Pre-dopa Deep Brain Stimulation: Is Early Deep Brain Stimulation Able to Modify the Natural Course of Parkinson's Disease?

Abstract

Deep brain stimulation (DBS) is an established therapy for the management of Parkinson's disease (PD). However, DBS is indicated as the disease progresses and motor complications derived from pharmacological therapy arise. Here, we evaluate the potential of DBS prior to levodopa (L-Dopa) in improving quality of life (QoL), challenging the state of the art for DBS therapy. We present data on clinical manifestation, decision finding during early indication to DBS, and trajectories after DBS. We further discuss current paradigms for DBS and hypothesize on possible mechanisms. Six patients, between 50 and 67 years old, presenting at least 5 years of PD symptoms, and without L-Dopa therapy initiation, received subthalamic nucleus (STN) DBS implantation. In the six PD cases, indication for DBS was not driven by motor complications, as supported by current guidelines, but by relevant QoL impairment and patient's reluctance to initiate L-Dopa treatment. All patients treated with STN-DBS prior to L-Dopa presented improvement in motor and non-motor symptoms and significant QoL improvement. All patients reduced the intake of dopamine agonists, and five are currently free from L-Dopa medication, with no reported adverse events. We introduce a multicenter observational study to investigate whether early DBS treatment may affect the natural course of PD. Early application of DBS instead of L-Dopa administration could have a pathophysiological basis and be prompted by a significant incline on QoL through disease progression; however, the clinical value of this proposed paradigm shift should be addressed in clinical trials aimed at modulating the natural course of PD.

Keywords: Parkinson’s disease; deep brain stimulation; early deep brain stimulation; early intervention; subthalamic nucleus.

FIGURE 1

Unified Parkinson’s Disease Rating Scale Part III (UPDRS-III) scores before and at follow-up (3 months) after deep brain stimulation (DBS) surgery for each case reported and at a further proximal follow-up (6 months). (A) Motor scores in the medication OFF condition before DBS implantation and also stimulation OFF after DBS implantation. (B) Motor scores in the medication ON before DBS implantation, and medication OFF/stimulation ON condition after electrode implantation.

FIGURE 2

The 39-Item Parkinson’s Disease Questionnaire (PDQ-39) outcome scores of quality of life before and after deep brain stimulation (DBS) therapy (follow-up at 3 and 6 months) after DBS surgery for each case reported. Reduced PDQ-39 scores translate to an improvement in quality of life in Parkinson’s disease (PD) patients.