{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T14:48:58Z","timestamp":1764600538408,"version":"3.46.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Blepharospasm (BSP) is a functionally disabling disease with a marked impact on the quality of life of patients. Botulinum toxin (BoNT) injections have been recommended as first-line therapy for BSP. However, the clinical benefits of BoNT are temporary with only about 8\u201310\u202fweeks duration of benefit in most patients with BSP. Per previous case reports, regular use of topical frankincense essential oil (FEO) can achieve significant symptom relief and can decrease the frequency of BoNT injections. This trial will explore whether BoNT combined with regular application of FEO can improve clinical outcomes in patients with BSP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>This protocol describes an open-label, randomized controlled trial to be undertaken to evaluate daily topical application of FEO and coconut oil (CO) in patients with BSP. The goal is to enroll 32 patients with BSP who have received immediate BoNT injection in each treatment arm. Only patients who have previously received less than 12\u202fweeks of positive benefits from BoNT therapy will be enrolled. The primary outcome will be the duration of symptom improvement after the intervention with BoNT combined with FEO or CO within the 24-week follow-up period. Symptom improvement is defined as a decrease of one point or more in the Jankovic Rating Scale severity score compared to baseline in patients with BSP. Secondary outcomes will consist of changes in BSP symptom severity, disability, and quality of life from baseline to each time point after the intervention. Safety analysis will be based on the presence of localized skin allergic reactions and adverse events. Outcomes will be assessed at baseline and at weeks 2, 4, 8, 12, 16, 20, and 24 after the therapy begins.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This study will provide evidence that FEO therapy is a promising non-invasive therapy that can be easily combined with BoNT injections to improve clinical outcomes in patients with BSP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.chictr.org.cn\/<\/jats:ext-link>\n                      , identifier ChiCTR2400091987.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2025.1693914","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T14:45:26Z","timestamp":1764600326000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and safety of combination of frankincense and botulinum toxin in the treatment of blepharospasm: a protocol for a single-centre, open-label, randomized, controlled trial"],"prefix":"10.3389","volume":"16","author":[{"given":"Shiyuan","family":"Gong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuhan","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiana","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feiwen","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhengkun","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zilin","family":"Ou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhicong","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weixi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,1]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1002\/mdc3.13524","article-title":"The prevalence of idiopathic or inherited isolated dystonia: a systematic review and meta-analysis","volume":"9","author":"Medina","year":"2022","journal-title":"Mov Disord Clin Pract"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1212\/WNL.0b013e31829bfdf6","article-title":"Development and validation of a clinical guideline for diagnosing blepharospasm","volume":"81","author":"Defazio","year":"2013","journal-title":"Neurology"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1002\/mds.26934","article-title":"Blepharospasm 40 years later","volume":"32","author":"Defazio","year":"2017","journal-title":"Mov Disord"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1668","DOI":"10.1093\/brain\/awr224","article-title":"The non-motor syndrome of primary dystonia: clinical and pathophysiological implications","volume":"135","author":"Stamelou","year":"2012","journal-title":"Brain"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"2780","DOI":"10.1007\/s00415-019-09484-w","article-title":"Motor and non-motor symptoms in blepharospasm: clinical and pathophysiological implications","volume":"266","author":"Ferrazzano","year":"2019","journal-title":"J Neurol"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/j.parkreldis.2013.10.008","article-title":"Impaired cognitive functions in adult-onset primary cranial cervical dystonia","volume":"20","author":"Romano","year":"2014","journal-title":"Parkinsonism Relat Disord"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1097\/icu.0000000000000500","article-title":"Developments in the treatment of benign essential blepharospasm","volume":"29","author":"Yen","year":"2018","journal-title":"Curr Opin Ophthalmol"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1016\/j.brs.2018.02.004","article-title":"Combined effects of rTMS and botulinum toxin therapy in benign essential blepharospasm","volume":"11","author":"Shukla","year":"2018","journal-title":"Brain Stimul"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"2036","DOI":"10.1016\/s0161-6420(95)30757-9","article-title":"Long-term changes in duration of relief with botulinum toxin treatment of essential blepharospasm and hemifacial spasm","volume":"102","author":"Ainsworth","year":"1995","journal-title":"Ophthalmology"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1007\/s13760-014-0285-z","article-title":"Long-term therapy of benign essential blepharospasm and facial hemispasm with botulinum toxin A: retrospective assessment of the clinical and quality of life impact in patients treated for more than 15 years","volume":"114","author":"Streitov\u00e1","year":"2014","journal-title":"Acta Neurol Belg"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"Cd004900","DOI":"10.1002\/14651858.CD004900.pub3","article-title":"Botulinum toxin type a therapy for blepharospasm","volume":"11","author":"Duarte","year":"2020","journal-title":"Cochrane Database Syst Rev"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"17562864221138144","DOI":"10.1177\/17562864221138144","article-title":"Effects of non-invasive brain stimulation in dystonia: a systematic review and meta-analysis","volume":"15","author":"Morrison-Ham","year":"2022","journal-title":"Ther Adv Neurol Disord"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"2031","DOI":"10.1212\/WNL.0b013e3181c5b42d","article-title":"Blepharospasm and the modulation of cortical excitability in primary and secondary motor areas","volume":"73","author":"Kranz","year":"2009","journal-title":"Neurology"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1465","DOI":"10.1212\/WNL.0b013e3181f8814d","article-title":"Transcranial magnetic brain stimulation modulates blepharospasm: a randomized controlled study","volume":"75","author":"Kranz","year":"2010","journal-title":"Neurology"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1007\/s10072-016-2703-x","article-title":"Transcranial direct current stimulation for patients with benign essential blepharospasm: a case report","volume":"38","author":"Trebossen","year":"2017","journal-title":"Neurol Sci"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"101848","DOI":"10.1016\/j.ajoc.2023.101848","article-title":"Possible role of frankincense in the treatment of benign essential blepharospasm","volume":"30","author":"Baker","year":"2023","journal-title":"Am J Ophthalmol Case Rep"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"349","DOI":"10.2165\/11586800-000000000-00000","article-title":"Boswellia serrata: an overall assessment of in vitro, preclinical, pharmacokinetic and clinical data","volume":"50","author":"Abdel-Tawab","year":"2011","journal-title":"Clin Pharmacokinet"},{"key":"ref18","first-page":"281","article-title":"Effects of Boswellia serrata resin extract on motor dysfunction and brain oxidative stress in an experimental model of Parkinson's disease","volume":"9","author":"Doaee","year":"2019","journal-title":"Avicenna J Phytomed"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"112250","DOI":"10.1016\/j.biopha.2021.112250","article-title":"Mechanistic role of boswellic acids in Alzheimer's disease: emphasis on anti-inflammatory properties","volume":"144","author":"Siddiqui","year":"2021","journal-title":"Biomed Pharmacother"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1136\/jnnp-2017-317101","article-title":"A standardised frankincense extract reduces disease activity in relapsing-remitting multiple sclerosis (the SABA phase IIa trial)","volume":"89","author":"St\u00fcrner","year":"2018","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1052","DOI":"10.3390\/antiox14091052","article-title":"Dystonia versus redox balance: a preliminary assessment of oxidative stress in patients","volume":"14","author":"Koptielow","year":"2025","journal-title":"Antioxidants"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"e7586","DOI":"10.1136\/bmj.e7586","article-title":"SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials","volume":"346","author":"Chan","year":"2013","journal-title":"BMJ"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1016\/s1474-4422(14)70143-7","article-title":"Pallidal neurostimulation in patients with medication-refractory cervical dystonia: a randomised, sham-controlled trial","volume":"13","author":"Volkmann","year":"2014","journal-title":"Lancet Neurol"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.1002\/mds.23658","article-title":"Efficacy and safety of incobotulinumtoxinA (NT 201, Xeomin) in the treatment of blepharospasm-a randomized trial","volume":"26","author":"Jankovic","year":"2011","journal-title":"Mov Disord"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1002\/mds.22368","article-title":"Relationship between various clinical outcome assessments in patients with blepharospasm","volume":"24","author":"Jankovic","year":"2009","journal-title":"Mov Disord"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1002\/mds.26156","article-title":"Development and validation of a clinical scale for rating the severity of blepharospasm","volume":"30","author":"Defazio","year":"2015","journal-title":"Mov Disord"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1212\/wnl.35.1.73","article-title":"Validity and reliability of a rating scale for the primary torsion dystonias","volume":"35","author":"Burke","year":"1985","journal-title":"Neurology"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1136\/bmj.305.6846.160","article-title":"Validating the SF-36 health survey questionnaire: new outcome measure for primary care","volume":"305","author":"Brazier","year":"1992","journal-title":"BMJ"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1136\/jnnp.2003.013441","article-title":"Craniocervical dystonia questionnaire (CDQ-24): development and validation of a disease-specific quality of life instrument","volume":"75","author":"M\u00fcller","year":"2004","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/s0885-3924(00)00146-9","article-title":"Management of spasticity associated pain with botulinum toxin A","volume":"20","author":"Wissel","year":"2000","journal-title":"J Pain Symptom Manag"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/0022-3956(75)90026-6","article-title":"\"mini-mental state\". A practical method for grading the cognitive state of patients for the clinician","volume":"12","author":"Folstein","year":"1975","journal-title":"J Psychiatr Res"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1111\/j.2044-8341.1959.tb00467.x","article-title":"The assessment of anxiety states by rating","volume":"32","author":"Hamilton","year":"1959","journal-title":"Br J Med Psychol"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1136\/jnnp.23.1.56","article-title":"A rating scale for depression","volume":"23","author":"Hamilton","year":"1960","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1001\/archpsyc.1989.01810110048007","article-title":"The Yale-Brown obsessive compulsive scale. I. Development, use, and reliability","volume":"46","author":"Goodman","year":"1989","journal-title":"Arch Gen Psychiatry"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/0165-1781(89)90047-4","article-title":"The Pittsburgh sleep quality index: a new instrument for psychiatric practice and research","volume":"28","author":"Buysse","year":"1989","journal-title":"Psychiatry Res"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1078\/094471103321648593","article-title":"Efficacy and tolerability of Boswellia serrata extract in treatment of osteoarthritis of knee-a randomized double blind placebo controlled trial","volume":"10","author":"Kimmatkar","year":"2003","journal-title":"Phytomedicine"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"R85","DOI":"10.1186\/ar2461","article-title":"A double blind, randomized, placebo controlled study of the efficacy and safety of 5-Loxin for treatment of osteoarthritis of the knee","volume":"10","author":"Sengupta","year":"2008","journal-title":"Arthritis Res Ther"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.semcancer.2020.01.015","article-title":"Anti-inflammatory and anti-cancer activities of frankincense: targets, treatments and toxicities","volume":"80","author":"Efferth","year":"2022","journal-title":"Semin Cancer Biol"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"114942","DOI":"10.1016\/j.foodres.2024.114942","article-title":"Comparison and identification of aroma components in 21 kinds of frankincense with variety and region based on the odor intensity characteristic spectrum constructed by HS-SPME-GC-MS combined with E-nose","volume":"195","author":"Chen","year":"2024","journal-title":"Food Res Int"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1002\/mds.870090216","article-title":"Development of resistance to botulinum toxin type a in patients with torticollis","volume":"9","author":"Greene","year":"1994","journal-title":"Mov Disord"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"491","DOI":"10.3390\/toxins11090491","article-title":"Immunogenicity associated with botulinum toxin treatment","volume":"11","author":"Bellows","year":"2019","journal-title":"Toxins"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.ajo.2024.10.007","article-title":"Combination of pretarsal and preseptal botulinum toxin injections in the treatment of blepharospasm: a prospective nonrandomized clinical trial","volume":"270","author":"Hu","year":"2024","journal-title":"Am J Ophthalmol"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2025.1693914\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T14:45:27Z","timestamp":1764600327000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2025.1693914\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,1]]},"references-count":42,"alternative-id":["10.3389\/fneur.2025.1693914"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2025.1693914","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,1]]},"article-number":"1693914"}}