Quantitative Oculomotor and Vestibular Profile in Spinocerebellar Ataxia Type 6 - Systematic Review and Meta-Analysis

Abstract

Whereas several studies have reported on quantitative oculomotor and vestibular measurements in spinocerebellar ataxia type 6 (SCA6), selecting the most suitable paradigms remains challenging. We aimed to address this knowledge gap through a systematic literature review and providing disease-specific recommendations for a tailored set of eye-movement recordings in SCA6. A literature search (MEDLINE, Embase) was performed focusing on studies reporting on quantitative oculomotor and/or vestibular measurements in SCA6-patients. Oculomotor and vestibular parameters were extracted and correlations with various epidemiologic and clinical parameters were sought. Twenty-two studies were included reporting on 154 patients. Abnormalities observed included reduced pursuit gain (58/69), frequent square-wave jerks (23/40), spontaneous downbeat nystagmus (DBN, 34/55) and triggered nystagmus including positional nystagmus (25/34) and vertical ("perverted") head-shaking nystagmus (21/34), gaze-evoked nystagmus (48/70) and angular vestibulo-ocular reflex (aVOR)-suppression (21/25), and high-frequency aVOR-deficits (26/33). For horizontal visually-guided saccades (VGS), changes in metrics (36/66) were frequently observed, whereas saccade velocity was usually preserved (39/44) and saccade latency within normal limits. Reduced high-frequency aVOR gains, VGS-latency and metrics correlated with disease severity. Longitudinal data indicated deterioration of individual video-head-impulse testing gains over time. A broad range of oculomotor and vestibular domains are affected in SCA6. Impairments in pursuit, saccade metrics, gaze-holding (gaze-evoked nystagmus, DBN) and high-frequency aVOR were most frequently identified and as such, should be prioritized as disease markers. Quantitative oculomotor testing in SCA6 may facilitate an early diagnosis and prove valuable in monitoring disease progression.

Keywords: Eye movement recordings; Hereditary ataxia; Oculomotor; Recommendations; Systematic review; Vestibular.

Fig. 1

*MEDLINE was accessed via PubMed. † Individual hand search of citation lists from selected studies and investigator files identified 17 additional manuscripts for review. ‡ Abstracts coded as “yes” or “maybe” by at least one reviewer were included in full-text review. § After full-text evaluation by two reviewers, any differences were resolved by discussion and – if needed—adjudication by a third, independent reviewer

Fig. 2

Frequency of oculomotor abnormalities amongst all SCA6 patients included. Thereby the number of SCA6-patients with abnormal (in blue) and normal (in red) findings for each oculomotor parameter is shown. Different oculomotor domains (pursuit eye movements, visually-guided saccadic eye movements, saccadic intrusions, eccentric gaze holding deficits, spontaneous and triggered nystagmus were grouped. Abbreviations: EGH = eccentric gaze holding; EM = eye movements; hor = horizontal; HSN = head-shaking nystagmus; OKN = optokinetic nystagmus; PEM = pursuit eye movements; PV = peak velocity; SCA6 = spinocerebellar ataxia type 6; SN = spontaneous nystagmus; vert = vertical

Fig. 3

Frequency of vestibular abnormalities amongst all SCA6 patients included. Thereby the number of SCA6-patients with abnormal (in blue) and normal (in red) findings for each vestibular parameter is shown. Different properties of the angular vestibulo-ocular reflex (aVOR) were grouped (low-frequency aVOR, aVOR suppression, high-frequency aVOR and caloric irrigation). Abbreviations: AC = anterior canal; aVOR = angular vestibulo-ocular reflex; CI = caloric irrigation; HC = horizontal canal; PC = posterior canal; SCC = semicircular canal; SPV = slow-phase velocity