Sixteen years ago, Ron Nickelson was jogging in the snow near his home in Cincinnati when he realized the leg cramp he’d been trying to power through wasn’t just a spasm. His left foot was turned in and the muscles were frozen; in fact, he’d been running on the outer edge of his shoe.
By the time he got back to his house that day, part of his left hand also had gone numb.
An initial misdiagnosis sent him down the wrong treatment path, and for two years the symptoms — including painfully stiff muscles, tremors and balance issues — continued. In 2004, he sought out a neurologist for a second opinion, and after a series of tests the new doctor concluded Nickelson was experiencing the early stages of Parkinson’s disease.
“The doctor saw my reaction and said, ‘You’re not surprised?’” said Nickelson, who was 48 at the time. “I told him I felt blessed. Of all the major neurological diseases I could have had — Parkinson’s, multiple sclerosis, muscular dystrophy, Huntington’s — Parkinson’s is the easiest to manage.”
That doesn’t mean living with an (as yet) incurable, degenerative disease that slowly destroys the part of the brain controlling your motor system is, by any means, easy. While most of the roughly 60,000 people diagnosed with Parkinson’s disease in the U.S. each year initially respond well to drug therapies, with prolonged use the drugs become less effective at controlling symptoms and, long term, cause side effects similar to those of the disease.
At that point, it can be too late even for the current go-to surgery, deep brain stimulation, which involves the implantation of microelectrodes in the brain.
“Surgery is not a cure, but it brings things to a halt. Part of the problem with these advanced treatments, though, is people wait too long to get them,” he said.
Parkinson’s robs the brain of a chemical called dopamine that facilitates the communication between cells. No one knows, for sure, why some people develop the disease, but studies have shown the interplay of biology and environment holds a critical role. Such theories ring true to Nickelson.
“Genetics loads the gun, and environment pulls the trigger,” said Nickelson, who can recall, as a child, frolicking in the fog clouds of passing pesticide trucks as they trawled his neighborhood. “We’d go running through it, throwing up our arms. We were just a bunch of dumb kids.”
In 2012, a movement specialist declared him an “ideal candidate” for deep brain stimulation, but the idea of brain surgery while awake — and the lengthy recovery and adjustment period afterward — was “intimidating,” he said.
Plus, he’d been keeping up with advancements in treatments on the website of the Michael J. Fox Foundation, the nonprofit set up by the former Hollywood star, who retired from acting two years after going public with his diagnosis in 1998. There, Nickelson read about a revolutionary new approach that was being applied to a growing family of ailments and was poised to enter the clinical trial phase of the U.S. Food and Drug Administration’s approval gauntlet as a treatment for Parkinson’s.
“When they told me I was a good candidate for DBS, I said, ‘I’ll wait for focused ultrasound,’” Nickelson said. “I guess I rolled the dice.”
The gamble paid off.
Soon after, Nickelson, a professional book editor, and his wife moved to Colorado Springs in the summer of 2016, he applied to participate in a clinical research trial that had just opened up at three U.S. hospitals, including Ohio State University’s Wexner Medical Center. Ultimately, Nickelson was among more than two dozen Parkinson’s patients chosen to undergo the experimental treatment, which used focused ultrasound waves to destroy the part of their brains responsible for the worst symptoms, without damaging surrounding tissue.
Focused ultrasound is performed while the patient is in an MRI chamber, wearing a transducer helmet that allows for precision direction of more than 1,000 high-intensity ultrasound waves, said Ohio neurosurgeon Dr. Vibhor Krishna.
Where those 1,000-plus beams meet, a lesion is created. In Nickelson’s case, that area of destruction measured 6x5x4 millimeters.
“By itself, a beam is not enough to do anything, but when 1,000 meet at a focal point it’s enough to raise the temperature enough to cause damage to cells,” said Krishna, who performed the technique on Nickelson in late December 2016.
The goal, as it is with deep brain stimulation, is to control — or in the case of focused ultrasound — destroy the part of the brain that’s “misfiring” and sending out distorted signals, “without opening the skull or drilling a hole in the skull,” Krishna said.
In deep brain stimulation, microelectrodes are implanted in these areas and the haywire signals controlled by a pacemakerlike device. Unlike deep brain stimulation, focused ultrasound is only done on one side of the brain, however.
Krishna said that patient outcomes are similar to those resulting from an older technique known as pallidotomy. That surgery also destroyed a minuscule region of brain tissue — in both hemispheres of the brain — but required opening the skull and was known to cause severe side effects to speech and balance.
With the noninvasive focused ultrasound, patients have seen from 40 percent to 50 percent improvement in symptoms, and no marked downsides, Krishna said.
Based on successful outcomes from the first clinical trial, the approval process has entered phase three of FDA testing.
“This is an initial study at several centers across the world,” said Krishna, of the technique that’s been approved in the U.S. for the treatment of essential tremor, uterine fibroids and bone metastases. “Typically, based on the results of such a study, the FDA makes a determination. ... I imagine, in the next three to five years, is what we’re looking at.”
Nickelson chose to have focused ultrasound on the right hemisphere of his brain, since his symptoms — including painful muscle cramps known as dystonia — were worse on the left side of his body.
“It was three-and-a-half hours in the MRI, and they kept pulling me out, every so often, to check my mental and motor skills,” said Nickelson, adding that he felt the effects almost immediately. “While I was in the tube, my dystonia behaved like it never had before, starting on the right side.”
His speech improved, too. That and other motor skills continued to improve over the following days. Two years later, Nickelson said his symptoms and the dosage of his medications have remained stable. He says he’s experienced no negative side effects and, what’s more, has managed to regain the 25 pounds the disease melted from his already slender 6-foot-4 inch frame.
“No question, focused ultrasound allowed me to keep living my life, keep working, exercising, doing what I’m doing,” he said.
While each patient’s experience with Parkinson’s and its treatments is unique, Nickelson said he feels like he “won the lottery.”
“I went to a Parkinson’s support group and sat down at a table with a guy who looked like he was in really bad shape, and he said ‘How long have you had it?’” said Nickelson, who told the man it had been 16 years. “He said, ‘How come you look so good? I’ve only had it one year.’”
Nickelson then told him about focused ultrasound.
“I really think it is the tipping point in medicine, and not just for Parkinson’s,” he said. “This really is a game changer.”