Sleep-related leg cramps …

Jiri Nepozitek MD PhD

Sleep Disorders

Updated 08.09.2024
Released 08.17.1995
Expires For CME 08.09.2027

Sleep-related leg cramps

Author: Jiri Nepozitek MD PhD

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Editor: Federica Provini MD

Sleep-related leg cramps

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Introduction

Overview

Sleep-related leg cramps are a sleep-related movement disorder whereby painful contractions of the calf or foot muscles arise during time in bed and may interrupt sleep and worsen quality of life. They may be associated with muscle cramps during daytime wakefulness. Sleep-related leg cramps are encountered at all ages, but they are especially prevalent among the elderly. They may result from a variety of pathologies, metabolic muscle and nerve disorders, electrolyte disturbances, vascular diseases, neurologic disorders such as Parkinson disease, and toxic and drug side effects. Sleep-related leg cramps may sometimes mimic and need to be differentiated from other sleep-related movement disorders, especially the manifestations of restless legs syndrome.

Key points

	• Sleep-related leg cramps represent a common sleep-related movement disorder characterized by painful contractions of the muscles of the lower limbs during sleep.
	• This disorder can be either idiopathic or secondary to metabolic, vascular, or neurologic diseases or medications.
	• Diagnosis is clinical and requires exclusion of secondary forms; polysomnography may be helpful to rule out other conditions.
	• Treatment comprises nonpharmacological and pharmacological therapies.

Historical note and terminology

According to the American Academy of Sleep Medicine International Classification of Sleep Disorders, sleep-related leg cramps, previously classified within the parasomnias and precisely as a wake-sleep transition disorder, fall within the category of the sleep-related movement disorders (03). Within this category, sleep-related leg cramps are grouped together with restless legs syndrome, periodic limb movement disorder, sleep-related bruxism, sleep-related rhythmic movement disorder, benign sleep myoclonus of infancy, propriospinal myoclonus at sleep onset, and sleep-related movement disorder either unspecified, due to drug or substance, or to a medical condition. Sleep-related movement disorders are conditions that are primarily characterized by relatively simple, usually stereotyped movements that disturb sleep or by other sleep-related monophasic movement disorders such as sleep-related leg cramps. Leg cramps may be sleep related when they occur solely or predominantly during sleep and idiopathic when they remain unassociated with any other disturbance. On the other hand, sleep-related leg cramps may be secondary to several systemic or focal pathologic conditions.

Clinical manifestations

Presentation and course

Sleep-related leg cramps are characterized by sudden and intense involuntary painful contractions of the muscles or muscle groups of the lower limbs, in particular those of the posterior compartment of the leg and foot; the triceps surae is the muscle group most frequently affected. The forceful contraction of these muscles is accompanied by immediate intense pain that awakens the patient and interrupts sleep. During the calf cramp, the muscles involved are firm and tender, and feet and toes are held in extreme plantar flexion. Cramps are usually unilateral and last from several seconds to minutes (1.7 minutes as a mean) (56); the cramps may remit spontaneously and are followed by a residual tenderness for up to half an hour. Patients quickly learn to lengthen the cramping muscle (by forcible dorsal flexion of the foot), and this maneuver is usually enough to stop the cramping. Sometimes, however, patients are forced to jump out of bed and stand or walk in order to get rid of the cramps. Nocturnal leg cramps may be accompanied, particularly when secondary to systemic illnesses, by muscle cramps during wakefulness. The frequency of muscle cramps varies considerably from less than yearly to multiple episodes every night, but they intensify with older age (81).

Prognosis and complications

Idiopathic sleep-related leg cramps are usually benign. When secondary, the prognosis of the cramps is that of the underlying systemic disorder. Idiopathic sleep-related leg cramps may remit spontaneously over time; however, they may also represent a longstanding complaint, especially in the elderly wherein 20% of patients report them for over 10 years (01). Patients who have already used drugs to treat their cramps in the past have a higher number of cramps per day (81).

Sleep-related leg cramps were shown to be associated with impaired quality of life, and the impairment is mediated through sleep disturbances (35; 82). Besides low quality of sleep, nocturnal leg cramps were reported in association with daytime sleepiness (28). In contradiction to these results, an observational study has not confirmed the link between intensity of nocturnal cramps and poor sleep quality (83).

Clinical vignette

A 41-year-old woman had a family history positive for nocturnal leg cramps in her 69-year-old father and three paternal aunts. Her 67-year-old mother had thyroid disease. As a child, the patient underwent three operations for strabismus of her left eye; she developed hypothyroidism at 37 years of age, which was well controlled with thyroxine, 100 mg per day. At 36 years of age, she noticed painful cramping sensations arising suddenly in thoracic and abdominal muscles, followed by local tenderness. Within a year these cramping sensations quickly spread to involve the lower limbs, especially during the evening and at night when she was lying in bed trying to fall asleep. During the cramps, which especially involved the calves and feet, the muscles felt firm and tender.

Neurologic examination disclosed sporadic fasciculations in calf and foot muscles. Serum and urine electrolytes, creatinine phosphokinase, and thyroid and parathyroid hormones were normal. EMG documented fasciculation potentials in the abductor hallucis and gastrocnemius muscles without denervation. Motor and sensory conduction velocities were all normal, and no pathologic EMG activity could be induced by hyperventilation or ischemia. Forceful prolonged voluntary plantar flexion of the toes and short-lasting tetanic stimulation (10 Hz for 1 second) of the tibial nerve at the ankle readily evoked cramping in the abductor hallucis, which was relieved by stretching of the big toe. Polysomnographic recordings disclosed cramps in the plantar flexor muscles (more evident on the right), which lasted 18 to 25 seconds and slowly resolved by extension of foot and toes. Sleep structure was normal.

Administration of vitamin D, calcium, magnesium, gabapentin, and benzodiazepines was unsuccessful. The patient obtained partial relief with carbamazepine, 600 mg per day.

Biological basis

Etiology and pathogenesis

Sleep-related leg cramps may be either idiopathic or related to other diseases or drugs; however, no significant differences in clinical presentation due to a specific etiology have been evidenced.

Sleep-related leg cramps occur rarely in children, when they remain, for the most part, idiopathic. No systemic illnesses are typically present. Metabolic and hormonal disorders such as muscle glycogenosis, hypothyroidism and hypoparathyroidism, diabetes mellitus, and fluid and electrolyte disturbances (hypocalcemia, hypomagnesemia, hyponatremia, and uremia) are associated with cramps that may occur predominantly or exclusively during sleep. Such conditions as low levels of minerals, extracellular fluid volume depletion, and sedentary activity have been noted as potential contributing factors in elderly patients (66; 02; 81). In addition, the use of medications such as diuretics and long-acting beta2 agonists may be related to leg cramps (27). Spasticity and rigidity, peripheral neuropathy, and vascular insufficiency of the lower limbs represent conditions with an increased prevalence of sleep-related leg cramps. A study of 1788 patients with liver cirrhosis revealed a 51.8% prevalence of sleep-related leg cramps, thus, placing emphasis on assessing for this bothersome symptom in hepatic disease (43).

Cramps are contractions of muscles brought about by sustained recruitment of one muscle’s motor units. EMG studies show that cramping is attended by a contraction of a slowly moving fraction of muscle fibers with extremely short potentials and unlike maximal voluntary contraction (74). Explicative hypotheses implicate an abnormal excitability of the muscular membrane or of the terminal motor axon at the muscle entry point (motor point). Although some studies hypothesized a central origin of muscle cramps, due to an abnormal CNS drive acting on the lower motor neuron or increased fusal and decreased Golgi tendon organ activity, causing changes in presynaptic input and spinal motor neuron excitation (78), the peripheral theory remains more convincing (62; 71). Lower limb muscle weakness is suggestive of being a risk factor for the development of nocturnal leg cramps in the elderly, which was seen in a case-controlled study where the authors concluded that age-related modifications in type II muscular fibers may expose to higher risk of nocturnal cramps (35). Also, muscle and tendon shortening are suspected to take part in the increasing the risk of occurrence of nocturnal leg cramps according the “squatting theory” (87; 18). Lower limb muscle weakness as seen in a case-controlled study was suggestive of being a risk factor for the development of nocturnal leg cramps in the elderly (35). Repetitive stimulation of homonymous afferents and magnetic stimulation of the nerve trunk induce muscle cramps, whereas cutaneous stimulation and antidromic Renshaw cell activation are effective in curtailing the cramp (05). After discharge activity is typically found following M and F waves in patients with muscle cramps, suggesting impaired motor neuron excitability. Foot and leg muscles have different cramp susceptibility (63), and various frequencies of electrical stimulation trigger different sized cramps (64).

Sleep-related leg cramps may be observed throughout sleep stages 1, 2, and 3 NREM as well as REM sleep; therefore, they cannot be attributed to physiologic changes during any specific sleep state.

Sleep-related leg cramps may have a genetic basis. Familial nocturnal cramping of the legs associated with myoclonic jerks and leading to painful awakenings has been observed to recur in a three-generation family, transmitted in an autosomal dominant fashion (44). Muscle cramps both during sleep and wakefulness were associated with electromyographic findings suggestive of polyneuropathy with an autosomal dominant transmission in a Japanese family (14) and to neuropathic involvement in an Italian family (60).

Epidemiology

Sleep-related leg cramps may be encountered at all ages. Epidemiologic studies in children demonstrated that nocturnal leg cramps have an overall incidence of 7.3%; the incidence increased at 12 years of age, peaking between 16 and 18 years. Nocturnal leg cramps were, however, absent in children younger than 8 years of age. Seventy-three percent of the children had cramps only during sleep; the remainder also had cramps during wakefulness. Leg cramps were unilateral in nearly 99% of cases, occurring one to four times per year in the majority of children, and each episode lasted 1.7 minutes as a mean, leaving a residual tenderness for about half an hour (56).

Sleep-related leg cramps also are frequent among the general population. The incidence and prevalence increases with age (66; 25). In a general population survey conducted in 1987 in Sao Paulo, Brazil, leg cramps were reported by 2.6% of 1000 representative adult residents, especially females (males to females ratio 1:1.8), but increased to 5.8% in a later survey conducted in 1995 in the same population (68). No association was found between gender and prevalence of sleep-related leg cramps (57). In a survey of veteran outpatients, 56% reported nocturnal leg cramps. In this population, leg symptoms were often associated with hypertension, renal disease, hypokalemia, and vascular disease affecting the legs, heart, and brain. In another survey of male veterans, cardiovascular disease and peripheral neurologic defects were significantly higher in patients with nocturnal leg cramps; there was no relation with use of diuretic, beta-agonist, or calcium channel antagonist drugs (33; 02; 57). In 365 elderly patients over 65 years of age, leg cramps were found in 50%. Cramps were more prevalent at night in 62% of patients and remained a longstanding complaint, being present for over 10 years in 20% of cases. Again, an association with peripheral vascular disease and arthritis was found (01). In a cross-sectional study of 516 subjects over the age of 60 years in France, prevalence of nocturnal leg cramps was 46% (57).

Nocturnal leg cramps have been associated with several other physiologic and pathologic conditions (46):

	• Pregnancy: 30% to 81% of pregnant women experience nocturnal cramps, especially after the 25th week of pregnancy (39; 38). In this patient population, nocturnal leg cramps have been reported to occur together with restless legs syndrome (90).
	• Venous insufficiency and varicose veins of the lower limbs
	• Root disease of the lower limbs and “vespers’ curse,” a condition in which lumbar radiculopathy and spinal stenosis combine to cause nocturnal calf cramps, fasciculations, night pain, and paresthesias (61; 32).
	• Liver cirrhosis
	• Diabetes mellitus (in which patients with leg symptoms are usually younger and have earlier onset of diabetes)
	• Cancer
	• Parkinson disease (07)
	• Tropical ataxic neuropathy and tropical spastic paraparesis due to human T-cell lymphotropic virus type 2
	• Myokymia-cramp-fasciculation syndrome
	• Myofascial pain syndrome of the gastrocnemius muscle (70)
	• Myotonia and late-onset lipid storage myopathy
	• Electrolyte disturbances (especially hypokalemia and hypocalcemia) and sweat loss during sports, even though the evidence for the electrolyte disturbances actually causing the muscle cramps is controversial (79).
	• Thyroid dysfunction
	• Metabolic syndrome (58)
	• Uremia
	• Maintenance hemodialysis
	• Gitelman syndrome, a hereditary renal disorder with hypokalemia, hypomagnesemia, metabolic alkalosis, and hypocalciuria (23; 54).
	• Satoyoshi syndrome, characterized by progressive intermittent muscle spasms, alopecia, diarrhea, amenorrhea, and bony deformities (13).
	• Machado-Joseph disease (47; 17)
	• Anti-MAG neuropathy (72)

Sleep-related leg cramps are also known to complicate treatment with the following products: diuretics, beta2 agonists used as bronchodilators, statins (25), vincristine (where they signal early neurotoxicity), sodium oxybate used for narcolepsy (10), donepezil (76), oxcarbazepine for epilepsy (52), cholinesterase inhibitors, and hemodialysis for uremia. Statins, which are inhibitors of 3-OH-3 methylglutaryl coenzyme A reductase, used in lowering cholesterol blood levels, have been associated with persistent myalgias and muscle cramps with or without creatine kinase elevation, and even with rhabdomyolysis and muscle weakness. Cerivastatin seems the most implicated statin, but impaired hepatic and renal function, hypothyroidism, diabetes, and other concomitant medications seem to contribute to statin toxicity. Muscle pains and weakness may affect up to 5% of the patients using these drugs. The mechanisms of such statin-induced myopathy are still discussed; regulatory proteins involved in myocyte maintenance have been implicated (88). The pathophysiology of statin-induced myopathy and muscle symptoms is complex and involves mitochondrial dysfunction, disruption in calcium homeostasis, antibodies to HMG-CoA reductase, and other less well-defined mechanisms (73). Sleep-related leg cramps are also more common in patients with other sleep disturbances such as bruxism and sleep paralysis (67).

Management

Nonpharmacological therapy consists of stretching techniques, physical therapy, and regular physical activity.

Passive pre-sleep stretching techniques of the affected muscles, in particular forcible dorsal flexion of the toes and feet, are repeatedly reported to be potentially effective in reducing the frequency and intensity of the cramps (16; 31; 34; 30). In people over 55 years of age a combination of calf and hamstring stretching was shown to reduce the severity of night-time lower limb muscle cramps (36). Calf stretching alone may lead to little or no improvement in the frequency, and whether a combination of daily calf, quadriceps, and hamstring stretching reduces the frequency and severity is uncertain. Contradictory results, limited evidence, and biases of available studies limit the use of stretching techniques as treatment for leg muscle cramps (09; 24; 18). The strength of nonpharmacological therapy is the lack of side effects in contrast to most pharmacological treatment options; therefore, the stretching techniques offer a useful treatment alternative despite inconclusive evidence (30).

Regular physical activity is recommended, particularly in elderly adults because sedentary lifestyle was found to be strongly associated with nocturnal cramps in the group of individuals over 60 years (18).

Physical therapy measures for the patients with chronic nocturnal leg cramps have not been adequately studied so far. A case report of a single patient who received therapy focusing on muscle strengthening, joint mobility, soft tissue extensibility, and biomechanical influences during purposeful movement demonstrated improvements in pain and cramp duration, but the subject was still hesitant to perform certain tasks, possibly due to the lack of biopsychosocial interventions in the treatment plan (04).

Pharmacological treatment consists of withdrawal of offending drugs and treatment of the underlying causes. When this is effective and in mild cases, pharmacologic treatment may not be warranted. If sleep-related leg cramps severely disrupt quality of sleep and of life, drug treatment may be initiated.

Quinine sulphate. Quinine sulphate given orally at variable dosages (200 to 325 mg) before bedtime is significantly effective in reducing frequency (although seemingly not the severity or duration) of individual cramps as borne out by several randomized, double-blind, placebo-controlled studies and meta-analysis of efficacy (15; 59; 20; 92; 19). In elderly people, quinine reduced the number of nights with cramps by an average of 27.4% compared to placebo. A trial of 4 to 6 weeks of treatment with quinine has been recommended (12). Quinine has also been reported to be more effective when combined with theophylline in a single preparation. Quinine seems to act by decreasing the excitability of the motor end plate, thereby reducing the contractility of muscle fibers. Nevertheless, 200 mg of quinine at bedtime was ineffective in a double-blind, randomized, crossover trial (85). Quinine is significantly more effective than vitamin E; the latter at a dosage of 800 U at bedtime was shown to be ineffective compared to placebo in reducing leg cramps (15). Supplementation with vitamins E and C, however, was found significantly effective in the treatment of muscle cramps during hemodialysis (48; 29).

Quinine should be used cautiously and at the lowest dosage possible, especially in elderly people and in those with renal failure. Quinine should be avoided altogether during pregnancy and in liver disease. Quinine use is associated with increased side effects such as tinnitus, potentially fatal thrombocytopenia and hypersensitivity reactions, cutaneous photosensitivity and vasculitis, cortical renal necrosis (55), and granulomatous hepatitis. Quinine overdose, accidental or by self-poisoning, causes confusion, seizures, coma, and severe visual deficits, especially in older women, and may lead to death (11; 89). Therefore, a careful balance of the therapeutic gains and possible side effects of quinine should be made; in the elderly especially, treatment should be started with low incremental dosages and closely monitored by the attending physician. Use of tonic water or bitter lemon (commercial beverages containing quinine) for the purpose of curtailing nocturnal leg cramps should be discouraged (11). In conclusion, the use of quinine to treat legs cramps, especially in the elderly, is controversial, in particular considering the modest effect and the possible rare but serious adverse events (41; 71).

Other pharmacological treatments reported as effective are:

	• Verapamil hydrochloride 120 mg orally at bedtime
	• Rutosides given for nocturnal leg cramps associated with chronic venous insufficiency (69)
	• Gabapentin, which at 600 mg/day proved effective in a case of myokymia-cramp syndrome and gave a nearly total reduction of cramps after 3 months of therapy in 30 patients with longstanding muscle cramps (84)
	• The use of baclofen was reported to be effective for nocturnal calf cramps in individuals with lumbar spinal stenosis (50). The effectiveness and safety were comparable to gabapentin.
	• Although there is some evidence of a positive effect of magnesium (80; 06), other reports are conflicting (94; 26; 25; 71; 75).
	• Oral zinc sulphate (53) and branched-chain amino acid supplements (77) improved muscle cramps in cirrhotic patients.
	• Sleep-related leg cramps in patients with Parkinson disease respond to treatment with chronic release levodopa formulations (07).
	• In a group of 24 patients with nocturnal calf cramps, lidocaine injection at the gastrocnemius trigger point gave a significant reduction in all aspects of cramps (49), with an outcome better than quinine 300 mg orally (70). The block of the medial branch of the deep peroneal nerve by using lidocaine has been reported as having a positive effect in patients experiencing nocturnal leg cramps following lumbar spine surgery (42).
	• Likewise, botulinum injection into calf muscles significantly lowered patients’ cramping scores with a clinical benefit lasting about 3 months (08). Even axillary botulinum A injection was reported as effective in reducing muscle cramps associated with severe axillary sweating (22).
	• Other reports concern the use of diltiazem, a calcium channel antagonist, low-dose aspirin, and jackyakamcho-tang (shaoyaogancao-tang), a Chinese herbal preparation (45), for nocturnal leg cramps as well as l-carnitine, extracts of peony and licorice roots (40), vitamin K2 (93), and vitamin E (29) for muscle cramps associated with hemodialysis.

References

01: Abdulla AJ, Jones PW, Pearce VR. Leg cramps in the elderly: prevalence, drug and disease associations. Inta J Clin Pract 1999;53:494-6. PMID 10692732
02: Allen RE, Kirby KA. Nocturnal leg cramps. Am Fam Physician 2012;86(4):350-5. PMID 22963024
03: American Academy of Sleep Medicine. International classification of sleep disorders. 3rd edition TR. Darien, IL: American Academy of Sleep Medicine, 2023.**
04: Andrews AW, Pine R. Physical therapy for nocturnal lower limb cramp: a case report. Physiother Theory Pract 2019:35(2):190-7. PMID 29482418
05: Baldissera F, Cavallari P, Dworzak F. Motor neuron ‘bistability’: a pathogenetic mechanism for cramps and myokymia. Brain 1994;117:929-39. PMID 7953602
06: Barna O, Lohoida P, Holovchenko Y, et al. A randomized, double-blind, placebo-controlled, multicenter study assessing the efficacy of magnesium oxide monohydrate in the treatment of nocturnal leg cramps. Nutr J 2021;20(1):90. PMID 34719399
07: Barone P, Amboni M, Vitale C, Bonavita V. Treatment of nocturnal disturbances and excessive daytime sleepiness in Parkinson's disease. Neurology 2004;63(8 Suppl 3):S35-8. PMID 15505142
08: Bertolasi L, Priori A, Tomelleri G, et al. Botulinum toxin treatment of muscle cramps: a clinical and neurophysiological study. Ann Neurol 1997;41:181-6. PMID 9029067
09: Blyton F, Chuter V, Walter KE, Burns J. Non-drug therapies for lower limb muscle cramps. Cochrane Database Syst Rev 2012;1:CD008496. PMID 22258986
10: Borgen LA, Okerholm RA, Lai A, Scharf MB. The pharmacokinetics of sodium oxybate oral solution following acute and chronic administration to narcoleptic patients. J Clin Pharmacol 2004;44(3):253-7. PMID 14973300
11: Brasic JR. Risks of the consumption of beverages containing quinine. Psychol Rep 2003;93(3 Pt 2):1022-4. PMID 14765563
12: Butler JV, Mulkerrin EC, O'Keeffe ST. Nocturnal leg cramps in older people. Postgrad Med J 2002;78:596-8. PMID 12415081
13: Cecchin CR, Felix TM, Magalhaes RB, Furlanetto TW. Satoyoshi syndrome in a Caucasian girl improved with glucocorticoids--a clinical report. Am J Med Genet 2003;118A(1):52-4. PMID 12605441
14: Chiba S, Saitoh M, Hatanaka Y, et al. Autosomal dominant muscle cramp syndrome in a Japanese family. J Neurol Neurosurg Psychiatry 1999;67:116-9. PMID 10369837
15: Connolly PS, Shirley EA, Wasson JH, Nierenberg DW. Treatment of nocturnal leg cramps: a crossover trial of quinine vs vitamin E. Arch Intern Med 1992;152:1877-80. PMID 1520054
16: Coppin RJ, Wicke DM, Little PS. Managing nocturnal leg cramps--calf-stretching exercises and cessation of quinine treatment: a factorial randomised controlled trial. Br J Gen Pract 2005;55(512):186-91. PMID 15808033
17: D'Abreu A, Franca M JR, Conz L, et al. Sleep symptoms and their clinical correlates in Machado-Joseph disease. Acta Neurol Scand 2009;119(4):277-80. PMID 18771522
18: Delacour C, Chambe J, Lefebvre F, et al. Association between physical activity and nocturnal leg cramps in patients over 60 years old: a case-control study. Sci Rep 2020;10(1):2638. PMID 32060316
19: Diener HC, Baurecht W. Tolerability, compliance, quality of life, and clinical outcome during treatment with quinine sulfate in patients with nocturnal calf cramps. A multicenter non-interventional study (NIS) in adults. MMW Fortschr Med 2019;161(Suppl 6):24-31. PMID 31587167
20: Diener HC, Dethlefsen U, Dethlefsen-Gruber S, Verbeek P. Effectiveness of quinine in treating muscle cramps: a double-blind, placebo-controlled, parallel-group, multicentre trial. Int J Clin Pract 2002;56:243-6. PMID 12074203
21: Ferini-Strambi L. RLS-like symptoms: differential diagnosis by history and clinical assessment. Sleep Med 2007;8(Suppl 2):S3-6. PMID 17567532
22: Filosto M, Bertolasi L, Fincati E, et al. Axillary injection of botulinum A toxin in a patient with muscle cramps associated with severe axillary hyperhydrosis. Acta Neurol Belg 2001;101:121-3. PMID 11486559
23: Gamboni A, Perino A, Montrasio G. Gitelman syndrome in a 11 year old boy: incidental or delayed diagnosis. Pediatr Med Chir 2003;25(1):58-9. PMID 25419590
24: Garrison SR. Prophylactic stretching is unlikely to prevent nocturnal leg cramps. J Physiother 2014;60(3):174. PMID 25132650
25: Garrison SR, Allan GM, Sekhon RK, Musini VM, Khan KM. Magnesium for skeletal muscle cramps. Cochrane Database Syst Rev 2012b;9:CD009402. PMID 22972143
26: Garrison SR, Birmingham CL, Koehler BE, McCollom RA, Khan KM. The effect of magnesium infusion on rest cramps: randomized controlled trial. J Gerontol A Biol Med Sci 2011;66(6):661-6. PMID 21289017
27: Garrison SR, Dormuth CR, Morrow RL, Carney GA, Khan KM. Nocturnal leg cramps and prescription use that precedes them: a sequence symmetry analysis. Arch Intern Med 2012a;172(2):120-6. PMID 22157068
28: Grandner MA, Winkelman JW. Nocturnal leg cramps: prevalence and associations with demographics, sleep disturbance symptoms, medical conditions, and cardiometabolic risk factors. PLoS One 2017;12(6):e0178465. PMID 28586374
29: Guay DR. Are there alternatives to the use of quinine to treat nocturnal leg cramps. Consult Pharm 2008;23(2):141-56. PMID 18454580
30: Hallegraeff J, de Greef M. Pilot testing a stretching regimen for prevention of night time nocturnal leg cramps. Geriatr Nurs 2020;41(2):105-9. PMID 31405532
31: Hallegraeff JM, van der Schans CP, de Ruiter R, de Greef MH. Stretching before sleep reduces the frequency and severity of nocturnal leg cramps in older adults: a randomised trial. J Physiother 2012;58:17-22. PMID 22341378
32: Handa J, Otani K, Nikaido T, Kikuchi SI, Konno SI. Nocturnal leg cramps and lumbar spinal stenosis: a cross-sectional study in the community. Int J Gen Med 2022;15:7985-93. PMID 36345529
33: Haskell SG, Fiebach NH. Clinical epidemiology of nocturnal leg cramps in male veterans. Am J Med Sci 1997;313:210-4. PMID 9099150
34: Hawke F, Burns J. New evidence for stretching for preventing nocturnal cramps. Arch Intern Med 2012;172(22):1770-1. PMID 23229945
35: Hawke F, Chuter V, Burns J. Factors associated with night-time calf muscle cramps: a case-control study. Muscle Nerve 2013;47(3):339-43. PMID 23169577
36: Hawke F, Sadler SG, Katzberg HD, Pourkazemi F, Chuter V, Burns J. Non-drug therapies for the secondary prevention of lower limb muscle cramps. Cochrane Database Syst Rev 2021;5(5):CD008496. PMID 33998664
37: Hening WA, Allen RP, Washburn M, Lesage SR, Earley CJ. The four diagnostic criteria for Restless Legs Syndrome are unable to exclude confounding conditions ("mimics"). Sleep Med 2009;10(9):976-81. PMID 19185537
38: Hensley JG. Leg cramps and restless legs syndrome during pregnancy. J Midwifery Womens Health 2009;54(3):211-8. PMID 19410213
39: Hertz G, Fast A, Feinsilver SH, Albertano CL, Schulman H, Fein AM. Sleep in normal late pregnancy. Sleep 1992;15:246-51. PMID 1621025
40: Hinoshita F, Ogura Y, Suzuki Y, et al. Effect of orally administered shao-yao-gan-cao-tang (Shakuyaku-kanzo-to) on muscle cramps in maintenance hemodialysis patients: a preliminary study. Am J Chin Med 2003;31(3):445-53. PMID 12943175
41: Hogan DB. Quinine: not a safe drug for treating nocturnal leg cramps. CMAJ 2015;187(4):237-8. PMID 25623647
42: Imura T, Inoue G, Nakazawa T, et al. Treatment of nocturnal leg cramps by blockade of the medial branch of the deep peroneal nerve after lumbar spine surgery. Brain Behav 2015;5(9):e00370. PMID 26445706
43: Iwasa M, Karino Y, Kawaguchi T, et al. Relationship of muscle cramps to quality of life and sleep disturbance in patients with chronic liver diseases: a nationwide study. Liver Int 2018;38(12):2309-16. PMID 29582541
44: Jacobsen JH, Rosenberg RS, Huttenlocher PR, Spire JP. Familial nocturnal cramping. Sleep 1986;9:54-60. PMID 3961367
45: Jung WS, Moon SK, Park SU, Ko CN, Cho KH. Clinical assessment of usefulness, effectiveness and safety of jackyakamcho-tang (shaoyaogancao-tang) on muscle spasm and pain: a case series. Am J Chin Med 2004;32:611-20. PMID 15481650
46: Kanaan N, Sawaya R. Nocturnal leg cramps. Clinically mysterious and painful – but manageable. Geriatrics 2001;56:34-42. PMID 11417373
47: Kanai K, Kuwabara S, Arai K, Sung JY, Ogawara K, Hattori T. Muscle cramp in Machado-Joseph disease: altered motor axonal excitability properties and mexiletine treatment. Brain 2003;126(Pt 4):965-73. PMID 12615652
48: Khajehdehi P, Mojerleu M, Behzadi S, Rais-Jalali GA. A randomized, double blind, placebo-controlled trial of supplementary vitamins E, C and their combination for treatment of haemodialysis cramps. Nephrol Dial Transplant 2001;16:1448-51. PMID 11427639
49: Kim DH, Yoon DM, Yoon KB. The effects of myofascial trigger point injections on nocturnal calf cramps. J Am Board Fam Med 2015;28(1):21-7. PMID 25567819
50: Kim HJ, Yoon KB, Kang M, Lee HW, Kim SH. Use of baclofen as a treatment for nocturnal calf cramps in individuals with lumbar spinal stenosis: a prospective randomized study. Am J Phys Med Rehabil 2024;103(5):384-9. PMID 38063320
51: Koebnick C, Leitzmann R, Garcia AL, et al. Long-term effect of a plant-based diet on magnesium status during pregnancy. Eur J Clin Nutr 2005;59:219-25. PMID 15454974
52: Kothare SV, Khurana DS, Mostofi N, et al. Oxcarbazepine monotherapy in children and adolescents: a single-center clinical experience. Pediatr Neurol 2006;35:235-9. PMID 16996394
53: Kugelmas M. Preliminary observation: oral zinc sulfate replacement is effective in treating muscle cramps in cirrhotic patients. J Am Coll Nutr 2000;19:13-5. PMID 10682870
54: Kurschat C, Heering P, Grabensee B. Gitelman's syndrome: an important differential diagnosis of hypokalemia. Dtsch Med Wochenschr 2003;128(22):1225-8. PMID 12772080
55: Leroy F, Bridoux F, Abou-Ayache R, et al. Quinine-induced renal bilateral cortical necrosis. Nephrol Ther 2008;4(3):181-6. PMID 18343736
56: Leung AK, Wong BE, Chan PY, Cho HY. Nocturnal leg cramps in children: incidence and clinical characteristics. J Natl Med Assoc 1999;91:329-32. PMID 10388258
57: Maisonneuve H, Chambe J, Delacour C, et al. Prevalence of cramps in patients over the age of 60 in primary care: a cross sectional study. BMC Fam Pract 2016;17(1):111. PMID 27520635
58: Manila MN. Leg cramps in relation to metabolic syndrome. Georgian Med News 2009;166:51-4. PMID 19202219
59: Man-Son-Hing M, Wells G, Lau A. Quinine for nocturnal leg cramps: a meta-analysis including unpublished data. J Gen Intern Med 1998;13:600-6. PMID 9754515
60: Marini C, Lia A, Liguori R, et al. Familial cramping syndrome. Ital J Neurol Sci 1995;(suppl 7):64.
61: Matsumoto M, Watanabe K, Tsuji T, et al. Nocturnal leg cramps: a common complaint in patients with lumbar spinal canal stenosis. Spine 2009;34(5):E189-94. PMID 19247159
62: Miller TM, Layzer RB. Muscle cramps. Muscle Nerve 2005;32(4):431-42. PMID 15902691
63: Minetto MA, Botter A. Elicitability of muscle cramps in different leg and foot muscles. Muscle Nerve 2009;40(4):535-44. PMID 19623637
64: Minetto MA, Botter A, De Grandis D, Merletti R. Time and frequency domain analysis of surface myoelectric signals during electrically-elicited cramps. Neurophysiol Clin 2009;39(1):15-25. PMID 19268843
65: Moller C, Wetter TC, Köster J, Stiasny-Kolster K. Differential diagnosis of unpleasant sensations in the legs: prevalence of restless legs syndrome in a primary care population. Sleep Med 2010;11(2):161-6. PMID 20022805
66: Monderer RS, Wu WP, Thorpy MJ. Nocturnal leg cramps. Curr Neurol Neurosci Rep 2010;10(1):53-9. PMID 20425227
67: Ohayon MM, Zulley J, Guilleminault C, Smirne S. Prevalence and pathologic associations of sleep paralysis in the general population. Neurology 1999;52:1194-200. PMID 10214743
68: Pires ML, Benedito-Silva AA, Mello MT, Pompeia Sdel G, Tufik S. Sleep habits and complaints of adults in the city of Sao Paulo, Brazil, in 1987 and 1995. Braz J Med Biol Res 2007;40(11):1505-15. PMID 17934647
69: Poynard T, Valterio C. Meta-analysis of hydroxyethylrutosides in the treatment of chronic venous insufficiency. Vasa 1994;23:244-50. PMID 7975870
70: Prateepavanich P, Kupniratsaikul V, Charoensak T. The relationship between myofascial trigger points of gastrocnemius muscle and nocturnal calf cramps. J Med Assoc Thai 1999;82:451-9. PMID 10443094
71: Rabbitt L, Mulkerrin EC, O'Keeffe ST. A review of nocturnal leg cramps in older people. Age Ageing 2016;45(6):776-82. PMID 27515677
72: Rajabally YA, Delmont E, Hiew FL, et al. Prevalence, correlates and impact of pain and cramps in anti-MAG neuropathy: a multicenter European study. Eur J Neurol 2018;25(1):135-41. PMID 28906575
73: Ramachandran R, Wierzbicki AS. Statins, muscle disease, and mitochondria. J Clin Med 2017;6(8):75. PMID 28757597
74: Roeleveld K, Van Engelen BG, Stegeman DF. Possible mechanisms of muscle cramps from temporal and spatial surface EMG characteristics. J Appl Physiol 2000;88:1698-706. PMID 10797132
75: Roguin Maor N, Alperin M, Shturman E, et al. Effect of magnesium oxide supplementation on nocturnal leg cramps: a randomized clinical trial. JAMA Intern Med 2017;177(5): 617-23. PMID 28241153
76: Roman GC, Rogers SJ. Donepezil: a clinical review of current and emerging indications. Expert Opin Pharmacother 2004;5(1):161-80. PMID 14680445
77: Sako K, Imamura Y, Nishimata H, Tahara K, Kubozono O, Tsubouchi H. Branched-chain amino acids supplements in the late evening decrease the frequency of muscle cramps with advanced hepatic cirrhosis. Hepatol Res 2003;26(4):327-9. PMID 12963433
78: Schwellnus MP, Derman EW, Noakes TD. Aetiology of skeletal muscle “cramps” during exercise: a novel hypothesis. J Sports Sci 1997;15:277-85. PMID 9232553
79: Schwellnus MP, Nicol J, Laubscher R, Noakes TD. Serum electrolyte concentrations and hydration status are not associated with exercise associated muscle cramping (EAMC) in distance runners. Br J Sports Med 2004;38:488-92. PMID 15273192
80: Sebo P, Cerutti B, Haller DM. Effect of magnesium therapy on nocturnal leg cramps: a systematic review of randomized controlled trials with meta-analysis using simulations. Fam Pract 2014;31(1):7-19. PMID 24280947
81: Sebo P, Haller D, Cerutti B, Maisonneuve H. A prospective observational study of the main features of nocturnal leg cramps in primary care. Swiss Med Wkly 2019;149:w20048. PMID 30905059
82: Sebo P, Haller DM, Kaiser C, et al. Health-related quality of life associated with nocturnal leg cramps in primary care: a mixed methods study. Fam Pract 2022;39(1):85-91. PMID 34278417
83: Sebo P, Haller D, Maisonneuve H. Quality of sleep in patients with nocturnal leg cramps and validity of a single-item measure of cramp-related sleep disturbance: an observational study. Swiss Med Wkly 2020;150:w20217. PMID 32329805
84: Serrao M, Rossi P, Cardinali P, Valente G, Parisi L, Pierelli F. Gabapentin treatment for muscle cramps: an open-label trial. Clin Neuropharmacol 2000;23:45-9. PMID 10682230
85: Sidorov J. Quinine sulfate for leg cramps: does it work. J Am Geriatr Soc 1993;41:498-500. PMID 8486881
86: Sohrabvand F, Shariat M, Haghollahi F. Vitamin B supplementation for leg cramps during pregnancy. Int J Gynaecol Obstet 2006;95(1):48-9. PMID 16919630
87: Sontag SJ, Wanner JN. The cause of leg cramps and knee pains: an hypothesis and effective treatment. Med Hypotheses 1988;25(1):35-41. PMID 3343944
88: Thompson PD, Clarkson P, Karas RH. Statin-associated myopathy. JAMA 2003;289(13):1681-90. PMID 12672737
89: Townend BS, Sturm JW, Whyte S. Quinine associated blindness. Aust Fam Physician 2004;33:627-8. PMID 15373380
90: Tunc T, Karadag YS, Dogulu F, Inan LE. Predisposing factors of restless legs syndrome in pregnancy. Mov Disord 2007;22(5):627-31. PMID 17285614
91: Vinciguerra G, Belcaro G, Cesarone MR, et al. Cramps and muscular pain: prevention with pycnogenol in normal subjects, venous patients, athletes, claudicants and in diabetic microangiopathy. Angiology 2006;57:331-9. PMID 16703193
92: Woodfield R, Goodyear-Smith F, Arroll B. N-of-1 trials of quinine efficacy in skeletal muscle cramps of the leg. Br J Gen Pract 2005;55(512):181-5. PMID 15808032
93: Xu D, Yang A, Ren R, Shan Z, Li YM, Tan J. Vitamin K2 as a potential therapeutic candidate for the prevention of muscle cramps in hemodialysis patients: a prospective multicenter, randomized, controlled, crossover pilot trial. Nutrition 2022;97:111608. PMID 35203045
94: Young G. Leg cramps. BMJ Clin Evid 2009;2009. PMID 19445755
95: Young GL, Jewell D. Interventions for leg cramps in pregnancy (Cochrane Review). Cochrane Database Syst Rev 2002;(1):CD000121. PMID 11869565

Contributors

All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Author

Jiri Nepozitek MD PhD

Dr. Nepozitek of Charles University and General University Hospital in Prague has no relevant financial relationships to disclose.
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Editor

Federica Provini MD

Dr. Provini of the University of Bologna and IRCCS Institute of Neurological Sciences of Bologna received speakers' fees from Idorsia, Italfarmaco, and NeoPharmed Gentili Spa.
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Former Authors

Michael J Thorpy MD
Pasquale Montagna MD
Stefano Zanigni MD
Harini Sarva MD

Patient Profile

Age range of presentation: 6 to 65+ years
Sex preponderance: male=female
Heredity: heredity may be a factor

autosomal dominant
Population groups selectively affected: none selectively affected
Occupation groups selectively affected: none selectively affected

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Sleep-related leg cramps

Associated Disorders

Abnormal calcium metabolism
Arthritis
Diabetes mellitus
Electrolyte disturbances
Hemodialysis
- Hypocalcemia
- Hypomagnesemia
- Hyponatremia
- Hypoparathyroidism
- Hypothyroidism
- Liver cirrhosis
- McArdle disease
- Myokymia
- Myopathy
- Myotonia
- Parkinson disease
- Periodic limb movement disorder
- Peripheral neuropathy
- Peripheral vascular disease
- Renal failure
- Restless leg syndrome
- Sleep-related bruxism
- Sleep-related movement disorder
- Sleep-related rhythmic movement disorder

Differential Diagnosis

other motor disturbances that may occur during sleep
periodic limb movements in sleep
restless legs syndrome
sleep starts
sudden bodily jerks during sleep
- painful legs and moving toes
- syndrome of excessive fragmentary myoclonus during sleep
- myokymia-cramp-fasciculation syndrome

Also Relevant

Hypothyroidism
Pregnancy: neuromuscular complications
Parasomnias
Parkinson disease
Periodic limb movements
- Restless legs syndrome
- Sleep bruxism
- Sleep disorders
- Sleep and mental disorders
- Sleep paralysis
- Sleep-related rhythmic movement disorder
- Sleeptalking

Sleep-related leg cramps …

Sleep-related leg cramps

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Confusing conditions

Diagnostic workup

Management

Special considerations

Pregnancy

References

Contributors

Author

Editor

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview.
Start a Free Account
to access the full version.

Questions or Comment?

Also in This Category

Hypersomnolence

Hemifacial spasm

Wilson disease

Fatal familial insomnia

Sleep and mental disorders

Sleep paralysis

Sleep and epilepsy

Narcolepsy

Sleep-related leg cramps

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Confusing conditions

Diagnostic workup

Management

Special considerations

Pregnancy

References

Contributors

Author

Editor

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Hypersomnolence

Hemifacial spasm

Wilson disease

Fatal familial insomnia

Sleep and mental disorders

Sleep paralysis

Sleep and epilepsy

Narcolepsy

This is an article preview.
Start a Free Account
to access the full version.