Chronic Progressive External Ophthalmoplegia: MR Spectroscopy and MR Diffusion Studies in the Brain

Abstract

The purpose of our study was to show how, despite pathognomonic signs of cerebral involvement in chronic progressive external ophthalmoplegia (CPEO), mitochondrial respiratory chain insufficiency is associated with increased lactate and reduced N-acetylaspartate. CPEO and mitochondrial myopathy are caused by mitochondrial DNA mutations leading to impaired oxidative phosphorylation. Cortical and subcortical metabolites, cerebral diffusivity, and structural MRI were assessed to characterize possible subclinical cerebral pathology in CPEO. Ten patients with CPEO (n = 8), mitochondrial myopathy (n = 1), and Kearns-Sayre syndrome (n = 1) and 13 control group volunteers were studied by MRI, both long TE (144) proton MR spectroscopic imaging (1H MRSI), and diffusion-weighted imaging. Relative concentrations of N-acetylaspartate, choline, creatine, and lactate were estimated by Linear Combination of Model Spectra (LCModel) in healthy-appearing white matter, gray matter, and white matter hyperintensities. Of five patients with cortical atrophy, it was moderate in three and severe in two. One patient had severe and four had moderate cerebellar atrophy. Six of 10 patients showed unspecific white matter lesions, whereas the remainder had hyperintensities in the pyramidal tract (n =2) and middle cerebellar peduncle (n = 1) despite clinical signs. No basal ganglia lesions were found. Physiologic metabolite ratios were normal and lactate was absent in supratentorial healthy-appearing cortex and subcortical white matter. Global diffusion histogram metrics revealed no abnormalities. Normal spectroscopic imaging in radiologic unaffected brain and healthy global brain parenchymal diffusion findings do not support the hypothesis of a generalized cerebral energy loss in CPEO. Bilateral structural alteration of central motor pathways in two patients without clinical pyramidal signs may, however, reflect subclinical axonal injury in predilection sites in some patients.