Essential Tremor Treatment Shows Promise

By Tracy Denninger

A pilot clinical trial at the University of Virginia has investigated the use of MR-guided focused ultrasound as a treatment for essential tremor.

For some older adults, the shaking that accompanies essential tremor (ET) can leave such patients helpless to perform many activities of daily living. But a new noninvasive procedure may provide them with hope—and relief from their symptoms.

Often misdiagnosed as Parkinson’s disease, ET affects roughly 10 million Americans, according to the International Essential Tremor Foundation. This neurological disorder is characterized by shaking of the hands, head, and voice and sometimes the legs and trunk.

While many cases of ET are mild, according to Neal Kassell, MD, chairman of the Focused Ultrasound Surgery Foundation, some patients suffer severely enough with the condition that they become disabled by the shaking. Fortunately, many people with ET require no treatment for their symptoms, and medication therapy, if needed, can help a good percentage of patients experience symptom control, Kassell says.

But for those with severe ET, invasive surgery may be their only option for symptom relief. One surgical procedure, radio-frequency thalamotomy, involves creating lesions deep in the brain to eliminate abnormal nerve cells, “which is traditionally done by making an incision and drilling into the skull and inserting an electrode, heating up the tip, and killing the cells,” Kassell says. Another option is deep brain stimulation, which involves implanting an electrode in the thalamus to help with controlling the tremors.

“The problem is these procedures are invasive, and many of these patients [those with severe ET] don’t want to have invasive procedures or can’t undergo them because of age or other medical conditions,” Kassell explains.

The good news for these ET patients is that a new procedure, MR-guided focused ultrasound, could provide a noninvasive means of relieving their symptoms.

After receiving funding from the Focused Ultrasound Surgery Foundation and approval from the FDA, a pilot clinical trial at the University of Virginia (UVA) investigated the use of MR-guided focused ultrasound as a treatment for essential tremor. Led by W. Jeffrey Elias, MD, a neurosurgeon and director of stereotactic and functional neurosurgery at UVA, the study treated 15 patients between February and December 2011. Thanks to promising results, the FDA has approved the treatment of 15 additional patients under the same clinical trial protocol.

Additionally, a parallel study involving six patients is being conducted at the University of Toronto, also with funding from the Focused Ultrasound Surgery Foundation.

According to Elias, the patient group treated during the first phase of the trial was a “relatively pure population,” meaning the subjects didn’t have Parkinson’s-like features or other conditions along with ET. “These people were very severely disabled with tremor, and all had difficulty with things such as feeding themselves, getting dressed, and writing,” Elias says. “Some patients are afraid to undergo [an invasive] surgical procedure, and many of them are just sitting at home living with their disability. They don’t die from tremor, but it’s extremely debilitating.”

Patient Selection and Treatment
To be selected for this MR-guided focused ultrasound trial, patients with ET went to a multidisciplinary movement disorder clinic, according to Elias. Movement disorder neurologists evaluated them and clinically diagnosed ET by performing extensive comprehensive testing of the patients’ tremor to assign a quantitative score and assess functional limitations and disabilities, Elias explains. They also underwent an MRI to rule out other neurodegenerative conditions.

The procedure, essentially a focused ultrasound thalamotomy, involved administering a series of focused ultrasound pulses through the patient’s scalp and skull to a specific spot in the thalamus known as the ventral intermediate nucleus. “The ultrasound transducer is MR compatible, so it’s inside the MRI machine. And while it’s sonocating the brain, we’re watching the treatment on the MRI so we can kind of confirm the treatment is precise in location and grade the intensity of the treatment,” Elias says. “The patient is also awake during the procedure, and this provides [a measure of] safety because they can respond.

“This technology combines the best of MRI for a diagnostic visualization of the brain as well as the ultrasound for the therapeutic aspects,” Elias says. “It’s a novel feature to be able to watch treatment as it’s being delivered.”

The procedure takes approximately three hours to perform, though Elias hopes that as it is refined and technology continues to advance, it will require less time. The patients were hospitalized overnight and then underwent extensive evaluations at one day, one week, one month, and three months after the procedure.

“We hope to have a safe and effective noninvasive option for people and hope to study using this treatment with other disorders,” Elias says.

“If, after larger definitive trials, it is approved for widespread use, this could be a good treatment for patients who have failed medication or who can’t or don’t want to have an invasive procedure. It could be a good alternative to deep brain stimulation and radio-frequency procedures,” Kassell says.

For more information about the UVA study, e-mail FUSbrain@virginia.edu. Comprehensive information about MR-guided focused ultrasound and its use in treating essential tremor can be found at www.fusfoundation.org/Essential-Tremor/essential-tremor.

— Tracy Denninger is senior production editor at Aging Well.