Laurike Harlaar1, Pierluigi Ciet2, Gijs van Tulder3, Alice Pittaro4, Harmke A van Kooten1, Nadine A M E van der Beek1, Esther Brusse1, Piotr A Wielopolski4, Marleen de Bruijne3,5, Ans T van der Ploeg6, Harm A W M Tiddens2, Pieter A van Doorn7. 1. Center for Lysosomal and Metabolic Diseases, Department of Neurology, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands. 2. Departments of Radiology and Nuclear Medicine, Paediatrics, and Respiratory Medicine and Allergology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. 3. Biomedical Imaging Group Rotterdam, Department of Radiology and Nuclear Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. 4. Department of Radiology and Nuclear Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. 5. Department of Computer Science, University of Copenhagen, Copenhagen, Denmark. 6. Center for Lysosomal and Metabolic Diseases, Department of Paediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. 7. Center for Lysosomal and Metabolic Diseases, Department of Neurology, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands. p.a.vandoorn@erasmusmc.nl.
Abstract
BACKGROUND: In Pompe disease, an inherited metabolic muscle disorder, severe diaphragmatic weakness often occurs. Enzyme replacement treatment is relatively ineffective for respiratory function, possibly because of irreversible damage to the diaphragm early in the disease course. Mildly impaired diaphragmatic function may not be recognized by spirometry, which is commonly used to study respiratory function. In this cross-sectional study, we aimed to identify early signs of diaphragmatic weakness in Pompe patients using chest MRI. METHODS: Pompe patients covering the spectrum of disease severity, and sex and age matched healthy controls were prospectively included and studied using spirometry-controlled sagittal MR images of both mid-hemidiaphragms during forced inspiration. The motions of the diaphragm and thoracic wall were evaluated by measuring thoracic cranial-caudal and anterior-posterior distance ratios between inspiration and expiration. The diaphragm shape was evaluated by measuring the height of the diaphragm curvature. We used multiple linear regression analysis to compare different groups. RESULTS: We included 22 Pompe patients with decreased spirometry results (forced vital capacity in supine position < 80% predicted); 13 Pompe patients with normal spirometry results (forced vital capacity in supine position ≥ 80% predicted) and 18 healthy controls. The mean cranial-caudal ratio was only 1.32 in patients with decreased spirometry results, 1.60 in patients with normal spirometry results and 1.72 in healthy controls (p < 0.001). Anterior-posterior ratios showed no significant differences. The mean height ratios of the diaphragm curvature were 1.41 in patients with decreased spirometry results, 1.08 in patients with normal spirometry results and 0.82 in healthy controls (p = 0.001), indicating an increased curvature of the diaphragm during inspiration in Pompe patients. CONCLUSIONS: Even in early-stage Pompe disease, when spirometry results are still within normal range, the motion of the diaphragm is already reduced and the shape is more curved during inspiration. MRI can be used to detect early signs of diaphragmatic weakness in patients with Pompe disease, which might help to select patients for early intervention to prevent possible irreversible damage to the diaphragm.
BACKGROUND: In Pompe disease, an inherited metabolic muscle disorder, severe diaphragmatic weakness often occurs. Enzyme replacement treatment is relatively ineffective for respiratory function, possibly because of irreversible damage to the diaphragm early in the disease course. Mildly impaired diaphragmatic function may not be recognized by spirometry, which is commonly used to study respiratory function. In this cross-sectional study, we aimed to identify early signs of diaphragmatic weakness in Pompe patients using chest MRI. METHODS: Pompe patients covering the spectrum of disease severity, and sex and age matched healthy controls were prospectively included and studied using spirometry-controlled sagittal MR images of both mid-hemidiaphragms during forced inspiration. The motions of the diaphragm and thoracic wall were evaluated by measuring thoracic cranial-caudal and anterior-posterior distance ratios between inspiration and expiration. The diaphragm shape was evaluated by measuring the height of the diaphragm curvature. We used multiple linear regression analysis to compare different groups. RESULTS: We included 22 Pompe patients with decreased spirometry results (forced vital capacity in supine position < 80% predicted); 13 Pompe patients with normal spirometry results (forced vital capacity in supine position ≥ 80% predicted) and 18 healthy controls. The mean cranial-caudal ratio was only 1.32 in patients with decreased spirometry results, 1.60 in patients with normal spirometry results and 1.72 in healthy controls (p < 0.001). Anterior-posterior ratios showed no significant differences. The mean height ratios of the diaphragm curvature were 1.41 in patients with decreased spirometry results, 1.08 in patients with normal spirometry results and 0.82 in healthy controls (p = 0.001), indicating an increased curvature of the diaphragm during inspiration in Pompe patients. CONCLUSIONS: Even in early-stage Pompe disease, when spirometry results are still within normal range, the motion of the diaphragm is already reduced and the shape is more curved during inspiration. MRI can be used to detect early signs of diaphragmatic weakness in patients with Pompe disease, which might help to select patients for early intervention to prevent possible irreversible damage to the diaphragm.
Authors: M J Guimarães; J C Winck; B Conde; A Mineiro; M Raposo; J Moita; A Marinho; J M Silva; N Pires; S André; C Loureiro Journal: Rev Port Pneumol (2006) Date: 2017-05-09
Authors: L Harlaar; P Ciet; A T van der Ploeg; E Brusse; N A M E van der Beek; P A Wielopolski; M de Bruijne; H A W M Tiddens; P A van Doorn Journal: Neuromuscul Disord Date: 2017-11-24 Impact factor: 4.296
Authors: Ans T van der Ploeg; Paula R Clemens; Deyanira Corzo; Diana M Escolar; Julaine Florence; Geert Jan Groeneveld; Serge Herson; Priya S Kishnani; Pascal Laforet; Stephen L Lake; Dale J Lange; Robert T Leshner; Jill E Mayhew; Claire Morgan; Kenkichi Nozaki; Dorothy J Park; Alan Pestronk; Barry Rosenbloom; Alison Skrinar; Carine I van Capelle; Nadine A van der Beek; Melissa Wasserstein; Sasa A Zivkovic Journal: N Engl J Med Date: 2010-04-15 Impact factor: 91.245
Authors: C Angelini; C Semplicini; S Ravaglia; B Bembi; S Servidei; E Pegoraro; M Moggio; M Filosto; E Sette; G Crescimanno; P Tonin; R Parini; L Morandi; G Marrosu; G Greco; O Musumeci; G Di Iorio; G Siciliano; M A Donati; F Carubbi; M Ermani; T Mongini; A Toscano Journal: J Neurol Date: 2011-11-12 Impact factor: 4.849
Authors: Hannerieke M P van den Hout; Wim Hop; Otto P van Diggelen; Jan A M Smeitink; G Peter A Smit; Bwee-Tien T Poll-The; Henk D Bakker; M Christa B Loonen; Johannis B C de Klerk; Arnold J J Reuser; Ans T van der Ploeg Journal: Pediatrics Date: 2003-08 Impact factor: 7.124
Authors: Erin M Johnson; Mark Roberts; Tahseen Mozaffar; Peter Young; Adrian Quartel; Kenneth I Berger Journal: Neuromuscul Disord Date: 2015-11-30 Impact factor: 4.296
Authors: Laurike Harlaar; Jean-Yves Hogrel; Barbara Perniconi; Michelle E Kruijshaar; Dimitris Rizopoulos; Nadjib Taouagh; Aurélie Canal; Esther Brusse; Pieter A van Doorn; Ans T van der Ploeg; Pascal Laforêt; Nadine A M E van der Beek Journal: Neurology Date: 2019-10-16 Impact factor: 9.910