Abstract

Introduction: Dysphagia is common in advanced Parkinson's disease (PD) leading to aspiration and pneumonia. These complications are relevant for quality of life of patients and increase morbidity and mortality. Standard treatment such as dopaminergic medication and deep brain stimulation of subthalamic nucleus (STN) often fall short to improve dysphagia. Stimulation of the substantia nigra pars reticulata (SNr) is of interest in dysphagia since experimental models suggested that SNr might be involved to swallowing. Here, we hypothesized that the combined stimulation of STN and SNr improves dysphagia compared with standard subthalamic nucleus stimulation at eight weeks of treatment. Patients and Methods: We enrolled PD patients with dysphagia. After a screening visit, the eligible patients entered an eight-week active treatment phase. Patients were assessed in “medication on” and “standard STN” at baseline (V1) and then were randomized 1:1 “standard STN” or “STN+SNr”. During the 8-week follow-up the participants received swallowing therapy as a standard care therapy in addition. After eight-weeks we evaluated swallowing function and clinical measures in a follow-up visit (V2). We focused on the oral and pharyngeal phase of swallowing. Our primary endpoint was the Penetration-Aspiration Scale (PAS). Additional to PAS, a visual analog scale (VAS) for pharyngeal residue in vallecular space and sinus piriformes and Site of Swallow Reflex Initiation (SOS) provided us further information about pharyngeal phase, penetration, and aspiration. We chose the “Test of Mastication and Swallowing Solids” (TOMASS) to study oral preparation and transport, SWAL-QoL scale for dysphagia-associated quality of life, and Functional oral intake scale (FOIS) for functional dimension. Results: We enrolled 20 patients. The PAS showed no significant difference in change from baseline between groups (P = 0.221). As secondary finding, we found that both patients from the STN and STN+SNr group showed better PAS at V2 compared to V1. VAS score for pharyngeal residue in sinus piriformes for solid food showed better outcome in “standard STN” group compared to “STN+SNr” group compared with baseline as well (P= 0.011). A difference of the number of swallows in the TOMASS score was found with lower number of swallows in the STN group (P = 0.025). Other outcome measures showed no difference between the groups. Conclusion: Our study did not show a superior effect of STN+SNr compared to STN. However, we found that the patients globally improved with dysphagia irrespective from the stimulation condition. This probably reflected the effect of continuous swallowing therapy and the increased patients‘ awareness towards swallowing. A closer pathophysiological understanding of the neuronal circuitry is therefore needed for specific neuromodulation intervention.

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