A 2-Year-Old Child with Progressive Headache, Nausea, and Personality Change

A 2-Year-Old Child with Progressive Headache, Nausea, and Personality Change | 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 Research Article A 2-Year-Old Child with Progressive Headache, Nausea, and Personality Change Emile Wogram, Ursula Feige, Roland Roelz, Marco Prinz, Horst Urbach, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8231681/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 18 Feb, 2026 Read the published version in Clinical Neuroradiology → Version 1 posted You are reading this latest preprint version Abstract This report belongs to a dedicated series on neuropathology–neuroimaging correlation. In keeping with the format of the series, the article is published without an abstract. Figures Figure 1 Figure 2 Figure 3 Figure 4 Case report A 2-year-old child presented with progressive headache, nausea, and personality changes which triggered cranial imaging and revealed a large right parietal mass lesion. Given the size and mass effect, urgent surgical resection was indicated. The patient was positioned supine with the head turned to the left. A parietal craniotomy including the central region was performed, and the dura was opened toward the sinus. A superficially well-demarcated mass was encountered, markedly compressing the underlying brain. Frozen section analysis was consistent with a malignant small-cell tumour, likely a primitive neuroectodermal tumour. Tumour boundaries were progressively defined. While the lesion was well separated from adjacent cortex superficially, deeper infiltration into parenchyma was evident. The resection proceeded in an extralesional, glioma-like fashion. Two compartments were identified: a soft, suctionable main tumour mass, and a firm component tightly adherent to the sinus. After delineating the dorsal circumference and falx level, resection proceeded anteriorly under cortical and subcortical stimulation. Subcortical stimulation up to 20 mA elicited no motor responses, permitting safe tumour removal with safety margins posteriorly to the corticospinal tract. The parenchymal component was completely resected; however, the firm portion adherent to the sinus could not be fully separated. Careful dissection allowed gradual thinning of this component down to the sinus wall, but complete (R0) resection was not feasible because of infiltration into the sinus wall. The infiltrated segment was coagulated as safely as possible and reinforced with a Duragen patch. Dural closure was achieved, the bone flap reattached, and layered wound closure completed. The postoperative course was uneventful, and on postoperative day 6 the child was discharged home in good general condition. Imaging The MRI on admission revealed an extensive space-occupying intraaxial lesion in the right parietal lobe (Figs. 1 and 2). The mass showed both solid components (Fig. 1 + 2; arrows) and cystic portions (Fig. 1a, arrowhead), accompanied by pronounced perifocal oedema (Fig. 1b, arrowhead). Diffusion-weighted imaging demonstrated marked diffusion restriction, suggestive of hypercellularity (not shown). On T1-weighted images, the solid components appeared hypointense on native scans (Fig. 2a, arrow), with strong gadolinium enhancement after contrast administration (Fig. 2b, arrow). No evidence of calcification or haemorrhage was detected. Differential Diagnosis Supratentorial, cortically based tumours with well-defined margins and diffusion restriction are rare in children ( 1 – 3 ). In patients older than 1.5 years, this radiologic appearance is most consistent with either an embryonal tumour or an ependymoma ( 4 ). High-grade gliomas are less likely because they typically demonstrate ill-defined margins: diffuse hemispheric glioma, H3G34-mutant, usually affects teenagers and young adults; paediatric diffuse high-grade glioma, H3 wild-type, IDH wild-type generally presents as a large supratentorial mass with poorly defined borders, often accompanied by haemorrhage and necrosis; and infant-type hemispheric glioma typically arises within the first year of life ( 4 ). Desmoplastic infantile glioma (DIG) and desmoplastic infantile astrocytoma (DIA) are low-grade tumours occurring in infants under 2 years, characterized by large cortically based cystic-solid masses with heterogeneous enhancement, calcifications, and variable diffusivity (4 + 5). These entities are unlikely in the present case given the patient’s age. Supratentorial Ependymal Tumour ZFTA (zinc finger translocation associated, previously known as C11orf95) fusion–positive ependymomas typically occur in children with a mean age of 7 years, whereas YAP1 fusion–positive tumours are less common and usually present within the first year of life. They manifest as large, well-delineated masses with thick, heterogeneous solid enhancement, prominent cystic components, central necrosis surrounded by calcifications and hemorrhage (the “periwinkle sign”), and associated peritumoural edema ( 4 ). Atypical Teratoid/Rhabdoid Tumour (ATRT) ATRT is a rare, highly malignant embryonal tumour (WHO grade 4) that predominantly affects children younger than 2 years. Neuroimaging typically reveals cystic components, thick and irregular enhancement of the cyst wall, marked surrounding edema, and a strong tendency for dissemination at diagnosis. Calcifications and diffusely low ADC values are also frequent findings ( 4 , 5 ). Embryonal Tumour with Multilayered Rosettes (ETMR) ETMR is an aggressive WHO grade 4 embryonal tumour that primarily arises in infants under 3 years of age, with no clear sex predilection ( 6 , 7 ) or a slight female predominance (59%, 2). Approximately 70% occur in supratentorial locations, although other sites have been reported ( 2 , 7 ). These tumours are usually large and well demarcated. Notably, ETMRs often exhibit little to no enhancement and relatively limited peritumoural edema compared with their size ( 4 ). On MRI, they demonstrate heterogeneous signal intensity with frequent diffusion restriction, cystic areas, and intratumoural hemorrhage ( 8 ). Imaging features overlap with other CNS embryonal tumours, but ETMRs tend to have very large volumes (mean 115 cm³), often spanning multiple lobes ( 9 ). Clinically, they behave aggressively with rapid progression despite intensive therapy. Local recurrence is most common, although leptomeningeal dissemination is frequent and rare extracranial relapses have been reported ( 10 , 11 ). CNS Neuroblastoma, FOXR2-Activated This large embryonal tumour typically presents in the first decade of life (mean age 5 years) and demonstrates cystic and/or necrotic components, heterogeneous enhancement, calcifications, and low mean ADC values ( 4 ). With early and adequate treatment, prognosis can be relatively favorable ( 3 ). CNS Tumours with BCOR Internal Tandem Duplication These WHO grade 4 tumours typically arise in early childhood (median age 3.5 years). Imaging shows large cortical masses with reduced diffusivity, variable signal heterogeneity, and poor contrast enhancement, often with central necrosis, hemorrhage, and calcifications. Prominent central veins within the tumour are a characteristic feature ( 12 ). Like ETMR, these tumours occur in very young children and share overlapping imaging features, including the relative absence of peripheral edema ( 4 ). Histology, Immunohistochemistry and Molecular Pathology In haematoxylin–eosin (H&E)-stained sections of formalin-fixed, paraffin-embedded biopsy material, a tumour with increased cellularity was evident. It predominantly showed neuropil-rich areas interspersed with dense tumour-cell aggregates forming multilayered rosettes (Fig. 3a + b). These rosettes consisted of embryonal cells arranged as pseudostratified neuroepithelium surrounding a central lumen. Cells adjacent to the lumen displayed a defined apical surface, with nuclei located basally, away from the lumen (Fig. 3c). Focal regions of fresh haemorrhage were also present. Immunohistochemistry demonstrated rosettes and tubular structures strongly positive for vimentin (Fig. 4a). Glial cell elements within the neuropil stained positively for GFAP (Fig. 4b). Nuclear expression of INI1 was retained (Fig. 4c). The proliferation marker MIB-1 revealed a high proliferative index of up to 80% (Fig. 4d). DNA methylation profiling classified the tumour as ETMR, showing gains on chromosome 2 and focal amplification of chromosome 19q (Fig. 4e). The calibrated score was 0.99983 for the methylation class “embryonal tumour with multilayered rosettes, C19MC-altered”, according to the Brain Tumour Classifier (version 12.8), where a score ≥ 0.9 indicates a robust match. Diagnosis Embryonal tumour with multilayered rosettes (ETMR), CNS WHO Grade 4 ETMR is a highly aggressive embryonal neoplasm of the CNS. Three morphological patterns are recognized: embryonal tumour with abundant neuropil and true rosettes, ependymoblastoma, and medulloepithelioma ( 13 ). The embryonal components, including rosettes and tubular structures, typically show strong immunoreactivity for nestin and vimentin ( 13 – 15 ). Approximately 90% of ETMRs harbor C19MC alterations at chromosome 19q13.42 ( 6 , 16 ), while ~ 5% are associated with DICER1 mutations ( 17 ). Diagnostic confirmation requires identification of an embryonal CNS tumour with one of the characteristic ETMR histological patterns, together with either C19MC alteration, DICER1 mutation, or, in unresolved cases, a DNA methylation profile consistent with ETMR. Although most ETMRs are intracranial, with 45% arising in non-hemispheric sites, spinal cord cases are rare ( 13 ). Reliable epidemiological data are lacking, but CNS embryonal tumours overall—previously grouped under the designation CNS-PNET—are diagnosed in roughly 1 per 700,000 children aged 0–4 years ( 7 , 18 ). Important differential diagnoses include other embryonal tumours such as atypical teratoid/rhabdoid tumour (ATRT) and medulloblastoma, which differ in histology and immunophenotype, as well as rare entities like intraocular medulloepithelioma and sacrococcygeal ependymoblastoma. These latter tumours share some histopathological features with ETMR but exhibit distinct molecular alterations and are therefore considered separate entities ( 13 ). The prognosis of ETMR is poor due to its rapid growth. Median survival is approximately 12 months despite multimodal therapy. Aggressive management with gross total resection, radiotherapy, and high-dose chemotherapy may prolong survival in selected cases ( 13 , 19 ). Figure Legends Figure 1. Axial T2-weighted MR images (a) showed a large right parietal lesion with a solid component (arrow) adjacent to cystic portions (arrowhead). On sagittal fluid-attenuated inversion recovery (FLAIR) images (b) the lesion appears isointense compared to the cerebral cortex (arrow). Surrounding perifocal edema is evident (arrowhead). Figure 2. Axial pre-contrast T1-weighted MR images revealed a hypointense signal of the solid tumour components (arrow). Axial T1 weighted images after gadolinium administration (b), showed marked contrast enhancement of the solid tumour portion. Figure 3. Haematoxylin-eosin-stained (H&E) section depicting multilayered rosettes, which is a defining feature of Embryonal tumour with multilayered rosettes (ETMR). The lumen of the rosette is indicated by an asterisk, the black circle indicates the surrounding neuropil (a). Another H&E stained section with abundant tumour surrounding neuropil (b). Scale bars: 200µm. Higher magnification of a H&E stained section featuring a multilayered rosette. The lumen of the rosette is indicated by an asterisk. Scale bar: 100µm. Figure 4. The embryonal component of the tumour shows a strong positivity in the immunohistochemistry against vimentin. The lumen of a multilayered rosette is indicated by an asterisk (a). Scale bar: 200µm. The neuropil surrounding the embryonal component of the tumour shows a glial cell elements that strongly react in the immunohistochemistry against GFAP (b). The embryonal component of the tumour exhibits a strong positivity in the immunohistochemistry against Ini-1 (c). The proliferation marker MIB-1 indicates a high proliferation rate of the tumour (d). Scale bars d-e: 100µm. DNA methylation profile (e) with alterations of a microRNA cluster on chromosome 19q13.42 (C19M, indicated by an asterisk). Declarations Conflict of interests: xy1-xy7 declare that they have no conflict of interests. Ethical standards: All investigations described in this manuscript were carried out with the approval of the responsible ethics committee and in accordance with national law and the Helsinki Declaration of 1975 (in its current revised form). Informed consent was obtained from the patient’s parents in this case if identifiable from pictures or other information within the manuscript. Consent to participate and consent to publish: Informed consent was obtained from the patient’s parents in this case if identifiable from pictures or other information within the manuscript. Author Contribution E.W., U.F., R.R.,D.E., and C.A.T. wrote the main manuscript text and E.W., U.F., D.E., and C.A.T. prepared the figures. All authors reviewed the manuscript. References McNamara C, Mankad K, Thust S, Dixon L, Limback-Stanic C, D’Arco F, et al. 2021 WHO classification of tumours of the central nervous system: a review for the neuroradiologist. Neuroradiology. 2022;64(10):1919–50. Khan S, Solano-Paez P, Suwal T, Lu M, Al-Karmi S, Ho B, et al. Clinical phenotypes and prognostic features of embryonal tumours with multi-layered rosettes: a rare brain tumour registry study. Lancet Child Adolesc Health. 2021;5(11):800–13. Schepke E, Löfgren M, Pietsch T, Kling T, Nordborg C, Olsson Bontell T, et al. Supratentorial CNS-PNETs in children; a Swedish population-based study with molecular re-evaluation and long-term follow-up. Clin Epigenetics. 2023;15:40. Rameh V, Löbel U, D’Arco F, Bhatia A, Mankad K, Poussaint TY, et al. Cortically based brain tumours in children: A decision-tree approach in the radiology reading room. AJNR Am J Neuroradiol. 2025;46:11–23. Koelsche C, Sahm F, Paulus W, Mittelbronn M, Giangaspero F, Antonelli M, et al. BRAF V600E expression and distribution in desmoplastic infantile astrocytoma/ganglioglioma. Neuropathol Appl Neurobiol. 2014;40(3):337–44. Lambo S, Gröbner SN, Rausch T, Waszak SM, Schmidt C, Gorthi A, et al. The molecular landscape of ETMR at diagnosis and relapse. Nature. 2019;576:274–80. Lambo S, von Hoff K, Korshunov A, Pfister SM, Kool M. ETMR: a tumour entity in its infancy. Acta Neuropathol. 2020;140:249–66. Nowak J, Seidel C, Berg F, Pietsch T, Friedrich C, von Hoff K, et al. MRI characteristics of ependymoblastoma: results from 22 centrally reviewed cases. AJNR Am J Neuroradiol. 2014;35(10):1996–2001. Nowak J, Seidel C, Pietsch T, Alkonyi B, Fuss TL, Friedrich C, et al. Systematic comparison of MRI findings in pediatric ependymoblastoma with ependymoma and CNS primitive neuroectodermal tumour NOS. Neuro Oncol. 2015;17(8):1157–65. Korshunov A, Sturm D, Ryzhova M, Hovestadt V, Gessi M, Jones DTW, et al. Embryonal tumour with abundant neuropil and true rosettes (ETANTR), ependymoblastoma, and medulloepithelioma share molecular similarity and comprise a single entity. Acta Neuropathol. 2014;128(2):279–89. Shah AH, Khatib Z, Niazi T. Extracranial extra-CNS spread of embryonal tumour with multilayered rosettes (ETMR): case series and systematic review. Childs Nerv Syst. 2018;34(4):649–54. Cardoen L, Tauziède-Espariat A, Dangouloff-Ros V, Moalla S, Nicolas N, Roux CJ, et al. Imaging features with histopathologic correlation of CNS high-grade neuroepithelial tumours with a BCOR internal tandem duplication. AJNR Am J Neuroradiol. 2022;43(1):151–6. WHO Classification of Tumours Editorial Board. Central nervous system tumours. 5th ed. Lyon: International Agency for Research on Cancer; 2021 Eberhart CG, Brat DJ, Cohen KJ, Burger PC. Pediatric neuroblastic brain tumours containing abundant neuropil and true rosettes. Pediatr Dev Pathol. 2000;3(4):346–52. Gessi M, Giangaspero F, Lauriola L, Gardiman M, Scheithauer BW, Halliday W, et al. Embryonal tumours with abundant neuropil and true rosettes: a distinctive CNS PNET. Am J Surg Pathol. 2009;33(2):211–7. Kleinman CL, Gerges N, Papillon-Cavanagh S, Sin-Chan P, Pramatarova A, Quang DA, et al. Fusion of TTYH1 with the C19MC microRNA cluster drives DNMT3B isoform expression in ETMR. Nat Genet. 2014;46(1):39–44. de Kock L, Priest JR, Foulkes WD, Alexandrescu S. An update on the CNS manifestations of DICER1 syndrome. Acta Neuropathol. 2020;139(4):689–701. Ostrom QT, Cioffi G, Gittleman H, Patil N, Waite K, Kruchko C, et al. CBTRUS Statistical Report: Primary Brain and Other CNS Tumours Diagnosed in the US in 2012–2016. Neuro Oncol. 2019;21(Suppl 5):v1-100. Jaramillo S, Grosshans DR, Philip N, Varan A, Akyuz C, McAleer MF, et al. Radiation for ETMR: Literature review and case series of patients treated with proton therapy. Clin Transl Radiat Oncol. 2019;15:31–7. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 18 Feb, 2026 Read the published version in Clinical Neuroradiology → 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. 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11:43:00","extension":"png","order_by":37,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":130922,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFig4d.png","url":"https://assets-eu.researchsquare.com/files/rs-8231681/v1/752ebefe0194297ee771cb8d.png"},{"id":97345223,"identity":"f6bad0fa-b53a-4539-8ee6-b4eb017c1c1a","added_by":"auto","created_at":"2025-12-03 11:43:00","extension":"png","order_by":38,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":38960,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFig4e.png","url":"https://assets-eu.researchsquare.com/files/rs-8231681/v1/7743790ad9ca10d5e3625538.png"},{"id":97345219,"identity":"084a04b0-c403-4640-b624-3670791104d7","added_by":"auto","created_at":"2025-12-03 11:43:00","extension":"xml","order_by":39,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":48216,"visible":true,"origin":"","legend":"","description":"","filename":"0311cb47086f435f8ad8f6f9527ddf7b1structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8231681/v1/9f62bb5c26cb4b0f509dfa5b.xml"},{"id":97370448,"identity":"32e66ac6-4de0-4625-b4f5-a271ff9a256e","added_by":"auto","created_at":"2025-12-03 16:27:24","extension":"html","order_by":40,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":54241,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8231681/v1/494e55a27e1c405070a2dfb9.html"},{"id":97345188,"identity":"c315f823-9479-48f4-bc34-56813d29265f","added_by":"auto","created_at":"2025-12-03 11:42:59","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":189627,"visible":true,"origin":"","legend":"\u003cp\u003eAxial T2-weighted MR images (a) showed a large right parietal lesion with a solid component (arrow) adjacent to cystic portions (arrowhead). On sagittal fluid-attenuated inversion recovery (FLAIR) images (b) the lesion appears isointense compared to the cerebral cortex (arrow). Surrounding perifocal edema is evident (arrowhead).\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8231681/v1/69ff7879cc60c32bff7489a6.jpg"},{"id":97371004,"identity":"fa00b67a-160f-4e1c-8e6c-2dcca2035486","added_by":"auto","created_at":"2025-12-03 16:28:15","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":453913,"visible":true,"origin":"","legend":"\u003cp\u003eAxial pre-contrast T1-weighted MR images revealed a hypointense signal of the solid tumour components (arrow). Axial T1 weighted images after gadolinium administration (b), showed marked contrast enhancement of the solid tumour portion.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8231681/v1/afa3451d1381f09c382a6266.png"},{"id":97345194,"identity":"3c13e4e0-5d50-4539-9c75-45a7ca4ad905","added_by":"auto","created_at":"2025-12-03 11:42:59","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":3979581,"visible":true,"origin":"","legend":"\u003cp\u003eHaematoxylin-eosin-stained (H\u0026amp;E) section depicting multilayered rosettes, which is a defining feature of Embryonal tumour with multilayered rosettes (ETMR). The lumen of the rosette is indicated by an asterisk, the black circle indicates the surrounding neuropil (a). Another H\u0026amp;E stained section with abundant tumour surrounding neuropil (b). Scale bars: 200µm. Higher magnification of a H\u0026amp;E stained section featuring a multilayered rosette. The lumen of the rosette is indicated by an asterisk. Scale bar: 100µm.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8231681/v1/06b2292dc3334a8f76590e75.png"},{"id":97345196,"identity":"365ce5c1-5169-48a8-9b00-7720d5c50937","added_by":"auto","created_at":"2025-12-03 11:42:59","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":5908124,"visible":true,"origin":"","legend":"\u003cp\u003eThe embryonal component of the tumour shows a strong positivity in the immunohistochemistry against vimentin. The lumen of a multilayered rosette is indicated by an asterisk (a). Scale bar: 200µm. The neuropil surrounding the embryonal component of the tumour shows a glial cell elements that strongly react in the immunohistochemistry against GFAP (b). The embryonal component of the tumour exhibits a strong positivity in the immunohistochemistry against Ini-1 (c). The proliferation marker MIB-1 indicates a high proliferation rate of the tumour (d). Scale bars d-e: 100µm. DNA methylation profile (e) with alterations of a microRNA cluster on chromosome 19q13.42 (C19M, indicated by an asterisk).\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-8231681/v1/9922a23b2186660258e625e8.png"},{"id":103251364,"identity":"a60a0681-6f27-4c08-b159-f6a1652a923f","added_by":"auto","created_at":"2026-02-23 16:08:22","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":13681634,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8231681/v1/4871889d-5d3a-4d70-8187-587e1d1a0dc1.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A 2-Year-Old Child with Progressive Headache, Nausea, and Personality Change","fulltext":[{"header":"Case report","content":"\u003cp\u003eA 2-year-old child presented with progressive headache, nausea, and personality changes which triggered cranial imaging and revealed a large right parietal mass lesion. Given the size and mass effect, urgent surgical resection was indicated.\u003c/p\u003e\u003cp\u003eThe patient was positioned supine with the head turned to the left. A parietal craniotomy including the central region was performed, and the dura was opened toward the sinus.\u003c/p\u003e\u003cp\u003eA superficially well-demarcated mass was encountered, markedly compressing the underlying brain. Frozen section analysis was consistent with a malignant small-cell tumour, likely a primitive neuroectodermal tumour. Tumour boundaries were progressively defined. While the lesion was well separated from adjacent cortex superficially, deeper infiltration into parenchyma was evident. The resection proceeded in an extralesional, glioma-like fashion. Two compartments were identified: a soft, suctionable main tumour mass, and a firm component tightly adherent to the sinus. After delineating the dorsal circumference and falx level, resection proceeded anteriorly under cortical and subcortical stimulation. Subcortical stimulation up to 20 mA elicited no motor responses, permitting safe tumour removal with safety margins posteriorly to the corticospinal tract.\u003c/p\u003e\u003cp\u003eThe parenchymal component was completely resected; however, the firm portion adherent to the sinus could not be fully separated. Careful dissection allowed gradual thinning of this component down to the sinus wall, but complete (R0) resection was not feasible because of infiltration into the sinus wall. The infiltrated segment was coagulated as safely as possible and reinforced with a Duragen patch. Dural closure was achieved, the bone flap reattached, and layered wound closure completed. The postoperative course was uneventful, and on postoperative day 6 the child was discharged home in good general condition.\u003c/p\u003e"},{"header":"Imaging","content":"\u003cp\u003eThe MRI on admission revealed an extensive space-occupying intraaxial lesion in the right parietal lobe (Figs.\u0026nbsp;1 and 2). The mass showed both solid components (Fig.\u0026nbsp;1 + 2; arrows) and cystic portions (Fig.\u0026nbsp;1a, arrowhead), accompanied by pronounced perifocal oedema (Fig.\u0026nbsp;1b, arrowhead). Diffusion-weighted imaging demonstrated marked diffusion restriction, suggestive of hypercellularity (not shown). On T1-weighted images, the solid components appeared hypointense on native scans (Fig.\u0026nbsp;2a, arrow), with strong gadolinium enhancement after contrast administration (Fig.\u0026nbsp;2b, arrow). No evidence of calcification or haemorrhage was detected.\u003c/p\u003e"},{"header":"Differential Diagnosis","content":"\u003cp\u003eSupratentorial, cortically based tumours with well-defined margins and diffusion restriction are rare in children (\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e–\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). In patients older than 1.5 years, this radiologic appearance is most consistent with either an embryonal tumour or an ependymoma (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). High-grade gliomas are less likely because they typically demonstrate ill-defined margins: diffuse hemispheric glioma, H3G34-mutant, usually affects teenagers and young adults; paediatric diffuse high-grade glioma, H3 wild-type, IDH wild-type generally presents as a large supratentorial mass with poorly defined borders, often accompanied by haemorrhage and necrosis; and infant-type hemispheric glioma typically arises within the first year of life (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Desmoplastic infantile glioma (DIG) and desmoplastic infantile astrocytoma (DIA) are low-grade tumours occurring in infants under 2 years, characterized by large cortically based cystic-solid masses with heterogeneous enhancement, calcifications, and variable diffusivity (4 + 5). These entities are unlikely in the present case given the patient’s age.\u003c/p\u003e\n\u003ch3\u003eSupratentorial Ependymal Tumour\u003c/h3\u003e\n\u003cp\u003eZFTA (zinc finger translocation associated, previously known as C11orf95) fusion\u0026ndash;positive ependymomas typically occur in children with a mean age of 7 years, whereas YAP1 fusion\u0026ndash;positive tumours are less common and usually present within the first year of life. They manifest as large, well-delineated masses with thick, heterogeneous solid enhancement, prominent cystic components, central necrosis surrounded by calcifications and hemorrhage (the \u0026ldquo;periwinkle sign\u0026rdquo;), and associated peritumoural edema (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\n\u003ch3\u003eAtypical Teratoid/Rhabdoid Tumour (ATRT)\u003c/h3\u003e\n\u003cp\u003eATRT is a rare, highly malignant embryonal tumour (WHO grade 4) that predominantly affects children younger than 2 years. Neuroimaging typically reveals cystic components, thick and irregular enhancement of the cyst wall, marked surrounding edema, and a strong tendency for dissemination at diagnosis. Calcifications and diffusely low ADC values are also frequent findings (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\n\u003ch3\u003eEmbryonal Tumour with Multilayered Rosettes (ETMR)\u003c/h3\u003e\n\u003cp\u003eETMR is an aggressive WHO grade 4 embryonal tumour that primarily arises in infants under 3 years of age, with no clear sex predilection (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) or a slight female predominance (59%, 2). Approximately 70% occur in supratentorial locations, although other sites have been reported (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). These tumours are usually large and well demarcated. Notably, ETMRs often exhibit little to no enhancement and relatively limited peritumoural edema compared with their size (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). On MRI, they demonstrate heterogeneous signal intensity with frequent diffusion restriction, cystic areas, and intratumoural hemorrhage (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Imaging features overlap with other CNS embryonal tumours, but ETMRs tend to have very large volumes (mean 115 cm\u0026sup3;), often spanning multiple lobes (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Clinically, they behave aggressively with rapid progression despite intensive therapy. Local recurrence is most common, although leptomeningeal dissemination is frequent and rare extracranial relapses have been reported (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e\n\u003ch3\u003eCNS Neuroblastoma, FOXR2-Activated\u003c/h3\u003e\n\u003cp\u003eThis large embryonal tumour typically presents in the first decade of life (mean age 5 years) and demonstrates cystic and/or necrotic components, heterogeneous enhancement, calcifications, and low mean ADC values (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). With early and adequate treatment, prognosis can be relatively favorable (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eCNS Tumours with BCOR Internal Tandem Duplication\u003c/h2\u003e\u003cp\u003eThese WHO grade 4 tumours typically arise in early childhood (median age 3.5 years). Imaging shows large cortical masses with reduced diffusivity, variable signal heterogeneity, and poor contrast enhancement, often with central necrosis, hemorrhage, and calcifications. Prominent central veins within the tumour are a characteristic feature (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Like ETMR, these tumours occur in very young children and share overlapping imaging features, including the relative absence of peripheral edema (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e"},{"header":"Histology, Immunohistochemistry and Molecular Pathology","content":"\u003cp\u003eIn haematoxylin\u0026ndash;eosin (H\u0026amp;E)-stained sections of formalin-fixed, paraffin-embedded biopsy material, a tumour with increased cellularity was evident. It predominantly showed neuropil-rich areas interspersed with dense tumour-cell aggregates forming multilayered rosettes (Fig.\u0026nbsp;3a\u0026thinsp;+\u0026thinsp;b). These rosettes consisted of embryonal cells arranged as pseudostratified neuroepithelium surrounding a central lumen. Cells adjacent to the lumen displayed a defined apical surface, with nuclei located basally, away from the lumen (Fig.\u0026nbsp;3c). Focal regions of fresh haemorrhage were also present.\u003c/p\u003e\u003cp\u003eImmunohistochemistry demonstrated rosettes and tubular structures strongly positive for vimentin (Fig.\u0026nbsp;4a). Glial cell elements within the neuropil stained positively for GFAP (Fig.\u0026nbsp;4b). Nuclear expression of INI1 was retained (Fig.\u0026nbsp;4c). The proliferation marker MIB-1 revealed a high proliferative index of up to 80% (Fig.\u0026nbsp;4d).\u003c/p\u003e\u003cp\u003eDNA methylation profiling classified the tumour as ETMR, showing gains on chromosome 2 and focal amplification of chromosome 19q (Fig.\u0026nbsp;4e). The calibrated score was 0.99983 for the methylation class \u0026ldquo;embryonal tumour with multilayered rosettes, C19MC-altered\u0026rdquo;, according to the Brain Tumour Classifier (version 12.8), where a score\u0026thinsp;\u0026ge;\u0026thinsp;0.9 indicates a robust match.\u003c/p\u003e\n\u003ch3\u003eDiagnosis\u003c/h3\u003e\n\u003cp\u003eEmbryonal tumour with multilayered rosettes (ETMR), CNS WHO Grade 4\u003c/p\u003e\u003cp\u003eETMR is a highly aggressive embryonal neoplasm of the CNS. Three morphological patterns are recognized: embryonal tumour with abundant neuropil and true rosettes, ependymoblastoma, and medulloepithelioma (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). The embryonal components, including rosettes and tubular structures, typically show strong immunoreactivity for nestin and vimentin (\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Approximately 90% of ETMRs harbor C19MC alterations at chromosome 19q13.42 (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e), while\u0026thinsp;~\u0026thinsp;5% are associated with DICER1 mutations (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Diagnostic confirmation requires identification of an embryonal CNS tumour with one of the characteristic ETMR histological patterns, together with either C19MC alteration, DICER1 mutation, or, in unresolved cases, a DNA methylation profile consistent with ETMR.\u003c/p\u003e\u003cp\u003eAlthough most ETMRs are intracranial, with 45% arising in non-hemispheric sites, spinal cord cases are rare (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Reliable epidemiological data are lacking, but CNS embryonal tumours overall\u0026mdash;previously grouped under the designation CNS-PNET\u0026mdash;are diagnosed in roughly 1 per 700,000 children aged 0\u0026ndash;4 years (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eImportant differential diagnoses include other embryonal tumours such as atypical teratoid/rhabdoid tumour (ATRT) and medulloblastoma, which differ in histology and immunophenotype, as well as rare entities like intraocular medulloepithelioma and sacrococcygeal ependymoblastoma. These latter tumours share some histopathological features with ETMR but exhibit distinct molecular alterations and are therefore considered separate entities (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe prognosis of ETMR is poor due to its rapid growth. Median survival is approximately 12 months despite multimodal therapy. Aggressive management with gross total resection, radiotherapy, and high-dose chemotherapy may prolong survival in selected cases (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cb\u003eFigure Legends\u003c/b\u003e\u003c/p\u003e\u003cp\u003eFigure 1. Axial T2-weighted MR images (a) showed a large right parietal lesion with a solid component (arrow) adjacent to cystic portions (arrowhead). On sagittal fluid-attenuated inversion recovery (FLAIR) images (b) the lesion appears isointense compared to the cerebral cortex (arrow). Surrounding perifocal edema is evident (arrowhead).\u003c/p\u003e\u003cp\u003eFigure 2. Axial pre-contrast T1-weighted MR images revealed a hypointense signal of the solid tumour components (arrow). Axial T1 weighted images after gadolinium administration (b), showed marked contrast enhancement of the solid tumour portion.\u003c/p\u003e\u003cp\u003eFigure 3. Haematoxylin-eosin-stained (H\u0026amp;E) section depicting multilayered rosettes, which is a defining feature of Embryonal tumour with multilayered rosettes (ETMR). The lumen of the rosette is indicated by an asterisk, the black circle indicates the surrounding neuropil (a). Another H\u0026amp;E stained section with abundant tumour surrounding neuropil (b). Scale bars: 200\u0026micro;m. Higher magnification of a H\u0026amp;E stained section featuring a multilayered rosette. The lumen of the rosette is indicated by an asterisk. Scale bar: 100\u0026micro;m.\u003c/p\u003e\u003cp\u003eFigure 4. The embryonal component of the tumour shows a strong positivity in the immunohistochemistry against vimentin. The lumen of a multilayered rosette is indicated by an asterisk (a). Scale bar: 200\u0026micro;m. The neuropil surrounding the embryonal component of the tumour shows a glial cell elements that strongly react in the immunohistochemistry against GFAP (b). The embryonal component of the tumour exhibits a strong positivity in the immunohistochemistry against Ini-1 (c). The proliferation marker MIB-1 indicates a high proliferation rate of the tumour (d). Scale bars d-e: 100\u0026micro;m. DNA methylation profile (e) with alterations of a microRNA cluster on chromosome 19q13.42 (C19M, indicated by an asterisk).\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eConflict of interests: xy1-xy7 declare that they have no conflict of interests.\u003c/p\u003e\n\u003cp\u003eEthical standards: All investigations described in this manuscript were carried out with the approval of the responsible ethics committee and in accordance with national law and the Helsinki Declaration of 1975 (in its current revised form). Informed consent was obtained from the patient’s parents in this case if identifiable from pictures or other information within the manuscript.\u003c/p\u003e\n\u003cp\u003eConsent to participate and consent to publish: Informed consent was obtained from the patient’s parents in this case if identifiable from pictures or other information within the manuscript.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eE.W., U.F., R.R.,D.E., and C.A.T. wrote the main manuscript text and E.W., U.F., D.E., and C.A.T. prepared the figures. All authors reviewed the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMcNamara C, Mankad K, Thust S, Dixon L, Limback-Stanic C, D\u0026rsquo;Arco F, et al. 2021 WHO classification of tumours of the central nervous system: a review for the neuroradiologist. Neuroradiology. 2022;64(10):1919\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKhan S, Solano-Paez P, Suwal T, Lu M, Al-Karmi S, Ho B, et al. Clinical phenotypes and prognostic features of embryonal tumours with multi-layered rosettes: a rare brain tumour registry study. Lancet Child Adolesc Health. 2021;5(11):800\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSchepke E, L\u0026ouml;fgren M, Pietsch T, Kling T, Nordborg C, Olsson Bontell T, et al. Supratentorial CNS-PNETs in children; a Swedish population-based study with molecular re-evaluation and long-term follow-up. Clin Epigenetics. 2023;15:40.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRameh V, L\u0026ouml;bel U, D\u0026rsquo;Arco F, Bhatia A, Mankad K, Poussaint TY, et al. Cortically based brain tumours in children: A decision-tree approach in the radiology reading room. AJNR Am J Neuroradiol. 2025;46:11\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKoelsche C, Sahm F, Paulus W, Mittelbronn M, Giangaspero F, Antonelli M, et al. BRAF V600E expression and distribution in desmoplastic infantile astrocytoma/ganglioglioma. Neuropathol Appl Neurobiol. 2014;40(3):337\u0026ndash;44.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLambo S, Gr\u0026ouml;bner SN, Rausch T, Waszak SM, Schmidt C, Gorthi A, et al. The molecular landscape of ETMR at diagnosis and relapse. Nature. 2019;576:274\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLambo S, von Hoff K, Korshunov A, Pfister SM, Kool M. ETMR: a tumour entity in its infancy. Acta Neuropathol. 2020;140:249\u0026ndash;66.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNowak J, Seidel C, Berg F, Pietsch T, Friedrich C, von Hoff K, et al. MRI characteristics of ependymoblastoma: results from 22 centrally reviewed cases. AJNR Am J Neuroradiol. 2014;35(10):1996\u0026ndash;2001.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNowak J, Seidel C, Pietsch T, Alkonyi B, Fuss TL, Friedrich C, et al. Systematic comparison of MRI findings in pediatric ependymoblastoma with ependymoma and CNS primitive neuroectodermal tumour NOS. Neuro Oncol. 2015;17(8):1157\u0026ndash;65.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKorshunov A, Sturm D, Ryzhova M, Hovestadt V, Gessi M, Jones DTW, et al. Embryonal tumour with abundant neuropil and true rosettes (ETANTR), ependymoblastoma, and medulloepithelioma share molecular similarity and comprise a single entity. Acta Neuropathol. 2014;128(2):279\u0026ndash;89.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eShah AH, Khatib Z, Niazi T. Extracranial extra-CNS spread of embryonal tumour with multilayered rosettes (ETMR): case series and systematic review. Childs Nerv Syst. 2018;34(4):649\u0026ndash;54.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCardoen L, Tauzi\u0026egrave;de-Espariat A, Dangouloff-Ros V, Moalla S, Nicolas N, Roux CJ, et al. Imaging features with histopathologic correlation of CNS high-grade neuroepithelial tumours with a BCOR internal tandem duplication. AJNR Am J Neuroradiol. 2022;43(1):151\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWHO Classification of Tumours Editorial Board. Central nervous system tumours. 5th ed. Lyon: International Agency for Research on Cancer; 2021\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEberhart CG, Brat DJ, Cohen KJ, Burger PC. Pediatric neuroblastic brain tumours containing abundant neuropil and true rosettes. Pediatr Dev Pathol. 2000;3(4):346\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGessi M, Giangaspero F, Lauriola L, Gardiman M, Scheithauer BW, Halliday W, et al. Embryonal tumours with abundant neuropil and true rosettes: a distinctive CNS PNET. Am J Surg Pathol. 2009;33(2):211\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKleinman CL, Gerges N, Papillon-Cavanagh S, Sin-Chan P, Pramatarova A, Quang DA, et al. Fusion of TTYH1 with the C19MC microRNA cluster drives DNMT3B isoform expression in ETMR. Nat Genet. 2014;46(1):39\u0026ndash;44.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ede Kock L, Priest JR, Foulkes WD, Alexandrescu S. An update on the CNS manifestations of DICER1 syndrome. Acta Neuropathol. 2020;139(4):689\u0026ndash;701.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOstrom QT, Cioffi G, Gittleman H, Patil N, Waite K, Kruchko C, et al. CBTRUS Statistical Report: Primary Brain and Other CNS Tumours Diagnosed in the US in 2012\u0026ndash;2016. Neuro Oncol. 2019;21(Suppl 5):v1-100.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJaramillo S, Grosshans DR, Philip N, Varan A, Akyuz C, McAleer MF, et al. Radiation for ETMR: Literature review and case series of patients treated with proton therapy. Clin Transl Radiat Oncol. 2019;15:31\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":true,"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":"","lastPublishedDoi":"10.21203/rs.3.rs-8231681/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8231681/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"This report belongs to a dedicated series on neuropathology–neuroimaging correlation. In keeping with the format of the series, the article is published without an abstract.","manuscriptTitle":"A 2-Year-Old Child with Progressive Headache, Nausea, and Personality Change","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-03 11:42:54","doi":"10.21203/rs.3.rs-8231681/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":"2d275db9-0bd1-442c-93bc-a95e00256245","owner":[],"postedDate":"December 3rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-02-23T16:05:04+00:00","versionOfRecord":{"articleIdentity":"rs-8231681","link":"https://doi.org/10.1007/s00062-026-01622-y","journal":{"identity":"clinical-neuroradiology","isVorOnly":false,"title":"Clinical Neuroradiology"},"publishedOn":"2026-02-18 15:59:36","publishedOnDateReadable":"February 18th, 2026"},"versionCreatedAt":"2025-12-03 11:42:54","video":"","vorDoi":"10.1007/s00062-026-01622-y","vorDoiUrl":"https://doi.org/10.1007/s00062-026-01622-y","workflowStages":[]},"version":"v1","identity":"rs-8231681","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8231681","identity":"rs-8231681","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}