Specific Pattern Of Muscle Involvement Research Articles

VALUE OF MUSCLE MAGNETIC RESONANCE IMAGING IN COMPARISON WITH MUSCLE BIOPSY FOR DIFFERENTIATING VARIOUS TYPES OF LGMD

Abstract Background Limb Girdle Muscular Dystrophies (LGMD) are a clinically and genetically heterogeneous group of disorders which share progressive muscle weakness and degenerative muscle changes involving the shoulder and pelvic girdle muscles. The diagnostic approach is based on a comprehensive clinical history, a thorough physical examination, laboratory data, electrophysiological investigations, and particularly the histologic and immunoanalysis of a muscle biopsy, followed by a genetic confirmation of the diagnosis. Magnetic Resonance Imaging (MRI) complements clinical examination by delineating characteristic disease specific patterns of muscle involvement which helps in differentiation of individual LGMD subtypes. It is used to demonstrate the severity and distinguish between dystrophic and non-dystrophic diseases. Objective Identification of the value, sensitivity of Muscle MRI to be used as a tool for diagnosis and differentiation of patients with LGMD and as a guidance for the needed immunological and genetic studies to confirm their diagnosis. Patients and methods This study was conducted on 71 patients with clinical criteria of LGMD diagnosed by clinical, laboratory and dystrophic muscle biopsy from Myology Clinic and Neuromuscular Unit, Ain Shams University Hospitals, Muscle MRI was done blind from the results of muscle biopsy, immunohistochemistry and genetic studies. MRI muscles was done at mid-thigh, mid-leg levels. MRI Equipment was 1.5 Tesla in the Radiology department, Ain Shams University Hospitals (T1, Fat subtraction). MRI T1 images were obtained and muscle fatty infiltration in every single muscle was graded on a 5 point rating scale. Results The results showed that the diagnostic performance of muscle MRI in LGMD is most sensitive when calculated in examined Thigh muscles, followed by Leg muscles in comparison with muscle biopsy. Conclusion Muscle MRI is a practical, reproducible and valid tool that can be used in assessment of suspected LGMD patients.

Genotype-Phenotype Correlation of the Childhood-Onset Bethlem Myopathy in the Mediterranean Region of Turkey.

Objectives:Collagen-VI-related myopathies are caused by both dominant and recessive mutations in the three collagen-VI-related genes (COL6A1, COL6A2, and COL6A3) and present as two different major clinical entities; Bethlem myopathy and Ullrich congenital muscular dystrophy.Methods:In this study, we evaluated the clinical, pathologic, and genetic features of 8 patients with Bethlem myopathy from 3 families.Results:We inspected disease course differences with age and mutations. Different variants in COL6A1 and COL6A2 genes were detected. Muscle MRI of the lower limbs showed a specific pattern of muscle involvement with variable severity of fatty infiltration. One family had essential hypertension.Conclusion:Genotype-phenotype correlation studies are critical in determining gene or mutation-targeted therapies, patient follow-up, severity and progression prediction, and genetic counselling.

Global versus individual muscle segmentation to assess quantitative MRI-based fat fraction changes in neuromuscular diseases.

Magnetic resonance imaging (MRI) constitutes a powerful outcome measure in neuromuscular disorders, yet there is a broad diversity of approaches in data acquisition and analysis. Since each neuromuscular disease presents a specific pattern of muscle involvement, the recommended analysis is assumed to be the muscle-by-muscle approach. We, therefore, performed a comparative analysis of different segmentation approaches, including global muscle segmentation, to determine the best strategy for evaluating disease progression. In 102 patients (21 immune-mediated necrotizing myopathy/IMNM, 21 inclusion body myositis/IBM, 10 GNE myopathy/GNEM, 19 Duchenne muscular dystrophy/DMD, 12 dysferlinopathy/DYSF, 7 limb-girdle muscular dystrophy/LGMD2I, 7 Pompe disease, 5 spinal muscular atrophy/SMA), two MRI scans were obtained at a 1-year interval in thighs and lower legs. Regions of interest (ROIs) were drawn in individual muscles, muscle groups, and the global muscle segment. Standardized response means (SRMs) were determined to assess sensitivity to change in fat fraction (ΔFat%) in individual muscles, muscle groups, weighted combinations of muscles and muscle groups, and in the global muscle segment. Global muscle segmentation gave high SRMs for ΔFat% in thigh and lower leg for IMNM, DYSF, LGMD2I, DMD, SMA, and Pompe disease, and only in lower leg for GNEM and thigh for IBM. Global muscle segment Fat% showed to be sensitive to change in most investigated neuromuscular disorders. As compared to individual muscle drawing, it is a faster and an easier approach to assess disease progression. The use of individual muscle ROIs, however, is still of interest for exploring selective muscle involvement. • MRI-based evaluation of fatty replacement in muscles is used as an outcome measure in the assessment of 1-year disease progression in 8 different neuromuscular diseases. • Different segmentation approaches, including global muscle segmentation, were evaluated for determining 1-year fat fraction changes in lower limb skeletal muscles. • Global muscle segment fat fraction has shown to be sensitive to change in lower leg and thigh in most of the investigated neuromuscular diseases.

EP.38Muscle MRI in myotonic dystrophy type 1

Disease-specific patterns of muscle involvement have been detected in several my-opathies. Only few studies reported muscle imaging data on dozens of DM1 patients. The aim of this study is to redefine the muscle involvement in a large cohort of DM1 patients and to search a correlation with clinical and genetic data. Whole body muscle MRI was obtained by more than 70 genetically confirmed DM1 patients. 33 muscle of lower limbs and 18 of upper limbs were considered. Fibrofatty replacement was established by T1 sequences, whereas inflammation was obtained by STIR sequences. Fibro-fatty replacement was more evident in lower limbs than upper limbs. Posterior compartment of the legs was the most affected district. Thighs showed a disto-proximal gradient more evident in hamstrings than in quadriceps. Muscle MRI revealed a specific pattern of muscle involvement in DM1 patients. Statistical correlation between severity of muscle involvement at MRI and clinical severity and genetical backgroud was searched.

Skeletal muscle MRI differentiates SBMA and ALS and correlates with disease severity.

ObjectiveTo investigate the use of muscle MRI for the differential diagnosis and as a disease progression biomarker for 2 major forms of motor neuron disorders: spinal bulbar muscular atrophy (SBMA) and amyotrophic lateral sclerosis (ALS).MethodsWe applied quantitative 3-point Dixon and semiquantitative T1-weighted and short tau inversion recovery (STIR) imaging to bulbar and lower limb muscles and performed clinical and functional assessments in ALS (n = 21) and SBMA (n = 21), alongside healthy controls (n = 16). Acquired images were analyzed for the presence of fat infiltration or edema as well as specific patterns of muscle involvement. Quantitative MRI measurements were correlated with clinical measures of disease severity in ALS and SBMA.ResultsQuantitative imaging revealed significant fat infiltration in bulbar (p < 0.001) and limb muscles in SBMA compared to controls (thigh: p < 0.001; calf: p = 0.001), identifying a characteristic pattern of muscle involvement. In ALS, semiquantitative STIR imaging detected marked hyperintensities in lower limb muscles, distinguishing ALS from SBMA and controls. Finally, MRI measurements correlated significantly with clinical scales of disease severity in both ALS and SBMA.ConclusionsOur findings show that muscle MRI differentiates between SBMA and ALS and correlates with disease severity, supporting its use as a diagnostic tool and biomarker for disease progression. This highlights the clinical utility of muscle MRI in motor neuron disorders and contributes to establish objective outcome measures, which is crucial for the development of new drugs.

Muscle MRI in neutral lipid storage disease (NLSD)

Neutral lipid storage disease (NLSD) is a rare inherited disorder of lipid metabolism resulting in lipid droplets accumulation in different tissues. Skeletal muscle could be affected in both two different form of disease: NLSD with myopathy (NLSD-M) and NLSD with ichthyosis (NLSD-I). We present the muscle imaging data of 12 patients from the Italian Network for NLSD: ten patients presenting NLSD-M and two patients with NLSD-I. In NLSD-M gluteus minimus, semimembranosus, soleus and gastrocnemius medialis in the lower limbs and infraspinatus in the upper limbs were the most affected muscles. Gracilis, sartorius, subscapularis, pectoralis, triceps brachii and sternocleidomastoid were spared. Muscle involvement was not homogenous and characteristic “patchy” replacement was observed in at least one muscle in all the patients. Half of the patients showed one or more STIR positive muscles. In both NLSD-I cases muscle involvement was not observed by T1-TSE sequences, but one of them showed positive STIR images in more than one muscle in the leg. Our data provides evidence that muscle imaging can identify characteristic alterations in NLSD-M, characterized by a specific pattern of muscle involvement with “patchy” areas of fatty replacement. Larger cohorts are needed to assess if a distinct pattern of muscle involvement exists also for NLSD-I.

Muscle MRI in Duchenne muscular dystrophy: Evidence of a distinctive pattern

The purpose of this study was to describe the pattern of muscle involvement using MRI findings and correlate with functional as well as muscle strength measurements. Fifty genetically confirmed DMD children with a mean age of 7.6 ± 2.8 (4–15 years) underwent muscle MRI and qualitative assessment was done for muscle changes using Mercuri staging for fibro-fatty replacement on T1 sequence and Borsato score for myoedema on STIR sequence. Detailed phenotypic characterisation was done with Manual muscle testing (modified MRC grading) and Muscular Dystrophy Functional Rating Scale (MDFRS). Mercuri scoring showed severe fibro-fatty changes in Gluteus medius, minimus and Adductor magnus followed by moderate to severe changes in Gluteus maximus and Quadriceps muscles. Total sparing of Gracilis, Sartorius and Semimembranosus muscles was observed. Superficial posterior and lateral leg muscles were preferentially involved with sparing of deep posterior and anterior leg muscles. Myoedema showed significant inverse correlation with fatty infiltration in thigh muscles. Similarly, significant inverse correlation was observed between Mercuri scores and MRC grading as well as MDFRS scores. A direct linear correlation was observed between duration of illness and fibro-fatty changes in piriformis, quadriceps and superficial posterior leg muscles. There was no correlation between MRI findings and genotypic characteristics. However, this specific pattern of muscle involvement in MRI could aid in proceeding for genetic testing when clinical suspicion is high, thus reducing the need for muscle biopsy. Fibro fatty infiltration as measured by Mercuri scoring can be a useful marker for assessing the disease severity and progression.

A study on the bifurcation of sciatic nerve with clinical significance

The purpose of this study was to describe the pattern of muscle involvement using MRI findings and correlate with functional as well as muscle strength measurements. Fifty genetically confirmed DMD children with a mean age of 7.6 ± 2.8 (4–15 years) underwent muscle MRI and qualitative assessment was done for muscle changes using Mercuri staging for fibro-fatty replacement on T1 sequence and Borsato score for myoedema on STIR sequence. Detailed phenotypic characterisation was done with Manual muscle testing (modified MRC grading) and Muscular Dystrophy Functional Rating Scale (MDFRS). Mercuri scoring showed severe fibro-fatty changes in Gluteus medius, minimus and Adductor magnus followed by moderate to severe changes in Gluteus maximus and Quadriceps muscles. Total sparing of Gracilis, Sartorius and Semimembranosus muscles was observed. Superficial posterior and lateral leg muscles were preferentially involved with sparing of deep posterior and anterior leg muscles. Myoedema showed significant inverse correlation with fatty infiltration in thigh muscles. Similarly, significant inverse correlation was observed between Mercuri scores and MRC grading as well as MDFRS scores. A direct linear correlation was observed between duration of illness and fibro-fatty changes in piriformis, quadriceps and superficial posterior leg muscles. There was no correlation between MRI findings and genotypic characteristics. However, this specific pattern of muscle involvement in MRI could aid in proceeding for genetic testing when clinical suspicion is high, thus reducing the need for muscle biopsy. Fibro fatty infiltration as measured by Mercuri scoring can be a useful marker for assessing the disease severity and progression.

Muscle imaging in inherited and acquired muscle diseases.

In this review we discuss the use of conventional (computed tomography, magnetic resonance imaging, ultrasound) and advanced muscle imaging modalities (diffusion tensor imaging, magnetic resonance spectroscopy) in hereditary and acquired myopathies. We summarize the data on specific patterns of muscle involvement in the major categories of muscle disease and provide recommendations on how to use muscle imaging in this field of neuromuscular disorders.

Clinical and muscle imaging findings in 14 mainland chinese patients with oculopharyngodistal myopathy.

Oculopharyngodistal myopathy (OPDM) is an extremely rare, adult-onset hereditary muscular disease characterized by progressive external ocular, pharyngeal, and distal muscle weakness and myopathological rimmed vacuole changes. The causative gene is currently unknown; therefore, diagnosis of OPDM is based on clinical and histopathological features and genetic exclusion of similar conditions. Moreover, variable manifestations of this disorder are reported in terms of muscle involvement and severity. We present the clinical profile and magnetic resonance imaging (MRI) changes of lower limb muscles in 14 mainland Chinese patients with OPDM, emphasizing the role of muscle MRI in disease identification and differential diagnosis. The patients came from 10 unrelated families and presented with progressive external ocular, laryngopharyngeal, facial, distal limb muscle weakness that had been present since early adulthood. Serum creatine kinase was mildly to moderately elevated. Electromyography revealed myogenic changes with inconsistent myotonic discharge. The respiratory function test revealed subclinical respiratory muscle involvement. Myopathological findings showed rimmed vacuoles with varying degrees of muscular dystrophic changes. All known genes responsible for distal and myofibrillar myopathies, vacuolar myopathies, and muscular dystrophies were excluded by PCR or targeted next-generation sequencing. Muscle MRI revealed that the distal lower legs had more severe fatty replacement than the thigh muscles. Serious involvement of the soleus and long head of the biceps femoris was observed in all patients, whereas the popliteus, gracilis and short head of biceps femoris were almost completely spared, even in advanced stages. Not only does our study widen the spectrum of OPDM in China, but it also demonstrates that OPDM has a specific pattern of muscle involvement that may provide valuable information for its differential diagnosis and show further evidence supporting the conclusion that OPDM is a unique disease phenotype.

Quantitative Magnetic Resonance Imaging in Limb-Girdle Muscular Dystrophy 2I: A Multinational Cross-Sectional Study

We conducted a prospective multinational study of muscle pathology using magnetic resonance imaging (MRI) in patients with limb-girdle muscular dystrophy 2I (LGMD2I). Thirty eight adult ambulant LGMD2I patients (19 male; 19 female) with genetically identical mutations (c.826C>A) in the fukutin-related protein (FKRP) gene were recruited. In each patient, T1-weighted (T1w) imaging was assessed by qualitative grading for 15 individual lower limb muscles and quantitative Dixon imaging was analysed on 14 individual lower limb muscles by region of interest analysis. We described the pattern and appearance of muscle pathology and gender differences, not previously reported for LGMD2I. Diffuse fat infiltration of the gastrocnemii muscles was demonstrated in females, whereas in males fat infiltration was more prominent in the medial than the lateral gastrocnemius (p = 0.05). In the anterior thigh of males, in contrast to females, median fat infiltration in the vastus medialis muscle (45.7%) exceeded that in the vastus lateralis muscle (11.2%) (p<0.005). MRI is non-invasive, objective and does not rely on patient effort compared to clinical and physical measures that are currently employed. We demonstrated (i) that the quantitative Dixon technique is an objective quantitative marker of disease and (ii) new observations of gender specific patterns of muscle involvement in LGMD2I.

Pompe’s Disease in Siblings Taking Enzyme Replacement Therapy: Skeletal Muscle Magnetic Resonance Imaging Findings

Pompe’s disease is a rare inherited muscle disorder resulting from deficiency of lysosomal acid α-glucosidase. This report describes the muscle magnetic resonance imaging findings in two young adults with late-onset Pompe’s disease. A specific pattern of muscle involvement has been described in multiple inherited muscle disorders, including Pompe’s disease. With the advent of enzyme replacement therapy, increased utilisation of imaging for diagnosis, monitoring of disease progress, and treatment response are expected. This article emphasises the importance of magnetic resonance imaging in screening the skeletal muscle in this disease and describes the development of new imaging techniques.

Muscle magnetic resonance imaging involvement in muscular dystrophies with rigidity of the spine

The aim of the study was to evaluate whether the visual analysis of muscle magnetic resonance imaging scans can identify specific patterns of muscle involvement. We assessed scans from 83 patients with muscle disorders characterized by rigidity of the spine secondary to mutations in 4 different genes. The conditions studied were rigid spine syndrome (SEPN1 defects), Bethlem myopathy, and Ullrich congenital muscular dystrophy, allelic disorders caused by Col6A1, Col6A2, and Col6A3 mutations, the autosomal dominant form of Emery-Dreifuss muscular dystrophy (LMNA defects) and calpain-deficient limb girdle muscular dystrophy (CAPN3 defects). The scans of 25 patients affected by other myopathies were also reviewed as a control group. The scans were compared with the previously described patterns. In 82% of the scans in the study group (68/83) the patterns were classified as "typical" of 1 of the 5 forms studied, and in 7 (8%) were consistent with 1 of the reported patterns but not entirely typical. With one exception, the patterns identified were always consistent with the appropriate genetic diagnosis. The remaining scans (9%) had only minimal changes and were uninformative. None of the scans of the 25 patients in the control group had patterns that could be classified as typical of the 5 forms examined. The sensitivity to detect selective patterns in relation to the genetic diagnosis was 0.9. These findings suggest that muscle magnetic resonance imaging could be used in clinical practice as an additional tool in the differential diagnosis of muscle disorders with prominent spinal rigidity.

M.P.5.03 Specificity and sensitivity of patterns of muscle MRI involvement in muscular dystrophies with rigidity of the spine

The aim of the study was to evaluate the sensitivity and specificity of visual analysis of muscle MRI scans to identify specific patterns of muscle involvement. We assessed scans from 83 patients with muscular dystrophies characterized by rigidity of the spine and other clinically overlapping features, secondary to mutations in four different genes. The conditions studied were Rigid Spine syndrome 1 (RSMD1) due to mutations in the SEPN 1 gene, Bethlem myopathy and Ullrich congenital muscular dystrophy, allelic disorders due to Col6A gene mutations, autosomal dominant Emery Dreifuss muscular dystrophy (LMNA gene defects) and calpain deficient limb girdle muscular dystrophy (LGMD2A), due to mutations in CAPN3.

111th ENMC International Workshop on Multi-minicore Disease. 2nd International MmD Workshop, 9–11 November 2002, Naarden, The Netherlands

111th ENMC International Workshop on Multi-minicore Disease. 2nd International MmD Workshop, 9–11 November 2002, Naarden, The Netherlands

Muscle MRI findings in a three-generation family affected by Bethlem myopathy

We report clinical and muscle magnetic resonance imaging (MRI) findings in three individuals (aged 6, 26 and 73 years) from a three-generation family with Bethlem myopathy, confirmed by molecular genetic analysis which showed an exon skipping mutation in the COL6A1 gene. The clinical severity ranged from mild proximal weakness and distal laxity in the younger patients, to inability to stand or walk and severe contractures in the 76-year-old grandmother. The pattern of muscle involvement showed variable severity in parallel with the severity of motor function impairment. Although there was a marked variability in the severity of the MRI findings, it was possible to recognize a specific pattern of muscle involvement in all three patients. This consisted of involvement of the peripheral region of the vastus lateralis and hamstrings muscles with relative sparing of their central part. This was best appreciated in the third decade of life, but could also be identified both in the younger patient with minimal MRI changes and in the oldest patient, despite her more severe and diffuse muscle involvement. This report suggests that muscle MRI could be used as an additional tool to establish the pattern and the degree of muscle involvement in patients with Bethlem myopathy. Further studies in a larger cohort are needed to evaluate the specificity of these findings.

A short protocol for muscle MRI in children with muscular dystrophies.

The use of muscle magnetic resonance imaging in patients with muscular dystrophies or congenital myopathies has been limited. We describe the development of a short protocol to be used in young patients with neuromuscular disorders. The protocol includes transverse T1-weighted spin echo sequence images of thighs and calves. The total scanning time is less than 30 minutes, and can be easily applied to patients over the age of 4 years without any need for sedation. Although only the leg muscles are imaged, the images obtained can still help to identify specific patterns of muscle involvement and provide additional help in the differential diagnosis of muscle disorders with overlapping clinical features.

Selective muscle involvement on magnetic resonance imaging in autosomal dominant Emery-Dreifuss muscular dystrophy.

The aim of this study was to evaluate the spectrum of muscle involvement on MRI in patients with autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD2) due to mutations in the lamin A/C gene and to compare it to the pattern found in other conditions with similar phenotype. Nine patients with a diagnosis of EDMD2 had MRI scanning of their leg muscles. Seven other patients, four with the X-linked form of Emery-Dreifuss muscular dystrophy (EDMD) and three with an Emery-Dreifuss-like phenotype but no detectable mutations in either the emerin or the lamin A/C gene were also scanned as disease controls. All patients with EDMD2 showed a characteristic involvement of the posterior calf muscles. The medial head of the gastrocnemius was always predominantly involved while the lateral head was relatively spared. This pattern was more obvious in mildly affected patients in whom the other calf muscles were spared or only mildly involved but was also recognisable in the patients with more advanced disease. In contrast, none of the patients with the X-linked EDMD or with Emery-Dreifuss-like phenotype but no mutation in either genes showed this pattern of muscle involvement. Our results suggest that patients with EDMD2 have a specific pattern of muscle involvement and that muscle MRI can be used, in combination with other techniques, to distinguish various genetic forms of Emery-Dreifuss muscular dystrophy.