RESUMO
Facioscapulohumeral muscular dystrophy (FSHD) is an exclusively human neuromuscular disease. In the last decades the cause of FSHD was identified: the loss of epigenetic repression of the D4Z4 repeat on chromosome 4q35 resulting in inappropriate transcription of DUX4. This is a consequence of a reduction of the array below 11 units (FSHD1) or of a mutation in methylating enzymes (FSHD2). Both require the presence of a 4qA allele and a specific centromeric SSLP haplotype. Muscles become involved in a rostro-caudally order with an extremely variable progression rate. Mild disease and non-penetrance in families with affected individuals is common. Furthermore, 2% of the Caucasian population carries the pathological haplotype without clinical features of FSHD.In order to explain the various features of FSHD we applied Ockham's Razor to all possible scenarios and removed unnecessary complexities. We postulate that early in embryogenesis a few cells escape epigenetic silencing of the D4Z4 repeat. Their number is assumed to be roughly inversely related to the residual D4Z4 repeat size. By asymmetric cell division, they produce a rostro-caudal and medio-lateral decreasing gradient of weakly D4Z4-repressed mesenchymal stem cells. The gradient tapers towards an end as each cell-division allows renewed epigenetic silencing. Over time, this spatial gradient translates into a temporal gradient based on a decreasing number of weakly silenced stem cells. These cells contribute to a mildly abnormal myofibrillar structure of the fetal muscles. They also form a downward tapering gradient of epigenetically weakly repressed satellite cells. When activated by mechanical trauma, these satellite cells de-differentiate and express DUX4. When fused to myofibrils they contribute to muscle cell death in various ways. Over time and dependent on how far the gradient reaches the FSHD phenotype becomes progressively manifest. We thus hypothesize FSHD to be a myodevelopmental disease with a lifelong attempt to restore DUX4 repression.
Assuntos
Distrofia Muscular Facioescapuloumeral , Humanos , Distrofia Muscular Facioescapuloumeral/genética , Distrofia Muscular Facioescapuloumeral/patologia , Epigênese Genética , Mutação , FenótipoRESUMO
OBJECTIVE: To evaluate facial weakness in patients with FSHD to better define clinical signs, and pilot a facial weakness severity score. METHODS: 87 FSHD patients and 55 controls were video recorded while performing seven facial tasks. The videos were assessed by three independent examiners to compile an overview of signs of facial weakness. Next, videos were semi-quantitatively assessed using a newly developed 4-point facial weakness score (FWS). This score was evaluated and correlated to other FSHD disease characteristics. RESULTS: Patients had lower scores on the total FWS than controls (mean score 43 ± 28, range 4-118, vs 14 ± 9, range 0-35, p < 0.001) and on all seven individual facial tasks (all p < 0.001). 54% of patients had FWS scores outside the range of controls. Patients had more asymmetry between the left and right side of the face than controls. About 10% of the patients had very mild facial weakness. These were mostly males (89%) with longer D4Z4 repeat sizes of 7-9 units. More severe facial weakness correlated to more severe overall disease severity and shorter D4Z4 repeat size, but not to disease duration. Interobserver agreement for the FWS between three raters was low with a Fleiss Kappa of 0.437. CONCLUSION: This study provides an overview of the clinical spectrum of facial weakness and its relation to other disease characteristics. The 4-point scale we introduced to grade the severity of facial weakness enables correlation of facial weakness to disease characteristics, but is not suited as clinical outcome measure for longitudinal studies.
Assuntos
Distrofia Muscular Facioescapuloumeral , Face , Feminino , Humanos , Estudos Longitudinais , Masculino , Distrofia Muscular Facioescapuloumeral/complicações , Distrofia Muscular Facioescapuloumeral/diagnóstico , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: To study scapular winging or other forms of scapular dyskinesis (condition of alteration of the normal position and motion of the scapula) in myotonic dystrophy type 1 (DM1), which is generally considered to be a distal myopathy, we performed an observational cohort study. METHODS: We performed a prospective cohort study on the clinical features and progression over time of 33 patients with DM1 and pronounced, mostly asymmetric scapular winging or other forms of scapular dyskinesis. We also explored if scapular dyskinesis in DM1 has the same genetic background as in facioscapulohumeral muscular dystrophy type 1 (FSHD1). RESULTS: The cohort included patients with congenital (n = 3), infantile (n = 6) and adult-onset DM1 (n = 24). Scapular girdle examination showed moderate shoulder girdle weakness (mean MRC 3) and atrophy of trapezius, infraspinatus, and rhomboid major, seemingly similar as in FSHD1. Shoulder abduction and forward flexion were limited (50-70°). In five patients, scapular dyskinesis was the initial disease symptom; in the others it appeared 1-24 years after disease onset. Follow-up data were available in 29 patients (mean 8 years) and showed mild to severe increase of scapular dyskinesis over time. In only three patients, DM1 coexisted with a FSHD mutation. In all other patients, FSHD was genetically excluded. DM2 was genetically excluded in nine patients. The clinical features of the patients with both DM1 and FSHD1 mutations were similar to those with DM1 only. CONCLUSION: Scapular dyskinesis can be considered to be part of DM1 in a small proportion of patients. In spite of the clinical overlap, FSHD can explain scapular dyskinesis only in a small minority. This study is expected to improve the recognition of shoulder girdle involvement in DM1, which will contribute to the management of these patients.
Assuntos
Progressão da Doença , Discinesias/fisiopatologia , Distrofia Miotônica/fisiopatologia , Escápula/fisiopatologia , Adulto , Idade de Início , Idoso , Discinesias/classificação , Discinesias/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Distrofia Muscular Facioescapuloumeral/complicações , Distrofia Muscular Facioescapuloumeral/genética , Distrofia Muscular Facioescapuloumeral/fisiopatologia , Distrofia Miotônica/complicações , Distrofia Miotônica/genética , Estudos Prospectivos , Índice de Gravidade de Doença , Adulto JovemRESUMO
To test the hypothesis that wheelchair dependency and (kypho-)scoliosis are risk factors for developing respiratory insufficiency in facioscapulohumeral muscular dystrophy, we examined 81 patients with facioscapulohumeral muscular dystrophy 1 of varying degrees of severity ranging from ambulatory patients to wheelchair-bound patients. We examined the patients neurologically and by conducting pulmonary function tests: Forced Vital Capacity, Forced Expiratory Volume in 1 second, and static maximal inspiratory and expiratory mouth pressures. We did not find pulmonary function test abnormalities in ambulant facioscapulohumeral muscular dystrophy patients. Even though none of the patients complained of respiratory dysfunction, mild to severe respiratory insufficiency was found in more than one third of the wheelchair-dependent patients. Maximal inspiratory pressures and maximal expiratory pressures were decreased in most patients, with a trend that maximal expiratory pressures were more affected than maximal inspiratory pressures. Wheelchair-dependent patients with (kypho-)scoliosis showed the most restricted lung function. Wheelchair-dependent patients with (kypho-)scoliosis are at risk for developing respiratory function impairment. We advise examining this group of facioscapulohumeral muscular dystrophy patients periodically, even in the absence of symptoms of respiratory insufficiency, given its frequency and impact on daily life and the therapeutic consequences.
Assuntos
Distrofia Muscular Facioescapuloumeral/fisiopatologia , Insuficiência Respiratória/fisiopatologia , Adulto , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Cifose/complicações , Cifose/epidemiologia , Cifose/fisiopatologia , Masculino , Pessoa de Meia-Idade , Distrofia Muscular Facioescapuloumeral/epidemiologia , Testes de Função Respiratória , Insuficiência Respiratória/epidemiologia , Insuficiência Respiratória/etiologia , Fatores de Risco , Escoliose/diagnóstico , Escoliose/epidemiologia , Escoliose/fisiopatologia , Cadeiras de Rodas/estatística & dados numéricosRESUMO
To better understand postural and movement disabilities, the pattern of total body muscle fat infiltration was analyzed in a large group of patients with facioscapulohumeral muscular dystrophy. Additionally, we studied whether residual D4Z4 repeat array length adjusted for age and gender could predict the degree of muscle involvement. Total body computed tomography scans of 70 patients were used to assess the degree of fat infiltration of 42 muscles from neck to ankle level on a semi-quantitative scale. Groups of muscles that highly correlated regarding fat infiltration were identified using factor analysis. Linear regression analysis was performed using muscle fat infiltration as the dependent variable and D4Z4 repeat length and age as independent variables. A pattern of muscle fat infiltration in facioscapulohumeral muscular dystrophy could be constructed. Trunk muscles were most frequently affected. Of these, back extensors were more frequently affected than previously reported. Asymmetry in muscle involvement was seen in 45% of the muscles that were infiltrated with fat. The right-sided upper extremity showed significantly higher scores for fat infiltration compared to the left side, which could not be explained by handedness. It was possible to explain 29% of the fat infiltration based on D4Z4 repeat length, corrected for age and gender. Based on our results we conclude that frequent involvement of fat infiltration in back extensors, in addition to the abdominal muscles, emphasizes the extent of trunk involvement, which may have a profound impact on postural control even in otherwise mildly affected patients.
Assuntos
Músculo Esquelético/diagnóstico por imagem , Distrofia Muscular Facioescapuloumeral/diagnóstico por imagem , Tecido Adiposo/diagnóstico por imagem , Adulto , Fatores Etários , Análise Fatorial , Feminino , Humanos , Modelos Lineares , Masculino , Força Muscular , Músculo Esquelético/fisiopatologia , Distrofia Muscular Facioescapuloumeral/genética , Distrofia Muscular Facioescapuloumeral/fisiopatologia , Fatores Sexuais , Tomografia Computadorizada por Raios X , Imagem Corporal TotalRESUMO
OBJECTIVE: In some 5% of patients with facioscapulohumeral muscular dystrophy (FSHD), no D4Z4 repeat contraction on chromosome 4q35 is observed. Such patients, termed patients with FSHD2, show loss of DNA methylation and heterochromatin markers at the D4Z4 repeat that are similar to patients with D4Z4 contractions (FSHD1). This commonality suggests that a change in D4Z4 chromatin structure unifies FSHD1 and FSHD2. The aim of our study was to critically evaluate the clinical features in patients with FSHD2 in order to establish whether these patients are phenotypically identical to FSHD1 and to establish the effects of the (epi-) genotype on the phenotype. METHODS: This cross-sectional study studied 33 patients with FSHD2 from 27 families, the largest cohort described to date. All patients were clinically assessed using a standardized clinical evaluation form. Genotype analysis was performed by pulsed field gel electrophoresis and PCR; D4Z4 methylation was studied by methylation-sensitive Southern blot analysis. RESULTS: FSHD2 is identical to FSHD1 in its clinical presentation. Notable differences include a higher incidence (67%) of sporadic cases and the absence of gender differences in disease severity in FSHD2. Overall, average disease severity in FSHD2 was similar to that reported in FSHD1 and was not influenced by D4Z4 repeat size. In FSHD2, a small effect of the degree of hypomethylation on disease severity was observed. CONCLUSIONS: Clinically, patients with FSHD2 are indistinguishable from patients with FSHD1. The present data suggest that FSHD1 and FSHD2 are the result of the same pathophysiologic process.
Assuntos
Distrofia Muscular Facioescapuloumeral/genética , Distrofia Muscular Facioescapuloumeral/fisiopatologia , Proteínas Nucleares/genética , Adolescente , Adulto , Criança , Pré-Escolar , Cromossomos Humanos Par 4 , Estudos de Coortes , Estudos Transversais , Metilação de DNA/genética , Expansão das Repetições de DNA/genética , Saúde da Família , Feminino , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Proteínas dos Microfilamentos , Pessoa de Meia-Idade , Fenótipo , Polimorfismo Genético/genética , Proteínas de Ligação a RNA , Adulto JovemRESUMO
We present a comprehensive report of two siblings with hereditary inclusion body myopathy (HIBM). The clinical features and histological characteristics of the muscle biopsies showed the typical pattern of predominantly distal vacuolar myopathy with quadriceps sparing. This was confirmed by muscle MRI. PNA lectin staining showed an increased signal at the sarcolemma in patient muscle sections compared to control muscle, indicating reduced sialylation of glycoconjugates. Mutation analysis revealed compound heterozygous mutations in the GNE gene, encoding the key enzyme in sialic acid synthesis UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase: a missense mutation (c.2086G > A; p.V696M) previously described in HIBM patients of Indian origin, and a novel frame shift mutation (c.1295delA; p.K432RfsX17) leading to a premature stopcodon. These findings confirmed the diagnosis of HIBM on the histological, molecular and biochemical level.
Assuntos
Complexos Multienzimáticos/genética , Miosite de Corpos de Inclusão/genética , Miosite de Corpos de Inclusão/patologia , Adulto , Análise Mutacional de DNA , Feminino , Mutação da Fase de Leitura , Humanos , Focalização Isoelétrica , Imageamento por Ressonância Magnética , Masculino , Músculo Esquelético/enzimologia , Músculo Esquelético/patologia , Miosite de Corpos de Inclusão/fisiopatologia , Neuraminidase , Aglutinina de Amendoim , Reação em Cadeia da Polimerase , IrmãosRESUMO
Facioscapulohumeral muscular dystrophy (FSHD) is characterized by asymmetric dysfunctioning of individual muscles. Currently, it is unknown why specific muscles are affected before others and more particularly what pathophysiology is causing this differential progression. The aim of our study was to use a combination of (31)P magnetic resonance spectroscopic imaging (MRSI) and T1-weighted MRI to uncover metabolic differences in fat infiltrated and not fat infiltrated muscles in patients with FSHD. T1-weighted images and 3D (31)P MRSI were obtained from the calf muscles of nine patients with diagnosed FSHD and nine healthy age and sex matched volunteers. Muscles of patients were classified as fat infiltrated (PFM) and non fat-infiltrated (PNM) based on visual assessment of the MR images. Ratios of phosphocreatine (PCr), phosphodiesters (PDE) and inorganic phosphate (Pi) over ATP and tissue pH were compared between PFM and PNM and the same muscles in healthy volunteers. Of all patients, seven showed moderate to severe fatty infiltration in one or more muscles. In these muscles, decreases in PCr/ATP and increases in tissue pH were observed compared to the same muscles in healthy volunteers. Interestingly, these differences were absent in the PNM group. Our data show that differences in metabolite ratios and tissue pH in skeletal muscle between healthy volunteers and patients with FSHD appear to be specific for fat infiltrated muscles. Normal appearing muscles on T1 weighted images of patients showed normal phosphoryl metabolism, which suggests that in FSHD disease progression is truly muscle specific.
Assuntos
Metabolismo Energético/fisiologia , Perna (Membro)/anatomia & histologia , Perna (Membro)/patologia , Músculo Esquelético , Distrofia Muscular Facioescapuloumeral , Adulto , Idoso , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Distrofia Muscular Facioescapuloumeral/metabolismo , Distrofia Muscular Facioescapuloumeral/patologia , Distrofia Muscular Facioescapuloumeral/fisiopatologia , Adulto JovemRESUMO
Facioscapulohumeral muscular dystrophy is clinically mainly characterized by progressive weakness of the facial, shoulder and upper arm muscles. It is an autosomal dominant heriditary disease, caused by a contraction of a repetitive DNA element at the end of the long arm of chromosome 4. This contraction causes the local relaxation of the chromatin structure and likely dysregulation of one or more genes. Oral health care providers can play a significant role in the early recognition, as the often asymmetric facial weakness is frequently the first symptom. Adequate oral health care is needed because of the facial weakness.
Assuntos
Cromossomos Humanos Par 4/genética , Odontologia/métodos , Distrofia Muscular Facioescapuloumeral/genética , Distrofia Muscular Facioescapuloumeral/fisiopatologia , Aberrações Cromossômicas , Genes Dominantes , HumanosRESUMO
BACKGROUND AND AIMS: Muscle weakness is a potentially important, yet poorly studied, risk factor for falls. Detailed studies of patients with specific myopathies may shed new light on the relation between muscle weakness and falls. Here falls in patients with facioscapulohumeral disease (FSHD) who suffered from lower limb muscle weakness were examined. This study provides insights into the prevalence, relevance and pathophysiology of falls in FSHD. METHODS: A validated questionnaire was used as well as a prospective 3 month follow-up to examine the prevalence, circumstances and consequences of falls in 73 patients with FSHD and 49 matched healthy controls. In a subgroup of 28 subjects, muscle strength was also examined and balance was assessed electrophysiologically using body worn gyroscopes. RESULTS: In the questionnaire, 30% of the patients reported falling at least once a month whereas none of the controls did. Injuries occurred in almost 70% of the patients. The prospective study showed that patients fell mostly at home, mainly due to intrinsic (patient related) causes, and usually in a forward direction. Fallers were unstable while climbing stairs, rising from a chair and standing with eyes closed whereas non-fallers had normal balance control. Frequent fallers had greater muscle weakness than infrequent fallers. CONCLUSION: These findings demonstrate the high prevalence and clinical relevance of falls in FSHD. The relation between muscle weakness and instability among fallers is also highlighted. Because patients fell mainly at home, fall prevention strategies should focus on home adaptations. As mainly intrinsic causes underlie falls, the impact of adopting balance strategies or balance training should be explored in this patient group.
Assuntos
Acidentes por Quedas/estatística & dados numéricos , Distrofia Muscular Facioescapuloumeral/fisiopatologia , Acidentes Domésticos/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Força Muscular/fisiologia , Debilidade Muscular/fisiopatologia , Distrofia Muscular Facioescapuloumeral/complicações , Países Baixos/epidemiologia , Equilíbrio Postural/fisiologia , Prevalência , Estudos Prospectivos , Estudos Retrospectivos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Patients with facioscapulohumeral muscular dystrophy (FSHD) show a contraction of the D4Z4 repeat array in the subtelomere of chromosome 4q. This D4Z4 contraction is associated with significant allele-specific hypomethylation of the repeat. Hypomethylation of D4Z4 is also observed in patients with phenotypic FSHD without contraction of D4Z4 and in patients with the immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome, an unrelated disease that does not present with muscular dystrophy and is in part caused by DNMT3B mutations. METHODS: In order to identify the gene defect and to find the pathogenetic epigenetic pathway in phenotypic FSHD, we have aimed to identify the differences and commonalities in phenotypic FSHD and ICF by 1) investigation of DNA methylation of non-D4Z4 repeat arrays, 2) analysis of mitogen-stimulated lymphocytes to detect pericentromeric abnormalities involving chromosomes 1, 9, and 16, 3) determination of IgA, IgG, and IgM levels, and 4) mutational analysis of candidate genes to identify a second disease locus involved in the pathogenesis of phenotypic FSHD. RESULTS: Our results do not show epigenetic or phenotypic commonalities between phenotypic FSHD and ICF other than the earlier observed D4Z4 hypomethylation. We could not identify any mutations in the candidate genes tested for. CONCLUSION: Our data suggest that in phenotypic FSHD hypomethylation is restricted to D4Z4 and that phenotypic FSHD and ICF do not share a defect in the same molecular pathway.
Assuntos
Cromossomos Humanos Par 4/genética , Metilação de DNA , Distrofia Muscular Facioescapuloumeral/genética , Fenótipo , Sequências de Repetição em Tandem/genética , Adulto , Idoso , Alelos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Distrofia Muscular Facioescapuloumeral/metabolismo , Mutação , LinhagemRESUMO
Pheno- and genotype correlation is attempted in a Dutch cross-sectional study on limb- girdle muscular dystrophy. Sarcoglycans, caveolin-3, calpain-3, and dysferlin were analyzed on muscle tissue. Mutation analysis of the calpain-3, caveolin-3, and fukutin-related protein gene was executed in successive order for all samples. In 51% of all families a classifying diagnosis was made. Several new mutations in LGMD2A, B, and C patients have been found in this population.
Assuntos
Predisposição Genética para Doença/genética , Proteínas Musculares/genética , Músculo Esquelético/metabolismo , Distrofia Muscular do Cíngulo dos Membros/genética , Mutação/genética , Adolescente , Adulto , Calpaína/genética , Caveolina 3/genética , Mapeamento Cromossômico , Estudos Transversais , Análise Mutacional de DNA , Disferlina , Feminino , Testes Genéticos , Genótipo , Humanos , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Músculo Esquelético/fisiopatologia , Países Baixos , Pentosiltransferases , Fenótipo , Proteínas/genéticaRESUMO
BACKGROUND: We recently reported a randomised controlled trial on the efficacy of strength training and the beta2-adrenergic agonist albuterol in patients with facioscapulohumeral muscular dystrophy (FSHD). Strength training and albuterol appeared safe interventions with limited positive effect on muscle strength and volume. We concurrently explored the prevalence and the characteristics of pain and fatigue in the participating FSHD patients, because these are probably underreported but clinically relevant symptoms in this disorder. Next, we studied the effects of albuterol and strength training on pain, experienced fatigue, health-related functional status and psychological distress. METHODS: Sixty-five patients were randomised to strength training of elbow flexors and ankle dorsiflexors or non-training. After 26 weeks, albuterol (sustained-release, 8 mg bid) was added in a randomised, double-blind, placebo-controlled design. Outcomes comprised self-reported pain, experienced fatigue, functional status and psychological distress obtained with validated questionnaires at 52 weeks. RESULTS: Eighty percent of patients reported chronic persistent or periodic, multifocal pains. Thirty-four percent of the participants were severely fatigued. Strength training and albuterol failed to have a significant effect on all outcomes. CONCLUSIONS: Pain and fatigue are important features in FSHD. Strength training and albuterol do not have a positive or negative effect on pain, experienced fatigue, functional status and psychological distress.
Assuntos
Agonistas Adrenérgicos beta/uso terapêutico , Albuterol/uso terapêutico , Exercício Físico , Fadiga/terapia , Manejo da Dor , Adulto , Terapia Combinada , Método Duplo-Cego , Fadiga/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Força Muscular/fisiologia , Distrofia Muscular Facioescapuloumeral/complicações , Distrofia Muscular Facioescapuloumeral/terapia , Dor/etiologia , Medição da Dor/métodos , Aptidão Física , Perfil de Impacto da Doença , Estatísticas não Paramétricas , Fatores de TempoRESUMO
The feasibility of a novel method for the noninvasive and local assessment of creatine (Cr) and phosphocreatine (PCr) dynamics in human skeletal muscle based on (13)C magnetic resonance (MR) spectroscopy is presented. A high dose of Cr, labeled at the guanidino C-4 position with (13)C 11% enrichment, was administered orally to a human subject for 5 days. Using a surface coil, (13)C MR spectra of the lower leg were acquired on a 1.5T MR system at regular time intervals during and after Cr supplementation. An almost twofold increase in the intensities of the resolved PCr and Cr (13)C-4 signals was observed during this period. The slow decrease in these signals to normal values after supplementation reflects the slow daily turnover of Cr. The PCr/Cr ratio did not appear to change over the whole measurement period. During exercise of the leg, reversible changes in PCr and Cr signals were observed, reflecting conversion by the Cr kinase reaction.
Assuntos
Creatina/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Músculo Esquelético/metabolismo , Esforço Físico/fisiologia , Radioisótopos de Carbono/farmacocinética , Humanos , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Fosfocreatina/metabolismoRESUMO
Facioscapulohumeral muscular dystrophy (FSHD) is associated with a contraction of the D4Z4 allele on chromosome 4qter. There is also marked DNA hypomethylation of the D4Z4 allele. The DNA hypomethylation may have a central role in the pathogenesis of FSHD. Supplemental folic acid can boost DNA methylation. We evaluated the effect of oral folic acid and methionine supplementation on the methylation level of 4qter D4Z4 alleles in peripheral-blood lymphocytes of nine patients affected with FSHD and six healthy controls. Methylation levels did not change, while recommended serum-folate concentrations were reached.
Assuntos
Alelos , Metilação de DNA/efeitos dos fármacos , Ácido Fólico/farmacologia , Metionina/farmacologia , Distrofia Muscular Facioescapuloumeral/genética , Adolescente , Adulto , Estudos de Casos e Controles , DNA/genética , Suplementos Nutricionais , Feminino , Ácido Fólico/administração & dosagem , Ácido Fólico/sangue , Humanos , Masculino , Metionina/administração & dosagem , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Distrofia Muscular Facioescapuloumeral/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Projetos PilotoRESUMO
Dysphagia is not considered a symptom of facioscapulohumeral muscular dystrophy (FSHD). In this study, the authors found that dysphagia does occur in patients with advanced FSHD showing mild involvement of the jaw and lingual muscles. Dysphagia is seldom life threatening in these patients. The authors conclude that dysphagia should not be considered an exclusion criterion for FSHD.
Assuntos
Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/etiologia , Distrofia Muscular Facioescapuloumeral/complicações , Distrofia Muscular Facioescapuloumeral/diagnóstico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The objective was to evaluate the applicability and reliability of an unbiased stereological computerised tomography (CT) method for estimating total human body (HB), skeletal muscle (SM) and adipose tissue (AT) volumes in groups of neuromuscular patients. In 10 neuromuscular patients HB, SM and AT volumes were estimated using systematic sampling on equidistant CT sections throughout the total body axis using a counting grid with systematically ordered intersection points. Each intersection point hitting HB, SM or AT represented a known volume dependent on intersection point distance and sum of section thickness and gap. Random and systematic intra- and interobserver errors for volume estimates were below 0.035. These errors were negligible to the coefficient of variation of the group mean, being 0.190 for HB, 0.323 for SM and 0.471 for AT. Even in the presence of intrafascicular and intramuscular fat in neuromuscular patients, unbiased and reliable quantification of HB, SM and AT is possible.
Assuntos
Tecido Adiposo/patologia , Músculo Esquelético/patologia , Doenças Neuromusculares/patologia , Tomógrafos Computadorizados , Adulto , Feminino , Corpo Humano , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To assess the prevalence of severe fatigue and its relation to functional impairment in daily life in patients with relatively common types of neuromuscular disorders. METHODS: 598 patients with a neuromuscular disease were studied (139 with facioscapulohumeral dystrophy, 322 with adult onset myotonic dystrophy, and 137 with hereditary motor and sensory neuropathy type I). Fatigue severity was assessed with Checklist Individual Strength (CIS-fatigue). Functional impairments in daily life were measured with the short form 36 item health questionnaire (SF-36). RESULTS: The three different neuromuscular patient groups were of similar age and sex. Severe experienced fatigue was reported by 61-74% of the patients. Severely fatigued patients had more problems with physical functioning, social functioning, mental health, bodily pain, and general health perception. There were some differences between the three disorders in the effects of fatigue. CONCLUSIONS: Severe fatigue is reported by the majority of patients with relatively common types of neuromuscular disorders. Because experienced fatigue severity is associated with the severity of various functional impairments in daily life, it is a clinically and socially relevant problem in this group of patients.
Assuntos
Doença de Charcot-Marie-Tooth/epidemiologia , Fadiga/epidemiologia , Distrofia Muscular Facioescapuloumeral/epidemiologia , Distrofia Miotônica/epidemiologia , Atividades Cotidianas , Adolescente , Adulto , Idoso , Atitude Frente a Saúde , Doença de Charcot-Marie-Tooth/diagnóstico , Doença de Charcot-Marie-Tooth/fisiopatologia , Fadiga/diagnóstico , Fadiga/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Distrofia Muscular Facioescapuloumeral/diagnóstico , Distrofia Muscular Facioescapuloumeral/fisiopatologia , Distrofia Miotônica/diagnóstico , Distrofia Miotônica/fisiopatologia , Dor/diagnóstico , Dor/epidemiologia , Medição da Dor , Índice de Gravidade de Doença , Comportamento SocialRESUMO
Myositis specific autoantibodies (MSAs) are proven to be specific for myositis compared with other inflammatory connective tissue diseases. Their specificity compared, however, with other neuromuscular disorders, which are included in the differential diagnosis of patients in whom the diagnosis myositis is under consideration, is unknown. We prospectively screened sera from 107 patients with various neuromuscular disorders for the most common MSAs and compared the results with the findings in a group of 97 myositis patients, published previously. Special attention was paid to patients with facioscapulohumeral muscular dystrophy (FSHD), an autosomal dominant muscle disease with marked inflammation in skeletal muscle tissue. Only one patient in the neuromuscular disorders group tested positive for an MSA, compared with 41 in the myositis group, resulting in a specificity of 99%. None of the FSHD patients tested positive. We conclude that the tested MSAs are highly specific for myositis and that they are not merely associated with muscle inflammation.