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Lookup NU author(s): Dr Cynthia Yu Wai Man, Dr Fiona Smith, Dr Michael FirbankORCiD, Professor Grainne Gorman, Professor Robert Taylor, Emeritus Professor Doug Turnbull, Philip Griffiths, Professor Andrew BlamireORCiD, Professor Patrick Chinnery, Dr Patrick Yu Wai Man
Background: Chronic progressive external ophthalmoplegia (CPEO) is a classical mitochondrial ocular disorder characterised by bilateral progressive ptosis and ophthalmoplegia. These ocular features can develop either in isolation or in association with other prominent neurological deficits (CPEO+). Molecularly, CPEO can be classified into two distinct genetic subgroups depending on whether patients harbour single, large-scale mitochondrial DNA (mtDNA) deletions or multiple mtDNA deletions secondary to a nuclear mutation disrupting mtDNA replication or repair. The aim of this magnetic resonance imaging (MRI) study was to investigate whether the ophthalmoplegia in CPEO is primarily myopathic in origin or whether there is evidence of contributory supranuclear pathway dysfunction.Methods: Ten age-matched normal controls and twenty patients with CPEO were recruited nine patients with single, large-scale mtDNA deletions and eleven patients with multiple mtDNA deletions secondary to mutations in POLG, PEO1, OPA1, and RRM2B. All subjects underwent a standardised brain and orbital MRI protocol, together with proton magnetic resonance spectroscopy in two voxels located within the parietal white matter and the brainstem.Results: There was evidence of significant extraocular muscle atrophy in patients with single or multiple mtDNA deletions compared with controls. There was no significant difference in metabolite concentrations between the patient and control groups in both the parietal white matter and brainstem voxels. Volumetric brain measurements revealed marked cortical and cerebellar atrophy among patients with CPEO+ phenotypes.Conclusion: The results of this study support a primary myopathic aetiology for the progressive limitation of eye movements that develops in CPEO.
Author(s): Yu-Wai-Man C, Smith FE, Firbank MJ, Guthrie G, Guthrie S, Gorman GS, Taylor RW, Turnbull DM, Griffiths PG, Blamire AM, Chinnery PF, Yu-Wai-Man P
Publication type: Article
Publication status: Published
Journal: PLoS ONE
Year: 2013
Volume: 8
Issue: 9
Online publication date: 27/09/2013
Acceptance date: 07/08/2013
Date deposited: 05/01/2015
ISSN (electronic): 1932-6203
Publisher: Public Library of Science
URL: http://dx.doi.org/10.1371/journal.pone.0075048
DOI: 10.1371/journal.pone.0075048
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