The Non-Affected Muscle Volume Compensates for the Partial Loss of Strength after Injection of Botulinum Toxin A
Abstract
:1. Introduction
2. Results
2.1. BTX-A-Injection
2.2. Clinical Examination
2.3. MRI
2.4. Gait and Musculoskeletal Modelling Analysis
3. Discussion
4. Methods
4.1. Ethical Considerations
4.2. Participants
4.3. Treatment
4.4. MRI
4.5. Gait Analysis
4.6. Musculoskeletal Modelling
4.7. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Palisano, R.; Rosenbaum, P.; Walter, S.; Russell, D.; Wood, E.; Galuppi, B. Development and reliability of a system to classify gross motor function in children with cerebral palsy. Dev. Med. Child Neurol. 1997, 39, 214–223. [Google Scholar] [CrossRef]
- Lance, J.W. Symposium synopsis. In Spasticity: Disordered Motor Control; Young, R.R., Koella, W.P., Eds.; Yearbook Medical Publishers: Chicago, IL, USA, 1980; pp. 485–494. [Google Scholar]
- Van Den Noort, J.C.; Bar-On, L.; Aertbeliën, E.; Bonikowski, M.; Braendvik, S.M.; Broström, E.W.; Buizer, A.I.; Burridge, J.H.; Van Campenhout, A.; Dan, B.; et al. European consensus on the concepts and measurement of the pathophysiological neuromuscular responses to passive muscle stretch. Eur. J. Neurol. 2017, 24, 981.e38. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rutz, E.; Hofmann, E.; Brunner, R. Preoperative botulinum toxin test injections before muscle lengthening in cerebral palsy. J. Orthop. Sci. 2010, 15, 647–653. [Google Scholar] [CrossRef]
- Multani, I.; Manji, J.; Hastings-Ison, T.; Khot, A.; Graham, K. Botulinum Toxin in the Management of Children with Cerebral Palsy. Pediatr. Drugs 2019, 21, 261–281. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mathevon, L.; Michel, F.; Decavel, P.; Fernandez, B.; Parratte, B.; Calmels, P. Muscle structure and stiffness assessment after botulinum toxin type A injection. A systematic review. Ann. Phys. Rehabilit. Med. 2015, 58, 343–350. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Heinen, F.; Desloovere, K.; Schroeder, A.S.; Berweck, S.; Borggraefe, I.; van Campenhout, A.; Andersen, G.L.; Aydin, R.; Becher, J.G.; Bernert, G.; et al. The updated European Consensus 2009 on the use of Botulinum toxin for children with cerebral palsy. Eur. J. Paediatr. Neurol. 2010, 14, 45–66. [Google Scholar] [CrossRef] [PubMed]
- Heinen, F.; Molenaers, G.; Fairhurst, C.; Carr, L.J.; Desloovere, K.; Valayer, E.C.; Morel, E.; Papavassiliou, A.S.; Tedroff, K.; Pascual-Pascual, S.I.; et al. European consensus Table 2006 on botulinum toxin for children with cerebral palsy. Eur. J. Paediatr. Neurol. 2006, 10, 215–225. [Google Scholar] [CrossRef] [PubMed]
- Nieuwenhuys, A.; Papageorgiou, E.; Pataky, T.; De Laet, T.; Molenaers, G.; Desloovere, K. Literature Review and Comparison of Two Statistical Methods to Evaluate the Effect of Botulinum Toxin Treatment on Gait in Children with Cerebral Palsy. PLoS ONE 2016, 11, e0152697. [Google Scholar] [CrossRef]
- Graham, H.; Aoki, K.; Autti-Rämö, I.; Boyd, R.N.; Delgado, M.R.; Gaebler-Spira, D.J.; Gormley, M.E.; Guyer, B.M.; Heinen, F.; Holton, A.F.; et al. Recommendations for the use of botulinum toxin type A in the management of cerebral palsy. Gait Posture 2000, 11, 67–79. [Google Scholar] [CrossRef]
- Sätilä, H. Over 25 Years of Pediatric Botulinum Toxin Treatments: What Have We Learned from Injection Techniques, Doses, Dilutions, and Recovery of Repeated Injections? Toxins 2020, 12, 440. [Google Scholar] [CrossRef]
- Bar-On, L.; Aertbeliën, E.; Van Campenhout, A.; Molenaers, G.; Desloovere, K. Treatment Response to Botulinum Neurotoxin-A in Children with Cerebral Palsy Categorized by the Type of Stretch Reflex Muscle Activation. Front. Neurol. 2020, 11, 378. [Google Scholar] [CrossRef] [PubMed]
- Read, F.A.; Boyd, R.N.; Barber, L.A. Longitudinal assessment of gait quality in children with bilateral cerebral palsy following repeated lower limb intramuscular Botulinum toxin-A injections. Res. Dev. Disabil. 2017, 68, 35–41. [Google Scholar] [CrossRef] [PubMed]
- Pingel, J.; Wienecke, J.; Lorentzen, J.; Nielsen, J.B. Botulinum toxin injection causes hyper-reflexia and increased muscle stiffness of the triceps surae muscle in the rat. J. Neurophysiol. 2016, 116, 2615–2623. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dressler, D.; Saberi, F.A. Botulinum Toxin: Mechanisms of Action. Eur. Neurol. 2005, 53, 3–9. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kao, I.; Drachman, D.B.; Price, D.L. Botulinum Toxin: Mechanism of Presynaptic Blockade. Science 1976, 193, 1256–1258. [Google Scholar] [CrossRef]
- Simpson, L.L. Identification of the Major Steps in Botulinum Toxin Action. Annu. Rev. Pharmacol. Toxicol. 2004, 44, 167–193. [Google Scholar] [CrossRef]
- Wheeler, A.; Smith, H.S. Botulinum toxins: Mechanisms of action, antinociception and clinical applications. Toxicology 2013, 306, 124–146. [Google Scholar] [CrossRef]
- Weidensteiner, C.; Madoerin, P.; Deligianni, X.; Haas, T.; Bieri, O.; D’Antonoli, T.A.; Bracht-Schweizer, K.; Romkes, J.; De Pieri, E.; Santini, F.; et al. Quantification and Monitoring of the Effect of Botulinum Toxin A on Paretic Calf Muscles of Children with Cerebral Palsy With MRI: A Preliminary Study. Front. Neurol. 2021, 12, 630435. [Google Scholar] [CrossRef]
- Boyd, R.N.; Hays, R.M. Current evidence for the use of botulinum toxin type A in the management of children with cerebral palsy: A systematic review. Eur. J. Neurol. 2001, 8, 1–20. [Google Scholar] [CrossRef] [Green Version]
- Edgar, T.S. Clinical utility of botulinum toxin in the treatment of cerebral palsy: Comprehensive review. J. Child Neurol. 2001, 16, 37–46. [Google Scholar] [CrossRef]
- Lannin, N.; Scheinberg, A.; Clark, K. AACPDM systematic review of the effectiveness of therapy for children with cerebral palsy after botulinum toxin A injections. Dev. Med. Child Neurol. 2006, 48, 533–539. [Google Scholar] [CrossRef]
- Desloovere, K.; Schörkhuber, V.; Fagard, K.; Van Campenhout, A.; De Cat, J.; Pauwels, P.; Ortibus, E.; De Cock, P.; Molenaers, G. Botulinum toxin type A treatment in children with cerebral palsy: Evaluation of treatment success or failure by means of goal attainment scaling. Eur. J. Paediatr. Neurol. 2012, 16, 229–236. [Google Scholar] [CrossRef]
- Wesseling, M.; Kainz, H.; Hoekstra, T.; Van Rossom, S.; Desloovere, K.; De Groote, F.; Jonkers, I. Botulinum toxin injections minimally affect modelled muscle forces during gait in children with cerebral palsy. Gait Posture 2020, 82, 54–60. [Google Scholar] [CrossRef] [PubMed]
- De Pieri, E.; Romkes, J.; Wyss, C.; Brunner, R.; Viehweger, E. Altered Muscle Contributions are Required to Support the Stance Limb During Voluntary Toe-Walking. Front. Bioeng. Biotechnol. 2022, 10, 810560. [Google Scholar] [CrossRef] [PubMed]
- Löwing, K.; Thews, K.; Haglund-Åkerlind, Y.; Gutierrez-Farewik, E.M. Effects of Botulinum Toxin-A and Goal-Directed Physiotherapy in Children with Cerebral Palsy GMFCS Levels I & II. Phys. Occup. Ther. Pediatr. 2016, 37, 268–282. [Google Scholar] [CrossRef]
- Gough, M.; Shortland, A. The Musculoskeletal System in Children with Cerebral Palsy: A Philisophical Approach to Management; Mac Keith Press: London, UK, 2022. [Google Scholar]
- Fridén, J.; Lieber, R.L. Spastic muscle cells are shorter and stiffer than normal cells. Muscle Nerve 2003, 27, 157–164. [Google Scholar] [CrossRef] [PubMed]
- Lieber, R.L.; Steinman, S.; Barash, I.A.; Chambers, H. Structural and functional changes in spastic skeletal muscle. Muscle Nerve 2004, 29, 615–627. [Google Scholar] [CrossRef]
- Boulard, C.; Gross, R.; Gautheron, V.; Lapole, T. What causes increased passive stiffness of plantarflexor muscle–tendon unit in children with spastic cerebral palsy? Eur. J. Appl. Physiol. 2019, 119, 2151–2165. [Google Scholar] [CrossRef]
- Lieber, R.L.; Runesson, E.; Einarsson, F.; Fridén, J. Inferior mechanical properties of spastic muscle bundles due to hypertrophic but compromised extracellular matrix material. Muscle Nerve 2003, 28, 464–471. [Google Scholar] [CrossRef]
- Josenby, A.L.; Czuba, T.; Alriksson-Schmidt, A.I. Gender differences in treatments and interventions received by children and adolescents with cerebral palsy. BMC Pediatr. 2020, 20, 45. [Google Scholar] [CrossRef] [Green Version]
- Hilbert, T.; Sumpf, T.J.; Weiland, E.; Frahm, J.; Thiran, J.-P.; Meuli, R.; Kober, T.; Krueger, G. Accelerated T2 mapping combining parallel MRI and model-based reconstruction: GRAPPATINI. J. Magn. Reson. Imaging 2018, 48, 359–368. [Google Scholar] [CrossRef] [PubMed]
- Kadaba, M.P.; Ramakrishnan, H.K.; Wootten, M.E. Measurement of lower extremity kinematics during level walking. J. Orthop. Res. 1990, 8, 383–392. [Google Scholar] [CrossRef] [PubMed]
- Damsgaard, M.; Rasmussen, J.; Christensen, S.T.; Surma, E.; de Zee, M. Analysis of musculoskeletal systems in the AnyBody Modeling System. Simul. Model. Pract. Theory 2006, 14, 1100–1111. [Google Scholar] [CrossRef]
- Carbone, V.; Fluit, R.; Pellikaan, P.; van der Krogt, M.M.; Janssen, D.; Damsgaard, M.; Vigneron, L.; Feilkas, T.; Koopman, H.F.J.M.; Verdonschot, N. TLEM 2.0—A comprehensive musculoskeletal geometry dataset for subject-specific modeling of lower extremity. J. Biomech. 2015, 48, 734–741. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- De Pieri, E.; Lund, M.E.; Gopalakrishnan, A.; Rasmussen, K.P.; Lunn, D.; Ferguson, S.J. Refining muscle geometry and wrapping in the TLEM 2 model for improved hip contact force prediction. PLoS ONE 2018, 13, e0204109. [Google Scholar] [CrossRef]
- Lund, M.E.; Andersen, M.S.; de Zee, M.; Rasmussen, J. Scaling of musculoskeletal models from static and dynamic trials. Int. Biomech. 2015, 2, 1–11. [Google Scholar] [CrossRef]
- Wu, G.; Siegler, S.; Allard, P.; Kirtley, C.; Leardini, A.; Rosenbaum, D.; Whittle, M.; D’Lima, D.D.; Cristofolini, L.; Witte, H.; et al. ISB recommendation on definitions of joint coordinate system of various joints for the reporting of human joint motion—Part I: Ankle, hip, and spine. J. Biomech. 2002, 35, 543–548. [Google Scholar] [CrossRef]
- Andersen, M.S. Introduction to musculoskeletal modelling. In Computational Modelling of Biomechanics and Biotribology in the Musculoskeletal System; Elsevier: Amsterdam, The Netherlands, 2021; pp. 41–80. [Google Scholar]
- Arnold, A.S.; Liu, M.Q.; Schwartz, M.; Õunpuu, S.; Delp, S.L. The role of estimating muscle-tendon lengths and velocities of the hamstrings in the evaluation and treatment of crouch gait. Gait Posture 2006, 23, 273–281. [Google Scholar] [CrossRef]
- Laracca, E.; Stewart, C.; Postans, N.; Roberts, A. The effects of surgical lengthening of hamstring muscles in children with cerebral palsy—The consequences of pre-operative muscle length measurement. Gait Posture 2014, 39, 847–851. [Google Scholar] [CrossRef]
- Bar-On, L.; Molenaers, G.; Aertbeliën, E.; Monari, D.; Feys, H.; Desloovere, K. The relation between spasticity and muscle behavior during the swing phase of gait in children with cerebral palsy. Res. Dev. Disabil. 2014, 35, 3354–3364. [Google Scholar] [CrossRef]
- Kainz, H.; Schwartz, M.H. The importance of a consistent workflow to estimate muscle-tendon lengths based on joint angles from the conventional gait model. Gait Posture 2021, 88, 1–9. [Google Scholar] [CrossRef] [PubMed]
- Lund, M.; Rasmussen, J.; Andersen, M. AnyPyTools: A Python package for reproducible research with the AnyBody Modeling System. J. Open Source Softw. 2019, 4, 1108. [Google Scholar] [CrossRef]
BTX-A Injection in Calf Muscles | |||
---|---|---|---|
Patient Number | Sex | Type of CP | Units/Site and Muscles Injected |
1 | f | unilateral | 50 U, 1 site/muscle belly, gastroc. med. and lat. and soleus right |
3 | m | unilateral | 50 U, 1 site/muscle belly, gastroc. med. and lat. and soleus right |
4 | m | unilateral | 50 U, 1 site/muscle belly, gastroc. med. and lat. and soleus right |
5 | m | bilateral | 75 U, 2 sites/muscle belly, gastroc. med. and lat. and soleus left |
6 | m | bilateral | 100 U, 2 sites/muscle belly, gastroc. med. and lat. left |
7 | m | unilateral | 100 U, 2 sites/muscle belly, gastroc. med. and lat.; 50 U, 1 site, soleus left |
10 | f | unilateral | 100 U, 2 sites/muscle belly, gastroc. med. and lat. and soleus left |
11 | m | unilateral | 75 U, 2 sites/muscle belly, gastroc. med. and lat. right |
12 | m | unilateral | 50 U, 1 site/muscle belly, gastroc. med. and lat. right |
Pre-Btx | ||||||
---|---|---|---|---|---|---|
Spasticity (Modif. Ashworth) (Score) | ROM Dorsiflexion, with Extended Knee (Limiting Muscle) (Degrees) | Manual Muscle Strength Test (MMST) (Score) | ||||
Patient Number | Plantar Flexors, Knee at 90° | Plantar Flexors, Knee at 0° | Gastroc. | Soleus | Plantar Flexors | |
1 | 1 | 1.5 | −10 | −15 | 2.5 | |
3 | 1.5 | 1.5 | −15 | −30 | 2.5 | |
4 | 0 | 1 | −25 | −25 | 2.5 | |
5 | 2 | 3 | −25 | −30 | 3 | |
6 | 1 | 1 | −30 | −20 | 3.5 | |
7 | 1 | 1.5 | 0 | 0 | 2 | |
10 | 0 | 0 | −10 | −15 | 1.5 | |
11 | 1.5 | 1.5 | 5 | 5 | 3 | |
12 | 0 | 0 | 5 | 5 | 2 | |
Mean | 0.9 | 1.2 | −12.0 | −14.0 | 2.5 | |
Stand. Dev. | 0.7 | 0.8 | 11.9 | 12.6 | 0.5 | |
6 Weeks after Btx | ||||||
Spasticity (Modif. Ashworth) (Score) | ROM Dorsiflexion, with Extended Knee (Limiting Muscle) (Degrees) | Manual Muscle Strength Test (MMST) (Score) | ||||
Patient Number | Weeks after Btx | Plantar Flexors, Knee at 90° | Plantar Flexors, Knee at 0° | Gastroc. | Soleus | Plantar Flexors |
1 | 6.9 | 1 | 1 | −10 | −15 | 2.5 |
3 | 6.4 | 1.5 | 1 | −15 | −20 | 2.5 |
4 | 6.3 | 1 | 1 | −20 | −20 | 2.5 |
5 | 5.4 | 2 | 1 | −20 | −25 | 2 |
6 | 5.4 | 1.5 | 1.5 | −20 | −30 | 2.5 |
7 | 5.4 | 0 | 1 | −10 | −15 | 2 |
10 | 6.3 | 0 | 0 | −25 | −25 | 2 |
11 | 5.3 | 1 | 1 | −5 | −5 | 4 |
12 | 6.0 | 1 | 0 | 5 | 0 | 2 |
Mean | 6.0 | 0.9 | 0.8 | −13.0 | −17.0 | 2.5 |
Stand. Dev. | 0.6 | 0.7 | 0.5 | 8.4 | 8.7 | 0.6 |
12 Weeks after Btx | ||||||
Spasticity (Modif. Ashworth) (Score) | ROM Dorsiflexion, with Extended Knee (Limiting Muscle) (Degrees) | Manual Muscle Strength Test (MMST) (Score) | ||||
Patient Number | Weeks after Btx | Plantar Flexors, Knee at 90° | Plantar Flexors, Knee at 0° | Gastroc. | Soleus | Plantar Flexors |
1 | 12.9 | 1 | 1 | −5 | −5 | 3 |
3 | 12.4 | 1 | 1.5 | −20 | −25 | 2.5 |
4 | 12.3 | 1 | 0 | −20 | −25 | 2.5 |
5 | 12.3 | 1 | 1.5 | −20 | −25 | 2.5 |
6 | 11.4 | 1.5 | 0 | −25 | −30 | 2.5 |
7 | 12.0 | 0 | 0 | −10 | −15 | 2 |
10 | 12.4 | 0 | 0 | −20 | −30 | 2 |
11 | 12.3 | 1.5 | 1.5 | 5 | 0 | 4 |
12 | 11.9 | 0 | 0 | −5 | 5 | 2.5 |
Mean | 12.3 | 0.8 | 0.6 | −13.5 | −17.0 | 2.6 |
Stand. Dev. | 0.4 | 0.6 | 0.7 | 9.0 | 12.1 | 0.5 |
Pre-Botox vs. 6 Week F/U | 6 Week F/U vs. 12 Week F/U | Pre-Botox vs. 12 Week F/U | |
---|---|---|---|
Spasticity—PF with 90° kneeflexion | 1 | 0.6193 | 0.6193 |
Spasticity—PF with extended knee | 0.0676 | 0.3951 | 0.03351 |
ROM—DF with 90° kneeflexion and fixed subtalar joint | 0.6681 | 0.8605 | 0.4273 |
ROM—DF with extended knee and fixed subtalar joint | 0.2543 | 1 | 0.3198 |
ROM—DF with extended knee and free subtalar joint | 0.7959 | 0.2795 | 0.4627 |
ROM—KE with extended hip | 0.5716 | 0.7498 | 0.7728 |
Force MMST—PF | 0.8501 | 0.08113 | 0.5911 |
Force MMST—KF | 0.4679 | 0.7103 | 0.1382 |
Patient Number | Treated Leg | Treated Muscles | Total Volume of Treated Muscles [cm³] | Volume of Hyperintense ROI [cm³] | Percentage of Hyperintense Tissue = Relative ROI Size | Total Volume of Triceps Surae [cm³] | Total Triceps Surae Volume of Contralateral Leg [cm³] |
---|---|---|---|---|---|---|---|
1 | r | Gl+Gm+S | 231 | 32.7 | 14% | 231 | 393 |
3 | r | Gl+Gm+S | 225 | 19.6 | 9% | 225 | 361 |
4 | r | Gl+Gm+S | 223 | 32.2 | 14% | 223 | 400 |
5 | l | Gl+Gm+S | 203 | 21.3 | 10% | 203 | 206 |
6 | l | Gl+Gm | 58 | 25.2 | 43% | 124 | 196 |
7 | l | Gl+Gm+S | 249 | 34.8 | 14% | 249 | 354 |
10 | l | Gl+Gm+S | 289 | 31.1 | 11% | 289 | 478 |
11 | r | Gl+Gm | 116 | 11.1 | 10% | 286 | 341 |
12 | r | Gl+Gm | 146 | 22.0 | 15% | 335 | 495 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Brunner, R.; De Pieri, E.; Wyss, C.; Weidensteiner, C.; Bracht-Schweizer, K.; Romkes, J.; Garcia, M.; Ma, N.; Rutz, E. The Non-Affected Muscle Volume Compensates for the Partial Loss of Strength after Injection of Botulinum Toxin A. Toxins 2023, 15, 267. https://doi.org/10.3390/toxins15040267
Brunner R, De Pieri E, Wyss C, Weidensteiner C, Bracht-Schweizer K, Romkes J, Garcia M, Ma N, Rutz E. The Non-Affected Muscle Volume Compensates for the Partial Loss of Strength after Injection of Botulinum Toxin A. Toxins. 2023; 15(4):267. https://doi.org/10.3390/toxins15040267
Chicago/Turabian StyleBrunner, Reinald, Enrico De Pieri, Christian Wyss, Claudia Weidensteiner, Katrin Bracht-Schweizer, Jacqueline Romkes, Meritxell Garcia, Norine Ma, and Erich Rutz. 2023. "The Non-Affected Muscle Volume Compensates for the Partial Loss of Strength after Injection of Botulinum Toxin A" Toxins 15, no. 4: 267. https://doi.org/10.3390/toxins15040267