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Wired for Life: Device Short Circuits Seizures

— When nothing else works, this device may be best option in epilepsy

MedpageToday
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Froedtert Hospital neurosurgeon Wade Mueller (right) implanting a lead into Ryan Diettrich's brain. Mueller is assisted by two neurosurgery fellows. --- John Fauber photo

For some people whose epilepsy can't be controlled with medicine, surgically removing a small piece of the brain can reduce seizures.

Unfortunately, Ryan Diettrich isn't one of those people.

He needed another option and he found one. In October, Diettrich, 24, joined a small fraternity of epilepsy patients who are controlling seizures by shocking the brain into good order -- a technology that takes its cues from the ICDs, which prevent hearts from slipping into dangerous arrhythmias by supplying life-saving shocks.

There now are hundreds of such patients. There are likely to be many more.

The idea is one that has intrigued neuroscientists for decades: Sending electrical current into the brain in order to cure or at least manage various diseases, including epilepsy, major depression, multiple sclerosis, Parkinson's disease, and obsessive-compulsive disorder.

Seizures stem from abnormal electrical activity. Like fighting fire with fire, electrically stimulating the brain can disrupt that and return it to a more normal pattern.

First, a Trance

Diettrich, who grew up in Wisconsin, was an athletic kid. He played soccer and snowboarded -- and he played hard, suffering concussions in both sports. In the eighth grade he fell while snowboarding and was knocked unconscious.

It's not clear whether there's a specific connection between the concussions and his current challenges. Either way, Diettrich's seizures started when he was 15.

He was in his yard with friends getting ready to go a Milwaukee Brewers game. Suddenly, he seemed to go into a trance.

"I couldn't communicate," he said. "I started getting really bad sweats."

It lasted about a minute and a half. "It scared me a little, but I just brushed it off."

Less than a decade later, his condition had disrupted virtually every facet of Diettrich's life.

He could not drive or work.

He took five different anti-seizure medications a day, and even with that still was having two to four seizures a month.

He and friends from high school had drifted apart. Twenty-somethings often drink when they socialize and too much drinking was a sure-fire way to bring on a seizure.

A Chance for Normal Life

Returning to a more normal existence would depend on how his brain adapted to new hardware, specifically to the electrical changes that would quietly occur in the months and years to come.

Before Diettrich was wheeled into the Froedtert Hospital operating room the morning of Oct. 12, brain surgeon Wade Mueller, MD, told him and his family how the system would work.

The main goal during the operation would be to insert two, five-inch-long electrodes into predetermined areas on both sides of the brain where the abnormal electrical activity that causes his seizures emanated from.

Unlike other forms of brain stimulation, the RNS system, made by the company NeuroPace, doesn't just deliver continuous electrical current.

First, it looks for abnormal electrical activity. When abnormal activity occurs -- and it can happen dozens of times a day -- a neurostimulator implanted in the skull delivers electrical current designed to disrupt it.

"You're going to be a new man," said his mother, Sue Baker as he was headed for the operating room.

She didn't see him again for 6 hours.

Hitting the Targets

In the operating room, Diettrich lay face down covered in a tent of blue sterile sheets. Only a portion of the back of his head was visible.

After drilling portals into the back of his skull, the first electrode was inserted at 10:15 a.m. About 20 minutes later the second was implanted.

A mobile CT scanning unit was brought in the operating room to check whether the electrodes had reached their targets, which are small. Even being off a little could mean that part of the operation would have to be done again.

"We are hoping that never happens," said neurologist Christopher Anderson, MD, one of nearly a dozen people crowded into the operating room.

Technicians wearing lead-lined protective gear prepared to scan Diettrich's brain.

"All right, there is going to be radiation, so everybody needs to get out," Mueller said.

A few minutes later the results came in.

"The right one is right on the nose," Mueller says. "The left one is a tiny bit off, but it's right in the tissue we want so we are going to keep it."

The first part of the operation was done.

Dozens of Experiments

Searching clinicaltrials.gov using "deep brain stimulation" turns up more than 300 of entries involving a virtual compendium of things that can go wrong with the human brain. There have been experiments, many of them small, going on all over the world using brain stimulation to treat everything from anorexia to obesity to schizophrenia to Alzheimer's disease.

Since the 1950s doctors have experimented with sending electricity into the brain as way to treat various ailments.

Today, electrical brain implant devices are approved in the U.S. to treat Parkinson's disease; essential tremor, a movement disorder; dystonia, a disorder that involves involuntary muscle contractions; and obsessive compulsive disorder as well as seizures.

There are a few theories about why electrically stimulating the brain can improve symptoms of various diseases. It may beneficially inhibit or excite brain cell activity or even promote the release of brain chemicals known as neurotransmitters.

"The language of the brain is electricity," said Ali Rezai, MD, an Ohio State University neurosurgeon.

The trick, of course, is being able to deliver it to the right place at the right time in the right amount.

Rezai has been testing brain stimulation as a possible treatment for Alzheimer's disease, obesity, and in patients who have suffered traumatic brain injury.

Despite drugs and other treatments many patients who undergo brain stimulation have no other options, he said.

"We have to find ways to help these people," he said.

For the next 10 or 20 years, brain stimulation may be the best option for treating difficult diseases, said Konstantin Slavin, MD, a professor of neurosurgery at the University of Illinois College of Medicine at Chicago.

"But as time goes on, people will laugh at us for putting wires in people's brains," he said. "Right now we are treating symptoms. Eventually, treatments will be aimed at the cause and not the effect."

Improvement Over Time

The NeuroPace device, which was approved in 2013, is the first deep brain system for use in treating seizures.

It is an expensive technology with potentially serious risks such as infections and bleeding in the brain. It is only an option for those who have failed -- or are not candidates for -- other treatments.

Still, the company estimates that as many as 400,000 people in the U.S. could benefit from it.

Froedtert Hospital said the charges for Diettrich's surgery, including the device, were $146,000, though the actual amount paid depends on insurance. The insurance of Diettrich's stepfather, Tom Baker, provided his primary coverage for the surgery.

At a 2013 U.S. Food and Drug Administration advisory committee meeting, experts raised concerns about just how beneficial the device is and who was most likely to benefit.

But in a 3-month clinical trial of 191 people with intractable epilepsy, seizures were reduced 38%, compared with 17% in those who received the device but in whom stimulation was not turned on. While seizures were reduced, they were not eliminated in the vast majority of patients.

Further, some secondary measures of potential benefit did not show more improvement or reach statistical significance.

During the 3-month trial, 29% of patients who had the device turned on had a 50% or greater reduction in seizures, but so too did 27% of those in whom the device was not turned on. And there was no difference in the number of seizure-free days or the severity of seizures.

In a quality of life assessment, 37% of those who had the device turned on had a significant improvement, compared with 39% of those in whom the device was not turned on.

Part of that might due to a medical mystery known as the "surgical effect." For some reason, seizures can decline at least temporarily after brain surgery. Doctors don't know whether it is due to a type of placebo effect, an artifact of the surgery itself or simply regression to the mean.

Encouragingly, by the third month of the trial, the reduction in seizures improved to 42% versus 9% in those in whom the device was turned off.

After 3 months, the more rigorous part of the clinical trial ended and all of the patients were allowed to have the device turned on.

After a year, 44% of them had at least a 50% reduction in seizures. After 2 years that number grew to 55%.

"I think it is a nice tool," said neurologist and epilepsy specialist, Jeffrey Kennedy, MD, at the University of California Davis where three of the NeuroPace devices have been implanted.

While it is not a cure, most patients would welcome a 50% reduction in seizures, he said.

"The device seems to work better the longer it is in," added neurologist Anderson, of Froedtert Hospital and the Medical College of Wisconsin.

Patients admitted into the study were the most difficult patients to treat, said NeuroPace CEO Frank Fischer.

They came into the trial taking about three drugs a day and still had uncontrolled seizures for an average of 20 years.

One-third of them had failed surgery for their seizures and another third failed to benefit from an older device known as the vagus nerve stimulator, which sends electrical current into the brain via a nerve in the neck, he said.

Wired and Ready

The smell of bone being cut away by a drill wafted through the room as doctors removed a portion of the back of Diettrich's skull that would house the RNS neurostimulator. It was 2.4 inches long, 1.1 inches wide and 0.3 inches thick.

The titanium device, which included a battery and a programmable computer chip, rested in a contoured tray screwed into the opening in Diettrich's skull.

Two leads came out of the stimulator. Their job: to send current to electrodes deep in his brain.

Diettrich's brain wave activity was monitored as doctors did a final test to make sure the electrodes were in the target area.

"You hit it," said neurologist Anderson, looking at a monitor.

"That's what I want to hear," said surgeon, Mueller.

At 11:45 a.m. Diettrich's scalp was pulled back into place and sewed up.

A few minutes later, Mueller met with Diettrich's family in a waiting room.

"What's it going to be like when he wakes up?" his mother asked.

He will have bad headaches for a couple days, Mueller said.

She also asked whether her son's memory will improve.

"I have no idea," he said.

Looking Ahead

On Oct. 24, 12 days after being implanted with the device, Diettrich had a seizure. Since the device was not yet turned on, it was not unexpected.

The next day he met with neurologist Anderson at Froedtert.

Christopher Anderson, MD, a Froedtert Hospital neurologist, changes the settings on Ryan Diettrich's RNS neurostimulator. -- Milwaukee Journal Sentinel photo by Rick Wood

"I'd say the majority of it came in my sleep," Diettrich said. "I was just really out of it."

Anderson went to a website operated by NeuroPace where he downloaded data that Diettrich had sent to the site from home by using a laptop and a magnetic wand that he runs over his head. Hundreds of patients with the device also are doing that, creating a huge database of brainwave activity that can be used to figure out the best way to program the devices.

It appeared the seizure lasted about a minute, and occurred on the left side of the brain.

Anderson then programmed the neurostimulator to respond when the next seizure occurs.

He used very low settings, probably one-tenth of what ultimately will be needed.

"Let's see how you do," he said. "If you have another seizure, just call."

Less than 3 weeks later, a second seizure occurred. It was a big one, and the device did not stop it.

It took Diettrich 3 days to recover.

It left him worried about how many more seizures he would endure before the device would begin working the way he had hoped.

Diettrich wants to be able to drive again and start working. In Wisconsin, that means being seizure-free for at least 3 months before getting behind the wheel.

"A lot of my focus is on working," he said. "I've got student loans and bills to pay. It's been an up and down road. I am just focused on the future, not the present."

"My mood has picked up a lot," he said.

He has not had any seizures that he has been aware of since Nov. 12, but according to data downloaded from the device he had a seizure on Dec. 21. He was unaware of it.

In early January, Diettrich began helping his older brother, who runs an electrical company in Florida.

The man with wiring in his brain, now is wiring new homes.