For decades, Keith Krehbiel took high doses of medications with a debilitating side effect—severe nausea—following his diagnosis with early-onset Parkinson’s disease at age 42 in 1997. When each dose wore off, he experienced dyskinesia—involuntary, repetitive muscle movements. In his case, this consisted of head bobbing and weaving. Krehbiel is among one million Americans who live with this progressive neurological disorder, which causes slowed movements, tremors and balance problems.
But soon after surgery to implant electrodes into specific areas of his brain in 2020, his life dramatically improved. “My tremor went away almost entirely,” says Krehbiel, now age 70 and a professor emeritus of political science at the Stanford Graduate School of Business, whose Parkinson’s symptoms began at age 40 and were initially misdiagnosed as repetitive stress injury from computer use. “I reduced my Parkinson’s meds by more than two thirds,” he adds. “And I no longer have a sensation of a foggy brain, nor nausea or dyskinesia.”
Krehbiel was the first participant to enroll in a clinical trial testing a new form of deep-brain stimulation (DBS), a technology that gained approval from the U.S. Food and Drug Administration for Parkinson’s tremor and essential tremor in 1997 (it was later approved for other symptoms and conditions). The new adaptive system adjusts stimulation levels automatically based on the person’s individual brain signals. In late February it received FDA approval for Parkinson’s disease ‘based on results of the international multicenter trial, which involved participants at 10 sites across a total of four countries—the U.S., the Netherlands, Canada and France.
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This technology is suitable for anyone with Parkinson’s, not just individuals in clinical trials, says Helen Bronte-Stewart, the recent trial’s global lead investigator and a neurologist specializing in movement disorders at Stanford Medicine. “Like a cardiac pacemaker that responds to the rhythms of the heart, adaptive deep-brain stimulation uses a person’s individual brain signals to control the electric pulses it delivers,” Bronte-Stewart says. “This makes it more personalized, precise and efficient than older DBS methods.”
“Traditional DBS delivers constant stimulation, which doesn’t always match the fluctuating symptoms of Parkinson’s disease,” adds neurologist Todd Herrington, another of the trial’s investigators and director of the deep-brain stimulation program at Massachusetts General Hospital. With adaptive DBS, “the goal is to adjust stimulation in real time to provide more effective symptom control, fewer side effects and improved patient quality of life.”
Current FDA approval of this adaptive system is for the treatment of Parkinson’s only, not essential tremor, dystonia (a neurological disorder that causes excessive, repetitive and involuntary muscle contractions) or epilepsy, which still rely on traditional, continuous DBS, Herrington says.
“Our personalized treatment can control debilitating tremors for a person living with Parkinson’s,” says Ashwini Sharan, chief medical officer of the neuromodulation operating unit at Medtronic, the Minneapolis-based medical device company that manufactures this technology. Placed under the skin of the chest, a DBS device transports electrical signals through very thin wires to an area in the brain that controls movement.
“Neuroscientists have been on a decades-long journey to decode brain signals to personalize the deep-brain stimulation experience,” says Michael S. Okun, national medical advisor to the Parkinson’s Foundation, who was not involved in the study. “The era of smart stimulation for Parkinson’s disease has arrived,” he adds, while cautioning that time will tell how well adaptive devices work, particularly for more challenging and frequently fluctuating symptoms.
Many people will not require adaptive stimulation to fully optimize control of Parkinson’s symptoms, but the new technology can make a big impact in select cases, says Okun, who is also executive director of the Norman Fixel Institute for Neurological Diseases at University of Florida Health.
“Although this is a significant advancement, it is still too early to determine whether its efficacy is superior to that of existing DBS systems,” adds Vibhash Sharma, a neurologist and medical director of UT Southwestern Medical Center’s neuromodulation movement disorders clinic. “More studies and data are needed to assess its effectiveness across a broader range of patients,” says Sharma, who was not involved in the new research.
The surgical technique for implanting a DBS device carries similar risks for conventional and adaptive systems. There’s a low risk of stroke, infection, hemorrhage and seizures during the placement of electrodes, Sharma says.
People with such implants may also experience stimulation-induced side effects—such as tingling, tightness or speech changes—if the electrical current spreads to surrounding areas of the brain. Adjustments may be required to avoid these effects.
John Lipp, another trial participant, said his use of the new system reduced the number of medications he takes for Parkinson’s from 15 to four. The 59-year-old chief executive officer of a nonprofit animal shelter in Alameda, Calif., received the diagnosis in June 2015, a month shy of his 50th birthday. His main symptom was dystonia, which he describes as “really intense muscle spasms and cramping.”
The dystonia almost disappeared after the device was implanted and turned on. When researchers initially made adjustments to the adaptive DBS settings as part of the study, he could feel his symptoms returning, but they subsided when the team made additional modifications.
Adaptive DBS isn’t a cure, Lipp says. “There are a variety of nonmotor symptoms, including sleep disruption, that I’m coping with on a daily basis,” he notes, adding that his neurologist monitors and adjusts the stimulation in keeping pace with the disease’s progression.
Recognizing that exercise helps slow down progression, Lipp wanted “to be as proactive as possible.” He ran his first marathon in 2016. “In the course of training, I lost weight, got stronger, and, ironically, got in the best shape of my life,” he says.
Lipp finished several marathons and half-marathons before his Parkinson’s symptoms got in the way. Last November, thanks to improvement he attributes to this new technology, he crossed the New York City Marathon’s finish line for a second time. He plans to run the same marathon this year.
