Lung MRI and impairment of diaphragmatic function in Pompe disease

Stephan CA Wens, Pierluigi Ciet, Adria Perez-Rovira, Karla Logie, Elizabeth Salamon, Piotr Wielopolski, Marleen de Bruijne, Michelle E Kruijshaar, Harm AWM Tiddens, Pieter A van Doorn, Ans T van der Ploeg

Pompe disease is a progressive metabolic myopathy. Involvement of respiratory muscles leads to progressive pulmonary dysfunction, particularly in supine position. Diaphragmatic weakness is considered to be the most important component. Standard spirometry is to some extent indicative but provides too little insight into diaphragmatic dynamics. We used lung MRI to study diaphragmatic and chest-wall movements in Pompe disease. In ten adult Pompe patients and six volunteers, we acquired two static spirometer-controlled MRI scans during maximum inspiration and expiration. Images were manually segmented. After normalization for lung size, changes in lung dimensions between inspiration and expiration were used for analysis; normalization was based on the cranial-caudal length ratio (representing vertical diaphragmatic displacement), and the anterior-posterior and left-right length ratios (representing chest-wall movements due to thoracic muscles). We observed striking dysfunction of the diaphragm in Pompe patients; in some patients the diaphragm did not show any displacement. Patients had smaller cranial-caudal length ratios than volunteers (p < 0.001), indicating diaphragmatic weakness. This variable strongly correlated with forced vital capacity in supine position (r = 0.88) and postural drop (r = 0.89). While anterior-posterior length ratios also differed between patients and volunteers (p = 0.04), left-right length ratios did not (p = 0.1). MRI is an innovative tool to visualize diaphragmatic dynamics in Pompe patients and to study chest-wall and diaphragmatic movements in more detail. Our data indicate that diaphragmatic displacement may be severely disturbed in patients with Pompe disease.