Infiltrating Tumor vs Demyelination Disorders: Case Study of Two Adults

Infiltrating Tumor vs Demyelination Disorders: Case Study of Two Adults | 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 Infiltrating Tumor vs Demyelination Disorders: Case Study of Two Adults Harsh Patel, Preeti Singh, Abhaya Kumar This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8126271/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 Long-segment intramedullary spinal cord lesions pose a unique diagnostic and therapeutic dilemma from a neurosurgical perspective. For the operating surgeon, the central challenge lies in distinguishing infiltrative intramedullary tumors from inflammatory demyelinating pathologies, as both may mimic each other clinically and radiologically. This distinction is critical: while early biopsy or decompressive surgery may be warranted for progressive neoplasms, unnecessary intervention in demyelinating disorders can result in avoidable morbidity in an already high-risk spinal cord environment. This report details two diagnostically challenging adult cases encountered in neurosurgical practice—one ultimately proven to be a Grade III spinal astrocytoma requiring definitive surgical management, and the other a neuromyelitis optica spectrum disorder (NMOSD) masquerading as a spinal cord tumor. By comparing their clinical progression, operative considerations, intraoperative neurophysiology, radiological subtleties, and final diagnoses, we highlight key decision points that influence whether to operate, observe, or pursue advanced immunologic testing. The aim is to provide neurosurgeons with a practical reference when faced with similar long-segment intramedullary lesions, underscoring the profound impact that early diagnostic accuracy has on surgical planning, neurological outcomes, and long-term patient quality of life. Neurosurgery infiltrating demyelination tumor NMOSD intramedullary astrocytoma Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Long-segment cervical spinal cord lesions frequently blur the diagnostic boundaries between neoplastic and inflammatory etiologies, creating significant challenges for neurosurgeons tasked with determining when surgical intervention is warranted. Infiltrative intramedullary tumors—particularly astrocytomas—may closely resemble inflammatory demyelinating disorders such as NMOSD, tumefactive demyelination, or MOG-associated disease. This overlap is compounded by similarities in radiological features, including enhancement patterns, metabolic activity on PET-CT, and varying degrees of cord expansion, any of which may misleadingly suggest a neoplastic process. Such ambiguity can result in critical clinical consequences, ranging from unnecessary or overly aggressive surgery in a demyelinating condition to delayed biopsy and tumor treatment when malignancy is present. These two cases highlight the subtle clinical cues, radiological discriminators, and multidisciplinary reasoning essential for navigating this diagnostic grey zone. They underscore the importance of integrating neurosurgical judgment with immunological and radiological expertise to ensure timely, accurate diagnosis and optimal patient outcomes. Case 1: High‑Grade Spinal Astrocytoma A middle-aged female presented with progressively worsening neck pain accompanied by limb weakness and gait imbalance over several weeks. There was no history of trauma, fever, weight loss, or preceding infection to suggest an alternative systemic cause. As her condition evolved, she developed acute urinary retention and constipation, indicating emerging high-grade cervical myelopathy and prompting urgent neurosurgical evaluation. Clinical Examination On examination, the patient was alert, oriented, and cooperative. Motor testing revealed asymmetric quadriparesis, with increased tone in the lower limbs and variable tone in the upper limbs. Deep tendon reflexes were brisk throughout, and bilateral extensor plantar responses were elicited. Cranial nerve function remained intact. Overall, the neurological profile was consistent with upper motor neuron involvement localizing to the cervical spinal cord. Laboratory Investigations Laboratory evaluation showed hemoglobin of 14.4 g/dL, leukocytosis with a WBC count of 13,600/µL, and normal platelet levels. CRP was mildly elevated at 6.7 mg/L, while liver function tests were within normal limits. Serum total protein was slightly reduced at 5.7 g/dL with an albumin level of 4.05 g/dL. Cerebrospinal fluid analysis revealed 1 WBC/µL, 6 RBCs/µL, elevated protein at 79 mg/dL, and glucose of 66 mg/dL. Serological testing for NMO-IgG, MOG-IgG, and vasculitis markers was negative. Overall, despite comprehensive laboratory, CSF, and serological evaluation, no definitive inflammatory or autoimmune etiology was identified. Radiological Evaluation Figure 1: MRI Cervical Spine showing a long-segment intramedullary T₂ hyperintensity extending from C2 to C5, associated with cord expansion MRI Spine MRI of the cervical spine demonstrated a long-segment intramedullary T₂ hyperintensity extending from C2 to C5, associated with cord expansion and patchy, faint post-contrast enhancement. Additionally, a mild altered signal was noted in the upper thoracic segments (T2–T4). The radiological impression predominantly favored an inflammatory or immune-mediated demyelinating process; however, the possibility of an infiltrative neoplasm could not be excluded . PET-CT PET-CT demonstrated linear increased metabolic activity extending from C2 to C5, corresponding to the region of T₂ hyperintensity on MRI. While this uptake pattern supported active pathology within the cervical cord, it remained nonspecific and did not conclusively distinguish between an inflammatory demyelinating process and an infiltrative neoplasm. Initial Management The patient was initiated on high-dose intravenous methylprednisolone for three days; however, her neurological status deteriorated, with new-onset acute urinary retention, constipation, and progressive limb weakness. In view of steroid failure, she subsequently received intravenous immunoglobulin (2 g/kg over five days), but no clinical improvement was observed. Neurosurgical Referral & Decision-Making Due to progressive decline despite immunotherapy and the possibility of neoplasm, the patient was referred to neurosurgery.A decision was made to perform surgical debulking and biopsy of the lesion. Surgical Intervention A debulking biopsy of the intramedullary lesion was performed.There were no intraoperative complications. The patient was continued on postoperative intravenous steroids. Figure 2 a) Intra operative image before and after tumor removal b)Pre and post operative MRI Histopathology Findings Figure 3 : Histopathological examination Histopathological examination confirmed a WHO Grade III spinal astrocytoma. The lesion demonstrated a hypercellular glial neoplasm with marked nuclear atypia, increased mitotic activity, and an infiltrative growth pattern. Immunohistochemistry showed strong GFAP positivity, supporting its glial origin. These features collectively established the diagnosis of a high-grade infiltrating astrocytoma. Postoperative Course Postoperatively, the patient showed no significant neurological recovery. Instead, she progressed to spastic quadriparesis and remained severely functionally impaired, requiring full assistance for activities of daily living. Further Management The patient subsequently underwent 25 cycles of radiation therapy along with intensive physiotherapy and occupational therapy. She was also initiated on Lokomat-assisted robotic gait training in an effort to optimize functional recovery. A urology consultation was obtained for persistent neurogenic bladder dysfunction, resulting in the placement of a suprapubic cystostomy. Despite comprehensive rehabilitation and multimodal supportive care, her neurological improvement remained minimal, reflecting the aggressive and infiltrative nature of the underlying tumor. Case 2: Demyelinating Pseudotumor – Neuromyelitis Optica Spectrum Disorder (NMOSD) A 47-year-old male presented with sudden-onset weakness of the right lower limb, which progressed to involve the right upper limb over a 15-day period. The deficits evolved steadily without any preceding trauma, fever, constitutional symptoms, or visual disturbances to suggest optic neuritis or other systemic involvement. Clinical Examination On examination, the patient was conscious, oriented, and hemodynamically stable, with intact cranial nerve function. Motor testing revealed asymmetric weakness, with power of 3/5 in the right upper limb and 4/5 in the right lower limb, accompanied by reduced tone on the right side. Deep tendon reflexes were exaggerated on the right, including the biceps, triceps, supinator, knee, and ankle jerks. Mild upper cervical tenderness was noted at the C1–C2 level. Sensory examination showed no clear modality dissociation, and bowel and bladder functions were preserved at the time of presentation. Radiological Evaluation MRI Cervical Spine Figure 4: MRI demonstrated long-segment involvement of the cervicomedullary junction and upper cervical cord, with diffuse holocord swelling and patchy eccentric enhancement. Small intramedullary cysts were noted at the C1–C2 level. The overall radiological appearance strongly suggested an infiltrative intramedullary neoplasm, particularly an astrocytoma or ependymoma. However, PET-CT revealed no corresponding metabolically active lesion, creating a notable discordance between structural and metabolic imaging and raising uncertainty regarding the underlying pathology. Initial Management The patient was treated with high-dose intravenous methylprednisolone; however, no meaningful clinical improvement was observed. In view of the persistent deficits and MRI findings highly suggestive of an intramedullary neoplasm, a surgical biopsy was undertaken to establish a definitive diagnosis. Surgical Intervention A total C3–C4 laminectomy with biopsy of the intramedullary lesion was performed under intraoperative neuromonitoring (IONM). No gross tumor mass was visualized intraoperatively. Figure 5 : Intraoperative image Post-operative Course Postoperatively, the patient developed recurrent paroxysmal dystonic episodes involving the face and right-sided limbs, each lasting 5–6 seconds. These events increased progressively in frequency and were accompanied by worsening right hemiparesis, marking a significant deterioration in his neurological status. Histopathological Findings Initial histopathological evaluation suggested a demyelinating pseudotumor characterized by reactive gliosis, without definitive neoplastic cells. Certain features resembled therapy-related changes sometimes seen in lymphomas following corticosteroid exposure, contributing to diagnostic ambiguity. A subsequent expert review, however, confirmed a non-neoplastic inflammatory demyelinating process, with no evidence of astrocytoma, lymphoma, or ependymoma, thereby establishing the diagnosis of an inflammatory demyelinating lesion rather than an infiltrative tumor. Figure 6: Histopathological Examination Further Diagnostic Testing A neurology consultation was sought, and serological testing revealed a positive serum NMO-IgG (AQP4 antibody), while the ANA profile and ACE levels were within normal limits. Although the patient exhibited no clinically overt optic neuritis, the presence of longitudinally extensive transverse myelitis together with NMO antibody positivity established the diagnosis of neuromyelitis optica spectrum disorder (NMOSD) presenting as a demyelinating pseudotumor. Definitive Management The patient was managed with continuation of intravenous corticosteroids, followed by five cycles of plasmapheresis in view of persistent neurological deficits. He concurrently underwent intensive physiotherapy and occupational therapy to address functional decline. During follow-up, rituximab immunotherapy was initiated as long-term disease-modifying treatment for NMOSD. Outcome The patient remained stable and demonstrated partial neurological recovery , with reduction in dystonic episodes and improved right-sided motor function over subsequent weeks. At follow-up, he achieved meaningful functional gains with continued rehabilitation and immunotherapy. Comparative Discussion Both cases initially exhibited overlapping radiological features, including long-segment T2 hyperintensity, cord expansion, and patchy enhancement, making early differentiation challenging. However, several discriminative clues emerged during evaluation. Demyelinating lesions characteristically demonstrate open-ring or incomplete enhancement patterns, whereas neoplastic lesions more often present with closed, nodular, or homogeneous enhancement. PET-CT, although useful, may be misleading, as inflammatory activity can mimic hypermetabolism typically associated with tumors. Clinical trajectories also diverge: infiltrative tumors tend to show relentless neurological deterioration, whereas inflammatory lesions may fluctuate or show partial response to immunotherapy. Ultimately, when imaging and clinical features remain ambiguous, histopathological examination remains the most reliable method for establishing a definitive diagnosis. Discussion Long-segment intramedullary spinal cord lesions, especially those involving the cervical region, remain a profound diagnostic challenge. As illustrated by our two cases, the differential diagnosis frequently includes both neoplastic processes (such as astrocytoma or ependymoma) and inflammatory demyelinating disorders (such as NMOSD). The implications of misdiagnosis are substantial, given that therapeutic strategies diverge sharply: neoplasms often require surgical intervention, whereas demyelinating lesions generally respond to immunotherapy [ 1 , 2 ]. Radiological Features and Diagnostic Pitfalls Magnetic resonance imaging (MRI) is the cornerstone of evaluation for intramedullary spinal cord lesions. However, despite its sensitivity, MRI lacks absolute specificity. Astrocytomas and ependymomas can both present as long-segment T2-hyperintense lesions with cord expansion and contrast enhancement, overlapping significantly with inflammatory etiologies [ 11 ]. Distinguishing features on MRI have been described: ependymomas often exhibit a “cap sign,” central location, syringohydromyelia, and diffuse enhancement, whereas astrocytomas may show eccentric location, heterogeneous enhancement, and satellite cysts [ 9 ]. Enhancement patterns also yield important clues: inflammatory demyelination more often demonstrates open-ring or incomplete-ring enhancement, whereas neoplastic lesions frequently show closed, nodular, or solid enhancement [ 4 ]. The “lens-shaped” enhancement on sagittal sequences has even been reported in NMOSD in some cases [ 4 ]. Nevertheless, reliance on MRI alone can mislead: pseudotumoral demyelination may mimic tumoral growth, and surgical intervention based solely on imaging may be fraught with risk [ 14 ]. PET-CT, while increasingly used as an adjunct, may also mislead. Inflammatory lesions can show metabolic activity, resulting in false positives for neoplastic disease [ 4 ]. Emerging tools like deep learning-based MRI segmentation and classification have shown promise in differentiating tumors from demyelination; for example, a recent model achieved high accuracy in distinguishing astrocytoma vs. NMOSD vs. ependymoma using T2-weighted MRI [ 3 ]. Nonetheless, these remain investigational and cannot yet replace histological diagnosis in ambiguous cases. Role of Serology and Clinical Correlation The clinical trajectory and serological markers provide additional, often decisive, information. NMOSD is strongly associated with aquaporin-4 (AQP4) antibodies, and longitudinally extensive transverse myelitis (LETM) involving ≥ 3 vertebral segments is a hallmark [ 16 ]. However, lesion length alone is insufficient to confirm NMOSD: various pathological processes—including neoplasia, sarcoidosis, and vascular lesions—can produce LETM-like MRI appearances [ 16 , 17 ]. Positive AQP4 serology in the absence of optic neuritis has been well described, and a diagnosis of NMOSD may be established based on MRI and serology even without optic nerve involvement, as in our second case [ 16 , 15 ]. Conversely, neoplastic lesions typically follow a more insidious but relentless clinical decline, though exceptions exist. Paraneoplastic processes and metastases (though rare) must also be kept in mind, especially in patients without typical demyelinating features [ 6 , 7 ]. Indeed, intramedullary spinal cord metastases (ISCM) are rare but increasingly reported; newer case reports have documented lesions mimicking astrocytoma on imaging but later proven to be metastatic carcinoma [ 7 , 8 ]. Histopathological Confirmation Given the overlapping clinical and imaging features, histopathology frequently remains the definitive arbiter. Intraoperative frozen-section diagnosis is commonly used but less reliable in spinal cord tumors compared to intracranial ones; accuracy for ependymoma vs. astrocytoma can be as low as ~ 70% [ 2 ]. Moreover, technique and sample adequacy strongly influence the result. The neurosurgical decision-making process, therefore, must factor in not only imaging and intraoperative findings but also the surgeon’s judgment about the risks and benefits of biopsy versus resection [ 1 , 2 ]. Therapeutic Implications and Outcomes Management strategies diverge markedly upon diagnosis. For primary intramedullary tumors such as ependymoma, gross total resection (GTR) can often be achieved, and is associated with better outcomes [ 12 ]. In contrast, astrocytomas, especially high-grade, are more infiltrative and less amenable to complete resection, and the extent of resection may not correlate well with survival [ 12 ]. For inflammatory demyelinating lesions like NMOSD, high-dose steroids, plasmapheresis, and long-term immunotherapy (e.g., rituximab) are the mainstays [ 15 , 16 ]. Early initiation of therapy can arrest or even reverse clinical decline if correctly diagnosed. Multidisciplinary Approach and Emerging Directions These cases highlight the essential need for a multidisciplinary team (neurosurgeons, neurologists, radiologists, pathologists) in the evaluation of ambiguous intramedullary lesions. Clinical history, radiology, serology, intraoperative findings, and pathology must be concordant, and discrepancies should prompt reconsideration rather than premature intervention [ 14 ]. Emerging modalities may further aid diagnosis. Deep learning-based image analysis has shown strong performance in lesion classification [ 3 ]. Advanced MRI techniques—such as diffusion kurtosis imaging (DKI) and magnetization-transfer imaging—also provide microstructural insights into tissue integrity and myelin status, potentially offering non-invasive biomarkers of demyelination versus neoplasia [ 19 , 20 ]. Finally, immunotherapy for spinal cord gliomas (e.g., glioma immunotherapy) is being explored, though challenges remain due to the blood–spinal cord barrier and tumor heterogeneity [ 13 ]. Limitations and Future Considerations Our report is limited by its small sample size (two cases) and retrospective nature. While we provide a detailed narrative, the generalizability is constrained. Larger studies or registries are needed to better characterize imaging features, clinical trajectories, and outcomes of tumor vs. pseudotumor in intramedullary spinal disease. Furthermore, prospective studies incorporating advanced MRI and molecular diagnostics may reduce the need for surgical biopsy in equivocal cases. Conclusion These two contrasting cases highlight the critical importance of accurately distinguishing infiltrative spinal cord neoplasms from inflammatory demyelinating conditions. A systematic diagnostic approach that integrates subtle radiological features, targeted serological testing, and histopathological confirmation can prevent unnecessary surgical interventions, reduce morbidity, and ensure timely initiation of appropriate therapy. This comparative analysis underscores the complexity of intramedullary spinal cord lesions and reinforces the necessity of diagnostic vigilance and multidisciplinary collaboration in optimizing patient outcomes. Declarations Acknowledgement We sincerely acknowledge Dr. Abhaya Kumar, whose expert neurosurgical guidance, mentorship, and operative skill were instrumental in the management of these complex intramedullary spinal cord cases and in shaping the clinical insights presented in this manuscript. Consent Consent has been taken from the patients to publish the study References Crawley JN (2020) Intramedullary tumours and tumour mimics. The Royal College of Radiologists . PubMed Saito K, Ohata K, Endoh M et al (2018) Intraoperative frozen-section diagnosis and outcome of intramedullary spinal ependymoma versus astrocytoma. Neurosurgery. ;? (see intraoperative frozen-section study) PubMed Zhu Z et al (2022) Automated Classification of Intramedullary Spinal Cord Tumors and Inflammatory Demyelinating Lesions Using Deep Learning. Radiology . PubMed Sellar R, Hardy K et al (2018) Location, length, and enhancement: systematic approach to differentiating intramedullary spinal cord lesions. Insights Imaging . ;9(6):??? SpringerOpen Weng L et al (2008) Intramedullary non-specific inflammatory lesion of thoracic spine: a case report. World J Surg Oncol 8:3 BioMed Central Parker W et al Neoplastic and paraneoplastic involvement of the spinal cord. Curr Oncol. 2016;? PubMed Rossi A et al (2021) Intramedullary spinal cord metastasis mimicking astrocytoma: case report. Brain Sci . ;11(9):1124. MDPI Payer S, Mende K, Westphal M, Eicker S (2015) Intramedullary spinal cord metastases: an increasingly common diagnosis. Neurosurg Focus 39:E15 PubMed Zhang L, Feng M (2013) Differentiation between intramedullary spinal ependymoma and astrocytoma: comparative MRI analysis. Clin Radiol 68(3):284–290 PubMed Dupont S et al (2022) Intramedullary spinal cord lesions: a single-center experience. J Neurooncol. ;? PubMed StatPearls Intramedullary Spinal Cord Tumors. NCBI Bookshelf . NCBI Woodruff WW Spinal Cord Tumors. In: Holland-Frei Cancer Medicine . 6th ed. NCBI Bookshelf. NCBI Grady C, Melnick K, Porche K et al (2022) Glioma Immunotherapy: Advances and Challenges for Spinal Cord Gliomas. Neurospine 19(1):13–29 e-neurospine.org Brotchi J Intramedullary spinal cord tumors and pseudotumors: how to deal with them. WFNS Clinical Resources. WFNS Neuropathology V – Diseases of Myelin: Neuromyelitis Optica Spectrum Disorder. LWW . LWW CDN Links Consensus-NMOSD EN National Consensus on the Diagnosis of NMOSD and Related Disorders. Nevrologia BG Dahle C et al Review article on spinal cord longitudinally extensive transverse myelitis (LETM) and its mimics. edoc MDC Berlin . MDC Repository Smith MP et al (2016) Balo concentric sclerosis. Lancet Neurology . Wikipedia Chuhutin A, Wlodarczyk A, Jespersen SN, Shemesh N (2018) Diffusion Kurtosis Imaging maps neural damage in the EAE model of MS. bioRxiv/ArXiv. arXiv Duarte TS, Shemesh N (2019) Tract-specific signatures in spinal cord white matter by magnetization-transfer imaging. bioRxiv/ArXiv . arXiv Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8126271","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":545733602,"identity":"30611684-1eca-4284-8d00-169ef61f8057","order_by":0,"name":"Harsh Patel","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAx0lEQVRIiWNgGAWjYBACAwbmgw8SDCTkQJwDD4jTwpZs8KDCxhisJYE4LTxmgg/OpCU2gHhEaTGXbktjSGw7nD4/7PBDoC12croNBLRYzjl87AFQS+7G22kGQC3JxmYHCDnsRlq6AVjL7ASQlgOJ2whryTGTADnMcHb6BxK0JJxJS5CXziHWljvHkg0SKmwMN0jnFBxIMCDGL7ebDz78YSAhLz87ffOHDxV2cgS1MEjA9IJVGhBSjqxFvoEY1aNgFIyCUTAiAQDAzU27VpaInwAAAABJRU5ErkJggg==","orcid":"","institution":"kokilaben dhirubhai ambani hospital \u0026 research institute","correspondingAuthor":true,"prefix":"","firstName":"Harsh","middleName":"","lastName":"Patel","suffix":""},{"id":545733603,"identity":"181068cd-4ad6-4f97-b5e8-b4a496492d19","order_by":1,"name":"Preeti Singh","email":"","orcid":"","institution":"kokilaben dhirubhai ambani hospital \u0026 research institute","correspondingAuthor":false,"prefix":"","firstName":"Preeti","middleName":"","lastName":"Singh","suffix":""},{"id":545733781,"identity":"bf05bba5-6b16-4d66-8ebe-25c144e4972c","order_by":2,"name":"Abhaya Kumar","email":"","orcid":"","institution":"kokilaben dhirubhai ambani hospital \u0026 research institute","correspondingAuthor":false,"prefix":"","firstName":"Abhaya","middleName":"","lastName":"Kumar","suffix":""}],"badges":[],"createdAt":"2025-11-16 09:21:15","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-8126271/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8126271/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":96365920,"identity":"46713a61-4289-4656-9a91-c51ddc5e15e6","added_by":"auto","created_at":"2025-11-20 10:10:57","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":2449190,"visible":true,"origin":"","legend":"","description":"","filename":"infiltrating.docx","url":"https://assets-eu.researchsquare.com/files/rs-8126271/v1/96191c1e183bc894f6bafccb.docx"},{"id":96302783,"identity":"6aad08f2-f51d-493e-967b-da67608bbfb9","added_by":"auto","created_at":"2025-11-19 14:44:32","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":342,"visible":true,"origin":"","legend":"","description":"","filename":"rs8126271.json","url":"https://assets-eu.researchsquare.com/files/rs-8126271/v1/34c65220556b2e32f2393c4b.json"},{"id":96302786,"identity":"a135e37b-5312-4f44-a300-97267f8ff2a0","added_by":"auto","created_at":"2025-11-19 14:44:32","extension":"xml","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":47594,"visible":true,"origin":"","legend":"","description":"","filename":"rs81262710enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-8126271/v1/8195c684e8c2d0d4a88f403d.xml"},{"id":96302790,"identity":"01fc926d-e8bb-4576-ba81-198b89448a1f","added_by":"auto","created_at":"2025-11-19 14:44:32","extension":"png","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":626266,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8126271/v1/5a7c164af0bd0100a8bb2000.png"},{"id":96302800,"identity":"657e64c5-c2b3-4895-a87f-98ee79b95716","added_by":"auto","created_at":"2025-11-19 14:44:32","extension":"png","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":209076,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8126271/v1/6fdcde7a996f0ac703bee6f3.png"},{"id":96302795,"identity":"0feb0367-a894-4578-964f-0c925ea31886","added_by":"auto","created_at":"2025-11-19 14:44:32","extension":"png","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":57215,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-8126271/v1/c58636605f4348df668b6008.png"},{"id":96302797,"identity":"6681700a-af27-4fe9-87d5-8b43da940715","added_by":"auto","created_at":"2025-11-19 14:44:32","extension":"png","order_by":12,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":329038,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-8126271/v1/046db8be9e843bb7ba997923.png"},{"id":96302793,"identity":"e59d74cb-3dc8-43b8-835e-41150742422b","added_by":"auto","created_at":"2025-11-19 14:44:32","extension":"png","order_by":13,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":151657,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-8126271/v1/d5bf212cf9e1cca2d8411c10.png"},{"id":96365574,"identity":"28f122bc-5833-42bc-934b-3badb12b20ac","added_by":"auto","created_at":"2025-11-20 10:10:32","extension":"png","order_by":14,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":291755,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-8126271/v1/82b085a1a4b759d600fc2127.png"},{"id":96302798,"identity":"bdc47727-a227-4ff4-aded-41b4ce8541af","added_by":"auto","created_at":"2025-11-19 14:44:32","extension":"xml","order_by":15,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":45313,"visible":true,"origin":"","legend":"","description":"","filename":"rs81262710structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8126271/v1/8d18a9bd7b6680c8eeaab837.xml"},{"id":96302796,"identity":"d0414956-f41e-45ba-9308-4986c2290548","added_by":"auto","created_at":"2025-11-19 14:44:32","extension":"html","order_by":16,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":53203,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8126271/v1/b0e8f54ed4f3867e728b6413.html"},{"id":96302784,"identity":"35521650-8870-4b68-aff5-f5ac5cdec8c6","added_by":"auto","created_at":"2025-11-19 14:44:32","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":876054,"visible":true,"origin":"","legend":"\u003cp\u003eMRI Cervical Spine showing a long-segment intramedullary T₂ hyperintensity extending from C2 to C5, associated with cord expansion\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8126271/v1/c9bfd4675845838ad4c02a8d.jpeg"},{"id":96363985,"identity":"85cdaf59-022e-40f0-a754-f954f9725771","added_by":"auto","created_at":"2025-11-20 10:08:39","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":762256,"visible":true,"origin":"","legend":"\u003cp\u003ea) Intra operative image before and after tumor removal b)Pre and post operative MRI\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8126271/v1/729a5c2ab47540cd8103d602.jpeg"},{"id":96365738,"identity":"5f105a64-dc87-4d9f-8d36-6be4add9f7d8","added_by":"auto","created_at":"2025-11-20 10:10:44","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":349537,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eHistopathological examination\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-8126271/v1/11d17c05fb4d5945a95e3ef2.png"},{"id":96302787,"identity":"ee30012f-3f28-4395-bf2f-5b2ec9e86a5a","added_by":"auto","created_at":"2025-11-19 14:44:32","extension":"jpeg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":825153,"visible":true,"origin":"","legend":"\u003cp\u003eMRI demonstrated long-segment involvement of the cervicomedullary junction and upper cervical cord, with diffuse holocord swelling and patchy eccentric enhancement. Small intramedullary cysts were noted at the C1–C2 level.\u003c/p\u003e","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8126271/v1/bf0c5b91406e106658e16ac3.jpeg"},{"id":96365712,"identity":"64c63145-1d10-460b-8521-add4ddf8f9bf","added_by":"auto","created_at":"2025-11-20 10:10:43","extension":"jpeg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":77337,"visible":true,"origin":"","legend":"\u003cp\u003eIntraoperative image\u003c/p\u003e","description":"","filename":"floatimage5.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8126271/v1/ccf129be69b12ef0f7fc6b6f.jpeg"},{"id":96365427,"identity":"1f1a3c23-93cd-4dff-be9f-ba8ef8a6f231","added_by":"auto","created_at":"2025-11-20 10:10:21","extension":"jpeg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":192418,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eHistopathological Examination\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage6.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8126271/v1/63a7feded69d903542f9b6e6.jpeg"},{"id":96369329,"identity":"7e36da74-5787-4f01-a555-d784924354c7","added_by":"auto","created_at":"2025-11-20 10:20:31","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3949003,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8126271/v1/4c89e1fa-9a13-484e-80fd-741207f58862.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eInfiltrating Tumor vs Demyelination Disorders: Case Study of Two Adults\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eLong-segment cervical spinal cord lesions frequently blur the diagnostic boundaries between neoplastic and inflammatory etiologies, creating significant challenges for neurosurgeons tasked with determining when surgical intervention is warranted. Infiltrative intramedullary tumors\u0026mdash;particularly astrocytomas\u0026mdash;may closely resemble inflammatory demyelinating disorders such as NMOSD, tumefactive demyelination, or MOG-associated disease. This overlap is compounded by similarities in radiological features, including enhancement patterns, metabolic activity on PET-CT, and varying degrees of cord expansion, any of which may misleadingly suggest a neoplastic process.\u003c/p\u003e\u003cp\u003eSuch ambiguity can result in critical clinical consequences, ranging from unnecessary or overly aggressive surgery in a demyelinating condition to delayed biopsy and tumor treatment when malignancy is present. These two cases highlight the subtle clinical cues, radiological discriminators, and multidisciplinary reasoning essential for navigating this diagnostic grey zone. They underscore the importance of integrating neurosurgical judgment with immunological and radiological expertise to ensure timely, accurate diagnosis and optimal patient outcomes.\u003c/p\u003e"},{"header":"Case 1: High‑Grade Spinal Astrocytoma","content":"\u003cp\u003eA middle-aged female presented with progressively worsening neck pain accompanied by limb weakness and gait imbalance over several weeks. There was no history of trauma, fever, weight loss, or preceding infection to suggest an alternative systemic cause. As her condition evolved, she developed acute urinary retention and constipation, indicating emerging high-grade cervical myelopathy and prompting urgent neurosurgical evaluation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Examination\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOn examination, the patient was alert, oriented, and cooperative. Motor testing revealed asymmetric quadriparesis, with increased tone in the lower limbs and variable tone in the upper limbs. Deep tendon reflexes were brisk throughout, and bilateral extensor plantar responses were elicited. Cranial nerve function remained intact. Overall, the neurological profile was consistent with upper motor neuron involvement localizing to the cervical spinal cord.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLaboratory Investigations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLaboratory evaluation showed hemoglobin of 14.4 g/dL, leukocytosis with a WBC count of 13,600/\u0026micro;L, and normal platelet levels. CRP was mildly elevated at 6.7 mg/L, while liver function tests were within normal limits. Serum total protein was slightly reduced at 5.7 g/dL with an albumin level of 4.05 g/dL. Cerebrospinal fluid analysis revealed 1 WBC/\u0026micro;L, 6 RBCs/\u0026micro;L, elevated protein at 79 mg/dL, and glucose of 66 mg/dL. Serological testing for NMO-IgG, MOG-IgG, and vasculitis markers was negative. Overall, despite comprehensive laboratory, CSF, and serological evaluation, no definitive inflammatory or autoimmune etiology was identified.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRadiological Evaluation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFigure 1: MRI Cervical Spine showing a long-segment intramedullary T₂ hyperintensity extending from C2 to C5, associated with cord expansion\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMRI Spine\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMRI of the cervical spine demonstrated a long-segment intramedullary T₂ hyperintensity extending from C2 to C5, associated with cord expansion and patchy, faint post-contrast enhancement. Additionally, a mild altered signal was noted in the upper thoracic segments (T2\u0026ndash;T4). The radiological impression predominantly favored an inflammatory or immune-mediated demyelinating process; however, the possibility of an infiltrative neoplasm could not be excluded\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePET-CT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePET-CT demonstrated linear increased metabolic activity extending from C2 to C5, corresponding to the region of T₂ hyperintensity on MRI. While this uptake pattern supported active pathology within the cervical cord, it remained nonspecific and did not conclusively distinguish between an inflammatory demyelinating process and an infiltrative neoplasm.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInitial Management\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patient was initiated on high-dose intravenous methylprednisolone for three days; however, her neurological status deteriorated, with new-onset acute urinary retention, constipation, and progressive limb weakness. In view of steroid failure, she subsequently received intravenous immunoglobulin (2 g/kg over five days), but no clinical improvement was observed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNeurosurgical Referral \u0026amp; Decision-Making\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDue to progressive decline despite immunotherapy and the possibility of neoplasm, the patient was referred to neurosurgery.A decision was made to perform \u003cstrong\u003esurgical debulking and biopsy\u003c/strong\u003e of the lesion.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSurgical Intervention\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA \u003cstrong\u003edebulking biopsy\u003c/strong\u003e of the intramedullary lesion was performed.There were no intraoperative complications. The patient was continued on postoperative intravenous steroids.\u003c/p\u003e\n\u003cp\u003eFigure 2 a) Intra operative image before and after tumor removal b)Pre and post operative MRI\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHistopathology Findings\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 3 : Histopathological examination\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHistopathological examination confirmed a WHO Grade III spinal astrocytoma. The lesion demonstrated a hypercellular glial neoplasm with marked nuclear atypia, increased mitotic activity, and an infiltrative growth pattern. Immunohistochemistry showed strong GFAP positivity, supporting its glial origin. These features collectively established the diagnosis of a high-grade infiltrating astrocytoma.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePostoperative Course\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePostoperatively, the patient showed no significant neurological recovery. Instead, she progressed to spastic quadriparesis and remained severely functionally impaired, requiring full assistance for activities of daily living.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFurther Management\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patient subsequently underwent 25 cycles of radiation therapy along with intensive physiotherapy and occupational therapy. She was also initiated on Lokomat-assisted robotic gait training in an effort to optimize functional recovery. A urology consultation was obtained for persistent neurogenic bladder dysfunction, resulting in the placement of a suprapubic cystostomy. Despite comprehensive rehabilitation and multimodal supportive care, her neurological improvement remained minimal, reflecting the aggressive and infiltrative nature of the underlying tumor.\u003c/p\u003e"},{"header":"Case 2: Demyelinating Pseudotumor – Neuromyelitis Optica Spectrum Disorder (NMOSD)","content":"\u003cp\u003eA 47-year-old male presented with sudden-onset weakness of the right lower limb, which progressed to involve the right upper limb over a 15-day period. The deficits evolved steadily without any preceding trauma, fever, constitutional symptoms, or visual disturbances to suggest optic neuritis or other systemic involvement.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Examination\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOn examination, the patient was conscious, oriented, and hemodynamically stable, with intact cranial nerve function. Motor testing revealed asymmetric weakness, with power of 3/5 in the right upper limb and 4/5 in the right lower limb, accompanied by reduced tone on the right side. Deep tendon reflexes were exaggerated on the right, including the biceps, triceps, supinator, knee, and ankle jerks. Mild upper cervical tenderness was noted at the C1\u0026ndash;C2 level. Sensory examination showed no clear modality dissociation, and bowel and bladder functions were preserved at the time of presentation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRadiological Evaluation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMRI Cervical Spine\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFigure 4: MRI demonstrated long-segment involvement of the cervicomedullary junction and upper cervical cord, with diffuse holocord swelling and patchy eccentric enhancement. Small intramedullary cysts were noted at the C1\u0026ndash;C2 level.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe overall radiological appearance strongly suggested an infiltrative intramedullary neoplasm, particularly an astrocytoma or ependymoma. However, PET-CT revealed no corresponding metabolically active lesion, creating a notable discordance between structural and metabolic imaging and raising uncertainty regarding the underlying pathology.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInitial Management\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patient was treated with high-dose intravenous methylprednisolone; however, no meaningful clinical improvement was observed. In view of the persistent deficits and MRI findings highly suggestive of an intramedullary neoplasm, a surgical biopsy was undertaken to establish a definitive diagnosis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSurgical Intervention\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA \u003cstrong\u003etotal C3\u0026ndash;C4 laminectomy\u003c/strong\u003e with biopsy of the intramedullary lesion was performed under intraoperative neuromonitoring (IONM). No gross tumor mass was visualized intraoperatively.\u003c/p\u003e\n\u003cp\u003eFigure 5 : Intraoperative image\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePost-operative Course\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePostoperatively, the patient developed recurrent paroxysmal dystonic episodes involving the face and right-sided limbs, each lasting 5\u0026ndash;6 seconds. These events increased progressively in frequency and were accompanied by worsening right hemiparesis, marking a significant deterioration in his neurological status.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHistopathological Findings\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInitial histopathological evaluation suggested a demyelinating pseudotumor characterized by reactive gliosis, without definitive neoplastic cells. Certain features resembled therapy-related changes sometimes seen in lymphomas following corticosteroid exposure, contributing to diagnostic ambiguity. A subsequent expert review, however, confirmed a non-neoplastic inflammatory demyelinating process, with no evidence of astrocytoma, lymphoma, or ependymoma, thereby establishing the diagnosis of an inflammatory demyelinating lesion rather than an infiltrative tumor.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 6: Histopathological Examination\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFurther Diagnostic Testing\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA neurology consultation was sought, and serological testing revealed a positive serum NMO-IgG (AQP4 antibody), while the ANA profile and ACE levels were within normal limits. Although the patient exhibited no clinically overt optic neuritis, the presence of longitudinally extensive transverse myelitis together with NMO antibody positivity established the diagnosis of neuromyelitis optica spectrum disorder (NMOSD) presenting as a demyelinating pseudotumor.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDefinitive Management\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patient was managed with continuation of intravenous corticosteroids, followed by five cycles of plasmapheresis in view of persistent neurological deficits. He concurrently underwent intensive physiotherapy and occupational therapy to address functional decline. During follow-up, rituximab immunotherapy was initiated as long-term disease-modifying treatment for NMOSD.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOutcome\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patient remained stable and demonstrated \u003cstrong\u003epartial neurological recovery\u003c/strong\u003e, with reduction in dystonic episodes and improved right-sided motor function over subsequent weeks. At follow-up, he achieved meaningful functional gains with continued rehabilitation and immunotherapy.\u003c/p\u003e\n\u003ch2\u003eComparative Discussion\u003c/h2\u003e\n\u003cp\u003eBoth cases initially exhibited overlapping radiological features, including long-segment T2 hyperintensity, cord expansion, and patchy enhancement, making early differentiation challenging. However, several discriminative clues emerged during evaluation. Demyelinating lesions characteristically demonstrate open-ring or incomplete enhancement patterns, whereas neoplastic lesions more often present with closed, nodular, or homogeneous enhancement. PET-CT, although useful, may be misleading, as inflammatory activity can mimic hypermetabolism typically associated with tumors. Clinical trajectories also diverge: infiltrative tumors tend to show relentless neurological deterioration, whereas inflammatory lesions may fluctuate or show partial response to immunotherapy. Ultimately, when imaging and clinical features remain ambiguous, histopathological examination remains the most reliable method for establishing a definitive diagnosis.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eLong-segment intramedullary spinal cord lesions, especially those involving the cervical region, remain a profound diagnostic challenge. As illustrated by our two cases, the differential diagnosis frequently includes both neoplastic processes (such as astrocytoma or ependymoma) and inflammatory demyelinating disorders (such as NMOSD). The implications of misdiagnosis are substantial, given that therapeutic strategies diverge sharply: neoplasms often require surgical intervention, whereas demyelinating lesions generally respond to immunotherapy [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e\u003cdiv id=\"Sec27\" class=\"Section2\"\u003e\u003ch2\u003eRadiological Features and Diagnostic Pitfalls\u003c/h2\u003e\u003cp\u003eMagnetic resonance imaging (MRI) is the cornerstone of evaluation for intramedullary spinal cord lesions. However, despite its sensitivity, MRI lacks absolute specificity. Astrocytomas and ependymomas can both present as long-segment T2-hyperintense lesions with cord expansion and contrast enhancement, overlapping significantly with inflammatory etiologies [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Distinguishing features on MRI have been described: ependymomas often exhibit a \u0026ldquo;cap sign,\u0026rdquo; central location, syringohydromyelia, and diffuse enhancement, whereas astrocytomas may show eccentric location, heterogeneous enhancement, and satellite cysts [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eEnhancement patterns also yield important clues: inflammatory demyelination more often demonstrates open-ring or incomplete-ring enhancement, whereas neoplastic lesions frequently show closed, nodular, or solid enhancement [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The \u0026ldquo;lens-shaped\u0026rdquo; enhancement on sagittal sequences has even been reported in NMOSD in some cases [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Nevertheless, reliance on MRI alone can mislead: pseudotumoral demyelination may mimic tumoral growth, and surgical intervention based solely on imaging may be fraught with risk [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e\u003cp\u003ePET-CT, while increasingly used as an adjunct, may also mislead. Inflammatory lesions can show metabolic activity, resulting in false positives for neoplastic disease [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Emerging tools like deep learning-based MRI segmentation and classification have shown promise in differentiating tumors from demyelination; for example, a recent model achieved high accuracy in distinguishing astrocytoma vs. NMOSD vs. ependymoma using T2-weighted MRI [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Nonetheless, these remain investigational and cannot yet replace histological diagnosis in ambiguous cases.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec28\" class=\"Section2\"\u003e\u003ch2\u003eRole of Serology and Clinical Correlation\u003c/h2\u003e\u003cp\u003eThe clinical trajectory and serological markers provide additional, often decisive, information. NMOSD is strongly associated with aquaporin-4 (AQP4) antibodies, and longitudinally extensive transverse myelitis (LETM) involving\u0026thinsp;\u0026ge;\u0026thinsp;3 vertebral segments is a hallmark [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. However, lesion length alone is insufficient to confirm NMOSD: various pathological processes\u0026mdash;including neoplasia, sarcoidosis, and vascular lesions\u0026mdash;can produce LETM-like MRI appearances [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Positive AQP4 serology in the absence of optic neuritis has been well described, and a diagnosis of NMOSD may be established based on MRI and serology even without optic nerve involvement, as in our second case [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eConversely, neoplastic lesions typically follow a more insidious but relentless clinical decline, though exceptions exist. Paraneoplastic processes and metastases (though rare) must also be kept in mind, especially in patients without typical demyelinating features [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Indeed, intramedullary spinal cord metastases (ISCM) are rare but increasingly reported; newer case reports have documented lesions mimicking astrocytoma on imaging but later proven to be metastatic carcinoma [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec29\" class=\"Section2\"\u003e\u003ch2\u003eHistopathological Confirmation\u003c/h2\u003e\u003cp\u003eGiven the overlapping clinical and imaging features, histopathology frequently remains the definitive arbiter. Intraoperative frozen-section diagnosis is commonly used but less reliable in spinal cord tumors compared to intracranial ones; accuracy for ependymoma vs. astrocytoma can be as low as ~\u0026thinsp;70% [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Moreover, technique and sample adequacy strongly influence the result. The neurosurgical decision-making process, therefore, must factor in not only imaging and intraoperative findings but also the surgeon\u0026rsquo;s judgment about the risks and benefits of biopsy versus resection [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eTherapeutic Implications and Outcomes\u003c/h3\u003e\n\u003cp\u003eManagement strategies diverge markedly upon diagnosis. For primary intramedullary tumors such as ependymoma, gross total resection (GTR) can often be achieved, and is associated with better outcomes [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In contrast, astrocytomas, especially high-grade, are more infiltrative and less amenable to complete resection, and the extent of resection may not correlate well with survival [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. For inflammatory demyelinating lesions like NMOSD, high-dose steroids, plasmapheresis, and long-term immunotherapy (e.g., rituximab) are the mainstays [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Early initiation of therapy can arrest or even reverse clinical decline if correctly diagnosed.\u003c/p\u003e\u003cdiv id=\"Sec31\" class=\"Section2\"\u003e\u003ch2\u003eMultidisciplinary Approach and Emerging Directions\u003c/h2\u003e\u003cp\u003eThese cases highlight the essential need for a multidisciplinary team (neurosurgeons, neurologists, radiologists, pathologists) in the evaluation of ambiguous intramedullary lesions. Clinical history, radiology, serology, intraoperative findings, and pathology must be concordant, and discrepancies should prompt reconsideration rather than premature intervention [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eEmerging modalities may further aid diagnosis. Deep learning-based image analysis has shown strong performance in lesion classification [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Advanced MRI techniques\u0026mdash;such as diffusion kurtosis imaging (DKI) and magnetization-transfer imaging\u0026mdash;also provide microstructural insights into tissue integrity and myelin status, potentially offering non-invasive biomarkers of demyelination versus neoplasia [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Finally, immunotherapy for spinal cord gliomas (e.g., glioma immunotherapy) is being explored, though challenges remain due to the blood\u0026ndash;spinal cord barrier and tumor heterogeneity [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec32\" class=\"Section2\"\u003e\u003ch2\u003eLimitations and Future Considerations\u003c/h2\u003e\u003cp\u003eOur report is limited by its small sample size (two cases) and retrospective nature. While we provide a detailed narrative, the generalizability is constrained. Larger studies or registries are needed to better characterize imaging features, clinical trajectories, and outcomes of tumor vs. pseudotumor in intramedullary spinal disease. Furthermore, prospective studies incorporating advanced MRI and molecular diagnostics may reduce the need for surgical biopsy in equivocal cases.\u003c/p\u003e\u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThese two contrasting cases highlight the critical importance of accurately distinguishing infiltrative spinal cord neoplasms from inflammatory demyelinating conditions. A systematic diagnostic approach that integrates subtle radiological features, targeted serological testing, and histopathological confirmation can prevent unnecessary surgical interventions, reduce morbidity, and ensure timely initiation of appropriate therapy. This comparative analysis underscores the complexity of intramedullary spinal cord lesions and reinforces the necessity of diagnostic vigilance and multidisciplinary collaboration in optimizing patient outcomes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe sincerely acknowledge Dr. Abhaya Kumar, whose expert neurosurgical guidance, mentorship, and operative skill were instrumental in the management of these complex intramedullary spinal cord cases and in shaping the clinical insights presented in this manuscript.\u003c/p\u003e\u003cp\u003eConsent\u003c/p\u003e\u003cp\u003eConsent has been taken from the patients to publish the study\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCrawley JN (2020) Intramedullary tumours and tumour mimics. \u003cem\u003eThe Royal College of Radiologists\u003c/em\u003e. PubMed\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSaito K, Ohata K, Endoh M et al (2018) Intraoperative frozen-section diagnosis and outcome of intramedullary spinal ependymoma versus astrocytoma. Neurosurgery. ;? (see intraoperative frozen-section study) PubMed\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhu Z et al (2022) Automated Classification of Intramedullary Spinal Cord Tumors and Inflammatory Demyelinating Lesions Using Deep Learning. \u003cem\u003eRadiology\u003c/em\u003e. PubMed\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSellar R, Hardy K et al (2018) Location, length, and enhancement: systematic approach to differentiating intramedullary spinal cord lesions. \u003cem\u003eInsights Imaging\u003c/em\u003e. ;9(6):??? SpringerOpen\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWeng L et al (2008) Intramedullary non-specific inflammatory lesion of thoracic spine: a case report. World J Surg Oncol 8:3 BioMed Central\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eParker W et al Neoplastic and paraneoplastic involvement of the spinal cord. Curr Oncol. 2016;? PubMed\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRossi A et al (2021) Intramedullary spinal cord metastasis mimicking astrocytoma: case report. \u003cem\u003eBrain Sci\u003c/em\u003e. ;11(9):1124. MDPI\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePayer S, Mende K, Westphal M, Eicker S (2015) Intramedullary spinal cord metastases: an increasingly common diagnosis. Neurosurg Focus 39:E15 PubMed\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhang L, Feng M (2013) Differentiation between intramedullary spinal ependymoma and astrocytoma: comparative MRI analysis. Clin Radiol 68(3):284\u0026ndash;290 PubMed\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDupont S et al (2022) Intramedullary spinal cord lesions: a single-center experience. J Neurooncol. ;? PubMed\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eStatPearls Intramedullary Spinal Cord Tumors. \u003cem\u003eNCBI Bookshelf\u003c/em\u003e. NCBI\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWoodruff WW Spinal Cord Tumors. In: \u003cem\u003eHolland-Frei Cancer Medicine\u003c/em\u003e. 6th ed. NCBI Bookshelf. NCBI\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGrady C, Melnick K, Porche K et al (2022) Glioma Immunotherapy: Advances and Challenges for Spinal Cord Gliomas. Neurospine 19(1):13\u0026ndash;29 e-neurospine.org\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBrotchi J Intramedullary spinal cord tumors and pseudotumors: how to deal with them. WFNS Clinical Resources. WFNS\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNeuropathology V \u0026ndash; Diseases of Myelin: Neuromyelitis Optica Spectrum Disorder. \u003cem\u003eLWW\u003c/em\u003e. LWW CDN Links\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eConsensus-NMOSD EN National Consensus on the Diagnosis of NMOSD and Related Disorders. Nevrologia BG\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDahle C et al Review article on spinal cord longitudinally extensive transverse myelitis (LETM) and its mimics. \u003cem\u003eedoc MDC Berlin\u003c/em\u003e. MDC Repository\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSmith MP et al (2016) Balo concentric sclerosis. \u003cem\u003eLancet Neurology\u003c/em\u003e. Wikipedia\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChuhutin A, Wlodarczyk A, Jespersen SN, Shemesh N (2018) Diffusion Kurtosis Imaging maps neural damage in the EAE model of MS. bioRxiv/ArXiv. arXiv\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDuarte TS, Shemesh N (2019) Tract-specific signatures in spinal cord white matter by magnetization-transfer imaging. \u003cem\u003ebioRxiv/ArXiv\u003c/em\u003e. arXiv\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Kokilaben Dhirubhai Ambani Hospital","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":"infiltrating, demyelination, tumor, NMOSD, intramedullary , astrocytoma","lastPublishedDoi":"10.21203/rs.3.rs-8126271/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8126271/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eLong-segment intramedullary spinal cord lesions pose a unique diagnostic and therapeutic dilemma from a neurosurgical perspective. For the operating surgeon, the central challenge lies in distinguishing infiltrative intramedullary tumors from inflammatory demyelinating pathologies, as both may mimic each other clinically and radiologically. This distinction is critical: while early biopsy or decompressive surgery may be warranted for progressive neoplasms, unnecessary intervention in demyelinating disorders can result in avoidable morbidity in an already high-risk spinal cord environment.\u003c/p\u003e\u003cp\u003eThis report details two diagnostically challenging adult cases encountered in neurosurgical practice\u0026mdash;one ultimately proven to be a Grade III spinal astrocytoma requiring definitive surgical management, and the other a neuromyelitis optica spectrum disorder (NMOSD) masquerading as a spinal cord tumor. By comparing their clinical progression, operative considerations, intraoperative neurophysiology, radiological subtleties, and final diagnoses, we highlight key decision points that influence whether to operate, observe, or pursue advanced immunologic testing. The aim is to provide neurosurgeons with a practical reference when faced with similar long-segment intramedullary lesions, underscoring the profound impact that early diagnostic accuracy has on surgical planning, neurological outcomes, and long-term patient quality of life.\u003c/p\u003e","manuscriptTitle":"Infiltrating Tumor vs Demyelination Disorders: Case Study of Two Adults","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-19 14:44:27","doi":"10.21203/rs.3.rs-8126271/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e7489163-cea3-4395-9506-501e40e95e88","owner":[],"postedDate":"November 19th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":58059843,"name":"Neurosurgery"}],"tags":[],"updatedAt":"2025-11-19T14:44:27+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-19 14:44:27","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8126271","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8126271","identity":"rs-8126271","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}