Study Rationale:
Gait and balance disorders are the primary motor disability in advanced Parkinson’s disease (PD). These disorders arise in part due to dysfunction of the lateral mesencephalus [part of the brainstem] and one of its nuclei, the pedunculopontine nucleus (PPN). Deep brain stimulation (DBS) of the PPN area has been used to alleviate gait disorders, and while the initial clinical results were encouraging, the overall results are mixed.
Hypothesis:
This heterogeneity may be due to the variability between brainstem targets that have poorly defined boundaries, suggesting that DBS of the lateral mesencephalus may be effective but that we lack standardized tools for finding the ideal target.
Study Design:
In this project, we will construct a 3D deformable atlas for the human brainstem, as we have done previously for the human basal ganglia. We will test the efficacy of DBS of two different targets in the brainstem in 12 PD patients with resistant severe gait and balance disorders, in a randomized parallel cross-over double-blind study. We will make quantitative assessments using objective clinical and neurophysiological evaluations focused on gait and balance deficits.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
We hope that this study will produce new fundamental knowledge regarding the anatomy and the function of the brainstem in gait and balance control, in order to alleviate gait and balance disorders in people with PD.
Next Steps for Development:
We hope to identify the best target to improve gait and balance disorders in PD patients in order to propose this treatment in a larger cohort.
Trial Phase: IIB