Effect of Botulinum Toxin Injections in the Treatment of Spasticity of Different Etiologies: An Umbrella Review
Abstract
:1. Introduction
2. Methods
2.1. Search Strategy
2.2. Inclusion and Exclusion Criteria
2.3. Data Extraction
2.4. Methodological Quality Assessment
2.5. Grading the Quality of Evidence
2.6. Data Synthesis
3. Results
3.1. Baseline Characteristics
3.2. Methodological Quality Assessment and GRADE
3.3. Data Synthesis
3.4. Effectiveness of Botulinum Toxin Injection
4. Discussion
4.1. Main Findings
4.2. Interpretation
4.3. Clinical Implications
4.4. Limitations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Gómez-Vega, J.C.; Ocampo-Navia, M.I.; Acevedo-González, J.C. Espasticidad. Univ. Med. 2021, 62, 1. [Google Scholar] [CrossRef]
- Li, S.; Francisco, G.E. The Use of Botulinum Toxin for Treatment of Spasticity. Handb. Exp. Pharmacol. 2021, 263, 127–146. [Google Scholar]
- Howard, I.M.; Patel, A.T. Spasticity evaluation and management tools. Muscle Nerve 2023, 67, 272–283. [Google Scholar] [CrossRef] [PubMed]
- Spasticity. Jhon Hopkins Medicine. Available online: https://www.hopkinsmedicine.org/health/conditions-and-diseases/spasticity (accessed on 4 January 2024).
- Yam, W.K.L.; Leung, M.S.M. Interrater Reliability of Modified Ashworth Scale and Modified Tardieu Scale in Children with Spastic Cerebral Palsy. J. Child Neurol. 2006, 21, 1031–1035. [Google Scholar] [CrossRef] [PubMed]
- Hareb, F.; Bertoncelli, C.M.; Rosello, O.; Rampal, V.; Solla, F. Botulinum Toxin in Children with Cerebral Palsy: An Update. Neuropediatrics 2020, 51, 1–5. [Google Scholar] [CrossRef]
- Ozcakir, S.; Sivrioglu, K. Botulinum toxin in poststroke spasticity. Clin. Med. Res. 2007, 5, 132–138. Available online: https://www.scopus.com/inwards/record.uri?eid=2-s2.0-38949130542&doi=10.3121%2Fcmr.2007.716&partnerID=40&md5=e5cfa8bd4fe44da9aa059bf02eb7ad15 (accessed on 4 January 2024). [CrossRef] [PubMed]
- Varvarousis, D.N.; Martzivanou, C.; Dimopoulos, D.; Dimakopoulos, G.; Vasileiadis, G.I.; Ploumis, A. The effectiveness of botulinum toxin on spasticity and gait of hemiplegic patients after stroke: A systematic review and meta-analysis. Toxicon 2021, 203, 74–84. Available online: https://www.scopus.com/inwards/record.uri?eid=2-s2.0-85116759676&doi=10.1016%2Fj.toxicon.2021.09.020&partnerID=40&md5=aaf19f612382da8660283ad6df767429 (accessed on 5 January 2024). [CrossRef]
- Andringa, A.; van de Port, I.; van Wegen, E.; Ket, J.; Meskers, C.; Kwakkel, G. Effectiveness of Botulinum Toxin Treatment for Upper Limb Spasticity Poststroke Over Different ICF Domains: A Systematic Review and Meta-Analysis. Arch. Phys. Med. Rehabil. 2019, 100, 1703–1725. [Google Scholar] [CrossRef]
- Sun, L.-C.; Chen, R.; Fu, C.; Chen, Y.; Wu, Q.; Chen, R.; Lin, X.; Luo, S. Efficacy and Safety of Botulinum Toxin Type A for Limb Spasticity after Stroke: A Meta-Analysis of Randomized Controlled Trials. Biomed. Res. Int. 2019, 2019, 8329306. [Google Scholar] [CrossRef]
- Dong, Y.; Wu, T.; Hu, X.; Wang, T. Efficacy and safety of botulinum toxin type A for upper limb spasticity after stroke or traumatic brain injury: A systematic review with meta-analysis and trial sequential analysis. Eur. J. Phys. Rehabil. Med. 2017, 53, 256–267. [Google Scholar] [CrossRef]
- Wu, T.; Li, J.H.; Song, H.X.; Dong, Y. Effectiveness of Botulinum Toxin for Lower Limbs Spasticity after Stroke: A Systematic Review and Meta-Analysis. Top. Stroke Rehabil. 2016, 23, 217–223. [Google Scholar] [CrossRef]
- Baker, J.A.; Pereira, G. The efficacy of Botulinum Toxin A for spasticity and pain in adults: A systematic review and meta-analysis using the Grades of Recommendation, Assessment, Development and Evaluation approach. Clin. Rehabil. 2013, 27, 1084–1096. [Google Scholar] [CrossRef]
- Elia, A.E.; Filippini, G.; Calandrella, D.; Albanese, A. Botulinum neurotoxins for poststroke spasticity in adults: A systematic review. Mov. Disord. 2009, 24, 801–812. Available online: https://www.scopus.com/inwards/record.uri?eid=2-s2.0-67651159120&doi=10.1002%2Fmds.22452&partnerID=40&md5=be6e58937f4e53e1d93b40def20038ec (accessed on 5 January 2024). [CrossRef]
- Rosales, R.L.; Chua-Yap, A.S. Evidence-based systematic review on the efficacy and safety of botulinum toxin-A therapy in poststroke spasticity. J. Neural Transm. 2008, 115, 617–623. [Google Scholar] [CrossRef] [PubMed]
- Cardoso, E.; Rodrigues, B.; Lucena, R.; Oliveira, I.R.; Pedreira, G.; Melo, A. Botulinum toxin type a for the treatment of the upper limb spasticity after stroke: A meta-analysis. Arq. Neuro-Psiquiatr. 2005, 63, 30–33. Available online: https://www.cochranelibrary.com/central/doi/10.1002/central/CN-01733102/full (accessed on 5 January 2024). [CrossRef] [PubMed]
- Ojardias, E.; Ollier, E.; Lafaie, L.; Celarier, T.; Giraux, P.; Bertoletti, L. Time course response after single injection of botulinum toxin to treat spasticity after stroke: Systematic review with pharmacodynamic model-based meta-analysis. Ann. Phys. Rehabil. Med. 2022, 5, 101579. [Google Scholar] [CrossRef] [PubMed]
- Guyot, P.; Kalyvas, C.; Mamane, C.; Danchenko, N. Botulinum Toxins Type A (Bont-A) in the Management of Lower Limb Spasticity in Children: A Systematic Literature Review and Bayesian Network Meta-analysis. J. Child. Neurol. 2019, 34, 371–381. [Google Scholar] [CrossRef] [PubMed]
- Blumetti, F.C.; Belloti, J.C.; Tamaoki, M.J.S.; 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, 1465–1858. Available online: https://www.scopus.com/inwards/record.uri?eid=2-s2.0-85081238483&doi=10.1002%2F14651858.CD001408.pub2&partnerID=40&md5=77afa62b48aaa38abb4593c77c67d248 (accessed on 5 January 2024).
- Page, M.J.; McKenzie, J.E.; Bossuyt, P.M.; Boutron, I.; Hoffmann, T.C.; Mulrow, C.D.; Shamseer, L.; Tetzlaff, J.M.; Akl, E.A.; Brennan, S.E.; et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ 2021, 372, 2020–2021. [Google Scholar]
- Higgins, J.P.T.; Green, S. Selecting studies and collecting data. In Cochrane Handbook of Systematic Reviews of Interventions; Version 5.1.0; The Cochrane Collaboration: London, UK, 2011. [Google Scholar]
- Reeuwijk, A.; van Schie, P.E.M.; Becher, J.G.; Kwakkel, G. Effects of botulinum toxin type A on upper limb function in children with cerebral palsy: A systematic review. Clin. Rehabil. 2006, 20, 375–387. [Google Scholar] [CrossRef] [PubMed]
- Demetrios, M.; Khan, F.; Turner-Stokes, L.; Brand, C.; McSweeney, S. Multidisciplinary rehabilitation following botulinum toxin and other focal intramuscular treatment for poststroke spasticity. Cochrane database Syst. Rev. 2013, CD009689. [Google Scholar] [CrossRef]
- Phadke, C.P.; Ismail, F.; Boulias, C.; Gage, W.; Mochizuki, G. The impact of poststroke spasticity and botulinum toxin on standing balance: A systematic review. Expert. Rev. Neurother. 2014, 14, 319–327. [Google Scholar] [CrossRef] [PubMed]
- Garciá Salazar, L.F.; Santos, G.L.D.; Pavaõ, S.L.; Rocha, N.A.C.F.; Russo, T.L.D. Intrinsic properties and functional changes in spastic muscle after application of BTX-A in children with cerebral palsy: Systematic review. Dev. Neurorehabil. 2015, 18, 1–14. Available online: https://www.scopus.com/inwards/record.uri?eid=2-s2.0-84920997967&doi=10.3109%2F17518423.2014.948640&partnerID=40&md5=87218f9e6a1ee5b51a8bf9bc1c9fe04d (accessed on 5 January 2024). [CrossRef] [PubMed]
- Dashtipour, K.; Chen, J.J.; Walker, H.W.; Lee, M.Y. Systematic literature review of abobotulinumtoxinA in clinical trials for adult upper limb spasticity. Am. J. Phys. Med. Rehabil. 2015, 94, 229–238. [Google Scholar] [CrossRef] [PubMed]
- Fonseca, P.R.J.; Calhes Franco de Moura, R.; Galli, M.; Santos Oliveira, C. Effect of physiotherapeutic intervention on the gait after the application of botulinum toxin in children with cerebral palsy: Systematic review. Eur. J. Phys. Rehabil. Med. 2017, 54, 757–765. [Google Scholar] [CrossRef] [PubMed]
- Gupta, A.D.; Chu, W.H.; Howell, S.; Chakraborty, S.; Koblar, S.; Visvanathan, R.; Cameron, I.; Wilson, D. A systematic review: Efficacy of botulinum toxin in walking and quality of life in poststroke lower limb spasticity. Syst. Rev. 2018, 7, 1. [Google Scholar] [CrossRef] [PubMed]
- Yana, M.; Tutuola, F.; Westwater-Wood, S.; Kavlak, E. The efficacy of botulinum toxin A lower limb injections in addition to physiotherapy approaches in children with cerebral palsy: A systematic review. NeuroRehabilitation 2019, 44, 175–189. [Google Scholar] [CrossRef]
- Hara, T.; Momosaki, R.; Niimi, M.; Yamada, N.; Hara, H.; Abo, M. Botulinum Toxin Therapy Combined with Rehabilitation for Stroke: A Systematic Review of Effect on Motor Function. Toxins 2019, 11, 707. [Google Scholar] [CrossRef]
- Farag, S.M.; Mohammed, M.O.; El-Sobky, T.A.; ElKadery, N.A.; ElZohiery, A.K. Botulinum Toxin a Injection in Treatment of Upper Limb Spasticity in Children with Cerebral Palsy: A Systematic Review of Randomized Controlled Trials. JBJS Rev. 2020, 8, e0119. [Google Scholar] [CrossRef]
- Klein, C.; Gouron, R.; Barbier, V. Effects of botulinum toxin injections in the upper limbs of children with cerebral palsy: A systematic review of the literature. Orthop. Traumatol. Surg. Res. 2023, 103578. [Google Scholar] [CrossRef] [PubMed]
- Yang, H.; Chen, S.; Shen, J.; Chen, Y.; Lai, M.; Chen, L.; Fang, S. Safety and Efficacy of Botulinum Toxin Type A in Children with Spastic Cerebral Palsy Aged < 2 Years: A Systematic Review. J. Child. Neurol. 2023, 38, 454–465. [Google Scholar] [PubMed]
- 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. Available online: https://www.scopus.com/inwards/record.uri?eid=2-s2.0-0035502461&doi=10.1046%2Fj.1468-1331.2001.00034.x&partnerID=40&md5=2430a1c0dc0110a9fd929296314ce53e (accessed on 5 January 2024). [CrossRef] [PubMed]
- Wasiak, J.; Hoare, B.; Wallen, M. Botulinum toxin A as an adjunct to treatment in the management of the upper limb in children with spastic cerebral palsy. Cochrane Database Syst. Rev. 2004, CD003469. [Google Scholar] [CrossRef]
- Koog, Y.H.; Min, B.-I. Effects of botulinum toxin A on calf muscles in children with cerebral palsy: A systematic review. Clin. Rehabil. 2010, 24, 685–700. [Google Scholar] [CrossRef] [PubMed]
- Jia, S.; Liu, Y.; Shen, L.; Liang, X.; Xu, X.; Wei, Y. Botulinum Toxin Type A for Upper Limb Spasticity in Poststroke Patients: A Meta-analysis of Randomized Controlled Trials. J. Stroke Cerebrovasc. Dis. Off. J. Natl. Stroke Assoc. 2020, 29, 104682. [Google Scholar] [CrossRef] [PubMed]
- Doan, T.-N.; Kuo, M.-Y.; Chou, L.-W. Efficacy and Optimal Dose of Botulinum Toxin A in Post-Stroke Lower Extremity Spasticity: A Systematic Review and Meta-Analysis. Toxins 2021, 13, 428. [Google Scholar] [CrossRef]
- Shea, B.J.; Reeves, B.C.; Wells, G.; Thuku, M.; Hamel, C.; Moran, J.; Moher, D.; Tugwell, P.; Welch, V.; Kristjansson, E.; et al. AMSTAR 2: A critical appraisal tool for systematic reviews that include randomized or nonrandomized studies of healthcare interventions, or both. BMJ 2017, 358, j4008.23. [Google Scholar] [CrossRef] [PubMed]
- Guyatt, G.H.; Oxman, A.D.; Schünemann, H.J.; Tugwell PKnottnerus, A. GRADE guidelines: A new series of articles in the Journal of Clinical Epidemiology. J. Clin. Epidemiol. 2011, 64, 380–382. [Google Scholar] [CrossRef]
- DerSimonian, R.; Kacker, R. Random-effects model for meta-analysis of clinical trials: An update. Contemp. Clin. Trials. 2007, 28, 105–114. [Google Scholar] [CrossRef]
- Higgins, J.P.T.; Thompson, S.G. Quantifying heterogeneity in a meta-analysis. Stat. Med. 2002, 21, 1539–1558. [Google Scholar] [CrossRef]
- Simon, O.; Yelnik, A. Managing spasticity with drugs. Eur. J. Phys. Rehabil. Med. 2010, 46, 401–410. [Google Scholar]
Reference | Studies Included (n) | Type of Population | Age Range (Years) | Intervention | Comparator | Length (Weeks) | Dossages U/kg/Muscle | Frequency | Injection Site | Spasticity Assessment Scale | Effect | Quality Assessment—AMSTAR 2 |
---|---|---|---|---|---|---|---|---|---|---|---|---|
Reeuwijk, A et al. (2006) [22] | 3 RCT and 9 US | Children with CP | 1.0–18.0 | BOTOX A | Placebo | NR | Botox: 75–300 U Dysport 500–1500 U | NR | Upper limb muscles | MAS | Insufficient evidence | Critically low |
Demetrios, M. et al. (2013) [23] | 3 RCT | Poststroke | NR | BOTOX A | Placebo | 6–24 | 1000 units dysport | NR | Upper limb muscles | MAS | Low-level evidence | Moderate |
Phadke, C.P. et al. (2014) [24] | 5 CT | Poststroke | 16.0–74.0 | BOTOX | NR | 4 | NR | NR | Lower limb and upper limb muscles | MAS Tardieu Scale | Improvement | Moderate |
García Salazar, L.F et al. (2015) [25] | 17 Longitudinal Studies | Children with CP | 2.0–22.0 | BOTOX A | Placebo | 2–24 | NR | NR | Lower limb muscles | MAS Modified Tardieu Scale | Improvement | Moderate |
Dashtipour, K. et al. (2015) [26] | 12 RCT | Poststroke | NR | BOTOX A | Placebo | 2–24 | 500–1500 U | Tree injections | Upper limb muscles | MAS | Safe and effective | Moderate |
Fonseca Junior, P.R. et al. (2017) [27] | 4 RCT | Children with CP | 4.0–14.0 | BOTOX A | NR | 0–26 | 4–25.5 U/kg | Single dose | Lower limb muslces | Modified Tardieu Scale | Effective | Moderate |
Gupta, A.D. et al. (2018) [28] | 5 RCT | Poststroke | 18.0–78.0 | BOTOX A | Placebo | 0–16 | NR | NR | Lower limb muscles | MAS | Effective | Moderate |
Yana, M. et al. (2019) [29] | 4 RCT | Children with CP | 2.0–8.0 | BOTOX A | NR | 8–48 | 100–500 U/muscle | 6–8 injections | Lower limb muscles | MAS | Positive improvement | Moderate |
Hara, T. et al. (2019) [30] | 24 RCT and 2 comparative studies | Poststroke | 41.2–67.0 | BOTOX A | Placebo | 1–27 | 500–1000 U | Multiple doses | Upper and lower limb muscles | MAS | Limited effectiveness | Moderate |
Farag, S.M. et al. (2020) [31] | 15 RCT | Children with CP | 2.6–10.7 | BOTOX A | Placebo | 2–27 | 160–1000 U | Repeated sesions | Upper limb muscles | MAS Tardieu Scale | Improvement | Moderate |
Klein, C. et al. (2023) [32] | 24 RCT | Children with CP | 3 y 1 mo–10 y | BOTOX A | Placebo | 0–26 | 2–16 U/kg | NR | Upper limb muscles | MAS Tardieu Scale | Improvement | Moderate |
Yang, H. et al. (2023) [33] | 12 RCT | Children with CP | 8 mo–10 y | BOTOX A | NR | 0–24 | 0.5–20 U/kg | Single injection 6 months | Lower limb muscles | MAS Modified Tardieu Scale | Safety and efficacy | Moderate |
Reference | Study Design | Studies Included (n) | Type of Population | Age Range (Years) | Intervention | Comparator | Length (Weeks) | Dosages | Frequency | Injection Site | Spasticity Assessment Scale | Effect SMD (95% CI) | Quality Assessment—AMSTAR 2 |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Boyd, R. and Hays, R. (2001) [34] | SR and meta-analysis | 10 RCT | Children with CP | 2.0–13.0 | BOTOX A | Placebo | 6–24 | 2–25.5 U/kg/muscle | 4 weeks | Lower limb muscles | MAS | NR | Critically low |
Wasiak, J. et al. (2004) [35] | SR and meta-analysis | 2 RCT | Children with CP | 2.5–10.0 | BOTOX A | Placebo | 2–12 | 2–9 U/kg/muscle | NR | Upper limb muscles | Tardieu Scale MAS | MAS −0.04 (−0.14, 0.05) | Low |
Cardoso, E. et al. (2005) [16] | SR and meta-analysis | 5 RCT | Poststroke | NR | BOTOX A | Placebo | 4–6 | NR | NR | Lower limb muscles | MAS | MAS −0.95 (−1.17, −0.74) | Low |
Rosales, R. et al. (2008) [15] | SR and meta-analysis | 9 RCT | Poststroke | NR | BOTOX A | Placebo | 4–6 | 500–1500 U dysport 200–360 U Botox | NR | Upper limb muscles | MAS | MAS −0.87 (−1.22, −0.52) | Moderate |
Elia, A.E. et al. (2009) [14] | SR and meta-analysis | 11 RCT | Poststroke | NR | BOTOX A BOTOX B | Placebo | 3–6 9–12 | 10–3750 U/muscle | Regular intervals | Upper limb muscles | MAS | MAS −0.98 (−1.17, −0.78) | High |
Koog, Y.H. and Min, B.I. (2010) [36] | SR and meta-analysis | 15 RCT | Children with CP | <12.0 | Botox, HengLi, and Dysport | NR | 4–16 | 2.8–30 U/kg | NR | Lower limb muscles | MAS | High | |
Baker, J.A. and Pereira, G. (2013) [13] | SR and meta-analysis | 37 RCT | Adults with spasticity | NR | BOTOX A | Placebo | 4–12 | NR | Single dose | Upper limb and lower limb muscles | MAS Modified Tardieu Scale | MAS −0.88 (−1.14, −0.63) | Moderate |
Wu, T. et al. (2016) [12] | SR and meta-analysis | 7 RCT | Poststroke | 14.0–85.0 | BOTOX | Placebo | 8–24 | 100–400 U | NR | Lower limb muscles | MAS | MAS −0.66 (−1.11, −0.22) | High |
Dong, Y. et al. (2017) [11] | SR and meta-analysis | 22 RCT | Poststroke | 57.6 | BOTOX A | Placebo | 2–24 | 80–1500 U | NR | Lower limb muscles | MAS Tardieu Scale | MAS −0.81 (−0.93, −0.68) | High |
Guyot, P. et al. (2019) [18] | SR and network meta-analysis | 10 RCT | Children with spasticity | 1.7–7.4 | BOTOX A | Placebo | 4–12 | 0.5–30 U/kg/leg | NR | Lower limb muscles | MAS Tardieu Scale | MAS −0.1 (−0.3, 0.1) | High |
Blumetti, F.C. et al. (2019) [19] | SR and meta-analysis | 31 RCT in SR 28 RCT in meta-analysis | Children with CP | 1.3–9.5 | BOTOX A | Placebo | 2–48 | 4–30 U/kg | 3–6 months 2–4 weeks | Lower limb muscles | MAS Modified Tardieu Scale | Modified Tardiue Scale. −0.83 (−0.98, −0.67) MAS −0.42 (−0.65, −0.18) | High |
Sun, L.C. et al. (2019) [10] | SR and meta-analysis | 27 RCT | Poststroke | 49.3–63.5 | BOTOX A | Placebo | 4–24 | 75–1500 U | NR | Upper limb and lower limb muscles | MAS | MAS −0.76 (−0.97, −0.55) | High |
Jia, S. et al. (2020) [37] | SR and meta-analysis | 10 RCT | Poststroke | 18.0–92.0 | BOTOX A | Placebo | 12–24 | 75–1500 U | NR | Upper limb muscles | MAS | MAS −0.33 (−0.54, −0.12) | High |
Doan, T.N. et al. (2021) [38] | SR and meta-analysis | 12 RCT | Poststroke | NR | BOTOX A | Placebo | NR | Botox: 100–540 U Dysport: 500–1500 U | NR | Lower limb muscles | MAS | MAS −0.45 (−0.73, −0.18) | High |
Varvarousis, D.N. et al. (2021) [8] | SR and meta-analysis | 21 CCT and RCT | Poststroke | NR | BOTOX A | NR | NR | <200 U, >200 U | NR | Upper limb and lower limb muscles | MAS | NR | High |
Ojardias, E. et al. (2022) [17] | SR and meta-analysis | 37 RCT | Poststroke | 52.0–67.0 | BOTOX A | Placebo | NR | NR | Single injection 00 | Upper limb muscles | MAS | MAS −0.11 (−0.18, −0.04) | High |
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. |
© 2024 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
Otero-Luis, I.; Martinez-Rodrigo, A.; Cavero-Redondo, I.; Moreno-Herráiz, N.; Martínez-García, I.; Saz-Lara, A. Effect of Botulinum Toxin Injections in the Treatment of Spasticity of Different Etiologies: An Umbrella Review. Pharmaceuticals 2024, 17, 310. https://doi.org/10.3390/ph17030310
Otero-Luis I, Martinez-Rodrigo A, Cavero-Redondo I, Moreno-Herráiz N, Martínez-García I, Saz-Lara A. Effect of Botulinum Toxin Injections in the Treatment of Spasticity of Different Etiologies: An Umbrella Review. Pharmaceuticals. 2024; 17(3):310. https://doi.org/10.3390/ph17030310
Chicago/Turabian StyleOtero-Luis, Iris, Arturo Martinez-Rodrigo, Iván Cavero-Redondo, Nerea Moreno-Herráiz, Irene Martínez-García, and Alicia Saz-Lara. 2024. "Effect of Botulinum Toxin Injections in the Treatment of Spasticity of Different Etiologies: An Umbrella Review" Pharmaceuticals 17, no. 3: 310. https://doi.org/10.3390/ph17030310
APA StyleOtero-Luis, I., Martinez-Rodrigo, A., Cavero-Redondo, I., Moreno-Herráiz, N., Martínez-García, I., & Saz-Lara, A. (2024). Effect of Botulinum Toxin Injections in the Treatment of Spasticity of Different Etiologies: An Umbrella Review. Pharmaceuticals, 17(3), 310. https://doi.org/10.3390/ph17030310