Jae-Myung Kim; Alexander Andrea Tarnutzer; Seung-Han Lee

doi:10.21790/rvs.2025.003

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Vestibulo-ocular reflex findings in key subtypes of hereditary cerebellar ataxia: a review: Jae-Myung Kim¹, Alexander Andrea Tarnutzer^2,3, Seung-Han Lee¹; Research in Vestibular Science 2025;24(2):79-88.
DOI: https://doi.org/10.21790/rvs.2025.003
Published online: June 15, 2025

¹Department of Neurology, Chonnam National University Hospital and Chonnam National University Medical School, Gwangju, Korea

²Department of Neurology, Cantonal Hospital of Baden, Baden, Switzerland

³Faculty of Medicine, University of Zurich, Zurich, Switzerland

Corresponding author: Seung-Han Lee Department of Neurology, Chonnam National University Hospital, 42 Jebong-ro, Dong-gu, Gwangju 61469, Korea. E-mail: nrshlee@chonnam.ac.kr

• Received: February 3, 2025 • Revised: April 29, 2025 • Accepted: May 18, 2025

This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Abstract
INTRODUCTION
REPRESENTATIVE HEREDITARY CEREBELLAR ATAXIAS WITH VESTIBULAR DYSFUNCTION
SUMMARY AND CONCLUSION
ARTICLE INFORMATION
REFERENCES

Abstract

Vestibulo-ocular reflex (VOR) impairments are common in central vestibular disorders and may provide critical insights into disease-specific pathophysiology and diagnosis. Recent advances in quantitative VOR and oculomotor measurement techniques, such as video head impulse testing and video-oculography, have further enhanced the accuracy and efficiency of these assessments. This is particularly important in the field of hereditary cerebellar ataxia, where definitive diagnosis still depends on genetic testing due to significant overlap in clinical phenotypes and considerable variability. This review focuses on four representative subtypes selected based on both global prevalence and the predominance of vestibular dysfunction, as evaluated by quantitative assessments: spinocerebellar ataxia type 3 (SCA3), SCA6, Friedreich ataxia (FRDA), and cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS). Quantitative vestibular assessments revealed distinct patterns of VOR impairment. SCA3 and CANVAS consistently show markedly reduced angular VOR (aVOR) gains across all stimulation frequencies and measurement techniques. In contrast, FRDA demonstrates aVOR impairments primarily during high-frequency stimuli, with inconsistent low-frequency responses. SCA6 is characterized by frequent high-frequency aVOR impairments, predominantly affecting horizontal and posterior canals, while low-frequency responses remain variable. Notably, aVOR suppression (VOR cancellation) is severely impaired in SCA6 and in approximately half of FRDA cases, but relatively preserved in SCA3 and CANVAS, offering a potential marker for differential diagnosis. An integrated assessment of vestibular and oculomotor findings may provide valuable diagnostic clues. This review aims to assist clinicians and researchers in understanding the characteristic VOR profiles of key hereditary cerebellar ataxias.
Keywords: Spinocerebellar ataxia; Friedreich ataxia; Vestibular diseases; Vestibulo-ocular reflex

INTRODUCTION

Hereditary cerebellar ataxias are a heterogeneous group of disorders characterized by progressive cerebellar ataxia, often accompanied by various additional neurological deficits [1]. While several subtypes may present with distinctive clinical features such as macular pigmentary degeneration in spinocerebellar ataxia (SCA) type 7, molecular diagnosis has been established as the gold standard for diagnosis, as there is considerable overlap in the clinical phenotypes among genetic subtypes [1,2]. Signs of vestibular and oculomotor impairment have been observed in hereditary cerebellar ataxias in association with the affected cerebellar/brainstem regions (e.g., the vestibulo-cerebellum including the flocculo-nodular lobe, or the brainstem vestibular nucleus) [3]. Vestibular and oculomotor deficits may exacerbate the disabilities caused by cerebellar ataxia, further compromising the patient’s quality of life and increasing the risk of falls. Therefore, identifying these features in hereditary cerebellar ataxia patients may be crucial, as they may also serve as diagnostic clues for estimating specific types of hereditary cerebellar ataxia [1,3]. Furthermore, recent advances in laboratory tests, particularly in vestibular and oculomotor function tests such as the video head impulse test (HIT) and video-oculography facilitate objective documentations and minimize interobserver variability [4]. These quantitative oculomotor assessments have become sensitive tools for tracking disease progression, detecting early intervention efficacy, and differentiating ataxia diagnoses, including the preataxia stage [3]. Finally, together with the increasing availability of video HIT and video-oculographic devices, the improved sensitivity and accumulated data of these assessments make them promising digital biomarkers for diagnosis and treatment trials of ataxia [3].

In this review, we included subtypes of hereditary cerebellar ataxia through a literature review considering both their global prevalence of the disease and the predominance of vestibular dysfunctions, which have been well-documented using adequate measurement techniques. In addition, we aimed to focus on cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) and related differential diagnoses, such as SCA type 3 (SCA3) and Friedreich ataxia (FRDA), where vestibular and cerebellar impairments frequently coexist. We present the major findings from quantitative vestibular assessments (e.g., HIT using either video HIT device or magnetic search coil, rotatory chair test, and caloric test) in the representative subtypes, along with discussing underlying pathomechanisms and their clinical significance.

REPRESENTATIVE HEREDITARY CEREBELLAR ATAXIAS WITH VESTIBULAR DYSFUNCTION

Spinocerebellar Ataxia Type 3

SCA3, also known as Machado-Joseph disease, is the most common autosomal dominant cerebellar ataxia, caused by the expansion of CAG trinucleotide repeats in the ATXN3 gene [5]. Vestibulo-ocular reflex (VOR) impairment in SCA3 has been reported as a core clinical feature across all stimulation frequencies (either low or high Hz) and measurement techniques (i.e., caloric test, HIT), as illustrated in Table 1 and Fig. 1 [1,5-10]. Moreover, aVOR gain (measured by video HIT) progressed significantly during the preataxic phase, suggesting their potential as a preclinical biomarker in SCA3 [9,10]. Therefore, SCA3, characterized by cerebellar ataxia accompanied by vestibular dysfunction, has been considered as part of the differential diagnosis for CANVAS. Previous studies with quantitative HIT using either a video HIT device or magnetic search coils showed significantly decreased angular VOR (aVOR) gains for both horizontal and vertical canals. This reduction in aVOR gains was observed in 80% to 100% of the tested subjects, and it was associated with abnormal catch-up saccades [1,6,8,11]. One study also revealed decreased aVOR gains for horizontal canals (HCs) on the suppression head impulse test but preserved sacculocollic function on cervical vestibular-evoked myogenic potentials (cVEMPs) [6]. Rotatory chair tests demonstrated decreased aVOR gains (fraction of affected cases, 28.6%–83.3%), and caloric tests showed reduced or absent caloric response (57.9%–100%) [5,11-14]. Otholithic function assessed by cVEMPs and ocular vestibular-evoked myogenic potentials (oVEMPs) revealed severely impaired responses in most study patients (93%) in one study [15]. On the other hand, prior studies showed none to mild impairment of aVOR cancellation only when compared to healthy controls [11,14]. The aVOR gain (especially for HCs during video HITs) was negatively correlated with the CAG repeat length and disease severity (assessed by the Scale for the Assessment and Rating of Ataxia [SARA], Neurological Examination Score for Spinocerebellar Ataxia [NESSCA], and International Cooperative Ataxia Rating Scale [ICARS]) [1,8,9,12]. Abnormal bedside catch-up saccades were also correlated with decreased aVOR gains measured using magnetic search coils [7].

The possible mechanisms of global impairment of the VOR in SCA3 may be ascribed to the neurodegeneration of both the medial vestibular nucleus and the nucleus prepositus hypoglossi, the brainstem neural integrator, or the bilateral involvement of primary vestibular neurons (see Table 2 for a summary of presumed anatomical structures and VOR dysfunction types) [1,5,7,14,16]. During eye-head tracking, VOR could be cancelled in normal control by a smooth pursuit signal, and a partial, parametric reduction of VOR gain [17]. On the other hand, patients with severe vestibular loss lack a VOR to cancel during eye-head pursuit; consequently, there is no requirement for them to generate an ocular smooth pursuit signal during such movements [17]. Notably, some patients with absent vestibular function demonstrate better eye-head tracking performance compared to smooth pursuit with the head stationary [17]. Similarly, although most patients with hereditary cerebellar ataxia present with smooth pursuit deficits, certain subtypes with prominent VOR impairments such as SCA3 may exhibit normal or only mildly impaired VOR cancellation [11]. This finding suggests that VOR cancellation mechanisms may remain relatively preserved even in the setting of profound vestibular loss, providing a potential clinical clue for differential diagnosis in these patients.

Spinocerebellar Ataxia Type 6

SCA6 has been described as pure cerebellar ataxia without definite brainstem signs or involvement on brain magnetic resonance imaging and is caused by CAG repeat expansion in the CACNA1A gene [18]. The onset of symptoms might occur after the age of 50 years in a considerable number of patients; thus, the late onset of symptoms may obscure the hereditary nature of the disease and clinicians may have difficulty distinguishing it from idiopathic sporadic cerebellar ataxia [18]. Previous results regarding the vestibular performance in SCA6 showed asymmetric VOR damage [1,14,19-21] (Table 1). In detail, impaired aVOR gains during quantitative HITs for at least one semicircular canal were very frequent (79%), and more prevalent in the posterior canals (PCs) than in the anterior canals (ACs) in some studies [1,19,21]. From the perspective of individual semicircular canals, most patients exhibited reduced aVOR gains, particularly in more severe cases, while some less severely affected patients showed increased aVOR gains, specifically in the HCs or ACs [21]. But no cases of increased aVOR gains have been observed in the PCs [21]. One study revealed a relative increase in aVOR gains during HITs in mildly affected patients, while a decrease in aVOR gains was observed in more severely affected patients [20]. Another study demonstrated that initial aVOR gains for the ACs and HCs during HITs were mostly normal or increased and then decreased during follow-up, while those for the PCs decreased from the initial study and remained unchanged [19]. In contrast, hyperactive responses to the caloric test were frequent, while low-frequency aVOR (assessed by the rotatory chair test) was usually normal or increased only on rare occasions [21]. Fixation suppression of the aVOR was also severely impaired in SCA6 (84%) [14,20-22]. One study showed a markedly reduced linear VOR in all patients evaluated by transient linear whole body acceleration along the interaural axis [23]. The aVOR gains during quantitative HITs showed a negative correlation with disease severity (assessed by the SARA and ICARS) in several studies [19-21], whereas one study did not observe this correlation [1]. In contrast, the vestibular responses to low-frequency stimuli (i.e., caloric test, rotatory chair test) were normal or increased regardless of the disease severity (assessed by the ICARS) [14,20]. SCA6 patients showed significantly reduced otolithic sensitivity and almost no modulation of the linear VOR (induced by transient linear high acceleration along the interaural axis) by vergence angle compared to normal controls, suggesting the involvement of a cerebellar-mediated otolith pathway in addition to the weaker direct otolith pathway [23].

Selective impairment of the aVOR during HITs (high-frequency stimuli) in SCA6 may be associated with neurodegeneration of the flocculus [1,19,20]. Previous studies suggested that the reduced aVOR gains with high-frequency stimuli might be ascribed to a frequency-dependent VOR enhancement of the flocculus [24,25]. Moreover, the inhibitory projections of Purkinje cells in the flocculus and the ventral paraflocculus to specific secondary vestibular nuclei are more prominent for the AC and HC pathways than for the PC pathway [24]. Consequently, the loss of these inhibitory projections to the AC pathway may lead to higher gains for downward impulses compared to upward impulses and may explain a significant decrease in the aVOR gains for the PCs than the ACs during HITs [1,19,20,24].

Friedreich Ataxia

FRDA is the most common form of autosomal-recessive ataxia, mostly caused by abnormal GAA repeat expansions in the FXN gene [26]. Meanwhile, the prevalence of FRDA is extremely rare in East Asia and has not yet been reported in South Korea [27]. Compared to other hereditary cerebellar ataxias mentioned above, FRDA typically manifests in puberty and slowly progresses over decades [26]. VOR impairments in FRDA are common and are known to be one of its characteristic features [8,26,28,29]. However, unlike in SCA3 and similar to SCA6, FRDA may show discrepancies in aVOR responses depending on the stimulation frequency [8,26,28] (Table 1). Clinical and quantitative HITs using the magnetic search coil results showed globally decreased aVOR gains and prolonged latencies for all semicircular canals with abnormal catch-up saccades [8,26,28]. Middle-frequency stimuli measured by the Earth’s vertical axis rotation (EVAR) showed a reduced time constant compared to healthy controls [28]. Otolithic function as assessed by cervical VEMPs might also be severely impaired in FRDA [28]. On the other hand, previous studies studying responses to low-frequency stimuli applied by the caloric test showed inconsistent results [8,26,28-30]. While some studies reported normal caloric responses, others observed bilaterally reduced slow-phase velocities, suggesting that caloric responses in FRDA can range from normal to diminished, likely due to differences in disease stage, individual characteristics, and testing methodologies [29]. While earlier studies suggested preserved aVOR suppression by fixation in FRDA [28,31], a recent systematic review reported impaired aVOR suppression in approximately 52% of patients, suggesting that this deficit may be a common feature of FRDA [29]. Abnormal auditory nerve function, as assessed by auditory brainstem evoked potentials, has been demonstrated in FRDA, while cochlear function remains preserved [26,28,30,32,33]. One prior study showed a negative correlation between the disease duration and the time constant of EVAR responses [28]. Also, abnormal clinical HIT findings were more frequent in patients with a longer disease duration and more severe cerebellar impairment (assessed by the SARA, ICARS, and Friedreich Ataxia Rating Scale [FARS]) [28]. The deficiency in yaw axis gain and the prolonged latency correlated with increased horizontal saccadic latency [26].

Based on previous results, it is difficult to conclude that the cause of VOR dysfunction in FRDA is entirely peripheral or central [26,28]. More likely, it is a combined peripheral vestibular and central cerebellar impairment that results in the typical phenotype. Indeed, histopathological studies in FRDA demonstrated gliosis in the vestibular nucleus, abnormalities of the spiral ganglion, and the vestibular nerve [26,30,32,34]. Further research is required to localize and elucidate the pathomechanism of VOR impairment in FRDA.

Cerebellar Ataxia with Neuropathy and Vestibular Areflexia Syndrome

CANVAS is a slowly progressive ataxic disorder characterized by cerebellar dysfunction, bilateral vestibulopathy, and somatosensory deficits [35,36]. Subsequently, an autosomal-recessive repeat expansion in intron 2 of the RFC1 gene, which plays a crucial role in DNA replication and repair, was identified as the main genetic cause of CANVAS [37,38]. Recently, the first genetically confirmed case in South Korea was reported [39] (Fig. 2).

Visually-enhanced VOR impairment, as a result of compensatory smooth eye movement mechanism failure (i.e., pursuit eye movements, optokinetic reflex) as well as VOR impairment are known to be the most characteristic clinical signs in CANVAS [36,37,40]. The VOR in CANVAS consistently showed prominent damage irrespective of the stimulation frequency [36,37,41-43] (Table 1). Horizontal nystagmus responses both to bithermal caloric stimulation and to constant acceleration rotational testing were severely reduced or absent in all patients tested [42]. Quantitative HITs either using magnetic search coils or a video HIT device demonstrated decreased aVOR gains, associated with abnormal catch-up saccades, for both the horizontal and vertical canals [41-43]. Moreover, a previous study showed that bilateral vestibulopathy might precede cerebellar ataxia in affected patients and could be an initial presenting sign with genetically confirmed CANVAS [41].

Compared to heterozygous intronic repeat expansions in the FGF14 gene-associated disease (also known as SCA27B), which shares phenotypic overlap with CANVAS, the severity of bilateral vestibulopathy (as indicated by reduced VOR gain measured by video HIT) is significantly greater in CANVAS [44]. This difference may reflect distinct pathomechanisms and serve as a valuable clinical factor for differentiating the two diseases [44].

Similar to SCA3, aVOR suppression has been reported normal in CANVAS [35,36]. On the other hand, otolithic function in CANVAS, assessed through cervical and ocular VEMPs, exhibited inconsistent outcomes ranging from absent responses to bilaterally symmetric responses on both cervical and ocular VEMPs, with amplitudes differing between tests [45-47].

Temporal bone histopathological studies of CANVAS revealed marked loss of vestibular (Scarpa’s) ganglion cells with preservation of vestibular receptor hair cells and vestibular nuclei, consistent with vestibular neuronopathy without involving the auditory system [48]. These findings suggest that vestibular impairment in CANVAS is associated with a combined peripheral vestibular and cerebellar pathology. This could serve as a differentiating factor from other hereditary cerebellar ataxias with vestibular impairment (i.e., SCA3, SCA6), which primarily show central vestibular pathology involving the vestibular nuclei [48]. To aid clinical interpretation, we summarized the presumed anatomical origin and types of VOR impairment for each disease in Table 2.

SUMMARY AND CONCLUSION

VOR impairments are common in several subtypes of hereditary cerebellar ataxia, but specific patterns show substantial variability depending on the genetic characteristics [1,3]. In SCA3 and CANVAS, aVOR gains were consistently reduced across all stimulation frequencies and measurement techniques. In FRDA, significant aVOR impairments were observed for high-frequency stimuli, while responses to low-frequency stimuli were inconsistent. In SCA6, aVOR impairment during high-frequency stimuli was very common, affecting at least one semicircular canal, with a greater impact on the HCs and PCs than on the ACs. However, responses to low-frequency stimuli were either normal or enhanced regardless of disease severity. Furthermore, in the context of vestibular function, distinguishing among the four representative genotypes may be facilitated by analyzing the clinical patterns of aVOR impairment in combination with aVOR suppression (so-called VOR cancellation), which was severely impaired in SCA6 and in approximately half of FRDA cases, but relatively preserved in SCA3 and CANVAS.

However, a major obstacle in studying clinical biomarkers of hereditary cerebellar ataxia is the variability observed even within the same genotype, influenced by factors such as the study population (e.g., ethnicity), type of genetic mutation, and disease severity (stage) [3,21]. Therefore, large-scale prospective studies would be necessary to address these limitations. Additionally, in the field of neuro-otologic biomarkers, integrating convergence analysis with oculomotor findings is essential to enhance diagnostic accuracy and to clarify the underlying pathomechanisms [3,21]. In conclusion, the assessment of the VOR in hereditary cerebellar ataxia may aid in the differential diagnosis, broaden understanding of the disease-specific pathophysiology, and predict disease progression in particular subtypes.

ARTICLE INFORMATION

Funding/Support

This study was financially supported by the Chonnam National University (grant number: 2024-0440).

Conflicts of Interest

Jae-Myung Kim and Alexander Andrea Tarnutzer are Editorial Board members, and Seung-Han Lee is an Associate Editor of Research in Vestibular Science; they were not involved in the review process of this article. The authors declare no other conflicts of interest.

Availability of Data and Materials

The datasets are not publicly available but are available from the corresponding author upon reasonable request.

Authors’ Contributions

Conceptualization: Kim JM, Lee SH; Data curation: All authors; Funding acquisition, Methodology: Lee SH; Visualization: Kim JM; Writing – Original Draft: Kim JM; Writing – Review & Editing: Tarnutzer AA, Lee SH.

All authors read and approved the final manuscript.

Fig. 1.

Neuroimaging and vestibulo-ocular reflex (VOR) findings of a patient with spinocerebellar ataxia type 3 (SCA3; representative case). (A) A sagittal T1-weighted brain magnetic resonance image of the patient demonstrates diffuse cerebellar and brainstem atrophy. (B) Bithermal caloric test shows bilateral weak responses without significant asymmetry (sum of the peak, slow-phase velocity [SPV]: right ear=6.5°/sec, left ear=5.4°/sec) (C) Video head impulse test reveals globally decreased VOR gains in all six semicircular canals, along with abnormal overt and covert catch-up saccades when testing the horizontal canals (HCs). Reduced VOR gains were defined as: (1) the sum of the peak SPV <12°/sec during four stimulation conditions during the bithermal caloric test, and (2) <0.8 and <0.7 for the horizontal and vertical canals, respectively, during the video head impulse test. AC, anterior canal; PC, posterior canal.

Fig. 2.

Neuroimaging and vestibulo-ocular reflex (VOR) findings of a patient with cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS; representative case). (A) Sagittal T1-weighted magnetic resonance imaging indicated mild atrophy in the superior cerebellar vermis. (B) Bithermal caloric tests indicated complete canal paralysis bilaterally. (C) Video head impulse testing revealed severely decreased VOR gains for all six semicircular canals along with covert and overt corrective saccades. (D) The visually-enhanced VOR was impaired, with corrective catch-up saccades during passive head oscillation. AC, anterior canal; HC, horizontal canal; HEP, horizontal eye position; HEV, horizontal eye velocity; PC, posterior canal; Rt., right; Lt., left; SPV, slow-phase velocity. Reproduced from the article of Yun et al. [39], according to the Creative Commons License.

Table 1.

Summary of VOR findings in key subtypes of hereditary cerebellar ataxia

Subtype	Acceleration stimuli	Method	Major findings (% of findings being present)	Clinical correlation	Reference
SCA3	High-frequency aVOR	vHIT or MSC	Decreased aVOR gains for all SCCs (MSC, 80%–100%; vHIT, 83.3%–85.7%)	Negative correlation between the aVOR gain (vHIT, especially HC) and the severity of disease (SARA)	1, 6-8, 11
		vHIT or MSC	Abnormal, with presence of CS (83.3%–86.7%)		1, 6-8, 11
		Clinical HIT	Abnormal, with presence of CS (80%–100%)	Bedside CSs correlated with decreased aVOR gains (MSC)	5, 7
	Low- to intermediate-frequency aVOR	RCT	Decreased aVOR gain (28.6%–83.3%)	Negative correlation between the aVOR gain and the CAG repeat length	11, 12, 14
	Low- to intermediate-frequency aVOR	Caloric test	Reduced or absent response (57.9%–100%)	No correlation between the vestibular areflexia and the cerebellar impairment (ICARS)	5, 12
SCA6	High-frequency aVOR	vHIT or MSC	aVOR gains were increased in the mild cases and decreased in the severe cases (MSC)	aVOR gains (MSC) were negatively correlated with the severity of disease (ICARS)	1, 19, 20
			Very frequent aVOR Impairment of at least one SCC (vHIT, MSC)	aVOR gains (vHIT) for each canal showed a negative correlation with the severity of disease (SARA)
			Preferential impairment of PC aVOR gains (vHIT)	aVOR gains (vHIT) for the PCs with CS in the PCs were significantly lower than the aVOR gains with no CS
				The differences in the head impulse aVOR gains (vHIT) were larger between the ACs and PCs in those with^a) perverted HITs than in those without
	Low- to intermediate-frequency aVOR	RCT, caloric test	Normal to increased aVOR gain regardless of the disease severity (RCT, caloric test)	No correlation between the aVOR gain and clinical parameters (RCT, caloric test)	14, 20
	Low- to intermediate-frequency aVOR	RCT, caloric test	Normal aVOR gain (100%, RCT)		14, 20
	Linear VOR	Linear acceleration of the whole body along the interaural axis (MSC)	Normal LVOR latency, but decreased sensitivity. Catch-up saccades were generated	Not available	23
FRDA	High-frequency aVOR	vHIT or MSC	Prolonged aVOR latency and decreased aVOR gain for all SCCs (MSC)	HC gain reduction and the prolonged aVOR latency correlated with increased horizontal saccadic latency (MSC)	8, 26
		vHIT or MSC	Decreased aVOR gain (100%), prolonged aVOR latency, abnormal CS (vHIT)		8, 26
		Clinical HIT	Abnormal HIT (54.8%)	Abnormal HIT is more frequently observed in patients with longer disease duration and in patients with higher FARS, ICARS, and SARA scores	28
	Low- to intermediate-frequency aVOR	EVAR	Significantly lower mean time constant than in healthy controls	Time constant of EVAR responses decreased with the duration of the disease	28
	Low- to intermediate-frequency aVOR	Caloric test	Reduced aVOR gain (41%)	Not available	29
CANVAS	High-frequency aVOR	vHIT or MSC	Decreased aVOR gain (100%) for all SCCs with abnormal CS (MSC, vHIT)	Negative correlation between the aVOR gain and disease duration (vHIT)	36, 41, 42, 46
	High-frequency aVOR	vHIT or MSC	Decreased VVOR gain (MSC, vHIT)		36, 41, 42, 46
	Low- to intermediate-frequency aVOR	RCT, Caloric test	Absent or severely reduced horizontal nystagmus responses (100%, RCT, caloric test)	Not available	42

SCA3, spinocerebellar ataxia type 3; aVOR, angular vestibulo-ocular reflex; VOR, vestibulo-ocular reflex; SCC, semicircular canal; MSC, magnetic search coil; vHIT, video head impulse test; CS, catch-up saccade; SARA, Scale for the Assessment and Rating of Ataxia; HIT, head impulse test; RCT, rotatory chair test; ICARS, International Cooperative Ataxia Rating Scale; SCA6, spinocerebellar ataxia type 6; PC, posterior canal; AC, anterior canal; LVOR, linear vestibulo-ocular reflex; FRDA, Friedreich ataxia; FARS, Friedreich Ataxia Rating Scale; EVAR, Earth’s vertical axis rotation; CANVAS, cerebellar ataxia with neuropathy and vestibular areflexia syndrome; VVOR, visually enhanced vestibulo-ocular reflex.

^a)Perverted HIT was defined as the eyes moved upward in addition to horizontally, producing a “cross-coupled” VOR during the horizontal head impulse.

Table 2.

Presumed anatomical origin and type of VOR impairment in hereditary cerebellar ataxias

Disease subtype	Presumed responsible anatomical structures	Type of VOR impairment (central/peripheral/mixed)	Reference
SCA3	Medial vestibular nucleus, nucleus prepositus hypoglossi, possible involvement of primary vestibular afferents	Central±peripheral	1, 5, 7, 14, 16
SCA6	Flocculus, paraflocculus (vestibulo-cerebellum)	Central	1, 19, 20
FRDA	Vestibular nuclei, vestibular nerve, spiral ganglion	Mixed (central+peripheral)	26, 28, 30, 32, 34
CANVAS	Vestibular (Scarpa’s) ganglion, cerebellar vermis	Mixed (peripheral+central)	42, 46, 48

VOR, vestibulo-ocular reflex; SCA3, spinocerebellar ataxia type 3; SCA6, spinocerebellar ataxia type 6; FRDA, Friedreich Ataxia, CANVAS, cerebellar ataxia neuropathy vestibular areflexia syndrome.

The anatomical origin is presumed based on current clinical, neurophysiological, and pathological evidence, and may vary depending on individual cases.

‘Central’ indicates dysfunction primarily at the level of the cerebellum or brainstem vestibular structures. ‘Peripheral’ refers to dysfunction at the level of the vestibular nerve or labyrinthine structures. ‘Mixed’ indicates involvement of both central and peripheral vestibular pathways.

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Vestibulo-ocular reflex findings in key subtypes of hereditary cerebellar ataxia: a review

Res Vestib Sci. 2025;24(2):79-88. Published online June 15, 2025

DOI: https://doi.org/10.21790/rvs.2025.003

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Vestibulo-ocular reflex findings in key subtypes of hereditary cerebellar ataxia: a review

Fig. 1. Neuroimaging and vestibulo-ocular reflex (VOR) findings of a patient with spinocerebellar ataxia type 3 (SCA3; representative case). (A) A sagittal T1-weighted brain magnetic resonance image of the patient demonstrates diffuse cerebellar and brainstem atrophy. (B) Bithermal caloric test shows bilateral weak responses without significant asymmetry (sum of the peak, slow-phase velocity [SPV]: right ear=6.5°/sec, left ear=5.4°/sec) (C) Video head impulse test reveals globally decreased VOR gains in all six semicircular canals, along with abnormal overt and covert catch-up saccades when testing the horizontal canals (HCs). Reduced VOR gains were defined as: (1) the sum of the peak SPV <12°/sec during four stimulation conditions during the bithermal caloric test, and (2) <0.8 and <0.7 for the horizontal and vertical canals, respectively, during the video head impulse test. AC, anterior canal; PC, posterior canal.

Fig. 2. Neuroimaging and vestibulo-ocular reflex (VOR) findings of a patient with cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS; representative case). (A) Sagittal T1-weighted magnetic resonance imaging indicated mild atrophy in the superior cerebellar vermis. (B) Bithermal caloric tests indicated complete canal paralysis bilaterally. (C) Video head impulse testing revealed severely decreased VOR gains for all six semicircular canals along with covert and overt corrective saccades. (D) The visually-enhanced VOR was impaired, with corrective catch-up saccades during passive head oscillation. AC, anterior canal; HC, horizontal canal; HEP, horizontal eye position; HEV, horizontal eye velocity; PC, posterior canal; Rt., right; Lt., left; SPV, slow-phase velocity. Reproduced from the article of Yun et al. [39], according to the Creative Commons License.

Fig. 1.

Fig. 2.

Vestibulo-ocular reflex findings in key subtypes of hereditary cerebellar ataxia: a review

Subtype	Acceleration stimuli	Method	Major findings (% of findings being present)	Clinical correlation	Reference
SCA3	High-frequency aVOR	vHIT or MSC	Decreased aVOR gains for all SCCs (MSC, 80%–100%; vHIT, 83.3%–85.7%)	Negative correlation between the aVOR gain (vHIT, especially HC) and the severity of disease (SARA)	1, 6-8, 11
		vHIT or MSC	Abnormal, with presence of CS (83.3%–86.7%)		1, 6-8, 11
		Clinical HIT	Abnormal, with presence of CS (80%–100%)	Bedside CSs correlated with decreased aVOR gains (MSC)	5, 7
	Low- to intermediate-frequency aVOR	RCT	Decreased aVOR gain (28.6%–83.3%)	Negative correlation between the aVOR gain and the CAG repeat length	11, 12, 14
	Low- to intermediate-frequency aVOR	Caloric test	Reduced or absent response (57.9%–100%)	No correlation between the vestibular areflexia and the cerebellar impairment (ICARS)	5, 12
SCA6	High-frequency aVOR	vHIT or MSC	aVOR gains were increased in the mild cases and decreased in the severe cases (MSC)	aVOR gains (MSC) were negatively correlated with the severity of disease (ICARS)	1, 19, 20
			Very frequent aVOR Impairment of at least one SCC (vHIT, MSC)	aVOR gains (vHIT) for each canal showed a negative correlation with the severity of disease (SARA)
			Preferential impairment of PC aVOR gains (vHIT)	aVOR gains (vHIT) for the PCs with CS in the PCs were significantly lower than the aVOR gains with no CS
				The differences in the head impulse aVOR gains (vHIT) were larger between the ACs and PCs in those with^a) perverted HITs than in those without
	Low- to intermediate-frequency aVOR	RCT, caloric test	Normal to increased aVOR gain regardless of the disease severity (RCT, caloric test)	No correlation between the aVOR gain and clinical parameters (RCT, caloric test)	14, 20
	Low- to intermediate-frequency aVOR	RCT, caloric test	Normal aVOR gain (100%, RCT)		14, 20
	Linear VOR	Linear acceleration of the whole body along the interaural axis (MSC)	Normal LVOR latency, but decreased sensitivity. Catch-up saccades were generated	Not available	23
FRDA	High-frequency aVOR	vHIT or MSC	Prolonged aVOR latency and decreased aVOR gain for all SCCs (MSC)	HC gain reduction and the prolonged aVOR latency correlated with increased horizontal saccadic latency (MSC)	8, 26
		vHIT or MSC	Decreased aVOR gain (100%), prolonged aVOR latency, abnormal CS (vHIT)		8, 26
		Clinical HIT	Abnormal HIT (54.8%)	Abnormal HIT is more frequently observed in patients with longer disease duration and in patients with higher FARS, ICARS, and SARA scores	28
	Low- to intermediate-frequency aVOR	EVAR	Significantly lower mean time constant than in healthy controls	Time constant of EVAR responses decreased with the duration of the disease	28
	Low- to intermediate-frequency aVOR	Caloric test	Reduced aVOR gain (41%)	Not available	29
CANVAS	High-frequency aVOR	vHIT or MSC	Decreased aVOR gain (100%) for all SCCs with abnormal CS (MSC, vHIT)	Negative correlation between the aVOR gain and disease duration (vHIT)	36, 41, 42, 46
	High-frequency aVOR	vHIT or MSC	Decreased VVOR gain (MSC, vHIT)		36, 41, 42, 46
	Low- to intermediate-frequency aVOR	RCT, Caloric test	Absent or severely reduced horizontal nystagmus responses (100%, RCT, caloric test)	Not available	42

Disease subtype	Presumed responsible anatomical structures	Type of VOR impairment (central/peripheral/mixed)	Reference
SCA3	Medial vestibular nucleus, nucleus prepositus hypoglossi, possible involvement of primary vestibular afferents	Central±peripheral	1, 5, 7, 14, 16
SCA6	Flocculus, paraflocculus (vestibulo-cerebellum)	Central	1, 19, 20
FRDA	Vestibular nuclei, vestibular nerve, spiral ganglion	Mixed (central+peripheral)	26, 28, 30, 32, 34
CANVAS	Vestibular (Scarpa’s) ganglion, cerebellar vermis	Mixed (peripheral+central)	42, 46, 48

Table 1. Summary of VOR findings in key subtypes of hereditary cerebellar ataxia

Perverted HIT was defined as the eyes moved upward in addition to horizontally, producing a “cross-coupled” VOR during the horizontal head impulse.

Table 2. Presumed anatomical origin and type of VOR impairment in hereditary cerebellar ataxias

VOR, vestibulo-ocular reflex; SCA3, spinocerebellar ataxia type 3; SCA6, spinocerebellar ataxia type 6; FRDA, Friedreich Ataxia, CANVAS, cerebellar ataxia neuropathy vestibular areflexia syndrome.

The anatomical origin is presumed based on current clinical, neurophysiological, and pathological evidence, and may vary depending on individual cases.