Sonoelastography of the trunk and lower extremity muscles in a case of Duchenne muscular dystrophy

Abstract

Duchenne muscular dystrophy (DMD) is a rare genetic disorder typically presenting with muscle weakness and reduced tone of trunk and lower extremities. The sonoelastographic properties of DMD are poorly understood. We describe sonoelastographic characteristics of a patient’s trunk and lower extremity musculature. An 8-year-old male presented with a 5-year history of DMD. Sonoelastographic measures of the gluteus maximus and medius, lumbar erector spinae, rectus abdominis, rectus femoris, biceps femoris, tibialis anterior, medial and lateral gastrocnemius muscles were obtained. Sonoelastography demonstrated increased elasticity by elevated kiloPascals (kPa) across all muscles, except the lumbar erector spinae. Patient values were compared to an age-matched healthy control. These abnormal sonoelastographic findings reflected the pathological mechanical properties of DMD. Sonoelastography was valuable for characterizing the mechanical properties of normal and abnormal muscle tissue. There is limited information on the sonoelastography application to DMD. Sonoelastography may serve as a useful measure for diagnosis and monitoring clinical outcomes for DMD.

Introduction

Neuromuscular disorders, such as intermediate muscular dystrophy and Becker’s muscular dystrophy, inclusion-body myositis, and focal neuropathies, change the US echogenicity of muscle tissue similarly to Duchenne muscular dystrophy (DMD) [1]. DMD is a rare X-linked genetic disorder occurring in one in 3600–6000 live births [2–4]. It occurs as a result of deletions or mutations in the dystrophin gene. Dystrophin is a protein that links the extracellular matrix and the actin filaments within the muscle cell allowing muscle contraction [5, 6]. This lack of contraction clinically manifests as proximal muscle weakness. Patients are, thus, compelled to utilize their hands and arms to elevate their trunk relative to their thighs. This is the Gower’s sign. As the disease progresses, continued loss of dystrophin results in uncontrolled extracellular matrix components around the affected muscle cells. Uncontrolled extracellular matrix proceeds to fibrosis and loss of tissue function [6]. Most patients are diagnosed by age 5 due to severe delay in physical milestones. If left untreated, most patients with DMD lose independent ambulation by the age of 13. Non-musculoskeletal manifestations of DMD are characterized by morbidity and mortality. Respiratory and cardiac complications follow, including cardiomyopathy and depressed respiratory function. Death typically occurs in late adolescent to young adulthood [2, 3].

Imaging, such as ultrasound (US) [7–10] and magnetic resonance imaging (MRI) [11–14], has been utilized in the assessment and monitoring of the musculoskeletal system during clinical progression of DMD. US demonstrates an increase in echogenicity due to fatty replacement and fibrosis of muscles [7–10]. MRI similarly shows an increase in muscle signal intensity on T1-weighted sequences corresponding to fatty infiltration and intramuscular edema on fluid-sensitive sequences [11, 12]. Sonoelastography, such as shear wave (SWE), is utilized in the assessment of the mechanical properties of tissues, measured in kiloPascals (kPa) [15, 16]. The utilization of US SWE in Duchenne’s has been minimal. The principle findings reported have been the abnormal muscle architecture of DMD and increases in SWE when compared to normal muscle [17, 18]. This case report adds to the foundation for the growing application of US SWE in the evaluation of DMD.

Case report

An 8-year-old male presented with a history of DMD. He was initially diagnosed at age 3 following an evaluation of his unsteady gait while walking and running. Although there was no family history, genetic testing identified his mother as a carrier. He presented to a chiropractor for palliative care of low back and bilateral leg pain and headaches. The patient did not present with any respiratory or cardiac symptoms. His current medications included prednisone (175 mg once a week), lisinopril (10 mg daily), and eplerenone (25 mg daily) due to increased troponin levels and cardiac fibrosis decreasing his ejection fraction.

His physical examination revealed a mild waddling gait with positive bilateral Trendelenburg test, bilateral pseudohypertrophy of the calf muscles, and normal spinal ranges of motion. His spinal erector muscles were hypertonic bilaterally along with the calves and hamstrings. Passive straight leg raise caused pain in the hamstrings and calves at approximately 30° of hip flexion. Calf pain was also provoked with 80° of ankle dorsiflexion. Prone active hip extension reproduced his chief complaint of low back pain with limited gluteal muscle contraction. He was unable to climb a flight of stairs without assistance.

Sonography was ordered to assess progression of muscle fatty infiltration and fibrosis of the lumbar erector spinae, gluteal maximus and medius, rectus abdominis, rectus femoris, biceps femoris, adductor magnus, and medial and lateral gastrocnemius muscles. A Logiq E9 (GE Healthcare, Wauwatosa, WI) ultrasound system operating at 15 MHz with high-frequency linear array transducer and coupling agent was employed. All muscles were assessed in long axis with a region of interest within the belly of the muscle. An age-matched control subject was utilized for comparison measures. Generalized increase in echogenicity of the muscles was observed, except for the lumbar erector spinae (Fig. 1a, b). The SWE values for the DMD patient and control are in Table 1. A noticeable SWE increase in the tibialis anterior and gluteus maximus muscles was seen in the DMD patient compared to the control subject along with a notable SWE decrease of the lumbar erector spinae muscles (Fig. 1a, b).

Fig. 1.

Sonoelastography of the left and right tibialis anterior muscle (arrows) in a patient with DMD (a, b) versus a normal age-matched control (c, d). There is an increase muscle strain and B-mode echogenicity in the DMD patient

Table 1.

Elastographic values comparing the DMD patient to an age-matched control volunteer

DMD elastography (kPa)			Age-matched control elastography (kPa)
Muscle	Right	Left	Muscle	Right	Left
Medial gastrocnemius	35	54.01	Medial gastrocnemius	47.65	45.11
Lateral gastrocnemius	47.33	46.95	Lateral gastrocnemius	21.12	24.84
Rectus femoris	33.83	44.6	Rectus femoris	40.83	43.08
Biceps femoris	23.51	30.06	Biceps femoris	22.69	28.72
Tibialis anterior	89.66	101.89	Tibialis anterior	71.86	66.18
Gluteus maximus	24.76	29.16	Gluteus maximus	9.87	13.03
Gluteus medius	36.39	20.32	Gluteus medius	16.03	33.85
Lumbar erectors	18.93	17.06	Lumbar erectors	42.26	30.74
Adductor magnus	19	63.48	Adductor magnus	13.76	24.66
Rectus abdominis	34.09	21.67	Rectus abdominis	30.12	25.15

It is noted that the gluteus maximus and tibialis anterior muscles demonstrated elevated values, and the lumbar erector spinae muscles showed decreased values in the DMD patient compared to the age-matched control

The patient’s course of care included spinal mobilization and kinesiotaping of the gluteus maximus and medius and the lateral abdominal raphe. He was seen 2–3 times a week for 2 weeks. Additionally, he was fitted for foot orthotics to assist with the abnormal gait. The patient reported pain reduction in low back and leg pain, mild improvement in gait was observed, and was able to climb a flight of stairs with minimal assistance. The patient was subsequently lost to follow-up.

Discussion

The hallmark of DMD is the genetic loss of dystrophin. Dystrophin is a large protein that helps to stabilize the sarcolemma in muscle fibers. Lack of this important protein results in contraction-induced muscle damage. Once the muscle is damaged, it cycles through necrosis and repairs eventually being replaced by fibrofatty tissue. Excessive fibrofatty tissue deposition leads to loss of muscle mass and function; hence, patients present with proximal muscle weakness and eventual cardiac failure [5, 6, 19]. Prompt diagnosis of DMD can be difficult and is extremely important in the prognosis. The Delphi Consensus Initiative developed a summary of clinical statements to reduce the time between presentation and diagnosis [20]. The largest agreed consensus statement included the recognition of symptoms, such as calf pseudohypertrophy, delayed walking, difficulty climbing/descending stairs, difficulty rising from the floor, elevated serum CK levels, frequent falls, family history of DMD, male gender, Gower’s sign, and muscle weakness. Most of these findings were identified in our patient. Autism spectrum disorder or cognitive/speech delays may also be included, but not always present as in our case, in the disease [20]. Loss of muscle function and age has been linked to a loss of bone mineral density, which may be related to the ambulatory state of the patient [21]. Imaging, such as diagnostic US and MRI, is also helpful in establishing diagnosis and progression of DMD.

Normal muscle tissue on US is hypoechogenic with interspersed sheets of echogenic perimysium giving a “starry night” appearance in short axis and a pennate pattern in long axis (Fig. 1c, d) [1, 22]. Muscle thickness and cross-sectional area can be assessed utilizing US, and has an excellent (0.99) correlation with MRI [1]. Fibrofatty infiltration in DMD demonstrates echogenic muscle changes and atrophy (Fig. 1a, b) [7–10]. Subtle echogenicity changes may be difficult to assess and depends on the operator (low inter-observer agreement) [1]. Maximal operator-induced pressure improves the intraclass coefficient (0.92) in the assessment of muscle echointensity [9]. Quantitative US assessment of muscle echogenicity increased the interobserver agreement (0.53–0.86) [1]. This technique utilizing quantitative back scatter analysis and gray-scale levels demonstrated higher sensitivity in DMD muscle deterioration compared with clinical functional assessments [10].

Elastography is another US tool to assess muscle stiffness [15, 16]. Although muscle biopsy is the standard of histologic diagnosis in DMD, US may be a noninvasive approach to assess muscle changes associated with DMD [17]. Lacourpaille et al. demonstrated increased SWE values in the medial gastrocnemius, tibialis anterior, vastus lateralis, biceps brachii, triceps brachii, and abductor digiti minimi muscles in DMD patients compared to age-matched controls [17]. Our patient has shown similar findings in the gluteus maximus (mean 27 kPa versus 21.9 kPa), although our tibialis anterior measurements were much higher (mean 96.8 kPa versus 23.1 kPa). Furthermore, Pichiecchio et al. found moderately higher SWE values in the rectus femoris, vastus lateralis, adductor magnus, and gluteus maximus (13.92 kPa) muscles of DMD patients compared to age-matched controls [18]. Our patient demonstrated higher elastographic measurements in the gluteus maximus (27 kPa). Pichiecchio et al. compared the SWE values to the amount of fatty infiltration of the muscles on MRI. All subjects demonstrated some degree of muscle fatty infiltration and edema on MRI. Although, there was no significant correlation between SWE and the amount of fatty infiltration of the muscle [18]. Additional research is needed to correlate US findings and the components of the clinical presentation.

Magnetic resonance imaging (MRI) has been the modality of choice for evaluating disease progression and treatment response in DMD. Polavarapu et al. established a typical muscle pattern of fibrofatty infiltration on MRI [11]. Using the Mercuri scoring classification of severity, they found moderate to severe fibrofatty infiltration of the gluteus maximus and quadriceps muscles with relative sparing of the gracilis, sartorius, and semimembranosus muscles. In the lower leg, the superficial posterolateral muscles were involved more frequently than the deep posterior and anterior leg muscles, including the anterior tibialis muscle. Patchy muscle edema was also noted in DMD-affected muscles on MRI and was not strongly correlated with clinical manual muscle testing scores [11]. Li et al. found similar muscle infiltration patterns of the lower extremity, although as the disease progressed with age, the unaffected muscles quickly became involved after the age of 7 [12]. Diffusion tensor imaging (DTI) is an emerging technique for assessing changes in DMD skeletal muscle [13, 14]. Ponrartana et al. found that fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were strongly correlated with age, muscle strength with FA positively correlated with age, and ADC positively correlated with muscle strength [14].

While there is no cure for DMD, treatment advances are quickly emerging [23, 24]. Gene editing and therapy, including dystrophin gene replacement, genetic modification to dystrophin expression, and modulation of dystrophin homologue, in animal models have shown promising results in muscle function restoration [23, 24]. Stem cell research has shown benefits for muscle regeneration, although no pharmacologic treatment protocols have been established [25]. Palliative care, including spinal manipulation and rehabilitation, has been proposed as a non-pharmacologic form of pain management, although more research is needed [4]. Integrative management within multiple specialties is strongly encouraged in the management of DMD [4].

In conclusion, DMD is a complex multi-system genetic disorder affecting muscles throughout the body, starting in the proximal limbs. US may be a more cost-effective way of assessing muscle fibrofatty infiltration and contractile properties utilizing elastography in patients with DMD. Elastographic measurements are generally increased compared to age-matched controls, especially the gluteus maximus and tibialis anterior muscles. More research is needed in the US assessment of dynamic muscle evaluation and its correlation with clinical testing. This may lead to the capacity for earlier DMD diagnosis. MRI may be utilized as a companion form of imaging for US. Although there is no cure for DMD, US imaging may be a more cost-effective option to assess disease progression or response to treatment.

Funding

No finding was received.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in the study.