Around Christmas 2005, Spanish neurologist Domingo Escudero wasn’t at his best. He was running a fever and only wanted to wear blue, would go from having trouble putting a sentence together to the words flowing out in a torrent. He had taken up smoking again and was drinking heavily. Pilar Latorre, a friend and fellow neurologist at the Can Ruti Hospital outside Barcelona, noticed his erratic behaviour; she had heard him talking obscenely about the women he was meeting through a dating website and assumed that the demands of his working environment were having an effect on his stress levels. She offered to take him to see a doctor. Escudero had separated from his wife four years earlier, and he and Latorre had cultivated their friendship as they shared an interest in José Ángel Valente, Philip Roth and the latest discoveries in clinical neurology. So, despite his growing confusion, he accepted.
At the hospital, psychiatrists and neurologists observed his uninhibited, maniacal behaviour and fits of delirium but were unable to locate the source of his agitation, and he was sent home with a handful of sedatives. There on his sofa, Escudero sensed that something in his brain was still not right. He had trouble stringing thoughts together and his memories were fuzzy, yet he was overcome with highly anomalous euphoria. At times he thought he was hallucinating. Worrying that he would soon lose control, he took up paper and pen and wrote up his own differential diagnosis, one beyond the realms of possibility: limbic encephalitis caused by borrelia. He sensed that his ravings had an autoimmune basis but hesitated calling it just limbic encephalitis. Escudero was very familiar with the havoc autoimmune diseases can wreak, but a few weeks earlier he had gone hiking and been in contact with dogs, so he opted for a more conservative diagnosis, attributing his condition to borrelia, a bacterium transmitted by ticks. His confusion had led him to mix autoimmunity with tick-borne illness; an impossible diagnosis that nevertheless pointed to encephalitis.
Escudero had been fascinated by autoimmune diseases since he was a child, in part due to an illness his sister Carmen suffered at the age of fifteen. He was about seventeen when Carmen’s ankles swelled up strangely and she felt a crushing weight on all her joints, which were also starting to balloon. She was having trouble keeping her balance. Medical tests were inconclusive, so her doctor decided her symptoms could either be psychosomatic or the result of rheumatic fever, and ordered bed rest. Carmen spent a long time convalescing, watching enviously as the healthy children around her developed at a quicker rate.
When they diagnosed her, her brother had already begun studying medicine, and he would sit by her bedside telling her about the latest advances in rheumatology. Two years after her first outbreak, Carmen was admitted to the hospital for a backache that had her bent over in pain. The new battery of tests detected the HLA-B27 histocompatibility antigen in her body. A doctor came to her room to inform Carmen that she was suffering from ankylosing spondylitis, an autoimmune disease. This meant that, due to an erroneous diagnosis, Carmen had been taking the wrong medication over two torturous years.
Escudero made autoimmune diseases the subject of his doctoral thesis. He travelled to the US to study them further – at Baylor University Medical Center in Dallas in a clinical observership with neurologist Herbert Irwin Leiman; and in Detroit at the Henry Ford Hospital, attending numerous symposia while there. When he fell ill in 2005, he had extensive knowledge of the symptoms of limbic encephalitis and could self-diagnose, but it was also clear that something was wrong with his brain. Two days later, he was overcome with consecutive psychotic outbursts and had to be forcefully subdued by several nurses as he was admitted to Can Ruti. Amid insults, obscenities and aggressions, Escudero claimed that he was suffering from encephalitis.
While he certainly wasn’t in a state to be taken seriously, his colleagues performed an MRI scan and several other tests in order to rule out this hypothesis; his diagnosis remained unconfirmed. In the end, the doctors attributed his illness to psychiatric causes and had him committed to the acute psychiatric ward at Bellvitge University Hospital in Llobregat, near Barcelona. They put him in a straight jacket and strapped him to a bed while antipsychotic drugs flowed through his veins. Escudero’s condition seemed so unmanageable that the head doctor, Dr. Menchón, had to ask the patient’s nineteen-year-old daughter Clara for signed consent just so her father could undergo electro-convulsive therapy. Clara felt out of her depth. In the end, it turned out that she didn’t have to make that decision: a new examination showed signs of cardiovascular disease. Electric shocks increase both heart rate and blood pressure so much that they can cause highly dangerous arrhythmia, and Escudero’s heart condition led Dr Menchón, who was already hesitant about the effectiveness of ECT, to abandon the idea.
Over the course of the month Escudero spent at Can Ruti, he tried to strangle three of the women closest to him. His sister Carmen claims that when he grabbed her by the neck, ‘his body was like a rock. It wasn’t his. It was like he was possessed. It sounds crazy, but it made me think of the girl in The Exorcist.’ The fact that the doctors and nurses taking care of Escudero were also his colleagues added to the discomfiture of the situation. ‘It was very shocking and very sad,’ says Rebeca, the nurse on duty the day Escudero was admitted. ‘He should be the one curing people. I never imagined a doctor in that place, in that condition.’
Escudero remembers those days only intermittently. In Bellvitge, under the effect of antipsychotics, clonazepam and lormetazepam – two benzodiazepines in the Valium family – his insomnia had him pacing the halls at night. He often crossed paths with a man who had a large scar on his skull and who was always reading from a book of world history. He remembers his anguish on waking up each day, the overcrowded smokers’ room, watching the cars silently moving along the highway from a hermetically sealed window. After spending a month there, he was sent to PAIMM (Programa d’Atenció Integral al Metge Malalt), a hospital for medical personnel only. Designed to protect patients’ anonymity, the hospital focused primarily on the rehabilitation of addicts. So Escudero was now living among kleptomaniac doctors, drug-addicted anesthesiologists, bulimic nurses, etc. He assumes that was the reason the psychiatrist there was so insistent he’d discuss his recent fondness for whisky or how long he’d spend on certain websites, mistaking Escudero’s frequent visits to an online dating website with procuring sexual services. Escudero refused to qualify such behaviours as addictions and grew increasingly convinced that he didn’t belong in such a place. Five doctors finally agreed that he was suffering from a bipolar disorder; they medicated him accordingly. ‘I have examined patients with bipolar and my symptoms were completely different,’ he says. ‘But I took everything they prescribed me.’
A few weeks later, he was sent to live with his parents on the condition that he continue visiting the PAIMM every day, including attending therapy sessions ‘that were driving me nuts. I knew I shouldn’t be there.’
*
Two months before Escudero was hospitalized, neuro-oncologist Josep Dalmau published an article in Brain, a scientific journal, about a new syndrome that was primarily affecting young women and was characterized by psychiatric symptoms, hyperventilation and ovarian teratoma (a kind of tumor). It was a new type of autoimmune encephalitis.
Working at the Memorial Sloan Kettering Cancer Center in New York and the University of Pennsylvania, Dalmau studied how certain types of cancer confuse the immune system by triggering attacks on the brain from the very system that should be protecting it. He was trying to figure out a way to stop these attacks. ‘We treated a young woman whose first symptom was a very serious behavioural change,’ Dalmau says. ‘She was suffering from psychosis, had a sudden drop in her level of consciousness and went into a coma. She had to be placed on a respirator. After months of research, we still had no diagnosis and decided to try immunotherapy, blindly. She made a full recovery.’
In 2005, Dalmau’s team treated seven other patients with similar symptoms and it turned out that, ‘each patient presented different antibodies, which means that each patient opened the door to a different disease for us.’ Dalmau confirmed that all the young women with ovarian teratoma responded equally to the treatment, and in 2007 he published his initial assessment. ‘We started to get emails from all over the world,’ explains Dalmau, while showing me pictures of young Indian and Japanese women convulsing on stretchers. ‘We began to realize the importance of our research. This was a new disease, one that had always existed and that had killed a lot of people because, depending on the country, they would let the patients die or unplug them thinking they were beyond hope.’ Some of the afflicted entered into a catatonic state that led to lethal respiratory failure. In others it triggered untreatable epileptic seizures or fatal fluctuations in their heart rate or blood pressure. In coma for weeks or months, several patients died from infections or nutritional deficiencies related to their illness.
Meanwhile in Barcelona, Escudero moved into his parents’ house in April and tried to recover there. He would soon turn fifty years old and was devastated to find himself dependent on them. He contemplated suicide. The following month, he went back online, although he still couldn’t handle being in front of a screen for very long. That autumn, the doctors recommended he try to return to his own apartment in the Guinardó neighborhood of Barcelona, in an attempt to regain some autonomy. He was slowly becoming more mentally alert. He began driving again. In January 2007, a year after his psychotic break, he went back to work.
Of his first day back at Can Ruti, Escudero remembers only the fear and the feeling that he was under observation and being talked about. His mind grew increasingly clear on the following days, although he can’t tell me much about them either. He resumed contact with his old world, including Elsa, a young neurologist he’d been flirting with before the break. They began dating.
*
In Pennsylvania, Dalmau was working alongside his wife, the American neurologist Myrna Rosenfeld, when they discovered the antibody that was attacking the brain’s NMDA receptor, anti-NMDAr, thus defining the first of a series of autoimmune encephalitides characterised by their effects on neuropil surface receptors. NMDAr is a type of protein found in nerve cells that acts as a receptor for the neurotransmitter glutamate; its role in the transmission of electrical signals between brain cells is key to proper memory function, behaviour and cognition. Dalmau and Rosenfeld proved that the disease attacked the patients’ memory and behaviour, making them psychotic. And they defined it as autoimmune encephalitis.
Prior to 2007, Dalmau had been best known for his work on what are sarcastically referred to as fascinomas, fascinating but very rare diseases. Neurology, with its aura of difficulty and so many rare diseases and syndromes that affect such a tiny minority, is fertile ground for fascinomas. There are no exact figures, but it is believed that they affect only one person among several hundred thousand. A rare illness exhibits between one case per thousand and one case per 200,000. On the face of it, autoimmune encephalitis seemed to be as rare as Eaton-Lambert myasthenic syndrome (a neuromuscular disorder that blocks myoneural transmission) or Whipple’s disease (which hampers the small intestine’s ability to absorb nutrients). So, before announcing the news, Dalmau warned his colleagues, ‘This time I will bring you something other than a fascinoma.’
The following year, Dalmau’s team identified more than a hundred cases of encephalitis. Articles in the Lancet Neurology and in the New York Times catapulted the neuro-oncologist’s discovery into the public eye. Tabloids reported that the illness suffered by the ‘girl in The Exorcist’ had been found. Dalmau had discovered a popular disease in the twenty-first century, a feat akin to finding a new mammal species when it’s commonly believed they’ve all been identified. But his findings still had to be disseminated and accepted. The symptoms for autoimmune encephalitis continued to confound doctors around the world.
In 2009, having completely recovered from his strange episode, Escudero attended a talk by Dalmau in Barcelona. When he heard Dalmau describe the symptoms of autoimmune encephalitis, he thought to himself, ‘That’s what I had.’ However, he was a fifty-something-year-old man and, despite the fact that Dalmau’s team had come across a few similar patients, his age and the lack of a teratoma left room for doubt.
During his talk, Dalmau confessed that he didn’t know the origins of this illness, though he surmised that it was two-thirds unspecified environmental causes and one-third genetic. He said that, in addition to the numerous cases in young women with ovarian teratomas, they had detected cases in adult men, in children of both sexes and in patients with the viral infection herpetic encephalitis. He hadn’t discovered the root of the attack against the NMDA receptor in the rest of those affected, which amounted to 40 per cent of the cases. However, they all showed a genetic predisposition to autoimmune diseases.
Dalmau also noted that in children the disease was usually diagnosed as autism, which in some cultures is considered a form of satanic possession. He added that it was difficult to pinpoint any other illnesses in which the patient would recover completely from a comatose state.
Escudero made a strong recovery and decided to focus his research on this new disease: after a few months, his team diagnosed the first cases of NMDA receptor antibody encephalitis, and in January 2011 he was promoted to head of neurology at Can Ruti.
The pressure of his new position sent his stress levels through the roof. By his third month on the job, Escudero became unusually irritable and started talking quickly and unintelligibly. On the night of the explosion at the Fukushima nuclear plant, he scribbled pages and pages in which he mixed ideas about the accident with ones about his mental state. Elsa, who was by then his wife, insisted the doctors perform a lumbar puncture to determine if her husband was having a second outbreak of the encephalitis that he was so obsessed with. The morning after the procedure, Escudero suffered a heart attack. As he was recovering, he got the results of the lumbar puncture: positive – he was indeed suffering from autoimmune encephalitis. After five weeks of proper medication, the neurologist’s condition improved and he finally got better.
‘It was what I had diagnosed myself with from the beginning,’ Escudero then recalled. ‘This disease has been my lifelong obsession, and I’m very lucky to have come down with it.’
*
This past March, Escudero and Dalmau both attended the Lancet Neurology Autoimmune Disorders Conference in Barcelona. The neurologists exchanged notes on the many cases that they had failed to detect throughout the years. Escudero reflected on his own situation and on how his own colleagues had been the ones to wrongfully diagnose him. ‘For a while I was resentful. I thought they hadn’t done enough, that if I was able to come up with the diagnosis, why couldn’t they . . . but it wasn’t hard for me to get past that. After all, when I got sick no one knew what NMDA receptor antibody encephalitis was.’
At the conference in Barcelona, Dalmau shook many hands. He is considered a leading figure in contemporary neurological science. The American Academy of Neurology awarded him the 2010 George W. Jacoby Award, which recognizes people who have done notable experimental work in the field. In 2011 he joined the ICREA (Catalan Institute for Research and Advanced Studies) as a researcher. In addition to support from the CELLEX Foundation, the University of Barcelona has given him a laboratory to continue his studies, the results of which will continue to be disseminated on a large scale thanks to his international renown.
‘Dr. Dalmau, help us,’ is a recurring sentence in emails received over the last decade, during which he’s patented the diagnosis for detecting this disease. ‘We receive some three thousand cases a year, although they only send us the ones that aren’t showing signs of improvement.’ In this period of time, his team has identified nine other diseases. Dalmau asserts that ‘advances in neuroscience are as important as cancer research. We are talking about mining the depths of memory, about Alzheimer’s, about the mechanisms of awareness.’ That is the reason he calls for more of an investment in this discipline: there is still so much to learn. At this point, more than a dozen autoimmune encephalitides have been identified, each with its own specific mechanisms and clinical manifestations. Some have required unique treatment. Today, the most common and most studied autoimmune encephalitis is the one caused by antibodies attacking the NMDA receptor. It has gone from fascinoma to simply fascinating, particularly for Dalmau’s team, which is on the cutting edge of autoimmune encephalitis research.
Escudero had a third outbreak in September 2014, from which he was able to recover in three weeks. While he weighs the possibility of returning to work directly with patients at the hospital, he makes an effort to lead a calmer life, believing that one of the unspecified environmental causes that trigger the illness is stress. In any case, Escudero realises that his experience is incomparable.
Every once in a while, Escudero puts aside his scientific instinct, looks at his passions, his obsession with autoimmunity, the daily tensions he put up with for years and he wonders, ‘To what extent did I provoke my illness?’ As Escudero’s colleague Alfons Moral put it, ‘A neurologist falling ill with an illness he’s obsessed with and almost self-diagnosing before the disease itself is discovered . . . It’s a unique story. The chances are one in two . . . no, one in three billion.’
A version of this essay was first published in Spanish in La Vanguardia
Photograph courtesy of Proxy Design
