Применение препарата ботулинического токсина типа А (Ботокс) в лечении детского церебрального паралича

При детском церебральном параличе (ДЦП) препараты ботулинического токсина типа А (БТА) применяются более 20 лет. Несмотря на это сегодня отсутствует унифицированный протокол проведения инъекций препаратов БТА и расчета доз при ДЦП. Для правильного выбора мышц-мишеней для ботулинотерапии большое значение имеют опыт врача, детальный анализ неврологического и ортопедического статуса пациента, применение стандартизированных функциональных шкал для оценки
двигательных возможностей ребенка. В статье представлен детальный обзор международных исследований по многоуровневому подходу к ботулинотерапии при ДЦП и рекомендаций по расчету доз. На основании результатов собственных наблюдений эффективности и безопасности инъекций препарата БТА Ботокс у детей с церебральным параличом представлены рекомендуемые диапазоны доз для мышц
нижних и верхних конечностей, использованные при однократных инъекциях, применение которых позволило достичь клинически значимого снижения спастичности без развития нежелательной слабости. Рассмотрены клинические примеры с разбором распределения дозы препарата Ботокс по мышцам-мишеням и расчетом общей дозы препарата. Представленные диапазоны доз препарата Ботокс носят исключительно рекомендательный характер.

1. Koman L.A., Mooney J.F. 3rd, Smith B. et al. Management of cerebral palsy with botulinum-A toxin: preliminary investigation. J Pediatr Orthop 1993;13(4):489–95.

2. Graham H.K., Aoki K.R., Autti-Ramo I. et al. Recommendations for the use of botulinum toxin type A in the management of cerebral palsy. Gait Posture 2000;11: 67–79.

3. Heinen F., Molenaers G., Fairhurst C. et al. European consensus table 2006 on botulinum toxin for children with cerebral palsy. Eur J Paediatr Neurol 2006;10(5–6):215–25.

4. Heinen F., Desloovere K., Schroeder A.S. et al. The updated European Consensus 2009 on the use of Botulinum toxin for children with cerebral palsy. Eur J Paediatr Neurol 2010;14(1):45–66.

5. Love S.C., Novak I., Kentish M. et al. Botulinum toxin assessment, intervention and after-care for lower limb spasticity in children with cerebral palsy: international consensus statement. Eur J Neur 2010;17(Suppl 2):9–37.

6. Bax M., Goldstein M., Rosenbaum P. et al. Proposed definition and classification of cerebral palsy. Dev Med Child Neurol 2005;47(8):571–6.

7. Miller F. Cerebral palsy. New York: Springer Science, 2005. 1055 p.

8. Батышева Т.Т., Быкова О.В., Виноградов А.В. Приверженность семьи к лечению ребенка с неврологической патологией. Журн неврол и психиатр им. С.С. Корсакова 2012;7(2): 56–63.

9. Семенова К.А., Махмудова Н.М. Медицинская реабилитация и социальная адаптация больных детским церебральным параличом. Ташкент: Медицина, 1979. 487 с.

10. Surveillance of cerebral palsy in Europe: a collaboration of cerebral palsy surveys and registers. Dev Med Child Neurol 2000;42(12):816–24.

11. Palisano R., Rosenbaum P., Walter S. et al. Development and reliability of a system to classify gross motor function in children with cerebral palsy. Dev Med Child Neurol1997;39(4):214–23.

12. Palisano R.J. A collaborative model of service delivery for children with movement disorders: a framework for evidence-based decision making. Phys Ther 2006;86(9): 1295–305.

13. Hanna S.E., Rosenbaum P.L., Bartlett D.J. et al. Stability and decline in gross motor function among children and youth with cerebral palsy aged 2 to 21 years. Dev Med Child Neurol 2009;51(4):295–302.

14. Eliasson A.C., Krumlinde-Sundholm L., Rösblad B. et al. The Manual Ability Classification System (MACS) for children with cerebral palsy: scale development and evidence of validity and reliability. Dev Med Child Neurol 2006;48(7):549–54.

15. Hidecker M.J., Paneth N., Rosenbaum P.L. et al. Developing and validating the Communication Function Classification System for individuals with cerebral palsy. Dev Med Child Neurol 2011;53(8):704–10.

16. Hidecker M.J., Ho N.T., Dodge N. et al. Inter-relationships of functional status in cerebral palsy: analyzing gross motor function, manual ability, and communication function classification systems in children. Dev Med Child Neurol 2012;54(8):737–42.

17. Bohannon R.W., Smith M.B. Interrater reliability of a modified Ashworth scale of muscle spasticity. Phys Ther 1987;67(2): 206–7.

18. Boyd R.N., Graham H.K. Objective measurement of clinical findings in the use of Botulinum toxin type A for the management of children with cerebral palsy. Eur J Neurol 1999;6(Suppl. 4):23–35.

19. Gage J.R., Stout J.L. Gait analysis: kinematics, kinetics, electromyography, oxygen consumption and pedobarography. In: The identification and treatment of gait problems in cerebral palsy (Eds. Gage J.R., Schwartz M.H., Koop S.E., Novacheck T.F.). London: Mac Keith Press, 2009. P. 260–284.

20. Leonard J., Graham H.K. Treatment of motor disorders in cerebral palsy with bo tulinum neurotoxin. In book: Botulinum toxin: Therapeutic clinical practice and science (Ed. by J. Jankovic). Philadelphia: Saunders Elsevier, 2009. P. 172–191.

21. Simpson D.M., Gracies J.M., Graham H.K. et al. Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Assessment: Botulinum neurotoxin for the treatment of spasticity (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2008;70(19):1691–8.

22. Delgado M.R., Hirtz D., Aisen M. et al. Practice parameter: pharmacologic treatment of spasticity in children and adolescents with cerebral palsy (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology 2010;74(4):336–43.

23. Hoare B.J., Wallen M.A., Imms C. et al. Botulinum toxin A as an adjunct to treatment in the management of the upper limb in children with spastic cerebral palsy (UPDATE). Cochrane Database Syst Rev 2010; (1):CD003469.

24. Sakzewski L., Ziviani J., Boyd R. Systematic review and meta-analysis of therapeutic management of upper-limb dysfunction in children with congenital hemiplegia. Pediatrics 2009;123(6):1111–22.

25. Артеменко А.Р., Куренков А.Л. Ботулинический токсин: вчера, сегодня, завтра. Нервно-мышечные болезни 2013;2:6–18.

26. Dressler D. Clinical applications of botulinum toxin. Curr Opin Microbiol 2012;15(3):325–36.

27. Burgen A., Dickens F., Zatman L.J. The action of botulinum toxin on the neuromusculat junction. J Phisiol 1949;109:10–24.

28. Grissom J.R. Chemical denervation. In book: Electrodiagnostic medicine, 2nd edition (Eds. D. Dumitru, M.J. Zwarts, A.A. Amato). Philadelphia: Hanley & Belfus, Inc., 2002. P. 479–512.

29. Куренков А.Л., Артеменко А.Р., Никитин С.С., Орлова О.Р. Современные представления о механизмах действия ботулинического токсина типа А. Врач 2009;7:8–12.

30. Giladi N. The mechanism of action of botulinum toxin type A in focal dystonia is most probably through its dual effect on efferent (motor) and afferent pathways at the injected site. J Neurol Sci 1997;152: 132–5.

31. Dressler D., Saberi F.A., Barbosa E.R. Botulinum toxin: mechanisms of action. Arq Neuropsiquiatr 2005;63:180–5.

32. Aoki K.R. Evidence for antinociceptive activity of botulinum toxin type A in pain management. Headache 2003;43 (Suppl. 1): 9–15.

33. Aoki K.R. Review of a proposed mechanism for the antinociceptive action of botulinum toxin type A. Neurotoxicology 2005;26 (5):785–93.

34. Durham P.L., Cady R. Insights into the mechanism of onabotulinumtoxinA in chronic migraine. Headache 2011;51 (10):1573–7.

35. Gazerani P., Pedersen N.S., Staahl C. et al. Subcutaneous Botulinum toxin type A reduces capsaicin-induced trigeminal pain and vasomotor reactions in human skin. Pain 2009;141(1–2):60–9.

36. Dolly J.O., O’Connell M.A. Neurotherapeutics to inhibit exocytosis from sensory neurons for the control of chronic pain. Curr Opin Pharmacol 2012;12:100–8.

37. Sutherland D.H., Kaufman K.R., Wyatt M.P. et al. Double-blind study of botulinum toxin injections into the gastrocnemius muscle in patients with cerebral palsy. Gait and Posture 1999;10:1–9.

38. Koman L.A., Mooney J.F. 3rd, Smith B.P. et al. Botulinum toxin type A neuromuscular blockade in the treatment of lower extremity spasticity in cerebral palsy: a randomized, double-blind, placebo-controlled trial. BOTOX Study Group. J Pediatr Orthop 2000;20(1):108–15.

39. Love S.C., Valentine J.P., Blair E.M. et al. The effect of botulinum toxin type A on the functional ability of the child with spastic hemiplegia a randomized controlled trial. Eur J Neurol 2001;8 (Suppl 5): 50–8.

40. Corry I.S., Cosgrove A.P., Duffy C.M. et al. Botulinum toxin A compared with stretching casts in the treatment of spastic equinus: a randomised prospective trial. J Pediatr Orthop 1998;18(3): 304–11.

41. Kirschner J., Berweck S., Mall V. et al. Botulinum toxin treatment in cerebral palsy: evidence for a new treatment option. J Neurol 2001;248(Suppl 1):28–30.

42. Koman L.A., Paterson Smith B., Balkrishnan R. Spasticity associated with cerebral palsy in children: guidelines for the use of botulinum A toxin. Paediatr Drugs 2003;5(1):11–23.

43. Naumann M., Albanese A., Heinen F. Safety and efficacy of botulinum toxin type A following long-term use. Eur J Neurol 2006;13 (Suppl 4):35–40.

44. Howell K., Selber P., Graham H.K., Reddihough D. Botulinum neurotoxin A: an unusual systemic effect. J Paediatr Child Health 2007;43(6):499–501.

45. Crowner B.E., Brunstrom J.E., Racette B.A. Iatrogenic botulism due to therapeutic botulinum toxin a injection in a pediatric patient. Clin Neuropharmacol 2007;30(5):310–3.

46. Sätilä H.K., Pietikäinen T., Lehtonen-Räty P. et al. Treatment of spastic equinus gait with botulinum toxin A: Does dose matter? Analysis of a clinical cohort. Neuropediatrics 2006;37(6):344–9.

47. Willis A.W., Crowner B., Brunstrom J.E. et al. High dose botulinum toxin A for the treatment of lower extremity hypertonicity in children with cerebral palsy. Dev Med Child Neurol 2007;49(11):818–22.

48. Molenaers G., Schörkhuber V., Fagard K. et al. Long-term use of botulinum toxin type A in children with cerebral palsy: treatment consistency. Eur J Paediatr Neurol 2009;13(5): 421–9.

49. Инструкция по применению лекарственного препарата для лекарственного применения Ботокс 100 ЕД. Регистрационный номер: П №011936/01, 2013.