Headache & Pain
Mar. 11, 2023
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In this installment of our Featured Contributor series, we are pleased to feature Francesc Graus MD PhD, who serves as Sr. Associate Editor for the Neuroimmunology subspecialty and on the Executive Committee for MedLink Neurology. Dr. Graus was Head of the Neurology Service at Hospital Clínic de Barcelona until 2018 and is currently Emeritus Investigator of the Pathogenesis of Autoimmune Neuronal Disorders Program at IDIBAPS (Institut de Recerca Biomedica Agust Pi I Suñer). He was founder and president of the European Association of Neuro-Oncology (EANO) and received the title of Doctor Honoris Causa for Lyon University.
Dr. Graus’ area of research is paraneoplastic neurological syndromes and autoimmune encephalitides and he led the panel of experts that first defined strict criteria for their diagnosis. His research has been important for the confirmation of the immune hypothesis that the underlying tumor triggers an autoimmune attack to the nervous system causing the neurological dysfunction. The antibodies he identified are now widely used for the diagnosis of these syndromes. His current research is focused on the clinical manifestations and immunological features of anti-IgLON5 disease, a disorder that was initially characterized in 2014 and represents a bridge between autoimmunity and neurodegeneration.
Tell us about your early background.
I was born in 1953 in a Barcelona that was just starting to recover from the devastating effects of the Spanish civil war and the post-war punishment for supporting the Republic. I was raised in a middle-class family with no previous relatives with university careers. My father was a graphic designer, and my mother was a secretary until my younger brother was born. I went to a catholic school. My mother insisted that I had to receive a laical education at the French Institute, which was near where we lived. However, my father, despite being an agnostic, did not approve my mother’s idea. He had very bad memories of the concentration camp where the French had put him when he, as part of the republican army, had to cross the border at the end of the war. The catholic school was not bad, but when I talked with friends from the neighborhood and they explained what they were doing at the French Institute, I concluded that my mother was right and that past experiences, no matter how bad they had been, never must dictate future decisions.
What or who motivated you to pursue a clinical or scientific career? How did you get interested in neurology and your subspecialty?
I studied medicine at the Autonomous University of Barcelona. During my pre-clinical training, I soon became fascinated by the brain and how it works. My greatest question was whether to go into basic research or to become a clinician. The decision was taken when I started my clinical training and realized I was comfortable seeing patients and very interested in trying to disentangle the neurological disorders. My interest in neurology was not hampered by the fact that I never had the opportunity to listen to the neurology classes as the University went into a strike in protest for the political situation during the semester when the neurology classes were scheduled.
I did my residency at the Bellvitge University Hospital near Barcelona. The residency consolidated my interest in neurology, and in those years, I made two decisions that probably defined my professional career. First, I decided that I had to go to the U.S. I did not expect to go there to make a breakthrough but to see how a department is organized to extract from the clinical care the knowledge to understand, step by step, the neurological disorders. The second decision was to become a subspecialist in neuro-oncology. The decision was greatly influenced by an editorial in the American Journal of Medicine wherein Dr. Jerome Posner explained the important role of neurologists in the care of cancer patients (Posner 1978). Immediately after reading the paper, I had a plan: I would go to the U.S. to be a neuro-oncologist.
Did you have any mentors who guided or inspired you?
Several people have influenced my career, but two stand out for different reasons. The first is Prof. Josep LLuis Martí-Vilalta, a neurologist from de Hospital of Sant Pau of Barcelona who directed my first research project when I was a medical student. He helped me to consolidate my interest in clinical research. I was very proud when the study was published (Marti-Vilalta and Graus 1984). Many doctors think that spending time guiding the projects of medical students is a waste of time. They are wrong, as I found in my case, because their influence may be fundamental to sparking the research interest in young doctors. The second person who most influenced my career is Dr. Jerome Posner, who was the director of the Department of Neurology at Memorial Sloan-Kettering Cancer Center in New York where I trained as a neuro-oncologist. The time I spent with him during clinical rounds, the tips I learned while listening to his case presentations, and, above all, his full support in starting the project of detection of neuronal antibodies in paraneoplastic neurological syndromes shaped my personality. Because of my time with him, I made a full transition from a young, insecure “rookie” to a mature neuro-oncologist.
What do you consider your most significant career achievement to date?
To initiate and consolidate the research of neuronal antibodies first in paraneoplastic and later in other autoimmune neurological syndromes was a significant achievement. Despite earlier observations, the detection of Purkinje cell antibodies in paraneoplastic cerebellar degeneration by Dr. John Greenlee in 1983 and Hu antibodies in paraneoplastic sensory neuronopathy in 1985 when I was working with Dr. Posner represented the first steps in a long road that has culminated in the development of the new subspecialty of autoimmune neurology. Following this research line, we identified in 2014 a previously unknown disorder that we called anti-IgLON5 disease characterized by a combination of sleep disorder, bulbar manifestations, and abnormal movements, and the presence of antibodies against IgLON5, a cell adhesion neuronal protein. An interesting aspect of this disease is that the autoimmune aggression may lastly induce neurodegenerative changes (neuronal hyperphosphorylated tau deposits) in the brain.
Posner JB. The role of the neurologist in the management of cancer. Am J Med 1978;65(1):4-6. PMID 686000
Marti-Vilalta JL, Graus F. The palmomental reflex. Clinical study of 300 cases. Eur Neurol 1984;23(1):12-6. PMID 6714273