The effect of levodopa on saccades – Oxford Quantification in Parkinsonism study

Abstract

The evaluation of novel disease modifying drugs requires biomarkers that are simultaneously sensitive to disease state but resistant to the effects of background symptomatic treatment. Saccadic eye movement parameters have been proposed as a neurophysiological biomarker for Parkinson's disease (PD) and so it is important to know how they are affected by dopaminergic medication. Studies to date are conflicting: some have concluded that medication prolongs saccadic latencies while others suggest they are shortened. We aimed to characterise the effects of antiparkinsonian medication on prosaccadic and antisaccadic parameters in a large cohort of PD patients and age matched healthy controls and to survey the current literature in comparison to the study findings. Methods We studied saccades both off and on medication in 38 PD patients and 34 healthy controls (HC). Latencies, amplitudes, velocities, and directional errors were evaluated, using a published standardised protocol. We then combined this study and previously published literature in a metaanalysis of the effects of antiparkinsonian medication on prosaccadic latency (PSL). Results PSL is significantly prolonged by dopaminergic medication in PD, from a mean of 222.7 ms in the OFF medication state to a mean of 236.0 ms in the ON medication state (p=0.028). This effect size is comparable to the difference between PD OFF medication and healthy control values. There was no statistically significant change in any other saccadic parameter with medication. Of particular note, antisaccadic latency was almost exactly the same on and off medication (means of 414.9 ms and 417.2 ms respectively, p=0.97), while being almost 20% longer in PD patients compared to healthy controls (HC mean 357.2 ms; PD ON vs HC p=0.015; PD OFF vs HC p=0.0066).

Antisaccades in Parkinson’s Disease: A Meta-Analysis

“…While some studies demonstrated increased antisaccade error rates even in unmedicated patients in very early disease stages (Antoniades et al, 2015a;Hanuška et al 2019), others found no significant alterations of antisaccade latency or antisaccade error rate early and later in the disease course. (Ranchet et al, 2017;Nagai et al, 2019) As proposed by two recent studies (Lu et al, 2019;Waldthaler et al, 2019a), antisaccade latency might correlate with disease duration in PD without significant impact of dopaminergic medication.…”

“…CI confidence interval, HC healthy control group, PD group with Parkinson's disease, (m) mixed task design with prosaccades and antisaccades, SD standard deviation, Std. standardized ◂ (Briand et al, 1999), B14 (Bonnet et al, 2014b), B19 (Barbosa et al, 2019), C12 (Cameron et al, 2012), C00 (Crevits et al, 2000), E17 (Ewenczyk et al, 2017), G16 (Gorges et al, 2016), H10 (Harsay et al, 2010), H19 (Hanuška et al, 2019), L19 (Lu et al, 2019), L90 (Lueck et al, 1990), L16 (Lemos et al, 2016), M05 (Mosimann et al, 2005), N16 (Nemanich & Earhart, 2016), N19 (Nagai et al, 2019), R17 (Ranchet et al, 2017), RP15 (Rivaud-Péchoux et al, 2007), V19 (Visser et al, 2019), vK09 (van Koningsbruggen et al, 2009, W15 (Walton et al, 2015), W16 (Wang et al, 2016), W19 (Waldthaler et al, 2019a)…”

“…However, they did not replicate the decreasing effect of levodopa on antisaccade latency in their own study. (Lu et al, 2019) While antisaccade error rates might decrease after levodopa intake (Hood et al, 2007), STN-DBS studies provided inconsistent results regarding changes in antisaccade error rates. (Antoniades et al, 2015b;Goelz et al, 2017) To shed light upon the high variability of antisaccade performance in PD, we conducted a comprehensive meta-analysis.…”

Antisaccade Latency Is Sensitive to Longitudinal Change of Motor and Cognitive Symptoms in Parkinson's Disease

“…Building on earlier studies that have already proposed antisaccade measures as markers for PD severity, 5,6 we provide first data indicating that antisaccade latency may be sensitive to longitudinal intraindividual improvement and deterioration of motor and cognitive symptoms in PD. Our preliminary results pave the way for future longitudinal studies with larger cohorts and longer follow-up periods.…”

How deep brain stimulation and levodopa affect gait variability in Parkinson’s disease

“…The SC is a critical structure in the generation of saccades, the rapid conjugate eye movements that shift gaze. Saccades have been studied extensively in PD (33-36) and more specifically in PD patients who have had DBS (37-39). The most commonly used experimental task is the visually guided prosaccade, in which the subject moves their eyes as quickly as possible towards a novel visual target.…”