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      Retinal measures correlate with cognitive and physical disability in early multiple sclerosis

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          Is Open Access

          Recommendations for a Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS)

          Background: Cognitive impairment in MS impacts negatively on many patients at all disease stages and in all subtypes. Full clinical cognitive assessment is expensive, requiring expert staff and special equipment. Test versions and normative data are not available for all languages and cultures. Objective: To recommend a brief cognitive assessment for multiple sclerosis (MS) that is optimized for small centers, with one or few staff members, who may not have neuropsychological training and constructed to maximize international use. Methods: An expert committee of twelve members representing the main cultural groups that have so far contributed considerable data about MS cognitive dysfunction was convened. Following exhaustive literature review, peer-reviewed articles were selected to cover a broad spectrum of cultures and scales that targeted cognitive domains vulnerable to MS. Each was rated by two committee members and candidates scales were rated on psychometric qualities (reliability, validity, and sensitivity), international application, ease of administration, feasibility in the specified context, and acceptability to patients. Results: The committee recommended the Symbol Digit Modalities Test, if only 5 minutes was available, with the addition of the California Verbal Learning Test – Second Edition and the Brief Visuospatial Memory Test – Revised learning trials if a further 10 minutes could be allocated for testing. Conclusions: A brief cognitive assessment for MS has been recommended. A validation protocol has been prepared for language groups and validation studies have commenced.
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            Relationships between retinal axonal and neuronal measures and global central nervous system pathology in multiple sclerosis.

            To determine the relationships between conventional and segmentation-derived optical coherence tomography (OCT) retinal layer thickness measures with intracranial volume (a surrogate of head size) and brain substructure volumes in multiple sclerosis (MS). Cross-sectional study. Johns Hopkins University, Baltimore, Maryland. A total of 84 patients with MS and 24 healthy control subjects. High-definition spectral-domain OCT conventional and automated segmentation-derived discrete retinal layer thicknesses and 3-T magnetic resonance imaging brain substructure volumes. Peripapillary retinal nerve fiber layer as well as composite ganglion cell layer+inner plexiform layer thicknesses in the eyes of patients with MS without a history of optic neuritis were associated with cortical gray matter (P=.01 and P=.04, respectively) and caudate (P=.04 and P=.03, respectively) volumes. Inner nuclear layer thickness, also in eyes without a history of optic neuritis, was associated with fluid-attenuated inversion recovery lesion volume (P=.007) and inversely associated with normal-appearing white matter volume (P=.005) in relapsing-remitting MS. As intracranial volume was found to be related with several of the OCT measures in patients with MS and healthy control subjects and is already known to be associated with brain substructure volumes, all OCT-brain substructure relationships were adjusted for intracranial volume. CONCLUSIONS Retinal measures reflect global central nervous system pathology in multiple sclerosis, with thicknesses of discrete retinal layers each appearing to be associated with distinct central nervous system processes. Moreover, OCT measures appear to correlate with intracranial volume in patients with MS and healthy control subjects, an important unexpected factor unaccounted for in prior studies examining the relationships between peripapillary retinal nerve fiber layer thickness and brain substructure volumes.
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              Diagnostic accuracy of retinal abnormalities in predicting disease activity in MS.

              To assess the association between the thickness of the retinal nerve fiber layer (RNFL), assessed by optical coherence tomography (OCT), retinal periphlebitis (RP), and multiple sclerosis (MS) disease activity. We studied a prospective cohort of 61 patients and 29 matched controls for 2 years, performing a neurologic assessment every 3 months and an ophthalmologic evaluation, including OCT scans, every 6 months. Baseline MRI studies were also carried out from which brain volume and lesion load were assessed. We found that the RNFL thickness in patients with MS was thinner than in controls, particularly in the temporal quadrant (p = 0.004). Although RNFL atrophy was greater in patients who also had optic neuritis (p = 0.002), it also augmented in MS patients who did not have optic neuritis compared with controls (p = 0.014). RNFL atrophy was correlated with greater disability (r = -0.348, p = 0.001) and longer disease duration (r = -0.301, p = 0.003). Furthermore, baseline temporal quadrant RNFL atrophy was associated with the presence of new relapses and changes in the Expanded Disability Status Scale by the end of the study (p < 0.05 in all cases). Indeed, RNFL thickness was correlated with white matter volume (r = 0.291, p = 0.005) and gray matter volume (r = 0.239, p = 0.021). The presence of RP was a risk factor for having new relapses in the next 2 years (odds ratio = 1.52, p = 0.02), and patients with RP had larger gadolinium-enhancing lesions volume (p = 0.003). Retinal nerve fiber layer atrophy and the presence of retinal periphlebitis are associated with disease activity, suggesting that retinal evaluation can be used as biomarkers of multiple sclerosis activity.
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                Author and article information

                Journal
                Journal of Neurology
                J Neurol
                Springer Science and Business Media LLC
                0340-5354
                1432-1459
                November 2016
                August 20 2016
                November 2016
                : 263
                : 11
                : 2287-2295
                Article
                10.1007/s00415-016-8271-4
                27544501
                1a63ad3c-3c5e-4e1d-8a16-d2c0473b197c
                © 2016

                http://www.springer.com/tdm

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