A Rare Case of Anti-Yo Positive Paraneoplastic Limbic Encephalitis Associated with Thyroid– Parathyroid Adenoma

A Rare Case of Anti-Yo Positive Paraneoplastic Limbic Encephalitis Associated with Thyroid– Parathyroid Adenoma | 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 Case Report A Rare Case of Anti-Yo Positive Paraneoplastic Limbic Encephalitis Associated with Thyroid– Parathyroid Adenoma Ezgi Aslan, Asuman Orhan Varoglu, Begumhan Baysal, Mehmet Tarik Tatoglu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8304270/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 19 Jan, 2026 Read the published version in The Cerebellum → Version 1 posted 7 You are reading this latest preprint version Abstract Objective Paraneoplastic neurological syndromes (PNS) are typically associated with malignant neoplasms. The anti-Yo antibody is classically linked to paraneoplastic cerebellar degeneration; its coexistence with limbic encephalitis is extremely rare. We report the first case of anti-Yo–positive limbic encephalitis associated with a benign thyroid–parathyroid adenoma. Case Report: A 59-year-old male presented with epileptic seizures, left upper limb weakness, dysarthria, and confusion. Serum anti-Yo antibody was positive. Cranial MRI revealed diffusion restriction in the cerebellar hemispheres and middle cerebellar peduncles. PET-CT showed intense FDG uptake in the posterior right thyroid lobe. A fine-needle aspiration biopsy showed solid and cystic elements consistent with a parathyroid adenoma. The patient received high-dose intravenous methylprednisolone followed by intravenous immunoglobulin, resulting in clinical improvement. Conclusion This report presents the first documented association between anti-Yo–positive limbic encephalitis and a benign thyroid–parathyroid adenoma. It emphasizes the importance of early immunotherapy and multidisciplinary evaluation in rare paraneoplastic syndromes. Anti-Yo Antibodies Paraneoplastic Limbic Encephalitis Thyroid–Parathyroid Adenoma Autoimmunity Figures Figure 1 Figure 2 Introduction Immune-mediated neurological disorders are known as paraneoplastic neurological syndromes (PNS) associated with underlying neoplasms, independent of direct tumor invasion or metastasis [ 1 ]. Although they account for less than 10% of all paraneoplastic syndromes, PNS can cause severe neurological dysfunction. Limbic encephalitis (LE) presents with seizures, memory deficits, and behavioral or personality changes, often due to autoimmune or paraneoplastic mechanisms [ 2 ]. The anti-Yo (PCA-1) antibody is a well-known marker of paraneoplastic cerebellar degeneration, most commonly found in women with breast or ovarian malignancies [ 3 ]. Reports of anti-Yo–positive LE in males or in association with benign tumors are exceedingly rare [ 4 ]. To our knowledge, no prior study has described anti-Yo–associated limbic encephalitis secondary to a benign thyroid–parathyroid adenoma. This case aims to broaden the clinical spectrum of anti-Yo–related disorders and highlight the relevance of antineuronal antibody screening in atypical neurological presentations. Case Report A 59-year-old man was taken in for a 5-month complaint of epileptic seizures, tep-by-step lower limb weakness for two months, and recent onset of dysarthria and confusion. Neurological examination revealed mild somnolence, dysarthric speech, left upper limb distal weakness (− 5/5), lower limb weakness (4/5), bilateral flexor plantar responses, and a positive Hoffman sign on the left. Diffusion restriction was seen in the middle cerebellar peduncles and cerebellar hemispheres on cranial MRI. Additionally, FLAIR sequences show hyperintense gliotic signals in the centrum semiovale, corona radiata, and bilateral periventricular white matter (Fig. 1 ). Analysis of the cerebrospinal fluid (CSF) indicated increased protein 78 mg/dL (15–45 mg/dL) with negative cytology and pathogen PCR results. Serum testing revealed anti-Yo antibody positivity. MRI of the brain showed multiple diffusion restrictions in the cerebellar hemispheres, vermis, and middle cerebellar peduncles. PET-CT revealed a hypermetabolic lesion (25 × 17 mm) in the posterior aspect of the right thyroid lobe. Cystic and solid components compatible with parathyroid adenoma were found during a fine-needle aspiration biopsy. (Fig. 2 ). Immunohistochemistry revealed thyroid follicular cells positive for TTF-1 and negative for parathormone, confirming benign thyroidal degeneration. Intravenous methylprednisolone treatment consisted of followed by five days of intravenous immunoglobulin (IVIG). After therapy, muscle strength improved, gait ataxia regressed, and speech became intelligible. Discussion Anti-Yo antibodies are directed against Purkinje cell cytoplasmic antigens and are strongly associated with paraneoplastic cerebellar degeneration [ 3 ]. Limbic involvement, however, is rare and has been mainly reported in association with lung, prostate, or gastrointestinal adenocarcinomas [ 4 , 5 ]. The present case is remarkable for three reasons: [ 1 ] it occurred in a male patient, [ 2 ] it was associated with a benign thyroid–parathyroid adenoma, and [ 3 ] cerebellar and limbic involvement coexisted. This expands the recognized clinical and pathological spectrum of anti-Yo–associated disorders. While anti-Yo–positive PNS are often refractory to immunotherapy [ 7 ], our patient exhibited marked improvement following high-dose corticosteroids and IVIG. This supports the importance of early recognition and aggressive immunomodulatory therapy [ 8 ]. Additionally, this case suggests that benign tumors may also elicit paraneoplastic immune responses. Anti-Yo antibodies are not restricted to cerebellar systems but may also affect the limbic network. Clinicians should therefore consider paraneoplastic and autoimmune etiologies in unexplained encephalitic syndromes [ 9 , 10 ]. Conclusion This is the first documented case of anti-Yo–positive limbic encephalitis associated with a benign thyroid–parathyroid adenoma. Declarations Consent to Publish declaration : Written informed consent forms were obtained from the patients. Funding Declaration : No funds, grants, or other support were received—no conflict of interest. Author Contribution Conceptualization: AOV; Data curation: EA; Formal analysis: AOV; Funding acquisition: XXX; Investigation: AOV, EA; Methodology: AOV; Project administration: AOV; Resources: AOV; Software: XXX; Supervision: AOV, EA, BB, MTT; Validation: XXX; Visualization: BB, MTT; Writing - original draft: AOV, BB; Writing - review & editing: AOV, EA. Acknowledgement Asuman Orhan Varoglu M.D.Istanbul Medeniyet University, Medical FacultyDepartments of Neurology Istanbul, Turkey, Tel: +90 216 5664000 Fax: +90 216 5664023e-mail: [email protected] /08/2025We would like to submit a manuscript authored by Varoglu for consideration to be published in “The Cerebellum”. Our manuscript is titled “A Rare Case of Anti-Yo Positive Paraneoplastic Limbic Encephalitis Associated with Thyroid–Parathyroid Adenoma”. The manuscript has not been published, nor will be simultaneously submitted or published elsewhere. All co-authors have approved the manuscript in its current form for submission to “ The Cerebellum”. Thank you very much for your close attention. We are looking forward to hearing from you.Sincerely yours, Asuman Orhan Varoglu M.D Associate Professor of the Department of Neurology References Gultekin SH, Rosenfeld MR, Voltz R, et al. Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumour association in 50 patients. Brain. 2000;123(7):1481–94. 10.1093/brain/123.7.1481 . Coker RK, Doran RM, Moss RJ, et al. A case of limbic encephalitis presenting as a paraneoplastic manifestation of limited-stage small cell lung cancer: a case report. J Med Case Rep. 2010;4:408. 10.1186/1752-1947-4-408 . Furneaux HF, Rosenblum MK, Dalmau J, et al. Anti-Hu associated paraneoplastic limbic encephalitis. Dev Med Child Neurol. 2012;54(9):850–6. 10.1111/j.1469-8749.2012.04221.x . Giometto B, Grisold W, Vitaliani R, et al. Paraneoplastic limbic encephalitis: clinical findings and recommended diagnostic work-up. Arch Neurol. 2010;67(3):330–5. 10.1001/archneurol.2009.341 . Dubey D, Pittock SJ, Kelly CR, et al. Autoimmune encephalitis epidemiology and a comparison to infectious encephalitis. Ann Neurol. 2018;83(1):166–77. 10.1002/ana.25131 . Gultekin SH, Rosenfeld MR, Voltz R, Eichen J, Posner JB, Dalmau J. Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumour association in 50 patients. Brain. 2000;123(Pt 7):1481–94. 10.1093/brain/123.7.1481 . Komori T, Tanaka K, Murai H et al. Improvement of paraneoplastic limbic encephalitis after systemic treatment with rituximab in a patient with B-cell chronic lymphocytic leukemia. Case Rep Hematol. 2013; 2013:958704. 10.1155/2013/958704 Uneno Y, Yokoyama A, Nishikawa Y, Funakoshi T, Ozaki Y, Aoyama I, et al. Paraneoplastic Limbic Encephalitis in a Human Epidermal Growth Factor Receptor-2-positive Gastric Cancer Patient Treated with Trastuzumab-combined Chemotherapy: A Case Report and Literature Review. Intern Med. 2016;55(18):2605–9. 10.2169/internalmedicine.55.6917 . Ismail II, Alnaser F, Al-Hashel JY. Seronegative limbic encephalitis manifesting as subacute amnestic syndrome: a case report and review of the literature. J Med Case Rep. 2021;24(1):130. 10.1186/s13256-021-02742-4 . Fukuyama K, Funakoshi Y. Successful management of thymic neuroendocrine tumour with paraneoplastic limbic encephalitis. Interdiscip Cardiovasc Thorac Surg. 2024; 2;38(5):ivae103. doi: 10.1093/icvts/ivae103. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 19 Jan, 2026 Read the published version in The Cerebellum → Version 1 posted Editorial decision: Revision requested 21 Dec, 2025 Reviews received at journal 11 Dec, 2025 Reviewers agreed at journal 10 Dec, 2025 Reviewers invited by journal 09 Dec, 2025 Editor assigned by journal 09 Dec, 2025 Submission checks completed at journal 09 Dec, 2025 First submitted to journal 08 Dec, 2025 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. 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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-8304270","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":558690986,"identity":"4499c523-cf1f-4bb2-bd3c-f92065eabbc7","order_by":0,"name":"Ezgi Aslan","email":"","orcid":"","institution":"Istanbul Medeniyet University","correspondingAuthor":false,"prefix":"","firstName":"Ezgi","middleName":"","lastName":"Aslan","suffix":""},{"id":558690987,"identity":"96ea1fc7-57a0-4fd4-9fbb-39f581d188bf","order_by":1,"name":"Asuman Orhan 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16:17:49","extension":"html","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":38304,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8304270/v1/907982364f3c4dfc34057cc3.html"},{"id":98245719,"identity":"f2d609c0-a5e9-4868-8bad-0a9f704099b8","added_by":"auto","created_at":"2025-12-15 16:18:19","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":112873,"visible":true,"origin":"","legend":"\u003cp\u003eAreas demonstrating diffusion restriction are observed in the right cerebellar hemisphere, middle cerebellar peduncle, and vermis (A, B; white arrows).On FLAIR sequences, hyperintense signals and subtle contrast enhancement are noted in both cerebellar hemispheres and the vermis (C, D; black asterisks). Millimetric diffusion restrictions are present in the subcortical white matter of the right temporal lobe (E, F; white arrows) and in the right centrum semiovale (G; black arrow). FLAIR sequences also demonstrate hyperintense gliotic signals in the bilateral periventricular white matter, corona radiata, and centrum semiovale (H, I; white asterisks).\u003c/p\u003e","description":"","filename":"Figure1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8304270/v1/0943f7aa791f45f8103e9d44.jpeg"},{"id":98245678,"identity":"ce913356-8ac4-4a35-8227-45a75edd0117","added_by":"auto","created_at":"2025-12-15 16:18:17","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":281368,"visible":true,"origin":"","legend":"\u003cp\u003e18F-FDG PET/CT showed a hypermetabolic nodular lesion approximately 25x17 mm in size in the posterior right lobe of the thyroid gland (SUVmax: 8.6) (a, black arrow, and d, e, white arrows), and hypometabolism in the right cerebellar hemisphere (b, c, white arrows).\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8304270/v1/798c84e24a6cb4ed6d9378df.jpg"},{"id":101153375,"identity":"2e0e0caa-8420-44e2-a88c-cac88163c2f0","added_by":"auto","created_at":"2026-01-26 16:15:01","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":719663,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8304270/v1/c8231bdc-20f8-41e8-84f0-ca8371738564.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A Rare Case of Anti-Yo Positive Paraneoplastic Limbic Encephalitis Associated with Thyroid– Parathyroid Adenoma","fulltext":[{"header":"Introduction","content":"\u003cp\u003eImmune-mediated neurological disorders are known as paraneoplastic neurological syndromes (PNS) associated with underlying neoplasms, independent of direct tumor invasion or metastasis [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Although they account for less than 10% of all paraneoplastic syndromes, PNS can cause severe neurological dysfunction. Limbic encephalitis (LE) presents with seizures, memory deficits, and behavioral or personality changes, often due to autoimmune or paraneoplastic mechanisms [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The anti-Yo (PCA-1) antibody is a well-known marker of paraneoplastic cerebellar degeneration, most commonly found in women with breast or ovarian malignancies [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Reports of anti-Yo\u0026ndash;positive LE in males or in association with benign tumors are exceedingly rare [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eTo our knowledge, no prior study has described anti-Yo\u0026ndash;associated limbic encephalitis secondary to a benign thyroid\u0026ndash;parathyroid adenoma. This case aims to broaden the clinical spectrum of anti-Yo\u0026ndash;related disorders and highlight the relevance of antineuronal antibody screening in atypical neurological presentations.\u003c/p\u003e"},{"header":"Case Report","content":"\u003cp\u003eA 59-year-old man was taken in for a 5-month complaint of epileptic seizures, tep-by-step lower limb weakness for two months, and recent onset of dysarthria and confusion. Neurological examination revealed mild somnolence, dysarthric speech, left upper limb distal weakness (\u0026minus;\u0026thinsp;5/5), lower limb weakness (4/5), bilateral flexor plantar responses, and a positive Hoffman sign on the left. Diffusion restriction was seen in the middle cerebellar peduncles and cerebellar hemispheres on cranial MRI. Additionally, FLAIR sequences show hyperintense gliotic signals in the centrum semiovale, corona radiata, and bilateral periventricular white matter (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Analysis of the cerebrospinal fluid (CSF) indicated increased protein 78 mg/dL (15\u0026ndash;45 mg/dL) with negative cytology and pathogen PCR results. Serum testing revealed anti-Yo antibody positivity. MRI of the brain showed multiple diffusion restrictions in the cerebellar hemispheres, vermis, and middle cerebellar peduncles. PET-CT revealed a hypermetabolic lesion (25 \u0026times; 17 mm) in the posterior aspect of the right thyroid lobe. Cystic and solid components compatible with parathyroid adenoma were found during a fine-needle aspiration biopsy. (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Immunohistochemistry revealed thyroid follicular cells positive for TTF-1 and negative for parathormone, confirming benign thyroidal degeneration. Intravenous methylprednisolone treatment consisted of followed by five days of intravenous immunoglobulin (IVIG). After therapy, muscle strength improved, gait ataxia regressed, and speech became intelligible.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAnti-Yo antibodies are directed against Purkinje cell cytoplasmic antigens and are strongly associated with paraneoplastic cerebellar degeneration [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Limbic involvement, however, is rare and has been mainly reported in association with lung, prostate, or gastrointestinal adenocarcinomas [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe present case is remarkable for three reasons: [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] it occurred in a male patient, [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] it was associated with a benign thyroid\u0026ndash;parathyroid adenoma, and [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] cerebellar and limbic involvement coexisted. This expands the recognized clinical and pathological spectrum of anti-Yo\u0026ndash;associated disorders.\u003c/p\u003e\u003cp\u003eWhile anti-Yo\u0026ndash;positive PNS are often refractory to immunotherapy [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], our patient exhibited marked improvement following high-dose corticosteroids and IVIG. This supports the importance of early recognition and aggressive immunomodulatory therapy [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Additionally, this case suggests that benign tumors may also elicit paraneoplastic immune responses. Anti-Yo antibodies are not restricted to cerebellar systems but may also affect the limbic network. Clinicians should therefore consider paraneoplastic and autoimmune etiologies in unexplained encephalitic syndromes [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis is the first documented case of anti-Yo\u0026ndash;positive limbic encephalitis associated with a benign thyroid\u0026ndash;parathyroid adenoma.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eConsent to Publish declaration\u003c/strong\u003e:\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eWritten informed consent forms were obtained from the patients.\u003c/p\u003e\n\u003ch2\u003eFunding\u0026nbsp;Declaration\u003c/strong\u003e:\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eNo funds, grants, or other support were received\u0026mdash;no conflict of interest.\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eConceptualization: AOV; Data curation: EA; Formal analysis: AOV; Funding acquisition: XXX; Investigation: AOV, EA; Methodology: AOV; Project administration: AOV; Resources: AOV; Software: XXX; Supervision: AOV, EA, BB, MTT; Validation: XXX; Visualization: BB, MTT; Writing - original draft: AOV, BB; Writing - review \u0026amp; editing: AOV, EA.\u003c/p\u003e\n\u003ch2\u003eAcknowledgement\u003c/h2\u003e\n\u003cp\u003eAsuman Orhan Varoglu M.D.Istanbul Medeniyet University, Medical FacultyDepartments of Neurology Istanbul, Turkey, Tel: +90 216 5664000 Fax: +90 216 5664023e-mail:[email protected]/08/2025We would like to submit a manuscript authored by Varoglu for consideration to be published in \u0026ldquo;The Cerebellum\u0026rdquo;. Our manuscript is titled \u0026ldquo;A Rare Case of Anti-Yo Positive Paraneoplastic Limbic Encephalitis Associated with Thyroid\u0026ndash;Parathyroid Adenoma\u0026rdquo;. The manuscript has not been published, nor will be simultaneously submitted or published elsewhere. All co-authors have approved the manuscript in its current form for submission to \u0026ldquo; The Cerebellum\u0026rdquo;. Thank you very much for your close attention. We are looking forward to hearing from you.Sincerely yours, Asuman Orhan Varoglu M.D Associate Professor of the Department of Neurology\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGultekin SH, Rosenfeld MR, Voltz R, et al. Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumour association in 50 patients. Brain. 2000;123(7):1481\u0026ndash;94. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/brain/123.7.1481\u003c/span\u003e\u003cspan address=\"10.1093/brain/123.7.1481\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCoker RK, Doran RM, Moss RJ, et al. A case of limbic encephalitis presenting as a paraneoplastic manifestation of limited-stage small cell lung cancer: a case report. J Med Case Rep. 2010;4:408. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/1752-1947-4-408\u003c/span\u003e\u003cspan address=\"10.1186/1752-1947-4-408\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFurneaux HF, Rosenblum MK, Dalmau J, et al. Anti-Hu associated paraneoplastic limbic encephalitis. Dev Med Child Neurol. 2012;54(9):850\u0026ndash;6. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/j.1469-8749.2012.04221.x\u003c/span\u003e\u003cspan address=\"10.1111/j.1469-8749.2012.04221.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGiometto B, Grisold W, Vitaliani R, et al. Paraneoplastic limbic encephalitis: clinical findings and recommended diagnostic work-up. Arch Neurol. 2010;67(3):330\u0026ndash;5. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/archneurol.2009.341\u003c/span\u003e\u003cspan address=\"10.1001/archneurol.2009.341\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDubey D, Pittock SJ, Kelly CR, et al. Autoimmune encephalitis epidemiology and a comparison to infectious encephalitis. Ann Neurol. 2018;83(1):166\u0026ndash;77. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/ana.25131\u003c/span\u003e\u003cspan address=\"10.1002/ana.25131\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGultekin SH, Rosenfeld MR, Voltz R, Eichen J, Posner JB, Dalmau J. Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumour association in 50 patients. Brain. 2000;123(Pt 7):1481\u0026ndash;94. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/brain/123.7.1481\u003c/span\u003e\u003cspan address=\"10.1093/brain/123.7.1481\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKomori T, Tanaka K, Murai H et al. Improvement of paraneoplastic limbic encephalitis after systemic treatment with rituximab in a patient with B-cell chronic lymphocytic leukemia. Case Rep Hematol. 2013; 2013:958704. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1155/2013/958704\u003c/span\u003e\u003cspan address=\"10.1155/2013/958704\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eUneno Y, Yokoyama A, Nishikawa Y, Funakoshi T, Ozaki Y, Aoyama I, et al. Paraneoplastic Limbic Encephalitis in a Human Epidermal Growth Factor Receptor-2-positive Gastric Cancer Patient Treated with Trastuzumab-combined Chemotherapy: A Case Report and Literature Review. Intern Med. 2016;55(18):2605\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2169/internalmedicine.55.6917\u003c/span\u003e\u003cspan address=\"10.2169/internalmedicine.55.6917\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eIsmail II, Alnaser F, Al-Hashel JY. Seronegative limbic encephalitis manifesting as subacute amnestic syndrome: a case report and review of the literature. J Med Case Rep. 2021;24(1):130. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s13256-021-02742-4\u003c/span\u003e\u003cspan address=\"10.1186/s13256-021-02742-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFukuyama K, Funakoshi Y. Successful management of thymic neuroendocrine tumour with paraneoplastic limbic encephalitis. Interdiscip Cardiovasc Thorac Surg. 2024; 2;38(5):ivae103.\u003c/span\u003e \u003cspan\u003edoi: 10.1093/icvts/ivae103.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"the-cerebellum","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cere","sideBox":"Learn more about [The Cerebellum](http://link.springer.com/journal/12311)","snPcode":"12311","submissionUrl":"https://submission.nature.com/new-submission/12311/3","title":"The Cerebellum","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Anti-Yo Antibodies, Paraneoplastic Limbic Encephalitis, Thyroid–Parathyroid Adenoma, Autoimmunity","lastPublishedDoi":"10.21203/rs.3.rs-8304270/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8304270/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e\u003cp\u003eParaneoplastic neurological syndromes (PNS) are typically associated with malignant neoplasms. The anti-Yo antibody is classically linked to paraneoplastic cerebellar degeneration; its coexistence with limbic encephalitis is extremely rare. We report the first case of anti-Yo\u0026ndash;positive limbic encephalitis associated with a benign thyroid\u0026ndash;parathyroid adenoma.\u003c/p\u003e\u003ch2\u003eCase Report:\u003c/h2\u003e\u003cp\u003eA 59-year-old male presented with epileptic seizures, left upper limb weakness, dysarthria, and confusion. Serum anti-Yo antibody was positive. Cranial MRI revealed diffusion restriction in the cerebellar hemispheres and middle cerebellar peduncles. PET-CT showed intense FDG uptake in the posterior right thyroid lobe. A fine-needle aspiration biopsy showed solid and cystic elements consistent with a parathyroid adenoma. The patient received high-dose intravenous methylprednisolone followed by intravenous immunoglobulin, resulting in clinical improvement.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eThis report presents the first documented association between anti-Yo\u0026ndash;positive limbic encephalitis and a benign thyroid\u0026ndash;parathyroid adenoma. It emphasizes the importance of early immunotherapy and multidisciplinary evaluation in rare paraneoplastic syndromes.\u003c/p\u003e","manuscriptTitle":"A Rare Case of Anti-Yo Positive Paraneoplastic Limbic Encephalitis Associated with Thyroid– Parathyroid Adenoma","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-15 16:10:07","doi":"10.21203/rs.3.rs-8304270/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-21T10:33:04+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-11T08:36:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"170537250981673204823340297190313957092","date":"2025-12-10T08:18:28+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-12-09T19:14:30+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-12-09T08:23:08+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-12-09T08:19:40+00:00","index":"","fulltext":""},{"type":"submitted","content":"The Cerebellum","date":"2025-12-08T06:22:52+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"the-cerebellum","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cere","sideBox":"Learn more about [The Cerebellum](http://link.springer.com/journal/12311)","snPcode":"12311","submissionUrl":"https://submission.nature.com/new-submission/12311/3","title":"The Cerebellum","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"7c841e57-43b2-4e82-ae95-5faa88e2883d","owner":[],"postedDate":"December 15th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-01-26T16:13:09+00:00","versionOfRecord":{"articleIdentity":"rs-8304270","link":"https://doi.org/10.1007/s12311-026-01958-8","journal":{"identity":"the-cerebellum","isVorOnly":false,"title":"The Cerebellum"},"publishedOn":"2026-01-19 15:57:29","publishedOnDateReadable":"January 19th, 2026"},"versionCreatedAt":"2025-12-15 16:10:07","video":"","vorDoi":"10.1007/s12311-026-01958-8","vorDoiUrl":"https://doi.org/10.1007/s12311-026-01958-8","workflowStages":[]},"version":"v1","identity":"rs-8304270","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8304270","identity":"rs-8304270","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}