Probing Minds

Dec 31, 2000

Northern Ohio Live Magazine, January 2001

by Anton Zuiker

Over the cackle of static, Amed Hammoud whispers to me through his surgical mask, “This is the frontier of medical technology.” Hammoud, with a Ph.D. in biomedical engineering, works for Medtronic Corporation. This snowy morning in December, he is in operating room #11 at the Cleveland Clinic Foundation, operating the Silicon Graphics computer and Medtronic’s software that is allowing Clinic neurosurgeons Ali Rezai and Erwin Montgomery to ever so slowly push an electrode the size of a hair deep into the brain of Russell xxxx. This, the frontier, is called deep brain stimulation, or DBS.

DBS is a relatively new surgical treatment for movement disorders such as Parkinson’s disease, epilepsy and multiple sclerosis, which can cause immobilizing tremors in a person. (“It’s as if you’re driving with the parking brake on,” says Rezai.) The Clinic has embraced the DBS procedure, and the doctors in the room today are a good part of why Hammoud also whispers to me, “The Clinic is the leading center for DBS in the U.S.”

Russell, a construction worker from West Virginia, has multiple sclerosis; his case is more difficult than the Parkinson’s cases that Rezai has mastered, but the procedure is the same. The surgical team will find the sweet spot in area of the brain called the subthalamic nucleus that, when stimulated with the electrode, will shut down and stop the tremors.

That noise filling the operating room is the key to the surgery. It isn’t white noise to help the patient sleep – Russell is awake and responsive – it’s actually the sound of Russell’s brain. What sounds to me like AM radio static mixed with Morse code is the conversations of neurons sending electrical signals back and forth. This is a dialogue that Montgomery eagerly follows, for he’s learned that translating the signals will pinpoint where in the brain the electrode is resting. “It’s like travelling from Eastern Europe to Western Europe along a highway,” says Montgomery. “First you hear Polish, then you hear German.”

Montgomery first heard the sounds of brain cells in the laboratory of Nobel laureate Sir John Eccles, neurophysiologist. “I just thought that was the coolest thing I’d ever heard, and I decided that’s what I wanted to do.”

Keep travelling on Montgomery’s highway and you’ll make it to Grenoble, France, where the father of DBS, as Rezai calls him, teaches neurosurgery. In surgical procedures called pallidotomy and thalamotomy, surgeons destroy parts of the brain to stop tremors. During those procedures, the surgeons use an electrode to find the correct area to treat. In 1987, professor Alim-Louis Benabid, M.D. noticed that this stimulation of the thalamus mimicked the effect of the destructive surgery. So he developed DBS.

Last summer, Benabid agreed to serve as consultant staff member to the Cleveland Clinic Neurological Surgery Department, where he visits two weeks out of the year. Which is why he also is here in operating room #11, peering at Hammoud’s computer.

Rezai and Hammoud eagerly demonstrate how the software morphs a CT scan with an MRI picture, with an overlay of topographical lines, into a 3-D image of the brain, giving the surgeons a literal road map to Russell’s thalamus.

“The thalamus is the Grand Central Station of the brain,” Rezai had told me earlier. It’s this small area at the center of the brain, divided into 120 subregions, that routes the body’s signals to move. Rezai expects that the electrode he implants in Russell’s thalamus will “quench the chaotic neuron activity” that makes him twitch and quiver. DBS, says Montgomery, is like discovering your car has run out of gas, and you can precisely pour a bit of fuel into the carburetor to get it going again. Thalamotomy, he counters, is like pouring gas over the entire car, hoping that some will find its way into the carburetor.

The electrode implanted into the brain will be connected to a pacemaker-like stimulator, the size of a flat pager, that will be sewn into the patient’s chest. This stimulator, worth $10,000, will modulate abnormal brain activity. In some patients, the stimulator is constantly on. In others, the patient can activate the stimulator with a magnetic card when he feels a tremor beginning. Soon, says Rezai, a patient using a modem and the Internet will be able to have his physician finetune the stimulator wherever the physician may be.

“The results are so sudden and obvious once you turn the stimulators on,” says Marc Mayberg, M.D., chairman of the department of neurosurgery. “In my mind, this is a watershed time in the field of neuroscience. It represents the first time physicians have been able to improve or restore neurological function.” DBS, in restoring the freedom of movement to patients, is revolutionary because it is also reversible and does no damage.

And there’s another benefit, says Montgomery. “What is clear in Parkinson’s patients is that there is a long-term benefit that we can’t explain just by stimulation. Patients are much better one month after implantation of the stimulator than they were prior to surgery. The results are incredible. But they’re better at two months than they were at one month. They’re better at three months than at two months.” Something is affecting the degenerative process, he says, admitting that these neurosurgeons don’t know what makes DBS work, but they do know it helps the patients.

Less than a mile away, research scientist Warren Grill is trying to find out why. “We’re taking a step back and addressing a fundamental question,” says Grill, who holds a Ph.D. and is Elmer Lindseth Assistant Professor of Biomedical Engineering at Case Western Reserve University. He’s also the director of the Cleveland Functional Stimulation Center, a consortium of local medical centers that’s brought together the Clinic, Case Western, the Louis Stokes Cleveland VA Medical Center and MetroHealth Medical Center to share research and clinical experience regarding new brain therapies.

Grill received a $1.6 million 5-year grant from the National Institutes of Health to answer his fundamental question: Which neuronal elements are affected by the stimulation – primarily the local neuron cells touched by the electrode, or the passing axon output flowing between those cells? He uses computer-based models to do his testing, and relies on Dr. Montgomery’s clinical research to corroborate the computer. Once Grill and Montgomery determine which neuronal elements are affected by the stimulation, they’ll work on the technology of the stimulation. “Not new technologies for placing the electrodes in the brain,” says Grill, “but making the clinical procedure less reliant on the precise location of the electrode.” He foresees developing new shapes for the electrode, as well as discovering a new wave form for the electrical pulse that does the stimulating.

Sixty-seven-year-old Rudy Mueller is one of those patients who is walking because of the current techniques. Before his August 1999 DBS surgery, Parkinson’s disease had reduced him to crawling around on his knees. He took up to 50 pills a day to treat his tremors. “My life would be at the end now,” he says. With DBS, he’s able to walk with a cane, and even drive himself around his Seven Hills neighborhood. “Now, with my stimulator, I have no shaking whatsoever.” He takes only a handful of pills these days, and he’s grateful that his insurer, Kaiser Permanente, had referred him to the Clinic and paid for the expensive surgery.

“The hope is that all doctors will be as comfortable prescribing electricity as they are prescribing medication,” says Montgomery. Rezai expects that any day now the FDA will grant final approval to DBS as a standard treatment for Parkinson’s tremor. Other emerging areas for DBS use are epilpesy, chronic pain and obsessive-compulsive disorder.

In June 2001, Cleveland will host the international symposium Functional and Restorative Neurosurgery: Defining the Future. “Fifty of the world’s leading authorities and pioneers on neuromodulation – the All-Stars – will be here for three days,” says Rezai. “It will be exciting to bring these minds together to chart the course of neurosurgery.”

One possible innovation, says Mayberg, is a “radical online collaboration to share data intraoperatively, in real time. Dr. Benabid has a grant from Telecom France. He’d be online with a video link and would be looking at the same information on his computer. It may be farfetched, but someday he might even drive the movement of the electrode. As the technology expands, we may become a center for doing operations around the country.”

And then, probing minds will listen in as the brain talks.

Anton Zuiker ☄