Exploring a possible shared pathophysiology in co-occurrence of multiple sclerosis and Hodgkin lymphoma: a case report and review of literature

Exploring a possible shared pathophysiology in co-occurrence of multiple sclerosis and Hodgkin lymphoma: a case report and review of literature | 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 Exploring a possible shared pathophysiology in co-occurrence of multiple sclerosis and Hodgkin lymphoma: a case report and review of literature Ipshita Garg, Yugant Khand, Paunel Agyei, Nestor Galvez-Jimenez, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7161237/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 13 Apr, 2026 Read the published version in BMC Neurology → Version 1 posted 10 You are reading this latest preprint version Abstract INTRODUCTION Multiple sclerosis (MS) and Hodgkin lymphoma (HL) share common epidemiology, genetics and immunological factors. We report a case of a woman who presented with neurological deficits along with systemic symptoms fulfilling criteria for MS with synchronous HL. CASE PRESENTATION A 37-year-old woman presented with bilateral leg weakness, numbness and urinary retention which was preceded by three weeks of night sweats, 25-pound weight loss and anorexia. Neurological examination showed spastic paraparesis, sensory deficit and a left extensor plantar response. A magnetic resonance imaging (MRI) of brain showed multiple non-enhancing white-matter lesions, with patchy areas of peripheral gadolinium (Gd)-enhancement in the thoracic cord. Serology was positive for JC and EBV IgG antibodies. Body imaging revealed a mediastinal mass, and biopsy confirmed classical HL. The patient was given steroid infusions which resulted in mild improvements of leg weakness and numbness. She was started on doxorubicin, bleomycin, dacarbazine and vinblastine (ABVD) for HL. A Gd-enhanced MRI brain obtained after 4 cycles of ABVD showed resolution of enhancing lesions but new T2-FLAIR lesion consistent with active MS. Due to ongoing HL surveillance and concerns regarding immunosuppression, she was not started on disease-modifying therapy for MS. On her annual follow-up, she reported persistent fatigue, transient memory deficit and residual leg numbness. DISCUSSION The relationship between HL and MS has been explored in various studies, revealing an overlap in genetic susceptibility, shared biological pathways through lymphocyte-mediated immunity, JUN kinase activity, and tyrosine phosphorylation, and common environmental factors, such as the presence of EBV. Our patient presented with an atypical thoracic MRI finding of peripheral enhancement which led to further investigation and diagnosis of HL. The concurrent occurrence of MS and HL may point toward shared immune dysregulation. CONCLUSION We report a case of co-occurrence of MS with HL and note neurological stability after treatment with ABVD chemotherapy for HL. The shared genetics and immunological interplay may explain overlaps, but MS and HL still remain distinct pathologies. Multiple sclerosis Hodgkin lymphoma neuro-oncology neuro-immunology case report Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Multiple sclerosis (MS) is a chronic autoimmune demyelinating disorder of the central nervous system, while Hodgkin lymphoma (HL) is a monoclonal lymphoid neoplasm, commonly arising in the cervical lymph nodes. MS and HL share certain common genetics, epidemiology traits, and immunological factors. Both affect immune activation, cell proliferation and lymphocyte-mediated immunity. ( 1 ) The two seemingly distinct diseases have similarities in age distribution, geographical patterns and potential risk factors. However, co-occurrence of these two distinct clinical conditions is rare. While the exact mechanism behind this is poorly understood, shared factors such as genetic susceptibility, Epstein Barr virus (EBV), and variable presentations indicating a relationship between their treatments and relapses may provide insight into potential new diagnostic and therapeutic strategies. ( 2 – 4 ) We report a case of a woman who presented with neurological deficits along with systemic symptoms fulfilling criteria for MS with synchronous HL. This case explores a potential overlap due to shared immunopathogenesis between the occurrence of MS and HL. Case Presentation A 37-year-old previously healthy woman presented to the neurology clinic with a one-week history of progressive bilateral lower limb weakness, numbness, and new-onset urinary retention. She also complained of night sweats, 25-pound unintentional weight loss, and loss of appetite which preceded her neurological symptoms by three weeks. She reported persistent tingling and numbness in both legs which ascended from her feet to her thighs. She also reported an inability to sense bladder fullness leading to episodes of incomplete voiding. She denied fever, recent infections, or prior neurologic symptoms. Her medical history was unremarkable for prior autoimmune or neoplastic diagnoses. She did not smoke or use illicit substances. She had no family history for neurological or oncologic disease. On examination, she was alert and oriented with normal higher cortical functions. Cranial nerves were intact. Motor examination revealed symmetric leg weakness with Medical Research Council score of 4/5. There was an increased tone, spasticity and hyperreflexia with sustained clonus. A left-sided extensor plantar response was noted. Sensory testing showed reduced vibration and proprioception in her feet with preserved pinprick and temperature sensation. She had a spastic and broad-based gait. Bladder ultrasound confirmed urinary retention with elevated post-void residual volumes. She had normal upper extremity coordination. Magnetic resonance imaging (MRI) of the brain with gadolinium (Gd) contrast showed multiple non-enhancing hyperintense lesions in the periventricular and juxtacortical white matter. Figure 1 MRI of the thoracic spine revealed patchy peripheral gadolinium-enhancing lesions within the spinal cord. Figure 2 Cerebrospinal fluid (CSF) analysis had increased immunoglobulin G (IgG) and oligoclonal bands. She had positive IgG antibodies to JC virus and Epstein-Barr virus (EBV) with negative IgM. The serology testing suggested past exposure without any acute infection. A further workup was planned for alternative or co-existing etiologies due to her unusual peripheral enhancement of the thoracic cord and systemic symptoms. Three-months later, a follow-up MRI brain showed worsening contrast-enhanced lesions. Figure 3 A repeat CSF study revealed normal OCBs and IgG index and CSF was negative for malignant cells, JCV DNA, and EBV DNA. A computed tomography (CT) scan of the chest, abdomen and pelvis showed a large anterior mediastinal mass with extensive mediastinal lymphadenopathy. A lymph node biopsy was performed which confirmed the diagnosis of classic Hodgkin lymphoma (HL). A stereotactic brain biopsy of the enhancing lesion was performed to assess the possibility of central nervous system involvement by lymphoma. The biopsy findings showed gliosis and perivascular lymphocytic infiltrates without evidence of malignant cells. The patient was diagnosed with relapsing-remitting multiple sclerosis (RRMS) and classic HL. She initially received intravenous methylprednisolone for five days which showed mild improvement in lower limb strength and sensory symptoms. She was initiated on standard ABVD chemotherapy (doxorubicin, bleomycin, vinblastine, and dacarbazine) given her diagnosis of HL. A follow-up brain MRI showed resolution of previous Gd-enhancing lesions but revealed a new enhancing focus in the left frontal lobe even after completing four cycles of chemotherapy which was consistent with her ongoing demyelinating activity. Figure 4 Her clinical condition remained stable despite the new lesion. She completed a full course of six ABVD cycles. On her follow-up, a positron emission tomography (PET) scan showed residual bulky disease in the chest. She was treated with proton beam radiation therapy to the mediastinum for three months after completion of chemotherapy. During her one-year follow-up, brain MRI showed no new contrast-enhancing lesions but revealed five new supratentorial T2-FLAIR hyperintense lesions which suggested subclinical disease activity. The patient complained of ongoing fatigue, transient short-term memory difficulties, and mild residual numbness in her feet. She remained ambulatory and independent in activities of daily living. Due to ongoing HL surveillance and concerns regarding immunosuppression, she was not started on disease-modifying therapy for MS. She remains under multidisciplinary care by hematology-oncology, neuro-oncology and rehabilitation teams. Discussion The overall risk of cancer in multiple sclerosis (MS) patients is lower, but Hodgkin’s lymphoma (HL) is an exception, though statistical significance was lacking. ( 1 , 2 ) The co-occurrence was initially observed by Newell in 1970, where he noted an epidemiological relation to MS and HL. ( 3 ) Some studies have strong evidence linking Epstein-Barr Virus (EBV) to MS and lymphoproliferative cancer, including HL and certain non-Hodgkin’s lymphoma (NHL), reinforcing its role as a causative organism with delayed complications. While the acceleration of MS occurs as a late complication of EBV infection, lymphoma risk peaks within 2 years after primary EBV exposure. ( 4 ) The shared epidemiological traits between MS and HL, particularly young adult-onset Hodgkin lymphoma (YAHL) is hypothesized with childhood exposure to EBV. The Swedish National cohort study by Montgomery et al. found a statistically significant association between MS and risk of YAHL. ( 1 ) This association was 3.3 times higher in females, possibly due to higher MS prevalence in that subset of population. ( 1 ) This underscores EBV’s pathogenic role highlighting immune dysregulation as a potential bridge between MS and HL. These suggest that EBV might play a role in development of both HL and MS, as a smoldering autoimmune process. A positive EBV serology was present in our patient and could indicate a common immunological precursor to the diagnosis of HL and MS in this case. However, studies fail to account for ethnicity or cannot pinpoint a particular infectious exposure during childhood which could have the development of YAHL. Another study hypothesized that HL and MS share similar geographic distributions. A cross-sectional analysis from 21 countries concluded that HL and MS were common in European countries and showed the inter-age correlation for HL started at age 5 or less while MS only started at age 15 years. ( 5 ) This supports the contention that environmental factors influence the occurrence of HL earlier than MS. There are established studies indicating exposure to sunlight and low serum levels of vitamin D in the occurrence of MS. The role of vitamin D in HL remains unexplored. A Danish population-based cancer registry also concluded that environmental factors are a probable explanation to the familial clustering of MS and HL which also correlates to Newell’s hypothesis. ( 6 ) The co-occurrence of HL and MS cannot be explained with environmental factors alone. The relationship between HL and MS has been explored in various studies, revealing an overlap in genetic susceptibility. The common biological pathways through lymphocyte-mediated immunity, JUN kinase activity, and tyrosine phosphorylation supports the role of immune dysfunction in MS and HL ( 7 ). A meta-analysis of genome-wide association studies (GWAS) has shown significant genetic overlap and found that the genetic determinants in the human leukocyte antigen (HLA) region govern the immune response to EBV. ( 7 ) This meta-analysis revealed significant genetic overlap between HL and MS, showing HL-associated single nucleotide polymorphisms (SNPs) to be linked to MS and subsequently, MS-associated SNPs to be linked to HL. This was prominently found in the HLA region of chromosome 6. The genetic analysis also suggested that EBV-positive HL and EBV-negative HL may be independently associated with MS, suggesting distinct etiological and genetic pathways. The shared biological pathways through B-cell and T-cell activation, immune cell signaling through the tyrosine phosphorylation and inflammation regulation through JUN kinase signaling indicates that immune hyperactivation is a common driver in both MS and HL. ( 7 ) Molecular mimicry from autoreactive CD4 + T-cells activated by EBV self-antigens is a key proposed mechanism in the pathogenesis of MS. This cross reactivity of T-cells with self-antigens in the CNS leads to autoimmune demyelination in animal models. ( 8 ) This supports the plausible theory that EBV may have a shared infectious trigger with molecular mimicry and immune dysregulation leading to the pathogenesis of HL and MS. Our reported case is unique because both MS and HL were diagnosed concurrently at the time of presentation. There have been case reports mentioning that HL and MS have occurred in the same patients after successful treatment of one of the conditions. Table 1 is a literature review of all published cases of MS and lymphoma co-occurring in the same patient. One case report describes a patient who developed MS 14 years after successful treatment of HL ( 9 ) while another illustrates a patient whose MS symptoms developed after 2 years following irradiation and chemotherapy for HL. ( 10 ) The elevation of Epstein-Barr virus nuclear antigen (EBNA) can be detected years before onset of MS, where EBNA-2 is found to have the strongest association. ( 11 ) This may serve as a prognostication biomarker for MS risk. In patients with HL, positive EBV serology was found in Reed-Sternberg cells detected by hybridization or immunohistochemistry. While EBV serology is not a standalone tool for diagnosis for MS and HL, it can be integrated to study genetic profiling and understanding therapies targeting EBV and preventing both conditions. Our patient presented with an atypical thoracic MRI finding of peripheral enhancement. This leads to a broader differential diagnosis to rule out other autoimmune disorders. Thus, a CT body was obtained which revealed a mediastinal mass. Even though MS was a leading differential, we had to obtain a biopsy to rule out other life-threatening possibilities like CNS lymphoma. There have been few case reports that have linked MS with CNS lymphoma. ( 12 , 13 ) No CNS lymphoma was found based on histopathological findings in our case. The treatment for MS does not clearly increase the risk of HL while HL immunotherapy, especially PD-1 inhibitors, may trigger CNS demyelination, mimicking MS. ( 14 ) After receiving treatment for HL, the symptoms of MS had partially remitted in our case and the patient remained clinical relapse-free until her 1 year follow up, but with evidence of ongoing subclinical imaging activity. Another case report also suggested a similar remission following aggressive chemotherapy for HL and remained disease activity-free for over six years. ( 15 ) Table 1 Descriptive summary of clinical evidence from case reports and case series Study Type of Study Cases Demographic Clinical Finding Management Conclusion Bellian et al., 1992 Case report 1 patient 31-year-old male, HL at age 17, presented with MS at age 31 HL in remission for 14 years before developing neurological symptoms diagnosed as MS. MS diagnosis was confirmed by typical clinical and paraclinical findings. HL: chemotherapy and radiotherapy (completed 14 years prior; achieved remission). MS: treated symptomatically (steroids for acute relapse). First documented case of an individual with HL and MS. Noted that HL and MS share similar epidemiologic features (young adult onset), suggesting a possible common etiologic factor. No DMT available in 1992. Habek et al., 2008 Case report 1 patient 21-year-old male with past history of IM and HL, presented with RRMS at age 24 No evidence of HL relapse. HL remained in remission. Developed spastic paraparesis that responded well to steroids. Over the following 3 years, had three relapses meeting criteria for RRMS. CSF showed oligoclonal bands and MS was confirmed. HL: Completed chemotherapy and radiotherapy 2 years before MS onset. MS: steroids for relapses. Started DMT after multiple relapses. Highlights a temporal association: HL (treated) followed by onset of MS. Study highlights that adult MS rarely occurs without prior EBV infection, suggesting EBV an ecological link in the pathogenesis of MS and HL. Rolls et al., 2010 Case series 5 patients 1. 20 years, male with HL, then RRMS 11 years later; 2. 31 years, female with MS with transmission to partner who developed NHL 5 yrs later; 3. 38 years, female with MS who developed NHL 25 yrs later; 4. 19 years, female with MS with HL 4 years later; 5. 33 years, female with EBV-positive NPC, then RRMS by 36. Two patients had MS and HL in the same individual (one with HL preceding MS by a decade, one with MS preceding HL by 4 years). The other cases showed MS in a patient with either non-Hodgkin lymphoma or NPC, or a close familial/partner occurrence of MS and lymphoma. All MS diagnoses were verified by McDonald criteria; all lymphomas and NPC confirmed histologically. HL: treated with standard chemotherapy. MS: managed with standard therapies. The authors found an unusual clustering of MS, HL, NHL, NPC and conclude that their study supports a possible association between MS and HL, NHL, NPC, likely through shared EBV-driven pathogenic mechanisms. They note that MS and HL share onset in young adult and familial clustering. CSF: Cerebrospinal fluid, DMT: disease-modifying therapy, EBV: Epstein Barr Virus, HL: Hodgkin lymphoma, IM: infectious mononucleosis, MS: Multiple Sclerosis, NHL: Non-Hodgkin lymphoma, NPC: Nasopharyngeal carcinoma, RRMS: Relapsing Remitting Multiple Sclerosis Conclusion We report a case of co-occurrence of MS with HL and note neurological stability after treatment with ABVD chemotherapy for HL. Although familial genetic clustering has been described, other potential common risk-factors between MS and HL are Epstein-Barr Virus infection and immunologic overlap, particularly in the context of lymphocyte-mediated immunity. The shared genetics and immunological interplay may explain overlaps, but MS and HL still remain distinct pathologies. Declarations Ethical approval and consent to participate Written informed consent was obtained from the patient for the consent to participate in this case report. A copy of written consent is available from the corresponding author on request. Consent for publication At the time of consent, the patient was fully oriented, cognitively intact, and fully capable of providing informed written consent for the publication of clinical details and any accompanying images. A copy of written consent is available from the corresponding author on request. Availability of data and materials The data and materials used during the current study are available from the corresponding author on request. Competing interests The authors declare that they have no competing interests. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Author’s contribution SR, PA, NGJ: conception, supervision, editing manuscript YK: design and drafting manuscript IG: editing manuscript Acknowledgement The authors would like to thank the Department of Neurology at Cleveland Clinic Florida for their support and contributions to this case report. 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Epub 2023 Apr 28. PMID: 37114502; PMCID: PMC10256986. Hjalgrim H, Rasmussen S, Rostgaard K, Nielsen NM, Koch-Henriksen N, Munksgaard L, Storm HH, Melbye M. Familial clustering of Hodgkin lymphoma and multiple sclerosis. J Natl Cancer Inst. 2004;96(10):780-4. 10.1093/jnci/djh135 . PMID: 15150306. Khankhanian P, Cozen W, Himmelstein DS, Madireddy L, van den Din L, Matsushita T, Glaser SL, Moré JM, Smedby KE, Baranzini SE, Mack TM, Lizée A, de Sanjosé S, Gourraud PA, Nieters A, Hauser SL, Cocco P, Maynadié M, Foretová L, Staines A, Delahaye-Sourdeix M, Li D, Bhatia S, Melbye M, Onel K, Jarrett R, McKay JD, Oksenberg JR, Hjalgrim H. Meta-analysis of genome-wide association studies reveals genetic overlap between Hodgkin lymphoma and multiple sclerosis. Int J Epidemiol. 2016;45(3):728–40. 10.1093/ije/dyv364 . Epub 2016 Mar 12. PMID: 26971321; PMCID: PMC5005944. Chastain EM, Miller SD. Molecular mimicry as an inducing trigger for CNS autoimmune demyelinating disease. 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Neuro Endocrinol Lett. 2008;29(6):867–70. PMID: 19112415. Oliveira MCB, de Brito MH, Simabukuro MM. Central Nervous System Demyelination Associated with Immune Checkpoint Inhibitors: Review of the Literature. Front Neurol. 2020;11:538695. 10.3389/fneur.2020.538695 . PMID: 33362680; PMCID: PMC7759512. Deery B, Anderson VA, Greenham M, Kornberg AJ. Multiple sclerosis and cancer: when two wrongs make a right? Dev Neurorehabil. 2014;17(3):147–55. 10.3109/17518423.2012.741148 . Epub 2013 Oct 8. PMID: 24102335. Additional Declarations No competing interests reported. Supplementary Files CarechecklistHLMS.pdf Cite Share Download PDF Status: Published Journal Publication published 13 Apr, 2026 Read the published version in BMC Neurology → Version 1 posted Editorial decision: Revision requested 05 Jan, 2026 Reviews received at journal 04 Jan, 2026 Reviewers agreed at journal 16 Dec, 2025 Reviews received at journal 03 Oct, 2025 Reviewers agreed at journal 10 Sep, 2025 Reviewers invited by journal 18 Aug, 2025 Editor assigned by journal 18 Aug, 2025 Editor invited by journal 31 Jul, 2025 Submission checks completed at journal 30 Jul, 2025 First submitted to journal 30 Jul, 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. 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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-7161237","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":504943496,"identity":"d2e929fe-26a6-41c2-b4c4-b6e4e009c379","order_by":0,"name":"Ipshita Garg","email":"","orcid":"","institution":"University of Texas Health Science Center","correspondingAuthor":false,"prefix":"","firstName":"Ipshita","middleName":"","lastName":"Garg","suffix":""},{"id":504943497,"identity":"4ea465a0-72fe-4112-a9c6-001236978590","order_by":1,"name":"Yugant Khand","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/klEQVRIiWNgGAWjYDCCAzAGDw+QYLMBEoyNB3CpRtHCA9GSBtLSQJKWw6hWYwN8tw+wSfP8ssuz5zl78HNB2Xm7te2HgbbU2ETj0iJ5LoFNmrcvuZgHSEjPOHc7eduZRKCWY2m5DTi0GJxhAGrpYU7s4ecxkOZtu51sdgCohbHhMCEt9SAtxr95284lm51/SIQWnh+HE3t4e8yAthywM7tBwBbJM4zNlnMbjif2nDljZs1zLjnB7AbQlgQ8fuE7w3zwxps/1YntPTnGt3nK7OzNzqc/fPChxganFmDEtUgwtiG4iWCVCTiVgwHzB4Y/CJ49fsWjYBSMglEwEgEApHhg8VGTVRwAAAAASUVORK5CYII=","orcid":"","institution":"Nepalese Army Institute of Health Sciences - College of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Yugant","middleName":"","lastName":"Khand","suffix":""},{"id":504943498,"identity":"48ed9477-5bab-4e92-b0d2-8332f9dac33d","order_by":2,"name":"Paunel Agyei","email":"","orcid":"","institution":"Cleveland Clinic Florida","correspondingAuthor":false,"prefix":"","firstName":"Paunel","middleName":"","lastName":"Agyei","suffix":""},{"id":504943499,"identity":"cb3d21e1-5cb9-4f6a-8639-0060ba03a123","order_by":3,"name":"Nestor Galvez-Jimenez","email":"","orcid":"","institution":"Baptist Health South Florida","correspondingAuthor":false,"prefix":"","firstName":"Nestor","middleName":"","lastName":"Galvez-Jimenez","suffix":""},{"id":504943500,"identity":"292dfb00-68c7-443a-8007-56372b84c3fb","order_by":4,"name":"Surabhi Ranjan","email":"","orcid":"","institution":"Cleveland Clinic Florida","correspondingAuthor":false,"prefix":"","firstName":"Surabhi","middleName":"","lastName":"Ranjan","suffix":""}],"badges":[],"createdAt":"2025-07-19 02:08:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7161237/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7161237/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12883-026-04889-3","type":"published","date":"2026-04-13T15:57:01+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":89984382,"identity":"34ca453c-8cfb-47c3-ae65-ce7f2a96389e","added_by":"auto","created_at":"2025-08-27 06:36:37","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":519445,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMRI Brain at initial diagnosis \u003c/strong\u003eA. 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T1 axial post-contrast showing patchy peripheral enhancement at T7 level.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7161237/v1/da5ef5441488ce2122549cd1.png"},{"id":89984388,"identity":"90e8f230-4d2e-4a60-ac6e-daafda7b1023","added_by":"auto","created_at":"2025-08-27 06:36:37","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1117458,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMRI Brain after 3 months\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eE. T2 FLAIR axial sequence. F. T1 post-contrast axial sequence, G.T2 FLAIR axial sequence, and H. T1 post-contrast axial sequence showing worsening contrast-enhanced lesions.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7161237/v1/9c89c5ec1e903d943bc103f0.png"},{"id":89984384,"identity":"7736a9d3-dcd5-4162-9f3a-cbdd3df0f78b","added_by":"auto","created_at":"2025-08-27 06:36:37","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":420402,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMRI Brain after 4 cycles of chemotherapy \u003c/strong\u003eI: T2 FLAIR axial sequence and J: T1 post-contrast axial sequence showed resolution of previous Gd-enhancing lesions but revealed a new enhancing focus in the left frontal lobe.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-7161237/v1/1de8140505d4ab11e650cbc9.png"},{"id":107350699,"identity":"f80596f9-0df0-4e70-b923-e4e961746843","added_by":"auto","created_at":"2026-04-20 16:00:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3651407,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7161237/v1/b5c9ecf4-b479-4e4f-8ff3-71a2dc7e95cd.pdf"},{"id":89984381,"identity":"de5249ca-7603-4736-a694-a42410891f85","added_by":"auto","created_at":"2025-08-27 06:36:37","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":1251721,"visible":true,"origin":"","legend":"","description":"","filename":"CarechecklistHLMS.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7161237/v1/af6d81dc13632c9ffc6a7116.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Exploring a possible shared pathophysiology in co-occurrence of multiple sclerosis and Hodgkin lymphoma: a case report and review of literature","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMultiple sclerosis (MS) is a chronic autoimmune demyelinating disorder of the central nervous system, while Hodgkin lymphoma (HL) is a monoclonal lymphoid neoplasm, commonly arising in the cervical lymph nodes. MS and HL share certain common genetics, epidemiology traits, and immunological factors. Both affect immune activation, cell proliferation and lymphocyte-mediated immunity. (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) The two seemingly distinct diseases have similarities in age distribution, geographical patterns and potential risk factors. However, co-occurrence of these two distinct clinical conditions is rare. While the exact mechanism behind this is poorly understood, shared factors such as genetic susceptibility, Epstein Barr virus (EBV), and variable presentations indicating a relationship between their treatments and relapses may provide insight into potential new diagnostic and therapeutic strategies. (\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e–\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) We report a case of a woman who presented with neurological deficits along with systemic symptoms fulfilling criteria for MS with synchronous HL. This case explores a potential overlap due to shared immunopathogenesis between the occurrence of MS and HL.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 37-year-old previously healthy woman presented to the neurology clinic with a one-week history of progressive bilateral lower limb weakness, numbness, and new-onset urinary retention. She also complained of night sweats, 25-pound unintentional weight loss, and loss of appetite which preceded her neurological symptoms by three weeks. She reported persistent tingling and numbness in both legs which ascended from her feet to her thighs. She also reported an inability to sense bladder fullness leading to episodes of incomplete voiding. She denied fever, recent infections, or prior neurologic symptoms. Her medical history was unremarkable for prior autoimmune or neoplastic diagnoses. She did not smoke or use illicit substances. She had no family history for neurological or oncologic disease. On examination, she was alert and oriented with normal higher cortical functions. Cranial nerves were intact. Motor examination revealed symmetric leg weakness with Medical Research Council score of 4/5. There was an increased tone, spasticity and hyperreflexia with sustained clonus. A left-sided extensor plantar response was noted. Sensory testing showed reduced vibration and proprioception in her feet with preserved pinprick and temperature sensation. She had a spastic and broad-based gait. Bladder ultrasound confirmed urinary retention with elevated post-void residual volumes. She had normal upper extremity coordination. Magnetic resonance imaging (MRI) of the brain with gadolinium (Gd) contrast showed multiple non-enhancing hyperintense lesions in the periventricular and juxtacortical white matter. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eMRI of the thoracic spine revealed patchy peripheral gadolinium-enhancing lesions within the spinal cord. Figure\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eCerebrospinal fluid (CSF) analysis had increased immunoglobulin G (IgG) and oligoclonal bands. She had positive IgG antibodies to JC virus and Epstein-Barr virus (EBV) with negative IgM. The serology testing suggested past exposure without any acute infection. A further workup was planned for alternative or co-existing etiologies due to her unusual peripheral enhancement of the thoracic cord and systemic symptoms. Three-months later, a follow-up MRI brain showed worsening contrast-enhanced lesions. Figure\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003c/p\u003e\u003cp\u003eA repeat CSF study revealed normal OCBs and IgG index and CSF was negative for malignant cells, JCV DNA, and EBV DNA. A computed tomography (CT) scan of the chest, abdomen and pelvis showed a large anterior mediastinal mass with extensive mediastinal lymphadenopathy. A lymph node biopsy was performed which confirmed the diagnosis of classic Hodgkin lymphoma (HL). A stereotactic brain biopsy of the enhancing lesion was performed to assess the possibility of central nervous system involvement by lymphoma. The biopsy findings showed gliosis and perivascular lymphocytic infiltrates without evidence of malignant cells. The patient was diagnosed with relapsing-remitting multiple sclerosis (RRMS) and classic HL. She initially received intravenous methylprednisolone for five days which showed mild improvement in lower limb strength and sensory symptoms. She was initiated on standard ABVD chemotherapy (doxorubicin, bleomycin, vinblastine, and dacarbazine) given her diagnosis of HL. A follow-up brain MRI showed resolution of previous Gd-enhancing lesions but revealed a new enhancing focus in the left frontal lobe even after completing four cycles of chemotherapy which was consistent with her ongoing demyelinating activity. Figure\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e4\u003c/span\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eHer clinical condition remained stable despite the new lesion. She completed a full course of six ABVD cycles. On her follow-up, a positron emission tomography (PET) scan showed residual bulky disease in the chest. She was treated with proton beam radiation therapy to the mediastinum for three months after completion of chemotherapy. During her one-year follow-up, brain MRI showed no new contrast-enhancing lesions but revealed five new supratentorial T2-FLAIR hyperintense lesions which suggested subclinical disease activity. The patient complained of ongoing fatigue, transient short-term memory difficulties, and mild residual numbness in her feet. She remained ambulatory and independent in activities of daily living. Due to ongoing HL surveillance and concerns regarding immunosuppression, she was not started on disease-modifying therapy for MS. She remains under multidisciplinary care by hematology-oncology, neuro-oncology and rehabilitation teams.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe overall risk of cancer in multiple sclerosis (MS) patients is lower, but Hodgkin\u0026rsquo;s lymphoma (HL) is an exception, though statistical significance was lacking. (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) The co-occurrence was initially observed by Newell in 1970, where he noted an epidemiological relation to MS and HL. (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) Some studies have strong evidence linking Epstein-Barr Virus (EBV) to MS and lymphoproliferative cancer, including HL and certain non-Hodgkin\u0026rsquo;s lymphoma (NHL), reinforcing its role as a causative organism with delayed complications. While the acceleration of MS occurs as a late complication of EBV infection, lymphoma risk peaks within 2 years after primary EBV exposure. (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) The shared epidemiological traits between MS and HL, particularly young adult-onset Hodgkin lymphoma (YAHL) is hypothesized with childhood exposure to EBV. The Swedish National cohort study by Montgomery et al. found a statistically significant association between MS and risk of YAHL. (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) This association was 3.3 times higher in females, possibly due to higher MS prevalence in that subset of population. (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) This underscores EBV\u0026rsquo;s pathogenic role highlighting immune dysregulation as a potential bridge between MS and HL. These suggest that EBV might play a role in development of both HL and MS, as a smoldering autoimmune process.\u003c/p\u003e\u003cp\u003eA positive EBV serology was present in our patient and could indicate a common immunological precursor to the diagnosis of HL and MS in this case. However, studies fail to account for ethnicity or cannot pinpoint a particular infectious exposure during childhood which could have the development of YAHL. Another study hypothesized that HL and MS share similar geographic distributions. A cross-sectional analysis from 21 countries concluded that HL and MS were common in European countries and showed the inter-age correlation for HL started at age 5 or less while MS only started at age 15 years. (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) This supports the contention that environmental factors influence the occurrence of HL earlier than MS. There are established studies indicating exposure to sunlight and low serum levels of vitamin D in the occurrence of MS. The role of vitamin D in HL remains unexplored. A Danish population-based cancer registry also concluded that environmental factors are a probable explanation to the familial clustering of MS and HL which also correlates to Newell\u0026rsquo;s hypothesis. (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eThe co-occurrence of HL and MS cannot be explained with environmental factors alone. The relationship between HL and MS has been explored in various studies, revealing an overlap in genetic susceptibility. The common biological pathways through lymphocyte-mediated immunity, JUN kinase activity, and tyrosine phosphorylation supports the role of immune dysfunction in MS and HL (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). A meta-analysis of genome-wide association studies (GWAS) has shown significant genetic overlap and found that the genetic determinants in the human leukocyte antigen (HLA) region govern the immune response to EBV. (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) This meta-analysis revealed significant genetic overlap between HL and MS, showing HL-associated single nucleotide polymorphisms (SNPs) to be linked to MS and subsequently, MS-associated SNPs to be linked to HL. This was prominently found in the HLA region of chromosome 6. The genetic analysis also suggested that EBV-positive HL and EBV-negative HL may be independently associated with MS, suggesting distinct etiological and genetic pathways. The shared biological pathways through B-cell and T-cell activation, immune cell signaling through the tyrosine phosphorylation and inflammation regulation through JUN kinase signaling indicates that immune hyperactivation is a common driver in both MS and HL. (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) Molecular mimicry from autoreactive CD4\u0026thinsp;+\u0026thinsp;T-cells activated by EBV self-antigens is a key proposed mechanism in the pathogenesis of MS. This cross reactivity of T-cells with self-antigens in the CNS leads to autoimmune demyelination in animal models. (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) This supports the plausible theory that EBV may have a shared infectious trigger with molecular mimicry and immune dysregulation leading to the pathogenesis of HL and MS.\u003c/p\u003e\u003cp\u003eOur reported case is unique because both MS and HL were diagnosed concurrently at the time of presentation. There have been case reports mentioning that HL and MS have occurred in the same patients after successful treatment of one of the conditions. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e is a literature review of all published cases of MS and lymphoma co-occurring in the same patient. One case report describes a patient who developed MS 14 years after successful treatment of HL (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) while another illustrates a patient whose MS symptoms developed after 2 years following irradiation and chemotherapy for HL. (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e) The elevation of Epstein-Barr virus nuclear antigen (EBNA) can be detected years before onset of MS, where EBNA-2 is found to have the strongest association. (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) This may serve as a prognostication biomarker for MS risk. In patients with HL, positive EBV serology was found in Reed-Sternberg cells detected by hybridization or immunohistochemistry. While EBV serology is not a standalone tool for diagnosis for MS and HL, it can be integrated to study genetic profiling and understanding therapies targeting EBV and preventing both conditions. Our patient presented with an atypical thoracic MRI finding of peripheral enhancement. This leads to a broader differential diagnosis to rule out other autoimmune disorders. Thus, a CT body was obtained which revealed a mediastinal mass. Even though MS was a leading differential, we had to obtain a biopsy to rule out other life-threatening possibilities like CNS lymphoma. There have been few case reports that have linked MS with CNS lymphoma. (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) No CNS lymphoma was found based on histopathological findings in our case. The treatment for MS does not clearly increase the risk of HL while HL immunotherapy, especially PD-1 inhibitors, may trigger CNS demyelination, mimicking MS. (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e) After receiving treatment for HL, the symptoms of MS had partially remitted in our case and the patient remained clinical relapse-free until her 1 year follow up, but with evidence of ongoing subclinical imaging activity. Another case report also suggested a similar remission following aggressive chemotherapy for HL and remained disease activity-free for over six years. (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e)\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDescriptive summary of clinical evidence from case reports and case series\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStudy\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eType of Study\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCases\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eDemographic\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eClinical Finding\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eManagement\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eConclusion\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBellian et al., 1992\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCase report\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 patient\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e31-year-old male, HL at age 17, presented with MS at age 31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eHL in remission for 14 years before developing neurological symptoms diagnosed as MS.\u003c/p\u003e\u003cp\u003eMS diagnosis was confirmed by typical clinical and paraclinical findings.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eHL: chemotherapy and radiotherapy (completed 14 years prior; achieved remission).\u003c/p\u003e\u003cp\u003eMS: treated symptomatically (steroids for acute relapse).\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eFirst documented case of an individual with HL and MS.\u003c/p\u003e\u003cp\u003eNoted that HL and MS share similar epidemiologic features (young adult onset), suggesting a possible common etiologic factor. No DMT available in 1992.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHabek et al., 2008\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCase report\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 patient\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e21-year-old male with past history of IM and HL, presented with RRMS at age 24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNo evidence of HL relapse. HL remained in remission. Developed spastic paraparesis that responded well to steroids.\u003c/p\u003e\u003cp\u003eOver the following 3 years, had three relapses meeting criteria for RRMS.\u003c/p\u003e\u003cp\u003eCSF showed oligoclonal bands and MS was confirmed.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eHL: Completed chemotherapy and radiotherapy 2 years before MS onset.\u003c/p\u003e\u003cp\u003eMS: steroids for relapses. Started DMT after multiple relapses.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eHighlights a temporal association: HL (treated) followed by onset of MS. Study highlights that adult MS rarely occurs without prior EBV infection, suggesting EBV an ecological link in the pathogenesis of MS and HL.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRolls et al., 2010\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCase series\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5\u003c/p\u003e\u003cp\u003epatients\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1. 20 years, male with HL, then RRMS 11 years later;\u003c/p\u003e\u003cp\u003e2. 31 years, female with MS with transmission to partner who developed NHL 5 yrs later;\u003c/p\u003e\u003cp\u003e3. 38 years, female with MS who developed NHL 25 yrs later;\u003c/p\u003e\u003cp\u003e4. 19 years, female with MS with HL 4 years later;\u003c/p\u003e\u003cp\u003e5. 33 years, female with EBV-positive NPC, then RRMS by 36.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTwo patients had MS and HL in the same individual (one with HL preceding MS by a decade, one with MS preceding HL by 4 years). The other cases showed MS in a patient with either non-Hodgkin lymphoma or NPC, or a close familial/partner occurrence of MS and lymphoma.\u003c/p\u003e\u003cp\u003eAll MS diagnoses were verified by McDonald criteria; all lymphomas and NPC confirmed histologically.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eHL: treated with standard chemotherapy.\u003c/p\u003e\u003cp\u003eMS: managed with standard therapies.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eThe authors found an unusual clustering of MS, HL, NHL, NPC and conclude that their study supports a possible association between MS and HL, NHL, NPC, likely through shared EBV-driven pathogenic mechanisms. They note that MS and HL share onset in young adult and familial clustering.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e\u003cp\u003eCSF: Cerebrospinal fluid, DMT: disease-modifying therapy, EBV: Epstein Barr Virus, HL: Hodgkin lymphoma, IM: infectious mononucleosis, MS: Multiple Sclerosis, NHL: Non-Hodgkin lymphoma, NPC: Nasopharyngeal carcinoma, RRMS: Relapsing Remitting Multiple Sclerosis\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eWe report a case of co-occurrence of MS with HL and note neurological stability after treatment with ABVD chemotherapy for HL. Although familial genetic clustering has been described, other potential common risk-factors between MS and HL are Epstein-Barr Virus infection and immunologic overlap, particularly in the context of lymphocyte-mediated immunity. The shared genetics and immunological interplay may explain overlaps, but MS and HL still remain distinct pathologies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for the\u0026nbsp;consent to participate in this case report. A copy of written consent is available from the corresponding author on request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAt the time of consent, the\u0026nbsp;patient was fully oriented, cognitively intact, and fully capable of providing informed written consent for\u0026nbsp;the publication of clinical details and any accompanying images. A copy of written consent is available from the corresponding author on request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data and materials used during the current study are available from the corresponding author on request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor’s contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSR, PA, NGJ: conception, supervision, editing manuscript\u003c/p\u003e\n\u003cp\u003eYK: design and drafting manuscript\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIG: editing manuscript\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank the Department of Neurology at Cleveland Clinic Florida for their support and contributions to this case report.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMontgomery S, Hajiebrahimi M, Burkill S, Hillert J, Olsson T, Bahmanyar S. 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Multiple sclerosis and cancer: when two wrongs make a right? Dev Neurorehabil. 2014;17(3):147\u0026ndash;55. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3109/17518423.2012.741148\u003c/span\u003e\u003cspan address=\"10.3109/17518423.2012.741148\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2013 Oct 8. PMID: 24102335.\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":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Multiple sclerosis, Hodgkin lymphoma, neuro-oncology, neuro-immunology, case report","lastPublishedDoi":"10.21203/rs.3.rs-7161237/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7161237/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eINTRODUCTION\u003c/b\u003e\u003c/p\u003e\u003cp\u003eMultiple sclerosis (MS) and Hodgkin lymphoma (HL) share common epidemiology, genetics and immunological factors. We report a case of a woman who presented with neurological deficits along with systemic symptoms fulfilling criteria for MS with synchronous HL.\u003c/p\u003e\u003cp\u003e\u003cb\u003eCASE PRESENTATION\u003c/b\u003e\u003c/p\u003e\u003cp\u003eA 37-year-old woman presented with bilateral leg weakness, numbness and urinary retention which was preceded by three weeks of night sweats, 25-pound weight loss and anorexia. Neurological examination showed spastic paraparesis, sensory deficit and a left extensor plantar response. A magnetic resonance imaging (MRI) of brain showed multiple non-enhancing white-matter lesions, with patchy areas of peripheral gadolinium (Gd)-enhancement in the thoracic cord. Serology was positive for JC and EBV IgG antibodies. Body imaging revealed a mediastinal mass, and biopsy confirmed classical HL. The patient was given steroid infusions which resulted in mild improvements of leg weakness and numbness. She was started on doxorubicin, bleomycin, dacarbazine and vinblastine (ABVD) for HL. A Gd-enhanced MRI brain obtained after 4 cycles of ABVD showed resolution of enhancing lesions but new T2-FLAIR lesion consistent with active MS. Due to ongoing HL surveillance and concerns regarding immunosuppression, she was not started on disease-modifying therapy for MS. On her annual follow-up, she reported persistent fatigue, transient memory deficit and residual leg numbness.\u003c/p\u003e\u003cp\u003e\u003cb\u003eDISCUSSION\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe relationship between HL and MS has been explored in various studies, revealing an overlap in genetic susceptibility, shared biological pathways through lymphocyte-mediated immunity, JUN kinase activity, and tyrosine phosphorylation, and common environmental factors, such as the presence of EBV. Our patient presented with an atypical thoracic MRI finding of peripheral enhancement which led to further investigation and diagnosis of HL. The concurrent occurrence of MS and HL may point toward shared immune dysregulation.\u003c/p\u003e\u003cp\u003e\u003cb\u003eCONCLUSION\u003c/b\u003e\u003c/p\u003e\u003cp\u003eWe report a case of co-occurrence of MS with HL and note neurological stability after treatment with ABVD chemotherapy for HL. The shared genetics and immunological interplay may explain overlaps, but MS and HL still remain distinct pathologies.\u003c/p\u003e","manuscriptTitle":"Exploring a possible shared pathophysiology in co-occurrence of multiple sclerosis and Hodgkin lymphoma: a case report and review of literature","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-27 06:36:32","doi":"10.21203/rs.3.rs-7161237/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-01-05T07:04:12+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-04T18:07:10+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"300849982263639289516464549505938209337","date":"2025-12-16T09:23:33+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-03T14:32:13+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"19189437491044918832347307351460724135","date":"2025-09-10T15:44:53+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-18T11:09:14+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-18T10:48:19+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-07-31T14:26:32+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-30T23:40:49+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Neurology","date":"2025-07-30T23:38:27+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1a8afdc7-e4a4-4a0b-96ee-bb07851aaf10","owner":[],"postedDate":"August 27th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-04-20T16:00:09+00:00","versionOfRecord":{"articleIdentity":"rs-7161237","link":"https://doi.org/10.1186/s12883-026-04889-3","journal":{"identity":"bmc-neurology","isVorOnly":false,"title":"BMC Neurology"},"publishedOn":"2026-04-13 15:57:01","publishedOnDateReadable":"April 13th, 2026"},"versionCreatedAt":"2025-08-27 06:36:32","video":"","vorDoi":"10.1186/s12883-026-04889-3","vorDoiUrl":"https://doi.org/10.1186/s12883-026-04889-3","workflowStages":[]},"version":"v1","identity":"rs-7161237","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7161237","identity":"rs-7161237","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}