UvA-DARE (Digital Academic Repository) Limb girdle muscular dystrophies ten Dam, L. Publication date 2020 Document Version Other version License Other Link to publication Citation for published version (APA): ten Dam, L. (2020). Limb girdle muscular dystrophies. General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam (https://dare.uva.nl) Download date:29 Sep 2021 Muscle imaging in inherited and acquired muscle diseases Leroy ten Dam Anneke J. van der Kooi Camiel Verhamme Mike P. Wattjes Marianne de Visser Eur J Neurol. 2016;23:688-703 CHAPTER 2 Chapter 2 ABSTRACT 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. 20 Muscle imaging in inherited and acquired muscle diseases INTRODUCTION In the last decades, neuromuscular imaging has become an important tool in diagnosis, and monitoring of disease progression and treatment of both hereditary and acquired myopathies.1, 2 Muscle imaging in addition to clinical examination and electromyography may support the clinical diagnosis, although muscle biopsy and genetic testing are often 2 Chapter required to establish a definitive diagnosis of hereditary muscle diseases. Muscle imaging can also serve as an aid in distinguishing between different diseases and thus guide genetic testing.3 More practically, by identifying affected muscles, muscle imaging is useful for targeted muscle biopsy.4, 5 The aim of this review is to give a comprehensive overview on the use of magnetic resonance imaging (MRI), ultrasound (US), and advanced muscle imaging techniques [diffusion tensor imaging (DTI), MR-spectroscopy (MRS)] in hereditary and acquired myopathies. Computed tomography (CT) which was for long the only available imaging tool is currently less often used because of its deleterious ionizing radiation effects, and therefore a limited number of publications are included in this review. We shall also 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. METHODS A literature search was performed in PubMed using the terms muscular imaging, magnetic resonance imaging (MeSH), ultrasonography (MeSH) or tomography, X-Ray computed (MeSH) in combination with the different muscle disorders studied. No specific exclusion criteria were formulated. The PubMed search was followed by a manual search in the reference lists of the publications found. ASSESSMENT OF MUSCLE CHANGES In most myopathies, muscle tissue undergoes morphological changes giving rise to replacement of muscle by connective tissue and/or fat. Furthermore, there can be either loss of muscle bulk (atrophy) or enlargement of muscle either by true hypertrophy or by so-called pseudohypertrophy in which enlargement is due to fat deposition. These changes have to be differentiated from physiological changes of muscle tissue during lifetime (e.g. sarcopenia) and are not specific for primary muscle disease as chronically denervated muscles can also show muscle tissue loss and fatty infiltration (e.g. postpolio syndrome).6 In general there is a good correlation between fatty degeneration of muscle tissue and muscle strength (Figure 1, 2).7-11 However, muscle imaging may reveal more abnormalities 21 Chapter 2 as compared to the clinical examination, e.g. in myopathies with a limb girdle distribution of muscle weakness, lumbar paraspinal muscles and to a lesser extent muscles of the lower leg can also show changes on MRI whereas muscle strength is considered to be normal. Sometimes, as in distal myopathies, muscle imaging reveals fewer abnormalities.7 There is great variety as regards the distribution pattern of muscle involvement in hereditary muscle disorders. Pattern recognition on muscle imaging might be helpful in distinguishing between different disease entities. FIGURE 1 | Muscle MRI of ANO5 related muscular dystrophy Axial T1-weighted images of a patient with Miyoshi-like distal myopathy (MMD3) due to a mutation in the ANO5 gene. There is fatty degeneration of the gluteal muscles at the level of the pelvis, in particular the gluteal minimus (GMi) muscles are completely replaced by fat (A), involvement of the posterior and anterior muscles at the level of the thigh (B) and fatty degeneration of the calf muscles (C). 22 Muscle imaging in inherited and acquired muscle diseases MUSCLE IMAGING MODALITIES Computed tomography Computed tomography of skeletal muscles shows the distribution and severity of replacement of muscle tissue by fat and assesses the size of muscle.12, 13 However, compared to other imaging modalities such as MRI and US, muscle CT scan has a number of disadvantages 2 Chapter such as the use of ionizing radiation and lower soft tissue contrast. CT should thus only be performed if there are contraindications to performing MRI, such as cardiac pacemaker, automatic cardioverter defibrillator, ferromagnetic haemostatic clips in the central nervous system, metallic splinter in the eye and other magnetically activated implants.14 Muscle CT scan can serve as an alternative in claustrophobic patients and those unable to lie still for longer periods of time. CT should not be performed in children. Conventional muscle resonance imaging Recently MRI has become the preferred modality for muscle imaging as it has the advantage of achieving a higher soft tissue contrast compared to CT and shows more accurately the distribution of replacement of muscle tissue by fat (Figure 1, 3). FIGURE 3 | Muscle MRI in dystrophinopathy Axial T1-weighted image of the thigh of a patient with Becker muscular dystrophy (BMD). There is predominant fatty degeneration of the posterior compartment, i.e., adductor magnus (AM) and biceps femoris (BF) muscles, with relative sparing of the semitendinosus (ST), gracilis (G) and sartorius (S) muscles. The anterior compartment shows involvement of the lateral (VL) and medial vastus (VM) muscles with relative sparing of the intermedius vastus (VI) and rectus femoris (RF) muscle. This patient was asymptomatic and referred because of hyperCKemia. Another advantage is that specific information can be obtained based on the MRI sequences used. On non-enhanced T1-weighted MRI sequences fatty degeneration of muscle tissue can be assessed. Using fat suppressed T2-weighted or short-tau inversion 23 Chapter 2 recovery (STIR) sequences oedema (focal or diffuse hyperintensity) of skeletal muscles can be detected. However, intramuscular edema is rather non-specific and can be a precursor of muscle damage or inflammation in muscle disease. It may also be found after trauma or overuse of the muscle, in infection, neoplasm, rhabdomyolysis, recent vascular event and even denervation.15-18 Several visual rating scales have been developed allowing a semi- quantitative assessment of the degree and the pattern of fatty muscle degeneration and muscle oedema. However no standardization has taken place. For fatty degeneration the most established rating scale is the five-point rating scale, ranging from stage 0 (normal appearance) to stage 4 (total replacement of muscle tissue by fat and/or connective tissue).19 For assessment of muscle oedema a three-point rating scale is used, with 0 meaning absent, 1 mild and 2 definite muscle oedema.20 Quantification of muscle oedema is possible on T2-weighted images and quantification of fatty degeneration can be achieved in multiple ways, e.g. on T1-weighted images or using Dixon MRI.21 For the latter images fat and water components are separated allowing for calculation of fat fraction. Quantifying fatty degeneration has attained a higher reliability, being less dependent on the observer compared to visual rating scales and easier to reproduce.10 Furthermore, quantification of fatty degeneration can detect traces of fatty degeneration which do not yet result in loss of muscle strength or decrease in functional status making it a useful method to provide longitudinal outcome measures in therapeutic trials. For optimal reproducibility of quantitative MRI in longitudinal studies it is important to use consistent positioning of limbs and to select a site for imaging at a fixed distance from a landmark visible on a scout-image (i.e. knee joint in lower limb muscle imaging).2, 22, 23 Quantitative MRI allows for assessing all muscles in one plane