Chest MRI to diagnose early diaphragmatic weakness in Pompe disease

Orphanet J Rare Dis 2021 Jan 7;16(1):21. doi: 10.1186/s13023-020-01627-x.

PMID: 33413525

Laurike Harlaar, Pierluigi Ciet, Gijs van Tulder

Highlights: In this cross-sectional study, it is aimed to identify early signs of diaphragmatic weakness in Pompe patients using chest MRI.

Abstract

Background: Severe diaphragmatic weakness is common in Pompe disease, an inherited metabolic muscle disorder. Because of irreversible damage to the diaphragm early in the disease course, enzyme replacement therapy is relatively ineffectual for respiratory function. Spirometry, which is routinely used to assess respiratory function, may not detect mildly decreased diaphragmatic function. We used chest MRI to identify early symptoms of diaphragmatic weakness in Pompe patients in this cross-sectional investigation.

Methods: Patients with Pompe disease ranging from mild to severe, as well as sex and age matched healthy controls, were investigated utilizing spirometry-controlled sagittal MR images of both mid-hemidiaphragms during forced inspiration. Measurements of thoracic cranial-caudal and anterior-posterior distance ratios between inspiration and expiration were used to assess diaphragm and thoracic wall motions. The height of the diaphragm curvature was used to assess the diaphragm curvature. To compare the different groups, we utilized multiple linear regression analysis.

Results: 22 Pompe patients with decreased spirometry findings (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 were included in the study. The mean cranial-caudal ratio was only 1.32 in patients with low spirometry findings, 1.60 in healthy controls, and 1.72 in patients with normal spirometry results (p < 0.001). There were no significant variations in anterior-posterior ratios. The mean height ratios of the diaphragm curvature were 1.41 in patients with decreased spirometry findings, 1.08 in patients with normal spirometry results, and 0.82 in healthy controls (p = 0.001), showing that the diaphragm curvature in Pompe patients was increased during inspiration.

Conclusions: The mobility of the diaphragm is already diminished and the form is more curved during inspiration in early-stage Pompe illness, while spirometry findings are still within normal range. In individuals with Pompe disease, MRI can be utilized to detect early indicators of diaphragmatic weakening, which may aid in the selection of patients for early treatments to avoid irreversible diaphragmatic damage.

Keywords: Diaphragm, Lysosomal storage disease, MRI, Neuromuscular disease, Pompe disease, Respiratory function