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Professionalism-Autonomic Disorders
David S. Goldstein, MD, PhD: He Could Have Been a Cartoonist. He Became an Expert in Autonomic Disorders Instead.

ARTICLE IN BRIEF

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DR. DAVID S. GOLDSTEIN: “That was probably my biggest discovery; there is just as much of a loss of norepinephrine and the sympathetic nerves in the heart in Parkinsons as there is a loss of dopamine in the dorsal putamen. Since then Ive been trying to figure out the link between the loss of these nerves in the heart and the loss of dopamine terminals in the brain.”

David S. Goldstein, MD, PhD, discusses the trajectory that took him from a potential career as a cartoonist to become a worldwide expert in autonomic disorders in neurology.

While still an undergraduate at Yale University in the late 1960s, David S. Goldstein, MD, PhD, completed his first study of autonomic function. But Goldstein had no intention of pursuing medicine. His goal since childhood was to become a cartoonist.

With a cartoon-illustrated column running regularly in the Yale Daily News, he put together a portfolio and visited Will Elder, the legendary cartoonist for Mad magazine and other national publications. Elder looked over Goldstein's drawings and said he thought the young man could make it as a professional.

“But I wouldn't recommend it,” Elder said.

“Why not?” asked Goldstein.

“Well, I can see from what you have here that, for you, it's all just so much fun. But if you have to depend on this for your bread and butter, it's going to lose its appeal, you're going to have to make compromises and meet deadlines, and the fun will be gone. But you're a bright kid. Why don't you become a doctor? Then you'll be rich, and you can pursue cartooning as a hobby.”

Goldstein decided to follow Elder's advice, becoming a physician and researcher whose pioneering studies — including his discovery of cardiac sympathetic denervation in Parkinson disease — earned him this year's Irwin Schatz Award for Autonomic Disorders at the AAN Annual Meeting. But having spent his entire career at the National Institutes of Health, he has hardly become rich — unlike the other cartoonist at the Yale Daily News at the time: Garry Trudeau, who went on to create Doonesbury.

“There's the irony,” Dr. Goldstein said with a laugh. “He's rich and what about me? I work for the government. I have to make compromises and meet deadlines. And I was the better cartoonist!”

EARLY RESEARCH

Goldstein's first study, conducted while he was still an undergraduate, revealed his ability to ask simple but profound questions about the function, and dysfunction, of the autonomic nervous system. He and a friend, David J. Fink, MD, FAAN (chair of the department of neurology at the University of Michigan), were both taking an intensive program in psychology for which they had to conduct an experiment. A prior study had shown that people placed in emotionally provocative settings who are given false feedback indicating an increased heart rate report a more intense emotional reaction.

“The question that David and I asked was what happens to your true heart rate when you are given that false heart-rate information,” Dr. Goldstein said. “So we measured people's actual heart rates and found that when their false heart rates changed in the setting of an emotional experience, their actual heart rates changed too. After that I became very interested in how the brain and stress affect the heart via the autonomic nervous system.”

He earned a joint MD-PhD in behavioral sciences from Johns Hopkins, and then trained in internal medicine at the University of Washington. To fulfill his required rotation in an outpatient clinic setting, he worked in a cardiologist's office.

One day while accompanying the cardiologist during rounds at the nearby hospital, they examined a stroke patient in the ICU who had what Dr. Goldstein describes as a “bizarre” electrocardiogram.

“We see that with bleeding inside the head sometimes,” the cardiologist told him. “You can get bizarre EKGs that are thought to be related to heart damage.”

Dr. Goldstein wondered which came first: the stroke or the unusual electrical activity in the heart?

“I don't think anybody knows,” the cardiologist replied. “You should study that.”

So he did. Putting aside his outpatient clinic work, he obtained the charts of some 300 patients, half of whom had been admitted for a stroke, but all of whom had had an outpatient EKG prior to admission. He found that 20 percent of the stroke patients had pathologic Q waves, and 26 percent had left ventricular hypertrophy, but that those findings were not new at the time of the stroke. In a paper published in Stroke in 1979, he was the first to report which EKG findings are new at the time of a stroke.

By the time his study was published, in 1979, he had been accepted by the National Heart, Lung, and Blood Institute to spend his third year of an internal medicine residency as a clinical associate in the intramural research program. In a meeting with Harry Keiser, then chief of the Hypertension-Endocrine Branch, Dr. Goldstein talked about his interest in how emotions and stress affect the heart.

“That's all well and good,” Dr. Keiser told him. “You have interesting ideas, but I have one question for you: What are you going to measure? Science is measurement. It's not theories. It's data. I don't care what you measure, but you have to measure something.”

As Dr. Goldstein recalled, “That was really an eye opener. He was right. I picked catecholamines, like adrenaline, and set up an assay for measuring them. It was the first validated method for measuring norepinephrine and adrenaline in human plasma by high-pressure liquid chromatography with electrochemical detection.”

His next novel measurement was the development of fluorodopamine positron emission tomography scanning to visualize the sympathetic nerves of the heart. Seeking to test the hypothesis that hypertension might be caused in part by excessive cardiac innervation, he ended up discovering that people with Parkinson's have the opposite problem: sympathetic noradrenergic deficiency.

“That was probably my biggest discovery; there is just as much of a loss of norepinephrine and the sympathetic nerves in the heart in Parkinson's as there is a loss of dopamine in the dorsal putamen,” Dr. Goldstein said. “Since then I've been trying to figure out the link between the loss of these nerves in the heart and the loss of dopamine terminals in the brain.”

He joined the National Institute of Neurological Disorders and Stroke in 1990 to establish the Clinical Neurochemistry Section and then the Clinical Neurocardiology Section, which he is in the process of renaming the Autonomic Medicine Section, to reflect his interest in all types of dysautonomias, not just those affecting the heart.

“Dysautonomias are common, debilitating, insufficiently understood, and poorly researched,” he said. “They are largely invisible in traditional academic circles, despite what I think is an epidemic of interrelated functional disorders involving altered functions of components of the autonomic nervous system, including chronic fatigue syndrome, chronic orthostatic intolerance, postural tachycardia syndrome, pseudopheochromocytoma, neuropathic pain, and even migraine.”

Heartened by the recent establishment of an autonomic disorders certification by the United Council for Neurologic Subspecialties, Dr. Goldstein noted that he will be leading a course for interested neurologists at the 2018 annual conference of the American Autonomic Society in October at Newport Beach, CA.

Having authored more than 575 research articles and such books as The Autonomic Nervous System in Health and Disease and Principles of Autonomic Medicine (the latter available as a free ebook), Dr. Goldstein still enjoys cartooning when he isn't enjoying time with his wife of 46 years, their five children, and 17 grandchildren — probably a heck of a lot more than Garry Trudeau has.

LINK UP FOR MORE INFORMATION:

•. Goldstein DS, Holmes C, Cannon RO 3rd, et al. Sympathetic cardioneuropathy in dysautonomias https://www.nejm.org/doi/10.1056/NEJM199703063361004?url_ver=Z39.88-2003. N Engl J Med 1997;336(10):696–702.
•. Goldstein DS, Robertson D, Esler M, et al. Dysautonomias: Clinical disorders of the autonomic nervous system http://annals.org/aim/fullarticle/715764/dysautonomias-clinical-disorders-autonomic-nervous-system http://annals.org/aim/fullarticle/715764/dysautonomias-clinical-disorders-autonomic-nervous-system. Ann Intern Med 2002;137(9):753–763.