{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T03:34:46Z","timestamp":1791862486833,"version":"4.3.4"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T00:00:00Z","timestamp":1650844800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T00:00:00Z","timestamp":1650844800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Neurol"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>It is common for people with persistent spasticity due to a stroke to receive an injection of botulinum toxin-A in the upper limb, however post-injection intervention varies.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Aim<\/jats:title>\n                <jats:p>To determine the long-term effect of additional upper limb rehabilitation following botulinum toxin-A in chronic stroke.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Method<\/jats:title>\n                <jats:p>An analysis of long-term outcomes from national, multicenter, Phase III randomised trial with concealed allocation, blinded measurement and intention-to-treat analysis was carried out. Participants were 140 stroke survivors who were scheduled to receive botulinum toxin-A in any muscle(s) that cross the wrist because of moderate to severe spasticity after a stroke greater than 3\u00a0months ago, who had completed formal rehabilitation and had no significant cognitive impairment. Experimental group received botulinum toxin-A plus 3\u00a0months of evidence-based movement training while the control group received botulinum toxin-A plus a handout of exercises. Primary outcomes were goal attainment (Goal Attainment Scale) and upper limb activity (Box and Block Test) at 12\u00a0months (ie, 9\u00a0months beyond the intervention). Secondary outcomes were spasticity, range of motion, strength, pain, burden of care, and health-related quality of life.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>By 12\u00a0months, the experimental group scored the same as the control group on the Goal Attainment Scale (MD 0\u00a0T-score, 95% CI -5 to 5) and on the Box and Block Test (MD 0.01 blocks\/s, 95% CI -0.01 to 0.03). There were no differences between groups on any secondary outcome.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Additional intensive upper limb rehabilitation following botulinum toxin-A in chronic stroke survivors with a disabled upper limb is not more effective in the long-term.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial Registration<\/jats:title>\n                <jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.anzctr.org.au\/Trial\/Registration\/TrialReview.aspx?id=368556&amp;isReview=true\">ACTRN12615000616572<\/jats:ext-link> (12\/06\/2015).\u00a0<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12883-022-02672-8","type":"journal-article","created":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T05:02:58Z","timestamp":1650862978000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Long-term effect of additional rehabilitation following botulinum toxin-A on upper limb activity in chronic stroke: the InTENSE randomised trial"],"prefix":"10.1186","volume":"22","author":[{"given":"Natasha A.","family":"Lannin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Ada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Coralie","family":"English","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Ratcliffe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Faux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mithu","family":"Palit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senen","family":"Gonzalez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Olver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Crotty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian D.","family":"Cameron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,4,25]]},"reference":[{"key":"2672_CR1","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1590\/S0004-282X2005000100006","volume":"63","author":"E Cardoso","year":"2005","unstructured":"Cardoso E, Rodrigues B, Lucena R, de Oliveira IR, Pedreira G, Melo A. Botulinum Toxin Type A for the Treatment of the Upper Limb Spasticity After Stroke. Arq Neuropsiquiatr. 2005;63:30\u20133.","journal-title":"Arq Neuropsiquiatr"},{"issue":"6","key":"2672_CR2","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1177\/0269215515593783","volume":"30","author":"PB Mills","year":"2016","unstructured":"Mills PB, Finlayson H, Sudol M, O\u2019Connor R. Systematic review of adjunct therapies to improve outcomes following botulinum toxin injection for treatment of limb spasticity. Clin Rehabil. 2016;30(6):537\u201348.","journal-title":"Clin Rehabil"},{"issue":"11","key":"2672_CR3","doi-asserted-by":"publisher","first-page":"1569","DOI":"10.2522\/ptj.20130408","volume":"94","author":"BZ Kinnear","year":"2014","unstructured":"Kinnear BZ, Lannin NA, Cusick A, Harvey LA, Rawicki B. Rehabilitation therapies after botulinum toxin-A injection to manage limb spasticity: a systematic review. Phys Ther. 2014;94(11):1569\u201381.","journal-title":"Phys Ther"},{"issue":"5\u20136","key":"2672_CR4","first-page":"453","volume":"25","author":"G Kwakkel","year":"2007","unstructured":"Kwakkel G, Kollen B. Predicting improvement in the upper paretic limb after stroke: a longitudinal prospective study. Restor Neurol Neurosci. 2007;25(5\u20136):453\u201360.","journal-title":"Restor Neurol Neurosci"},{"key":"2672_CR5","doi-asserted-by":"crossref","unstructured":"Cusick A, Lannin, N.A., Kinnear, B. Upper limb spasticity management for patients who have received Botulinum Toxin A injection: Australian therapy practice. Aust Occup Ther J. 2014.","DOI":"10.1111\/1440-1630.12142"},{"key":"2672_CR6","doi-asserted-by":"publisher","first-page":"30","DOI":"10.5348\/D05-2017-28-OA-4","volume":"3","author":"H Scott","year":"2017","unstructured":"Scott H, Lannin NA, English C, Ada L, Levy T, Hart R, Crotty M. Addition of botulinum toxin type A to casting may improve wrist extension in people with chronic stroke and spasticity: A pilot double-blind randomized trial. Edorium J Disabil Rehabil. 2017;3:30\u20135.","journal-title":"Edorium J Disabil Rehabil"},{"issue":"4","key":"2672_CR7","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/S0004-9514(06)70003-4","volume":"52","author":"L Ada","year":"2006","unstructured":"Ada L, Dorsch S, Canning CG. Strengthening interventions increase strength and improve activity after stroke: a systematic review. Aust J Physiother. 2006;52(4):241\u20138.","journal-title":"Aust J Physiother"},{"key":"2672_CR8","doi-asserted-by":"crossref","unstructured":"Shaw L, Rodgers H, Price C, van Wijck F, Shackley P, Steen N, et al. BoTULS: a multicentre randomised controlled trial to evaluate the clinical effectiveness and cost-effectiveness of treating upper limb spasticity due to stroke with botulinum toxin type A. Health Technol Assess. 2010;14(26):1\u2013113, iii-iv.","DOI":"10.3310\/hta14260"},{"issue":"6","key":"2672_CR9","doi-asserted-by":"publisher","first-page":"2123","DOI":"10.1161\/STROKEAHA.108.544585","volume":"40","author":"JE Harris","year":"2009","unstructured":"Harris JE, Eng JJ, Miller WC, Dawson AS. A self-administered Graded Repetitive Arm Supplementary Program (GRASP) improves arm function during inpatient stroke rehabilitation: a multi-site randomized controlled trial. Stroke. 2009;40(6):2123\u20138.","journal-title":"Stroke"},{"key":"2672_CR10","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1161\/STROKEAHA.119.027602","volume":"51","author":"NA Lannin","year":"2020","unstructured":"Lannin NA, Ada L, English C, Ratcliffe J, Faux S, Palit M, Gonzalez S, Olver J, Cameron I. Effect of additional rehabilitation after botulinum toxin-A on upper limb activity in chronic stroke: the InTENSE trial. Stroke. 2020;51:556\u201362.","journal-title":"Stroke"},{"issue":"6","key":"2672_CR11","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1177\/1747493018765228","volume":"13","author":"NA Lannin","year":"2018","unstructured":"Lannin NA, Ada L, English C, Ratcliffe J, Crotty M. Effect of adding intensive upper limb rehabilitation to botulinum toxin-A on upper limb activity after stroke: protocol for the InTENSE trial. Int J Stroke. 2018;13(6):648\u201353.","journal-title":"Int J Stroke"},{"key":"2672_CR12","volume-title":"Position statement on the therapeutic use of botulinum toxin in rehabilitation medicine for spasticity and dystonia","author":"Australasian Faculty of Rehabilitation Medicine","year":"2013","unstructured":"Australasian Faculty of Rehabilitation Medicine. Position statement on the therapeutic use of botulinum toxin in rehabilitation medicine for spasticity and dystonia. Sydney: Australia; 2013."},{"key":"2672_CR13","doi-asserted-by":"crossref","unstructured":"Kiresuk TJ, Smith A, Cardillo JE. Goal Attainment Scaling: Applications, Theory, and Measurement: Taylor & Francis; 2014.","DOI":"10.4324\/9781315801933"},{"issue":"1","key":"2672_CR14","doi-asserted-by":"publisher","first-page":"81","DOI":"10.2340\/16501977-0474","volume":"42","author":"L Turner-Stokes","year":"2010","unstructured":"Turner-Stokes L, Baguley IJ, De Graaff S, Katrak P, Davies L, McCrory P, Hughes A. Goal attainment scaling in the evaluation of treatment of upper limb spasticity with botulinum toxin. J Rehabil Med. 2010;42(1):81\u20139.","journal-title":"J Rehabil Med"},{"issue":"6","key":"2672_CR15","doi-asserted-by":"publisher","first-page":"386","DOI":"10.5014\/ajot.39.6.386","volume":"39","author":"V Mathiowetz","year":"1985","unstructured":"Mathiowetz V, Volland G, Kashman N, Weber K. Adult norms for the Box and Block Test of manual dexterity. Am J Occup Ther. 1985;39(6):386\u201391.","journal-title":"Am J Occup Ther"},{"key":"2672_CR16","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1191\/0269215506cr922oa","volume":"20","author":"E Patrick","year":"2006","unstructured":"Patrick E, Ada L. The Tardieu Scale differentiates contracture from spasticity whereas the Ashworth Scale is confounded by it. Clin Rehabil. 2006;20:173\u201382.","journal-title":"Clin Rehabil"},{"key":"2672_CR17","first-page":"260","volume":"34","author":"L Ada","year":"1988","unstructured":"Ada L, Herbert R. Measurement of joint range of motion. Aust J Physiother. 1988;34:260\u20132.","journal-title":"Aust J Physiother"},{"issue":"4","key":"2672_CR18","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1191\/026921599676433080","volume":"13","author":"P Boissy","year":"1999","unstructured":"Boissy P, Bourbonnais D, Carlotti MM, Gravel D, Arsenault BA. Maximal grip force in chronic stroke subjects and its relationship to global upper extremity function. Clin Rehabil. 1999;13(4):354\u201362.","journal-title":"Clin Rehabil"},{"issue":"2","key":"2672_CR19","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1258\/0007142001903111","volume":"56","author":"BB Bhakta","year":"2000","unstructured":"Bhakta BB. Management of spasticity in stroke. Br Med Bull. 2000;56(2):476\u201385.","journal-title":"Br Med Bull"},{"issue":"6","key":"2672_CR20","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.1007\/s11136-014-0873-7","volume":"24","author":"D Golicki","year":"2015","unstructured":"Golicki D, Niewada M, Karlinska A, et al. Comparing responsiveness of the EQ-5D-5L, EQ-5D-3L and EQ VAS in stroke patients. Qual Life Res. 2015;24(6):1555\u201363.","journal-title":"Qual Life Res"},{"key":"2672_CR21","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1186\/s40814-018-0276-6","volume":"4","author":"NA Lannin","year":"2018","unstructured":"Lannin NA, Ada L, Levy T, English C, Ratcliffe J, Sindhusake D, Crotty M. Intensive therapy after botulinum toxin in adults with spasticity after stroke versus botulinum toxin alone or therapy alone: a feasibility randomised trial. Pilot Feasibility Stud. 2018;4:82.","journal-title":"Pilot Feasibility Stud"},{"issue":"11","key":"2672_CR22","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1002\/acn3.488","volume":"4","author":"CM Stinear","year":"2017","unstructured":"Stinear CM, Byblow WD, Ackerley SJ, Smith MC, Borges VM, Barber PA. PREP2: A biomarker-based algorithm for predicting upper limb function after stroke. Ann Clin Transl Neurol. 2017;4(11):811\u201320.","journal-title":"Ann Clin Transl Neurol"},{"key":"2672_CR23","doi-asserted-by":"publisher","first-page":"2123","DOI":"10.1080\/09638288.2016.1219398","volume":"39","author":"D Intiso","year":"2017","unstructured":"Intiso D, Santamato A, Di Rienzo F. Effect of electrical stimulation as an adjunct to botulinum toxin type A in the treatment of adult spasticity: a systematic review. Disabil Rehabil. 2017;39:2123\u201333.","journal-title":"Disabil Rehabil"},{"key":"2672_CR24","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/j.rehab.2018.08.004","volume":"62","author":"A Picelli","year":"2019","unstructured":"Picelli A, Santamato A, Chemell E, Cinone N, Cisari C, Gandolfi M, Ranieri M, Smania N, Baricich A. Adjuvant treatments associated with botulinum toxin injection for managing spasticity: An overview of the literature. Ann Phys Rehabil Med. 2019;62:291\u20136.","journal-title":"Ann Phys Rehabil Med"},{"key":"2672_CR25","first-page":"87","volume":"23","author":"S Farina","year":"2008","unstructured":"Farina S, Migliorini C, Gandolfi M, Bertolasi L, Casarotto M, Manganotti P. Combined effects of botulinum toxin and casting treatments on lower limb spasticity after stroke. Funct Neurol. 2008;23:87\u201391.","journal-title":"Funct Neurol"},{"key":"2672_CR26","doi-asserted-by":"publisher","first-page":"1703","DOI":"10.1016\/j.apmr.2019.01.016","volume":"100","author":"A Andringa","year":"2019","unstructured":"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\u201325.","journal-title":"Arch Phys Med Rehabil"},{"key":"2672_CR27","doi-asserted-by":"crossref","unstructured":"Sun L-C, Chen R, Fu C, Chen Y, Wu Q, Chen R-P, LinX-J, 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;8329306","DOI":"10.1155\/2019\/8329306"},{"key":"2672_CR28","doi-asserted-by":"publisher","first-page":"104481","DOI":"10.1016\/j.jstrokecerebrovasdis.2019.104481","volume":"29","author":"T Ro","year":"2020","unstructured":"Ro T, Ota T, Saito T, Oikawa O. Spasticity and Range of Motion Over Time in Stroke Patients Who Received Multiple-Dose Botulinum Toxin Therapy. Journal of Stroke and Cerebrovascular Diseases. 2020;29:104481.","journal-title":"Journal of Stroke and Cerebrovascular Diseases"},{"key":"2672_CR29","unstructured":"Stroke Foundation. Clinical guidelines for stroke management. Melbourne: National Health and Medical Research Council; 2017."},{"issue":"6","key":"2672_CR30","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1310\/tsr1606-463","volume":"16","author":"R Teasell","year":"2009","unstructured":"Teasell R, Foley N, Salter K, Bhogal S, Jutai J, Speechley M. Evidence-Based Review of Stroke\u00a0 12th edition\u00a0 Top Stroke Rehabil. 2009;16(6):463\u201388.","journal-title":"Top Stroke Rehabil"},{"key":"2672_CR31","unstructured":"Royal College of Physicians, British Society of Rehabilitation Medicine, The Chartered Society of Physiotherapy, Association of Chartered Physiotherapists in Neurology and the Royal College of Occupational Therapists. Spasticity in adults: management using botulinum toxin. National guidelines. London: RCP, 2018."}],"container-title":["BMC Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12883-022-02672-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12883-022-02672-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12883-022-02672-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T05:05:12Z","timestamp":1650863112000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcneurol.biomedcentral.com\/articles\/10.1186\/s12883-022-02672-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,25]]},"references-count":31,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["2672"],"URL":"https:\/\/doi.org\/10.1186\/s12883-022-02672-8","relation":{},"ISSN":["1471-2377"],"issn-type":[{"value":"1471-2377","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,25]]},"assertion":[{"value":"2 September 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 April 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 April 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The experimental protocol was established, according to the ethical guidelines of the Helsinki Declaration and was approved by the Alfred Health Human Research Ethics Committee on 11 December 2014, reference number 442\/12. Written informed consent was obtained from all study participants and\/or their legal guardian(s) before data collection began. The study was registered in ACTRN on 12 June 2015, reference number ACTRN12615000616572.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"J Olver and S Gonzalez declare that they have received honoraria from Allergan; J Olver, M Palit and S Gonzalez declare that they have received honoraria from Ipsen; S Gonzalez declares that he has received honoraria from Merz. The other authors report no conflicts.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"154"}}