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Meta-Analysis
. 2025 Jan;32(1):e16524.
doi: 10.1111/ene.16524. Epub 2024 Oct 29.

Deep brain stimulation for severe dystonia associated with Wilson disease: A prospective multicenter meta-analysis of an N-of-1 trial

Chloé Laurencin  1   2   3 , Aurelia Poujois  4 , Maxime Bonjour  5   6   7 , Caroline Demily  8 , Hélène Klinger  1 , Emmanuel Roze  9   10 , Victoire Leclert  1 , Teodor Danaila  1 , Carole Langlois-Jacques  5   6   7 , Eduardo Couchonnal  3 , France Woimant  4 , Mickael Alexandre Obadia  4 , Gwennaelle Perez  4 , Michaela Pernon  4 , Laurianne Blanchet  1 , Emmanuel Broussolle  1 , Marie Vidailhet  9   10 , Behrouz Kassai  11 , Elena Moro  12 , Carine Karachi  13 , Gustavo Polo  14 , David Grabli  9   10 , Aurélie Portefaix  11 , Stéphane Thobois  1   2
Affiliations
Meta-Analysis

Deep brain stimulation for severe dystonia associated with Wilson disease: A prospective multicenter meta-analysis of an N-of-1 trial

Chloé Laurencin et al. Eur J Neurol. 2025 Jan.

Abstract

Background and purpose: Disabling dystonia despite optimal medical treatment is common in Wilson disease (WD). No controlled study has evaluated the effect of deep brain stimulation (DBS) on dystonia related to WD. This study was undertaken to evaluate the efficacy of DBS on dystonia related to WD.

Methods: A meta-analysis of an N-of-1 prospective, randomized, double-blind, multicenter DBS study was conducted at two French WD reference centers. Main inclusion criteria were patients with WD, stabilized for at least 6 months with significant disability due to dystonia despite optimized medical treatment. The subthalamic nucleus (STN) was targeted for bradykinetic patients with tonic dystonia, and the internal globus pallidus (GPi) was chosen for patients with hyperkinetic dystonia. Each patient underwent two periods of DBS "on" and two periods of DBS "off," each lasting 4 months. The order of stimulation conditions was randomized. The primary outcome was the change in the Canadian Occupational Performance Measure Performance (COPM-P) and Satisfaction scores after each 4-month period. Secondary outcomes were changes in the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) severity and disability scores and Unified Wilson's Disease Rating Scale (UWDRS) scores.

Results: Between 12 May 2016 and 7 October 2022, three patients were included. Two patients received bilateral GPi DBS, and one received bilateral STN DBS. There was no change of COPM-P (p = 0.956), BFMDRS, and UWDRS scores. No serious adverse events were reported.

Conclusions: STN or GPi DBS are ineffective on dystonia related to WD.

Keywords: Wilson disease; deep brain stimulation; dystonia.

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Conflict of interest statement

C.L.: Consulting fees from Orphalan, speaker's fee from Ellivie, travel grants from Abbvie and Adelia. A.Pou.: Research (institutional) grants from Orphalan, AddMedica, and Alexion; consulting fees from Orphalan, Univar, Alexion, and Vivet Therapeutics; speaker's fees from Alexion and Orphalan. C.D.: Meeting and travel grant from Orphalan. E.R.: Honoraria for speaking from Orkyn, Aguettant, Elivie, Merz‐Pharma, Teva, and Janssen and for participating on advisory boards from Merz‐Pharma, Elivie, Teva, and BIAL; travel grants from Elivie, Merz‐Pharma, Dystonia Medical Research Foundation, International Parkinson and Movement Disorders Society, and Brazilian Society for Child Neurology. He has received research support from Merz‐Pharma, Orkyn, Elivie, Everpharma, AMADYS, ADCY5.org, Dystonia Medical Research Foundation, Hope For Annabel, Cure Alternating Hemiplegia of Childhood, Alternating Hemiplegia of Childhood Foundation, Alternating Hemiplegia of Childhood Association of Iceland, Association française de l'hémiplégie alternante, and Alternating Hemiplegia of Childhood Kids of Netherlands. T.D.: Honorarium from Orkyn. E.M.: Honoraria from Medtronic for consultant services; grant support from Abbott, Grenoble Alpes University, and France Parkinson. C.K.: Personal fees from Boston Scientific and Medtronic for meetings and conferences. D.G.: Grants from AP‐HP (DRC‐PHRC) and France Parkinson; served on scientific advisory boards for AbbVie and Zambon; received research funding from Air Liquide and Orkyn; received speech honorarium from Medtronic, AbbVie, Merz, Orkyn, Aguettant, and EverPharma; received travel funding from AbbVie and Merz. S.T.: Honoraria from Boston, Medtronic, AbbVie, Merz, NHC, MDS for consulting, board membership, or conferences; meeting and travel grant from the MDS. None of the other authors has any conflict of interest to disclose.

Figures

FIGURE 1
FIGURE 1
Timeline of the research protocol.
FIGURE 2
FIGURE 2
Brain magnetic resonance imaging of the three patients (at the screening visit).
FIGURE 3
FIGURE 3
Unified Wilson Disease Rate Scale score evolution for the three patients.
See this image and copyright information in PMC

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