Directional Deep Brain Stimulation for Parkinson's Disease: Results of an International Crossover Study With Randomized, Double-Blind Primary Endpoint
Alfons Schnitzler, Pablo Mir, Matthew Brodsky, L. Verhagen, Sergiu Groppa, Ramiro Álvarez, Andrew Evans, Marta Blázquez Estrada, Sean J. Nagel, Julie G. Pilitsis, Monika Pötter‐Nerger, Winona Tse, Leonardo Almeida, Nestor Tomycz, Joohi Jimenez‐Shahed, Witold Libionka, Fátima Carrillo, Christian J. Hartmann, Stefan Jun Groiss, Martin Gläser, Florence Defresne, Edward Karst, Binith Cheeran, Jan Vesper, Alfons Schnitzler, Jan Vesper, Pablo Mir, Leonardo Verhagen, Nestor Tomcyz, Christian J. Hartmann, Sergiu Groppa, Ramiro Álvarez, Julie G. Pilitsis, Monika Pötter‐Nerger, Stefan Jun Groiss, Matthew Brodsky
Abstract
OBJECTIVE: Published reports on directional deep brain stimulation (DBS) have been limited to small, single-center investigations. Therapeutic window (TW) is used to describe the range of stimulation amplitudes achieving symptom relief without side effects. This crossover study performed a randomized double-blind assessment of TW for directional and omnidirectional DBS in a large cohort of patients implanted with a DBS system in the subthalamic nucleus for Parkinson's disease. MATERIALS AND METHODS: Participants received omnidirectional stimulation for the first three months after initial study programming, followed by directional DBS for the following three months. The primary endpoint was a double-blind, randomized evaluation of TW for directional vs omnidirectional stimulation at three months after initial study programming. Additional data recorded at three- and six-month follow-ups included stimulation preference, therapeutic current strength, Unified Parkinson's Disease Rating Scale (UPDRS) part III motor score, and quality of life. RESULTS: The study enrolled 234 subjects (62 ± 8 years, 33% female). TW was wider using directional stimulation in 183 of 202 subjects (90.6%). The mean increase in TW with directional stimulation was 41% (2.98 ± 1.38 mA, compared to 2.11 ± 1.33 mA for omnidirectional). UPDRS part III motor score on medication improved 42.4% at three months (after three months of omnidirectional stimulation) and 43.3% at six months (after three months of directional stimulation) with stimulation on, compared to stimulation off. After six months, 52.8% of subjects blinded to stimulation type (102/193) preferred the period with directional stimulation, and 25.9% (50/193) preferred the omnidirectional period. The directional period was preferred by 58.5% of clinicians (113/193) vs 21.2% (41/193) who preferred the omnidirectional period. CONCLUSION: Directional stimulation yielded a wider TW compared to omnidirectional stimulation and was preferred by blinded subjects and clinicians.