{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T03:23:56Z","timestamp":1790047436884,"version":"4.0.1"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005639","name":"Universidade De S\u00e3o Paulo","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005639","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neurol Sci"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Tolosa-Hunt Syndrome (THS) is a rare, painful ophthalmoplegia caused by granulomatous inflammation within the cavernous sinus. Despite the effective response to corticosteroid therapy, recurrence rates reported in the literature vary significantly, and clear associated factors of recurrence remain elusive. This systematic review and meta-analysis aim to establish the frequency of relapse and identify f actors associated with recurrence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Evidence acquisition<\/jats:title>\n                    <jats:p>Following PRISMA guidelines, we performed a comprehensive database search of MEDLINE\/PubMed, EMBASE, and Scopus from inception to June 2024, focusing on observational studies or case series reporting THS recurrence. Meta-analysis employed a random-effects model to estimate pooled recurrence rates. Meta-regression analyses evaluated clinical and demographic associated factors of recurrence, with publication bias assessed via funnel plots and Egger\u2019s test.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Seventeen studies encompassing 456 patients met the inclusion criteria. The pooled recurrence rate was 23% (95% CI, 17\u201332%), with substantial heterogeneity (I\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200959.9%). The frequency of cranial nerve involvement specifically nerves II, IV, and VI, correlated with higher recurrence risk (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05). Age, sex, duration of follow-up, and MRI abnormalities did not show significant associations. Limited data were available concerning the use of steroid-sparing immunosuppressants, inflammatory biomarkers, and characteristics of MRI.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Approximately one-quarter of patients with THS experience recurrence. Involvement of cranial nerves II, IV, and VI was associated with relapses. Further prospective investigations with standardized recurrence definitions and structured therapeutic comparisons are needed to clarify prognostic factors and optimize long-term management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10072-026-08985-7","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T08:55:51Z","timestamp":1774515351000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Relapse in Tolosa-Hunt syndrome: pooled recurrence rates and associated factors from a meta-analysis of 456 cases"],"prefix":"10.1007","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9008-5202","authenticated-orcid":false,"given":"Bernardo Leite Pond\u00e9","family":"da Luz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilherme Diogo","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,26]]},"reference":[{"issue":"4","key":"8985_CR1","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1136\/jnnp.17.4.300","volume":"17","author":"E Tolosa","year":"1954","unstructured":"Tolosa E (1954) Periateritic lesions of the carotid siphon with the clinical features of a carotid infraclinodal aneurysm. J Neurol Neurosurg Psychiatry 17(4):300\u2013302. https:\/\/doi.org\/10.1136\/jnnp.17.4.300","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"1","key":"8985_CR2","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1212\/WNL.11.1.56","volume":"11","author":"WE Hunt","year":"1961","unstructured":"Hunt WE, Meagher JN, LeFever HE, Zeman W (1961) Painful ophthalmoplegia: its relation to indolent inflammation of the cavernous sinus. Neurology 11(1):56\u201356. https:\/\/doi.org\/10.1212\/WNL.11.1.56","journal-title":"Neurology"},{"key":"8985_CR3","doi-asserted-by":"crossref","unstructured":"Smith JL, Taxdal DS (1966) Painful ophthalmoplegia. The Tolosa-Hunt syndrome. Am J Ophthalmol 61(6):1466\u20131472. https:\/\/pubmed.ncbi.nlm.nih.gov\/5938314\/. Accessed 17 July 2024","DOI":"10.1016\/0002-9394(66)90487-9"},{"key":"8985_CR4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2024.110858","volume":"129","author":"HS Ahmed","year":"2024","unstructured":"Ahmed HS, Shivananda DB, Pulkurthi SR, Dias AF, Sahoo PP (2024) Clinical profile and outcomes in Tolosa-Hunt syndrome; a systematic review. J Clin Neurosci 129:110858. https:\/\/doi.org\/10.1016\/j.jocn.2024.110858","journal-title":"J Clin Neurosci"},{"issue":"3","key":"8985_CR5","doi-asserted-by":"publisher","first-page":"287","DOI":"10.2298\/vsp150703180p","volume":"74","author":"A Podgorac","year":"2017","unstructured":"Podgorac A, Zidverc-Trajkovic J, Jovanovic Z et al (2017) Tolosa-Hunt syndrome: is it necessary to show granuloma? - The report of eight cases. Vojnosanit Pregl 74(3):287\u2013293. https:\/\/doi.org\/10.2298\/vsp150703180p","journal-title":"Vojnosanit Pregl"},{"issue":"3","key":"8985_CR6","doi-asserted-by":"publisher","first-page":"251","DOI":"10.5152\/npa.2016.13791","volume":"54","author":"\u00c7K Akpinar","year":"2017","unstructured":"Akpinar \u00c7K, \u00d6zbenli T, Do\u011fru H, Incesu L (2017) Tolosa-Hunt syndrome - cranial neuroimaging findings. Noro Psikiyatr Ars 54(3):251\u2013254. https:\/\/doi.org\/10.5152\/npa.2016.13791","journal-title":"Noro Psikiyatr Ars"},{"issue":"4","key":"8985_CR7","doi-asserted-by":"publisher","first-page":"302","DOI":"10.4103\/aian.AIAN_368_18","volume":"21","author":"S Arthur","year":"2018","unstructured":"Arthur S et al (2018) Clinical profile and long-term outcome of Tolosa-Hunt syndrome. Ann Indian Acad Neurol 21(4):302\u2013306. https:\/\/doi.org\/10.4103\/aian.AIAN_368_18","journal-title":"Ann Indian Acad Neurol"},{"key":"8985_CR8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ensci.2021.100359","volume":"24","author":"F Ata","year":"2021","unstructured":"Ata F, Yousaf Z, Arachchige SNM, Rose S, Alshurafa A, Muthanna B, Bilal AIB, El Beltagi AE, Zahid M (2021) The demographics of Tolosa-Hunt syndrome in Qatar. eNeurologicalSci 24:100359\u2013100359. https:\/\/doi.org\/10.1016\/j.ensci.2021.100359","journal-title":"eNeurologicalSci"},{"issue":"1","key":"8985_CR9","doi-asserted-by":"publisher","DOI":"10.1186\/s12886-021-02007-0","volume":"21","author":"H Kim","year":"2021","unstructured":"Kim H, Oh SY (2021) The clinical features and outcomes of Tolosa-Hunt syndrome. BMC Ophthalmol 21(1):237. https:\/\/doi.org\/10.1186\/s12886-021-02007-0","journal-title":"BMC Ophthalmol"},{"issue":"10","key":"8985_CR10","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1177\/0333102412475238","volume":"33","author":"CH Hung","year":"2013","unstructured":"Hung CH, Chang KH, Wu YM, Chen YL, Lyu RK, Chang HS, Wu YR, Chen CM, Huang CC, Chu CC, Liao MF, Wai YY, Hsu SP, Ro LS (2013) A comparison of benign and inflammatory manifestations of Tolosa-Hunt syndrome. Cephalalgia 33(10):842\u2013852. https:\/\/doi.org\/10.1177\/0333102412475238","journal-title":"Cephalalgia"},{"key":"8985_CR11","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71","author":"MJ Page","year":"2021","unstructured":"Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE, Chou R, Glanville J, Grimshaw JM, Hr\u00f3bjartsson A, Lalu MM, Li T, Loder EW, Mayo-Wilson E, McDonald S, McGuinness LA, Stewart LA, Thomas J, Tricco AC, Welch VA, Whiting P, Moher D (2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. https:\/\/doi.org\/10.1136\/bmj.n71","journal-title":"BMJ"},{"issue":"1","key":"8985_CR12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1177\/0333102417738202","volume":"38","author":"International Headache Society","year":"2018","unstructured":"International Headache Society (2018) Headache classification committee of the international headache society (IHS) the international classification of headache disorders, 3rd edition. Cephalalgia 38(1):1\u2013211. https:\/\/doi.org\/10.1177\/0333102417738202","journal-title":"Cephalalgia"},{"issue":"5","key":"8985_CR13","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1080\/01658107.2024.2336270","volume":"48","author":"E Ertilav","year":"2024","unstructured":"Ertilav E, Akyol A (2024) Evaluation of patients with painful ophthalmoplegia for benign and secondary etiologies. Neuro-Ophthalmology 48(5):338\u2013347. https:\/\/doi.org\/10.1080\/01658107.2024.2336270","journal-title":"Neuro-Ophthalmology"},{"key":"8985_CR14","doi-asserted-by":"publisher","DOI":"10.1186\/s41983-023-00667-x","author":"VN Rodge","year":"2023","unstructured":"Rodge VN, Mukherjee A, Biswas S, Majumdar S, Gangopadhyay G (2023) Clinical and radiological profile of cavernous sinus syndrome: a study from eastern part of India. Egypt J Neurol Psychiatry Neurosurg. https:\/\/doi.org\/10.1186\/s41983-023-00667-x","journal-title":"Egypt J Neurol Psychiatry Neurosurg"},{"key":"8985_CR15","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.pediatrneurol.2016.06.017","volume":"62","author":"CA P\u00e9rez","year":"2016","unstructured":"P\u00e9rez CA, Evangelista M (2016) Evaluation and management of Tolosa\u2013Hunt syndrome in children: a clinical update. Pediatr Neurol 62:18\u201326. https:\/\/doi.org\/10.1016\/j.pediatrneurol.2016.06.017","journal-title":"Pediatr Neurol"},{"key":"8985_CR16","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.clineuro.2017.02.017","volume":"155","author":"S Bhatkar","year":"2017","unstructured":"Bhatkar S, Goyal MK, Takkar A, Mukherjee KK, Singh P, Singh R, Lal V (2017) Cavernous sinus syndrome: a prospective study of 73 cases at a tertiary care centre in Northern India. Clin Neurol Neurosurg 155:63\u201369. https:\/\/doi.org\/10.1016\/j.clineuro.2017.02.017","journal-title":"Clin Neurol Neurosurg"},{"issue":"1\u20132","key":"8985_CR17","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.jns.2014.03.031","volume":"341","author":"X Zhang","year":"2014","unstructured":"Zhang X, Zhang W, Liu R, Dong Z, Yu S (2014) Factors that influence Tolosa\u2013Hunt syndrome and the short-term response to steroid pulse treatment. J Neurol Sci 341(1\u20132):13\u201316. https:\/\/doi.org\/10.1016\/j.jns.2014.03.031","journal-title":"J Neurol Sci"},{"issue":"6","key":"8985_CR18","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1007\/s10072-015-2124-2","volume":"36","author":"R Hao","year":"2015","unstructured":"Hao R, He Y, Zhang H, Zhang W, Li X, Ke Y (2015) The evaluation of ICHD-3 beta diagnostic criteria for Tolosa\u2013Hunt syndrome: a study of 22 cases of Tolosa\u2013Hunt syndrome. Neurol Sci 36(6):899\u2013905. https:\/\/doi.org\/10.1007\/s10072-015-2124-2","journal-title":"Neurol Sci"},{"issue":"11","key":"8985_CR19","doi-asserted-by":"publisher","first-page":"1717","DOI":"10.3341\/jkos.2009.50.11.1717","volume":"50","author":"HK Lee","year":"2009","unstructured":"Lee HK, Lee SG (2009) Clinical observations on tolosa-hunt syndrome. J Korean Ophthalmol Soc 50(11):1717. https:\/\/doi.org\/10.3341\/jkos.2009.50.11.1717","journal-title":"J Korean Ophthalmol Soc"},{"issue":"5","key":"8985_CR20","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1111\/j.1440-1673.2008.01988.x","volume":"52","author":"R Jain","year":"2008","unstructured":"Jain R, Sawhney S, Koul RL, Chand P (2008) Tolosa-hunt syndrome: MRI appearances. J Med Imaging Radiat Oncol 52(5):447\u2013451. https:\/\/doi.org\/10.1111\/j.1440-1673.2008.01988.x","journal-title":"J Med Imaging Radiat Oncol"},{"issue":"4","key":"8985_CR21","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1097\/wnq.0b013e31818d0980","volume":"18","author":"R T\u00fcrko\u011flu","year":"2008","unstructured":"T\u00fcrko\u011flu R, Balak N, Tireli H (2008) Surgery with cavernous sinus syndrome. Neurosurg Q 18(4):230\u2013238. https:\/\/doi.org\/10.1097\/wnq.0b013e31818d0980","journal-title":"Neurosurg Q"},{"issue":"5","key":"8985_CR22","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1097\/MD.0b013e318156c67f","volume":"86","author":"S Fern\u00e1ndez","year":"2007","unstructured":"Fern\u00e1ndez S, Godino O, Mart\u00ednez-Y\u00e9lamos S et al (2007) Cavernous sinus syndrome: a series of 126 patients. Medicine (Baltimore) 86(5):278\u2013281. https:\/\/doi.org\/10.1097\/MD.0b013e318156c67f","journal-title":"Medicine (Baltimore)"},{"issue":"1","key":"8985_CR23","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1590\/s0004-282x1997000100016","volume":"55","author":"E Carrilho","year":"1997","unstructured":"Carrilho E, Yamamoto FI, Scaff M (1997) S\u00edndrome de Tolosa-Hunt: dificuldades no diagn\u00f3stico e padr\u00e3o de resposta \u00e0 prednisona. Arq Neuropsiquiatr 55(1):101\u2013105. https:\/\/doi.org\/10.1590\/s0004-282x1997000100016","journal-title":"Arq Neuropsiquiatr"},{"issue":"3","key":"8985_CR24","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1007\/bf00313284","volume":"224","author":"D Inzitari","year":"1981","unstructured":"Inzitari D, Sit D, Marconi GP, Barontini F (1981) The tolosa-hunt syndrome: further clinical and pathogenetic considerations based on the study of eight cases. J Neurol 224(3):221\u2013228. https:\/\/doi.org\/10.1007\/bf00313284","journal-title":"J Neurol"},{"key":"8985_CR25","unstructured":"Gim\u00e9nez-Rold\u00e1n S, Guillem A, Mu\u00f1oz L (2006) Long-term risk of relapses in Tolosa-Hunt syndrome. Neurologia (Barcelona, Spain) 21(7):382\u2013385. https:\/\/pubmed.ncbi.nlm.nih.gov\/16977560\/. Accessed 17 July 2024"},{"issue":"2","key":"8985_CR26","doi-asserted-by":"publisher","first-page":"198","DOI":"10.4103\/aian.aian_368_18","volume":"23","author":"S Arthur","year":"2020","unstructured":"Arthur S et al (2020) Tolosa-hunt syndrome: long-term outcome and role of steroid-sparing agents. Ann Indian Acad Neurol 23(2):198\u2013203. https:\/\/doi.org\/10.4103\/aian.aian_368_18","journal-title":"Ann Indian Acad Neurol"}],"container-title":["Neurological Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10072-026-08985-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10072-026-08985-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10072-026-08985-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T20:54:01Z","timestamp":1781643241000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10072-026-08985-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,26]]},"references-count":26,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["8985"],"URL":"https:\/\/doi.org\/10.1007\/s10072-026-08985-7","relation":{},"ISSN":["1590-1874","1590-3478"],"issn-type":[{"value":"1590-1874","type":"print"},{"value":"1590-3478","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,26]]},"assertion":[{"value":"23 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"No conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This study is a systematic review and meta-analysis based exclusively on previously published aggregated data. No human participants were directly recruited or enrolled, no new patient data were collected, and no identifiable patient information was handled. Under Brazilian regulations , this type of study is exempt from Research Ethics Committee approval and informed consent.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}],"article-number":"378"}}