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The Role of Central Vestibular Dysfunction in Cognitive and Physical Impairment in Ambulatory Multiple Sclerosis

Published online by Cambridge University Press:  02 January 2026

Özge Özdemir Open the ORCID record for Özge Özdemir [Opens in a new window] ,
İsa Tuncay Batuk ,
Ayla Fil Balkan ,
Pınar Acar Özen ,
Aslı Tuncer  and
Yeliz Salcı
Özge Özdemir*
Affiliation:
Faculty of Physical Therapy and Rehabilitation, Hacettepe University, Ankara, Turkey Department of Physiotherapy, Vocational School of Health Services, Avrasya University, Trabzon, Turkey
İsa Tuncay Batuk
Affiliation:
Department of Audiology, Faculty of Health Sciences, Hacettepe University, Ankara, Turkey
Ayla Fil Balkan
Affiliation:
Faculty of Physical Therapy and Rehabilitation, Hacettepe University, Ankara, Turkey
Pınar Acar Özen
Affiliation:
Neurology Department, School of Medicine, Hacettepe University, Ankara, Turkey
Aslı Tuncer
Affiliation:
Neurology Department, School of Medicine, Hacettepe University, Ankara, Turkey
Yeliz Salcı
Affiliation:
Faculty of Physical Therapy and Rehabilitation, Hacettepe University, Ankara, Turkey
*
Corresponding author: Özge Özdemir; Email: ozgeozdemir0907@gmail.com
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Abstract

Background:

The aim of this study was to investigate the effects of central vestibular dysfunction on physical functionality and cognitive function in individuals with multiple sclerosis (MS).

Methods:

Fifty-two fully ambulatory individuals with MS (Expanded Disability Status Scale [EDSS] ≤ 4) were included and divided into two groups: those with central vestibular involvement (Group 1; n = 25) and those without (Group 2; n = 27). Central vestibular involvement was assessed using videonystagmography. Physical and cognitive functions were evaluated in all participants using the Glittre Activities of Daily Living (ADL) test, Godin Leisure-Time Exercise Questionnaire (GLTEQ), and the physical dimension of the MSQoL-54 for physical functionality, and the BICAMS, Trail Making Test (TMT), Word List Generation test and the cognitive dimension of the MSQoL-54 for cognitive function.

Results:

According to the physical functionality assessment results, the time required to complete the Glittre ADL test was longer in group 1 than in group 2 (p = 0.01). The score for the physical dimension of the MSQoL-54 was lower in group 1 (p = 0.045). In the BICAMS Symbol Digit Modalities Test, Group 1 scored lower than Group 2 (p = 0.013). A significant difference between the groups was also observed in the time taken to complete the TMT (p = 0.017). Additionally, Group 1 exhibited lower scores on the cognitive dimension of the MSQoL-54 (p = 0.012).

Conclusion:

Physical functionality and specific cognitive domains differed between MS participants with and without central vestibular involvement. It should be considered that vestibular dysfunction may adversely impact cognitive and physical functionality, even in low-moderate disability level.

Résumé

RÉSUMÉ

Le rôle du dysfonctionnement vestibulaire d’origine centrale dans les troubles cognitifs et physiques chez les personnes ambulatoires, atteintes de sclérose en plaques.

Contexte :

L’étude visait à examiner les effets du dysfonctionnement vestibulaire d’origine centrale sur le fonctionnement physique et cognitif chez les personnes atteintes de sclérose en plaques (SP).

Méthodes :

Au total, 52 personnes atteintes de SP mais pleinement ambulatoires (échelle étendue d’incapacité de Kurtzke ([EDSS] ≤ 4) ont participé à l’étude; elles ont été divisées en deux groupes : celles qui présentaient une atteinte vestibulaire centrale (groupe 1; n = 25) et celles qui en étaient exemptes (groupe 2; n = 27). L’atteinte vestibulaire centrale a été évaluée par nystagmographie vidéo; il y a eu une évaluation du fonctionnement physique et cognitif chez tous les participants à l’aide des tests suivants : le test Glittre Activities of Daily Living (ADL), le Questionnaire sur les habitudes d’activité physique de loisir de Godin (GLTEQ), la partie sur l’état physique du questionnaire MSQoL 54 pour le fonctionnement physique, le BICAMS, le test des tracés (TMT), le test de la génération de listes de mots (WLG) et le volet cognitif du MSQoL 54 pour le fonctionnement cognitif.

Résultats :

Compte tenu des résultats de l’évaluation du fonctionnement physique, le temps nécessaire pour réaliser le test Glittre ADL était plus long dans le groupe 1 que dans le groupe 2 (p = 0,01). Le score relatif au volet physique du MSQoL 54 était plus faible dans le groupe 1 (p = 0,045) que dans l’autre. Quant au test Symbol Digit Modalities du BICAM, le groupe 1 a obtenu des résultats plus faibles que le groupe 2 (p = 0,013). De plus, un écart important a été relevé entre les deux groupes en ce qui concerne le temps nécessaire pour effectuer le TMT (p = 0,017). Enfin, le groupe 1 a moins bien réussi que le groupe 2 au volet cognitif du MSQoL 54 (p = 0,012).

Conclusion :

Il ressort de l’étude des différences dans le fonctionnement physique et dans certains domaines cognitifs entre les sujets souffrant ou non d’une atteinte vestibulaire centrale. Il faudrait donc considérer que le dysfonctionnement vestibulaire peut altérer le fonctionnement cognitif et physique, même chez les personnes présentant un degré faible ou modéré d’incapacité.

Keywords

multiple sclerosisvestibular dysfunctioncognitive functionphysical functionalityvideonystagmography

Information

Type
Original Article
Information
Canadian Journal of Neurological Sciences , First View , pp. 1 - 8
Copyright
© The Author(s), 2026. Published by Cambridge University Press on behalf of Canadian Neurological Sciences Federation

Highlights

  • Central vestibular involvement in MS is linked to physical and non-spatial cognitive deficits.

  • Vestibular impairments remain clinically relevant in ambulatory MS and are not fully captured by EDSS.

  • Head-eye coordination and postural stability are key contributors to daily functional capacity in MS.

Introduction

Multiple sclerosis (MS) is a central nervous system (CNS) disorder characterized by both autoimmune and neurodegenerative processes, with its etiology remaining unknown. Reference Lassmann1 Neurological symptoms vary according to CNS involvement, with common involvement of the optic nerve, pyramidal tract, cerebrum, sensory pathways, cerebellum and vestibular system. Reference Romano, Caltagirone and Nocentini2

The vestibular system, which perceives movement and verticality, provides sensory input to regulate balance and align the eyes, head and body. It also plays a key role in cognitive functions like spatial memory, orientation and navigation. Reference Maihoub, Molnár, Tamás and Szirmai3,Reference Dieterich and Brandt4 Vestibular involvement in MS can occur early and may be peripheral, central or both. Reference Zeigelboim, Arruda and Mangabeira-Albernaz5–Reference Gür, Binkhamis and Kluk8

Previous studies have documented problems associated with vestibular dysfunction in individuals with MS, including impaired gaze stabilization, dizziness and difficulties with postural control. Reference Mañago, Schenkman, Berliner and Hebert9,Reference Cochrane, Christy and Motl10 Among these, postural control problems are the most extensively studied, affecting 80% of MS participants, with 36–56% of these deficits attributed to vestibular dysfunction. Reference Zeigelboim, Arruda and Mangabeira-Albernaz5 Although cognitive impairment is associated with vestibular dysfunction, Reference Smith, Zheng, Horii and Darlington11,Reference Smith12 this relationship in the MS population has not been sufficiently investigated.

Only one study has investigated central vestibular dysfunction and cognition in MS, reporting a correlation between reduced vestibulo-ocular reflex (VOR) gain and cognitive impairment, which suggests overlapping neurological pathways. Reference Cochrane, Christy, Sandroff and Motl13 However, that study did not evaluate all cognitive domains, and their control group consisted of healthy individuals. To the best of our knowledge, no other research has compared the cognitive status of participants with and without central vestibular dysfunction.

Beyond identifying deficits associated with central vestibular dysfunction, its impact on physical functionality – including ambulation, manual dexterity, axial control and activities of daily living (ADL) – needs to be demonstrated. Reference Taylor, Whittington and Hollingsworth14 However, few studies have investigated the impact of central vestibular dysfunction on physical functionality. Reference Cochrane, Christy and Motl10–Reference Tacchino, Skjerbæk and Podda15

This study primarily aims to investigate cognitive function across all domains related to central vestibular dysfunction and secondarily to assess its effect on physical functionality.

Methods

Participants

This cross-sectional study was conducted at Hacettepe University between October 2022 and April 2024. Approval was granted by the Hacettepe University Non-Interventional Clinical Research Ethics Committee (approval number GO; 22/856). The inclusion criteria were as follows: a diagnosis of MS based on the 2017 McDonald criteria, no relapse in the past 3 months, an Expanded Disability Status Scale (EDSS) score of ≤ 4 and an age range of 18 to 55 years. The upper age limit was set at 55 to account for the potential influence of age-related vestibular degeneration. The inclusion threshold of EDSS ≤ 4.0 was selected to ensure that all participants were fully ambulatory and capable of independently completing the physical functionality assessments, particularly the Glittre ADL test. This cut-off also minimized potential confounding effects of higher disability, fatigue and compensatory strategies on physical and cognitive performance.

Exclusion criteria comprised the presence of peripheral vestibular dysfunction, as well as any additional disease that could interfere with the assessments. In addition, medical records were carefully reviewed to ensure that individuals with any additional neurological, psychiatric or systemic disorders that could interfere with cognitive or vestibular assessments – such as major depressive disorder, anxiety disorders or other comorbid conditions – were excluded from participation.

A total of 85 individuals diagnosed with MS were initially screened for eligibility. Of these, 52 participants who met the inclusion criteria and provided informed consent were enrolled in the study. All participants were fully informed about the study objectives and procedures, and written informed consent was obtained prior to data collection.

Based on the results of videonystagmography (VNG), 25 MS participants with central vestibular dysfunction and 27 MS participants without any vestibular dysfunction were enrolled in our study (Figure 1).

Figure 1.

Flow chart of study.

Outcome measures

All assessments were conducted in a quiet environment over three consecutive days. Vestibular system evaluations were performed on the first day, physical function assessments on the second and cognitive function tests on the third day. To minimize the potential impact of accumulating physical and cognitive fatigue, all measurements were conducted during morning hours.

The evaluation process commenced with the collection of demographic data, including age, sex and body mass index, as well as disease-specific characteristics. Participants meeting the inclusion criteria were divided into two groups based on the results of the VNG test battery: those with central vestibular involvement (Group 1, n = 25) and those without vestibular involvement (Group 2, n = 27).

Subjective assessments of vestibular function were conducted using the Vertigo Symptom Scale (VSS) and the Dizziness Handicap Inventory (DHI). Physical functionality was assessed through the Glittre ADL test, the Godin Leisure-Time Exercise Questionnaire and the physical component of the Multiple Sclerosis Quality of Life-54 (MSQoL-54) scale. Cognitive functions were evaluated using the Brief International Cognitive Assessment for MS (BICAMS) battery, the Trail Making Test (TMT), the Word List Generation (WLG) test and the cognitive component of the MSQoL-54.

Vestibular system assessment

Positional tests

In this study, positional tests were conducted to evaluate peripheral vestibular dysfunction, which served as an exclusion criterion. Three participants diagnosed with peripheral vestibular dysfunction were excluded from the study.

Dix-Hallpike Test. This positional test is used to diagnose posterior canal benign paroxysmal positional vertigo, particularly right-sided canalolithiasis. The participant is rapidly moved from sitting to a supine position with the head turned 45° toward the affected side and extended slightly below horizontal. A positive test elicits torsional nystagmus toward the affected ear, whereas its absence indicates a negative result. Reference Imai and Inohara16 ,Reference Boselli, Kleiser, Bockisch, Hegemann and Obrist17

Supine Roll Test. The test is performed with the participant lying supine, with the head flexed at 30°. The head is quickly turned 90° to each side in the horizontal plane, and the affected side is determined by comparing the direction and intensity of the elicited nystagmus. Reference You, Instrum and Parnes18

VNG test battery

A VNG system (Video ENG, Micromedical Technologies INC) was used to evaluate central vestibular involvement. This computerized, noninvasive and objective system assesses VOR pathway function by recording eye movements in response to visual stimuli via video goggles. Reference Moideen, Konkimalla and Tyagi19 ,Reference Ni, Kim, Nair, Bien, Yu and Foyt20 VNG provides guidance for distinguishing central vestibular pathologies. Reference Cochrane, Christy and Motl7–Reference Wu, Luo and Chen21

Central dysfunction was identified by pathological findings in at least two oculomotor tests (pursuit, saccade, optokinetic) and nystagmus not suppressed by fixation or occurring in any direction. Assessments were conducted by an audiologist (T.B) in a quiet room. Before testing, goggles were calibrated. Participants sat ∼ 1 m from the screen. They were advised to avoid caffeine, non-prescription drugs and eye makeup for 12 hours prior.

Gaze Test. The participant was instructed to follow a visual target that appeared on the screen in various directions, using only their eyes while keeping their head still. The evaluation was completed both along the midline and in different gaze directions at 30° angles (up, down, left, right). During the spontaneous nystagmus assessment, the participant was asked to focus on a fixed point. The spontaneous nystagmus test was performed using Frenzel goggles. The gaze test results were noted as either the presence or absence of nystagmus. Reference Zuniga and Adams22

Pursuit Test. In this test, the visual target displayed on the screen moves slowly from left to right. The participant is instructed to follow the moving target with their eyes. The participant’s pursuit ability is assessed at three different frequencies: 0.1, 0.2 and 0.4 Hz. Although pursuit gain can vary with age, a gain of above 0.8 is generally considered normal. Reference Abasi, Hoseinabadi, Raji, Friedman and Hadian23

Saccade Test. A visual target disappears and reappears at a different location, and the participant is expected to follow it. Velocity, accuracy and latency are analyzed; speeds below 430°/s are considered abnormal. Both hypometric and hypermetric saccades are pathological. Reference Abasi, Hoseinabadi, Raji, Friedman and Hadian23

Optokinetic Test. The participant tracked a target moving right and left on the horizontal axis at 30°/s with a 4 Hz frequency, covering about 87% of the visual field. Reference Cao, Zhu and Zhou24 Asymmetry in gain between right and left gaze was examined for both eyes. Gain, the key parameter in optokinetic testing, indicates central vestibular lesions when abnormal. The practitioner recorded the degree of gain asymmetry. Reference Wu, Luo and Chen21

Head Shake Test. The participant moves their head ∼ 30° right and left at 2 Hz for 20–25 repetitions. Nystagmus occurring 1–2 s after movement ends is considered pathological, and its presence or absence is recorded. Reference Hain, Fetter and Zee25

Vertigo Symptom Scale (VSS)

The VSS-short form was used in the subjective evaluation of the vestibular system. It is a subjective questionnaire that measures the individual’s vertigo, dizziness and autonomic anxiety over the last month. Reference Kondo, Kiyomizu and Goto26 The 15-item short form used in this study yields a total score ranging from 0 to 60, with scores of 12 or above indicating clinical significance. Reference Wilhelmsen, Strand, Nordahl, Eide and Ljunggren27

Dizziness Handicap Inventory (DHI)

The DHI is a 25-item self-report questionnaire that assesses dizziness and its impact on quality of life. Reference Kondo, Kiyomizu and Goto26 The maximum score from the survey is 100. Sixty points or above indicate severe dizziness. Reference Zamyslowska-Szmytke, Politanski and Jozefowicz-Korczynska28

Assessment of physical functionality

Glittre ADL test

The Glittre ADL test, validated for ambulatory MS participants, Reference Kaya, Köse and Salcı29 assessed functional capacity and daily activity performance. It was conducted on a 10 m track with a chair, two-step staircase and shelves at different heights. Participants wore a backpack (2.5 kg for women, 5 kg for men) and moved 1 kg objects between shelves across five laps, with total time recorded. Blood pressure, heart rate, oxygen saturation, dyspnea and fatigue were measured before and after the test using a sphygmomanometer, pulse oximeter and modified Borg scale. To minimize learning effects, the researcher first demonstrated the test, followed by one practice lap before the actual evaluation. Reference Reis, Karloh, Fonseca, Biscaro, Mazo and Mayer30

Godin Leisure-Time Exercise Questionnaire (GLTEQ)

Physical activity levels over the past week were assessed using the GLTEQ, which categorizes exercise as mild, moderate or strenuous. Activities performed for over 15 minutes in the previous 7 days were recorded, and their frequencies were multiplied by metabolic equivalents (3 for mild, 5 for moderate and 9 for strenuous) to calculate the physical activity score. Reference Sari and Erdoğan31

MSQoL-54 physical score

The MSQoL-54 consists of 12 subheadings and 54 questions. Two types of scores are obtained: physical and cognitive health status averages. Topics covered by the physical assessment are fatigue, physical functionality, health perceptions, pain, sexual functions and energy. High scores are considered to indicate good physical condition. Reference Vickrey, Hays, Harooni, Myers and Ellison32

Assessment of cognitive functions

BICAMS

The BICAMS battery consists of the Symbol Digit Modalities Test (SDMT) and the immediate recall trials of the California Verbal Learning Test–II (CVLT-II) and the Brief Visuospatial Memory Test–Revised (BVMT-R). The SDMT evaluates working memory, processing speed and attention by matching symbols to numbers in 90 s. In our study, the oral version of the SDMT was used. The CVLT-II assesses auditory verbal learning through recall of 16 words over five repetitions. The BVMT-R measures visuospatial memory by having participants draw six symbols from memory after viewing them for 10 s, repeated across three trials. Each figure is scored 0–2 based on accuracy and position, with a maximum of 12 points per trial and a total score summed over all trials. Reference Ozakbas, Yigit, Cinar, Limoncu, Kahraman and Kösehasanoğulları33

Trail Making Test (TMT)

TMT was used to assess executive functions. Participants were asked to connect numbers and letters in sequence as quickly and accurately as possible. Completion times were recorded. Reference Kabiri, Jameie and Balali34

Word List Generation (WLG) Test

The WLG test was used to assess verbal fluency. Participants were asked to spontaneously generate words from a specific category within 60 s, while the researcher recorded their responses. Repeated words were excluded from the total. Reference Prosperini, Castelli, De Luca, Fabiano, Ferrante and De Giglio35

MSQoL-54 cognitive score

In addition to the physical subscale, the MSQoL-54 includes a cognitive function subscale, which assesses emotional state, social and cognitive skills. Higher scores indicate better cognitive health, while lower scores suggest poorer cognitive health. Reference Vickrey, Hays, Harooni, Myers and Ellison32

Statistical analyses

All statistical analyses were conducted using IBM SPSS v.26.0 software. Normality was assessed using the Shapiro–Wilk test. For normally distributed variables, the independent samples t-test was applied, whereas the Mann–Whitney U test was used for non-normally distributed variables. Numerical data are presented as mean ± standard deviation (X±SD). A p-value of <0.05 was considered statistically significant. Multivariate analysis of covariance (MANCOVA) was performed to examine between-group differences in physical and cognitive domains, with baseline scores of the dependent variables, age and EDSS included as covariates. Subsequent univariate ANCOVA analyses were conducted to evaluate differences for each test individually, and Bonferroni correction was applied. Post-hoc power analyses for the SDMT revealed a large effect size (Cohen’s d = 0.85; Cohen’s f = 0.425) with an observed power of approximately 85%, indicating that the sample size was sufficient to detect significant differences.

Results

A total of 52 participants with MS were included in the study: 25 with central vestibular involvement (Group 1) and 27 without vestibular involvement (Group 2). The groups were comparable in terms of age, sex, disease duration, BMI and EDSS scores (p > 0.05) (Table 1). Four participants in Group 1 had an EDSS score of 4, with mean cerebellar FSS of 1.5 ± 0.58 and brainstem FSS of 2.5 ± 0.32. In Group 2, three participants had an EDSS of 4.0, with mean cerebellar FSS of 1.33 ± 0.42 and brainstem FSS scores of 0.

Table 1.

Demographics and physical characteristics of participants

Note: Group-1: Those with central vestibular involvement, Group-2: Those without vestibular involvement, x Student-T Test, y Mann Whitney U Test, k Pearson Chi-Square Test, BMI = body mass index, EDSS = Expanded Disability Status Scale, F = female, M = male, X ± SD = mean ± standard deviation, *significant p-value, p<0.05.

Vestibular system assessment

VNG results revealed the most pronounced abnormalities in saccade and optokinetic tests in Group 1. No vertical or horizontal gaze abnormalities were observed in Group 2 (Table 2).

Table 2.

Number of abnormal findings in parameters evaluated for VNG testing

Note: Group-1: Those with central vestibular involvement, Group-2: Those without vestibular involvement. VNG = videonystagmography.

When the gaze nystagmus test averages for the groups were examined, significant differences were found in the following measures: pursuit at 0.1 Hz, pursuit at 0.4 Hz, latency for left gaze, latency for right gaze and optokinetic responses for both left and right gaze (p = 0.046, p = 0.010, p = 0.005, p = 0.003, p < 0.001, p < 0.001, respectively). However, no significant differences were observed in the pursuit at 0.2 Hz and in the accuracy of left and right gaze (p > 0.05) (Table 3).

Table 3.

Comparison of videonystagmography test averages and vestibular function scores of the groups

Note: Group-1: Those with central vestibular involvement, Group-2: Those without vestibular involvement, X ± SD: Mean±Standard Deviation, aStudent-T Test, bMann Whitney U Test, *significant p-value, p<0.05.

Assessment of physical functionality

According to the MANCOVA results, a significant group difference was observed in the physical functioning domain (Wilks’ Λ = 0.745, F (2,49) = 8.38, p = 0.001, η2 = 0.26) (Table 4). Follow-up univariate ANCOVA analyses, controlling for age and EDSS, indicated that Group 2 performed significantly better on the Glittre ADL test (F(1,49) = 18.54, p = 0.002, η2 = 0.27) (Table 5). In addition, MSQoL-Physical scores were significantly higher in Group 2 compared with Group 1 (F(1,49) = 5.92, p = 0.015, η2 = 0.11) (Table 5). By contrast, no significant group differences were found in GLTEQ scores (p = 0.593) (Table 5).

Table 4.

Multivariate analysis of covariance (MANCOVA) results for physical and cognitive domains

Note: Multivariate analysis of covariance (MANCOVA) was performed with baseline scores of each dependent variable, age, and EDSS entered as covariates. A p value <0.05 was considered statistically significant. ADL = Activities of Daily Living; GLTEQ = Godin Leisure-Time Exercise Questionnaire; MSQoL = Multiple Sclerosis Quality of Life; SDMT = Symbol Digit Modalities Test; TMT = Trail Making Test; WLG = Word List Generation; CVLT-II = California Verbal Learning Test–II; BVMT-R = Brief Visuospatial Memory Test–Revised.

Table 5.

Univariate ANCOVA results for physical and cognitive tests (domain-specific Bonferroni correction, controlling for age and EDSS)

Note: Univariate ANCOVA was conducted controlling for age and EDSS. Bonferroni corrections were applied within each domain: Physical (2 tests, α = 0.025), MSQoL-Physical (1 test, α = 0.05), Processing speed/Executive (4 tests, α = 0.0125), Memory (2 tests, α = 0.025) and MSQoL-Cognitive (1 test, α = 0.05). P values below the domain-specific corrected α were considered statistically significant. ADL = Activities of Daily Living; GLTEQ = Godin Leisure-Time Exercise Questionnaire; MSQoL = Multiple Sclerosis Quality of Life; SDMT = Symbol Digit Modalities Test; TMT = Trail Making Test; WLG = Word List Generation; CVLT-II = California Verbal Learning Test–II; BVMT-R = Brief Visuospatial Memory Test–Revised.

Assessment of cognitive functions

Group 1 scored 34.40 ± 12.54 on the SDMT, 51.92 ± 20.78 on TMT-A and 92.60 ± 47.47 on TMT-B, while Group 2 scored 43.81 ± 13.71, 42.00 ± 15.29 and 69.14 ± 28.18, respectively (all p < 0.05). No significant differences were observed in WLG, CVLT-II, or BVMT-R scores. MSQoL-Cognitive scores were higher in Group 2 (71.48 ± 16.98) than in Group 1 (58.51 ± 20.37, p = 0.012) (Table 5).

In the cognitive domain, MANCOVA revealed significant group differences in processing speed, executive function and verbal fluency (Wilks’ Λ = 0.672, F (4,46) = 7.82, p = 0.001, η2 = 0.40) (Table 4). Follow-up univariate ANCOVA analyses confirmed that Group 2 outperformed Group 1 on the SDMT (p = 0.008), TMT-A (p = 0.011), and TMT-B (p = 0.004) tests (Table 5). MANCOVA results were not significant for memory tests (p = 0.13) (Table 4), and neither CVLT-II nor BVMT-R scores differed significantly between groups (p > 0.05) (Table 5). MSQoL-Cognitive scores were significantly higher in Group 2 (F(1,50) = 6.65, p = 0.012, η2 = 0.12) (Table 4 and Table 5).

Discussion

The main finding of this study is that individuals with MS and central vestibular involvement exhibited lower cognitive and physical performance compared with those without such involvement. Physical functionality, including functional capacity and activities of daily living, is also negatively affected. These results suggest that central vestibular dysfunction significantly impacts both cognitive and physical aspects of quality of life. Due to the heterogeneous CNS involvement in MS, attributing clinical findings to a single symptom is challenging. Thus, analyzing cognitive and physical parameters without controlling for confounders is methodologically inappropriate. Comparing MS participants with and without vestibular involvement is more valid than using healthy controls. To improve specificity, we included only fully ambulatory individuals with EDSS ≤ 4.

Studies in the literature evaluating the vestibular system in individuals with MS predominantly focus on the peripheral vestibular component. Reference Cochrane, Christy and Motl7–Reference Ulozienė, Totilienė and Balnytė36 The detection of central vestibular dysfunction in MS is particularly challenging due to factors such as limited access to advanced imaging technologies, the widespread occurrence of peripheral vestibular disorders in the general population and the specialized knowledge needed to reliably detect central vestibulopathies. Reference Ulozienė, Totilienė and Balnytė36 We utilized the VNG test battery, which is considered both sensitive and reliable in the literature for the assessment of central vestibular dysfunction. Our findings indicate that the VNG test results reveal that the most common abnormalities in individuals with central vestibular involvement are head shake nystagmus and pursuit tests. This result indicates that individuals are affected by rapid head movements and have a decreased ability to perform smooth pursuit.

Few studies have examined central vestibular assessment in individuals with MS. One study explored its relationship with walking capacity in those with an EDSS below 6.5. Reference Cochrane, Christy and Motl10 In this correlation study, central vestibular integration was evaluated using reflexive VOR gain, VOR cancelation and subjective visual vertical (SVV) variance. Walking capacity was strongly correlated with VOR cancelation and SVV variance, but not with reflexive VOR gain. Although our methodology differed from Cochrane’s, our findings are consistent: individuals with central vestibular involvement show reduced walking and functional capacity compared to those without.

Tacchino et al. also demonstrated that the vestibular and visual systems are related to walking capacity in individuals with MS who have an EDSS score of 3,4. Reference Tacchino, Skjerbæk and Podda15 Recent studies have highlighted the vestibular system’s impact on lower extremities in MS. However, vestibular insufficiency may also affect the trunk and upper limbs, contributing to overall physical dysfunction. Reference Cusin, Tomaz, Ganança, Oliveira, Gonçalves and Caovilla37 Therefore, we used the Glittre ADL test to assess both walking and upper limb function. In our study, test completion time was longer in the group with central vestibular involvement, while pre-test fatigue levels were similar between groups. These results indicate that central vestibular involvement impairs not only walking but also overall physical function in individuals with MS.

In addition to the Glittre ADL Test, the GLTEQ and the physical component of the MSQoL-54 were used to assess physical functionality. The MSQoL-54 results showed significantly lower scores in the group with central vestibular involvement, supporting its negative impact on physical function. The decline in the physical component, consistent with the Glittre-ADL test results, suggests significant limitations in activities of daily living. Despite similar GLTEQ scores between groups, accessibility and financial constraints may have influenced the results, as many activities in the questionnaire require specific facilities and costs.

Only a single study has investigated the effects of central vestibular dysfunction on cognition in individuals with MS, which involved 40 participants with MS and 20 healthy controls. Reference Cochrane, Christy, Sandroff and Motl13 Using the rotating-chair test to evaluate vestibular function and the BICAMS battery for cognitive assessment, the authors reported a moderate correlation between reduced VOR gain and cognitive impairment. Previous research in individuals with peripheral vestibular failure has documented visuospatial deficits in cases of unilateral or bilateral vestibular loss. Reference Popp, Wulff, Finke, Rühl, Brandt and Dieterich38 In contrast, our study did not find evidence of such visuospatial impairments in participants with central vestibular involvement. The absence of significant group differences on the BVMT-R may be explained by the test’s focus on visual–spatial memory alone, without assessing more complex spatial skills such as orientation and navigation, which are particularly vulnerable to vestibular dysfunction. Reference Day and Reynolds39 Therefore, future research should incorporate assessments targeting advanced spatial abilities, including spatial orientation and real-world navigation tasks.

SDMT is known to involve rapid and repetitive saccadic eye movements. Reference Pavisian, Patel and Feinstein40 Thus, the reduced performance observed in MS individuals with central vestibular dysfunction may partly reflect oculomotor impairments. However, we argue that this decline is not solely due to motor dysfunction but is more likely attributable to reduced cognitive processing speed and attentional deficits. Although the SDMT requires visual scanning and motor responses, it is widely recognized as a reliable indicator of cognitive processing speed and attention in individuals with MS. Reference Costa, Genova, DeLuca and Chiaravalloti41 Therefore, the observed decline in performance cannot be fully explained by impaired saccadic eye movements alone. Moreover, similar performance reductions in other cognitive measures within the central vestibular dysfunction group support the notion that central vestibular dysfunction may be associated with broader, multidimensional cognitive impairments.

In interpreting the reduced SDMT and Trails performance observed in the group with central vestibular involvement, potential confounding effects of isolated oculomotor abnormalities were considered. However, participants were classified as having central vestibular dysfunction only if at least two oculomotor tests were pathological, and individuals with isolated nystagmus or any ophthalmologic disorder were excluded. Therefore, it is unlikely that the observed cognitive differences were solely due to eye movement disturbances; rather, they reflect a broader cognitive impact associated with central vestibular processing.

A study involving a 12-week vestibular training program for individuals with MS, which reported a mean EDSS score of 2.8 (as stated in the original study, although EDSS is an ordinal scale), demonstrated improvements across all subtests of the BICAMS. Reference Darwish, El-Tamawy, Ismail, Moustafa and Khalifa42 However, the presence of vestibular impairment among the MS participants in the study was not assessed, which constitutes a limitation. Despite this, the findings of the study lend support to the association we have established between the vestibular system and cognitive functions in MS.

In addition to the BICAMS battery, our study evaluated broader cognitive domains. Executive functions, assessed via the TMT, revealed significant between-group differences. Specifically, both TMT-A and TMT-B completion times differed significantly, suggesting that central vestibular involvement may influence not only basic cognitive-motor processing speed but also higher-order executive functions.

In this study, the cognitive subscale of the MSQoL-54 was utilized to assess self-perceived cognitive functioning. Participants with central vestibular involvement reported significantly lower cognitive scores compared to those without. This reduction reflects greater cognitive difficulties in daily life and suggests that vestibular dysfunction may substantially impact the cognitive dimension of quality of life in individuals with MS.

When looking at the relationship between the vestibular system and cognition in the healthy population, vestibular dysfunction is thought to lead to atrophy in areas within the cortical vestibular network, including the hippocampus. It is also thought that this atrophy may affect cognitive parameters such as visual–spatial ability, executive functions, attention and working memory. Reference Bigelow and Agrawal43 However, this conclusion is a general interpretation of vestibular dysfunction. Reference Kremmyda, Hüfner and Flanagin44 In our study examining the specific effect of central vestibular involvement in MS participants, we found that the working memory, information processing speed, attention and executive functions of the groups were affected. The fact that both groups in our study consisted of individuals with MS allowed us to exclude possible effects of the disease on cognition.

This study has several limitations. Functional MRI was not used to confirm structural or functional changes in the cortical vestibular network. The inclusion of neuroimaging could have provided deeper insights into the neural basis of cognitive impairments. Additionally, a specific depression scale was not used in this study. However, participants with diagnosed psychiatric disorders, including depression, were excluded under the additional disease criterion, and none were receiving active psychiatric treatment. Furthermore, the emotional items within the MSQoL-54 provided an indirect indication of mood status. Future studies incorporating validated mood scales may offer a more detailed understanding of the interaction between vestibular dysfunction, depression and cognition. In addition, although post-hoc power analysis indicated a large effect size and adequate statistical power for key outcomes, the relatively small and carefully selected sample may restrict the generalizability of the findings. Future multicenter studies with larger and more diverse MS cohorts are needed to confirm these results.

Conclusion

Our findings demonstrated that, despite comparable EDSS scores, individuals with central vestibular involvement exhibited impairments in both physical functioning and non-spatial cognitive domains. These results highlight the critical role of vestibular functions – such as head–eye coordination coordination and postural stability – even in participants with minimal disability. Future rehabilitation strategies that specifically target vestibular function may yield benefits across both cognitive and physical domains.

Acknowledgements

None.

Author contributions

  • Ö.Ö. and Y.S.: Conceptualization

  • Ö.Ö., İ.T.B., Y.S., A.F.B.: Methodology

  • Ö.Ö. and Y.S.: Formal analysis and investigation

  • Ö.Ö. and Y.S.: Writing

  • P.A.Ö. and A.T.: Resources

Funding statement

This research received no specific grant from any funding agency, commercial or not-for-profit sectors.

Competing interests

This manuscript has not been published elsewhere and is not under consideration by any other journal. The authors declare that there are no conflicts of interest.

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Figure 0

Figure 1. Flow chart of study.

Figure 1

Table 1. Demographics and physical characteristics of participants

Figure 2

Table 2. Number of abnormal findings in parameters evaluated for VNG testing

Figure 3

Table 3. Comparison of videonystagmography test averages and vestibular function scores of the groups

Figure 4

Table 4. Multivariate analysis of covariance (MANCOVA) results for physical and cognitive domains

Figure 5

Table 5. Univariate ANCOVA results for physical and cognitive tests (domain-specific Bonferroni correction, controlling for age and EDSS)