Pediatric Drugs

, Volume 8, Issue 5, pp 303–310 | Cite as

Juvenile Myoclonic Epilepsy

Epidemiology, Pathophysiology, and Management
Review Article


Juvenile myoclonic epilepsy (JME) is a common epilepsy syndrome that begins most frequently in the early teenage years. It is officially classified as a type of idiopathic generalized epilepsy and is often under-recognized or misdiagnosed. This syndrome has a strong genetic component with multiple gene mutations being associated with the clinical presentation. Based upon genetic associations, there may be multiple pathophysiologic mechanisms for the disorder; the pathophysiology has not been clearly defined.

A diagnosis of JME is made using the clinical history and EEG findings. Valproic acid is the primary antiepileptic drug (AED) used for JME, but some newer AEDs may be effective alternatives. Selection of an appropriate AED is essential to the proper management of JME, because of the possibility of exacerbation of seizures by some AEDs and the adverse effect profiles of effective drugs. It is important for clinicians to understand JME to correctly diagnose and manage patients with this syndrome.



No sources of funding were used to assist in the preparation of this review. The author has served as a consultant for or received grant funds from Medpointe Pharmaceuticals, Ovation Pharmaceuticals, Elan Pharmaceuticals, Abbott Pharmaceuticals, and GlaxoSmithKline Pharmaceuticals.


  1. 1.
    Eadie MJ. The epileptology of Theodore Herpin (1799–1865). Epilepsia 2002; 43(10): 1256–61PubMedCrossRefGoogle Scholar
  2. 2.
    International League Against Epilepsy. Epilepsy syndromes and related conditions [online]. Available from URL: [Accessed 2006 Sep 12]
  3. 3.
    Hauser WA, Annegers JF, Rocca WA. Descriptive epidemiology of epilepsy: contributions of population-based studies from Rochester, Minnesota. Mayo Clin Proc 1996; 71(6): 576–86PubMedCrossRefGoogle Scholar
  4. 4.
    Genton P, Gelisse P. Juvenile myoclonic epilepsy. Arch Neurol 2001; 58(9): 1487–90PubMedCrossRefGoogle Scholar
  5. 5.
    Hauser WA. Epidemiology of epilepsy in children. In: Pellock JM, Dodson WE, Bourgeois FD, editors. Pediatric epilepsy diagnosis and treatment. New York: Demos, 2001: 81–96Google Scholar
  6. 6.
    Obeid T, Panayiotopoulos CP. Juvenile myoclonic epilepsy: a study in Saudi Arabia. Epilepsia 1988; 29(3): 280–2PubMedCrossRefGoogle Scholar
  7. 7.
    Nair RR, Thomas SV. Genetic liability to epilepsy in Kerala State, India. Epilepsy Res 2004; 62(2–3): 163–70PubMedCrossRefGoogle Scholar
  8. 8.
    Liu AW, Delgador-Escueta AV, Gee MN, et al. Juvenile myoclonic epilepsy in chromosome 6p12–p11: locus heterogeneity and recombinations. Am J Med Genet 1996; 63(3): 438–46PubMedCrossRefGoogle Scholar
  9. 9.
    Escayg A, De Waard M, Lee DD, et al. Coding and noncoding variation of the human calcium-channel beta4-subunit gene CACNB4 in patients with idiopathic generalized epilepsy and episodic ataxia. Am J Hum Genet 2000; 66(5): 1531–9PubMedCrossRefGoogle Scholar
  10. 10.
    Cossette P, Liu L, Brisebois K, et al. Mutation of GABRA1 in an autosomal dominant form of juvenile myoclonic epilepsy. Nat Genet 2002; 31(2): 184–9PubMedCrossRefGoogle Scholar
  11. 11.
    Peters HC, Kammer G, Volz A, et al. Mapping, genomic structure, and polymorphisms of the human GABABR1 receptor gene: evaluation of its involvement in idiopathic generalized epilepsy. Neurogenetics 1998; 2(1): 47–54PubMedCrossRefGoogle Scholar
  12. 12.
    Haug K, Sander T, Hallmann K, et al. The voltage-gated sodium channel beta2-subunit gene and idiopathic generalized epilepsy. Neuroreport 2000; 11(12): 2687–9PubMedCrossRefGoogle Scholar
  13. 13.
    Suzuki T, Delgado-Escueta AV, Aguan K, et al. Mutations in EFHC1 cause juvenile myoclonic epilepsy. Nat Genet 2004; 36(8): 842–9PubMedCrossRefGoogle Scholar
  14. 14.
    Wong CG, Scherer SW, Snead 3rd OC, et al. Localization of the human mGluR4 gene within an epilepsy susceptibility locus (1). Brain Res Mol Brain Res 2001; 87(1): 109–16PubMedCrossRefGoogle Scholar
  15. 15.
    Vijai J, Kapoor A, Ravishankar HM, et al. Genetic association analysis of KCNQ3 and juvenile myoclonic epilepsy in a South Indian population. Hum Genet 2003; 113(5): 461–3PubMedCrossRefGoogle Scholar
  16. 16.
    Taske NL, Williamson MP, Makoff A, et al. Evaluation of the positional candidate gene CHRNA7 at the juvenile myoclonic epilepsy locus (EJM2) on chromosome 15q13–14. Epilepsy Res 2002; 49(2): 157–72PubMedCrossRefGoogle Scholar
  17. 17.
    Bai D, Alonso ME, Medina MT, et al. Juvenile myoclonic epilepsy: linkage to chromosome 6p12 in Mexico families. Am J Med Genet 2002; 113(3): 268–74PubMedCrossRefGoogle Scholar
  18. 18.
    Pal DK, Evgrafov DV, Tabares P, et al. BRD2 (RING3) is a probable major susceptibility gene for common juvenile myoclonic epilepsy. Am J Hum Genet 2003; 73(2): 261–70PubMedCrossRefGoogle Scholar
  19. 19.
    Vijai J, Kapoor A, Ravishankar HM, et al. Protective and susceptibility effects of hSKCa3 allelic variants on juvenile myoclonic epilepsy. J Med Genet 2005; 42(5): 439–42PubMedCrossRefGoogle Scholar
  20. 20.
    Janz D. Epilepsy with impulsive petit mal (juvenile myoclonic epilepsy). Acta Neurol Scand 1985; 72(5): 449–59PubMedCrossRefGoogle Scholar
  21. 21.
    Dhanuka AK, Jain BK, Daljit S, et al. Juvenile myoclonic epilepsy: a clinical and sleep EEG study. Seizure 2001; 10(5): 374–8PubMedCrossRefGoogle Scholar
  22. 22.
    Penry JK, Dean JC, Riela AR. Juvenile myoclonic epilepsy: long-term response to therapy. Epilepsia 1989; 30Suppl. 4: S19–23PubMedCrossRefGoogle Scholar
  23. 23.
    Janz D, Christian W. Impulsiv-petit mal. Dtsch Z Nervenheilkd 1957; 176: 346–86Google Scholar
  24. 24.
    Castells B, Mendilaharsu C. La epilepsia mioclinica bilateral y consicente. Acta Neurol Latinoam 1958; 4: 23–48Google Scholar
  25. 25.
    Atakli D, Sozuer D, Atay T, et al. Misdiagnosis and treatment in juvenile myoclonic epilepsy. Seizure 1998; 7(1): 63–6PubMedCrossRefGoogle Scholar
  26. 26.
    Benbadis SR. Observations on the misdiagnosis of generalized epilepsy as partial epilepsy: causes and consequences. Seizure 1999; 8(3): 140–5PubMedCrossRefGoogle Scholar
  27. 27.
    Canevini MP, Mai R, Di Marco C, et al. Juvenile myoclonic epilepsy of Janz: clinical observations in 60 patients. Seizure 1992; 1(4): 291–8PubMedCrossRefGoogle Scholar
  28. 28.
    Montalenti E, Imperiale D, Rovera A, et al. Clinical features, EEG findings and diagnostic pitfalls in juvenile myoclonic epilepsy: a series of 63 patients. J Neurol Sci 2001; 184(1): 65–70PubMedCrossRefGoogle Scholar
  29. 29.
    Appleton RM, Beirne M, Acomb B. Photosensitivity in juvenile myoclonic epilepsy. Seizure 2000; 9(2): 108–11PubMedCrossRefGoogle Scholar
  30. 30.
    Schmidt D, Gram L. A practical guide to when (and how) to withdraw antiepileptic drugs in seizure-free patients. Drugs 1996; 52(6): 870–4PubMedCrossRefGoogle Scholar
  31. 31.
    Specchio LM, Beghi E. Should antiepileptic drugs be withdrawn in seizure-free patients? CNS Drugs 2004; 18(4): 201–12PubMedCrossRefGoogle Scholar
  32. 32.
    Shinnar S, Berg AT, Moshe SL, et al. Discontinuing antiepileptic drugs in children with epilepsy: a prospective study. Ann Neurol 1994; 35(5): 534–45PubMedCrossRefGoogle Scholar
  33. 33.
    Calleja S, Salas-Puig J, Ribacoba R, et al. Evolution of juvenile myoclonic epilepsy treated from the outset with sodium valproate. Seizure 2001; 10(6): 424–7PubMedGoogle Scholar
  34. 34.
    Bourgeois B, Beaumanoir A, Blajev B, et al. Monotherapy with valproate in primary generalized epilepsies. Epilepsia 1987; 28Suppl. 2: S8–11PubMedCrossRefGoogle Scholar
  35. 35.
    Karlovassitou-Koniari A, Alexiou D, Angelopoulos P, et al. Low dose sodium valproate in the treatment of juvenile myoclonic epilepsy. J Neurol 2002; 249(4): 396–9PubMedCrossRefGoogle Scholar
  36. 36.
    Sundqvist AT, Tomson T, Lundkvist B. Valproate as monotherapy for juvenile myoclonic epilepsy: dose-effect study. Ther Drug Monit 1998; 20(2): 149–57PubMedCrossRefGoogle Scholar
  37. 37.
    Corman CL, Leung NM, Guberman AH. Weight gain in epileptic patients during treatment with valproic acid: a retrospective study. Can J Neurol Sci 1997; 24(3): 240–4PubMedGoogle Scholar
  38. 38.
    Dinesen H, Gram L, Andersen T, et al. Weight gain during treatment with valproate. Acta Neurol Scand 1984; 70(2): 65–9PubMedCrossRefGoogle Scholar
  39. 39.
    Mattson RH, Cramer JA, Collins JF. A comparison of valproate with carbamazepine for the treatment of complex partial seizures and secondarily generalized tonic-clonic seizures in adults: the Department of Veterans Affairs Epilepsy Cooperative Study No. 264 Group. N Engl J Med 1992; 327(11): 765–71PubMedCrossRefGoogle Scholar
  40. 40.
    Isojarvi JI, Laatikainen TJ, Pakarinen AJ, et al. Polycystic ovaries and hyperandrogenism in women taking valproate for epilepsy. N Engl J Med 1993; 329(19): 1383–8PubMedCrossRefGoogle Scholar
  41. 41.
    O’Donovan C, Kusumakar V, Graves GR, et al. Menstrual abnormalities and polycystic ovary syndrome in women taking valproate for bipolar mood disorder. J Clin Psychiatry 2002; 63(4): 322–30PubMedCrossRefGoogle Scholar
  42. 42.
    Boluk A, Guzelipek M, Savli H, et al. The effect of valproate on bone mineral density in adult epileptic patients. Pharmacol Res 2004; 50(1): 93–7PubMedCrossRefGoogle Scholar
  43. 43.
    Sato Y, Kondo I, Ishida S, et al. Decreased bone mass and increased bone turnover with valproate therapy in adults with epilepsy. Neurology 2001; 57(3): 445–9PubMedCrossRefGoogle Scholar
  44. 44.
    Sheth RD, Wesolowski CA, Jacob JC, et al. Effect of carbamazepine and valproate on bone mineral density. J Pediatr 1995; 127: 256–62PubMedCrossRefGoogle Scholar
  45. 45.
    Drezner MK. Treatment of anticonvulsant drug-induced bone disease. Epilepsy Behav 2004; 5Suppl. 2: S41–7PubMedCrossRefGoogle Scholar
  46. 46.
    Kulak CA, Borba VZ, Bilezikian JP, et al. Bone mineral density and serum levels of 25 OH vitamin D in chronic users of antiepileptic drugs. Arq Neuropsiquiatr 2004; 62(4): 940–8PubMedCrossRefGoogle Scholar
  47. 47.
    Thomas SV, Indrani L, Devi GC, et al. Pregnancy in women with epilepsy: preliminary results of Kerala registry of epilepsy and pregnancy. Neurol India 2001; 49(1): 60–6PubMedGoogle Scholar
  48. 48.
    Vajda FJ, O’Brien TJ, Hitchcock A, et al. Critical relationship between sodium valproate dose and human teratogenicity: results of the Australian register of anti-epileptic drugs in pregnancy. J Clin Neurosci 2004; 11(8): 854–8PubMedCrossRefGoogle Scholar
  49. 49.
    Ethell BT, Anderson GD, Burchell B. The effect of valproic acid on drug and steroid glucuronidation by expressed human UDP-glucuronosyltransferases. Biochem Pharmacol 2003; 65(9): 1441–9PubMedCrossRefGoogle Scholar
  50. 50.
    Wen X, Wang JS, Kivisto KT, et al. In vitro evaluation of valproic acid as an inhibitor of human cytochrome P450 isoforms: preferential inhibition of cytochrome P450 2C9 (CYP2C9). Br J Clin Pharmacol 2001; 52(5): 547–53PubMedCrossRefGoogle Scholar
  51. 51.
    Anderson GD. A mechanistic approach to antiepileptic drug interactions. Ann Pharmacother 1998; 32(5): 554–63PubMedCrossRefGoogle Scholar
  52. 52.
    Gidal BE, Sheth R, Parnell J, et al. Evaluation of VPA dose and concentration effects on lamotrigine pharmacokinetics: implications for conversion to lamotrigine monotherapy. Epilepsy Res 2003; 57(2–3): 85–93PubMedCrossRefGoogle Scholar
  53. 53.
    Beran RG, Berkovic SF, Dunagan FM, et al. Double-blind, placebo-controlled, crossover study of lamotrigine in treatment-resistant generalised epilepsy. Epilepsia 1998; 39(12): 1329–33PubMedCrossRefGoogle Scholar
  54. 54.
    Morris GL, Hammer AE, Kustra RP, et al. Lamotrigine for patients with juvenile myoclonic epilepsy following prior treatment with valproate: results of an open-label study. Epilepsy Behav 2004; 5(4): 509–12PubMedCrossRefGoogle Scholar
  55. 55.
    Buchanan N. The use of lamotrigine in juvenile myoclonic epilepsy. Seizure 1996; 5(2): 149–51PubMedGoogle Scholar
  56. 56.
    Prasad A, Kuzniecky RI, Knowlton RC, et al. Evolving antiepileptic drug treatment in juvenile myoclonic epilepsy. Arch Neurol 2003; 60(8): 1100–5PubMedCrossRefGoogle Scholar
  57. 57.
    Biraben A, Allain H, Scarabin JM, et al. Exacerbation of juvenile myoclonic epilepsy with lamotrigine [letter]. Neurology 2000; 55(11): 1758PubMedCrossRefGoogle Scholar
  58. 58.
    Carrazana EJ, Wheeler SD. Exacerbation of juvenile myoclonic epilepsy with lamotrigine. Neurology 2001; 56(10): 1424–5PubMedCrossRefGoogle Scholar
  59. 59.
    Welty TE, Kuzniecky RI, Faught E. Newer antiepileptic drug outcomes in juvenile myoclonic epilepsy patients [abstract]. Epilepsia 2004; 45Suppl. 7: 145Google Scholar
  60. 60.
    Li LM, Russo M, O’Donoghue MF, et al. Allergic skin rash with lamotrigine and concomitant valproate therapy: evidence for an increased risk. Arq Neuropsiquiatr 1996; 54(1): 47–9PubMedCrossRefGoogle Scholar
  61. 61.
    Dooley J, Camfield P, Gordon K, et al. Lamotrigine-induced rash in children. Neurology 1996; 46(1): 240–2PubMedCrossRefGoogle Scholar
  62. 62.
    Guberman AH, Besag FM, Brodie MJ, et al. Lamotrigine-associated rash: risk/benefit considerations in adults and children. Epilepsia 1999; 40(7): 985–91PubMedCrossRefGoogle Scholar
  63. 63.
    Wheless JW. Use of topiramate in childhood generalized seizure disorders. J Child Neurol 2000; 15Suppl. 1: S7–13PubMedCrossRefGoogle Scholar
  64. 64.
    Ben-Zeev B, Watemberg N, Augarten A, et al. Oligohydrosis and hyperthermia: pilot study of a novel topiramate adverse effect. J Child Neurol 2003; 18(4): 254–7PubMedCrossRefGoogle Scholar
  65. 65.
    Lamb EJ, Stevens PE, Nashef L. Topiramate increases biochemical risk of nephrolithiasis. Ann Clin Biochem 2004; 41 (Pt 2): 166–9PubMedCrossRefGoogle Scholar
  66. 66.
    Antai-Otong D. Mitigating cognitive side effects associated with topiramate. Perspect Psychiatr Care 2005; 41(2): 92–3PubMedCrossRefGoogle Scholar
  67. 67.
    Kockelmann E, Elger CE, Helmstaedter C. Cognitive profile of topiramate as compared with lamotrigine in epilepsy patients on antiepileptic drug polytherapy: relationships to blood serum levels and comedication. Epilepsy Behav 2004; 5(5): 716–21PubMedCrossRefGoogle Scholar
  68. 68.
    Yamauchi T, Aikawa H. Efficacy of zonisamide: our experience. Seizure 2004; 13Suppl. 1: S41–8PubMedCrossRefGoogle Scholar
  69. 69.
    Yagi K. Overview of Japanese experience: controlled and uncontrolled trials. Seizure 2004; 13Suppl. 1: S11–5PubMedCrossRefGoogle Scholar
  70. 70.
    Kothare SV, Valencia I, Khurana DS, et al. Efficacy and tolerability of zonisamide in juvenile myoclonic epilepsy. Epileptic Disord 2004; 6(4): 267–70PubMedGoogle Scholar
  71. 71.
    Knudsen JF, Thambi LR, Kapcala LP, et al. Oligohydrosis and fever in pediatric patients treated with zonisamide. Pediatr Neurol 2003; 28: 184–9PubMedCrossRefGoogle Scholar
  72. 72.
    Eisai Inc. Zonegran full prescribing information [online]. Available from URL: [Accessed 2006 Sep 12]
  73. 73.
    Krauss GL, Betts T, Abou-Khalil B, et al. Levetiracetam treatment of idiopathic generalised epilepsy. Seizure 2003; 12(8): 617–20PubMedCrossRefGoogle Scholar
  74. 74.
    Kumar SP, Smith PE. Levetiracetam as add-on therapy in generalised epilepsies. Seizure 2004; 13(7): 475–7PubMedCrossRefGoogle Scholar
  75. 75.
    Cohen J. Levetiracetam monotherapy for primary generalised epilepsy. Seizure 2003; 12(3): 150–3PubMedCrossRefGoogle Scholar
  76. 76.
    Obeid T, Panayiotopoulos CP. Clonazepam in juvenile myoclonic epilepsy. Epilepsia 1989; 30(5): 603–6PubMedCrossRefGoogle Scholar
  77. 77.
    Panayiotopoulos CP, Obeid T, Tahan AR. Juvenile myoclonic epilepsy: a 5-year prospective study. Epilepsia 1994; 35(2): 285–96PubMedCrossRefGoogle Scholar
  78. 78.
    Lance JW, Anthony M. Sodium valproate and clonazepam in the treatment of intractable epilepsy. Arch Neurol 1977; 34(1): 14–7PubMedCrossRefGoogle Scholar
  79. 79.
    Mireles R, Leppik IE. Valproate and clonazepam comedication in patients with intractable epilepsy. Epilepsia 1985; 26(2): 122–6PubMedCrossRefGoogle Scholar
  80. 80.
    Specht U, Boenigk HE, Wolf P. Discontinuation of clonazepam after long-term treatment. Epilepsia 1989; 30(4): 458–63PubMedCrossRefGoogle Scholar
  81. 81.
    Wheless JW. Acute management of seizures in the syndromes of idiopathic generalized epilepsies. Epilepsia 2003; 44Suppl. 2: 22–6PubMedCrossRefGoogle Scholar
  82. 82.
    Murphy K, Delanty N. Primary generalized epilepsies. Curr Treat Options Neurol 2000; 2(6): 527–42PubMedCrossRefGoogle Scholar
  83. 83.
    Clobazam in treatment of refractory epilepsy: the Canadian experience: a retrospective study. Canadian Clobazam Cooperative Group. Epilepsia 1991; 32(3): 407–16Google Scholar
  84. 84.
    Perez J, Chiron C, Musial C, et al. Stiripentol: efficacy and tolerability in children with epilepsy. Epilepsia 1999; 40(11): 1618–26PubMedCrossRefGoogle Scholar
  85. 85.
    Ernst JP, Doose H, Baier WK. Bromides were effective in intractable epilepsy with generalized tonic-clonic seizures and onset in early childhood. Brain Dev 1988; 10(6): 385–8PubMedCrossRefGoogle Scholar
  86. 86.
    Luna D, Dulac O, Pajot N, et al. Vigabatrin in the treatment of childhood epilepsies: a single-blind placebo-controlled study. Epilepsia 1989; 30(4): 430–7PubMedCrossRefGoogle Scholar
  87. 87.
    Hurst DL. Methsuximide therapy of juvenile myoclonic epilepsy. Seizure 1996; 5(1): 47–50PubMedCrossRefGoogle Scholar
  88. 88.
    Lerman P, Nussbaum E. The use of sulthiame: in myoclonic epilepsy of childhood and adolescence. Acta Neurol Scand Suppl 1975; 60: 7–12PubMedCrossRefGoogle Scholar
  89. 89.
    Genton P, Gelisse P, Thomas P, et al. Do carbamazepine and phenytoin aggravate juvenile myoclonic epilepsy? Neurology 2000; 55(8): 1106–9PubMedCrossRefGoogle Scholar
  90. 90.
    Perucca E, Gram L, Avanzini G, et al. Antiepileptic drugs as a cause of worsening seizures. Epilepsia 1998; 39(1): 5–17PubMedCrossRefGoogle Scholar
  91. 91.
    Genton P. When antiepileptic drugs aggravate epilepsy. Brain Dev 2000; 22(2): 75–80PubMedCrossRefGoogle Scholar

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© Adis Data Information BV 2006

Authors and Affiliations

  1. 1.Department of Pharmacy Practice, McWhorter School of PharmacySamford UniversityBirminghamUSA
  2. 2.Department of Neurology, College of MedicineUniversity of Alabama at BirminghamBirminghamUSA

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