title: Distributed abnormalities of brain white matter architecture in patients with dominant optic atrophy and OPA1 mutations.
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.
authors: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina, 60, 20132, Milan, Italy.
authors: Maria A
authors: MA
authors: Rocca
authors: Stefania
authors: S
authors: Bianchi-Marzoli
authors: Roberta
authors: R
authors: Messina
authors: Maria Lucia
authors: ML
authors: Cascavilla
authors: Massimo
authors: M
authors: Zeviani
authors: Costanza
authors: C
authors: Lamperti
authors: Jacopo
authors: J
authors: Milesi
authors: Arturo
authors: A
authors: Carta
authors: Gabriella
authors: G
authors: Cammarata
authors: Letizia
authors: L
authors: Leocani
authors: Eleonora
authors: E
authors: Lamantea
authors: Francesco
authors: F
authors: Bandello
authors: Giancarlo
authors: G
authors: Comi
authors: Andrea
authors: A
authors: Falini
authors: Massimo
authors: M
authors: Filippi
mesh_terms: D000328:Adult; D016880:Anisotropy; D003941:Diagnostic Techniques, Ophthalmological; D038524:Diffusion Magnetic Resonance Imaging; D004569:Electroencephalography; D005072:Evoked Potentials, Auditory / Q000235:genetics / Q000502:physiology; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009460:Neurologic Examination; D029241:Optic Atrophy, Autosomal Dominant / Q000235:genetics* / Q000473:pathology*; D018709:Statistics, Nonparametric; D066127:White Matter / Q000473:pathology*; D055815:Young Adult
chemical_list: D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human