Skip to main content

Advertisement

SpringerLink
Log in

Progressive myoclonic epilepsies

  • Published:
Current Treatment Options in Neurology Aims and scope Submit manuscript

Opinion statement

  • The treatment of progressive myoclonus epilepsy (PME) remains a major therapeutic challenge in neurology. Generalized convulsive seizures are often well controlled through classic antiepileptic drugs (AEDs) like valproate and clonazepam, whereas myoclonus, the main symptom that is affecting patients most in their daily life, is usually refractory to standard AEDs.

  • Alternative therapy concepts have been and still are investigated. Among the new drugs, zonisamide and piracetam have shown the most promising results as add-on treatments. Other therapeutic approaches, like the use of antioxidants,

  • 5-hydroxytryptophan (5-HTP), and baclofen should also be taken into consideration for the treatment of intractable cases of PME.

  • Nonpharmacologic treatment options such as diet and physical therapy should always be considered, because they may save costs and side effects.

  • In some instances, the occasional use of alcohol has shown beneficial effects.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Berkovic SF, Andermann F, Carpenter S, Wolfe LS: Progressive myoclonus epilepsies: specific causes and diagnosis. N Engl J Med 1986, 315(5):296–305.

    Article  PubMed  CAS  Google Scholar 

  2. Tate E: The clinical challenge of progressive myoclonus epilepsy. Nurse Pract 1993, 18(5):25–28.

    Article  PubMed  CAS  Google Scholar 

  3. Delgado-Escueta AV, Serratosa JM, Medina MT: Myoclonic seizures and progressive myoclonus epilepsy syndromes. In The Treatment of Epilepsy: Principles and Practice, edn 2. Edited by Wyllie E. Williams & Wilkins: Baltimore; 1997:467–483.

    Google Scholar 

  4. Yamakawa K, Mitchell S, Hubert R, et al.: Isolation and characterization of a candidate gene for progressive myoclonus epilepsy on 21q22.3. Hum Mol Genet 1995, 4:709–716.

    Article  PubMed  CAS  Google Scholar 

  5. Serratosa JM, Delgado-Escueta AV, Posada I, et al.: The gene for progressive myoclonus epilepsy of the Lafora type maps to chromosome 6q. Hum Mol Genet 1995, 4:1657–1663.

    Article  PubMed  CAS  Google Scholar 

  6. Ohisalo JJ, Murros K, Fredholm BB, Hare TA: Concentrations of g-aminobutyric acid and adenosine in the CSF in progressive myoclonus epilepsy without Lafora bodies. Arch Neurol 1983, 40:623–625.

    PubMed  CAS  Google Scholar 

  7. Leino E, MacDonald E, Airaksinen MM, Riekinen PJ: Homovanilic acid and 5-hydroxyindolacetic acid levels in cerebrospinal fluid of patients with progressive myoclonus epilepsy. Acta Neurol Scand 1980, 62:41–54.

    PubMed  CAS  Google Scholar 

  8. Iivanainen M, Eldrige R: Effect of phenytoin on the mental and physical function of patients with Baltic myoclonus epilepsy. Ital J Neurol Sci 1987, 8(4):313–317.

    Article  PubMed  CAS  Google Scholar 

  9. Halliday AM: Cerebral evoked potentials in familial progressive myoclonic epilepsy. J Royal Coll Phys Lond 1:123–134.

  10. Shibasaki H, Yamashita Y, Kuroiwa Y: Myoclonusrelated cortical spikes and high amplitude somatosensory evoked potentials. Brain 1978, 101:447–460.

    Article  PubMed  CAS  Google Scholar 

  11. Shibasaki H, Yamashita Y, Neshige R, et al.: Pathogenesis of giant somatosensory evoked potentials in progressive myoclonic epilepsy. Brain 1985, 108:225–240.

    Article  PubMed  Google Scholar 

  12. Bressman S, Fahn S, Eisenberg M, et al.: Biotinresponsive encephalopathy with myoclonus, ataxia, and seizures. In Advances in Neurology, vol 43: Myoclonus. Edited by Fahn S. New York: Raven Press; 1986:119–125.

    Google Scholar 

  13. Thoene JG, Lemons R, Baker H: Impaired intestinal absorption of biotin in juvenile multiple carboxylase deficiency. N Engl J Med 1983, 308(11):639–642.

    Article  PubMed  CAS  Google Scholar 

  14. Wolf B, Heard GS, McVoy JRS, Grier RE: Biotinidase deficiency. Ann NY Acad Sci 1985, 252–262.

  15. Wilder RM: The effects of ketonemia on the course of epilepsy. Mayo Clin Bull 1921, 2:307–308.

    Google Scholar 

  16. Davidian NM, Butler TM, Poole DT: The effect of ketosis induced by medium chain triglycerides on intracellular pH of mouse brain. Epilepsia 1978, 19:396–378.

    Google Scholar 

  17. Livingston S: Comprehensive Management of Epilepsy in Infancy, Childhood, and Adolescence, edn 1. Springfield: Charles C. Thomas Publishers; 1972.

    Google Scholar 

  18. Uthman BM, Beydoun A: Less commonly used antiepileptic therapies. In The Treatment of Epilepsy: Principles and Practice, edn 2. Edited by Wyllie E. Baltimore: Williams & Wilkins; 1997:937–953.

    Google Scholar 

  19. Freeman JM, Viling EPG: Seizures decrease rapidly after fasting. Arch Pediatr Adoesc Med 1999, 153:946–949. A recent trial in 17 children evaluating the decrease in atonic and myoclonic seizures during the use of a ketogenic diet. To provide an objective method of counting seizures, an ambulatory 24-hour EEG was used in this study.

    CAS  Google Scholar 

  20. Chan AWK: Alcohol and epilepsy. Epilepsia 1985, 26:323–333.

    PubMed  CAS  Google Scholar 

  21. Jain S, Jain M: Action myoclonus (Lance-Adams syndrome) secondary to strangulation with dramatic response to alcohol. Mov Disord 1991, 6:183.

    Article  PubMed  CAS  Google Scholar 

  22. Genton P, Guerrini R: Antimyoclonic effects of alcohol in progressive myoclonus epilepsy. Neurology 1990, 40(9):1412–1416.

    PubMed  CAS  Google Scholar 

  23. Lu CS, Chu NS: Effects of alcohol on myoclonus and somatosensory evoked potentials in dyssinergia cerebellaris.J Neurol Neurosurg Psychiatry 1991, 54:905–908.

    PubMed  CAS  Google Scholar 

  24. Hsiao MC, Liu CY, Yang YY, et al.: Progressive myoclonus epilepsies syndrome (Ramsay Hunt syndrome) with mental disorder: report of two cases. Psych Clin Neurosci 1999, 53:575–578.

    Article  CAS  Google Scholar 

  25. Dean JC: Valproate. In The Treatment of Epilepsy: Principles and Practice, edn 2. Edited by Wyllie E. Williams & Wilkins: Baltimore; 1997: 824–832.

    Google Scholar 

  26. Fariello R, Varasi M, Smith MC: Valproate: mechanism of action. In Antiepileptic Drugs, edn 4. Edited by Levy R, Mattson RH, Meldrum BS, et al. New York: Raven Press; 1995:581–588.

    Google Scholar 

  27. Iivanainen M, Himberg JJ: Valproate and clonazepam in the treatment of severe progressive myoclonus epilepsy. Arch Neurol 1982, 39(4):236–238.

    PubMed  CAS  Google Scholar 

  28. Kyllerman M, Ben-Menachem E: Zonisamide for progressive myoclonus epilepsy: long term observations in seven patients. Epilepsy Res 1998, 29(2):109–114. A recent article describing the long term results of treating 7 PME patients (six Unverricht-Lundborg disease and one with Lafora’s) with a new AED, zonisamide. The authors are particularly impressed with the dramatic effect of zonisamide on myoclonus in 5 of the 7 patients.

    Article  PubMed  CAS  Google Scholar 

  29. De Gatta MRF, Gonzales ACA, Sanchez MJG, et al.: Effect of sodium valproate on phenobarbital serum levels in children and adults. Ther Drug Monit 1986, 8:416–420.

    Article  Google Scholar 

  30. Clancy RR: Valproate: an update - the challenge of modern pediatric seizure management. Curr Probl Pediatr 1990, 20:161–233.

    Article  PubMed  CAS  Google Scholar 

  31. Jeavons PM, Clark JE: Sodium valproate in the treatment of epilepsy. Br Med J 1974, 2:584–586.

    PubMed  CAS  Google Scholar 

  32. Dean JC, Penry JK: Weight gain patterns in patients with epilepsy: comparison of antiepileptic drugs. Epilepsia 1995, 36(suppl 4):72.

    Google Scholar 

  33. Haefely W: Benzodiazepines: mechanism of action. In Anitepileptic Drugs, edn 3. Edited by Levy RH, Dreifuss FE, Mattson RH, et al. New York: Raven Press; 1989:721–734.

    Google Scholar 

  34. Nanda RN, Johnson RH, Koegh HJ, et al.: Treatment of epilepsy with clonazepam and its effect on other anticonvulsants. J Neurol Neurosurg Psychiatry 1977, 40:538–543.

    PubMed  CAS  Google Scholar 

  35. Obeid T, Panayiotopoulos CP: Clonazepam in juvenile myoclonic epilepsy. Epilepsia 1989, 30(5):603–606.

    PubMed  CAS  Google Scholar 

  36. Browne TR: Clonazepam. N Engl J Med 1978, 299:812–816.

    Article  PubMed  CAS  Google Scholar 

  37. Bourgeois BFD: Phenobarbital and primidone. In The Treatment of Epilepsy: Principles and Practice, edn 2. Edited by Wyllie E. Baltimore: Williams & Wilkins; 1997:845–855.

    Google Scholar 

  38. MacDonald RL, Twyman RE: Kinetic properties and regulation of GABA receptor channels. In Ion Channels. Edited by Narahshi R. New York: Plenum Press; 1992:315–343.

    Google Scholar 

  39. Heyer EJ, MacDonald RL: Barbiturate reduction of calcium-dependent action potentials: correlation with anesthetic action. Brain Res 1982, 236:157–171.

    Article  PubMed  CAS  Google Scholar 

  40. Davis AG, Mutchie KD, Thompson JA, Myers GG: Once-daily dosing with phenobarbital in children with seizure disorders. Pediatrics 1981, 68:824–827.

    PubMed  CAS  Google Scholar 

  41. Lees G, Leach MJ: Studies on the mechanism of action of the novel anticonvulsant lamotrigine (Lamictal) using primary neuroglial cultures from rat cortex. Brain Res 1993, 612:190–199.

    Article  PubMed  CAS  Google Scholar 

  42. Wallace SJ: Myoclonus and epilepsy in childhood: a review of treatment with valproate, ethosiximide, lamotrigine, and zonisamide. Epilepsy Res 1998, 29(2):147–154. An article reviewing 4 AEDs (two classical and two new drugs) in the treatment of myoclonus epilepsy (PME and other conditions) in pediatric patients.

    Article  PubMed  CAS  Google Scholar 

  43. Santavuori P, Himberg JJ, Ahola A, et al.: Lamotrigine therapy in infantile ceroid lipofuscinosis. Epilepsia 1995, 36(suppl 3):S264.

    Google Scholar 

  44. Guerrini R, Dravet C, Genton P, et al.: Lamotrigine and seizure aggravation in severe myoclonic epilepsy. Epilepsia 1998, 39(5):508–512.

    Article  PubMed  CAS  Google Scholar 

  45. Anderson GD, Gidal BE, Levy RH, et al.: Effect of lamotrigine on the pharmacokinetics and biotransformation of valproate. Epilepsia 1991, 32(suppl 3):82.

    Google Scholar 

  46. Fisher R: Newer antiepileptic drugs. In The Treatment of Epilepsy: Principles and Practice, edn 2. Edited by Wyllie E. Baltimore: Williams & Wilkins; 1997:920–930.

    Google Scholar 

  47. Coulter D, Sombati S, DeLorenzo RJ: Selective effects of topiramate on sustained repetetive findings and spontaneous bursting in cultured hippocampal neurons. Epilepsia 1993, 34:123.

    Google Scholar 

  48. Uldall P, Bucholt JM: Clinical experiences with topiramate in children with intractable epilepsy. Euro J Ped Neurol 1999, 3(3):105–111. A recent open, add-on trial with topiramate in 39, mostly mentally retarded children with intractable epilepsy syndromes. One of the two PME patients included in the study showed dramatic clinical improvements.

    Article  CAS  Google Scholar 

  49. Leppik IE: Zonisamide. Epilepsia 1999, 40(suppl 5):S23-S29. A very recent review of the new AED zonisamide, with special interest in regards to pharmacologic basics and clinical use of this drug, including drug interactions and adverse events. The potency of zonisamide in the treatment of PME is outlined.

    Article  PubMed  CAS  Google Scholar 

  50. Suzuki S, Kawakami K, Nishimura S, et al.: Zonisamide blocks T-type calcium channel in cultured neurons of rat cerebral cortex. Epilepsy Res 1992, 12:21–27.

    Article  PubMed  CAS  Google Scholar 

  51. Mimaki T, Suzuki S, Tagawa T, et al.: Zonisamide binding in rat brain. Jpn J Psychiatry Neurol 1998, 42:640–642.

    Google Scholar 

  52. Henry TR, Leppik IE, Gumnit RJ, Jacobs M: Progressive myoclonus epilepsy treated with zonisamide. Neurology 1988, 38:928–931.

    PubMed  CAS  Google Scholar 

  53. NDA 20-789; Zonegram (zonisamide) Capsules 100mg [FDA approved labeling text]. San Francisco, CA: Elan Pharmaceuticals Inc; 2000.

  54. Kimura M, Tanaka N, Kimura Y, et al.: Pharmacokinetic interaction of zonisamide in rats: effect of other antiepiletics on zonisamide. J Pharmacobio Dynam 1992, 15:631–639.

    CAS  Google Scholar 

  55. Ojemann LM, Shastri RA, Wilensky AJ, et al.: Comparative pharmacokinetics of zonisamide in epileptic patients on carbamazepine or phenytoin monotherapy. Ther Drug Monit 1986, 8:293–296.

    PubMed  CAS  Google Scholar 

  56. Mueller WE, Koch S, Scheuer K, et al.: Effects of piracetam on membrane fluidity in the aged mouse, rat, and human brain. Biochem Pharmaco 1997, 53:135–140.

    Article  CAS  Google Scholar 

  57. Peuvot J, Schanck A, Deleers M, Brasseur R: Piracetam induced changes to membran physical properties. Biochem Pharmacol 1995, 50:1129–1134.

    Article  PubMed  CAS  Google Scholar 

  58. Bick RL: In vivo platelet inhibition by piracetam [letter]. Lancet 1979, 8145:752–753.

    Article  Google Scholar 

  59. Pepeu G, Spignoli G: Neurochemichal actions of ‘nootropic drugs’. In Alzheimer’s Disease. Edited by Wirtman RJ, Corkin S, Growdon JH, Ritter-Walker E. New York: Raven; 1990:247–252.

    Google Scholar 

  60. Obeso JA, Artieda J, Luquin MR, et al.: Antimyoclonic action of piracetam. Clin Neuropharmacology 1986, 9(1):58–64.

    Article  CAS  Google Scholar 

  61. Ikeda A, Shibasaki H, Tashiro K, et al.: Clinical trial of piracetam in patients with myoclonus: nationwide multiinstitution study in Japan. Mov Disord 1996, 11(6):691–700.

    Article  PubMed  CAS  Google Scholar 

  62. 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 vs. placebo. J Neurol Neurosurg Psychiatry 1998, 64:344–348. A recent multicenter, randomized, double-blind, crossover trial demonstrating a dose-effect relationship between piracetam and its beneficial effect on 20 patients with the classical Unverricht-Lundborg disease. The ratings of stimulus sensitivity, functional disability, handwriting, and global assessment were included in measuring outcome.

    Article  PubMed  CAS  Google Scholar 

  63. Paulus W, Ried S, Stodieck SR, Schmidt D: Abolition of photoparoxysmal response in progressive myoclonus epilepsy. Eur.Neurol 1991, 31(6):388–390.

    PubMed  CAS  Google Scholar 

  64. Koskiniemi M, Hyyppa M, Sainio K, et al.: Transient effect of L-tryptophan in progressive myoclonus epilepsy without Lafora bodies: clinical and electrophysiological study. Epilepsia 1980, 21:351–357.

    PubMed  CAS  Google Scholar 

  65. Van Woert MH, Rosenbaum D, Howieson J, Bowers MB Jr: Long-term therapy of myoclonus and other neurologic disorders with L-5-hydroxytryptophan and carbidopa. N Engl J Med 1977, 296(2):70–75.

    Article  PubMed  Google Scholar 

  66. Pranzatelli MR, Tate E, Huang Y, et al.: Neuropharmacology of progressive myoclonus epilepsy: response to 5-hydroxy-L-tryptophan. Epilepsia 1995, 36 (8):783–791.

    Article  PubMed  CAS  Google Scholar 

  67. Brownstein M: Neurotransmitter and hypothalamic hormones in the central nervous system. Fed Proc 1977, 36:1960–1963.

    PubMed  CAS  Google Scholar 

  68. Sobue I, Yamamota H, Kanagawa M, et al.: Effects of thyrotropin releasing hormone on ataxia of spincerebellar degeneration. Lancet 1980, 1:418–419.

    Article  PubMed  CAS  Google Scholar 

  69. Tanaka C, Maegaki Y, Koeda T, et al.: Successful treatment of progressive myoclonus epilepsy with TRH. Pediatr Neurol 1998, 18(5):442–444.

    Article  PubMed  CAS  Google Scholar 

  70. Inanaga K, Inoue Y: Effect of thyrotropin releasing hormone analog in a patient with myoclonus epilepsy. Kurume Med J 1981, 28:201–210.

    PubMed  CAS  Google Scholar 

  71. Prange AJ, Wilson IC: Thyrotropin releasing hormone for the immediate relief of depression. Psychopharmacology 1972, 28(suppl):82–87.

    Google Scholar 

  72. Hurd RW, Wilder BJ, Perchalski RJ: Increased extracellular superoxide dismutase in Baltic myoclonus. Epilepsia 1993, 34(suppl 2):14–15.

    Google Scholar 

  73. Hurd RW, Wilder BJ, Helveston WR, Uthman BM: Treatment of four siblings with progressive myoclonus epilepsy of the Unverricht Lundborg type with N acetylcysteine. Neurology 1996 Nov; 47 (5): 1264–1268. A brief report describing the beneficial effect of N-acetylcysteine (NAC) in four siblings with PME of the Unverricht-Lundborg type. Doses of NAC and supplemental vitamins and trace metals are mentioned.

    PubMed  CAS  Google Scholar 

  74. Selwa LM: N-acetylcysteine for Unverricht-Lundborg disease. Neurology 1999, 52(2):426–427.

    PubMed  CAS  Google Scholar 

  75. Awaad Y, Fish I: Baclofen in the treatment of polymyoclonus in a patient with Unverricht Lundborg disease. J Child Neurol 1995, 10(1):68–70.

    PubMed  CAS  Google Scholar 

  76. Bartholini G: GABA receptor agonist: Pharmacological spectrum and therapeutic actions. Med Res Rev 1985, 5:55–75.

    Article  PubMed  CAS  Google Scholar 

  77. Horowski R, Wachtel H: Direct dopaminergic action of lisuride hydrogen maleate, an ergot derivate in mice. Eur J Pharmacol 1976, 36:373–383.

    Article  PubMed  CAS  Google Scholar 

  78. Obeso JA, Rothwell JC, Quinn NP, et al.: Lisuride in the treatment of myoclonus. In Myoclonus: Advances in Neurology, vol 43. Edited by Fahn S, Marsden CD, Van Woert MH. New York: Raven Press; 1986:191–196.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology and Neurosciences, Malcom Randall Veterans Affairs Medical Center, Neurology Service (127), University of Florida College of Medicine, 1601 SW Archer Road, 32608, Gainesville, FL, USA

    Basim M. Uthman MD & Andreas Reichl MD

Authors
  1. Basim M. Uthman MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andreas Reichl MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Uthman, B.M., Reichl, A. Progressive myoclonic epilepsies. Curr Treat Options Neurol 4, 3–17 (2002). https://doi.org/10.1007/s11940-002-0001-9

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11940-002-0001-9

Keywords

Search

Navigation