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Review Article
Oculomotor manifestations in inflammatory central nervous system demyelinating diseases: a narrative review
Eun-Jae Leeorcid
Research in Vestibular Science 2025;24(1):27-36.
DOI: https://doi.org/10.21790/rvs.2024.022
Published online: March 14, 2025

Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Corresponding author: Eun-Jae Lee Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea. E-mail: eunjae.lee@amc.seoul.kr
• Received: November 18, 2024   • Revised: February 1, 2025   • Accepted: February 27, 2025

© 2025 The Korean Balance Society

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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  • Inflammatory central nervous system (CNS) demyelinating diseases are a group of disorders in which inflammation within the CNS damages the myelin sheath, a protective and conductive layer surrounding nerve fiber in the brain and spinal cord, leading to various neurological symptoms. Common conditions include multiple sclerosis and neuromyelitis optica spectrum disorders, both characterized by relapses and progressive deterioration over time. Given their frequent involvement of the brainstem and cerebellum, these diseases often manifest with oculomotor findings, such as ocular misalignment and instability, providing valuable insights into lesion localization within specific anatomical regions. Recent studies suggest that these findings may also indicate broader pathological burdens, including potential cortical damage, positioning them as potential early biomarkers for disease progression. This review explores oculomotor findings in patients with CNS demyelinating diseases, examining their characteristics, underlying mechanisms, and clinical significance. It also highlights the potential role of these findings as disease biomarkers.
  • Keywords: Multiple sclerosis; Neuromyelitis optica; Demyelinating diseases; Eye movements; Eye manifestation
Neurons communicate through electrical signals, and preserving these signals during axonal transmission is essential for sustaining brain function [1]. Myelin, an insulating layer produced by oligodendrocytes in the central nervous system (CNS), surrounds neuron axons to ensure fast and efficient signal conduction [2]. When demyelination occurs, electrical signals slow or weaken, leading to brain dysfunction and a range of neurological symptoms [3].
Inflammatory CNS demyelinating diseases are typically driven by autoimmune processes that attack myelin, causing inflammation and demyelination [3]. Among these conditions, multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are well-known [4]. In MS, immune-mediated damage targets the myelin sheath and oligodendrocytes, although the specific antigen that triggers this response remains unknown [5]. In NMOSD, autoantibodies specifically target the aquaporin-4 (AQP4) protein on astrocytes, leading to astrocyte damage and subsequent demyelination [6,7]. Despite these distinct mechanisms, both diseases are marked by relapses and progressive decline, requiring precise and personalized long-term care.
Looking into eyes can be instrumental in the care of CNS demyelinating diseases. While optic neuritis, a classic example of afferent visual system involvement, is among the most frequent relapse manifestations, patients with CNS demyelinating diseases also experience ocular motor disorders that lead to symptoms like diplopia and oscillopsia [8-12]. Historically, Jean-Martin Charcot, the founder of modern neurology [13], identified Charcot’s neurologic triad of nystagmus, intention tremor, and scanning or staccato speech [14], which are hallmark symptoms often associated with MS. Although these symptoms are not specific or pathognomonic to MS, oculomotor findings have been recognized in demyelinating diseases since the advent of modern diagnostic practices.
MS commonly affects the infratentorial regions (brainstem and cerebellum), areas critical in assessing dissemination in space [5,15], and NMOSD also frequently involves the brainstem near cerebrospinal fluid (CSF) linings, areas rich in AQP4 proteins [6,16]. These lesions may result in various oculomotor findings (Table 1). Recent advancements in techniques for tracking eye movements and vestibular function have highlighted the diagnostic and clinical value of oculomotor assessments in inflammatory CNS demyelinating diseases [12]. This review will explore oculomotor findings in patients with inflammatory CNS demyelinating diseases, focusing on their characteristics, underlying mechanisms, and clinical implications.
Multiple Sclerosis
MS is a chronic, inflammatory demyelinating disease, and its diagnosis requires the identification of lesions across both space and time [5]. The brainstem and cerebellum, as part of the infratentorial region, are key areas considered in the “space” criterion for MS, alongside other regions such as the periventricular area, juxtacortical region, and spinal cord. Consequently, evaluating the brainstem and cerebellum is essential in MS diagnosis, and oculomotor symptoms and signs play a significant role in this process.
Common ocular motor abnormalities include internuclear ophthalmoplegia (INO), saccadic hypermetria, gaze-evoked nystagmus (GEN), and impaired vestibulo-ocular reflex (VOR) suppression [17,18]. These abnormalities, often chronic, impair visual function and reduce quality of life, though they may also present during acute relapses [17,19,20]. Oculomotor findings in MS can be categorized into ocular misalignment, ocular instability, and asymptomatic ocular motor dysfunction [10]. Ocular misalignment may manifest as paralytic conditions, such as INO, or nonparalytic forms like skew deviation. Ocular instability includes symptoms such as nystagmus or saccadic intrusions. Asymptomatic ocular motor dysfunction refers to subtle neurologic abnormalities that are detectable during clinical examination, such as impaired inhibition of the VOR. Oculomotor manifestations vary depending on the locations of CNS lesions.

Findings in brainstem lesions

In the brainstem, demyelination and axonal damage of the medial longitudinal fasciculus (MLF), particularly within the midline tegmentum of the pons (ventral to the fourth ventricle) or midbrain (ventral to the cerebral aqueduct), leads to INO, the most common saccadic disorder in MS [21,22]. INO in MS may present as either an acute manifestation during an MS relapse or as a chronic condition [10]. Chronic INO typically arises from incomplete recovery following a prior attack or as a result of ongoing disease progression. Patients with chronic INO are often asymptomatic, though they may occasionally experience vague visual disturbances. MS is a significant cause of INO, accounting for 32% to 34% of all cases [23,24]. Up to 60% of INO cases in MS patients show recovery after at least 9 months [23].
INO is characterized by impaired adduction of the affected eye and horizontal jerk nystagmus of the contralateral eye during abduction. Although adduction during convergence is typically preserved, this dissociation may sometimes be absent. INO results from a lesion in MLF, which transmits adduction signals from the contralateral abducens nucleus to the ipsilateral oculomotor nucleus [21]. INO impairs binocular coordination. In some cases, the only sign of INO may be slowed adducting saccades (adduction lag), with full adduction range and no apparent nystagmus [25]. Eye movement recordings can aid in detecting this subtle manifestation [26]. On neurologic examination, dissociated nystagmus may be observed in the abducting eye, which consists of saccadic oscillations rather than true nystagmus [27]. Patients commonly report diplopia or, more subtly, blurred vision and visual confusion, especially during head movements or head-on-body rotations (e.g., walking or driving), due to transient disruptions in binocular fusion [28]. As MLF lesions are often small and may not be visible on magnetic resonance imaging (MRI), a thorough neurologic examination is critical for detection.
The MLF also carries information related to vertical, torsional, and velocity eye movements, originating from the utricle and vertical semicircular canals [26,29]. Thus, INO may be associated with skew deviation, a form of vertical strabismus characterized by hypertropia on the side of the lesion. Skew deviation is a nonparalytic vertical ocular misalignment that occurs in all gaze directions [30] and is typically caused by lesions in the central graviceptive vestibular pathways, including the cerebellum. Skew deviation is conventionally described by the side of the lower eye. When a lesion occurs below the decussation of vestibular pathways at the pontine level, the lower eye is on the side opposite the lesion. In MS, acute skew deviation often accompanies contralateral INO [31], while in the chronic phase, it reflects cerebellar involvement and may present as alternating skew deviation [32]. In some cases, the full ocular tilt reaction (OTR), which includes skew deviation, contralateral head tilt, and ocular torsion, can occur, reflecting dysfunction of vestibular responses in the roll plane [33]. The role of the MLF in conveying contralateral posterior semicircular canal signals is supported by studies combining MRI and video-head-impulse testing [34]. In unilateral INO, vertical diplopia may result from a subtle skew deviation. Skew deviation and OTR can also occur with lesions outside the MLF, such as those in the cerebellum or thalamus. Additionally, tilt of the subjective visual vertical, a misperception of verticality, is frequently observed in patients with MS [22]. In bilateral INO, impairment of the vertical VOR and smooth pursuit is often noted, as the MLF also transmits vestibular and smooth pursuit signals from the vestibular nuclei to midbrain nuclei involved in vertical gaze control. Convergence is typically spared, unless the MLF lesion is located at a higher level in the midbrain tegmentum.
Additional brainstem syndromes may occur in MS, including fascicular involvement of cranial nerves III, IV, or VI, with these syndromes occasionally presenting as the initial symptom [11]. Ocular motor cranial nerve palsies in MS are attributed to demyelination of the fascicular portion of the nerves within the brainstem and typically occur during clinical relapses. Among these, sixth nerve palsy is the most frequently observed, though it occurs in only 0.4% to 1% of MS patients during a relapse [35-37]. Third nerve palsy is less common, presenting as the initial sign in 2.8% of MS cases [38]. Partial third nerve involvement, often sparing or variably affecting the pupil, is more typical [39,40]. Meanwhile, fourth nerve palsy is rare in MS [41]. One-and-a-half syndrome is characterized by an ipsilateral INO and horizontal gaze palsy, leaving only contralateral abduction intact, while convergence is preserved. This syndrome results from a lesion in the MLF and either the ipsilateral abducens (VI) nucleus (nuclear type) or the paramedian pontine reticular formation (supranuclear type). In nuclear lesions, all eye movements are impaired, whereas supranuclear lesions spare reflexive eye movements, such as those elicited by oculocephalic maneuvers. When accompanied by ipsilateral facial nerve palsy, the presentation is referred to as eight-and-a-half syndrome. MS accounts for approximately 30% of one-and-a-half syndrome cases, typically during acute relapses [40,42]. Recovery is often partial, with residual INO persisting in many patients. Horizontal nuclear or supranuclear gaze palsies, without INO, have also been reported in MS [43,44]. Dorsal midbrain syndromes may also present with a range of saccadic gaze abnormalities, including upward or downward gaze palsies, convergence-retraction nystagmus, and impaired convergence [11,45]. Additionally, MS patients may experience acute central vestibular syndromes, often due to the involvement of brainstem structures beyond the intrapontine eighth nerve fascicle, such as the medulla, cerebellar peduncles, posterior pontine tegmentum, and midbrain [46].
Ocular instability can also occur in MS, with GEN being the most common [17,47]. GEN is characterized by a fast-phase movement in the direction of eccentric gaze, which is horizontal during lateral gaze and vertical during upward gaze. It involves a slow centripetal drift of the eyes from an eccentric position, followed by a corrective quick phase. This phenomenon results from dysfunction in the gaze-holding neural integrator, also known as the velocity-to-position integrator [29]. In horizontal gaze, the integrator relies on the nucleus prepositus hypoglossi (NPH) and medial vestibular nuclei (MVN), while vertical gaze depends on the superior vestibular nuclei, MLF, and midbrain interstitial nucleus of Cajal [48]. The system is further regulated by feedback from the cerebellar flocculus and paraflocculus, which are connected to the brainstem network. Consequently, lesions in the brainstem, cerebellum, or both can disrupt this system, leading to GEN. Patients with GEN are rarely symptomatic, and it typically reflects chronic disease rather than acute relapse.
Primary position nystagmus can also arise from brainstem lesions, with upbeat nystagmus linked to focal damage in the caudal medulla or pontine tegmentum [10,49]. Acquired pendular nystagmus (APN), characterized by rhythmic, slow-phase oscillations, is occasionally observed in MS [50]. When present, APN exhibits small amplitude, high frequency, and remarkable regularity, often leading to disabling oscillopsia in primary gaze. Proposed mechanisms include delays in the ocular motor feedback loop affecting velocity-to-position integrators that stabilize gaze [51] or from abnormal visual feedback due to optic nerve pathology [52,53]. Accordingly, APN frequently associates with chronic optic neuropathy or diffuse pontine tegmental lesions [10]. While poor vision and delayed visual input from demyelinated pathways (e.g., after optic neuritis) may contribute to APN, the high-frequency oscillations that characterize the condition remain unchanged in darkness, suggesting that APN originates within the brainstem-cerebellar neural integrator network [54]. The resetting of APN oscillations by large saccades [51], which cause a phase shift, also supports this hypothesis. Accordingly, MS patients with APN often show lesions in the paramedian pons in the region of the paramedian tract cell groups, part of the neural integrator loop, which would consequently lose normal feedback [18]. See-saw nystagmus, marked by alternating upward and inward rotation of one eye and downward and outward rotation of the other, is usually linked to parasellar, chiasmal, or midbrain lesions, and also has occasionally been reported in patients with MS [55,56].

Findings in cerebellar lesions

The cerebellum and its connections are commonly affected by tissue damage in MS, often resulting in ocular instability [8-12]. The pattern of cerebellar dysfunction can be correlated with lesion topography, enabling the identification of syndromes involving specific regions such as the flocculus/paraflocculus, nodulus/uvula, and dorsal vermis/fastigial nuclei.
Lesions involving the flocculus and paraflocculus, regions of the vestibulocerebellum, typically lead to impaired smooth pursuit and an inability to suppress the horizontal VOR during combined eye-head tracking [57]. GEN and downbeat nystagmus are also commonly observed in MS. GEN is thought to arise from defects in the neural integrator network, which includes cerebellar structures [58]. Downbeat nystagmus, marked by spontaneous vertical eye oscillations with upward slow phases, is thought to arise from the loss of inhibitory control from the cerebellum on the vertical semicircular canals [59].
Lesions of the nodulus and uvula have been linked to positional nystagmus, downbeat nystagmus, and periodic alternating nystagmus (PAN). Central positional nystagmus, either downbeat or upbeat, which presents as positional vertigo, is associated with demyelinating lesions in the superior cerebellar peduncle [60] and results from disruption of central otolithic connections between deep cerebellar structures and the vestibular nuclei. PAN, which involves spontaneous horizontal jerk nystagmus that reverses direction every 2 minutes, is a well-established disorder of the velocity storage mechanism in the vestibular system and has been linked to demyelination of central vestibular pathways at the cerebellar peduncles [9].
Involvement of the dorsal vermis and fastigial nuclei typically causes saccadic dysmetria and impaired smooth pursuit, presenting as “saccadic” on clinical examination. Saccadic dysmetria is one of the most common chronic ocular movement abnormalities in MS [22], which is present in approximately 30% to 40% of patients with MS [17,47]. Dysmetric saccades, which may be hypermetric (overshooting the target) or hypometric (undershooting the target), are associated with lesions of the fastigial nuclei and dorsal vermis, respectively. When one fastigial nucleus is affected, the resulting lesions have a functional bilateral impact, leading to bilateral saccadic hypermetria. APN, which causes significant visual disability, may also be caused by cerebellar lesions.

Miscellaneous findings in brainstem/cerebellar lesions

Patients with MS may experience disabling oscillopsia caused by various forms of eye oscillations, including saccadic intrusions and oscillations with differing amplitudes, such as square-wave jerks, macro square-wave jerks, and macrosaccadic oscillations. The most common saccadic intrusions in MS are square-wave jerks and macro square-wave jerks, frequently linked to cerebellar syndrome [61]. Ocular flutter (horizontal) and opsoclonus (multidirectional) are usually associated with paraneoplastic syndromes or post-viral infections but can occasionally be caused by MS [62]. These saccadic oscillations may appear during relapse or, in the case of ocular flutter, persist in chronic forms [63,64]. Saccadic intrusions or oscillations with a short intersaccadic interval (200–400 milliseconds) typically result from impaired cerebellar feedback on saccadic control, whereas those without an intersaccadic interval (e.g., ocular flutter or opsoclonus) are associated with instability in brainstem networks, often due to altered membrane properties of burst neurons [65-67].
The examination of eye movements, focusing on the dynamic properties of saccades, smooth pursuit, and visual inhibition of the VOR, can provide further critical insights into chronic brainstem and cerebellar disorders. These findings may be subtle but provide crucial information for diagnosis and management. Key findings include adduction saccade slowing in INO and saccadic hypermetria (see above). In MS patients, smooth pursuit evaluation is also essential. However, saccadic or jerky pursuit is nonspecific, as it can occur in individuals who are fatigued, visually impaired, uncooperative, or taking sedative medications [62]. The smooth pursuit network spans multiple regions, and its impairment lacks topographic specificity, limiting the diagnostic value of smooth pursuit testing. In contrast, assessing VOR inhibition through fixation is more effective for identifying dysfunctions in the smooth pursuit/fixation system. While smooth pursuit deficits can result from lesions in the cerebellum, brainstem, or cerebral hemispheres, impaired VOR inhibition is more specifically associated with chronic cerebellar dysfunction, particularly diffuse lesions in the vestibulo-cerebellum [68].

Dysfunction in higher-order control networks

Oculomotor abnormalities can arise from cortical lesions that disrupt the higher-order control network for eye movements. Among the methods used to evaluate this network, the antisaccade task is the most common ocular motor test for assessing cognitive control. This task challenges individuals to suppress an automatic saccade toward a visual stimulus and instead generate a saccade of equal amplitude in the opposite direction. A simplified version of this test can even be performed at the bedside [69]. The dorsolateral prefrontal cortex (PFC) is central to this process, playing a key role in inhibiting reflexive saccades that would otherwise be triggered by the parietal eye fields. In MS patients, deficits in this control network are evident—they make more errors during the antisaccade task and exhibit prolonged saccadic latencies compared to controls [70,71]. These impairments are increasingly linked to cerebellar dysfunction, emphasizing the cerebellum's role in cognitive regulation [72].
Difficulties are not limited to antisaccades. Memory-guided saccades, which require directing saccades toward remembered targets, also present challenges for MS patients. Inaccurate saccades, particularly during tasks requiring the execution of memorized target sequences, suggest underlying working memory deficits [73]. Furthermore, MS patients often display hypometric saccades to predictable targets and increased latencies when responding to random visual targets accompanied by distractors [74]. These abnormalities collectively highlight an impaired ability to maintain inhibitory control, pointing to dysfunction within the PFC and its connections to thalamocorticostriatal circuits [75].
Neuromyelitis Optica Spectrum Disorders
NMOSD is an inflammatory demyelinating disease of the CNS caused by anti-AQP4-antibodies (AQP4-Ab) [6]. AQP4, an essential water channel protein, is primarily expressed in ventricular ependymal cells at the brain-CSF barrier, subependymal glia, the glia limitans, and astrocytic end-feet at the blood-brain barrier [76]. The neural circuits governing ocular movements are located near the fourth ventricle and cerebral aqueduct, regions frequently impacted by NMOSD-related lesions [77]. This anatomical proximity accounts for the wide range of oculomotor symptoms observed in NMOSD, including disruptions in eye movement and vestibular function.

Findings

Due to the rarity of NMOSD, studies exploring its oculomotor manifestations are limited. In a study of 90 NMOSD patients, comprehensive ocular motor examinations revealed eye movement abnormalities in 38% and quantitative saccadic test abnormalities in 67% [78]. The most common findings included GEN (25.6%), upbeat or downbeat nystagmus (9.3%), saccadic abnormalities (18.9%), impaired smooth pursuit (16.7%), INO (13.3%), skew deviation (11.1%), and VOR abnormalities (7.8%).
Other studies in NMOSD patients have also reported a range of ocular motor disturbances, such as convergence-retraction nystagmus [79], downbeat nystagmus [79], upbeat nystagmus [80], and opsoclonus [80]. Additionally, the anatomical proximity of the vestibular nuclear complex to the area postrema, regions frequently affected in NMOSD, likely accounts for the observation that approximately 25% of patients with intractable nausea, vomiting, and hiccups also exhibit nystagmus [81].

Distinct features in neuromyelitis optica spectrum disorder and multiple sclerosis

Oculomotor findings can aid in distinguishing NMOSD from MS, as the diseases affect different neural structures. MS primarily involves areas adjacent to the lateral ventricles, inferior temporal lobe, and curved U-fibers [82], whereas NMOSD frequently targets regions near the third and fourth ventricles with high AQP4 expression [83]. A single-center study comparing 42 MS and 26 NMOSD patients highlighted these differences, showing that horizontal GEN was more prevalent in NMOSD. Additionally, patients with NMOSD exhibited a higher likelihood of bilateral lesions in the MVN and NPH at the pontomedullary junction, adjacent to the fourth ventricle. These findings align with the predilection of NMOSD for brainstem structures, contributing to horizontal GEN and rebound nystagmus. These findings are remarkable in that differentiating NMOSD from MS is critical, as their treatments differ significantly, and MS disease-modifying therapies can exacerbate NMOSD [83-85]. While AQP4-Ab testing has greatly improved diagnostic accuracy [3], 10% to 50% of NMOSD patients may still test negative, even with sensitive assays [86,87]. Furthermore, around 20% of NMOSD patients present with brain lesions without optic nerve or spinal cord involvement [88]. Oculomotor features may offer valuable diagnostic insights in such cases, especially when serological results are inconclusive.
Perspective: Oculomotor Findings as Biomarkers
Oculomotor findings, particularly eye movement abnormalities such as INO and saccadic impairments are gaining recognition as valuable biomarkers in CNS demyelinating diseases like MS [11]. These abnormalities provide insight into the underlying demyelination and axonal damage in key pathways, including the MLF, and are strongly associated with disease severity, cognitive dysfunction, and imaging metrics such as lesion load and gray matter atrophy. INO, as a model of impaired neural conduction, has been instrumental in studying fatigue and temperature sensitivity in MS [89], while its precise characterization using advanced techniques like diffusion tensor imaging underscores its potential as a composite marker of axonal and myelin integrity [90,91].
The double-step saccadic test has been suggested as a promising tool for quantifying oculomotor dysfunction in MS [92]. By assessing rapid eye movements toward two successive targets, this test captures the structural and functional disruptions in cortical and subcortical networks governing saccades. Double-step saccadic metrics, including the proportion of correct responses and saccadic errors, are significantly impaired in MS and correlate with cognitive deficits, physical disability, and MRI findings of gray matter atrophy and lesion burden. These metrics outperformed other saccadic tasks in their relationship with clinical and imaging outcomes, highlighting their robustness as potential biomarkers [92].
By integrating oculomotor assessments like INO evaluation and double-step saccadic tests, clinicians and researchers can better monitor disease progression, assess treatment efficacy, and explore novel therapeutic targets, especially in remyelination trials. This approach underscores the need for further validation and longitudinal studies to fully harness the potential of these biomarkers in CNS demyelinating diseases.
Patients with CNS demyelinating diseases frequently exhibit oculomotor findings that reflect the anatomical localization of lesions, with distinct patterns depending on the underlying pathogenesis of conditions like MS and NMOSD. Emerging evidence highlights the potential of these oculomotor manifestations as biomarkers for monitoring disease progression and predicting prognosis, particularly in assessing brain lesion burden and myelin integrity. These findings underscore the need for larger, long-term studies to validate their clinical utility and expand their role in guiding therapeutic strategies.

Funding/Support

None.

Conflicts of Interest

No potential conflict of interest relevant to this article was reported.

Availability of Data and Materials

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

Table 1.
Oculomotor findings in central nervous system demyelinating diseases
Syndrome Localization Clinical findings
Ocular misalignment
 INO MLF lesion Reduced adduction velocity to the ipsilateral side
 Skew MLF or cerebellar lesion Vertical misalignment, diplopia
 One-and-a-half syndrome Ipsilateral MLF lesion with PPRF and/or VI nucleus lesion INO with horizontal gaze palsy
 Abducens nerve palsy Abducens (VI) nerve fascicle lesion Abduction palsy or paresis
 Dorsal midbrain syndrome Dorsal midbrain lesion Vertical gaze palsy, impaired convergence, convergence-retraction nystagmus, light-near dissociation
Ocular instability
 Gaze-evoked nystagmus Gaze-holding neural-integrator lesion (cerebellar or brainstem lesion) Horizontal nystagmus directed toward the side of eccentric gaze
 Pendular nystagmus Disruption in feedback pathwaysa) Back-and-forth slow-phase ocular oscillations without quick saccades
 Periodic alternating nystagmus Cerebellar lesion (nodulus and uvula, cerebellar peduncle) Nystagmus alternating direction periodically, separated by brief null intervals
 Saccadic intrusion/oscillations Cerebellar lesion, brainstem lesion (pause neurons) Square-wave jerks, ocular flutter, opsoclonus
 Saccadic dysmetria Cerebellar lesion (fastigial nucleus, dorsal vermis) Overshoots or undershoots of saccades
 Lack of VOR inhibition Cerebellar lesion (flocculus or paraflocculus) Inability to suppress the VOR

INO, internuclear ophthalmoplegia; MLF, medial longitudinal fasciculus; PPRF, paramedian pontine reticular formation; VOR, vestibulo-ocular reflex.

a)Ocular motor feedback loop affecting velocity-to-position integrators or visual feedback from the optic nerve.

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        Oculomotor manifestations in inflammatory central nervous system demyelinating diseases: a narrative review
        Res Vestib Sci. 2025;24(1):27-36.   Published online March 14, 2025
        DOI: https://doi.org/10.21790/rvs.2024.022
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      Oculomotor manifestations in inflammatory central nervous system demyelinating diseases: a narrative review
      Oculomotor manifestations in inflammatory central nervous system demyelinating diseases: a narrative review
      Syndrome Localization Clinical findings
      Ocular misalignment
       INO MLF lesion Reduced adduction velocity to the ipsilateral side
       Skew MLF or cerebellar lesion Vertical misalignment, diplopia
       One-and-a-half syndrome Ipsilateral MLF lesion with PPRF and/or VI nucleus lesion INO with horizontal gaze palsy
       Abducens nerve palsy Abducens (VI) nerve fascicle lesion Abduction palsy or paresis
       Dorsal midbrain syndrome Dorsal midbrain lesion Vertical gaze palsy, impaired convergence, convergence-retraction nystagmus, light-near dissociation
      Ocular instability
       Gaze-evoked nystagmus Gaze-holding neural-integrator lesion (cerebellar or brainstem lesion) Horizontal nystagmus directed toward the side of eccentric gaze
       Pendular nystagmus Disruption in feedback pathwaysa) Back-and-forth slow-phase ocular oscillations without quick saccades
       Periodic alternating nystagmus Cerebellar lesion (nodulus and uvula, cerebellar peduncle) Nystagmus alternating direction periodically, separated by brief null intervals
       Saccadic intrusion/oscillations Cerebellar lesion, brainstem lesion (pause neurons) Square-wave jerks, ocular flutter, opsoclonus
       Saccadic dysmetria Cerebellar lesion (fastigial nucleus, dorsal vermis) Overshoots or undershoots of saccades
       Lack of VOR inhibition Cerebellar lesion (flocculus or paraflocculus) Inability to suppress the VOR
      Table 1. Oculomotor findings in central nervous system demyelinating diseases

      INO, internuclear ophthalmoplegia; MLF, medial longitudinal fasciculus; PPRF, paramedian pontine reticular formation; VOR, vestibulo-ocular reflex.

      Ocular motor feedback loop affecting velocity-to-position integrators or visual feedback from the optic nerve.

      Table 1.

      Res Vestib Sci : Research in Vestibular Science
      © Korean Balance Society.
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