The professor of neurology and chief of the Neurology Service at the Maryland VA Health Care System spoke about the impact focused ultrasound has had in the treatment of tremor-dominant Parkinson disease.
Paul Fishman, MD, PhD
In December 2018, the FDA approved the use of a focused ultrasound technology, Exablate Neuro, for the treatment of tremor-dominant Parkinson disease, providing these patients and their physicians another option for treating patients who don’t wish to undergo deep brain stimulation (DBS) implantation.
The treatment can target and ablate tissue in the brain with no surgical incisions, with MRI guiding the treatment’s planning and delivering thermal feedback for real-time monitoring, allowing for a personalized treatment plan. In a pilot trial of 27 participants with tremor-dominant Parkinson disease, on-medication Clinical Rating Scale for Tremor A+B subscores improved a median 7 points, or 62% (interquartile range [IQR], 22% to 79%) from a baseline of 17 points (IQR, 10.5 to 27.5), compared to 2 points, or 22% (IQR, -11% to 29%), from a baseline of 23 points (IQR, 14—27), a statistically significant difference. The on-medication median Unified Parkinson’s Disease Rating Scale motor scores improved 8 points (IQR, 0.5–11.0) compared to 1 point (IQR, −5.0 to 9.0) from a baseline of 25 points (IQR, 15.0–33) after sham procedures.
To find out more about the focused ultrasound treatment and its impact on the community following its FDA go-ahead, NeurologyLive spoke with Paul Fishman, MD, PhD, a professor of neurology and chief of the Neurology Service at the Maryland VA Health Care System.
Paul Fishman, MD, PhD: Well, it offers another option. DBS has been out there before, and I think it was really a hard decision for patients. In particular, these are people—in general—where their medical therapy, sometimes frequently, fails. Levodopa is a wonderful drug, but there are certain numbers of patients who are fairly resistant to it in terms of tremor. Tremor is not particularly a dopaminergic system-related symptom, and so it's not surprising that levodopa, the most effective medication for Parkinson, fails when patients have tremor as their predominant symptom. This may be a somewhat different phenotype of Parkinson than we generally think of, and they can be levodopa-resistant. Before, their only option really was DBS.
This, particularly, for those who are predominantly unilateral—and many of them are—and that involve the dominant hand, they certainly could opt for DBS. DBS done on 1 side of the brain has less risk than DBS done on both sides, but, again, it gives them another option.
It does require the technology and although there's no direct comparison yet, when I’ve looked at the essential tremor literature, the literature right now in terms of serious events says that even though focused ultrasound can commonly have, particularly a VIM, some adverse events or side effects, in terms of serious side effects FUS looks like it's safer. So, it gives them another option. Patients can look at that data. Again, there are no comparative trials yet, and it's hard comparing something that's been out there for 20 years to something that got FDA approved a few months ago, but in general, serious side effects with focused ultrasound are quite rare. We know we see them, but we see them more at a 1% rate, whereas in DBS, even in the best of hands in contemporary studies, you're up 3%, 4%, or more for serious events.
That it is FDA approved now. There was a lot of confusion and we have a bunch of patients waiting because when it got FDA approved for essential tremor, there was a great deal confusion about whether or not we could treat patients [with tremor-dominant Parkinson].
Remember, it is the same procedure—it's the same thalamic target, the patient experience is identical to that, and we got a lot of referrals thinking that we could go ahead and treat that. The idea was for many surgical procedures and for many medications, we commonly use them off-label. In this, off-label meant that we really would have to do that without the support of INSIGHTEC and the technical staff, and this is very technically demanding, complex technology. I don't think our group, or most groups, felt that it wasn't safe to say, “We're going to go and treat tremor-dominant Parkinson, it's the exact same procedure, and we're going to go on our own and treat them off-label.” I think most places in this country were unwilling to do it, so we accumulated them.
Also, the whole reason DAT scans exist is that there sometimes is confusion about diagnosis. What would happen, not rarely, is patients would be referred to me with a diagnosis of essential tremor—usually not by movement disorder specialist—and I had the uncomfortable experience of telling them that I thought they had tremor-dominant Parkinson. Sometimes, we verified that with a DAT scan, so again, there's some confusion over diagnosis.
Sadly, we're still in that period where there's a lag time between FDA approval and Medicare and insurance reimburses. We'll probably have to wait to see if Medicare, which varies from state to state and region to region, will approve for reimbursement for tremor-dominant Parkinson's disease.
Coverage is the biggest caveat. Some of the patients we're going to do right now were self-pay. They've been very eager, and we've accumulated these people because there was so much interest when it first came out for essential tremor, and there was either confusion about what we could treat and what we couldn't treat, and some of these people had a different diagnosis.
That is the biggest issue for all these things, and it may take a while. It took a while for essential tremor because of the whole issue of durability. Now, the upfront costs are less than DBS because remember, there's no device here. A typical treatment is expensive—it's $25,000—but it's substantially lower than DBS, which includes the device plus the whole procedure.
But the question is: what is the long-term cost? That is going to be dependent on whether or not patients need to be retreated in the future, and from essential tremor, we're seeing at least good durability in the 2- to 3-year range. But of course, DBS is known to have good durability for tremor control in the 5- to 10-year range. When people plan in terms of cost, they don't look at just the cost of the procedure, they look at the cost in terms of long-term impact for the patients as well. I imagine that it may be a while before insurers say they know how durable this is. The studies that are out there, some of the patients are out in the 1- or 2-year range, but it really took a while and there were a larger number of patients with essential tremor. There's published 2-year data and there's now 3-year data for essential tremor. That’s not yet back for a substantive number of Parkinson patients to say how long is this going to last, and you can analogize from essential tremor, but that's an analogy, not real data.
Transcript edited for clarity.
1. Bond A, Shah B, Huss, D, et al. Safety and Efficacy of Focused Ultrasound Thalamotomy for Patients With Medication-Refractory, Tremor-Dominant Parkinson Disease. JAMA Neurology. 2017;74(12):1412­—1418. doi: 10.1001/jamaneurol.2017.3098.