New Targets and New Technologies in the Treatment of Parkinson's Disease: A Narrative Review

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disease, whose main neuropathological finding is pars compacta degeneration due to the accumulation of Lewy bodies and Lewy neurites, and subsequent dopamine depletion. This leads to an increase in the activity of the subthalamic nucleus (STN) and the internal globus pallidus (GPi). Understanding functional anatomy is the key to understanding and developing new targets and new technologies that could potentially improve motor and non-motor symptoms in PD. Currently, the classical targets are insufficient to improve the entire wide spectrum of symptoms in PD (especially non-dopaminergic ones) and none are free of the side effects which are not only associated with the procedure, but with the targets themselves. The objective of this narrative review is to show new targets in DBS surgery as well as new technologies that are under study and have shown promising results to date. The aim is to give an overview of these new targets, as well as their limitations, and describe the current studies in this research field in order to review ongoing research that will probably become effective and routine treatments for PD in the near future.

Keywords: Parkinson’s disease; deep brain stimulation; functional neuroanatomy; neurosurgery; new targets; new technologies; subthalamic nucleus.

Figure 1

This figure shows a coronal section of the basal ganglia circuit with emphasis on its complex connections. Illustrated by J. Lizana.

Figure 2

Figure (a) depicts the classical pallidofugal pathways, while Figure (b) illustrates some changes in the recent understanding of how the Globus pallidus communicates with other basal ganglia structures. Illustrated by J. Lizana.

Figure 3

A sagittal section of the brain, trunk and cerebellum shows the complex connections between basal ganglia and cerebellum. AMY, Amygdala; BC, Brain cortex; CC, Cerebellar cortex; CiC, Cingulate cortex; CN, Caudate nucleus; DN, Dentate nucleus; FN, Fastigial nucleus; GPe, External globus pallidus; GPi, Internal globus pallidus; IN, Interpositus nucleus; NAcc, Nucleus accumbens; NBM, Nucleus basalis of Meynert; PN, Pontine nuclei; PUT, Putamen; RN, Red nucleus; STH, Subthalamus; THA, Thalamus. Illustrated by J. Lizana.

Figure 4

This figure shows some theoretical locations (superior sagittal sinus, internal cerebral vein and basal vein of Rosenthal) of STENTrodes which can be placed by the endovascular transvenous approach to stimulate the cortex, thalamus or brainstem nuclei. Illustrated by J. Lizana.