Emerging and Experimental Neurosurgical Treatments for Parkinson’s Disease

This chapter begins with a brief review of the neuropathology of Parkinson’s disease as it relates to emerging and experimental neurosurgical treatments. Initial emphasis is placed on existing models of basal ganglia circuits and their modulation by dopaminergic output from the substantia nigra pars compacta (SNc). Contemporary refinements in identifying the optimal anatomic targets for electrical stimulation in Parkinson’s disease are also discussed, together with advances in understanding the electrophysiologic and biochemical mechanisms underlying deep brain stimulation (DBS). The discussion then proceeds to review the principal emerging and experimental neurosurgical modalities being explored as treatments for Parkinson’s disease. These include advances in neurostimulation technology for DBS (adaptive “closed-loop” systems, directional “current steering” stimulation leads, and semi-automated device programming), image-guided ultrasound lesioning (MR-guided focused ultrasonography [MRgFUS]), transplantation of fetal neurons and more refined approaches involving transplantation of cells engineered using modern stem cell technology, as well as gene therapy techniques involving viral vectors, gene silencing, and gene editing technologies. Each therapeutic modality is addressed with attention both to scientific rationale and to clinical evidence, and results from major completed and ongoing human clinical trials are critically summarized.