Autonomic Modulation in Duchenne Muscular Dystrophy During a Computer Task: A Prospective Transversal Controlled Trial Assessment by Non-linear Techniques

Introduction: Due to functional and autonomic difficulties faced by individuals with Duchenne Muscular Dystrophy (DMD), the use of assistive technology is critical to provide or facilitate functional abilities. The key objective was to investigate acute cardiac autonomic responses, by application of Heart Rate Variability (HRV), during computer tasks in subjects with DMD via techniques based on non-linear dynamics.Method: HRV was attained via a Polar RS800CX. Then, was evaluated by Chaotic Global Techniques (CGT). Forty-five male subjects were included in the DMD group and age-matched with 45 in the healthy Typical Development (TD) control group. They were assessed for 20 min at rest sitting, and then 5 min whilst performing the maze task on a computer.Results: Both TD and DMD subjects exhibited a significantly reduced HRV measured by chaotic global combinations when undertaking the computer maze paradigm tests. DMD subjects presented decreased HRV during rest and computer task than TD subjects.Conclusion: While there is an impaired HRV in subjects with DMD, there remains an adaptation of the ANS during the computer tasks. The identification of autonomic impairment is critical, considering that the computer tasks in the DMD community may elevate their level of social inclusion, participation and independence.

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Treatment of Duchenne muscular dystrophy with cyclosporin A – A randomized, double-blind, placebo controlled trial

Neuropediatrics ◽

10.1055/s-0029-1215757 ◽

2008 ◽

Vol 39 (05) ◽

Author(s):

J Kirschner ◽

J Schessl ◽

G Ihorst ◽

R Korinthenberg

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Cyclosporin A ◽

Controlled Trial ◽

Double Blind ◽

Double Blind Placebo

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

Journal of Neuromuscular Diseases ◽

10.3233/jnd-210643 ◽

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.

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Faculty Opinions recommendation of Randomised controlled trial evaluating the use of Zoledronic acid in Duchenne Muscular Dystrophy.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.740069858.793585943 ◽

2021 ◽

Author(s):

Madhusmita Misra

Keyword(s):

Duchenne Muscular Dystrophy ◽

Zoledronic Acid ◽

Randomised Controlled Trial ◽

Muscular Dystrophy ◽

Controlled Trial ◽

Randomised Controlled

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

Pesquisa Veterinária Brasileira ◽

10.1590/s0100-736x2016000400007 ◽

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.

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

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x-anp-2020-0458 ◽

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.

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

Pesquisa Veterinária Brasileira ◽

10.1590/1678-5150-pvb-6340 ◽

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.

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