Antonio Culebras MD FAAN FAHA FAASM, Sr. Associate Editor for Sleep Disorders

In this month’s installment of our Featured Contributor series, we’re delighted to feature Dr. Antonio Culebras, Sr. Associate Editor for Sleep Disorders. As a founding Editorial Board member, Dr. Culebras has served on MedLink Neurology’s Editorial Board for 30 years and as a member of MedLink’s Executive Committee for 7 years. Dr. Culebras is Professor of Neurology at SUNY Upstate Medical University and Director of Medical Neurology at Upstate University Sleep Center in Syracuse, New York.

SUNY Upstate Medical University professional bio

Early days

When I was born in Madrid, Spain, 1 year to the day after the end of the Spanish Civil War, my father, a physician, was imprisoned in a concentration camp. His crime, according to Franco’s regime, had been the development of a very successful blood transfusion program to be delivered on the front lines of battle; the program had saved the lives of many Republican soldiers. Surviving soldiers were recycled to serve again, which was, in their view, a crime. The blood transfusion program under the direction of my father, with headquarters at Príncipe de Vergara 36, Madrid, had been developed in collaboration with Dr. Norman Bethune, a Canadian physician who had acquired experience in blood transfusions during World War I. Dr. Bethune, a member of the Canadian Communist Party, moved to China in 1938, where he joined the Mao Tse-Tung forces and once again was pivotal in developing a front-line transfusion program. Mao Tse-Tung was so grateful that he ordered a statue be erected to honor Dr. Bethune and that his name be given to a national university. Today, Norman Bethune Health Science Center of Jilin University in Changchun is a prominent medical learning center in China. In Spain, my father was eventually released and, despite numerous political setbacks, was able to develop a prestigious medical practice in Madrid.

Early learning years

In 1955, I was awarded an American Field Service grant to study for 1 year in an American high school. I was sent to Renton High School in the state of Washington, where I spent a wonderful year absorbing American culture as a junior student. In 1956, following my return to Spain, I entered the faculty of medicine at Madrid University (today Universidad Complutense) and graduated in 1963. I was fortunate to join a selected group of medical students at the Clínica de la Concepción, Fundación Jiménez Díaz, of Madrid, where after graduation, I spent 2 years rotating in internal medicine and a third year in neurology. Throughout this time, I longed to return to the United States.

Training in neurology

My mentor, professor Jiménez Díaz, gave me a letter of recommendation addressed to Irving Page, a world-renowned researcher in hypertension and discoverer of serotonin, based at the Cleveland Clinic. After completing a 1-year mandatory rotating internship at the New Britain General Hospital in Connecticut, where I met my future wife, Susan Zara, I entered the Cleveland Clinic as a fellow in neurology (residents were called fellows).

At the Cleveland Clinic, I met fascinating people. One of my attendings, Dr. Nelson Richards, eventually became president of the American Academy of Neurology (AAN). Dr. Donald Effler, chief of cardiothoracic surgery, and his brilliant collaborator, Dr. René Favaloro, developed the intramyocardial implantation of the internal mammary artery in patients with myocardial ischemia. In 1968, Dr. Effler and his colleagues performed the first cardiac transplant in the Midwest. His fame was worldwide. One of his surgical patients was Crown Prince Khalid of Saudi Arabia, who later became king of that country. At night, I took neurology calls at the cardiac ICU where Dr. Effler’s patients were cared for following surgery. Mandatory retirement at the age of 65 years caught Dr. Effler in the prime of his career. He moved to Syracuse, NY, where he developed a world-class cardiothoracic service at St. Joseph’s Hospital. His colleague, Dr. Favaloro, developed the first coronary bypass procedure using the saphenous vein and, like Dr. Effler, became world-famous. Dr. Favaloro and I often connected at social events, mainly because we were the few Spanish-speaking individuals at the Cleveland Clinic. In 1971, Dr. Favaloro returned to his native Argentina, founding a cardiothoracic institute in Buenos Aires, eventually named Fundación Favaloro, a cardiac and medical bastion in that part of the world. Early government funding was eventually curtailed, and the institute went bankrupt. This disappointment, compounded by a diagnosis of lung cancer, led Dr. Favaloro to commit suicide by shooting himself in the heart in July of 2000.

Training in neuropathology

During my training years in clinical neurology, I became convinced that knowledge of neuropathology was the basis for the localization of lesions in neurology and the road to developing the best diagnostic skills. During my training years at the Cleveland Clinic, access to CT or MR scanning of the brain had not yet arrived; only pneumoencephalography, conventional angiography, cisternography, and basic radiological imaging of the skull were available. Lesions had to be localized using clinical skills and detailed knowledge of brain anatomy. I spoke with the head of the Cleveland Clinic neurology service, Dr. Guy Williams, and expressed my desire to continue training in neuropathology. Boston, the U.S. capital of neurology and neuropathology, was my goal. Dr. Williams advised, “Go and talk to Betty Banker, director of the Division of Neuropathology at the Cleveland Metropolitan General Hospital. She came from Boston and has many connections there. By the way, her husband is Maurice Victor, director of the Neurology Service, also at Metropolitan.” Eventually, Maurice Victor became co-author with Raymond Adams of the textbook Adams and Victor's Principles of Neurology (Adams and Victor 1977).

Following ‘Red’ Williams’ advice, I went to see Betty Banker. She was very friendly. “By the way,” she said, “the head of neuropathology at the Boston Veterans Hospital in Jamaica Plains, affiliated with Boston University, is Dr. José Segarra, also a Spaniard. I will send him a letter on your behalf.” Pursuing that lead, I traveled to Boston and interviewed with José Segarra and Robert Feldman, chairman of the Department of Neurology at Boston University. Shortly thereafter, I was accepted as a fellow in neuropathology at the Boston VA along with the title of instructor in neurology at Boston University Medical Center. My dream was coming true!

The Boston years

The neuropathology service at the Boston VAMC was a treasure trove regarding nervous system pathology. Along with my co-fellow, Dr. Ronald Kim, who eventually took a position in Syracuse, we cut 200 brains in 1 year. I saw everything that is to be seen in neuropathology. I became acutely interested in the thalamus after attending lectures by Dr. Paul Yakovlev, a Russian emigree and professor of neurosciences at Harvard University, who had trained with Babinski in Paris in the 1920s.

Pursuing my interest in the thalamus, I reviewed thalamic slides from every single brain cut in our service. One day, I came across a peculiar sight. Reviewing an eosinophilic stain of nerve cells of the dorsomedial nuclei of the thalamus of a patient who had died with myotonic dystrophy, I observed peculiar eosinophilic inclusion bodies in the cytoplasm of most thalamic neurons. A few eosinophilic bodies were also seen in the hypothalamus and in the brainstem. My instructors had no idea what they represented and had never seen anything similar. Reviewing preserved slides from other patients dying with myotonic dystrophy, I confirmed the ubiquitous presence of cytoplasmic eosinophilic inclusion bodies in the dorsomedial nuclei of the thalamus in patients with this condition. I reviewed the literature and found no reference or citation to such lesions. I presented the slides to Dr. Edward P. Richardson, head of neuropathology at the Massachusetts General Hospital, who was a consultant neuropathologist at the VAMC once per month. Dr. Richardson had acquired recent fame after describing progressive multifocal encephalopathy. He reviewed the slides, during which session my pulse was beating at 120/minute, expecting accolades worthy of Lewy or Negri. Eventually, Dr. Richardson looked up, removed his glasses, rubbed his eyes, and said, “They are there; next slide.” In other words, he did not know what those inclusion bodies represented.

The saga to find out what the cytoplasmic inclusion bodies meant had commenced in my career. In 1972, I published a paper titled “Eosinophilic bodies within neurons in the human thalamus: An age-related histologic feature,” suggesting that the cytoplasmic bodies represented a degenerative lesion likely underlying the apathy, cognitive disorders, and hypersomnia presented by patients with myotonic dystrophy (Culebras et al 1972). After all, the dorsomedial nuclei of the thalamus are heavily connected with the hypothalamus and are origin to the orbito-thalamic tracts that intervene in cognition. More research was to come in future years.

Boston was the mecca of neurology. At the Thursday meetings of the Neurology Society, one could enjoy presentations by Derek Denny Brown, Raymond Adams, Paul Yakovlev, Norman Geschwind, Frank Benson, and other iconic celebrities. The sessions were animated with lively, highly educated discussions. Occasionally, sitting in the back of the room, I would raise my hand and, venting more courage than a matador, I would ask a question or make a brief comment. The speaker would always answer with kindness and wisdom, while the big guys in the front rows would look back, projecting a gaze that meant, “Who the h… is that?”

On the faculty At Boston University

Dr. Robert Feldman, chairman of neurology at the Boston University Medical Center, offered me to stay on the faculty as assistant professor in charge of the neurophysiology laboratory at University Hospital. He was impressed by my training in neurophysiology at the Cleveland Clinic under Dr. Charles Henry, one of the EEG pioneers. The EEG laboratory had one bed and one technician, but soon I created a school of EEG technology to increase the laboratory staff. Three young individuals full of enthusiasm applied.

My thoughts kept going back to the cytoplasmic inclusion bodies in patients with myotonic dystrophy and hypersomnia. I had just read that growth hormone was mostly released during deep stages of NREM sleep. I figured that if the thalamus and hypothalamus were damaged, as in patients with myotonic dystrophy, the release of growth hormone at night would be deficient, adding support to the concept that the hypothalamus-thalamus-orbitofrontal lobe axis was damaged, thus explaining hypersomnia. I spoke with my colleagues at Massachusetts General Hospital, but they were not interested in sleep. With the help of my young EEG staff, we devised a polysomnograph based on the Grass equipment at our disposal. Using the Rechtschaffen and Kales scoring manual, we improvised a methodology that produced very decent polysomnograms with three channels for EEG, two channels for eye movement activity, one channel for EMG, and one channel for EKG. This was sufficient to score sleep. We recruited patients with and without myotonic dystrophy from the muscular dystrophy clinic, which was under my direction; thus, we embarked on nocturnal polysomnography, drawing blood samples every 30 minutes for growth hormone measurement. These were the first paper-recorded polysomnograms – between 1972 and 1974 - ever registered in Boston. I conserve some of them in the basement of my home in Fayetteville, NY. Other records were donated years ago to the EEG laboratory at Boston University Medical Center. Dr. Stephen Podolsky, an endocrinologist, agreed to measure growth hormone in samples obtained during polysomnography from our patients with and without myotonic dystrophy. The results showed that, indeed, patients with myotonic dystrophy had no, or very scarce, secretion of growth hormone at night, suggesting malfunction of the hypothalamic-thalamic axis and supporting the notion that hypersomnia in myotonic dystrophy was related to the cytoplasmic inclusion bodies discovered in the dorsomedial nuclei of the thalamus (Culebras et al 1977).

Back to Spain

In 1974, I announced that the Fundación Jiménez Díaz of Madrid, my alma mater, had offered me a position in the neurology service. I accepted and moved with my family and pets to Madrid. We were socially happy, but I was academically deprived. I developed a private practice in neurology but without a chance of engaging in clinical research. In 1977, I decided to return to the United States. My former chairman, Dr. Robert Feldman, alerted me that a position was available as chief of the neurology service at the VAMC in Syracuse, NY, affiliated with the State University of New York, Upstate Medical Center. I applied, interviewed in February while a blizzard was blowing, and accepted to take the position starting in July 1977. My selling points were my training in prestigious centers and my interest in clinical research that I wanted to continue and enhance.

Syracuse

As newly appointed chief of neurology at the VAMC, I applied for a grant in the amount of $10,000 as seed funding to open a research sleep laboratory. The grant was soon awarded by the U.S. Veterans Administration, and I started a sleep laboratory using the existing EEG equipment. In 1977, there were no sleep laboratories in Central New York, and the EEG technicians enthusiastically helped organize and give function to the laboratory. My research was centered on testing the nocturnal secretion of growth hormone, prolactin, and cortisol in patients with various neurologic conditions, including myotonic dystrophy. The research effort resulted in multiple articles published in peer-reviewed journals that attracted the attention of the national neurologic community.

Soon after opening the research laboratory, I started feeling the pressure from the local medical community to evaluate veteran and non-veteran patients with suspected sleep disorders. In the absence of a sleep laboratory in Central New York, patients were referred to sleep laboratories in New York City and Buffalo. I presented the idea of drafting a sharing agreement between the VAMC and the Upstate Medical Center that would allow non-veterans to be evaluated (and charged for services provided) at the VAMC sleep center. The concept was fruitful, and for several years, this was the only resource in Central New York.

The chairman of neurology at the Upstate Medical Center, Dr. Gill Ross, was very much aware of my interest in sleep. I had been appointed associate professor of neurology at inception, and in 1984, I was promoted to full professor, providing services at the Upstate Medical Center. Dr. Ross mentioned that he had a friend at the Montefiore Hospital in New York City, Dr. Elliot D. Weitzman, who was running one of the early sleep laboratories. “Would you like to visit?” “Of course,” I answered, “Will your secretary make travel arrangements?” “No need to,” he answered, “we will fly in my own plane.” And weeks later, I was on my way to New York City, flying in a private plane for the first time. Dr. Weitzman was very friendly and kind, showing us around his two-bed laboratory and explaining the intricacies of developing a sleep laboratory in those early times.

In the mid-1980s, I proposed to the dean of the Upstate Medical Center the idea of opening a sleep laboratory at Upstate. He declined, arguing that there were other priorities, like the intensive care units. Undeterred by this answer, I visited a local private hospital, Community General Hospital, and proposed to the medical director, Dr. Black, the creation of a private sleep laboratory. “It is interesting that you ask. We have a brilliant young attending in Pulmonary who is also interested in sleep. Why don’t you talk to him?” So, I did, and Dr. Robert Westlake and I agreed to present a formal proposal to the medical director. Months later, circa 1987, a private sleep laboratory with two beds was opened at Community General Hospital. For 10 years, this was the busy sleep center of reference in Central New York. Coincidentally, some 15 years later, Community General Hospital was purchased by Upstate Medical University, and the sleep center was moved to another building, increasing to 12 beds. At present, I serve in that new facility as Medical Neurology Director.

My career in sleep disorders expanded during those years. At the University of Alicante in Spain in 1990, I presented a dissertation in Spanish, “Contribución al estudio de la neurología del sueño,” which earned me a summa cum laude doctorate in medicine, an extraordinary prize and PhD equivalent. In 1992, the journal Neurology invited me to be the editor of a supplement titled “The Neurology of Sleep,” which attracted much attention among mostly sleep-naïve neurologists (Culebras 1992). Multiple books, chapters, and journal publications as well as presentations in sleep ensued. Professional associations entrusted me with honors, such as chair of the AAN Sleep Section, chair of the Sleep Research Group of the World Federation of Neurology, co-chair of World Sleep Day of the World Sleep Society, and associate editor of Sleep Medicine. I served as secretary of the AAN for 2 years and, in addition, ministered in this superb organization as chair of various standing committees.

I was able to bind my two professional devotions, sleep and stroke. At the VAMC in Syracuse, I became the principal local director of many clinical research projects in stroke medicine, including NASCET, WARRS, TOAST, WASID, and other national and international studies. In the early 2000s, I served as Founding President of the World Stroke Federation, an organization that later merged with the International Stroke Society to form the current World Stroke Organization. This dual devotion has been reflected in multiple publications, chapters, and presentations dealing with both topics (Culebras 2002).

In 2024, the World Sleep Society (WSS) created the Antonio Culebras Award to distinguish and reward advocates who have organized sleep health awareness activities during World Sleep Day, a WSS celebration that recognizes excellence in the promotion of sleep’s essential role in health.

Epilogue

At present, I spend 8 months of the year practicing sleep medicine at the Upstate Medical Center of Syracuse, NY. The rest of the year I spend in my home on the Mediterranean coast of Alicante, Spain, where, thanks to telemedicine, I continue to follow my New York patients without fail.

I have proudly enjoyed the position of editor of the Sleep Disorders section in MedLink, an appointment that was originally proposed by Dr. Michael Aldrich in 1992.

References

Adams RD, Victor M. Principles of Neurology. McGraw, 1977.

Culebras A. The neurology of sleep. Neurology 1992;42(7 Suppl 6):1-94. PMID 1630634

Culebras A. Sleep and stroke. Continuum. Sleep Disord 2002, 8:119–131.

Culebras A, Podolsky S, Leopold NA. Absence of sleep-related growth hormone elevations in myotonic dystrophy. Neurology 1977;27(2):165-7. PMID 556833

Culebras A, Segarra JM, Feldman RG. Eosinophilic bodies within neurons in the human thalamus. An age-related histological feature. J Neurol Sci 1972;16(2):177-82. PMID 4114005