Taming Tremors

July 7, 2015
An elderly male patient with Parkinson’s disease grasps a walker.

The probe had reached its target deep in the brain of a woman torn by the ravages of Parkinson’s disease. Neurologist Jerrold Vitek, who had helped the surgeon guide the probe—actually an electrical lead—into place, asked the patient to draw a spiral. 

Her hand shook so violently, the drawing could barely be recognized—until Vitek switched on the current. Suddenly, her tremors subsided and the spiral took shape.

“Now can you write your name?” Vitek asked.

She began to write, but quickly stopped and began to smile and weep at the same time. Once an artist who had painted beautiful pictures, she came to surgery unable to write her name or even draw a simple spiral.

“I can now paint again,” she told the surgical team. “I haven’t been able to paint in years, since the tremors became so severe.” 

Stories like this have played out countless times in the five years since Vitek came to the University of Minnesota to lead the program in deep brain stimulation (DBS). In DBS, implanted electrodes electrically stimulate brain circuits to correct tremor or other disorders of movement associated with patients who have Parkinson’s disease, essential tremor, or dystonia.

As head of the Department of Neurology and director of the Neuromodulation Research Program, Vitek has built a nucleus of top-notch researchers and practitioners dedicated to making the U of M a world center for the myriad clinical, engineering, and imaging aspects of DBS. Judging by the U’s record of treating movement disorders, especially Parkinson’s disease, he is succeeding.

“The vast majority of Parkinson’s disease patients see marked improvement in their motor control, and now it’s being used to treat dystonia [debilitating involuntary muscle contractions] and obsessive-compulsive disorder,” says Vitek.  

“We want to lead the way in new technology, provide the best clinical outcomes, and treat conditions like addiction and depression, as well as other movement disorders. We could have an effect on any disorder related to brain circuitry by finding the affected circuit, characterizing what’s wrong with it, and determining where in the brain it is best to intervene.”

Diverse team, singular success

The U of M has taken its place among the continent’s top DBS providers, rivaling older programs at Emory University—started by Vitek—and Toronto Western Hospital, among others. If one thing sets the U’s program apart, it is the precision with which the leads are placed. Much of the credit for this belongs to Vitek, his colleague Ken Baker, and imaging expert Noam Harel

The electrodes—contact points—within a lead must reach a target area smaller than a pea. Moreover, its location within the skull varies enough that each patient’s brain must be mapped, using tiny devices called microelectrodes. Harel, an associate professor at the U’s Center for Magnetic Resonance Research (CMRR), uses images generated by the center’s 7 Tesla magnetic fields, along with CT scans, to construct detailed 3-D maps with sub-millimeter resolution. 

Harel’s group developed a way to capture images with the necessary information to make the map and also programmed computers to turn the images into 3-D models. For Parkinson’s patients, the lead is placed within the subthalamic nucleus (STN), or the internal segment of the globus pallidus (GPi), areas with dense clusters of neurons deep in the brain. Both house areas concerned with emotions, thinking, and motor control.

“We want to hit that particular part—the motor control area of the STN or GPi, not the other parts,” Harel says. “It’s location, location, location.

“No other [treatment center] does patient-specific anatomical models. Also, high-field MRI was largely developed here. [These are] sterling examples of applications.”

In the operating room, Vitek puts his special skills to work. As the neurosurgeon inserts the microelectrode, it picks up electrical signals from individual neurons. These are translated to characteristic sounds each type of brain tissue makes. 

“For example, border areas around nuclei like the GPi purr with a distinct motorboat sound, and silence implies no cells are nearby, so the probe is going from one area to another,” Vitek says.

He recognizes those sounds because he has mapped them, like mapping Europe by where the different languages are spoken. During surgeries he listens to the neuronal talk and guides neurosurgeons as they navigate to the optimal location in the target. Once the mapping is completed and the location to place the DBS lead determined, the lead is placed in the target. If the DBS probe ends up even a millimeter off-target, it can cause severe side effects. But at the U, that risk is small and shrinking.

“We’re more consistently accurate in placing leads, and we’re getting quicker,” says Vitek. And no wonder; Harel notes that “Jerry is the best mapper in the business. He did all the groundbreaking studies [behind mapping by listening to neurons during surgery]. His is a huge name in DBS.”

The brain itself cannot feel pain, so the patient stays awake and demonstrates how, for example, their tremors change in intensity as the lead closes in on its target.

Once in place, the lead is connected through a wire running beneath the skin to a neuromodulator unit implanted in the chest. It is programmed to deliver the right amount of current in the right rhythm to one or more electrical contacts on the lead, giving optimal stimulation.

That the operation and the patient’s recovery are so often successful testifies to the wide scope of care at the U.

“It takes a lot of planning and work to coordinate neurology, neurosurgery, physical medicine and rehabilitation, neuroradiology, basic sciences, and the CMRR,” notes neurosurgeon Michael Park, who was recruited to the University as part of the MnDRIVE initiative. “I think patients reap indirect benefits from all of them.”

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Leading research 

While the leads currently in use have an enviable success rate, researchers like Matt Johnson, an assistant professor in biomedical engineering, are improving their design by making them more tunable. 

Currently, leads are thin, hollow cylinders. The contact points—which deliver the current—are cylinders within the cylinder, arranged in tandem. Programmers can activate any or all of them to tailor the delivery of current to precise areas of the brain. But each contact generates current in 360 degrees. Such diffuse stimulation can cause side effects like muscle contraction or a tingling sensation.

“Now we’re developing probes where the contacts are elliptical and arranged in a ring around the circumference of the lead,” says Johnson. That, he explains, will allow finer control of where the current is delivered. “Data from these new leads will likely lead to clinical trials in the next few years,” he says.

Johnson and his students work closely with the Big Three of Minnesota’s medical device community: Medtronic, St. Jude, and Boston Scientific, along with a subsidiary of Greatbatch Medical of Plymouth, Minnesota. 

“Four of my Ph.D. students have had the opportunity of working at Medtronic during their graduate studies,” Johnson notes. “I think opportunities like these attract great students to the University of Minnesota.”

In the process, he adds, “we’re training Minnesota’s industrial work force.”

Getting the word out

Because DBS can be reprogrammed as a disease progresses, and unlike drugs carries no permanent risk of overdose, it is gaining ground as the treatment of choice. But of all the Parkinson’s patients in Minnesota who could potentially benefit from DBS, only about one in five gets it—“probably because they don’t know about it, not for medical reasons,” Vitek says.

For people living outside the metro area, Vitek—a born Iron Ranger—envisions a training program to teach health professionals, such as nurse practitioners, to program neuromodulators. This would spare patients the long trips to the Twin Cities for programming adjustments. Teleprogramming, already done for cardiac pacemakers, is another possibility, he says.

Support for DBS work also includes a MnDRIVE grant from the Legislature. The grant funded a Parkinson’s disease registry for research, led by Timothy Church, a professor of environmental health sciences. With fellowships for graduate students, postdocs, and doctors interested in advanced training in neuromodulation, the U is poised to expand its DBS program throughout Minnesota and beyond.

Harel recalls one patient for whom his team performed a pre-surgical scan:

“He was 46, with early-stage Parkinson’s disease. He couldn’t work, and he couldn’t do anything with his kids.” But after surgery, “he got his life back. Now he could spend time with his kids.”

And that’s what it’s all about.  

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