The role of Ocular Movement Analysis in the differential diagnosis of Atypical Parkinsonian Disorders: a study on Multiple System Atrophy, Progressive Supranuclear Palsy and Corticobasal Degeneration

Atypical Parkinsonian Disorders (APD) are a group of neurodegenerative diseases characterized by progressive extrapyramidal symptoms and signs, unresponsive to levo-dopa and associated with a wide range of distinctive clinical features. According to the neuropathological substrate, APD may be classified in two broad categories of pathologies related to the accumulation of abnormal aggregates of proteins: the Alpha-synucleinopathies (Multiple-System Atrophy type C and P – MSA-C and MSA-P) and the Taupathies (Progressive Supranuclear Palsy - PSP and Corticobasal Degeneration - CBD). Due to the presence of overlapping clinical features, their differential diagnosis may often be challenging. Various oculomotor abnormalities, such as saccade dysmetria, increased latency, saccadic intrusions, nystagmus and vertical gaze palsy are often described in APDs with inconstant specificity. My aim was to determine peculiar changes in oculomotor profile that may help in distinguishing these disorders. I examined the eye movements of eleven patients with MSA-C, eight with MSA-P, twelve with PSP and six with CBD. Mean age of MSA-C patients was 58 (mean disease duration 3,7 years); in MSA-P, mean age was 65 (mean disease duration 3,7 years); in PSP group, mean age was 68 (mean disease duration 2 years); in CBD group, mean age was 67 (mean disease duration 2 years). Eye movement recording was obtained through an eye-tracker device (Applied Science Laboratories, Bedford, MA, USA); the visual target was a red dot on a black screen. Horizontal (±10°and 18°) and vertical (up/down 8°) visually-guided saccades, horizontal voluntary saccades (antisaccades) and fixation task were tested and statistically compared with EVAlab’s normative data obtained by healthy controls. As for saccades. standard saccadic parameters (latency, peak velocity, duration, gain and accuracy) were evaluated; moreover, presence of multistep saccades (i.e. saccades constitutes by two or more steps to reach the tardet) was assessed. For antisaccades, number of antisaccade errors with relative corrections, latency and gain of correct antisaccades, latency and gain of prosaccades erroneously directed toward the target and latency of corrective antisaccades were determined. Finally, eventual fixation changes (saccadic intrusions, nystagmus) were evaluated. MSA-C showed slight increased latency in reflexive and voluntary eye movements, with good performance in antisaccade task (low errors rate, high corrections rate). Velocity appeared to be preserved, whereas mild hypometria, with no more than two steps to reach the target, and poor accuracy, defined the saccadic profile. They had a lower number of SWJs in respect to PSP and MSA-P groups, but exhibited diverse forms of central nystagmus. MSA-P patients showed normal latency of reflexive eye movements, and prolonged latency of voluntary, associated to moderate to high range of errors and low percentage of corrections in the antisaccades. Hypometria with high frequency of multistep saccades, characterized by two or more steps to reach the target, and normal velocity defined the dynamic profile. Fixation appeared to be interrupted by SWJs, characterized by small amplitude and high frequency similar to PSP patients, but no nystagmus. Patients with PSP showed saccade slowing both in the horizontal and, more evidently, in the vertical plane, associated with prominent saccadic hypometria with very high range of multistep saccade (usually three of four), analogously defined by slow velocity. Vertical supranuclear palsy was common, so that some patients could not be recorded in the vertical plane. Latency was prolonged in both reflexive and voluntary tasks. Very high number of errors, with equally high number of corrections, characterized the antisaccade performance. Furthermore, PSP showed the highest rate of SWJs, peculiarly characterized by large amplitude and prolonged intersaccadic latency. CBD group made hypometric saccades with high frequency of multistep with two or more steps, and presented a mild saccade slowing. No supranuclear palsy was observable. Furthermore, they showed prominent increased latency in both reflexive and voluntary tasks; they were virtually incapable to perform antisaccade task, and exhibited the highest rate of errors and a very low rate of corrections. Finally, SWJs frequency was the lowest among groups. My findings substantiate peculiar changes of saccade dynamics in APDs, related to specific neuroanatomical substrate. Slowing and fragmentation of all ocular movements is the major finding in PSP patients, due to prominent atrophy of pons and, to a lesser extent, basal ganglia involvement. Saccades are of normal velocity but inaccurate in MSA, particularly MSA-C. MSA-P patients are more hypometric (lower gain and higher number of steps) than MSA-C, suggesting a greater basal ganglia involvement in the former, and a greater cerebellar impairment in the latter, also explaining the MSA-C low accuracy (dispersion of fixation around target) and the presence of central nystagmus. Latency and voluntary saccades performance are more impaired in PSP and particularly in CBD group than both MSA, suggesting a greater cortical impairment (particularly frontal and parietal cortex) in CBD. Saccadic intrusions are mostly typical of MSA-P and PSP, but they differed for the diverse amplitude (greater in PSP than MSA-P) and the intersaccadic latency (the latency between the first and second saccade of the intrusions, greater in PSP than MSA-P). Taken together, these abnormalities may help in configuring a peculiar disease “profile”. Qualitative and quantitative oculomotor profile examination may therefore be considered as a useful tool helping in differentiating ADPs with overlapping clinical features.