Vestibulopathy, imbalance and gait disturbances in Parkinson disease

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The management of dopamine resistant postural instability and gait difficulty (PIGD) features, such as freezing of gait (FoG), represents perhaps the most important unmet clinical need in Parkinson's disease (PD). Research into the role of the vestibular system in the etiology of FoG has largely been neglected. Age- associated vestibular impairment (presbyvestibulopathy, PVP) is present in about half of older community- dwelling older persons and is a significant contributor to imbalance and falls. PVP is also common in PD, an age-related neurodegenerative disorder. We have novel preliminary data showing that PVP may be an important factor contributing to FoG. Confirmation of a mechanistic link between vestibular dysfunction and FoG has high clinical translational impact and may augur novel vestibular rehabilitation interventions, such as in-home portable thermoneuromodulation (TNM) to treat PD Veterans with otherwise treatment-refractory FoG. Plan: Our main aim will be a cross-sectional study in 64 Veterans with PD to investigate the relationship between PVP and FoG. Our exploratory aim will be a mechanistic feasibility trial of portable TNM in PD Veterans with FoG and PVP. Methods: We will perform detailed clinical, including dedicated motor and vestibular testing. PE2I dopamine transporter (DAT) PET will be used to assess the integrity of dopaminergic nigrostriatal innervation. Hypothesis 1: The prevalence of FoG is higher in Veterans with PD who also have evidence of PVP compared to those without PVP independent of nigrostriatal dopaminergic losses. Exploratory hypothesis: Active TNM stimulation will result in improved FoG severity ratings compared to sham stimulation in PD Veterans with FoG and PVP.