Journey to the center of the brain
Since 2002, UF Health physicians Michael S. Okun, M.D., and Kelly D. Foote, M.D., have been using a technique called deep brain stimulation to treat patients stricken with movement-limiting conditions. This is the story of one of these patients, and how Okun, Foote and their team are correcting the brain’s circuitry through surgery … and a little electricity.
By Morgan Sherburne
Inside your brain, neurons fire and send messages to different parts of your body. One region of the brain, the globus pallidus, helps govern voluntary movements. It helps tell your hands to lift smoothly, write neatly, play the saxophone. When the cells fire, they give off specific sounds. Cells of the globus pallidus may sound like they are humming or singing, says Michael S. Okun, M.D., co-director of the UF Health Center for Movement Disorders and Neurorestoration. Cells on the border of the internal and external part of the globus pallidus have a low, consistent tonic hum like the ticking of a motorboat. The soft, whooshing sounds that Okun hears while he’s listening to a person’s brain? Those are optic tract cells that are important to vision.
“If you’re mapping the globus pallidus of someone with dystonia, you are looking for really tonic, bursting, noisy cells that are angry and firing like crazy,” Okun says.
When Okun is listening to the brain, he is listening for something that sounds wrong in the region of the globus pallidus. In the brain of 14-year-old Felipe Hanel, the globus pallidus should fire in regular tones. Instead, Felipe’s globus pallidus — a tiny structure just 3 millimeters across — fires in “regularly irregular packets,” what Okun terms a “cacophony.” The sound is a signature pattern for a neurological disorder.
The sound of the structure indicates Felipe’s disorder. Felipe has dystonia. Dystonia is a neurologic movement disorder, which causes his hands to curl, his legs to contort, and affects the way he walks. But neurologist Okun and partner neurosurgeon Kelly D. Foote, M.D., also a co-director of the center, are refining a procedure called deep brain stimulation to ease Felipe’s symptoms.
Felipe was diagnosed with dystonia in 2011. The Jacksonville ninth-grader began developing symptoms in 2009, when he was in third grade. Martina Kranich, Felipe’s mother, noticed Felipe’s handwriting, normally neat, had started to become sloppy. He suddenly held his juice cup with both hands. After a day at Disney, he started to walk on the outside of his foot.
Martina told him how to walk: heel first. Felipe tried, she says, but he couldn’t force his foot in the correct posture. His knee hurt.
His family suspected he had essential tremor, which his paternal grandfather has. But further testing turned up the diagnosis of dystonia. Dystonia is similar to, but more complex than a tremor disorder, Foote says. Tremor disorders commonly affect the communication between the thalamus, the cortex and the cerebellum in the brain. The job of this circuit is to modulate movement to make sure you’re moving smoothly and are able to function in everyday activities.
In patients with tremor, that circuit gets interrupted.
“There’s a population of neurons that are supposed to be helping you move better, but instead, they’re just firing at the frequency of your tremor,” Foote says.
In each dystonia patient, the brain’s circuitry becomes scrambled.
“What happens in dystonia is the commands from the brain to the muscles become disorganized,” Foote says.
For example, if you want to curl your bicep, your brain must tell your arm to relax your tricep at the same time. In dystonia, the brain may get mixed up and command your body to contract separate muscles at the same time, causing a person’s limbs to become twisted.
A family friend, also a brain surgeon, recommended Foote and Okun to Felipe’s worried parents.
Lucky number 1,000
During the deep brain stimulation surgery, Felipe is awake, as are most deep brain stimulation patients. Foote implants a tiny wire electrode called a DBS lead into Felipe’s brain — the 1,000th such lead Foote and Okun have implanted since they began performing the procedure at UF in 2002. He’s awake because Foote and Okun map the brain and later test whether they have placed the lead in the correct spot.
“I know the place I ultimately want to stimulate in order to help someone with dystonia,” Foote says. “With the patient awake, Mike can map it for me and then we can test out a lead and, for example, be sure we don’t tickle the optic track and make them see spots.”
The doctors also can tell whether the stimulation is causing a patient’s face to pull, triggering strange prickling sensations, or causing slurred speech.
Felipe takes the surgery in with a young teenager’s curiosity. When he gets nervous, he thinks about his dad.
“I was trying not to focus much about what was going on in my head,” Felipe says. “I kept thinking about my dad. This is the kind of stuff my dad sees every day. He’s a brain surgeon, and that helped my confidence level for the surgery itself.”
First, Foote secures Felipe’s head in a halo. He makes an incision in Felipe’s scalp after carefully numbing it — he doesn’t even have to shave Felipe’s hair. Felipe feels a little pressure as Foote drills a dime-sized hole in his skull, then a small ache as Foote cuts through the dura mater, the tough, leathery casing that protects his brain. Once inside, Felipe won’t feel the placement of the lead: the inside of the brain has no nerve endings. This is the one of the reasons the patient can remain awake and participate in the surgery.
The lead has four contacts and is connected to an extension cable, which runs under Felipe’s skin and down to his chest. During a follow-up surgery in late May, Foote implanted a device called an impulse generator, or neurostimulator, in the 14-year-old’s chest. That generator delivers pulses of electricity that modulate the problematic pulses of the neurons causing Felipe’s symptoms.
Martina, Felipe’s mother, said they have already
seen some improvements. Specifically, Felipe’s left arm, the limb most affected over the past year, is moving more easily.
“We are so happy for him; his friends are happy for him; he is happy,” Martina says.
Two days after his second surgery, Felipe attended his eighth-grade dance.
The beginning of the partnership
Foote, a neurosurgeon, and Okun, a neurologist, have been working together since 2002. The doctors have been advancing deep brain stimulation at the UF Health Center for Movement Disorders and Neurorestoration since founding the center.
“Kelly Foote and Mike Okun have established one of the world’s best deep brain stimulation programs at the University of Florida,” said William Friedman, M.D., chair of the department of neurosurgery in the UF College of Medicine. “They are internationally renowned for their contributions to this field.”
About 100,000 patients have been implanted with deep brain stimulators since 1997, when DBS was first approved for the treatment of tremor. Foote and Okun account for 1,000 of the leads associated with these surgeries. The team implants about 150 leads a year, and the center has more patients annually than any other DBS clinic in Florida.
The two are prolific because Foote’s clinical practice largely focuses on deep brain stimulation surgeries. This focus has allowed the researchers to hone their abilities in the operating room.
“Back in those early days, we could not see what we were aiming at in the OR. We had a good idea based on landmarks, but there wasn’t very good imaging resolution on the structures of the brain,” Okun says.
The two planned the deep brain stimulation surgeries on the basis of a 3-D image drawn from MRI and CT scans — and listening to the music of the brain. Now, Foote plans the surgery in a similar way, but the images of the brain are much sharper. With help from Frank Bova, Ph.D., a professor of neurosurgery, they designed a computer software package to plan the surgery, inputting the image of the patient’s brain and the location of the problematic area. First, Foote performs the operation virtually, on the computer program. Then, he performs the surgery on the actual patient by setting the coordinates into the head frame attachment. The head frame attachment hooks to the halo stabilizing the patient’s skull, and guides the lead to the target within the brain.
Meanwhile, Okun uses the lead to convert the nerve signals out of the brain then digitize those signals into sound.
“That way, you have both a visual representation and auditory representation of how the neurons are firing,” Okun says.
While he listens to the brain sing, Okun follows his progress on the computer, finding the target site by both listening to the noises of the brain and mapping the brain’s structures.
“When you know you’re getting close to the target, you move slowly, one brain cell at a time,” Okun said. “If you’re not hearing something, there’s a lot of reasons that might be, and that may tell you that you are entering silent structures of the brain. In this game hearing nothing is something. Conversely, if there are changes in the ambient background — just like in a sporting event when the crowd begins to crescendo — you use these changes to define where you think structures are in the brain.”
The surgeries the two doctors perform are the result of more than a decade of partnership. Okun says the two have worked with many of the same team of doctors, engineers, nurses and technicians for a long time.
“Even in cases when the mapping becomes difficult, the team has been together so long, there’s no panic, no yelling, no losing of cool. It’s just a bunch of cool cats,” Okun says.
After the device is implanted, patients might not see results for months — for years prior, their brains have been sending conflicting commands, which can become hardwired into their bodies. It takes time for the brain to reorganize, Foote says.
“I’ve had patients with dystonia who have gone for three months with no apparent benefit, feeling that the surgery was a waste of time. Then, during the seventh month, all of a sudden the body starts responding and by nine months, the patient is virtually normal,” Foote says. “It’s extraordinarily gratifying.”
In May, Felipe had the impulse generator connected to the lead in his brain. Eventually, his hands should be able to take notes again in school. He will likely be able to walk normally. He should be able to pick his saxophone back up and play.
While the surgery might have satisfied a 14-year-old’s curiosity, Felipe thinks about his disorder with a level of poise that surpasses his age.
“There have definitely been times where I sort of think ‘Why me? This kind of sucks,’” Felipe says. “But then I just look at the kids at my school with special needs, and I see that in my case, there’s not much for me to be complaining about. That’s sort of my take on it.”