Journal of Neurology | 2021
The visually enhanced vestibulo-ocular reflex in CANVAS
Abstract
A well-known diagnostic problem in neuro-otology is the patient presenting with imbalance, without vertigo or hearing loss, who has impairment of the vestibulo-ocular reflex (VOR) from all six semicircular canals on clinical impulsive testing, confirmed on video head impulse testing (vHIT) [1]. The other eye movements look normal: pursuit looks smooth and there is no gaze-evoked nystagmus. The clinical visually enhanced vestibulo-ocular reflex (VVOR) test [2, 3] is equivocal and the patient can do a Romberg test on the floor but not on foam [4]. The patient admits to having movement-induced oscillopsia and remembers being in hospital 2 years ago for a urinary tract infection and receiving a parenteral antibiotic, but cannot remember which one. In this case, it would be useful to know if the VVOR is normal or abnormal; if it is abnormal then both VOR and smooth pursuit must be impaired, in which case Cerebellar Ataxia Neuropathy Vestibular Areflexia Syndrome (CANVAS) is a likely diagnosis [5]; if it is normal then gentamicin vestibulotoxicity [6] is a likely diagnosis. So, how can one test the VVOR accurately? What stimulus to use and what response to expect? We have tried measuring the VVOR using our standard vHIT apparatus (Natus ICS) and manually oscillating the patient’s head sinusoidally from side-to-side at about 0.3 Hz, then deriving horizontal VOR gain and catch-up saccades. In a normal subject, the gain close to 1.0 and there were almost no catch-up saccades at almost any frequency or peak velocity we chose to impose. Then we tried this in 3 patients we knew had gentamicin vestibulotoxicity and then in the 3 CANVAS patients, we report, to compare their results. We thought it would be possible to tell the difference [7], but it was not. It was too hard to oscillate the patient’s head, passively or actively, smoothly and sinusoidally, at a specific frequency and a specific peak velocity. So, to standardize the sinusoidal stimulus we decided to use our rotatory chair to produce a fixed-frequency sinusoidal stimuli (0.33 Hz) at six different peak chair velocities (10, 20, 30, 40, 50 and 60 deg/s) and to measure horizontal eye movement responses with the same Natus video-oculographic system we used for vHIT. Figure 1 shows this VVOR test in (A) normal subject, (B) in a gentamicin vestibulotoxicity patient and (C, D, E) in 3 CANVAS patients with increasing disease duration (4, 12 and 20 years) and severity of imbalance. Each CANVAS patient had a chronic cough, absent sural sensory action potentials with preserved Achilles tendon and sural H reflexes [8] and normal hearing for age and noise exposure. Each was positive for the RFC1 biallelic pathogenic AAGGG expansion [PMID309272] [9]. The data show that while the gentamicin toxicity patient had a normal VVOR even at 60 deg/s peak stimulus velocity, all 3 CANVAS patients had impaired VVOR even at 10 deg/s with the impairment was most marked at 60 deg/s. Figure 2 plots this graphically. The VVOR gain in the gentamicin patient was normal because her cerebellum was intact and so she could still generate a normal “VVOR” (i.e. smooth compensatory eye movements) with smooth pursuit alone. In contrast, the VVOR was impaired, highlighted by clinically observable catch-up saccades, at all stimulus velocities, in all 3 CANVAS patients, most severely in patient (E) who had the disease for the longest and had the worst balance. The message is that the VVOR is impaired only when both smooth pursuit and VOR are impaired. There are many possible causes of bilateral vestibular impairment; about 25% of these patients also have a cerebellar impairment or peripheral neuropathy or both [10] perhaps because they too have CANVAS. Both vestibular, * Gábor M. Halmágyi [email protected]