Гетерогенность патофизиологических механизмов развития синдрома спастичности при различных заболеваниях ЦНС


DOI: https://dx.doi.org/10.18565/pharmateca.2020.3.26-37

С.Е. Хатькова (1, 2), Е.В. Костенко (3), М.А. Акулов (4), В.П. Дягилева (1, 2), Е.А. Николаев (1, 2), А.А. Бальберт (5), А.С. Орлова (6)

1) Национальный медицинский исследовательский центр, Москва, Россия; 2) Федеральный медицинский биофизический центр им. А.И. Бурназяна, Москва, Россия; 3) Российский национальный исследовательский медицинский университет им. Н.И. Пирогова, Москва, Россия; 4) Национальный научно-практический центр нейрохирургии им. акад. Н.Н. Бурденко, Москва, Россия; 5) Свердловский областной клинический психоневрологический госпиталь для ветеранов войн, Екатеринбург, Россия; 6) Первый Московский государственный медицинский университет им. И.М. Сеченова (Сеченовский Университет), Москва, Россия
Спастичность – это клиническое состояние, характеризующееся скорость-зависимым повышением мышечного тонуса или тонических сухожильных рефлексов в сочетании с другими симптомами поражения верхнего мотонейрона (СВМН). Спастичность считается положительным симптомом СВМН, в результате повреждения которого происходит потеря ингибирующего нисходящего влияния центральной нервной системы (ЦНС) на нижележащие структуры и развитие гиперчувствительности рефлекторных дуг на уровне спинного мозга. К развитию спастичности могут приводить различные заболевания: инсульт, детский церебральный паралич (ДЦП), травматическое повреждение головного мозга (ЧМТ – черепно-мозговая травма), спинномозговая травма (СМТ), рассеянный склероз (РС), нейродегенеративные и другие заболевания. В статье подробно рассмотрены особенности патофизиологии спастичности при различных заболеваниях, а также гетерогенность механизмов ее формирования. Представлены результаты современных исследований по эффективности ботулинического токсина типа А (БТА) в лечении фокальной спастичности разной этиологии (при инсульте, ДЦП, СМТ, ЧМТ, РС) как самостоятельного и адьювантного метода в совокупности с другими подходами при генерализованной спастичности. Для оценки эффективности БТА в лечении спастичности при данных заболеваниях необходимо проведение дальнейших исследований.
Ключевые слова: спастичность, инсульт, детский церебральный паралич, черепно-мозговая травма, спинномозговая травма, рассеянный склероз, боковой амиотрофический склероз, ботулинический токсин типа А

Литература


1. Ferrer P.M., Iñigo H.V., Juste D.J., et al. Systematic review of the treatment of spasticity in acquired adult brain damage. Rehabilit (Madr.). 2020;54(1):51–62. Doi: 10.1016/j.rh.2019.06.006.


2. Martin A., Abogunrin S., Kurth H., Dinet J. Epidemiological, humanistic, and economic burden of illness of lower limb spasticity in adults: a systematic review. Neuropsych Dis Treat. 2014;10:111–22. Doi: 10.2147/NDT.S53913.


3. Muñoz-Lasa S., López de Silanes C., Atín-Arratibel M.Á., et al. Effects of hippotherapy in multiple sclerosis: pilot study on quality of life, spasticity, gait, pelvic floor, depression and fatigue. Med Clin (Barc). 2019;152(2):55–8. Doi: 10.1016/j.medcli.2018.02.015.


4. Forsmark A., Rosengren L., Ertzgaard P. Inequalities in pharmacologic treatment of spasticity in Sweden – health economic consequences of closing the treatment gap. Health Econ Rev. 2020;10(1):4. Doi: 10.1186/s13561-020-0261-7.


5. Meijer R., Wolswijk A., Eijsden H.V. Prevalence, impact and treatment of spasticity in nursing home patients with central nervous system disorders: a cross-sectional study. Disabil Rehabil. 2017;39(4):363–71. Doi: 10.3109/09638288.2016.1146351.


6. Tranchida G.V., Van Heest A. Preferred options and evidence for upper limb surgery for spasticity in cerebral palsy, stroke, and brain injury. J Hand Surg Eur. 2020;45(1):34–42. Doi: 10.1177/1753193419878973.


7. Wood D.E., Burridge J.H., van Wijck F.M., et al. Biomechanical approaches applied to the lower and upper limb for the measurement of spasticity: a systematic review of the literature. Disabil Rehabil. 2005;27(1–2):19–32.


8. Pandyan A.D., Van Wijck F.M., Stark S., et al. The construct validity of a spasticity measurement device for clinical practice: an alternative to the Ashworth scales. Disabil Rehabil. 2006;28(9):579–85.


9. Sunnerhagen K.S., Opheim A., Alt Murphy M. Onset, time course and prediction of spasticity after stroke or traumatic brain injury. Ann Phys Rehabil Med. 2019;62(6):431–34. Doi: 10.1016/j.rehab.2018.04.004.


10. Li S., Francisco G.E. New insights into the pathophysiology of post-stroke spasticity. Front Hum Neurosci. 2015;9:192. Doi: 10.3389/fnhum.2015.00192.


11. Wissel J., Manack A., Brainin M. Toward an epidemiology of poststroke spasticity. Neurol. 2013;80(3):13–9. Doi: 10.1212/WNL.0b013e3182762448.


12. Burke D., Wissel J., Donnan G.A. Pathophysiology of spasticity in stroke. Neurol. 2013;80(3 Suppl. 2):S20–26. Doi: 10.1212/WNL.0b013e31827624a7.


13. Ward A.B. A literature review of the pathophysiology and onset of post-stroke spasticity. Eur J Neurol. 2012;19(1):21–7. Doi: 10.1111/j.1468-1331.2011.03448.x.


14. Asano S., Chantler P.D., Barr T.L. Gene expression profiling in stroke: relevance of blood-brain interaction. Curr Opin Pharmacol. 2016;26:80–6. Doi: 10.1016/j.coph.2015.10.004.


15. Дульнев В.В., Зуева Г.А., Кулова О.Ю. и др. Особенности эпидемиологии детского церебрального паралича у детей Тверской области. Бюллетень медицинских интернет-конференций. 2017;7(7):1350–52.


16. Haberfehlner H., Goudriaan M., Bonouvrié L.A., et al. Instrumented assessment of motor function in dyskinetic cerebral palsy: a systematic review. J Neuroeng Rehabil. 2020;17(1):39. Doi: 10.1186/s12984-020-00658-6.


17. Mathewson M.A., Lieber R.L. Pathophysiology of muscle contractures in cerebral palsy. Phys Med Rehabil Clin N Am. 2015;26(1):57–67. Doi: 10.1016/j.pmr.2014.09.005.


18. Flanigan M., Gaebler-Spira D., Kocherginsky M., et al. Spasticity and pain in adults with cerebral palsy. Dev Med Child Neurol. 2020;62(3):379–85. Doi: 10.1111/dmcn.14368.


19. 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 Neurol. 1997;39(4):214–23.


20. Баранов А.А. Федеральные клинические рекомендации по оказанию медицинской помощи детям с детским церебральным параличом. M., 2015.


21. Laxe S. Which interventions are useful for managing muscle spasticity in individuals who sustained traumatic brain injury? – A Cochrane Review summary with commentary. NeuroRehabilit. 2019;44(1):157–59. Doi: 10.3233/NRE-189003.


22. Sulhan S., Lyon K.A., Shapiro L.A., Huang J.H. Neuroinflammation and blood-brain barrier disruption following traumatic brain injury: Pathophysiology and potential therapeutic targets. J Neurosci Res. 2020;98(1):19–28. Doi: 10.1002/jnr.24331.


23. Williams O.H., Tallantyre E.C., Robertson N.P. Traumatic brain injury: pathophysiology, clinical outcome and treatment. J Neurol. 2015;262(5):1394–96. Doi: 10.1007/s00415-015-7741-4.


24. Pattuwage L., Olver J., Martin C., et al. Management of Spasticity in Moderate and Severe Traumatic Brain Injury: Evaluation of Clinical Practice Guidelines. J Head Trauma Rehabil. 2017;32(2):1–12. Doi: 10.1097/HTR.0000000000000234.


25. Baagøe S.K., Kofoed-Hansen M., Poulsen I., Riberholt C.G. Development of muscle contractures and spasticity during subacute rehabilitation after severe acquired brain injury: a prospective cohort study. Brain Inj. 2019;33(11):1460–66. Doi: 10.1080/02699052.2019.1646433.


26. Sangari S., Lundell H., Kirshblum S., Perez M.A. Residual descending motor pathways influence spasticity after spinal cord injury. Ann Neurol. 2019;86(1):28–41. Doi: 10.1002/ana.25505.


27. Luo D., Wu G., Ji Y., et al. The comparative study of clinical efficacy and safety of baclofen vs tolperisone in spasticity caused by spinal cord injury. Saudi Pharm J. 2017;25(4):655–59. Doi: 10.1016/j.jsps.2017.04.041.


28. Cha S., Yun J.H., Myong Y., Shin H.I. Spasticity and preservation of skeletal muscle mass in people with spinal cord injury. Spinal Cord. 2019;57(4):317–23. Doi: 10.1038/s41393-018-0228-2.


29. Finnerup N.B. Neuropathic pain and spasticity: intricate consequences of spinal cord injury. Spinal Cord. 2017;55(12):1046–50. Doi: 10.1038/sc.2017.70.


30. Norbye A.D., Midgard R., Thrane G. Spasticity, gait, and balance in patients with multiple sclerosis: A cross-sectional study. Physiother Res Int. 2020;25(1):1799. Doi: 10.1002/pri.1799.


31. Gracies J.M. Pathophysiology of spastic paresis. II: emergence of muscle over activity. Muscle Nerve. 2005;31(5):552–71.


32. Crone C., Johnsen L.L., Biering-Srensen F., Nielsen J.B.Appearance of reciprocal facilitation of ankle extensors fromankle flexors in patients with stroke or spinal cord injury. Brain. 2003;126(pt. 2):495–507.


33. Izquierdo G. Multiple sclerosis symptoms and spasticity management: new data. Neurodegener. Dis Manag. 2017;7(Suppl. 6):7–11. Doi: 10.2217/nmt-2017-0034.


34. Kheder A., Nair K.P.S. Spasticity: pathophysiology, evaluation and management. Pract Neurol. 2012;12:289–98.


35. Trompetto C., Currà A., Puce L., et al. Ghost spasticity in multiple sclerosis. J Electromyogr Kinesiol. 2020;51:102408. Doi: 10.1016/j.jelekin.2020.102408.


36. Schell W.E., Mar V.S., Da Silva C.P. Correlation of falls in patients with Amyotrophic Lateral Sclerosis with objective measures of balance, strength, and spasticity. NeuroRehabilit. 2019;44(1):85–93. Doi: 10.3233/NRE-182531.


37. Kiernan M.C., Vucic S., Cheah B.C., et al. Amyotrophic lateral sclerosis. Lancet. 2011;377(9769):942–55. Doi: 10.1016/S0140-6736(10)61156-7.


38. Dupuis L., Loeffler J.P. Neuromuscular junction destruction during amyotrophic lateral sclerosis: insights from transgenic models. Curr Opin Pharmacol. 2009;9(3):341–46. Doi: 10.1016/j.coph.2009.03.007


39. Ditunno J.F., Little J.W., Tessler A., Burns A.S. Spinal shock revisited: a four-phase model. Spinal Cord. 2004;42:383–95.


40. Mukherjee A., Chakravarty A. Spasticity mechanisms – for the clinician. Front Neurol. 2010;1:149.


41. Malhotra S., Pandyan A.D., Rosewilliam S., et al. Spasticity and contractures at the wrist after stroke: Time course of development and their association with functional recovery of the upper limb. Clin Rehabil. 2011;25(2):184–91. Doi: 10.1177/0269215510381620.


42. Picelli A., Tamburin S., Gajofatto F., et al. Association between severe upper limb spasticity and brain lesion location in stroke patients. Biomed Res Int. 2014;2014:162754. Doi: 10.1155/2014/162754.


43. Dentel C., Palamiuc L., Henriques A., et al. Degeneration of serotonergic neurons in amyotrophic lateral sclerosis: a link to spasticity. Brain. 2013;136(Pt. 2):483–93. Doi: 10.1093/brain/aws274.


44. Achache V., Roche N., Lamy J., et al. Transmission within several spinal pathways in adults with cerebral palsy. Brain. 2010;133(Pt. 5):1470–83. Doi: 10.1093/brain/awq053.


45. Kheder A., Nair K.P. Spasticity: pathophysiology, evaluation and management. Pract Neurol. 2012;12(5):289–98. Doi: 10.1136/practneurol-2011-000155.


46. Райхель Г. Терапевтическое руководство спастичность-дистония. 1-е изд. Бремен: УНИ-МЕД, 2013. C. 12–3.


47. Hiersemenzel L.P., Curt A., Dietz V. From spinal shock to spasticity: neuronal adaptations to a spinal cord injury. Neurol. 2000;54(8):1574–82.


48. Esquenazi A., Albanese A., Chancellor M.B., et al. Evidence-based review and assessment of botulinum neurotoxin for the treatment of adult spasticity in the upper motor neuron syndrome. Toxicon. 2013;67:115–28.


49. Burbaud P., Wiart L., Dubos J.L., et al. A randomised, double blind, placebo controlled trial of botulinum toxin in the treatment of spastic foot in hemiparetic patients. J Neurol. Neurosurg Psychiatry. 1996;61(3):265–69.


50. Reiter F., Danni M., Lagalla G., et al. Low-dose botulinum toxin with ankle taping for the treatment of spastic equinovarus foot after stroke. Arch Phys Med Rehabil. 1998;79(5):532–35.


51. Farina S., Migliorini C., Gandolfi M., et al. Combined effects of botulinum toxin and casting treatments on lower limb spasticity after stroke. Funct Neurol. 2008;23(2):87–91.


52. Yan X., Lan J., Liu Y., Miao J. Efficacy and Safety of Botulinum Toxin Type A in Spasticity Caused by Spinal Cord Injury: A Randomized, Controlled Trial Med Sci Monit. 2018;24:8160–71. Doi: 10.12659/MSM.911296.


53. Gracies J.M., O’Dell M., Vecchio M., et al.; Effects of repeated abobotulinumtoxinA injections in upper limb spasticity. Muscle Nerve 2018;57: 245–54. DOI: 10.1002/mus.25721.


54. Gracies J.M., Esquenazi A., Brashear A., et al.; International AbobotulinumtoxinA Adult Lower Limb Spasticity Study Group. Efficacy and safety of abobotulinumtoxinA in spastic lower limb: Randomized trial and extension. Neurol. 2017;89(22):2245–53. Doi: 10.1212/WNL.0000000000004687.


55. McAllister P.J., Khatkova S.E., Faux S.G., et al. Effects on walking of simultaneous upper/lower limb abobotulinumtoxina injections in patients with stroke or brain injury with spastic hemiparesis. J Rehabil Med. 2019;51(10):813–16. Doi: 10.2340/16501977-2604.


56. Laxe S. Which interventions are useful for managing muscle spasticity in individuals who sustained traumatic brain injury? – A Cochrane Review summary with commentary. NeuroRehabilit. 2019;44(1):157–59. Doi: 10.3233/NRE-189003.


57. Graham H.K. Botulinum toxin A in cerebral palsy: functional outcomes. J Pediatr. 2000;137(3):300e–303.


58. Koman L.A., Smith B.P., Williams R., et al. Upper extremity spasticity in children with cerebral palsy: a randomized, double-blind, placebo-controlled study of the short-term outcomes of treatment with botulinum A toxin. J Hand Surg Am. 2013;38(3):435–61.


59. Olesch C.A., Greaves S., Imms C., et al. Repeat botulinum toxin-A injections in the upper limb of children with hemiplegia: a randomized controlled trial. Dev Med Child Neurol. 2010;52(1):79–86.


60. Blumetti F.C., Belloti J.C., Tamaoki M.J., Pinto J.A. Botulinum toxin type A in the treatment of lower limb spasticity in children with cerebral palsy. Cochrane Database Syst Rev. 2019;10:CD001408. Doi: 10.1002/14651858.CD001408.pub2.


61. Lui J., Sarai M., Mills P.B. Chemodenervation for treatment of limb spasticity following spinal cord injury: a systematic review. Spinal Cord. 2015;53(4):252–64. Doi: 10.1038/sc.2014.241.


62. Yan X., Lan J., Liu Y., Miao J. Efficacy and Safety of Botulinum Toxin Type A in Spasticity Caused by Spinal Cord Injury: A Randomized, Controlled Trial. Med Sci Monit. 2018;24:8160–71. Doi: 10.12659/MSM.911296.


63. Palazón-García R., Alcobendas-Maestro M., Esclarin-de Ruz A., Benavente-Valdepeñas A.M. Treatment of spasticity in spinal cord injury with botulinum toxin. J Spinal Cord Med. 2019;42(3):281–87. Doi: 10.1080/10790268.2018.1479053.


64. Grazko M.A., Polo K.B., Jabbari B. Botulinum toxin A for spasticity, muscle spasms, and rigidity. Neurol. 1995;45:712–17.


65. Hyman N., Barnes M., Bhakta B., et al. Botulinum toxin (Dysport) treatment of hip adductor spasticity in multiple sclerosis: a prospective, randomised, double blind, placebo controlled, dose ranging study. J Neurol Neurosurg Psych. 2000;68:707–12.


66. Giovannelli M., Borriello G., Castri P., et al. Early physiotherapy after injection of botulinum toxin increases the beneficial effects on spasticity in patients with multiple sclerosis. Clin Rehabil. 2007;21(4):331–37.


67. Paoloni M., Giovannelli M., Mangone M., et al. Does giving segmental muscle vibration alter the response to botulinum toxin injections in the treatment of spasticity in people with multiple sclerosis? A single-blind randomized controlled trial. Clin Rehabil. 2013;27(9):803–12. Doi: 10.1177/0269215513480956.


68. Latino P., Castelli L., Prosperini L., et al. Determinants of botulinum toxin discontinuation in multiple sclerosis: a retrospective study. Neurol Sci. 2017;38(10):1841–48. Doi: 10.1007/s10072-017-3078-3.


69. Marvulli R., Megna M., Citraro A., et al. Botulinum Toxin Type A and Physiotherapy in Spasticity of the Lower Limbs Due to Amyotrophic Lateral Sclerosis. Toxins (Basel). 2019;11(7). Doi: 10.3390/toxins11070381.


70. Инструкция FDA. URL: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/125274s115lbl.pdf


71. Инструкция по медицинскому применению препарата Диспорт® 500/300 ЕД. [Instructions for medical use of the drug Dysport® 500/300 UNITS. (In Russ.). URL: https://grls.rosminzdrav.ru


Об авторах / Для корреспонденции


Автор для связи: С.Е. Хатькова, д.м.н., профессор, Национальный медицинский исследовательский центр; Федеральный медицинский биофизический центр им. А.И. Бурназяна, Москва, Россия; e-mail: Hse15@mail.ru 
Адрес: 125367, Россия, Москва, Иваньковское ш., 3


ORCID:
С.Е. Хатькова, ORCID: https://orcid.org/0000-0002-3071-4712 
Е.В. Костенко, ORCID: http://orcid.org/0000-0003-0629-9659 
М.А. Акулов, ORCID: https://orcid.org/0000-0002-6191-424X 
В.П. Дягилева, ORCID: http://orcid.org/0000-0002-7424-7167 
Е.А. Николаев, ORCID: http://orcid.org/0000-000304433201 
А.А. Бальберт, ORCID: http://orcid.org/0000-0001-7164-0003 
А.С. Орлова, ORCID: http://orcid.org/0000-0001-9725-7491 


Бионика Медиа