Visual Pathway Functional and Structural Abnormalities in Leber’s Hereditary Optic Neuropathy (LHON)

Abstract

Purpose: : To evaluate in patients with LHON a) brain gray matter (GM) and white matter (WM) damage using structural MRI (diffusion tensor, DT tractography and Voxel Based Morphometry, VBM); b) brain activations using visual stimulation and functional MRI (fMRI); c) correlations between fMRI activations and measures of structural damage along the visual pathways; d) correlations between functional and structural MRI findings with neuro-ophthalmologic and OCT RNFL data.

Methods: : Using a 3.0 Tesla scanner, dual-echo, 3D fast-field echo, DT MRI and fMRI during 5 different visual stimulations were acquired from 16 LHON patients (mean age 31.2, range 21-61 years) and 12 age-sex matched controls. All subjects underwent neuro-ophthalmologic examination and OCT RNFL analysis. VBM analysis was performed using SPM5 and ANCOVA model. Statistical parametric mapping (SPM5) software was used to perform fMRI analyses; tractography analysis was performed using FDT toolbox (FSL library).

Results: : VBM analysis showed that LHON patients had significant clusters of reduced WM volume in the chiasm, optic tracts and in several areas of the optic radiations (OR). V1 atrophy was significantly correlated with average and temporal RNFL thicknesses. OR atrophy was significantly correlated with disease duration, and average and temporal RNFL thicknesses. DT tractography analysis demonstrated abnormal metrics in the right optic radiation and reduced fractional anisotropy (FA) of the connection between the left lateral geniculate body and V5 which were significantly correlated with RNFL measurements. Significant reduction of V1 activation was found bilaterally, as well as increased activation of the right V5.

Conclusions: : Central nervous system (CNS) involvement in LHON extends posteriorly to the OR and V1, probably through trans-synaptic degeneration. The activation of V5 could be interpreted as a possible compensatory mechanism secondary to V1 damage. LHON might represent a valuable model to study the effect of axonal loss in the CNS.

Keywords: neuro-ophthalmology: optic nerve • imaging/image analysis: clinical • nerve fiber layer