Bilateral deep brain stimulation of the pedunculopontine and subthalamic nuclei in severe Parkinson's disease

Abstract

Gait disturbances and akinesia are extremely disabling in advanced Parkinson's disease. It has been suggested that modulation of the activity of the pedunculopontine nucleus (PPN) may be beneficial in the treatment of these symptoms. We report the clinical affects of deep brain stimulation (DBS) in the PPN and subthalamic nucleus (STN). Six patients with unsatisfactory pharmacological control of axial signs such as gait and postural stability underwent bilateral implantation of DBS electrodes in the STN and PPN. Clinical effects were evaluated 2-6 months after surgery in the OFF- and ON-medication state, with both STN and PPN stimulation ON or OFF, or with only one target being stimulated. Bilateral PPN-DBS at 25 Hz in OFF-medication produced an immediate 45% amelioration of the motor Unified Parkinson's Disease Rating Scale (UPDRS) subscale score, followed by a decline to give a final improvement of 32% in the score after 3-6 months. In contrast, bilateral STN-DBS at 130-185 Hz led to about 54% improvement. PPN-DBS was particularly effective on gait and postural items. In ON-medication state, the association of STN and PPN-DBS provided a significant further improvement when compared to the specific benefit mediated by the activation of either single target. Moreover, the combined DBS of both targets promoted a substantial amelioration in the performance of daily living activities. These findings indicate that, in patients with advanced Parkinson's disease, PPN-DBS associated with standard STN-DBS may be useful in improving gait and in optimizing the dopamine-mediated ON-state, particularly in those whose response to STN only DBS has deteriorated over time. This combination of targets may also prove useful in extra-pyramidal disorders, such as progressive supranuclear palsy, for which treatments are currently elusive.

Mechanisms and Targets of Deep Brain Stimulation in Movement Disorders

“…DBS in the pedunculopontine nucleus (PPN), for example, is most effective at stimulation frequencies between 20 Hz and 60 Hz. 80 PPN neurons exhibit lower baseline firing rates (ϳ15 Hz on average) than those observed in other nuclei. 81,82 In dystonic cases, in which pathological GPi firing rates are thought to be lower than in PD, therapeutic DBS frequencies may also be lower.…”

“…1) (see also other reviews of DBS elsewhere in this issue [128][129][130][131] ). The primary targets of DBS for PD include the sensorimotor STN and GPi, 132 and recent studies suggest that the PPN, 80 GPe, 47 and motor cortex 133 are also effective targets. For most dystonias, the posteroventral GPi is now the preferred site of stimulation.…”

Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

“…Vim receives strong inputs from the cerebellum, and the effectiveness of tremor control with DBS at this location is a strong argument in favor of cerebellar involvement in the pathophysiology of tremor. PPN DBS [226][227][228][229][230][231][232][233][234][235][236][237][238][239], alone or in combination with STN or GPi DBS, is currently under study for patients with advanced PD who develop levodopaunresponsive freezing of gait, balance impairments, and falls. DBS of the PPN has been shown to be most effective at low stimulation frequencies [240].…”

Mechanisms of Deep Brain Stimulation in Movement Disorders as Revealed by Changes in Stimulus Frequency

“…Early findings suggest that DBS at 25 Hz in the pedunculopontine nucleus (PPN) improves gait in PD. 78 Case reports evaluating bilateral GPi DBS for HD yielded conflicting results during DBS at 40 Hz; chorea was improved in one subject, 79 but it was poorly controlled in another. 80 Finally, studies examining the effects of the frequency of GPi DBS for subjects with dystonia yielded heterogeneous results.…”