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1.
J Endocrinol Invest ; 45(3): 517-525, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34524678

RESUMEN

PURPOSE: An increased fracture risk is commonly reported in Duchenne muscular dystrophy (DMD). Our aim was to investigate bone mineral density (BMD) and bone turnover, including sclerostin, and their association with markers of cardiac and respiratory performance in a cohort of DMD subjects. METHODS: In this single center, cross sectional observational study, lumbar spine (LS) BMD Z-scores, C-terminal telopeptide of procollagen type I (CTX) and osteocalcin (BGP), as bone resorption and formation markers, respectively, and sclerostin were assessed. Left ventricular ejection fraction (LVEF) and forced vital capacity (FVC) were evaluated. Clinical prevalent fractures were also recorded. RESULTS: Thirty-one patients [median age = 14 (12-21.5) years] were studied. Ambulant subjects had higher LS BMD Z-scores compared with non-ambulant ones and subjects with prevalent clinical fractures [n = 9 (29%)] showed lower LS BMD Z-scores compared with subjects without fractures. LS BMD Z-scores were positively correlated with FVC (r = 0.50; p = 0.01), but not with glucocorticoid use, and FVC was positively associated with BGP (r = 0.55; p = 0.02). In non-ambulant subjects, LS BMD Z-scores were associated with BMI (r = 0.54; p = 0.02) and sclerostin was associated with age (r = 0.44; p = 0.05). Age, BMI, FVC and sclerostin were independently associated with LS BMD Z-score in a stepwise multiple regression analysis. Older age, lower BMI, FVC and sclerostin were associated with lower LS BMD Z-scores. CONCLUSION: In a cohort of DMD patients, our data confirm low LS BMD Z-scores, mainly in non-ambulant subjects and irrespective of the glucocorticoid use, and suggest that FVC and sclerostin are independently associated with LS BMD Z-scores.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Colágeno Tipo I/metabolismo , Fracturas Óseas , Glucocorticoides/uso terapéutico , Distrofia Muscular de Duchenne , Péptidos/metabolismo , Disfunción Ventricular Izquierda , Adolescente , Biomarcadores/metabolismo , Densidad Ósea , Remodelación Ósea , Fracturas Óseas/epidemiología , Fracturas Óseas/etiología , Fracturas Óseas/prevención & control , Humanos , Italia/epidemiología , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/patología , Limitación de la Movilidad , Distrofia Muscular de Duchenne/diagnóstico , Distrofia Muscular de Duchenne/tratamiento farmacológico , Distrofia Muscular de Duchenne/metabolismo , Distrofia Muscular de Duchenne/fisiopatología , Volumen Sistólico , Disfunción Ventricular Izquierda/diagnóstico , Disfunción Ventricular Izquierda/etiología , Capacidad Vital
2.
Ann Neurol ; 88(6): 1109-1117, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32926458

RESUMEN

OBJECTIVE: We report natural history data in a large cohort of 199 patients with spinal muscular atrophy (SMA) type III assessed using the Hammersmith Functional Motor Scale Expanded (HFMSE). The aim of the study was to establish the annual rate and possible patterns of progression according to a number of variables, such as age of onset, age at assessment, SMN2 copy number, and functional status. METHODS: HFMSE longitudinal changes were assessed using piecewise linear mixed-effects models. The dependency in the data due to repeated measures was accounted for by a random intercept per individual and an unstructured covariance R matrix was used as correlation structure. An additional descriptive analysis was performed for 123 patients, for a total of 375 12-month assessments. RESULTS: A break point at age 7 years was set for the whole cohort and for SMA IIIA and IIIB. Age, SMA type, and ambulatory status were significantly associated with changes in mean HFMSE score, whereas gender and SMN2 copy number were not. The increase in response before the break point of age 7 years is significant only for SMA IIIA (ß = 1.79, p < 0.0001). After the break point, the change in the rate of HFMSE score significantly decrease for both SMA IIIA (ß = -1.15, p < 0.0001) and IIIB (ß = -0.69, p = 0.002). INTERPRETATION: Our findings contribute to the understanding of the natural history of SMA type III and will be helpful in the interpretation of the real-world data of patients treated with commercially available drugs. ANN NEUROL 2020;88:1109-1117.


Asunto(s)
Atrofias Musculares Espinales de la Infancia/diagnóstico , Atrofias Musculares Espinales de la Infancia/genética , Adolescente , Adulto , Edad de Inicio , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Dosificación de Gen/genética , Humanos , Masculino , Modelos Neurológicos , Proteína 2 para la Supervivencia de la Neurona Motora/genética , Adulto Joven
3.
Muscle Nerve ; 64(5): 552-559, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34327716

RESUMEN

INTRODUCTION: The Hammersmith Functional Motor Scale Expanded (HFMSE) and the Revised Upper Limb Module (RULM) have been widely used in natural history studies and clinical trials. Our aim was to establish how the scales relate to each other at different age points in spinal muscular atrophy (SMA) type 2 and 3, and to describe their coherence over 12 mo. METHODS: The study was performed by cross-sectional and longitudinal reanalysis of previously published natural history data. The longitudinal analysis of the 12-mo changes also included the analysis of concordance between scales with changes grouped as stable (±2 points), improved (>+2) or declined (>-2). RESULTS: Three hundred sixty-four patients were included in the cross-sectional analysis, showing different trends in score and point of slope change for the two scales. For type 2, the point of slope change was 4.1 y for the HFMSE and 5.8 for the RULM, while for type 3, it was 6 y for the HFMSE and 7.3 for the RULM. One-hundred-twenty-one patients had at least two assessments at 12 mo. Full concordance was found in 57.3% of the assessments, and in 40.4% one scale remained stable and the other changed. Each scale appeared to be more sensitive to specific age or functional subgroups. DISCUSSION: The two scales, when used in combination, may increase the sensitivity to detect clinically meaningful changes in motor function in patients with SMA types 2 and 3.


Asunto(s)
Atrofia Muscular Espinal , Atrofias Musculares Espinales de la Infancia , Estudios Transversales , Humanos , Oligonucleótidos/uso terapéutico , Atrofias Musculares Espinales de la Infancia/tratamiento farmacológico , Extremidad Superior
4.
Neurol Sci ; 42(3): 1023-1029, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32710206

RESUMEN

Amyotrophic lateral sclerosis (ALS) is a multisystemic disease compromising both the neuromuscular system and the cognitive status. Non-invasive ventilation (NIV) has been shown to improve survival and quality of life in ALS patients with respiratory failure, but scanty literature investigated which are the predictors of NIV tolerance. The aim of this study was to evaluate the impact of functional, cognitive, neurobehavioral, and respiratory status on NIV compliance and tolerance in patients with ALS. We retrospectively evaluated clinical data of ALS patients who consecutively underwent a NIV trial during hospitalization. Cognitive and neurobehavioral assessments have been performed using the Edinburgh Cognitive and Behavioral ALS Screen (ECAS), the Hospital Anxiety and Depression Scale (HADS), the Frontal Assessment Battery (FAB), the Raven's 47 Colored Progressive Matrices (PM47), and the Neurobehavioral Rating Scale Revised (NRSR). Seventy-two patients (mean age ± SD; 63.9 ± 10.6 years) were included. Patients adapted were 63/72 (87.5%). The average time of adaptation was 7.82 ± 5.27 days. The time required to reach a satisfying NIV adaptation was significantly related to the presence of sialorrhea (p = 0.02), respiratory status (Borg Dyspnoea Scale, p = 0.006, and ALS-FRS-R respiratory subscore, p = 0.03) and behavioral and cognitive impairment (NRSR-F1, p = 0.04, NRSR- F5, p = 0.04). Presence of sialorrhea and neurobehavioral impairment, and absence of respiratory symptoms are negative predictors of NIV adaptation. This study highlights the need of a multidisciplinary patient-tailored approach including cognitive-behavioral assessment and a psychological support program to optimize patient's training and compliance to NIV.


Asunto(s)
Esclerosis Amiotrófica Lateral , Ventilación no Invasiva , Insuficiencia Respiratoria , Esclerosis Amiotrófica Lateral/complicaciones , Humanos , Calidad de Vida , Estudios Retrospectivos
5.
Int J Mol Sci ; 22(9)2021 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-33919289

RESUMEN

Spinal muscular atrophy (SMA) type 1 is a severe infantile autosomal-recessive neuromuscular disorder caused by a survival motor neuron 1 gene (SMN1) mutation and characterized by progressive muscle weakness. Without supportive care, SMA type 1 is rapidly fatal. The antisense oligonucleotide nusinersen has recently improved the natural course of this disease. Here, we investigated, with a functional proteomic approach, cerebrospinal fluid (CSF) protein profiles from SMA type 1 patients who underwent nusinersen administration to clarify the biochemical response to the treatment and to monitor disease progression based on therapy. Six months after starting treatment (12 mg/5 mL × four doses of loading regimen administered at days 0, 14, 28, and 63), we observed a generalized reversion trend of the CSF protein pattern from our patient cohort to that of control donors. Notably, a marked up-regulation of apolipoprotein A1 and apolipoprotein E and a consistent variation in transthyretin proteoform occurrence were detected. Since these multifunctional proteins are critically active in biomolecular processes aberrant in SMA, i.e., synaptogenesis and neurite growth, neuronal survival and plasticity, inflammation, and oxidative stress control, their nusinersen induced modulation may support SMN improved-expression effects. Hence, these lipoproteins and transthyretin could represent valuable biomarkers to assess patient responsiveness and disease progression.


Asunto(s)
Terapia Genética , Oligonucleótidos/farmacología , Proteoma/análisis , Atrofias Musculares Espinales de la Infancia/terapia , Preescolar , Femenino , Humanos , Lactante , Masculino , Oligonucleótidos/uso terapéutico , Oligonucleótidos Antisentido/farmacología , Oligonucleótidos Antisentido/uso terapéutico , Atrofias Musculares Espinales de la Infancia/líquido cefalorraquídeo , Atrofias Musculares Espinales de la Infancia/tratamiento farmacológico , Atrofias Musculares Espinales de la Infancia/genética
6.
Mol Cell Biochem ; 470(1-2): 189-197, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32447718

RESUMEN

In Duchenne muscular dystrophy (DMD), telomere shortening has been postulated to contribute to the failure of regenerative activity promoting the premature senescence of satellite cells. The aim of the present study was to investigate the telomere length and the expression of telomeric repeat-binding factor-1 (TRF1), poly (ADP-ribose) polymerase-1 (PARP1) and mouse telomerase reverse transcriptase (MTERT) in gastrocnemius, tibialis anterior and diaphragm muscles of the murine model of DMD, the mdx mouse and whether a chronic protocol of forced exercise impacts on them. Our results confirmed a telomere shortening in mdx muscles, more evident in the diaphragm, in which exercise induced a greater shortening than in wild-type mice. Moreover, we showed for the first time in mdx an increased TRF1 and PARP1 expression and an augmented activity of MTERT, further enhanced by exercise. These results reinforce the hypothesis that a deregulation of mechanisms involved in telomere length occurs and may pave the way for the test of compounds targeting proteins modulating telomere maintenance as a novel strategy to treat dystrophinopathies.


Asunto(s)
Distrofia Muscular de Duchenne/metabolismo , Condicionamiento Físico Animal , Poli(ADP-Ribosa) Polimerasa-1/genética , Telomerasa/genética , Telómero/metabolismo , Proteína 1 de Unión a Repeticiones Teloméricas/genética , Animales , Modelos Animales de Enfermedad , Genotipo , Ratones , Ratones Endogámicos mdx , Músculo Esquelético/metabolismo , Transducción de Señal , Acortamiento del Telómero
7.
Neurol Sci ; 41(7): 1677-1683, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32112218

RESUMEN

Newborn screening (NBS) is an essential, preventive public health programme for early identification of disorders whose early treatment can lead to significant reduction in morbidity and mortality. NBS for Duchenne muscular dystrophy (DMD) has been a controversial matter for many years, because of false positives, the lack of effective drugs and the need of more data about screening efficacy. The still high diagnostic delay of DMD and the current availability of drugs such as steroid, ataluren, eteplirsen, golodirsen and forthcoming new drugs, improving the clinical conditions if early started, make appropriate to begin a concrete discussion between stakeholders to identify best practice for DMD screening. A two-step system CK/DNA screening programme is presented to be performed in male infants aged between 6 months and 42 months involving more than 30,000 male infants. Five to eight DMD subjects are believed to be diagnosed. The pilot project would give the opportunity to test in a small population the feasibility of an infant screening programme, which in the near future could be applicable to an entire country.


Asunto(s)
Distrofia Muscular de Duchenne , Diagnóstico Tardío , Humanos , Lactante , Recién Nacido , Masculino , Distrofia Muscular de Duchenne/diagnóstico , Distrofia Muscular de Duchenne/genética , Tamizaje Neonatal , Oligonucleótidos , Proyectos Piloto
8.
Neurol Sci ; 41(3): 497-508, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31792719

RESUMEN

Many neurological diseases may cause acute respiratory failure (ARF) due to involvement of bulbar respiratory center, spinal cord, motoneurons, peripheral nerves, neuromuscular junction, or skeletal muscles. In this context, respiratory emergencies are often a challenge at home, in a neurology ward, or even in an intensive care unit, influencing morbidity and mortality. More commonly, patients develop primarily ventilatory impairment causing hypercapnia. Moreover, inadequate bulbar and expiratory muscle function may cause retained secretions, frequently complicated by pneumonia, atelectasis, and, ultimately, hypoxemic ARF. On the basis of the clinical onset, two main categories of ARF can be identified: (i) acute exacerbation of chronic respiratory failure, which is common in slowly progressive neurological diseases, such as movement disorders and most neuromuscular diseases, and (ii) sudden-onset respiratory failure which may develop in rapidly progressive neurological disorders including stroke, convulsive status epilepticus, traumatic brain injury, spinal cord injury, phrenic neuropathy, myasthenia gravis, and Guillain-Barré syndrome. A tailored assistance may include manual and mechanical cough assistance, noninvasive ventilation, endotracheal intubation, invasive mechanical ventilation, or tracheotomy. This review provides practical recommendations for prevention, recognition, management, and treatment of respiratory emergencies in neurological diseases, mostly in teenagers and adults, according to type and severity of baseline disease.


Asunto(s)
Urgencias Médicas , Intubación Intratraqueal , Enfermedades del Sistema Nervioso/complicaciones , Respiración Artificial , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/terapia , Traqueotomía , Humanos
9.
Neurol Sci ; 41(9): 2561-2567, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32246354

RESUMEN

Previous studies demonstrated the benefits of motor exercise and physical activity in neuromuscular disorders. However, very few papers assessed the effects of sport practise. The aim of this multicentre study was to assess the impact of sport activity on self-esteem and emotional regulation in a cohort of athletes with neuromuscular disorders. The 38 patients with Duchenne, Becker or other types of muscular dystrophy or spinal muscular atrophy practising sport (aged 13-49 years) and 39 age-, gender-, disability- and disease-matched patients not practising sport were enrolled. Testing procedures to assess self-esteem, anxiety and depression disorder, personality trait and quality of life (QoL) were used. Patients practising sport had a significantly higher self-esteem, lower level of depression, greater social own identity and adherence and QoL. Frequency of sport activity may represent a complementary therapy in neuromuscular disorders to improve mental and social well-being.


Asunto(s)
Enfermedades Neuromusculares , Deportes , Adolescente , Adulto , Atletas , Humanos , Persona de Mediana Edad , Enfermedades Neuromusculares/terapia , Calidad de Vida , Autoimagen , Adulto Joven
10.
Neurol Sci ; 40(4): 671-681, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30805745

RESUMEN

This is the second part of a two-part document intended to discuss recent therapeutic progresses in genetic neuromuscular disorders. The present review is for diseases of motor neuron and skeletal muscle, some of which reached recently the most innovative therapeutic approaches. Nusinersen, an SMN2 mRNA splicing modifier, was approved as first-ever therapy of spinal muscular atrophy (SMA) by FDA in 2016 and by EMA in 2017. The orally administered small-molecule risdiplam, which increases SMN protein levels similarly but also in peripheral organs, is tested in ongoing phase 2 and 3 trials. After positive results with phase 1 treatment with AAV9-SMN, the first gene therapy for SMA, a phase 3 clinical trial is ongoing. Ataluren is the first approved drug for Duchenne muscular dystrophy (DMD) patients with premature stop codon mutations and its indication has been recently extended since the age of 2 years. Exon skipping technology was and is currently tested in many phase 3 trials, and eteplirsen received a conditional approval by FDA for patients amenable to exon 51 skipping, but not by EMA. Many other compounds with different mechanisms of action are now tested in DMD by phase 2 and 3 trials, including phase 1 gene therapy. Other innovative approaches are under investigation, i.e., gene therapy in X-linked myotubular myopathy and Pompe disease, and antisense oligonucleotides in myotonic dystrophy type 1. Positive evidences are discussed about lamotrigine and ranolazine in non-dystrophic myotonias, chaperons in Pompe disease, and nucleosides in mitochondrial DNA depletion induced by thymidine kinase 2 deficiency.


Asunto(s)
Terapia Genética/métodos , Enfermedad del Almacenamiento de Glucógeno Tipo II/terapia , Enfermedades Mitocondriales/terapia , Atrofia Muscular Espinal/terapia , Enfermedades Musculares/terapia , Distrofia Muscular de Duchenne/terapia , Miopatías Estructurales Congénitas/terapia , Distrofia Miotónica/terapia , Fármacos Neuromusculares/uso terapéutico , Oligonucleótidos/uso terapéutico , Oxadiazoles/uso terapéutico , Proteínas del Complejo SMN , Humanos
11.
Neurol Sci ; 40(4): 661-669, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30847674

RESUMEN

Recent advances in pathophysiological and genetic mechanisms of some neuromuscular diseases and a rapid progress in new pharmacological technologies led to an accelerated development of innovative treatments, generating an unexpected therapeutic revolution. In part 1, we report already commercially available drugs, just approved drugs and new therapeutic promises in the treatment of peripheral neuropathies. Hereditary transthyretin amyloidosis (hATTR) is a devastating disease due to amyloid accumulation in peripheral nerves, heart and autonomic system. The first specific drug approved for hATTR was tafamidis, a TTR tetramer stabilizer. In 2018, the positive results of two phase 3 trials have been reported leading to start of regulatory approval route for inotersen, an antisense oligonucleotide and patisiran, the first-ever RNA interference (RNAi) therapeutic. System biology targeting approach has indicated baclofen, naltrexone and sorbitol in combination (PXT3003) as candidate drugs for Charcot-Marie-Tooth disease type 1A. This hypothesis was confirmed in experimental models and in phase 2 and 3 clinical trials. Givosiran, another RNAi therapeutic, targeting 5-aminolevulinic acid synthase, has been positively tested in acute intermittent porphyria in phase 1/2 and ongoing phase 3 trials. Although allogenic hematopoietic stem cell transplantation resulted recently a long-term therapy in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), a new strategy is liver transplantation which is able to revert the severe biochemical and clinical imbalance of the disease. Recently, a gene therapy has been tested in a MNGIE murine model, indicating that it may become a new therapeutic option.


Asunto(s)
Neuropatías Amiloides Familiares/terapia , Enfermedad de Charcot-Marie-Tooth/terapia , Seudoobstrucción Intestinal/terapia , Distrofia Muscular Oculofaríngea/terapia , Porfiria Intermitente Aguda/terapia , Tratamiento con ARN de Interferencia/métodos , Humanos , Oftalmoplejía/congénito
12.
Neurol Sci ; 39(11): 1837-1845, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30218397

RESUMEN

INTRODUCTION: Duchenne muscular dystrophy (DMD) is a devastating, progressive neuromuscular disorder for which there is no cure. As the dystrophin gene is located on the X chromosome, DMD occurs predominately in males. DMD is caused by a lack of functional dystrophin protein resulting from mutations in the 2.2-Mb DMD gene, whichdisrupts the reading frame. Care considerations for DMD advocate a coordinated, multidisciplinary approach to the management of DMD in order to optimize management of the primary manifestations of DMD as well as any secondary complications that may arise. METHODS: This review provides an overview of the multidisciplinary clinical management of DMD with regard to the respiratory, cardiology, orthopedic, and nutritional needs of patients with DMD. Recent advances in novel disease-modifying treatments for DMD are also discussed with specific reference to exon skipping and suppression of premature stop codons as promising genetic therapies. RESULTS: The combination of multidisciplinary clinical management alongside novel gene therapiesoffers physicians a powerful armamentarium for the treatment of DMD.


Asunto(s)
Distrofia Muscular de Duchenne/terapia , Manejo de la Enfermedad , Humanos , Distrofia Muscular de Duchenne/diagnóstico
13.
Neurol Sci ; 39(11): 1961-1964, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30043247

RESUMEN

Nusinersen is the first approved drug to treat spinal muscular atrophy (SMA). Its periodic intrathecal delivery may cause psychological burden in infants and in their parents. We report our experience during expanded access program (EAP) for type 1 SMA in a single Italian center. Because of the occurrence of stress emotional states, anxious reactions and fear before, during, and after lumbar puncture (LP), a specific psychological intervention was implemented based on regulation of emotions, anticipatory expectations, and post-event attributions. Activities included the use of fairy tales, distraction, music play through listening preferred cartoon themes in the youngest children, and contextual games and solution of fun riddle quizzes in the oldest ones. State anxiety greatly reduced in children and their parents. Treatment of psychological aspects should therefore become an integral part of health care in SMA infants and children during Nusinersen treatment.


Asunto(s)
Oligonucleótidos Antisentido/administración & dosificación , Oligonucleótidos/administración & dosificación , Atrofias Musculares Espinales de la Infancia/tratamiento farmacológico , Atrofias Musculares Espinales de la Infancia/psicología , Adolescente , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Inyecciones Espinales/métodos , Italia , Masculino , Resultado del Tratamiento
15.
Muscle Nerve ; 52(1): 13-21, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25363165

RESUMEN

INTRODUCTION: This study explores burden and social and professional support in families of young patients with muscular dystrophies (MDs) in Italy. METHODS: The study was carried out on 502 key relatives of 4- to 25-year-old patients suffering from Duchenne, Becker, or Limb-Girdle MD who were living with at least 1 adult relative. RESULTS: A total of 77.1% of relatives reported feelings of loss, 74.0% had feelings of sadness, and 59.1% had constraints in leisure activities. Burden was higher among relatives of patients with higher disability and who spent more daily hours in caregiving. Practical difficulties were higher among relatives who perceived lower help in patient emergencies and less practical support by their social network. Psychological burden was higher in those relatives who were unemployed, those with poorer support in emergencies, and those with lower social contacts. CONCLUSIONS: Caring for patients with MDs may be demanding for relatives even in the early stages of these disorders, especially when social support is poor and the patient's disability increases.


Asunto(s)
Familia/psicología , Distrofias Musculares/economía , Distrofias Musculares/epidemiología , Relaciones Profesional-Paciente , Apoyo Social , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Distrofias Musculares/terapia , Análisis de Regresión , Factores Socioeconómicos , Encuestas y Cuestionarios , Adulto Joven
16.
Acta Myol ; 33(3): 136-43, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25873782

RESUMEN

This study explored the burden in parents and healthy siblings of 4-17 year-old patients with Duchenne (DMD) and Becker (BMD) muscular dystrophies, and whether the burden varied according to clinical aspects and social resources. Data on socio-demographic characteristics, patient's clinical history, parent and healthy children burden, and on parent's social resources were collected using self-reported questionnaires administered to 336 parents of patients with DMD (246) and BMD (90). Parents of patients with DMD reported higher burden than those of patients with BMD, especially concerning feeling of loss (84.3% DMD vs. 57.4% BMD), stigma (44.2% DMD vs. 5.5% BMD) and neglect of hobbies (69.0% DMD vs. 32.5% BMD). Despite the burden, 66% DMD and 62.4% BMD parents stated the caregiving experience had a positive impact on their lives. A minority of parents believed MD has a negative influence on the psychological well-being (31.0% DMD vs. 12.8% BMD), and social life of unaffected children (25.7% vs. 18.4%). In the DMD group, burden correlated with duration of illness and parent age, and burden was higher among parents with lower social contacts and support in emergencies. In DMD, difficulties among healthy children were reported as higher by parents who were older, had higher burden and lower social contacts. In both groups, burden increased in relation to patient disability. These findings underline that the psychological support to be provided to parents of patients with MD, should take into account clinical features of the disease.


Asunto(s)
Cuidadores , Salud de la Familia , Distrofia Muscular de Duchenne , Padres/psicología , Hermanos/psicología , Adolescente , Adulto , Cuidadores/psicología , Cuidadores/estadística & datos numéricos , Niño , Preescolar , Costo de Enfermedad , Familia , Humanos , Italia , Persona de Mediana Edad , Distrofia Muscular de Duchenne/fisiopatología , Distrofia Muscular de Duchenne/psicología , Apoyo Social , Factores Socioeconómicos
17.
Neuromuscul Disord ; 34: 75-82, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38157655

RESUMEN

Duchenne muscular dystrophy (DMD) is a neuromuscular condition characterized by muscle weakness. The Performance of upper limb (PUL) test is designed to evaluate upper limb function in DMD patients across three domains. The aim of this study is to identify frequently lost or gained PUL 2.0 abilities at distinct functional stages in DMD patients. This retrospective study analyzed prospectively collected data on 24-month PUL 2.0 changes related to ambulatory function. Ambulant patients were categorized based on initial 6MWT distance, non-ambulant patients by time since ambulation loss. Each PUL 2.0 item was classified as shift up, no change, or shift down. The study's cohort incuded 274 patients, with 626 paired evaluations at the 24-month mark. Among these, 55.1 % had activity loss, while 29.1 % had gains. Ambulant patients showed the lowest loss rates, mainly in the shoulder domain. The highest loss rate was in the shoulder domain in the transitioning subgroup and in elbow and distal domains in the non-ambulant patients. Younger ambulant patients demonstrated multiple gains, whereas in the other functional subgroups there were fewer gains, mostly tied to singular activities. Our findings highlight divergent upper limb domain progression, partly linked to functional status and baseline function.


Asunto(s)
Distrofia Muscular de Duchenne , Humanos , Distrofia Muscular de Duchenne/complicaciones , Estudios Retrospectivos , Extremidad Superior , Caminata , Debilidad Muscular
18.
J Neuromuscul Dis ; 11(2): 285-297, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38363615

RESUMEN

Background: Dilated cardiomyopathy (DCM) is a major complication of, and leading cause of mortality in Duchenne muscular dystrophy (DMD). Its severity, age at onset, and rate of progression display wide variability, whose molecular bases have been scarcely elucidated. Potential DCM-modifying factors include glucocorticoid (GC) and cardiological treatments, DMD mutation type and location, and variants in other genes. Methods and Results: We retrospectively collected 3138 echocardiographic measurements of left ventricular ejection fraction (EF), shortening fraction (SF), and end-diastolic volume (EDV) from 819 DMD participants, 541 from an Italian multicentric cohort and 278 from the Cooperative International Neuromuscular Group Duchenne Natural History Study (CINRG-DNHS). Using generalized estimating equation (GEE) models, we estimated the yearly rate of decrease of EF (-0.80%) and SF (-0.41%), while EDV increase was not significantly associated with age. Utilizing a multivariate generalized estimating equation (GEE) model we observed that mutations preserving the expression of the C-terminal Dp71 isoform of dystrophin were correlated with decreased EDV (-11.01 mL/m2, p = 0.03) while for dp116 were correlated with decreased EF (-4.14%, p = <0.001). The rs10880 genotype in the LTBP4 gene, previously shown to prolong ambulation, was also associated with increased EF and decreased EDV (+3.29%, p = 0.002, and -10.62 mL/m2, p = 0.008) with a recessive model. Conclusions: We quantitatively describe the progression of systolic dysfunction progression in DMD, confirm the effect of distal dystrophin isoform expression on the dystrophin-deficient heart, and identify a strong effect of LTBP4 genotype of DCM in DMD.


Asunto(s)
Cardiomiopatías , Distrofia Muscular de Duchenne , Humanos , Distrofina/genética , Distrofina/metabolismo , Haplotipos , Estudios Retrospectivos , Volumen Sistólico , Función Ventricular Izquierda , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/complicaciones , Cardiomiopatías/etiología , Cardiomiopatías/genética , Isoformas de Proteínas/genética , Proteínas de Unión a TGF-beta Latente/genética
19.
J Neuromuscul Dis ; 10(4): 567-574, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37066919

RESUMEN

BACKGROUND: The performance of upper limb 2.0 (PUL) is widely used to assess upper limb function in DMD patients. The aim of the study was to assess 24 month PUL changes in a large cohort of DMD patients and to establish whether domains changes occur more frequently in specific functional subgroups. METHODS: The PUL was performed in 311 patients who had at least one pair of assessments at 24 months, for a total of 808 paired assessments. Ambulant patients were subdivided according to the ability to walk: >350, 250-350, ≤250 meters. Non ambulant patients were subdivided according to the time since they lost ambulation: <1, 1-2, 2-5 or >5 years. RESULTS: At 12 months, the mean PUL 2.0 change on all the paired assessments was -1.30 (-1.51--1.05) for the total score, -0.5 (-0.66--0.39) for the shoulder domain, -0.6 (-0.74--0.5) for the elbow domain and -0.1 (-0.20--0.06) for the distal domain.At 24 months, the mean PUL 2.0 change on all the paired assessments was -2.9 (-3.29--2.60) for the total score, -1.30 (-1.47--1.09) for the shoulder domain, -1.30 (-1.45--1.11) for the elbow domain and -0.4 (-1.48--1.29) for the distal domain.Changes at 12 and 24 months were statistically significant between subgroups with different functional abilities for the total score and each domain (p < 0.001). CONCLUSION: There were different patterns of changes among the functional subgroups in the individual domains. The time of transition, including the year before and after loss of ambulation, show the peak of negative changes in PUL total scores that reflect not only loss of shoulder but also of elbow activities. These results suggest that patterns of changes should be considered at the time of designing clinical trials.


Asunto(s)
Distrofia Muscular de Duchenne , Humanos , Actividades Cotidianas , Extremidad Superior , Caminata
20.
Skeletal Radiol ; 41(8): 955-61, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22069033

RESUMEN

PURPOSE: To examine the usefulness of dual-echo dual-flip angle spoiled gradient recalled (SPGR) magnetic resonance imaging (MRI) technique in quantifying muscle fat fraction (MFF) of pelvic and thighs muscles as a marker of disease severity in boys with Duchenne muscular dystrophy (DMD), by correlating MFF calculation with clinical assessments. We also tried to identify characteristic patterns of disease distribution. MATERIALS AND METHODS: Twenty consecutive boys (mean age, 8.6 years ± 2.3 [standard deviation, SD]; age range, 5-15 years; median age, 9 years;) with DMD were evaluated using a dual-echo dual-flip angle SPGR MRI technique, calculating muscle fat fraction (MFF) of eight muscles in the pelvic girdle and thigh (gluteus maximus, adductor magnus, rectus femoris, vastus lateralis, vastus medialis, biceps femoris, semitendinosus, and gracilis). Color-coded parametric maps of MFF were also obtained. A neurologist who was blinded to the MRI findings performed the clinical assessments (patient age, Medical Research Council score, timed Gower score, time to run 10 m). The relationships between mean MFF and clinical assessments were investigated using Spearman's rho coefficient. Positive and negative correlations were evaluated and considered significant if the P value was < 0.05. RESULTS: The highest mean MFF was found in the gluteus maximus (mean, 46.3 % ± 24.5 SD), whereas the lowest was found in the gracilis muscle (mean, 2.7 % ± 4.7 SD). Mean MFF of the gluteus maximus was significantly higher than that of the other muscles (P < 0.01), except for the adductor magnus and biceps muscles. A significant positive correlation was found between the mean MFF of all muscles and the patients age (20 patients; P < 0.005), Medical Research Council score (19 patients; P < 0.001), timed Gower score (17 patients; P < 0.03), and time to run 10 m (20 patients; P < 0.001). A positive correlation was also found between the mean MFF of the gluteus maximus muscle and the timed Gower score. Color-coded maps provided an efficient visual assessment of muscle fat content and its heterogeneous distribution. CONCLUSION: Muscle fat fraction calculation and mapping using the dual-echo dual-flip angle SPGR MRI technique are useful markers of disease severity and permit patterns of disease distribution to be identified in patients with DMD.


Asunto(s)
Tejido Adiposo/patología , Adiposidad , Imagen por Resonancia Magnética/métodos , Músculo Esquelético/patología , Distrofia Muscular de Duchenne/diagnóstico , Adolescente , Niño , Femenino , Humanos , Masculino , Pelvis , Proyectos Piloto , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Estadística como Asunto , Muslo
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