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Dissecting structure-function interactions in acute optic neuritis to investigate neuroplasticity.

ABSTRACT: Structural MRI, electrophysiology, and functional MRI (fMRI) elucidate different aspects of damage and repair in demyelinating diseases. We combined them to investigate why patients with optic neuritis (ON) exhibit a wide variation in severity of acute visual loss, with the following objectives: (1) To determine how structural and electrophysiological changes in the anterior and posterior visual pathways contribute to acute visual loss. (2) To combine these data with fMRI, to investigate whether cortical activity modulates visual acuity. The visual system of 28 patients with acute unilateral ON was assessed. Linear regression modeling was used to identify parameters associated with acute visual loss, and to determine whether fMRI activity was associated with vision, after accounting for structural and electrophysiological predictors, age, and gender. Optic nerve lesion length and visual evoked potential (VEP) amplitude were associated with visual loss. Bilateral activation in the extra-striate occipital cortex correlated directly with vision, after adjusting for optic nerve lesion length, VEP amplitude, and demographic characteristics. These data suggest that acute visual loss is associated with the extent of inflammation and conduction block in the optic nerve, but not with pathology in the optic radiations or occipital cortex. The association of better vision with greater fMRI responses, after accounting for factors which reduce afferent input, suggests a role for adaptive neuroplasticity within the association cortex of the dorsal stream of higher visual processing. Longitudinal studies will clarify whether different extra-striate cortical regions play a role in adaptive plasticity in the acute and chronic stages of injury.

SUBMITTER: Jenkins T

PROVIDER: S-EPMC6870769 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

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Dissecting structure-function interactions in acute optic neuritis to investigate neuroplasticity.

Jenkins Thomas T Ciccarelli Olga O Toosy Ahmed A Miszkiel Katherine K Wheeler-Kingshott Claudia C Altmann Daniel D Mancini Laura L Jones Steve S Plant Gordon G Miller David D Thompson Alan A

Human brain mapping 20100201 2

Structural MRI, electrophysiology, and functional MRI (fMRI) elucidate different aspects of damage and repair in demyelinating diseases. We combined them to investigate why patients with optic neuritis (ON) exhibit a wide variation in severity of acute visual loss, with the following objectives: (1) To determine how structural and electrophysiological changes in the anterior and posterior visual pathways contribute to acute visual loss. (2) To combine these data with fMRI, to investigate whether ...[more]

PMID: 19662659

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Project description:IMPORTANCE Retrospective studies have demonstrated disparate outcomes following acute optic neuritis in individuals of African descent compared with individuals of white race/ethnicity. However, published analyses of the prospectively collected Optic Neuritis Treatment Trial (ONTT) data identified no association between worse visual outcomes and black race/ethnicity. OBJECTIVES To investigate the associations of age, sex, and race/ethnicity with visual outcomes following acute optic neuritis through application of longitudinal data analysis techniques to the ONTT data set. DESIGN Secondary analysis of the ONTT (a prospective randomized controlled trial) data set. Our models included effects of treatment (placebo, oral prednisone, or intravenous methylprednisolone), time, and treatment × time interaction, as well as demographic covariates of age, sex, and race/ethnicity. SETTING AND PARTICIPANTS The ONTT data were collected at multiple centers in the United States. Patients of black (n = 58) and white (n = 388) race/ethnicity with acute optic neuritis who enrolled in the ONTT within 8 days of symptom onset were included in analyses. MAIN OUTCOMES AND MEASURES The contrast sensitivity and visual acuity (logMAR) in the affected eye were modeled using 2-stage mixed-effects regression techniques. All available follow-up data from baseline to 15 to 18 years were included. RESULTS The data identified no relationship of age, sex, or treatment with contrast sensitivity or visual acuity outcomes. Race/ethnicity was significantly related to contrast sensitivity (P < .001) and visual acuity (P < .001) during a 15-year period following acute optic neuritis, with black race/ethnicity being associated with worse scores for both. CONCLUSIONS AND RELEVANCE Race/ethnicity seems to be associated with contrast sensitivity and visual acuity outcomes in affected eyes following acute optic neuritis. To our knowledge, this is the largest cohort of black race/ethnicity with acute optic neuritis to be studied and represents the first evidence from a prospectively collected data set to support a hypothesis of race/ethnicity-dependent visual outcomes of acute optic neuritis.

Project description:Optic neuritis (ON) often occurs at the presentation of multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD). The recommended treatment of high-dose corticosteroids for ON is based on a North American study population, which did not address treatment timing or antibody serostatus. The Acute Optic Neuritis Network (ACON) presents a global, prospective, observational study protocol primarily designed to investigate the effect of time to high-dose corticosteroid treatment on 6-month visual outcomes in ON. Patients presenting within 30 days of the inaugural ON will be enrolled. For the primary analysis, patients will subsequently be assigned into the MS-ON group, the aquapotin-4-IgG positive ON (AQP4-IgG+ON) group or the MOG-IgG positive ON (MOG-IgG+ON) group and then further sub-stratified according to the number of days from the onset of visual loss to high-dose corticosteroids (days-to-Rx). The primary outcome measure will be high-contrast best-corrected visual acuity (HC-BCVA) at 6 months. In addition, multimodal data will be collected in subjects with any ON (CIS-ON, MS-ON, AQP4-IgG+ON or MOG-IgG+ON, and seronegative non-MS-ON), excluding infectious and granulomatous ON. Secondary outcomes include low-contrast best-corrected visual acuity (LC-BCVA), optical coherence tomography (OCT), magnetic resonance imaging (MRI) measurements, serum and cerebrospinal fluid (CSF) biomarkers (AQP4-IgG and MOG-IgG levels, neurofilament, and glial fibrillary protein), and patient reported outcome measures (headache, visual function in daily routine, depression, and quality of life questionnaires) at presentation at 6-month and 12-month follow-up visits. Data will be collected from 28 academic hospitals from Africa, Asia, the Middle East, Europe, North America, South America, and Australia. Planned recruitment consists of 100 MS-ON, 50 AQP4-IgG+ON, and 50 MOG-IgG+ON. This prospective, multimodal data collection will assess the potential value of early high-dose corticosteroid treatment, investigate the interrelations between functional impairments and structural changes, and evaluate the diagnostic yield of laboratory biomarkers. This analysis has the ability to substantially improve treatment strategies and the accuracy of diagnostic stratification in acute demyelinating ON.Trial registrationClinicalTrials.gov, identifier: NCT05605951.

Dataset Information

Dissecting structure-function interactions in acute optic neuritis to investigate neuroplasticity.

Publications

Dissecting structure-function interactions in acute optic neuritis to investigate neuroplasticity.

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