Skip to main content

Advertisement

Log in

An Erratum to this article was published on 06 January 2016

Abstract

Muscle cramps are sustained, painful contractions of muscle and are prevalent in patients with and without medical conditions. The objective of this review is to present updates on the mechanism, investigation and treatment of neurogenic muscle cramps. PubMed and Embase databases were queried between January 1980 and July 2014 for English-language human studies. The American Academy of Neurology classification of studies (classes I–IV) was used to assess levels of evidence. Mechanical disruption, ephaptic transmission, disruption of sensory afferents and persistent inward currents have been implicated in the pathogenesis of neurogenic cramps. Investigations are directed toward identifying physiological triggers or medical conditions predisposing to cramps. Although cramps can be self-limiting, disabling or sustained muscle cramps should prompt investigation for underlying medical conditions. Lifestyle modifications, treatment of underlying conditions, stretching, B-complex vitamins, diltiezam, mexiletine, carbamazepine, tetrahydrocannabinoid, leveteracitam and quinine sulfate have shown evidence for treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

References

  1. Gronseth G, French J (2008) Practice parameters and technology assessments: what they are, what they are not, and why you should care. Neurology 71(20):1639–1643

    Article  PubMed  Google Scholar 

  2. Abdulla AJ, Jones PW, Pearce VR (1999) Leg cramps in the elderly: prevalence, drug and disease associations. Int J Clin Pract 53:494–496

    CAS  PubMed  Google Scholar 

  3. Naylor JR, Young JB (1994) A general population survey of rest cramps. Age Ageing 23:418–420

    Article  CAS  PubMed  Google Scholar 

  4. Butler JV, Mulkerrin EC, O’Keeffe ST (2002) Nocturnal leg cramps in older people. Postgrad Med J 78:596–598

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Lo Coco D, La Bella V (2012) Fatigue, sleep, and nocturnal complaints in patients with amyotrophic lateral sclerosis. Eur J Neurol 19(5):760–763

    Article  CAS  PubMed  Google Scholar 

  6. Ganzini L, Johnston W, Hoffman W (1999) Correlates of suffering in amyotrophic lateral sclerosis. Neurology 52(7):1434–1440

    Article  CAS  PubMed  Google Scholar 

  7. Maxwell SK, Kokokyi S, Breiner A, Ebadi H, Bril V, Katzberg HD (2014) Characteristics of muscle cramps in patients with polyneuropathy. Neuromuscul Disord 24(8):671–676

    Article  PubMed  Google Scholar 

  8. Johnson NE, Sowden J, Dilek N et al (2014) Prospective Study of Muscle Cramps in Charcot-Marie-Tooth Disease. Muscle Nerve. doi:10.1002/mus.24333

    PubMed Central  Google Scholar 

  9. Leung AK, Wong BE, Chan PY, Cho HY (1999) Nocturnal leg cramps in children: incidence and clinical characteristics. JAMA 91(6):329–332

    CAS  Google Scholar 

  10. Jansen PH, Gabreëls FJ, van Engelen BG (2002) Diagnosis and differential diagnosis of muscle cramps: a clinical approach. J Clin Neuromuscul Dis 4(2):89–94

    Article  PubMed  Google Scholar 

  11. Kanaan N, Sawaya R (2001) Nocturnal leg cramps. Clinically mysterious and painful-but manageable. Geriatrics 56(6):39–42

    Google Scholar 

  12. Gulich M, Heil P, Zeitler H-P (1998) Epidemiology and determinants of nocturnal calf cramps. Eur J Gen Pract 4(3):109–113

    Article  Google Scholar 

  13. Katzberg H, Kokokyi S, Halpern E et al (2014) Prevalence of muscle cramps in patients with diabetes. Diabetes Care 37(1):17–18

    Article  Google Scholar 

  14. Redmond AC, Burns J, Ouvrier RA (2008) Factors that influence health-related quality of life in Australia adults with Charcot-Marie-Tooth disease. Neuromuscul Disord 18:619–625

    Article  PubMed  Google Scholar 

  15. Weiner IH, Weiner HL (1990) Nocturnal leg muscle cramps. JAMA 150:511–518

    Google Scholar 

  16. Matsumoto M, Watanabe K, Tsuji T et al (2009) Nocturnal leg cramps: a common complaint in patients with lumbar spinal canal stenosis. Spine 34(5):189–194

    Article  Google Scholar 

  17. Matzner O, Devor M (1994) Hyperexcitability at sites of nerve injury depends on voltage-sensitive Na+ channels. J Neurophysiol 72:349–359

    CAS  PubMed  Google Scholar 

  18. Mense S (1996) Group III and IV receptors in skeletal muscle: are they specific or polymodal? Prog Brain Res 110:125–135

    Article  CAS  PubMed  Google Scholar 

  19. Baldissera F, Cavallari P, Dworzak F (1994) Motor neuron ‘bistability’. A pathogenetic mechanism for cramps and myokymia. Brain 117(5):929–939

    Article  PubMed  Google Scholar 

  20. Minetto MA, Holobar A, Botter A, Farina D (2009) Discharge properties of motor units of the abductor hallucis muscle during cramp contractions. J Neurophysiol 102:1890–1901

    Article  PubMed  Google Scholar 

  21. Ge HY, Zhang Y, Boudreau S, Yue SW, Arendt-Nielsen L (2008) Induction of muscle cramps by nociceptive stimulation of latency myofascial trigger points. Exp Brain Res 187:623–629

    Article  PubMed  Google Scholar 

  22. Lindsay RM, Shulman T, Prakash S et al (2003) Hemodynamic and volume changes during hemodialysis. Hemodial Int 7:204–208

    Article  PubMed  Google Scholar 

  23. Bertolasi L, De Grandis D, Bongiovanni LG, Zanette GP, Gasperini M (1993) The influence of muscular lengthening on cramps. Ann Neurol 33(2):176–180

    Article  CAS  PubMed  Google Scholar 

  24. Obi T, Mizoguchi K, Matsuoka H, Takatsu M, Nishimura Y (1993) Muscle cramp as the result of impaired GABA function—an electrophysiological and pharmacological observation. Muscle Nerve 16(11):1228–1231

    Article  CAS  PubMed  Google Scholar 

  25. Lopate G, Streif E, Harms M, Weihl C, Pestronk A (2013) Cramps and small-fiber neuropathy. Muscle Nerve 48:252–255

    Article  CAS  PubMed  Google Scholar 

  26. Graven-Nielsen T, Mense S (2001) The peripheral apparatus of muscle pain: evidence from animal and human studies. Clin J Pain 17:2–10

    Article  CAS  PubMed  Google Scholar 

  27. Jentsch TJ, Stein V, Weinreich F et al (2002) Molecular structure and physiological function of chloride channels. Physiol Rev 82:503–568

    Article  CAS  PubMed  Google Scholar 

  28. Conte Camerino D, Tricarico D, Pierno S et al (2004) Taurine and skeletal muscle disorders. Neurochem Res 29:135–142

    Article  PubMed  Google Scholar 

  29. Baizabal-Carvallo JF, Jankovic J (2014) Stiff-person syndrome: insights into a complex autoimmune disorder. J Neurol Neurosurg Psychiatry. doi:10.1136/jnnp-2014-309201

    Google Scholar 

  30. Vinciguerra G, Belcaro G et al (2006) Cramps and muscular pain: prevention with pycnogenol in normal subjects, venous patients, athletes, claudicants and in diabetic microangiopathy. Angiology 57(3):331–339

    Article  CAS  PubMed  Google Scholar 

  31. Kishnani PS, Chen YT (2011) Type V glycogen storage disease. In: Kliegman RM, Stanton BF, St. Geme J, Schor N, Behrman RE (eds) Nelson Textbook of Pediatrics, vol chapt 81, 19th edn. Elsevier, Philadelphia

    Google Scholar 

  32. Samaha FJ, Quinlan JQ (1996) Dystrophinopathy with wide-ranging laboratory findings. J Child Neurol 11:21–24

    Article  CAS  PubMed  Google Scholar 

  33. Drobny M, Pullmann R, Odalos I, Skerenova M, Saniova B (2014) Incidence of skeletal muscle disorders after statins’ treatment: consequences in clinical and EMG picture. Neuro Endocrinol Lett 35(2):123–128

    CAS  PubMed  Google Scholar 

  34. Schwellnus MP (2007) Muscle cramping in the marathon: aetiology and risk factors. Sports Med 37:364–367

    Article  PubMed  Google Scholar 

  35. Schwellnus MP (2009) Cause of exercise associated muscle cramps (EAMC)—altered neuromuscular control, dehydration or electrolyte depletion? Br J Sports Med 43(6):401–408

    Article  CAS  PubMed  Google Scholar 

  36. Hensley JG (2009) Leg cramps and restless legs syndrome during pregnancy. J Midwifery Womens Health 54(3):211–218

    Article  PubMed  Google Scholar 

  37. Ng K, Lin CS, Murray NM et al (2007) Conduction and excitability properties of peripheral nerves in end-stage liver disease. Muscle Nerve 35:730–738

    Article  PubMed  Google Scholar 

  38. Arieff AI (1994) Dialysis disequilibrium syndrome: current concepts on pathogenesis and prevention. Kidney Int 45:629–635

    Article  CAS  PubMed  Google Scholar 

  39. Turken SA, Cafferty M, Silverberg SJ et al (1989) Neuromuscular involvement in mild, asymptomatic primary hyperparathyroidism. Am J Med 87:553–557

    Article  CAS  PubMed  Google Scholar 

  40. Baera AN, Wortmannb RL (2007) Myotoxicity associated with lipid-lowering drugs. Curr Opin Rheumatol 19:67–73

    Google Scholar 

  41. Mosenkis A, Townsend RR (2005) Muscle cramps and diuretic therapy. J Clin Hyertens 7:134–135

    Article  Google Scholar 

  42. Garrison SR, Dormuth CR, Morrow RL, Carney GA, Khan HM (2012) Nocturnal leg cramps and prescription use that precedes them: a sequence symmetry analysis. Arch Intern Med 172:120–126

    Article  PubMed  Google Scholar 

  43. Tahmoush AJ, Alonso RJ, Tahmoush GP, Heiman-Patterson TD (1991) Cramp-fasciculation syndrome: a treatable, hyperexcitable peripheral nerve disorder. Neurology 41:1021–1024

    Article  CAS  PubMed  Google Scholar 

  44. Shillito P, Molenaar PC, Vincent A et al (1995) Acquired neuromyotonia: evidence for autoantibodies directed against K+ channels of peripheral nerves. Ann Neurol 38:714–722

    Article  CAS  PubMed  Google Scholar 

  45. Liewluck T, Klein CJ, Jones LK Jr (2013) Fasciculation syndrome in patients with and without neural autoantibodies. Muscle Nerve 49(3):351–356

    Article  PubMed  Google Scholar 

  46. Jacobsen JH, Rosenberg RS, Huttenlocher PR, Spire JP (1986) Familial nocturnal cramping. Sleep 9:54–60

    CAS  PubMed  Google Scholar 

  47. Harrison TB, Benatar M (2007) Accuracy of repetitive nerve stimulation for diagnosis of the cramp-fasciculation syndrome. Muscle Nerve 35:776–780

    Article  PubMed  Google Scholar 

  48. Chan P, Huang TY, Chen YJ, Huang WP, Liu YC (1998) Randomized, double-blind, placebo-controlled study of the safety and efficacy of vitamin B complex in the treatment of nocturnal leg cramps in elderly patients with hypertension. J Clin Pharmacol 38:1151–1154

    CAS  PubMed  Google Scholar 

  49. Dahle LO, Berg G, Hammar M, Hurtig M, Larsson L (1995) The effect of oral magnesium substitution on pregnancy induced leg cramps. Am J Obstet Gynecol 173:175–180

    Article  CAS  PubMed  Google Scholar 

  50. Roffe C, Sills S, Crome P, Jones P (2002) Randomised, cross-over, placebo controlled trial of magnesium citrate in the treatment of chronic persistent leg cramps. Med Sci Monit 8:326–330

    Google Scholar 

  51. Frusso R, Zarate M, Augustovski F, Rubinstein A (1999) Magnesium for the treatment of nocturnal leg cramps: a crossover randomized trial. J Fam Pract 48:868–871

    CAS  PubMed  Google Scholar 

  52. Kawaguchi T, Izumi N, Charlton MR et al (2011) Branched-chain amino acids as pharmacological nutrients in chronic liver disease. Hepatology 54:1063–1070

    Article  CAS  PubMed  Google Scholar 

  53. Sidhom OA, Odeh YK, Krumlovsky FA, Budris WA, Wang Z, Pospisil PA, Atkinson AJ (1994) Low-dose prazosin in patients with muscle cramps during hemodialysis. Clin Pharmacol Ther 56(4):445–451

    Article  CAS  PubMed  Google Scholar 

  54. Connolly PS, Shirley EA, Wasson JH, Nierenberg DW (1992) Treatment of nocturnal leg cramps: a crossover trial of quinine vs vitamin E. Arch Intern Med 152:1877–1880

    Article  CAS  PubMed  Google Scholar 

  55. Jansen PH, Veenhuizen KC, Wesseling AI, de Boo T, Verbeek AL (1997) Randomised controlled trial of hydroquinine in muscle cramps. Lancet 349:528–532

    Article  CAS  PubMed  Google Scholar 

  56. Diener HC, Dethlefsen U, Dethlefsen-Gruber S, Verbeek P (2002) Efficacy of quinine in treating muscle cramps: a double-blind, placebo-controlled, parallel-group, multicentre trial. Int J Clin Pract 56:243–246

    CAS  PubMed  Google Scholar 

  57. Bateman DN, Dyson EH (1986) Quinine toxicity. Adv Drug React 4:215–233

    Google Scholar 

  58. Food and Drug Administration, Department of Health and Human Services (2006) Drug products containing quinine; enforcement action dates. Fed Reg 71:75557–75560

    Google Scholar 

  59. Katzberg HD, Khan AH, So YT (2010) Assessment: symptomatic treatment for muscle cramps (an evidence-based review): Report of the therapeutics and technology assessment subcommittee of the american academy of neurology. Neurology 74(8):691–696

    Article  CAS  PubMed  Google Scholar 

  60. Voon WC, Sheu SH (2001) Diltiazem for nocturnal leg cramps. Age Ageing 30:91–92

    Article  CAS  PubMed  Google Scholar 

  61. Fat MJ, Kokokyi S, Katzberg HD (2013) Neurologist practice patterns in treatment of muscle cramps in Canada. J Foot Ankle Res 6:2

    Article  PubMed Central  PubMed  Google Scholar 

  62. Miller RG, Moore DH, Gelinas DF et al (2001) Phase III randomized trial of gabapentin in patients with amyotrophic lateral sclerosis. Neurology 56:843–848

    Article  CAS  PubMed  Google Scholar 

  63. Bedlack RS, Pastula DM, Hawes J, Heydt D (2008) Open-label pilot trial of levetiracetam for cramps and spasticity in patients with motor neuron disease. Amyotroph Lateral Scler 26:1–6

    Google Scholar 

  64. Verdru P, Leenders J, Van Hees J (1992) Cramp-fasciculation syndrome. Neurology 42(9):1846–1847

    Article  Google Scholar 

  65. Weber M, Goldman B, Truniger S (2010) Tetrahydrocannabinol (THC) for cramps in amyotrophic lateral sclerosis: a randomised, double-blind crossover trial. J Neurol Neurosurg Psychiatry 81(10):1135–1140

    Article  CAS  PubMed  Google Scholar 

  66. Kuwabara S, Misawa S, Tamura N et al (2005) The effects of mexiletine on excitability properties of human median motor axons. Clin Neurophysiol 116(2):284–289

    Article  CAS  PubMed  Google Scholar 

  67. Young JB, Connolly MJ (1993) Naftidrofuryl treatment for rest cramp. Postgrad Med J 69:624–626

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The author would like to acknowledge the assistance of Ms. Kimberly Chin in the generation of Fig. 1, Pathophysiology of Neurogenic Muscle Cramps.

Conflicts of interest

Dr. Katzberg drafted the manuscript and performed literature review. He has received travel support from Genzyme Corporation and grants from CSL Behring and Grifols, Canada, Ltd. There are no direct conflicts of interest in the preparation of this manuscript.

Ethical standard

This study does not contain clinical data or patient information.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hans D. Katzberg.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Katzberg, H.D. Neurogenic muscle cramps. J Neurol 262, 1814–1821 (2015). https://doi.org/10.1007/s00415-015-7659-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-015-7659-x

Keywords

Navigation