Thigh and Leg Muscle MRI Findings in GNE Myopathy

Background: Muscle MRI protocols have been developed to assess muscle involvement in a wide variety of muscular dystrophies. Different muscular dystrophies can involve muscle groups in characteristic patterns. These patterns can be identified in muscle MRI in the form of fatty infiltration. Objective: This study was conducted to add the existing knowledge of muscle MRI in GNE myopathy and evaluate the correlation of muscular involvement with different gene mutations. Methods: The MRI scans of the 18 GNE patients were analyzed retrospectively. Cluster analysis was done for grouping the muscles and patients. Results: The four muscles with the highest fat infiltration were adductor magnus, tibialis anterior, semitendinosus, and semimembranosus. Furthermore, three clusters of muscle involvement were found, including cluster 1, typical muscle involvement indicating muscles with the highest infiltration: extensor digitorum longus, gracilis, biceps femoris, soleus, gastrocnemius medial, adductor longus, tibialis anterior, adductor magnus, semimembranosus, semitendinosus; cluster 2, less typical muscle involvement indicating muscles with intermediate fat infiltration, peroneus longus, gastrocnemius lateral, and minimal fat infiltration in most of the patients, i.e., tibialis posterior; and cluster 3, atypical muscle involvement with low-fat infiltration: rectus femoris, sartorius, vastus intermedius, vastus medialis, and vastus lateralis. Conclusions: This study found three clusters of muscle involvement and three groups of patients among GNE patients. Hamstring muscles and the anterior compartment of the lower leg were the muscles with the highest fat infiltration. Moreover, a weak genotype-muscle MRI association was found in which tibialis posterior was more involved in patients with the most frequent mutation, i.e., C.2228T > C (p.M743T) mutation; however, this finding may be related to longer disease duration.

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Correlation Between Quantitative MRI and Muscle Histopathology in Muscle Biopsies from Healthy Controls and Patients with IBM, FSHD and OPMD

Journal of Neuromuscular Diseases ◽

10.3233/jnd-200543 ◽

2020 ◽

Vol 7 (4) ◽

pp. 495-504

Author(s):

Saskia Lassche ◽

Benno Küsters ◽

Arend Heerschap ◽

Maxime V.P. Schyns ◽

Coen A.C. Ottenheijm ◽

...

Keyword(s):

Tibialis Anterior ◽

Vastus Lateralis ◽

Fatty Infiltration ◽

Quantitative Mri ◽

Muscle Disease ◽

Healthy Controls ◽

Muscle Mri ◽

Severity Grading ◽

Scale Range ◽

Muscle Biopsies

Background: Muscle MRI is increasingly used as a diagnostic and research tool in muscle disorders. However, the correlation between MRI abnormalities and histopathological severity is largely unknown. Objective: To investigate correlations between muscle MRI abnormalities and histopathological severity in healthy controls and patients with muscle disease. Methods: We performed quantitative MRI and histopathological analysis in 35 patients with inclusion body myositis, facioscapulohumeral muscular dystrophy or oculopharyngeal muscular dystrophy and 12 healthy controls. Participants contributed needle biopsies of the vastus lateralis and/or tibialis anterior, yielding 77 muscle biopsies with matched T1, T2 and TIRM MRI imaging. Muscle biopsies were evaluated with a semi-quantitative histopathology severity grading scale (range 0–12) and an inflammation severity grading scale (range 0–3). Results: In muscle disease, histopathology sum scores ranged from 0 to 11 and correlated significantly with fat percentage as measured on MRI (Spearman’s rho = 0.594, p < 0.001). Muscle edema on muscle MRI was associated with increased amounts of inflammation (p < 0.001). Mild abnormalities occured in 95% of control biopsies and were more pronounced in tibialis anterior (median sum score of 1±1 in vastus lateralis and 2±1 in tibialis anterior (p = 0.048)). Conclusion: In muscle disease, fatty infiltration on MRI correlates moderately with muscle histopathology. Histopathological abnormalities can occur prior to the onset of fatty infiltration. In middle-aged controls, almost all biopsies showed some histopathological abnormalities. The findings from this study may facilitate the choice for appropriate imaging sequences as outcome measures in therapeutic trials.

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Whole-Body Muscle MRI Characteristics of LAMA2 Gene Mutation Congenital Muscular Dystrophy Children

10.1101/2021.03.27.21254399 ◽

2021 ◽

Author(s):

Hossam M. Sakr ◽

Nagia Fahmy ◽

Nermine S. Elsayed ◽

Hala Abdulhady ◽

Tamer A. El-Sobky ◽

...

Keyword(s):

Muscular Dystrophy ◽

Fatty Infiltration ◽

Congenital Muscular Dystrophy ◽

Whole Body ◽

Control Group ◽

Muscle Mri ◽

Muscle Involvement ◽

Muscle Diseases ◽

Body Muscle ◽

Index Group

Merosin-deficient or LAMA2-related congenital muscular dystrophy (CMD) belongs to a group of muscle diseases with an overlapping diagnostic spectrum. MRI plays an important role in the diagnosis and disease-tracking of muscle diseases. Whole-body MRI is ideal for describing patterns of muscle involvement. Our purpose is to analyze the pattern of muscle involvement in merosin-deficient CMD children employing whole-body muscle MRI. Ten children with merosin-deficient CMD underwent whole-body muscle MRI. We used a control group of other hereditary muscle diseases, which included 13 children. Overall, 37 muscles were graded for fatty infiltration using Mercuri scale modified by Fischer et al 2008. The results showed a fairly consistent pattern of muscle fatty infiltration in index group, which differed from that in control group. There was a highly statistically significant difference between the two groups in regard to the fatty infiltration of the neck, serratus anterior, rotator cuff, deltoid, forearm, gluteus maximus, gluteus medius, gastrocnemius and soleus muscles. Additionally, results showed relative sparing of the brachialis, biceps brachii, gracilis, sartorius, semitendinosus and extensor muscles of the ankle in index group. There is evidence to suggest that whole-body muscle MRI can become a useful contributor to the differential diagnosis of merosin deficient CMD.

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

Neurology ◽

10.1212/wnl.0000000000008009 ◽

2019 ◽

Vol 93 (9) ◽

pp. e895-e907 ◽

Cited By ~ 12

Author(s):

Uros Klickovic ◽

Luca Zampedri ◽

Christopher D.J. Sinclair ◽

Stephen J. Wastling ◽

Karin Trimmel ◽

...

Keyword(s):

Motor Neuron ◽

Disease Progression ◽

Disease Severity ◽

Lower Limb ◽

Muscle Mri ◽

Muscle Involvement ◽

Fat Infiltration ◽

Lower Limb Muscles ◽

Limb Muscles ◽

Mri Measurements

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.

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Value of muscle magnetic resonance imaging in the differential diagnosis of muscular dystrophies related to the dystrophin-glycoprotein complex

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-019-1242-y ◽

2019 ◽

Vol 14 (1) ◽

Cited By ~ 2

Author(s):

Zhiying Xie ◽

Zhihao Xie ◽

Meng Yu ◽

Yiming Zheng ◽

Chengyue Sun ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Differential Diagnosis ◽

Fatty Infiltration ◽

Muscular Dystrophies ◽

Resonance Imaging ◽

Muscle Mri ◽

Glycoprotein Complex ◽

Dystrophin Glycoprotein Complex ◽

Muscle Magnetic Resonance Imaging ◽

Dystrophin Glycoprotein

Abstract Background Dystrophin-glycoprotein complex (DGC)-related muscular dystrophies may present similar clinical and pathological features as well as undetectable mutations thus being sometimes difficult to distinguish. We investigated the value of muscle magnetic resonance imaging (MRI) in the differential diagnosis of DGC-related muscular dystrophies and reported the largest series of Chinese patients with sarcoglycanopathies studied by muscle MRI. Results Fifty-five patients with DGC-related muscular dystrophies, including 22 with confirmed sarcoglycanopathies, 11 with limb-girdle muscular dystrophy 2I (LGMD2I, FKRP-associated dystroglycanopathy), and 22 with dystrophinopathies underwent extensive clinical evaluation, muscle biopsies, genetic analysis, and muscle MRI examinations. Hierarchical clustering of patients according to the clinical characteristics showed that patients did not cluster according to the genotypes. No statistically significant differences were observed between sarcoglycanopathies and LGMD2I in terms of thigh muscle involvement. The concentric fatty infiltration pattern was observed not only in different sarcoglycanopathies (14/22) but also in LGMD2I (9/11). The trefoil with single fruit sign was observed in most patients with dystrophinopathies (21/22), and a few patients with sarcoglycanopathies (4/22) or LGMD2I (2/11). Hierarchical clustering showed that most patients with sarcoglycanopathies or LGMD2I can be distinguished from dystrophinopathies based on the concentric fatty infiltration pattern and trefoil with single fruit sign at the thigh level on muscle MRI. Conclusions Muscle MRI at the thigh level potentially allows distinction of sarcoglycanopathies or FKRP-associated dystroglycanopathy from dystrophinopathies.

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Skeletal muscle magnetic resonance biomarkers in GNE myopathy

Neurology ◽

10.1212/wnl.0000000000011231 ◽

2020 ◽

pp. 10.1212/WNL.0000000000011231

Author(s):

Chia-Ying Liu ◽

Jianhua Yao ◽

William C. Kovacs ◽

Joseph A. Shrader ◽

Galen Joe ◽

...

Keyword(s):

Skeletal Muscle ◽

Relaxation Time ◽

Magnetic Resonance ◽

Disease Severity ◽

Muscle Volume ◽

Stage I ◽

Thigh Muscle ◽

Muscle Involvement ◽

Fat Infiltration ◽

Gne Myopathy

ObjectivesTo characterize muscle involvement and evaluate disease severity in patients with GNE myopathy using skeletal muscle MRI and proton magnetic resonance spectroscopy (1H-MRS).MethodsSkeletal muscle imaging of the lower extremities was performed in 31 patients with genetically confirmed GNE myopathy, including T1-weighted and STIR images, T1 and T2 mapping and 1H-MRS. Measures evaluated included longitudinal relaxation time (T1), transverse relaxation time (T2), and 1H-MRS fat fraction (FF). Thigh muscle volume was correlated with relevant measures of strength, function, and patient-reported outcomes.ResultsThe cohort was representative of a wide range of disease progression. Contractile thigh muscle volume ranged from 5.51% to 62.95%, and correlated with thigh strength (r = 0.91), the 6-minute walk test (r = 0.82), the adult myopathy assessment tool (r = 0.83), the activities-specific balance confidence scale (r = 0.65), and the inclusion body myositis functional rating scale (r = 0.62). Four stages of muscle involvement were distinguished by qualitative (T1W and STIR images) and quantitative methods: stage I) Unaffected muscle (T1 = 1,033 ± 74.2 ms, T2 = 40.0 ± 1.9 ms, FF = 7.4 ± 3.5%); Stage II) STIR hyperintense muscle with minimal or no fat infiltration (T1 = 1,305 ± 147 ms, T2 = 50.2 ± 3.5 ms, FF = 27.6 ± 12.7%); Stage III) Fat infiltration and STIR hyperintensity (T1 = 1,209 ± 348 ms, T2 = 73.3 ± 12.6 ms, FF = 57.5 ± 10.6%); and Stage IV) Complete fat replacement (T1 = 318 ± 39.9 ms, T2 = 114 ± 21.2 ms, FF = 85.6 ± 4.2%). 1H-MRS showed a significant decrease in intramyocellular lipid and trimethylamines (TMA) between stage I and II, suggesting altered muscle metabolism at early stages.ConclusionMRI biomarkers can monitor muscle involvement and determine disease severity non-invasively in patients with GNE myopathy.ClinicalTrials.gov IdentifierNCT01417533.

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

QJM ◽

10.1093/qjmed/hcab102.022 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Sarah M Ihab ◽

Doaa A El-aidy ◽

Khaled A Ahmed ◽

Nagia A Fahmy

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Muscle Biopsy ◽

Rating Scale ◽

Fatty Infiltration ◽

Resonance Imaging ◽

University Hospitals ◽

Muscle Mri ◽

Muscle Involvement ◽

Genetic Studies

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.

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Muscle MRI as a Useful Biomarker in Hereditary Transthyretin Amyloidosis: A Pilot Study

Genes ◽

10.3390/genes12111786 ◽

2021 ◽

Vol 12 (11) ◽

pp. 1786

Author(s):

Guido Primiano ◽

Tommaso Verdolotti ◽

Gabriella D’Apolito ◽

Andrea Di Paolantonio ◽

Valeria Guglielmino ◽

...

Keyword(s):

Linear Regression Analysis ◽

Fatty Infiltration ◽

Inverse Correlation ◽

Transthyretin Amyloidosis ◽

Muscle Mri ◽

Muscle Involvement ◽

Disease Modifying Therapies ◽

Severity Of The Disease ◽

Hereditary Transthyretin Amyloidosis

Hereditary transthyretin amyloidosis (ATTRv, v for variant) is a severe and heterogeneous multisystem condition with a prevalent peripheral nervous system impairment, due to mutations in the transthyretin gene. Considering the introduction of different disease-modifying therapies in the last few years, a need of reliable biomarkers is emerging. In this study, we evaluated muscle MRI in a cohort of ATTRv patients in order to establish if the severity of muscle involvement correlated with disease severity. Linear regression analysis showed a significant positive correlation between the total fatty infiltration score and NIS, NIS-LL, and Norfolk, and an inverse correlation with Sudoscan registered from feet. In conclusion, we demonstrated the role of muscle MRI in ATTRv as possible disease biomarker, both for diagnostic purposes and for assessing the severity of the disease.

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

10.1101/486910 ◽

2018 ◽

Author(s):

Uros Klickovic ◽

Luca Zampedri ◽

Christopher Sinclair ◽

Stephen Wastling ◽

Karin Trimmel ◽

...

Keyword(s):

Motor Neuron ◽

Disease Progression ◽

Disease Severity ◽

Lower Limb ◽

Muscle Mri ◽

Muscle Involvement ◽

Fat Infiltration ◽

Lower Limb Muscles ◽

Limb Muscles ◽

Mri Measurements

Objective: To investigate the use of muscle MRI for the differential diagnosis and as a disease progression biomarker for two major forms of motor neuron disorders, spinal bulbar muscular atrophy (SBMA) and amyotrophic lateral sclerosis (ALS). Methods: We applied quantitative 3-point Dixon and semi-quantitative T1-weighted and STIR imaging to bulbar and lower limb muscles and performed clinical and functional assessments in ALS (n=21) and SBMA (n=21) patients, 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 parameters of disease severity in ALS and SBMA. Results: Quantitative 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, semi-quantitative STIR imaging detected marked hyperintensities in lower limb muscles, distinguishing ALS from SBMA and controls. Lastly, MRI measurements correlated significantly with clinical scales of disease severity in both ALS and SBMA. Conclusions: Our 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.

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Muscle MRI in a large cohort of patients with oculopharyngeal muscular dystrophy

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2018-319578 ◽

2018 ◽

Vol 90 (5) ◽

pp. 576-585 ◽

Cited By ~ 9

Author(s):

Alicia Alonso-Jimenez ◽

Rosemarie H M J M Kroon ◽

Aida Alejaldre-Monforte ◽

Claudia Nuñez-Peralta ◽

Corinne G C Horlings ◽

...

Keyword(s):

Muscular Dystrophy ◽

Clinical Data ◽

Genetic Disorder ◽

Muscle Pathology ◽

Oculopharyngeal Muscular Dystrophy ◽

Imaging Studies ◽

Muscle Mri ◽

Muscle Involvement ◽

Adductor Magnus ◽

Fatty Replacement

Background and objectiveOculopharyngeal muscular dystrophy (OPMD) is a genetic disorder caused by an abnormal expansion of GCN triplets within the PABPN1 gene. Previous descriptions have focused on lower limb muscles in small cohorts of patients with OPMD, but larger imaging studies have not been performed. Previous imaging studies have been too small to be able to correlate imaging findings to genetic and clinical data.MethodsWe present cross-sectional, T1-weighted muscle MRI and CT-scan data from 168 patients with genetically confirmed OPMD. We have analysed the pattern of muscle involvement in the disease using hierarchical analysis and presented it as heatmaps. Results of the scans were correlated with genetic and clinical data.ResultsFatty replacement was identified in 96.7% of all symptomatic patients. The tongue, the adductor magnus and the soleus were the most commonly affected muscles. Muscle pathology on MRI correlated positively with disease duration and functional impairment.ConclusionsWe have described a pattern that can be considered characteristic of OPMD. An early combination of fat replacement in the tongue, adductor magnus and soleus can be helpful for differential diagnosis. The findings suggest the natural history of the disease from a radiological point of view. The information generated by this study is of high diagnostic value and important for clinical trial development.

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Role of CMR Imaging in Diagnostics and Evaluation of Cardiac Involvement in Muscle Dystrophies

Current Heart Failure Reports ◽

10.1007/s11897-021-00521-2 ◽

2021 ◽

Author(s):

Edyta Blaszczyk ◽

Jan Gröschel ◽

Jeanette Schulz-Menger

Keyword(s):

Clinical Care ◽

Fatty Infiltration ◽

Severe Heart Failure ◽

Diffuse Fibrosis ◽

Muscular Dystrophies ◽

Invasive Technique ◽

Myocardial Tissue ◽

Therapeutic Decisions ◽

Cardiovascular Evaluation ◽

Unique Capability

Abstract Purpose of Review This review aims to outline the utility of cardiac magnetic resonance (CMR) in patients with different types of muscular dystrophies for the assessment of myocardial involvement, risk stratification and in guiding therapeutic decisions. Recent Findings In patients suffering from muscular dystrophies (MD), even mild initial dysfunction may lead to severe heart failure over a time course of years. CMR plays an increasing role in the diagnosis and clinical care of these patients, mostly due to its unique capability to precisely characterize subclinical and progressive changes in cardiac geometry, function in order to differentiate myocardial injury it allows the identification of inflammation, focal and diffuse fibrosis as well as fatty infiltration. CMR may provide additional information in addition to the physical examination, laboratory tests, ECG, and echocardiography. Summary Further trials are needed to investigate the potential impact of CMR on the therapeutic decision-making as well as the assessment of long-term prognosis in different forms of muscular dystrophies. In addition to the basic cardiovascular evaluation, CMR can provide a robust, non-invasive technique for the evaluation of subclinical myocardial tissue injury like fat infiltration and focal and diffuse fibrosis. Furthermore, CMR has a unique capability to detect the progression of myocardial tissue damage in patients with a preserved systolic function.

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