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. 1998 Mar;64(3):344–348. doi: 10.1136/jnnp.64.3.344

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

M Koskiniemi 1, B Van Vleymen 1, L Hakamies 1, S Lamusuo 1, J Taalas 1
PMCID: PMC2169975  PMID: 9527146

Abstract

OBJECTIVE—To compare the efficacy, tolerability, and safety of three daily dosage regimens of oral piracetam in patients with progressive myoclonus epilepsy.
METHODS—Twenty patients (12 men, eight women), aged 17-43 years, with classical Unverricht-Lundborg disease were enrolled in a multicentre, randomised, double blind trial of crossover design in which the effects of daily doses of 9.6 g, 16.8 g, and 24 g piracetam, given in two divided doses, were compared with placebo. The crossover design was such that patients received placebo and two of the three dosage regimens of piracetam, each for two weeks, for a total treatment period of six weeks and thus without wash out between each treatment phase. The primary outcome measure was a sum score representing the adjusted total of the ratings of six components of a myoclonus rating scale in which stimulus sensitivity, motor impairment, functional disability, handwriting, and global assessments by investigators and patients were scored. Sequential clinical assessments were made by the same neurologist in the same environment at the same time of day.
RESULTS—Treatment with 24 g/day piracetam produced significant and clinically relevant improvement in the primary outcome measure of mean sum score (p=0.005) and in the means of its subtests of motor impairment (p=0.02), functional disability (p=0.003), and in global assessments by both investigator (p=0.002) and patient (p=0.01). Significant improvement in functional disability was also found with daily doses of 9.6 g and 16.8 g. The dose-effect relation was linear and significant. More patients showed clinically relevant improvement with the highest dosage and, in individual patients, increasing the dose improved response. Piracetam was well tolerated and adverse effects were few, mild, and transient.
CONCLUSIONS—This study provides further evidence that piracetam is an effective and safe medication in patients with Unverricht-Lundborg disease. In addition, it shows that a dose of 24 g is highly beneficial, more effective than lower doses and that a dose-effect relation exists. There is considerable variation in optimal individual dosage.



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Selected References

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  1. AIGNER B. R., MULDER D. W. Myoclonus. Clinical significance and an approach to classification. Arch Neurol. 1960 Jun;2:600–615. doi: 10.1001/archneur.1960.03840120006002. [DOI] [PubMed] [Google Scholar]
  2. Bente D., Glatthaar G., Ulrich G., Lewinsky M. Piracetam und Vigilanz. Elektroenzephalographische und klinische Ergebnisse einer Langzeitmedikation bei gerontopsychiatrischen Patienten. Arzneimittelforschung. 1978;28(9):1529–1530. [PubMed] [Google Scholar]
  3. Berkovic S. F., Andermann F., Carpenter S., Wolfe L. S. Progressive myoclonus epilepsies: specific causes and diagnosis. N Engl J Med. 1986 Jul 31;315(5):296–305. doi: 10.1056/NEJM198607313150506. [DOI] [PubMed] [Google Scholar]
  4. Bick R. L. In-vivo platelet inhibition by piracetam. Lancet. 1979 Oct 6;2(8145):752–753. doi: 10.1016/s0140-6736(79)90689-5. [DOI] [PubMed] [Google Scholar]
  5. Brown P., Steiger M. J., Thompson P. D., Rothwell J. C., Day B. L., Salama M., Waegemans T., Marsden C. D. Effectiveness of piracetam in cortical myoclonus. Mov Disord. 1993;8(1):63–68. doi: 10.1002/mds.870080112. [DOI] [PubMed] [Google Scholar]
  6. Croisile B., Trillet M., Fondarai J., Laurent B., Mauguière F., Billardon M. Long-term and high-dose piracetam treatment of Alzheimer's disease. Neurology. 1993 Feb;43(2):301–305. doi: 10.1212/wnl.43.2.301. [DOI] [PubMed] [Google Scholar]
  7. Eldridge R., Iivanainen M., Stern R., Koerber T., Wilder B. J. "Baltic" myoclonus epilepsy: hereditary disorder of childhood made worse by phenytoin. Lancet. 1983 Oct 8;2(8354):838–842. doi: 10.1016/s0140-6736(83)90749-3. [DOI] [PubMed] [Google Scholar]
  8. Fahn S. Newer drugs for posthypoxic action myoclonus: observations from a well-studied case. Adv Neurol. 1986;43:197–199. [PubMed] [Google Scholar]
  9. Fahn S. Posthypoxic action myoclonus: review of the literature and report of two new cases with response to valproate and estrogen. Adv Neurol. 1979;26:49–84. [PubMed] [Google Scholar]
  10. Goldberb M. A., Dorman J. D. Intention myoclonus: successful treatment with clonazepam. Neurology. 1976 Jan;26(1):24–26. doi: 10.1212/wnl.26.1.24. [DOI] [PubMed] [Google Scholar]
  11. Iivanainen M., Himberg J. J. Valproate and clonazepam in the treatment of severe progressive myoclonus epilepsy. Arch Neurol. 1982 Apr;39(4):236–238. doi: 10.1001/archneur.1982.00510160042008. [DOI] [PubMed] [Google Scholar]
  12. Israel L., Melac M., Milinkevitch D., Dubos G. Drug therapy and memory training programs: a double-blind randomized trial of general practice patients with age-associated memory impairment. Int Psychogeriatr. 1994 Fall;6(2):155–170. doi: 10.1017/s1041610294001729. [DOI] [PubMed] [Google Scholar]
  13. Koskiniemi M., Donner M., Majuri H., Haltia M., Norio R. Progressive myoclonus epilepsy. A clinical and histopathological study. Acta Neurol Scand. 1974;50(3):307–332. [PubMed] [Google Scholar]
  14. Lehesjoki A. E., Eldridge R., Eldridge J., Wilder B. J., de la Chapelle A. Progressive myoclonus epilepsy of Unverricht-Lundborg type: a clinical and molecular genetic study of a family from the United States with four affected sibs. Neurology. 1993 Nov;43(11):2384–2386. doi: 10.1212/wnl.43.11.2384. [DOI] [PubMed] [Google Scholar]
  15. Lehesjoki A. E., Koskiniemi M., Pandolfo M., Antonelli A., Kyllerman M., Wahlström J., Nergårdh A., Burmeister M., Sistonen P., Norio R. Linkage studies in progressive myoclonus epilepsy: Unverricht-Lundborg and Lafora's diseases. Neurology. 1992 Aug;42(8):1545–1550. doi: 10.1212/wnl.42.8.1545. [DOI] [PubMed] [Google Scholar]
  16. Levinson H. N. Dramatic favorable responses of children with learning disabilities or dyslexia and attention deficit disorder to antimotion sickness medications: four case reports. Percept Mot Skills. 1991 Dec;73(3 Pt 1):723–738. doi: 10.2466/pms.1991.73.3.723. [DOI] [PubMed] [Google Scholar]
  17. Malafosse A., Lehesjoki A. E., Genton P., Labauge P., Durand G., Tassinari C. A., Dravet C., Michelucci R., de la Chapelle A. Identical genetic locus for Baltic and Mediterranean myoclonus. Lancet. 1992 May 2;339(8801):1080–1081. doi: 10.1016/0140-6736(92)90667-r. [DOI] [PubMed] [Google Scholar]
  18. Meador K. J., Loring D. W., Huh K., Gallagher B. B., King D. W. Comparative cognitive effects of anticonvulsants. Neurology. 1990 Mar;40(3 Pt 1):391–394. doi: 10.1212/wnl.40.3_part_1.391. [DOI] [PubMed] [Google Scholar]
  19. Müller W. E., Koch S., Scheuer K., Rostock A., Bartsch R. Effects of piracetam on membrane fluidity in the aged mouse, rat, and human brain. Biochem Pharmacol. 1997 Jan 24;53(2):135–140. doi: 10.1016/s0006-2952(96)00463-7. [DOI] [PubMed] [Google Scholar]
  20. Norio R., Koskiniemi M. Progressive myoclonus epilepsy: genetic and nosological aspects with special reference to 107 Finnish patients. Clin Genet. 1979 May;15(5):382–398. doi: 10.1111/j.1399-0004.1979.tb01770.x. [DOI] [PubMed] [Google Scholar]
  21. Obeso J. A., Artieda J., Quinn N., Rothwell J. C., Luquin M. R., Vaamonde J., Marsden C. D. Piracetam in the treatment of different types of myoclonus. Clin Neuropharmacol. 1988 Dec;11(6):529–536. doi: 10.1097/00002826-198812000-00006. [DOI] [PubMed] [Google Scholar]
  22. Pennacchio L. A., Lehesjoki A. E., Stone N. E., Willour V. L., Virtaneva K., Miao J., D'Amato E., Ramirez L., Faham M., Koskiniemi M. Mutations in the gene encoding cystatin B in progressive myoclonus epilepsy (EPM1) Science. 1996 Mar 22;271(5256):1731–1734. doi: 10.1126/science.271.5256.1731. [DOI] [PubMed] [Google Scholar]
  23. Peuvot J., Schanck A., Deleers M., Brasseur R. Piracetam-induced changes to membrane physical properties. A combined approach by 31P nuclear magnetic resonance and conformational analysis. Biochem Pharmacol. 1995 Oct 12;50(8):1129–1134. doi: 10.1016/0006-2952(95)00225-o. [DOI] [PubMed] [Google Scholar]
  24. Truong D. D., Fahn S. Therapeutic trial with glycine in myoclonus. Mov Disord. 1988;3(3):222–232. doi: 10.1002/mds.870030306. [DOI] [PubMed] [Google Scholar]
  25. VAN HEYCOPTENHAMM, DE JAGER H. PROGRESSIVE MYOCLONUS EPILEPSY WITH LAFORA BODIES. CLINICAL-PATHOLOGICAL FEATURES. Epilepsia. 1963 Jun;4:95–119. doi: 10.1111/j.1528-1157.1963.tb05214.x. [DOI] [PubMed] [Google Scholar]
  26. Wilsher C. R., Bennett D., Chase C. H., Conners C. K., DiIanni M., Feagans L., Hanvik L. J., Helfgott E., Koplewicz H., Overby P. Piracetam and dyslexia: effects on reading tests. J Clin Psychopharmacol. 1987 Aug;7(4):230–237. [PubMed] [Google Scholar]

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