Muscle Atrophy In Pediatric Patients

Introduction

Muscle atrophy, also known as muscle wasting, is a condition characterised by the progressive loss of muscle mass and strength. This phenomenon is particularly significant in pediatric patients, where muscle atrophy can have long-term consequences on their health and development. Understanding muscle atrophy in pediatric patients is crucial because it can impact their ability to recover from illnesses, grow properly, and maintain overall health. In this context, it is essential to identify and manage muscle atrophy early on to prevent negative outcomes and ensure optimal health outcomes for children.¹

Causes of muscle atrophy in pediatric patients

Muscle atrophy in pediatric patients can be attributed to several factors associated with critical illness. Children, like adults, are exposed to various risk factors that can lead to muscle wasting. These include sepsis, hyperglycemia, malnutrition, and prolonged corticosteroid use:

• Sepsis: Sepsis, a severe inflammatory response to infection, can upregulate muscle protein breakdown and impair muscle protein synthesis, leading to accelerated muscle loss
• Hyperglycemia: High blood sugar levels during critical illness can contribute to muscle wasting by promoting protein breakdown and inhibiting protein synthesis
• Malnutrition: Inadequate nutritional intake, common in critically ill children, can deprive the muscles of the necessary building blocks for maintenance and growth, exacerbating muscle atrophy
• Corticosteroid use: Prolonged, high-dose corticosteroid treatment, often used in critical care, can induce muscle wasting by inhibiting protein synthesis and stimulating protein breakdown

Additionally, children may be more susceptible to muscle wasting than adults due to differences in muscle protein turnover. Children are more dependent on growth factors for muscle maintenance and growth, suggesting they may be more vulnerable to muscle loss in the presence of critical illness-related starvation and immobility, especially during periods of rapid growth. However, children also have proportionally fewer type 2 muscle fibres, which are preferentially targeted in ICU-related muscle wasting, potentially resulting in less severe muscle loss. Further research is needed to fully understand the impact of critical illness on muscle protein turnover in pediatric patients.³

Diagnosis of muscle atrophy in pediatric patients

Diagnosing muscle atrophy in pediatric patients typically involves a combination of physical examination, medical history, and diagnostic tests. The following methods are commonly used:

• Genetic tests: These tests evaluate for conditions that tend to run in families. Genetic testing can identify deletions or mutations in the SMN1 gene, which is responsible for spinal muscular atrophy (SMA), a common cause of muscle atrophy in children^2,4,5
• Blood tests: Blood tests can measure levels of creatine kinase (CK), an enzyme that leaks out of deteriorating muscles. While not specific to muscle atrophy, elevated CK levels can indicate muscle damage. Blood tests may also be used to screen for underlying conditions contributing to muscle wasting^2,4
• Electromyography (EMG) and nerve conduction study: These tests measure the electrical activity of nerves and muscles. An EMG can detect abnormal electrical muscle activity due to neuromuscular conditions, while nerve conduction studies assess the speed at which electrical signals travel along nerves^2,4,5
• Muscle biopsy: A small sample of muscle tissue is removed and examined under a microscope to confirm a diagnosis or identify the underlying cause of muscle atrophy. This invasive test is typically reserved for cases where other diagnostic methods are inconclusive^2,4,5

Symptoms and types of muscle atrophy in pediatric patients

Pediatric patients with muscle atrophy exhibit different types and symptoms depending on the age of onset and severity. 

The different types of muscle atrophy in pediatric patients are primarily characterised by the age of onset and severity of symptoms:

• Type I (Werdnig-Hoffman or infantile-onset SMA): This is the most severe form, with symptoms appearing within the first 6 months of life. Infants with Type I SMA have extremely weak and floppy limbs, difficulty feeding and swallowing, and impaired respiratory function. They are unable to sit or stand independently and typically do not live past 2 years of age without advanced medical intervention
• Type II: Symptoms of Type II SMA appear between 7-18 months of age. Children with this form can sit independently but are unable to stand or walk without assistance. They may develop tremors in the fingers and hands, as well as scoliosis and respiratory issues that increase the risk of chest infections
• Type III (Kugelberg-Welander or juvenile SMA): This is the mildest form, with symptoms appearing as late as adolescence. Individuals with Type III SMA can walk independently but may have difficulty running, climbing stairs, or rising from a seated position. They are also at risk of joint contractures and scoliosis
• Type IV: The adult-onset form, Type IV SMA typically begins in early adulthood. Symptoms include progressive weakness in the hands and feet, as well as difficulty walking. However, this form does not typically impact breathing or swallowing

Across all types, muscle weakness and atrophy are the hallmark symptoms, leading to impaired motor function, mobility, and respiratory complications. Early diagnosis and management are crucial to optimize outcomes for children with muscle atrophy.^6,7,8

Long-term effects and outcomes

The long-term effects of muscle atrophy in pediatric patients can be significant and far-reaching. Muscle wasting due to critical illness can result in persistent impairment in physical function and strength, even after the acute illness has resolved. This loss of muscle mass and strength can negatively impact a child's ability to perform daily activities and participate in physical play, potentially hindering their overall development.

Additionally, prolonged muscle loss can reduce bone mineral content and limit growth potential in children, as the reduced mechanical load on the bones leads to decreased bone density. This is particularly concerning in pediatric patients, where muscle and bone development are closely linked.

Studies have shown that physical limitations and functional impairments are common in survivors of critical illness, and these deficits are often associated with the degree of muscle wasting experienced during the acute phase. Understanding the long-term consequences of muscle atrophy in children is crucial for developing effective interventions to prevent and manage this condition, in order to optimise health outcomes and quality of life for pediatric patients.¹

Treatment and management

The key to effectively managing muscle atrophy in pediatric patients is early detection and intervention. 

• Early diagnosis allows for the timely initiation of appropriate therapies, which can significantly improve outcomes for children with muscle atrophy
• The NHS has approved several treatments for spinal muscular atrophy (SMA), a common cause of muscle atrophy in children:
  • Spinraza (Nusinersen): A medication administered via spinal injection that helps increase the production of the SMN protein, which is deficient in SMA
  • Zolgensma: A one-time gene therapy that replaces the defective SMN1 gene, approved for children under 2 years old
  • Evrysdi: An oral medication that helps increase SMN protein production
• Early intervention with these treatments has been shown to improve motor function, developmental milestones, and overall quality of life for children with SMA. The earlier the treatment is started, the better the outcomes, as it can help prevent or slow the progression of muscle wasting

In addition to these targeted therapies, a multidisciplinary approach to management is essential. This includes respiratory support, nutritional interventions, physical and occupational therapy, and assistive devices to maintain function and prevent complications. With a comprehensive care plan tailored to the individual child's needs, many children with muscle atrophy can achieve significant improvements in their condition and quality of life.^4,5,6