Respiratory involvement in ambulant and non-ambulant patients with facioscapulohumeral muscular dystrophy

Journal of Neurology - Understand the occurrence and predictors of respiratory impairment in FSHD. Data from 100 FSHD patients was collected regarding demographics, genetics, respiratory status and...     

Restrictive lung involvement in facioscapulohumeral muscular dystrophy

Introduction: Few studies have evaluated the frequency or predisposing factors for respiratory involvement in facioscapulohumeral muscular dystrophy type 1 (FSHD1) and type 2 (FSHD2). Methods: We performed a prospective cross‐sectional observational study of 61 genetically confirmed FSHD participants (53 FSHD1 and 8 FSHD2). Participants underwent bedside pulmonary function testing in sitting and supine positions, a standard clinical history and physical assessment, and manual muscle testing. Results: Restrictive respiratory involvement was suggested in 9.8% (95% confidence interval 2.4–17.3): 7.5% FSHD1 and 25.0% FSHD2 (P = 0.17). Participants with testing suggestive of restrictive lung involvement (n = 6) were more severely affected (P = 0.005), had weaker hip flexion (P = 0.0007), and were more likely to use a wheelchair (P = 0.01). Conclusions: Restrictive respiratory involvement should be considered in all moderate to severely affected FSHD patients with proximal lower extremity weakness. The higher frequency of restrictive lung disease in FSHD2 seen here requires confirmation in a larger cohort of FSHD2 patients. Muscle Nerve 50 : 739–743, 2014     

A scapular onset muscular dystrophy without facial involvement: Possible allelism with facioscapulohumeral muscular dystrophy

A dominantly inherited muscular dystrophy with onset in the shoulder girdle and later progression to the lower limbs is described. The disorder was clinically distinguishable from known facioscapulohumeral, scapulohumeral and limb girdle syndromes. A 38 kb allele detected by probe p13E-11 (D4F104S1) segregated with the disease. Linkage analysis gave a maximum lod score of z = 1.61 at θ = 0.01 with the 4q35 marker D4S184 (affected only analysis z = 1.20 at θ = 0.01) suggesting probable allelism with facioscapulohumeral muscular dystrophy.     

Scapulothoracic arthrodesis for patients with facioscapulohumeral muscular dystrophy

Ten scapulothoracic arthrodesis procedures were performed in six patients with facioscapulohumeral muscular dystrophy in order to improve considerably restricted activities of daily living. Four of these procedures were bilateral. The duration of follow-up ranged from 28 to 120 months. All patients reported improved function in activities of daily living. Active shoulder abduction was improved by an average of 44°, and active flexion increased by 56°. There was no deterioration in improved upper limb function with time. Complications included pneumothorax, atelectasis, pleural effusion and re-exploration for a segment of retained drain.     

Leg muscle involvement in facioscapulohumeral muscular dystrophy assessed by MRI

Using MRI, we evaluated the degree of involvement of muscles in the lower extremities of 18 unselected patients with facioscapulohumeral muscular dystrophy (FSHD). Findings were correlated with fragment size of the mutated gene, age, disease duration and muscle power. Most affected muscles were the hamstrings followed by the tibialis anterior and the medial gastrocnemius. The vastus-, gluteal- and peroneal muscles were the most unaffected, and the psoas muscle did not show evidence of involvement in any of the investigated subjects. Asymmetric involvement was evident in 15% of the investigated muscles on MRI and 6% on manual muscle strength testing. MRI findings in muscle tended to correlate with disease duration (r = 0.49; p < 0.05), but not with gene fragment size or age. MRI disclosed involvement of muscles performing hip flexion and ankle dorsal flexion that could not be detected by manual muscle strength testing. Otherwise, there was a close correlation (≈ r = 0.75; p < 0.0001) between muscle strength and MRI severity score for other muscle groups. The present study shows that MRI may disclose muscle involvement in FSHD that is not apparent on manual muscle testing, and suggests that MRI of muscle may be an important assessment tool in clinical trials involving patients with FSHD. Received in revised form: 10 March 2006     

Dysphagia in facioscapulohumeral muscular dystrophy

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.     

Quantitative MR imaging of individual muscle involvement in facioscapulohumeral muscular dystrophy

The purpose of this study was to implement a quantitative MR imaging method for the determination of muscular and fat content in individual skeletal muscles of patients with facioscapulohumeral muscular dystrophy (FSHD).Turbo Inversion Recovery Magnitude (TIRM) and multiecho MR images were acquired from seven FSHD patients and healthy volunteers. Signal decay in the multiecho MR images was fitted to a biexponential function with fixed relaxation rates for muscle and fat tissue and used to calculate the degree of fatty infiltration in eight muscles in the lower leg.Considerable differences in fatty infiltration between different muscles were observed in FSHD patients, suggesting that this could be used as a biomarker for disease progression. TIRM imaging indicated an inflammatory component of the disease previously only observed in muscle biopsies. Typically, muscle involvement was non-uniform even within one muscle, indicating that MRI can be used as a valuable tool to study pathophysiology and therapy evaluation in FSHD.     

Quality of life and pain in patients with facioscapulohumeral muscular dystrophy

The aim of this study was to assess quality of life (QoL) and evaluate the occurrence and characteristics of pain in facioscapulohumeral muscular dystrophy (FSHD) patients. No study has yet assessed QoL in a large group of FSHD patients and, overall, few studies have assessed pain in neuromuscular diseases. We performed a prospective study using a multidimensional protocol including: clinical (according to the Clinical Severity Scale Rev1); genetic (p13E‐11 EcoRI fragments Rev1); QoL (Short Form‐36); pain (Visual Analog Scale and Portenoy‐6 questions); and depression (Beck Depression Inventory) assessment. QoL measures of FSHD were compared with those of Italian norms. Moreover, we correlated QoL and pain measurements with clinical findings. Sixty‐five patients were enrolled in the study. QoL was statistically significantly reduced with respect to the Italian normative sample, mainly in physical domains. Our study demonstrated that pain is frequent in FSHD patients. More than half of the patients complained of at least moderate pain. Women complained of slightly higher levels of deterioration in the emotional aspects of QoL than men. Clinical pattern (as assessed by Clinical Severity Scale) was closely related to physical QoL domains: the higher the clinical involvement, the more severe the QoL deterioration. This study provided information that may be crucial in clinical practice: pain may be a relevant aspect in FSHD patients, and prevention strategies or relevant therapies should be considered as appropriate. Moreover, we must pay more attention to gender differences: women can suffer far greater deterioration in the emotional aspects of QoL. Further multidimensional observations are needed. Muscle Nerve 40: 200–205, 2009     

Inflammatory changes in facioscapulohumeral muscular dystrophy

Summary Fifteen patients (10 familial and 5 sporadic cases) with facioscapulohumeral dystrophy were studied with regard to the presence of inflammatory changes. Mononuclear infiltrations were not characteristic of any stage of the disease, but they may be present in differring degrees during the whole course of the process. However, their lack or presence was uniform in the affected families, suggesting that the appearance of infiltrations may be genetically determined. Parallel with the presence of cell infiltrations, the serum creatine kinase (CK) activity was moderately increased and the progress of the disease was slightly accelerated. The relation of these phenomena to polymyositis and the diagnostic difficulties are discussed.     

Tongue atrophy in facioscapulohumeral muscular dystrophy

Involvement of the lingual muscle is considered one of the exclusion criteria of facioscapulohumeral muscular dystrophy (FSHD). In a series of 151 Japanese patients with 4q35-FSHD, seven patients (4.6%) had tongue atrophy with abnormal MRI findings and typical myogenic patterns of electromyography. All seven patients belong to a group of early-onset FSHD with large gene deletions on chromosome 4q35. Our result suggests that the patients with 4q35-FSHD could have myopathic tongue atrophy.     

Diagnostic challenges in facioscapulohumeral muscular dystrophy

The diagnosis of facioscapulohumeral muscular dystrophy (FSHD) can be difficult due to its clinical variability and complex genetic cause. We present three challenging cases: one misdiagnosis of FSHD, one patient with FSHD resembling mitochondrial myopathy, and one patient with combined FSHD and limb girdle muscular dystrophy 2A. Detailed clinical and genetic evaluation, including 4qA/4qB allele determination, may be needed for the diagnosis of FSHD.     

Ventilatory support in facioscapulohumeral muscular dystrophy

Respiratory insufficiency due to respiratory muscle weakness is a common complication of many neuromuscular diseases. The prevalence of respiratory failure in facioscapulohumeral muscular dystrophy (FSHD) is unknown. The authors identified 10 FSHD patients on nocturnal ventilatory support at home, representing approximately 1% of the Dutch FSHD population. Severe muscle disease, wheelchair dependency, and kyphoscoliosis appeared to be risk factors for respiratory failure.     

Linkage studies in facioscapulohumeral muscular dystrophy

Possible linkage between the locus for autosomal dominant facioscapulo-humeral muscular dystrophy and the locus for the constant region of the heavy chains of the IgG immunoglobulins (Gm) was tested in 1 kindred (23 affected and 18 unaffected sibs) using the polymorphic DNA probe D14S1, which is known to be closely linked with Gm. No linkage between the loci for the disease and the probe was found, and the lod scores suggested that the locus for facioscapulohumeral muscular dystrophy is not situated on the distal part of the long arm of chromosome 14.     

Sarcolemmal reorganization in facioscapulohumeral muscular dystrophy

OBJECTIVE: We examined the sarcolemma of skeletal muscle from patients with facioscapulohumeral muscular dystrophy (FSHD1A) to learn if, as in other murine and human muscular dystrophies, its organization and relationship to nearby contractile structures are altered. METHODS: Unfixed biopsies of control and FSHD deltoid and biceps muscles, snap-frozen at resting length, were cryosectioned, indirectly immunolabeled with fluorescent antibodies to sarcolemmal and myofibrillar markers, and examined with confocal microscopy to localize the immunolabeled proteins. Glutaraldehyde-fixed samples were stained with heavy metals, embedded, thin-sectioned, and examined with electron microscopy to determine the relationship between the sarcolemma and the underlying myofibrils. RESULTS: Confocal microscopy showed that some of the structures at the sarcolemma in FSHD samples were misaligned with respect to the underlying contractile apparatus. Electron microscopy showed a significant increase in the distance between the sarcolemma and the nearest myofibrils, from less than 100 nm in controls to values as high as 550 nm in FSHD. INTERPRETATION: Our results show that the pathophysiology of FSHD includes novel changes in the organization of the sarcolemma and its association with nearby contractile structures and suggest that, as in other muscular dystrophies, the integrity of the sarcolemma may be compromised in FSHD.