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1.
J Rehabil Med ; 52(9): jrm00102, 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32870317

RESUMO

OBJECTIVE: To propose alternative learning strategies for glossopharyngeal breathing in patients with Duchenne muscular dystrophy (DMD) and healthy men. DESIGN: A feasibility study with small case series. SUBJECTS: Five boys with DMD and 7 male physical therapists as healthy controls who had not learned glossopharyngeal breathing. METHODS: Participants were instructed in a glossopharyngeal breathing protocol, including induction methods comprising sucking motions and phonation with inhalation. The protocol consisted of 1-6 sessions (10-15 min each; total 60 min). Criteria for glossopharyngeal breathing mastery were vital capacity with glossopharyngeal insufflation (VCGI)/VC ratio > 1.10 for the DMD group and > 1.05 for the Healthy group. Feasibility outcomes were time required for mastering glossopharyngeal breathing, self-reported outcomes, adverse events and drop-outs. RESULTS: All participants learned glossopharyngeal breathing within the allocated 60 min. Mean VCGI/VC ratio was 1.31 for the DMD group and 1.09 for the Healthy group. No adverse events or drop-outs were encountered during the protocol. In most cases, self-reported outcomes showed that motivation increased and difficulty decreased. CONCLUSION: Induction methods for sucking motions and phonation with inhalation for glossopharyngeal breathing learning are feasible. This paper proposes alternative strategies for glossopharyngeal breathing learning in boys with DMD and their instructors.


Assuntos
Distrofia Muscular de Duchenne/complicações , Respiração/genética , Adulto , Estudos de Viabilidade , Humanos , Masculino , Adulto Jovem
2.
Pediatrics ; 146(3)2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32826339

RESUMO

Disorders of central and peripheral nervous system should be considered in floppy infants with ventilator dependence. Workup for neuromuscular disorders should be undertaken in infants with hypotonia, weakness, contractures, feeding difficulties, or failed attempts at extubation. We present the case of a preterm infant with hypotonia and ventilator dependence where despite a positive result, further investigations were undertaken because of lack of clinical correlation. The infant had a rare combination of 2 neuromuscular conditions: X-linked myotubular myopathy and Duchenne muscular dystrophy. One was the reason for immediate clinical manifestation and the other influenced the prognosis and decision-making in determining reorientation of care. This case demonstrates the value of interpretation of a positive result that did not explain the clinical picture and warranted consideration of further diagnosis. This case also emphasizes the importance of discussions with family about the prognosis of 2 conditions that influenced decision making.


Assuntos
Recém-Nascido Prematuro , Distrofia Muscular de Duchenne/complicações , Distrofia Muscular de Duchenne/diagnóstico , Miopatias Congênitas Estruturais/complicações , Miopatias Congênitas Estruturais/diagnóstico , Evolução Fatal , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro/fisiologia , Masculino , Distrofia Muscular de Duchenne/genética , Miopatias Congênitas Estruturais/genética
3.
Pharmacol Res ; 158: 104917, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32485610

RESUMO

At the moment, little treatment options are available for Duchenne muscular dystrophy (DMD). The absence of the dystrophin protein leads to a complex cascade of pathogenic events in myofibres, including chronic inflammation and oxidative stress as well as altered metabolism. The attention towards dietary supplements in DMD is rapidly increasing, with the aim to counteract pathology-related alteration in nutrient intake, the consequences of catabolic distress or to enhance the immunological response of patients as nowadays for the COVID-19 pandemic emergency. By definition, supplements do not exert therapeutic actions, although a great confusion may arise in daily life by the improper distinction between supplements and therapeutic compounds. For most supplements, little research has been done and little evidence is available concerning their effects in DMD as well as their preventing actions against infections. Often these are not prescribed by clinicians and patients/caregivers do not discuss the use with their clinical team. Then, little is known about the real extent of supplement use in DMD patients. It is mistakenly assumed that, since compounds are of natural origin, if a supplement is not effective, it will also do no harm. However, supplements can have serious side effects and also have harmful interactions, in terms of reducing efficacy or leading to toxicity, with other therapies. It is therefore pivotal to shed light on this unclear scenario for the sake of patients. This review discusses the supplements mostly used by DMD patients, focusing on their potential toxicity, due to a variety of mechanisms including pharmacodynamic or pharmacokinetic interactions and contaminations, as well as on reports of adverse events. This overview underlines the need for caution in uncontrolled use of dietary supplements in fragile populations such as DMD patients. A culture of appropriate use has to be implemented between clinicians and patients' groups.


Assuntos
Betacoronavirus , Infecções por Coronavirus/dietoterapia , Suplementos Nutricionais/efeitos adversos , Interações Medicamentosas , Distrofia Muscular de Duchenne/dietoterapia , Pneumonia Viral/dietoterapia , Padrão de Cuidado , Infecções por Coronavirus/complicações , Humanos , Distrofia Muscular de Duchenne/complicações , Pandemias , Pneumonia Viral/complicações
4.
Pediatr Cardiol ; 41(6): 1173-1179, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32476037

RESUMO

Cardiomyopathy is the leading cause of death in Duchenne muscular dystrophy (DMD). Elevated troponin levels are observed in DMD and may vary with disease progression. We studied troponin levels in DMD related to cardiac fibrosis and native T1 measures. This is a prospective, cross-sectional, observational study of 30 DMD subjects measuring native T1 levels and late gadolinium enhancement (LGE) on cardiac MR imaging (CMR) correlated with temporally associated serum troponin I levels. Non-parametric analyses including Spearman correlations and Kruskal-Wallis test were performed between groups. p values resulting from the pair-wise comparisons were adjusted for multiple comparisons using the Sidak method where appropriate. There were 15 DMD subjects with no LGE (age 12 ± 3 yo; EF% 60 ± 5) and troponin I level of 0.05 ± 0.08 ng/ml, of which three had an abnormal troponin level (over 0.04 ng/ml); 7 DMD subjects with mild LGE (age 17 ± 5 yo, EF% 52 ± 8) and troponin I level of 0.28 ± 0.36 ng/ml, of which five had an abnormal troponin level; and 8 DMD subjects with moderate-to-severe LGE (age 16 ± 6 yo; EF% 54 ± 8) and troponin I level of 0.11 ± 0.14 ng/ml, of which four had an abnormal troponin level. Troponin I levels in DMD subjects with mild LGE was significantly increased compared to subjects with no LGE (p = 0.02). There was a statistically significant positive correlation between troponin I levels and MOLLI septal native T1 values (r2 = 0.173, p = 0.02). Overall, MOLLI lateral native T1 levels were increased with moderate-severe LGE compared to mild and none (p < 0.01). Serum biomarker troponin I levels were increased in DMD subjects with mild LGE and correlated with MOLLI septal native T1 values. Troponin I levels may be a useful minimally invasive outcome marker to monitor myocardial disease progression in DMD cardiomyopathy.


Assuntos
Cardiomiopatias/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Distrofia Muscular de Duchenne/complicações , Troponina I/sangue , Adolescente , Biomarcadores/sangue , Cardiomiopatias/etiologia , Criança , Meios de Contraste/administração & dosagem , Estudos Transversais , Progressão da Doença , Feminino , Gadolínio/administração & dosagem , Humanos , Masculino , Estudos Prospectivos , Adulto Jovem
5.
Am J Physiol Heart Circ Physiol ; 318(6): H1436-H1440, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32383994

RESUMO

Cardiac arrhythmias significantly contribute to mortality in Duchenne muscular dystrophy (DMD), a degenerative muscle disease triggered by mutations in the gene encoding for the intracellular protein dystrophin. A major source for the arrhythmias in patients with DMD is impaired ventricular impulse conduction, which predisposes for ventricular asynchrony, decreased cardiac output, and the development of reentrant mechanisms. The reason for ventricular conduction impairments and the associated arrhythmias in the dystrophic heart has remained unidentified. In the present study, we explored the hypothesis that dystrophin-deficient cardiac Purkinje fibers have reduced Na+ currents (INa), which would represent a potential mechanism underlying slowed ventricular conduction in the dystrophic heart. Therefore, by using a Langendorff perfusion system, we isolated Purkinje fibers from the hearts of adult wild-type control and dystrophin-deficient mdx mice. Enhanced green fluorescent protein (eGFP) expression under control of the connexin 40 gene allowed us to discriminate Purkinje fibers from eGFP-negative ventricular working cardiomyocytes after cell isolation. Finally, we recorded INa from wild-type and dystrophic mdx Purkinje fibers for comparison by means of the whole cell patch clamp technique. We found substantially reduced INa densities in mdx compared with wild-type Purkinje fibers, suggesting that dystrophin deficiency diminishes INa. Because Na+ channels in the Purkinje fiber membrane represent key determinants of ventricular conduction velocity, we propose that reduced INa in Purkinje fibers at least partly explains impaired ventricular conduction and the associated arrhythmias in the dystrophic heart.NEW & NOTEWORTHY Dystrophic cardiac Purkinje fibers have abnormally reduced Na+ current densities. This explains impaired ventricular conduction in the dystrophic heart.


Assuntos
Arritmias Cardíacas/metabolismo , Doença do Sistema de Condução Cardíaco/metabolismo , Distrofia Muscular de Duchenne/metabolismo , Ramos Subendocárdicos/metabolismo , Canais de Sódio/metabolismo , Potenciais de Ação/fisiologia , Animais , Arritmias Cardíacas/complicações , Arritmias Cardíacas/fisiopatologia , Doença do Sistema de Condução Cardíaco/complicações , Doença do Sistema de Condução Cardíaco/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos mdx , Distrofia Muscular de Duchenne/complicações , Distrofia Muscular de Duchenne/fisiopatologia , Sódio/metabolismo
6.
PLoS One ; 15(5): e0229753, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32407333

RESUMO

Serum activities of alanine and aspartate aminotransferases (ALT and AST) are used as gold standard biomarkers for the diagnosis of hepatocellular injury. Since ALT and AST lack liver specificity, the diagnosis of the onset of hepatocellular injury in patients with underlying muscle impairments is severely limited. Thus, we evaluated the potential of glutamate dehydrogenase (GLDH) as a liver specific alternative biomarker of hepatocellular injury. In our study, serum GLDH in subjects with Duchene muscular dystrophy (DMD) was equivalent to serum GLDH in age matched healthy subjects, while serum ALT was increased 20-fold in DMD subjects. Furthermore, serum GLDH in 131 subjects with variety of muscle impairments was similar to serum GLDH of healthy subjects while serum ALT corelated with serum creatine kinase, a widely accepted biomarker of muscle impairment. In addition, significant elevations of ALT, AST, and CK were observed in a case of a patient with rhabdomyolysis, while serum GLDH stayed within the normal range until the onset of hypoxia-induced liver injury. In a mouse model of DMD (DMDmdx), serum GLDH but not serum ALT clearly correlated with the degree of acetaminophen-induced liver injury. Taken together, our data support the utility of serum GLDH as a liver-specific biomarker of liver injury that has a potential to improve diagnosis of hepatocellular injury in patients with underlying muscle impairments. In drug development, GLDH may have utility as a biomarker of drug induced liver injury in clinical trials of new therapies to treat muscle diseases such as DMD.


Assuntos
Biomarcadores/sangue , Doença Hepática Induzida por Substâncias e Drogas/sangue , Glutamato Desidrogenase/sangue , Distrofia Muscular de Duchenne/sangue , Acetaminofen/efeitos adversos , Adolescente , Adulto , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Doença Hepática Induzida por Substâncias e Drogas/complicações , Doença Hepática Induzida por Substâncias e Drogas/patologia , Criança , Pré-Escolar , Creatina Quinase/sangue , Modelos Animais de Doenças , Diagnóstico Precoce , Feminino , Humanos , Hipóxia/sangue , Hipóxia/complicações , Fígado/lesões , Fígado/patologia , Masculino , Camundongos , Distrofia Muscular de Duchenne/complicações , Distrofia Muscular de Duchenne/tratamento farmacológico , Distrofia Muscular de Duchenne/patologia , Rabdomiólise/sangue , Rabdomiólise/complicações , Rabdomiólise/patologia
7.
PLoS One ; 15(5): e0233527, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32469921

RESUMO

The prevalence of urinary incontinence in Duchenne and Becker muscular dystrophy (D/BMD) is reported to be between 15-29%, this however includes ages across the lifespan, and with no description of impact on daily life. The present study, aimed to determine the prevalence of urinary incontinence in men with D/BMD, and to identify which aspects of daily life were impacted by urinary incontinence. Twenty-seven adult males, 11 with BMD and 16 with DMD, aged 20-57 years, volunteered to participate in this study. Six questionnaires were completed to provide an overview of participant mobility, urinary incontinence and distress caused by urinary incontinence. These included: The Barthel index of disability, International Consultation on Incontinence Questionnaire-Urinary Incontinence Form, Incontinence Impact Questionnaire Short Form, The Urogenital Distress Inventory, and the Brooke and Vignos scale. The prevalence of urinary incontinence within the present men with D/BMD was 37%, assessed as urine leakage of once a week or more. Those with urinary incontinence all reported only a "small amount" of urine leakage, with urinary incontinence frequency of once a week in 5/10 participants, two or three times a week in 2/10 participants, and once a day in 3/10 participants. Of those with urinary incontinence 8/10 experienced some impact on their daily life from urine leakage including travel (4/10), social aspects (5/10), and emotional aspects (8/10). All participants with urinary incontinence were bothered by some aspect, including urine leakage (9/10), and frequent urination (4/10). In conclusion, 37% of the present men with D/BMD experience urinary incontinence on a weekly or daily basis and negatively impacted aspects of life related to travel, social and emotional wellbeing. Urine leakage, and frequent urination should be considered a meaningful problem by care providers, and discussed openly with those with D/BMD.


Assuntos
Distrofia Muscular de Duchenne/complicações , Incontinência Urinária/epidemiologia , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Inquéritos e Questionários , Incontinência Urinária/etiologia , Adulto Jovem
8.
Muscle Nerve ; 62(1): 41-45, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32329920

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic has resulted in the reorganization of health-care settings affecting clinical care delivery to patients with Duchenne and Becker muscular dystrophy (DBMD) as well as other inherited muscular dystrophies. The magnitude of the impact of this public health emergency on the care of patients with DBMD is unclear as they are suspected of having an increased risk for severe manifestations of COVID-19. In this article, the authors discuss their consensus recommendations pertaining to care of these patients during the pandemic. We address issues surrounding corticosteroid and exon-skipping treatments, cardiac medications, hydroxychloroquine use, emergency/respiratory care, rehabilitation management, and the conduct of clinical trials. We highlight the importance of collaborative treatment decisions between the patient, family, and health-care provider, considering any geographic or institution-specific policies and precautions for COVID-19. We advocate for continuing multidisciplinary care for these patients using telehealth.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Gerenciamento Clínico , Distrofia Muscular de Duchenne/terapia , Pandemias , Pneumonia Viral/complicações , Infecções por Coronavirus/epidemiologia , Humanos , Distrofia Muscular de Duchenne/complicações , Pneumonia Viral/epidemiologia
9.
Pediatr Cardiol ; 41(5): 925-931, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32157397

RESUMO

Duchenne muscular dystrophy (DMD) is characterized by myocardial fibrosis and left ventricular (LV) dysfunction. Implantable cardioverter defibrillator (ICD) use has not been characterized in this population but is considered for symptomatic patients with severe LV dysfunction (SLVD) receiving guideline-directed medical therapy (GDMT). We evaluated ICD utilization and efficacy in patients with DMD. Retrospective cohort study of DMD patients from 17 centers across North America between January 2, 2005 and December 31, 2015. ICD use and its effect on survival were evaluated in patients with SLVD defined as ejection fraction (EF) < 35% and/ or shortening fraction (SF) < 16% on final echocardiogram. SLVD was present in 57/436 (13.1%) patients, of which 12 (21.1%) died during the study period. Of these 12, (mean EF 20.9 ± 6.2% and SF 13.7 ± 7.2%), 8 received GDMT, 5 received steroids, and none received an ICD. ICDs were placed in 9/57 (15.8%) patients with SLVD (mean EF 31.2 ± 8.5% and SF 10.3 ± 4.9%) at a mean age of 20.4 ± 6.3 years; 8/9 received GDMT, 7 received steroids, and all were alive at study end; mean ICD duration was 36.1 ± 26.2 months. Nine ICDs were implanted at six different institutions, associated with two appropriate shocks for ventricular tachycardia in two patients, no inappropriate shocks, and one lead fracture. ICD use may be associated with improved survival and minimal complications in DMD cardiomyopathy with SLVD. However, inconsistent GDMT utilization may be a significant confounder. Future studies should define optimal indications for ICD implantation in patients with DMD cardiomyopathy.


Assuntos
Desfibriladores Implantáveis , Distrofia Muscular de Duchenne/complicações , Disfunção Ventricular Esquerda/cirurgia , Adolescente , Adulto , Ecocardiografia , Feminino , Humanos , Masculino , Distrofia Muscular de Duchenne/terapia , Estudos Retrospectivos , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/mortalidade , Adulto Jovem
10.
Eur J Paediatr Neurol ; 26: 20-28, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32165079

RESUMO

OBJECTIVES: Sleep health in rare disease is often overlooked due to the complex nature of the disease. For males with Duchenne muscular dystrophy, sleep assessment is typically focused on pulmonary function and identification of sleep disordered breathing. Unfortunately for young boys with Duchenne muscular dystrophy, sleep assessment is often neglected, resulting in a dearth of knowledge on sleep health in this population. This study describes sleep quantity and quality in both younger (4-9 years) and older (10-17 years) males with Duchenne muscular dystrophy (n = 19) and compares these characteristics with sleep characteristics of unaffected peers (n = 17). METHODS: This study was a longitudinal, observational study. Sleep measures were collected using the parent-proxy Children's Sleep Habits Questionnaire-Abbreviated version and objective sleep measures from actigraphy (sleep efficiency, awakenings, and awakening duration) over 30 days for all participants. Means and standard deviations were examined, and effect sizes were computed to quantify the magnitude of difference between the Duchenne muscular dystrophy and unaffected groups. RESULTS: Overall, boys with Duchenne muscular dystrophy were found to experience worse sleep than their unaffected peers as measured by parent report and actigraphy. Effect sizes of both measures demonstrated moderate to large magnitudes of difference in many of the sleep variables. Parents of boys with Duchenne muscular dystrophy reported higher scores (indicating worse sleep) in all subsections and total score of the Children's Sleep Habits Questionnaire - Abbreviated version. Actigraphy data indicated that the Duchenne muscular dystrophy group had lower percent sleep efficiency, more night awakenings and longer duration of night awakenings than their unaffected peers. CONCLUSION: Our findings offer a novel look into sleep in young boys with Duchenne muscular dystrophy. Both parent-report and actigraphy data indicate poor sleep health in this population compared with age-matched unaffected peers. Actigraphy was found to align with parent-report of sleep in this population, supporting the use of these two different ways to measure sleep in Duchenne muscular dystrophy. Results from this study should encourage clinicians and researchers alike to further explore sleep and its impact on disease in young boys with Duchenne muscular dystrophy.


Assuntos
Distrofia Muscular de Duchenne/fisiopatologia , Sono/fisiologia , Adolescente , Criança , Pré-Escolar , Humanos , Estudos Longitudinais , Masculino , Distrofia Muscular de Duchenne/complicações , Inquéritos e Questionários
11.
Am J Phys Med Rehabil ; 99(9): 789-794, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32195737

RESUMO

OBJECTIVE: Prevalence and characteristics of fractures and factors related to loss of ambulation after lower limb fractures were investigated. DESIGN: Chart review included height, weight, dual-energy x-ray absorptiometry, corticosteroid use, vitamin D, fracture history, muscle strength, range of motion, and timed performance tests (10 meter walk/run, Gowers, and four steps). Patients were grouped by fracture location and ambulation loss after fracture. RESULTS: Two hundred eighty-seven patients with Duchenne muscular dystrophy were identified, 53 of these had experienced fracture. Eighty-one percent were older than 9 yrs at first fracture and 36.4% became nonambulatory after fracture. Dorsiflexion range of motion (fracture side, P = 0.021), quadriceps strength (right side, P = 0.025), and shoulder abduction strength (right, left, and fracture side; P = 0.028, P = 0.027, and P = 0.016) were significantly different within the groups. Patients who became nonambulatory after fracture initially had less dorsiflexion (right, left, fracture side; 2.25 vs. -7.29, P = 0.004; 2.67 vs. -12, P = 0.001; and 2.41 vs. -7.42, P = 0.002) and slower 10-meter walk/run times (7.43 secs vs. 14.7 secs, P = 0.005). CONCLUSIONS: Fracture represents a significant risk in patients with Duchenne muscular dystrophy; both slower walking speed and ankle contracture confer an increased risk of ambulation loss after fracture. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) Identify the main factors that are associated with ambulation loss after fracture in patients with Duchenne muscular dystrophy; (2) Identify the risk of fracture in the Duchenne muscular dystrophy population; and (3) Articulate the characteristics associated with fracture in patients with Duchenne muscular dystrophy. LEVEL: Advanced. ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.


Assuntos
Fraturas Ósseas/fisiopatologia , Extremidade Inferior/lesões , Limitação da Mobilidade , Distrofia Muscular de Duchenne/fisiopatologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Fraturas Ósseas/etiologia , Humanos , Extremidade Inferior/fisiopatologia , Masculino , Distrofia Muscular de Duchenne/complicações , Amplitude de Movimento Articular , Estudos Retrospectivos , Fatores de Risco , Caminhada/fisiologia , Adulto Jovem
12.
J Neuromuscul Dis ; 7(2): 101-107, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31903995

RESUMO

BACKGROUND: Duchenne muscular dystrophy (DMD) patients can have various issues that affect their quality of life, including eating and digestive conditions. OBJECTIVE: We sought to identify the relationship between respiratory function and various eating and digestion related symptoms in patients with advanced Duchenne muscular dystrophy (DMD). METHODS: Eating and digestive symptoms, including loss of appetite, nausea, vomiting, diarrhea, constipation, swallowing difficulty, mastication difficulty, early satiety, and aspiration, were evaluated among patients with advanced DMD who were nonambulatory and required noninvasive mechanical ventilatory support. In addition, various respiratory function parameters were measured, including forced vital capacity (FVC), maximal insufflation capacity (MIC), peak cough flow (PCF), assisted PCF (APCF), maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP). We then analyzed the relationship between gastrointestinal symptoms and respiratory function parameters. RESULTS: A total of 180 patients (age, 22.3±5.0 years) were included in the analysis. Loss of appetite and early satiety showed no correlation with any of the respiratory function parameters. Constipation was correlated with MEP; swallowing difficulty was correlated with MIC, APCF, MIP and MEP; and mastication difficulty was correlated with FVC, PCF, APCF, MIP, and MEP. Notably, age did not correlate with any gastrointestinal symptoms. CONCLUSIONS: Eating and digestive symptoms are more closely correlated with respiratory function than with age in patients with DMD. We think this correlation is mainly caused by the skeletal muscle strength, which is major determinant of both digestive and respiratory function.


Assuntos
Gastroenteropatias/fisiopatologia , Distrofia Muscular de Duchenne/fisiopatologia , Transtornos Respiratórios/fisiopatologia , Índice de Gravidade de Doença , Adolescente , Adulto , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/fisiopatologia , Gastroenteropatias/etiologia , Humanos , Masculino , Distrofia Muscular de Duchenne/complicações , Ventilação não Invasiva , Transtornos Respiratórios/etiologia , Testes de Função Respiratória , Estudos Retrospectivos , Adulto Jovem
14.
Eur J Paediatr Neurol ; 25: 120-126, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31964551

RESUMO

Neurocognitive deficits are frequently described in Duchenne muscular dystrophy (DMD), but it is unknown how these progress over time. Our aim was to longitudinally assess verbal span capacity and information processing speed in DMD and to explore a genotype-phenotype relation. Verbal span and processing speed scores were available of 28 males with DMD on two time-points, with a mean time interval of 28.34 months (SD = 16.09). The cohort contained of six patients missing only dystrophin isoform Dp427, sixteen missing Dp427 and Dp140, and six were undeterminable. A lower verbal span capacity was found at the first and second assessment, whereas processing speed was normal at both time-points. Post-hoc analyses suggested lower scores on verbal span and processing speed for patients missing Dp427 and Dp140. In DMD, a developmental stagnation in verbal span capacity, irrespective of normal processing speed, is detected through longitudinal follow-up. This appears more pronounced in patients missing Dp427 and Dp140.


Assuntos
Distrofia Muscular de Duchenne/complicações , Transtornos do Neurodesenvolvimento/genética , Comportamento Verbal , Criança , Cognição/fisiologia , Distrofina/genética , Seguimentos , Estudos de Associação Genética , Humanos , Estudos Longitudinais , Masculino , Distrofia Muscular de Duchenne/genética
15.
Neurology ; 94(13): e1386-e1394, 2020 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-31937624

RESUMO

OBJECTIVE: We studied the potential of quantitative MRI (qMRI) as a surrogate endpoint in Duchenne muscular dystrophy by assessing the additive predictive value of vastus lateralis (VL) fat fraction (FF) to age on loss of ambulation (LoA). METHODS: VL FFs were determined on longitudinal Dixon MRI scans from 2 natural history studies in Leiden University Medical Center (LUMC) and Cincinnati Children's Hospital Medical Center (CCHMC). CCHMC included ambulant patients, while LUMC included a mixed ambulant and nonambulant population. We fitted longitudinal VL FF values to a sigmoidal curve using a mixed model with random slope to predict individual trajectories. The additive value of VL FF over age to predict LoA was calculated from a Cox model, yielding a hazard ratio. RESULTS: Eighty-nine MRIs of 19 LUMC and 15 CCHMC patients were included. At similar age, 6-minute walking test distances were smaller and VL FFs were correspondingly higher in LUMC compared to CCHMC patients. Hazard ratio of a percent-point increase in VL FF for the time to LoA was 1.15 for LUMC (95% confidence interval [CI] 1.05-1.26; p = 0.003) and 0.96 for CCHMC (95% CI 0.84-1.10; p = 0.569). CONCLUSIONS: The hazard ratio of 1.15 corresponds to a 4.11-fold increase of the instantaneous risk of LoA in patients with a 10% higher VL FF at any age. Although results should be confirmed in a larger cohort with prospective determination of the clinical endpoint, this added predictive value of VL FF to age on LoA supports the use of qMRI FF as an endpoint or stratification tool in clinical trials.


Assuntos
Tecido Adiposo/patologia , Limitação da Mobilidade , Distrofia Muscular de Duchenne/complicações , Músculo Quadríceps/patologia , Tecido Adiposo/diagnóstico por imagem , Criança , Humanos , Imagem por Ressonância Magnética , Masculino , Distrofia Muscular de Duchenne/diagnóstico por imagem , Distrofia Muscular de Duchenne/patologia , Músculo Quadríceps/diagnóstico por imagem
16.
Muscle Nerve ; 61(2): 213-217, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31778229

RESUMO

BACKGROUND: Dysphagia is reported in patients with Duchenne or Becker muscular dystrophy. Our clinical experience suggests that, compared with Duchenne patients, impaired mastication and swallowing occur early in Becker patients relative to their skeletal muscle involvement. The aim of this study was to assess dysphagia in Duchenne and Becker patients in relation to ambulatory capacity. METHODS: In patients in the early ambulatory stage, clinical symptoms, quantitative muscle ultrasound of the orofacial muscles, and maximum bite force were assessed. The 6-Minute Walk Test (6MWT) was used to measure ambulatory capacity. RESULTS: Eleven Duchenne and 11 Becker patients were included. Although Becker patients had a greater 6MWT distance than Duchenne patients, the occurrence of mastication and swallowing difficulties was similar. The temporalis muscle was significantly thicker in Becker patients. CONCLUSIONS: Clinicians should be aware of dysphagia in both groups, even when ambulation is still well preserved.


Assuntos
Músculos Faciais/fisiopatologia , Músculos da Mastigação/fisiopatologia , Distrofia Muscular de Duchenne/fisiopatologia , Algoritmos , Força de Mordida , Criança , Transtornos de Deglutição/etiologia , Músculos Faciais/diagnóstico por imagem , Humanos , Masculino , Mastigação , Músculos da Mastigação/diagnóstico por imagem , Distrofia Muscular de Duchenne/complicações , Ultrassonografia , Teste de Caminhada , Caminhada
17.
Muscle Nerve ; 61(2): 192-197, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31725904

RESUMO

INTRODUCTION: With improved treatments, patients with Duchenne muscular dystrophy (DMD) can survive far beyond adolescence. However, advanced-stage DMD patients are at risk of developing renal dysfunction. In this study, long-term renal function outcomes and associated risk factors in advanced stage DMD were analyzed. METHODS: Fifty-one patients were classified into three different age groups (<20, 20-29, and ≥30 years of age), and cystatin C (CysC) levels were compared among groups. RESULTS: Median serum CysC levels were 0.74 mg/L, 0.63 mg/L, and 0.76 mg/L in the age groups of <20, 20-29, and ≥30 years, respectively (P = .003). Five of the nine patients in the ≥30 years age group showed elevated serum CysC and decreased cardiac function compared with the other four in the group (P = .014). DISCUSSION: Our results indicate an association between cardiac and renal dysfunction in patients with advanced-stage DMD.


Assuntos
Nefropatias/etiologia , Distrofia Muscular de Duchenne/complicações , Adolescente , Adulto , Envelhecimento , Criança , Pré-Escolar , Cistatina C/sangue , Progressão da Doença , Feminino , Cardiopatias/etiologia , Cardiopatias/fisiopatologia , Testes de Função Cardíaca , Humanos , Nefropatias/fisiopatologia , Testes de Função Renal , Masculino , Distrofia Muscular de Duchenne/fisiopatologia , Fatores de Risco , Adulto Jovem
18.
Muscle Nerve ; 61(2): 198-204, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31725915

RESUMO

INTRODUCTION: Rest-activity disruption is an important feature of Duchenne muscular dystrophy (DMD). We sought to describe sleep impairment and its relationship to quality of life (QOL) and to evaluate associations between rest-activity, sleep quality, and 6-minute walk test (6MWT) in DMD. METHODS: Sleep impairment and its relationship to QOL was assessed by questionnaire in 54 children (33 ambulatory, 21 nonambulatory) with DMD. Rest-activity characteristics were calculated for 23 of these children (14 ambulatory, nine nonambulatory) by actigraphy. RESULTS: Pathologic sleep was reported in 11 (20%) participants and correlated with lower QOL but not with ambulatory status. In ambulatory participants who completed actigraphy, rest-activity rhythm fragmentation was associated with subjective sleep impairment. Habitual daytime activity level was associated with 6MWT performance. DISCUSSION: Children with DMD experience substantial sleep impairment that is related to QOL. Wrist actigraphy may be a parsimonious tool for monitoring both sleep and motor impairment in ambulatory children with DMD.


Assuntos
Actigrafia/instrumentação , Distrofia Muscular de Duchenne/diagnóstico , Sono/fisiologia , Dispositivos Eletrônicos Vestíveis , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino , Monitorização Fisiológica , Atividade Motora , Distrofia Muscular de Duchenne/complicações , Distrofia Muscular de Duchenne/fisiopatologia , Qualidade de Vida , Transtornos do Sono-Vigília/diagnóstico , Transtornos do Sono-Vigília/etiologia , Inquéritos e Questionários , Teste de Caminhada
19.
Muscle Nerve ; 61(2): 156-162, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31650559

RESUMO

INTRODUCTION: Becker muscular dystrophy (BMD) results in decreased dystrophin with implications for mental health. METHODS: This is a retrospective case series of neurodevelopmental, behavioral, and emotional symptoms and respective pharmacotherapies of 70 patients with BMD. RESULTS: Fifty-four (77.1%) patients exhibited at least one symptom, and 19 (27.1%) patients exhibited four or more symptoms. The most prevalent symptoms were specific learning disabilities or special education needs (31.4%), inattention/hyperactivity (35.7%), language/speech delays (35.7%), and emotional or behavioral dysregulation (38.6%). Fisher's exact tests indicated that anxiety was more prevalent with mutations upstream of exon 30 (P = .049), but the prevalence of other symptoms did not differ with respect to mutation sites. Similarly, the number of symptoms individual patients with BMD exhibited did not differ with respect to mutation sites. Seventeen (24.3%) patients required pharmacotherapy to manage symptoms. DISCUSSION: Neurodevelopmental, behavioral, and emotional symptoms are prevalent in patients with BMD regardless of dystrophin gene mutation site.


Assuntos
Sintomas Afetivos/etiologia , Deficiências do Desenvolvimento/etiologia , Distrofina/genética , Distrofia Muscular de Duchenne/complicações , Adolescente , Sintomas Afetivos/patologia , Sintomas Afetivos/psicologia , Ansiedade/etiologia , Ansiedade/psicologia , Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Criança , Pré-Escolar , Deficiências do Desenvolvimento/psicologia , Feminino , Humanos , Lactente , Transtornos do Desenvolvimento da Linguagem/etiologia , Transtornos do Desenvolvimento da Linguagem/psicologia , Deficiências da Aprendizagem/etiologia , Deficiências da Aprendizagem/psicologia , Masculino , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/psicologia , Mutação , Prevalência , Estudos Retrospectivos , Adulto Jovem
20.
Cardiovasc Res ; 116(2): 368-382, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31049579

RESUMO

AIMS: Heart failure invariably affects patients with various forms of muscular dystrophy (MD), but the onset and molecular sequelae of altered structure and function resulting from full-length dystrophin (Dp427) deficiency in MD heart tissue are poorly understood. To better understand the role of dystrophin in cardiomyocyte development and the earliest phase of Duchenne muscular dystrophy (DMD) cardiomyopathy, we studied human cardiomyocytes differentiated from induced pluripotent stem cells (hiPSC-CMs) obtained from the urine of a DMD patient. METHODS AND RESULTS: The contractile properties of patient-specific hiPSC-CMs, with no detectable dystrophin (DMD-CMs with a deletion of exon 50), were compared to CMs containing a CRISPR-Cas9 mediated deletion of a single G base at position 263 of the dystrophin gene (c.263delG-CMs) isogenic to the parental line of hiPSC-CMs from a healthy individual. We hypothesized that the absence of a dystrophin-actin linkage would adversely affect myofibril and cardiomyocyte structure and function. Cardiomyocyte maturation was driven by culturing long-term (80-100 days) on a nanopatterned surface, which resulted in hiPSC-CMs with adult-like dimensions and aligned myofibrils. CONCLUSIONS: Our data demonstrate that lack of Dp427 results in reduced myofibril contractile tension, slower relaxation kinetics, and to Ca2+ handling abnormalities, similar to DMD cells, suggesting either retarded or altered maturation of cardiomyocyte structures associated with these functions. This study offers new insights into the functional consequences of Dp427 deficiency at an early stage of cardiomyocyte development in both patient-derived and CRISPR-generated models of dystrophin deficiency.


Assuntos
Cardiomiopatias/etiologia , Diferenciação Celular , Distrofina/deficiência , Células-Tronco Pluripotentes Induzidas/metabolismo , Distrofia Muscular de Duchenne/complicações , Contração Miocárdica , Miócitos Cardíacos/metabolismo , Miofibrilas/metabolismo , Sinalização do Cálcio , Cardiomiopatias/genética , Cardiomiopatias/metabolismo , Cardiomiopatias/fisiopatologia , Estudos de Casos e Controles , Linhagem Celular , Distrofina/genética , Humanos , Células-Tronco Pluripotentes Induzidas/ultraestrutura , Cinética , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/metabolismo , Distrofia Muscular de Duchenne/patologia , Miócitos Cardíacos/ultraestrutura , Miofibrilas/ultraestrutura
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