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Doctors Are Zapping Parkinson’s with Pacemakers for the Brain

At Stanford and UCSF, researchers are finding ways to tailor treatment to individual patients' brains.

 

In 1958, a 43-year-old cardiac arrhythmia patient named Arne Larsson received the first implantable pacemaker. It was rudimentary and lasted only a few hours, but with the help of 25 more such devices, Larsson lived another 43 years. Today’s cardiac pacemakers are tiny, about the size of a half dollar, and can last for 10 years. 

Now, decades later, doctors including Stanford neurologist Helen Bronte-Stewart and UCSF’s Phillip Starr are testing early technology for a similarly small, rechargeable pacemaker for the brain that could help patients with Parkinson’s disease—and potentially even depression and obsessive-compulsive disorder—possibly within the next decade. “I am quite a cautious person in making these kinds of projections, but the technology is moving forward quickly,” says Bronte-Stewart, who runs an eponymous movement-disorders lab at Stanford. “I think we will see the therapy change a lot in the next 5 to 10 years.” 

Brain pacemakers already exist: Parkinson’s patients use them for a therapy called deep brain stimulation, which can alleviate symptoms like tremors and muscle rigidity. DBS—the application of electrical stimulation to deep brain structures—was approved by the FDA to treat Parkinson’s symptoms in 2002, but scientists still aren’t entirely sure how it works. The current thought is that much like the heart, the brain has rhythms that affect its function, and sometimes those rhythms are off. It’s possible that DBS overrides those abnormal rhythms, allowing the brain to coordinate sensory and motor information. “It’s like trying to listen to the radio, and the station is off,” Bronte-Stewart says. “You can only sort of hear what’s being said. DBS helps you hear that station again.” 

For patients like Kevin Kwok, 54, who has been working with Bronte-Stewart in clinical trials, DBS has been life changing. Kwok, who was diagnosed with Parkinson’s in his late 40s, suffered from muscle rigidity that caused the left side of his body to sag. After starting DBS in the lab with Bronte-Stewart, he was able to go off his medications entirely. “It’s like you set the clock back eight years,” he says. “When you turn DBS off, my left side looks like a stroke victim.”

But DBS isn’t perfect. Doctors can adjust voltage, pulse width, and frequency based on what they think each patient needs, but there hasn’t really been a way to measure brain waves to know for sure. And overtreatment may have side effects. “You can see how primitive we are with the therapy now,” Bronte-Stewart says. “It’s one size fits all.” 

But a handful of labs around the world are working to change that. In 2013, a medical device company called Medtronic gave two U.S. hospitals, Stanford and UCSF, the opportunity to test a device capable of measuring brain waves in real time—something previously possible only during surgery.

The hope was that the device, called Activa PC + S, would eventually allow Bronte-Stewart’s team to use the brain-rhythm recordings to determine the right dose of DBS for each patient. If that were possible, the team could also potentially figure out a way to automate the process, so that a combination of devices could determine and deliver the correct dose without help from a doctor. At Stanford, Kwok and 19 other volunteers had metal leads implanted in the motor regions of their deep brain structures. The leads were attached to wires that ran out of the top of their skull, under their skin, and down to a sensing neuro-stimulator device implanted in their chest.

In one trial, the volunteer patients wore smart-watch sensors on their wrist to measure their tremors. When the accelero­meters and gyroscopes in the smart watch sent motor feedback via Bluetooth to a specifically programmed PC, the PC—with no human intervention—determined exactly how much DBS was needed and communicated that to the Medtronic device implanted in each patient’s chest, which delivered the correct dose via the leads implanted in their brain. Though the team supervised the research, the process took care of itself. Bronte-Stewart and her colleagues could actually see patient tremors resolve as the DBS was delivered. “It worked,” Bronte-Stewart says. “It was absolutely fascinating to see. Everyone’s tremor responded. I was blinded.” Six months into the research, Bronte-Stewart and her colleagues found that some patients needed DBS only about 15 percent of the time—and that none needed it 100 percent of the time.

“I’ve been an electrophysiologist for many years, and even for me it was surprising,” says Adria Martig, associate director of research programs at the Michael J. Fox Foundation for Parkinson’s Research, which has funded some of Bronte-Stewart’s research with the Medtronic device. “Seeing this getting so close to the clinic was so exciting for me. It really is that groundbreaking.”


Originally published in the January issue of
San Francisco

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