TAN received an invitation from the Focused Ultrasound Foundation to participate in the live streaming of the 5th International Symposium in Bethesda, MD. It was an opportunity for our organization to tune into clinical presentations on movement disorders.
The movement disorders clinical session on August 29 began ahead of schedule, moderated by Kullervo Hynynen, MSc, PhD, and Howard Eisenberg, MD. Dr. Hynynen received the Focused Ultrasound Foundation 2016 Visionary Award. TAN was most interested in speakers whose Focused Ultrasound (FUS) presentations addressed essential tremor (ET).
- W. Jeff Elias University of Virginia
- Dr. Menashe Zaaroor Rambam health care campus
- Jonathon Parker Stanford University
- Vibhor Krishna The Ohio State University
TAN’s mission is to spread awareness of ET, but knowing that Parkinson’s (PD) like ET is a movement disorder with the symptom of tremor, we took notes on the 2 FUS presentations for the treatment of PD.
Essential Tremor FUS Presentations
Dr. Elias’ presentation highlighted his Facebook conversation on August 25, and his international (August 25, 2016) and pilot (August 15, 2013) studies published in the New England Journal of Medicine.
It would be redundant to restate Dr. Elias’ presentation that parallels the Facebook and NEJM links, with the exception of Dr. Elias being pleased with the 60% dramatic reduction in patients total disability score, and that the most improved quality of life for FUS patients is psychosocial.
Dr. Elias did comment that a more conservative lesioning process was used in the 15 patients that participated in the pilot study, and this may be why there has been a “wearing off” (Dr. Elias’ term) after 12 months.
Dr. Zaaroor followed with an excellent slide presentation. In contrast to Dr. Elias’ International multi-center 2 tiered study that included a double-blind design, Dr. Zaaroor conducted 44 consecutive cases in one national location (Haifa, Israel), and in addition to 23 essential tremor patients included 17 Parkinson’s patients as well as 3 dual diagnosis essential tremor and Parkinson’s patients and 1 Multiple Sclerosis patient. Tremor relief was immediate in all patients with the exception of one PD patient whose tremor was modified but did not stop like the others. According to Dr. Zaaroor, adjusting the target in small steps (0.1-0.5 mm) in accordance with the VIM somatotopic representation stopped tremor in other body parts beside the tremor in the treated hand. Leg and/or jaw tremor were stopped in 9 out of 12 patients with additional body part tremors, and one patient with eyes blinking showed a successful cessation. Dr. Zaaroor shared the video of when this patient realized their eyes stopped blinking. It was an “Oh My” moment.
Intraprocedural adjustments include varying the energy, the temperature, and the number of sonications.
Unlike Dr. Elias’ trials, where adverse events (sensory and gait) continued at 12 months, Dr. Zaaroor’s patients did not experience side effects that lasted so long. Perhaps this has to do with the lesioning process. One of Dr. Zaaroor’s slides indicated that the target can be adjusted at higher temperatures “to control complete elimination of tremor in the treated hand, additional tremulous body parts or to avoid adverse events.”
Dr. Zaaroor listed 14 side effects in relation to sonication, thalamotomy, and stereotatic frame. Side effects during sonication (headache, vertigo, dizziness, nausea, burning scalp sensation, vomiting and lip paresthesia) stopped in seconds and minutes. Side effects from thalamotomy (gait ataxia, unsteady feeling, taste disturbance, asthenia and hand ataxia) stopped in weeks, with the exception of gait ataxia and taste disturbance taking up to 3 months. Side effects from stereotactic frame (scalp numbness and hematoma near the eye) took a few weeks. In summary, side effects were transient and none lasted after 3 months.
Tremor recurrence was noted during the follow-up. In 3 ET, 2 PD, 2 ET-PD and the 1 MS patient, tremor emerged in 6 months time, but in all but 2 patients the tremor was less disabling. The reemergence of tremor did not affect all activities of daily living. Writing seemed to be the most affected ADL. 95.5% (42 out of 44) of the patients were satisfied with undergoing FUS.
Dr. Zaaroor presented recommendation slides. Noteworthy are:
- Use the same surgical targets that are used for DBS (STN and GPi) for better FUS treatment of PD and dystonia.
- Do not consider performing FUS on patients whose skull density ratio (SDR) is greater than 0.35.
- Identify and specifically target different tremor components.
Dr. Jonathan Parker’s presentation intrigued TAN because neither Dr. Elias nor Dr. Zaaroor offered an estimated FUS cost for ET. Dr. Elias commented that a cost should be available soon in association with FDA approval.
Dr. Elias is cautious in comparing FUS with DBS. His remarks are respectful because as he pointed out there is no DBS control at this time to make a procedural comparison. Dr. Elias’ brief statements consisted of:
- FUS is lesion control v DBS stimulation.
- There are no infections with FUS because it doesn’t use hardware or drill holes in the skull like DBS.
- Both procedures control tremor.
Dr. Parker’s topic focused on a cost-effectiveness analysis comparing FUS with Deep Brain Stimulation (DBS) and Stereotactic Radiosurgery (SRS). “Medicare reimbursements were collected as a proxy for societal cost, and FUS costs for ET were derived from a combination of available costs of approved indications and SRS costs where appropriate.”
The “meta-analytic techniques” implemented by Dr. Parker indicate that FUS ADL utility scores are higher when compared with DBS and SRS, based on Medicare reimbursement estimates. This suggests that the FUS procedure may have the highest effectiveness with the least cost. Dr. Parker provided Medicare reimbursement figures of $27,00 to $43,000 for DBS, and $18,000 for FUS. Two members of the audience challenged real costs, because DBS is usually bilateral and FUS at present is only unilateral. Dr. Parker handled the challenges well. TAN sent him an email, thanking him for his presentation.
Dr. Krishna, the fourth ET speaker, discussed his application of a novel direct targeting method, tractography-based identification that visualizes and accurately correlates with the VIM.The ventral intermediate nucleus (VIM) of the thalamus is the area that has to be precisely targeted for essential tremor control. The VIM is not visible on conventional MRI. Targeting with tractography was successful in 7 out of 8 patients that underwent FUS at Ohio State University. Tremor scores improved 1 month after the procedure. “None of the patients experienced sensory deficits or motor weakness during follow-up.”
Parkinson’s FUS Presentations
Dr. Bond was awarded a 2016 Young Investigator Award for his study on FUS treatment of tremor dominant Parkinson’s disease. 53 patients were screened for a randomized sham-controlled trial at the University of Virginia. Twenty-seven patients were enrolled and 6 were randomized for the sham procedure. There was a significant statistical and clinical reduction in hand tremor scores. There was a notable placebo effect in the PD sham patients, unlike no observable improvement in Dr. Elias’ ET sham patients. The placebo effect is consistent with a Parkinson’s phenomena. The conclusion was FUS can improve tremor-dominant PD hand tremor.
Dr. Chang, Honorary President of the FUS 5th International Symposium, presented a case study on 8 PD patients (4 males and 4 females) with drug-related dyskinesia who received FUS treatment at Severance Hospital in Korea. The follow up period was for 12 months. Dr. Chang shared a video that demonstrated FUS improvement in the control of dyskinesia. Dr. Chang concluded that FUS is functional neurosurgery that will continue to make changes to the neurological practice. However, there are challenging issues that will require more investigations. Dr, Chang emphasized the potential fields for FUS in addition to movement and pain disorders. He listed epileptic, psychiatric and memory disorders.
At the end of the day, the 2016 International Symposium on Focused Ultrasound set forth clinical goals by Symposium 2018.
- Repeat, Bilateral
Patient selection, skull related limitations reduced or eliminated
- Tremor dominant
Dyskinesia, pilot done, pivotal in progress
- Pilot in progress
- Tremor pilot in progress
TAN expresses its thanks to the Focused Ultrasound Foundation for making the live streaming of the 5th International Symposium available. The take-home message is tremor patients are the benefactors of FUS that is continually evolving to improve the treatment of movement disorders and other diseases.
TAN Blog Contributor