{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T04:24:48Z","timestamp":1771302288033,"version":"3.50.1"},"reference-count":31,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T00:00:00Z","timestamp":1732665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Botulinum toxin type A1 is a first-line treatment for adult and pediatric spasticity. However, when considering the quantity of 150 kDa neurotoxin protein in relation to patient weight and the maximum recommended dose for treating adult and pediatric patients with spasticity, several concerns arise. First, the therapeutic margin (the ratio of the actual maximum quantity of toxin recommended for treating adult spasticity to its median lethal dose) appears to be relevant. Second, there is no consistency between adult and pediatric dosing of botulinum toxin type A1 for spasticity. The third point concerns the suitability of the recommended doses for treating spasticity in pediatric patients. Based on the average body weight of American children and adolescents, the maximum weight-based doses for abobotulinumtoxinA and onabotulinumtoxinA could be administered to children as young as 9 years old. Additionally, the maximum weight-based dose for incobotulinumtoxinA could be administered to children as young as 6 years old. The final point concerns managing the maximum dose of BoNT\/A1 in pediatric patients with spasticity who weigh more than 25 kg for incobotulinumtoxinA, or more than 34 kg for abobotulinumtoxinA and onabotulinumtoxinA. No labeled recommendations are given on the weight cut-off for transitioning to adult dosing in pediatric patients.<\/jats:p>","DOI":"10.3390\/toxins16120513","type":"journal-article","created":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T08:17:42Z","timestamp":1732695462000},"page":"513","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Are We Missing Something About the Maximum Dosing of Botulinum Toxin Type A1 in Adult and Pediatric Patients with Spasticity?"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3558-8276","authenticated-orcid":false,"given":"Alessandro","family":"Picelli","sequence":"first","affiliation":[{"name":"Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy"},{"name":"Department of Neurosciences, University Hospital of Verona, 37126 Verona, Italy"},{"name":"Canadian Advances in Neuro-Orthopedics for Spasticity Consortium (CANOSC), Kingston, ON K7K 1Z6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8017-4013","authenticated-orcid":false,"given":"Rita","family":"Di Censo","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy"},{"name":"Department of Neurosciences, University Hospital of Verona, 37126 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1561-2187","authenticated-orcid":false,"given":"Stefano","family":"Tamburin","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy"},{"name":"Department of Neurosciences, University Hospital of Verona, 37126 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7630-1887","authenticated-orcid":false,"given":"Nicola","family":"Smania","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy"},{"name":"Department of Neurosciences, University Hospital of Verona, 37126 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5930-5974","authenticated-orcid":false,"given":"Mirko","family":"Filippetti","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy"},{"name":"Canadian Advances in Neuro-Orthopedics for Spasticity Consortium (CANOSC), Kingston, ON K7K 1Z6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/nrmicro3295","article-title":"Botulinum neurotoxins: Genetic, structural and mechanistic insights","volume":"12","author":"Rossetto","year":"2014","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1007\/s00204-022-03271-9","article-title":"Toxicology and pharmacology of botulinum and tetanus neurotoxins: An update","volume":"96","author":"Pirazzini","year":"2022","journal-title":"Arch. Toxicol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1124\/pr.116.012658","article-title":"Botulinum neurotoxins: Biology, pharmacology, and toxicology","volume":"69","author":"Pirazzini","year":"2017","journal-title":"Pharmacol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.tox.2013.02.006","article-title":"Botulinum toxins: Mechanisms of action, antinociception and clinical applications","volume":"306","author":"Wheeler","year":"2013","journal-title":"Toxicology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.36849\/JDD.7288","article-title":"The 200-year timeline on botulinum toxin: From biologic poison to wonder drug","volume":"23","author":"Dong","year":"2024","journal-title":"J. Drugs Dermatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"394","DOI":"10.5334\/tohm.321","article-title":"History of botulinum toxin treatment in movement disorders","volume":"6","author":"Jabbari","year":"2016","journal-title":"Tremor. Other Hyperkinet. Mov."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Suputtitada, A., Chatromyen, S., Chen, C.P.C., and Simpson, D.M. (2024). Best practice guidelines for the management of patients with post-stroke spasticity: A modified scoping review. Toxins, 16.","DOI":"10.3390\/toxins16020098"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1818","DOI":"10.1212\/WNL.0000000000002560","article-title":"Practice guideline update summary: Botulinum neurotoxin for the treatment of blepharospasm, cervical dystonia, adult spasticity, and headache: Report of the guideline development subcommittee of the American academy of neurology","volume":"86","author":"Simpson","year":"2016","journal-title":"Neurology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1001\/jama.2010.1937","article-title":"Terminology for preparations of botulinum neurotoxins: What a difference a name makes","volume":"305","author":"Albanese","year":"2011","journal-title":"JAMA"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Brin, M.F., Nelson, M., Ashourian, N., Brideau-Andersen, A., and Maltman, J. (2024). Update on non-interchangeability of botulinum neurotoxin products. Toxins, 16.","DOI":"10.3390\/toxins16060266"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/164_2019_315","article-title":"The use of botulinum toxin for treatment of spasticity","volume":"263","author":"Li","year":"2021","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"13","DOI":"10.2340\/16501977-0303","article-title":"European consensus table on the use of botulinum toxin type A in adult spasticity","volume":"41","author":"Wissel","year":"2009","journal-title":"J. Rehabil. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1177\/15459683211011214","article-title":"A new definition of poststroke spasticity and the interference of spasticity with motor recovery from acute to chronic stages","volume":"35","author":"Li","year":"2021","journal-title":"Neurorehabil Neural Repair."},{"key":"ref_14","unstructured":"(2024, September 11). FDA-Approved Drugs, Available online: www.fda.gov\/drugsatfda."},{"key":"ref_15","unstructured":"(2024, September 11). Agenzia Italiana del Farmaco, Available online: www.aifa.gov.it."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"618","DOI":"10.3111\/13696998.2014.925462","article-title":"Satisfaction with botulinum toxin treatment in post-stroke spasticity: Results from two cross-sectional surveys (patients and physicians)","volume":"17","author":"Bensmail","year":"2014","journal-title":"J. Med. Econ."},{"key":"ref_17","first-page":"85","article-title":"Diffusion of botulinum toxins","volume":"2","author":"Brodsky","year":"2012","journal-title":"Tremor. Other Hyperkinet. Mov."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/S0041-0101(03)00196-X","article-title":"Intramuscular injection of 125I-botulinum neurotoxin-complex versus 125I-botulinum-free neurotoxin: Time course of tissue distribution","volume":"42","author":"Aoki","year":"2003","journal-title":"Toxicon"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Field, M., Splevins, A., Picaut, P., van der Schans, M., Langenberg, J., Noort, D., Snyder, D., and Foster, K. (2018). AbobotulinumtoxinA (Dysport\u00ae), OnabotulinumtoxinA (Botox\u00ae), and IncobotulinumtoxinA (Xeomin\u00ae) neurotoxin content and potential implications for duration of response in patients. Toxins, 10.","DOI":"10.3390\/toxins10120535"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Rossetto, O., and Montecucco, C. (2019). Tables of toxicity of botulinum and tetanus neurotoxins. Toxins, 11.","DOI":"10.3390\/toxins11120686"},{"key":"ref_21","first-page":"3","article-title":"Anthropometric reference data for children and adults: United States, 2015\u20132018. National Center for Health Statistics","volume":"46","author":"Fryar","year":"2021","journal-title":"Vital Health Stat."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Intiso, D., Simone, V., Bartolo, M., Santamato, A., Ranieri, M., Gatta, M.T., and Di Rienzo, F. (2020). High dosage of botulinum toxin type A in adult subjects with spasticity following acquired central nervous system damage: Where are we at?. Toxins, 12.","DOI":"10.3390\/toxins12050315"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Santamato, A. (2022). High doses of botulinum toxin type A for the treatment of post-stroke spasticity: Rationale for a real benefit for the patients. Toxins, 14.","DOI":"10.3390\/toxins14050332"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Intiso, D., Centra, A.M., Gravina, M., Chiaramonte, A., Bartolo, M., and Di Rienzo, F. (2023). Botulinum toxin-A high-dosage effect on functional outcome and spasticity-related pain in subjects with stroke. Toxins, 15.","DOI":"10.3390\/toxins15080509"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1002\/pmrj.12240","article-title":"Adverse event profiles of high dose botulinum toxin injections for spasticity","volume":"12","author":"Kirshblum","year":"2020","journal-title":"PM&R"},{"key":"ref_26","first-page":"1","article-title":"Mean body weight, height, waist circumference, and body mass index among children and adolescents: United States, 1999\u20132018","volume":"160","author":"Fryar","year":"2021","journal-title":"Natl. Health Stat. Rep."},{"key":"ref_27","unstructured":"Mayer, N.Y., and Simpson, D.M. (2005). Botulinum toxin: Historical perspective and potential new indications. Spasticity: Etiology, Evaluation, Management and the Role of Botulinum Toxin, WE MOVE."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1002\/pmrj.12713","article-title":"A consensus statement on the use of botulinum toxin in pediatric patients","volume":"14","author":"Vova","year":"2022","journal-title":"PM&R"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s12325-018-0833-7","article-title":"IncobotulinumtoxinA efficacy and safety in adults with upper-limb spasticity following stroke: Results from the open-label extension period of a phase 3 study","volume":"36","author":"Marciniak","year":"2019","journal-title":"Adv. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1111\/dmcn.13995","article-title":"Systemic adverse events after botulinum neurotoxin A injections in children with cerebral palsy","volume":"60","author":"Paget","year":"2018","journal-title":"Dev. Med. Child. Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s00702-021-02307-1","article-title":"Botulinum toxin dosing in arm muscles: Contextual factors","volume":"128","author":"Dressler","year":"2021","journal-title":"J. Neural Transm."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/16\/12\/513\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:40:19Z","timestamp":1760114419000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/16\/12\/513"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,27]]},"references-count":31,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["toxins16120513"],"URL":"https:\/\/doi.org\/10.3390\/toxins16120513","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,27]]}}}