Correlation Between Respiratory Accessory Muscles and Diaphragm Pillars MRI and Pulmonary Function Test in Late-Onset Pompe Disease Patients

Objectives: Pompe disease is a rare genetic disease produced by mutations in the GAA gene leading to progressive skeletal and respiratory muscle weakness. T1-weighted magnetic resonance imaging is useful to identify fatty replacement in skeletal muscles of late-onset Pompe disease (LOPD) patients. Previous studies have shown that replacement by fat correlates with worse results of muscle function tests. Our aim was to investigate if fat replacement of muscles involved in the ventilation process correlated with results of the spirometry and predicted respiratory muscle impairment in LOPD patients over time.Materials and Methods: We studied a cohort of 36 LOPD patients followed up annually in our center for a period of 4 years. We quantified muscle fat replacement using Mercuri score of the thoracic paraspinal and abdominal muscles and the pillars of the diaphragm. We correlated the combined Mercuri scores of these areas with spirometry results and the need of respiratory support.Results: We found a statistically significant correlation (Spearman test, p < 0.05; coefficient of correlation > 0.6) between forced vital capacity seated and lying and fat fraction score of all muscle groups studied. The group of patients who needed respiratory support had higher fat fraction scores than patients not requiring ventilatory support. Higher fat replacement in these areas correlated with worse progression in spirometry values over time.Conclusions: Fat replacement of paraspinal, abdominal, and trunk muscles correlates with results of spirometry and is able to predict worsening in respiratory muscle function tests that could lead to an emerging ventilatory dysfunction. Therefore, the identification of fat replacement in these muscle groups should lead to a closer monitorization of patients. Radiologic evaluation of diaphragm pillars in T1-weighted imaging axial sequences could also be helpful to predict respiratory insufficiency.

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Magnetization Transfer Ratio in Lower Limbs of Late Onset Pompe Patients Correlates With Intramuscular Fat Fraction and Muscle Function Tests

Frontiers in Neurology ◽

10.3389/fneur.2021.634766 ◽

2021 ◽

Vol 12 ◽

Author(s):

Claudia Nuñez-Peralta ◽

Paula Montesinos ◽

Alicia Alonso-Jiménez ◽

Jorge Alonso-Pérez ◽

David Reyes-Leiva ◽

...

Keyword(s):

Pompe Disease ◽

Muscle Function ◽

Late Onset ◽

Magnetization Transfer ◽

Intramuscular Fat ◽

Fatty Tissue ◽

Healthy Controls ◽

Function Tests ◽

Fat Fraction ◽

Spearman Test

Objectives: Magnetization transfer (MT) imaging exploits the interaction between bulk water protons and protons contained in macromolecules to induce signal changes through a special radiofrequency pulse. MT detects muscle damage in patients with neuromuscular conditions, such as limb-girdle muscular dystrophies or Charcot-Marie-Tooth disease, which are characterized by progressive fiber loss and replacement by fatty tissue. In Pompe disease, in which there is, in addition, an accumulation of glycogen inside the muscle fibers, MT has not been tested yet. Our aim is to estimate MT ratio (MTR) in the skeletal muscle of these patients and correlate it with intramuscular fat fraction (FF) and results of muscle function tests.Methods: We obtained two-point axial Dixon and Dixon-MT sequences of the right thigh on a 1.5 Teslas MRI scanner in 60 individuals, including 29 late onset Pompe disease patients, 2 patients with McArdle disease, and 29 age and sex matched healthy controls. FF and MTR were estimated. Muscle function using several muscle function tests, including quantification of muscle strength, timed test quality of life scales, conventional spirometry obtaining forced vital capacity while sitting and in the supine position, were assessed in all patients.Results: MTR was significantly lower in Pompe patients compared with controls (45.5 ± 8.5 vs. 51.7 ± 2.3, Student T-test, p < 0.05). There was a negative correlation between the MTR and FF muscles studied (correlation coefficient: −0.65, Spearman test: p < 0.05). MTR correlated with most of the muscle function test results. We analyzed if there was any difference in MTR values between Pompe patients and healthy controls in those muscles that did not have an increase in fat, a measure that could be related to the presence of glycogen in skeletal muscles, but we did not identify significant differences except in the adductor magnus muscle (48.4 ± 3.6 in Pompe vs. 51 ± 1.3 in healthy controls, Student T-test = 0.023).Conclusions: MTR is a sensitive tool to identify muscle loss in patients with Pompe disease and shows a good correlation with muscle function tests. Therefore, the MT technique can be useful in monitoring muscle degeneration in Pompe disease in clinical trials or natural history studies.

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Anaesthetic Management of Two Patients with Pompe Disease for Caesarean Section

Case Reports in Anesthesiology ◽

10.1155/2014/650310 ◽

2014 ◽

Vol 2014 ◽

pp. 1-3 ◽

Cited By ~ 1

Author(s):

I. J. J. Dons-Sinke ◽

M. Dirckx ◽

G. P. Scoones

Keyword(s):

Case Report ◽

Caesarean Section ◽

Enzyme Replacement Therapy ◽

Replacement Therapy ◽

Pompe Disease ◽

Muscle Function ◽

Respiratory Muscle ◽

Late Onset ◽

Anaesthetic Management ◽

Enzyme Replacement

The introduction of enzyme replacement therapy and the resultant stabilisation or improvement in mobility and respiratory muscle function afforded to patients with late-onset Pompe may lead to an increased number of Pompe patients prepared to accept the challenges of parenthood. In this case report, we describe our anaesthetic management of two patients with Pompe disease for a caesarean section.

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Distal muscle weakness is a common and early feature in long-term enzyme-treated classic infantile Pompe patients

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-020-01482-w ◽

2020 ◽

Vol 15 (1) ◽

Cited By ~ 1

Author(s):

J. J. A. van den Dorpel ◽

E. Poelman ◽

L. Harlaar ◽

H. A. van Kooten ◽

L. J. van der Giessen ◽

...

Keyword(s):

Muscle Weakness ◽

Pompe Disease ◽

Muscle Function ◽

Late Onset ◽

Walking Ability ◽

Proximal Muscle ◽

Muscle Involvement ◽

Enzyme Replacement ◽

Distal Muscle ◽

Over Time

Abstract Background Enzyme replacement therapy (ERT; alglucosidase alfa) has improved the prospects for patients with classic infantile Pompe disease considerably. However, over time we noticed that many of these children exhibit distal muscle weakness at an early age, which is in contrast to the primarily proximal and axial muscle weakness in patients with late-onset Pompe disease. This was reason to study the prevalence and severity of distal muscle weakness, and the sequence of muscle involvement over time in patients that had learned to walk under ERT. Methods In this prospective, single-center cohort study, we studied 16 classic infantile patients. We used video recordings that were made during regular standardized assessments to investigate distal muscle function (active dorsiflexion of the feet during walking; ability to use a pincer grasp/actively extend the fingers) and proximal muscle function (standing up from a supine position; raising the arms above the head). Results Median age at start of ERT was 3.2 months (0.1–5.8 months), median age at study end was 5.6 years (2.9–18.2 years). Six patients (6/16, 38%) initially had no evident signs of distal muscle weakness and developed a gait with active dorsiflexion of the feet. The other 10 patients never exhibited active dorsiflexion of the feet during walking. At study-end two patients showed no loss of distal muscle function. A subset of five patients (5/16, 31%) developed also weakness of the hands, particularly of the extensors of the 3rd and 4th digit. Conclusions We found that the majority (14/16, 88%) of patients who had learned to walk exhibited distal muscle weakness of the lower extremities, while a subset (5/16, 31%) also developed weakness of the hands. The distal muscle weakness was often more serious than, and preceded the development of, the proximal muscle weakness.

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Corrigendum: Magnetization Transfer Ratio in Lower Limbs of Late Onset Pompe Patients Correlates With Intramuscular Fat Fraction and Muscle Function Tests

Frontiers in Neurology ◽

10.3389/fneur.2021.727020 ◽

2021 ◽

Vol 12 ◽

Author(s):

Claudia Nuñez-Peralta ◽

Paula Montesinos ◽

Alicia Alonso-Jiménez ◽

Jorge Alonso-Pérez ◽

David Reyes-Leiva ◽

...

Keyword(s):

Muscle Function ◽

Late Onset ◽

Magnetization Transfer ◽

Intramuscular Fat ◽

Lower Limbs ◽

Magnetization Transfer Ratio ◽

Transfer Ratio ◽

Function Tests ◽

Fat Fraction

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Different Approaches to Analyze Muscle Fat Replacement With Dixon MRI in Pompe Disease

Frontiers in Neurology ◽

10.3389/fneur.2021.675781 ◽

2021 ◽

Vol 12 ◽

Author(s):

Alicia Alonso-Jiménez ◽

Claudia Nuñez-Peralta ◽

Paula Montesinos ◽

Jorge Alonso-Pérez ◽

Carme García ◽

...

Keyword(s):

Pompe Disease ◽

Muscle Function ◽

Quantitative Mri ◽

Suitable Alternative ◽

Reliable Technique ◽

Methods Of Analysis ◽

Function Tests ◽

Short Period ◽

Daunting Task ◽

Fat Fraction

Quantitative MRI is an increasingly used method to monitor disease progression in muscular disorders due to its ability to measure changes in muscle fat content (reported as fat fraction) over a short period. Being able to objectively measure such changes is crucial for the development of new treatments in clinical trials. However, the analysis of the images involved continues to be a daunting task because of the time needed. Whether a more specific analysis selecting individual muscles or a global one analyzing the whole thigh or compartments could be a suitable alternative has only been marginally studied. In our study we compare three methods of analysis of 2-point-dixon images in a cohort of 34 patients with late onset Pompe disease followed over a period of one year. We measured fat fraction on MRIs obtained at baseline and at year 1, and we calculated the increment of fat fraction. We correlated the results obtained with the results of muscle function tests to investigate whether the three methods of analysis were equivalent or not. We observed significant differences between the three methods in the estimation of the fat fraction at both baseline and year 1, but no difference was found in the increment in fat fraction between baseline and year 1. When we correlated the fat fraction obtained with each method and the muscle function tests, we found a significant correlation with most tests in all three methods, although in most comparisons the highest correlation coefficient was found with the analysis of individual muscles. We conclude that the fastest strategy of analysis assessing compartments or the whole thigh could be reliable for certain cohorts of patients where the variable to study is the fat increment. In other sorts of studies, an individual muscle approach seems the most reliable technique.

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Practical Recommendations for Diagnosis and Management of Respiratory Muscle Weakness in Late-Onset Pompe Disease

International Journal of Molecular Sciences ◽

10.3390/ijms17101735 ◽

2016 ◽

Vol 17 (10) ◽

pp. 1735 ◽

Cited By ~ 22

Author(s):

Matthias Boentert ◽

Hélène Prigent ◽

Katalin Várdi ◽

Harrison Jones ◽

Uwe Mellies ◽

...

Keyword(s):

Muscle Weakness ◽

Pompe Disease ◽

Respiratory Muscle ◽

Late Onset ◽

Respiratory Muscle Weakness ◽

Diagnosis And Management ◽

Practical Recommendations

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Respiratory muscle function in the critically ill

10.1093/med/9780199600830.003.0077 ◽

2016 ◽

Author(s):

Theodoros Vassilakopoulos ◽

Charis Roussos

Keyword(s):

Muscle Function ◽

Respiratory Muscle ◽

Magnetic Stimulation ◽

Abdominal Muscles ◽

Energy Demands ◽

Inspiratory Muscles ◽

Respiratory Muscle Function ◽

Generating Capacity ◽

Over Time ◽

Stimulation Of

The inspiratory muscles are the diaphragm, external intercostals and parasternal internal intercostal muscles. The internal intercostals and abdominal muscles are expiratory. The ability of a subject to take one breath depends on the balance between the load faced by the inspiratory muscles and their neuromuscular competence. The ability of a subject to sustain the respiratory load over time (endurance) depends on the balance between energy supplied to the inspiratory muscles and their energy demands. Hyperinflation puts the diaphragm at a great mechanical disadvantage, decreasing its force-generating capacity. In response to acute increases in load the inspiratory muscles become fatigued and inflammed. In response to reduction in load by the use of mechanical ventilation they develop atrophy and dysfunction. Global respiratory muscle function can be tested using maximum static inspiratory and expiratory mouth pressures, and sniff pressure. Diaphragm function can be tested by measuring the transdiaphragmatic and twitch pressures developed upon electrical or magnetic stimulation of the phrenic nerve.

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Dynamic respiratory muscle function in late-onset Pompe disease

Scientific Reports ◽

10.1038/s41598-019-54314-8 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Barbara K. Smith ◽

Shannon Allen ◽

Samantha Mays ◽

A. Daniel Martin ◽

Barry J. Byrne

Keyword(s):

Pompe Disease ◽

Respiratory Muscle ◽

Late Onset ◽

Pulmonary Function Tests ◽

Load Compensation ◽

Single Breath ◽

Muscle Adaptations ◽

Endurance Testing ◽

Chest Wall Kinematics ◽

Breathing Endurance

AbstractMaximal inspiratory pressure (PIMAX) reflects inspiratory weakness in late-onset Pompe disease (LOPD). However, static pressure tests may not reveal specific respiratory muscle adaptations to disruptions in breathing. We hypothesized that dynamic respiratory muscle functional tests reflect distinct ventilatory compensations in LOPD. We evaluated LOPD (n = 7) and healthy controls (CON, n = 7) during pulmonary function tests, inspiratory endurance testing, dynamic kinematic MRI of the thorax, and ventilatory adjustments to single-breath inspiratory loads (inspiratory load compensation, ILC). We observed significantly lower static and dynamic respiratory function in LOPD. PIMAX, spirometry, endurance time, and maximal diaphragm descent were significantly correlated. During single-breath inspiratory loads, inspiratory time and airflow acceleration increased to preserve volume, and in LOPD, the response magnitudes correlated to maximal chest wall kinematics. The results indicate that changes in diaphragmatic motor function and strength among LOPD subjects could be detected through dynamic respiratory testing. We concluded that neuromuscular function significantly influenced breathing endurance, timing and loading compensations.

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