Vestibular Hypofunction in ARSACS Syndrome: A Possible Pitfall in the Differential Diagnosis of Recessive Cerebellar and Afferent Ataxias

Abstract

Objectives: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset ataxia characterized by cerebellar dysfunction, spasticity, and sensory-motor polyneuropathy due to variations in the SACS gene (13q11). To date, no studies have instrumentally assessed vestibular function in this condition.

Methods: We report a 36-year-old woman with diagnosis of ARSACS syndrome due to homozygous mutation (c.12232 C>T, p.Arg4078Ter) in the SACS gene. Neurologic examination showed spastic-ataxic gait, dysarthric speech, 4-limb ataxia, and spastic hypertonia with lower limb hyperreflexia.

Results: A vestibular instrumental evaluation including bedside oculomotor testing found gaze-evoked and rebound nystagmus on horizontal and vertical gaze, saccadic movements within normality ranges, saccadic pursuit, and slightly impaired visually enhanced vestibulo-ocular reflex (VVOR). A near-normal VOR suppression (VORS) was recorded. Neither head shakings, skull vibrations, nor supine positionings could evoke nystagmus. Finally, the video-head impulse test detected a symmetrical VOR impairment for all the semicircular canals (SCs), mostly involving the horizontal SCs, with corrective saccades in all planes.

Discussion: Vestibular hypofunction may be found in ARSACS syndrome and may represent a possible pitfall in the differential diagnosis of recessive cerebellar and afferent ataxias. In this setting, ARSACS syndrome should be considered in the differential diagnosis of CANVAS.

Figure 1. Brain MRI and Posturographic Study

(A) Sagittal and axial T1-weighted showing atrophy of the superior vermis and anterior lobes of the cerebellum; (B) posturographic study.

Figure 2. Analysis of Saccadic Movements

Analysis of saccadic movements using an ICS video-oculographic system (GN Otometrics, Denmark). Right eye position tracking and corresponding analyses of saccadic movements with areas in red squared background corresponding to age-related abnormality ranges. While the analysis shows slightly low mean values of peak velocity, mean values for accuracy/precision and latency are within normality ranges.

Figure 3. Video-Head Impulse Test Findings

vHIT measurements with an ICS video-oculographic system (GN Otometrics, Denmark) showing a bilateral and symmetrical VOR impairment involving all the semicircular canals, particularly both horizontal canals, with corrective saccades in all planes. Blue lines represent head impulses exciting left canals, orange lines correspond to impulses for right canals, green lines represent eye movements induced by the activation of VOR following each impulse, and red lines correspond to corrective saccades. The mean value of VOR gain (eye velocity/head velocity) is reported for each canal. The hexagonal plot in the center of the figure summarizes mean VOR gains for each canal. Impaired gains are shown in red. vHIT = video-Head Impulse Test; VOR = vestibulo-ocular reflex.