RT Journal Article
SR Electronic
T1 Diffusion Tensor Imaging Mapping of Brain White Matter Pathology in Mitochondrial Optic Neuropathies
JF American Journal of Neuroradiology
JO Am. J. Neuroradiol.
FD American Society of Neuroradiology
DO 10.3174/ajnr.A4272
A1 D.N. Manners
A1 G. Rizzo
A1 C. La Morgia
A1 C. Tonon
A1 C. Testa
A1 P. Barboni
A1 E. Malucelli
A1 M.L. Valentino
A1 L. Caporali
A1 D. Strobbe
A1 V. Carelli
A1 R. Lodi
YR 2015
UL http://www.ajnr.org/content/early/2015/03/19/ajnr.A4272.abstract
AB BACKGROUND AND PURPOSE: Brain white matter is frequently affected in mitochondrial diseases; optic atrophy gene 1-autosomal dominant optic atrophy and Leber hereditary optic neuropathy are the most frequent mitochondrial monosymptomatic optic neuropathies. In this observational study, brain white matter microstructure was characterized by DTI in patients with optic atrophy gene 1-autosomal dominant optic atrophy and Leber hereditary optic neuropathy, in relation to clinical and genetic features. MATERIALS AND METHODS: Nineteen patients with optic atrophy gene 1-autosomal dominant optic atrophy and 17 with Leber hereditary optic neuropathy older than 18 years of age, all genetically diagnosed, and 19 healthy volunteers underwent DTI by using a 1.5T MR imaging scanner and neurologic and ophthalmologic assessments. Brain white matter DTI metrics were calculated for all participants, and, in patients, their correlations with genetics and clinical findings were calculated. RESULTS: Compared with controls, patients with optic atrophy gene 1-autosomal dominant optic atrophy had an increased mean diffusivity in 29.2% of voxels analyzed within major white matter tracts distributed throughout the brain, while fractional anisotropy was reduced in 30.3% of voxels. For patients with Leber hereditary optic neuropathy, the proportion of altered voxels was only 0.5% and 5.5%, respectively, of which half was found within the optic radiation and 3.5%, in the smaller acoustic radiation. In almost all regions, fractional anisotropy diminished with age in patients with optic atrophy gene 1-autosomal dominant optic atrophy and correlated with average retinal nerve fiber layer thickness in several areas. Mean diffusivity increased in those with a missense mutation. Patients with Leber hereditary optic neuropathy taking idebenone had slightly milder changes. CONCLUSIONS: Patients with Leber hereditary optic neuropathy had preferential involvement of the optic and acoustic radiations, consistent with trans-synaptic degeneration, whereas patients with optic atrophy gene 1-autosomal dominant optic atrophy presented with widespread involvement suggestive of a multisystemic, possibly a congenital/developmental, disorder. White matter changes in Leber hereditary optic neuropathy and optic atrophy gene 1-autosomal dominant optic atrophy may be exploitable as biomarkers. Abbreviations DOAautosomal dominant optic atrophyFAfractional anisotropyLHONLeber hereditary optic neuropathyMDmean diffusivityOPA1optic atrophy gene 1ORoptic radiationRNFLretinal nerve fiber layerTBSStract-based spatial statistics