title: Patterns of white matter diffusivity abnormalities in Leber's hereditary optic neuropathy: a tract-based spatial statistics study.
abstract: Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease characterized by retinal ganglion cell degeneration and optic nerve atrophy, leading to a loss of central vision. The aim of this study was to explore the topographical pattern of damage to the brain white matter (WM) tracts from patients with chronic LHON using diffusion tensor (DT) MRI and tract-based spatial statistics (TBSS). Brain dual-echo and DT MRI scans were acquired from 13 patients with chronic LHON and 25 matched controls using a 3.0 T scanner. TBSS analysis was performed using the FMRIB's Diffusion Toolbox. A complete neuro-ophthalmologic examination, including standardized automated Humphrey perimetry as well as average and temporal peripapillary retinal nerve fiber layer thickness (PRNFL) measurements, was obtained in all patients. Mean average and temporal PRNFL thicknesses were decreased significantly in LHON patients. Compared to controls, TBSS analysis revealed significant diffusivity abnormalities in these patients, which were characterized by a decreased fractional anisotropy (FA) and an increased mean diffusivity and radial diffusivity, affecting exclusively the optic tracts and optic radiations (OR). In patients, a significant correlation was found between optic tract average FA and mean visual acuity (r = 0.57, p = 0.04). In LHON patients, DT MRI reveals a microstructural alteration of the WM along the entire visual pathways, with a sparing of the other main WM tracts of the brain. Damage to the OR may be secondary either to trans-synaptic degeneration, which in turn is due to neuroaxonal loss in the retina and optic nerve, or to local mitochondrial dysfunction.
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Jacopo
authors.initials: J
authors.lastname: Milesi
authors.forename: Maria A
authors.initials: MA
authors.lastname: Rocca
authors.forename: Stefania
authors.initials: S
authors.lastname: Bianchi-Marzoli
authors.forename: Melissa
authors.initials: M
authors.lastname: Petrolini
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Pagani
authors.forename: Andrea
authors.initials: A
authors.lastname: Falini
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
mesh_terms: D000328:Adult; D016880:Anisotropy; D001921:Brain / Q000473:pathology*; D016022:Case-Control Studies; D003943:Diagnostic Techniques, Neurological; D003941:Diagnostic Techniques, Ophthalmological; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D029242:Optic Atrophy, Hereditary, Leber / Q000473:pathology*; D013223:Statistics as Topic; D041623:Tomography, Optical Coherence / Q000379:methods; D014794:Visual Fields / Q000502:physiology; D055815:Young Adult