Unraveling the Complexity of Area Postrema Lesions: Insights from Neuromyelitis Optica Spectrum Disorder and Beyond

Unraveling the Complexity of Area Postrema Lesions: Insights from Neuromyelitis Optica Spectrum Disorder and Beyond | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Unraveling the Complexity of Area Postrema Lesions: Insights from Neuromyelitis Optica Spectrum Disorder and Beyond Jing Li, yan yang, ya Hu, xiangdong Jia, junling ge, guoen yao This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4225506/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 Lesions in the area postrema may lead to symptoms including hiccupping, nausea, and vomiting. Often termed area postrema syndrome, these symptoms are commonly linked to neuromyelitis optica spectrum disorders (NMOSD). This study analyzes two case studies to illustrate the varied clinical manifestations of area postrema lesions. The first case involves a 57-year-old male presenting with persistent symptoms of nausea, vomiting, and dizziness. Subsequent examination led to a diagnosis of WHO Grade II astrocytoma. The second case details a 24-year-old woman with hiccupping, deteriorating vision, incontinence, and limb numbness. She was subsequently diagnosed with concurrent neuromyelitis optica spectrum disorder (NMOSD) and Sjögren's syndrome. Importantly, the second case showed distinct gastrointestinal symptoms before treatment, leading to a crucial diagnosis of lesions in the posterior medullary region. These case studies highlight the risk of misdiagnosis and underscore the importance of quickly recognizing posterior medulla-related symptoms. A deep understanding of postrema lesions is essential for accurate diagnosis and prompt management. This underscores the need for a comprehensive clinical approach to enhance patient outcomes. area postrema area postrema syndrome Neuromyelitisoptica spectrumdisorders WHO Grade II Astrocytoma Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction The area postrema, located at the caudal end of the fourth ventricle within the medulla oblongata, is a bilaterally symmetrical structure reminiscent of a leaf. Situated above the vagal triangle, it shares a close association with the nucleus tractus solitarius [ 1 – 2 ] . Characterized by its highly vascular and loosely arranged tissue, the area postrema is notable for its absence of the blood-brain barrier. This feature renders it a critical sensor for hydrophilic compounds that struggle to permeate the blood-brain barrier to access the cerebrospinal fluid (CSF) [ 1 ] . Together with the nucleus of the solitary tract and the dorsal motor nucleus of the vagus nerve, it constitutes the Dorsal Vagal Complex (DVC) [ 2 ] . The DVC plays a pivotal role in managing nausea, vomiting, and hiccupping, in addition to its involvement in eating, metabolism, cardiovascular regulation, and the equilibrium of fluid and CSF [ 1 – 2 ] . Area Postrema Syndrome (APS) manifests through persistent, challenging-to-manage symptoms of nausea, retching, and vomiting persisting for a minimum of 48 hours. APS can present in various forms, including acute, subacute, periodic, or chronic. A definitive diagnosis necessitates the exclusion of other possible causes. Notably, APS may signal the presence of neuromyelitis optica spectrum disorders (NMOSD) due to neuroinflammatory processes within this region [ 2 ] . While APS may arise from non-demyelinating lesions, its association with NMOSD is critical for accurate diagnosis and prognosis, often indicating a more adverse outcome for individuals with NMOSD [ 2 ] . The clinical presentation of APS, chiefly distinguished by relentless and difficult-to-manage nausea and vomiting, complicates diagnosis due to their resemblance to symptoms of gastrointestinal, metabolic, biochemical, and psychiatric conditions [ 3 ] . Consequently, patients with APS frequently encounter a broad spectrum of medical specialties beyond neurology [ 5 ] . Delays in recognizing APS-NMOSD can lead to dire outcomes, including acute myelitis, optic neuritis, or brainstem lesions, potentially resulting in permanent neurological deficits [ 3 ] . In extreme cases, it may precipitate respiratory failure and sudden cardiac arrest, occasionally without prior warning [ 3 ] . The complex nature and varied presentations of APS underscore the necessity for its swift identification and the implementation of effective treatment strategies. This study delves into two particular cases of APS, one associated with NMOSD and the other with medullary astrocytoma. These cases contribute valuable insights into the pathophysiological mechanisms and clinical manifestations of APS, highlighting the critical need for prompt and accurate diagnosis. CASE REPORT CASE 1 A 57-year-old male was admitted to the hospital following the sudden and prolonged emergence of nausea and vomiting, which had persisted for three months. Additionally, he reported experiencing dizziness over the last two weeks. Before hospitalization, the patient had suffered from nausea, vomiting, hiccups, and exacerbated hypertension upon standing. Gastric endoscopy uncovered superficial gastritis and cholecystitis. The patient's symptoms showed limited response to oral interventions, including antihypertensive medications that managed the hypotension effectively but failed to significantly alleviate the gastrointestinal distress. The patient also described feelings of instability while standing and intermittent episodes of lightheadedness. Diagnostic imaging via a head MRI revealed an anomalous mass in the dorsal medulla oblongata. Physical examination indicated asymmetry in the uvula's size and shape, with a pronounced shift to the left. Furthermore, muscle mass loss was noted on the left side of the tongue, causing the tongue to deviate leftward. No signs of meningeal engagement were present. The mass was diagnosed as a WHO Grade II astrocytoma, characterized in MRI scans as a slightly elongated, well-demarcated lesion in the posterior medullary region. The lesion exhibited uniform enhancement, discernible in both T1 and T2 weighted images. Measuring 1.2 cm, the lesion compressed the central canal of the fourth ventricle without displaying abnormal enhancement post-Gd-DTPA injection (refer to Fig. 1 ). Pathological examination confirmed the diagnosis of Grade II astrocytoma (refer to Figs. 2 and 3 ). CASE 2 A 24-year-old woman was admitted to our hospital with a 20-month history of daily hiccups and vomiting. Gastroscopy identified chronic non-atrophic gastritis, yet treatments failed to alleviate her symptoms. Approximately 18 months prior to this visit, she began experiencing a decline in vision. Diagnostic evaluations revealed positivity for AQP-4 antibodies and negativity for MOG antibodies, along with anti-SSB, anti-SSA/60KD, and anti-SSA/52KD antibodies, indicating Sjögren's syndrome. An initial head MRI detected posterior cerebral lesions. Treatment with pulse therapy, comprising methylprednisolone, azathioprine, and cyclophosphamide, led to symptom alleviation. However, ten days before her current admission, the patient developed new symptoms: fecal incontinence, coughing and choking while drinking water, and numbness and weakness in her limbs. These symptoms emerged after she had discontinued her medication two months earlier. A follow-up cranial MRI reconfirmed lesions in the brain's posterior region, and similar pulse therapy yielded symptom improvement. The onset of these symptoms followed a period during which she had ceased her medication, leading to generalized itching, continuous hiccups, reduced appetite, constipation, urination difficulties, abdominal bloating, and coughing upon liquid intake, along with numbness and thermal sensation loss in her limbs. The patient's personal, marital, and family medical histories were unremarkable. Neurological examination at admission showed decreased visual acuity in both eyes, a delayed pharyngeal reflex, reduced muscle strength in all limbs, sensory impairments below the T4 level, and left-sided pathological signs. Extensive MRI imaging of the head and neck revealed abnormal posterior brain signals and segmental demyelination in the cervical cord (refer to Fig. 4 ). The patient underwent pulse therapy with steroids and azathioprine, alongside symptomatic care including enemas and interventions to aid bowel movement, resulting in gradual symptom improvement. Discussion The area postrema, a region within the brain characterized by its high vascularization, features sinusoidal capillaries with pores alongside diverse cell types, including ependymal cells, glial cells, and small neurons. This region stands out from adjacent white matter areas due to its increased surface area, elevated plasma flow, and enhanced permeability [ 2 , 6 ] . The reduced velocity of blood flow facilitates extended transport times for blood-borne signaling molecules and toxins, thereby amplifying the exposure of local neurons and glial cells to blood-derived components. Such characteristics afford the area postrema a significant role in receptor-mediated interactions, essential for internal homeostasis and fluid regulation [ 6 ] . Despite its crucial functions, the diminutive and intricate structure of the area postrema complicates research efforts, prompting continued discourse regarding its exact roles [ 1 , 7 ] . Lesions within this area commonly manifest as persistent nausea, vomiting, and hiccupping [ 8 ] . NMOSD and APS Neuromyelitis Optica Spectrum Disorder (NMOSD) is defined by inflammation and degradation of the myelin sheath enveloping nerve fibers in the central nervous system. It is noteworthy that Area Postrema Syndrome (APS) constitutes one of the six principal symptoms indicative of NMOSD [ 9 ] . NMOSD's development is linked to the presence of autoantibodies targeting aquaporin-4 (AQP4), which can penetrate the blood-brain barrier and instigate astrocyte destruction via complement system activation [ 10 ] . Given the abundant distribution of AQP4 throughout the nervous system, especially in the area postrema, this region is particularly vulnerable to NMOSD [ 5 ] . The prevalence of isolated APS among NMOSD patients ranges from 7.1–10.3%. Conversely, APS presenting alongside other neurological manifestations is reported in 9.4–15.9% of cases, underscoring its rarity as a disease manifestation [ 11 ] . Typically, patients display one to three symptoms, with vomiting being the most common, followed by hiccupping [ 8 , 12 ] . Nausea usually emerges abruptly, vomiting may be sporadic or persistent, often triggered by ingestion, and hiccupping tends to be protracted [ 8 ] . The clinical trajectory of APS varies, with nausea enduring for a median of 14 days, vomiting averaging five episodes per day, and hiccupping lasting a median of 14 days [ 11 ] . These symptoms frequently precede optic neuritis or transverse myelitis, marking early indications of NMOSD [ 3 ] . In our second case, the patient reported enduring, episodic hiccupping and vomiting over two months, showing improvement post steroid and gamma-globulin therapy administration. Nonetheless, detailed data on the specific characteristics and frequency of these episodes remain scarce, largely due to the difficulty patients and their families face in accurately recalling them. Pathologically, NMOSD-associated posterior lesions are characterized by disorganized tissue, thickened vascular walls, and infiltration by activated immune cells, leading to glial cell destruction and neuronal activation, manifesting as nausea and vomiting [6]. The potential reversibility of posterior lesions in NMOSD hints at the transient impairment of astrocyte function [6]. In our second case, the patient presented with persistent posterior medullary lesions on imaging during their hospital stay, suggesting either the partial persistence of the initial lesion, resulting in ongoing damage, or the development of new lesions, as evidenced by the reappearance of posterior medullary symptoms on the second visit. Consequently, while NMOSD lesions may exhibit a degree of reversibility, some residual damage may persist, indicating a partial reversibility of NMOSD-associated posterior lesions. Distinguishing Astrocytoma from NMOSD in APS Patients Astrocytoma is characterized by an aberrant proliferation of glial cells within the area postrema, where these cells multiply more rapidly than normal, often portending a poor prognosis for the patient. Conversely, neuromyelitis optica spectrum disorder (NMOSD) stems from an autoimmune dysfunction, generally presenting a more favorable prognosis than tumors. This distinction underscores the necessity of considering rare tumor disorders in the differential diagnosis of area postrema lesions. Furthermore, NMOSD frequently coexists with other autoimmune disorders, as illustrated in our second case, including Sjögren's syndrome, and may be associated with conditions such as rheumatoid arthritis, systemic lupus erythematosus, antiphospholipid syndrome, and autoimmune thyroid disease (AITD), affecting multiple body systems beyond the neurological sphere [ 13 ] . Imaging distinctions reveal that NMOSD lesions typically exhibit clearer demarcations compared to tumor lesions. NMOSD can impact various brain regions, manifesting as patchy lesions adjacent to the ventricles, the corpus callosum, along the corticospinal tract, within the deep white matter, or as subcortical lesions [ 14 ] . NMOSD is characterized by subtle blood-brain barrier alterations leading to meningeal enhancement and is marked by linear ependymal surface enhancement, akin to pencil-like lesions [ 14 ] . The “linear stripe sign” in sagittal MRI and the “inverted V sign” in horizontal T2 FLAIR sequences are highly specific for APS in NMOSD patients, although these imaging findings may also occur in other conditions [ 5 ] . Astrocytomas present on imaging as irregular masses with vague boundaries, displaying isointense or hypointense signals on T1-weighted images and hyperintense signals on T2-weighted scans. These tumors may present as mixed, cystic, or solid masses, showing localized and irregular enhancement, particularly at the edges, upon Gd-DTPA-enhanced MRI [ 15 ] . In our first case, the tumor manifested as a discrete mass with slight irregular contrast enhancement on enhanced brain MRI, aligning with prior documentation. Unlike systemic tumors, area postrema tumors typically remain localized. Patients with NMOSD may initially exhibit symptoms indicative of antiphospholipid syndrome (APS), emphasizing the importance of conducting additional diagnostic tests, such as serum aquaporin-4 (AQP-4) and myelin oligodendrocyte glycoprotein (MOG) measurements, to differentiate between these conditions. Treatment modalities vary significantly between conditions. For astrocytomas, treatment may involve surgical excision and chemotherapy, tailored to individual tumor characteristics, as demonstrated in our first case, which resulted in a positive outcome post-surgery. NMOSD management includes a regimen of steroids, intravenous immunoglobulin, monoclonal antibodies, immunosuppressants, and symptomatic treatments, targeting the specific needs of various NMOSD presentations. Other Causes of APS Area Postrema Syndrome (APS) can result from autoimmune inflammatory conditions or various tumors located in the area postrema, such as neurocutaneous melanosis, choroid plexus tumors, pilocytic astrocytoma, or neuroenteric cysts [ 4 ] . The first case presented in this study is an example of a WHO Grade II pilocytic astrocytoma, a relatively rare occurrence. Additionally, APS may manifest as an initial symptom of other diseases, including lupus-related neuropathy, CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids), anti-GFAP encephalomyelitis, brainstem encephalitis, and secondary infectious myelitis, though it is uncommon in patients with multiple sclerosis or strokes [ 4 ] . APS is associated with a wide array of conditions ranging from autoimmune and inflammatory disorders to sudden infant death syndrome, Alexander disease, and radiation-induced nausea and vomiting, thereby broadening the spectrum of APS-related conditions [ 3 , 16 ] . Neurologists face the critical task of distinguishing APS from Wernicke's encephalopathy during diagnosis. Despite the differences in etiology and treatment approaches, both conditions may present with similar features, including the affected brain regions, tissue structural changes, and clinical manifestations [ 3 ] . A thorough evaluation is essential for the precise diagnosis and effective management of these conditions, underscoring the complexity and varied nature of APS and highlighting the need for a comprehensive understanding of its potential causes. Clinical Diagnosis Suggestions and Recommendations for Cases Lesions in the postrema region can manifest alongside various neurological symptoms, underscoring the need for an exhaustive neurological evaluation. Persistent symptoms such as prolonged nausea, vomiting, and hiccupping, despite targeted treatment, may indicate the presence of region postrema lesions. Beyond the commonly diagnosed Neuromyelitis Optica Spectrum Disorder (NMOSD), healthcare providers should consider a wide array of potential causes for these lesions. The tumor in our first case is particularly notable for its unusual location, even though the tumor type is relatively common. Regrettably, the tumor sample from the first patient was inadequate for comprehensive genetic analysis, limiting the examination to gross pathology and immunohistochemical studies. Initially, the cases discussed presented with gastrointestinal symptoms, leading patients to seek care from gastroenterology specialists. This approach underscores the critical role of extensive diagnostic evaluations, including upper endoscopy, transit tests, and abdominal CT scans, for patients presenting with these symptoms. However, the emergence of additional neurological symptoms suggesting area postrema involvement often results in diagnostic and treatment delays [ 8 ] . This situation reinforces a key recommendation: medical professionals encountering patients with gastrointestinal complaints, especially nausea, vomiting, and hiccupping, should consider the potential for underlying neurological conditions. Employing a comprehensive diagnostic approach is essential in clinical practice to enhance cause identification, accelerate the diagnostic process, and ensure the provision of timely and appropriate treatment. Prompt assessment of neurological issues enables physicians to more effectively direct further examinations and treatments, laying the foundation for comprehensive and individualized healthcare delivery. Conclusion Our investigation into the area postrema, particularly within the scope of neuromyelitis optica spectrum disease (NMOSD), underscores the critical need for heightened physician awareness regarding these conditions. Symptoms of area postrema syndrome, notably hiccups, nausea, and vomiting, are distinctive yet challenging to diagnose due to their similarity to gastrointestinal disorders. Through detailed examination of two cases, this study illuminates the varied etiologies affecting the posterior medullary region. The first case, involving a WHO Grade II astrocytoma, underlines the potential for tumor-induced symptoms to mimic those of gastrointestinal illnesses, accentuating the necessity for accurate diagnostic techniques. Conversely, the second case elucidates the intricate symptomatology associated with NMOSD, further complicated by concurrent Sjögren's syndrome, demanding an exhaustive and multidisciplinary diagnostic approach. These instances stress the imperative for medical professionals to consider a broad spectrum of differential diagnoses upon encountering symptoms indicative of area postrema involvement, mindful of the overlap between neurological and gastrointestinal manifestations. The high risk of misdiagnosis mandates a detailed and thorough evaluation of the posterior medullary region's anatomy and pathology. Integrating these insights into standard clinical practice is vital to averting diagnostic delays and ensuring the prompt delivery of appropriate treatments. The complex interplay between neurological and gastrointestinal symptoms in the posterior medullary region necessitates a more discerning and nuanced approach to diagnosis, ultimately enhancing care quality for individuals with area postrema syndrome in the context of NMOSD. Declarations Ethical Approval This study was approved by the institutional review board of The Fourth Medical Center of PLA General Hospital, following the principles outlined in the Declaration of Helsinki. The committee stressed the importance of obtaining participants' consent, informed consent, and consent for publication. Author Contributions JL, JLG, and GEY contributed to the conception of the study and clinical image analysis. JL and XDJ were involved in MR data acquisition. JL and YH handled clinical data acquisition. JL and YY are responsible for collecting pathology images. JL, JLG, and GEY contributed to interpretation and drafting, while JLG and GEY played crucial roles in revising for important intellectual content. Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest concerning the research, authorship, and/or publication of this article. Funding The author(s) received no financial support for the research, authorship, and/or publication of this article. Availability of Data and Materials In alignment with the principles of transparency and scientific openness, all pertinent data and materials supporting the findings of this clinical case report are available upon reasonable request. Requests for data should be directed to Jing Li at [email protected] . References Zhang, C., Kaye, J. A., Cai, Z., et al. (2021). Area Postrema Cell Types that Mediate Nausea-Associated Behaviors. Neuron, 109(3), 461–472.e5. https://doi.org/10.1016/j.neuron.2020.11.010 Mirza, M., & Das, J. M. (2023, August 8). Neuroanatomy, Area Postrema. In StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. PMID: 31334969. Zhou, C., Liao, L., Sun, R., et al. (2021). Area postrema syndrome as initial manifestation in neuromyelitis optica spectrum disorder patients: A retrospective study. 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(2018, October 23). Area postrema syndrome: Frequency, criteria, and severity in AQP4-IgG-positive NMOSD. Neurology, 91(17), e1642-e1651. https://doi.org/10.1212/WNL.0000000000006392 Wingerchuk, D. M., Banwell, B., Bennett, J. L., et al. (2015). International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology, 85, 177–189. https://doi.org/10.1212/WNL.0000000000001729 Huda, S., Whittam, D., Bhojak, M., et al. (2019, March). Neuromyelitis optica spectrum disorders. Clin Med (Lond), 19(2), 169–176. https://doi.org/10.7861/clinmedicine.19-2-169 Eslam, S., Divyanshu, D., Jacqueline, P., et al. (2018). Area postrema syndrome: frequency, criteria, and severity in AQP4-IgG-positive NMOSD. Neurology, 91, e1642–e1651. https://doi.org/10.1212/WNL.0000000000006392 Camara-Lemarroy, C. R., Abo Al Sahm, D., Boyko, M., et al. (2019, July). Area Postrema Syndrome. Neurohospitalist, 9(3), 174–175. https://doi.org/10.1177/1941874418809879 Wang, X., Shi, Z., Zhao, Z., et al. (2022, September 29). The causal relationship between neuromyelitis optica spectrum disorder and other autoimmune diseases. Front Immunol, 13, 959469. https://doi.org/10.3389/fimmu.2022.959469 Carnero Contentti, E., Okuda, D. T., Rojas, J. I., et al. (2023, September-October). MRI to differentiate multiple sclerosis, neuromyelitis optica, and myelin oligodendrocyte glycoprotein antibody disease. J Neuroimaging, 33(5), 688–702. https://doi.org/10.1111/jon.13137 Sultana, N., Jabeen, S., Rima, S., et al. (2023, July). Magnetic Resonance Imaging Evaluation of Common Spinal Intramedullary Tumours: Ependymoma and Astrocytoma. Mymensingh Med J, 32(3), 749–756. PMID: 37391969. Renaldo, F., Chalard, F., Valence, S., et al. (2021, September 14). Area Postrema Syndrome as the Initial Presentation of Alexander Disease. Neurology, 97(11), 548–549. https://doi.org/10.1212/WNL.0000000000012462 Additional Declarations No competing interests reported. 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-4225506","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":289712948,"identity":"94ec2118-fac7-4896-acc4-9d42afe9654a","order_by":0,"name":"Jing Li","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAyUlEQVRIiWNgGAWjYBACA2Yog42B+cCBDz9I08KWeHBmDzFaEEwe48McbERoMWfnPfyat+1OYp90z4fDDDwM8vxiB/BrsWzmS7PmbXtmzCZzdsPhAgsGw5mzEwg47DCPmTFv22E5NoncDYdn8DAkGNwmUgsPm0TOAyBJnBbjxxBbchiI02LZzGPGOOfcYWM2iTQDYCBLEPaLOf8Z4w9vyg4nzp+R/PjDhx828vzSBLQAAZsUD4IjQVA5CDB/JCaZjIJRMApGwQgGAIzTQN0Em+a3AAAAAElFTkSuQmCC","orcid":"","institution":"The Fourth Medical Center of PLA General Hospital","correspondingAuthor":true,"prefix":"","firstName":"Jing","middleName":"","lastName":"Li","suffix":""},{"id":289712950,"identity":"9d02c3c4-b379-4c56-884d-d2745f6236e1","order_by":1,"name":"yan yang","email":"","orcid":"","institution":"The Fourth Medical Center of PLA General Hospital","correspondingAuthor":false,"prefix":"","firstName":"yan","middleName":"","lastName":"yang","suffix":""},{"id":289712953,"identity":"7d3af207-0a53-4471-a2ce-a530d9cc12dc","order_by":2,"name":"ya Hu","email":"","orcid":"","institution":"The Fourth Medical Center of PLA General Hospital","correspondingAuthor":false,"prefix":"","firstName":"ya","middleName":"","lastName":"Hu","suffix":""},{"id":289712955,"identity":"5242380f-d31a-4599-bf34-c1658fddbc61","order_by":3,"name":"xiangdong Jia","email":"","orcid":"","institution":"The Fourth Medical Center of PLA General Hospital","correspondingAuthor":false,"prefix":"","firstName":"xiangdong","middleName":"","lastName":"Jia","suffix":""},{"id":289712957,"identity":"eb0c1299-db1b-4755-b6d3-ed0bdccd517d","order_by":4,"name":"junling ge","email":"","orcid":"","institution":"The Fourth Medical Center of PLA General Hospital","correspondingAuthor":false,"prefix":"","firstName":"junling","middleName":"","lastName":"ge","suffix":""},{"id":289712960,"identity":"d1a234dc-c7fc-43f0-bd4a-ea6e486106e9","order_by":5,"name":"guoen yao","email":"","orcid":"","institution":"The Fourth Medical Center of PLA General Hospital","correspondingAuthor":false,"prefix":"","firstName":"guoen","middleName":"","lastName":"yao","suffix":""}],"badges":[],"createdAt":"2024-04-06 03:44:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4225506/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4225506/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":54519005,"identity":"c8e3bb56-28b7-4a9a-8653-b5532fcbe98e","added_by":"auto","created_at":"2024-04-11 17:35:34","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":245304,"visible":true,"origin":"","legend":"\u003cp\u003eFigure displays the cranial imaging characteristics of Case 1. The T1 and T2 sequences show a clear localized lesion, with contrast-enhanced magnetic resonance imaging (MRI) indicating heterogeneous enhancement in the targeted area. Importantly, the diffusion-weighted imaging (DWI) sequence reveals no evident indications of cellular edema.\u003c/p\u003e","description":"","filename":"Fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4225506/v1/1736cb641b1995f8592dc8a4.jpg"},{"id":54519001,"identity":"0a9e0161-28b1-41b6-8212-e5000fbcafae","added_by":"auto","created_at":"2024-04-11 17:35:34","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":386166,"visible":true,"origin":"","legend":"\u003cp\u003eFigure presents a hematoxylin and eosin (H\u0026amp;E) stained image of brain tissue from Case 1, observed under an Olympus light microscope at 100x magnification. It clearly shows significant hemorrhage within the brain tissue, alongside dysplastic proliferation of glial cells, which are arranged in a complex interwoven pattern.\u003c/p\u003e","description":"","filename":"Fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4225506/v1/8cff539cff22082fbee26480.jpg"},{"id":54519003,"identity":"50181b0b-4de3-4452-af28-555906418f3c","added_by":"auto","created_at":"2024-04-11 17:35:34","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":487727,"visible":true,"origin":"","legend":"\u003cp\u003eFigure displays the results of immunohistochemical staining on the pathological specimen from Case 1, captured under an Olympus light microscope at 100x magnification. The immunohistochemical analysis shows the following marker expressions: cytokeratin (CK) (negative), epithelial membrane antigen (EMA) (negative), vimentin (Vim) (positive), glial fibrillary acidic protein (GFAP) (strongly positive), S-100 protein (positive), oligodendrocyte transcription factor 2 (Olig2) (negative), neuronal nuclei (NeuN) (negative), and a Ki-67 proliferation index of 5%. These results support the diagnosis of a Grade II astrocytoma according to the World Health Organization (WHO) classification.\u003c/p\u003e","description":"","filename":"Fig3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4225506/v1/49825f13c8749e0cc1637a47.jpg"},{"id":54519004,"identity":"c3178b86-c219-423b-b1ea-b60e6cb9cf6b","added_by":"auto","created_at":"2024-04-11 17:35:34","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":139458,"visible":true,"origin":"","legend":"\u003cp\u003eFigure illustrates the cranial imaging features of Case 2. Panel A, using a sagittal T2 sequence, shows clear pathological findings in the Area Postrema and notable demyelination changes extending longitudinally along the spinal cord. Panel B, through a FLAIR sequence, accentuates the pathological alterations in the posterior region.\u003c/p\u003e","description":"","filename":"fig4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4225506/v1/5ea81c7f58e0f3a3eaf120bf.jpg"},{"id":56910941,"identity":"5a243528-767d-4b01-b9a2-fe7d39262513","added_by":"auto","created_at":"2024-05-22 05:01:28","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1583622,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4225506/v1/320000ea-e491-448b-9805-81645a390b5e.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Unraveling the Complexity of Area Postrema Lesions: Insights from Neuromyelitis Optica Spectrum Disorder and Beyond","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe area postrema, located at the caudal end of the fourth ventricle within the medulla oblongata, is a bilaterally symmetrical structure reminiscent of a leaf. Situated above the vagal triangle, it shares a close association with the nucleus tractus solitarius \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. Characterized by its highly vascular and loosely arranged tissue, the area postrema is notable for its absence of the blood-brain barrier. This feature renders it a critical sensor for hydrophilic compounds that struggle to permeate the blood-brain barrier to access the cerebrospinal fluid (CSF) \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. Together with the nucleus of the solitary tract and the dorsal motor nucleus of the vagus nerve, it constitutes the Dorsal Vagal Complex (DVC) \u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. The DVC plays a pivotal role in managing nausea, vomiting, and hiccupping, in addition to its involvement in eating, metabolism, cardiovascular regulation, and the equilibrium of fluid and CSF \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eArea Postrema Syndrome (APS) manifests through persistent, challenging-to-manage symptoms of nausea, retching, and vomiting persisting for a minimum of 48 hours. APS can present in various forms, including acute, subacute, periodic, or chronic. A definitive diagnosis necessitates the exclusion of other possible causes. Notably, APS may signal the presence of neuromyelitis optica spectrum disorders (NMOSD) due to neuroinflammatory processes within this region \u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. While APS may arise from non-demyelinating lesions, its association with NMOSD is critical for accurate diagnosis and prognosis, often indicating a more adverse outcome for individuals with NMOSD \u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe clinical presentation of APS, chiefly distinguished by relentless and difficult-to-manage nausea and vomiting, complicates diagnosis due to their resemblance to symptoms of gastrointestinal, metabolic, biochemical, and psychiatric conditions \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. Consequently, patients with APS frequently encounter a broad spectrum of medical specialties beyond neurology \u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. Delays in recognizing APS-NMOSD can lead to dire outcomes, including acute myelitis, optic neuritis, or brainstem lesions, potentially resulting in permanent neurological deficits \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. In extreme cases, it may precipitate respiratory failure and sudden cardiac arrest, occasionally without prior warning \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe complex nature and varied presentations of APS underscore the necessity for its swift identification and the implementation of effective treatment strategies. This study delves into two particular cases of APS, one associated with NMOSD and the other with medullary astrocytoma. These cases contribute valuable insights into the pathophysiological mechanisms and clinical manifestations of APS, highlighting the critical need for prompt and accurate diagnosis.\u003c/p\u003e"},{"header":"CASE REPORT","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eCASE 1\u003c/h2\u003e \u003cp\u003eA 57-year-old male was admitted to the hospital following the sudden and prolonged emergence of nausea and vomiting, which had persisted for three months. Additionally, he reported experiencing dizziness over the last two weeks. Before hospitalization, the patient had suffered from nausea, vomiting, hiccups, and exacerbated hypertension upon standing. Gastric endoscopy uncovered superficial gastritis and cholecystitis. The patient's symptoms showed limited response to oral interventions, including antihypertensive medications that managed the hypotension effectively but failed to significantly alleviate the gastrointestinal distress. The patient also described feelings of instability while standing and intermittent episodes of lightheadedness.\u003c/p\u003e \u003cp\u003eDiagnostic imaging via a head MRI revealed an anomalous mass in the dorsal medulla oblongata. Physical examination indicated asymmetry in the uvula's size and shape, with a pronounced shift to the left. Furthermore, muscle mass loss was noted on the left side of the tongue, causing the tongue to deviate leftward. No signs of meningeal engagement were present. The mass was diagnosed as a WHO Grade II astrocytoma, characterized in MRI scans as a slightly elongated, well-demarcated lesion in the posterior medullary region. The lesion exhibited uniform enhancement, discernible in both T1 and T2 weighted images. Measuring 1.2 cm, the lesion compressed the central canal of the fourth ventricle without displaying abnormal enhancement post-Gd-DTPA injection (refer to Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Pathological examination confirmed the diagnosis of Grade II astrocytoma (refer to Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eCASE 2\u003c/h3\u003e\n\u003cp\u003eA 24-year-old woman was admitted to our hospital with a 20-month history of daily hiccups and vomiting. Gastroscopy identified chronic non-atrophic gastritis, yet treatments failed to alleviate her symptoms. Approximately 18 months prior to this visit, she began experiencing a decline in vision. Diagnostic evaluations revealed positivity for AQP-4 antibodies and negativity for MOG antibodies, along with anti-SSB, anti-SSA/60KD, and anti-SSA/52KD antibodies, indicating Sj\u0026ouml;gren's syndrome. An initial head MRI detected posterior cerebral lesions. Treatment with pulse therapy, comprising methylprednisolone, azathioprine, and cyclophosphamide, led to symptom alleviation.\u003c/p\u003e \u003cp\u003eHowever, ten days before her current admission, the patient developed new symptoms: fecal incontinence, coughing and choking while drinking water, and numbness and weakness in her limbs. These symptoms emerged after she had discontinued her medication two months earlier. A follow-up cranial MRI reconfirmed lesions in the brain's posterior region, and similar pulse therapy yielded symptom improvement. The onset of these symptoms followed a period during which she had ceased her medication, leading to generalized itching, continuous hiccups, reduced appetite, constipation, urination difficulties, abdominal bloating, and coughing upon liquid intake, along with numbness and thermal sensation loss in her limbs.\u003c/p\u003e \u003cp\u003eThe patient's personal, marital, and family medical histories were unremarkable. Neurological examination at admission showed decreased visual acuity in both eyes, a delayed pharyngeal reflex, reduced muscle strength in all limbs, sensory impairments below the T4 level, and left-sided pathological signs. Extensive MRI imaging of the head and neck revealed abnormal posterior brain signals and segmental demyelination in the cervical cord (refer to Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). The patient underwent pulse therapy with steroids and azathioprine, alongside symptomatic care including enemas and interventions to aid bowel movement, resulting in gradual symptom improvement.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe area postrema, a region within the brain characterized by its high vascularization, features sinusoidal capillaries with pores alongside diverse cell types, including ependymal cells, glial cells, and small neurons. This region stands out from adjacent white matter areas due to its increased surface area, elevated plasma flow, and enhanced permeability \u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. The reduced velocity of blood flow facilitates extended transport times for blood-borne signaling molecules and toxins, thereby amplifying the exposure of local neurons and glial cells to blood-derived components. Such characteristics afford the area postrema a significant role in receptor-mediated interactions, essential for internal homeostasis and fluid regulation \u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. Despite its crucial functions, the diminutive and intricate structure of the area postrema complicates research efforts, prompting continued discourse regarding its exact roles \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. Lesions within this area commonly manifest as persistent nausea, vomiting, and hiccupping \u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\n\u003ch3\u003eNMOSD and APS\u003c/h3\u003e\n\u003cp\u003eNeuromyelitis Optica Spectrum Disorder (NMOSD) is defined by inflammation and degradation of the myelin sheath enveloping nerve fibers in the central nervous system. It is noteworthy that Area Postrema Syndrome (APS) constitutes one of the six principal symptoms indicative of NMOSD \u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. NMOSD's development is linked to the presence of autoantibodies targeting aquaporin-4 (AQP4), which can penetrate the blood-brain barrier and instigate astrocyte destruction via complement system activation \u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. Given the abundant distribution of AQP4 throughout the nervous system, especially in the area postrema, this region is particularly vulnerable to NMOSD \u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe prevalence of isolated APS among NMOSD patients ranges from 7.1\u0026ndash;10.3%. Conversely, APS presenting alongside other neurological manifestations is reported in 9.4\u0026ndash;15.9% of cases, underscoring its rarity as a disease manifestation \u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. Typically, patients display one to three symptoms, with vomiting being the most common, followed by hiccupping \u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. Nausea usually emerges abruptly, vomiting may be sporadic or persistent, often triggered by ingestion, and hiccupping tends to be protracted \u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. The clinical trajectory of APS varies, with nausea enduring for a median of 14 days, vomiting averaging five episodes per day, and hiccupping lasting a median of 14 days \u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. These symptoms frequently precede optic neuritis or transverse myelitis, marking early indications of NMOSD \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. In our second case, the patient reported enduring, episodic hiccupping and vomiting over two months, showing improvement post steroid and gamma-globulin therapy administration. Nonetheless, detailed data on the specific characteristics and frequency of these episodes remain scarce, largely due to the difficulty patients and their families face in accurately recalling them.\u003c/p\u003e \u003cp\u003ePathologically, NMOSD-associated posterior lesions are characterized by disorganized tissue, thickened vascular walls, and infiltration by activated immune cells, leading to glial cell destruction and neuronal activation, manifesting as nausea and vomiting [6]. The potential reversibility of posterior lesions in NMOSD hints at the transient impairment of astrocyte function [6]. In our second case, the patient presented with persistent posterior medullary lesions on imaging during their hospital stay, suggesting either the partial persistence of the initial lesion, resulting in ongoing damage, or the development of new lesions, as evidenced by the reappearance of posterior medullary symptoms on the second visit. Consequently, while NMOSD lesions may exhibit a degree of reversibility, some residual damage may persist, indicating a partial reversibility of NMOSD-associated posterior lesions.\u003c/p\u003e\n\u003ch3\u003eDistinguishing Astrocytoma from NMOSD in APS Patients\u003c/h3\u003e\n\u003cp\u003eAstrocytoma is characterized by an aberrant proliferation of glial cells within the area postrema, where these cells multiply more rapidly than normal, often portending a poor prognosis for the patient. Conversely, neuromyelitis optica spectrum disorder (NMOSD) stems from an autoimmune dysfunction, generally presenting a more favorable prognosis than tumors. This distinction underscores the necessity of considering rare tumor disorders in the differential diagnosis of area postrema lesions. Furthermore, NMOSD frequently coexists with other autoimmune disorders, as illustrated in our second case, including Sj\u0026ouml;gren's syndrome, and may be associated with conditions such as rheumatoid arthritis, systemic lupus erythematosus, antiphospholipid syndrome, and autoimmune thyroid disease (AITD), affecting multiple body systems beyond the neurological sphere \u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eImaging distinctions reveal that NMOSD lesions typically exhibit clearer demarcations compared to tumor lesions. NMOSD can impact various brain regions, manifesting as patchy lesions adjacent to the ventricles, the corpus callosum, along the corticospinal tract, within the deep white matter, or as subcortical lesions \u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. NMOSD is characterized by subtle blood-brain barrier alterations leading to meningeal enhancement and is marked by linear ependymal surface enhancement, akin to pencil-like lesions \u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. The \u0026ldquo;linear stripe sign\u0026rdquo; in sagittal MRI and the \u0026ldquo;inverted V sign\u0026rdquo; in horizontal T2 FLAIR sequences are highly specific for APS in NMOSD patients, although these imaging findings may also occur in other conditions \u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAstrocytomas present on imaging as irregular masses with vague boundaries, displaying isointense or hypointense signals on T1-weighted images and hyperintense signals on T2-weighted scans. These tumors may present as mixed, cystic, or solid masses, showing localized and irregular enhancement, particularly at the edges, upon Gd-DTPA-enhanced MRI \u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e. In our first case, the tumor manifested as a discrete mass with slight irregular contrast enhancement on enhanced brain MRI, aligning with prior documentation. Unlike systemic tumors, area postrema tumors typically remain localized. Patients with NMOSD may initially exhibit symptoms indicative of antiphospholipid syndrome (APS), emphasizing the importance of conducting additional diagnostic tests, such as serum aquaporin-4 (AQP-4) and myelin oligodendrocyte glycoprotein (MOG) measurements, to differentiate between these conditions.\u003c/p\u003e \u003cp\u003eTreatment modalities vary significantly between conditions. For astrocytomas, treatment may involve surgical excision and chemotherapy, tailored to individual tumor characteristics, as demonstrated in our first case, which resulted in a positive outcome post-surgery. NMOSD management includes a regimen of steroids, intravenous immunoglobulin, monoclonal antibodies, immunosuppressants, and symptomatic treatments, targeting the specific needs of various NMOSD presentations.\u003c/p\u003e\n\u003ch3\u003eOther Causes of APS\u003c/h3\u003e\n\u003cp\u003eArea Postrema Syndrome (APS) can result from autoimmune inflammatory conditions or various tumors located in the area postrema, such as neurocutaneous melanosis, choroid plexus tumors, pilocytic astrocytoma, or neuroenteric cysts \u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. The first case presented in this study is an example of a WHO Grade II pilocytic astrocytoma, a relatively rare occurrence. Additionally, APS may manifest as an initial symptom of other diseases, including lupus-related neuropathy, CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids), anti-GFAP encephalomyelitis, brainstem encephalitis, and secondary infectious myelitis, though it is uncommon in patients with multiple sclerosis or strokes \u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. APS is associated with a wide array of conditions ranging from autoimmune and inflammatory disorders to sudden infant death syndrome, Alexander disease, and radiation-induced nausea and vomiting, thereby broadening the spectrum of APS-related conditions \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eNeurologists face the critical task of distinguishing APS from Wernicke's encephalopathy during diagnosis. Despite the differences in etiology and treatment approaches, both conditions may present with similar features, including the affected brain regions, tissue structural changes, and clinical manifestations \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. A thorough evaluation is essential for the precise diagnosis and effective management of these conditions, underscoring the complexity and varied nature of APS and highlighting the need for a comprehensive understanding of its potential causes.\u003c/p\u003e\n\u003ch3\u003eClinical Diagnosis Suggestions and Recommendations for Cases\u003c/h3\u003e\n\u003cp\u003eLesions in the postrema region can manifest alongside various neurological symptoms, underscoring the need for an exhaustive neurological evaluation. Persistent symptoms such as prolonged nausea, vomiting, and hiccupping, despite targeted treatment, may indicate the presence of region postrema lesions. Beyond the commonly diagnosed Neuromyelitis Optica Spectrum Disorder (NMOSD), healthcare providers should consider a wide array of potential causes for these lesions. The tumor in our first case is particularly notable for its unusual location, even though the tumor type is relatively common. Regrettably, the tumor sample from the first patient was inadequate for comprehensive genetic analysis, limiting the examination to gross pathology and immunohistochemical studies.\u003c/p\u003e \u003cp\u003eInitially, the cases discussed presented with gastrointestinal symptoms, leading patients to seek care from gastroenterology specialists. This approach underscores the critical role of extensive diagnostic evaluations, including upper endoscopy, transit tests, and abdominal CT scans, for patients presenting with these symptoms. However, the emergence of additional neurological symptoms suggesting area postrema involvement often results in diagnostic and treatment delays \u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. This situation reinforces a key recommendation: medical professionals encountering patients with gastrointestinal complaints, especially nausea, vomiting, and hiccupping, should consider the potential for underlying neurological conditions. Employing a comprehensive diagnostic approach is essential in clinical practice to enhance cause identification, accelerate the diagnostic process, and ensure the provision of timely and appropriate treatment. Prompt assessment of neurological issues enables physicians to more effectively direct further examinations and treatments, laying the foundation for comprehensive and individualized healthcare delivery.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur investigation into the area postrema, particularly within the scope of neuromyelitis optica spectrum disease (NMOSD), underscores the critical need for heightened physician awareness regarding these conditions. Symptoms of area postrema syndrome, notably hiccups, nausea, and vomiting, are distinctive yet challenging to diagnose due to their similarity to gastrointestinal disorders.\u003c/p\u003e \u003cp\u003eThrough detailed examination of two cases, this study illuminates the varied etiologies affecting the posterior medullary region. The first case, involving a WHO Grade II astrocytoma, underlines the potential for tumor-induced symptoms to mimic those of gastrointestinal illnesses, accentuating the necessity for accurate diagnostic techniques. Conversely, the second case elucidates the intricate symptomatology associated with NMOSD, further complicated by concurrent Sj\u0026ouml;gren's syndrome, demanding an exhaustive and multidisciplinary diagnostic approach.\u003c/p\u003e \u003cp\u003eThese instances stress the imperative for medical professionals to consider a broad spectrum of differential diagnoses upon encountering symptoms indicative of area postrema involvement, mindful of the overlap between neurological and gastrointestinal manifestations. The high risk of misdiagnosis mandates a detailed and thorough evaluation of the posterior medullary region's anatomy and pathology.\u003c/p\u003e \u003cp\u003eIntegrating these insights into standard clinical practice is vital to averting diagnostic delays and ensuring the prompt delivery of appropriate treatments. The complex interplay between neurological and gastrointestinal symptoms in the posterior medullary region necessitates a more discerning and nuanced approach to diagnosis, ultimately enhancing care quality for individuals with area postrema syndrome in the context of NMOSD.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical Approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the institutional review board of The Fourth Medical Center of PLA General Hospital, following the principles outlined in the Declaration of Helsinki. The committee stressed the importance of obtaining participants\u0026apos; consent, informed consent, and consent for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJL, JLG, and GEY contributed to the conception of the study and clinical image analysis. JL and XDJ were involved in MR data acquisition. JL and YH handled clinical data acquisition. JL and YY are responsible for collecting pathology images. JL, JLG, and GEY contributed to interpretation and drafting, while JLG and GEY played crucial roles in revising for important intellectual content.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclaration of Conflicting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author(s) declared no potential conflicts of interest concerning the research, authorship, and/or publication of this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author(s) received no financial support for the research, authorship, and/or publication of this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of Data and Materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn alignment with the principles of transparency and scientific openness, all pertinent data and materials supporting the findings of this clinical case report are available upon reasonable request. Requests for data should be directed to Jing Li at [email protected].\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eZhang, C., Kaye, J. A., Cai, Z., et al. (2021). Area Postrema Cell Types that Mediate Nausea-Associated Behaviors. Neuron, 109(3), 461\u0026ndash;472.e5. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.neuron.2020.11.010\u003c/span\u003e\u003cspan address=\"10.1016/j.neuron.2020.11.010\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMirza, M., \u0026amp; Das, J. M. (2023, August 8). Neuroanatomy, Area Postrema. In StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. PMID: 31334969.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhou, C., Liao, L., Sun, R., et al. (2021). 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Neurology, 97(11), 548\u0026ndash;549. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1212/WNL.0000000000012462\u003c/span\u003e\u003cspan address=\"10.1212/WNL.0000000000012462\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":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":"area postrema, area postrema syndrome, Neuromyelitisoptica spectrumdisorders, WHO Grade II Astrocytoma","lastPublishedDoi":"10.21203/rs.3.rs-4225506/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4225506/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eLesions in the area postrema may lead to symptoms including hiccupping, nausea, and vomiting. Often termed area postrema syndrome, these symptoms are commonly linked to neuromyelitis optica spectrum disorders (NMOSD). This study analyzes two case studies to illustrate the varied clinical manifestations of area postrema lesions. The first case involves a 57-year-old male presenting with persistent symptoms of nausea, vomiting, and dizziness. Subsequent examination led to a diagnosis of WHO Grade II astrocytoma. The second case details a 24-year-old woman with hiccupping, deteriorating vision, incontinence, and limb numbness. She was subsequently diagnosed with concurrent neuromyelitis optica spectrum disorder (NMOSD) and Sj\u0026ouml;gren's syndrome. Importantly, the second case showed distinct gastrointestinal symptoms before treatment, leading to a crucial diagnosis of lesions in the posterior medullary region. These case studies highlight the risk of misdiagnosis and underscore the importance of quickly recognizing posterior medulla-related symptoms. A deep understanding of postrema lesions is essential for accurate diagnosis and prompt management. This underscores the need for a comprehensive clinical approach to enhance patient outcomes.\u003c/p\u003e","manuscriptTitle":"Unraveling the Complexity of Area Postrema Lesions: Insights from Neuromyelitis Optica Spectrum Disorder and Beyond","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-11 17:35:29","doi":"10.21203/rs.3.rs-4225506/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":"65bc4665-df72-49f1-94c3-c63ca5726531","owner":[],"postedDate":"April 11th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-05-22T04:53:21+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-11 17:35:29","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4225506","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4225506","identity":"rs-4225506","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}