Deep Brain Stimulation of the Pedunculopontine Tegmental Nucleus Improves Static Balance in Parkinson’s Disease

Introduction

Postural instability is a severe symptom in Parkinson’s disease (PD) and atypical Parkinsonisms that causes falls and postural deformities ( ). The treatment of postural instability in PD with antiParkinsonian drugs is unsatisfactory, and frequent falls occur in patients who experience good pharmacological control of other motor disabilities ( ).

The origin of this postural instability that leads to falling is unclear. It has been hypothesized that postural instability in PD patients may result from dysfunctions of processing and integration of sensory signals and deficits in motor adjustment processes and muscle tone regulation. Correct sensory processing requires the integration of visual, vestibular, and somatosensory signals, so that motor adjustments can be executed in the presence of proper basic muscle tone. In normal subjects control mechanisms occur in a normal fashion, and visual cues play an essential role in overall balance control. In contrast, in PD patients one or all of these control systems is affected ( ), and balance becomes highly dependent on visual cues.

Deep brain stimulation (DBS) of basal ganglia nuclei has been applied in an attempt to improve postural instability in l -dopa-resistant PD and other Parkinsonian syndromes. The subthalamic nucleus (STN) and globus pallidus internus (GPi) have been the most common targets for DBS ( ) in an attempt to improve postural control in PD. The results of these and other related studies were the object of a recent comprehensive review ( ). In brief, unsatisfactory results for STN DBS and GPi DBS on balance disorders have been reported in PD patients, and even aggravation of imbalance has been observed in some patients. Also, a combination of l -dopa with DBS has yielded unsatisfactory results, in particular when medication has been used with STN DBS.

In the last decade, in patients with PD who were poorly responsive to pharmacological and/or surgical therapies, the pedunculopontine tegmental nucleus (PPTg) has emerged as a promising DBS target ( ). Besides the fact that stimulation of this structure has been found to elicit locomotion in animals, interest in the PPTg has been raised by the possibility that it may serve as a basal ganglia output to motor spinal cord mechanisms, bypassing both the thalamocortical route and dopaminergic nigrostriatal mechanisms ( ), and facilitating arousal and reward mechanisms that might increase patient attention in the production of voluntary movements ( ). In addition, it has been shown that PPTg DBS may modulate somatosensory evoked potentials, suggesting that it could also affect integration and processing of sensory signals ( ).

The relatively low number of PPTg DBS patients does not allow one to draw definitive conclusions concerning the role of PPTg in motor control, but improvement of freezing of gait and a reduction of falls have been consistently reported, despite some inconsistencies in gait parameters that are likely due to patient selection, stage of disease, and precise site of stimulation. In a previous study ( ) we reported that PPTg DBS improved gait initiation and specific spatio–temporal and kinematic parameters during unconstrained walking, suggesting that the improved gait initiation may help overcome the block of preparation for movement that is present in gait freezing.

Given these premises, the aim of our study was to assess the effects of unilateral PPTg stimulation on postural balance in patients who were previously subjected to gait analysis ( ). Postural balance was assessed by evaluating fluctuations in the center of pressure (CoP) during upright stance. We used the CoP to assess postural balance because it represents a reliable index of the point location of the ground reaction force vector, reflecting the sway of the body and the forces used to maintain the center of gravity within the support base.

Methods and Materials