{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:10:38Z","timestamp":1791288638416,"version":"4.3.0"},"reference-count":43,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T00:00:00Z","timestamp":1772668800000},"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>Stiff person syndrome (SPS) is an autoimmune disorder with muscle stiffness and spasms, for which current therapies provide incomplete relief. Botulinum neurotoxin (BoNT) has been explored as an adjunctive symptomatic treatment. The aim of this review was to critically evaluate the clinical evidence for BoNT therapy in SPS. Using Medline, Scopus and Google Scholar, we identified nine reports that were published up to 1 January 2026. English articles and articles with information on study type, type\/dose of BoNT and treatment results were included. One study was double-blind and placebo-controlled, one was retrospective and seven were single-case reports, comprising 46 patients. Open-label trials used botulinumtoxin-A (Botox, Dysport or Xeomin), while the blind study applied abobotulinumA (Dysport). All but one study (a case report) demonstrated motor improvement and a reduction in painful spasms associated with patient satisfaction. Reported doses ranged from 300 to 800 units for onabotulinumtoxinA and incobotulinumtoxinA and from 700 to 1000 units for abobotulinumtoxinA. The literature highlights the need for randomized clinical trials in larger cohorts, with careful selection of dose, injection sites, and adjunct physiotherapy, as well as an evaluation of early BoNT therapy in SPS. The novelty of this review lies in its critical synthesis of reported data and inclusion of most recent reports.<\/jats:p>","DOI":"10.3390\/toxins18030130","type":"journal-article","created":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T10:31:14Z","timestamp":1772706674000},"page":"130","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Botulinum Toxin Treatment of Stiff Person Syndrome\u2014A Critical Review and Update"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-5864-4300","authenticated-orcid":false,"given":"Ava Grace","family":"Tohidian","sequence":"first","affiliation":[{"name":"School of Medicine, Royal College of Surgeons, D02 YN77 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samira Marie","family":"Comtesse","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Goethe University, 60590 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahroo","family":"Etemadmoghadam","sequence":"additional","affiliation":[{"name":"Glenn Biggs Institute for Alzheimer\u2019s and Neurodegenerative Diseases, University of Texas Health San Antonio, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7204-8730","authenticated-orcid":false,"given":"Bahman","family":"Jabbari","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e200109","DOI":"10.1212\/NXI.0000000000200109","article-title":"Therapies in Stiff-Person Syndrome","volume":"10","author":"Dalakas","year":"2023","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1136\/jnnp-2014-309201","article-title":"Stiff-Person Syndrome: Insights into a Complex Autoimmune Disorder","volume":"86","author":"Jankovic","year":"2015","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"522","DOI":"10.7326\/0003-4819-131-7-199910050-00008","article-title":"The Stiff-Person Syndrome: An Autoimmune Disorder Affecting Neurotransmission of \u03b3-Aminobutyric Acid","volume":"131","author":"Levy","year":"1999","journal-title":"Ann. Intern. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"17562864211003486","DOI":"10.1177\/17562864211003486","article-title":"GAD Antibody-Spectrum Disorders: Progress in Clinical Phenotypes, Immunopathogenesis and Therapeutic Interventions","volume":"14","author":"Tsiortou","year":"2021","journal-title":"Ther. Adv. Neurol. Disord."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1136\/pn-2023-003974","article-title":"Stiff-Person Syndrome","volume":"25","author":"Bose","year":"2025","journal-title":"Pract. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.ncl.2012.09.005","article-title":"Stiff Person Syndrome","volume":"31","author":"Ciccotto","year":"2013","journal-title":"Neurol. Clin."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1097\/01.nrl.0000126587.37087.1a","article-title":"Stiff-Person Syndrome","volume":"10","author":"Murinson","year":"2004","journal-title":"Neurologist"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/B978-0-323-90820-7.00003-3","article-title":"Stiff person syndrome","volume":"203","author":"Cullinane","year":"2024","journal-title":"Handb. Clin. Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"577915","DOI":"10.1016\/j.jneuroim.2022.577915","article-title":"Stiff Person Syndrome Spectrum Disorders; More Than Meets the Eye","volume":"369","author":"Newsome","year":"2022","journal-title":"J. Neuroimmunol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Rakocevic, G., Alexopoulos, H., and Dalakas, M.C. (2019). Quantitative Clinical and Autoimmune Assessments in Stiff Person Syndrome: Evidence for a Progressive Disorder. BMC Neurol., 19.","DOI":"10.1186\/s12883-018-1232-z"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1002\/mds.870080323","article-title":"Significant improvement of stiff-person syndrome after paraspinal injection of botulinum toxin A","volume":"8","author":"Davis","year":"1993","journal-title":"Mov. Disord."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1002\/mds.870120636","article-title":"Botulinum toxin A improves muscle spasms and rigidity in stiff-person syndrome","volume":"12","author":"Liguori","year":"1997","journal-title":"Mov. Disord."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1002\/mus.23416","article-title":"Botulinum toxin A in anti-GAD-positive stiff-limb syndrome","volume":"46","author":"Anagnostou","year":"2012","journal-title":"Muscle Nerve"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.pmrj.2014.10.013","article-title":"Botulinum toxin a injection to facial and cervical paraspinal muscles in a patient with stiff person syndrome: A case report","volume":"7","author":"Pakeerappa","year":"2015","journal-title":"PM&R"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"S244","DOI":"10.1016\/j.pmrj.2016.07.431","article-title":"Poster 258 A Novel Approach to the Treatment of Stiff-Person-Syndrome with Botulinum Toxin: A Case Report","volume":"8","author":"Shah","year":"2016","journal-title":"PM&R"},{"key":"ref_16","first-page":"2580620","article-title":"Difficult to Treat Focal, Stiff Person Syndrome of the Left Upper Extremity","volume":"2017","author":"Esplin","year":"2017","journal-title":"Case Rep. Neurol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Marvulli, R., Raele, M.V., Riccardi, M., Far\u00ec, G., Ranieri, M., and Megna, M. (2024). The Effectiveness of Combining Botulinum Toxin Type A and Therapeutic Exercise in Treating Spasticity in a Patient with Complicated Stiff-Person Syndrome: A Case Report. Diseases, 12.","DOI":"10.3390\/diseases12060128"},{"key":"ref_18","first-page":"e94051","article-title":"Stiff-Person Syndrome: A Case Report and Treatment Modalities","volume":"17","author":"Nguyen","year":"2025","journal-title":"Cureus"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"17562864251377182","DOI":"10.1177\/17562864251377182","article-title":"Botulinum toxin as a potential adjunct therapy in stiff person syndrome spectrum disorders","volume":"18","author":"Roman","year":"2025","journal-title":"Ther. Adv. Neurol. Disord."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1002\/acn3.51791","article-title":"Stiff person spectrum disorder diagnosis, misdiagnosis, and suggested diagnostic criteria","volume":"10","author":"Chia","year":"2023","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1007\/s13311-021-01108-4","article-title":"Update on Intravenous Immunoglobulin in Neurology: Modulating Neuro-autoimmunity, Evolving Factors on Efficacy and Dosing and Challenges on Stopping Chronic IVIg Therapy","volume":"18","author":"Dalakas","year":"2021","journal-title":"Neurotherapeutics"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e200011","DOI":"10.1212\/NXI.0000000000200011","article-title":"Long-term Effectiveness of IVIg Maintenance Therapy in 36 Patients With GAD Antibody-Positive Stiff-Person Syndrome","volume":"9","author":"Yi","year":"2022","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s00415-025-13157-2","article-title":"Rituximab in stiff-person syndrome with glutamic acid decarboxylase 65 autoantibody: A systematic review","volume":"272","author":"Pignolo","year":"2025","journal-title":"J. Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1002\/ana.25002","article-title":"A double-blind, placebo-controlled study of rituximab in patients with stiff person syndrome","volume":"82","author":"Dalakas","year":"2017","journal-title":"Ann. Neurol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1113\/jphysiol.1949.sp004364","article-title":"The action of botulinum toxin on the neuro-muscular junction","volume":"109","author":"Burgen","year":"1949","journal-title":"J. Physiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1002\/mus.24776","article-title":"Randomized, placebo-controlled trial of incobotulinumtoxina for upper-limb post-stroke spasticity","volume":"53","author":"Elovic","year":"2016","journal-title":"Muscle Nerve"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"33","DOI":"10.3233\/NRE-210070","article-title":"Efficacy and safety of onabotulinumtoxinA with standardized physiotherapy for the treatment of pediatric lower limb spasticity: A randomized, placebo-controlled, phase III clinical trial","volume":"50","author":"Dimitrova","year":"2022","journal-title":"NeuroRehabilitation"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.1007\/s00415-020-09777-5","article-title":"Efficacy and safety of incobotulinumtoxinA in post-stroke upper-limb spasticity in Japanese subjects: Results from a randomized, double-blind, placebo-controlled study (J-PURE)","volume":"267","author":"Masakado","year":"2020","journal-title":"J. Neurol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.1212\/WNL.0000000000004687","article-title":"Efficacy and safety of abobotulinumtoxinA in spastic lower limb: Randomized trial and extension","volume":"89","author":"Gracies","year":"2017","journal-title":"Neurology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1002\/pmrj.12459","article-title":"The Effect of Repeated abobotulinumtoxinA (Dysport\u00ae) Injections on Walking Velocity in Persons with Spastic Hemiparesis Caused by Stroke or Traumatic Brain Injury","volume":"13","author":"Esquenazi","year":"2021","journal-title":"PM&R"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1002\/ana.25340","article-title":"Efficacy of Botulinum Toxin A for Treating Cramps in Diabetic Neuropathy","volume":"84","author":"Restivo","year":"2018","journal-title":"Ann. Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"17562864251376821","DOI":"10.1177\/17562864251376821","article-title":"Botulinum toxin in stiff person syndrome: How useful is it in helping muscle stiffness and spasms?","volume":"18","author":"Dalakas","year":"2025","journal-title":"Ther. Adv. Neurol. Disord."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1212\/WNL.55.10.1531","article-title":"The clinical spectrum of anti-GAD antibody-positive patients with stiff-person syndrome","volume":"55","author":"Dalakas","year":"2000","journal-title":"Neurology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1212\/WNL.0000000000003789","article-title":"Safety and efficacy of incobotulinumtoxinA doses up to 800 U in limb spasticity: The TOWER study","volume":"88","author":"Wissel","year":"2017","journal-title":"Neurology"},{"key":"ref_35","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_36","doi-asserted-by":"crossref","unstructured":"Jankovic, J., Carruthers, J., Naumann, M., Ogilvie, P., Boodhoo, T., Attar, M., Gupta, S., Singh, R., Soliman, J., and Yushmanova, I. (2023). Neutralizing Antibody Formation with OnabotulinumtoxinA (BOTOX\u00ae) Treatment from Global Registration Studies across Multiple Indications: A Meta-Analysis. Toxins, 15.","DOI":"10.3390\/toxins15050342"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e2109","DOI":"10.1212\/WNL.0000000000009444","article-title":"Frequency and risk factors of antibody-induced secondary failure of botulinum neurotoxin therapy","volume":"94","author":"Walter","year":"2020","journal-title":"Neurology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.neuroscience.2017.06.004","article-title":"Antinociceptive effect of botulinum toxin A involves alterations in AMPA receptor expression and glutamate release in spinal dorsal horn neurons","volume":"357","author":"Hong","year":"2017","journal-title":"Neuroscience"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Marinelli, S., Pavone, F., and Luvisetto, S. (2025). Pharmacological Interaction of Botulinum Neurotoxins with Excitatory and Inhibitory Neurotransmitter Systems Involved in the Modulation of Inflammatory Pain. Toxins, 17.","DOI":"10.3390\/toxins17080374"},{"key":"ref_40","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_41","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1097\/PHM.0b013e31813e2b4d","article-title":"Botulinum toxin a, evidence-based exercise therapy, and constraint-induced movement therapy for upper-limb hemiparesis attributable to stroke: A preliminary study","volume":"86","author":"Levy","year":"2007","journal-title":"Am. J. Phys. Med. Rehabil."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"7385","DOI":"10.4081\/ni.2018.7385","article-title":"Efficacy of physical therapy associated with botulinum toxin type A on functional performance in post-stroke spasticity: A randomized, double-blinded, placebo-controlled trial","volume":"10","author":"Prazeres","year":"2018","journal-title":"Neurol. Int."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Facciorusso, S., Spina, S., Filippetti, M., Reebye, R., Francisco, G.E., and Santamato, A. (2025). Botulinum Toxin Combined with Robot-Assisted Therapy for Post-Stroke Spasticity: A Systematic Review. Toxins, 17.","DOI":"10.3390\/toxins17120569"}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/18\/3\/130\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T10:46:52Z","timestamp":1772707612000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/18\/3\/130"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,5]]},"references-count":43,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["toxins18030130"],"URL":"https:\/\/doi.org\/10.3390\/toxins18030130","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,5]]}}}