Regional Patterns of Brain Gray and White Matter Abnormalities in Patients with Hereditary Optic Neuropathies: Dominant Optic Atrophy <i>vs</i> Leber Hereditary Optic Neuropathy (S48.006)

Objective: To compare the regional patterns of gray matter (GM) and white matter (WM) abnormalities between patients with Dominant Optic Atrophy (DOA) and Leber Hereditary Optic Neuropathy (LHON), using voxel-wise methods. Background: Previous studies revealed an involvement of the whole visual pathway in patients with LHON, whereas DOA patients had tissue loss of the anterior optic pathway and distributed brain WM microstructural abnormalities. Methods: Using a 3.0 Tesla scanner, 3D T1-weighted and diffusion tensor images were derived from 16 patients with LHON, 19 patients with DOA and 20 controls. VBM was performed using SPM8. TBSS analysis was performed using FMRIB's Diffusion Toolbox. Results: VBM analysis showed that, compared to controls, LHON and DOA patients had reduced WM volume of the optic chiasm and optic tracts. LHON patients had also atrophy of the left optic radiations (OR) compared to controls and DOA patients as well as reduced left primary visual cortex volume compared to controls. At TBSS analysis, compared to controls, LHON patients had only decreased fractional anisotropy (FA) and increased mean diffusivity (MD) and radial diffusivity (RD) of the OR. Compared to controls and LHON, DOA patients had lower MD, RD and axial diffusivity (AD) in the WM of the cerebellum, brainstem, thalamus and fronto-occipital-temporal lobes. No FA abnormalities were detected in DOA patients. Conclusions: We confirmed that both LHON and DOA patients had an involvement of the anterior visual pathways. However, in LHON patients, structural damage extends to the posterior optic pathways with a sparing of other brain regions, whereas in DOA patients there is a more diffuse WM damage. All of this suggests that different molecular defects and genetic inheritance might lead to different pattern of structural brain abnormalities in patients with hereditary optic neuropathies.