15 research outputs found
Long-term follow-up of 17 patients with childhood Pompe disease treated with enzyme replacement therapyKeywords
Get PDFMRI changes in diaphragmatic motion and curvature in Pompe disease over time
Get PDFOBJECTIVES: To evaluate changes in diaphragmatic function in Pompe disease using MRI over time, both during natural disease course and during treatment with enzyme replacement therapy (ERT). METHODS: In this prospective study, 30 adult Pompe patients and 10 healthy controls underwent pulmonary function tests and spirometry-controlled MRI twice, with an interval of 1 year. In the sagittal view of 3D gradient echo breath-hold acquisitions, diaphragmatic motion (cranial-caudal ratio between end-inspiration and end-expiration) and curvature (diaphragm height and area ratio) were calculated using a machine learning algorithm based on convolutional neural networks. Changes in outcomes after 1 year were compared between Pompe patients and healthy controls using the Mann-Whitney test. RESULTS: Pulmonary function outcomes and cranial-caudal ratio in Pompe patients did not change significantly over time compared to healthy controls. Diaphragm height ratio increased by 0.04 (−0.38 to 1.79) in Pompe patients compared to −0.02 (−0.18 to 0.25) in healthy controls (p = 0.02). An increased diaphragmatic curvature over time was observed in particular in untreated Pompe patients (p = 0.03), in those receiving ERT already for over 3 years (p = 0.03), and when severe diaphragmatic weakness was found on the initial MRI (p = 0.01); no progression was observed in Pompe patients who started ERT less than 3 years ago and in Pompe patients with mild diaphragmatic weakness on their initial MRI. CONCLUSIONS: MRI enables to detect small changes in diaphragmatic curvature over 1-year time in Pompe patients. It also showed that once severe diaphragmatic weakness has occurred, improvement of diaphragmatic muscle function seems unlikely. KEY POINTS: • Changes in diaphragmatic curvature in Pompe patients over time assessed with 3D MRI may serve as an outcome measure to evaluate the effect of treatment on diaphragmatic function. • Diaphragmatic curvature showed a significant deterioration after 1 year in Pompe patients compared to healthy controls, but the curvature seems to remain stable over this period in patients who were treated with enzyme replacement therapy for less than 3 years, possibly indicating a positive effect of ERT. • Improvement of diaphragmatic curvature over time is rarely seen in Pompe patients once diaphragmatic motion shows severe impairment (cranial-caudal inspiratory/expiratory ratio < 1.4). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00330-022-08940-y
Utility of language comprehension tests for unintelligible or non-speaking children with cerebral palsy: a systematic review
No full textUtility of language comprehension tests for unintelligible or non-speaking children with cerebral palsy: a systematic review
No full textLarge variation in effects during 10 years of enzyme therapy in adults with Pompe disease
No full textPositive association between physical outcomes and patient-reported outcomes in late-onset Pompe disease: a cross sectional study
Get PDFBACKGROUND: Pompe disease is a rare, progressive metabolic myopathy. The aim of this study is to investigate the associations of physical outcomes with patient-reported outcome measures (PROMs) in late-onset Pompe disease. METHODS: We included 121 Dutch adult patients with Pompe disease. Physical outcomes comprised muscle strength (manual muscle testing using Medical Research Council [MRC] grading, hand-held dynamometry [HHD]), walking ability (6-min walk test [6MWT]), and pulmonary function (forced vital capacity [FVC] in upright and supine positions). PROMs comprised quality of life (Short Form 36 health survey [SF-36]), participation (Rotterdam Handicap Scale [RHS]) and daily-life activities (Rasch-Built Pompe-Specific Activity [R-PAct] Scale). Analyses were cross-sectional: the time-point before, and closest to, start of Enzyme Replacement Therapy was chosen. Associations between PROMs and physical outcomes were investigated using linear regression models. RESULTS: RHS and R-PAct scores were better in patients with higher FVC supine and upright, HHD, MRC and 6MWT scores, accounting for the effect of sex, disease duration, use of wheelchair and ventilator support. While the SF-36 Physical Component Summary (PCS) was correlated positively with FVC upright, HHD, MRC and 6MWT scores, there was no significant relationship between the SF-36 Mental Component Summary (MCS) and any of the physical outcomes. CONCLUSIONS: Participation, daily-life activities, and the physical component of quality of life of adult Pompe patients are positively correlated to physical outcomes. This work serves as a first step towards assessing how changes over time in physical outcomes are related to changes in PROMs, and to define the minimal change in physical outcomes required to make an important difference for the patient
Distal muscle weakness is a common and early feature in long-term enzyme-treated classic infantile Pompe patients
Get PDFBackground: Enzyme replacement therapy (ERT; alglucosidase alfa) has improved the prospects for patients with
classic infantile Pompe disease considerably. However, over time we noticed that many of these children exhibit
distal muscle weakness at an early age, which is in contrast to the primarily proximal and axial muscle weakness in
patients with late-onset Pompe disease. This was reason to study the prevalence and severity of distal muscle
weakness, and the sequence of muscle involvement over time in patients that had learned to walk under ERT.
Methods: In this prospective, single-center cohort study, we studied 16 classic infantile patients. We used video
recordings that were made during regular standardized assessments to investigate distal muscle function (active
dorsiflexion of the feet during walking; ability to use a pincer grasp/actively extend the fingers) and proximal
muscle function (standing up from a supine position; raising the arms above the head).
Results: Median age at start of ERT was 3.2 months (0.1–5.8 months), median age at study end was 5.6 years (2.9–
18.2 years). Six patients (6/16, 38%) initially had no evident signs of distal muscle weakness and developed a gait
with active dorsiflexion of the feet. The other 10 patients never exhibited active dorsiflexion of the feet during
walking. At study-end two patients showed no loss of distal muscle function. A subset of five patients (5/16, 31%)
developed also weakness of the hands, particularly of the extensors of the 3rd and 4th digit.
Conclusions: We found that the majority (14/16, 88%) of patients who had learned to walk exhibited distal muscle
weakness of the lower extremities, while a subset (5/16, 31%) also developed weakness of the hands. The distal
muscle weakness was often more serious than, and preceded the development of, the proximal muscle weakness
Imaging of respiratory muscles in neuromuscular disease:A review
No full textRespiratory muscle weakness frequently occurs in patients with neuromuscular disease. Measuring respiratory function with standard pulmonary function tests provides information about the contribution of all respiratory muscles, the lungs and airways. Imaging potentially enables the study of different respiratory muscles, including the diaphragm, separately. In this review, we provide an overview of imaging techniques used to study respiratory muscles in neuromuscular disease. We identified 26 studies which included a total of 573 patients with neuromuscular disease. Imaging of respiratory muscles was divided into static and dynamic techniques. Static techniques comprise chest radiography, B-mode (brightness mode) ultrasound, CT and MRI, and are used to assess the position and thickness of the diaphragm and the other respiratory muscles. Dynamic techniques include fluoroscopy, M-mode (motion mode) ultrasound and MRI, used to assess diaphragm motion in one or more directions. We discuss how these imaging techniques relate with spirometric values and whether these can be used to study the contribution of the different respiratory muscles in patients with neuromuscular disease.</p
