TRANSFORMATION OF THE EPILEPTIC SYSTEM. CURRENT STATUS OF THE PROBLEM AND POSSIBLE WAYS TO SOLVE IT
Abstract
We have conducted an experiment with valproic acid drugs (used as an example), where we have identified the determinant and dominant structures of the epileptic system. The main determinant structure is hypothalamus; it is responsible for secondary generalized seizures formation. The next strusctures in the hierarchy are contralateral and ipsilateral hippocampus, contralateral cortex. Collateral subordination of the structures and the transformation of the epileptic pathological system has been revealed. We demonstrated the advantages of the Depakin Chronosphere microgranules and effectiveness of the drug for treating children, adolescents, adults and elderly patients with epilepsy. The results of experimental studies with Nano-Phenazepam substantiate its further development as an antiepileptic drug for the treatment of secondary generalized seizures and prevention of status epilepticus. To optimize the surgical treatment of pharmacoresistant epilepsies, it is necessary to use minimally invasive functional neurosurgical techniques and/or their combination in each individual patient.
About the Authors
G. N. Avakyan
Russian National Research Medical University named after N.I. Pirogov, Health Ministry of Russian Federation
Russian Federation
Russian Federation
MD, PhD, Honored Scientist of Russia, Professor at the Department of Neurology, Neurosurgery
and Medical Genetics, Russian National Research Medical University named after N.I. Pirogov, Health Ministry of Russian Federation
Address: ul. Ostrovityanova, 1, Moscow, Russia, 117997
G. G. Avakyan
Russian National Research Medical University named after N.I. Pirogov, Health Ministry of Russian Federation
Russian Federation
Russian Federation
MD, associate professor at the Department of Neurology, Neurosurgery and Medical Genetics, Russian National Research Medical University named after N.I. Pirogov, Health Ministry of Russian Federation
Address: ul. Ostrovityanova, 1, Moscow, 117997, Russia. Tel.: +7(495)5316941
References
1. Guekht A., Hauser W. A., Milchakova L., Churillin Y., Shpak A., Gusev E. The epidemiology of epilepsy in the Russian Federation. Epilepsy Res. 2010; 92 (2-3): 209-18.
2. Forsgren L., Beghi E., Oun A., Sillanpaa M. The epidemiology of epilepsy in Europe a systematic review. Eur J Neurol. 2005; 12 (4): 245-53.
3. Recommendations of the Expert Council of the Russian League against epilepsy. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2011; 5 (2): 23-25 (in Russian).
4. Brodie M. J., Shorvon D., Johannessen S., Halasz P., Reynolds A., Wieser H. G., Wolf P. European standards of care in epilepsy. Communication from the Commission of the International League against epilepsy (ILAE). www.neuronet.ru. Accessed: 16.10.2016.
5. Gekht A. B., Avakyan G. N., Gusev E. I. Current standards in the diagnosis and treatment of epilepsy. Zhurnal nevrologiya i psikhiatriya. 2009; 99 (7): 4-7 (in Russian).
6. Karceski S., Morrell M. J., Carpenter D. Treatment of epilepsy in adults: expert opinion. Epilepsy & Behavior. 2005; 7: 1-64.
7. Zenkov L. R. Place of valproates (Depakine) in the pharmacotherapy of epilepsy in the 21st century. Russkii meditsinskii zhurnal. 2009; 11: 726-732 (in Russian).
8. Nakken K. O., Eriksson A. S., Kwan P., Brodie M. J. Combination Therapy in Epilepsy. When and What to Use. Drugs. 2006; 66 (14): 1817-1829.
9. Trinka E., et al. Efficacy and Safety of Intravenous Valproate for Status Epilepticus: A Systematic Review. CNS Drugs. 2014.
10. Verrotti A., et al. Acta Neurol. 2011; 4: 5-9.
11. Motte J., Pedespan J. M., Sevestre M., et al. Acceptability and tolerance of sodium valproate, a new sustained-action granule formulation, in monotherapy for epileptic children from 3 years old. Arch Pediatr. 2005; 12 (10): 1533-1539.
12. Dulac O., Alvarez J. C. Pharmacotherapy. 2005; 25 (1): 35-4.
13. Belousova E. D., Avakyan G. N. Efficacy and safety of prolonged sodium valproate (Depakine® Chronosphere) as a first-choice drug for treatment of epilepsy in adults. Nevrologiya, neiropsikhiatriya, psikhosomatika. 2012; 4 (2): 48-54 (in Russian).
14. The resolution of the meeting of the working group of the Russian League against epilepsy. Epilepsiya i paroksizmal’nye sostoyaniya. 2016; 8 (4): 109-111 (in Russian).
15. Belousova E. D., Ermakov A. Yu. The use of Depakine Chronosphere as a first- line monotherapy for children with epilepsy. Nevrologiya, neiropsikhiatriya, psikhosomatika. 2010; 3: 52-57 (in Russian).
16. Avakyan G. N., Belousova E. D., Ermakov A. Yu., Avakyan G. G. Depakine Chronosphere – a novel drug for treatment of epilepsy in children, adolescents, adults and elderly people. Experience of use in Russian clinical practice. Experience of use in Russia. Epilepsiya i paroksizmal’nye sostoyaniya. 2013; 5 (3): 41-48 (in Russian).
17. Kwan P., et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia. 2010; 51: 1069-77.
18. Cram L., Dulac O., Frey H. Commission on antiepileptic drags of the International League Against Epilepsy Guidelines for antiepileptic drug trials in children. 1994; 18.
19. Kryzhanovskiy G. N. Determinantal structures in pathology of the nervous system. Determinantnye struktury v patologii nervnoi sistemy. Moscow. 1980: 359 s (in Russian).
20. Karlov V. A. Epilepsy. Epilepsiya. M. 1990.
21. Holmes M. D. Epilepsy. Epilepsia. 2008; 49: 3-14.
22. Spenser D. D.P., Kotagal H. O. (eds). The Epilepsies: Etiologicy and Prevention. San Diego etc. 1999: 259-264.
23. Karlov V. A. Epilepsy in children and adult women and men. A guide for physicians. Epilepsiya u detei i vzroslykh, zhenshchin i detei. Rukovodstvo dlya vrachei. Moscow. 2010; 718 s (in Russian).
24. Karlov V. A., Gnezditskiy V. V. Absence epilepsy in children and adults [Absansnaya epilepsiya u detei i vzroslykh (in Russian)]. Moscow. 2005.
25. Karlov V. A. Zhurn. nevrol. i psikhiatr. 2005; 3: 55-60.
26. Bekhtereva N. P., Kambarova D. K., Pozdeev V. K. Sustainable pathological condition in the diseases of the brain [Ustoichivoe patologicheskoe sostoyanie pri boleznyakh mozga (in Russian)]. D. 1978.
27. Voronina T. A., Nerobkova L. N. Methodical instructions to study the anticonvulsant activity of pharmacological substances. Manual on experimental (preclinical) study of new pharmacological substances [Metodicheskie ukazaniya po izucheniyu protivosudorozhnoi aktivnosti farmakologicheskikh veshchestv. Rukovodstvo po eksperimental’nomu (doklinicheskomu) izucheniyu novykh farmakologicheskikh veshchestv (in Russian)]. Moscow. 2005; 277-294.
28. Walton N. Y., Treiman D. M., Lamotrigine vs. phenytoin for treatment of status epilepticus: comparison in an experimental model. Epilepsy Res. 1996; 24: 19-28.
29. Avakyan G. G. Clinical and neurophysiological study of combinations of new forms of anticonvulsants and antioxidants in patients with epilepsy with secondary generalized seizures. PhD diss. [Kliniko-neirofiziologicheskoe izuchenie kombinatsii novykh form antikonvul’santov i antioksidanta u bol’nykh epilepsiei s vtorichno- generalizovannymi pristupami. Dis. …kand. med. nauk. (in Russian)]. Moscow. 2011; 156 s.
30. Stoiko M. I. The use of sodium valproate, antioxidant Mexidol and their combinations for the treatment and prevention of secondary generalized seizures in epilepsy (clinical-experimental study). PhD diss. [Izuchenie vozmozhnosti primeneniya val’proata natriya, antioksidanta meksidola i ikh kombinatsii dlya lecheniya i profilaktiki vtorichno-generalizovannykh pripadkov pri epilepsii (kliniko-eksperimental’noe issledovanie). Dis. …kand. med. nauk. (in Russian)]. Moscow. 2001.
31. Avakyan G. N., Badalyan O. L., Burd S. G., Val’dman E. A., Voronina T. A., Nerobkova L. N., Krikova E. V., Avakyan G. G., Chukanova A. S., Stoiko M. I., Savenkov A. A. Experimental and clinical epileptology Epilepsiya i paroksizmal’nye sostoyaniya / Epilepsy and paroxysmal conditions. 2010; 2 (4): 41-53.
32. Voronina T. A., Nerobkova L. N., Avakyan G. N., Khromykh E. A., Gaidukov I. O., Avakyan G. G. Search for new antiepileptic drugs on the basis of the conception of epileptic system formation. Epilepsiya i paroksizmal’nye sostoyaniya / Epilepsy and paroxysmal conditions. 2013; 5 (4): 29-32.
33. Alyautdin R. N., Kreuter J., Kharkevich D. A. Interaction of poly(butyl)cyanoacrilate nanoparticles with blood-brain barrier in vivo and in vitro. J. Drug Target. 2001; 9: 209-221.
34. Razzhivina V. A. Investigation of phenazepam effects on poly(butyl)cyanoacrylate nanoparticles. MD diss. [Izuchenie effektov fenazepama na poli(butil)tsianokrilatnykh nanochastitsakh. Avtoref. diss. …dokt. med. nauk (in Russian)]. Moscow. 2009; 24 s.
35. Sperling M. R. Evolution of surgical treatment of epilepsy. International conference [Evolyutsiya khirurgicheskogo lecheniya epilepsii. Mezhdunarodnaya konferentsiya (in Russian)] Moscow. M. 2016; Chapter 5.9: 439-450.
Review
For citations:
Avakyan G.N., Avakyan G.G. TRANSFORMATION OF THE EPILEPTIC SYSTEM. CURRENT STATUS OF THE PROBLEM AND POSSIBLE WAYS TO SOLVE IT. Epilepsy and paroxysmal conditions. 2017;9(2):6-19. (In Russ.) https://doi.org/10.17749/2077-8333.2017.9.2.006-019
Views: 603
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Email this article 
