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Myoclonus: Pathophysiology and Treatment Options

  • Ariel Levy
  • Robert Chen
Movement Disorders (A Videnovich, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Movement Disorders

Opinion statement

Treatment of myoclonus requires an understanding of the physiopathology of the condition. The first step in treatment is to determine if there is an epileptic component to the myoclonus and treat accordingly. Secondly, a review of medications (e.g., opiates) and comorbidities (e.g., hepatic or renal failure) is required to establish the possibility of iatrogenic and reversible conditions. Once those are eliminated, delineation between cortical, cortico-subcortical, subcortical, brainstem, and spinal generators can determine the first-line treatment. Cortical myoclonus can be treated with levetiracetam, valproic acid, and clonazepam as first-line agents. Phenytoin and carbamazepine may paradoxically worsen myoclonus. Subcortical and brainstem myoclonus can be treated with clonazepam as a first-line agent, but levetiracetam and valproic acid can be tried as well. l-5-Hydroxytryptophan and sodium oxybate are agents used for refractory cases. Spinal myoclonus does not respond to anti-epileptic drugs, and clonazepam is a first-line agent. Botulinum toxin treatment can be useful for focal cases of spinal myoclonus. The etiology of propriospinal myoclonus is controversial, and a functional etiology is suspected in most cases. Treatment can include clonazepam, levetiracetam, baclofen, valproate, carbamazepine, and zonisamide. Functional myoclonus requires multimodal and multidisciplinary treatment that may include psychotropic drugs and physical and occupational therapy. Close collaboration between neurologists and psychiatrists is required for effective treatment. Finally, deep brain stimulation targeting the globus pallidus pars-interna bilaterally has been used in myoclonus-dystonia when pharmacological treatments have been exhausted.

Keywords

Myoclonus Lance-Adams syndrome Medication-induced myoclonus Treatment Functional myoclonus Propriospinal myoclonus 

Notes

Compliance with Ethical Standards

Conflict of Interest

Ariel Levy declares no conflict of interest.

Robert Chen received research grant from Medtronic Inc, honorarium from Allergan, and research grant and honorarium from Merz.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Stanley Fahn JJ, Hallett M. Myoclonus: phenomenology, etiology, physiology, and treatment principles and practice of movement disorders. Edinburgh: Saunders; 2011. p. 447–64.Google Scholar
  2. 2.
    Ikeda A, Kakigi R, Funai N, et al. Cortical tremor: a variant of cortical reflex myoclonus. Neurology. 1990;40:1561–5.CrossRefPubMedGoogle Scholar
  3. 3.
    Stanley Fahn JJ, Hallett M. Principles and practice of movement disorders. Edinburgh: Saunders; 2011.Google Scholar
  4. 4.
    Caviness JN, Brown P. Myoclonus: current concepts and recent advances. Lancet Neurol. 2004;3:598–607.CrossRefPubMedGoogle Scholar
  5. 5.••
    Espay AJ, Chen R. Myoclonus. Continuum (Minneap Minn). 2013;19:1264–86. This review focuses on the etiology, diagnosis, and electrophysiological evaluation of myoclonus as well as treatment.Google Scholar
  6. 6.
    Kurian M, Lalive PH, Dalmau JO, et al. Opsoclonus-myoclonus syndrome in anti-N-methyl-D-aspartate receptor encephalitis. Arch Neurol. 2010;67:118–21.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Turner MR, Irani SR, Leite MI, et al. Progressive encephalomyelitis with rigidity and myoclonus: glycine and NMDA receptor antibodies. Neurology. 2011;77:439–43.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Erlich R, Morrison C, Kim B, et al. ANNA-2: an antibody associated with paraneoplastic opsoclonus in a patient with large-cell carcinoma of the lung with neuroendocrine features—correlation of clinical improvement with tumor response. Cancer Investig. 2004;22:257–61.CrossRefGoogle Scholar
  9. 9.
    Pike M. Opsoclonus-myoclonus syndrome. Handb Clin Neurol. 2013;112:1209–11.CrossRefPubMedGoogle Scholar
  10. 10.
    Ganos C, Kassavetis P, Erro R, et al. The role of the cerebellum in the pathogenesis of cortical myoclonus. Mov Disord. 2014;29:437–43.CrossRefPubMedGoogle Scholar
  11. 11.
    Terada K, Ikeda A, Van Ness PC, et al. Presence of bereitschaftspotential preceding psychogenic myoclonus: clinical application of jerk-locked back averaging. J Neurol Neurosurg Psychiatry. 1995;58:745–7.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.•
    Roze E, Bounolleau P, Ducreux D, et al. Propriospinal myoclonus revisited: clinical, neurophysiologic, and neuroradiologic findings. Neurology. 2009;72:1301–9. Article summarizes the clinical, electrophysiological, and neuroimaging features of propriosimal myoclonus. They report microstructual injuries that may explain some idiopathic cases.CrossRefPubMedGoogle Scholar
  13. 13.
    van der Salm SM, Erro R, Cordivari C, et al. Propriospinal myoclonus: clinical reappraisal and review of literature. Neurology. 2014;83:1862–70.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    van der Salm SM, Tijssen MA, Koelman JH, et al. The bereitschaftspotential in jerky movement disorders. J Neurol Neurosurg Psychiatry. 2012;83:1162–7.CrossRefPubMedGoogle Scholar
  15. 15.
    Caviness JN. The clinical neurophysiology of myoclonus. In: Hallet M, editor. Handbook of clinical neurophysiology. Amsterdam: Elsevier; 2003.Google Scholar
  16. 16.
    Calandra-Buonaura G, Alessandria M, Liguori R, et al. Hypnic jerks: neurophysiological characterization of a new motor pattern. Sleep Med. 2014;15:725–7.CrossRefPubMedGoogle Scholar
  17. 17.
    Caviness JN, Truong DD. Myoclonus. Handb Clin Neurol. 2011;100:399–420.CrossRefPubMedGoogle Scholar
  18. 18.
    Angel MJ, Young GB. Metabolic encephalopathies. Neurol Clin. 2011;29:837–82.CrossRefPubMedGoogle Scholar
  19. 19.
    Jimenez-Jimenez FJ, Puertas I, de Toledo-Heras M. Drug-induced myoclonus: frequency, mechanisms and management. CNS Drugs. 2004;18:93–104.CrossRefPubMedGoogle Scholar
  20. 20.
    Deik AF, Shanker VL. A case of amiodarone-associated myoclonus responsive to levetiracetam. Can J Neurol Sci. 2012;39:680–1.CrossRefPubMedGoogle Scholar
  21. 21.
    Brown P, Steiger MJ, Thompson PD, et al. Effectiveness of piracetam in cortical myoclonus. Mov Disord. 1993;8:63–8.CrossRefPubMedGoogle Scholar
  22. 22.
    Obeso JA, Artieda J, Quinn N, et al. Piracetam in the treatment of different types of myoclonus. Clin Neuropharmacol. 1988;11:529–36.CrossRefPubMedGoogle Scholar
  23. 23.
    Koskiniemi M, Van Vleymen B, Hakamies L, et al. Piracetam relieves symptoms in progressive myoclonus epilepsy: a multicentre, randomised, double blind, crossover study comparing the efficacy and safety of three dosages of oral piracetam with placebo. J Neurol Neurosurg Psychiatry. 1998;64:344–8.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Mbizvo GK, Dixon P, Hutton JL, et al. The adverse effects profile of levetiracetam in epilepsy: a more detailed look. Int J Neurosci. 2014;124:627–34.CrossRefPubMedGoogle Scholar
  25. 25.
    Striano P, Manganelli F, Boccella P, et al. Levetiracetam in patients with cortical myoclonus: a clinical and electrophysiological study. Mov Disord. 2005;20:1610–4.CrossRefPubMedGoogle Scholar
  26. 26.
    Frucht SJ, Bordelon Y, Houghton WH, et al. A pilot tolerability and efficacy trial of sodium oxybate in ethanol-responsive movement disorders. Mov Disord. 2005;20:1330–7.CrossRefPubMedGoogle Scholar
  27. 27.
    Genton P, Gelisse P. Antimyoclonic effect of levetiracetam. Epileptic Disord. 2000;2:209–12.PubMedGoogle Scholar
  28. 28.
    Lexicomp Online®. Accessed October 17th, 2015.Google Scholar
  29. 29.
    Shin JH, Park JM, Kim AR, et al. Lance-Adams syndrome. Ann Rehabil Med. 2012;36:561–4.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Frucht SJ, Houghton WC, Bordelon Y, et al. A single-blind, open-label trial of sodium oxybate for myoclonus and essential tremor. Neurology. 2005;65:1967–9.CrossRefPubMedGoogle Scholar
  31. 31.
    Menon MK. Antimyoclonic effect of sodium oxybate: clinical implications. JAMA. 1981;245:2495.CrossRefPubMedGoogle Scholar
  32. 32.
    Arpesella R, Dallocchio C, Arbasino C, et al. A patient with intractable posthypoxic myoclonus (Lance-Adams syndrome) treated with sodium oxybate. Anaesth Intensive Care. 2009;37:314–8.PubMedGoogle Scholar
  33. 33.
    Magnussen I, Dupont E, Engbaek F, et al. Post-hypoxic intention myoclonus treated with 5-hydroxy-tryptophan and an extracerebral decarboxylase inhibitor. Acta Neurol Scand. 1978;57:289–94.CrossRefPubMedGoogle Scholar
  34. 34.
    Van Woert MH, Sethy VH. Therapy of intention myoclonus with L-5-hydroxytryptophan and a peripheral decarboxylase inhibitor, MK 486. Neurology. 1975;25:135–40.CrossRefPubMedGoogle Scholar
  35. 35.
    Deuschl G, Wilms H. Palatal tremor: the clinical spectrum and physiology of a rhythmic movement disorder. Adv Neurol. 2002;89:115–30.PubMedGoogle Scholar
  36. 36.
    Zadikoff C, Lang AE, Klein C. The ‘essentials’ of essential palatal tremor: a reappraisal of the nosology. Brain. 2006;129:832–40.CrossRefPubMedGoogle Scholar
  37. 37.
    Stamelou M, Saifee TA, Edwards MJ, et al. Psychogenic palatal tremor may be underrecognized: reappraisal of a large series of cases. Mov Disord. 2012;27:1164–8.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.•
    Kern DS, Lang AE. Successful treatment of functional palatal tremor: insights into pathogenesis and management. Mov Disord. 2015;30:875–6. This report highlights the evolving understanding of essential palatal tremor (myoclonus) and its functional etiology.CrossRefPubMedGoogle Scholar
  39. 39.
    Nasr A, Brown N. Palatal myoclonus responding to lamotrigine. Seizure. 2002;11:136–7.CrossRefPubMedGoogle Scholar
  40. 40.
    Penney SE, Bruce IA, Saeed SR. Botulinum toxin is effective and safe for palatal tremor: a report of five cases and a review of the literature. J Neurol. 2006;253:857–60.CrossRefPubMedGoogle Scholar
  41. 41.
    Obeso JA. Therapy of myoclonus. Clin Neurosci. 1995;3:253–7.PubMedGoogle Scholar
  42. 42.
    Keswani SC, Kossoff EH, Krauss GL, et al. Amelioration of spinal myoclonus with levetiracetam. J Neurol Neurosurg Psychiatry. 2002;73:457–8.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Siniscalchi A, Mancuso F, Russo E, et al. Spinal myoclonus responsive to topiramate. Mov Disord. 2004;19:1380–1.CrossRefPubMedGoogle Scholar
  44. 44.
    Chiodo AE, Saval A. Intrathecal baclofen for the treatment of spinal myoclonus: a case series. J Spinal Cord Med. 2012;35:64–7.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Polo KB, Jabbari B. Effectiveness of botulinum toxin type A against painful limb myoclonus of spinal cord origin. Mov Disord. 1994;9:233–5.CrossRefPubMedGoogle Scholar
  46. 46.
    Lagueny A, Tison F, Burbaud P, et al. Stimulus-sensitive spinal segmental myoclonus improved with injections of botulinum toxin type A. Mov Disord. 1999;14:182–5.CrossRefPubMedGoogle Scholar
  47. 47.
    Vivancos-Matellano F, Arpa-Gutierrez FJ, Perez-Conde MC, et al. The effectiveness of Botulinum toxin type A in two cases of abdominal myoclonias refractory to conventional therapy. Rev Neurol. 2006;42:59–61.PubMedGoogle Scholar
  48. 48.
    Esposito M, Erro R, Edwards MJ, et al. The pathophysiology of symptomatic propriospinal myoclonus. Mov Disord. 2014;29:1097–9.CrossRefPubMedGoogle Scholar
  49. 49.
    Antelmi E, Provini F. Propriospinal myoclonus: the spectrum of clinical and neurophysiological phenotypes. Sleep Med Rev. 2015;22:54–63.CrossRefPubMedGoogle Scholar
  50. 50.
    Jang W, Kim JS, Ahn JY, et al. Reversible propriospinal myoclonus due to thoracic disc herniation: long-term follow-up. J Neurol Sci. 2012;313:32–4.CrossRefPubMedGoogle Scholar
  51. 51.
    Espay AJ, Ashby P, Hanajima R, et al. Unique form of propriospinal myoclonus as a possible complication of an enteropathogenic toxin. Mov Disord. 2003;18:942–8.CrossRefPubMedGoogle Scholar
  52. 52.••
    Erro R, Bhatia KP, Edwards MJ, et al. Clinical diagnosis of propriospinal myoclonus is unreliable: an electrophysiologic study. Mov Disord. 2013;28:1868–73. This article highlights that propriospinal myoclonus requires electrophysiological characterization and posists that the etiology in most cases may be functional.CrossRefPubMedGoogle Scholar
  53. 53.
    Maltete D, Verdure P, Roze E, et al. TENS for the treatment of propriospinal myoclonus. Mov Disord. 2008;23:2256–7.CrossRefPubMedGoogle Scholar
  54. 54.
    Hallett M. Psychogenic movement disorders: neurology and neuropsychiatry. Wolters Kluwer; 2005.Google Scholar
  55. 55.
    Baizabal-Carvallo JF, Fekete R. Recognizing uncommon presentations of psychogenic (functional) movement disorders. Tremor Other Hyperkinet Mov (N Y). 2015;5:279.Google Scholar
  56. 56.•
    Kompoliti K, Wilson B, Stebbins G, et al. Immediate vs. delayed treatment of psychogenic movement disorders with short term psychodynamic psychotherapy: randomized clinical trial. Parkinsonism Relat Disord. 2014;20:60–3. This article is a well designed randomized cross-over study that demonstrates that patients kept within the medical system and regularly evaluated by physicians with or without psychodynamic therapy can help treat functional movement disorders.CrossRefPubMedGoogle Scholar
  57. 57.
    Hinson VK, Weinstein S, Bernard B, et al. Single-blind clinical trial of psychotherapy for treatment of psychogenic movement disorders. Parkinsonism Relat Disord. 2006;12:177–80.CrossRefPubMedGoogle Scholar
  58. 58.
    Czarnecki K, Thompson JM, Seime R, et al. Functional movement disorders: successful treatment with a physical therapy rehabilitation protocol. Parkinsonism Relat Disord. 2012;18:247–51.CrossRefPubMedGoogle Scholar
  59. 59.
    Dallocchio C, Arbasino C, Klersy C, et al. The effects of physical activity on psychogenic movement disorders. Mov Disord. 2010;25:421–5.CrossRefPubMedGoogle Scholar
  60. 60.
    Jordbru AA, Smedstad LM, Klungsoyr O, et al. Psychogenic gait disorder: a randomized controlled trial of physical rehabilitation with one-year follow-up. J Rehabil Med. 2014;46:181–7.CrossRefPubMedGoogle Scholar
  61. 61.
    Edwards MJ, Stone J, Nielsen G. Physiotherapists and patients with functional (psychogenic) motor symptoms: a survey of attitudes and interest. J Neurol Neurosurg Psychiatry. 2012;83:655–8.CrossRefPubMedGoogle Scholar
  62. 62.
    Zesiewicz TA, Sullivan KL, Arnulf I, et al. Practice parameter: treatment of nonmotor symptoms of Parkinson disease: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2010;74:924–31.CrossRefPubMedGoogle Scholar
  63. 63.
    Kobayashi K, Katayama Y, Otaka T, et al. Thalamic deep brain stimulation for the treatment of action myoclonus caused by perinatal anoxia. Stereotact Funct Neurosurg. 2010;88:259–63.CrossRefPubMedGoogle Scholar
  64. 64.
    Yamada K, Sakurama T, Soyama N, et al. Gpi pallidal stimulation for Lance-Adams syndrome. Neurology. 2011;76:1270–2.CrossRefPubMedGoogle Scholar
  65. 65.
    Trottenberg T, Meissner W, Kabus C, et al. Neurostimulation of the ventral intermediate thalamic nucleus in inherited myoclonus-dystonia syndrome. Mov Disord. 2001;16:769–71.CrossRefPubMedGoogle Scholar
  66. 66.
    Azoulay-Zyss J, Roze E, Welter ML, et al. Bilateral deep brain stimulation of the pallidum for myoclonus-dystonia due to epsilon-sarcoglycan mutations: a pilot study. Arch Neurol. 2011;68:94–8.CrossRefPubMedGoogle Scholar
  67. 67.
    Magarinos-Ascone CM, Regidor I, Martinez-Castrillo JC, et al. Pallidal stimulation relieves myoclonus-dystonia syndrome. J Neurol Neurosurg Psychiatry. 2005;76:989–91.CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Starr PA. Deep brain stimulation for other tremors, myoclonus, and chorea. Handb Clin Neurol. 2013;116:209–15.CrossRefPubMedGoogle Scholar
  69. 69.••
    Rughani AI, Lozano AM. Surgical treatment of myoclonus dystonia syndrome. Mov Disord. 2013;28:282–7. This review of published cases compared different targets for functional neurosurgery in myoclonus dystonia syndrome. Both dystonia and myoclonus improved in their analysis. Globus pallidus targets improved dystonia to a greater extent than the thalamic one.CrossRefPubMedGoogle Scholar
  70. 70.
    Sidiropoulos C, Mestre T, Hutchison W, et al. Bilateral pallidal stimulation for sargoglycan epsilon negative myoclonus. Parkinsonism Relat Disord. 2014;20:915–8.CrossRefPubMedGoogle Scholar

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© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Division of Neurology, Department of MedicineUniversity of TorontoTorontoCanada
  2. 2.Morton and Gloria Shulman Movement Disorders CentreToronto Western HospitalTorontoCanada

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