MRI as outcome measure in facioscapulohumeral muscular dystrophy: 1-year follow-up of 45 patients

Abstract

There is no effective treatment available for facioscapulohumeral muscular dystrophy type 1 (FSHD1), but emerging therapies are under way that call for a better understanding of natural history in this condition. In this prospective, longitudinal study, we used quantitative MRI to assess yearly disease progression in patients with FSHD1. Ambulatory patients with confirmed diagnosis of FSHD1 (25/20 men/women, age 20-75 years, FSHD score: 0-12) were tested with 359-560-day interval between tests. Using the MRI Dixon technique, muscle fat replacement was evaluated in paraspinal, thigh, and calf muscles. Changes were compared with those in FSHD score, muscle strength (hand-held dynamometry), 6-minute-walk-distance, 14-step-stair-test, and 5-time-sit-to-stand-test. Composite absolute fat fraction of all assessed muscles increased by 0.036 (CI 0.026-0.046, P < 0.001), with increases in all measured muscle groups. The clinical severity FSHD score worsened (10%, P < 0.05), muscle strength decreased over the hip (8%), neck (8%), and back (17%) (P < 0.05), but other strength measures, 6-minute-walk-distance, 5-times-sit-to-stand-test, and 14-step-stair-test were unchanged. Changes in muscle strength, FSHD score, and fat fraction did not correlate. This first study to systemically monitor quantitative fat replacement longitudinally in FSHD1 shows that MRI provides an objective measure of disease progression, often before changes can be appreciated in strength and functional tests. The study indicates that quantitative MRI can be a helpful end-point in follow-up and therapeutic trials of patients with FSHD1.

Disease progression and outcome measures in spinobulbar muscular atrophy

“…Dixon MRI has previously been shown to be able to detect disease progression in muscular dystrophies when other measures could not, 11,12 which is in line with our findings in SBMA. Dixon MRI has previously been shown to be able to detect disease progression in muscular dystrophies when other measures could not, 11,12 which is in line with our findings in SBMA.…”

“…11,12 The annual increase in mean muscle fat content was 1.4% (range = 0.8-1.9%) in SBMA, which is comparable with other slowly progressive neuromuscular diseases. Similar variations and decreases over time have been described in other neuromuscular diseases.…”

Advancements in magnetic resonance imaging‐based biomarkers for muscular dystrophy

“…Multiple studies in Duchenne muscular dystrophy (DMD) have shown that Dixon imaging sequences can capture increasing fat replacement over time, and additional studies have demonstrated strong correlation between muscle fat fractions and quantitative muscle strength . Studies in facioscapulohumeral muscular dystrophy (FSHD) have also shown that fat fractions derived from Dixon imaging correspond to disease‐specific scales and clinical outcome measures . Dixon imaging has similarly been used to examine skeletal muscles in the Becker and limb‐girdle muscular dystrophy populations …”

“…The primary advantage that MRI offers to researchers in muscular dystrophy is the ability to detect very small increments of true pathologic change in skeletal muscle . This capability alone would represent a significant improvement over the existing outcome measures that are being used in clinical trials, which are primarily strength and timed function tests.…”

Current body composition measurement techniques

“…Andersen et al reported that, for patients with facioscapulohumeral muscular dystrophy type 1 (FSHD), a condition that is characterized by asymmetrical and progressive wasting of leg muscles, leg MRI was able to detect disease progression before the clinical test of functional outcomes (such as FSHD score, muscle strength by hand-held dynamometry, walking, or step-stair tests) [32]. A single slice cross-sectional area at mid-femur has also been proposed to be used in clinical practice for a fast and noninvasive diagnosis of sarcopenia in older adults [33].…”