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March 28, 2023; 100 (13) Research Article

Prospective Long-term Follow-up of Focused Ultrasound Unilateral Subthalamotomy for Parkinson Disease

View ORCID ProfileRaúl Martínez-Fernández, View ORCID ProfileElena Natera-Villalba, View ORCID ProfileJorge U. Máñez Miró, View ORCID ProfileRafael Rodriguez-Rojas, Marta Marta del Álamo, View ORCID ProfileJosé Ángel Pineda-Pardo, View ORCID ProfileClaudia Ammann, View ORCID ProfileIgnacio Obeso, View ORCID ProfileDavid Mata-Marín, Frida Hernández-Fernández, View ORCID ProfileCarmen Gasca-Salas, View ORCID ProfileMichele Matarazzo, Fernando Alonso-Frech, View ORCID ProfileJose A. Obeso
First published January 11, 2023, DOI: https://doi.org/10.1212/WNL.0000000000206771
Raúl Martínez-Fernández
From the HM CINAC (Centro Integral de Neurociencias Abarca Campal) (R.M.-F., E.N.-V., J.U.M.M., R.R.-R., M.D.A., J.A.P.-P., C.A., I.O., D.M.-M., F.H.-F., C.G.-S., M.M., F.A.-F., J.A.O.). Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid; CIBERNED (R.M.-F., R.R.-R., J.A.P.-P., I.O., C.G.-S., J.A.O.), Instituto Carlos III, Madrid; San Pablo-CEU University Medical School (R.M.-F., J.A.O.), Madrid, Spain. J.U.M.M. is currently at the Department of Neurology, IMED Hospitales, Valencia and the Universidad Autónoma de Madrid University-Instituto Cajal, Madrid, Spain.
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Elena Natera-Villalba
From the HM CINAC (Centro Integral de Neurociencias Abarca Campal) (R.M.-F., E.N.-V., J.U.M.M., R.R.-R., M.D.A., J.A.P.-P., C.A., I.O., D.M.-M., F.H.-F., C.G.-S., M.M., F.A.-F., J.A.O.). Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid; CIBERNED (R.M.-F., R.R.-R., J.A.P.-P., I.O., C.G.-S., J.A.O.), Instituto Carlos III, Madrid; San Pablo-CEU University Medical School (R.M.-F., J.A.O.), Madrid, Spain. J.U.M.M. is currently at the Department of Neurology, IMED Hospitales, Valencia and the Universidad Autónoma de Madrid University-Instituto Cajal, Madrid, Spain.
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Jorge U. Máñez Miró
From the HM CINAC (Centro Integral de Neurociencias Abarca Campal) (R.M.-F., E.N.-V., J.U.M.M., R.R.-R., M.D.A., J.A.P.-P., C.A., I.O., D.M.-M., F.H.-F., C.G.-S., M.M., F.A.-F., J.A.O.). Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid; CIBERNED (R.M.-F., R.R.-R., J.A.P.-P., I.O., C.G.-S., J.A.O.), Instituto Carlos III, Madrid; San Pablo-CEU University Medical School (R.M.-F., J.A.O.), Madrid, Spain. J.U.M.M. is currently at the Department of Neurology, IMED Hospitales, Valencia and the Universidad Autónoma de Madrid University-Instituto Cajal, Madrid, Spain.
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Rafael Rodriguez-Rojas
From the HM CINAC (Centro Integral de Neurociencias Abarca Campal) (R.M.-F., E.N.-V., J.U.M.M., R.R.-R., M.D.A., J.A.P.-P., C.A., I.O., D.M.-M., F.H.-F., C.G.-S., M.M., F.A.-F., J.A.O.). Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid; CIBERNED (R.M.-F., R.R.-R., J.A.P.-P., I.O., C.G.-S., J.A.O.), Instituto Carlos III, Madrid; San Pablo-CEU University Medical School (R.M.-F., J.A.O.), Madrid, Spain. J.U.M.M. is currently at the Department of Neurology, IMED Hospitales, Valencia and the Universidad Autónoma de Madrid University-Instituto Cajal, Madrid, Spain.
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Marta Marta del Álamo
From the HM CINAC (Centro Integral de Neurociencias Abarca Campal) (R.M.-F., E.N.-V., J.U.M.M., R.R.-R., M.D.A., J.A.P.-P., C.A., I.O., D.M.-M., F.H.-F., C.G.-S., M.M., F.A.-F., J.A.O.). Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid; CIBERNED (R.M.-F., R.R.-R., J.A.P.-P., I.O., C.G.-S., J.A.O.), Instituto Carlos III, Madrid; San Pablo-CEU University Medical School (R.M.-F., J.A.O.), Madrid, Spain. J.U.M.M. is currently at the Department of Neurology, IMED Hospitales, Valencia and the Universidad Autónoma de Madrid University-Instituto Cajal, Madrid, Spain.
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José Ángel Pineda-Pardo
From the HM CINAC (Centro Integral de Neurociencias Abarca Campal) (R.M.-F., E.N.-V., J.U.M.M., R.R.-R., M.D.A., J.A.P.-P., C.A., I.O., D.M.-M., F.H.-F., C.G.-S., M.M., F.A.-F., J.A.O.). Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid; CIBERNED (R.M.-F., R.R.-R., J.A.P.-P., I.O., C.G.-S., J.A.O.), Instituto Carlos III, Madrid; San Pablo-CEU University Medical School (R.M.-F., J.A.O.), Madrid, Spain. J.U.M.M. is currently at the Department of Neurology, IMED Hospitales, Valencia and the Universidad Autónoma de Madrid University-Instituto Cajal, Madrid, Spain.
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Claudia Ammann
From the HM CINAC (Centro Integral de Neurociencias Abarca Campal) (R.M.-F., E.N.-V., J.U.M.M., R.R.-R., M.D.A., J.A.P.-P., C.A., I.O., D.M.-M., F.H.-F., C.G.-S., M.M., F.A.-F., J.A.O.). Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid; CIBERNED (R.M.-F., R.R.-R., J.A.P.-P., I.O., C.G.-S., J.A.O.), Instituto Carlos III, Madrid; San Pablo-CEU University Medical School (R.M.-F., J.A.O.), Madrid, Spain. J.U.M.M. is currently at the Department of Neurology, IMED Hospitales, Valencia and the Universidad Autónoma de Madrid University-Instituto Cajal, Madrid, Spain.
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Ignacio Obeso
From the HM CINAC (Centro Integral de Neurociencias Abarca Campal) (R.M.-F., E.N.-V., J.U.M.M., R.R.-R., M.D.A., J.A.P.-P., C.A., I.O., D.M.-M., F.H.-F., C.G.-S., M.M., F.A.-F., J.A.O.). Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid; CIBERNED (R.M.-F., R.R.-R., J.A.P.-P., I.O., C.G.-S., J.A.O.), Instituto Carlos III, Madrid; San Pablo-CEU University Medical School (R.M.-F., J.A.O.), Madrid, Spain. J.U.M.M. is currently at the Department of Neurology, IMED Hospitales, Valencia and the Universidad Autónoma de Madrid University-Instituto Cajal, Madrid, Spain.
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David Mata-Marín
From the HM CINAC (Centro Integral de Neurociencias Abarca Campal) (R.M.-F., E.N.-V., J.U.M.M., R.R.-R., M.D.A., J.A.P.-P., C.A., I.O., D.M.-M., F.H.-F., C.G.-S., M.M., F.A.-F., J.A.O.). Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid; CIBERNED (R.M.-F., R.R.-R., J.A.P.-P., I.O., C.G.-S., J.A.O.), Instituto Carlos III, Madrid; San Pablo-CEU University Medical School (R.M.-F., J.A.O.), Madrid, Spain. J.U.M.M. is currently at the Department of Neurology, IMED Hospitales, Valencia and the Universidad Autónoma de Madrid University-Instituto Cajal, Madrid, Spain.
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Frida Hernández-Fernández
From the HM CINAC (Centro Integral de Neurociencias Abarca Campal) (R.M.-F., E.N.-V., J.U.M.M., R.R.-R., M.D.A., J.A.P.-P., C.A., I.O., D.M.-M., F.H.-F., C.G.-S., M.M., F.A.-F., J.A.O.). Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid; CIBERNED (R.M.-F., R.R.-R., J.A.P.-P., I.O., C.G.-S., J.A.O.), Instituto Carlos III, Madrid; San Pablo-CEU University Medical School (R.M.-F., J.A.O.), Madrid, Spain. J.U.M.M. is currently at the Department of Neurology, IMED Hospitales, Valencia and the Universidad Autónoma de Madrid University-Instituto Cajal, Madrid, Spain.
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Carmen Gasca-Salas
From the HM CINAC (Centro Integral de Neurociencias Abarca Campal) (R.M.-F., E.N.-V., J.U.M.M., R.R.-R., M.D.A., J.A.P.-P., C.A., I.O., D.M.-M., F.H.-F., C.G.-S., M.M., F.A.-F., J.A.O.). Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid; CIBERNED (R.M.-F., R.R.-R., J.A.P.-P., I.O., C.G.-S., J.A.O.), Instituto Carlos III, Madrid; San Pablo-CEU University Medical School (R.M.-F., J.A.O.), Madrid, Spain. J.U.M.M. is currently at the Department of Neurology, IMED Hospitales, Valencia and the Universidad Autónoma de Madrid University-Instituto Cajal, Madrid, Spain.
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Michele Matarazzo
From the HM CINAC (Centro Integral de Neurociencias Abarca Campal) (R.M.-F., E.N.-V., J.U.M.M., R.R.-R., M.D.A., J.A.P.-P., C.A., I.O., D.M.-M., F.H.-F., C.G.-S., M.M., F.A.-F., J.A.O.). Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid; CIBERNED (R.M.-F., R.R.-R., J.A.P.-P., I.O., C.G.-S., J.A.O.), Instituto Carlos III, Madrid; San Pablo-CEU University Medical School (R.M.-F., J.A.O.), Madrid, Spain. J.U.M.M. is currently at the Department of Neurology, IMED Hospitales, Valencia and the Universidad Autónoma de Madrid University-Instituto Cajal, Madrid, Spain.
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Fernando Alonso-Frech
From the HM CINAC (Centro Integral de Neurociencias Abarca Campal) (R.M.-F., E.N.-V., J.U.M.M., R.R.-R., M.D.A., J.A.P.-P., C.A., I.O., D.M.-M., F.H.-F., C.G.-S., M.M., F.A.-F., J.A.O.). Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid; CIBERNED (R.M.-F., R.R.-R., J.A.P.-P., I.O., C.G.-S., J.A.O.), Instituto Carlos III, Madrid; San Pablo-CEU University Medical School (R.M.-F., J.A.O.), Madrid, Spain. J.U.M.M. is currently at the Department of Neurology, IMED Hospitales, Valencia and the Universidad Autónoma de Madrid University-Instituto Cajal, Madrid, Spain.
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Jose A. Obeso
From the HM CINAC (Centro Integral de Neurociencias Abarca Campal) (R.M.-F., E.N.-V., J.U.M.M., R.R.-R., M.D.A., J.A.P.-P., C.A., I.O., D.M.-M., F.H.-F., C.G.-S., M.M., F.A.-F., J.A.O.). Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid; CIBERNED (R.M.-F., R.R.-R., J.A.P.-P., I.O., C.G.-S., J.A.O.), Instituto Carlos III, Madrid; San Pablo-CEU University Medical School (R.M.-F., J.A.O.), Madrid, Spain. J.U.M.M. is currently at the Department of Neurology, IMED Hospitales, Valencia and the Universidad Autónoma de Madrid University-Instituto Cajal, Madrid, Spain.
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Prospective Long-term Follow-up of Focused Ultrasound Unilateral Subthalamotomy for Parkinson Disease
Raúl Martínez-Fernández, Elena Natera-Villalba, Jorge U. Máñez Miró, Rafael Rodriguez-Rojas, Marta Marta del Álamo, José Ángel Pineda-Pardo, Claudia Ammann, Ignacio Obeso, David Mata-Marín, Frida Hernández-Fernández, Carmen Gasca-Salas, Michele Matarazzo, Fernando Alonso-Frech, Jose A. Obeso
Neurology Mar 2023, 100 (13) e1395-e1405; DOI: 10.1212/WNL.0000000000206771

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Abstract

Background and Objectives Unilateral magnetic resonance–guided focused ultrasound subthalamotomy (FUS-STN) has been shown to improve the cardinal motor features of Parkinson disease (PD). Whether this effect is sustained is not known. This study aims to report the long-term outcome of patients with PD treated with unilateral FUS-STN.

Methods We conducted a prospective open-label study of patients with asymmetrical PD who underwent unilateral FUS-STN. All patients were evaluated up to 36 months after treatment. The primary outcome was the difference from baseline to 36 months after FUS-STN in the score of the Movement Disorder Society–Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor part (III) for the treated hemibody in the off-medication state. The safety outcome included all adverse events occurring during follow-up. Secondary outcomes were the change in the MDS-UPDRS III score on-medication; subscores of rigidity, bradykinesia, tremor, and axial features; total MDS-UPDRS III; and the MDS-UPDRS part IV. Functional disability and quality of life were assessed using the MDS-UPDRS II and the PDQ39, respectively. Patient impression of change and satisfaction with the treatment were self-assessed. The Wilcoxon signed-rank test with subsequent Bonferroni's correction was used for data analysis.

Results Thirty-two patients with PD were evaluated at 36 months after treatment. The mean (±SD) age at baseline was 56.0 ± 10.1 years, with a mean disease duration of 6.8 ± 2.8 years. The MDS-UPDRS III score for the treated hemibody off-medication was improved by 52.3% from baseline to 3 years (score reduction from 19.0 ± 3.2 to 8.9 ± 3.3, 95% CI 8.7 to 11.6, p < 0.001), and all specific motor features were improved from baseline. No disabling or delayed adverse events were reported. The total MDS-UPDRS III off-medication score was 22.9% lower at 3 years than before treatment (36.8 ± 7.4 vs 27.4 ± 6.2, 95% CI 6.0 to 11.5, p < 0.001). The MDS-UPDRS II, IV, and PDQ39 scores and levodopa dose were equivalent to those at baseline.

Discussion The benefit of unilateral FUS-STN on PD motor features is sustained in the long term. FUS-STN contributes to better clinical control over several years of evolution. NCT02912871/03454425.

Classification of Evidence This study provides Class IV evidence on the utility of focused ultrasound unilateral subthalamotomy in the treatment of people with Parkinson disease.

Glossary

DBS=
deep brain stimulation;
ET=
essential tremor;
FUS-STN=
focused ultrasound subthalamotomy;
LEDD=
levodopa equivalent daily dose;
MDS-UPDRS=
Movement Disorder Society–Unified Parkinson's Disease Rating Scale;
PD=
Parkinson disease;
PDQ-39SI=
39-item Parkinson's Disease Questionnaire Summary Index;
STN=
subthalamic nucleus

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Submitted and externally peer reviewed. The handling editor was Associate Editor Peter Hedera, MD, PhD.

  • Editorial, page 601

  • Class of Evidence: NPub.org/coe

  • Received April 13, 2022.
  • Accepted in final form November 17, 2022.
  • © 2023 American Academy of Neurology
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