White Matter Microstructure Abnormalities in Patients with Dominant Optic Atrophy and OPA1 Mutations (S39.002)

OBJECTIVE: Aim of this study was to assess abnormalities of white matter (WM) microstructure in patients affected by dominant optic atrophy (DOA) linked to OPA1 gene mutations, using tract-based spatial statistics (TBSS) analysis. BACKGROUND: The OPA1 gene is involved in mithocondrial respiratory functions and cellular protection from apoptosis. Its transcripts are highly expressed not only in the retina, but also in the brain. Patients with DOA typically present a slowly progressive, painless, bilateral visual loss. Extra-ocular neurological complications affect up to 20% of all mutational carriers. DESIGN/METHODS: Using a 3.0 Tesla scanner, dual-echo and diffusion tensor (DT) MRI images were derived from 19 patients with DOA (10 females, mean age=43 years, range=22-64) and 20 sex- and age-matched controls . A complete neurological and neuro-ophthalmologic examination was obtained in all patients. TBSS analysis was performed using FMRIB's Diffusion Toolbox. RESULTS: Visual acuity was reduced in almost all patients, whereas none of the patients had extra-ocular neurological complications. Focal lesions in the brain WM were identified in ten patients. Three patients presented hyperintense optic nerve lesions on T2 weighted scans. Optic nerve and chiasm atrophy were detected in twelve patients. TBSS analysis showed that compared to controls, patients with DOA had significant lower mean diffusivity, axial and radial diffusivity in WM of the cerebellum, brainstem, thalamus, fronto-occipital-temporal lobes, including the cingulum, corpus callosum, corticospinal tract and optic radiation bilaterally. No abnormalities of fractional anisotropy were detected. DT MRI measures were correlate with ganglion cell complex thickness. CONCLUSIONS: Patients with DOA linked to OPA1 gene mutations present diffuse WM microstructural abnormalities. Clinical expression of DOA could be influenced by the level of mithocondrial impairment and potential compensatory mechanisms, such as increased protein expression. Restricted water diffusion might be explained by a higher macromolecular water binding, due to increased molecular crowding and microviscosity. Study Supported by: