title: Pedunculopontine Nucleus Stimulation: Where are We Now and What Needs to be Done to Move the Field Forward?
abstract: Falls and gait impairment in Parkinson's Disease (PD) is a leading cause of morbidity and mortality, significantly impacting quality of life and contributing heavily to disability. Thus far axial symptoms, such as postural instability and gait freezing, have been refractory to current treatment approaches and remain a critical unmet need. There has been increased excitement surrounding the surgical targeting of the pedunculopontine nucleus (PPN) for addressing axial symptoms in PD. The PPN and cuneate nucleus comprise the mesencephalic locomotor region, and electrophysiologic studies in animal models and human imaging studies have revealed a key role for the PPN in gait and postural control, underscoring a potential role for DBS surgery. Previous limited studies of PPN deep brain stimulation (DBS) in treating gait symptoms have had mixed clinical outcomes, likely reflect targeting variability and the inherent challenges of targeting a small brainstem structure that is both anatomically and neurochemically heterogeneous. Diffusion tractography shows promise for more accurate targeting and standardization of results. Due to the limited experience with PPN DBS, several unresolved questions remain about targeting and programing. At present, it is unclear if there is incremental benefit with bilateral versus unilateral targeting of PPN or whether PPN targeting should be performed as an adjunct to one of the more traditional targets. The PPN also modulates non-motor functions including REM sleep, cognition, mood, attention, arousal, and these observations will require long-term monitoring to fully characterize potential side effects and benefits. Surgical targeting of the PPN is feasible and shows promise for addressing axial symptoms in PD but may require further refinements in targeting, improved imaging, and better lead design to fully realize benefits. This review summarizes the current knowledge of PPN as a DBS target and areas that need to be addressed to advance the field.
authors.affiliation: Department of Neurology, University of Florida Center for Movement Disorders and Neurorestoration , Gainesville, FL , USA.
authors.forename: Hokuto
authors.initials: H
authors.lastname: Morita
authors.affiliation: Department of Applied Physiology and Kinesiology, University of Florida , Gainesville, FL , USA.
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Hass
authors.affiliation: Department of Psychiatry and Neurology, CHU de Grenoble , Grenoble , France.
authors.forename: Elena
authors.initials: E
authors.lastname: Moro
authors.affiliation: Department of Radiation Oncology, University of California at San Francisco , San Francisco, CA , USA.
authors.forename: Atchar
authors.initials: A
authors.lastname: Sudhyadhom
authors.affiliation: Rocky Mountain Movement Disorder Center , Denver, CO , USA.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Department of Neurology, University of Florida Center for Movement Disorders and Neurorestoration , Gainesville, FL , USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Okun
keywords: Parkinson’s disease; deep brain stimulation; diffusion tractography; gait freezing; microelectrode recording; pedunculopontine nucleus; postural instability