{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T03:22:54Z","timestamp":1769829774141,"version":"3.49.0"},"reference-count":39,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health with Current Research funds","award":["RAP-2024-0004"],"award-info":[{"award-number":["RAP-2024-0004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Onabotulinum Toxin-A (BTX-A) is a second-line treatment for neurogenic bladder (NB). It requires repeated injections over time, which is a possible limit for long-term adherence, especially in children, as general anesthesia is required. Almost 50% of adults discontinue therapy; few data on pediatric patients are present. The aim of this study is to share our long-term experience of BTX-A adherence in children. This study is a retrospective review of 230 refractory NB patients treated with BTX-A. The inclusion criteria were \u22653 treatments and the first injection performed \u226510 years before the study endpoint. Fifty-four patients were included. Mean follow-up was 10.2 years; mean treatment number was 6.4 for each patient. During follow-up, 7% did not need BTX-A anymore; 76% discontinued therapy, with a prevalence of acquired NB (64% acquired vs. 34% congenital; p = 0.03); sex-based and urodynamic findings did not influence the discontinuation rate (p = 0.6, p = 0.2, respectively). Considering those who withdrew from the therapy, 43% were lost to follow-up\/died after a mean of 7.5 years (although 33% still experienced clinical efficacy); 33% changed therapy after a mean of 5.8 years (with reduced efficacy in 22%, persistent efficacy in 11%). BTX-A is a safe and effective therapy for pediatric patients. The treatment abandonment rate is higher for children than for adults; no specific reasons were highlighted. It is necessary to evaluate any age-specific factors to explain these data.<\/jats:p>","DOI":"10.3390\/toxins16070303","type":"journal-article","created":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T08:17:29Z","timestamp":1719821849000},"page":"303","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Long-Term Adherence to Onabotulinum Toxin-A Intradetrusor Injections for Neurogenic Dysfunction in Children\u2014A Retrospective Single-Center Evaluation"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9813-6288","authenticated-orcid":false,"given":"Chiara","family":"Pellegrino","sequence":"first","affiliation":[{"name":"Division of Neuro-Urology, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza di Sant\u2019Onofrio, 4, 00165 ERN eUROGEN Affiliated Center, 00118 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2233-8777","authenticated-orcid":false,"given":"Valentina","family":"Forlini","sequence":"additional","affiliation":[{"name":"Division of Neuro-Urology, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza di Sant\u2019Onofrio, 4, 00165 ERN eUROGEN Affiliated Center, 00118 Rome, Italy"},{"name":"Pediatric Surgery Division, University of Genova, via Balbi 5, 16126 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Luisa","family":"Capitanucci","sequence":"additional","affiliation":[{"name":"Division of Neuro-Urology, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza di Sant\u2019Onofrio, 4, 00165 ERN eUROGEN Affiliated Center, 00118 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7160-0092","authenticated-orcid":false,"given":"Gessica","family":"Della Bella","sequence":"additional","affiliation":[{"name":"Neurorehabilitation and Adapted Physical Activity Day Hospital, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza di Sant\u2019Onofrio, 4, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9626-9519","authenticated-orcid":false,"given":"Giovanni","family":"Mosiello","sequence":"additional","affiliation":[{"name":"Division of Neuro-Urology, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza di Sant\u2019Onofrio, 4, 00165 ERN eUROGEN Affiliated Center, 00118 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wu, S.Y., Chang, S.J., Yang, S.S., and Hsu, C.K. (2021). Botulinum Toxin Injection for Medically Refractory Neurogenic Bladder in Children: A Systematic Review. Toxins, 13.","DOI":"10.3390\/toxins13070447"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2","DOI":"10.5152\/tud.2019.19070","article-title":"Botulinum toxin therapy in children with neurogenic detrusor overactivity","volume":"46","author":"Badawi","year":"2019","journal-title":"Turk. J. Urol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Pellegrino, C., Forlini, V., Lena, F., Capitanucci, M.L., Diomedi Camassei, F., Castelli, E., and Mosiello, G. (2023). Onabotulinum Toxin A Intradetrusor Injections in Children with Neurogenic Lower Urinary Tract Dysfunction: Long-Term Histological Effects on the Bladder Wall. Biomedicines, 11.","DOI":"10.3390\/biomedicines11051300"},{"key":"ref_4","first-page":"113","article-title":"Agenesia totale del sacro e disfunzione vescicale neurogena [Total agenesis of the sacrum and neurogenic bladder dysfunction]","volume":"19","author":"Capitanucci","year":"1997","journal-title":"Pediatr. Med. Chir."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1046\/j.1464-410X.2003.04326.x","article-title":"Neurovesical dysfunction in children after treating pelvic neoplasms","volume":"92","author":"Mosiello","year":"2003","journal-title":"BJU Int."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1002\/nau.24211","article-title":"EAU\/ESPU guidelines on the management of neurogenic bladder in children and adolescent part I diagnostics and conservative treatment","volume":"39","author":"Stein","year":"2020","journal-title":"Neurourol. Urodyn."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Veenboer, P.W., Bosch, J.L., van Asbeck, F.W., and de Kort, L.M. (2012). Upper and lower urinary tract outcomes in adult myelomeningocele patients: A systematic review. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0048399"},{"key":"ref_8","unstructured":"Radmayr, C., Bogaert, G., Bujons, A., Burgu, B., Castagnetti, M., \u2018t Hoen, L.A., O\u2019Kelly, F., Pakkasj\u00e4rvi, N.A., Quaedackers, J., and Rawashdeh, Y.F.H. (2024). EAU Guidelines. Edn. Presented at the EAU Annual Congress, Paris, France, 5\u20138 April 2024, EAU Guidelines Office."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1046\/j.1464-410x.1998.00810.x","article-title":"Endoscopic treatment for urinary incontinence in children with a congenital neuropathic bladder","volume":"82","author":"Silveri","year":"1998","journal-title":"Br. J. Urol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1007\/BF01349985","article-title":"Occult spinal dysraphism: Neurogenic voiding dysfunction and long-term urologic follow-up","volume":"12","author":"Silveri","year":"1997","journal-title":"Pediatr. Surg. Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1007\/s00383-016-3914-1","article-title":"Anorectal malformations associated spinal cord anomalies","volume":"32","author":"Totonelli","year":"2016","journal-title":"Pediatr. Surg. Int."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1097\/JU.0000000000000540","article-title":"Urodynamic Outcomes in Children after Single and Multiple Injections for Overactive and Low Compliance Neurogenic Bladder Treated with Abobotulinum Toxin A","volume":"203","author":"Naqvi","year":"2020","journal-title":"J. Urol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1002\/nau.23391","article-title":"Adolescence transitional care in neurogenic detrusor overactivity and the use of OnabotulinumtoxinA: A clinical algorithm from an Italian consensus statement","volume":"37","author":"Palleschi","year":"2018","journal-title":"Neurourol. Urodyn."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/j.juro.2018.10.012","article-title":"Long-Term Discontinuation of Botulinum Toxin A Intradetrusor Injections for Neurogenic Detrusor Overactivity: A Multicenter Study","volume":"201","author":"Baron","year":"2019","journal-title":"J. Urol."},{"key":"ref_15","unstructured":"Radmayr, C., Bogaert, G., Burgu, B., Dogan, H., Nijman, J., Quaedackers, J., Rawashdeh, Y., Silay, M., Stein, R., and Tekg\u00fcl, S. (2022). EAU Guidelines. Edn. Presented at the EAU Annual Congress Amsterdam 2022, Amsterdam, The Netherlands, 1\u20134 July 2022, EAU Guidelines Office."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1002\/nau.22934","article-title":"Efficacy and safety of onabotulinumtoxinA therapy are sustained over 4 years of treatment in patients with neurogenic detrusor overactivity: Final results of a long-term extension study","volume":"36","author":"Kennelly","year":"2017","journal-title":"Neurourol. Urodyn."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/j.eururo.2016.03.052","article-title":"More than 15 Years of Experience with Intradetrusor OnabotulinumtoxinA Injections for Treating Refractory Neurogenic Detrusor Overactivity: Lessons to Be Learned","volume":"70","author":"Leitner","year":"2016","journal-title":"Eur. Urol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1002\/nau.22751","article-title":"The standardization of terminology of lower urinary tract function in children and adolescents: Update report from the standardization committee of the International Children\u2019s Continence Society","volume":"35","author":"Austin","year":"2016","journal-title":"Neurourol. Urodyn."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2558","DOI":"10.1016\/j.juro.2011.01.037","article-title":"A simplified technique for botulinum toxin injections in children with neurogenic bladder","volume":"185","author":"Pascali","year":"2011","journal-title":"J. Urol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1080\/00365590600679137","article-title":"Reliability of bladder volume measurement with BladderScan in paediatric patients","volume":"40","author":"Capitanucci","year":"2006","journal-title":"Scand. J. Urol. Nephrol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.jpurol.2013.10.011","article-title":"Single-center experience with botulinum toxin endoscopic detrusor injection for the treatment of congenital neuropathic bladder in children: Effect of dose adjustment, multiple injections, and avoidance of reconstructive procedures","volume":"10","author":"Figueroa","year":"2014","journal-title":"J. Pediatr. Urol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"94.e1","DOI":"10.1016\/j.jpurol.2015.06.019","article-title":"Ten years of experience with intravesical and intrasphincteric onabotulinumtoxinA in children","volume":"12","author":"Greer","year":"2016","journal-title":"J. Pediatr. Urol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1159\/000515991","article-title":"Mechanism and Priority of Botulinum Neurotoxin A versus Sacral Neuromodulation for Refractory Overactive Bladder: A Review","volume":"105","author":"Zhang","year":"2021","journal-title":"Urol. Int."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.jpurol.2018.08.007","article-title":"Onabotulinum toxin A in children with refractory idiopathic overactive bladder: Medium-term outcomes","volume":"15","author":"Ingham","year":"2019","journal-title":"J. Pediatr. Urol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.urology.2018.02.033","article-title":"Intradetrusor Injections of Botulinum Toxin Type A in Children With Spina Bifida: A Multicenter Study","volume":"116","author":"Hascoet","year":"2018","journal-title":"Urology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1002\/nau.23025","article-title":"Outcomes of intra-detrusor injections of botulinum toxin in patients with spina bifida: A systematic review","volume":"36","author":"Hascoet","year":"2017","journal-title":"Neurourol. Urodyn."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.eururo.2008.07.030","article-title":"A minimally invasive approach in the treatment of vesicoureteral reflux in neurogenic bladder in children","volume":"55","author":"Mosiello","year":"2009","journal-title":"Eur. Urol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s00345-016-1847-x","article-title":"Real-life clinical practice of onabotulinum toxin A intravesical injections for overactive bladder wet: An Italian consensus statement","volume":"35","author":"Giannantoni","year":"2017","journal-title":"World J. Urol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1002\/nau.24588","article-title":"OnabotulinumtoxinA for the treatment of neurogenic detrusor overactivity in children","volume":"40","author":"Austin","year":"2021","journal-title":"Neurourol. Urodyn."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1016\/j.purol.2015.07.006","article-title":"D\u00e9finition et prise en charge de l\u2019\u00e9chec d\u2019une premi\u00e8re injection de toxine botulique Botox\u00ae 200 U pour hyperactivit\u00e9 d\u00e9trusorienne neurog\u00e8ne: R\u00e9sultats de l\u2019enqu\u00eate DETOX [Definition of botulinum toxin failure in neurogenic detrusor overactivity: Preliminary results of the DETOX survey]","volume":"25","author":"Peyronnet","year":"2015","journal-title":"Prog. Urol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1002\/nau.25427","article-title":"How to define failure of intradetrusor injections of botulinum toxin A for neurogenic detrusor overactivity","volume":"43","author":"Mailho","year":"2024","journal-title":"Neurourol. Urodyn."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1111\/j.1464-410X.2012.11282.x","article-title":"Long-term outcome of the use of intravesical botulinum toxin for the treatment of overactive bladder (OAB)","volume":"111","author":"Mohee","year":"2013","journal-title":"BJU Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2552","DOI":"10.1016\/j.juro.2011.01.019","article-title":"Effects of botulinum toxin type a in the bladder wall of children with neurogenic bladder dysfunction: A comparison of histological features before and after injections","volume":"185","author":"Pascali","year":"2011","journal-title":"J. Urol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1016\/j.eururo.2006.01.025","article-title":"Histologic features in the urinary bladder wall affected from neurogenic overactivity\u2014A comparison of inflammation, oedema and fibrosis with and without injection of botulinum toxin type A","volume":"50","author":"Reitz","year":"2006","journal-title":"Eur. Urol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1016\/j.eururo.2008.02.037","article-title":"Histological changes in the urothelium and suburothelium of human overactive bladder following intradetrusor injections of botulinum neurotoxin type A for the treatment of neurogenic or idiopathic detrusor overactivity","volume":"53","author":"Apostolidis","year":"2008","journal-title":"Eur. Urol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Bushnell, J.Y., Cates, L.N., Hyde, J.E., Hofstetter, C.P., Yang, C.C., and Khaing, Z.Z. (2022). Early Detrusor Application of Botulinum Toxin A Results in Reduced Bladder Hypertrophy and Fibrosis after Spinal Cord Injury in a Rodent Model. Toxins, 14.","DOI":"10.20944\/preprints202210.0285.v1"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1159\/000064953","article-title":"Clinical features of antibody-induced complete secondary failure of botulinum toxin therapy","volume":"48","author":"Dressler","year":"2002","journal-title":"Eur. Neurol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1002\/nau.23291","article-title":"Switch to Abobotulinum toxin A may be useful in the treatment of neurogenic detrusor overactivity when intradetrusor injections of Onabotulinum toxin A failed","volume":"37","author":"Bottet","year":"2018","journal-title":"Neurourol. Urodyn."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Tiburtius, C., B\u00f6thig, R., Kowald, B., Hirschfeld, S., and Thietje, R. (2020). Can clinical and urodynamic parameters predict the occurrence of neutralizing antibodies in therapy failure of intradetrusor onabotulinumtoxin A injections in patients with spinal cord injury?. BMC Urol., 20.","DOI":"10.1186\/s12894-020-00683-6"}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/16\/7\/303\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:08:41Z","timestamp":1760108921000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/16\/7\/303"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,1]]},"references-count":39,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["toxins16070303"],"URL":"https:\/\/doi.org\/10.3390\/toxins16070303","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,1]]}}}