{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T22:39:06Z","timestamp":1772750346321,"version":"3.50.1"},"reference-count":41,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T00:00:00Z","timestamp":1718582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>Stiff-person syndrome is rare and disabling autoimmune condition that most frequently affects women, with no real predisposition by race. Diagnosis is often arduous, which is why patients concomitantly suffer from anxiety and depression. To date, drug therapy is based on the use of benzodiazepines, barbiturates, and baclofen. Refractory cases are treated with intravenous immunoglobulin, plasmapheresis, B lymphocyte depletion with rituximab, and even the implantation of intrathecal baclofen devices. Botulinum toxin injection is frequently used, even if it still has an unclear role in the literature. Our case report aims to demonstrate the efficacy of a combined treatment of botulinum toxin and therapeutic exercise in a 65-year-old patient with biceps brachii muscle hypertonia and diffuse spasms of the axial musculature, using rating scales such as the Numeric Rating Scale (NRS) and Modified Ashworth Scale (MAS), joint range of motion (ROM) measurement, and muscle dynamic stiffness mensuration, which is performed by using the MyotonPro\u00ae. All the assessments were conducted at the first evaluation (T0), soon after the combined treatment with botulin toxin and therapeutic exercise (T1), three months (T2), six months (T3), and eight months after the botulinum toxin injection (T4). The patient demonstrated benefits for more than 6 months with no side effects. The combined therapy of botulinum toxin and therapeutic exercise had an excellent result in our patient.<\/jats:p>","DOI":"10.3390\/diseases12060128","type":"journal-article","created":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T04:48:12Z","timestamp":1718599692000},"page":"128","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["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"],"prefix":"10.3390","volume":"12","author":[{"given":"Riccardo","family":"Marvulli","sequence":"first","affiliation":[{"name":"Department of Translational Biomedicine and Neuroscience (DiBraiN), Aldo Moro University, G. Cesare Place 11, 70125 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Vittoria","family":"Raele","sequence":"additional","affiliation":[{"name":"Department of Translational Biomedicine and Neuroscience (DiBraiN), Aldo Moro University, G. Cesare Place 11, 70125 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariagrazia","family":"Riccardi","sequence":"additional","affiliation":[{"name":"Department of Translational Biomedicine and Neuroscience (DiBraiN), Aldo Moro University, G. Cesare Place 11, 70125 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9953-5635","authenticated-orcid":false,"given":"Giacomo","family":"Far\u00ec","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Science and Technologies (Di.S.Te.B.A.), University of Salento, 73100 Lecce, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3169-3025","authenticated-orcid":false,"given":"Maurizio","family":"Ranieri","sequence":"additional","affiliation":[{"name":"Department of Translational Biomedicine and Neuroscience (DiBraiN), Aldo Moro University, G. Cesare Place 11, 70125 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8486-103X","authenticated-orcid":false,"given":"Marisa","family":"Megna","sequence":"additional","affiliation":[{"name":"Department of Translational Biomedicine and Neuroscience (DiBraiN), Aldo Moro University, G. Cesare Place 11, 70125 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,17]]},"reference":[{"key":"ref_1","first-page":"e11995","article-title":"Stiff-Person Syndrome: A Treatment Update and New Directions","volume":"12","author":"Ortiz","year":"2020","journal-title":"Cureus"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1055\/s-2008-1041222","article-title":"Stiff-man syndrome","volume":"11","author":"McEvoy","year":"1991","journal-title":"Semin. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1136\/practneurol-2011-000071","article-title":"Stiffpersonsyndrome","volume":"11","author":"Hadavi","year":"2011","journal-title":"Pract. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1097\/00007611-199508000-00002","article-title":"Stiff-man syndrome revisited","volume":"88","author":"Gerhardt","year":"1995","journal-title":"South. Med. J."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Vlad, B., Wang, Y., Newsome, S.D., and Balint, B. (2023). Stiff Person Spectrum Disorders-An Update and Outlook on Clinical, Pathophysiological and Treatment Perspectives. Biomedicines, 11.","DOI":"10.3390\/biomedicines11092500"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1002\/mds.10235","article-title":"Quality of life in stiff-person syndrome","volume":"17","author":"Gerschlager","year":"2002","journal-title":"Mov. Disord."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.psym.2020.08.005","article-title":"Stiff-Person Syndrome and Psychiatric Comorbidities: A Systematic Review","volume":"62","author":"Caffrey","year":"2021","journal-title":"J. Acad. Consult. Liaison Psychiatry"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"515","DOI":"10.2165\/00023210-200115070-00002","article-title":"Stiff man syndrome","volume":"15","author":"Meinck","year":"2001","journal-title":"CNS Drugs"},{"key":"ref_9","first-page":"749","article-title":"Stiff-PersonSyndrome","volume":"75","author":"Matsui","year":"2023","journal-title":"Brain Nerve"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1007\/s13311-022-01188-w","article-title":"Stiff-person Syndrome and GAD Antibody-spectrum Disorders: GABAergic Neuronal Excitability, Immunopathogenesis and Update on Antibody Therapies","volume":"19","author":"Dalakas","year":"2022","journal-title":"Neurotherapeutics"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.jns.2017.12.035","article-title":"Autoimmune and paraneoplastic movement disorders: An update","volume":"385","author":"Jankovic","year":"2018","journal-title":"J. Neurol. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1159\/000212375","article-title":"Stiff person syndrome","volume":"26","author":"Duddy","year":"2009","journal-title":"Front. Neurol. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1002\/mus.23234","article-title":"Autoimmune stiff person syndrome and related myelopathies: Understanding of electrophysiological and immunological processes","volume":"45","author":"Rakocevic","year":"2012","journal-title":"Muscle Nerve"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1007\/BF02938413","article-title":"Stiff-person syndrome","volume":"9","author":"Lockman","year":"2007","journal-title":"Curr. Treat. Options Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1136\/pgmj.74.877.641","article-title":"Stiff-man syndrome","volume":"74","author":"Rehman","year":"1998","journal-title":"Postgrad. Med. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1007\/s004150050425","article-title":"The stiff man and stiff man plus syndromes","volume":"246","author":"Brown","year":"1999","journal-title":"J. Neurol."},{"key":"ref_17","first-page":"90","article-title":"Side effects of treatment with benzodiazepines","volume":"22","author":"Uzun","year":"2010","journal-title":"Psychiatr. Danub."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"193","DOI":"10.2340\/16501977-2211","article-title":"Efficacy and safety of oral baclofen in the management of spasticity: A rationale for intrathecal baclofen","volume":"49","author":"Ertzgaard","year":"2017","journal-title":"J. Rehabil. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e200109","DOI":"10.1212\/NXI.0000000000200109","article-title":"Therapies in Stiff-Person Syndrome: Advances and Future Prospects Based on Disease Pathophysiology","volume":"10","author":"Dalakas","year":"2023","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_20","first-page":"222","article-title":"Anaesthetic management of Stiff Man syndrome","volume":"62","author":"Hernando","year":"2015","journal-title":"Rev. EspAnestesiol. Reanim."},{"key":"ref_21","first-page":"e6209","article-title":"Improving Ambulation and Minimizing Disability with Therapeutic Plasma Exchange in a Stiff-person Syndrome Patient with Recurrent Falls","volume":"11","author":"Sanchez","year":"2019","journal-title":"Cureus"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1177\/0961203320982668","article-title":"Rituximab\u2014The first twenty years","volume":"30","author":"Leandro","year":"2021","journal-title":"Lupus"},{"key":"ref_23","first-page":"e427","article-title":"Recent Advances and Review on Treatment of Stiff Person Syndrome in Adults and Pediatric Patients","volume":"7","author":"Bhatti","year":"2015","journal-title":"Cureus"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1111\/ner.12765","article-title":"Case Series: Intrathecal Baclofen Therapy in Stiff-Person Syndrome","volume":"21","author":"Abbatemarco","year":"2018","journal-title":"Neuromodulation"},{"key":"ref_25","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_26","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_27","doi-asserted-by":"crossref","unstructured":"Kaya Keles, C.S., and Ates, F. (2022). Botulinum Toxin Intervention in Cerebral Palsy-Induced Spasticity Management: Projected and Contradictory Effects on Skeletal Muscles. Toxins, 14.","DOI":"10.3390\/toxins14110772"},{"key":"ref_28","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_29","doi-asserted-by":"crossref","unstructured":"Ranieri, M., Marvulli, R., D\u2019Alesio, E., Riccardi, M., Raele, M.V., Dell\u2019Anna, L., Fai, A., Far\u00ec, G., and Megna, M. (2024). Effects of Intradermal Therapy (Mesotherapy) on BilateralCervicobrachial Pain. J. Pers. Med., 14.","DOI":"10.3390\/jpm14010122"},{"key":"ref_30","first-page":"453","article-title":"Spasticity in neurologicalpathologies. An update on the pathophysiological mechanisms, advances in diagnosis and treatment","volume":"70","author":"Albu","year":"2020","journal-title":"Rev. Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.cnp.2022.09.003","article-title":"Myoclonus and other jerky movement disorders","volume":"7","author":"Caviness","year":"2022","journal-title":"Clin. Neurophysiol. Pract."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1016\/S0140-6736(04)16207-7","article-title":"Cerebral palsy","volume":"363","author":"Koman","year":"2004","journal-title":"Lancet"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.3109\/02699052.2013.804202","article-title":"Spasticity after stroke: Physiology, assessment and treatment","volume":"27","author":"Thibaut","year":"2013","journal-title":"Brain Inj."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1136\/jnnp.69.2.143","article-title":"Botulinum toxin and spasticity","volume":"69","author":"Davis","year":"2000","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1212\/WNL.45.4.712","article-title":"Botulinum toxin A for spasticity, muscle spasms, and rigidity","volume":"45","author":"Grazko","year":"1995","journal-title":"Neurology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1097\/BPB.0000000000001055","article-title":"Adverse effects following botulinum toxin A injections in children with cerebral palsy","volume":"32","author":"Sapienza","year":"2023","journal-title":"J. Pediatr. Orthop. B"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1017\/cjn.2015.314","article-title":"Adverse Clinical Effects of Botulinum Toxin Intramuscular Injections for Spasticity","volume":"43","author":"Phadke","year":"2016","journal-title":"Can. J. Neurol. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/S1297-319X(02)00374-3","article-title":"Atypical low back pain: Stiff-person syndrome","volume":"69","author":"Gallien","year":"2002","journal-title":"Jt. Bone Spine"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1097\/01.NPT.0000282147.18446.b8","article-title":"Physical therapy during in-patient rehabilitation for a patient with Stiff-Person Syndrome","volume":"30","author":"Potter","year":"2006","journal-title":"J. Neurol. Phys. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.2522\/ptj.20100303","article-title":"Physical therapist management of stiff person syndrome in a 24-year-old woman","volume":"91","author":"Hegyi","year":"2011","journal-title":"Phys. Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s13760-020-01502-3","article-title":"The effect of clinical pilates-based physiotherapy program for a Stiff Person Syndrome patient: A case report","volume":"121","author":"Selcuk","year":"2021","journal-title":"Acta Neurol. Belg."}],"container-title":["Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-9721\/12\/6\/128\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:59:50Z","timestamp":1760108390000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-9721\/12\/6\/128"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,17]]},"references-count":41,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["diseases12060128"],"URL":"https:\/\/doi.org\/10.3390\/diseases12060128","relation":{},"ISSN":["2079-9721"],"issn-type":[{"value":"2079-9721","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,17]]}}}