Improvement of internuclear ophthalmoparesis in multiple sclerosis with dalfampridine

Serra, Alessandro; Skelly, Margaret; Jacobs, Joseph B.; Walker, Mark F.; Cohen, Jeffrey A.

doi:10.1212/wnl.0000000000000567

Cited by 13 publications

(5 citation statements)

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“…Such approach of studying the MLF as a composite structural-functional biomarker of axonal and myelin status could be used to assess response to therapies aimed at enhancing recovery and fidelity of axonal transmission in MS. In this regard, preliminary data in three INO patients treated with the potassium channel blocker dalfampridine showed changes in horizontal saccadic conjugacy, consistent with improved transmission of the neural pulse responsible for adducting movements ( 49 ).…”

Section: Eye Movements As Model and Marker Of Disease In Msmentioning

confidence: 82%

Eye Movement Abnormalities in Multiple Sclerosis: Pathogenesis, Modeling, and Treatment

2018

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Multiple sclerosis (MS) commonly causes eye movement abnormalities that may have a significant impact on patients’ disability. Inflammatory demyelinating lesions, especially occurring in the posterior fossa, result in a wide range of disorders, spanning from acquired pendular nystagmus (APN) to internuclear ophthalmoplegia (INO), among the most common. As the control of eye movements is well understood in terms of anatomical substrate and underlying physiological network, studying ocular motor abnormalities in MS provides a unique opportunity to gain insights into mechanisms of disease. Quantitative measurement and modeling of eye movement disorders, such as INO, may lead to a better understanding of common symptoms encountered in MS, such as Uhthoff’s phenomenon and fatigue. In turn, the pathophysiology of a range of eye movement abnormalities, such as APN, has been clarified based on correlation of experimental model with lesion localization by neuroimaging in MS. Eye movement disorders have the potential of being utilized as structural and functional biomarkers of early cognitive deficit, and possibly help in assessing disease status and progression, and to serve as platform and functional outcome to test novel therapeutic agents for MS. Knowledge of neuropharmacology applied to eye movement dysfunction has guided testing and use of a number of pharmacological agents to treat some eye movement disorders found in MS, such as APN and other forms of central nystagmus.

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Section: Eye Movements As Model and Marker Of Disease In Msmentioning

confidence: 82%

Eye Movement Abnormalities in Multiple Sclerosis: Pathogenesis, Modeling, and Treatment

2018

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“…A case study in 2014 and a recent placebo-controlled study showed that fampridine decreases the adduction delay in patients with MS and INO, measured with high-frequency infrared oculography. 29,30…”

Section: Discussionmentioning

confidence: 99%

Diagnosing and quantifying a common deficit in multiple sclerosis

et al. 2019

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ObjectiveWe present an objective and quantitative approach for diagnosing internuclear ophthalmoplegia (INO) in multiple sclerosis (MS).MethodsA 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.ResultsTwo 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).ConclusionsThis 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.

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“…Abnormal eye movements can be detected readily at the bedside but are not captured well by the standard multiple sclerosis disability rating scales such as the Expanded Disability Status Scale (EDSS); more detailed quantitative characterization requires sophisticated eye movement recording and analysis. Fatigue of adducting saccades in internuclear ophthalmoparesis in multiple sclerosis and improvement with dalfampridine have been demonstrated using such technology ( Serra et al , 2014 ). Interestingly, abnormalities of saccades appeared to be associated with generalized fatigue in patients with multiple sclerosis ( Finke et al , 2012 ).…”

Section: Afferent Visual Manifestations In Optic Neuritis and Multiplmentioning

confidence: 99%

Vision and vision-related outcome measures in multiple sclerosis

Balcer

Miller

Reingold³

et al. 2014

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Visual impairment is a key manifestation of multiple sclerosis. Acute optic neuritis is a common, often presenting manifestation, but visual deficits and structural loss of retinal axonal and neuronal integrity can occur even without a history of optic neuritis. Interest in vision in multiple sclerosis is growing, partially in response to the development of sensitive visual function tests, structural markers such as optical coherence tomography and magnetic resonance imaging, and quality of life measures that give clinical meaning to the structure-function correlations that are unique to the afferent visual pathway. Abnormal eye movements also are common in multiple sclerosis, but quantitative assessment methods that can be applied in practice and clinical trials are not readily available. We summarize here a comprehensive literature search and the discussion at a recent international meeting of investigators involved in the development and study of visual outcomes in multiple sclerosis, which had, as its overriding goals, to review the state of the field and identify areas for future research. We review data and principles to help us understand the importance of vision as a model for outcomes assessment in clinical practice and therapeutic trials in multiple sclerosis.

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Improvement of internuclear ophthalmoparesis in multiple sclerosis with dalfampridine

Cited by 13 publications

References 4 publications

Eye Movement Abnormalities in Multiple Sclerosis: Pathogenesis, Modeling, and Treatment

Eye Movement Abnormalities in Multiple Sclerosis: Pathogenesis, Modeling, and Treatment

Diagnosing and quantifying a common deficit in multiple sclerosis

Vision and vision-related outcome measures in multiple sclerosis

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