Neurological and neuroradiological alterations in OPA1-linked dominant optic atrophy patients

Abstract

Purpose: To describe clinical and neuroradiological features of patients with OPA1 mutations in order to delineate their morphological and functional brain abnormalities in relation with the presence or absence of an OPA1-plus clinical phenotype.

Methods: Twenty two patients from 17 families with decreased visual acuity related to optic atrophy and carrying an OPA1 mutation were enrolled. Neurological and ophthalmological examinations were done including peripapillary RNFL thickness assessment using optical coherence tomography (OCT). Brain magnetic resonance imaging (T1, T2 and flair sequences) was performed on a 1.5-Tesla MR Unit. Measurement of the chiasm width and height was performed on T1 coronal sections. Twenty among the 22 patients underwent 2-D proton spectroscopic imaging (MRS) performed with a point-resolved spectroscopy (PRESS) multivoxel sequence, as 15-mm of slice thickness localized in the bicommissural plane at the level of the central grey nuclei, or monovoxel sequence in the cerebellum.

Results: Neurological examination was normal in all but one patient who presented with a transient right hand motor deficit. Brain imaging disclosed abnormalities in 12 patients: aspecific white matter hypersignal (5 patients), cerebellar atrophy (5 patients), hemispheric cortical atrophy (1 patient), lactate peak (3 patients). Mean chiasmatic dimensions were significantly reduced compared to normal values, and chiasmatic width was below 2 SD in 7 patients. When comparing the group of patients with brain imaging abnormalities with that of patients with normal MRI, no difference was sorted out regarding age at onset, duration of the disease, severity of the visual deficit, dimensions of the chiasm, RNFL thickness assessed by OCT, or OPA1 mutation subtypes. All the patients with hearing loss had abnormal brain imaging findings.

Conclusions: Our results demonstrate that brain imaging abnormalities are common in patients harboring OPA1 mutation, even in those without neurological complain and normal neurological examination. Lactate peak and cerebellar atrophy are consistent with the mitochondrial dysfunction related to OPA1 mutations. Cortical atrophy and white matter hypersignal suggest that OPA1 mutations result in widespread neuronal degeneration.

Keywords: 613 neuro-ophthalmology: optic nerve • 600 mitochondria • 550 imaging/image analysis: clinical