Oculomotor disorders in adult-onset Still's disease.

A patient with adult-onset Still’s disease (AOSD) developed periodic horizontal micro-saccadic oscillations and periodic rapid clockwise torsional eye movements followed by counterclockwise torsional drifts (see video). Neuroimaging studies were normal. Tests for paraneoplastic antibodies were negative. Details of the clinical presentation and experimental methods are presented in supplementary material 1. Horizontal saccades were faster than normal (supplementary material 2). There were bursts of horizontal saccadic oscillations without intersaccadic intervals (21.6 ± 0.4 Hz) and clockwise rapid torsional eye movement (top pole rotating towards the right ear) that had the same peak velocity-amplitude relationship as torsional quick phases of nystagmus (Fig. 1). These rapid torsional movements were followed by a drift (0.8 ± 0.2 deg/s) that brought the eyes to baseline. Low-frequency vertical and torsional oscillations were also seen (median: 3.4 and 3.1 Hz, respectively; Fig. 1b, d). The onset of rapid torsion and the horizontal saccadic oscillations were not always related (i.e., torsion did not trigger the horizontal oscillations or vice versa) (Fig. 2a). The median frequency of the pathological, spontaneous, horizontal saccadic oscillations during fixation (26.3 Hz) was not significantly different from the frequency of the physiological horizontal saccadic oscillations that are seen during orthogonal (vertical) saccades (21.9 Hz) (One-way ANOVA: p = 0.2) [6]. The median peak velocity of the pathological horizontal saccadic oscillations (14.8 deg/s) was significantly less than that of the corresponding horizontal saccadic oscillations during orthogonal (vertical) saccades (37.8 deg/s: One-way ANOVA: p 0.001; Fig. 2c). The median frequencies of the vertical (3.4 Hz) and torsional (3.1 Hz) pathological oscillations were lower than the corresponding frequencies of torsional (22.9 Hz) or vertical (21.6 Hz) oscillations during orthogonal (horizontal) saccades (One-way ANOVA: p 0.001; not shown in figure). A hypothesis to explain the pathophysiology of periodic saccadic oscillations in our patient is that saccadic burst neurons, excitatory burst neurons (EBN) and inhibitory burst neurons (IBN), comprise a reciprocally innervated premotor circuit. Their membranes contain ion channels that are important for the rebound increase in neural firing after transient external inhibition—post-inhibitory rebound (PIR) [4, 9]. Such reciprocal innervation and PIR make this neural circuit prone to oscillate [2, 3, 5–7]. We speculate that in our patient an immune mediated abnormal increase in the excitability of the burst neurons (either by reducing inhibition or increasing excitation) led to the bursts of pathological microsaccadic oscillations. Since the pattern of oculomotor dysfunction in our patient is not seen in all AOSD patients, just the presence of an immune mediated effect on burst neurons may not be sufficient to increase their excitability enough to cause oscillations. The patient might also need the appropriate genetic background (i.e., a Electronic supplementary material The online version of this article (doi:10.1007/s00415-009-5308-y) contains supplementary material, which is available to authorized users.