“I never thought that I would discover a new disease”
Name Suzanne Cahalan In Spain he is as unknown as, probably, Josep Dalmau. Their paths converged in 2007, when a young journalist thought she had lost her mind. The 24-year-old girl entered an inexplicable state. … delirium and paranoia. I heard voices and hallucinated. He could neither speak nor walk. She was terrified, and the doctors were at a loss and did not know how to make the correct diagnosis.
As he says in his book:My brain is on fireIt was Cahalan herself, a doctor at the University of Pennsylvania, who diagnosed her, thanks to the suspicion of neurologist Suhel Najjar, who sent blood samples to the university, of so-called autoimmune encephalitis against the NMDA receptor.
The doctor to whom Cahalan’s blood samples were sent was the Spaniard Josep Dalmau, an ICREA researcher at the Institute of Biomedical Research August Pi and Sunier (IDIBAPS) of the Barcelona Hospital Clinic, which operates between Barcelona and Pennsylvania (USA), and that 12 of the 18 encephalitis of this have already been detected type. His work and that of his team have led to faster diagnoses and improved treatments for diseases that affect one in every 250,000 to 500,000 people.
When you were studying, did you ever think that you would discover a disease?
No, the truth is that I never thought I would discover the disease.
How it’s done?
It’s a mixture of work and luck. In my case, it was a strong interest in a specific group of neurological problems. What I’m saying is that you always start with the patient who doesn’t know what he or she has, and then take it to the next level: explore, explore, explore. You ask yourself questions such as why do these patients have this series of symptoms and what is the reason? Experience helps here. It’s work, luck and a little experience. Experience allows you to compare with other cases, with other situations and other patients whom you have seen before and who could have the same thing and who were classified as fundamentally unnamed diseases, such as idiopathic encephalitis.
It was the study of a group of these patients that led us to the next step: finding out in the laboratory whether there was any evidence that what they had Suzanne Cahalan This was due to a process mediated by the immune system; We were talking about identifying antibodies and brain proteins. To fight disease, the immune system produces antibodies, or Y-shaped proteins, that attack foreign invaders such as bacteria or viruses. But sometimes these proteins can attack our own body. And this is known as an autoimmune disease.
In Cahalan’s case, these antibodies were directed against a receptor in his brain: NMDA, which is involved in how brain cells communicate with each other. This receptor is important because it is involved in normal brain function, from memory to breathing.
Everything is a path. But the first steps are the most important.
How do they find the disease and classify it?
Many patients were misdiagnosed with schizophrenia and other mental illnesses. In our particular case, we were not talking about patients with psychiatric problems, but about analyzing patients who had neurological problems, although in many cases they also had a psychiatric component. But in the first patients examined with one of the encephalitises, or rather, encephalitis with antibodies against the NMDA receptor, it was very clear that there was no psychiatric component. But we didn’t know the reason.
It’s work, luck and a little experience
What is encephalitis?
Encephalitis is a term that covers hundreds of diseases, as encephalitis simply means inflammation of the brain. Any brain damage is encephalitis caused by infection. But those that represented a paradigm shift, a change in way of thinking, were a special group of immune-mediated encephalitis. In this group of patients, patients have antibodies directed against proteins in the brain, and it is the antibodies that cause changes in these proteins, which then lead to a very wide range of symptoms. Depending on the disease, the type of antibodies, the groups of symptoms are different. And some can cause serious problems in the initial differential diagnosis because they can be confused with a mental disorder.
How do they arise?
In some, the autoimmune process is initiated by a tumor – not necessarily malignant, such as a teratoma, and in others, although not all, it may be the herpes simplex virus – herpetic encephalitis. The tumor is involved to one degree or another in the occurrence 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 viral process in the brain. And another 40% of patients whose cause is unknown.
Is there any general pattern in these diseases?
With encephalitis mediated by antibodies to the NMDA receptor, the majority of patients are young people – the average age is about 20 years. Approximately 40% are boys or girls of pediatric age under 18, with a clear predominance of women, approximately 70%. The most common tumor is also teratoma.
What about treatment?
The vast majority are treated in a fairly similar way: eliminating the immune response. However, no new drugs or new therapeutic strategies have yet been tested in clinical trials. The ones currently used usually work quite well, in more than 80% of patients, and are aimed at eliminating antibodies from the cells that produce them.
However, they do not always work 100%, and typically many patients require a second line of treatment based on eliminating the cells that produce them – the B cells – and this is done with monoclonal antibodies. But the truth is that some treatments are still under research.
And is there a risk that after healing it may appear again?
As with all autoimmune diseases, there is always a risk of relapse. But, for example, interestingly, in most cases of antibody-mediated autoimmune encephalitis, the tendency to relapse is relatively low. If patients are treated intensively in the acute phase, the risk of relapse is negligible. This is, for example, significantly lower than the relapses observed, for example, in multiple sclerosis.