Metabolic Network Modulation by Bilateral Subthalamic Nucleus Stimulation in the Treatment of Advanced Parkinson's Disease

Introduction

Most patients suffering from Parkinson's disease (PD) in the advanced stage are poorly managed with medications alone. Neurosurgical interventions including lesioning and deep brain stimulation (DBS) provide effective choices but with the risk of adverse events mainly caused by the surgical procedure. DBS for PD was widely accepted in the late 1990s. Compared to other neurosurgical methods, DBS is attractive because of its adjustability and reversibility. Most DBS treatments target the subthalamic nucleus (STN) because the STN plays an important role in the modulation of the cortico-striato-pallido-thalamocortical (CSPTC) motor pathways in PD. The increasing activity of STN results in excessive inhibitory outflow from the basal ganglia to the thalamus and brain stem, which is associated with the motor symptoms in PD patients. By modulating the STN neural activity, the CSPTC pathway can be restored.

Abstract

Parkinson's disease (PD) in the advanced stage may require surgical interventions. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) was proposed to improve the symptoms of PD. Five patients (age 61.6±3.9 years) in advanced stage of PD were scanned using FDG-PET during both “ON” and “OFF” conditions of stimulation. Statistical parametric mapping (SPM) was used to assess the effect of the stimulation. Network analysis was also used to assess the effect of stimulation on the expression of an abnormal PD-related spatial covariance pattern (PDRP). Our study indicated that bilateral STN DBS increased the metabolism of the midbrain and decreased the metabolism of the parietal lobe, the cerebellum, lentiform nucleus, and the thalamus; it also reduced PDRP network activity that correlated significantly with the clinical improvement in advanced PD patients. All five patients who used levodopa as the only medication for PD reduced their daily dosage by approximately 30.7% (range 8.3–51.5%) after the surgery. These findings suggest that DBS is more likely to function by regulating the entire neuronetwork rather than merely exciting or inhibiting certain nucleus.

Keywords

PET, Parkinson's disease, deep brain stimulation