{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:15:06Z","timestamp":1790014506619,"version":"4.0.1"},"reference-count":80,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ERA-NET NEURON under the European Research Projects on Neurodegenerative Diseases (NEURON) funding scheme","award":["964215"],"award-info":[{"award-number":["964215"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Background: Botulinum toxin type A (BoNT-A) is globally recognized as a standard treatment for post-stroke spasticity (PSS), although its secondary mechanisms remain underinvestigated. The objective of this study was to investigate the neurophysiological mechanisms underlying BoNT-A treatment in PSS and explore their implications for mechanism-based rehabilitation. Methods: A systematic review and meta-analysis (PROSPERO registration number ID: CRD420261352230) of 39 studies involving 760 patients was conducted on 18 August 2026, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Web of Science, Scopus, and Embase were systematically searched using the PICO framework. Where possible, quantitative data were pooled according to predefined neurophysiological constructs, including passive stretch-evoked activity, voluntary activation of the injected muscle, compound muscle action potential (CMAP), reciprocal motor control, normalized Hmax\/Mmax, and specific spinal inhibitory mechanisms. Results: Quantitative synthesis demonstrated construct-specific neurophysiological changes following BoNT-A treatment. Passive stretch-evoked activity showed the largest pooled effect (Hedges\u2019 g = 0.80, 95% CI 0.35\u20131.24), followed by CMAP amplitude (g = 0.69, 95% CI 0.23\u20131.14) and reciprocal motor control (g = 0.52, 95% CI 0.23\u20130.81). Effects on voluntary activation of the injected muscle (g = 0.31, 95% CI \u22120.38 to 1.00) and normalized Hmax\/Mmax (g = 0.22, 95% CI \u22120.74 to 1.17) were smaller and more heterogeneous. Reciprocal and recurrent inhibition were each represented by single-study estimates, while supraspinal outcomes were synthesized narratively due to methodological heterogeneity. Conclusions: The findings support a predominantly peripheral mechanism of BoNT-A while suggesting possible secondary changes within spinal and supraspinal motor control pathways. However, the certainty of evidence was low to very low. These neurophysiological effects provide a rationale for individualized, mechanism-based rehabilitation during the post-injection therapeutic window, although higher-quality evidence is required to confirm this framework.<\/jats:p>","DOI":"10.3390\/toxins18090402","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:23:17Z","timestamp":1790011397000},"page":"402","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["From Neurophysiological Mechanisms to Rehabilitation After Botulinum Toxin Type A in Post-Stroke Spasticity"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-2126-1782","authenticated-orcid":false,"given":"Bart","family":"Eeckhaut","sequence":"first","affiliation":[{"name":"Department of Rehabilitation Sciences and Physiotherapy, Faculty of Medicine and Health Sciences, University of Antwerp, Universiteitsplein 1, 2610 Antwerpen, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0604-1431","authenticated-orcid":false,"given":"Steven","family":"Truijen","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Sciences and Physiotherapy, Faculty of Medicine and Health Sciences, University of Antwerp, Universiteitsplein 1, 2610 Antwerpen, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parham","family":"Haghshenas","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Sciences and Physiotherapy, Faculty of Medicine and Health Sciences, University of Antwerp, Universiteitsplein 1, 2610 Antwerpen, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3901-9508","authenticated-orcid":false,"given":"Antriana","family":"Roussou","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Sciences and Physiotherapy, Faculty of Medicine and Health Sciences, University of Antwerp, Universiteitsplein 1, 2610 Antwerpen, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petros","family":"Taflampas","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Sciences and Physiotherapy, Faculty of Medicine and Health Sciences, University of Antwerp, Universiteitsplein 1, 2610 Antwerpen, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8193-5016","authenticated-orcid":false,"given":"Wim","family":"Saeys","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Sciences and Physiotherapy, Faculty of Medicine and Health Sciences, University of Antwerp, Universiteitsplein 1, 2610 Antwerpen, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.1161\/STR.0b013e318296aeca","article-title":"An updated definition of stroke for the 21st century: A statement for healthcare professionals from the American Heart Association\/American Stroke Association","volume":"44","author":"Sacco","year":"2013","journal-title":"Stroke"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"313","DOI":"10.5014\/ajot.43.5.313","article-title":"Weakness in patients with Hemiparesis","volume":"43","author":"Bourbonnais","year":"1989","journal-title":"Am. J. Occup. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Santello, M., and Lang, C.E. (2015). Are movement disorders and sensorimotor injuries pathologic synergies? When normal multi-joint movement synergies become pathologic. Front. Hum. Neurosci., 8.","DOI":"10.3389\/fnhum.2014.01050"},{"key":"ref_4","unstructured":"Lance, J.W. (1980). Spasticity: Disorder of Motor Control, Year Book Medical Publishers."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1080\/09638280400014576","article-title":"Spasticity: Clinical perceptions, neurological realities and meaningful measurement","volume":"27","author":"Pandyan","year":"2005","journal-title":"Disabil. Rehabil."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1007\/s00415-018-8759-1","article-title":"Defining spasticity: A new approach considering current movement disorders terminology and botulinum toxin therapy","volume":"265","author":"Dressler","year":"2018","journal-title":"J. Neurol."},{"key":"ref_7","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_8","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.rehab.2018.04.004","article-title":"Onset, time course and prediction of spasticity after stroke or traumatic brain injury","volume":"62","author":"Sunnerhagen","year":"2019","journal-title":"Ann. Phys. Rehabil. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/BF03033927","article-title":"Neurophysiological effects of botulinum toxin type A","volume":"9","author":"Abbruzzese","year":"2006","journal-title":"Neurotox. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1002\/mds.22452","article-title":"Botulinum neurotoxins for post-stroke spasticity in adults: A systematic review","volume":"24","author":"Elia","year":"2009","journal-title":"Mov. Disord."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Asimakidou, E., and Sidiropoulos, C. (2023). A Bayesian Network Meta-Analysis and Systematic Review of Guidance Techniques in Botulinum Toxin Injections and Their Hierarchy in the Treatment of Limb Spasticity. Toxins, 15.","DOI":"10.3390\/toxins15040256"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1136\/jnnp.2009.177071","article-title":"Stop using the Ashworth Scale for the assessment of spasticity","volume":"81","author":"Fleuren","year":"2010","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"12431","DOI":"10.3390\/s130912431","article-title":"Surface electromyography signal processing and classification techniques","volume":"13","author":"Chowdhury","year":"2013","journal-title":"Sensors"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"44","DOI":"10.25259\/SRJHS_16_2025","article-title":"Hoffmann reflex parameters as neurophysiological biomarkers for quantifying spasticity: A systematic review","volume":"5","author":"Shah","year":"2025","journal-title":"Sri Ramachandra J. Health Sci."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Pulverenti, T.S., Zaaya, M., Grabowski, M., Grabowski, E., Islam, M.A., Li, J., Murray, L.M., and Knikou, M. (2021). Neurophysiological Changes After Paired Brain and Spinal Cord Stimulation Coupled with Locomotor Training in Human Spinal Cord Injury. Front. Neurol., 12.","DOI":"10.3389\/fneur.2021.627975"},{"key":"ref_16","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_17","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1007\/s00702-007-0869-3","article-title":"Evidence-based systematic review on the efficacy and safety of botulinum toxin-A therapy in post-stroke spasticity","volume":"115","author":"Rosales","year":"2008","journal-title":"J. Neural Transm."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1016\/j.apmr.2019.01.016","article-title":"Effectiveness of botulinum toxin treatment for upper limb spasticity poststroke over different ICF domains: A systematic review and meta-analysis","volume":"100","author":"Andringa","year":"2019","journal-title":"Arch. Phys. Med. Rehabil."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Weise, D., Weise, C.M., and Naumann, M. (2019). Central effects of botulinum neurotoxin\u2014Evidence from human studies. Toxins, 11.","DOI":"10.3390\/toxins11010021"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Hok, P., Veverka, T., Hlu\u0161t\u00edk, P., Nevrl\u00fd, M., and Ka\u0148ovsk\u00fd, P. (2021). The central effects of botulinum toxin in dystonia and spasticity. Toxins, 13.","DOI":"10.3390\/toxins13020155"},{"key":"ref_21","first-page":"103","article-title":"Use of surface EMG for evaluation of upper limb spasticity during botulinum toxin therapy in stroke patients","volume":"25","author":"Albani","year":"2010","journal-title":"Funct. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e01069","DOI":"10.1002\/brb3.1069","article-title":"Botulinum toxin A modifies nociceptive withdrawal reflex in subacute stroke patients","volume":"8","author":"Alvisi","year":"2018","journal-title":"Brain Behav."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e00173","DOI":"10.1002\/phy2.173","article-title":"Spinal plasticity in stroke patients after botulinum neurotoxin A injection in ankle plantar flexors","volume":"1","author":"Aymard","year":"2013","journal-title":"Physiol. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"36","DOI":"10.2340\/16501977-0120","article-title":"Associated reactions after stroke: A randomized controlled trial of the effect of botulinum toxin type A","volume":"40","author":"Bhakta","year":"2008","journal-title":"J. Rehabil. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1016\/j.jelekin.2013.07.002","article-title":"Changes in electromyographic activity after botulinum toxin injection of the rectus femoris in patients with hemiparesis walking with a stiff-knee gait","volume":"23","author":"Boudarham","year":"2013","journal-title":"J. Electromyogr. Kinesiol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Campanella, W., Corazza, A., Puce, L., Privitera, L., Pedrini, R., Mori, L., Boccuni, L., Turtulici, G., Trompetto, C., and Marinelli, L. (2022). Shear wave elastography combined with electromyography to assess the effect of botulinum toxin on spastic dystonia following stroke: A pilot study. Front. Neurol., 13.","DOI":"10.3389\/fneur.2022.980746"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"101434","DOI":"10.1016\/j.rehab.2020.09.002","article-title":"Effect of the combination of botulinum toxin A injection in elbow flexor muscles and rehabilitation on cortical oscillatory activity in individuals with stroke","volume":"64","author":"Chalard","year":"2021","journal-title":"Ann. Phys. Rehabil. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1186\/s12984-020-00716-z","article-title":"Precise quantification of the time course of voluntary activation capacity following botulinum toxin injections in the biceps brachii muscles of chronic stroke survivors","volume":"17","author":"Chandra","year":"2020","journal-title":"J. Neuroeng. Rehabil."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"036041","DOI":"10.1088\/1741-2552\/ac7666","article-title":"Anomalies of motor unit amplitude and territory after botulinum toxin injection","volume":"19","author":"Chandra","year":"2022","journal-title":"J. Neural Eng."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1016\/j.apmr.2005.03.019","article-title":"The use of a portable muscle tone measurement device to measure the effects of botulinum toxin type A on elbow flexor spasticity","volume":"86","author":"Chen","year":"2005","journal-title":"Arch. Phys. Med. Rehabil."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Chen, Y.-T., Liu, Y., Zhang, C., Magat, E., Zhou, P., Zhang, Y., and Li, S. (2022). Comprehensive assessment of the time course of biomechanical, electrophysiological and neuro-motor effects after botulinum toxin injections in elbow flexors of chronic stroke survivors with spastic hemiplegia: A cross sectional observation study. Toxins, 14.","DOI":"10.3390\/toxins14020104"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1177\/0269215509358945","article-title":"Does low-dose botulinum toxin help the recovery of arm function when given early after stroke? A phase II randomized controlled pilot study to estimate effect size","volume":"24","author":"Cousins","year":"2010","journal-title":"Clin. Rehabil."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.clinph.2021.12.019","article-title":"Botulinum toxin combined with rehabilitation decrease corticomuscular coherence in stroke patients","volume":"136","author":"Delcamp","year":"2022","journal-title":"Clin. Neurophysiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"412","DOI":"10.5114\/fn.2023.130030","article-title":"Botulinum neurotoxin-A in a patient with post-stroke spasticity: A neurophysiological study","volume":"61","author":"Fawzi","year":"2023","journal-title":"Folia Neuropathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"8","DOI":"10.23736\/S1973-9087.18.05168-7","article-title":"How effective is physical therapy for gait muscle activity in hemiparetic patients who receive botulinum toxin injections?","volume":"55","author":"Fujita","year":"2019","journal-title":"Eur. J. Phys. Rehabil. Med."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Gandolfi, M., Val\u00e8, N., Dimitrova, E.K., Mazzoleni, S., Battini, E., Filippetti, M., Picelli, A., Santamato, A., Gravina, M., and Saltuari, L. (2019). Effectiveness of robot-assisted upper limb training on spasticity, function and muscle activity in chronic stroke patients treated with botulinum toxin: A randomized single-blinded controlled trial. Front. Neurol., 10.","DOI":"10.3389\/fneur.2019.00041"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3039","DOI":"10.1097\/00001756-199709290-00008","article-title":"Botulinum toxin in upper limb spasticity: Study of reciprocal inhibition between forearm muscles","volume":"8","author":"Girlanda","year":"1997","journal-title":"NeuroReport"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1161\/01.STR.27.3.455","article-title":"Ankle muscle activity before and after botulinum toxin therapy for lower limb extensor spasticity in chronic hemiparetic patients","volume":"27","author":"Hesse","year":"1996","journal-title":"Stroke"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Hwang, I.-S., Ryu, J.-W., Jin, S., Kim, S.-A., and Kim, M.-S. (2024). Long-term enhancement of botulinum toxin injections for post-stroke spasticity by use of stretching exercises\u2014A randomized controlled trial. Toxins, 16.","DOI":"10.3390\/toxins16060267"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1177\/0269215513514983","article-title":"Does botulinum toxin injection site determine outcome in post-stroke plantarflexion spasticity? Comparison study of two injection sites in the gastrocnemius muscle: A randomized double-blind controlled trial","volume":"28","author":"Im","year":"2014","journal-title":"Clin. Rehabil."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"910","DOI":"10.2340\/16501977-2014","article-title":"Plastic changes in spinal synaptic transmission following botulinum toxin A in patients with post-stroke spasticity","volume":"47","author":"Kerzoncuf","year":"2015","journal-title":"J. Rehabil. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1097\/00002060-199811000-00012","article-title":"Comparison of phenol block and botulinum toxin type A in the treatment of spastic foot after stroke: A randomized, double-blind trial","volume":"77","author":"Kirazli","year":"1998","journal-title":"Am. J. Phys. Med. Rehabil."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1016\/j.apmr.2007.08.166","article-title":"Time course analysis of the effects of botulinum toxin type A on elbow spasticity based on biomechanic and electromyographic parameters","volume":"89","author":"Lee","year":"2008","journal-title":"Arch. Phys. Med. Rehabil."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1109\/TBME.2022.3208078","article-title":"Motor unit number estimation in spastic biceps brachii muscles of chronic stroke survivors before and after BoNT injection","volume":"70","author":"Liu","year":"2023","journal-title":"IEEE Trans. Biomed. Eng."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1113\/jphysiol.2012.239178","article-title":"Beyond muscular effects: Depression of spinal recurrent inhibition after botulinum neurotoxin A","volume":"591","author":"Aymard","year":"2013","journal-title":"J. Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"62","DOI":"10.2174\/2212707003666160728143344","article-title":"How botulinum toxin type A\u2013occupational therapy (OT)\u2013functional electrical stimulation (FES) modify spasticity and functional recovery in patients with upper limb spasticity post stroke","volume":"3","author":"Marvulli","year":"2016","journal-title":"Clin. Immunol. Endocr. Metab. Drugs"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s00415-004-0297-3","article-title":"Botulinum toxin in post-stroke patients: Stiffness modifications and clinical implications","volume":"251","author":"Miscio","year":"2004","journal-title":"J. Neurol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Nguyen, N., Houston, M., Liu, Y., Chen, Y.-T., Li, S., and Zhang, Y. (2024). High-density electromyography biomarkers for detecting and monitoring of spastic muscles during passive stretch. 2024 46th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), IEEE.","DOI":"10.1109\/EMBC53108.2024.10781738"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1191\/0269215502cr536oa","article-title":"Are we underestimating the clinical efficacy of botulinum toxin (type A)? Quantifying changes in spasticity, strength and upper limb function after injections of Botox\u00ae to the elbow flexors in a unilateral stroke population","volume":"16","author":"Pandyan","year":"2002","journal-title":"Clin. Rehabil."},{"key":"ref_50","first-page":"147","article-title":"Functional and clinical changes in upper limb spastic patients treated with botulinum toxin (BTX)","volume":"15","author":"Panizza","year":"2000","journal-title":"Funct. Neurol."},{"key":"ref_51","first-page":"265","article-title":"Change of stretch reflex threshold in spasticity: Effect of botulinum toxin injections","volume":"142","author":"Stampacchia","year":"2004","journal-title":"Arch. Ital. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.clineuro.2012.03.014","article-title":"Modification of altered ankle motor control after stroke using focal application of botulinum toxin type A","volume":"114","author":"Tang","year":"2012","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1111\/j.1468-1331.2008.02076.x","article-title":"Intrafusal effects of botulinum toxin in post-stroke upper limb spasticity","volume":"15","author":"Trompetto","year":"2008","journal-title":"Eur. J. Neurol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.jns.2015.12.049","article-title":"Sensorimotor modulation by botulinum toxin A in post-stroke arm spasticity: Passive hand movement","volume":"362","author":"Veverka","year":"2016","journal-title":"J. Neurol. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e26356","DOI":"10.1097\/MD.0000000000026356","article-title":"Cortical somatosensory processing after botulinum toxin therapy in post-stroke spasticity","volume":"100","author":"Veverka","year":"2021","journal-title":"Medicine"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"120588","DOI":"10.1016\/j.jns.2023.120588","article-title":"Interhemispheric parietal cortex connectivity reflects improvement in post-stroke spasticity due to treatment with botulinum toxin-A","volume":"446","author":"Veverka","year":"2023","journal-title":"J. Neurol. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Vinehout, K., Tynes, K., Sotelo, M.R., Hyngstrom, A.S., McGuire, J.R., and Schmit, B.D. (2021). Changes in cortical activity in stroke survivors undergoing botulinum neurotoxin therapy for treatment of focal spasticity. Front. Rehabil. Sci., 2.","DOI":"10.3389\/fresc.2021.735819"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Wang, R., G\u00e4verth, J., and Herman, P.A. (2018). Changes in the neural and non-neural related properties of the spastic wrist flexors after treatment with botulinum toxin A in post-stroke subjects: An optimization study. Front. Bioeng. Biotechnol., 6.","DOI":"10.3389\/fbioe.2018.00073"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1589\/jpts.27.759","article-title":"Gait improvement by low-dose botulinum toxin A injection treatment of the lower limbs in subacute stroke patients","volume":"27","author":"Wu","year":"2015","journal-title":"J. Phys. Ther. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1468-1331.2010.03125.x","article-title":"International consensus statement for the use of botulinum toxin treatment in adults and children with neurological impairments\u2014Introduction","volume":"17","author":"Esquenazi","year":"2010","journal-title":"Eur. J. Neurol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"jrm00134","DOI":"10.2340\/16501977-2753","article-title":"A practical guide to optimizing the benefits of post-stroke spasticity interventions with botulinum toxin A: An international group consensus","volume":"53","author":"Francisco","year":"2021","journal-title":"J. Rehabil. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"81","DOI":"10.2340\/16501977-0474","article-title":"Goal attainment scaling in the evaluation of treatment of upper limb spasticity with botulinum toxin: A secondary analysis from a double-blind placebo-controlled randomized clinical trial","volume":"42","author":"Baguley","year":"2010","journal-title":"J. Rehabil. Med."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Eeckhaut, B., Truijen, S., Leroij, C., D\u00e9vill\u00e9, J., Jacobs, L., and Saeys, W. (2026). Neurophysiological and structural-mechanical changes associated with dry needling in post-stroke spasticity: A systematic review. J. Clin. Med., 15.","DOI":"10.3390\/jcm15114246"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1310\/tsr1603-177","article-title":"Tonic stretch reflex threshold as a measure of spasticity: Implications for clinical practice","volume":"16","author":"Calota","year":"2009","journal-title":"Top. Stroke Rehabil."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"687","DOI":"10.2522\/ptj.20140243","article-title":"Tonic Stretch Reflex Threshold as a Measure of Ankle Plantar-Flexor Spasticity After Stroke","volume":"96","author":"Blanchette","year":"2016","journal-title":"Phys. Ther."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1016\/j.clinph.2021.02.390","article-title":"Tonic stretch reflex threshold as a measure of spasticity after stroke: Reliability, minimal detectable change and responsiveness","volume":"132","author":"Mullick","year":"2021","journal-title":"Clin. Neurophysiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.2522\/ptj.20130408","article-title":"Rehabilitation therapies after botulinum toxin-A injection to manage limb spasticity: A systematic review","volume":"94","author":"Kinnear","year":"2014","journal-title":"Phys. Ther."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.toxicon.2015.07.013","article-title":"Explanation of timing of botulinum neurotoxin effects, onset and duration, and clinical ways of influencing them","volume":"107","author":"Hallett","year":"2015","journal-title":"Toxicon"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Baricich, A., Wein, T., Cinone, N., Bertoni, M., Picelli, A., Chisari, C., Molteni, F., and Santamato, A. (2021). BoNT-A for post-stroke spasticity: Guidance on unmet clinical needs from a Delphi panel approach. Toxins, 13.","DOI":"10.3390\/toxins13040236"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1590\/S0004-282X2005000100035","article-title":"Botulinum toxin: Mechanisms of action","volume":"63","author":"Dressler","year":"2005","journal-title":"Arq. Neuro-Psiquiatr."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1002\/(SICI)1097-4598(199604)19:4<488::AID-MUS9>3.0.CO;2-8","article-title":"Extrafusal and intrafusal muscle effects in experimental botulinum toxin-A injection","volume":"19","author":"Rosales","year":"1996","journal-title":"Muscle Nerve"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Reebye, R., Jacinto, L.J., Balbert, A., Biering-Soerensen, B., Carda, S., Draulans, N., Molteni, F., O\u2019dEll, M.W., Picelli, A., and Santamato, A. (2024). Multimodal therapy and use of adjunctive therapies to BoNT-A in spasticity management: Defining terminology to help enhance spasticity treatment. Front. Neurol., 15.","DOI":"10.3389\/fneur.2024.1432330"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1186\/s13643-016-0384-4","article-title":"Rayyan\u2014A web and mobile app for systematic reviews","volume":"5","author":"Ouzzani","year":"2016","journal-title":"Syst. Rev."},{"key":"ref_75","unstructured":"Higgins, J.P.T., Thomas, J., Chandler, J., Cumpston, M., Li, T., Page, M., and Welch, V. (2024). Cochrane Handbook for Systematic Reviews of Interventions, Wiley."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"DerSimonian, R., and Laird, N. (1986). Meta-analysis in clinical trials. Controlled Clinical Trials, Elsevier.","DOI":"10.1016\/0197-2456(86)90046-2"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1136\/bmj.327.7414.557","article-title":"Measuring inconsistency in meta-analyses","volume":"327","author":"Higgins","year":"2003","journal-title":"BMJ"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"l4898","DOI":"10.1136\/bmj.l4898","article-title":"RoB 2: A revised tool for assessing risk of bias in randomised trials","volume":"366","author":"Sterne","year":"2019","journal-title":"BMJ"},{"key":"ref_79","unstructured":"Wells, G.A., Shea, B., O\u2019Connell, D., Peterson, J., Welch, V., Losos, M., and Tugwell, P. (2014). The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta-Analyses, Ottawa Hospital Research Institute."},{"key":"ref_80","unstructured":"Sch\u00fcnemann, H., Bro\u017cek, J., Guyatt, G., and Oxman, A. (2013). GRADE Handbook for Grading Quality of Evidence and Strength of Recommendations, GRADE Working Group."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/18\/9\/402\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:43:54Z","timestamp":1790012634000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/18\/9\/402"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,20]]},"references-count":80,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["toxins18090402"],"URL":"https:\/\/doi.org\/10.3390\/toxins18090402","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,20]]}}}