Vestibular Function in People with Parkinson Disease and the Effects of Dopaminergic Medication

Abstract

There is growing evidence suggesting that Parkinson disease (PD) affects the vestibular system, which senses head accelerations including gravity. People with PD report symptoms consistent with vestibular dysfunction that may begin prior to their PD diagnosis. Vestibular dysfunction may also contribute to postural instability which is common with disease progression. In addition to the otolithic and semicircular canal (SCC) end organs in the periphery, the vestibular system has broad sub-cortical and cortical connectivity leading to multiple potential routes for PD pathology to affect vestibular function. However, it is unclear if vestibular dysfunction in PD is disease-specific, age-related, or both. Furthermore, it is unknown how dopaminergic medications used to treat PD may affect vestibular function. Due to the distributed nature of vestibular connections and the inability to record from the end organs directly, localization of vestibular pathology in humans requires a comprehensive examination. The overarching objective of this dissertation is to understand how Parkinson disease and dopaminergic medications used to treat PD affect peripheral and central vestibular function in people with PD. This objective was met through the completion of two projects: a retrospective review of vestibular test records, and a prospective comparison of comprehensive vestibular testing in healthy controls and participants with PD, off-medication and on-medication.First, a retrospective records review was performed to examine the results of comprehensive vestibular testing completed by people with PD at the University of Washington Dizziness and Balance Center. The record review aimed to characterize vestibular function in people with PD referred for vestibular testing compared to adults without PD who also completed testing at the center. It was hypothesized based on prior literature that vestibular test results would show specifically otolithic dysfunction in the periphery and a pattern of central vestibular involvement across disease stages. Records that included a diagnosis of PD were categorized based on the timing of the PD diagnosis relative to the date of vestibular testing as prodromal (vestibular assessment before PD diagnosis) or clinical (vestibular assessment within one year of or any time after PD diagnosis). Age and gender matching of PD records to non-PD control group (CG) records at a 1:2 ratio was then performed. The primary comparison was to determine if there were significant differences in vestibular test results between PD and CG, based on the presence of a diagnosis of PD. Secondary comparisons determined if there were differences based on disease severity. Comparisons were made for CG and prodromal PD, CG and clinical PD, and between the two PD groups. Results were partially aligned with the expected outcome. Unlike expectations, there were no differences between CG and PD records for otolithic function. Consistent with expectations, central signs were present for the PD groups suggesting vestibulo-cerebellar dysfunction in all 3 three comparisons where sufficient data was available. All groups showed poor postural control performance. These findings suggest that peripheral otolithic dysfunction may not be more prevalent in PD than in typical aging, but central vestibular dysfunction that includes the cerebellum may be present in PD even at early disease stages. Second, a prospective study used comprehensive vestibular testing to determine if vestibular function in PD is different from healthy older adults and to examine the effects of dopaminergic medication on vestibular function in PD. For the first aim, it was anticipated that, compared to healthy controls (HC), people with PD would have abnormalities in otolithic function, vestibular nucleus complex (VNC) functions, and vestibular sensory integration. For the second aim, it was anticipated that dopaminergic medication would improve otolithic function and inhibit central functions. To test this, 15 HC and 15 participants with PD completed comprehensive vestibular testing. Participants with PD completed testing when functionally off their dopaminergic medications for PD (OFF), and while on-medication (ON). Both aims used the same primary variables representing otolithic function, SCC function, VNC function, and vestibular sensory integration for postural control. Secondary variables were also collected and compared to provide context to interpret primary test results. To test for PD-specific vestibular deficits without any potential medication effects, vestibular test results for participants with PD, OFF, were compared to HC. It was expected that otolithic function would be abnormal in PD, however, the comparison found that otolithic function in PD was not significantly different from HC. Instead, there was evidence for reduced SCC function. The primary central function variables were not significantly different in PD. However, for secondary variables, there were significant signs of dysfunction of the VNC and cerebellum, abnormal visual verticality perception, and well-known saccadic eye movement abnormalities. The second aim of the prospective project, to determine the effects of dopaminergic medication on vestibular function in PD, used a quasi-experimental design. The results of participants with PD, OFF, were compared to ON. It was anticipated that medication would improve otolithic function and impair central vestibular functions. The results of comparisons showed no effect of medication on either peripheral or central vestibular function. However, there was a high prevalence of abnormal test results both OFF and ON. These findings indicate that there may be disease-specific VNC, cerebellar, and cortical vestibular processing abnormalities in PD affecting non-dopaminergic pathways. In conclusion, the work of this dissertation demonstrates that disease-related central vestibular dysfunction may exist in people with PD, potentially at early disease stages. Additionally, the evidence that vestibular dysfunction in PD is not responsive to dopaminergic medications indicates potential non-dopaminergic pathway involvement in PD. Further research is needed to determine if this vestibular dysfunction is related to postural control and gait deficits, or non-motor symptoms in PD. Finally, examination and individualized treatment using established vestibular rehabilitation techniques and the development of novel interventions targeting vestibular function should be considered for people with PD.