Muscle Biopsy in Pediatric Medicine

Pediatric Procedures Introduction Clinical Indications Procedure Types & Technique Specimen Processing Interpretation & Diagnosis

Key Points

• Gold standard for diagnosing many neuromuscular disorders
• Two main techniques: Open biopsy and Needle biopsy
• Requires specialized processing and interpretation
• Common sites: quadriceps, biceps, deltoid
• Essential tool for diagnosing muscular dystrophies and myopathies

Overview

Muscle biopsy is a crucial diagnostic procedure in pediatric neuromuscular medicine, providing vital information about muscle structure, protein expression, and metabolic processes. The procedure involves removing a small piece of muscle tissue for detailed histological, histochemical, and molecular analysis.

Clinical Indications

Primary Indications

• Muscular Dystrophies
  • Duchenne and Becker muscular dystrophy
  • Limb-girdle muscular dystrophies
  • Congenital muscular dystrophies
• Congenital Myopathies
  • Nemaline myopathy
  • Central core disease
  • Multicore myopathy
• Metabolic Myopathies
  • Mitochondrial disorders
  • Glycogen storage diseases
  • Lipid storage myopathies
• Inflammatory Myopathies
  • Juvenile dermatomyositis
  • Polymyositis
  • Other inflammatory conditions

Pre-biopsy Evaluation

• Comprehensive clinical history
• Physical examination findings
• Creatine kinase levels
• EMG/NCS results
• Genetic testing results (if available)
• MRI findings (when indicated)

Procedure Types & Technique

Open Biopsy Technique

1. Site Selection Considerations
   • Moderately affected muscle (avoid severely affected or normal muscle)
   • Easily accessible location
   • Avoid previously injected sites
2. Procedure Steps
   • Local or general anesthesia based on age
   • 3-4 cm incision
   • Longitudinal orientation along muscle fibers
   • Collection of 1-2 cm³ sample
   • Careful handling to prevent crush artifacts

Needle Biopsy Technique

1. Advantages
   • Less invasive
   • Smaller scar
   • Quicker procedure
2. Limitations
   • Smaller sample size
   • May miss focal pathology
   • Limited orientation of specimen

Specimen Processing

Immediate Handling

• Fresh Tissue Processing
  • Snap freezing in isopentane
  • Temperature control at -160°C
  • Proper orientation of fibers
• Multiple Sample Preparation
  • Frozen sections for histochemistry
  • Formalin fixation for routine histology
  • Glutaraldehyde for electron microscopy
  • Fresh tissue for biochemical studies

Essential Staining Techniques

• Routine Stains
  • H&E (basic architecture)
  • Modified Gomori trichrome
  • PAS for glycogen
• Enzyme Histochemistry
  • ATPase for fiber typing
  • NADH-TR for oxidative activity
  • SDH and COX for mitochondrial function
• Immunohistochemistry
  • Dystrophin analysis
  • Sarcoglycan proteins
  • Other membrane proteins

Interpretation & Diagnosis

Key Histological Patterns

• Dystrophic Pattern
  • Fiber size variation
  • Necrosis and regeneration
  • Increased endomysial connective tissue
• Inflammatory Pattern
  • Perivascular inflammation
  • MHC-I upregulation
  • Perifascicular atrophy
• Metabolic Pattern
  • Ragged red fibers
  • Glycogen accumulation
  • Lipid storage
• Congenital Myopathy Pattern
  • Specific structural abnormalities
  • Fiber type disproportion
  • Central cores or nemaline rods

Further Reading

• Current Approach to Muscle Biopsy - Comprehensive Review
• Washington University Muscle Biopsy Resource
• Muscle Gene Table
• World Muscle Society Guidelines