Focused ultrasound (FUS) is a specialized technique that was FDA approved to treat essential tremor (ET) in 2016. Patients undergoing treatment receive a noninvasive MRI-guided procedure in which there is no incision, no breach of the skull as in deep brain stimulation (DBS). Instead, beams of acoustic energy are directed from 1,024 tiny transducers toward the same target in the brain, the VIM nucleus of the thalamus. Ultrasound energy combines at the VIM to lesion the nucleus by generating heat powerful enough to coagulate (and thus destroy) tissue. The result is similar to any intervention that burns, freezes, or otherwise jams the signal in a brain region (much of the programming of DBS for example, is meant to jam a signal). As of yet, with ET only one side is treated by FUS.
HOW EFFECTIVE IS FUS FOR ET?
In a major U.S. study involving 76 patients with medication-refractory ET, a 32-point clinical tremor rating scale was used to measure outcomes (1). Hand tremor scores improved after FUS, from 18.1 at baseline to 9.6 three months after the procedure. In other words, on average, tremor intensity lessened by about 50%. Patients receiving a sham procedure averaged a drop from 16.0 to 15.8 points. However, about 14% of the patients had a less than 20% improvement. At three months, adverse events in the treatment group included gait disturbance (36%) and tingling/numbness (38%). Slurred speech occurred in 1% of treated patients, but this apparently resolved. At 12 months, gait disturbance was still present in 9% and tingling in 14%. Overall, in the treatment group, disability was reduced by about 60% and about half of patients reported improvements in quality of life, which were maintained for the entire year of the study.
WHAT ABOUT FUS FOR PD?
In another trial (2), 30 patients with severe medication-resistant tremor underwent FUS: 18 with ET, 9 with PD, and 3 with both ET and PD. The average age of the study population was 68.9 ± 8.3 years, with an average disease duration of 12.1 ± 8.9 years. Patients with PD showed an average reduction in motor score (part III of the Unified Parkinson’s Disease Rating Scale) from 24.9 ± 8.0 to 16.4 ± 11 at one month, and 13.4 ± 9.2 at six months after treatment. Over the two- year follow up, tremor reappeared in two of the PD patients and in two who had combined ET-PD. In this study, reportedly no adverse event lasted beyond three months.
There are other considerations, and as of yet there is no FDA approval for PD. At the annual meeting of the American Academy of Neurology (AAN) held this past spring in Boston, the topic of FUS in PD was discussed (3). Dr. Paul Fishman noted that while some results were very positive in studies, going through the procedure itself might be uncomfortable. Some patients felt like the metal frame required for the procedure was uncomfortable, and many complained of a feeling of heat or sense of “whirling.” Since the original study, another 186 patients have been followed in open label studies of FUS. According to Dr. Fishman, 83% of adverse events were rated as mild and 2% as severe. Some of the adverse events had been persistent, and he noted, “This is not a risk-free technique,” though the overall incidence of serious adverse events was less than that of DBS. Dr. Michael Okun also spoke at the AAN meeting on this topic. By comparison, during DBS implantation a specialist is able to verify that the lead is in the exact right target of the brain; whereas “with ultrasound you cannot test to make sure you have hit the right target. If you have adverse events that include paresthesias in the face, tongue and leg, you missed.” There is also data showing that tremor may, more or less, “creep” back in the months after a FUS. More concerning, he noted,
“You can’t troubleshoot an ultrasound lesion. When you have a problem, you’ve got a problem. The lesion is irreversible. It can’t be programmed or modulated.“
The opposite is true of DBS, wherein programming changes can often alleviate a particular symptom.
In September 2015, Kimberly Spletter of Maryland was one of the first PD patients to receive FUS, and was featured on Michael J. Fox Mobile News (5). There is a 5-minute video on the site with some impressive before/after footage and interesting graphics. In Spletter’s case, the indication was not tremor, but her advanced dyskinesias (6). For this, a different target was chosen for FUS, the globus pallidus. She was one of forty patients were enrolled in a study of FUS in PD. It is my understanding that the study is completed, but the data is not yet published. To see an follow up video of her in January, 2017 click this link: http://www.localdvm.com/news/maryland/more-than-a-year-after-breakthrough-parkinsons-disease-treatment-woman-does-better-than-expected/642454168
WHAT ABOUT MAINE?
As for FUS in Maine, we are yet to have a case done here. I spoke with functional neurosurgeon Dr. Anand Rughani on the topic, who gave the following statement:
“It is an interesting option to consider for lesioning. The concept of lesioning is not new in treating movement disorders such as essential tremor and Parkinson’s disease. A lesion in the thalamus, for example, is called a thalamotomy, and has been widely used to treat tremor. Other methods of creating a lesion include radiosurgery using Gamma Knife, which is not an actual surgery, and radiofrequency lesioning, which is an actual surgery. In general, a few comments can be made when comparing lesioning to stimulation, as in deep brain stimulation. Lesions can only be done on one side of the brain. Lesions are not usually as durable as stimulation, meaning that the benefit may not last as long. The side effects of lesions are not reversible in the same way that they can be with stimulation. While there is now FDA approval for the treatment of essential tremor using focused ultrasound in the US, patients with Parkinson’s disease will need to consider this option through participation in an experimental trial.”
FUS is done in a few academic centers, such as Brigham and Women’s in Boston (4). On the BW Neurosurgery website, the following key considerations are listed: currently, insurance plans do not cover this procedure, and not everyone is eligible for focused ultrasound; eligibility requires evaluation by a neurologist and a neurosurgeon. One consideration is skull thickness; too much is not good for FUS. Senator Anthony Pollina of Vermont, for example, was disqualified from FUS for his PD for this reason, and opted instead for DBS (7).
Thus, there is a lot to be hopeful about with this new procedure, but it will be some time before it is available in Maine. More data needs to be collected, and FDA approval given. Still, over time it is likely that the procedure will continue to be refined and advanced.
REFERENCES
- Elias, et al., A Randomized Trial of Focused Ultrasound Thalamotomy for Essential Tremor. N Engl J Med. 2016;375(8):730-9.
- ZAaroor, et al. Magnetic resonance-guided focused ultrasound thalamotomy for tremor: a report of 30 Parkinson’s disease and essential tremor cases. J Neurosurg. 2017 Feb 24:1-9.
- Susman, E. Pro and Con: Is Focused ultrasound More Effective than DBS for Parkinson’s Disease? Neurology Today. 2017;17(1):34-5.
- http://www.brighamandwomens.org/Departments_and_Services/neurosurgery/NeurosurgicalTechnology/default.aspx?sub=1
- https://www.michaeljfox.org/mobile/news-detail.php?how-focused-ultrasound-helped-my-dyskinesia-from-parkinson
- https://www.michaeljfox.org/foundation/news-detail.php?first-patient-treated-in-dyskinesia-study-using-ultrasound-technology
- https://vtdigger.org/2017/01/16/digger-dialogue-surgery-gives-sen-anthony-pollina-new-lease-life/#.Wclu3VtSyM9
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