Carlier, Robert Y* Dotaz Zobrazit nápovědu
BACKGROUND: Limb girdle muscular dystrophy type R1/2A (LGMDR1/LGMD2A) is a progressive myopathy caused by deficiency of calpain 3, a calcium-dependent cysteine protease of skeletal muscle, and it represents the most frequent type of LGMD worldwide. In the last few years, muscle magnetic resonance imaging (MRI) has been proposed as a tool for identifying patterns of muscular involvement in genetic disorders and as a biomarker of disease progression in muscle diseases. In this study, 57 molecularly confirmed LGMDR1 patients from a European cohort (age range 7-78 years) underwent muscle MRI and a global evaluation of functional status (Gardner-Medwin and Walton score and ability to raise the arms). RESULTS: We confirmed a specific pattern of fatty substitution involving predominantly the hip adductors and hamstrings in lower limbs. Spine extensors were more severely affected than spine rotators, in agreement with higher incidence of lordosis than scoliosis in LGMDR1. Hierarchical clustering of lower limb MRI scores showed that involvement of anterior thigh muscles discriminates between classes of disease progression. Severity of muscle fatty substitution was significantly correlated with CAPN3 mutations: in particular, patients with no or one "null" alleles showed a milder involvement, compared to patients with two null alleles (i.e., predicting absence of calpain-3 protein). Expectedly, fat infiltration scores strongly correlated with functional measures. The "pseudocollagen" sign (central areas of sparing in some muscle) was associated with longer and more severe disease course. CONCLUSIONS: We conclude that skeletal muscle MRI represents a useful tool in the diagnostic workup and clinical management of LGMDR1.
- MeSH
- dítě MeSH
- dospělí MeSH
- kosterní svaly diagnostické zobrazování patologie patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie * MeSH
- mladiství MeSH
- mladý dospělý MeSH
- pletencové svalové dystrofie diagnostické zobrazování genetika patologie patofyziologie MeSH
- senioři MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa MeSH
BACKGROUND: LAMA2-related muscular dystrophy (LAMA2-RD) encompasses a group of recessive muscular dystrophies caused by mutations in the LAMA2 gene, which codes for the alpha-2 chain of laminin-211 (merosin). Diagnosis is straightforward in the classic congenital presentation with no ambulation and complete merosin deficiency in muscle biopsy, but is far more difficult in milder ambulant individuals with partial merosin deficiency. OBJECTIVE: To investigate the diagnostic utility of muscle imaging in LAMA2-RD using whole-body magnetic resonance imaging (WBMRI). RESULTS: 27 patients (2-62 years, 21-80% with acquisition of walking ability and 6 never ambulant) were included in an international collaborative study. All carried two pathogenic mutations, mostly private missense changes. An intronic variant (c.909 + 7A > G) was identified in all the Chilean cases. Three patients (two ambulant) showed intellectual disability, epilepsy, and brain structural abnormalities. WBMRI T1w sequences or T2 fat-saturated images (Dixon) revealed abnormal muscle fat replacement predominantly in subscapularis, lumbar paraspinals, gluteus minimus and medius, posterior thigh (adductor magnus, biceps femoris, hamstrings) and soleus. This involvement pattern was consistent for both ambulant and non-ambulant patients. The degree of replacement was predominantly correlated to the disease duration, rather than to the onset or the clinical severity. A "COL6-like sandwich sign" was observed in several muscles in ambulant adults, but different involvement of subscapularis, gluteus minimus, and medius changes allowed distinguishing LAMA2-RD from collagenopathies. The thigh muscles seem to be the best ones to assess disease progression. CONCLUSION: WBMRI in LAMA2-RD shows a homogeneous pattern of brain and muscle imaging, representing a supportive diagnostic tool.
- MeSH
- celotělové zobrazování MeSH
- dospělí MeSH
- kosterní svaly diagnostické zobrazování patologie MeSH
- laminin genetika MeSH
- lidé MeSH
- magnetická rezonanční tomografie * metody MeSH
- svalové dystrofie * vrozené diagnostické zobrazování genetika MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: To characterise the pattern and spectrum of involvement on muscle MRI in a large cohort of patients with sarcoglycanopathies, which are limb-girdle muscular dystrophies (LGMD2C-2F) caused by mutations in one of the four genes coding for muscle sarcoglycans. METHODS: Lower limb MRI scans of patients with LGMD2C-2F, ranging from severe childhood variants to milder adult-onset forms, were collected in 17 neuromuscular referral centres in Europe and USA. Muscle involvement was evaluated semiquantitatively on T1-weighted images according to a visual score, and the global pattern was assessed as well. RESULTS: Scans from 69 patients were examined (38 LGMD2D, 18 LGMD2C, 12 LGMD2E and 1 LGMD2F). A common pattern of involvement was found in all the analysed scans irrespective of the mutated gene. The most and earliest affected muscles were the thigh adductors, glutei and posterior thigh groups, while lower leg muscles were relatively spared even in advanced disease. A proximodistal gradient of involvement of vasti muscles was a consistent finding in these patients, including the most severe ones. CONCLUSIONS: Muscle involvement on MRI is consistent in patients with LGMD2C-F and can be helpful in distinguishing sarcoglycanopathies from other LGMDs or dystrophinopathies, which represent the most common differential diagnoses. Our data provide evidence about selective susceptibility or resistance to degeneration of specific muscles when one of the sarcoglycans is deficient, as well as preliminary information about progressive involvement of the different muscles over time.
- MeSH
- dítě MeSH
- dospělí MeSH
- fenotyp MeSH
- kosterní svaly patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- mladiství MeSH
- mutace MeSH
- předškolní dítě MeSH
- sarkoglykanopatie genetika MeSH
- sarkoglykany nedostatek genetika MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa MeSH
- Spojené státy americké MeSH