title: Extra-ocular muscle MRI in genetically-defined mitochondrial disease.
abstract: OBJECTIVE
  Conventional and quantitative MRI was performed in patients with chronic progressive external ophthalmoplegia (CPEO), a common manifestation of mitochondrial disease, to characterise MRI findings in the extra-ocular muscles (EOMs) and investigate whether quantitative MRI provides clinically relevant measures of disease.
  
  
  METHODS
  Patients with CPEO due to single mitochondrial DNA deletions were compared with controls. Range of eye movement (ROEM) measurements, peri-orbital 3 T MRI T1-weighted (T1w) and short-tau-inversion-recovery (STIR) images, and T2 relaxation time maps were obtained. Blinded observers graded muscle atrophy and T1w/STIR hyperintensity. Cross-sectional areas and EOM mean T2s were recorded and correlated with clinical parameters.
  
  
  RESULTS
  Nine patients and nine healthy controls were examined. Patients had reduced ROEM (patients 13.3°, controls 49.3°, p < 0.001), greater mean atrophy score and increased T1w hyperintensities. EOM mean cross-sectional area was 43 % of controls and mean T2s were prolonged (patients 75.6 ± 7.0 ms, controls 55.2 ± 4.1 ms, p < 0.001). ROEM correlated negatively with EOM T2 (rho = -0.89, p < 0.01), whilst cross-sectional area failed to correlate with any clinical measures.
  
  
  CONCLUSIONS
  MRI demonstrates EOM atrophy, characteristic signal changes and prolonged T2 in CPEO. Correlation between elevated EOM T2 and ROEM impairment represents a potential measure of disease severity that warrants further evaluation.
  
  
  CONCLUSIONS
  Chronic progressive external ophthalmoplegia is a common clinical manifestation of mitochondrial disease. • Existing extra-ocular muscle MRI data in CPEO reports variable radiological findings. MRI confirmed EOM atrophy and characteristic signal changes in CPEO. EOM T2 was significantly elevated in CPEO and correlated negatively with ocular movements. EOM T2 represents a potential quantitative measure of disease severity in CPEO.
authors.affiliation: MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, UK. r.pitceathly@ucl.ac.uk.
authors.forename: Robert D S
authors.initials: RD
authors.lastname: Pitceathly
authors.affiliation: MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, UK.
authors.forename: Jasper M
authors.initials: JM
authors.lastname: Morrow
authors.affiliation: MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, UK.|Neuroradiological Academic Unit, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London, WC1N 3BG, UK.
authors.forename: Christopher D J
authors.initials: CD
authors.lastname: Sinclair
authors.affiliation: Neurogenetics Unit, National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, UK.
authors.forename: Cathy
authors.initials: C
authors.lastname: Woodward
authors.affiliation: Neurogenetics Unit, National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, UK.
authors.forename: Mary G
authors.initials: MG
authors.lastname: Sweeney
authors.affiliation: MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, UK.|Mitochondrial Research Group, Clinical and Molecular Genetics Unit, UCL Institute of Child Health, London, WC1N 1EH, UK.
authors.forename: Shamima
authors.initials: S
authors.lastname: Rahman
authors.affiliation: Department of Neuro-ophthalmology, National Hospital for Neurology and Neurosurgery, London, WC1N 3BG, UK.|Department of Neuro-ophthalmology, Moorfields Eye Hospital, London, EC1V 2PD, UK.
authors.forename: Gordon T
authors.initials: GT
authors.lastname: Plant
authors.affiliation: Department of Neuro-ophthalmology, National Hospital for Neurology and Neurosurgery, London, WC1N 3BG, UK.|Department of Neuro-ophthalmology, Moorfields Eye Hospital, London, EC1V 2PD, UK.
authors.forename: Nadeem
authors.initials: N
authors.lastname: Ali
authors.affiliation: Department of Neuro-ophthalmology, National Hospital for Neurology and Neurosurgery, London, WC1N 3BG, UK.
authors.forename: Fion
authors.initials: F
authors.lastname: Bremner
authors.affiliation: The Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, London, WC1N 3BG, UK.
authors.forename: Indran
authors.initials: I
authors.lastname: Davagnanam
authors.affiliation: MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, UK.|Neuroradiological Academic Unit, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London, WC1N 3BG, UK.
authors.forename: Tarek A
authors.initials: TA
authors.lastname: Yousry
authors.affiliation: MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, UK.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hanna
authors.affiliation: MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, UK.|Neuroradiological Academic Unit, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London, WC1N 3BG, UK.
authors.forename: John S
authors.initials: JS
authors.lastname: Thornton
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000150:complications* / Q000175:diagnosis / Q000235:genetics; D009801:Oculomotor Muscles / Q000473:pathology*; D017246:Ophthalmoplegia, Chronic Progressive External / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics; D055815:Young Adult
keywords: Chronic progressive external ophthalmoplegia; Kearns-Sayre syndrome; Magnetic resonance imaging; Mitochondrial DNA; Mitochondrial diseases