Myopathy (Muscle diseases)




Please start with the section on neuromuscular disease patterns for an introduction. Once you determined that the patient likely has a myopathy you will need to consider which type of myopathy to narrow down the differential diagnosis.

Clinical features of myopathy:

  • Muscle may be normal, wasted or pseudohypertrophied, depending on the disease and time of presentation
  • Weakness, usually more proximal than distal
  • Usually proximal rather than distal weakness, but there are distal myopathies. Also, some myopathies are restricted to certain muscle groups e.g. ocular and pharygeal muscles
  • Usually symmetric weakness
  • Pure motor weakness without sensory signs
  • Tendon reflexes are usually preseved until late in the disease. They may be depressed later on in the disease. Normal abdominal and plantar reflexes
  • Make an attempt to characterize which muscle groups are affected: upper limb shoulders girdle (deltoids,  rotator cuff), lower limb girdle (gluteal, quadreceps), distal muscles (finger flexors, peroneal muscles), occular muscles, pharyngeal muscles, diaphgram or heart.
  • Bowel and bladder sphincters are usually spared.

Firstly history and physical examination:

  • Onset/temporal features
  • Body part:
    • Ocular
    • Bulbar
    • Oesophageal, smooth muscle
    • Cardiac
    • Respiratory
    • Limbs:
      • Upper vs. lower
      • Proximal vs. distal
  • Associated features:
    • Cramps
    • Muscle pain at rest
    • Muscle pain on exercise
    • Exercise intolerance
  • Family history
  • Associated medical conditions: connective tissue diseases etc
  • Review medication list


Investigations to consider:

Blood tests:

  • Electrolytes: K+, Ca++, Mg++, PO3-
  • TFTs
  • Muscle enzymes: CK, LDH
  • Other muscle enzymes: glutamic oxaloacetic and glutamate pyruvate transaminases, aldolase

Urinalysis for myoglobin

  • Normal SNAP
  • Normal CMAP, unless severe distal myopathy is present, then reduced amplitude may occur.
  • Normal distal latency
  • Normal conduction velocity

EMG, myopathic:

  • Spontaneously: increased activity with fibrillations, complex repetitive discharges CRD and positive sharp waves PSW
  • On activation: Short duration, low amplitude polyphasic MUAP
  • Early recruitment
  • Nerve conduction studies: to exclude radiculoneuropathy

Muscle biopsy
Myositis and myopathy antibodies:

  • Necrotizing autoimmune myopathy: Anti-HMGCR Abs (3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase)
  • Myositis specific antibodies: Anti-Jo1, anti-Mi-2, anti-SRP,
  • Myositis associated antibodies: anti-RoRNP, anti-UiRNP, anti-PM/Scl, anti-ku



Causes of myopathy:

Muscular dystrophy:

Congenital myopathies (non-dystrophic congenital myopathies):

  • Nemaline myopathy
  • Central core disease
  • Centronuclear myopathy a.k.a. myotubular myopathy

Inflammatory myopathy:

Drug induced myopathies:

  • True myositis: Penicillamine, Procainamide
  • Zidovudine (a form of mitochondrial myopathy)
  • Glucocorticoids
  • Statins
  • Fibrates: Clofibrate
  • Chloroquine neuromyopathy
  • Hypokalaemic drugs (dyskalemic myopathy)

Endorine myopathy:

  • Cushing’s syndrome
  • Hyper or hypo- thyroidism
  • Hyper- or hypo- parathyroidism

Metabolic myopathy:


  • Parasitic polymyositis:
    • Toxoplasma, Trypanosoma, Cysticerci, Trichinae
  • Pyomyositis a.k.a. Tropical polymyositis:
    • Staphylococcus aureus, Streptococcus, Yersinia
  • Other bacteria:
    • Borrelia burgdorferi ‘Lyme disease’
    • Legionella pneumophila ‘Legionnaire’s disease’
  • Viral myositis:
    • Influenza, Coxsackie B virus
    • AIDS myopathy


Causes of Polymyositis:


  • Zidovudine
  • Penicillinamine
  • Overlap syndrome with other connective tissue disease

DDx. of polymyositis:

Chronic weakness:

Acute weakness:

  • Alcoholism
  • Neuropathy
  • Some Glycogen storage diseases
  • Parasitic polymyositis
  • Pyomyositis a.k.a. Tropical polymyositis
  • Other bacteria:
    • Borrelia burgdorferi ‘Lyme disease’
    • Legionella pneumophila ‘Legionnaire’s disease’
  • Pain and muscle tenderness:
    • Polymyalgia rheumatica
    • Fibromyalgia
    • Chronic fatigue syndrome

Causes of dermatomyositis:


  • Neoplasia in 15%:
  • Ovarian, breast, melanoma, colon cancer
  • Penicillinamine
  • Overlap syndrome with other connective tissue disease
  • Associates vasculitis in children

Causes of rhabdomyolysis:

  • Direct muscle injury:
    • Falls with immobility
    • Severe trauma or crush injuries
    • Prolonged surgical procedures
    • Severe physical exertion
    • Severe dehydration
    • Extremes of body temperature
  • Status epilepticus
  • Hypophostphataemia
  • Drugs:
    • Cocaine, amphetamines, statins, heroin, or PCP
  • Ischemia or infarction of muscle tissue
  • Some hereditary myopathies

Causes of raised CK (hyperCKaemia, raised creatine kinase):


Causes of myopathy with normal CK

  • Endocrine myopathies (except hypothyroidism):
    • Hyperthyroidism
    • Hypoparathyroidism
    • Hyperparathyroidism
    • Adrenal insufficiency
    • Acromegaly
  • Corticosteroid myopathy (Steroid induce myopathy)

Muscle pain on exertion:

Exercise induced exercise intolerance, cramps and increased CK:

  • Glycogenolysis defects:
    • Myophosphorylase MPH
    • Phosphorylase kinase PHK
  • Glycolysis:
    • Phosphofructokinase PFK

Causes of endoneurial lymphocytes:

  • Vasculitic neuropathy
  • Guillain Barre syndrome GBS
  • Chronic inflammatory demyelinating polyradiculopathy CIDP
  • Diabetic neuropathy
  • Normal