Calf-Head Sign in Miyoshi Myopathy

ORIGINAL CONTRIBUTION Calf-Head Sign in Miyoshi Myopathy

Sunil Pradhan, MD, DM

Objective: To observe whether patients with Miyoshi- shoulders. T1-weighted magnetic resonance imaging of type dysferlinopathy demonstrate any distinct appear- the upper thorax and shoulder was performed in an ob- ance in the back of the shoulders and upper back in a lique sagittal plane to confirm the clinical findings. specific posture. Main Outcome Measure: Consistent pattern of muscle Design: Case series. enlargement or wasting seen clinically and at magnetic resonance imaging that produces a particular diagnos- Setting: Neurology outpatient clinic of a north Indian tic appearance. tertiary care medical institute. Results: A characteristic appearance was observed on Patients: Fifteen patients from 9 families (10 males and the upper back and shoulders that could be described as 5 females; age range, 16-42 years) who had Miyoshi my- calf heads on a trophy sign. The sign was clearly visible opathy with onset of calf and shin muscle wasting be- in 6 patients, whereas it was present in a subtle manner tween the ages of 9 and 28 years and a myopathic pat- in another 4. Some but not all components of the sign tern at electromyography, moderately high serum creatine were visible in the rest of the patients. kinase levels, and absence of dysferlin at immunohisto- chemical staining. Conclusion: The calf heads on a trophy sign may be use- Interventions: Patients were asked to raise their arms ful in identifying most patients with Miyoshi-type dys- with shoulders abducted and elbows flexed to 90°. All ferlinopathy. were observed from behind for the morphological change in the bulk of different muscles of the upper back and Arch Neurol. 2006;63:1414-1417

IYOSHI MYOPATHY (MM) computed tomography and magnetic reso- is an autosomal reces- nance imaging studies have been per- sive disease that was formed in distal limb muscles to show that first described in Ja- imaging abnormalities may precede clini- pan1,2 and subsequently cal symptoms.11,12 Sometimes, one part of a otherM countries. In this disease, muscular muscle is enlarged and another part wasted.13 wasting and weakness start from distal parts Subtle enlargement can be appreciated bet- of the lower extremities, particularly the ter when the muscle is under mild contrac- calves. Serum creatine kinase levels may be tion as happens when a particular posture moderately high. Results of recent studies is adopted.13 Making use of these phenom- suggest that MM and limb-girdle muscular ena, researchers have described particular dystrophy type 2B are allelic disorders; both appearances in different muscular dystro- diseases are linked to the same locus on phies, such as valley sign in Duchenne- chromosome 2p133-5 that includes the DYSF Becker muscular dystrophy,14,15 poly-hill sign gene encoding the protein dysferlin.6,7 Dys- in facioscapulohumeral dystrophy,16 and ferlin is a sarcolemma-bound protein8,9 in- shank sign in myotonic dystrophy.17 These volved in membrane repair.10 signs make use of the fact that some muscles Clinical diagnosis of MM is difficult in show relative enlargement or preserved bulk, the early stage despite advancement in de- whereas others show wasting in the same finitive diagnostic methods such as molecu- region. In this context, a particular appear- lar biology and muscle immunohistochem- ance in the upper back and the back of the istry. The reasons for the delay in diagnosis shoulders has been observed in MM-type could be the rarity of the disease and the on- dysferlinopathy. set from distal limb muscles. Muscular dys- trophies are known for the selective involve- REPORT OF CASES Author Affiliation: Department ment of skeletal muscles. This selectivity is of Neurology, Sanjay Gandhi not restricted only to weakness but ex- Postgraduate Institute of tends also to wasting and enlargement. The Fifteen patients from 9 families (10 males Medical Sciences, Lucknow, regional topography of involved muscles has and 5 females; age range, 16-42 years) with India. played a major role in early diagnosis, and MM-type dysferlinopathy who had onset

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©2006 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 of symptoms in the lower limbs between the ages of 9 and 28 years were selected for this study. The patients A were selected from a neurology outpatient clinic of a north Indian tertiary care medical institute (Sanjay Gandhi Post- graduate Institute of Medical Sciences). All patients had wasting of the calf muscles; 8 had remarkable wasting of the anterior leg (shin) muscles as well. They were ex- amined 3 to 11 years after the onset of symptoms, at a stage when they were independently walking but with difficulty in clearing the steps from the ground or get- ting up from a squatting position. There were no symptoms in the upper limbs in 7 patients, whereas the other 8 had mild generalized weakness in the arms, with sparing of the small muscles of the hand. At examination, 10 patients had mild wasting in the forearm muscles. The diagnosis of MM was based on gradual wasting of the leg B (calf/shin) muscles, moderately high serum creatine kinase levels, myopathic pattern at electromyography, and absence of dysferlin at immunostaining of muscle biopsy specimens. All patients were asked to raise their arms with shoulders abducted and elbows flexed to 90° as shown in Figure 1A. In this position, all patients were observed from behind for any specific appearance of the upper back and shoulders. This sign, which was described as calf heads on a trophy sign, diagrammatically shown in Figure 1B, was considered positive when 6 specific features were present. First is a prominent deltoid muscle looking like a calf’s head with the mouth at the muscle’s Figure 1. Calf heads on a trophy sign. A, Posture adopted to look for the calf heads on a trophy sign in a patient with Miyoshi myopathy. B, Diagrammatic insertion and one of the several linear depressions ap- representation matches with the actual sign shown in A. pearing like a half-closed eye; the prominence of the calf’s head was further enhanced at its lower border by slight wasting of the long head of the triceps muscle laterally per back because of the hollowing of the interscapular and the lateral part of the infraspinatus muscle medially region owing to wasting of the rhomboideus major and (the prominent posterior lower border of the deltoid overlying trapezius muscles. muscle sometimes created a double posterior axillary fold). The calf heads on a trophy sign was clearly visible Second is a cordlike upper border of the trapezius muscle (Figure 1A and Figure 2) in 6 patients, whereas it was appearing like a horn on the calf’s head; the horn stood present in a subtle manner in another 4, which included further prominent because of wasting of the supraspi- patients in both late and early stages of the disease. In natus muscle and the overlying trapezius muscle below the rest of the patients, some but not all components of it. Third is a prominent upper medial part of the infra- the sign were visible, and the overall appearance did not spinatus muscle with sharply demarcated wasting of the look like the calf’s head. The status of the individual com- lower and lateral part, looking like a downward di- ponents of this clinical sign is presented in the Table. rected ear of the calf. Fourth is the spinous process of Magnetic resonance imaging of the upper thorax and the scapula, which becomes prominent because of the left shoulder was performed with a 1.5-T superconduct- wasted supraspinatus above it appearing like the upper ing magnetic resonance imaging machine (LX Echo Speed border of the calf’s neck with its continuation medially Plus; General Electric Medical Systems, Milwaukee, Wis) as a subnuchal dorsal hump caused by the levator scapu- and a body coil. T1-weighted sagittal oblique imaging was lae and rhomboideus minor muscles, which show a lump- performed by using a spin-echo sequence with the fol- like prominence at their insertion over the upper me- lowing experimental parameters: relaxation time,500 mil- dial border of the scapula. Fifth is the ventral frill of the liseconds; echo time,15 milliseconds; number of exci- calf’s neck formed by enlarged latissimus dorsi and teres tations,4; and field of view,340 mm. Section thickness major muscles. Sixth is the overall appearance of the up- was 5 mm with no intersection gap and a 36 ϫ 12 ma- per back as that of a trophy with superolateral concave trix. The oblique sections were obtained at about a 40° arches formed by calf horns, upper lateral projections angle, starting from 5 cm medial to the medial border of formed by calf heads, and lower lateral convex arches the scapula and ending at the lateral border of the shoul- formed by the ventral frill of the calf’s neck. The inferior der. Four sections aptly described the status of the muscles border of the trophy is formed laterally by the promi- that were involved in the clinical sign; these passed nent upper borders of the latissimus dorsi muscles on through the oblique sagittal planes 3 cm medial and lat- either side and medially by the prominent lower bor- eral to the medial angle of the scapula and 3 cm medial ders of the trapezius muscles, which meet each other me- and lateral to the acromioclavicular joint (Figure 2). Skin dially. These calf heads appeared prominent over the up- over the bulky deltoid muscle showed depression at those

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©2006 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 Table. Frequency of Morphological Features That Represent Individual Components of the Calf Heads on a Trophy Sign

Morphological Feature Gross Mild Absent Hypertrophy of the deltoid muscle 2 13 0 Longitudinal serrations in the deltoid muscle 8 4 3 Wasting of muscles bordering the deltoid 3102 muscle (biceps, triceps, lateral part of infraspinatus, trapezius), rendering deltoid bulge out as calf’s head Cordlike superolateral border of the trapezius 10 2 3 muscle (looking like a calf’s horn) Wasting of the supraspinatus and overlying 843 trapezius muscles, giving prominence to the calf’s horn Enlargement of the medial part of the 663 A B C D infraspinatus muscle with sharp demarcation from the wasted lateral part (mimicking the calf’s ear) A Levator Scapulae Muscles Bulge due to slight enlargement or preserved 537 bulk of the muscle fibers near the insertion of the levator scapulae muscles over the Thinned Out Trapezius Muscle With superomedial border of the scapula Prominence at the Lower End Thinned out interscapular portion of the 942 trapezius muscle Prominent lower border of the trapezius 375 muscle Atrophic Rhomboideus Major Muscle Enlargement of the teres major and latissimus 555 dorsi muscles at the medial lower part of the posterior axillary fold (simulating ventral skin fold of the calf’s neck) B Hypertrophic Upper End of the Trapezius Muscle With Excessive Fibrosis Within

Thinned Out Trapezius Muscle

Wasted Supraspinatus Muscle places where fascia separating the muscle fiber bundles

Spinous Process of the Scapula reached up to the periphery. Muscle fibers at the superior- most level of the trapezius muscle showed tubular en- Scapula largement that appeared circular in cross section; imme- Preserved Infraspinatus Muscle diately below, the trapezius muscle showed wasting over Latissimus Dorsi Muscle the wasted and fibrosed supraspinatus muscle. The lower border of the trapezius muscle also showed slight en-

C Cross Section of Cordlike Upper Border largement, but the rhomboideus major muscle showed of the Trapezius Muscle wasting. The bulk of the levator scapulae and infraspinatus muscles was preserved, but the teres major and latissimus dorsi muscles showed slight enlargement. These

Deltoid Muscle magnetic resonance imaging findings were consistent with the clinical findings. Teres Major Muscle

Latissimus Dorsi Muscle COMMENT

In MM-type dysferlinopathy, personal observations have D Deltoid Muscle revealed thinning of the whole trapezius muscle so that the wasting or enlargement of the underlying muscles is prominent. The upper and lower borders of the trapezius muscle, Depression Due to Fibrosis Near the however, show sparing or enlargement of muscle fibers with Fascia Between the Muscle Bundles possible fibrosis and appear like a cord running from the of the Deltoid Muscle occipital protuberance to the lateral part of the clavicle/ acromion process and lower thoracic spine to the base of the spinous process of the scapula. The upper border of the latissimus dorsi muscle also shows prominence that runs as a cord from the midthoracic spinous process to the in- Figure 2. A patient with Miyoshi myopathy different from the one shown in ferior angle of the scapula and as a bulge in the inferome- Figure 1 demonstrating calf heads on a trophy sign. Oblique sagittal sections of T1-weighted magnetic resonance imaging passing through the planes dial part of the posterior axillary fold just below the axilla; depicted in the clinical photograph are also shown. Note the similarity a part of the teres major muscle also contributes to the lat- between the clinical and magnetic resonance imaging features. ter. The supraspinatus muscle is wasted. The infraspina-

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©2006 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 tus is slightly enlarged and bulges out in its superomedial der is followed laterally by sudden tapering of the upper portion, whereas the inferolateral portion shows wasting. extremity near the middle of the upper arm because of wast- Medial to the wasted supraspinatus muscle, a small bulge ing of all the distal muscles, which looks like the shank of is seen due to preserved or slightly enlarged levator scapu- an animal.17 lae and rhomboideus minor muscles near their insertion The calf heads on a trophy sign was not visible in any to the superomedial border of the scapula. However, a de- patient with muscle disease other than MM and thus ap- pression appears medial to the medial border of the scapula pears to be highly specific. However, its sensitivity needs because of the wasted rhomboideus major muscle. The pos- to be evaluated in a larger number of patients. As the fi- terior axillary fold shows hollowing in its uppermost part nal diagnosis nowadays is made with immunohistochemi- because of wasting of all muscles contributing to it. Supe- cal staining of muscle biopsy specimens and genetic stud- rior to the posterior axillary fold, the deltoid muscle shows ies, the calf heads on a trophy sign may be useful in enlargement of its muscle bundles with deep serrations in directing patients to appropriate tests, thus minimizing between, perhaps because of underlying linear fibrosis along the time and cost of diagnosis. the interfascicular fascia. These findings appear to be the basis for the particular regional topography behind the Accepted for Publication: February 16, 2006. shoulders that is visible when patients with dysferlinopa- Correspondence: Sunil Pradhan, MD, DM, Department thy adopt a particular posture. of Neurology, Sanjay Gandhi Postgraduate Institute of The calf heads on a trophy sign attains special impor- Medical Sciences, Lucknow 226 014, India (drspradhan tance because after adopting a similar posture, patients with @rediffmail.com). Duchenne-Becker muscular dystrophy, facioscapulohumeral dystrophy, and myotonic dystrophy type 1 show specific appearances typical of these disorders.14-17 In pa- REFERENCES tients with Duchenne-Becker muscular dystrophy, adop- 1. Miyoshi K, Saijo K, Kuryu Y, et al. Four cases of distal myopathy in two families. tion of this posture (abduction and external rotation of the Jpn J Hum Genet. 1967;12:113. shoulders) shows enlargement of the deltoid and infraspi- 2. 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