Deep brain stimulation for gait and postural disturbances in parkinson's disease

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by distal (i.e., tremor, bradykinesia, and rigidity) and axial motor symptoms (i.e., gait and postural disturbances). Deep brain stimulation (DBS) is a neurosurgical approach that uses electrical current delivered by an implantable pulse generator to modulate neural activity. Although DBS at the subthalamic nucleus (STN) and the internal globus pallidus (GPi) are well established for the treatment of the distal symptoms in PD, long-term studies of axial symptoms show a decline in efficacy with progression of the disease. Currently, there is no pharmacological or neurosurgical treatment available for the axial symptoms of advanced PD. Thus, the design of novel stimulation strategies to treat gait disturbances and postural instability has been investigated, including targets such as the pedunculopontine nucleus (PPN) and the substantia nigra pars reticulata (SNr). Here, we reviewed the current state of understanding regarding the effects of STN/GPi DBS, PPN DBS, and SNr DBS on gait and postural disturbances in PD and the proposed underlying mechanisms of action. The stimulation parameters (i.e., location, frequency, amplitude, and pulse width) and localization criteria for accurate placement of DBS electrodes within each target are discussed. As DBS at spatially distinct subregions of a target impacts the effectiveness of the therapy, electrode misplacement may directly contribute to the mixed results of DBS on the gait and postural disturbances of PD. We highlight the need for future studies to provide details on the specific subregion of the stimulation target to further advance the field.