White and Gray Matter Damage Extends beyond the Visual Pathways in Patients with Autosomal Dominant Optic Atrophy and OPA1 Mutations (P07.265)

Abstract

Objective: To assess the patterns of regional atrophy in the brain gray matter (GM) and white matter (WM) in patients affected by autosomal dominant optic atrophy (DOA) linked to OPA1 gene mutations, using voxel-based morphometry (VBM). Background Patients with DOA typically present a slowly progressive, painless, bilateral visual loss, in the first two decades of life. Extra-ocular neurological complications affect up to 20% of all mutational carriers and may include sensorineural deafness, ataxia, myopathy, peripheral neuropathy, external ophthalmoplegia, spastic paraparesis and a multiple sclerosis-like illness. Design/Methods: We studied 8 patients with DOA and 20 healthy controls. A complete neuro-ophthalmologic examination, including 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 RNFL 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. Disclosure: Dr. Messina has nothing to disclose. Ms. Rocca has received personal compensation for activities with Bayer Schering Pharma and Biogen Idec as a consultant. Dr. Bianchi Marzoli has nothing to disclose. Dr. Milesi has nothing to disclose. Dr. Petrolini has nothing to disclose. Dr. Falini has nothing to disclose. Dr. Comi has received personal compensation for activities with Novartis, Teva Neuroscience, Sanofi-Aventis Pharmaceuticals, Inc., Merck Serono, Bayer Schering, and Biogen Dompe. Dr. Filippi has received personal compensation for activities with ECTRIMS, MSIF, MS Ireland, US NMSS, Bayer-Schering, Biogen-Dompe AG, Genmab, Merck Serono, Pepgen Corporation, Teva, and Sanofi-Aventis. Dr. Filippi has received research support from Teva, Bayer-Schering and Genmab.