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

TitleDistributed abnormalities of brain white matter architecture in patients with dominant optic atrophy and OPA1 mutations.
Publication TypeJournal Article
Year of Publication2015
AuthorsRocca, MA, Bianchi-Marzoli, S, Messina, R, Cascavilla, MLucia, Zeviani, M, Lamperti, C, Milesi, J, Carta, A, Cammarata, G, Leocani, L, Lamantea, E, Bandello, F, Comi, G, Falini, A, Filippi, M
JournalJ Neurol
Date Published2015 May
KeywordsAdult, Anisotropy, Diagnostic Techniques, Ophthalmological, Diffusion Magnetic Resonance Imaging, Electroencephalography, Evoked Potentials, Auditory, Female, GTP Phosphohydrolases, Humans, Male, Middle Aged, Mutation, Neurologic Examination, Optic Atrophy, Autosomal Dominant, Statistics, Nonparametric, White Matter, Young Adult

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.

Alternate JournalJ. Neurol.
Citation Key10.1007/s00415-015-7696-5
PubMed ID25794858
Grant ListMC_UP_1002/1 / / Medical Research Council / United Kingdom