LEC 1 non-neoplastic skeletal muscle diseases

• • Disruption in the neuromuscular junction causes nerve signals to fail to communicate properly with muscles
  • Autoantibodies target acetylcholine receptors on muscle cells, leading to reduced muscle responsiveness to nerve signals
  • Muscle weakness and fatigue occur, especially during repetitive stimulation
  • Trigger for autoantibody development involves genetic predisposition and environmental factors
  • Clinical manifestations include muscle weakness, fatigue, ptosis, diplopia, difficulty in chewing, swallowing, speaking, and respiratory muscle weakness
• Myasthenia gravis:

  • Caused by autoantibodies that block the function of postsynaptic acetylcholine receptor antibodies, leading to receptor aggregation or degradation and damage to the postsynaptic membrane through complement fixation
  • Can manifest at any age and is more common in females
  • About 60% of cases are associated with thymic hyperplasia, while 20% are associated with thymoma
  • Thymic lesions may disturb tolerance to self-antigens, leading to the generation of autoreactive T and B cells
• • Complications such as aspiration pneumonia and myocarditis
• Dystrophinopathies (Duchenne and Becker muscular dystrophy):

  • Mutations in the dystrophin gene on the X-chromosome cause both conditions
  • Duchenne muscular dystrophy has an incidence of about 1 per 3500 live male births and follows a fatal course
  • Becker muscular dystrophy is a slowly progressive form with the same gene affected as Duchenne muscular dystrophy
  • Absence of dystrophin protein in skeletal muscle is the primary cause of these conditions
  • Muscle biopsy immunostaining in Becker muscular dystrophy shows altered size and decreased amount of dystrophin
• • Disorder of function or decreased amount of dystrophin rather than absence of the protein
  • Duchenne muscular dystrophy clinically evident by age 5, wheelchair-bound by teenage years, with various muscle weaknesses and gait abnormalities
  • Becker muscular dystrophy is a slowly progressive form with similar manifestations to Duchenne muscular dystrophy
• • Can manifest as a paraneoplastic disorder in adults

  Inclusion Body Myositis:

  • Most common inflammatory myopathy in individuals over 60 years with a chronic, progressive course
  • Rim vacuoles contain aggregates of proteins associated with neurodegenerative diseases
  • Shows features of chronic inflammatory myopathies, including myopathic changes, mononuclear cell infiltrates, endomysial fibrosis, and fatty replacement
  • Generally does not respond well to immunosuppressive agents
• Inflammatory myopathies (polymyositis, dermatomyositis, and inclusion body myositis):

  Polymyositis:

  • Autoimmune disorder with increased MHC class I molecules on myofibers and inflammatory infiltrates containing CD8+ cytotoxic T cells
  • Leads to myofiber necrosis and muscle weakness
  • Treatment involves corticosteroids or other immunosuppressive agents

  Dermatomyositis:

  • Believed to have an autoimmune basis with upregulated type I interferon-induced gene products in affected muscles
  • Specific autoantibodies present, such as those against Mi-2, p155, and p140