Dopaminergic nerve terminal, medication status, and vestibular function testing in Parkinson’s Disease

Introduction: The vestibular system plays a key role in postural stability as it acts to orient one's head position and movements in space. Impaired postural stability is a well-documented symptom of Parkinson's disease (PD). Evidence of vestibular dysfunction has been noted in PD and may play a role in the impaired postural stability and poor balance seen in this population. The loss of dopaminergic neurons is also a hallmark sign of PD. However, little is known about the role of dopamine in vestibular dysfunction. Furthermore, it is unknown if dopaminergic medications affect vestibular testing outcomes in PD despite the fact that extra-ocular muscles may be similarly affected by PD as other striatal skeletal muscles. We hypothesized that bradykinesia-dependent measures (i.e., velocity of smooth pursuit) may be altered by dopaminergic medications (i.e., faster velocity while on medications).

Methods: Eight subjects with PD (male; mean age 70.1, SD=4.0 years; mean Hoehn Yahr stage 2.1, SD= 0.4) underwent vestibular testing both on and off their dopaminergic medications. The vestibular testing battery included assessments of vestibulo-ocular reflex (VOR) gain and nystagmus using the video head impulse test (vHIT), sinusoidal harmonic acceleration (SHA), oculomotor (smooth pursuit and saccades), and water caloric testing. Subjects also underwent medication off-state dopamine transporter (DAT) imaging using N-(3-iodopro-2E-enyl)-2beta-carbomethoxy-3beta-(4'-methylphenyl) nortropane (PE2I) positron emission tomography (PET). Results of on and off state vestibular testing were analyzed using one tailed repeated measures t-tests. Significant findings were then used as outcome variables in a mixed linear model with distribution volume ratios (DVR) of striatal binding generated using PE2I PET imaging.

Results: Analysis revealed a significant difference between medication on state and off state VOR gain of the right eye during the 0.1 Hz smooth pursuit test (P< 0.05, Holm-Bonferroni corrected). No other significant differences were found. During medication off-state caloric testing, two participants demonstrated vestibular dysfunction whereas only one participant showed signs of vestibular dysfunction while on dopaminergic medications. Linear mixed modeling revealed a significant association between right eye VOR gain and medication state when adding baseline PE2I DVR of the left putamen into the interaction model (p<0.001, Bonferroni corrected).

Conclusions: VOR for the right eye during smooth pursuit at 0.1 Hz showed a decrease in gain from off to on dopaminergic states that was associated with increased PE2I binding in the left putamen. These findings suggest that velocity-dependent components of the VOR may partially be dopamine medication-responsive. Dopaminergic losses in the putamen may have contralateral implications on vestibular function. These findings demonstrate that dopaminergic medication state may only partially impact the outcome of vestibular testing while not changing the overall interpretation of the vestibular test. It is possible that aspects of vestibular dysfunction in PD may be differentially diagnosed due to dopaminergic supplementation. Further testing with a larger sample is necessary to elucidate the relationship between dopaminergic medication state and vestibular function.