Ataxia with oculomotor apraxia type 2 (AOA2): an eye movement study of two siblings

Abstract

Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive disease due to mutations in the senataxin gene SETX (OMIM #606002), causing progressive cerebellar ataxia with peripheral neuropathy, cerebellar atrophy, oculomotor apraxia, and elevated alpha-fetoprotein (AFP) serum level [1]. Oculomotor apraxia is the ocular hallmark of the disease; when the head is free to move, patients make conspicuous thrusting head movements that are usually assumed to compensate for their inability to make normal voluntary eye movements. Quick phases of vestibular nystagmus and optokinetic nystagmus were assumed to be preserved in these patients [2], while the horizontal gaze failure is due to deficit in voluntary eye movements. These deficits can manifest as increased latency and/or hypometria of saccades with a staircase pattern [3]. Two siblings, a 12-year-old boy (in the following indicated with P1) and a 10-year-old girl (in the following indicated with P2), were referred to our neurologic ambulatory because of mild gait disturbances and incoordination. Neurologic examination together with laboratory, neuroimaging, and genetic tests uncovered an AOA2 diagnosis. Clinical, MRI, and genetic findings of both patients are already reported [4]. On neuro-ophthalmological examination, the afferent visual system was normal, while the efferent visual system showed gaze evoked and rebound nystagmus. A moderate head trusting was also seen in each sibling. Eye movements were recorded using an ASL-504 eyetracker device (Applied Science Laboratories, Bedford, MA, USA). Each recording session was preceded by an interactive calibration procedure based on nine static points and the relative validation. A visually guided GAP paradigm was used, with 200 ms of GAP before the target appearing in one of the four possible eccentric positions. Within a post-processing analysis, for each saccadic movement, we determined the following descriptive parameters: amplitude, accuracy, gain, duration, peak and mean velocity, and latency [5]. For the antisaccade (AS) tasks, we defined as a correct antisaccade the correct saccadic eye movement toward the opposite direction in respect to the visual target, for which we determined the latency, the gain, and accuracy; an erroneous prosaccade was the unsuppressed reflexive saccade toward the target; and a corrective antisaccade was the antisaccade made after an initial erroneous prosaccade. Moreover, the latency of correct AS and the number of erroneous prosaccades and of successive corrections were considered (Table 1). We also evaluated fixation abnormalities in terms of saccadic intrusions and nystagmus using a fixation task. Saccadic parameters of the two AOA2 patients, P1 and P2, were compared with the parameters of control populations (CNTRL). The control consisted of 8 healthy agematched subjects (2 males, 8 females) of mean age of 16.5 years. Differences in the saccadic parameters * A. Rufa [email protected]