Contribution of Basal Ganglia to the Sense of Upright: A Double-Blind Within-Person Randomized Trial of Subthalamic Stimulation in Parkinson’s Disease with Pisa Syndrome

Abstract

Background: Verticality perception is frequently altered in Parkinson’s disease (PD) with Pisa syndrome (PS). Is it the cause or the consequence of the PS? Objective: We tested the hypothesis that both scenarios coexist. Methods: We performed a double-blind within-person randomized trial (NCT02704910) in 18 individuals (median age 63.5 years) with PD evolving for a median of 17.5 years and PS for 2.5 years and treated with bilateral stimulation of the subthalamus nuclei (STN-DBS) for 6.5 years. We analyzed whether head and trunk orientations were congruent with the visual (VV) and postural (PV) vertical, and whether switching on one or both sides of the STN-DBS could modulate trunk orientation via verticality representation. Results: The tilted verticality perception could explain the PS in 6/18 (33%) patients, overall in three right-handers (17%) who showed net and congruent leftward trunk and PV tilts. Two of the 18 (11%) had an outstanding clinical picture associating leftward: predominant parkinsonian symptoms, whole-body tilt (head –11°, trunk –8°) and transmodal tilt in verticality perception (PV –10°, VV –8.9°). Trunk orientation or VV were not modulated by STN-DBS, whereas PV tilts were attenuated by unilateral or bilateral stimulations if it was applied on the opposite STN. Conclusion: In most cases of PS, verticality perception is altered by the body deformity. In some cases, PS seems secondary to a biased internal model of verticality, and DBS on the side of the most denervated STN attenuated PV tilts with a quasi-immediate effect. This is an interesting track for further clinical studies.