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Abstract
Introduction: Facial paralysis causes functional, aesthetic, and psychosocial limitations that affect quality of life. Botulinum toxin type A (BoNT-A) is used as a therapeutic strategy; however, the evidence supporting its effectiveness and safety is heterogeneous and of variable quality. This systematic review and meta-research analysis aimed to synthesize the available evidence and assess the methodological and reporting quality of randomized controlled trials (RCTs) in this field. Methods: Searches were conducted in PubMed, Scopus, and Web of Science through June 2025. RCTs evaluating BoNT-A in patients with facial paralysis of any etiology were included. Data extraction was performed independently and in duplicate. Risk of bias was assessed using the Cochrane RoB 2.0 tool, methodological quality with the Joanna Briggs Institute checklist for RCTs, and reporting quality with the CONSORT 2025 guidelines. Results: Six RCTs (n = 262 patients) met the inclusion criteria. BoNT-A demonstrated consistent benefits in facial symmetry, reduction of synkinesis, and functional improvement compared with conservative treatment, placebo, or no treatment. The safety profile was favorable, with mild and transient adverse events. However, several studies showed limitations in randomization, blinding, and selective outcome reporting, which restricted the overall certainty of the evidence. Conclusion: BoNT-A appears to be a promising and safe intervention for facial paralysis. Nevertheless, the current evidence remains limited in both number and quality, underscoring the need for future, better-designed and more rigorously reported trials to establish robust clinical recommendations.
References
Walker NR, Mistry RK, Mazzoni T. Facial Nerve Palsy. [Updated 2023 Jul 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK549815/
Ottavi A, Cozzi A, Allevi F, Calvo-Henriquez C, Chiesa-Estomba C, Felisati G, et al. Therapeutic management of traumatic facial palsy: a systematic review. Eur Arch Otorhinolaryngol. 2025 Sep;282(9):4443-4454. doi: 10.1007/s00405-025-09367-z.
Khan AJ, Szczepura A, Palmer S, Bark C, Neville C, Thomson D, et al. Physical therapy for facial nerve paralysis (Bell's palsy): An updated and extended systematic review of the evidence for facial exercise therapy. Clin Rehabil. 2022 Nov;36(11):1424-1449. doi: 10.1177/02692155221110727
de Sanctis Pecora C, Shitara D. Botulinum Toxin Type A to Improve Facial Symmetry in Facial Palsy: A Practical Guideline and Clinical Experience. Toxins (Basel). 2021 Feb 18;13(2):159. doi: 10.3390/toxins13020159
Salles AG, Mota WM, Remigio AFDN, de Andrade ACH, Gemperli R. Management of Post-Facelift Facial Paralysis With Botulinum Toxin Type A. Aesthet Surg J. 2022 Feb 15;42(3):NP144-NP150. doi: 10.1093/asj/sjab311
de Jongh FW, Schaeffers AWMA, Kooreman ZE, Ingels KJAO, van Heerbeek N, Beurskens C, et al. Botulinum toxin A treatment in facial palsy synkinesis: a systematic review and meta-analysis. Eur Arch Otorhinolaryngol. 2023 Apr;280(4):1581-1592. doi: 10.1007/s00405-022-07796-8
Fuzi J, Taylor A, Sideris A, Meller C. Does Botulinum Toxin Therapy Improve Quality of Life in Patients with Facial Palsy? Aesthetic Plast Surg. 2020 Oct;44(5):1811-1819. doi: 10.1007/s00266-020-01870-4
Blanco-Teherán C, Quintana-Pájaro L, Narvaez-Rojas A, Martínez-Pérez R, García-Ballestas E, Moscote Salazar L, et al. Evidence-based medicine in neurosurgery: why and how? J Neurosurg Sci. 2022 Feb;66(1):49-53. doi: 10.23736/S0390-5616.21.05331-5
Ortega-Sierra MG, Charry-Caicedo JI, Orrego-Torres AT, Rueda-Ibarra L, Lozada Martínez ID. Breaking down barriers to surgical learning in times of COVID-19: an initiative of future surgeons. Eur Surg. 2021;53(5):259-260. doi: 10.1007/s10353-021-00723-x
Lozada-Martínez ID, Acevedo-Aguilar LM, Mass-Hernández LM, Matta-Rodríguez D, Jiménez-Filigrana JA, Garzón-Gutiérrez KE, et al. Practical guide for the use of medical evidence in scientific publication: Recommendations for the medical student: Narrative review. Ann Med Surg (Lond). 2021 Oct 9;71:102932. doi: 10.1016/j.amsu.2021.102932
Lozada-Martinez ID, Hernandez-Paez D, Zárate YEJ, Delgado P. Scientometrics and meta-research in medical research: approaches required to ensure scientific rigor in an era of massive low-quality research. Rev Assoc Med Bras (1992). 2025 Jun 6;71(4):e20241612. doi: 10.1590/1806-9282.20241612
Lozada-Martinez ID, Hernandez-Paz DA, Fiorillo-Moreno O, Picón-Jaimes YA, Bermúdez V. Meta-Research in Biomedical Investigation: Gaps and Opportunities Based on Meta-Research Publications and Global Indicators in Health, Science, and Human Development. Publications. 2025; 13(1):7. doi: 10.3390/publications13010007
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021 Mar 29;372:n71. doi: 10.1136/bmj.n71
Lozada-Martinez ID, Diazgranados-Garcia MC, Castelblanco-Toro S, Anaya JM. Global Research on Centenarians: A Historical and Comprehensive Bibliometric Analysis from 1887 to 2023. Ann Geriatr Med Res. 2024 Jun;28(2):144-155. doi: 10.4235/agmr.24.0043
Revolledo Caicedo MA, Montoya Obando AF, Hernández-Páez DA, Fiorillo-Moreno O, Galván-Barrios J, Delgado P, et al. Research on medical errors exhibits diverse associations with global indicators of science, development, and health across geographic regions: A scientometrics study. Medicine (Baltimore). 2025 Jul 18;104(29):e42985. doi: 10.1097/MD.0000000000042985
Angarita-Pacheco Y, Urbano López AD, Hernandez-Paez DA, Fiorillo-Moreno O, Picón-Jaimes YA, Beltrán Venegas T, et al. Global Trends and Evidence Gaps in Medical Errors Research: A Mixed-Methods Scientometrics Study. J Multidiscip Healthc. 2025 May 3;18:2497-2508. doi: 10.2147/JMDH.S516383
Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan-a web and mobile app for systematic reviews. Syst Rev. 2016 Dec 5;5(1):210. doi: 10.1186/s13643-016-0384-4
Sterne JAC, Savovic J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019 Aug 28;366:l4898. doi: 10.1136/bmj.l4898
Barker TH, Stone JC, Sears K, Klugar M, Tufanaru C, Leonardi-Bee J, et al. The revised JBI critical appraisal tool for the assessment of risk of bias for randomized controlled trials. JBI Evid Synth. 2023 Mar 1;21(3):494-506. doi: 10.11124/JBIES-22-00430
Hopewell S, Chan AW, Collins GS, Hróbjartsson A, Moher D, Schulz KF, et al. CONSORT 2025 statement: updated guideline for reporting randomised trials. Lancet. 2025 Apr 14:S0140-6736(25)00672-5. doi: 10.1016/S0140-6736(25)00672-5
Akulov MA, Orlova OR, Orlova AS, Usachev DJ, Shimansky VN, Tanjashin SV, et al. IncobotulinumtoxinA treatment of facial nerve palsy after neurosurgery. J Neurol Sci. 2017 Oct 15;381:130-134. doi: 10.1016/j.jns.2017.08.3244
Akulov MA, Tanyashin SV, Usachev DY, Shimanskiy VN, Orlova OR, Zakharov VO, et al. Botulinum Toxin a Treatment of Delayed Facial Palsy in a Randomized Trial. Ser J Exp Clin Res. 2021; 22(2):137-144.
D'Andrea FP, Alessi C, Cárcano C, Tanaka V, Alvares B, Brito D, et al. Evaluation of the Efficacy of the Combined Therapy of Botulinum Toxin and Hyaluronic Acid Compared to Conservative Intervention in the Treatment of Chronic Peripheral Facial Paralysis of Oncologic Etiology. Aesthetic Plast Surg. 2025 Jun;49(11):2861-2870. doi: 10.1007/s00266-024-04589-8
do Nascimento Remigio AF, Salles AG, de Faria JCM, Ferreira MC. Comparison of the efficacy of onabotulinumtoxinA and abobotulinumtoxinA at the 1: 3 conversion ratio for the treatment of asymmetry after long-term facial paralysis. Plast Reconstr Surg. 2015 Jan;135(1):239-249. doi: 10.1097/PRS.0000000000000800
Pourmomeny AA, Asadi S, Cheatsaz A. Management of Facial Synkinesis with a Combination of BTX-A and Biofeedback: A Randomized Trial. Iran J Otorhinolaryngol. 2015 Nov;27(83):409-15
Pourmomeny AA, Pourali E, Chitsaz A. Neuromuscular Retraining versus BTX-A Injection in Subjects with Chronic Facial Nerve Palsy, A Clinical Trial. Iran J Otorhinolaryngol. 2021 May;33(116):151-155. doi: 10.22038/ijorl.2021.41305.2347
Carré F, Amar J, Tankéré F, Foirest C. Botulinum Toxin Injections to Manage Sequelae of Peripheral Facial Palsy. Toxins (Basel). 2024 Mar 20;16(3):161. doi: 10.3390/toxins16030161
Moosapour H, Saeidifard F, Aalaa M, Soltani A, Larijani B. The rationale behind systematic reviews in clinical medicine: a conceptual framework. J Diabetes Metab Disord. 2021 Apr 8;20(1):919-929. doi: 10.1007/s40200-021-00773-8
Brignardello-Petersen R, Santesso N, Guyatt GH. Systematic reviews of the literature: an introduction to current methods. Am J Epidemiol. 2025 Feb 5;194(2):536-542. doi: 10.1093/aje/kwae232
Lozada-Martinez ID, Fiorillo-Moreno O, Hernández-Paez DA, Bermúdez V. Clinical trials on medical errors need to strengthen geographical representation, methodological and reporting quality. QJM. 2025 Mar 12:hcaf068. doi: 10.1093/qjmed/hcaf068
Lozada-Martinez ID, Neira-Rodado D, Martinez-Guevara D, Cruz-Soto HS, Sanchez-Echeverry MP, Liscano Y. Why is it important to implement meta-research in universities and institutes with medical research activities? Front Res Metr Anal. 2025 Mar 19;10:1497280. doi: 10.3389/frma.2025.1497280
Ioannidis JPA. Meta-research: Why research on research matters. PLoS Biol. 2018 Mar 13;16(3):e2005468. doi: 10.1371/journal.pbio.2005468
Stevens ER, Laynor G. Recognizing the value of meta-research and making it easier to find. J Med Libr Assoc. 2023 Oct 2;111(4):839-843. doi: 10.5195/jmla.2023.1758
Luchini C, Veronese N, Nottegar A, Shin JI, Gentile G, Granziol U, et al. Assessing the quality of studies in meta-research: Review/guidelines on the most important quality assessment tools. Pharm Stat. 2021 Jan;20(1):185-195. doi: 10.1002/pst.2068
Lassaletta L, Morales-Puebla JM, Altuna X, Arbizu Á, Arístegui M, Batuecas Á, et al. Facial paralysis: Clinical practice guideline of the Spanish Society of Otolaryngology. Acta Otorrinolaringol Esp (Engl Ed). 2020 Mar-Apr;71(2):99-118. English, Spanish. doi: 10.1016/j.otorri.2018.12.004
Lozada-Martínez I, Bolaño-Romero M, Moscote-Salazar L, Torres-Llinas D. Letter to the Editor: 'Medical Education in Times of COVID-19: What's New in Neurosurgery?'. World Neurosurg. 2020 Nov;143:603.
Maiguel-Lapeira J, Lozada-Martinez I, Torres-Llinás D, Moscote-Salazar LR, Al-Dhahir M. Letter to the Editor. Academic and research interest groups in neurosurgery: a smart strategy in times of COVID-19. J Neurosurg. 2021 Mar 26;135(2):668-669
Ortega-Sierra MG, Beltran-Hoyos GE, Benjumea-Velásquez AM, Bossio-Martínez IM, Lozada-Martínez ID. Letter Regarding: Surgery Interest Groups in Medical Schools: Mentoring Factory. J Surg Res. 2021 Nov;267:209-210
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Copyright (c) 2026 Lucia Tatiana Romero Pineda, Isabella Vejarano Vega, Camilo Andrés Carbonell Melendrez, Ana Lucía Ordóñez Guerrero, Matías Díaz Perdomo, Camilo Villa González, Melissa Orozco Gallego, Miguel Ángel Bermúdez Lozano, Daniela García Pereira, Michael Ortega Sierra