Deep brain stimulation of the Pedunculopontine nucleus and caudal Zona Incerta in patients with Parkinson’s disease

Axial symptoms including gait disturbance and postural instability are some of the most disabling symptoms of Parkinson's disease (PD) and in late stage disease these , symptoms can be resistant to both medical therapy and surgical intervention in the form of deep brain stimulation (DBS). In the on medication state axial symptoms show a limited response to deep brain stimulation of the conventional target sites. In this thesis I assess the effects of stimulating a novel target site, the Pedunculopontine nucleus (PPN) in isolation and in combination with stimulation in the subthalamic region / caudal Zona/ncerta (cZi) in patients with Parkinson's disease. At the time of commencing this work there were only two case reports describing the effects of deep brain stimulation of the PPN in isolation. An assessment is made of the safety and efficacy of the surgical technique. This has indicated that it is possible to accurately place a DBS electrode into the PPN with minimal peri-operative and post-operative complications. The efficacy data demonstrated a statistically significant improvement in the on medication axial symptoms, however it required dual site stimulation of both the PPN and cZI. PET scanning assessing regional cerebral blood flow (rCBF) demonstrated that stimulation of the PPN and cZi region induces changes in separate motor areas with each target. Concomitant PPN and cZi stimulation resulted in an additive effect on levels of rCBF, effectively combining the subcortical and cortical changes induced by stimulation of either target in isolation. Following analysis of the results from our initial case studies we are conducting a phase I/II safety and efficacy study, with a double blinded design and crossover between stimulation sites. Axial symptoms including gait disturbance and postural instability are some of the most disabling symptoms of Parkinson's disease (PO) and in late stage disease these I symptoms can be resistant to both medical therapy and surgical intervention in the form of deep brain stimulation (OBS). In the on medication state axial symptoms show a limited response to deep brain stimulation of the conventional target sites. In this thesis I assess the effects of stimulating a novel target site, the Pedunculopontine nucleus (PPN) in isolation and in combination with stimulation in the subthalamic region / caudal Zona Incerta (cZi) in patients with Parkinson's disease. At the time of commencing this work there were only two case reports describing the effects of deep brain stimulation of the PPN in isolation. An assessment is made of the safety and efficacy of the surgical technique. This has indicated that it is possible to accurately place a DBS electrode into the PPN with minimal peri-operative and post-operative complications. The efficacy data demonstrated a statistically significant improvement in the on medication axial symptoms, however it required dual site stimulation of both the PPN and cZl. PET scanning assessing regional cerebral blood flow (rCBF) demonstrated that stimulation of the PPN and cZi region induces changes in separate motor areas with each target. Concomitant PPN and cZi stimulation resulted in an additive effect on levels of rCBF, effectively combining the subcortical and cortical changes induced by stimulation of either target in isolation. Following analysis of the results from our initial case studies we are conducting a phase I/II safety and efficacy study, with a double blinded design and crossover between stimulation sites.