Pallidal stimulation for Parkinson's disease

Abstract

There has been renewed interest in functional surgery as treatment for Parkinson's disease (PD). Although pallidotomy and chronic pallidal stimulation are highly effective in suppressing levodopa-induced dyskinesia (LID), both methods also seem to be effective in reducing parkinsonian disability. However, the simultaneous improvement of LID and motor signs is hard to explain with the classic model of basal ganglia circuitry. Taking advantage of the fact that deep brain stimulation is reversible and that implanted electrodes contain four discrete stimulation sites, we investigated the effect of stimulation on different sites of the globus pallidus (GP) in five PD patients. Stimulation in the dorsal GP (upper contact) significantly improved gait, akinesia, and rigidity and could induce dyskinesia when patients were in the "off" state. In contrast, stimulation in the posteroventral GP (lower contact) significantly worsened gait and akinesia, although the reduction in rigidity remained. For patients in the "on" state, stimulation in the posteroventral GP dramatically reduced LID but, as in the "off" state, worsened gait and akinesia, thus canceling out the antiparkinsonian effect of levodopa. Our results indicate that stimulation had a striking different effect on parkinsonism and dyskinesia when applied at two different loci of the GP and that stimulation applied in the posteroventral GP produced opposite effects on rigidity and on akinesia. We conclude that parkinsonian signs and LID are a reflection of at least two different anatomofunctional systems within the GP and that this functional organization of the GP needs to be considered when determining the optimal target for surgical treatment of PD.

Mechanisms and Targets of Deep Brain Stimulation in Movement Disorders

“…152 Three independent studies observed that monopolar HFS through electrode contacts in the ventral GPi significantly improved rigidity and levodopa-induced dyskinesias, and at times worsened bradykinesia. [153][154][155] On the other hand, stimulation of the proximal contacts putatively within the dorsal GPi led to improvement in bradykinesia and rigidity, but occasionally produced dyskinesias at higher voltages. These studies were unable to quantify the extent of current spread in each patient, making it unclear what cellular substrates were actually modulated for each stimulation paradigm.…”

Deep Brain Stimulation for Parkinson’s Disease

“…48 The complexity of the GPi might explain this variability of effect. 49,50 Some studies have reported an improvement in quality of life, largely related to the improvement in dyskinesias.…”

Controversial Issues in Deep Brain Stimulation in Parkinson's Disease

“…In fact, STN stimulation per se cannot ameliorate LID without decreasing dopaminergic medication [36]. Contrary to this, GPi stimulation may itself decrease the severity of LID [37]. The interaction between STN and GPi activity has been suggested to play a major role in the pathogenesis of dyskinesia, and the amelioration of stimulation-related dyskinesia through proximal contact (i.e., stimulating pallido-subthalamic fibers) shown in previous reports and our own young onset PD (YOPD) patients suggests a more beneficial effect of GPi than STN in ameliorating treatment-related dyskinesia.…”