Randomized Trial of Focused Ultrasound Subthalamotomy for Parkinson's Disease.

Adult Aged Double-Blind Method Dyskinesias / etiology Female Gait Disorders, Neurologic / etiology High-Intensity Focused Ultrasound Ablation / adverse effects Humans Male Middle Aged Motor Skills Parkinson Disease / physiopathology Postoperative Complications Severity of Illness Index Speech Disorders / etiology Subthalamic Nucleus / surgery

Journal

The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562

Informations de publication

Date de publication:
24 12 2020
Historique:
entrez: 28 12 2020
pubmed: 29 12 2020
medline: 15 1 2021
Statut: ppublish

Résumé

The subthalamic nucleus is the preferred neurosurgical target for deep-brain stimulation to treat cardinal motor features of Parkinson's disease. Focused ultrasound is an imaging-guided method for creating therapeutic lesions in deep-brain structures, including the subthalamic nucleus. We randomly assigned, in a 2:1 ratio, patients with markedly asymmetric Parkinson's disease who had motor signs not fully controlled by medication or who were ineligible for deep-brain stimulation surgery to undergo focused ultrasound subthalamotomy on the side opposite their main motor signs or a sham procedure. The primary efficacy outcome was the between-group difference in the change from baseline to 4 months in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor score (i.e., part III) for the more affected body side (range, 0 to 44, with higher scores indicating worse parkinsonism) in the off-medication state. The primary safety outcome (procedure-related complications) was assessed at 4 months. Among 40 enrolled patients, 27 were assigned to focused ultrasound subthalamotomy (active treatment) and 13 to the sham procedure (control). The mean MDS-UPDRS III score for the more affected side decreased from 19.9 at baseline to 9.9 at 4 months in the active-treatment group (least-squares mean difference, 9.8 points; 95% confidence interval [CI], 8.6 to 11.1) and from 18.7 to 17.1 in the control group (least-squares mean difference, 1.7 points; 95% CI, 0.0 to 3.5); the between-group difference was 8.1 points (95% CI, 6.0 to 10.3; P<0.001). Adverse events in the active-treatment group were dyskinesia in the off-medication state in 6 patients and in the on-medication state in 6, which persisted in 3 and 1, respectively, at 4 months; weakness on the treated side in 5 patients, which persisted in 2 at 4 months; speech disturbance in 15 patients, which persisted in 3 at 4 months; facial weakness in 3 patients, which persisted in 1 at 4 months; and gait disturbance in 13 patients, which persisted in 2 at 4 months. In 6 patients in the active-treatment group, some of these deficits were present at 12 months. Focused ultrasound subthalamotomy in one hemisphere improved motor features of Parkinson's disease in selected patients with asymmetric signs. Adverse events included speech and gait disturbances, weakness on the treated side, and dyskinesia. (Funded by Insightec and others; ClinicalTrials.gov number, NCT03454425.).

Sections du résumé

BACKGROUND
The subthalamic nucleus is the preferred neurosurgical target for deep-brain stimulation to treat cardinal motor features of Parkinson's disease. Focused ultrasound is an imaging-guided method for creating therapeutic lesions in deep-brain structures, including the subthalamic nucleus.
METHODS
We randomly assigned, in a 2:1 ratio, patients with markedly asymmetric Parkinson's disease who had motor signs not fully controlled by medication or who were ineligible for deep-brain stimulation surgery to undergo focused ultrasound subthalamotomy on the side opposite their main motor signs or a sham procedure. The primary efficacy outcome was the between-group difference in the change from baseline to 4 months in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor score (i.e., part III) for the more affected body side (range, 0 to 44, with higher scores indicating worse parkinsonism) in the off-medication state. The primary safety outcome (procedure-related complications) was assessed at 4 months.
RESULTS
Among 40 enrolled patients, 27 were assigned to focused ultrasound subthalamotomy (active treatment) and 13 to the sham procedure (control). The mean MDS-UPDRS III score for the more affected side decreased from 19.9 at baseline to 9.9 at 4 months in the active-treatment group (least-squares mean difference, 9.8 points; 95% confidence interval [CI], 8.6 to 11.1) and from 18.7 to 17.1 in the control group (least-squares mean difference, 1.7 points; 95% CI, 0.0 to 3.5); the between-group difference was 8.1 points (95% CI, 6.0 to 10.3; P<0.001). Adverse events in the active-treatment group were dyskinesia in the off-medication state in 6 patients and in the on-medication state in 6, which persisted in 3 and 1, respectively, at 4 months; weakness on the treated side in 5 patients, which persisted in 2 at 4 months; speech disturbance in 15 patients, which persisted in 3 at 4 months; facial weakness in 3 patients, which persisted in 1 at 4 months; and gait disturbance in 13 patients, which persisted in 2 at 4 months. In 6 patients in the active-treatment group, some of these deficits were present at 12 months.
CONCLUSIONS
Focused ultrasound subthalamotomy in one hemisphere improved motor features of Parkinson's disease in selected patients with asymmetric signs. Adverse events included speech and gait disturbances, weakness on the treated side, and dyskinesia. (Funded by Insightec and others; ClinicalTrials.gov number, NCT03454425.).

Identifiants

DOI: 10.1056/NEJMoa2016311 PMID: 33369354
pubmed: 33369354
doi: 10.1056/NEJMoa2016311
doi:

Banques de données

ClinicalTrials.gov
['NCT03454425']

Types de publication

Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2501-2513

Subventions

Organisme : University of Virginia
ID : Center of excellence grant
Pays : International

Commentaires et corrections

Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : CommentIn

Informations de copyright

Copyright © 2020 Massachusetts Medical Society.

Auteurs

Raúl Martínez-Fernández (R)

From HM Centro Integral en Neurociencias AC (CINAC), University Hospital HM Puerta del Sur, CEU San Pablo University, Mostoles (R.M.-F., J.U.M.-M., R.R.-R., M.A., F.H.-F., J.A.P.-P., M.H.G.M., B.F.-R., D.M.-M., P.G., F.A.-F., I.O., C.G.-S., L.V.-D., J.A.O.), and the Network Center for Biomedical Research on Neurodegenerative Diseases, Carlos III Institute, Madrid (R.M.-F., R.R.-R., M.A., F.H.-F., J.A.P.-P., D.M.-M., P.G., F.A.-F., I.O., C.G.-S., L.V.-D., J.A.O.) - both in Spain; and the University of Virginia Health Sciences Center, Charlottesville (B.B.S., S.A.S., W.J.E.).

Jorge U Máñez-Miró (JU)

From HM Centro Integral en Neurociencias AC (CINAC), University Hospital HM Puerta del Sur, CEU San Pablo University, Mostoles (R.M.-F., J.U.M.-M., R.R.-R., M.A., F.H.-F., J.A.P.-P., M.H.G.M., B.F.-R., D.M.-M., P.G., F.A.-F., I.O., C.G.-S., L.V.-D., J.A.O.), and the Network Center for Biomedical Research on Neurodegenerative Diseases, Carlos III Institute, Madrid (R.M.-F., R.R.-R., M.A., F.H.-F., J.A.P.-P., D.M.-M., P.G., F.A.-F., I.O., C.G.-S., L.V.-D., J.A.O.) - both in Spain; and the University of Virginia Health Sciences Center, Charlottesville (B.B.S., S.A.S., W.J.E.).

Rafael Rodríguez-Rojas (R)

From HM Centro Integral en Neurociencias AC (CINAC), University Hospital HM Puerta del Sur, CEU San Pablo University, Mostoles (R.M.-F., J.U.M.-M., R.R.-R., M.A., F.H.-F., J.A.P.-P., M.H.G.M., B.F.-R., D.M.-M., P.G., F.A.-F., I.O., C.G.-S., L.V.-D., J.A.O.), and the Network Center for Biomedical Research on Neurodegenerative Diseases, Carlos III Institute, Madrid (R.M.-F., R.R.-R., M.A., F.H.-F., J.A.P.-P., D.M.-M., P.G., F.A.-F., I.O., C.G.-S., L.V.-D., J.A.O.) - both in Spain; and the University of Virginia Health Sciences Center, Charlottesville (B.B.S., S.A.S., W.J.E.).

Marta Del Álamo (M)

From HM Centro Integral en Neurociencias AC (CINAC), University Hospital HM Puerta del Sur, CEU San Pablo University, Mostoles (R.M.-F., J.U.M.-M., R.R.-R., M.A., F.H.-F., J.A.P.-P., M.H.G.M., B.F.-R., D.M.-M., P.G., F.A.-F., I.O., C.G.-S., L.V.-D., J.A.O.), and the Network Center for Biomedical Research on Neurodegenerative Diseases, Carlos III Institute, Madrid (R.M.-F., R.R.-R., M.A., F.H.-F., J.A.P.-P., D.M.-M., P.G., F.A.-F., I.O., C.G.-S., L.V.-D., J.A.O.) - both in Spain; and the University of Virginia Health Sciences Center, Charlottesville (B.B.S., S.A.S., W.J.E.).

Binit B Shah (BB)

From HM Centro Integral en Neurociencias AC (CINAC), University Hospital HM Puerta del Sur, CEU San Pablo University, Mostoles (R.M.-F., J.U.M.-M., R.R.-R., M.A., F.H.-F., J.A.P.-P., M.H.G.M., B.F.-R., D.M.-M., P.G., F.A.-F., I.O., C.G.-S., L.V.-D., J.A.O.), and the Network Center for Biomedical Research on Neurodegenerative Diseases, Carlos III Institute, Madrid (R.M.-F., R.R.-R., M.A., F.H.-F., J.A.P.-P., D.M.-M., P.G., F.A.-F., I.O., C.G.-S., L.V.-D., J.A.O.) - both in Spain; and the University of Virginia Health Sciences Center, Charlottesville (B.B.S., S.A.S., W.J.E.).

Frida Hernández-Fernández (F)

From HM Centro Integral en Neurociencias AC (CINAC), University Hospital HM Puerta del Sur, CEU San Pablo University, Mostoles (R.M.-F., J.U.M.-M., R.R.-R., M.A., F.H.-F., J.A.P.-P., M.H.G.M., B.F.-R., D.M.-M., P.G., F.A.-F., I.O., C.G.-S., L.V.-D., J.A.O.), and the Network Center for Biomedical Research on Neurodegenerative Diseases, Carlos III Institute, Madrid (R.M.-F., R.R.-R., M.A., F.H.-F., J.A.P.-P., D.M.-M., P.G., F.A.-F., I.O., C.G.-S., L.V.-D., J.A.O.) - both in Spain; and the University of Virginia Health Sciences Center, Charlottesville (B.B.S., S.A.S., W.J.E.).

José A Pineda-Pardo (JA)

From HM Centro Integral en Neurociencias AC (CINAC), University Hospital HM Puerta del Sur, CEU San Pablo University, Mostoles (R.M.-F., J.U.M.-M., R.R.-R., M.A., F.H.-F., J.A.P.-P., M.H.G.M., B.F.-R., D.M.-M., P.G., F.A.-F., I.O., C.G.-S., L.V.-D., J.A.O.), and the Network Center for Biomedical Research on Neurodegenerative Diseases, Carlos III Institute, Madrid (R.M.-F., R.R.-R., M.A., F.H.-F., J.A.P.-P., D.M.-M., P.G., F.A.-F., I.O., C.G.-S., L.V.-D., J.A.O.) - both in Spain; and the University of Virginia Health Sciences Center, Charlottesville (B.B.S., S.A.S., W.J.E.).

Mariana H G Monje (MHG)

From HM Centro Integral en Neurociencias AC (CINAC), University Hospital HM Puerta del Sur, CEU San Pablo University, Mostoles (R.M.-F., J.U.M.-M., R.R.-R., M.A., F.H.-F., J.A.P.-P., M.H.G.M., B.F.-R., D.M.-M., P.G., F.A.-F., I.O., C.G.-S., L.V.-D., J.A.O.), and the Network Center for Biomedical Research on Neurodegenerative Diseases, Carlos III Institute, Madrid (R.M.-F., R.R.-R., M.A., F.H.-F., J.A.P.-P., D.M.-M., P.G., F.A.-F., I.O., C.G.-S., L.V.-D., J.A.O.) - both in Spain; and the University of Virginia Health Sciences Center, Charlottesville (B.B.S., S.A.S., W.J.E.).

Beatriz Fernández-Rodríguez (B)

From HM Centro Integral en Neurociencias AC (CINAC), University Hospital HM Puerta del Sur, CEU San Pablo University, Mostoles (R.M.-F., J.U.M.-M., R.R.-R., M.A., F.H.-F., J.A.P.-P., M.H.G.M., B.F.-R., D.M.-M., P.G., F.A.-F., I.O., C.G.-S., L.V.-D., J.A.O.), and the Network Center for Biomedical Research on Neurodegenerative Diseases, Carlos III Institute, Madrid (R.M.-F., R.R.-R., M.A., F.H.-F., J.A.P.-P., D.M.-M., P.G., F.A.-F., I.O., C.G.-S., L.V.-D., J.A.O.) - both in Spain; and the University of Virginia Health Sciences Center, Charlottesville (B.B.S., S.A.S., W.J.E.).

Scott A Sperling (SA)

From HM Centro Integral en Neurociencias AC (CINAC), University Hospital HM Puerta del Sur, CEU San Pablo University, Mostoles (R.M.-F., J.U.M.-M., R.R.-R., M.A., F.H.-F., J.A.P.-P., M.H.G.M., B.F.-R., D.M.-M., P.G., F.A.-F., I.O., C.G.-S., L.V.-D., J.A.O.), and the Network Center for Biomedical Research on Neurodegenerative Diseases, Carlos III Institute, Madrid (R.M.-F., R.R.-R., M.A., F.H.-F., J.A.P.-P., D.M.-M., P.G., F.A.-F., I.O., C.G.-S., L.V.-D., J.A.O.) - both in Spain; and the University of Virginia Health Sciences Center, Charlottesville (B.B.S., S.A.S., W.J.E.).

David Mata-Marín (D)

From HM Centro Integral en Neurociencias AC (CINAC), University Hospital HM Puerta del Sur, CEU San Pablo University, Mostoles (R.M.-F., J.U.M.-M., R.R.-R., M.A., F.H.-F., J.A.P.-P., M.H.G.M., B.F.-R., D.M.-M., P.G., F.A.-F., I.O., C.G.-S., L.V.-D., J.A.O.), and the Network Center for Biomedical Research on Neurodegenerative Diseases, Carlos III Institute, Madrid (R.M.-F., R.R.-R., M.A., F.H.-F., J.A.P.-P., D.M.-M., P.G., F.A.-F., I.O., C.G.-S., L.V.-D., J.A.O.) - both in Spain; and the University of Virginia Health Sciences Center, Charlottesville (B.B.S., S.A.S., W.J.E.).

Pasqualina Guida (P)

From HM Centro Integral en Neurociencias AC (CINAC), University Hospital HM Puerta del Sur, CEU San Pablo University, Mostoles (R.M.-F., J.U.M.-M., R.R.-R., M.A., F.H.-F., J.A.P.-P., M.H.G.M., B.F.-R., D.M.-M., P.G., F.A.-F., I.O., C.G.-S., L.V.-D., J.A.O.), and the Network Center for Biomedical Research on Neurodegenerative Diseases, Carlos III Institute, Madrid (R.M.-F., R.R.-R., M.A., F.H.-F., J.A.P.-P., D.M.-M., P.G., F.A.-F., I.O., C.G.-S., L.V.-D., J.A.O.) - both in Spain; and the University of Virginia Health Sciences Center, Charlottesville (B.B.S., S.A.S., W.J.E.).

Fernando Alonso-Frech (F)

From HM Centro Integral en Neurociencias AC (CINAC), University Hospital HM Puerta del Sur, CEU San Pablo University, Mostoles (R.M.-F., J.U.M.-M., R.R.-R., M.A., F.H.-F., J.A.P.-P., M.H.G.M., B.F.-R., D.M.-M., P.G., F.A.-F., I.O., C.G.-S., L.V.-D., J.A.O.), and the Network Center for Biomedical Research on Neurodegenerative Diseases, Carlos III Institute, Madrid (R.M.-F., R.R.-R., M.A., F.H.-F., J.A.P.-P., D.M.-M., P.G., F.A.-F., I.O., C.G.-S., L.V.-D., J.A.O.) - both in Spain; and the University of Virginia Health Sciences Center, Charlottesville (B.B.S., S.A.S., W.J.E.).

Ignacio Obeso (I)

From HM Centro Integral en Neurociencias AC (CINAC), University Hospital HM Puerta del Sur, CEU San Pablo University, Mostoles (R.M.-F., J.U.M.-M., R.R.-R., M.A., F.H.-F., J.A.P.-P., M.H.G.M., B.F.-R., D.M.-M., P.G., F.A.-F., I.O., C.G.-S., L.V.-D., J.A.O.), and the Network Center for Biomedical Research on Neurodegenerative Diseases, Carlos III Institute, Madrid (R.M.-F., R.R.-R., M.A., F.H.-F., J.A.P.-P., D.M.-M., P.G., F.A.-F., I.O., C.G.-S., L.V.-D., J.A.O.) - both in Spain; and the University of Virginia Health Sciences Center, Charlottesville (B.B.S., S.A.S., W.J.E.).

Carmen Gasca-Salas (C)

From HM Centro Integral en Neurociencias AC (CINAC), University Hospital HM Puerta del Sur, CEU San Pablo University, Mostoles (R.M.-F., J.U.M.-M., R.R.-R., M.A., F.H.-F., J.A.P.-P., M.H.G.M., B.F.-R., D.M.-M., P.G., F.A.-F., I.O., C.G.-S., L.V.-D., J.A.O.), and the Network Center for Biomedical Research on Neurodegenerative Diseases, Carlos III Institute, Madrid (R.M.-F., R.R.-R., M.A., F.H.-F., J.A.P.-P., D.M.-M., P.G., F.A.-F., I.O., C.G.-S., L.V.-D., J.A.O.) - both in Spain; and the University of Virginia Health Sciences Center, Charlottesville (B.B.S., S.A.S., W.J.E.).

Lydia Vela-Desojo (L)

From HM Centro Integral en Neurociencias AC (CINAC), University Hospital HM Puerta del Sur, CEU San Pablo University, Mostoles (R.M.-F., J.U.M.-M., R.R.-R., M.A., F.H.-F., J.A.P.-P., M.H.G.M., B.F.-R., D.M.-M., P.G., F.A.-F., I.O., C.G.-S., L.V.-D., J.A.O.), and the Network Center for Biomedical Research on Neurodegenerative Diseases, Carlos III Institute, Madrid (R.M.-F., R.R.-R., M.A., F.H.-F., J.A.P.-P., D.M.-M., P.G., F.A.-F., I.O., C.G.-S., L.V.-D., J.A.O.) - both in Spain; and the University of Virginia Health Sciences Center, Charlottesville (B.B.S., S.A.S., W.J.E.).

W Jeffrey Elias (WJ)

From HM Centro Integral en Neurociencias AC (CINAC), University Hospital HM Puerta del Sur, CEU San Pablo University, Mostoles (R.M.-F., J.U.M.-M., R.R.-R., M.A., F.H.-F., J.A.P.-P., M.H.G.M., B.F.-R., D.M.-M., P.G., F.A.-F., I.O., C.G.-S., L.V.-D., J.A.O.), and the Network Center for Biomedical Research on Neurodegenerative Diseases, Carlos III Institute, Madrid (R.M.-F., R.R.-R., M.A., F.H.-F., J.A.P.-P., D.M.-M., P.G., F.A.-F., I.O., C.G.-S., L.V.-D., J.A.O.) - both in Spain; and the University of Virginia Health Sciences Center, Charlottesville (B.B.S., S.A.S., W.J.E.).

José A Obeso (JA)

From HM Centro Integral en Neurociencias AC (CINAC), University Hospital HM Puerta del Sur, CEU San Pablo University, Mostoles (R.M.-F., J.U.M.-M., R.R.-R., M.A., F.H.-F., J.A.P.-P., M.H.G.M., B.F.-R., D.M.-M., P.G., F.A.-F., I.O., C.G.-S., L.V.-D., J.A.O.), and the Network Center for Biomedical Research on Neurodegenerative Diseases, Carlos III Institute, Madrid (R.M.-F., R.R.-R., M.A., F.H.-F., J.A.P.-P., D.M.-M., P.G., F.A.-F., I.O., C.G.-S., L.V.-D., J.A.O.) - both in Spain; and the University of Virginia Health Sciences Center, Charlottesville (B.B.S., S.A.S., W.J.E.).

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Randomized Trial of Focused Ultrasound...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Randomized Trial of Focused Ultrasound...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Méthodologie en recherche épidémiologique › Méthode en double aveugle › Randomized Trial of Focused Ultrasound...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Manifestations neurologiques › Dyskinésies › Randomized Trial of Focused Ultrasound...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Manifestations neurologiques › Troubles neurologiques de la marche › Randomized Trial of Focused Ultrasound...
questionsmedicales.fr › Procédures de chirurgie opératoire › Techniques d'ablation › Ablation par ultrasons focalisés de haute intensité › Randomized Trial of Focused Ultrasound...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Randomized Trial of Focused Ultrasound...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Randomized Trial of Focused Ultrasound...
questionsmedicales.fr › Phénomènes psychologiques › Aptitudes motrices › Randomized Trial of Focused Ultrasound...
questionsmedicales.fr › Maladies du système nerveux › Maladies neurodégénératives › Maladie de Parkinson › Randomized Trial of Focused Ultrasound...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Complications postopératoires › Randomized Trial of Focused Ultrasound...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Collecte de données › Enquêtes et questionnaires › Enquêtes de santé › Indicateurs d'état de santé › Acuité des besoins du patient › Indice de gravité de la maladie › Randomized Trial of Focused Ultrasound...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Manifestations neurologiques › Troubles du langage › Troubles de la parole › Randomized Trial of Focused Ultrasound...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Prosencéphale › Diencéphale › Subthalamus › Noyau subthalamique › Randomized Trial of Focused Ultrasound...