True muscle cramping represents motor unit hyperactivity leading to prolonged, involuntary muscle contraction. Precipitants include unopposed contraction, electrolyte and volume shifts, and lower motor neuron disease. Ordinary cramps most commonly occur in the gastrocnemius muscle and the intrinsic muscles of the sole of the foot. Their nocturnal predilection appears to be related to unopposed plantar flexion of the foot in bed, which places the muscles of the calves and feet in their most shortened and therefore most vulnerable position. Without modulation by opposing muscles, the sustained contraction produces the characteristic nocturnal leg cramp, which is experienced as sudden, severe calf pain; often, the muscle is palpable or visibly hardened. In many instances, a voluntary contraction triggers the cramp. Passive stretching relieves it.

True cramps may be precipitated by volume and electrolyte shifts, which account for the fact that they frequently occur during hemodialysis and can be relieved with the administration of hypertonic dextrose. Heat cramps that occur during activity are a consequence of dehydration and sodium loss and respond to replenishment. Hyponatremia is a consistent feature of fluidbased muscle cramps. In marathon runners who suffer severe cramps, the hyponatremia can be severe, resulting from the combination of salt depletion and the drinking of large volumes of free water. Contrary to common belief, hypokalemia is not a clearly established precipitant of true muscle cramps; cramps attributable to potassium-wasting diuretics are actually uncommon and may be related to salt depletion. Ordinary cramps are often a part of symptomatic hypoglycemia. Muscle cramps are sometimes drug or dietary supplement induced, as may occasionally occur with nifedipine, β-agonists, alcohol excess, and use of bodybuilding supplements containing excessive concentrations of selenium and chromium.

The cramp is a neural or electrical phenomenon, not primarily muscular. Electromyography shows fasciculations preceding the cramp. Cramps accompanied by clinically evident fasciculations are characteristic of lower motor neuron diseases, such as polio in the recovery phase, peripheral nerve injury, nerve root compression, and amyotrophic lateral sclerosis.

Contractures also represent involuntary muscle contractions, but they are electrically silent and characteristically occur during exertion, not rest. They develop in persons who have inherited metabolic defects that impair the formation of adenosine triphosphate, which is needed for muscle relaxation. Most patients have McArdle disease. Both hyperthyroid and hypothyroid disease may cause cramping. Exertional cramping has been seen in hyperthyroidism. In hypothyroidism, impaired muscle relaxation produces the “hung-up” reflexes that characterize the condition.

Tetany is a state of both motor and sensory hyperactivity associated with muscle spasm and paresthesias. The muscles of the mouth, hands, and lower extremities are typically involved, and carpopedal spasm is a characteristic manifestation, as are Chvostek and Trousseau signs. Hypocalcemia, hypomagnesemia, respiratory alkalosis, and hypokalemia are known precipitants. In severe cases, seizures may ensue if the condition goes uncorrected.

Occupational cramp is a form of dystonia in which muscle contractures occur in persons engaging in fine motor activities that have taken years to perfect. The typical patient is a writer or pianist whose hands curl involuntarily when he or she attempts to write or play.

Patients may report cramp-like symptoms in the context of important medical conditions, including peripheral arterial insufficiency, restless leg syndrome, and statin-associated muscle injury. Autoimmune forms of myositis (dermatomyositis, polymyositis) usually present as proximal muscle weakness and possibly some soreness in the proximal muscles, but cramping is not part of the clinical picture.