MYOPATHIES: Skeletal muscle disorders

Myopathies constitute a heterogeneous group of disorders affecting the structure or function of skeletal muscles—those responsible for voluntary movement by attaching to bones.

The main shared clinical feature is muscle weakness, and myopathies must be distinguished from neuropathies, motor neuron diseases, or neuromuscular junction disorders.

In terms of classification, myopathies are broadly divided into hereditary and acquired types, with further subdivisions as outlined below.

Hereditary Myopathies

Congenital Myopathies

Typically manifesting in the neonatal period, infancy, or childhood, congenital myopathies present with generalized symptoms and delayed motor milestones (e.g., walking), usually without progressive deterioration.

Muscular Dystrophies

These are caused by mutations in genes encoding proteins like dystrophin, essential for maintaining muscle cell membrane integrity. This group includes:

• Duchenne and Becker muscular dystrophies

• Myotonic dystrophies types I and II

• Facioscapulohumeral (FSH) dystrophy

• Oculopharyngeal muscular dystrophy

Mitochondrial Myopathies

Due to mutations in mitochondrial DNA, often involving additional organ systems (CNS, heart, GI tract). Examples include MELAS, MERRF, and Kearns-Sayre syndrome.

Metabolic Myopathies

Includes glycogen storage diseases (e.g., Pompe disease) and lipid metabolism disorders leading to muscle dysfunction.

Channelopathies

Includes:

• Familial periodic paralysis (hypokalemic or hyperkalemic)

• Congenital myotonias (e.g., Steinert’s and Thomsen’s diseases), marked by delayed muscle relaxation following contraction

Acquired Myopathies

Autoimmune or Idiopathic Inflammatory Myopathies

Examples: polymyositis, dermatomyositis, inclusion body myositis

Toxic or Drug-Induced Myopathies

Common culprits: statins, corticosteroids, alcohol, cyclosporine, amiodarone

Infectious Myopathies

• Bacterial: e.g., Lyme disease

• Viral: e.g., HIV, Coxsackie, influenza

• Parasitic: e.g., toxoplasmosis

• Fungal: less common

Endocrine Myopathies

Associated with:

• Diabetes mellitus

• Thyroid dysfunction (hyper/hypothyroidism)

• Hyperparathyroidism

• Adrenal disorders (e.g., Cushing’s syndrome, Addison’s disease)

Electrolyte-Related Myopathies

Due to potassium imbalance, hypercalcemia, hypermagnesemia, or hypophosphatemia

Systemic Disease–Related Myopathies

Secondary to conditions such as amyloidosis, sarcoidosis, or paraneoplastic syndromes

Symptoms

The hallmark symptom is muscle weakness, often proximal and symmetrical, affecting the shoulder and pelvic girdles. Patients frequently report:

• Difficulty rising from a chair

• Trouble climbing stairs

• Inability to lift arms above shoulder level

Myalgia (deep muscle pain), especially in large muscle groups, is another frequent symptom. It must be distinguished from myofascial pain syndrome, a localized pain condition linked to muscle strain, poor posture, or environmental exposure, typically associated with trigger points.

Other reported symptoms include:

• Fasciculations (twitching felt under the skin)

• Cramps

• Generalized fatigue and easy fatigability

• Less commonly: diplopia, ptosis, dysphagia, dysarthria

• Abnormal trunk posture: winged scapula, hyperlordosis, scoliosis

• Dyspnea, dark-colored urine

• Notably, sensory symptoms are absent

Diagnosis

Diagnosis is based on clinical suspicion and includes:

• Comprehensive medical and family history: Include comorbidities, medication use (e.g., statins), symptom progression, weight changes, urine color, and similar symptoms in relatives.

• Neurological examination: Assess distribution and severity of muscle weakness, muscle atrophy or hypertrophy, rashes, arthritis signs, or other systemic findings.

• Laboratory testing:

  • Creatine kinase (CK) levels are crucial; values >10x normal suggest myopathy.

  • Persistent CK elevation, even without symptoms, warrants further investigation.

• Cardiac evaluation: ECG, Holter, echocardiogram or MRI, to detect cardiac involvement.

• Electromyography (EMG): To identify a myopathic pattern—mandatory in suspected cases.

• Nerve conduction studies: To exclude neuropathies and neuromuscular junction disorders.

• Muscle MRI: Reveals fatty degeneration of involved muscles.

• Muscle biopsy: Gold standard for mitochondrial, metabolic, or inflammatory myopathies. EMG/MRI help determine the biopsy site.

• Genetic testing: Essential for diagnosing hereditary myopathies.

  
  

Prognosis

Prognosis varies based on the type of myopathy:

• Hereditary myopathies may involve systemic complications like hypertension, hearing loss, cataracts, seizures, infections, rhabdomyolysis, arrhythmias, or organ failure.

  A classic example is Duchenne muscular dystrophy (DMD):

  • Affects boys

  • Onset ~4 years old

  • Loss of ambulation by ~12 years

  • Life expectancy ~28–30 years

  • Cause of death: cardiorespiratory failure

• Some hereditary myopathies respond to treatment (e.g., corticosteroids in DMD), but most require supportive care:

  • Nutritional support

  • Physiotherapy, occupational therapy, speech therapy

  • Genetic counseling is critical

• Acquired myopathies often improve with:

  • Removal of causative agent (e.g., stopping a drug)

  • Treating underlying conditions (e.g., correcting thyroid/electrolyte imbalance)

  • Immunomodulatory or immunosuppressive therapy, especially in autoimmune forms

Conclusion

Patients presenting with symptoms suggestive of myopathy should be promptly referred to a neurologist experienced in neuromuscular disorders and capable of performing neurophysiological testing. Diagnosis is often complex and requires a multifaceted clinical, laboratory, and imaging approach. A timely and accurate diagnosis is crucial for effective management and improved outcomes.