John Whitehead was in his 30s when his hands began shaking uncontrollably. At the time, he was working in the office of a fire department. "They had me drawing maps," recalls Whitehead, now 76. "I couldn’t get a straight line going."
He would later learn he had essential tremor (ET), a neurological condition that causes involuntary, rhythmic shaking during movement, most commonly affecting the hands. (Essential tremor is not related to Parkinson's disease, another condition marked by tremors.) Approximately 10 million Americans have ET. It can develop at any age but most often appears when people are between 40 and 50 years old. The condition typically worsens over time and can be aggravated by fatigue, stress, caffeine or extreme temperatures.
The exact cause of ET is unknown, but a number of inherited genetic mutations have been associated with the condition. Indeed, ET ran in Whitehead's family.
Over the years, Whitehead's tremor intensified to the point where he could no longer write his name or drink from a cup without spilling. "I started carrying a tablespoon to go out and eat. A regular spoon was too small and food would shake out. That got to be really aggravating."
He tried medications, but they were ineffective and caused unwanted side effects, and his condition continued to worsen. Then he heard about a treatment at UCSF that can help patients like him.
High-intensity focused ultrasound – "HIFU" for short – is an incisionless surgical procedure in which concentrated sound waves are used to target cells in a tiny area deep in the brain that is involved in generating tremors. The treatment doesn't cure ET but can significantly reduce tremors. Whitehead asked his doctor near his home in Elk Grove, California, to refer him.
"I ended up calling UCSF and hit the jackpot," he says. "It's been a life-changing experience."
Whitehead was referred to the UCSF Movement Disorders Clinic and Dr. Doris Wang, a neurosurgeon who specializes in caring for patients with movement disorders, including ET.
ET's first-line treatment is medications (including some used to treat high blood pressure and certain antiseizure meds), but up to 50% of ET patients don't respond to the drugs. When medications fail, surgical options such as deep brain stimulation (DBS), which involves implanting a device that sends electrical impulses to the brain to interrupt tremors, or ablative surgeries, which destroy brain tissues through heat or radiation, are highly effective.
HIFU is a new type of ablative surgery and has many advantages over DBS surgery, Wang says. There's no need to make an incision, and it doesn't require putting an implant in the body that later needs to be adjusted and replaced. "It has higher precision and higher safety than traditional ablative surgery techniques," Wang says. She now uses it for patients with ET who are either not good candidates for treatment with DBS or who do not wish to have brain implants.
In preparation for performing the treatment, Wang and Dr. Leo Sugrue, a neuroradiologist, use MRI to determine which specific areas of the patient's brain they will target and which areas they should avoid. The imaging allows them to personalize HIFU to each patient's brain anatomy, says Sugrue, a neuroradiologist and director of the UCSF Laboratory for Precision Neuroimaging. "On the day of the procedure, we have access to all the planning we have done."
During the procedure, high-intensity sound waves, guided by MRI, are focused on a tiny area in the brain called the ventral intermediate nucleus of the thalamus and dentatorubrothalamic tract. The waves pass through skin, skull and brain to safely destroy cells in the targeted area while leaving surrounding brain tissue unharmed. Patients are conscious the whole time. Improvements in the tremor are immediate, and patients go home an hour after the procedure.
"From the perspective of the treatment team, it's incredibly rewarding," says Sugrue. "There are very few things that we do in medicine as satisfying as this."
Some patients experience side effects from HIFU, such as imbalance, numbness or headaches, but the majority of these issues resolve within 30 days. Whitehead says he's had no adverse effects.
After receiving HIFU, all patients see immediate improvement with 80 to 90% tremor reduction, and while the procedure is relatively new, longer term follow-up studies show that tremor reduction remains at 70% five years after the treatment.
In January 2023, the Food and Drug Administration approved the use of HIFU on both sides of the brain in two procedures performed at least nine months apart. Previously, Sugrue explains, patients could have the procedure on only one side, out of concern for side effects.
Sugrue thinks the success of HIFU in treating ET is the tip of the iceberg in terms of clinical uses for the technology. "I really think this is the first step in what will be a much broader application of ultrasound in neuroscience," he says. "That's one of the things to me that's particularly exciting about it."
Immediately following his treatment, Whitehead was able to use his right hand to sip from a water bottle without spilling and steadily put a pen to paper. "For the first time in years, I wrote my name like it was on my driver's license," he says.
After returning home, he's more comfortable being active and social with Millie, his wife of more than 50 years, by his side.
"You feel a lot more at ease when you're visiting with people – you don't want your tremors distracting from what you're doing," he says. "It was a great experience. It changed my life."
