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

What is the main crux?

The study titled ‘Deep brain stimulation for severe dystonia associated with Wilson disease: A prospective multicenter meta-analysis of an N of 1 trial’ published in January 2025 in the European Journal of Neurology investigated the efficacy of deep brain stimulation (DBS) for treating dystonia in patients with Wilson disease (WD). Conducted at multiple French WD reference centres, this prospective study included three patients with severe dystonia unresponsive to optimised medical management. 

Using an N of 1 trial design, each participant underwent two randomised "on" and two "off" DBS stimulation periods targeting either the subthalamic nucleus (STN) or the internal globus pallidus (GPi). Each phase lasted four months, and outcomes were assessed using the Canadian Occupational Performance Measure Performance (COPM-P) and Satisfaction scores, alongside secondary measures including the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and Unified Wilson's Disease Rating Scale (UWDRS). Despite rigorous trial conditions, the study reported no significant improvements in dystonia or quality of life across all measured parameters, indicating that DBS in its current form using this protocol was not an effective treatment for these three people with WD-related dystonia. Importantly, no serious adverse events were recorded during the trial.

What do we think about it?

This study has implications for both clinical practice and research on Wilson disease. For researchers, the study highlights the need to elucidate the pathophysiological mechanisms underlying dystonia in WD, which could inspire innovative neuromodulatory or pharmacological strategies. Medical device developers could gain insights into the limitations of this DBS system and protocol for WD, fostering innovation in modifying this system/protocol or designing other neuromodulation protocols. The study underscores the utility of N of 1 trial designs in rare disease research, providing a valuable methodological framework for personalised medicine and rare disease management.

Who are the Authors and where can I read the paper?

This study represents a significant collaborative effort, bringing together a diverse team of clinicians and researchers from multiple institutions across France and Europe. Leading experts such as Chloé Laurencin, Stéphane Thobois, and Marie Vidailhet are joined by neurologists, neurosurgeons, psychiatrists, and methodologists, including contributors like Behrouz Kassai and Carine Karachi, reflecting the interdisciplinary nature of the project. The study can be accessed here.