title: Diffusion Tensor Imaging Mapping of Brain White Matter Pathology in Mitochondrial Optic Neuropathies.
abstract: OBJECTIVE
  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.
  
  
  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.
authors: From the Functional MR Unit (D.N.M., G.R., C.Tonon, C.Testa, R.L.).
authors: D N
authors: DN
authors: Manners
authors: From the Functional MR Unit (D.N.M., G.R., C.Tonon, C.Testa, R.L.) Neurology Unit (G.R., C.L.M., M.L.V., L.C., D.S., V.C.), Department of Biomedical and NeuroMotor Sciences.
authors: G
authors: G
authors: Rizzo
authors: Neurology Unit (G.R., C.L.M., M.L.V., L.C., D.S., V.C.), Department of Biomedical and NeuroMotor Sciences "Istituto di Ricovero e Cura a Carattere Scientifico Istituto delle Scienze Neurologiche di Bologna" (C.L.M., M.L.V., L.C., D.S., V.C.), Bologna, Italy.
authors: C
authors: C
authors: La Morgia
authors: From the Functional MR Unit (D.N.M., G.R., C.Tonon, C.Testa, R.L.).
authors: C
authors: C
authors: Tonon
authors: From the Functional MR Unit (D.N.M., G.R., C.Tonon, C.Testa, R.L.).
authors: C
authors: C
authors: Testa
authors: Studio Oculistico d'Azeglio (P.B.), Bologna, Italy.
authors: P
authors: P
authors: Barboni
authors: Department of Pharmacy and Biotechnology (E.M.), University of Bologna, Bologna, Italy.
authors: E
authors: E
authors: Malucelli
authors: Neurology Unit (G.R., C.L.M., M.L.V., L.C., D.S., V.C.), Department of Biomedical and NeuroMotor Sciences "Istituto di Ricovero e Cura a Carattere Scientifico Istituto delle Scienze Neurologiche di Bologna" (C.L.M., M.L.V., L.C., D.S., V.C.), Bologna, Italy.
authors: M L
authors: ML
authors: Valentino
authors: Neurology Unit (G.R., C.L.M., M.L.V., L.C., D.S., V.C.), Department of Biomedical and NeuroMotor Sciences "Istituto di Ricovero e Cura a Carattere Scientifico Istituto delle Scienze Neurologiche di Bologna" (C.L.M., M.L.V., L.C., D.S., V.C.), Bologna, Italy.
authors: L
authors: L
authors: Caporali
authors: Neurology Unit (G.R., C.L.M., M.L.V., L.C., D.S., V.C.), Department of Biomedical and NeuroMotor Sciences "Istituto di Ricovero e Cura a Carattere Scientifico Istituto delle Scienze Neurologiche di Bologna" (C.L.M., M.L.V., L.C., D.S., V.C.), Bologna, Italy.
authors: D
authors: D
authors: Strobbe
authors: Neurology Unit (G.R., C.L.M., M.L.V., L.C., D.S., V.C.), Department of Biomedical and NeuroMotor Sciences "Istituto di Ricovero e Cura a Carattere Scientifico Istituto delle Scienze Neurologiche di Bologna" (C.L.M., M.L.V., L.C., D.S., V.C.), Bologna, Italy raffaele.lodi@unibo.it valerio.carelli@unibo.it.
authors: V
authors: V
authors: Carelli
authors: From the Functional MR Unit (D.N.M., G.R., C.Tonon, C.Testa, R.L.) raffaele.lodi@unibo.it valerio.carelli@unibo.it.
authors: R
authors: R
authors: Lodi
mesh_terms: D000328:Adult; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D029241:Optic Atrophy, Autosomal Dominant / Q000473:pathology*; D029242:Optic Atrophy, Hereditary, Leber / Q000473:pathology*; D066127:White Matter / Q000473:pathology*