Quantitative whole‐body magnetic resonance imaging in children with Pompe disease: Clinical tools to evaluate severity of muscle disease

Abstract

ObjectiveSince the introduction of enzyme replacement therapy (ERT) with alglucosidase alfa, there has been increased survival in patients with Pompe disease. It is essential to characterize and quantify the burden of disease in these patients. Here, we report a measure of muscle fat infiltration in children with infantile and pediatric late‐onset Pompe disease (IPD and LOPD, respectively) to better understand the extent of muscle involvement.MethodsEleven pediatric patients with Pompe disease (five IPD, six LOPD), ages 7‐17 years, received whole‐body magnetic resonance imaging (WBMRI), muscle strength testing using the modified Medical Research Council (mMRC) scale, functional assessment using gait, stairs, gowers, chair (GSGC), and urine glucose tetrasaccharide (Glc4) testing. The intramuscular fat seen on WBMRI was quantified using proton density fat fraction (PDFF) and correlated to appropriate muscle strength and functional tests, and urine Glc4.ResultsPatients with IPD, although younger, had higher mean PDFF values than LOPD patients (11.61% vs 8.52%). Significant correlation existed between PDFF and the GSGC assessment (r = .9273, P = .0003). Moderate correlation existed between PDFF and mMRC (r = −.667, P = .0831), and PDFF and urine Glc4 (r = .6121, P = .0667). Anterior tibialis was in the top quartile of muscle involvement for patients with LOPD.ConclusionIn the past, physical therapy assessments alone have been used to track disease progression. Here, we show the clinical utility of WBMRI in quantifying muscle involvement in children with Pompe disease, especially regarding the novel involvement of anterior tibialis in children with LOPD, to better assess baseline muscle burden and mapping disease progression in children treated with ERT.

Muscle ultrasound in patients with late-onset Pompe disease identified by newborn screening

“…However, the methodology used on the upper third of the quadriceps complex included analysis of the rectus femoris in all patients. Our study's muscle pattern was generally similar to MRI findings in previous work in children with LOPD ages 7–17 [ 12 ]. Notably, involvement of the quadriceps was a key finding in both studies.…”

“…Magnetic resonance imaging (MRI) has been used in both IOPD and LOPD, revealing an association between worsening physical function and fatty infiltration compared to healthy controls [ 11 ]. MRI identifies a distinct pattern of muscle involvement in Pompe disease but is expensive and requires considerable time and sedation to evaluate babies and children [ 12 ]. Muscle ultrasound (US) can be used for the same purpose via measurement of muscle brightness, known as echointensity (EI).…”

Non-invasive optoacoustic imaging of glycogen-storage and muscle degeneration in Late-onset Pompe disease

“…48,49 The quanti cation of intramuscular fat or fat fraction (FF) has been shown to provide a solid correlation with muscle function and clinical outcomes in adults. 17,18,[50][51][52] Less consistent results, as demonstrated in our study, facilitated the development of more sophisticated muscle MRI sequences, including diffusion tensor imaging or glycogen spectroscopy. 53 However, MRI may have several disadvantages, such as high costs, limited availability, lack of (inter-center) protocol standardization, and long examination time coupled with strict positioning of the patient.…”

Quantitative muscle ultrasound and electrical impedance myography in late onset Pompe disease: A pilot study of reliability, longitudinal change and correlation with function

“…Clinical outcome measures like the 6-min walk test are affected by numerous factors, including patient participation and disease severity, as some patients may lose the ability to ambulate [ 4 ]. Whole body MRI of muscle is an alternative outcome measure but is costly and not easy to perform in patients with advanced respiratory muscle weakness [ 8 , 11 ]. Non-invasive, inexpensive, point-of-care methods for assessing muscle health are needed for clinical trials and health tracking, particularly methods that can be performed at home.…”