The prevalence of internuclear ophthalmoparesis in a population-based cohort of individuals with multiple sclerosis.

BACKGROUND: Internuclear ophthalmoparesis (INO) occurs in 15-52% of individuals with multiple sclerosis (MS) and is reliably detected by infrared oculography. Methods for diagnosing INO with infrared oculography and the association between INO and MS characteristics need confirmation. We aimed to describe INO prevalence and the clinical characteristics of individuals with MS and INO in a population-based cohort of individuals with MS born in the year 1966 (Project Y). METHODS: Previously described thresholds for the versional dysconjugacy index (VDI), assessed with standardized infrared oculography, were used to detect INO in participants of project Y. Clinical characteristics, visual functioning and complaints were compared between individuals with MS with INO and individuals with MS without INO. RESULTS: Two-hundred-twenty individuals with MS and 110 healthy controls were included. VDI values exceeding the threshold for INO presented in 53 (24%) individuals with MS and 19 controls (13%). INO was associated with male sex, greater disability, worse cognition and worse arm function in individuals with MS. There was no association with disease duration, visual functioning or complaints. CONCLUSIONS: INO is prevalent among individuals with MS aged fifty-three and related to clinical characteristics of MS. INO was more frequently detected in healthy controls than previous studies, implying that oculography based diagnosis of INO requires further refinement.

Impaired saccadic eye movements in multiple sclerosis are related to altered functional connectivity of the oculomotor brain network.

BACKGROUND: Impaired eye movements in multiple sclerosis (MS) are common and could represent a non-invasive and accurate measure of (dys)functioning of interconnected areas within the complex brain network. The aim of this study was to test whether altered saccadic eye movements are related to changes in functional connectivity (FC) in patients with MS. METHODS: Cross-sectional eye movement (pro-saccades and anti-saccades) and magnetoencephalography (MEG) data from the Amsterdam MS cohort were included from 176 MS patients and 33 healthy controls. FC was calculated between all regions of the Brainnetome atlas in six conventional frequency bands. Cognitive function and disability were evaluated by previously validated measures. The relationships between saccadic parameters and both FC and clinical scores in MS patients were analysed using multivariate linear regression models. RESULTS: In MS pro- and anti-saccades were abnormal compared to healthy controls A relationship of saccadic eye movements was found with FC of the oculomotor network, which was stronger for regional than global FC. In general, abnormal eye movements were related to higher delta and theta FC but lower beta FC. Strongest associations were found for pro-saccadic latency and FC of the precuneus (beta band ß = -0.23, p = .006), peak velocity and FC of the parietal eye field (theta band ß = -0.25, p = .005) and gain and FC of the inferior frontal eye field (theta band ß = -0.25, p = .003). Pro-saccadic latency was also strongly associated with disability scores and cognitive dysfunction. CONCLUSIONS: Impaired saccadic eye movements were related to functional connectivity of the oculomotor network and clinical performance in MS. This study also showed that, in addition to global network connectivity, studying regional changes in MEG studies could yield stronger correlations.

Saccadic delay in multiple sclerosis: A quantitative description.

In multiple sclerosis (MS), eye movement disorders are common and can be quantified with infrared video-oculography. A well-known abnormality is internuclear ophthalmoplegia (INO). This study aims to describe saccadic abnormalities beyond INO and investigate their clinical relevance. A validated standardized infrared oculography protocol, DEMoNS, was used for quantifying saccadic eye movements in three different tasks in MS patients and healthy controls. The relationship between the saccadic parameters and disease characteristics was investigated. Furthermore, the association between saccadic parameters and visual functioning was analysed using logistic regression models, adjusted for possible confounders. This cross-sectional study included 218 subjects with MS and 58 healthy controls. The latency of all saccades was longer in MS patients than in healthy controls. This saccadic delay was larger in subjects with a longer disease duration and more disabled subjects. Furthermore, it was significantly related to presence of a lower vision-related quality of life. This study provided a comprehensive overview of performance of MS patients in different saccadic tasks, compared to healthy controls. Saccadic delay in MS patients was present in all saccadic tasks and was related to advancing disease and visual functioning in daily life.

Saccadic fatigability in the oculomotor system.

BACKGROUND: Fatigue is one of the most common and disabling symptoms in multiple sclerosis (MS), but challenging to quantify. This prospective study investigated if repeated saccadic eye movements enable measurement of oculomotor fatigability and can reflect on perceived fatigue in MS. METHODS: A standardized infrared oculography protocol (DEMoNS) was used for quantifying saccades in MS patients and healthy controls which included a first and a repeated pro-saccadic task (FPT and RPT). Saccadic peak velocity, latency, gain, area under the curve (AUC) and peak velocity divided by amplitude (Pv/Am) were calculated in both tasks. Perception based fatigue was assessed using the Checklist Individual Strength and the Neurological Fatigue Index (NFI). Linear regression models were used for assessing the relation between saccadic parameters and perceived fatigue. RESULTS: This study included 181 MS patients and 58 healthy controls subjects. From FPT to RPT, there were significant changes in saccadic parameters. Latency of both tasks was significantly related to NFI summary score (FPT: ß = 0.022, p = .049, RPT: ß 0.023, p = .021). These relationships were weakened after adjustment for Expanded Disability Status score (p > .05). There was however no significant group difference in changes in saccadic parameters. CONCLUSIONS: This study presents an objective and reproducible method for measuring saccadic fatigability. Saccadic fatigability was found to be of limited use in MS, and should be tested in conditions affecting ocular muscles or the neuromuscular junction.

Diagnosing and quantifying a common deficit in multiple sclerosis: Internuclear ophthalmoplegia.

OBJECTIVE: We present an objective and quantitative approach for diagnosing internuclear ophthalmoplegia (INO) in multiple sclerosis (MS). METHODS: A validated standardized infrared oculography protocol (DEMoNS [Demonstrate Eye Movement Networks with Saccades]) was used for quantifying prosaccades in patients with MS and healthy controls (HCs). The versional dysconjugacy index (VDI) was calculated, which describes the ratio between the abducting and adducting eye. The VDI was determined for peak velocity, peak acceleration, peak velocity divided by amplitude, and area under the curve (AUC) of the saccadic trajectory. We calculated the diagnostic accuracy for the several VDI parameters by a receiver operating characteristic analysis comparing HCs and patients with MS. The National Eye Institute Visual Function Questionnaire-25 was used to investigate vision-related quality of life of MS patients with INO. RESULTS: Two hundred ten patients with MS and 58 HCs were included. The highest diagnostic accuracy was achieved by the VDI AUC of 15° horizontal prosaccades. Based on a combined VDI AUC and peak velocity divided by amplitude detection, the prevalence of an INO in MS calculated to 34%. In the INO group, 35.2% of the patients with MS reported any complaints of double vision, compared to 18.4% in the non-INO group (p = 0.010). MS patients with an INO had a lower overall vision-related quality of life (median 89.9, interquartile range 12.8) compared to patients without an INO (median 91.8, interquartile range 9.3, p = 0.011). CONCLUSIONS: This study provides an accurate quantitative and clinically relevant definition of an INO in MS. This infrared oculography-based INO standard will require prospective validation. The high prevalence of INO in MS provides an anatomically well described and accurately quantifiable model for treatment trials in MS.

A standardized protocol for quantification of saccadic eye movements: DEMoNS.

OBJECTIVE: Quantitative saccadic testing is a non-invasive method of evaluating the neural networks involved in the control of eye movements. The aim of this study is to provide a standardized and reproducible protocol for infrared oculography measurements of eye movements and analysis, which can be applied for various diseases in a multicenter setting. METHODS: Development of a protocol to Demonstrate Eye Movement Networks with Saccades (DEMoNS) using infrared oculography. Automated analysis methods were used to calculate parameters describing the characteristics of the saccadic eye movements. The two measurements of the subjects were compared with descriptive and reproducibility statistics. RESULTS: Infrared oculography measurements of all subjects were performed using the DEMoNS protocol and various saccadic parameters were calculated automatically from 28 subjects. Saccadic parameters such as: peak velocity, latency and saccade pair ratios showed excellent reproducibility (intra-class correlation coefficients > 0.9). Parameters describing performance of more complex tasks showed moderate to good reproducibility (intra-class correlation coefficients 0.63-0.78). CONCLUSIONS: This study provides a standardized and transparent protocol for measuring and analyzing saccadic eye movements in a multicenter setting. The DEMoNS protocol details outcome measures for treatment trial which are of excellent reproducibility. The DEMoNS protocol can be applied to the study of saccadic eye movements in various neurodegenerative and motor diseases.