title: Quantitative magnetic resonance imaging in limb-girdle muscular dystrophy 2I: a multinational cross-sectional study.
abstract: We conducted a prospective multinational study of muscle pathology using magnetic resonance imaging (MRI) in patients with limb-girdle muscular dystrophy 2I (LGMD2I). Thirty eight adult ambulant LGMD2I patients (19 male; 19 female) with genetically identical mutations (c.826C>A) in the fukutin-related protein (FKRP) gene were recruited. In each patient, T1-weighted (T1w) imaging was assessed by qualitative grading for 15 individual lower limb muscles and quantitative Dixon imaging was analysed on 14 individual lower limb muscles by region of interest analysis. We described the pattern and appearance of muscle pathology and gender differences, not previously reported for LGMD2I. Diffuse fat infiltration of the gastrocnemii muscles was demonstrated in females, whereas in males fat infiltration was more prominent in the medial than the lateral gastrocnemius (p = 0.05). In the anterior thigh of males, in contrast to females, median fat infiltration in the vastus medialis muscle (45.7%) exceeded that in the vastus lateralis muscle (11.2%) (p<0.005). MRI is non-invasive, objective and does not rely on patient effort compared to clinical and physical measures that are currently employed. We demonstrated (i) that the quantitative Dixon technique is an objective quantitative marker of disease and (ii) new observations of gender specific patterns of muscle involvement in LGMD2I.
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom ; The Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, Shropshire, United Kingdom.
authors.forename: Tracey A
authors.initials: TA
authors.lastname: Willis
authors.affiliation: Newcastle Magnetic Resonance Centre, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Kieren G
authors.initials: KG
authors.lastname: Hollingsworth
authors.affiliation: Newcastle Magnetic Resonance Centre, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Anna
authors.initials: A
authors.lastname: Coombs
authors.affiliation: Neuromuscular Research Unit, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Sveen
authors.affiliation: Neuromuscular Research Unit, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Soren
authors.initials: S
authors.lastname: Andersen
authors.affiliation: Centre de Reference des Maladies Neuromusculaires Paris Est, Institut de Myologie Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
authors.forename: Tanya
authors.initials: T
authors.lastname: Stojkovic
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Michelle
authors.initials: M
authors.lastname: Eagle
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Anna
authors.initials: A
authors.lastname: Mayhew
authors.affiliation: Institut de Myologie Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
authors.forename: Paulo Loureiro
authors.initials: PL
authors.lastname: de Sousa
authors.affiliation: MRC Centre for Neuromuscular Diseases, Department of Molecular Neurosciences, UCL Institute of Neurology, London, United Kingdom.
authors.forename: Liz
authors.initials: L
authors.lastname: Dewar
authors.affiliation: MRC Centre for Neuromuscular Diseases, Department of Molecular Neurosciences, UCL Institute of Neurology, London, United Kingdom.
authors.forename: Jasper M
authors.initials: JM
authors.lastname: Morrow
authors.affiliation: MRC Centre for Neuromuscular Diseases, Department of Molecular Neurosciences, UCL Institute of Neurology, London, United Kingdom.
authors.forename: Christopher D J
authors.initials: CD
authors.lastname: Sinclair
authors.affiliation: MRC Centre for Neuromuscular Diseases, Department of Molecular Neurosciences, UCL Institute of Neurology, London, United Kingdom.
authors.forename: John S
authors.initials: JS
authors.lastname: Thornton
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Kate
authors.initials: K
authors.lastname: Bushby
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Hanns
authors.initials: H
authors.lastname: Lochmuller
authors.affiliation: MRC Centre for Neuromuscular Diseases, Department of Molecular Neurosciences, UCL Institute of Neurology, London, United Kingdom.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hanna
authors.affiliation: Institut de Myologie Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Hogrel
authors.affiliation: Institut de Myologie Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
authors.forename: Pierre G
authors.initials: PG
authors.lastname: Carlier
authors.affiliation: Neuromuscular Research Unit, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: John
authors.initials: J
authors.lastname: Vissing
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Volker
authors.initials: V
authors.lastname: Straub
mesh_terms: D052436:Adipose Tissue, White / Q000378:metabolism / Q000473:pathology*; D000293:Adolescent; D000328:Adult; D003430:Cross-Sectional Studies; D005060:Europe; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology*; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics / Q000473:pathology*; D009154:Mutation; D010430:Pentosyltransferases; D011506:Proteins / Q000235:genetics*; D012737:Sex Factors
chemical_list: D011506:Proteins; C443107:FKRP protein, human; D010430:Pentosyltransferases