Adaptive deep brain stimulation in patients with Parkinson’s disease: phase II clinical trial preliminary results

Abstract

Background: Emerging evidence now suggests that conventional deep brain stimulation (cDBS) for the treatment of Parkinson’s disease (PD) could be optimized using adaptive deep brain stimulation (aDBS) continuously supplies the stimulator with new settings obtained by analyzing control variable related to the patient’s current clinical state. A reliable control variable is subthalamic local field potential (LFP) activity recorded from the stimulating electrode itself.Objective: We designed a randomized, double-blind, cross-over clinical trial to compare the efficacy, the safety and the amount of charge delivered (TEED) of aDBS versus cDBS using an external dual (cDBS or aDBS) mode portable device controlled by LFPs.Patients and methods: Seven patients were randomly assigned to aDBS or cDBS as first treatment and blinded to the treatment. Both aDBS and cDBS were administered for 2 hours consecutively, during which the patient was assessed every 30 minutes, by a blinded investigator, through the UPDRS III and the Rush dyskinesia scales. The experimental sessions were also video-recorded in order to analyze any treatment related Adverse Events (AE).Results: Over the 2 hour of stimulation the patients exhibited a reduction of dyskinesias during aDBS compared to cDBS maintaining the same UPDRS III score. There were no treatment related AE (severe, moderate and mild) both during aDBS and cDBS. The TEED during aDBS was 70% less than cDBS (p < 0.03).Conclusions: Preliminary data showed that aDBS is safe and well tolerated in PD patients and decrease the amount of TEED, thus obtaining a reduction of dyskinesias. Our work should help understand how aDBS therapy works in PD and indicate future technical and clinical advances. Background: Emerging evidence now suggests that conventional deep brain stimulation (cDBS) for the treatment of Parkinson’s disease (PD) could be optimized using adaptive deep brain stimulation (aDBS) continuously supplies the stimulator with new settings obtained by analyzing control variable related to the patient’s current clinical state. A reliable control variable is subthalamic local field potential (LFP) activity recorded from the stimulating electrode itself. Objective: We designed a randomized, double-blind, cross-over clinical trial to compare the efficacy, the safety and the amount of charge delivered (TEED) of aDBS versus cDBS using an external dual (cDBS or aDBS) mode portable device controlled by LFPs. Patients and methods: Seven patients were randomly assigned to aDBS or cDBS as first treatment and blinded to the treatment. Both aDBS and cDBS were administered for 2 hours consecutively, during which the patient was assessed every 30 minutes, by a blinded investigator, through the UPDRS III and the Rush dyskinesia scales. The experimental sessions were also video-recorded in order to analyze any treatment related Adverse Events (AE). Results: Over the 2 hour of stimulation the patients exhibited a reduction of dyskinesias during aDBS compared to cDBS maintaining the same UPDRS III score. There were no treatment related AE (severe, moderate and mild) both during aDBS and cDBS. The TEED during aDBS was 70% less than cDBS (p < 0.03). Conclusions: Preliminary data showed that aDBS is safe and well tolerated in PD patients and decrease the amount of TEED, thus obtaining a reduction of dyskinesias. Our work should help understand how aDBS therapy works in PD and indicate future technical and clinical advances.