Magnetic Resonance Imaging Studies in Duchenne Muscular Dystrophy: Linking Findings to the Physical Therapy Clinic

Senesac C, Barnard AM, Lott DJ, et al. Magnetic Resonance Imaging studies in Duchenne Muscular Dystrophy: Linking findings to the Physical Therapy Clinic. Physical Therapy. 2020;100(11):2035-2048. doi:10.1093/ptj/pzaa140

Link to Original Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596892/

Key Points

1. Duchenne muscular dystrophy (DMD) is a progressive muscle degenerative disorder causing muscle weakness, cardiac impairment, and respiratory insufficiency, primarily caused by mutations in the X chromosome dystrophin gene, leading to contraction-induced damage and muscle cell death.

2. Magnetic resonance imaging (MRI) studies have provided insights into muscle pathology and disease progression in DMD, identifying fatty infiltration and inflammation in muscles as markers of disease severity, with fatty infiltration linked to worsening functional abilities.

3. MRI can be used qualitatively to visualize fatty replacement and inflammation in muscles and quantitatively to measure muscle size, fatty infiltration, and edema, providing objective measures of muscle health and disease progression.

4. MRI findings of muscle pathology in DMD have implications for physical therapy management, guiding the development of evidence-based treatment and care decisions.

5. DMD affects axial, upper and lower extremity muscles progressively, leading to muscle degeneration, weakness, and compensatory movement patterns, impacting posture, ambulatory abilities, and upper extremity function.

6. Physical therapy research in DMD, including the use of quantitative imaging to assess exercise safety and efficacy, as well as management and prevention of contractures, is necessary to optimize therapy recommendations and improve the care of individuals with DMD.

Introduction

Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disorder caused by mutations in the dystrophin gene on the X chromosome. The absence of dystrophin makes muscle cells susceptible to damage and inflammation, leading to muscle cell death and replacement by fibrous and fatty tissue. The primary clinical manifestations of DMD include progressive muscle weakness, signs of proximal muscle weakness such as Gower’s sign, and cardiopulmonary complications that are major causes of death in early adulthood. The progressive muscle weakness starts in the proximal muscles and extends distally, resulting in the loss of independence during the early teenage years. Cardiopulmonary complications occur due to the deterioration of cardiac and respiratory muscles, leading to significant mortality rates. Therapeutic interventions include glucocorticosteroids, which are used to slow the progression of muscle weakness, and cardiac medication to manage symptoms of cardiomyopathy. In the US and Europe, mutation-specific dystrophin restoration therapies are approved.

Physical therapy plays a crucial role in managing musculoskeletal health, even though there is a lack of evidence-based recommendations. Physical therapists address limitations in range of motion, seating and positioning, and prescribe exercises to help maintain a high quality of life. However, the lack of sufficient evidence-based recommendations means that the guidance provided tends to rely on expert opinions rather than data-driven findings.

Magnetic resonance imaging (MRI) techniques have become increasingly utilized to understand and quantify muscle disease patterns in DMD. Qualitative MRI, such as T1-weighted and T2-weighted images, is used to visualize fatty replacement and inflammation. Quantitative MRI measures muscle size, fatty replacement, and edema, providing insights into muscle pathology and disease progression. Higher levels of fatty infiltration in a muscle are linked to worsening functional abilities in individuals with DMD. The article summarizes muscle pathology and disease progression findings from qualitative and quantitative muscle MRI studies, linking MRI findings to clinical observations and discussing the potential implications for physical therapy management. The authors provide representative MRIs to illustrate typical patterns of muscle pathology in major body regions and hope that these insights will facilitate evidence-based treatment and care decisions for individuals with DMD.

Axial Muscles

MRI of Axial Musculature

The research paper focused on the limited clinical and MRI research on axial muscle involvement in Duchenne muscular dystrophy (DMD), despite axial muscles being among the first affected. The study captured evidence of muscle pathology beginning in the early stages of the disease, with fatty infiltration progressing in muscles such as the pectoral, latissimus dorsi, internal oblique, and lumbar paraspinals throughout the ambulatory stage. As the disease progresses, there is near complete replacement of trunk muscles by fat. Additionally, the diaphragm and accessory respiratory muscles play a critical role in ventilation and respiratory health, with fatty infiltration of the diaphragm and other muscles affecting forced vital capacity and maximal expiratory pressures. MRI images revealed decreased diaphragm descent during inspiration in older individuals, along with diminished chest expansion and smaller lung dimensions. Moreover, the muscles responsible for facilitating expiration were also impacted, displaying fatty infiltration, with the internal oblique muscle being the most severely affected. The participants exhibited a forced vital capacity of 93%, but the degeneration of expiratory muscles led to a maximal expiratory pressure of only 51%. The study highlighted the importance of axial muscle involvement in DMD, as respiratory impairment is a later manifestation but crucial for patients' overall health. The findings underscore the need for further research and consideration of the role of axial muscles in DMD, as well as their potential impact on respiratory function and overall disease progression.

Linking MRI Data to Axial Muscle Function

The section "Linking MRI Data to Axial Muscle Function" from the research paper discusses the impact of Duchenne muscular dystrophy (DMD) on various muscle groups and their functional implications, as observed through MRI imaging. It emphasizes the significance of axial muscles in maintaining posture and balance, as well as the compensatory strategies used by individuals with DMD to stabilize their trunk and perform reaching activities. A person with DMD is unable to rely on their arms to stabilize their trunk or prevent falling due to weak trunk muscles. Considering the impact on balance and posture, it is important for physical therapists to focus on reducing the risk of falling, particularly for patients with steroid-induced bone fragility. The study reveals reduced trunk muscle performance and the extensive degeneration of trunk muscles captured in MRI images, emphasizing the need for adequate trunk support and pressure relief measures. Patients with DMD utilize almost all of their arm and muscle strength for reaching activities. As patients with DMD eventually rely solely on wheelchairs, it is essential to provide them with proper trunk support and pressure relief cushions. This is necessary due to the weakening of trunk muscles, which restrict their ability to lean or reposition their bodies. Furthermore, the paper examines how DMD affects respiratory muscles and chest wall mobility. It also proposes the potential advantages of respiratory muscle training, despite the current evidence being low and concerns over muscle damage.

Lower Extremity

MRI of Lower Extremity Musculature

The MRI studies in Duchenne Muscular Dystrophy (DMD) have primarily focused on understanding the lower extremity muscles and its impact on gait and ambulatory abilities. Due to the proximal-to-distal progression of DMD, the gluteal muscles are the first lower extremity muscles to exhibit signs of fatty infiltration. Statistics indicate that 90% of 9 to 10-year-olds have over 60% fatty infiltration in their gluteal muscles. However, the iliopsoas muscles display lower levels of fatty infiltration despite showing higher signs of inflammation compared to the gluteal muscles.In addition to the gluteal muscles, the adductor magnus, biceps femoris, and quadriceps, specifically rectus femoris, display signs of fatty infiltration in the muscles of the lower extremity, particularly in the proximal region. It should be noted that these signs of fatty infiltration are not evenly evident in the upper leg muscles. The sartorius, gracilis, and semitendinosus exhibit a lesser degree of fatty infiltration.

The pathology observed in the lower leg muscles is less severe compared to the upper leg as a result of the disease pattern progressing from proximal to distal. The fibularis longus/brevis, soleus, and gastrocnemius demonstrate the most rapid progression. The tibialis anterior demonstrates an intermediate rate of progression, while the tibialis posterior remains unaffected. Calf hypertrophy is a classic indication of DMD, and MRI studies validate an increased volume of the muscle.

Linking MRI Data to Ambulatory Abilities

The section “Linking MRI Data to Ambulatory Abilities” outlines the progression of fatty infiltration in lower extremity muscles, particularly the gluteal and thigh muscles, as well as the observed gait deviations and compensations. The researchers observe that the first changes in the gait are an increased lumbar lordosis, which compensates for weak gluteal and hip extensor muscles. Additionally, weakness in the gluteus medius and minimus muscles results in a waddling gait and a positive Trendelenburg sign. Gait impairment is also attributed to knee extensor weakness and altered ankle movements. An individual with DMD attempts to decrease knee flexion moment during the loading response phase of the gait by keeping their feet flat or leading with their toes. Moreover, reduced eccentric control of the quadriceps muscles leads to reliance on handrails when going up and down stairs. Performing functional activities like squats and step down movements becomes progressively more challenging. At the ankle joint, a decrease in ankle dorsiflexion is observed during the initial contact. Additionally, ankle inversion is observed during the swing and stance phase in order to compensate for the limited range of motion in ankle dorsiflexion and caused by unaffected tibialis posterior muscle that pull ankles inward.

Quantitative muscle MRI measures can predict future functional changes and guide intervention selection. The loss of ambulation is related to the over 40% replacement of quadriceps muscle with fatty tissue, with various compensatory strategies allowing individuals to continue ambulating despite >70% quadriceps muscle degeneration. Muscle weakness and degeneration lead to compensatory movements such as Gower's maneuver and step-to patterns while ascending or descending stairs. MRI studies also show a correlation between muscle pathology and functional abilities, such as the time to rise from the floor. Despite the muscle degeneration associated with DMD, individuals with this condition show impressive compensatory strategies to preserve their functional mobility skills. It is often counterproductive to try to correct these compensatory strategies. Therefore, caution is advised when implementing management strategies, including the use of ankle-foot orthoses (AFOs), as they may hinder compensatory strategies and exacerbate functional difficulties. Additionally, caution is advised in prescribing strengthening exercises, as eccentric contractions can cause muscle damage in individuals with DMD. The findings highlight the complexity of muscle degeneration in DMD and emphasize the need for careful consideration in managing gait and ambulatory abilities in individuals with DMD.

Linking MRI Data to Lower Extremity Contracture Development

The section "Linking MRI Data to Lower Extremity Contracture Development" in the research paper discusses the focus of physical therapy in preventing and managing lower extremity contractures in individuals with Duchenne muscular dystrophy (DMD). It highlights that plantar-flexion contractures typically emerge during the ambulatory stage, while the loss of hip and knee extension range of motion (ROM) and the progression of ankle contractures to an equinovarus position often occur after the loss of ambulation. The development of contractures in DMD is described as widespread and likely multifactorial, involving factors such as loss of contractile tissue, replacement by fibrofatty tissue, static positioning, and agonist/antagonist imbalance. The paper suggests that contracture development in DMD is influenced by various factors and is not limited to a single cause. This section emphasizes the importance of understanding the complex interplay between these factors in order to effectively prevent and manage lower extremity contractures in individuals with DMD. The role of MRI data is mentioned as a potential tool for gaining insights into the pathophysiology and progression of lower extremity contractures, which could ultimately inform better strategies for their prevention and treatment.

The MRI studies in Duchenne Muscular Dystrophy (DMD) highlight the development of lower extremity contractures and the associated compensatory movement patterns. The sparing of the tibialis anterior compared to the gastrocnemius and soleus muscles suggests that plantar-flexion contracture development in DMD may be multifactorial, driven by fibrofatty changes in the calf muscles, preserved tibialis posterior, and compensatory toe walking. Nonambulatory individuals demonstrate complete fatty replacement of certain muscles, degeneration of calf muscles, and selective sparing of specific muscles, contributing to specific deformities typical of the nonambulatory stage. Additionally, MRI shows the absence of quadriceps and hamstring contractile tissue in nonambulatory individuals, which may contribute to knee flexion contractures. The efficacy of stretching and bracing in the presence of significant loss of muscle contractile tissue and replacement by fibrofatty tissue is not well understood. These findings provide insight into the pathophysiology of contracture development in DMD and may guide future research on the effectiveness of interventions such as stretching and bracing.

Upper Extremity

MRI of Upper Extremity Musculature

The research paper on MRI of Upper Extremity Musculature in individuals with Duchenne muscular dystrophy (DMD) highlights the increasing interest in understanding upper extremity muscle involvement in DMD, particularly as individuals are living longer after losing ambulation. The paper reveals surprising findings from initial imaging studies, demonstrating that shoulder girdle muscle involvement occurs before loss of ambulation, and muscle involvement may be present even before decreases in commonly used assessment scales. Unaffected controls show minimal fatty infiltration of upper extremity muscles, while in DMD, the rotator cuff, deltoid, serratus anterior, and latissimus dorsi muscles are the first to be affected, with signs of fatty infiltration observed in individuals with good upper extremity function scores. The paper also discusses the progression of fatty infiltration and muscle degeneration in both late ambulatory and nonambulatory individuals in the shoulder girdle and forearm muscles. It is noted that forearm muscle progression is slower during the ambulatory phase but increases significantly once individuals become nonambulatory. The findings demonstrate the importance of MRI in understanding the progression of muscle involvement in DMD, particularly in the upper extremities, and highlight the potential for early detection and monitoring of the disease.

Linking MRI Data to Upper Extremity Function

The research paper discusses the limitations of current assessments in detecting early arm muscle pathology and functional limitations in individuals with Duchenne muscular dystrophy (DMD). The paper introduces innovative measures, such as the Reachable Workspace measure using Microsoft Kinect platforms and the physical therapist-developed ACTIVE-Seated measure, which aim to quantify arm function and detect functional impairments in individuals with DMD, even in those with low Upper Extremity Function (UEBS) scores. The study found that individuals with DMD with UEBS scores of 1 exhibited reduced reachable space when the wrist was weighted, indicating early trunk muscle weakness. Additionally, the paper highlights the early and progressive degeneration of shoulder muscles in DMD, leading to impaired shoulder stability and mobility. Shoulder pain and stiffness are reported as individuals with DMD age, which may require attention from physical therapists. The paper also discusses the development of arm support systems to maximize functional shoulder and arm movement and reaching ability, and emphasizes the role of physical therapists in trialing and selecting the most suitable arm support systems based on individual impairments and daily tasks. Lastly, the paper advises against the use of walkers for gait assistance in individuals with DMD, as it may increase the risk of falls and fatigue due to early involvement of axial, shoulder, and arm muscles in DMD.

The MRI studies in Duchenne Muscular Dystrophy highlight the importance of maintaining elbow, forearm, and hand range of motion (ROM) to facilitate independence in daily activities such as self-care, feeding, and operating a powerchair. Fibrofatty infiltration of the biceps brachii and consequent loss of contractile tissue, along with frequent positioning of the arms on wheelchair armrests, contribute to elbow flexion contractures. MRI quantification reveals that the triceps brachii is typically slightly less affected than the biceps brachii in boys and teenagers. While forearm muscle progression is slower in the ambulatory phases, limited supination may occur while still walking, possibly due to the faster progression of specific muscles. Loss of these motions, in combination with elbow contractures, can impact functional activities such as reaching, grooming, self-feeding, and object manipulation. The paper emphasizes the need for further physical therapy research to understand upper extremity contracture pathophysiology and develop prevention and management strategies.

Looking Forward

In the "Looking Forward" section of the research paper on Duchenne muscular dystrophy (DMD), the authors highlight the evolving natural history of the disease and the increased lifespan of individuals with DMD due to the use of corticosteroids. They emphasize the limited scientific literature on physical therapy needs for boys and young men with DMD, particularly in relation to muscle imaging using MRI to understand compensatory mechanisms and disease progression. The potential application of MRI for assessing the safety and efficacy of exercise interventions in DMD is discussed, emphasizing the need for pairing quantitative MRI with high-quality exercise studies to enhance clinicians' understanding of safe vs damaging activities. The authors also stress the importance of studying the impact of dystrophin-restoration therapies on exercise safety and the need for research on contracture management and prevention, including the use of MRI as an adjunct tool. They encourage researchers and clinicians to critically explore the role of physical therapy in DMD using contemporary evidence from imaging studies and high-quality clinical studies. The authors underscore the challenge of enhancing understanding of DMD and improving therapy recommendations for families, emphasizing the responsibility of providers to use current literature, including imaging research, to inform best practices and shape future interventions for individuals with DMD at different levels of impairment, activity, and participation.

Opportunities for Future Research

1. Safety and efficacy of exercise intensities and regimens: Future research could investigate the safety and efficacy of different exercise intensities and regimens for individuals with DMD, using quantitative imaging measures such as MRI to assess any increase in skeletal muscle inflammation or edema.

2. Contracture management and prevention: There is a need for randomized clinical trials to investigate the benefits of bracing, casting, stretching, and other interventions for lower extremity contracture management in DMD, as well as to differentiate the nature and mechanisms of contractures in this population.

3. Physical therapy interventions and dystrophin-restoration therapies: Further research is needed to understand how dystrophin-restoration therapies affect exercise safety and to assess the benefits and risks of carefully prescribed inspiratory and expiratory muscle training in DMD.

4. Upper extremity muscle involvement: Additional studies could explore upper extremity muscle involvement in DMD, including the progression of shoulder girdle and upper arm muscle fatty infiltration and its impact on functional abilities, as well as the development of upper extremity contractures.

5. Functional assessments in DMD: Research could focus on the development of innovative measures to quantify early arm function or strength impairments in individuals with DMD, which may provide valuable insights for physical therapists.

6. Exercise safety and efficacy with high-quality clinical studies: There is an opportunity to continue pairing quantitative MRI with high-quality exercise studies in DMD to better understand the safety of specific exercise regimens and activities for individuals with DMD.