Work

Deep brain stimulation in patients with mixed movement disorders linked to ADCY5

Year: 2025

Type: article

Abstract: INTRODUCTION: Pathogenic variants in ADCY5 cause mixed hyperkinetic movement disorders (MxMD-ADCY5) that can be occasionally refractory to medical treatment. While deep brain stimulation of the globus pallidus internus (GPi-DBS) has been previously used, knowledge on its indication, efficacy and safety is poor and mainly based on anecdotal reports and short case series. METHODS: We retrospectively reviewed clinical, genetic, therapeutic, and surgical data from patients with ADCY5-related movement disorders who underwent GPi-DBS, operated in two French expert centres or previously published. RESULTS: We obtained data from 23 patients for analysis. There were two distinct indications for GPi-DBS. The first group consisted of patients with long-standing, pharmacoresistant hyperkinetic movements. The second group included patients with acute motor exacerbations - fulfilling criteria for status dystonicus - and conceptually aligned with the recently proposed framework of severe acute motor exacerbation (SAME). Overall, GPi-DBS was safe and led to mild-to-moderate improvement of the motor condition in the two groups of patients. CONCLUSION: GPi-DBS can be considered as a relevant therapeutic option for MxMD-ADCY5 in case of pharmacological treatment failure both in patients with chronic motor impairment and those with paroxysmal exacerbations meeting criteria for SAME. Given the response to DBS in the two groups of patients, it is plausible that MxMD-ADCY5 reflects basal ganglia dysfunction mediated by dysregulated cAMP signalling, and that DBS acts by restoring homeostatic inhibitory control in these circuits.

Source: Revue Neurologique

DOI: 10.1016/j.neurol.2025.12.003