Dataset Information

A composite measure to explore visual disability in primary progressive multiple sclerosis.

ABSTRACT:

Background

Optical coherence tomography (OCT) and magnetic resonance imaging (MRI) can provide complementary information on visual system damage in multiple sclerosis (MS).

Objectives

The objective of this paper is to determine whether a composite OCT/MRI score, reflecting cumulative damage along the entire visual pathway, can predict visual deficits in primary progressive multiple sclerosis (PPMS).

Methods

Twenty-five PPMS patients and 20 age-matched controls underwent neuro-ophthalmologic evaluation, spectral-domain OCT, and 3T brain MRI. Differences between groups were assessed by univariate general linear model and principal component analysis (PCA) grouped instrumental variables into main components. Linear regression analysis was used to assess the relationship between low-contrast visual acuity (LCVA), OCT/MRI-derived metrics and PCA-derived composite scores.

Results

PCA identified four main components explaining 80.69% of data variance. Considering each variable independently, LCVA 1.25% was significantly predicted by ganglion cell-inner plexiform layer (GCIPL) thickness, thalamic volume and optic radiation (OR) lesion volume (adjusted R² 0.328, p?=?0.00004; adjusted R² 0.187, p?=?0.002 and adjusted R² 0.180, p?=?0.002). The PCA composite score of global visual pathway damage independently predicted both LCVA 1.25% (adjusted R² value 0.361, p?=?0.00001) and LCVA 2.50% (adjusted R² value 0.323, p?=?0.00003).

Conclusion

A multiparametric score represents a more comprehensive and effective tool to explain visual disability than a single instrumental metric in PPMS.

SUBMITTER: Poretto V

PROVIDER: S-EPMC5439656 | biostudies-literature | 2017 Apr-Jun

REPOSITORIES: biostudies-literature

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Publications

A composite measure to explore visual disability in primary progressive multiple sclerosis.

Poretto Valentina V Petracca Maria M Saiote Catarina C Mormina Enricomaria E Howard Jonathan J Miller Aaron A Lublin Fred D FD Inglese Matilde M

Multiple sclerosis journal - experimental, translational and clinical 20170401 2

<h4>Background</h4>Optical coherence tomography (OCT) and magnetic resonance imaging (MRI) can provide complementary information on visual system damage in multiple sclerosis (MS).<h4>Objectives</h4>The objective of this paper is to determine whether a composite OCT/MRI score, reflecting cumulative damage along the entire visual pathway, can predict visual deficits in primary progressive multiple sclerosis (PPMS).<h4>Methods</h4>Twenty-five PPMS patients and 20 age-matched controls underwent neu ...[more]

PMID: 28607759

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Project description:Grey matter atrophy has been shown in primary progressive multiple sclerosis (PPMS), but its association with physical incapacity is unclear. We submitted 19 patients with PPMS to a neurological evaluation and brain magnetic resonance imaging (MRI) with volumetric analysis using FreeSurfer. We found no relation between the Expanded Disability Status Scale or disease duration and the grey matter or white matter structures analysed. Lesion load was negatively correlated with cortical and subcortical grey matter volumes, but not with total white matter volume. We concluded that physical disability in PPMS is not directly related to brain atrophy and that focal inflammatory white matter lesions may contribute to progressive neuronal degeneration.Primary progressive multiple sclerosis (PPMS) is characterized by chronic progression since onset, with predominant involvement of the spinal cord and prominent neurodegeneration. Grey matter atrophy has been shown in patients with PPMS, but its association with clinical incapacity is uncertain. We investigated the relationship between regional brain atrophy and physical disability in patients with PPMS.Patients with an established diagnosis of PPMS underwent a neurological evaluation followed by brain MRI at 1.5 T. Volumetric analysis was performed with FreeSurfer software, and evaluated the neocortex, total white matter, total subcortical grey matter, putamen, caudate, globus pallidus, thalamus, hippocampus, brainstem, corpus callosum and pre-central gyrus volumes. Clinical data obtained included physical disability as measured by the Expanded Disability Status Scale (EDSS).Nineteen patients were included, 14 female (73.7%), mean age of 55.7 (SD 7.6) and mean disease duration of 13.0 years (SD 8.8). Median EDSS score was 6.0 (3.5-8.0). The average T1 lesion load (4.9 cm³, SD 3.4) and T2 load (10.5 cm³, SD 9.9) did not relate to disease duration. There was no significant correlation between EDSS score or disease duration and the cortical grey matter, deep grey matter or white matter structures analysed. Lesion load was negatively correlated with cortical and subcortical grey matter volumes (p < 0.05), but not with total white matter volume.Physical disability in PPMS is not directly related to brain volume loss. Grey matter atrophy correlates with lesion load in patients with PPMS, indicating that focal inflammatory white matter lesions may contribute to progressive neuronal degeneration.

Project description:The pathogenic mechanisms contributing to neurological disability in progressive multiple sclerosis (PMS) are poorly understood. Cortical neuronal loss independent of cerebral white matter (WM) demyelination in myelocortical MS (MCMS) and identification of MS patients with widespread cortical atrophy and disability progression independent of relapse activity (PIRA) support pathogenic mechanisms other than cerebral WM demyelination. The three-dimensional distribution and underlying pathology of myelinated T2 lesions were investigated in postmortem MCMS brains. Postmortem brain slices from previously characterized MCMS (10 cases) and typical MS (TMS) cases (12 cases) were co-registered with in situ postmortem T2 hyperintensities and T1 hypointensities. T1 intensity thresholds were used to establish a classifier that differentiates MCMS from TMS. The classifier was validated in 36 uncharacterized postmortem brains and applied to baseline MRIs from 255 living PMS participants enrolled in SPRINT-MS. Myelinated T2 hyperintensities in postmortem MCMS brains have a contiguous periventricular distribution that expands at the occipital poles of the lateral ventricles where a surface-in gradient of myelinated axonal degeneration was observed. The MRI classifier distinguished pathologically confirmed postmortem MCMS and TMS cases with an accuracy of 94%. For SPRINT-MS patients, the MRI classifier identified 78% as TMS, 10% as MCMS, and 12% with a paucity of cerebral T1 and T2 intensities. In SPRINT-MS, expanded disability status scale and brain atrophy measures were similar in MCMS and TMS cohorts. A paucity of cerebral WM demyelination in 22% of living PMS patients raises questions regarding a primary role for cerebral WM demyelination in disability progression in all MS patients and has implications for clinical management of MS patients and clinical trial outcomes in PMS. Periventricular myelinated fiber degeneration provides additional support for surface-in gradients of neurodegeneration in MS.

Dataset Information

A composite measure to explore visual disability in primary progressive multiple sclerosis.

Background

Objectives

Methods

Results

Conclusion

Publications

A composite measure to explore visual disability in primary progressive multiple sclerosis.

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