For Parkinson’s patients, a surreal brain surgery offers new hope

Larry Clift, 74, of Chattanooga, lies on an operating table with a sheet of plastic draped across his forehead, nearly splitting the room in two. On one side, bright lights illuminate a dime-sized hole in the top of Clift’s skull, surrounded by a white ring of exposed bone and a small ooze of blood. If you look closely, you can see his brain.

But, on the other side of the plastic, Clift is wide awake, eyes open, squeezing a stress ball with his right hand and chatting with a doctor in a white lab coat. She uses small talk to keep him calm while checking that his speech isn’t slurred, which would be a sign that the surgery has gone wrong.

“It’s a sunny day in Nashville,” says Dr. Kisha Young, encouraging Clift to repeat.

“It’s a sunny day in Nashville,” he says back. His voice is weak but clear.

It’s a Tuesday morning in August, and Clift is mid-surgery at Vanderbilt University Medical Center, recently ranked one of the best hospitals in the country. For eight years, he has suffered from Parkinson’s disease, a disabling condition that has made his body stiff and weak. Relentless tremors have taken over his right arm, and doctors are certain they will spread to his left if they do not intervene.

This operation, as surreal and terrifying as it may sound, is supposed to help. During four hours of surgery, a team of doctors place a tiny electrode deep within Clift’s skull, where electric shocks can stimulate the portion of his brain at the root of his disease. If the procedure works, his symptoms will fade with the flip of a switch. And maybe — just maybe — his tremors will never spread to his left arm at all.

“Any time you have tremors,” Clift says, as doctors tinker inside his head, "and the shaking goes away, that’s a miracle.”

Clift was a recipient of deep brain stimulation surgery, which for two decades has been used as a last-resort treatment for patients with Parkinson’s disease, an incurable, degenerative condition that affects millions of people worldwide. But a new decadelong surgery study at Vanderbilt offers a glimmer of hope for younger Parkinson’s patients. Although still far from a cure, the surgery study provides some of the first evidence that any medical treatment can slow the progression of tremors, the signature symptom of the disease.

“We’ve gotten a signal from our early study that is super exciting, but what we don’t know is if it's real yet,” said Dr. David Charles, Vanderbilt's vice chair of neurology, who led the research. “Now it will still take a big study to answer the big question — is this really slowing the progression of the disease?”

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Deep brain stimulation, or DBS surgery, which was approved by the Food and Drug Administration in 1997, is traditionally used to treat late-stage Parkinson’s patients whose condition has progressed to the point where symptoms can no longer be controlled by medication alone.

Patients must be awake during the surgery, often tossing a tennis ball, so they can provide moment-to-moment feedback about their symptoms while doctors place the electrode inside their brain. In concept, the procedure is similar to having your vision tested by an optometrist, but only if your new eyeglasses were being implanted deep within your skull.

The surgery is also exceedingly delicate and small. DBS electrodes are as thin as angel hair pasta and they stimulate a portion of the brain — the subthalamic nucleus — about the size of a black-eyed pea. That nucleus is within a centimeter or two of portions of the brain linked to vision and speech, so a surgeon's mistake could be devastating. To find the perfect spot, doctors use a needle-like sensor that is so delicate it can detect a single electrode firing. In a poetic sense, it can hear the sound of thought.

Vanderbilt doctors famously performed the DBS surgery in 2008 on legendary bluegrass musician Eddie Adcock, who had mostly lost his ability to play due to tremors. Adcock plucked on a banjo during the operation, and at the moment his playing improved, doctors knew the electrode was in the right spot.

“It was the most amazing thing I’d experienced in my life,” Adcock told The Tennessean in a recent interview. “As soon as they hit the sweet spot, I said ‘Stop right there,’ and I could play.”

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The Vanderbilt study, published in July by the American Academy of Neurology, has used the DBS surgery in a new way. Instead of waiting for Parkinson’s symptoms to worsen to a severe stage, doctors implanted electrodes in 14 early-stage patients before they would normally qualify for the surgery.

These participants were then brought back to Vanderbilt for a weeklong observation every six months for 2½ years. During each visit, they turned off their electrodes and stopped taking their medicine, allowing the doctors to measure their tremors at their worst.

Those weeks were grueling and selfless, the researchers said, but the results were promising: When compared to the patients with DBS electrodes, Parkinson's patients who were treated purely with medication were more than 2½ times more likely to have their tremors worsen significantly and about seven times more likely to have tremors spread to a previously unaffected limb.

Mallory Hacker, a research assistant professor at Vanderbilt who was the lead author of the recent study, first discovered the impact on tremors.

These findings are remarkable for a study that was once considered too risky to go forward at all. Charles said the DBS study was initially controversial because of the inherent danger of brain surgery, and the belief that patients were going under the knife years before it was justifiable by conventional medical wisdom.

When the study began, nine out of every 10 Parkinson’s experts were against it, Charles estimated.

“We suffered some pretty harsh criticism. But now, the pendulum has swung the other way,” Charles said. “Now, 17 of the best centers have joined us, wanting to take this next step.”

That next step is a much larger study, designed to confirm the results found at Vanderbilt. The FDA recently approved a clinical trial with about 280 patients spread across 18 medical centers.

Participants must have had Parkinson’s disease for more than one year but less than four. All participants will be implanted with DBS electrodes, but only half of them will be turned on at first, and neither patients nor the doctors who study them will know which devices are active. After two years of double-blind study, all the electrodes will be turned on, then monitoring will continue.

The study will likely cost about $60 million. Charles said funding will hopefully come from DBS device manufacturers and Parkinson’s disease research groups, like the Michael J. Fox Foundation.

“Our study demands that we do this next trial,” Charles said. “We can’t have this signal on the table — that we may have a therapy that slows the progression of one of the cardinal features of the disease — and then let it lay at that.”

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For at least one Vanderbilt doctor, the study is looking for proof of what he already knows in his gut.

Dr. Peter Konrad, a neurosurgeon who has performed hundreds of DBS surgeries, said earlier this month he believes he has witnessed the electrodes slow the progression of Parkinson’s even if he wasn’t looking for it. After years of staying in contact with DBS patients, he noticed that many are far less debilitated than anyone would have expected.

“They should be in a nursing home by now, but they aren’t,” Konrad said. “We still don’t have the proof, but it is obvious to me they are in better shape.”

One of those patients was Dale Nevels, 68, a traveling salesman from Memphis, whose disease first surfaced in 2005 as a severe shoulder pain whenever he raised his arms or lifted his luggage. Doctors warned him then that Parkinson’s would slowly rob him of his ability to walk, speak and drive.

Two years later, Nevels volunteered for the Vanderbilt study. He still remembers the dulled sensation of medical instruments in his head, like the distant scraping of tree branches on a metal roof in a storm.

But, more than anything, he remembers the instant the electrode was turned on.

“My hands were … uncomplicated again,” Nevels said, pausing to find the words. “I was at peace.”

That was 11 years ago, and today Nevels is nearly the same man. Sometimes his speech slurs, but he can still talk. He leans on a cane as he walks, but he still walks. He can still write, type and drive. His Parkinson’s disease, which once threatened to rob him of his body, has been mostly held at bay.

“I’ve gone through the gauntlet and come out the other side and I am doing great,” Nevels said. “And I think a majority of the people who went through the program are doing great, too.”

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Brett Kelman is the health care reporter for The Tennessean. He can be reached at 615-259-8287 or at brett.kelman@tennessean.com.