January/February 2016

Magnetic Resonance–Guided Focused Ultrasound Therapy for Essential Tremor
By Jaimie Lazare
Today's Geriatric Medicine
Vol. 9 No. 1 P. 31

A therapy using magnetic resonance (MR) to focus ultrasound waves in the brain shows promise in treating essential tremor (ET) in older adults.

ET is the most common type of movement disorder, and it affects approximately 7 million people in the United States.1 ET is an involuntary, rhythmic movement that affects the hands, arms, and head; the tremor can, in rare cases, involve lower parts of the body, such as the legs and feet.2 While ET is not fatal, the tremor can be a source of embarrassment and frustration.

Richard Schallhorn, vice president of neurosurgery products at InSightec, says there are many older patients with tremors; some of these patients can have tremors so significant that they're unable to drink from a cup, eat with a fork, or write.

Currently, there are no specific diagnostic tests for ET; however, the diagnosis for ET is determined by taking a thorough history, performing a physical exam, and ruling out other conditions such as Parkinson's disease that could be causing the tremor. ET has no cure; however, the neurological disorder can be managed with medication. The tremor progressively worsens and eventually no longer responds to medication. For treatment of medication-refractory tremor, surgical options are considered, such as deep brain stimulation that requires implanting a thin electrode in the brain. But brain surgery is a therapeutic option usually reserved for severe cases because of the inherent risks it carries, such as infection or complications of anesthesia.3

InSightec, the company behind the development of MR-guided focused ultrasound (MRgFUS) therapy, is conducting a clinical study to evaluate the efficacy of this noninvasive therapy in the treatment of ET. During the therapy, MR is used to precisely guide focused ultrasound waves to the affected area of the brain responsible for the tremor.

Schallhorn says the therapy is an opportunity to provide patients with a noninvasive treatment option that allows them to regain control of their hands or other areas of the body affected by the tremor.

MRgFUS Therapy
The Wexner Medical Center in Ohio is one of six centers across the nation to participate in the clinical trial. Physicians have enrolled and treated the first patient4 and are preparing to treat other study participants.

Eric Bourekas, MD, MBA, FACR, an associate professor of radiology, neurology, and neurological surgery, and chief of neuroradiology at the Ohio State University Wexner Medical Center in Columbus, explains that during the procedure "the patient is awake, and the hair has to be shaved because there's a water bath that is involved with the head coil of the ultrasound. Certain structures like the skull can heat up and that's not a desired effect."

Bourekas explains that a stereotactic frame is screwed onto the head, a process which involves the use of a local anesthetic. When the frame is in place, anchoring the ultrasound unit and ensuring there's no movement, the ultrasound unit is then attached to the frame and the water is turned on for cooling. Then MR imaging is initiated. When the targeted area is determined via MR, the ultrasound is turned on and ultrasound waves are used to progressively heat the targeted tissue, he says.

Schallhorn adds that MRgFUS therapy raises the temperature to about 60° C, which is substantial enough to destroy the targeted tissue. What's unique about the fundamental technology is the way in which ultrasound waves are focused inside the body; each beam goes through the body without causing damage. As the ultrasound waves are directed onto a focal point, the temperature is raised to a level high enough to destroy a precise area of brain tissue, Schallhorn says.

"Once the procedure is completed, the patient spends the night in the hospital. He or she undergoes a head CT [computed tomography] to make sure that we did not cause a bleed and to see the effects of what we did. The patient goes home the next day if all goes well," Bourekas says.

MRgFUS therapy has immediate effects and doesn't require follow-up treatments. So when the procedure is over, the tremors are gone, Bourekas says. He adds that any necessary adjustments are usually performed at the time of the original treatment.

Schallhorn notes that it is possible for a patient to return for additional treatment, if warranted. "One can be conservative with this treatment because if you're too aggressive and [if you] destroy a little too much tissue, there's no going back," he says.

From the standpoint that no surgical incision is being made in the skull, patients would be more likely to undergo the MRgFUS therapy again to improve the effect of the treatment, if necessary, he says. Schallhorn, however, emphasizes that the therapy works well as a one-time treatment and that those undergoing this procedure again would comprise only a small percentage of patients.

Maximal Benefits, Minimal Risks
"One of the things that's done is a CT that looks at the density of the skull. If the skull is anatomically too thick or too dense, then you're not able to generate enough heat and focus it enough so that it can have an effect of the treatment," Bourekas says.

Bourekas points out the importance of ensuring that the involuntary movement is attributed to ET and not Parkinson's disease or some other cause of a tremor. If it's not an ET, then the treatment may not have an effect on the tremor, he says.

When it comes to the risks of the procedure, Bourekas says, "You can cause bleeding, although it's uncommon. But you are basically destroying a small part of tissue. So you can get all kinds of transient effects. You can have speech abnormalities and paresthesias. You can affect people's motor skills. There are certainly potential complications, but they are not very high."

"Patients can have some neurological deficits, weakness, or tingling in certain parts of the body, mainly the fingers. The good news is that the vast majority of those effects are transient," Schallhorn says.

Schallhorn adds that there are few cases in which side effects have persisted. People who have reported these effects have tolerated them well, and those patients have expressed a willingness to undergo the procedure again, based on their results and their ability to perform many of the tasks that were difficult for them prior to the therapy, he says.

Waves of Therapeutic Potential
Bourekas says that despite the small number of patients and fairly limited experience with the technology, potential applications for the technology are plentiful. There are trials, Bourekas says, that are going on in Europe. Some of the research explores the use of the therapy to treat Parkinsonian tremors.5 The therapy is also being studied in epilepsy6 as a way to treat seizures by targeting tissue noninvasively, he says.

"The trial that we have going on right now is for essential tremor, [but] there's already work going on with Parkinson's disease, for brain tumors, and for epilepsy," Schallhorn says.

In an unprecedented procedure,7 Canadian researchers treated a patient with a brain tumor by using the focused ultrasound technology to deliver a chemotherapeutic drug, Schallhorn says. There are other ways in which the technology can be used besides raising the temperature to destroy tissue. The technology can also be used to disrupt blood vessels in a way that is not damaging to the vascular structure but allows drugs to pass through the brain, he adds.

Bourekas says that some researchers have even proposed the use of MRgFUS technology rather than gamma knife radiation surgery to treat vascular abnormalities such as cavernomas and arteriovenous malformations.

Although the technology is not approved for ET, Bourekas notes that the same technology used in the focused ultrasound for ET is approved for use elsewhere in the body, but it's a different unit. The FDA has approved the technology for use in the treatment of uterine fibroids since 2004 and more recently for pain palliation in metastatic bone disease, he says.

InSightec has submitted its premarket approval application to the FDA for use of the technology in the treatment of ET. Schallhorn says, "Once we have FDA approval, then the next step in the process would be to secure reimbursement coverage. It will take some time, but we are confident that based on the results [of the trial] that it will be approved."

— Jaimie Lazare is a freelance writer based in Brooklyn, New York.

References
1. Louis ED, Ottman R. How many people in the USA have essential tremor? Deriving a population estimate based on epidemiological data. Tremor Other Hyperkinet Mov (N Y). 2014;4:259.

2. Essential tremor. MedlinePlus website. https://www.nlm.nih.gov/medlineplus/ency/article/000762.htm. Updated May 20, 2014. Accessed November 19, 2015.

3. Brain surgery. MedlinePlus website. https://www.nlm.nih.gov/medlineplus/ency/article/003018.htm. Updated February 3, 2015. Accessed November 23, 2015.

4. Ohio State joins essential tremor trial. Focused Ultrasound Foundation website. http://www.fusfoundation.org/news/1666-ohio-state-joins-essential-tremor-trial. Accessed November 23, 2015.

5. Magara A, Bühler R, Moser D, Kowalski M, Pourtehrani P, Jeanmonod D. First experience with MR-guided focused ultrasound in the treatment of Parkinson's disease. J Ther Ultrasound. 2014;2:11.

6. Nowell M, Miserocchi A, McEvoy AW, Duncan JS. Advances in epilepsy surgery. J Neurol Neurosurg Psychiatry. 2014;85(11):1273-1279.

7. World first: blood-brain barrier opened non-invasively to deliver chemotherapy. Sunnybrook Health Sciences Centre website. http://sunnybrook.ca/media/item.asp?i=1351. Updated November 8, 2015. Accessed November 23, 2015.