Diagnostic value of video-oculography in progressive supranuclear palsy: a controlled study in 100 patients

Background The eponymous feature of progressive supranuclear palsy (PSP) is oculomotor impairment which is one of the relevant domains in the Movement Disorder Society diagnostic criteria. Objective We aimed to investigate the value of specific video-oculographic parameters for the use as diagnostic markers in PSP. Methods An analysis of video-oculography recordings of 100 PSP patients and 49 age-matched healthy control subjects was performed. Gain of smooth pursuit eye movement and latency, gain, peak eye velocity, asymmetry of downward and upward velocities of saccades as well as rate of saccadic intrusions were analyzed. Results Vertical saccade velocity and saccadic intrusions allowed for the classification of about 70% and 56% of the patients, respectively. By combining both parameters, almost 80% of the PSP patients were covered, while vertical velocity asymmetry was observed in approximately 34%. All parameters had a specificity of above 95%. The sensitivities were lower with around 50–60% for the velocity and saccadic intrusions and only 27% for vertical asymmetry. Conclusions In accordance with oculomotor features in the current PSP diagnostic criteria, video-oculographic assessment of vertical saccade velocity and saccadic intrusions resulted in very high specificity. Asymmetry of vertical saccade velocities, in the opposite, did not prove to be useful for diagnostic purposes.

Saccadic intrusions in amyotrophic lateral sclerosis (ALS)

The attempt to steadily fixate at a small visual object is continuously interrupted by a variety of fixational eye movements comprising, among others, a continuum of saccadic intrusions (SI) which ranges in size from microsaccades with amplitudes ≤0.25° to larger refixation saccades of up to about 2°. The size and frequency of SI varies considerably among individuals and is known to increase in neurodegenerative diseases such as neurodegenerative parkinsonism and amyotrophic lateral sclerosis (ALS). However, studies of ALS disagree whether also the frequency of SI increases. We undertook an analysis of SI in 119 ALS patients and 47 age-matched healthy controls whose eye movements during fixation and tests of executive functions (e.g antisaccades) had been recorded by video-oculography according to standardised procedures. SI were categorised according to their spatio-temporal patterns as stair case, back-and-forth and square wave jerks (a subcategory of back-and-forth). The SI of patients and controls were qualitatively similar (same direction preferences, similar differences between patterns), but were enlarged in ALS. Notably however, no increase of SI frequency could be demonstrated. Yet, there were clear correlations with parameters such as eye blink rate or errors in a delayed saccade task that suggest an impairment of inhibitory mechanisms, in keeping with the notion of a frontal dysfunction in ALS. However, it remains unclear how the impairment of inhibitory mechanisms in ALS could selectively increase the amplitude of intrusions without changing their frequency of occurrence.

Abnormal Saccadic Intrusions with Alzheimer's Disease in Darkness

Background: Classified as saccadic intrusions, Square-Wave Jerks (SWJs) have been observed during Visual Fixation (VF) in Alzheimer’s Disease (AD). However, the pathological significance of this phenomenon remains unclear. Objective: The present study analyzed the characteristics of SWJs in patients with AD with their eyes open in the dark without VF. Methods: Fifteen patients with AD and 15 healthy age- and sex-matched controls were investigated and compared. Saccadic intrusions with and without VF were detected as SWJs and measured using an electronystagmogram. Results: No significant difference in the frequency of SWJs was observed between control and AD groups with VF, but significantly more SWJs were observed in the AD group than in the control group in the absence of VF (p<0.01). In the control group, the frequency of SWJs was significantly higher with VF as compared to without VF. Conversely, the frequency in the AD group was significantly higher without VF. Furthermore, a directly proportional relationship was observed between the frequency of SWJs and higher-order function (R>0.55) in the AD group. Conclusion: SWJs without VF may have pathological significance in AD. In healthy individuals, SWJs are generated by VF and suppressed without VF. Conversely, in AD, SWJs are generated rather than suppressed in the absence of VF. These pathognomonic SWJs without VF also appear to be correlated with higher-order dysfunction, reflecting AD-related cortical damage. These findings suggest that pathological SWJs without VF observed in AD derive from cortical damage and may constitute an important marker of a higher-order function.

Saccadic Intrusions and Dysmetria

Saccadic dysmetria, intrusions, and oscillations are often encountered in association with certain cerebellar and neurodegenerative diseases. When severe, they can give rise to visual symptoms, such as difficulty with reading and oscillopsia. In this chapter, we begin by reviewing the clinical features of saccadic dysmetria, in which the saccadic amplitude is inappropriately calibrated. We next review the clinical features of saccadic intrusions and oscillations, which include square-wave jerks, macrosaccadic oscillations, ocular flutter, and opsoclonus. We review the common causes of these entities and discuss the diagnostic workup. Lastly, we discuss potential medical treatments to reduce the magnitude and frequency of saccadic intrusions and oscillations.