Fig. 12

Muscle imaging and light microscopy findings of genetically proven common neuromuscular genetic diseases: Steinert´s type 1 myotonic dystrophy (a, b, c, d, and e), Dystrophinopathy (f, g, h, i, and j), Facioscapulohumeral Muscular Dystrophy (k, l, m, n, and o), Spinal Muscular Atrophy (p, q, r, s, and t), Oculopharyngeal Muscular Dystrophy (u, v, w, x, and y), and Mitochondriopathy (z, α, β, γ, and δ). Muscle MRI of the pelvis (a), thighs (b), and legs (c) and muscle biopsy (d and e) of a 54 years old female patient with Steinert´s myotonic dystrophy type 1 confirmed by the detection of a EcoRI restriction fragment larger than 10Kb correspondent to expansion of the CTG triplet in the DMPK gene with muscle fat replacement of the vastus intermedius (green asterisk * in b), soleus (yellow asterisk * in c), and gastrocnemius medialis (red asterisk * in c), nuclear internalization (black arrow in d), and ring fibres (black arrow and green asterisk* in e) with areas of myofibrillar loss and disorganization in subsarcolemmal crescents characteristic of subsarcolemmal sarcoplasmic masses (yellow arrow in d and yellow asterisk * in e). Muscle MRI of the pelvis (f), thighs (g), and legs (h) of a 28 years old male patient, and muscle biopsy (i and j) of a 16 years old male patient, both patients with Dystrophinopathy subtype Becker muscular dystrophy related to a deletion in exons 45 to 47 of the DMD gene. Muscle imaging demonstrates the trefoil with single fruit sign (illustration in g, drawn based on the figure created and published by Zheng et al. 2015) characterized by muscle fat replacement of the thigh muscles with hypertrophy of the semitendinosus (orange asterisk * and single fruit in g), and three leafs represented by sartorius (green asterisk * and green leaf in g), gracilis (red asterisk * and green leaf in g), and adductor longus (yellow asterisk * and green leaf in g); muscle biopsy with necrosis and phagocytosis (yellow arrow in i), and decreased intensity in the immunohistochemical reaction for dystrophin (black arrow in j) compared to the dystrophin intensity in the control (green arrow in the inset in j). Muscle MRI of the pelvis (k), thighs (l), and legs (m) of a 42 years old male patient and muscle biopsy (n and o) of a 58 years old female patient, both patients with Facioscapulohumeral Muscular Dystrophy molecularly confirmed by EcoRI/AvrII restriction fragments smaller than 35 Kb in the D4Z4 locus inside 4q35; muscle imaging shows asymmetric muscle fat replacement that is more severe in right adductor magnus (green asterisk * in l) compared to the left adductor magnus (white asterisk * in l), decreased right calf volume with severe muscle fat involvement of the right soleus (yellow asterisk * in m) compared to the preserved left side (white asterisk * in m), involvement of the right gastrocnemius medialis (red asterisk * in m) compared to the preserved left side (green asterisk * in m), bilateral foot drop (not shown) was related to severe muscle fat involvement of the right tibialis anterior (green arrow in m), and left tibialis anterior (yellow arrow in m); muscle biopsy with nuclear clumps (yellow arrows in n and o), nuclear internalization (white arrow in n), and atrophic fibres with increased acid phosphatase reaction (white arrow in o). Muscle MRI of the pelvis (p), thighs (q), and legs (r) and muscle biopsy (s and t) of a 16 years old male patient with molecularly confirmed Spinal Muscular Atrophy with homozygous deletion of the exons 7 and 8 of the SMN1 gene, with the SMN2 gene presenting 4 copies of the exon 7 and 3 copies of the exon 8; muscle imaging shows atrophy of vastus intermedius (yellow asterisk * in q), vastus medialis (green asterisk * in q) and sartorius (white asterisk *in q) that presents an imaging pattern of decreased volume and muscle involvement by adipose tissue that has been described in neurogenic conditions (Astrea et al. 2022) and are useful for the differential diagnosis with muscular dystrophies (dystrophic processes usually present muscle fat replacement that preserves muscle volume, as observed in b, c, f, g, h, and l); muscle biopsy with groups of atrophic fibres (yellow arrow in s) and hypetrophic fibres (black arrow in s), with predominance of hypertrophic type 1 fibres (red asterisk * in t) with groups of atrophic type 2 fibres (green asterisk * in t). Muscle MRI of the pelvis (u), thighs (v), and legs (w) and muscle biopsy (x and y) of a 54 years old male patient with Oculopharyngeal muscular dystrophy molecularly confirmed by two alleles with 11 GCN (GA) repetitions in the PABPN1 gene (reference value below 10 GCN repetitions for the rare autosomal recessive presentation of this usually autosomal dominant disease); muscle imaging with muscle fat replacement of the adductor magnus (green asterisk * in v), and soleus (yellow asterisk * in w), muscle biopsy with rimmed vacuoles (yellow arrow in x), and 7.5 to 10 nm (mean outer diameter of 8.5 nm) nuclear inclusions disposed in tangles and palisades (yellow arrow in y). Muscle MRI of the pelvis (z), thighs (α), and legs (β) and muscle biopsy (γ and δ) of a 61 years old female patient with mitochondriopathy of the subtype Progressive External Ophthalmoplegia (PEO) molecularly confirmed by the a deletion in the mitochondrial DNA detected in muscle tissue with 46% of heteroplasmy in Southern blot and decreased enzymatic activity of the complexes I and IV of the mitochondrial respiratory chain in muscle biopsy tissue; muscle imaging demonstrated mild abnormalities in the gluteus minimus (green asterisk * in z), and sartorius (yellow asterisk * in α), muscle biopsy with ragged red equivalent/ ragged blue fibres (yellow arrows in γ and δ) characterized by subsarcolemmal and intermyofibrillary mitochondrial proliferation combined with a dissociated "ragged" appearance of the sarcoplasm that may be suspected by the amphophilic and basophilic granular subsarcolemmal depositis around the fibre and close to the basophilic nucleus on HE (γ), and later confirmed by histochemical oxidative studies such as SDH (δ), and COX (data not shown). Muscle imaging (a, b, c, f, g, h, k, l, m, p, q, r, u, v, w, z, α, and β) axial T1-weighted magnetic resonance imaging, yellow R: right side, yellow L: left side. Muscle biopsy (d, e, i, j, n, o, s, t, x, y, γ, and δ). d HE 200x, e Transmission Electron Microscopy 3,000x, i HE 200x, j, Immunohistochemistry antibody anti-dystrophin (N-terminus) NCL-DYS3 200x (patient) and inset (control), n HE 200x, o Acid phosphatase 200x, s HE 200x, t ATPase pH 9.4 50x, x HE 400x, y Transmission Electron Microscopy 20,000x, γ HE 400x, and δ SDH 100x)