Abstract
Background
Oculomotor dysfunction is common in multiple sclerosis (MS), yet central positional nystagmus (CPN) remains insufficiently characterised. As a manifestation of central vestibular pathway dysfunction, CPN may reflect subtle brainstem or cerebellar involvement. This study aimed to evaluate the occurrence and characteristics of CPN in MS using videonystagmography (VNG).
Methods
In this observational cross-sectional study, 46 patients with definite MS (Expanded Disability Status Scale [EDSS] ≤ 6.5) and 46 age- and sex-matched healthy controls underwent standardised positional testing (Dix–Hallpike, Pagnini–McClure, and Yacovino manoeuvres) recorded with VNG. MS patients were stratified by EDSS severity. Positional nystagmus was assessed for occurrence, direction, temporal pattern, canal-plane concordance, latency, and slow-phase velocity. Group differences were analysed using multivariable logistic regression adjusted for age and sex.
Results
Positional nystagmus was identified in 24/46 MS patients (52%) compared with 5/46 controls (11%). MS patients had significantly higher odds of exhibiting positional nystagmus than controls (odds ratio 9.06, 95% confidence interval 3.22–30.2; p < 0.001). Increased occurrence was observed across all positional manoeuvres. No significant differences were detected across EDSS severity strata, and age and sex were not significant predictors. Compared with controls, positional nystagmus in MS showed greater heterogeneity, higher slow-phase velocity, broader directional patterns, frequent canal-plane non-concordance.
Conclusions
CPN was commonly observed in this MS cohort. These findings support the feasibility of VNG-based positional testing in MS and suggest that CPN may reflect subtle infratentorial dysfunction, although its clinical relevance remains uncertain. Longitudinal studies integrating clinical and imaging data are warranted.
Keywords: Nystagmus, Multiple sclerosis, Central positional nystagmus, Oculomotor dysfunction, Videonystagmography
Background
Oculomotor dysfunction is a well-recognised manifestation of multiple sclerosis (MS) and has been explored as an indicator of structural and functional involvement across different stages of the disease [1]. Within this spectrum, central positional nystagmus (CPN) represents a comparatively under-studied phenomenon. CPN consists of involuntary rhythmic eye movements provoked by changes in head or body position and reflects disturbance within central vestibular pathways [2, 3]. Earlier estimates suggested a prevalence of approximately 6% in MS [4]. MS frequently affects infratentorial regions, including the brainstem and cerebellum. In this context, revisiting CPN using videonystagmographic (VNG) methods may help clarify whether it offers supplementary insight into subtle brainstem or cerebellar dysfunction in MS.
CPN has been associated with altered central processing of semicircular canal and otolith inputs, including potential involvement of the velocity-storage mechanism (VSM) [5]. Dysfunction of the cerebellar nodulus and uvula has been linked to certain patterns of positional nystagmus, particularly downbeat or apogeotropic forms, although the precise mechanisms underlying other variants—such as upbeating or geotropic nystagmus—are not fully established [5, 6]. Persistent apogeotropic responses have been interpreted in some studies as reflecting misestimation of the gravity vector [6], while cerebellar tonsillar involvement has been proposed as a possible contributor in selected geotropic presentations [7]. Deviations of the nystagmus vector from the expected axis of rotation may also arise from an imbalance between burst-generator and neural-integrator signals influenced by otolithic input [8].
Although quantitative oculomotor assessments such as saccadic eye movements and smooth pursuit have been investigated as markers of neuroanatomical involvement [9–14], data on CPN remain limited. Given the growing recognition of central vestibular disorders and vestibular involvement across a wide spectrum of neurological diseases, further systematic evaluation of positional nystagmus may help expand the existing evidence base and contribute to improved diagnostic and pathophysiological understanding.
Patients and methods
The study was approved by the Ethics Committee of Jessenius Faculty of Medicine, Comenius University in Bratislava, and written informed consent was obtained from all participants. Patients with definite MS according to the 2017 McDonald criteria, aged 18–55 years, and with Expanded Disability Status Scale (EDSS) scores ≤ 6.5 were recruited from the MS Centre, University Hospital Martin. All patients were clinically stable at the time of testing, with no relapse or corticosteroid treatment within the preceding three months. Exclusion criteria comprised other central or peripheral vestibular disorders (e.g. vestibular migraine, vestibulopathy) based on clinical and VNG tests,, contraindications to positional testing, and the use of substances or medications affecting oculomotor functions or recent infections.
A control group of 46 healthy participants was recruited, matched to MS patients for age (± 5 years) and sex. Control subjects had no history of MS, other CNS disorders, or known peripheral or central vestibular disease, and none had contraindications to positional testing (see Fig. 1).
Fig. 1.
Patient Flow Diagram for Participant Inclusion and Assessment Protocol
Clinical disability in MS patients was evaluated by a neurologist certified in EDSS scoring. The MS cohort (n = 46) was stratified into three subgroups according to EDSS: MS1: EDSS ≤ 1.5 (n = 19), MS2: EDSS > 1.5 to ≤ 4.0 (n = 16), MS3: EDSS > 4.0 to ≤ 6.5 (n = 11). Distribution of patients across EDSS severity levels is presented in Fig. 2.
Fig. 2.
Distribution of patients across EDSS severity levels in the MS cohort
Positioning testing protocol
Nystagmus was recorded using the SYNAPSYS VNG ULMER system with monocular infrared video goggles. All patients underwent a comprehensive oculomotor and vestibular examination, including clinical and VNG assessment of spontaneous nystagmus, gaze-evoked nystagmus, smooth pursuit, prosaccades, and stance and gait. Positioning testing was performed afterwards. After initial detection and eyeball alignment, geometric camera calibration was performed. All participants received standardized instructions prior to testing.
To assess positional nystagmus, three established maneuvers were applied: the Dix–Hallpike maneuver (posterior semicircular canals), the Pagnini–McClure supine roll test (horizontal canals), and the head-hanging test (Yacovino maneuver) (anterior canals).
In each position, the presence of positional nystagmus was evaluated. Positional nystagmus was defined using the mean of at least three consecutive nystagmoid jerks within 5 s. Parameters recorded included latency, duration, direction, amplitude, and waveform clarity sufficient for reliable identification on VNG. Each position was maintained for a minimum of one minute. Nystagmus was defined as reproducible if observed in at least two independent measurements and resistant to repositioning maneuvers.
Nystagmus classification criteria
Nystagmus was classified according to the framework of Lemos et al. (2022) [5]. The duration was categorized as paroxysmal when lasting less than one minute, and persistent when lasting one minute or longer. Another observable pattern is the paroxysmal-persistent form, characterised by an initial burst of nystagmus followed by a reduction in intensity after a few seconds. Concordance with the stimulated semicircular canal was evaluated by determining whether the observed nystagmus was aligned with the anatomical plane of the canal being tested (canal-plane concordant) or deviated from it (non-concordant). The direction of nystagmus was defined relative to head position: vertical forms were described as upward-beating (fast phase directed toward the forehead) or downward-beating (toward the chin), while horizontal forms were further classified relative to gravity as geotropic (beating toward the ground) or apogeotropic (beating away from the ground). Cases presenting both vertical and horizontal components were described as diagonal. Torsional components could not be reliably measured with the available system and were therefore excluded from analysis.
Statistical analysis
The R programming language (version 4.4.2) was used for data analysis, along with the libraries listed in the References. Categorical variables were described by counts and percentages and visualised with mosaic plots to show interactions with another categorical variable (e.g., with positional nystagmus prevalence). Continuous variables were summarised by the median with lower and upper quartiles and visualised with boxplots. Baseline differences in age and sex between MS patients and healthy controls were assessed using the Wilcoxon rank-sum (Mann–Whitney U) test for age and the chi-square test for sex. Frequency analysis was performed using contingency tables: categorical variables were summarised as counts and row-percentages within each group and compared between MS patients and controls using Pearson’s chi-squared or Fisher’s exact test, as appropriate. To examine the association between positional nystagmus prevalence and multiple predictors (age, duration, MS group, MS type, etc.), a single multivariable logistic regression was fitted including all prespecified predictors. The odds ratios (ORs) from the model were reported along with 95% confidence intervals. For variables showing evidence of association, emmeans were used to obtain model-based adjusted probabilities.
Because EDSS is reported in half-point increments and some categories contained small numbers, EDSS was not analyzed as a multi-level factor. Instead, a three-level severity variable (MS_group) was derived and used in logistic models to improve stability. Odds ratios were therefore adjusted for EDSS severity via MS_group. Since EDSS is not defined for controls, raw EDSS values were excluded from models that combined cases and controls. Other clinical variables, such as MS type and disease duration, were not included in these models.
Results
Study cohort characteristics
A total of 46 patients diagnosed with MS were examined, comprising 25 women and 21 men. The median of age of the MS group was 39 years with upper and lower quartiles 32 and 45. Additionally, data were collected from 46 healthy controls, matched for sex and age (within ± 5 years) (see Table 1).
Table 1.
Characteristics of the study cohort
| Total (N = 92) | MS Group (N = 46) | Control Group (N = 46) | |
|---|---|---|---|
| Age, median (Q1, Q3)] | 38.0 (32.0–44.0) | 38.5 (32.0–45.0) | 37.5 (30.0–44.0) |
| Female | 50 | 25 | 25 |
| Male | 42 | 21 | 21 |
Occurrence of positional nystagmus
Positional nystagmus was identified in 24 of 46 MS patients (52%) during at least one positional maneuver (Dix–Hallpike, Pagnini–McClure, or Yacovino), compared with 5 of 46 controls (11%) (see Fig. 3; Table 2). Statistical tests did not show any significant differences in age or sex between participants with and without positional nystagmus (age: Wilcoxon rank-sum test p = 0.30; sex: chi-square test p = 0.40).
Fig. 3.
Mosaicplot of group and positional nystagmus
Table 2.
Occurrence of positional nystagmus in MS and control groups
| Positional Nystagmus Group | Negative (N = 63) | Positive (N = 29) | p < 0.001 |
|---|---|---|---|
| control (N = 46) | 41 (89%) | 5 (11%) | |
| case (N = 46) | 22 (48%) | 24 (52%) |
Values are n (% within group). P-value from Pearson’s chi-squared test.
The logistic model identified a significant difference in the odds of having positional nystagmus: MS patients had ~ 9-fold higher odds than healthy controls (OR = 9.06, 95% CI 3.22–30.2, p < 0.001), confirming a higher occurrence among MS patients. For context, the model based proportions were 0.52 in MS vs. 0.11 in controls—an absolute difference of ~ 41% points (≈ 41 more positives per 100 MS patients compared with controls). None of the other covariates in the model (age and sex) showed a statistically significant association with positional nystagmus.
Within MS subgroups, positional nystagmus occurred in 11/19 MS1 patients (58%), 7/16 MS2 patients (44%), and 6/11 MS3 patients (55%). No statistically significant differences were detected between EDSS subgroups (see Table 3).
Table 3.
Occurrence of positional nystagmus across MS subgroups
| Positional Nystagmus Group | Negative (N = 22) | Positive (N = 24) |
|---|---|---|
| MS1 (N = 19) | 8 | 11 |
| MS2 (N = 16) | 9 | 7 |
| MS3 (N = 11) | 5 | 6 |
Maneuver-specific analysis
Positional nystagmus was evaluated with the Dix–Hallpike, Pagnini–McClure, and Yacovino maneuvers. For each, multivariable logistic regression adjusted for age and sex was performed, with model-based adjusted probabilities estimated using emmeans.
In the Dix–Hallpike maneuver, positional nystagmus was observed on the right side in 17 MS patients (37%) and 3 controls (4.5%), and on the left side in 14 MS patients (30%) and 2 controls (4.3%) (see Table 4). Bilateral positive responses occurred in 11 MS patients (23.9%) and 2 controls (4,3%). Adjusted differences were ~ 30 and 26% points, respectively, corresponding to higher odds in MS (right OR 8.36, 95% CI 2.52–38.3, p = 0.002; left OR 9.55, 95% CI 2.44–63.7, p = 0.004).
Table 4.
Positional nystagmus in Dix-Hallpike maneuver in MS and control groups
| Dix-Hallpike Maneuver | Right p < 0.001 |
Left p < 0.001 |
Bilateral | |||
|---|---|---|---|---|---|---|
| Group | Negative (N = 72) | Positive (N = 20) | Negative (N = 76) | Positive (N = 16) | Negative (N = 79) | Positive (N = 13) |
| control (N = 46) | 43 | 3 | 44 | 2 | 1 [43]* | 2 |
| case (N = 46) | 29 | 17 | 32 | 14 | 9 [26]* | 11 |
Values are n (% within group). P-value from Fisher’s exact test. *Numbers in square brackets indicate patients with negative findings on both sides. The number before the brackets indicates patients with a positive finding on one side and a negative finding on the other
In the Pagnini–McClure maneuver, right-sided nystagmus was detected in 12 MS patients (26%) and 3 controls (6.5%), while left-sided responses were present in 14 MS patients (30%) and 4 controls (8.7%); bilateral response was positive in 8 MS patients (17,4%) and 3 controls (6,5%) (see Table 5). Adjusted differences were ~ 19 and 21% points, with higher odds in MS (right OR 4.98, 95% CI 1.44–23.2, p = 0.019; left OR 4.54, 95% CI 1.46–17.3, p = 0.014).
Table 5.
Positional nystagmus in Pagnini-McClure maneuver in MS and control groups
| Pagnini–McClure Maneuver | Right p = 0.022 |
Left p = 0.016 |
Bilateral | |||
|---|---|---|---|---|---|---|
| Group | Negative (N = 77) | Positive (N = 15) | Negative (N = 74) | Positive (N = 18) | Negative (N = 81) | Positive (N = 11) |
| control (N = 46) | 43 | 3 | 42 | 4 | 1 [42]* | 3 |
| case (N = 46) | 34 | 12 | 32 | 14 | 10 [28]* | 8 |
Values are n (% within group). P-value from Fisher’s exact test. *Numbers in square brackets indicate patients with negative findings on both sides. The number before the brackets indicates patients with a positive finding on one side and a negative finding on the other
In the Yacovino maneuver, 11/46 MS patients (24%) and 3/46 controls (6.5%) were positive (see Table 6), corresponding to an adjusted difference of ~ 16 points and increased odds in MS (OR 4.48, 95% CI 1.26–21.2, p = 0.031).
Table 6.
Positional nystagmus in Yacovino maneuver in MS and control groups
| Yacovino Maneuver Group | Negative (N = 78) | Positive (N = 14) | p = 0.039 |
|---|---|---|---|
| control (N = 46) | 43 | 3 | |
| case (N = 46) | 35 | 11 |
Values are n (% within group). P-value from Fisher’s exact test
Across all maneuvers, age and sex were not significant predictors, and no significant differences were observed between EDSS subgroups.
Qualitative analysis of positional nystagmus
Across maneuvers, latency and SPV values showed considerable variability. In the Dix–Hallpike maneuver, the mean latency was 5.1 s (SD ± 7.76; range 0–30 s) and the mean SPV was 5.62°/s (SD ± 4.04; range 1.2–16.28°/s). For the Pagnini–McClure test, the mean latency was 3.37 s (SD ± 6.53; range 0–28 s) with a mean SPV of 4.12°/s (SD ± 3.08; range 1.3–15.52°/s). In the Yacovino maneuver, the mean latency was 3.82 s (SD ± 8.87; range 0–28 s), and the mean SPV measured 3.65°/s (SD ± 1.64; range 1.0–6.0°/s).The average latency and intensity of positional nystagmus across different positions are shown in Fig. 4.
Fig. 4.
Boxplot graphs of mean Latency of Nystagmus per Position (left), mean SPV of Nystagmus per Posion (right)
Regarding directional patterns across maneuvers, the Dix–Hallpike test most commonly elicited an upbeat vertical nystagmus, followed by horizontal and diagonal components. In the Pagnini–McClure maneuver, the most frequent directions were apogeotropic horizontal nystagmus, upbeat vertical nystagmus, diagonal upward variants, and geotropic responses. In the Yacovino maneuver, the predominant patterns included upbeat vertical nystagmus, rightward horizontal nystagmus, diagonal downward components, and leftward horizontal nystagmus (see Figs. 5 and 6).
Fig. 5.
Overall Most Common Nystagmus Directions Across All Maneuvers
Fig. 6.
Counts of Nystagmus Directions Across Each Maneuver
The relationship between nystagmus direction and the stimulated semicircular canal is presented in Fig. 7, demonstrating a substantial proportion of canal-plane concordant as well as non-concordant responses. Temporal analysis revealed a predominance of the persistent form, with nystagmus lasting longer than 60 s in the test position (see Fig. 8).
Fig. 7.
Canal-plane Concordance of Nystagmus Direction with Stimulated Canals
Fig. 8.
Temporal Pattern of Central Positional Nystagmus in Different Stimulating Positions
Qualitative analysis of positional nystagmus in healthy controls
Positional nystagmus elicited during Dix–Hallpike testing was infrequent and of low intensity. Latency was short, with a mean of 3.2 s (SD 4.4 s, range 0–8 s). Slow-phase velocity (SPV) values were low, with a mean of 2.16°/s (SD 1.45°/s, range 0.81–4.3°/s). All observed responses were persistent (> 60 s) rather than paroxysmal. Regarding directional characteristics, the most common pattern consisted of vertical or diagonal vertical nystagmus, consistent with canal-concordant posterior canal activation during the Dix–Hallpike manoeuvre.
During Pagnini–McClure testing, positional nystagmus in healthy controls again showed low velocity and minimal latency. Latency was typically absent or very short, with a mean of 1.6 s (SD 3.7 s, range 0–10 s). SPV averaged 1.83°/s (SD 0.76°/s, range 0.4–2.9°/s). All responses were persistent (> 60 s). The predominant pattern was horizontal nystagmus, in keeping with canal-concordant horizontal canal activation during roll testing.
Positional nystagmus elicited by the Yacovino manoeuvre was uncommon but showed greater latency variability. Latency had a mean value of 9.3s (SD 10.1 s, range 0–20 s). SPV remained low, with a mean of 2.10°/s (SD 0.56°/s, range 1.6–2.7°/s). All observed responses were persistent (> 60 s). Directional pattern consisted of vertical nystagmus.
Discussion
The present study examined the occurrence and characteristics of positional nystagmus in patients with MS compared with healthy controls using systematic VNG assessment. CPN was highly prevalent in the MS cohort and occurred significantly more frequently than in healthy individuals. No associations were observed between CPN and demographic variables such as age or sex.
CPN was identified in approximately 52% of MS patients in at least one tested position, a substantially higher prevalence than previously reported, where rates generally range from 6 to 7% [4, 14], with acute-phase series describing prevalences of around 5%, predominantly upbeating [15]. This discrepancy is most plausibly explained by methodological heterogeneity across studies, including differences in examination protocols, VNG sensitivity, diagnostic thresholds, and criteria for interpretation. In addition, disease-related factors such as lesion distribution, clinical phase at assessment (relapse versus remission), and exposure to disease-modifying or symptomatic treatments may further contribute to variability in reported prevalence [16]. Taken together, these considerations suggest that the higher detection rate observed in the present study more likely reflects systematic identification of subclinical positional nystagmus rather than a qualitatively distinct pathophysiological process.
CPN was also observed in 11% of healthy controls, consistent with reports demonstrating positional nystagmus in a proportion of neurologically normal individuals, with prevalences reported as high as 70–88% [17, 18]. The wide range of prevalence reported in healthy populations is likely attributable to differences in inclusion criteria, comorbidities, and testing methodology, including the use of alternative vestibular paradigms. In the present study, positional nystagmus in healthy controls was generally low-grade, stereotyped, and stable, whereas MS patients exhibited more frequent and qualitatively complex responses. Although interpretation is limited by the small number of positive controls, these findings suggest qualitative differences between physiological positional nystagmus and CPN observed in MS.
Previous studies evaluating oculomotor function in MS have demonstrated associations between abnormalities in smooth pursuit, saccades, antisaccades, and vestibulo-ocular reflex gain and increasing disability measured by the EDSS [19–21]. In contrast, the present findings indicate that CPN may be observed across the full spectrum of EDSS scores, including in patients with relatively low disability. Given the limited sensitivity of the EDSS in early or mildly affected individuals [22], this observation suggests that CPN may be more closely related to focal infratentorial involvement than to global neurological disability. While vestibular and positional testing may therefore provide supplementary functional information, the additional clinical value of CPN assessment remains to be established.
VNG assessment may offer functional insight into brainstem dysfunction even in cases where infratentorial lesions are not clearly detectable on MRI [23]. Oculomotor abnormalities are well-established manifestations of MS-related demyelination [10], with internuclear ophthalmoplegia resulting from medial longitudinal fasciculus involvement representing a classical marker of disrupted brainstem circuitry [24]. In this context, CPN may reflect dysfunction within brainstem and vestibulocerebellar vestibular networks, which are commonly affected by MS plaques. Impairment of the velocity storage mechanism provides a plausible physiological substrate for the observed positional responses [25]; however, in the absence of direct structure–function correlations, this interpretation remains speculative and should be regarded as hypothesis-generating.
Qualitative analysis across positional manoeuvres demonstrated heterogeneous response patterns dominated by vertical nystagmus, most commonly upbeating and directed towards the forehead, frequently accompanied by horizontal components resulting in diagonal eye movements. Positional upbeating nystagmus has been associated with lesions involving ascending vertical vestibulo-ocular reflex pathways, including the ventral tegmental tract, superior vestibular nucleus, caudal medulla, and vertical neural integrators [26, 27]. Horizontal components observed during both Dix–Hallpike and Pagnini–McClure manoeuvres were often not aligned with the expected plane of canal stimulation, a feature consistent with impaired central vestibular integration and considered characteristic of a central origin [28]. Apogeotropic horizontal nystagmus occurred more frequently during the Pagnini–McClure manoeuvre and has been linked to otolith–vestibulocerebellar dysfunction involving the nodulus and uvula [29], whereas geotropic responses may reflect asymmetric integration within otolith–cerebellar circuits [30].
Temporal and intensity characteristics further supported a central mechanism. Consistent with prior reports, latency was absent or short in most cases [3, 31–33], compatible with rapid activation of central vestibular pathways rather than otoconial inertia as observed in benign paroxysmal positional vertigo (BPPV). Elevated slow-phase velocities and persistence beyond 60 s were common, with some responses showing paroxysmal–persistent patterns. Patients did not report subjective vertigo, and repositioning manoeuvres failed to suppress the nystagmus. Although atypical BPPV may occasionally mimic central patterns, the combination of these features supports a predominantly central origin [34].
The literature addressing qualitative characteristics of CPN in MS remains limited. Existing reviews describe only a small number of cases, often with incomplete documentation of positional responses [32]. Isolated case reports have described patterns such as positional downbeating nystagmus mimicking anterior-canal BPPV or other vertical nystagmus syndromes [4, 35]. In this context, the present study provides a more systematic descriptive characterisation of CPN in MS; however, confirmation and refinement of these observations will require further investigation.
This observational, cross-sectional design allows detailed descriptive analysis but precludes causal inference and longitudinal assessment. Technical limitations include the inability of the VNG system to capture torsional eye movements and the absence of systematic ancillary vestibular testing, such as video head impulse testing or calorimetry. In addition, positional nystagmus findings were not correlated with detailed clinical history, relapse localisation, or MRI-derived lesion characteristics, limiting structure–function interpretation. Although predefined inclusion and exclusion criteria were applied, selection bias cannot be excluded. Future longitudinal studies integrating comprehensive vestibular evaluation with clinical and imaging data will be essential to clarify the clinical relevance of CPN in MS.
Conclusion
In summary, in this study CPN was frequently observed in patients with MS when assessed using VNG-based positional testing and was characterised by greater heterogeneity, higher slow-phase velocity, and reduced canal-plane concordance compared with healthy controls, findings consistent with a central mechanism. CPN occurred across a broad range of neurological disability, including in patients with low EDSS scores, without a clear association with disease severity.
Although these observations suggest that CPN may reflect subtle dysfunction of brainstem or cerebellar vestibular pathways, its clinical significance remains unclear. In the absence of consistent associations with symptoms, disability, or imaging findings, CPN cannot currently be regarded as a diagnostic or prognostic marker. Accordingly, interpretation should remain cautious until correlations with clinical features, functional measures, and imaging findings are available.
Acknowledgements
LK, would like to sincerely thank Marián Grendár for valuable advice and insightful discussions that significantly contributed to this work.
Authors’ contributions
PS designed the study and collected and analyzed the data. LK a MG conducted statistical analysis. SS, EK and EK assited in data interpretation and revision.
Funding
The work was supported by Grant VEGA 01/0092/22.
Data availability
The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.
Declarations
Ethics approval and consent to participate
All procedures performed in this study involving human participants were conducted in accordance with the ethical standards of the institutional and/or national research committee, and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The Ethics Committee of the Jessenius Faculty of Medicine in Martin, Slovakia, approved the realization of the research project (Approval No. EK 32/2023) on June 28, 2023. Written and informed consent was obtained from all individual participants included in the study.
Consent for publication
All authors have read and approved the final manuscript. Written and informed consent was obtained from all individual participants included in the study.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.