Combined stimulation of the substantia nigra pars reticulata and the subthalamic nucleus is effective in hypokinetic gait disturbance in Parkinson’s disease

Abstract

Severe gait disturbances in idiopathic Parkinson’s disease (PD) are observed in up to 80% of all patients in advanced disease stages [1, 2] with an important impact on quality of life [3–5]. While segmental symptoms generally respond well to dopaminergic medication and high-frequent deep brain stimulation of the subthalamic nucleus (STN-DBS), treatment of gait disturbances often remains unsatisfactory [5–7]. DBS of the pedunculopontine area is currently under investigation to treat gait disturbances and imbalance in PD; however, appropriate targeting and patient selection remain controversial [8–10]. Here, we describe a novel stimulation paradigm of simultaneous stimulation on distant electrode contacts located in the STN and the caudal border zone between the STN and substantia nigra pars reticulata (SNr) in a patient with a severe hypokinetic gait disturbance. A 72-year-old female patient with PD (Hoehn & Yahr IV, disease duration 20 years) with severe dopaminergic motor fluctuations including wearing off, peak-dose dyskinesias since 2007, and severe hypokinetic gait disturbance was referred to our center for deep brain stimulation and, therefore, considered for STN-DBS. A quadripolar electrode (type 3389, Medtronic, Minneapolis, MN, USA) was inserted into each STN and connected to an implantable pulse stimulator (Activa PC, Medtronic, Minneapolis, MN, USA). Localizations of the active electrode contacts were determined from the postoperative MR imaging and co-registration between preand postoperative imaging. Stimulation pulses can be delivered more selectively on distant contacts of a lead using a novel paradigm of the socalled ‘interleaved pulses’, i.e., impulses are delivered simultaneously on two different contacts in alternating order (e.g., 125 Hz on each contact). Importantly, each of the contacts can be programmed with specific parameters (e.g., amplitude, pulse width). Short-term effects of three different stimulator settings on a timed walking test [11] were tested 6 months after DBS surgery after 30 minutes of constant settings: (1) stimulation off [StimOff], (2) conventional stimulation on proximal STN contacts [STNmono], and (3) combined [STN ? SNr] using interleaving pulses on contacts located in both the STN area and the caudal border zone of STN and SNr (detailed parameters in Table 1). Dopaminergic medications were withdrawn overnight. In order to limit the patient’s knowledge of the current stimulator settings, DBS was switched on and off several times before the final parameters were maintained. Further follow-up examinations on both [STNmono] and [STN ? SNr] were performed after 2 weeks of constant stimulation on either setting. The freezing of gait questionnaire (FOG-Q) [12], PD-Q 39, and axial UPDRS subscores (UPDRS II, items 13–15 and Electronic supplementary material The online version of this article (doi:10.1007/s00415-011-5906-3) contains supplementary material, which is available to authorized users.