Interview: Dennis Spencer

Dennis Spencer, M.D., is a tall man with glasses and a thick beard. He laughs easily and looks comfortable in casual clothes, which often include a black leather vest and cowboy boots. The walls and shelves of his cramped office are lined with photographs and memorabilia reflecting his professional interest in the history of neurosurgery and a passion for Harley-Davidson motorcycles. His easy-going manner belies his prominence as one of the foremost neurosurgeons in the country and his position as the Harvey and Kate Cushing Professor and chair of the newly established Department of Neurosurgery. He has been at Yale since 1971, where he has pioneered surgical procedures that have now become standard in operations for treating severe epileptic and other seizure disorders. Shortly before the interview with Contributing Editor Marc Wortman began in the department’s conference room, he had completed surgery on a 10-year-old boy with epilepsy and was awaiting the report from the recovery room.

Could you describe a bit of what you did in surgery today?
We operated on a young boy who has seizures that began in the areas of his brain controlling his left foot and leg and had then spread to the rest of his brain. Initially, we identified on an fMRI scan—functional magnetic resonance imaging—the relative positions of his motor and sensory cortex and then, using a grid of electrodes implanted beneath the skull, determined where the seizures were beginning. After we recorded a number of seizures in the epilepsy unit, we then stimulated between electrode contact points on the grid to more precisely localize movement and sensation—to determine precisely which square inch or so of brain tissue controls them. Then we mapped these regions relative to the area where the seizures begin and where there are cortical developmental abnormalities. Those small sections of the cortex are what we removed during surgery today.

We performed an additional procedure called multiple subpial transection, in which we separate superficial layers of the brain, interrupting the connection so that the seizures can’t spread. Seizures spread across the surface of the brain, or from cortical cell to cortical cell. By cutting these connections with a fine knife underneath the brain’s surface, you interrupt the short connecting fibers and you destroy their ability to communicate. This interrupts the initial spread of the seizure.

In operating on the brain in this way, what sort of risks do you run of causing other problems?
Regarding multiple subpial transections, the risks are primarily when operating in the language association cortex. Transections may cause some difficulties in naming things, but the extent of the loss varies from patient to patient. The younger patients are most likely to regain full function. For example, we have a few-month-old baby in our service right now who has a developmental abnormality of the entire brain. She has seizures that cause her to live in a dazed state. But they involve just one hemisphere, so we will actually remove the back half of the brain. If a baby has a stroke at birth or has developed a bad hemisphere before birth—or in fact any time up until the age of 1 year—all functions can transfer from one hemisphere to the other except for fine finger movement and toe movement. Up until the age of 1, you can transfer language, sensation and cognitive functions completely.

How did surgeons begin to think about cutting open the living brain to treat disorders?
Much of what we understand about the human brain today has actually come from epilepsy surgery over the years. Other than now, I think the time to be alive in the history of medicine would have been the end of the 19th century. Until then, the brain was thought to be a rather homogeneous organ. How do you know how to parcel out a portion of the brain into a specific function or put those parcels together as more complicated functions? Nobody really did. They thought that the brain behaved in a holistic fashion because of animal experiments in which investigators would cut out pieces of the brain and the animal would still function fine. Then the development of electrical stimulation led scientists to stimulate the surface of an animal’s brain. This caused movement on the opposite side of the body, and they found that there was an area of the brain that they could stimulate and elicit the same movement and reproduce the results. For the first time, they began to think about localization of function.

A famous English neurologist, Hughlings Jackson, thought that the effect of electrical stimulation was very much like focal seizures that he had seen in his patients. He thought that it probably represented the same kind of phenomenon that happened when somebody had a motor seizure of the hand, for instance. He speculated that the seizure probably represented a local area of the brain on the opposite side that was diseased and excitable. This is very logical today, but it was a revolutionary concept a hundred years ago. Sir Victor Horsley was the leading neurosurgeon in England at the time. Working with Jackson in the late 1880s, he operated on a patient who had a focal seizure. They had no way of knowing whether somebody had a specific disease of the nervous system and no way of knowing where that disease was located or how to get there. Horsley exposed the suspected motor area of the brain, found the tumor and removed it, and the patient’s seizures went away. That was really the beginning, not only of thinking about surgery for epilepsy and a radical treatment for tumors, but it was also the beginning of learning about the brain and localization of function.

How did neurosurgery arrive at Yale?
Not long after Horsley did his first operation, Harvey Cushing was an undergraduate at Yale. He became fascinated by brain physiology and, after graduation in 1891, went to Johns Hopkins to study medicine. Following up on Horsley’s work, he began to explore neurosurgery in the United States. During his general surgery training at Hopkins, he started the first laboratory for the investigation of neuroscientific issues there. After he finished his training, he went to the Peter Bent Brigham Hospital in Boston, where he spent most of his active career. He removed many brain tumors during his career with a morbidity and mortality rate that rivals modern practice statistics. He’s known in the United States as our father of modern neurosurgery.

Neurosurgery continued at Yale while Cushing was at Brigham. Sam Harvey was the first chairman of the Department of Surgery here in 1924. He had been trained by Cushing as a neurosurgeon, but like all of the early neurosurgeons, he was a general surgeon too. He was the first neurosurgeon to head a general surgery department, however, and so the first surgery department at Yale trained individuals in both disciplines. One of his first students, Bill German, also had spent a year training with Cushing in neurosurgery. Harvey appointed him the first chief of what would become the Section of Neurosurgery.

Didn’t Cushing eventually come back to Yale?
Yes, when he retired from the Brigham in 1934, he came to Yale as a professor of neurology and neurosurgery. He brought everything with him, all of his records and his collection of brains and tumors in bottles. Cushing photographed every patient whom he ever saw. There are 15,000 five-by-seven photographs stored here at Yale. They’re really incredible pieces that document neurological disease and the early days of neurosurgery. Right now, we are procuring resources to again preserve all of the brains and to archive the photographs and to get them safely put away in a museum-like surrounding. The collection is housed in the John Fulton House, a mansion just outside New Haven that is provided by the Axion Foundation to the medical school library. Cushing was a bibliophile as well. He and Fulton, who was a famous physiologist at Yale at that time and a good friend of his, put their book collections together and began what is now the medical library’s world-renowned historical library. They also started the first journal in the field here at Yale, The Journal of Neurosurgery, which is still our principal academic journal.

Bill Collins came to Yale in 1967 as the second chief of neurosurgery and put true academic credibility into the program. He began the process of subspecialization within neurosurgery, started a basic laboratory in the study of pain, and obtained the first spinal cord injury grant, which is still ongoing in the department. I came as a resident in 1971 and became a faculty member in 1977. Ten years later, I became chief of the section.

The section of neurosurgery separated completely from the Department of Surgery last year and became a free-standing department. Why did that happen?
Departmental status has historically emerged from a specific discipline’s academic maturity. The ways of treating and researching nervous system disease has wandered far from general surgery principles and stands more as an interdisciplinary field, sharing a knowledge base primarily with the basic neurosciences, neurology, psychology and psychiatry. Our section had received national and international recognition in clinical and basic neuroscience, NIH funding, for example, growing 10-fold over a 10-year period. Our vision, therefore, required more freedom to form the interdisciplinary programs essential to caring for patients with diseases of the nervous system. Thus, with solid support by the Department of Surgery and the academic and clinical deans, we became a department in January of 1997.

Subspecialization seems to be an even more important professional pathway in neurosurgery than other specialties. Why is that?
It’s clear that patients gain the most and do the best with individuals who do the same technologically difficult things every day. Subspecialization is a natural evolution in neurosurgery, which seems so sub-specialized in itself, yet is enhanced when concentrating on subdivisions of the very complicated nervous system.

Your subspecialty is epilepsy. How has that developed as a field?
The study and treatment of epilepsy have much of their origins here at Yale, in the late 1960s and 70s. One of the first epilepsy monitoring units in the world was established by Richard Mattson at the VA hospital in West Haven, where cameras were placed to study the behavior of patients, coupled with electrodes that had been locally constructed and then implanted in the brain. We could then watch a spontaneous seizure and correlate that with the electrical source. We began to identify that in certain of these patients we could find scars, tumors, vascular lesions and other abnormal areas that were sources of seizures.

Magnetic resonance imaging, or MRI, came along in the mid-1980s. Early on, we adapted the computer to our imaging systems. Two Yale undergraduate students worked with Greg McCarthy and me to design the first computerized imaging work station anywhere in neurosurgery. We wished to replace our old system, which was based on plain X-rays coupled with injecting air into the brain’s fluid cavities and dye localization of cerebral arteries. Combining stereotaxy with the MRI using the computer, we could then create a virtual image of where our electrodes were to go along specific trajectories within the brain. MRI also allowed such detailed anatomical views of the brain that more subtle brain developmental abnormalities could be viewed as easily as the more discrete lesions, such as tumors and vascular anomalies.

We’ve made enormous advances since then. Now, we can see epileptogenic developmental and atrophic areas of brain. Many patients no longer even have electrodes implanted at all. They can have an image correlated with scalp recordings and then go directly to surgery. It all goes back to what we talked about originally, localizing function of the brain. Now we have better localization techniques, but electrical stimulation has remained the best technique for identifying brain function. It’s not very long ago, 1978, that we were injecting air into people’s heads to identify structures and to help place homemade electrodes. Boston has a computer museum in which our original operating room from the 1970s has been set up to illustrate the first utilization of computers to localize function in brain surgery.

What attracted you to work on epilepsy?
Epilepsy surgery is my passion. I spend all my clinical and research time with these patients. Epilepsy affects one percent of the population. It’s a chronic problem, primarily in young people. It destroys their lives. They can’t work, they can’t drive. Often, it destroys their socialization, so they don’t establish normal relationships and often don’t get married, maintaining dependency on their families. It’s estimated that there are 250,000 to 300,000 patients in the United States who could be helped with the surgical treatment of epilepsy. This is a group of patients in whom you can identify the source of the seizures and, by removing it, can cure their epilepsy. You may cure epilepsy overnight. It is the only chronic disease that can be cured in the operating room.

Imaging is an increasingly important part of neurosurgery. What are its advantages?
Imaging is absolutely critical for growth in neurosurgery right now. We’re still in an experimental stage. Jim Duncan, senior physicist in the Department of Diagnostic Radiology, and I have formed the Laboratory of Image-Guided Neurosurgery. It brings together the investigators from spectroscopy, functional MR, neuropsychology, linguistics and physicists to provide graphic analysis. Through interdisciplinary methods, we can enhance learning about brain functions and real-time imaging during brain surgery. We’re still at the beginning of what we envision as a long-term collaboration. We are combining the MR image with measurements of the brain in the operating room so that we can more precisely predict dynamic changes during brain surgery. We can do a variety of anatomical, metabolic and functional localizations that were never possible before. We need to superimpose all of those images and data when we go to the operating room so that we know what to resect and how to operate without harming critical brain structures. The purpose is to make neurosurgery safer and less invasive. You can minimize cranial openings if you know your position precisely before you have to open the skull. That greatly decreases morbidity and costs.

What’s on the horizon for neurosurgery?
We think that regional brain perfusion of drugs or genes or stimulation is going to be the next step for delivering treatment to patients. One of the problems with drug treatments for nervous system diseases is that drugs are relatively non-specific in many instances. Drug treatment of a convulsive state slows the entire brain. Not only does it help suppress the seizure focus, it suppresses many normal activities. Now that we’re able to localize diseases within regions of the brain, our next step is to develop a probe system that will allow us to sense and measure biochemical changes, and then to provide focused, measured delivery of therapies. It may be delivery of genes or drugs or electrical stimulation for instance, but through an implantable source that is varied and that doesn’t require being connected to the outside. We’re working on such a device that can regionally deliver these drugs without affecting the rest of the brain. Then the next step might be to deliver a gene that will help regulate that cell so that it would behave itself.

Your wife, Susan Spencer, is a neurologist. It is interesting that you two work together so closely.
Yes. We both began our work at about the same time. For 20 years we’ve been publishing papers together. She is the medical co-director of the epilepsy program and now the director of the monitoring unit that we have in the hospital. In fact, beginning July 1999, she’s the next president of the American Epilepsy Society. She sees most of the epilepsy patients when they come in and establishes who needs new drugs and who may be a candidate for surgery. We have a two-hour conference in the Department of Neurosurgery every Monday afternoon, to which we bring patient histories and their relatively complicated evaluations involving PET and SPECT scans and readings from depth electrodes and such. We have about 25 people who come representing psychiatry, neuropsychology, neurology, etc.

You’ve got what sounds like an incredibly demanding life, between the stress of surgery and the demands of research and running a major medical department. How do you manage?
On the back of a Harley, a hog. Dr. Greer, Charles Greer, the department’s vice chairman for research, and I spend occasional Sunday mornings terrorizing the Connecticut countryside.

You drive a motorcycle? That’s not the typical image of a brain surgeon.
No. I recently gave a talk to the Hospital’s Board of Trustees, where Joe Zaccagnino [President and Chief Executive Officer of Yale-New Haven Hospital] introduced me to this roomful of prominent officials, as the Harvey and Kate Cushing Professor of Neurosurgery, chairman of the department and so on. Then he added that I was the only person who showed up at our hospital retreat in full leathers on a Harley. It was really not the introduction that I expected. My love before Harleys is actually my children, the mystery and wonder of raising them—and water lilies. I have two ponds, and in the summertime what I like to do is gardening—gardening and riding hogs.

As a brain surgeon, you deal with the core of what makes us humans and individuals. That must be a heady experience.
Neurosurgeons have a tendency to be prima donnas because of what they do, but the residents we train and the patients we treat do more to humanize us than anything else. The patients whom we take care of, in my case, the epilepsy patients, make us focus on giving back health. We all become more human in the process. We have the smartest and most talented resident staff of any neurosurgical department in the country. Every time you make a clinical decision or touch a patient, the headiness disappears and is replaced by the responsibility of mentoring the next generation and helping another person in grave need. You cannot be selfish and do that job well. YM