ON THE FRONTIERS OF DEEP
Neurologist Anette V. Nieves, MD, the newest member of The Center for Movement Disorders at UMDNJ-Robert Wood Johnson Medical School (RWJMS), has a videotape of herself alongside patient Jack Goldman during his deep brain stimulation (DBS) surgery on February 22. You can see her talking to him, patting and instructing as Richard Lehman, MD, associate professor of neurosurgery at RWJMS, works to position a piece of hardware that will adjust what 18 years of Parkinson's disease has done to the man's neural network. Says Nieves, "I hold hands, tell patients they are doing fine and that they need to hang in there." Lehman agrees, "She's there until we are ready to close up at the end."
The operating room scene on any given journey into the brave new world of DBS is a pretty amazing, and possibly scary, place. A stereotactic frame, or halo, was attached to Goldman's head mechanically through the skin and then the frame itself was bolted to the operating table. In order for Lehman to drill holes carefully into the brain, about five inches up from the eyes on both sides of the head, the patient had to be immobilized, which was difficult because he had been off the very medication which controls his movement disorder since midnight. There can be no drug interference at certain stages of this surgical journey. Keep in mind that patients like Goldman need to be awake, too. Doctors a neurosurgeon, neurologists, support players and a biomedical engineer mathematically plotting a high-resolution, three-dimensional path using computer technology must search for the right spot deep inside the head to implant little electrodes connected by wires which will snake from inside and down, behind the ears, to battery packs positioned beneath the skin under the collarbones. Yes, they call this "awake surgery." Only part of it is done under general anesthesia.
Imagine putting yourself there, on that table, and remember that it is up to you to tell the neurosurgical team what you are experiencing. Could you stand it? What would make this experience tolerable?
The answer is complicated, of course, with a very sick patient's decision playing a huge role. An opportunity to live without symptoms tremor, bradykinesia (slow movement), rigidity, postural instability, excess saliva, decreased vocal volume, dystonia of the feet and maybe even loss of sense of smellcan be a powerful motivator. Yet, within your ability to push yourself through such a nightmare are other factors to be found at both RWJMS, where deep brain stimulators (DBS) are being implanted in patients with Parkinson's disease, and New Jersey Medical School (NJMS), where the procedure is done for multiple sclerosis and essential tremor.
Nieves, an assistant professor of neurology, and the movement disorders team have a relationship with patients like Goldman that goes beyond the operating room. Apart from Lehman, the group, including Nieves, has Jacob I. Sage, MD, director of the Center, Lawrence I. Golbe, MD acting chair of the neurology department, neuropsychologist Carolyn Grace, PhD, assistant professor of neurology and Margery H. Mark, MD, associate professor of neurology. The Center is officially designated as the Richard E. Heikkila Advanced Center for Parkinson's Research of the American Parkinson's Disease Association (APDA), named in memory of the first director of their basic science laboratory. Goldman became one of this Center's 3000 patients five years ago. Recently, when he was determined to have DBS done somewhere because his condition had worsened, he told Mark, "You bought me five years of life. I owe you everything." She hugged him and answered, "All I did was adjust the medications." She also informed him that he could have DBS surgery at Robert Wood Johnson University Hospital because they had just received approval from the Food and Drug Administration (FDA) in January for Parkinson's. Though DBS had been done for essential tremor, the official sanction for Parkinson's had just been given. Goldman also had all the right requirements to become a candidate. (See sidebar, page 31, Getting A Green Light for DBS.) "With Dr. Anette Nieves here, the timing was perfect," Mark says.
Nieves is a University of Puerto Rico graduate who did her neurology residency at UMDNJ's University Hospital (UH) and Robert Wood Johnson University Hospital from 1996-99 and was then encouraged by her professors to pursue a fellowship at the University of Toronto, Canada, which has the largest surgical program for movement disorders anywhere. On completion, she was enticed to return to New Jersey last July to head the Parkinson's surgical program, but not before turning down an offer to become director of surgical services there in Toronto. Everyone is happy she's back and according to Mark, in order for neurostimulation to succeed, you need exactly what Nieves brings. "Pre- and post-op evaluations are essential. Patients need to be chosen and followed up properly, monitored regularly and programmed correctly. It's not just a question of putting the electrodes in."
This (DBS) technique originated in Grenoble, France, and since 1997, more than 14,000 patients worldwide have received the Activa Tremor Control System, designed by Medtronics. The device itself has several parts including the deep brain stimulation lead, an insulated wire with four electrode tips which can be implanted in the thalamus, the subthalamus nucleus (STN), or the globus pallidus internal segment (GPi) to inhibit the overactive cells damaged by disease. An extension wire is connected to a pulse generator, which is positioned just under the collarbone and is similar to a heart pacemaker which provides electrical pulses. Connecting DBS electrodes by wire within the skull to these battery packs is the surgical step done under general anesthesia.
Bilateral DBS, or surgery on both sides of the brain the same day, helps control movement and muscle function on both sides of the body and is recommended for Parkinson's. In unilateral, or single system implantation, the side of the brain controlling the most severely affected limbs, on the opposite side of the brain, is usually chosen. A hand-held magnet is also part of the package and with it, the person can turn the stimulator on or off. Strolling through an airport security screening machine or a shopping center anti-theft scanner, theoretically, can tweak the components off their settings. Eventually however, by adjusting this electrical circuit, the stimulator can be manipulated to suit the patient. There are four ways to set the program through stimulation poles, frequency, pulse width and voltage and each can be tuned separately.
"It's a long day of eight or nine hours," says Michael Schulder, MD, associate professor of neurosurgery at NJMS, describing DBS, his favorite surgery. "Not all of this time is uninterrupted in the operating room but most people have a limit to how long they can tolerate it. Pain in this surgery is not the main problem, however. The brain feels no pain. Probably the hardest part for the patient is staying awake but nearly immobile for most of it." Yet, having that person consciously on the team is critical. "I go in knowing within millimeters of where I want to place the electrode but my goal during surgery is to narrow it down to less than that. You need to have physiological confirmation that the electrode is ending up in the right spot."
Major complications are a statistically negligible risk and at this point in time the electrode itself inside the brain has no effect on nearby tissue. There is a one to two percent risk of bleeding in the brain, which can occur without symptoms and cause a stroke. However, French doctors, who have been experimenting with DBS since the late 1980s, have tracked recipients and report that tremor, bradykinesia and rigidity can be reduced up to 50 percent. In the meantime, the FDA has also ordered the manufacturer, Medtronics, to study longterm effects of constant electrical brain stimulation. Schulder is optimistic and believes that DBS, "is a huge advance in neurosurgical technology and a procedure which provides real functional improvement for so many people."
Batteries do have a way of running down within three to five years, but can easily be replaced. In fact, Schulder just did his first neurostimulator battery replacement in March on an essential tremor patient, 77-year-old Viola Thornton, who was a DBS recipient in 1999. She's one of his happy endings. A woman who couldn't even cut her own food because of uncontrollable shaking, she's been sewing, knitting and enjoying her large family in Belleville. The new battery was no big deal.
Recovery is almost immediate, according to Schulder, whose patients go home in a day with nothing more than a little soreness at the incision sites. Jack Goldman was "one happy camper, dancing around" right away, Mark says, cautioning that "not everyone gets this kind of a response. It's important that patients realize that surgery is not a cure and conditions may change."
Yet, subtle adjustments to the system can be made any time, which pleases surgeons. In the past, Lehman used a heated probe to destroy abnormal brain cells in a procedure called a pallidotomy, to improve life temporarily for some movement disorder patients. "Those were destructive lesions and once you did it, you couldn't reverse it," he says. Whereas, "with stimulating electrodes, you can always modulate the current, turn it off or in the most radical case, go back and reposition the electrode." Lehman believes that DBS is a tool which will remain in the hands of neurosurgeons for at least the next five to ten years. On the horizon, in conjunction with advances in genetic engineering, he sees a time when it will be possible for brains cells to be restored or protected. Mark agrees, "What's down the line is a time beyond surgery and the next new pill. Ultimately we want to get to the root of what causes these disorders and the more we learn about Parkinson's and other neurodegenerative diseases, the more they overlap. All of them are more related than we once thought."
For weeks after Goldman's operation, Nieves continued to fiddle constructively with his programming. "It's like art," she admits, pointing to her programming suitcase which looks like a laptop computer with extra gadgets and dials. On her arrival at RWJMS last year, she was presented with the gift of a new, old-fashioned doctor's bag for storing gear. Neurologists have lots of tools and tricks, she laughs. "I fine-tune. I adjust here, adjust there. You know, the cells talk to one another in the brain. In the operating room, that's how you can tell where you are. They talk to one another and I listen. When I told Jack Goldman that his left foot was just not quite perfect, he said, 'I don't have to be perfect.'"
Yet, perhaps if perfection can be defined as a feeling, that is exactly what doctors like Nieves, Lehman, Schulder, Mark, and their respective teams, receive in return when patients like Goldman say, "Surgery was long. It was scary and at times painful. I could hear a vacuuming inside my head. Yet, I have my relationships back with my kids, with my grandchildren, with my wife. This Parkinson's takes away a lot more than your ability to move. Slowly, my life is becoming richer and richer instead of poorer and poorer." And, isn't that exactly what doctors on the frontiers of DBS want to hear?
The magazine of the University of Medicine and Dentistry of New Jersey