MRI-guided focused ultrasound thalamotomy effectively reduces essential tremor in treatment-refractory patients, according to data published in the New England Journal of Medicine.1
Despite being the most common movement disorder, only about 50% of patients with essential tremor respond to first-line treatment with primidone or propranolol.2,3 Those who develop side effects or are resistant to treatment have the option of neurosurgical intervention: targeting of the nucleus ventralis intermedius of the thalamus through deep brain stimulation or radiofrequency thalamotomy.2,4 However, this option is often not a consideration for many patients due to the invasiveness of the procedures.
Previous pilot studies for use of MRI-guided focused ultrasound thalamotomy have shown promising results.5-7 In the current study, researchers conducted a prospective, sham-controlled trial of MRI-guided focused ultrasound thalamotomy in 76 patients with medication-refractory essential tremor.
Participants were assessed at baseline and 1, 3, 6, and 12 months after treatment based on the CRST and Quality of Life in Essential Tremor Questionnaire (QUEST), with the primary endpoint being the change in hand tremor score from baseline to 3 months. Participants included in the study had moderate to severe intention or postural tremor of the hand despite at least 2 medication trials. Participants with unstable cardiac disease, deep vein thrombosis risk factors, coagulopathies, neurodegenerative disease, cognitive impairment, or severe depression were excluded. The participants and assessing neurologists were blinded to the group assignments; however, the treatment team was not.
At the 3 month assessment, the investigators observed a 47% improvement in the mean score for hand tremor in the treatment group compared to 0.1% in the sham group (between-group difference = 8.3 points; 95% CI: 5.9 to 10.7, P < .001). The treatment group had persistent improvement through month 12, resulting in an approximate 40% improvement from baseline (mean score of 18.1±4.8 to 10.9±4.5; 7.2 points, 95% CI: 6.1 to 8.3, P < .001).
After the 3 month blinded period, 19 patients from the sham group and 2 participants from the treatment group with incomplete procedures underwent treatment. This group demonstrated a 55% and 52% improvement at 3 and 6 months, respectively (P < .001 for both). Mean CRST tremor scores improved by 41% at 3 months (50.1±14.0 at baseline to 29.6±13) and by 35% at 12 months (50.1±14.0 to 32.4±14.5).
Participants in the treatment group reported significant improvements in total disability and quality of life compared with the sham group (62% reduction vs 3%, P < .001; 46% reduction vs 3%, P < .001) from baseline to 3 months, with improvement sustained through 12 months.
Notably, numbness or paresthesias and gait disturbance was reported in 38% and 36% of treatment participants, respectively, with some reporting persistent symptoms at 12 months (14% and 9%, respectively). The investigators noted that the adverse effects seemed to peak the first week after treatment and were related to the lesion size and surrounding edema.
“MRI imaging and thermometry provide a high level of control during focused ultrasound thalamotomy,” lead author W. Jeffrey Elias, MD, of the University of Virginia in Charlottesville, said in a press release.8 “Importantly, before treatment, adjustments can be made based on intraoperative imaging and clinical feedback from the patient, contributing to a safe procedure.”
Disclosures: Drs Elias, Ghanouni, Butts Pauly, Lozano, and Cosgrove report grant support from InSightec; Drs Elias and Lipsman report receiving grant support and fees from the Focused Ultrasound Foundation; Drs Ghanouni and Butts Pauly report receiving grant support from GE Healthcare; Dr Hynynen reports receiving royalties from an ultrasound therapy patent (US6770031 B2); Dr Gwinn reports receiving teaching fees from NeuroPace and Boston Scientific; and Dr Taira reports receiving lecture fees from Daiichi-Sankyo, Eisai, GlaxoSmithKline, Otsuka, Pfizer, Hisamitsu, Dainippon-Sumitomo, Takeda, and Kyowa-Hakko, and grant support from St. Jude Medical. The study was supported by the Binational Industrial Research and Development Foundation, the Focused Ultrasound Foundation, and InSightec. The focused ultrasound system used for the treatment group was manufactured by InSightec, who was also involved in the oversight of the study.
- Elias WJ, Lipsman N, Ondo WG, et al. A randomized trial of focused ultrasound thalamotomy for essential tremor. N Engl J Med. 2016;375(8):730-9.
- Deuschl G, Raethjen J, Hellriegel H, Elble R. Treatment of patients with essential tremor. Lancet Neurol. 2011;10:148-61.
- Zesiewicz TA, Elble R, Louis ED, et al. Practice parameter: therapies for essential tremor: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2005;64:2008-20.
- Ho AL, Erickson-Direnzo E, Pendharkar AV, Sung CK, Halpern CH. Deep brain stimulation for vocal tremor: a comprehensive, multidisciplinary methodology. Neurosurg Focus. 2015;38(6):E6.
- Chang WS, Jung HH, Kweon EJ, Zadicario E, Rachmilevitch I, Chang JW. Unilateral magnetic resonance guided focused ultrasound thalamotomy for essential tremor: practices and clinicoradiological outcomes. J Neurol Neurosurg Psychiatry. 2015;86:257-64.
- Elias WJ, Huss D, Voss T, et al. A pilot study of focused ultrasound thalamotomy for essential tremor. N Engl J Med. 2013; 369:640-8.
- Lipsman N, Schwartz ML, Huang Y, et al. MR-guided focused ultrasound thalamotomy for essential tremor: a proof-ofconcept study. Lancet Neurol. 2013;12: 462-8.
- Pivotal Study Results Published In New England Journal Of Medicine (NEJM) Confirm Safety And Efficacy Of Insightec’s Exablate Neuro System For The Treatment Of Essential Tremor [Press Release]. InSightec Newsroom; August 25, 2016.