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01-05-2015 | Original Communication

Distributed abnormalities of brain white matter architecture in patients with dominant optic atrophy and OPA1 mutations

Authors: Maria A. Rocca, Stefania Bianchi-Marzoli, Roberta Messina, Maria Lucia Cascavilla, Massimo Zeviani, Costanza Lamperti, Jacopo Milesi, Arturo Carta, Gabriella Cammarata, Letizia Leocani, Eleonora Lamantea, Francesco Bandello, Giancarlo Comi, Andrea Falini, Massimo Filippi

Published in: Journal of Neurology | Issue 5/2015

Abstract

Using advanced MRI techniques, we investigated the presence and topographical distribution of brain grey matter (GM) and white matter (WM) alterations in dominant optic atrophy (DOA) patients with genetically proven OPA1 mutation as well as their correlation with clinical and neuro-ophthalmologic findings. Nineteen DOA patients underwent neurological, neuro-ophthalmologic and brainstem auditory evoked potentials (BAEP) evaluations. Voxel-wise methods were applied to assess regional GM and WM abnormalities in patients compared to 20 healthy controls. Visual acuity was reduced in 16 patients. Six DOA patients (4 with missense mutations) had an abnormal I peripheral component (auditory nerve) at BAEP. Compared to controls, DOA patients had significant atrophy of the optic nerves (p < 0.0001). Voxel-based morphometry (VBM) analysis showed that, compared to controls, DOA patients had significant WM atrophy of the chiasm and optic tracts; whereas no areas of GM atrophy were found. Tract-based spatial statistics (TBSS) analysis showed that compared to controls, DOA patients had significantly lower mean diffusivity, axial and radial diffusivity in the WM of the cerebellum, brainstem, thalamus, fronto-occipital-temporal lobes, including the cingulum, corpus callosum, corticospinal tract and optic radiation bilaterally. No abnormalities of fractional anisotropy were detected. No correlations were found between volumetric and diffusivity abnormalities quantified with MRI and clinical and neuro-ophthalmologic measures of disease severity. Consistently with pathological studies, tissue loss in DOA patients is limited to anterior optic pathways reflecting retinal ganglion cell degeneration. Distributed abnormalities of diffusivity indexes might reflect abnormal intracellular mitochondrial morphology as well as alteration of protein levels due to OPA1 mutations.

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Title: Distributed abnormalities of brain white matter architecture in patients with dominant optic atrophy and OPA1 mutations
Authors: Maria A. Rocca
Stefania Bianchi-Marzoli
Roberta Messina
Maria Lucia Cascavilla
Massimo Zeviani
Costanza Lamperti
Jacopo Milesi
Arturo Carta
Gabriella Cammarata
Letizia Leocani
Eleonora Lamantea
Francesco Bandello
Giancarlo Comi
Andrea Falini
Massimo Filippi
Publication date: 01-05-2015
Publisher: Springer Berlin Heidelberg
Published in: Journal of Neurology / Issue 5/2015
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-015-7696-5

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Distributed abnormalities of brain white matter architecture in patients with dominant optic atrophy and OPA1 mutations

Abstract

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