The multiple sclerosis visual pathway cohort: understanding neurodegeneration in MS

Martínez-Lapiscina, Elena H.; Fraga-Pumar, Elena; Gabilondo, Iñigo; Martínez‐Heras, Eloy; Torres-Torres, Rubén; Ortiz-Pérez, Santiago; Llufriú, Sara; Tercero, Ana; Andorrà, Magí; Roca, Marc Figueras; Lampert, Erika J.; Zubizarreta, Irati; Sáiz, Albert; Sánchez-Dalmau, Bernardo; Villoslada, Pablo

doi:10.1186/1756-0500-7-910

Cited by 27 publications

(23 citation statements)

References 57 publications

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“…Correlations between visual dysfunction and structural measurements in MS have been also reported,[ 9 , 25 , 26 , 32 , 33 ] although few of these studies include CSV and color vision analysis. A reduction in the RNFL is associated with lower LCVA, alterations in color vision, and lower quality of life in MS patients.…”

Section: Discussionmentioning

confidence: 99%

Relationship between Visual Dysfunction and Retinal Changes in Patients with Multiple Sclerosis

Satué¹,

Rodrigo²,

Otı́n³

et al. 2016

PLoS ONE

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AimTo evaluate structural changes in the retina and their correlation with visual dysfunction in patients with multiple sclerosis.MethodsPatients with multiple sclerosis (n = 84) and healthy controls (n = 84) underwent structural evaluation of the retinal nerve fiber layer, and macular and ganglion cell layer thicknesses using Spectral domain optical coherence tomography (SD-OCT). All subjects underwent high and low contrast visual acuity, color vision (using the Farnsworth and L´Anthony desaturated D15 color tests), and contrast sensitivity vision using the Pelli Robson chart and CSV 1000E test.ResultsMacular, retinal nerve fiber layer, and ganglion cell layer thinning was observed in multiple sclerosis patients compared to healthy controls (p<0.05). High- and low-contrast visual acuity and contrast sensitivity vision at four different spatial frequencies were significantly reduced in comparison with healthy subjects (p<0.05). Macular, retinal nerve fiber layer and ganglion cell layer measurements correlated with high and low contrast visual acuity, and contrast sensitivity vision. Contrast sensitivity vision was the functional parameter that most strongly correlated with the structural measurements in multiple sclerosis and was associated with ganglion cell layer measurements. The L´Anthony color vision score (age-corrected color confusion index) was associated with macular measurements.ConclusionsPatients with multiple sclerosis had visual dysfunction that correlated with structural changes evaluated by SD-OCT. Macular and ganglion cell layer measurements may be good indicators of visual impairment in multiple sclerosis patients.

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Section: Discussionmentioning

confidence: 99%

Relationship between Visual Dysfunction and Retinal Changes in Patients with Multiple Sclerosis

Satué¹,

Rodrigo²,

Otı́n³

et al. 2016

PLoS ONE

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“…The Research Ethics Committee of the Hospital Clinic of Barcelona approved the study and all participants provided written informed consent prior to enrollment. The design and methods of the MS-VisualPath cohort have previously been described in detail [9]. We included MS patients according to McDonalds Criteria [Criteria 2005 and 2010] without any psychiatric, neurological, or ocular disorders that may interfere with the aims of the study.…”

Section: Methodsmentioning

confidence: 99%

“…Two or more errors in the NON-eye served to classify the patient as having dyschromatopsia. Further information about how HRR pseudoisochromatic plates can be used to assess color vision in MS has been described in detail [9].…”

Section: Color Vision Assessmentmentioning

confidence: 99%

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Color vision impairment in multiple sclerosis points to retinal ganglion cell damage

et al. 2015

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Multiple Sclerosis (MS) results in color vision impairment regardless of optic neuritis (ON). The exact location of injury remains undefined. The objective of this study is to identify the region leading to dyschromatopsia in MS patients' NON-eyes. We evaluated Spearman correlations between color vision and measures of different regions in the afferent visual pathway in 106 MS patients. Regions with significant correlations were included in logistic regression models to assess their independent role in dyschromatopsia. We evaluated color vision with Hardy-Rand-Rittler plates and retinal damage using Optical Coherence Tomography. We ran SIENAX to measure Normalized Brain Parenchymal Volume (NBPV), FIRST for thalamus volume and Freesurfer for visual cortex areas. We found moderate, significant correlations between color vision and macular retinal nerve fiber layer (rho = 0.289, p = 0.003), ganglion cell complex (GCC = GCIP) (rho = 0.353, p < 0.001), thalamus (rho = 0.361, p < 0.001), and lesion volume within the optic radiations (rho = -0.230, p = 0.030). Only GCC thickness remained significant (p = 0.023) in the logistic regression model. In the final model including lesion load and NBPV as markers of diffuse neuroaxonal damage, GCC remained associated with dyschromatopsia [OR = 0.88 95 % CI (0.80-0.97) p = 0.016]. This association remained significant when we also added sex, age, and disease duration as covariates in the regression model. Dyschromatopsia in NON-eyes is due to damage of retinal ganglion cells (RGC) in MS. Color vision can serve as a marker of RGC damage in MS.

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“…The validation cohort was a prospective cohort of 120 MS patients from the Hospital Clinic of Barcelona, with annual clinical (EDSS) and MRI assessment over three years (raw data for the EDSS and BV time-series are provided in the S2 File ). More details of this cohort can be found elsewhere [ 31 ].…”

Section: Methodsmentioning

confidence: 99%

Dynamics and heterogeneity of brain damage in multiple sclerosis

et al. 2017

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Multiple Sclerosis (MS) is an autoimmune disease driving inflammatory and degenerative processes that damage the central nervous system (CNS). However, it is not well understood how these events interact and evolve to evoke such a highly dynamic and heterogeneous disease. We established a hypothesis whereby the variability in the course of MS is driven by the very same pathogenic mechanisms responsible for the disease, the autoimmune attack on the CNS that leads to chronic inflammation, neuroaxonal degeneration and remyelination. We propose that each of these processes acts more or less severely and at different times in each of the clinical subgroups. To test this hypothesis, we developed a mathematical model that was constrained by experimental data (the expanded disability status scale [EDSS] time series) obtained from a retrospective longitudinal cohort of 66 MS patients with a long-term follow-up (up to 20 years). Moreover, we validated this model in a second prospective cohort of 120 MS patients with a three-year follow-up, for which EDSS data and brain volume time series were available. The clinical heterogeneity in the datasets was reduced by grouping the EDSS time series using an unsupervised clustering analysis. We found that by adjusting certain parameters, albeit within their biological range, the mathematical model reproduced the different disease courses, supporting the dynamic CNS damage hypothesis to explain MS heterogeneity. Our analysis suggests that the irreversible axon degeneration produced in the early stages of progressive MS is mainly due to the higher rate of myelinated axon degeneration, coupled to the lower capacity for remyelination. However, and in agreement with recent pathological studies, degeneration of chronically demyelinated axons is not a key feature that distinguishes this phenotype. Moreover, the model reveals that lower rates of axon degeneration and more rapid remyelination make relapsing MS more resilient than the progressive subtype. Therefore, our results support the hypothesis of a common pathogenesis for the different MS subtypes, even in the presence of genetic and environmental heterogeneity. Hence, MS can be considered as a single disease in which specific dynamics can provoke a variety of clinical outcomes in different patient groups. These results have important implications for the design of therapeutic interventions for MS at different stages of the disease.

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The multiple sclerosis visual pathway cohort: understanding neurodegeneration in MS

Cited by 27 publications

References 57 publications

Relationship between Visual Dysfunction and Retinal Changes in Patients with Multiple Sclerosis

Relationship between Visual Dysfunction and Retinal Changes in Patients with Multiple Sclerosis

Color vision impairment in multiple sclerosis points to retinal ganglion cell damage

Dynamics and heterogeneity of brain damage in multiple sclerosis

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