Aetiology

True muscle cramps are commonly idiopathic. They may also be associated with:[3]

  • Pregnancy

  • Strenuous exercise

  • Haemodialysis

  • Cirrhosis

  • Other chronic diseases

  • Metabolic or electrolyte disturbances

  • Certain drugs (strongest association with imatinib, beta-blockers with intrinsic sympathomimetic activity, and statins).

They are believed to be of neural origin.[2][3]​​[16][31]​​

Pathophysiology

On an electromyogram, cramping is associated with repetitive firing of motor unit action potentials at high-frequency rates (up to 150/second).[16] The number of motor units activated and the frequency of their discharges increase gradually during the cramp and then subside gradually, with an irregular firing pattern towards the end. This painful, involuntary muscle contraction associated with electrical activity is termed a true cramp. Several lines of evidence suggest that true muscle cramps arise from spontaneous discharges of motor neurons rather than from within the muscle fibres themselves.[16][32] Another issue is whether high-frequency discharges arise in the central nervous system (CNS) or are spontaneously generated in the peripheral nervous system. Available data support both possibilities, although most data indicate a peripheral origin.[32] Although findings to date cannot exclude the possibility of a CNS influence on cramps (perhaps by increasing or decreasing cramp thresholds in a given peripheral nerve), it is reasonably clear that peripheral nerve and/or neuromuscular junction sites are most important.[33][34]

Classification

Based on clinical and electromyographical differences[4]

True cramp (motor unit hyperactivity):

  • Idiopathic cramp

  • Lower motor neuron disease

  • Haemodialysis cramp

  • Heat cramp

  • Fluid- and electrolyte-related

  • Drug-induced cramp.

Contracture (electrically silent):

  • Metabolic myopathy

  • McArdle's disease

  • Thyroid disease.

Tetany (sensory and motor unit hyperactivity):

  • Hypocalcaemia

  • Respiratory alkalosis

  • Hypomagnesaemia

  • Hypokalaemia

  • Hyperkalaemia.

Dystonia (simultaneous contraction of agonist and antagonist muscles):

  • Occupational cramp

  • Drug-induced cramp.

Based primarily on clinical criteria and pathogenesis[5]

Paraphysiological:

  • Occasional cramps

  • Cramps during sporting activity

  • Cramps during pregnancy.

Idiopathic:

  • Familial

  • Sporadic

  • Others.

Symptomatic cramps:

  • Central and peripheral nervous system diseases

  • Muscular diseases

  • Cardiovascular diseases

  • Endocrine-metabolic disease

  • Hydroelectrolyte disorders

  • Toxic and pharmacological disorders

  • Psychiatric disorders.

Based on alleged origin[6]

Muscle origin:

  • Contracture

  • Myotonia.

Nerve origin:

  • Neuromyotonia

  • Tetany

  • Idiopathic muscle cramps.

Central origin:

  • Tetanus

  • Stiff-man syndrome.

Based on pathogenesis[7]

Myogenic disorders, disorders of motor neuron or peripheral nerves:

  • True (idiopathic) cramps

  • Benign fasciculation and cramps

  • Tetany

  • Multiple sclerosis

  • Isaac's syndrome

  • Myokymia.

Central disorders:

  • Stiff-man syndrome

  • Occupational cramps.

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