Extensive Multilevel Spinal and Extraspinal Involvement in a Case of Calvarial Tuberculosis: A Rare Disseminated Presentation

Extensive Multilevel Spinal and Extraspinal Involvement in a Case of Calvarial Tuberculosis: A Rare Disseminated Presentation | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Systematic Review Extensive Multilevel Spinal and Extraspinal Involvement in a Case of Calvarial Tuberculosis: A Rare Disseminated Presentation harsh patel, preeti singh, abhaya kumar This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6604450/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Calvarial tuberculosis (TB) is an uncommon manifestation of skeletal TB, and its progression to disseminated involvement of multiple systems is exceedingly rare. We report a unique case of a patient initially diagnosed with calvarial TB, who subsequently developed widespread involvement of the cervical and lumbar spine, bilateral paraspinal soft tissues, the right psoas muscle, and pulmonary parenchyma. Imaging studies demonstrated intraosseous abscesses, soft tissue masses, and compressive epidural components, consistent with disseminated TB. The patient was advised to undergo fluid aspiration for microbiological confirmation and drug susceptibility testing, in view of possible drug-resistant TB. This case underscores the need for high clinical suspicion, early diagnosis, and systemic evaluation in patients with skeletal TB to identify and manage potentially disseminated disease. Calvarial tuberculosis disseminated TB spinal TB psoas abscess drug-resistant tuberculosis vertebral osteolysis Figures Figure 1 Figure 2 Introduction Tuberculosis remains a significant global health issue, with extrapulmonary manifestations accounting for nearly 15–20% of cases. Skeletal TB, although uncommon, can present with a wide spectrum of manifestations depending on the anatomical site. Calvarial TB is rare, representing less than 1% of skeletal TB, and dissemination to the spine or soft tissue is even more infrequent (1,2) . We report a unique case of disseminated TB presenting initially with calvarial involvement and subsequently demonstrating extensive vertebral, paravertebral, and pulmonary disease. Case Presentation A 6-year-old child presented with a history of fall from height, impacting the occipital region. Initial CT brain showed no significant abnormality. Two weeks later, the patient developed an occipital swelling. Imaging suggested a midline occipital bone defect with soft tissue lesion, initially suspected as an intradiploic epidermoid cyst. The patient underwent suboccipital craniotomy, and histopathology confirmed calvarial tuberculosis. Follow-up imaging one month later showed near-complete resolution of scalp and extradural soft tissue involvement. However, a whole-spine MRI revealed disseminated abnormalities in the cervical and lumbar spine with intraosseous abscesses, vertebral osteolysis, and paraspinal masses (3,4) . Additional findings included a large right psoas abscess and pulmonary involvement with cervical and mediastinal lymphadenopathy. In view of extensive involvement, aspiration was advised to assess for drug-resistant TB. Discussion This case illustrates a rare and aggressive form of disseminated TB that initially presented as localized calvarial tuberculosis. Calvarial TB is a rare entity, accounting for 0.2–1.3% of skeletal TB (4,5) . It commonly presents with scalp swelling and punched-out bone defects on imaging (1,2,6) . MRI plays a crucial role in evaluating extent and complications (8) . Dissemination to multiple spinal levels and extraspinal sites such as the psoas muscle and lungs is exceedingly rare (7,9). Spinal TB usually affects contiguous vertebral segments, and extensive multi-regional involvement—as seen in this case—is atypical (8,9) . The presence of a large psoas abscess, epidural extension, and lung involvement raises suspicion of drug-resistant TB or hematogenous spread from a primary pulmonary focus (7) . The need for early microbiological confirmation, culture, and drug susceptibility testing is emphasized to guide targeted therapy (9) . This case also highlights the importance of considering tuberculosis in differential diagnosis of unusual scalp swellings and skull lesions, especially in endemic regions (6,7). Conclusion This case underscores the importance of systemic evaluation in skeletal TB, particularly when initial lesions are found in atypical locations such as the calvarium. Disseminated TB with spinal, extraspinal, and pulmonary involvement should prompt early microbiological workup, especially to rule out drug-resistant strains, and initiate aggressive, tailored treatment. Declarations a. Funding The authors did not receive support from any organization for the submitted work. b. Conflicts of interest/Competing interests (include appropriate disclosures) The authors have no conflicts of interest to declare that are relevant to the content of this article c. Ethics approval and consent to participate The study is approved by institutional ethics committee (IEC). Written consent has been taken from the participant parent to publish the study. d. Availability of data and material : not applicable e. Consent for publication All authors have reviewed and approved the final version of the manuscript f. Authors' contributions Dr Harsh : conceived and designed the study Dr Preeti : contributed to the data analysis and wrote the manuscript Dr Abhaya Kumar : provided critical feedback and revised the manuscript g. Acknowledgement : We acknowledge our department of neurosurgery References Ramdurg SR, Gupta DK, Suri A, et al. Calvarial tuberculosis: uncommon manifestation of common disease—a series of 21 cases. Br J Neurosurg. 2010;24(5):572–577. doi:10.3109/02688697.2010.495166 Diyora B, Kumar R, Modgi R, et al. Calvarial tuberculosis: a report of eleven patients. Neurol India. 2009;57(5):607. doi:10.4103/0028-3886.57814 Barton CJ. Tuberculosis of the vault of the skull. Br J Radiol. 1961;34(401):286–290. doi:10.1259/0007-1285-34-401-286 Mukherjee KK, Kaushik R, Nada R, et al. Calvarial tuberculosis. Surg Neurol. 2002;57(3):195–202. doi:10.1016/S0090-3019(02)00632-8 Calvarial tuberculosis in patient with cervical tuberculous lymphadenitis: a case report. Cureus. 2024. Available at: https://www.cureus.com/articles/194932 Skull base and calvarial tuberculosis: a rare presentation. Clin Radiol. 2020. Available at: https://www.sciencedirect.com/science/article/pii/S0019570720300111 Calvarial tuberculosis: an unusual presentation. BMJ Case Rep. 2019;12(4):e226967. doi:10.1136/bcr-2018-226967 MRI findings in spinal tuberculosis. Orthobullets. Available at: https://www.orthobullets.com/spine/2027/spinal-tuberculosis Atypical spinal tuberculosis: a case report. Exp Ther Med. 2020;20(6):163. doi:10.3892/etm.2019.8014 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6604450","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Systematic Review","associatedPublications":[],"authors":[{"id":460603741,"identity":"2a0ae7b6-ba30-4565-8af4-fbe1b1b79da9","order_by":0,"name":"harsh patel","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAx0lEQVRIiWNgGAWjYBACAwbmgw8SDCTkQJwDD4jTwpZs8KDCxhisJYE4LTxmgg/OpCU2gHhEaTGXbktjSGw7nD4/7PBDoC12croNBLRYzjl87AFQS+7G22kGQC3JxmYHCDnsRlq6AVjL7ASQlgOJ2whryTGTADnMcHb6BxK0JJxJS5CXziHWljvHkg0SKmwMN0jnFBxIMCDGL7ebDz78YSAhLz87ffOHDxV2cgS1MEjA9IJVGhBSjqxFvoEY1aNgFIyCUTAiAQDAzU27VpaInwAAAABJRU5ErkJggg==","orcid":"","institution":"Kokilaben Dhirubhai Ambani Hospital","correspondingAuthor":true,"prefix":"","firstName":"harsh","middleName":"","lastName":"patel","suffix":""},{"id":460603742,"identity":"353079b8-3e25-4cc1-83f3-a42aaf1d1fc8","order_by":1,"name":"preeti singh","email":"","orcid":"","institution":"Kokilaben Dhirubhai Ambani Hospital","correspondingAuthor":false,"prefix":"","firstName":"preeti","middleName":"","lastName":"singh","suffix":""},{"id":460603743,"identity":"a21e1668-f631-4c76-ab01-ad9de2fd3abc","order_by":2,"name":"abhaya kumar","email":"","orcid":"","institution":"Kokilaben Dhirubhai Ambani Hospital","correspondingAuthor":false,"prefix":"","firstName":"abhaya","middleName":"","lastName":"kumar","suffix":""}],"badges":[],"createdAt":"2025-05-06 15:08:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6604450/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6604450/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":83751543,"identity":"db7e9c6c-8e77-4be0-9888-e6c4a42b496b","added_by":"auto","created_at":"2025-06-02 07:06:42","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":376080,"visible":true,"origin":"","legend":"\u003cp\u003ea) CT Brain b) MRI Brain suggestive of a\u003cstrong\u003emidline occipital bone defect is occupied by a soft tissue lesion.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"qlmdOWJRloGTQm8w0UmfQf0Zu4iuezBJg.png","url":"https://assets-eu.researchsquare.com/files/rs-6604450/v1/633aedff2e34b3966ad5c868.png"},{"id":83752267,"identity":"344cada1-4f91-4e39-a3d3-a0445ef8d941","added_by":"auto","created_at":"2025-06-02 07:14:43","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":3797379,"visible":true,"origin":"","legend":"\u003cp\u003eFigure 3 a) Abnormal signal intensity was noted in the C5–C7 vertebral bodies, with heterogeneous post-contrast enhancement. The C6 vertebral body showed osteolysis, and a non-enhancing intraosseous abscess was identified. An anterior epidural soft tissue component was compressing the anterior subarachnoid space. A large perivertebral soft tissue mass extended from C2–C3 levels.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eFigure 3 b) L2–L4 vertebral bodies showed abnormal marrow signal with heterogeneous enhancement and areas of non-enhancement, suggesting necrosis or abscess formation. An anterior epidural soft tissue mass at L2 compressed the thecal sac, and a paravertebral soft tissue component was observed at L4.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eFigure 3c) MRI Brain complete resolution of the soft tissue component overlying the scalp and extradural space\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6604450/v1/7822e2d3221d87c6432d17bf.png"},{"id":85347122,"identity":"a7420fa6-be9f-4f70-a90a-75288300a877","added_by":"auto","created_at":"2025-06-25 02:16:53","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5460380,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6604450/v1/f3a4c50c-73ae-4499-818e-c3cdbc65cbee.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Extensive Multilevel Spinal and Extraspinal Involvement in a Case of Calvarial Tuberculosis: A Rare Disseminated Presentation","fulltext":[{"header":"Introduction","content":"\u003cp\u003eTuberculosis remains a significant global health issue, with extrapulmonary manifestations accounting for nearly 15\u0026ndash;20% of cases. Skeletal TB, although uncommon, can present with a wide spectrum of manifestations depending on the anatomical site. Calvarial TB is rare, representing less than 1% of skeletal TB, and dissemination to the spine or soft tissue is even more infrequent \u003csup\u003e(1,2)\u003c/sup\u003e. We report a unique case of disseminated TB presenting initially with calvarial involvement and subsequently demonstrating extensive vertebral, paravertebral, and pulmonary disease.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 6-year-old child presented with a history of fall from height, impacting the occipital region. Initial CT brain showed no significant abnormality. Two weeks later, the patient developed an occipital swelling. Imaging suggested a midline occipital bone defect with soft tissue lesion, initially suspected as an intradiploic epidermoid cyst.\u003c/p\u003e\n\u003cp\u003eThe patient underwent suboccipital craniotomy, and histopathology confirmed calvarial tuberculosis. Follow-up imaging one month later showed near-complete resolution of scalp and extradural soft tissue involvement. However, a whole-spine MRI revealed disseminated abnormalities in the cervical and lumbar spine with intraosseous abscesses, vertebral osteolysis, and paraspinal masses \u003csup\u003e(3,4)\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eAdditional findings included a large right psoas abscess and pulmonary involvement with cervical and mediastinal lymphadenopathy. In view of extensive involvement, aspiration was advised to assess for drug-resistant TB.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis case illustrates a rare and aggressive form of disseminated TB that initially presented as localized calvarial tuberculosis. Calvarial TB is a rare entity, accounting for 0.2\u0026ndash;1.3% of skeletal TB \u003csup\u003e(4,5)\u003c/sup\u003e. It commonly presents with scalp swelling and punched-out bone defects on imaging \u003csup\u003e(1,2,6)\u003c/sup\u003e. MRI plays a crucial role in evaluating extent and complications \u003csup\u003e(8)\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDissemination to multiple spinal levels and extraspinal sites such as the psoas muscle and lungs is exceedingly rare (7,9). Spinal TB usually affects contiguous vertebral segments, and extensive multi-regional involvement\u0026mdash;as seen in this case\u0026mdash;is atypical \u003csup\u003e(8,9)\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe presence of a large psoas abscess, epidural extension, and lung involvement raises suspicion of drug-resistant TB or hematogenous spread from a primary pulmonary focus \u003csup\u003e(7)\u003c/sup\u003e. The need for early microbiological confirmation, culture, and drug susceptibility testing is emphasized to guide targeted therapy \u003csup\u003e(9)\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis case also highlights the importance of considering tuberculosis in differential diagnosis of unusual scalp swellings and skull lesions, especially in endemic regions\u003csup\u003e\u0026nbsp;(6,7).\u003c/sup\u003e\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis case underscores the importance of systemic evaluation in skeletal TB, particularly when initial lesions are found in atypical locations such as the calvarium. Disseminated TB with spinal, extraspinal, and pulmonary involvement should prompt early microbiological workup, especially to rule out drug-resistant strains, and initiate aggressive, tailored treatment.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cspan\u003ea. \u003cstrong\u003eFunding \u003c/strong\u003eThe authors did not receive support from any organization for the submitted work.\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eb. \u003cstrong\u003eConflicts of interest/Competing interests\u003c/strong\u003e (include appropriate disclosures) The authors have no conflicts of interest to declare that are relevant to the content of this article\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003ec. \u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e The study is approved by institutional ethics committee (IEC). Written consent has been taken from the participant parent to publish the study.\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003ed. \u003cstrong\u003eAvailability of data and material :\u003c/strong\u003e not applicable\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003ee. \u003cstrong\u003eConsent for publication\u003c/strong\u003e All authors have reviewed and approved the final version of the manuscript\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003ef. \u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e Dr Harsh : conceived and designed the study Dr Preeti : contributed to the data analysis and wrote the manuscript Dr Abhaya Kumar : provided critical feedback and revised the manuscript\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eg. \u003cstrong\u003eAcknowledgement \u003c/strong\u003e: We acknowledge our department of neurosurgery\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eRamdurg SR, Gupta DK, Suri A, et al. Calvarial tuberculosis: uncommon manifestation of common disease\u0026mdash;a series of 21 cases. Br J Neurosurg. 2010;24(5):572\u0026ndash;577. doi:10.3109/02688697.2010.495166\u003c/li\u003e\n \u003cli\u003eDiyora B, Kumar R, Modgi R, et al. Calvarial tuberculosis: a report of eleven patients. Neurol India. 2009;57(5):607. doi:10.4103/0028-3886.57814\u003c/li\u003e\n \u003cli\u003eBarton CJ. Tuberculosis of the vault of the skull. Br J Radiol. 1961;34(401):286\u0026ndash;290. doi:10.1259/0007-1285-34-401-286\u003c/li\u003e\n \u003cli\u003eMukherjee KK, Kaushik R, Nada R, et al. Calvarial tuberculosis. Surg Neurol. 2002;57(3):195\u0026ndash;202. doi:10.1016/S0090-3019(02)00632-8\u003c/li\u003e\n \u003cli\u003eCalvarial tuberculosis in patient with cervical tuberculous lymphadenitis: a case report. Cureus. 2024. Available at: https://www.cureus.com/articles/194932\u003c/li\u003e\n \u003cli\u003eSkull base and calvarial tuberculosis: a rare presentation. Clin Radiol. 2020. Available at: https://www.sciencedirect.com/science/article/pii/S0019570720300111\u003c/li\u003e\n \u003cli\u003eCalvarial tuberculosis: an unusual presentation. BMJ Case Rep. 2019;12(4):e226967. doi:10.1136/bcr-2018-226967\u003c/li\u003e\n \u003cli\u003eMRI findings in spinal tuberculosis. Orthobullets. Available at: https://www.orthobullets.com/spine/2027/spinal-tuberculosis\u003c/li\u003e\n \u003cli\u003eAtypical spinal tuberculosis: a case report. Exp Ther Med. 2020;20(6):163. doi:10.3892/etm.2019.8014\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Calvarial tuberculosis, disseminated TB, spinal TB, psoas abscess, drug-resistant tuberculosis, vertebral osteolysis","lastPublishedDoi":"10.21203/rs.3.rs-6604450/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6604450/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eCalvarial tuberculosis (TB) is an uncommon manifestation of skeletal TB, and its progression to disseminated involvement of multiple systems is exceedingly rare. We report a unique case of a patient initially diagnosed with calvarial TB, who subsequently developed widespread involvement of the cervical and lumbar spine, bilateral paraspinal soft tissues, the right psoas muscle, and pulmonary parenchyma. Imaging studies demonstrated intraosseous abscesses, soft tissue masses, and compressive epidural components, consistent with disseminated TB. The patient was advised to undergo fluid aspiration for microbiological confirmation and drug susceptibility testing, in view of possible drug-resistant TB. This case underscores the need for high clinical suspicion, early diagnosis, and systemic evaluation in patients with skeletal TB to identify and manage potentially disseminated disease.\u003c/p\u003e","manuscriptTitle":"Extensive Multilevel Spinal and Extraspinal Involvement in a Case of Calvarial Tuberculosis: A Rare Disseminated Presentation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-02 07:06:38","doi":"10.21203/rs.3.rs-6604450/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e7489163-cea3-4395-9506-501e40e95e88","owner":[],"postedDate":"June 2nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-06-25T02:08:44+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-02 07:06:38","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6604450","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6604450","identity":"rs-6604450","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}