EPV004 - DIRECTIONAL VERSUS OMNIDIRECTIONAL DEEP BRAIN STIMULATION: RESULTS OF A MULTI‑CENTER PROSPECTIVE BLINDED CROSSOVER STUDY (ID 192)
- Jan Vesper, Germany
- Jan Vesper, Germany
- Pablo Mir, Spain
- Matthew Brodsky, United States of America
- Leonard Verhagen, United States of America
- Sergiu Groppa, Germany
- Ramiro Alvarez, Spain
- Andrew Evans, Australia
- Marta Blazquez, Spain
- Sean Nagels, United States of America
- Julie Pilitsis, United States of America
- Monika Pötter-Nerger, Germany
- Winona Tse, United States of America
- Leonardo Almeida, United States of America
- Nestor Tomycz, United States of America
- Joohi Jimenez-Shahed, United States of America
- Fatima Carrillo, Spain
- Christian J Hartmann, Germany
- Stefan Groiss, Germany
- Florence Defresne, Belgium
- Edward Karst, United States of America
- Binith Cheeran, United States of America
- Alfons Schnitzler, Germany
Abstract
Introduction
Published reports on directional DBS have been limited to small single-center investigations. Therapeutic window (TW) has been introduced in DBS to describe the range of stimulation amplitudes achieving symptom relief without side effects. The PROGRESS study evaluated whether directional DBS provides a wider TW in a large prospective trial.
Methods/Materials
Participants receiving subthalamic nucleus DBS for Parkinson’s disease were programmed with omnidirectional stimulation for 3 months, followed by directional stimulation for another 3 months. The subject was blinded to all details of stimulation, and a blinded evaluator assessed TW and motor symptoms. The primary endpoint was based on blinded off-medication evaluation of TW for directional vs. conventional stimulation at the 3-month follow-up. Additional endpoints at 3-, 6- and 12-month follow-ups included adverse events, subject and clinician stimulation preference, therapeutic current strength (TCS), quality of life and UPDRS part III motor score.
Results
A directional DBS system was implanted in 234 subjects (62±8 years, 33% female). No intracranial hemorrhages or infections occurred. At 3 months, TW was wider using directional stimulation in 90.6% of subjects, satisfying the primary endpoint for superiority (p<0.001). The mean increase in TW with directional stimulation was 41% (2.98±1.38mA, compared to 2.11±1.33mA for omnidirectional, p<0.001). The TCS was 39% lower with directional stimulation (1.11±1.00mA, compared to 1.83±1.52mA for omnidirectional, p<0.001). UPDRS part III motor score on medication was improved with either stimulation at each time point (p<0.001). After 6 months, 53% of subjects blinded to stimulation type (102/193) preferred the period with directional stimulation, 26% (50/193) preferred the omnidirectional period and 21% (41/193) had no preference. The directional period was preferred by 59% of clinicians (113/193) vs. 21% (41/193) who preferred the omnidirectional period.
Discussion
A double-blind randomized comparison of directional and omnidirectional stimulation found that 90.6% of subjects had a wider therapeutic window using directional stimulation. There were improvements in both the minimum amplitude required to achieve therapeutic benefit and the side effect threshold, leading to a 40% wider therapeutic window. Although results of the blinded motor examination did not differ significantly at 3 months after omnidirectional stimulation vs. 6 months after directional stimulation, there was improved Parkinson’s disease-specific quality of life. For the first time, we demonstrated superiority of directional programming in increasing therapeutic window compared to omnidirectional stimulation.
Conclusions
Directional stimulation yielded a wider TW compared to omnidirectional stimulation and was preferred by subjects blinded to stimulation type.
