Leg Cramps

Leg cramps are involuntary, localised, and painful skeletal muscle contractions that originate in the peripheral nerves. Leg cramps typically occur at night and last only seconds to minutes.

Epidemiology

Approximately 7.3% of children complain of new onset nocturnal leg cramps each year. 3 , and around one third of the general population experience rest cramps, with 83% occurring in the leg and 73% occurring at night. 5 It is more common with increasing age with half of patients older than 64 years having leg cramps 1 Risk factors other than age include sport participation, hepatic cirrhosis, venous insufficiency, female gender, arthritis, and peripheral vascular disease.

Aetiology

• Idiopathic.
• Exercise-associated muscle fatigue.
• Medications
• Peripheral vascular disease.
• Venous insufficiency.
• Pregnancy.
• Uremia, end-stage renal disease.
• Cirrhosis.
• Hypokalemia, hypomagnesemia, hypocalcemia.
• Thyroid disease.
• Adrenal insufficiency.

Pathophysiology

Exercise-associated muscle cramps are due to altered neuromuscular control from muscular fatigue. 18 Nociceptive stimulation of myofascial trigger points has been shown to induce muscle cramps. 6 Hypokalemia and hyponatremia lead to muscle pain because of dysfunction of the Na+/K+/ATPase pump, which leads to sustained contraction of muscle fibers. Hypocalcemia causes increased excitation of nerve and muscle cells, causing cramping and even tetany. Hypomagnesemia impairs parathyroid hormone secretion with consequent hypocalcemia, which leads to cramps as described above.

Differential Diagnosis

• Myalgia - Muscle pain without contraction
• Occupational contraction - Agonist and antagonist muscles fire simultaneously; eg, writer's cramp
• Claudication - Abnormal circulation, abnormal Ankle Brachial Index
• Lower motor neuron disorders such amyotrophic lateral sclerosis or postpolio syndrome - Muscle wasting and weakness with abnormal electromyelogram result
• Restless leg syndrome - Unpleasant sensation in limbs requiring voluntary movement to relieve symptoms
• Muscle contractures - Occurs only during exercise, not after; specific for muscle glycolytic metabolism disorders

Clinical Features

Leg cramps are characterized by the acute, rapid onset of muscle spasms, accompanied by pain. A systematic review found that the most common diagnostic characteristics of leg cramps included intense pain, duration from seconds to 10 minutes, pain in the calf or foot, persistent pain after the cramp, and sleep disruption and stress. 33 Patients may have recently engaged in higher levels of physical activity or have a recent history of dehydration or acute volume depletion due to perspiration, diarrhea, vomiting, or diuretic use. If weakness is present, consider an underlying metabolic or neurologic disorder. If leg swelling or induration is present, consider an underlying infection, trauma, or ischemia. Many medications have been reported to cause cramps including corticosteroids, beta-agonists, beta-blockers, lithium, diuretics, statins, raloxifene, risedronate, donepezil, tolcapone, nifedipine, and albuterol. However, in a cross-sectional study of 365 elderly patients, no causal association was found for any class of drug, including diuretics. 1 Approximately two thirds of patients about to undergo hemodialysis and approximately 80% of patients on long-term hemodialysis complain of muscle cramps. 11

Investigations

Laboratory testing is generally used to identify the presence of metabolic causes of muscle cramps: electrolytes, calcium, magnesium, and renal function. In athletes, no measurable electrolyte or fluid status has been shown to cause exercise-associated muscle cramps. 20 In patients on dialysis, those with hyperphosphatemia were more likely to have cramps (odds ratio [OR] = 1.2; 95% CI, 1.1-1.5), while those with low parathyroid hormone levels were less likely to have cramps (OR = 0.8; 0.6-0.9). 11 If the leg is indurated or edematous, order an ultrasound to rule out deep vein thrombosis.

Diagnosis

Perform a thorough evaluation of medications as a potential cause. If the leg cramps are associated with increased physical exertion from baseline, they are likely exercise-associated muscle cramps. If cramping occurs along with other neurologic symptoms (eg, paresthesias, weakness) consider underlying neurologic or metabolic disorder. Perform a limited laboratory workup: electrolytes, calcium, magnesium, and renal function.

Treatment

Quinine is effective in treating leg cramps, but severe adverse reactions have been reported and most preparations have been banned by the FDA. A 27 Patients undergoing hemodialysis should receive creatine monophosphate before dialysis sessions to decrease the frequency of leg cramps. B 9 Patients undergoing hemodialysis should have tailored dialysate sodium concentration to decrease leg cramps. B 14 Pycnogenol decreases the frequency of nocturnal leg cramps. B 16 Diltiazem and verapamil are effective alternatives to quinine for treating leg cramps. B 12 22 B-complex vitamins are effective in treating nocturnal leg cramps in the elderly. B 15 Magnesium may be effective in treating leg cramps in pregnant women but not in non-pregnant adults. B 10

Medications

Quinine

In a systematic review of cross-over studies, patients who took quinine (200-300 mg at bedtime) had 3.6 fewer cramps (95% CI, 2.2-5.0) in a 4-week period than patients who took placebo; approximately 3% of the patients who took quinine experienced troublesome tinnitus. 27 A Cochrane review found 23 trials with 1586 participants of quinine. Notably, more than half of the patients in these trials came from 5 unpublished studies. The dose was typically 300 mg, and 20 trials included a placebo arm. Quinine was effective, reducing the number of cramps in a 2 week period by 28%, and the number of days with cramps by 20%. 30 Other studies have reported rare but serious side effects associated with quinine use including pancytopenia, hepatitis, hemolytic uremic syndrome, blindness, and coagulopathy. 23 24 25 26 The Cochrane systematic review estimated the risk of thrombocytopenia at 0.12% based on the observed RCTs. 30The FDA has banned most over-the-counter and prescription formulations of quinine.

Magnesium

Magnesium citrate did not reduce the frequency of nocturnal leg cramps in patients with nocturnal leg cramps in the ambulatory setting in a small crossover trial. 17A Cochrane review of magnesium supplementation identified 11 studies with 735 patients. There was no difference in number or severity of cramps in populations of older adults. 35 A single well designed randomized trial of 94 patients, mean age 65 years, with nocturnal leg cramps at least 4 times during a 2 week run-in period assigned them to magnesium oxide (520 mg elemental Mg+) at bedtime or placebo. While cramps were halved in both groups, there was no difference between groups. 31

Other medications

Patients given creatine monophosphate (12 mg orally) before dialysis sessions reported decreased frequency of leg cramps from 6.2 per week to 2.6 per week, while those given placebo reported no change (P < .05). 9 In a randomized trial of 53 patients undergoing 381 hemodialysis sessions, only 1 patient who received varying sodium concentrations in the dialysate complained of muscle cramps during dialysis compared with 10 patients receiving customary dialysates (NNT = 24; 95% CI, 13-106). 14 In a small cross-over trial, patients receiving diltiazem hydrochloride 30 mg at bedtime had fewer leg cramps (0.16-5.84 fewer cramps) than when they were taking placebo (P = .04). 12 In a tiny open-label study of 8 elderly patients with leg cramps despite quinine therapy, 7 of the patients treated with verapamil (120 mg at bedtime) reported that their leg cramps had resolved after 2 weeks. 22

Complementary/Alternative Therapy

Nearly 90% of elderly hypertensive patients with nocturnal leg cramps had remission of symptoms after 3 months of taking vitamin B complex (fursultiamine 50 mg, hydroxocobalamin 250 micrograms, pyridoxal phosphate 30 mg, and riboflavin 5 mg) 3 times daily compared with patients taking placebo who reported no change in symptoms. Additionally, the severity of symptoms in the B-complex group were reduced compared with those of the placebo group (2.6 vs. 8.2 on a 10-point scale). 15 In a nonrandomized study of patients with leg cramps taking a French maritime pine bark extract Pycnogenol, 200 mg daily), the frequency of leg cramps in healthy patients went from 5 events to 1 event per week, while patients taking a placebo had no response. 16 No studies of sufficent quality have reported benefit of non-drug therapies such as muscle stretching. 28

Physical Therapy

In a randomized trial with 191 patients, calf-stretching exercises did not decrease nocturnal leg cramps. 32 8 Overall the evidence regarding non-drug therapies for leg cramps is poor. 34

Pregnancy

A Cochrane identified five studies with pregnant 408 participants. One had positive findings, with approximately one third of pregnant women taking magnesium (citrate or lactate; 5 mmol in the morning and 10 mmol in the evening) having resolution of leg cramps compared with approximately 5% of women taking placebo (NNT = 4; 95% CI, 3-13). Other trials had mixed results or found no benefit. 35 There is no benefit to calcium and only a slight benefit to sodium (which can theoretically increase the blood pressure). 10 Fifteen of 21 pregnant women taking thiamine 100 mg plus pyridoxine 40 mg daily had complete resolution of leg cramps compared with only 2 of 21 women taking placebo (NNT = 2; 95% CI, 1-3). 21

Prognosis

Leg cramps are a painful nuisance that is not directly associated with long-term sequelae

Summary

The patient's medications should be reviewed carefully because they are a common cause of leg cramps. C Quinine is effective in treating leg cramps, but severe adverse reactions have been reported and most preparations have been banned by the FDA. A Diltiazem and verapamil are effective alternatives to quinine for treating leg cramps. B Vitamin B complex is effective in treating nocturnal leg cramps in the elderly. B Magnesium is effective in treating leg cramps in pregnant women but not in non-pregnant adults.

Literature Review

Literature Review

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