune disorders before).
The treatment regimen was brutally simple: massive doses of steroids infused into her over three days to stop the immune attack in its tracks followed by lower doses to quell the remaining inflammation over time.
Meanwhile her blood was sent to a Dr. Joseph Dalmu at the University of Pennsylvania. The results came back positive.
A New Disease
Four years earlier Dalmau had described four young women with psychiatric symptoms and encephalitis. Testing revealed NMDA-receptor antibodies were attacking the hippocampus – the center of memory and learning – and the frontal lobes – the center of higher functioning and personality.
Two years later Dalmau published an account of twelve women with what he now called anti-NMDA receptor autoimmune encephalitis. A year later a hundred women had been identified. By the time Susannah because ill over 200 had been. When her results came back, Susannah Cahalan was the 217 woman to become diagnosed with the illness.
In retrospect, the course of the disease had been very clear. The initial flu-like symptoms reflected the immune system starting it’s ramp up. The psychiatric symptoms occurred as the antibodies attacked the nerves in her hippocampus and frontal lobes. The catatonia was the result of progressive damage.
The brain is radically resilient. Susannah Cahalan
The steroids probably saved Susannah from entering a life-threatening stage of catatonia but her brain damage was severe. She was extremely cognitively challenged and had trouble speaking and smiling. Whether she would ever return to her former self was unclear.
Najjar decided Susannah was too ill to try anything but the nuclear option. He would hit her overactive immune system as hard as he could and in as many ways as he could. Susannah would again get massive doses of steroids, but this time they would be followed by plasmaphoresis to purge her body of the antibodies, and then IVIG to further neutralize the antibodies. She would do this several times. Over the next six months or so she would get 12 IVIG infusions.
Besides this she would be on five drugs: Atvian to prevent catatonia, Geodon for psychosis, Trileptal for seizures, Labetolol for high blood pressure and Colace for constipation and get speech and cognitive retraining.
She began a slow recovery. A month later she wrote that her first real glimpses of recovery had occurred. Five months later she made her first tentative return to work in the New York Post newsroom. A couple of weeks later she dropped her anti-anxiety and anti-psychotic drugs. A year later she felt she’d returned to full health.
..I realized now that my survival, my recovery – my ability to write this book – is the shocking part. ” Susannah Cahalan
Susannah was one of the lucky ones. Without the seizures (not everyone has them) she would have ended up in the psych ward instead of the epilepsy ward. Perhaps she would have found another Najar there – a doctor on top of his game who was aware of a rare disease that had been recently discovered – but there’s no telling. However it happened she was lucky Najar.
(Another case mentioned in the book describes a more typical story. A sophomore in college became paranoid, checked herself into a psych ward, was diagnosed with “psychosis, not otherwise specified”, sedated and released. A month or so later she was admitted to another psychiatric institution. The doctor there rejected the anti-NMDA receptor hypothesis because she wasn’t having seizures. She returned home and eventually became unable to add or do basic physical tasks. She returned to the hospital where her doctors, for the first time, informed her parents that her MRI test a year before indicated she had inflammation.
As they prepared the IVIG a blood clot in her brain caused a massive seizure. During her seizure her father pushed Susannah’s article describing her illness into the neurologists hands. Her test for anti-NMDA receptor encephalitis was positive and she was air-evacuated to the University of Pennsylvania where Dr. Dalmau successfully treated her. She returned to complete health. (Despite proper treatment about 20% of patients are permanently disabled or die.
Thanks to the work of Dalmau, Najjar, Susannah and her book those kinds of stories are disappearing. Since Susannah has diagnosed in 2009 over 2,000 women have been diagnosed with the disease.
The New York Langone hospital also responded well. It put ten doctors on her case and her treatment costs were over $1,000, 000. There’s something comforting about the extent to which the medical system can go at times.
Susannah’s story also revealed the limits of medical technology and how difficult making a diagnosis is the face of limited test findings. Susannah’s MRI’s and CAT scans were never abnormal. Even after she’d had seizures, psychotic episodes, sensory distortions and trouble writing and responding to people the wide blood cell counts in her lumbar puncture – indicating inflammation – were not particularly high.
Her possible diagnoses at that point included hyperthyroidism, lymphoma, Devic’s disease and paraneoplastic syndrome. Only after she started drifting into catatonia were the markedly increased white blood cell counts indicative of severe inflammation present – and only after her antibody tests came back was her diagnosis ensured.
Movement in the Medical Community
Anti-NMDA-Receptor-Encephalitis has surely been around for many years. A search through the medical literature revealed some case reports dating back to the 1980’s but that was it until 2005. Once the disease had a name and a test progress was pretty rapid, however.
At the time of Susannah’s diagnosis in 2009 Najjar believed that 90% of the cases went undiagnosed. Subsequent research suggests that was probably an underestimate. Dalmau’s found other receptor seeking autoimmune diseases since then. He believes by the time it’s all said and done more than twenty autoimmune diseases may be causing cases of”unidentified psychosis”, “encephalitis of unknown origin” and other idiopathic diagnoses.
The understanding of the role anti-NMDA antibodies has broadened as well. They are now believed to play a role in at least some cases of autism, schizophrenia and dementia. Enough evidence has accumulated for a subspeciality called autoimmunity neurology to appear. It’s clearly a growth field.
Susannah’s story is ultimately a hopeful one. The medical research community is responding. How many people with a now mostly treatable disease entered and remain in psychiatric wards is unknown, but since 2009 thousands of women have now been identified with the disorder. Susannah and others have created the Autoimmune Encephalitis Alliance to help spread the word.
It’s not at all clear how, if at all, any of this applies to ME/CFS or FM. Autoimmune encephalopathies, after all, are still believed to be quite rare, but anything that helps explain central nervous system disorders that have defied comprehension is of obvious interest. That the medical community can move so quickly when it feels it’s onto something is encouraging as well.
- Next Up – Health Rising takes a deeper look at new world of autoimmune central nervous system disorders and Dr. Dalmau’s continuing work.