Дискретно-континуальные системы: подходы, модели, программно-модельные комплексы

<div><p>Background</p><p>Diaphragm weakness is the main reason for respiratory dysfunction in patients with Pompe disease, a progressive metabolic myopathy affecting respiratory and limb-girdle muscles. Since respiratory failure is the major cause of death among adult patients, early identification of respiratory muscle involvement is necessary to initiate treatment in time and possibly prevent irreversible damage. In this paper we investigate the suitability of dynamic MR imaging in combination with state-of-the-art image analysis methods to assess respiratory muscle weakness.</p><p>Methods</p><p>The proposed methodology relies on image registration and lung surface extraction to quantify lung kinematics during breathing. This allows for the extraction of geometry and motion features of the lung that characterize the independent contribution of the diaphragm and the thoracic muscles to the respiratory cycle.</p><p>Results</p><p>Results in 16 3D+t MRI scans (10 Pompe patients and 6 controls) of a slow expiratory maneuver show that kinematic analysis from dynamic 3D images reveals important additional information about diaphragm mechanics and respiratory muscle involvement when compared to conventional pulmonary function tests. Pompe patients with severely reduced pulmonary function showed severe diaphragm weakness presented by minimal motion of the diaphragm. In patients with moderately reduced pulmonary function, cranial displacement of posterior diaphragm parts was reduced and the diaphragm dome was oriented more horizontally at full inspiration compared to healthy controls.</p><p>Conclusion</p><p>Dynamic 3D MRI provides data for analyzing the contribution of both diaphragm and thoracic muscles independently. The proposed image analysis method has the potential to detect less severe diaphragm weakness and could thus be used to determine the optimal start of treatment in adult patients with Pompe disease in prospect of increased treatment response.</p></div

Prospective exploratory muscle biopsy, imaging, and functional assessment in patients with late-onset Pompe disease treated with alglucosidase alfa: The EMBASSY Study

Background Late-onset Pompe disease is characterized by progressive skeletal myopathy followed by respiratory muscle weakness, typically leading to loss of ambulation and respiratory failure. In this population, enzyme replacement therapy (ERT) with alglucosidase alfa has been shown to stabilize respiratory function and improve mobility and muscle strength. Muscle pathology and glycogen clearance from skeletal muscle in treatment-naïve adults after ERT have not been extensively examined. Methods This exploratory, open-label, multicenter study evaluated glycogen clearance in muscle tissue samples collected pre- and post- alglucosidase alfa treatment in treatment-naïve adults with late-onset Pompe disease. The primary endpoint was the quantitative reduction in percent tissue area occupied by glycogen in muscle biopsies from baseline to 6 months. Secondary endpoints included qualitative histologic assessment of tissue glycogen distribution, secondary pathology changes, assessment of magnetic resonance images (MRIs) for intact muscle and fatty replacement, and functional assessments. Results Sixteen patients completed the study. After 6 months of ERT, the percent tissue area occupied by glycogen in quadriceps and deltoid muscles decreased in 10 and 8 patients, respectively. No changes were detected on MRI from baseline to 6 months. A majority of patients showed improvements on functional assessments after 6 months of treatment. All treatment-related adverse events were mild or moderate. Conclusions This exploratory study provides novel insights into the histopathologic effects of ERT in late-onset Pompe disease patients. Ultrastructural examination of muscle biopsies demonstrated reduced lysosomal glycogen after ERT. Findings are consistent with stabilization of disease by ERT in treatment-naïve patients with late-onset Pompe disease

Increased aortic stiffness and blood pressure in non-classic Pompe disease

Vascular abnormalities and glycogen accumulation in vascular smooth muscle fibres have been described in Pompe disease. Using carotid-femoral pulse wave velocity (cfPWV), the gold standard methodology for determining aortic stiffness, we studied whether aortic stiffness is increased in patients with Pompe disease. Eighty-four adult Pompe patients and 179 age- and gender-matched volunteers participated in this cross-sectional case-controlled study. Intima media thickness and the distensibility of the right common carotid artery were measured using a Duplex scanner. Aortic augmentation index, central pulse pressure, aortic reflexion time and cfPWV were assessed using the SphygmoCor® system. CfPWV was higher in patients than in volunteers (8.8 versus 7.4 m/s, p < 0.001). This difference was still present after adjustment for age, gender, mean arterial blood pressure (MAP), heart rate and diabetes mellitus (p = 0.001), and was shown by subgroup analysis to apply to the 40-59 years age group (p = 0.004) and 60+ years age group (p = 0.01), but not to younger age groups (p = 0.99). Except for a shorter aortic reflexion time (p = 0.02), indirect indicators of arterial stiffness did not differ between patients and volunteers. Relative to volunteers (20 %), more Pompe patients had a history of hypertension (36 %, p = 0.005), and the MAP was higher than in volunteers (100 versus 92 mmHg, p < 0.001). This study shows that patients with non-classic Pompe disease have increased aortic stiffness and blood pressure. Whether this is due to glycogen accumulation requires further investigation. To reduce the potential risk of cardiovascular diseases, we recommend that blood pressure and other common cardiovascular risk factors are monitored regularly

Safety and efficacy of exercise training in adults with Pompe disease: evalution of endurance, muscle strength and core stability before and after a 12 week training program

BACKGROUND: Pompe disease is a proximal myopathy. We investigated whether exercise training is a safe and useful adjuvant therapy for adult Pompe patients, receiving enzyme replacement therapy. METHODS: Training comprised 36 sessions of standardized aerobic, resistance and core stability exercises over 12 weeks. Before and after, the primary outcome measures safety, endurance (aerobic exercise capacity and distance walked on the 6 min walk test) and muscle strength, and secondary outcome measures core stability, muscle function and body composition, were evaluated. RESULTS: Of 25 patients enrolled, 23 successfully completed the training. Improvements in endurance were shown by increases in maximum workload capacity (110 W before to 122 W after training, [95 % CI of the difference 6 · 0 to 19 · 7]), maximal oxygen uptake capacity (69 · 4 % and 75 · 9 % of normal, [2 · 5 to 10 · 4]), and maximum walking distance (6 min walk test: 492 meters and 508, [−4 · 4 to 27 · 7] ). There were increases in muscle strength of the hip flexors (156 · 4 N to 180 · 7 N [1 · 6 to 13 · 6) and shoulder abductors (143 · 1 N to 150 · 7 N [13 · 2 to 35 · 2]). As an important finding in secondary outcome measures the number of patients who were able to perform the core stability exercises rose, as did the core stability balancing time (p < 0.05, for all four exercises). Functional tests showed small reductions in the time needed to climb four steps (2 · 4 sec to 2 · 1, [− 0 · 54 to −0 · 04 ]) and rise to standing position (5 · 8 sec to 4 · 8, [−2 · 0 to 0 · 0]), while time to run, the quick motor function test results and body composition remained unchanged. CONCLUSIONS: Our study shows that a combination of aerobic, strength and core stability exercises is feasible, safe and beneficial to adults with Pompe disease

Overview of the lung surface partitioning procedure.

<p>The diagram shows the individual steps to subdivide the surface mesh of a binary lung segmentation into six parts. In the two main parts the costal surface is extracted and the residual surface is divided into diaphragmatic and medial surface.</p

Cranial excursion of the right hemidiaphragm: anterior vs. posterior.

<p>The light and dark boxplots for each subject represent the cranial excursion of all points in the anterior and posterior part of the right diaphragm dome, respectively. Significant differences between anterior and posterior excursion are marked with triangles (down-pointing triangle: larger anterior excursion, up-pointing triangle: larger posterior excursion) and circles indicate no significant difference.</p

Chest wall and diaphragm contribution to overall lung volume change.

<p>The bar plot shows the amount of volume displaced by the costal surface (upper bars) and diaphragm surface (lower bars) for all subjects. Patients (<i>P01</i>—<i>P10</i>) and controls (<i>C01</i>—<i>C06</i>) are sorted within their group in descending order with respect to supine FVC (% of predicted).</p