White And Gray Matter Damage Extends Beyond The Visual Pathways In Patients With Autosomal Dominant Optic Atrophy And Opa1 Mutations

Abstract

Purpose: : To assess the patterns of regional atrophy in the brain gray matter (GM) and white matter (WM) of patients affected by autosomal dominant optic atrophy (DOA) linked to OPA1 gene mutations, using voxel-based morphometry (VBM).

Methods: : We studied 8 patients with DOA and 20 healthy controls. A complete neuro-ophthalmologic examination, including automated standardized perimetry (Humphrey Zeiss, 30-2 SITA standard), average retinal nerve fiber layer thickness (RNFL) and ganglion cell complex (GCC) measurements, was obtained in all patients. VBM was performed on the 3D T1-weighted images using SPM8 and DARTEL.

Results: : Average GCC and PRNFL thicknesses were decreased significantly in DOA patients. Focal lesions in the brain WM were identified in 2 patients. Optic nerve and chiasm atrophy were detected in four patients. Compared with controls, DOA patients showed a significant WM loss in the optic tracts. They also had GM loss in several regions located in the occipital lobes (including the lingual gyrus and superior occipital gyrus), the temporal lobes (including the auditory cortex), and the left precentral gyrus.

Conclusions: : In DOA patients carrying OPA1 mutations, structural abnormalities are present in the central nervous system. Such a damage is not limited to the anterior and posterior visual pathways, possibly due to trans-synaptic degeneration phenomena, but also involves the auditory and the motor cortices, probably due to local mitochondrial dysfunction.

Keywords: optic nerve • imaging/image analysis: clinical • visual impairment: neuro-ophthalmological disease