In search of the “gold standard” for the treatment of post-stroke upper limb spasticity

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Since the advent of botulinum toxin type A (BT-A) preparations, trials to study their efficacy, safety, doses and routes of administration, and their impact on the lives of patients and caregivers have been conducted worldwide. To date, extensive experience has been accumulated in the use of botulinum therapy for various conditions, including spasticity. The review is devoted to the use of BT-A preparations for post-stroke spasticity in the arm. The capabilities and limitations of the method are considered.

Full Text

Restricted Access

About the authors

Anna V. Serdyuk

Pirogov Russian National Research Medical University

Author for correspondence.
Email: aserdyuk@gmail.com
ORCID iD: 0000-0002-9287-966X

Cand. Sci. (Med.), Associate Professor, Department of Fundamental and Clinical Neurology, Neurosurgery and Medical Genetics

Russian Federation, Moscow

References

  1. Толмачева В.А. Постинсультнаяя спастичность, индивидуализированный подход к лечению. Неврология, нейропсихиатрия, психосоматика. 2016;8(4):71–6. [Tolmacheva V.A. Poststroke spasticity: an individualized approach to treatment. Neurol Neuropsych Psychosomat. 2016;8(4):71–6. (In Russ.)]. https://doi.org/10.14412/2074-2711-2016-4-71-76
  2. Катушкина Э.А., Зиновьева О.Е. Постинсультная спастичность: современное состояние проблемы, методы лечения. Врач. 2014;(9):8–12. [Katushkina E.A., Zinovyeva O.E. Poststroke spasitily: сurrent state of the problem, treatment methods. Vrach. 2014;(9):8–12. (In Russ.)].
  3. Костенко Е.В., Петрова Л.В., Ганжула П.А. и др. Опыт применения ксеомина в коррекции спастичности руки в ранний восстановительный период инсульта. Журнал неврологии и психиатрии им С.С. Корсакова. 2012;(2):29–34. [Kostenko E.V., Petrova L.V., Ganzhula P.A., et al. Experience in using xeomin in the treatment of arm and hand spasticity in the early rehabilitation phase of stroke. J Nevrol Psikh Im S.S. Korsakova. 2012;(2):29–34. (In Russ.)].
  4. Королев А.А. Постинсультная спастичность: особенности развития, клиническая оценка и принципы реабилитации. Паллиативная медицина и реабилитация. 2011;(3):51–4. [Korolev А.А. Poststroke spasitily: developmental features, clinical assessment and principles of rehabilitation. Palliat Med Rehabilitat. 2011;(3):51–4. (In Russ.)].
  5. Хатькова C.E. Лечение спастичности после инсульта Неврология, нейропсихиатрия, психосоматика. 2010;2(3):76–80. [Khatkova S.E. Treatment for spasticity after stroke. Neurol Neuropsych Psychosomat. 2010;2(3):76–80. (In Russ.)]. https://doi.org/10.14412/2074-2711-2010-106
  6. Катушкина Е.А., Зиновьева O.E., Шенкман Б.С., Яхно Н.Н. Механизмы патогенеза постинсультной спастичности. Неврология, нейропсихология, психосоматикa. 2011;3(4):14–8. [Katushkina E.A., Zinovyeva O.E., Shenkman B.S., Yakhno N.N. Neuropsychiatry, Psychosomatics Mechanisms in the pathogenesis of poststroke spasticity. Neurol Neuropsych Psychosomat. 2011;3(4):14–8. (In Russ.)].
  7. Xia Y., et al. Microglia-derived TNF-α contributes to central sensitization in spasticity after stroke. J Neuroinflammation. 2023;20(1):45. https://doi.org/10.1186/s12974-023-02734-9
  8. Lopez-Valdes, H.E., et al. Astrocytic glutamate uptake dysfunction promotes hyperexcitability and spasticity after stroke. Glia. 2022;70(5):876–94. https://doi.org/10.1002/glia.24145
  9. Shi Y., et al. Neuroinflammation drives spasticity via astrocyte-microglia cross-talk. Nat Commun. 2021;12:5173. https://doi.org/10.1038/s41467-021-25464-z
  10. Liu X., et al. Kv1.1 downregulation in spinal motoneurons promotes spasticity after stroke. J Neurosci. 2022;42(15):3120–35. https://doi.org/10.1523/JNEUROSCI.0123-22.2022
  11. Ritter D.M., et al. Kv3.4 channels control motoneuron hyperexcitability in spasticity. Cell Rep. 2021;34(6):108730. https://doi.org/10.1016/j.celrep.2021.108730
  12. Typlt C., et al. BKса channel deficiency leads to hyperexcitability and spasticity after spinal cord injury. Neuron. 2023;110(5):789–804. https://doi.org/10.1016/j.neuron.2023.01.010
  13. Boulenguez P., et al. Down-regulation of the potassium-chloride cotransporter KCC2 contributes to spasticity after spinal cord injury. Nat Med. 2010;16(3):302–7. https://doi.org/10.1038/nm.2107.
  14. Yan J., et al. Cav1.3 blockade reduces spasticity in rats after spinal cord injury. Cell Rep. 2021;34(13):108876. https://doi.org/10.1016/j.celrep.2021.108876
  15. Falcone N., Leo F., Chisari C., Dalise S. Long-term management of post-stroke spasticity with botulinum toxin: a retrospective study. Eur J Phys Rehabil. Med. 2023;59(2):234–41. https://doi.org/10.23736/S1973-9087.23.07745-9
  16. Ye D.H., Chun M.H., Park Y.G., et al. A randomized, double-blind, active control, multicenter, phase 3 study to evaluate the efficacy and safety of Liztox® versus Botox® in post-stroke upper limb spasticity. Clin Rehabil. 2023;37(8):1045–56. https://doi.org/10.1177/02692155231152841
  17. Костенко Е.В., Петрова Л.В. Комплексная реабилитация пациентов с постинсультной спастичностью в нижней конечности. Эффективность применения ботулотоксина. Медицинский совет. 2016;(11):92–9. [Kostenko E.V., Petrova L.V. [Comprehensive rehabilitation of patients with post-stroke spasticity in the lower limb: Efficacy of botulinum toxin use. Medical Councilium. 2016;(11):92–9. (In Russ.)]. https://doi.org/10/21518/2079-701X-2016-11-92-99
  18. Барулин Л.Е., Курушина O.В. Лечение постинсультной спастичности (шаг за шагом). Русский медицинский журнал. 2014;(10):732–5. [Barulin L.E., Kurushina O.V. Treatment of post-stroke spasticity (step by step). Rus Med J. 2014;(10):732–5. (In Russ.)].
  19. Королев А.А., Выбор фармакологической терапии при спастическом мышечном гипертонусе. Лечащий врач. 2013;(2). [Korolev A.A. Pharmacological therapy selection for spastic muscle hypertonus. Lech Vrach. 2013;(2). (In Russ.)].
  20. Парфенов В.А. Ведение больных, перенесших инсульт и имеющих спастичность. Эффективная фармакотерапия. 2015;(39):28–34. [Parfenov V.A. Management of post-stroke patients with spasticity. Effect Pharmacother. 2015;(39):28–34. (In Russ.)].
  21. Kaku M., Simpson D.M. Spotlight on botulinum toxin and its potential in the treatment of stroke-related spasticity. J Neurol Sci. 2022;434:120154. https://doi.org/10.1016/j.jns.2022.120154
  22. Костенко Е.В., Постинсультные болевые синдромы: клинические аспекты, диагностические критерии, особенности терапии и реабилитационных мероприятий. Медицинский совет. 2017;(17):63–71. [Kostenko E.V. Post-stroke pain syndromes: clinical aspects, diagnostic criteria, features of therapy and rehabilitation measures. Med Council. 2017;(17):63–71. (In Russ.)]. https://doi.org/10.21518/2079-701X-2017-17-63-71
  23. Лихачев С.А., Рушкевич Ю.Н. Спастичность: клинико-патофизиологические особенности и ботулинотерапия. Неврология и нейрохирургия Восточной Европы. 2020;10(3):471. [Likhachev S.A., Rushkevich Yu.N. Spasticity: Clinical and Pathophysiological Features and Botulinum Therapy. Neurol Neurosurg Eastern Eur. 2020;10(3):471. (In Russ.)].
  24. Dong M., et al. Molecular basis of botulinum neurotoxin serotype A binding to nerve cells. Nat Commun. 2019;10:418. https://doi.org/10.1038/s41467-018-08134-5
  25. Pirazzini M., et al. Botulinum neurotoxins: biology, pharmacology, and toxicology. Pharmacol Rev. 2017;69(2):200–35. https://doi.org/10.1124/pr.116.012658
  26. Ravichandran E., et al. Pharmacokinetic studies of botulinum neurotoxin type A1 and A2 in rats. Toxins. 2021;13(2):146. doi: 10.3390/toxins13020146
  27. Королев А.А. Суслова Г.А. Нейрореабилитация: современные технологии восстановительного лечения постинсультной спастичности. Фундаментальные исследования. 2012;7(часть 2):344–9. [Korolev A.A., Suslova G.A. Neurorehabilitation: Modern Technologies for Restorative Treatment of Post-Stroke Spasticity. Fund Res. 2012;7(часть 2):344–9. (In Russ.)].
  28. Esquenazi A., Jost W.H., Turkel C.C., et al. Treatment of adult spasticity with Botox (onabotulinumtoxinA): Development, insights, and impact. PM R. 2023;15(4):503–15. https://doi.org/10.1002/pmrj.12834
  29. Колбин А.С., Вилюм И.А., Проскурин М.А. Балыкина Ю.Е. Фармакоэкономический анализ препаратов ботулотоксина в комплексной терапии постинсультной спастичности. Качественная клиническая практика. 2015;(3):19–29. [Kolbin A.S., Vilum I.A., Proskurin M.A., Balykina Yu.E. Pharmacoeconomic analysis of the use of botulinum toxin in the treatment of poststroke spasticity. Good Clin Pract. 2015;(3):19–29. (In Russ.)].
  30. Sheean G. Botulinum toxin should be first-line treatment for poststroke spasticity. J Neurol Neurosurg Psych. 2015;86(3):239–41. doi: 10.1136/jnnp-2014-308740.
  31. Хатькова C.Е., Гильвег М.А. Моделирование отдаленных результатов и рисков смерти у пациентов с постинсультной спастичностью при проведении инъекций абоботулотоксина в структуре реабилитации. Неврология, нейропсихиатрия, психосоматика. 2024;16(2):60–8. [Khatkova S.E., Gilveg M.A. Modeling long-term outcomes and mortality risks in patients with post-stroke spasticity receiving AbobotulinumtoxinA injections as part of rehabilitation. Neurol Neuropsych Psychosomat. 2024;16(2):60–8. (In Russ.)].
  32. Jost W.H., Brown S., Gess K. Comparative cost-effectiveness of incobotulinumtoxinA for post-stroke spasticity: a cost-utility analysis. J Med Econ. 2015;18(7):556–62. https://doi.org/10.3111/13696998.2015.1038279
  33. Петрова С.В., Иванов А.Б., Сидорова К.Л. и др. Анализ стоимости лечения спастичности в условиях российских клиник. Неврологический журнал. 2021;3:45–52. [Petrova S.V., Ivanov A.B., Sidorova K.L., et al. Cost-analysis of spasticity treatment in Russian clinical practice. Neurol J. 2021;(3):45–52. (In Russ.)].
  34. Truong D., Goyal S., Leskin A. Pharmacoeconomic analysis of type A botulinum toxins for spasticity: focus on long-term costs. Neurol Clin Pract. 2020;10(4):312–20. https://doi.org/10.1212/CPJ.0000000000000734
  35. Andringa A., van de Port I., van Wegen E., et al. Effectiveness of botulinum toxin treatment for upper limb spasticity poststroke over different ICF domains: a systematic review and meta-analysis. Arch Phys Med Rehabil. 2023;104(5):732–46. https://doi.org/10.1016/j.apmr.2022.10.006
  36. Ozcakir S., Sivrioglu K. Botulinum toxin in poststroke spasticity. Clin Med Res. 2007;5(2):132–8. https://doi.org/10.3121/cmr.2007.716
  37. Simpson D.M., et al. OnabotulinumtoxinA injection for poststroke upper-limb spasticity: Guidance for early injectors from a Delphi panel process. Muscle Nerve. 2022;66(6):671–9. https://doi.org/10.1002/mus.27706
  38. Antonucci F., et al. Long distance ratrograde effects of botulinum neurotoxin A (BoNT/A). J Neurosci. 2008;28(14):3689–96. https://doi.org/10/1523/JNEUROSCI.03-75-08.2008
  39. Restani L., et al. Evidence for anterograde transport and transcytosis of botulinum neurotoxin A (BoNT/A). J Neurosci. 2012;32(34):11509–18. https://doi.org/10.1523/JNEUROSCI.4923-11.2012
  40. Dressler D., et al. Botulinum toxin therapy: risk factors for therapy failure. Mov Disord Clin Pract. 2017;4(5):728–33. https://doi.org/10.1002/mdc3.1253.
  41. Jia S., Liu Y., Shen L., et al. Botulinum toxin type A for upper limb spasticity in poststroke patients: a meta-analysis of randomized controlled trials. Medicine (Baltimore). 2020;99(29):e21291. https://doi.org/10.1097/MD.0000000000021291
  42. Gracies J.M., Brashear A., Jech R., et al. Safety and efficacy of abobotulinumtoxinA for hemiparesis in adults with upper limb spasticity after stroke: a randomized, double-blind, placebo-controlled trial. Neurology. 2015;85(1):1–9. https://doi.org/10.1212/WNL.0000000000001747
  43. Fawzi S.M., Hamdan F.B., Jaafar I.F., Al Gawwam G.A.S. Botulinum neurotoxin-A in a patient with post-stroke spasticity: a neurophysiological study. Neurol Sci. 2023;44(5):1789–96. https://doi.org/10.1007/s10072-023-06647-6
  44. Jacinto J., Balbert A., Bensmail D., et al. Selecting goals and target muscles for botulinum toxin A injection using the Goal Oriented Facilitated Approach to Spasticity Treatment (GO-FAST) tool. J Rehabil Med. 2023;55:jrm00389. https://doi.org/10.2340/jrm.v55.2765
  45. Elia A.E., Filippini G., Calandrella D., Albanese A. Botulinum neurotoxins for post-stroke spasticity in adults: a systematic review. Toxins (Basel). 2022;14(8):523. https://doi.org/10.3390/toxins14080523.
  46. Шихкеримов Р.К., Истомина Е.В. Рекомбинантные ботулотоксины как новый этап развития ботулинотерапии. Возможности и перспективы применения в неврологической практике. Неврология, нейропсихиатрия, психосоматика. 2022;14(6):103–9. [Shikhkerimov R.K., Istomina E.V. Recombinant botulinum toxins: expanding horizons of neurological botulinum therapy. Neurol Neuropsych Psychosomat. 2022;14(6):103–9. (In Russ.)]. https://doi.org/10.14412/2074-2711-2022-6-103-109

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 2025 Bionika Media