Focused Ultrasound for Parkinson's Tremor: An Update

Focused Ultrasound (FUS) therapy, which employs ultrasound waves to create targeted zones of therapeutic thermal injury, has been investigated in the treatment of essential tremor and in Parkinson’s disease associated tremor. The Focused Ultrasound Foundation (FUSF) recently announced the start of a Phase III study, which will be funded through a public-philanthropy-industry collaboration between the FUSF, InSightec and the US-Israel Binational Industry R&D. Foundation, to further explore the efficacy of FUS therapy in essential tremor. The trial will involve 72 patients at up to eight sites around the world, including The University of Virginia, Swedish Medical Center in Seattle, and Stanford University. Results of the study are expected to support a submission for Pre- Market Approval (PMA) and could pave the way for studying other neurological conditions.

On the heels of a successful pilot study of FUS therapy for tremor in Parkinson’s, the FUSF also announced that it has received a $600,000 grant from The Michael J. Fox Foundation for Parkinson’s Research (MJFF) to help fund a pilot study to determine the feasibility, safety, and preliminary efficacy of magnetic resonance-guided focused ultrasound for the treatment of dyskinesia in Parkinson’s disease.

Ahead, Binit B. Shah, MD, Assistant Professor, Neurology, Parkinson’s Disease and Movement Disorders Division at University of Virginia, talks about the use of FUS therapy for essential tremor and in the treatment of PD associated tremor.

What is FUS therapy and how is it being used in different forms of tremor?

Dr. Shah: When it comes to Focused Ultrasound therapy for tremor, we are talking about a helmet apparatus that contains about a thousand elements that each has an ultrasound transducer. Where the focus is, we can track the increase in temperature using MRI guidance and MR thermometry to see where it’s having an effect or where we’re targeting.

When it comes to tremor, our understanding of tremor is really in the tremor pathways in the brain—which parts of the brain are involved in the tremor circuitry. Where they’re not structurally abnormal, necessarily, we know that they are carrying tremor signals in the neuronal firing patterns.

If we can interrupt those pathways anywhere along that circuit and particularly a part of the brain called the ventral intermediate (VIM) nucleus of the thalamus we can reduce or completely abate tremor.

What is the evidence for FUS therapy for tremor?

Dr. Shah: The majority of the reports that we have are smaller series. At UVA we have the largest series, which is 15 patients, all of whom have completed a year of follow up and some of whom have gotten past two years. The main outcome we’ve looked at is safety first of all—and that’s typically the case with any new treatment paradigm—“Is this safe?”—and then secondly, “Is this effective?” And certainly when we’re talking about lesions in the brain that’s a paramount concern.

The safety profile has been favorable. There have been some patients out of those 15 who had immediate side effects, such as instability or the feeling of some numbness or tingling particularly around the mouth or in the hand that’s being treated for tremor. But the vast majority had improved within a couple of weeks. What was left at one year was a single patient out of those 15 who was left with a bit of tingling along the aspect of their forefinger in the treated hand.

In terms of efficacy, we found quite a significant reduction in 14 of the 15 patients where there was over a 50 percent reduction in the rating scales, as we measured them using the clinical rating scale in tremor. Some of the patients had almost near resolution of tremor that’s been persistent for a year to two years.

Probably just as importantly, the quality of life scales have also had really quite remarkable benefit that’s persisted for the year to two years, as well as a simulated eating test that showed a lot of improvement as well.

What are potential benefits of FUS therapy for Parkinson’s related tremor?

Dr. Shah: Since we’re using the FUS energy to create a thermal lesions it’s really a one-time procedure. It’s a single treatment and that in and of itself is attractive to a lot of patients.

Tremor ends up often being this particularly outlying symptom that can be more difficult in a certain subset of Parkinson’s patients to get control of. Our thought is that we have the tremor pathway that is fairly well defined, not only in essential tremor but also has an analogue in Parkinson’s disease. We can potentially use the same target— the VIM nucleus of the thalamus—in the essential tremor trial and use that for these tremor dominant, medication- refractory Parkinson’s patients, knowing that the other features of the Parkinson’s either aren’t very prominent or are adequately being treated with the medications they are on to begin with.

Based on experience thus far, who are expected to be ideal candidates for FUS therapy for tremor?

Dr. Shah: There are a couple of disparate groups of people who could be good candidates for this treatment. People who are disabled by a tremor where medication often fails to benefit them, particularly in their dominant arm, would be ideal candidates. The failure rate of medical treatment for essential tremor is really not acceptable—anywhere from 20 to 50 percent of patients with essential tremor, which is a fairly common disorder, don’t get satisfactory response with their medications.

Then there’s also a category of patients in whom the traditional treatments we have incur probably or will be shown to incur a little higher of a risk than we would expect to see with focused ultrasound in terms of patients who may be debilitated due to other medical illnesses of even neurological illness that still have a medication refractory tremor.

In Parkinson’s we have a lot of tremor-dominant folks who are really disabled by the tremor, and the other features of Parkinson’s are fairly well-controlled, and they are otherwise healthy. This could be a modality that’s really perfect for them in terms of being able to treat the symptom that’s most problematic and effectively treat it without necessarily interfering with their control of the other symptoms. Then, also, Parkinson’s is progressive and really can impact all of the neurologic functions of the brain to some degree, so in those individuals in whom the tremor is really the limiting factor in being able to feed themselves or dress themselves or do some of the tasks that they may be able to do even if their ambulation is limited or their mobility is limited for other reasons, that could really have a meaningful impact on those patients.

Hear the full interview, including an assessment of the relative risks and benefits of FUS therapy at PracticalNeurology.com.