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A team of researchers examined the evolution of the use of skeletal magnetic resonance imaging (MRI) in tracking muscular deterioration in Pompe disease. Their findings were published in Muscle & Nerve. We will take a closer look at some of their findings in this article. 

Muscle MRI has been used to track muscle loss in a multitude of neuromuscular disorders, including Pompe disease. Conventional MRI works by allowing physicians to keep track of the structural change in muscles through the detection of fat replacement and increased water content. When muscle wasting occurs, skeletal muscle is replaced by fat tissue.

Hence, conventional MRI can track slowly progressive muscle wasting, such as which occurs in Pompe disease; however, it is not useful for short-term disease tracking as the differences may not be noticeable over a short period of time. 


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The difficulty in conventional MRI, of course, is that muscle water is not easily visualized due to the domination of fatty tissue because of the soft-tissue sensitivity of MRI. However, advances in MRI technology now allow for the specific quantification of fatty tissue present in muscles, which opens a new door of opportunity for tracking muscular progression. 

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More sophisticated software allows for quantitative tracking of fat in T1-weighted images. For example, chemical shift-encoded imaging is able to separate fat from water and create fat and water fraction maps based on differences in chemical shifts. 

“Increased water content can be detected in various situations, such as inflammation, muscle necrosis, or acute denervation, and it is generally considered a sign of acute and active damage,” the authors of the review explained.

Most studies involving muscle MRI and Pompe disease are directed at late-onset Pompe disease (LOPD). In these patients, physicians can observe greater fat replacement in the lower limbs than the upper limbs. In addition, proximal muscles are more commonly affected than distal muscles. 

In addition, muscle fat reveals a good deal about muscle function and strength. Studies have shown that fat replacement in muscle MRI corresponds with the progressive impairment of muscle function in patients with Pompe disease. Muscle MRI is even able to detect presymptomatic patients by virtue of mild fatty replacement of muscles.

Muscle MRI as a Diagnostic Tool

Muscle MRI is useful for diagnosing Pompe disease because it can be clearly differentiated from other neuromuscular disorders, such as the various forms of muscular dystrophies. In Pompe disease, the distal leg muscles are often spared; in muscular dystrophies, they are often affected.

Muscle MRI can also differentiate Pompe disease from sarcoglycanopathies: they differ from Pompe disease in that there is the heavy involvement of the scapular, biceps, and triceps brachii muscles; furthermore, there is a complete replacement of the gluteus maximus by fat early in sarcoglycanopathies.

Measuring Outcomes With Muscle MRI 

In light of this, some have suggested muscle MRI as an outcome measure in LOPD patients. A study took the baseline MRI of LOPD study participants before the initiation of ERT. After therapy was initiated, researchers were able to observe an increase in muscle size in some areas, as well as an increase in motor function in functional studies. Researchers theorized that the increase in muscle size was due to the ability of non-damaged muscle fibers to metabolize glycogen and recover some normality in muscle function and structure. 

In another study, LOPD patients were followed up for a period of three years. A total of 36 patients were recruited in this study; among them, 23 were symptomatic patients who received ERT at baseline. MRI imaging of these patients revealed a significant mean increase of 5.8% in the mean thigh fat fraction after 3 years of follow-up. Within the same period, muscle strength tests demonstrated a significant decrease in both hand-held dynamometry and manual muscle testing. 

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These results are significant because they suggest that ERT does not stop the replacement of muscle with fat, since the percentage of fat in muscles still rose even with treatment. Researchers observed that muscle volume initially improved within 6 months of treatment, then declined when treatment was continued for longer periods.

“There are several unsolved issues that need further analysis,” opined the authors of the review, chief of all insufficient data of symptomatic patients not treated with ERT. Needless to say, creating such a cohort in a study would be unethical, meaning parts of muscle MRI studies in patients with Pompe disease will always remain unsatisfactory. 

The Work Ahead 

What the various studies cited in this article have demonstrated is that muscle MRI is a useful tool to track disease progression in LOPD patients, especially when new MRI technology is better able to visualize muscle fat and water percentage. Certainly, larger-scale and longer-term studies need to be carried out for us to get a better bird’s eye view of the extent of the usefulness of muscle MRI in tracking Pompe disease. 

In fact, some make the argument that it is more crucial for us to strengthen our most basic understanding of how Pompe disease causes muscular dysfunction in the first place.

“With many of the disease symptoms attributed to smooth muscle dysfunction, more research is needed to elucidate how glycogen accumulation disrupts normal smooth muscle function,” McCall et al suggest. “Not only is a greater understanding of the cellular mechanism and pathophysiology of the disease in smooth muscle crucial, but evaluation of the effectiveness of ERT and novel therapies in these tissues should be taken into consideration.”

References

Díaz-Manera J, Walter G, Straub V. Skeletal muscle magnetic resonance imaging in Pompe diseaseMuscle Nerve. Published online November 6, 2020. doi:10.1002/mus.27099

McCall AL, Salemi J, Bhanap P, Strickland LM, Elmallah MK. The impact of Pompe disease on smooth muscle: a reviewJ Smooth Muscle Res. Published online February 20, 2019. doi:10.1540/jsmr.54.100