Efficacy of caudal pedunculopontine nucleus stimulation on postural instability and gait disorders in Parkinson's disease

Abstract

Objectives: Gait-related symptoms like postural instability and gait disorders (PIGD) inexorably worsen with Parkinson's disease (PD) deterioration and become refractory to current available medical treatment and deep brain stimulation (DBS) of conventional targets. Pedunculopontine nucleus (PPN) deep brain stimulation (DBS) is a promising method to treat PIGD. This prospective study aimed to clarify the clinical application of PPN-DBS and to explore effects of caudal PPN stimulation on PIGD.

Methods: Five consecutive PD patients with severe medication-resistant postural instability and gait disorders accepted caudal PPN-DBS. LEAD-DBS toolbox was used to reconstruct and visualize the electrodes based on pre- and postoperative images. Outcomes were assessed with Movement Disorder Society (MDS)-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS), gait-specific questionnaires, and objective gait analysis with GAITRite system.

Results: MDS-UPDRS subitems 35-38 scores were improved at postoperative 6 months (mean, 4.40 vs 11.00; p = 0.0006) and 12 months (mean, 5.60 vs 11.00; p = 0.0013) compared with baseline, and scores at 6 months were slightly lower than scores at 12 months (mean, 4.40 vs 5.60; p = 0.0116). Gait and Falls Questionnaire, New Freezing of Gait Questionnaire, and Falls Questionnaire scores also significantly improved at postoperative 6 months and 12 months compared with baseline. In addition, cadence, bilateral step length, and bilateral stride length significantly increased when PPN On-stimulation compared with Off-stimulation.

Conclusions: This study suggested that caudal PPN low-frequency stimulation improved PIGD for PD patients at the 6- and 12-month period.

Keywords: Deep brain stimulation; Gait; LEAD-DBS; Parkinson’s disease; Pedunculopontine nucleus.