Intraoperative changes in the H-reflex pathway during deep brain stimulation surgery for Parkinson's disease: A potential biomarker for optimal electrode placement

Abstract

Background: Deep Brain Stimulation (DBS) targeting the subthalamic nucleus (STN) and globus pallidus interna (GPi) is an effective treatment for cardinal motor symptoms and motor complications in Parkinson's Disease (PD). However, malpositioned DBS electrodes can result in suboptimal therapeutic response.

Objective: We explored whether recovery of the H-reflex-an easily measured electrophysiological analogue of the stretch reflex, known to be altered in PD-could serve as an adjunct biomarker of suboptimal versus optimal electrode position during STN- or GPi-DBS implantation.

Methods: Changes in soleus H-reflex recovery were investigated intraoperatively throughout awake DBS target refinement across 26 nuclei (14 STN). H-reflex recovery was evaluated during microelectrode recording (MER) and macrostimulation at multiple locations within and outside target nuclei, at varying stimulus intensities.

Results: Following MER, H-reflex recovery normalized (i.e., became less Parkinsonian) in 21/26 nuclei, and correlated with on-table motor improvement consistent with an insertional effect. During macrostimulation, H-reflex recovery was maximally normalized in 23/26 nuclei when current was applied at the location within the nucleus producing optimal motor benefit. At these optimal sites, H-reflex normalization was greatest at stimulation intensities generating maximum motor benefit free of stimulation-induced side effects, with subthreshold or suprathreshold intensities generating less dramatic normalization.

Conclusion: H-reflex recovery is modulated by stimulation of the STN or GPi in patients with PD and varies depending on the location and intensity of stimulation within the target nucleus. H-reflex recovery shows potential as an easily-measured, objective, patient-specific, adjunct biomarker of suboptimal versus optimal electrode position during DBS surgery for PD.

Keywords: Biomarker; Deep brain stimulation; Globus pallidus interna; H-reflex; Subthalamic nucleus.