Sydenham Chorea with Elevated Interleukin-12 Levels Responsive to Plasmapheresis and Immunotherapy: Case Report

Sydenham Chorea with Elevated Interleukin-12 Levels Responsive to Plasmapheresis and Immunotherapy: Case Report | 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 Sydenham Chorea with Elevated Interleukin-12 Levels Responsive to Plasmapheresis and Immunotherapy: Case Report Zhimin Xu, Jon Rosenberg, Robert Fekete, Anila Thomas This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7122965/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 Introduction Sydenham chorea (SC) presents with random abnormal involuntary movements that occur after an autoimmune reaction to prior group A beta-hemolytic Streptococcal infection. While most cases resolve spontaneously, there are cases with prolonged duration of symptoms and recurrences. Case report A 22-year-old woman presented with a 2-month history of involuntary, brief, random, and irregular movements of the limbs. She had a history of multiple streptococcal throat infections. At age 2 years old, she had scarlet fever. After ruling out other causes of her chorea, she was diagnosed with Sydenham chorea. She received intravenous immunoglobulin as well as oral prednisone and amantadine with full resolution of her symptoms. Conclusion Interleukin-12 was elevated approximately seven months after hospital discharge which is different from previously published findings of elevation only in acute phase of the disease. Intensive immunosuppressive treatment during the acute phase and adherence to antibiotic treatment could have contributed to the full resolution of her chorea. Neurology Sydenham chorea streptococcal infection rheumatic fever amantadine plasmapheresis Figures Figure 1 Figure 2 Introduction Sydenham chorea (SC) presents with random abnormal involuntary movements that occur after an autoimmune reaction to prior to prior group A beta-hemolytic Streptococcal infection [ 1 ]. The name of the disorder comes from the Greek word for “dance” which is "choreia" (χορεία). SC is one of the disorders that is thought to have been called dance of Saint Vitus. The prevailing theory is that antibodies to the streptococcal infection mistakenly target basal ganglia [ 2 ]. SC is associated with acute rheumatic fever in which a similar mechanism leads to carditis, arthritis, and erythema marginatum. While most cases resolve spontaneously, there are cases with prolonged duration of symptoms and recurrences [ 3 ]. Case Report/Case Presentation A 22-year-old woman presented to the Emergency Department (ED) on December 30th, 2022, with a two-month history of involuntary, brief, random, and irregular movements of the limbs, and slurred speech for one week. She has a history of scarlet fever at age 2. Her symptoms included intermittent movements of the mouth and tongue, writhing movements of the right hand, and her right foot. She also reported speech difficulties. The patient had a recent history of streptococcal throat infection in September 2022, treated with Amoxicillin 500 mg orally twice daily for 10 days. In October, she presented to the ED with fever to 102 F, neck pain, photophobia and a sore throat, and was diagnosed with a viral respiratory infection. The next month she began experiencing difficulty ambulating, performing tasks with her right hand, weight loss, fatigue, redness and warmth in her knuckles, and worsening speech difficulties. Her primary care physician ordered a brain MRI which she was told was negative and her broad constellation of symptoms was attributed to stress. She presented to the ED due to worsening involuntary movements which led to dropping objects that she was holding. Past medical history significant for multiple strep throat infections including scarlet fever at age 2 years old and ADHD treated with Ritalin until age 14. Born in Egypt to American parents, she moved to the US for college in 2018 and currently works as a teacher for autistic children, living with her grandparents and mother. Her family history was significant for Alzheimer's disease in her maternal grandmother and mother, and a paternal half-sister with a history of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS). The physical examination revealed a systolic murmur at the apex. Oropharyngeal exam revealed no exudates. Tonsils were not swollen and neck was supple. Psychiatric assessment indicated increased anxiety and irritability. She had a paranoid belief that nurses would discharge her in the middle of the night. Neurological examination was significant for mildly slurred speech, mouth dyskinesias, tongue darting, and right hand writhing movements that changed throughout the encounter. Video 1 and Video 2 demonstrate these movements. Milkmaid sign was present when attempting hand grip. She also exhibited hand spooning (wrist arching and hyperextension of fingers), elbow flexion when asked to lift arms (touchdown sign), and abnormal gait with the intermittent sideways movement of the right foot. Her hyperkinetic movements were consistent with chorea. Throat culture from the ED revealed Beta-hemolytic streptococcus, non-group A. Prior throat culture results performed at different hospitals were not available. Blood culture was negative. Serum anti-streptolysin O test was negative. Lumbar puncture revealed cerebrospinal fluid (CSF) protein of 20, lactic acid 1.0 mmol/L, glucose 58, and no oligoclonal bands. CSF red blood cell count was 1 / cubic mm. CSF white blood cell count was 113 / cubic mm with 82% lymphocytes, 12 percent monocytes, and 6 percent polynucleated cells. CSF culture was negative. Mayo Clinic Laboratory (Rochester, MN, USA) paraneoplastic antibody panel was negative for Amphiphysin, AGNA-1, ANNA-1, ANNA-2, ANNA-3, CASPR-2, CRMP-5, DPPX, GAD65, GRAF1, IgLON5, ITPR1, KLHL11, LGI1, mGluR1, NIF, NMDA-R, P/Q-Type Calcium Channel, PCA-1, PCA-2, PCA-Tr antibodies in the cerebrospinal fluid (CSF) and serum. The serum was also negative for P/Q-Type Calcium Channel antibody. Oligoclonal bands were negative. C-reactive protein in the ED was low at < 0.10 mg/dL. Serum ceruloplasmin was low at 15 mg/dL. 12-hour urine copper was negative. MRI brain performed in the hospital revealed normal to mildly hyperintense caudate nuclei which appeared mildly swollen (Fig. 1 ). She received five plasmapheresis treatments in the hospital after which she was discharged. Her chorea was treated with amantadine 100 mg orally daily for three weeks. Prednisone 60mg orally (1mg/kg) was used for one week with 10 mg taper every two weeks. Patient presented for outpatient follow-up in July of 2023. Her chorea was completely resolved. She was compliant with chronic oral penicillin VK 250 mg twice daily prescription. Interleukin-12 at this time was elevated to 3.9 pg/mL (normal < = 1.9 pg/mL). Her trans thoracic echocardiogram showed moderate eccentric mitral regurgitation and small vegetation versus mild thickening of both mitral leaflets at the tips, possibly part of subvalvular apparatus (Fig. 2 ). Patient did not wish to undertake trans esophageal echocardiogram for further evaluation for small valvular vegetation. Discussion Diagnosing SC is mostly clinical with presence of characteristic neurological and behavioral symptoms following streptococcal infection. Supporting evidence includes elevated antistreptolysin O titers and other streptococcal antibodies, although their absence does not preclude the diagnosis [ 4 ]. Neuroimaging is typically normal but is valuable for excluding other conditions. The Jones criteria are relevant for a comprehensive diagnosis with other acute rheumatic fever manifestations. Differential diagnosis including hereditary chorea, structural or vascular brain abnormalities, other autoimmune disorders, infections, metabolic, and toxin exposure. Particularly notable is Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS), which shares the autoimmune response to streptococcal infection with SC but typically presents with abrupt onset OCD or tic disorders. Careful distinction between SC and PANDAS is crucial for appropriate management [ 5 ]. The treatment of SC focuses on symptom management and recurrence prevention. Dopamine receptor antagonists (e.g., haloperidol) and antiepileptics (e.g., valproic acid) are commonly used for chorea. In this case, amantadine was helpful. Severe or refractory cases may benefit from immunomodulatory therapies, such as corticosteroids, intravenous immunoglobulin (IVIG), or plasmapheresis. Our patient received corticosteroid as well as plasmapheresis given significant chorea which led to difficulty grasping objects normally. Long term antibiotic prophylaxis, primarily with penicillin, is important for preventing recurrent streptococcal infections and subsequent clinical episodes [ 6 ]. 24-hour urine copper was low which argues against Wilson’s disease. MRI brain did not show any correlates of Wilson’s disease such as panda sign. High sensitivity CRP (hsCRP) at discharge was elevated to 3.6 mg/L and returned to normal at 0.4 mg/L about 2.5 months after discharge which is consistent with resolution of symptoms. Church et al. report that interleukin-12 (IL-12) was elevated in acute but not persistent SC [ 7 ]. In this patient, this cytokine was elevated seven months after the initial ED presentation and also at a time when the chorea has resolved. IL-12 has a complex proinflammatory as well as immunoregulatory function [ 8 ], but given that acute phase reactants and symptoms have normalized at follow-up, it would be functioning in a regulatory capacity. This strength of this report is that provides a detailed look at a case of SC treated with immunotherapy and plasmapheresis leading to complete resolution of symptoms, with unusual elevation of IL-12 despite resolution of symptoms. The limitation of the report is that data from one patient is not generalizable and further research is needed to understand the role of interleukins in acute and persistent SC. Declarations Statement of Ethics Please address the following aspects in your Statement of Ethics. Study approval statement : According the New York Medical College Office of Research Administration (NYMC ORA), “Case reports submitted for publication do not strictly meet the criteria of research. The institution’s policy, therefore, is that a case report is not research that must be approved by the IRB.” Consent to publish statement : Written informed consent was obtained from the patient for publication of the details of her medical case and any accompanying images. Conflict of Interest Statement The authors have no conflicts of interest to declare. Funding Sources This study was not supported by any sponsor or funder. Author Contributions ZX conception of the work, manuscript initial draft, obtaining video, editing video, editing manuscript, literature review JR conception of the work, manuscript initial draft, interpretation of clinical data, editing video, editing manuscript RF interpretation of clinical data, editing video, editing manuscript, literature review AT interpretation of clinical data, obtaining video, editing manuscript All authors approve the final version of the manuscript. Data Availability Statement All relevant data is included in the manuscript. References Stollerman GH. Rheumatic fever. Lancet. 1997;349(9056):935 942. doi:10.1016/S0140 106 6736(96)06364 7 107 Cunningham MW, Cox CJ. Autoimmunity against dopamine receptors in neuropsychiatric and 108 movement disorders: a review of Sydenham chorea and beyond. Acta Physiol (Oxf). 109 2016;216(1):90 100. doi:10.1111/apha.12614 Solela G, Fedlu M. Rare Recurrence of Sydenham Chorea in an Adult: A Case Report. Int Med Case Rep J. 2023 May 9;16:265-268. doi: 10.2147/IMCRJ.S405371. PMID: 37193054; PMCID: PMC10182765. Loiselle CR, Singer HS. Genetics of childhood disorders: XXXI. Autoimmune disorders, part 4: 111 is Sydenham chorea an autoimmune disorder?. J Am Acad Child Adolesc Psychiatry. 112 2001;40(10):1234-1236. doi:10.1097/00004583-200110000-00019 Vreeland A, Thienemann M, Cunningham M, Muscal E, Pittenger C, Frankovich J. 114 Neuroinflammation in Obsessive Compulsive Disorder: Sydenham Chorea, Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections, and Pediatric 116 Acute Onset Neuropsychiatric Syndrome. Psychiatr Clin North Am. 2023;46(1):69--88. 117 doi:10.1016/j.psc.2022.11.004 Tariq S, Niaz F, Waseem S, et al. Managing and treating Sydenham chorea: A systematic review. Brain Behav. 2023;13(6):e3035. doi:10.1002/brb3.3035 Church AJ, Dale RC, Cardoso F, et al. CSF and serum immune parameters in Sydenham's chorea: evidence of an autoimmune syndrome? J Neuroimmunol. 2003 Mar;136(1-2):149-53. doi: 10.1016/s0165-5728(03)00012-2. PMID: 12620654 DOI: 10.1016/s0165-5728(03)00012-2 Trinchieri G. Proinflammatory and immunoregulatory functions of interleukin-12. Int Rev Immunol. 1998;16(3-4):365-96. doi: 10.3109/08830189809043002. PMID: 9505196. New York Medical College Office of Research Administration. Policies and Procedures for the Conduct of Research Involving Human Subjects [Cited 2025 July 14]. https://www.nymc.edu/media/schools-and-colleges/nymc/pdf/human-subjects-research/IRBmanual.pdf Additional Declarations The authors declare no competing interests. Supplementary Files SydenhamRosenbergVideo.mov Video 1. Bilateral upper extremity, trunk, and lower extremity chorea, with choreic gait. WNL2024102186RosenbergVideo2.mov Video 2. Bilateral upper extremity, head, face, and tongue chorea with motor impersistence. 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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-7122965","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":485282044,"identity":"91d12883-a508-4f06-be75-c4330bc071d2","order_by":0,"name":"Zhimin Xu","email":"","orcid":"","institution":"New York Medical College","correspondingAuthor":false,"prefix":"","firstName":"Zhimin","middleName":"","lastName":"Xu","suffix":""},{"id":485282110,"identity":"7ad6befd-e341-4aa9-ad27-db457fc9c8c0","order_by":1,"name":"Jon Rosenberg","email":"","orcid":"","institution":"New York Medical College","correspondingAuthor":false,"prefix":"","firstName":"Jon","middleName":"","lastName":"Rosenberg","suffix":""},{"id":485282111,"identity":"e0807e7e-58dc-424f-8b77-b310355888a0","order_by":2,"name":"Robert Fekete","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9klEQVRIiWNgGAWjYFACHhAhxyABoj42gEjGxgOEtSQYA7UwMzDObABpZWwgXgszbwPENrxazNt7Dz6u/GEgJ9nef/Cx7Q6bOt32w0BbamyicWmROXMu2fBMgoGxNM9hZuPcM2kSZmcSgVqOpeU24NAiIZFjJtmQ8CdxnkQym3Ru22EJswNALYwNh/FpMf/ZkGBQP0/+MftvS5CW8w8JajFjBGpJkJZgZmNmBGm5QcgWnnPJkg1pBoYze5KNJXvb0iS33QDakoDPL+y9Bz822BjISxw/+PDDzzYbfrPz6Q8ffKixwakFB0ggTfkoGAWjYBSMAjQAAO/dXF4eaCYtAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-0627-8340","institution":"New York Medical College","correspondingAuthor":true,"prefix":"","firstName":"Robert","middleName":"","lastName":"Fekete","suffix":""},{"id":485282112,"identity":"cdf4776a-0544-43fb-815b-5ad1f2d5cb57","order_by":3,"name":"Anila Thomas","email":"","orcid":"","institution":"New York Medical College","correspondingAuthor":false,"prefix":"","firstName":"Anila","middleName":"","lastName":"Thomas","suffix":""}],"badges":[],"createdAt":"2025-07-14 15:53:58","currentVersionCode":1,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":true,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-7122965/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7122965/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":86773730,"identity":"48bce13b-66fd-4713-b40f-7f72497f0f5d","added_by":"auto","created_at":"2025-07-15 12:18:50","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":894911,"visible":true,"origin":"","legend":"\u003cp\u003eMRI Fluid Attenuation Inversion Recovery (FLAIR) image demonstrating enlarged caudate nuclei bilaterally and mildly hyperintense bilateral putamina\u003c/p\u003e","description":"","filename":"Figure1FLAIRenlargedcaudatemildyhyperintenseputamen.png","url":"https://assets-eu.researchsquare.com/files/rs-7122965/v1/deb0de74c86fd712d41627b2.png"},{"id":86773736,"identity":"c412d264-f83a-4ddf-ba31-56af5fbeb6f2","added_by":"auto","created_at":"2025-07-15 12:18:51","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":449473,"visible":true,"origin":"","legend":"\u003cp\u003eEchocardiogram image showing questionable early vegetation (outlined in green) versus mild thickening of mitral valve leaflets\u003c/p\u003e","description":"","filename":"Figure2echocardiogramvegetation.png","url":"https://assets-eu.researchsquare.com/files/rs-7122965/v1/87ec34aece5c12e31437522e.png"},{"id":86774927,"identity":"a0293048-cc81-44b2-9c54-17c9c36ef67d","added_by":"auto","created_at":"2025-07-15 12:26:55","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1595807,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7122965/v1/ccac73a9-2970-4ed0-9e1d-65c1e4d79e11.pdf"},{"id":86773734,"identity":"2d937e2b-057b-40a9-b262-7229174b96b8","added_by":"auto","created_at":"2025-07-15 12:18:50","extension":"mov","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":10218927,"visible":true,"origin":"","legend":"\u003cp\u003eVideo 1. Bilateral upper extremity, trunk, and lower extremity chorea, with choreic gait.\u003c/p\u003e","description":"","filename":"SydenhamRosenbergVideo.mov","url":"https://assets-eu.researchsquare.com/files/rs-7122965/v1/b249125ccef6c3b360a8f9b0.mov"},{"id":86773737,"identity":"48bc6e78-b1b7-448e-83af-81bbd4cf1e7e","added_by":"auto","created_at":"2025-07-15 12:18:51","extension":"mov","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":18149463,"visible":true,"origin":"","legend":"\u003cp\u003eVideo 2. Bilateral upper extremity, head, face, and tongue chorea with motor impersistence.\u003c/p\u003e","description":"","filename":"WNL2024102186RosenbergVideo2.mov","url":"https://assets-eu.researchsquare.com/files/rs-7122965/v1/dfeb125a3de15bc7b431c2fc.mov"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eSydenham Chorea with Elevated Interleukin-12 Levels Responsive to Plasmapheresis and Immunotherapy: Case Report\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSydenham chorea (SC) presents with random abnormal involuntary movements that occur after an autoimmune reaction to prior to prior group A beta-hemolytic Streptococcal infection [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The name of the disorder comes from the Greek word for “dance” which is \"choreia\" (χορεία). SC is one of the disorders that is thought to have been called dance of Saint Vitus. The prevailing theory is that antibodies to the streptococcal infection mistakenly target basal ganglia [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. SC is associated with acute rheumatic fever in which a similar mechanism leads to carditis, arthritis, and erythema marginatum. While most cases resolve spontaneously, there are cases with prolonged duration of symptoms and recurrences [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e"},{"header":"Case Report/Case Presentation","content":"\u003cp\u003eA 22-year-old woman presented to the Emergency Department (ED) on December 30th, 2022, with a two-month history of involuntary, brief, random, and irregular movements of the limbs, and slurred speech for one week. She has a history of scarlet fever at age 2. Her symptoms included intermittent movements of the mouth and tongue, writhing movements of the right hand, and her right foot. She also reported speech difficulties. The patient had a recent history of streptococcal throat infection in September 2022, treated with Amoxicillin 500 mg orally twice daily for 10 days. In October, she presented to the ED with fever to 102 F, neck pain, photophobia and a sore throat, and was diagnosed with a viral respiratory infection. The next month she began experiencing difficulty ambulating, performing tasks with her right hand, weight loss, fatigue, redness and warmth in her knuckles, and worsening speech difficulties. Her primary care physician ordered a brain MRI which she was told was negative and her broad constellation of symptoms was attributed to stress. She presented to the ED due to worsening involuntary movements which led to dropping objects that she was holding.\u003c/p\u003e\u003cp\u003ePast medical history significant for multiple strep throat infections including scarlet fever at age 2 years old and ADHD treated with Ritalin until age 14. Born in Egypt to American parents, she moved to the US for college in 2018 and currently works as a teacher for autistic children, living with her grandparents and mother. Her family history was significant for Alzheimer's disease in her maternal grandmother and mother, and a paternal half-sister with a history of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS).\u003c/p\u003e\u003cp\u003eThe physical examination revealed a systolic murmur at the apex. Oropharyngeal exam revealed no exudates. Tonsils were not swollen and neck was supple. Psychiatric assessment indicated increased anxiety and irritability. She had a paranoid belief that nurses would discharge her in the middle of the night. Neurological examination was significant for mildly slurred speech, mouth dyskinesias, tongue darting, and right hand writhing movements that changed throughout the encounter. Video 1 and Video 2 demonstrate these movements. Milkmaid sign was present when attempting hand grip. She also exhibited hand spooning (wrist arching and hyperextension of fingers), elbow flexion when asked to lift arms (touchdown sign), and abnormal gait with the intermittent sideways movement of the right foot. Her hyperkinetic movements were consistent with chorea.\u003c/p\u003e\u003cp\u003eThroat culture from the ED revealed Beta-hemolytic streptococcus, non-group A. Prior throat culture results performed at different hospitals were not available. Blood culture was negative. Serum anti-streptolysin O test was negative.\u003c/p\u003e\u003cp\u003eLumbar puncture revealed cerebrospinal fluid (CSF) protein of 20, lactic acid 1.0 mmol/L, glucose 58, and no oligoclonal bands. CSF red blood cell count was 1 / cubic mm. CSF white blood cell count was 113 / cubic mm with 82% lymphocytes, 12 percent monocytes, and 6 percent polynucleated cells. CSF culture was negative.\u003c/p\u003e\u003cp\u003eMayo Clinic Laboratory (Rochester, MN, USA) paraneoplastic antibody panel was negative for Amphiphysin, AGNA-1, ANNA-1, ANNA-2, ANNA-3, CASPR-2, CRMP-5, DPPX, GAD65, GRAF1, IgLON5, ITPR1, KLHL11, LGI1, mGluR1, NIF, NMDA-R, P/Q-Type Calcium Channel, PCA-1, PCA-2, PCA-Tr antibodies in the cerebrospinal fluid (CSF) and serum. The serum was also negative for P/Q-Type Calcium Channel antibody. Oligoclonal bands were negative.\u003c/p\u003e\u003cp\u003eC-reactive protein in the ED was low at \u0026lt; 0.10 mg/dL. Serum ceruloplasmin was low at 15 mg/dL. 12-hour urine copper was negative. MRI brain performed in the hospital revealed normal to mildly hyperintense caudate nuclei which appeared mildly swollen (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). She received five plasmapheresis treatments in the hospital after which she was discharged. Her chorea was treated with amantadine 100 mg orally daily for three weeks. Prednisone 60mg orally (1mg/kg) was used for one week with 10 mg taper every two weeks.\u003c/p\u003e\u003cp\u003ePatient presented for outpatient follow-up in July of 2023. Her chorea was completely resolved. She was compliant with chronic oral penicillin VK 250 mg twice daily prescription. Interleukin-12 at this time was elevated to 3.9 pg/mL (normal \u0026lt; = 1.9 pg/mL). Her trans thoracic echocardiogram showed moderate eccentric mitral regurgitation and small vegetation versus mild thickening of both mitral leaflets at the tips, possibly part of subvalvular apparatus (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Patient did not wish to undertake trans esophageal echocardiogram for further evaluation for small valvular vegetation.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eDiagnosing SC is mostly clinical with presence of characteristic neurological and behavioral symptoms following streptococcal infection. Supporting evidence includes elevated antistreptolysin O titers and other streptococcal antibodies, although their absence does not preclude the diagnosis [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Neuroimaging is typically normal but is valuable for excluding other conditions. The Jones criteria are relevant for a comprehensive diagnosis with other acute rheumatic fever manifestations.\u003c/p\u003e\u003cp\u003eDifferential diagnosis including hereditary chorea, structural or vascular brain abnormalities, other autoimmune disorders, infections, metabolic, and toxin exposure. Particularly notable is Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS), which shares the autoimmune response to streptococcal infection with SC but typically presents with abrupt onset OCD or tic disorders. Careful distinction between SC and PANDAS is crucial for appropriate management [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe treatment of SC focuses on symptom management and recurrence prevention. Dopamine receptor antagonists (e.g., haloperidol) and antiepileptics (e.g., valproic acid) are commonly used for chorea. In this case, amantadine was helpful. Severe or refractory cases may benefit from immunomodulatory therapies, such as corticosteroids, intravenous immunoglobulin (IVIG), or plasmapheresis. Our patient received corticosteroid as well as plasmapheresis given significant chorea which led to difficulty grasping objects normally. Long term antibiotic prophylaxis, primarily with penicillin, is important for preventing recurrent streptococcal infections and subsequent clinical episodes [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e24-hour urine copper was low which argues against Wilson\u0026rsquo;s disease. MRI brain did not show any correlates of Wilson\u0026rsquo;s disease such as panda sign. High sensitivity CRP (hsCRP) at discharge was elevated to 3.6 mg/L and returned to normal at 0.4 mg/L about 2.5 months after discharge which is consistent with resolution of symptoms.\u003c/p\u003e\u003cp\u003eChurch et al. report that interleukin-12 (IL-12) was elevated in acute but not persistent SC [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In this patient, this cytokine was elevated seven months after the initial ED presentation and also at a time when the chorea has resolved. IL-12 has a complex proinflammatory as well as immunoregulatory function [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], but given that acute phase reactants and symptoms have normalized at follow-up, it would be functioning in a regulatory capacity.\u003c/p\u003e\u003cp\u003eThis strength of this report is that provides a detailed look at a case of SC treated with immunotherapy and plasmapheresis leading to complete resolution of symptoms, with unusual elevation of IL-12 despite resolution of symptoms. The limitation of the report is that data from one patient is not generalizable and further research is needed to understand the role of interleukins in acute and persistent SC.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch6\u003eStatement of Ethics\u003c/h6\u003e\n\u003cp\u003ePlease address the following aspects in your Statement of Ethics. \u003c/p\u003e\n\u003cp\u003e\u003cu\u003eStudy approval statement\u003c/u\u003e: \u003c/p\u003e\n\u003cp\u003eAccording the New York Medical College Office of Research Administration (NYMC ORA), “Case reports submitted for publication do not strictly meet the criteria of research. The institution’s policy, therefore, is that a case report is not research that must be approved by the IRB.”\u003c/p\u003e\n\u003ch6\u003e\u003cu\u003eConsent to publish statement\u003c/u\u003e: \u003c/h6\u003e\n\u003ch6\u003eWritten informed consent was obtained from the patient for publication of the details of her medical case and any accompanying images.\u003c/h6\u003e\n\u003cp\u003eConflict of Interest Statement\u003c/p\u003e\n\u003cp\u003eThe authors have no conflicts of interest to declare.\u003c/p\u003e\n\u003cp\u003eFunding Sources\u003c/p\u003e\n\u003cp\u003eThis study was not supported by any sponsor or funder.\u003c/p\u003e\n\u003cp\u003eAuthor Contributions\u003c/p\u003e\n\u003cp\u003eZX conception of the work, manuscript initial draft, obtaining video, editing video, editing manuscript, literature review\u003c/p\u003e\n\u003cp\u003eJR conception of the work, manuscript initial draft, interpretation of clinical data, editing video, editing manuscript\u003c/p\u003e\n\u003cp\u003eRF interpretation of clinical data, editing video, editing manuscript, literature review\u003c/p\u003e\n\u003cp\u003eAT interpretation of clinical data, obtaining video, editing manuscript\u003c/p\u003e\n\u003cp\u003eAll authors approve the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll relevant data is included in the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eStollerman GH. Rheumatic fever. Lancet. 1997;349(9056):935 942. doi:10.1016/S0140 106 6736(96)06364 7 107 \u003c/li\u003e\n\u003cli\u003eCunningham MW, Cox CJ. Autoimmunity against dopamine receptors in neuropsychiatric and 108 movement disorders: a review of Sydenham chorea and beyond. Acta Physiol (Oxf). 109 2016;216(1):90 100. doi:10.1111/apha.12614\u003c/li\u003e\n\u003cli\u003eSolela G, Fedlu M. Rare Recurrence of Sydenham Chorea in an Adult: A Case Report. Int Med Case Rep J. 2023 May 9;16:265-268. doi: 10.2147/IMCRJ.S405371. PMID: 37193054; PMCID: PMC10182765.\u003c/li\u003e\n\u003cli\u003eLoiselle CR, Singer HS. Genetics of childhood disorders: XXXI. Autoimmune disorders, part 4: 111 is Sydenham chorea an autoimmune disorder?. J Am Acad Child Adolesc Psychiatry. 112 2001;40(10):1234-1236. doi:10.1097/00004583-200110000-00019 \u003c/li\u003e\n\u003cli\u003eVreeland A, Thienemann M, Cunningham M, Muscal E, Pittenger C, Frankovich J. 114 Neuroinflammation in Obsessive Compulsive Disorder: Sydenham Chorea, Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections, and Pediatric 116 Acute Onset Neuropsychiatric Syndrome. Psychiatr Clin North Am. 2023;46(1):69--88. 117 doi:10.1016/j.psc.2022.11.004\u003c/li\u003e\n\u003cli\u003eTariq S, Niaz F, Waseem S, et al. Managing and treating Sydenham chorea: A systematic review. Brain Behav. 2023;13(6):e3035. doi:10.1002/brb3.3035\u003c/li\u003e\n\u003cli\u003eChurch AJ, Dale RC, Cardoso F, et al. CSF and serum immune parameters in Sydenham\u0026apos;s chorea: evidence of an autoimmune syndrome? J Neuroimmunol. 2003 Mar;136(1-2):149-53. doi: 10.1016/s0165-5728(03)00012-2. PMID: 12620654 DOI: 10.1016/s0165-5728(03)00012-2\u003c/li\u003e\n\u003cli\u003eTrinchieri G. Proinflammatory and immunoregulatory functions of interleukin-12. Int Rev Immunol. 1998;16(3-4):365-96. doi: 10.3109/08830189809043002. PMID: 9505196.\u003c/li\u003e\n\u003cli\u003eNew York Medical College Office of Research Administration. Policies and Procedures for the Conduct of Research Involving Human Subjects [Cited 2025 July 14]. https://www.nymc.edu/media/schools-and-colleges/nymc/pdf/human-subjects-research/IRBmanual.pdf\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"New York Medical College","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":"Sydenham chorea, streptococcal infection, rheumatic fever, amantadine, plasmapheresis","lastPublishedDoi":"10.21203/rs.3.rs-7122965/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7122965/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eIntroduction\u003c/p\u003e\n\u003cp\u003eSydenham chorea (SC) presents with random abnormal involuntary movements that occur after an autoimmune reaction to prior group A beta-hemolytic Streptococcal infection. While most cases resolve spontaneously, there are cases with prolonged duration of symptoms and recurrences.\u003c/p\u003e\n\u003cp\u003eCase report\u003c/p\u003e\n\u003cp\u003eA 22-year-old woman presented with a 2-month history of involuntary, brief, random, and irregular movements of the limbs. She had a history of multiple streptococcal throat infections. At age 2 years old, she had scarlet fever. After ruling out other causes of her chorea, she was diagnosed with Sydenham chorea. She received intravenous immunoglobulin as well as oral prednisone and amantadine with full resolution of her symptoms.\u003c/p\u003e\n\u003cp\u003eConclusion\u003c/p\u003e\n\u003cp\u003eInterleukin-12 was elevated approximately seven months after hospital discharge which is different from previously published findings of elevation only in acute phase of the disease. Intensive immunosuppressive treatment during the acute phase and adherence to antibiotic treatment could have contributed to the full resolution of her chorea.\u003c/p\u003e","manuscriptTitle":"Sydenham Chorea with Elevated Interleukin-12 Levels Responsive to Plasmapheresis and Immunotherapy: Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-15 12:18:46","doi":"10.21203/rs.3.rs-7122965/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":"73756a78-b3e4-4fac-b1e5-f4625bc80cdf","owner":[],"postedDate":"July 15th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":51516920,"name":"Neurology"}],"tags":[],"updatedAt":"2025-07-15T12:18:46+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-15 12:18:46","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7122965","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7122965","identity":"rs-7122965","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}