Oculomotor Fatigue and Neuropsychological Assessments mirror Multiple Sclerosis Fatigue

Abstract

Fatigue is a major complaint in MS. Up to now no objective assessment tools have been established which hampers any treatment approach. Previous work has indicated an association of fatigue with cognitive measures of attention. Oculomotor tests have been established in healthy individuals as a read-out of fatigue, and to some extent in MS patients. Based on these observations we compared two groups of MS patients, one with fatigue (n=28) and one without fatigue (n=21) and a group of healthy subjects (n=15) with a standardised computerised measure of alertness and an oculomotor stress test. Patients with fatigue showed highly significant changes of their saccade dynamics as defined by the Main Sequence and Phase Plane plots: They showed slowing of saccades, the characteristical fatigue double peak, and an asymmetrical phase plane. Oculomotor tests differentiated significantly between fatigue and fatigabiliy in our MS patients. They also showed significantly worse performance in the alertness test as well as in the oculomotor task. Significantly slower reaction times were observed for tonic alertness in 2 series without a cue (p=.025 and p=.037) but not in phasic alertness with a cue (p=.24 and p=.34). Performance was influenced by disability as well as by affective state. We conclude, when controlling for disability and depression, saccadic stress tests and alertness tests could be used as an objective read-out for fatigability and fatigue in MS patients.

Keywords: Eye Movements; Fatigue; Multiple Sklerosis; Neuropsychological assessment; Saccade velocity.

Figure 1.

Characteristics of amplitude, velocity, velocity/amplitude phase-plane of MS fatigue patient SC. Before [pre] and after [post] stress test (upper two rows). Median curves of 30 samples. For comparison, lowermost row shows corresponding graphs of a healthy subject (KF) after stress test, with normal dynamic and phase-plane graphs, even after the stress test. Note the saccadic amplitude reduction (arrow 1b) and significant reduction of peak velocity (2b) after the stress test, compared to before stress test (1a and 2a); falling below the two sigma main sequence limits of healthy subjects aged 20 to 60 in our lab. Note also the typical dynamical fatigue effects of the patient´s saccades with double velocity peaks (2b) [already slightly indicated before stress test (2a)]. Double saccades (3b) and asymmetrical (3a) phase-plane graphs demonstrate this result as well. Axes. Ordinates: Left: position, deg. Middle and right: velocity, deg/s. Abszissae: Time, 0 to 100 ms. Left vertical line depicts time when final saccadic amplitude has been reached: after 35ms (lowermost: normal), uppermost and middle (fatigue) after 50ms and 60ms respectively.

Figure 2.

Characteristics of Main Sequence (log-log) graphs of MS fatigue patient SC before [pre] and after [post] stress test (upper two graphs), and a normal healthy subject for comparison (lowest graph) [post] stress test. Each panel shows peak velocity in deg/s upper, and duration (sec) lower as functions of amplitude (deg). Note the saccadic amplitude reduction and significant reduction of peak velocity after the stress test; falling below the two sigma main sequence limits of healthy subjects aged 20 to 60 in our lab.