{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T10:19:47Z","timestamp":1783937987260,"version":"3.55.0"},"reference-count":80,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,5,10]],"date-time":"2020-05-10T00:00:00Z","timestamp":1589068800000},"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>Spasticity is a common disabling disorder in adult subjects suffering from stroke, brain injury, multiple sclerosis (MS) and spinal cord injury (SCI). Spasticity may be a disabling symptom in people during rehabilitation and botulinum toxin type A (BTX-A) has become the first-line therapy for the local form. High BTX-A doses are often used in clinical practice. Advantages and limitations are debated and the evidence is unclear. Therefore, we analysed the efficacy, safety and evidence for BTX-A high doses. Studies published from January 1989 to February 2020 were retrieved from MEDLINE\/PubMed, Embase, Cochrane Central Register. Only obabotulinumtoxinA (obaBTX-A), onabotulinumtoxinA (onaBTX-A), and incobotulinumtoxinA (incoBTX-A) were considered. The term \u201chigh dosage\u201d indicated \u2265 600 U. Thirteen studies met the inclusion criteria. Studies had variable method designs, sample sizes and aims, with only two randomised controlled trials. IncoBTX-A and onaBTX-A were injected in three and eight studies, respectively. BTX-A high doses were used predominantly in treating post-stroke spasticity. No studies were retrieved regarding treating spasticity in MS and SCI. Dosage of BTX-A up to 840 U resulted efficacious and safety without no serious adverse events (AEs). Evidence is insufficient to recommend high BTX-A use in clinical practice, but in selected patients, the benefits of high dose BTX-A may be clinically acceptable.<\/jats:p>","DOI":"10.3390\/toxins12050315","type":"journal-article","created":{"date-parts":[[2020,5,12]],"date-time":"2020-05-12T02:41:20Z","timestamp":1589251280000},"page":"315","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["High Dosage of Botulinum Toxin Type A in Adult Subjects with Spasticity Following Acquired Central Nervous System Damage: Where Are We at?"],"prefix":"10.3390","volume":"12","author":[{"given":"Domenico","family":"Intiso","sequence":"first","affiliation":[{"name":"Unit of Neuro-Rehabilitation Unit and Rehabilitation Medicine, IRCCS \u2018Casa Sollievo della Sofferenza\u2019, Viale dei Cappuccini 1, San Giovanni Rotondo, 71013 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Simone","sequence":"additional","affiliation":[{"name":"Unit of Neuro-Rehabilitation Unit and Rehabilitation Medicine, IRCCS \u2018Casa Sollievo della Sofferenza\u2019, Viale dei Cappuccini 1, San Giovanni Rotondo, 71013 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelangelo","family":"Bartolo","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, Neurorehabilitation Unit, HABILITA Zingonia, Ciserano, 24040 Bergamo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1452-8485","authenticated-orcid":false,"given":"Andrea","family":"Santamato","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, OO.RR Hospital, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Ranieri","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, OO.RR Hospital, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Teresa","family":"Gatta","sequence":"additional","affiliation":[{"name":"Unit of Neuro-Rehabilitation Unit and Rehabilitation Medicine, IRCCS \u2018Casa Sollievo della Sofferenza\u2019, Viale dei Cappuccini 1, San Giovanni Rotondo, 71013 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filomena","family":"Di Rienzo","sequence":"additional","affiliation":[{"name":"Unit of Neuro-Rehabilitation Unit and Rehabilitation Medicine, IRCCS \u2018Casa Sollievo della Sofferenza\u2019, Viale dei Cappuccini 1, San Giovanni Rotondo, 71013 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,10]]},"reference":[{"key":"ref_1","unstructured":"Feldman, R.G., Young, R.R., and Koella, W.P. 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