Muscle MRI Correlates With FSHD Children’s Functional Measures

Muscle weakness in FSHD mainly affects the face, shoulders, and upper arms

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by Andrea Lobo |

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A technician stands over a person as they are about to enter a MRI scanner.

Whole-body muscle MRI correlates with functional measures in children with facioscapulohumeral muscular dystrophy (FSHD) and might help evaluate disease severity, according to a study.

“This study demonstrates that MR muscle imaging is a potential biomarker of disease staging in pediatric FSHD,” the researchers wrote in “Correlation between whole body muscle MRI and functional measures in pediatric patients with facioscapulohumeral muscular dystrophy,” which was published in Neuromuscular Disorders.

A feature of FSHD is muscle weakness that mainly affects the face, shoulders, and upper arms. In type 1, the most common, the disease is caused by a shortening of the D4Z4 region of chromosome 4, causing the DUX4 gene to become activated. This leads to the DUX4 protein being produced, which is thought to be toxic to muscle cells.

People normally show their first symptoms toward the end of their 20s. However, some develop symptoms in childhood. Pediatric FSHD is usually associated with more severe symptoms and a more rapid progression.

Symptoms vary regarding the muscles affected, age at presentation, and rate of progression, meaning the traditional measures for monitoring progression might not be sensitive in the disease’s initial phases.

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Scoring muscle to fat, wasting, edema with MRI

In this study conducted in Australia, a MRI was used in children with FSHD to define the muscles involved and at what severity, and to compare the MRI evaluation with valid disease-specific functional measures.

The researchers evaluated 11 patients with FSHD type 1, ages 7–15 (55% boys), who were recruited to a clinical trial (NCT02948244) at a single site in Melbourne. Whole-body MRI and functional outcomes were evaluated at the beginning of the study, and at four later times.

After a preselection based on published data for adult patients. the team focused on muscles in the upper and lower limbs, and in the abdomen.

Replacement of muscle by fat tissue, muscle wasting, and muscle edema (swelling) were scored for each muscle, and added up to give each patient three cumulative scores.

The amount of fat in muscle and severity of muscle wasting correlated strongly with clinical measures of muscle strength, evaluated by existing disease severity scales — the FSHD-Clinical Score (CS) and FSHD-Clinical Severity Scale (CSS) — and the FSHD-Composite Outcome Measure, an emerging functional scale.

The score for muscle edema correlated poorly with the clinical functional measures, however.

“Muscle edema,” the researchers wrote, “may predict and precede clinical muscle weakness, suggesting the clinical scores may actually be lagging behind the MRI changes,” the researchers wrote.

Weak correlation in muscle strength, manual testing

Other functional measures, such as myometry, which quantifies muscle strength using a held-hand device, and manual muscle testing (MMT), were moderately or weakly correlated with the MRI findings.

Although MMT has been used as the primary outcome in clinical trials in adults with FSDH, “the variability seen in this study suggests that its utility may be limited in pediatric patients,” the scientists wrote. As for myometry, the team noted that, while it may be a more sensitive measure than MMT, the scores in this small group were too spread out to be generalizable.

The Motor Function Measure for Neuromuscular Diseases (MFM-32) had a limited correlation with MRI, in that the less severely affected children scored maximum points and couldn’t be further tested. Also, high scores by some participants that suggested mild disease did not correlate with MRI muscle changes.

“MFM-32 lacks the sensitivity to detect small change in those with minimally to mildly affected muscles on the MRI,” the researchers said.

The Six Minute Walk Test correlated with MRI scores less strongly than other functional measures. This is probably because children with FSHD maintain the ability to walk, even when the upper limbs are severely affected, the scientists said.

The study suggests scores of muscle to fat replacement or wasting using whole-body MRI “correlate strongly with disease-specific functional measures and may be a useful measure of disease severity in pediatric FSHD,” the researchers wrote, noting that each participant having only one MRI scan made it impossible to assess its responsiveness to change over time, making that a limitation of the study.