{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T09:18:25Z","timestamp":1793092705311,"version":"4.5.0"},"reference-count":52,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"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>Spasmodic dysphonia (SD) is a rare neurological disorder that impairs phonatory function by triggering involuntary and intermittent contractions of the intrinsic laryngeal muscles. SD is classified into three types: adductor SD (AdSD), abductor SD (AbSD), and mixed SD. Of these, AdSD accounts for 90\u201395% of disease; younger females are predominantly affected. Botulinum toxin injection into the laryngeal muscles is safe, minimally invasive, and very effective. Here, we review the history of clinical research for SD conducted in Japan. The first use of botulinum toxin injection therapy to treat SD in Japan was by Kobayashi et al. in 1989. The group developed an objective mora (syllable) method to evaluate SD severity. Recently, we conducted a placebo-controlled, randomized, double-blinded clinical trial of botulinum toxin therapy for AdSD and an open-label trial for AbSD to obtain the approval of such therapy by the Japanese medical insurance system. The mora method revealed significant voice improvement and the evidence was of high quality. Additionally, a clinical trial of type 2 thyroplasty using titanium bridges confirmed the efficacy and safety of such therapy. These studies broadened the SD treatment options and have significantly benefited patients.<\/jats:p>","DOI":"10.3390\/toxins14070451","type":"journal-article","created":{"date-parts":[[2022,7,4]],"date-time":"2022-07-04T23:38:55Z","timestamp":1656977935000},"page":"451","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Botulinum Toxin Therapy for Spasmodic Dysphonia in Japan: The History and an Update"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9144-3242","authenticated-orcid":false,"given":"Masamitsu","family":"Hyodo","sequence":"first","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Kochi Medical School Hospital, Kohasu, Okou-cho, Nankoku 783-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kahori","family":"Hirose","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Kochi Medical School Hospital, Kohasu, Okou-cho, Nankoku 783-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asuka","family":"Nagao","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Kochi Medical School Hospital, Kohasu, Okou-cho, Nankoku 783-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya","family":"Nakahira","sequence":"additional","affiliation":[{"name":"Rehabilitation Department, Kochi Medical School Hospital, Kohasu, Okou-cho, Nankoku 783-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taisuke","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Kochi Medical School Hospital, Kohasu, Okou-cho, Nankoku 783-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,1]]},"reference":[{"key":"ref_1","unstructured":"Aronson, A.E., and Bless, D.M. (2009). Spasmodic Dysphonia, Clinical Voice Disorders, Thieme Medical Publishers. [4th ed.]."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1523\/JNEUROSCI.2758-10.2011","article-title":"Spasmodic dysphonia: A laryngeal control disorder specific to speech","volume":"31","author":"Ludlow","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1002\/lary.27003","article-title":"Phenomenology, genetics and CNS network abnormalities in laryngeal dystonia: A 30-year experience","volume":"128","author":"Blitzer","year":"2018","journal-title":"Laryngoscope"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"14705","DOI":"10.1523\/JNEUROSCI.0407-13.2013","article-title":"Abnormal striatal dopaminergic neurotransmission during rest and task production in spasmodic dysphonia","volume":"33","author":"Simonyan","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Kodama, N., Sanuki, T., Miyamoto, T., and Tashiro, J. (J. Voice, 2021). Effects and differences of voice therapy on spasmodic dysphonia and muscle tension dysphonia: A retrospective pilot study, J. Voice, in press.","DOI":"10.1016\/j.jvoice.2021.07.003"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1288\/00005537-198301000-00002","article-title":"Intermediate results of 306 recurrent laryngeal nerve sections for spastic dysphonia","volume":"93","author":"Dedo","year":"1983","journal-title":"Laryngoscope"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1177\/000348949610500802","article-title":"Long-term follow-up of recurrent laryngeal nerve avulsion for the treatment of spastic dysphonia","volume":"105","author":"Weed","year":"1996","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1177\/000348940611500203","article-title":"Treatment of adductor-type spasmodic dysphonia by surgical myectomy: A preliminary report","volume":"115","author":"Koufman","year":"2006","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1080\/00016480801965019","article-title":"Surgical treatment for adductor spasmodic dysphonia\u2014Efficacy of bilateral thyroarytenoid myectomy under microlaryngoscopy","volume":"128","author":"Nakamura","year":"2008","journal-title":"Acta Otolaryngol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1177\/000348949910800302","article-title":"Selective laryngeal adductor denervation-reinnervation: A new surgical treatment for adductor spasmodic dysphonia","volume":"108","author":"Berke","year":"1999","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1097\/00005537-200104000-00011","article-title":"Thyroplasty for adductor spasmodic dysphonia: Further experiences","volume":"111","author":"Isshiki","year":"2001","journal-title":"Laryngoscope"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1177\/0194599817705612","article-title":"Long-term evaluation of type 2 thyroplasty with titanium bridges for adductor spasmodic dysphonia","volume":"157","author":"Sanuki","year":"2017","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1067\/mjd.2000.105567","article-title":"Pharmacology of botulinum toxin","volume":"43","author":"Huang","year":"2000","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/j.1468-1331.2010.03047.x","article-title":"Spasmodic dysphonia and botulinum toxin: Experience from the largest treatment series","volume":"17","author":"Blitzer","year":"2010","journal-title":"Eur. J. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1007\/s00702-007-0757-x","article-title":"Evidence for the effectiveness of botulinum toxin for spasmodic dysphonia from high-quality research designs","volume":"115","author":"Watts","year":"2008","journal-title":"J. Neural. Transm."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1097\/01.moo.0000145959.50513.5e","article-title":"Contemporary management of spasmodic dysphonia","volume":"12","author":"Sulica","year":"2004","journal-title":"Curr. Opin. Otolaryngol. Head Neck Surg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1002\/mds.870030302","article-title":"Epidemiology of focal and generalized dystonia in Rochester, Minnesota","volume":"3","author":"Nutt","year":"1988","journal-title":"Mov. Disord."},{"key":"ref_18","first-page":"121","article-title":"The epidemiology of the primary dystonias in the north of England","volume":"78","author":"Duffey","year":"1998","journal-title":"Adv. Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Epidemiological Study of Dystonia in Europe (ESDE) Collaborative Group (2000). A prevalence study of primary dystonia in eight European countries. J. Neurol., 247, 787\u2013792.","DOI":"10.1007\/s004150070094"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1159\/000059525","article-title":"Service-based survey of dystonia in Munich","volume":"21","author":"Kamm","year":"2002","journal-title":"Neuroepidemiology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1002\/mds.20674","article-title":"Prevalence study of primary dystonia in Iceland","volume":"21","author":"Asgeirsson","year":"2006","journal-title":"Mov. Disord."},{"key":"ref_22","unstructured":"(2022, May 20). National Spasmodic Dysphonia Association: Spasmodic Dysphonia. Available online: https:\/\/dysphonia.org\/about-sd\/what-is-spasmodic-dysphonia\/onset-diagnosis-sd\/."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"343","DOI":"10.5112\/jjlp.42.343","article-title":"Epidemiological investigation on spasmodic dysphonia\u2014Investigation by questionnaire","volume":"2","author":"Yamazaki","year":"2001","journal-title":"Jpn. J. Logop. Phoniatr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.anl.2020.08.013","article-title":"The prevalence and clinical features of spasmodic dysphonia: A review of epidemiological surveys conducted in Japan","volume":"48","author":"Hyodo","year":"2021","journal-title":"Auris Nasus Larynx"},{"key":"ref_25","first-page":"129","article-title":"Investigative study on adductor spasmodic dysphonia","volume":"54","author":"Inoue","year":"2013","journal-title":"Pholia Phoniat. Jpn."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.otohns.2008.05.624","article-title":"Research priorities in spasmodic dysphonia","volume":"139","author":"Ludlow","year":"2008","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Hyodo, M., Asano, K., Nagao, A., Hirose, K., Nakahira, M., Yanagida, S., and Nishizawa, N. (2021). Botulinum toxin therapy: A series of clinical studies on patients with spasmodic dysphonia in Japan. Toxins, 13.","DOI":"10.3390\/toxins13120840"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1288\/00005537-198806000-00012","article-title":"Clinical and laboratory characteristics of laryngeal dystonia: A study of 110 cases","volume":"98","author":"Blitzer","year":"1988","journal-title":"Laryngoscope"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/S0967-5868(03)00020-1","article-title":"Spasmodic dysphonia: Clinical features and effects of botulinum toxin therapy in 169 patients\u2014An Australian experience","volume":"10","author":"Tisch","year":"2003","journal-title":"J. Clin. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1002\/lary.21395","article-title":"Botulinum toxin treatment of adductor spasmodic dysphonia: Longitudinal functional outcomes","volume":"121","author":"Novakovic","year":"2011","journal-title":"Laryngoscope"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1177\/0003489415588557","article-title":"The Mayo Clinic Arizona spasmodic dysphonia experience: A demographic analysis of 718 patients","volume":"124","author":"Patel","year":"2015","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_32","first-page":"S1","article-title":"Clinical Practice Guideline: Hoarseness (Dysphonia) (Update)","volume":"158","author":"Stachler","year":"2018","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_33","first-page":"CD004327","article-title":"Botulinum toxin injections for the treatment of spasmodic dysphonia","volume":"3","author":"Watts","year":"2004","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_34","first-page":"237","article-title":"Laryngeal dystonia (spasmodic dysphonia): Observations of 901 patients and treatment with botulinum toxin","volume":"78","author":"Brin","year":"1998","journal-title":"Adv. Neurol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1016\/j.otohns.2005.09.008","article-title":"Botulinum toxin A and B: A comparative dosing study for spasmodic dysphonia","volume":"133","author":"Blitzer","year":"2005","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.jvoice.2016.09.022","article-title":"Botulinum Toxin-A dosing trends for adductor spasmodic dysphonia at a single institution over 10 years","volume":"31","author":"Bradley","year":"2017","journal-title":"J. Voice"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1044\/1092-4388(2002\/037)","article-title":"Taylor M: Botox treatment in adductor spasmodic dysphonia: A meta-analysis","volume":"45","author":"Boutsen","year":"2002","journal-title":"J. Speech Lang. Hear. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/1746-160X-5-20","article-title":"Unilateral versus bilateral thyroarytenoid Botulinum toxin injections in adductor spasmodic dysphonia: A prospective study","volume":"5","author":"Upile","year":"2009","journal-title":"Head Face Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/S0892-1997(05)80038-4","article-title":"A comparison of injection techniques using botulinum toxin injection for treatment of the spasmodic dysphonias","volume":"6","author":"Ludlow","year":"1992","journal-title":"J. Voice"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1001\/archotol.131.9.793","article-title":"Safety of simultaneous bilateral botulinum toxin injections for abductor spasmodic dysphonia","volume":"131","author":"Stong","year":"2005","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"155","DOI":"10.3109\/00016489309128145","article-title":"Botulinum toxin treatment for spasmodic dysphonia","volume":"504","author":"Kobayashi","year":"1993","journal-title":"Acta Otolaryngol. Suppl."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"67","DOI":"10.5426\/larynx1989.16.2_67","article-title":"Botulinum toxin injection for spasmodic dysphonia in Japan\u20141486 injections for 260 cases in 15 years","volume":"16","author":"Kumada","year":"2004","journal-title":"Larynx Jpn."},{"key":"ref_43","first-page":"237","article-title":"The effects of botulinum toxin injection treatment administered to patients with adductor spasmodic dysphonia\u2014Longitudinal subjective vocal changes","volume":"58","author":"Omori","year":"2017","journal-title":"Pholia. Phoniat. Jpn."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1159\/000052650","article-title":"The syllable method: Proportion of impaired syllables as an indicator of spasmodic dysphonia severity","volume":"53","author":"Kumada","year":"2001","journal-title":"Folia. Phoniatr. Logoped."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"332","DOI":"10.5112\/jjlp.42.332","article-title":"Voice assessments in patients with spasmodic dysphonia","volume":"42","author":"Makiyama","year":"2001","journal-title":"Jpn. J. Logop. Phoniatr."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1111\/ene.14714","article-title":"Botulinum toxin injection into the intrinsic laryngeal muscles to treat spasmodic dysphonia: A multicenter, placebo-controlled, randomized, double-blinded, parallel-group comparison\/open-label clinical trial","volume":"28","author":"Hyodo","year":"2021","journal-title":"Eur. J. Neurol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1002\/lio2.669","article-title":"Post-treatment clinical course following botulinum toxin injection therapy for adductor spasmodic dysphonia: Analysis of data from a placebo-controlled, randomized, double-blinded clinical trial in Japan","volume":"6","author":"Hirose","year":"2021","journal-title":"Laryngoscope Investig. Otolaryngol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1002\/lary.26265","article-title":"Gender differences in onabotulinum toxin A dosing for adductor spasmodic dysphonia","volume":"127","author":"Lerner","year":"2017","journal-title":"Laryngoscope"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"74","DOI":"10.5426\/larynx1989.16.2_74","article-title":"Bilateral thyroarytenoid myectomy for adductor spasmodic dysphonia","volume":"16","author":"Watanabe","year":"2004","journal-title":"Larynx Jpn."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.otohns.2009.12.018","article-title":"Effects of type II thyroplasty on adductor spasmodic dysphonia. Effects of type II thyroplasty on adductor spasmodic dysphonia","volume":"142","author":"Sanuki","year":"2010","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Sanuki, T. (2022). Spasmodic dysphonia: An overview of clinical features and treatment options. Auris Nasus Larynx.","DOI":"10.1016\/j.anl.2022.05.012"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.anl.2019.09.004","article-title":"A summary of the Clinical Practice Guideline for the Diagnosis and Management of Voice Disorders, 2018 in Japan","volume":"47","author":"Umeno","year":"2020","journal-title":"Auris Nasus Larynx"}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/14\/7\/451\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:41:38Z","timestamp":1760139698000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/14\/7\/451"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,1]]},"references-count":52,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["toxins14070451"],"URL":"https:\/\/doi.org\/10.3390\/toxins14070451","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,1]]}}}