Josep Dalmau: “I never thought I would discover a new disease”

2024-05-11 10:01:19
Susannah Cahalan’s name is as unknown in Spain as Josep Dalmau’s probably is. Her paths crossed in 2007 when this young journalist thought she had gone crazy. The 24-year-old woman entered an inexplicable state of delirium and paranoia. She heard voices and hallucinated. She couldn’t talk or walk. She was terrified and the baffled doctors did not know how to establish a correct diagnosis. As she tells in her book ‘My Brain on Fire’, Cahalan herself, a doctor at the University of Pennsylvania, would diagnose her, thanks to the suspicion of the neurologist Souhel Najjar who sent the blood samples to this university, with something called encephalitis. autoimmune against the NMDA receptor. The doctor to whom Cahalan’s blood samples were sent was the Spanish Josep Dalmau, ICREA researcher at the August Pi i Sunyer Biomedical Research Institute (IDIBAPS) of the Hospital Clínic of Barcelona, ​​who works between Barcelona and Pennsylvania (USA), and that it has already discovered 12 of the 18 encephalitis of this type. Thanks to his work, and that of his team, it has been possible to accelerate the diagnosis and refine the treatments of diseases that affect 1 in every 250,000-500,000 people. Related News Standard health No The disease brought by ticks settles in hospitals Raquel C. Pico In 15 years, admissions due to Lyme disease have increased by 191% in Spain; Among the causes are high temperatures, which create a favorable environment for these insects. When you were studying, did you ever think that you were going to discover a disease? No, the truth is that I never thought I would discover an illness. How is it done? It’s a mix of work and luck. In my case it was having a great interest in a certain group of neurological problems. I say that you always start with the patient, who is unknown about what he has, and then you go to the next level, which is to investigate, investigate, and investigate. You ask yourself questions like why do these patients have this series of symptoms and what is the cause? From here, experience helps. It’s work, luck and a little experience. The experience allows you to compare with other cases, with other situations and other patients that you have seen previously and who could have the same thing and who were classified with basically unnamed diseases, such as idiopathic encephalitis. It was the study of a group of these patients that led us to the next step, which was to investigate in the laboratory if there was any evidence that what Susannah Cahalan had was related to a process mediated by the immune system; It was about identifying the antibodies, the brain proteins. To fight the disease, the immune system produces antibodies, that is, Y-shaped proteins that attack foreign invaders such as bacteria or viruses. But, sometimes those proteins can attack our own body. And this is known as autoimmune disease. In Cahalan’s case, those antibodies were directed against a receptor in her brain: NMDA, which is involved in the process of how brain cells communicate with each other. This receptor is important because it participates in normal brain function: from memory to breathing. Everything is a path. But the first steps are the essential ones. How do they find the disease and classify it? Many patients have been misdiagnosed with schizophrenia and other mental illnesses. In our specific case, it was not studying patients with psychiatric problems, but rather analyzing patients who had a neurological problem, although in many cases they also had a psychiatric component. But it was very clear in the first patients studied with one of the encephalitis, encephalitis with antibodies against the NMDA receptor to be more precise, that there was no psychiatric component. But we didn’t know the cause. It’s a job, luck and a little experience. What is encephalitis? Encephalitis is a term that encompasses hundreds of diseases, because encephalitis simply means inflammation of the brain. Any infection of the brain is encephalitis caused by an infection. But those that have meant a paradigm shift, a change in the way of thinking, have been a specific group of immune-mediated encephalitis. In this group, patients have antibodies, which are directed against proteins in the brain, and it is the antibodies themselves that cause these alterations in these proteins, which then translate into a very wide variety of symptoms. Depending on the disease, the type of antibody, the group of symptoms is different. And some can cause significant problems when making the initial differential diagnosis since they can be confused with a psychiatric disorder. How do they originate? In some it is a tumor – not necessarily malignant, such as a teratoma – that initiates the autoimmune process and in others, although not in all, it may be the herpes simplex virus – herpetic encephalitis. The tumor, in some way, is involved in the onset of the disease. This tumor expresses brain proteins that the immune system recognizes as foreign proteins, and therefore develops an immune response against the tumor and then against the brain proteins themselves. But it may happen that the tumor does not exist. There are some encephalitis that are initiated by a brain viral process. And then there are 40% of patients in whom the cause of onset is not known. Is there any common pattern in these diseases? In encephalitis mediated by antibodies against the NMDA receptor, the majority of patients are young people – the median age is about 20 years. Approximately 40% are boys or girls of pediatric age, under 18 years of age, with a clear predominance of women, approximately 70%. The most common tumor is also a teratoma. Josep Dalmau isabel permuy A film story In 2007, Josep Dalmau’s team described the first of these autoimmune encephalitis. As he explained during his speech at the IX Tatiana Conference at the Autonomous University of Madrid, they had been researching another group of these diseases always related to cancer for more than 15 years with his group at the University of Pennsylvania. From the New York hospital where she was admitted, Calahan was consulted about this strange case of a young woman who had entered the hospital with a psychiatric condition and had been admitted for weeks due to multiple neurological disorders and deterioration in the level of consciousness. Dalmau says that all tests were negative and he remembers the cases of three patients from the past who were identical and who had cerebrospinal fluid, and he looked for what was repeated in them from an immunological point of view until the pieces of the puzzle fit together. We think of an inflammation in the brain that appears as an immune response and attacks certain proteins in the brain. Years later, Calahan wrote the book in which he told it all and later, the story was made into the film ‘Brain on Fire’. And the treatments? The vast majority are treated in a fairly similar way: eliminating the immune response. However, until there are clinical trials with new drugs or new therapeutic strategies. Those currently used usually work quite well, in over 80% of patients, and are aimed at eliminating antibodies from the cells that produce them. However, they do not always work 100% and generally many patients need a second line of treatments, based on the elimination of the cells that produce them – cells, B lymphocytes – and this is done with monoclonal antibodies. But the truth is that some treatments are still lines of research in progress. And is there a risk that, once cured, it could reappear? Like all autoimmune diseases, there is always a risk of recurrence. But, for example, curiously, in most of these antibody-mediated autoimmune encephalitis the tendency to recur is relatively low. If patients are treated intensively in the acute phase, there is little risk of recurrence. It is, for example, much lower than the recurrences seen, for example, with multiple sclerosis.
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