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Pharmacological predictors of heart rate and conductivity disorders in juvenile myoclonic epilepsy

https://doi.org/10.17749/2077-8333/epi.par.con.2021.051

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Abstract

Juvenile myoclonic epilepsy (JME) is the most common form of genetic generalized epilepsy. Patients with JME are at risk of life-threatening heart rhythm and conduction disorders as well as sudden death syndrome due to several potential mechanisms: genetic, clinical, neuroanatomical, pharmacological, psychological, comorbid. This lecture reviews important elements of knowledge about the pharmacological predictors of cerebral-cardiac syndrome and sudden unexpected death in epilepsy. The arrhythmogenic potential of antiepileptic drugs most often used in JME (valproic acid, levetiracetam, lamotrigine, topiramate and zonisamide) is considered, none of which can be classified as class A (drug without risk of QT interval prolongation or TdP) regarding a risk of QT interval prolongation and cardiac arrhythmias. Patients with JME require dynamic video-electroencephalographic monitoring and 24-hour electrocardiographic monitoring to reduce a risk of life-threatening cardiac arrhythmias.

About the Authors

N. A. Shnayder
Krasnoyarsk State Medical University; Bekhterev National Medical Research Centre for Psychiatry and Neurology
Russian Federation

Natalia A. Shnayder – Dr. Med. Sc., Professor, Leading Researcher, Department of Personalized Psychiatry and Neurology, Bekhterev National Medical Research Centre for Psychiatry and Neurology; Leading Researcher, Center of Collective Usage “Molecular and Cellular Technologies”, Krasnoyarsk State Medical University

WoS ResearcherID: M-7084-2014; RSCI SPIN-code: 1952-304

1 Partizan Zheleznyak Str., Krasnoyarsk 660022

3 Bekhterev Str., Saint Petersburg 192019



M. M. Petrova
Krasnoyarsk State Medical University
Russian Federation

Marina M. Petrova – Dr. Med. Sc., Professor, Chief of Chair of  Outpatient Therapy and General Practice with the Course of Postgraduate Education

Scopus Author ID: 23987271200; WoS ResearcherID: L-5623-2014; RSCI SPIN-code: 5563-1009

1 Partizan Zheleznyak Str., Krasnoyarsk 660022



K. V. Petrov
Krasnoyarsk State Medical University
Russian Federation

Kirill V. Petrov – Resident Physician, Chair of Neurological Diseases with the Course of Postgraduate Education

RSCI SPIN-code: 5830-0594

1 Partizan Zheleznyak Str., Krasnoyarsk 660022



R. F. Nasyrova
Bekhterev National Medical Research Centre for Psychiatry and Neurology
Russian Federation

Regina F. Nasyrova – Dr. Med. Sc., Senior Researcher, Head of the Department of Personalized Psychiatry and Neurology

RSCI SPIN-code: 1952-3043

3 Bekhterev Str., Saint Petersburg 192019



References

1. Karlov V.A., Zolovkina V.S. Problems of juvenile myoclonic epilepsy. A view through the prism of time. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2017; 117 (9-2): 24–33 (in Russ.). https://doi.org/10.17116/jnevro20171179224-33.

2. Volkov I.V., Volkova O.K. Juvenile myoclonic epilepsy. Update. Epilepsia i paroksizmalʹnye sostoania / Epilepsy and Paroxysmal Conditions. 2020; 12 (1S): 41–9 (in Russ.). https://doi.org/10.17749/2077-8333.2020.12.1S.S41-S49.

3. Belousova E.D., Shkolnikova M.A. Sudden unexpected death in genetic epileptic encephalopathies: a role of neurocardiac genes. Epilepsia i paroksizmalʹnye sostoania / Epilepsy and Paroxysmal Conditions. 2018; 10 (3): 63–70 (in Russ.). https://doi.org/10.17749/2077-8333.2018.10.3.063-070.

4. You C.F., Chong C.F., Wang T.L., et al. Unrecognized paroxysmal ventricular standstill masquerading as epilepsy: a Stokes-Adams attack. Epileptic Disord. 2007; 9 (2): 179–81. https://doi.org/10.1684/epd.2007.0105.

5. Hunt J., Tang K. Long QT syndrome presenting as epileptic seizures in an adult. Emerg Med J. 2005; 22 (8): 600–1. https://doi.org/10.1136/emj.2003.007997.

6. Tan H.L., Hou C.J., Lauer M.R., Sung R.J. Electrophysiologic mechanism of the long QT interval syndromes and torsades de pointes. Ann Intern Med. 1995; 122 (9): 701–14. https://doi.org/10.7326/0003-4819-122-9-199505010-00009.

7. Chahal C.A., Salloum M.N., Alahdab F., et al. Systematic review of the genetics of sudden unexpected death in epilepsy: potential overlap with sudden cardiac death and arrhythmia-related genes. J Am Heart Assoc. 2020; 9 (1): e012264. https://doi.org/10.1161/JAHA.119.012264.

8. Donner E.J. Sudden unexpected death in epilepsy: who are the children at risk? Paediatr Child Health. 2014; 19 (7): 389. https://doi.org/10.1093/pch/19.7.389.

9. Scheffer I.E., Berkovic S., Capovilla G., et al. ILAE classification of the epilepsies: position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017; 58 (4): 512–21. https://doi.org/10.1111/epi.13709.

10. Shilkina O.S., Schnaider N.A. Epidemiology of juvenile myoclonic epilepsy. Neurology, Neuropsychiatry, Psychosomatics. 2017; 9 (1): 26–31 (in Russ.). https://doi.org/10.14412/2074-2711-2017-1S-26-31.

11. Shnayder N.A., Shilkina O.S., Petrov K.V., et al. Clinical and genetic heterogenity of juvenile myoclonic epilepsy. Epilepsia i paroksizmalʹnye sostoania / Epilepsy and Paroxysmal Conditions. 2016; 8 (2): 20–36 (in Russ.). https://doi.org/10.17749/2077-8333.2016.8.2.020-036.

12. Caciagli L., Wandschneider B., Xiao F., et al. Abnormal hippocampal structure and function in juvenile myoclonic epilepsy and unaffected siblings. Brain. 2019; 142 (9): 2670–87. https://doi.org/10.1093/brain/awz215.

13. Wandschneider B., Koepp M., Scott C., et al. Structural imaging biomarkers of sudden unexpected death in epilepsy. Brain. 2015; 138 (10): 2907–19. https://doi.org/10.1093/brain/awv233.

14. Moskaleva P.V., Shilkina O.S., Shnayder N.A. Individual neuropsychological characteristics in patients with juvenile myoclonic epilepsy. Psychology in Russia: State of the Art. 2018; 11 (2): 42–54. https://doi.org/10.11621/pir.2018.0204.

15. Sullivan J.E., Dlugos D.J. Idiopathic generalized epilepsy. Curr Treat Options Neurol. 2004; 6 (3): 231–42. https://doi.org/10.1007/s11940-004-0015-6.

16. Verrotti A., Cerminara C., Coppola G., et al. Levetiracetam in juvenile myoclonic epilepsy: long-term efficacy in newly diagnosed adolescents. Dev Med Child Neurol. 2008; 50 (1): 29–32. https://doi.org/10.1111/j.1469-8749.2007.02009.x.

17. Morris G.L., Hammer A.E., Kustra R.P., Messenheimer J.A. Lamotrigine for patients with juvenile myoclonic epilepsy following prior treatment with valproate: results of an open-label study. Epilepsy Behav. 2004; 5 (4): 509–12. https://doi.org/10.1016/j.yebeh.2004.04.002.

18. Shah R.R. Pharmacogenetic aspects of drug-induced torsade de pointes: potential tool for improving clinical drug development and prescribing. Drug Safety. 2004; 27 (3): 145–72. https://doi.org/10.2165/00002018-200427030-00001.

19. Shah R.R. Cardiac effects of antiepileptic drugs. In: Panayiotopoulos C.P. (Ed.) Atlas of epilepsies. London: Springer; 2010: 1479–86. https://doi.org/10.1007/978-1-84882-128-6_221.

20. Mladěnka P., Applová L., Patočka J., et al. Comprehensive review of cardiovascular toxicity of drugs and related agents. Med Res Rev. 2018; 38 (4): 1332–403. https://doi.org/10.1002/med.21476.

21. Jordan J., Astrup A., Engeli S., et al. Cardiovascular effects of phentermine and topiramate: a new drug combination for the treatment of obesity. J Hypertens. 2014; 32 (6): 1178–88. https://doi.org/10.1097/HJH.0000000000000145.

22. Ishizue N., Niwano S., Saito M., et al. Polytherapy with sodium channel-blocking antiepileptic drugs is associated with arrhythmogenic ST-T abnormality in patients with epilepsy. Seizure. 2016; 40: 81–7. https://doi.org/10.1016/j.seizure.2016.06.004.

23. Bourin M. Mechanism of action of valproic acid and its derivatives. SOJ Pharm Sci. 2020; 7 (1): 1–4. https://doi.org/10.15226/2374-6866/7/1/001994.

24. Amin O.S., Mahmood A. Valproic acid: does it have an antiarrhythmic action? Cukurova Med J. 2013; 38: 592–600.

25. Aslan K., Deniz A., Demir T., et al. Is cardiac repolarization time different between epilepsy patients on antiepileptic drugs and healthy subjects? Epilepsi. 2018; 24 (1): 15–20. https://doi.org/10.14744/epilepsi.2017.29863.

26. Asoğlu R., Özdemir M., Aladağ N., Asoğlu E. Evaluation of cardiac repolarization indices in epilepsy patients treated with carbamazepine and valproic acid. Medicina (Kaunas). 2020; 56 (1): 20. https://doi.org/10.3390/medicina56010020.

27. Cataldi M., Lariccia V., Secondo A., et al. The antiepileptic drug levetiracetam decreases the inositol 1,4,5-trisphosphate-dependent [Ca2+]I increase induced by ATP and bradykinin in PC12 cells. J Pharmacol Exp Ther. 2005; 313 (2): 720–30. https://doi.org/10.1124/jpet.104.079327.

28. Niespodziany I., Klitgaard H., Margineanu D.G. Levetiracetam inhibits the high-voltage-activated Ca(2+) current in pyramidal neurones of rat hippocampal slices. Neurosci Lett. 2001; 306: 5–8. https://doi.org/10.1016/s0304-3940(01)01884-5.

29. Pisani A., Bonsi P., Martella G., et al. Intracellular calcium increase in epileptiform activity: modulation by levetiracetam and lamotrigine. Epilepsia. 2004; 45 (7): 719–28. https://doi.org/10.1111/j.0013-9580.2004.02204.x.

30. Deshpande L.S., Delorenzo R.J. Mechanisms of levetiracetam in the control of status epilepticus and epilepsy. Front Neurol. 2014; 5: 11. https://doi.org/10.3389/fneur.2014.00011.

31. Tong X., Patsalos P.N. A microdialysis study of the novel antiepileptic drug levetiracetam: extracellular pharmacokinetics and effect on taurine in rat brain. Br J Pharmacol. 2001; 133 (6): 867–74. https://doi.org/10.1038/sj.bjp.0704141.

32. Madeja M., Margineanu D.G., Gorji A., et al. Reduction of voltageoperated potassium currents by levetiracetam: a novel antiepileptic mechanism of action? Neuropharmacology. 2003; 45 (5): 661–71. https://doi.org/10.1016/s0028-3908(03)00248-x.

33. Surges R., Volynski K.E., Walker M.C. Is levetiracetam different from other antiepileptic drugs? Levetiracetam and its cellular mechanism of action in epilepsy revisited. Ther Adv Neurol Disord. 2008; 1 (1): 13–24. https://doi.org/10.1177/1756285608094212.

34. Hulhoven R., Rosillon D., Bridson W.E., et al. Effect of levetiracetam on cardiac repolarization in healthy subjects: a single-dose, randomized, placebo- and active-controlled, four-way crossover study. Clin Ther. 2008; 30 (2): 260–70. https://doi.org/10.1016/j.clinthera.2008.02.002.

35. Altun Y., Yasar E. Effects of valproate, carbamazepine and levetiracetam on Tp-e interval, Tp-e/QT and Tp-e/QTc ratio. Ideggyogy Sz. 2020; 73 (3–4): 121–7. https://doi.org/10.18071/isz.73.0121.

36. Siniscalchi A., Scaglione F., Sanzaro E., et al. Effects of phenobarbital and levetiracetam on PR and QTc intervals in patients with post-stroke seizure. Clin Drug Investig. 2014; 34 (12): 879–86. https://doi.org/10.1007/s40261-014-0243-9.

37. Page C.B., Mostafa A., Saiao A., et al. Cardiovascular toxicity with levetiracetam overdose. Clin Toxicol (Phila). 2016; 54 (2): 152–4. https://doi.org/10.3109/15563650.2015.1115054.

38. Brodde O.E., Michel M.C. Adrenergic and muscarinic receptors in the human heart. Pharmacol Rev. 1999; 51 (4): 651–90.

39. Yasam V.R., Jakki S.L., Senthil V., et al. A pharmacological overview of lamotrigine for the treatment of epilepsy. Exp Rev Clin Pharmacol. 2016; 9 (12): 1533–46. https://doi.org/10.1080/17512433.2016.1254041.

40. Rodrigues R., Amador P., Rassi L., et al. Brugada pattern in a patient medicated with lamotrigine. Rev Port Cardiol. 2013; 32 (10): 807–10. https://doi.org/10.1016/j.repc.2013.01.009.

41. Danielsson B.R., Lansdell K., Patmore L., Tomson T. Effects of the antiepileptic drugs lamotrigine, topiramate and gabapentin on hERG potassium currents. Epilepsy Res. 2005; 63 (1): 17–25. https://doi.org/10.1016/j.eplepsyres.2004.10.002.

42. French L.K., McKeown N.J., Hendrickson R.G. Complete heart block and death following lamotrigine overdose. Clin Toxicol (Phila). 2011; 49 (4): 330–3. https://doi.org/10.3109/15563650.2011.572555.

43. Nogar J.N., Minns A.B., Savaser D.J., Ly B.T. Severe sodium channel blockade and cardiovascular collapse due to a massive lamotrigine overdose. Clin Toxicol (Phila). 2011; 49 (9): 854–7. https://doi.org/10.3109/15563650.2011.617307.

44. Mestre M., Djellas Y., Carriot T., Cavero I. Frequency-independent blockade of cardiac Na+ channels by riluzole: comparison with established anticonvulsants and class I anti-arrhythmics. Fundam Clin Pharmacol. 2000; 14: 107–17. https://doi.org/10.1111/j.1472-8206.2000.tb00398.x.

45. Leong K.M., Seligman H., Varnava A.M. Proarrhythmogenic effects of lamotrigine during ajmaline testing for Brugada syndrome. Heart Rhythm Case Rep. 2017; 3 (3): 167–71. https://doi.org/10.1016/j.hrcr.2016.11.006.

46. Strimel W.J., Woodruff A., Cheung P., et al. Brugada-like electrocardiographic pattern induced by lamotrigine toxicity. Clin Neuropharmacol. 2010; 33 (5): 265–7. https://doi.org/10.1097/WNF.0b013e3181e8ac66.

47. Parisi P., Oliva A., Vidal M.C., et al. Coexistence of epilepsy and Brugada syndrome in a family with SCN5A mutation. Epilepsy Res. 2013; 105 (3): 415–8. https://doi.org/10.1016/j.eplepsyres.2013.02.024.

48. Aurlien D., Taubøll E., Gjerstad L. Lamotrigine in idiopathic epilepsy – increased risk of cardiac death? Acta Neurol Scand. 2007; 115 (3): 199–203. https://doi.org/10.1111/j.1600-0404.2006.00730.x.

49. VanLandingham K.E., Dixon R.M. Lamotrigine in idiopathic epilepsy – increased risk of cardiac death. Acta Neurol Scand. 2007; 116 (5): 345. https://doi.org/10.1111/j.1600-0404.2007.00903.x.

50. Sanguinetti M.C., Tristani-Firouzi M. hERG potassium channels and cardiac arrhythmia. Nature. 2006; 440 (7083): 463–9. https://doi.org/10.1038/nature04710.

51. VI-0521 (QNEXA®) Advisory Committee Briefing Document. Endocrinologic and Metabolic Drugs Advisory Committee Meeting. NDA 022580. Available at: https://www.nutricity.it/wp-content/uploads/2013/02/Fentermina-Topiramato.pdf (accessed 28.04.2021).

52. Jovanovi M., Sokić D., Grabnar I., et al. Effect of long-term topiramate therapy on serum bicarbonate and potassium levels in adult epileptic patients. Ann Pharmacother. 2014; 48 (8): 992–7. https://doi.org/10.1177/1060028014534397.

53. Nadkarni G.N., Annapureddy N., Meisels I.S. Topiramate-induced refractory hypokalemia. Am J Ther. 2014; 21 (5): e157–8. https://doi.org/10.1097/MJT.0b013e3182691cf5.

54. Yousaf A. A rare cause of iatrogenic sinus bradycardia. J Case Rep. 2016; 6: 90–3. https://doi.org/10.17659/01.2016.0022.

55. Naranjo C., Shear N., Lanctôt K. Advances in the diagnosis of adverse drug reactions. J Clin Pharmacol. 1992; 32 (10): 897–904. https://doi.org/10.1002/j.1552-4604.1992.tb04635.x.

56. Porter R.J., Dhir A., Macdonald R.L., Rogawski M.A. Mechanisms of action of antiseizure drugs. Handb Clin Neurol. 2012; 108: 663–81. https://doi.org/10.1016/B978-0-444-52899-5.00021-6.

57. Meldrum B., Rogawski M. Molecular targets for antiepileptic drug development. Neurotherapeutics. 2007; 4 (1): 18–61. https://doi.org/10.1016/j.nurt.2006.11.010.

58. Kothare S.V., Valencia I., Khurana D.S., et al. Efficacy and tolerability of zonisamide in juvenile myoclonic epilepsy. Epileptic Disord. 2004; 6 (4): 267–70.

59. Hofer K.E., Trachsel C., Rauber-Lüthy C., et al. Moderate toxic effects following acute zonisamide overdose. Epilepsy Behav. 2011; 21 (1): 91–3. https://doi.org/10.1016/j.yebeh.2011.02.023.

60. Galtrey C.M., Levee V., Arevalo J., Wren D. Long QT syndrome masquerading as epilepsy. Pract Neurol. 2019; 19 (1): 56–61. https://doi.org/10.1136/practneurol-2018-001959.

61. Auerbach D.S., Biton Y., Polonsky B., et al. Risk of cardiac events in long QT syndrome patients when taking antiseizure medications. Transl Res. 2018; 191: 81–92e7. https://doi.org/10.1016/j.trsl.2017.10.002.

62. Johnson J.N., Hofman N., Haglund C.M., et al. Identification of a possible pathogenic link between congenital long QT syndrome and epilepsy. Neurology. 2009; 72: 224– 31. https://doi.org/10.1212/01.wnl.0000335760.02995.ca.

63. Omichi C., Momose Y., Kitahara S. Congenital long QT syndrome presenting with a history of epilepsy: misdiagnosis or relationship between channelopathies of the heart and brain? Epilepsia. 2010; 51 (2): 289–92. https://doi.org/10.1111/j.1528-1167.2009.02267.x.

64. Potential QTc-Prolonging Agents. Available at: https://go.drugbank.com/categories/DBCAT002691 (accessed 28.04.2021).

65. International Conference on Harmonisation; guidance on E14 Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs; availability. Notice. Fed Regist. 2005; 70 (202): 61134–5.

66. Fanoe S., Kristensen D., Fink-Jensen A., et al. Risk of arrhythmia induced by psychotropic medications: a proposal for clinical management. Eur Heart J. 2014; 35 (20): 1306–15. https://doi.org/10.1093/eurheartj/ehu100.

67. Hoffmann P., Warner B. Are hERG channel inhibition and QT interval prolongation all there is in drug-induced torsadogenesis? A review of emerging trends. J Pharmacol Toxicol Methods. 2006; 53: 87–105. https://doi.org/10.1016/j.vascn.2005.07.003.

68. Roden D.M. Drug-induced prolongation of the QT interval. N Engl J Med. 2004; 350 (10): 1013–22. https://doi.org/10.1056/NEJMra032426.

69. Shah R.R. Drug-induced QT interval prolongation: regulatory perspectives and drug development. Ann Med. 2004; 36 (1): 47–52. https://doi.org/10.1080/17431380410032445.

70. Nogawa H., Kawai T. hERG trafficking inhibition in drug-induced lethal cardiac arrhythmia. Eur J Pharmacol. 2014; 741: 336–9. https://doi.org/10.1016/j.ejphar.2014.06.044.

71. Jansen K., Lagae L. Cardiac changes in epilepsy. Seizure. 2010; 19 (8): 455–60. https://doi.org/10.1016/j.seizure.2010.07.008.

72. Van der Lende M., Surges R., Sander J.W., Thijs R.D. Cardiac arrhythmias during or after epileptic seizures. J Neurol Neurosurg Psychiatry. 2016; 87 (1): 69–74. https://doi.org/10.1136/jnnp-2015-310559.

73. Tomson T., Kennebäck G. Arrhythmia, heart rate variability, and antiepileptic drugs. Epilepsia. 1997; 38 (11): S48–51. https://doi.org/10.1111/j.1528-1157.1997.tb06128.x.

74. Sarycheva T., Lavikainen P., Taipale H., et al. Antiepileptic drug use and mortality among community-dwelling persons with Alzheimer disease. Neurology. 2020; 94 (20): e2099–108. https://doi.org/10.1212/WNL.0000000000009435.


For citation:


Shnayder N.A., Petrova M.M., Petrov K.V., Nasyrova R.F. Pharmacological predictors of heart rate and conductivity disorders in juvenile myoclonic epilepsy. Epilepsy and paroxysmal conditions. 2021;13(2):168-179. (In Russ.) https://doi.org/10.17749/2077-8333/epi.par.con.2021.051

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