scholarly journals Clinical Evaluation of Duchenne Muscular Dystrophy Severity Using Ultrasound Small-Window Entropy Imaging

Entropy ◽  
2020 ◽  
Vol 22 (7) ◽  
pp. 715 ◽  
Author(s):  
Dong Yan ◽  
Qiang Li ◽  
Chia-Wei Lin ◽  
Jeng-Yi Shieh ◽  
Wen-Chin Weng ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Ultrasound Imaging ◽  
Characteristic Curve ◽  
Image Data ◽  
Control Group ◽  
Information Uncertainty ◽  
Small Window ◽  
Stage 1

Information entropy of ultrasound imaging recently receives much attention in the diagnosis of Duchenne muscular dystrophy (DMD). DMD is the most common muscular disorder; patients lose their ambulation in the later stages of the disease. Ultrasound imaging enables routine examinations and the follow-up of patients with DMD. Conventionally, the probability distribution of the received backscattered echo signals can be described using statistical models for ultrasound parametric imaging to characterize muscle tissue. Small-window entropy imaging is an efficient nonmodel-based approach to analyzing the backscattered statistical properties. This study explored the feasibility of using ultrasound small-window entropy imaging in evaluating the severity of DMD. A total of 85 participants were recruited. For each patient, ultrasound scans of the gastrocnemius were performed to acquire raw image data for B-mode and small-window entropy imaging, which were compared with clinical diagnoses of DMD by using the receiver operating characteristic curve. The results indicated that entropy imaging can visualize changes in the information uncertainty of ultrasound backscattered signals. The median with interquartile range (IQR) of the entropy value was 4.99 (IQR: 4.98–5.00) for the control group, 5.04 (IQR: 5.01–5.05) for stage 1 patients, 5.07 (IQR: 5.06–5.07) for stage 2 patients, and 5.07 (IQR: 5.06–5.07) for stage 3 patients. The diagnostic accuracies were 89.41%, 87.06%, and 72.94% for ≥stage 1, ≥stage 2, and ≥stage 3, respectively. Comparisons with previous studies revealed that the small-window entropy imaging technique exhibits higher diagnostic performance than conventional methods. Its further development is recommended for potential use in clinical evaluations and the follow-up of patients with DMD.

scholarly journals Open-Label Evaluation of Eteplirsen in Patients with Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping: PROMOVI Trial

2021 ◽  
pp. 1-13
Author(s):  
Craig M. McDonald ◽  
Perry B. Shieh ◽  
Hoda Z. Abdel-Hamid ◽  
Anne M. Connolly ◽  
Emma Ciafaloni ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Natural History ◽  
Adverse Events ◽  
Exon Skipping ◽  
Control Group ◽  
Phase 2 ◽  
Open Label ◽  
M Phase ◽  
Positive Treatment

Background Eteplirsen received accelerated FDA approval for treatment of Duchenne muscular dystrophy (DMD) with mutations amenable to exon 51 skipping, based on demonstrated dystrophin production. Objective To report results from PROMOVI, a phase 3, multicenter, open-label study evaluating efficacy and safety of eteplirsen in a larger cohort. Methods Ambulatory patients aged 7–16 years, with confirmed mutations amenable to exon 51 skipping, received eteplirsen 30 mg/kg/week intravenously for 96 weeks. An untreated cohort with DMD not amenable to exon 51 skipping was also enrolled. Results 78/79 eteplirsen-treated patients completed 96 weeks of treatment. 15/30 untreated patients completed the study; this cohort was considered an inappropriate control group because of genotype-driven differences in clinical trajectory. At Week 96, eteplirsen-treated patients showed increased exon skipping (18.7-fold) and dystrophin protein (7-fold) versus baseline. Post-hoc comparisons with patients from eteplirsen phase 2 studies (4658-201/202) and mutation-matched external natural history controls confirmed previous results, suggesting clinically notable attenuation of decline on the 6-minute walk test over 96 weeks (PROMOVI: –68.9 m; phase 2 studies: –67.3 m; external controls: –133.8 m) and significant attenuation of percent predicted forced vital capacity annual decline (PROMOVI: –3.3%, phase 2 studies: –2.2%, external controls: –6.0%; p <  0.001). Adverse events were generally mild to moderate and unrelated to eteplirsen. Most frequent treatment-related adverse events were headache and vomiting; none led to treatment discontinuation. Conclusions This large, multicenter study contributes to the growing body of evidence for eteplirsen, confirming a positive treatment effect, favorable safety profile, and slowing of disease progression versus natural history.

Long-term follow-up of dysphagia in adult patients with Duchenne muscular dystrophy

2018 ◽  
Vol 22 (5) ◽  
pp. 786-790 ◽  
Author(s):  
Yuka Yamada ◽  
Michiyuki Kawakami ◽  
Ayako Wada ◽  
Shogo Fukui ◽  
Koshiro Haruyama ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Adult Patients ◽  
Long Term Follow Up

scholarly journals Noninvasive evaluation of respiratory muscles in pre-clinical model of Duchenne Muscular Dystrophy

2016 ◽  
Vol 36 (4) ◽  
pp. 290-296
Author(s):  
Daniela M. Oliveira ◽  
Stefano C. Hagen ◽  
Amilton C. Santos ◽  
Maria A. Miglino ◽  
Antônio C. Assis Neto
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Respiratory Muscles ◽  
Experimental Models ◽  
Noninvasive Evaluation ◽  
Control Group ◽  
Clinical Model ◽  
Intercostal Muscles ◽  
Invasive Method ◽  
Clinical Conditions

Abstract Since respiratory insufficiency is the main cause of death in patients affected by Duchenne Muscular Dystrophy (DMD), the present study aims at establishing a new non-invasive method to evaluate the clinical parameters of respiratory conditions of experimental models affected by DMD. With this purpose in mind, we evaluated the cardiorespiratory clinical conditions, the changes in the intercostal muscles, the diaphragmatic mobility, and the respiratory cycles in Golden Retriever Muscular Dystrophy (GRMD) employing ultrasonography (US). A control group consisting of dogs of the same race, but not affected by muscular dystrophy, were used in this study. The results showed that inspiration, expiration and plateau movements (diaphragm mobility) were lower in the affected group. Plateau phase in the affected group was practically non-existent and showed that the diaphragm remained in constant motion. Respiratory rate reached 15.5 per minute for affected group and 26.93 per minute for the control group. Expiration and inspiration movements of intercostal muscles reached 8.99mm and 8.79mm, respectively, for control group and 7.42mm and 7.40mm, respectively, for affected group. Methodology used in the present analysis proved to be viable for the follow-up and evaluation of the respiratory model in GRMD and may be adapted to other muscular dystrophy experimental models.

scholarly journals Autonomic modulation at rest and in response to postural change in adolescents with Duchenne muscular dystrophy: a cross-sectional study

2021 ◽  
Vol 79 (9) ◽  
pp. 766-773
Author(s):  
Mariana Viana Rodrigues ◽  
Mileide Cristina Stoco-Oliveira ◽  
Talita Dias da Silva ◽  
Celso Ferreira ◽  
Heloisa Balotari Valente ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Oxygen Saturation ◽  
Cross Sectional Study ◽  
Control Group ◽  
Autonomic Modulation ◽  
Postural Change ◽  
Cross Sectional

ABSTRACT Background: Analysis of autonomic modulation after postural change may inform the prognosis and guide treatment in different populations. However, this has been insufficiently explored among adolescents with Duchenne muscular dystrophy (DMD). Objective: To investigate autonomic modulation at rest and in response to an active sitting test (AST) among adolescents with DMD. Methods: Fifty-nine adolescents were included in the study and divided into two groups: 1) DMD group: adolescents diagnosed with DMD; 2) control group (CG): healthy adolescents. Participants’ weight and height were assessed. Lower limb function, motor limitations and functional abilities of the participants in the DMD group were classified using the Vignos scale, Egen classification and motor function measurement, respectively. The following variables were assessed before, during and after AST: systolic blood pressure (SBP), diastolic blood pressure (DBP), respiratory rate (f), oxygen saturation and heart rate (HR). To analyze the autonomic modulation, the HR was recorded beat-by-beat. Heart rate variability (HRV) indices were calculated in the time and frequency domains. Results: Differences in relation to groups were observed for all HRV indices, except LF/HF, oxygen saturation, HR and f (p < 0.05). Differences in relation to time and the interaction effect between group and time were observed for RMSSD, SD1, SD2, SD1/SD2, LFms2 and LFnu, HFun, SBP and DBP (p < 0.05). Differences in relation to time were also observed for the indice SDNN, FC and f (p < 0.05). Conclusions: Performing the AST promoted reduced autonomic modulation and increased SBP, DBP and HR in adolescents with DMD.

scholarly journals Longitudinal Motor Functional Outcomes and Magnetic Resonance Imaging Patterns of Muscle Involvement in Upper Limbs in Duchenne Muscular Dystrophy

Medicina ◽  
2021 ◽  
Vol 57 (11) ◽  
pp. 1267
Author(s):  
Claudia Brogna ◽  
Lara Cristiano ◽  
Tommaso Verdolotti ◽  
Giulia Norcia ◽  
Luana Ficociello ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Duchenne Muscular Dystrophy ◽  
Magnetic Resonance ◽  
Muscular Dystrophy ◽  
Resonance Imaging ◽  
Muscle Mri ◽  
Functional Changes ◽  
One Year ◽  
Age Range

Background and Objectives: The aim of this study was to evaluate longitudinal changes using both upper limb muscle Magnetic Resonance Imaging (MRI) at shoulder, arm and forearm levels and Performance of upper limb (PUL) in ambulant and non-ambulant Duchenne Muscular Dystrophy (DMD) patients. We also wished to define whether baseline muscle MRI could help to predict functional changes after one year. Materials and Methods: Twenty-seven patients had both baseline and 12month muscle MRI and PUL assessments one year later. Results: Ten were ambulant (age range 5–16 years), and 17 non ambulant (age range 10–30 years). Increased abnormalities equal or more than 1.5 point on muscle MRI at follow up were found on all domains: at shoulder level 12/27 patients (44%), at arm level 4/27 (15%) and at forearm level 6/27 (22%). Lower follow up PUL score were found in 8/27 patients (30%) at shoulder level, in 9/27 patients (33%) at mid-level whereas no functional changes were found at distal level. There was no constant association between baseline MRI scores and follow up PUL scores at arm and forearm levels but at shoulder level patients with moderate impairment on the baseline MRI scores between 16 and 34 had the highest risk of decreased function on PUL over a year. Conclusions: Our results confirmed that the integrated use of functional scales and imaging can help to monitor functional and MRI changes over time.

scholarly journals Mast cells in the pathophysiology of Duchenne muscular dystrophy in Golden Retriever dogs

2020 ◽  
Vol 40 (10) ◽  
pp. 791-797
Author(s):  
Isabela M. Martins ◽  
Lygia M.M. Malvestio ◽  
Jair R. Engracia-Filho ◽  
Gustavo S. Claudiano ◽  
Flávio R. Moraes ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Mast Cells ◽  
Muscular Dystrophy ◽  
Fibrous Tissue ◽  
Control Group ◽  
Golden Retriever ◽  
Collagenous Tissue ◽  
Muscle Types ◽  
Muscle Groups

ABSTRACT: The Golden Retriever muscular dystrophy (GRMD) is one of the best models of Duchenne muscular dystrophy (DMD), with similar genotypic and phenotypic manifestations. Progressive proliferation of connective tissue in the endomysium of the muscle fibers occurs in parallel with the clinical course of the disease in GRMD animals. Previous studies suggest a relationship between mast cells and the deposition of fibrous tissue due to the release of mediators that recruit fibroblasts. The aim of this study was to evaluate the presence of mast cells and their relationship with muscle injury and fibrosis in GRMD dogs of different ages. Samples of muscle groups from six GRMD and four control dogs, aged 2 to 8 months, were collected and analyzed. The samples were processed and stained with HE, toluidine blue, and Azan trichrome. Our results showed that there was a significant increase in infiltration of mast cells in all muscle groups of GRMD dogs compared to the control group. The average number of mast cells, as well as the deposition of fibrous tissue, decreased with age in GRMD dogs. In the control group, all muscle types showed a significant increase in the amount of collagenous tissue. This suggests increased mast cell degranulation occurred in younger GRMD dogs, resulting in increased interstitial space and fibrous tissue in muscle, which then gradually decreased over time as the dogs aged. However, further studies are needed to clarify the role of mast cells in the pathogenesis of fibrosis.

Progression of muscular co-activation and gait variability in children with Duchenne muscular dystrophy: A 2-year follow-up study

2020 ◽  
Vol 78 ◽  
pp. 105101
Author(s):  
Martina Rinaldi ◽  
Maurizio Petrarca ◽  
Alberto Romano ◽  
Gessica Vasco ◽  
Carmen D'Anna ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Gait Variability ◽  
Follow Up Study ◽  
Co Activation

scholarly journals Comparison of Serum Pharmacodynamic Biomarkers in Prednisone-Versus Deflazacort-Treated Duchenne Muscular Dystrophy Boys

2020 ◽  
Vol 10 (4) ◽  
pp. 164
Author(s):  
Shefa Tawalbeh ◽  
Alison Samsel ◽  
Heather Gordish-Dressman ◽  
Yetrib Hathout ◽  
CINRG-DNHS Investigators ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Natural History Study ◽  
Motor Abilities ◽  
Igf I ◽  
Comparative Safety ◽  
Pharmacodynamic Biomarkers ◽  
Larger Sample ◽  
Insight Into

Prednisone (Pred) and Deflazacort (Dfz) are commonly used glucocorticoids (GCs) for Duchenne muscular dystrophy (DMD) treatment and management. While GCs are known to delay the loss of ambulation and motor abilities, chronic use can result in onerous side effects, e.g., weight gain, growth stunting, loss of bone density, etc. Here, we use the CINRG Duchenne natural history study to gain insight into comparative safety of Pred versus Dfz treatment through GC-responsive pharmacodynamic (PD) biomarkers. Longitudinal trajectories of SOMAscan® protein data obtained on serum of DMD boys aged 4 to 10 (Pred: n = 7; Dfz: n = 8) were analyzed after accounting for age and time on treatment. Out of the pre-specified biomarkers, seventeen candidate proteins were differentially altered between the two drugs (p < 0.05). These include IGFBP-2 and AGER associated with diabetes complications, and MMP-3 associated with extracellular remodeling. As a follow-up, IGFBP-2, MMP-3, and IGF-I were quantified with an ELISA using a larger sample size of DMD biosamples (Dfz: n = 17, Pred: n = 12; up to 76 sera samples) over a longer treatment duration. MMP-3 and IGFBP-2 validated the SOMAscan® signal, however, IGF-I did not. This study identified GC-responsive biomarkers, some associated with safety, that highlight differential PD response between Dfz and Pred.

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