Myopathies

Myopathies are a heterogeneous group of conditions affecting muscle usually without involvement of the nervous system and independent of any disorder of the neuromuscular junction. They have a diverse aetiology.

The muscular dystrophies are the most common of such disorders and Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy. However the broad range of myopathies is outlined in the boxes below which include some of the rare primary disorders of muscle as well as acquired myopathies.

The subsequent sections put these conditions in context and highlight some contrasting diagnostic and clinical features. Most of the congenital myopathies are chronic and slowly progressive. However, metabolic, inflammatory, toxic and endocrine myopathies present subacutely or even acutely and this requires awareness amongst front line physicians to recognise and diagnose myopathy.

The primary myopathies^1,2,3,4

The acquired myopathies

These are all relatively uncommon diseases:

• DMD is easily the most common childhood-onset muscular dystrophy and affects 1 in 3300 boys. The prevalence of DMD is 63 cases per million.
• The prevalence of the Becker phenotype is 24 cases per million.
• Congenital muscular dystrophy is approximately 50% as common as DMD.

Clinical features of myopathy

• The hallmark symptom of myopathy (and neuromuscular disease) is weakness
• Weakness predominantly affecting proximal muscle groups (shoulder and limb girdles) is typical
• Weakness manifests itself in different ways at different ages:
  • Decreased foetal movements movements in utero
  • Floppy infant neonatally
  • Motor delay in the toddler years
  • Reduced muscle strength and power in older children and adults
• Myalgia may occur in inflammatory myopathies
• Muscle-stretch reflexes are preserved
• Somatosensory reflexes are preserved
• Variation of strength with exercise (either increasing or decreasing) can occur:
  • Fluctuating muscle power suggests metabolic myopathy (for example McArdle disease)
  • Fatigability (or progressive weakness with exertion, relieved by rest) is a feature of myasthenia gravis where the defect is in neuromuscular transmission

History

• Common symptoms:
  • Symmetrical proximal muscle weakness
  • Malaise
  • Fatigue
  • Absence of sensory symptoms (paraesthesia)
  • Atrophy of muscles (and reduced reflexes) occurs late with myopathies (early with neuropathy)
  • Waddling gait of DMD at age 3-6 years is typical
• How acute are the symptoms?
  • Weakness over hours suggests toxic cause or episodic paralysis
  • Weakness developing over days - consider dermatomyositis or rhabdomyolysis
  • Weakness over weeks suggests polymyositis, steroid myopathy, endocrine myopathy
• Pain and tenderness without weakness - consider other causes
  
  
• Which muscle groups are affected?
  • Proximal muscle groups - difficulty rising from chair, climbing stairs, shaving, hair combing
  • Distal muscles - difficulty walking (flapping gait), grasping, handwriting
• Metabolic myopathies present with:
  • Difficulty with exercise
  • Cramps and myalgia with exercise (early with glycogen storage disorders and after prolonged exercise with lipid storage disorders)
  • Myoglobinuria
  • Progressive muscle weakness in some metabolic myopathies
• Past medical history:
  • Autoimmune disease:
    • Systemic lupus erythematosus
    • Rheumatoid arthritis
    • Polyarteritis nodosa
  • Endocrine disease
  • Renal disease
  • Alcoholism
• Family history:
  • Muscular dystrophy
  • Other relevant conditions or myopathies
• Medication:
  • Steroids
  • Lipid lowering drugs
  • Alcohol
  • Colchicine
  • Heroin
  • Azidothymidine
• Occupational history:
  • Pottery industry - glazing salts can cause hypokalaemic paralysis.

Examination

• Symmetrical proximal muscle weakness
• Muscle tenderness very rare with myopathy
• Fever with inflammatory causes
• There is usually no wasting but there may be hypertrophy of muscle (atrophy is a late sign)
• Reflexes and sensation usually normal
• Hypotonia is common in some myopathies (for example congenital myopathies)
• There may be helpful additional signs such as the skin changes of dermatomyositis
• Urine should be examined - myoglobinuria in acute alcoholic myopathy can cause renal tubular necrosis

This list includes other conditions causing weakness:

• Guillain-Barré syndrome
• Eaton-Lambert myasthenic syndrome
• Myasthenia gravis
• Cerebral palsy
• Spinal muscular atrophy
• Congenital hypomyelinating neuropathies

• It may be difficult to distinguish myopathy from peripheral neuropathy. The distinguishing clinical features of peripheral neuropathy are:
  • Weakness affects distal muscles- although there are exceptions:
    • Myopathy where distal muscle groups are affected (myotonic dystrophy, myopathy of Welander)
    • Peripheral neuropathies which affect proximal muscles (diabetic amyotrophy, motor neurone disease)
  • Reduced muscle - stretch reflexes
  • Fasciculations
  • Somatosensory abnormalities
• Some complex cases may have both neurogenic and myopathic disorders which can lead to diagnostic confusion:
  • Diabetes mellitus can cause both neuropathy and inflammatory myopathy
  • Cancer can cause dermatomyositis and chemotherapy peripheral neuropathy in the same patient
  • Radiculopathy (from degenerative disc disease) can occur in patients with myopathy

Blood and urine tests

These together with electrocardiogram (ECG) examination are most useful in acute situations.

• Creatine kinase (with isoenzymes)
• Electrolytes including calcium and magnesium
• Serum myoglobin
• Urea and serum creatinine
• Urinalysis and urine microscopy - myoglobinuria inferred by positive urinalysis with few red cells at microscopy
• Full blood count
• Erythrocyte Sedimentation Rate test (ESR)
• Thyroid function tests
• Antinuclear antibodies

ECG

May show:

• Changes of hypokalaemia - increased P-R interval, U waves, wide QRS and nonspecific ST-T changes
• Sinus arrhythmias, deep Q waves and elevated R waves precordially (for example in DMD)

Muscle biopsy

Muscle biopsy is important in diagnosis but findings under the microscope are rarely pathognomonic. Interpretation requires close consideration of the clinical history in conjunction with the microscopic features to make a diagnosis.

Electromyography

• Excludes primarily neurogenic processes (for example spinal muscular atrophy)
• Proximal muscles of lower extremities often exhibit most prominent features
• Often helps to confirm diagnosis but not in itself diagnostic

Magnetic Resonance Imaging (MRI)

• May help exclude neurological disease
• May help in assessing complications (musculoskeletal or involving other organs)

Genetic testing

The genetic basis of the primary myopathies means that genetic testing can be essential to the specific diagnosis.

This depends on the diagnosis as well as the severity and extent of disease.

Emergency management

Myopathy can, rarely, present acutely or with acute complications. Examples include:

• Respiratory difficulties:
  • Respiratory failure can occur in a number of the myopathies
  • Aspiration pneumonia may be associated with this
  • Cardiac complications may be associated including cardiomyopathy and conduction defects
• Some metabolic myopathies:
  • Hypokalaemia:
    • Oral supplements
    • Cautious use of IV potassium
    • Prophylactic drugs (spironolactone and acetazolamide)
  • Hyperkalaemia:
    • Carbohydrate loading (for example early in attacks with hyperkalaemic periodic paralysis)
    • Glucose and insulin
• Rhabdomyolysis:
  • Causes life threatening renal complications and associated metabolic problems (hyperkalaemia)
  • Usually requires intensive care management
• Polymyalgia rheumatica:
  • Treatment with corticosteroids
  • Be aware of associated temporal arteritis

Long-term care

• Myopathy associated with respiratory failure:
  • Monitor pulmonary function (early restrictive pattern may occur before onset of symptoms)
  • Beware of symptoms of nocturnal hypoxia (poor sleep, nightmares, headaches)
  • Physiotherapy
  • May require tracheostomy and permanent ventilation
• Specific medication may be useful in particular situations for particular myopathies
• Genetic counselling
• Surgery:
  • Tendon release surgery, for example to prolong ability to walk
• Physical aids:
  • Walking aids
  • Wheelchairs
  • Adaptive devices
• Family support
• Dietary advice
  • General, for example to prevent obesity
  • Specific

• Respiratory failure
• Aspiration pneumonia
• Musculoskeletal problems:
  • Many associated deformities can occur
  • Joint contractures
  • Chest deformities
  • Spinal deformities including scoliosis
• Malignant hyperthermia can occur with central core disease

This depends on the specific diagnosis. The primary disorders are incurable conditions with varied prognosis. Secondary myopathy may be corrected by treating the underlying cause.

Genetic counselling is, in some of the most common myopathies such as DMD, the only intervention that can prevent disease. In general:

• Give genetic counselling early
• Test early for carrier status where appropriate
• Consider prenatal diagnostic testing where appropriate
• Advances in molecular genetics may help in the future