History and exam

Key diagnostic factors

common

concurrent hemodialysis (organic cause)

Intradialytic cramps have been reported in 15% to 87% of patients undergoing hemodialysis support, particularly when ultrafiltration rates are high to remove excess fluid.[18][19][20][21][22]

cirrhosis (organic cause)

Cramps have been reported in 22% to 88% of patients with cirrhosis.[23][24][25][26][27]

pregnancy (idiopathic cramp)

A significant risk factor for cramps.[35]

strenuous exercise (idiopathic cramp)

Particularly in endurance events, such as the triathlon, marathon, and ultramarathon.[28][29][30]

medication use (idiopathic cramp)

Use of statins, imatinib, and beta-blockers with intrinsic sympathomimetic activity are the most common medications associated with muscle cramps.

nocturnal onset (idiopathic cramp)

Cramps occurring only during sleep are usually idiopathic cramps (benign or ordinary).[3]

gastrocnemius muscle involvement, with or without foot involvement (idiopathic cramp)

Cramps involving only these muscles are more likely to be idiopathic cramps (benign or ordinary).[13]

duration <10 minutes (idiopathic cramp)

After an explosive onset, idiopathic cramps will last from seconds to minutes.​[1][9][10][13][16]​​

unilateral (idiopathic cramp)

Idiopathic cramps are always unilateral (organic causes produce unilateral or bilateral symptoms).

precipitation by both trivial movements and forceful contractions (idiopathic cramp)

Finding in idiopathic cramps.

visible or palpable muscular knotting

Finding in all cramps.

good response to passive/active stretching (idiopathic cramp)

If the cramp does not respond to passive/active stretching, organic associations or differential diagnoses need to be considered.

normal neurologic exam (idiopathic cramp)

Common with idiopathic cramps.

normal general physical exam (idiopathic cramp)

Typically, no abnormal findings on exam in people with idiopathic cramp.

uncommon

other local muscle involvement (neuromuscular disease cramp)

Local cramps in muscles other than the gastrocnemius or foot are frequently noted in the context of neuromuscular disease.[1]

widespread muscle cramps (lower motor neuron disease)

Widespread cramps, particularly when associated with muscle weakness, suggest lower motor neuron disease (e.g. amyotrophic lateral sclerosis).

duration >10 minutes (organic cause)

Cramps lasting longer than 10 minutes (particularly in a child) suggest an organic cause.

abnormal neurologic exam (organic cause)

Neurologic abnormalities, such as sensory loss, hyperreflexia, and spasticity, point to organic etiologies of cramping disease.

abnormal musculoskeletal exam (organic cause)

Signs such as weakness, loss of muscle bulk, and continuous fasciculations (by direct visualization or palpation) point to organic etiologies of cramping disease.

Other diagnostic factors

uncommon

signs of a chronic medical condition (organic cause)

True cramp may be associated with various chronic medical conditions, including peripheral vascular disease, cardiovascular disease, hypokalemia, neurologic disease or deficit, arthritis, and gastritis, and there may be associated signs or symptoms.

Hypothyroidism (and much less frequently, hyperthyroidism) predisposes to cramps.

Various familial disorders may be suspected by their typical signs and symptoms.

Risk factors

strong

pregnancy

A significant risk factor for cramps.[35]

The underlying cause of pregnancy-related cramps is unknown.

Hypomagnesemia has been suggested to play a role in etiology.[36]

Hyperphosphatemia is not causative.[37][38]

Delivery ameliorates pregnancy-related cramps.[17]

strenuous exercise

Particularly in endurance events, such as the triathlon, marathon, and ultramarathon.[28][29][30]

Team sports (e.g., American football) also predispose to exercise-associated muscle cramps (EAMC).[28][30]

Various hypotheses for EAMC have been suggested but have not been proven.[39][40] There may be different types of EAMC that are initiated by different mechanisms.[30]

Risk factors for EAMC in marathon runners include older age, longer running history, higher BMI, shorter daily stretching time, irregular stretching habits, and a positive family history of cramps.[40] Other risk factors in marathon runners and triathletes include high-intensity running, long-duration running (>30 km), subjective muscle fatigue, and hill running.[40][41]

For athletes in general, the most important risk factors include a past history of EAMC, increased exercise intensity by race pace or subjective assessment (intrinsic factors), and increased environmental temperature and humidity (extrinsic factors).[28] All lead to premature muscle fatigue.

Muscles most frequently affected include force-generating biarticular muscles (e.g., the triceps surae, hamstrings, and quadriceps).[42]

hemodialysis

Intradialytic cramps have been reported in 15% to 87% of patients undergoing hemodialysis support.[18][19][20][21][22]

Hyperphosphatemia enhances cramp risk in patients undergoing hemodialysis.[20]

Although data are scant, the frequency of cramps in patients undergoing peritoneal dialysis is said to be similar to that in hemodialysis recipients.[20]

There is some evidence to suggest a correlation between free serum leptin concentrations and frequency of intradialytic cramps.[43]

cirrhosis

Cramps have been reported in 22% to 88% of patients with cirrhosis.[23][24][25][26][27]

Clinically relevant cramps (defined as those occurring at least once weekly, negatively affecting the patient's quality of life, and requiring analgesia) were reported in 12% to 42% of these patients.[24][25][26][27][44] Cramps are a major cause of the poor quality of life experienced by patients with cirrhosis.[45][46]

The prevalence of cramp is higher in patients with cirrhosis than in patients with noncirrhotic liver disease.[27]

There is a significantly higher frequency of finger and thigh cramps compared with that reported by control subjects and people with chronic noncirrhotic liver disease.[25]

Diuretic use has not been found to be a causative or a contributing factor to cramps in people with cirrhosis.[24][25][26][27]

use of imatinib

Tyrosine kinase inhibitors (TKIs), such as imatinib, are a class of medication used for certain types of cancer. Imatinib was reported to cause cramps in up to 50% of patients, with the frequency increasing when doses of >750 mg/day were used.[47]​ Cramps usually occur in the hands, feet, calves, and thighs.[48] Skeletal muscle toxicity including muscle cramps has been associated with all TKIs​.[49]

use of beta-blockers with intrinsic sympathomimetic activity

Beta-blockers with intrinsic sympathomimetic activity (e.g., pindolol, carteolol) cause cramps in a significant proportion of recipients.[50][51]

weak

age >60 years

Idiopathic (ordinary) cramps are most frequently seen in older people.[3]

The aging process is a theoretical risk factor.[52] Aging has mostly been reported to increase the incidence of cramps, although some studies have found no effect.[9][11]​​[14]​​

A sedentary lifestyle has been associated with nocturnal leg cramps in patients over 60 years.[53]

female sex

Most epidemiologic trials have found that women are more predisposed to cramps than men, regardless of age, in a ratio of about 3:2.[10][11]​​[14]​​

family history of cramp

Certain genetic syndromes are associated with cramps.

Familial muscle contraction syndromes include Kocher-Debre-Semelaigne, muscular dystrophies (such as Becker, limb-girdle type 1c, or Brody disease), congenital myotonia, glycogen storage disease (such as McArdle disease), Isaac disease, Satoyoshi syndrome, Schwartz-Jampel syndrome, and autosomal dominant cramps.

use of statins

Statins cause myopathy (a combination of myalgias, weakness, and cramping) in a small proportion of recipients (1% to 10%), especially when combined with fibrate therapy (e.g., gemfibrozil) or used in high doses.[54]

Cramps have been anecdotally related to statin use, but there are scant data linking statins to this effect.[55]

However, in one epidemiologic trial, cramps were noted in 20/338 (6%) of statin recipients.[56]

Cramps alone occur in a vanishingly small proportion of cases of statin myopathy.

use of other agents that may cause muscle cramps

Numerous agents have been suggested to be implicated in the development of cramps. However, most supportive data are weak, consisting of case reports or series.

Examples include antihypertensives (e.g., diuretics, ACE inhibitors, calcium-channel blockers), lipid-lowering agents (e.g., fibrates, niacin), beta-agonists (e.g., albuterol, terbutaline), corticosteroids (e.g., prednisone, beclomethasone), non-corticosteroid hormonally active drugs (e.g., medroxyprogesterone, testosterone, estrogens, progesterone, insulin, teriparatide, raloxifene), others (e.g., methimazole, cisplatin, oxaliplatin, penicillamine, phenothiazines, pyrazinamide, zolmitriptan), opioid withdrawal or alcohol consumption, and bowel cleansing agents (e.g., sodium phosphate).[5][57][58][59][60][61][62][63][64][65][66][67][68][69][70][71][72][73]

hypoglycemia in patients with diabetes mellitus

Case series have demonstrated a relationship between hypoglycemia in patients with diabetes mellitus and the emergence of cramps.[64][74]​​[75]

Cramps have been traced to the presence of risk factors for hypoglycemia several hours before the episode (e.g., alcohol consumption, prolonged abstinence from food, excessive activity without compensatory dietary changes, excessive doses of antidiabetic medication). Thus, cramps are prominent 3 to 5 hours after going to bed and several hours after a meal.

Cramps occur together with other symptoms and signs of hypoglycemia (intense hunger, tremor, profuse sweating, tachycardia, mental clouding). These all respond rapidly to correction of the hypoglycemic state.

chronic diseases

Various chronic medical conditions have been found to be associated with muscle cramps (e.g., peripheral vascular disease, cardiovascular disease, hypokalemia, neurologic disease or deficit, arthritis, and gastritis).[8][10][11]​​[76]​​

Hypothyroidism (and, much less frequently, hyperthyroidism) predisposes to cramps.

home parenteral nutrition

About one quarter of patients maintained on home parenteral nutrition report muscle cramps directly related to feedings and may require a slowing of the feeding rate, or pharmacologic therapy.[77]

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