A randomized trial of focused ultrasound thalamotomy for essential tremor

W. Jeffrey Elias, Nir Lipsman, William G. Ondo, Pejman Ghanouni, Young G. Kim, Wonhee Lee, Michael Schwartz, Kullervo Hynynen, Andres M. Lozano, Binit B. Shah, Diane Huss, Robert F. Dallapiazza, Ryder Gwinn, Jennifer Witt, Susie Ro, Howard M. Eisenberg, Paul S. Fishman, Dheeraj Gandhi, Casey H. Halpern, Rosalind ChuangKim Butts Pauly, Travis S. Tierney, Michael T. Hayes, G. Rees Cosgrove, Toshio Yamaguchi, Keiichi Abe, Takaomi Taira, Jin W. Chang

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: Uncontrolled pilot studies have suggested the efficacy of focused ultrasound thalamotomy with magnetic resonance imaging (MRI) guidance for the treatment of essential tremor. METHODS: We enrolled patients with moderate-to-severe essential tremor that had not responded to at least two trials of medical therapy and randomly assigned them in a 3:1 ratio to undergo unilateral focused ultrasound thalamotomy or a sham procedure. The Clinical Rating Scale for Tremor and the Quality of Life in Essential Tremor Questionnaire were administered at baseline and at 1, 3, 6, and 12 months. Tremor assessments were videotaped and rated by an independent group of neurologists who were unaware of the treatment assignments. The primary outcome was the betweengroup difference in the change from baseline to 3 months in hand tremor, rated on a 32-point scale (with higher scores indicating more severe tremor). After 3 months, patients in the sham-procedure group could cross over to active treatment (the openlabel extension cohort). RESULTS: Seventy-six patients were included in the analysis. Hand-tremor scores improved more after focused ultrasound thalamotomy (from 18.1 points at baseline to 9.6 at 3 months) than after the sham procedure (from 16.0 to 15.8 points); the between-group difference in the mean change was 8.3 points (95% confidence interval [CI], 5.9 to 10.7; P<0.001). The improvement in the thalamotomy group was maintained at 12 months (change from baseline, 7.2 points; 95% CI, 6.1 to 8.3). Secondary outcome measures assessing disability and quality of life also improved with active treatment (the blinded thalamotomy cohort)as compared with the sham procedure (P<0.001 for both comparisons). Adverse events in the thalamotomy group included gait disturbance in 36% of patients and paresthesias or numbness in 38%; these adverse events persisted at 12 months in 9% and 14% of patients, respectively. CONCLUSIONS: MRI-guided focused ultrasound thalamotomy reduced hand tremor in patients with essential tremor. Side effects included sensory and gait disturbances.

Original languageEnglish
Pages (from-to)730-739
Number of pages10
JournalNew England Journal of Medicine
Volume375
Issue number8
DOIs
Publication statusPublished - 2016 Aug 25

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Essential Tremor
Tremor
Hand
Gait
Quality of Life
Magnetic Resonance Imaging
Confidence Intervals
Therapeutics
Hypesthesia
Paresthesia
Outcome Assessment (Health Care)

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Elias, W. Jeffrey ; Lipsman, Nir ; Ondo, William G. ; Ghanouni, Pejman ; Kim, Young G. ; Lee, Wonhee ; Schwartz, Michael ; Hynynen, Kullervo ; Lozano, Andres M. ; Shah, Binit B. ; Huss, Diane ; Dallapiazza, Robert F. ; Gwinn, Ryder ; Witt, Jennifer ; Ro, Susie ; Eisenberg, Howard M. ; Fishman, Paul S. ; Gandhi, Dheeraj ; Halpern, Casey H. ; Chuang, Rosalind ; Pauly, Kim Butts ; Tierney, Travis S. ; Hayes, Michael T. ; Cosgrove, G. Rees ; Yamaguchi, Toshio ; Abe, Keiichi ; Taira, Takaomi ; Chang, Jin W. / A randomized trial of focused ultrasound thalamotomy for essential tremor. In: New England Journal of Medicine. 2016 ; Vol. 375, No. 8. pp. 730-739.
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abstract = "BACKGROUND: Uncontrolled pilot studies have suggested the efficacy of focused ultrasound thalamotomy with magnetic resonance imaging (MRI) guidance for the treatment of essential tremor. METHODS: We enrolled patients with moderate-to-severe essential tremor that had not responded to at least two trials of medical therapy and randomly assigned them in a 3:1 ratio to undergo unilateral focused ultrasound thalamotomy or a sham procedure. The Clinical Rating Scale for Tremor and the Quality of Life in Essential Tremor Questionnaire were administered at baseline and at 1, 3, 6, and 12 months. Tremor assessments were videotaped and rated by an independent group of neurologists who were unaware of the treatment assignments. The primary outcome was the betweengroup difference in the change from baseline to 3 months in hand tremor, rated on a 32-point scale (with higher scores indicating more severe tremor). After 3 months, patients in the sham-procedure group could cross over to active treatment (the openlabel extension cohort). RESULTS: Seventy-six patients were included in the analysis. Hand-tremor scores improved more after focused ultrasound thalamotomy (from 18.1 points at baseline to 9.6 at 3 months) than after the sham procedure (from 16.0 to 15.8 points); the between-group difference in the mean change was 8.3 points (95{\%} confidence interval [CI], 5.9 to 10.7; P<0.001). The improvement in the thalamotomy group was maintained at 12 months (change from baseline, 7.2 points; 95{\%} CI, 6.1 to 8.3). Secondary outcome measures assessing disability and quality of life also improved with active treatment (the blinded thalamotomy cohort)as compared with the sham procedure (P<0.001 for both comparisons). Adverse events in the thalamotomy group included gait disturbance in 36{\%} of patients and paresthesias or numbness in 38{\%}; these adverse events persisted at 12 months in 9{\%} and 14{\%} of patients, respectively. CONCLUSIONS: MRI-guided focused ultrasound thalamotomy reduced hand tremor in patients with essential tremor. Side effects included sensory and gait disturbances.",
author = "Elias, {W. Jeffrey} and Nir Lipsman and Ondo, {William G.} and Pejman Ghanouni and Kim, {Young G.} and Wonhee Lee and Michael Schwartz and Kullervo Hynynen and Lozano, {Andres M.} and Shah, {Binit B.} and Diane Huss and Dallapiazza, {Robert F.} and Ryder Gwinn and Jennifer Witt and Susie Ro and Eisenberg, {Howard M.} and Fishman, {Paul S.} and Dheeraj Gandhi and Halpern, {Casey H.} and Rosalind Chuang and Pauly, {Kim Butts} and Tierney, {Travis S.} and Hayes, {Michael T.} and Cosgrove, {G. Rees} and Toshio Yamaguchi and Keiichi Abe and Takaomi Taira and Chang, {Jin W.}",
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Elias, WJ, Lipsman, N, Ondo, WG, Ghanouni, P, Kim, YG, Lee, W, Schwartz, M, Hynynen, K, Lozano, AM, Shah, BB, Huss, D, Dallapiazza, RF, Gwinn, R, Witt, J, Ro, S, Eisenberg, HM, Fishman, PS, Gandhi, D, Halpern, CH, Chuang, R, Pauly, KB, Tierney, TS, Hayes, MT, Cosgrove, GR, Yamaguchi, T, Abe, K, Taira, T & Chang, JW 2016, 'A randomized trial of focused ultrasound thalamotomy for essential tremor', New England Journal of Medicine, vol. 375, no. 8, pp. 730-739. https://doi.org/10.1056/NEJMoa1600159

A randomized trial of focused ultrasound thalamotomy for essential tremor. / Elias, W. Jeffrey; Lipsman, Nir; Ondo, William G.; Ghanouni, Pejman; Kim, Young G.; Lee, Wonhee; Schwartz, Michael; Hynynen, Kullervo; Lozano, Andres M.; Shah, Binit B.; Huss, Diane; Dallapiazza, Robert F.; Gwinn, Ryder; Witt, Jennifer; Ro, Susie; Eisenberg, Howard M.; Fishman, Paul S.; Gandhi, Dheeraj; Halpern, Casey H.; Chuang, Rosalind; Pauly, Kim Butts; Tierney, Travis S.; Hayes, Michael T.; Cosgrove, G. Rees; Yamaguchi, Toshio; Abe, Keiichi; Taira, Takaomi; Chang, Jin W.

In: New England Journal of Medicine, Vol. 375, No. 8, 25.08.2016, p. 730-739.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A randomized trial of focused ultrasound thalamotomy for essential tremor

AU - Elias, W. Jeffrey

AU - Lipsman, Nir

AU - Ondo, William G.

AU - Ghanouni, Pejman

AU - Kim, Young G.

AU - Lee, Wonhee

AU - Schwartz, Michael

AU - Hynynen, Kullervo

AU - Lozano, Andres M.

AU - Shah, Binit B.

AU - Huss, Diane

AU - Dallapiazza, Robert F.

AU - Gwinn, Ryder

AU - Witt, Jennifer

AU - Ro, Susie

AU - Eisenberg, Howard M.

AU - Fishman, Paul S.

AU - Gandhi, Dheeraj

AU - Halpern, Casey H.

AU - Chuang, Rosalind

AU - Pauly, Kim Butts

AU - Tierney, Travis S.

AU - Hayes, Michael T.

AU - Cosgrove, G. Rees

AU - Yamaguchi, Toshio

AU - Abe, Keiichi

AU - Taira, Takaomi

AU - Chang, Jin W.

PY - 2016/8/25

Y1 - 2016/8/25

N2 - BACKGROUND: Uncontrolled pilot studies have suggested the efficacy of focused ultrasound thalamotomy with magnetic resonance imaging (MRI) guidance for the treatment of essential tremor. METHODS: We enrolled patients with moderate-to-severe essential tremor that had not responded to at least two trials of medical therapy and randomly assigned them in a 3:1 ratio to undergo unilateral focused ultrasound thalamotomy or a sham procedure. The Clinical Rating Scale for Tremor and the Quality of Life in Essential Tremor Questionnaire were administered at baseline and at 1, 3, 6, and 12 months. Tremor assessments were videotaped and rated by an independent group of neurologists who were unaware of the treatment assignments. The primary outcome was the betweengroup difference in the change from baseline to 3 months in hand tremor, rated on a 32-point scale (with higher scores indicating more severe tremor). After 3 months, patients in the sham-procedure group could cross over to active treatment (the openlabel extension cohort). RESULTS: Seventy-six patients were included in the analysis. Hand-tremor scores improved more after focused ultrasound thalamotomy (from 18.1 points at baseline to 9.6 at 3 months) than after the sham procedure (from 16.0 to 15.8 points); the between-group difference in the mean change was 8.3 points (95% confidence interval [CI], 5.9 to 10.7; P<0.001). The improvement in the thalamotomy group was maintained at 12 months (change from baseline, 7.2 points; 95% CI, 6.1 to 8.3). Secondary outcome measures assessing disability and quality of life also improved with active treatment (the blinded thalamotomy cohort)as compared with the sham procedure (P<0.001 for both comparisons). Adverse events in the thalamotomy group included gait disturbance in 36% of patients and paresthesias or numbness in 38%; these adverse events persisted at 12 months in 9% and 14% of patients, respectively. CONCLUSIONS: MRI-guided focused ultrasound thalamotomy reduced hand tremor in patients with essential tremor. Side effects included sensory and gait disturbances.

AB - BACKGROUND: Uncontrolled pilot studies have suggested the efficacy of focused ultrasound thalamotomy with magnetic resonance imaging (MRI) guidance for the treatment of essential tremor. METHODS: We enrolled patients with moderate-to-severe essential tremor that had not responded to at least two trials of medical therapy and randomly assigned them in a 3:1 ratio to undergo unilateral focused ultrasound thalamotomy or a sham procedure. The Clinical Rating Scale for Tremor and the Quality of Life in Essential Tremor Questionnaire were administered at baseline and at 1, 3, 6, and 12 months. Tremor assessments were videotaped and rated by an independent group of neurologists who were unaware of the treatment assignments. The primary outcome was the betweengroup difference in the change from baseline to 3 months in hand tremor, rated on a 32-point scale (with higher scores indicating more severe tremor). After 3 months, patients in the sham-procedure group could cross over to active treatment (the openlabel extension cohort). RESULTS: Seventy-six patients were included in the analysis. Hand-tremor scores improved more after focused ultrasound thalamotomy (from 18.1 points at baseline to 9.6 at 3 months) than after the sham procedure (from 16.0 to 15.8 points); the between-group difference in the mean change was 8.3 points (95% confidence interval [CI], 5.9 to 10.7; P<0.001). The improvement in the thalamotomy group was maintained at 12 months (change from baseline, 7.2 points; 95% CI, 6.1 to 8.3). Secondary outcome measures assessing disability and quality of life also improved with active treatment (the blinded thalamotomy cohort)as compared with the sham procedure (P<0.001 for both comparisons). Adverse events in the thalamotomy group included gait disturbance in 36% of patients and paresthesias or numbness in 38%; these adverse events persisted at 12 months in 9% and 14% of patients, respectively. CONCLUSIONS: MRI-guided focused ultrasound thalamotomy reduced hand tremor in patients with essential tremor. Side effects included sensory and gait disturbances.

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Elias WJ, Lipsman N, Ondo WG, Ghanouni P, Kim YG, Lee W et al. A randomized trial of focused ultrasound thalamotomy for essential tremor. New England Journal of Medicine. 2016 Aug 25;375(8):730-739. https://doi.org/10.1056/NEJMoa1600159