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Relationships between retinal axonal and neuronal measures and global central nervous system pathology in multiple sclerosis.

ABSTRACT: 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.

SUBMITTER: Saidha S

PROVIDER: S-EPMC4030557 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Relationships between retinal axonal and neuronal measures and global central nervous system pathology in multiple sclerosis.

Saidha Shiv S Sotirchos Elias S ES Oh Jiwon J Syc Stephanie B SB Seigo Michaela A MA Shiee Navid N Eckstein Chistopher C Durbin Mary K MK Oakley Jonathan D JD Meyer Scott A SA Frohman Teresa C TC Newsome Scott S Ratchford John N JN Balcer Laura J LJ Pham Dzung L DL Crainiceanu Ciprian M CM Frohman Elliot M EM Reich Daniel S DS Calabresi Peter A PA

JAMA neurology 20130101 1

<h4>Objective</h4>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).<h4>Design</h4>Cross-sectional study.<h4>Setting</h4>Johns Hopkins University, Baltimore, Maryland.<h4>Participants</h4>A total of 84 patients with MS and 24 healthy control subjects.<h4>Main outcome measures</h4>High-definitio ...[more]

PMID: 23318513

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Project description:IntroductionRecent studies have implicated changes in the blood-central nervous system barriers (BCNSB) in amyotrophic lateral sclerosis (ALS). The objective of this scoping review is to synthesize the current evidence for BCNSB structure and functional abnormalities in ALS studies and propose how BCNSB pathology may impact therapeutic development.MethodsA literature search was conducted using Ovid Medline, EMBASE, and Web of Science, from inception to November 2021 and limited to entries in English language. Simplified search strategy included the terms ALS/motor neuron disease and [BCNSB or blood-brain barrier (BBB) or blood-spinal cord barrier (BSCB)]. Henceforth, BCNSB is used as a term that is inclusive of the BBB and BSCB. Four independent reviewers conducted a title and abstract screening, hand-searched the reference lists of review papers, and performed a full text review of eligible studies. Included studies were original peer-reviewed full text publications, evaluating the structure and function of the BCNSB in preclinical models of ALS, clinical ALS, or postmortem human ALS tissue. There was no restriction on study design. The four reviewers independently extracted the data.ResultsThe search retrieved 2,221 non-duplicated articles and 48 original studies were included in the synthesis. There was evidence that the integrity of the BCNSB is disrupted throughout the course of the disease in rodent models, beginning prior to symptom onset and detectable neurodegeneration. Increased permeability, pharmacoresistance with upregulated efflux transporters, and morphological changes in the supporting cells of the BCNSB, including pericytes, astrocytes, and endothelial cells were observed in animal models. BCNSB abnormalities were also demonstrated in postmortem studies of ALS patients. Therapeutic interventions targeting BCNSB dysfunction were associated with improved motor neuron survival in animal models of ALS.ConclusionBCNSB structural and functional abnormalities are likely implicated in ALS pathophysiology and may occur upstream to neurodegeneration. Promising therapeutic strategies targeting BCNSB dysfunction have been tested in animals and can be translated into ALS clinical trials.

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Dataset Information

Relationships between retinal axonal and neuronal measures and global central nervous system pathology in multiple sclerosis.

Publications

Relationships between retinal axonal and neuronal measures and global central nervous system pathology in multiple sclerosis.

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