Related Experiment Video
Updated: Jun 30, 2026
Intra-Operative Behavioral Tasks in Awake Humans Undergoing Deep Brain Stimulation Surgery
Published on: January 6, 2011
Deep brain stimulation in patients with mixed movement disorders linked to ADCY5
E Retailleau1, N Dorison2, G Poulen3
1Inserm, CNRS, Hôpital Salpêtrière, Institut du Cerveau, Sorbonne Université, AP-HP, 75013 Paris, France.
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.
Insights
Globus pallidus internus deep brain stimulation (GPi-DBS) offers a safe treatment option for ADCY5-related movement disorders, improving both chronic and acute motor symptoms when medications fail.
Area of Science:
- Neuroscience
- Genetics
- Neurology
Background:
- Pathogenic variants in ADCY5 gene cause mixed hyperkinetic movement disorders (MxMD-ADCY5).
- These movement disorders can be refractory to medical treatments.
- Deep brain stimulation of the globus pallidus internus (GPi-DBS) has limited evidence for MxMD-ADCY5.
Purpose of the Study:
- To evaluate the indication, efficacy, and safety of GPi-DBS in patients with ADCY5-related movement disorders.
- To analyze patient data from French expert centers and published literature.
Main Methods:
- Retrospective review of clinical, genetic, therapeutic, and surgical data.
- Analysis included 23 patients with ADCY5-related movement disorders who underwent GPi-DBS.
- Patients were categorized into two groups based on GPi-DBS indication.
Main Results:
- Two main indications for GPi-DBS were identified: pharmacoresistant chronic hyperkinetic movements and acute motor exacerbations (status dystonicus/SAME).
- GPi-DBS demonstrated safety and resulted in mild-to-moderate motor improvement in both patient groups.
- Data from 23 patients were analyzed, combining data from two expert centers and published cases.
Conclusions:
- GPi-DBS is a viable therapeutic option for MxMD-ADCY5 when pharmacological treatments fail.
- The treatment is effective for both chronic motor impairment and paroxysmal exacerbations (SAME).
- DBS may restore inhibitory control in basal ganglia circuits, suggesting a role for cAMP signaling in MxMD-ADCY5 pathophysiology.
