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The 4-point Heckmatt grading scale can easily be used to analyze muscle ultrasound images. The scale is used in an expanding set of muscles and neuromuscular disorders. This prompted the need for evaluation of the measurement properties of the scale in its current form. In this retrospective observational study we included muscle ultrasound images from patients who were undergoing an ultrasound exam for either clinical or research purposes. The primary outcome of this study was to investigate and improve the measurement properties of the Heckmatt scale using Rasch analysis. We investigated whether observers consistently used the 4 response categories. Data was available of 30.967 muscle ultrasound images from 1783 patients and 43 different individual muscles. In 8 of the 43 muscles, observers had difficulty to discriminate between the response categories, especially in bulbar muscles. After rescoring to a 3-point scale, the response categories were consistently used in all 43 muscles. In conclusion, a 3-point Heckmatt grading scale leads to improved accurate scoring compared to the original 4-point Heckmatt grading scale. Using the 3-point Heckmatt grading scale will not only simplify the use of the scale but also enhance its application in clinical practice and research purposes.
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OBJECTIVES: Muscle MRI and ultrasound provide complementary techniques for characterizing muscle changes and tracking disease progression in facioscapulohumeral muscular dystrophy (FSHD). In this cohort study, we provide longitudinal data that compares both imaging modalities head-to-head. METHODS: FSHD patients were assessed at baseline and after five years. Standardized muscle MRI and ultrasound images of five leg muscles were assessed bilaterally. Fat replacement was quantified using MRI fat-fraction (FF) and ultrasound Heckmatt and echogenicity z-scores (EZ-score). Muscle edema was evaluated using T2-weighted turbo inversion recovery magnitude (TIRM) MRI. RESULTS: Twenty FSHD patients were included. Muscles with normal baseline imaging showed increases in ultrasound EZ-scores (≥1; in 17%) more often than MRI FF increases (≥10%; in 7%) over time. Muscles with only baseline ultrasound abnormalities often showed considerable FF increases (in 22%), and TIRM positivity at follow-up (44%). Muscles with increased FF at baseline showed stable (80%) or increasing FF (20%) over time. EZ-scores of those muscles either increased (23%), decreased (33%) or remained stable (44%). CONCLUSIONS: Muscle ultrasound may capture accelerated pathological muscle changes in FSHD in early disease, while muscle MRI appears better-suited to detecting and monitoring pathology in later stages. SIGNIFICANCE: Our results help establish each techniques' optimal use as imaging biomarker.
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Background: Facial weakness is a key feature of facioscapulohumeral muscular dystrophy (FSHD) and may lead to altered facial expression and subsequent psychosocial impairment. There is no cure and supportive treatments focus on optimizing physical fitness and compensation of functional disabilities. Objective: We hypothesize that symptomatic treatment options and psychosocial interventions for other neurological diseases with altered facial expression could be applicable to FSHD. Therefore, the aim of this review is to collect symptomatic treatment approaches that target facial muscle function and psychosocial interventions in various neurological diseases with altered facial expression in order to discuss the applicability to FSHD. Methods: A systematic search was performed. Selected studies had to include FSHD, Bell's palsy, Moebius syndrome, myotonic dystrophy type 1, or Parkinson's disease and treatment options which target altered facial expression. Data was extracted for study and patients' characteristics, outcome assessment tools, treatment, outcome of facial expression and or psychosocial functioning. Results: Forty studies met the inclusion criteria, of which only three studies included FSHD patients exclusively. Most, twenty-one, studies were performed in patients with Bell's palsy. Studies included twelve different therapy categories and results were assessed with different outcomes measures. Conclusions: Five therapy categories were considered applicable to FSHD: training of (non-verbal) communication compensation strategies, speech training, physical therapy, conference attendance, and smile restoration surgery. Further research is needed to establish the effect of these therapies in FSHD. We recommend to include outcome measures in these studies that cover at least cosmetic, functional, communication, and quality of life domains.
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Expresión Facial , Distrofia Muscular Facioescapulohumeral , Distrofia Muscular Facioescapulohumeral/terapia , Humanos , Músculos Faciales/fisiopatología , Parálisis de Bell/terapiaRESUMEN
Background: FSHD is a highly prevalent inherited myopathy with a still poorly understood pathology. Objective: To investigate whether proinflammatory cytokines are associated with FSHD and which specific innate immune cells are involved in its pathology. Methods: First, we measured circulating cytokines in serum samples: IL-6 (FSHD, nâ=â150; HC, nâ=â98); TNF (FSHD, nâ=â150; HC, nâ=â59); IL-1α (FSHD, nâ=â150; HC, nâ=â66); IL-1ß (FSHD, nâ=â150; HC, nâ=â98); MCP-1 (FSHD, nâ=â14; HC, nâ=â14); VEGF-A (FSHD, nâ=â14; HC, nâ=â14). Second, we tested trained immunity in monocytes (FSHD, nâ=â15; HC, nâ=â15) and NK cells (FSHD, nâ=â11; HC, nâ=â11). Next, we explored the cytokine production capacity of NK cells in response to different stimuli (FSHD, nâ=â39; HC, nâ=â22). Lastly, we evaluated the cytokine production of ex vivo stimulated MRI guided inflamed (TIRM+) and paired MRI guided non inflamed (TIRM-) muscle biopsies of 21 patients and of 8 HC muscle biopsies. Results: We included a total of 190 FSHD patients (Nâ=â190, 48±14 years, 49% men) and of 135 HC (Nâ=â135, 44±15 years, 47% men). We found that FSHD patients had higher concentrations of IL-6 and TNF measured (a) in the circulation, (b) after ex-vivo stimulation of NK cells, and (c) in muscle specimens. Besides, IL-6 circulating concentrations, as well as its production by NK cells and IL-6 content of FSHD muscle specimens, showed a mild correlation with disease duration, disease severity, and muscle weakness. Conclusion: These results show that IL-6 and TNF may contribute to FSHD pathology and suggest novel therapeutic targets. Additionally, the activation of NK cells in FSHD may be a novel pathway contributing to FSHD pathology.
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Distrofia Muscular Facioescapulohumeral , Femenino , Humanos , Masculino , Biomarcadores , Biopsia , Interleucina-6 , Debilidad Muscular , Distrofia Muscular Facioescapulohumeral/patologíaRESUMEN
PURPOSE: To perform a scoping review to investigate the psychosocial impact of having an altered facial expression in five neurological diseases. METHODS: A systematic literature search was performed. Studies were on Bell's palsy, facioscapulohumeral muscular dystrophy (FSHD), Moebius syndrome, myotonic dystrophy type 1, or Parkinson's disease patients; had a focus on altered facial expression; and had any form of psychosocial outcome measure. Data extraction focused on psychosocial outcomes. RESULTS: Bell's palsy, myotonic dystrophy type 1, and Parkinson's disease patients more often experienced some degree of psychosocial distress than healthy controls. In FSHD, facial weakness negatively influenced communication and was experienced as a burden. The psychosocial distress applied especially to women (Bell's palsy and Parkinson's disease), and patients with more severely altered facial expression (Bell's palsy), but not for Moebius syndrome patients. Furthermore, Parkinson's disease patients with more pronounced hypomimia were perceived more negatively by observers. Various strategies were reported to compensate for altered facial expression. CONCLUSIONS: This review showed that patients with altered facial expression in four of five included neurological diseases had reduced psychosocial functioning. Future research recommendations include studies on observers' judgements of patients during social interactions and on the effectiveness of compensation strategies in enhancing psychosocial functioning.
Negative effects of altered facial expression on psychosocial functioning are common and more abundant in women and in more severely affected patients with various neurological disorders.Health care professionals should be alert to psychosocial distress in patients with altered facial expression.Learning of compensatory strategies could be a beneficial therapy for patients with psychosocial distress due to an altered facial expression.
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Facioscapulohumeral muscular dystrophy (FSHD) is a slowly progressive disease of skeletal muscle. Dual energy X-ray absorptiometry (DEXA) is a widely available, cost-effective and sensitive technique for measuring whole body and regional lean tissue mass and has been used in prior clinical trials in neuromuscular diseases. The Clinical Trial Readiness to Solve Barriers to Drug Development in FSHD (ReSolve) study is a prospective, longitudinal, observational multisite study. We obtained concurrent DEXA scans and functional outcome measurements in 185 patients with FSHD at the baseline visit. We determined the associations between lean tissue mass in the upper and lower extremities and corresponding clinical outcome measures. There were moderate correlations between upper and lower extremity lean tissue mass and their corresponding strengths and function. Lean tissue mass obtained by DEXA scan may be useful as a biomarker in future clinical trials in FSHD.
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Distrofia Muscular Facioescapulohumeral , Humanos , Distrofia Muscular Facioescapulohumeral/diagnóstico por imagen , Absorciometría de Fotón/métodos , Estudios Prospectivos , Músculo Esquelético , Evaluación de Resultado en la Atención de SaludRESUMEN
BACKGROUND: It is unclear how changes in quantitative muscle magnetic resonance imaging (MRI) relate to changes in clinical outcome in facioscapulohumeral muscular dystrophy (FSHD), although this information is crucial for optimal use of MRI as imaging biomarker in trials. We therefore assessed muscle MRI and clinical outcome measures in a large longitudinal prospective cohort study. METHODS: All patients were assessed by MRI at baseline and at 5-year follow-up, employing 2pt-Dixon and turbo inversion recovery magnitude (TIRM) sequences, after which fat fraction and TIRM positivity of 19 leg muscles were determined bilaterally. The MRI compound score (CoS) was defined as the mean fat fraction of all muscles weighted for cross-sectional area. Clinical outcome measures included the Ricci-score, FSHD clinical score (FSHD-CS), MRC sumscore (MRC-SS), and motor-function-measure (MFM). RESULTS: We included 105 FSHD patients [mean age 54 ± 14 years, median Ricci-score 7 (range 0-10)]. The median change over 5 years' time in the MRI-CoS was 2.0% (range -4.6 to +12.1; P < 0.001). The median change over 5 years' time in clinical outcome measures was small in all measures, with z-scores ranging from 5.0 to 7.2 (P < 0.001). The change in MRI-CoS correlated with change in FSHD-CS and Ricci-score (ρ = 0.25, respectively; ρ = 0.23, P < 0.05). The largest median increase in MRI-CoS was seen in baseline subgroups with an MRI-CoS 20-40% (6.1%), with ≥2 TIRM positive muscles (3.5%) or with an FSHD-CS 5-10 (3.1%). CONCLUSIONS: This 5-year study showed significant changes in MRI and clinical outcome measures and a significant correlation between changes in MRI-CoS and changes in clinical outcome measures. In addition, we identified subgroups of patients that are most prone to radiological disease progression. This knowledge further establishes quantitative MRI parameters as prognostic biomarkers in FSHD and as efficacy biomarkers in upcoming clinical trials.
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Distrofia Muscular Facioescapulohumeral , Humanos , Adulto , Persona de Mediana Edad , Anciano , Distrofia Muscular Facioescapulohumeral/diagnóstico por imagen , Estudios de Seguimiento , Estudios Prospectivos , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/patología , Imagen por Resonancia Magnética/métodos , BiomarcadoresRESUMEN
Muscle biopsies are used in clinical trials to measure target engagement of the investigational product. With many upcoming therapies for patients with facioscapulohumeral dystrophy (FSHD), the frequency of biopsies in FSHD patients is expected to increase. Muscle biopsies were performed either in the outpatient clinic using a Bergström needle (BN-biopsy) or in a Magnetic Resonance Imaging machine (MRI-biopsy). This study assessed the FSHD patients' experience of biopsies using a customized questionnaire. The questionnaire was sent to all FSHD patients who had undergone a needle muscle biopsy for research purposes, inquiring about biopsy characteristics and burden, and willingness to undergo a subsequent biopsy. Forty-nine of 56 invited patients (88%) completed the questionnaire, reporting on 91 biopsies. The median pain score (scale 0-10) during the procedure was 5 [2-8], reducing to 3 [1-5] and 2 [1-3] after one and 24 h, respectively. Twelve biopsies (13.2%) resulted in complications, eleven resolved within 30 days. BN-biopsies were less painful compared to MRI-biopsies (median NRS: 4 [2-6] vs. 7 [3-9], p = 0.001). The burden of needle muscle biopsies in a research setting is considerate and should not be underestimated. MRI-biopsies have a higher burden compared to BN-biopsies.
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Distrofia Muscular Facioescapulohumeral , Humanos , Distrofia Muscular Facioescapulohumeral/diagnóstico por imagen , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/patología , Biopsia , Imagen por Resonancia Magnética/métodos , Instituciones de Atención AmbulatoriaAsunto(s)
Distrofia Muscular Facioescapulohumeral , Humanos , Distrofia Muscular Facioescapulohumeral/diagnóstico , Distrofia Muscular Facioescapulohumeral/genética , Distrofia Muscular Facioescapulohumeral/terapia , Biomarcadores , Progresión de la Enfermedad , Evaluación de Resultado en la Atención de SaludRESUMEN
Advances in the molecular understanding of facioscapulohumeral muscular dystrophy (FSHD) have revealed that FSHD results from epigenetic de-repression of the DUX4 gene in skeletal muscle, which encodes a transcription factor that is active in early embryonic development but is normally silenced in almost all somatic tissues. These advances also led to the identification of targets for disease-altering therapies for FSHD, as well as an improved understanding of the molecular mechanism of the disease and factors that influence its progression. Together, these developments led the FSHD research community to shift its focus towards the development of disease-modifying treatments for FSHD. This Review presents advances in the molecular and clinical understanding of FSHD, discusses the potential targeted therapies that are currently being explored, some of which are already in clinical trials, and describes progress in the development of FSHD-specific outcome measures and assessment tools for use in future clinical trials.
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Distrofia Muscular Facioescapulohumeral , Humanos , Distrofia Muscular Facioescapulohumeral/genética , Distrofia Muscular Facioescapulohumeral/terapia , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Músculo Esquelético/metabolismo , Regulación de la Expresión GénicaRESUMEN
PURPOSE: Facial weakness and its functional consequences are an often underappreciated clinical feature of facioscapulohumeral muscular dystrophy (FSHD) by healthcare professionals and researchers. This is at least in part due to the fact that there are few adequate clinical outcome measures available. METHODS: We developed the Facial Function Scale, a Rasch-built questionnaire on the functional disabilities relating to facial weakness in FSHD. A preliminary 33-item questionnaire was created based on semi-structured interviews with 16 FSHD patients and completed by 119 patients. For reliability studies, 73 patients completed it again after a two-week interval. Data were subjected to semi-automated Rasch analysis to select the most appropriate item set to fit model expectations. RESULTS: This resulted in a 25-item unidimensional, linear-weighted questionnaire with high internal consistency (person separation index = 0.92) and test-retest reliability (patients' locations ICC = 0.98 and items' locations ICC = 0.99). Good external construct validity scores were obtained through correlation with the Communicative Participation Item Bank questionnaire, examiner-reported Facial Weakness Score and facial weakness subscale of the FSHD evaluation score (respectively r = 0.733, r = -0.566, and r = 0.441, all p < 0.001). CONCLUSIONS: This study provides a linear-weighted, clinimetrically sound, patient-reported outcome measure on the functional disabilities relating to facial weakness in FSHD, to enable further research on this relevant topic.Implications for rehabilitationFacial weakness and its functional consequences are an often underappreciated clinical feature of facioscapulohumeral muscular dystrophy (FSHD), both in symptomatic treatment and in research.To enable the development and testing of therapeutic symptomatic interventions for facial weakness, clinical outcome measures are required.This study provides a linear-weighted, clinimetrically sound, patient-reported outcome measure on the functional disabilities relating to facial weakness in FSHD patients.
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Distrofia Muscular Facioescapulohumeral , Humanos , Distrofia Muscular Facioescapulohumeral/diagnóstico , Reproducibilidad de los Resultados , Cara , Comunicación , Medición de Resultados Informados por el PacienteRESUMEN
Rasch analysis is a procedure to develop and validate instruments that aim to measure a person's traits. However, manual Rasch analysis is a complex and time-consuming task, even more so when the possibility of differential item functioning (DIF) is taken into consideration. Furthermore, manual Rasch analysis by construction relies on a modeler's subjective choices. As an alternative approach, we introduce a semi-automated procedure that is based on the optimization of a new criterion, called in-plus-out-of-questionnaire log likelihood with differential item functioning (IPOQ-LL-DIF), which extends our previous criterion. We illustrate our procedure on artificially generated data as well as on several real-world datasets containing potential DIF items. On these real-world datasets, our procedure found instruments with similar clinimetric properties as those suggested by experts through manual analyses.
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Psicometría , Humanos , Psicometría/métodos , Encuestas y Cuestionarios , Probabilidad , Reproducibilidad de los ResultadosRESUMEN
PURPOSE OF REVIEW: This article reviews the current knowledge on the clinical characteristics and disease mechanism of facioscapulohumeral muscular dystrophy (FSHD), as well as advances in targeted therapy development. RECENT FINDINGS: FSHD has a wide range of severity, yet a distinct phenotype characterized by weakness of the facial, shoulder, and upper arm muscles, followed by weakness of the trunk and leg muscles. It can be caused by two genetic mechanisms that share a common downstream pathway, namely, the epigenetic derepression and subsequent misexpression of the myotoxic DUX4 transcription factor. Treatment is currently supportive and outlined in evidence-based guidelines. Advances in the understanding of the pathogenic mechanism of FSHD are paving the way for targeted therapy development. Approaches for targeted therapies to reduce DUX4 expression that are currently being explored include small molecules, antisense oligonucleotides, vector-based RNA interference, and gene therapy. In anticipation of more clinical trials, "clinical trial preparedness," including the development of sensitive biomarkers and clinical outcome measures, are needed. SUMMARY: The cornerstones of the diagnosis of FSHD are clinical observation and genetic testing. Management is currently supportive, but progress in the understanding of the disease mechanism has shifted the field of FSHD toward targeted therapy development.
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Distrofia Muscular Facioescapulohumeral , Humanos , Distrofia Muscular Facioescapulohumeral/diagnóstico , Distrofia Muscular Facioescapulohumeral/genética , Distrofia Muscular Facioescapulohumeral/terapia , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Fenotipo , Biomarcadores/metabolismoRESUMEN
OBJECTIVE: To evaluate the 5-year change in respiratory function in patients with facioscapulohumeral muscular dystrophy (FSHD). METHODS: Genetically confirmed patients with FSHD aged ≥ 18 years were examined twice over five years. Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were measured using hand-held spirometry with a face mask. Several clinical outcome measures were correlated to respiratory function. RESULTS: Ninety-two patients were included (57% male, age 18-75 years). At baseline, the spirometry outcomes of 41 patients showed a restrictive ventilatory pattern (FVC < 80% and FEV1/FVC ≥ 70% of predicted) and of 48 patients at follow-up. The mean FVC decreased from baseline to follow-up from 79.0 to 76.7% predicted (p = 0.021). This decrease was driven by a subgroup of 15 patients who had a deterioration of FVC of > 10% predicted. The subgroup of 15 patients was more severely affected at baseline (p = 0.002 for FSHD clinical score and 0.007 for Ricci score). They developed more frequently spinal and thorax deformities (p < 0.001 for kyphoscoliosis and 0.012 for pectus excavatum) and had a larger decline in axial muscle function (p = 0.020). Only weak correlations were found between the change in FVC% predicted and the change in clinical scores between baseline and follow-up. INTERPRETATION: Respiratory function remained stable in most patients with FSHD, but a subgroup of patients showed a pronounced deterioration. They showed more severe muscle weakness including the leg muscles at baseline (Ricci score ≥ 6), had spinal and thorax deformities and a relatively fast decline in axial muscle function at follow-up.
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Enfermedades Musculares , Distrofia Muscular Facioescapulohumeral , Adolescente , Adulto , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Distrofia Muscular Facioescapulohumeral/complicaciones , Distrofia Muscular Facioescapulohumeral/diagnóstico , Pruebas de Función Respiratoria , Espirometría , Capacidad Vital/fisiologíaRESUMEN
Facioscapulohumeral muscular dystrophy (FSHD) is the second most common genetic myopathy, characterized by slowly progressing and highly heterogeneous muscle wasting with a typical onset in the late teens/early adulthood [1]. Although the etiology of the disease for both FSHD type 1 and type 2 has been attributed to gain-of-toxic function stemming from aberrant DUX4 expression, the exact pathogenic mechanisms involved in muscle wasting have yet to be elucidated [2-4]. The 2021 FSHD International Research Congress, held virtually on June 24-25, convened over 350 researchers and clinicians to share the most recent advances in the understanding of the disease mechanism, discuss the proliferation of interventional strategies and refinement of clinical outcome measures, including results from the ReDUX4 trial, a phase 2b clinical trial of losmapimod in FSHD [NCT04003974].
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Distrofia Muscular Facioescapulohumeral , Adolescente , Adulto , Proteínas de Homeodominio/genética , Humanos , Músculo Esquelético/metabolismo , Atrofia Muscular/metabolismo , Distrofia Muscular Facioescapulohumeral/metabolismoRESUMEN
With several therapeutic strategies for facioscapulohumeral muscular dystrophy (FSHD) entering clinical testing, outcome measures are becoming increasingly important. Considering the spatiotemporal nature of FSHD disease activity, clinical trials would benefit from non-invasive imaging-based biomarkers that can predict FSHD-associated transcriptome changes. This study investigated two FSHD-associated transcriptome signatures (DUX4 and PAX7 signatures) in FSHD skeletal muscle biopsies, and tested their correlation with a variety of disease-associated factors, including Ricci clinical severity score, disease duration, D4Z4 repeat size, muscle pathology scorings and functional outcome measures. It establishes that DUX4 and PAX7 signatures both show a sporadic expression pattern in FSHD-affected biopsies, possibly marking different stages of disease. This study analyzed two imaging-based biomarkers-Turbo Inversion Recovery Magnitude (TIRM) hyperintensity and fat fraction-and provides insights into their predictive power as non-invasive biomarkers for FSHD signature detection in clinical trials. Further insights in the heterogeneity of-and correlation between-imaging biomarkers and molecular biomarkers, as provided in this study, will provide important guidance to clinical trial design in FSHD. Finally, this study investigated the role of infiltrating non-muscle cell types in FSHD signature expression and detected potential distinct roles for two fibro-adipogenic progenitor subtypes in FSHD.
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Proteínas de Homeodominio/genética , Músculo Esquelético/metabolismo , Distrofia Muscular Facioescapulohumeral/genética , Factor de Transcripción PAX7/genética , Transcriptoma , Biomarcadores/metabolismo , Biopsia , Estudios de Casos y Controles , Femenino , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Proteínas de Homeodominio/metabolismo , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/patología , Distrofia Muscular Facioescapulohumeral/diagnóstico por imagen , Distrofia Muscular Facioescapulohumeral/metabolismo , Distrofia Muscular Facioescapulohumeral/patología , Factor de Transcripción PAX7/metabolismo , Índice de Severidad de la Enfermedad , Células Madre/metabolismo , Células Madre/patologíaRESUMEN
INTRODUCTION/AIMS: Neurogenic thoracic outlet syndrome (NTOS) is a heterogeneous and often disputed entity. An electrodiagnostic pattern of T1 > C8 axon involvement is considered characteristic for the diagnosis of NTOS. However, since the advent of high-resolution nerve ultrasound (US) imaging, we have encountered several patients with a proven entrapment of the lower brachial plexus who showed a different, variable electrodiagnostic pattern. METHODS: In this retrospective case series, 14 patients with an NTOS diagnosis with a verified source of compression of the lower brachial plexus and abnormal findings on their electrodiagnostic testing were included. Their medical records were reviewed to obtain clinical, imaging, and electrodiagnostic data. RESULTS: Seven patients showed results consistent with the "classic" T1 axon > C8 pattern of involvement. Less typical findings included equally severe involvement of T1 and C8 axons, more severe C8 involvement, pure motor abnormalities, neurogenic changes on needle electromyography in the flexor carpi radialis and biceps brachii muscles, and one patient with an abnormal sensory nerve action potential (SNAP) amplitude for the median sensory response recorded from the third digit. Patients with atypical findings on electrodiagnostic testing underwent nerve imaging more often compared to patients with classic findings (seven of seven patients vs. five of seven respectively), especially nerve ultrasound. DISCUSSION: When there is a clinical suspicion of NTOS, an electrodiagnostic finding other than the classic T1 > C8 pattern of involvement does not rule out the diagnosis. High resolution nerve imaging is valuable to diagnose additional patients with this treatable condition.
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Electromiografía , Síndrome del Desfiladero Torácico , Plexo Braquial/fisiología , Humanos , Reproducibilidad de los Resultados , Estudios Retrospectivos , Síndrome del Desfiladero Torácico/diagnóstico , Síndrome del Desfiladero Torácico/fisiopatologíaRESUMEN
Reproductive counseling in facioscapulohumeral muscular dystrophy (FSHD) can be challenging due to the complexity of its underlying genetic mechanisms and due to incomplete penetrance of the disease. Full understanding of the genetic causes and potential inheritance patterns of both distinct FSHD types is essential: FSHD1 is an autosomal dominantly inherited repeat disorder, whereas FSHD2 is a digenic disorder. This has become even more relevant now that prenatal diagnosis and preimplantation genetic diagnosis options are available for FSHD1. Pregnancy and delivery outcomes in FSHD are usually favorable, but clinicians should be aware of the risks. We aim to provide clinicians with case-based strategies for reproductive counseling in FSHD, as well as recommendations for pregnancy and delivery.
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Estudios de Asociación Genética , Asesoramiento Genético , Predisposición Genética a la Enfermedad , Distrofia Muscular Facioescapulohumeral/diagnóstico , Distrofia Muscular Facioescapulohumeral/genética , Adulto , Toma de Decisiones Clínicas , Diagnóstico Diferencial , Manejo de la Enfermedad , Femenino , Estudios de Asociación Genética/métodos , Pruebas Genéticas , Humanos , Masculino , Herencia Multifactorial , Fenotipo , Embarazo , Complicaciones del Embarazo , Resultado del Embarazo , Diagnóstico Prenatal , Índice de Severidad de la EnfermedadRESUMEN
PURPOSE: This study focuses on the functional and psychosocial consequences of facial weakness of patients with facioscapulohumeral muscular dystrophy (FSHD) and how they manage their daily lives. MATERIALS AND METHODS: We conducted a qualitative study. Sixteen FSHD patients with varying degrees of facial weakness were interviewed using a semi-structured interview guide. Data were analyzed using the constant comparison approach based on the Straussian Grounded Theory. RESULTS: Reduced facial expression affected different aspects of a participant's life, which is reinforced by fatigue. Particularly the younger participants described the confrontation with reduced facial expression as upsetting. The unpredictability of the progression of facial weakness makes many participants insecure and concerned. They generally tend to avoid discussing facial weakness with loved ones as well as with strangers. CONCLUSIONS: Patients would like the expert teams to shed more light on effective skill training and psychosocial support, especially for the younger patient group. A multidisciplinary approach is needed in addition to programs focusing on the individual aspects of facial weakness. As the experienced psychosocial effect is not commonly equal to the objective degree of facial weakness, we recommend a tailored approach. Finally, these programs should point out the importance of the patient's own ingenuity.Implications for RehabilitationFacial weakness affects both activities and social participation in patients with facioscapulohumeral muscular dystrophy (FSHD), which is reinforced by fatigue.Many participants try to stay down to earth and focus on their ability to self-manage their obstacles regarding facial weakness.Thus, future treatment programs should have a multidisciplinary approach and should point out the importance of the patient's own ingenuity.
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Distrofia Muscular Facioescapulohumeral , Humanos , Distrofia Muscular Facioescapulohumeral/complicaciones , Investigación Cualitativa , Fatiga/etiologíaRESUMEN
Despite the growing knowledge on the (epi)genetic background of facioscapulohumeral muscular dystrophy (FSHD), the substantial variability in disease severity that exists between FSHD patients is not fully understood. We hypothesized that smoking and alcohol consumption are disease modifiers in FSHD and contribute to the variability in disease severity, because they are both associated with higher levels of oxidative stress in muscle tissue. Oxidative stress is known to influence FSHD muscle tissue. One hundred and ninety-eight genetically confirmed FSHD patients completed a questionnaire from which the number of packyears of smoking and the lifetime cumulative alcohol units consumed were calculated. Disease severity was determined by the FSDH evaluation score. Multiple linear regression analyses showed that both the number of packyears and the amount of alcohol consumption did not influence disease severity (respectively Bâ¯=â¯0.025, ΔR2=0.006, pâ¯=â¯0.231; and Bâ¯=â¯0.000, ΔR2=0.004, pâ¯=â¯0.406). Although smoking and excessive alcohol consumption are unhealthy habits which should be discouraged, these results show that smoking and alcohol consumption have no clinically meaningful modifying effect on disease severity in FSHD patients. However, prospective data should show whether alcohol consumption and smoking influence disease progression rate.