Harry McGreevy is a 76-year-old retired machinist with Parkinson’s disease. It’s 6:44 on a March morning, and he is lying in the postanesthesia care unit at UPMC Presbyterian. The room buzzes with doctors, nurses, and other patients as McGreevy waits to begin a procedure to implant a stimulator in his head. The device will send electrical impulses deep into his brain, to the basal ganglia, which are gray matter nuclei associated with motor control, procedural learning, emotion, and routine behaviors (like eye movement).
McGreevy’s medication stopped working well several months ago, and he hopes this intervention, known as deep brain stimulation (DBS), will alleviate his Parkinson’s symptoms. He stumbles when he walks, has fallen four times in the past year, and this morning, his tremor blurs the U.S. Navy tattoo on his right forearm.
When R. Mark Richardson, an MD/PhD associate professor of neurological surgery, arrives at the foot of his bed, McGreevy expresses his eagerness to return to boxing class. Boxing can help Parkinson’s disease patients improve their balance and strength, but since McGreevy’s medication lost its effectiveness, he says he doesn’t have the coordination to work around his house, let alone punch a speed bag.
Richardson asks if McGreevy has any questions, and he shakes his head. “Nope,” he says. “Let’s get it done.”
Less than two hours later, McGreevy is in the operating room; his head is fitted into a stereotactic frame. He’s had a CT scan, which Richardson merges with a recent MRI, so he can pinpoint where in the basal ganglia to implant the electrodes. (It’s more complicated than this, but one goes on the right side and one on the left.)
This is the first of two surgeries. Today, Richardson’s team will implant the electrodes. In the next couple of weeks, during a second surgery, they will place a pulse generator in McGreevy’s chest and connect the electrodes by a wire running up the neck.
Along with the stereotactic frame, McGreevy has a smaller, box-shaped frame secured to his skull. Some of his white hair has been shaved off, and a wall of plastic over the stereotactic frame separates McGreevy’s body from his scalp and from the team. The surgeon cuts a semicircular incision on the right side of McGreevy’s head. Using a retractor, he spreads open the incision, and then he is handed a drill designed to make small cranial openings.
Richardson, who is director of both Pitt’s Brain Modulation Laboratory and the Movement Disorders and Epilepsy Surgery Program at UPMC, calls DBS the “gold standard” for treating cases of Parkinson’s disease like McGreevy’s, where there are treatment-resistant motor complications. DBS is not a cure, but it has a 70 percent success rate for easing symptoms in Parkinson’s disease patients. It’s even more effective for patients with essential tremor, working in 90 percent of cases.
For invasive brain surgery, the procedure is pretty safe for motor control patients. There’s a 1 percent chance of a stroke due to bleeding in the brain during the procedure and a 5 percent chance of infection.
Of course, an abundance of caution surrounds the procedure—not just among the surgeons who might recommend it.
Just reading about the surgery can be a deterrent. Vivian Scholze, a 67-year-old with essential tremor, received the procedure in September; but she first learned about DBS more than a decade ago. “I said, There’s no way I’d ever–” she recalls. “It’s extreme. I thought, Yeah right, and shave my head.”
Richardson has performed more than 300 DBS surgeries in seven years at Pitt. DBS is designed to be reversible. It’s more targeted than current interventions that bathe the brain and the rest of the body in chemicals.
Yet, he understands why there are hesitations about the procedure. He’s implanting foreign objects into a brain, placing a pacemaker-like battery into the chest, and connecting it all with a wire under the skin. Do we know enough about the brain to fiddle with it in this way? Can DBS somehow change who these patients are?
“The counterargument is,” Richardson says, “that we’re trying to restore these people’s identity.”
Scholze says she’s still amazed that she has a brain implant. Her life has become so normal—back to the way it was two decades ago—that she forgets she’s had the procedure. But then she bumps her chest, where the pulse generator slightly protrudes, and then she remembers how frail she once was.
“You’re not the same after,” she says. “You can see the difference in what you can do again.”
Patients undergo a neuropsychological evaluation before and after the procedure. The pre-DBS analysis is critical, because patients can be desperate or have unrealistic expectations. The evaluation also can identify whether cognitive symptoms of disease have progressed too far, in which case the team wouldn’t recommend surgery. The difficulties of mental decline, according to Richardson, can overwhelm a patient’s ability—and sometimes a patient’s family’s—to appreciate motor improvements. Psychiatrists suggest also screening Parkinson’s disease patients for problems with impulsiveness, since some have developed impulsive disorders after the procedure. (This can happen after taking Parkinson’s medications, too.)
The most profound DBS issue for Richardson: so few patients who qualify for the help actually get the procedure. Medical-device makers estimate that only 10 to 13 percent of eligible Parkinson’s patients receive the surgery.
On another winter day, Scholze demonstrates how effective DBS has been for her.
She is sitting at her dining room table at her home in Harrison City, Pa. A photograph of Scholze with her husband, Michael Scholze, together since they were 15, hangs on the wall.
Scholze clicks off her “brain pacemaker” with a remote control. Michael sets a glass of water in front of her on the table.
“Before the surgery, I had to hold my glass with two hands,” she says.
The pulse generator has been off just seconds, and there’s already a quiver in her voice. Before his wife had the DBS implant, Michael had to carry her plate through buffet lines. He cut her food and painted her toenails. She quit her office job because she couldn’t write, and one time, when she tried to make pancakes for her granddaughter, she flung batter all over the kitchen. She was diagnosed with essential tremor in the late 1990s, and by 2017, the amount of medication she took made her feel foggy and didn’t prevent the tremors. She felt embarrassed to leave the house.
“I literally didn’t have a life,” she says.
Scholze lifts up the glass, but she can’t even make it halfway to her mouth. Her arm trembles, splashing water on the table. She sets the glass down and turns the pulse generator back on.
After a few seconds, her arm tingles as the stimulator kicks in, and she picks up the glass.
“It’s gone,” she says of the tremor.
The quiver has left her voice, as well, and she sips the water without spilling a drop.
This switch-like effect is typical for DBS in essential tremor patients, according to Richardson. In the operating room, the immediate impact makes it easy to determine whether the electrode has been inserted into the correct place.
Scholze gets emotional recounting how Richardson’s team helped get her through the surgery. Scholze suffers from claustrophobia, and she felt unnerved waking up wearing the frame. Danielle Corson, Richardson’s physician assistant, held Scholze’s hand throughout the operation and testing.
“Thank God she was there,” Scholze says.
Once awake, essential tremor patients perform a drawing test, spiraling a pen in circles, and then signing their name. Scholze hadn’t signed her name in a decade before the procedure.
At her dining room table, Scholze’s eyes fill with tears at the memory of signing her name in the operating room.
Richardson is hopeful that DBS can give relief to others whose lives have been put on hold. He’s attempting to find ways to make DBS effective beyond offering patients renewed motor control.
Jordan Karp, associate professor of psychiatry, says “It’s an exciting time in clinical neuroscience here at Pitt.” That’s "in large part because of the clinical and research expertise that Mark Richardson and his functional surgery team have brought to our system. His work to advance the care and understanding of patients living with severe neurological diseases . . . really puts Pitt and UPMC in the vanguard.”
At the Medical College of Virginia, Richardson chose to study neurosurgery for DBS. He was drawn to the idea of improving a patient’s quality of life when medications stop working and there are no other options.
DBS also offers an extraordinary opportunity to learn more about the brain.
It used to be that doctors didn’t know why DBS was effective, but Richardson says that isn’t entirely true anymore. The basal ganglia are connected to the cerebral cortex by a series of loops that send signals through the thalamus to promote different kinds of behavior. There is a motor loop for modulating movements, a limbic loop for regulating emotions, and an associative loop for decision making. DBS disrupts pathological communication within a loop, while also allowing normal communication to occur.
Before DBS, some surgeons treated Parkinson’s and essential tremor with a lesioning surgery. Surgeons would place an electrode in the brain and apply a current to the area, giving the patient symptomatic relief. The pulse was increased until a permanent lesion formed. The lesion knocked out part of the circuit, allowing information to pass through the loop in a less pathological way.
In 1987, French neurosurgeon Alim Louis Benabid discovered that an electrode could be set to a lower charge and left on without causing permanent damage. A decade later, the Food and Drug Administration approved DBS in the United States as a treatment for essential tremor and tremors associated with Parkinson’s disease. The FDA approved DBS for advanced Parkinson’s disease symptoms in 2002.
DBS has also been attempted and studied for the alleviation of chronic pain and certain psychiatric conditions.
Two large, industry-sponsored trials of DBS for major depression were aborted by the sponsor when analyses showed that the primary endpoints would not be met. Richardson coauthored a paper with 35 other experts for the Journal of Neurology, Neurosurgery and Psychiatry that discussed concerns about the trials.
Richardson says the trials were begun prematurely by the device manufacturers, and in doing so, they muddied the waters for advancing DBS.
“Programs like [the National Institutes of Health’s] BRAIN Initiative are funding human neuroscience studies that we hope will provide a foundation for expanding the benefits of DBS,” he says.
Karp and Richardson have received FDA approval for a clinical trial of DBS for late-life, treatment-resistant depression, but they haven’t secured funding, yet.
And along with colleagues in the Department of Psychiatry—including Susanne Ahmari, Robert Hudak, and Lalith Solai—Richardson and Karp are expanding programs to treat patients with obsessive compulsive disorder (OCD).
In 2009, the FDA approved DBS to treat severe cases of OCD under the humanitarian device exemption. Richardson says the DBS success rate for OCD is unknown because no large-scale trials have been reported.
Despite the uncertainties, Randall Hirt, a 38-year-old West Mifflin, Pa., resident who was diagnosed with OCD in 2001, did not hesitate to get the procedure. Medication couldn’t help him control his morning routine obsessions. Habitually late, Hirt got fired from 17 jobs in four years, and his sense of self-purpose eroded to the point where he had a passive death wish.
But things changed following his 2016 surgery. “I was able to start getting places on time and early,” Hirt says. “I wasn’t impeded with different issues getting in my way. I could skip taking a shower or something like that.”
Hirt has become one of the most vocal patients in promoting DBS. He spoke at a neural ethics symposium held at Pitt last year and was featured on a KDKA News segment.
“One of the rewarding aspects of this comes from how much the patients want to participate in research and contribute to finding answers,” says Witold Lipski, a PhD and research instructor in the Department of Neurological Surgery.
Though his symptoms have improved, Hirt faces daily challenges because of OCD. He still takes medication and hasn’t been able to return to the workforce. His stimulation parameters probably need to be adjusted at his next doctor’s appointment. Tweaking a patient’s DBS during a regular checkup is common, even for a disease where the therapy is more effective, like Parkinson’s disease.
For example, in March, Dennis Troy, a 66-year-old Cranberry Township, Pa., resident, attends an appointment with Houman Homayoun, an MD and assistant professor of neurology, in the Kaufmann Medical Building in Oakland. Troy received a DBS implant last August for Parkinson’s and related conditions.
Homayoun begins the appointment by checking Troy’s rigidity. A retired computer programmer, Troy has read the neurostimulator’s clinical manual, and he has the checkup routine memorized.
As Homayoun asks him to perform a set of movements: Close your eyes. Now open. Give me your hands. With your right hand, open and close; now tap your fingers. And the left, open and close; now tap. Good. . . . Troy is a few seconds ahead of each command.
After observing Troy’s gait, Homayoun turns off the DBS, and they start the movements over. This time, Troy’s tremor is more noticeable, and he isn’t as fast. On his right side, Troy struggles with dystonia, a disorder in which muscle contractions result in unusual fixed postures; and in his feet, Troy has dyskinesia, an involuntary movement disorder similar to a tic or spasm. Troy guesses that, overall, his symptoms have improved 60 percent since having the surgery.
DBS for motor control benefits patients until they die, according to Richardson, but disease progression eventually outpaces the device’s ability to keep up with symptoms.
Using an iPad, Homayoun turns the DBS back on and increases Troy’s stimulation from 2.1 milliamps to 2.3 on his right side (to target his dystonia) and 2.1 to 2.2 on his left. He also adjusts the frequency and pulse width (the duration of the jolt) and gives Troy the ability to control the stimulation level on his remote. (Troy can’t turn it up higher than 2.5 milliamps.)
Homayoun rolls his chair around and shows Troy what he’s doing on the tablet. The screen displays a diagram of the tip of the electrode in his brain. The lead is 7.5 millimeters long, 1.27 millimeters in diameter, and it contains four contacts, which are each .5 millimeters apart. In the latest models, the two middle contacts are divided into thirds to help steer the current. Patients aren’t in control of which contacts are being used.
At the end of the appointment, Homayoun asks Troy if he would volunteer to speak to a group of Pitt Med students during a presentation. Troy and his wife, Linda, agree to be there. They didn’t hesitate to help. “I had a ton of the stupidest questions, and Dr. Richardson answered all of them,” Linda Troy says. “I love that man. He’s our hero.”
Richardson is leading a multidisciplinary team of experts from Pitt, Carnegie Mellon University, and Johns Hopkins University in a study exploring how Parkinson’s disease impacts speech. The research is supported by a $3.3 million grant, awarded over a three-year period, and is part of the BRAIN Initiative. DBS doesn’t usually help Parkinson’s disease patients with speech difficulties, and can sometimes make those difficulties worse. Richardson would like to change that.
Richardson’s study attempts to understand what activities in the subthalamic nucleus (STN)—which is part of the basal ganglia—are responsible for different aspects of speech (like articulation, pitch, efficiency, and volume). To do this, researchers record brain activity during DBS surgery as patients are asked to perform a variety of speech tasks.
Patients are placed under conscious sedation (also called twilight anesthesia). And yes, they are then woken up in the middle of brain surgery. As you may recall, patients have to be awake anyway for Richardson’s team to make sure the electrodes have been inserted in the right places (Although some patients may be eligible for a new “Asleep DBS” option at UPMC). Like most of Richardson’s patients, McGreevy is happy to volunteer.
“If it works for me, it’s going to work for someone else,” he says.
Corson, the physician assistant, stands next to McGreevy in the operating room. Holding his hand, she pats his arm and asks him to wake up for the speech production task. A hair-thin microelectrode has been implanted on the right side of his brain. Richardson’s team is recording brain waves from the cortical surface and from the lens shaped STN, as well as single neuron activity. Richardson hopes that these recordings will push his team closer to understanding speech production and how to design a DBS that can modulate speech separately from other motor activity.
While the speech task is going on, McGreevy’s brain also is being mapped by the same microelectrode to verify that the team has reached the target site to treat his Parkinson’s symptoms. The team listens in on his neuronal activity. They’ll know they are in the right spot when the neurons make a specific firing pattern. This typically takes about 30 minutes.
Meanwhile, Lipski adjusts a microphone in front of McGreevy. A video camera also is aimed at him. McGreevy says he’s ready to begin, and Corson asks him to repeat after her: “Today is a sunny day in Pittsburgh.”
“Today is a sunny day in Pittsburgh,” he says.
Richardson says he asks each of his patients to say this to assess baseline speech.
“I like this line because it often gets an interesting response,” Richardson says. “And my typical response for those who challenge its veracity, is that it’s a philosophy, not necessarily a weather report.”
Next, McGreevy repeats syllable strings that are told to him through headphones. “Vah, tee, shoo.” He’s asked to say some sets softly, others loudly, and then at a normal tone: “Ta, see, vee.”
At one point, the team had to move the electrode to a different location in McGreevy’s basal ganglia, and they are about to do the speech task again. Corson drapes a blanket across McGreevy to keep him warm and wets his mouth with a water-soaked sponge.
When Richardson asks if he’s okay to do more testing, McGreevy says yes without hesitating. He’s had a metal frame affixed to his head for several hours. There is a coin-sized opening in his skull, and he wants to help.
“Repeat after me,” Corson says, “today is a sunny day in Pittsburgh.”
“Is it?” McGreevy says, sarcastically. And the operating room erupts in laughter.
Richardson portrait courtesy ©UPMC Creative Services/Mark Bolster.
DBS device image courtesy Abbott.