Chest MRI May Help Monitor Pompe Progression, Treatment Efficacy

A study showed a significant change in the diaphragm's curvature in patients

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

Share this article:

Share article via email
Pompe disease symptoms | Pompe Disease News | MRI illustration

The function of the diaphragm, a major muscle in breathing, is significantly reduced over a year in adults with Pompe disease relative to healthy people, a small study showed.

These deficits, detected through a chest MRI test, were not accompanied by significant changes in lung function tests. In addition, patients with mild diaphragm dysfunction at the study’s start and those on enzyme replacement therapy (ERT) for up to three years did not show a significant worsening in diaphragm function over time.

The findings suggest MRI-assessed diaphragm function — particularly its curvature — may serve as an early biomarker of disease progression and may be used to monitor the effectiveness of treatment in this patient population, the researchers said.

The study, “MRI changes in diaphragmatic motion and curvature in Pompe disease over time,” was published in European Radiology.

Recommended Reading
ERT interruptions | Pompe Disease News | illustration of damaged lungs

Severe Impairments Seen in Diaphragm Motion, Study Shows

Pompe disease is a genetic disease marked by progressive muscle weakness that often impairs breathing. This is mainly caused by weakness in the diaphragm, the dome-shaped muscle that allows the chest to move with each breath.

ERT, the mainstay treatment for Pompe, delivers acid alpha-glucosidase, the missing enzyme in the disease, to patients.

While data suggest ERT can slow lung function decline, some patients may still show progressive respiratory muscle weakness despite starting ERT or “may have an initial positive effect followed by a secondary decline,” the researchers wrote.

Lung function tests can assess respiratory muscle strength, but not the function of individual muscles. MRI allows such analysis. Previous MRI-based studies showed that the motion of the diaphragm is reduced in Pompe patients and that changes could be detected before lung function dropped below normal.

During inspiration, the curvature of the diaphragm is normally reduced, but in Pompe patients, its shape was found to become more curved, indicating impaired muscle contraction.

Changes in diaphragm function over time

Researchers in the Netherlands set out to evaluate, for the first time, MRI-assessed changes in diaphragm function over time in people with Pompe.

The study included 30 adults (16 women and 14 men) with Pompe and 10 healthy adults (five women and five men), used as controls. Patients’ median age was 43 (range, 17–70) while that of controls was 37 (range, 26–63). There were no significant group differences in terms of sex, age, height, or weight.

Patients had been living with the disease for a median of 12 years (range, 0–38 years). None of them used a wheelchair, but one used nocturnal mechanical ventilation. Also, 15 patients (50%) were on ERT for more than three years, and eight (26%) for up to three years; the remaining seven were not on the therapy.

All the participants underwent lung function tests and chest MRI at the study’s start and one year later. In the MRI test, participants were asked to hold their breath for a few seconds both at maximum inspiration and at the end of expiration.

Diaphragmatic motion and curvature were calculated using a machine learning algorithm. Machine learning is a form of artificial intelligence that uses algorithms to analyze data, learn from its analyses, and then make a prediction about something.

Results showed that, at the study’s start, lung function and nearly all MRI outcomes, including overall lung volume and diaphragmatic motion, were significantly lower in people with Pompe than in controls.

Diaphragmatic curvature was similar between groups, which may be explained by the large variability in disease severity across patients, which included six with “no or only very mild symptoms of muscle weakness,” the research team wrote.

After one year, changes in lung function outcomes, overall lung volume, and diaphragmatic motion were not significantly different between the two groups. However, patients showed a significant increase in the curvature of the diaphragm after a year compared with controls.

“This corresponds to a more insufficient diaphragmatic contraction and may indicate progressive diaphragmatic dysfunction,” the researchers wrote.

A significant increase in diaphragmatic curvature over time was observed in untreated Pompe patients, in those on ERT for more than three years, and in patients with moderate to severe diaphragmatic weakness at the study’s start, subgroup analyses showed.

In contrast, the curvature of the diaphragm remained stable in healthy controls, Pompe patients on ERT for three years or less, and in patients with no to mild diaphragmatic weakness at initial MRI.

Recommended Reading
brain blood flow | Pompe Disease News | LOPD | illustration of conference room

Brain Blood Flow Changes May Be Complication of LOPD

A clear reduction in diaphragm curvature over time, indicating improved function, was detected in three patients. Two had no or minor diaphragm weakness at the study start and an ERT duration of up to three years, while the other had signs of moderate to severe weakness in the diaphragm.

The effect of treatment

These findings highlight that an MRI is able “to detect small changes in diaphragmatic curvature over 1-year time in Pompe patients,” the researchers wrote, adding that the changes “may serve as an outcome measure to evaluate the effect of treatment on diaphragmatic function.”

“MRI potentially can be used to identify Pompe patients with still normal standard pulmonary function tests and only minor diaphragmatic abnormalities who might benefit from an early start of ERT,” they added.

The fact that diaphragmatic curvature appeared to remain stable in Pompe patients treated with ERT for up to three years suggests “a positive effect on diaphragmatic function in the first years after starting ERT,” the research team wrote, adding that despite the subgroups being small and the findings being indicative only, “they parallel previous studies on the effects of ERT on [lung function tests] that showed that the main effects of ERT could be achieved during the first years after start of treatment.”

The data also suggested that “once severe diaphragmatic weakness has occurred, improvement of diaphragmatic muscle function seems unlikely,” the researchers wrote, noting larger studies are needed to further validate these MRI outcome measures before they can be used in clinical trials and future research should also assess whether these measures may be useful in children with classic and non-classic Pompe disease.