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Journal of Neurology

, Volume 262, Issue 8, pp 1814–1821 | Cite as

Neurogenic muscle cramps

  • Hans D. KatzbergEmail author
Review

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.

Keywords

Muscle crampscharlie horse Chopper Motor nerve hyperexcitability Spasms 

Notes

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.

References

  1. 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):1639–1643CrossRefPubMedGoogle Scholar
  2. 2.
    Abdulla AJ, Jones PW, Pearce VR (1999) Leg cramps in the elderly: prevalence, drug and disease associations. Int J Clin Pract 53:494–496PubMedGoogle Scholar
  3. 3.
    Naylor JR, Young JB (1994) A general population survey of rest cramps. Age Ageing 23:418–420CrossRefPubMedGoogle Scholar
  4. 4.
    Butler JV, Mulkerrin EC, O’Keeffe ST (2002) Nocturnal leg cramps in older people. Postgrad Med J 78:596–598PubMedCentralCrossRefPubMedGoogle Scholar
  5. 5.
    Lo Coco D, La Bella V (2012) Fatigue, sleep, and nocturnal complaints in patients with amyotrophic lateral sclerosis. Eur J Neurol 19(5):760–763CrossRefPubMedGoogle Scholar
  6. 6.
    Ganzini L, Johnston W, Hoffman W (1999) Correlates of suffering in amyotrophic lateral sclerosis. Neurology 52(7):1434–1440CrossRefPubMedGoogle Scholar
  7. 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):671–676CrossRefPubMedGoogle Scholar
  8. 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 PubMedCentralGoogle Scholar
  9. 9.
    Leung AK, Wong BE, Chan PY, Cho HY (1999) Nocturnal leg cramps in children: incidence and clinical characteristics. JAMA 91(6):329–332Google Scholar
  10. 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):89–94CrossRefPubMedGoogle Scholar
  11. 11.
    Kanaan N, Sawaya R (2001) Nocturnal leg cramps. Clinically mysterious and painful-but manageable. Geriatrics 56(6):39–42Google Scholar
  12. 12.
    Gulich M, Heil P, Zeitler H-P (1998) Epidemiology and determinants of nocturnal calf cramps. Eur J Gen Pract 4(3):109–113CrossRefGoogle Scholar
  13. 13.
    Katzberg H, Kokokyi S, Halpern E et al (2014) Prevalence of muscle cramps in patients with diabetes. Diabetes Care 37(1):17–18CrossRefGoogle Scholar
  14. 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 18:619–625CrossRefPubMedGoogle Scholar
  15. 15.
    Weiner IH, Weiner HL (1990) Nocturnal leg muscle cramps. JAMA 150:511–518Google Scholar
  16. 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):189–194CrossRefGoogle Scholar
  17. 17.
    Matzner O, Devor M (1994) Hyperexcitability at sites of nerve injury depends on voltage-sensitive Na+ channels. J Neurophysiol 72:349–359PubMedGoogle Scholar
  18. 18.
    Mense S (1996) Group III and IV receptors in skeletal muscle: are they specific or polymodal? Prog Brain Res 110:125–135CrossRefPubMedGoogle Scholar
  19. 19.
    Baldissera F, Cavallari P, Dworzak F (1994) Motor neuron ‘bistability’. A pathogenetic mechanism for cramps and myokymia. Brain 117(5):929–939CrossRefPubMedGoogle Scholar
  20. 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 102:1890–1901CrossRefPubMedGoogle Scholar
  21. 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 187:623–629CrossRefPubMedGoogle Scholar
  22. 22.
    Lindsay RM, Shulman T, Prakash S et al (2003) Hemodynamic and volume changes during hemodialysis. Hemodial Int 7:204–208CrossRefPubMedGoogle Scholar
  23. 23.
    Bertolasi L, De Grandis D, Bongiovanni LG, Zanette GP, Gasperini M (1993) The influence of muscular lengthening on cramps. Ann Neurol 33(2):176–180CrossRefPubMedGoogle Scholar
  24. 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):1228–1231CrossRefPubMedGoogle Scholar
  25. 25.
    Lopate G, Streif E, Harms M, Weihl C, Pestronk A (2013) Cramps and small-fiber neuropathy. Muscle Nerve 48:252–255CrossRefPubMedGoogle Scholar
  26. 26.
    Graven-Nielsen T, Mense S (2001) The peripheral apparatus of muscle pain: evidence from animal and human studies. Clin J Pain 17:2–10CrossRefPubMedGoogle Scholar
  27. 27.
    Jentsch TJ, Stein V, Weinreich F et al (2002) Molecular structure and physiological function of chloride channels. Physiol Rev 82:503–568CrossRefPubMedGoogle Scholar
  28. 28.
    Conte Camerino D, Tricarico D, Pierno S et al (2004) Taurine and skeletal muscle disorders. Neurochem Res 29:135–142CrossRefPubMedGoogle Scholar
  29. 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. 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):331–339CrossRefPubMedGoogle Scholar
  31. 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, PhiladelphiaGoogle Scholar
  32. 32.
    Samaha FJ, Quinlan JQ (1996) Dystrophinopathy with wide-ranging laboratory findings. J Child Neurol 11:21–24CrossRefPubMedGoogle Scholar
  33. 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):123–128PubMedGoogle Scholar
  34. 34.
    Schwellnus MP (2007) Muscle cramping in the marathon: aetiology and risk factors. Sports Med 37:364–367CrossRefPubMedGoogle Scholar
  35. 35.
    Schwellnus MP (2009) Cause of exercise associated muscle cramps (EAMC)—altered neuromuscular control, dehydration or electrolyte depletion? Br J Sports Med 43(6):401–408CrossRefPubMedGoogle Scholar
  36. 36.
    Hensley JG (2009) Leg cramps and restless legs syndrome during pregnancy. J Midwifery Womens Health 54(3):211–218CrossRefPubMedGoogle Scholar
  37. 37.
    Ng K, Lin CS, Murray NM et al (2007) Conduction and excitability properties of peripheral nerves in end-stage liver disease. Muscle Nerve 35:730–738CrossRefPubMedGoogle Scholar
  38. 38.
    Arieff AI (1994) Dialysis disequilibrium syndrome: current concepts on pathogenesis and prevention. Kidney Int 45:629–635CrossRefPubMedGoogle Scholar
  39. 39.
    Turken SA, Cafferty M, Silverberg SJ et al (1989) Neuromuscular involvement in mild, asymptomatic primary hyperparathyroidism. Am J Med 87:553–557CrossRefPubMedGoogle Scholar
  40. 40.
    Baera AN, Wortmannb RL (2007) Myotoxicity associated with lipid-lowering drugs. Curr Opin Rheumatol 19:67–73Google Scholar
  41. 41.
    Mosenkis A, Townsend RR (2005) Muscle cramps and diuretic therapy. J Clin Hyertens 7:134–135CrossRefGoogle Scholar
  42. 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 172:120–126CrossRefPubMedGoogle Scholar
  43. 43.
    Tahmoush AJ, Alonso RJ, Tahmoush GP, Heiman-Patterson TD (1991) Cramp-fasciculation syndrome: a treatable, hyperexcitable peripheral nerve disorder. Neurology 41:1021–1024CrossRefPubMedGoogle Scholar
  44. 44.
    Shillito P, Molenaar PC, Vincent A et al (1995) Acquired neuromyotonia: evidence for autoantibodies directed against K+ channels of peripheral nerves. Ann Neurol 38:714–722CrossRefPubMedGoogle Scholar
  45. 45.
    Liewluck T, Klein CJ, Jones LK Jr (2013) Fasciculation syndrome in patients with and without neural autoantibodies. Muscle Nerve 49(3):351–356CrossRefPubMedGoogle Scholar
  46. 46.
    Jacobsen JH, Rosenberg RS, Huttenlocher PR, Spire JP (1986) Familial nocturnal cramping. Sleep 9:54–60PubMedGoogle Scholar
  47. 47.
    Harrison TB, Benatar M (2007) Accuracy of repetitive nerve stimulation for diagnosis of the cramp-fasciculation syndrome. Muscle Nerve 35:776–780CrossRefPubMedGoogle Scholar
  48. 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 38:1151–1154PubMedGoogle Scholar
  49. 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 173:175–180CrossRefPubMedGoogle Scholar
  50. 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 8:326–330Google Scholar
  51. 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 48:868–871PubMedGoogle Scholar
  52. 52.
    Kawaguchi T, Izumi N, Charlton MR et al (2011) Branched-chain amino acids as pharmacological nutrients in chronic liver disease. Hepatology 54:1063–1070CrossRefPubMedGoogle Scholar
  53. 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):445–451CrossRefPubMedGoogle Scholar
  54. 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 152:1877–1880CrossRefPubMedGoogle Scholar
  55. 55.
    Jansen PH, Veenhuizen KC, Wesseling AI, de Boo T, Verbeek AL (1997) Randomised controlled trial of hydroquinine in muscle cramps. Lancet 349:528–532CrossRefPubMedGoogle Scholar
  56. 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 56:243–246PubMedGoogle Scholar
  57. 57.
    Bateman DN, Dyson EH (1986) Quinine toxicity. Adv Drug React 4:215–233Google Scholar
  58. 58.
    Food and Drug Administration, Department of Health and Human Services (2006) Drug products containing quinine; enforcement action dates. Fed Reg 71:75557–75560Google Scholar
  59. 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):691–696CrossRefPubMedGoogle Scholar
  60. 60.
    Voon WC, Sheu SH (2001) Diltiazem for nocturnal leg cramps. Age Ageing 30:91–92CrossRefPubMedGoogle Scholar
  61. 61.
    Fat MJ, Kokokyi S, Katzberg HD (2013) Neurologist practice patterns in treatment of muscle cramps in Canada. J Foot Ankle Res 6:2PubMedCentralCrossRefPubMedGoogle Scholar
  62. 62.
    Miller RG, Moore DH, Gelinas DF et al (2001) Phase III randomized trial of gabapentin in patients with amyotrophic lateral sclerosis. Neurology 56:843–848CrossRefPubMedGoogle Scholar
  63. 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 26:1–6Google Scholar
  64. 64.
    Verdru P, Leenders J, Van Hees J (1992) Cramp-fasciculation syndrome. Neurology 42(9):1846–1847CrossRefGoogle Scholar
  65. 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):1135–1140CrossRefPubMedGoogle Scholar
  66. 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):284–289CrossRefPubMedGoogle Scholar
  67. 67.
    Young JB, Connolly MJ (1993) Naftidrofuryl treatment for rest cramp. Postgrad Med J 69:624–626PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.University of TorontoTorontoCanada
  2. 2.University Health NetworkTorontoCanada
  3. 3.Toronto General Hospital/UHNTorontoCanada

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