revue neurologique 179 (2023) 61–80

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Original article

Contribution of muscle MRI for diagnosis of

myopathy

N. Venturelli a,*,
M. Tordjman a, A. Ammar a, A. Chetrit a, V. Renault a, R.-Y. Carlier a,b
a
AP–HP, GHU Paris-Saclay, DMU Smart Imaging, Medical imaging department, Raymond-Poincaré teaching hospital,
104, boulevard Raymond-Poincaré, 92380 Garches, France
b
UMR 1179 End:Icap, UVSQ-Paris-Saclay University, Paris, France

info article abstract

Keywords: Inherited myopathies are a group of disease, which, although distinct from a genetic and
Whole-body muscle MRI prognostic point of view, can lead to non-specific clinical pictures due to phenotypic overlap.
Congenital myopathy Acquired immuno-mediated myopathies may also pose the problem of clinically accurate
Acquired myopathy etiological orientation. The assessment of fatty infiltration and pathological increase in
Involvement patterns water volume of the muscle contingent on whole-body muscle MRI is becoming increasingly
important in aiding the initial diagnosis of inherited and acquired myopathies. MRI helps
orientating the clinical diagnostic hypotheses thanks to the patterns of muscle involved
(more or less specific according to the entities), which led to the development of decision-
making algorithms proposed in the literature. The aim of this article is to specify the proper
MRI protocol for the evaluation of myopathies and the basis of the interpretation and to
provide a summary of the most frequently inherited and acquired myopathies described in
the literature.
# 2022 The Authors. Published by Elsevier Masson SAS. This is an open access article under
the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

1. Introduction Inherited myopathies, are usually divided in three main

categories, including multiple sub-categories (Fig. 1):
Myopathy is a generic term for any pathological primary
muscle damage, regardless of the pathogenic mechanism  muscular dystrophies, caused by genetic mutations that
involved. alter the primary structure of the muscle fibers, which will
There are two main types of myopathies: inherited gradually break down;
myopathies secondary to a genetic abnormality, and acquired  congenital myopathies, due to a defect in the development
myopathies, affecting an initially healthy muscle and not or maturation of muscle fibers during the fetal period,
related to a genetic anomaly. caused by a genetic anomaly;

* Corresponding author.
E-mail address: [email protected] (N. Venturelli).
https://doi.org/10.1016/j.neurol.2022.12.002
0035-3787/# 2022 The Authors. Published by Elsevier Masson SAS. This is an open access article under the CC BY-NC-ND license (http://
creativecommons.org/licenses/by-nc-nd/4.0/).
62 revue neurologique 179 (2023) 61–80

Fig. 1 – Classification of inherited myopathies.

 metabolic myopathies, due to a genetically determined entities, and delayed genetic results. Thus, the final diagnosis
dysfunction of the sugar degradation pathway, of the often takes years, and any complementary diagnostic tool
respiratory metabolic chain or of fat metabolism. helping to achieve faster diagnosis is useful. Whole-body
muscle magnetic resonance imaging (MRI) has acquired a
Acquired myopathies include four main categories (Fig. 2) growing role in the diagnosis and evaluation of myopathies,
[1]:metabolic myopathies, due to a genetically determined especially in inherited myopathies that often present a
dysfunction of the sugar degradation pathway, of the relatively orienting imaging pattern of damage. MRI is non-
respiratory metabolic chain or of fat metabolism. invasive, non-irradiating and allows an exhaustive analysis of
all the body’s muscle masses in a single examination.
 idiopathic inflammatory myopathies; Technical improvements have enabled more precise, quicker
 toxic myopathies; and more accessible examinations. Whole-body MRI indica-
 infectious myopathies; tions have grown over the last twenty years, both to assess
 endocrine myopathies. initial diagnostic hypotheses and to monitor disease progres-
sion. This examination can be performed at any age but
Myopathies, and in particular inherited myopathies, are requires a rigorous acquisition and interpretation technique
rare, with great phenotypic overlap between the different and must be performed by a trained team for better diagnostic
yield.

2. Whole-body muscle MRI

2.1. Indications in myopathy assessment

Whole-body muscle MRI is useful for two main types of

indications:

 to orientate the initial diagnosis, allowing a better prescrip-

tion of additional examinations (genetic/biologic);
 to follow the disease course and monitor response to
treatment.

2.1.1. Initial diagnosis

Whole-body muscle MRI can be valuable in several situations:

 when the phenotypic presentation points clinically towards

several groups of myopathies due to non-specific symp-
toms, muscle MRI can show a characteristic pattern of
muscle involvement restricting the genetic panels to be
carried out to reach a final diagnosis. This examination also
provides additional clues in favor or against a given
Fig. 2 – Classification of acquired myopathies. myopathy by analyzing non-muscular structures (brain,
 revue neurologique 179 (2023) 61–80 63

soft tissue) (abnormalities of the cerebral white matter disabled and may be very young. Particular attention should
pointing to certain pathologies, evidence of deep neoplasia be given to reassuring claustrophobic patients or young
in the assessment of dermatopolymyositis which may be of children during the examination in order to achieve good
neoplastic origin); image quality, with no movement artifacts. The presence of
 when the diagnosis of myopathy is clinically obvious, but young patients’ parents during the examination should be
the first confirmatory examinations (muscle biopsy, genetic encouraged, as some MRI machines have large tunnels
panels) have not allowed a formal diagnosis. Muscle MRI can allowing one of the parents to lie next to the child during
help guide further paraclinical investigations, for example the examination. The use of general anesthesia should be
by identifying muscle groups with inflammatory changes for avoided. In case of myopathic patients suffering from
which muscle biopsy is most likely to be cost-effective (or, respiratory insufficiency, the imaging team must work in
similarly to what has been described above, by identifying a collaboration with the anesthesia-intensive care team to
characteristic pattern of muscle damage that could redirect ensure that the examination is carried out in a safe
the genetic panels to be performed in order to reach a formal environment (non-magnetic monitoring and assisted ventila-
diagnosis); tion equipment, continuous medical surveillance).
 when the genetic analyses have revealed a variant of
undetermined significance, access to the evaluation of deep 2.2.2. Equipment
muscle groups (clinically non-assessable) allowing the Both 1.5T and 3T magnetic fields can be used, with the
identification of clinically silent disorders can establish advantage of a 3T MR system being to reduce acquisition time
the diagnosis and direct toward proper management and due to a larger signal reserve. For older equipment, a whole-
early follow-up; body antenna can be integrated into the machine; for newer
 quite similarly, when the clinical diagnosis of myopathy is machines, coupling head/neck, lower limb and posterior
not clearly established (subtle clinical lesions, normal antennas/surface antennas for trunk exploration is preferred.
routine paraclinical examinations) or when an investigation
is carried out in asymptomatic relatives, the detection of 2.2.3. Acquisition technique [2,3]
clinically silent lesions can also help to correct the diagnosis. For muscle MRI, the field of exploration of must be wide,
allowing exploration starting from the temporal muscles and
2.1.2. Follow-up heading to the muscles of the forefoot distally including the
Whole-body muscle MRI allows a more precise quantification arms, forearms and hands.
than physical examination alone of the degree of muscle In order to achieve good analysis of the upper limbs, the
damage, by grading muscle fat infiltration, which is correla- operator must check that they are correctly positioned within
ted with the patient’s functional state and muscle strength. the field of exploration and the field of view (FOV) set for axial
Not only useful at the individual patient level, longitudinal slices that must be sufficiently wide (50–55 cm).
MRI monitoring of any myopathy also has an academic Spatial resolution must be sufficient to allow fine analysis
vocation, allowing a better understanding of their expression of each muscle group; therefore, joint sections with a
profile, and evaluating the effectiveness of available thera- thickness no greater than 5 mm should be acquired. The
pies. smaller the anatomical structure to be analyzed, the better
should be the spatial resolution (this is particularly true in the
2.1.3. Contraindications and alternatives analysis of the pediatric population).
Alternative imaging methods have been proposed in case of
contraindications for MRI (which are in practice rare and 2.2.4. Protocol
dominated by the presence of metallic foreign bodies or non- The protocol includes two types of sequences acquired in the
MRI-compatible medical devices, as well as severe respiratory axial plane, carried out successively, to be read in parallel
insufficiency or major claustrophobia). They are mainly (thus requiring, to be comparable and superimposable, the
represented by computed tomography (CT) and ultrasound. same acquisition parameters in terms of slice thickness and
The major disadvantage of CT is its irradiating nature, which acquisition plane):
should be avoided as much as possible in a population that is
often young and highly likely to be exposed to iterative CT  ‘‘anatomical’’ sequences to study muscle morphology,
scans in the context of the complications specific to their volume and the degree of fat replacement (typically T1-
disease. Ultrasound, which does not irradiate, is an easily weighted sequences);
accessible alternative with no contraindications for analysis of  ‘‘functional’’ sequences allowing the visualization of a
superficial muscle groups and for guidance of muscle biopsies possible increase in the quantity of water within a muscle;
but does not allow fine analysis of deeper muscle groups and is these are typically T2-weighted sequences with saturation
operator dependent. of the fat signal (using the Fat Sat or STIR method), that show
inflammation changes in the muscle.
2.2. How it is performed
These axial sequences are acquired in several stages, going
2.2.1. Examination environment from head to toe, that are then merged to allow optimal
The imaging team performing whole-body muscle MRI for the reading comfort. For the levels concerning the trunk (thorax
evaluation of inherited myopathies must be experienced in and abdomen), it is best to coordinate acquisition with
the management of these patients who are often severely breathing to reduce kinetic artefacts.
64 revue neurologique 179 (2023) 61–80

Fig. 3 – Four types of images acquired by Dixon method (Imaging Department, Raymond-Poincaré Hospital, Garches, AP–HP,
2022).

Nowadays, the Dixon method is widely used for acquisition character of the ‘‘anatomical’’ imaging and the imaging
instead of the traditional T1/T2 FS sequences. The Dixon objectifying the inflammation, since it is the same sequence.
method is a chemical shift-based method of fat and water A coronal plane should at best complete the examination if
separation; it is based on the fact that fat protons have a the patient’s tolerance is good, ideally acquired in three
different (and lower) resonance frequency than water protons dimensions, to allow multiplanar reconstructions in order to
(difference of 3.25 ppm or 208 Hertz at 1.5T): As the resonance restore symmetry, an essential condition for a rigorous
frequencies are shifted, the protons from these two tissues are analysis, when the positioning of the patient cannot be
periodically out of phase with each other over time (every optimal, to better assess spinal deformities and to allow better
2.4 ms at 1.5T). It is possible to acquire two images artificially visualization of certain muscle groups (masticators, tongue,
shifted by 2.4 mS, where in one series (‘‘in-phase’’) the water intercostals, psoas, long muscles of the extremities).
and fat protons are in-phase, and in the other series (‘‘anti- Under these conditions, the total examination time is
phase’’) the water and fat protons are out of phase and the fat between 30 and 45 minutes.
proton signal is not collected. By reconstruction using a simple Injection of gadolinium chelates is not recommended in
mathematical calculation, ‘‘Water’’ (showing only the signal clinical practice as it increases acquisition time and provides
from the water protons and thus ‘‘equivalent’’ to T2 STIR or Fat little additional information compared to inflammation-
Sat sequences) and ‘‘Fat’’ (showing only the signal from the fat sensitive sequences (apart from the analysis of enhancement
protons) images can be obtained. Thus, in a single acquisition, kinetics during dynamic gadolinium injection, which are
four complementary images are available (Fig. 3). sequences whose interpretation is not yet clearly established).
In current practice, a modern variant of the ‘‘two-point’’
Dixon method (described schematically above) called the 2.3. Interpretation
‘‘three-point Dixon method’’ and using an additional echo
time is preferred because of its more robust quantification of The interpretation of a whole-body muscle MRI in the context
intramuscular fat and water within a single pixel and its lesser of suspected myopathy must be orientated by the clinical and
sensitivity to magnetic field inhomogeneities. The Dixon paraclinical context provided by the referring clinicians and
method can be used with all possible ponderations (T1, T2 requires above all a detailed knowledge of the anatomy and
and DP). patterns of muscle damage, which may evolve with the
In the context of whole-body muscle MRI, T2-weighted progression of the disease.
Dixon sequences offer several advantages over conventional Several points need to be analyzed.
T1/TS FS or STIR sequences: overall reduced examination
time, homogeneous saturation of the fat signal even for large 2.3.1. Fat replacement of the muscle contingent
acquisition volumes (unlike ‘‘Fat Sat’’ methods), better signal- This is assessed on T1-weighted sequences or ‘‘FAT’’ imaging
to-noise ratio, the possibility of quantifying intramuscular fat of the T2 Dixon sequence if this method is preferred. Although
transformation and the obtention of strictly superimposable it is not specific (and can be encountered in various situations
 revue neurologique 179 (2023) 61–80 65

Fig. 4 – Example of Mercuri classification applied to the assessment of fatty degeneration for tongue muscles (Axial T2 ‘‘Fat’’
images, Imaging Department, Raymond-Poincaré Hospital, AP–HP 2019).

such as physiological aging, chronic treatment with corticos- assessment, in the absence of available reference threshold
teroids, denervation situations, etc.), it is an important process values; it is necessary to look for a disparity in volume between
to characterize in myopathies. The analysis must be carried a given muscle and the neighboring muscle groups. Muscle
out on the muscle group as a whole, and not just on a few atrophy most often accompanies fat replacement of the
sections, on the most suitable analysis plane. Healthy muscle muscle body but may rarely be the only abnormality noted
tissue normally appears hypointense, while fat replacement is on examination, particularly in young children with conge-
hyperintense; this process is often associated after a certain nital muscular dystrophy in whom the intramuscular fatty
period of time with replacement by connective tissue (also infiltration may be very modest and sit inter- muscularly.
hypointense and most often consisting of a thickening of the Adaptive (reactionary) hypertrophy of the muscles adjacent to
fibrous trabeculae and physiological facias) reflecting irrever- the pathological muscles may also be noted, in compensation
sible damage. To allow a more reproducible semi-quantitative for the induced deficit or in the case of an inflammatory
scoring, it is customary to use the Mercuri classification process (myositis). Eventually, the increase in muscle volume
(derived from the Goutallier and Bernageau classification used due to fatty infiltration is called pseudohypertrophy.
to score fatty replacement of rotator cuff muscles in the
shoulder, and proposed in 2002 initially in patients with stiff 2.3.3. Existence of a specific pattern of damage to a given
spine syndrome) in four stages (Fig. 4) [4]: muscle group
For example, the preservation of central muscle fascia on
 stage 1: normal; either side of significant fat replacement (centripetal involve-
 stage 2: less than 30% fat replacement; ment) may give the muscle a ‘‘tigroid’’ appearance characte-
 stage 3: estimated fat replacement between 30% and 60%; ristic of collagen 6-related myopathies.
 stage 4: fat replacement greater than 60%.
2.3.4. Existence of a pathological increase in the quantity of
2.3.2. Muscle group trophicity water within a muscle
Muscle trophicity is best assessed on T1-weighted sequences This is demonstrated by a hyperintensity on T2 STIR/FS/Dixon
or ‘‘FAT’’ images of the Dixon T2 sequence. It is a qualitative ‘‘Water’’ sequences. This hyperintensity is not specific but
66 revue neurologique 179 (2023) 61–80

may reflect the early and active nature of certain myopathies, concerning the small and medium gluteal muscles as well as
preceding the occurrence of fatty changes by a few weeks: this the large adductors, followed by the iliopsoas muscles, in an
is particularly true for DM1, FSH, the early phase of DMD and earlier and more severe manner, the gluteus maximus
certain metabolic myopathies but also for most acquired muscles and the quadriceps, certain hamstrings (biceps
myopathies. It may also be caused by denervation. femoris and semitendinosus) and the muscles of the posterior
calf lodges explaining the pseudohypertrophy noted clinically
2.3.5. Distribution and symmetrical nature of the damage (soleus, lateral and medial gastrocnemius, fibular). The
A possible gradient of involvement (proximal/distal, anterior/ internal and external obturators, long adductors, semimem-
posterior or lateral/medial) may help to orientate towards a branosus, gracilis and sartorius muscles are preserved (Fig. 5)
subtype or type of pathology, even though there are few [7].
pathologies that exhibit sufficient correlation between imag- 2.4.1.1.2. Becker myopathy. Less severe clinical involve-
ing data and clinical/biological data. It is also necessary to ment. On imaging [7], the damage is proximal and symme-
specify whether there are selective atrophies (as in selenopa- trical, preferentially affecting the gluteal muscles, the
thies where there may be selective atrophy of the semimem- semimembranosus muscles and the quadriceps. Pseudohy-
branosus muscle) or, on the contrary, selective hypertrophies. pertrophy of the calves is also classically found. The upper
Similarly, the symmetrical or asymmetrical nature of the limbs are usually spared; if there is any involvement, it is more
involvement can help to propose a restricted diagnostic range: likely to be of the biceps, triceps and round muscle. In this
certain pathologies classically give an asymmetrical involve- case, muscle MRI is sometimes diagnostic of a ‘‘pseudo-
ment well documented in the literature, such as FSHD and LGMD’’ presentation.
certain limb-girdle myopathies.
Algorithms to orientate the diagnosis hypotheses have 2.4.1.2. Myotonic dystrophies (MD). This group includes two
been published in the literature; they integrate all these data genetically distinct conditions: myotonic dystrophy type 1
and make it possible to propose a more restricted diagnostic (DM1, also known as Steinert’s disease) and myotonic
range [5,6]; these decision trees are, however, more precise for dystrophy type 2 (DM2, also known as PROMM for proximal
lower limb involvement. A study to be published conducted in myotonic myopathy). These two multi-systemic disorders are
our institution shows that paraspinal muscle involvement both autosomal dominants, and have three cardinal clinical
patterns can also help distinguish among inherited myopa- signs in common:
thies.
 myotonia, i.e., abnormal slowness of muscle relaxation,
2.3.6. Other elements clinically manifested by the persistence of a strong muscle
The impact on the musculoskeletal system must be noted in contraction after percussion of the muscle and leading to an
order to adapt management (severe osteoarthritis or ankylosis unpleasant but non-painful sensation of stiffness for the
due to immobility of the joint segments concerned). patient;
Associated disorders must be noted: the existence of  muscle weakness;
inflammatory changes in the soft tissues is important to note  early cataract.
in the context of acquired myopathies (which may indicate for
instance a dermatitis associated with a possible polymyositis). 2.4.1.2.1. Type 1 MD. Whole-body MRI shows [8,9] skeletal
The evaluation of brain sections is also important to detect muscle damage, predominantly distal, associating fatty
white matter abnormalities (allowing specific orientation involution, atrophy and sometimes inflammatory T2 hyper-
towards certain inherited myopathies such as LAMA2). signal of the affected muscle bodies. In the lower limbs, the leg
is usually more severely affected than the thigh; the anterior
2.4. Key patterns in major myopathies compartments are more affected than the posterior compart-
ments. The pelvic girdle and the posterior tibial, gracilis and
2.4.1. Inherited myopathies rectus femoris muscles are usually preserved. In the upper
2.4.1.1. Dystrophinopathies. Dystrophinopathies are a group limbs, preservation of the muscles of the shoulder girdle is the
of muscular dystrophies caused by an X-linked mutation rule. Moderate involvement of the forearm muscles may be
inducing an absence, insufficient production, or dysfunction seen. In the face and neck muscles: the sternocleidomastoid,
of dystrophin, a key protein ensuring the strength of muscle masticatory muscles and muscles of the face are affected.
fibers by allowing actin filaments (intracellular contractile Concerning the trunk: damage to the diaphragm is responsible
apparatus) to bind to the structural proteins of the extra- for respiratory complications. Involvement of the erector
cellular membrane. This group includes two main clinical spinae muscles may be noted, generally of moderate severity.
entities according to disease severity, which is correlated with 2.4.1.2.2. Type 2 MD. Whole-body MRI shows [8,9] pre-
the amount of functional dystrophin. dominantly proximal skeletal muscle damage with fatty
2.4.1.1.1. Duchenne myopathy. Most severe clinical pre- involution and atrophy less marked than in type 1 MD. There
sentation. Whole-body muscle MRI is of limited use in the is marked involvement of the paravertebral muscles (parti-
initial assessment because the clinical phenotype is sugges- cularly at the cervical level) and the gluteus maximus, as well
tive. However, it is useful for monitoring disease progression as the scapular and pelvic girdles. In general, there is no T2
and adapting the treatment if needed. MRI findings are hypersignal inflammation. In contrast to type 1 MD, the
consistent with the clinically observed impairment, showing muscles of the face are spared and there is no involvement of
symmetrical damage in a preferential proximal topography the masticatory muscles or esophageal dilatation.
 revue neurologique 179 (2023) 61–80 67

Fig. 5 – Whole-body muscle MRI in a patient with Duchenne dystrophy (Axial T2 Dixon ‘‘Fat’’ and ‘‘Water’’ images; Imaging
Department, Raymond-Poincaré Hospital, AP–HP 2022). Note the symmetrical muscle damage, of proximal predominance.
The muscle damage concerns mostly the pelvic girdle (particularly gluteus muscles), the quadriceps, the hamstrings (biceps
femoris and semitendinosus) and the muscles of the posterior calf lodges (soleus, lateral and medial gastrocnemius but
also the fibular) showing the classical ‘‘pseudohypertrophy’’ noted clinically. The scapular girdle and the axial paraspinal
muscles are mildly affected. T2 hypersignal may be found in the active phase of the disease. The internal and external
obturators, long adductors, gracilis and sartorius muscles are preserved.

2.4.1.3. Limb-girdle muscular dystrophies (LGMD). Limb-girdle posterior thigh, then the adductor magnus and vastus
muscular dystrophies are genetic diseases that have in intermedius muscles. Leg involvement is predominantly in
common the preferential clinical involvement of the muscles the medial gastrocnemius and soleus muscles. Involvement of
of the pelvic girdle (the most frequently affected) and the the shoulder girdle is manifested by detachment of the
scapular girdle. This category includes several clinical entities scapulae and occurs after involvement of the pelvic girdle.
that meet several common diagnostic criteria. The currently The spinal erectors tend to be affected laterally in the extensor
used classification of LGMD was established by a group of group (longissimus and ilio-costal muscles) compared to the
international experts at the 229th European Neuromuscular medial rotator muscles (multifidus and rotators). A ‘‘pseudo
Centre (ENMC) international workshop held on 17–19 March collagen’’ pattern of involvement can be seen (central sparing
2017 [10]. It is based on: zones in certain muscles) and is predictive of a longer and
more severe disease course.
 the mode of transmission: dominant (LGMD D) or recessive 2.4.1.3.2. LGMDR9 linked to fukutin related protein (FKRP)
(LGMD R); gene. Whole-body muscle MRI shows (Fig. 7) [13,14] predomi-
 a numbering system corresponding to the chronological nant involvement of the muscles of the posterior thigh and
order of description of the entity; often signs of hypertrophy of the gracilis muscle. In the leg,
 the citation of the protein involved in the physiopathology of there is diffuse involvement of all muscles, with the medial
the entity. gastrocnemius being more affected than the lateral, and
marked involvement of the fibular and tibialis anterior
Thus, for example, we will speak of LGMD R1 linked to calpain muscles.
(of recessive transmission ‘‘R’’, described first among the 2.4.1.3.3. LGMDR2 linked to dysferlin. Whole-body muscle
LGMDs, hence the number ‘‘1’’ and ‘‘linked to calpain-3’’) MRI shows (Fig. 8) [15–17] severe involvement of the anterior
instead of LGMD2A in the old classification, which was less and posterior thigh compartments with sparing of the
explicit and based essentially on the recessive or dominant sartorius and gracilis muscle. Early leg involvement is
character and on the chronological order of description. predominantly in the posterior compartment and initially
2.4.1.3.1. LGMDR1 linked to calpain. Whole-body muscle spares the medial gastrocnemius muscle; the posterior tibial
MRI shows (Fig. 6) [11,12] in particular the involvement of the muscle is preserved. However, a recent series suggests that
68 revue neurologique 179 (2023) 61–80

Fig. 6 – Whole-body muscle MRI in a patient with LGMDR1 linked to calpain (Axial T2 Dixon ‘‘Fat’’ images, Imaging
Department, Raymond-Poincaré Hospital, AP–HP 2021). Note the symmetrical damage of the scapular girdle (especially
trapezius and subscapularis muscles) and more severely the pelvic girdle (gluteus and adductor longus and brevis muscles
mostly in this patient); the spinal damage is preponderant on extensor (lateral) muscles compared to rotator (medial)
muscles. In the lower limbs, the involvement is marked in the posterior thigh (almost fully fatty) and extends anteriorly
towards the quadriceps, especially the vastus intermedius and lateral muscles; note the presence of a ‘‘pseudo collagen’’
pattern of involvement (fatty infiltration sparing the central part of the muscle, see red arrow). Leg involvement concerns
mostly the gastrocnemius and soleus muscles, with sparing of the anterior compartment.

Fig. 7 – Whole-body muscle MRI in a patient with LGMDR9 linked to FKRP (Axial T1 images, Imaging Department, Raymond-
Poincaré Hospital, AP–HP 2018). Note the symmetrical pattern of muscle fatty infiltration, affecting the scapular and pelvic
girdles as well as the spinal muscles. In the thighs, both anterior and posterior compartments are involved; note the sparing
(with relative hypertrophy) of the gracilis. In the legs, there is diffuse involvement of all muscles, with the medial gastrocnemius
being slightly more affected than the lateral, and marked involvement of the fibular and tibialis anterior muscles.
 revue neurologique 179 (2023) 61–80 69

Fig. 8 – Whole-body muscle MRI in a patient with LGMDR2 linked to dysferlin (Axial T2 Dixon ‘‘Fat’’ images, Imaging
Department, Raymond-Poincaré Hospital, AP–HP 2018). Whole-body muscle MRI shows involvement of the anterior and
posterior thigh compartments with sparing of the sartorius and gracilis muscle. The scapular and pelvic girdles and the
spinal muscles are also affected.

involvement of the medial gastrocnemius (later) as well as the and rectus anterior muscles and moderate damage to the axial
soleus is suggestive of dysferlinopathy independently of the musculature, while the adductors and muscles of the posterior
clinical phenotype. Cardiomyopathy and respiratory involve- thigh (particularly the semitendinosus) are involved early,
ment are possible. A distal predominant pattern (called followed by the vastus muscles. In the leg, the medial
‘‘Miyoshi distal myopathy’’) is another possible presentation gastrocnemius and soleus muscles are involved at an early
of the same myopathy. stage, followed by the lateral gastrocnemius, fibular and
2.4.1.3.4. Sarcoglycanopathies. This group consists in many tibialis anterior. An increase in water volume within the
genetical and clinical entities [LGMDR3 related to a-sarcoglycan, involved muscle groups may precede atrophy.
the most common; LGMDR5 related to g-sarcoglycan, LGMDR4
related to b-sarcoglycan and LGMDR6 related to d-sarcoglycan 2.4.1.4. Titinopathies. Titinopathies are a group of diseases
(ex LGMD2C, D, E, F)] that are clinically similar, with onset of caused by mutations in the TTN gene encoding titin, located on
symptoms occurring at a variable age, mostly in childhood. chromosome 2. Titinopathies are inherited in an autosomal
Whole-body muscle MRI shows (Fig. 9) [15,18] involvement of dominant or, more rarely, autosomal recessive manner. The
the anterior thigh compartment (mainly the vastus interme- clinical pictures generated are very varied, from a simple
dius). Leg involvement is predominantly in the fibular and muscular discomfort with little or no progression to dramatic
soleus muscles. Hypertrophy of the gracilis and sartorius pictures with premature death in the child. Several clinical
muscles and sometimes of the semitendinosus can be observed. forms can be distinguished according to the onset of the
2.4.1.3.5. LGMD R12 linked to anoctamin 5. Whole-body symptoms, the most frequent being the Emery-Dreifuss-like
muscle MRI classically shows (Fig. 10) [19,20] an initial myopathy. Whole-body MRI shows few specific patterns for
preservation of the gluteal, psoas, iliac, sartorius, gracilis other entities [21–23].
70 revue neurologique 179 (2023) 61–80

Fig. 9 – Whole-body muscle MRI in a patient with LGMDR3 related to a-sarcoglycan (Axial T2 Dixon ‘‘Fat’’ images, Imaging
Department, Raymond-Poincaré Hospital, AP–HP 2018). Note the involvement of the scapular and pelvic girdles as well as
the spinal muscles. In the thighs, the damage begins with the anterior compartment (mainly the vastus intermedius) and
progress to the posterior compartment with severe fatty infiltration of the hamstrings; the sartorius and gracilis muscles
are spared. Leg involvement is predominantly in the soleus and, to a lesser extent, fibular muscles with sparing of the
gastrocnemius.

2.4.1.5. Laminopathies. The most common entity of this group posterior leg. At a later stage, there is involvement of the
of diseases, is type 2 autosomic-dominant Emery-Dreifuss thighs with predominant involvement of the gracilis, sartorius
myopathy, characterized by slowly progressive muscle weak- and semitendinosus as well as involvement of the shoulder
ness and atrophy (humeroperoneal then more diffuse), tendon muscles.
retractions beginning in early childhood and later cardiac 2.4.1.6.2. Zaspopathies. They are the second most
involvement, generally after the second decade, characterized common cause of MMF in France. The classic clinical
by conductive and rhythmic disorders and dilated cardio- presentation of zaspopathy is a late-onset distal myopathy
myopathy. Muscle imaging may show isolated involvement of (about 45 years of age) slowly progressing with involvement
the medial gastrocnemius, which is suggestive in the early of the intrinsic extensor muscles of the hand and wrist and
stages of the disease [24]. then the proximal muscles of the limbs and trunk. Muscle
imaging shows [26,27] predominant involvement of the
2.4.1.6. Myofibrillar myopathies (MMF). This group of dystro- muscles of the posterior compartment of the calf with early
phies is genetically heterogeneous and includes multiple degenerative changes in the medial gastrocnemius and
entities with the involvement of the loss of function of six soleus; in the thigh, the posterior compartment (biceps
main genes; however, they share a common point in their femoris and semimembranosus) is predominantly involved
histological analysis: the intracellular accumulation of pro- while the semitendinosus, adductor magnus and gracilis are
teins originating for the most part from the Z-stripe and whose relatively unaffected.
early disorganization is visible by electron microscopy. 2.4.1.6.3. Alpha-crystallinopathies. The phenotype is cha-
Whole-body muscle MRI shows some specific findings for racterized by onset in adulthood (30–40 years) of progressive
some entities [25]. muscle weakness affecting both proximal (most upper limb)
2.4.1.6.1. Desminopathies. They are the most frequent and distal (most lower limb) muscles. It is associated with
forms of MMF in France. On whole-body MRI, there is usually respiratory failure (which can be severe), hypertrophic
early fatty degeneration of the leg muscles, particularly in the cardiomyopathy and cataracts, with phenotypic variability
long fibular, then the tibialis anterior and the muscles of the within and between families. Based on the few cases reported,
 revue neurologique 179 (2023) 61–80 71

Fig. 10 – Whole-body muscle MRI in a patient with LGMDR12 linked to anoctamin 5 (Axial T2 Dixon ‘‘Fat’’ images, Imaging
Department, Raymond-Poincaré Hospital, AP–HP 2019). Note the relatively moderate damage of the gluteal, psoas, axial
musculature (except for the lumbar level) and shoulder girdle compared to the severe damage of the posterior
compartments of the thighs; the anterior compartments of the thighs is less severely damaged too. In the leg, the
gastrocnemius are severely involved, followed by the soleus and the tibialis anterior muscles.

muscle MRI may show distal fatty infiltration of the tibialis semimembranosus, biceps femoris, adductor magnus, vastus
anterior and medial gastrocnemius muscles, and proximal intermedius and vastus medialis in the thigh, while the
involvement of the quadriceps, sartorius and tensor fascia lata sartorius, gracilis, and rectus femoris were relatively spared.
[28]. 2.4.1.6.6. Bag3opathies. The clinical picture is characteri-
2.4.1.6.4. Myotilinopathies. Muscle imaging shows [25] zed by severe muscle weakness of variable topography
mainly fatty involution in the distal muscles, initially in the (predominantly proximal, proximo-distal or distal), possibly
posterior leg compartment (particularly the soleus and medial associated with stiff spine syndrome. Cardiac and respiratory
gastrocnemius), and then in all other muscles including the involvement is common and can be very severe. Symptoms
tibialis anterior. When the thigh is involved, the pattern is less begin in the first decades of life. Muscle MRI does not show any
specific, with involvement of the semimembranosus, hip specific pattern of involvement.
adductors and biceps femoris.
2.4.1.6.5. C filaminopathies. Muscle MRI shows [29] pre- 2.4.1.7. Distal myopathy due to VCP (valosin containing protein)
dominant involvement of the soleus and medial gastrocne- gene mutation. The p97/VCP protein is an ATPase involved in
mius in the leg and fatty degeneration of the basal cell autophagy of cytosolic proteins ubiquitinated by the
72 revue neurologique 179 (2023) 61–80

Fig. 11 – Whole-body muscle MRI in a patient with VCP myopathy (Axial T2 Dixon ‘‘Fat’’ and ‘‘Water’’ images, coronal T1 and
frontal plain radiograph of the pelvis, Imaging Department, Raymond-Poincaré Hospital, AP–HP 2022). Note the
symmetrical involvement (blue arrows) of the axial paraspinal muscles (extensors more severely than rotators), the
shoulder girdle (trapezius, subscapularis), the deep common flexors of the fingers in the upper limbs and, in the lower
limbs, the quadriceps, the gastrocnemius medius and the anterolateral compartment of the leg. T2 hyperintensity are
noted in the paraspinal right muscle at lumbar level, the left vastus lateralis, the right lateral gastrocnemius and the left
anterior tibialis (yellow arrows). This patient also presented a bone involvement with Paget disease of the right ilium (red
arrows).

proteasome (Fig. 11). Its dysfunction (caused by genetic anterolateral compartment of the leg, as well as the deep
defects, more than 45 mutations having been described so common flexors of the fingers in the upper limbs (a distal
far) leads to an accumulation of ubiquitin and TDP-43 positive predominance as classically been described, although proxi-
protein clusters in vacuoles, called ‘‘inclusion bodies’’, in mal predominance can be found). As in facioscapulohumeral
muscle cells, osteoclasts and neurons, hence the name muscular dystrophy (FSH) (see below), the ‘‘scapula alata’’ sign
‘‘IBMPFD’’ for inclusion body myopathy, Paget and fronto- can be found but facial muscle involvement is generally
temporal dementia. The muscular manifestations are the milder. T2 hypersignals in muscles involved (especially in the
most frequent symptoms (affecting 90% of individuals, with lower limbs) is frequently noted and precedes the installation
adult onset), followed by the bone disease (Paget disease, in of fatty degeneration.
40% of individuals) and the cognitive impairment (fronto-
temporal dementia in 30% of individuals, but also less 2.4.1.8. Facioscapulohumeral muscular dystrophy (FSH). FSH
frequently other types of dementia such as amyotrophic is one of the most common muscular dystrophies in adults.
lateral sclerosis, Parkinson and Alzheimer’s diseases). Whole- Two genetic subtypes have been described. Whole-body
body muscle MRI classically shows [30,31] a symmetrical muscle MRI (Fig. 12) [3,32] is of a particularly contributive for
involvement of the axial paraspinal muscles (mostly concern- the initial diagnosis and shows data that is consistent with
ing the extensors rather than the rotators), the quadriceps, the the clinical damage described, i.e. motor deficit and hypo-
 revue neurologique 179 (2023) 61–80 73

Fig. 12 – Whole-body muscle MRI in a patient with FSH dystrophy (Axial T2 Dixon ‘‘Fat’’ and ‘‘Water’’ images, Imaging
Department, Raymond-Poincaré Hospital, AP–HP 2020). Note the asymmetrical pattern of fatty infiltration, concerning the
facial muscles, the shoulder girdle (with damage predominating in the trapezius, serratus major, pectoralis major and
dorsalis major with sparing of the rotator cuff and deltoid muscles), the axial muscles, the abdominal and pelvic girdle with
the gluteus (severe involvement of the right side and almost complete sparing of the left side), the lower limbs with severe
damage to the right adductors (marked for the adductor longus), the hamstrings, the right anterior tibialis and the left
fibular muscle. Sparing of the vastus in the thighs and the posterior compartments of the legs is classically noted for a long
time (as present in this patient). T2 hyperintensity in muscles are noted (white arrows, concerning the right biceps femoris,
the left gracilis and the right lateral gastrocnemius).

trophy of asymmetric distribution, beginning with the facial gical increase in muscle water content is more intense in
muscles (difficulty in smiling, whistling, closing the eyes, type 2 FSH compared to type 1.
with no swallowing disorders) and the muscles of the
shoulder girdle (resulting in a suggestive symptom on 2.4.1.9. Congenital muscular dystrophies. Congenital muscu-
clinical examination: detachment of the spinal edge and lar dystrophies (CMDs) constitute a heterogeneous group of
the tip of the scapula during antepulsion and abduction of pathologies (on a clinical and genetic level) characterized by
the arm, also known as ‘‘scapula alata’’). The trapezius, symptoms associating with varying degrees muscular weak-
serratus major, pectoralis major and dorsalis major muscles ness, amyotrophy, hypotonia, contractures or psychomotor
are affected more than the rotator cuff and deltoid muscles, retardation, the onset of which is early (from birth or during
which are preserved. The muscles of the forearm are also the first months of life). Within CMD, three major subgroups
affected in the state phase. In the lower limbs, the damage are distinguished according to the cellular level affected by the
starts with the adductors, hamstrings, rectus femoris, responsible mutation to which is added a group whose
medial gastrocnemius and tibialis anterior, while the vastus responsible mutations are not yet identified.
thigh, lateral and posterior leg muscles are preserved for a Whole-body muscle MRI can have a major impact on the
long time. Involvement of the abdominal girdle muscles and orientation and prioritization of the genetic analyses carried
the erector spinae muscles is frequently described, while the out, finding highly suggestive or even characteristic disorders
iliopsoas muscles are preserved. In addition to the asymme- in three CMDs.
trically distributed muscle damage, predominantly facial 2.4.1.9.1. CMD with primary merosin deficiency. Skeletal
and scapular, described above, it can frequently show a muscle involvement is most common in the adductor magnus,
pathological increase in the volume of intramuscular water posterior thigh muscles and soleus muscles; the small and
within the affected muscle groups (particularly in the early medium gluteal muscles and the subscapular muscles may
phase), very suggestive of the diagnosis. It has been also be affected (Fig. 13). The sternocleidomastoid muscles are
described that the lower limbs are more severely and usually respected. Abnormalities of the cerebral white matter
frequently affected than the upper limbs, and the patholo- that may be associated should be detected on this examina-
74 revue neurologique 179 (2023) 61–80

Fig. 13 – Whole-body muscle MRI in a patient with CMD with primary merosin deficiency (Axial T2 Dixon ‘‘Fat’’ and ‘‘Water’’
images, Imaging Department, Raymond-Poincaré Hospital, AP–HP 2016 for the yellow box and 2020 for the other images).
Note the symmetrical damage concerning the subscapular muscles, the spinal muscles, the adductors, the anterior and
posterior thigh muscles and the posterior leg compartment, more severe than the MRI realised 4 years before (yellow box)
where T2 hyperintensities were noted. Also note the cerebral involvement with presence of T2 hypersignals in the
periventricular and subcortical white matter.

tion, as they greatly orient the diagnosis when they are to help distinguish them), and severe ventilatory impairment
present; it consists in characteristic often asymptomatic T2 often requiring recourse to permanent mechanical ventilation
hypersignals in the periventricular and subcortical white before adulthood. Peripheral skeletal muscle damage is
matter; more rarely, polymicrogyria or focal cortical dysplasia preferentially and early on in the disease, involving the
preferentially in the occipital lobe may be found. semimembranosus muscle (with relative respect for the other
2.4.1.9.2. CMD with collagen VI impairment. This group muscle groups of the thigh and leg at the beginning of the
includes two entities: Ullrich-type CMD, a severe form, and disease) and the lateral and medial gastrocnemius muscles
Bethlem-type CMD, a more moderate form (Fig. 14). The fatty (with sparing of the soleus and the tibialis anterior). As the
infiltration of the affected muscles follows a characteristic disease progresses, all the muscles of the thigh and leg may be
‘‘concentric’’ distribution, which is very useful for diagnosis, affected, with a predominant involvement of the anterior
starting at the periphery of the muscle and progressing compartment of the thigh compared to the posterior
centripetally. Skeletal muscle involvement is diffuse and compartment and the medial gastrocnemius muscle in the
tends to begin in the axial musculature. Subsequently, it will leg. Involvement of the sternocleidomastoid muscles is classic
concern in particular the sternocleidomastoid muscles, the and severe. The masticatory muscles are preserved. The
muscles of the shoulder girdle (in particular the subscapular gluteus maximus muscles may also be affected [4,6].
muscles), the upper limbs (in particular the triceps), the
gluteus maximus muscles and all the muscles of the thigh, 2.4.1.10. Congenital myopathies. Congenital myopathies are a
with the exception of the sartorius, gracilis and long adductor group of rare inherited myopathies comprising several entities
muscles, which are classically spared. defined based on characteristic lesions on muscle biopsy, e.g.,
2.4.1.9.3. CMD with selenoprotein deficiency. This entity is protein inclusions, alterations in internal fiber structure or an
also classified among the congenital myopathies (Fig. 15). It is increase in the number of centralized nuclei. Symptom onset
characterized clinically by a stiff spine syndrome caused by is generally in the ante- or peri-natal period, but there are
severe damage of the axial musculature (a syndrome shared exceptions. More than thirty genes have been implicated in
by many congenital myopathies and dystrophies, which is the the pathogenesis of congenital myopathies; the mutations
reason why an algorithm has been described in the literature involved are of variable transmission (X-linked, autosomal
 revue neurologique 179 (2023) 61–80 75

Fig. 14 – Whole-body muscle MRI in a patient with CMD with collagen VI impairment (Ullrich-type) (Axial T2 Dixon ‘‘Fat’’
images, Imaging Department, Raymond-Poincaré Hospital, AP–HP). Note (red arrows) the characteristic ‘‘concentric’’
distribution of the fatty degeneration for a given muscle (starting at the periphery of the muscle and progressing
centripetally), very suggestive of this disease. Skeletal muscle involvement is diffuse, symmetrical, and concerns the axial
musculature (rotator and extensor spinal muscles being equally involved), the sternocleidomastoid muscle, the
subscapular and deltoid muscles for the shoulder girdle, the upper limbs and particularly the triceps, the abdominal girdle,
and all the muscles of the thighs except for the gracilis, the sartorius and the long adductor muscles. Leg involvement is
mild in this case and concerns the fibulars.

recessive or dominant). There are three main groups of more discreetly the masticatory muscles (lateral and medial
congenital myopathies, according to the type of muscle fiber pterygoid muscles, temporals, masseters). The sternocleido-
abnormality found under the microscope. mastoid muscles are also spared [33].
2.4.1.10.1. Myopathies with cores. Characterized by the 2.4.1.10.2. Myopathies with central nuclei. Myopathies with
presence of abnormal areas called ‘‘cores’’ within the muscle central nuclei are characterized by an unusual location of the
fibers, including two entities. nuclei in the center of the muscle fibers. There are two entities.
Myopathy with multi-minicores: same clinical and genetical Centronuclear myopathy: there are two forms: an autosomal
entity as CMD with selenoprotein deficiency discussed above. dominant form (the most frequent) by mutation of the DNM2
Myopathy with central cores: also called RYR 1 myopathy gene encoding dynamin 2 and an autosomal recessive form
(named after the gene responsible for the disease). Symptoms linked to a mutation of the BIN1 gene encoding amphiphysin 2,
usually develop in childhood but may develop at adult age. It is which is very rare. In the DNM2 form, whole- body muscle MRI
characterized by delayed motor development and signs of shows thigh damage, which is moderate and affects the
mild proximal weakness most pronounced in the pelvic girdle gluteus minimus, adductor longus and vastus intermedius
and hip. Orthopedic complications, in particular congenital muscles, and severe damage to the hamstrings (semitendi-
hip dislocation and scoliosis, are common. A specific pattern nosus), while the vastus medialis and lateralis, sartorius and
of MRI involvement of the thighs has been described (Fig. 16), gracilis muscles are relatively unaffected. In the legs, there is
with involvement of the gluteus maximus, adductor magnus, severe distal damage to the medial gastrocnemius and soleus
vastus lateralis and intermedius and sartorius muscles; the muscles. The posterior tibial muscle is spared. Concerning the
rectus femoris, adductor longus, gracilis and semitendinosus facial and ear-nose-throat muscles, in severe phenotypes the
muscles are spared. In the legs, there is almost selective temporal and lateral pterygoid muscles are affected, while the
involvement of the soleus muscles and, to a lesser extent, the masseter and medial pterygoid muscles are spared. T2 signal
fibulars. The posterior tibial, gastrocnemius and anterior tibial abnormalities of the paraspinal and extensor muscles of the
muscles are preserved. In the upper limbs, the biceps brachii, neck are possible. In the BIN1 form, which is not well described
subscapularis and paravertebral muscles are affected, and in imaging, MRI may show diffuse involvement of the thigh
76 revue neurologique 179 (2023) 61–80

Fig. 15 – Whole-body muscle MRI in a patient with CMD with selenoprotein deficiency (Axial T2 Dixon ‘‘Fat’’ images,
Imaging Department, Raymond-Poincaré Hospital, AP–HP, 2020). Note the severe scoliosis due to the damage of the axial
musculature (predominating in the rotator muscles), causing the stiff spine syndrome noticed by the clinical examination.
The sternocleidomastoid muscles are affected (which is a classical finding in this disease); The intercostal muscles are too.
In the lower limbs, the semimembranosus muscles are severely affected (almost absents) with relative respect of the other
muscles, especially the anterior compartment. The leg involvement begins with the gastrocnemius (with a mild fatty
degeneration being present in the right medial gastrocnemius for this patient), sparing the soleus and the tibialis anterior.

muscles without topographical predominance. In the legs, ment of the tibialis anterior (and to a lesser extent the
involvement is predominant in the medial gastrocnemius, soleus), while the gastrocnemius (especially the lateral) and
anterior tibial and fibular muscles, while the posterior tibial, fibularis are preserved. The thigh may not be affected (if
soleus and lateral gastrocnemius muscles are relatively affected, it predominates on the vastus intermedius and
spared. The biceps brachii is damaged. The muscles of the adductor magnus) [34]. Selective involvement of the lateral
face and the temporal muscles are spared. pterygoid (sometimes with tongue involvement) has been
Myotubular myopathy: in the thighs, the hamstring, adductor described [35];
magnus, vastus medialis and vastus intermedius muscles are  Nemalin-3 myopathy by mutation of the ACTA1 gene
severely affected. The rectus femoris, gracilis, sartorius, encoding actin: MRI shows diffuse, moderate involvement,
adductor longus and vastus lateralis muscles are spared. In predominantly of the sartorius and adductor magnus
the legs, MRI shows predominantly soleus muscle involve- muscles, while the gracilis and rectus muscles are usually
ment, while the medial gastrocnemius muscle is respected. spared. In the legs, the anterior tibial, fibular and posterior
2.4.1.10.3. Myopathies with protein accumulation. Myopa- tibial muscles are predominantly affected, while the soleus
thies with protein accumulation characterized by the abnor- muscle is less affected and the gastrocnemius muscles are
mal presence of protein clusters in the muscle fibers. There are spared;
two main classes.  Nemaline-4 myopathy by mutation of the TPM2 gene,
Rod myopathies (nemaline): this entity covers a wide spec- encoding beta-tropomyosin: Rarely described in imaging,
trum of congenital myopathies with the presence of nemaline the deficit is thought to concern more particularly the
bodies (rods) on muscle biopsy. About ten incriminating masticatory muscles (temporal and pterygoid), the leg
mutations have been described, of which three forms are the muscles (soleus and tibialis anterior); the rectus femoris,
most frequent: sartorius and gracilis muscles are relatively unaffected.

 Nemaline-2 myopathy by mutation of the gene coding for Myopathies with ‘‘cap’’ by accumulation of myosin storage: it is
nebulin (the most common): MRI shows predominantly due to a mutation in the MYH7 gene. On whole-body muscle
distal involvement with, in the leg, predominant involve- MRI, the tibialis anterior muscle is the earliest and most
 revue neurologique 179 (2023) 61–80 77

Fig. 16 – Whole-body muscle MRI in a patient with RYR 1 myopathy (central cores congenital myopathy) (Axial T2 Dixon
‘‘Fat’’ images, Imaging Department, Raymond-Poincaré Hospital, AP–HP, 2020). Note the symmetrical pattern of
involvement, concerning the masticatory muscles (lateral and medial pterygoid muscles, temporals, masseters), the spinal
muscles (mid involvement), the biceps brachii. The sternocleidomastoid muscles (not shown here) are spared. In the lower
limbs, note for the thighs the involvement of the gluteus, adductor magnus, vastus lateralis and intermedius and sartorius
muscles; the rectus femoris, adductor longus, gracilis and semitendinosus muscles are spared. In the legs, there is almost
selective involvement of the soleus muscles (mildly affected in this patient and mostly in the left side) and, to a lesser
extent, the fibulars. The posterior tibial, gastrocnemius and anterior tibial muscles are preserved.

severely affected, followed by the fibular, soleus and tibialis (tongue involvement is seen on MRI from the beginning of the
anterior muscles. In contrast, the lateral gastrocnemius is disease, even when it is subclinical), paravertebral muscles,
always spared. In the thigh, the vastus lateralis and abdominopelvic girdle, shoulder girdle (involvement of the
intermedius muscles are the most affected, while the rectus subscapularis and serratus major muscles in particular) and
femoris, adductor longus, sartorius and gracilis muscles are pelvic girdle (involvement of the adductor magnus muscle and
spared. of the glutei in particular). The thigh damage concerns mainly
the muscles of the posterior thigh, vastus intermedius, vastus
2.4.1.11. Metabolic myopathies: the glycogenoses. Glycogeno- lateralis and vastus medialis. The leg muscles are classically
ses are a group of diseases due to genetic abnormalities spared in this disease.
resulting in an alteration in the functioning of various key
enzymes involved in glycogenolysis or glycogenesis, resulting 2.4.2. Acquired myopathies
in an abnormal elevation of glycogen or the production of Given the frequently quite obvious context for toxic, endo-
structurally abnormal glycogen. Glycogen is essentially stored crine and infectious myopathies, the aim of imaging them is
in the liver and muscles, and a distinction is made between mainly to guide needle biopsies, for follow-up or academic
forms with predominantly hepatic expression, characterized purposes. For idiopathic inflammatory myopathies, whole-
by repeated hypoglycemia and severe liver damage (these are body muscle MRI may (although not frequently) help
glycogenoses type I, III, IV, VI, IX) and forms with a distinguish between clinical entities, as some patterns of
predominantly muscular expression producing a clinical damage have been described [39].
picture of myopathies (glycogenoses of type II, III, V, VII,
certain subtypes of IX, X, XIII, XIV, XV and 0). The most robust 2.4.2.1. Inclusion body myositis. It is the most common form
MRI pattern of damage has been described for type II of acquired myopathy in adults over 50 years of age. The
glycogenosis, also called Pompe disease (Fig. 17) [36–38], and disease manifests as a progressive (over years) loss of strength
consists in characteristic muscle involvement of the tongue and atrophy, affecting asymmetrically the quadriceps, the
78 revue neurologique 179 (2023) 61–80

Fig. 17 – Whole-body muscle MRI in a patient with Pompe disease (Type 2 glycogenosis myopathy) (Axial T2 Dixon ‘‘Fat’’
images, Imaging Department, Raymond-Poincaré Hospital, AP–HP, 2022). Note the characteristic severe muscle
involvement of the tongue (Mercuri 4, showing a totally fatty infiltration) but also the involvement of the shoulder girdle
(concerning mostly the subscapularis and serratus major muscles with sparing of the deltoids and the other muscles of the
rotator cuff), the paravertebral muscles, the abdominal and pelvic girdles (with involvement of the adductor magnus muscle
and of the glutei in particular). The thigh damage concerns mainly the muscles of the posterior thigh and the vastus
muscles. The leg muscles are spared (common finding in this disease).

finger flexors and foot extensors distally, the forearms, 2.4.2.3. Immune mediated necrotizing myopathy. This frequent
followed by involvement of the proximal muscles and of myopathy affects mostly adults and presents as an acute,
facial musculature with swallowing impairment. On MRI proximal and symmetrical muscle deficit. Except for cardiac
(Fig. 18), the fatty replacement is often significant (especially in involvement, there is traditionally no extra-muscular mani-
the quadriceps) and inflammation in muscle fasciae might be festations.
seen. On muscle biopsy there are abundant necrotic fibers
invaded or surrounded by macrophages and other regenerat-
2.4.2.2. Dermatomyositis. The clinical presentation consists ing basophilic fibers. Lymphocytic infiltrates are sparse. Anti-
in the association of skin involvement (which is frequent SRP and anti-HMGCoA reductase antibodies are specifically
and may be the only manifestation of the disease) and a found in autoimmune myositis. On whole-body MRI, muscle
proximal symmetrical myopathy of acute or subacute onset. inflammation is often extensive, especially in the lateral
The skin involvement may be seen in the MRI, as well as the rotators, gluteals, medial and posterior compartment of the
calcinosis that may complicate the disease. Regarding the thigh. Pronounced edema in the vastus lateralis while the
muscle involvement, MRI shows a symmetrical perifasci- vastus intermedius is relatively unaffected, may be suggestive
cular, perivascular and subcutaneous inflammation, as well of anti-SRP autoimmune necrotizing myositis rather than
as increase in intramuscular water volume on the T2 FS or other antibodies.
STIR sequence. Although muscle fibers undergo necrosis
and phagocytosis, there is little to no fat degeneration in 2.4.2.4. Anti-synthetase syndrome. Anti-synthetase syndrome
muscles. The upward progression involves the neck flexors is a systemic autoimmune disease associating pulmonary
and pharyngeal muscles, and the muscle edema most involvement, polyarthritis, fever, Raynaud’s phenomenon and
commonly involves the quadriceps, triceps and deltoids. In proximal and symmetrical subacute myopathic syndrome.
the thighs, the damage concerns the three compartments Numerous anti-synthetase antibodies have been described in
(unlike selective anterior compartment involvement for the literature, the most frequent being anti-Jo1, anti-PL-7, anti-
inclusion body myositis). PL-12, anti-OJ, anti-EJ, anti-KS, anti-Zo and anti-Ha.
 revue neurologique 179 (2023) 61–80 79

Fig. 18 – Whole-body muscle MRI in a patient with (Axial T2 Dixon ‘‘Fat’’ and ‘‘Water’’ images, Imaging Department,
Raymond-Poincaré Hospital, AP–HP, 2022). Note the asymmetrical involvement of the quadriceps (most severe and
common finding in this disease), the paraspinal muscles the forearms, the finger flexors and foot extensors distally. On
‘‘water’’ images, inflammation can be seen both in the muscle compartments affected and in the peri-muscular facias (red
arrows).

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