Author information

¹Department of Neurology C, Parkinson Expert Center, Pierre Wertheimer Neurological Hospital, Hospices Civils de Lyon, Bron, France.

²Lyon Neuroscience Research Center, INSERM U1028, CNRS UMR5292, PATH-PARK Team, University Lyon 1, Lyon, France.

³National Reference Center for Wilson Disease and Other Copper-Related Rare Diseases, Femme Mère Enfant Hospital, Hospices Civils de Lyon, Bron, France.

⁴National Reference Center for Wilson Disease and Other Copper-Related Rare Diseases, Neurology Department, Rothschild Foundation Hospital, Paris, France.

⁵Department of Biostatistics, Hospices Civils de Lyon, Lyon, France.

⁶Laboratoire de Biométrie et Biologie Évolutive, University Lyon 1, Villeurbanne, France.

⁷Faculté de Médecine Lyon Est, University Lyon 1, Lyon, France.

⁸Reference Center for Rare Diseases With Psychiatric Phenotype Génopsy, Le Vinatier Hospital, Bron, France.

⁹Sorbonne University, INSERM, CNRS, Paris, France.

¹⁰Brain Institute, Assistance Publique Hôpitaux de Paris, Salpêtrière Hospital, Paris, France.

¹¹Centre d'Investigation Clinique 1407, Hospices Civils de Lyon, Louis Pradel Hospital, Bron, France.

¹²Division of Neurology CHU Grenoble Alpes, Grenoble Institute of Neurosciences, INSERM U1216, Grenoble Alpes University, Grenoble, France.

¹³Neurosurgery Department, Hôpital de la Salpêtrière, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France.

¹⁴Neurosurgery Department A, Hospices Civils de Lyon, Pierre Wertheimer Neurological Hospital, Bron, France.

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.