Myopathy

Diagnosis

Diagnosing myopathy requires a mix of clinical evaluation and several types of testing, since no single test works for every form. The most common lab marker for muscle injury is serum creatine kinase, often checked alongside aldolase, lactate dehydrogenase, and aminotransferases, but a high CK level alone isn’t specific to myopathy. If an idiopathic inflammatory myopathy is suspected, doctors should test for myositis-specific autoantibodies before starting immunosuppression.

Electromyography and nerve conduction studies can tell apart myopathic and neurogenic weakness, and when a myopathic EMG appears with proximal weakness and high CK, a muscle biopsy is more likely to be useful. MRI of muscle can examine deep areas, find subtle involvement, and help pick a biopsy spot. Muscle biopsy with histological, histochemical, and immunohistochemical analysis is still key for confirming inflammatory and structural myopathies.

For inherited forms, genetic testing using next-generation sequencing panels can confirm the diagnosis and often make a biopsy unnecessary.

Pathophysiology

Myopathies share impaired skeletal muscle fiber function but arise through diverse mechanisms. Inherited myopathies involve pathogenic variants disrupting structural proteins, ion channels, or enzymes of muscle energy metabolism.

Metabolic myopathies impair ATP production, causing dynamic symptoms precipitated by exertion. Idiopathic inflammatory myopathies involve immune-mediated endomysial inflammation, with subtypes including dermatomyositis, polymyositis, immune-mediated necrotising myopathy, anti-synthetase/overlap myositis, and inclusion-body myositis. Acquired myopathies from systemic disease act through endocrine dysregulation, drug and toxin exposure, critical illness, and paraneoplastic mechanisms.

Systemic diseases

Myopathies in systemic disease result from endocrine, inflammatory, paraneoplastic, infectious, drug- and toxin-induced, critical illness, metabolic, collagen-related, and other systemic disorders. Patients with systemic myopathies often present acutely or subacutely, whereas familial myopathies or dystrophies generally present chronically, except metabolic myopathies which can be precipitated acutely. Metabolic myopathies affecting ATP production typically present with dynamic exercise-induced symptoms.

Most inflammatory myopathies can have a chance association with malignant lesions, with incidence specifically increased only in dermatomyositis. Muscular dystrophies are a subgroup characterized by muscle degeneration and regeneration, typically progressive, leading to wheelchair use and death from respiratory weakness. Congenital myopathies show characteristic microscopic changes without progressive dystrophic process or inflammation, including nemaline myopathy, multi/minicore myopathy, and centronuclear myopathy.

Mitochondrial myopathies result from defects in mitochondria. Inflammatory myopathies involve immune system attacks on muscle. Metabolic myopathies result from defects in biochemical metabolism primarily affecting muscle, including glycogen storage diseases.

Did You Know?

• Muscular disease can be classified as neuromuscular or musculoskeletal in nature.
• Different myopathies may be inherited, infectious, non-communicable, or idiopathic.